Sample records for advanced treatment options

  1. The Effect of Solution Heat Treatment on an Advanced Nickel-Base Disk Alloy

    NASA Technical Reports Server (NTRS)

    Gayda, J.; Gabb, T. P.; Kantzos, P. T.

    2004-01-01

    Five heat treat options for an advanced nickel-base disk alloy, LSHR, have been investigated. These included two conventional solution heat treat cycles, subsolvus/oil quench and supersolvus/fan cool, which yield fine grain and coarse grain microstructure disks respectively, as well as three advanced dual microstructure heat treat (DMHT) options. The DMHT options produce disks with a fine grain bore and a coarse grain rim. Based on an overall evaluation of the mechanical property data, it was evident that the three DMHT options achieved a desirable balance of properties in comparison to the conventional solution heat treatments for the LSHR alloy. However, one of the DMHT options, SUB/DMHT, produced the best set of properties, largely based on dwell crack growth data. Further evaluation of the SUB/DMHT option in spin pit experiments on a generic disk shape demonstrated the advantages and reliability of a dual grain structure at the component level.

  2. Hyperhidrosis: review of recent advances and new therapeutic options for primary hyperhidrosis.

    PubMed

    Brown, Ashley L; Gordon, Jennifer; Hill, Samantha

    2014-08-01

    Primary focal hyperhidrosis is a common condition that negatively impacts quality of life for many pediatric patients and can be challenging to treat. Standard treatments for hyperhidrosis can be used with success in many patients, and newer therapies and techniques offer options that have demonstrated efficacy and safety. This review highlights standard therapies for primary focal hyperhidrosis as well as the most recent technique advancements and alternative treatment options. The standard approach to treating primary focal hyperhidrosis remains initiation of topical preparations, followed by advancement to systemic medications, local administration of medication and/or surgical procedures. Recent studies focus on enhancing tolerability of topical preparations as well as evaluating the efficacy of neuromodulator injections, oral anticholinergic medications and laser therapy. Microwave technology has also been introduced for the treatment of focal hyperhidrosis with promising results. Many therapies exist for hyperhidrosis, and each treatment plan must be evaluated on a patient-by-patient basis. Advances in standard therapies and emergence of new treatment techniques are the main emphases of current published literature on hyperhidrosis. This article presents recent therapeutic options as well as updates on more established strategies to help practitioners treat this challenging condition.

  3. The history and progression of treatments for allergic rhinitis.

    PubMed

    Ostrom, Nancy K

    2014-01-01

    This article intends to place new treatments in the context of allergic rhinitis (AR) treatment history. The medical literature was searched for significant advances and changes in AR treatment. Historical data on AR treatment options and management were selected. Reviews of AR management published throughout the 20th century were included to provide context for treatment advances. Modern AR treatment began in the early 20th century with immunotherapy and was soon followed by the emergence of antihistamine therapy in the 1930s. Numerous treatments for AR have been used over the ensuing decades, including decongestants, mast cell stabilizers, and leukotriene receptor antagonists. Topical corticosteroid options were developed the 1950s, and, added to baseline antihistamine therapy, became the foundation of AR treatment. Treatment options were significantly impacted after the 1987 Montreal Protocol, which phased out the use of chlorofluorocarbon propellant aerosols because of environmental concerns. From the mid-1990s until recently, this left only aqueous solution options for intranasal corticosteroids (INSs). The approval of the first hydrofluoroalkane propellant aerosol INSs for AR in 2012 restored a "dry" aerosol treatment option. The first combination intranasal antihistamine/INSs was also approved in 2012, providing a novel treatment option for AR. Treatment of AR has progressed with new therapeutic options now available. This should continue to move forward with agents to alter the allergic mechanism itself and impact the disease burden that has a significant impact on patient outcomes.

  4. A Review and Update of Treatment Options and Controversies in the Management of Hepatocellular Carcinoma.

    PubMed

    Dhir, Mashaal; Melin, Alyson A; Douaiher, Jeffrey; Lin, Chi; Zhen, Weining Ken; Hussain, Shahid M; Geschwind, Jean-Francois H; Doyle, Maria B Majella; Abou-Alfa, Ghassan K; Are, Chandrakanth

    2016-06-01

    To review the current management, outline recent advances and address controversies in the management of hepatocellular carcinoma (HCC). The treatment of HCC is multidisciplinary involving hepatologists, surgeons, medical oncologists, radiation oncologists, radiologists, interventional radiologists, and other disciplines. Each of these disciplines brings its unique perspective and differing opinions that add to controversies in the management of HCC. A focused literature review was performed to identify recent studies on the management of HCC and thereby summarize relevant information on the various therapeutic modalities and controversies involved in the treatment of HCC. The main treatment algorithms continue to rely on hepatic resection or transplantation with controversies involving patients harboring early stage disease and borderline hepatic function. The other treatment strategies include locoregional therapies, radiation, and systemic therapy used alone or in combination with other treatment modalities. Recent advances in locoregional therapies, radiation, and systemic therapies have provided better therapeutic options with curative intent potential for some locoregional therapies. Further refinements in combination therapies such as algorithms consisting of locoregional therapies and systemic or radiation therapies are likely to add additional options and improve survival. The management of HCC has witnessed significant strides with advances in existing options and introduction of several new treatment modalities of various combinations. Further refinements in these treatment options combined with enrollment in clinical trials are essential to improve the management and outcomes of patients with HCC.

  5. Current Options and Emerging Biomaterials for Periprosthetic Joint Infection.

    PubMed

    Levack, Ashley E; Cyphert, Erika L; Bostrom, Mathias P; Hernandez, Christopher J; von Recum, Horst A; Carli, Alberto V

    2018-04-30

    Infection in the setting of total joint arthroplasty, referred to as periprosthetic joint infection (PJI), is a devastating complication requiring prolonged and costly treatment. The unique environment around an artificial joint and ability of surrounding tissues to sequester bacteria collectively make prevention, diagnosis, and treatment of this condition challenging. In light of the unique pathogenesis of PJI, this review explores the limitations of contemporary treatments and discusses novel treatment options. Recent advancements in local antibiotic delivery platforms for preventing and treating PJI include titanium nanotube arrays, synthetic polymers, resorbable hydrogels, and cyclodextrin-based drug delivery options. In particular, cyclodextrins have facilitated great advancements in other clinical disorders and have demonstrated early promise as a future option in the arena of PJI. Novel treatment modalities for PJI optimize the implant surfaces to prevent bacterial biofilm formation or provide prolonged intra-articular antibiotic dosing to eradicate bacteria.

  6. Cabozantinib for Initial Treatment of Kidney Cancer

    Cancer.gov

    FDA has approved cabozantinib (Cabometyx®) as an initial treatment for patients with advanced renal cell carcinoma. The approval adds another tyrosine kinase inhibitor to the available options for patients with advanced kidney cancer.

  7. Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial.

    PubMed

    Holodniy, Mark; Brown, Sheldon T; Cameron, D William; Kyriakides, Tassos C; Angus, Brian; Babiker, Abdel; Singer, Joel; Owens, Douglas K; Anis, Aslam; Goodall, Ruth; Hudson, Fleur; Piaseczny, Mirek; Russo, John; Schechter, Martin; Deyton, Lawrence; Darbyshire, Janet

    2011-03-31

    Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting. We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count≤300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (≤4 ARVs) or intensive (≥5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log(10) copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86-1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68-1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options. We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options. Clinicaltrials.gov NCT00050089.

  8. Results of Antiretroviral Treatment Interruption and Intensification in Advanced Multi-Drug Resistant HIV Infection from the OPTIMA Trial

    PubMed Central

    Holodniy, Mark; Brown, Sheldon T.; Cameron, D. William; Kyriakides, Tassos C.; Angus, Brian; Babiker, Abdel; Singer, Joel; Owens, Douglas K.; Anis, Aslam; Goodall, Ruth; Hudson, Fleur; Piaseczny, Mirek; Russo, John; Schechter, Martin; Deyton, Lawrence; Darbyshire, Janet

    2011-01-01

    Background Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting. Methods and Findings We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count ≤300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (≤4 ARVs) or intensive (≥5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log10 copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86–1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68–1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options. Conclusions We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options. Trial Registration Clinicaltrials.gov NCT00050089 PMID:21483491

  9. Current stage in inflammatory bowel disease: What is next?

    PubMed Central

    Gómez-Gómez, Gonzalo Jesús; Masedo, Ángeles; Yela, Carmen; Martínez-Montiel, Maria del Pilar; Casís, Begoña

    2015-01-01

    In recent years, the incidence of inflammatory bowel disease (IBD) has been on the rise, extending to countries where it was infrequent in the past. As a result, the gap between high and low incidence countries is decreasing. The disease, therefore, has an important economic impact on the healthcare system. Advances in recent years in pharmacogenetics and clinical pharmacology have allowed for the development of treatment strategies adjusted to the patient profile. Concurrently, new drugs aimed at inflammatory targets have been developed that may expand future treatment options. This review examines advances in the optimization of existing drug treatments and the development of novel treatment options for IBD. PMID:26525013

  10. Improving Decision Making for Feeding Options in Advanced Dementia: A Randomized, Controlled Trial

    PubMed Central

    Hanson, Laura C.; Carey, Timothy S.; Caprio, Anthony J.; Lee, Tae Joon; Ersek, Mary; Garrett, Joanne; Jackman, Anne; Gilliam, Robin; Wessell, Kathryn; Mitchell, Susan L.

    2011-01-01

    Background Feeding problems are common in dementia, and decision-makers have limited understanding of treatment options. Objectives To test whether a decision aid improves quality of decision-making about feeding options in advanced dementia. Design Cluster randomized controlled trial. Setting 24 nursing homes in North Carolina Participants Residents with advanced dementia and feeding problems and their surrogates. Intervention Intervention surrogates received an audio or print decision aid on feeding options in advanced dementia. Controls received usual care. Measurements Primary outcome was the Decisional Conflict Scale (range 1–5) measured at 3 months; other main outcomes were surrogate knowledge, frequency of communication with providers, and feeding treatment use. Results 256 residents and surrogate decision-makers were recruited. Residents’ average age was 85; 67% were Caucasian and 79% were women. Surrogates’ average age was 59; 67% were Caucasian, and 70% were residents’ children. The intervention improved knowledge scores (16.8 vs 15.1, p<0.001). After 3 months, intervention surrogates had lower Decisional Conflict Scale scores than controls (1.65 vs. 1.90, p<0.001) and more often discussed feeding options with a health care provider (46% vs. 33%, p=0.04). Residents in the intervention group were more likely to receive a dysphagia diet (89% vs.76%, p=0.04), and showed a trend toward increased staff eating assistance (20% vs.10%, p=0.08). Tube feeding was rare in both groups even after 9 months (1 intervention vs. 3 control, p=0.34). Limitations Cluster randomization was necessary to avoid contamination, but limits blinding and may introduce bias by site effect. Conclusion A decision aid about feeding options in advanced dementia reduced decisional conflict for surrogates and increased their knowledge and communication about feeding options with providers. PMID:22091750

  11. Cone beam volume tomography: an imaging option for diagnosis of complex mandibular third molar anatomical relationships.

    PubMed

    Danforth, Robert A; Peck, Jerry; Hall, Paul

    2003-11-01

    Complex impacted third molars present potential treatment complications and possible patient morbidity. Objectives of diagnostic imaging are to facilitate diagnosis, decision making, and enhance treatment outcomes. As cases become more complex, advanced multiplane imaging methods allowing for a 3-D view are more likely to meet these objectives than traditional 2-D radiography. Until recently, advanced imaging options were somewhat limited to standard film tomography or medical CT, but development of cone beam volume tomography (CBVT) multiplane 3-D imaging systems specifically for dental use now provides an alternative imaging option. Two cases were utilized to compare the role of CBVT to these other imaging options and to illustrate how multiplane visualization can assist the pretreatment evaluation and decision-making process for complex impacted mandibular third molar cases.

  12. Future Directions for Monitoring Treatment Response in Colorectal Cancer

    PubMed Central

    Walker, Avery S.; Zwintscher, Nathan P.; Johnson, Eric K.; Maykel, Justin A.; Stojadinovic, Alexander; Nissan, Aviram; Avital, Itzhak; Brücher, Björn LDM; Steele, Scott R.

    2014-01-01

    Treatment of advanced colon and rectal cancer has significantly evolved with the introduction of neoadjuvant chemoradiation therapy so much that, along with more effective chemotherapy regimens, surgery has been considered unnecessary among some institutions for select patients. The tumor response to these treatments has also improved and ultimately has been shown to have a direct effect on prognosis. Yet, the best way to monitor that response, whether clinically, radiologically, or with laboratory findings, remains controversial. The authors' aim is to briefly review the options available and, more importantly, examine emerging and future options to assist in monitoring treatment response in cases of locally advanced rectal cancer and metastatic colon cancer. PMID:24396497

  13. [Advanced and Metastatic Lung Cancer – What is new in the Diagnosis and Therapy?].

    PubMed

    Rothschild, Sacha I

    2015-07-01

    Lung cancer is one of the most common types of malignancies worldwide. The majority of patients are diagnosed with an incurable advanced/metastatic stage disease. Palliative treatment approaches improve the survival and the quality of life of these patients. Lung cancer is subdivided according to histology and molecular biology. The most important classification separates small cell from non-small cell lung cancer. In the subgroup of non-small cell lung cancer novel treatment approaches coming along with an improved prognosis have been established during the last decade. The current manuscript provides an overview on current treatment options for metastatic lung cancer. Furthermore, an outlook on promising future treatment options is provided.

  14. Antiangiogenic treatment in hepatocellular carcinoma: the balance of efficacy and safety

    PubMed Central

    Welker, Martin-Walter; Trojan, Joerg

    2013-01-01

    Hepatocellular carcinoma (HCC) is a severe complication of advanced liver disease with a worldwide incidence of more than 600,000 patients per year. Liver function, clinical performance status, and tumor size are considered in the Barcelona Clinic Liver Cancer (BCLC) system. While curative treatment options are available for early stages, most patients present with intermediate- or advanced-stage HCC, burdened with a poor prognosis, substantially influenced by the degree of liver-function impairment. Hypervascularization is a major characteristic of HCC, and antiangiogenic treatments are the basis of treatment in noncurative stages, including interventional and pharmacological treatments. Currently, the tyrosine-kinase inhibitor sorafenib is still the only approved drug for HCC. Further improvements in survival in patients with intermediate- and advanced-stage HCC may be anticipated by both multimodal approaches, such as combination of interventional and systemic treatments, and new systemic treatment options. Until now, the Phase III development of other tyrosine-kinase inhibitors in patients with advanced HCC has failed due to minor efficacy and/or increased toxicity compared to sorafenib. However, promising Phase II data have been reported with MET inhibitors in this hard-to-treat population. This review gives a critical overview of antiangiogenic drugs and strategies in intermediate- and advanced-stage HCC, with a special focus on safety. PMID:24204170

  15. Evidence-Based Medicine: Options for Dupuytren's Contracture: Incise, Excise, and Dissolve.

    PubMed

    Denkler, Keith A; Vaughn, Carolyn J; Dolan, Estelle L; Hansen, Scott L

    2017-01-01

    After studying this article, the participant should be able to: 1. Understand updates in the basic science, epidemiology, and treatment of Dupuytren's disease. 2. Understand treatment with needle aponeurotomy, collagenase, and fasciectomy. 3. Understand advanced needle techniques for Dupuytren's contracture. 4. Understand the safety and effectiveness of a new treatment, collagenase. The literature on Dupuytren's disease encompasses many specialties. Its treatment is generally by perforating, excising, or dissolving the affected tissues. This article reviews the changing understanding of this disease and treatment options.

  16. Current and future treatment options for esophageal cancer in the elderly.

    PubMed

    Bollschweiler, Elfriede; Plum, Patrick; Mönig, Stefan P; Hölscher, Arnulf H

    2017-07-01

    Esophageal cancer is the eighth most common cancer globally and has the sixth worst prognosis because of its aggressiveness and poor survival. Data regarding cancer treatment in older patients is limited because the elderly have been under-represented in clinical trials. Therefore, we reviewed the existing literature regarding treatment results for elderly patients (70+ years). Areas covered: We used pubmed to analyze the actual literature according to elderly esophageal cancer patients with subheading of incidence, esophagectomy, chemoradiation or chemotherapy. The main points of interest were treatment options for patients with Barrett's esophagus or early carcinoma, advanced tumor stages, and inoperable cancer. Expert opinion: The incidence of esophageal cancer has been increasing over the past thirty years, with a rapid increase of esophageal adenocarcinoma in Western industrialized nations. Patients aged over 60 years have been particularly affected. In this review, we have shown that elderly patients with esophageal cancer have various alternatives for adequate treatment. Clinical evaluation of comorbidity is necessary to make treatment decisions. Therapeutic options for early carcinomas are endoscopic or surgical resection. For elderly patients with advanced carcinomas, preoperative chemoradiation or chemotherapy should be discussed.

  17. Treatment of Parkinson's disease: a survey of patients and neurologists.

    PubMed

    Fargel, Matthias; Grobe, Bernd; Oesterle, Eberhard; Hastedt, Claudia; Rupp, Markus

    2007-01-01

    The treatment of Parkinson's disease (PD) is complex and highly individual. The choice between available treatment options depends on clinical characteristics such as the patient's age, disease severity and presence of comorbidities, lifestyle characteristics and preferences, costs of different medications and awareness and perception of available treatment options, and education of the treating physician. The impact of PD treatment regimens on patients' health-related quality of life (QOL) is also an important healthcare feature. The objective of the present study was to assess treatment options, treatment satisfaction and opinions about treatment improvements in patients with PD and neurologists treating the disease. Two surveys using face-to-face interviews and an additional phone survey were carried out in the US and five European countries (France, Germany, Italy, Spain and the UK). Patients with early and advanced stages of PD were included. To participate in the neurologist survey, neurologists were required to personally treat ten or more PD patients per month, including both early and advanced stage patients. Interviews consisted of a mix of closed and open-ended questions; some of these questions involved show cards. Of the 500 patients who were surveyed, 49% had early and 51% had advanced PD. Early-stage PD patients, both in the US and Europe, take a mean of 3.2 tablets daily of PD-medication. In contrast, the mean daily tablet load of PD medication is much higher for advanced-stage patients (9.9 and 8.4 tablets in the US and Europe, respectively). Tablet load was perceived as a major problem; the majority of patients wished to see improvements regarding daily medication intake and expressed interest in other delivery systems such as patches. Overall, patients rated their treatment with a score of 6.6 points (6.7 for early-stage and 6.6 for advanced-stage patients) [scale of 1-10; 10 being highest]. Physicians (n = 592) were satisfied with a number of current PD medications and assumed they improve the QOL of the patients. They regarded efficacy and safety as the most important features for the improvement of PD medication. Further research is needed into PD treatment options not only for symptom alleviation but for better delivery systems that could improve compliance and QOL for patients with PD. Treatment guidelines need to incorporate QOL aspects and general communication between the health professional and the patient.

  18. New therapeutic directions for advanced pancreatic cancer: cell cycle inhibitors, stromal modifiers and conjugated therapies.

    PubMed

    Matera, Robert; Saif, Muhammad Wasif

    2017-09-01

    Pancreatic adenocarcinoma is a devastating malignancy with an extremely poor prognosis. These tumors progress rapidly and somewhat silently with few specific symptoms and are relatively resistant to chemotherapeutic agents. Many agents, including cell cycle inhibitors, are under development for the treatment of this cancer for which there are disappointingly few treatment options. Areas covered: Here we outline the existing approved treatments for advanced pancreatic disease and discuss a range of novel therapies currently under development including cell cycle inhibitors, stromal modifiers and conjugated therapies. We also describe the current state of the pancreatic cancer therapeutics market both past and future. Expert opinion: Despite the recent explosion of novel therapies with an array of unique targets, the core treatment of pancreatic cancer still with traditional cytotoxic agents with a few exceptions. However, as these novel treatments move through the pipeline, we are hopeful that there will soon be a number of effective options for patients with advanced pancreatic cancer.

  19. Second-line treatments: moving towards an opportunity to improve survival in advanced gastric cancer?

    PubMed

    Salati, Massimiliano; Di Emidio, Katia; Tarantino, Vittoria; Cascinu, Stefano

    2017-01-01

    Gastric cancer is the third leading cause of cancer-related death globally with approximately 723 000 deaths every year. Most patients present with advanced unresectable or metastatic disease, only amenable to palliative systemic treatment and a median survival uncommonly exceeding 12 months. Over the last years, the efficacy of chemotherapy combination has plateaued and the introduction of the anti-human epidermal growth factor receptor 2 trastuzumab has resulted in a limited survival gain in the upfront setting. After this positive experience, first-line treatment with new targeted therapies failed to improve the outcome of advanced gastric cancer. On the contrary, second-line options, including monochemotherapy with taxanes or irinotecan and the anti-vascular endothelial growth factor receptor 2 ramucirumab, either alone or combined with paclitaxel, opened new therapeutic rooms for an ever-increasing number of patients who maintain an acceptable performance status across multiple lines. This article provides an updated overview on the current management of advanced gastric cancer and discusses how the different treatment options available may be best combined to favourably impact the outcome of patients following the logic of a treatment strategy.

  20. Second-line treatments: moving towards an opportunity to improve survival in advanced gastric cancer?

    PubMed Central

    Salati, Massimiliano; Di Emidio, Katia; Tarantino, Vittoria; Cascinu, Stefano

    2017-01-01

    Gastric cancer is the third leading cause of cancer-related death globally with approximately 723 000 deaths every year. Most patients present with advanced unresectable or metastatic disease, only amenable to palliative systemic treatment and a median survival uncommonly exceeding 12 months. Over the last years, the efficacy of chemotherapy combination has plateaued and the introduction of the anti-human epidermal growth factor receptor 2 trastuzumab has resulted in a limited survival gain in the upfront setting. After this positive experience, first-line treatment with new targeted therapies failed to improve the outcome of advanced gastric cancer. On the contrary, second-line options, including monochemotherapy with taxanes or irinotecan and the anti-vascular endothelial growth factor receptor 2 ramucirumab, either alone or combined with paclitaxel, opened new therapeutic rooms for an ever-increasing number of patients who maintain an acceptable performance status across multiple lines. This article provides an updated overview on the current management of advanced gastric cancer and discusses how the different treatment options available may be best combined to favourably impact the outcome of patients following the logic of a treatment strategy. PMID:29209523

  1. Esophageal Cancer Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Esophageal cancer treatment options include surgery alone for very early disease and add chemotherapy and radiation therapy for more advanced cases. Get detailed information about the treatment of newly diagnosed and recurrent esophageal cancer in this summary for clinicians.

  2. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms.

    PubMed

    Mooney, Michael A; Simon, Elias D; Little, Andrew S

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment.

  3. Treating Locally Advanced Cervical Cancer With Concurrent Chemoradiation Without Brachytherapy in Low-resource Countries.

    PubMed

    Chuang, Linus; Kanis, Margaux J; Miller, Brigitte; Wright, Jason; Small, William; Creasman, William

    2016-02-01

    To summarize the literature on options of management of patients treated for locally advanced cervical cancers with a specific focus on resource-constrained settings where brachytherapy is not available. A Medline search was performed to summarize studies about treatment approaches including neoadjuvant chemotherapy, primary surgery for bulky cervical cancer, and chemoradiation followed by surgery. Summaries are by treatment approaches that are relevant to resource-constrained settings. There are a lack of studies performed on neoadjuvant chemotherapy in low-resource settings. Primary surgery followed by chemoradiation therapy for selected patients with bulky cervical cancer is a feasible option. The disadvantage is the potential increase in treatment complications. Chemoradiation without brachytherapy followed by surgery has been found to have equivalent outcomes and is associated with acceptable morbidity. In resource-constrained settings where brachytherapy is not available, performing radical hysterectomy after chemoradiation therapy without brachytherapy has been shown to produce equivalent outcomes. It seems reasonable to adopt a modified therapeutic protocol of chemoradiation followed by extrafascial hysterectomy as an alternative treatment option in low-resource countries where brachytherapy is not readily available.

  4. Pollution loads in urban runoff and sanitary wastewater.

    PubMed

    Taebi, Amir; Droste, Ronald L

    2004-07-05

    While more attention has been paid in recent years to urban point source pollution control through the establishment of wastewater treatment plants in many developing countries, no considerable planning nor any serious measures have been taken to control urban non-point source pollution (urban stormwater runoff). The present study is a screening analysis to investigate the pollution loads in urban runoff compared to point source loads as a first prerequisite for planning and management of receiving water quality. To compare pollutant loads from point and non-point urban sources, the pollutant load is expressed as the weight of pollutant per hectare area per year (kg/ha.year). Unit loads were estimated in stormwater runoff, raw sanitary wastewater and secondary treatment effluents in Isfahan, Iran. Results indicate that the annual pollution load in urban runoff is lower than the annual pollution load in sanitary wastewater in areas with low precipitation but it is higher in areas with high precipitation. Two options, namely, advanced treatment (in lieu of secondary treatment) of sanitary wastewater and urban runoff quality control systems (such as detention ponds) were investigated as controlling systems for pollution discharges into receiving waters. The results revealed that for Isfahan, as a low precipitation urban area, advanced treatment is a more suitable option, but for high precipitation urban areas, urban surface runoff quality control installations were more effective for suspended solids and oxygen-demanding matter controls, and that advanced treatment is the more effective option for nutrient control.

  5. [Post-traumatic arthritis in the young patient : Treatment options before the endoprosthesis].

    PubMed

    Burkhart, K J; Hollinger, B

    2016-10-01

    In the young patient, treatment of post-traumatic elbow arthritis remains difficult. Total elbow arthroplasty must be delayed for as long as possible. Therapy starts with nonoperative treatment. If this fails, operative options can be discussed. The aim of surgery is to provide a functional range of motion with acceptable pain without obstructing future treatment options. Patients with pain at terminal extension and/or flexion may benefit from arthroscopic or open debridement. Patients with advanced osteoarthritis and pain throughout the complete range of motion, who are too young for total elbow arthroplasty, are offered interposition arthroplasty or arthrodesis. Arthrodesis of the elbow leads to significant restrictions in daily life due to the complete loss of extension/flexion. Therefore, arthrodesis is only offered as treatment in exceptional circumstances. Interposition arthroplasty is a reasonable option for the young patient without significant bony defects, which may provide a stable, functional flexion arc with an acceptable pain level. Interposition arthroplasty preserves the revision options of re-interposition arthroplasty as well as the withdrawal to total elbow arthroplasty. Partial and total elbow arthroplasty are treatment options of elbow arthritis but are not subjects of this article.

  6. Apatinib: A Review in Advanced Gastric Cancer and Other Advanced Cancers.

    PubMed

    Scott, Lesley J

    2018-05-01

    Apatinib [Aitan ® (brand name in China)], also known as rivoceranib, is a novel, small molecule, selective vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor and is the second anti-angiogenic drug to be approved in China for the treatment of advanced or metastatic gastric cancer. This article summarizes the pharmacological properties of apatinib and reviews its clinical use in chemotherapy-experienced patients with advanced gastric adenocarcinoma, including gastroesophageal adenocarcinoma (GEA), or with other advanced cancers such as non-small cell lung cancer (NSCLC), breast cancer, gynaecological cancers, hepatocellular carcinoma (HCC), thyroid cancer and sarcomas. As third- or subsequent-line therapy, oral apatinib significantly prolonged median progression-free survival (PFS) and overall survival (OS) compared with placebo and had a manageable safety profile in Chinese patients with advanced or metastatic gastric cancer or GEA participating in randomized, double-blind, multicentre, phase 2 and 3 trials. More limited evidence also supports it use as subsequent-line treatment in Chinese patients with other advanced or metastatic solid tumours, including NSCLC, breast cancer and HCC. Further clinical experience and long-term pharmacovigilance data are required to more definitively establish the efficacy and safety profile of apatinib, including its use in combination with other chemotherapy agents and its role in the management of other types of advanced or metastatic solid tumours. In the meantime, given its convenient administration regimen and the limited treatment options and poor prognosis for patients with advanced or metastatic solid tumours, apatinib is an important, emerging treatment option for adult patients with advanced gastric adenocarcinoma or GEA who have progressed or relapsed after chemotherapy.

  7. Clinically Applicable Inhibitors Impacting Genome Stability.

    PubMed

    Prakash, Anu; Garcia-Moreno, Juan F; Brown, James A L; Bourke, Emer

    2018-05-13

    Advances in technology have facilitated the molecular profiling (genomic and transcriptomic) of tumours, and has led to improved stratification of patients and the individualisation of treatment regimes. To fully realize the potential of truly personalised treatment options, we need targeted therapies that precisely disrupt the compensatory pathways identified by profiling which allow tumours to survive or gain resistance to treatments. Here, we discuss recent advances in novel therapies that impact the genome (chromosomes and chromatin), pathways targeted and the stage of the pathways targeted. The current state of research will be discussed, with a focus on compounds that have advanced into trials (clinical and pre-clinical). We will discuss inhibitors of specific DNA damage responses and other genome stability pathways, including those in development, which are likely to synergistically combine with current therapeutic options. Tumour profiling data, combined with the knowledge of new treatments that affect the regulation of essential tumour signalling pathways, is revealing fundamental insights into cancer progression and resistance mechanisms. This is the forefront of the next evolution of advanced oncology medicine that will ultimately lead to improved survival and may, one day, result in many cancers becoming chronic conditions, rather than fatal diseases.

  8. Current status in the treatment options for esophageal achalasia

    PubMed Central

    Chuah, Seng-Kee; Chiu, Chien-Hua; Tai, Wei-Chen; Lee, Jyong-Hong; Lu, Hung-I; Changchien, Chi-Sin; Tseng, Ping-Huei; Wu, Keng-Liang

    2013-01-01

    Recent advances in the treatment of achalasia include the use of high-resolution manometry to predict the outcome of patients and the introduction of peroral endoscopic myotomy (POEM). The first multicenter randomized, controlled, 2-year follow-up study conducted by the European Achalasia Trial group indicated that laparoscopic Heller myotomy (LHM) was not superior to pneumatic dilations (PD). Publications on the long-term success of laparoscopic surgery continue to emerge. In addition, laparoscopic single-site surgery is applicable to advanced laparoscopic operations such as LHM and anterior fundoplication. The optimal treatment option is an ongoing matter of debate. In this review, we provide an update of the current progress in the treatment of esophageal achalasia. Unless new conclusive data prove otherwise, LHM is considered the most durable treatment for achalasia at the expense of increased reflux-associated complications. However, PD is the first choice for non-surgical treatment and is more cost-effective. Repeated PD according to an “on-demand” strategy based on symptom recurrence can achieve long-term remission. Decision making should be based on clinical evidence that identifies a subcategory of patients who would benefit from specific treatment options. POEM has shown promise but its long-term efficacy and safety need to be assessed further. PMID:24023484

  9. Current status in the treatment options for esophageal achalasia.

    PubMed

    Chuah, Seng-Kee; Chiu, Chien-Hua; Tai, Wei-Chen; Lee, Jyong-Hong; Lu, Hung-I; Changchien, Chi-Sin; Tseng, Ping-Huei; Wu, Keng-Liang

    2013-09-07

    Recent advances in the treatment of achalasia include the use of high-resolution manometry to predict the outcome of patients and the introduction of peroral endoscopic myotomy (POEM). The first multicenter randomized, controlled, 2-year follow-up study conducted by the European Achalasia Trial group indicated that laparoscopic Heller myotomy (LHM) was not superior to pneumatic dilations (PD). Publications on the long-term success of laparoscopic surgery continue to emerge. In addition, laparoscopic single-site surgery is applicable to advanced laparoscopic operations such as LHM and anterior fundoplication. The optimal treatment option is an ongoing matter of debate. In this review, we provide an update of the current progress in the treatment of esophageal achalasia. Unless new conclusive data prove otherwise, LHM is considered the most durable treatment for achalasia at the expense of increased reflux-associated complications. However, PD is the first choice for non-surgical treatment and is more cost-effective. Repeated PD according to an "on-demand" strategy based on symptom recurrence can achieve long-term remission. Decision making should be based on clinical evidence that identifies a subcategory of patients who would benefit from specific treatment options. POEM has shown promise but its long-term efficacy and safety need to be assessed further.

  10. Use of androgen deprivation therapy in prostate cancer: indications and prevalence

    PubMed Central

    Connolly, Roisin M; Carducci, Michael A; Antonarakis, Emmanuel S

    2012-01-01

    Androgens play a prominent role in the development, maintenance and progression of prostate cancer. The introduction of androgen deprivation therapies into the treatment paradigm for prostate cancer patients has resulted in a wide variety of benefits ranging from a survival advantage for those with clinically localized or locally advanced disease, to improvements in symptom control for patients with advanced disease. Controversies remain, however, surrounding the optimal timing, duration and schedule of these hormonal approaches. Newer hormonal manipulations such as abiraterone acetate have also been investigated and will broaden treatment options for men with prostate cancer. This review highlights the various androgen-directed treatment options available to men with prostate cancer, their specific indications and the evidence supporting each approach, as well as patterns of use of hormonal therapies. PMID:22231299

  11. Updates in the Management of Hepatocellular Carcinoma

    PubMed Central

    Frenette, Catherine

    2011-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, and its increasing incidence worldwide is a cause for concern. Fortunately, advances in diagnostic and therapeutic approaches have contributed to earlier detection and treatment. As cancer epidemiology studies continue to elucidate the natural history of liver diseases, greater understanding of HCC has led to improved risk stratification and earlier enrollment of high-risk patients in cancer screening and surveillance programs. Improved survival rates among HCC patients also reflect significant advances in available treatment options. Advances in surgical techniques are pushing the boundaries of resection for localized disease, and progress in the field of transplantation has led to refinements in listing criteria and improved post-transplantation outcomes. The evolving field of locoregional therapies—including percutaneous ablation and transarterial chemoembolization—continues to provide novel therapeutic options that can be used in place of, or in addition to, surgical approaches. Recent advances in systemic multikinase inhibitor therapies have also demonstrated significant benefits for advanced-stage disease, and these therapies also show promise as adjuvant treatments for earlier-stage disease. This article provides an update on the management of HCC, with a focus on revised guidelines for screening and an in-depth discussion of emerging novel therapies. PMID:21346848

  12. Potentiality of immunotherapy against hepatocellular carcinoma

    PubMed Central

    Tsuchiya, Nobuhiro; Sawada, Yu; Endo, Itaru; Uemura, Yasushi; Nakatsura, Tetsuya

    2015-01-01

    Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the fifth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options remain limited for advanced HCC, and as a result prognosis continues to be poor. Current therapeutic options, surgery, chemotherapy and radiotherapy, have only modest efficacy. New treatment modalities to prolong survival and to minimize the risk of adverse response are desperately needed for patients with advanced HCC. Tumor immunotherapy is a promising, novel treatment strategy that may lead to improvements in both treatment-associated toxicity and outcome. The strategies have developed in part through genomic studies that have yielded candidate target molecules and in part through basic biology studies that have defined the pathways and cell types regulating immune response. Here, we summarize the various types of HCC immunotherapy and argue that the newfound field of HCC immunotherapy might provide critical advantages in the effort to improve prognosis of patients with advanced HCC. Already several immunotherapies, such as tumor-associated antigen therapy, immune checkpoint inhibitors and cell transfer immunotherapy, have demonstrated safety and feasibility in HCC patients. Unfortunately, immunotherapy currently has low efficacy in advanced stage HCC patients; overcoming this challenge will place immunotherapy at the forefront of HCC treatment, possibly in the near future. PMID:26420958

  13. Potentiality of immunotherapy against hepatocellular carcinoma.

    PubMed

    Tsuchiya, Nobuhiro; Sawada, Yu; Endo, Itaru; Uemura, Yasushi; Nakatsura, Tetsuya

    2015-09-28

    Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the fifth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options remain limited for advanced HCC, and as a result prognosis continues to be poor. Current therapeutic options, surgery, chemotherapy and radiotherapy, have only modest efficacy. New treatment modalities to prolong survival and to minimize the risk of adverse response are desperately needed for patients with advanced HCC. Tumor immunotherapy is a promising, novel treatment strategy that may lead to improvements in both treatment-associated toxicity and outcome. The strategies have developed in part through genomic studies that have yielded candidate target molecules and in part through basic biology studies that have defined the pathways and cell types regulating immune response. Here, we summarize the various types of HCC immunotherapy and argue that the new-found field of HCC immunotherapy might provide critical advantages in the effort to improve prognosis of patients with advanced HCC. Already several immunotherapies, such as tumor-associated antigen therapy, immune checkpoint inhibitors and cell transfer immunotherapy, have demonstrated safety and feasibility in HCC patients. Unfortunately, immunotherapy currently has low efficacy in advanced stage HCC patients; overcoming this challenge will place immunotherapy at the forefront of HCC treatment, possibly in the near future.

  14. Emerging treatments in alopecia.

    PubMed

    Falto-Aizpurua, Leyre; Choudhary, Sonal; Tosti, Antonella

    2014-12-01

    Alopecia is a common concern encountered in the medical practice. Treatment approach varies according to the type and severity of alopecia. However, available treatment options have limited efficacy and several adverse effects. Presently, there are different treatment options being studied to overcome these limitations. Additionally, cellular pathways involved in the pathophysiology of alopecia are further being clarified to potentially target pathogenic molecules. We searched the literature for recently published articles discussing new treatment options as well as mechanisms involved in alopecia. We discuss the use of stem cells, growth factors, cellular pathways and robotic hair transplant, among other emerging therapies used for alopecia. Future looks very promising and new effective treatments such as janus kinase inhibitors could possibly be available for alopecia areata. The stem-cell technology is advancing and companies involved in hair follicle neogenesis are starting clinical trials on patients with androgenetic alopecia.

  15. Re-Evaluating Progression in an Era of Progress: A Review of First- and Second-Line Treatment Options in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer.

    PubMed

    Castellanos, Emily H; Horn, Leora

    2016-06-01

    : The advent of crizotinib, the first small molecule inhibitor against anaplastic lymphoma kinase (ALK), has led to impressive advances in the care of patients with advanced ALK-rearranged non-small cell lung cancer. The development of second-generation ALK inhibitors, starting with the recent U.S. Food and Drug Administration approval of ceritinib, promises to expand the therapeutic landscape for this cohort of patients. With increasing use of molecularly targeted therapy options, it has been observed that disease progression in patients receiving targeted agents has a heterogeneous biology, manifesting as either oligoprogressive or widely progressive disease, which may require development of innovative treatment strategies. This review discusses the first- and second-generation ALK inhibitors approved or in clinical development, as well as the novel challenges and approaches to disease progression in patients on targeted agents. The identification of driver mutations in non-small cell lung cancer (NSCLC), most prominently epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), has expanded treatment options for a significant cohort of patients. However, the success of targeted agents has brought new challenges, particularly regarding management of progression. Progression manifests heterogeneously, and management of oligoprogression may differ from diffusely progressive disease. Multiple options for treatment at progression exist, and it is becoming evident that selecting the best avenue of care requires understanding the biology and potential drivers of disease progression. This review discusses the array of treatment options available for patients with ALK-positive NSCLC, as well as evaluation and treatment of progressive disease. ©AlphaMed Press.

  16. Re-Evaluating Progression in an Era of Progress: A Review of First- and Second-Line Treatment Options in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer

    PubMed Central

    Castellanos, Emily H.

    2016-01-01

    The advent of crizotinib, the first small molecule inhibitor against anaplastic lymphoma kinase (ALK), has led to impressive advances in the care of patients with advanced ALK-rearranged non-small cell lung cancer. The development of second-generation ALK inhibitors, starting with the recent U.S. Food and Drug Administration approval of ceritinib, promises to expand the therapeutic landscape for this cohort of patients. With increasing use of molecularly targeted therapy options, it has been observed that disease progression in patients receiving targeted agents has a heterogeneous biology, manifesting as either oligoprogressive or widely progressive disease, which may require development of innovative treatment strategies. This review discusses the first- and second-generation ALK inhibitors approved or in clinical development, as well as the novel challenges and approaches to disease progression in patients on targeted agents. Implications for Practice: The identification of driver mutations in non-small cell lung cancer (NSCLC), most prominently epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), has expanded treatment options for a significant cohort of patients. However, the success of targeted agents has brought new challenges, particularly regarding management of progression. Progression manifests heterogeneously, and management of oligoprogression may differ from diffusely progressive disease. Multiple options for treatment at progression exist, and it is becoming evident that selecting the best avenue of care requires understanding the biology and potential drivers of disease progression. This review discusses the array of treatment options available for patients with ALK-positive NSCLC, as well as evaluation and treatment of progressive disease. PMID:27053502

  17. Transdermal rivastigmine in the treatment of Alzheimer's disease: current and future directions.

    PubMed

    Amanatkar, Hamid Reza; Grossberg, George Thomas

    2014-10-01

    Despite the fact that the prevalence of Alzheimer's disease (AD) is exponentially increasing, we have not yet been able to develop a new treatment to modify the course of the disease. This vacuum makes the traditional cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonist the only accessible pharmacotherapy options for the treatment of this disease. Among these medications, the only available transdermal patch at this time is the rivastigmine patch. This patch provides significantly lower gastrointestinal adverse effects. A higher tolerability rate provides the option for physicians to continue treatment with higher doses of rivastigmine in advanced stages of AD. Moreover, ease of use, easy-to-follow schedule, less administration time spent by the caregiver result in greater adherent to the treatment. This article aims to provide a comprehensive drug profile for transdermal rivastigmine, to review currently available treatment options, and to try to anticipate future treatment directions for AD.

  18. Anti-angiogenesis target therapy for advanced osteosarcoma

    PubMed Central

    Xie, Lu; Ji, Tao; Guo, Wei

    2017-01-01

    Osteosarcomas (OS), especially those with metastatic or unresectable disease, have limited treatment options. The greatest advancement in treatments occurred in the 1980s when multi-agent chemotherapy, including doxorubicin, cisplatin, high-dose methotrexate, and, in some regimens, ifosfamide, was demonstrated to improve overall survival compared with surgery alone. However, standard chemotherapeutic options have been limited by poor response rates in patients with relapsed or advanced cases. It has been reported that VEGFR expression correlates with the outcome of patients with osteosarcoma and circulating VEGF level has been associated with the development of lung metastasis. At present, it seems to us that progress has not been made since Grignani reported a phase II cohort trial of sorafenib and sorafenib combined with everolimus for advanced osteosarcoma, which, in a sense, have become a milestone as a second-line therapy for osteosarcoma. Although the recognization of muramyltripepetide phosphatidyl-ethanolamine has made some progress based on its combination with standard chemotherapy, its effect on refractory cases is controversial. Personalized comprehensive molecular profiling of high-risk osteosarcoma up to now has not changed the therapeutic prospect of advanced osteosarcoma significantly. Thus, how far have we moved forward and what therapeutic strategy should we prefer for anti-angiogenesis therapy? This review provides an overview of the most updated anti-angiogenesis therapy in OS and discusses some clinical options in order to maintain or even improve progression-free survival. PMID:28656259

  19. Management of localized and locally advanced renal tumors. A contemporary review of current treatment options.

    PubMed

    Brookman-May, S; Langenhuijsen, J F; Volpe, A; Minervini, A; Joniau, S; Salagierski, M; Roscigno, M; Akdogan, B; Vandromme, A; Rodriguez-Faba, O; Marszalek, M

    2013-06-01

    About 70% of patients with renal cell carcinoma present with localized or locally advanced disease at primary diagnosis. Whereas these patients are potentially curable by surgical treatment alone, a further 20% to 30% of patients are diagnosed with primary metastatic disease. Although over the past years medical treatment for metastatic patients has nearly completely changed from immunotherapy to effective treatment with targeted agents, metastatic disease still represents a disease status which is not curable. Also in patients with metastatic disease, surgical treatment of the primary tumor plays an important role, since local tumor related complications can be avoided or minimized by surgery. Furthermore, also improvement of overall survival has been proven for surgery in metastatic patients when combined with cytokine treatment. Hence, surgical combined with systemic treatment as a multi-modal, adjuvant, and neo-adjuvant treatment is also required in patients with advanced or metastatic disease. A growing number of elderly and comorbid patients are currently diagnosed with small renal masses, which has led to increased attention paid to alternative ablative treatment modalities as well as active surveillance strategies, which are applied in order to avoid unnecessary overtreatment in these patients. Since surgical treatment also might enhance the risk of chronic kidney disease with consecutive cardiac disorders as well as reduced overall survival, ablative techniques and active surveillance are increasingly applied. In this review article we focus on current surgical and none-surgical treatment options for the management of patients with localized, locally advanced, and metastatic renal cell carcinoma.

  20. A multidisciplinary prostate cancer clinic for newly diagnosed patients: developing the role of the advanced practice nurse.

    PubMed

    Madsen, Lydia T; Craig, Catherine; Kuban, Deborah

    2009-06-01

    Newly diagnosed patients with prostate cancer have various treatment options, and a multidisciplinary prostate cancer clinic (MPCC) can present all options in a single setting. An MPCC was started in 2004 at the University of Texas M.D. Anderson Cancer Center, and 258 patients with prostate cancer were evaluated in its first year. The clinic expanded in 2006 and an oncology advanced practice nurse (APN) was recruited to address specific objectives. The APN role was used to implement a quality-of-life protocol, provide detailed patient education (including a treatment summary and care plan), and serve as a single point of contact as patients move toward a treatment decision. Formal evaluation of the MPCC showed that patients were satisfied with this approach to the complex decision-making process in prostate cancer.

  1. Potential role for mammalian target of rapamycin inhibitors as first-line therapy in hormone receptor–positive advanced breast cancer

    PubMed Central

    Beck, J Thaddeus

    2015-01-01

    Despite advances in cytotoxic chemotherapy and targeted therapies, 5-year survival rates remain low for patients with advanced breast cancer at diagnosis. This highlights the limited effectiveness of current treatment options. An improved understanding of cellular functions associated with the development and progression of breast cancer has resulted in the creation of a number of novel targeted molecular therapies. However, more work is needed to improve outcomes, particularly in the first-line recurrent or metastatic hormone receptor–positive breast cancer setting. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) pathway is a major intracellular signaling pathway that is often upregulated in breast cancer, and overactivation of this pathway has been associated with primary or developed resistance to endocrine treatment. Clinical data from the Phase III Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2) study of the mTOR inhibitor everolimus combined with exemestane in hormone receptor–positive advanced breast cancer were very promising, highlighting the potential role of mTOR inhibitors in combination with endocrine therapies as a first-line treatment option for these patients. It is hoped that the use of mTOR inhibitors combined with current standard-of-care endocrine therapies, such as aromatase inhibitors, in the first-line advanced breast cancer setting may result in greater antitumor effects and also delay or reverse treatment resistance. PMID:26675495

  2. Advanced Management of Severe Keloids.

    PubMed

    Hagele, Thomas; Nyanda, Hoka; Patel, Nishit; Russell, Nicole; Cohen, George; Nelson, Christopher

    2017-01-01

    Keloids negatively impact the health and quality of life of many affected dermatologic patients. Treating keloids is often difficult, and suboptimal responses are frequent. Fortunately, there are many treatment options available to the clinician that may lead to improved clinical outcomes. We present a review of currently available therapeutic options. Intralesional steroid injection remains the first-line treatment for keloids. Imiquimod, direct interferon therapy, or intralesional 5-flurouracil may alleviate the need for excessive corticosteroid therapy. Radiation and laser therapy are emerging therapeutic options that have demonstrated efficacy in reviewed studies. Given the unsatisfactory outcomes associated with pressure dressings, vitamin E, ablative laser, and surgical excision, these options should be avoided in keloid management. Further research is needed to evaluate the efficacy and recurrence associated with the reviewed therapeutics.

  3. [Anal fissure of cryptoglandular origin. Therapeutic options].

    PubMed

    Casal, Enrique; de San Ildefonso, Alberto; Sánchez, Juan; Facal, Cristina; Pampin, José

    2005-12-01

    Anal fistula is a frequent condition. The most commonly accepted origin is infectious. The most widely used classification is based on cryptoglandular theory and on the position of the fistulous tract in relation to the anal sphincter. Physical examination will help to identify the type of fistula and allow its treatment to be planned. The most widely used complementary tests are endoanal ultrasound and magnetic resonance imaging. We review the various therapeutic options and their results, especially fistulotomy, endorectal advancement flap, use of sedal, anodermal advancement flap, sphincterorrhaphy with sphincter repair, and fibrin glue.

  4. Osimertinib: A Review in T790M-Positive Advanced Non-Small Cell Lung Cancer.

    PubMed

    Lamb, Yvette N; Scott, Lesley J

    2017-08-01

    Osimertinib (Tagrisso™) is an oral, CNS-active, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets EGFR TKI-sensitizing mutations and, crucially, the T790M mutation that often underlies acquired resistance to EGFR TKI therapy. Osimertinib has been approved in numerous countries for use in patients with T790M-positive advanced NSCLC. In the pivotal, international AURA3 trial in patients with T790M-positive advanced NSCLC who had disease progression after EGFR TKI therapy, osimertinib treatment significantly prolonged progression-free survival (PFS; primary endpoint) compared with platinum-pemetrexed therapy at the time of the primary analysis. PFS results were consistent across predefined subgroups of patients, including those with CNS metastases at baseline. There was no difference between treatment groups in overall survival at 26% maturity. Objective response rates (ORRs) and patient-reported outcomes for prespecified symptoms were also significantly improved with osimertinib relative to platinum-pemetrexed, with CNS ORRs in patients with CNS metastases more than twofold higher in the osimertinib than in the platinum-pemetrexed group. Osimertinib had a manageable tolerability profile, with relatively few patients permanently discontinuing treatment because of adverse events (AEs). With limited treatment options available in this setting, osimertinib is an important option in adult patients with advanced EGFR T790M-positive NSCLC.

  5. Sowing seeds: transperineal implantation.

    PubMed

    Amerine, E; Nagle, G M; Bollinger, J R

    2000-02-01

    Prostate cancer, the second leading cause of male deaths in the United States, has increased by 126% since 1987 (Stephenson, 1998). Early diagnosis is attributed to public awareness and technologic advances. Multiple options for definitive treatment with equally positive outcomes dramatically influence the patient's decision-making process. One popular option for these patients is transperineal implantation of radioactive seeds into the prostate.

  6. Challenges in shared decision making in advanced cancer care: a qualitative longitudinal observational and interview study.

    PubMed

    Brom, Linda; De Snoo-Trimp, Janine C; Onwuteaka-Philipsen, Bregje D; Widdershoven, Guy A M; Stiggelbout, Anne M; Pasman, H Roeline W

    2017-02-01

    Patients' preferences and expectations should be taken into account in treatment decision making in the last phase of life. Shared decision making (SDM) is regarded as a way to give the patient a central role in decision making. Little is known about how SDM is used in clinical practice in advanced cancer care. To examine whether and how the steps of SDM can be recognized in decision making about second- and third-line chemotherapy. Fourteen advanced cancer patients were followed over time using face-to-face in-depth interviews and observations of the patients' out-clinic visits. Interviews and outpatient clinic visits in which treatment options were discussed or decisions made were transcribed verbatim and analysed using open coding. Patients were satisfied with the decision-making process, but the steps of SDM were barely seen in daily practice. The creation of awareness about available treatment options by physicians was limited and not discussed in an equal way. Patients' wishes and concerns were not explicitly assessed, which led to different expectations about improved survival from subsequent lines of chemotherapy. To reach SDM in daily practice, physicians should create awareness of all treatment options, including forgoing treatment, and communicate the risk of benefit and harm. Open and honest communication is needed in which patients' expectations and concerns are discussed. Through this, the difficult process of decision making in the last phase of life can be facilitated and the focus on the best care for the specific patient is strengthened. © 2015 The Authors. Health Expectations Published by John Wiley & Sons Ltd.

  7. Therapeutic options for intractable hematuria in advanced bladder cancer.

    PubMed

    Abt, Dominik; Bywater, Mirjam; Engeler, Daniel Stephan; Schmid, Hans-Peter

    2013-07-01

    Intractable hematuria is a common and severe complication in patients with inoperable bladder carcinoma. The aim was to provide an overview of therapeutic options for such cases, and analyze their effectiveness and risk profile, so a systematic literature search of peer-reviewed papers published up to September 2012 was carried out. Various options are available to treat hematuria in patients with inoperable bladder cancer; these include orally administered epsilon-aminocaproic acid, intravesical formalin, alum or prostaglandin irrigation, hydrostatic pressure, urinary diversion, radiotherapy, embolization and intraarterial mitoxantrone perfusion. These treatment options are associated with different prospects of success, risks and side-effects. Well-designed and large studies comparing options are completely lacking. Despite various treatment options, management of intractable hematuria in patients with inoperable bladder cancer remains a challenge, and most of the reported methods should be seen as experimental. Interventional radiology and alum instillation seem to be suitable alternative options for patients who, after critical consideration, cannot be treated by irrigation, transurethral resection or palliative cystectomy. © 2013 The Japanese Urological Association.

  8. Management options of varicoceles

    PubMed Central

    Chan, Peter

    2011-01-01

    Varicocele is one of the most common causes of male infertility. Treatment options for varicoceles includes open varicocelectomy performed at various anatomical levels. Laparoscopic varicocelectomy has been established to be a safe and effective treatment for varicoceles. Robotic surgery has been introduced recently as an alternative surgical option for varicocelectomy. Microsurgical varicocelectomy has gained increasing popularity among experts in male reproductive medicine as the treatment of choice for varicocele because of its superior surgical outcomes. There is a growing volume of literature in the recent years on minimal invasive varicocele treatment with percutaneous retrograde and anterograde venous embolization/sclerotherapy. In this review, we will discuss the advantages and limitations associated with each treatment modality for varicoceles. Employment of these advanced techniques of varicocelectomy can provide a safe and effective approach aiming to eliminate varicocele, preserve testicular function and, in a substantial number of men, increase semen quality and the likelihood of pregnancy. PMID:21716892

  9. Medial tibial stress syndrome: conservative treatment options.

    PubMed

    Galbraith, R Michael; Lavallee, Mark E

    2009-10-07

    Medial tibial stress syndrome (MTSS), commonly known as "shin splints," is a frequent injury of the lower extremity and one of the most common causes of exertional leg pain in athletes (Willems T, Med Sci Sports Exerc 39(2):330-339, 2007; Korkola M, Amendola A, Phys Sportsmed 29(6):35-50, 2001; Hreljac A, Med Sci Sports Exerc 36(5):845-849, 2004). Although often not serious, it can be quite disabling and progress to more serious complications if not treated properly. Often, the cause of MTSS is multi-factorial and involves training errors and various biomechanical abnormalities. Few advances have been made in the treatment of MTSS over the last few decades. Current treatment options are mostly based on expert opinion and clinical experience. The purpose of this article is to review published literature regarding conservative treatment options for MTSS and provide recommendations for sports medicine clinicians for improved treatment and patient outcomes.

  10. Membrane Distillation Bioreactor (MDBR) - A lower Green-House-Gas (GHG) option for industrial wastewater reclamation.

    PubMed

    Goh, Shuwen; Zhang, Jinsong; Liu, Yu; Fane, Anthony G

    2015-12-01

    A high-retention membrane bioreactor system, the Membrane Distillation Bioreactor (MDBR) is a wastewater reclamation process which has the potential to tap on waste heat generated in industries to produce high quality product water. There are a few key factors which could make MDBR an attractive advanced treatment option, namely tightening legal requirements due to increasing concerns on the micropollutants in industrial wastewater effluents as well as concerns over the electrical requirement of pressurized advanced treatment processes and greenhouse gas emissions associated with wastewater reclamation. This paper aims to provide a consolidated review on the current state of research for the MDBR system and to evaluate the system as a possible lower Green House Gas (GHG) emission option for wastewater reclamation using the membrane bioreactor-reverse osmosis (MBR-RO) system as a baseline for comparison. The areas for potential applications and possible configurations for MDBR applications are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Apatinib in the treatment of advanced lung adenocarcinoma with KRAS mutation.

    PubMed

    Zeng, Da-Xiong; Wang, Chang-Guo; Huang, Jian-An; Jiang, Jun-Hong

    2017-01-01

    Activating KRAS mutations in lung adenocarcinoma are characterized with treatment resistance and poor prognosis. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase, apatinib has been proven successful in advanced gastric cancer and breast cancer. In this study, we show the result of apatinib as salvage treatment in lung adenocarcinoma patients with KRAS mutation. Four advanced lung adenocarcinoma patients with KRAS mutation were orally administered apatinib (250 mg/d) after second-line treatment. One patient showed progressive disease, while 3 patients showed stable disease response to apatinib, with a median progression-free survival (PFS) of 3.8 months (1.5-5.5 months). The main toxicities were hoarseness and hemoptysis, which were manageable. Therefore, apatinib might be an optional choice for advanced lung adenocarcinoma patients with KRAS mutation in post second-line treatment.

  12. Erectile Dysfunction: A Review of Historical Treatments With a Focus on the Development of the Inflatable Penile Prosthesis

    PubMed Central

    Gurtner, Kristen; Saltzman, Amanda; Hebert, Kristi; Laborde, Eric

    2015-01-01

    Erectile dysfunction has been a concern for men since the beginning of written history. For many men it can lead to severe psychological distress and humiliation. The treatment of erectile dysfunction has advanced significantly over the past 200 years. Men today are presented with many more viable therapy options leading to improved efficacy and more satisfactory sex lives. The objective of this article is to explore historical options for the treatment of erectile dysfunction, with particular emphasis on the development and progression of the inflatable penile prosthesis. PMID:26206161

  13. Advances in Proximal Interphalangeal Joint Arthroplasty: Biomechanics and Biomaterials.

    PubMed

    Zhu, Andy F; Rahgozar, Paymon; Chung, Kevin C

    2018-05-01

    Proximal interphalangeal (PIP) joint arthritis is a debilitating condition. The complexity of the joint makes management particularly challenging. Treatment of PIP arthritis requires an understanding of the biomechanics of the joint. PIP joint arthroplasty is one treatment option that has evolved over time. Advances in biomaterials have improved and expanded arthroplasty design. This article reviews biomechanics and arthroplasty design of the PIP joint. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Recent Advances in Monoclonal Antibody Therapies for Multiple Sclerosis.

    PubMed

    Wootla, Bharath; Watzlawik, Jens O; Stavropoulos, Nikolaos; Wittenberg, Nathan J; Dasari, Harika; Abdelrahim, Murtada A; Henley, John R; Oh, Sang-Hyun; Warrington, Arthur E; Rodriguez, Moses

    2016-06-01

    Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating disease of the CNS and results in neurological disability. Existing immunomodulatory and immunosuppressive approaches lower the number of relapses but do not cure or reverse existing deficits nor improve long-term disability in MS patients. Monogenic antibodies were described as treatment options for MS, however the immunogenicity of mouse antibodies hampered the efficacy of potential therapeutics in humans. Availability of improved antibody production technologies resulted in a paradigm shift in MS treatment strategies. In this review, an overview of immunotherapies for MS that use conventional monoclonal antibodies reactive to immune system and their properties and mechanisms of action will be discussed, including recent advances in MS therapeutics and highlight natural autoantibodies (NAbs) that directly target CNS cells. Recent challenges for MS therapy are the identification of relevant molecular and cellular targets, time frame of treatment, and antibody toxicity profiles to identify safe treatment options for MS patients. The application of monoclonal antibody therapies with better biological efficacy associated with minimum side effects possesses huge clinical potential. Advances in monoclonal antibody technologies that directly target cells of nervous system may promote the CNS regeneration field from bench to bedside.

  15. Recent Advances in Monoclonal Antibody Therapies for Multiple Sclerosis

    PubMed Central

    Stavropoulos, Nikolaos; Wittenberg, Nathan J.; Dasari, Harika; Abdelrahim, Murtada A.; Henley, John R.; Oh, Sang-Hyun; Warrington, Arthur E.; Rodriguez, Moses

    2016-01-01

    Introduction Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating disease of the CNS and results in neurological disability. Existing immunomodulatory and immunosuppressive approaches lower the number of relapses but do not cure or reverse existing deficits nor improve long-term disability in MS patients. Areas Covered Monogenic antibodies were described as treatment options for MS, however the immunogenicity of mouse antibodies hampered the efficacy of potential therapeutics in humans. Availability of improved antibody production technologies resulted in a paradigm shift in MS treatment strategies. In this review, an overview of immunotherapies for MS that use conventional monoclonal antibodies reactive to immune system and their properties and mechanisms of action will be discussed, including recent advances in MS therapeutics and highlight natural autoantibodies (NAbs) that directly target CNS cells. Expert Opinion Recent challenges for MS therapy are the identification of relevant molecular and cellular targets, time frame of treatment, and antibody toxicity profiles to identify safe treatment options for MS patients. The application of monoclonal antibody therapies with better biological efficacy associated with minimum side effects possesses huge clinical potential. Advances in monoclonal antibody technologies that directly target cells of nervous system may promote the CNS regeneration field from bench to bedside. PMID:26914737

  16. Revving up the immune therapy business.

    PubMed

    2015-08-01

    Giant pharmaceutical companies and biotech startups are seizing opportunities to advance their oncologic immunotherapy business and provide patients with more-effective treatment options. ©2015 American Association for Cancer Research.

  17. Locally advanced and metastatic basal cell carcinoma: molecular pathways, treatment options and new targeted therapies.

    PubMed

    Ruiz Salas, Veronica; Alegre, Marta; Garcés, Joan Ramón; Puig, Lluis

    2014-06-01

    The hedgehog (Hh) signaling pathway has been identified as important to normal embryonic development in living organisms and it is implicated in processes including cell proliferation, differentiation and tissue patterning. Aberrant Hh pathway has been involved in the pathogenesis and chemotherapy resistance of different solid and hematologic malignancies. Basal cell carcinoma (BCC) and medulloblastoma are two well-recognized cancers with mutations in components of the Hh pathway. Vismodegib has recently approved as the first inhibitor of one of the components of the Hh pathway (smoothened). This review attempts to provide current data on the molecular pathways involved in the development of BCC and the therapeutic options available for the treatment of locally advanced and metastatic BCC, and the new targeted therapies in development.

  18. Individualized Health Care Plans: Supporting Children With Chronic Conditions in the Classroom

    ERIC Educational Resources Information Center

    Hopkins, Amanda F.; Hughes, Mary-alayne

    2016-01-01

    Due to the major advances in technology and the sciences, advances in the medical treatment options for children with chronic conditions are being made at an astonishing rate. In the health care field, "children with chronic conditions" is a generic phrase that typically refers to children with physical, developmental, behavioral, or…

  19. Advance care planning and proxy decision making for patients with advanced Parkinson disease.

    PubMed

    Kwak, Jung; Wallendal, Maggie S; Fritsch, Thomas; Leo, Gary; Hyde, Trevor

    2014-03-01

    To examine advance care planning practices and proxy decision making by family healthcare proxies for patients with advanced Parkinson disease (PD). Sixty-four spouses and adult children, self-designated as a/the healthcare proxy for advanced patients with PD, participated in a cross-sectional survey study. Sixty patients with PD (95%) had completed a living will, but only 38% had shared the document with a physician. Among three life-support treatments--cardiopulmonary resuscitation (CPR), ventilator, and feeding tube--47% of patients opted for CPR, 16% for ventilator, and 20% for feeding tube. Forty-two percent of proxies did not know patients' preferences for one or more of the three life-support treatments. Only 28% of proxies reported that patients wanted hospice. Patients who shared advance directives with a physician were significantly less likely to choose CPR and a feeding tube and they were more likely to choose hospice. In a hypothetical end-of-life (EOL) scenario, the majority of proxies chose comfort care as the EOL goal of care (53%) and pain and symptom management only as the course of treatment option (72%); these proxy choices for patients, however, were not associated with patients' preferences for life support. Patients' proxies preferred a form of shared decision making with other family members and physicians. Advance care planning is effective when patients, families, and healthcare professionals together consider future needs for EOL care decisions. Further efforts are needed by healthcare professionals to provide evidence-based education about care options and facilitate advanced discussion and shared decision making by the patient and families.

  20. Recent advances in understanding and treating vasculitis

    PubMed Central

    Koster, Matthew J.; Warrington, Kenneth J.

    2016-01-01

    Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are near universally fatal conditions if untreated. Although effective therapeutic options are available for these diseases, treatment regimens are associated with both short- and long-term adverse effects. The recent identification of effective B-cell-targeted therapy with an anti-CD20 monoclonal antibody has transformed the treatment landscape of AAV. Questions, nevertheless, remain regarding the appropriate timing, dose, frequency, duration, and long-term effects of treatment. The aim of this article is to provide an overview of the current information, recent advances, ongoing clinical trials, and future treatment possibilities in AAV. PMID:27347395

  1. Review of hormone-based treatments in postmenopausal patients with advanced breast cancer focusing on aromatase inhibitors and fulvestrant

    PubMed Central

    Kümler, Iben; Knoop, Ann S; Jessing, Christina A R; Ejlertsen, Bent; Nielsen, Dorte L

    2016-01-01

    Background Endocrine therapy constitutes a central modality in the treatment of oestrogen receptor (ER)-positive advanced breast cancer. Purpose To evaluate the evidence for endocrine treatment in postmenopausal patients with advanced breast cancer focusing on the aromatase inhibitors, letrozole, anastrozole, exemestane and fulvestrant. Methods A review was carried out using PubMed. Randomised phase II and III trials reporting on ≥100 patients were included. Results 35 trials met the inclusion criteria. If not used in the adjuvant setting, a non-steroid aromatase inhibitor was the optimal first-line option. In general, the efficacy of the different aromatase inhibitors and fulvestrant was similar in tamoxifen-refractory patients. A randomised phase II trial of palbociclib plus letrozole versus letrozole alone showed significantly increased progression-free survival (PFS) when compared with endocrine therapy alone in the first-line setting (20.2 vs 10.2 months). Furthermore, the addition of everolimus to exemestane in the Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) study resulted in an extension of median PFS by 4.5 months after recurrence/progression on a non-steroid aromatase inhibitor. However, overall survival was not significantly increased. Conclusion Conventional treatment with an aromatase inhibitor or fulvestrant may be an adequate treatment option for most patients with hormone receptor-positive advanced breast cancer. Mammalian target of rapamycin (mTOR) inhibition and cyclin-dependent kinase 4/6 (CDK4/6) inhibition might represent substantial advances for selected patients in some specific settings. However, there is an urgent need for prospective biomarker-driven trials to identify patients for whom these treatments are cost-effective. PMID:27843622

  2. Cetuximab with radiotherapy as an alternative treatment for advanced squamous cell carcinoma of the temporal bone.

    PubMed

    Ebisumoto, Koji; Okami, Kenji; Hamada, Masashi; Maki, Daisuke; Sakai, Akihiro; Saito, Kosuke; Shimizu, Fukuko; Kaneda, Shoji; Iida, Masahiro

    2018-06-01

    The prognosis of advanced temporal bone cancer is poor, because complete surgical resection is difficult to achieve. Chemoradiotherapy is one of the available curative treatment options; however, its systemic effects on the patient restrict the use of this treatment. A 69-year-old female (who needed peritoneal dialysis) presented at our clinic with T4 left external auditory canal cancer and was treated with cetuximab plus radiotherapy (RT). The primary lesion showed complete response. The patient is currently alive with no evidence of disease two years after completion of the treatment and does not show any late toxicity. This is the first advanced temporal bone cancer patient treated with RT plus cetuximab. Cetuximab plus RT might be a treatment alternative for patients with advanced temporal bone cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Upper extremity limb loss: functional restoration from prosthesis and targeted reinnervation to transplantation.

    PubMed

    Carlsen, Brian T; Prigge, Pat; Peterson, Jennifer

    2014-01-01

    For several decades, prosthetic use was the only option to restore function after upper extremity amputation. Recent years have seen advances in the field of prosthetics. Such advances include prosthetic design and function, activity-specific devices, improved aesthetics, and adjunctive surgical procedures to improve both form and function. Targeted reinnervation is one exciting advance that allows for more facile and more intuitive function with prosthetics following proximal amputation. Another remarkable advance that holds great promise in nearly all fields of medicine is the transplantation of composite tissue, such as hand and face transplantation. Hand transplantation holds promise as the ultimate restorative procedure that can provide form, function, and sensation. However, this procedure still comes with a substantial cost in terms of the rehabilitation and toxic immunosuppression and should be limited to carefully selected patients who have failed prosthetic reconstruction. Hand transplantation and prosthetic reconstruction should not be viewed as competing options. Rather, they are two treatment options with different risk/benefit profiles and different indications and, hence vastly different implications. Copyright © 2014 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

  4. LATEST LASER AND LIGHT-BASED ADVANCES FOR ETHNIC SKIN REJUVENATION

    PubMed Central

    Elsaie, Mohamed Lotfy; Lloyd, Heather Woolery

    2008-01-01

    Background: Advances in nonablative skin rejuvenation technologies have sparked a renewed interest in the cosmetic treatment of aging skin. More options exist now than ever before to reverse cutaneous changes caused by long-term exposure to sunlight. Although Caucasian skin is more prone to ultraviolet light injury, ethnic skin (typically classified as types IV to VI) also exhibits characteristic photoaging changes. Widespread belief that inevitable or irreversible textural changes or dyspigmentation occurs following laser- or light-based treatments, has been challenged in recent years by new classes of devices capable of protecting the epidermis from injury during treatment. Objective: The purpose of this article is to review recent clinical advances in the treatment of photoaging changes in ethnic skin. This article provides a basis for the classification of current advances in nonablative management of ethnic skin. PMID:19881986

  5. Treatment options after sorafenib failure in patients with hepatocellular carcinoma

    PubMed Central

    Dika, Imane El

    2017-01-01

    Second line therapy after failure of sorafenib continues to be under study. Prognosis of hepatocellular carcinoma is measured in months, with median overall survival reaching 10.7 months with sorafenib. Because of the modest net benefit sorafenib has contributed, and rising incidence of hepatocellular carcinoma in the world, continued efforts are ongoing to look for efficient upfront, second line, or combination therapies. Herein we review the most relevant to date published literature on treatment options beyond sorafenib, reported studies, ongoing investigational efforts, and possibilities for future studies in advanced hepatocellular carcinoma. PMID:29151326

  6. Immunotherapy for lung cancer: advances and prospects.

    PubMed

    Yang, Li; Wang, Liping; Zhang, Yi

    2016-01-01

    Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths worldwide. To date, surgery is the first choice treatment, but most clinically diagnosed cases are inoperable. While chemotherapy and/or radiotherapy are the next considered options for such cases, these treatment modalities have adverse effects and are sometimes lethal to patients. Thus, new effective strategies with minimal side effects are urgently needed. Cancer immunotherapy provides either active or passive immunity to target tumors. Multiple immunotherapy agents have been proposed and tested for potential therapeutic benefit against lung cancer, and some pose fewer side effects as compared to conventional chemotherapy and radiotherapy. In this article, we discuss studies focusing on interactions between lung cancer and the immune system, and we place an emphasis on outcome evidence in order to create a knowledge base well-grounded in clinical reality. Overall, this review highlights the need for new lung cancer treatment options, with much ground to be paved for future advances in the field. We believe that immunotherapy agents alone or with other forms of treatment can be recognized as next modality of lung cancer treatment.

  7. [New physiopathological knowledge applied to migraine therapy and prophylaxis].

    PubMed

    Visens, Laura S

    2014-01-01

    Migraine is a very common condition that has a significant socioeconomic impact. Based on the most recent reports from the World Health Organization, its diagnosis and treatment are far from being optimal. Specialists have made great efforts to classify headaches, including migraines, in order to have a useful diagnostic tool and to guide treatment. On the other hand, advances made in the knowledge of the pathophysiology of migraines, new treatment options were developed. These new options include onabotulinum toxin A and topiramate. The prompt detection of migraine disorders and an appropriate treatment, both symptomatic and preventive, are key to relieve the personal, familiar, and social burden with special focus on chronic migraine.

  8. Penile Reconstruction

    PubMed Central

    Salgado, Christopher J.; Chim, Harvey; Tang, Jennifer C.; Monstrey, Stan J.; Mardini, Samir

    2011-01-01

    A variety of surgical options exists for penile reconstruction. The key to success of therapy is holistic management of the patient, with attention to the psychological aspects of treatment. In this article, we review reconstructive modalities for various types of penile defects inclusive of partial and total defects as well as the buried penis, and also describe recent basic science advances, which may promise new options for penile reconstruction. PMID:22851914

  9. Electrochemotherapy efficacy evaluation for treatment of locally advanced stage III cutaneous squamous cell carcinoma: a 22-cases retrospective analysis.

    PubMed

    Di Monta, Gianluca; Caracò, Corrado; Simeone, Ester; Grimaldi, Antonio Maria; Marone, Ugo; Di Marzo, Massimiliano; Vanella, Vito; Festino, Lucia; Palla, Marco; Mori, Stefano; Mozzillo, Nicola; Ascierto, Paolo Antonio

    2017-04-26

    Extensive squamous cell carcinoma has few therapeutic options. In such cases, electrochemotherapy involving electroporation combined with antineoplastic drug appears to be a new potential option and may be considered as an alternative treatment. The aim of this retrospective single-center study was to evaluate electrochemotherapy efficacy in treatment of locally advanced stage III squamous cell carcinoma, in which surgical procedures would have entailed wide tissue sacrifice. Clinical features, treatment response, and adverse effects were evaluated in 22 patients treated with electrochemotherapy with intravenous injection of bleomycin for extensive stage III cutaneous squamous cell carcinoma. Treatment of cutaneous lesions were performed according to the European Standard Operating Procedures of Electrochemotherapy. Overall response to electrochemotherapy treatment was observed in 18 (81.8%) patients. Clinical response with necrosis of tumor mass was observed from the first session and lasted for all follow up period that ranged between 5 and 48 months with a median of 34 months. Overall the treatment was well tolerated with a very low complication rate. Electrochemotherapy represents a safe and effective therapeutic approach, associated with a good tolerability.

  10. ADVANCED OXIDATION PROCESSES (AOPS) FOR DESTRUCTION OF METHYL TERTIARY BUTYL ETHER (MTBE -AN UNREGULATED CONTAMINANT) IN DRINKING WATER

    EPA Science Inventory

    Advanced oxidation processes (AOPs) provide a promising treatment option for the destruction of MTBE directly in surface and ground waters. An ongoing study is evaluating the ability of three AOPs; hydrogen peroxide/ozone (H2O2/ O3), ultraviolet irradiation/ozone (UV/O3) and ultr...

  11. Efficiency of low dosage apatinib in post-first-line treatment of advanced lung adenocarcinoma.

    PubMed

    Zeng, Da-Xiong; Wang, Chang-Guo; Lei, Wei; Huang, Jian-An; Jiang, Jun-Hong

    2017-09-12

    Chemotherapy is the standard treatment of in advanced lung adenocarcinoma patients without driver mutation. However, few drugs could be selected when diseases progressed after second-line treatment. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), apatinib was suggested mainly using in advanced gastric cancer. In this study, we showed the results of apatinib as second-line to fourth-line treatment in EGFR wild-type advanced lung adenocarcinoma patients. 16 EGFR wild-type advanced lung adenocarcinoma patients were administrated apatinib (250-500 mg/d) orally. 3 patients showed partial response and 8 patients showed stable diseases response to apatinib, with a medium progression-free survival (PFS) of 4.4 month (2-10 months). The objective remission rate (ORR) was 18.75%(3/16). The total disease control rate (DCR) was 68.75% (11/16). The main toxicities were hypertension, hand-foot syndrome, proteinuria and thrombocytopenia which were tolerable and manageable. So, apatinib might be an optional choice for post-first-line treatment of EGFR wild-type advanced lung adenocarcinoma patients.

  12. [Therapeutic options for pressure ulcers].

    PubMed

    Damert, H-G; Meyer, F; Altmann, S

    2015-04-01

    The aim of this overview is based on remarks on the pathogenesis of and therapy for pressure ulcers and selected but representative cases to demonstrate current options of plastic coverage. As a consequence of the demographic developments, in particular, with regard to the increasing proportion of older patients as well as the advances in modern medicine, the number of multimorbid, geriatric and bedridden patients and of those with prolonged sickbed periods has been steadily growing. Therefore, partly severe manifestations of pressure ulcers at various exposed body regions can be observed in spite of the best preventive intention of care. While in the early stages rather conservative treatment is adequate, surgical intervention might become important and indispensable for a sufficient treatment in advanced stages. To facilitate basic care and to appropriately treat the infectious focus, the methods and procedures of plastic surgery can become relevant. Although there are several options and approaches existing to sanitise and cover defects of pressure ulcers, which are described within the article based on representative cases, preventive measures can still be considered the best approach. Georg Thieme Verlag KG Stuttgart · New York.

  13. An Update on Triptorelin: Current Thinking on Androgen Deprivation Therapy for Prostate Cancer.

    PubMed

    Merseburger, Axel S; Hupe, Marie C

    2016-07-01

    Androgen deprivation therapy (ADT) is the mainstay palliative treatment for men with locally advanced and metastatic prostate cancer, and aims to reduce testosterone to levels obtained by surgical castration. Use of gonadotropin-releasing hormone (GnRH) agonists predominates among the ADT options. The GnRH agonist, triptorelin is a first-line hormonal therapy that has demonstrated efficacy and safety in clinical trials of patients with locally advanced non-metastatic or metastatic disease. Sustained-release 1-, 3- and 6-month formulations of triptorelin, administered intramuscularly or subcutaneously, have been developed to provide improved flexibility and convenience for the patient. Head-to-head studies of GnRH agonists are lacking in the field of prostate cancer. Despite the inevitable progression to castration-resistant prostate cancer (CRPC) in most patients receiving ADT, monitoring of testosterone levels needs to improve in routine practice and physicians should not overlook the benefits of continued ADT in their patients when introducing one of the various new treatment options for CRPC. For improved survival outcomes, there remains a need to tailor ADT treatment regimens, novel hormonal agents and chemotherapy according to the individual patient with advanced prostate cancer.

  14. Non-extraction treatment of a Class III skeletal case.

    PubMed

    Gonzalez, Bulmario

    2009-01-01

    Adult Class III Skeletal treatment options have generally included some form of surgery (Maxillary advancement in midface deficient cases and/or Mandibular set-back). This article discusses non-surgical treatment of an adult patient using the combined concepts of mandibular molar distalization enhanced with TADs and non-extraction camouflage dental correction through maxillary incisor protraction and mandibular incisor lingualization.

  15. Effectiveness of Maxillomandibular advancement (MMA) surgery in sleep apnea treatment: Case report.

    PubMed

    Ferraz, Otávio; Guimarães, Thais M; Rossi, Rowdley R; Cunali, Paulo A; Fabbro, Cibele Dal; Chaves, Cauby M; Maluly, Milton; Bittencourt, Lia; Tufik, Sergio

    2016-01-01

    Obstructive sleep apnea (OSA) is characterized by episodes of pharyngeal collapse during sleep. Craniofacial alterations such as retrognathia are often found in OSA patients. Maxillomandibular advancement (MMA) surgeries increase the pharyngeal space and are a treatment option for OSA. The aim of this study was to present a successful case of MMA surgery in the treatment of OSA. A patient with moderate OSA (apnea-hypopnea index (AHI)=25.2) and mandibular retrognathism and Maxillomandibular asymmetry underwent MMA surgery. The apnea-hypopnea index (AHI) were considerably improved after six months (IAH =6.7) and one year of treatment (IAH=0.2).

  16. Turning nuclear waste into glass

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pegg, Ian L.

    2015-02-15

    Vitrification has emerged as the treatment option of choice for the most dangerous radioactive waste. But dealing with the nuclear waste legacy of the Cold War will require state-of-the-art facilities and advanced glass formulations.

  17. Immunotherapy Expands Lung Cancer Treatment Options

    Cancer.gov

    Results from a large clinical trial show combining the immune checkpoint inhibitor pembrolizumab (Keytruda) with chemotherapy helped some patients with advanced cancer live longer. As this Cancer Currents post explains, the results will immediately affect patient care.

  18. [Current standards in the treatment of gastric cancer].

    PubMed

    Hacker, Ulrich; Lordick, Florian

    2015-08-01

    Endoscopic resection is established in the treatment of early gastric cancer. More advanced gastric cancer requires gastrectomy and D2 lymphadenectomy. Perioperative chemotherapy improves overall survival in locally advanced gastric cancer representing a standard of care. Locally advanced adenocarcinomas of the esophago-gastric junction can alternatively be treated with concurrent radiochemotherapy. In metastatic disease, systemic chemotherapy improves survival, quality of life and symptom control. Trastuzumab plus chemotherapy should be used together with first-line chemotherapy in HER2 positive gastric cancer patients. Second- and third-line therapy is now well established. The anti-VEGFR2 antibody Ramucirumab improves survival in second line treatment both as a monotherapy and in combination with paclitaxel and represents a novel treatment option. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Narrowing of the Coronary Sinus: A Device-Based Therapy for Persistent Angina Pectoris.

    PubMed

    Konigstein, Maayan; Verheye, Stefan; Jolicœur, E Marc; Banai, Shmuel

    2016-01-01

    Alongside the remarkable advances in medical and invasive therapies for the treatment of ischemic heart disease, an increasing number of patients with advanced coronary artery disease unsuitable for revascularization continue to suffer from angina pectoris despite optimal medical therapy. Patients with chronic angina have poor quality of life and increased levels of anxiety and depression. A considerable number of innovative therapeutic modalities for the treatment of chronic angina have been investigated over the years; however, none of these therapeutic options has become a standard of care, and none are widely utilized. Current treatment options for refractory angina focus on medical therapy and secondary risk factor modification. Interventions to create increased pressure in the coronary sinus may alleviate myocardial ischemia by forcing redistribution of coronary blood flow from the less ischemic subepicardium to the more ischemic subendocardium, thus relieving symptoms of ischemia. Percutaneous, transvenous implantation of a balloon expandable, hourglass-shaped, stainless steel mesh in the coronary sinus to create a fixed focal narrowing and to increase backwards pressure, may serve as a new device-based therapy destined for the treatment of refractory angina pectoris.

  20. Phase II trial suggests new drug can shrink tumors in advanced ovarian cancer | Center for Cancer Research

    Cancer.gov

    In an ongoing phase II trial led by Jung-Min Lee, M.D., an Investigator in CCR’s Women’s Malignancies Branch, using the drug prexasertib led to decreases in tumor size in patients with advanced ovarian cancer, known as high-grade serious ovarian carcinoma, who currently have limited treatment options. Read more…

  1. Recent advances in multidisciplinary management of hepatocellular carcinoma

    PubMed Central

    Gomaa, Asmaa I; Waked, Imam

    2015-01-01

    The incidence of hepatocellular carcinoma (HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplantation, and percutaneous ablation, whereas palliative treatments include trans-arterial chemoembolization (TACE), radioembolization, and systemic treatments. Due to the diversity of available treatment options and patients’ presentations, a multidisciplinary team should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved molecular-targeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC. PMID:25866604

  2. The continuing role of chemotherapy for advanced non-small cell lung cancer in the targeted therapy era.

    PubMed

    Lwin, Zarnie; Riess, Jonathan W; Gandara, David

    2013-10-01

    There have been remarkable advances in the targeted treatment of advanced non-small cell lung cancer (NSCLC) over the past several years. Survival outcomes are steadily improving as management paradigms shift in the diagnosis and treatment of advanced NSCLC. Customizing treatment based on histology and molecular typing has become a standard of care in this era of targeted therapy. While new chemotherapeutic agents have proven effective, the pivotal role of platinum-based chemotherapy doublets has been confirmed. Maintenance chemotherapy has become an option, but who to employ it in remains unclear in the real-world setting. Efforts to overcome resistance to targeted agents are ongoing utilizing combination regimens of chemotherapy plus targeted agents, but optimizing combination strategies needs further exploration. This review highlights recent developments in novel chemotherapeutics and in chemotherapy strategies over the past two years. Despite advances in molecular medicine, there remains an essential role for chemotherapy in advanced NSCLC, even in the recent targeted therapy era.

  3. Patients' views on the use of an Option Grid for knee osteoarthritis in physiotherapy clinical encounters: An interview study.

    PubMed

    Kinsey, Katharine; Firth, Jill; Elwyn, Glyn; Edwards, Adrian; Brain, Katherine; Marrin, Katy; Nye, Alan; Wood, Fiona

    2017-12-01

    Patient decision support tools have been developed as a means of providing accurate and accessible information in order for patients to make informed decisions about their care. Option Grids ™ are a type of decision support tool specifically designed to be used during clinical encounters. To explore patients' views of the Option Grid encounter tool used in clinical consultations with physiotherapists, in comparison with usual care, within a patient population who are likely to be disadvantaged by age and low health literacy. Semi-structured interviews with 72 patients (36 who had been given an Option Grid in their consultation and 36 who had not). Thematic analysis explored patients' understanding of treatment options, perceptions of involvement, and readability and utility of the Option Grid. Interviews suggested that the Option Grid facilitated more detailed discussion about the risks and benefits of a wider range of treatment options for osteoarthritis of the knee. Participants indicated that the Option Grid was clear and aided their understanding of a structured progression of the options as their condition advanced, although it was not clear whether the Option Grid facilitated greater engagement in shared decision making. The Option Grid for osteoarthritis of the knee was well received by patient participants who reported that it helped them to understand their options, and made the notion of choice explicit. Use of Option Grids should be considered within routine consultations. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

  4. Apatinib in gastric carcinoma: A case report of partial response for first-line treatment in advanced disease.

    PubMed

    Wang, Yaping; Bi, Minghong; Zhang, Haoran; Gao, Zhenyuan; Zhou, Hairong; Chang, Shu

    2017-10-01

    Gastric cancer (GC) is the most common gastrointestinal malignant tumor, with a gradual increasing incidence throughout the world. Mostly GC is diagnosed in its late stage. To date, there is no usable standardized treatment regimen for patients with advanced GC. Apatinib mesylate, small-molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor (TKI), has been approved as third-line treatment for patients with advanced gastric adenocarcinoma in China, October, 2014. Till now, there is no case report about apatinib as first-line treatment for patients with advanced GC in literature. We present an 83-year-old Chinese man with advanced gastric adenocarcinoma, who received apatinib as first-line option and obtained clinical benefit within 2 weeks. The lung metastases disappeared completely and the liver metastases shrank significantly. The patient's progression-free survival was 163 days and overall survival was 201 days. This paper reviews and discusses apatinib as a new targeted drug for patients with advanced GC by comparison with other effective molecular-targeted therapy. © 2016 John Wiley & Sons Australia, Ltd.

  5. Determining a sustainable and economically optimal wastewater treatment and discharge strategy.

    PubMed

    Hardisty, Paul E; Sivapalan, Mayuran; Humphries, Robert

    2013-01-15

    Options for treatment and discharge of wastewater in regional Western Australia (WA) are examined from the perspective of overall sustainability and social net benefit. Current practice in the state has typically involved a basic standard of treatment deemed to be protective of human health, followed by discharge to surface water bodies. Community and regulatory pressure to move to higher standards of treatment is based on the presumption that a higher standard of treatment is more protective of the environment and society, and thus is more sustainable. This analysis tests that hypothesis for Western Australian conditions. The merits of various wastewater treatment and discharge strategies are examined by quantifying financial costs (capital and operations), and by monetising the wider environmental and social costs and benefits of each option over an expanded planning horizon (30 years). Six technical treatment-disposal options were assessed at a test site, all of which met the fundamental criterion of protecting human health. From a financial perspective, the current business-as-usual option is preferred - it is the least cost solution. However, valuing externalities such as water, greenhouse gases, ecological impacts and community amenity, the status quo is revealed as sub-optimal. Advanced secondary treatment with stream disposal improves water quality and provides overall net benefit to society. All of the other options were net present value (NPV) negative. Sensitivity analysis shows that the favoured option outperforms all of the others under a wide range of financial and externality values and assumptions. Expanding the findings across the state reveals that moving from the identified socially optimal level of treatment to higher (tertiary) levels of treatment would result in a net loss to society equivalent to several hundred million dollars. In other words, everyone benefits from improving treatment to the optimum point. But society, the environment, and the Corporation are all worse off when treatment levels are pushed beyond what is economic and sustainable. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Apatinib treatment in extensive metastatic advanced thymic carcinoma.

    PubMed

    He, Y; Liu, S; E, M; Wang, C; Shi, M; Liu, G; Abiyasi, N

    2018-01-01

    Apatinib is a novel oral, anti-tumor, angiogenic-targeting drug that can selectively target vascular endothelial growth factor receptor-2 (VEGFR-2). In clinical trials, this new tyrosine kinase inhibitor (TKI) has been shown to be an effective and safe treatment for a variety of malignancies. Currently, there is a lack of studies of patients with thymic carcinoma; therefore, we present a case of advanced thymic carcinoma treated with apatinib after chemotherapy failure with multiple lung metastases. This patient has been taking a dose of 500 mg of apatinib per day, and his efficacy has achieved partial response (PR), according to the RECIST 1.1 standard, and progression-free survival (PFS) is 6.3 months at this point. Apatinib will continue as his maintenance treatment. During the treatment, drug-related toxicity and side effects were tolerable. Thus, apatinib may be a meaningful option for the treatment of advanced metastatic thymic carcinoma after chemotherapy failure.

  7. Posterior Tibial Tendon Dysfunction (PTTD)

    MedlinePlus

    ... treatment, surgery may be required. For some advanced cases, surgery may be the only option. Your foot and ankle surgeon will determine the best approach for you. Find an ACFAS Physician Search Search Tools Find an ACFAS Physician: Search by Mail Address ...

  8. Current Status and Future Prospects for Esophageal Cancer Treatment

    PubMed Central

    Kuwano, Hiroyuki

    2016-01-01

    The local control effect of esophagectomy with three-field lymph node dissection (3FLD) is reaching its limit pending technical advancement. Minimally invasive esophagectomy (MIE) by thoracotomy is slowly gaining acceptance due to advantages in short-term outcomes. Although the evidence is slowly increasing, MIE is still controversial. Also, the results of treatment by surgery alone are limiting, and multimodality therapy, which includes surgical and non-surgical treatment options including chemotherapy, radiotherapy, and endoscopic treatment, has become the mainstream therapy. Esophagectomy after neoadjuvant chemotherapy (NAC) is the standard treatment for clinical stages II/III (except for T4) esophageal cancer, whereas chemoradiotherapy (CRT) is regarded as the standard treatment for patients who wish to preserve their esophagus, those who refuse surgery, and those with inoperable disease. CRT is also usually selected for clinical stage IV esophageal cancer. On the other hand, with the spread of CRT, salvage esophagectomy has traditionally been recognized as a feasible option; however, many clinicians oppose the use of surgery due to the associated unfavorable morbidity and mortality profile. In the future, the improvement of each treatment result and the establishment of individual strategies are important although esophageal cancer has many treatment options. PMID:28003586

  9. To ventricular assist devices or not: When is implantation of a ventricular assist device appropriate in advanced ambulatory heart failure?

    PubMed Central

    Cerier, Emily; Lampert, Brent C; Kilic, Arman; McDavid, Asia; Deo, Salil V; Kilic, Ahmet

    2016-01-01

    Advanced heart failure has been traditionally treated via either heart transplantation, continuous inotropes, consideration for hospice and more recently via left ventricular assist devices (LVAD). Heart transplantation has been limited by organ availability and the futility of other options has thrust LVAD therapy into the mainstream of therapy for end stage heart failure. Improvements in technology and survival combined with improvements in the quality of life have made LVADs a viable option for many patients suffering from heart failure. The question of when to implant these devices in those patients with advanced, yet still ambulatory heart failure remains a controversial topic. We discuss the current state of LVAD therapy and the risk vs benefit of these devices in the treatment of heart failure. PMID:28070237

  10. Treatment options for moderate-to-very severe chronic obstructive pulmonary disease.

    PubMed

    Cazzola, Mario; Rogliani, Paola; Ora, Josuel; Matera, Maria Gabriella

    2016-01-01

    The appropriate drug management of COPD is still based on the use of bronchodilators, possibly associated with an anti-inflammatory agent. However, there are still fundamental questions that require clarification to optimise their use and major unmet clinical needs that must be addressed. The advances obtained with the pharmacological options currently consolidated and the different approaches that are often used in an attempt to respond to unmet therapeutic needs are reviewed Expert opinion: In view of the unsatisfactory status of current treatments for COPD, there is an urgent need for alternative and more effective therapeutic approaches that will help to relieve patient symptoms and affect the natural course of COPD, inhibiting chronic inflammation and reversing the disease process or preventing its progression. However, new pharmacologic options have proved difficult to develop. Therefore, it is mandatory to optimize the use of the treatment options at our disposal. However, there are still fundamental questions regarding their use, including the step-up and step-down pharmacological approach, that require clarification to optimise the use of these drugs. It is likely that phenotyping COPD patients would help in identifying the right treatment for each COPD patient and improve the effectiveness of therapies.

  11. Posttraumatic Stress Disorder and Co-Occurring Substance Use Disorders: Advances in Assessment and Treatment

    PubMed Central

    McCauley, Jenna L; Killeen, Therese; Gros, Daniel F.; Brady, Kathleen T.; Back, Sudie E.

    2013-01-01

    Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) are prevalent and frequently co-occur. Comorbid PTSD/SUD is associated with a more complex and costly clinical course when compared with either disorder alone, including increased chronic physical health problems, poorer social functioning, higher rates of suicide attempts, more legal problems, increased risk of violence, worse treatment adherence, and less improvement during treatment. In response, psychosocial treatment options have increased substantially over the past decade and integrated approaches – treatments that address symptoms of both PTSD and SUD concurrently –are fast becoming the preferred model for treatment. This paper reviews the prevalence, etiology and assessment practices as well as advances in the behavioral and pharmacologic treatment of comorbid PTSD and SUDs. PMID:24179316

  12. Immune Checkpoint Inhibitors in the Treatment of Patients with Neuroendocrine Neoplasia.

    PubMed

    Weber, Matthias M; Fottner, Christian

    2018-01-01

    Well-differentiated neuroendocrine neoplasms (NENs) are usually controlled by antiproliferative, local ablative and/or radionuclide therapies, whereas poorly differentiated NENs generally require cytotoxic chemotherapy. However, treatment options for patients with advanced/metastatic high-grade NENs remain limited. Review of the literature and international congress abstracts on the efficacy and safety of immunotherapy by checkpoint inhibition in advanced/metastatic NENs. Evidence points to an important role of immune phenomena in the pathogenesis and treatment of neuroendocrine tumors (NETs). Programmed cell death 1 (PD-1) protein and its ligand are mainly expressed in poorly differentiated NENs. Microsatellite instability and high mutational load are more pronounced in high-grade NENs and may predict response to immunotherapy. Clinical experience of immune checkpoint blockade mainly exists for Merkel cell carcinoma, a high-grade cutaneous neuroendocrine carcinoma (NEC), which has led to approval of the anti-PD-1 antibody avelumab. In addition, there is anecdotal evidence for the efficacy of checkpoint inhibitors in large-cell lung NECs, ovarian NECs and others, including gastroenteropancreatic NENs. Currently, phase II studies investigate PDR001, pembrolizumab, combined durvalumab and tremelimumab, and avelumab treatment in patients with advanced/metastatic NENs. Immune checkpoint inhibitors are a promising therapeutic option, especially in progressive NECs or high-grade NETs with high tumor burden, microsatellite instability, and/or mutational load. © 2018 S. Karger GmbH, Freiburg.

  13. Nonmalignant Diseases and Treatments Associated with Primary Ovarian Failure: An Expanded Role for Fertility Preservation

    PubMed Central

    Hirshfeld-Cytron, Jennifer; Gracia, Clarisa

    2011-01-01

    Abstract Cancer treatments can be detrimental to fertility; recent literature has focused on the efforts of fertility preservation for this patient population. It should be recognized, however, that several nonmalignant medical conditions and therapeutic interventions could be similarly hazardous to fertility. Some of these nonmalignant diseases and their treatments that can adversely impact the reproductive axis are gastrointestinal diseases, rheumatologic disorders, nonmalignant hematologic conditions, neurologic disorders, renal disorders, gynecologic conditions, and metabolic diseases. Their negative effects on reproductive function are only now being appreciated and include impaired ovarian function, endocrine function, or sexual function and inability to carry a pregnancy to term. Complications and comorbidities associated with certain diseases may limit the success of established fertility preservation options. Recent advances in fertility preservation techniques may provide these patients with new options for childbearing. Here, we review several fertility-threatening conditions and treatments, describe current established and experimental fertility preservation options, and present three initiatives that may help minimize the adverse reproductive effects of these medical conditions and treatments by raising awareness of the issues and options: (1) increase awareness among practitioners about the reproductive consequences of specific diseases and treatments, (2) facilitate referral of patients to fertility-sparing or restorative programs, and (3) provide patient education about the risk of infertility at the time of diagnosis before initiation of treatment. PMID:21827325

  14. Nonmalignant diseases and treatments associated with primary ovarian failure: an expanded role for fertility preservation.

    PubMed

    Hirshfeld-Cytron, Jennifer; Gracia, Clarisa; Woodruff, Teresa K

    2011-10-01

    Cancer treatments can be detrimental to fertility; recent literature has focused on the efforts of fertility preservation for this patient population. It should be recognized, however, that several nonmalignant medical conditions and therapeutic interventions could be similarly hazardous to fertility. Some of these nonmalignant diseases and their treatments that can adversely impact the reproductive axis are gastrointestinal diseases, rheumatologic disorders, nonmalignant hematologic conditions, neurologic disorders, renal disorders, gynecologic conditions, and metabolic diseases. Their negative effects on reproductive function are only now being appreciated and include impaired ovarian function, endocrine function, or sexual function and inability to carry a pregnancy to term. Complications and comorbidities associated with certain diseases may limit the success of established fertility preservation options. Recent advances in fertility preservation techniques may provide these patients with new options for childbearing. Here, we review several fertility-threatening conditions and treatments, describe current established and experimental fertility preservation options, and present three initiatives that may help minimize the adverse reproductive effects of these medical conditions and treatments by raising awareness of the issues and options: (1) increase awareness among practitioners about the reproductive consequences of specific diseases and treatments, (2) facilitate referral of patients to fertility-sparing or restorative programs, and (3) provide patient education about the risk of infertility at the time of diagnosis before initiation of treatment.

  15. New advances in erectile technology

    PubMed Central

    Stein, Marshall J.; Lin, Haocheng

    2014-01-01

    New discoveries and technological advances in medicine are rapid. The role of technology in the treatment of erectile dysfunction (ED) will be widened and more options will be available in the years to come. These erectile technologies include external penile support devices, penile vibrators, low intensity extracorporeal shockwave, tissue engineering, nanotechnology and endovascular technology. Even for matured treatment modalities for ED, such as vacuum erectile devices and penile implants, there is new scientific information and novel technology available to improve their usage and to stimulate new ideas. We anticipate that erectile technologies may revolutionize ED treatment and in the very near future ED may become a curable condition. PMID:24489605

  16. Road map to esophagectomy for nurses.

    PubMed

    Logue, Barbara; Griffin, Scott

    2011-08-01

    Esophageal cancer, although considered uncommon in the United States, continues to exhibit increased incidence. Esophageal cancer now ranks seventh among cancers in mortality for men in the United States. Even as treatment continues to advance, the mortality rate remains high, with a 5-year survival rate less than 35%. Esophageal cancer typically is discovered in advanced stages, which reduces the treatment options. When disease is locally advanced, esophagectomy remains the standard for treatment. Surgery remains challenging and complicated. Multiple surgical approaches are available, with the choice determined by tumor location and stage of disease. Recovery is often fraught with complications-both physical and emotional. Nursing care revolves around complex care managing multiple body systems and providing effective education and emotional support for both patients and patients' families. Even after recovery, local recurrence and distant metastases are common. Early diagnosis, surgical advancement, and improvements in postoperative care continue to improve outcomes.

  17. Recognizing Advanced Heart Failure and Knowing Your Options

    MedlinePlus

    ... and Live Our Interactive Cardiovascular Library has detailed animations and illustrations to help you learn about conditions, treatments and procedures related to heart disease and stroke. Popular Articles 1 Understanding Blood Pressure Readings 2 Sodium and Salt 3 Heart Attack Symptoms ...

  18. An update on adjunctive treatment options for bipolar disorder.

    PubMed

    Dean, Olivia M; Gliddon, Emma; Van Rheenen, Tamsyn E; Giorlando, Francesco; Davidson, Sandra K; Kaur, Manreena; Ngo, Trung T; Williams, Lana J

    2018-03-01

    Bipolar disorder is a complex illness often requiring combinations of therapies to successfully treat symptoms. In recent years, there have been significant advancements in a number of therapies for bipolar disorder. It is therefore timely to provide an overview of current adjunctive therapeutic options to help treating clinicians to inform their patients and work towards optimal outcomes. Publications were identified from PubMed searches on bipolar disorder and pharmacotherapy, nutraceuticals, hormone therapy, psychoeducation, interpersonal and social rhythm therapy, cognitive remediation, mindfulness, e-Health and brain stimulation techniques. Relevant articles in these areas were selected for further review. This paper provides a narrative review of adjunctive treatment options and is not a systematic review of the literature. A number of pharmacotherapeutic, psychological and neuromodulation treatment options are available. These have varying efficacy but all have shown benefit to people with bipolar disorder. Due to the complex nature of treating the disorder, combination treatments are often required. Adjunctive treatments to traditional pharmacological and psychological therapies are proving useful in closing the gap between initial symptom remission and full functional recovery. Given that response to monotherapy is often inadequate, combination regimens for bipolar disorder are typical. Correspondingly, psychiatric research is working towards a better understanding of the disorder's underlying biology. Therefore, treatment options are changing and adjunctive therapies are being increasingly recognized as providing significant tools to improve patient outcomes. Towards this end, this paper provides an overview of novel treatments that may improve clinical outcomes for people with bipolar disorder. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Present and future drug treatment for Parkinson's disease

    PubMed Central

    Schapira, A

    2005-01-01

    Considerable advances made in defining the aetiology, pathogenesis, and pathology of Parkinson's disease (PD) have resulted in the development and rapid expansion of the pharmacopoeia available for treatment. Anticholinergics were used before the introduction of levodopa which is now the drug most commonly used. Dopamine agonists are effective when used alone or as an adjunct to levodopa, while monoamine oxidase B inhibitors improve motor function in early and advanced PD. However, treatment mainly addresses the dopaminergic features of the disease and leaves its progressive course unaffected; the drug treatment available for the management of non-motor symptoms is limited. This article seeks to set current treatment options in context, review emerging and novel drug treatments for PD, and assess the prospects for disease modification. Surgical therapies are not considered. PMID:16227533

  20. Amyloidosis: Pathogenesis and New Therapeutic Options

    PubMed Central

    Merlini, Giampaolo; Seldin, David C.; Gertz, Morie A.

    2011-01-01

    The systemic amyloidoses are a group of complex diseases caused by tissue deposition of misfolded proteins that results in progressive organ damage. The most common type, immunoglobulin light chain amyloidosis (AL), is caused by clonal plasma cells that produce misfolded light chains. The purpose of this review is to provide up-to-date information on diagnosis and treatment options for AL amyloidosis. Early, accurate diagnosis is the key to effective therapy, and unequivocal identification of the amyloidogenic protein may require advanced technologies and expertise. Prognosis is dominated by the extent of cardiac involvement, and cardiac staging directs the choice of therapy. Treatment for AL amyloidosis is highly individualized, determined on the basis of age, organ dysfunction, and regimen toxicities, and should be guided by biomarkers of hematologic and cardiac response. Alkylator-based chemotherapy is effective in almost two thirds of patients. Novel agents are also active, and trials are ongoing to establish their optimal use. Treatment algorithms will continue to be refined through controlled trials. Advances in basic research have led to the identification of new drug targets and therapeutic approaches, which will be integrated with chemotherapy in the future. PMID:21483018

  1. Integrated treatment options for male perpetrators of intimate partner violence.

    PubMed

    Crane, Cory A; Easton, Caroline J

    2017-01-01

    Male-to-female intimate partner violence remains a worldwide public health issue with adverse physical and psychological consequences for victims, perpetrators and children. Personality disorders, addiction, trauma and mood symptoms are established risk factors for intimate partner violence perpetration and factor prominently into a recovery-oriented treatment approach. We reviewed the partner violence literature for detailed reports of traditional as well as innovative, integrated treatment approaches. Empirically based recommendations for intervention programs and the policies that guide intervention efforts are offered. Nascent research suggests that integrated treatment models utilising a holistic approach to account for psychological comorbidity and interventions that involve a motivational interviewing component appear promising in terms of significantly improving intimate partner violence treatment compliance and reducing subsequent acts of physical partner violence. Further, methodologically rigorous research is required to fully assess the benefits of traditional and integrated treatment options. We have advanced several recommendations, including the development of and exclusive reliance upon empirically supported treatments, conducting a thorough risk and needs assessment of the offender and the immediate family to facilitate appropriate treatment referrals, integrating content to foster the offender's internal motivation to change maladaptive behaviours, and attempting to minimise offender treatment burdens through the strategic use of integrated treatment models. Intimate partner violence is a complicated and nuanced problem that is perpetrated by a heterogeneous population and requires greater variability in integrated treatment options. [Crane CA, Easton CJ. Integrated treatment options for male perpetrators of intimate partner violence. Drug Alcohol Rev 2017;36:24-33]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  2. Treatment of early Parkinson's disease.

    PubMed

    Pahwa, Rajesh; Lyons, Kelly E

    2014-08-01

    This review summarizes currently available treatment options and treatment strategies, investigational treatments, and the importance of exercise for early Parkinson's disease. The available treatment options for early Parkinson's disease have changed little in the past decade and include carbidopa/levodopa, dopamine agonists, and monoamine oxidase type B (MAO-B) inhibitors. However, we discuss changes in treatment strategies, including dosing and the use of combination therapy used in an attempt to reduce or delay the appearance of motor complications and other adverse events. We will also review several investigational treatments that have shown promise for the treatment of early Parkinson's disease, including a new extended release formulation of carbidopa/levodopa (IPX066), safinamide which inhibits MAO-B, dopamine uptake and glutamate and pardoprunox which is a 5HT-1A agonist and a partial dopamine agonist. Finally, we discuss recent studies focusing on exercise as an important component in the management of early Parkinson's disease. Advances in the management of early Parkinson's disease include evolving treatment strategies, new investigational treatments, and earlier implementation of various forms of exercise.

  3. New Basal Insulins: a Clinical Perspective of Their Use in the Treatment of Type 2 Diabetes and Novel Treatment Options Beyond Basal Insulin.

    PubMed

    Frias, Patrick F; Frias, Juan Pablo

    2017-08-18

    The purpose of this review was to review advances in basal insulin formulations and new treatment options for patients with type 2 diabetes not achieving glycemic targets despite optimized basal insulin therapy. Advances in basal insulin formulations have resulted in products with increasingly favorable pharmacokinetic and pharmacodynamic properties, including flatter, peakless action profiles, less inter- and intra-patient variability, and longer duration of activity. These properties have translated to significantly reduced risk of hypoglycemia (particularly during the night) compared with previous generation basal insulins. When optimized basal insulin therapy is not sufficient to obtain or maintain glycemic goals, various options exist to improve glycemic control, including intensification of insulin therapy with the addition of prandial insulin or changing to pre-mixed insulin and, more recently, the addition of a GLP-1 receptor agonist, either as a separate injection or as a component of one of the new fixed-ratio combinations of a basal insulin and GLP-1 RA. New safer and often more convenient basal insulins and fixed ratio combinations containing basal insulin (and GLP-1 receptor agonist) are available today for patients with type 2 diabetes not achieving glycemic goals. Head-to-head studies comparing the latest generation basal insulins are underway, and future studies assessing the fixed-ratio combinations will be important to better understand their differentiating features.

  4. Advanced Stent Graft Treatment of Venous Stenosis Affecting Hemodialysis Vascular Access: Case Illustrations

    PubMed Central

    Patel, Darshan; Ray, Charles E.; Lokken, R. Peter; Bui, James T.; Lipnik, Andrew J.; Gaba, Ron C.

    2016-01-01

    Surgically placed dialysis access is an important component of dialysis replacement therapy. The vast majority of patients undergoing dialysis will have surgically placed accesses at some point in the course of their disease, and for many patients these accesses may represent their definitive renal replacement option. Most, if not all, arteriovenous fistulae and grafts will require interventions at some point in time. Percutaneous angioplasty is the typical first treatment performed for venous stenoses, with stents and stent grafts being reserved for patients in whom angioplasty and surgical options are exhausted. In some salvage situations, stent graft placement may be the only or best option for patients. This article describes, using case illustrations, placement of stent grafts in such patients; a focus will also be made on the techniques utilized in such salvage situations. PMID:27011426

  5. Phase II drugs currently being investigated for the treatment of hypogonadism.

    PubMed

    Udedibia, Emeka; Kaminetsky, Jed

    2014-12-01

    Hypogonadism is the most common endocrine disorder, which affects men of all age groups. Recent shifts in public awareness, increased screening and recognition of symptoms and updated diagnostic criteria have led to an increase in men diagnosed as hypogonadal, including middle-aged and older men who previously would have been considered eugonadal. The increase in testosterone replacement therapy (TRT) has paralleled an increase in advancements of treatment options. Although current therapies are highly efficacious for many men, there remains a need for newer therapies that are more cost-effective, preserve ease of use and administration, mitigate undesirable effects and closely mimic physiological levels of testosterone. In this review, the authors discuss current TRTs and therapies in development for the treatment of hypogonadism. The focus is on therapies under Phase II investigation or those who have recently completed Phase II study. With several new therapies in development, the authors expect advancements in achieving treatment benchmarks that meet the needs of the individual symptomatic hypogonadal male. Increased public awareness of hypogonadism and TRT has led to a welcomed expansion in the choice of TRT options. These include new delivery systems, formulations, routes of administration and non-testosterone modalities.

  6. Impact of a decision aid on surrogate decision-makers' perceptions of feeding options for patients with dementia.

    PubMed

    Snyder, E Amanda; Caprio, Anthony J; Wessell, Kathryn; Lin, Feng Chang; Hanson, Laura C

    2013-02-01

    In advanced dementia, feeding problems are nearly universal, and families face difficult decisions about feeding options. Initial interviews for a randomized trial were used to describe surrogates' perceptions of feeding options, and to determine whether a decision aid on feeding options in advanced dementia would improve knowledge, reduce expectation of benefit from tube feeding, and reduce conflict over treatment choices for persons with advanced dementia. Semistructured interview with prestudy and poststudy design for surrogates in the intervention group. Twenty-four skilled nursing facilities across North Carolina participating in a cluster randomized trial. Two hundred and fifty-five surrogate decision makers for nursing home residents with advanced dementia and feeding problems, in control (n = 129) and intervention (n = 126) groups. For intervention surrogates only, an audiovisual-print decision aid provided information on dementia, feeding problems in dementia, advantages and disadvantages of feeding tubes or assisted oral feeding options, and the role of surrogates in making these decisions. The interview included open-ended items asking surrogates to report advantages and disadvantages of tube feeding and assisted oral feeding. Knowledge of feeding options was measured with 19 true/false items and items measuring expectation of benefit from tube feeding. Surrogates reported which of these two feeding options they preferred for the person with dementia, and how confident they were in this choice; their level of conflict about the choice was measured using the decisional conflict scale. Before the decision aid, surrogates described advantages and disadvantages of assisted oral feeding and tube feeding in practical, ethical, and medical terms. After review of the decision aid, intervention surrogates had improved knowledge scores (15.5 vs 16.8; P < .001), decreased expectation of benefits from tube feeding (2.73 vs 2.32; P = .001), and reduced decisional conflict (2.24 vs 1.91; P < .001). Surrogates preferred assisted oral feeding initially and reported more certainty about this choice after the decision aid. A structured decision aid can be used to improve decision making about feeding options in dementia care. Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

  7. Impact of a Decision Aid on Surrogate Decision-makers’ Perceptions of Feeding Options for Patients with Dementia

    PubMed Central

    Snyder, E. Amanda; Caprio, Anthony J.; Wessell, Kathryn; Lin, Feng Chang; Hanson, Laura C.

    2012-01-01

    Objective In advanced dementia, feeding problems are nearly universal, and families face difficult decisions about feeding options. Initial interviews for a randomized trial were used to describe surrogates’ perceptions feeding options, and to determine if a decision aid on feeding options in advanced dementia would improve knowledge, reduce expectation of benefit from tube feeding, and reduce conflict over treatment choices for persons with advanced dementia. Design Semi-structured interview with pre-post study design for surrogates in the intervention group. Setting Twenty-four skilled nursing facilities across North Carolina participating in a cluster randomized trial. Participants Two hundred fifty-five surrogate decision-makers for nursing home residents with advanced dementia and feeding problems, in control (n=129) and intervention (n=126) groups. Intervention For intervention surrogates only, an audiovisual-print decision aid provided information on dementia, feeding problems in dementia, advantages and disadvantages of feeding tubes or assisted oral feeding options and the role of surrogates in making these decisions. Measurements The interview included open-ended items asking surrogates to report advantages and disadvantages of tube feeding and assisted oral feeding. Knowledge of feeding options was measured with 19 true-false items, and items measuring expectation of benefit from tube feeding. Surrogates reported which of these two feeding options they preferred for the person with dementia, and how confident they were in this choice; their level of conflict about the choice was measured using the Decisional Conflict Scale. Results Prior to the decision aid, surrogates described advantages and disadvantages of assisted oral feeding and tube feeding in practical, ethical and medical terms. After review of the decision aid, intervention surrogates had improved knowledge scores (15.5 vs. 16.8; p<0.001), decreased expectation of benefits from tube feeding (2.73 vs. 2.32; p = 0.001) and reduced decisional conflict (2.24 vs. 1.91, p<0.001). Surrogates preferred assisted oral feeding initially, and reported more certainty about this choice after the decision aid. Conclusion A structured decision aid can be used to improve decision-making about feeding options in dementia care. PMID:23273855

  8. Is whole gland salvage cryotherapy effective as palliative treatment of haematuria in patients with locally advanced prostate cancer? Results of a preliminary case series

    PubMed Central

    Mucciardi, Giuseppe; Galì, Alessandro; Pappalardo, Rosa; Lembo, Francesco; Anastasi, Giuseppina; Butticè, Salvatore; Ascenti, Giorgio; Lugnani, Franco

    2015-01-01

    Objectives: Locally advanced prostate cancer may cause several complications such as haematuria, bladder outlet obstruction, and renal failure due to the ureteral obstruction. Various treatments have been suggested, including radiotherapy, antifibrinolytics, bladder irrigation with alum solution, transurethral surgery and angioembolization, none of which have proven effectiveness. In the last years cryoablation has become a valid therapeutic option for prostate cancer. In our experience we used this ‘new’ technique as haemostatic therapy. Methods: We selected four patients with gross haematuria affected by locally advanced hormone refractory prostate cancer, who had already been treated with primary radiotherapy. We used third-generation cryotherapy: under ultrasonographic guidance, we inserted six cryoprobes, two in each of the vascular pedicles reaching at least −60°C, and three thermometers. We then induced two freeze–thaw cycles. Results: After the operation the haematuria stopped in all patients and at 9-month follow up we observed a mean of four red cells (range three to five) in the urinary sediment with no evidence of bacteriuria. Prostate volume, prostate-specific antigen and postmicturition residue were significantly reduced. Qmax improved significantly too. Conclusion: Our experience has given us good results with minimal intra- and postoperative complications. We think that haemostatic cryotherapy as a palliative approach for locally advanced prostate cancer could represent a valid treatment option and more consideration could be given to its use. PMID:26425138

  9. Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma.

    PubMed

    Ito, Yasuhiro; Onoda, Naoyoshi; Ito, Ken-Ichi; Sugitani, Iwao; Takahashi, Shunji; Yamaguchi, Iku; Kabu, Koki; Tsukada, Katsuya

    2017-09-01

    Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan, even though vandetanib for MTC and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory differentiated thyroid cancer (DTC). An uncontrolled, open-label, multicenter, single-arm, Phase 2 clinical study was conducted to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC. Japanese patients with histologically confirmed ATC and locally advanced or metastatic MTC were enrolled from April to September 2014. The primary endpoint was to evaluate the safety of sorafenib. Treatment efficacy variables including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and maximum reduction in tumor size were evaluated as secondary endpoints. Patients received sorafenib 400 mg orally twice daily on a continuous basis and then continued treatment until the occurrence of disease progression, unacceptable toxicity, or withdrawal of consent. A total of 20 patients were screened, and 18 (8 with MTC and 10 with ATC) were enrolled. The most common drug-related adverse events were palmar-plantar erythrodysesthesia (72%), alopecia (56%), hypertension (56%), and diarrhea (44%). In the ATC patients, median PFS was 2.8 months [confidence interval 0.7-5.6], and median OS was 5.0 months [confidence interval 0.7-5.7]; ORR and DCR were 0% and 40%, respectively. In the MTC population, neither median PFS nor OS had been reached at the time of this analysis; ORR was 25% and DCR was 75%. The toxicities reported in this study were consistent with the known safety profile of sorafenib. Sorafenib seems to be effective in the treatment of advanced MTC but not ATC, and could be a new treatment option for locally advanced or metastatic MTC and radioactive iodine-refractory DTC.

  10. Rectal cancer with synchronous liver metastases: Do we have a clear direction?

    PubMed

    Pathak, S; Nunes, Q M; Daniels, I R; Smart, N J; Poston, G J; Påhlman, L

    2015-12-01

    Rectal cancer is a common entity and often presents with synchronous liver metastases. There are discrepancies in management guidelines throughout the world regarding the treatment of advanced rectal cancer, which are further compounded when it presents with synchronous liver metastases. The following article examines the evidence regarding treatment options for patients with synchronous rectal liver metastases and suggests potential treatment algorithms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Managing the maxillary partially edentulous patient with extensive anterior tooth loss and advanced periodontal disease using a removable partial denture: a clinical report.

    PubMed

    Ma, Polly S; Brudvik, James S

    2008-10-01

    The treatment modality, a continuous occlusal rest removable partial denture, not only restored missing teeth but also stabilized the remaining dentition in a patient with advanced periodontal attachment loss. By engaging the guiding planes at the mesial surfaces of the abutments anteriorly and also the distal surfaces of the abutments posteriorly, the remaining teeth, with varying amounts of mobility, were splinted together by the framework. This conservative treatment option allows flexibility for easy repair during the life span of the prosthesis.

  12. Medical treatment of advanced non-small cell lung cancer in elderly patients: a review of the role of chemotherapy and targeted agents.

    PubMed

    Meoni, Giulia; Cecere, Fabiana Letizia; Lucherini, Elisa; Di Costanzo, Francesco

    2013-07-01

    Lung cancer is the leading cause of cancer related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of all cases. Half of the patients at diagnosis of NSCLC are over seventy years old; therefore, the elderly represent a large subgroup of patients affected by advanced NSCLC in our clinical practice. Nevertheless, the elderly are under-represented in clinical trials. Given the fact that old age is frequently associated with several comorbidities, poor general conditions and physiologic reduction in organ function, clinicians must carefully choose the best treatment option for elderly patients with advanced NSCLC, always taking into account the expected risks and benefits. In this paper we perform a review of literature evidence regarding the medical treatment of elderly patients affected by advanced NSCLC, encompassing single-agent chemotherapy, doublet chemotherapy and targeted agents. We conclude that single-agent chemotherapy with a third generation agent (vinorelbine, taxanes, gemcitabine) represents a valid treatment option for elderly patients who are not eligible for a combination chemotherapy due to clinical features such as comorbidities, poor performance status and inadequate organ function. Platinum-based doublet chemotherapy shows similar efficacy in elderly patients as compared to their younger counterpart, despite greater treatment related toxicity and it is indicated in elderly patients with ECOG PS: 0-2, adequate organ function and no major comorbidities. Elderly patients affected by epidermal growth factor receptor (EGFR) mutated NSCLC benefit mostly from a tyrosine kinase inhibitor of EGFR (erlotinib, gefitinib) which is associated with a good toxicity profile. Currently there are no available data to strongly support the use of bevacizumab in combination with first line chemotherapy in the treatment of older adults. Elderly patients affected by NSCLC harboring the EML4-ALK translocation could benefit mostly from a treatment with an oral inhibitor of such a rearrangement (crizotinib). Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Prophylaxis versus treatment: Is there a better way to manage radiotherapy-induced nausea and vomiting?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Horiot, Jean-Claude

    Nausea and vomiting are two of the most distressing side effects of radiotherapy and cytotoxic drugs, which currently are often combined to treat moderately advanced and advanced solid tumors. Inadequate control of these symptoms may result in significant patient suffering and decrease in the patient's quality of life, which has been shown to decrease patients' compliance to treatment, with potential impact on disease outcome. It is, therefore, important that radiation oncologists recognize the need for adequate prophylactic treatment of radiation-induced nausea and vomiting (RINV) to avoid the detrimental effects on patients' quality of life, and optimize chances for cure. Themore » 5-hydroxytryptamine type 3 (5-HT{sub 3})-receptor antagonists have been proved to provide effective antiemetic therapy in patients undergoing highly emetogenic radiotherapy. Nevertheless, several large surveys have shown that optimal treatments are not always used. Hence, a risk exists that waiting for RINV symptoms rather than prescribing prophylactic antiemetic treatment may lead to increased patient suffering, poorer disease control, and less cost-effective therapy options. Prophylactic management with an effective 5-HT{sub 3}-receptor antagonist should offer a better treatment option for patients at high to moderate risk of RINV. Adequate control of RINV should contribute to patient compliance to treatment, improved therapy outcomes, and decreased burdens on nursing and health care resources.« less

  14. Successful treatment with pazopanib plus PD-1 inhibitor and RAK cells for advanced primary hepatic angiosarcoma: a case report.

    PubMed

    Qiao, Yu; Yang, Jihong; Liu, Lili; Zeng, Yixin; Ma, Jie; Jia, Jing; Zhang, Li; Li, Xiaoguang; Wu, Peihong; Wang, Wenchao; Liu, Dongge; Chen, Huan; Zhao, Yunbo; Xi, Huan; Wang, Yao

    2018-02-21

    Primary hepatic angiosarcoma (PHA) is a rare and aggressive solid tumor, with high rates of local recurrence and distant metastasis, and poor prognosis. There are no established treatment guidelines for PHA. A 78-year-old asymptomatic man with PHA that was successfully treated with pazopanib plus PD-1 inhibitor and RetroNectin-activated killer cells (RAK cells). After one month of treatment, there was a clear reduction in the size and number of the liver metastases; and after nearly 15 months, most of the lesions were stable, no new lesions had developed, and the side effect of treatment was minor. Pazopanib, PD-1 inhibitor and RAK cells could serve as a potential option for the treatment of advanced PHA.

  15. Bariatric embolization: a new and effective option for the obese patient?

    PubMed

    Weiss, Clifford R; Kathait, Anjaneya S

    2017-04-01

    Obesity is a public health epidemic in the United States, which results in significant morbidity, mortality, and cost to the healthcare system. Despite advancements in traditional therapeutic options for the obese patients, there is a treatment gap for patients in whom lifestyle modifications alone have not been successful, but for whom bariatric surgery is not a suitable option. Areas covered: This treatment gap needs to be addressed and thus, complimentary or alternative treatments to lifestyle changes and surgery are urgently needed. Recent evidence suggests that embolization of the gastric fundus ('Bariatric Embolization'), which is predominantly supplied by the left gastric artery, may affect energy homeostasis by decreasing ghrelin production. The purpose of this special report is to discuss the background, rationale and latest data on this topic, as well as provide the latest data from the ongoing BEAT Obesity clinical trial. Expert commentary: A multipronged approach is essential in the treatment of obesity. Bariatric embolization looks to treat the hormonal imbalances which contribute to obesity. If proven successful in the long-term, bariatric embolization represents a potential minimally invasive approach to treat obesity offered by interventional radiologists.

  16. Stereotactic Body Radiotherapy in the Management of Oligometastatic Disease.

    PubMed

    Ahmed, Kamran A; Torres-Roca, Javier F

    2016-01-01

    The treatment of oligometastatic disease has become common as imaging techniques have advanced and the management of systemic disease has improved. Use of highly targeted, hypofractionated regimens of stereotactic body radiotherapy (SBRT) is now a primary management option for patients with oligometastatic disease. The properties of SBRT are summarized and the results of retrospective and prospective studies of SBRT use in the management of oligometastases are reviewed. Future directions of SBRT, including optimizing dose and fractionation schedules, are also discussed. SBRT can deliver highly conformal, dosed radiation treatments for ablative tumors in a few treatment sessions. Phase 1/2 trials and retrospective institutional results support use of SBRT as a treatment option for oligometastatic disease metastasized to the lung, liver, and spine, and SBRT offers adequate toxicity profiles with good rates of local control. Future directions will involve optimizing dose and fractionation schedules for select histologies to improve rates of local control while limiting toxicity to normal structures. SBRT offers an excellent management option for patients with oligometastases. However, additional research is still needed to optimize dose and fractionation schedules.

  17. Safety, Efficacy, and Patient Acceptability of Everolimus in the Treatment of Breast Cancer.

    PubMed

    Lousberg, Laurence; Jerusalem, Guy

    2016-01-01

    Everolimus combined with exemestane is an important treatment option for patients suffering from estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer (ABC) who have been previously treated with a nonsteroidal aromatase inhibitor (NSAI). After presentation of phase III registration trial BOLERO-2, several phase IIIb trials have been started to evaluate this regimen in a more real-world setting. Here, we review the efficacy and safety data published or presented at selected international meetings. These studies confirmed the outcome observed in the BOLERO-2 trial. Patient acceptance rate is also discussed by focusing on the permanent everolimus discontinuation rate in these trials. Factors influencing the safety profile are also reported, including the impact of age. The optimal sequence of combined therapy approaches associating targeted and endocrine therapy (ET) has yet to be determined as new treatment options such as cyclin-dependent kinase inhibitors become available. However, everolimus-exemestane remains an important treatment option with a major impact on progression-free survival (PFS) and an acceptable safety profile.

  18. Safety, Efficacy, and Patient Acceptability of Everolimus in the Treatment of Breast Cancer

    PubMed Central

    Lousberg, Laurence; Jerusalem, Guy

    2016-01-01

    Everolimus combined with exemestane is an important treatment option for patients suffering from estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer (ABC) who have been previously treated with a nonsteroidal aromatase inhibitor (NSAI). After presentation of phase III registration trial BOLERO-2, several phase IIIb trials have been started to evaluate this regimen in a more real-world setting. Here, we review the efficacy and safety data published or presented at selected international meetings. These studies confirmed the outcome observed in the BOLERO-2 trial. Patient acceptance rate is also discussed by focusing on the permanent everolimus discontinuation rate in these trials. Factors influencing the safety profile are also reported, including the impact of age. The optimal sequence of combined therapy approaches associating targeted and endocrine therapy (ET) has yet to be determined as new treatment options such as cyclin-dependent kinase inhibitors become available. However, everolimus–exemestane remains an important treatment option with a major impact on progression-free survival (PFS) and an acceptable safety profile. PMID:28096680

  19. Advances in Merkel cell carcinoma from a pathologist's perspective.

    PubMed

    Barksdale, Sarah Kay

    2017-10-01

    Merkel cell carcinoma (MCC) is a rarely made but potentially devastating diagnosis. While local disease might be cured by surgery and radiotherapy, advanced disease is usually rapidly progressive and fatal. Until very recently, the only approach to metastatic MCC was cytotoxic chemotherapy with results so disappointing that current treatment guidelines discourage its use and recommend clinical trial as a more viable treatment option. Fortunately, recent advances in the understanding of the molecular pathogenesis of this tumour have produced a wide variety of experimental treatments for MCC, some of which are quite promising. The most current information regarding the diagnosis, staging, management of this tumour is briefly presented as well as new insights into the molecular basis of MCC and therapeutic approaches to MCC. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

  20. Efficacy, safety, and patient preference of monoamine oxidase B inhibitors in the treatment of Parkinson’s disease

    PubMed Central

    Robottom, Bradley J

    2011-01-01

    Parkinson’s disease (PD) is the second most common neurodegenerative disease and the most treatable. Treatment of PD is symptomatic and generally focuses on the replacement or augmentation of levodopa. A number of options are available for treatment, both in monotherapy of early PD and to treat complications of advanced PD. This review focuses on rasagiline and selegiline, two medications that belong to a class of antiparkinsonian drugs called monoamine oxidase B (MAO-B) inhibitors. Topics covered in the review include mechanism of action, efficacy in early and advanced PD, effects on disability, the controversy regarding disease modification, safety, and patient preference for MAO-B inhibitors. PMID:21423589

  1. Efficacy, safety, and patient preference of monoamine oxidase B inhibitors in the treatment of Parkinson's disease.

    PubMed

    Robottom, Bradley J

    2011-01-20

    Parkinson's disease (PD) is the second most common neurodegenerative disease and the most treatable. Treatment of PD is symptomatic and generally focuses on the replacement or augmentation of levodopa. A number of options are available for treatment, both in monotherapy of early PD and to treat complications of advanced PD. This review focuses on rasagiline and selegiline, two medications that belong to a class of antiparkinsonian drugs called monoamine oxidase B (MAO-B) inhibitors. Topics covered in the review include mechanism of action, efficacy in early and advanced PD, effects on disability, the controversy regarding disease modification, safety, and patient preference for MAO-B inhibitors.

  2. Budget impact analysis of everolimus for the treatment of hormone receptor positive, human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer in the United States.

    PubMed

    Xie, Jipan; Diener, Melissa; De, Gourab; Yang, Hongbo; Wu, Eric Q; Namjoshi, Madhav

    2013-01-01

    To estimate the budget impact of everolimus as the first and second treatment option after letrozole or anastrozole (L/A) failure for post-menopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer (ABC). Pharmacy and medical budget impacts (2011 USD) were estimated over the first year of everolimus use in HR+, HER2- ABC from a US payer perspective. Epidemiology data were used to estimate target population size. Pre-everolimus entry treatment options included exemestane, fulvestrant, and tamoxifen. Pre- and post-everolimus entry market shares were estimated based on market research and assumptions. Drug costs were based on wholesale acquisition cost. Patients were assumed to be on treatment until progression or death. Annual medical costs were calculated as the average of pre- and post-progression medical costs weighted by the time in each period, adjusted for survival. One-way and two-way sensitivity analyses were conducted to assess the model robustness. In a hypothetical 1,000,000 member plan, 72 and 159 patients were expected to be candidates for everolimus treatment as first and second treatment option, respectively, after L/A failure. The total budget impact for the first year post-everolimus entry was $0.044 per member per month [PMPM] (pharmacy budget: $0.058 PMPM; medical budget: -$0.014 PMPM), assuming 10% of the target population would receive everolimus. The total budget impacts for the first and second treatment options after L/A failure were $0.014 PMPM (pharmacy budget: $0.018; medical budget: -$0.004) and $0.030 PMPM (pharmacy budget: $0.040; medical budget: -$0.010), respectively. Results remained robust in sensitivity analyses. Assumptions about some model input parameters were necessary and may impact results. Increased pharmacy costs for HR+, HER2- ABC following everolimus entry are expected to be partially offset by reduced medical service costs. Pharmacy and total budget increases were modest.

  3. Neuropathic pain and SCI: Identification and treatment strategies in the 21st century.

    PubMed

    Hatch, Maya N; Cushing, Timothy R; Carlson, Gregory D; Chang, Eric Y

    2018-01-15

    Pain is a common complication in patients following spinal cord injury (SCI), with studies citing up to 80% of patients reporting some form of pain. Neuropathic pain (NP) makes up a substantial percentage of all pain symptoms in patients with SCI and is often complex. Given the high prevalence of NP in patients with SCI, proper identification and treatment is imperative. Indeed, identification of pain subtypes is a vital step toward determining appropriate treatment. A variety of pharmacological and non-pharmacological treatments can be undertaken including antiepileptics, tricyclic antidepressants, opioids, transcranial direct current stimulation, and invasive surgical procedures. Despite all the available treatment options and advances in the field of SCI medicine, providing adequate treatment of NP after SCI continues to be challenging. It is therefore extremely important for clinicians to have a strong foundation in the identification of SCI NP, as well as an understanding of appropriate treatment options. Here, we highlight the definitions and classification tools available for NP identification, and discuss current treatment options. We hope that this will not only provide a better understanding of NP for physicians in various subspecialties, but that it will also help guide future research on this subject. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Pediatric Traumatic Brain Injury and Autism: Elucidating Shared Mechanisms

    PubMed Central

    Singh, Rahul; Nguyen, Linda; Motwani, Kartik; Swatek, Michelle

    2016-01-01

    Pediatric traumatic brain injury (TBI) and autism spectrum disorder (ASD) are two serious conditions that affect youth. Recent data, both preclinical and clinical, show that pediatric TBI and ASD share not only similar symptoms but also some of the same biologic mechanisms that cause these symptoms. Prominent symptoms for both disorders include gastrointestinal problems, learning difficulties, seizures, and sensory processing disruption. In this review, we highlight some of these shared mechanisms in order to discuss potential treatment options that might be applied for each condition. We discuss potential therapeutic and pharmacologic options as well as potential novel drug targets. Furthermore, we highlight advances in understanding of brain circuitry that is being propelled by improved imaging modalities. Going forward, advanced imaging will help in diagnosis and treatment planning strategies for pediatric patients. Lessons from each field can be applied to design better and more rigorous trials that can be used to improve guidelines for pediatric patients suffering from TBI or ASD. PMID:28074078

  5. How I manage patients with Fanconi anaemia.

    PubMed

    Dufour, Carlo

    2017-07-01

    Fanconi Anaemia is a rare, genetic heterogeneous multisystem disease that is the most common congenital syndrome of marrow failure. Twenty genes have been reported to cause the disease. Remarkable progress has been made over the last 20 years in the understanding of the genetic and pathophysiological mechanisms. Unfortunately, these advances have not been completely paralleled by advances in medical treatment, where the most important component remains stem cell transplantation. This therapy, although contributing to long-term negative effects, such as increased occurrence of late malignancies, is the only current option capable of prolonging the survival of patients. In spite of relevant recent progress in matched unrelated donor transplants, the largest studies with longer follow-up still show a superiority of matched sibling donor transplants with a success rate, in selected cohorts, of over 90%. This article reviews different aspects of the disease, including genetics, diagnosis and treatment options, with special focus on stem cell transplantation, comprehensive post-diagnosis management, decision-making processes and long-term follow-up. © 2017 John Wiley & Sons Ltd.

  6. Conservative care as a treatment option for patients aged 75 years and older with CKD stage V: a National survey in the Netherlands.

    PubMed

    Susanto, Christopher; Kooman, J; Courtens, A M; Konings, C J A M

    2018-01-01

    Conservative care for patients aged 75 years and older with CKD stage 5 as a treatment option besides dialysis was proposed officially in the Netherlands in October 2016. This national survey showed the current implementation of this option in Netherlands nephrology departments. A web-based survey was sent to medical managers of 60 nephrology departments in the Netherlands in August 2016. Twenty-one medical managers (35%) completed the survey. The term "conservative care" is frequently used and well known. The estimated number of patients in whom the decision for maximal conservative care was made in 2015 was 310 of 2249 patients with CKD stage 5 age 75 years and older (range 5-50 patients per department). 164 patients became symptomatic and received no dialysis. There is no official registration for this treatment option and patient category. The practice patterns vary widely. Only one of 21 respondents reported a conservative care outpatient clinic. Formal training or education regarding conservative care is not available in most of departments. 95% of respondents discussed this treatment option with their patients. General practitioners are always being informed about their patient's decision. Their main role is providing or organizing palliative care support at the end of life and discussing advance care planning. Most respondents (86%) considered to include their patients in a prospective multicentre observational study, conservative care versus dialysis. Conservative care as a treatment option for patients with CKD stage 5 aged 75 years and older is well established. The practice patterns are varied in the Netherlands. Follow-up studies are needed to see whether the new multidisciplinary guideline facilitates harmonization of practice pattern. Funding is needed to optimize the implementation of conservative care.

  7. Thermal plasma technology for the treatment of wastes: a critical review.

    PubMed

    Gomez, E; Rani, D Amutha; Cheeseman, C R; Deegan, D; Wise, M; Boccaccini, A R

    2009-01-30

    This review describes the current status of waste treatment using thermal plasma technology. A comprehensive analysis of the available scientific and technical literature on waste plasma treatment is presented, including the treatment of a variety of hazardous wastes, such as residues from municipal solid waste incineration, slag and dust from steel production, asbestos-containing wastes, health care wastes and organic liquid wastes. The principles of thermal plasma generation and the technologies available are outlined, together with potential applications for plasma vitrified products. There have been continued advances in the application of plasma technology for waste treatment, and this is now a viable alternative to other potential treatment/disposal options. Regulatory, economic and socio-political drivers are promoting adoption of advanced thermal conversion techniques such as thermal plasma technology and these are expected to become increasingly commercially viable in the future.

  8. Pathways to Genome-targeted Therapies in Serous Ovarian Cancer.

    PubMed

    Axelrod, Joshua; Delaney, Joe

    2017-07-01

    Genome sequencing technologies and corresponding oncology publications have generated enormous publicly available datasets for many cancer types. While this has enabled new treatments, and in some limited cases lifetime management of the disease, the treatment options for serous ovarian cancer remain dismal. This review summarizes recent advances in our understanding of ovarian cancer, with a focus on heterogeneity, functional genomics, and actionable data.

  9. Development of an intervention to support patients and clinicians with advanced lung cancer when considering systematic anticancer therapy: protocol for the PACT study.

    PubMed

    Anagnostou, Despina; Sivell, Stephanie; Noble, Simon; Lester, Jason; Byrne, Anthony; Sampson, Catherine; Longo, Mirella; Nelson, Annmarie

    2017-07-12

    Patient-centred care is essential to the delivery of healthcare; however, this necessitates direct patient involvement in clinical decision-making and can be challenging for patients diagnosed with advanced non-small cell lung cancer where there may be misunderstanding of the extent of disease, prognosis and aims of treatment. In this context, decisions are complex and there is a need to balance the risks and benefits, including treatment with palliative intent. The aim of the PACT study is to identify the information and decision support needs of patients, leading to the development of an intervention to support patients with advanced lung cancer when considering treatment options. PACT is a five-stage, multimethod and multicentre study. Participants : Patients and health professionals will be recruited from three health boards. Methods : Non-participant observation of multidisciplinary team meetings (n=12) will be used to determine patients' allocation to treatment pathways (stage I). Non-participant observation of patient-clinician consultations (n=20-30) will be used to explore communication of treatment options and decision-making. Extent of participation in decision-making will be assessed using the Observing Patient Involvement in Shared Decision-Making tool. Interviews with patients (stage III) and their clinicians (stage IV) will explore the perception of treatment options and involvement in decision-making. Based on stages I-IV, an expert consensus meeting will finalise the content and format of the intervention. Cognitive interviews with patients will then determine the face validity of the intervention (stage V). Analysis : analysis will be according to data type and research question and will include mediated discourse analysis, thematic analysis, framework analysis and interpretative phenomenological analysis. Ethical approval has been granted. The study findings will contribute to and promote shared and informed decision-making in the best interest of patients and prudent healthcare. We therefore aim to disseminate results via relevant respiratory, oncology and palliative care journals and conferences. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. International Myeloma Working Group recommendations for global myeloma care.

    PubMed

    Ludwig, H; Miguel, J S; Dimopoulos, M A; Palumbo, A; Garcia Sanz, R; Powles, R; Lentzsch, S; Ming Chen, W; Hou, J; Jurczyszyn, A; Romeril, K; Hajek, R; Terpos, E; Shimizu, K; Joshua, D; Hungria, V; Rodriguez Morales, A; Ben-Yehuda, D; Sondergeld, P; Zamagni, E; Durie, B

    2014-05-01

    Recent developments have led to remarkable improvements in the assessment and treatment of patients with multiple myeloma (MM). New technologies have become available to precisely evaluate the biology and extent of the disease, including information about cytogenetics and genetic abnormalities, extramedullary manifestations and minimal residual disease. New, more effective drugs have been introduced into clinical practice, which enable clinicians to significantly improve the outcome of patients but also pose new challenges for the prevention and management of their specific side effects. Given these various new options and challenges, it is important to identify the minimal requirements for diagnosis and treatment of patients, as access to the most sophisticated advances may vary depending on local circumstances. Here, we propose the minimal requirements and possible options for diagnosis, monitoring and treatment of patients with multiple myeloma.

  11. Endobronchial cryotherapy facilitates end-stage treatment options in patients with bronchial stenosis: A case series

    PubMed Central

    Fitzmaurice, Gerard J.; Redmond, Karen C.; Fitzpatrick, David A.; Bartosik, Waldemar

    2014-01-01

    In keeping with international trends, lung cancer incidence and mortality are increasing among the Irish population with many patients presenting with advanced disease that excludes the potential for curative management. Consequently palliative treatment options for this patient group are being increasingly explored with various degrees of success. Endobronchial stenosis represents a particularly challenging area of management among these patients and a number of techniques have been described without the identification of a single gold standard. We report our experience of the first time use of endobronchial cryotherapy in Ireland with reference to a case series, including an example of its use in the management of benign disease, in order to support patients with borderline lung function and enable definitive palliative treatment. PMID:24791176

  12. Emerging Therapies for Scar Prevention

    PubMed Central

    Block, Lisa; Gosain, Ankush; King, Timothy W.

    2015-01-01

    Significance: There are ∼12 million traumatic lacerations treated in the United States emergency rooms each year, 250 million surgical incisions created worldwide every year, and 11 million burns severe enough to warrant medical treatment worldwide. In the United States, over $20 billion dollars per year are spent on the treatment and management of scars. Recent Advances: Investigations into the management of scar therapies over the last decade have advanced our understanding related to the care of cutaneous scars. Scar treatment methods are presented including topical, intralesional, and mechanical therapies in addition to cryotherapy, radiotherapy, and laser therapy. Critical Issues: Current treatment options for scars have significant limitations. This review presents the current and emerging therapies available for scar management and the scientific evidence for scar management is discussed. Future Directions: Based upon our new understanding of scar formation, innovative scar therapies are being developed. Additional research on the basic science of scar formation will lead to additional advances and novel therapies for the treatment of cutaneous scars. PMID:26487979

  13. Oncologic principles in breast reconstruction.

    PubMed

    Cho, B C John; McCready, David R

    2007-01-01

    Breast cancer is the most common malignancy in North American women. Although the incidence has risen over the last 20 years, mortality rates appear to be decreasing, possibly as a result of earlier detection and more effective therapy. Breast cancer is a heterogeneous group of conditions that can be divided into the noninvasive entities of lobular carcinoma in situ (LCIS) and ductal carcinoma-in-situ (DCIS), and invasive cancers. In this article, the spectrum of breast cancer is presented from the noninvasive entities, through invasive breast cancer types, to advanced and recurrent cancer. The rationales for current treatment options are presented. Evidence is presented for current adjuvant treatment options, and the rationale for surgical decision-making is presented.

  14. Increasing physical activity and exercise in lung cancer: reviewing safety, benefits, and application.

    PubMed

    Bade, Brett C; Thomas, D David; Scott, JoAnn B; Silvestri, Gerard A

    2015-06-01

    Lung cancer continues to be a difficult disease frequently diagnosed in late stages with a high mortality and symptom burden. In part because of frequent lung comorbidity, even lung cancer survivors often remain symptomatic and functionally limited. Though targeted therapy continues to increase treatment options for advanced-stage disease, symptom burden remains high with few therapeutic options. In the last several decades, exercise and physical activity have arisen as therapeutic options for obstructive lung disease and lung cancer. To date, exercise has been shown to reduce symptoms, increase exercise tolerance, improve quality of life, and potentially reduce length of stay and postoperative complications. Multiple small trials have been performed in perioperative non-small-cell lung cancer patients, although fewer studies are available for patients with advanced-stage disease. Despite the increased interest in this subject over the last few years, a validated exercise regimen has not been established for perioperative or advanced-stage disease. Clinicians underutilize exercise and pulmonary rehabilitation as a therapy, in part because of the lack of evidence-based consensus as to how and when to implement increasing physical activity. This review summarizes the existing evidence on exercise in lung cancer patients.

  15. Endocrine therapy for postmenopausal women with hormone receptor-positive her2-negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement.

    PubMed

    Pritchard, K I; Gelmon, K A; Rayson, D; Provencher, L; Webster, M; McLeod, D; Verma, S

    2013-02-01

    Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2-) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients-efect, sofea, confirm, and bolero-2-have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2- advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient's age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged.

  16. Endocrine therapy for postmenopausal women with hormone receptor–positive her2–negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement

    PubMed Central

    Pritchard, K.I.; Gelmon, K.A.; Rayson, D.; Provencher, L.; Webster, M.; McLeod, D.; Verma, S.

    2013-01-01

    Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2–) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients—efect, sofea, confirm, and bolero-2—have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2– advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient’s age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged. PMID:23443928

  17. A review of ropinirole prolonged release in Parkinson’s disease

    PubMed Central

    Nashatizadeh, Muhammad M; Lyons, Kelly E; Pahwa, Rajesh

    2009-01-01

    Ropinirole prolonged release is a once-daily, 24-hour formulation of ropinirole, a non-ergot dopamine agonist. It is approved as monotherapy and as an adjunct to levodopa in the treatment of Parkinson’s disease (PD). Several potential advantages of ropinirole prolonged release compared to the immediate release formulation include maintaining more consistent dopaminergic activity with steadier plasma levels, increased tolerability, greater compliance from a simpler once-daily dosing regimen and ease in dose titration. In a randomized, double-blind, non-inferiority, crossover study, ropinirole prolonged release was shown to have comparable efficacy and tolerability to immediate release ropinirole in early PD patients, with significantly greater compliance. Subjects were converted overnight between ropinirole formulations without loss of efficacy and with good tolerability. In a randomized, double-blind, placebo-controlled study in advanced PD, daily “off” time was reduced by an average of 2.1 hours with ropinirole prolonged release compared to 0.4 hours with placebo. Patients on ropinirole prolonged release were also more likely to require less daily levodopa. Ropinirole prolonged release is well tolerated with a similar adverse effect profile to other non-ergot dopamine agonists. The most common adverse effects include dyskinesia, nausea, dizziness, hallucinations, somnolence, abdominal pain or discomfort and orthostatic hypotension. Ropinirole prolonged release is a safe and effective treatment option for both early and advanced PD. This manuscript briefly reviews the current pharmacological treatment options for PD and provides a more detailed review of the currently available data regarding ropinirole prolonged release as a treatment option for PD. PMID:19503779

  18. The Oncofertility Consortium—addressing fertility in young people with cancer

    PubMed Central

    Woodruff, Teresa K.

    2011-01-01

    The number of young cancer survivors is increasing owing to advances in cancer therapeutics, but many face infertility as a result of their treatment. Technologies that already exist for cancer patients concerned about their future fertility include sperm banking for men and hormonal intervention followed by in vitro fertilization and embryo cryopreservation for women. However, logistical barriers to timely patient referral and coordination of care between specialties can limit patient access to all the available options. Moreover, there are few alternatives for young women and girls who cannot delay their cancer treatment, or who are unable to undergo hormonal intervention. The Oncofertility Consortium is a network of researchers, physicians and scholars who are advancing fertility preservation options for young cancer patients. Research into the societal, ethical, and legal implications is also an important part of the work performed by the Oncofertility Consortium, which is providing new perspectives on patient decision making about how to access these emerging reproductive technologies. Experts in the fields of oncology, reproductive medicine, the social sciences, law, education, and the humanities are working together to develop next generation reproductive interventions and promote communication between scholars, clinicians, patients, and the public to ensure that young cancer patients are equipped with the most appropriate information and options for having a family in the future. PMID:20498666

  19. Fertility effects of cancer treatment.

    PubMed

    Marsden, Donald E; Hacker, Neville

    2003-01-01

    Cancer sufferers are a subfertile group, and most treatments have the potential to adversely affect gonadal function. As cancer treatment becomes more effective and survival rates improve there are more cancer survivors in the reproductive age group for whom parenting is an important consideration. This article outlines the effects on fertility of cancer treatments and techniques to minimise the risk of infertility. The overall prospects for younger cancer sufferers to either retain their fertility or have genetic offspring is now better than ever before, due to advances in assisted reproductive technology, the appropriate use of fertility sparing surgery and other techniques to reduce the toxicity of therapy on the reproductive organs. These advances raise new moral and ethical concerns that must be considered before advising cancer sufferers of the options for preserving reproductive capacity.

  20. Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015

    PubMed Central

    Gillessen, S.; Omlin, A.; Attard, G.; de Bono, J. S.; Efstathiou, E.; Fizazi, K.; Halabi, S.; Nelson, P. S.; Sartor, O.; Smith, M. R.; Soule, H. R.; Akaza, H.; Beer, T. M.; Beltran, H.; Chinnaiyan, A. M.; Daugaard, G.; Davis, I. D.; De Santis, M.; Drake, C. G.; Eeles, R. A.; Fanti, S.; Gleave, M. E.; Heidenreich, A.; Hussain, M.; James, N. D.; Lecouvet, F. E.; Logothetis, C. J.; Mastris, K.; Nilsson, S.; Oh, W. K.; Olmos, D.; Padhani, A. R.; Parker, C.; Rubin, M. A.; Schalken, J. A.; Scher, H. I.; Sella, A.; Shore, N. D.; Small, E. J.; Sternberg, C. N.; Suzuki, H.; Sweeney, C. J.; Tannock, I. F.; Tombal, B.

    2015-01-01

    The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged. PMID:26041764

  1. Evidence-based practice: management of glottic cancer.

    PubMed

    Hartl, Dana M

    2012-10-01

    The main issue in the management of glottic squamous cell carcinoma, as for all cancers, is adequate disease control while optimizing functional outcomes and minimizing morbidity. This is true for early-stage disease as for advanced tumors. This article evaluates the current evidence for the diagnostic and pretherapeutic workup for glottic squamous cell carcinoma and the evidence concerning different treatment options for glottic carcinoma, from early-stage to advanced-stage disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Treatment challenges for community oncologists treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

    PubMed Central

    Gradishar, William J

    2016-01-01

    Community-based oncologists are faced with challenges and opportunities when delivering quality patient care, including high patient volumes and diminished resources; however, there may be the potential to deliver increased patient education and subsequently improve outcomes. This review discusses the treatment of postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2- negative advanced breast cancer in order to illustrate considerations in the provision of pertinent quality education in the treatment of these patients and the management of therapy-related adverse events. An overview of endocrine-resistant breast cancer and subsequent treatment challenges is also provided. Approved treatment options for endocrine-resistant breast cancer include hormonal therapies and mammalian target of rapamycin inhibitors. Compounds under clinical investigation are also discussed. PMID:27468248

  3. Therapeutic outcomes of mandibular advancement devices as an initial treatment modality for obstructive sleep apnea.

    PubMed

    Park, Pona; Jeon, Hyoung Won; Han, Doo Hee; Won, Tae-Bin; Kim, Dong-Young; Rhee, Chae-Seo; Kim, Hyun Jik

    2016-11-01

    Although continuous positive airway pressure (CPAP) is a highly efficacious treatment for obstructive sleep apnea (OSA), there is a need for alternative treatment options, such as sleep surgeries and mandibular advancement devices (MADs), to overcome the limitations of CPAP.This study aimed to analyze the therapeutic outcomes of OSA subjects who were treated with a MAD, and to estimate the clinical impact of MAD as a first-line treatment for OSA.Forty-seven patients diagnosed with OSA received an adjustable MAD as an initial treatment. Drug-induced sleep endoscopic findings and sleep parameters (both pre-MAD and post-MAD treatment), such as apnea index, oxygen saturation, and degree of daytime sleepiness, were assessed retrospectively.The MAD treatment resulted in a significant reduction in apnea-hypopnea index, and also a significant elevation in lowest oxygen saturation. Satisfactory results of MAD treatment as a first treatment modality were observed in 27 patients, and a successful outcome was reached in approximately 72% of patients. The OSA patients who had lower body mass index and upper airway narrowing at the level of palate and tongue base showed relatively higher rates of a satisfactory outcome even in cases of moderate or severe OSA.These results suggest that the use of a MAD may be an alternative treatment option in OSA patients with retropalatal and retroglossal area narrowing regardless of disease severity. Additionally, MADs can be recommended as an initial treatment modality, and the effectiveness of MADs in achieving success may not be inferior to CPAP.

  4. Therapeutic outcomes of mandibular advancement devices as an initial treatment modality for obstructive sleep apnea

    PubMed Central

    Park, Pona; Jeon, Hyoung Won; Han, Doo Hee; Won, Tae-Bin; Kim, Dong-Young; Rhee, Chae-Seo; Kim, Hyun Jik

    2016-01-01

    Abstract Although continuous positive airway pressure (CPAP) is a highly efficacious treatment for obstructive sleep apnea (OSA), there is a need for alternative treatment options, such as sleep surgeries and mandibular advancement devices (MADs), to overcome the limitations of CPAP. This study aimed to analyze the therapeutic outcomes of OSA subjects who were treated with a MAD, and to estimate the clinical impact of MAD as a first-line treatment for OSA. Forty-seven patients diagnosed with OSA received an adjustable MAD as an initial treatment. Drug-induced sleep endoscopic findings and sleep parameters (both pre-MAD and post-MAD treatment), such as apnea index, oxygen saturation, and degree of daytime sleepiness, were assessed retrospectively. The MAD treatment resulted in a significant reduction in apnea–hypopnea index, and also a significant elevation in lowest oxygen saturation. Satisfactory results of MAD treatment as a first treatment modality were observed in 27 patients, and a successful outcome was reached in approximately 72% of patients. The OSA patients who had lower body mass index and upper airway narrowing at the level of palate and tongue base showed relatively higher rates of a satisfactory outcome even in cases of moderate or severe OSA. These results suggest that the use of a MAD may be an alternative treatment option in OSA patients with retropalatal and retroglossal area narrowing regardless of disease severity. Additionally, MADs can be recommended as an initial treatment modality, and the effectiveness of MADs in achieving success may not be inferior to CPAP. PMID:27861349

  5. Immune Suppression Enhances Effectiveness of Mesothelioma Targeted Immunotoxin | Center for Cancer Research

    Cancer.gov

    Malignant mesothelioma is an aggressive cancer of the linings of the organs in the chest and the abdomen and is often caused by exposure to asbestos. Although patients with localized disease may be treated effectively with surgery, those with more-advanced mesothelioma have few approved treatment options.

  6. Treatment of severe lupus nephritis: the new horizon.

    PubMed

    Chan, Tak Mao

    2015-01-01

    Lupus nephritis is a common and severe manifestation of systemic lupus erythematosus, and an important cause of both acute kidney injury and end-stage renal disease. Despite its aggressive course, lupus nephritis is amenable to treatment in the majority of patients. The paradigm of immunosuppressive treatment for lupus nephritis has evolved over the past few decades from corticosteroids alone to corticosteroids combined with cyclophosphamide. Sequential treatment regimens using various agents have been formulated for induction and long-term maintenance therapy, and mycophenolate mofetil has emerged as a standard of care option for both induction and maintenance immunosuppressive treatment. The current era has witnessed the emergence of multiple novel therapeutic options, such as calcineurin inhibitors and biologic agents that target key pathogenetic mechanisms of lupus nephritis. Clinical outcomes have improved in parallel with these therapeutic advances. This Review discusses the evidence in support of current standard of care immunosuppressive treatments and emerging therapies, and describes their roles and relative merits in the management of patients with lupus nephritis.

  7. Emerging biological therapies for the treatment of myelodysplastic syndromes.

    PubMed

    Zeidan, Amer M; Stahl, Maximilian; Komrokji, Rami

    2016-09-01

    No drug has resulted in a survival advantage in patients with lower-risk myelodysplastic syndromes (MDS). While hypomethylating agents (HMA) have revolutionized treatment options for patients with higher-risk MDS, the prognosis remains dismal after HMA treatment failure. Novel effective therapies are urgently needed especially after HMA failure. This review covers the current approach to disease prognostication and risk-adaptive therapy, as well as novel therapeutic approaches. We discuss the recent advancements in the understanding of MDS disease biology as a basis of targeted drug development. Several classes of novel agents are reviewed including drugs targeting dysregulated epigenetic control mechanisms, signaling pathways, abnormal splicing, as well as agents that target the immune system and the MDS bone marrow niche. Significant advancements in the understanding of the underlying biology of MDS are only starting to be translated into novel treatment options for MDS. Epigenetic therapy has shown significant clinical activity with HMA but the results of clinical trials combining HMAs with histone deacetylase inhibitors (HDACi) have been disappointing to date. Similarly, targeting several aberrant pathways in MDS has not resulted in significant improvements in therapy. Future therapies will focus both on synergic combination of existing drugs as well as novel agents targeting dysregulated immune responses and abnormal RNA splicing in MDS.

  8. New pharmacotherapy for the treatment of glaucoma.

    PubMed

    Schehlein, Emily M; Novack, Gary; Robin, Alan L

    2017-12-01

    Glaucoma is the second leading cause of blindness in the world and current pharmacotherapies for glaucoma have remained relatively unchanged (with the exception of fixed combinations of previously available medications) since the mid-1990s with the development of prostaglandin analogues. Now, with both new formulations and new classes of medications with novel mechanisms of action, the medical therapy of glaucoma may be heralding a new dawn in medical management. Areas covered: This review outlines new topical therapies for intraocular pressure (IOP) lowering treatment, in addition to new formulations, preservative-free options, and advances in glaucoma medical therapy delivery. We performed a comprehensive search for published studies for glaucoma medical therapy using the electronic database PubMed. A manual search for each therapy or delivery system was also performed. Expert commentary: These advances in glaucoma therapy have the potential to overcome many barriers to glaucoma's medical care, particularly in terms of adherence. However, both time and research are needed to prove the relative efficacy and safety of these new pharmacotherapies and products, helping us decide their role in the treatment of elevated intraocular pressure. We are hopeful that these new developments in therapy may bring more options for glaucoma medical therapy.

  9. Ebola virus convalescent blood products: where we are now and where we may need to go.

    PubMed

    Burnouf, Thierry; Seghatchian, Jerard

    2014-10-01

    The world is regularly exposed to emerging infections with the potential to burst into a pandemic. One possible way to treat patients, when no other treatment is yet developed,is passive immunization performed by transfusing blood, plasma or plasma immunoglobul infractions obtained from convalescent donors who have recovered from the disease and have developed protective antibodies. The most recent on-going epidemic is caused by the Ebola virus, a filovirus responsible for Ebola virus disease, a severe, often lethal, hemorrhagic fever. Recently, the use of convalescent blood products was proposed by the WHO as one early option for treating patients with Ebola virus disease. This publication provides an overview of the various convalescent blood products and technological options that could theoretically be considered when there is a need to rely on this therapeutic approach.In countries without access to advanced blood-processing technologies, the choice may initially be restricted to convalescent whole blood or plasma. In technologically advanced countries, additional options for convalescent blood products are available, including virally inactivated plasma and fractionated immunoglobulins. The preparation of minipool immunoglobulins is also a realistic option to consider.

  10. Coronally advanced flap with and without a xenogenic collagen matrix in the treatment of multiple recessions: a randomized controlled clinical study.

    PubMed

    Cardaropoli, Daniele; Tamagnone, Lorenzo; Roffredo, Alessandro; Gaveglio, Lorena

    2014-01-01

    Multiple adjacent recession defects were treated in 32 patients using a coronally advanced flap (CAF) with or without a collagen matrix (CM). The percentage of root coverage was 81.49% ± 23.45% (58% complete root coverage) for CAF sites (control) and 93.25% ± 10.01% root coverage (72% complete root coverage) for CM plus CAF sites (test). The results achieved in the test group were significantly greater than in the control group, indicating that CM plus CAF is a suitable option for the treatment of multiple adjacent gingival recessions.

  11. Rehabilitation Options

    MedlinePlus

    ... Speech Pathology Occupational Therapy Art Therapy Recreational therapy Neuropsychology Home Care Options Advanced Care Planning Palliative Care ... Speech Pathology Occupational Therapy Art Therapy Recreational therapy Neuropsychology Home Care Options Advanced Care Planning Palliative Care ...

  12. Alternatives in the complement and structure of NASA teleprocessing resources

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The results are presented of a program to identify technical innovations which would have an impact on NASA data processing and describe as fully as possible the development work necessary to exploit them. Seven of these options for NASA development, as the opportunities to participate in and enhance the advancing information system technology were called, are reported. A detailed treatment is given of three of the options, involving minicomputers, mass storage devices and software development techniques. These areas were picked by NASA as having the most potential for improving their operations.

  13. New insights into the diagnosis and treatment of dry eye.

    PubMed

    Dogru, Murat; Tsubota, Kazuo

    2004-04-01

    Over the past decade, numerous advances have been made in relation to dry eye diagnostic markers, technologies, and treatment options. The mainstay of treatment of dry eye is the use of artificial tear solutions and punctum plugs. A goal is the development of agents that provide symptomatic treatment and, at the same time, improve ocular surface keratinization. It is the authors' opinion that the functional visual acuity tester and the new tear stability analysis system will be widely used to improve diagnosis and evaluate treatment outcomes in KCS. Advances in treatment will utilize anti-inflammatory agents, immune suppressants such as Cyclosporin A and FK-506, growth hormones, androgens, topical mucins and ocular surface stimulating drugs, like INS365. Although aqueous-deficient dry eye is most commonly not associated with Sjogren syndrome (SS), aqueous-deficient dry eye is often most severe in patients with SS; thus, this article focuses mainly on SS-associated dry eye.

  14. Project HELP: a study protocol to pilot test a shared decision-making tool about treatment options for patients with hepatitis C and chronic kidney disease.

    PubMed

    Politi, M C; George, N; Li, T; Korenblat, K M; Fowler, K J; Ho, C; Liapakis, A; Roth, D; Yee, J

    2018-01-01

    Recent advances in treatment have given patients with chronic kidney disease (CKD) access to safer and more effective medications to treat comorbid hepatitis C virus (HCV) infection. Given the variety and complexity of treatment options that depend on patients' clinical characteristics and personal preferences, education and decision support are needed to prepare patients better to discuss treatment options with their clinicians. Drawing on International Patient Decision Aids Standards guidelines, literature reviews, and guidance from a diverse expert advisory group of nephrologists, hepatologists, and patients, we will develop and test a HCV and CKD decision support tool. Named Project HELP ( Helping Empower Liver and kidney Patients ), this tool will support patients with HCV and CKD during decisions about whether, when, and how to treat each illness. The tool will (1) explain information using plain language and graphics; (2) provide a step-by-step process for thinking about treating HCV and CKD; (3) tailor relevant information to each user by asking about the individual's stage of CKD, stage of fibrosis, prior treatment, and comorbidities; (4) assess user knowledge and values for treatment choices; and (5) help individuals use and consider information appropriate to their values and needs to discuss with a clinician. A pilot study including 70 individuals will evaluate the tool's efficacy, usability, and likelihood of using it in clinical practice. Eligibility criteria will include individuals who understand and read English, who are at least 18 years old, have a diagnosis of HCV (any genotype) and CKD (any stage), and are considering treatment options. This study can identify particular characteristics of individuals or groups that might experience challenges initiating treatment for HCV in the CKD population. This tool could provide a resource to facilitate patient-clinician discussions regarding HCV and CKD treatment options.

  15. Hematopoietic stem cell transplantation for myelofibrosis: where are we now?

    PubMed

    Fleischman, Angela G; Maziarz, Richard T

    2013-03-01

    A succinct yet comprehensive review of the biology of myeloproliferative neoplasms and therapeutic options with a focus on rational decision making for hematopoietic stem cell transplantation. The introduction of Janus kinase inhibitors for myelofibrosis have ushered in a new era for treatment of constitutional symptoms and splenomegaly in myelofibrosis, but the effect of these agents on the natural history of the disease has yet to be clearly defined. Reduced intensity transplants have emerged as the preferred option with recent evidence suggesting fludarabine and melphalan as the optimal conditioning regimen. Myelofibrosis is a rare hematologic malignancy with limited curative therapeutic options. Significant advances in our understanding of disease pathogenesis have led to new targets and new therapeutic options are forthcoming. Hematopoietic stem cell transplantation is at present the only treatment with curative intent; however, the selection of patients who are likely to be best served by this procedure is difficult. As myelofibrosis is an extremely rare disease, randomized clinical trials specifically investigating the role of transplantation in myelofibrosis are unlikely to occur, thus current decision making processes are best guided by retrospective analyses from registry databases and single institution experiences.

  16. Apatinib treatment combined with chemotherapy for advanced epithelial ovarian cancer: a case report.

    PubMed

    Deng, Linghui; Wang, Yue; Lu, Wenbin; Liu, Qian; Wu, Jie; Jin, Jianhua

    2017-01-01

    Apatinib is a novel oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has been proved by clinical trials to be effective and safe for patients with chemotherapy-refractory gastric cancer. To date, there is no study or case report on apatinib treatment for patients with ovarian cancer. Here, we present the case of a 50-year-old Chinese woman with advanced ovarian cancer, who received apatinib at a daily dose of 500 mg for 28 days per cycle after failure of fourth-line chemotherapy. Favorable oncologic outcome was achieved in this case after treatment with apatinib. The patient's progression-free survival is now 11.3 months, and she is taking apatinib and capecitabine as maintenance treatment. The common side effect of apatinib was fatigue; however, the toxicity of apatinib was controllable and tolerable. Thus, apatinib may be an option for chemotherapy-refractory advanced epithelial ovarian cancer, but this still warrants further investigation.

  17. Primary mucosal sinonasal melanoma—Case report and review of the literature. The role of complex treatment-surgery and adjuvant radiotherapy

    PubMed Central

    Marinova, Lena; Yordanov, Kaloyan; Sapundgiev, Nikolay

    2010-01-01

    Aim The place of adjuvant radiotherapy in the treatment of sinonasal melanoma. Background Sinonasal mucosal melanoma is a rare disease with poor prognosis and requires a complex treatment. Elective neck dissection in patients with N0 and adjuvant radiotherapy has been a source of controversy. High late regional recurrence rates rise questions about elective irradiation of the neck nodes in patients with N0 stage disease. Methods We present our two years’ follow up in a case of locally advanced sinonasal melanoma and literature review of the treatment options for mucosal melanoma. Results In locally advanced sinonasal melanoma treated with surgical resection, postoperative radiotherapy and chemotherapy we had local tumor control. Two years later, a regional contralateral recurrence without distant metastasis occurred. Conclusions Literature data for frequent neck lymph nodes recurrences justify elective neck dissection. Postoperative elective neck radiotherapy for patients with locally advanced sinonasal melanoma and clinically N0 appears to decrease the rate of late regional recurrences. PMID:24376954

  18. Recent advances in treatment of aplastic anemia

    PubMed Central

    Shin, Seung Hwan; Lee, Sung Eun

    2014-01-01

    Recent advances in the treatment of aplastic anemia (AA) made most of patients to expect to achieve a long-term survival. Allogeneic stem cell transplantation (SCT) from HLA-matched sibling donor (MSD-SCT) is a preferred first-line treatment option for younger patients with severe or very severe AA, whereas immunosuppressive treatment (IST) is an alternative option for others. Horse anti-thymocyte globuline (ATG) with cyclosporin A (CsA) had been a standard IST regimen with acceptable response rate. Recently, horse ATG had been not available and replaced with rabbit ATG in most countries. Subsequently, recent comparative studies showed that the outcomes of patients who received rabbit ATG/CsA were similar or inferior compared to those who received horse ATG/CsA. Therefore, further studies to improve the outcomes of IST, including additional eltrombopag, are necessary. On the other hand, the upper age limit of patients who are able to receive MSD-SCT as first-line treatment is a current issue because of favorable outcomes of MSD-SCT of older patients using fludarabine-based conditioning. In addition, further studies to improve the outcomes of patients who receive allogeneic SCT from alternative donors are needed. In this review, current issues and the newly emerging trends that may improve their outcomes in near futures will be discussed focusing the management of patients with AA. PMID:25378968

  19. [Treatment of posterior noninfectious uveitis : Current situation and future developments].

    PubMed

    Pleyer, U; Pohlmann, D; Stübiger, N

    2016-05-01

    Treatment of autoimmune diseases has undergone significant changes and developments in recent years. New classes of active substances, in particular biologics and small molecules have resulted in previously unknown success in the treatment of many diseases. In particular patients suffering from autoimmune rheumatic or dermatological diseases have benefited. For autoimmune uveitis there are numerous reports indicating excellent therapeutic and preventive effects; however, statutory approval for therapy in adults is still pending. This article outlines recent advances and future therapeutic options for the treatment of posterior segment noninfectious uveitis.

  20. Comprehensive Approaches to Managing Delirium in Patients with Advanced Cancer

    PubMed Central

    Kang, Jung Hun; Shin, Seong Hoon; Bruera, Eduardo

    2013-01-01

    Delirium is a frequently under-recognized complication in patients with advanced cancer. Uncontrolled delirium eventually leads to significant distress to patients and their families. However, delirium episodes can be reversed in half of these patients by eliminating precipitating factors and using appropriate interventions. The purpose of this narrative review is to discuss the most recent updates in the literature on the management of delirium in patients with advanced cancer. This article addresses the epidemiology, cause, pathophysiology, clinical characteristics, and assessment of delirium as well as various treatment options, including nonpharmacologic intervention and palliative sedation. PMID:22959227

  1. Inapplicability of advance directives in a paternalistic setting: the case of a post-communist health system

    PubMed Central

    2011-01-01

    Background The Albanian medical system and Albanian health legislation have adopted a paternalistic position with regard to individual decision making. This reflects the practices of a not-so-remote past when state-run facilities and a totalitarian philosophy of medical care were politically imposed. Because of this history, advance directives concerning treatment refusal and do-not-resuscitate decisions are still extremely uncommon in Albania. Medical teams cannot abstain from intervening even when the patient explicitly and repeatedly solicits therapeutic abstinence. The Albanian law on health care has no provisions regarding limits or withdrawal of treatment. This restricts the individual's healthcare choices. Discussion The question of 'medically futile' interventions and pointless life-prolonging treatment has been discussed by several authors. Dutch physicians call such interventions 'medisch zinloos' (senseless), and the Netherlands, as one of the first states to legislate on end-of-life situations, actually regulates such issues through appropriate laws. In contrast, leaving an 'advance directive' is not a viable option for Albanian ailing individuals of advanced age. Verbal requests are provided during periods of mental competence, but unfortunately such instructions are rarely taken seriously, and none of them has ever been upheld in a legal or other official forum. Summary End-of-life decisions, treatment refusal and do-not-resuscitate policies are hazardous options in Albania, from the legal point of view. Complying with them involves significant risk on the part of the physician. Culturally, the application of such instructions is influenced from a mixture of religious beliefs, death coping-behaviors and an immense confusion concerning the role of proxies as decision-makers. Nevertheless, Albanian tradition is familiar with the notion of 'amanet', a sort of living will that mainly deals the property and inheritance issues. Such living wills, verbally transmitted, may in certain cases include advance directives regarding end-of-life decisions of the patient including refusal or termination of futile medical treatments. Since these living wills are never formally and legally validated, their application is impossible and treatment refusal remains still non practicable. Tricks to avoid institutional treatment under desperate conditions are used, aiming to provide legal coverage for medical teams and relatives that in extreme situations comply with the advice of withholding senseless treatment. PMID:21676261

  2. New treatment options for lower respiratory tract infections.

    PubMed

    Kocsis, Bela; Szabo, Dora

    2017-09-01

    Community-acquired pneumonia (CAP) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are among the most frequent lower respiratory tract infections (LRTIs). They represent an increased morbidity and mortality rate in adults. Areas covered: This review describes recent advances regarding solithromycin, zabofloxacin and delafoxacin antibacterial agents that have been recently developed for treatment of CAP and in AECOPD. All of them have been introduced into phase III clinical trials. We will be summarising chemical structures, pharmacokinetics, antibacterial efficacy and toxicity of these agents. The manuscript has been prepared based on available scientific publications. Expert opinion: Novel agents of known antimicrobial classes have been developed that demonstrate treatment options in CAP and in AECOPD. Antimicrobials discussed in this review showed bactericide effect against major respiratory tract pathogens. Each has multiple targets in bacteria, thus enabling them for more potency, even against strains exhibiting resistance to commonly used antibiotics. Solithromycin, delafloxacin and zabofloxcian demonstrate broad-spectrum antibacterial activity together with other beneficial features like intracellular accumulation, anti-inflammatory effect and inhibition of biofilm production. These agents showed moderately severe or mild adverse events and demonstrated favourable tissue penetration. These features can make solithromycin, zabofloxacin and delafloxacin treatment options in LRTIs.

  3. Treatment of hepatocellular carcinoma with portal vein tumor thrombus: advances and challenges.

    PubMed

    Jiang, Jin-Fang; Lao, Yong-Cong; Yuan, Bao-Hong; Yin, Jun; Liu, Xin; Chen, Long; Zhong, Jian-Hong

    2017-05-16

    Portal vein tumor thrombus is a frequent, challenging complication in hepatocellular carcinoma. Hepatocellular carcinoma patients with portal vein tumor thrombus may show worse liver function, less treatment tolerance and worse prognosis than patients without portal vein tumor thrombus, and they may be at higher risk of comorbidity related to portal hypertension. Western and some Asian guidelines stratify hepatocellular carcinoma with portal vein tumor thrombus together with metastatic hepatocellular carcinoma and therefore recommend only palliative treatment with sorafenib or other systemic agents. In recent years, more treatment options have become available for hepatocellular carcinoma patients with portal vein tumor thrombus, and an evidence-based approach to optimizing disease management and treatment has become more widespread. Nevertheless, consensus policies for managing hepatocellular carcinoma with portal vein tumor thrombus have not been established. This comprehensive literature review, drawing primarily on studies published after 2010, examines currently available management options for patients with hepatocellular carcinoma and portal vein tumor thrombus.

  4. Surgical management of corneal infections.

    PubMed

    Tuli, Sonal; Gray, Matthew

    2016-07-01

    The purpose of this review is to discuss the options for, and recent developments in, the surgical treatment of corneal infections. Although the mainstay of treatment of corneal infections is topical antimicrobial agents, surgical intervention may be necessary in a number of cases. These include advanced disease at presentation, resistant infections, and progressive ulceration despite appropriate treatment. Prompt and appropriate treatment can make the difference between a good outcome and loss of vision or the eye. There are a number of surgical therapies available for corneal infections. Preferred therapeutic modalities differ based on the size, causation, and location of the infection but consist of either replacement of the infected tissue or structural support of the tissue to allow healing. Although there are no completely novel therapies that have been developed recently, there have been incremental improvements in the existing treatment modalities making them more effective, easier, and safer. Several options are available for surgically managing corneal infections. Ophthalmologists should select the optimal procedure based on the individual patient's situation. http://links.lww.com/COOP/A20.

  5. Surgical management of corneal infections

    PubMed Central

    Tuli, Sonal; Gray, Matthew

    2016-01-01

    Purpose of review The purpose of this review is to discuss the options for, and recent developments in, the surgical treatment of corneal infections. While the mainstay of treatment of corneal infections is topical antimicrobial agents, surgical intervention may be necessary in a number of cases. These include advanced disease at presentation, resistant infections, and progressive ulceration despite appropriate treatment. Prompt and appropriate treatment can make the difference between a good outcome and loss of vision or the eye. Recent findings There are a number of surgical therapies available for corneal infections. Preferred therapeutic modalities differ based on the size, causation, and location of the infection but consist of either replacement of the infected tissue or structural support of the tissue to allow healing. While there are no completely novel therapies that have been developed recently, there have been incremental improvements in the existing treatment modalities making them more effective, easier, and safer. Summary Several options are available for surgically managing corneal infections. Ophthalmologists should select the optimal procedure based on the individual patient’s situation. PMID:27096375

  6. Recent Advances and Developments in Knee Surgery: Principles of Periprosthetic Knee Fracture Management

    PubMed Central

    Chimutengwende-Gordon, Mukai; Khan, Wasim; Johnstone, David

    2012-01-01

    The management of distal femoral, tibial and patellar fractures after total knee arthroplasty can be complex. The incidence of these fractures is increasing as the number of total knee arthroplasties being performed and patient longevity is increasing. There is a wide range of treatment options including revision arthroplasty for loose implants. This review article discusses the epidemiology, risk factors, classification and treatment of these fractures. PMID:22888380

  7. Telangiectatic osteosarcoma: a review of literature.

    PubMed

    Liu, Jun-Jian; Liu, Shen; Wang, Jian-Guang; Zhu, Wei; Hua, Ying-Qi; Sun, Wei; Cai, Zheng-Dong

    2013-01-01

    Telangiectatic osteosarcoma is a rare variant of osteosarcoma and hence its occurrence, presentation, and prognosis are poorly understood. With advancements in technology and available treatment options, the scenario of its diagnosis, management, and outcome has changed. Chemotherapy with surgery was challenged previously, but has now been proved to be beneficial. We reviewed the available literature and compared results to define the characteristics of the disease, its presentation, radiographic and pathologic features, optimal treatment, and prognosis.

  8. Telangiectatic osteosarcoma: a review of literature

    PubMed Central

    Liu, Jun-jian; Liu, Shen; Wang, Jian-guang; Zhu, Wei; Hua, Ying-qi; Sun, Wei; Cai, Zheng-dong

    2013-01-01

    Telangiectatic osteosarcoma is a rare variant of osteosarcoma and hence its occurrence, presentation, and prognosis are poorly understood. With advancements in technology and available treatment options, the scenario of its diagnosis, management, and outcome has changed. Chemotherapy with surgery was challenged previously, but has now been proved to be beneficial. We reviewed the available literature and compared results to define the characteristics of the disease, its presentation, radiographic and pathologic features, optimal treatment, and prognosis. PMID:23745051

  9. Myelodysplastic syndromes in older adults.

    PubMed

    Lindsey, Melissa; Beavers, Jill

    2010-10-01

    Myelodsyplastic syndromes are a collection of disorders that affect the hematopoietic development of myeloid cells in the bone marrow. Although this disorder is curable by way of allogeneic stem cell transplantation, advanced age, limited donor availability, and multiple comorbidities often exclude patients from curative treatment. Developments using the drugs lenalidomide, decitabine, and azacitidine have offered treatment options to patients ineligible for transplantation. Nurses remain instrumental in the administration, patient monitoring, and patient education associated with these new therapies.

  10. CMC Arthroplasty of the Thumb: A Review

    PubMed Central

    Ilyas, Asif; Thoder, Joseph J.

    2007-01-01

    Arthritis of the first carpometacarpal (CMC) joint of the hand is a common and often debilitating disease. Diagnosis can be readily made with history, physical exam, and radiographic evaluation. Patients with advanced disease who have failed conservative treatment modalities have multiple surgical options including ligament reconstruction, resection arthroplasty, silicone implantation, tendon interposition, or total joint arthroplasty. This article will describe the variety of approaches to treatment as well as the author’s preferred method. PMID:18780059

  11. Recent advances in the management of rectal cancer: No surgery, minimal surgery or minimally invasive surgery

    PubMed Central

    Plummer, Joseph M; Leake, Pierre-Anthony; Albert, Matthew R

    2017-01-01

    Over the last decade, with the acceptance of the need for improvements in the outcome of patients affected with rectal cancer, there has been a significant increase in the literature regarding treatment options available to patients affected by this disease. That treatment related decisions should be made at a high volume multidisciplinary tumor board, after pre-operative rectal magnetic resonance imaging and the importance of total mesorectal excision (TME) are accepted standard of care. More controversial is the emerging role for watchful waiting rather than radical surgery in complete pathologic responders, which may be appropriate in 20% of patients. Patients with early T1 rectal cancers and favorable pathologic features can be cured with local excision only, with transanal minimal invasive surgery (TAMIS) because of its versatility and almost universal availability of the necessary equipment and skillset in the average laparoscopic surgeon, emerging as the leading option. Recent trials have raised concerns about the oncologic outcomes of the standard “top-down” TME hence transanal TME (TaTME “bottom-up”) approach has gained popularity as an alternative. The challenges are many, with a dearth of evidence of the oncologic superiority in the long-term for any given option. However, this review highlights recent advances in the role of chemoradiation only for complete pathologic responders, TAMIS for highly selected early rectal cancer patients and TaTME as options to improve cure rates whilst maintaining quality of life in these patients, while we await the results of further definitive trials being currently conducted. PMID:28690773

  12. Advances in Radiotherapy for Glioblastoma

    PubMed Central

    Mann, Justin; Ramakrishna, Rohan; Magge, Rajiv; Wernicke, A. Gabriella

    2018-01-01

    External beam radiotherapy (RT) has long played a crucial role in the treatment of glioblastoma. Over the past several decades, significant advances in RT treatment and image-guidance technology have led to enormous improvements in the ability to optimize definitive and salvage treatments. This review highlights several of the latest developments and controversies related to RT, including the treatment of elderly patients, who continue to be a fragile and vulnerable population; potential salvage options for recurrent disease including reirradiation with chemotherapy; the latest imaging techniques allowing for more accurate and precise delineation of treatment volumes to maximize the therapeutic ratio of conformal RT; the ongoing preclinical and clinical data regarding the combination of immunotherapy with RT; and the increasing evidence of cancer stem-cell niches in the subventricular zone which may provide a potential target for local therapies. Finally, continued development on many fronts have allowed for modestly improved outcomes while at the same time limiting toxicity. PMID:29379468

  13. Advances in Radiotherapy for Glioblastoma.

    PubMed

    Mann, Justin; Ramakrishna, Rohan; Magge, Rajiv; Wernicke, A Gabriella

    2017-01-01

    External beam radiotherapy (RT) has long played a crucial role in the treatment of glioblastoma. Over the past several decades, significant advances in RT treatment and image-guidance technology have led to enormous improvements in the ability to optimize definitive and salvage treatments. This review highlights several of the latest developments and controversies related to RT, including the treatment of elderly patients, who continue to be a fragile and vulnerable population; potential salvage options for recurrent disease including reirradiation with chemotherapy; the latest imaging techniques allowing for more accurate and precise delineation of treatment volumes to maximize the therapeutic ratio of conformal RT; the ongoing preclinical and clinical data regarding the combination of immunotherapy with RT; and the increasing evidence of cancer stem-cell niches in the subventricular zone which may provide a potential target for local therapies. Finally, continued development on many fronts have allowed for modestly improved outcomes while at the same time limiting toxicity.

  14. Youth Risk Assessment in Complex Agency Practice

    ERIC Educational Resources Information Center

    Groner, Mark R.; Solomon, Jean

    2007-01-01

    Advancements in the delivery of community-based services and tight utilization management of high-cost treatment options result in youths with serious behavior problems receiving intervention in lower levels of care than was true ten or fifteen years ago. This shift in where services tend to be delivered necessitates enhancement of risk assessment…

  15. The Experiences of School Nurses Caring for Students Receiving Continuous Subcutaneous Insulin Infusion Therapy

    ERIC Educational Resources Information Center

    Darby, Wendy

    2006-01-01

    Diabetes mellitus is the most common metabolic disorder in childhood. Today, children with diabetes are receiving new technologically advanced treatment options, such as continuous subcutaneous insulin infusion (CSII) therapy. School nurses are the primary health caregivers of children with diabetes during school hours. Therefore, it is important…

  16. From bench to bedside: What do we know about hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer?

    PubMed

    Wu, Victoria Shang; Kanaya, Noriko; Lo, Chiao; Mortimer, Joanne; Chen, Shiuan

    2015-09-01

    Breast cancer is a heterogeneous disease. Thanks to extensive efforts from research scientists and clinicians, treatment for breast cancer has advanced into the era of targeted medicine. With the use of several well-established biomarkers, such as hormone receptors (HRs) (i.e., estrogen receptor [ER] and progesterone receptor [PgR]) and human epidermal growth factor receptor-2 (HER2), breast cancer patients can be categorized into multiple subgroups with specific targeted treatment strategies. Although therapeutic strategies for HR-positive (HR+) HER2-negative (HER2-) breast cancer and HR-negative (HR-) HER2-positive (HER2+) breast cancer are well-defined, HR+ HER2+ breast cancer is still an overlooked subgroup without tailored therapeutic options. In this review, we have summarized the molecular characteristics, etiology, preclinical tools and therapeutic options for HR+ HER2+ breast cancer. We hope to raise the attention of both the research and the medical community on HR+ HER2+ breast cancer, and to advance patient care for this subtype of disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Overview of Genetically Engineered Mouse Models of Distinct Breast Cancer Subtypes.

    PubMed

    Usary, Jerry; Darr, David Brian; Pfefferle, Adam D; Perou, Charles M

    2016-03-18

    Advances in the screening of new therapeutic options have significantly reduced the breast cancer death rate over the last decade. Despite these advances, breast cancer remains the second leading cause of cancer death among women. This is due in part to the complexity of the disease, which is characterized by multiple subtypes that are driven by different genetic mechanisms and that likely arise from different cell types of origin. Because these differences often drive treatment options and outcomes, it is important to select relevant preclinical model systems to study new therapeutic interventions and tumor biology. Described in this unit are the characteristics and applications of validated genetically engineered mouse models (GEMMs) of basal-like, luminal, and claudin-low human subtypes of breast cancer. These different subtypes have different clinical outcomes and require different treatment strategies. These GEMMs can be considered faithful surrogates of their human disease counterparts. They represent alternative preclinical tumor models to cell line and patient-derived xenografts for preclinical drug discovery and tumor biology studies. Copyright © 2016 John Wiley & Sons, Inc.

  18. Clinical roundtable monograph: new and emerging treatments for advanced prostate cancer.

    PubMed

    George, Daniel J; Kantoff, Philip W; Lin, Daniel W

    2011-06-01

    Historically, the treatment of metastatic castration-resistant prostate cancer (CRPC) has been limited to chemotherapeutic regimens that did not improve patient survival. In 2004, clinical studies began to demonstrate significant improvements in patient outcomes, including overall survival, with docetaxel versus mitoxantrone chemotherapy. Since these pivotal trials, the combination of docetaxel plus prednisone has become a standard of care for patients with metastatic CRPC. However, the limited survival benefit achieved with this regimen prompted several investigations into the development of alternative therapeutic options. Recent advances have now led to an unprecedented number of new drug approvals within the past year, providing many new treatment options for patients with metastatic CRPC. Sipuleucel-T, considered a new paradigm in cancer treatment, is the first such immunotherapeutic agent approved by the US Food and Drug Administration. Other successes include abiraterone acetate, the first androgen biosynthesis inhibitor, and cabazitaxel, a novel microtubule inhibitor, both of which have demonstrated improved survival following docetaxel failure. The bone-targeting agent denosumab, also recently approved in this setting, offers these patients significant improvement in the prevention of skeletal-related events. The data supporting the approval of each of these agents are described in this monograph, as are current approaches in the treatment of metastatic CRPC and ongoing clinical trials of novel treatments and strategies. The experts also discuss several of the issues regarding the introduction of these novel agents into clinical practice for metastatic CRPC patients.

  19. Advances in cryoablation for pancreatic cancer.

    PubMed

    Luo, Xiao-Mei; Niu, Li-Zhi; Chen, Ji-Bing; Xu, Ke-Cheng

    2016-01-14

    Pancreatic carcinoma is a common cancer of the digestive system with a poor prognosis. It is characterized by insidious onset, rapid progression, a high degree of malignancy and early metastasis. At present, radical surgery is considered the only curative option for treatment, however, the majority of patients with pancreatic cancer are diagnosed too late to undergo surgery. The sensitivity of pancreatic cancer to chemotherapy or radiotherapy is also poor. As a result, there is no standard treatment for patients with advanced pancreatic cancer. Cryoablation is generally considered to be an effective palliative treatment for pancreatic cancer. It has the advantages of minimal invasion and improved targeting, and is potentially safe with less pain to the patients. It is especially suitable in patients with unresectable pancreatic cancer. However, our initial findings suggest that cryotherapy combined with 125-iodine seed implantation, immunotherapy or various other treatments for advanced pancreatic cancer can improve survival in patients with unresectable or metastatic pancreatic cancer. Although these findings require further in-depth study, the initial results are encouraging. This paper reviews the safety and efficacy of cryoablation, including combined approaches, in the treatment of pancreatic cancer.

  20. 77 FR 62308 - Self-Regulatory Organizations; The Options Clearing Corporation; Notice of Filing of Advance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-12

    ... Organizations; The Options Clearing Corporation; Notice of Filing of Advance Notice and Notice of No Objection To Replace The Options Clearing Corporation's Credit Facility October 5, 2012. Pursuant to Section 19...\\ notice is hereby given that on September 26, 2012, The Options Clearing Corporation (``OCC'') filed with...

  1. 7 CFR 1781.14 - Planning, options, and appraisals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Planning, options, and appraisals. 1781.14 Section...) LOANS AND ADVANCES § 1781.14 Planning, options, and appraisals. (a) WS and RCD area plans are developed... designated agent when a WS loan, WS advance or RCD loan is made. (d) Options and appraisals related to the...

  2. Immunotherapy of patients with metastatic melanoma.

    PubMed

    Yu, Zhe; Si, Lu

    2017-04-01

    Malignant melanoma (MM) is the primary cause of skin cancer related death and the incidence is increasing in the past years. Advanced MM still has a poor prognosis, but in recent years, the development of immunotherapy has changed its poor prognosis. Immune checkpoints show the revolutionary treatment of metastatic melanoma. Ipilimumab and pembrolizumab, monoclonal antibodies against the CTLA-4 and PD-1 respectively, have been shown to prolong overall survival (OS) in patients with advanced melanoma. The combination immunotherapy seems to be superior to monotherapy. In this review, recently immunotherapy clinical trial results are presented. The combination of immunotherapy provides new options for the treatment of MM patients. However, further studies are necessary to answer such question as optimal treatment, combination of immunotherapies, crowd selection and risk balance in patients with melanoma.

  3. A review of drugs in development for the personalized treatment of head and neck squamous cell carcinoma

    PubMed Central

    Birkeland, Andrew C.; Swiecicki, Paul L.; Brenner, J. Chad; Shuman, Andrew G.

    2017-01-01

    Introduction Head and neck squamous cell carcinoma remains a highly morbid and fatal disease, with poor survival rates among patients with advanced and recurrent disease. Recent advances in next generation sequencing, targeted therapeutics, and precision medicine trials are expanding treatment options for head and neck cancers; thus greater awareness of this rapidly evolving field is important. Areas Covered Recent next-generation sequencing studies in head and neck squamous cell carcinoma, targeted therapy clinical trials involving head and neck squamous cell carcinoma. Expert Commentary This review discusses the current state of head and neck cancer treatment, and considerations and implications for the incorporation of personalized medicine and targeted therapy for head and neck cancers in a dynamic clinical landscape. PMID:28251187

  4. Clinical pancreatic islet transplantation.

    PubMed

    Shapiro, A M James; Pokrywczynska, Marta; Ricordi, Camillo

    2017-05-01

    Clinical pancreatic islet transplantation can be considered one of the safest and least invasive transplant procedures. Remarkable progress has occurred in both the technical aspects of islet cell processing and the outcomes of clinical islet transplantation. With >1,500 patients treated since 2000, this therapeutic strategy has moved from a curiosity to a realistic treatment option for selected patients with type 1 diabetes mellitus (that is, those with hypoglycaemia unawareness, severe hypoglycaemic episodes and glycaemic lability). This Review outlines the techniques required for human islet isolation, in vitro culture before the transplant and clinical islet transplantation, and discusses indications, optimization of recipient immunosuppression and management of adjunctive immunomodulatory and anti-inflammatory strategies. The potential risks, long-term outcomes and advances in treatment after the transplant are also discussed to further move this treatment towards becoming a more widely available option for patients with type 1 diabetes mellitus and eventually a potential cure.

  5. Dysregulated GPCR Signaling and Therapeutic Options in Uveal Melanoma

    PubMed Central

    Chua, Vivian; Lapadula, Dominic; Randolph, Clinita; Benovic, Jeffrey L.; Wedegaertner, Philip; Aplin, Andrew E.

    2017-01-01

    Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults and arises from the transformation of melanocytes in the uveal tract. Even after treatment of the primary tumor, up to 50% of patients succumb to metastatic disease. The liver is the predominant organ of metastasis. There is an important need to provide effective treatment options for advanced stage UM. In order to provide the preclinical basis for new treatments, it is important to understand the molecular underpinnings of the disease. Recent genomic studies have shown that mutations within components of G protein-coupled receptor (GPCR) signaling are early events associated with ~98% of UMs. Implications This review discusses the alterations in GPCR signaling components (GNAQ and GNA11), dysregulated GPCR signaling cascades, and viable targeted therapies with the intent to provide insight into new therapeutic strategies in UM. PMID:28223438

  6. Advanced basal cell carcinoma, the hedgehog pathway, and treatment options – role of smoothened inhibitors

    PubMed Central

    Fecher, Leslie A; Sharfman, William H

    2015-01-01

    Cutaneous basal cell carcinoma (BCC) is the most common human cancer and its incidence is rising worldwide. Ultraviolet radiation exposure, including tanning bed use, as well as host factors play a role in its development. The majority of cases are treated and cured with local therapies including surgery. Yet, the health care costs of diagnosis and treatment of BCCs in the US is substantial. In the United States, the cost of nonmelanoma skin cancer care in the Medicare population is estimated to be US$426 million per year. While rare, locally advanced BCCs that can no longer be controlled with surgery and/or radiation, and metastatic BCCs do occur and can be associated with significant morbidity and mortality. Vismodegib (GDC-0449), a smoothened inhibitor targeted at the hedgehog pathway, is the first US Food and Drug Association (FDA)-approved agent in the treatment of locally advanced, unresectable, and metastatic BCCs. This class of agents appears to be changing the survival rates in advanced BCC patients, but appropriate patient selection and monitoring are important. Multidisciplinary assessments are essential for the optimal care and management of these patients. For some patients with locally advanced BCC, treatment with a hedgehog inhibitor may eliminate the need for an excessively disfiguring or morbid surgery. PMID:26604681

  7. Ethical, moral, and theological insights into advances in male pediatric and adolescent fertility preservation.

    PubMed

    Ramstein, J J; Halpern, J; Gadzinski, A J; Brannigan, R E; Smith, J F

    2017-07-01

    The successful treatment of boys with cancer has led to increasing attention to preserving their quality of life after completing cancer therapy. One of the top priorities for living a full life is keeping open the opportunity to have children. While sperm banking for males facing sterilizing cancer treatment can be effective, this approach requires subsequent use of reproductive procedures such as in vitro fertilization (IVF) or intrauterine insemination (IUI) to achieve a pregnancy. Advances in fertility preservation techniques may allow pre-pubertal boys to conceive using advanced stem cell technologies and stem cell transplantation in the future. This review summarizes the ethical positions of leading medical societies and explores the religious and moral stances of major religious institutions regarding these options. © 2017 American Society of Andrology and European Academy of Andrology.

  8. Laser immunotherapy for treatment of patients with advanced breast cancer and melanoma

    NASA Astrophysics Data System (ADS)

    Li, Xiaosong; Hode, Tomas; Guerra, Maria C.; Ferrel, Gabriela L.; Nordquist, Robert E.; Chen, Wei R.

    2011-02-01

    Laser immunotherapy (LIT) was developed for the treatment of metastatic tumors. It combines local selective photothermal interaction and active immunological stimulation to induce a long-term, systemic anti-tumor immunity. During the past sixteen years, LIT has been advanced from bench-top to bedside, with promising outcomes. In our pre-clinical and preliminary clinical studies, LIT has demonstrated the capability in inducing immunological responses, which not only can eradicate the treated primary tumors, but also can eliminate untreated metastases at distant sites. Specifically, LIT has been used to treat advanced melanoma and breast cancer patients during the past five years. LIT was shown to be effective in controlling both primary tumors and distant metastases in late-stage patients, who have failed conventional therapies such as surgery, chemotherapy, radiation, and other more advanced approaches. The methodology and the development of LIT are presented in this paper. The patients' responses to LIT are also reported in this paper. The preliminary results obtained in these studies indicated that LIT could be an effective modality for the treatment of patients with late-stage, metastatic cancers, who are facing severely limited options.

  9. Advanced abdominal pregnancy: an increasingly challenging clinical concern for obstetricians

    PubMed Central

    Huang, Ke; Song, Lei; Wang, Longxia; Gao, Zhiying; Meng, Yuanguang; Lu, Yanping

    2014-01-01

    Advanced abdominal pregnancy is rare. The low incidence, high misdiagnosis rate, and lack of specific clinical signs and symptoms explain the fact that there are no standard diagnostic and treatment options available for advanced abdominal pregnancy. We managed a case of abdominal pregnancy in a woman who was pregnant for the first time. This case was further complicated by a concurrent singleton intrauterine pregnancy; the twin pregnancy was not detected until 20 weeks of pregnancy. The case was confirmed at 26 weeks gestational age using MRI to be an abdominal combined with intrauterine pregnancy. The pregnancy was terminated by cesarean section at 33 + 5 weeks gestation. We collected the relevant data of the case while reviewing the advanced abdominal pregnancy-related English literature in the Pubmed, Proquest, and OVID databases. We compared and analyzed the pregnancy history, gestational age when the diagnosis was confirmed, the placental colonization position, the course of treatment and surgical processes, related concurrency rate, post-operative drug treatment programs, and follow-up results with the expectation to provide guidance for other physicians who might encounter similar cases. PMID:25337188

  10. Epidemiology and treatment of hepatocellular carcinoma in Thailand.

    PubMed

    Chonprasertsuk, Soonthorn; Vilaichone, Ratha-Korn

    2017-04-01

    Hepatocellular carcinoma (HCC) is the most frequent type of malignant liver tumor in Thailand. The high incidence rate of HCC reflects from chronic HBV infection in this endemic area. Some patients are asymptomatic at presentation whereas many of them presented at advanced stage of HCC with limited treatment options and grave outcome. The Barcelona Clinic Liver Cancer (BCLC) staging system and management allocation for HCC is widely accepted and used in many international guidelines including Thailand. Curative treatment is expected in early stage of HCC while palliative treatment, combination treatment and best supportive care are offered to advanced stage of HCC. The most effective strategy to prevent the development of HCC is prevention of HBV vertical transmission and treatment HBV or HCV infection. The purpose of this article is to update information of HCC in Thailand including epidemiology, diagnosis, clinical manifestation, and treatment. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Current treatment options for recurrent/metastatic head and neck cancer: a post-ASCO 2011 update and review of last year's literature.

    PubMed

    Kurzweg, T; Möckelmann, N; Laban, S; Knecht, R

    2012-10-01

    The majority of patients with a squamous cell carcinoma of the head and neck present with locally advanced tumors. The first-line treatment of locally advanced tumor stages consists of a combined modality management. Despite these aggressive protocols, many patients develop locoregional recurrences or metastasis and place particularly high demands on the interdisciplinary treatment team. Treatment with a curative intent must be differentiated from a palliative one. In addition to prior treatment, resectability, age and performance status, patient wishes must be taken into consideration in treatment planning, especially considering that most therapies offer little to no overall survival benefit. Salvage surgery, chemo- and target therapies, and reirradiation are head and neck surgeon's and radiooncologist's weapons in the fight against these strong opponents. This review focuses on publications and meeting news from last year and reviews the current status of the clinical application of each treatment modality in recurrent or metastatic head and neck cancer.

  12. Pediatric genetic macular and choroidal diseases

    PubMed Central

    Bergman, Mica Y.; Nallasamy, Sudha

    2014-01-01

    Genetic diseases of the macula and choroid have various inheritance patterns and varying degrees of impact on vision. Herein, we review the literature including most recent advances in the understanding of the genetics of these diseases. Although many of these disorders have limited treatment options, knowledge of inheritance patterns can aid in early detection and with close monitoring can help the ophthalmologist preserve as much vision as possible (for example with early treatment of choroidal neovascularization). PMID:27625881

  13. Interventions for Hip Pain in the Maturing Athlete

    PubMed Central

    Gomberawalla, M. Mustafa; Kelly, Bryan T.; Bedi, Asheesh

    2014-01-01

    Context: Femoroacetabular impingement (FAI) alters hip mechanics, results in hip pain, and may lead to secondary osteoarthritis (OA) in the maturing athlete. Hip impingement can be caused by osseous abnormalities in the proximal femur or acetabulum. These impingement lesions may cause altered loads within the hip joint, which result in repetitive collision damage or sheer forces to the chondral surfaces and acetabular labrum. These anatomic lesions and resultant abnormal mechanics may lead to early osteoarthritic changes. Evidence Acquisition: Relevant articles from the years 1995 to 2013 were identified using MEDLINE, EMBASE, and the bibliographies of reviewed publications. Level of Evidence: Level 4. Results: Improvements in hip arthroscopy have allowed FAI to be addressed utilizing the arthroscope. Adequately resecting the underlying osseous abnormalities is essential to improving hip symptomatology and preventing further chondral damage. Additionally, preserving the labrum by repairing the damaged tissue and restoring the suction seal may theoretically help normalize hip mechanics and prevent further arthritic changes. The outcomes of joint-preserving treatment options may be varied in the maturing athlete due to the degree of underlying OA. Irreversible damage to the hip joint may have already occurred in patients with moderate to advanced OA. In the presence of preexisting arthritis, these patients may only experience fair or even poor results after hip arthroscopy, with early conversion to hip replacement. For patients with advanced hip arthritis, total hip arthroplasty remains a treatment option to reliably improve symptoms with good to excellent outcomes and return to low-impact activities. Conclusion: Advances in the knowledge base and treatment techniques of intra-articular hip pain have allowed surgeons to address this complex clinical problem with promising outcomes. Traditionally, open surgical dislocations for hip preservation surgery have shown good long-term results. Improvements in hip arthroscopy have led to outcomes equivalent to open surgery while utilizing significantly less invasive techniques. However, outcomes may ultimately depend on the degree of underlying OA. When counseling the mature athlete with hip pain, an understanding of the underlying anatomy, degree of arthritis, and expectations will help guide the treating surgeon in offering appropriate treatment options. PMID:24427445

  14. Clostridium difficile infection: management strategies for a difficult disease

    PubMed Central

    Pardi, Darrell S.

    2014-01-01

    Clostridium difficile was first described as a cause of diarrhea in 1978 and in the last three decades has reached an epidemic state with increasing incidence and severity in both healthcare and community settings. There also has been a rise in severe outcomes from C. difficile infection (CDI). There have been tremendous advancements in the field of CDI with the identification of newer risk factors, recognition of CDI in populations previously thought not at risk and development of better diagnostic modalities. Several treatment options are available for CDI apart from metronidazole and vancomycin, and include new drugs such as fidaxomicin and other options such as fecal microbiota transplantation. This review discusses the epidemiology, risk factors and outcomes from CDI, and focuses primarily on existing and evolving treatment modalities. PMID:24587820

  15. Surgical treatment and management of the severely burn patient: Review and update.

    PubMed

    Gacto-Sanchez, P

    Since one of the main challenges in treating acute burn injuries is preventing infection, early excising of the eschar and covering of the wound becomes critical. Non-viable tissue is removed by initial aggressive surgical debridement. Many surgical options for covering the wound bed have been described, although split-thickness skin grafts remain the standard for the rapid and permanent closure of full-thickness burns. Significant advances made in the past decades have greatly improved burns patient care, as such that major future improvements in survival rates seem to be more difficult. Research into stem cells, grafting, biomarkers, inflammation control, and rehabilitation will continue to improve individualized care and create new treatment options for these patients. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  16. Controversy about Management of Hydrocephalus - Shunt vs. Endoscopic Third Ventriculostomy.

    PubMed

    Kumar, Vikas; Bodeliwala, Shaam; Singh, Daljit

    2017-08-01

    The best management of hydrocephalus is still controversial in the twenty-first century. Shunt treatment for hydrocephalus is the most common procedure performed in neurosurgical practice and is associated with the highest complications rate. But during the last 2 decades, the treatment of hydrocephalus has improved with better shunt devices available today, increased facilities for investigations and newer approaches like endoscopic third ventriculostomy. The recent advances in development of better endoscopes have provided the patient and treating doctor with an option for an alternative surgery for treatment of hydrocephalus.

  17. Adjunctive Treatment in Juvenile Nasopharyngeal Angiofibroma: How Should We Approach Recurrence?

    PubMed

    Scholfield, Daniel W; Brundler, Marie-Anne; McDermott, Ann-Louise; Mussai, Francis; Kearns, Pamela

    2016-04-01

    A recent case of advanced, recurrent juvenile nasopharyngeal angiofibroma (JNA) at our institution has highlighted the limited evidence regarding adjunctive treatment. We present the case of a 10-year-old boy who is the first to undergo multiple-staged surgical resections alongside vincristine treatment. We performed a review of the literature analyzing the roles of radiation therapy, cytotoxic drugs, and novel targeted agents in JNA relapse. Small cohort studies suggest radiotherapy and flutamide are the most rational treatment options for residual and recurrent JNA. Our review highlights the need for further research into the management of primary and recurrent JNA.

  18. Percutaneous CT-Guided Cryoablation as an Alternative Treatment for an Extensive Pelvic Bone Giant Cell Tumor.

    PubMed

    Panizza, Pedro Sergio Brito; de Albuquerque Cavalcanti, Conrado Furtado; Yamaguchi, Nise Hitomi; Leite, Claudia Costa; Cerri, Giovanni Guido; de Menezes, Marcos Roberto

    2016-02-01

    A giant cell tumor (GCT) is an intermediate grade, locally aggressive neoplasia. Despite advances in surgical and clinical treatments, cases located on the spine and pelvic bones remain a significant challenge. Failure of clinical treatment with denosumab and patient refusal of surgical procedures (hemipelvectomy) led to the use of cryoablation. We report the use of percutaneous CT-guided cryoablation as an alternative treatment, shown to be a minimally invasive, safe, and effective option for a GCT with extensive involvement of the pelvic bones and allowed structural and functional preservation of the involved bones.

  19. Percutaneous CT-Guided Cryoablation as an Alternative Treatment for an Extensive Pelvic Bone Giant Cell Tumor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Panizza, Pedro Sergio Brito; Albuquerque Cavalcanti, Conrado Furtado de; Yamaguchi, Nise Hitomi

    2016-02-15

    A giant cell tumor (GCT) is an intermediate grade, locally aggressive neoplasia. Despite advances in surgical and clinical treatments, cases located on the spine and pelvic bones remain a significant challenge. Failure of clinical treatment with denosumab and patient refusal of surgical procedures (hemipelvectomy) led to the use of cryoablation. We report the use of percutaneous CT-guided cryoablation as an alternative treatment, shown to be a minimally invasive, safe, and effective option for a GCT with extensive involvement of the pelvic bones and allowed structural and functional preservation of the involved bones.

  20. Treatment of the neglected Achilles tendon rupture.

    PubMed

    Bevilacqua, Nicholas J

    2012-04-01

    Achilles tendon ruptures are best managed acutely. Neglected Achilles tendon ruptures are debilitating injuries and the increased complexity of the situation must be appreciated. Surgical management is recommended, and only in the poorest surgical candidate is conservative treatment entertained. Numerous treatment algorithms and surgical techniques have been described. A V-Y advancement flap and flexor halluces longus tendon transfer have been found to be reliable and achieve good clinical outcomes for defects ranging from 2 cm to 8 cm. This article focuses on the treatment options for the neglected Achilles tendon rupture. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. SGLT2 inhibitors: a promising new therapeutic option for treatment of type 2 diabetes mellitus.

    PubMed

    Misra, Monika

    2013-03-01

    Hyperglycemia is an important pathogenic component in the development of microvascular and macrovascular complications in type 2 diabetes mellitus. Inhibition of renal tubular glucose reabsorption that leads to glycosuria has been proposed as a new mechanism to attain normoglycemia and thus prevent and diminish these complications. Sodium glucose cotransporter 2 (SGLT2) has a key role in reabsorption of glucose in kidney. Competitive inhibitors of SGLT2 have been discovered and a few of them have also been advanced in clinical trials for the treatment of diabetes. To discuss the therapeutic potential of SGLT2 inhibitors currently in clinical development. A number of preclinical and clinical studies of SGLT2 inhibitors have demonstrated a good safety profile and beneficial effects in lowering plasma glucose levels, diminishing glucotoxicity, improving glycemic control and reducing weight in diabetes. Of all the SGLT2 inhibitors, dapagliflozin is a relatively advanced compound with regards to clinical development. SGLT2 inhibitors are emerging as a promising therapeutic option for the treatment of diabetes. Their unique mechanism of action offers them the potential to be used in combination with other oral anti-diabetic drugs as well as with insulin. © 2012 The Author. JPP © 2012 Royal Pharmaceutical Society.

  2. Clinical roundtable monograph: Recent advances in taxanes for the first-line treatment of advanced non-small cell lung cancer.

    PubMed

    Socinski, Mark A; Govindan, Ramaswamy; Spigel, David

    2012-10-01

    Treatments for non-small cell lung cancer (NSCLC) are based on the broad categories of squamous or non-squamous histology. Frontline treatment options include pemetrexed and cisplatin, pemetrexed and a taxane, gemcitabine with cisplatin, and the addition of bevacizumab to a taxane and carboplatin. Pemetrexed is used for maintenance therapy for non-squamous NSCLC, whereas patients with squamous NSCLC lack easy options for maintenance therapy. nab-Paclitaxel overcomes the solubility and toxicity issues of solvent-based paclitaxel, and the albumin in nab-paclitaxel improves the concentration of the drug in the tumor. A recent phase III trial in NSCLC compared nab-paclitaxel with carboplatin versus solvent-based paclitaxel with carboplatin, and found improved overall response rates (ORRs) in the nab-paclitaxel arm (33% vs 25%; P=.005). In a subset analysis, NSCLC patients with squamous histology had a higher ORR (41%) with nab-paclitaxel than with solvent-based paclitaxel (24%; P<.001). Another subset analysis found that patients ages 70 years and older had improved overall survival (median 19.9 months) with nab-paclitaxel compared with solvent-based paclitaxel (median 10.4 months; P=.009). Patients in the nab-paclitaxel arm had less neuropathy, less hearing loss, and fewer interruptions in daily living than patients in the solvent-based paclitaxel arm.

  3. Turning the Lens Inward: Cultural Competence and Providers' Values in Health Care Decision Making

    ERIC Educational Resources Information Center

    Chettih, Mindy

    2012-01-01

    The population of older adults in the United States is growing in size and diversity, presenting challenges to health care providers and patients in the context of health care decision making (DM), including obtaining informed consent for treatment, advance care planning, and deliberations about end-of-life care options. Although existing…

  4. Bevacizumab plus interferon-α versus sunitinib for first-line treatment of renal cell carcinoma in Italy: a cost-minimization analysis.

    PubMed

    Ravasio, Roberto; Ortega, Cinzia; Sabbatini, Roberto; Porta, Camillo

    2011-01-01

    Renal cell carcinoma (RCC) is the most common form of kidney cancer. Immunotherapy with interferon-α (IFNα) and interleukin-2 (IL-2) has been the historical therapy of choice for the treatment of locally advanced or metastatic RCC prior to the more recent development of targeted therapies, including sunitinib and bevacizumab (combined with IFNα). Clinically and statistically significant advantages have been shown with both sunitinib and the combination of bevacizumab + IFNα versus IFNα alone in the treatment of advanced or metastatic RCC. The present study evaluated the incremental costs of bevacizumab + IFNα versus sunitinib for the first-line treatment of advanced or metastatic RCC assuming similar efficacy for these treatments. The efficacy profiles of bevacizumab + IFNα or sunitinib alone have been shown (indirectly) to be similar in patients with RCC; indeed, median progression-free survival (PFS) with either treatment is in the 10- to 11-month range. Therefore, a cost-minimization analysis was performed, focusing on direct medical costs only (drugs, administration and management of adverse events). The analysis considered the perspective of the Italian National Health Service (NHS), comparing the cost of bevacizumab (10 mg/kg) plus IFNα (9, 6 or 3 million IU [MIU]) versus sunitinib (50 mg) as first-line therapies for advanced or metastatic clear-cell RCC. The average cost per treated patient (year 2010 values) was assessed for the two treatment options at 11 months (median PFS). Assuming a PFS of 11 months for both treatment options, bevacizumab + IFNα (9 MIU) would be a lower cost strategy (cost savings of €2052 per patient) than sunitinib. This difference arises mainly from the reduction in the acquisition cost of bevacizumab to the NHS (risk-sharing agreement). The cost advantages for bevacizumab would increase in parallel with a reduction in IFNα dosing; for example, with IFNα 6 MIU the corresponding cost savings would be €4185, and with 3 MIU the cost advantage would be €6320 per patient. This analysis suggests that bevacizumab + IFNα is a cost-saving alternative to sunitinib in the treatment of first-line metastatic RCC. Its superior safety profile also meant that the cost of managing adverse events was lower for bevacizumab + IFNα than for sunitinib.

  5. Safety and clinical efficacy of everolimus in the treatment of advanced renal cell carcinoma (RCC)

    PubMed Central

    Shahani, Rohan; Kwan, Kevin G; Kapoor, Anil

    2010-01-01

    Renal cell carcinoma (RCC) is one of the most lethal genitourinary malignancies. Recently, there has been a paradigm shift in the management of advanced RCC. New targeted therapies including vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors have been developed which have shown promising results in a patient population who otherwise had very few options for treatment. The first mTOR inhibitor, temsirolimus, an intravenous prodrug, has shown improved overall survival in poor prognosis patients. More recently, an oral mTOR inhibitor, everolimus (RAD 001), has been developed which has been shown to delay disease progression in patients with metastatic RCC who have progressed on other targeted therapies. Although a survival advantage in phase III trials is seen with everolimus, associated systemic toxicities, while generally well tolerated, are not insignificant. These include mucositis, hyperglycemia, hyperlipidemia, and pneumonitis. Despite the side effects, emerging evidence points to everolimus as the optimal second-line treatment for patients with advanced renal cell carcinoma. PMID:21701620

  6. Advances in the Molecular Analysis of Breast Cancer: Pathway Toward Personalized Medicine.

    PubMed

    Rosa, Marilin

    2015-04-01

    Breast cancer is a heterogeneous disease that encompasses a wide range of clinical behaviors and histological and molecular variants. It is the most common type of cancer affecting women worldwide and is the second leading cause of cancer death. A comprehensive literature search was performed to explore the advances in molecular medicine related to the diagnosis and treatment of breast cancer. During the last few decades, advances in molecular medicine have changed the landscape of cancer treatment as new molecular tests complement and, in many instances, exceed traditional methods for determining patient prognosis and response to treatment options. Personalized medicine is becoming the standard of care around the world. Developments in molecular profiling, genomic analysis, and the discovery of targeted drug therapies have significantly improved patient survival rates and quality of life. This review highlights what pathologists need to know about current molecular tests for classification and prognostic/ predictive assessment of breast carcinoma as well as their role as part of the medical team.

  7. Integrated nitrogen removal biofilter system with ceramic membrane for advanced post-treatment of municipal wastewater.

    PubMed

    Son, Dong-Jin; Yun, Chan-Young; Kim, Woo-Yeol; Zhang, Xing-Ya; Kim, Dae-Gun; Chang, Duk; Sunwoo, Young; Hong, Ki-Ho

    2016-12-01

    The pre-denitrification biofilm process for nitrogen removal was combined with ceramic membrane with pore sizes of 0.05-0.1 µm as a system for advanced post-treatment of municipal wastewater. The system was operated under an empty bed hydraulic retention time of 7.8 h, recirculation ratio of 3, and transmembrane pressure of 0.47 bar. The system showed average removals of organics, total nitrogen, and solids as high as 93%, 80%, and 100%, respectively. Rapid nitrification could be achieved and denitrification was performed in the anoxic filter without external carbon supplements. The residual particulate organics and nitrogen in effluent from biofilm process could be also removed successfully through membrane filtration and the removal of total coliform was noticeably improved after membrane filtration. Thus, a system composed of the pre-denitrification biofilm process with ceramic membrane would be a compact and flexible option for advanced post-treatment of municipal wastewater.

  8. Technological advances in the treatment of trauma: a review of promising practices.

    PubMed

    Paul, Lisa A; Hassija, Christina M; Clapp, Joshua D

    2012-11-01

    Given the availability of empirically supported practices for addressing posttraumatic stress disorder and other forms of trauma-related distress, the development and implementation of new technology to deliver these treatments is exciting. Technological innovations in this literature aim to expand availability of empirically based intervention, increase treatment adherence and acceptability, and overcome barriers commonly encountered with conventional trauma-focused treatment. Much of the current research on these technological developments consists of brief reviews and case studies of the separate therapy modalities. Although this work serves to document the appeal and utility of these innovations, it does not provide comprehensive information about the host of options available. To that end, the three general categories of technological advances in trauma therapy (i.e., videoconferencing, e-Health, virtual reality) are reviewed here, including information regarding their empirical support and suggestions for future research and clinical practice.

  9. Pediatric obsessive-compulsive disorder: an update for advanced practice psychiatric nurses.

    PubMed

    Kameg, Kirstyn Marie; Richardson, Luann; Szpak, Janene Luther

    2015-05-01

    Obsessive-compulsive disorder (OCD) may have an onset in childhood or adolescence resulting in significant functional impairment and disability into adulthood. There are frequently developmental differences in the content of the obsessions and compulsions in youth compared to adults. Lack of insight or shame may result in failure of the youth to seek treatment. This delay in treatment may lead to the development of other psychiatric comorbidities, including suicide. Evidence-based treatments for OCD include cognitive behavioral therapy and exposure/response prevention, and in moderate to severe cases, use of selective serotonin reuptake inhibitors is indicated. Advanced practice psychiatric nurses are in a unique position to provide psychoeducation, psychotherapy, and medications, if indicated, to youth with this condition to improve functioning and reduce morbidity and mortality. This article will provide an overview of the diagnostic criteria for OCD, etiologies, assessment strategies, differential diagnoses, common comorbidities, and evidence-based treatment options. © 2015 Wiley Periodicals, Inc.

  10. Navigating the current landscape of clinical genetic testing for inherited retinal dystrophies.

    PubMed

    Lee, Kristy; Garg, Seema

    2015-04-01

    Inherited eye disorders are a significant cause of vision loss. Genetic testing can be particularly helpful for patients with inherited retinal dystrophies because of genetic heterogeneity and overlapping phenotypes. The need to identify a molecular diagnosis for retinal dystrophies is particularly important in the era of developing novel gene therapy-based treatments, such as the RPE65 gene-based clinical trials and others on the horizon, as well as recent advances in reproductive options. The introduction of massively parallel sequencing technologies has significantly advanced the identification of novel gene candidates and has expanded the landscape of genetic testing. In a relatively short time clinical medicine has progressed from limited testing options to a plethora of choices ranging from single-gene testing to whole-exome sequencing. This article outlines currently available genetic testing and factors to consider when selecting appropriate testing for patients with inherited retinal dystrophies.

  11. Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises.

    PubMed

    Aragon-Ching, Jeanny B; Trump, Donald L

    2016-09-01

    Bladder urothelial cancers remain an important urologic cancer with limited treatment options in the locally advanced and metastatic setting. While neoadjuvant chemotherapy for locally advanced muscle-invasive cancers has shown overall survival benefit, clinical uptake in practice have lagged behind. Controversies surrounding adjuvant chemotherapy use are also ongoing. Systemic therapies for metastatic bladder cancer have largely used platinum-based therapies without effective standard second-line therapy options for those who fail, although vinflunine is approved in Europe as a second-line therapy based on a Phase III trial, and most recently, atezolizumab, a checkpoint inhibitor, was approved by the US FDA. Given increasing recognition of mutational signatures expressed in urothelial carcinomas, several promising agents with use of VEGF-targeted therapies, HER2-directed agents and immunotherapies with PD-1/PD-L1 antibodies in various settings are discussed herein.

  12. Immunotherapy for Head and Neck Squamous Cell Carcinoma: A Review of Current and Emerging Therapeutic Options

    PubMed Central

    Moskovitz, Jessica M.; Moy, Jennifer; Seiwert, Tanguy Y.

    2017-01-01

    Abstract Advances in the field of cancer immunotherapy have occurred rapidly over the past decade. Exciting results from clinical trials have led to new treatment options and improved survival for patients with a myriad of solid tumor pathologies. However, questions remain unanswered regarding duration and timing of therapy, combination regimens, appropriate biomarkers of disease, and optimal monitoring of therapeutic response. This article reviews emerging immunotherapeutic agents and significant clinical trials that have led to advancements in the field of immuno‐oncology for patients with head and neck squamous cell carcinoma. Implications for Practice. This review article summarizes recently developed agents that harness the immune system to fight head and neck squamous cell carcinoma. A brief review of the immune system and its role in cancer development is included. Recently completed and emerging therapeutic trials centering on the immune system and head and neck cancer are reviewed. PMID:28507203

  13. Cetuximab in locally advanced head-and-neck cancer: defining the population

    PubMed Central

    Ho, C.

    2010-01-01

    Encouraging data for targeted therapy in head-and-neck squamous cell carcinoma are opening new options for treatment. Phase III trials of cetuximab, an antibody directed against the epidermal growth factor receptor (egfr) have demonstrated benefit in the locally advanced and metastatic settings. Recognizing the importance of emerging therapies, Cancer Care Ontario published guideline recommendations for egfr-targeted therapy in stage iii and iv head-and-neck cancer. The present paper takes a further look at the population for whom an offer of cetuximab therapy may be appropriate. PMID:20697514

  14. [Targeted therapies in hepatocellular carcinomas: recent results and future development].

    PubMed

    Marijon, H; Faivre, S; Raymond, E

    2009-05-01

    Hepatocellular carcinoma (HCC) is one of the 5th most common cancers around the world with a limited number of systemic therapeutic options. Cytotoxic agents, hormonotherapy and immunotherapy have failed to demonstrate benefit compared to best supportive care in patients with advanced HCC. The recent development of targeted therapies provided hope for the treatment of advanced HCC. We reviewed phases II-III trials presented in 2007 and 2008. Results are promising with a clinical benefit reported with molecular therapies targeting EGF/EGFR and VEGF/VEGFR pathways.

  15. Refractory Hodgkin lymphoma.

    PubMed

    von Tresckow, Bastian; Engert, Andreas

    2013-09-01

    Despite the advances in the treatment of Hodgkin Lymphoma, patients with refractory disease still have a poor prognosis. Hodgkin Lymphoma can be refractory at first diagnosis or might become refractory later in the course of treatment. Both situations represent a therapeutic challenge. Intensified chemotherapy with BEACOPP escalated has been evaluated in early unfavourable and advanced Hodgkin Lymphoma and led to an improved tumour control and reduced rates of refractory disease. Furthermore, there is growing evidence for the role of tandem autologous transplant in breaking refractory disease. For patients relapsing after autologous transplant, more recent analyses have reported outcome and defined risk factors. The antibody drug conjugate brentuximab vedotin is a new, highly effective therapeutic option for these patients. Dose-reduced allogeneic transplant is a therapeutic alternative for patients relapsing after autologous transplant, but induction of a remission is the prerequisite for a successful allogeneic transplant. Brentuximab vedotin has been evaluated as a bridge to allogeneic transplant for patients refractory to conventional treatment. Recent therapeutic advances have improved the prognosis of Hodgkin Lymphoma by prevention or successful treatment of refractory disease. The use of new drugs such as brentuximab vedotin will hopefully further increase the cure rates.

  16. Paclitaxel is safe and effective in the treatment of advanced AIDS-related Kaposi's sarcoma.

    PubMed

    Gill, P S; Tulpule, A; Espina, B M; Cabriales, S; Bresnahan, J; Ilaw, M; Louie, S; Gustafson, N F; Brown, M A; Orcutt, C; Winograd, B; Scadden, D T

    1999-06-01

    Liposomal anthracyclines are the present standard treatment for advanced AIDS-related Kaposi's sarcoma (KS). No effective therapies have been defined for use after treatment failure of these agents. A phase II trial was thus conducted with paclitaxel in patients with advanced KS to assess safety and antitumor activity. A regimen of paclitaxel at a dose of 100 mg/m(2) was given every 2 weeks to patients with advanced AIDS-related KS. Patients were treated until complete remission, disease progression, or unacceptable toxicity occurred. Fifty-six patients with advanced AIDS-related KS were accrued. Tumor-associated edema was present in 70% of patients and visceral involvement in 45%. Forty patients (71%) had received prior systemic therapy; 31 of these were resistant to an anthracycline. The median entry CD4(+) lymphocyte count was 20 cells/mm(3) (range, 0 to 358). A median of 10 cycles (range, 1 to 54+) of paclitaxel was administered. Fifty-nine percent of patients showed complete (n = 1) or partial response (n = 32) to paclitaxel. The median duration of response was 10.4 months (range, 2.8 to 26.7+ months) and the median survival was 15.4 months. The main side effects of therapy were grade 3 or 4 neutropenia in 61% of patients and mild-to-moderate alopecia in 87%. Paclitaxel at 100 mg/m(2) given every 2 weeks is active and well tolerated in the treatment of advanced and previously treated AIDS-related KS. The median duration of response is among the longest observed for any regimen or single agent reported for AIDS-related KS. Paclitaxel at this dosage and schedule is a treatment option for patients with advanced AIDS-related KS, including those who have experienced treatment failure of prior systemic therapy.

  17. A model for emergency department end-of-life communications after acute devastating events--part I: decision-making capacity, surrogates, and advance directives.

    PubMed

    Limehouse, Walter E; Feeser, V Ramana; Bookman, Kelly J; Derse, Arthur

    2012-09-01

    Making decisions for a patient affected by sudden devastating illness or injury traumatizes a patient's family and loved ones. Even in the absence of an emergency, surrogates making end-of-life treatment decisions may experience negative emotional effects. Helping surrogates with these end-of-life decisions under emergent conditions requires the emergency physician (EP) to be clear, making medical recommendations with sensitivity. This model for emergency department (ED) end-of-life communications after acute devastating events comprises the following steps: 1) determine the patient's decision-making capacity; 2) identify the legal surrogate; 3) elicit patient values as expressed in completed advance directives; 4) determine patient/surrogate understanding of the life-limiting event and expectant treatment goals; 5) convey physician understanding of the event, including prognosis, treatment options, and recommendation; 6) share decisions regarding withdrawing or withholding of resuscitative efforts, using available resources and considering options for organ donation; and 7) revise treatment goals as needed. Emergency physicians should break bad news compassionately, yet sufficiently, so that surrogate and family understand both the gravity of the situation and the lack of long-term benefit of continued life-sustaining interventions. EPs should also help the surrogate and family understand that palliative care addresses comfort needs of the patient including adequate treatment for pain, dyspnea, or anxiety. Part I of this communications model reviews determination of decision-making capacity, surrogacy laws, and advance directives, including legal definitions and application of these steps; Part II (which will appear in a future issue of AEM) covers communication moving from resuscitative to end-of-life and palliative treatment. EPs should recognize acute devastating illness or injuries, when appropriate, as opportunities to initiate end-of-life discussions and to implement shared decisions. © 2012 by the Society for Academic Emergency Medicine.

  18. Genome editing: the breakthrough technology for inherited retinal disease?

    PubMed

    Smith, Andrew J; Carter, Stephen P; Kennedy, Breandán N

    2017-10-01

    Genetic alterations resulting in a dysfunctional retinal pigment epithelium and/or degenerating photoreceptors cause impaired vision. These juxtaposed cells in the retina of the posterior eye are crucial for the visual cycle or phototransduction. Deficits in these biochemical processes perturb neural processing of images capturing the external environment. Notably, there is a distinct lack of clinically approved pharmacological, cell- or gene-based therapies for inherited retinal disease. Gene editing technologies are rapidly advancing as a realistic therapeutic option. Areas covered: Recent discovery of endonuclease-mediated gene editing technologies has culminated in a surge of investigations into their therapeutic potential. In this review, the authors discuss gene editing technologies and their applicability in treating inherited retinal diseases, the limitations of the technology and the research obstacles to overcome before editing a patient's genome becomes a viable treatment option. Expert opinion: The ability to strategically edit a patient's genome constitutes a treatment revolution. However, concerns remain over the safety and efficacy of either transplanting iPSC-derived retinal cells following ex vivo gene editing, or with direct gene editing in vivo. Ultimately, further refinements to improve efficacy and safety profiles are paramount for gene editing to emerge as a widely available treatment option.

  19. The genetics of age-related macular degeneration (AMD)--Novel targets for designing treatment options?

    PubMed

    Grassmann, Felix; Fauser, Sascha; Weber, Bernhard H F

    2015-09-01

    Age-related macular degeneration (AMD) is a progressive disease of the central retina and the main cause of legal blindness in industrialized countries. Risk to develop the disease is conferred by both individual as well as genetic factors with the latter being increasingly deciphered over the last decade. Therapeutically, striking advances have been made for the treatment of the neovascular form of late stage AMD while for the late stage atrophic form of the disease, which accounts for almost half of the visually impaired, there is currently no effective therapy on the market. This review highlights our current knowledge on the genetic architecture of early and late stage AMD and explores its potential for the discovery of novel, target-guided treatment options. We reflect on current clinical and experimental therapies for all forms of AMD and specifically note a persisting lack of efficacy for treatment in atrophic AMD. We further explore the current insight in AMD-associated genes and pathways and critically question whether this knowledge is suited to design novel treatment options. Specifically, we point out that known genetic factors associated with AMD govern the risk to develop disease and thus may not play a role in its severity or progression. Treatments based on such knowledge appear appropriate rather for prevention than treatment of manifest disease. As a consequence, future research in AMD needs to be greatly focused on approaches relevant to the patients and their medical needs. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Implementing an advanced waste separation step in an MBT plant: assessment of technical, economic and environmental impacts.

    PubMed

    Meirhofer, Martina; Piringer, Gerhard; Rixrath, Doris; Sommer, Manuel; Ragossnig, Arne Michael

    2013-10-01

    Heavy fractions resulting from mechanical treatment stages of mechanical-biological waste treatment plants are posing very specific demands with regard to further treatment (large portions of inert and high-caloric components). Based on the current Austrian legal situation such a waste stream cannot be landfilled and must be thermally treated. The aim of this research was to evaluate if an inert fraction generated from this waste stream with advanced separation technologies, two sensor-based [near-infrared spectroscopy (NIR), X-ray transmission (XRT)] and two mechanical systems (wet and dry) is able to be disposed of. The performance of the treatment options for separation was evaluated by characterizing the resulting product streams with respect to purity and yield. Complementing the technical evaluation of the processing options, an assessment of the economic and global warming effects of the change in waste stream routing was conducted. The separated inert fraction was evaluated with regard to landfilling. The remaining high-caloric product stream was evaluated with regard to thermal utilization. The results show that, in principal, the selected treatment technologies can be used to separate high-caloric from inert components. Limitations were identified with regard to the product qualities achieved, as well as to the economic expedience of the treatment options. One of the sensor-based sorting systems (X-ray) was able to produce the highest amount of disposeable heavy fraction (44.1%), while having the lowest content of organic (2.0% C biogenic per kg waste input) components. None of the high-caloric product streams complied with the requirements for solid recovered fuels as defined in the Austrian Ordinance on Waste Incineration. The economic evaluation illustrates the highest specific treatment costs for the XRT (€ 23.15 per t), followed by the NIR-based sorting system (€ 15.67 per t), and the lowest costs for the air separation system (€ 10.79 per t). Within the ecological evaluation it can be shown that the results depend strongly on the higher heating value of the high caloric light fraction and on the content of C biogenic of the heavy fraction. Therefore, the XRT system had the best results for the overall GWP [-14 kg carbon dioxide equivalents (CO2 eq) per t of input waste] and the NIR-based the worst (193 kg CO2 eq per t of input waste). It is concluded that three of the treatment options would be suitable under the specific conditions considered here. Of these, sensor-based sorting is preferable owing to its flexibility.

  1. Towards an optimal treatment algorithm for metastatic pancreatic ductal adenocarcinoma (PDA)

    PubMed Central

    Uccello, M.; Moschetta, M.; Mak, G.; Alam, T.; Henriquez, C. Murias; Arkenau, H.-T.

    2018-01-01

    Chemotherapy remains the mainstay of treatment for advanced pancreatic ductal adenocarcinoma (pda). Two randomized trials have demonstrated superiority of the combination regimens folfirinox (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) and gemcitabine plus nab-paclitaxel over gemcitabine monotherapy as a first-line treatment in adequately fit subjects. Selected pda patients progressing to first-line therapy can receive secondline treatment with moderate clinical benefit. Nevertheless, the optimal algorithm and the role of combination therapy in second-line are still unclear. Published second-line pda clinical trials enrolled patients progressing to gemcitabine-based therapies in use before the approval of nab-paclitaxel and folfirinox. The evolving scenario in second-line may affect the choice of the first-line treatment. For example, nanoliposomal irinotecan plus 5-fluouracil and leucovorin is a novel second-line option which will be suitable only for patients progressing to gemcitabine-based therapy. Therefore, clinical judgement and appropriate patient selection remain key elements in treatment decision. In this review, we aim to illustrate currently available options and define a possible algorithm to guide treatment choice. Future clinical trials taking into account sequential treatment as a new paradigm in pda will help define a standard algorithm. PMID:29507500

  2. Treatment of advanced colorectal cancer (CRC) in daily practice: results of a survey in two Italian regions, Piemonte and Valle d'Aosta.

    PubMed

    Comandone, A; Berardo, R; Faggiuolo, R; Boglione, A; Bergnolo, P; Dal Canton, O; Di Napoli, A; Oliva, C; Bumma, C

    1998-01-01

    Colorectal cancer (CRC) is one of the most important health problems in Western countries: it is the fourth cancer in terms of incidence and the second cause of cancer death. Surgery is the main therapeutic choice and there is broad consensus on the role of adjuvant chemotherapy (CT) after resection. Unfortunately, 50% of the patients will relapse and die of the disease. Palliative CT based on 5-fluorouracil (5FU) may induce a 9-48% response rate with a median survival of 11.5 months. At present there is no gold standard for CT In advanced CRC and the situation has become more complicated since the advent of new drugs (Raltitrexed, Irinotecan, Oxaliplatin). The aim of this study was the identification of the different approaches to treatment of advanced CRC among the clinicians (oncologists, radiologists, internal medicine specialists, surgeons) who practice CT. Forty-six clinicians from two Italian Regions (Piemonte and Valle d'Aosta) were interviewed by telephone. 5FU modulated with Lederfolin according to the classic Machover scheme is the main option in daily practice. More sophisticated therapies are reserved to patients with a good performance status (PS) and are prescribed only in the larger centers. The planned therapies usually consist of six courses. Restaging may be performed after three or six courses. A marked difference has been recorded in the evaluation of a situation of no change (NC): 25.5% of the clinicians evaluate stable disease as a positive result. In the event of disease progression or relapse, 35% of the clinicians do not prescribe second-line CT. In case of further treatment, the options are totally subjective. A national survey on this issue is necessary under the auspices of AIOM (Associazione Italiana Oncologia Medica) and involving oncologists, epidemiologists and statisticians, in order to define the reasons for variations in therapy in advanced CRC and determine the differences between clinicians of different age, specialization and location. This survey could lead to a definition of guidelines for the treatment of advanced CRC.

  3. The Multidisciplinary Management of Colorectal Cancer: Present and Future Paradigms

    PubMed Central

    Sievers, Chelsie K.; Kratz, Jeremy D.; Zurbriggen, Luke D.; LoConte, Noelle K.; Lubner, Sam J.; Uboha, Natalya; Mulkerin, Daniel; Matkowskyj, Kristina A.; Deming, Dustin A.

    2016-01-01

    As treatment strategies for patients with colorectal cancer advance, there has now become an ever-increasing need for multidisciplinary teams to care for these patients. Recent investigations into the timing and duration of perioperative therapy, as well as, the rise of molecular profiling have led to more systemic chemotherapeutic options. The most efficacious use, in terms of timing and patient selection, of these therapies in the setting of modern operative and radiotherapy techniques requires the generation of care teams discussing cases at multidisciplinary conferences. This review highlights the role of multidisciplinary team conferences, advances in perioperative chemotherapy, current clinical biomarkers, and emerging therapeutic agents for molecular subtypes of metastatic colon cancer. As our understanding of relevant molecular subtypes increases and as data becomes available on treatment response, the treatment of colorectal cancer will become more precise and effective. PMID:27582648

  4. The Multidisciplinary Management of Colorectal Cancer: Present and Future Paradigms.

    PubMed

    Sievers, Chelsie K; Kratz, Jeremy D; Zurbriggen, Luke D; LoConte, Noelle K; Lubner, Sam J; Uboha, Natalya; Mulkerin, Daniel; Matkowskyj, Kristina A; Deming, Dustin A

    2016-09-01

    As treatment strategies for patients with colorectal cancer advance, there has now become an ever-increasing need for multidisciplinary teams to care for these patients. Recent investigations into the timing and duration of perioperative therapy, as well as, the rise of molecular profiling have led to more systemic chemotherapeutic options. The most efficacious use, in terms of timing and patient selection, of these therapies in the setting of modern operative and radiotherapy techniques requires the generation of care teams discussing cases at multidisciplinary conferences. This review highlights the role of multidisciplinary team conferences, advances in perioperative chemotherapy, current clinical biomarkers, and emerging therapeutic agents for molecular subtypes of metastatic colon cancer. As our understanding of relevant molecular subtypes increases and as data becomes available on treatment response, the treatment of colorectal cancer will become more precise and effective.

  5. Recent advancements in bioremediation of dye: Current status and challenges.

    PubMed

    Vikrant, Kumar; Giri, Balendu Shekhar; Raza, Nadeem; Roy, Kangkan; Kim, Ki-Hyun; Rai, Birendra Nath; Singh, Ram Sharan

    2018-04-01

    The rampant industrialization and unchecked growth of modern textile production facilities coupled with the lack of proper treatment facilities have proliferated the discharge of effluents enriched with toxic, baleful, and carcinogenic pollutants including dyes, heavy metals, volatile organic compounds, odorants, and other hazardous materials. Therefore, the development of cost-effective and efficient control measures against such pollution is imperative to safeguard ecosystems and natural resources. In this regard, recent advances in biotechnology and microbiology have propelled bioremediation as a prospective alternative to traditional treatment methods. This review was organized to address bioremediation as a practical option for the treatment of dyes by evaluating its performance and typical attributes. It further highlights the current hurdles and future prospects for the abatement of dyes via biotechnology-based remediation techniques. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Importance of increased intraosseous pressure in the development of osteonecrosis of the femoral head: implications for treatment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hungerford, D.S.; Lennox, D.W.

    1985-10-01

    Early diagnosis of osteonecrosis by radiograph, bone scan, CT scan, magnetic resonance imaging (MRI), intraosseous pressure measurement, or intraosseous venogram can lead to early successful treatment. For early (Ficat stages I and II) osteonecrosis of the hip, core decompression can provide diagnostic confirmation and pain relief and may prevent progression of disease. For more advanced disease (Ficat stages II and IV), osteotomy, endoprosthetic or bipolar prosthetic replacement, total hip arthroplasty, and arthrodesis are surgical options.86 references.

  7. Freezing of gait: Promising avenues for future treatment.

    PubMed

    Gilat, Moran; Lígia Silva de Lima, Ana; Bloem, Bastiaan R; Shine, James M; Nonnekes, Jorik; Lewis, Simon J G

    2018-03-12

    Freezing of gait is a devastating symptom of Parkinson's disease and other forms of parkinsonism. It poses a major burden on both patients and their families, as freezing often leads to falls, fall-related injuries and a loss of independence. Treating freezing of gait is difficult for a variety of reasons: it has a paroxysmal and unpredictable nature; a multifaceted pathophysiology, with an interplay between motor elements (disturbed stepping mechanisms) and non-motor elements (cognitive decline, anxiety); and a complex (and likely heterogeneous) underlying neural substrate, involving multiple failing neural networks. In recent years, advances in translational neuroscience have offered new insights into the pathophysiology underlying freezing. Furthermore, the mechanisms behind the effectiveness of available treatments (or lack thereof) are better understood. Driven by these concepts, researchers and clinicians have begun to improve currently available treatment options, and develop new and better treatment methods. Here, we evaluate the range of pharmacological (i.e. closed-looped approaches), surgical (i.e. multi-target and adaptive deep brain and spinal cord stimulation) and behavioural (i.e. biofeedback and cueing on demand) treatment options that are under development, and propose novel avenues that are likely to play a crucial role in the clinical management of freezing of gait in the near future. The outcomes of this review suggest that the successful future management of freezing of gait will require individualized treatments that can be implemented in an on-demand manner in response to imminent freezing. With this review we hope to guide much-needed advances in treating this devastating symptom of Parkinson's disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Long-term management of cirrhosis. Appropriate supportive care is both critical and difficult.

    PubMed

    Habib, A; Bond, W M; Heuman, D M

    2001-03-01

    Orthotopic liver transplantation has emerged as an important treatment option for patients with advanced liver disease. However, each year the number of new cases of cirrhosis exceeds the number of livers available for transplantation by a factor of 5 to 10. This translates into long waiting lists and restrictive criteria for selecting transplant recipients. Until advances in surgical technique or biotechnology increase the availability of organs for transplantation, the majority of patients with advanced liver disease will have to be managed medically for years--perhaps indefinitely. Early consultation with a liver transplant center can be helpful. The transplant hepatologist and surgeon can help with triage decisions, guide workup, provide advice about patient care, optimize the timing of transplantation, offer specialized diagnostic and therapeutic options, and help the treating physician stay abreast of the continuous changes in this complex field. In the final analysis, however, it is often the skill and diligence of the primary care physician in diagnosing liver disease, identifying and treating correctable causes, optimizing the patient's health and nutrition, and anticipating and preventing catastrophic complications that determine whether the patient lives or dies.

  9. Cost comparison of full-scale water reclamation technologies with an emphasis on membrane bioreactors.

    PubMed

    Iglesias, Raquel; Simón, Pedro; Moragas, Lucas; Arce, Augusto; Rodriguez-Roda, Ignasi

    2017-06-01

    The paper assesses the costs of full-scale membrane bioreactors (MBRs). Capital expenditures (CAPEX) and operating expenses (OPEX) of Spanish MBR facilities have been verified and compared to activated sludge plants (CAS) using water reclamation treatment (both conventional and advanced). Spanish MBR facilities require a production of 0.6 to 1.2 kWh per m 3 , while extended aeration (EA) and advanced reclamation treatment require 1.2 kWh per m 3 . The energy represents around 40% of the OPEX in MBRs. In terms of CAPEX, the implementation costs of a CAS facility followed by conventional water reclamation treatment (physical-chemical + sand filtration + disinfection) ranged from 730 to 850 €.m -3 d, and from 1,050 to 1,250 €.m -3 d in the case of advanced reclamation treatment facilities (membrane filtration) with a capacity of 8,000 to 15,000 m 3 d -1 . The MBR cost for similar capacities ranges between 700 and 960 €.m -3 d. This study shows that MBRs that have been recently installed represent a cost competitive option for water reuse applications for medium and large capacities (over 10,000 m 3 d -1 ), with similar OPEX to EA and conventional water reclamation treatment. In terms of CAPEX, MBRs are cheaper than EA, followed by advanced water reclamation treatment.

  10. Advances in Decoding Breast Cancer Brain Metastasis

    PubMed Central

    Zhang, Chenyu; Yu, Dihua

    2016-01-01

    The past decade has witnessed impressive advances in cancer treatment ushered in by targeted and immunotherapies. However, with significantly prolonged survival, upon recurrence, more patients become inflicted by brain metastasis, which is mostly refractory to all currently available therapeutic regimens. Historically, brain metastasis is an understudied area in cancer research, partly due to the dearth of appropriate experimental models that closely simulate the special biological features of metastasis in the unique brain environment; and to the sophistication of techniques required to perform in-depth studies of the extremely complex and challenging brain metastasis. Yet, with increasing clinical demand for more effective treatment options, brain metastasis research has rapidly advanced in recent years. The present review spotlights the recent major progresses in basic and translational studies of brain metastasis with focuses on new animal models, novel imaging technologies, omics “big data” resources, and some new and exciting biological insights on brain metastasis. PMID:27873078

  11. Covered stent graft for treatment of a pseudoaneurysm and carotid blowout syndrome

    PubMed Central

    Janjua, Nazli; Alkawi, Ammar; Georgiadis, Alexandros L.; Kirmani, Jawad F.; Qureshi, Adnan I.

    2008-01-01

    Background Carotid blowout syndrome with pseudoaneurysm, a rapidly progressive pathology, may present emergently with massive oral hemorrhage. Use of an endograft prosthesis offers a treatment strategy with salvation of the carotid artery. Case History: A 55 year old man with advanced squamous cell carcinoma of the head and neck presented with recurrent transoral hemorrhage, requiring endovascular treatment. Technical Report: Coil embolization was initially performed with little impact on the hemorrhage. A 7 x 40 mm Fluency® Plus covered stent (Bard Peripheral Vascular, Tempe, Arizona, USA) was placed and was supplemented by a second 8 x 40 mm Fluency Plus stent, with resulting cessation of active contrast extravasation. Discussion: The risks and benefits of various treatment options of carotid pseudoaneurysm with blowout are discussed including the use or omission of antiplatelet and anticoagulant regimens, with reference to previously reported cases. Conclusion: Tandem, overlapping covered stent placement in the common carotid artery is feasible and offers a treatment option for carotid blowout syndrome. Risks of aggravation of hemorrhage versus long-term thromboembolic events without antiplatelet therapy must be considered in cases of active ongoing hemorrhage. PMID:22518207

  12. Assessment of quality of life in patients with advanced non-small cell lung carcinoma treated with a combination of carboplatin and paclitaxel*

    PubMed Central

    Avelino, Camila Uanne Resende; Cardoso, Rafael Marques; de Aguiar, Suzana Sales; da Silva, Mário Jorge Sobreira

    2015-01-01

    OBJECTIVE: Non-small cell lung carcinoma (NSCLC) is the most common type of lung cancer. Most patients are diagnosed at an advanced stage, palliative chemotherapy therefore being the only treatment option. This study was aimed at evaluating the health-related quality of life (HRQoL) of advanced-stage NSCLC patients receiving palliative chemotherapy with carboplatin and paclitaxel. METHODS: This was a multiple case study of advanced-stage NSCLC outpatients receiving chemotherapy at a public hospital in Rio de Janeiro, Brazil. The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire was used in conjunction with its supplemental lung cancer-specific module in order to assess HRQoL. RESULTS: Physical and cognitive functioning scale scores differed significantly among chemotherapy cycles, indicating improved and worsened HRQoL, respectively. The differences regarding the scores for pain, loss of appetite, chest pain, and arm/shoulder pain indicated improved HRQoL. CONCLUSIONS: Chemotherapy was found to improve certain aspects of HRQoL in patients with advanced-stage NSCLC. PMID:25972967

  13. The Effect of Stabilization Treatments on Disk Alloy CH98

    NASA Technical Reports Server (NTRS)

    Gayda, John; Gabb, Timothy P.; Ellis, David L.

    2003-01-01

    Gas turbine engines for future subsonic transports will probably have higher pressure ratios which will require nickelbase superalloy disks with 1300 to 1400 F temperature capability. Several advanced disk alloys are being developed to fill this need. One of these, CH98, is a promising candidate for gas turbine engines and is being studied in NASA s Advanced Subsonic Technology (AST) program. For large disks, residual stresses generated during quenching from solution heat treatments are often reduced by a stabilization heat treatment, in which the disk is heated to 1500 or 1600 F for several hours followed by a static air cool. The reduction in residual stress levels lessens distortion during machining of disks. However, previous work on CH98 has indicated that stabilization treatments can also decrease creep capability. In this study, a systematic variation of stabilization temperature and time was investigated to determine its effect on 1300 F tensile and, more importantly, creep behavior. Dwell crack growth rates were also measured for selected stabilization conditions. As these advanced disk alloys may be given a supersolvus solution or a subsolvus solution heat treatment for a given application, it was decided that both options would be studied.

  14. The role and structure of the multidisciplinary team in the management of advanced Parkinson’s disease with a focus on the use of levodopa–carbidopa intestinal gel

    PubMed Central

    Pedersen, Stephen W; Suedmeyer, Martin; Liu, Louis W C; Domagk, Dirk; Forbes, Alison; Bergmann, Lars; Onuk, Koray; Yegin, Ashley; van Laar, Teus

    2017-01-01

    A multidisciplinary team (MDT) approach is increasingly recommended in Parkinson’s disease (PD) treatment guidelines, but no standard of care exists for such an approach, and the guidelines do not provide clarification on how it should be implemented. This paper reviews evidence of MDT interventions in people with PD and provides expert clinical perspectives for an MDT approach, with a focus on advanced PD and levodopa–carbidopa intestinal gel (carbidopa–levodopa enteral suspension in the USA). The key recommendations are to enable the best possible treatment of people with PD locally by facilitating a close structured collaboration of different health care professionals working in a fixed network structure; to refer people with PD to established MDT centers in a timely manner; to establish regular meetings for the MDT enabling interdisciplinary exchange and learning; to optimize individual treatment and carefully evaluate available treatment options; to ensure treatment decisions are agreed jointly between people with PD, their caregivers, family, and health care professional; and to include specialists outside of neurology from adjuvant medical departments as necessary when implementing advanced therapies. PMID:28115853

  15. Antisense Oligonucleotide Therapy for Patients with Advanced Cancer | Center for Cancer Research

    Cancer.gov

    Colorectal cancer (CRC) is the second leading cause of cancer-related death in the U.S. Improvements in therapy have increased the survival of patients with CRC from 10 months to two years, but for patients who stop responding to treatments, such as irinotecan, options for additional therapy are limited. Antisense oligonucleotides (ASOs) may offer advantages over traditional

  16. Thyroid cancer: what to do after fine needle aspiration.

    PubMed

    Rometo, David A; Baranski, Thomas J

    2011-01-01

    The incidence of differentiated thyroid cancer (including papillary, follicular, and Hurthle cell carcinoma) has nearly tripled in the past 20 years. Diagnosis, treatment, and long-term management are evolving with advances in radiology, surgical techniques, nuclear medicine, genetics, and targeted therapeutics. Here we detail the current recommended course of action for differentiated thyroid cancer and options on the horizon.

  17. Clinical aspects of palliative care in advanced Parkinson’s disease

    PubMed Central

    2012-01-01

    Parkinson's disease (PD) is one of the most common neurodegenerative disorders of the elderly population. Few therapeutic options are available for patients with PD requiring palliative care. Treatment of the early stages of PD is entirely different from later stages. During the later stages, the palliative care model is introduced to provide the patient with comfort and support. Early palliative care in PD requires minimization of dyskinesias and decreasing occurrence of motor and non-motor off times in an effort to maximize independent motor function. In the later stages, the focus of treatment shifts to treating the predominant non-motor symptoms and having a more supportive and palliative nature. The purpose of this review is to provide a summary of the palliative care management issues and palliative care management options of end-stage PD patients. PMID:23098090

  18. Surgical treatment of ulcerative colitis in the biologic therapy era

    PubMed Central

    Biondi, Alberto; Zoccali, Marco; Costa, Stefano; Troci, Albert; Contessini-Avesani, Ettore; Fichera, Alessandro

    2012-01-01

    Recently introduced in the treatment algorithms and guidelines for the treatment of ulcerative colitis, biological therapy is an effective treatment option for patients with an acute severe flare not responsive to conventional treatments and for patients with steroid dependent disease. The reduction in hospitalization and surgical intervention for patients affected by ulcerative colitis after the introduction of biologic treatment remains to be proven. Furthermore, these agents seem to be associated with increase in cost of treatment and risk for serious postoperative complications. Restorative proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of choice in ulcerative colitis patients. Surgery is traditionally recommended as salvage therapy when medical management fails, and, despite advances in medical therapy, colectomy rates remain unchanged between 20% and 30%. To overcome the reported increase in postoperative complications in patients on biologic therapies, several surgical strategies have been developed to maintain long-term pouch failure rate around 10%, as previously reported. Surgical staging along with the development of minimally invasive surgery are among the most promising advances in this field. PMID:22563165

  19. A comprehensive review and update on the biologic treatment of adult noninfectious uveitis: part II.

    PubMed

    Lee, Kyungmin; Bajwa, Asima; Freitas-Neto, Clovis A; Metzinger, Jamie Lynne; Wentworth, Bailey A; Foster, C Stephen

    2014-11-01

    Treatment of adult, noninfectious uveitis remains a major challenge for ophthalmologists around the world, especially in regard to recalcitrant cases. It is reported to comprise approximately 10% of preventable blindness in the USA. The cause of uveitis can be idiopathic or associated with infectious and systemic disorders. The era of biologic medical therapies provides new options for patients with otherwise treatment-resistant inflammatory eye disease. This two-part review gives a comprehensive overview of the existing medical treatment options for patients with adult, noninfectious uveitis, as well as important advances for the treatment ocular inflammation. Part I covers classic immunomodulation and latest information on corticosteroid therapy. In part II, emerging therapies are discussed, including biologic response modifiers, experimental treatments and ongoing clinical studies for uveitis. The hazard of chronic corticosteroid use in the treatment of adult, noninfectious uveitis is well documented. Corticosteroid-sparing therapies, which offer a very favorable risk-benefit profile when administered properly, should be substituted. Although nothing is currently approved for on-label use in this indication, many therapies, through either translation or novel basic science research, have the potential to fill the currently exposed gaps.

  20. New agents for the management of resistant metastatic breast cancer.

    PubMed

    Anampa, Jesus; Sparano, Joseph A

    2017-12-01

    Metastatic breast cancer (MBC) is an incurable disease and treatment is directed towards symptom palliation and survival prolongation. Treatment selection in patients is based on tumor biology, age, comorbidities, performance status, tumor burden, and prior treatment history. Areas covered: This present review summarizes the recent treatment strategies in the management of MBC, highlighting regimens after first-line therapy. Topics discussed include new strategies for endocrine therapy, anti-HER2 therapy, and promising strategies for the management of triple negative breast cancer. Expert opinion: MBC is a heterogeneous entity and despite recent advances, there is significant room for improvement of treatment beyond first-line therapies. Combination regimens that can maximize clinical efficacy while minimizing toxicities are required. Current investigation approaches in advanced stages of clinical development include immunoconjugates, immune checkpoint blockade, novel cyclin-dependent-kinase inhibitors, and PARP inhibitors for MBC associated with germline BRCA mutations. We recommend that every patient with MBC should be evaluated for clinical trial options.

  1. Evolution of checkpoint inhibitors for the treatment of metastatic gastric cancers: Current status and future perspectives.

    PubMed

    Taieb, Julien; Moehler, Markus; Boku, Narikazu; Ajani, Jaffer A; Yañez Ruiz, Eduardo; Ryu, Min-Hee; Guenther, Silke; Chand, Vikram; Bang, Yung-Jue

    2018-05-01

    Standard treatment options for patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC) are associated with limited efficacy and some toxicity. Recently, immunotherapy with antibodies that inhibit the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) interaction has emerged as a new treatment option. This manuscript reviews early-phase and late-phase trials of immunotherapy in advanced GC/GEJC. Searches for studies of immunotherapy in GC/GEJC were performed using PubMed, ClinicalTrials.gov, and abstract databases for select annual congresses. Findings were interpreted based on expert opinion. Monotherapy with anti-PD-1/PD-L1 antibodies, including pembrolizumab, nivolumab, avelumab, durvalumab, and atezolizumab, has shown interesting objective response rates (ORRs; 7-26%) across varying GC/GEJC populations, with ORRs potentially higher in PD-L1 + vs PD-L1 - tumors. Safety profiles compare favorably with chemotherapy, with grade ≥3 treatment-related adverse events occurring in 5-17%. Based on a large phase 2 study, pembrolizumab was approved in the United States for third-line treatment of patients with PD-L1 + GC/GEJC. In a phase 3 trial, third-line or later nivolumab increased overall survival vs placebo in an Asian population, leading to regulatory approval in Japan, although other completed phase 3 trials did not show superiority for pembrolizumab or avelumab monotherapy vs chemotherapy. Other trials in advanced GC/GEJC are assessing various anti-PD-1/PD-L1-based strategies, including administration in first-line and later-line settings and as combination (with chemotherapy or agents targeting other immune checkpoint proteins, eg, CTLA-4, LAG-3, and IDO) or switch-maintenance regimens. Anti-PD-1/PD-L1 antibodies have shown encouraging clinical activity in advanced GC/GEJC. Results from ongoing phase 3 trials are needed to further evaluate the potential roles of these agents within the continuum of care. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. [Rescue cryotherapy for prostate cancer after radiotherapy].

    PubMed

    García, Erique Lledó; Amo, Felipe Herranz; San Segundo, Carmen González; Fagundo, Eva Paños; Escudero, Roberto Molina; Alonso, Adrian Husillos; Piniés, Gabriel Ogaya; Rascón, Jose Jara; Fernández, Carlos Hernández

    2012-01-01

    Radical Radiotherapy constitutes a useful therapeutic option for localized prostate cancer. Almost one third of prostate cancer patients choose this alternative to treat the disease. Despite modifications in the technique as intensity modulation, 3D conformational radiotherapy or computer-assisted brachytherapy, a significant percentage of these patients will show an increase in PSA values after radiation. Local relapse without distant disease and PSA less than 10 ng/ml are candidates for salvage therapy. Cryotherapy has already become a curative treatment option in this group of patients. Recent technological as well as surgical advances in salvage-cryotherapy have reduced dramatically complications and progressively increase the interest on this alternative.

  3. Constipation-predominant irritable bowel syndrome: A review of current and emerging drug therapies

    PubMed Central

    Jadallah, Khaled A; Kullab, Susan M; Sanders, David S

    2014-01-01

    Irritable bowel syndrome (IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS (IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators. PMID:25083062

  4. New developments in the management of neurogenic orthostatic hypotension.

    PubMed

    Biaggioni, Italo

    2014-11-01

    Orthostatic hypotension (OH) is defined as a sustained reduction of ≥ 20 mmHg systolic blood pressure or ≥ 10 mmHg diastolic blood pressure upon standing for ≤ 3 min. Orthostatic hypotension is commonly associated with hypertension, and its prevalence is highest in those with uncontrolled hypertension compared to those with controlled hypertension or normotensive community elderly subjects. Orthostatic hypotension can cause significant disability, with patients experiencing dizziness, lightheadedness or syncope, and other problems that potentially have a profound negative impact on activities of daily living that require standing or walking. Furthermore, OH increases the risk of falls and, importantly, is an independent risk factor of mortality. Despite its importance, there is a paucity of treatment options for this condition. Most of the advances in treatment options have relied on small studies of repurposed drugs done in patients with severe OH due to rare neurodegenerative conditions. Midodrine, an oral prodrug converted to the selective α1-adrenoceptor agonist desglymidodrine, was approved by the FDA for the treatment of OH in 1996. For almost two decades, no other pharmacotherapy was developed specifically for the treatment of OH until 2014, when droxidopa was approved by the FDA for the treatment of neurogenic OH associated with primary autonomic neuropathies including Parkinson disease, multiple system atrophy, and pure autonomic failure. These are neurodegenerative diseases ultimately characterized by failure of the autonomic nervous system to generate norepinephrine responses appropriate to postural challenge. Droxidopa is a synthetic amino acid that is converted to norepinephrine by dopa-decarboxylase, the same enzyme that converts levodopa into dopamine in the treatment of Parkinson disease. We will review this and other advances in the treatment of OH in an attempt to provide a practical guide to its management.

  5. Patient-family agreement on values and preferences for life-sustaining treatment: results of a multicentre observational study.

    PubMed

    Abdul-Razzak, Amane; Heyland, Daren K; Simon, Jessica; Ghosh, Sunita; Day, Andrew G; You, John J

    2017-07-22

    To quantify agreement between patients and their family members on their own values and preferences for use or non-use of life-sustaining treatments for the patient. Hospitalised patients aged 55 years or older with advanced pulmonary, cardiac, liver disease or metastatic cancer or aged 80 years or older from medical wards at 16 Canadian hospitals and their family members completed a questionnaire including eight items about values related to life-sustaining treatment and a question about preferences for life-sustaining treatments. We recruited a total of 313 patient-family member dyads. Crude agreement between patients and family members about values related to life-sustaining treatment was 42% across all eight items but varied widely: 20% when asking how important it was for the patient to respect the wishes of family members regarding their care; 72% when asking how important it was for the patient to be kept comfortable and suffer as little as possible. Crude agreement on preferences for life-sustaining treatment was 91% (kappa 0.60; 95%CI 0.45 to 0.75) when looking at preferences for cardiopulmonary resuscitation (CPR) versus no CPR but fell to 56% when including all five response options with varying degrees of resuscitative, medical or comfort options (kappa 0.39; 95%CI 0.31 to 0.47). There is appreciable disagreement between seriously ill hospitalised patients and family members in their values and preferences for life-sustaining treatment. Strategies are needed to improve the quality of advance care planning, so that surrogates are better able to honour patient's wishes at the end of life. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. Adrenal Surgery for Cushing's Syndrome: An Update.

    PubMed

    Di Dalmazi, Guido; Reincke, Martin

    2018-06-01

    Recent advances in the molecular pathogenesis and the natural history of Cushing's syndrome have improved the understanding of the management of this disease. The long-term efficacy of several cortisol-lowering medical treatments is currently under evaluation. However, adrenalectomy is a safe option for the treatment of patients affected by Cushing's syndrome. Unilateral adrenalectomy is the gold standard for treatment of adrenocortical adenomas associated with hypercortisolism. Bilateral adrenalectomy has been widely used in the past as definitive treatment of bilateral macronodular hyperplasia and persistent or recurrent Cushing's disease. The indication and the potential applications of this technique have been recently critically analyzed. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. [Abscess at the implant site following apical parodontitis. Hardware-related complications of deep brain stimulation].

    PubMed

    Sixel-Döring, F; Trenkwalder, C; Kappus, C; Hellwig, D

    2006-08-01

    Deep brain stimulation of the subthalamic nucleus is an important treatment option for advanced stages of idiopathic Parkinson's disease, leading to significant improvement of motor symptoms in suited patients. Hardware-related complications such as technical malfunction, skin erosion, and infections however cause patient discomfort and additional expense. The patient presented here suffered a putrid infection of the impulse generator site following only local dental treatment of apical parodontitis. Therefore, prophylactic systemic antibiotic treatment is recommended for patients with implanted deep brain stimulation devices in case of operations, dental procedures, or infectious disease.

  8. Targeted therapies in gastric cancer and future perspectives.

    PubMed

    Yazici, Ozan; Sendur, M Ali Nahit; Ozdemir, Nuriye; Aksoy, Sercan

    2016-01-14

    Advanced gastric cancer (AGC) is associated with a high mortality rate and, despite multiple new chemotherapy options, the survival rates of patients with AGC remains poor. After the discovery of targeted therapies, research has focused on the new treatment options for AGC. In the last two decades, many targeted molecules were developed against AGC. Currently, two targeted therapy molecules have been approved for patients with AGC. In 2010, trastuzumab was the first molecule shown to improve survival in patients with HER2-positive AGC as part of a first-line combination regimen. In 2014, ramucirumab was the second targeted molecule to improve survival rates and was suggested as treatment for patients with AGC who had progressed after first-line platinum plus fluoropyrimidine with or without anthracycline chemotherapy. Ramucirumab was the first targeted therapy acting as a single agent in patients with advanced gastroesophageal cancers. Although these two molecules were introduced into clinical use, many other promising molecules have been tested in phase I-II trials. It is obvious that in the near future many different targeted therapies will be in use for treatment of AGC. In this review, the current status of targeted therapies in the treatment of AGC and gastroesophageal junction tumors, including HER (2-3) inhibitors, epidermal growth factor receptor inhibitors, tyrosine kinase inhibitors, antiangiogenic agents, c-MET inhibitors, mammalian target of rapamycin inhibitors, agents against other molecular pathways fibroblast growth factor, Claudins, insulin-like growth factor, heat shock proteins, and immunotherapy, will be discussed.

  9. Cost-effectiveness of gefitinib, icotinib, and pemetrexed-based chemotherapy as first-line treatments for advanced non-small cell lung cancer in China

    PubMed Central

    Lu, Shun; Ye, Ming; Ding, Lieming; Tan, Fenlai; Fu, Jie; Wu, Bin

    2017-01-01

    Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR) are becoming the standard treatment option for patients with advanced non-small cell lung cancer (NSCLC) harboring an EGFR mutation, but the economic impact of this practice is unclear, especially in a health resource-limited setting. A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The health and economic outcomes of four first-line strategies (pemetrexed plus cisplatin [PC] alone, PC followed by maintenance with pemetrexed, or initial treatment with gefitinib or icotinib) among patients harboring EGFR mutations were estimated and assessed via indirect comparisons. Costs in the Chinese setting were estimated. The primary outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed. The icotinib strategy resulted in greater health benefits than the other three strategies in NSCLC patients harboring EGFR mutations. Relative to PC alone, PC followed by pemetrexed maintenance, gefitinib and icotinib resulted in ICERs of $104,657, $28,485 and $19,809 per quality-adjusted life-year gained, respectively. The cost of pemetrexed, the EGFR mutation prevalence and the utility of progression-free survival were factors that had a considerable impact on the model outcomes. When the icotinib Patient Assistance Program was available, the economic outcome of icotinib was more favorable. These results indicate that gene-guided therapy with icotinib might be a more cost-effective treatment option than traditional chemotherapy. PMID:28036283

  10. Cost-effectiveness of gefitinib, icotinib, and pemetrexed-based chemotherapy as first-line treatments for advanced non-small cell lung cancer in China.

    PubMed

    Lu, Shun; Ye, Ming; Ding, Lieming; Tan, Fenlai; Fu, Jie; Wu, Bin

    2017-02-07

    Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR) are becoming the standard treatment option for patients with advanced non-small cell lung cancer (NSCLC) harboring an EGFR mutation, but the economic impact of this practice is unclear, especially in a health resource-limited setting. A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The health and economic outcomes of four first-line strategies (pemetrexed plus cisplatin [PC] alone, PC followed by maintenance with pemetrexed, or initial treatment with gefitinib or icotinib) among patients harboring EGFR mutations were estimated and assessed via indirect comparisons. Costs in the Chinese setting were estimated. The primary outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed. The icotinib strategy resulted in greater health benefits than the other three strategies in NSCLC patients harboring EGFR mutations. Relative to PC alone, PC followed by pemetrexed maintenance, gefitinib and icotinib resulted in ICERs of $104,657, $28,485 and $19,809 per quality-adjusted life-year gained, respectively. The cost of pemetrexed, the EGFR mutation prevalence and the utility of progression-free survival were factors that had a considerable impact on the model outcomes. When the icotinib Patient Assistance Program was available, the economic outcome of icotinib was more favorable. These results indicate that gene-guided therapy with icotinib might be a more cost-effective treatment option than traditional chemotherapy.

  11. Development and evaluation of an aged care specific Advance Care Plan.

    PubMed

    Silvester, William; Parslow, Ruth A; Lewis, Virginia J; Fullam, Rachael S; Sjanta, Rebekah; Jackson, Lynne; White, Vanessa; Hudson, Rosalie

    2013-06-01

    To report on the quality of advance care planning (ACP) documents in use in residential aged care facilities (RACF) in areas of Victoria Australia prior to a systematic intervention; to report on the development and performance of an aged care specific Advance Care Plan template used during the intervention. An audit of the quality of pre-existing documentation used to record resident treatment preferences and end-of-life wishes at participating RACFs; development and pilot of an aged care specific Advance Care Plan template; an audit of the completeness and quality of Advance Care Plans completed on the new template during a systematic ACP intervention. 19 selected RACFs (managed by 12 aged care organisations) in metropolitan and regional areas of Victoria. Documentation in use at facilities prior to the ACP intervention most commonly recorded preferences regarding hospital transfer, life prolonging treatment and personal/cultural/religious wishes. However, 7 of 12 document sets failed to adequately and clearly specify the resident's preferences as regards life prolonging medical treatment. The newly developed aged care specific Advance Care Plan template was met with approval by participating RACFs. Of 203 Advance Care Plans completed on the template throughout the project period, 49% included the appointment of a Medical Enduring Power of Attorney. Requests concerning medical treatment were specified in almost all completed documents (97%), with 73% nominating the option of refusal of life-prolonging treatment. Over 90% of plans included information concerning residents' values and beliefs, and future health situations that the resident would find to be unacceptable were specified in 78% of completed plans. Standardised procedures and documentation are needed to improve the quality of processes, documents and outcomes of ACP in the residential aged care sector.

  12. Optimal prophylactic and definitive therapy for bicalutamide-induced gynecomastia: results of a meta-analysis

    PubMed Central

    Tunio, M.A.; Al-Asiri, M.; Al-Amro, A.; Bayoumi, Y.; Fareed, M.

    2012-01-01

    Objective Bicalutamide is approved as an adjuvant to primary treatments (radical prostatectomy or radiotherapy) or as monotherapy in men with locally advanced, nonmetastatic prostate cancer (pca). However, this treatment induces gynecomastia in most patients, which often results in treatment discontinuation. Optimal therapy for these breast events is not known so far. We undertook a meta-analysis to assess the efficacy of various treatment options for bicalutamide-induced gynecomastia. Methods The medline, cancerlit, and Cochrane library databases were searched and the Google search engine was used to identify prospective and retrospective controlled studies published in English from January 2000 to December 2010 comparing prophylactic or curative treatment options with a control group (no treatment) for pca patients who developed bicalutamide-induced gynecomastia. Radiotherapy-induced cardiotoxicity was also evaluated. Results The search identified nine controlled trials with a total patient population of 1573. Pooled results from prophylactic trials showed a significant reduction of gynecomastia in pca patients treated with prophylactic tamoxifen 20 mg daily (odds ratio: 0.06; 95% confidence interval: 0.05 to 0.09; p = 0.09), and pooled results from treatment trials showed a significant response of gynecomastia to definitive radiotherapy (odds ratio: 0.06; 95% confidence interval: 0.01 to 0.24; p < 0.0001). Aromatase inhibitors and weekly tamoxifen were not found to be effective as prophylactic and curative options. For the radiotherapy, skin-to-heart distance was found to be an important risk factor for cardiotoxicity (p = 0.006). A funnel plot of the meta-analysis showed significant heterogeneity (Egger test p < 0.00001) because of low sample size. Conclusions Our meta-analysis suggests using prophylactic tamoxifen 20 mg daily as the first-line preventive measure and radiotherapy as the first-line treatment option for bicalutamide-induced gynecomastia. Aromatase inhibitors and weekly tamoxifen are not recommended. PMID:22876157

  13. Treatment of advanced refractory sarcomas with ifosfamide and etoposide combination chemotherapy.

    PubMed

    Yalçin, S; Güllü, I; Barişta, I; Tekuzman, G; Ozişik, Y; Celik, I; Kars, A

    1998-01-01

    Chemotherapy options for resistant advanced-stage sarcomas are limited and in most cases disappointing. In a phase II study, we treated 26 consecutive patients with refractory advanced sarcoma with ifosfamide and etoposide combination chemotherapy. All patients had received prior doxorubicin- and/or cyclophosphamide-based chemotherapies. Seventeen patients were male and 9 were female. The patients' median age was 35 years (range: 19-67 years). A total of 24 patients were eligible for evaluation of responses. Seven patients had a complete response (CR) (29.1%), 3 had a partial response (PR) (12.5%), 3 had stable disease (SD) (12.5%), and 11 had progressive disease (PD) (45.9%). An overall 41.6% objective response was achieved. Median time to treatment failure was 13.3 months. A total of 108 cycles of therapy were evaluable for evaluation of toxicity. Myelosuppression, observed in 55.5% of the treatment courses, was the major dose-limiting toxicity. Nausea and vomiting, seen in 64% of the courses, were the most important nonhematological side effects. Alopecia was almost universal. Hemorrhagic cystitis was observed in only 1 patient. We have concluded that the combination of ifosfamide, mesna, and etoposide is effective in advanced refractory sarcomas, and has acceptable toxicity.

  14. Advances of Molecular Targeted Therapy in Gastric Cancer.

    PubMed

    Cetin, Bulent; Gumusay, Ozge; Cengiz, Mustafa; Ozet, Ahmet

    2016-06-01

    Gastric cancer is the second most common cause of cancer-related death in the world, and its prognosis remains poor with a median overall survival of 12 months for advanced disease. Advances in the understanding of molecular genetics have led to the development of directed molecular targeted therapy in gastric cancer, leading to improve patient outcomes and quality of life. In the treatment of human epidermal growth factor receptor 2 (HER2)-positive gastric cancer, the addition of trastuzumab significantly improves survival in the first-line setting of therapy. Ramucirumab, an antibody directed against vascular endothelial growth factor receptor 2, significantly improved progression-free and overall survival and has been approved for second-line treatment of gastric cancer. Anti-mesenchymal-epithelial transition (c-MET), mammalian target of rapamycin inhibitors, and polo-like kinase 1 inhibitors are under investigation as a novel therapeutic option for the treatment of gastric cancer. The novel therapies target the key immune checkpoint interaction between a T cell co-inhibitory receptor called programmed death 1 (PD-1) and one of its immunosuppressive ligands, PD-L1. This article reviews molecular targeted therapies in gastric cancer, in light of recent advances.

  15. Fixed-dose-rate gemcitabine: a viable first-line treatment option for advanced pancreatic and biliary tract cancer.

    PubMed

    Milella, Michele; Gelibter, Alain J; Pino, Maria Simona; Bossone, Giandominik; Marolla, Paolo; Sperduti, Isabella; Cognetti, Francesco

    2010-01-01

    We have already reported on fixed-dose-rate gemcitabine (FDR-Gem) in advanced, inoperable pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancer (BTC) in the context of a formal phase II study; building on that experience, we have now expanded the study to reach a cumulative accrual of 106 patients. One hundred six patients (PDAC/BTC, 75/31) were treated with weekly FDR-Gem (1,000 mg/m(2) infused at 10 mg/m(2) per minute). Patient characteristics included: male-to-female ratio, 0.83; median age, 63 years (range, 28-82); metastatic disease in 66% of patients; and an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-1 in 81% of patients. The median and total number of treatment weeks delivered were 8 (range, 2-22) and 1,154, respectively. Thirteen percent of patients achieved an objective response, 42% experienced a positive clinical benefit response, and 54% achieved a >50% reduction in serum cancer antigen (CA)19.9 levels. The median progression-free survival (PFS) and overall survival (OS) times for the entire population were 4.4 months (95% confidence interval [CI], 3.5-5.1 months) and 7.7 months (95% CI, 6.3-8.8 months), respectively, with 20% of patients alive at 1 year. On multivariate analysis, a CA19.9 reduction >50% and baseline ECOG PS score of 0 were the only independent predictors of PFS and OS, respectively. Treatment was well tolerated, with grade 3-4 neutropenia in 47 of 1,154 treatment weeks (4.1%), and grade 3 anemia and thrombocytopenia in 8 of 1,154 (0.7%) and 16 of 1,154 (1.4%) treatment weeks, respectively. Currently available evidence, including this updated analysis, supports the use of FDR-Gem as a first-line option in advanced PDAC, and possibly in BTC, patients and prompts the continued evaluation of this approach in combination regimens.

  16. A Review of Pharmacological Treatment Options for Lung Cancer: Emphasis on Novel Nanotherapeutics and Associated Toxicity.

    PubMed

    England, Christopher G; Ng, Chin F; van Berkel, Victor; Frieboes, Hermann B

    2015-01-01

    Lung cancer remains a leading cause of death. Current treatment options are generally ineffective, highlighting the dire need for novel approaches. While numerous biologically-active chemotherapeutics have been discovered in the last two decades, biological barriers including minimal water solubility, stability, and cellular resistance hinder in vivo effectiveness. To overcome these limitations, nanoparticles have been designed to deliver chemotherapeutics selectively to cancerous tissue while minimizing pharmacokinetics hindrance. Numerous studies are underway analyzing the efficacy of nanoparticles in drug delivery, theranostic applications, and photothermal therapy. However, while nanoparticles have shown efficacy in treating some cancers, their potential toxicity and lack of targeting may hinder clinical potential. With the aim to help sort through these issues, we conduct a review to describe recent applications of nanotherapeutics for the treatment and diagnosis of lung cancer. We first provide a detailed background of statistics, etiology, histological classification, staging, diagnosis, and current treatment options. This is followed by a description of current applications of nanotherapeutics, focusing primarily on results published during the past five years. The potential toxicity associated with nanoparticles is evaluated, revealing inconclusive information which highlights the need for further studies. Lastly, recent advances in mathematical modeling and computational simulation have shown potential in predicting tumor response to nanotherapeutics. Thus, although nanoparticles have shown promise in treating lung cancer, further multi-disciplinary studies to quantify optimal dosages and assess possible toxicity are still needed. To this end, nanotherapeutic options currently in clinical trials offer hope to help address some of these critical issues.

  17. An Update on Modern Approaches to Localized Esophageal Cancer

    PubMed Central

    Welsh, James; Amini, Arya; Likhacheva, Anna; Erasmus, Jeremy; Gomez, Daniel; Davila, Marta; Mehran, Reza J; Komaki, Ritsuko; Liao, Zhongxing; Hofstetter, Wayne L; Bhutani, Manoop; Ajani, Jaffer A

    2014-01-01

    Esophageal cancer treatment continues to be a topic of wide debate. Based on improvements in chemotherapy drugs, surgical techniques, and radiotherapy advances, esophageal cancer treatment approaches are becoming more specific to the stage of the tumor and the overall performance status of the patient. While surgery continues to be the standard treatment option for localized disease, the current direction favors multimodality treatment including both radiation and chemotherapy with surgery. In the next few years, we will continue to see improvements in radiation techniques and proton treatment, with more minimally invasive surgical approaches minimizing postoperative side effects, and the discovery of molecular biomarkers to help deliver more specifically targeted medication to treat esophageal cancers. PMID:21365188

  18. Cost-effectiveness analysis of apatinib treatment for chemotherapy-refractory advanced gastric cancer.

    PubMed

    Chen, Hong-Dou; Zhou, Jing; Wen, Feng; Zhang, Peng-Fei; Zhou, Ke-Xun; Zheng, Han-Rui; Yang, Yu; Li, Qiu

    2017-02-01

    Apatinib, a third-line or later treatment for advanced gastric cancer (aGC), was shown to improve overall survival and progression-free survival (PFS) compared with placebo in the phase III trial. Given the modest benefit with high costs, we further evaluated the cost-effectiveness of apatinib for patients with chemotherapy-refractory aGC. A Markov model was developed to simulate the disease process of aGC (PFS, progressive disease, and death) and estimate the incremental cost-effectiveness ratio (ICER) of apatinib to placebo. The health outcomes and utility scores were derived from the phase III trial and previously published sources, respectively. Total costs were calculated from the perspective of the Chinese health-care payer. Sensitivity analysis was used to explore model uncertainties. Treatment with apatinib was estimated to provide an incremental 0.09 quality-adjusted life years (QALYs) at an incremental cost of $8113.86 compared with placebo, which resulted in an ICER of $90,154.00 per QALY. Sensitivity analysis showed that across the wide variation of parameters, the ICER exceeded the willingness-to-pay threshold of $23,700.00 per QALY which was three times the Gross Domestic Product per Capita in China. Apatinib is not a cost-effective option for patients with aGC who experienced failure of at least two lines chemotherapy in China. However, for its positive clinical value and subliminal demand, apatinib can provide a new therapeutic option.

  19. New innovations: therapeutic opportunities for intellectual disabilities.

    PubMed

    Picker, Jonathan D; Walsh, Christopher A

    2013-09-01

    Intellectual disability is common and is associated with significant morbidity. Until the latter half of the 20th century, there were no efficacious treatments. Following initial breakthroughs associated with newborn screening and metabolic corrections, little progress was made until recently. With improved understanding of genetic and cellular mechanisms, novel treatment options are beginning to appear for a number of specific conditions. Fragile X and tuberous sclerosis offer paradigms for the development of targeted therapeutics, but advances in understanding of other disorders such as Down syndrome and Rett syndrome, for example, are also resulting in promising treatment directions. In addition, better understanding of the underlying neurobiology is leading to novel developments in enzyme replacement for storage disorders and adjunctive therapies for metabolic disorders, as well as potentially more generalizable approaches that target dysfunctional cell regulation via RNA and chromatin. Physiologic therapies, including deep brain stimulation and transcranial magnetic stimulation, offer yet another direction to enhance cognitive functioning. Current options and evolving opportunities for the intellectually disabled are reviewed and exemplified. Copyright © 2013 American Neurological Association.

  20. Platelet-rich plasma and plantar fasciitis.

    PubMed

    Monto, Raymond R

    2013-12-01

    Plantar fasciitis is the most common cause of heel pain and can prove difficult to treat in its most chronic and severe forms. Advanced cases of plantar fasciitis are often associated with ankle stiffness, heel spurs, and other conditions and can lead to extensive physical disability and financial loss. Most available traditional treatments, including orthoses, nonsteroidal anti-inflammatory drugs, and steroid injections have a paucity of supportive clinical evidence. More invasive treatments, ranging from corticosteroid and botulinum-A toxin injections to shockwave therapy and plantar fasciotomy, have demonstrated varying clinical success in severe cases but carry the potential for serious complication and permanent disability. Platelet-rich plasma has recently been demonstrated to be helpful in managing chronic severe tendinopathies when other techniques have failed. This review examines the pathophysiology, diagnostic options, nonoperative treatment modalities, and surgical options currently used for plantar fasciitis. It also focuses on the clinical rationale and available evidence for using autologous platelet-rich plasma to treat severe refractory chronic plantar fasciitis.

  1. Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma

    PubMed Central

    Trojan, Jörg; Waidmann, Oliver

    2016-01-01

    Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC. PMID:27703962

  2. Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma.

    PubMed

    Trojan, Jörg; Waidmann, Oliver

    2016-01-01

    Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC.

  3. Myasthenia gravis: recent advances in immunopathology and therapy.

    PubMed

    Lee, John-Ih; Jander, Sebastian

    2017-03-01

    Myasthenia gravis is the most frequent acquired disorder of neuromuscular transmission. In the majority of cases, pathogenic antibodies against components of the postsynaptic muscle endplate membrane can be detected. In recent years there have been significant advances in the pathophysiological understanding and therapy of the disease. Areas covered: PubMed searches were conducted for the term 'myasthenia gravis' cross-referenced with the terms 'immunology', 'subgroups', 'antibody', 'ocular', 'thymoma', 'treatment' and 'thymectomy'. Additionally, we summarized the current state of immunopathology and therapy. Expert commentary: Immunological research defined new target antigens at the postsynaptic neuromuscular junction which along with clinical features allow a refined definition of disease subgroups. Overall the prognosis of myasthenia gravis with best possible symptomatic, immunosuppressive and supportive treatment is good but new immunomodulatory treatment options are developed for patients who do not respond well to the first line therapy. For most patients individually adapted long-term drug therapy is needed.

  4. Open Versus Endovascular or Hybrid Thoracic Aortic Aneurysm Repair.

    PubMed

    Clare, Ryan; Jorgensen, Julianne; Brar, Somjot S

    2016-10-01

    Thoracic aortic aneurysms are associated with significant morbidity and mortality. There are multiple underlying etiologies, including genetic abnormalities, that have important implications in their natural history. The variable histologic, anatomic, and clinical presentations necessitate careful consideration of available treatment options. Surgical repair of these aneurysms has been the mainstay of treatment; however, these approaches can carry a relatively high risk of morbidity and mortality. Endovascular approaches have now become first-line therapy for descending thoracic aneurysms, and with advancements in graft technology, endovascular approaches are being increasingly employed for hybrid repairs of the aortic arch and even the ascending aorta. However, to date, clinical outcomes from randomized trials and long-term follow-up are limited. As technology continues to advance, there is the potential for further integration of surgical and endovascular treatments so that patients have the best opportunity for a favorable outcome.

  5. New treatment options for metastatic renal cell carcinoma with prior anti-angiogenesis therapy.

    PubMed

    Zarrabi, Kevin; Fang, Chunhui; Wu, Shenhong

    2017-02-02

    Angiogenesis is a critical process in the progression of advanced renal cell carcinoma. Agents targeting angiogenesis have played a primary role in the treatment of metastatic renal cell carcinoma. However, resistance to anti-angiogenesis therapy almost always occurs, and major progress has been made in understanding its underlying molecular mechanism. Axitinib and everolimus have been used extensively in patients whom have had disease progression after prior anti-angiogenesis therapy. Recently, several new agents have been shown to improve overall survival in comparison with everolimus. This review provides an in-depth summary of drugs employable in the clinical setting, the rationale to their use, and the studies conducted leading to their approval for use and provides perspective on the paradigm shift in the treatment of renal cell carcinoma. Highlighted are the newly approved agents cabozantinib, nivolumab, and lenvatinib for advanced renal cell carcinoma patients treated with prior anti-angiogenesis therapy.

  6. Recent advance in immunological tests in paraneoplastic neurological syndrome.

    PubMed

    Fong, Chin-Shih

    2005-03-01

    Paraneoplastic neurological syndromes are uncommon, however; their diagnosis is of major practical importance. Any portion of the nervous system may be involved in paraneoplastic syndromes. There is increasing evidence that the pathogenesis of many paraneoplastic neurological syndromes appears to be an immune reaction against antigen shared by the cancer and the nervous system. The identification of antibodies in the serum or cerebrospinal fluid in the central nervous system of paraneoplastic syndrome patient confirms the clinical diagnosis of paraneoplastic syndrome, and allows early identification of an underlying tumor at a stage when it is localized and more amenable to treatment. Cancer therapy (surgery, radiotherapy, chemotherapy) seems to be the most efficient treatment for the paraneoplastic neurological symptoms. Immunomodulatory therapy (intravenous immunoglobulin, plasmapheresis, immunosuppression) can halt or even reverse the neurological syndrome. The recent advances in understanding of the autoimmune pathology of these disorders should lead to more effective treatment options.

  7. 78 FR 30948 - Self-Regulatory Organizations; Fixed Income Clearing Corporation; Notice of Filing of Advance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-23

    ... Options on Interest Rate Futures Contracts With Maturities Not Longer Than Two Years in the One- Pot Cross... allow FICC to include options on interest rate futures contracts with maturities not longer than two...) The purpose of the advance notice is to include options on interest rate futures contracts with...

  8. Patient and Oncology Nurse Preferences for the Treatment Options in Advanced Melanoma: A Discrete Choice Experiment.

    PubMed

    Liu, Frank Xiaoqing; Witt, Edward A; Ebbinghaus, Scot; DiBonaventura Beyer, Grace; Basurto, Enrique; Joseph, Richard W

    2017-10-25

    Understanding the perceptions of patients and oncology nurses about the relative importance of benefits and risks associated with newer treatments of advanced melanoma can help to inform clinical decision-making. The aims of this study were to quantify and compare the views of patients and oncology nurses regarding the importance of attributes of treatments of advanced melanoma. A discrete choice experiment (DCE) was conducted in US-based oncology nurses and patients diagnosed with advanced melanoma. Patients and nurses were enlisted through online panels. In a series of scenarios, respondents had to choose between 2 hypothetical treatments, each with 7 attributes: mode of administration (MoA), dosing schedule (DS), median duration of therapy (DoT), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and grade 3 or 4 adverse events (AEs). Hierarchical Bayesian logistic regression models were used to estimate preference weights. A total of 200 patients with advanced melanoma and 150 oncology nurses participated. The relative importance estimates of attributes by patients and nurses, respectively, were as follows: OS, 33% and 28%; AEs, 29% and 26%; ORR, 25% and 27%; PFS, 12% and 15%; DS, 2% and 3%; DoT, 0% and 0%; and MoA, 0% and 0%. Both patients and oncology nurses valued OS, ORR, and AEs as the most important treatment attributes for advanced melanoma, followed by PFS, whereas DS, DoT, and MoA were given less value in their treatment decisions. Oncology nurses and patients have similar views on important treatment considerations for advanced melanoma, which can help build trust in shared decision-making.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  9. Treatment Options to Manage Wound Biofilm

    PubMed Central

    Jones, Curtis E.; Kennedy, John P.

    2012-01-01

    Background Bioburden is an accepted barrier to chronic wound healing. Defining the significance, phenotype, clinical classification, and treatment guidelines has been historically lacking of evidence and based on paradigms that do not represent the scientific or clinical reality. The Problem Chronic wound bioburden is typically abundant, polymicrobial, and extremely diverse. These microbes naturally adopt biofilm phenotypes, which are quite often viable but not culturable, thereby going undetected. The failures of culture-based detection have led to abandonment of routine bioburden evaluation and aggressive treatment or, worse, to assume bioburden is not a significant barrier. Predictably, treatment regimens to address biofilm phenotypes lagged behind our diagnostic tools and understanding. Basic/Clinical Science Advances Microbial DNA-based diagnostic tools and treatment regimens have emerged, which provide and leverage objective information, resulting in a dramatic impact on outcomes. Relevance to Clinical Care Modern medicine demands decisions based on objective evidence. The diagnostic and treatment protocols reviewed herein empower clinicians to practice modern medicine with regard to bioburden, with DNA level certainty. Conclusion Bioburden is a significant barrier to healing for all chronic wounds. Molecular diagnostics provide the first objective means of assessing wound bioburden. The accuracy and comprehensive data from such diagnostic methodologies provide clinicians with the ability to employ patient-specific treatment options, targeted to each patient's microbial wound census. Based on current outcomes data, the most effective therapeutic options are topical (TPL) antibiofilm agents (ABF) combined with TPL antibiotics (ABX). In specific patients, systemic ABX and selective biocides are also appropriate, but not exclusive of ABF combined with TPL ABX. PMID:24527291

  10. One-year outcomes of women started on antiretroviral therapy during pregnancy before and after the implementation of Option B+ in Malawi: A retrospective chart review

    PubMed Central

    Kamuyango, Alfred A.; Hirschhorn, Lisa R; Wang, Wenjia; Jansen, Perry; Hoffman, Risa M.

    2015-01-01

    Objective To compare one-year outcomes of women started on antiretroviral therapy (ART) during pregnancy in the pre-Option B+ era to those in the Option B+ era. Methods A retrospective chart review was performed at three sites in Malawi. Women were included in the ‘pre-Option B+’ cohort if they started ART during pregnancy for a CD4 count < 350 cells/mm3 or WHO 3/4 condition and in the ‘Option B+’ cohort if they started ART during pregnancy regardless of CD4 count or clinical stage. One-year outcomes were compared using Fisher's exact and ANOVA F-tests. Results A higher proportion of women in the pre-Option B+ cohort started ART at WHO stage 3/4 (11.9% versus 1.1%, P < 0.001), switched ART regimens (5.9% versus 0%, P = 0.002), or died in the first year after starting treatment (3.9% versus .5%, P = 0.05). While more women in the Option B+ cohort had poor adherence or defaulted, these differences were not significant. Conclusions At our study sites, the transition to Option B+ has been associated with ART initiation in women with less advanced HIV infection, improved medication tolerability, and lower mortality. Further research is needed to better understand outcomes of Option B+. PMID:25774326

  11. One-year outcomes of women started on antiretroviral therapy during pregnancy before and after the implementation of Option B+ in Malawi: A retrospective chart review.

    PubMed

    Kamuyango, Alfred A; Hirschhorn, Lisa R; Wang, Wenjia; Jansen, Perry; Hoffman, Risa M

    2014-09-01

    To compare one-year outcomes of women started on antiretroviral therapy (ART) during pregnancy in the pre-Option B+ era to those in the Option B+ era. A retrospective chart review was performed at three sites in Malawi. Women were included in the 'pre-Option B+' cohort if they started ART during pregnancy for a CD4 count < 350 cells/mm 3 or WHO 3/4 condition and in the 'Option B+' cohort if they started ART during pregnancy regardless of CD4 count or clinical stage. One-year outcomes were compared using Fisher's exact and ANOVA F-tests. A higher proportion of women in the pre-Option B+ cohort started ART at WHO stage 3/4 (11.9% versus 1.1%, P < 0.001), switched ART regimens (5.9% versus 0%, P = 0.002), or died in the first year after starting treatment (3.9% versus .5%, P = 0.05). While more women in the Option B+ cohort had poor adherence or defaulted, these differences were not significant. At our study sites, the transition to Option B+ has been associated with ART initiation in women with less advanced HIV infection, improved medication tolerability, and lower mortality. Further research is needed to better understand outcomes of Option B+.

  12. Acquired thrombotic thrombocytopenic purpura: new therapeutic options and their optimal use.

    PubMed

    Cataland, S R; Wu, H M

    2015-06-01

    Advances in our understanding of the pathophysiology of both congenital and acquired thrombotic thrombocytopenic purpura (TTP) have led to both an increased understanding of the disease and novel approaches to therapy. The efficacy of rituximab in acquired TTP has led to consideration of rituximab as a prophylactic therapy to prevent relapse of TTP. Novel therapies that target the A1 domain of von Willebrand factor (VWF) to block the formation of microthrombotic disease have also entered clinical study and have demonstrated promise as potential therapeutic options. Additionally, a recombinant ADAMTS13 protease has been developed which may be an important therapeutic option for both congenital and acquired TTP. The development of these new therapeutic options for patients diagnosed with TTP has increased the importance of conducting prospective, randomized studies with these agents to both confirm their efficacy and more importantly understand their most appropriate role in the treatment of patients with TTP. © 2015 International Society on Thrombosis and Haemostasis.

  13. Cancer in the Family: Review of the Psychosocial Perspectives of Patients and Family Members

    ERIC Educational Resources Information Center

    Mitschke, Diane B.

    2008-01-01

    As advances in cancer care have led to more treatment options and longer survival for cancer patients, a focus on quality of life for patients and their families has gained importance. This review provides a discussion of stress and coping theory, documents the relevance of this topic area for social work practice, and illuminates the results of a…

  14. Exploring Hospice Decisions: The Road from the Institute on Aging and Social Work to an ARRA Challenge Grant

    ERIC Educational Resources Information Center

    Waldrop, Deborah

    2014-01-01

    Decisions about treatment and options for care at the end stage of an advanced chronic illness are important determinants of the quality of a person's death and of how family members adapt in bereavement. This article describes the steps taken to secure federal funding to study how people make the decision to enroll in hospice. The National…

  15. Proton Therapy for Thoracoabdominal Tumors

    NASA Astrophysics Data System (ADS)

    Sakurai, Hideyuki; Okumura, Toshiyuki; Sugahara, Shinji; Nakayama, Hidetsugu; Tokuuye, Koichi

    In advanced-stage disease of certain thoracoabdominal tumors, proton therapy (PT) with concurrent chemotherapy may be an option to reduce side effects. Several technological developments, including a respiratory gating system and implantation of fiducial markers for image guided radiation therapy (IGRT), are necessary for the treatment in thoracoabdominal tumors. In this chapter, the role of PT for tumors of the lung, the esophagus, and liver are discussed.

  16. [Lessons from 10 years of the Advanced Glaucoma Intervention Study (AGIS)].

    PubMed

    Dietlein, T S

    2005-03-01

    The 10-year results of the AGIS have revealed different outcomes of therapeutic strategies depending on ethnic factors, but also different success rates of trabeculectomy depending on age, preoperative intraocular pressure, and presence of diabetes or postoperative complications. Conclusions from the study may be limited by the fact that medical options and surgical strategies in glaucoma treatment have obviously changed during the last decade.

  17. Advanced alveolar soft part sarcoma responds to apatinib.

    PubMed

    Zhou, Yong; Tang, Fan; Wang, Yiying; Min, Li; Luo, Yi; Zhang, Wenli; Shi, Rui; Duan, Hong; Tu, Chongqi

    2017-07-25

    Alveolar soft part sarcoma (ASPS) is a rare, hypervascular soft tissue sarcoma with a low chemotherapy response rate. Here, we report an ASPS case with multiple lung metastases on initial presentation. The primary tumor, a hypervascular soft tissue mass 4.1×3.2×2.0 cm, located in the right thigh, was resected prior to chemotherapy. The patient suffered disease progression after two cycles of gemcitabine-docetaxel treatment. Immunohistochemical examination of the tumor tissue revealed strong positive staining for vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2). The patient was subsequently treated with apatinib (500 mg/day), a specific VEGFR-2 inhibitor. Treatment was well tolerated, and the patient exhibited a partial response, with the lung metastases reduced in size and number after one month of therapy. To date, 12-month progression-free survival has been achieved. Apatinib may provide an additional treatment option for metastatic ASPS, particularly in cases resistant to other chemotherapeutic options. Furtherstudies with more cases with longer follow-up times will be necessary to determine the clinical efficacy of apatinib for treatment of ASPS.

  18. Advanced alveolar soft part sarcoma responds to apatinib

    PubMed Central

    Wang, Yiying; Min, Li; Luo, Yi; Zhang, Wenli; Shi, Rui; Duan, Hong; Tu, Chongqi

    2017-01-01

    Alveolar soft part sarcoma (ASPS) is a rare, hypervascular soft tissue sarcoma with a low chemotherapy response rate. Here, we report an ASPS case with multiple lung metastases on initial presentation. The primary tumor, a hypervascular soft tissue mass 4.1×3.2×2.0 cm, located in the right thigh, was resected prior to chemotherapy. The patient suffered disease progression after two cycles of gemcitabine-docetaxel treatment. Immunohistochemical examination of the tumor tissue revealed strong positive staining for vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2). The patient was subsequently treated with apatinib (500 mg/day), a specific VEGFR-2 inhibitor. Treatment was well tolerated, and the patient exhibited a partial response, with the lung metastases reduced in size and number after one month of therapy. To date, 12-month progression-free survival has been achieved. Apatinib may provide an additional treatment option for metastatic ASPS, particularly in cases resistant to other chemotherapeutic options. Furtherstudies with more cases with longer follow-up times will be necessary to determine the clinical efficacy of apatinib for treatment of ASPS. PMID:28679123

  19. Bladder stone management: an update.

    PubMed

    Cicione, Antonio; DE Nunzio, Cosimo; Manno, Stefano; Damiano, Rocco; Posti, Alessandro; Lima, Estevao; Tubaro, Andrea; Balloni, Filippo

    2018-02-01

    Bladder stone (BS) is a rare disease curable with several options. Herein, we reviewed the specific literature in order to update the current BS management. A comprehensive systematic MEDLINE search was performed for English language reports published before April 2017 using the BS related terms, i.e. bladder-vesical calculi, lithotripsy. Then manuscripts references were screened to identify unfounded studies. Studies regarding BS in children were excluded. Retrieved studies were classified according to their main item as: etiology, diagnosis, treatment, treatment in specific illnesses and advances in BS management. Treatment option was mainly related to stone size and number as well as concomitant causative disease. However, stone nature was not analyzed in all the retrieved studies. Both trans-urethral and percutaneous lithotripsy were efficacy for stone fragmentation although the last one was suggested to avoid urethral injuries. Holmiun:Yag laser lithotripsy has made stone fragmentation feasible by using local anesthesia however in selected patients only. The urological dogma to perform concomitant prostate surgery in men with BS has been recently questioned by some observational case-series studies however, the lack of randomization and long follow up preserve that knowledge. Bladder stone is a rare and ancient disease. Nowadays new technologies have been developed in the effort to make less invasive stone treatment. The retrieved studies show that stone fragmentation can be archived by using several surgical approaches and devices whereas comparative randomized studies are still unavailable to identify the best option.

  20. Human toxocariasis: current advances in diagnostics, treatment, and interventions.

    PubMed

    Moreira, Gustavo Marçal Schmidt Garcia; Telmo, Paula de Lima; Mendonça, Marcelo; Moreira, Angela Nunes; McBride, Alan John Alexander; Scaini, Carlos James; Conceição, Fabricio Rochedo

    2014-09-01

    Toxocariasis is a neglected zoonosis caused by the nematodes Toxocara canis and Toxocara cati. This disease is widespread in many countries, reaching high prevalence independently of the economic conditions. However, the true number of cases of toxocariasis is likely to be underestimated owing to the lack of adequate surveillance programs. Although some diagnostic tests are available, their sensitivity and specificity need to be improved. In addition, treatment options for toxocariasis are limited and are non-specific. Toxocariasis is listed as one of the five most important neglected diseases by the CDC. This review presents recent advances related to the control of toxocariasis, including new immunodiagnostics, therapies, and drug formulations, as well as novel interventions using DNA vaccines, immunomodulators, and probiotics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Advances in percutaneous interventional therapies: the tricuspid valve.

    PubMed

    Jabbour, Richard J; Giannini, Francesco; Tanaka, Akihito; Mangieri, Antonio; Mikhail, Ghada W; Latib, Azeem; Colombo, Antonio

    2017-05-01

    Tricuspid regurgitation (TR) is a prevalent valve condition, with an estimated 1.6 million people in the USA living with moderate or greater severity. Functional TR, which predominantly develops due to left-sided heart disease, is the predominant condition affecting the tricuspid valve in the Western world and severe TR is associated with substantial morbidity and mortality. In part, due to a prolonged latency period with insidious symptoms, patients are often referred for surgery at advanced stages, with associated increased or prohibitive surgical risk. In addition, surgical treatment can result in high rates of recurrence. Therefore, there is an unmet need for percutaneous therapies that may provide a relatively low-risk treatment option. There are several devices with early human feasibility data available that will be reviewed in this article.

  2. Recent advances on antimicrobial wound dressing: A review.

    PubMed

    Simões, Déborah; Miguel, Sónia P; Ribeiro, Maximiano P; Coutinho, Paula; Mendonça, António G; Correia, Ilídio J

    2018-06-01

    Skin and soft tissue infections (SSTIs) have high rates of morbidity and mortality associated. Despite the successful treatment of some SSTIs, those affecting the subcutaneous tissue, fascia, or muscle delay the healing process and can lead to life-threatening conditions. Therefore, more effective treatments are required to deal with such pathological situations. Recently, wound dressings loaded with antimicrobial agents emerged as viable options to reduce wound bacterial colonization and infection, in order to improve the healing process. In this review, an overview of the most prominent antibacterial agents incorporated in wound dressings along with their mode of action is provided. Furthermore, the recent advances in the therapeutic approaches used in the clinic and some future perspectives regarding antibacterial wound dressings are also discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Emerging Approaches to Food Desensitization in Children.

    PubMed

    Hamad, Ahmad; Burks, Wesley A

    2017-05-01

    The purpose of this review is to highlight the recent advances in food desensitization in children with food allergy. Recent advancements in epicutaneous, sublingual, and oral immunotherapy for food allergy in the future may offer children with food allergy and their families a viable option to reduce risk or severity of anaphylaxis with phase III trials ongoing for two of these treatment modalities. Food allergy prevalence in children is estimated to be up to 8%. These children are at risk of significant allergic reactions and anaphylaxis. Food avoidance and use of antihistamines or epinephrine has been the standard of care for these patients. This approach also has a significant socioeconomic effects on patients and their families. Recent advancements in understanding food allergy have allowed for exploring new methods of treatment. There is an increasing interest in oral immunotherapy, epicutaneous immunotherapy, or sublingual immunotherapy for food allergy. There have been also innovative approaches to immunotherapy by modification of food allergens (to make them less allergenic while maintain their immunogenicity) or adding adjunctive treatments (probiotics, anti-IgE, etc.) to increase efficacy or safety.

  4. [Locally advanced head and neck cancers: recommendations of an expert panel and perspectives for the use of TPF regimen (docetaxel, cisplatin and fluoro-uracil) as induction therapy].

    PubMed

    Bardet, E; Bourhis, J; Cals, L; Fayette, J; Guigay, J; Hans, S; Saint-Guily, J Lacau; Lagarde, F; Lallemant, B; Milano, G; Rolland, F; Lefebvre, J-L

    2009-10-01

    The purpose of the present article was to evaluate indications, regimens, treatment modalities, and predictive factors of response to treatment in locally advanced squamous cell carcinoma of the head and neck (SCCHN). An expert panel including otolaryngology and head and neck surgery specialists, oncologists, radiotherapists and biologists analyzed the literature providing a synthesis and giving some recommendations. Findings from the main randomized phase III trials highlight that the TPF regimen (docetaxel, cisplatin, fluorouracil) represent a preferential option when induction chemotherapy is indicated in either operable or non-operable patients. Given the potential fragility of patients presenting with SCCHN, treatment modalities in routine use require applying preventive measures and tailored follow-up according to each patient's profile. As regards predictive factors of response to TPF regimen, no factor is currently validated, but ongoing trials should provide better knowledge. Progresses in induction chemotherapy have allowed improving the prognosis of patients with locally advanced SCCHN. The TPF regimen represents a major improvement in this indication, and ongoing strategic clinical trials should refine its indications.

  5. New advances in ovarian autotransplantation to restore fertility in cancer patients

    PubMed Central

    2016-01-01

    Human ovary autotransplantation is a promising option for fertility preservation of young women and girls undergoing gonadotoxic treatments for cancer or some autoimmune diseases. Although experimental, it resulted in at least 42 healthy babies worldwide. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature review was performed for all relevant full-text articles published in English from 1 January 2000 to 01 October 2015 in PubMed to explore the latest clinical and research advances of human ovary autotransplantation. Human ovary autotransplantation involves ovarian tissue extraction, freezing/thawing, and transplantation back into the same patient. Three major forms of human ovary autotransplantation exist including (a) transplantation of cortical ovarian tissue, (b) transplantation of whole ovary, and (c) transplantation of ovarian follicles (artificial ovary). According to the recent guidelines, human ovary autotransplantation is still considered experimental; however, it has unique advantages in comparison to other options of female fertility preservation. Human ovary autotransplantation (i) does not need prior ovarian stimulation, (ii) allows immediate initiation of cancer therapy, (iii) can restore both endocrine and reproductive ovarian functions, and (iv) may be the only fertility preservation option suitable for prepubertal girls or for young women with estrogen-sensitive malignancies. As any other fertility preservation option, human ovary autotransplantation has both advantages and disadvantages and may not be feasible for all cases. The major challenges facing this option are how to avoid the risk of reintroducing malignant cells and how to prolong the lifespan of ovarian transplant as well as how to improve artificial ovary results. PMID:26589603

  6. New advances in ovarian autotransplantation to restore fertility in cancer patients.

    PubMed

    Salama, Mahmoud; Woodruff, Teresa K

    2015-12-01

    Human ovary autotransplantation is a promising option for fertility preservation of young women and girls undergoing gonadotoxic treatments for cancer or some autoimmune diseases. Although experimental, it resulted in at least 42 healthy babies worldwide. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature review was performed for all relevant full-text articles published in English from 1 January 2000 to 01 October 2015 in PubMed to explore the latest clinical and research advances of human ovary autotransplantation. Human ovary autotransplantation involves ovarian tissue extraction, freezing/thawing, and transplantation back into the same patient. Three major forms of human ovary autotransplantation exist including (a) transplantation of cortical ovarian tissue, (b) transplantation of whole ovary, and (c) transplantation of ovarian follicles (artificial ovary). According to the recent guidelines, human ovary autotransplantation is still considered experimental; however, it has unique advantages in comparison to other options of female fertility preservation. Human ovary autotransplantation (i) does not need prior ovarian stimulation, (ii) allows immediate initiation of cancer therapy, (iii) can restore both endocrine and reproductive ovarian functions, and (iv) may be the only fertility preservation option suitable for prepubertal girls or for young women with estrogen-sensitive malignancies. As any other fertility preservation option, human ovary autotransplantation has both advantages and disadvantages and may not be feasible for all cases. The major challenges facing this option are how to avoid the risk of reintroducing malignant cells and how to prolong the lifespan of ovarian transplant as well as how to improve artificial ovary results.

  7. A Review of Immune Checkpoint Inhibitors for the Management of Locally Advanced or Metastatic Urothelial Carcinoma.

    PubMed

    Hanna, Kirollos S

    2017-11-01

    Urothelial carcinoma (UC) is the second most common malignancy of the genitourinary system and the sixth most common cancer in the United States. The overall incidence of UC appears to be on the decline, but death rates have remained stable. Stage IV metastatic disease is associated with only a 5% survival rate at 5 years. Gemcitabine and cisplatin combinations or dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin are the preferred regimens for individuals with advance, metastatic disease and a good performance status and organ function. Second-line therapies in this setting are limited. During the course of 1 year, five immune checkpoint inhibitors were approved for treatment of cancers in the locally advanced or metastatic setting: atezolizumab, nivolumab, durvalumab, avelumab, and pembrolizumab. Immunotherapies have played a significant role in the treatment of various cancers and have continued to expand. It is of utmost importance that practitioners include checkpoint inhibitors as treatment options for UC. Based on the limited data, pembrolizumab and atezolizumab may be the drugs of choice, as they are supported by the most influential data to date; however, further research is warranted. Ongoing clinical trials will further assess the benefits of inducing cellular immunity in the treatment of UC. These therapies mark a new landscape in the treatment of UC. In this article, the available data on immune checkpoint inhibitors for the treatment of locally advanced or metastatic UC and their place in therapy are reviewed. © 2017 Pharmacotherapy Publications, Inc.

  8. Gaining momentum: New options and opportunities for the treatment of advanced melanoma.

    PubMed

    Michielin, Olivier; Hoeller, Christoph

    2015-09-01

    Before 2011, patients with advanced or metastatic melanoma had a particularly poor long-term prognosis. Since traditional treatments failed to confer a survival benefit, patients were preferentially entered into clinical trials of investigational agents. A greater understanding of the epidemiology and biology of disease has underpinned the development of newer therapies, including six agents that have been approved in the EU, US and/or Japan: a cytotoxic T-lymphocyte antigen-4 inhibitor (ipilimumab), two programmed cell death-1 receptor inhibitors (nivolumab and pembrolizumab), two BRAF inhibitors (vemurafenib and dabrafenib) and a MEK inhibitor (trametinib). The availability of these treatments has greatly improved the outlook for patients with advanced melanoma; however, a major consideration for physicians is now to determine how best to integrate these agents into clinical practice. Therapeutic decisions are complicated by the need to consider patient and disease characteristics, and individual treatment goals, alongside the different efficacy and safety profiles of agents with varying mechanisms of action. Long-term survival, an outcome largely out of reach with traditional systemic therapies, is now a realistic goal, creating the additional need to re-establish how clinical benefit is evaluated. In this review we summarise the current treatment landscape in advanced melanoma and discuss the promise of agents still in development. We also speculate on the future of melanoma treatment and discuss how combination and sequencing approaches may be used to optimise patient care in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. [Advanced Prostate Cancer Consensus Conference 2017 : Discussion of the recommendations for diagnosis and treatment of metastatic prostate cancer by a German panel of experts].

    PubMed

    Schostak, M; König, F; Bögemann, M; Goebell, P; Hammerer, P; Machtens, S; Schwentner, C; Thomas, C; von Amsberg, G; von Rundstedt, F-C; Heidenreich, A

    2018-05-28

    In March 2017 the 'Advanced Prostate Cancer Consensus Conference' (APCCC) took place in St. Gallen (Switzerland). The APCCC-panelists are internationally well known experts. With the actual data in mind they discussed treatment options for patients with advanced prostate cancer in order to update the international APCCC-recommendations from the previous meeting in 2015. Recently these consensus recommendations have been published in "European Urology".A group of German experts discussed this year APCCC-votes during the meeting and the recommendations that were concluded from the votes from the German perspective. Reasons for an additional German discussion are country-specific variations that may have influenced the APCCC-votes und recommendations. Due to the concept of the APCCC-meeting the wording of the questions could not always be as necessary.One focus of this year consensus discussion was the treatment of metastatic castration-naive prostate cancer (mCNPC). There are new data which may also influence the therapeutic situation of patients with metastatic castration-resistant prostate cancer (mCRPC). Further points of discussion were the impact of new imaging procedures in the clinical setting as well as the treatment of oligometastatic prostate cancer.

  10. Default Options In Advance Directives Influence How Patients Set Goals For End-Of-Life Care

    PubMed Central

    Halpern, Scott D.; Loewenstein, George; Volpp, Kevin G.; Cooney, Elizabeth; Vranas, Kelly; Quill, Caroline M.; Mckenzie, Mary S.; Harhay, Michael O.; Gabler, Nicole B.; Silva, Tatiana; Arnold, Robert; Angus, Derek C.; Bryce, Cindy

    2015-01-01

    Although decisions regarding end-of-life care are personal and important, they may be influenced by the ways in which options are presented. To test this hypothesis, we randomly assigned 132 seriously ill patients to complete one of three types of advance directives. Two types had end-of-life care options already checked—a default choice—but one of these favored comfort-oriented care, and the other, life-extending care. The third type was a standard advance directive with no options checked. We found that most patients preferred comfort-oriented care, but the defaults influenced those choices. For example, 77 percent of patients in the comfort-oriented group retained that choice, while 43 percent of those in the life-extending group rejected the default choice and selected comfort-oriented care instead. Among the standard advance directive group, 61 percent of patients selected comfort-oriented care. Our findings suggest that patients may not hold deep-seated preferences regarding end-of-life care. The findings provide motivation for future research examining whether using default options in advance directives may improve important outcomes, including patients’ receipt of wanted and unwanted services, resource use, survival, and quality of life. PMID:23381535

  11. [News in neurology 2013].

    PubMed

    Spatola, Marianna; Rossetti, Andrea O; Michel, Patrick; Kuntzer, Thierry; Benninger, David; Nater, Bernard; Démonet, Jean-François; Schluep, Myriam; Du Pasquier, Renaud A; Vingerhoets, François

    2014-01-15

    In 2013, perampanel is approved as an add-on treatment for generalised and focal seizures in pharmaco-resistant epilepsy. New anticoagulants are superior to antivitamin K in stroke secondary prevention in case of atrial fibrillation. DBS remains a valid therapeutic option for advanced Parkinson's disease. Intranasal ketamine seems to reduce the intensity of severe migraine aura. High concentrations of topic capsaicin improve post-herpetic neuralgia. In Alzheimer's disease, statins might deteriorate cognitive functions. Oral immuno-modifing treatments for relapsing remitting multiple sclerosis have shown to slow cerebral atrophy progression at two years.

  12. Current insights in allergen immunotherapy.

    PubMed

    Passalacqua, Giovanni; Bagnasco, Diego; Ferrando, Matteo; Heffler, Enrico; Puggioni, Francesca; Canonica, Giorgio Walter

    2018-02-01

    Allergen-specific immunotherapy (AIT) in its subcutaneous and sublingual forms is currently a well-established and experimentally supported treatment for respiratory allergy and hymenoptera venom allergy. There have been advances in its use linked strictly to the advancement in the knowledge of the molecular mechanisms of allergy, the production of well-characterized extracts, and diagnostic techniques. The use of AIT in asthma and the application of new approaches are expanding. We briefly review the advances and concerns in the use of AIT. PubMed and Scopus. The most recent and clinically relevant literature was selected and reviewed. The introduction of high-quality products supported by large dose-finding trials has yielded better defined indications, contraindications, and modalities of use. Some specific products in tablet form have recently been approved in the United States. Sublingual immunotherapy has been found to be effective in asthma, which until recently had been a matter of debate. Another promising therapy is oral and sublingual desensitization for food allergy, for which encouraging results have recently been reported. In the near future, other options will be available, including new routes of administration (intralymphatic and epicutaneous), allergoids, engineered allergens, and peptides. The use of component-resolved diagnosis techniques will further refine and target AIT prescriptions. This condensed and updated review shows that AIT remains a viable treatment option, especially after the introduction of standardized tablets for some allergens. Food allergy and new administration routes represent a promising expansion. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  13. Lung Cancer Brain Metastases.

    PubMed

    Goldberg, Sarah B; Contessa, Joseph N; Omay, Sacit B; Chiang, Veronica

    2015-01-01

    Brain metastases are common among patients with lung cancer and have been associated with significant morbidity and limited survival. However, the treatment of brain metastases has evolved as the field has advanced in terms of central nervous system imaging, surgical technique, and radiotherapy technology. This has allowed patients to receive improved treatment with less toxicity and more durable benefit. In addition, there have been significant advances in systemic therapy for lung cancer in recent years, and several treatments including chemotherapy, targeted therapy, and immunotherapy exhibit activity in the central nervous system. Utilizing systemic therapy for treating brain metastases can avoid or delay local therapy and often allows patients to receive effective treatment for both intracranial and extracranial disease. Determining the appropriate treatment for patients with lung cancer brain metastases therefore requires a clear understanding of intracranial disease burden, tumor histology, molecular characteristics, and overall cancer prognosis. This review provides updates on the current state of surgery and radiotherapy for the treatment of brain metastases, as well as an overview of systemic therapy options that may be effective in select patients with intracranial metastases from lung cancer.

  14. [Transanal endocopic microsurgery (TEM) in advanced rectal cancer disease treatment].

    PubMed

    Paci, Marcello; Scoglio, Daniele; Ursi, Pietro; Barchetti, Luciana; Fabiani, Bernardina; Ascoli, Giada; Lezoche, Giovanni

    2010-01-01

    After Heald's revolution in 1982, who introduced the total mesorectal excision, for improve the results in terms of recurrance and survival rate, there is a need to explore new therapeutic options in treatment of sub-peritoneal rectal cancer. In particular, local excision represent more often a valid technique for non advanced rectal cancer treatment in comparison with the more invasive procedure, especially in elderly and/or in poor health patients. The introduction of TEM by Buess (transanal endoscopy microsurgery), has extended the local treatment also to classes of patients who would normally have been candidates for TME. The author gives literature's details and his experience in the use of TEM for early rectal cancer sub-peritoneal. The aim of the study is to analyze short and long term results in terms of local recurrence and survival rate comparing TEM technique with the other transanal surgery in rectal cancer treatment. Preoperative Chemio-Radio therapy and rigorous Imaging Staging are the first steps to planning surgery. It's time, for local rectal cancer, has come to make the devolution a few decades ago has been accomplished in the treatment of breast cancer

  15. Vascular Anomalies.

    PubMed

    Taghinia, Amir H; Upton, Joseph

    2018-06-12

    Vascular anomalies encompass a wide variety of clinical conditions involving the vasculature. Over the past several decades, the terminology has changed as our understanding of these conditions has improved. A well-accepted classification scheme has evolved with constant additions, updates, and revisions. Imaging techniques have also advanced with greater resolution and a better understanding of the correlation between imaging, clinical behavior, and natural history. Meanwhile, the treatment of these conditions has also changed, with greater focus on minimally invasive techniques as opposed to radical surgery. Despite these changes, surgical intervention remains a high-value option for select patients. With greater understanding of the molecular basis of these diseases, medical treatment has improved especially in severe cases where options remain limited. A multidisciplinary approach to comprehensive patient care usually yields the best outcome and is strongly encouraged. Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  16. The management of scoliosis in children with cerebral palsy: a review

    PubMed Central

    Gardner, Adrian

    2016-01-01

    Children who suffer with cerebral palsy (CP) have a significant chance of developing scoliosis during their early years and adolescence. The behavior of this scoliosis is closely associated with the severity of the CP disability and unlike idiopathic scoliosis, it continues to progress beyond skeletal maturity. Conservative measures may slow the progression of the curve, however, surgery remains the only definitive management option. Advances in surgical technique over the last 50 years have provided methods to effectively treat the deformity while also reducing complication rates. The increased risk of surgical complications with these complex patients make decisions about treatment challenging, however with careful pre-operative optimization and post-operative care, surgery can offer a significant improvement in quality of life. This review discusses the development of scoliosis in CP patient, evaluates conservative and surgical treatment options and assesses post-operative outcome. PMID:28097247

  17. Intraductal Tubulopapillary Neoplasm of the Pancreas: An Update From a Pathologist's Perspective.

    PubMed

    Rooney, Sarah L; Shi, Jiaqi

    2016-10-01

    -Intraductal tubulopapillary neoplasm (ITPN) is a rare intraductal epithelial neoplasm of the pancreas recently recognized as a distinct entity by the World Health Organization classification in 2010. It is defined as an intraductal, grossly visible, tubule-forming epithelial neoplasm with high-grade dysplasia and ductal differentiation without overt production of mucin. The diagnosis can be challenging owing to morphologic overlap with other intraductal lesions and its rarity. While recent advances in molecular genetic studies of ITPN have provided new tools to facilitate clinical diagnosis, the limited number of cases has yielded limited follow-up data to guide management. -To provide a clinical, pathologic, and molecular update on ITPN with respect to clinical presentation, imaging findings, histopathologic features, differential diagnosis, biological behavior, molecular characteristics, and treatment options. -Analysis of the pertinent literature (PubMed) and authors' research and clinical practice experience based on institutional and consultation materials. -Clinical presentation, imaging findings, histopathology, immunohistochemistry studies, molecular characteristics, prognosis, and treatment options of ITPN are reviewed. Important differential diagnoses with other intraductal neoplasms of the pancreas-especially intraductal papillary mucinous neoplasm-using histopathologic, molecular, and immunohistochemical studies, are discussed. Despite the recent progress, more studies are necessary to assess the biology and genetics of ITPN for a better understanding of the prognostic factors and treatment options.

  18. Sexual dysfunction in 2013: Advances in epidemiology, diagnosis and treatment.

    PubMed

    Lee, King Chien Joe; Fahmy, Nader; Brock, Gerald B

    2013-09-01

    To provide a contemporary review of the epidemiology, diagnosis and treatment of premature ejaculation (PE) and erectile dysfunction (ED). We searched for English-language articles published in the past 12 months using the PubMed database. Relevant articles on the subjects of sexual dysfunction, ED and PE were selected for review. Recent studies on male sexual dysfunction have provided new therapeutic possibilities. Tramadol, a well-used analgesic, has a new role in the treatment of PE. Super-selective targeting of dorsal penile nerves by surgery or cryoablative technologies might become a viable treatment option for refractory PE in the future. The role of ED as a harbinger of important comorbidities allows for the early detection and intervention of these conditions, which can optimise therapeutic outcomes. The long-term effect of chronic phosphodiesterase-5 inhibitors on endothelial dysfunction, the angiogenic potential of low-intensity extracorporeal shock wave therapy, and further advances in drug-eluting endovascular stents might in future allow clinicians to treat ED more definitively.

  19. Hepatocellular carcinoma: early-stage management challenges

    PubMed Central

    Erstad, Derek J; Tanabe, Kenneth K

    2017-01-01

    Hepatocellular carcinoma (HCC) is a major cause of cancer death and is increasing in incidence. This review focuses on HCC surveillance and treatment of early-stage disease, which are essential to improving outcomes. Multiple societies have published HCC surveillance guidelines, but screening efforts have been limited by noncompliance and overall lack of testing for patients with undiagnosed chronic liver disease. Treatment of early-stage HCC has become increasingly complex due to expanding therapeutic options and better outcomes with established treatments. Surgical indications for HCC have broadened with improved preoperative liver testing, neoadjuvant therapy, portal vein embolization, and perioperative care. Advances in post-procedural monitoring have improved efficacies of transarterial chemoembolization and radiofrequency ablation, and novel therapies involving delivery of radiochemicals are being studied in small trials. Finally, advances in liver transplantation have allowed for expanded indications beyond Milan criteria with non-inferior outcomes. More clinical trials evaluating new therapies and multimodal regimens are necessary to help clinicians design better treatment algorithms and improve outcomes. PMID:28721349

  20. Consensus statement: Palliative and supportive care in advanced heart failure.

    PubMed

    Goodlin, Sarah J; Hauptman, Paul J; Arnold, Robert; Grady, Kathleen; Hershberger, Ray E; Kutner, Jean; Masoudi, Frederick; Spertus, John; Dracup, Kathleen; Cleary, James F; Medak, Ruth; Crispell, Kathy; Piña, Ileana; Stuart, Brad; Whitney, Christy; Rector, Thomas; Teno, Joan; Renlund, Dale G

    2004-06-01

    A consensus conference was convened to define the current state and important gaps in knowledge and needed research on "Palliative and Supportive Care in Advanced Heart Failure." Evidence was drawn from expert opinion and from extensive review of the medical literature, evidence-based guidelines, and reviews. The conference identified gaps in current knowledge, practice, and research relating to prognostication, symptom management, and supportive care for advanced heart failure (HF). Specific conclusions include: (1) although supportive care should be integrated throughout treatment of patients with advanced HF, data are needed to understand how to best decrease physical and psychosocial burdens of advanced HF and to meet patient and family needs; (2) prognostication in advanced HF is difficult and data are needed to understand which patients will benefit from which interventions and how best to counsel patients with advanced HF; (3) research is needed to identify which interventions improve quality of life and best achieve the outcomes desired by patients and family members; (4) care should be coordinated between sites of care, and barriers to evidence-based practice must be addressed programmatically; and (5) more research is needed to identify the content and technique of communicating prognosis and treatment options with patients with advanced HF; physicians caring for patients with advanced HF must develop skills to better integrate the patient's preferences into the goals of care.

  1. [Clinical observation of apatinib mesylate for the treatment of multi-drug resistant advanced breast cancer].

    PubMed

    Lü, H M; Zhang, M W; Niu, L M; Zeng, H A; Yan, M

    2018-04-24

    Objective: To assess the clinical efficacy and adverse outcomes of apatinib mesylate for the treatment of multi-drug resistant advanced breast cancer. Methods: A total of 24 patients with multi-drug-resistant advanced breast cancer who underwent apatinib mesylate treatment were retrospectively analyzed at the Diagnosis and Treatment Center for Breast Cancer of Henan Cancer Hospital. Patients were reviewed every 4 weeks after initial treatment and then every 8 weeks after stable disease. Objective response rate (ORR), progression free survival (PFS), overall survival (OS) , toxicity and adverse outcomes of apatinib mesylate treatment were evaluated by imaging examinations. Results: Totally, 24 patients received apatinib mesylate at a dose of 500 mg QD. Out of the 24 patients treated, complete remission (CR) occurred in none of the patients, partial remission (PR) in 10 cases, stable disease (SD) in 10 cases, progressive disease (PD) in 4 cases, and drug with drawal in 2 cases due to adverse outcomes. Treatment with apatinib mesylate resulted in an ORR of 41.7% (10/24), disease control rate (DCR) of 83.3%, PFS of 4.7 months, and OS of 8.0 months. Adverse outcomes included proteinuria, high blood pressure, fatigue, hand-foot skin reaction (HFSR), hyperbilirubinemia, leukopenia, hair/skin pigmentation decreased. Most of the adverse events were tolerable and can be controlled after symptomatic management. Conclusions: Single-agent apatinib mesylate demonstrated the good short-term efficacy for multi-drug resistant advanced breast cancer in patients who previously underwent multiple line treatment failures. Adverse effects were controllable after symptomatic management. Treatment with apatinib mesylate maybe a viable option when other treatment modalities failed.

  2. Advances in radiotherapy for esophageal cancer

    PubMed Central

    Deng, Wei

    2018-01-01

    Esophageal cancer is a common type of malignancy worldwide and usually requires multidisciplinary care. Radiotherapy plays an important part in management of the disease. During the past few years, researchers have made much progress about radiotherapy for esophageal cancer, which was revealed in every aspect of clinical practice. Neoadjuvant chemoradiotherapy remains the standard treatment for locally advanced esophageal cancer, whereas neoadjuvant chemotherapy appears to show less toxicities and non-inferior prognosis. What’s more, definitive chemoradiotherapy could be an option for non-surgical candidates and good responders to chemoradiotherapy. Advances in radiation techniques result in higher conformity, homogeneity, more normal tissue sparing and less treatment time. Promising prognoses and less toxicities were also seen in advanced techniques. As radiation dose higher than 50 Gy obtains better local control and survival, simultaneously integrated boost is designed to increase primary tumor dosage and keep prophylactic dose to subclinical areas. Elective nodal irradiation brings about better local control but do not show advantages in survival compared with involved field irradiation (IFI). As a trend, more tolerable chemoradiotherapy regimen would be taken into account in dealing with elderly patients. PMID:29666802

  3. American power conference: Proceedings

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    1994-01-01

    The first volume of this conference contains papers on the following topics: (1) Controls, monitoring, and expert systems (Harnessing microprocessor revolution for a more competitive power industry; Plant control--Upgrades; Neural network applications); (2) Diversification and globalization (Electric utility diversification/globalization--Panel; Private power in developing countries); (3) Environment and clean air (Clean Air compliance costs; Site selection for power stations and related facilities; Electric utility trace substance emissions; Solid waste disposal and commercial use; Precipitators/fabric filters; and Effect of flow modifications on fisheries and water quality); (4) Generation--Fuel options equipment (Alternate fuels; Advances in fuel cells for electric power applications; Secondary containmentmore » and seismic requirements for petrochemical facilities; Clean coal technology demonstration; Advanced energy systems; Hydropower); (5) Nuclear operations options (Radioactive waste management and disposal; Off normal conditions; Advanced light water reactors--15 years after TMI; Structural dynamic analyses for nuclear power plants); (6) Retrofit, betterment, repowering maintenance (Project management; Improving competitiveness through process re-engineering; Central stations; Water and wastewater treatment); (7) System planning, operation demand maintenance (Transmission system access; Stability; Systems planning); (8) Transmission and distribution (Transformers; Relaying for system protection; Managing EMF effects); and (9) Education (Power engineering). 155 papers have been processed separately for inclusion on the data base.« less

  4. Blunt Cerebrovascular Injuries: Advances in Screening, Imaging, and Management Trends.

    PubMed

    Nagpal, P; Policeni, B A; Bathla, G; Khandelwal, A; Derdeyn, C; Skeete, D

    2017-10-12

    Blunt cerebrovascular injury is a relatively uncommon but sometimes life-threatening injury, particularly in patients presenting with ischemic symptoms in that vascular territory. The decision to pursue vascular imaging (generally CT angiography) is based on clinical and imaging findings. Several grading scales or screening criteria have been developed to guide the decision to pursue vascular imaging, as well as to recommend different treatment options for various injuries. The data supporting many of these guidelines and options are limited however. The purpose of this article is to review and compare these scales and criteria and the data supporting clinical efficacy and to make recommendations for future research in this area. © 2017 by American Journal of Neuroradiology.

  5. Gemcitabine-Based Chemotherapy in Adrenocortical Carcinoma: A Multicenter Study of Efficacy and Predictive Factors.

    PubMed

    Henning, Judith E K; Deutschbein, Timo; Altieri, Barbara; Steinhauer, Sonja; Kircher, Stefan; Sbiera, Silviu; Wild, Vanessa; Schlötelburg, Wiebke; Kroiss, Matthias; Perotti, Paola; Rosenwald, Andreas; Berruti, Alfredo; Fassnacht, Martin; Ronchi, Cristina L

    2017-11-01

    Adrenocortical carcinoma (ACC) is rare and confers an unfavorable prognosis in advanced stages. Other than combination chemotherapy with cisplatin, etoposide, doxorubicin, and mitotane, the second- and third-line regimens are not well-established. Gemcitabine (GEM)-based chemotherapy was suggested in a phase 2 clinical trial with 28 patients. In other solid tumors, human equilibrative nucleoside transporter type 1 (hENT1) and/or ribonucleotide reductase catalytic subunit M1 (RRM1) expression have been associated with resistance to GEM. To assess the efficacy of GEM-based chemotherapy in ACC in a real-world setting and the predictive role of molecular parameters. Retrospective multicenter study. Referral centers of university hospitals. A total of 145 patients with advanced ACC were treated with GEM-based chemotherapy (132 with concomitant capecitabine). Formalin-fixed paraffin-embedded tumor material was available for 70 patients for immunohistochemistry. The main outcome measures were progression-free survival (PFS) and an objective response to GEM-based chemotherapy. The secondary objective was the predictive role of hENT1 and RRM1. The median PFS for the patient population was 12 weeks (range, 1 to 94). A partial response or stable disease was achieved in 4.9% and 25.0% of cases, with a median duration of 26.8 weeks. Treatment was generally well tolerated, with adverse events of grade 3 or 4 occurring in 11.0% of cases. No substantial effect of hENT1 and/or RRM1 expression was observed in response to GEM-based chemotherapy. GEM-based chemotherapy is a well-tolerated, but modestly active, regimen against advanced ACC. No reliable molecular predictive factors could be identified. Owing to the scarce alternative therapeutic options, GEM-based chemotherapy remains an important option for salvage treatment for advanced ACC. Copyright © 2017 Endocrine Society

  6. Photovoltaic solar array technology required for three wide scale generating systems for terrestrial applications: rooftop, solar farm, and satellite

    NASA Technical Reports Server (NTRS)

    Berman, P. A.

    1972-01-01

    Three major options for wide-scale generation of photovoltaic energy for terrestrial use are considered: (1) rooftop array, (2) solar farm, and (3) satellite station. The rooftop array would use solar cell arrays on the roofs of residential or commercial buildings; the solar farm would consist of large ground-based arrays, probably in arid areas with high insolation; and the satellite station would consist of an orbiting solar array, many square kilometers in area. The technology advancement requirements necessary for each option are discussed, including cost reduction of solar cells and arrays, weight reduction, resistance to environmental factors, reliability, and fabrication capability, including the availability of raw materials. The majority of the technology advancement requirements are applicable to all three options, making possible a flexible basic approach regardless of the options that may eventually be chosen. No conclusions are drawn as to which option is most advantageous, since the feasibility of each option depends on the success achieved in the technology advancement requirements specified.

  7. Choosing an Advanced Therapy in Parkinson's Disease; is it an Evidence-Based Decision in Current Practice?

    PubMed

    Nijhuis, Frouke A P; van Heek, Jolien; Bloem, Bastiaan R; Post, Bart; Faber, Marjan J

    2016-07-25

    In advanced Parkinson's disease (PD), neurologists and patients face a complex decision for an advanced therapy. When choosing a treatment, the best available evidence should be combined with the professional's expertise and the patient's preferences. The objective of this study was to explore current decision-making in advanced PD. We conducted focus group discussions and individual interviews with patients (N = 20) who had received deep brain stimulation, Levodopa-Carbidopa intestinal gel, or subcutaneous apomorphine infusion, and with their caregivers (N = 16). Furthermore, we conducted semi-structured interviews with neurologists (N = 7) and PD nurse specialists (N = 3) to include the perspectives of all key players in this decision-making process. Data were analyzed by two researchers using a qualitative thematic analysis approach. Four themes representing current experiences with the decision-making process were identified: 1) information and information needs, 2) factors influencing treatment choice and individual decision strategies, 3) decision-making roles, and 4) barriers and facilitators to shared decision-making (SDM). Patient preferences were taken into account, however patients were not always provided with adequate information. The professional's expertise influenced the decision-making process in both positive and negative ways. Although professionals and patients considered SDM essential for the decision of an advanced treatment, they mentioned several barriers for the implementation in current practice. In this study we found several factors explaining why in current practice, evidence-based decision-making in advanced PD is not optimal. An important first step would be to develop objective information on all treatment options.

  8. OSTI.GOV | OSTI, US Dept of Energy Office of Scientific and Technical

    Science.gov Websites

    Information Skip to main content ☰ Submit Research Results Search Tools Public Access Policy Data Services & Dev Tools About FAQs News Sign In Create Account Sign In Create Account Department Information Search terms: Advanced search options Advanced Search OptionsAdvanced Search queries use a

  9. Online Options for Math-Advanced Students

    ERIC Educational Resources Information Center

    Wessling, Suki

    2012-01-01

    Once upon a time, a student well advanced past grade level in math would have had few choices. Advanced students would invariably outpace the skills of their elementary teachers, and due to age wouldn't have options such as going to the middle school or community college for classes. Soon thereafter, students would enter middle school only to find…

  10. [The necessary perseverance of surgery for the treatment of locally advanced colorectal cancer].

    PubMed

    Gu, Jin

    2018-03-25

    Colorectal cancer, a malignant tumor arising from the colon or rectum, is a common cancer in China, with most patients diagnosed at the advanced stage or locally advanced stage. Large tumor size results in the invasion of adjacent organs and the multiple organ involvement, which poses certain challenges for clinical treatment. When facing advanced stage colorectal cancer, some surgeons do not consider surgery, a reasonable option. However, in fact, multi-disciplinary treatment can achieve relatively good treatment outcomes in patients with advanced stage or locally advanced stage colorectal cancer. Therefore, reasonable surgery should not be hastily abandoned. For patients with large tumors without distant metastases but with multiple organ involvement, directly surgical resection is difficult, therefore, preoperative adjuvant therapy can be considered. The basic principle of surgical treatment is to accomplish maximum protection of organ functions and to perform reasonable regional lymph node dissection on the basis of achieving R0 resection. Common surgical procedures for locally advanced colorectal cancer are as follows: (1)Right-sided colon cancer with duodenal invasion: first, the colon must be freed from three directions, namely the right posterior surface of the colon, the left side of the tumor, and the upper side of the tumor inferior to the pylorus, so as to expose and assess the spatial relationship between the tumor and the duodenum; the actual tumor invasion depth in the duodenum may be shallow. (2) Splenic flexure colon cancer with invasion of the cauda pancreatis and hilum lienis: multivisceral resection must be performed without separating the attachment between the tumor and spleen. The tumor border can be found more easily through manipulations starting from the descending colon. (3) Giant sigmoid colorectal cancer with bladder invasion: invasion usually occurs at the bladder fundus. Therefore, during surgery, the attachment between the rectum and the bladder must not be separated first, but instead, an assessment must be made to determine if the bladder trigone is involved. (4) Rectal cancer with invasion of the sacrum: sacral invasion below S3 can be resected. The proximal end of the rectum to the point where it joins the sacrum is freed, and the rectum is severed. A permanent colostomy is made at the proximal end, while a h-shaped incision is made in the sacrum. The sacrum is then resected along pre-determined resection lines. (5) Rectal cancer with invasion of the uterus, adnexa, vagina, or prostate and seminal vesicles: it is usually observed in low rectal cancer. For unilateral ovarian involvement, combined resection of the bilateral adnexa should be performed. For vaginal involvement, combined resection of the vagina should be performed. For prostatic involvement, partial resection of the prostate can be performed. In general, when facing relatively complicated advanced or locally advanced colorectal cancer, clinical surgeons must adopt a positive attitude and strive zealously against the odds. With the support of multi-disciplinary treatment, the option of surgery must not be hastily abandoned in order to increase the survival chances of patients.

  11. Laparoscopic resection of locally advanced gastrointestinal stromal tumour (GIST) of the stomach following neoadjuvant imatinib chemoreduction.

    PubMed

    Berney, Christophe R

    2015-01-01

    Laparoscopic resection of locally advanced gastrointestinal stromal tumours (GISTs) is rarely offered to patients as a first line of treatment. We present two cases of locally advanced gastric GISTs successfully treated with neoadjuvant imatinib and followed up by complete laparoscopic excision of the residual tumour mass. There was no evidence of local recurrence or distant metastases after a mean follow up of more than 40 months. Over the last decade, the development of imatinib has totally revolutionized management of metastatic GISTs and it is now possible to achieve primary tumour downstaging of more than 80%. Unfortunately, current literature on laparoscopic excision of locally advanced gastric GISTs following neoadjuvant treatment of imatinib remains scarce. The present cases strongly suggest that this new therapeutic approach might become the preferred medical option in such clinical situation. Patients with locally advanced non-metastatic gastric GISTs should be offered first-line neoadjuvant. Imatinib-based cytoreductive chemotherapy as an alternative to radical debulking surgery, as a substantial proportion of them will experience significant tumour shrinkage and therefore benefit from a much less invasive laparoscopic approach. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Denali, Tulip, and Option Inferior Vena Cava Filter Retrieval: A Single Center Experience.

    PubMed

    Ramaswamy, Raja S; Jun, Emily; van Beek, Darren; Mani, Naganathan; Salter, Amber; Kim, Seung K; Akinwande, Olaguoke

    2018-04-01

    To compare the technical success of filter retrieval in Denali, Tulip, and Option inferior vena cava filters. A retrospective analysis of Denali, Gunther Tulip, and Option IVC filters was conducted. Retrieval failure rates, fluoroscopy time, sedation time, use of advanced retrieval techniques, and filter-related complications that led to retrieval failure were recorded. There were 107 Denali, 43 Option, and 39 Tulip filters deployed and removed with average dwell times of 93.5, 86.0, and 131 days, respectively. Retrieval failure rates were 0.9% for Denali, 11.6% for Option, and 5.1% for Tulip filters (Denali vs. Option p = 0.018; Denali vs. Tulip p = 0.159; Tulip vs. Option p = 0.045). Median fluoroscopy time for filter retrieval was 3.2 min for the Denali filter, 6.75 min for the Option filter, and 4.95 min for the Tulip filter (Denali vs. Option p < 0.01; Denali vs. Tulip p < 0.01; Tulip vs. Option p = 0.67). Advanced retrieval techniques were used in 0.9% of Denali filters, 21.1% in Option filters, and 10.8% in Tulip filters (Denali vs. Option p < 0.01; Denali vs. Tulip p < 0.01; Tulip vs. Option p < 0.01). Filter retrieval failure rates were significantly higher for the Option filter when compared to both the Denali and Tulip filters. Retrieval of the Denali filter required significantly less amount of fluoroscopy time and use of advanced retrieval techniques when compared to both the Option and Tulip filters. The findings of this study indicate easier retrieval of the Denali and Tulip IVC filters when compared to the Option filter.

  13. Cost-effectiveness analysis of gemcitabine, S-1 and gemcitabine plus S-1 for treatment of advanced pancreatic cancer based on GEST study.

    PubMed

    Zhou, Jing; Zhao, Rongce; Wen, Feng; Zhang, Pengfei; Tang, Ruilei; Du, Zedong; He, Xiaofeng; Zhang, Jian; Li, Qiu

    2015-04-01

    Gemcitabine (GEM) alone, S-1 alone and gemcitabine plus S-1 (GS) have shown a marginal clinical benefit for the treatment of advanced pancreatic cancer. However, there is no clearly defined optimal cost-effectiveness treatment. The objective of this study was to assess the cost-effectiveness of GEM alone, S-1 alone and GS for the treatment of advanced pancreatic cancer based on GEST study for public payers. A decision model compared GEM alone, S-1 alone and GS. Primary base case data were identified using the GEST study and the literatures. Costs were estimated from West China Hospital, Sichuan University, China, and incremental cost-effectiveness ratios (ICERs) were calculated. Survival benefits were reported in quality-adjusted life-months (QALMs). Sensitive analyses were performed by varying potentially modifiable parameters of the model. The base case analysis showed that the GEM cost $21,912 and yielded survival of 6.93 QALMs, S-1 cost $19,371 and yielded survival of 7.90 QALMs and GS cost $22,943 and yielded survival of 7.46 QALMs in the entire treatment. The one-way sensitivity analyses showed that the ICER of S-1 was driven mostly by the S-1 group utility score of stable state compared with GEM, and the GEM group utility score of progressed state played a key role on the ICER of GS compared with GEM. S-1 represents an attractive cost-effective treatment for advanced pancreatic cancer, given the favorable cost per QALM and improvement in clinical efficacy, especially the limited available treatment options.

  14. Treatments for food allergy: how close are we?

    PubMed

    Wang, Julie; Sampson, Hugh A

    2012-12-01

    Food allergy continues to be a challenging health problem, with prevalence continuing to increase and anaphylaxis still an unpredictable possibility. While improvements in diagnosis are more accurately identifying affected individuals, treatment options remain limited. The cornerstone of treatment relies on strict avoidance of the offending allergens and education regarding management of allergic reactions. Despite vigilance in avoidance, accidental ingestions and reactions continue to occur. With recent advances in the understanding of humoral and cellular immune responses in food allergy and mechanisms of tolerance, several therapeutic strategies for food allergies are currently being investigated with the hopes of providing a cure or long-term remission from food allergy.

  15. Environmental management aspects for TBT antifouling wastes from the shipyards.

    PubMed

    Kotrikla, Anna

    2009-02-01

    Tributyltin (TBT)-based antifouling paints have been successfully used for over 40 years to protect a ship's hull from biofouling. However, due to its high toxicity to marine organisms, the International Maritime Organization (IMO), in 1990, adopted a resolution recommending governments to adopt measures to eliminate antifouling paints containing TBT. High concentrations of TBT are detected in the vicinity of ports and shipyards. TBT is also usually detected in the sediment, in which it accumulates. This study reviews recent literature for the best management practices (BMPs) in order to minimize the environmental effects of TBT. The paper focuses on the evaluation of the available techniques for the removal of TBT from shipyard wastes and from the sediment. The most effective treatment methods are highlighted. BMPs include recycling of abrasive materials, use of cleaner abrasive materials, reuse of spent abrasive materials, substitution of hydroblasting by vacuum blasting or containment or ultra-high-pressure water blasting and confinement of pollution by enclosure and containment systems. The treatment of the TBT wastes by conventional biological wastewater treatment processes is probably not suitable, because the concentrations of TBT found in shipyards' wastewaters are toxic to microorganisms. Advanced technologies such as activated carbon adsorption and dissolved air flotation, in combination with filtration and coagulation-clarification, photodegradation and electrochemical treatment, are required to remove TBT. However, advanced methods should be further optimized to meet the regulatory limit of 200 ng/L. To date, only one published work examines the efficiency of incineration for the treatment of solid sandblast wastes. Regarding the treatment of sediment, land deposition of the less polluted fraction of sediment is a feasible option. Such treatment must take into account the risk of contamination of groundwater and the surroundings, and it requires extended areas of land. Other treatment methods, such as thermal and electrochemical treatment, are promising options but due to the large amounts of dredged material, they have high capital and operational costs.

  16. Medical treatment of acquired nystagmus.

    PubMed

    Ehrhardt, David; Eggenberger, Eric

    2012-11-01

    This article synthesises recent findings and addresses relevant anatomy, pathophysiologic considerations, and current treatment options for common forms of acquired nystagmus including vestibular and gaze holding dysfunction. Some forms of nystagmus have relatively specific treatments, such as baclofen for periodic alternating nystagmus, and repositioning for benign paroxysmal positional vertigo. Recent studies have brought changes to many of the treatments of nystagmus variants. Additionally, other recent advances in nystagmus treatment, like the usage of 4-aminopyridine, have added potent medications to the physician's armamentarium. Nystagmus is a commonly encountered entity in clinical practice. However, evidence supported treatments are scarce. Medical treatment of nystagmus is difficult, with often limited and variable response to pharmacologic therapies. This mandates a continued re-evaluation of patients and creation of an individualized approach to this common clinical problem.

  17. Antisense Oligonucleotide Therapy for Patients with Advanced Cancer | Center for Cancer Research

    Cancer.gov

    Colorectal cancer (CRC) is the second leading cause of cancer-related death in the U.S. Improvements in therapy have increased the survival of patients with CRC from 10 months to two years, but for patients who stop responding to treatments, such as irinotecan, options for additional therapy are limited. Antisense oligonucleotides (ASOs) may offer advantages over traditional therapies if an appropriate target can be identified.

  18. Therapeutic Innovations for Targeting Childhood Neuroblastoma: Implications of the Neurokinin-1 Receptor System.

    PubMed

    Berger, Michael; VON Schweinitz, Dietrich

    2017-11-01

    Neuroblastoma is the most common solid extracranial malignant tumor in children. Despite recent advances in the treatment of this heterogenous tumor with surgery and chemotherapy, the prognosis in advanced stages remains poor. Interestingly, neuroblastoma is one of the few solid tumors, to date, in which an effect for targeted immunotherapy has been proven in controlled clinical trials, giving hope for further advances in the treatment of this and other tumors by targeted therapy. A large array of novel therapeutic options for targeted therapy of neuroblastoma is on the horizon. To this repεrtoirε, the neurokinin-1 receptor (NK1R) system was recently added. The present article explores the most recent developments in targeting neuroblastoma cells via the NK1R and how this new knowledge could be helpful to create new anticancer therapies agains neuroblastoma and other cancers. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  19. Heart Transplant and Mechanical Circulatory Support in Patients With Advanced Heart Failure.

    PubMed

    Sánchez-Enrique, Cristina; Jorde, Ulrich P; González-Costello, José

    2017-05-01

    Patients with advanced heart failure have a poor prognosis and heart transplant is still the best treatment option. However, the scarcity of donors, long waiting times, and an increasing number of unstable patients have favored the development of mechanical circulatory support. This review summarizes the indications for heart transplant, candidate evaluation, current immunosuppression strategies, the evaluation and treatment of rejection, infectious prophylaxis, and short and long-term outcomes. Regarding mechanical circulatory support, we distinguish between short- and long-term support and the distinct strategies that can be used: bridge to decision, recovery, candidacy, transplant, and destination therapy. We then discuss indications, risk assessment, management of complications, especially with long-term support, and outcomes. Finally, we discuss future challenges and how the widespread use of long-term support for patients with advanced heart failure will only be viable if their complications and costs are reduced. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  20. Apatinib-treated advanced medullary thyroid carcinoma: a case report.

    PubMed

    Chen, Kan; Gao, Yun; Shi, Fei; Cao, Guangqiang; Bao, Jiandong

    2018-01-01

    Medullary thyroid carcinoma (MTC) is a rare malignancy originating from calcitonin-producing parafollicular C cells of the thyroid. Neither radiotherapy nor chemotherapy has demonstrated durable objective responses in patients with advanced MTC. Vandetanib and cabozantinib are the 2 tyrosine kinase inhibitors recently approved by the US Food and Drug Administration, which are not affordable for most Chinese patients. Herein, we report a case of an MTC patient who responded to apatinib, a Chinese homemade tyrosine kinase inhibitor-targeted vascular endothelial growth factor receptor. The patient was treated with thyroid lobectomy but developed MTC with extensive metastasis. The levels of serum calcitonin and carcino-embryonic antigen were much higher than the normal range. Apatinib was given at a dose of 500 mg daily and adjusted according to tolerance. Sixteen weeks following apatinib administration, the patient achieved a partial response, which lasted more than 9 weeks. No severe toxicity or drug-related side effect was observed during the treatment. Therefore, apatinib could be a new option for the treatment of advanced MTC.

  1. Epstein-Barr virus lymphoproliferative disease after hematopoietic stem cell transplant.

    PubMed

    Rouce, Rayne H; Louis, Chrystal U; Heslop, Helen E

    2014-11-01

    Epstein-Barr virus (EBV) reactivation can cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplant. Delays in reconstitution of EBV-specific T lymphocyte activity can lead to life-threatening EBV lymphoproliferative disease (EBV-PTLD). This review highlights recent advances in the understanding of pathophysiology, risk factors, diagnosis, and management of EBV viremia and PTLD. During the past decade, early detection strategies, such as serial measurement of EBV-DNA load, have helped identify high-risk patients and diagnose early lymphoproliferation. The most significant advances have come in the form of innovative treatment options, including manipulation of the balance between outgrowing EBV-infected B cells and the EBV cytotoxic T lymphocyte response, and targeting infected B cells with monoclonal antibodies, chemotherapy, unmanipulated donor lymphocytes, and donor or more recently third-party EBV cytotoxic T lymphocytes. Defining criteria for preemptive therapy remains a challenge. EBV reactivation is a significant complication after stem cell transplant. Continued improvements in risk stratification and treatment options are required to improve the morbidity and mortality caused by EBV-associated diseases. Current approaches use rituximab to deplete B cells or adoptive transfer of EBV cytotoxic T lymphocyte to reconstitute immunity. The availability of rapid EBV-specific T cell products offers the possibility of improved outcomes.

  2. Efficacy and Safety of Peginterferon Alfa-2a (40KD) in Children with Chronic Hepatitis B: The PEG-B-ACTIVE Study.

    PubMed

    Wirth, Stefan; Zhang, Hongfei; Hardikar, Winita; Schwarz, Kathleen B; Sokal, Etienne; Yang, Weibo; Fan, Huimin; Morozov, Vyacheslav; Mao, Qing; Deng, Hong; Yang Huang; Yang, Lei; Frey, Nicolas; Nasmyth-Miller, Clare; Pavlovic, Vedran; Wat, Cynthia

    2018-04-24

    Children with chronic hepatitis B (CHB) represent an area of unmet medical need, due to increased lifetime risk of CHB sequelae and limited therapeutic options compared with adult CHB patients. The PEG-B-ACTIVE (NCT01519960) phase III study evaluated peginterferon (PegIFN) alfa-2a treatment in children aged 3 to <18 years with CHB. A total of 161 hepatitis B e antigen (HBeAg)-positive immune-active patients without advanced fibrosis/cirrhosis were randomized (2:1) to PegIFN alfa-2a (Group A, n = 101) or no treatment (Group B, n = 50); patients with advanced fibrosis were assigned to PegIFN alfa-2a (Group C, n = 10). PegIFN alfa-2a was administered for 48 weeks by body surface area category, based on 180 µg/1.73m 2 . HBeAg seroconversion rates at 24 weeks post-treatment were significantly higher in Group A (25.7% vs. 6%, P = 0.0043), as were the rates of Hepatitis B s antigen (HBsAg) clearance (8.9% vs. 0%, P = 0.03), hepatitis B virus (HBV) DNA <2,000 IU/mL (28.7% vs. 2.0%, P < 0.001) or undetectable (16.8% vs. 2.0%, P = 0.0069), and alanine aminotransferase (ALT) normalization (51.5% vs. 12%, P < 0.001). Safety, including incidence of ALT flares and neutropenia, was comparable to the established PegIFN alfa-2a profile in HBV-infected adults or hepatitis C virus-infected children. Changes in growth parameters were minimal during treatment and comparable to those in untreated patients. Safety and efficacy outcomes in Group C were in line with Group A. PegIFN alfa-2a treatment of children in the immune-active phase of CHB was efficacious and well tolerated, and associated with higher incidence of HBsAg clearance than in adults. This represents an important advance to the treatment options for children with CHB. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  3. Waldenstrom Macroglobulinemia☆

    PubMed Central

    Leleu, Xavier; Roccaro, Aldo M.; Moreau, Anne-Sophie; Dupire, Sophie; Robu, Daniela; Gay, Julie; Hatjiharissi, Evdoxia; Burwik, Nicholas; Ghobrial, Irene M.

    2011-01-01

    In the past years, new developments have occurred both in the understanding of the biology of Waldenstrom Macroglobulinemia (WM) and in therapeutic options for WM. WM is a B-cell disorder characterized primarily by bone marrow infiltration with lymphoplasmacytic cells, along with demonstration of an IgM monoclonal gammopathy. Despite advances in therapy, WM remains incurable, with 5–6 years median overall survival of patients in symptomatic WM. Therapy is postponed for asymptomatic patients, and progressive anemia is the most common indication for initiation of treatment. The main therapeutic options include alkylating agents, nucleoside analogues, and rituximab. Studies involving combination chemotherapy are ongoing, and preliminary results are encouraging. No specific agent or regimen has been shown to be superior to another for treatment of WM. As such, novel therapeutic agents are needed for the treatment of WM. In ongoing efforts, we and others have sought to exploit advances made in the understanding of the biology of WM so as to better target therapeutics for this malignancy. These efforts have led to the development of several novel agents including the proteasome inhibitor bortezomib, and several Akt/mTor inhibitors, perifosine and Rad001, and immunomodulatory agents such as thalidomide and lenalidomide. Studies with monoclonal antibodies are ongoing and promising including the use of alemtuzumab, SGN-70, and the APRIL/BLYS blocking protein TACI-Ig atacicept. Other agents currently being tested in clinical trials include the PKC inhibitor enzastaurin, the natural product resveratrol, as well as the statin simvastatin. This report provides an update of the current preclinical studies and clinical efforts for the development of novel agents in the treatment of WM. PMID:18555588

  4. Radiotherapy for locally advanced resectable T3–T4 laryngeal cancer—does laryngeal preservation strategy compromise survival?

    PubMed Central

    Suzuki, Gen; Nakamura, Satoaki; Hirano, Shigeru; Yoshida, Ken; Konishi, Koji; Teshima, Teruki; Ogawa, Kazuhiko

    2018-01-01

    Abstract With the advancement of chemotherapy, a laryngeal preservation (LP) strategy was explored with the aim of improving maintenance of quality of life. Induction chemotherapy (ICT) following radiotherapy (RT) was considered a viable option because of its high initial response rate without hampering of overall survival (OS). Subsequently, concurrent chemoradiotherapy (CCRT) using CDDP became the standard of care for LP, showing the best LP ratio. For enhancing treatment intensity, ICT with taxan + CDDP + 5-FU (TPF-ICT) followed by RT showed superiority over ICT with CDDP + 5-FU (PF-ICT) followed by RT. Given that almost all randomized controlled trials investigating ICT include not only operable (endpoint, LP) but also inoperable (endpoint, OS) cases, physicians are faced with a dilemma regarding application in daily practice. In addition, increased treatment intensity causes augmentation of adverse events, which might reduce compliance. Thereafter, cetuximab, an effective drug with fewer adverse effects [bioradiotherapy (BRT)], emerged as another option. However, little evidence has confirmed its superiority over RT (or CCRT) in laryngeal cancer subpopulations. In spite of these developments, the OS of patients with laryngeal cancer has not improved for several decades. In fact, several studies indicated a decrease in OS during the 1990s, probably due to overuse of CCRT. Fortunately, the latter was not the case in most institutions. Currently, no other treatment has better OS than surgery. The eligibility criteria for LP and/or surgery largely depend upon the available expertise and experience, which differ from one institution to another. Therefore, a multidisciplinary team is required for the treatment of LP. PMID:29190391

  5. Low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors: a phase I/II report.

    PubMed

    Fan, Hui; Lu, Xuechun; Wang, Xiaohui; Liu, Yang; Guo, Bo; Zhang, Yan; Zhang, Wenying; Nie, Jing; Feng, Kaichao; Chen, Meixia; Zhang, Yajing; Wang, Yao; Shi, Fengxia; Fu, Xiaobing; Zhu, Hongli; Han, Weidong

    2014-01-01

    Aberrant DNA methylation is one of the main drivers of tumor initiation and progression. The reversibility of methylation modulation makes it an attractive target for novel anticancer therapies. Clinical studies have demonstrated that high-dose decitabine, a hypomethylating agent, results in some clinical benefits in patients with refractory advanced tumors; however, they are extremely toxic. Low doses of decitabine minimize toxicity while potentially improving the targeted effects of DNA hypomethylation. Based on these mechanisms, low-dose decitabine combined with chemoimmunotherapy may be a new treatment option for patients with refractory advanced tumors. We proposed the regimen of low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors. A favorable adverse event profile was observed in our trial that was highlighted by the finding that most of these adverse events were grades 1-2. Besides, the activity of our cohort was optimistic and the clinical benefit rate was up to 60%, and the median PFS was prolonged compared with PFS to previous treatment. We also identified a significant correlation between the PFS to previous treatment and clinical response. The low-dose DAC decitabine-based chemoimmunotherapy might be a promising protocol for improving the specificity and efficiency of patients with refractory advanced solid tumors. This trial is registered in the ClinicalTrials.gov database (identifier NCT01799083).

  6. Successful treatment using apatinib with or without docetaxel in heavily pretreated advanced non-squamous non-small cell lung cancer: A case report and literature review.

    PubMed

    Wu, Fengying; Zhang, Shijia; Gao, Guanghui; Zhao, Jing; Ren, Shengxiang; Zhou, Caicun

    2018-03-04

    Although targeted therapy directed toward driver mutations has produced a significant efficacy benefit for patients with non-small cell lung cancer (NSCLC), many patients do not possess mutations associated with the approved targeted drugs. Angiogenic agents play an important role in the therapeutic strategy for advanced NSCLC. Apatinib is a novel tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor-2. A phase II clinical trial demonstrated the survival benefit of apatinib monotherapy in advanced NSCLC. Moreover, addition of anti-angiogenic agents to chemotherapy showed robust efficacy in advanced NSCLC, regardless of tumor histology. Here, we present the case of a heavily pretreated lung adenocarcinoma patient who was treated with apatinib and apatinib continuation plus docetaxel re-challenge. He was negative for several driver genes, including EGFR, ALK, KRAS, ROS1, HER2, RET and BRAF. The previous treatment included platinum-based doublets, pemetrexed monotherapy, docetaxel plus bevacizumab, gefitinib monotherapy, nab-paclitaxel monotherapy, irinotecan plus oxaliplatin and radiotherapy. He obtained a partial response after both apatinib monotherapy and apatinib plus docetaxel treatment, with progression-free survival durations of 5 months and 6 months, respectively. This case indicated that apatinib monotherapy or apatinib plus docetaxel might be regarded as a therapeutic option for heavily pretreated patients with advanced non-squamous NSCLC.

  7. [Role of stem cell transplantation in treatment of primary cutaneous T‑cell lymphoma].

    PubMed

    Stranzenbach, R; Theurich, S; Schlaak, M

    2017-09-01

    Within the heterogeneous group of cutaneous T‑cell lymphomas (CTCL) the therapeutic options for advanced and progressive forms are particularly limited. The therapeutic value of hematopoietic stem cell transplantation in CTCL was analyzed. A literature search using the keywords "hematopoietic stem cell transplantation" and "cutaneous T‑cell lymphoma" was performed in PubMed. Studies between 1990 and 2017 were taken into account. The studies identified were analyzed for relevance and being up to date. After reviewing the currently available literature no prospective randomized studies were found. Wu et al. showed a superiority of allogeneic transplantation in a comparison of autologous and allogeneic stem cell transplantation for cutaneous lymphoma. The graft-versus-lymphoma effect plays a significant role in a prolonged progression-free survival after allogeneic transplantation. By using a non-myeloablative conditioning regimen, stem cell transplantation can also be an option for elderly patients. The most extensive long-term data after allogeneic stem cell transplantation were reported by Duarte et al. in 2014. Autologous stem cell transplantation does not currently represent a therapeutic option, whereas allogeneic stem cell transplantation for advanced cutaneous T‑cell lymphoma, using a non-myeloablative conditioning scheme, does represent a therapeutic option. However, there is no consensus on the appropriate patients and the right timing. Morbidity and mortality of complications should be taken into account. Thus, this procedure is currently subject to an individual case decision.

  8. Solar Electric and Chemical Propulsion Technology Applications to a Titan Orbiter/Lander Mission

    NASA Technical Reports Server (NTRS)

    Cupples, Michael

    2007-01-01

    Several advanced propulsion technology options were assessed for a conceptual Titan Orbiter/Lander mission. For convenience of presentation, the mission was broken into two phases: interplanetary and Titan capture. The interplanetary phase of the mission was evaluated for an advanced Solar Electric Propulsion System (SEPS), while the Titan capture phase was evaluated for state-of-art chemical propulsion (NTO/Hydrazine), three advanced chemical propulsion options (LOX/Hydrazine, Fluorine/Hydrazine, high Isp mono-propellant), and advanced tank technologies. Hence, this study was referred to as a SEPS/Chemical based option. The SEPS/Chemical study results were briefly compared to a 2002 NASA study that included two general propulsion options for the same conceptual mission: an all propulsive based mission and a SEPS/Aerocapture based mission. The SEP/Chemical study assumed identical science payload as the 2002 NASA study science payload. The SEPS/Chemical study results indicated that the Titan mission was feasible for a medium launch vehicle, an interplanetary transfer time of approximately 8 years, an advanced SEPS (30 kW), and current chemical engine technology (yet with advanced tanks) for the Titan capture. The 2002 NASA study showed the feasibility of the mission based on a somewhat smaller medium launch vehicle, an interplanetary transfer time of approximately 5.9 years, an advanced SEPS (24 kW), and advanced Aerocapture based propulsion technology for the Titan capture. Further comparisons and study results were presented for the advanced chemical and advanced tank technologies.

  9. Challenging Obesity: Patient, Provider, and Expert Perspectives on the Roles of Available and Emerging Nonsurgical Therapies

    PubMed Central

    Apovian, Caroline M.; Garvey, W. Timothy; Ryan, Donna H.

    2015-01-01

    Objective Adult obesity is recognized as a chronic disease. According to principles of chronic disease management, healthcare professionals should work collaboratively with patients to determine appropriate therapeutic strategies that address overweight and obesity, specifically considering a patient’s disease status in addition to their individual needs, preferences, and attitudes regarding treatment. A central role and responsibility of healthcare professionals in this process is to inform and educate patients about their treatment options. Although current recommendations for the management of adult obesity provide general guidance regarding safe and proper implementation of lifestyle, pharmacological, and surgical interventions, healthcare professionals need awareness of specific evidence-based information that supports individualized clinical application of these therapies. More specifically, healthcare professionals should be up-to-date on approaches that promote successful lifestyle management and be knowledgeable about newer weight loss pharmacotherapies, so they can offer patients with obesity a wide range of options to personalize their treatment. Accordingly, this educational activity has been developed to provide participants with the latest information on treatment recommendations and therapeutic advances in lifestyle intervention and pharmacotherapy for adult obesity management. Design and Methods This supplement is based on the content presented at a live CME symposium held in conjunction with ObesityWeek 2014. Results This supplement provides an expert summary of current treatment recommendations and recent advances in nonsurgical therapies for the management of adult obesity. Patient and provider perspectives on obesity management are highlighted in embedded video clips available via QR codes, and new evidence will be applied using clinically relevant case studies. Conclusions This supplement provides a topical update of obesity management, including clinical practice examples, for healthcare professionals who treat or provide care for adults with obesity. PMID:26154880

  10. Sequential treatment of icotinib after first-line pemetrexed in advanced lung adenocarcinoma with unknown EGFR gene status.

    PubMed

    Zheng, Yulong; Fang, Weijia; Deng, Jing; Zhao, Peng; Xu, Nong; Zhou, Jianying

    2014-07-01

    In non-small cell lung cancer (NSCLC), the well-developed epidermal growth factor receptor (EGFR) is an important therapeutic target. EGFR activating gene mutations have been proved strongly predictive of response to EGFR-tyrosine kinase inhibitors (TKI) in NSCLC. However, both in daily clinical practice and clinical trials, patients with unknown EGFR gene status (UN-EGFR-GS) are very common. In this study, we assessed efficacy and tolerability of sequential treatment of first-line pemetrexed followed by icotinib in Chinese advanced lung adenocarcinoma with UN-EGFR-GS. We analyzed 38 patients with advanced lung adenocarcinoma with UN-EGFR-GS treated with first-line pemetrexed-based chemotherapy followed by icotinib as maintenance or second-line therapy. The response rates to pemetrexed and icotinib were 21.1% and 42.1%, respectively. The median overall survival was 27.0 months (95% CI, 19.7-34.2 months). The 12-month overall survival probability was 68.4%. The most common toxicities observed in icotinib phase were rashes, diarrheas, and elevated aminotransferase. Subgroup analysis indicated that the overall survival is correlated with response to icotinib. The sequence of first-line pemetrexed-based chemotherapy followed by icotinib treatment is a promising option for advanced lung adenocarcinoma with UN-EGFR-GS in China.

  11. Advances in chemical pharmacotherapy to manage advanced breast cancer.

    PubMed

    Gombos, Andrea; Awada, Ahmad

    2017-01-01

    Advanced breast cancer is still incurable. However, patients diagnosed with this fatal disease live longer. The selection of systemic therapy is mainly based on molecular subtype. The aim of management in these patients is to not only improve outcome, but also to maintain quality of life. Areas covered: In this paper we focus on available treatments and drugs under late development in the three main subtypes of breast cancer: luminal (hormone receptor positive), HER2 positive and triple negative disease. Main advances during the last years have been made in the treatment of HER2 positive breast cancer with the approval of several new targeted agents. Luminal breast cancer is also a field of active clinical research. So far triple negative breast cancer remains the subtype with the worse prognosis, even though new discoveries have been made to better understand the huge heterogeneity of this type of breast cancer. Expert opinion: Several new treatment options have recently been established in metastatic breast cancer. Side effects are sometimes cumbersome for the patient and are difficult to manage easily. Thus, identification of patients who derive the most benefit is needed. In addition, collaborative efforts should integrate the genotypic fragmentation in the management and future clinical research strategies of metastatic breast cancer patients.

  12. Locally advanced squamous cell carcinoma of the head and neck: A systematic review and Bayesian network meta-analysis of the currently available treatment options.

    PubMed

    Iocca, Oreste; Farcomeni, Alessio; Di Rocco, Arianna; Di Maio, Pasquale; Golusinski, Paweł; Pardiñas López, Simón; Savo, Alfredo; Pellini, Raul; Spriano, Giuseppe

    2018-05-01

    There are still many unresolved questions in the management of locally advanced Head and Neck Cancer (HNC). Many chemotherapeutic drugs and radiotherapy fractionation schemes are available and not all have been evaluated in head-to-head clinical trials. This systematic review and Bayesian network meta-analysis aims to compare the available treatment strategies and chemotherapeutic options for locally advanced HNC. We performed a search on bibliography databases, trials registries and meetings proceedings for published and unpublished randomized trials from January 1st 2000 to December 1st 2017. Trials had to compare systemic interventions and radiotherapy (RT) approaches for locally advanced, non-metastatic HNC. Trials recruiting patients whose surgery was the first treatment option, sample size less than 20 per arm or that did not use randomization for treatment allocation were excluded from the analysis. Summary estimates on Overall survival (OS), Progression-free survival (PFS) and toxicity outcomes (grade 3-4 mucositis and neutropenia) were extracted from the included studies on a predefined database sheet. Bias was assessed through the Chocrane risk of bias assessment tool. We performed a set of pair-wise meta-analyses using a random effect model. We also performed a random effect network meta-analysis under a Bayesian framework. From the 57 included trials, including 15,723 patients, was possible to conduct analysis on 26 treatments for OS, 22 treatments for PFS and 10 treatments for toxicity. In terms of OS Concurrent chemoradiotherapy (CCRT) with cisplatin (HR 0.70, 95% CrI [credible interval] 0.62-0.78) and cetuximab on top of CCRT (HR 0.7, 95% CrI 0.5-0.97) are clearly superior to conventional RT alone. Induction chemotherapy (IC) with cisplatin and fluorouracil (HR 0.74, 95% CrI 0.52-0.95), IC with docetaxel, cisplatin, fluorouracil (HR 0.55, 95% CrI 0.54-0.89) and IC with paclitaxel, cisplatin, fluorouracil (HR 0.55, 95% CrI 0.34-0.89) before CCRT are all superior to conventional RT. CCRT with cisplatin is also superior to altered fractionation RT (HR 0.74, 95% CrI 0.64-0.84). Altered fractionation RT is not superior to conventional RT (HR 0.95, 95% CrI 0.85-1.06). Regarding PFS, CCRT with cisplatin (HR 0.72, 95% CrI 0.63-0.83), cisplatin and fluorouracil (HR 0.67, 95% CrI 0.5-0.88), carboplatin (HR 0.63, 95% CrI 0.46-0.87), carboplatin and fluorouracil (HR 0.75, 95% CrI 0.56-1), IC with cisplatin and fluorouracil (HR 0.59, 95% CrI 0.45-0.78), IC with docetaxel, cisplatin and fluorouracil (HR 0.53, 95% CrI 0.41-0.68) and IC with paclitaxel, cisplatin and fluorouracil (HR 0.59, 95% CrI 0.35-0.99) are superior to conventional RT and altered fractionation RT. IC with docetaxel, cisplatin and fluorouracil shows a significant superiority against CCRT with cisplatin (HR 0.73 95% CrI 0.58-0.92). Altered fractionation RT is not superior to conventional RT (HR 0.91, 95% CrI 0.81-1.02). Altered fractionation increases the risk of developing grade 3-4 mucositis compared to conventional RT (OR 3.74 95% 1.64-8.67) INTERPRETATION: CCRT with cisplatin remains the gold standard of treatment. Taxane based IC regimens may have a impact on locally advanced disease. Altered fractionation RT is inferior to CCRT and also does not seem to be meaningfully better than conventionally fractionated RT alone. Its role in locally advanced disease should be reevaluated. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Treatment options in HR⁺/HER2⁻ advanced breast cancer patients pretreated with nonsteroidal aromatase inhibitors: what does current evidence tell us?

    PubMed

    De Placido, Sabino; Pronzato, Paolo

    2015-01-01

    Many postmenopausal women with advanced or metastatic breast cancer (BC) receive nonsteroidal aromatase inhibitors (NSAIs). Virtually all of them experience progression, but may still gain benefit from a different endocrine or targeted agent. We indirectly compare the results of trials on endocrine or targeted treatment in HR(+)/HER2(-) mBC patients who progressed after a prior NSAI therapy. Although with the limitations of any indirect comparison, evidence suggests that only the combination of everolimus and exemestane is associated with a prolonged progression-free survival and a more evident clinical benefit than its comparators. We speculate that prior NSAI therapy can 'per se' individuate patients eligible to everolimus. More robust data from head-to-head trials will provide more grounded evidence on this issue.

  14. Continuous dopaminergic stimulation in a patient treated with daytime Levodopa-carbidopa intestinal gel and overnight Rotigotine: a case report.

    PubMed

    Imbriani, Paola; Schirinzi, Tommaso; D'Elia, Alessio; Pisani, Antonio

    2017-08-23

    Patients with Parkinson's disease (PD) receiving long-term L-Dopa therapy eventually develop motor complications with unpredictable "on-off" response fluctuations and involuntary movements, leading to progressive disability. Hence, the search for alternative therapeutic choices based on continuous dopaminergic stimulation (CDS) becomes crucial for the treatment of advanced PD. Here, we describe the case of a 70-year-old man with a 9-year history of PD, treated with daytime levodopa-carbidopa intestinal gel (LCIG) and overnight Rotigotine transdermal patch. LCIG monotherapy significantly reduced motor fluctuations and prevented the appearance of unpredictable off periods; concurrently, overnight Rotigotine improved his sleep quality and morning akinesia. Both LCIG and Rotigotine induce CDS, which conceptually mimics physiologic striatal dopamine receptor function. Hence, they both represent a good therapeutic option for the treatment of advanced PD.

  15. Advanced stage nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents: clinical characteristics and treatment outcome - a report from the SFCE & CCLG groups.

    PubMed

    Shankar, Ananth G; Roques, Gaelle; Kirkwood, Amy A; Lambilliotte, Anne; Freund, Katja; Leblanc, Thierry; Hayward, Janis; Abbou, Samuel; Ramsay, Alan D; Schmitt, Claudine; Gorde-Grosjean, Stephanie; Pacquement, Hélène; Haouy, Stephanie; Boudjemaa, Sabah; Aladjidi, Nathalie; Hall, Georgina W; Landman-Parker, Judith

    2017-04-01

    Advanced stage nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) is extremely rare in children and as a consequence, optimal treatment for this group of patients has not been established. Here we retrospectively evaluated the treatments and treatment outcomes of 41 of our patients from the UK and France with advanced stage nLPHL. Most patients received chemotherapy, some with the addition of the anti CD20 antibody rituximab or radiotherapy. Chemotherapy regimens were diverse and followed either classical Hodgkin lymphoma or B non-Hodgkin lymphoma protocols. All 41 patients achieved a complete remission with first line treatment and 40 patients are alive and well in remission. Eight patients subsequently relapsed and 1 patient died of secondary cancer (9 progression-free survival events). The median time to progression for those who progressed was 21 months (5·9-73·8). The median time since last diagnosis is 87·3 months (8·44-179·20). Thirty-six (90%), 30 (75%) and 27 (68%) patients have been in remission for more than 12, 24 and 36 months, respectively. Overall, the use of rituximab combined with multi-agent chemotherapy as first line treatment seems to be a reasonable therapeutic option. © 2017 John Wiley & Sons Ltd.

  16. Oncology of Reptiles: Diseases, Diagnosis, and Treatment.

    PubMed

    Christman, Jane; Devau, Michael; Wilson-Robles, Heather; Hoppes, Sharman; Rech, Raquel; Russell, Karen E; Heatley, J Jill

    2017-01-01

    Based on necropsy review, neoplasia in reptiles has a comparable frequency to that of mammals and birds. Reptile neoplasia is now more frequently diagnosed in clinical practice based on increased use of advanced diagnostic techniques and improvements in reptilian husbandry allowing greater longevity of these species. This article reviews the current literature on neoplasia in reptiles, and focuses on advanced diagnostics and therapeutic options for reptilian patientssuffering neoplastic disease. Although most applied clinical reptile oncology is translated from dog and cat oncology, considerations specific to reptilian patients commonly encountered in clinical practice (turtles, tortoises, snakes, and lizards) are presented. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Effectivity of advanced wastewater treatment: reduction of in vitro endocrine activity and mutagenicity but not of in vivo reproductive toxicity.

    PubMed

    Giebner, Sabrina; Ostermann, Sina; Straskraba, Susanne; Oetken, Matthias; Oehlmann, Jörg; Wagner, Martin

    2018-02-01

    Conventional wastewater treatment plants (WWTPs) have a limited capacity to eliminate micropollutants. One option to improve this is tertiary treatment. Accordingly, the WWTP Eriskirch at the German river Schussen has been upgraded with different combinations of ozonation, sand, and granulated activated carbon filtration. In this study, the removal of endocrine and genotoxic effects in vitro and reproductive toxicity in vivo was assessed in a 2-year long-term monitoring. All experiments were performed with aqueous and solid-phase extracted water samples. Untreated wastewater affected several endocrine endpoints in reporter gene assays. The conventional treatment removed the estrogenic and androgenic activity by 77 and 95 %, respectively. Nevertheless, high anti-estrogenic activities and reproductive toxicity persisted. All advanced treatment technologies further reduced the estrogenic activities by additional 69-86 % compared to conventional treatment, resulting in a complete removal of up to 97 %. In the Ames assay, we detected an ozone-induced mutagenicity, which was removed by subsequent filtration. This demonstrates that a post treatment to ozonation is needed to minimize toxic oxidative transformation products. In the reproduction test with the mudsnail Potamopyrgus antipodarum, a decreased number of embryos was observed for all wastewater samples. This indicates that reproductive toxicants were eliminated by neither the conventional nor the advanced treatment. Furthermore, aqueous samples showed higher anti-estrogenic and reproductive toxicity than extracted samples, indicating that the causative compounds are not extractable or were lost during extraction. This underlines the importance of the adequate handling of wastewater samples. Taken together, this study demonstrates that combinations of multiple advanced technologies reduce endocrine effects in vitro. However, they did not remove in vitro anti-estrogenicity and in vivo reproductive toxicity. This implies that a further optimization of advanced wastewater treatment is needed that goes beyond combining available technologies.

  18. Recent Successes and Future Directions in Immunotherapy of Cutaneous Melanoma

    PubMed Central

    Sadozai, Hassan; Gruber, Thomas; Hunger, Robert Emil; Schenk, Mirjam

    2017-01-01

    The global health burden associated with melanoma continues to increase while treatment options for metastatic melanoma are limited. Nevertheless, in the past decade, the field of cancer immunotherapy has witnessed remarkable advances for the treatment of a number of malignancies including metastatic melanoma. Although the earliest observations of an immunological antitumor response were made nearly a century ago, it was only in the past 30 years, that immunotherapy emerged as a viable therapeutic option, in particular for cutaneous melanoma. As such, melanoma remains the focus of various preclinical and clinical studies to understand the immunobiology of cancer and to test various tumor immunotherapies. Here, we review key recent developments in the field of immune-mediated therapy of melanoma. Our primary focus is on therapies that have received regulatory approval. Thus, a brief overview of the pathophysiology of melanoma is provided. The purported functions of various tumor-infiltrating immune cell subsets are described, in particular the recently described roles of intratumoral dendritic cells. The section on immunotherapies focuses on strategies that have proved to be the most clinically successful such as immune checkpoint blockade. Prospects for novel therapeutics and the potential for combinatorial approaches are delineated. Finally, we briefly discuss nanotechnology-based platforms which can in theory, activate multiple arms of immune system to fight cancer. The promising advances in the field of immunotherapy signal the dawn of a new era in cancer treatment and warrant further investigation to understand the opportunities and barriers for future progress. PMID:29276510

  19. Stress urinary incontinence in women: Current and emerging therapeutic options

    PubMed Central

    Shamout, Samer; Campeau, Lysanne

    2017-01-01

    Surgical management of stress urinary incontinence (SUI) is most commonly achieved by midurethral synthetic sling (MUS) insertion as a first-line surgical option. A great deal of research continues to evolve new management strategies to reach an optimal balance of high efficacy and minimal adverse events. This expert opinion review provides a brief and comprehensive discussion of recent advances and ongoing research in the management of SUI, with an emphasis on single-incision mini-slings, vaginal laser treatment, and cell-based therapy. It is based on data obtained from numerous published meta-analyses and original studies identified through literature search. Single-incision mini-slings appear equally effective initially compared with standard MUS (retropubic or transobturator) for the treatment of female SUI; however, this efficacy lacks durability evidence beyond one-year followup. There is a lack of sufficient clinical evidence to currently confirm long-term safety and effectiveness of cell-therapy and non-ablative vaginal laser therapy, besides suggestion of apparent initial safety. There are still significant challenges to overcome before widespread clinical practice of the latter two modalities. Future research should be aimed at identifying groups of patients who might benefit from these minimally invasive therapeutic options. PMID:28616118

  20. Cushing's syndrome in childhood: update on genetics, treatment, and outcomes.

    PubMed

    Lodish, Maya

    2015-02-01

    To provide an update on the genes associated with Cushing's syndrome in children, as well as to familiarize the clinician with recent treatment guidelines and outcome data for children with Cushing's syndrome. The list of genes associated with Cushing's syndrome continues to grow. In addition, treatment for childhood Cushing's syndrome is evolving. As long-term follow-up data on children becomes available, clinicians need to be aware of the issues that require attention. Knowledge of the specific genetic causes of Cushing's syndrome has potential implications for treatment, surveillance, and counseling. Advances in surgical technique, radiation modalities, and medical therapies offer the potential for additional treatment options in Cushing's syndrome. Early identification and management of post-treatment morbidities in children treated for Cushing's syndrome is crucial in order to optimize care.

  1. Values and options in cancer care (VOICE): study design and rationale for a patient-centered communication and decision-making intervention for physicians, patients with advanced cancer, and their caregivers

    PubMed Central

    2013-01-01

    Background Communication about prognosis and treatment choices is essential for informed decision making in advanced cancer. This article describes an investigation designed to facilitate communication and decision making among oncologists, patients with advanced cancer, and their caregivers. Methods/design The Values and Options in Cancer Care (VOICE) Study is a National Cancer Institute sponsored randomized controlled trial conducted in the Rochester/Buffalo, NY and Sacramento, CA regions. A total of 40 oncologists, approximately 400 patients with advanced cancer, and their family/friend caregivers (one per patient, when available) are expected to enroll in the study. Drawing upon ecological theory, the intervention uses a two-pronged approach: oncologists complete a multifaceted tailored educational intervention involving standardized patient instructors (SPIs), and patients and caregivers complete a coaching intervention to facilitate prioritizing and discussing questions and concerns. Follow-up data will be collected approximately quarterly for up to three years. Discussion The intervention is hypothesized to enhance patient-centered communication, quality of care, and patient outcomes. Analyses will examine the effects of the intervention on key elements of physician-patient-caregiver communication (primary outcomes), the physician-patient relationship, shared understanding of prognosis, patient well-being, and health service utilization (secondary outcomes). Trial registration Clinical Trials Identifier: NCT01485627 PMID:23570278

  2. Treatment Selection in Depression.

    PubMed

    Cohen, Zachary D; DeRubeis, Robert J

    2018-05-07

    Mental health researchers and clinicians have long sought answers to the question "What works for whom?" The goal of precision medicine is to provide evidence-based answers to this question. Treatment selection in depression aims to help each individual receive the treatment, among the available options, that is most likely to lead to a positive outcome for them. Although patient variables that are predictive of response to treatment have been identified, this knowledge has not yet translated into real-world treatment recommendations. The Personalized Advantage Index (PAI) and related approaches combine information obtained prior to the initiation of treatment into multivariable prediction models that can generate individualized predictions to help clinicians and patients select the right treatment. With increasing availability of advanced statistical modeling approaches, as well as novel predictive variables and big data, treatment selection models promise to contribute to improved outcomes in depression.

  3. Is acupuncture an acceptable option in stroke rehabilitation? A survey of stroke patients.

    PubMed

    Yam, Winnie; Wilkinson, Jenny M

    2010-01-01

    Stroke is a leading cause of morbidity and mortality and stroke survivors make up the largest group of patients in rehabilitation. These individuals also have one of the longest lengths of stay in rehabilitation. It has been suggested that acupuncture may be beneficial in post-stroke rehabilitation and in this study we examine how stroke patients value acupuncture and their perceptions of acupuncture as a rehabilitation treatment option. A questionnaire was distributed to individuals undergoing post-stroke rehabilitation at three rehabilitation centers attached to hospitals in Toronto, Canada. Two hundred and seventy-three individuals completed the questionnaire with the respondent group comprising mainly males (62%) over 65 years of age (68%). Overall 29% had used acupuncture with 16% receiving acupuncture treatment for stroke related conditions. Almost all respondents (98%) wanted to know more about acupuncture in stroke rehabilitation and 87% would consider acupuncture as a treatment option. Few (8%) reported that they had advanced level knowledge about acupuncture, with most reporting a basic (48%) or intermediate (33%) level which recognized that acupuncture used fine needles to produce a therapeutic response. Those with prior acupuncture experience expected to pay more for treatment. The main factors influencing decisions to use acupuncture were practitioner competency (84%), cost (65%) and sterilization concerns (40%). This study demonstrates that there is willingness by patients attending conventional hospital-based rehabilitation centers to consider acupuncture in stroke rehabilitation and that lack of knowledge about this treatment is not a barrier to use. Copyright 2010 Elsevier Ltd. All rights reserved.

  4. Multiple use of water in industry--the textile industry case.

    PubMed

    Rott, Ulrich

    2003-08-01

    The main aim of this article is to give a review on the state of the art of available processes for the advanced treatment of wastewater from Textile Processing Industry (TPI). After an introduction to the specific wastewater situation of the TPI the article reviews the options of process and production integrated measures. The available unit processes and examples of applied combinations of unit processes are described. A special place is given to the in-plant treatment, the reuse of the treated split flow or mixed wastewater and the recovery of textile auxiliaries and dyes.

  5. Emerging Non-Cancer Applications of Therapeutic Ultrasound

    PubMed Central

    O’Reilly, Meaghan A.; Hynynen, Kullervo

    2015-01-01

    Ultrasound therapy has been investigated for over half a century. Ultrasound can act on tissue through a variety of mechanisms, including thermal, shockwave and cavitation mechanisms, and through these can elicit different responses. Ultrasound therapy can provide a non-invasive or minimally invasive treatment option, and ultrasound technology has advanced to the point where devices can be developed to investigate a wide range of applications. This review focuses on non-cancer, clinical applications of therapeutic ultrasound, with an emphasis on treatments that have recently reached clinical investigations, and preclinical research programs that have great potential to impact patient care. PMID:25792225

  6. Carpal Tunnel Syndrome: Symptoms, Causes and Treatment Options. Literature Reviev.

    PubMed

    Zamborsky, Radoslav; Kokavec, Milan; Simko, Lukas; Bohac, Martin

    2017-01-26

    Carpal Tunnel Syndrome (CTS) is the most common form of entrapment neuropathy. Several authors have investigated the anatomical and pathophysiological features of CTS and have identified several parameters that, in combination, play a significant role in its pathophysiology. Advancement in biological research on CTS has enabled the advent of efficient diagnostic techniques such as provocative tests and nerve conduction studies. Sophisticated technologies, such as magnetic resonance imaging (MRI) and ultrasonography (US), have facilitated the diagnosis of CTS. This review article aims at consolidating the relevant medical literature pertaining to the symptoms, pathophysiology, clinical diagnosis and treatment strategies of CTS. It also compares the various methods of diagnosis and discusses their benefits and disadvantages. Finally, it sheds light on the conservative vs. surgical approach to treatment and compares them. While the surgical approach has proved to be more efficient relative to the conservative methods of steroid injections and splinting, many studies have demonstrated both advantages and adverse effects of the surgical methods. Surgical options and complications are discussed in detail. This article comprehensively summarizes all medical aspects of CTS to update medical professionals' knowledge regarding the disease.

  7. Promising personalized therapeutic options for diffuse large B-cell Lymphoma Subtypes with oncogene addictions.

    PubMed

    Steinhardt, James J; Gartenhaus, Ronald B

    2012-09-01

    Currently, two major classification systems segregate diffuse large B-cell lymphoma (DLBCL) into subtypes based on gene expression profiles and provide great insights about the oncogenic mechanisms that may be crucial for lymphomagenesis as well as prognostic information regarding response to current therapies. However, these current classification systems primarily look at expression and not dependency and are thus limited to inductive or probabilistic reasoning when evaluating alternative therapeutic options. The development of a deductive classification system that identifies subtypes in which all patients with a given phenotype require the same oncogenic drivers, and would therefore have a similar response to a rational therapy targeting the essential drivers, would significantly advance the treatment of DLBCL. This review highlights the putative drivers identified as well as the work done to identify potentially dependent populations. These studies integrated genomic analysis and functional screens to provide a rationale for targeted therapies within defined populations. Personalizing treatments by identifying patients with oncogenic dependencies via genotyping and specifically targeting the responsible drivers may constitute a novel approach for the treatment of DLBCL. ©2012 AACR.

  8. Radiation therapy and cancer control in developing countries: Can we save more lives?

    PubMed

    Baskar, Rajamanickam; Itahana, Koji

    2017-01-01

    Globally, morbidity and mortality due to cancer are predicted to increase in both men and women in the coming decades. Furthermore, it is estimated that two thirds of these cancer-related deaths will occur in low-and middle-income countries (LMIC). In addition to morbidity and mortality, cancer also causes an enormous economic burden, especially in developing countries. There are several treatment and management options for cancer including chemotherapy, radiation therapy, surgery, and palliative care. Radiotherapy or radiation therapy (RT) can be an effective treatment, especially for localized or solid cancers; about half of cancer patients receive radiation as a curative or palliative treatment. Because of its low cost, for patients from LMIC with inoperable tumors, RT may be the only option. With the overall increase in the number of cancer patients especially in resource-starved LMIC, the need for more RT facilities further affects the economic growth of those countries. Therefore, an advanced molecular-targeted and more integrated approach involving either RT alone or with surgery and improved cancer drug access worldwide are urgent needs for cancer care.

  9. Treating advanced non-small-cell lung cancer in Chinese patients: focus on icotinib

    PubMed Central

    Liang, Jun-Li; Ren, Xiao-Cang; Lin, Qiang

    2014-01-01

    Icotinib hydrochloride is an orally administered small-molecule reversible tyrosine kinase inhibitor that has been independently researched and developed and has independent intellectual property rights in the People’s Republic of China. Clinical trials have demonstrated that the response to icotinib among advanced non-small-cell lung cancer (NSCLC) patients who received at least one platinum-based chemotherapy regimen was not inferior to gefitinib. Since being launched August 2011 in the People’s Republic of China, icotinib has been widely used in clinics, and has become an important treatment option for Chinese patients with advanced NSCLC. The present study presents the Phase I, II, and III clinical trials of icotinib and discusses current clinical applications in the People’s Republic of China and future research directions. PMID:24876785

  10. A critical analysis of the cytoreductive surgery with hyperthermic intraperitoneal chemotherapy combo in the clinical management of advanced gastric cancer: an effective multimodality approach with scope for improvement

    PubMed Central

    Beeharry, Maneesh K.; Liu, Wen-Tao; Yao, Xue-Xin

    2016-01-01

    Peritoneal carcinomatosis (PC) is manifested in up to 40% of gastric cancer (GC) patients, after which their 5-year survival drops to less than 5%. The currently most acceptable treatment option for advanced GC (AGC) is systemic chemo and radio therapies with however generally very unsatisfying results and this led to a resurgence of interest in regional therapies like cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Small trials have indicated an association with prolonged survival when applying this technique to AGC manifesting with PC. High procedure-related morbidity and mortality associated with the CRS-HIPEC approach have however brought by a polemic on the merits of the latter: with the advent of regulatory approval of more effective as well as novel, more personalized treatment options in AGC, along with advances in tailoring investigational agents specifically for peritoneal delivery, there clearly is a need to outline the appropriate role of CRS-HIPEC in this disease. In a clear objective to improve the therapeutic efficiency of HIPEC, there have been immense developments in the technical aspects of this technology including the use of nanotechnology in more precise drug delivery systems (DDS) or choice of more efficient drugs such as gene-target technology, laparoscopy and so on. Henceforth, in this review, we will be highlighting the past and current status of the CRS + HIPEC procedure, shedding light on the pros and cons in order to boost up the efficiency of this multimodality approach. PMID:28138643

  11. A critical analysis of the cytoreductive surgery with hyperthermic intraperitoneal chemotherapy combo in the clinical management of advanced gastric cancer: an effective multimodality approach with scope for improvement.

    PubMed

    Beeharry, Maneesh K; Liu, Wen-Tao; Yao, Xue-Xin; Yan, Min; Zhu, Zheng-Gang

    2016-01-01

    Peritoneal carcinomatosis (PC) is manifested in up to 40% of gastric cancer (GC) patients, after which their 5-year survival drops to less than 5%. The currently most acceptable treatment option for advanced GC (AGC) is systemic chemo and radio therapies with however generally very unsatisfying results and this led to a resurgence of interest in regional therapies like cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Small trials have indicated an association with prolonged survival when applying this technique to AGC manifesting with PC. High procedure-related morbidity and mortality associated with the CRS-HIPEC approach have however brought by a polemic on the merits of the latter: with the advent of regulatory approval of more effective as well as novel, more personalized treatment options in AGC, along with advances in tailoring investigational agents specifically for peritoneal delivery, there clearly is a need to outline the appropriate role of CRS-HIPEC in this disease. In a clear objective to improve the therapeutic efficiency of HIPEC, there have been immense developments in the technical aspects of this technology including the use of nanotechnology in more precise drug delivery systems (DDS) or choice of more efficient drugs such as gene-target technology, laparoscopy and so on. Henceforth, in this review, we will be highlighting the past and current status of the CRS + HIPEC procedure, shedding light on the pros and cons in order to boost up the efficiency of this multimodality approach.

  12. 77 FR 59431 - Self-Regulatory Organizations; The Options Clearing Corporation; Notice of Filing of Advance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-27

    ... rule filing defines ``OTC option'' and ``OTC index option'' generically in order to simplify future... future OTC options accepted for clearing, OCC intends that such future OTC options will conform to the... index options that OCC may in the future clear may be fixed at such value as OCC determines and provides...

  13. Recent advances in managing differentiated thyroid cancer.

    PubMed

    Lamartina, Livia; Grani, Giorgio; Durante, Cosimo; Filetti, Sebastiano

    2018-01-01

    The main clinical challenge in the management of thyroid cancer is to avoid over-treatment and over-diagnosis in patients with lower-risk disease while promptly identifying those patients with more advanced or high-risk disease requiring aggressive treatment. In recent years, novel clinical and molecular data have emerged, allowing the development of new staging systems, predictive and prognostic tools, and treatment approaches. There has been a notable shift toward more conservative management of low- and intermediate-risk patients, characterized by less extensive surgery, more selective use of radioisotopes (for both diagnostic and therapeutic purposes), and less intensive follow-up. Furthermore, the histologic classification; tumor, node, and metastasis (TNM) staging; and American Thyroid Association risk stratification systems have been refined, and this has increased the number of patients in the low- and intermediate-risk categories. There is now a need for new, prospective data to clarify how these changing practices will impact long-term outcomes of patients with thyroid cancer, and new follow-up strategies and biomarkers are still under investigation. On the other hand, patients with more advanced or high-risk disease have a broader portfolio of options in terms of treatments and therapeutic agents, including multitarget tyrosine kinase inhibitors, more selective BRAF or MEK inhibitors, combination therapies, and immunotherapy.

  14. ESTRO ACROP guidelines for target volume definition in the treatment of locally advanced non-small cell lung cancer.

    PubMed

    Nestle, Ursula; De Ruysscher, Dirk; Ricardi, Umberto; Geets, Xavier; Belderbos, Jose; Pöttgen, Christoph; Dziadiuszko, Rafal; Peeters, Stephanie; Lievens, Yolande; Hurkmans, Coen; Slotman, Ben; Ramella, Sara; Faivre-Finn, Corinne; McDonald, Fiona; Manapov, Farkhad; Putora, Paul Martin; LePéchoux, Cécile; Van Houtte, Paul

    2018-04-01

    Radiotherapy (RT) plays a major role in the curative treatment of locally advanced non-small cell lung cancer (NSCLC). Therefore, the ACROP committee was asked by the ESTRO to provide recommendations on target volume delineation for standard clinical scenarios in definitive (chemo)radiotherapy (RT) and adjuvant RT for locally advanced NSCLC. The guidelines given here are a result of the evaluation of a structured questionnaire followed by a consensus discussion, voting and writing procedure within the committee. Hence, we provide advice for methods and time-points of diagnostics and imaging before the start of treatment planning and for the mandatory and optional imaging to be used for planning itself. Concerning target volumes, recommendations are given for GTV delineation of primary tumour and lymph nodes followed by issues related to the delineation of CTVs for definitive and adjuvant radiotherapy. In the context of PTV delineation, recommendations about the management of geometric uncertainties and target motion are given. We further provide our opinions on normal tissue delineation and organisational and responsibility questions in the process of target volume delineation. This guideline intends to contribute to the standardisation and optimisation of the process of RT treatment planning for clinical practice and prospective studies. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Biochemotherapy in patients with advanced head and neck mucosal melanoma.

    PubMed

    Bartell, Holly L; Bedikian, Agop Y; Papadopoulos, Nicholas E; Dett, Tina K; Ballo, Matthew T; Myers, Jeffrey N; Hwu, Patrick; Kim, Kevin B

    2008-12-01

    No systemic therapy regimen has been recognized as effective for metastatic mucosal melanoma of the head and neck. We retrospectively analyzed the effectiveness of biochemotherapy in patients with advanced head and neck mucosal melanoma. We evaluated the medical records of 15 patients at our institution who had received various biochemotherapy regimens for advanced head and neck mucosal melanoma. After a median follow-up duration of 13 months, 3 patients (20%) had partial response, and 4 patients (27%) had complete response. The median time to disease progression for all 15 patients was 10 months. The median overall survival duration for all patients was 22 months. Although this was a small study, our results, especially the high complete response and overall response rates, indicate that biochemotherapy for advanced head and neck mucosal melanoma should be considered as a systemic treatment option for patients with this aggressive malignancy.

  16. Shared decision making: what do clinicians need to know and why should they bother?

    PubMed

    Hoffmann, Tammy C; Légaré, France; Simmons, Magenta B; McNamara, Kevin; McCaffery, Kirsten; Trevena, Lyndal J; Hudson, Ben; Glasziou, Paul P; Del Mar, Christopher B

    2014-07-07

    Shared decision making enables a clinician and patient to participate jointly in making a health decision, having discussed the options and their benefits and harms, and having considered the patient's values, preferences and circumstances. It is not a single step to be added into a consultation, but a process that can be used to guide decisions about screening, investigations and treatments. The benefits of shared decision making include enabling evidence and patients' preferences to be incorporated into a consultation; improving patient knowledge, risk perception accuracy and patient-clinician communication; and reducing decisional conflict, feeling uninformed and inappropriate use of tests and treatments. Various approaches can be used to guide clinicians through the process. We elaborate on five simple questions that can be used: What will happen if the patient waits and watches? What are the test or treatment options? What are the benefits and harms of each option? How do the benefits and harms weigh up for the patient? Does the patient have enough information to make a choice? Although shared decision making can occur without tools, various types of decision support tools now exist to facilitate it. Misconceptions about shared decision making are hampering its implementation. We address the barriers, as perceived by clinicians. Despite numerous international initiatives to advance shared decision making, very little has occurred in Australia. Consequently, we are lagging behind many other countries and should act urgently.

  17. Targeting Heat Shock Protein 90 for the Treatment of Malignant Pheochromocytoma

    PubMed Central

    Giubellino, Alessio; Sourbier, Carole; Lee, Min-Jung; Scroggins, Brad; Bullova, Petra; Landau, Michael; Ying, Weiwen; Neckers, Len

    2013-01-01

    Metastatic pheochromocytoma represents one of the major clinical challenges in the field of neuroendocrine oncology. Recent molecular characterization of pheochromocytoma suggests new treatment options with targeted therapies. In this study we investigated the 90 kDa heat shock protein (Hsp90) as a potential therapeutic target for advanced pheochromocytoma. Both the first generation, natural product Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin), and the second-generation synthetic Hsp90 inhibitor STA-9090 (ganetespib) demonstrated potent inhibition of proliferation and migration of pheochromocytoma cell lines and induced degradation of key Hsp90 clients. Furthermore, ganetespib induced dose-dependent cytotoxicity in primary pheochromocytoma cells. Using metastatic models of pheochromocytoma, we demonstrate the efficacy of 17-AAG and ganetespib in reducing metastatic burden and increasing survival. Levels of Hsp70 in plasma from the xenograft studies served as a proximal biomarker of drug treatment. Our study suggests that targeting Hsp90 may benefit patients with advanced pheochromocytoma. PMID:23457505

  18. Clinical potential of nintedanib for the second-line treatment of advanced non-small-cell lung cancer: current evidence.

    PubMed

    Rothschild, Sacha I

    2014-01-01

    The therapeutic landscape in non-small-cell lung cancer (NSCLC) is changing. The description of molecular alterations leading to NSCLC carcinogenesis and progression (so-called oncogenic driver mutations) and the development of targeted agents interfering with the tumor-promoting intracellular signaling pathways have improved the outcome for many patients with advanced/metastatic NSCLC. However, many patients with stage IV NSCLC do not have one of the targetable predictive biomarkers, and are therefore in need of classical chemotherapy. This especially applies to squamous cell cancer. A platinum-based doublet chemotherapy is the standard of care for patients with stage IV NSCLC. As second-line therapies, docetaxel, pemetrexed, and the EGFR tyrosine-kinase inhibitor erlotinib have demonstrated benefit in Phase III randomized trials. Recently, the addition of the angiokinase inhibitor nintedanib to docetaxel has proven efficacious, and is a new treatment option in the second-line setting. Preclinical and clinical data of nintedanib for the treatment of lung cancer patients are reviewed here.

  19. Clinical potential of nintedanib for the second-line treatment of advanced non-small-cell lung cancer: current evidence

    PubMed Central

    Rothschild, Sacha I

    2014-01-01

    The therapeutic landscape in non-small-cell lung cancer (NSCLC) is changing. The description of molecular alterations leading to NSCLC carcinogenesis and progression (so-called oncogenic driver mutations) and the development of targeted agents interfering with the tumor-promoting intracellular signaling pathways have improved the outcome for many patients with advanced/metastatic NSCLC. However, many patients with stage IV NSCLC do not have one of the targetable predictive biomarkers, and are therefore in need of classical chemotherapy. This especially applies to squamous cell cancer. A platinum-based doublet chemotherapy is the standard of care for patients with stage IV NSCLC. As second-line therapies, docetaxel, pemetrexed, and the EGFR tyrosine-kinase inhibitor erlotinib have demonstrated benefit in Phase III randomized trials. Recently, the addition of the angiokinase inhibitor nintedanib to docetaxel has proven efficacious, and is a new treatment option in the second-line setting. Preclinical and clinical data of nintedanib for the treatment of lung cancer patients are reviewed here. PMID:28210142

  20. Immunotherapies in CLL.

    PubMed

    Park, Jae H; Brentjens, Renier J

    2013-01-01

    Chronic lymphocytic leukemia (CLL) is the most frequently diagnosed leukemia in the Western world, yet remains essentially incurable. Although initial chemotherapy response rates are high, patients invariably relapse and subsequently develop resistance to chemotherapy. For the moment, allogeneic hematopoietic stem cell transplant (allo-HSCT) remains the only potentially curative treatment for patients with CLL, but it is associated with high rates of treatment-related mortality. Immune-based treatment strategies to augment the cytotoxic potential of T cells offer exciting new treatment options for patients with CLL, and provide a unique and powerful spectrum of tools distinct from traditional chemotherapy. Among the most novel and promising of these approaches are chimeric antigen receptor (CAR)-based cell therapies that combine advances in genetic engineering and adoptive immunotherapy.

  1. Hypoplastic left heart syndrome - a review of supportive percutaneous treatment.

    PubMed

    Moszura, Tomasz; Góreczny, Sebastian; Dryżek, Paweł

    2014-01-01

    Due to the complex anatomical and haemodynamic consequences of hypoplastic left heart syndrome (HLHS), patients with the condition require multistage surgical and supportive interventional treatment. Percutaneous interventions may be required between each stage of surgical palliation, sometimes simultaneously with surgery as hybrid interventions, or after completion of multistage treatment. Recent advances in the field of interventional cardiology, including new devices and techniques, have significantly contributed to improving results of multistage HLHS palliation. Knowledge of the potential interventional options as well as the limitation of percutaneous interventions will enable the creation of safe and effective treatment protocols in this highly challenging group of patients. In this comprehensive review we discuss the types, goals, and potential complications of transcatheter interventions in patients with HLHS.

  2. Small Satellite Propulsion Options

    NASA Technical Reports Server (NTRS)

    Myers, Roger M.; Oleson, Steven R.; Curran, Francis M.; Schneider, Steven J.

    1994-01-01

    Advanced chemical and low power electric propulsion offer attractive options for small satellite propulsion. Applications include orbit raising, orbit maintenance, attitude control, repositioning, and deorbit of both Earth-space and planetary spacecraft. Potential propulsion technologies for these functions include high pressure Ir/Re bipropellant engines, very low power arcjets, Hall thrusters, and pulsed plasma thrusters, all of which have been shown to operate in manners consistent with currently planned small satellites. Mission analyses show that insertion of advanced propulsion technologies enables and/or greatly enhances many planned small satellite missions. Examples of commercial, DoD, and NASA missions are provided to illustrate the potential benefits of using advanced propulsion options on small satellites.

  3. Stroke: advances in medical therapy and acute stroke intervention.

    PubMed

    Barrett, Kevin M; Lal, Brajesh K; Meschia, James F

    2015-10-01

    Evidence-based therapeutic options for stroke continue to emerge based on results from well-designed clinical studies. Ischemic stroke far exceeds hemorrhagic stroke in terms of prevalence and incidence, both in the USA and worldwide. The public health effect of reducing death and disability related to ischemic stroke justifies the resources that have been invested in identifying safe and effective treatments. The emergence of novel oral anticoagulants for ischemic stroke prevention in atrial fibrillation has introduced complexity to clinical decision making for patients with this common cardiac arrhythmia. Some accepted ischemic stroke preventative strategies, such as carotid revascularization for asymptomatic carotid stenosis, require reassessment, given advances in risk factor management, antithrombotic therapy, and surgical techniques. Intra-arterial therapy, particularly with stent retrievers after intravenous tissue plasminogen activator, has recently been demonstrated to improve functional outcomes and will require investment in system-based care models to ensure that effective treatments are received by patients in a timely fashion. The purpose of this review is to describe recent advances in medical and surgical approaches to ischemic stroke prevention and acute treatment. Results from recently published clinical trials will be highlighted along with ongoing clinical trials addressing key questions in ischemic stroke management and prevention where equipoise remains.

  4. Apatinib is effective for treatment of advanced hepatocellular carcinoma.

    PubMed

    Kong, Yinlong; Sun, Lin; Hou, Zhenyu; Zhang, Yongqiang; Chen, Ping; Cui, Yunlong; Zhu, Xiaolin; Song, Tianqiang; Li, Qiang; Li, Huikai; Zhang, Ti; Qin, Lunxiu

    2017-12-01

    As treatment options for hepatocellular carcinoma (HCC) are currently limited, we evaluated the efficacy and safety of oral apatinib, a VEGFR-2 inhibitor, on patients with advanced HCC. Twenty-two patients from Tianjin Medical University Cancer Institute and Hospital were enrolled for evaluation. Apatinib was administered at 500 mg/day or 250 mg/day continuously. Clinical endpoints were time to disease progression (TTP), overall survival (OS), and safety. The median TTP of treated patients was 10.4 months (95% CI 3.4 -17.5). At the last follow-up, 50% patients had survived longer than 11.4 months from the first dose. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) rates were 0%, 40.9%, 40.9%, and 18.2%, respectively. The most common apatinib-related adverse events were hand-foot skin reaction (HFSR) (81.8%) and diarrhea (77.3%). Hypertension (27.3%) and HFSR (13.6%) were the most frequent grade 3/4 adverse events. In summary, results of this small study indicate that apatinib is well tolerated and extremely effective for the treatment of advanced HCC. It is therefore imperative to design and carry out well-controlled clinical trials to confirm its efficacy.

  5. Isolated limb infusion with fotemustine after dacarbazine chemosensitisation for inoperable loco-regional melanoma recurrence.

    PubMed

    Bonenkamp, J J; Thompson, J F; de Wilt, J H; Doubrovsky, A; de Faria Lima, R; Kam, P C A

    2004-12-01

    Isolated limb infusion (ILI) is a simple yet effective alternative to conventional isolated limb perfusion for the treatment of advanced melanoma of the extremities. The study group comprised 13 patients with very advanced limb disease who had failed to achieve a satisfactory response to one or more ILIs with melphalan, and in whom amputation was the only other realistic treatment option. The aim of this study was to evaluate the efficacy and toxicity of ILI with fotemustine after systemic chemosensitisation with dacarbazine (DTIC). Complete remission was achieved in four patients and partial remission in eight patients, with a median response duration of 3 months. Limb salvage was achieved in five of 12 assessable patients (42%). Limb toxicity peaked 9 days after ILI; two patients experienced Wieberdink grade IV (severe) toxicity and four patients had grade V toxicity (requiring early amputation). ILI with fotemustine after DTIC chemosensitisation can be successful when gross limb disease has not been controlled by one or more ILIs with melphalan. However, it cannot be recommended as a routine method of treatment for advanced melanoma of the extremities because of the high incidence of severe limb toxicity.

  6. Advances in the treatment of melasma: a review of the recent literature.

    PubMed

    Ball Arefiev, Katharine L; Hantash, Basil M

    2012-07-01

    Melasma is an acquired pigmentary disorder classically manifesting as symmetric hyperpigmented macules and patches on the face. It most commonly affects women of reproductive age with darker skin tones but may also affect adolescents, older women, and men. Although its pathogenesis remains unclear, known risk factors include ultraviolet radiation, hormonal variations of pregnancy, thyroid disease, oral contraceptives, and antiseizure medications. Hydroquinone-containing topical agents are the current standard for melasma treatment, but concern about side effects and long-term safety has spurred efforts to develop alternative treatment options. To review recent advances in melasma treatment. MEDLINE was searched from 2006 to the present for randomized controlled trials (RCTs) of melasma treatments. Nineteen published RCTs were found covering interventions such as topical therapies, chemical peels, and electromagnetic devices. The outcomes of the studies were summarized into tabular form for easy reference and comparison. Although melasma is difficult to treat, novel therapeutic modalities have emerged. Further RCT need to be performed to better assess the safety and efficacy of these novel treatment modalities, especially for the long-term maintenance of melasma. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

  7. Evidence in immunotherapy for paediatric respiratory allergy: Advances and recommendations.

    PubMed

    Tortajada-Girbés, M; Mesa Del Castillo, M; Larramona, H; Lucas, J M; Álvaro, M; Tabar, A I; Jerez, M J; Martínez-Cañavate, A

    2016-11-01

    Allergic respiratory diseases are major health problems in paediatric population due their high level of prevalence and chronicity, and to their relevance in the costs and quality of life. One of the most important risk factors for the development of airway diseases in children and adolescents is atopy. The mainstays for the treatment of these diseases are avoiding allergens, controlling symptoms, and preventing them through sustained desensitization by allergen immunotherapy (AIT). AIT is a treatment option that consists in the administration of increasing amounts of allergens to modify the biological response to them, inducing long-term tolerance even after treatment has ended. This treatment approach has shown to decrease symptoms and improve quality of life, becoming cost effective for a large number of patients. In addition, it is considered the only treatment that can influence the natural course of the disease by targeting the cause of the allergic inflammatory response. The aim of this publication is to reflect the advances of AIT in the diagnosis and treatment of allergic respiratory diseases in children and adolescents reviewing articles published since 2000, establishing evidence categories to support the strength of the recommendations based on evidence. The first part of the article covers the prerequisite issues to understand how AIT is effective, such as the correct etiologic and clinical diagnosis of allergic respiratory diseases. Following this, the article outlines the advancements in understanding the mechanisms by which AIT achieve immune tolerance to allergens. Administration routes, treatment regimens, dose and duration, efficacy, safety, and factors associated with adherence are also reviewed. Finally, the article reviews future advances in the research of AIT. Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

  8. Appropriate drinking water treatment processes for organic micropollutants removal based on experimental and model studies - a multi-criteria analysis study.

    PubMed

    Sudhakaran, Sairam; Lattemann, Sabine; Amy, Gary L

    2013-01-01

    The presence of organic micropollutants (OMPs), pharmaceuticals and personal care products (PPCPs) in potable water is of great environmental and public health concern. OMPs are included in the priority list of contaminants in United States EPA and European framework directives. Advanced treatment processes such as reverse osmosis, nanofiltration, ozonation and adsorption are the usual industry-recommended processes for OMPs removal, however, natural systems, e.g., riverbank filtration and constructed wetlands, are also potentially efficient options for OMPs removal. In this study, a decision support system (DSS) based on multi-criteria analysis (MCA) was created to compare processes for OMPs removal under various criteria. Multi-criteria analysis (MCA), a transparent and reliable procedure, was adopted. Models were built for both experimental and predicted percent-removals for a range of OMPs reflecting different physicochemical properties. The experimental percent-removals for several processes (riverbank filtration (RBF), ozonation, advanced oxidation, adsorption, reverse osmosis, and nanofiltration) were considered. The predicted percent-removals were taken from validated quantitative structure activity relationship (QSAR) models. Analytical methods to detect OMPs in water are very laborious, thus a modeling approach such as QSAR is an attractive option. A survey among two groups of participants including academics (PhD students and post-doctoral research associates) and industry (managers and operators) representatives was conducted to assign weights for the following criteria: treatability, costs, technical considerations, sustainability and time. The process rankings varied depending on the contaminant species and personal preferences (weights). The results indicated that RBF and oxidation were preferable over adsorption and membranes processes. The results also suggest that the use of a hybrid treatment process, e.g., combining a natural system with an advanced treatment (oxidation) process, may provide benefits for OMPs removal. The proposed DSS can be used as a screening tool for experimental planning or a feasibility study preceding the main treatment system selection and design. It can also be considered as an aid in assessing a multi-barrier approach to remove OMPs. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Fixed-Dose-Rate Gemcitabine: A Viable First-Line Treatment Option for Advanced Pancreatic and Biliary Tract Cancer

    PubMed Central

    Milella, Michele; Pino, Maria Simona; Bossone, Giandominik; Marolla, Paolo; Sperduti, Isabella; Cognetti, Francesco

    2010-01-01

    Background. We have already reported on fixed-dose-rate gemcitabine (FDR-Gem) in advanced, inoperable pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancer (BTC) in the context of a formal phase II study; building on that experience, we have now expanded the study to reach a cumulative accrual of 106 patients. Methods. One hundred six patients (PDAC/BTC, 75/31) were treated with weekly FDR-Gem (1,000 mg/m2 infused at 10 mg/m2 per minute). Patient characteristics included: male-to-female ratio, 0.83; median age, 63 years (range, 28–82); metastatic disease in 66% of patients; and an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0–1 in 81% of patients. Results. The median and total number of treatment weeks delivered were 8 (range, 2–22) and 1,154, respectively. Thirteen percent of patients achieved an objective response, 42% experienced a positive clinical benefit response, and 54% achieved a >50% reduction in serum cancer antigen (CA)19.9 levels. The median progression-free survival (PFS) and overall survival (OS) times for the entire population were 4.4 months (95% confidence interval [CI], 3.5–5.1 months) and 7.7 months (95% CI, 6.3–8.8 months), respectively, with 20% of patients alive at 1 year. On multivariate analysis, a CA19.9 reduction >50% and baseline ECOG PS score of 0 were the only independent predictors of PFS and OS, respectively. Treatment was well tolerated, with grade 3–4 neutropenia in 47 of 1,154 treatment weeks (4.1%), and grade 3 anemia and thrombocytopenia in 8 of 1,154 (0.7%) and 16 of 1,154 (1.4%) treatment weeks, respectively. Conclusions. Currently available evidence, including this updated analysis, supports the use of FDR-Gem as a first-line option in advanced PDAC, and possibly in BTC, patients and prompts the continued evaluation of this approach in combination regimens. PMID:20189980

  10. Nanotechnology for the Prevention and Treatment of Cataract.

    PubMed

    Cetinel, Sibel; Montemagno, Carlo

    2015-01-01

    The purpose of this article was to review recent advances in the applications of nanotechnology in cataract treatment and prevention strategies. A literature review on the use of nanotechnology for the prevention and treatment of cataract was done. Research articles about nanotechnology-based treatments and prevention technologies for cataract were searched on Web of Science, and the most recent advances were reported. Nonsteroid anti-inflammatory drugs, natural antioxidants, biologic and chemical chaperones, and chaperones such as molecules have found great application in preventing and treating cataracts. Current scientific research on new treatment strategies, which focuses on the biochemical basis of the disease, will likely result in new anticataract agents. However, none of the drug formulations will be approved for use unless efficient delivery is promised. Nanoparticle engineering together with biomimetic strategies enable the development of next-generation, more efficient, less complex, and personalized treatments. The only currently available treatment for cataracts, surgical replacement of the opacified lens, is not an easily accessible option in developing countries. New treatment strategies based on topical drugs would enable treatment to reach massive populations facing the threat of blindness and more effectively deal with the postsurgical complications. Nanotechnology plays a key role in improving drug delivery systems with enhanced controlled release, targeted delivery, and bioavailability to overcome diffusion limitations in the eye.

  11. VEGF inhibitors in metastatic renal cell carcinoma: current therapies and future perspective.

    PubMed

    Choueiri, Toni K

    2011-08-01

    Metastatic renal cell carcinoma (RCC) is predominantly refractory to treatment with traditional cytotoxic chemotherapies, and until recently management options were limited to immunotherapy, palliative care, or phase I trials. The past five years have witnessed a major change in the treatment of advanced RCC with the introduction of targeted therapies that derive their efficacy through affecting angiogenesis. The main class of agents involves drugs that target the vascular endothelial growth factor (VEGF). Several VEGF inhibitors are now approved for the treatment of metastatic RCC. The field is expanding rapidly with goals including 1) developing novel more potent and better tolerated agents and 2) defining the role of combination and sequential anti-VEGF regimens.

  12. Specific Adoptive Cellular Immunotherapy in Allogeneic Stem Cell Transplantation.

    PubMed

    Audehm, Stefan; Krackhardt, Angela M

    2017-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a treatment option for a diversity of advanced hematopoietic malignancies providing hope for long-term responses especially due to immunogenic effects associated with the treatment modality. Despite respectable progress in the field, relapses and/or opportunistic infections are major reasons for the high treatment-related mortality. However, a number of novel immunotherapeutic approaches using defined cell populations have been developed to directly target residual malignant cells as well as defined infectious diseases. We here provide an overview of current adoptive cellular immunotherapies in the context of allo-HSCT and close with an outlook on new directions within the field. © 2017 S. Karger GmbH, Freiburg.

  13. Chemotherapy for hepatocellular carcinoma: The present and the future

    PubMed Central

    Le Grazie, Marco; Biagini, Maria Rosa; Tarocchi, Mirko; Polvani, Simone; Galli, Andrea

    2017-01-01

    Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver. Its relationship to chronic liver diseases, in particular cirrhosis, develops on a background of viral hepatitis, excessive alcohol intake or metabolic steatohepatitis, leads to a high incidence and prevalence of this neoplasia worldwide. Despite the spread of HCC, its treatment it’s still a hard challenge, due to high rate of late diagnosis and to lack of therapeutic options for advanced disease. In fact radical surgery and liver transplantation, the most radical therapeutic approaches, are indicated only in case of early diagnosis. Even local therapies, such as transarterial chemoembolization, find limited indications, leading to an important problem regarding treatment of advanced disease. In this situation, until terminal HCC occurs, systemic therapy is the only possible approach, with sorafenib as the only standard treatment available. Anyway, the efficacy of this drug is limited and many efforts are necessary to understand who could benefit more with this treatment. Therefore, other molecules for a targeted therapy were evaluated, but only regorafenib showed promising results. Beside molecular target therapy, also cytotoxic drugs, in particular oxaliplatin- and gemcitabine-based regimens, and immune-checkpoint inhibitors were tested with interesting results. The future of the treatment of this neoplasia is linked to our ability to understand its mechanisms of resistance and to find novel therapeutic targets, with the objective to purpose individualized approaches to patients affected by advanced HCC. PMID:28824742

  14. Chemotherapy for hepatocellular carcinoma: The present and the future.

    PubMed

    Le Grazie, Marco; Biagini, Maria Rosa; Tarocchi, Mirko; Polvani, Simone; Galli, Andrea

    2017-07-28

    Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver. Its relationship to chronic liver diseases, in particular cirrhosis, develops on a background of viral hepatitis, excessive alcohol intake or metabolic steatohepatitis, leads to a high incidence and prevalence of this neoplasia worldwide. Despite the spread of HCC, its treatment it's still a hard challenge, due to high rate of late diagnosis and to lack of therapeutic options for advanced disease. In fact radical surgery and liver transplantation, the most radical therapeutic approaches, are indicated only in case of early diagnosis. Even local therapies, such as transarterial chemoembolization, find limited indications, leading to an important problem regarding treatment of advanced disease. In this situation, until terminal HCC occurs, systemic therapy is the only possible approach, with sorafenib as the only standard treatment available. Anyway, the efficacy of this drug is limited and many efforts are necessary to understand who could benefit more with this treatment. Therefore, other molecules for a targeted therapy were evaluated, but only regorafenib showed promising results. Beside molecular target therapy, also cytotoxic drugs, in particular oxaliplatin- and gemcitabine-based regimens, and immune-checkpoint inhibitors were tested with interesting results. The future of the treatment of this neoplasia is linked to our ability to understand its mechanisms of resistance and to find novel therapeutic targets, with the objective to purpose individualized approaches to patients affected by advanced HCC.

  15. A review of soft-tissue sarcomas: translation of biological advances into treatment measures

    PubMed Central

    Mann, Michael J; Tolani, Bhairavi

    2018-01-01

    Soft-tissue sarcomas are rare malignant tumors arising from connective tissues and have an overall incidence of about five per 100,000 per year. While this diverse family of malignancies comprises over 100 histological subtypes and many molecular aberrations are prevalent within specific sarcomas, very few are therapeutically targeted. Instead of utilizing molecular signatures, first-line sarcoma treatment options are still limited to traditional surgery and chemotherapy, and many of the latter remain largely ineffective and are plagued by disease resistance. Currently, the mechanism of sarcoma oncogenesis remains largely unknown, thus necessitating a better understanding of pathogenesis. Although substantial progress has not occurred with molecularly targeted therapies over the past 30 years, increased knowledge about sarcoma biology could lead to new and more effective treatment strategies to move the field forward. Here, we discuss biological advances in the core molecular determinants in some of the most common soft-tissue sarcomas – liposarcoma, angiosarcoma, leiomyosarcoma, rhabdomyosarcoma, Ewing’s sarcoma, and synovial sarcoma – with an emphasis on emerging genomic and molecular pathway targets and immunotherapeutic treatment strategies to combat this confounding disease. PMID:29785138

  16. Advancements in the critical care management of status epilepticus.

    PubMed

    Bauerschmidt, Andrew; Martin, Andrew; Claassen, Jan

    2017-04-01

    Status epilepticus has a high morbidity and mortality. There are little definitive data to guide management; however, new recent data continue to improve understanding of management options of status epilepticus. This review examines recent advancements regarding the critical care management of status epilepticus. Recent studies support the initial treatment of status epilepticus with early and aggressive benzodiazepine dosing. There remains a lack of prospective randomized controlled trials comparing different treatment regimens. Recent data support further study of intravenous lacosamide as an urgent-control therapy, and ketamine and clobazam for refractory status epilepticus. Recent data support the use of continuous EEG to help guide treatment for all patients with refractory status epilepticus and to better understand epileptic activity that falls on the ictal-interictal continuum. Recent data also improve our understanding of the relationship between periodic epileptic activity and brain injury. Many treatments are available for status epilepticus and there are much new data guiding the use of specific agents. However, there continues to be a lack of prospective data supporting specific regimens, particularly in cases of refractory status epilepticus.

  17. A new apatinib microcrystal formulation enhances the effect of radiofrequency ablation treatment on hepatocellular carcinoma.

    PubMed

    Xie, Hui; Tian, Shengtao; Yu, Haipeng; Yang, Xueling; Liu, Jia; Wang, Huaming; Feng, Fan; Guo, Zhi

    2018-01-01

    Radiofrequency ablation (RFA) is the foremost treatment option for advanced hepatocellular carcinoma (HCC), however, rapid and aggressive recurrence of HCC often occurs after RFA due to epithelial-mesenchymal transition process. Although combination of RFA with sorafenib, a molecular targeted agent, could attenuate the recurrence of HCC, application of this molecular targeted agent poses a heavy medical burden and oral administration of sorafenib also brings severe side effects. In this study, we prepared an apatinib microcrystal formulation (Apa-MS) that sustainably releases apatinib, a novel molecular targeted agent, for advanced HCC treatment. We injected apatinib solution or Apa-MS into subcutaneous HCC tumors. It was found that Apa-MS exhibited slow apatinib release in vivo and in turn inhibited the epithelial-mesenchymal transition of HCC cells for extended time. Moreover, in rodent HCC model, Apa-MS enhanced the antitumor effect of RFA treatment. Based on these results, we conclude that Apa-MS, a slow releasing system of apatinib, allows apatinib to remain effective in tumor tissues for a long time and could enhance the antitumor effect of RFA on HCC.

  18. Alcohol addiction - the safety of available approved treatment options.

    PubMed

    Antonelli, Mariangela; Ferrulli, Anna; Sestito, Luisa; Vassallo, Gabriele A; Tarli, Claudia; Mosoni, Carolina; Rando, Maria M; Mirijello, Antonio; Gasbarrini, Antonio; Addolorato, Giovanni

    2018-02-01

    Alcohol Use Disorders (AUD) is a leading cause of mortality and morbidity worldwide. At present disulfiram, naltrexone and acamprosate are approved for the treatment of AUD in U.S. and Europe. Nalmefene is approved in Europe and sodium oxybate is approved in Italy and Austria only. Baclofen received a 'temporary recommendation for use' in France. Areas covered: The safety of the above mentioned medications on liver, digestive system, kidney function, nervous system, pregnancy and lactation and their possible side effects are described and discussed. Expert opinion: Mechanism of action and metabolism of these drugs as well as patients' clinical characteristics can affect the safety of treatment. All approved medications are valid tools for the treatment of AUD in patients without advanced liver disease. For some drugs, attention should be paid to patients with renal failure and medications may be used with caution, adjusting the dosage according to kidney function. In patients with AUD and advanced liver disease, at present only baclofen has been formally tested in randomized controlled trials showing its safety in this population.

  19. Review of differential diagnosis and management of spasmodic dysphonia.

    PubMed

    Whurr, Renata; Lorch, Marjorie

    2016-06-01

    The recent literature on spasmodic dysphonia is reviewed with regard to pathogenesis, differential diagnosis, treatment options, audits, and current methods of management. Advances in technology have enabled clinicians to better understand the connection between brain and laryngeal function and dysfunction. Refinements in imaging and genetic investigation techniques have led to advances in the understanding of the underlying mechanism of this neurolaryngeal disorder. Development of diagnostic assessment tools and measures of quality of life hold the potential to improve treatment and care. Fifty articles published between 2014 and 2015 were selected for this review. The sources were drawn from several clinical specialties: 54% come under the scope of laryngology, 32% from neurology, and 14% from other areas. It remains poorly understood, misdiagnosed, and underdiagnosed. Its identification, diagnosis, treatment selection, and coordination of care require an expert specialist multidisciplinary team. More training is required to help people who have this chronic and psychosocially disabling voice disorder, which impinges on all aspects of their lives. Spasmodic dysphonia is now classified as a 'rare' disease in the United States. This designation will assist in international standards of diagnosis, assessment, treatment, and management.

  20. 78 FR 77181 - Self-Regulatory Organizations; The Options Clearing Corporation; Advance Notice Concerning the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-20

    ... finding or (ii) as to which the self-regulatory organization consents, the Commission will: (A) By order... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-71083; File No. SR-OCC-2013-807] Self-Regulatory Organizations; The Options Clearing Corporation; Advance Notice Concerning the Governance...

  1. Advances and Future Directions in the Treatment of Hepatocellular Carcinoma

    PubMed Central

    Gosalia, Ashil J.; Martin, Paul

    2017-01-01

    Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Liver transplant is considered the gold standard for curative therapy for HCC when patients are not candidates for surgical resection or ablation. Because a subset of patients with HCC have a survival rate with liver transplantation that is comparable to that of cirrhotic patients without tumors, the organ allocation system allows for increased priority for transplant in potential recipients within the Milan criteria. With the recent change in the Model for End-Stage Liver Disease exception point allocation, patients with HCC will now need to wait at least 6 months before being awarded extra points. This extension leads to increased time on the transplant waiting list and underscores the importance of locoregional therapy to contain the tumor burden. Fortunately, there has been significant progress in therapy for HCC in the past few decades, namely due to advances in interventional radiology, radiotherapy, and expanded surgical and transplant criteria. Recent advances in immunotherapy also provide promising options for patients who are not candidates for other therapies. This article highlights the major therapeutic options for HCC, including surgical resection, liver transplant, thermal and nonthermal ablation, chemoembolization, radiotherapy, and systemic chemotherapy, as well as discusses the evidence supporting these approaches. PMID:28867968

  2. Impact of Duodopa on Quality of Life in Advanced Parkinson's Disease: A UK Case Series

    PubMed Central

    Foltynie, T.; Magee, C.; James, C.; Webster, G. J. M.; Lees, A. J.; Limousin, P.

    2013-01-01

    Treatment options in advanced Parkinson's disease (PD) include subcutaneous apomorphine, pallidal or subthalamic nucleus Deep Brain Stimulation (DBS), or levodopa/carbidopa intestinal gel (LCIG/Duodopa). In this study, we describe the outcome of 12 PD patients with PD related complications started on LCIG, with respect to their quality of life measured by a disease specific validated scale—the PDQ39, together with diaries recording time spent “On,” “Off,” “Dyskinetic,” or “Asleep.” At the time of latest follow up, improvements were observed in both the PDQ39 Summary index as well as diary reports of PD symptom control following introduction of LCIG, supporting its use in well selected patients. The use of a trial period of LCIG via naso-jejunal administration allows objective evaluation of improvement in PD symptom control in advance of the placement of the more invasive percutaneous jejunostomy procedure. The decision to embark on LCIG, apomorphine or DBS should be supported by input from centres with experience of all 3 approaches. Since LCIG is an expensive option, development of the most appropriate future commissioning of this therapy in the absence of Class 1 evidence requires careful scrutiny of the outcomes of its use in a broad range of published series. PMID:23476888

  3. Contemporary management of voice and swallowing disorders in patients with advanced lung cancer.

    PubMed

    Brady, Grainne C; Carding, Paul N; Bhosle, Jaishree; Roe, Justin W G

    2015-06-01

    Advanced lung cancer can cause changes to swallowing and communication function. Direct tumour invasion, dyspnoea and deconditioning can all impact on swallowing function and communication. Cancer treatment, if administered, may cause or compound symptoms. In this study, the nature of swallowing and communication difficulties in patients with advanced lung cancer will be discussed, and management options including medical management, speech and language therapy (SLT) intervention, and surgical interventions will be considered. Advanced lung cancer can result in voice and swallowing difficulties, which can increase symptom burden and significantly impact on quality of life (QOL). There is a growing evidence base to support the use of injection laryngoplasty under local anaesthetic to offer immediate improvement in voice, swallowing and overall QOL. There is limited literature on the nature and extent of voice and swallowing impairment in patients with lung cancer. Well designed studies with robust and sensitive multidimensional dysphagia and dysphonia assessments are required. Outcome studies examining interventions with clearly defined treatment goals are required. These studies should include both functional and patient-reported outcome measures to develop the evidence base and to ensure that interventions are both timely and appropriate.

  4. Head and Neck Cancer: An Overview

    PubMed Central

    Stepnick, David; Gilpin, David

    2010-01-01

    Ablative surgery for malignancies of the upper aerodigestive tract is the most common reason why the reconstructive surgeon is called upon to reconstruct adult head and neck defects. An understanding of the pathophysiology and treatment of head and neck malignancy is vital to the reconstructive surgeon so that restoration of both form and function can be achieved. It is important to understand the behavior of cancers of each head and neck subsite, as staging and ultimately the treatment of tumors from each subsite is different. Historically, the standard treatment of head and neck cancer was surgery and/or primary radiation therapy with surgical salvage for failure. Beginning in the 1980s, advances in chemotherapy and concurrent delivery with radiation offered new options to standard surgical therapy. Over the past two decades, the concept of organ preservation using chemotherapy together with radiation therapy has been definitively established. Yet, even with the strides made over these two decades with chemoradiation, surgical treatment of head and neck cancer and reconstruction thereof will be an important treatment option for the foreseeable future. Therefore, the relationship between the extirpative and reconstructive surgeon is vital, and a clear understanding of the biology and behavior of head and neck malignancy is crucial to successful patient outcomes. PMID:22550431

  5. Gene therapy in an era of emerging treatment options for hemophilia B.

    PubMed

    Monahan, P E

    2015-06-01

    Factor IX deficiency (hemophilia B) is less common than factor VIII deficiency (hemophilia A), and innovations in therapy for hemophilia B have generally lagged behind those for hemophilia A. Recently, the first sustained correction of the hemophilia bleeding phenotype by clotting factor gene therapy has been described using recombinant adeno-associated virus (AAV) to deliver factor IX. Despite this success, many individuals with hemophilia B, including children, men with active hepatitis, and individuals who have pre-existing natural immunity to AAV, are not eligible for the current iteration of hemophilia B gene therapy. In addition, recent advances in recombinant factor IX protein engineering have led some hemophilia treaters to reconsider the urgency of genetic cure. Current clinical and preclinical approaches to advancing AAV-based and alternative approaches to factor IX gene therapy are considered in the context of current demographics and treatment of the hemophilia B population. © 2015 International Society on Thrombosis and Haemostasis.

  6. Advances in the management of venous thromboembolism.

    PubMed

    Schulman, Sam

    2012-09-01

    The past decade has witnessed important advances in the diagnosis and treatment of venous thromboembolism with excellent opportunities to apply evidence-based medicine for many of the steps in the management of the disease. This review discusses the clinical prediction rules that should be used to reduce utilization of imaging diagnosis for deep vein thrombosis or pulmonary embolism and the risk stratification for thrombolytic therapy or outpatient management of pulmonary embolism. The treatment options have increased and include low-molecular-weight heparin (LMWH), intravenous or subcutaneous unfractionated heparin - the latter either monitored or not monitored, fondaparinux and rivaroxaban for the initial phase. Thereafter, vitamin K antagonists (VKAs), LMWH, oral factor Xa or thrombin inhibitors are or will soon become available. The VKAs have been subjected to many randomised trial addressing the initiation, intensity, monitoring and self-management. Extended anticoagulation and the selection for that is finally reviewed. Copyright © 2012. Published by Elsevier Ltd.

  7. The modified Altemeier procedure for a loop colostomy prolapse.

    PubMed

    Watanabe, Makoto; Murakami, Masahiko; Ozawa, Yoshiaki; Uchida, Marie; Yamazaki, Kimiyasu; Fujimori, Akira; Otsuka, Koji; Aoki, Takeshi

    2015-11-01

    Loop colostomy prolapse is associated with an impaired quality of life. Surgical treatment may sometimes be required for cases that cannot be closed by colon colostomy because of high-risk morbidities or advanced disease. We applied the Altimeter operation for patients with transverse loop colostomy. The Altemeier operation is therefore indicated for rectal prolapse. This technique involves a simple operation, which includes a circumferential incision through the full thickness of the outer and inner cylinder of the prolapsed limb, without incising the abdominal wall, and anastomosis with sutures using absorbable thread. We performed the Altemeier operation for three cases of loop stomal prolapse. Those patients demonstrated no postoperative complications (including obstruction, prolapse recurrence, or hernia). Our findings suggest that this procedure is useful as an optional surgical treatment for cases of transverse loop colostomy prolapse as a permanent measure in patients with high-risk morbidities or advanced disease.

  8. The Role of Interventional Radiology in the Management of Deep Venous Thrombosis: Advanced Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    O'Sullivan, Gerard J., E-mail: gerard.osullivan2@hse.ie

    2011-06-15

    Deep vein thrombosis (DVT) is often managed with a health care pathway that funnels patients to anticoagulation therapy alone. This 'usual treatment' is designed to stop propagation and embolisation of venous thrombus but not remove it. Surgical thrombectomy was once the only option in severe cases in which limbs were threatened, but thrombus removal is no longer restricted to emergency cases. Interventional radiologists are now using advanced endovascular techniques to achieve thrombus removal in a minimally invasive manner in a very short treatment time, thereby quickly restoring patency, relieving acute symptoms, and potentially limiting the subsequent development of postthrombotic syndromemore » when followed with anticoagulation and compression regimens. This article provides an overview of the interventions available for treating DVT. One of the newer 'single-session' techniques is isolated pharmacomechanical thrombolysis, which is described here in detail with supporting cases.« less

  9. Why calpain inhibitors are interesting leading compounds to search for new therapeutic options to treat leishmaniasis?

    PubMed

    Ennes-Vidal, Vitor; Menna-Barreto, Rubem Figueiredo Sadock; Branquinha, Marta Helena; Dos Santos, André Luis Souza; D'Avila-Levy, Claudia Masini

    2017-02-01

    Leishmaniasis is a neglected disease, which needs improvements in drug development, mainly due to the toxicity, parasite resistance and low compliance of patients to treatment. Therefore, the development of new chemotherapeutic compounds is an urgent need. This opinion article will briefly highlight the feasible use of calpain inhibitors as leading compounds to search for new therapeutic options to treat leishmaniasis. The milestone of this approach is to take advantage on the myriad of inhibitors developed against calpains, some of which are in advanced clinical trials. The deregulated activity of these enzymes is associated with several pathologies, such as strokes, diabetes and Parkinson's disease, to name a few. In Leishmania, calpain upregulation has been associated to drug resistance and virulence. Whereas the difficulties in developing new drugs for neglected diseases are more economical than biotechnological, repurposing approach with compounds already approved for clinical use by the regulatory agencies can be an interesting shortcut to a successful chemotherapeutic treatment for leishmaniasis.

  10. Investigation of Severe Craniomaxillofacial Battle Injuries Sustained by U.S. Service Members: A Case Series

    PubMed Central

    Brown Baer, Pamela R.; Wenke, Joseph C.; Thomas, Steven J.; Hale, Colonel Robert G.

    2012-01-01

    This case series describes craniomaxillofacial battle injuries, currently available surgical techniques, and the compromised outcomes of four service members who sustained severe craniomaxillofacial battle injuries in Iraq or Afghanistan. Demographic information, diagnostic evaluation, surgical procedures, and outcomes were collected and detailed with a follow-up of over 2 years. Reconstructive efforts with advanced, multidisciplinary, and multiple revision procedures were indicated; the full scope of conventional surgical options and resources were utilized. Patients experienced surgical complications, including postoperative wound dehiscence, infection, flap failure, inadequate mandibular healing, and failure of fixation. These complications required multiple revisions and salvage interventions. In addition, facial burns complicated reconstructive efforts by delaying treatment, decreasing surgical options, and increasing procedural numbers. All patients, despite multiple surgeries, continue to have functional and aesthetic deficits as a result of their injuries. Currently, no conventional treatments are available to satisfactorily reconstruct the face severely ravaged by explosive devices to an acceptable level, much less to natural form and function. PMID:24294409

  11. The potential for emerging therapeutic options for Clostridium difficile infection

    PubMed Central

    Mathur, Harsh; Rea, Mary C; Cotter, Paul D; Ross, R Paul; Hill, Colin

    2014-01-01

    Clostridium difficile is mainly a nosocomial pathogen and is a significant cause of antibiotic-associated diarrhea. It is also implicated in the majority of cases of pseudomembranous colitis. Recently, advancements in next generation sequencing technology (NGS) have highlighted the extent of damage to the gut microbiota caused by broad-spectrum antibiotics, often resulting in C. difficile infection (CDI). Currently the treatment of choice for CDI involves the use of metronidazole and vancomycin. However, recurrence and relapse of CDI, even after rounds of metronidazole/vancomycin administration is a problem that must be addressed. The efficacy of alternative antibiotics such as fidaxomicin, rifaximin, nitazoxanide, ramoplanin and tigecycline, as well as faecal microbiota transplantation has been assessed and some have yielded positive outcomes against C. difficile. Some bacteriocins have also shown promising effects against C. difficile in recent years. In light of this, the potential for emerging treatment options and efficacy of anti-C. difficile vaccines are discussed in this review. PMID:25564777

  12. Radiotherapy for locally advanced resectable T3-T4 laryngeal cancer-does laryngeal preservation strategy compromise survival?

    PubMed

    Yamazaki, Hideya; Suzuki, Gen; Nakamura, Satoaki; Hirano, Shigeru; Yoshida, Ken; Konishi, Koji; Teshima, Teruki; Ogawa, Kazuhiko

    2018-01-01

    With the advancement of chemotherapy, a laryngeal preservation (LP) strategy was explored with the aim of improving maintenance of quality of life. Induction chemotherapy (ICT) following radiotherapy (RT) was considered a viable option because of its high initial response rate without hampering of overall survival (OS). Subsequently, concurrent chemoradiotherapy (CCRT) using CDDP became the standard of care for LP, showing the best LP ratio. For enhancing treatment intensity, ICT with taxan + CDDP + 5-FU (TPF-ICT) followed by RT showed superiority over ICT with CDDP + 5-FU (PF-ICT) followed by RT. Given that almost all randomized controlled trials investigating ICT include not only operable (endpoint, LP) but also inoperable (endpoint, OS) cases, physicians are faced with a dilemma regarding application in daily practice. In addition, increased treatment intensity causes augmentation of adverse events, which might reduce compliance. Thereafter, cetuximab, an effective drug with fewer adverse effects [bioradiotherapy (BRT)], emerged as another option. However, little evidence has confirmed its superiority over RT (or CCRT) in laryngeal cancer subpopulations. In spite of these developments, the OS of patients with laryngeal cancer has not improved for several decades. In fact, several studies indicated a decrease in OS during the 1990s, probably due to overuse of CCRT. Fortunately, the latter was not the case in most institutions. Currently, no other treatment has better OS than surgery. The eligibility criteria for LP and/or surgery largely depend upon the available expertise and experience, which differ from one institution to another. Therefore, a multidisciplinary team is required for the treatment of LP. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  13. Energy-Based Facial Rejuvenation: Advances in Diagnosis and Treatment.

    PubMed

    Britt, Christopher J; Marcus, Benjamin

    2017-01-01

    The market for nonsurgical, energy-based facial rejuvenation techniques has increased exponentially since lasers were first used for skin rejuvenation in 1983. Advances in this area have led to a wide range of products that require the modern facial plastic surgeon to have a large repertoire of knowledge. To serve as a guide for current trends in the development of technology, applications, and outcomes of laser and laser-related technology over the past 5 years. We performed a review of PubMed from January 1, 2011, to March 1, 2016, and focused on randomized clinical trials, meta-analyses, systematic reviews, and clinical practice guidelines including case control, case studies and case reports when necessary, and included 14 articles we deemed landmark articles before 2011. Three broad categories of technology are leading non-energy-based rejuvenation technology: lasers, light therapy, and non-laser-based thermal tightening devices. Laser light therapy has continued to diversify with the use of ablative and nonablative resurfacing technologies, fractionated lasers, and their combined use. Light therapy has developed for use in combination with other technologies or stand alone. Finally, thermally based nonlaser skin-tightening devices, such as radiofrequency (RF) and intense focused ultrasonography (IFUS), are evolving technologies that have changed rapidly over the past 5 years. Improvements in safety and efficacy for energy-based treatment have expanded the patient base considering these therapies viable options. With a wide variety of options, the modern facial plastic surgeon can have a frank discussion with the patient regarding nonsurgical techniques that were never before available. Many of these patients can now derive benefit from treatments requiring significantly less downtime than before while the clinician can augment the treatment to maximize benefit to fit the patient's time schedule.

  14. The New Era of Interferon-Free Treatment of Chronic Hepatitis C

    PubMed Central

    Solbach, Philipp; Wedemeyer, Heiner

    2015-01-01

    Summary Background Within the development and approval of several new direct-acting antivirals (DAA) against hepatitis C virus (HCV), a new era of hepatitis C therapy has begun. Even more treatment options are likely to become available during the next 1-2 years. Methods A summary of the current phase II and III trials investigating DAA and a review of the recent HCV guidelines was conducted. Results With the development of new potent DAA and the approval of different DAA combinations, cure rates of HCV infection of >90% are achievable for almost all HCV genotypes and stages of liver disease. Currently available DAA target different steps in the HCV replication cycle, in particular the NS3/4A protease, the NS5B polymerase, and the NS5A replication complex. Treatment duration varies between 8 and 24 weeks depending on the stage of fibrosis, prior treatment, HCV viral load, and HCV genotype. Ribavirin is required only for some treatment regimens and may be particularly beneficial in patients with cirrhosis. DAA resistance influences treatment outcome only marginally; thus, drug resistance testing is not routinely recommended before treatment. In the case of treatment failure, however, resistance testing should be performed before re-treatment with other DAA is initiated. Conclusion With the new, almost side effect-free DAA treatment options chronic HCV infection became a curable disease. The clinical benefit of DAA combination therapies in patients with advanced cirrhosis and the effects on incidence rates of hepatocellular carcinoma remain to be determined. PMID:26557839

  15. Intra-operative hemodialysis during liver transplantation: an expanded role of the nephrology nurse.

    PubMed

    Henson, Angela; Carpenter, Sally

    2010-01-01

    Hemodialysis is widely acknowledged as a treatment option to stabilize acute medical conditions where biochemistry management is paramount. One of the most challenging situations is during liver transplantation, when patients with moderate renal dysfunction are likely to become acutely acidotic. For nephrology nurses, this extended role requires increased knowledge, advanced skills, and a high level of communication with unfamiliar team members. With appropriate procedures and a supportive environment, delivering such a service is feasible.

  16. Chronic obstructive pulmonary disease: More than meets the eye.

    PubMed

    Hatipoğlu, Umur

    2018-01-01

    Chronic obstructive pulmonary disease (COPD) is a major health problem which had not received the attention commensurate with the magnitude of its global burden. This is finally changing with the help of a vibrant community of health-care professionals, public officials, and academic researchers. Advances in characterization of the disease, treatment options, imaging modalities, and better understanding of the comorbidities promise to revolutionize how the disease is managed. COPD should no longer augur despair among physicians and patients.

  17. Immunotherapy for liver tumors: present status and future prospects

    PubMed Central

    Matar, Pablo; Alaniz, Laura; Rozados, Viviana; Aquino, Jorge B; Malvicini, Mariana; Atorrasagasti, Catalina; Gidekel, Manuel; Silva, Marcelo; Scharovsky, O Graciela; Mazzolini, Guillermo

    2009-01-01

    Increasing evidence suggests that immune responses are involved in the control of cancer and that the immune system can be manipulated in different ways to recognize and attack tumors. Progress in immune-based strategies has opened new therapeutic avenues using a number of techniques destined to eliminate malignant cells. In the present review, we overview current knowledge on the importance, successes and difficulties of immunotherapy in liver tumors, including preclinical data available in animal models and information from clinical trials carried out during the lasts years. This review shows that new options for the treatment of advanced liver tumors are urgently needed and that there is a ground for future advances in the field. PMID:19272130

  18. Technology-aided leisure and communication: Opportunities for persons with advanced Parkinson's disease.

    PubMed

    Lancioni, Giulio; Singh, Nirbhay; O'Reilly, Mark; Sigafoos, Jeff; D'Amico, Fiora; Sasanelli, Giovanni; Denitto, Floriana; Lang, Russell

    2016-12-01

    This study investigated whether simple technology-aided programs could be used to promote leisure and communication engagement in three persons with advanced Parkinson's disease. The programs included music and video options, which were combined with (a) text messaging and telephone calls for the first participant, (b) verbal statements/requests, text messaging, and reading for the second participant, and (c) verbal statements/requests and prayers for the third participant. The participants could activate those options via hand movement or vocal emission and specific microswitches. All three participants were successful in activating the options available. The mean cumulative frequencies of option activations were about five per 15-min session for the first two participants and about four per 10-min session for the third participant. The results were considered encouraging and relevant given the limited amount of evidence available on helping persons with advanced Parkinson's disease with leisure and communication.

  19. Should EGFR mutations be tested in advanced lung squamous cell carcinomas to guide frontline treatment?

    PubMed

    Chiu, Chao-Hua; Chou, Teh-Ying; Chiang, Chi-Lu; Tsai, Chun-Ming

    2014-10-01

    There is no argument over using epidermal growth factor receptor (EGFR) mutation status to guide the frontline treatment for advanced lung adenocarcinoma (LADC); however, the role of the testing in lung squamous cell carcinoma (LSQC) remains controversial. Currently, the guidelines/consensus statements regarding EGFR mutation testing in LSQC are not consistent among different oncology societies. American Society of Clinical Oncology recommends performing EGFR mutation testing in all patients; European Society for Medical Oncology, College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology, and National Comprehensive Cancer Network suggest for some selected group. EGFR mutation is rarely found in LSQC; however, more importantly, it is not a valid predictive biomarker for EGFR tyrosine kinase inhibitors (EGFR-TKI) in LSQC as it has been shown in LADC. Available data showed that the response rate and progression-free survival in EGFR mutant LSQC patients treated with EGFR-TKI are not better than that observed in patients treated with platinum-doublet chemotherapy in the first-line setting. Therefore, in contrast to advanced LADC, EGFR mutation testing may not be necessarily performed upfront in advanced LSQC because not only the mutation rate is low, but also the predictive value is insufficient. For LSQC patients with known sensitizing-EGFR mutations, both conventional chemotherapy and EGFR-TKI are acceptable frontline treatment options.

  20. Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial.

    PubMed

    Migden, Michael R; Guminski, Alexander; Gutzmer, Ralf; Dirix, Luc; Lewis, Karl D; Combemale, Patrick; Herd, Robert M; Kudchadkar, Ragini; Trefzer, Uwe; Gogov, Sven; Pallaud, Celine; Yi, Tingting; Mone, Manisha; Kaatz, Martin; Loquai, Carmen; Stratigos, Alexander J; Schulze, Hans-Joachim; Plummer, Ruth; Chang, Anne Lynn S; Cornélis, Frank; Lear, John T; Sellami, Dalila; Dummer, Reinhard

    2015-06-01

    Patients with advanced basal cell carcinoma have limited treatment options. Hedgehog pathway signalling is aberrantly activated in around 95% of tumours. We assessed the antitumour activity of sonidegib, a Hedgehog signalling inhibitor, in patients with advanced basal cell carcinoma. BOLT is an ongoing multicentre, randomised, double-blind, phase 2 trial. Eligible patients had locally advanced basal cell carcinoma not amenable to curative surgery or radiation or metastatic basal cell carcinoma. Patients were randomised via an automated system in a 1:2 ratio to receive 200 mg or 800 mg oral sonidegib daily, stratified by disease, histological subtype, and geographical region. The primary endpoint was the proportion of patients who achieved an objective response, assessed in the primary efficacy analysis population (patients with fully assessable locally advanced disease and all those with metastatic disease) with data collected up to 6 months after randomisation of the last patient. This trial is registered with ClinicalTrials.gov, number NCT01327053. Between July 20, 2011, and Jan 10, 2013, we enrolled 230 patients, 79 in the 200 mg sonidegib group, and 151 in the 800 mg sonidegib group. Median follow-up was 13·9 months (IQR 10·1-17·3). In the primary efficacy analysis population, 20 (36%, 95% CI 24-50) of 55 patients receiving 200 mg sonidegib and 39 (34%, 25-43) of 116 receiving 800 mg sonidegib achieved an objective response. In the 200 mg sonidegib group, 18 (43%, 95% CI 28-59) patients who achieved an objective response, as assessed by central review, were noted among the 42 with locally advanced basal cell carcinoma and two (15%, 2-45) among the 13 with metastatic disease. In the 800 mg group, 35 (38%, 95% CI 28-48) of 93 patients with locally advanced disease had an objective response, as assessed by central review, as did four (17%, 5-39) of 23 with metastatic disease. Fewer adverse events leading to dose interruptions or reductions (25 [32%] of 79 patients vs 90 [60%] of 150) or treatment discontinuation (17 [22%] vs 54 [36%]) occurred in patients in the 200 mg group than in the 800 mg group. The most common grade 3-4 adverse events were raised creatine kinase (five [6%] in the 200 mg group vs 19 [13%] in the 800 mg group) and lipase concentration (four [5%] vs eight [5%]). Serious adverse events occurred in 11 (14%) of 79 patients in the 200 mg group and 45 (30%) of 150 patients in the 800 mg group. The benefit-to-risk profile of 200 mg sonidegib might offer a new treatment option for patients with advanced basal cell carcinoma, a population that is difficult to treat. Novartis Pharmaceuticals Corporation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Alectinib: a review of its use in advanced ALK-rearranged non-small cell lung cancer.

    PubMed

    McKeage, Kate

    2015-01-01

    Alectinib (Alecensa(®)) is a second-generation, orally active, potent and highly selective inhibitor of anaplastic lymphoma kinase (ALK). Alectinib is approved for the treatment of ALK fusion-gene positive, unresectable, advanced or recurrent non-small cell lung cancer (NSCLC) in Japan, where it has been given orphan drug designation. Approval was based on a phase 1-2 study in ALK inhibitor-naive patients with ALK-rearranged advanced NSCLC who received twice-daily alectinib 300 mg. In the phase 2 portion, 93.5 % of patients achieved an objective response. Treatment response was rapid, with a partial response achieved in two-thirds of patients within 3 weeks (cycle 1). Patient follow-up is ongoing, and after approximately 2 years, 19.6 % of patients had achieved a complete response, and the 2-year progression-free survival rate is 76 %. During treatment with alectinib (median follow-up approximately 8 months), there was no progression of CNS lesions among patients with known CNS metastases at baseline (although prior radiation therapy may have confounded results). In preclinical models, alectinib was active against most ALK fusion-gene mutations related to crizotinib resistance, and preliminary results from clinical trials indicate efficacy in crizotinib-refractory NSCLC. Alectinib was generally well tolerated in clinical trials, and there were no treatment-related grade 4 adverse events or deaths. The most common grade 3 treatment-related adverse events were decreased neutrophil counts and increased creatinine phosphokinase. While more data are needed to confirm the efficacy of alectinib and to evaluate its activity in crizotinib-resistant disease, the drug provides a very promising option for the treatment of ALK-rearranged advanced NSCLC.

  2. Treatment decision-making processes in the systemic treatment of ovarian cancer: review of the scientific evidence.

    PubMed

    Luketina, Hrvoje; Fotopoulou, Christina; Luketina, Ruzica-Rosalia; Pilger, Adak; Sehouli, Jalid

    2012-09-01

    The systemic treatment of epithelial ovarian cancer (OC) is one of the cornerstones in the multimodal management of advanced OC in both primary and recurrent stages of this disease. In most situations various treatment options are available but only few data exists about the treatment decision-making process. Therefore, we conducted a review of the current literature regarding the decision-making process concerning the systemic therapy in patients with advanced ovarian cancer. The electronic database MEDLINE (PubMed) was systematically reviewed for studies that evaluate the treatment decision-making processes in patients with advanced OC. The PubMed database was searched in detail for all titles and abstracts of potentially relevant studies published between 1995 and 2011. An initial search identified 15 potentially relevant studies, but only seven met all inclusion criteria. Factors that influence treatment decisions in patients with OC include not only rational arguments and medical reasons, but also individual attitudes, fears, existential questions, various projections resulting from the physician patient relationship and the social environment. The physician's personal experience with OC treatment seems to be an important factor, followed by previous personal experience with medical issues, and the fear of side-effects and future metastases. Family and self-support organisations also seem to play a significant role in the treatment decision-making process. This review underlines the need for more research activities to explore the treatment decision-making process to enable the best individual support for patients in treatment decision-making. It is a challenge for clinicians to determine the individual information needs of women with OC and to involve them during the decision-making process to the extent they wish.

  3. Travel and Tourism Module. An Advanced-Level Option For Distribution and Marketing.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Bureau of Occupational Education Curriculum Development.

    Intended as an advanced option for distributive education students in the twelfth grade, this travel and tourism module is designed to cover a minimum of ten weeks or a maximum of twenty weeks. Introductory material includes information on employment demands, administrative considerations, course format, teaching suggestions, expected outcomes,…

  4. Vocational Options for Deaf-Blind Youth Through Community-Based Training. Project ADVANCE.

    ERIC Educational Resources Information Center

    McGinnity, Betsy L.

    Project ADVANCE currently provides vocational training to 26 deaf-blind adolescents and young adults attending Perkins School for the Blind in Watertown, Massachusetts. The project has developed community work sites in four different vocational options: (1) competitive employment, (2) a student operated small business, (3) sheltered enclave within…

  5. New Promising Strategies in Oncofertility

    PubMed Central

    Hudson, Janella N.; Stanley, Nathanael B.; Nahata, Leena; Bowman-Curci, Meghan; Quinn, Gwendolyn P.

    2017-01-01

    Introduction Approximately 70,000 adolescent and young adults (AYA) are diagnosed with cancer each year. While advancements in treatment have led to improved prognosis and survival for patients, these same treatments can adversely affect AYA reproductive capacity. Localized treatments such as surgery and radiation therapy may affect fertility by removing or damaging reproductive organs, and systemic therapies such as chemotherapy can be toxic to gonads, (ovaries and testicles), thus affecting fertility and/or endocrine function. This can be traumatic for AYA with cancer as survivors often express desire to have genetic children and report feelings of regret or depression as a result of infertility caused by cancer treatments. Areas Covered Emerging technologies in the field of assisted reproductive technology offer new promise for preserving the reproductive capacity of AYA cancer patients prior to treatment as well as providing alternatives for survivors. The following review revisits contemporary approaches to fertility preservation as well newly developing technologies. Expert Commentary There are several advances in ART that hold promise for patients and survivors. However there are challenges that inhibit uptake including poor communication between providers and patients about risks and fertility preservation options; high costs; and lack of insurance coverage for fertility preservation services. PMID:28959743

  6. Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer.

    PubMed

    Blair, Hannah A

    2018-05-21

    Atezolizumab (TECENTRIQ™), an immune checkpoint inhibitor, is an immunoglobulin G1 monoclonal antibody that binds to programmed death ligand 1 (PD-L1) and blocks its interactions with programmed death 1 and B7.1 receptors. Atezolizumab is approved as monotherapy in several countries worldwide for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy. Approval was based on its clinical benefit in this setting in the phase II POPLAR and phase III OAK trials. In these studies, atezolizumab significantly prolonged overall survival (OS) relative to docetaxel, regardless of PD-L1 status. Increasing PD-L1 expression was associated with OS improvements. Atezolizumab also demonstrated efficacy in the phase II FIR and BIRCH trials, as assessed by objective response rates (ORRs) in patients with tumours expressing PD-L1. Higher ORRs were seen in patients with high PD-L1 expression. Atezolizumab had an acceptable, manageable tolerability profile, with a low incidence of immune-related adverse events. Therefore, atezolizumab is a valuable treatment option for patients with advanced NSCLC that has progressed during or after chemotherapy.

  7. Laparoscopic splenic hilar lymphadenectomy for advanced gastric cancer.

    PubMed

    Hosogi, Hisahiro; Okabe, Hiroshi; Shinohara, Hisashi; Tsunoda, Shigeru; Hisamori, Shigeo; Sakai, Yoshiharu

    2016-01-01

    Laparoscopic distal gastrectomy has recently become accepted as a surgical option for early gastric cancer in the distal stomach, but laparoscopic total gastrectomy (LTG) has not become widespread because of technical difficulties of esophagojejunal anastomosis and splenic hilar lymphadenectomy. Splenic hilar lymphadenectomy should be employed in the treatment of advanced proximal gastric cancer to complete D2 dissection, but laparoscopically it is technically difficult even for skilled surgeons. Based on the evidence that prophylactic combined resection of spleen in total gastrectomy increased the risk of postoperative morbidity with no survival impact, surgeons have preferred laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPL) for advanced tumors without metastasis to splenic hilar nodes or invasion to the greater curvature of the stomach, and reports with LSPL have been increasing rather than LTG with splenectomy. In this paper, recent reports with laparoscopic splenic hilar lymphadenectomy were reviewed.

  8. Different treatment strategies for highly polluted landfill leachate in developing countries.

    PubMed

    Mahmud, Kashif; Hossain, Md Delwar; Shams, Shahriar

    2012-11-01

    The aim of this research was to determine appropriate treatment technique for effective treatment of heavily polluted landfill leachate. We accomplished several treatment experiments: (i) aerobic biological treatment, (ii) chemical coagulation, (iii) advanced oxidation process (AOP) and (iv) several combined treatment strategies. Efficiency of these treatment procedures were monitored by analysing COD and colour removal. Leachate used for this study was taken from Matuail landfill site at Dhaka city. With extended aeration process which is currently used in Matuail landfill site for leachate treatment, maximum COD and colour removal of 36% and 20%, respectively could be achieved with optimum retention period of 7 days. With optimum aluminium sulphate dose of 15,000 mg/L and pH value of 7.0, maximum COD and colour removals of 34% and 66%, respectively were observed by using chemical coagulation. With optimum pH of 5.0 and optimum dosages of reagents having H(2)O(2)/Fe(2+) molar ratio of 1.3 the highest removal of COD and colour were found 68% and 87%, respectively with sludge production of 55%. Fenton treatment which is an advanced oxidation process was the most successful between these three separate treatment procedures. Among the combined treatment options performed, extended aeration followed by Fenton method was the most suitable one. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Assessing the information desire of patients with advanced cancer by providing information with a decision aid, which is evaluated in a randomized trial: a study protocol.

    PubMed

    Oostendorp, Linda J M; Ottevanger, Petronella B; van der Graaf, Winette T A; Stalmeier, Peep F M

    2011-02-14

    There is a continuing debate on the desirability of informing patients with cancer and thereby involving them in treatment decisions. On the one hand, information uptake may be hampered, and additional stress could be inflicted by involving these patients. On the other hand, even patients with advanced cancer desire information on risks and prognosis. To settle the debate, a decision aid will be developed and presented to patients with advanced disease at the point of decision making. The aid is used to assess the amount of information desired. Factors related to information desire are explored, as well as the ability of the medical oncologist to judge the patient's information desire. The effects of the information on patient well-being are assessed by comparing the decision aid group with a usual care group. This study is a randomized controlled trial of patients with advanced colorectal, breast, or ovarian cancer who have started treatment with first-line palliative chemotherapy. The trial will consist of 100 patients in the decision aid group and 70 patients in the usual care group. To collect complete data of 170 patients, 246 patients will be approached for the study. Patients will complete a baseline questionnaire on sociodemographic data, well-being measures, and psychological measures, believed to predict information desire. The medical oncologist will judge the patient's information desire. After disease progression is diagnosed, the medical oncologist offers the choice between second-line palliative chemotherapy plus best supportive care (BSC) and BSC alone. Randomization will take place to determine whether patients will receive usual care (n = 70) or usual care and the decision aid (n = 100). The aid offers information about the potential risks and benefits of both treatment options, in terms of adverse events, tumour response, and survival. Patients decide for each item whether they desire the information or not. Two follow-up questionnaires will evaluate the effect of the decision aid. This study attempts to settle the debate on the desirability of informing patients with cancer. In contrast to several earlier studies, we will actually deliver information on treatment options to patients at the point of decision making.

  10. Complex Care Options for Patients With Advanced Heart Failure Approaching End of Life.

    PubMed

    Wordingham, Sara E; McIlvennan, Colleen K; Dionne-Odom, J Nicholas; Swetz, Keith M

    2016-02-01

    Care for patients with advanced cardiac disease continues to evolve in a complex milieu of therapeutic options, advanced technological interventions, and efforts at improving patient-centered care and shared decision-making. Despite improvements in quality of life and survival with these interventions, optimal supportive care across the advanced illness trajectory remains diverse and heterogeneous. Herein, we outline challenges in prognostication, communication, and caregiving in advanced heart failure and review the unique needs of patients who experience frequent hospitalizations, require chronic home inotropic support, and who have implantable cardioverter-defibrillators and mechanical circulatory support in situ, to name a few.

  11. Efficacy and safety of ipilimumab 3mg/kg in patients with pretreated, metastatic, mucosal melanoma.

    PubMed

    Del Vecchio, Michele; Di Guardo, Lorenza; Ascierto, Paolo A; Grimaldi, Antonio M; Sileni, Vanna Chiarion; Pigozzo, Jacopo; Ferraresi, Virginia; Nuzzo, Carmen; Rinaldi, Gaetana; Testori, Alessandro; Ferrucci, Pier F; Marchetti, Paolo; De Galitiis, Federica; Queirolo, Paola; Tornari, Elena; Marconcini, Riccardo; Calabrò, Luana; Maio, Michele

    2014-01-01

    Mucosal melanoma is an extremely rare and aggressive malignancy that often remains undetected until it reaches an advanced stage, when effective treatment options are limited. The activity and safety of ipilimumab were assessed in an Expanded Access Programme (EAP) that included patients with metastatic, mucosal melanoma. Ipilimumab was available upon physician request for patients aged ⩾16years with stage III (unresectable) or IV skin, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Patients received ipilimumab 3mg/kg every 3weeks for four doses. Patients with stable disease or an objective response to ipilimumab were eligible for retreatment upon disease progression. Tumour assessments were conducted at baseline and week 12 using immune-related response criteria. Patients were monitored for adverse events (AEs), including immune-related AEs, within 3 to 4days of each scheduled visit. Of 855 patients participating in the EAP in Italy, 71 (8%) had metastatic, mucosal melanoma. With a median follow-up of 21.8months, the response rate was 12% and the immune-related disease control rate was 36%. Median progression-free survival and overall survival were 4.3 and 6.4months, respectively. In total, 34% of patients reported treatment-related AEs of any grade, which were grade 3 or 4 in 9% of patients. AEs were generally manageable as per protocol-specific guidelines. Ipilimumab may be a feasible treatment option in pretreated patients with metastatic mucosal melanoma, and warrants further investigation in prospective clinical trials. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. [Standards, options, and recommendations for initial management of patients with malignant ovarian epithelial tumors].

    PubMed

    Kerbrat, P; Lhommé, C; Fervers, B; Guastalla, J P; Thomas, L; Basuyau, J P; Duvillard, P; Cohen-Solal, C; Dauplat, J; Tournemaine, N

    2000-12-09

    Suprapubic and transvaginal pelvic ultrasound exploration is indicated for suspected ovarian tumor (standard). Diagnosis and search for extension require surgery and pathology examination. Systematic preoperative computed tomography is not recommended (standard). Surgery for cancer of the ovary is a specialized procedure requiring skill in cancer, gynecology, visceral surgery and laparoscopic surgery. If the patient is referred to a specialized center after a primary procedure considered to be inadequate, a new procedure is recommended for staging. Residual tumor volume after the primary procedure has prognostic value. Systematic second look procedures are not recommended for routine practice (standard). For patients with grade IA G1 tumors, there is no indication for complementary treatment (standard). For patients with grade IA G2-3 or clear cell tumors, IB, IC, IIA, there is no standard. no complementary treatment, complementary chemotherapy using platinum, complementary external abdominopelvic radiotherapy. A complementary treatment is recommended for grades IC and IIA. Complementary treatment for grades IIB (no residual tissue), IIC (with residual tissue), III (no residual tissue), is based on: complementary chemotherapy with platinium, complementary external abdominopelvic radiotherapy (options). Complementary treatment for advanced forms (IIB (with residual tissue), IIC (with residual tissue), III (with residual tissue) and IV) is based on polychemotherapy with platinium (standard). platinium combined with paclitaxel (intravenous), platinium combined with cyclophosphamide and/or doxorubicin (intravenous) or intraperitoneal cisplatin combined with cyclophosphamide (intravenous). The chemotherapy work-up includes physical examination, assay of serum markers (particularly CA125) and abdominopelvic computed tomography (proof level B) (standard). Physical examination is recommended for monitoring patients in complete remission with no sign of suspected recurrence (standard). This document was reviewed in April 1977. The working group again validated the Standards, OPTIONS and Recommendations, without modifications in June 1999.

  13. Stem cells and combination therapy for the treatment of traumatic brain injury.

    PubMed

    Dekmak, AmiraSan; Mantash, Sarah; Shaito, Abdullah; Toutonji, Amer; Ramadan, Naify; Ghazale, Hussein; Kassem, Nouhad; Darwish, Hala; Zibara, Kazem

    2018-03-15

    TBI is a nondegenerative, noncongenital insult to the brain from an external mechanical force; for instance a violent blow in a car accident. It is a complex injury with a broad spectrum of symptoms and has become a major cause of death and disability in addition to being a burden on public health and societies worldwide. As such, finding a therapy for TBI has become a major health concern for many countries, which has led to the emergence of many monotherapies that have shown promising effects in animal models of TBI, but have not yet proven any significant efficacy in clinical trials. In this paper, we will review existing and novel TBI treatment options. We will first shed light on the complex pathophysiology and molecular mechanisms of this disorder, understanding of which is a necessity for launching any treatment option. We will then review most of the currently available treatments for TBI including the recent approaches in the field of stem cell therapy as an optimal solution to treat TBI. Therapy using endogenous stem cells will be reviewed, followed by therapies utilizing exogenous stem cells from embryonic, induced pluripotent, mesenchymal, and neural origin. Combination therapy is also discussed as an emergent novel approach to treat TBI. Two approaches are highlighted, an approach concerning growth factors and another using ROCK inhibitors. These approaches are highlighted with regard to their benefits in minimizing the outcomes of TBI. Finally, we focus on the consequent improvements in motor and cognitive functions after stem cell therapy. Overall, this review will cover existing treatment options and recent advancements in TBI therapy, with a focus on the potential application of these strategies as a solution to improve the functional outcomes of TBI. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Balancing risk and benefit for first-line treatment of metastatic colorectal cancer: a graphic communication tool for patients and physicians.

    PubMed

    Sanatani, Michael S; Vincent, Mark D

    2007-01-01

    Advances in the treatment of metastatic colorectal cancer have improved overall survival (OS); however, this might come at the cost of increased toxicity. Health-related quality of life, a significant concern closely related to toxicity and important when discussing palliative therapy, is infrequently assessed and reported in older clinical trials. As the number of tested regimens increases, the question arises on how to best present palliative treatment options. We present a simple way to compare treatment options in terms of potential risks and benefits. The literature was surveyed for reports of first-line systemic chemotherapies for metastatic colorectal cancer. The largest recent reports with detailed toxicity data were selected as representative for a regimen. Toxicity sum of a regimen was calculated as percent occurrences in the study cohort of severe adverse effects: diarrhea, mucositis, neurocutaneous conditions (excluding alopecia), vomiting, and febrile neutropenia. Limitations of toxicity reporting precluded inclusion of other or milder adverse events. Benefits (OS and progression-free survival [PFS]) were plotted graphically as benefit versus toxicity sum. Thirty-four regimens were found. Overall survival, PFS, and toxicity sum ranged from 8.9-24.7 months, 4.9-9.2 months, and 12-70 months, respectively. Weaknesses of our study include omission of some specific toxicities and of symptom control benefit, as well as heterogeneity of trial design and study populations. Furthermore, more recent OS data might reflect the availability of more lines of therapy rather than the effect of the first-line regimen, as comparison with PFS outcomes show. Our comparative tool helps physicians discuss the large number of available options with a patient in order to arrive at the treatment plan most appropriate to the individual and improve informed consent and disclosure, while highlighting limitations in available evidence.

  15. Advances in digital technology and orthodontics: a reference to the Invisalign method.

    PubMed

    Melkos, Aristides B

    2005-05-01

    Increased aesthetic demands during orthodontic treatment resulted in several treatment alternatives. However, the need to avoid conventional fixed orthodontic appliances led, with the use of computer-aided scanning, imaging, and manufacturing technology, to the development of new therapy concepts such as Invisalign. The Invisalign orthodontic technique involves a series of clear removable appliances and has been applied to correct a variety of malocclusions. The Invisalign method is an aesthetic orthodontic option for many patients, but it is suited mainly to adults or adolescents who have a fully erupted dentition and it has its indications and limitations. It handles simple to moderate non-extraction alignments better than mild to moderate extraction cases. The aligners are clear and therefore aesthetically ideal for the patient; they are comfortable to wear and, as they are removable, they provide simplicity of care and better oral hygiene. They also allow the evaluation of treatment options in detail before beginning treatment by using a virtual treatment model. It is also important to point out that this method has some disadvantages, which are associated with patient compliance, limited control over specific tooth movements, and additional documentation time. The Invisalign concept is an aesthetic alternative in orthodontic treatment, with advantages and disadvantages. It can be utilized to treat simple to moderate alignment cases, especially in adults, and serves as an additional part of the armamentarium of the orthodontist.

  16. Cancer vaccines inducing antibody production: more pros than cons.

    PubMed

    Jensen-Jarolim, Erika; Singer, Josef

    2011-09-01

    To date, passive immunotherapy with monoclonal antibodies is a well-established option in clinical oncology. By contrast, anticancer vaccines are less advanced, with the exception of successfully applied prophylactic vaccines against oncogenic virus infections. The creation of therapeutic vaccines is still a great challenge mostly due to the self-nature of tumor antigens. Therapeutic vaccines may be based on patient-specific material including pulsed effector cells, or tumor-associated antigens and derivatives thereof, such as peptides, mimotopes and nucleic acids. The latter represents a more universal approach, which would set an ideal economic framework resulting in broad patient access. In this article we focus on cancer vaccines for antibody production, in particular mimotope vaccines. The collected evidence suggests that they will open up new treatment options in minimal residual disease and early stage disease.

  17. Advances in Imaging and Management Trends of Traumatic Aortic Injuries.

    PubMed

    Nagpal, Prashant; Mullan, Brian F; Sen, Indrani; Saboo, Sachin S; Khandelwal, Ashish

    2017-05-01

    Acute traumatic aortic injury (ATAI) is a life-threatening injury. CT is the imaging tool of choice, and the knowledge of direct and indirect signs of injury, grading system, and current management protocol helps the emergency radiologist to better identify and classify the injury and provide additional details that can impact management options. Newer dual-source CT technology with ultrafast acquisition speed has also influenced the appropriate protocol for imaging in patients with suspected ATAI. This review highlights the imaging protocol in patients with blunt trauma, CT appearance and grading systems of ATAI, management options, and the role of the multidisciplinary team in the management of these patients. We also briefly review the current literature on the definition, treatment, and follow-up protocol in patients with minimal aortic injury.

  18. Stroke and neurodegenerative disorders. 3. Stroke: rehabilitation management.

    PubMed

    Bogey, Ross A; Geis, Carolyn C; Bryant, Phillip R; Moroz, Alex; O'neill, Bryan J

    2004-03-01

    This self-directed learning module highlights common rehabilitation issues in stroke survivors. Topics include spasticity, constraint-induced movement therapy, partial body weight-supported treadmill training, virtual reality training, vestibular retraining, aphasia treatment, and cognitive retraining. It is part of the study chapter on stroke and neurodegenerative disorders in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. (a) To identify and review the treatment options for poststroke spasticity; (b) to review the use of body weight-supported treadmill training in stroke patients; (c) to describe virtual reality training as an adjunct in stroke rehabilitation; (d) to review vestibular rehabilitation; (e) to discuss advances in aphasia treatment; (f) to discuss cognitive retraining; and (g) to provide an update on treatment of neglect syndromes.

  19. The economic evaluation of personalised oncology medicines: ethical challenges.

    PubMed

    Lewis, Jan R R; Lipworth, Wendy L; Kerridge, Ian H; Day, Richard O

    2013-10-07

    Insights into the molecular drivers of cancer are providing opportunities for the development of new targeted treatments and more personalised approaches to cancer management. Drugs targeting mutant epidermal growth factor receptors, such as erlotinib and gefitinib, may provide more effective, safer and better tolerated treatment options compared with chemotherapy among appropriately selected patients with advanced non-small cell lung cancer (NSCLC). First-line access to these newer treatments remains unfunded after several considerations by the Pharmaceutical Benefits Advisory Committee and their assessment that these are not cost-effective treatments. We suggest that there may be evidentiary and ethical challenges associated with the assessment of the cost-effectiveness of personalised oncology medicines in Australia, and that a new approach is needed to determine the value and cost-effectiveness of personalised medicine.

  20. [Treatment of advanced hepatocellular carcinoma : Novel agents and role of local therapy].

    PubMed

    Parisod, Louis; Duran, Rafael; Denys, Alban; Digklia, Antonia

    2017-05-17

    The incidence of hepatocellular carcinoma (HCC) is increasing in Switzerland and its treatment is a challenge. The purpose of this article is to summarize the different therapeutic approaches in the metastatic stage, as well as the perspectives of targeted treatments and immunotherapy. Until recently, the only recognized therapeutic standard for these patients with metastatic CHC was sorafenib, a tyrosine kinase inhibitor. If the patient was to progress under sorafenib, no other recognized therapeutic option was available as second line. We present in this article the recent data on regorafenib, also an inhibitor of tyrosine kinases, the first systemic therapy showing an increase in survival for patients progressing under sorafenib. Then we will discuss promising data and progress made in treatments checkpoints inhibitors and therapies combining local and systematic approaches.

  1. Assessment for advanced fuel cycle options in CANDU

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Morreale, A.C.; Luxat, J.C.; Friedlander, Y.

    2013-07-01

    The possible options for advanced fuel cycles in CANDU reactors including actinide burning options and thorium cycles were explored and are feasible options to increase the efficiency of uranium utilization and help close the fuel cycle. The actinide burning TRUMOX approach uses a mixed oxide fuel of reprocessed transuranic actinides from PWR spent fuel blended with natural uranium in the CANDU-900 reactor. This system reduced actinide content by 35% and decreased natural uranium consumption by 24% over a PWR once through cycle. The thorium cycles evaluated used two CANDU-900 units, a generator and a burner unit along with a drivermore » fuel feedstock. The driver fuels included plutonium reprocessed from PWR, from CANDU and low enriched uranium (LEU). All three cycles were effective options and reduced natural uranium consumption over a PWR once through cycle. The LEU driven system saw the largest reduction with a 94% savings while the plutonium driven cycles achieved 75% savings for PWR and 87% for CANDU. The high neutron economy, online fuelling and flexible compact fuel make the CANDU system an ideal reactor platform for many advanced fuel cycles.« less

  2. A cross-sectional survey comparing a free treatment program for advanced schistosomiasis japonica to a general assistance program.

    PubMed

    Song, Langui; Wu, Xiaoying; Zhang, Beibei; Liu, Jiahua; Ning, An; Wu, Zhongdao

    2017-11-01

    The prevalence and intensity of schistosomiasis has dropped dramatically in China due to an effective integrated control program. However, advanced schistosomiasis is becoming a key challenge on the road to elimination. The aims of this study were to compare the disease condition between advanced cases under the general assistance program (GAP) and free treatment program (FTP) and to determine whether the FTP should be popularized to provide an objective reference for policymakers in China's advanced schistosomiasis control program. One hundred and ninety-four patients with schistosomiasis japonica who were enrolled in the GAP or FTP participated in this study. Little significant difference was observed in the potential confounders, including general characteristics, comorbidities, and lifestyle, indicating a similar effect on the pathology of liver damage caused by schistosome infection. There was no apparent difference in the incidence of common clinical symptoms. Furthermore, no significant difference was observed in the ultrasound findings, implying that the GAP and FTP groups shared a similar degree of liver lesion. With the exception of the abnormal rates of aspartate aminotransferase (AST), alkaline phosphatase (ALP), and hyaluronic acid (HA), the other serological indicators were comparable between the groups. Overall, the FTP is not a better option for controlling advanced schistosomiasis in China. It is important to reveal the precise mechanism underlying the pathogenesis of advanced schistosomiasis so that specific approaches to treating and preventing the development of advanced schistosomiasis can be developed and schistosomiasis can be eliminated in China.

  3. Disorders of bone and bone mineral metabolism.

    PubMed

    Komoroski, Monica; Azad, Nasrin; Camacho, Pauline

    2014-01-01

    Metabolic bone disorders are very common in the general population and untreated, they can cause a variety of neurologic symptoms. These diseases include osteoporosis, vitamin D deficiency, Paget's disease, and alterations in calcium, phosphorus, and magnesium metabolism. Diagnosis is made through analysis of metabolic bone blood chemistries as well as radiologic studies such as dual energy X-ray absorptiometry (DXA) scans, bone scans, and X-rays. Treatment options have advanced significantly in the past decade for osteoporosis and Paget's disease and mainly include antiresorptive therapy. New recommendations for treatment of primary hyperparathyroidism are discussed as well as therapy for calcium, phosphorus, and mineral disorders. © 2014 Elsevier B.V. All rights reserved.

  4. Advances in Surgical Reconstructive Techniques in the Management of Penile, Urethral, and Scrotal Cancer.

    PubMed

    Bickell, Michael; Beilan, Jonathan; Wallen, Jared; Wiegand, Lucas; Carrion, Rafael

    2016-11-01

    This article reviews the most up-to-date surgical treatment options for the reconstructive management of patients with penile, urethral, and scrotal cancer. Each organ system is examined individually. Techniques and discussion for penile cancer reconstruction include Mohs surgery, glans resurfacing, partial and total glansectomy, and phalloplasty. Included in the penile cancer reconstruction section is the use of penile prosthesis in phalloplasty patients after penectomy, tissue engineering in phallic regeneration, and penile transplantation. Reconstruction following treatment of primary urethral carcinoma and current techniques for scrotal cancer reconstruction using split-thickness skin grafts and flaps are described. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Introduction: multiple myeloma.

    PubMed

    Cook, Richard

    2008-09-01

    Multiple myeloma (MM) is the most common type of primary bone tumor, affecting approximately 50,000 patients in the United States. Although it is currently not curable, recent advancements in treatment are bringing myeloma closer to becoming a chronic disease instead of a terminal illness. To better understand the prevalence of MM as well as provide an overview of the costs associated with treatment. The goals of treatment in MM include eradicating all evidence of disease, controlling disease to prevent damage to target organs, preserving normal function and quality of life, relieving pain, and managing myeloma that is in remission. To achieve these goals, treatment must be individually tailored for each patient based on the patient's age, overall health status, symptoms, and laboratory test results. Advancements in the understanding of the pathogenesis of myeloma and the role of genetic mutations are leading to a new standard of treatment. Advancements in diagnostic technology, such as cytogenetic testing, are also being used to tailor treatment for each individual to work toward achieving better response rates, longer periods of remission, and improved quality of life. Increased costs associated with the improved therapies being used to treat MM, and the comorbid conditions associated with the disease, present a challenge to managed care. Health plans and formulary decision makers need to better understand the complexity of therapy to best use resources. The economic burden to the patient must also be considered when developing treatment strategies. Better understanding of the pathophysiology of MM, including the role of cytogenetics, is leading to the development and use of novel agents and treatment options. Head-to-head studies comparing treatments must be performed to best balance the costs associated with treatment and the benefits of improved survival rates and maintaining quality of life.

  6. Apatinib for the treatment of gastric cancer.

    PubMed

    Geng, Ruixuan; Li, Jin

    2015-01-01

    Antiangiogenesis therapy plays an important role in cancer treatment. Apatinib mesylate, a small molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, has been recommended as third-line treatment for metastatic gastric cancer patients. The current review summarizes the publications and conference reports relating to apatinib from preclinical and clinical research in gastric cancer. Apatinib showed good safety, tolerance and treatment efficacy in Phase I/II studies. In a Phase III study, apatinib prolonged the median overall survival of patients with chemotherapy-refractory metastatic gastric cancer by 55 days and the median progression-free survival by 25 days compared with placebo. Apatinib is a new treatment option for advanced gastric cancer. Apatinib is expected to have a broader application when it has been evaluated worldwide. The key issues are to find biomarkers and overcome drug resistance.

  7. Local Arterial Therapies in the Management of Unresectable Hepatocellular Carcinoma.

    PubMed

    Mouli, Samdeep K; Goff, Laura W

    2017-10-27

    Most patients with hepatocellular carcinoma present with intermediate to advanced disease, where curative therapies are no longer an option. These patients with intermediate to advanced disease represent a heterogeneous population with regard to tumor burden, liver function, and performance status. While the Barcelona Clinic Liver Cancer (BCLC) staging system offers guidelines for the management of these patients, strict adherence to these guidelines may limit treatment options for these patients. Several locoregional therapies exist for these patients, including conventional transarterial chemoembolization (cTACE), transarterial embolization (TAE), drug-eluting embolization (DEE), and radioembolization. Evidence is also emerging for the role of radiation therapy including most notably stereotactic body radiation therapy and proton therapy, although at the current time, clinical trial participation is encouraged. While cTACE is traditionally recommended for BCLC B disease, both cTACE and radioembolization are increasingly used for patients with intermediate disease, as well as in select patients with BCLC A and C disease. TAE and DEE are limited in their use currently, due to lack of clear survival benefits or clinical advantages over cTACE. While several studies have demonstrated similar OS between cTACE and radioembolization, radioembolization provides a longer time to progression and fewer toxicities compared to cTACE. This is particularly relevant in the setting of advanced BCLC B and early BCLC C disease, where patients may have limited reserve. Radioembolization also has additional roles as an alternative to ablation, inducing liver hypertrophy, treating patients with PVT, and downstaging lesions to transplant. Ongoing studies will further define the role of locoregional treatment potentially in combination with and in light of developments in systemic therapy.

  8. Therapeutic options for cutaneous lupus erythematosus: recent advances and future prospects

    PubMed Central

    Chang, Joshua; Werth, Victoria P.

    2017-01-01

    Introduction Treatment and prevention are of critical importance in patients with cutaneous lupus erythematosus (CLE), as the disease can have a devastating effect on patient well-being and quality of life. Areas Covered We conducted a selective search of the PubMed database for articles published between December 2010 and November 2015. This review encompasses both non-pharmaceutical (photoprotection, smoking cessation, drug withdrawal, and vitamin D replacement) and pharmaceutical (topicals, antimalarials, immunosuppressives, biologics, etc.) interventions used in the treatment of CLE. Expert Commentary Recent work has expanded our understanding of established therapies as well as introduced new treatments for consideration, though existing medications still prove inadequate for a subset of patients. Changes in trial design may help to alleviate this issue. PMID:27249209

  9. Use of cortical stimulation in neuropathic pain, tinnitus, depression, and movement disorders.

    PubMed

    Panov, Fedor; Kopell, Brian Harris

    2014-07-01

    Medical treatment must strike a balance between benefit and risk. As the field of neuromodulation develops, decreased invasiveness, in combination with maintenance of efficacy, has become a goal. We provide a review of the history of cortical stimulation from its origins to the current state. The first part discusses neuropathic pain and the nonpharmacological treatment options used. The second part covers transitions to tinnitus, believed by many to be another deafferentation disorder, its classification, and treatment. The third part focuses on major depression. The fourth section concludes with the discussion of the use of cortical stimulation in movement disorders. Each part discusses the development of the field, describes the current care protocols, and suggests future avenues for research needed to advance neuromodulation.

  10. Focal therapy as primary treatment for localized prostate cancer: definition, needs and future.

    PubMed

    Ouzzane, Adil; Betrouni, Nacim; Valerio, Massimo; Rastinehad, Ardeshir; Colin, Pierre; Ploussard, Guillaume

    2017-04-01

    Focal therapy (FT) may offer a promising treatment option in the field of low to intermediate risk localized prostate cancer. The aim of this concept is to combine minimal morbidity with cancer control as well as maintain the possibility of retreatment. Recent advances in MRI and targeted biopsy has improved the diagnostic pathway of prostate cancer and increased the interest in FT. However, before implementation of FT in routine clinical practice, several challenges are still to overcome including patient selection, treatment planning, post-therapy monitoring and definition of oncologic outcome surrogates. In this article, relevant questions regarding the key steps of FT are critically discussed and the main available energy modalities are analyzed taking into account their advantages and unmet needs.

  11. Treatment of phosphate retention: The earlier the better?

    PubMed Central

    Biggar, Patrick; Fung, Samuel K.S.; Ketteler, Markus

    2014-01-01

    Over the last 15 years, our knowledge and understanding of the underlying mechanisms involved in the regulation of calcium and phosphate homeostasis in chronic kidney disease have advanced dramatically. Contrary to general opinion in the 20th century that moderate hypercalcemia and hyperphosphatemia were acceptable in treating secondary hyperparathyroidism, the calcium and phosphate load is increasingly perceived to be a major trigger of vascular and soft tissue calcification. The current treatment options are discussed in view of historical developments and the expectations of the foreseeable future, focusing on the early treatment of hyperphosphatemia. At present, we lack indisputable evidence that active intervention using currently available drugs is of benefit to patients in chronic kidney disease stages 3 and 4. PMID:26877944

  12. The diagnosis and treatment of brain metastases in EGFR mutant lung cancer.

    PubMed

    Minchom, Anna; Yu, Ken C; Bhosle, Jaishree; O'Brien, Mary

    2014-05-01

    The epidemiology of non-small-cell lung cancer (NSCLC) has changed with a new pattern of disease emerging - a form of adenocarcinoma in mostly younger female patients, who are never or light smokers and more frequently in East Asian populations. Description of EGF receptor (EGFR) mutations has allowed new management strategies to evolve. Oral targeted therapies have broadened the treatment options in the advanced setting with the potential for periods of long term response. The brain is a common site of metastases with EGFR mutated lung cancer typically displaying asymptomatic, small volume, multiple lesions that respond to treatment. We explore the role of local and system therapies for brain metastases in this disease including the role of EGFR inhibitors.

  13. Depression and Anxiety in Parkinson's Disease.

    PubMed

    Schrag, Anette; Taddei, Raquel N

    2017-01-01

    Depression and anxiety are some of the most common comorbidities arising in patients with Parkinson's disease. However, their timely recognition and diagnosis are often hindered by overlap with other somatic features and a low rate of self-report. There is a need for greater awareness and for better assessment and treatment options are highly required. Currently available scales can serve as tools to monitor change over time and the effect of interventional strategies. Development of new therapeutic strategies, including nonpharmacological approaches such as transcranial magnetic stimulation and deep brain stimulation, may provide alternatives to currently available treatment approaches. In this chapter we will give an overview of the most recent advances in the diagnosis and treatment of these important nonmotor symptoms. © 2017 Elsevier Inc. All rights reserved.

  14. Tracking the behavior of different size fractions of dissolved organic matter in a full-scale advanced drinking water treatment plant.

    PubMed

    Quang, Viet Ly; Choi, Ilhwan; Hur, Jin

    2015-11-01

    In this study, five different dissolved organic matter (DOM) fractions, defined based on a size exclusion chromatography with simultaneous detection of organic carbon (OCD) and ultraviolet (UVD), were quantitatively tracked with a treatment train of coagulation/flocculation-sand filtration-ozonation-granular activated carbon (GAC) filtration in a full-scale advanced drinking water treatment plant (DWTP). Five DOM samples including raw water were taken after each treatment process in the DWTP every month over the period of three years. A higher abundance of biopolymer (BP) fraction was found in the raw water during spring and winter than in the other seasons, suggesting an influence of algal bloom and/or meltwater on DOM composition. The greater extent of removal was observed upon the coagulation/flocculation for high-molecular-weight fractions including BP and humic substances (HS) and aromatic moieties, while lower sized fractions were preferentially removed by the GAC filtration. Ozone treatment produced the fraction of low-molecular-weight neutrals probably resulting from the breakdown of double-bonded carbon structures by ozone oxidation. Coagulation/flocculation was the only process that revealed significant effects of influent DOM composition on the treatment efficiency, as revealed by a high correlation between the DOM removal rate and the relative abundance of HS for the raw water. Our study demonstrated that SEC-OCD-UVD was successful in monitoring size-based DOM composition for the advanced DWTP, providing an insight into optimizing the treatment options and the operational conditions for the removal of particular fractions within the bulk DOM.

  15. Constraining Second Language Word Order Optionality: Scrambling in Advanced English?German and Japanese?German Interlanguage

    ERIC Educational Resources Information Center

    Hopp, Holger

    2005-01-01

    This study documents knowledge of UG-mediated aspects of optionality in word order in the second language (L2) German of advanced English and Japanese speakers (n = 39). A bimodal grammaticality judgement task, which controlled for context and intonation, was administered to probe judgements on a set of scrambling, topicalization and remnant…

  16. Transantral distraction devices in correction of severe maxillary deformity in cleft patients.

    PubMed

    Shokirov, Shokhruh; Wangerin, Konrad

    2011-01-01

    Maxillary advancement by Le Fort I osteotomy in cleft patients has an average relapse of about 40-60 percent. With extraoral distraction devices it is possible to obtain an almost unlimited advancement of the upper jaw. Due to the social problems the retention period is normally reduced to some monthes. A relapse of 10-25 % can be seen in these cases. Le Fort I internal distraction osteogenesis offers an alternative to one-step orthognathic advancement, with advantages of gradual lengthening through scar and earlier treatment in growing patients. The objective of this study was to present our experience in the treatment of maxillary deficiency in cleft patients using transantral internal distraction devices. The distraction procedure was successfully accomplished in seventeen patients. For all the seventeen patients maxillary distraction device designed by Konrad Wangerin was used. The distraction distances were 8 to 24 mm. Preoperative, postoperative, and follow-up (12 and 24 months) lateral cephalogram measurements were compared including angular and linear changes. A good new bone was found that was formed in distraction pitch between lines of osteotomy. After distraction of median facial zone, occlusion and profile of soft tissues were considerably improved. All patients after postoperative time required final orthodontic treatment and their final occlusal relationships were satisfactory. The transantral distraction device is a new option for the treatment of severe maxillary hypoplasia in cleft patients.

  17. Recent advances in managing tricuspid regurgitation

    PubMed Central

    Del Forno, Benedetto; Lapenna, Elisabetta; Dalrymple-Hay, Malcom; Taramasso, Maurizio; Castiglioni, Alessandro; Alfieri, Ottavio; De Bonis, Michele

    2018-01-01

    Isolated tricuspid valve surgery is usually carried out with very high morbidity and mortality given the complexity of the affected patients. In light of this, trans-catheter tricuspid valve interventions have been emerging as an attractive alternative to surgery over the last few years. Although feasibility has been shown with a number of devices, clinical experience remains preliminary and associated with significant clinical and technical challenges. Here we describe currently available trans-catheter treatment options for severe tricuspid regurgitation implanted in different locations. PMID:29636903

  18. Inclusion body myositis – pathomechanism and lessons from genetics

    PubMed Central

    Murnyák, Balázs; Bodoki, Levente; Vincze, Melinda; Griger, Zoltán; Csonka, Tamás; Szepesi, Rita; Kurucz, Andrea; Dankó, Katalin

    2015-01-01

    Inclusion body myositis is a rare, late-onset myopathy. Both inflammatory and myodegenerative features play an important role in their pathogenesis. Overlapping clinicopathological entities are the familial inclusion body myopathies with or without dementia. These myopathies share several clinical and pathological features with the sporadic inflammatory disease. Therefore, better understanding of the genetic basis and pathomechanism of these rare familial cases may advance our knowledge and enable more effective treatment options in sporadic IBM, which is currently considered a relentlessly progressive incurable disease. PMID:28352694

  19. Chronic obstructive pulmonary disease: More than meets the eye

    PubMed Central

    Hatipoğlu, Umur

    2018-01-01

    Chronic obstructive pulmonary disease (COPD) is a major health problem which had not received the attention commensurate with the magnitude of its global burden. This is finally changing with the help of a vibrant community of health-care professionals, public officials, and academic researchers. Advances in characterization of the disease, treatment options, imaging modalities, and better understanding of the comorbidities promise to revolutionize how the disease is managed. COPD should no longer augur despair among physicians and patients. PMID:29387249

  20. Reconstruction of the premaxilla by segmental distraction osteogenesis for maxillary retrusion in cleft lip and palate.

    PubMed

    Kim, Bong Chul; Lee, Sang-Hwy; Park, Kyung-Ran; Jung, Young-Soo; Yi, Choong-Kook

    2014-03-01

    We present a strategy to target one of the main areas causing retruded maxilla, the premaxillary region for patients with cleft lip and palate (CLP). Advancement of the premaxilla by distraction osteogenesis is attempted, and the retruded anterior maxilla, the collapsed dental space, and the arch shape are sufficiently improved. This strategy also prevents deterioration of the velopharyngeal incompetency function. The procedure seems to be a good option for the treatment of maxillary retrusion and malocclusion for CLP.

  1. Cushing’s syndrome in childhood: update on genetics, treatment, and outcomes

    PubMed Central

    Lodish, Maya

    2015-01-01

    Purpose of review To provide an update on the genes associated with Cushing’s syndrome in children, as well as to familiarize the clinician with recent treatment guidelines and outcome data for children with Cushing’s syndrome. Recent findings The list of genes associated with Cushing’s syndrome continues to grow. In addition, treatment for childhood Cushing’s syndrome is evolving. As long-term follow-up data on children becomes available, clinicians need to be aware of the issues that require attention. Summary Knowledge of the specific genetic causes of Cushing’s syndrome has potential implications for treatment, surveillance, and counseling. Advances in surgical technique, radiation modalities, and medical therapies offer the potential for additional treatment options in Cushing’s syndrome. Early identification and management of post-treatment morbidities in children treated for Cushing’s syndrome is crucial in order to optimize care. PMID:25517021

  2. Age and treatment of kidney failure.

    PubMed

    Elliott, Meghan J; Tam-Tham, Helen; Hemmelgarn, Brenda R

    2013-05-01

    This review discusses issues related to treatment of chronic kidney disease, and kidney failure in particular, among older adults. A substantial proportion of older adults have chronic kidney disease and progress to kidney failure. There is considerable variability in treatment practices for advanced kidney disease among older adults, and evidence that treatment decisions such as dialysis initiation may be made without adequate preparation. When initiated, survival among older adults on chronic dialysis remains poor, and is associated with a significant decline in functional status. There is also evidence to suggest that dialysis initiation may not reflect overall treatment goals of elderly patients, but rather a lack of clear communication between patients and health practitioners, and underdeveloped conservative care programs in many centers. Kidney failure is common among older adults. When considering treatment options for kidney failure, patient priorities, preferences, and symptoms should be taken into account, using a shared decision-making approach.

  3. Integration of advanced oxidation processes at mild conditions in wet scrubbers for odourous sulphur compounds treatment.

    PubMed

    Vega, Esther; Martin, Maria J; Gonzalez-Olmos, Rafael

    2014-08-01

    The effectiveness of different advanced oxidation processes on the treatment of a multicomponent aqueous solution containing ethyl mercaptan, dimethyl sulphide and dimethyl disulphide (0.5 mg L(-1) of each sulphur compound) was investigated with the objective to assess which one is the most suitable treatment to be coupled in wet scrubbers used in odour treatment facilities. UV/H2O2, Fenton, photo-Fenton and ozone treatments were tested at mild conditions and the oxidation efficiency obtained was compared. The oxidation tests were carried out in magnetically stirred cylindrical quartz reactors using the same molar concentration of oxidants (hydrogen peroxide or ozone). The results show that ozone and photo-Fenton are the most efficient treatments, achieving up to 95% of sulphur compounds oxidation and a mineralisation degree around 70% in 10 min. Furthermore, the total costs of the treatments taking into account the capital and operational costs were also estimated for a comparative purpose. The economic analysis revealed that the Fenton treatment is the most economical option to be integrated in a wet scrubber to remove volatile organic sulphur compounds, as long as there are no space constraints to install the required reactor volume. In the case of reactor volume limitation or retrofitting complexities, the ozone and photo-Fenton treatments should be considered as viable alternatives. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Stem cell transplant in inflammatory bowel disease: a promising modality of treatment for a complicated disease course.

    PubMed

    Salem, George A; Selby, George B

    2017-01-01

    Inflammatory bowel disease (IBD) is a complex, relapsing and remitting, disease characterized by an exaggerated immune response in a susceptible host. The symptoms and complications of the disease can be debilitating. Advances in medical treatment in the last decade changed the course of the disease in many patients. Despite the use of novel agents for controlling disease, a proportion of patients' disease courses continue to be either refractory, or become resistant, to available therapeutic options. Stem-cell therapy, with hematopoietic stem cells (HSCs) or mesenchymal stem cells (MSCs), is a promising modality of treatment for severe refractory cases, mainly Crohn's disease (CD) patients. HSCs have the ability to migrate to damaged tissue, which provides them with further properties to differentiate to epithelial or immune-modulatory cells to restore normal mucosal tissue and integrity. MSCs therapy is a promising model for patients with perianal CD due to their immunosuppressive properties, ability to migrate to areas of injury, and demonstration of colonic healing, including fistulizing tracts. The results from ongoing clinical trials will provide a valuable understanding of the future of stem-cell therapy as a treatment option in refractory cases of IBD, a disease whose pathogenesis remains unknown, and is notoriously difficult to treat.

  5. [Portal hypertension. Evidence-based guide].

    PubMed

    Mercado, Miguel Angel; Orozco Zepeda, Héctor; Plata-Muñoz, Juan José

    2004-01-01

    Treatment of portal hypertension has evolved widely during the last decades. Advances in physiopathology have allowed better application of therapeutic options and also have permitted to know the natural history of varices and variceal bleeding, predicting which patients have a higher risk of bleeding. It also permits probability of designing patient treatment. According to liver function and subadjacent liver disease, it is possible to offer different alternatives within the three possible scenarios (primary prophylaxis, acute bleeding episode, and secondary prophylaxis). For primary prophylaxis, pharmacotherapy offers the best choice. Endoscopic banding is also growing in these scenarios and probably will be accepted in the near future. For the acute bleeding episode, endoscopic therapy (sclerosis and/or bands) and/or pharmacologic therapy (octreotide, terlipresin) represent best choice, considering TIPS as a rescue option. Surgery is not used routinely in this scenario in most centers. For secondary prophylaxis, pharmaco- and endoscopic therapy are first-line treatments, while TIPS and surgery as second-line treatments. TIPS is mainly used in patients on a waiting list for liver transplantation. Surgery offers good results for low-risk patients, with good liver function and with portal blood-flow preserving procedures (selective shunts, extensive devascularizations). Liver transplantation is recommended for patients with poor liver function because together with portal hypertension, it treats subadjacent liver disease.

  6. Revascularization procedures for Kienböck disease.

    PubMed

    Kakar, Sanjeev; Giuffre, Jennifer L; Shin, Alexander Y

    2011-03-01

    The goals of treatment in Kienböck disease include preservation of wrist function, maintaining normal wrist kinematics, and revascularization of the necrotic lunate when and if possible. A variety of pedicled vascularized bone graft options exist and include but are not limited to pedicled grafts from the volar radius, dorsal radius, metacarpal heads or bases, and pisiform. Of the various treatment options, pedicled vascularized bone grafts from the dorsal distal radius based on the fourth and fifth extensor compartment arteries has been successful in the revascularization of the necrotic lunate at our institution. Vascularized bone grafting is an attractive alternative to conventional bone grafting by improving the local biological environment and thereby promoting revascularization. Recent advances in the anatomy and physiology of vascularized pedicled bone grafts have increased our ability to apply them to the treatment of Kienböck disease. The purpose of this article is to describe the various types of pedicled vascularized bone graft available, to detail the vascular anatomy of the dorsal distal radius, and to describe the surgical technique of our preferred vascularized bone graft (the fourth+fifth extensor compartment artery graft). In addition, the indications, contraindications, and outcomes are described.

  7. Castration-resistant prostate cancer: targeted therapies.

    PubMed

    Leo, S; Accettura, C; Lorusso, V

    2011-01-01

    Castration-resistant prostate cancer (CRPC) refers to patients who no longer respond to surgical or medical castration. Standard treatment options are limited. To review the concepts and rationale behind targeted agents currently in late-stage clinical testing for patients with CRPC. Novel targeted therapies in clinical trials were identified from registries. The Medline database was searched for all relevant reports published from 1996 to October 2009. Bibliographies of the retrieved articles and major international meeting abstracts were hand-searched to identify additional studies. Advances in our understanding of the molecular mechanisms underlying prostate cancer (PCa) progression have translated into a variety of treatment approaches. Agents targeting androgen receptor activation and local steroidogenesis, angiogenesis, immunotherapy, apoptosis, chaperone proteins, the insulin-like growth factor (IGF) pathway, RANK ligand, endothelin receptors, and the Src family kinases are entering or have recently completed accrual to phase III trials for patients with CRPC. There has been an increase in the understanding of the mechanisms of progression of CRPC. A number of new agents targeting mechanisms of PCa progression with early promising results are in clinical trials and have the potential to provide novel treatment options for CRPC in the near future. Copyright © 2011 S. Karger AG, Basel.

  8. Surgical treatment of dystonia.

    PubMed

    Cury, Rubens Gisbert; Kalia, Suneil Kumar; Shah, Binit Bipin; Jimenez-Shahed, Joohi; Prashanth, Lingappa Kumar; Moro, Elena

    2018-05-28

    Treatment of dystonia should be individualized and tailored to the specific needs of patients. Surgical treatment is an important option in medically refractory cases. Several issues regarding type of the surgical intervention, targets, and predict factors of benefit are still under debate. Areas covered: To date, several clinical trials have proven the benefit and safety of deep brain stimulation (DBS) for inherited and idiopathic isolated dystonia, whereas there is still insufficient evidence in combined and acquired dystonia. The globus pallidus internus (GPi) is the target with the best evidence, but data on the subthalamic nucleus seems also to be promising. Evidence suggests that younger patients with shorter disease duration experience greater benefit following DBS. Pallidotomy and thalamotomy are currently used in subset of carefully selected patients. The development of MRI-guided focused ultrasound might bring new options to ablation approach in dystonia. Expert commentary: GPi-DBS is effective and safe in isolated dystonia and should not be delayed when symptoms compromise quality of life and functionality. Identifying the best candidates to surgery on acquired and combined dystonias is still necessary. New insights about pathophysiology of dystonia and new technological advances will undoubtedly help to tailor surgery and optimize clinical effects.

  9. Pediatric status epilepticus: improved management with new drug therapies?

    PubMed

    Verrotti, Alberto; Ambrosi, Michela; Pavone, Piero; Striano, Pasquale

    2017-06-01

    Status Epilepticus (SE) is the most common neurological emergency of childhood. It requires prompt administration of appropriately selected anti-seizure medications. Areas covered: Following a distinction between estabilished and emergent drugs, we present pharmacological treatment options and their clinical utility in children, with a short mention on alternatives to drug treatment. We also propose an algorithm for the management of pediatric SE. For this review a Pubmed, Medline and Embase search was performed. Expert opinion: In early SE in children, in the prehospital setting, rectal diazepam or buccal midazolam are efficacious drugs; whereas in the hospital setting, intravenous lorazepam or diazepam are indicated. As regard estabilished stage of SE, in addition to the 'classic' compounds, such as phenytoin and phenobarbital, other drugs such as valproic acid, levetiracetam and lacosamide have been demonstrated efficacious. Treatment recommendations of refractory SE depend on retrospective case series and uncontrolled studies. We reported experiences about the use of midazolam, propofol, ketamine and lidocaine. They could be a valid option, but further prospective studies are necessary. Over the last few decades, important advances in basic mechanisms underlying refractory SE have been achieved, but few data are available regarding management of these stages.

  10. Advances in pediatric asthma and atopic dermatitis.

    PubMed

    Foroughi, Shabnam; Thyagarajan, Ananth; Stone, Kelly D

    2005-10-01

    Allergic diseases, including asthma, allergic rhinitis, atopic dermatitis, food allergy, and urticaria are common in general pediatric practice. This review highlights several significant advances in pediatric allergy over the past year, focusing on asthma and atopic dermatitis. With increasing options for the treatment of allergic diseases, much work is now focused on methods for individualizing treatments to a patient's phenotype and genotype. Progress over the past year includes the characterization of effects of regular albuterol use in patients with genetic variations in the beta-adrenergic receptor. Maintenance asthma regimens for children in the first years of life are also an ongoing focus. The relation between upper airway allergic inflammation and asthma has continued to accumulate support and now extends to the middle ear. Environmental influences on asthma and interventions have been described, including environmental controls for asthma and the role of air pollution on lung development in children. Finally, concerns have been raised regarding the use of topical immunomodulators in young children with atopic dermatitis. Progress continues in the care of children with atopic diseases. Attention to treatment with appropriate medications, patient-individualized environmental controls, and extensive education are the keys to successfully treating atopic children. This review highlights several recent advances but is not intended to be a comprehensive review.

  11. The resistance mechanisms and treatment strategies for EGFR-mutant advanced non-small-cell lung cancer

    PubMed Central

    Zhong, Wen-Zhao; Zhou, Qing; Wu, Yi-Long

    2017-01-01

    Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have been established as the standard therapy for EGFR-sensitizing mutant advanced non-small-cell lung cancer (NSCLC). However, patients ultimately develop resistance to these drugs. There are several mechanisms of both primary and secondary resistance to EGFR-TKIs. The primary resistance mechanisms include point mutations in exon 18, deletions or insertions in exon 19, insertions, duplications and point mutations in exon 20 and point mutation in exon 21 of EGFR gene. Secondary resistance to EGFR-TKIs is due to emergence of T790M mutation, activation of alternative signaling pathways, bypassing downstream signaling pathways and histological transformation. Strategies to overcome these intrinsic and acquired resistance mechanisms are complex. With the development of the precision medicine for advanced NSCLC, available systemic and local treatment options have expanded, requiring new clinical algorithms that take into account resistance mechanism. Though combination therapy is emerging as the standard of to overcome resistance mechanisms. Personalized treatment modalities based on molecular diagnosis and monitoring is essential for disease management. Emerging data from the ongoing clinical trials on combination therapy of third generation TKIs and antibodies in EGFR mutant NSCLC are promising for better survival outcomes. PMID:29050366

  12. Malignant Bowel Obstruction in Advanced Gynecologic Cancers: An Updated Review from a Multidisciplinary Perspective

    PubMed Central

    Lee, Yeh Chen; Jivraj, Nazlin; O'Brien, Catherine; Chawla, Tanya; Shlomovitz, Eran; Buchanan, Sarah; Lau, Jenny; Croke, Jennifer; Allard, Johane P.; Dhar, Preeti; Laframboise, Stephane; Ferguson, Sarah E.; Dhani, Neesha; Butler, Marcus; Ng, Pamela; Stuart-McEwan, Terri; Savage, Pamela; Tinker, Lisa; Oza, Amit M.

    2018-01-01

    Malignant bowel obstruction (MBO) is a major complication in women with advanced gynecologic cancers which imposes a significant burden on patients, caregivers, and healthcare systems. Symptoms of MBO are challenging to palliate and result in progressive decompensation of already vulnerable patients with limited therapeutic options and a short prognosis. However, there is a paucity of guidelines or innovative approaches to improve the care of women who develop MBO. MBO is a complex clinical situation that requires a multidisciplinary approach to ensure the appropriate treatment modality and interprofessional care to optimally manage these patients. This review summarizes the current literature on the different approaches targeting MBO management including surgical intervention, chemotherapy, total parenteral nutrition, and pharmacological treatment. In addition, the impact of MBO management on patients' quality of life (QOL) is examined. This article focuses on the challenges in developing evidence-based treatment guidelines for MBO and barriers in clinical trial design for MBO and proposes strategies to advance the MBO management. Collaboration is essential to design studies that may improve the overall care and quality of life for these patients. Prospective data are needed to inform clinical practice, establish a new benchmark for evidence-based MBO management, and better understand the biology of MBO. PMID:29887891

  13. Diode laser treatment and clinical management of multiple oral lesions in patients with hereditary haemorrhagic telangiectasia.

    PubMed

    Favia, G; Tempesta, A; Limongelli, L; Suppressa, P; Sabbà, C; Maiorano, E

    2016-05-01

    Hereditary haemorrhagic telangiectasia (HHT) is rare, and characterised by vascular dysplasia that leads to various symptoms including visceral arteriovenous malformations and mucocutaneous telangiectatic lesions. Our aim was to describe the clinical features and options for the treatment of multiple oral lesions, and to illustrate the efficacy of the diode laser in the treatment of early (<2mm) and advanced lesions (2mm or more). We report 24 patients with 1200 oral telangiectatic lesions, which were often associated with regular bleeding (from monthly to daily), superinfection, pain, and swelling, and treated with multiple sessions of laser according to the number and size of the lesions. Early lesions were treated with a single laser impulse in ultrapulsed mode, and advanced lesions with repeated laser impulses in pulsed mode (t-on 200ms/t-off 500ms), at a power of 8W. Early lesions healed completely after laser photocoagulation with no operative or postoperative complications, while advanced lesions improved with a remarkable reduction in size but more discomfort. Protective occlusal plates were sometimes used to reduce the incidence of new lesions caused by dental trauma. The treatment of oral telangiectatic lesions is still being debated, and it is important to improve quality of life for patients. Diode laser surgery could be an effective treatment for oral lesions in those with hereditary haemorrhagic telangiectasia. Copyright © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  14. Serous Carcinoma of the Uterine Cervix, an Extremely Rare Aggressive Entity: A Literature Review.

    PubMed

    Jonska-Gmyrek, Joanna; Zolciak-Siwinska, Agnieszka; Gmyrek, Leszek; Michalski, Wojciech; Poniatowska, Grazyna; Fuksiewicz, Malgorzata; Wiechno, Pawel; Kucharz, Jakub; Kowalska, Maria; Kotowicz, Beata

    2018-01-01

    Serous carcinoma of the uterine cervix (USCC) is an extremely rare subtype. To establish the treatment strategy in patients with USCC is an important issue. MEDLINE (PubMed) was searched for all articles published after the first publication by Lurie et al. [Eur J Obstet Gynecol Reprod Biol 1991; 40: 79-81], reporting woman diagnosed with USCC. Because of limited numbers of studies on the topic of the study, we could not keep a restriction of eliminating smaller sample sizes. A search of PubMed demonstrated that 113 cases of USCC have been reported in the literature since the first publication. The current treatment modality adopted for early cervical cancer is hysterectomy with bilateral iliac-obturator lymphadenectomy and postoperative radiotherapy (RT) or radiochemotherapy (RT-CT) if risk factors for cervical carcinoma appear. The treatment strategy for locally advanced USCC is preoperative RT-CT or chemotherapy (CHTH) with the intention to treat the patient surgically. The treatment option for disseminated disease is CHTH with paclitaxel and carboplatin. Risk factors and a more advanced clinical stage of USCC have an impact on poor outcomes despite the use of standard treatment methods, adapted for cervical cancer. The outside-pelvic failures tend to seek effective systemic treatment. © 2018 S. Karger AG, Basel.

  15. Nitrosamines in pilot-scale and full-scale wastewater treatment plants with ozonation.

    PubMed

    Gerrity, Daniel; Pisarenko, Aleksey N; Marti, Erica; Trenholm, Rebecca A; Gerringer, Fred; Reungoat, Julien; Dickenson, Eric

    2015-04-01

    Ozone-based treatment trains offer a sustainable option for potable reuse applications, but nitrosamine formation during ozonation poses a challenge for municipalities seeking to avoid reverse osmosis and high-dose ultraviolet (UV) irradiation. Six nitrosamines were monitored in full-scale and pilot-scale wastewater treatment trains. The primary focus was on eight treatment trains employing ozonation of secondary or tertiary wastewater effluents, but two treatment trains with chlorination or UV disinfection of tertiary wastewater effluent and another with full advanced treatment (i.e., reverse osmosis and advanced oxidation) were also included for comparison. N-nitrosodimethylamine (NDMA) and N-nitrosomorpholine (NMOR) were the most prevalent nitrosamines in untreated (up to 89 ng/L and 67 ng/L, respectively) and treated wastewater. N-nitrosomethylethylamine (NMEA) and N-nitrosodiethylamine (NDEA) were detected at one facility each, while N-nitrosodipropylamine (NDPrA) and N-nitrosodibutylamine (NDBA) were less than their method reporting limits (MRLs) in all samples. Ozone-induced NDMA formation ranging from <10 to 143 ng/L was observed at all but one site, but the reasons for the variation in formation remain unclear. Activated sludge, biological activated carbon (BAC), and UV photolysis were effective for NDMA mitigation. NMOR was also removed with activated sludge but did not form during ozonation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Efficacy, safety and predictive indicators of apatinib after multilines treatment in advanced nonsquamous nonsmall cell lung cancer: Apatinib treatment in nonsquamous NSCLC.

    PubMed

    Wu, Di; Liang, Li; Nie, Ligong; Nie, Jun; Dai, Ling; Hu, Weiheng; Zhang, Jie; Chen, Xiaoling; Han, Jindi; Ma, Xiangjuan; Tian, Guangming; Han, Sen; Long, Jieran; Wang, Yang; Zhang, Ziran; Xin, Tao; Fang, Jian

    2018-03-24

    Patients with advanced nonsquamous nonsmall cell lung cancer (NSCLC) who experienced progression with two or more lines chemotherapy have no treatment options that clearly confer a survival benefit. As a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, apatinib has a certain antitumor effect for various solid tumors. The present study evaluated the efficacy and safety of apatinib in advanced nonsquamous NSCLC as salvage treatment in Chinese real-world practice. Twenty-eight patients were enrolled in this observational study from October 2015 to May 2017. Progression-free survival (PFS) and overall survival (OS) were graphed by Kaplan-Meier curve and intergroup comparisons were carried out by log-rank test. Objective response rate (ORR), disease control rate (DCR) and adverse effects (AEs) were also evaluated. Seven patients obtained partial response, and 18 obtained stable disease, representing an ORR of 26% and a DCR of 93%. Median PFS and OS were 3 (95% confidence interval [CI] 2.6-3.4) and 7.4 (95% CI 1.3-13.5) months, respectively. The efficacy analysis showed that Eastern Cooperative Oncology Group (ECOG) performance status 0-1 was correlated with prolonged OS and PFS (P < 0.05), and hypertension during apatinib treatment was correlated with prolonged OS (P < 0.05). Cox regression showed that ECOG performance status (P < 0.01) (RR = 0.231) (95% CI 0.083-0.642) and hypertension during apatinib treatment (P = 0.05) were predictive indicators for apatinib treatment. Grade 3-4 AEs with incidences of 10% or greater were hypertension (21%), hand-foot syndrome (14%) and proteinuria (11%) which could be relieved by dose reduction. In conclusion, apatinib has a certain therapeutic effect in patients with advanced nonsquamous NSCLC. ECOG performance status and hypertension during apatinib might be predictive indicators for treatment efficacy. © 2018 John Wiley & Sons Australia, Ltd.

  17. Advance care planning in CKD/ESRD: an evolving process.

    PubMed

    Holley, Jean L

    2012-06-01

    Advance care planning was historically considered to be simply the completion of a proxy (health care surrogate designation) or instruction (living will) directive that resulted from a conversation between a patient and his or her physician. We now know that advance care planning is a much more comprehensive and dynamic patient-centered process used by patients and families to strengthen relationships, achieve control over medical care, prepare for death, and clarify goals of care. Some advance directives, notably designated health care proxy documents, remain appropriate expressions of advance care planning. Moreover, although physician orders, such as do-not-resuscitate orders and Physician Orders for Life-Sustaining Treatment, may not be strictly defined as advance directives, their completion, when appropriate, is an integral component of advance care planning. The changing health circumstances and illness trajectory characteristic of ESRD mandate that advance care planning discussions adapt to a patient's situation and therefore must be readdressed at appropriate times and intervals. The options of withholding and withdrawing dialysis add ESRD-specific issues to advance care planning in this population and are events each nephrologist will at some time confront. Advance care planning is important throughout the spectrum of ESRD and is a part of nephrology practice that can be rewarding to nephrologists and beneficial to patients and their families.

  18. Definitive, Preoperative, and Palliative Radiation Therapy of Esophageal Cancer.

    PubMed

    Fokas, Emmanouil; Rödel, Claus

    2015-10-01

    Long-term survival in patients with esophageal cancer remains dismal despite the recent improvements in surgery, the advances in radiotherapy (RT) technology, and the refinement of systemic treatments, including the advent of targeted therapies. Although surgery constitutes the treatment of choice for early-stage disease (stage I), a multimodal approach, including preoperative or definitive chemoradiotherapy (CRT) and perioperative chemotherapy, is commonly pursued in patients with locally advanced disease. A review of the literature was performed to assess the role of RT, alone or in combination with chemotherapy, in the management of esophageal cancer. Evidence from large, randomized phase III trials and meta-analyses supports the application of perioperative chemotherapy alone or preoperative concurrent CRT in patients with lower esophageal and esophagogastric junction adenocarcinomas. Preoperative CRT but not preoperative chemotherapy alone is now routinely used in patients with locally advanced squamous cell carcinoma (SCC). Additionally, definitive CRT without surgery has also emerged as a valuable approach in the management of resectable esophageal SCC to avoid surgery-related morbidity and mortality, whereas salvage surgery is reserved for those with persistent disease. Furthermore, brachytherapy offers a valuable option in the palliative treatment of patients with locally advanced, unresponsive disease. Fluorodeoxyglucose-positron emission tomography (FDG-PET) can facilitate a more accurate treatment response assessment and patient selection. Finally, the development of modern RT techniques, such as intensity-modulated and image-guided RT as well as FDG-PET-based RT planning, could further increase the therapeutic ratio of CRT. Altogether, CRT constitutes an important tool in the treatment armamentarium for esophageal cancer. Further optimization of CRT using modern technology and imaging, targeted therapies, and newer chemotherapeutic agents is a major challenge and should be the goal of future research and clinical trials.

  19. Current Advances in Detection and Treatment of Babesiosis

    PubMed Central

    Mosqueda, J; Olvera-Ramírez, A; Aguilar-Tipacamú, G; Cantó, GJ

    2012-01-01

    Babesiosis is a disease with a world-wide distribution affecting many species of mammals principally cattle and man. The major impact occurs in the cattle industry where bovine babesiosis has had a huge economic effect due to loss of meat and beef production of infected animals and death. Nowadays to those costs there must be added the high cost of tick control, disease detection, prevention and treatment. In almost a century and a quarter since the first report of the disease, the truth is: there is no a safe and efficient vaccine available, there are limited chemotherapeutic choices and few low-cost, reliable and fast detection methods. Detection and treatment of babesiosis are important tools to control babesiosis. Microscopy detection methods are still the cheapest and fastest methods used to identify Babesia parasites although their sensitivity and specificity are limited. Newer immunological methods are being developed and they offer faster, more sensitive and more specific options to conventional methods, although the direct immunological diagnoses of parasite antigens in host tissues are still missing. Detection methods based on nucleic acid identification and their amplification are the most sensitive and reliable techniques available today; importantly, most of those methodologies were developed before the genomics and bioinformatics era, which leaves ample room for optimization. For years, babesiosis treatment has been based on the use of very few drugs like imidocarb or diminazene aceturate. Recently, several pharmacological compounds were developed and evaluated, offering new options to control the disease. With the complete sequence of the Babesia bovis genome and the B. bigemina genome project in progress, the post-genomic era brings a new light on the development of diagnosis methods and new chemotherapy targets. In this review, we will present the current advances in detection and treatment of babesiosis in cattle and other animals, with additional reference to several apicomplexan parasites. PMID:22360483

  20. Looking for fungi in all the right places: screening for cryptococcal disease and other AIDS-related mycoses among patients with advanced HIV disease.

    PubMed

    Greene, Greg; Sriruttan, Charlotte; Le, Thuy; Chiller, Tom; Govender, Nelesh P

    2017-03-01

    As HIV treatment programmes scale up to meet the UNAIDS 90-90-90 goals, care must be taken to start antiretroviral treatment safely in patients with advanced disease (CD4 counts <200 cells/μl) who are simultaneously at risk for opportunistic infections and immune reconstitution inflammatory syndrome. Invasive fungal diseases pose a great threat at this critical time point, though the development of inexpensive and highly accurate rapid diagnostic tests has changed the approach HIV programmes are taking to reduce the high mortality associated with these opportunistic infections. This article summarizes recent advances and findings in fungal opportunistic infection diagnostics with a focus on screening to prevent cryptococcal meningitis. Cryptococcal antigen (CrAg) screening using a lateral flow assay platform is cost-effective and feasible to implement as either a laboratory reflex or point-of-care test. Recent CrAg screening pilots have elucidated the varying prevalence of cryptococcal antigenemia across geographic regions, which may aid programme planning. Evidence from recently completed clinical trials provides a strong motivation for the use of CrAg titer to refine treatment options for patients with subclinical cryptococcal disease. Although several operational barriers to programme effectiveness still need to be addressed, the utility of CrAg screening using inexpensive and accurate antigen assays has been demonstrated in real-world HIV programmes, paving the way for development and testing of other fungal opportunistic infection screening strategies and for an integrated advanced HIV disease testing package to reduce AIDS mortality and ensure safe antiretroviral treatment initiation.

  1. Systems Analysis of Life Support for Long-Duration Missions

    NASA Technical Reports Server (NTRS)

    Drysdale, Alan E.; Maxwell, Sabrina; Ewert, Michael K.; Hanford, Anthony J.

    2000-01-01

    Work defining advanced life support (ALS) technologies and evaluating their applicability to various long-duration missions has continued. Time-dependent and time-invariant costs have been estimated for a variety of life support technology options, including International Space Station (ISS) environmental control and life support systems (ECLSS) technologies and improved options under development by the ALS Project. These advanced options include physicochemical (PC) and bioregenerative (BIO) technologies, and may in the future include in-situ resource utilization (ISRU) in an attempt to reduce both logistics costs and dependence on supply from Earth. PC and bioregenerative technologies both provide possibilities for reducing mission equivalent system mass (ESM). PC technologies are most advantageous for missions of up to several years in length, while bioregenerative options are most appropriate for longer missions. ISRU can be synergistic with both PC and bioregenerative options.

  2. Gamma knife radiosurgery for essential tremor: A Case report and review of the literature

    PubMed Central

    2010-01-01

    Approximately 5 million people in America are affected by essential tremors (ET), which are classified as a type of benign movement disorder. This disease manifests as tremors that usually occur in the hands, but they may also be present in the head, face, tongue, and lower limbs. Radiofrequency thalamotomy (RF) and deep brain stimulation (DBS) are common invasive procedures with proven track records that are used to treat ET. Although these procedures have high success rates, they still put patients at risk of potential side effects and are invasive by nature. Thalamotomy using the gamma knife (GK) also produces favorable outcomes in treating tremors, without the complications associated with invasive neurosurgery procedures. This report describes the presenting symptoms and extended treatment outcome for a patient with an advanced case of ET, who received GK thalamotomy treatment six years ago. Because of this non-invasive treatment, she regained the ability to paint and live with an improved quality of life. We also discuss and review the relevant literature regarding the risks and benefits of this treatment modality. GK thalamotomy is one effective option for the treatment of ET, and due to its noninvasive nature, it has a different risk profile than neurosurgery. We suggest that GK thalamotomy should be presented as one viable treatment option to all ET patients, and should be recommended to those who would be best served by less invasive treatment techniques. PMID:20307307

  3. Bazedoxifene exhibits antiestrogenic activity in animal models of tamoxifen-resistant breast cancer: implications for treatment of advanced disease.

    PubMed

    Wardell, Suzanne E; Nelson, Erik R; Chao, Christina A; McDonnell, Donald P

    2013-05-01

    There is compelling evidence to suggest that drugs that function as pure estrogen receptor (ER-α) antagonists, or that downregulate the expression of ER-α, would have clinical use in the treatment of advanced tamoxifen- and aromatase-resistant breast cancer. Although such compounds are currently in development, we reasoned, based on our understanding of ER-α pharmacology, that there may already exist among the most recently developed selective estrogen receptor modulators (SERM) compounds that would have usage as breast cancer therapeutics. Thus, our objective was to identify among available SERMs those with unique pharmacologic activities and to evaluate their potential clinical use with predictive models of advanced breast cancer. A validated molecular profiling technology was used to classify clinically relevant SERMs based on their impact on ER-α conformation. The functional consequences of these observed mechanistic differences on (i) gene expression, (ii) receptor stability, and (iii) activity in cellular and animal models of advanced endocrine-resistant breast cancer were assessed. The high-affinity SERM bazedoxifene was shown to function as a pure ER-α antagonist in cellular models of breast cancer and effectively inhibited the growth of both tamoxifen-sensitive and -resistant breast tumor xenografts. Interestingly, bazedoxifene induced a unique conformational change in ER-α that resulted in its proteasomal degradation, although the latter activity was dispensable for its antagonist efficacy. Bazedoxifene was recently approved for use in the European Union for the treatment of osteoporosis and thus may represent a near-term therapeutic option for patients with advanced breast cancer. ©2013 AACR.

  4. Increasing use of radical prostatectomy for locally advanced prostate cancer in the USA and Germany: a comparative population-based study.

    PubMed

    Hager, B; Kraywinkel, K; Keck, B; Katalinic, A; Meyer, M; Zeissig, S R; Scheufele, R; Wirth, M P; Huber, J

    2017-03-01

    Current guidelines do not recommend a preferred treatment modality for locally advanced prostate cancer. The aim of the study was to compare treatment patterns found in the USA and Germany and to analyze possible trends over time. We compared 'Surveillance Epidemiology and End Results' (SEER) data (USA) with reports from four German federal epidemiological cancer registries (Eastern Germany, Bavaria, Rhineland-Palatinate, Schleswig-Holstein), both from 2004 to 2012. We defined locally advanced prostate cancer as clinical stage T3 or T4. Exclusion criteria were metastatic disease and age over 79 years. We identified 9127 (USA) and 11 051 (Germany) patients with locally advanced prostate cancer. The share was 2.1% in the USA compared with 6.0% in Germany (P<0.001). In the United States, the utilization of radiotherapy (RT) and radical prostatectomy (RP) was comparably high with 42.0% (RT) and 42.8% (RP). In Germany, the major treatment option was RP with 36.7% followed by RT with 22.1%. During the study period, the use of RP increased in both countries (USA P=0.001 and Germany P=0.003), whereas RT numbers declined (USA P=0.003 and Germany P=0.002). The share of adjuvant RT (aRT) was similar in both countries (USA 21.7% vs Germany 20.7%). We found distinctive differences in treating locally advanced prostate cancer between USA and Germany, but similar trends over time. In the last decade, a growing number of patients underwent RP as a possible first step within a multimodal concept.

  5. Advances in immunotherapy for the treatment of glioblastoma.

    PubMed

    Tivnan, Amanda; Heilinger, Tatjana; Lavelle, Ed C; Prehn, Jochen H M

    2017-01-01

    Glioblastoma (GBM) is an aggressive brain tumour, associated with extremely poor prognosis and although there have been therapeutic advances, treatment options remain limited. This review focuses on the use of immunotherapy, harnessing the power of the host's immune system to reject cancer cells. Key challenges in glioma specific immunotherapy as with many other cancers are the limited immunogenicity of the cancer cells and the immunosuppressive environment of the tumour. Although specific antigens have been identified in several cancers; brain tumours, such as GBM, are considered poorly immunogenic. However, as detailed in this review, strategies aimed at circumventing these challenges are showing promise for GBM treatment; including identification of glioma specific antigens and endogenous immune cell activation in an attempt to overcome the immunosuppressive environment which is associated with GBM tumours. An up-to-date summary of current Phase I/II and ongoing Phase III GBM immunotherapy clinical trials is provided in addition to insights into promising preclinical approaches which are focused predominantly on increased induction of Type 1 helper T cell (T h 1) immune responses within patients.

  6. Emerging Role of Immunotherapy in Advanced Urothelial Carcinoma.

    PubMed

    Koshkin, Vadim S; Grivas, Petros

    2018-04-11

    Advanced urothelial carcinoma (aUC) has long been treated preferably with cisplatin-based chemotherapy, but many patients are cisplatin-ineligible whereas for those who progress on a platinum-based regimen treatment options are limited. We review key recent data regarding immune checkpoint inhibitors that are changing this treatment landscape. Since May 2016, five different agents targeting the PD-1/PD-L1 pathway (atezolizumab, pembrolizumab, nivolumab, avelumab, durvalumab) have received FDA approval for the treatment of aUC in the platinum-refractory setting, while pembrolizumab and atezolizumab are FDA-approved for cisplatin-ineligible patients in the first-line setting. Clinical outcomes and safety profiles of these agents appear relatively comparable across separate trials; however, only pembrolizumab is supported by level I evidence from a large randomized phase III trial showing overall survival benefit over conventional cytotoxic salvage chemotherapy in the platinum-refractory setting. Pembrolizumab has the highest level of evidence in platinum-refractory aUC, whereas pembrolizumab and atezolizumab have comparable level of evidence in the frontline setting in cisplatin-ineligible patients. Ongoing research is evaluating novel agents, various rational combinations, and sequences, as well as predictive and prognostic biomarkers.

  7. Current Status and Prospects of Gene Therapy for the Inner Ear

    PubMed Central

    Huang, Aji

    2011-01-01

    Abstract Inner ear diseases are common and often result in hearing disability. Sensorineural hearing loss is the main cause of hearing disability. So far, no effective treatment is available although some patients may benefit from a hearing aid equipped with a hearing amplifier or from cochlear implantation. Inner ear gene therapy has become an emerging field of study for the treatment of hearing disability. Numerous new discoveries and tremendous advances have been made in inner ear gene therapy including gene vectors, routes of administration, and therapeutic genes and targets. Gene therapy may become a treatment option for inner ear diseases in the near future. In this review, we summarize the current state of inner ear gene therapy including gene vectors, delivery routes, and therapeutic genes and targets by examining and analyzing publications on inner ear gene therapy from the literature and patent documents, and identify promising patents, novel techniques, and vital research projects. We also discuss the progress and prospects of inner ear gene therapy, the advances and shortcomings, with possible solutions in this field of research. PMID:21338273

  8. Combination Therapy with Capecitabine and Cisplatin as Second-Line Chemotherapy for Advanced Biliary Tract Cancer.

    PubMed

    Jung, Jang Han; Lee, Hee Seung; Jo, Jung Hyun; Cho, In Rae; Chung, Moon Jae; Bang, Seungmin; Park, Seung Woo; Song, Si Young; Park, Jeong Youp

    2017-01-01

    Palliative chemotherapy is the main treatment for advanced biliary tract cancer (BTC). However, there is a lack of established second-line chemotherapy to treat disease progression after first-line chemotherapy. We examined combination therapy with capecitabine and cisplatin for advanced BTC as a second-line regimen. We analyzed the medical records of 40 patients diagnosed with BTC who received palliative second-line chemotherapy with capecitabine and cisplatin. The median overall survival from the start of second-line chemotherapy was 6.3 months. The median overall survival from diagnosis was 17.9 months. The median progression-free survival during second-line chemotherapy was 2.3 months. Nine (30%) patients experienced adverse events of grade ≥3. Eastern Cooperative Oncology Group performance score was an independent predictor of adverse events. Combination therapy with capecitabine and cisplatin may be an option for second-line chemotherapy in some of patients with advanced BTC. © 2017 S. Karger AG, Basel.

  9. Positioning Bascularized Composite Allotransplantation with the Spectrum of Transplantion

    DTIC Science & Technology

    2015-10-01

    therapeutic option for patients in need of advanced tissue reconstruction. II. Keywords Biorepository, vascularized composite allograft , nonhuman primates... tissues (e.g. hand, face) into a useful therapeutic option for individuals in need of advance tissue reconstruction and replacement. The proposal...death but increased the rate of soft tissue injury. Vascularized composite allotransplantation (VCA) has recently emerged as a promising strategy for

  10. Analysis of edible oil processing options for the BIO-Plex advanced life support system

    NASA Technical Reports Server (NTRS)

    Greenwalt, C. J.; Hunter, J.

    2000-01-01

    Edible oil is a critical component of the proposed plant-based Advanced Life Support (ALS) diet. Soybean, peanut, and single-cell oil are the oil source options to date. In terrestrial manufacture, oil is ordinarily extracted with hexane, an organic solvent. However, exposed solvents are not permitted in the spacecraft environment or in enclosed human tests by National Aeronautics and Space Administration due to their potential danger and handling difficulty. As a result, alternative oil-processing methods will need to be utilized. Preparation and recovery options include traditional dehulling, crushing, conditioning, and flaking, extrusion, pressing, water extraction, and supercritical extraction. These processing options were evaluated on criteria appropriate to the Advanced Life Support System and BIO-Plex application including: product quality, product stability, waste production, risk, energy needs, labor requirements, utilization of nonrenewable resources, usefulness of by-products, and versatility and mass of equipment to determine the most appropriate ALS edible oil-processing operation.

  11. Immunotherapy in head and neck cancer - scientific rationale, current treatment options and future directions.

    PubMed

    Rothschild, Uta; Muller, Laurent; Lechner, Axel; Schlösser, Hans A; Beutner, Dirk; Läubli, Heinz; Zippelius, Alfred; Rothschild, Sacha I

    2018-05-14

    Head and neck squamous cell carcinoma (HNSCC) is a frequent tumour arising from multiple anatomical subsites in the head and neck region. The treatment for early-stage disease is generally single modality, either surgery or radiotherapy. The treatment for locally advanced tumours is multimodal. For recurrent/metastatic HNSCC palliative chemotherapy is standard of care. The prognosis is limited and novel treatment approaches are urgently needed. HNSCC evades immune responses through multiple resistance mechanisms. HNSCC is particularly characterised by an immunosuppressive environment which includes the release of immunosuppressive factors, activation, expansion of immune cells with inhibitory activity and decreased tumour immunogenicity. An in-depth understanding of these mechanisms led to rational design of immunotherapeutic approaches and clinical trials. Currently, only immune checkpoint inhibitors, namely monoclonal antibodies targeting the immune inhibitory receptor programmed cell death 1 (PD-1) and its ligand PD-L1 have proven clinical efficacy in randomised phase III trials. The PD-1 inhibitor nivolumab is the only drug approved for platinum-refractory recurrent/metastatic HNSCC. However, many more immunotherapeutic treatment options are currently under investigation. Ongoing trials are investigating immunotherapeutic approaches also in the curative setting and combination therapies using different immunotherapeutic approaches. This review article summarises current knowledge of the role of the immune system in the development and progression of HNSCC, and provides a comprehensive overview on the development of immunotherapeutic approaches.

  12. Treatment Options for Narcolepsy.

    PubMed

    Barateau, Lucie; Lopez, Régis; Dauvilliers, Yves

    2016-05-01

    Narcolepsy type 1 and narcolepsy type 2 are central disorders of hypersomnolence. Narcolepsy type 1 is characterized by excessive daytime sleepiness and cataplexy and is associated with hypocretin-1 deficiency. On the other hand, in narcolepsy type 2, cerebrospinal fluid hypocretin-1 levels are normal and cataplexy absent. Despite major advances in our understanding of narcolepsy mechanisms, its current management is only symptomatic. Treatment options may vary from a single drug that targets several symptoms, or multiple medications that each treats a specific symptom. In recent years, narcolepsy treatment has changed with the widespread use of modafinil/armodafinil for daytime sleepiness, antidepressants (selective serotonin and dual serotonin and noradrenalin reuptake inhibitors) for cataplexy, and sodium oxybate for both symptoms. Other psychostimulants can also be used, such as methylphenidate, pitolisant and rarely amphetamines, as third-line therapy. Importantly, clinically relevant subjective and objective measures of daytime sleepiness are required to monitor the treatment efficacy and to provide guidance on whether the treatment goals are met. Associated symptoms and comorbid conditions, such as hypnagogic/hypnopompic hallucinations, sleep paralysis, disturbed nighttime sleep, unpleasant dreams, REM- and non REM-related parasomnias, depressive symptoms, overweight/obesity, and obstructive sleep apnea, should also be taken into account and managed, if required. In the near future, the efficacy of new wake-promoting drugs, anticataplectic agents, hypocretin replacement therapy and immunotherapy at the early stages of the disease should also be evaluated.

  13. Assessment and management of refractory breathlessness in interstitial lung disease.

    PubMed

    Speakman, Lucy; Walthall, Helen

    2017-09-02

    Interstitial lung disease (ILD) refers to a cluster of fibroinflammatory conditions. There are limited treatment options and most patients have severe dyspnoea. The prognosis is poor. This study aims to evaluate current literature on the assessment and management of refractory breathlessness in ILD. Few tools are available to assess dyspnoea in advanced respiratory disease. Holistic assessment requires a combination of tools but there are few disease specific tools. The role of opioids is well established in the reduction of breathlessness, but there is insufficient evidence that benzodiazepines are beneficial. Non-pharmcolological breathlessness intervention services can give patients mastery of their disease, reduced distress due to breathlessness and were more cost effective. More research on holistic interventions for use in advanced disease needs to be done. Patient-reported outcome measures could elicit valuable evidence to describe the benefit of breathlessness management services in advanced respiratory disease.

  14. Therapeutic Potential of Curcumin in Treatment of Pancreatic Cancer: Current Status and Future Perspectives.

    PubMed

    Hosseini, Mina; Hassanian, Seyed Mahdi; Mohammadzadeh, Elham; ShahidSales, Soodabeh; Maftouh, Mina; Fayazbakhsh, Hasan; Khazaei, Majid; Avan, Amir

    2017-07-01

    Pancreatic cancer is among the leading cause of deaths due to cancer with extremely poor prognosis. Gemcitabine is being used in the treatment of patient with pancreatic ductal adenocarcinoma (PDAC), although, the response rate is bellow 12%. A recent phase III trial revealed that FOLFIRINOX could be an option for the treatment of metastatic PDAC patients, although it is associated with increased toxicity. Therefore, identification of novel agents that either improves gemcitabine activity, within novel combinatorial approaches, or with a better efficacy than gemcitabine is warranted. The antitumor activity of curcumin in several tumors, including prostate, breast and colorectal cancers have investigated. A recent phase II trial explored the effects of curcumin in advanced pancreatic cancer patient. They found that oral curcumin was well tolerated. Another trial showed the activity of 8,000 mg of curcumin in combination with gemcitabine in patients with advanced pancreatic cancer. This review summarizes the current knowledge about possible molecular mechanisms of curcumin in PDAC with particular emphasis on preclinical/clinical studies in pancreatic cancer treatment. J. Cell. Biochem. 118: 1634-1638, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Treating children with inflammatory bowel disease: Current and new perspectives

    PubMed Central

    Guariso, Graziella; Gasparetto, Marco

    2017-01-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gut characterised by alternating periods of remission and relapse. Whilst the mechanism underlying this disease is yet to be fully understood, old and newer generation treatments can only target selected pathways of this complex inflammatory process. This narrative review aims to provide an update on the most recent advances in treatment of paediatric IBD. A MEDLINE search was conducted using “paediatric inflammatory bowel disease”, “paediatric Crohn’s disease”, “paediatric ulcerative colitis”, “treatment”, “therapy”, “immunosuppressant”, “biologic”, “monitoring” and “biomarkers” as key words. Clinical trials, systematic reviews, and meta-analyses published between 2014 and 2016 were selected. Studies referring to earlier periods were also considered in case the data was relevant to our scope. Major advances have been achieved in monitoring the individual metabolism, toxicity and response to relevant medications in IBD including thiopurines and biologics. New biologics acting on novel mechanisms such as selective interference with lymphocyte trafficking are emerging treatment options. Current research is investing in the development of reliable prognostic biomarkers, aiming to move towards personalised treatments targeted to individual patients. PMID:28852307

  16. 78 FR 8060 - Treatment of Grantor of an Option on a Partnership Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-05

    ... Treatment of Grantor of an Option on a Partnership Interest AGENCY: Internal Revenue Service (IRS), Treasury... the tax treatment of noncompensatory options and convertible instruments issued by a partnership... with respect to, or a lapse of, an option on a partnership interest. The proposed regulations will...

  17. Current diagnosis and treatment of benign biliary strictures after living donor liver transplantation

    PubMed Central

    Chang, Jae Hyuck; Lee, Inseok; Choi, Myung-Gyu; Han, Sok Won

    2016-01-01

    Despite advances in surgical techniques, benign biliary strictures after living donor liver transplantation (LDLT) remain a significant biliary complication and play an important role in graft and patient survival. Benign biliary strictures after transplantation are classified into anastomotic or non-anastomotic strictures. These two types differ in presentation, outcome, and response to therapy. The leading causes of biliary strictures include impaired blood supply, technical errors during surgery, and biliary anomalies. Because patients usually have non-specific symptoms, a high index of suspicion should be maintained. Magnetic resonance cholangiography has gained widespread acceptance as a reliable noninvasive tool for detecting biliary complications. Endoscopy has played an increasingly prominent role in the diagnosis and treatment of biliary strictures after LDLT. Endoscopic management in LDLT recipients may be more challenging than in deceased donor liver transplantation patients because of the complex nature of the duct-to-duct reconstruction. Repeated aggressive endoscopic treatment with dilation and the placement of multiple plastic stents is considered the first-line treatment for biliary strictures. Percutaneous and surgical treatments are now reserved for patients for whom endoscopic management fails and for those with multiple, inaccessible intrahepatic strictures or Roux-en-Y anastomoses. Recent advances in enteroscopy enable treatment, even in these latter cases. Direct cholangioscopy, another advanced form of endoscopy, allows direct visualization of the inner wall of the biliary tree and is expected to facilitate stenting or stone extraction. Rendezvous techniques can be a good option when the endoscopic approach to the biliary stricture is unfeasible. These developments have resulted in almost all patients being managed by the endoscopic approach. PMID:26819525

  18. Recent advances in the risk factors, diagnosis and management of Epstein-Barr virus post-transplant lymphoproliferative disease.

    PubMed

    Aguayo-Hiraldo, Paibel; Arasaratnam, Reuben; Rouce, Rayne H

    Fifty years after the first reports of Epstein-Barr virus (EBV)-associated endemic Burkitt's lymphoma, EBV has emerged as the third most prevalent oncogenic virus worldwide. EBV infection is associated with various malignancies including Hodgkin and non-Hodgkin lymphoma, NK/T-cell lymphoma and nasopharyngeal carcinoma. Despite the highly specific immunologic control in the immunocompetent host, EBV can cause severe complications in the immunocompromised host (namely, post-transplant lymphoproliferative disease). This is particularly a problem in patients with delayed immune reconstitution post-hematopoietic stem cell transplant or solid organ transplant. Despite advances in diagnostic techniques and treatment algorithms allowing earlier identification and treatment of patients at highest risk, mortality rates remain as high as 90% if not treated early. The cornerstones of treatment include reduction in immunosuppression and in vivo B cell depletion with an anti-CD20 monoclonal antibody. However, these treatment modalities are not always feasible due to graft rejection, emergence of graft vs. host disease, and toxicity. Newer treatment modalities include the use of adoptive T cell therapy, which has shown promising results in various EBV-related malignancies. In this article we will review recent advances in risk factors, diagnosis and management of EBV-associated malignancies, particularly post-transplant lymphoproliferative disease. We will also discuss new and innovative treatment options including adoptive T cell therapy as well as management of special situations such as chronic active EBV and EBV-associated hemophagocytic lymphohistiocytosis. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  19. Experimental Therapy of Advanced Breast Cancer: Targeting NFAT1-MDM2-p53 Pathway.

    PubMed

    Qin, Jiang-Jiang; Wang, Wei; Zhang, Ruiwen

    2017-01-01

    Advanced breast cancer, especially advanced triple-negative breast cancer, is typically more aggressive and more difficult to treat than other breast cancer phenotypes. There is currently no curable option for breast cancer patients with advanced diseases, highlighting the urgent need for novel treatment strategies. We have recently discovered that the nuclear factor of activated T cells 1 (NFAT1) activates the murine double minute 2 (MDM2) oncogene. Both MDM2 and NFAT1 are overexpressed and constitutively activated in breast cancer, particularly in advanced breast cancer, and contribute to its initiation, progression, and metastasis. MDM2 regulates cancer cell proliferation, cell cycle progression, apoptosis, migration, and invasion through both p53-dependent and -independent mechanisms. We have proposed to target the NFAT1-MDM2-p53 pathway for the treatment of human cancers, especially breast cancer. We have recently identified NFAT1 and MDM2 dual inhibitors that have shown excellent in vitro and in vivo activities against breast cancer, including triple-negative breast cancer. Herein, we summarize recent advances made in the understanding of the oncogenic functions of MDM2 and NFAT1 in breast cancer, as well as current targeting strategies and representative inhibitors. We also propose several strategies for inhibiting the NFAT1-MDM2-p53 pathway, which could be useful for developing more specific and effective inhibitors for breast cancer therapy. Copyright © 2017. Published by Elsevier Inc.

  20. A Protocol-Based Decision for Choosing a Proper Surgical Treatment Option for Carotid Artery Stenosis.

    PubMed

    Jang, E-Wook; Chung, Joonho; Seo, Kwon-Duk; Suh, Sang Hyun; Kim, Yong Bae; Lee, Kyung-Yul

    2015-06-01

    There are two established surgical treatment options for carotid artery stenosis. Carotid endarterectomy (CEA) has been accepted as a gold standard for surgical treatment while carotid artery stenting (CAS) has recently become an alternative option. Each treatment option has advantages and disadvantages for the treatment outcomes. We propose a protocol for selection of a proper surgical treatment option for carotid artery stenosis. A total of 192 published articles on management of carotid artery stenosis were reviewed. Preoperatively considerable factors which had been repeatedly noted in those articles for the risk/benefits of CEA or CAS were selected. According to those factors, a protocol with four categories was established. CEA or CAS is indicated when the patient has a symptomatic stenosis ≥ 50%, or when the patient has an asymptomatic stenosis ≥ 80%. Each treatment option has absolute indications and favorable indications. Each absolute indication is scored with three points, and each favorable indication, one point. Based on the highest scores, a proper treatment option (CEA or CAS) is selected. We have been treating patients according to this protocol and evaluating the outcomes of our protocol-based decision because this protocol might be helpful in assessment of risk/benefit for selection of a proper surgical treatment option in patients with carotid artery stenosis.

  1. Current treatment for vitreous floaters.

    PubMed

    Sendrowski, David P; Bronstein, Mark A

    2010-03-01

    Vitreous floaters are a common complaint in the ophthalmic care setting. Patients seek explanation and advice regarding possible treatment options. Because the condition is considered benign, ophthalmic care practitioners have little to offer regarding treatment options. The majority of cases encountered are managed with patient education and reassurance. Although almost all patients accept the conservative management option, there is a small subset of patients who may desire a more aggressive treatment intervention for resolution of their visual symptoms. Information with regard to treatment options is readily available to patients through Internet searches and non-peer reviewed educational Web sites. The risks and benefits for these treatment options are not fully covered. Management of floaters should include education regarding "off-label" procedures as well as discussion about benefits and risks associated with such treatment options. It is vital that eye care practitioners advise and counsel patients with symptomatic floaters for optimum ocular health care. This article reviews the current conventional and "off-label" treatment options for symptomatic patients with vitreous floaters. Copyright (c) 2010 American Optometric Association. Published by Elsevier Inc. All rights reserved.

  2. Advances in Imaging and Management Trends of Traumatic Aortic Injuries

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nagpal, Prashant, E-mail: drprashantnagpal@gmail.com, E-mail: Prashant-nagpal@uiowa.edu; Mullan, Brian F.; Sen, Indrani

    Acute traumatic aortic injury (ATAI) is a life-threatening injury. CT is the imaging tool of choice, and the knowledge of direct and indirect signs of injury, grading system, and current management protocol helps the emergency radiologist to better identify and classify the injury and provide additional details that can impact management options. Newer dual-source CT technology with ultrafast acquisition speed has also influenced the appropriate protocol for imaging in patients with suspected ATAI. This review highlights the imaging protocol in patients with blunt trauma, CT appearance and grading systems of ATAI, management options, and the role of the multidisciplinary teammore » in the management of these patients. We also briefly review the current literature on the definition, treatment, and follow-up protocol in patients with minimal aortic injury.« less

  3. Complications in implant dentistry

    PubMed Central

    Hanif, Ayesha; Qureshi, Saima; Sheikh, Zeeshan; Rashid, Haroon

    2017-01-01

    After tooth loss, an individual may seek tooth replacement so that his/her function and esthetics could be restored. Clinical prosthodontics, during the past decade, has significantly improved and developed according to the advancements in the science and patient's demands and needs. Conventional options in prosthodontics for substituting a missing single tooth include the removable partial denture, partial and full coverage bridgework, and resin-bonded bridgework. Dental implants have gained increasing popularity over the years as they are capable of restoring the function to near normal in both partial and completely edentulous arches. With substantial evidence available, fixed implant-supported prosthesis are fully acknowledged as a reliable treatment option for the replacement of single or multiple missing teeth nowadays. While dental implants are increasingly becoming the choice of replacement for missing teeth, the impediments associated with them are progressively emerging too. PMID:28435381

  4. FDA Approval Summary: Atezolizumab for the Treatment of Patients with Progressive Advanced Urothelial Carcinoma after Platinum‐Containing Chemotherapy

    PubMed Central

    Suzman, Daniel; Maher, V. Ellen; Zhang, Lijun; Tang, Shenghui; Ricks, Tiffany; Palmby, Todd; Fu, Wentao; Liu, Qi; Goldberg, Kirsten B.; Kim, Geoffrey; Pazdur, Richard

    2017-01-01

    Abstract Until recently in the United States, no products were approved for second‐line treatment of advanced urothelial carcinoma. On May 18, 2016, the U.S. Food and Drug Administration approved atezolizumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease progressed during or following platinum‐containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum‐containing chemotherapy. Atezolizumab is a programmed death‐ligand 1 (PD‐L1) blocking antibody and represents the first approved product directed against PD‐L1. This accelerated approval was based on results of a single‐arm trial in 310 patients with locally advanced or metastatic urothelial carcinoma who had disease progression after prior platinum‐containing chemotherapy. Patients received atezolizumab 1,200 mg intravenously every 3 weeks until disease progression or unacceptable toxicity. Key efficacy measures were objective response rate (ORR), as assessed by Independent Review per RECIST 1.1, and duration of response (DoR). With a median follow‐up of 14.4 months, confirmed ORR was 14.8% (95% CI: 11.1, 19.3) in all treated patients. Median DoR was not reached and response durations ranged from 2.1+ to 13.8+ months. Of the 46 responders, 37 patients had an ongoing response for ≥ 6 months. The most common adverse reactions (≥20%) were fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, and constipation. Infection and immune‐related adverse events also occurred, including pneumonitis, hepatitis, colitis, endocrine disorders, and rashes. Overall, the benefit‐risk assessment was favorable to support accelerated approval. The observed clinical benefits need to be verified in confirmatory trial(s). Implications for Practice. This accelerated approval of atezolizumab for second‐line use in advanced urothelial carcinoma provides patients with an effective, novel treatment option for the management of their disease. This represents the first immunotherapy approved in this disease setting. PMID:28424325

  5. The value of oral appliances in the treatment of obstructive sleep apnoea

    PubMed Central

    Rose, Edmund Clemens

    2006-01-01

    Oral appliances have long been used to treat snoring and mild to moderate obstructive sleep apnoea. This kind of treatment is considered an alternative, non-invasive treatment option. Mandibular protrusive appliances enlarge and stabilise the oro- and hypo-pharyngeal airway space by advancing the mandible, and stretching the attached soft tissue, in particular the tongue, soft palate, uvula, and the pharyngeal tissues. This article summarises the indications, contraindications, and possible side-effects of using oral appliances. Therapeutic efficacy is influenced by multiple parameters that are clinically difficult to control. One major parameter is the patient`s stomatognathic situation of the patient. Thus oral appliances are restricted to patients whose dental retention is adequate for permanent treatment and who do not suffer from temporomandibular joint dysfunction. Regular follow-up sleep studies and dental evaluations are necessary to ensure adequate permanent treatment. PMID:22073072

  6. What progress has been made in the understanding and treatment of degenerative lumbosacral stenosis in dogs during the past 30 years?

    PubMed

    Jeffery, Nick D; Barker, Andrew; Harcourt-Brown, Tom

    2014-07-01

    An association between degenerative changes in the lumbosacral region of the vertebral column and clinical signs of pain and pelvic limb dysfunction has long been recognized in dogs and has become known as degenerative lumbosacral stenosis syndrome. Over the past two decades, methods of imaging this condition have advanced greatly, but definitive criteria for a reliable diagnosis using physical examination, imaging and electrodiagnostics remain elusive. Available treatment options have changed little over more than 30 years but, more importantly, there is a lack of comparative studies and little progress has been made in providing evidence-based recommendations for the treatment of affected dogs. This review provides an overview of the changes in diagnosis, understanding and treatment of lumbosacral disease in dogs over the past 30 years. Approaches to address the unanswered questions regarding treatment choice are also proposed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Treatment success with titratable thermoplastic mandibular advancement devices for obstructive sleep apnea: A comparison of patient characteristics.

    PubMed

    Wang, Tang-Chuan; Tsou, Yung-An; Wu, Yi-Fan; Huang, Chia-Chang; Lin, Wesley Wen-Yang; Li, Yu-Fen; Chen, Michael Yuan-Chien; Tai, Chih-Jaan; Tsai, Ming-Hsui

    2017-03-01

    A titratable thermoplastic mandibular advancement device (MAD) is clearly an effective treatment option in some patients with obstructive sleep apnea (OSA). Determining which patients may be more likely to respond to treatment with thermoplastic MADs and to adhere to treatment would be of obvious clinical relevance. This was an experimental descriptive study (N = 60). Patients with OSA were instructed to wear a titratable thermoplastic MAD for 3 months. Treatment success was defined as a ≥50% reduction from baseline in the apnea-hypopnea index (AHI) or AHI <10 when wearing MAD. Adherence was defined as MAD use ≥5 nights/week. Treatment was successful in 66.7% of patients and 60.0% were adherent. All polysomnographic parameters and visual analogue scale scores (sleep quality, snoring, waking refreshed) were significantly improved after treatment. The patients in whom treatment failed had significantly higher neck circumferences (39.3 cm vs. 37.5 cm, p = 0.014), higher baseline AHI values (26.6 vs. 18.0, p = 0.016), and smaller AHI reduction (-31.8 vs -53.1, p < 0.001) than those in the group in whom treatment succeeded. There were no significant differences in polysomnographic, cephalometric, or visual analogue scale measures between patients for whom treatment was and was not successful, regardless of baseline values or the change rates after the MAD was placed. Titratable thermoplastic MADs can improve indicators of sleep quality, even in patients in whom treatment is considered to have failed.

  8. Locally advanced vulva cancer: A single centre review of anovulvectomy and a systematic review of surgical, chemotherapy and radiotherapy alternatives. Is an international collaborative RCT destined for the "too difficult to do" box?

    PubMed

    O'Donnell, Rachel Louise; Verleye, Leen; Ratnavelu, Nithya; Galaal, Khadra; Fisher, Ann; Naik, Raj

    2017-02-01

    Treatment of locally advanced vulva cancer (LAVC) remains challenging. Due to the lack of randomised trials many questions regarding the indications for different treatment options and their efficacy remain unanswered. In this retrospective study we provide the largest published series of LAVC patients treated with anovulvectomy, reporting oncological outcomes and morbidity. Additionally, a systematic literature review was performed for all treatment options 1946-2015. In our case series, 57/70 (81%) patients were treated in the primary setting with anovulvectomy and 13 patients underwent anovulvectomy for recurrent disease. The median overall survival (OS) was 69months (1-336) with disease specific survival of 159months (1-336). Following anovulvectomy for primary disease, time to progression and OS were significantly higher in node negative disease (10 vs. 96months; 19 vs. 121months, p<0.0001). Post-surgical complications were observed in 36 (51.4%), the majority of which were Grade I/II infections. There was one peri-operative death. Review of the literature showed that chemotherapy, radiotherapy or combination treatments are alternatives to surgery. Evidence relating to all of these consisted mostly of small retrospective series, which varied considerably in terms of patient characteristics and treatment schedules. Significant patient and treatment heterogeneity prevented meta-analysis with significant biases in these studies. It was unclear if survival or morbidity was better in any one group with a lack of data reporting complications, quality of life, and long term follow-up. However, results for chemoradiation are encouraging enough to warrant further investigation. There remains inadequate evidence to identify an optimal treatment for LAVC. However, there is sufficient evidence to support a trial of anovulvectomy versus chemoradiation. Discussions and consensus would be needed to determine trial criteria including the primary outcome measure. Neoadjuvant chemotherapy or radiotherapy alone may be best reserved for the palliative setting or metastatic disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Cost-effectiveness of nitrogen mitigation by alternative household wastewater management technologies.

    PubMed

    Wood, Alison; Blackhurst, Michael; Hawkins, Troy; Xue, Xiaobo; Ashbolt, Nicholas; Garland, Jay

    2015-03-01

    Household wastewater, especially from conventional septic systems, is a major contributor to nitrogen pollution. Alternative household wastewater management technologies provide similar sewerage management services but their life cycle costs and nitrogen flow implications remain uncertain. This paper addresses two key questions: (1) what are the total costs, nitrogen mitigation potential, and cost-effectiveness of a range of conventional and alternative municipal wastewater treatment technologies, and (2) what uncertainties influence these outcomes and how can we improve our understanding of these technologies? We estimate a household nitrogen mass balance for various household wastewater treatment systems and combine this mass balance with life cycle cost assessment to calculate the cost-effectiveness of nitrogen mitigation, which we define as nitrogen removed from the local watershed. We apply our methods to Falmouth, MA, where failing septic systems have caused heightened eutrophication in local receiving water bodies. We find that flushing and dry (composting) urine-diversion toilets paired with conventional septic systems for greywater management demonstrate the lowest life cycle cost and highest cost-effectiveness (dollars per kilogram of nitrogen removed from the watershed). Composting toilets are also attractive options in some cases, particularly best-case nitrogen mitigation. Innovative/advanced septic systems designed for high-level nitrogen removal are cost-competitive options for newly constructed homes, except at their most expensive. A centralized wastewater treatment plant is the most expensive and least cost-effective option in all cases. Using a greywater recycling system with any treatment technology increases the cost without adding any nitrogen removal benefits. Sensitivity analysis shows that these results are robust considering a range of cases and uncertainties. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Wrist osteoarthritis.

    PubMed

    Laulan, J; Marteau, E; Bacle, G

    2015-02-01

    Painful wrist osteoarthritis can result in major functional impairment. Most cases are related to posttraumatic sequel, metabolic arthropathies, or inflammatory joint disease, although wrist osteoarthritis occurs as an idiopathic condition in a small minority of cases. Surgery is indicated only when conservative treatment fails. The main objective is to ensure pain relief while restoring strength. Motion-preserving procedures are usually preferred, although residual wrist mobility is not crucial to good function. The vast array of available surgical techniques includes excisional arthroplasty, limited and total fusion, total wrist denervation, partial and total arthroplasty, and rib-cartilage graft implantation. Surgical decisions rest on the cause and extent of the degenerative wrist lesions, degree of residual mobility, and patient's wishes and functional demand. Proximal row carpectomy and four-corner fusion with scaphoid bone excision are the most widely used surgical procedures for stage II wrist osteoarthritis secondary to scapho-lunate advanced collapse (SLAC) or scaphoid non-union advanced collapse (SNAC) wrist. Proximal row carpectomy is not indicated in patients with stage III disease. Total wrist denervation is a satisfactory treatment option in patients of any age who have good range of motion and low functional demands; furthermore, the low morbidity associated with this procedure makes it a good option for elderly patients regardless of their range of motion. Total wrist fusion can be used not only as a revision procedure, but also as the primary surgical treatment in heavy manual labourers with wrist stiffness or generalised wrist-joint involvement. The role for pyrocarbon implants, rib-cartilage graft implantation, and total wrist arthroplasty remains to be determined, given the short follow-ups in available studies. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  11. Evidence-Based Treatment Options in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

    PubMed Central

    Argiris, Athanassios; Harrington, Kevin J.; Tahara, Makoto; Schulten, Jeltje; Chomette, Pauline; Ferreira Castro, Ana; Licitra, Lisa

    2017-01-01

    The major development of the past decade in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) was the introduction of cetuximab in combination with platinum plus 5-fluorouracil chemotherapy (CT), followed by maintenance cetuximab (the “EXTREME” regimen). This regimen is supported by a phase 3 randomized trial and subsequent observational studies, and it confers well-documented survival benefits, with median survival ranging between approximately 10 and 14 months, overall response rates between 36 and 44%, and disease control rates of over 80%. Furthermore, as indicated by patient-reported outcome measures, the addition of cetuximab to platinum-based CT leads to a significant reduction in pain and problems with social eating and speech. Conversely, until very recently, there has been a lack of evidence-based second-line treatment options, and the therapies that have been available have shown low response rates and poor survival outcomes. Presently, a promising new treatment option in R/M SCCHN has emerged: immune checkpoint inhibitors (ICIs), which have demonstrated favorable results in second-line clinical trials. Nivolumab and pembrolizumab are the first two ICIs that were approved by the US Food and Drug Administration. We note that the trials that showed benefit with ICIs included not only patients who previously received ≥1 platinum-based regimens for R/M SCCHN but also patients who experienced recurrence within 6 months after combined modality therapy with a platinum agent for locally advanced disease. In this review, we outline the available clinical and observational evidence for the EXTREME regimen and the initial results from clinical trials for ICIs in patients with R/M SCCHN. We propose that these treatment options can be integrated into a new continuum of care paradigm, with first-line EXTREME regimen followed by second-line ICIs. A number of ongoing clinical trials are comparing regimens with ICIs, alone and in combination with other ICIs or CT, with the EXTREME regimen for first-line treatment of R/M SCCHN. As we eagerly await the results of these trials, the EXTREME regimen remains the standard of care for the first-line treatment of R/M SCCHN. PMID:28536670

  12. Advanced reproductive age and fertility.

    PubMed

    Liu, Kimberly; Case, Allison

    2011-11-01

    To improve awareness of the natural age-related decline in female and male fertility with respect to natural fertility and assisted reproductive technologies (ART) and provide recommendations for their management, and to review investigations in the assessment of ovarian aging. This guideline reviews options for the assessment of ovarian reserve and fertility treatments using ART with women of advanced reproductive age presenting with infertility. The outcomes measured are the predictive value of ovarian reserve testing and pregnancy rates with natural and assisted fertility. Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in June 2010, using appropriate key words (ovarian aging, ovarian reserve, advanced maternal age, advanced paternal age, ART). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated into the guideline to December 2010. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table). Primary and specialist health care providers and women will be better informed about ovarian aging and the age-related decline in natural fertility and about options for assisted reproductive technology. 1. Women in their 20s and 30s should be counselled about the age-related risk of infertility when other reproductive health issues, such as sexual health or contraception, are addressed as part of their primary well-woman care. Reproductive-age women should be aware that natural fertility and assisted reproductive technology success (except with egg donation) is significantly lower for women in their late 30s and 40s. (II-2A) 2. Because of the decline in fertility and the increased time to conception that occurs after the age of 35, women > 35 years of age should be referred for infertility work-up after 6 months of trying to conceive. (III-B) 3. Ovarian reserve testing may be considered for women ≥ 35 years of age or for women < 35 years of age with risk factors for decreased ovarian reserve, such as a single ovary, previous ovarian surgery, poor response to follicle-stimulating hormone, previous exposure to chemotherapy or radiation, or unexplained infertility. (III-B) 4. Ovarian reserve testing prior to assisted reproductive technology treatment may be used for counselling but has a poor predictive value for non-pregnancy and should be used to exclude women from treatment only if levels are significantly abnormal. (II-2A) 5. Pregnancy rates for controlled ovarian hyperstimulation are low for women > 40 years of age. Women > 40 years should consider IVF if they do not conceive within 1 to 2 cycles of controlled ovarian hyperstimulation. (II-2B) 6. The only effective treatment for ovarian aging is oocyte donation. A woman with decreased ovarian reserve should be offered oocyte donation as an option, as pregnancy rates associated with this treatment are significantly higher than those associated with controlled ovarian hyperstimulation or in vitro fertilization with a woman's own eggs. (II-2B) 7. Women should be informed that the risk of spontaneous pregnancy loss and chromosomal abnormalities increases with age. Women should be counselled about and offered appropriate prenatal screening once pregnancy is established. (II-2A) 8. Pre-conception counselling regarding the risks of pregnancy with advanced maternal age, promotion of optimal health and weight, and screening for concurrent medical conditions such as hypertension and diabetes should be considered for women > age 40. (III-B) 9. Advanced paternal age appears to be associated with an increased risk of spontaneous abortion and increased frequency of some autosomal dominant conditions, autism spectrum disorders, and schizophrenia. Men > age 40 and their partners should be counselled about these potential risks when they are seeking pregnancy, although the risks remain small. (II-2C).

  13. Contemporary surgical devices for male stress urinary incontinence: a review of technological advances in current continence surgery.

    PubMed

    Chung, Eric

    2017-07-01

    Male stress urinary incontinence (SUI) remains a debilitating condition that adversely impacts all domains of quality of life and is associated with significant social stigma and health economic burden. The incidence of post-prostatectomy urinary incontinence (PPI) depends on the definition of urinary incontinence and the length of patient follow up. In patients with persistent PPI following failure of conservative measures, surgical treatment is recommended although there is no published guideline on when surgery should be performed, and what the best surgical option is. Male slings (MS) can be divided into adjustable or non-adjustable types, and offers an attractive option for patients who wish to avoid mechanical handling during urinary voiding. Published intermediate data supports good safety and efficacy rate in men with mild to moderate degree of SUI. The AMS 800 artificial urinary sphincter (AUS) remains the standard of treatment for complete continence and has the longest efficacy and safety records. Other AUS-like devices are designed to address current AMS 800 limitations but themselves are fraught with their own issues.

  14. Studies on nonsense mediated decay reveal novel therapeutic options for genetic diseases.

    PubMed

    Bashyam, Murali D

    2009-01-01

    Scientific breakthroughs have often led to commercially viable patents mainly in the field of engineering. Commercialization in the field of medicine has been restricted mostly to machinery and engineering on the one hand and therapeutic drugs for common chronic ailments such as cough, cold, headache, etc, on the other. Sequencing of the human genome has attracted the attention of pharmaceutical companies and now biotechnology has become a goldmine for commercialization of products and processes. Recent advances in our understanding of basic biological processes have resulted in the opening of new avenues for treatment of human genetic diseases, especially single gene disorders. A significant proportion of human genetic disorders have been shown to be caused due to degradation of transcripts for specific genes through a process called nonsense mediated decay (NMD). The modulation of NMD provides a viable therapeutic option for treatment of several genetic disorders and therefore has been a good prospect for patenting and commercialization. In this review the molecular basis for NMD and attempts to treat genetic diseases which result from NMD are discussed.

  15. Post-Stroke Sleep-Disordered Breathing—Pathophysiology and Therapy Options

    PubMed Central

    Stevens, David; Martins, Rodrigo Tomazini; Mukherjee, Sutapa; Vakulin, Andrew

    2018-01-01

    Sleep-disordered breathing (SDB), encompassing both obstructive and central sleep apnea, is prevalent in at least 50% of stroke patients. Small studies have shown vast improvements in post-stroke functional recovery outcomes after the treatment of SDB by continuous positive airway pressure. However, compliance to this therapy is very poor in this complex patient group. There are alternative therapy options for SDB that may be more amenable for use in at least some post-stroke patients, including mandibular advancement, supine avoidance, and oxygen therapy. There are few studies, however, that demonstrate efficacy and compliance with these alternative therapies currently. Furthermore, novel SDB-phenotyping approaches may help to provide important clinical information to direct therapy selection in individual patients. Prior to realizing individualized therapy, we need a better understanding of the pathophysiology of SDB in post-stroke patients, including the role of inherent phenotypic traits, as well as the contribution of stroke size and location. This review summarizes the available literature on SDB pathophysiology and treatment in post-stroke patients, identifies gaps in the literature, and sets out areas for further research. PMID:29536012

  16. Intersection of Cardiovascular Disease and Kidney Disease: Atrial Fibrillation

    PubMed Central

    Bansal, Nisha; Hsu, Chi-yuan; Go, Alan S.

    2014-01-01

    Purpose of review Atrial fibrillation (AF) is the most common sustained arrhythmia in the patients with kidney disease. The purpose of this review is to describe the burden of AF in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), postulate possible mechanisms to explain this burden of disease, understand the clinical consequences of AF and review the treatment options for AF specific to patients with kidney disease. Recent findings Recent literature has revealed that the clinical multi-organ impact of AF in patients with CKD and ESRD is substantial. Although novel oral anticoagulants to treat AF and prevent associated complications have been tested in large trials in the general population, there is a paucity of data on the efficacy and safety of these agents in patients with advanced CKD and ESRD. Summary AF is a significant comorbidity in patients with CKD and ESRD with important prognostic implications. More research is needed to understand the mechanisms that contribute to the disproportionate burden of this arrhythmia in patients with kidney disease and treatment options specific to this population of high-risk patients. PMID:24709949

  17. Critical care of the hematopoietic stem cell transplant recipient.

    PubMed

    Afessa, Bekele; Azoulay, Elie

    2010-01-01

    An estimated 50,000 to 60,000 patients undergo hematopoietic stem cell transplantation (HSCT) worldwide annually, of which 15.7% are admitted to the intensive care unit (ICU). The most common reason for ICU admission is respiratory failure and almost all develop single or multiorgan failure. Most HSCT recipients admitted to ICU receive invasive mechanical ventilation (MV). The overall short-term mortality rate of HSCT recipients admitted to ICU is 65%, and 86.4% for those receiving MV. Patient outcome has improved over time. Poor prognostic indicators include advanced age, poor functional status, active disease at transplant, allogeneic transplant, the severity of acute illness, and the development of multiorgan failure. ICU resource limitations often lead to triage decisions for admission. For HSCT recipients, the authors recommend (1) ICU admission for full support during their pre-engraftment period and when there is no evidence of disease recurrence; (2) no ICU admission for patients who refuse it and those who are bedridden with disease recurrence and without treatment options except palliation; (3) a trial ICU admission for patients with unknown status of disease recurrence with available treatment options.

  18. Endoscopic therapy of neoplasia related to Barrett's esophagus and endoscopic palliation of esophageal cancer.

    PubMed

    Vignesh, Shivakumar; Hoffe, Sarah E; Meredith, Kenneth L; Shridhar, Ravi; Almhanna, Khaldoun; Gupta, Akshay K

    2013-04-01

    Barrett's esophagus (BE) is the most important identifiable risk factor for the progression to esophageal adenocarcinoma. This article reviews the current endoscopic therapies for BE with high-grade dysplasia and intramucosal cancer and briefly discusses the endoscopic palliation of advanced esophageal cancer. The diagnosis of low-grade or high-grade dysplasia (HGD) is based on several cytologic criteria that suggest neoplastic transformation of the columnar epithelium. HGD and carcinoma in situ are regarded as equivalent. The presence of dysplasia, particularly HGD, is also a risk factor for synchronous and metachronous adenocarcinoma. Dysplasia is a marker of adenocarcinoma and also has been shown to be the preinvasive lesion. Esophagectomy has been the conventional treatment for T1 esophageal cancer and, although debated, is an appropriate option in some patients with HGD due to the presence of occult cancer in over one-third of patients. Endoscopic ablative modalities (eg, photodynamic therapy and cryoablation) and endoscopic resection techniques (eg, endoscopic mucosal resection) have demonstrated promising results. The significant morbidity and mortality of esophagectomy makes endoscopic treatment an attractive potential option.

  19. The Meniscus-Deficient Knee

    PubMed Central

    Rao, Allison J.; Erickson, Brandon J.; Cvetanovich, Gregory L.; Yanke, Adam B.; Bach, Bernard R.; Cole, Brian J.

    2015-01-01

    Meniscal tears are the most common knee injury, and partial meniscectomies are the most common orthopaedic surgical procedure. The injured meniscus has an impaired ability to distribute load and resist tibial translation. Partial or complete loss of the meniscus promotes early development of chondromalacia and osteoarthritis. The primary goal of treatment for meniscus-deficient knees is to provide symptomatic relief, ideally to delay advanced joint space narrowing, and ultimately, joint replacement. Surgical treatments, including meniscal allograft transplantation (MAT), high tibial osteotomy (HTO), and distal femoral osteotomy (DFO), are options that attempt to decrease the loads on the articular cartilage of the meniscus-deficient compartment by replacing meniscal tissue or altering joint alignment. Clinical and biomechanical studies have reported promising outcomes for MAT, HTO, and DFO in the postmeniscectomized knee. These procedures can be performed alone or in conjunction with ligament reconstruction or chondral procedures (reparative, restorative, or reconstructive) to optimize stability and longevity of the knee. Complications can include fracture, nonunion, patella baja, compartment syndrome, infection, and deep venous thrombosis. MAT, HTO, and DFO are effective options for young patients suffering from pain and functional limitations secondary to meniscal deficiency. PMID:26779547

  20. The option value of innovative treatments in the context of chronic myeloid leukemia.

    PubMed

    Sanchez, Yuri; Penrod, John R; Qiu, Xiaoli Lily; Romley, John; Thornton Snider, Julia; Philipson, Tomas

    2012-11-01

    To quantify in the context of chronic myeloid leukemia (CML) the additional value patients receive when innovative treatments enable them to survive until the advent of even more effective future treatments (ie, the "option value"). Observational study using data from the Surveillance, Epidemiology and End Results (SEER) cancer registry comprising all US patients with CML diagnosed between 2000 and 2008 (N = 9,760). We quantified the option value of recent breakthroughs in CML treatment by first conducting retrospective survival analyses on SEER data to assess the effectiveness of TKI treatments, and then forecasting survival from CML and other causes to measure expected future medical progress. We then developed an analytical framework to calculate option value of innovative CML therapies, and used an economic model to value these gains. We calculated the option value created both by future innovations in CML treatment and by medical progress in reducing background mortality. For a recently diagnosed CML patient, the option value of innovative therapies from future medical innovation amounts to 0.76 life-years. This option value is worth $63,000, equivalent to 9% of the average survival gains from existing treatments. Future innovations in CML treatment jointly account for 96% of this benefit. The option value of innovative treatments has significance in the context of CML and, more broadly, in disease areas with rapid innovation. Incorporating option value into traditional valuations of medical innovations is both a feasible and a necessary practice in health technology assessment.

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