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Sample records for advanced pd patients

  1. Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer

    PubMed Central

    Brahmer, Julie R.; Tykodi, Scott S.; Chow, Laura Q.M.; Hwu, Wen-Jen; Topalian, Suzanne L.; Hwu, Patrick; Drake, Charles G.; Camacho, Luis H.; Kauh, John; Odunsi, Kunle; Pitot, Henry C.; Hamid, Omid; Bhatia, Shailender; Martins, Renato; Eaton, Keith; Chen, Shuming; Salay, Theresa M.; Alaparthy, Suresh; Grosso, Joseph F.; Korman, Alan J.; Parker, Susan M.; Agrawal, Shruti; Goldberg, Stacie M.; Pardoll, Drew M.; Gupta, Ashok; Wigginton, Jon M.

    2013-01-01

    BACKGROUND Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host’s immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. METHODS In this multicenter phase 1 trial, we administered intravenous anti–PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti–PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. RESULTS As of February 24, 2012, a total of 207 patients — 75 with non–small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer — had received anti–PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non–small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up. CONCLUSIONS Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non–small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.) PMID:22658128

  2. Correlation of Quantitative Motor State Assessment Using a Kinetograph and Patient Diaries in Advanced PD: Data from an Observational Study

    PubMed Central

    Ossig, Christiana; Gandor, Florin; Fauser, Mareike; Bosredon, Cecile; Churilov, Leonid; Reichmann, Heinz; Horne, Malcolm K.; Ebersbach, Georg; Storch, Alexander

    2016-01-01

    Introduction Effective management and development of new treatment strategies for response fluctuations in advanced Parkinson’s disease (PD) largely depends on clinical rating instruments such as the PD home diary. The Parkinson’s kinetigraph (PKG) measures movement accelerations and analyzes the spectral power of the low frequencies of the accelerometer data. New algorithms convert each hour of continuous PKG data into one of the three motor categories used in the PD home diary, namely motor Off state and On state with and without dyskinesia. Objective To compare quantitative motor state assessment in fluctuating PD patients using the PKG with motor state ratings from PD home diaries. Methods Observational cohort study on 24 in-patients with documented motor fluctuations who completed diaries by rating motor Off, On without dyskinesia, On with dyskinesia, and asleep for every hour for 5 consecutive days. Simultaneously collected PKG data (recorded between 6 am and 10 pm) were analyzed and calibrated to the patient’s individual thresholds for Off and dyskinetic state by novel algorithms classifying the continuous accelerometer data into these motor states for every hour between 6 am and 10 pm. Results From a total of 2,040 hours, 1,752 hours (87.4%) were available for analyses from calibrated PKG data (7.5% sleeping time and 5.1% unclassified motor state time were excluded from analyses). Distributions of total motor state hours per day measured by PKG showed moderate-to-strong correlation to those assessed by diaries for the different motor states (Pearson’s correlations coefficients: 0.404–0.658), but inter-rating method agreements on the single-hour-level were only low-to-moderate (Cohen’s κ: 0.215–0.324). Conclusion The PKG has been shown to capture motor fluctuations in patients with advanced PD. The limited correlation of hour-to-hour diary and PKG recordings should be addressed in further studies. PMID:27556806

  3. Anti-PD-1/PD-L1 antibody therapy for pretreated advanced nonsmall-cell lung cancer

    PubMed Central

    Zhou, Guo-Wu; Xiong, Ye; Chen, Si; Xia, Fan; Li, Qiang; Hu, Jia

    2016-01-01

    Abstract Background: Anti-PD-1/PD-L1 antibody therapy is a promising clinical treatment for nonsmall-cell lung cancer (NSCLC). However, whether anti-PD-1/PD-L1 antibody therapy can provide added benefits for heavily pretreated patients with advanced NSCLC and whether the efficacy of anti-PD-1/PD-L1 antibody therapy relates to the tumor PD-L1 expression level remain controversial. Thus, this meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 antibody therapy for pretreated patients with advanced NSCLC. Methods: Randomized clinical trials were retrieved by searching the PubMed, EMBASE, ASCO meeting abstract, clinicaltrial.gov, and Cochrane library databases. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios for the overall response rate and adverse events (AEs) were calculated by STATA software. Results: Three randomized clinical trials involving 1141 pretreated patients with advanced NSCLC were included. These trials all compared the efficacy and safety of anti-PD-1/PD-L1 antibodies (nivolumab and MPDL3280A) with docetaxel. The results suggested that, for all patients, anti-PD-1/PD-L1 therapy could acquire a greater overall response (odds ratio = 1.50, 95% CI: 1.08–2.07, P = 0.015, P for heterogeneity [Ph] = 0.620) and longer OS (HR = 0.71, 95% CI: 0.61–0.81, P < 0.001, Ph = 0.361) than docetaxel, but not PFS (HR = 0.83, 95% CI: 0.65–1.06, P = 0.134; Ph = 0.031). Subgroup analyses according to the tumor PD-L1 expression level showed that anti-PD-1/PD-L1 therapy could significantly improve both OS and PFS in patients with high expressions of PD-L1, but not in those with low expressions. Generally, the rates of grade 3 or 4 AEs of anti-PD-1/PD-L1 therapy were significantly lower than that of docetaxel. However, the risks of pneumonitis and hypothyroidism were significantly higher. Conclusion: Anti-PD-1/PD-L1 antibody therapy may significantly improve

  4. Rotigotine transdermal system for long-term treatment of patients with advanced Parkinson's disease: results of two open-label extension studies, CLEOPATRA-PD and PREFER.

    PubMed

    LeWitt, Peter A; Boroojerdi, Babak; Surmann, Erwin; Poewe, Werner

    2013-07-01

    Open-label extensions [studies SP516 (NCT00501969) and SP715 (NCT00594386)] of the CLEOPATRA-PD and PREFER studies were conducted to evaluate the safety, tolerability and efficacy of the dopaminergic agonist, rotigotine, over several years of follow-up in patients with advanced Parkinson's disease (PD). Eligible subjects completing the double-blind trials received open-label adjunctive rotigotine (≤16 mg/24 h) for up to 4 and 6 years in Studies SP516 and SP715, respectively. Safety and tolerability were assessed using adverse events, vital signs and laboratory parameters, and efficacy assessed using the unified Parkinson's disease rating scale (UPDRS). Of the 395 and 258 patients enrolled in the SP516 and SP715 studies, 48 and 45 % completed, respectively. Adverse events were typically dopaminergic effects [e.g., somnolence (18-25 %/patient-year), insomnia (5-7 %/patient-year), dyskinesias (4-8 %/patient-year) and hallucinations (4-8 %/patient-year)], or related to the transdermal application of a patch (application site reactions: 14-15 %/patient-year). There were no clinically relevant changes in vital signs or laboratory parameters in either study. Mean UPDRS part II (activities of daily living) and part III (motor function) total scores improved from double-blind baseline during dose titration, then gradually declined over the maintenance period. In study SP516, mean UPDRS part II and III total scores were 0.8 points above and 2.8 points below double-blind baseline, respectively, at end of treatment. In study SP715, mean UPDRS part II and III total scores were 4.1 points above and 0.2 points below baseline, respectively, at end of treatment. In these open-label studies, adjunctive rotigotine was efficacious with an acceptable safety and tolerability profile in patients with advanced PD for up to 6 years.

  5. [Perioperative Management of PD Patients].

    PubMed

    Reichmann, H

    2016-07-01

    Both patients and caregivers but also treating physicians are concerned about complications along with surgical interventions. A major problem is abrupt cessation of anti-Parkinson medication, which leads to manifold disturbances, sometimes even to an akinetic crisis. There are several means to guarantee continuous dopaminergic stimulation even in patients that are not allowed to take medication orally before they undergo surgery. Amongst others rectally applied levodopa, amantadine infusions, and especially the use of a rotigotine patch are good means to overcome oral intake. Perioperative management is important due to the fact that in Germany alone each year more than 10 000 PD patients undergo surgery. Main reasons for this are fractures, but also elective interventions. Further emergency situations that cause treatment as an inpatient are psychosis, motoric disability, but also pneumonia and cardiovascular disturbances. In contrast PD patients suffer less often from cancer. PMID:27276074

  6. Phase 1 study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced solid tumors.

    PubMed

    Shimizu, Toshio; Seto, Takashi; Hirai, Fumihiko; Takenoyama, Mitsuhiro; Nosaki, Kaname; Tsurutani, Junji; Kaneda, Hiroyasu; Iwasa, Tsutomu; Kawakami, Hisato; Noguchi, Kazuo; Shimamoto, Takashi; Nakagawa, Kazuhiko

    2016-06-01

    Background This phase I study evaluated the safety and tolerability, pharmacokinetics and pharmacodynamics, immunogenicity, and antitumor activity of pembrolizumab in Japanese patients with advanced solid tumors. Methods Following an initial dose and a 28-day rest (cycle 1), pembrolizumab was administered as an intravenous infusion at escalating doses (2 or 10 mg/kg) every 2 weeks (Q2W) until disease progression or unacceptable toxicity. Adverse events (AEs) were assessed using CTCAE v4.0, and tumor response was assessed using both RECIST v1.1 and immune-related response criteria (irRC). Full pharmacokinetic sampling was performed during cycle 1. Results Three patients received pembrolizumab at 2.0 mg/kg and seven at 10 mg/kg. No dose-limiting toxicities were observed during cycle 1. Eighty percent of patients experienced drug-related AEs (mostly grade 1 or 2); the most common drug-related AEs were nausea, malaise, pyrexia, and aspartate aminotransferase/alanine transaminase (AST/ALT) elevations (n = 2 each). No drug-related grade 4 or 5 AEs occurred. Immune-related AEs comprised grade 3 ALT elevation (n = 1), grade 3 AST elevation (n = 1), grade 1 pneumonitis (n = 1), and grade 1 thyroid-stimulating hormone elevation (n = 1). The safety and pharmacokinetic profiles of Japanese patients were similar to those previously reported for Caucasian patients. A partial tumor response was observed in one patient with non-small-cell lung cancer (NSCLC) and in one patient with melanoma. Conclusions Pembrolizumab at both 2 and 10 mg/kg Q2W was well tolerated in Japanese patients with advanced solid tumors and showed encouraging anti-tumor activity against melanoma and NSCLC.

  7. The clinical utility of PD-L1 testing in selecting non-small cell lung cancer patients for PD1/PD-L1-directed therapy.

    PubMed

    Villaruz, L C; Socinski, M A

    2016-09-01

    Lung cancer is the leading cause of cancer mortality in the United States and worldwide. Long thought to be nonimmunogenic, immunotherapy in lung cancer has historically been met with disappointing results. Programmed death-1 (PD-1), and the PD-1 ligand, PD-L1, are immune checkpoint proteins that fine-tune the antigen-specific T-cell response after stimulation of the T-cell receptor and are crucial for self-tolerance. This pathway in particular is co-opted by tumors through expression of PD-L1 on the tumor cell surface and within the tumor microenvironment, allowing for direct suppression of antitumor cytolytic T-cell activity by the tumor. Indeed, induction of the PD1/PD-L1 pathway represents an adaptive immune resistance mechanism exerted by tumor cells in response to endogenous antitumor activity. In 2015, the US Food and Drug Administration (FDA) approved two immuno-oncology agents, the PD-1 inhibitors nivolumab and pembrolizumab, for the treatment of previously treated advanced non-small cell lung cancer (NSCLC). Coincident with the clinical trials that led to these regulatory approvals has been the development of several immunohistochemistry (IHC) tests of PD-L1 expression, which may serve to select patients who will derive the most benefit from PD1- or PD-L1-directed therapy. The PD-L1 IHC assays are distinct in their methods and interpretation, which poses a challenge to clinicians selecting patients for these therapies.

  8. TIGIT and PD-1 impair tumor antigen–specific CD8+ T cells in melanoma patients

    PubMed Central

    Chauvin, Joe-Marc; Pagliano, Ornella; Fourcade, Julien; Sun, Zhaojun; Wang, Hong; Sander, Cindy; Kirkwood, John M.; Chen, Tseng-hui Timothy; Maurer, Mark; Korman, Alan J.; Zarour, Hassane M.

    2015-01-01

    T cell Ig and ITIM domain (TIGIT) is an inhibitory receptor expressed by activated T cells, Tregs, and NK cells. Here, we determined that TIGIT is upregulated on tumor antigen–specific (TA-specific) CD8+ T cells and CD8+ tumor-infiltrating lymphocytes (TILs) from patients with melanoma, and these TIGIT-expressing CD8+ T cells often coexpress the inhibitory receptor PD-1. Moreover, CD8+ TILs from patients exhibited downregulation of the costimulatory molecule CD226, which competes with TIGIT for the same ligand, supporting a TIGIT/CD226 imbalance in metastatic melanoma. TIGIT marked early T cell activation and was further upregulated by T cells upon PD-1 blockade and in dysfunctional PD-1+TIM-3+ TA-specific CD8+ T cells. PD-1+TIGIT+, PD-1–TIGIT+, and PD-1+TIGIT– CD8+ TILs had similar functional capacities ex vivo, suggesting that TIGIT alone, or together with PD-1, is not indicative of T cell dysfunction. However, in the presence of TIGIT ligand–expressing cells, TIGIT and PD-1 blockade additively increased proliferation, cytokine production, and degranulation of both TA-specific CD8+ T cells and CD8+ TILs. Collectively, our results show that TIGIT and PD-1 regulate the expansion and function of TA-specific CD8+ T cells and CD8+ TILs in melanoma patients and suggest that dual TIGIT and PD-1 blockade should be further explored to elicit potent antitumor CD8+ T cell responses in patients with advanced melanoma. PMID:25866972

  9. Subjective Visual Vertical in PD Patients with Lateral Trunk Flexion

    PubMed Central

    Gandor, F.; Basta, D.; Gruber, D.; Poewe, W.; Ebersbach, G.

    2016-01-01

    Lateral trunk flexion (LTF) is a common phenomenon in patients with Parkinson's disease (PD) and has recently been associated with peripheral vestibular dysfunction. Since deviation of the subjective visual vertical (SVV) is a well-recognized feature of disorders involving vestibular processing, we analyzed SVV angles in 30 PD patients with and without LTF to assess the possible role of vestibular dysfunction in the pathogenesis of LTF in PD. Quantification of SVV was obtained using a simple bedside test. PD patients with LTF had significantly greater SVV angles as compared to PD patients without LTF (median: 4.3° [range: 0.1–17.7], n = 21, versus 0.8° [0.1–1.9], n = 9; p < 0.001). 14 of 21 patients with LTF showed pathological SVV, while all 9 patients without LTF had normal SVV. Abnormal SVV was more frequent when LTF was reversible in the supine position compared to fixed LTF. In a subgroup of PD patients with LTF, pathological SVV suggests vestibular dysbalance, which might be involved in the pathophysiological mechanisms underlying LTF. PMID:27073710

  10. PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma

    PubMed Central

    Nghiem, Paul T.; Bhatia, Shailender; Lipson, Evan J.; Kudchadkar, Ragini R.; Miller, Natalie J.; Annamalai, Lakshmanan; Berry, Sneha; Chartash, Elliot K.; Daud, Adil; Fling, Steven P.; Friedlander, Philip A.; Kluger, Harriet M.; Kohrt, Holbrook E.; Lundgren, Lisa; Margolin, Kim; Mitchell, Alan; Olencki, Thomas; Pardoll, Drew M.; Reddy, Sunil A.; Shantha, Erica M.; Sharfman, William H.; Sharon, Elad; Shemanski, Lynn R.; Shinohara, Michi M.; Sunshine, Joel C.; Taube, Janis M.; Thompson, John A.; Townson, Steven M.; Yearley, Jennifer H.; Topalian, Suzanne L.; Cheever, Martin A.

    2016-01-01

    BACKGROUND Merkel-cell carcinoma is an aggressive skin cancer that is linked to exposure to ultraviolet light and the Merkel-cell polyomavirus (MCPyV). Advanced Merkel-cell carcinoma often responds to chemotherapy, but responses are transient. Blocking the programmed death 1 (PD-1) immune inhibitory pathway is of interest, because these tumors often express PD-L1, and MCPyV-specific T cells express PD-1. METHODS In this multicenter, phase 2, noncontrolled study, we assigned adults with advanced Merkel-cell carcinoma who had received no previous systemic therapy to receive pembrolizumab (anti–PD-1) at a dose of 2 mg per kilogram of body weight every 3 weeks. The primary end point was the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1. Efficacy was correlated with tumor viral status, as assessed by serologic and immunohistochemical testing. RESULTS A total of 26 patients received at least one dose of pembrolizumab. The objective response rate among the 25 patients with at least one evaluation during treatment was 56% (95% confidence interval [CI], 35 to 76); 4 patients had a complete response, and 10 had a partial response. With a median follow-up of 33 weeks (range, 7 to 53), relapses occurred in 2 of the 14 patients who had had a response (14%). The response duration ranged from at least 2.2 months to at least 9.7 months. The rate of progression-free survival at 6 months was 67% (95% CI, 49 to 86). A total of 17 of the 26 patients (65%) had virus-positive tumors. The response rate was 62% among patients with MCPyV-positive tumors (10 of 16 patients) and 44% among those with virus-negative tumors (4 of 9 patients). Drug-related grade 3 or 4 adverse events occurred in 15% of the patients. CONCLUSIONS In this study, first-line therapy with pembrolizumab in patients with advanced Merkel-cell carcinoma was associated with an objective response rate of 56%. Responses were observed in patients with virus-positive tumors

  11. Tissue-Advanced Glycation End Product Concentration in Dialysis Patients

    PubMed Central

    McIntyre, Natasha J.; Chesterton, Lindsay J.; John, Stephen G.; Jefferies, Helen J.; Burton, James O.; Taal, Maarten W.; Fluck, Richard J.

    2010-01-01

    Background and objectives: Tissue-advanced glycation end products (AGE) are a measure of cumulative metabolic stress. Assessment of tissue AGE by skin autofluoresence (AF) correlates well with cardiovascular outcomes in hemodialysis (HD) patients. This study aimed to measure and compare tissue AGE levels in HD and peritoneal dialysis (PD) patients and to evaluate the impact of systemic PD glucose exposure. Design, setting, participants, & measurements: Tissue AGE were measured in 115 established dialysis patients (62 HD and 53 PD) using a cutaneous AF device (AGE Reader; DiagnOptics). Values were compared with an age-matched non–chronic kidney disease database. Review of all previous PD solution delivery/prescription data determined PD glucose exposure. Results: PD patients were similar in age to HD patients but had a shorter dialysis vintage. There were no differences in ischemic heart disease or smoking history, statin or angiotensin-converting enzyme inhibitor (ACEi) use, lipids, biochemistry, or prevalence of diabetes. More than 90% of both groups had met current dialysis adequacy targets. Skin AF values in PD and HD patients were similar and strongly correlated with historical PD glucose exposure. Skin AF correlated with age in both groups but with dialysis vintage only in PD patients Conclusions: Cumulative metabolic stress and transient hyperglycemia results in grossly elevated levels of tissue AGE in dialysis patients. In PD patients, this high level of AGE deposition is associated with historical glucose exposure. This observation provides a previously unappreciated potential link between PD exposure to glucose and systemic cardiovascular disease. PMID:19965551

  12. Cancer Treatment with Anti-PD-1/PD-L1 Agents: Is PD-L1 Expression a Biomarker for Patient Selection?

    PubMed

    Festino, Lucia; Botti, Gerardo; Lorigan, Paul; Masucci, Giuseppe V; Hipp, Jason D; Horak, Christine E; Melero, Ignacio; Ascierto, Paolo A

    2016-06-01

    Strategies to help improve the efficacy of the immune system against cancer represent an important innovation, with recent attention having focused on anti-programmed death (PD)-1/PD-ligand 1 (L1) monoclonal antibodies. Clinical trials have shown objective clinical activity of these agents (e.g., nivolumab, pembrolizumab) in several malignancies, including melanoma, non-small-cell lung cancer, bladder cancer, squamous head and neck cancer, renal cell cancer, ovarian cancer, microsatellite-unstable colorectal cancer, and Hodgkin's lymphoma. Expression of PD-L1 in the tumor microenvironment appears to be crucial for therapeutic activity, and initial trials suggested positive PD-L1 tumor expression was associated with higher response rates. However, subsequent observations have questioned the prospect of using PD-L1 expression as a biomarker for selecting patients for therapy, especially since many patients considered PD-L1-negative experience a benefit from treatment. Importantly, there is not yet a definitive test for determination of PD-L1 and a cut-off reference for PD-L1-positive status has not been established. Immunohistochemistry with different antibodies and different thresholds has been used to define PD-L1 positivity (1-50 %), with no clear superiority of one threshold over another for identifying which patients respond. Moreover, the type of cells on which PD-L1 expression is most relevant is not yet clear, with immune infiltrate cells and tumor cells both being used. In conclusion, while PD-L1 expression is often a predictive factor for treatment response, it must be complemented by other biomarkers or histopathologic features, such as the composition and amount of inflammatory cells in the tumor microenvironment and their functional status. Multi-parameter quantitative or semi-quantitative algorithms may become useful and reliable tools to guide patient selection. PMID:27229745

  13. The anticancer immune response of anti-PD-1/PD-L1 and the genetic determinants of response to anti-PD-1/PD-L1 antibodies in cancer patients.

    PubMed

    Sui, Xinbing; Ma, Junhong; Han, Weidong; Wang, Xian; Fang, Yong; Li, Da; Pan, Hongming; Zhang, Li

    2015-08-14

    The programmed death-1 (PD-1), a coinhibitory receptor expressed on activated T cells and B cells, is demonstrated to induce an immune-mediated response and play a critical role in tumor initiation and development. The cancer patients harboring PD-1 or PD ligand 1 (PD-L1) protein expression have often a poor prognosis and clinical outcome. Currently, targeting PD-1 pathway as a potential new anticancer strategy is attracting more and more attention in cancer treatment. Several monoclonal antibodies against PD-1 or PD-L1 have been reported to enhance anticancer immune responses and induce tumor cell death. Nonetheless, the precise molecular mechanisms by which PD-1 affects various cancers remain elusive. Moreover, this therapy is not effective for all the cancer patients and only a fraction of patients respond to the antibodies targeting PD-1 or PD-L1, indicating these antibodies may only works in a subset of certain cancers. Thus, understanding the novel function of PD-1 and genetic determinants of response to anti-PD-1 therapy will allow us to develop a more effective and individualized immunotherapeutic strategy for cancer.

  14. Antitumor vaccination of prostate cancer patients elicits PD-1/PD-L1 regulated antigen-specific immune responses.

    PubMed

    Rekoske, Brian T; Olson, Brian M; McNeel, Douglas G

    2016-06-01

    We have previously reported that tumor antigen-specific DNA vaccination in mice led to an increase in IFNγ-secreting T cells and an increase in tumor expression of PD-L1. Further, we demonstrated that increasing the encoded antigen's MHC-binding affinity led to increased PD-1 expression on antigen-specific CD8(+) T cells. Together these phenomena provided resistance to antitumor immunization that was abrogated with PD-1/PD-L1 blockade. We consequently sought to determine whether similar regulation occurred in human patients following antitumor immunization. Using clinical samples from prostate cancer patients who were previously immunized with a DNA vaccine, we analyzed changes in checkpoint receptor expression on antigen-specific CD8(+) T cells, the effect of PD-1 blockade on elicited immune responses, and for changes in checkpoint ligand expression on patients' circulating tumor cells (CTCs). We observed no significant changes in T-cell expression of PD-1 or other checkpoint receptors, but antigen-specific immune responses were detected and/or augmented with PD-1 blockade as detected by IFNγ and granzyme B secretion or trans vivo DTH testing. Moreover, PD-L1 expression was increased on CTCs following vaccination, and this PD-L1 upregulation was associated with the development of sustained T-cell immunity and longer progression-free survival. Finally, similar results were observed with patients treated with sipuleucel-T, another vaccine targeting the same prostate antigen. These findings provide in-human rationale for combining anticancer vaccines with PD-1 blocking antibodies, particularly for the treatment of prostate cancer, a disease for which vaccines have demonstrated benefit and yet PD-1 inhibitors have shown little clinical benefit to date as monotherapies. PMID:27471641

  15. Functional capacity of Brazilian patients with Parkinson's disease (PD): relationship between clinical characteristics and disease severity.

    PubMed

    Barbieri, Fabio A; Rinaldi, Natalia M; Santos, Paulo Cezar R; Lirani-Silva, Ellen; Vitório, Rodrigo; Teixeira-Arroyo, Cláudia; Stella, Florindo; Gobbi, Lilian Teresa B

    2012-01-01

    The present study had three objectives: (a) to characterize the functional capacity of patients with PD, (b) to assess the relationship between the physical fitness components of functional capacity with clinical characteristics and disease severity, and (c) to compare the physical fitness components of functional capacity with clinical characteristics according to disease severity. The study included 54 patients with idiopathic PD who were distributed into two groups according to PD severity: unilateral group (n=35); and bilateral group (n=19). All patients underwent psychiatric assessment by means of the Hoehn and Yahr (HY) staging of PD, the Unified Parkinson's Disease Rating Scale (UPDRS), the Hospital Anxiety and Depression Scale (HADS-A and HADS-D, respectively), and The Mini-Mental State Examination (MMSE). The physical fitness components of functional capacity were evaluated over a 2-day period, using recommendations by the American Alliance for Health, Physical Education, Recreation and Dance, and the Berg Balance Scale (BBS). Pearson correlation coefficients and multiple regressions were calculated to test the correlation between functional capacity and clinical characteristics, and to predict clinical scores from physical performance, respectively. Clinical variables and physical component data were compared between groups using analysis of variance to determine the effects of disease severity. Patients with advanced disease showed low levels of functional capacity. Interestingly, patients with good functional capacity in one of the physical fitness components also showed good capacities in the other components. Disease severity is a major factor affecting functional capacity and clinical characteristics. Medical providers should take disease severity into consideration when prescribing physical activity for PD patients, since the relationship between functional capacity and clinical characteristics is dependent on disease severity. PMID:21963176

  16. PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysis

    PubMed Central

    Natoli, Clara; Rizzo, Sergio; Galvano, Antonio; Listì, Angela; Cicero, Giuseppe; Rolfo, Christian; Santini, Daniele; Russo, Antonio

    2016-01-01

    Background Clinical trials of immune checkpoints modulators, including both programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors, have recently shown promising activity and tolerable toxicity in pre-treated NSCLC patients. However the predictive role of PD-L1 expression is still controversial. This pooled analysis aims to clarify the association of clinical objective responses to anti PD-1/PD-L1 monoclonal antibodies (MoAbs) and tumor PD-L1 expression in pre-treated NSCLC patients. Methods Data from published studies, that evaluated efficacy and safety of PD-1/PD-L1 inhibitors in pre-treated NSCLC patients, stratified by tumor PD-L1 expression status (immunohistochemistry, cut-off point 1%), were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference of Lung Cancer, meeting proceedings. Pooled Odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated for the Overall Response Rate (ORR) (as evaluated by Response Evaluation Criteria in Solid Tumors, version 1.1), according to PD-L1 expression status. Results A total of seven studies, with 914 patients, were eligible. Pooled analysis showed that patients with PD-L1 positive tumors (PD-L1 tumor cell staining ≥1%), had a significantly higher ORR, compared to patients with PD-L1 negative tumors (OR: 2.44; 95% CIs: 1.61-3.68). Conclusions PD-L1 tumor over-expression seems to be associated with higher clinical activity of anti PD-1/PD-L1 MoAbs, in pre-treated NSCLC patients, suggesting a potential role of PD-L1 expression, IHC cut-off point 1%, as predictive biomarker for the selection of patients to treat with immune-checkpoint inhibitors. PMID:26918451

  17. Soluble Programmed Death 1 (PD-1) Is Decreased in Patients With Immune Thrombocytopenia (ITP): Potential Involvement of PD-1 Pathway in ITP Immunopathogenesis.

    PubMed

    Birtas Atesoglu, Elif; Tarkun, Pinar; Demirsoy, Esra Terzi; Geduk, Ayfer; Mehtap, Ozgur; Batman, Adnan; Kaya, Fatih; Cekmen, Mustafa Baki; Gulbas, Zafer; Hacıhanefioglu, Abdullah

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune disease characterized by dysregulation of T cells. Programmed death (PD) 1 and programmed death 1 ligand 1 (PD-L1) are cosignaling molecules, and the major role of the PD-1 pathway is the inhibition of self-reactive T cells and to protect against autoimmune diseases. We measured levels of serum soluble PD 1 (sPD-1) and serum soluble PD-L1 (sPD-L1) in 67 patients with ITP (24 newly diagnosed ITP [ndITP], 43 chronic ITP [cITP]) and 21 healthy controls (HCs). We determined decreased serum sPD-1 levels both in patients with ndITP and in patients with cITP when compared to HC. Moreover, there was a positive correlation between sPD-1 levels and platelet counts. The sPD-L1 levels were decreased in patients with ndITP when compared to patients with cITP. This is the first study investigating PD-1 signaling pathway in ITP. Decreased sPD-1 levels may have a role in ITP pathogenesis as without the inhibitory regulation of PD-1, sustained activation of T cells may cause inflammatory responses which is the case in ITP.

  18. PD-L1 is an independent prognostic predictor in gastric cancer of Western patients

    PubMed Central

    Böger, Christine; Behrens, Hans-Michael; Mathiak, Micaela; Krüger, Sandra; Kalthoff, Holger; Röcken, Christoph

    2016-01-01

    Targeting the PD-1/PD-L1 immune checkpoint signaling is a novel promising treatment strategy in several tumor entities, and it is suggested that PD-L1/PD-1 expression is predictive for a PD-1/PD-L1 checkpoint inhibitor treatment response. We investigated the expression of PD-L1 and PD-1 by immunohistochemistry in a large and well characterized gastric cancer (GC) cohort of Caucasian patients, consisting of 465 GC samples and 15 corresponding liver metastases. Staining results were correlated with clinico-pathological characteristics and survival. PD-L1 expression was found in tumor cells of 140 GCs (30.1%) and 9 liver metastases (60%) respectively in immune cells of 411 GCs (88.4%) and 11 liver metastases (73.3%). PD-1 was expressed in tumor infiltrating lymphocytes in 250 GCs (53.8%) and in 11 liver metastases (73.3%). PD-L1 expression was significantly more prevalent in men, GCs of the proximal stomach, unclassified, papillary, Her2/neu-positive, Epstein-Barr-virus-positive, microsatellite instable, and PIK3CA-mutated GCs. A high PD-L1/PD-1 expression was associated with a significantly better patient outcome, and PD-L1 turned out to be an independent survival prognosticator. The correlation of PD-L1/PD-1 expression with distinct clinico-pathological patient characteristics may serve as a surrogate marker of PD-L1-positive GCs and may direct the use of immune checkpoint treatment strategies. PMID:27009855

  19. PD-1+ and Foxp3+ T cell reduction correlates with survival of HCC patients after sorafenib therapy

    PubMed Central

    Kalathil, Suresh Gopi; Lugade, Amit Anand; Iyer, Renuka

    2016-01-01

    BACKGROUND. Sorafenib is an oral antiangiogenic agent administered in advanced-stage hepatocellular carcinoma (HCC). Based on preclinical and human studies, we hypothesized that, in addition to its antiangiogenic properties, sorafenib may beneficially reduce the extent of the immunosuppressive network in HCC patients. To test this hypothesis, we examined whether alterations in the immunosuppressive burden of advanced-stage HCC patients correlated with clinical outcome. METHODS. In before and after sorafenib treatment, blood samples collected from 19 patients with advanced HCC, the frequency of PD-1+ T cells, Tregs, and myeloid derived suppressor cells (MDSC) were quantified by multiparameter FACS. Cytokine levels in plasma were determined by ELISA. RESULTS. Overall survival (OS) was significantly impacted by the reduction in the absolute number of both CD4+PD-1+ T cells and CD8+PD-1+ T cells following sorafenib treatment. Significant decreases in the frequency and absolute number of Foxp3+ Tregs were also observed, and a statistically significant improvement in OS was noted in patients exhibiting a greater decrease in the number of Foxp3+ Tregs. The ratio of CD4+CD127+PD-1– T effector cells to CD4+Foxp3+PD-1+ Tregs was significantly increased following treatment with sorafenib. Increased frequency of CD4+CD127+ T effector cells in the posttreatment samples significantly correlated with OS. CONCLUSION. This study is the first to our knowledge to demonstrate the potent immunomodulatory effects of sorafenib therapy on PD-1+ T cells and Tregs and the ensuing correlation with survival. These phenotypes could serve as predictive biomarkers to identify HCC patients who are likely to benefit from sorafenib treatment. TRIAL REGISTRATION. Registration is not required for observational studies. FUNDING. This study was supported by NCI Core Grant to RPCI (NIH P30 CA016056) and discretionary funds to Y. Thanavala. PMID:27540594

  20. PD-1+ and Foxp3+ T cell reduction correlates with survival of HCC patients after sorafenib therapy

    PubMed Central

    Kalathil, Suresh Gopi; Lugade, Amit Anand; Miller, Austin; Iyer, Renuka; Thanavala, Yasmin

    2016-01-01

    BACKGROUND Sorafenib is an oral antiangiogenic agent administered in advanced-stage hepatocellular carcinoma (HCC). Based on preclinical and human studies, we hypothesized that, in addition to its antiangiogenic properties, sorafenib may beneficially reduce the extent of the immunosuppressive network in HCC patients. To test this hypothesis, we examined whether alterations in the immunosuppressive burden of advanced-stage HCC patients correlated with clinical outcome. METHODS In before and after sorafenib treatment, blood samples collected from 19 patients with advanced HCC, the frequency of PD-1+ T cells, Tregs, and myeloid derived suppressor cells (MDSC) were quantified by multiparameter FACS. Cytokine levels in plasma were determined by ELISA. RESULTS Overall survival (OS) was significantly impacted by the reduction in the absolute number of both CD4+PD-1+ T cells and CD8+PD-1+ T cells following sorafenib treatment. Significant decreases in the frequency and absolute number of Foxp3+ Tregs were also observed, and a statistically significant improvement in OS was noted in patients exhibiting a greater decrease in the number of Foxp3+ Tregs. The ratio of CD4+CD127+PD-1− T effector cells to CD4+Foxp3+PD-1+ Tregs was significantly increased following treatment with sorafenib. Increased frequency of CD4+CD127+ T effector cells in the posttreatment samples significantly correlated with OS. CONCLUSION This study is the first to our knowledge to demonstrate the potent immunomodulatory effects of sorafenib therapy on PD-1+ T cells and Tregs and the ensuing correlation with survival. These phenotypes could serve as predictive biomarkers to identify HCC patients who are likely to benefit from sorafenib treatment. TRIAL REGISTRATION Registration is not required for observational studies. FUNDING This study was supported by NCI Core Grant to RPCI (NIH P30 CA016056) and discretionary funds to Y. Thanavala. PMID:27540594

  1. Monitoring PD-L1 positive circulating tumor cells in non-small cell lung cancer patients treated with the PD-1 inhibitor Nivolumab

    PubMed Central

    Nicolazzo, Chiara; Raimondi, Cristina; Mancini, MariaLaura; Caponnetto, Salvatore; Gradilone, Angela; Gandini, Orietta; Mastromartino, Maria; del Bene, Gabriella; Prete, Alessandra; Longo, Flavia; Cortesi, Enrico; Gazzaniga, Paola

    2016-01-01

    Controversial results on the predictive value of programmed death ligand 1 (PD-L1) status in lung tumor tissue for response to immune checkpoint inhibitors do not allow for any conclusive consideration. Liquid biopsy might allow real-time sampling of patients for PD-L1 through the course of the disease. Twenty-four stage IV NSCLC patients included in the Expanded Access Program with Nivolumab were enrolled. Circulating tumor cells (CTCs) were analyzed by CellSearch with anti-human B7-H1/PD-L1 PE-conjugated antibody. PD-L1 expressing CTCs were assessed at baseline, at 3 and 6 months after starting therapy, and correlated with outcome. At baseline and at 3 months of treatment, the presence of CTCs and the expression of PD-L1 on their surface were found associated to poor patients outcome. Nevertheless, the high frequency of PD-L1 expressing CTCs hampered to discriminate the role of PD-L1 in defining prognosis. Conversely although CTCs were found in all patients 6 months after treatment, at this time patients could be dichotomized into two groups based PD-L1 expression on CTCs. Patients with PD-L1 negative CTCs all obtained a clinical benefit, while patients with PD-L1 (+) CTCs all experienced progressive disease. This suggests that the persistence of PD-L1(+) CTCs might mirror a mechanism of therapy escape. PMID:27553175

  2. Fabrication of Pd/Pd-Alloy Films by Surfactant Induced Electroless Plating for Hydrogen Separation from Advanced Coal Gasification Processes

    SciTech Connect

    Ilias, Shamsuddin; Kumar, Dhananjay

    2012-07-31

    Dense Pd, Pd-Cu and Pd-Ag composite membranes on microporous stainless steel substrate (MPSS) were fabricated by a novel electroless plating (EP) process. In the conventional Pd-EP process, the oxidation-reduction reactions between Pd-complex and hydrazine result in an evolution of NH{sub 3} and N{sub 2} gas bubbles. When adhered to the substrate surface and in the pores, these gas bubbles hinder uniform Pd-film deposition which results in dendrite growth leading to poor film formation. This problem was addressed by introducing cationic surfactant in the electroless plating process known as surfactant induced electroless plating (SIEP). The unique features of this innovation provide control of Pd-deposition rate, and Pd-grain size distribution. The surfactant molecules play an important role in the EP process by tailoring grain size and the process of agglomeration by removing tiny gas bubbles through adsorption at the gas-liquid interface. As a result surfactant can tailor a nanocrystalline Pd, Cu and Ag deposition in the film resulting in reduced membrane film thickness. Also, it produces a uniform, agglomerated film structure. The Pd-Cu and Pd-Ag membranes on MPSS support were fabricated by sequential deposition using SIEP method. The pre- and post-annealing characterizations of these membranes (Pd, Pd-Cu and Pd-Ag on MPSS substrate) were carried out by SEM, EDX, XRD, and AFM studies. The SEM images show significant improvement of the membrane surface morphology, in terms of metal grain structures and grain agglomeration compared to the membranes fabricated by conventional EP process. The SEM images and helium gas-tightness studies indicate that dense and thinner films of Pd, Pd-Cu and Pd-Ag membranes can be produced with shorter deposition time using surfactant. H{sub 2} Flux through the membranes fabricated by SIEP shows large improvement compared to those by CEP with comparable permselectivity. Pd-MPSS composite membrane was subjected to test for long term

  3. Antagonist Antibodies to PD-1 and B7-H1 (PD-L1) in the Treatment of Advanced Human Cancer

    PubMed Central

    Sznol, Mario; Chen, Lieping

    2013-01-01

    The immune suppressive molecule PD-1 is up-regulated in activated T lymphocytes and inhibits T-cell function upon binding to its ligands B7-H1 (PD-L1, CD274) and B7-DC (PD-L2, CD273). Substantial experimental data from in vitro cell culture systems and animal models, and more recently from clinical trials, indicate that PD-1/PD-1-ligand interactions are a major mechanism of immune suppression within the tumor microenvironment. Initial clinical studies of antibodies directed against PD-1 and B7-H1 demonstrated both an encouraging safety profile and remarkable antitumor activity in subsets of patients with metastatic disease including malignancies—such as lung cancer—which were previously thought to be unresponsive to immunotherapy. Preliminary data have suggested a correlation between tumor membrane B7-H1 expression and clinical response to anti-PD-1 antibodies. Several key challenges remain to optimize development of PD-1/B7-H1 pathway blockade, including defining the biological significance of all potential ligand-receptor interactions in the tumor microenvironment, developing more accurate predictive biomarkers of response, determining the breadth of activity in human malignancies, and developing rational combinations of therapy that address key mechanisms involved in positive and negative regulation of antitumor immune responses. PMID:23460533

  4. The Impact of PD-L1 Expression in Patients with Metastatic GEP-NETs.

    PubMed

    Kim, Seung Tae; Ha, Sang Yun; Lee, Sujin; Ahn, Soomin; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Kim, Kyoung-Mee; Park, Young Suk

    2016-01-01

    Programmed death-ligand 1 (PD-L1), which is expressed on many cancer cells, interacts with PD1 expressed on the surface of T cells, inhibiting the T cells and blocking the antitumor immune response. Expression of PD-L1 in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has not been studied. We investigated the impact of PD-L1 expression in 32 patients with metastatic GEP-NET. The expression of PD-L1 was evaluated using an anti-PD-L1 immunohistochemistry (IHC) antibody optimized for staining of formalin-fixed paraffin-embedded (FFPE) tissue samples. The correlation between PD-L1 and clinicopathological data including survival and response to systemic treatments was analyzed. Primary sites were 24 foregut-derived GEP-NETs, including stomach (n=1), duodenum (n=2), biliary tract (n=7), and pancreas (n=14), and 8 hindgut-derived GEP-NETs of the distal colon and rectum. Among the 32 patients with metastatic GEP-NET analyzed in this study, 7 (21.9%) had expression of PD-L1 in tumor tissues. Expression of PD-L1 was significantly associated with high-grade WHO classification (grade 3) (p=0.008) but not with gender, primary site, and number of metastatic sites (p>0.05). The status of PD-L1 expression was statistically associated with progression-free survival (PFS) for first-line systemic treatment (p=0.047). Moreover, the status of PD-L1 expression could significantly predict overall survival (p=0.037). The expression of PD-L1 was associated with higher WHO tumor grade (grade 3) in metastatic GEP-NETs. PD-L1 expression had both predictive and prognostic value for survival of patients with metastatic GEP-NETs. PMID:26958083

  5. Comparison of weight changes following unilateral and staged bilateral STN DBS for advanced PD

    PubMed Central

    Lee, Eric M; Kurundkar, Ashish; Cutter, Gary R; Huang, He; Guthrie, Barton L; Watts, Ray L; Walker, Harrison C

    2011-01-01

    Unilateral and bilateral subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson's disease (PD) result in weight gain in the initial postoperative months, but little is known about the changes in weight following unilateral and staged bilateral STN DBS over longer time intervals. A case–control comparison evaluated weight changes over 2 years in 43 consecutive unilateral STN DBS patients, among whom 25 elected to undergo staged bilateral STN DBS, and 21 age-matched and disease severity matched PD controls without DBS. Regression analyses incorporating age, gender, and baseline weight in case or control were conducted to assess weight changes 2 years after the initial unilateral surgery. Unilateral STN DBS and staged bilateral STN DBS patients gained 3.9 ± 2.0 kg and 5.6 ± 2.1 kg versus their preoperative baseline weight (P < 0.001, respectively) while PD controls without DBS lost 0.8 ± 1.1 kg. Although bilateral STN DBS patients gained 1.7 kg more than unilateral STN DBS patients at 2 years, this difference was not statistically significant (P = 0.885). Although there was a trend toward greater weight gain in staged bilateral STN DBS patients versus unilateral patients, we found no evidence for an equivalent or synergistic increase in body weight following placement of the second DBS electrode. PMID:22398977

  6. Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer.

    PubMed

    Dang, Thu Oanh; Ogunniyi, Adebayo; Barbee, Meagan S; Drilon, Alexander

    2016-01-01

    The emergence of immune checkpoint inhibitors marked an important advancement in the development of cancer therapeutics. Pembrolizumab is a selective humanized IgG4 kappa monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor, an integral component of immune checkpoint regulation in the tumor microenvironment. The drug is currently approved by the Food and Drug Administration for the treatment of advanced melanoma and metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC). Several published studies demonstrate that single-agent pembrolizumab is safe and has efficacy in patients with NSCLC. Many ongoing protocols are investigating the role of pembrolizumab in combination with other agents in lung cancer and various other cancer types. We review the available data on pembrolizumab in NSCLC and examine the role of potential predictive biomarkers of response to therapy.

  7. A novel sputtered Pd mesh architecture as an advanced electrocatalyst for highly efficient hydrogen production

    NASA Astrophysics Data System (ADS)

    de Lucas-Consuegra, Antonio; de la Osa, Ana R.; Calcerrada, Ana B.; Linares, José J.; Horwat, David

    2016-07-01

    This study reports the preparation, characterization and testing of a sputtered Pd mesh-like anode as an advanced electrocatalyst for H2 production from alkaline ethanol solutions in an Alkaline Membrane Electrolyzer (AEM). Pd anodic catalyst is prepared by magnetron sputtering technique onto a microfiber carbon paper support. Scanning Electron Microscopy images reveal that the used preparation technique enables to cover the surface of the carbon microfibers exposed to the Pd target, leading to a continuous network that also maintains part of the original carbon paper macroporosity. Such novel anodic architecture (organic binder free) presents an excellent electro-chemical performance, with a maximum current density of 700 mA cm-2 at 1.3 V, and, concomitantly, a large H2 production rate with low energy requirement compared to water electrolysis. Potassium hydroxide emerges as the best electrolyte, whereas temperature exerts the expected promotional effect up to 90 °C. On the other hand, a 1 mol L-1 ethanol solution is enough to guarantee an efficient fuel supply without any mass transfer limitation. The proposed system also demonstrates to remain stable over 150 h of operation along five consecutives cycles, producing highly pure H2 (99.999%) at the cathode and potassium acetate as the main anodic product.

  8. G6PD Deficiency Does Not Enhance Susceptibility for Acquiring Helicobacter pylori Infection in Sardinian Patients

    PubMed Central

    Dore, Maria Pina; Marras, Giuseppina; Rocchi, Chiara; Soro, Sara

    2016-01-01

    Background Subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency may be more susceptible to infections due to impaired leukocyte bactericidal activity. The disorder is common in the Mediterranean area. The aim of this study was to investigate whether G6PD deficiency may be a risk factor for acquiring H. pylori infection. Methods We performed a retrospective study. Data from clinical records of 6565 patients (2278 men and 4287 women, median age 51, range 7‒94) who underwent upper endoscopy between 2002 and 2014 were collected. H. pylori status, assessed by histology plus rapid urease test or 13C-urea breath test, and G6PD status were also reported. A multiple logistic regression model was used to investigate the association between G6PD deficiency and H. pylori infection. Results Enzyme deficiency was detected in 12% (789/6565) of the entire cohort, and more specifically in 8.3% of men and in 14.0% of women. Overall, the proportion of patients positive for H. pylori was 50.6% and 51.5% among G6PD deficient and non-deficient patients (χ² = 0.271; p = 0.315). Moreover, among G6PD-deficient and normal patients the frequency of previous H. pylori infection was similar. After adjustment for age and gender the risk for acquiring H. pylori infection was similar in G6PD-deficient and normal patients. Only age was a strong statistically significant risk predictor. Conclusions These results demonstrate for the first time that G6PD deficiency does not enhance patients’ susceptibility to acquire H. pylori infection in Sardinia. PMID:27467818

  9. Economic sustainability of anti-PD-1 agents nivolumab and pembrolizumab in cancer patients: Recent insights and future challenges.

    PubMed

    Tartari, Francesca; Santoni, Matteo; Burattini, Luciano; Mazzanti, Paola; Onofri, Azzurra; Berardi, Rossana

    2016-07-01

    Anti-programmed death (PD)-1 agents pembrolizumab and nivolumab have recently obtained enthusiastic results in terms of progression-free survival (PFS), overall survival (OS) and tolerability in cancer patients. Despite these promising data, the high cost of these agents needs careful consideration. Indeed, the evaluation of cost-effectiveness analysis (CEA) and quality-adjusted life year (QALY), as well as different drug reimbursement modalities, will represent fundamental tools in order to guarantee the economic sustainability of health system and the access to care for all cancer patients. In this review, we discussed the recent results obtained by immunotherapy in cancer patients and we evaluated the economic impact of recently approved nivolumab and pembrolizumab in patients with advanced melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC).

  10. Economic sustainability of anti-PD-1 agents nivolumab and pembrolizumab in cancer patients: Recent insights and future challenges.

    PubMed

    Tartari, Francesca; Santoni, Matteo; Burattini, Luciano; Mazzanti, Paola; Onofri, Azzurra; Berardi, Rossana

    2016-07-01

    Anti-programmed death (PD)-1 agents pembrolizumab and nivolumab have recently obtained enthusiastic results in terms of progression-free survival (PFS), overall survival (OS) and tolerability in cancer patients. Despite these promising data, the high cost of these agents needs careful consideration. Indeed, the evaluation of cost-effectiveness analysis (CEA) and quality-adjusted life year (QALY), as well as different drug reimbursement modalities, will represent fundamental tools in order to guarantee the economic sustainability of health system and the access to care for all cancer patients. In this review, we discussed the recent results obtained by immunotherapy in cancer patients and we evaluated the economic impact of recently approved nivolumab and pembrolizumab in patients with advanced melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). PMID:27310708

  11. Palliative peritoneal dialysis: Implementation of a home care programme for terminal patients treated with peritoneal dialysis (PD).

    PubMed

    Gorrin, Maite Rivera; Teruel-Briones, José Luis; Vion, Victor Burguera; Rexach, Lourdes; Quereda, Carlos

    2015-01-01

    Terminal-stage patients on peritoneal dialysis (PD) are often transferred to haemodialysis as they are unable to perform the dialysis technique themselves since their functional capacities are reduced. We present our experience with five patients on PD with a shortterm life-threatening condition, whose treatment was shared by primary care units and who were treated with a PD modality adapted to their circumstances, which we call Palliative Peritoneal Dialysis.

  12. [Increased expressions of programmed death 1 (PD-1) and its ligands in peripheral CD3(+) T cells and CD19(+) B cells in patients with hepatocellular carcinoma].

    PubMed

    Liu, Wei; Chai, Lin; Liang, Junli; Lu, Zhizhong; Yang, Siwei

    2016-09-01

    Objective To investigate the changes of programmed death 1 (PD-1) and ligands, as well as interferon-γ (IFN-γ) in peripheral blood mononuclear cells (PBMCs) of patients with hepatocellular carcinoma (HCC). Methods The peripheral blood was collected from 15 early HCC patients, 13 progressive HCC patients and 12 healthy volunteers. PBMCs was isolated from the peripheral blood. The expressions of PD-1, PD-L1 and PD-L2 in PBMCs were detected by flow cytometry; the serum level of IFN-γ was determined by ELISA; the correlation of PD-1 and IFN-γ was analyzed with Pearson's correlation and One-way ANOVA. Results The expression levels of PD-1, PD-L1 and PD-L2 in CD3(+) T cells and CD19(+) B cells and serum IFN-γ level in progressive HCC patients were significantly higher than those in the healthy group and early HCC patients. The expression levels of PD-1, PD-L1 and PD-L2 in the CD3(+) T cells and CD19(+) B cells of the HCC patients were positively correlated with IFN-γ. Conclusion The expression levels of PD-1, PD-L1 and PD-L2 increase in the PBMCs of HCC patients; PD-1 and PD-L1 are correlated with IFN-γ level. PMID:27609582

  13. Pembrolizumab for Treatment of Patients with Advanced or Unresectable Melanoma.

    PubMed

    Sullivan, Ryan J; Flaherty, Keith T

    2015-07-01

    From Coley's toxin to combination immune checkpoint inhibition, strategies to activate the immune system and generate anticancer immunity have been ongoing for well over a century. Over the past decade, the so-called immune checkpoint inhibitors, generally monoclonal antibodies that target key regulators of T-cell activation, emerged as the most effective immune-targeted agents. Pembrolizumab is the first anti-programmed death 1 (PD-1) antibody approved by the FDA for the treatment of metastatic melanoma. With responses seen in 25% to 40% of patients, depending on dose and setting (i.e., before or after ipilimumab), pembrolizumab specifically and anti-PD-1 antibodies generally are revolutionizing the treatment of melanoma. However, in the setting of other recent advances in the field, a number of practical issues are emerging that need to be addressed to optimize the care of patients with melanoma. First, the optimal sequencing of therapy (first-line immunotherapy over molecular targeted therapy, ipilimumab versus pembrolizumab as initial immune checkpoint inhibitor) is unknown and must be evaluated through randomized trials. Second, there is a strong rationale to combine immune checkpoint inhibitors (i.e., anti-PD-1 with ipilimumab) and to combine immune therapies with targeted therapy agents, so determining whether combination therapy is better than direct sequencing is another critical issue that needs to be addressed in carefully carried out studies.

  14. [Transarterial infusion chemotherapy using fine-powder cisplatin in patients with advanced hepatocellular carcinoma].

    PubMed

    Hatanaka, Takeshi; Kakizaki, Satoru; Ueno, Takashi; Takeuchi, Suguru; Takizawa, Daichi; Katakai, Kenji

    2014-02-01

    We investigated the therapeutic effects and safety of fine powder cisplatin for patients with advanced hepatocellular carcinoma( HCC). From January 2006 to March 2012, 123 patients with advanced HCC were treated by transarterial infusion chemotherapy(TAI)with fine-powder cisplatin(IA-call®, Nippon Kayaku Co. Ltd., Tokyo, Japan). The drug was infused into the liver through the feeding artery at a dose of 65 mg/m2. The treatment was repeated every 4 to 8 weeks until evidence of either tumor progression or unacceptable toxicity appeared. Treatment responses were classified as complete response(CR), partial response(PR), stable disease(SD), and progressive disease(PD)in 3.2%, 12.0%, 32.2%, and 52.4% of patients, respectively. The median survival durations were as follows: overall, 12.2 months; CR/PR patients, 23.8 months; and SD/PD patients, 10.6 months. The cumulative survival rates of CR/PR patients were significantly higher than those of SD/PD patients (p<0.05). Multivariate analyses revealed that treatment response, etiology, Child-Pugh grading, and level of protein induced by the vitamin K antagonist- II (PIVKA- II )were predictive factors of survival duration. Problematic adverse events were not observed in any of the patients. Our results suggest that TAI using fine-powder cisplatin can be safely administered for advanced HCC and can improve the prognosis of patients with advanced disease. PMID:24743198

  15. Serotonin Impairment in CSF of PD Patients, without an Apparent Clinical Counterpart

    PubMed Central

    Olivola, Enrica; Pierantozzi, Mariangela; Imbriani, Paola; Liguori, Claudio; Stampanoni Bassi, Mario; Conti, Marco; D′Angelo, Vincenza; Mercuri, Nicola Biagio; Stefani, Alessandro

    2014-01-01

    In Parkinson's disease (PD), several studies have detected an impaired serotonin (5-HT) pathway, likely affecting both motor and non-motor domains. However, the precise impact of 5-HT impairment is far from established. Here, we have used a HPLC chromatographic method, in a homogenous cohort (n = 35) of non fluctuating, non dyskinetic PD patients, to assess the concentration of 5-HT and its metabolite 5-HIAA in peripheral cerebrospinal fluid (CSF) obtained from lumbar puncture (LP). LP was performed following three days of therapy withdrawal, in order to vanish the effects of prolonged released dopamine agonists (DA), and in absence of any serotonergic agent. The PD patient group showed a significantly reduced CSF level of both 5-HT and 5-HIAA compared to either age-matched control subjects (n = 18), or Alzheimer's disease patients (n = 20). However, no correlation emerged between 5-HT/5-HIAA concentrations and UPDRS-III (r = −0.12), disease duration (r = −0.1), age (r = −0.27) and MMSE (r = 0.11). Intriguingly, low CSF 5-HT levels did not differ for gender or for motor phenotype (in terms of non-tremor dominant subtype and tremor dominant subtype). Further, low CSF 5-HT levels did not correlate with the presence of depression, apathy or sleep disturbance. Our findings support the contention that 5-HT impairment is a cardinal feature of stable PD, probably representing a hallmark of diffuse Lewy bodies deposition in the brainstem. However, clinical relevance remains uncertain. Given these findings, an add-on therapy with serotonergic agents seems questionable in PD patients, or should be individually tailored, unless severe depression is present. PMID:25036938

  16. Expression of PD-1 Molecule on Regulatory T Lymphocytes in Patients with Insulin-Dependent Diabetes Mellitus

    PubMed Central

    Perri, Valentina; Russo, Benedetta; Crinò, Antonino; Schiaffini, Riccardo; Giorda, Ezio; Cappa, Marco; Rosado, Maria Manuela; Fierabracci, Alessandra

    2015-01-01

    Type 1 diabetes is caused by autoreactive T cells that destroy pancreatic beta cells. Animal models suggested that a CD4+CD25+ population has a regulatory function capable of preventing activation and effector functions of autoreactive T cells. However, the role of CD4+CD25high T cells in autoimmunity and their molecular mechanisms remain the subject of investigation. We therefore evaluated T regulatory cell frequencies and their PD-1 expression in the peripheral blood of long-standing diabetics under basal conditions and after CD3/CD28 stimulation. Under basal conditions, the percentages of T regulatory cells were significantly higher while that of T effector cells were significantly lower in patients than in controls. The ratio of regulatory to effector T cells was higher in patients than that in controls, suggesting that T regulatory cells were functional in patients. Percentages of total PD-1+, PD-1low and PD-1high expressing T regulatory cells did not change in patients and in controls. After stimulation, a defect in T regulatory cell proliferation was observed in diabetics and the percentages of total PD-1+, PD-1low and PD-1high expressing cells were lower in patients. Our data suggest a defective activation of T regulatory cells in long-standing diabetics due to a lower expression of PD-1 on their surface. PMID:26393578

  17. Expression of PD-1 Molecule on Regulatory T Lymphocytes in Patients with Insulin-Dependent Diabetes Mellitus.

    PubMed

    Perri, Valentina; Russo, Benedetta; Crinò, Antonino; Schiaffini, Riccardo; Giorda, Ezio; Cappa, Marco; Rosado, Maria Manuela; Fierabracci, Alessandra

    2015-09-18

    Type 1 diabetes is caused by autoreactive T cells that destroy pancreatic beta cells. Animal models suggested that a CD4⁺CD25⁺ population has a regulatory function capable of preventing activation and effector functions of autoreactive T cells. However, the role of CD4⁺CD25high T cells in autoimmunity and their molecular mechanisms remain the subject of investigation. We therefore evaluated T regulatory cell frequencies and their PD-1 expression in the peripheral blood of long-standing diabetics under basal conditions and after CD3/CD28 stimulation. Under basal conditions, the percentages of T regulatory cells were significantly higher while that of T effector cells were significantly lower in patients than in controls. The ratio of regulatory to effector T cells was higher in patients than that in controls, suggesting that T regulatory cells were functional in patients. Percentages of total PD-1⁺, PD-1low and PD-1high expressing T regulatory cells did not change in patients and in controls. After stimulation, a defect in T regulatory cell proliferation was observed in diabetics and the percentages of total PD-1⁺, PD-1low and PD-1high expressing cells were lower in patients. Our data suggest a defective activation of T regulatory cells in long-standing diabetics due to a lower expression of PD-1 on their surface.

  18. Targeting the PD-1 pathway in patients with relapsed classic Hodgkin lymphoma following allogeneic stem cell transplant is safe and effective

    PubMed Central

    Villasboas, Jose Caetano; Ansell, Stephen M.; Witzig, Thomas E.

    2016-01-01

    Patients with classic Hodgkin lymphoma (cHL) that has relapsed after autologous or allogeneic transplant have limited treatment options and a poor prognosis. Immunotherapy with agents that target the PROGRAMMED DEATH 1 (PD-1) receptor have demonstrated clinical activity with durable responses in early-phase clinical trials in this patient population; however, patients with a history of allogeneic stem cell transplantation (SCT) were intentionally excluded from participation in those studies due to concerns for reactivation of graft-versus-host disease (GVHD). We describe the clinical course of two patients with advanced cHL and prior treatment with allogeneic stem cell transplantation (SCT) that were treated with the PD-1 inhibitor pembrolizumab. Both patients had no active graft-versus-host disease (GVHD) at the time initiation of therapy and were maintained on low-dose prednisone. Treatment with pembrolizumab was well tolerated and not associated with reactivation of GVHD. Both patients responded (1 partial, 1 complete) and remain on therapy as of November 30, 2015. This report indicates that immunotherapy targeting the PD-1 pathway can be safely administered to patients with cHL and a history of allogeneic SCT and produce tumor responses. Further studies in this patient population are needed. PMID:26848626

  19. A Report of Peritonitis from Aeromonas sobria in a Peritoneal Dialysis (PD) Patient with Necrotizing Fasciitis.

    PubMed

    Janma, Jirayut; Linasmita, Patcharasarn; Changsirikulchai, Siribha

    2015-11-01

    A 70-years of age, male patient with underlying type 2 diabetes mellitus, hypertension, dyslipidemia and ischemic heart disease had undergone continuous ambulatory peritoneal dialysis (CAPD)for 3 years without any episodes of peritonitis. He was diagnosed with necrotizing fasciitis and later developed peritonitis after receiving a laceration from an aquatic injury suffered during the flood disaster of 2011. The blood culture, necrotic tissue and the clear dialysate collected upon admission had shown Aeromonas sobria. The route of peritonitis may be from the hematogenous spread of A. sobria resulting in necrotizing fasciitis. A. sobria should be considered as the pathogen of peritonitis in PD patients who have history of wounds from contaminated water. We suggest that the PD patients who present with septicemia and did not meet the criteria for peritonitis, the initial dialysate effluent should be sent for culture. The benefit of this is to allow early recognition and treatment of peritonitis.

  20. Programmed Death Ligand 1 (PD-L1)-targeted TRAIL combines PD-L1-mediated checkpoint inhibition with TRAIL-mediated apoptosis induction.

    PubMed

    Hendriks, Djoke; He, Yuan; Koopmans, Iris; Wiersma, Valerie R; van Ginkel, Robert J; Samplonius, Douwe F; Helfrich, Wijnand; Bremer, Edwin

    2016-08-01

    Antibodies that block PD-L1/PD-1 immune checkpoints restore the activity of functionally-impaired antitumor T cells. These antibodies show unprecedented clinical benefit in various advanced cancers, particularly in melanoma. However, only a subset of cancer patients responds to current PD-L1/PD-1-blocking strategies, highlighting the need for further advancements in PD-L1/PD-1-based immunotherapy. Here, we report on a novel approach designed to combine PD-L1 checkpoint inhibition with the tumor-selective induction of apoptosis by TNF-related Apoptosis Inducing Ligand (TRAIL). In brief, a new bi-functional fusion protein, designated anti-PD-L1:TRAIL, was constructed comprising a PD-L1-blocking antibody fragment genetically fused to the extracellular domain of the pro-apoptotic tumoricidal protein TRAIL. Treatment of PD-L1-expressing cancer cells with anti-PD-L1:TRAIL induced PD-L1-directed TRAIL-mediated cancer cell death. Treatment of T cells with anti-PD-L1:TRAIL augmented T cell activation, as evidenced by increased proliferation, secretion of IFNγ and enhanced killing of cancer cell lines and primary patient-derived cancer cells in mixed T cell/cancer cell culture experiments. Of note, elevated levels of IFNγ further upregulated PD-L1 on cancer cells and simultaneously sensitized cancer cells to TRAIL-mediated apoptosis by anti-PD-L1:TRAIL. Additionally, anti-PD-L1:TRAIL converted immunosuppressive PD-L1-expressing myeloid cells into pro-apoptotic effector cells that triggered TRAIL-mediated cancer cell death. In conclusion, combining PD-L1 checkpoint inhibition with TRAIL-mediated induction of apoptosis using anti-PD-L1:TRAIL yields promising multi-fold and mutually reinforcing anticancer activity that may be exploited to enhance the efficacy of therapeutic PD-L1/PD-1 checkpoint inhibition. PMID:27622071

  1. PD-L1 polymorphism can predict clinical outcomes of non-small cell lung cancer patients treated with first-line paclitaxel-cisplatin chemotherapy

    PubMed Central

    Lee, Shin Yup; Jung, Deuk Kju; Choi, Jin Eun; Jin, Cheng Cheng; Hong, Mi Jeong; Do, Sook Kyung; Kang, Hyo-Gyoung; Lee, Won Kee; Seok, Yangki; Lee, Eung Bae; Jeong, Ji Yun; Shin, Kyung Min; Yoo, Seung Soo; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Park, Jae Yong

    2016-01-01

    This study was conducted to investigate whether polymorphisms of genes involved in immune checkpoints can predict the clinical outcomes of patients with advanced stage non-small cell lung cancer (NSCLC) after 1st line paclitaxel-cisplatin chemotherapy. A total of 379 NSCLC patients were enrolled. Twelve single nucleotide polymorphisms (SNPs) of PD-1, PD-L1, and CTLA-4 genes were selected and genotyped. The associations of SNPs with chemotherapy response and overall survival (OS) were analyzed. Among the 12 SNPs investigated, PD-L1 rs2297136T > C and rs4143815C > G were significantly associated with clinical outcomes after chemotherapy. The rs2297136T > C was significantly associated with both better chemotherapy response and better OS, and the rs4143815C > G had a significantly better response to chemotherapy. Consistent with the individual genotype analyses, rs2297136C-rs4143815G haplotype (ht4) carrying variant alleles at both loci was significantly associated with better chemotherapy response and OS compared with combined other haplotypes. Patients with at least one ht4 had significantly better chemotherapy response and OS compared to those without ht4. PD-L1 rs2297136T > C and rs4143815C > G polymorphisms may be useful for the prediction of clinical outcome of 1st line paclitaxel-cisplatin chemotherapy in NSCLC. Further studies are needed to confirm our findings and to understand the role of PD-L1 in the chemotherapy outcome of NSCLC patients. PMID:27181838

  2. Myelodysplastic Syndrome Revealed by Systems Immunology in a Melanoma Patient Undergoing Anti-PD-1 Therapy.

    PubMed

    Greenplate, Allison R; Johnson, Douglas B; Roussel, Mikael; Savona, Michael R; Sosman, Jeffrey A; Puzanov, Igor; Ferrell, P Brent; Irish, Jonathan M

    2016-06-01

    Antibodies aimed at blocking the interaction between programmed cell death-1 (PD-1) and its ligands have shown impressive efficacy in a variety of malignancies and are generally well tolerated. Research has focused intensely on T cells and their interaction with cells within melanoma tumors, while relatively little is understood about the systems immunology of the cells in the blood during checkpoint inhibitor therapy. Longitudinal cytomic analysis using mass cytometry can characterize all the cells in a small sample of blood and has the potential to reveal key shifts in the cellular milieu occurring during treatment. We report a case of advanced melanoma in which mass cytometry detected abnormal myeloid cells resulting from myelodysplastic syndrome (MDS) in the blood following treatment with an anti-PD-1 agent. Myeloid blasts comprised <1% of peripheral blood mononuclear cells (PBMC) 1 month after the start of treatment. Six months after starting therapy, myeloid blasts comprised 5% of PBMCs, and a bone marrow biopsy confirmed refractory anemia with excess blasts-2 (RAEB-2). Longitudinal mass cytometry immunophenotyping comprehensively characterized blast phenotype evolution and revealed elevated PD-1 expression on the surface of nonblast myeloid cells. These findings highlight the clinical significance of cytomic monitoring, indicate that the myeloid compartment should be monitored during checkpoint inhibitor therapy, and emphasize the value of systems immunology in medicine. Cancer Immunol Res; 4(6); 474-80. ©2016 AACR.

  3. Nanorods of Co/Pd multilayers fabricated by glancing angle deposition for advanced media

    SciTech Connect

    Su, Hao; Gupta, Subhadra; Natarajarathinam, Anusha

    2013-05-28

    Perpendicular anisotropy magnetic nanorods composed of Co/Pd multilayers have been successfully fabricated by glancing angle deposition (GLAD) in a planetary sputtering system. Co and Pd layer thickness, ratio, and bilayer number were optimized for both normal and GLAD depositions. Scanning electron micrographs estimated the nanorods to be about 12 nm in diameter. M-H loops showed that the coercivity for the GLAD nanorods increased from 1.3 kOe for the normally deposited continuous films to 2.9 kOe for the GLAD nanorod array, a 123% increase.

  4. PD1-Expressing T Cell Subsets Modify the Rejection Risk in Renal Transplant Patients

    PubMed Central

    Pike, Rebecca; Thomas, Niclas; Workman, Sarita; Ambrose, Lyn; Guzman, David; Sivakumaran, Shivajanani; Johnson, Margaret; Thorburn, Douglas; Harber, Mark; Chain, Benny; Stauss, Hans J.

    2016-01-01

    We tested whether multi-parameter immune phenotyping before or after renal ­transplantation can predict the risk of rejection episodes. Blood samples collected before and weekly for 3 months after transplantation were analyzed by multi-parameter flow cytometry to define 52 T cell and 13 innate lymphocyte subsets in each sample, producing more than 11,000 data points that defined the immune status of the 28 patients included in this study. Principle component analysis suggested that the patients with histologically confirmed rejection episodes segregated from those without rejection. Protein death 1 (PD-1)-expressing subpopulations of regulatory and conventional T cells had the greatest influence on the principal component segregation. We constructed a statistical tool to predict rejection using a support vector machine algorithm. The algorithm correctly identified 7 out of 9 patients with rejection, and 14 out of 17 patients without rejection. The immune profile before transplantation was most accurate in determining the risk of rejection, while changes of immune parameters after transplantation were less accurate in discriminating rejection from non-rejection. The data indicate that pretransplant immune subset analysis has the potential to identify patients at risk of developing rejection episodes, and suggests that the proportion of PD1-expressing T cell subsets may be a key indicator of rejection risk. PMID:27148254

  5. Ultrasound-Guided Regional Anesthesia in a Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Geriatric Trauma Patient

    PubMed Central

    Födinger, Agnes M.; Kammerlander, Christian; Luger, Thomas J.

    2012-01-01

    Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic enzymatic disorder causing hemolytic anemia. Exposure to drugs is considered to be the most common cause of acute hemolysis in patients with G6PD deficiency. Experience with regional anesthesia, in particular peripheral nerve blocks, is rarely described in patients with G6PD deficiency, but is of great clinical interest. For this reason, we now report on the successful management of ultrasound-guided axillary brachial plexus block in a patient with geriatric G6PD deficiency. Case report: A female, 75-year-old geriatric trauma patient with G6PD deficiency and a fracture of the left forearm, was scheduled for osteosynthesis of the left forearm. For surgery regional anesthesia with ultrasound-guided axillary brachial plexus block with 30 mL bupivacaine 0.5% was established. Surgical operation und postoperative course were uneventful and with no signs of hemolysis. Conclusion: Ultrasound-guided axillary brachial plexus block with bupivacaine was a safe and effective technique in this patient with G6PD deficiency. Peripheral nerve block is a major analgesic approach and of great value for anesthesiologists and surgeons, especially in our aging and multimorbid society. PMID:23569708

  6. Hypomethylation and up-regulation of PD-1 in T cells by azacytidine in MDS/AML patients: A rationale for combined targeting of PD-1 and DNA methylation.

    PubMed

    Ørskov, Andreas D; Treppendahl, Marianne B; Skovbo, Anni; Holm, Mette S; Friis, Lone S; Hokland, Marianne; Grønbæk, Kirsten

    2015-04-20

    The hypomethylating agents (HMAs) are standard therapy for patients with higher-risk myelodysplastic syndrome (MDS); however, the majority of the patients will lose their response to HMAs over time due to unknown mechanisms. It has recently been shown that T cell expression of the immunoinhibitory receptor PD-1 is regulated by DNA methylation. In 12 of 27 patients (44%) PD-1 promoter demethylation was observed in sorted peripheral blood T cells isolated over consecutive cycles of treatment with 5-azacytidine (5-aza). The PD-1 promoter demethylation correlated with an increase in PD-1 expression. Moreover, demethylation of the PD-1 promoter correlated with a significantly worse overall response rate (8% vs. 60%, p = 0.014), and a trend towards a shorter overall survival (p = 0.11) was observed. A significantly higher baseline methylation level of the PD-1 promoter was observed in T cells of non-responding patients compared to healthy controls (p = 0.023). Accordingly, in addition to their beneficial function, HMAs induce PD-1 expression on T cells in the MDS microenvironment, thereby likely hampering the immune response against the MDS blasts. Thus, we suggest that activation of the PD-1 checkpoint during HMA treatment can be a possible resistance mechanism, which may be overcome by combination therapy with a PD-1 pathway inhibitor. PMID:25823822

  7. Retinal vasculitis and ocular vitreous metastasis following complete response to PD-1 inhibition in a patient with metastatic cutaneous melanoma.

    PubMed

    Manusow, Joshua S; Khoja, Leila; Pesin, Nataly; Joshua, Anthony M; Mandelcorn, Efrem D

    2014-01-01

    We report on a 36-year-old woman treated with the anti PD-1 antibody Pembrolizumab for metastatic cutaneous melanoma in the first line setting. She achieved a complete response and then relapsed with metastases to the vitreous cavity with an associated angiographically determined retinal vasculitis. Vitreous metastasis without choroidal involvement is unusual and may be due to individual cell extravasation, vitreous hemorrhage containing malignant cells, or direct spread through the optic nerve. This finding highlights the need for immune sanctuary sites to be monitored in the presence of PD-1 inhibition and we hypothesize that the use of PD-1 inhibitor potentiated the patient's angiographically determined retinal vasculitis. PMID:25516805

  8. Decreased PD-1 positive blood follicular helper T cells in patients with psoriasis.

    PubMed

    Shin, Dongyun; Kim, Dae Suk; Kim, Sung Hee; Je, Jung Hwan; Kim, Hee Ju; Young Kim, Do; Kim, Soo Min; Lee, Min-Geol

    2016-10-01

    Follicular helper T (Tfh) cells are recently characterized subset of helper T cells, which are initially found in the germinal centers of B cell follicles. The major role of Tfh cells is helping B cell activation and antibody production during humoral immunity. Recently, blood Tfh cells were shown to be associated with autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, bullous pemphigoid and psoriasis. There is only one study which investigated Tfh cells in psoriasis patients. Therefore, in this study, we evaluated and analyzed blood Tfh cells in Korean patients with psoriasis. A total of 28 psoriasis patients and 16 healthy controls were enrolled. The frequency and absolute number of CXCR5(+)PD-1(+) Tfh cells were decreased in patients with psoriasis compared to healthy controls. CD4(+)CXCR5(+) T cells and CXCR5(+)ICOS(+) Tfh cells did not show differences. The frequency and absolute number of CXCR5(+)PD-1(+) Tfh cells in psoriasis patients negatively correlated with erythrocyte sedimentation rate and positively correlated with disease duration. The absolute number of CXCR5(+)ICOS(+) Tfh cells also showed positive correlation with disease duration. However, the subpopulations of Tfh cells did not correlate with Psoriasis Area and Severity Index. Serum interleukin-21 level was significantly increased in psoriasis patients compared to healthy controls, however, its level did not correlate with clinical and experimental parameters of psoriasis patients. These findings suggest the decreased function of Tfh cells in psoriasis, which could result in attenuated B cell immune responses in the pathogenesis of psoriasis. However, further investigations are necessary to confirm the function of Tfh cells in psoriasis vulgaris. PMID:27501809

  9. Incidence and risk of hepatic toxicities with PD-1 inhibitors in cancer patients: a meta-analysis

    PubMed Central

    Zhang, Xi; Ran, Yuge; Wang, Kunjie; Zhu, Yuanxue; Li, Jinghua

    2016-01-01

    Purpose Anti-programmed cell death receptor-1 (PD-1) antibodies have demonstrated antitumor activity in many cancer entities. Hepatic adverse events (AEs) are one of its major side effects, but the overall risks have not been systematically evaluated. Thus, we conducted this meta-analysis to investigate the overall incidence and risk of developing hepatic AEs in cancer patients treated with PD-1 inhibitors. Methods PubMed, Embase, and oncology conference proceedings were searched for relevant studies. Eligible studies were randomized controlled trials of cancer patients treated with PD-1 inhibitors with adequate data on hepatic AEs. Results A total of nine randomized controlled trials with a variety of solid tumors were eligible for the meta-analysis. The use of PD-1 inhibitors significantly increased the risk of developing all-grade hepatic AEs but not for high-grade hepatic AEs in comparison with chemotherapy or everolimus control. Additionally, the risk of all-grade and high-grade hepatic AEs with a nivolumab/ipilimumab combination was substantially higher than ipilimumab. No significant differences in the risk of all-grade and high-grade hepatic AEs were found between PD-1 inhibitors monotherapy and ipilimumab. Conclusion While the use of PD-1 inhibitors is associated with an increased risk of developing hepatic AEs in cancer patients, this is primarily for lower grade events. PMID:27729774

  10. A Phase III Study of Durvalumab (MEDI4736) With or Without Tremelimumab for Previously Treated Patients With Advanced NSCLC: Rationale and Protocol Design of the ARCTIC Study.

    PubMed

    Planchard, David; Yokoi, Takashi; McCleod, Michael J; Fischer, Jürgen R; Kim, Young-Chul; Ballas, Marc; Shi, Kelvin; Soria, Jean-Charles

    2016-05-01

    Anti-programmed cell death-1 and anti-programmed cell death ligand-1 (PD-L1) monotherapies have shown promising clinical activity in advanced, refractory non-small-cell lung cancer (NSCLC), but antitumor activity appears to be greater in patients with PD-L1(+) tumors compared with patients harboring PD-L1(-) tumors. Combining the anti-PD-L1 antibody durvalumab and the anti-cytotoxic T-lymphocyte antigen 4 antibody tremelimumab offers the potential for antitumor activity in patients with advanced NSCLC, regardless of PD-L1 tumor status. ARCTIC (NCT02352948) is a global, phase III, randomized, open-label multicenter study in patients with advanced NSCLC assessing the safety and clinical activity of durvalumab versus standard of care (SoC; erlotinib, gemcitabine, or vinorelbine) in patients with PD-L1(+) tumors (≥25% of tumor cells with membrane staining using VENTANA PD-L1 [SP263] CDx Assay) (Sub-study A) and the combination of durvalumab + tremelimumab or either agent as monotherapy versus SoC in patients with PD-L1(-) tumors (Sub-study B). Eligible patients are those with locally advanced or metastatic NSCLC (Stage IIIB/IV), without epidermal growth factor receptor tyrosine kinase activating mutations or anaplastic lymphoma kinase rearrangements, who have received at least 2 prior systemic regimens, including 1 platinum-based chemotherapy regimen. Co-primary endpoints are progression-free survival and overall survival. Secondary endpoints include the proportion of patients alive at 12 months, objective response rate, duration of response, progression-free survival at 6 and 12 months, safety and tolerability, pharmacokinetics, immunogenicity, and quality of life. The exploratory endpoints will assess potential biomarkers of treatment response. Recruitment started in January 2015 and is ongoing. PMID:27265743

  11. A Phase III Study of Durvalumab (MEDI4736) With or Without Tremelimumab for Previously Treated Patients With Advanced NSCLC: Rationale and Protocol Design of the ARCTIC Study.

    PubMed

    Planchard, David; Yokoi, Takashi; McCleod, Michael J; Fischer, Jürgen R; Kim, Young-Chul; Ballas, Marc; Shi, Kelvin; Soria, Jean-Charles

    2016-05-01

    Anti-programmed cell death-1 and anti-programmed cell death ligand-1 (PD-L1) monotherapies have shown promising clinical activity in advanced, refractory non-small-cell lung cancer (NSCLC), but antitumor activity appears to be greater in patients with PD-L1(+) tumors compared with patients harboring PD-L1(-) tumors. Combining the anti-PD-L1 antibody durvalumab and the anti-cytotoxic T-lymphocyte antigen 4 antibody tremelimumab offers the potential for antitumor activity in patients with advanced NSCLC, regardless of PD-L1 tumor status. ARCTIC (NCT02352948) is a global, phase III, randomized, open-label multicenter study in patients with advanced NSCLC assessing the safety and clinical activity of durvalumab versus standard of care (SoC; erlotinib, gemcitabine, or vinorelbine) in patients with PD-L1(+) tumors (≥25% of tumor cells with membrane staining using VENTANA PD-L1 [SP263] CDx Assay) (Sub-study A) and the combination of durvalumab + tremelimumab or either agent as monotherapy versus SoC in patients with PD-L1(-) tumors (Sub-study B). Eligible patients are those with locally advanced or metastatic NSCLC (Stage IIIB/IV), without epidermal growth factor receptor tyrosine kinase activating mutations or anaplastic lymphoma kinase rearrangements, who have received at least 2 prior systemic regimens, including 1 platinum-based chemotherapy regimen. Co-primary endpoints are progression-free survival and overall survival. Secondary endpoints include the proportion of patients alive at 12 months, objective response rate, duration of response, progression-free survival at 6 and 12 months, safety and tolerability, pharmacokinetics, immunogenicity, and quality of life. The exploratory endpoints will assess potential biomarkers of treatment response. Recruitment started in January 2015 and is ongoing.

  12. Clinical Impact and Cost-Effectiveness of an Education Program for PD Patients: A Randomized Controlled Trial

    PubMed Central

    Ory-Magne, Fabienne; Arcari, Céline; Mohara, Christine; Pourcel, Laure; Derumeaux, Hélène; Bérard, Emilie; Bourrel, Robert; Molinier, Laurent; Brefel-Courbon, Christine

    2016-01-01

    Background Parkinson’s disease (PD) is characterized by its impact on quality of life, constituting a substantial economic burden on society. Education programs implicating patients more in the management of their illness and complementing medical treatment may be a beneficial adjunct in PD. This study assessed the impact of an education program on quality of life and its cost-effectiveness in PD patients. Methods This single-center, prospective, randomized study assessed an education program consisting of individual and group sessions over a 12-month period. A total of 120 PD patients were assigned to either the Treated by Behavioral Intervention group (TTBI) or the no TTBI group. The primary outcome criterion was quality of life assessed using PDQ39. The Unified Parkinson’s Disease Rating Scale (UPDRS) and psychological status were collected. An economic evaluation was performed, including calculations of incremental cost-effectiveness ratios (ICERs). Results After 12 months of follow-up, changes recorded in the PDQ39 between the groups were not significantly different but better changes were observed in each dimension in the TTBI group compared to the no TTBI group. UPDRS I, II and total score were significantly improved in TTBI group compared to the no TTBI group. Mean annual costs did not differ significantly between the two groups. Conclusion This study suggested that the education program positively impacts the perceived health of PD patients without increasing medical costs. PMID:27685455

  13. Recent advance in patient monitoring

    PubMed Central

    2010-01-01

    Recent advance in technology has developed a lot of new aspects of clinical monitoring. We can monitor sedation levels during anesthesia using various electroencephalographic (EEG) indices, while it is still not useful for anesthesia depth monitoring. Some attempts are made to monitor the changes in sympathetic nerve activity as one of the indicators of stress, pain/analgesia, or anesthesia. To know the balance of sympathetic and parasympathetic activity, heart rate or blood pressure variability is investigated. For trend of cardiac output, low invasive monitors have been investigated. Improvement of ultrasound enables us to see cardiac structure and function continuously and clearer, increases success rate and decreases complication of central venous puncture and various kinds of nerve blocks. Without inserting an arterial catheter, trends of arterial oxygen tension or carbon dioxide tension can be monitored. Indirect visualization of the airway decreases difficult intubation and makes it easier to teach tracheal intubation. The changes in blood volume can be speculated non-invasively. Cerebral perfusion and metabolism are not ordinary monitored yet, but some studies show their usefulness in management of critically ill. This review introduces recent advances in various monitors used in anesthesia and critical care including some studies of the author, especially focused on EEG and cardiac output. However, the most important is that these new monitors are not almighty but should be used adequately in a limited situation where their meaning is confirmed. PMID:20877698

  14. Increased soluble and membrane-bound PD-L1 contributes to immune regulation and disease progression in patients with tuberculous pleural effusion

    PubMed Central

    Pan, Xue; Zhong, Anyuan; Xing, Yufei; Shi, Minhua; Qian, Bin; Zhou, Tong; Chen, Yongjing; Zhang, Xueguang

    2016-01-01

    Soluble and membrane-bound programmed death ligand-1 (sPD-L1 and mPD-L1, respectively) have been demonstrated to participate in the immune suppression of non-small cell lung cancer. However, the contribution of sPD-L1 and mPD-L1 to immune regulation and disease progression in patients with pleural effusions remains unknown. The present study evaluated the levels of sPD-L1 and membrane-bound PD-1/PD-L1 in the peripheral blood and pleural effusions of patients with tuberculous pleural effusion (TPE), malignant pleural effusion (MPE) and non-tuberculous non-malignant pleural effusion (n-TB n-M). Furthermore, selected T lymphocytes and cluster of differentiation (CD)14+ monocytes were co-cultured to investigate the potential effect of the PD-1/PD-L1 pathway in TPE. Levels of sPD-L1 and PD-L1 on CD14+ monocytes were increased in the TPE group, as compared with the MPE and n-TB n-M groups. Furthermore, sPD-L1 levels and the expression levels of PD-L1 on CD14+ monocytes were demonstrated to be positively correlated with interferon (IFN)-γ concentration in pleural effusions. Therefore, IFN-γ may increase the expression of PD-L1 on CD14+ monocytes in vitro. Cell counting kit-8 analysis demonstrated that anti-PD-L1 antibody was able to partially reverse the proliferation of T lymphocytes in the co-culture system. The results of the present study indicated that sPD-L1 or mPD-L1 are associated with the immune regulation and disease progression of TPE, and may serve as possible biomarkers of TPE. Furthermore, sPD-L1 and the PD-1/PD-L1 pathway of TPE may be associated with the Th1 immune response; therefore, an anti-PD-1/PD-L1 pathway suggests a potential immune therapy strategy for the treatment of TPE. PMID:27698705

  15. Increased soluble and membrane-bound PD-L1 contributes to immune regulation and disease progression in patients with tuberculous pleural effusion

    PubMed Central

    Pan, Xue; Zhong, Anyuan; Xing, Yufei; Shi, Minhua; Qian, Bin; Zhou, Tong; Chen, Yongjing; Zhang, Xueguang

    2016-01-01

    Soluble and membrane-bound programmed death ligand-1 (sPD-L1 and mPD-L1, respectively) have been demonstrated to participate in the immune suppression of non-small cell lung cancer. However, the contribution of sPD-L1 and mPD-L1 to immune regulation and disease progression in patients with pleural effusions remains unknown. The present study evaluated the levels of sPD-L1 and membrane-bound PD-1/PD-L1 in the peripheral blood and pleural effusions of patients with tuberculous pleural effusion (TPE), malignant pleural effusion (MPE) and non-tuberculous non-malignant pleural effusion (n-TB n-M). Furthermore, selected T lymphocytes and cluster of differentiation (CD)14+ monocytes were co-cultured to investigate the potential effect of the PD-1/PD-L1 pathway in TPE. Levels of sPD-L1 and PD-L1 on CD14+ monocytes were increased in the TPE group, as compared with the MPE and n-TB n-M groups. Furthermore, sPD-L1 levels and the expression levels of PD-L1 on CD14+ monocytes were demonstrated to be positively correlated with interferon (IFN)-γ concentration in pleural effusions. Therefore, IFN-γ may increase the expression of PD-L1 on CD14+ monocytes in vitro. Cell counting kit-8 analysis demonstrated that anti-PD-L1 antibody was able to partially reverse the proliferation of T lymphocytes in the co-culture system. The results of the present study indicated that sPD-L1 or mPD-L1 are associated with the immune regulation and disease progression of TPE, and may serve as possible biomarkers of TPE. Furthermore, sPD-L1 and the PD-1/PD-L1 pathway of TPE may be associated with the Th1 immune response; therefore, an anti-PD-1/PD-L1 pathway suggests a potential immune therapy strategy for the treatment of TPE.

  16. Numbers of CD8+PD-1+ and CD4+PD-1+ Cells in Peripheral Blood of Patients with Chronic Lymphocytic Leukemia Are Independent of Binet Stage and Are Significantly Higher Compared to Healthy Volunteers.

    PubMed

    Novák, Martin; Procházka, Vit; Turcsányi, Peter; Papajík, Tomáš

    2015-01-01

    The programmed cell death pathway is involved in functional impairment of cytotoxic CD8+ T cells in chronic viral infection and in tumor immune evasion. The interaction of programmed cell death-1 (PD-1) with its ligand suppresses antitumor T cell function and stimulates the regulatory T cell population. The objectives were to investigate whether examining PD-1 expression in peripheral T cells of patients with chronic lymphocytic leukemia (CLL) reflected the disease phase and Binet stage and to compare the results with those in healthy volunteers. The study analyzed peripheral blood from previously untreated patients with CLL, patients with relapsed or refractory disease under treatment and healthy blood donors using flow cytometry. PD-1 expression in peripheral blood CD4+ and CD8+ cells was markedly different between disease stages and in comparison with healthy subjects. The highest numbers of both CD8+PD-1+ and CD4+PD-1+ cells were present in patients with relapsed/refractory disease. No distinct difference according to Binet stage was found. These facts support the hypothesis that tumor clones may switch effector CD8+ cells through the PD-1/PD-1L pathway into an immunotolerant state. The extent to which the mechanisms of antitumor immunity are influenced by enhanced expression of the programmed cell death depends on the disease phase but not Binet stage.

  17. Analgesia for patients with advanced disease: 2

    PubMed Central

    Hall, E; Sykes, N

    2004-01-01

    The first article in this series explored epidemiology and patterns of pain in advanced disease, non-pharmacological treatments, and the use of opioids to manage pain. This second article examines the use of non-opioid drugs and anaesthetic interventions for pain relief in advanced disease. It also discusses an approach to managing analgesia in dying patients and finally looks at future developments. PMID:15082837

  18. Bilateral subthalamic stimulation monotherapy in advanced Parkinson's disease: long-term follow-up of patients.

    PubMed

    Valldeoriola, Francesc; Pilleri, Manuela; Tolosa, Eduardo; Molinuevo, José L; Rumià, Jordi; Ferrer, Enric

    2002-01-01

    Bilateral subthalamic nucleus stimulation (STN-DBS) is used to improve parkinsonian symptoms and attenuate levodopa-induced motor complications. In some patients, such clinical improvement allows antiparkinsonian medication (ApMed) withdrawal. We show the clinical outcome at the long-term follow-up of patients with advanced Parkinson's disease (PD) in which STN-DBS was used in monotherapy, and compare the clinical results of patients without medication with those obtained in parkinsonian patients in which ApMed were reduced but could not be totally displaced after surgery. We analyzed clinical outcome of ten patients with PD in which all ApMed was withdrawn after bilateral subthalamic stimulation and 16 parkinsonian patients still taking antiparkinsonian medication after surgery. After 1.5 years, STN-DBS monotherapy produced UPDRS motor scores similar to those observed in the on-drug condition before surgery without the inconvenience of motor fluctuations and dyskinesias. No significant differences were seen in most of clinical outcome measures when comparing patients still taking ApMed with patients in STN-DBS monotherapy but a few patients still taking ApMed presented mild dyskinesias and motor fluctuations and patients with STN-DBS monotherapy did not. STN-DBS is useful in the treatment of advanced PD and in some patients it is possible to maintain this therapy alone in the long term. The therapeutic effect of STN-DBS on motor signs can be equipotent to that of levodopa with the additional benefit of avoiding motor fluctuations and dyskinesias.

  19. The Efficacy of Continued Sorafenib Treatment after Radiologic Confirmation of Progressive Disease in Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    2016-01-01

    Background Whether radiologically detected progressive disease (PD) is an accurate metric for discontinuing sorafenib treatment in patients with hepatocellular carcinoma (HCC) is unclear. We investigated the efficacy of sorafenib treatment after radiologic confirmation of PD in patients with advanced HCC. Methods We retrospectively analyzed HCC patients treated with sorafenib at Kyushu Medical Center. Six of the 92 patients with radiologically confirmed PD were excluded because they were classified as Child-Pugh C or had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3; 86 patients were ultimately enrolled. Results Among the 86 patients, 47 continued sorafenib treatment after radiologic confirmation of PD (the continuous group), whereas 39 did not (the discontinuous group). The median survival time (MST) in the continuous group after confirmation was 12.9 months compared with 4.5 months in the discontinuous group (p <0.01). The time to progression in the continuous group after confirmation was 2.6 months compared with 1.4 months in the discontinuous group (p <0.01); it was 4.2 months and 2.1 months in patients who had received sorafenib ≥4 months and <4 months, respectively, before confirmation (p = 0.03). In these subgroups, the post-PD MST was 16.7 months and 9.6 months, respectively (p < 0.01). Independent predictors of overall survival after radiologic detection of PD were (hazard ratio, confidence interval): ECOG PS <2 (0.290, 0.107–0.880), Barcelona Clinical Liver Cancer stage B (0.146, 0.047–0.457), serum α-fetoprotein level ≥400 ng/mL (2.801, 1.355–5.691), and post-PD sorafenib administration (0.279, 0.150–0.510). Conclusion Continuing sorafenib treatment after radiologic confirmation of PD increased survival in patients with advanced HCC. Therefore, radiologically detected PD is not a metric for discontinuation of sorafenib treatment in such patients. PMID:26745625

  20. Higher Frequency of Circulating PD-1(high) CXCR5(+)CD4(+) Tfh Cells in Patients with Chronic Schistosomiasis.

    PubMed

    Zhang, Yumei; Jiang, Yanyan; Wang, Yanjuan; Liu, Hua; Shen, Yujuan; Yuan, Zhongying; Hu, Yuan; Xu, Yuxin; Cao, Jianping

    2015-01-01

    The current knowledge of immunological responses to schistosomiasis is insufficient for the development of vaccine and therapies. The role of T follicular helper (Tfh) cells in schistosome infections is not fully defined. The frequency of circulating Tfh cells and serum cytokine levels were analyzed in 11 patients with chronic schistosomiasis and 10 healthy controls (HC), who reside in an endemic area for Schistosomiasis japonicum. Significantly higher frequencies of circulating CXCR5(+) CD4(+) Tfh cells and higher expression levels of ICOS and PD-1 in CXCR5(+) CD4(+) Tfh cells were observed in patients with chronic schistosomiasis compared to HC. The levels of IL-21 in serum and the expression of IL-21 mRNA were higher in chronic schistosomiasis patients than in HC. Moreover, the frequency of circulating PD-1(high) CXCR5(+) CD4(+) Tfh cells positively correlated with the levels of IL-21 in serum from patients with chronic schistosomiasis. A positive correlation was also found between the frequency of PD-1(high) CXCR5(+) CD4(+) Tfh cells and the levels of soluble egg antigen (SEA)-specific antibodies in serum samples from the patient group. Our study is the first regarding Tfh cells in chronic human schistosomiasis and the finding indicate that PD-1(high) CXCR5(+) CD4(+)Tfh cells might play an important role in the production of specific antibodies in schistosomiasis. This study contributes to the understanding of immune response to schistosomiasis and may provide helpful support in vaccine development.

  1. Visceral fat area is associated with HbA1c but not dialysate-related glucose load in nondiabetic PD patients

    NASA Astrophysics Data System (ADS)

    Ho, Li-Chun; Yen, Chung-Jen; Chao, Chia-Ter; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2015-08-01

    Factors associated with increased visceral fat area (VFA) have been well documented in the general population but rarely explored in nondiabetic individuals on peritoneal dialysis (PD). As glycosylated hemoglobin (HbA1c) is positively correlated with VFA in diabetic patients, we hypothesized that the same correlation would exist in nondiabetic PD patients. We enrolled 105 nondiabetic patients who had undergone chronic PD for more than 3 months. Each subject underwent an abdominal computed tomography (CT) scan, and the umbilicus cut was analyzed for VFA. VFA values, corrected for body mass index and subjected to natural logarithm transformations, were examined to determine whether they were correlated with HbA1c and other parameters. PD dialysates prescribed at the time of enrollment were recorded to calculate glucose load. We found that when 105 nondiabetic PD patients were classified according to tertiles of HbA1c, higher HbA1c was associated with larger VFA. Multiple linear regression analysis revealed that HbA1c was an independent determinant of VFA, while glucose load and other PD-specific factors were not. In summary, HbA1c, but not PD-related glucose load, was positively correlated with VFA in nondiabetic PD patients, suggesting clinical utility of HbA1c in the PD population.

  2. PD-L1 expression as a predictive biomarker for cytokine-induced killer cell immunotherapy in patients with hepatocellular carcinoma.

    PubMed

    Chen, Chang-Long; Pan, Qiu-Zhong; Zhao, Jing-Jing; Wang, Ying; Li, Yong-Qiang; Wang, Qi-Jing; Pan, Ke; Weng, De-Sheng; Jiang, Shan-Shan; Tang, Yan; Zhang, Xiao-Fei; Zhang, Hong-Xia; Zhou, Zi-Qi; Zeng, Yi-Xin; Xia, Jian-Chuan

    2016-07-01

    Cytokine-induced killer (CIK) cell immunotherapy represents an effective treatment strategy for treating hepatocellular carcinoma (HCC). However, the therapeutic benefits of CIK cell treatment can be influenced by differences in complex immune microenvironment between patients. Herein, we investigated the relationship between PD-L1 expression and survival benefits of CIK cell immunotherapy in HCC patients. This retrospective study included 448 HCC patients: 217 cases underwent hepatectomy alone; 231 cases received hepatectomy and post-operative CIK cell transfusion. Immunohistochemistry was used to measure PD-L1 expression in tumor tissue sections from all patients. Meanwhile, flow cytometry was performed to explore the relationship between PD-L1 expression and localized inflammatory response in HCC microenvironment. We found a significantly improved prognosis in CIK treatment group compared with surgery alone group. In the CIK treatment group, higher PD-L1 expression was observed in patients who exhibited long-term survival benefit. Survival analysis showed patients with ≥5% PD-L1 expression had better overall survival (OS) and recurrence-free survival (RFS) than patients with 1-5% or <1% PD-L1 expression, particularly in the subgroup with high hepatitis B viral load. By contrast, PD-L1 expression did not show direct impact on the survival of patients in surgery alone group. Additionally, PD-L1 expression was found to be highly associated with hepatitis B viral load and the proportion of tumor-infiltrating lymphocytes in HCC patients. In conclusions, our study indicates that PD-L1 expression may reflect the presence of endogenous host immune response to tumor and serve as a biomarker for predicting survival benefits from adjuvant CIK cell immunotherapy in HCC patients. PMID:27622026

  3. Potential role of nuclear PD-L1 expression in cell-surface vimentin positive circulating tumor cells as a prognostic marker in cancer patients

    PubMed Central

    Satelli, Arun; Batth, Izhar Singh; Brownlee, Zachary; Rojas, Christina; Meng, Qing H.; Kopetz, Scott; Li, Shulin

    2016-01-01

    Although circulating tumor cells (CTCs) have potential as diagnostic biomarkers for cancer, determining their prognostic role in cancer patients undergoing treatment is a challenge. We evaluated the prognostic value of programmed death-ligand 1 (PD-L1) expression in CTCs in colorectal and prostate cancer patients undergoing treatment. Peripheral blood samples were collected from 62 metastatic colorectal cancer patients and 30 metastatic prostate cancer patients. CTCs were isolated from the samples using magnetic separation with the cell-surface vimentin(CSV)-specific 84-1 monoclonal antibody that detects epithelial-mesenchymal transitioned (EMT) CTCs. CTCs were enumerated and analyzed for PD-L1 expression using confocal microscopy. PD-L1 expression was detectable in CTCs and was localized in the membrane and/or cytoplasm and nucleus. CTC detection alone was not associated with poor progression-free or overall survival in colorectal cancer or prostate cancer patients, but nuclear PD-L1 (nPD-L1) expression in these patients was significantly associated with short survival durations. These results demonstrated that nPD-L1 has potential as a clinically relevant prognostic biomarker for colorectal and prostate cancer. Our data thus suggested that use of CTC-based models of cancer for risk assessment can improve the standard cancer staging criteria and supported the incorporation of nPD-L1 expression detection in CTCs detection in such models. PMID:27363678

  4. Inflammation Biomarkers of Advanced Disease in Nongingival Tissues of Chronic Periodontitis Patients

    PubMed Central

    da Costa, Thiago Alvares; Silva, Marcelo José Barbosa; Alves, Polyanna Miranda; Chica, Javier Emílio Lazo; Barcelos, Emilio Zorzo; Giani, Max Antonio Alves; Garlet, Gustavo Pompermaier; da Silva, João Santana; Rodrigues Júnior, Virmondes; Rodrigues, Denise Bertulucci Rocha; Cardoso, Cristina Ribeiro de Barros

    2015-01-01

    Chronic periodontitis is a multifactorial inflammatory disease that affects supporting structures of the teeth. Although the gingival response is largely described, little is known about the immune changes in the alveolar bone and neighboring tissues that could indicate periodontal disease (PD) activity. Then, in this study we identified the ongoing inflammatory changes and novel biomarkers for periodontitis in the tissues directly affected by the destructive disease in PD patients. Samples were collected by osteotomy in 17 control subjects during extraction of third molars and 18 patients with advanced PD, in which alveoloplasty was necessary after extraction of teeth with previous extensive periodontal damage. Patients presented mononuclear cells infiltration in the connective tissue next to the bone and higher fibrosis area, along with increased accumulation of IL-17+ and TRAP+ cells. The levels of TNF-α and MMP-2 mRNA were also elevated compared to controls and a positive and significant correlation was observed between TNF-α and MMP-2 mRNA expression, considering all samples evaluated. In conclusion, nongingival tissues neighboring large periodontal pockets present inflammatory markers that could predict ongoing bone resorption and disease spreading. Therefore, we suggested that the detailed evaluation of these regions could be of great importance to the assessment of disease progression. PMID:26063981

  5. Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson's disease (PD SURG trial): a randomised, open-label trial

    PubMed Central

    Williams, Adrian; Gill, Steven; Varma, Thelekat; Jenkinson, Crispin; Quinn, Niall; Mitchell, Rosalind; Scott, Richard; Ives, Natalie; Rick, Caroline; Daniels, Jane; Patel, Smitaa; Wheatley, Keith

    2010-01-01

    Summary Background Surgical intervention for advanced Parkinson's disease is an option if medical therapy fails to control symptoms adequately. We aimed to assess whether surgery and best medical therapy improved self-reported quality of life more than best medical therapy alone in patients with advanced Parkinson's disease. Methods The PD SURG trial is an ongoing randomised, open-label trial. At 13 neurosurgical centres in the UK, between November, 2000, and December, 2006, patients with Parkinson's disease that was not adequately controlled by medical therapy were randomly assigned by use of a computerised minimisation procedure to immediate surgery (lesioning or deep brain stimulation at the discretion of the local clinician) and best medical therapy or to best medical therapy alone. Patients were analysed in the treatment group to which they were randomised, irrespective of whether they received their allocated treatment. The primary endpoint was patient self-reported quality of life on the 39-item Parkinson's disease questionnaire (PDQ-39). Changes between baseline and 1 year were compared by use of t tests. This trial is registered with Current Controlled Trials, number ISRCTN34111222. Findings 366 patients were randomly assigned to receive immediate surgery and best medical therapy (183) or best medical therapy alone (183). All patients who had surgery had deep brain stimulation. At 1 year, the mean improvement in PDQ-39 summary index score compared with baseline was 5·0 points in the surgery group and 0·3 points in the medical therapy group (difference −4·7, 95% CI −7·6 to −1·8; p=0·001); the difference in mean change in PDQ-39 score in the mobility domain between the surgery group and the best medical therapy group was −8·9 (95% CI −13·8 to −4·0; p=0·0004), in the activities of daily living domain was −12·4 (−17·3 to −7·5; p<0·0001), and in the bodily discomfort domain was −7·5 (−12·6 to −2·4; p=0·004). Differences

  6. Diabetes Drug Victoza Might Not Help Advanced Heart Failure Patients

    MedlinePlus

    ... html Diabetes Drug Victoza Might Not Help Advanced Heart Failure Patients Study participants may have been too sick ... to improve heart function in patients with advanced heart failure, a new study finds. The theory for this ...

  7. DNA damage and apoptosis in mononuclear cells from glucose-6-phosphate dehydrogenase-deficient patients (G6PD Aachen variant) after UV irradiation.

    PubMed

    Efferth, T; Fabry, U; Osieka, R

    2001-03-01

    Patients affected with X chromosome-linked, hereditary glucose-6-phosphate dehydrogenase (G6PD) deficiency suffer from life-threatening hemolytic crises after intake of certain drugs or foods. G6PD deficiency is associated with low levels of reduced glutathione. We analyzed mononuclear white blood cells (MNC) of three males suffering from the German G6PD Aachen variant, four heterozygote females of this family, one G6PD-deficient male from another family coming from Iran, and six healthy male volunteers with respect to their DNA damage in two different genes (G6PD and T-cell receptor-delta) and their propensity to enter apoptosis after UV illumination (0.08-5.28 J/cm2). As determined by PCR stop assays, there was more UV-induced DNA damage in MNC of G6PD-deficient male patients than in those of healthy subjects. MNC of G6PD-deficient patients showed a higher rate of apoptosis after UV irradiation than MNC of healthy donors. MNC of heterozygote females showed intermediate rates of DNA damage and apoptosis. It is concluded that increased DNA damage may be a result of deficient detoxification of reactive oxygen species by glutathione and may ultimately account for the higher rate of apoptosis in G6PD-deficient MNC.

  8. Evaluation of PD-L1 Expression in Tumor Tissue of Patients with Lung Carcinoma and Correlation with Clinical and Demographic Data

    PubMed Central

    de Souza Viana, Luciano; Scapulatempo Neto, Cristovam; Vicente Serrano, Sérgio

    2016-01-01

    Lung cancer is the leading world cause of cancer-related death, in both genders, and smoking is the main etiological factor. The discovery of immune checkpoints corroborates the hypothesis that ligands presented in tumors modulate the mechanisms of carcinogenesis and the immune activity of tumor microenvironment. Among the most studied coregulatory molecules, PD-1 (programmed cell death 1) and its ligand PD-L1 (programmed cell death 1 ligand 1) are noteworthy. The present study aims to enhance the understanding of the tumor microenvironment of lung cancer patients who underwent surgery, by means of analysis of PD-L1 expression in tumor cells and in intratumoral immune cells (IICs). It was found that PD-L1 expression was more frequent in tumor cells than in IICs. Collective analysis by Tissue Microarray Assay (TMA) for PD-L1 expression in tumor cells and IICs did not reproduce the findings for separate individual analysis of tumor tissues. Patients with past history of smoking were more likely to express PD-L1 in tumor cells than those who never smoked. Patients with past history of smoking were less likely to have PD-L1 positive IICs compared to those who had never smoked. The immunohistochemical expression of PD-L1 in tumor cells and IICs did not correlate with survival. PMID:27747247

  9. Test-retest reliability of UPDRS-III, dyskinesia scales, and timed motor tests in patients with advanced Parkinson's disease: an argument against multiple baseline assessments.

    PubMed

    Metman, Leo Verhagen; Myre, Brian; Verwey, Niek; Hassin-Baer, Sharon; Arzbaecher, Jean; Sierens, Diane; Bakay, Roy

    2004-09-01

    The primary objective of this study was to assess the intra-rater reliability of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III) in patients with advanced Parkinson's disease (PD). The secondary objective was to assess the intra-rater reliability of standard timed motor tests and dyskinesia scales to determine the necessity of multiple baseline core evaluations before surgery for PD. We carried out two standardized preoperative core evaluations of patients with advanced PD scheduled to undergo deep brain stimulation. Patients were examined in the defined off and on conditions by the same rater. UPDRS-III, timed tests, and dyskinesia scores from the two evaluations were compared using Wilcoxon Signed Ranks tests and intraclass correlation coefficients (ICC). Differences in UPDRS-III scores for the two visits were clinically and statistically nonsignificant, and the ICC was 0.9. Similarly, there were no significant differences in timed motor tests or dyskinesia scores, with a median ICC of 0.8. The results indicate that previous findings of high test-retest reliability of UPDRS-III in early untreated PD patients can now be extended to those with advanced disease complicated by motor fluctuations. In addition, test-retest reliability of dyskinesia scales and timed motor tests was high. Taken together, these findings challenge the need for multiple baseline assessments as currently stipulated in core assessment protocols for surgical intervention in PD. PMID:15372601

  10. Effect and safety of duodenal levodopa infusion in advanced Parkinson's disease: a retrospective multicenter outcome assessment in patient routine care.

    PubMed

    Antonini, A; Odin, P; Opiano, L; Tomantschger, V; Pacchetti, C; Pickut, B; Gasser, U E; Calandrella, D; Mancini, F; Zibetti, M; Minafra, B; Bertaina, I; De Deyn, P; Cras, C; Wolf, E; Spielberger, S; Poewe, W

    2013-11-01

    Duodenal levodopa infusion represents an effective strategy to manage motor and non-motor complications in patients with advanced Parkinson's disease (PD). However, most published clinical series regard small numbers of patients and do not exceed 1 year follow-up. In this multi-national observational cohort study conducted in seven specialised PD clinics and university hospitals we assessed long-term safety and outcome of chronic treatment with intra-duodenal levodopa infusions in a large population of patients with advanced PD. The starting population consisted of 98 treated patients (safety population). We report clinical outcomes of 73 patients with subsequent efficacy assessment(s) (efficacy population) over a follow-up period up to 2 years. Follow-up periods and collection of clinical observations varied based on individual routine care program. At last follow-up there was a significant (p ≤ 0.05) reduction in duration of "Off" periods as well as dyskinesia duration and severity that was associated with an improvement of quality of life. Twenty three patients (25.3 % of the safety population) withdraw, due to adverse drug reaction (5), procedure and device related events (7), compliance (3) and lack of efficacy (8). The mean duration for last value reported after baseline (LV) was 608 ± 292 days (median: 697 days). Our results demonstrate significant and sustained benefit over a long observation period in motor complications and in quality of life following a change from oral pulsatile to continuous levodopa delivery. The relatively large number of withdrawals reflects the current use of duodenal levodopa infusion in very advanced PD patients. PMID:23595879

  11. Clinicopathological and prognostic significance of programmed cell death ligand1 (PD-L1) expression in patients with non-small cell lung cancer: a meta-analysis

    PubMed Central

    Pan, Zhen-Kui; Ye, Feng; Wu, Xuan; An, Han-Xiang

    2015-01-01

    Objective Programmed cell death 1 (PD-1) and one of its ligands, PD-L1, are key immune checkpoint proteins. Evidences showed PD-L1 is an emerging biomarker for immunotherapy by anti-PD-1 and anti-PD-L1 antibody in non-small cell lung cancer (NSCLC). To investigate the association of PD-L1 protein expression with clinicopathological features and its impact on survival outcome, we conducted a meta-analysis. Methods A comprehensive literature search of electronic databases (up to July 10, 2014) was performed. Correlation between PD-L1 expression and clinicopathological features and overall survival (OS) was analyzed by synthesizing the qualified data. Publication biases were examined. Results A total of 1,550 NSCLC patients from 9 studies were included. The pooled odds ratios (ORs) indicated high PD-L1 expression was associated with poor tumor differentiation [OR =0.53, 95% confidence interval (CI): 0.39-0.72, P<0.0001]. Whereas, none of other clinicopathological characteristics [gender, smoking status, histological type, invasive depth of tumor, status of lymph node metastasis and tumor node metastasis (TNM) stage] were correlated with PD-L1 expression in current analysis. The combined hazard ratio (HR) for OS showed high expression of PD-L1 impaired the OS in NSCLC (HRpositive/negative =1.47, 95% CI: 1.19-1.83, P=0.0004). Conclusions Our meta-analysis indicated PD-L1 protein expression in NSCLC was not associated with common clinicopathological characteristics, except tumor differentiation. It was a poor prognostic biomarker for NSCLC. Further research should be performed to investigate the precise clinicopathological and prognostic significance of PD-L1 in NSCLC under uniform testing standard. PMID:25922726

  12. T cell Bim levels reflect responses to anti–PD-1 cancer therapy

    PubMed Central

    Dronca, Roxana S.; Liu, Xin; Harrington, Susan M.; Chen, Lingling; Cao, Siyu; Kottschade, Lisa A.; McWilliams, Robert R.; Block, Matthew S.; Nevala, Wendy K.; Thompson, Michael A.; Mansfield, Aaron S.; Park, Sean S.; Markovic, Svetomir N.

    2016-01-01

    Immune checkpoint therapy with PD-1 blockade has emerged as an effective therapy for many advanced cancers; however, only a small fraction of patients achieve durable responses. To date, there is no validated blood-based means of predicting the response to PD-1 blockade. We report that Bim is a downstream signaling molecule of the PD-1 pathway, and its detection in T cells is significantly associated with expression of PD-1 and effector T cell markers. High levels of Bim in circulating tumor-reactive (PD-1+CD11ahiCD8+) T cells were prognostic of poor survival in patients with metastatic melanoma who did not receive anti–PD-1 therapy and were also predictive of clinical benefit in patients with metastatic melanoma who were treated with anti–PD-1 therapy. Moreover, this circulating tumor-reactive T cell population significantly decreased after successful anti–PD-1 therapy. Our study supports a crucial role of Bim in both T cell activation and apoptosis as regulated by PD-1 and PD-L1 interactions in effector CD8+ T cells. Measurement of Bim levels in circulating T cells of patients with cancer may provide a less invasive strategy to predict and monitor responses to anti–PD-1 therapy, although future prospective analyses are needed to validate its utility. PMID:27182556

  13. Patient-specific Monte Carlo dose calculations for 103Pd breast brachytherapy

    NASA Astrophysics Data System (ADS)

    Miksys, N.; Cygler, J. E.; Caudrelier, J. M.; Thomson, R. M.

    2016-04-01

    This work retrospectively investigates patient-specific Monte Carlo (MC) dose calculations for 103Pd permanent implant breast brachytherapy, exploring various necessary assumptions for deriving virtual patient models: post-implant CT image metallic artifact reduction (MAR), tissue assignment schemes (TAS), and elemental tissue compositions. Three MAR methods (thresholding, 3D median filter, virtual sinogram) are applied to CT images; resulting images are compared to each other and to uncorrected images. Virtual patient models are then derived by application of different TAS ranging from TG-186 basic recommendations (mixed adipose and gland tissue at uniform literature-derived density) to detailed schemes (segmented adipose and gland with CT-derived densities). For detailed schemes, alternate mass density segmentation thresholds between adipose and gland are considered. Several literature-derived elemental compositions for adipose, gland and skin are compared. MC models derived from uncorrected CT images can yield large errors in dose calculations especially when used with detailed TAS. Differences in MAR method result in large differences in local doses when variations in CT number cause differences in tissue assignment. Between different MAR models (same TAS), PTV {{D}90} and skin {{D}1~\\text{c{{\\text{m}}3}}} each vary by up to 6%. Basic TAS (mixed adipose/gland tissue) generally yield higher dose metrics than detailed segmented schemes: PTV {{D}90} and skin {{D}1~\\text{c{{\\text{m}}3}}} are higher by up to 13% and 9% respectively. Employing alternate adipose, gland and skin elemental compositions can cause variations in PTV {{D}90} of up to 11% and skin {{D}1~\\text{c{{\\text{m}}3}}} of up to 30%. Overall, AAPM TG-43 overestimates dose to the PTV ({{D}90} on average 10% and up to 27%) and underestimates dose to the skin ({{D}1~\\text{c{{\\text{m}}3}}} on average 29% and up to 48%) compared to the various MC models derived using the post-MAR CT images studied

  14. Facile synthesis of Pt-Pd@Silicon nanostructure as an advanced electrocatalyst for direct methanol fuel cells

    NASA Astrophysics Data System (ADS)

    Ensafi, Ali A.; Jafari-Asl, M.; Rezaei, B.; Abarghoui, M. Mokhtari; Farrokhpour, H.

    2015-05-01

    In this work, platinum-palladium (Pt-Pd) is assembled in-situ on the surface of porous silicon flour (PSiF) through chemical reduction of PtCl62-/PdCl42- and oxidation of the precursor solution SiF64-. The components and the morphological properties of the Pt-Pd on PSiF is investigated by means of transmission electron microscopy, energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction techniques. In the next stage, screen printed graphene electrode (SPGE) is prepared by electro-reduction of exfoliated graphene oxide at the surface of a screen printed carbon electrode (SPCE), which is subsequently characterized by FT-IR, Raman spectroscopy, FE-SEM, and electrochemical methods. Finally, a combination of Pt-Pd@PSi nanostructure and SPGE is used for the electro-oxidation of methanol in direct methanol fuel cell. The electrochemical results demonstrate that the Pt-Pd@PSiF-SPGE exhibits an excellent electrocatalytic activity for methanol oxidation. In addition, the electron transfer kinetic of methanol oxidation on Pt-Pd@PSiF-SPGE is investigated by electrochemical impedance spectroscopy. The results showed that the surface of Pt-Pd@PSiF-SPGE is not affected (poisoned) by intermediate products such as CO.

  15. Pd-on-Au Supra-nanostructures Decorated Graphene Oxide: An Advanced Electrocatalyst for Fuel Cell Application.

    PubMed

    Tao, Yingzhou; Dandapat, Anirban; Chen, Liming; Huang, Youju; Sasson, Yoel; Lin, Zhenyu; Zhang, Jiawei; Guo, Longhua; Chen, Tao

    2016-08-30

    We report a very easy and effective approach for synthesizing unique palladium-on-gold supra-nanostructure (Au@Pd-SprNS)-decorated graphene oxide (GO) nanosheets. The SprNSs comprising Au nanorods as core and a unique close-packed assembly of tiny anisotropic Pd nanoparticles (NPs) as shell were homogeneously distributed on the GO surface via electrostatic self-assembly. Compared with the traditional one-pot method for synthesis of metal NPs on GO sheets, the size and shape of core-shell Au@Pd SprNSs can be finely controlled and uniformly distributed on the GO carrier. Interestingly, this Au@Pd-SprNSs/GO nanocomposite displayed high electrocatalytic activities toward the oxidation of methanol, ethanol, and formic acid, which can be attributed to the abundance of intrinsic active sites including high density of atomic steps, ledges and kinks, Au-Pd heterojunctions and cooperative action of the two metals of the SprNSs. Additionally, uniform dispersion of the SprNSs over the GO nanosheets prevent agglomeration between the SprNSs, which is of great significance to enhance the long-term stability of catalyst. This work will introduce a highly efficient Pd-based nanoelectrocatalyst to be used in fuel cell application. PMID:27482606

  16. Delirium in patients with advanced cancer.

    PubMed

    Lawlor, Peter G; Bruera, Eduardo D

    2002-06-01

    Managing delirium is of major importance in end-of-life care and frequently gives rise to controversies and to clinical and ethical dilemmas. These problems arise from a number of causes, including the sometimes-poor recognition or misdiagnosis of delirium despite its frequent occurrence. Delirium generates major symptomatic of distress for the patient, consequent stress for the patient's family, the potential to misinterpret delirium symptomatology, and behavioral management challenges for health care professionals. Paradoxically, delirium is potentially reversible in some episodes, but in many patients delirium presents a nonreversible terminal episode. Greater educational efforts are required to improve the recognition of delirium and lead to a better understanding of its impact in end-of-life care. Future research might focus on phenomenology, the development of low-burden instruments for assessment, communication strategies, and the family education regarding the manifestations of delirium. Further research is needed among patients with advanced cancer to establish a predictive model for reversibility that recognizes both baseline vulnerability factors and superimposed precipitating factors. Evidence-based guidelines should be developed to assist physicians in more appropriate use of sedation in the symptomatic management of delirium.

  17. PD trivia: Making learning fun.

    PubMed

    Kennedy, Liana

    2006-01-01

    Nurses are educators. It is the aim of every educator that his or her teaching should translate into learning. Effective teaching is especially of importance in assuring that patients learn to perform their own peritoneal dialysis (PD). In facilitating an environment where learning can occur, making learning fun is the objective. It is with this mandate that PD Trivia was created. PD Trivia is an interactive game created to facilitate and reinforce learning. PD Trivia consists of 100 essential questions to making PD a success at home. Evaluations at the peritoneal dialysis clinic have revealed excellent quantitative and qualitative results of this simple but comprehensive teaching tool for effective learning of PD.

  18. An Increase of Plasma Advanced Oxidation Protein Products Levels Is Associated with Cardiovascular Risk in Incident Peritoneal Dialysis Patients: A Pilot Study

    PubMed Central

    Gonzalez, Elena; Bajo, Maria-Auxiliadora; Carrero, Juan J.; Lindholm, Bengt; Grande, Cristina; Sánchez-Villanueva, Rafael; Del Peso, Gloria; Díaz-Almirón, Mariana; Iglesias, Pedro; Díez, Juan J.; Selgas, Rafael

    2015-01-01

    Advanced oxidation protein products (AOPPs) are considered as markers and even mediators of the proinflammatory effect of oxidative stress in uremia. We hypothesized that an increase of oxidative stress associated with peritoneal dialysis (PD), estimated by the variation of plasma AOPPs over time, might be associated with cardiovascular (CV) risk and overall prognosis. In 48 PD patients, blood samples were collected on two occasions: the first one in the first six months after starting PD therapy and the second one, one year after. The plasma AOPPs level variation over the first year on PD was significantly associated with CV antecedents and also with CV prognosis. In those patients in whom the AOPPs levels increased more than 50% above the baseline value, a significant association with past and future CV disease was confirmed. These patients had 4.7 times greater risk of suffering later CV disease than those with a smaller increase, even after adjusting for previous CV history. Our data suggest that the increase of AOPPs plasma level over the first year on PD is conditioned by CV antecedents but also independently predicts CV prognosis. AOPPs plasma levels seem to represent the CV status of PD patients with sufficient sensitivity to identify those with a clearly sustained higher CV risk. PMID:26581178

  19. Dietary intake of advanced cancer patients.

    PubMed

    Walsh, T D; Bowman, K B; Jackson, G P

    1983-02-01

    A state registered dietitian assessed the voluntary dietary intake of 13 advanced cancer inpatients on one ward of St. Christopher's Hospice for five consecutive days. There were 11 females, two males; median age 74 years (range 56 to 83). Two patients died on the fourth day of the study. A partially individualised weighed technique was used. Standard sized scoops and spoons were used to serve the food in small, medium or large standard portions (depending on appetite) and were weighed as served. Individual plate waste (by weight) was subtracted to give estimated individual intake. Foods provided by visitors was not included. The median and range of individual mean daily intakes (estimated) were: energy 5760 (938-8945) kJ, 1376 (224-2137) kcal; protein 44 (11-86) g; fat 52 (9-93) g; carbohydrate 169 (21-194) g; calcium 748 (268-1457) mg; iron 4.8 (0.5-21.0) mg; dietary fibre 5.0 (0.5-21.0) g. Compared to recommended amounts, energy, iron and dietary fibre intakes were low; calcium intake was high. Nutritional status may affect prognosis and/or subjective well-being in advanced cancer. The value of nutritional supplementation and the role of appetite stimulants in improving nutritional status needs investigation.

  20. Dietary intake of advanced cancer patients.

    PubMed

    Walsh, T D; Bowman, K B; Jackson, G P

    1983-02-01

    A state registered dietitian assessed the voluntary dietary intake of 13 advanced cancer inpatients on one ward of St. Christopher's Hospice for five consecutive days. There were 11 females, two males; median age 74 years (range 56 to 83). Two patients died on the fourth day of the study. A partially individualised weighed technique was used. Standard sized scoops and spoons were used to serve the food in small, medium or large standard portions (depending on appetite) and were weighed as served. Individual plate waste (by weight) was subtracted to give estimated individual intake. Foods provided by visitors was not included. The median and range of individual mean daily intakes (estimated) were: energy 5760 (938-8945) kJ, 1376 (224-2137) kcal; protein 44 (11-86) g; fat 52 (9-93) g; carbohydrate 169 (21-194) g; calcium 748 (268-1457) mg; iron 4.8 (0.5-21.0) mg; dietary fibre 5.0 (0.5-21.0) g. Compared to recommended amounts, energy, iron and dietary fibre intakes were low; calcium intake was high. Nutritional status may affect prognosis and/or subjective well-being in advanced cancer. The value of nutritional supplementation and the role of appetite stimulants in improving nutritional status needs investigation. PMID:6841131

  1. Baseline hydration status in incident peritoneal dialysis patients: the initiative of patient outcomes in dialysis (IPOD-PD study)†

    PubMed Central

    Ronco, Claudio; Verger, Christian; Crepaldi, Carlo; Pham, Jenny; De los Ríos, Tatiana; Gauly, Adelheid; Wabel, Peter; Van Biesen, Wim

    2015-01-01

    Background Non-euvolaemia in peritoneal dialysis (PD) patients is associated with elevated mortality risk. There is an urgent need to collect data to help us understand the association between clinical practices and hydration and nutritional status, and their effects on patient outcome. Methods The aim of this prospective international, longitudinal observational cohort study is to follow up the hydration and nutritional status, as measured by bioimpedance spectroscopy using the body composition monitor (BCM) of incident PD patients for up to 5 years. Measures of hydration and nutritional status and of clinical, biochemical and therapy-related data are collected directly before start of PD treatment, at 1 and 3 months, and then every 3 months. This paper presents the protocol and a pre-specified analysis of baseline data of the cohort. Results A total of 1092 patients (58.1% male, 58.0 ± 15.3 years) from 135 centres in 32 countries were included. Median fluid overload (FO) was 2.0 L (males) and 0.9 L (females). Less than half of the patients were normohydrated (38.7%), whereas FO > 1.1 L was seen in 56.5%. Systolic and diastolic blood pressure were 139.5 ± 21.8 and 80.0 ± 12.8 mmHg, respectively, and 25.1% of patients had congestive heart failure [New York Heart Association (NYHA) 1 or higher]. A substantial number of patients judged to be not overhydrated on clinical judgement appeared to be overhydrated by BCM measurement. Overhydration at baseline was independently associated with male gender and diabetic status. Conclusions The majority of patients starting on PD are overhydrated already at start of PD. This may have important consequences on clinical outcomes and preservation of residual renal function. Substantial reclassification of hydration status by BCM versus on a clinical basis was necessary, especially in patients who were not overtly overhydrated. Both clinical appreciation and bioimpedance should be combined in clinical decision-making on

  2. PD-1 and PD-L1 inhibitors in melanoma treatment: past success, present application and future challenges.

    PubMed

    Lee, Jenny; Kefford, Richard; Carlino, Matteo

    2016-06-01

    Anti-programmed death (PD)-1 antibodies have now become the standard of care for advanced melanoma, with two drugs gaining US FDA approval in recent years: nivolumab and pembrolizumab. Both have demonstrated significant activity and durable response with a manageable toxicity profile. Despite initial success, ongoing challenges include patient selection and predictors of response, innate resistance and optimizing combination strategies. In this overview, we take a closer look at the history and development of therapeutic targets to the PD-1/PD-ligand (L)1 pathway, clinical evidence, availability of biomarkers and their limitations in clinical practice and future strategies to improve treatment outcomes. PMID:27197541

  3. Dramatic response to anti-PD-1 therapy in a patient of squamous cell carcinoma of thymus with multiple lung metastases.

    PubMed

    Yang, Yan; Ding, Liren; Wang, Pingli

    2016-07-01

    Immunotherapy directed at the programmed cell death-1 receptor (PD-1) or its ligand PD-L1 has demonstrated efficacy in some malignancies, such as metastatic melanoma and non-small-cell lung cancer (NSCLC). Compared with cytotoxic chemotherapy, radiotherapy or molecular targeted agent, it is an innovative way to treat malignancies with durable clinical responses and manageable adverse. We present a case of female patient with squamous cell carcinoma of thymus involving multiple lung metastases, who was successfully treated with anti-PD-1 monoclonal antibody, pembrolizumab. PMID:27499991

  4. Bevacizumab improves survival for patients with advanced cervical cancer

    Cancer.gov

    Patients with advanced, recurrent, or persistent cervical cancer that was not curable with standard treatment who received the drug bevacizumab (Avastin) lived 3.7 months longer than patients who did not receive the drug, according to an interim analysis

  5. Genetic polymorphisms of immune checkpoint proteins PD-1 and TIM-3 are associated with survival of patients with hepatitis B virus-related hepatocellular carcinoma

    PubMed Central

    Li, Zhu; Li, Na; Li, Fang; Zhou, Zhihua; Sang, Jiao; Jin, Zhao; Liu, Huihui; Han, Qunying; Lv, Yi; Liu, Zhengwen

    2016-01-01

    Programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain containing molecule 3 (TIM-3) are involved in hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study examined the associations of PD1 and TIM3 polymorphisms with the overall survival (OS) of a prospective cohort of 258 HBV-related HCC patients. Results showed that PD1 +8669 G allele-containing genotypes or TIM3 −1516 genotype GG were significantly associated with longer OS (P < 0.001 and P = 0.001, respectively). In multivariate analysis, PD1 +8669 G allele-containing genotypes and TIM3 −1516 genotype GG were independently associated with longer OS (hazard ratio (HR), 1.835; 95% confidence interval (CI), 1.342–2.509; P < 0.001 and HR, 2.070; 95%CI, 1.428–3.002; P < 0.001, respectively). PD1 +8669 G allele-containing genotypes were significantly associated with longer OS in patients receiving surgical (resection or radiofrequency) treatment, transcatheter arterial chemoembolization (TACE) or supportive and symptomatic treatment. TIM3 −1516 genotype GG was significantly associated with longer OS in TACE patients. In multivariate analysis, PD1 +8669 G allele-containing genotypes were independently associated with longer OS in each treatment population. TIM3 −1516 genotype GG was independently associated with longer OS in patients receiving surgical treatment or TACE. These findings suggest that PD1 +8669 A/G and TIM3 −1516 G/T polymorphisms may affect the prognosis of HBV-related HCC and may be new predictors of prognosis for HCC patients. PMID:27034168

  6. Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma.

    PubMed

    Leonard, John P; LaCasce, Ann S; Smith, Mitchell R; Noy, Ariela; Chirieac, Lucian R; Rodig, Scott J; Yu, Jian Q; Vallabhajosula, Shankar; Schoder, Heiko; English, Patricia; Neuberg, Donna S; Martin, Peter; Millenson, Michael M; Ely, Scott A; Courtney, Rachel; Shaik, Naveed; Wilner, Keith D; Randolph, Sophia; Van den Abbeele, Annick D; Chen-Kiang, Selina Y; Yap, Jeffrey T; Shapiro, Geoffrey I

    2012-05-17

    Mantle cell lymphoma (MCL) carries an unfavorable prognosis and requires new treatment strategies. The associated t(11:14) translocation results in enhanced cyclin D1 expression and cyclin D1-dependent kinase activity to promote cell-cycle progression. A pharmacodynamic study of the selective CDK4/6 inhibitor PD0332991 was conducted in 17 patients with relapsed disease, using 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) and 3-deoxy-3[(18)F]fluorothymidine (FLT) positron emission tomography (PET) to study tumor metabolism and proliferation, respectively, in concert with pre- and on-treatment lymph node biopsies to assess retinoblastoma protein (Rb) phosphorylation and markers of proliferation and apoptosis. Substantial reductions in the summed FLT-PET maximal standard uptake value (SUV(max)), as well as in Rb phosphorylation and Ki-67 expression, occurred after 3 weeks in most patients, with significant correlations among these end points. Five patients achieved progression-free survival time of > 1 year (range, 14.9-30.1+ months), with 1 complete and 2 partial responses (18% objective response rate; 90% confidence interval, 5%-40%). These patients demonstrated > 70%, > 90%, and ≥ 87.5% reductions in summed FLT SUV(max) and expression of phospho-Rb and Ki67, respectively, parameters necessary but not sufficient for long-term disease control. The results of the present study confirm CDK4/6 inhibition by PD0332991 at a well-tolerated dose and schedule and suggest clinical benefit in a subset of MCL patients. This study is registered at www.clinicaltrials.gov under identifier NCT00420056.

  7. Evolving Approaches to Patients with Advanced Differentiated Thyroid Cancer

    PubMed Central

    Sherman, Steven I.

    2013-01-01

    Advanced differentiated thyroid cancer (DTC), defined by clinical characteristics including gross extrathyroidal invasion, distant metastases, radioiodine (RAI) resistance, and avidity for 18-fluorodeoxyglucose (positron emission tomography-positive), is found in approximately 10–20% of patients with DTC. Standard therapy (surgery, RAI, TSH suppression with levothyroxine) is ineffective for many of these patients, as is standard chemotherapy. Our understanding of the molecular mechanisms leading to DTC and the transformation to advanced DTC has rapidly evolved over the past 15–20 years. Newer targeted therapy, specifically inhibitors of intracellular kinase signaling pathways, and cooperative multicenter clinical trials have dramatically changed the therapeutic landscape for patients with advanced DTC. In this review focusing on morbidities, molecules, and medicinals, we present a patient with advanced DTC, explore the genetics and molecular biology of advanced DTC, and review evolving therapies for these patients including multikinase inhibitors, selective kinase inhibitors, and combination therapies. PMID:23575762

  8. Fungal peritonitis in patients undergoing peritoneal dialysis (PD) in Brazil: molecular identification, biofilm production and antifungal susceptibility of the agents.

    PubMed

    Giacobino, Juliana; Montelli, Augusto Cezar; Barretti, Pasqual; Bruder-Nascimento, Ariane; Caramori, Jacqueline Teixeira; Barbosa, Luciano; Bagagli, Eduardo

    2016-10-01

    This paper presents data on fungal peritonitis (FP) in patients undergoing peritoneal dialysis (PD) at the University Hospital of Botucatu Medical School, São Paulo, Brazil. In a total of 422 patients, 30 developed FP, from which the medical records and the fungal isolates of 23 patient cases were studied. All patients presented abdominal pain, cloudy peritoneal effluent, needed hospitalization, had the catheter removed and were treated with fluconazole or fluconazole plus 5-flucitosine; six of them died due to FP. Concerning the agents, it was observed that Candida parapsilosis was the leading species (9/23), followed by Candida albicans (5/23), Candida orthopsilosis (4/23), Candida tropicalis (3/23), Candida guilliermondii (1/23), and Kodamaea ohmeri (1/23). All the isolates were susceptible to amphotericin B, voriconazole and caspofungin whereas C. albicans isolates were susceptible to all antifungals tested. Resistance to fluconazole was observed in three isolates of C. orthopsilosis, and dose-dependent susceptibility to this antifungal was observed in two isolates of C. parapsilosis and in the K. ohmeri isolate. Biofilm production estimates were high or moderate in most isolates, especially in C. albicans species, and low in C. parapsilosis species, with a marked variation among the isolates. This Brazilian study reinforces that FP in PD is caused by a diverse group of yeasts, most prevalently C. parapsilosis sensu stricto species. In addition, they present significant variation in susceptibility to antifungals and biofilm production, thus contributing to the complexity and severity of the clinical features.

  9. A Radiation Badge Survey for Family Members Living With Patients Treated With a {sup 103}Pd Permanent Breast Seed Implant

    SciTech Connect

    Keller, Brian M. Pignol, Jean-Philippe; Rakovitch, Eileen; Sankreacha, Raxa; O'Brien, Peter

    2008-01-01

    Purpose: Sixty-seven patients with early-stage breast cancer were treated in a Phase I/II clinical trial using a {sup 103}Pd permanent breast seed implant as adjuvant radiotherapy after breast-conserving surgery. We report the dose received by family members living with these patients and compare measured doses with theoretical worst-case scenario estimates. Methods and Materials: Exposure-rate measurements were taken at 1 m from the patient by using a calibrated low-energy survey meter. Landauer (Landauer Inc., Glenwood, IL) Luxel badges, with sensitivity of 0.01 mSv, were given to family members to wear after the implantation. Badge readings for 33 spouses and 28 other family members were used to estimate effective doses, and these were compared with theory. Results: Average preimplantation planning target volume from computed tomography was 50.3 ml (range, 18.0-96.7 ml), and average preimplantation distance between the skin and the most anterior planning target volume margin was 0.57 cm. The average maximum exposure rate was measured to be 2.4 {+-} 1.1 mR/h, and average measured dose to a spouse was 0.99 {+-} 1.0 mSv. The calculated exposure rates and spousal doses using preimplantation computed tomography scan data overestimated those measured. Average measured family member dose (excluding spouses) was 0.20 {+-} 0.58 mSv. Conclusions: Based on measured and calculated spousal doses, a permanent breast seed implant using {sup 103}Pd is safe for the public. However, it is recommended that extra precautions in the way of a breast patch be used when patients with an implant will be in the vicinity of toddlers or pregnant women.

  10. The promise of PD-1 inhibitors in gastro-esophageal cancers: microsatellite instability vs. PD-L1

    PubMed Central

    Jin, Zhaohui

    2016-01-01

    Preliminary clinical studies of anti-programmed cell death-1 (anti-PD-1) therapy in gastro-esophageal cancers have suggested promising single-agent activity. In patients who received prior treatment for advanced disease, pembrolizumab has been associated with a response rate of 20% in programmed cell death-1 ligand 1 (PD-L1)-positive tumors, and nivolumab with a response rate of 12% in unselected tumors. Both agents yielded a median duration of response lasting ~6–7 months. PD-L1 expression and microsatellite instability (MSI) have emerged as potential predictive markers for PD-1/PD-L1 blockade. PD-L1 expression in tumor cells and in immune cells within the tumor microenvironment has been detected in 14–24% and ~35% of patients with gastro-esophageal cancer, respectively. PD-L1 tumor cell expression appears to be more common in Epstein-Barr virus (EBV)-positive gastric cancers (GCs) and has been associated with an increased density of tumor-infiltrating lymphocytes (TIL). To date, data are too sparse to determine whether PD-L1 expression predicts efficacy of anti-PD-1 therapy in gastro-esophageal cancer, but data from other tumor types have not been consistent regarding its predictive value. MSI occurs in 10–20% of gastro-esophageal cancers and arises from deficient mismatch repair (MMR). MSI is highly correlated with non-synonymous mutation burden, as well as a dense accumulation of TILs. MSI has been associated with improved response to anti-PD-1 therapy in gastrointestinal cancers. Multiple studies are ongoing which examine therapeutic blockade of the PD-1/PD-L1 axis in unselected patients with gastro-esophageal cancer, as well as patients whose tumors express PD-L1 or exhibit MSI. These studies will clarify their activity in this disease and potentially can determine whether identify a strong predictive biomarker can be identified. Checkpoint inhibition is also being studied in combination with curative-intent chemo (radio) therapy and surgery. PMID

  11. Fewer Advanced Alzheimer's Patients on Feeding Tubes

    MedlinePlus

    ... at someone in the advanced stages of a terminal illness, a feeding tube doesn't make a ... of palliative care (keeping a person with a terminal illness as comfortable as possible), Mitchell said. As ...

  12. Aberrant PD-L1 expression through 3'-UTR disruption in multiple cancers.

    PubMed

    Kataoka, Keisuke; Shiraishi, Yuichi; Takeda, Yohei; Sakata, Seiji; Matsumoto, Misako; Nagano, Seiji; Maeda, Takuya; Nagata, Yasunobu; Kitanaka, Akira; Mizuno, Seiya; Tanaka, Hiroko; Chiba, Kenichi; Ito, Satoshi; Watatani, Yosaku; Kakiuchi, Nobuyuki; Suzuki, Hiromichi; Yoshizato, Tetsuichi; Yoshida, Kenichi; Sanada, Masashi; Itonaga, Hidehiro; Imaizumi, Yoshitaka; Totoki, Yasushi; Munakata, Wataru; Nakamura, Hiromi; Hama, Natsuko; Shide, Kotaro; Kubuki, Yoko; Hidaka, Tomonori; Kameda, Takuro; Masuda, Kyoko; Minato, Nagahiro; Kashiwase, Koichi; Izutsu, Koji; Takaori-Kondo, Akifumi; Miyazaki, Yasushi; Takahashi, Satoru; Shibata, Tatsuhiro; Kawamoto, Hiroshi; Akatsuka, Yoshiki; Shimoda, Kazuya; Takeuchi, Kengo; Seya, Tsukasa; Miyano, Satoru; Ogawa, Seishi

    2016-06-16

    Successful treatment of many patients with advanced cancer using antibodies against programmed cell death 1 (PD-1; also known as PDCD1) and its ligand (PD-L1; also known as CD274) has highlighted the critical importance of PD-1/PD-L1-mediated immune escape in cancer development. However, the genetic basis for the immune escape has not been fully elucidated, with the exception of elevated PD-L1 expression by gene amplification and utilization of an ectopic promoter by translocation, as reported in Hodgkin and other B-cell lymphomas, as well as stomach adenocarcinoma. Here we show a unique genetic mechanism of immune escape caused by structural variations (SVs) commonly disrupting the 3' region of the PD-L1 gene. Widely affecting multiple common human cancer types, including adult T-cell leukaemia/lymphoma (27%), diffuse large B-cell lymphoma (8%), and stomach adenocarcinoma (2%), these SVs invariably lead to a marked elevation of aberrant PD-L1 transcripts that are stabilized by truncation of the 3'-untranslated region (UTR). Disruption of the Pd-l1 3'-UTR in mice enables immune evasion of EG7-OVA tumour cells with elevated Pd-l1 expression in vivo, which is effectively inhibited by Pd-1/Pd-l1 blockade, supporting the role of relevant SVs in clonal selection through immune evasion. Our findings not only unmask a novel regulatory mechanism of PD-L1 expression, but also suggest that PD-L1 3'-UTR disruption could serve as a genetic marker to identify cancers that actively evade anti-tumour immunity through PD-L1 overexpression. PMID:27281199

  13. PD-1 blockade therapy in renal cell carcinoma: current studies and future promises.

    PubMed

    Massari, F; Santoni, M; Ciccarese, C; Santini, D; Alfieri, S; Martignoni, G; Brunelli, M; Piva, F; Berardi, R; Montironi, R; Porta, C; Cascinu, S; Tortora, G

    2015-02-01

    RCC is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Evasion of immune surveillance, a process defined immune-editing, leads to malignant progression. The striking improvement of knowledge in immunology has led to the identification of immune checkpoints (such as CTLA-4 and PD-1), whose blockage enhances the antitumor immunity. The interaction between PD-1, an inducible inhibitory receptor expressed on lymphocytes and DCs, and PD-L1 ligand, expressed by tumor cells, results in a down-regulation of the T-cell response. Therefore, the PD-1/PD-L1 axis inhibition by targeted-antibodies, increasing the T-cell proliferation and cytotoxicity, represents a promising mechanism to stimulate the anti-tumor activity of the immune system, improving the outcomes of cancer patients. Several PD-1 and PD-L1 inhibitors have been evaluated in different tumor types, showing promising results. The interesting correlation between lymphocytes PD-1 expression and RCC advanced stage, grade and prognosis, as well as the selective PD-L1 expression by RCC tumor cells and its potential association with worse clinical outcomes, have led to the development of new anti PD-1/PD-L1 agents, alone or in combination with anti-angiogenic drugs or other immunotherapeutic approaches, for the treatment of RCC. In this review we discuss the role of PD-1/PD-L1 in RCC, focusing on the biological rationale, current clinical studies and promising therapeutic perspectives to target the PD-1 pathway.

  14. The role of antagonists of the PD-1:PD-L1/PD-L2 axis in head and neck cancer treatment.

    PubMed

    Pai, Sara I; Zandberg, Dan P; Strome, Scott E

    2016-10-01

    We review the current clinical knowledge surrounding one of the most promising immune checkpoint pathways currently investigated in head and neck squamous cell carcinoma patients, programmed cell death-1 (PD-1) and its ligands (PD-L1 and PD-L2). We review ongoing clinical trials and associated clinical responses observed with targeting the receptor, PD-1, and its ligand, PD-L1. A recent phase III clinical trial (Checkmate 141) demonstrated an improved overall survival in head and neck cancer patients treated with anti-PD-1 monotherapy as compared to standard of care for recurrent and/or metastatic disease, which raises questions on how best to incorporate immunotherapy in the context of standard of care. We discuss biomarkers of response to this class of novel drugs, which is an area of active investigation. Lastly, we project future directions in the field wherein understanding how the Fc portions of the various monoclonal antibodies may impact their clinical efficacy as well as discuss areas where our next advances may take place, such as combination strategies.

  15. Registration of PD 05064, PD 05069, PD 05070, and PD 05071 germplasm lines of cotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    PD 05064, PD 05069, PD 05070, and PD 05071 are noncommercial breeding lines of cotton jointly released by the Agricultural Research Service, United States Department of Agriculture, the Clemson University Experiment Station, and Cotton Incorporated in 2014. PD 05064, PD 05069, PD 05070, and PD 05071...

  16. Preexisting Levels of CD4 T Cells Expressing PD-1 Are Related to Overall Survival in Prostate Cancer Patients Treated with Ipilimumab.

    PubMed

    Kwek, Serena S; Lewis, Jera; Zhang, Li; Weinberg, Vivian; Greaney, Samantha K; Harzstark, Andrea L; Lin, Amy M; Ryan, Charles J; Small, Eric J; Fong, Lawrence

    2015-09-01

    Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) blockade can induce tumor regression and improved survival in cancer patients. This treatment can enhance adaptive immune responses without an exogenous vaccine, but the immunologic biomarkers associated with improved clinical outcome in cancer patients are not fully established. A phase Ib trial in patients with metastatic, castration-resistant prostate cancer was performed combining ipilimumab with sargramostim (GM-CSF). In addition to evaluating ipilimumab dose, patients were followed clinically for response and overall survival, and for immunomodulation of circulating T cells. PSA declines of ≥50% and radiographic responses were observed at doses of ≥3 mg/kg/dose. Timing of clinical responses could be either immediate or delayed. Durable responses were also observed off treatment. A subset of patients experienced long-term survival with or without objective clinical responses. The relationship between T-cell phenotype in peripheral blood and overall survival was examined retrospectively. We found that the treatment induced an increase in the levels of CD4(+) effector T (Teff) cells, regulatory T cells, PD-1(+) CD4 Teff cells, and PD-1(+) CD8 T cells. However, these increased levels were not associated with overall survival. Instead, low pretreatment baseline levels of PD-1(+) CD4 Teff cells were found to correlate with longer overall survival. Furthermore, baseline levels of PD-1(+) CD4 Teff cells from patients with shorter overall survival were higher than from cancer-free male control subjects. These results suggest that preexisting expression of immunologic checkpoint marker PD-1 on CD4 Teff cells may help identify patients that may benefit from ipilimumab treatment. PMID:25968455

  17. An Evaluation of the Impact of PD-1 Pathway Blockade on Reproductive Safety of Therapeutic PD-1 Inhibitors.

    PubMed

    Poulet, Frederique M; Wolf, Jayanthi J; Herzyk, Danuta J; DeGeorge, Joseph J

    2016-04-01

    This report discusses the principles of reproductive toxicity risk assessment for biopharmaceuticals blocking the PD-1/programmed cell death ligand 1 (PD-L1) pathway, which have been developed for the treatment of patients with advanced malignancies. The PD-1/PD-L1 pathway is a T-cell co-inhibitory pathway that normally maintains immune tolerance to self. Its role in pregnancy is to maintain immune tolerance to the fetal allograft. In cancer patients, this signaling pathway is hijacked by some neoplasms to avoid immune destruction. PD-1/PD-L1-blocking agents enhance functional activity of the target lymphocytes to eventually cause immune rejection of the tumor. A therapeutic blockade of PD-1/PD-L1 pathway that occurs at full target engagement provides a unique challenge to address the risk to pregnancy because disruption of the same pathway may also reduce or abrogate maternal immune tolerance to the fetal alloantigens inherited through the father. Typically, nonclinical reproductive and developmental toxicity (DART) studies in animals (rats and rabbits) with clinical drug candidates are conducted to identify potential risk in humans and to determine exposure margin for the effects on reproduction as part of the risk assessment. However, for biopharmaceuticals for which the desired mechanism of action cannot be separated from potential deleterious effects to the fetus and when the only relevant toxicology species is nonhuman primate (NHP), the risk to reproduction can be predicted by a mechanism-based assessment using data generated from murine surrogate models as supportive information without conducting DART in NHPs. Such an approach has been used in the evaluation of pregnancy risk of anti-PD-1 agent, pembrolizumab, and has been demonstrated as an important alternative to performing DART studies in NHPs. PMID:27062127

  18. Adaptation of the Fresenius PD+ Cycler for a hearing-impaired patient.

    PubMed

    Kushner, A

    2000-01-01

    Continuous cycling peritoneal dialysis (CCPD) uses a cycler to perform dialysis exchanges and requires the patient to respond to an audible alarm signifying an interruption in the therapy. Consequently, an unassisted hearing-impaired patient could not use the system. By converting the standard alarm to a vibrating signal, the cycler was successfully adapted to accommodate the special needs of our hearing-impaired patient. The items required for the modification were the Sonic Alert Wake Up Alarm (Model SA-WA300: Sonic Alert, Troy, MI, U.S.A.) and the Sonic Alert Super Shaker Bed Vibrator (Model SA-SS120V: Sonic Alert). The patient can place the vibrator under either the pillow or the mattress. When the cycler alarm is activated, vibration wakens the patient. The equipment was purchased from Harris Communications (Eden Prairie, MN, U.S.A.) through a referral by the Easter Seal Society. Three days were needed to complete training compared to an average of one or two days for patients previously trained for continuous ambulatory peritoneal dialysis (CAPD). The patient remained on cycler therapy for approximately four months when the unrelated development of an abdominal hernia required termination of peritoneal dialysis and subsequent transfer to hemodialysis. In conclusion, a modified cycler can provide a safe and efficient renal replacement therapy option for a hearing-impaired patient.

  19. ICOS, SLAM and PD-1 expression and regulation on T lymphocytes reflect the immune dysregulation in patients with HIV-related illness with pulmonary tuberculosis

    PubMed Central

    Jurado, Javier Oscar; Pasquinelli, Virginia; Alvarez, Ivana Belén; Martínez, Gustavo Javier; Laufer, Natalia; Sued, Omar; Cahn, Pedro; Musella, Rosa María; Abbate, Eduardo; Salomón, Horacio; Quiroga, María Florencia

    2012-01-01

    Background Tuberculosis (TB) continues to be the most frequent cause of illness and death from an infectious agent globally, and its interaction with HIV is having devastating effects. To investigate how HIV alters the immune response to Mycobacterium tuberculosis (Mtb), we assessed basal and Mtb-induced proliferation, cytokine production, and expression of signalling lymphocytic activation molecule (SLAM), inducible costimulator (ICOS) and programmed death-1 (PD-1) on T lymphocytes from HIV-positive individuals coinfected with TB, HIV-positive subjects, TB patients and healthy donors (HD). Findings HIV-TB patients showed increased ICOS, SLAM and PD-1 basal levels on T lymphocytes, whereas HIV-positive individuals displayed elevated levels of SLAM and PD-1, TB patients high levels of SLAM, and HD low levels of the three proteins. Mtb-stimulation enhanced ICOS expression in the four groups, but only TB and HD increased SLAM and PD-1 levels. Conclusions These data show the immune deregulation that takes place during the immune response against TB in different study populations. PMID:22713261

  20. Sorafenib in advanced, heavily pretreated patients with soft tissue sarcomas.

    PubMed

    Brämswig, Kira; Ploner, Ferdinand; Martel, Alexandra; Bauernhofer, Thomas; Hilbe, Wolfgang; Kühr, Thomas; Leitgeb, Clemens; Mlineritsch, Brigitte; Petzer, Andreas; Seebacher, Veronika; Stöger, Herbert; Girschikofsky, Michael; Hochreiner, Gerhard; Ressler, Sigrun; Romeder, Franz; Wöll, Ewald; Brodowicz, Thomas

    2014-08-01

    Therapeutic options for patients with advanced pretreated soft tissue sarcomas are limited. However, in this setting, sorafenib has shown promising results. We reviewed the data of 33 patients with soft tissue sarcoma treated with sorafenib within a named patient program in Austria. Twelve physicians from eight different hospitals provided records for the analysis of data. Among the 33 patients, the predominant histological subtype of sarcoma was leiomyosarcoma (n=18, 55%). Other subtypes were represented by only one or two cases. Fifteen patients presented with metastases at the time of diagnosis. Another 17 patients developed metastases later in the course of the disease (data on one patient are missing). Most of the 33 patients had undergone resection of the primary (n=29, 88%) and half of the patients had received radiotherapy (n=17, 52%). Chemotherapy for metastatic disease had been administered to 30 patients (91%). The majority had received two or more regimens of chemotherapy (n=25, 76%) before sorafenib treatment. The use of sorafenib resulted in a median time to treatment failure of 92 days in patients with leiomyosarcoma and 45 days in patients with other histological subtypes. One-third of the patients derived benefits from treatment: four patients were documented with partial response and six with stabilized disease. In terms of treatment-related toxicity, skin problems of various degrees and gastrointestinal disturbances were frequently reported. In this retrospective analysis of heavily pretreated patients with advanced soft tissue sarcomas, sorafenib was associated with some antitumor activity and an acceptable toxicity profile. PMID:24667659

  1. Advanced nurse-patient communication system.

    PubMed

    Unluturk, Mehmet S

    2012-08-01

    Effective communication is the most important part of any healthcare organization. For many years, hospital nurse call solutions had been stand-alone systems with occasional integration to pocket paging for outputting patient call alerts to mobile staff. In the late 1990's, technology enabled in-building wireless phones to supplement or replace paging systems as a means of not only sending alerts, but also enabling voice communication between mobile staff and patients. Today's nurse call market requires integration of additional information from location and ADT (admit, discharge, transfer) systems into what have traditionally been nurse call applications. This system information is required not only at the nursing station, pagers, and phones, but also at PC's placed on each patient care floor in hallways, nurse stations, and offices, and at areas away from the patients, including administrator and clinical engineering offices. It is crucial that nurses have the latest patient information in their hand wherever they go in the hospital. In this paper, MatchMaker.NET has been developed to integrate all these technologies into the hospital's LAN to improve nurse-patient communication. PMID:21541690

  2. Immunotherapy: Beyond Anti-PD-1 and Anti-PD-L1 Therapies.

    PubMed

    Antonia, Scott J; Vansteenkiste, Johan F; Moon, Edmund

    2016-01-01

    Advanced-stage non-small cell lung cancer (NSCLC) and small cell lung cancer are cancers in which chemotherapy produces a survival benefit, although it is small. We now know that anti-PD-1/PD-L1 has substantial clinical activity in both of these diseases, with an overall response rate (ORR) of 15%-20%. These responses are frequently rapid and durable, increase median overall survival (OS) compared with chemotherapy, and produce long-term survivors. Despite these very significant results, many patients do not benefit from anti-PD-1/PD-L1. This is because of the potential for malignancies to co-opt myriad immunosuppressive mechanisms other than aberrant expression of PD-L1. Conceptually, these can be divided into three categories. First, for some patients there is likely a failure to generate sufficient functional tumor antigen-specific T cells. Second, for others, tumor antigen-specific T cells may be generated but fail to enter into the tumor parenchyma. Finally, there are a large number of immunosuppressive mechanisms that have the potential to be operational within the tumor microenvironment: surface membrane immune checkpoint proteins PD-1, CTLA-4, LAG3, TIM3, BTLA, and adenosine A2AR; soluble factors and metabolic alterations interleukin (IL)-10, transforming growth factor (TGF)-β, adenosine, IDO, and arginase; and inhibitory cells, cancer-associated fibroblasts (CAFs), regulatory T cells, myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages. In this article, we discuss three strategies to generate more tumor-reactive T cells for patients: anti-CTLA-4, therapeutic tumor vaccination, and adoptive cellular therapy, with T cells redirected to tumor antigens using T-cell receptor (TCR) or chimeric antigen receptor (CAR) gene modification. We also review some of the various strategies in development to thwart tumor microenvironment immunosuppressive mechanisms. Strategies to drive more T cells into tumors remain a significant challenge.

  3. Immunotherapy: Beyond Anti-PD-1 and Anti-PD-L1 Therapies.

    PubMed

    Antonia, Scott J; Vansteenkiste, Johan F; Moon, Edmund

    2016-01-01

    Advanced-stage non-small cell lung cancer (NSCLC) and small cell lung cancer are cancers in which chemotherapy produces a survival benefit, although it is small. We now know that anti-PD-1/PD-L1 has substantial clinical activity in both of these diseases, with an overall response rate (ORR) of 15%-20%. These responses are frequently rapid and durable, increase median overall survival (OS) compared with chemotherapy, and produce long-term survivors. Despite these very significant results, many patients do not benefit from anti-PD-1/PD-L1. This is because of the potential for malignancies to co-opt myriad immunosuppressive mechanisms other than aberrant expression of PD-L1. Conceptually, these can be divided into three categories. First, for some patients there is likely a failure to generate sufficient functional tumor antigen-specific T cells. Second, for others, tumor antigen-specific T cells may be generated but fail to enter into the tumor parenchyma. Finally, there are a large number of immunosuppressive mechanisms that have the potential to be operational within the tumor microenvironment: surface membrane immune checkpoint proteins PD-1, CTLA-4, LAG3, TIM3, BTLA, and adenosine A2AR; soluble factors and metabolic alterations interleukin (IL)-10, transforming growth factor (TGF)-β, adenosine, IDO, and arginase; and inhibitory cells, cancer-associated fibroblasts (CAFs), regulatory T cells, myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages. In this article, we discuss three strategies to generate more tumor-reactive T cells for patients: anti-CTLA-4, therapeutic tumor vaccination, and adoptive cellular therapy, with T cells redirected to tumor antigens using T-cell receptor (TCR) or chimeric antigen receptor (CAR) gene modification. We also review some of the various strategies in development to thwart tumor microenvironment immunosuppressive mechanisms. Strategies to drive more T cells into tumors remain a significant challenge. PMID

  4. Prognostic value of PD-L1 and PD-1 expression in pulmonary neuroendocrine tumors

    PubMed Central

    Fan, Yangwei; Ma, Ke; Wang, Chuying; Ning, Jing; Hu, Yuan; Dong, Danfeng; Dong, Xuyuan; Geng, Qianqian; Li, Enxiao; Wu, Yinying

    2016-01-01

    Purpose Programmed death 1 (PD-1) receptor and its ligand, programmed death ligand-1 (PD-L1), play critical roles in the immune invasion of various tumors. This study aimed to explore the clinical significance of PD-L1/PD-1 expression in the progression of pulmonary neuroendocrine tumors (PNETs). Methods The expression of PD-L1 and PD-1 in 80 patients diagnosed with PNETs were investigated. Immunohistochemical analysis was performed on 80 formalin-fixed paraffin-embedded tissue specimens from PNETs and 20 corresponding cancer-adjacent tissue specimens. Results Tissues from PNETs had higher levels of PD-L1 (58.8%) and PD-1 (51.3%) compared to the cancer-adjacent tissues (25% and 20%, respectively). Meanwhile, PD-L1 expression was associated with PD-1 expression (P=0.007). PD-L1 expression was significantly associated with histological type (P=0.014) and tumor stage (P=0.014). Univariate analyses showed that the overall survival time of PNETs patients was significantly associated with PD-L1 expression in cancer cells (P=0.003), PD-1 expression in tumor-infiltrating lymphocytes (P=0.001), tumor node metastasis stage (P<0.05), and distant metastasis (P<0.001). Additionally, multivariate analysis revealed that PD-L1 expression, PD1 expression, and distant metastasis of PNETs were independently associated with survival time. Moreover, Kaplan–Meier survival curves analysis revealed that patients with negative PD-L1 and PD-1 expression had better prognoses. Conclusion Data suggested that PD-L1 and PD-1 can be useful prognostic biomarkers for survival and can pave the way toward new immunotherapy regimens against PNETs through targeting the PD-L1/PD-1 pathway. PMID:27785054

  5. Palliative communications: addressing chemotherapy in patients with advanced cancer.

    PubMed

    Kadakia, K C; Moynihan, T J; Smith, T J; Loprinzi, C L

    2012-04-01

    Patients with advanced cancers often endure chemotherapy late in their disease course leading to unnecessary adverse effects, loss of quality of life, and delay in hospice referral. Compassionate and honest communication about the use of chemotherapy can facilitate better patient care. This manuscript will explore communication issues regarding palliative-intent chemotherapy.

  6. Myofacial Trigger Points in Advanced Cancer Patients

    PubMed Central

    Hasuo, Hideaki; Ishihara, Tatsuhiko; Kanbara, Kenji; Fukunaga, Mikihiko

    2016-01-01

    Myofascial pain syndrome is started to be recognized as one of important factors of pain in cancer patients. However, no reports on features of myofascial trigger points were found in terminally-ill cancer populations. This time, we encountered 5 patients with myofascial pain syndrome and terminal cancer in whom delirium developed due to increased doses of opioid without a diagnosis of myofascial pain syndrome on initial presentation. The delirium subsided with dose reductions of opioid and treatment of myofascial pain syndrome. The common reason for a delayed diagnosis among the patients included an incomplete palpation of the painful sites, which led to unsuccessful myofascial trigger points identification. The features of myofascial trigger points included single onset in the cancer pain management site with opioid and the contralateral abdominal side muscles of the non-common sites. Withdrawal reflexes associated with cancer pain in the supine position, which are increasingly seen in the terminal cancer patients, were considered to have contributed to this siuation. We consider that careful palpation of the painful site is important, in order to obtain greater knowledge and understanding of the features of myofascial trigger points. PMID:26962285

  7. Measuring patient-reported outcomes in advanced gastric cancer

    PubMed Central

    Xu, Jianming; Evans, TR Jeffry; Coon, Cheryl; Copley-Merriman, Kati; Su, Yun

    2013-01-01

    Background Gastric cancer (GC), one of the most common cancers in the world, is often diagnosed at an advanced stage and associated with a poor prognosis. Quality of life and patient-reported outcomes (PROs) are important considerations when treating GC patients. The aim of this study was to identify existing PRO instruments that would be appropriate for use in GC trials. Methods Data were obtained from a systematic literature review and interviews with clinical experts. A literature search was conducted using OVID (EMBASE and MEDLINE) and yielded 1,008 abstracts; 92 assessed PROs in an advanced GC. Results Key symptoms and functional impacts identified through the literature and expert input included abdominal pain or pain at the site of distant metastases, dysphagia and other symptoms related to eating, and digestive symptoms. The liver and lungs were the most frequent locations of metastases, leading to dyspnea, abdominal fullness, and jaundice. Symptoms related to changes in bowel habits appeared to be more frequent and pronounced in Asian patients, possibly due to the higher prevalence of GC in the body of the stomach in this population. The five most commonly used PRO instruments were identified, but their validity in advanced-stage GC patients remains unclear. Conclusions The symptoms and functional impacts identified here should be confirmed with robust input from advanced-stage GC patients. Optimal measurement of PROs in GC should account for patient burden and possible differences between Asian and non-Asian patients. PMID:24062809

  8. PD-L1 expression in the Merkel cell carcinoma microenvironment: Association with inflammation, Merkel cell polyomavirus and overall survival

    PubMed Central

    Loyo, Myriam; Kagohara, Luciane T.; Luber, Brandon S.; Wang, Hao; Xu, Haiying; Nayar, Suresh K.; Wang, Timothy S.; Sidransky, David; Anders, Robert A.; Topalian, Suzanne L.; Taube, Janis M.

    2013-01-01

    Merkel cell carcinoma (MCC) is a lethal, virus-associated cancer that lacks effective therapies for advanced disease. Agents blocking the PD-1/PD-L1 pathway have demonstrated objective, durable tumor regressions in patients with advanced solid malignancies and efficacy has been linked to PD-L1 expression in the tumor microenvironment. To investigate whether MCC might be a target for PD-1/PD-L1 blockade, we examined MCC PD-L1 expression, its association with tumor-infiltrating lymphocytes (TILs), Merkel cell polyomavirus (MCPyV), and overall survival. Sixty-seven MCC specimens from 49 patients were assessed with immunohistochemistry for PD-L1 expression by tumor cells and TILs, and immune infiltrates were characterized phenotypically. Tumor cell and TIL PD-L1 expression were observed in 49% and 55% of patients, respectively. In specimens with PD-L1(+) tumor cells, 97% (28/29) demonstrated a geographic association with immune infiltrates. Among specimens with moderate-severe TIL intensities, 100% (29/29) demonstrated PD-L1 expression by tumor cells. Significant associations were also observed between the presence of MCPyV DNA, a brisk inflammatory response, and tumor cell PD-L1 expression: MCPyV(−) tumor cells were uniformly PD-L1(−). Taken together, these findings suggest that a local tumor-specific and potentially MCPyV-specific immune response drives tumor PD-L1 expression, similar to previous observations in melanoma and head and neck squamous cell carcinomas. In multivariate analyses, PD-L1(−) MCCs were independently associated with worse overall survival (hazard ratio 3.12; 95% CI, 1.28-7.61; p=0.012). These findings suggest that an endogenous immune response promotes PD-L1 expression in the MCC microenvironment when MCPyV is present, and provide a rationale for investigating therapies blocking PD-1/PD-L1 for patients with MCC. PMID:24416729

  9. Assessing circadian rhythms in propofol PK and PD during prolonged infusion in ICU patients.

    PubMed

    Bienert, Agnieszka; Kusza, Krzysztof; Wawrzyniak, Katarzyna; Grześkowiak, Edmund; Kokot, Zenon J; Matysiak, Jan; Grabowski, Tomasz; Wolc, Anna; Wiczling, Paweł; Regulski, Miłosz

    2010-06-01

    This study evaluates possible circadian rhythms during prolonged propofol infusion in patients in the intensive care unit. Eleven patients were sedated with a constant propofol infusion. The blood samples for the propofol assay were collected every hour during the second day, the third day, and after the termination of the propofol infusion. Values of electroencephalographic bispectral index (BIS), arterial blood pressure, heart rate, blood oxygen saturation and body temperature were recorded every hour at the blood collection time points. A two-compartment model was used to describe propofol pharmacokinetics. Typical values of the central and peripheral volume of distribution and inter-compartmental clearance were V(C) = 27.7 l, V(T) = 801 l, and CL(D) = 2.73 l/min. The systolic blood pressure (SBP) was found to influence the propofol metabolic clearance according to Cl (l/min) = 2.65 x (1-0.00714 x (SBP-135)). There was no significant circadian rhythm detected with respect to propofol pharmacokinetics. The BIS score was assessed as a direct effect model with EC(50) equal 1.98 mg/l. There was no significant circadian rhythm detected within the BIS scores. We concluded that the light-dark cycle did not influence propofol pharmacokinetics and pharmacodynamics in intensive care units patients. The lack of night-day differences was also noted for systolic blood pressure, diastolic blood pressure and blood oxygenation. Circadian rhythms were detected for heart rate and body temperature, however they were severely disturbed from the pattern of healthy patients.

  10. Assessing circadian rhythms in propofol PK and PD during prolonged infusion in ICU patients

    PubMed Central

    Kusza, Krzysztof; Wawrzyniak, Katarzyna; Grześkowiak, Edmund; Kokot, Zenon J.; Matysiak, Jan; Grabowski, Tomasz; Wolc, Anna; Wiczling, Paweł; Regulski, Miłosz

    2010-01-01

    This study evaluates possible circadian rhythms during prolonged propofol infusion in patients in the intensive care unit. Eleven patients were sedated with a constant propofol infusion. The blood samples for the propofol assay were collected every hour during the second day, the third day, and after the termination of the propofol infusion. Values of electroencephalographic bispectral index (BIS), arterial blood pressure, heart rate, blood oxygen saturation and body temperature were recorded every hour at the blood collection time points. A two-compartment model was used to describe propofol pharmacokinetics. Typical values of the central and peripheral volume of distribution and inter-compartmental clearance were VC = 27.7 l, VT = 801 l, and CLD = 2.73 l/min. The systolic blood pressure (SBP) was found to influence the propofol metabolic clearance according to Cl (l/min) = 2.65·(1 − 0.00714·(SBP − 135)). There was no significant circadian rhythm detected with respect to propofol pharmacokinetics. The BIS score was assessed as a direct effect model with EC50 equal 1.98 mg/l. There was no significant circadian rhythm detected within the BIS scores. We concluded that the light–dark cycle did not influence propofol pharmacokinetics and pharmacodynamics in intensive care units patients. The lack of night–day differences was also noted for systolic blood pressure, diastolic blood pressure and blood oxygenation. Circadian rhythms were detected for heart rate and body temperature, however they were severely disturbed from the pattern of healthy patients. PMID:20544262

  11. Sarcopenia and physical function in overweight patients with advanced cancer.

    PubMed

    Prado, Carla M M; Lieffers, Jessica R; Bowthorpe, Lindsay; Baracos, Vickie E; Mourtzakis, Marina; McCargar, Linda J

    2013-01-01

    Advanced cancer is associated with numerous metabolic abnormalities that may lead to significant body composition changes, particularly muscle loss or sarcopenia. Sarcopenia in cancer has been associated with poor clinical outcomes, including poor physical function. Accurate tools to assess body composition are expensive and not readily available in clinical settings. Unfortunately, little is known about the efficacy of affordable and portable techniques to assess functional status in patients with cancer. We investigated the prevalence of sarcopenia and its association with different portable and low-cost functional status measurement tools (i.e., handgrip strength testing, a two-minute walking test, and a self-report questionnaire) in overweight/obese patients (body mass index ≥ 25 kg/m²) with advanced cancer. Twenty-eight patients (68% men) aged 64.5 ± 9.5 years with advanced lung or colorectal cancer were included. Sarcopenia was assessed by measuring appendicular skeletal muscle (ASM) adjusted by height (ASM index), using dual energy X-ray absorptiometry. Approximately 36% of patients had sarcopenia. Average handgrip strength was greater in men without sarcopenia than in men with it (p=0.035). In men, ASM index was positively correlated with average (r=0.535, p=0.018) and peak handgrip strength (r=0.457, p=0.049). No differences were observed among female patients. Handgrip strength was associated with sarcopenia in male patients with advanced cancer, and therefore it may be used as a portable and simple nutritional screening tool.

  12. PD-1/PD-L1 expression in extra-medullary lesions of multiple myeloma.

    PubMed

    Crescenzi, Anna; Annibali, Ombretta; Bianchi, Antonella; Pagano, Anastasia; Donati, Michele; Grifoni, Alba; Avvisati, Giuseppe

    2016-10-01

    Multiple myeloma patients may develop extraosseous involvement in the course of the disease making prognosis very poor and new drugs clearly needed. The PD-1/PD-L1 axis has emerged as a master immune checkpoint in antitumor responses and recent studies investigated the role of PD-L1 in multiple myeloma cells; no data however are still available about PD-L1 expression in extramedullary localizations. We demonstrate PD-L1 expression in 4/12 cases of extraosseous myeloma suggesting that these lesions represent a specialized microenvironment. We found presence of PD-1+ infiltrating lymphocytes in all observed cases supporting the relevance of PD-1/PD-L1 checkpoint in extramedullary myeloma. We also investigated the correlation in PD1/PD-L1 staining between marrow staining and EMP lesions. PMID:27619200

  13. Palliative care for patients with advance chronic kidney disease.

    PubMed

    Douglas, C A

    2014-01-01

    Over the past three decades there has been a dramatic rise in the number of patients with advanced chronic kidney disease. The fastest expanding group receiving dialysis has been the elderly. However, for those patients who are very elderly with co-morbidity, dialysis may not offer a survival advantage. Therefore, active conservative management is a growing service offered by many renal units in the UK and focuses on non-dialytic correction of fluid and electrolyes, management of renal anaemia, and assessment and management of symptoms. The five-year survival of a patient over 75 years of age starting dialysis is 20% and if a patient is over 75 years, has co-morbidity, or a poor performance status, dialysis may not offer any survival advantage. Whether a patient is managed by dialysis or by conservative management the symptom burden suffered is high. These symptoms are under-recognised and often managed poorly because of increased drug toxicity in renal failure. This complex group of patients require close working between renal, palliative care, medicine for the elderly, and community teams, to allow best quality of life and end of life care. This review describes some of the challenges in providing Advanced Care Planning for dialysis and conservatively managed patients, highlights the symptom burden of patients with advanced chronic kidney disease, and offers guidance in how to manage the symptoms effectively.

  14. [Integrated care for patients with advanced chronic obstructive pulmonary disease].

    PubMed

    Jassem, Ewa; Górecka, Dorota; Krakowiak, Piotr; Kozielski, Jerzy; Słomiński, J Marek; Krajnik, Małgorzata; Fal, Andrzej M

    2010-01-01

    Chronic obstructive pulmonary disease (COPD) is the third cause of mortality and disability (assessed by DALY) among patients above 60 year old. Severe and very severe COPD (FEV(1) = equal or less than 50% and 30% of expected value, respectively) is estimated at 20% of all COPD patients. Advanced COPD usually leads to physical and mental deterioration, the patients often manage with the problems caused by the disease and other comorbidities poorly. This leads to increased risk of COPD exacerbations and further deterioration of the patient's status, increased costs of medical care and eventually increased risk of death. Current organization of medical care for those patients does not provide adequate health and social support for them. However, it seems that introducing an integrated approach proposed by World Health Organization, could improve the situation of advanced COPD patients. In Poland, this kind of care has been provided in advanced cancer patients throughout stationary palliative care units and hospices during the last several years. This experience should be helpful in integrating actions of general practitioners and specialized nurses, as well as providing access for the specialists' consultations according to the individual needs of the patients. It should also allow for broad cooperation with auxiliary staff, such as social workers, medical assistants and volunteers, as well as psychologists and clergymen (especially in the terminal phase of the disease).

  15. Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer

    PubMed Central

    Topalian, Suzanne L.; Hodi, F. Stephen; Brahmer, Julie R.; Gettinger, Scott N.; Smith, David C.; McDermott, David F.; Powderly, John D.; Carvajal, Richard D.; Sosman, Jeffrey A.; Atkins, Michael B.; Leming, Philip D.; Spigel, David R.; Antonia, Scott J.; Horn, Leora; Drake, Charles G.; Pardoll, Drew M.; Chen, Lieping; Sharfman, William H.; Anders, Robert A.; Taube, Janis M.; McMiller, Tracee L.; Xu, Haiying; Korman, Alan J.; Jure-Kunkel, Maria; Agrawal, Shruti; McDonald, Daniel; Kollia, Georgia D.; Gupta, Ashok; Wigginton, Jon M.; Sznol, Mario

    2012-01-01

    Background Blockade of programmed death 1 (PD-1), an inhibitory receptor expressed by T cells, can overcome immune resistance. We assessed the antitumor activity and safety of BMS-936558, an antibody that specifically blocks PD-1. Methods We enrolled patients with advanced melanoma, non–small-cell lung cancer, castration-resistant prostate cancer, or renal-cell or colorectal cancer to receive anti–PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks. Response was assessed after each 8-week treatment cycle. Patients received up to 12 cycles until disease progression or a complete response occurred. Results A total of 296 patients received treatment through February 24, 2012. Grade 3 or 4 drug-related adverse events occurred in 14% of patients; there were three deaths from pulmonary toxicity. No maximum tolerated dose was defined. Adverse events consistent with immune-related causes were observed. Among 236 patients in whom response could be evaluated, objective responses (complete or partial responses) were observed in those with non–small-cell lung cancer, melanoma, or renal-cell cancer. Cumulative response rates (all doses) were 18% among patients with non–small-cell lung cancer (14 of 76 patients), 28% among patients with melanoma (26 of 94 patients), and 27% among patients with renal-cell cancer (9 of 33 patients). Responses were durable; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up. To assess the role of intratumoral PD-1 ligand (PD-L1) expression in the modulation of the PD-1–PD-L1 pathway, immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients. Of 17 patients with PD-L1–negative tumors, none had an objective response; 9 of 25 patients (36%) with PD-L1–positive tumors had an objective response (P = 0.006). Conclusions Anti–PD-1 antibody produced objective responses in approximately one in four to one in five patients with non

  16. PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation.

    PubMed

    Kong, Y; Zhang, J; Claxton, D F; Ehmann, W C; Rybka, W B; Zhu, L; Zeng, H; Schell, T D; Zheng, H

    2015-07-31

    Prognosis of leukemia relapse post allogeneic stem cell transplantation (alloSCT) is poor and effective new treatments are urgently needed. T cells are pivotal in eradicating leukemia through a graft versus leukemia (GVL) effect and leukemia relapse is considered a failure of GVL. T-cell exhaustion is a state of T-cell dysfunction mediated by inhibitory molecules including programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3). To evaluate whether T-cell exhaustion and inhibitory pathways are involved in leukemia relapse post alloSCT, we performed phenotypic and functional studies on T cells from peripheral blood of acute myeloid leukemia patients receiving alloSCT. Here we report that PD-1(hi)TIM-3(+) cells are strongly associated with leukemia relapse post transplantation. Consistent with exhaustion, PD-1(hi)TIM-3(+) T cells are functionally deficient manifested by reduced production of interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). In addition, these cells demonstrate a phenotype consistent with exhausted antigen-experienced T cells by losing TN and TEMRA subsets. Importantly, increase of PD-1(hi)TIM-3(+) cells occurs before clinical diagnosis of leukemia relapse, suggesting their predictive value. Results of our study provide an early diagnostic approach and a therapeutic target for leukemia relapse post transplantation.

  17. PD-1, PD-L1, PD-L2 expression in the chordoma microenvironment

    PubMed Central

    Mathios, Dimitrios; Ruzevick, Jacob; Jackson, Christopher M.; Xu, Haiying; Shah, Sagar; Taube, Janis M.; Burger, Peter C.; McCarthy, Edward F.; Quinones-Hinojosa, Alfredo; Pardoll, Drew M.

    2015-01-01

    Chordomas are rare malignant tumors that are postulated to arise from remnants of the notochord. Currently, the interaction between chordomas and the host immune system is poorly understood. The checkpoint protein, PD-1 is expressed by circulating lymphocytes and is a marker of activation and exhaustion. Its ligands, PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273), are expressed on a variety of human cancers; however this pathway has not been previously reported in chordomas. We used flow cytometric and RT-PCR analysis in three established primary and recurrent chordoma cell lines (U-CH1, U-CH2, and JHC7) as well as immunohistochemical analysis of chordoma tissues from 10 patients to identify and localize expression of PD-1 pathway proteins. PD-1 ligands are not constitutively expressed by chordoma cells, but their expression is induced in the setting of pro-inflammatory cytokines in all cell lines examined. In paraffin embedded tissues, we found that tumor infiltrating lymphocytes expressed PD-1 in 3/6 cases. We also found that, although chordoma cells did not express significant levels of PD-L1, PD-L1 expression was observed on tumor-infiltrating macrophages and tumor infiltrating lymphocytes. Our study suggests that PD-1, PD-L1, and PD-L2 are present in the microenvironment of a subset of chordomas analyzed. Future studies are needed to evaluate the contribution of the PD-1 pathway to the immunosuppressive microenvironment of chordomas. PMID:25349132

  18. A new biomarker for subthalamic deep brain stimulation for patients with advanced Parkinson’s disease—a pilot study

    NASA Astrophysics Data System (ADS)

    Gmel, Gerrit E.; Hamilton, Tara J.; Obradovic, Milan; Gorman, Robert B.; Single, Peter S.; Chenery, Helen J.; Coyne, Terry; Silburn, Peter A.; Parker, John L.

    2015-12-01

    Objective. Deep brain stimulation (DBS) has become the standard treatment for advanced stages of Parkinson’s disease (PD) and other motor disorders. Although the surgical procedure has improved in accuracy over the years thanks to imaging and microelectrode recordings, the underlying principles that render DBS effective are still debated today. The aim of this paper is to present initial findings around a new biomarker that is capable of assessing the efficacy of DBS treatment for PD which could be used both as a research tool, as well as in the context of a closed-loop stimulator. Approach. We have used a novel multi-channel stimulator and recording device capable of measuring the response of nervous tissue to stimulation very close to the stimulus site with minimal latency, rejecting most of the stimulus artefact usually found with commercial devices. We have recorded and analyzed the responses obtained intraoperatively in two patients undergoing DBS surgery in the subthalamic nucleus (STN) for advanced PD. Main results. We have identified a biomarker in the responses of the STN to DBS. The responses can be analyzed in two parts, an initial evoked compound action potential arising directly after the stimulus onset, and late responses (LRs), taking the form of positive peaks, that follow the initial response. We have observed a morphological change in the LRs coinciding with a decrease in the rigidity of the patients. Significance. These initial results could lead to a better characterization of the DBS therapy, and the design of adaptive DBS algorithms that could significantly improve existing therapies and help us gain insights into the functioning of the basal ganglia and DBS.

  19. CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients

    PubMed Central

    Su, Shu; Hu, Bian; Shao, Jie; Shen, Bin; Du, Juan; Du, Yinan; Zhou, Jiankui; Yu, Lixia; Zhang, Lianru; Chen, Fangjun; Sha, Huizi; Cheng, Lei; Meng, Fanyan; Zou, Zhengyun; Huang, Xingxu; Liu, Baorui

    2016-01-01

    Strategies that enhance the function of T cells are critical for immunotherapy. One negative regulator of T-cell activity is ligand PD-L1, which is expressed on dentritic cells (DCs) or some tumor cells, and functions through binding of programmed death-1 (PD-1) receptor on activated T cells. Here we described for the first time a non-viral mediated approach to reprogram primary human T cells by disruption of PD-1. We showed that the gene knockout of PD-1 by electroporation of plasmids encoding sgRNA and Cas9 was technically feasible. The disruption of inhibitory checkpoint gene PD-1 resulted in significant reduction of PD-1 expression but didn’t affect the viability of primary human T cells during the prolonged in vitro culture. Cellular immune response of the gene modified T cells was characterized by up-regulated IFN-γ production and enhanced cytotoxicity. These results suggest that we have demonstrated an approach for efficient checkpoint inhibitor disruption in T cells, providing a new strategy for targeting checkpoint inhibitors, which could potentialy be useful to improve the efficacy of T-cell based adoptive therapies. PMID:26818188

  20. CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients.

    PubMed

    Su, Shu; Hu, Bian; Shao, Jie; Shen, Bin; Du, Juan; Du, Yinan; Zhou, Jiankui; Yu, Lixia; Zhang, Lianru; Chen, Fangjun; Sha, Huizi; Cheng, Lei; Meng, Fanyan; Zou, Zhengyun; Huang, Xingxu; Liu, Baorui

    2016-01-28

    Strategies that enhance the function of T cells are critical for immunotherapy. One negative regulator of T-cell activity is ligand PD-L1, which is expressed on dentritic cells (DCs) or some tumor cells, and functions through binding of programmed death-1 (PD-1) receptor on activated T cells. Here we described for the first time a non-viral mediated approach to reprogram primary human T cells by disruption of PD-1. We showed that the gene knockout of PD-1 by electroporation of plasmids encoding sgRNA and Cas9 was technically feasible. The disruption of inhibitory checkpoint gene PD-1 resulted in significant reduction of PD-1 expression but didn't affect the viability of primary human T cells during the prolonged in vitro culture. Cellular immune response of the gene modified T cells was characterized by up-regulated IFN-γ production and enhanced cytotoxicity. These results suggest that we have demonstrated an approach for efficient checkpoint inhibitor disruption in T cells, providing a new strategy for targeting checkpoint inhibitors, which could potentialy be useful to improve the efficacy of T-cell based adoptive therapies.

  1. Expression of programmed death-1 ligand (PD-L1) in tumor-infiltrating lymphocytes is associated with favorable spinal chordoma prognosis.

    PubMed

    Zou, Ming-Xiang; Peng, An-Bo; Lv, Guo-Hua; Wang, Xiao-Bin; Li, Jing; She, Xiao-Ling; Jiang, Yi

    2016-01-01

    Aberrant expression of programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) proteins alters human immunoresponse and promotes tumor development and progression. We assessed the expression status of PD-1 and PD-L1 in spinal chordoma tissue specimens and their association with clinicopathological characteristics of patients. Formalin-fixed paraffin-embedded tumor samples from 54 patients with spinal chordoma were collected for immunohistochemical analysis of PD-1 and PD-L1 expression. The association of the expression levels of PD-1 and PD-L1 with clinicopathological variables and survival data were statistically analyzed. Lymphocyte infiltrates were present in all 54 patient samples. Of 54 samples, 37 (68.5%) had both positive PD-1 and PD-L1 expression in tumor cell membrane. Moreover, 38 (70.4%) and 12 (22.2%) had positive PD-1 and PD-L1 expression in tumor-infiltrating lymphocytes (TILs), respectively. Tumors with positive PD-L1 expression were significantly associated with advanced stages of chordoma (p = 0.041) and TIL infiltration (p = 0.005), and had a borderline association with tumor grade (p = 0.051). However, positive tumor PD-L1 expression was not significantly associated with local recurrence-free survival (LRFS) or overall survival (OS). PD-1 expression in TILs was associated with poor LRFS (χ(2) = 10.051, p = 0.002, log-rank test). Multivariate analysis showed that PD-L1 expression only in TILs was an independent predictor for LRFS (HR = 0.298, 95% CI: 0.098-0.907, p = 0.033), and OS (HR = 0.188, 95% CI: 0.051-0.687, p = 0.011) in spinal chordoma patients. In conclusion, PD-L1 expression in TILs was an independent predictor for both LRFS and OS in spinal chordoma patients. Our findings suggest that the PD-1/PD-L1 pathway may be a novel therapeutic target for the immunotherapy of chordoma.

  2. Expression of programmed death-1 ligand (PD-L1) in tumor-infiltrating lymphocytes is associated with favorable spinal chordoma prognosis

    PubMed Central

    Zou, Ming-Xiang; Peng, An-Bo; Lv, Guo-Hua; Wang, Xiao-Bin; Li, Jing; She, Xiao-Ling; Jiang, Yi

    2016-01-01

    Aberrant expression of programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) proteins alters human immunoresponse and promotes tumor development and progression. We assessed the expression status of PD-1 and PD-L1 in spinal chordoma tissue specimens and their association with clinicopathological characteristics of patients. Formalin-fixed paraffin-embedded tumor samples from 54 patients with spinal chordoma were collected for immunohistochemical analysis of PD-1 and PD-L1 expression. The association of the expression levels of PD-1 and PD-L1 with clinicopathological variables and survival data were statistically analyzed. Lymphocyte infiltrates were present in all 54 patient samples. Of 54 samples, 37 (68.5%) had both positive PD-1 and PD-L1 expression in tumor cell membrane. Moreover, 38 (70.4%) and 12 (22.2%) had positive PD-1 and PD-L1 expression in tumor-infiltrating lymphocytes (TILs), respectively. Tumors with positive PD-L1 expression were significantly associated with advanced stages of chordoma (p = 0.041) and TIL infiltration (p = 0.005), and had a borderline association with tumor grade (p = 0.051). However, positive tumor PD-L1 expression was not significantly associated with local recurrence-free survival (LRFS) or overall survival (OS). PD-1 expression in TILs was associated with poor LRFS (χ2 = 10.051, p = 0.002, log-rank test). Multivariate analysis showed that PD-L1 expression only in TILs was an independent predictor for LRFS (HR = 0.298, 95% CI: 0.098-0.907, p = 0.033), and OS (HR = 0.188, 95% CI: 0.051-0.687, p = 0.011) in spinal chordoma patients. In conclusion, PD-L1 expression in TILs was an independent predictor for both LRFS and OS in spinal chordoma patients. Our findings suggest that the PD-1/PD-L1 pathway may be a novel therapeutic target for the immunotherapy of chordoma. PMID:27508049

  3. An overview of advance care planning for patients with advanced chronic kidney disease: The basics.

    PubMed

    Wasylynuk, Betty Ann; Davison, Sara N

    2016-01-01

    As the number of Canadians living with end-stage kidney disease (ESKD) continues to grow, even higher numbers are living with advanced chronic kidney disease (CKD). Many of these people will eventually require renal replacement therapy (RRT), either dialysis or transplantation. More than 50% of patients starting RRT today are aged 65 or older, with the fastest growing group being patients 75 years and older. Despite advances to dialysis technology and dialysis care, the mortality rates remain high and dialysis patients' end-of-life care may not align with their preferences or values. Advance care planning (ACP) is an essential component of quality comprehensive kidney care. Kidney care teams develop strong relationships with their patients and are well positioned to integrate ACP into routine kidney care. This article defines ACP, outlines the essential components of ACP, and discusses the benefits, challenges, and special considerations of ACP. By enhancing the kidney care team's understanding of ACP, this article aims to assist in integrating ACP into routine kidney care for patients with advanced CKD. PMID:27215058

  4. Necrotising herpetic retinopathy in patients with advance HIV disease.

    PubMed Central

    Miller, R F; Brink, N S; Cartledge, J; Sharvell, Y; Frith, P

    1997-01-01

    OBJECTIVES: To describe the presenting features, clinical and laboratory diagnosis, response to treatment, and outcome of necrotising herpetic retinopathy (NHR) in HIV infected patients. METHODS: Retrospective case records/laboratory data review of five HIV infected patients presenting to the specialist HIV/AIDS unit at UCL Hospitals, London from April 1994 to August 1996 with a clinical diagnosis of NHR. RESULTS: All patients had advanced HIV disease with a median CD4 count of 20.10(6)/1. Three patients had cutaneous varicella zoster virus (VZV) infection within the preceding 8 weeks. All had uniocular loss of visual acuity; one also had headache and another ocular pain. All had typical retinal appearances. VZV DNA was detected in cerebrospinal fluid of four patients (and in vitreous fluid of one of the four) and in vitreous fluid of one other. One patient refused therapy and rapidly became blind. Four patients received intravenous foscarnet with intravenous aciclovir for 6 weeks: three subsequently received oral famciclovir and one oral valaciclovir; two patients also had intravitreal injections of foscarnet. In none of the four did treatment bring about improvement in visual acuity, but in all four visual loss from retinitis was halted. CONCLUSIONS: NHR occurs in HIV infected patients with advanced HIV disease and is strongly associated with evidence of VZV infection. With aggressive use of antiviral drugs the outcome is not uniformly poor. Images PMID:9582461

  5. Prognosis of morbid obesity patients with advanced heart failure.

    PubMed

    Nagarajan, Vijaiganesh; Cauthen, Clay A; Starling, Randall C; Tang, Wai Hong Wilson

    2013-01-01

    Obese patients have been noted to have better prognosis in many conditions including heart failure. We hypothesize that this favorable prognosis for obesity may not be seen in patients with morbid obesity and advanced heart failure. A total of 501 consecutive patients with advanced heart failure referred for heart transplant evaluation to the Cleveland Clinic were studied. Patients were categorized into 3 groups based on their body mass index score as nonobese (≤30 kg/m(2) ), obese (30.1-40 kg/m(2) ), and morbidly obese (≥40 kg/m(2) ). There were fewer cardiovascular risk factors in the morbidly obese group. Unadjusted event-free survival rates were 48.4%, 57.4%, and 28.6% in the nonobese, obese, and morbidly obese groups, respectively (P=.02). In univariate analysis, both the nonobese group (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.09-1.91; P=.01) and the morbidly obese group (HR, 2.46; 95% CI, 1.40-4.30; P=.002) had significantly higher risk of all-cause mortality/transplantation compared with the obese group. This difference persisted in multivariate analysis after adjustment for confounding factors. Our study re-emphasizes the presence of an obesity paradox even in patients with very advanced heart failure. This favorable prognosis, however, may not be relevant in patients with morbidly obesity. Cardiovascular risk factors may not contribute to this phenomenon.

  6. Effects of neurostimulation for advanced Parkinson’s disease patients on motor symptoms: A multiple-treatments meta-analysas of randomized controlled trials

    PubMed Central

    Xie, Cheng-Long; Shao, Bei; Chen, Jie; Zhou, Yi; Lin, Shi-Yi; Wang, Wen-Wen

    2016-01-01

    Deep brain stimulation (DBS) is the surgical procedure of choice for patients with advanced Parkinson disease (PD). We aim to evaluate the efficacy of GPi (globus pallidus internus), STN (subthalamic nucleus)-DBS and medical therapy for PD. We conducted a systematic review and multiple-treatments meta-analysis to investigate the efficacy of neurostimulation and medical therapy for PD patients. Sixteen eligible studies were included in this analysis. We pooled the whole data and found obvious difference between GPi-DBS versus medical therapy and STN-DBS versus medical therapy in terms of UPDRS scores (Unified Parkinson’s Disease Rating Scale). Meanwhile, we found GPi-DBS had the similar efficacy on the UPDRS scores when compared with STN-DBS. What is more, quality of life, measured by PDQ-39 (Parkinson’s disease Questionnaire) showed greater improvement after GPi-DBS than STN-DBS. Five studies showed STN-DBS was more effective for reduction in medication than GPi-DBS. Overall, either GPi-DBS or STN-DBS was an effective technique to control PD patients’ symptoms and improved their functionality and quality of life. Meanwhile, the UPDRS scores measuring parkinsonian symptoms revealed no significant difference between GPi-DBS and STN-DBS. STN-DBS was more effective for reduction in medication than GPi-DBS. Alternatively, GPi-DBS was more effective for improving the PDQ-39 score than STN-DBS. PMID:27142183

  7. Dosimetric parameters as predictive factors for biochemical control in patients with higher risk prostate cancer treated with Pd-103 and supplemental beam radiation

    SciTech Connect

    Orio, Peter; Wallner, Kent . E-mail: kent.Wallner@med.va.gov; Merrick, Gregory; Herstein, Andrew; Mitsuyama, Paul; Thornton, Ken; Butler, Wayne; Sutlief, Steven

    2007-02-01

    Purpose: To analyze the role of dosimetric quality parameters in maximizing cancer eradication in higher risk prostate cancer patients treated with palladium (Pd)-103 and supplemental beam radiation. Methods: One-hundred-seventy-nine patients treated with Pd-103 and supplemental beam radiation, with minimum 2 years follow-up prostate-specific antigen (PSA) values and posttreatment computed tomography scans were analyzed. Dosimetric parameters included the V100 (percent of the postimplant volume covered by the prescription dose), the D90 (the minimum dose that covered 90% of the post implant volume), and the treatment margins (the radial distance between the prostatic edge and the prescription isodose). Treatment margins (TMs) were calculated using premarket software. Results: Freedom from biochemical failure was 79% at 3 years, with 92 of the 179 patients (51%) followed beyond 3 years. In comparing patients who did or did not achieve biochemical control, the most striking differences were in biologic factors of pretreatment PSA and Gleason score. The V100, D90, and average TM all showed nonsignificant trends to higher values in patients with biochemical control. In multivariate analysis of each of the three dosimetric parameters against PSA and Gleason score, TM showed the strongest correlation with biochemical control (p = 0.19). Conclusions: For patients with intermediate and high-risk prostate cancer treated with Pd-103 brachytherapy and external beam radiation, biologic factors (PSA and Gleason score) were the most important determinants of cancer eradication. However, there is a trend to better outcomes among patients with higher quality implant parameters, suggesting that attention to implant quality will maximize the likelihood of cure.

  8. A Review of Recent Advances in Perioperative Patient Safety

    PubMed Central

    Fowler, Alexander J.

    2013-01-01

    Major complications in surgery affect up to 16% of surgical procedures. Over the past 50 years, many patient safety initiatives have attempted to reduce such complications. Since the formation of the National Patient Safety Agency in 2001, there have been major advances in patient safety. Most recently, the production and implementation of the Surgical Safety Checklist by the World Health Organisation (WHO), a checklist ensuring that certain ‘never events’ (wrong-site surgery, wrong operation etc.) do not occur, irrespective of healthcare allowance. In this review, a summary of recent advances in patient safety are considered – including improvements in communication, understanding of human factors that cause mistakes, and strategies developed to minimise these. Additionally, the synthesis of best medical practice and harm minimisation is examined, with particular emphasis on communication and appreciation of human factors in the operating theatre. This is based on the resource management systems developed in other high risk industries (e.g. nuclear), and has also been adopted for other high risk medical areas. The WHO global movement to reduce surgical mortality has been highly successful, especially in the healthcare systems of developing nations where mortality reductions of up to 50% have been observed, and reductions in patient complications of 4%. Incident reporting has long been a key component of patient safety and continues to be so; allowing reflection and improved guideline formation. All patients are placed at risk in the surgical environment. It is crucial that this risk is minimised, whilst optimising the patient's outcome. In this review, recent advances in perioperative patient safety are examined and placed in context. PMID:26977290

  9. Orphan symptoms in advanced cancer patients followed at home.

    PubMed

    Mercadante, Sebastiano; Porzio, Giampiero; Valle, Alessandro; Fusco, Flavio; Aielli, Federica; Adile, Claudio; Casuccio, Alessandra

    2013-12-01

    Orphan symptoms are rarely assessed, particularly at home. The aim of this multicenter prospective study was to assess the prevalence of these symptoms and eventual factors possibly associated in advanced cancer patients at admission of a home care program. A prospective study was performed at three home care programs in Italy. Patients' data were collected, including age, sex, diagnosis, and Karnofsky status. Possible contributing factors were analyzed; preexisting neurological diseases, cerebral metastases, hyperthermia, diabetes, a state of dehydration clinically evident and/or oliguria, possible biochemical parameters when available, data regarding recent chemotherapy, opioids and doses, use of neuroleptics, benzodiazepine or anticonvulsants, corticosteroids, anti-inflammatory, and antibiotics were collected. Myoclonus, hiccup, sweating, pruritus, and tenesmus, either rectal or vesical, were assessed, according to a preliminary definition, at time of home care program admission. Three hundred sixty-two patients were surveyed at the three home care programs. Globally, 48 patients presented one or more orphan symptoms in the period taken into consideration, and 7 patients presented more than 1 symptom. One patient presented occasional and diffuse myoclonus. Nineteen patients presented sweating, 13 patients presented pruritus, and 14 patients presented hiccup. Finally, nine patients presented rectal or vesical tenesmus. There was a significant correlation between sweating and transdermal fentanyl use (P = 0.044), fever (P = 0.001), hiccup (P < 0.0005), and vesical tenesmus (P = 0.028). Pruritus was not associated to any factor. Hiccup was associated with gender (males, P = 0.006) and sweating (P < 0.0005). Vesical tenesmus was associated with fever (P = 0.019) and sweating (P = 0.028). Although the symptoms examined have a low prevalence in advanced cancer patients admitted to home care, the distress for patients may be high and

  10. Intraindividual Variability of Nonmotor Fluctuations in Advanced Parkinson's Disease.

    PubMed

    Fauser, Mareike; Löhle, Matthias; Ebersbach, Georg; Odin, Per; Fuchs, Gerd; Jost, Wolfgang H; Chaudhuri, K Ray; Koch, Rainer; Storch, Alexander

    2015-01-01

    Nonmotor symptoms (NMS) fluctuate in conjunction with motor oscillations in advanced Parkinson's disease (PD), though little is known about the variability of NMS fluctuations in individual patients. We aimed to assess within-patient variability in frequency and severity of NMS during a series of five patient-perceived motor On and Off periods in 38 fluctuating PD patients from the multicenter NonMotorFluctuations in PD study using a visual analogue scale. NMS frequency and severity appeared moderately variable in both motor states within individual patients. Symptom severity ranges between motor states showed high variability and were larger in motor Off states for most NMS. PMID:26639660

  11. Nutritional management of the patient with advanced cancer.

    PubMed

    Theologides, A

    1977-02-01

    Protein-calorie malnutrition, vitamin and other deficiencies, and weight loss frequently develop in cancer patients. Although there is no evidence that aggressive nutritional management prolongs survival, it may improve the quality of life. Efforts should be made to maintain adequate daily caloric intake with appropriate food selection and with control of complications interfering with nutrition. In selected patients, intravenous hyperalimentation can provide adequate nutrition during potentially effective chemotherapy or radiotherapy. Elemental diets also may be a source of complete or supplemental nutrition. Further experience with both approaches will help to clarify their role in the nutritional management of the patient with advanced cancer.

  12. The adverse effects of sorafenib in patients with advanced cancers.

    PubMed

    Li, Ye; Gao, Zu-Hua; Qu, Xian-Jun

    2015-03-01

    Sorafenib is the first multi-kinase inhibitor (TKI) approved for the treatment of advanced hepatocellular cancer (HCC) and metastatic renal cell cancer (RCC) and is increasingly being used to treat patients with well-differentiated radioiodine-resistant thyroid cancer (DTC). Sorafenib demonstrates targeted activity on several families of receptor and non-receptor tyrosine kinases that are involved in angiogenesis, tumour growth and metastatic progression of cancer. Sorafenib treatment results in long-term efficacy and low incidence of life-threatening toxicities. Although sorafenib has demonstrated many benefits in patients, the adverse effects cannot be ignored. The most common treatment-related toxicities include diarrhoea, fatigue, hand-foot skin reaction and hypertension. Most of these toxicities are considered mild to moderate and manageable to varying degrees; however, cardiovascular events might lead to death. In this MiniReview, we summarize the adverse effects of sorafenib that commonly occur in patients with advanced cancers. PMID:25495944

  13. Modalities of palliative care in hospitalized patients with advanced AIDS.

    PubMed

    Vincent, I; D'Hérouville, D; Moulin, P; Bugler, C; Fraval, J; Mallet, D; Salamagne, M H; Vildé, J L; Jodelet, D; Leport, C

    2000-04-01

    This prospective multidisciplinary survey started in October 1994. The survey assessed the modalities of care of hospitalized patients with advanced AIDS in an Infectious and Tropical Diseases Unit with regards to the practices of palliative care in a Palliative Care Unit. Seventy-eight (78) AIDS patients with CD4 < or = 30/mm3 who had 102 consecutive hospitalizations were recruited. Types (symptomatic or curative) and number of drugs administered to the patients, as well as biological and radiological investigations performed were recorded. Symptoms were concomitantly assessed on a weekly basis by self-evaluation of the patients themselves and by physicians. The results showed that the practices of care were different in the two units according to the specific goals and norms of each unit. A higher density of care was delivered at the Infectious and Tropical Diseases Unit. Symptoms assessed by both patients and physicians were underestimated by physicians in frequency and in intensity. In conclusion, an integrated approach including objective and subjective criteria should enable a better adjustment of the palliative and curative therapeutic strategies in advanced AIDS. These would concomitantly take into account the wishes of the patient and the goals regarding care in the unit where the patient is hospitalized.

  14. A comparison of postimplant dosimetry for {sup 103}Pd versus {sup 131}Cs seeds on a retrospective series of PBSI patients

    SciTech Connect

    Ravi, Ananth; Keller, Brian M.; Pignol, Jean-Philippe

    2011-11-15

    Purpose: Permanent breast seed implantation (PBSI) is an accelerated partial breast irradiation technique performed using stranded {sup 103}Pd radioactive seeds (average energy of 21 keV, 16.97 day half-life). Since 2004, {sup 131}Cs brachytherapy sources have become clinically available. The {sup 131}Cs radionuclide has a higher energy (average energy of 30 keV) and a shorter half-life (9.7 days) than {sup 103}Pd. The purpose of this study was to determine whether or not there are dosimetric benefits to using {sup 131}Cs brachytherapy seeds for PBSI. Methods: The prescribed dose for PBSI using {sup 103}Pd is 90 Gy, which was adjusted for {sup 131}Cs implants to account for the shorter half-life. A retrospective cohort of 30 patients, who have already undergone a {sup 103}Pd implant, was used for this study. The treatments were planned using the Variseed treatment planning system. The air kerma strength of the {sup 131}Cs seeds was adjusted in all preimplantation treatment plans so that the V{sub 100} (the volume within the target that receives 100% or more of the prescribed dose) were equivalent at time of implantation. Two month follow-up CT scans were available for all 30 patients and each patient was reevaluated using {sup 131}Cs seeds. The postimplant dosimetric parameters were compared using a two tailed t-test. Results: The prescribed dose for {sup 131}Cs was calculated to be 77 Gy; this dose would have the same biological effect as a PBSI implant with {sup 103}Pd of 90 Gy. The activities of the {sup 131}Cs sources were adjusted to an average of 2.2 {+-} 0.8 U for {sup 131}Cs compared to 2.5 {+-} 1.1 U for {sup 103}Pd in order to get an equivalent V{sub 100} as the {sup 103}Pd preimplants. While the use of {sup 131}Cs significantly reduces the preimplant V{sub 200} (the volume within the target that receives 200% or more of the prescribed dose) compared to {sup 103}Pd by 13.5 {+-} 9.0%, the reduction observed on the 2 month postimplant plan was 12.4 {+-} 5

  15. PD-1 expression on Melan-A-reactive T cells increases during progression to metastatic disease.

    PubMed

    Krönig, Holger; Julia Falchner, Kathrin; Odendahl, Marcus; Brackertz, Bettina; Conrad, Heinke; Muck, Dieter; Hein, Rüdiger; Blank, Christian; Peschel, Christian; Haller, Bernhard; Schulz, Stephan; Bernhard, Helga

    2012-05-15

    Programmed death 1 (PD-1) is known as an important factor for the development of tolerogenicity. This has been proven in chronic viral infections and different tumor models. To address the role of PD-1 and its ligand programmed death ligand 1 (PD-L1) in different stages of malignant melanoma, we investigated peripheral blood and tumor tissues in regard to overall survival (OS) and prognostic relevance. One hundred samples of peripheral blood mononuclear cells from HLA-A2(+) patients with malignant melanoma (Stages I-IV) were analyzed in seven color FACS combined with multimer analyses for the immunodominant epitope of Melan-A (peptide A2/Melan-A(p26-35mod) ). Corresponding formalin-fixed paraffin-embedded tissues of primary tumor and distant organ metastases from 37 cases were analyzed by immunohistochemistry for Melan-A, PD-L1 and PD-1 expression. Compared to the total CD8(+) T cell population, PD-1 expression by A2/Melan-A(+) CD8(+) T cells was over-represented in melanoma stages III and IV (p < 0.001). Although elevation of PD-1(+) Melan-A(+) CD8(+) T cells had no significant influence on OS, a positive correlation was observed between PD-L1 expression on melanoma cells and OS (p = 0.05). Correlation of advanced tumor stage with increased A2/Melan-A-multimer(+) PD-1(+) T cells in the peripheral blood suggest that blocking of PD-1 could have therapeutic potential in advanced stage melanoma.

  16. A Chimeric Switch-Receptor Targeting PD1 Augments the Efficacy of Second-Generation CAR T Cells in Advanced Solid Tumors.

    PubMed

    Liu, Xiaojun; Ranganathan, Raghuveer; Jiang, Shuguang; Fang, Chongyun; Sun, Jing; Kim, Soyeon; Newick, Kheng; Lo, Albert; June, Carl H; Zhao, Yangbing; Moon, Edmund K

    2016-03-15

    Chimeric antigen receptor (CAR)-modified adoptive T-cell therapy has been successfully applied to the treatment of hematologic malignancies, but faces many challenges in solid tumors. One major obstacle is the immune-suppressive effects induced in both naturally occurring and genetically modified tumor-infiltrating lymphocytes (TIL) by inhibitory receptors (IR), namely PD1. We hypothesized that interfering with PD1 signaling would augment CAR T-cell activity against solid tumors. To address this possibility, we introduced a genetically engineered switch receptor construct, comprising the truncated extracellular domain of PD1 and the transmembrane and cytoplasmic signaling domains of CD28, into CAR T cells. We tested the effect of this supplement, "PD1CD28," on human CAR T cells targeting aggressive models of human solid tumors expressing relevant tumor antigens. Treatment of mice bearing large, established solid tumors with PD1CD28 CAR T cells led to significant regression in tumor volume due to enhanced CAR TIL infiltrate, decreased susceptibility to tumor-induced hypofunction, and attenuation of IR expression compared with treatments with CAR T cells alone or PD1 antibodies. Taken together, our findings suggest that the application of PD1CD28 to boost CAR T-cell activity is efficacious against solid tumors via a variety of mechanisms, prompting clinical investigation of this potentially promising treatment modality.

  17. Febuxostat for hyperuricemia in patients with advanced chronic kidney disease.

    PubMed

    Akimoto, Tetsu; Morishita, Yoshiyuki; Ito, Chiharu; Iimura, Osamu; Tsunematsu, Sadao; Watanabe, Yuko; Kusano, Eiji; Nagata, Daisuke

    2014-01-01

    Febuxostat is a nonpurine xanthine oxidase (XO) inhibitor, which recently received marketing approval. However, information regarding the experience with this agent among advanced chronic kidney disease (CKD) patients is limited. In the current study, we investigated the effects of oral febuxostat in patients with advanced CKD with asymptomatic hyperuricemia. We demonstrated, for the first time, that not only the serum levels of uric acid (UA) but also those of 8-hydroxydeoxyguanosine, an oxidative stress marker, were significantly reduced after six months of febuxostat treatment, with no adverse events. These results encouraged us to pursue further investigations regarding the clinical impact of lowering the serum UA levels with febuxostat in advanced CKD patients in terms of concomitantly reducing oxidative stress via the blockade of XO. More detailed studies with a larger number of subjects and assessments of the effects of multiple factors affecting hyperuricemia, such as age, sex, and dietary habits, would shed light on the therapeutic challenges of treating asymptomatic hyperuricemia in patients with various stages of CKD. PMID:25210423

  18. Medial frontal ∼4-Hz activity in humans and rodents is attenuated in PD patients and in rodents with cortical dopamine depletion

    PubMed Central

    Parker, Krystal L.; Chen, Kuan-Hua; Kingyon, Johnathan R.; Cavanagh, James F.

    2015-01-01

    The temporal control of action is a highly conserved and critical mammalian behavior. Here, we investigate the neuronal basis of this process using an interval timing task. In rats and humans, instructional timing cues triggered spectral power across delta and theta bands (2–6 Hz) from the medial frontal cortex (MFC). Humans and rodents with dysfunctional dopamine have impaired interval timing, and we found that both humans with Parkinson's disease (PD) and rodents with local MFC dopamine depletion had attenuated delta and theta activity. In rodents, spectral activity in this range could functionally couple single MFC neurons involved in temporal processing. Without MFC dopamine, these neurons had less functional coupling with delta/theta activity and less temporal processing. Finally, in humans this 2- to 6-Hz activity was correlated with executive function in matched controls but not in PD patients. Collectively, these findings suggest that cue-evoked low-frequency rhythms could be a clinically important biomarker of PD that is translatable to rodent models, facilitating mechanistic inquiry and the development of neurophysiological biomarkers for human disease. PMID:26133799

  19. Investigation of morphometric variability of subthalamic nucleus, red nucleus, and substantia nigra in advanced Parkinson's disease patients using automatic segmentation and PCA-based analysis.

    PubMed

    Xiao, Yiming; Jannin, Pierre; D'Albis, Tiziano; Guizard, Nicolas; Haegelen, Claire; Lalys, Florent; Vérin, Marc; Collins, D Louis

    2014-09-01

    Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective surgical therapy to treat Parkinson's disease (PD). Conventional methods employ standard atlas coordinates to target the STN, which, along with the adjacent red nucleus (RN) and substantia nigra (SN), are not well visualized on conventional T1w MRIs. However, the positions and sizes of the nuclei may be more variable than the standard atlas, thus making the pre-surgical plans inaccurate. We investigated the morphometric variability of the STN, RN and SN by using label-fusion segmentation results from 3T high resolution T2w MRIs of 33 advanced PD patients. In addition to comparing the size and position measurements of the cohort to the Talairach atlas, principal component analysis (PCA) was performed to acquire more intuitive and detailed perspectives of the measured variability. Lastly, the potential correlation between the variability shown by PCA results and the clinical scores was explored.

  20. Long-term benefit of PD-L1 blockade in lung cancer associated with JAK3 activation

    PubMed Central

    Van Allen, Eliezer M.; Golay, Hadrien G.; Liu, Yan; Koyama, Shohei; Wong, Karrie; Taylor-Weiner, Amaro; Giannakis, Marios; Harden, Maegan; Rojas-Rudilla, Vanesa; Chevalier, Aaron; Thai, Tran; Lydon, Christine; Mach, Stacy; Wong, Joshua A.; Rabin, Alexandra R.; Helmkamp, Joshua; Sholl, Lynette; Carter, Scott L.; Oxnard, Geoffrey; Janne, Pasi; Getz, Gad; Lindeman, Neal; Hammerman, Peter S.; Garraway, Levi A.; Hodi, F. Stephen; Rodig, Scott; Dranoff, Glenn; Wong, Kwok-Kin; Barbie, David A.

    2015-01-01

    PD-1 immune checkpoint blockade occasionally results in durable clinical responses in advanced metastatic cancers. However, mechanism-based predictors of response to this immunotherapy remain incompletely characterized. We performed comprehensive genomic profiling on a tumor and germline sample from a patient with refractory lung adenocarcinoma who achieved marked long-term clinical benefit from anti-PD-L1 therapy. We discovered activating somatic and germline amino acid variants in JAK3 that promoted PD-L1 induction in lung cancer cells and in the tumor immune microenvironment. These findings suggest that genomic alterations that deregulate cytokine receptor signal transduction could contribute to PD-L1 activation and engagement of the PD-1 immune checkpoint in lung cancer. PMID:26014096

  1. [Vital prognosis in advanced cancer patients: a systematic literature review].

    PubMed

    Tavares, Teresa; Gonçalves, Edna

    2013-01-01

    Prognostication is a critical medical task for the adequacy of treatment and management of priorities and expectations of patients and families. In 2005, the European Association of Palliative Care (EAPC) published recommendations on the formulation of vital prognosis in advanced cancer patients. The aim of this study is to analyze the literature subsequent to this review and to update the presented recommendations. Using the same strategy of the EAPC group, we performed a systematic literature search in the electronic databases PubMed and Scopus, which included original studies in adults with advanced cancer, without tumor-directed treatment, with a median survival of less than 90 days. The articles were analyzed and classified according to the level of evidence by two independent reviewers. The 41 articles analyzed allowed to keep grade A recommendations for clinical estimation of survival and Palliative Prognostic score and now also for Palliative Prognostic Index, performance status, dyspnea, lymphopenia and lactate dehydrogenase. Recommendations regarding the use of C-reactive protein, leukocytosis, azotemia, hypoalbuminemia and male gender as predictors reached grade B. To formulate the vital prognosis and to communicate it properly to the patient and family are core competencies of physicians, particularly of those who deal with end of life patients. The clinical impression combined with scientific evidence allows us to estimate more accurately the survival, allowing prioritizing and managing more appropriately the existing resources.

  2. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy

    PubMed Central

    Taube, Janis M.; Klein, Alison; Brahmer, Julie R.; Xu, Haiying; Pan, Xiaoyu; Kim, Jung H.; Chen, Lieping; Pardoll, Drew M.; Topalian, Suzanne L.; Anders, Robert A.

    2014-01-01

    Purpose Immunomodulatory drugs differ in mechanism-of-action from directly cytotoxic cancer therapies. Identifying factors predicting clinical response could guide patient selection and therapeutic optimization. Experimental Design Patients (N=41) with melanoma, non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), colorectal carcinoma or castration-resistant prostate cancer were treated on an early phase trial of anti-PD-1 (nivolumab) at one institution and had evaluable pre-treatment tumor specimens. Immunoarchitectural features including PD-1, PD-L1, and PD-L2 expression, patterns of immune cell infiltration, and lymphocyte subpopulations, were assessed for interrelationships and potential correlations with clinical outcomes. Results Membranous (cell surface) PD-L1 expression by tumor cells and immune infiltrates varied significantly by tumor type and was most abundant in melanoma, NSCLC, and RCC. In the overall cohort, PD-L1 expression was geographically associated with infiltrating immune cells (p<0.001), although lymphocyte-rich regions were not always associated with PD-L1 expression. Expression of PD-L1 by tumor cells and immune infiltrates was significantly associated with expression of PD-1 on lymphocytes. PD-L2, the second ligand for PD-1, was associated with PD-L1 expression. Tumor cell PD-L1 expression correlated with objective response to anti-PD-1 therapy, when analyzing either the specimen obtained closest to therapy or the highest scoring sample among multiple biopsies from individual patients. These correlations were stronger than borderline associations of PD-1 expression or the presence of intratumoral immune cell infiltrates with response. Conclusions Tumor PD-L1 expression reflects an immune-active microenvironment and, while associated other immunosuppressive molecules including PD-1 and PD-L2, is the single factor most closely correlated with response to anti-PD-1 blockade. PMID:24714771

  3. PD-1 Pathway Inhibitors: Immuno-Oncology Agents for Restoring Antitumor Immune Responses.

    PubMed

    Medina, Patrick J; Adams, Val R

    2016-03-01

    Immune checkpoint inhibitors are designed to restore a patient's own antitumor immune response that has been suppressed during tumor development. The first monoclonal antibodies against the immune checkpoint programmed death 1 (PD-1) receptor, nivolumab and pembrolizumab, are now approved for clinical use. Both agents are indicated for the treatment of advanced melanoma, as well as for the treatment of metastatic non-small cell lung cancer (NSCLC). Nivolumab is also approved for the treatment of advanced renal cell carcinoma. In patients with melanoma, these agents result in objective response rates of ~25-40%, with durable responses lasting more than 2 years in some cases. Results from phase III trials have shown improved survival with nivolumab versus standard-of-care chemotherapy in both patients with advanced melanoma and those with advanced NSCLC. In patients with advanced melanoma, both PD-1 inhibitors (nivolumab and pembrolizumab) have shown improved survival versus ipilimumab. PD-1 inhibitors are associated with adverse events that have immune etiologies, with grade greater than 3 adverse events typically reported in 16% or less of patients. However, most immune-mediated adverse events (including grade 3-4 adverse events) can be managed by using published management algorithms without permanent discontinuation of the agent. As nivolumab and pembrolizumab enter the clinic, and with more PD-1 pathway agents in development for a range of tumor types, this review aims to provide pharmacists with a basic understanding of the role of PD-1 in modulating the immune system and their use in the cancer treatment. The most recent clinical efficacy and safety data are discussed, highlighting the response characteristics distinctive to immune checkpoint inhibitors, along with pharmacokinetic and pharmacodynamic data and cost considerations.

  4. Pulmonary Rehabilitation in Advanced Lung Cancer Patients During Chemotherapy.

    PubMed

    Jastrzębski, D; Maksymiak, M; Kostorz, S; Bezubka, B; Osmanska, I; Młynczak, T; Rutkowska, A; Baczek, Z; Ziora, D; Kozielski, J

    2015-01-01

    The aim of this study was to investigate the utility of pulmonary rehabilitation for improving of exercises efficiency, dyspnea, and quality of life of patients with lung cancer during chemotherapy. After the enrollment selection, the study included 20 patients with newly diagnosed advanced lung cancer and performance status 0-2. There were 12 patients randomly allocated to the pulmonary rehabilitation group and another 8 constituted the control group that did not undergo physical rehabilitation. Both groups of patients had continual cycles of chemotherapy. Data were analyzed before and after 8 weeks of physical rehabilitation, and before and after 8 weeks of observation without rehabilitation in controls. The inpatient rehabilitation program was based on exercise training with ski poles and respiratory muscle training. We found a tendency for enhanced mobility (6 Minute Walk Test: 527.3 ± 107.4 vs. 563.9 ±64.6 m; p > 0.05) and a significant increase in forced expired volume in 1 s (66.9 ± 13.2 vs. 78.4 ± 17.7 %predicted; p = 0.016), less dyspnea (p = 0.05), and a tendency for improvement in the general quality of life questionnaire after completion of pulmonary rehabilitation as compared with the control group. This report suggests that pulmonary rehabilitation in advanced lung cancer patients during chemotherapy is a beneficial intervention to reduce dyspnea and enhance the quality of life and mobility.

  5. Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy

    PubMed Central

    Johnson, Douglas B.; Estrada, Monica V.; Salgado, Roberto; Sanchez, Violeta; Doxie, Deon B.; Opalenik, Susan R.; Vilgelm, Anna E.; Feld, Emily; Johnson, Adam S.; Greenplate, Allison R.; Sanders, Melinda E.; Lovly, Christine M.; Frederick, Dennie T.; Kelley, Mark C.; Richmond, Ann; Irish, Jonathan M.; Shyr, Yu; Sullivan, Ryan J.; Puzanov, Igor; Sosman, Jeffrey A.; Balko, Justin M.

    2016-01-01

    Anti-PD-1 therapy yields objective clinical responses in 30–40% of advanced melanoma patients. Since most patients do not respond, predictive biomarkers to guide treatment selection are needed. We hypothesize that MHC-I/II expression is required for tumour antigen presentation and may predict anti-PD-1 therapy response. In this study, across 60 melanoma cell lines, we find bimodal expression patterns of MHC-II, while MHC-I expression was ubiquitous. A unique subset of melanomas are capable of expressing MHC-II under basal or IFNγ-stimulated conditions. Using pathway analysis, we show that MHC-II(+) cell lines demonstrate signatures of ‘PD-1 signalling', ‘allograft rejection' and ‘T-cell receptor signalling', among others. In two independent cohorts of anti-PD-1-treated melanoma patients, MHC-II positivity on tumour cells is associated with therapeutic response, progression-free and overall survival, as well as CD4+ and CD8+ tumour infiltrate. MHC-II+ tumours can be identified by melanoma-specific immunohistochemistry using commercially available antibodies for HLA-DR to improve anti-PD-1 patient selection. PMID:26822383

  6. Advanced Hemodynamic Management in Patients with Septic Shock

    PubMed Central

    Huber, Wolfgang; Nierhaus, Axel; Kluge, Stefan; Reuter, Daniel A.; Wagner, Julia Y.

    2016-01-01

    In patients with sepsis and septic shock, the hemodynamic management in both early and later phases of these “organ dysfunction syndromes” is a key therapeutic component. It needs, however, to be differentiated between “early goal-directed therapy” (EGDT) as proposed for the first 6 hours of emergency department treatment by Rivers et al. in 2001 and “hemodynamic management” using advanced hemodynamic monitoring in the intensive care unit (ICU). Recent large trials demonstrated that nowadays protocolized EGDT does not seem to be superior to “usual care” in terms of a reduction in mortality in emergency department patients with early identified septic shock who promptly receive antibiotic therapy and fluid resuscitation. “Hemodynamic management” comprises (a) making the diagnosis of septic shock as one differential diagnosis of circulatory shock, (b) assessing the hemodynamic status including the identification of therapeutic conflicts, and (c) guiding therapeutic interventions. We propose two algorithms for hemodynamic management using transpulmonary thermodilution-derived variables aiming to optimize the cardiocirculatory and pulmonary status in adult ICU patients with septic shock. The complexity and heterogeneity of patients with septic shock implies that individualized approaches for hemodynamic management are mandatory. Defining individual hemodynamic target values for patients with septic shock in different phases of the disease must be the focus of future studies. PMID:27703980

  7. Reaching Those Most in Need – A Call to Action for Advanced Parkinson’s Disease

    PubMed Central

    Agarwal, Shashank; Fleisher, Jori E

    2016-01-01

    Much of the clinical and research attention for Parkinson's Disease (PD) has focused on mild to moderate stages. As the disease advances, it can become difficult for patients to attend clinical visits. These patients are often lost to follow-up, and consequently, vanish from the pool of potential research subjects who could inform our management of this understudied population. We aim to increase awareness about this population and potential interventions to improve continuity of care and foster research in advanced PD.

  8. Efficacy of Anastrozole in a Consecutive Series of Advanced Breast Cancer Patients Treated with Multiple Prior Chemotherapies and Endocrine Agents: M. D. Anderson Cancer Center Experience.

    PubMed

    Knoche, A. Jolynn; Michaud, Laura Boehnke; Buzdar, Aman U.

    1999-05-01

    Anastrozole is a highly selective, nonsteroidal aromatase inhibitor approved by the U.S. Food and Drug Administration (FDA) in January 1996 for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. To date, information on anastrozole's use has been limited to breast cancer patients with minimal prior therapy. The purpose of this review was to determine, in clinical practice, the benefits of anastrozole in advanced breast cancer patients treated with multiple prior cytotoxic and endocrine therapies. This was a retrospective review of a consecutive series of 117 patients who received anastrozole after marketing in January 1996. As this was not a prospective study, rigorous response criteria could not be applied. Responses were categorized as improvement in disease (ID), stable disease (SD), or progressive disease (PD). One hundred eight patients were evaluable for response with a median age of 61 years and the number of prior therapies ranging from one to nine. Response, defined as improvement of disease or stable disease >/=8 weeks, was seen in 59% of patients. Patients with three or more prior endocrine therapies demonstrated a 61% response (ID + SD) and patients with ER-negative tumors demonstrated 50% response. Patients with prior aminoglutethamide therapy exhibited similar response rates to the overall group. One male patient received anastrozole without benefit. This data determines the activity of anastrozole even in heavily pretreated patients and suggests that patients who have tumors that are ER-negative may also benefit from anastrozole therapy. PMID:11348281

  9. [Molecular targeting agents for advanced or recurrent gastric cancer patients].

    PubMed

    Fuse, Nozomu

    2012-10-01

    The combination of fluoropyrimidine and platinum with or without epirubicin or docetaxel has been regarded as standard chemotherapy for advanced or recurrent gastric cancer patients. Recently, trastuzumab with conventional chemotherapy for human epidermal growth factor receptor(HER)2 positive gastric cancer patients was proved to be effective in terms of survival benefit and has become one of standard treatment options. Other molecular target agents, such as HER1, HER2, vascular endothelial growth factor, hepatocyte growth factor/c-Met, fibroblast growth factor and mammalian target of rapamycin inhibitors were and are being evaluated in clinical trials. However, no agents other than trastuzumab have shown clear survival benefit. The predictive biomarker seems to be necessary for developing new molecular targeting agents for gastric cancer with heterogeneity.

  10. Management of a patient with advanced BRAF-mutant melanoma.

    PubMed

    Ashworth, Michelle T; Daud, Adil

    2014-03-01

    A 49-year-old man initially diagnosed in 1995 with cutaneous melanoma presented to the authors' institution in 2009 with metastatic, BRAF V600E-mutant melanoma. His treatment course to date has included surgery, adjuvant radiotherapy, and interferon, metastasectomies, granulocyte-macrophage colony-stimulating factors, a clinical trial with the BRAF inhibitor vemurafenib (PLX-4032), clinical trial with combination BRAF plus MEK inhibition with vemurafenib plus GDC-0973, and combination targeted and immune therapy with vemurafenib plus the anti-CTLA4 antibody ipilimumab. This case report illustrates the long-term management of a patient with metastatic melanoma using targeted and immune therapy, evolution in treatment guidelines, next directions in research, and the critical role of clinical trials in advancement of patient care.

  11. Understanding Pd-Pd bond length variation in (PNP)Pd-Pd(PNP) dimers.

    PubMed

    Walensky, Justin R; Fafard, Claudia M; Guo, Chengyun; Brammell, Christina M; Foxman, Bruce M; Hall, Michael B; Ozerov, Oleg V

    2013-03-01

    Analysis of the structures of three (PNP)Pd-Pd(PNP) dimers [where PNP stands for anionic diarylamido/bis(phosphine) pincer ligands] has been carried out with the help of single-crystal X-ray diffractometry and density functional theory (DFT) calculations on isolated molecules. The three dimers under study possess analogous ancillary ligands; two of them differ only by an F versus Me substituent in a remote (five bonds away from Pd) position of the pincer ligand. Despite these close similarities, X-ray structural determinations revealed two distinct structural motifs: a highly symmetric molecule with a long Pd-Pd bond or a highly distorted molecule with Pd-Pd bonds ca. 0.14 Å shorter. DFT calculations on a series of (PNP)Pd-Pd(PNP) dimers (as molecules in the gas phase) confirmed the existence of these distinct minima for dimers carrying large isopropyl substituents on the P-donor atoms (as in the experimental structure). These minima are nearly isoergic conformers. Evidently, the electronically preferred symmetric structure for the dimer (with a square-planar environment about Pd and a linear N-Pd-Pd-N vector) is not sterically possible with the preferred Pd-Pd distance. Thus, the minima correspond to either a symmetric structure with a long Pd-Pd bond distance or a structure with a short Pd-Pd distance but with substantial distortions in the Pd coordination environment to alleviate steric conflict. This notion is supported by finding only a single minimum (symmetric and with short Pd-Pd bonds) for each of the dimers carrying smaller substituents (H or Me) on the P atoms, regardless of the remote substitution.

  12. Differential Patient-Caregiver Opinions of Treatment and Care For Advanced Lung Cancer Patients

    PubMed Central

    Zyzanski, Stephen J; Siminoff, Laura A

    2010-01-01

    This study examined the differences of opinion between cancer patients and caregivers with regard to treatment and care decisions. 184 advanced lung cancer patients and 171 primary caregivers were recruited as a convenience sample from clinics in Cleveland, Ohio. A telephone interview was conducted to collect data using a semi-structured questionnaire. Nonparametric tests and regression analysis were performed. The findings showed that patients and caregivers reported significant disagreement on three main issues: trade-off between treatment side effects and benefits; reporting treatment side effects to physicians, and hospice care. Caregivers were more concerned about patient’s quality of life and more willing to discuss hospice issues than were patients. Perceived family disagreement is associated with depression in both patients and caregivers. The study provided empirical evidence for patient-caregiver disagreement about treatment and care decisions and its significant adverse impact on both patients and caregivers. PMID:20137849

  13. [Advanced directives document and neurologist-patient relationship].

    PubMed

    Boada Rovira, M

    2004-12-01

    Perception of health and disease, pain and suffering, quality of life, personal relationships, privacy and intimacy, culture and social values, can now be stated in a written document, by way of a living will, giving legal legitimacy to each patient's way of being and understanding life, to be used when the subject cannot express it by him/herself. In this way, the patients will participate in the therapeutic process and will incorporate their desires and decisions through the Informed Consent and the Advanced Directives Document (ADD). Both documents translate and indicate how to treat and care for a patient who will progressively lose his/her cognitive faculties and others will decided for him/her, in the case of dementias. The basis of ADD is respect and promotion of the patient's autonomy, prolonging his/her right to decide in the stages in which he/she cannot do it. It consists in some instructions or orientations for the patient to be cared for in a certain way, according to his/her will. To this effect, a representative will be named who will act in the subject's name and who will help to interpret and make decisions when the patient cannot. Specifically, in Alzheimer's disease, ADD allows the patient to decide, in full lucidity, freedom and autonomy, how to live a progressive and irreversible disease. Explicit mention can be made to the will of making his/her disease known publically or not, the care of its aspect, privacy, type of care, whether institutionalized or home care, limitation of visits, treatment intensity and prolongation, palliative cares, donation of biological samples, participation in drug clinical trials. PMID:15719290

  14. Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy.

    PubMed

    Ma, Weijie; Gilligan, Barbara M; Yuan, Jianda; Li, Tianhong

    2016-05-27

    Modulating immune inhibitory pathways has been a major recent breakthrough in cancer treatment. Checkpoint blockade antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programed cell-death protein 1 (PD-1) have demonstrated acceptable toxicity, promising clinical responses, durable disease control, and improved survival in some patients with advanced melanoma, non-small cell lung cancer (NSCLC), and other tumor types. About 20 % of advanced NSCLC patients and 30 % of advanced melanoma patients experience tumor responses from checkpoint blockade monotherapy, with better clinical responses seen with the combination of anti-PD-1 and anti-CTLA-4 antibodies. Given the power of these new therapies, it is important to understand the complex and dynamic nature of host immune responses and the regulation of additional molecules in the tumor microenvironment and normal organs in response to the checkpoint blockade therapies. In this era of precision oncology, there remains a largely unmet need to identify the patients who are most likely to benefit from immunotherapy, to optimize the monitoring assays for tumor-specific immune responses, to develop strategies to improve clinical efficacy, and to identify biomarkers so that immune-related adverse events can be avoided. At this time, PD-L1 immunohistochemistry (IHC) staining using 22C3 antibody is the only FDA-approved companion diagnostic for patients with NSCLC-treated pembrolizumab, but more are expected to come to market. We here summarize the current knowledge, clinical efficacy, potential immune biomarkers, and associated assays for immune checkpoint blockade therapies in advanced solid tumors.

  15. Ifosfamide plus etoposide combined with regional hyperthermia in patients with locally advanced sarcomas: a phase II study.

    PubMed

    Issels, R D; Prenninger, S W; Nagele, A; Boehm, E; Sauer, H; Jauch, K W; Denecke, H; Berger, H; Peter, K; Wilmanns, W

    1990-11-01

    From July 1986 to July 1989, 40 patients (92% pretreated) with deep-seated, advanced soft tissue sarcomas (STS, 25 patients), Ewing's sarcomas (ES, eight patients), osteosarcomas (OS, three patients) and chondrosarcomas (ChS, four patients) were treated at the University of Munich in a protocol involving regional hyperthermia (RHT) combined with ifosfamide plus etoposide. A total of 265 RHT treatments (mean, 6.6 RHT per patient) were applied including 33 pelvic, four extremity, and three abdominal sites. The mean tumor volume was 537 cc (range, 50 to 2,980 cc). For systemic chemotherapy, all patients received ifosfamide (1.5 g/m2, days 1 to 5), etoposide (100 mg/m2, days 1, 3, and 5), and mesna (300 mg/m2 x 4, days 1 to 5) with RHT given only on days 1 and 5 in repeated cycles every 4 weeks. Acute toxicity consisted primarily of pain (57%) combined with local discomfort within the annular phased array applicator (AA) of the BSD hyperthermia system (BSD Medical Corp, Salt Lake City, UT). The average maximum systemic temperature was 37.4 +/- 0.5 degrees C, and there was no indication of enhanced bone marrow toxicity due to the addition of RHT to the systemic chemotherapy. Detailed thermal mapping by invasive thermometry was performed in all patients. In 38 assessable patients, the overall objective response rate was 37%: six complete responses (CRs), four partial responses (PRs), and four favorable histologic responses (FHRs) (95% confidence limits, 22% to 54%). Complete responders are alive and disease-free at 40, 35, 23, 19, 19, and 8 months. Of patients with PR and FHR, two died from metastatic disease after 4 and 17 months and one died from other disease after 27 months. The remaining five patients are stable at 37, 25, 21, 13, and 8 months. Eleven patients showed no change (NC), and 13 patients showed local tumor progression (PD). The mean observation time for all patients was 11.6 months. The time-averaged temperatures (Ts) of all RHT treatments calculated as

  16. Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers

    PubMed Central

    Carbognin, Luisa; Pilotto, Sara; Milella, Michele; Vaccaro, Vanja; Brunelli, Matteo; Caliò, Anna; Cuppone, Federica; Sperduti, Isabella; Giannarelli, Diana; Chilosi, Marco; Bronte, Vincenzo; Scarpa, Aldo

    2015-01-01

    Background The potential predictive role of programmed death-ligand-1 (PD-L1) expression on tumor cells in the context of solid tumor treated with checkpoint inhibitors targeting the PD-1 pathway represents an issue for clinical research. Methods Overall response rate (ORR) was extracted from phase I-III trials investigating nivolumab, pembrolizumab and MPDL3280A for advanced melanoma, non-small cell lung cancer (NSCLC) and genitourinary cancer, and cumulated by adopting a fixed and random-effect model with 95% confidence interval (CI). Interaction test according to tumor PD-L1 was accomplished. A sensitivity analysis according to adopted drug, tumor type, PD-L1 cut-off and treatment line was performed. Results Twenty trials (1,475 patients) were identified. A significant interaction (p<0.0001) according to tumor PD-L1 expression was found in the overall sample with an ORR of 34.1% (95% CI 27.6-41.3%) in the PD-L1 positive and 19.9% (95% CI 15.4-25.3%) in the PD-L1 negative population. ORR was significantly higher in PD-L1 positive in comparison to PD-L1 negative patients for nivolumab and pembrolizumab, with an absolute difference of 16.4% and 19.5%, respectively. A significant difference in activity of 22.8% and 8.7% according to PD-L1 was found for melanoma and NSCLC, respectively, with no significant difference for genitourinary cancer. Conclusion Overall, the three antibodies provide a significant differential effect in terms of activity according to PD-L1 expression on tumor cells. The predictive value of PD-L1 on tumor cells seems to be more robust for anti-PD-1 antibody (nivolumab and pembrolizumab), and in the context of advanced melanoma and NSCLC. PMID:26086854

  17. Peritoneal ultrafiltration in patients with advanced decompensated heart failure.

    PubMed

    Iadarola, Gian Maria; Lusardi, Paola; La Milia, Vincenzo; Amici, Gianpaolo; Santarelli, Stefano; Virga, Giovambattista; Basile, Carlo; Bertoli, Silvio; Bonofiglio, Renzo; Del Rosso, Goffredo; Feriani, Mariano; Galli, Emilio; Gallieni, Maurizio; Gambaro, Giovanni; Sandrini, Massimo; Sisca, Sergio; Cancarini, Giovanni

    2013-01-01

    The aim of the Best Practice guidelines on peritoneal ultrafiltration (UF) in patients with treatment-resistant advanced decompensated heart failure (TR-AHDF) is to achieve a common approach to the management of decompensated heart failure in those situations in which all conventional treatment options have been unsuccessful, and to stimulate a closer cooperation between nephrologists and cardiologists. The standardization of the case series of different centers would allow a better definition of the results published in the literature, without which they are nothing more than anecdotes. TR-AHDF is characterized by the persistence of severe symptoms even when all possible pharmacological and surgical options have been exhausted. These patients are often treated with methods that allow extracorporeal UF - slow continuous ultrafiltration (SCUF) and continuous renal replacement therapy (CRRT) - which have to be performed in hospital facilities. Peritoneal ultrafiltration (PUF) can be considered a treatment option in patients with TR-AHDF when, despite the fact that all treatment options have been used, patients meet the following criteria: • stage D decompensated heart failure (ACC/AHA classification); • INTERMACS level 4 decompensated heart failure; • INTERMACS frequent flyer profile; • chronic renal failure (estimated glomerular filtration rate <50 ml/min per 1.73 m2: KDOQI classification stage 3 chronic kidney disease); • no obvious contraindications to peritoneal UF. PUF treatment modes are derived from the treatment regimens proposed by various authors to obtain systemic UF in patients with severe decompensated heart failure, using manual and automated incremental peritoneal dialysis involving various glucose concentrations in addition to the single icodextrin exchange. These guidelines also identify a minimum set of tests and procedures for the follow-up phase, to be supplemented, according to the center's resources and policy, with other tests that

  18. Urinary Stone Disease: Advancing Knowledge, Patient Care, and Population Health.

    PubMed

    Scales, Charles D; Tasian, Gregory E; Schwaderer, Andrew L; Goldfarb, David S; Star, Robert A; Kirkali, Ziya

    2016-07-01

    Expanding epidemiologic and physiologic data suggest that urinary stone disease is best conceptualized as a chronic metabolic condition punctuated by symptomatic, preventable stone events. These acute events herald substantial future chronic morbidity, including decreased bone mineral density, cardiovascular disease, and CKD. Urinary stone disease imposes a large and growing public health burden. In the United States, 1 in 11 individuals will experience a urinary stone in their lifetime. Given this high incidence and prevalence, urinary stone disease is one of the most expensive urologic conditions, with health care charges exceeding $10 billion annually. Patient care focuses on management of symptomatic stones rather than prevention; after three decades of innovation, procedural interventions are almost exclusively minimally invasive or noninvasive, and mortality is rare. Despite these advances, the prevalence of stone disease has nearly doubled over the past 15 years, likely secondary to dietary and health trends. The NIDDK recently convened a symposium to assess knowledge and treatment gaps to inform future urinary stone disease research. Reducing the public health burden of urinary stone disease will require key advances in understanding environmental, genetic, and other individual disease determinants; improving secondary prevention; and optimal population health strategies in an increasingly cost-conscious care environment. PMID:26964844

  19. Integrative and complementary therapies for patients with advanced cancer.

    PubMed

    Marchand, Lucille

    2014-07-01

    In integrative medicine, well-being is emphasized, and in palliative care, quality of life (QOL) is a similar concept or goal. Both can occur despite advanced cancer. Integrative medicine serves to combine the best of alternative, complementary and conventional therapies to optimize well-being and QOL, whether or not a person is at the end of their life. When integrative medicine is combined with palliative care modalities, the toolbox to provide symptom control and well-being or QOL is increased or broadened. Palliative care and integrative medicine are best provided early in the trajectory of illness such as cancer, and increase in amount as the illness progresses toward end of life. In cancer care, symptoms of the cancer, as well as symptoms produced by cancer therapies, are addressed with conventional and integrative therapies. Goals of care change as the disease progresses, and a patient's unique situation creates a different balance of integrative and conventional therapies. Integrative therapies such as music, aromatherapy, and massage might appeal to more patients than more specific, less common integrative therapies that might be more expensive, or seem more unusual such as Ayurvedic medicine and energy modalities. Each person may be drawn to different integrative modalities depending on factors such as cultural traditions, beliefs, lifestyle, internet information, advice from family and friends, books, etc. This review focuses on how integrative and complementary modalities can be included in comprehensive palliative care for patients with advanced malignancies. Nutrition and movement, often neglected in conventional treatment strategies, will also be included in the larger context of integrative and palliative modalities. Both conventional and integrative modalities in palliative care help patients live with empowerment, hope, and well-being no matter how long their lives last. A comprehensive review of all integrative and complementary therapies is

  20. Early Clinical Response after 2 Weeks of Sorafenib Therapy Predicts Outcomes and Anti-Tumor Response in Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    Kuzuya, Teiji; Ishigami, Masatoshi; Ishizu, Yoji; Honda, Takashi; Hayashi, Kazuhiko; Katano, Yoshiaki; Hirooka, Yoshiki; Ishikawa, Tetsuya; Nakano, Isao; Goto, Hidemi

    2015-01-01

    Background & Aims We evaluated the relationship between the early clinical response after 2 weeks of sorafenib therapy and the outcomes and anti-tumor response in patients with advanced hepatocellular carcinoma. Methods Fifty-seven patients who had intrahepatic hypervascular hepatocellular carcinoma and Child-Pugh (CP) class A disease at baseline were enrolled in this prospective, multicenter, observational, non-interventional study. As an early clinical response after 2 weeks of sorafenib therapy, changes in intra-tumor blood flow on contrast-enhanced computed tomography (CE-CT), alpha-fetoprotein (AFP) levels, and remnant liver function were investigated. Results After 2 weeks of sorafenib therapy, there were 26 patients (45.6%) without disappearance of arterial tumor enhancement on CE-CT, 15 patients (26.3%) with an AFP ratio of >1.2, and seven patients (12.3%) with two or more increments in the CP score. Multivariate analysis showed that the absence of disappearance of arterial tumor enhancement on CE-CT, AFP ratio of >1.2, and two or more increments in the CP score after 2 weeks of sorafenib therapy were significant and independent predictors of worse survival. Upon scoring these three variables as "poor prognostic factors", patients with poor prognostic score 4, 3 or 2 (n = 17) had significantly worse outcomes and a significantly higher progressive disease (PD) rate based on modified Response Evaluation Criteria in Solid Tumors at 6 weeks after sorafenib therapy than those with poor prognostic score 1 or 0 (n = 40) (median overall survival: 194 days vs. 378 days; p = 0.0010, PD rate: 70.6% vs. 20.0%; p = 0.0003, respectively). Conclusions Changes in intra-tumor blood flow on CE-CT, AFP levels, and remnant liver function after 2 weeks of sorafenib therapy may be useful for predicting the outcomes and anti-tumor response to sorafenib in patients with advanced hepatocellular carcinoma. PMID:26421430

  1. miR-424(322) reverses chemoresistance via T-cell immune response activation by blocking the PD-L1 immune checkpoint

    PubMed Central

    Xu, Shaohua; Tao, Zhen; Hai, Bo; Liang, Huagen; Shi, Ying; Wang, Tao; Song, Wen; Chen, Yong; OuYang, Jun; Chen, Jinhong; Kong, Fanfei; Dong, Yishan; Jiang, Shi-Wen; Li, Weiyong; Wang, Ping; Yuan, Zhiyong; Wan, Xiaoping; Wang, Chenguang; Li, Wencheng; Zhang, Xiaoping; Chen, Ke

    2016-01-01

    Immune checkpoint blockade of the inhibitory immune receptors PD-L1, PD-1 and CTLA-4 has emerged as a successful treatment strategy for several advanced cancers. Here we demonstrate that miR-424(322) regulates the PD-L1/PD-1 and CD80/CTLA-4 pathways in chemoresistant ovarian cancer. miR-424(322) is inversely correlated with PD-L1, PD-1, CD80 and CTLA-4 expression. High levels of miR-424(322) in the tumours are positively correlated with the progression-free survival of ovarian cancer patients. Mechanistic investigations demonstrated that miR-424(322) inhibited PD-L1 and CD80 expression through direct binding to the 3′-untranslated region. Restoration of miR-424(322) expression reverses chemoresistance, which is accompanied by blockage of the PD-L1 immune checkpoint. The synergistic effect of chemotherapy and immunotherapy is associated with the proliferation of functional cytotoxic CD8+ T cells and the inhibition of myeloid-derived suppressive cells and regulatory T cells. Collectively, our data suggest a biological and functional interaction between PD-L1 and chemoresistance through the microRNA regulatory cascade. PMID:27147225

  2. The changing hope trajectory in patients with advanced-stage cancer: a nursing perspective.

    PubMed

    Sanders, Judith Brown; Seda, Julie S; Kardinal, Carl G

    2012-06-01

    As patients with advanced-stage cancer move from the initial diagnosis through treatment, remission, recurrence, and advanced-stage disease, the hope trajectory undergoes a dynamic transformation. By identifying the hope trajectory, nurses can help patients focus on obtainable hope objects while balancing the need to present a realistic prognosis. This, in turn, may help patients find meaning and purpose in advanced-stage cancer and facilitate realistic hope when faced with a life-threatening illness.

  3. Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure).

    PubMed

    Kim, J M; Chen, D S

    2016-08-01

    The emergence of programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1)-targeted therapy has demonstrated the importance of the PD-L1 : PD-1 interaction in inhibiting anticancer T-cell immunity in multiple human cancers, generating durable responses and extended overall survival. However, not all patients treated with PD-L1/PD-1-targeted therapy experience tumor shrinkage, durable responses, or prolonged survival. To extend such benefits to more cancer patients, it is necessary to understand why some patients experience primary or secondary immune escape, in which the immune response is incapable of eradicating all cancer cells. Understanding immune escape from PD-L1/PD-1-targeted therapy will be important to the development of rational immune-combination therapy and predictive diagnostics and to the identification of novel immune targets. Factors that likely relate to immune escape include the lack of strong cancer antigens or epitopes recognized by T cells, minimal activation of cancer-specific T cells, poor infiltration of T cells into tumors, downregulation of the major histocompatibility complex on cancer cells, and immunosuppressive factors and cells in the tumor microenvironment. Precisely identifying and understanding these mechanisms of immune escape in individual cancer patients will allow for personalized cancer immunotherapy, in which monotherapy and combination immunotherapy are chosen based on the presence of specific immune biology. This approach may enable treatment with immunotherapy without inducing immune escape, resulting in a larger proportion of patients obtaining clinical benefit.

  4. Advances in the treatment of cognitive impairment in Parkinson's disease.

    PubMed

    Goldman, Jennifer G; Weintraub, Daniel

    2015-09-15

    Cognitive impairment in Parkinson's disease (PD) is a frequent complication, with significant interindividual variability in clinical symptoms, severity, timing, and neural substrates. Recent studies have focused not only on understanding PD dementia, but also mild cognitive impairment in PD, which may represent a prodromal stage for dementia. In recent years, there have been important advances regarding clinical characterizations, definitions, associated biomarkers, and risk factors for both mild cognitive impairment in PD and PD dementia. However, there is a paucity of effective therapies for cognitive impairment in PD, whether for mild symptoms or for moderate to severe dementia. At present, only rivastigmine is U.S. Food and Drug Administration approved for PD dementia, an indication received nearly a decade ago. Given the frequency of PD cognitive impairment and its substantial impact on both patients and families, the lack of available and effective treatments represents a striking gap in the field, especially when compared to the large number of available therapies for PD motor symptoms and complications. Improved symptomatic therapies, as well as potential disease-modifying agents, for PD cognitive impairment are needed. Most therapeutic trials for PD dementia and mild cognitive impairment in PD have focused on drugs developed for and tested in Alzheimer's disease, such as cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist, memantine, though recent and ongoing trials examine the effects of pharmacological agents affecting other neurotransmitters, as well as nonpharmacological therapies, including mental and physical exercise and neurostimulation. This review summarizes the design and outcomes of trials for PD cognitive impairment published since 2013 and highlights future therapeutic research opportunities and challenges.

  5. Using Adult Learning Concepts To Assist Patients in Completing Advance Directives.

    ERIC Educational Resources Information Center

    Meyer, Rose Mary

    2000-01-01

    Advance directives that enable individuals to control their health care are underused due to lack of patient knowledge. Nurses can teach patients about them using adult learning principles, transformation theory, and skills for learning how to learn. (SK)

  6. Intraoperative Hyperthermic Intraperitoneal Chemotherapy in Patients With Advanced Ovarian Cancer.

    PubMed

    Oseledchyk, Anton; Zivanovic, Oliver

    2015-09-01

    Ovarian cancer, because it is largely confined to the peritoneal cavity, has a unique tumor biology and metastatic spread pattern. Its metastatic potential comes from detached tumor cells in the peritoneal cavity that re-attach to the mesothelial lining of the peritoneal surface. It is proposed that these micrometastases without neovasculature, as well as floating malignant cells, are drivers of early recurrence, since they can be neither resected nor adequately treated by systemic chemotherapy. This represents the major rationale for local treatment by means of postoperative intraperitoneal (IP) chemotherapy, which is the standard of care in the United States in patients with advanced-stage ovarian cancer who have minimal residual disease following cytoreductive surgery. An alternative loco-regional treatment strategy is the "HIPEC" procedure--hyperthermic IP chemoperfusion that is performed during the operation immediately following completion of gross tumor resection, and which provides improved tissue penetration and distribution of the chemotherapeutics. However, prospective data are limited and an outcomes benefit has yet to be shown. Here we discuss the advantages and pitfalls of HIPEC, as well as current data and ongoing prospective trials. PMID:26384807

  7. [Technological advances and micro-inflammation in dialysis patients].

    PubMed

    Ferro, Giuseppe; Ravaglia, Fiammetta; Ferrari, Elisa; Romoli, Elena; Michelassi, Stefano; Caiani, David; Pizzarelli, Francesco

    2015-01-01

    As currently performed, on line hemodiafiltration reduces, but does not normalize, the micro-inflammation of uremic patients. Recent technological advances make it possible to further reduce the inflammation connected to the dialysis treatment. 
Short bacterial DNA fragments are pro-inflammatory and can be detected in the dialysis fluids. However, their determination is not currently within normal controls of the quality of the dialysate. The scenario may change once the analysis of these fragments yields reliable, inexpensive, quick and easy to evaluate the results. At variance with standard bicarbonate dialysate, Citrate dialysate induces far less inflammation both for the well-known anti-inflammatory effect of such buffer and also because it is completely acetate free, e.g. a definitely pro-inflammatory buffer. However, the extensive use of citrate dialysate in chronic dialysis is prevented because of concerns about its potential calcium lowering effect. In our view, high convective exchange on line hemodiafiltration performed with dialysate, whose sterility and a-pirogenicity is guaranteed by increasingly sophisticated controls and with citrate buffer whose safety is certified, can serve as the gold standard of dialysis treatments in future.

  8. Distinguishing Symptoms of Grief and Depression in a Cohort of Advanced Cancer Patients

    ERIC Educational Resources Information Center

    Jacobsen, Juliet C.; Zhang, Baohui; Block, Susan D.; Maciejewski, Paul K.; Prigerson, Holly G.

    2010-01-01

    Several studies have shown that the symptoms of grief are different from symptoms of depression among bereaved family members. This study is an attempt to replicate this finding among advanced cancer patients and examine clinical correlates of patient grief and depression. Analyses were conducted on data from interviews with 123 advanced cancer…

  9. Evaluation of Instrumental Activities of Daily Living in Greek Patients with Advanced Cancer

    ERIC Educational Resources Information Center

    Mystakidou, Kyriaki; Parpa, Efi; Tsilika, Eleni; Panagiotoua, Irene; Roumeliotou, Anna; Symeonidi, Matina; Galanos, Antonis; Kouvaris, Ioannis

    2013-01-01

    Translation of the instrumental activities of daily living (IADL) was carried out and its psychometric properties were assessed in a Greek sample of patients with advanced cancer. The scale was translated with the forward-backward procedure into the Greek language. It was initially administered to 136 advanced cancer patients. To assess…

  10. Anti-PD-1 Inhibitor-Related Pneumonitis in Non-Small Cell Lung Cancer.

    PubMed

    Nishino, Mizuki; Chambers, Emily S; Chong, Curtis R; Ramaiya, Nikhil H; Gray, Stacy W; Marcoux, J Paul; Hatabu, Hiroto; Jänne, Pasi A; Hodi, F Stephen; Awad, Mark M

    2016-04-01

    The recent approval of two PD-1 inhibitors for the treatment of non-small cell lung cancer (NSCLC) has rapidly led to the widespread use of these agents in oncology practices. Pneumonitis has been recognized as a potentially life-threatening adverse event among NSCLC patients treated with PD-1 inhibitors; however, the detailed clinical and radiographic manifestations of this entity remain to be described. We report on two cases of anti-PD-1 pneumonitis in advanced NSCLC patients treated with nivolumab after its FDA approval. Both patients presented with ground-glass and reticular opacities and consolidations in a peripheral distribution on CT, demonstrating a radiographic pattern of cryptogenic organizing pneumonia. Consolidations were extensive and rapidly developed within 8 weeks of therapy in both cases. Both patients were treated with corticosteroids with subsequent improvement of respiratory symptoms and radiographic findings. One patient experienced recurrent pneumonitis after completing corticosteroid taper, or a "pneumonitis flare," in the absence of nivolumab retreatment, with subsequent improvement upon corticosteroid readministration. With the increasing use of immune checkpoint inhibitors in a growing number of tumor types, awareness of the radiographic and clinical manifestations of PD-1 inhibitor-related pneumonitis will be critical for the prompt diagnosis and management of this potentially serious adverse event. PMID:26865455

  11. Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma.

    PubMed

    Hugo, Willy; Zaretsky, Jesse M; Sun, Lu; Song, Chunying; Moreno, Blanca Homet; Hu-Lieskovan, Siwen; Berent-Maoz, Beata; Pang, Jia; Chmielowski, Bartosz; Cherry, Grace; Seja, Elizabeth; Lomeli, Shirley; Kong, Xiangju; Kelley, Mark C; Sosman, Jeffrey A; Johnson, Douglas B; Ribas, Antoni; Lo, Roger S

    2016-03-24

    PD-1 immune checkpoint blockade provides significant clinical benefits for melanoma patients. We analyzed the somatic mutanomes and transcriptomes of pretreatment melanoma biopsies to identify factors that may influence innate sensitivity or resistance to anti-PD-1 therapy. We find that overall high mutational loads associate with improved survival, and tumors from responding patients are enriched for mutations in the DNA repair gene BRCA2. Innately resistant tumors display a transcriptional signature (referred to as the IPRES, or innate anti-PD-1 resistance), indicating concurrent up-expression of genes involved in the regulation of mesenchymal transition, cell adhesion, extracellular matrix remodeling, angiogenesis, and wound healing. Notably, mitogen-activated protein kinase (MAPK)-targeted therapy (MAPK inhibitor) induces similar signatures in melanoma, suggesting that a non-genomic form of MAPK inhibitor resistance mediates cross-resistance to anti-PD-1 therapy. Validation of the IPRES in other independent tumor cohorts defines a transcriptomic subset across distinct types of advanced cancer. These findings suggest that attenuating the biological processes that underlie IPRES may improve anti-PD-1 response in melanoma and other cancer types.

  12. Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma.

    PubMed

    Hugo, Willy; Zaretsky, Jesse M; Sun, Lu; Song, Chunying; Moreno, Blanca Homet; Hu-Lieskovan, Siwen; Berent-Maoz, Beata; Pang, Jia; Chmielowski, Bartosz; Cherry, Grace; Seja, Elizabeth; Lomeli, Shirley; Kong, Xiangju; Kelley, Mark C; Sosman, Jeffrey A; Johnson, Douglas B; Ribas, Antoni; Lo, Roger S

    2016-03-24

    PD-1 immune checkpoint blockade provides significant clinical benefits for melanoma patients. We analyzed the somatic mutanomes and transcriptomes of pretreatment melanoma biopsies to identify factors that may influence innate sensitivity or resistance to anti-PD-1 therapy. We find that overall high mutational loads associate with improved survival, and tumors from responding patients are enriched for mutations in the DNA repair gene BRCA2. Innately resistant tumors display a transcriptional signature (referred to as the IPRES, or innate anti-PD-1 resistance), indicating concurrent up-expression of genes involved in the regulation of mesenchymal transition, cell adhesion, extracellular matrix remodeling, angiogenesis, and wound healing. Notably, mitogen-activated protein kinase (MAPK)-targeted therapy (MAPK inhibitor) induces similar signatures in melanoma, suggesting that a non-genomic form of MAPK inhibitor resistance mediates cross-resistance to anti-PD-1 therapy. Validation of the IPRES in other independent tumor cohorts defines a transcriptomic subset across distinct types of advanced cancer. These findings suggest that attenuating the biological processes that underlie IPRES may improve anti-PD-1 response in melanoma and other cancer types. PMID:26997480

  13. 102Pd(n, {gamma}) Cross Section Measurement Using DANCE

    SciTech Connect

    Hatarik, R.; Alpizar-Vicente, A. M.; Bredeweg, T. A.; Esch, E.-I.; Haight, R. C.; O'Donnell, J. M.; Reifarth, R.; Rundberg, R. S.; Ullmann, J. L.; Vieira, D. J.; Wouters, J. M.; Greife, U.

    2006-03-13

    The neutron capture cross section of the proton rich nucleus 102Pd was measured with the Detector for Advanced Neutron Capture Experiments (DANCE) at the Los Alamos Neutron Science Center. The target was a 2 mg Pd foil with 78% enriched 102Pd. It was held by a 0.9 {mu}m thick Mylar bag which was selected after comparing different thicknesses of Kapton and Mylar for their scattering background. To identify the contribution of the other Pd isotopes the data of a natural Pd sample was compared to the data of the 102Pd enriched sample. A 12C sample was used to determine the scattering background. The 102Pd(n, {gamma}) rate is of importance for the p-process nucleosynthesis.

  14. Elevated Cellular PD1/PD-L1 Expression Confers Acquired Resistance to Cisplatin in Small Cell Lung Cancer Cells.

    PubMed

    Yan, Fei; Pang, Jiuxia; Peng, Yong; Molina, Julian R; Yang, Ping; Liu, Shujun

    2016-01-01

    Although small cell lung cancer (SCLC) is highly responsive to chemotherapies (e.g., cisplatin-etoposide doublet), virtually almost all responsive SCLC patients experience disease recurrence characterized by drug resistance. The mechanisms underlying cisplatin resistance remain elusive. Here we report that cell-intrinsic expression of PD1 and PD-L1, two immune checkpoints, is required for sustained expansion of SCLC cells under cisplatin selection. Indeed, PD1 and PD-L1 were expressed at a higher level in lung cancer cell lines, tumor tissues, and importantly, in SCLC cells resistant to cisplatin (H69R, H82R), when compared to respective controls. Genetic abrogation of PD1 and PD-L1 in H69R and H82R cells decreased their proliferation rate, and restored their sensitivity to cisplatin. Mechanistically, PD-L1 upregulation in H69R and H82R cells was attributed to the overexpression of DNA methyltransferase 1 (DNMT1) or receptor tyrosine kinase KIT, as knockdown of DNMT1 or KIT in H69R and H82R cells led to PD-L1 downregulation. Consequently, combined knockdown of PD-L1 with KIT or DNMT1 resulted in more pronounced inhibition of H69R and H82R cell growth. Thus, cell intrinsic PD1/PD-L1 signaling may be a predictor for poor efficacy of cisplatin treatment, and targeting the cellular PD1/PD-L1 axis may improve chemosensitization of aggressive SCLC.

  15. The Ontario Prehospital Advanced Life Support (OPALS) Study: rationale and methodology for cardiac arrest patients.

    PubMed

    Stiell, I G; Wells, G A; Spaite, D W; Lyver, M B; Munkley, D P; Field, B J; Dagnone, E; Maloney, J P; Jones, G R; Luinstra, L G; Jermyn, B D; Ward, R; DeMaio, V J

    1998-08-01

    The Ontario Prehospital Advanced Life Support Study represents the largest prehospital study yet conducted, worldwide. This study will involve more than 25,000 cardiac arrest, trauma, and critically ill patients over an 8-year period. The study will evaluate the incremental benefit of rapid defibrillation and prehospital Advanced Cardiac Life Support measures for cardiac arrest survival and the benefit of Advanced Life Support for patients with traumatic injuries and other critically ill prehospital patients. This article describes the OPALS study with regard to the rationale and methodology for cardiac arrest patients.

  16. Quality Nursing Care for Hospitalized Patients with Advanced Illness: Concept Development

    PubMed Central

    Izumi, Shigeko; Baggs, Judith G.; Knafl, Kathleen A.

    2011-01-01

    The quality of nursing care as perceived by hospitalized patients with advanced illness has not been examined. A concept of quality nursing care for this population was developed by integrating the literature on constructs defining quality nursing care with empirical findings from interviews of 16 patients with advanced illness. Quality nursing care was characterized as competence and personal caring supported by professionalism and delivered with an appropriate demeanor. Although the attributes of competence, caring, professionalism, and demeanor were identified as common components of quality care across various patient populations, the caring domain increased in importance when patients with advanced illness perceived themselves as vulnerable. Assessment of quality nursing care for patients with advanced illness needs to include measures of patient perceptions of vulnerability. PMID:20572095

  17. Anti–PD-1/PD-L1 therapy of human cancer: past, present, and future

    PubMed Central

    Chen, Lieping; Han, Xue

    2015-01-01

    Major progress has been made toward our understanding of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway (referred to as the PD pathway). mAbs are already being used to block the PD pathway to treat human cancers (anti-PD therapy), especially advanced solid tumors. This therapy is based on principles that were discovered through basic research more than a decade ago, but the great potential of this pathway to treat a broad spectrum of advanced human cancers is just now becoming apparent. In this Review, we will briefly review the history and development of anti-PD therapy, from the original benchwork to the most up-to-date clinical results. We will then focus the discussion on three basic principles that define this unique therapeutic approach and highlight how anti-PD therapy is distinct from other immunotherapeutic approaches, namely tumor site immune modulation, targeting tumor-induced immune defects, and repairing ongoing (rather than generating de novo) tumor immunity. We believe that these fundamental principles set the standard for future immunotherapies and will guide our efforts to develop more efficacious and less toxic immune therapeutics to treat human cancers. PMID:26325035

  18. Some Advanced Kidney Cancer Patients May Postpone Treatment

    MedlinePlus

    ... advanced kidney cancer that has spread require immediate, aggressive treatment, a small new study suggests. "A subset ... them the inconvenience and debilitating side effects of aggressive treatments for about a year, and in some ...

  19. Phenotype in a patient with p.D50N mutation in GJB2 gene resemble both KID and Clouston syndromes.

    PubMed

    Markova, T G; Brazhkina, N B; Bliznech, E A; Bakhshinyan, V V; Polyakov, A V; Tavartkiladze, G A

    2016-02-01

    Keratitis-ichthyosis-deafness (KID) syndrome (OMIM 148210) is a rare ectodermal dysplasia syndrome characterized by vascularizing keratitis, congenital profound sensorineural hearing loss, and progressive erythrokeratoderma. We have found a 148G-A transition in the GJB2 gene, resulting in an asp50-to-asn (D50N) substitution in a girl with congenital deafness. This finding allowed us to diagnose а KID syndrome. But clinical features were uncommon because of a mild skin manifestation, lack of keratitis and unusual appearance resembling Clouston syndrome. Molecular genetic tests showed that it was de novo mutation because parents have normal genotype. Several autosomal dominant mutations in the GJB2 gene (сonnexin 26) now established to underlie many of the affected cases, with the majority of patients harboring the p.D50N mutation. Skin disease-associated mutation of connexin proteins can cause functional disturbances in gap junction intercellular conductance. It is likely that multiple disease mechanisms are involved across the wide spectrum of hereditary diseases relating to connexin proteins. The clinical data may provide additional insights into the dysregulation mechanisms of mutations result in the disease. PMID:26810281

  20. Pd0-mediated rapid cross-coupling reactions, the rapid C-[11C]methylations, revolutionarily advancing the syntheses of short-lived PET molecular probes.

    PubMed

    Suzuki, Masaaki; Doi, Hisashi; Koyama, Hiroko; Zhang, Zhouen; Hosoya, Takamitsu; Onoe, Hirotaka; Watanabe, Yasuyoshi

    2014-06-01

    Positron emission tomography is a noninvasive method for monitoring drug (or diagnostic) behavior and its localization on the target molecules in the living systems, including the human body, using a short-lived positron-emitting radionuclide. New methodologies for introducing representative short-lived radionuclides, (11)C and (18)F, into the carbon frameworks of biologically active organic compounds have been established by developing rapid C-[(11)C]methylations and C-[(18)F]fluoromethylations using rapid Pd(0)-mediated cross-coupling reactions between [(11)C]methyl iodide (sp(3)-hybridized carbon) and an excess amount of organotributylstannane or organoboronic acid ester having sp(2) (phenyl, heteroaromatic, or alkenyl), sp(alkynyl), or sp(3) (benzyl and cinnamyl)-hybridized carbons; and [(18)F]fluoromethyl halide (iodide or bromide) and an organoboronic acid ester, respectively. These rapid reactions provide a firm foundation for an efficient and general synthesis of short-lived (11)C- or (18)F-labeled PET molecular probes to promote in vivo molecular imaging studies.

  1. Gene expression patterns through oral squamous cell carcinoma development: PD-L1 expression in primary tumor and circulating tumor cells.

    PubMed

    Oliveira-Costa, Joao Paulo; de Carvalho, Alex Fiorini; da Silveira, da Giorgia Gobbi; Amaya, Peter; Wu, Yongqi; Park, Kyoung-Joo Jenny; Gigliola, Mabel Pinilla; Lustberg, Maryam; Buim, Marcilei Eliza Cavicchioli; Ferreira, Elisa Napolitano; Kowalski, Luiz Paulo; Chalmers, Jeffrey J; Soares, Fernando Augusto; Carraro, Dirce Maria; Ribeiro-Silva, Alfredo

    2015-08-28

    Oral squamous cell carcinoma (OSCC) is the most common tumor of the oral cavity and has been associated with poor prognosis. Scarce prognostic markers are available for guiding treatment and/or sub-classifying patients. This study aims to identify biomarkers by searching for genes whose expression is increased or decreased during tumor progression (through T1 to T4 stages). Thirty-six samples from all tumor size stages (from T1 to T4) were analyzed using cDNA microarrays. Selected targets were analyzed by immunohistochemistry and in circulating tumor cells by immunofluorescence and Nanostring. Correlation was shown between PD-L1 and tumor size and lymph node metastasis, HOXB9 and tumor size, BLNK and perineural invasion, and between ZNF813 and perineural invasion. PD-L1 positivity was an independent prognostic factor in this cohort (p = 0.044, HH = 0.426). In CTCs from patients with locally advanced OSCC, we found a strong cytoplasmatic expression of PD-L1. PD-L1 is a ligand of PD-1 and is believed to limit T cell activity in inflammatory responses and limit autoimmune diseases. We demonstrated an important role for PD-L1 in primary tumors according to tumor size, and in disease specific survival. Therefore, we could further determine individuals with PD-L1+ CTCs, and possibly follow treatment using CTCs. PMID:26041877

  2. Gene expression patterns through oral squamous cell carcinoma development: PD-L1 expression in primary tumor and circulating tumor cells

    PubMed Central

    Oliveira-Costa, Joao Paulo; de Carvalho, Alex Fiorini; da Silveira, Giorgia Gobbi; Amaya, Peter; Wu, Yongqi; Park, Kyoung-Joo Jenny; Gigliola, Mabel Pinilla; Lustberg, Maryam; Buim, Marcilei Eliza Cavicchioli; Ferreira, Elisa Napolitano; Kowalski, Luiz Paulo; Chalmers, Jeffrey J.; Soares, Fernando Augusto; Carraro, Dirce Maria; Ribeiro-Silva, Alfredo

    2015-01-01

    Oral squamous cell carcinoma (OSCC) is the most common tumor of the oral cavity and has been associated with poor prognosis. Scarce prognostic markers are available for guiding treatment and/or sub-classifying patients. This study aims to identify biomarkers by searching for genes whose expression is increased or decreased during tumor progression (through T1 to T4 stages). Thirty-six samples from all tumor size stages (from T1 to T4) were analyzed using cDNA microarrays. Selected targets were analyzed by immunohistochemistry and in circulating tumor cells by immunofluorescence and Nanostring. Correlation was shown between PD-L1 and tumor size and lymph node metastasis, HOXB9 and tumor size, BLNK and perineural invasion, and between ZNF813 and perineural invasion. PD-L1 positivity was an independent prognostic factor in this cohort (p = 0.044, HH = 0.426). In CTCs from patients with locally advanced OSCC, we found a strong cytoplasmatic expression of PD-L1. PD-L1 is a ligand of PD-1 and is believed to limit T cell activity in inflammatory responses and limit autoimmune diseases. We demonstrated an important role for PD-L1 in primary tumors according to tumor size, and in disease specific survival. Therefore, we could further determine individuals with PD-L1+ CTCs, and possibly follow treatment using CTCs. PMID:26041877

  3. Enhanced T-cell immunity to osteosarcoma through antibody blockade of PD-1/PD-L1 interactions.

    PubMed

    Lussier, Danielle M; O'Neill, Lauren; Nieves, Lizbeth M; McAfee, Megan S; Holechek, Susan A; Collins, Andrea W; Dickman, Paul; Jacobsen, Jeffrey; Hingorani, Pooja; Blattman, Joseph N

    2015-04-01

    Osteosarcoma is the most common bone cancer in children and adolescents. Although 70% of patients with localized disease are cured with chemotherapy and surgical resection, patients with metastatic osteosarcoma are typically refractory to treatment. Numerous lines of evidence suggest that cytotoxic T lymphocytes (CTLs) limit the development of metastatic osteosarcoma. We have investigated the role of PD-1, an inhibitory TNFR family protein expressed on CTLs, in limiting the efficacy of immune-mediated control of metastatic osteosarcoma. We show that human metastatic, but not primary, osteosarcoma tumors express a ligand for PD-1 (PD-L1) and that tumor-infiltrating CTLs express PD-1, suggesting this pathway may limit CTLs control of metastatic osteosarcoma in patients. PD-L1 is also expressed on the K7M2 osteosarcoma tumor cell line that establishes metastases in mice, and PD-1 is expressed on tumor-infiltrating CTLs during disease progression. Blockade of PD-1/PD-L1 interactions dramatically improves the function of osteosarcoma-reactive CTLs in vitro and in vivo, and results in decreased tumor burden and increased survival in the K7M2 mouse model of metastatic osteosarcoma. Our results suggest that blockade of PD-1/PD-L1 interactions in patients with metastatic osteosarcoma should be pursued as a therapeutic strategy. PMID:25751499

  4. Intraperitoneal radiolabeled OC 125 in patients with advanced ovarian cancer

    SciTech Connect

    Finkler, N.J.; Muto, M.G.; Kassis, A.I.; Weadock, K.; Tumeh, S.S.; Zurawski, V.R. Jr.; Knapp, R.C. )

    1989-09-01

    Twenty patients with recurrent or persistent epithelial ovarian cancer failing conventional therapies were treated with a single intraperitoneal injection of iodine-131-labeled OC 125 monoclonal antibody. Rare acute side effects were nausea and mild diarrhea. At doses up to 120 mCi of iodine-131, median white blood cell and platelet count nadirs were 3.6k/microliters and 187k/microliters, respectively. Two patients acquired thyroid toxicities despite thyroid blockage with cold iodine. One patient had transient TSH elevation while remaining clinically euthyroid, and 1 patient developed activation of a thyroid nodule and clinical hyperthyroidism. Dose-limiting toxicity has not yet been observed. Twelve of 20 patients are alive 3 to 17 months following therapy. Tumor progression was noted in the majority of patients, although 3 patients had documented decreases in tumor burden of short duration. We conclude that, at the doses examined, iodine-131 OC 125 can be safely administered intraperitoneally.

  5. Future care planning: a first step to palliative care for all patients with advanced heart disease.

    PubMed

    Denvir, M A; Murray, S A; Boyd, K J

    2015-07-01

    Palliative care is recommended for patients with end-stage heart failure with several recent, randomised trials showing improvements in symptoms and quality of life and more studies underway. Future care planning provides a framework for discussing a range of palliative care problems with patients and their families. This approach can be introduced at any time during the patient's journey of care and ideally well in advance of end-of-life care. Future care planning is applicable to a wide range of patients with advanced heart disease and could be delivered systematically by cardiology teams at the time of an unplanned hospital admission, akin to cardiac rehabilitation for myocardial infarction. Integrating cardiology care and palliative care can benefit many patients with advanced heart disease at increased risk of death or hospitalisation. Larger, randomised trials are needed to assess the impact on patient outcomes and experiences.

  6. Crizotinib Improves Progression-Free Survival in Some Patients with Advanced Lung Cancer

    MedlinePlus

    ... Prevention Lung Cancer Screening Research Crizotinib Improves Progression-Free Survival in Some Patients with Advanced Lung Cancer ( ... starting treatment without their disease getting worse (progression-free survival), as assessed by radiologic review. Results Progression- ...

  7. Care of Patients at the End of Life: Advance Care Planning.

    PubMed

    Ackermann, Richard J

    2016-08-01

    Advance directives are legal documents that give instructions about how to provide care when patients develop life-threatening illnesses and can no longer communicate their wishes. Two types of documents are widely used-a living will and a durable power of attorney for health care. Most states also authorize physician orders for life-sustaining treatment. Physicians should encourage patients, particularly those with severe chronic or terminal conditions, to prepare advance directives. Medicare now reimburses billing codes for advance care consultations. Directions regarding cardiopulmonary resuscitation and artificial ventilation often are included in advance care plans, and use of artificial nutrition and hydration (ANH) also should be addressed, particularly for patients with advanced dementia. Evidence shows that in such patients, ANH does not prolong survival, increase comfort, or improve quality of life. Given the lack of benefit, physicians should recommend against use of ANH for patients with dementia. Finally, physicians should encourage use of hospice services by patients whose life expectancy is 6 months or less. Although Medicare and most other health care insurers cover hospice care, and despite evidence that patient and family satisfaction increase when hospice services are used, many patients do not use these services. PMID:27490070

  8. The PD-1/PD-Ls pathway and autoimmune diseases.

    PubMed

    Dai, Suya; Jia, Ru; Zhang, Xiao; Fang, Qiwen; Huang, Lijuan

    2014-07-01

    The programmed death (PD)-1/PD-1 ligands (PD-Ls) pathway, is a new member of the B7/CD28 family, and consists of the PD-1 receptor and its ligands PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273). Recently, it is reported that PD-1, PD-L1 and PD-L2 also have soluble forms aside from their membrane bound forms. The soluble forms increase the diversity and complexity of PD-1/PD-Ls pathway in both composition and function. The PD-1/PD-Ls pathway is broadly expressed and exerts a wider range of immunoregulatory roles in T-cell activation and tolerance compared with other B7/CD28 family members. Studies show that the PD-1/PD-Ls pathway regulates the induction and maintenance of peripheral tolerance and protects tissues from autoimmune attack in physiological conditions. In addition, it is also involved in various diseases mediated by T cells, such as autoimmunity, tumor immunity, chronic viral infections, and transplantation immunity. In this review, we will summarize the relevance of the soluble forms and the latest researches on the role of PD-1/PD-Ls pathway in autoimmune diseases.

  9. Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents.

    PubMed

    Yang, H; Bueso-Ramos, C; DiNardo, C; Estecio, M R; Davanlou, M; Geng, Q-R; Fang, Z; Nguyen, M; Pierce, S; Wei, Y; Parmar, S; Cortes, J; Kantarjian, H; Garcia-Manero, G

    2014-06-01

    Blockade of immune checkpoints is emerging as a new form of anticancer therapy. We studied the expression of programmed death ligand 1 (PD-L1), PD-L2, programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) mRNA in CD34+ cells from myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) patients (N=124). Aberrant upregulation (⩾2-fold) was observed in 34, 14, 15 and 8% of the patients. Increased expression of these four genes was also observed in peripheral blood mononuclear cells (PBMNCs) (N=61). The relative expression of PD-L1 from PBMNC was significantly higher in MDS (P=0.018) and CMML (P=0.0128) compared with AML. By immunohistochemical analysis, PD-L1 protein expression was observed in MDS CD34+ cells, whereas stroma/non-blast cellular compartment was positive for PD-1. In a cohort of patients treated with epigenetic therapy, PD-L1, PD-L2, PD-1 and CTLA4 expression was upregulated. Patients resistant to therapy had relative higher increments in gene expression compared with patients who achieved response. Treatment of leukemia cells with decitabine resulted in a dose-dependent upregulation of above genes. Exposure to decitabine resulted in partial demethylation of PD-1 in leukemia cell lines and human samples. This study suggests that PD-1 signaling may be involved in MDS pathogenesis and resistance mechanisms to hypomethylating agents. Blockade of this pathway can be a potential therapy in MDS and AML.

  10. Advance care planning: thinking ahead to achieve our patients' goals.

    PubMed

    Cairns, Rosemary

    2011-09-01

    The End of Life Care Strategy for England describes advance care planning (ACP) as a 'voluntary process of discussion about future care...concerns and wishes...values or personal goals for care, their understanding of their illness and prognosis...wishes for types of care or treatment and the availability of these' (Department of Health (DH), 2008). In Scotland, Living and Dying Well: Building on Progress (Scottish Government (SG), 2011) referred to adopting a 'thinking ahead' philosophy.

  11. The Efficacy Profile of Rotigotine During the Waking Hours in Patients With Advanced Parkinson's Disease: A Post Hoc Analysis

    PubMed Central

    LeWitt, Peter A.; Poewe, Werner; Elmer, Lawrence W.; Asgharnejad, Mahnaz; Boroojerdi, Babak; Grieger, Frank; Bauer, Lars

    2016-01-01

    Objectives Transdermal delivery of rotigotine maintains stable plasma concentrations for 24 hours. Three phase 3 studies of rotigotine as add-on to levodopa in advanced Parkinson's disease showed a significant reduction in “off” time from baseline to end of maintenance (EoM). However, detailed analyses over the range of a day have not yet been performed. The objective was to examine the time course of the efficacy profile of rotigotine throughout the day. Methods Post hoc analysis of diary data from 3 double-blind, placebo-controlled studies of rotigotine in patients with advanced Parkinson's disease inadequately controlled with levodopa, with average “off” time of ≥2.5 h/d (CLEOPATRA-PD [NCT00244387], 16-week maintenance; PREFER, 24-week maintenance; SP921 [NCT00522379], 12-week maintenance). Patients marked 30-minute intervals as “off,” “on without troublesome dyskinesia,” “on with troublesome dyskinesia,” or “sleep.” Diaries completed on the 3 days before EoM were analyzed. A 2-sample t test was performed for comparison of rotigotine + levodopa versus placebo + levodopa for mean percentage of time per status during four 6-hour periods: 12:00am (midnight) to 6:00am, 6:00am to 12:00pm (noon), noon to 6:00pm, and 6:00pm to midnight. Results Data were available for 967 patients (placebo + levodopa, 260; rotigotine + levodopa, 707). During the 24-hour period at EoM, an advantage in mean percentage time spent “off” and “on without troublesome dyskinesia” was observed with rotigotine + levodopa versus placebo + levodopa during the three 6-hour periods from 6:00am to midnight (P < 0.05; exploratory analysis). Conclusions These exploratory analyses of patients with motor fluctuations suggest that the efficacy of rotigotine transdermal patch, as captured by diary data, in reducing “off” time and increasing “on time without troublesome dyskinesia” may cover the full waking day. PMID:26882318

  12. The effect of locoregional therapies in patients with advanced hepatocellular carcinoma treated with sorafenib

    PubMed Central

    Sarpel, Umut; Spivack, John H.; Berger, Yaniv; Heskel, Marina; Aycart, Samantha N.; Sweeney, Robert; Edwards, Martin P.; Labow, Daniel M.; Kim, Edward

    2016-01-01

    Background & aims It is unknown whether the addition of locoregional therapies (LRTx) to sorafenib improves prognosis over sorafenib alone in patients with advanced hepatocellular carcinoma (HCC). The aim of this study was to assess the effect of LRTx in this population. Methods A retrospective analysis was performed of patients with advanced HCC as defined by extrahepatic metastasis, lymphadenopathy >2 cm, or gross vascular invasion. Sorafenib therapy was required for inclusion. Survival of patients who received LRTx after progression to advanced stage was compared to those who did not receive LRTx. Results Using an intention to treat analysis of 312 eligible patients, a propensity weighted proportional hazards model demonstrated LRTx as a predictor of survival (HR = 0.505, 95% CI: 0.407–0.628; P < 0.001). The greatest benefit was seen in patients with the largest tumor burden (HR = 0.305, 95% CI: 0.236–0.393; P < 0.01). Median survival in the sorafenib arm was 143 days (95% CI: 118–161) vs. 247 days (95% CI: 220–289) in the sorafenib plus LRTx arm (P < 0.001). Conclusions These results demonstrate a survival benefit with the addition of LRTx to sorafenib for patients with advanced HCC. These findings should prompt a prospective clinical trial to further assess the role of LRTx in patients with advanced HCC. PMID:27154804

  13. Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

    Cancer.gov

    A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

  14. G6PD deficiency, absence of alpha-thalassemia, and hemolytic rate at baseline are significant independent risk factors for abnormally high cerebral velocities in patients with sickle cell anemia.

    PubMed

    Bernaudin, Françoise; Verlhac, Suzanne; Chevret, Sylvie; Torres, Martine; Coic, Lena; Arnaud, Cécile; Kamdem, Annie; Hau, Isabelle; Grazia Neonato, Maria; Delacourt, Christophe

    2008-11-15

    Stroke is predicted by abnormally high cerebral velocities by transcranial doppler (TCD). This study aimed at defining predictive factors for abnormally high velocities (>/= 2 m/sec) based on the Créteil pediatric sickle cell anemia (SCA) cohort composed of 373 stroke-free SCA children. alpha genes and beta-globin haplotypes were determined. Biologic parameters were obtained at baseline. alpha-thalassemia was present in 155 of 325 and G6PD deficiency in 36 of 325 evaluated patients. TCD was abnormal in 62 of 373 patients. Multivariate logistic regression analysis showed that G6PD deficiency (odds ratio [OR] = 3.36, 95% confidence interval [CI] 1.10-10.33; P = .034), absence of alpha-thalassemia (OR = 6.45, 95% CI 2.21-18.87; P = .001), hemoglobin (OR per g/dL = 0.63, 95% CI 0.41-0.97; P = .038), and lactate dehydrogenase (LDH) levels (OR per IU/L = 1.001, 95% CI 1.000-1.002; P = .047) were independent risk factors for abnormally high velocities. This study confirms the protective effect of alpha-thalassemia and shows for the first time that G6PD deficiency and hemolysis independently increase the risk of cerebral vasculopathy.

  15. Heading perception in patients with advanced retinitis pigmentosa

    NASA Technical Reports Server (NTRS)

    Li, Li; Peli, Eli; Warren, William H.

    2002-01-01

    PURPOSE: We investigated whether retinis pigmentosa (RP) patients with residual visual field of < 100 degrees could perceive heading from optic flow. METHODS: Four RP patients and four age-matched normally sighted control subjects viewed displays simulating an observer walking over a ground. In experiment 1, subjects viewed either the entire display with free fixation (full-field condition) or through an aperture with a fixation point at the center (aperture condition). In experiment 2, patients viewed displays of different durations. RESULTS: RP patients' performance was comparable to that of the age-matched control subjects: heading judgment was better in the full-field condition than in the aperture condition. Increasing display duration from 0.5 s to 1 s improved patients' heading performance, but giving them more time (3 s) to gather more visual information did not consistently further improve their performance. CONCLUSIONS: RP patients use active scanning eye movements to compensate for their visual field loss in heading perception; they might be able to gather sufficient optic flow information for heading perception in about 1 s.

  16. [Targeting the PD-1/PD-L1 immune checkpoint signal - a new treatment strategy for cancer].

    PubMed

    Hamanishi, Junzo; Konishi, Ikuo

    2014-09-01

    Recent studies have revealed that tumor cells can acquire several mechanisms to evade host immunity in the tumor microenvironment, called cancer immune escape. One of the most important mechanisms in this system is an immunosuppressive co- signal, called immune checkpoint, in the programmed cell death-1(PD-1)/programmed death-ligand 1(PD-L1)pathway. PD-1 is mainly expressed on activated T cells, while PD-L1 is frequently expressed on tumor cells. Inhibition of the interaction between PD-1 and PD-L1 enhances T-cell response and mediates antitumor activity. Several clinical trials by several institutions and pharmaceutical companies in the world have shown the antitumor efficacy of PD-1/PD-L1 signal blockade in patients with some solid and hematological malignancies. Production of some drugs for use in anti-PD-1 therapies are on the verge of completion. Herein, we provide a background about the PD-1/PD-L1 signal and describe some previously performed foreign clinical trials, including a trial in our department.

  17. Attitudes towards and barriers to writing advance directives amongst cancer patients, healthy controls, and medical staff

    PubMed Central

    Sahm, S; Will, R; Hommel, G

    2005-01-01

    Objectives: After years of public discussion too little is still known about willingness to accept the idea of writing an advance directive among various groups of people in EU countries. We investigated knowledge about and willingness to accept such a directive in cancer patients, healthy controls, physicians, and nursing staff in Germany. Methods: Cancer patients, healthy controls, nursing staff, and physicians (n = 100 in each group) were surveyed by means of a structured questionnaire. Results: Only 18% and 19% of the patients and healthy controls respectively, and 10% of the medical staff had written an advance directive. However, 50–81% of those surveyed indicated that they wished to write one. This intention was associated with deteriorating health (p < 0.001). Only 29% of the healthy controls and 43% of the patients knew about the possibility of appointing a health care proxy. A majority in all groups believed that advance directives may influence the course of treatment (79–85%), yet half of those surveyed in all groups fear that patients could be pressurised into writing an advance directive, and 38–65% thought that relatives could abuse such documents. Conclusions: Only a minority of the participants had written an advance directive and knew about the possibility of authorising a health care proxy. Deteriorating health was associated with increasing willingness to make a directive. Despite a majority belief that advance directives may influence treatment at the end of life, other factors limit their employment, such as fear of abuse. PMID:16076965

  18. Lenvatinib and Capecitabine in Patients With Advanced Malignancies

    ClinicalTrials.gov

    2016-09-23

    Advanced Cancer; Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract

  19. A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib

    PubMed Central

    Ganjoo, K. N.; Villalobos, V. M.; Kamaya, A.; Fisher, G. A.; Butrynski, J. E.; Morgan, J. A.; Wagner, A. J.; D'Adamo, D.; McMillan, A.; Demetri, G. D.; George, S.

    2014-01-01

    Background Advanced GISTs are incurable, but often treatable for years with tyrosine kinase inhibitors (TKIs). The majority of GISTs harbor an oncogenic activating mutation in KIT or PDGFRA. Inhibition of this activating mutation with TKIs most often leads to durable disease control for many patients. However, almost all patients develop resistance to these TKIs, typically due to the development of secondary mutations, heralding the need for new therapeutic options. We conducted a phase II study evaluating the efficacy and toxicity of pazopanib, a broad spectrum TKI inhibiting KIT, VEGFRs (−1, −2, and −3), and PDGFR (-α and-β) in patients with advanced GIST following failure of at least imatinib and sunitinib. Methods Patients received pazopanib 800 mg orally once daily. All patients were assessed for efficacy with CT scans every 8 weeks (two cycles). Patients continued pazopanib until progression or unacceptable toxicity. The primary end point was the 24-week nonprogression [complete response+partial response+stable disease (SD)] rate (NPR) per RECIST 1.1. Secondary end points included PFS, OS, and toxicity. Results Between August 2011 and September 2012, a total of 25 patients were treated at two institutions. Median number of prior therapy was 3 (range 2–7). A total of 90 cycles of pazopanib were administered, with a median of two cycles (range 1 to 17+) per patient. Best response of SD at any time was observed in 12 (48%) patients. The NPR was 17% [95% confidence interval (CI) 4.5–37]. All but one patient discontinued protocol either due to PD (n = 19) or intolerance (n = 4). One patient with succinate dehydrogenase (SDH)-deficient GIST exhibited continuing disease control after 17 cycles. The median PFS for the entire cohort was 1.9 months (95% CI 1.6–5.2), and the median OS was 10.7 months (95% CI 3.9–NR). Conclusions Pazopanib was reasonably well tolerated with no unexpected toxicities. Pazopanib as a single agent has marginal activity in

  20. Technology advances in hospital practices: robotics in treatment of patients.

    PubMed

    Rosiek, Anna; Leksowski, Krzysztof

    2015-06-01

    Laparoscopic cholecystectomy is widely considered as the treatment of choice for acute cholecystitis. The safety of the procedure and its minimal invasiveness made it a valid treatment option for a patient not responding to antibiotic therapy. Our research shows that patients positively assess this treatment method, but the world's tendency is to turn to a more sophisticated method utilizing robot-assisted surgery as a gold standard. Providing patient with minimally invasive surgical procedures that utilize the state-of-the-art equipment like the da Vinci Robotic Surgical System underscores the commitment to high-quality patient care while enhancing patient safety. The advantages include minimal invasive scarring, less pain and bleeding, faster recovery time, and shorter hospital stay. The move toward less invasive and less morbid procedures and a need to re-create the true open surgical experience have paved the way for the development and application of robotic and computer-assisted systems in surgery in Poland as well as the rest of the world.

  1. Technology advances in hospital practices: robotics in treatment of patients.

    PubMed

    Rosiek, Anna; Leksowski, Krzysztof

    2015-06-01

    Laparoscopic cholecystectomy is widely considered as the treatment of choice for acute cholecystitis. The safety of the procedure and its minimal invasiveness made it a valid treatment option for a patient not responding to antibiotic therapy. Our research shows that patients positively assess this treatment method, but the world's tendency is to turn to a more sophisticated method utilizing robot-assisted surgery as a gold standard. Providing patient with minimally invasive surgical procedures that utilize the state-of-the-art equipment like the da Vinci Robotic Surgical System underscores the commitment to high-quality patient care while enhancing patient safety. The advantages include minimal invasive scarring, less pain and bleeding, faster recovery time, and shorter hospital stay. The move toward less invasive and less morbid procedures and a need to re-create the true open surgical experience have paved the way for the development and application of robotic and computer-assisted systems in surgery in Poland as well as the rest of the world. PMID:25782187

  2. Effectiveness of the Mindfulness Art Therapy Short Version for Japanese Patients with Advanced Cancer

    ERIC Educational Resources Information Center

    Ando, Michiyo; Kira, Haruko; Hayashida, Shigeru; Ito, Sayoko

    2016-01-01

    The aim of this study was to investigate the feasibility of the Mindfulness Art Therapy Short Version for Japanese patients with advanced cancer. Patients learned mindfulness practices and then made art to express their feelings in the first session. After receiving instruction on practicing mindfulness 2 weeks later, they participated in a second…

  3. Balamuthia mandrillaris and Acanthamoeba Amebic Encephalitis with Neurotoxoplasmosis Coinfection in a Patient with Advanced HIV Infection

    PubMed Central

    Chan, Joseph C.; Castellano-Sanchez, Amilcar; Hirzel, Alicia; Laowansiri, Panthipa; Tuda, Claudio; Visvesvara, Govinda S.; Qvarnstrom, Yvonne; Ratzan, Kenneth R.

    2012-01-01

    We describe a patient with advanced HIV infection and Balamuthia mandrillaris and Acanthamoeba amebic encephalitis with Toxoplasma gondii coinfection. A multidisciplinary effort and state-of-the-art diagnostic techniques were required for diagnosis. Our patient is the first reported case of an HIV-infected person with dual Balamuthia mandrillaris and Acanthamoeba amebic encephalitis with neurotoxoplasmosis coinfection. PMID:22170911

  4. CDK4/6 Inhibitor PD0332991 in Glioblastoma Treatment: Does It Have a Future?

    PubMed Central

    Schröder, Lisette B. W.; McDonald, Kerrie L.

    2015-01-01

    Glioblastoma is aggressive, highly infiltrating, and the most frequent malignant form of brain cancer. With a median survival time of only 14.6 months, when treated with the standard of care, it is essential to find new therapeutic options. A specific CDK4/6 inhibitor, PD0332991, obtained accelerated approval from the Food and Drug Administration for the treatment of patients with advanced estrogen receptor-positive and HER2-negative breast cancer. Common alterations in the cyclin D1-cyclin-dependent kinase 4/6-retinoblastoma 1 pathway in glioblastoma make PD0332991 also an interesting drug for the treatment of glioblastoma. Promising results in in vitro studies, where patient derived glioblastoma cell lines showed sensitivity to PD0332991, gave motive to start in vivo studies. Outcomes of these studies have been contrasting in terms of PD0332991 efficacy within the brain: more research is necessary to conclude whether CDK4/6 inhibitor can be beneficial in the treatment of glioblastoma. PMID:26649278

  5. PD-L1 expression in human cancers and its association with clinical outcomes

    PubMed Central

    Wang, Xin; Teng, Feifei; Kong, Li; Yu, Jinming

    2016-01-01

    PD-L1 is an immunoinhibitory molecule that suppresses the activation of T cells, leading to the progression of tumors. Overexpression of PD-L1 in cancers such as gastric cancer, hepatocellular carcinoma, renal cell carcinoma, esophageal cancer, pancreatic cancer, ovarian cancer, and bladder cancer is associated with poor clinical outcomes. In contrast, PD-L1 expression correlates with better clinical outcomes in breast cancer and merkel cell carcinoma. The prognostic value of PD-L1 expression in lung cancer, colorectal cancer, and melanoma is controversial. Blocking antibodies that target PD-1 and PD-L1 have achieved remarkable response rates in cancer patients who have PD-L1-overexpressing tumors. However, using PD-L1 as an exclusive predictive biomarker for cancer immunotherapy is questionable due to the low accuracy of PD-L1 immunohistochemistry staining. Factors that affect the accuracy of PD-L1 immunohistochemistry staining are as follows. First, antibodies used in different studies have different sensitivity. Second, in different studies, the cut-off value of PD-L1 staining positivity is different. Third, PD-L1 expression in tumors is not uniform, and sampling time and location may affect the results of PD-L1 staining. Therefore, better understanding of tumor microenvironment and use of other biomarkers such as gene marker and combined index are necessary to better identify patients who will benefit from PD-1/PD-L1 checkpoint blockade therapy. PMID:27574444

  6. PD-L1 expression in human cancers and its association with clinical outcomes.

    PubMed

    Wang, Xin; Teng, Feifei; Kong, Li; Yu, Jinming

    2016-01-01

    PD-L1 is an immunoinhibitory molecule that suppresses the activation of T cells, leading to the progression of tumors. Overexpression of PD-L1 in cancers such as gastric cancer, hepatocellular carcinoma, renal cell carcinoma, esophageal cancer, pancreatic cancer, ovarian cancer, and bladder cancer is associated with poor clinical outcomes. In contrast, PD-L1 expression correlates with better clinical outcomes in breast cancer and merkel cell carcinoma. The prognostic value of PD-L1 expression in lung cancer, colorectal cancer, and melanoma is controversial. Blocking antibodies that target PD-1 and PD-L1 have achieved remarkable response rates in cancer patients who have PD-L1-overexpressing tumors. However, using PD-L1 as an exclusive predictive biomarker for cancer immunotherapy is questionable due to the low accuracy of PD-L1 immunohistochemistry staining. Factors that affect the accuracy of PD-L1 immunohistochemistry staining are as follows. First, antibodies used in different studies have different sensitivity. Second, in different studies, the cut-off value of PD-L1 staining positivity is different. Third, PD-L1 expression in tumors is not uniform, and sampling time and location may affect the results of PD-L1 staining. Therefore, better understanding of tumor microenvironment and use of other biomarkers such as gene marker and combined index are necessary to better identify patients who will benefit from PD-1/PD-L1 checkpoint blockade therapy. PMID:27574444

  7. Expressed wishes and incidence of euthanasia in advanced lung cancer patients.

    PubMed

    Pardon, Koen; Deschepper, Reginald; Vander Stichele, Robert; Bernheim, Jan L; Mortier, Freddy; Schallier, Denis; Germonpré, Paul; Galdermans, Daniella; Van Kerckhoven, Willem; Deliens, Luc

    2012-10-01

    This study explores expressed wishes and requests for euthanasia (i.e. administration of lethal drugs at the explicit request of the patient), and incidence of end-of-life decisions with possible life-shortening effects (ELDs) in advanced lung cancer patients in Flanders, Belgium. We performed a prospective, longitudinal, observational study of a consecutive sample of advanced lung cancer patients and selected those who died within 18 months of diagnosis. Immediately after death, the pulmonologist/oncologist and general practitioner (GP) of the patient filled in a questionnaire. Information was available for 105 out of 115 deaths. According to the specialist or GP, one in five patients had expressed a wish for euthanasia; and three in four of these had made an explicit and repeated request. One in two of these received euthanasia. Of the patients who had expressed a wish for euthanasia but had not made an explicit and repeated request, none received euthanasia. Patients with a palliative treatment goal at inclusion were more likely to receive euthanasia. Death was preceded by an ELD in 62.9% of patients. To conclude, advanced lung cancer patients who expressed a euthanasia wish were often determined. Euthanasia was performed significantly more among patients whose treatment goal after diagnosis was exclusively palliative.

  8. Using Standardized Patients in Advanced Practice Nursing Education.

    ERIC Educational Resources Information Center

    Vessey, Judith A.; Huss, Karen

    2002-01-01

    Graduating nurse practitioners (n=26) completed simulated clinical encounters with standardized patients. Their performance did not reflect their results on other clinical evaluations and national certifying examinations, suggesting that simulated encounters lack validity and reliability. They may be useful for formative learning. (Contains 38…

  9. Factors influencing skin autofluorescence of patients with peritoneal dialysis.

    PubMed

    Mácsai, Emília; Benke, A; Cseh, A; Vásárhelyi, B

    2012-06-01

    Skin autofluorescence (SAF) measurement is a simple, noninvasive method to assess tissue advanced glycation end products (AGE). In patients with end-stage renal disease and in those on hemodialysis AGE production is increased. Less is known about those treated with peritoneal dialysis (PD). In this study we tested if SAF is influenced by clinical and treatment characteristics in PD patients.This cross-sectional study included 198 PD patients (of those, 128 were on traditional glucose-based solutions and 70 patients were partially switched to icodextrin-based PD). SAF measurements were done with a specific AGE Reader device. The impact of patients' age, gender, current diabetes, duration of PD, cumulative glucose exposure, body mass index, smoking habits and use of icodextrin on SAF values were tested with multiple regression analysis.Our analysis revealed that patients' age, current diabetes and icodextrin use significantly increase patients' SAF values (p = 0.015, 0.012, 0.005, respectively). AGE exposure of PD patients with diabetes and on icodextrin solution is increased. Further investigation is required whether this finding is due to the icodextrin itself or for a still unspecified clinical characteristic of PD population treated with icodextrin.

  10. Factors influencing skin autofluorescence of patients with peritoneal dialysis.

    PubMed

    Mácsai, Emília; Benke, A; Cseh, A; Vásárhelyi, B

    2012-06-01

    Skin autofluorescence (SAF) measurement is a simple, noninvasive method to assess tissue advanced glycation end products (AGE). In patients with end-stage renal disease and in those on hemodialysis AGE production is increased. Less is known about those treated with peritoneal dialysis (PD). In this study we tested if SAF is influenced by clinical and treatment characteristics in PD patients.This cross-sectional study included 198 PD patients (of those, 128 were on traditional glucose-based solutions and 70 patients were partially switched to icodextrin-based PD). SAF measurements were done with a specific AGE Reader device. The impact of patients' age, gender, current diabetes, duration of PD, cumulative glucose exposure, body mass index, smoking habits and use of icodextrin on SAF values were tested with multiple regression analysis.Our analysis revealed that patients' age, current diabetes and icodextrin use significantly increase patients' SAF values (p = 0.015, 0.012, 0.005, respectively). AGE exposure of PD patients with diabetes and on icodextrin solution is increased. Further investigation is required whether this finding is due to the icodextrin itself or for a still unspecified clinical characteristic of PD population treated with icodextrin. PMID:22849846

  11. Anxiety and depression in patients with advanced macular degeneration: current perspectives

    PubMed Central

    Cimarolli, Verena R; Casten, Robin J; Rovner, Barry W; Heyl, Vera; Sörensen, Silvia; Horowitz, Amy

    2016-01-01

    Age-related macular degeneration (AMD) – despite advances in prevention and medical treatment options – remains prevalent among older adults, often resulting in functional losses that negatively affect the mental health of older adults. In particular, the prevalence of both anxiety and depression in patients with AMD is high. Along with medical treatment options, low vision rehabilitation and AMD-specific behavioral and self-management programs have been developed and have demonstrated effectiveness in improving the mental health of AMD patients. This article reviews the prevalence of anxiety and depression in patients with advanced AMD, discusses potential mechanisms accounting for the development of depression and anxiety in AMD patients, presents the state-of the-art of available interventions for addressing anxiety and depression in AMD patients, and delineates recommendations for eye care professionals regarding how to screen for these two prevalent mental health problems and how to facilitate appropriate treatment for patients with AMD. PMID:26766899

  12. Somatosensory symptoms in unmedicated de novo patients with idiopathic Parkinson's disease.

    PubMed

    Schindlbeck, Katharina A; Mehl, Arne; Geffe, Sarah; Benik, Steffen; Tütüncü, Serdar; Klostermann, Fabian; Marzinzik, Frank

    2016-03-01

    Parkinson's disease (PD) is a neurodegenerative condition presenting with motor and non-motor symptoms including somatosensory disturbances. As neuropathic syndromes in advanced PD patients are supposed to be due to antiparkinsonian medication, we studied the presence of somatosensory symptoms and peripheral nerve function in drug naïve patients with PD as well as age-matched healthy controls. Somatosensory symptoms and signs were investigated in 39 de novo PD patients and 32 age-matched healthy controls using the modified Toronto Clinical Neuropathy Scale. To elucidate potential underlying mechanisms, peripheral nerve function was analyzed with sensory and motor neurography. About two thirds of de novo diagnosed levodopa naïve PD patients (66.7 %) reported somatosensory symptoms in comparison to one third of the control group (31.2 %) (p = 0.003). The presence of PD (p = 0.017) was a predictive factor for the occurrence of somatosensory symptoms among all participants. In contrast to the significantly higher frequency of somatosensory symptoms in patients with PD compared to controls, neurographically based peripheral nerve function did not differ between the groups. Our results indicate that somatosensory symptoms are a PD feature, which can be found when diagnosed first and independently of dopaminergic treatment. As the electrophysiologically determined peripheral nerve function was not different from that obtained in the control group, somatosensory symptoms are inherent in early PD and may be, at least partially, of central origin. PMID:26392189

  13. Clinical significance of PD-L1 and PD-L2 copy number gains in non-small-cell lung cancer

    PubMed Central

    Inoue, Yusuke; Yoshimura, Katsuhiro; Mori, Kazutaka; Kurabe, Nobuya; Kahyo, Tomoaki; Mori, Hiroki; Kawase, Akikazu; Tanahashi, Masayuki; Ogawa, Hiroshi; Inui, Naoki; Funai, Kazuhito; Shinmura, Kazuya; Niwa, Hiroshi; Suda, Takafumi; Sugimura, Haruhiko

    2016-01-01

    New reliable biomarkers are needed to predict the response to immune checkpoint inhibitors against programmed death-1 (PD-1) and its ligand (PD-L1), because PD-L1 expression on tumor cells has limited power for selecting patients who may benefit from such therapy. Here we investigated the significance of PD-L1 and PD-L2 gene copy number gains using fluorescence in situ hybridization as well as PD-L1 and PD-L2 expression in 654 patients with resected non-small-cell lung cancer. The prevalence of PD-L1 amplification and polysomy was 3.1% and 13.2%, respectively. The PD-L1 gene copy number status was in agreement with both the PD-L2 and Janus kinase 2 gene copy number statuses. PD-L1 and PD-L2 expression was observed in 30.7% and 13.1%, respectively. Both PD-L1 copy number gains and expression were associated with smoking-related tumors. Tumor cells with PD-L1 genomic gains exhibited significantly higher levels of PD-L1 expression than those without, but PD-L2 copy number gains were not related to PD-L2 augmentation. PD-L1 gene amplification and polysomy were independently associated with PD-L1 expression, with high immune infiltrates and EGFR expression in a multivariate logistic regression model. Comparative analysis between primary tumors and synchronous regional lymph node metastases revealed that the PD-L1 gene copy number alterations were highly consistent and reproducible compared with the PD-L1 expression. Both PD-L1 amplification and level of protein expression were predictors of poor survival using Cox univariate analyses. Therefore, we conclude that an increase in PD-L1 gene copy number can be a feasible alternative biomarker for predicting response to anti-PD-1/PD-L1 therapy. PMID:27050074

  14. Clinical significance of PD-L1 and PD-L2 copy number gains in non-small-cell lung cancer.

    PubMed

    Inoue, Yusuke; Yoshimura, Katsuhiro; Mori, Kazutaka; Kurabe, Nobuya; Kahyo, Tomoaki; Mori, Hiroki; Kawase, Akikazu; Tanahashi, Masayuki; Ogawa, Hiroshi; Inui, Naoki; Funai, Kazuhito; Shinmura, Kazuya; Niwa, Hiroshi; Suda, Takafumi; Sugimura, Haruhiko

    2016-05-31

    New reliable biomarkers are needed to predict the response to immune checkpoint inhibitors against programmed death-1 (PD-1) and its ligand (PD-L1), because PD-L1 expression on tumor cells has limited power for selecting patients who may benefit from such therapy. Here we investigated the significance of PD-L1 and PD-L2 gene copy number gains using fluorescence in situ hybridization as well as PD-L1 and PD-L2 expression in 654 patients with resected non-small-cell lung cancer. The prevalence of PD-L1 amplification and polysomy was 3.1% and 13.2%, respectively. The PD-L1 gene copy number status was in agreement with both the PD-L2 and Janus kinase 2 gene copy number statuses. PD-L1 and PD-L2 expression was observed in 30.7% and 13.1%, respectively. Both PD-L1 copy number gains and expression were associated with smoking-related tumors. Tumor cells with PD-L1 genomic gains exhibited significantly higher levels of PD-L1 expression than those without, but PD-L2 copy number gains were not related to PD-L2 augmentation. PD-L1 gene amplification and polysomy were independently associated with PD-L1 expression, with high immune infiltrates and EGFR expression in a multivariate logistic regression model. Comparative analysis between primary tumors and synchronous regional lymph node metastases revealed that the PD-L1 gene copy number alterations were highly consistent and reproducible compared with the PD-L1 expression. Both PD-L1 amplification and level of protein expression were predictors of poor survival using Cox univariate analyses. Therefore, we conclude that an increase in PD-L1 gene copy number can be a feasible alternative biomarker for predicting response to anti-PD-1/PD-L1 therapy. PMID:27050074

  15. Recent advances in MRI technology: Implications for image quality and patient safety

    PubMed Central

    Sobol, Wlad T.

    2012-01-01

    Recent advances in MRI technology are presented, with emphasis on how this new technology impacts clinical operations (better image quality, faster exam times, and improved throughput). In addition, implications for patient safety are discussed with emphasis on the risk of patient injury due to either high local specific absorption rate (SAR) or large cumulative energy doses delivered during long exam times. Patient comfort issues are examined as well. PMID:23961024

  16. Nonlinear analysis of the heartbeats in public patient ECGs using an automated PD2i algorithm for risk stratification of arrhythmic death

    PubMed Central

    Skinner, James E; Anchin, Jerry M; Weiss, Daniel N

    2008-01-01

    Heart rate variability (HRV) reflects both cardiac autonomic function and risk of arrhythmic death (AD). Reduced indices of HRV based on linear stochastic models are independent risk factors for AD in post-myocardial infarct cohorts. Indices based on nonlinear deterministic models have a significantly higher sensitivity and specificity for predicting AD in retrospective data. A need exists for nonlinear analytic software easily used by a medical technician. In the current study, an automated nonlinear algorithm, the time-dependent point correlation dimension (PD2i), was evaluated. The electrocardiogram (ECG) data were provided through an National Institutes of Health-sponsored internet archive (PhysioBank) and consisted of all 22 malignant arrhythmia ECG files (VF/VT) and 22 randomly selected arrhythmia files as the controls. The results were blindly calculated by automated software (Vicor 2.0, Vicor Technologies, Inc., Boca Raton, FL) and showed all analyzable VF/VT files had PD2i < 1.4 and all analyzable controls had PD2i > 1.4. Five VF/VT and six controls were excluded because surrogate testing showed the RR-intervals to contain noise, possibly resulting from the low digitization rate of the ECGs. The sensitivity was 100%, specificity 85%, relative risk > 100; p < 0.01, power > 90%. Thus, automated heartbeat analysis by the time-dependent nonlinear PD2i-algorithm can accurately stratify risk of AD in public data made available for competitive testing of algorithms. PMID:18728829

  17. PD-1, PD-L1 and PD-L2 expression in mouse prostate cancer.

    PubMed

    Yang, Shijie; Zhang, Qiuyang; Liu, Sen; Wang, Alun R; You, Zongbing

    2016-01-01

    Programmed cell death protein 1 (PD-1) and its ligands PD-L1 and PD-L2 play critical roles in maintaining an immunosuppressive tumor microenvironment. The purpose of the present study was to assess expression of PD-1, PD-L1, and PD-L2 in mouse prostate tumors. A total of 33 mouse prostate tumors derived from Pten-null mice were examined using immunohistochemical staining for PD-1, PD-L1, and PD-L2. The animals were either with interleukin-17 receptor c (Il-17rc) wild-type or knockout genotype, or fed with regular diet or high-fat diet to 30 weeks of age. We found that Il-17rc wild-type mouse prostate tumors had significantly higher levels of PD-1, PD-L1, and PD-L2 than Il-17rc knockout mouse prostate tumors. High-fat diet-induced obese mice had significantly higher levels of PD-1, PD-L1, and PD-L2 in their prostate tumors than lean mice fed with regular diet. Increased expression of PD-1, PD-L1, and PD-L2 was associated with increased number of invasive prostate tumors formed in the Il-17rc wild-type and obese mice compared to the Il-17rc knockout and lean mice, respectively. Our findings suggest that expression of PD-1, PD-L1, and PD-L2 may enhance development of mouse prostate cancer through creating an immunosuppressive tumor microenvironment.

  18. Advances in Patient-Reported Outcomes: The NIH PROMIS® Measures

    PubMed Central

    Broderick, Joan E.; DeWitt, Esi Morgan; Rothrock, Nan; Crane, Paul K.; Forrest, Christopher B.

    2013-01-01

    Patient-reported outcomes (PRO) are questionnaire measures of patients’ symptoms, functioning, and health-related quality of life. They are designed to provide important clinical information that generally cannot be captured with objective medical testing. In 2004, the National Institutes of Health launched a research initiative to improve the clinical research enterprise by developing state-of-the-art PROs. The NIH Patient-Reported Outcomes Measurement System (PROMIS) and Assessment Center are the products of that initiative. Adult, pediatric, and parent-proxy item banks have been developed by using contemporary psychometric methods, yielding rapid, accurate measurements. PROMIS currently provides tools for assessing physical, mental, and social health using short-form and computer-adaptive testing methods. The PROMIS tools are being adopted for use in clinical trials and translational research. They are also being introduced in clinical medicine to assess a broad range of disease outcomes. Recent legislative developments in the United States support greater efforts to include patients’ reports of health experience in order to evaluate treatment outcomes, engage in shared decision-making, and prioritize the focus of treatment. PROs have garnered increased attention by the Food and Drug Administration (FDA) for evaluating drugs and medical devices. Recent calls for comparative effectiveness research favor inclusion of PROs. PROs could also potentially improve quality of care and disease outcomes, provide patient-centered assessment for comparative effectiveness research, and enable a common metric for tracking outcomes across providers and medical systems. PMID:25848562

  19. Bone disease in uremic patients: advances in PTH suppression.

    PubMed

    Brancaccio, Diego; Cozzolino, Mario; Gorio, Alfredo; Di Giulio, Anna Maria; Gallieni, Maurizio

    2002-01-01

    Chronic renal failure is often complicated by altered calcium and phosphate omeostasis. Many patients develop secondary hyperparathyroidism during the course of the disease. Therefore, both prevention and treatment of secondary hyperparathyroidism are central issues in the treatment of uremic patients. Active vitamin D metabolites are important agents in uremic patients, who have a defective activity of the renal 1alpha-hydroxylase responsible for calcitriol synthesis. Howewer, treatment with calcitriol has some limitations, namely an increase in intestinal phosphate absorption, a possible calcium overload and therefore an increase in CaxP ion product. These limitations stimulated an active research on the development of vitamin D analogs with reduced effects on intestinal transport as well as on bone mobilization of calcium and phosphate. Three vitamin D analogs, which have been used in humans, are reviewed in this article: 22-oxacalcitriol (Maxacalcitol), 19-nor-1alpha,25(OH)2 vitamin D2 (Paricalcitol), and 1alpha(OH) Vitamin D2 (Doxercalciferol). In addition, a new pharmacologic approach to the treatment of secondary hyperparathyroidism has been developed: the use of agonists for the parathyroid calcium sensing receptor, or calcimimetics. AMG O73, a second generation agent, is now under clinical evaluation in phase 3 studies, and it will soon be available in clinical practice. Given the different mechanism of action, it will be possible to use it along with vitamin D analogs and non calcemic phosphate binders. A broader spectrum of therapeutic approaches will enable the nephrologist to individually tailor the treatment of secondary hyperparathyroidism. PMID:12515379

  20. Participation of patients in the development of advanced therapy medicinal products.

    PubMed

    Bignami, F; Kent, A J; Lipucci di Paola, M; Meade, N

    2011-07-01

    An increasing number of advanced therapy medicinal products (ATMPs) are under development and in clinical trials. Patients are central to this progress. In research, patients have funded, catalysed, coordinated and led projects. In regulation, patient groups have contributed to the creation of the political momentum for regulation of ATMPs, contributed to the debate and now participate in the regulatory process. Once licensed, patients will have a role in the pharmacovigilance, health technology assessment and reimbursement arrangements for these products. Patient groups contribute valuably as equal stakeholders at every step of the development of an ATMP.

  1. Impact of Diabetes and Hyperglycemia on Survival in Advanced Breast Cancer Patients

    PubMed Central

    Villarreal-Garza, Cynthia; Shaw-Dulin, Robin; Lara-Medina, Fernando; Bacon, Ludwing; Rivera, Daniel; Urzua, Lorena; Aguila, Christian; Ramirez-Morales, Rebeca; Santamaria, Julieta; Bargallo, Enrique; Mohar, Alejandro; Herrera, Luis A.

    2012-01-01

    Purpose. We examined the impact of diabetes and hyperglycemia on cancer-specific survival of patients with metastatic or recurrent breast cancer (BC). Methods. We performed a retrospective analysis of 265 patients with advanced BC receiving palliative chemotherapy. BC-specific mortality was compared for diabetic and nondiabetic patients as well as for patients that presented hyperglycemia during treatment. Results. No difference was observed between the diabetic and nondiabetic patients in terms of overall survival (OS). A difference in OS was observed between nondiabetic patients and diabetic patients who had hyperglycemia. The OS was greater in diabetic patients with proper metabolic control than diabetic patients with hyperglycemia. The risk of death was higher in patients with mean glucose levels >130 mg/dL during treatment. Several factors were associated with poor OS: tumor stage, hormone-receptor-negative tumors, HER2 negative disease, multiple metastatic sites, presence of visceral metastases, and mean glucose >130 mg/dL. Conclusion. Elevated glucose levels are associated with a poor outcome in diabetic and nondiabetic patients in contrast to patients with normoglycemic levels, conferring an elevated risk of death. According to these results, clinicians should monitor glucose levels during treatment for advanced breast cancer disease and take action to maintain normal glucose levels. PMID:22919369

  2. Advances in cancer immunology and cancer immunotherapy.

    PubMed

    Voena, Claudia; Chiarle, Roberto

    2016-02-01

    After decades of setbacks, cancer immunology is living its Golden Age. Recent advances in cancer immunology have provided new therapeutic approaches to treat cancer. The objective clinical response observed in patients treated with antibodies that block the immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) pathways, has led to their FDA approval for the treatment of melanoma in 2011 and in 2014, respectively. The anti-PD-1 antibody nivolumab has received the FDA-approval in March 2015 for squamous lung cancer treatment. In addition, antibodies targeting PD-1 or PD-L1 have demonstrated their efficacy and safety in additional tumors, including non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's lymphoma. Almost at the same time, the field of adoptive cell transfer has exploded. The chimeric antigen receptor (CAR) T technology has provided strong evidence of efficacy in the treatment of B cell malignancies, and different T cell based treatments are currently under investigation for different types of tumors. In this review we will discuss the latest advances in cancer immunology and immunotherapy as well as new treatments now under development in the clinic and potential strategies that have shown promising results in preclinical models. PMID:27011048

  3. Investigation of the oral infections and manifestations seen in patients with advanced cancer

    PubMed Central

    Xu, Lihua; Zhang, Hualin; Liu, Jinsong; Chen, Xiaowei

    2013-01-01

    Objective: A prospective, observational study was undertaken to investigate the epidemiology of oral infection among the patients with advanced malignancies, and to investigate the effects of therapy strategies and risk factors on the incidence of oral infection. Methods: The patients with advanced malignancies were enrolled into the study. The incidence of oral infection with different malignant tumor groups or different treatment methods and the diagnoses of oral infection were confirmed. Demographic data on age, gender, bed rest time, nutritional status, smoking habit and the presence of oral prosthesis were also recorded. Results: Oral infection was prevalent in 46% (391/850) of all cancer patients, with the highest rate in oral and maxillofacial cancer group (67%), followed by Hematological malignancy group (58.6%) and other groups (ranging from 43.3% to 35.3%). Oral candidiasis, oral herpes simplex, and oral mucositis were the popular infectious diseases in the patients. Chemotherapy and radiotherapy, especially combined radio- and chemotherapy, resulted in more oral infections compared with palliative care and surgery. Poor nutritional status and oral prosthesis were identified as independent risk factors associated with oral infection. Conclusion: Oral infection is prevalent among advanced cancer patients and associated with therapy methods and risk factors. More oral health care should be carried out for the patients with advanced malignant tumor. PMID:24353702

  4. The desire to die: making treatment decisions for suicidal patients who have an advance directive.

    PubMed

    Salter, Erica K

    2014-01-01

    This article enumerates and critically examines the potential grounds on which we might treat the case of a patient with an advance directive who attempted suicide, differently from one whose injuries were the result of an accident. Grounds for differentiation are distilled into two potential justifications. The first addresses the concern that withholding or withdrawing care from a patient with self-inflicted injuries would be aiding and abetting suicide.The second examines concerns about the patient's decisionmaking capacity. Ultimately, it is argued that while there might be legitimate reasons to hold the advance directive of a suicidal patient to a different standard of scrutiny, the fact that the patient's medical state was self-inflicted should not, in and of itself, necessarily invalidate the guidance of the directive. Finally, four practical recommendations are offered for negotiating similar cases.

  5. Beneficial effects through aggressive coronary screening for type 2 diabetes patients with advanced vascular complications.

    PubMed

    Tsujimoto, Tetsuro; Sugiyama, Takehiro; Yamamoto-Honda, Ritsuko; Kishimoto, Miyako; Noto, Hiroshi; Morooka, Miyako; Kubota, Kazuo; Kamimura, Munehiro; Hara, Hisao; Kajio, Hiroshi; Kakei, Masafumi; Noda, Mitsuhiko

    2016-08-01

    Glycemic control alone does not reduce cardiovascular events in patients with type 2 diabetes (T2D), and routine screening of all T2D patients for asymptomatic coronary artery disease (CAD) is not effective for preventing acute cardiac events. We examined the effectiveness of an aggressive screening protocol for asymptomatic CAD in T2D patients with advanced vascular complications.We designed a 3-year cohort study investigating the effectiveness of the aggressive coronary screening for T2D patients with advanced vascular complications and no known coronary events using propensity score adjusted analysis at a national center in Japan. Eligibility criteria included T2D without known coronary events and with any 1 of the following 4 complications: advanced diabetic retinopathy, advanced chronic kidney disease, peripheral artery disease, or cerebrovascular disease. In the aggressive screening group (n = 122), all patients received stress single photon emission computed tomography and those exhibiting myocardial perfusion abnormalities underwent coronary angiography. In the conventional screening group (n = 108), patients were examined for CAD at the discretion of their medical providers. Primary endpoint was composite outcome of cardiovascular death and nonfatal cardiovascular events.Asymptomatic CAD with ≥70% stenosis was detected in 39.3% of patients completing aggressive screening. The proportions achieving revascularization and receiving intensive medical therapy within 90 days after the screening were significantly higher in the aggressive screening group than in the conventional screening group [19.7% vs 0% (P < 0.001) and 48.4% vs 9.3% (P < 0.001), respectively]. The cumulative rate of primary composite outcome was significantly lower in the aggressive screening group according to a propensity score adjusted Cox proportional hazards model (hazard ratio, 0.35; 95% confidence interval, 0.12-0.96; P = 0.04).Aggressive coronary screening for T2D patients

  6. Measuring therapeutic alliance between oncologists and patients with advanced cancer: The Human Connection Scale

    PubMed Central

    Mack, Jennifer W; Block, Susan D.; Nilsson, Matthew; Wright, Alexi; Trice, Elizabeth; Friedlander, Robert; Paulk, Elizabeth; Prigerson, Holly G

    2009-01-01

    Objectives Patients consider having a human connection with a physician to be an important aspect of end-of-life (EOL) care. We sought to develop and validate a measure of therapeutic alliance between advanced cancer patients and their physicians, and to evaluate the effects of therapeutic alliance on EOL experiences and care. Methods We developed The Human Connection (THC) scale to measure the extent to which patients felt a sense of mutual understanding, caring, and trust with their physicians. The scale was administered to 217 advanced cancer patients along with measures of attributes hypothesized to be related to therapeutic alliance, including emotional acceptance of terminal illness. EOL outcomes in 90 patients who died during the study were also examined. Results The 16-item THC questionnaire was internally consistent (Cronbach’s α =.90) and valid, based on its expected positive association with emotional acceptance of the terminal illness (r=.31, P<.0001). THC scores were inversely related to symptom burden (r=−.19, P=.006), functional status (Karnofsky score, r=.22, P=.001), and mental illness (THC score 50.69 for patients with any DSM diagnosis versus 55.22 for those without, P=.03). THC scores were not significantly associated with EOL discussions (P=.68). Among patients who had died, EOL ICU care was inversely associated with therapeutic alliance (THC score 46.5 for those with ICU care versus 55.5 for those without, P=.002), such that patients with higher THC scores were less likely to spend time in the ICU during the last week of life. Conclusion The THC scale is a valid and reliable measure of therapeutic alliance between advanced cancer patients and their physicians. In addition, we found no evidence to suggest that EOL discussions harm patients’ therapeutic alliance. A strong therapeutic alliance is associated with emotional acceptance of a terminal illness and with decreased ICU care at the end of life among patients with advanced cancer

  7. Research advances in traditional Chinese medicine syndromes in cancer patients.

    PubMed

    Ji, Qing; Luo, Yun-quan; Wang, Wen-hai; Liu, Xuan; Li, Qi; Su, Shi-bing

    2016-01-01

    Traditional Chinese medicine (TCM) syndrome, also known as TCM ZHENG or TCM pattern, is an integral and essential part of TCM theory that helps to guide the design of individualized treatments. A TCM syndrome, in essence, is a characteristic profile of all clinical manifestations in one patient that can be readily identified by a TCM practitioner. In this article, the authors reviewed the presentations of TCM syndromes in seven common malignancies (liver, lung, gastric, breast, colorectal, pancreatic and esophageal cancers), the objectivity and the standardization of TCM syndrome differentiation, the evaluation of TCM syndrome modeling in cancer research, and syndrome differentiation-guided TCM treatment of cancers. A better understanding of TCM syndrome theory, as well as its potential biological basis, may contribute greatly to the clinical TCM diagnosis and the treatment of cancer.

  8. Evaluation of Salivary Leptin Levels in Healthy Subjects and Patients with Advanced Periodontitis

    PubMed Central

    Khorsand, Afshin; Bayani, Mojtaba; Torabi, Sepehr; Kharrazifard, Mohammad Javad; Mohammadnejhad, Fatemeh

    2016-01-01

    Objectives: Leptin is a hormone-like protein produced by the adipose tissue. It plays an important role in protection of host against inflammation and infection. Some studies have reported changes in leptin levels in the gingival crevicular fluid (GCF), saliva and blood serum of patients with periodontal disease compared to healthy individuals. The aim of the present study was to compare the salivary leptin levels in patients with advanced periodontitis and healthy individuals. Materials and Methods: In this case-control study, the salivary samples of healthy individuals and patients with advanced periodontitis with clinical attachment loss >5mm were obtained using a standardized method and the leptin levels were measured in the salivary samples by means of ELISA. The effects of the periodontal status and sex on the salivary leptin levels of both groups were statistically analyzed by two-way ANOVA. Results: The means ± standard deviation (SD) of salivary leptin levels in healthy subjects and patients with advanced periodontitis were 34.27±6.88 and 17.87±5.89 pg/mL, respectively. Statistical analysis showed that the effect of sex on the salivary leptin levels was not significant (P=0.91), while the effect of advanced periodontitis on the salivary leptin levels was significant compared to healthy individuals (P<0.0001). Conclusions: In patients with advanced periodontitis, the salivary leptin levels were significantly lower compared to healthy individuals. Thus, assessment of salivary leptin can be done as a non-invasive and simple method to determine the susceptibility of patients to advanced periodontitis. PMID:27536322

  9. Reaching Those Most in Need – A Call to Action for Advanced Parkinson’s Disease

    PubMed Central

    Agarwal, Shashank; Fleisher, Jori E

    2016-01-01

    Much of the clinical and research attention for Parkinson's Disease (PD) has focused on mild to moderate stages. As the disease advances, it can become difficult for patients to attend clinical visits. These patients are often lost to follow-up, and consequently, vanish from the pool of potential research subjects who could inform our management of this understudied population. We aim to increase awareness about this population and potential interventions to improve continuity of care and foster research in advanced PD. PMID:27708720

  10. A Randomized, Double-Blind, Placebo-Controlled Assessment of BMS-936558, a Fully Human Monoclonal Antibody to Programmed Death-1 (PD-1), in Patients with Chronic Hepatitis C Virus Infection

    PubMed Central

    Gardiner, David; Lalezari, Jay; Lawitz, Eric; DiMicco, Michael; Ghalib, Rheem; Reddy, K. Rajender; Chang, Kyong-Mi; Sulkowski, Mark; Marro, Steven O’; Anderson, Jeffrey; He, Bing; Kansra, Vikram; McPhee, Fiona; Wind-Rotolo, Megan; Grasela, Dennis; Selby, Mark; Korman, Alan J.; Lowy, Israel

    2013-01-01

    Expression of the programmed death 1 (PD-1) receptor and its ligands are implicated in the T cell exhaustion phenotype which contributes to the persistence of several chronic viral infections, including human hepatitis C virus (HCV). The antiviral potential of BMS-936558 (MDX-1106) – a fully human anti-PD-1 monoclonal immunoglobulin-G4 that blocks ligand binding – was explored in a proof-of-concept, placebo-controlled single-ascending-dose study in patients (N = 54) with chronic HCV infection. Interferon-alfa treatment-experienced patients (n = 42) were randomized 5∶1 to receive a single infusion of BMS-936558 (0.03, 0.1, 0.3, 1.0, 3.0 mg/kg [n = 5 each] or 10 mg/kg [n = 10]) or of placebo (n = 7). An additional 12 HCV treatment-naïve patients were randomized to receive 10 mg/kg BMS-936558 (n = 10) or placebo (n = 2). Patients were followed for 85 days post-dose. Five patients who received BMS-936558 (0.1 [n = 1] or 10 mg/kg) and one placebo patient achieved the primary study endpoint of a reduction in HCV RNA ≥0.5 log10 IU/mL on at least 2 consecutive visits; 3 (10 mg/kg) achieved a >4 log10 reduction. Two patients (10 mg/kg) achieved HCV RNA below the lower limit of quantitation (25 IU/mL), one of whom (a prior null-responder) remained RNA-undetectable 1 year post-study. Transient reductions in CD4+, CD8+ and CD19+ cells, including both naïve and memory CD4+ and CD8+ subsets, were observed at Day 2 without evidence of immune deficit. No clinically relevant changes in immunoglobulin subsets or treatment-related trends in circulating cytokines were noted. BMS-936558 exhibited dose-related exposure increases, with a half-life of 20–24 days. BMS-936558 was mostly well tolerated. One patient (10 mg/kg) experienced an asymptomatic grade 4 ALT elevation coincident with the onset of a 4-log viral load reduction. Six patients exhibited immune-related adverse events of mild-to-moderate intensity, including two cases of

  11. Current advances in targeted therapies for metastatic gastric cancer: improving patient care.

    PubMed

    Aguiar, Pedro Nazareth; Muniz, Thiago Pimentel; Miranda, Raelson Rodrigues; Tadokoro, Hakaru; Forones, Nora Manoukian; Monteiro, Ines-de-Paula; Castelo-Branco, Pedro; Janjigian, Yelena Y; Mello, Ramon Andrade de

    2016-03-01

    In this article, we review the literature on the current advances in targeted therapies for metastatic gastric cancer aimed at improving patient care. We conclude that the key to guiding targeted therapy is individual biomarkers, which are not completely elucidated. HER2 overexpression is the only predictive biomarker currently in use. Furthermore, it is necessary to understand that gastric tumors are heterogeneous; therefore, is impossible to evaluate a novel biological compound without evaluating personal biomarkers. The selection of patients who are able to receive each treatment is paramount for improving advanced gastric cancer survival and reducing unnecessary costs.

  12. Elevated Cellular PD1/PD-L1 Expression Confers Acquired Resistance to Cisplatin in Small Cell Lung Cancer Cells

    PubMed Central

    Yan, Fei; Pang, Jiuxia; Peng, Yong; Molina, Julian R.; Yang, Ping; Liu, Shujun

    2016-01-01

    Although small cell lung cancer (SCLC) is highly responsive to chemotherapies (e.g., cisplatin-etoposide doublet), virtually almost all responsive SCLC patients experience disease recurrence characterized by drug resistance. The mechanisms underlying cisplatin resistance remain elusive. Here we report that cell-intrinsic expression of PD1 and PD-L1, two immune checkpoints, is required for sustained expansion of SCLC cells under cisplatin selection. Indeed, PD1 and PD-L1 were expressed at a higher level in lung cancer cell lines, tumor tissues, and importantly, in SCLC cells resistant to cisplatin (H69R, H82R), when compared to respective controls. Genetic abrogation of PD1 and PD-L1 in H69R and H82R cells decreased their proliferation rate, and restored their sensitivity to cisplatin. Mechanistically, PD-L1 upregulation in H69R and H82R cells was attributed to the overexpression of DNA methyltransferase 1 (DNMT1) or receptor tyrosine kinase KIT, as knockdown of DNMT1 or KIT in H69R and H82R cells led to PD-L1 downregulation. Consequently, combined knockdown of PD-L1 with KIT or DNMT1 resulted in more pronounced inhibition of H69R and H82R cell growth. Thus, cell intrinsic PD1/PD-L1 signaling may be a predictor for poor efficacy of cisplatin treatment, and targeting the cellular PD1/PD-L1 axis may improve chemosensitization of aggressive SCLC. PMID:27610620

  13. Elevated Cellular PD1/PD-L1 Expression Confers Acquired Resistance to Cisplatin in Small Cell Lung Cancer Cells.

    PubMed

    Yan, Fei; Pang, Jiuxia; Peng, Yong; Molina, Julian R; Yang, Ping; Liu, Shujun

    2016-01-01

    Although small cell lung cancer (SCLC) is highly responsive to chemotherapies (e.g., cisplatin-etoposide doublet), virtually almost all responsive SCLC patients experience disease recurrence characterized by drug resistance. The mechanisms underlying cisplatin resistance remain elusive. Here we report that cell-intrinsic expression of PD1 and PD-L1, two immune checkpoints, is required for sustained expansion of SCLC cells under cisplatin selection. Indeed, PD1 and PD-L1 were expressed at a higher level in lung cancer cell lines, tumor tissues, and importantly, in SCLC cells resistant to cisplatin (H69R, H82R), when compared to respective controls. Genetic abrogation of PD1 and PD-L1 in H69R and H82R cells decreased their proliferation rate, and restored their sensitivity to cisplatin. Mechanistically, PD-L1 upregulation in H69R and H82R cells was attributed to the overexpression of DNA methyltransferase 1 (DNMT1) or receptor tyrosine kinase KIT, as knockdown of DNMT1 or KIT in H69R and H82R cells led to PD-L1 downregulation. Consequently, combined knockdown of PD-L1 with KIT or DNMT1 resulted in more pronounced inhibition of H69R and H82R cell growth. Thus, cell intrinsic PD1/PD-L1 signaling may be a predictor for poor efficacy of cisplatin treatment, and targeting the cellular PD1/PD-L1 axis may improve chemosensitization of aggressive SCLC. PMID:27610620

  14. The Meaning of Parenteral Hydration to Family Caregivers and Patients with Advanced Cancer Receiving Hospice Care

    PubMed Central

    Cohen, Marlene Z; Torres-Vigil, Isabel; Burbach, Beth E.; de Rosa, Allison; Bruera, Eduardo

    2012-01-01

    Context In the U.S., patients with advanced cancer who are dehydrated or have decreased oral intake virtually always receive parenteral hydration in acute care facilities but rarely in the hospice setting. Objectives To describe the meaning of hydration for terminally ill cancer patients in home hospice care and for their primary caregivers. Methods Phenomenological interviews were conducted at two time points with 85 patients and 84 caregivers enrolled in a randomized, double-blind, controlled trial examining the efficacy of parenteral hydration in patients with advanced cancer receiving hospice care in the southern U.S. Transcripts were analyzed hermeneutically by the interdisciplinary research team until consensus on the theme labels was reached. Results Patients and their family caregivers both saw hydration as meaning hope and comfort. Hope was the view that hydration might prolong a life of dignity and enhance quality of life by reducing symptoms such as fatigue and increasing patients’ alertness. Patients and caregivers also described hydration as improving patients’ comfort by reducing pain, enhancing the effectiveness of pain medication, and nourishing the body, mind and spirit. Conclusion These findings differ from traditional hospice beliefs that dehydration enhances patient comfort given that patients and their families in the study viewed fluids as enhancing comfort, dignity and quality of life. Discussion with patients and families about their preferences for hydration may help tailor care plans to meet specific patient needs. PMID:22459230

  15. Safety and efficacy of sorafenib in patients with Child-Pugh B advanced hepatocellular carcinoma

    PubMed Central

    DA FONSECA, LEONARDO GOMES; BARROSO-SOUSA, ROMUALDO; BENTO, AFONSO DA SILVA ALVES; BLANCO, BRUNA PACCOLA; VALENTE, GABRIEL LUIS; PFIFFER, TULIO EDUARDO FLESCH; HOFF, PAULO MARCELO; SABBAGA, JORGE

    2015-01-01

    Sorafenib demonstrated a survival benefit in the treatment of advanced hepatocellular carcinoma (HCC) in phase III trials. However, almost all the patients included in those trials exhibited well-preserved liver function (Child-Pugh A). The aim of this study was to describe our experience with sorafenib in Child-Pugh B HCC patients. A database of patients with advanced HCC treated with sorafenib was retrospectively evaluated. The median overall survival of Child-Pugh B patients (n=20) was 2.53 months [95% confidence interval (CI): 0.33–5.92 months] and of Child-Pugh A patients (n=100) 9.71 months (95% CI: 6.22–13.04). Child-Pugh B patients had a significantly poorer survival compared to Child-Pugh A patients (P=0.002). The toxicities were similar between the two groups. Metastasis, vascular invasion and α-fetoprotein level >1,030 ng/ml were not associated with survival among Child-Pugh B patients (P=0.281, 0.189 and 0.996, respectively). Although the survival outcomes were worse in Child-Pugh B patients treated with sorafenib, the toxicity profile was manageable. Therefore, there remains the question of whether to treat this subgroup of patients and more data are required to define the role of sorafenib in the context of liver dysfunction. PMID:26171182

  16. Impaired Financial Abilities in Parkinson’s Disease Patients With Mild Cognitive Impairment and Dementia

    PubMed Central

    Martin, Roy C.; Triebel, Kristen; Kennedy, Richard E.; Nicholas, Anthony P.; Watts, Ray L.; Stover, Natividad; Brandon, Mariko; Marson, Daniel C.

    2015-01-01

    Purpose Financial capacity (FC) is an instrumental activity of daily living (IADL) critical to independent functioning and sensitive to cognitive impairment in dementia. Little is known about FC in cognitively impaired patients with Parkinson’s disease (PD). The present study investigated FC in PD patients with prodromal and clinical dementia. Methods Participants were 20 older controls and 35 PD patients who met consensus criteria for either mild cognitive impairment (PD-MCI, n=18) or PD dementia (PDD, n=17). FC was assessed using a standardized performance based measure consisting of 9 domain and two global scores (Financial Capacity Instrument; FCI)(1). FCI domain and global performance scores were compared across groups. Capacity impairment ratings (no impairment, mild/moderate impairment, severe impairment) were calculated for each PD patient’s domain and global scores. Results Relative to controls, PD-MCI patients were impaired on both FCI global scores and domains of basic monetary skills, financial concepts, and investment decision-making. Relative to both controls and PD-MCI patients, PDD patients were impaired on virtually all FCI variables. With respect to impairment ratings, greater than 50% of PD-MCI patients and greater than 90% of PDD patients were classified as either mild/moderate or severely impaired on the two FCI global scores. Conclusions Impairment of financial capacity is already present in PD-MCI and is advanced in PDD. Complex cognitively-mediated IADLs such as financial capacity appear to be impaired early in the course of PD dementia. PMID:23899743

  17. Frequency of Elevated Hepatocellular Carcinoma (HCC) Biomarkers in Patients with Advanced Hepatitis C

    PubMed Central

    Sterling, Richard K.; Wright, Elizabeth C.; Morgan, Timothy R.; Seeff, Leonard B.; Hoefs, John C.; Di Bisceglie, Adrian M.; Dienstag, Jules L.; Lok, Anna S.

    2013-01-01

    Background Prospective studies of serum HCC biomarkers in patients with advanced hepatitis C are lacking. Aims To determine frequencies and performance of elevated alpha-fetoprotein (AFP), AFP-L3, and des-gamma-carboxy prothrombin (DCP) levels as HCC biomarkers in advanced hepatitis C. Methods Patients in the HALT-C Trial were tested every 3 months for 42 months. Screening ultrasound was performed every 12 months. Levels of biomarkers were compared in patients in whom HCC did or did not develop. Results 855 patients were evaluated; HCC developed in 46. Among patients without HCC, 73.2% had AFP consistently <20, 24.5% had at least one AFP between 20-199, while 2.3% had at least one AFP value ≥200 ng/mL; 73.7% had DCP consistently <90, 11.6% had at least one DCP between 90-149, and 14.7% had at least one DCP value ≥150 mAU/mL. AFP-L3 ≥10% was present at least once in 9.0% and in 17.1% of those with AFP >20 ng/mL. Among all patients with elevated biomarkers, a diagnosis of HCC was made in 0-31.6% (depending on the biomarker and cutoff) during the subsequent 24 months. AFP ≥200 ng/mL had the highest specificity (99%), but sensitivity was ≤20%. DCP ≥40 mAU/mL had the highest sensitivity (76%), but specificity was ≤58%. Independent predictors of elevated AFP were gender (female), race (Black), more advanced disease, and HCC. Elevated DCP was associated with more advanced disease and HCC. Conclusions Mild-moderate elevations in total AFP and DCP but not AFP-L3 occur frequently in patients with chronic hepatitis C and advanced fibrosis, are related to factors other than HCC, and are poor predictors of HCC. PMID:21931376

  18. 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

  19. Optimal pharmacotherapeutic strategies for elderly patients with advanced non-small cell lung cancer.

    PubMed

    Quoix, Elisabeth

    2011-11-01

    Increases in both life expectancy and cancer incidence with age result in a significant rise in lung cancer rates among elderly patients, with a median age at diagnosis of between 63 and 70 years. However, elderly patients are under-represented in clinical trials and generally receive suboptimal treatment, mainly because of fears about increased toxicity of chemotherapy. Indeed, physiological modification of renal and haematopoietic functions with age together with co-morbidity and associated polypharmacy may alter the metabolism of chemotherapy drugs, resulting in greater toxicity. Moreover, performance status (PS), the main prognostic factor in younger patients, does not correlate well with geriatric indexes such as activities of daily living, cognition and physical performance, and comprehensive geriatric assessment is important in elderly patients. Until 2010, based on the small number of clinical trials designed for elderly patients, monotherapy was the recommended treatment for those with advanced non-small cell lung cancer (NSCLC), whereas for fit younger patients, a platinum-based doublet was and continues to be the recommended first-line therapy. However, at the plenary session of the 2010 Annual Meeting of the American Society of Clinical Oncology, results were presented from a randomized controlled trial conducted by the French Intergroup of Thoracic Oncology that demonstrated that in PS 0-2 patients aged≥70 years with advanced NSCLC, monthly carboplatin with weekly paclitaxel resulted in significantly longer survival than single-agent therapy (vinorelbine or gemcitabine). It should be noted that even in a priori unfavourable prognostic subgroups (patients with a PS score of 2, those aged>80 years or those with an activities of daily living scale score of <6), doublet therapy was associated with a survival advantage over monotherapy. Thus, the new paradigm of treatment of elderly patients with advanced NSCLC and a PS score of 0-2 should now be monthly

  20. Considerations and controversies in the management of older patients with advanced cancer.

    PubMed

    Mohile, Supriya Gupta; Klepin, Heidi D; Rao, Arati V

    2012-01-01

    The incidence of cancer increases with age. Oncologists need to be adept at assessing physiologic and functional capacity in older patients in order to provide safe and efficacious cancer treatment. Assessment of underlying health status is especially important for older patients with advanced cancer, for whom the benefits of treatment may be low and the toxicity of treatment high. The comprehensive geriatric assessment (CGA) is the criterion standard for evaluation of the older patient. The combined data from the CGA can be used to stratify patients into categories to better predict risk for chemotherapy toxicity as well as overall outcomes. The CGA can also be used to identify and follow-up on possible functional consequences from treatment. A variety of screening tools might be useful in the oncology practice setting to identify patients who may benefit from further testing and intervention. In this chapter, we discuss how the principles of geriatrics can help improve the clinical care of older adults with advanced cancer. Specifically, we discuss assessing tolerance for treatment, options for chemotherapy scheduling and dosing for older patients with advanced cancer, and management of under-recognized symptoms in older patients with cancer.

  1. The role of neoadjuvant chemotherapy in patients with advanced (stage IIIC) epithelial ovarian cancer

    PubMed Central

    Škof, Erik; Merlo, Sebastjan; Pilko, Gasper

    2016-01-01

    Abstract Background Primary treatment of patients with advanced epithelial ovarian cancer consists of chemotherapy either before (neoadjuvant chemotherapy, NACT) or after primary surgery (adjuvant chemotherapy). The goal of primary treatment is no residual disease after surgery (R0 resection) what is associated with an improvement in survival of patients. There is, however, no evidence of survival benefits in patients with R0 resections after prior NACT. Methods We retrospectively reviewed the records of patients who were treated with diagnosis of epithelial ovarian cancer at Institute of Oncology Ljubljana in the years 2005–2007. The differences in the rates of R0 resections, progression free survival (PFS), overall survival (OS) and in five-year and eight-year survival rates between patients treated with NACT and patients who had primary surgery were compared. Results Overall 160 patients had stage IIIC epithelial ovarian cancer. Eighty patients had NACT and eighty patients had primary surgery. Patients in NACT group had higher rates of R0 resection (42% vs. 20%; p = 0.011) than patients after primary surgery. PFS was 14.1 months in NACT group and 17.7 months after primary surgery (p = 0.213). OS was 24.8 months in NACT group and 31.6 months after primary surgery (p = 0.012). In patients with R0 resections five-year and eight-year survival rates were 20.6% and 17.6% in NACT group compared to 62.5% and 62.5% after primary surgery (p < 0.0001), respectively. Conclusions Despite higher rates of R0 resections achieved by NACT, survival of patients treated with NACT was inferior to survival of patients who underwent primary surgery. NACT should only be offered to patients with advanced epithelial cancer who are not candidates for primary surgery. PMID:27679552

  2. The role of neoadjuvant chemotherapy in patients with advanced (stage IIIC) epithelial ovarian cancer

    PubMed Central

    Škof, Erik; Merlo, Sebastjan; Pilko, Gasper

    2016-01-01

    Abstract Background Primary treatment of patients with advanced epithelial ovarian cancer consists of chemotherapy either before (neoadjuvant chemotherapy, NACT) or after primary surgery (adjuvant chemotherapy). The goal of primary treatment is no residual disease after surgery (R0 resection) what is associated with an improvement in survival of patients. There is, however, no evidence of survival benefits in patients with R0 resections after prior NACT. Methods We retrospectively reviewed the records of patients who were treated with diagnosis of epithelial ovarian cancer at Institute of Oncology Ljubljana in the years 2005–2007. The differences in the rates of R0 resections, progression free survival (PFS), overall survival (OS) and in five-year and eight-year survival rates between patients treated with NACT and patients who had primary surgery were compared. Results Overall 160 patients had stage IIIC epithelial ovarian cancer. Eighty patients had NACT and eighty patients had primary surgery. Patients in NACT group had higher rates of R0 resection (42% vs. 20%; p = 0.011) than patients after primary surgery. PFS was 14.1 months in NACT group and 17.7 months after primary surgery (p = 0.213). OS was 24.8 months in NACT group and 31.6 months after primary surgery (p = 0.012). In patients with R0 resections five-year and eight-year survival rates were 20.6% and 17.6% in NACT group compared to 62.5% and 62.5% after primary surgery (p < 0.0001), respectively. Conclusions Despite higher rates of R0 resections achieved by NACT, survival of patients treated with NACT was inferior to survival of patients who underwent primary surgery. NACT should only be offered to patients with advanced epithelial cancer who are not candidates for primary surgery.

  3. Clinically Apparent Internal Mammary Nodal Metastasis in Patients With Advanced Breast Cancer: Incidence and Local Control

    SciTech Connect

    Zhang Yujing; Oh, Julia L.; Whitman, Gary J.

    2010-07-15

    Purpose: To investigate the incidence and local control of internal mammary lymph node metastases (IMN+) in patients with clinical N2 or N3 locally advanced breast cancer. Methods and Materials: We retrospectively reviewed the records of 809 breast cancer patients diagnosed with advanced nodal disease (clinical N2-3) who received radiation treatment at our institution from January 2000 December 2006. Patients were considered IMN+ on the basis of imaging studies. Results: We identified 112 of 809 patients who presented with IMN+ disease (13.8%) detected on ultrasound, computed tomography (CT), positron emission tomography/CT (PET/CT), and/or magnetic resonance imaging (MRI) studies. All 112 patients with IMN+ disease received anthracycline and taxane-based chemotherapy. Neoadjuvant chemotherapy (NCT) resulted in a complete response (CR) on imaging studies of IMN disease in 72.1% of patients. Excluding 16 patients with progressive disease, 96 patients received adjuvant radiation to the breast or the chest wall and the regional lymphatics including the IMN chain with a median dose of 60 Gy if the internal mammary lymph nodes normalized after chemotherapy and 66 Gy if they did not. The median follow-up of surviving patients was 41 months (8-118 months). For the 96 patients able to complete curative therapy, the actuarial 5-year IMN control rate, locoregional control, overall survival, and disease-free survival were 89%, 80%, 76%, and 56%. Conclusion: Over ten percent of patients with advanced nodal disease will have IMN metastases on imaging studies. Multimodality therapy including IMN irradiation achieves excellent rates of control in the IMN region and a DFS of more than 50% after curative treatment.

  4. PD-1 marks dysfunctional regulatory T cells in malignant gliomas

    PubMed Central

    Lowther, Daniel E.; Goods, Brittany A.; Lucca, Liliana E.; Lerner, Benjamin A.; Raddassi, Khadir; van Dijk, David; Hernandez, Amanda L.; Duan, Xiangguo; Gunel, Murat; Coric, Vlad; Krishnaswamy, Smita; Hafler, David A.

    2016-01-01

    Immunotherapies targeting the immune checkpoint receptor programmed cell death protein 1 (PD-1) have shown remarkable efficacy in treating cancer. CD4+CD25hiFoxP3+ Tregs are critical regulators of immune responses in autoimmunity and malignancies, but the functional status of human Tregs expressing PD-1 remains unclear. We examined functional and molecular features of PD-1hi Tregs in healthy subjects and patients with glioblastoma multiforme (GBM), combining functional assays, RNA sequencing, and cytometry by time of flight (CyTOF). In both patients with GBM and healthy subjects, circulating PD-1hi Tregs displayed reduced suppression of CD4+ effector T cells, production of IFN-γ, and molecular signatures of exhaustion. Transcriptional profiling of tumor-resident Tregs revealed that several genes coexpressed with PD-1 and associated with IFN-γ production and exhaustion as well as enrichment in exhaustion signatures compared with circulating PD-1hi Tregs. CyTOF analysis of circulating and tumor-infiltrating Tregs from patients with GBM treated with PD-1-blocking antibodies revealed that treatment shifts the profile of circulating Tregs toward a more exhausted phenotype reminiscent of that of tumor-infiltrating Tregs, further increasing IFN-γ production. Thus, high PD-1 expression on human Tregs identifies dysfunctional, exhausted Tregs secreting IFN-γ that exist in healthy individuals and are enriched in tumor infiltrates, possibly losing function as they attempt to modulate the antitumoral immune responses. PMID:27182555

  5. [Triple therapy in cirrhotic patients and those with advanced fibrosis: relevant aspects in clinical practice].

    PubMed

    Albillos, Agustín; Luis Calleja, José; Molina, Esther; Planas, Ramon; Romero-Gómez, Manuel; Turnes, Juan; Hernández-Guerra, Manuel

    2014-07-01

    The first-line option in the treatment of patients with advanced fibrosis and cirrhosis due to genotype 1 hepatitis C virus is currently triple therapy with boceprevir/telaprevir and pegylated interferon-ribavirin. However, certain limitations could constitute a barrier to starting treatment or achieving sustained viral response in these patients. These limitations include the patient's or physician's perception of treatment effectiveness in routine clinical practice-which can weight against the decision to start treatment-, the advanced stage of the disease with portal hypertension and comorbidity, treatment interruption due to poor adherence, and adverse effects, mainly anemia. In addition, it is now possible to identify patients who could benefit from a shorter therapeutic regimen with a similar cure rate. This review discusses these issues and their possible effect on the use of triple therapy. PMID:25907434

  6. Advanced practice nursing students in the patient-centered medical home: preparing for a new reality.

    PubMed

    Swartwout, Kathryn; Murphy, Marcia Pencak; Dreher, Melanie C; Behal, Raj; Haines, Alison; Ryan, Mary; Ryan, Norman; Saba, Mary

    2014-01-01

    Driven by reimbursement incentives for increased access, improved quality and reduced cost, the patient-centered medical home model of health care delivery is being adopted in primary care practices across the nation. The transition from traditional primary care models to patient-centered medical homes presents many challenges, including the assembly of a well-prepared, interprofessional provider team to achieve effective, well-coordinated care. In turn, advanced practice nursing education programs are challenged to prepare graduates who are qualified for practice in the new reality of health care reform. This article reviews the patient-centered medical home model and describes how one college of nursing joined 7 primary care physician practices to prepare advanced practice nursing students for the new realities of health care reform while supporting each practice in its transition to the patient-centered medical home. PMID:24720942

  7. Precision oncology for patients with advanced cancer: the challenges of malignant snowflakes

    PubMed Central

    Kurzrock, Razelle; Giles, Francis J

    2015-01-01

    Precision oncology implies customizing treatment to the unique molecular and biologic characteristics of each individual and their cancer. Its implementation is being facilitated by remarkable technological advances in genomic sequencing, as well as the increasing availability of targeted and immunotherapeutic drugs. Yet, next generation sequencing may be a disruptive technology in that its results suggest that classic paradigms for clinical research and practice are a poor fit with the complex reality encountered in metastatic malignancies. Indeed, it is evident that advanced tumors have heterogeneous molecular landscapes that mostly differ between patients. Traditional modes of clinical research/practice are drug centered, with a strategy of finding commonalities between patients so that they can be grouped together and treated similarly. However, if each patient with metastatic cancer has a unique molecular portfolio, a new patient-centered, N-of-one approach that utilizes individually tailored treatment is needed. PMID:26030337

  8. The evolving role of health educators in advancing patient safety: forging partnerships and leading change.

    PubMed

    Mercurio, Annette

    2007-04-01

    At least 1.5 million preventable injuries because of adverse drug events occur in the United States each year, according to an Institute of Medicine report. IOM and other organizations at the forefront of health care improvement emphasize that stronger partnerships between patients, their families, and health care providers are necessary to make health care safer. Health educators possess a skill set and an ethical framework that effectively equip them to advance patient and family-centered care and contribute in other significant ways to a safer health care system. Health educators in clinical settings are playing varied and significant roles in advancing patient safety. They are removing barriers to clear communication and forging partnerships between patients, their families, and staff. Health educators are leading patient safety culture change within their institutions and contributing to the shift from provider-centric to patient-centric systems. To expand their impact in improving patient safety, health educators in clinical settings are participating in public awareness campaigns. In seeking to enhance patient safety, health educators face a number of challenges. To successfully manage those, health educators must expand their knowledge, broaden connections, and engage patients and families in meaningful ways.

  9. Treatment approaches in patients with advanced non-small cell lung cancer and poor performance status.

    PubMed

    Govindan, Ramaswamy; Garfield, David H

    2004-12-01

    It is estimated that 30% to 40% of patients with advanced non-small cell lung cancer (NSCLC) have a poor performance status (PS)-defined as a score of 2 or higher on the Eastern Cooperative Oncology Group scale-because of their disease burden, comorbidities, or both. Survival is shorter in these patients than in those with a better PS, and they do not tolerate chemotherapy as well. There is now evidence that PS2 patients with advanced NSCLC can benefit from single-agent chemotherapy with drugs such as vinorelbine, gemcitabine, paclitaxel, pemetrexed, and docetaxel and that combination chemotherapy may have additional advantages. The optimal treatment for PS2 patients with NSCLC, however, has yet to be determined. The case histories in this article demonstrate that PS2 patients are a heterogeneous group and that selecting the chemotherapy for each patient must take into consideration comorbidities and disease-related symptoms, as well as the potential toxicity of treatment. Large prospective clinical trials are needed to determine whether, and in which patients, combination chemotherapy or novel agents, such as the epidermal growth factor receptor inhibitors or paclitaxel poliglumex, have advantages. Three large phase III trials-Selective Targeting for Efficacy in Lung Cancer, Lower Adverse Reactions trials (STELLAR)-are now being conducted in PS2 patients with NSCLC. It is hoped that their findings will aid in determining the best treatment options for these patients.

  10. Implication of combined PD-L1/PD-1 blockade with cytokine-induced killer cells as a synergistic immunotherapy for gastrointestinal cancer.

    PubMed

    Dai, Congqi; Lin, Fengjuan; Geng, Ruixuan; Ge, Xiaoxiao; Tang, Wenbo; Chang, Jinjia; Wu, Zheng; Liu, Xinyang; Lin, Ying; Zhang, Zhe; Li, Jin

    2016-03-01

    Cytokine-induced killer (CIK) cells represent a realistic approach in cancer immunotherapy with confirmed survival benefits in the context of metastatic solid tumors. However, therapeutic effects are limited to a fraction of patients. In this study, immune-resistance elements and ideal combination therapies were explored. Initially, phenotypic analysis was performed to document CD3, CD56, NKG2D, DNAM-1, PD-L1, PD-1, CTLA-4, TIM-3, 2B4, and LAG-3 on CIK cells. Upon engagement of CIK cells with the tumor cells, expression of PD-1 on CIK cells and PD-L1 on both cells were up-regulated. Over-expression of PD-L1 levels on tumor cells via lentiviral transduction inhibited tumoricidal activity of CIK cells, and neutralizing of PD-L1/PD-1 signaling axis could enhance their tumor-killing effect. Conversely, blockade of NKG2D, a major activating receptor of CIK cells, largely caused dysfunction of CIK cells. Functional study showed an increase of NKG2D levels along with PD-L1/PD-1 blockade in the presence of other immune effector molecule secretion. Additionally, combined therapy of CIK infusion and PD-L1/PD-1 blockade caused a delay of in vivo tumor growth and exhibited a survival advantage over untreated mice. These results provide a preclinical proof-of-concept for simultaneous PD-L1/PD-1 pathways blockade along with CIK infusion as a novel immunotherapy for unresectable cancers.

  11. Development of a Companion Diagnostic PD-L1 Immunohistochemistry Assay for Pembrolizumab Therapy in Non–Small-cell Lung Cancer

    PubMed Central

    Roach, Charlotte; Zhang, Nancy; Corigliano, Ellie; Jansson, Malinka; Toland, Grant; Ponto, Gary; Dolled-Filhart, Marisa; Emancipator, Kenneth; Stanforth, Dave

    2016-01-01

    A companion diagnostic assay was codeveloped by Dako for pembrolizumab non–small-cell lung cancer clinical trials to detect PD-L1 expression by immunohistochemistry (IHC). This automated IHC assay has been analytically verified and validated using Dako’s autostainer Link 48 and 22C3 mouse anti-PD-L1 monoclonal antibody to detect the PD-L1 expression in formalin-fixed paraffin-embedded human tumor tissue specimens. The PD-L1 22C3 IHC assay was optimized for high sensitivity and specificity. Repeatability and reproducibility studies were conducted at Dako and at 3 Clinical Laboratory Improvement Amendments certified laboratories during assay development. The studies included: intersite and intrasite, interobserver and intraobserver, interinstrument, interoperator, interday, and interlot, and intraday and intrarun. All precision studies performed at Dako and external laboratories achieved >85% point-estimate agreements for all 3 agreement types (negative, positive, and overall). A clinical cutoff (tumor proportion score ≥50%) of PD-L1 expression was determined and evaluated through a phase 1 clinical trial (KEYNOTE-001) for advanced non–small-cell lung cancer patients treated with pembrolizumab. The treatment effect of pembrolizumab in the 61 subjects who had a tumor PD-L1 of tumor proportion score ≥50% was substantial, with an overall response rate of 41% (95% confidence interval, 28.6-54.3) as compared with 20.6% (95% confidence interval, 15.5-26.5) observed in the 223 subjects irrespective of PD-L1 status. PD-L1 IHC 22C3 pharmDx is a sensitive, precise, and robust companion diagnostic assay, which will facilitate safe and effective use for pembrolizumab in cancer patients. PMID:27333219

  12. Development of a Companion Diagnostic PD-L1 Immunohistochemistry Assay for Pembrolizumab Therapy in Non-Small-cell Lung Cancer.

    PubMed

    Roach, Charlotte; Zhang, Nancy; Corigliano, Ellie; Jansson, Malinka; Toland, Grant; Ponto, Gary; Dolled-Filhart, Marisa; Emancipator, Kenneth; Stanforth, Dave; Kulangara, Karina

    2016-07-01

    A companion diagnostic assay was codeveloped by Dako for pembrolizumab non-small-cell lung cancer clinical trials to detect PD-L1 expression by immunohistochemistry (IHC). This automated IHC assay has been analytically verified and validated using Dako's autostainer Link 48 and 22C3 mouse anti-PD-L1 monoclonal antibody to detect the PD-L1 expression in formalin-fixed paraffin-embedded human tumor tissue specimens. The PD-L1 22C3 IHC assay was optimized for high sensitivity and specificity. Repeatability and reproducibility studies were conducted at Dako and at 3 Clinical Laboratory Improvement Amendments certified laboratories during assay development. The studies included: intersite and intrasite, interobserver and intraobserver, interinstrument, interoperator, interday, and interlot, and intraday and intrarun. All precision studies performed at Dako and external laboratories achieved >85% point-estimate agreements for all 3 agreement types (negative, positive, and overall). A clinical cutoff (tumor proportion score ≥50%) of PD-L1 expression was determined and evaluated through a phase 1 clinical trial (KEYNOTE-001) for advanced non-small-cell lung cancer patients treated with pembrolizumab. The treatment effect of pembrolizumab in the 61 subjects who had a tumor PD-L1 of tumor proportion score ≥50% was substantial, with an overall response rate of 41% (95% confidence interval, 28.6-54.3) as compared with 20.6% (95% confidence interval, 15.5-26.5) observed in the 223 subjects irrespective of PD-L1 status. PD-L1 IHC 22C3 pharmDx is a sensitive, precise, and robust companion diagnostic assay, which will facilitate safe and effective use for pembrolizumab in cancer patients.

  13. Advance directives and living wills: the role of patient's autonomy in the Brazilian experience.

    PubMed

    Dantas, Eduardo

    2013-12-01

    This paper aims to discuss the development of the notion that the patient has the right to refuse treatment, and how the Brazilian legal system is dealing with bioethical dilemmas, such as the possibility of exercising autonomy through advance directives. The paper discusses the lack of legislation to regulate important issues in the end of life healthcare, and what ethical guidelines exist, providing physicians with ethical and legal parameters to deal with the patient's will.

  14. Left atrial appendage closure for thromboembolism prevention in patients with atrial fibrillation: advances and perspectives

    PubMed Central

    Kong, Bin; Liu, Yu; Huang, He; Jiang, Hong

    2015-01-01

    Atrial fibrillation (AF) is a frequent cause of stroke. More than 90% of thrombi were found in the left atrial appendage (LAA) in non-valvular AF. Transcatheter LAA closure has been developed as a novel approach to reduce the risk of stroke in patients with AF over the last decade. In this article, we review the recent advances and propose the possible challenges regarding the LAA closure for thromboembolism prevention in patients with AF. PMID:25713737

  15. A prospective evaluation of an interdisciplinary nutrition–rehabilitation program for patients with advanced cancer

    PubMed Central

    Gagnon, B.; Murphy, J.; Eades, M.; Lemoignan, J.; Jelowicki, M.; Carney, S.; Amdouni, S.; Di Dio, P.; Chasen, M.; MacDonald, N.

    2013-01-01

    Background Cancer can affect many dimensions of a patient’s life, and in turn, it should be targeted using a multimodal approach. We tested the extent to which an interdisciplinary nutrition–rehabilitation program can improve the well-being of patients with advanced cancer. Methods Between January 10, 2007, and September 29, 2010, 188 patients with advanced cancer enrolled in the 10–12-week program. Body weight, physical function, symptom severity, fatigue dimensions, distress level, coping ability, and overall quality of life were assessed at the start and end of the program. Results Of the enrolled patients, 70% completed the program. Patients experienced strong improvements in the physical and activity dimensions of fatigue (effect sizes: 0.8–1.1). They also experienced moderate reductions in the severity of weakness, depression, nervousness, shortness of breath, and distress (effect sizes: 0.5–0.7), and moderate improvements in Six Minute Walk Test distance, maximal gait speed, coping ability, and quality of life (effect sizes: 0.5–0.7) Furthermore, 77% of patients either maintained or increased their body weight. Conclusions Interdisciplinary nutrition–rehabilitation can be advantageous for patients with advanced cancer and should be considered an integrated part of standard palliative care. PMID:24311946

  16. Falls in ambulatory non-demented patients with Parkinson's disease.

    PubMed

    Rascol, Olivier; Perez-Lloret, Santiago; Damier, Philippe; Delval, Arnaud; Derkinderen, Pascal; Destée, Alain; Meissner, Wassilios G; Tison, Francois; Negre-Pages, Laurence

    2015-10-01

    This study aimed at determining the prevalence of falling in PD patients, to assess generic and disease-specific clinical and pharmacological factors, relationship with health-related quality of life (HR-QoL) and changes in falls from OFF to ON in patients with motor fluctuations. Six-hundred and eighty-three PD patients of the COPARK survey were evaluated (11 had missing data and were excluded from the analysis). Patients with falls were identified as those with a UPDRS Item 13 ≥ 1 in the ON condition. All patients were assessed in a standardized manner [demographics, treatments, Unified PD Rating Scale (UPDRS), Hospital Anxiety and Depression Scale, Pittsburg questionnaire and HR-QoL scales (SF36, PDQ39)]. Falling was reported by 108/672 (16%) PD patients during the ON state and prevalence increased according to PD severity, from 5% in Hoehn and Yahr stage 1-60% in stage 4. Falling was significantly related to lower HR-QoL. Falling correlated with (1) generic factors such as female gender, age at the end of academic studies and diuretics consumption, (2) motor PD-specific factors including disease severity, frozen gait, difficulties when arising from a chair, dyskinesia and higher levodopa daily equivalent dose and (3) non-motor PD-specific factors such as orthostatic hypotension and hallucinations. Falling was more frequent in OFF than in ON in 48/74 (64%) patients with motor fluctuations and remained unchanged in 27 patients (36%). In summary, falling affected a significant proportion of PD patients, especially in advanced stages. It was associated with a variety of generic and PD-specific factors and was related to reduced HR-QoL. PMID:25845678

  17. Synthesis and characterization of Pd(0), PdS, and Pd-PdO core-shell nanoparticles by solventless thermolysis of a Pd-thiolate cluster

    SciTech Connect

    Jose, Deepa; Jagirdar, Balaji R.

    2010-09-15

    Colloids of palladium nanoparticles have been prepared by the solvated metal atom dispersion (SMAD) method. The as-prepared Pd colloid consists of particles with an average diameter of 2.8{+-}0.1 nm. Digestive ripening of the as-prepared Pd colloid, a process involving refluxing the as-prepared colloid at or near the boiling point of the solvent in the presence of a passivating agent, dodecanethiol resulted in a previously reported Pd-thiolate cluster, [Pd(SC{sub 12}H{sub 25}){sub 2}]{sub 6} but did not render the expected narrowing down of the particle size distribution. Solventless thermolysis of the Pd-thiolate complex resulted in various Pd systems such as Pd(0), PdS, and Pd-PdO core-shell nanoparticles thus demonstrating its versatility. These Pd nanostructures have been characterized using high-resolution electron microscopy and powder X-ray diffraction methods. - Graphical abstract: Solventless thermolysis of a single palladium-thiolate cluster affords various Pd systems such as Pd(0), Pd-PdO core-shell, and PdS nanoparticles demonstrating the versatility of the precursor and the methodology.

  18. G6PD: The Test

    MedlinePlus

    ... is it used? Glucose-6-phosphate dehydrogenase (G6PD) enzyme testing is used to screen for and help ... and the District of Columbia. G6PD is an enzyme found in all cells, including red blood cells ( ...

  19. Urate calculi complicating orchidectomy in a patient with advanced prostatic cancer. Case report.

    PubMed

    Roosen, J U; Rungby, J A; Hvidt, V

    1991-01-01

    A patient passed 11 urate calculi after palliative orchidectomy for advanced prostatic cancer, and there was a simultaneous rise in urinary urate excretion. We believe that this rise could be the result of increased purine metabolism from lysis of tumour cells. To our knowledge this has not previously been reported.

  20. Pembrolizumab: PD-1 inhibition as a therapeutic strategy in cancer.

    PubMed

    McDermott, J; Jimeno, A

    2015-01-01

    Programmed cell death protein 1 (PD-1) and its ligands, programmed cell death 1 ligand 1 (PD-L1) and 2 (PD-L2) play an important role in regulating immune response through various mechanisms. This inhibitory action is thought to assist in immune evasion by cancer cells as PD-1, PD-L1 and PD-L2 have been found to be abnormally expressed by tumor cells and lymphocytes in the tumor microenvironment. Preclinical studies described PD-1 blockade resulting in tumor growth suppression and even decreased metastasis. This has led to the development of pembrolizumab (MK-3475), a highly selective, humanized monoclonal IgG4-kappa isotype antibody against PD-1. Early clinical trials have shown high tumor response rates and long duration of effect in previously treated advanced melanoma resulting in accelerated FDA approval for the drug in this situation. Pembrolizumab has also had success in non-small cell lung cancer and is being tested in multiple other tumor types. This review will discuss the development, preclinical data, pharmacokinetics and clinical efficacy to date of pembrolizumab.

  1. Surgery is an essential component of multimodality therapy for patients with locally advanced esophageal adenocarcinoma

    PubMed Central

    Murphy, Caitlin C.; Correa, Arlene M.; Ajani, Jaffer A.; Komaki, Ritsuko U.; Welsh, James W.; Swisher, Stephen G.; Hofstetter, Wayne L.

    2016-01-01

    Background Experience with neoadjuvant chemoradiation (CXRT) has raised questions regarding the additional benefit of surgery after locally advanced esophageal adenocarcinoma patients achieve a clinical response to CXRT. We sought to quantify the value of surgery by comparing the overall (OS) and disease-free survival (DFS) of trimodality eligible patients treated with definitive CXRT versus CXRT followed by esophagectomy. Methods We identified 143 clinical stage III esophageal adenocarcinoma patients that were eligible for trimodality therapy. All patients successfully completed neoadjuvant CXRT and were considered appropriate candidates for resection. Patients that were medically inoperable were excluded. Cox regression models were used to identify significant predictors of survival. Results Among the 143 patients eligible for surgery after completing CXRT, 114 underwent resection and 29 did not. Poorly differentiated tumors (HR=2.041, 95% CI 1.235–3.373) and surgical resection (HR=0.504, 95% CI 0.283–0.899) were the only independent predictors of OS. Patients treated with surgery had a 50% and 54% risk reduction in overall and cancer-specific mortality, respectively. Median OS (41.2 months vs. 20.3 months, p=0.012) and DFS (21.5 months vs. 11.4 months, p=0.007) were significantly improved with the addition of surgery compared to definitive CXRT. Conclusions Surgery provides a significant survival benefit to trimodality-eligible esophageal adenocarcinoma patients with locally advanced disease. PMID:23715646

  2. Case study of a chaplain's spiritual care for a patient with advanced metastatic breast cancer.

    PubMed

    Cooper, Rhonda S

    2011-01-01

    The case study seeks to describe an oncology chaplain's pastoral relationship with a 64-year-old woman with advanced metastatic breast cancer. The patient's distress was complicated by a history of anxiety and other chronic medical conditions. Approximately 16 pastoral encounters occurred during the last year of the patient's life. The patient, chaplain, and the pastoral conversations are presented as well as a retrospective assessment of them. The chaplain's interventions were appropriate for the patient's spiritual needs, particularly in regard to her fear of death, loneliness, grief that her life was "too short" and estrangement from her inherited faith tradition, with observable benefits for the patient. The oncology chaplain has a distinctive role in the healthcare team as one who can meet the patient at the point of their spiritual need, provide appropriate interventions and, thereby, ameliorate the distress, particularly in regard to death anxiety, peace of mind, and issues of meaning.

  3. The patient perspective: Quality of life in advanced heart failure with frequent hospitalisations.

    PubMed

    Nieminen, Markku S; Dickstein, Kenneth; Fonseca, Cândida; Serrano, Jose Magaña; Parissis, John; Fedele, Francesco; Wikström, Gerhard; Agostoni, Piergiuseppe; Atar, Shaul; Baholli, Loant; Brito, Dulce; Colet, Josep Comín; Édes, István; Gómez Mesa, Juan E; Gorjup, Vojka; Garza, Eduardo Herrera; González Juanatey, José R; Karanovic, Nenad; Karavidas, Apostolos; Katsytadze, Igor; Kivikko, Matti; Matskeplishvili, Simon; Merkely, Béla; Morandi, Fabrizio; Novoa, Angel; Oliva, Fabrizio; Ostadal, Petr; Pereira-Barretto, Antonio; Pollesello, Piero; Rudiger, Alain; Schwinger, Robert H G; Wieser, Manfred; Yavelov, Igor; Zymliński, Robert

    2015-07-15

    End of life is an unfortunate but inevitable phase of the heart failure patients' journey. It is often preceded by a stage in the progression of heart failure defined as advanced heart failure, and characterised by poor quality of life and frequent hospitalisations. In clinical practice, the efficacy of treatments for advanced heart failure is often assessed by parameters such as clinical status, haemodynamics, neurohormonal status, and echo/MRI indices. From the patients' perspective, however, quality-of-life-related parameters, such as functional capacity, exercise performance, psychological status, and frequency of re-hospitalisations, are more significant. The effects of therapies and interventions on these parameters are, however, underrepresented in clinical trials targeted to assess advanced heart failure treatment efficacy, and data are overall scarce. This is possibly due to a non-universal definition of the quality-of-life-related endpoints, and to the difficult standardisation of the data collection. These uncertainties also lead to difficulties in handling trade-off decisions between quality of life and survival by patients, families and healthcare providers. A panel of 34 experts in the field of cardiology and intensive cardiac care from 21 countries around the world convened for reviewing the existing data on quality-of-life in patients with advanced heart failure, discussing and reaching a consensus on the validity and significance of quality-of-life assessment methods. Gaps in routine care and research, which should be addressed, were identified. Finally, published data on the effects of current i.v. vasoactive therapies such as inotropes, inodilators, and vasodilators on quality-of-life in advanced heart failure patients were analysed.

  4. Limitation to Advanced Life Support in patients admitted to intensive care unit with integrated palliative care

    PubMed Central

    Mazutti, Sandra Regina Gonzaga; Nascimento, Andréia de Fátima; Fumis, Renata Rego Lins

    2016-01-01

    Objective To estimate the incidence of limitations to Advanced Life Support in critically ill patients admitted to an intensive care unit with integrated palliative care. Methods This retrospective cohort study included patients in the palliative care program of the intensive care unit of Hospital Paulistano over 18 years of age from May 1, 2011, to January 31, 2014. The limitations to Advanced Life Support that were analyzed included do-not-resuscitate orders, mechanical ventilation, dialysis and vasoactive drugs. Central tendency measures were calculated for quantitative variables. The chi-squared test was used to compare the characteristics of patients with or without limits to Advanced Life Support, and the Wilcoxon test was used to compare length of stay after Advanced Life Support. Confidence intervals reflecting p ≤ 0.05 were considered for statistical significance. Results A total of 3,487 patients were admitted to the intensive care unit, of whom 342 were included in the palliative care program. It was observed that after entering the palliative care program, it took a median of 2 (1 - 4) days for death to occur in the intensive care unit and 4 (2 - 11) days for hospital death to occur. Many of the limitations to Advanced Life Support (42.7%) took place on the first day of hospitalization. Cardiopulmonary resuscitation (96.8%) and ventilatory support (73.6%) were the most adopted limitations. Conclusion The contribution of palliative care integrated into the intensive care unit was important for the practice of orthothanasia, i.e., the non-extension of the life of a critically ill patient by artificial means. PMID:27626949

  5. The unified Huntington's Disease Rating Scale for advanced patients: validation and follow-up study.

    PubMed

    Youssov, Katia; Dolbeau, Guillaume; Maison, Patrick; Boissé, Marie-Françoise; Cleret de Langavant, Laurent; Roos, Raymund A C; Bachoud-Lévi, Anne-Catherine

    2013-12-01

    The Unified Huntington's Disease Rating Scale (UHDRS) adequately measures decline in patients at early and moderate stages of Huntington's disease (HD). In patients with advanced HD, floor effects hamper the evaluation, thus calling for an adjusted scale. We designed the UHDRS-For Advanced Patients (UHDRS-FAP) to improve longitudinal assessment of patients at the advanced disease stage. Sixty-nine patients with a Total Functional Capacity score ≤ 5 were recruited in France and the Netherlands. Among them, 45 patients were followed longitudinally (mean ± standard deviation, 1.6 ± 1.2 years) with the UHDRS-FAP; 30 patients also were assessed with the UHDRS. In cross-sectional analyses, the psychometric properties and inter-rater reliability of the scale were evaluated. Longitudinal analyses were used to evaluate the sensitivity to decline of the UHDRS-FAP compared with the UHDRS. Internal consistency was higher for motor (0.84) and cognitive (0.91) scores than for somatic (0.70) and behavioral (0.49) scores. Inter-rater reliability was ≥ 0.88 for all scores. The somatic score, which was specific to the UHDRS-FAP, declined over time along with motor and cognitive performance on both scales. Although performance with the two scales was correlated, the UHDRS-FAP appeared to be more sensitive to change and was the only scale that detected decline in patients with a Total Functional Capacity score ≤ 1. Neither scale detected a significant decline in behavioral scores. The results indicate that the UHDRS-FAP is reliable and more sensitive to change than the original UHDRS for cognitive and motor domains. It offers items that are relevant for daily care. Behavioral scores tended to decline, but this may reflect the decline in patients' communicative abilities.

  6. Evaluation of overall tumor cellularity after neoadjuvant chemotherapy in patient with locally advanced hypopharyngeal cancer.

    PubMed

    Chitose, Shun-ichi; Chijiwa, Hideki; Maeda, Akiteru; Umeno, Hirohito; Nakashima, Tadashi; Kiyokawa, Kensuke; Hayabuchi, Naofumi; Fujita, Hiromasa

    2012-11-01

    The aim of this study is to clarify the prognostic value of the pathological overall tumor cellularity after neoadjuvant chemotherapy for locally advanced hypopharyngeal cancer. In consecutive series of 45 operable patients with locally advanced hypopharyngeal cancer, neoadjuvant chemotherapy by cisplatin and 5-fluorouracil was administered. Pathological image analysis was performed in 30 patients using the large cross-section specimen after total resection to evaluate the overall tumor cellularity. The chemotherapeutic responses were classified according to the pathological grading scale by dividing into four categories; more than 70% overall tumor cellularity in Grade 1, between an estimated 10 and 70% in Grade 2, less than 10% in Grade 3, and no identifiable malignant tumor cells in Grade 4. The pathological grades were taken into account for analysis of the survival. In 30 available patients, 40% had Grade 1 pathological response, 30% had Grade 2, and 30% had Grade 3. There was no Grade 4 patient. The overall 5-year survival rate for these 30 patients was 53.33%. The survival rate (61.66%) for patients with Grade 2 and 3 responses was significantly higher than that (27.78%) for patients with Grade 1 response (p = 0.009). Cox regression analysis revealed that the increasing pathological grade was an independent predictor of a better survival in patients undergoing neoadjuvant chemotherapy. We have shown that the prognosis of patients with locally advanced hypopharyngeal cancer, who had been treated by neoadjuvant chemotherapy followed by total resection, can be predicted by evaluation of pathological overall tumor cellularity from the large section specimen.

  7. Prostate cancer patients may have an increased risk of coexisting advanced colorectal neoplasms

    PubMed Central

    Ko, Sun-Hye; Baeg, Myong Ki; Bae, Woong Jin; Kim, Pumsoo; Choi, Myung-Gyu

    2016-01-01

    Background/aims Patients being treated for prostate cancer (PCa) have an increased risk of developing colorectal cancer. However, whether PCa patients are inherently at a higher risk of colorectal neoplasms (CRNs) is unknown. We aimed to investigate the risk of CRNs in PCa patients. Materials and methods Patients who had been diagnosed with PCa at a tertiary medical center and had colonoscopy within 1 year of the PCa diagnosis were investigated. Patients were propensity-matched 1:2 by age and body mass index to asymptomatic control subjects who had undergone colonoscopy for routine health screening. CRN was defined as histological confirmation of an adenoma or adenocarcinoma component. Advanced CRN was defined as any of the following: 1) histological findings of high-grade dysplasia, 2) inclusion of villous features, 3) tumor ≥1 cm in size, or 4) presence of an adenocarcinoma. Risk factors for CRN and advanced CRN were evaluated by univariate and multivariate analysis. Results A total of 191 patients diagnosed with PCa had colonoscopies within 1 year of PCa diagnosis. Of these, 23 patients with a history of previous malignancy and seven with incomplete colonoscopies were excluded, leaving 161 patients in the PCa group. Although presence of PCa was not a significant risk factor for CRN by multivariate analysis, PCa was a significant risk factor for advanced CRN (odds ratio [OR] 3.300; 95% confidence interval [CI] 1.766–6.167; P<0.001). Other significant risk factors for advanced CRN were age (OR 1.050; 95% CI 1.003–1.009; P=0.036) and body mass index (OR 1.205; 95% CI 1.067–1.361; P=0.003), whereas aspirin use (OR 0.414; 95% CI 0.173–0.990; P=0.047) was a preventive factor. Conclusion The risk of advanced CRN may be significantly increased in patients with PCa. Patients with PCa should have a colonoscopy at the time of PCa diagnosis.

  8. Prostate cancer patients may have an increased risk of coexisting advanced colorectal neoplasms

    PubMed Central

    Ko, Sun-Hye; Baeg, Myong Ki; Bae, Woong Jin; Kim, Pumsoo; Choi, Myung-Gyu

    2016-01-01

    Background/aims Patients being treated for prostate cancer (PCa) have an increased risk of developing colorectal cancer. However, whether PCa patients are inherently at a higher risk of colorectal neoplasms (CRNs) is unknown. We aimed to investigate the risk of CRNs in PCa patients. Materials and methods Patients who had been diagnosed with PCa at a tertiary medical center and had colonoscopy within 1 year of the PCa diagnosis were investigated. Patients were propensity-matched 1:2 by age and body mass index to asymptomatic control subjects who had undergone colonoscopy for routine health screening. CRN was defined as histological confirmation of an adenoma or adenocarcinoma component. Advanced CRN was defined as any of the following: 1) histological findings of high-grade dysplasia, 2) inclusion of villous features, 3) tumor ≥1 cm in size, or 4) presence of an adenocarcinoma. Risk factors for CRN and advanced CRN were evaluated by univariate and multivariate analysis. Results A total of 191 patients diagnosed with PCa had colonoscopies within 1 year of PCa diagnosis. Of these, 23 patients with a history of previous malignancy and seven with incomplete colonoscopies were excluded, leaving 161 patients in the PCa group. Although presence of PCa was not a significant risk factor for CRN by multivariate analysis, PCa was a significant risk factor for advanced CRN (odds ratio [OR] 3.300; 95% confidence interval [CI] 1.766–6.167; P<0.001). Other significant risk factors for advanced CRN were age (OR 1.050; 95% CI 1.003–1.009; P=0.036) and body mass index (OR 1.205; 95% CI 1.067–1.361; P=0.003), whereas aspirin use (OR 0.414; 95% CI 0.173–0.990; P=0.047) was a preventive factor. Conclusion The risk of advanced CRN may be significantly increased in patients with PCa. Patients with PCa should have a colonoscopy at the time of PCa diagnosis. PMID:27672332

  9. [Immunomodulator Intensification of Etioropic Therapy in Patients with Advanced Pulmonary Tuberculosis].

    PubMed

    Kolomiets, V M; Abramov, A V; Rachina, N V; Rubleva, N V

    2015-01-01

    The study was aimed at possible increase of the therapy efficacy in patients with advanced tuberculosis by including immunomodulators to the treatment schemes. The data concerning 6034 patients with advanced tuberculosis, mainly fibrocavernous tuberculosis of the lungs, were analysed. Four groups of the patients were randomized. In group 1 the management of the patients included etiotropic therapy and some treatment and rehabilitation measures with the use of Cycloferon. The group 2 patients in addition to the etiotropic therapy and some treatment and rehabilitation measures were given Omega-3. In group 3 the management included the etiotropic therapy and some treatment and rehabilitation measures. In group 4 the etioropic therapy was used alone. The analysis showed that 3419 patients had primary pulmonary tuberculosis, 340 patients had relapsing tuberculosis and 2275 patients had long-term process. The etiotropic therapy efficacy was estimated after an intensive phase of not more than 3 months. In the cases with Mycobacterium tuberculosis drug resistance and some other unfavourable factors it was estimated after a 5-month intensive phase. The results confirmed that inclusion of immunomodulators to the treatment schemes allowed to increase the therapy efficacy and the patients' adherence to the treatment, as well as to shorten the period of the bacteria carriage. Thus, the use of Cycloferon in the schemes of the treatment of the patients with fibrocavernous pulmonary tuberculosis allowed to shorten the period of the pathogen carriage (as well as the drug resistant forms) in 94.1 ± 3.33% of the patients in spite of concomitant diseases. The effect of Cycloferon in such cases was likely due to both its direct immunoprotective action and the improvement of the general state of the patients and their higher adherence to the treatment.

  10. Sneddon-Wilkinson disease induced by sorafenib in a patient with advanced hepatocellular carcinoma.

    PubMed

    Tajiri, Kazuto; Nakajima, Takahiko; Kawai, Kengo; Minemura, Masami; Sugiyama, Toshiro

    2015-01-01

    Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), although it is known to cause a variety of dermatologic adverse events. Subcorneal pustular dermatosis (SCPD), also known as Sneddon-Wilkinson disease, is a rare skin eruption that accompanies various systemic disorders and may become chronically progressive. We herein describe the case of a patient who developed SCPD after sorafenib administration. The dermatologic reaction was improved by the cessation of sorafenib and worsened by its readministration. Clinicians treating HCC patients with sorafenib should be aware of the possibility of SCPD. PMID:25786448

  11. Sneddon-Wilkinson disease induced by sorafenib in a patient with advanced hepatocellular carcinoma.

    PubMed

    Tajiri, Kazuto; Nakajima, Takahiko; Kawai, Kengo; Minemura, Masami; Sugiyama, Toshiro

    2015-01-01

    Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), although it is known to cause a variety of dermatologic adverse events. Subcorneal pustular dermatosis (SCPD), also known as Sneddon-Wilkinson disease, is a rare skin eruption that accompanies various systemic disorders and may become chronically progressive. We herein describe the case of a patient who developed SCPD after sorafenib administration. The dermatologic reaction was improved by the cessation of sorafenib and worsened by its readministration. Clinicians treating HCC patients with sorafenib should be aware of the possibility of SCPD.

  12. Predictors of psychological distress in advanced cancer patients under palliative treatments.

    PubMed

    Diaz-Frutos, D; Baca-Garcia, E; García-Foncillas, J; López-Castroman, J

    2016-07-01

    This work aims to investigate the factors associated with psychological distress in advanced cancer patients under palliative treatment. We comprehensively assessed the demographic, psychosocial and health factors of 158 advanced cancer patients. Patients with high and low distress, according to the Hospital Anxiety and Depression Scale, were compared. A regression analysis was built to identify the best predictors of distress. Patients with high psychological distress (81%) were more likely to have lung cancer, suicidal ideation, hopelessness, low quality of life and poor body image than those without. In the multivariate model, only poor emotional functioning (OR = .89; 95% CI = .83-.95; p ≤ .001), hopelessness (OR = .86; 95% CI = .78-.94; p ≤ .001) and body image distortions (OR = .77; 95% CI = .68-.85; p = .005) were retained. High levels of hopelessness, impaired emotional functioning and body image distortions are the main factors associated with psychological distress in patients with advanced cancer. Potential interventions to modify these factors in palliative units are discussed. PMID:27271213

  13. Sorafenib-induced acute interstitial pneumonia in patients with advanced hepatocellular carcinoma: report of three cases.

    PubMed

    Takeda, Haruhiko; Nishikawa, Hiroki; Iguchi, Eriko; Matsuda, Fumihiro; Kita, Ryuichi; Kimura, Toru; Osaki, Yukio

    2012-01-01

    Little is known about acute interstitial pneumonia (AIP) induced by sorafenib therapy in patients with advanced hepatocellular carcinoma (HCC). Here, we present three patients with advanced HCC who developed AIP during sorafenib therapy, with fatal complications in two cases. Case 1 was a 76-year-old man who developed dyspnea. Chest CT showed interstitial pneumonia. Sorafenib was discontinued immediately, and prednisolone was started. His pneumonia resolved. A drug-induced lymphocyte stimulation test for sorafenib was positive. Case 2 was a 75-year-old man and case 3 was a 77-year-old man, both of whom developed high-grade fever and hypoxemia during sorafenib therapy, and were diagnosed with AIP. In spite of high-dose steroid therapy, their respiratory failure worsened and both patients died. In all three cases, serum KL-6 or surfactant protein D concentrations were elevated, and blood and sputum cultures did not grow pathogens. All three patients were smokers with restrictive lung disease on preoperative respiratory function testing, but did not have respiratory symptoms before sorafenib therapy. The clinical features of these three cases suggest that male gender, older age, smoking history, and lung disease are associated with acute sorafenib-induced AIP in patients with advanced HCC.

  14. The Caring Connections Project: Providing palliative care to Medicaid patients with advanced cancer.

    PubMed

    Pfeifer, Mark P; Ritchie, Christine; Scharfenberger, Jennifer; Keeney, Cynthia; Hermann, Carla; Berwick, Marilyn; Head, Barbara

    2006-01-01

    Palliative care, with its focus on symptom management, patient-centered goals, preparation for life's end, and preservation of quality of life in the face of advancing illness, is a rapidly advancing component of mainstream American medicine. Yet, access to palliative care is often lacking in the community setting and may be further hindered by the presence of healthcare disparities that impact the poor. This article presents a unique approach to assuring the availability of palliative care to Medicaid patients receiving case management services. This descriptive article describes the evolution of a palliative care management pilot program, the Caring Connections Program, beginning with the initial planning and progressing through implementation and provision of services to 56 persons. "Lessons learned" are shared to enable other providers to develop similar programs with success. Patient profiles and intervention strategies are offered to illustrate the work accomplished.

  15. Tube feeding in patients with advanced dementia: a review of the evidence.

    PubMed

    Finucane, T E; Christmas, C; Travis, K

    1999-10-13

    Patients with advanced dementia frequently develop eating difficulties and weight loss. Enteral feeding tubes are often used in this situation, yet benefits and risks of this therapy are unclear. We searched MEDLINE, 1966 through March 1999, to identify data about whether tube feeding in patients with advanced dementia can prevent aspiration pneumonia, prolong survival, reduce the risk of pressure sores or infections, improve function, or provide palliation. We found no published randomized trials that compare tube feeding with oral feeding. We found no data to suggest that tube feeding improves any of these clinically important outcomes and some data to suggest that it does not. Further, risks are substantial. The widespread practice of tube feeding should be carefully reconsidered, and we believe that for severely demented patients the practice should be discouraged on clinical grounds.

  16. Advances in non-dopaminergic treatments for Parkinson's disease

    PubMed Central

    Stayte, Sandy; Vissel, Bryce

    2014-01-01

    Since the 1960's treatments for Parkinson's disease (PD) have traditionally been directed to restore or replace dopamine, with L-Dopa being the gold standard. However, chronic L-Dopa use is associated with debilitating dyskinesias, limiting its effectiveness. This has resulted in extensive efforts to develop new therapies that work in ways other than restoring or replacing dopamine. Here we describe newly emerging non-dopaminergic therapeutic strategies for PD, including drugs targeting adenosine, glutamate, adrenergic, and serotonin receptors, as well as GLP-1 agonists, calcium channel blockers, iron chelators, anti-inflammatories, neurotrophic factors, and gene therapies. We provide a detailed account of their success in animal models and their translation to human clinical trials. We then consider how advances in understanding the mechanisms of PD, genetics, the possibility that PD may consist of multiple disease states, understanding of the etiology of PD in non-dopaminergic regions as well as advances in clinical trial design will be essential for ongoing advances. We conclude that despite the challenges ahead, patients have much cause for optimism that novel therapeutics that offer better disease management and/or which slow disease progression are inevitable. PMID:24904259

  17. Clinical and radiographic evaluation of maxillary central incisors exposure in patients undergoing maxillary advancement

    PubMed Central

    Trento, Guilherme dos Santos; Bernabé, Felipe Bueno Rosettti; da Costa, Delson João; Rebellato, Nelson Luis Barbosa; Klüppel, Leandro Eduardo; Scariot, Rafaela

    2015-01-01

    Abstract Introduction: Patients with dentofacial deformities may undergo orthodontic or orthodontic-surgical treatment. Both modalities can affect esthetics. Objective: This study aims to evaluate clinical and radiographic changes in exposure of maxillary central incisors occurring after orthognathic surgery for maxillary advancement. Methods: A total of 17 patients who underwent orthognathic surgery for maxillary advancement between September, 2010 and July, 2011 were selected. Exposure of maxillary central incisors was evaluated clinically and by lateral cephalograms. Measurements were taken one week before and three months after surgery. Data were paired in terms of sex, age, nasolabial angle, height and thickness of the upper lip, the amount of maxillary advancement, clinical exposure and inclination of maxillary central incisor by statistical tests (CI 95%). Results: After maxillary advancement, incisor clinical exposure had increased even with relaxed lips and under forced smile. Moreover, there was a mean increase of 23.33% revealed by lateral cephalograms. There was an inverse correlation between upper lip thickness and incisors postsurgical exposure revealed by radiographic images (p = 0.002). Conclusions: Significant changes in the exposure of maxillary central incisors occur after maxillary advancement, under the influence of some factors, especially lip thickness. PMID:26691970

  18. Some aspects of allogeneic stem cell transplantation in patients with myelodysplastic syndrome: advances and controversy

    PubMed Central

    Blau, Olga; Blau, Igor Wolfgang

    2014-01-01

    Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid disorders. MDS remains a disease of elderly patients; moreover, the incidence of high risk MDS is proportionally greater in elderly patients, with increased frequency of secondary acute myeloid leukemia, as well as adverse cytogenetic abnormalities. Allogeneic stem cell transplantation is a therapeutic approach with known curative potential for patients with MDS that allows the achievement of long-term disease control. Numerous controversies still exist regarding transplantation in MDS: timing of transplantation, disease status at transplantation and comorbidity, conditioning intensity, pretransplant therapy, and stem cell source. Various transplant modalities of different intensities and alternative donor sources are now in use. Current advances in transplant technology are allowing the consideration of older patients. This should result in a greater number of older patients benefiting from this potentially curative treatment modality. Despite advances in transplantation technology, there is still considerable morbidity and mortality associated with this approach. Nevertheless, with the introduction of reduced-intensity conditioning and thereby reduced early mortality, transplant numbers in MDS patients have significantly increased. Moreover, recent new developments with innovative drugs, including hypomethylating agents, have extended the therapeutic alternatives for MDS patients. Hypomethylating agents allow the delay of allogeneic stem cell transplantation by serving as an effective and well-tolerated means to reduce disease burden. PMID:25506229

  19. Unified Huntington's disease rating scale for advanced patients: validation and follow-up study.

    PubMed

    Youssov, Katia; Dolbeau, Guillaume; Maison, Patrick; Boissé, Marie-Françoise; Cleret de Langavant, Laurent; Roos, Raymund A C; Bachoud-Lévi, Anne-Catherine

    2013-10-01

    The Unified Huntington's Disease Rating Scale (UHDRS) adequately measures decline in patients at early and moderate stages of Huntington's disease (HD). In advanced patients, floor effects hamper the evaluation, thus calling for an adjusted scale. We designed the UHDRS-For Advanced Patients (UHDRS-FAP), in order to improve longitudinal assessment of patients at advanced disease stage. Sixty-nine patients with a Total Functional Capacity (TFC)  ≤  5 were recruited in France and in the Netherlands. Among them, 45 patients were followed longitudinally (mean 1.6  ±  1.2 years) with the UHDRS-FAP; 30 were also assessed with the UHDRS. Cross-sectional analyses evaluated psychometric properties and interrater reliability of the scale. Longitudinal analyses evaluated the sensitivity to decline compared to the UHDRS. Internal consistency was higher for motor and cognitive scores than for somatic and behavioral scores (0.84, 0.91, 0.70, and 0.49, respectively). Interrater reliability was  ≥  0.88 in all scores. The somatic score, specific to the UHDRS-FAP, declined over time, as well as motor and cognitive performance with both scales. Although performance with the 2 scales correlated, the UHDRS-FAP appeared more sensitive to change and was the only scale that detected decline in patients with a TFC  ≤  1. Neither scale detected a significant decline in behavioral scores. The UHDRS-FAP is reliable and more sensitive to change than the original UHDRS for cognitive and motor domains. It offers items relevant for daily care. Behavioral scores tended to decline but this may reflect the decline in the communicative abilities of the patients.

  20. The association between malnutrition and psychological distress in patients with advanced head-and-neck cancer

    PubMed Central

    Ma, L.; Poulin, P.; Feldstain, A.; Chasen, M.R.

    2013-01-01

    Objective Malnutrition and psychological distress are often seen in patients with head-and-neck cancer, but little is known about the interrelationships between those two symptoms. The present study examined the relationship between malnutrition and psychological distress in patients with advanced head-and-neck cancer. Methods Using the Patient-Generated Subjective Global Assessment, 99 patients with advanced-stage head-and-neck cancer were screened for nutrition status. The patients were also screened for psychosocial distress (using the Distress Thermometer) and for psychosocial issues (using the Problem Checklist). Any relationship between malnutrition and psychosocial distress was determined by regression and correlation analysis. We also used t-tests to compare distress levels for patients with and without specific nutrition-related symptoms. Results The study group included 80 men and 19 women [mean age: 58.4 ± 10.9 years (range: 23–85 years)]. The correlation between poorer nutrition status and level of psychological distress was significant r = 0.37 (p < 0.001). Specifically, reduced food intake and symptoms were both positively associated with distress: r = 0.27 and r = 0.29 respectively, both significant at p < 0.01. After controlling for the effects of psychosocial problems and pain, nutrition status remained a significant predictor of distress, explaining 3.8% of the variance in the distress scores of the patients (p < 0.05). Conclusions Malnutrition and symptoms were strongly related to distress in patients with advanced head-and-neck cancer. Our results suggest the need for further research into the complex relationship between nutrition status and distress and into the management of both nutrition and distress in cancer care. PMID:24311956

  1. The effects of curcumin (diferuloylmethane) on body composition of patients with advanced pancreatic cancer

    PubMed Central

    Parsons, Henrique A.; Baracos, Vickie E.; Hong, David S.; Abbruzzese, James; Bruera, Eduardo; Kurzrock, Razelle

    2016-01-01

    Background Curcumin is a natural product that is often explored by patients with cancer. Weight loss due to fat and muscle depletion is a hallmark of pancreatic cancer and is associated with worse outcomes. Studies of curcumin's effects on muscularity show conflicting results in animal models. Methods and results Retrospective matched 1:2 case-control study to evaluate the effects of curcumin on body composition (determined by computerized tomography) of 66 patients with advanced pancreatic cancer (22 treated,44 controls). Average age (SEM) was 63(1.8) years, 30/66(45%) women, median number of prior therapies was 2, median (IQR) time from advanced pancreatic cancer diagnosis to baseline image was 7(2-13.5) months (p>0.2, all variables). All patients lost weight (3.3% and 1.3%, treated vs. control, p=0.13). Treated patients lost more muscle (median [IQR] percent change −4.8[−9.1,-0.1] vs. −0.05%[−4.2, 2.6] in controls,p<0.001) and fat (median [IQR] percent change −6.8%[−15,-0.6] vs. −4.0%[−7.6, 1.3] in controls,p=0.04). Subcutaneous fat was more affected in the treated patients. Sarcopenic patients treated with curcumin(n=15) had survival of 169(115-223) days vs. 299(229-369) sarcopenic controls(p=0.024). No survival difference was found amongst non-sarcopenic patients. Conclusions Patients with advanced pancreatic cancer treated with curcumin showed significantly greater loss of subcutaneous fat and muscle than matched untreated controls. PMID:26934122

  2. Pilot Randomized Controlled Trial of Individual Meaning-Centered Psychotherapy for Patients With Advanced Cancer

    PubMed Central

    Breitbart, William; Poppito, Shannon; Rosenfeld, Barry; Vickers, Andrew J.; Li, Yuelin; Abbey, Jennifer; Olden, Megan; Pessin, Hayley; Lichtenthal, Wendy; Sjoberg, Daniel; Cassileth, Barrie R.

    2012-01-01

    Purpose Spiritual well-being and sense of meaning are important concerns for clinicians who care for patients with cancer. We developed Individual Meaning-Centered Psychotherapy (IMCP) to address the need for brief interventions targeting spiritual well-being and meaning for patients with advanced cancer. Patients and Methods Patients with stage III or IV cancer (N = 120) were randomly assigned to seven sessions of either IMCP or therapeutic massage (TM). Patients were assessed before and after completing the intervention and 2 months postintervention. Primary outcome measures assessed spiritual well-being and quality of life; secondary outcomes included anxiety, depression, hopelessness, symptom burden, and symptom-related distress. Results Of the 120 participants randomly assigned, 78 (65%) completed the post-treatment assessment and 67 (56%) completed the 2-month follow-up. At the post-treatment assessment, IMCP participants demonstrated significantly greater improvement than the control condition for the primary outcomes of spiritual well-being (b = 0.39; P <.001, including both components of spiritual well-being (sense of meaning: b = 0.34; P = .003 and faith: b = 0.42; P = .03), and quality of life (b = 0.76; P = .013). Significantly greater improvements for IMCP patients were also observed for the secondary outcomes of symptom burden (b = −6.56; P < .001) and symptom-related distress (b = −0.47; P < .001) but not for anxiety, depression, or hopelessness. At the 2-month follow-up assessment, the improvements observed for the IMCP group were no longer significantly greater than those observed for the TM group. Conclusion IMCP has clear short-term benefits for spiritual suffering and quality of life in patients with advanced cancer. Clinicians working with patients who have advanced cancer should consider IMCP as an approach to enhance quality of life and spiritual well-being. PMID:22370330

  3. Interleukin-6 and leptin as markers of energy metabolicchanges in advanced ovarian cancer patients

    PubMed Central

    Macciò, Antonio; Madeddu, Clelia; Massa, Daniela; Astara, Giorgio; Farci, Daniele; Melis, Gian Benedetto; Mantovani, Giovanni

    2009-01-01

    The progression of the neoplastic disease is characterized by specific alterations of energy metabolism and by symptoms like fatigue, anorexia, nausea, anaemia, immunodepression and poor performance status (PS). The main cause of these symptoms and metabolic abnormalities is the chronic action of proinflammatory cytokines released both by tumour and immune cells. The present study aimed to assess the relationship between markers of inflammation (C-Reactive Protein, Fibrinogen, proinflammatory cytokines) and energy metabolic status (BMI, leptin, oxidative stress) according to clinical parameters in 104 ovarian cancer patients at different stage and, moreover, to evaluate prospectively the changes of these parameters in accordance to tumour response in a subgroup of 70 advanced stage ovarian cancer patients. Advanced stage and poor PS were associated to high-grade inflammation and impaired energy metabolism. Among inflammatory mediators, interleukin (IL)-6 had a central role as predictive factor of leptin, reactive oxygen species and glutathione peroxidase. In turn, leptin considered the key marker of the nutritional status and energy metabolism, was independently determined from stage and IL-6, not only from BMI. Moreover, the evaluation of the changes of these parameters during the course of the neoplastic disease in the subgroup of advanced ovarian cancer patients clearly unveils the central role of IL-6 and leptin as early markers of the metabolic alterations and symptoms associated to disease progression in advanced stage ovarian cancer. Their assessment should be included in monitoring disease outcome, especially when cancer is no longer curable and quality of life becomes the primary endpoint. PMID:18624749

  4. Interleukin-6 and leptin as markers of energy metabolic changes in advanced ovarian cancer patients.

    PubMed

    Macciò, Antonio; Madeddu, Clelia; Massa, Daniela; Astara, Giorgio; Farci, Daniele; Melis, Gian Benedetto; Mantovani, Giovanni

    2009-09-01

    The progression of the neoplastic disease is characterized by specific alterations of energy metabolism and by symptoms like fatigue, anorexia, nausea, anaemia, immunodepression and poor performance status (PS). The main cause of these symptoms and metabolic abnormalities is the chronic action of proinflammatory cytokines released both by tumour and immune cells. The present study aimed to assess the relationship between markers of inflammation (C-Reactive Protein, Fibrinogen, proinflammatory cytokines) and energy metabolic status (BMI, leptin, oxidative stress) according to clinical parameters in 104 ovarian cancer patients at different stage and, moreover, to evaluate prospectively the changes of these parameters in accordance to tumour response in a subgroup of 70 advanced stage ovarian cancer patients. Advanced stage and poor PS were associated to high-grade inflammation and impaired energy metabolism. Among inflammatory mediators, interleukin (IL)-6 had a central role as predictive factor of leptin, reactive oxygen species and glutathione peroxidase. In turn, leptin considered the key marker of the nutritional status and energy metabolism, was independently determined from stage and IL-6, not only from BMI. Moreover, the evaluation of the changes of these parameters during the course of the neoplastic disease in the subgroup of advanced ovarian cancer patients clearly unveils the central role of IL-6 and leptin as early markers of the metabolic alterations and symptoms associated to disease progression in advanced stage ovarian cancer. Their assessment should be included in monitoring disease outcome, especially when cancer is no longer curable and quality of life becomes the primary endpoint. PMID:18624749

  5. Immunohistochemical Analysis of PD-L1 Expression in Canine Malignant Cancers and PD-1 Expression on Lymphocytes in Canine Oral Melanoma.

    PubMed

    Maekawa, Naoya; Konnai, Satoru; Okagawa, Tomohiro; Nishimori, Asami; Ikebuchi, Ryoyo; Izumi, Yusuke; Takagi, Satoshi; Kagawa, Yumiko; Nakajima, Chie; Suzuki, Yasuhiko; Kato, Yukinari; Murata, Shiro; Ohashi, Kazuhiko

    2016-01-01

    Spontaneous cancers are common diseases in dogs. Among these, some malignant cancers such as oral melanoma, osteosarcoma, hemangiosarcoma, and mast cell tumor are often recognized as clinical problems because, despite their high frequencies, current treatments for these cancers may not always achieve satisfying outcomes. The absence of effective systemic therapies against these cancers leads researchers to investigate novel therapeutic modalities, including immunotherapy. Programmed death 1 (PD-1) is a costimulatory receptor with immunosuppressive function. When it binds its ligands, PD-ligand 1 (PD-L1) or PD-L2, PD-1 on T cells negatively regulates activating signals from the T cell receptor, resulting in the inhibition of the effector function of cytotoxic T lymphocytes. Aberrant PD-L1 expression has been reported in many human cancers and is considered an immune escape mechanism for cancers. In clinical trials, anti-PD-1 or anti-PD-L1 antibodies induced tumor regression for several malignancies, including advanced melanoma, non-small cell lung carcinoma, and renal cell carcinoma. In this study, to assess the potential of the PD-1/PD-L1 axis as a novel therapeutic target for canine cancer immunotherapy, immunohistochemical analysis of PD-L1 expression in various malignant cancers of dogs was performed. Here, we show that dog oral melanoma, osteosarcoma, hemangiosarcoma, mast cell tumor, mammary adenocarcinoma, and prostate adenocarcinoma expressed PD-L1, whereas some other types of cancer did not. In addition, PD-1 was highly expressed on tumor-infiltrating lymphocytes obtained from oral melanoma, showing that lymphocytes in this cancer type might have been functionally exhausted. These results strongly encourage the clinical application of PD-1/PD-L1 inhibitors as novel therapeutic agents against these cancers in dogs. PMID:27276060

  6. Immunohistochemical Analysis of PD-L1 Expression in Canine Malignant Cancers and PD-1 Expression on Lymphocytes in Canine Oral Melanoma

    PubMed Central

    Maekawa, Naoya; Konnai, Satoru; Okagawa, Tomohiro; Nishimori, Asami; Ikebuchi, Ryoyo; Izumi, Yusuke; Takagi, Satoshi; Kagawa, Yumiko; Nakajima, Chie; Suzuki, Yasuhiko; Kato, Yukinari; Murata, Shiro; Ohashi, Kazuhiko

    2016-01-01

    Spontaneous cancers are common diseases in dogs. Among these, some malignant cancers such as oral melanoma, osteosarcoma, hemangiosarcoma, and mast cell tumor are often recognized as clinical problems because, despite their high frequencies, current treatments for these cancers may not always achieve satisfying outcomes. The absence of effective systemic therapies against these cancers leads researchers to investigate novel therapeutic modalities, including immunotherapy. Programmed death 1 (PD-1) is a costimulatory receptor with immunosuppressive function. When it binds its ligands, PD-ligand 1 (PD-L1) or PD-L2, PD-1 on T cells negatively regulates activating signals from the T cell receptor, resulting in the inhibition of the effector function of cytotoxic T lymphocytes. Aberrant PD-L1 expression has been reported in many human cancers and is considered an immune escape mechanism for cancers. In clinical trials, anti-PD-1 or anti-PD-L1 antibodies induced tumor regression for several malignancies, including advanced melanoma, non-small cell lung carcinoma, and renal cell carcinoma. In this study, to assess the potential of the PD-1/PD-L1 axis as a novel therapeutic target for canine cancer immunotherapy, immunohistochemical analysis of PD-L1 expression in various malignant cancers of dogs was performed. Here, we show that dog oral melanoma, osteosarcoma, hemangiosarcoma, mast cell tumor, mammary adenocarcinoma, and prostate adenocarcinoma expressed PD-L1, whereas some other types of cancer did not. In addition, PD-1 was highly expressed on tumor-infiltrating lymphocytes obtained from oral melanoma, showing that lymphocytes in this cancer type might have been functionally exhausted. These results strongly encourage the clinical application of PD-1/PD-L1 inhibitors as novel therapeutic agents against these cancers in dogs. PMID:27276060

  7. Advances in bypassing agent therapy for hemophilia patients with inhibitors to close care gaps and improve outcomes.

    PubMed

    Shapiro, Amy D; Hedner, Ulla

    2011-10-01

    In the past, patients with hemophilia and inhibitors have had less-than-optimal treatment and have experienced more orthopedic complications than patients without inhibitors. Bypassing agents offer the potential to close treatment gaps between inhibitor and noninhibitor patients by helping the former better attain key treatment goals, including: facilitating early initiation of treatment and hemostatic control in hemarthroses; providing effective treatment in serious hemorrhagic episodes; and performance of major surgery. Effective treatment with a bypassing agent minimizes joint and/or muscle damage and potentially can serve as an effective prophylactic agent to minimize the number of hemarthroses experienced per year, thereby mitigating the development of arthropathy. The reported efficacy of the currently available bypassing agents ranges from approximately 50-80% (50-64% in controlled studies) for plasma-derived activated prothrombin complex concentrate (pd-aPCC) and 81-91% (in controlled studies) for recombinant activated factor VII (rFVIIa), including use in major orthopedic surgery. Both bypassing agents have undergone key improvements in their formulation and/or properties in recent years. The nanofiltered, vapor-heated formulation of pd-aPCC has diminished the risk of acquiring blood-borne viral infections and the room temperature stable formulation of rFVIIa allows more convenient storage, increased ease to dissolve and inject, and smaller volumes, thereby increasing overall ease of administration. Use of recommended dosing has been demonstrated to provide effective hemostasis with a minimal number of injections for both agents. In this paper, we review the individual characteristics of pd-aPCC and rFVIIa and discuss clinical data from studies conducted in inhibitor patients that demonstrate the potential benefits of these bypassing agents in this difficult-to-treat population, and underscore the potential opportunities to close the gap in care between

  8. Foreign travel for advanced cancer patients: a guide for healthcare professionals

    PubMed Central

    Perdue, Colin; Noble, Simon

    2007-01-01

    The opportunity for a patient with advanced cancer to travel abroad may, for some, be a life affirming event during a dark period in their life. For others, what they hoped to be a time of joy may become an unmitigated disaster if they become unwell while away from the safety net of local cancer services. The rise of low budget airlines and cheaper foreign travel has led to an increase in the number of people travelling by air. Health professionals are more likely to face requests by patients to advise them on travel plans. Although foreign travel is an unrealistic goal for some patients, appropriate forward planning and proactive management can allow some patients to make an important journey abroad. This paper looks at the practical issues facing cancer patients who intend to travel overseas and offers practical advice on considerations that need to be made. PMID:17621611

  9. Foreign travel for advanced cancer patients: a guide for healthcare professionals.

    PubMed

    Perdue, Colin; Noble, Simon

    2007-07-01

    The opportunity for a patient with advanced cancer to travel abroad may, for some, be a life affirming event during a dark period in their life. For others, what they hoped to be a time of joy may become an unmitigated disaster if they become unwell while away from the safety net of local cancer services. The rise of low budget airlines and cheaper foreign travel has led to an increase in the number of people travelling by air. Health professionals are more likely to face requests by patients to advise them on travel plans. Although foreign travel is an unrealistic goal for some patients, appropriate forward planning and proactive management can allow some patients to make an important journey abroad. This paper looks at the practical issues facing cancer patients who intend to travel overseas and offers practical advice on considerations that need to be made. PMID:17621611

  10. PD-1, gender, and autoimmunity

    PubMed Central

    Dinesh, Ravi K.; Hahn, Bevra H.; Singh, Ram Pyare

    2010-01-01

    Programmed death 1 (PD-1) and its ligands (PD-L1 and PD-L2) are responsible for inhibitory T cell signaling that helps mediate the mechanisms of tolerance and immune homeostasis. The PD-1:PD-L signaling pathway has been shown to play an important role in a variety of diseases, including autoimmune conditions, chronic infection, and cancer. Recently, investigators have explored the role of sex hormones in modulating the pathway in autoimmune conditions. Exploring the effects of sex hormones on the PD-1:PD-L pathway could shed light on the gender biased nature of many autoimmune conditions as well as aide in the development of therapeutics targeting the immune system. PMID:20433954

  11. IL-2-Activated Killer Cells and Native Cytokines in Treatment of Patients with Advanced Cancer.

    PubMed

    Ostanin, Alexander A.; Chernykh, Helena R.; Leplina, Olga Y.; Shevela, Ekaterina Ya.; Niconov, Sergey D.; Kozlov, Vladimir A.

    1997-12-01

    We evaluated the efficiency/tolerability of and the immunological changes induced by the adoptive immunotherapy (AIT) with IL-2-activated killer cells, and preparation of native cytokines from swine spleen (PSS) in treatment of 20 patients with advanced cancer (10 patients with primary lung cancer; 3 with metastatic melanoma; 2 with advanced neuroblastoma; 2 with ovarian cancer; renal cancer; gastric adenocarcinoma; and colorectal cancer). The partial/minor response of duration period 2-10 months was observed in 20% of patients. 2/4 patients, who underwent partial surgical tumor resection and following AIT course, sustained the event-free survival for more than 24 months. The response to the therapy was revealed in 4/10 patients with lung cancer, 2/2 patients with neuroblastoma, of whom each had ovarian and colorectal cancers. The evaluation of a dose of infused LAKcells as well as combined i.v./local (endobronchial or endoperitoneal) LAK administration were necessary to assure positive response in patients. The cytokine and/or side effects were moderate and the combined LAK-PSS infusions were generally well tolerated by the patients. The treatment was followed by activation of the patient immune system that included: (i) rebound in amount of peripheral blood lymphocytes; (ii) gain in amount of CD3(+) T cells and those CD4(+) helper/inducer; (iii) enchantment of lymphocyte proliferation and cytokine production (IL-2, IL-1, TNF-alpha). Being injected to patients in combination with LAK cells, cytokines related to PSS action and/or those, either exogenous or secondary, and released by in vitro and in vivo, activated lymphocytes and could cause the therapeutic effects.

  12. 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.

  13. Disparities in the Use of Radiation Therapy in Patients With Local-Regionally Advanced Breast Cancer

    SciTech Connect

    Martinez, Steve R.; Beal, Shannon H.; Chen, Steven L.; Canter, Robert J.; Khatri, Vijay P.; Chen, Allen; Bold, Richard J.

    2010-11-01

    Background: Radiation therapy (RT) is indicated for the treatment of local-regionally advanced breast cancer (BCa). Hypothesis: We hypothesized that black and Hispanic patients with local-regionally advanced BCa would receive lower rates of RT than their white counterparts. Methods: The Surveillance Epidemiology and End Results database was used to identify white, black, Hispanic, and Asian patients with invasive BCa and {>=}10 metastatic lymph nodes diagnosed between 1988 and 2005. Univariate and multivariate logistic regression evaluated the relationship of race/ethnicity with use of RT. Multivariate models stratified for those undergoing mastectomy or lumpectomy. Results: Entry criteria were met by 12,653 patients. Approximately half of the patients did not receive RT. Most patients were white (72%); the remainder were Hispanic (10.4%), black (10.3%), and Asian (7.3%). On univariate analysis, Hispanics (odd ratio [OR] 0.89; 95% confidence interval [CI], 0.79-1.00) and blacks (OR 0.79; 95% CI, 0.70-0.89) were less likely to receive RT than whites. On multivariate analysis, blacks (OR 0.76; 95% CI, 0.67-0.86) and Hispanics (OR 0.80; 95% CI, 0.70-0.90) were less likely than whites to receive RT. Disparities persisted for blacks (OR 0.74; 95% CI, 0.64-0.85) and Hispanics (OR 0.77; 95% CI, 0.67-0.89) who received mastectomy, but not for those who received lumpectomy. Conclusions: Many patients with local-regionally advanced BCa do not receive RT. Blacks and Hispanics were less likely than whites to receive RT. This disparity was noted predominately in patients who received mastectomy. Future efforts at improving rates of RT are warranted. Efforts at eliminating racial/ethnic disparities should focus on black and Hispanic candidates for postmastectomy RT.

  14. Symptom clusters and quality of life among patients with advanced heart failure

    PubMed Central

    Yu, Doris SF; Chan, Helen YL; Leung, Doris YP; Hui, Elsie; Sit, Janet WH

    2016-01-01

    Objectives To identify symptom clusters among patients with advanced heart failure (HF) and the independent relationships with their quality of life (QoL). Methods This is the secondary data analysis of a cross-sectional study which interviewed 119 patients with advanced HF in the geriatric unit of a regional hospital in Hong Kong. The symptom profile and QoL were assessed by using the Edmonton Symptom Assessment Scale (ESAS) and the McGill QoL Questionnaire. Exploratory factor analysis was used to identify the symptom clusters. Hierarchical regression analysis was used to examine the independent relationships with their QoL, after adjusting the effects of age, gender, and comorbidities. Results The patients were at an advanced age (82.9 ± 6.5 years). Three distinct symptom clusters were identified: they were the distress cluster (including shortness of breath, anxiety, and depression), the decondition cluster (fatigue, drowsiness, nausea, and reduced appetite), and the discomfort cluster (pain, and sense of generalized discomfort). These three symptom clusters accounted for 63.25% of variance of the patients' symptom experience. The small to moderate correlations between these symptom clusters indicated that they were rather independent of one another. After adjusting the age, gender and comorbidities, the distress (β = −0.635, P < 0.001), the decondition (β = −0.148, P = 0.01), and the discomfort (β = −0.258, P < 0.001) symptom clusters independently predicted their QoL. Conclusions This study identified the distinctive symptom clusters among patients with advanced HF. The results shed light on the need to develop palliative care interventions for optimizing the symptom control for this life-limiting disease. PMID:27403150

  15. Selecting the best strategy of treatment in newly diagnosed advanced-stage ovarian cancer patients.

    PubMed

    Minig, Lucas; Zorrero, Cristina; Iserte, Pablo Padilla; Poveda, Andres

    2015-12-26

    Although it is assumed that the combination of chemotherapy and radical surgery should be indicated in all newly diagnosed advanced-stage ovarian cancer patients, one of the main raised questions is how to select the best strategy of initial treatment in this group of patients, neoadjuvant chemotherapy followed by interval debulking surgery or primary debulking surgery followed by adjuvant chemotherapy. The selection criteria to offer one strategy over the other as well as a stepwise patient selection for initial treatment are described. Selecting the best strategy of treatment in newly diagnosed advanced stage ovarian cancer patients is a multifactorial and multidisciplinary decision. Several factors should be taken into consideration: (1) the disease factor, related to the extension and localization of the disease as well as tumor biology; (2) the patient factor, associated with patient age, poor performance status, and co-morbidities; and (3) institutional infrastructure factor, related to the lack of prolonged operative time, an appropriate surgical armamentarium, as well as well-equipped intensive care units with well-trained personnel.

  16. Recent advances in managing chronic HCV infection: focus on therapy in patients with severe liver disease

    PubMed Central

    Maan, Raoel; van der Meer, Adriaan J.

    2016-01-01

    Chronic hepatitis C virus (HCV) infection still represents a major public health problem, as it is thought to be responsible for more than 350,000 deaths around the globe on a yearly basis. Fortunately, successful eradication of the virus has been associated with improved clinical outcome and reduced mortality rates. In the past few years, treatment has improved considerably by the implementation of direct-acting antivirals (DAAs). From 2014 onwards, sofosbuvir, simeprevir, daclatasvir, ledipasvir, paritaprevir, ombitasvir, and dasabuvir have been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Regimens with various combinations of these new drugs, without the use of interferon (IFN), proved to be very effective and well tolerated, even among patients with advanced liver disease. Moreover, treatment duration could be shortened to 12 weeks in the majority of patients. The high costs of these DAAs, however, limit the availability of IFN-free therapy worldwide. Even in wealthy countries, it is deemed necessary to prioritize DAA treatment in order to limit the immediate impact on the health budget. As patients with advanced liver disease are in most need of HCV clearance, many countries decided to treat those patients first. In the current review, we focus on the currently available IFN-free treatment options for patients with cirrhosis. We discuss the virological efficacy as well as the clinical relevance of these regimens among this specific patient population. PMID:27006761

  17. [Efficacy and safety of selective estrogen receptor modulators in patients with advanced chronic kidney disease].

    PubMed

    Nakai, Kentaro

    2016-09-01

    Selective estrogen receptor modulators(SERMs)have beneficial effects on the improvement of bone mineral density of the spine and hip, and decrease the vertebral fracture in postmenopausal women. Similar to patients with advanced chronic kidney disease, including dialysis patients, however, SERMs cannot decrease the risk of hip fracture, which is extremely high in Japanese dialysis patients. One of the most important disadvantages of SERMs is an increase in the risk of venous thromboembolic events and fatal stroke in high-risk groups of the Framingham Stroke Risk Score. On the other hand, SERMs may be used in unique osteoporosis drugs for reducing the incidence and progression of breast cancer. Moreover, SERMs attenuate oxidative stress and may lessen the deterioration of kidney function in patients with chronic kidney disease. The evidences for the efficacy and safety of SERMs in patients with advanced chronic kidney disease are insufficient, and knowledge concerning the selection and indication of osteoporosis drugs for those patients need to be developed. PMID:27561348

  18. Chemotherapy in elderly patients with advanced non-small cell lung cancer.

    PubMed

    Quoix, Elisabeth; Westeel, Virginie; Zalcman, Gérard; Milleron, Bernard

    2011-12-01

    Because of increasing life expectancy and of higher risk of cancer with ageing, lung cancer in elderly is a frequent disease. For a long time nihilism influenced treatment decisions in elderly patients with advanced non-small cell lung cancer. Since the beginning of the last decade single agent chemotherapy has been accepted as standard of care, vinorelbine and gemcitabine being the most frequently used drugs in Europe and US, docetaxel in Japan. Platinum-based doublets have been shown to be superior to monotherapy in young and fit patients with advanced non-small cell lung cancer. Although there were some indications from subgroup analyses of clinical trials not specifically dedicated to elderly patients that a platinum-based doublet might also benefit to older patients, there was no definitive proof of concept until ASCO meeting 2010. At this meeting results of a phase 3 trial showed that PS 0-2 patients, aged 70-89 years drove a significant benefit from a treatment with carboplatin associated to weekly paclitaxel compared to a monotherapy. Thus, the paradigm of treatment in elderly patients should perhaps be modified from a single agent to doublet chemotherapy. Whether other platinum-based doublets would provide the same benefit as the specific one studied remains to be evaluated. PMID:21893363

  19. Advance Directives and Do-Not-Resuscitate Orders in Patients with Cancer with Metastatic Spinal Cord Compression: Advanced Care Planning Implications

    PubMed Central

    Palmer, J. Lynn; Bianty, Josephine; Konzen, Benedict; Shin, Ki; Bruera, Eduardo

    2010-01-01

    Abstract Objectives Communication about end-of-life decisions is crucial. Although patients with metastatic spinal cord compression (MSCC) have a median survival time of 3 to 6 months, few data are available concerning the presence of advance directives and do-not-resuscitate (DNR) orders in this population. The objective of this study was to determine presence of advance directives and DNR order among patients with MSCC. Methods We retrospectively reviewed data concerning advance directives for 88 consecutive patients with cancer who had MSCC and required rehabilitation consultation at The University of Texas M. D. Anderson Cancer Center from September 20, 2005 to August 29, 2008. We characterized the data using univariate descriptive statistics and used the Fisher exact test to find correlations. Results The mean age of this patient population was 55 years (range, 24–81). Thirty patients (33%) were female. Twenty patients (23%) had a living will, 27 patients (31%) had health care proxies, and 10 patients (11%) had either out-of-hospital DNR order and/or dictated DNR note. The median survival time for these patients was 4.3 months. Conclusion Despite strong evidence showing short survival times for MSCC patients, it seems many of these patients are not aware of the urgency to have an advance directive. This may be an indicator of delayed end-of-life palliative care and suboptimal doctor–patient communication. Using the catastrophic event of a diagnosis of MSCC to trigger communication and initiate palliative care may be beneficial to patients and their families. PMID:20192843

  20. Vascularized Free Lymph Node Flap Transfer in Advanced Lymphedema Patient after Axillary Lymph Node Dissection

    PubMed Central

    Cook, Kyung Hoon; Park, Myong Chul; Lim, Seong Yoon; Jung, Yong Sik

    2016-01-01

    Lymphedema is a condition characterized by tissue swelling caused by localized fluid retention. Advanced lymphedema is characterized by irreversible skin fibrosis (stage IIIb) and nonpitting edema, with leather-like skin, skin crypts, and ulcers with or without involvement of the toes (stage IVa and IVb, respectively). Recently, surgical treatment of advanced lymphedema has been a challenging reconstructive modality. Microvascular techniques such as lymphaticovenous anastomosis and vascularized lymph node flap transfer are effective for early stage lymphedema. In this study, we performed a two-stage operation in an advanced lymphedema patient. First, a debulking procedure was performed using liposuction. A vascularized free lymph node flap transfer was then conducted 10 weeks after the first operation. In this case, good results were obtained, with reduced circumferences in various parts of the upper extremity noted immediately postoperation. PMID:27064862

  1. Treating Elderly Patients With Hormone Receptor–Positive Advanced Breast Cancer

    PubMed Central

    Riseberg, David

    2015-01-01

    As the overall population ages, the proportion of elderly patients (aged ≥65 years) with breast cancer also increases. Studies have shown that elderly patients with hormone receptor–positive breast cancer can derive as much benefit from treatment as do younger patients, yet they remain underrepresented in clinical trials and are often undertreated in clinical practice. Treatment decisions for older patients should not be based solely on chronologic age; a patient’s physiologic functioning and comorbidities must also be taken into consideration. For recurrent or metastatic disease, systemic treatment with endocrine therapies or chemotherapy may prolong a patient’s life and alleviate troublesome symptoms. Resistance to therapy remains a problem in the advanced breast cancer setting, with most patients eventually becoming resistant to additional treatment. New combination regimens that target multiple pathways, such as everolimus plus exemestane, have shown efficacy in elderly patients previously resistant to endocrine therapies, and future research may need to focus on such combinations in order to improve outcomes in this patient group. A number of investigational agents are in clinical development, although few studies identify their effects in the elderly patient population. Optimizing effective yet tolerable therapeutic regimens for elderly patients could improve their outcomes while ensuring that the goals of improved survival and quality of life are considered. PMID:26339192

  2. Long-term outcomes of patients with advanced hepatocellular carcinoma who achieved complete remission after sorafenib therapy

    PubMed Central

    2015-01-01

    Background/Aims Sorafenib is currently the sole molecular targeted agent that improves overall survival in advanced hepatocellular carcinoma (HCC). Despite the efficacy of sorafenib, the response rate varies in patients with advanced HCC. We retrospectively analyzed a series of Korean patients with advanced HCC with complete remission (CR) after sorafenib therapy. Methods In total, 523 patients with advanced HCC were treated with sorafenib in 3 large tertiary referral hospitals in Korea. A survey was conducted to collect data on patients who experienced CR after sorafenib monotherapy, and their medical records and follow-up data were analyzed. The tumor response and recurrence rates were assessed by radiologic study, based on modified response evaluation criteria in solid tumors. Results Seven patients with advanced HCC experienced CR after sorafenib therapy. The median time to tumor disappearance and the median disease-free survival time were 3 months and 9 months, respectively. HCC recurrence was identified in three cases (42.9%). Of these, two patients discontinued sorafenib before or after achieving CR and the other patient continued sorafenib after achieving CR. HCC recurred at 3, 10, and 42 months after CR in these three patients. Three patients needed dose reduction for toxicity and adverse events. Conclusions Though CR was achieved after sorafenib therapy in patients with advanced HCC, the recurrence rate was relatively high. Subsequent strategies to reduce a chance of recurrence after sorafenib therapy are required to investigate. PMID:26527250

  3. Long-term levodopa/carbidopa intestinal gel in advanced Parkinson's disease.

    PubMed

    Cáceres-Redondo, María T; Carrillo, Fátima; Lama, María J; Huertas-Fernández, Ismael; Vargas-González, Laura; Carballo, Manuel; Mir, Pablo

    2014-03-01

    The short-term benefits of levodopa/carbidopa intestinal gel (LCIG) in patients with advanced Parkinson's disease (PD) are well documented, but the long-term benefits are still uncertain. The aim of this study was to investigate the motor and cognitive outcome of LCIG treatment in advanced PD after a follow-up period of at least 24 months. We assessed 29 patients with advanced PD who started LCIG infusion at our centre between 2007 and 2013. Motor fluctuations, parkinsonian symptoms, activities of daily living and impact on quality of life were evaluated. We also investigated the cognitive outcome using a battery of neuropsychological tests. All adverse events were recorded. Of the 29 PD patients who initiated LCIG, 16 patients reached the follow-up evaluation (24 months), after a mean time period of 32.2 ± 12.4 months. Six patients did not fulfil the 24-month follow-up visit and were evaluated after a mean time period of 8.6 ± 5.4 months. Seven patients discontinued the treatment before the scheduled visit. "Off" time and "On" dyskinesia duration were significantly reduced. LCIG improved quality of life and non motor symptoms, despite overall unchanged total levodopa doses prior to LCIG beginning. Motor and cognitive decline were detected. A relatively high number of adverse events occurred during the follow-up, above all, technical problems with the infusion device and mild problems related with gastrostomy. There were four cases of peripheral neuropathy (PN), 2 of which were considered serious. Our data confirm that LCIG is beneficial in the long-term treatment of advanced PD patients despite a decline in cognitive functions in a subgroup of patients, probably due to disease progression. PN in patients with LCIG may be more frequent than the published date suggest. PMID:24477490

  4. Advances in the pathogenesis and treatment of patients with stiff person syndrome.

    PubMed

    Dalakas, Marinos C

    2008-01-01

    Advances in the clinical diagnosis, prognosis, pathogenesis, and therapies for stiff person syndrome (SPS), based on observations in more than 50 consecutive patients, are presented. The syndrome varies from mild to severe, but if untreated it can be progressive and disabling. SPS remains a largely underdiagnosed condition. Anti-glutamic acid decarboxylase (GAD) antibodies provide an excellent diagnostic marker, but their role in disease pathogenesis is uncertain. Research focused on identifying new autoantigens has provided evidence that gamma-aminobutyric acid (GABA)(A) receptor-associated protein (GABARAP), a 14-kD protein localized at the postsynaptic regions of GABAergic synapses, is a new antigenic target. In up to 65% of SPS patients, there are circulating anti-GABARAP antibodies that inhibit the GABA(A) receptor expression on GABAergic neurons. This review examines the diagnostic criteria for SPS, SPS variants, common errors in diagnosis, and a step-by-step therapeutic approach, including new advances in therapy.

  5. Religious Coping is Associated with the Quality of Life of Patients with Advanced Cancer

    PubMed Central

    Tarakeshwar, Nalini; Vanderwerker, Lauren C.; Paulk, Elizabeth; Pearce, Michelle J.; Kasl, Stanislav V.; Prigerson, Holly G.

    2008-01-01

    Background For patients confronting a life-threatening illness such as advanced cancer, religious coping can be an important factor influencing their quality of life (QOL). Objective The study's main purpose was to examine the association between religious coping and QOL among 170 patients with advanced cancer. Both positive religious coping (e.g., benevolent religious appraisals) and negative religious coping (e.g., anger at God) and multiple dimensions of QOL (physical, physical symptom, psychological, existential, and support) were studied. Design Structured interviews were conducted with 170 patients recruited as part of an ongoing multi-institutional longitudinal evaluation of the prevalence of mental illness and patterns of mental health service utilization in advanced cancer patients and their primary informal caregivers. Measurements Patients completed measures of QOL (McGill QOL questionnaire), religious coping (Brief Measure of Religious Coping [RCOPE] and Multidimensional Measure of Religion/Spirituality), self-efficacy (General Self-Efficacy Scale), and sociodemographic variables. Results Linear regression analyses revealed that after controlling for sociodemographic variables, lifetime history of depression and self-efficacy, greater use of positive religious coping was associated with better overall QOL as well as higher scores on the existential and support QOL dimensions. Greater use of positive religious coping was also related to more physical symptoms. In contrast, greater use of negative religious coping was related to poorer overall QOL and lower scores on the existential and psychological QOL dimensions. Conclusions Findings show that religious coping plays an important role for the QOL of patients and the types of religious coping strategies used are related to better or poorer QOL. PMID:16752970

  6. End-of-life care in patients with advanced lung cancer.

    PubMed

    Lim, Richard B L

    2016-10-01

    Despite advances in the detection, pathological diagnosis and therapeutics of lung cancer, many patients still develop advanced, incurable and progressively fatal disease. As physicians, the duties to cure sometimes, relieve often and comfort always should be a constant reminder to us of the needs that must be met when caring for a patient with lung cancer. Four key areas of end-of-life care in advanced lung cancer begin with first recognizing 'when a patient is approaching the end of life'. The clinician should be able to recognize when the focus of care needs to shift from an aggressive life-sustaining approach to an approach that helps prepare and support a patient and family members through a period of progressive, inevitable decline. Once the needs are recognized, the second key area is appropriate communication, where the clinician should assist patients and family members in understanding where they are in the disease trajectory and what to expect. This involves developing rapport, breaking bad news, managing expectations and navigating care plans. Subsequently, the third key area is symptom management that focuses on the goals to first and foremost provide comfort and dignity. Symptoms that are common towards the end of life in lung cancer include pain, dyspnoea, delirium and respiratory secretions. Such symptoms need to be anticipated and addressed promptly with appropriate medications and explanations to the patient and family. Lastly, in order for physicians to provide quality end-of-life care, it is necessary to understand the ethical principles applied to end-of-life-care interventions. Misconceptions about euthanasia versus withholding or withdrawing life-sustaining treatments may lead to physician distress and inappropriate decision making. PMID:27585597

  7. Navigating Ethical Conflicts Between Advance Directives and Surrogate Decision-Makers' Interpretations of Patient Wishes.

    PubMed

    Bruce, Courtenay R; Bibler, Trevor; Childress, Andrew M; Stephens, Ashley L; Pena, Adam M; Allen, Nathan G

    2016-02-01

    There is little guidance on what clinicians should do when advance directives (or living wills, specifically) are challenged, particularly when surrogate decision-makers' interpretations of patients' wishes conflict with the living will. In our commentary, we make a controversial argument suggesting that overriding living wills can be ethically preferable to the alternative of strictly adhering to them. We propose four ethical considerations for determining whether it is ethically supportable to override living wills.

  8. Prosthodontic treatment for a patient with advanced hydantoin-associated gingival hyperplasia: a case report.

    PubMed

    Hayakawa, I; Osada, E; Morisawa, M; Nakagawa, Y; Watanabe, I

    1996-04-01

    A patient in whom gingival hyperplasia was caused by prolonged use of an anticonvulsant drug (hydantoin) is described. Advanced gingival hyperplasia and significant displacement of the remaining teeth caused severe damage, especially to the patient's appearance. It was not possible to cure the problems completely with routine periodontal treatment. It was decided to extract all the remaining teeth and restore function and esthetics early with complete dentures. Cephalometric analysis was used to determine the degree to which the teeth had drifted. During fabrication of the dentures, the analysis was very useful in deciding the position of the anterior teeth and checking the vertical dimension of occlusion.

  9. Gross Hematuria and Bladder Tumor in a Patient with Advanced Thyroid Papillary Carcinoma

    PubMed Central

    Matsuo, Yuki; Ikeoka, Toshiyuki; Oba, Kojiro; Miyata, Yasuyoshi; Sakai, Hideki; Abe, Kuniko; Kawakami, Atsushi

    2013-01-01

    We present a 73-year-old female with advanced thyroid papillary carcinoma who complained of gross hematuria. We found a bladder tumor and considered it the cause of her symptom. Cystoscopic findings of the tumor were unusual, with peri-tumor vessel formation. Pathological examination of the bladder tumor was consistent with metastasis of thyroid papillary carcinoma. Therefore, we identified thyroid carcinoma metastasis to the urinary bladder as the cause of hematuria in our patient. Thyroid carcinoma metastasis to the bladder is extremely rare, but it should be included among differential diagnoses for gross hematuria in patients with a clinical history of thyroid carcinoma. PMID:23762664

  10. Intercostal nerves block for mastectomy in two patients with advanced breast malignancy.

    PubMed

    Kolawole, Israel K; Adesina, Michael D; Olaoye, Iyiade O

    2006-03-01

    Regional anesthesia is recognized as an alternative to general anesthesia for modern breast cancer surgery. Various techniques of block have been described. Each has its unique problems. Regional anesthesia was chosen for simple mastectomy in two patients with advanced breast malignancy, due to compromised pulmonary status resulting from widespread malignant infiltration of both lungs. We used intercostal nerves block. The block was supplemented with an infraclavicular infiltration to interrupt the branches of the superficial cervical plexus that provide sensation to the upper chest wall and subcutaneous infiltration in the midline to block the nerve supply from the contralateral side. Anesthesia was generally effective and the operations were uneventful. Both patients and surgeons expressed satisfaction. We conclude that where patients have significant comorbidities that make general anesthesia undesirable, the use of intercostal nerves block remains a safe and reliable anesthetic option that allows the patient access to surgery for simple mastectomy.

  11. Identifying the optimal criteria of radiotherapeutic parameters for patients with unresectable locally advanced hepatocellular carcinoma.

    PubMed

    Son, Seok Hyun; Jang, Hong Seok; Sung, Soo Yoon; Kang, Hye Jin; Lee, Sojung; Kay, Chul Seung

    2015-12-01

    The purpose of this study is to identify the optimal criteria of the radiotherapeutic parameters in patients with unresectable locally advanced hepatocellular carcinoma (HCC). 103 patients were enrolled in this study. All patients received RT delivered using the TomoTherapy Hi-Art system between March 2006 and February 2012. We evaluated the planning target volume (PTV), total dose (Gy10), and NTNL-V(BED20) (non-target normal liver volume receiving more than a biologically effective dose of 20 Gy8) as significant radiotherapeutic parameters associated with hepatic function deterioration and local progression-free survival (PFS). A PTV of 279 cm3 or 304 cm3, a total dose of 60 Gy10, and a NTNL-V(BED20) of 40.8% were identified as the optimal cut-off values of radiotherapeutic parameters to prevent hepatic function deterioration and prolong local PFS. Based on these findings, patients were divided in a favorable and an unfavorable prognosis group. The differences in median local PFS, overall survival, and incidence of deteriorated hepatic function between the two groups were 11.2 months, 11.1 months, and 71.7%, respectively (p < 0.001 in each case). In conclusion, we suggest that the optimal criteria of the radiotherapeutic parameters for patients with unresectable locally advanced HCC are: PTV ≤ 279 cm3, total dose > 60 Gy10, and NTNL-V(BED20) ≤ 40.8%. PMID:26510905

  12. Meaning-centered group psychotherapy for patients with advanced cancer: a pilot randomized controlled trial

    PubMed Central

    Breitbart, William; Rosenfeld, Barry; Gibson, Christopher; Pessin, Hayley; Poppito, Shannon; Nelson, Christian; Tomarken, Alexis; Timm, Anne Kosinski; Berg, Amy; Jacobson, Colleen; Sorger, Brooke; Abbey, Jennifer; Olden, Megan

    2013-01-01

    Objectives An increasingly important concern for clinicians who care for patients at the end of life is their spiritual well-being and sense of meaning and purpose in life. In response to the need for short-term interventions to address spiritual well-being, we developed Meaning Centered Group Psychotherapy (MCGP) to help patients with advanced cancer sustain or enhance a sense of meaning, peace and purpose in their lives, even as they approach the end of life. Methods Patients with advanced (stage III or IV) solid tumor cancers (N = 90) were randomly assigned to either MCGP or a supportive group psychotherapy (SGP). Patients were assessed before and after completing the 8-week intervention, and again 2 months after completion. Outcome assessment included measures of spiritual well-being, meaning, hopelessness, desire for death, optimism/pessimism, anxiety, depression and overall quality of life. Results MCGP resulted in significantly greater improvements in spiritual well-being and a sense of meaning. Treatment gains were even more substantial (based on effect size estimates) at the second follow-up assessment. Improvements in anxiety and desire for death were also significant (and increased over time). There was no significant improvement on any of these variables for patients participating in SGP. Conclusions MCGP appears to be a potentially beneficial intervention for patients’ emotional and spiritual suffering at the end of life. Further research, with larger samples, is clearly needed to better understand the potential benefits of this novel intervention. PMID:19274623

  13. PD-L1 (B7-H1) and PD-1 Pathway Blockade for Cancer Therapy: Mechanisms, Response Biomarkers and Combinations

    PubMed Central

    Zou, Weiping; Wolchok, Jedd D.; Chen, Lieping

    2016-01-01

    PD-L1 and PD-1 (PD) pathway blockade is a highly promising therapy and has elicited durable anti-tumor responses and long-term remissions in a subset of patients with a broad spectrum of cancers. How to improve, widen, and predict the clinical response to anti-PD therapy is a central theme in the field of cancer immunology and immunotherapy. Oncologic, immunologic, genetic and biological studies focused on the human cancer microenvironment have yielded significant insight into this issue. In this Review, we focus on tumor microenvironment; evaluate several potential therapeutic response markers including the PD-L1 and PD-1 expression pattern, genetic mutations within cancer cells and neoantigens, cancer epigenetics and effector T cell landscape, microbiota, and their mechanisms of action and roles in shaping, being shaped and/or predicting therapeutic responses. We also discuss a variety of combinations with PD pathway blockade and their scientific rationales for cancer treatment. PMID:26936508

  14. [Incidence and Risk Assessment of Tumor Lysis Syndrome in Patients with Advanced Germ Cell Cancer].

    PubMed

    Kurobe, Masahiro; Kawai, Koji; Tanaka, Ken; Ichioka, Daishi; Yoshino, Takayuki; Kandori, Shuya; Kawahara, Takashi; Waku, Natsui; Takaoka, Ei-Ichirou; Kojima, Takahiro; Joraku, Akira; Suetomi, Takahiro; Miyazaki, Jun; Nishiyama, Hiroyuki

    2016-05-01

    Tumor lysis syndrome (TLS) is a major oncological emergency. TLS is common in patients with hematological malignancies, but it can occur across a spectrum of cancer types. Germ cell tumors (GCT) have rapid cancer cell turnover and often present with bulky metastasis. The international TLS expert consensus panel has recommended guidelines for a medical decision tree to assign low, intermediate and high risk to patients with cancer at risk for TLS. GCT is classified as intermediate risk for TLS, and the patients who have other TLS risks factors are classified to be at high risk for TLS. In this study, we retrospectively analyzed 67 patients with metastatic GCT who were treated with induction chemotherapy at Tsukuba University Hospital between 2000 and 2013. Thirty-one, 15 and 21 patients were classified with good-, intermediate- and poor-prognosis disease, respectively, according to the International Germ Cell Cancer Collaborative Group criteria. Twelve patients (18%) were classified to be at high risk for TLS, and two patients were treated with allopurinol or rasburicase as prophylaxes for TLS. They did not show progression to laboratory TLS (L-TLS). In the remaining 10 TLS high-risk patients, three (30%) patients developed L-TLS after chemotherapy and started receiving oral allopurinol. As a result, no patients developed clinical TLS (C-TLS). In this study, 30% of TLS-high risk patients developed L-TLS without prophylactic treatment. Therefore, it is important to conduct TLS-risk stratification and consider prophylaxis such as rasburicase for advanced GCT patients at induction chemotherapy. PMID:27320114

  15. Intermittent outpatient nesiritide infusion reduces hospital admissions in patients with advanced heart failure.

    PubMed

    Schwarz, Ernst R; Najam, Sabeen; Akel, Rami; Sulimanjee, Nasir; Bionat, Susan; Rosanio, Salvatore

    2007-09-01

    Recombinant B-type natriuretic peptide (BNP) is a therapeutic modality in patients with decompensated congestive heart failure. Retrospectively tested are the effects of intermittent outpatient nesiritide infusion on symptoms, hospital readmission rates, endogenous BNP, and renal function in patients with advanced heart failure. Twenty-four patients in heart failure in New York Heart Association (NYHA) classes III-IV received a 6- to 8-hour intermittent nesiritide outpatient infusion (0.01 mcg/kg/min continuously intravenously) once weekly for a total duration of 3 months in addition to standard medical therapy. Data were analyzed retrospectively to compare hospital readmission rates, endogenous BNP levels, blood urea nitrogen, and creatinine levels 1 year before and up to 12 months after starting treatment. All patients tolerated nesiritide infusions well with no significant adverse events. At the end of the observation period, NYHA classes had improved 1 class in 16 patients and 2 classes in 4 patients and remained unchanged in 4 patients. There was a significant reduction in hospital readmissions within 1 year with nesiritide treatment compared with the year before (0.94 +/- 0.8 vs 3.6 +/- 2.2, P < .005). No significant changes were seen regarding endogenous BNP levels (1002 +/- 870 vs 1092 +/- 978 pg/mL, P = .95), blood urea nitrogen levels (45 +/- 28 vs 45 +/- 26 mg/dL, P = .96), and a tendency of slightly elevated creatinine levels that did not differ significantly compared with prior levels (1.76 +/- 0.85 vs 1.1 +/- 0.56 mg/dL, P = .5). Intermittent outpatient nesiritide treatment resulted in improved symptoms and reduced hospital readmission rates without a significant decline in renal function in patients with advanced heart failure but did not alter endogenous BNP levels.

  16. The Experiences of Advanced Practice Nurses Caring for Patients with Substance Use Disorder and Chronic Pain.

    PubMed

    St Marie, Barbara

    2016-10-01

    Management of chronic pain is a challenge shared by healthcare providers in various clinical settings. The epidemic of opioid misuse has escalated this challenge. A gap exists in understanding barriers and facilitators to practices of advanced practice registered nurses (APRNs) caring for patients with chronic pain and substance use disorder (SUD). The purpose of this study was to examine the APRNs' experiences while caring for patients with coexisting SUD and chronic pain to help envision better ways to manage pain and direct educational initiatives. Qualitative narrative method. Telephone interviews. Twenty APRNs caring for patients with coexisting SUD and chronic pain were recruited nationwide through the American Society for Pain Management Nursing list serve. Semistructured interviews with thematic analysis. Participants identified 1) a shift of patients from other healthcare providers into the APRNs' practices; 2) barriers to accessing nonmedical modalities for managing pain, including insurance coverage, geographic location, and the patient's desire for only medication management; 3) the role of the APRN in caring for this population contained subthemes of educating and guiding patients through a process of change, applying risk strategies to keep patients safe, and educating colleagues on implementing risk management strategies while prescribing opioids. The APRNs identified barriers to providing care for patients with coexisting SUD and chronic pain. They also described the role of APRNs in providing focused education regarding risk management strategies for assessment, prescribing opioids to manage pain, and minimizing risk. PMID:27567096

  17. Advancing Patient-centered Outcomes in Emergency Diagnostic Imaging: A Research Agenda.

    PubMed

    Kanzaria, Hemal K; McCabe, Aileen M; Meisel, Zachary M; LeBlanc, Annie; Schaffer, Jason T; Bellolio, M Fernanda; Vaughan, William; Merck, Lisa H; Applegate, Kimberly E; Hollander, Judd E; Grudzen, Corita R; Mills, Angela M; Carpenter, Christopher R; Hess, Erik P

    2015-12-01

    Diagnostic imaging is integral to the evaluation of many emergency department (ED) patients. However, relatively little effort has been devoted to patient-centered outcomes research (PCOR) in emergency diagnostic imaging. This article provides background on this topic and the conclusions of the 2015 Academic Emergency Medicine consensus conference PCOR work group regarding "Diagnostic Imaging in the Emergency Department: A Research Agenda to Optimize Utilization." The goal was to determine a prioritized research agenda to establish which outcomes related to emergency diagnostic imaging are most important to patients, caregivers, and other key stakeholders and which methods will most optimally engage patients in the decision to undergo imaging. Case vignettes are used to emphasize these concepts as they relate to a patient's decision to seek care at an ED and the care received there. The authors discuss applicable research methods and approaches such as shared decision-making that could facilitate better integration of patient-centered outcomes and patient-reported outcomes into decisions regarding emergency diagnostic imaging. Finally, based on a modified Delphi process involving members of the PCOR work group, prioritized research questions are proposed to advance the science of patient-centered outcomes in ED diagnostic imaging. PMID:26574729

  18. Efficacy of prophylactic anti-diarrhoeal treatment in patients receiving Campto for advanced colorectal cancer.

    PubMed

    Duffour, J; Gourgou, S; Seitz, J F; Senesse, P; Boutet, O; Castera, D; Kramar, A; Ychou, M

    2002-01-01

    This study assessed the efficacy of combined prophylactic and curative anti-diarrhoeal medication in advanced colorectal patients treated by irinotecan. Thirty-four pre-treated eligible patients were evaluated. There were 44% women, the median age was 65 and 38% of the patients had a 0 performance status. The patients received sucralfate(4g/d) and nifuroxazide(600 mg/d) prophylactic treatment on days 0-7. In the case of severe diarrhoea, preventive treatment was replaced by loperamide(12 mg/d) and diosmectite (9 g/d). Grade 3 delayed diarrhoea occurred in 18% of patients (90% CI: [9.5-28.9]) and 4.6% of cycles. No grade 4 delayed diarrhoea was observed. Twenty-nine patients (85%) received the preventive treatment at cycle 1, while 14% (90% CI: [6.2-25.7]) experienced grade 3 delayed diarrhoea in 3.7% of cycles for a median 4.5 days. The objective response rate was 8% (90% CI [1.4-23.1]) among the 25 assessable patients. Preventive combined treatment is effective in reducing the incidence of severe delayed diarrhoea, and it should be proposed to patients treated with mono-therapy Campto(r) and evaluated in poly-chemotherapy protocols. PMID:12552984

  19. Home Palliative Care for Patients with Advanced Chronic Kidney Disease: Preliminary Results

    PubMed Central

    Teruel, José L.; Rexach, Lourdes; Burguera, Victor; Gomis, Antonio; Fernandez-Lucas, Milagros; Rivera, Maite; Diaz, Alicia; Collazo, Sergio; Liaño, Fernando

    2015-01-01

    Healthcare for patients with advanced chronic kidney disease (ACKD) on conservative treatment very often poses healthcare problems that are difficult to solve. At the end of 2011, we began a program based on the care and monitoring of these patients by Primary Care Teams. ACKD patients who opted for conservative treatment were offered the chance to be cared for mainly at home by the Primary Care doctor and nurse, under the coordination of the Palliative Care Unit and the Nephrology Department. During 2012, 2013, and 2014, 76 patients received treatment in this program (mean age: 81 years; mean Charlson age-comorbidity index: 10, and mean glomerular filtration rate: 12.4 mL/min/1.73 m2). The median patient follow-up time (until death or until 31 December 2014) was 165 days. During this period, 51% of patients did not have to visit the hospital’s emergency department and 58% did not require hospitalization. Forty-eight of the 76 patients died after a median time of 135 days in the program; 24 (50%) died at home. Our experience indicates that with the support of the Palliative Care Unit and the Nephrology Department, ACKD patients who are not dialysis candidates may be monitored at home by Primary Care Teams. PMID:27417813

  20. [Palliative surgery for malignant bowel obstruction in patients with advanced and recurrent gastroenterological cancer].

    PubMed

    Kitani, Kotaro; Yukawa, Masao; Fujiwara, Yoshinori; Tsujie, Masanori; Hara, Joji; Ikeda, Mitsunori; Sato, Katsuaki; Isono, Sayuri; Kawai, Kenji; Miura, Ken; Watatani, Masahiro; Inoue, Masatoshi

    2013-11-01

    We report the outcomes of palliative surgery for the treatment of malignant bowel obstruction in patients with advanced gastroenterological cancer. We studied 20 patients who had undergone palliative surgery over 3 years. We analyzed the clinical findings, surgical procedure, postoperative clinical course, and prognosis. The origin of the patients was colorectal cancer( 9 cases), gastric cancer( 4 cases), uterine cancer( 3 cases), pancreatic cancer( 2 cases), bladder( 1 case), and anal cancer (1 case). Small bowel obstruction was noted in 8 cases and colorectal obstruction was noted in 14 cases. Colostomy was performed in 13 cases, resection and reconstruction were performed in 6 cases, and bypass was performed in 4 cases. Ninety percent of the patients were able to eat solid food following the surgery, but 20% of the patients were forced to have bowel obstruction. The median survival time after palliative surgery was 3 (range, 0-15) months, and 6 patients (30%) died within 2 months. We concluded that palliative surgery for the treatment of malignant bowel obstruction could improve the patients' quality of life. The decision for performing palliative surgery should be made while considering the patient's prognosis, wishes, and potential for symptom improvement. PMID:24393893

  1. Preoperative docetaxel/cisplatin/5-fluorouracil chemotherapy in patients with locally advanced gastro-esophageal adenocarcinoma.

    PubMed

    Bayraktar, Ulas Darda; Bayraktar, Soley; Hosein, Peter; Chen, Emerson; Koniaris, Leonidas G; Rocha-Lima, Caio Max S; Montero, Alberto J

    2012-09-01

    Perioperative chemotherapy plus surgery improves survival compared to surgery alone in GE junctional (GEJ) and gastric adenocarcinomas. The docetaxel/cisplatin/5-fluorouracil (DCF) combination is superior to CF in patients with metastatic gastric cancer. We retrospectively evaluated the safety and efficacy of preoperative DCF chemotherapy in patients with locally advanced gastric and GEJ cancer. Twenty-one gastric and 10 gastroesophageal junctional (GEJ) cancer patients received 2-3 cycles of preoperative docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) on day 1, 5-FU 750 mg/m(2) (continuous infusion) on days 1-5 every 3 weeks. Clinical response was evaluated by comparing pre- and postchemotherapy CT scans. Overall survival (OS) and progression-free survival (PFS) were calculated from the initiation of chemotherapy. None of the patients achieved complete clinical remission while 11 (35%) patients achieved partial clinical remission. Ten patients with GEJ cancer (100%) and 13 with gastric cancer (62%) underwent curative surgery (P = 0.023). Seventeen (55%) patients experienced grade 3-4 chemotherapy-related adverse events. The most common adverse events were anemia, nausea/vomiting, diarrhea, and febrile neutropenia. At a median follow-up of 17.0 months, median OS and PFS were 26.1 months (95% CI: 22.7-29.5) and 18.8 months (95% CI: 9.9-27.7), respectively. The DCF regimen is active in patients with gastric and GEJ adenocarcinoma in the preoperative setting.

  2. PD-L1 blockade for cancer treatment: MEDI4736.

    PubMed

    Ibrahim, Ramy; Stewart, Ross; Shalabi, Aiman

    2015-06-01

    MEDI4736 is a human immunoglobulin (Ig) G1к monoclonal antibody that blocks programmed cell death ligand-1 (PD-L1) binding to its receptors, allowing T cells to recognize and kill tumor cells. Key attributes include high affinity and selectivity for PD-L1, sustained drug exposure for up to 1 year of dosing, and engineering of the antibody to prevent antibody-dependent cell-mediated cytotoxicity. No immunogenicity impacting on the pharmacokinetics/pharmacodynamics of MEDI4736 has been reported at the 10 mg/kg every 2 weeks dose selected for further clinical development. The current safety profile and encouraging early anti-tumor activity of MEDI4736 support further clinical assessment. A broad development program for MEDI4736, both as monotherapy and in combination, is underway across a range of tumor types. This includes a large, multicenter, phase I, dose-escalation/expansion study in solid tumors (with a smaller corresponding study in Japanese patients), a phase I study in myelodysplastic syndrome, and a phase II study in advanced colorectal cancer. In addition, multiple phase I combination studies are ongoing with different agents, including those targeting MEK/BRAF in melanoma, epidermal growth factor receptor, programmed cell death-1, cytotoxic T-lymphocyte antigen-4, OX40, chemokine (C-C motif) receptor 4, and indoleamine 2,3-dioxygenase. Development is most advanced in non-small cell lung cancer, with a program currently comprising four pivotal studies and three phase I combination studies. A pivotal program for MEDI4736 in head and neck cancer began in late 2014. PMID:25965366

  3. Comparison of bevacizumab plus chemotherapy with chemotherapy alone in advanced non-small-lung cancer patients.

    PubMed

    Tang, Ning; Wang, Zhehai

    2016-01-01

    Bevacizumab plus chemotherapy was approved by the US Food and Drug Administration (FDA) as a first-line treatment for advanced nonsquamous, non-small-cell lung cancer (NSCLC) in 2006. This study retrospectively compared the efficacy of bevacizumab plus chemotherapy with chemotherapy alone as the first-line and second-line treatment as well as the maintenance treatment for advanced NSCLC patients. A total of 1,352 patients were included and we analyzed the efficacy evaluation according to the criteria of the Response Evaluation Criteria In Solid Tumors (RECIST), survival, and adverse reactions. The data showed that for bevacizumab plus chemotherapy as the first-line treatment, the median progression-free survival (mPFS) and median overall survival (mOS) were 11.5 and 17.0 months, respectively, compared to 7.0 and 14 months, respectively, in patients who received chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as maintenance treatment, the mPFS and mOS were 6.0 and 17.4 months, respectively, compared to 3.0 and 15.0 months, respectively, with chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as the second-line treatment, the mPFS was 3.0 months compared to only 2.0 months with chemotherapy alone (P<0.01). The overall responses to the different regimens showed that the remission rate with bevacizumab plus chemotherapy was higher than that with chemotherapy alone (31.8% vs 25.5%, P<0.05), although there was no statistical difference in the disease control rate with either first- or second-line treatment. In conclusion, chemotherapy plus bevacizumab as the first-line and maintenance treatment, led to better curative rates and tolerable adverse reactions compared with chemotherapy alone in advanced NSCLC patients. Bevacizumab combined with cytotoxic drugs was suitable as the second-line treatment for such patients.

  4. Comparison of bevacizumab plus chemotherapy with chemotherapy alone in advanced non-small-lung cancer patients.

    PubMed

    Tang, Ning; Wang, Zhehai

    2016-01-01

    Bevacizumab plus chemotherapy was approved by the US Food and Drug Administration (FDA) as a first-line treatment for advanced nonsquamous, non-small-cell lung cancer (NSCLC) in 2006. This study retrospectively compared the efficacy of bevacizumab plus chemotherapy with chemotherapy alone as the first-line and second-line treatment as well as the maintenance treatment for advanced NSCLC patients. A total of 1,352 patients were included and we analyzed the efficacy evaluation according to the criteria of the Response Evaluation Criteria In Solid Tumors (RECIST), survival, and adverse reactions. The data showed that for bevacizumab plus chemotherapy as the first-line treatment, the median progression-free survival (mPFS) and median overall survival (mOS) were 11.5 and 17.0 months, respectively, compared to 7.0 and 14 months, respectively, in patients who received chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as maintenance treatment, the mPFS and mOS were 6.0 and 17.4 months, respectively, compared to 3.0 and 15.0 months, respectively, with chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as the second-line treatment, the mPFS was 3.0 months compared to only 2.0 months with chemotherapy alone (P<0.01). The overall responses to the different regimens showed that the remission rate with bevacizumab plus chemotherapy was higher than that with chemotherapy alone (31.8% vs 25.5%, P<0.05), although there was no statistical difference in the disease control rate with either first- or second-line treatment. In conclusion, chemotherapy plus bevacizumab as the first-line and maintenance treatment, led to better curative rates and tolerable adverse reactions compared with chemotherapy alone in advanced NSCLC patients. Bevacizumab combined with cytotoxic drugs was suitable as the second-line treatment for such patients. PMID:27536131

  5. A Phase II Trial of the Proteasome Inhibitor Bortezomib in Patients with Advanced Biliary Tract Cancers*

    PubMed Central

    Denlinger, Crystal S.; Meropol, Neal J.; Li, Tianyu; Lewis, Nancy L.; Engstrom, Paul F.; Weiner, Louis M.; Cheng, Jonathan D.; Alpaugh, R. Katherine; Cooper, Harry; Wright, John J.; Cohen, Steven J.

    2014-01-01

    Background Patients with advanced biliary tract cancers have limited therapeutic options. Preclinical data suggest proteasome inhibition may be an effective therapeutic strategy. We thus evaluated the clinical efficacy of bortezomib in advanced biliary tract cancers. Patients and Methods Patients with locally advanced or metastatic cholangiocarcinoma or gallbladder adenocarcinoma who had received 0–2 prior therapies received bortezomib 1.3 mg/m2 days 1, 4, 8, and 11 of a 21-day cycle. The primary endpoint was objective response rate. A Simon two-stage design was employed (null response rate of < 5% and response rate of ≥ 20% of interest). Results Twenty patients enrolled: bile duct/gallbladder cancer (14/6), prior treatments 0/1/2 (10/6/3). The trial was discontinued early due to lack of confirmed partial responses. No unanticipated adverse events were noted. There was one unconfirmed partial response. Ten patients achieved stable disease as best response. Median time to progression was 5.8 months (95% CI 0.7–77.6 months). Median survival was 9 months (95% CI 4.6–18.5 months). The 6-month and 1-year survival rates were 70% and 38%. There was no difference in survival based on primary disease site. Conclusions Single agent bortezomib does not result in objective responses in biliary tract cancers. However, the rate of stable disease and time to progression benchmark is encouraging. Further development of bortezomib in combination with other therapies in this disease setting should be considered. PMID:24512954

  6. A sequential study of serum bacterial DNA in patients with advanced cirrhosis and ascites.

    PubMed

    Francés, Rubén; Benlloch, Susana; Zapater, Pedro; González, José M; Lozano, Beatriz; Muñoz, Carlos; Pascual, Sonia; Casellas, Juan A; Uceda, Francisco; Palazón, José M; Carnicer, Fernando; Pérez-Mateo, Miguel; Such, José

    2004-02-01

    Bacterial translocation is currently considered the main pathogenic mechanism leading to spontaneous bacterial peritonitis in patients with advanced cirrhosis and ascites. However, to the authors' knowledge there is no information regarding the characteristics of this process in humans. The goals of the current study were to pursue partially identified bacterial DNA in blood (what the authors consider molecular evidence of bacterial translocation) through its relative quantification in a 72-hour study period by using real-time polymerase chain reaction (PCR). A consecutive series of 17 patients with advanced cirrhosis and culture-negative, nonneutrocytic ascites were studied. Therapeutic paracentesis was performed at the time of admission, and blood samples were obtained at baseline and every 8 hours in a 3-day period. Bacterial DNA was detected by a PCR-based method, relatively quantified by real-time PCR, and identified by automated nucleotide sequencing. Seven of 17 patients demonstrated the simultaneous presence of bacterial DNA in blood and ascitic fluid at the time of admission. After therapeutic paracentesis was performed, bacterial DNA persisted in the blood for a minimum of 24 hours, and was reported to last as long as 72 hours in some patients. In addition, different patterns of bacterial DNA appearance and clearance from the blood were identified. The nucleotide sequencing process demonstrated that bacteria detected in the first sample were identical to those noted in subsequent detections over time. In conclusion, bacterial translocation is a single-species, dynamic process that appears to develop in a subgroup of patients with advanced cirrhosis.

  7. Comparison of bevacizumab plus chemotherapy with chemotherapy alone in advanced non-small-lung cancer patients

    PubMed Central

    Tang, Ning; Wang, Zhehai

    2016-01-01

    Bevacizumab plus chemotherapy was approved by the US Food and Drug Administration (FDA) as a first-line treatment for advanced nonsquamous, non-small-cell lung cancer (NSCLC) in 2006. This study retrospectively compared the efficacy of bevacizumab plus chemotherapy with chemotherapy alone as the first-line and second-line treatment as well as the maintenance treatment for advanced NSCLC patients. A total of 1,352 patients were included and we analyzed the efficacy evaluation according to the criteria of the Response Evaluation Criteria In Solid Tumors (RECIST), survival, and adverse reactions. The data showed that for bevacizumab plus chemotherapy as the first-line treatment, the median progression-free survival (mPFS) and median overall survival (mOS) were 11.5 and 17.0 months, respectively, compared to 7.0 and 14 months, respectively, in patients who received chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as maintenance treatment, the mPFS and mOS were 6.0 and 17.4 months, respectively, compared to 3.0 and 15.0 months, respectively, with chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as the second-line treatment, the mPFS was 3.0 months compared to only 2.0 months with chemotherapy alone (P<0.01). The overall responses to the different regimens showed that the remission rate with bevacizumab plus chemotherapy was higher than that with chemotherapy alone (31.8% vs 25.5%, P<0.05), although there was no statistical difference in the disease control rate with either first- or second-line treatment. In conclusion, chemotherapy plus bevacizumab as the first-line and maintenance treatment, led to better curative rates and tolerable adverse reactions compared with chemotherapy alone in advanced NSCLC patients. Bevacizumab combined with cytotoxic drugs was suitable as the second-line treatment for such patients. PMID:27536131

  8. Age Disparity in Palliative Radiation Therapy Among Patients With Advanced Cancer

    SciTech Connect

    Wong, Jonathan; Xu, Beibei; Yeung, Heidi N.; Roeland, Eric J.; Martinez, Maria Elena; Le, Quynh-Thu; Mell, Loren K.; Murphy, James D.

    2014-09-01

    Purpose/Objective: Palliative radiation therapy represents an important treatment option among patients with advanced cancer, although research shows decreased use among older patients. This study evaluated age-related patterns of palliative radiation use among an elderly Medicare population. Methods and Materials: We identified 63,221 patients with metastatic lung, breast, prostate, or colorectal cancer diagnosed between 2000 and 2007 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Receipt of palliative radiation therapy was extracted from Medicare claims. Multivariate Poisson regression analysis determined residual age-related disparity in the receipt of palliative radiation therapy after controlling for confounding covariates including age-related differences in patient and demographic covariates, length of life, and patient preferences for aggressive cancer therapy. Results: The use of radiation decreased steadily with increasing patient age. Forty-two percent of patients aged 66 to 69 received palliative radiation therapy. Rates of palliative radiation decreased to 38%, 32%, 24%, and 14% among patients aged 70 to 74, 75 to 79, 80 to 84, and over 85, respectively. Multivariate analysis found that confounding covariates attenuated these findings, although the decreased relative rate of palliative radiation therapy among the elderly remained clinically and statistically significant. On multivariate analysis, compared to patients 66 to 69 years old, those aged 70 to 74, 75 to 79, 80 to 84, and over 85 had a 7%, 15%, 25%, and 44% decreased rate of receiving palliative radiation, respectively (all P<.0001). Conclusions: Age disparity with palliative radiation therapy exists among older cancer patients. Further research should strive to identify barriers to palliative radiation among the elderly, and extra effort should be made to give older patients the opportunity to receive this quality of life-enhancing treatment at the end

  9. Incidence and Predictors of 30-Day Readmission Among Patients Hospitalized for Advanced Liver Disease

    PubMed Central

    BERMAN, KENNETH; TANDRA, SWETA; FORSSELL, KATE; VUPPALANCHI, RAJ; BURTON, JAMES R.; NGUYEN, JAMES; MULLIS, DEVONNE; KWO, PAUL; CHALASANI, NAGA

    2011-01-01

    BACKGROUND & AIMS The rate of readmission to the hospital 30 days after discharge (30-day readmission rate) is used as a quality measure for hospitalized patients, but it has not been studied adequately for patients with advanced liver disease. We investigated the incidence and factors that predict this rate and its relationship with mortality at 90 days. METHODS We analyzed data from patients with advanced liver disease who were hospitalized to an inpatient hepatology service at 2 large academic medical centers in 2008. Patients with elective admission and recipients of liver transplants were not included. During the study period, there were 447 patients and a total of 554 eligible admissions. Multivariate analyses were performed to identify variables associated with 30-day readmission and to examine its relationship with mortality at 90 days. RESULTS The 30-day readmission rate was 20%. After adjusting for multiple covariates, readmission within 30 days was associated independently with model for end-stage liver disease scores at discharge (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02–1.09; P = .002), the presence of diabetes (OR, 1.78; 95% CI, 1.07–2.95; P = .027), and male sex (OR, 1.73; 95% CI, 1.03–2.89; P = .038). After adjusting for age, sex, and model for end-stage liver disease score at discharge, the 90-day mortality rate was significantly higher among patients who were readmitted to the hospital within 30 days than those who were not (26.8% vs 9.8%; OR, 2.6; 95% CI, 1.36 –5.02; P = .004). CONCLUSIONS Patients with advanced liver disease frequently are readmitted to the hospital within 30 days after discharge; these patients have a higher 90-day mortality rate than those who are not readmitted in 30 days. These data might be used to develop strategies to reduce early readmission of hospitalized patients with cirrhosis. PMID:21092762

  10. Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies.

    PubMed

    Beck, Bodo B; Baasner, Anne; Buescher, Anja; Habbig, Sandra; Reintjes, Nadine; Kemper, Markus J; Sikora, Przemyslaw; Mache, Christoph; Pohl, Martin; Stahl, Mirjam; Toenshoff, Burkhard; Pape, Lars; Fehrenbach, Henry; Jacob, Dorrit E; Grohe, Bernd; Wolf, Matthias T; Nürnberg, Gudrun; Yigit, Gökhan; Salido, Eduardo C; Hoppe, Bernd

    2013-02-01

    Identification of mutations in the HOGA1 gene as the cause of autosomal recessive primary hyperoxaluria (PH) type III has revitalized research in the field of PH and related stone disease. In contrast to the well-characterized entities of PH type I and type II, the pathophysiology and prevalence of type III is largely unknown. In this study, we analyzed a large cohort of subjects previously tested negative for type I/II by complete HOGA1 sequencing. Seven distinct mutations, among them four novel, were found in 15 patients. In patients of non-consanguineous European descent the previously reported c.700+5G>T splice-site mutation was predominant and represents a potential founder mutation, while in consanguineous families private homozygous mutations were identified throughout the gene. Furthermore, we identified a family where a homozygous mutation in HOGA1 (p.P190L) segregated in two siblings with an additional AGXT mutation (p.D201E). The two girls exhibiting triallelic inheritance presented a more severe phenotype than their only mildly affected p.P190L homozygous father. In silico analysis of five mutations reveals that HOGA1 deficiency is causing type III, yet reduced HOGA1 expression or aberrant subcellular protein targeting is unlikely to be the responsible pathomechanism. Our results strongly suggest HOGA1 as a major cause of PH, indicate a greater genetic heterogeneity of hyperoxaluria, and point to a favorable outcome of type III in the context of PH despite incomplete or absent biochemical remission. Multiallelic inheritance could have implications for genetic testing strategies and might represent an unrecognized mechanism for phenotype variability in PH.

  11. Mechanisms Underpinning Increased Plasma Creatinine Levels in Patients Receiving Vemurafenib for Advanced Melanoma

    PubMed Central

    Hurabielle, Charlotte; Pillebout, Evangéline; Stehlé, Thomas; Pagès, Cécile; Roux, Jennifer; Schneider, Pierre; Chevret, Sylvie; Chaffaut, Cendrine; Boutten, Anne; Mourah, Samia; Basset-Seguin, Nicole; Vidal-Petiot, Emmanuelle; Lebbé, Céleste; Flamant, Martin

    2016-01-01

    Context Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known. Objective We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma. Methods We performed a retrospective monocentric study including consecutive patients treated with Vemurafenib for an advanced melanoma. We collected clinical and biological data concerning renal function before introduction of Vemurafenib and in the course of monthly follow-up visits from March 2013 to December 2014. Cystatin C-derived glomerular filtration rate was evaluated before and after Vemurafenib initiation, as increase in serum cystatin C is specific to a decrease in the glomerular filtration rate. We also performed thorough renal explorations in 3 patients, with measurement of tubular secretion of creatinine before and after Vemurafenib initiation and a renal biopsy in 2 patients. Results 70 patients were included: 97% of them displayed an immediate, and thereafter stable, increase in creatinine (+22.8%) after Vemurafenib initiation. In 44/52 patients in whom Vemurafenib was discontinued, creatinine levels returned to baseline. Serum cystatin C increased, although proportionally less than serum creatinine, showing that creatinine increase under vemurafenib was indeed partly due to a renal function impairment. In addition, renal explorations demonstrated that Vemurafenib induced an inhibition of creatinine tubular secretion. Conclusion Thus, Vemurafenib induces a dual mechanism of increase in plasma creatinine with both an inhibition of creatinine tubular secretion and slight renal function impairment. However, this side effect is mostly reversible when Vemurafenib is discontinued, and should not lead physicians to discontinue the treatment if it is effective. PMID:26930506

  12. EXCESS MORTALITY IN PATIENTS WITH ADVANCED CHRONIC HEPATITIS C TREATED WITH LONG-TERM PEGINTERFERON

    PubMed Central

    Di Bisceglie, Adrian M.; Stoddard, Anne M.; Dienstag, Jules L.; Shiffman, Mitchell L.; Seeff, Leonard B.; Bonkovsky, Herbert L.; Morishima, Chihiro; Wright, Elizabeth C.; Snow, Kristin K.; Lee, William M.; Fontana, Robert J.; Morgan, Timothy R.; Ghany, Marc G.

    2011-01-01

    Background/Aims Chronic hepatitis C virus infection can cause chronic liver disease, cirrhosis and liver cancer. The HALT-C Trial was a prospective, randomized controlled study of long-term, low-dose peginterferon therapy in patients with advanced chronic hepatitis C who had failed to respond to a previous course of optimal antiviral therapy. The aim of this follow-up analysis was to describe the frequency and causes of death among this cohort of patients. Methods Deaths occurring during and after the HALT-C Trial were reviewed by a committee of investigators to determine the cause of death and to categorize each death as liver- or non-liver-related and as related or not to complications of peginterferon. Rates of liver transplantation were also assessed. Results Over a median of 5.7 years, 122 deaths occurred among 1,050 randomized patients (12%) of which 76 were considered liver-related (62%) and 46 non-liver-related (38%); 74 patients (7%) underwent liver transplantation. At 7 years, the cumulative mortality rate was higher in the treatment compared to the control group (20% versus 15%, p=0.049); the primary difference in mortality was in patients in the fibrosis compared to the cirrhosis stratum (14% versus 7%, p=0.01); comparable differences were observed when liver transplantation was included. Excess mortality, emerging after 3 years of treatment, was related largely to non-liver-related death; liver-related mortality was similar in the treatment and control groups. No specific cause of death accounted for the excess mortality, and only one death was suspected to be a direct complication of peginterferon. Conclusions Long-term maintenance peginterferon in patients with advanced chronic hepatitis C is associated with an excess overall mortality, which was primarily due to non-liver-related causes among patients with bridging fibrosis. PMID:21480316

  13. PD-L1 and PD-L2 differ in their molecular mechanisms of interaction with PD-1

    PubMed Central

    Ghiotto, Marguerite; Gauthier, Laurent; Serriari, Nacer; Pastor, Sonia; Truneh, Alemseged; Nunès, Jacques; Olive, Daniel

    2010-01-01

    SUMMARY The programmed death-1 (PD-1) molecule is involved in peripheral tolerance and in the immune escape mechanisms during chronic viral infections and cancer. PD-1 interacts with two ligands, PD-L1 and PD-L2. We have investigated, the molecular mechanisms of PD-1 interactions with its ligands by surface plasmon resonance and cell surface binding as well as the ability of the two ligands to compete for PD-1 binding. PD-L1 and PD-L2 bound PD-1 with comparable affinities, but striking differences were observed at the level of the association and dissociation characteristics. PD-L1, but not PD-L2 had a delayed interaction reminiscent of a phenomenom of conformational transition. These mechanisms were confirmed by using PD-L1 mAbs that delayed the dissociation of PD-L1 from PD-1. This mechanism was not restricted to PD-1 binding since PD-L1 behaved in a similar manner with its second ligand, CD80. Finally, we could demonstrate that PD-L1 and PD-L2 competed for PD-1 binding and conversely, an antagonist PD-1 mAb blocked both PD-L1 and PD-L2 binding to PD-1 and strongly enhanced T cell proliferation. These data further emphasize the differential molecular mechanisms of interaction of PD-L1 and PD-L2 with PD-1, and suggest possible new approach for the therapy of chronic infection, cancer and transplantation. PMID:20587542

  14. Distribution of KRAS and BRAF mutations in Moroccan patients with advanced colorectal cancer.

    PubMed

    Marchoudi, N; Amrani Hassani Joutei, H; Jouali, F; Fekkak, J; Rhaissi, H

    2013-12-01

    Targeted therapies have an increasing importance in digestive oncology. To our knowledge, we are the first to report the distribution of KRAS and BRAF mutations in Moroccan patients with advanced colorectal cancer (CRC) in order to introduce targeted therapy in the arsenal of therapeutic modalities for management of this cancer in Morocco. In this study, 92 samples obtained from patients with CRC were tested for the presence of the nine most common mutations in the KRAS gene and BRAF gene. Among the tested patients, 76.09% of patients had wt-KRAS genotype and 23.91% were KRAS mutants and the majority of mutations would result in an amino acid substitution of glycine by aspartic acid (68.2%) The predominant mutations are G>A transitions and G>T transversions. Around 5% (5.43%) of the tested patients bore the V600E mutation in BRAF gene. Only one patient showing to have the V600E mutation in BRAF was also mutated-KRAS. Summing up the results about the KRAS and the BRAF mutation carriers from our study, the portion of potentially non responsive patients for the anti-EGFR treatment is 28.26%.

  15. 89Zr-cetuximab PET imaging in patients with advanced colorectal cancer

    PubMed Central

    Huisman, Marc C.; Vugts, Danielle J.; Roth, Chantal; Luik, Anne Marije; Mulder, Emma R.; Schuit, Robert C.; Boellaard, Ronald; Hoekstra, Otto S.; van Dongen, Guus AMS; Verheul, Henk M.W.

    2015-01-01

    Monoclonal antibodies (mAbs) against the epidermal growth factor receptor (EGFR) are used in the treatment of advanced colorectal cancer (mCRC). Approximately 50% of patients benefit despite patient selection for RAS wild type (wt) tumors. Based on the hypothesis that tumor targeting is required for clinical benefit of anti-EGFR treatment, biodistribution and tumor uptake of 89Zr-cetuximab by Positron Emission Tomography (PET), combining the sensitivity of PET with the specificity of cetuximab for EGFR was evaluated. Ten patients with wt K-RAS mCRC received 37 ± 1 MBq 89Zr-cetuximab directly (<2 h) after the first therapeutic dose of cetuximab. PET-scans were performed from 1 hour to 10 days post injection (p.i.). Biodistribution was determined for blood and organs. Uptake in tumor lesions was quantified by Standardized Uptake Value (SUV) and related to response. In 6 of 10 patients 89Zr-cetuximab uptake in tumor lesions was detected. Four of 6 patients with 89Zr-cetuximab uptake had clinical benefit, while progressive disease was observed in 3 of 4 patients without 89Zr-cetuximab uptake. Taken together, tumor uptake of 89Zr-cetuximab can be visualized by PET imaging. The strong relation between uptake and response warrants further clinical validation as an innovative selection method for cetuximab treatment in patients with wt RAS mCRC. PMID:26309164

  16. 89Zr-cetuximab PET imaging in patients with advanced colorectal cancer.

    PubMed

    Menke-van der Houven van Oordt, Catharina Willemien; Gootjes, Elske C; Huisman, Marc C; Vugts, Danielle J; Roth, Chantal; Luik, Anne Marije; Mulder, Emma R; Schuit, Robert C; Boellaard, Ronald; Hoekstra, Otto S; van Dongen, Guus Ams; Verheul, Henk M W

    2015-10-01

    Monoclonal antibodies (mAbs) against the epidermal growth factor receptor (EGFR) are used in the treatment of advanced colorectal cancer (mCRC). Approximately 50% of patients benefit despite patient selection for RAS wild type (wt) tumors. Based on the hypothesis that tumor targeting is required for clinical benefit of anti-EGFR treatment, biodistribution and tumor uptake of (89)Zr-cetuximab by Positron Emission Tomography (PET), combining the sensitivity of PET with the specificity of cetuximab for EGFR was evaluated. Ten patients with wt K-RAS mCRC received 37 ± 1 MBq (89)Zr-cetuximab directly (<2 h) after the first therapeutic dose of cetuximab. PET-scans were performed from 1 hour to 10 days post injection (p.i.). Biodistribution was determined for blood and organs. Uptake in tumor lesions was quantified by Standardized Uptake Value (SUV) and related to response. In 6 of 10 patients (89)Zr-cetuximab uptake in tumor lesions was detected. Four of 6 patients with (89)Zr-cetuximab uptake had clinical benefit, while progressive disease was observed in 3 of 4 patients without (89)Zr-cetuximab uptake. Taken together, tumor uptake of 89Zr-cetuximab can be visualized by PET imaging. The strong relation between uptake and response warrants further clinical validation as an innovative selection method for cetuximab treatment in patients with wt RAS mCRC.

  17. Cancer Related Fatigue and Quality of Life in Patients with Advanced Prostate Cancer Undergoing Chemotherapy

    PubMed Central

    Charalambous, Andreas; Kouta, Christiana

    2016-01-01

    Cancer related fatigue (CRF) is a common and debilitating symptom that can influence quality of life (QoL) in cancer patients. The increase in survival times stresses for a better understanding of how CRF affects patients' QoL. This was a cross-sectional descriptive study with 148 randomly recruited prostate cancer patients aiming to explore CRF and its impact on QoL. Assessments included the Cancer Fatigue Scale, EORTC QLQ-C30, and EORTC QLQ-PR25. Additionally, 15 in-depth structured interviews were performed. Quantitative data were analyzed with simple and multiple regression analysis and independent samples t-test. Qualitative data were analyzed with the use of thematic content analysis. The 66.9% of the patients experienced CRF with higher levels being recorded for the affective subscale. Statistically significant differences were found between the patients reporting CRF and lower levels of QoL (mean = 49.1) and those that did not report fatigue and had higher levels of QoL (mean = 72.1). The interviews emphasized CRF's profound impact on the patients' lives that was reflected on the following themes: “dependency on others,” “loss of power over decision making,” and “daily living disruption.” Cancer related fatigue is a significant problem for patients with advanced prostate cancer and one that affects their QoL in various ways. PMID:26981530

  18. Health, economic, psychological and social impact of educating carers of patients with advanced pulmonary disease (protocol).

    PubMed

    Sladek, R M; Jones, T; Phillips, P A; Luszcz, M; Rowett, D; Eckermann, S; Woodman, R J; Frith, P

    2011-09-01

    People with advanced pulmonary disease (APD), such as those with chronic obstructive pulmonary disease, have markedly impaired quality of life. Home Oxygen Therapy (HOT) itself is burdensome, although it often improves survival duration and quality of life in these patients. The exact burdens on informal caregivers of these patients are unknown. The central purpose of the pragmatic randomized controlled study described in this protocol is to determine the effectiveness of improving the skills and knowledge of carers of patients with APD who use HOT. Specifically we aimed to estimate the incremental impact of this carer intervention above usual care on health, economic, psychological and social domains for patient and carer dyads relative to the level of current burden. Eligible patients and their carers were recruited through three major hospitals, and randomized to an intervention or control group. The carers in the intervention group received two home-delivered education sessions based on the principles of academic detailing. Participants are currently being followed over 12 months. The primary outcome will be the proportion of patients surviving without a chronic obstructive pulmonary disease-related readmission / residential (non respite) care over 12 months. Carer secondary outcomes include perceived caregiver burden, level of expected and received social support, perceived level of mastery, self esteem, health related quality of life and disability, and ability to conduct domestic chores and household maintenance, social activities and provide service to others, and fatigue. Secondary patient outcomes include health related quality of life and disability, and current respiratory health status.

  19. Evaluation of ExPress glaucoma filtration device in Indian patients with advanced glaucoma.

    PubMed

    Angmo, Dewang; Sharma, Reetika; Temkar, Shreyas; Dada, Tanuj

    2015-05-01

    ExPress glaucoma filtration device (GFD) has recently become available in India as a surgical option for glaucoma patients. We retrospectively evaluated the outcome of ExPress GFD in 12 eyes with advanced glaucoma with intraocular pressures (IOPs) not controlled on maximal tolerable medical therapy. The mean preoperative IOP of 29.58 ± 7.13 mmHg decreased to 17.0 ± 2.67 and 17.40 ± 0.89 mmHg at 6 and 12 months after surgery. Absolute success (IOP ≤ 18 mmHg, with no additional glaucoma medications) was achieved in eight cases (66.7%) and qualified success (IOP ≤ 18 mmHg, with additional glaucoma medications) in two cases (16.7%) at 1-year after surgery. Early intervention was needed in 4 patients; two underwent anterior chamber reformation while the other two required needling. Two patients required resurgery. There was no significant change in the best corrected visual acuity postoperatively (P = 0.37). ExPress GFD does not seem to offer a benefit over standard trabeculectomy in patients with advanced glaucomatous disease in terms of IOP control or complication rate. However, due to the small sample size with a heterogeneous mixture of primary and secondary glaucoma's, we await further studies with a larger sample size and long-term follow-up, to see how the device performs.

  20. Assessment of anxiety and depression in advanced cancer patients and their relationship with quality of life.

    PubMed

    Mystakidou, K; Tsilika, E; Parpa, E; Katsouda, E; Galanos, A; Vlahos, L

    2005-10-01

    The growing interest in the mental health and quality of life of cancer patients, has been the major reason for conducting this study. The aims were to compare advanced cancer patients' responses to Hospital Anxiety and Depression (HAD) scale with those to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30, version 3.0), as well as the impact of quality of life dimensions (as measured by EORTC QLQ-C30) on the levels of anxiety and depression. The analysis, conducted in 120 advanced cancer patients, showed that the most significant associations were found between emotional functioning and HAD-T (total sum of scores) (r=-0.747; p < 0.0005), HAD-A (anxiety) (r=-0.725; p < 0.0005) and HAD-D (depression) (r=-0.553; p < 0.0005). In the prediction of HAD-T, the contribution of physical, emotional, role, and social functioning along with nausea-vomiting, dyspnea, sleep disturbance and gender is high. For anxiety, the predictor variables were physical, role, cognitive, emotional, and social functioning, followed by dyspnea, sleep disturbance, and appetite loss, while depression was predicted by physical, role, emotional, and social functioning, the symptoms of nausea-vomiting, pain, sleep disturbance, constipation, as well as the variables of age, gender, anticancer treatment and performance status. Concluding, psychological morbidity, in this patient population, was predominantly predicted by the emotional functioning dimension of EORTC QLQ-C30. PMID:16155770

  1. Evaluation of ExPress glaucoma filtration device in Indian patients with advanced glaucoma

    PubMed Central

    Angmo, Dewang; Sharma, Reetika; Temkar, Shreyas; Dada, Tanuj

    2015-01-01

    ExPress glaucoma filtration device (GFD) has recently become available in India as a surgical option for glaucoma patients. We retrospectively evaluated the outcome of ExPress GFD in 12 eyes with advanced glaucoma with intraocular pressures (IOPs) not controlled on maximal tolerable medical therapy. The mean preoperative IOP of 29.58 ± 7.13 mmHg decreased to 17.0 ± 2.67 and 17.40 ± 0.89 mmHg at 6 and 12 months after surgery. Absolute success (IOP ≤ 18 mmHg, with no additional glaucoma medications) was achieved in eight cases (66.7%) and qualified success (IOP ≤ 18 mmHg, with additional glaucoma medications) in two cases (16.7%) at 1-year after surgery. Early intervention was needed in 4 patients; two underwent anterior chamber reformation while the other two required needling. Two patients required resurgery. There was no significant change in the best corrected visual acuity postoperatively (P = 0.37). ExPress GFD does not seem to offer a benefit over standard trabeculectomy in patients with advanced glaucomatous disease in terms of IOP control or complication rate. However, due to the small sample size with a heterogeneous mixture of primary and secondary glaucoma's, we await further studies with a larger sample size and long-term follow-up, to see how the device performs. PMID:26139813

  2. Current therapeutic strategies of anti-HER2 treatment in advanced breast cancer patients

    PubMed Central

    Nowara, Elżbieta

    2016-01-01

    The HER2/neu (ERBB2) oncogene is amplified and/or overexpressed in approximately 20% of breast cancers, and is a strong prognostic factor for relapse and poor overall survival, particularly in node-positive patients. It is also an important predictor for response to trastuzumab, which has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. Treatment with the anti-HER2 humanized monoclonal antibody – trastuzumab significantly improves progression-free and overall survival among patients with HER2-positive breast cancer. However, in most patients with HER2-positive metastatic breast cancer, the disease progresses occurred, what cause the need for new targeted therapies for advanced disease. In clinical trials, there are tested new drugs to improve the results of treatment for this group of patients. This paper presents new drugs introduced into clinical practice for treatment of advanced breast cancer, whose molecular target are receptors of the HER2 family. In addition, new therapeutic strategies and drugs that are currently in clinical researches are discussed. PMID:27095932

  3. Needs of family caregivers of advanced cancer patients: a survey in Shanghai of China.

    PubMed

    Cui, J; Song, L J; Zhou, L J; Meng, H; Zhao, J J

    2014-07-01

    It is important to understand the unmet needs of family caregivers of advanced cancer patients for developing and refining services to address the identified gaps in cancer care. To explore their needs in Chinese mainland and the possible factors associated with their needs, a self-developed questionnaire was used to survey a sample of 649 participants in 15 hospitals of Shanghai. The data were analysed using descriptive statistics, factor analysis, t-test, one-way ANOVA, and Fishers least significant difference t-test. All statistical analyses were performed using SPSS 13.0. Seven dimensions of needs (maintaining health, support from healthcare professionals, knowledge about the disease and treatment, support on funeral, information on hospice care, psychological support for patients and symptoms control for patients) were extracted from the results by factor analysis. The dimension with the highest score was 'knowledge about the disease and treatment' (4.37), and that with the lowest score named 'support on funeral' (2.85). The results showed that the factors including burden of payment for treatment, former caregiving experience of family caregivers and length of caregiving time were associated with their needs. Cancer services need to consider how to tailor resources and interventions to meet these needs of family caregivers of advanced cancer patients.

  4. Refeeding syndrome in a patient with advanced kidney failure due to nephronophthisis.

    PubMed

    El-Reshaid, Kamel

    2013-11-01

    Refeeding syndrome (RS) is a serious and potentially fatal disorder. It is caused by a shift of fluids, sodium, potassium, magnesium and phosphorus as well changes in the metabolism of glucose, protein, fat and vitamins following the refeeding of malnourished patients, whether enterally or parenterally. RS has rarely been reported in patients with advanced kidney disease probably due to the pre-existing hyperphosphatemia, hypermagnesemia and hyperkalemia in these patients. In the following report, we present a patient with nephronophthisis type 1 deletion syndrome in whom her main previous nutrition was limited to simply rehydration to avoid renal replacement therapy. On presentation, she was cachectic and dehydrated with advanced kidney failure. She was treated with medical nephrectomy using non-steroidal anti-inflammatory drugs and then placed on maintenance hemodialysis. Percutaneous endoscopic gastrostomy was used for her initial feeding. Care was exercised during her early refeeding with regard to correction of fluids and essential electrolytes, viz. potassium, phosphorus and magnesium, as well as multivitamins to avoid the cardiovascular and neurological complications of RS. However, the changes in the gut, pancreas and liver as well as her hyperlipidemia were a clear obstacle. Fortunately, the ileus and pancreatitis she developed on refeeding improved dramatically with a decrease of the feeding dose to half; however, the liver abnormalities and hyperlipidemia were severe and slow to recover. These improved after addition of ursodeoxycholic acid and permitted successful increase of the dose of feeding subsequently.

  5. Trends in the Aggressiveness of End-of-Life Care for Advanced Stomach Cancer Patients

    PubMed Central

    Hong, Ji Hyung; Rho, Sang-Young

    2013-01-01

    Purpose It is important to balance the appropriateness of active cancer treatments and end-of-life care to improve the quality of life for terminally ill cancer patients. This study describes the treatment patterns and end-of-life care in terminal gastric cancer patients. Materials and Methods We retrospectively analyzed the records of 137 patients with advanced gastric cancer receiving chemotherapy and dying between June 1, 2006 and May 31, 2011. We recorded interval between last chemotherapy dose and death; frequency of emergency room visits or admission to the intensive care unit in the last month before death; rate of hospice referral and agreement with written do-not-resuscitate orders; and change in laboratory values in the last three months before death. Results During the last six months of life, 130 patients (94.9%) received palliative chemotherapy; 86 (62.7%) during the final two months; 41 (29.9%) during the final month. During the final month, 53 patients (38.7%) visited an emergency room more than once; 21 (15.3%) were admitted to the intensive care unit. Hospice referral occurred in 54% (74 patients) of the patients; 93.4% (128 patients) gave written do-not-resuscitate orders. Platelets, aspartate aminotransferase and creatinine changed significantly two weeks before death; total bilirubin, one month before; and C-reactive protein, between four and two weeks before death. Conclusion Our results demonstrated that a significant proportion of gastric cancer patients received palliative chemotherapy to the end of life and the patients who stopped the chemotherapy at least one month before death had a lower rate of intensive care unit admission and longer overall survival than those who sustained aggressive chemotherapy until the last months of their lives. PMID:24453999

  6. Clinical profile of patients with advanced age and inflammatoric dilated cardiomyopathy on endomyocardial biopsy

    PubMed Central

    Ohlow, Marc-Alexander; Chen, Ting-Hui; Schmidt, Andreas; Saenger, Joerg; Lauer, Bernward

    2015-01-01

    Background Endomyocardial biopsy (EMB) is an important tool when patients with inflammatoric cardiomyopathy (DCMi) are evaluated. We aimed to assess the clinical profile of elderly patients with DCMi on EMB. Methods Retrospective study of all consecutive patients hospitalized from January 2007 to December 2011 with clinical suspicion of DCMi undergoing EMB. Patients with evidence of DCMi on EMB (Group 1 ≥ 70 years, n = 85; Group 3 < 70 years; n = 418) were compared to patients of the same age group without evidence of DCMi on EMB (Group 2 ≥ 70 years, n = 45; Group 4 < 70 years; n = 147). Results Among 24,275 patients treated at our institution during the study period, 695 had clinical suspicion of DCMi and underwent EMB; 503 (2.1%) patients had DCMi on EMB. There were more male patients in Group 1, mean age was 74 ± 2.8 years, mean ejection fraction was 38% ± 14%. On presentation, signs of hemodynamic compromise (NYHA functional class III/IV, low cardiac output/index, and low cardiac power index) were more frequent in Group 1. EMB revealed viral genome in 78% of the patients, parvovirus B19 (PVB) was frequently encountered in both age groups (Group 1: 69.4% vs. Group 2: 59.6%); detection of more than one viral genome was more frequent in Group 1 (21.2% vs. 11.2%; P = 0.02) whereas the extent of immune response was significantly lower in individuals with advanced age. Conclusions In patients ≥ 70 years with DCMi on EMB signs of hemodynamic compromise, detection of multiple viral genomes together with an overall lower extent of immune response were more frequently observed. PMID:26788036

  7. Outcome of unilateral pallidotomy in advanced Parkinson's disease: cohort study of 32 patients

    PubMed Central

    de Bie, R M A; Schuurman, P; Bosch, D; de Haan, R J; Schmand, B; Speelman, J

    2001-01-01

    OBJECTIVES—In a randomised trial to study the efficacy of unilateral pallidotomy in patients with advanced Parkinson's disease, patients having pallidotomy within 1 month after randomisation were compared with patients having pallidotomy 6 months after the primary outcome assessment. Of the 37 patients enrolled 32 had a unilateral pallidotomy. The follow up study of these patients is presented to report (1) clinical outcome; (2) adverse effects; (3) cognitive and behavioural effects; (4) relation between lesion location and outcome; and (5) preoperative patient characteristics predictive for good outcome.
METHODS—Outcome measures were the motor section of the unified Parkinson's disease rating scale (UPDRS), levodopa induced dyskinesias, disability, quality of life, and a comprehensive neuropsychological assessment. Multivariate logistic regression was used to identify preoperative patient characteristics independently associated with good outcome.
RESULTS—Off phase assessment showed a reduction in parkinsonism from 49 to 36.5 points on the UPDRS 6 months after surgery. Improvements were also demonstrated for activities of daily living and quality of life. In the on phase dyskinesias were reduced. All effects lasted up to 12 months after surgery. Three patients had major permanent adverse effects. Besides worsening of verbal fluency after left sided surgery, systematic cognitive deterioration was not detected. Patients taking less than 1000 levodopa equivalent units (LEU)/day were more likely to improve.
CONCLUSIONS—The positive effects of unilateral pallidotomy are stable up to 1 year after surgery. Patients taking less than 1000 LEU per day were most likely to improve.

 PMID:11511714

  8. [The quality of life after chemotherapy in advanced non-small cell lung cancer patients].

    PubMed

    Słowik-Gabryelska, A; Szczepanik, A; Kalicka, A

    1999-01-01

    The intensity of complains, short survival and great number of patients makes many oncologists to apply chemotherapy in advanced non-small cell lung cancer/NSCLC/. The achieved median duration of life after chemotherapy was 6 to 12 month. From the other hand non small cell lung cancer chemotherapy is a big burden even to healthy persons. It can worsen the quality of life. That was the reason we evaluated the quality of life after chemotherapy in advanced non small cell lung cancer patients. Taking into account, that the evaluation of quality of life, used in most diseases is useless in advanced NSCLC patients, for appreciation the quality of life in these cases the lung cancer symptoms scale/LCSS/was adopted. In 110 non small cell lung cancer patients in stage IIIB and IV, who received combined chemotherapy by Le Chevalier/Vindesine, Cisplatin, Cyclophosphamide, Lomustin/or by Rosell/Mitomycin, Cyclophosphamide, Cisplatin/the quality of life was evaluated. In 20-persons control group all patients received the symptomatic treatment. In observed group of 110 patients, tumor regressions after 4 courses of chemotherapy allowed to resect cancer in 14 cases, to apply radiotherapy in 42 and to continue chemiotherapy in 23 persons. In every person from above mentioned group the quality of life was evaluated on the basis of intensity of cancer symptoms, accordingly to LCSS. The intensity of cancer symptoms was compared before and after treatment. There were compared; the innensity of complains, weakness, appetite, malnutrition, and hematological, neurological, performans state as well as respiratory sufficiency, infections, cardiac disorders and pain. Apart it, the side effects of applied therapy were assessed in 5 degree scale. The level of hemoglobin, the number of leucocytes, thrombocytes, bilirubine and transaminases in peripheral blood, hematurie, proteinurie, bleedings, appetite, nausea, vomitings, diarrhea, mucosal lesions, infections, skin lesions, cardiac lesions

  9. A proposed predictive model for advanced fibrosis in patients with chronic hepatitis B and its validation.

    PubMed

    Nishikawa, Hiroki; Hasegawa, Kunihiro; Ishii, Akio; Takata, Ryo; Enomoto, Hirayuki; Yoh, Kazunori; Kishino, Kyohei; Shimono, Yoshihiro; Iwata, Yoshinori; Nakano, Chikage; Nishimura, Takashi; Aizawa, Nobuhiro; Sakai, Yoshiyuki; Ikeda, Naoto; Takashima, Tomoyuki; Iijima, Hiroko; Nishiguchi, Shuhei

    2016-08-01

    We created a predictive model using serum-based biomarkers for advanced fibrosis (F3 or more) in patients with chronic hepatitis B (CHB) and to confirm the accuracy in an independent cohort.A total of 249 CHB patients were analyzed. To achieve our study aim, a training group (n = 125) and a validation group (n = 124) were formed. In the training group, parameters related to the presence of advanced fibrosis in univariate and multivariate analyses were examined, and a formula for advanced fibrosis was created. Next, we verified the applicability of the predictive model in the validation group.Multivariate analysis identified that gamma-glutamyl transpeptidase (GGT, P = 0.0343) and platelet count (P = 0.0034) were significant predictors of the presence of advanced fibrosis, while Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA-M2BP, P = 0.0741) and hyaluronic acid (P = 0.0916) tended to be significant factors. Using these 4 parameters, we created the following formula: GMPH score = -0.755 - (0.015 × GGT) - (0.268 × WFA-M2BP) + (0.167 × platelet count) + (0.003 × hyaluronic acid). In 8 analyzed variables (WFA-M2BP, aspartate aminotransferase-to-platelet ratio index, FIB-4 index, prothrombin time, platelet count, hyaluronic acid, Forns index, and GMPH score), GMPH score had the highest area under the receiver operating characteristic (AUROC) curve for advanced fibrosis with a value of 0.8064 in the training group and in the validation group, GMPH score also had the highest AUROC (0.7782). In all subgroup analyses of the hepatitis B virus (HBV) status (HB surface antigen quantification, HBV-DNA quantification, and HBe antigen seropositivity), GMPH score in F3 or F4 was significantly lower than that in F0 to F2. In the above mentioned 8 variables, differences between the liver fibrosis stages (F0 to F1 vs F2, F2 vs F3, F3 vs F4, F0 to F1 vs F3, F0 to F1 vs F4, and F2 vs F4) for the entire

  10. A proposed predictive model for advanced fibrosis in patients with chronic hepatitis B and its validation

    PubMed Central

    Nishikawa, Hiroki; Hasegawa, Kunihiro; Ishii, Akio; Takata, Ryo; Enomoto, Hirayuki; Yoh, Kazunori; Kishino, Kyohei; Shimono, Yoshihiro; Iwata, Yoshinori; Nakano, Chikage; Nishimura, Takashi; Aizawa, Nobuhiro; Sakai, Yoshiyuki; Ikeda, Naoto; Takashima, Tomoyuki; Iijima, Hiroko; Nishiguchi, Shuhei

    2016-01-01

    Abstract We created a predictive model using serum-based biomarkers for advanced fibrosis (F3 or more) in patients with chronic hepatitis B (CHB) and to confirm the accuracy in an independent cohort. A total of 249 CHB patients were analyzed. To achieve our study aim, a training group (n = 125) and a validation group (n = 124) were formed. In the training group, parameters related to the presence of advanced fibrosis in univariate and multivariate analyses were examined, and a formula for advanced fibrosis was created. Next, we verified the applicability of the predictive model in the validation group. Multivariate analysis identified that gamma-glutamyl transpeptidase (GGT, P = 0.0343) and platelet count (P = 0.0034) were significant predictors of the presence of advanced fibrosis, while Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP, P = 0.0741) and hyaluronic acid (P = 0.0916) tended to be significant factors. Using these 4 parameters, we created the following formula: GMPH score = −0.755 − (0.015 × GGT) − (0.268 × WFA+-M2BP) + (0.167 × platelet count) + (0.003 × hyaluronic acid). In 8 analyzed variables (WFA+-M2BP, aspartate aminotransferase-to-platelet ratio index, FIB-4 index, prothrombin time, platelet count, hyaluronic acid, Forns index, and GMPH score), GMPH score had the highest area under the receiver operating characteristic (AUROC) curve for advanced fibrosis with a value of 0.8064 in the training group and in the validation group, GMPH score also had the highest AUROC (0.7782). In all subgroup analyses of the hepatitis B virus (HBV) status (HB surface antigen quantification, HBV-DNA quantification, and HBe antigen seropositivity), GMPH score in F3 or F4 was significantly lower than that in F0 to F2. In the above mentioned 8 variables, differences between the liver fibrosis stages (F0 to F1 vs F2, F2 vs F3, F3 vs F4, F0 to F1 vs F3, F0 to F1 vs F4, and F2 vs

  11. Quality of life in patients with venous stasis ulcers and others with advanced venous insufficiency.

    PubMed

    Tracz, Edyta; Zamojska, Ewa; Modrzejewski, Andrzej; Zaborski, Daniel; Grzesiak, Wilhelm

    2015-01-01

    The quality of life (QoL) in patients with advanced venous insufficiency (including venous stasis ulcers, skin discoloration, stasis eczema, and lipodermatosclerosis) assessed using the Clinical Etiological Anatomical Pathophysiological (CEAP) and Venous Clinical Severity Score (VCSS) classifications is presented. Also, disease features such as: intensity of pain, edema and inflammatory response that exerted the most profound effect on different domains of QoL are reported. The global QoL in patients with lower leg venous ulcerations was relatively similar to that observed in other patients with chronic venous insufficiency. The presence of venous ulcerations was associated with lower QoL in a Physical domain. Significant correlations were found between pain intensity and the values of Physical, Physiological, Level of Independence and Environmental domains, between edema intensity and Social domain as well as between the intensity of inflammatory response and Physical and Spiritual domains.

  12. Physical activity in patients with advanced-stage cancer: a systematic review of the literature.

    PubMed

    Albrecht, Tara A; Taylor, Ann Gill

    2012-06-01

    The importance of physical activity for chronic disease prevention and management has become generally well accepted. The number of research interventions and publications examining the benefits of physical activity for patients with cancer has been rising steadily. However, much of that research has focused on the impact of physical activity either prior to or early in the cancer diagnosis, treatment, and survivorship process. Research focusing on the effects of physical activity, specifically for patients with advanced-stage cancer and poorer prognostic outcomes, has been addressed only recently. The purpose of this article is to examine the state of the science for physical activity in the advanced-stage disease subset of the cancer population. Exercise in a variety of intensities and forms, including yoga, walking, biking, and swimming, has many health benefits for people, including those diagnosed with cancer. Research has shown that, for people with cancer (including advanced-stage cancer), exercise can decrease anxiety, stress, and depression while improving levels of pain, fatigue, shortness of breath, constipation, and insomnia. People diagnosed with cancer should discuss with their oncologist safe, easy ways they can incorporate exercise into their daily lives. PMID:22641322

  13. Clinical Neuropathology mini-review 6-2015: PD-L1: emerging biomarker in glioblastoma?

    PubMed Central

    Preusser, Matthias; Berghoff, Anna S.; Wick, Wolfgang; Weller, Michael

    2015-01-01

    Programmed death 1 (PD-1, CD279) and programmed death ligand 1 (PD-L1, CD274) are involved in generating tumor-associated immunosuppression by suppression of T-cell proliferation and interleukin 2 (IL-2) production and immune checkpoint inhibitors targeting these molecules are showing compelling activity against a variety of human cancers. PD-L1 expression has shown a positive association with response to PD-1 inhibition in non-central nervous system (CNS) tumors, e.g., melanoma or non-small cell lung cancer, and is discussed as a potential predictive biomarker for patient selection in these tumor types. This review summarizes current knowledge and potential clinical implications of PD-L1 expression in glioblastoma. At present, the following conclusions are drawn: (a) functional data support a role for PD-1/PD-L1 in tumor-associated immunosuppression in glioblastoma; (b) the incidence of PD-L1-expressing glioblastomas seems to be relatively high in comparison to other tumor types, however, the reported rates of glioblastomas with PD-L1 protein expression vary and range from 61 to 88%; (c) there is considerable variability in the methodology of PD-L1 assessment in glioblastoma across studies with heterogeneity in utilized antibodies, tissue sampling strategies, immunohistochemical staining protocols, cut-off definitions, and evaluated staining patterns; (d) there are conflicting data on the prognostic role and so far no data on the predictive role of PD-L1 gene and protein expression in glioblastoma. In summary, the ongoing clinical studies evaluating the activity of PD-1/PD-L1 inhibitors in glioblastoma need to be complemented with well designed and stringently executed studies to understand the influence of PD-1/PD-L1 expression on therapy response or failure and to develop robust means of PD-L1 assessment for meaningful biomarker development. PMID:26501438

  14. Quality of life and palliative care needs of elderly patients with advanced heart failure

    PubMed Central

    Chan, Helen YL; Yu, Doris SF; Leung, Doris YP; Chan, Aileen WK; Hui, Elsie

    2016-01-01

    Objective To examine the quality of life and palliative care needs of elderly patients with advanced heart failure (HF). Methods This was a correlation descriptive study conducted at a 650-bed sub-acute hospital. Patients who were aged 65 or over, diagnosed with HF of New York Heart Association Class III or IV symptoms, and mentally sound were eligible to the study. The Edmonton Symptom Assessment Scale, the overall quality of life single item scale, and the McQill Quality of Life Questionnaire (MQoL), were used for measurement. Multiple regression analysis was performed to determine factors for predicting quality of life. Results A convenience sample of 112 patients was recruited. Their age was 81.5 ± 8.5 years. The three most distressing symptoms reported by the patients were tiredness (5.96 ± 2.78), drowsiness (5.47 ± 2.93), and shortness of breath (5.34 ± 2.96). Their mean overall quality of life single item scale score was 4.72 ± 2.06 out of 10. The mean MQoL physical subscale score was the lowest (4.20 ± 1.767), whereas their mean psychological subscale was the highest (7.14 ± 2.39). However, in a multivariate analysis model, quality of life was significantly associated with existential wellbeing, physical wellbeing, psychological wellbeing and educational level. Conclusions The findings highlight that spiritual concerns are significant palliative care needs among elderly patients with advanced HF, in addition to symptom management. This is in line with the argument that palliative care that places great emphasis on holistic care should be integrated to the care of this group of patients. PMID:27594869

  15. [Immune Checkpoint Inhibitors for Advanced Melanoma - Evidences and Future Perspectives].

    PubMed

    Nakamura, Yasuhiro; Teramoto, Yukiko; Asami, Yuri; Matsuya, Taisuke; Yamamoto, Akifumi

    2016-09-01

    Recently developed immune checkpoint inhibitors, such as anti-PD-1 antibodies, have shown a clear improvement in clinical efficacy compared with conventional cytotoxic chemotherapy in the treatment of patients with advanced melanoma. Treatment with anti-PD-1 antibodies has resulted in improved objective response rates, longer durations of response, and longer overall survival rates. Although the incidence rate of adverse events associated with anti-PD-1 antibodies is lower than that associated with cytotoxic agents, characteristic severe adverse events such as pneumonia, endocrinopathy, and colitis can occur. A recent clinical trial that evaluated the utility of an anti-PD-1 antibody in combination with an anti-CTLA-4 antibody reported that the treatment enhanced clinical efficacy in terms of response rate and progression-free survival. However, the incidence of adverse events and treatment discontinuation also increased. For optimal selection of immune checkpoint inhibitors for treating patients with advanced melanoma, biomarkers capable of predicting clinical efficacy, prognosis, and adverse events in each patient need to be identified. In addition, novel combination therapies, including immune checkpoint inhibitors and MAP kinase pathway-targeting agents, should result in more favorable clinical responses and prolonged overall survival rates. PMID:27628544

  16. Hypermetabolism and symptom burden in advanced cancer patients evaluated in a cachexia clinic

    PubMed Central

    Dev, Rony; Hui, David; Chisholm, Gary; Delgado-Guay, Marvin; Dalal, Shalini; Del Fabbro, Egidio; Bruera, Eduardo

    2015-01-01

    Background Elevated resting energy expenditure (REE) may contribute to weight loss and symptom burden in cancer patients. Aims The aim of this study was to compare the velocity of weight loss, symptom burden (fatigue, insomnia, anxiety, and anorexia—combined score as measured by the Edmonton Symptom Assessment Score), high-sensitivity C-reactive protein, and survival among cancer patients referred to a cachexia clinic with hypermetabolism, elevated REE > 110% of predicted, with normal REE. Methods A retrospective analysis of 60 advanced cancer patients evaluated in a cachexia clinic for either >5% weight loss or anorexia who underwent indirect calorimetry to measure REE. Patients were dichotomized to either elevated or normal REE. Descriptive statistics were generated, and a two-sample Student's t-tests were used to compare the outcomes between the groups. Kaplan–Meier and Cox regression methodology were used to examine the survival times between groups. Results Thirty-seven patients (62%) were men, 41 (68%) were White, 59 (98%) solid tumours, predominantly 23 gastrointestinal cancers (38%), with a median age of 60 (95% confidence interval 57.0–62.9). Thirty-five patients (58%) were hypermetabolic. Non-Caucasian patients were more likely to have high REE [odds ratio = 6.17 (1.56, 24.8), P = 0.01]. No statistical difference regarding age, cancer type, gender, active treatment with chemotherapy, and/or radiation between hypermetabolic and normal REE was noted. The velocity of weight loss over a 3 month period (−8.5 kg vs. −7.2 kg, P = 0.68), C-reactive protein (37.3 vs. 55.6 mg/L, P = 0.70), symptom burden (4.2 vs. 4.5, P = 0.54), and survival (288 vs. 276 days, P = 0.68) was not significantly different between high vs. normal REE, respectively. Conclusion Hypermetabolism is common in cancer patients with weight loss and noted to be more frequent in non-Caucasian patients. No association among velocity of weight loss

  17. [Respecting patient's end of life wishes: feasibility study of an information on surrogate and advance directives].

    PubMed

    Vinant, Pascale; Rousseau, Isabelle; Huillard, Olivier; Goldwasser, François; Guillard, Marie-Yvonne; Colombet, Isabelle

    2015-03-01

    This prospective interventional study aims to show the feasibility and impact of information procedure on surrogate and advance directives (AD), for patients with incurable lung or gastrointestinal cancer. The intervention consisted of two semi-structured interviews. The first included: collection of preferences for prognostic information and involvement in decision-making, initial assessment of knowledge, information and surrogate and DA. The second assessed the impact of the first interview on knowledge, surrogate designation and DA writing, the assessment procedure by the patient and assessment of anxiety generated. Among 77 eligible patients, 23 (30 %) were included, 6/29 (21 %) refused to participate, 20/23 (87 %) completed both interviews. Patients not included had a higher 4-month death rate than included ones (39 % vs. 4 %, P=0.002). Patients included had high expectations of information and appreciated it be delivered early, by someone not involved in their care. The study shows the feasibility of the procedure and its impact on the use of surrogate and DA by patients, however, revealing the complexity of approaching end-of-life wills and the importance of a process of anticipated discussion.

  18. [Respecting patient's end of life wishes: feasibility study of an information on surrogate and advance directives].

    PubMed

    Vinant, Pascale; Rousseau, Isabelle; Huillard, Olivier; Goldwasser, François; Guillard, Marie-Yvonne; Colombet, Isabelle

    2015-03-01

    This prospective interventional study aims to show the feasibility and impact of information procedure on surrogate and advance directives (AD), for patients with incurable lung or gastrointestinal cancer. The intervention consisted of two semi-structured interviews. The first included: collection of preferences for prognostic information and involvement in decision-making, initial assessment of knowledge, information and surrogate and DA. The second assessed the impact of the first interview on knowledge, surrogate designation and DA writing, the assessment procedure by the patient and assessment of anxiety generated. Among 77 eligible patients, 23 (30 %) were included, 6/29 (21 %) refused to participate, 20/23 (87 %) completed both interviews. Patients not included had a higher 4-month death rate than included ones (39 % vs. 4 %, P=0.002). Patients included had high expectations of information and appreciated it be delivered early, by someone not involved in their care. The study shows the feasibility of the procedure and its impact on the use of surrogate and DA by patients, however, revealing the complexity of approaching end-of-life wills and the importance of a process of anticipated discussion. PMID:25732047

  19. [Physicians' views and perspectives on advanced directives in patients with incipient dementia].

    PubMed

    Mattiussi, Mercedes; Dawidowski, Adriana; Restibo, Jimena; Pollán, Javier; Pezzano, Laura; Cámera, Luis

    2012-01-01

    Dementia is a progressive disease in which patients lose their ability to decide and communicate. Advance directives (AD) allow patients to express their preferences on end of life care in the early stages of the disease. Primary care practitioners (PCP) are in the best position to promote AD. The aim of this study was to elicit PCPs views about the discussion of AD with early stage dementia patients. A qualitative approach was taken, focus groups and individual interviews to elderly patients' PCPs from the Hospital italiano de buenos aires were conducted. A purposive sampling was performed, conforming homogeneous groups according to age and seniority. The discussion was stimulated by a vignette. We performed thematic content analysis in an interdisciplinary team. Twelve PCPs = 30 year of age, 32 middle-aged and 8 over 45 years participated of the study. The youngest group favored the discussion of AD while those over 45 regarded the family as the decision maker, and thus, the discussion as useless. Besides, they expressed that our society is not mature enough to discuss AD. Difficulties in AD implementation, in predicting the evolution of a patient's disease, the span of time between the discussion and AD implementation, lack of legislation and specific institutional policies were other factors that conditioned the discussion. Younger PCPs expressed concern on the lack of communication skills and difficulties to broach this subject with patients. PCPs perspectives on AD vary, their age should be taken into account when designing strategies to their implementation.

  20. Fatigue is the Most Important Symptom for Advanced Cancer Patients Who Have Had Chemotherapy

    PubMed Central

    Butt, Zeeshan; Rosenbloom, Sarah K.; Abernethy, Amy P.; Beaumont, Jennifer L.; Paul, Diane; Hampton, Debra; Jacobsen, Paul B.; Syrjala, Karen L.; Von Roenn, Jamie H.; Cella, David

    2016-01-01

    Cancer fatigue has been defined and described as an important problem. However, few studies have assessed the relative importance of fatigue compared with other patient symptoms and concerns. To explore this issue, the authors surveyed 534 patients and 91 physician experts from 5 NCCN member institutions and community support agencies. Specifically, they asked patients with advanced bladder, brain, breast, colorectal, head and neck, hepatobiliary/pancreatic, kidney, lung, ovarian, or prostate cancer or lymphoma about their “most important symptoms or concerns to monitor.” Across the entire sample, and individually for patients with 9 cancer types, fatigue emerged as the top-ranked symptom. Fatigue was also ranked most important among patients with 10 of 11 cancer types when asked to rank lists of common concerns. Patient fatigue ratings were most strongly associated with malaise (r = 0.50) and difficulties with activities of daily living, pain, and quality of life. Expert ratings of how much fatigue is attributable to disease versus treatment mostly suggested that both play an important role, with disease-related factors predominant in hepatobiliary and lung cancer, and treatment-related factors playing a stronger role in head and neck cancer. PMID:18492460

  1. Predicting compliance for mandible advancement splint therapy in 96 obstructive sleep apnea patients.

    PubMed

    Ingman, Tuula; Arte, Sirpa; Bachour, Adel; Bäck, Leif; Mäkitie, Antti

    2013-12-01

    The treatment of choice in obstructive sleep apnea (OSA) is continuous positive airway pressure (CPAP). Mandible advancement splint (MAS) offers an option for patients with mild or moderate OSA, who refuse or are unable to tolerate CPAP. The aim of the study was to find predictive factors in OSA for MAS therapy. The study group comprised 96 consecutive OSA patients who were sent for MAS therapy during 2008. Data were collected on the patients' general and dental condition, diagnosis, and treatment for OSA. Panoramic and cephalometric radiographs were analysed. The treatment compliance rate and problems with the use of the MAS were recorded. This rate was 57% and the significant affecting factors were protrusion of the mandible with MAS during the adaptation to the appliance as well as shorter maxillary and mandible lengths. The compliance of the MAS therapy was best in patients with short maxilla and mandible, which should be taken into consideration when planning MAS therapy for OSA patients. Finally, a sleep study should be part of the follow-up in this patient population. PMID:23159421

  2. The best timing for administering systemic chemotherapy in patients with locally advanced rectal cancer

    PubMed Central

    Shimodaira, Yusuke; Harada, Kazuto; Lin, Quan

    2016-01-01

    Over the past several decades, outcomes for patients with rectal cancer have improved considerably. However, several questions have emerged as survival times have lengthened and quality of life has improved for these patients. Currently patients with locally advanced rectal cancer (LARC) are often recommended multimodality therapy with fluoropyrimidine-based chemotherapy (CT) and radiation followed by total mesorectal excision (TME), with consideration given to FOLFOX before chemoradiotherapy (CRT). Recently, Garcia-Aguilar and colleagues reported in Lancet Oncology that the addition of mFOLFOX6 administered between CRT and surgery affected the number of patients achieving pathologic complete response (pathCR), which is of great interest from the standpoint of pursuit of optimal timing of systemic CT delivery. This was a multicenter phase II study consisting of 4 sequential treatment groups of patients with LARC, and they reported that patients given higher number CT cycles between CRT and surgery achieved higher rates of pathCR than those given standard treatment. There was no association between response improvement and tumor progression, increased technical difficulty, or surgical complications. Ongoing phase III clinical trial further assessing this strategy might result in a paradigm shift. PMID:26889491

  3. Concurrent cisplatin, 5-FU, paclitaxel, and radiation therapy in patients with locally advanced esophageal cancer

    SciTech Connect

    Roof, Kevin S. . E-mail: kroof@sero.net; Coen, John; Lynch, Thomas J.; Wright, Cameron; Fidias, Panos; Willett, Christopher G.; Choi, Noah C.

    2006-07-15

    Purpose: Phase I-II data regarding neoadjuvant cisplatin, 5-fluorouracil (5-FU), paclitaxel, and radiation (PFT-R) from our institution demonstrated encouraging pathologic complete response (pCR) rates. This article updates our experience with PFT-R, and compares these results to our experience with cisplatin, 5-FU, and radiation therapy (PF-R) in locally advanced esophageal cancer. Patients and Methods: We searched the Massachusetts General Hospital cancer registry for esophageal cancer patients treated with radiation therapy and chemotherapy between 1994-2002. Records of patients treated with curative, neoadjuvant therapy were examined for chemotherapeutic regimen. Outcomes of patients treated with PF-R or PFT-R were assessed for response to therapy, toxicity, and survival. Results: A total of 177 patients were treated with neoadjuvant therapy with curative intent; 164 (93%) received PF-R (n = 81) or PFT-R (n = 83). Median overall survival was 24 months. After a median follow-up of 54 months for surviving patients, 3-year overall survival was 40% with no significant difference between PF-R (39%) and PFT-R (42%). Conclusions: Our findings failed to demonstrate an improvement in pCR or survival with PFT-R vs. PF-R. These results do not support this regimen of concurrent neoadjuvant PFT-R in esophageal cancer, and suggest that further investigations into alternative regimens and novel agents are warranted.

  4. Telomere length is a prognostic biomarker in elderly advanced ovarian cancer patients: a multicenter GINECO study

    PubMed Central

    Falandry, Claire; Horard, Béatrice; Bruyas, Amandine; Legouffe, Eric; Cretin, Jacques; Meunier, Jérôme; Alexandre, Jérôme; Delecroix, Valérie; Fabbro, Michel; Certain, Marie-Noëlle; Maraval-Gaget, Raymonde; Pujade-Lauraine, Eric; Gilson, Eric; Freyer, Gilles

    2015-01-01

    Purpose Age induces a progressive decline in functional reserve and impacts cancer treatments. Telomere attrition leads to tissue senescence. We tested the hypothesis that telomere length (TL) could predict patient vulnerability and outcome with cancer treatment. Patients and methods An ancillary study in the Elderly Women GINECO Trial 3 was performed to evaluate the impact of geriatric covariates on survival in elderly advanced ovarian cancer patients receiving six cycles of carboplatin. TL was estimated from peripheral blood at inclusion using standard procedures. Results TL (in base pairs) was estimated for 109/111 patients (median 6.1 kb; range [4.5-8.3 kb]). With a cut-off of 5.77 kb, TL discriminated two patient groups, long telomere (LT) and short telomeres (ST), with significantly different treatment completion rates of 0.80 (95%CI [0.71-0.89]) and 0.59 (95%CI [0.41-0.76]), respectively (odds ratio [OR]=2.8, p=0.02). ST patients were at higher risk of serious adverse events (SAE, OR=2.7; p=0.02) and had more unplanned hospital admissions (OR=2.1; p=0.08). After adjustment on FIGO stage, TL shorter than 6 kb was a risk factor of premature death (HR=1.57; p=0.06). Conclusion This exploratory study identifies TL as predictive factor of decreased treatment completion, SAE risk, unplanned hospital admissions and OS after adjustment on FIGO stage. PMID:26638179

  5. Predicting compliance for mandible advancement splint therapy in 96 obstructive sleep apnea patients.

    PubMed

    Ingman, Tuula; Arte, Sirpa; Bachour, Adel; Bäck, Leif; Mäkitie, Antti

    2013-12-01

    The treatment of choice in obstructive sleep apnea (OSA) is continuous positive airway pressure (CPAP). Mandible advancement splint (MAS) offers an option for patients with mild or moderate OSA, who refuse or are unable to tolerate CPAP. The aim of the study was to find predictive factors in OSA for MAS therapy. The study group comprised 96 consecutive OSA patients who were sent for MAS therapy during 2008. Data were collected on the patients' general and dental condition, diagnosis, and treatment for OSA. Panoramic and cephalometric radiographs were analysed. The treatment compliance rate and problems with the use of the MAS were recorded. This rate was 57% and the significant affecting factors were protrusion of the mandible with MAS during the adaptation to the appliance as well as shorter maxillary and mandible lengths. The compliance of the MAS therapy was best in patients with short maxilla and mandible, which should be taken into consideration when planning MAS therapy for OSA patients. Finally, a sleep study should be part of the follow-up in this patient population.

  6. Advance Care Planning: A Qualitative Study of Dialysis Patients and Families

    PubMed Central

    Eneanya, Nwamaka D.; Feinberg, Rebecca; Germain, Michael J.; Marr, Lisa; Berzoff, Joan; Cohen, Lewis M.; Unruh, Mark

    2015-01-01

    Background and objectives More than 90,000 patients with ESRD die annually in the United States, yet advance care planning (ACP) is underutilized. Understanding patients’ and families’ diverse needs can strengthen systematic efforts to improve ACP. Design, setting, participants, & measurements In-depth interviews were conducted with a purposive sample of patients and family/friends from dialysis units at two study sites. Applying grounded theory, interviews were audiotaped, professionally transcribed, and analyzed in an iterative process. Emergent themes were identified, discussed, and organized into major themes and subthemes. Results Thirteen patients and nine family/friends participated in interviews. The mean patient age was 63 years (SD 14) and five patients were women. Participants identified as black (n=1), Hispanic (n=4), Native American (n=4), Pacific Islander (n=1), white (n=11), and mixed (n=1). Three major themes with associated subthemes were identified. The first theme, “Prior experiences with ACP,” revealed that these discussions rarely occur, yet most patients desire them. A potential role for the primary care physician was broached. The second theme, “Factors that may affect perspectives on ACP,” included a desire for more of a connection with the nephrologist, positive and negative experiences with the dialysis team, disenfranchisement, life experiences, personality traits, patient-family/friend relationships, and power differentials. The third theme, “Recommendations for discussing ACP,” included thoughts on who should lead discussions, where and when discussions should take place, what should be discussed and how. Conclusions Many participants desired better communication with their nephrologist and/or their dialysis team. A number expressed feelings of disenfranchisement that could negatively impact ACP discussions through diminished trust. Life experiences, personality traits, and relationships with family and friends may

  7. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination.

    PubMed

    Boutros, Celine; Tarhini, Ahmad; Routier, Emilie; Lambotte, Olivier; Ladurie, Francois Leroy; Carbonnel, Franck; Izzeddine, Hassane; Marabelle, Aurelien; Champiat, Stephane; Berdelou, Armandine; Lanoy, Emilie; Texier, Matthieu; Libenciuc, Cristina; Eggermont, Alexander M M; Soria, Jean-Charles; Mateus, Christine; Robert, Caroline

    2016-08-01

    Inhibition of immune checkpoints using anti-programmed cell death-1 (PD-1) or anti cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibodies has revolutionized the management of patients with advanced-stage melanoma and is among the most promising treatment approaches for many other cancers. Use of CTLA-4 and PD-1 inhibitors, either as single agents, or in combination, has been approved by the US FDA for the treatment of metastatic melanoma. Treatment with these novel immunotherapies results in a unique and distinct spectrum of adverse events, which are mostly related to activation of the immune system and are, therefore, an unwanted consequence of their mechanisms of action. Adverse effects of CTLA-4 and/or PD-1 inhibition are most commonly observed in the skin, gastrointestinal tract, liver and endocrine systems and include pruritus, rash, nausea, diarrhoea and thyroid disorders. In this Review, the authors describe the adverse event profile of checkpoint inhibitors targeting CTLA-4 and PD-1, used both as monotherapies and in combination and aim to provide some general guidelines, based upon the mechanisms of action of these therapies and on the management of these immune-related adverse events.

  8. In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma

    PubMed Central

    Philipp-Abbrederis, Kathrin; Herrmann, Ken; Knop, Stefan; Schottelius, Margret; Eiber, Matthias; Lückerath, Katharina; Pietschmann, Elke; Habringer, Stefan; Gerngroß, Carlos; Franke, Katharina; Rudelius, Martina; Schirbel, Andreas; Lapa, Constantin; Schwamborn, Kristina; Steidle, Sabine; Hartmann, Elena; Rosenwald, Andreas; Kropf, Saskia; Beer, Ambros J; Peschel, Christian; Einsele, Hermann; Buck, Andreas K; Schwaiger, Markus; Götze, Katharina; Wester, Hans-Jürgen; Keller, Ulrich

    2015-01-01

    CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination and poor prognosis. We evaluated the novel CXCR4 probe [68Ga]Pentixafor for in vivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [68Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [68Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [18F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34+ flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [68Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases. PMID:25736399

  9. Prognostic significance of CT-emphysema score in patients with advanced squamous cell lung cancer

    PubMed Central

    Kim, Young Saing; Ahn, Hee Kyung; Cho, Eun Kyung; Jeong, Yu Mi; Kim, Jeong Ho

    2016-01-01

    Background Although emphysema is a known independent risk factor of lung cancer, no study has addressed the prognostic impact of computed tomography (CT)-emphysema score in advanced stage lung cancer. Methods For 84 consecutive patients with stage IIIB and IV squamous cell lung cancer that underwent palliative chemotherapy, severity of emphysema was semi-quantitatively scored using baseline chest CT images according to the Goddard scoring system (possible scores range, 0–24). The cutoff of high CT-emphysema score was determined using the maximum chi-squared test and the prognostic significance of the high CT-emphysema score was evaluated using Kaplan-Meier analysis and Cox proportional hazards analysis. Results The median CT-emphysema score was 5 (range, 0–22). Patients with a high CT-emphysema score (≥4) tended to have poorer overall survival (OS) (median: 6.3 vs. 13.7 months) than those with a score of <4 (P=0.071). Multivariable analysis revealed that a higher CT-emphysema score was a significant independent prognostic factor for poor OS [hazard ratio (HR) =2.06; 95% confidence interval (CI), 1.24–3.41; P=0.005), along with no response to first-line therapy (P=0.009) and no second-line therapy (P<0.001). Conclusions CT-emphysema score is significantly associated with poor prognosis in patients with advanced squamous cell lung cancer. PMID:27621848

  10. Advance care planning in nursing homes: pre- and post-Patient Self-Determination Act.

    PubMed Central

    Castle, N G; Mor, V

    1998-01-01

    OBJECTIVES: (1) To identify resident and organizational factors associated with the use of advance care plans pre- and post-implementation of the Patient Self-Determination Act (PSDA), and (2) to identify changes (pre- and post-implementation of the PSDA) in the relationship between these factors and the use of advance care plans. DESIGN: Complex, multistage cluster sampling. SETTING: Ten states were selected for variation in geographic location, Medicaid reimbursement rate, and average staffing patterns. Participants were 4,215 nursing home residents in 268 facilities. PRINCIPAL FINDINGS: Seventeen resident and organizational factors were associated with the use of do-not-resuscitate (DNR) orders in 1990, and 12 resident and organizational factors were associated with their use in 1993. Five factors showed a significant change from 1990 to 1993: activities of daily living (ADL) scores, race, cognitive performance scale (CPS) scores, full-time equivalent (FTE) nurse aides per resident, and bed size. Ten resident and organizational factors were associated with use of do-not-hospitalize (DNH) orders in 1990 and six resident and organizational factors were associated with DNH orders in 1993. Four factors showed a significant change from 1990 to 1993: legal guardian, FTE LPNs per resident, Medicaid census, and forprofit ownership. Five resident and organizational factors were associated with the use of living wills in 1990 and seven resident and organizational factors were associated with the use of living wills in 1993. Four factors showed a significant change from 1990 to 1993: ADL scores, race, length of stay, and for-profit ownership. CONCLUSION: The results indicate that the PSDA may have been successful in increasing the use of advance care plans and in changing the types of residents who use advance care plans. However, they also show that the use of advance care plans is associated with organizational characteristics, indicating that some types of facilities

  11. Perceptions of palliative care among patients with advanced cancer and their caregivers

    PubMed Central

    Zimmermann, Camilla; Swami, Nadia; Krzyzanowska, Monika; Leighl, Natasha; Rydall, Anne; Rodin, Gary; Tannock, Ian; Hannon, Breffni

    2016-01-01

    Background: Early palliative care is increasingly recommended but seldom practised. We sought to examine perceptions of palliative care among patients with advanced cancer and their caregivers. Methods: After conducting a cluster randomized controlled trial of early palliative care versus standard care for patients with advanced cancer, we approached patients and their caregivers to participate in semistructured interviews seeking to assess, qualitatively, their attitudes and perceptions about palliative care. We used the grounded theory method for data collection and analysis. Results: A total of 48 patients (26 intervention, 22 control) and 23 caregivers (14 intervention, 9 control) completed interviews. Participants’ initial perceptions of palliative care in both trial arms were of death, hopelessness, dependency and end-of-life comfort care for inpatients. These perceptions provoked fear and avoidance, and often originated from interactions with health care professionals. During the trial, those in the intervention arm developed a broader concept of palliative care as “ongoing care” that improved their “quality of living” but still felt that the term itself carried a stigma. Participants in the intervention group emphasized the need for palliative care to be reframed and better explained by health care professionals. Participants in the control group generally considered it pointless to rename palliative care, but many in the intervention group stated emphatically that a different name was necessary in the early outpatient setting. Interpretation: There is a strong stigma attached to palliative care, which may persist even after positive experiences with an early palliative care intervention. Education of the public, patients and health care providers is paramount if early integration of palliative care is to be successful. PMID:27091801

  12. Efficacy, Safety, and Biomarkers of Single-Agent Bevacizumab Therapy in Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

    2012-01-01

    Objective. Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which neoangiogenesis contributes to growth and metastasis. We assessed the safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced HCC. Methods. In this phase II trial, eligible patients received bevacizumab, 5 mg/kg or 10 mg/kg every 2 weeks. The disease-control rate at 16 weeks (16W-DCR) was the primary endpoint. Circulating endothelial cells (CECs) and plasma cytokines and angiogenic factors (CAFs) were measured at baseline and throughout treatment. Results. The 16W-DCR was 42% (95% confidence interval, 27%–57%). Six of the 43 patients who received bevacizumab achieved a partial response (objective response rate [ORR], 14%). Grade 3–4 asthenia, hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased (p < .0001); soluble VEGF receptor-2 (p < .0001) and CECs (p = .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (p = .04) and the 16W-DCR (p = .02), respectively. Lower interleukin (IL)-8 levels at baseline (p = .01) and throughout treatment (p ≤ .04) were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p ≤ .04). Conclusion. Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation. PMID:22707516

  13. A Cognitive Behavioral Intervention for Symptom Management in Patients With Advanced Cancer

    PubMed Central

    Sherwood, Paula; Given, Barbara A.; Given, Charles W.; Champion, Victoria L.; Doorenbos, Ardith Z.; Azzouz, Faouzi; Kozachik, Sharon; Wagler-Ziner, Kim; Monahan, Patrick O.

    2006-01-01

    Purpose/Objectives: To evaluate the effectiveness of a cognitive behavioral intervention in decreasing symptom severity in patients with advanced cancer undergoing chemotherapy. Design: Prospective, randomized clinical trial based on cognitive behavioral theory. Setting: Six urban cancer centers in the midwestern United States. Sample: 124 patients 21 years of age or older were recruited and randomized to receive conventional care or conventional care and an intervention. Participants were newly diagnosed with stage III, stage IV, or recurrent cancer (solid tumor or non-Hodgkin lymphoma), undergoing chemotherapy, cognitively intact, and able to read and speak English. Methods: Data were gathered via telephone interviews at baseline and 10 and 20 weeks after randomization. Nurses with experience in oncology delivered a five-contact, eight-week intervention aimed at teaching patients problem-solving techniques to affect symptom severity. Main Research Variables: Gender, site of cancer, age, symptom severity and depressive symptoms at baseline, group (i.e., experimental versus control), and total symptom severity. Findings: Patients in the experimental group and those with lower symptom severity at baseline had significantly lower symptom severity at 10 and 20 weeks; the experimental difference at 20 weeks occurred primarily in those 60 years of age and younger. Depressive symptoms at baseline predicted symptom severity at 20 weeks; however, age, gender, and site of cancer did not affect symptom severity at either time point. Conclusions: Implications for Nursing: Problem-solving strategies should be included in educational programs for patients with advanced cancer, particularly those 60 years of age and younger. PMID:16270114

  14. Efficacy and Factors Affecting Outcome of Gemcitabine Concurrent Chemoradiotherapy in Patients With Locally Advanced Pancreatic Cancer

    SciTech Connect

    Huang, P.-I.; Chao, Yee; Li, C.-P.; Lee, R.-C.; Chi, K.-H.; Shiau, C.-Y.; Wang, L.-W.; Yen, S.-H.

    2009-01-01

    Purpose: To evaluate the efficacy and prognostic factors of gemcitabine (GEM) concurrent chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer. Methods and Materials: Between January 2002 and December 2005, 55 patients with locally advanced pancreatic cancer treated with GEM (400 mg/m{sup 2}/wk) concurrently with radiotherapy (median dose, 50.4 Gy; range, 26-61.2) at Taipei Veterans General Hospital were enrolled. GEM (1,000 mg/m{sup 2}) was continued after CCRT as maintenance therapy once weekly for 3 weeks and repeated every 4 weeks. The response, survival, toxicity, and prognostic factors were evaluated. Results: With a median follow-up of 10.8 months, the 1- and 2-year survival rate was 52% and 19%, respectively. The median overall survival (OS) and median time to progression (TTP) was 12.4 and 5.9 months, respectively. The response rate was 42% (2 complete responses and 21 partial responses). The major Grade 3-4 toxicities were neutropenia (22%) and anorexia (19%). The median OS and TTP was 15.8 and 9.5 months in the GEM CCRT responders compared with 7.5 and 3.5 months in the nonresponders, respectively (both p < 0.001). The responders had a better Karnofsky performance status (KPS) (86 {+-} 2 vs. 77 {+-} 2, p = 0.002) and had received a greater GEM dose intensity (347 {+-} 13 mg/m{sup 2}/wk vs. 296 {+-} 15 mg/m{sup 2}/wk, p = 0.02) than the nonresponders. KPS and serum carbohydrate antigen 19-9 were the most significant prognostic factors of OS and TTP. Conclusion: The results of our study have shown that GEM CCRT is effective and tolerable for patients with locally advanced pancreatic cancer. The KPS and GEM dose correlated with response. Also, the KPS and CA 19-9 level were the most important factors affecting OS and TTP.

  15. Multi-purpose utility of circulating plasma DNA testing in patients with advanced cancers.

    PubMed

    Perkins, Geraldine; Yap, Timothy A; Pope, Lorna; Cassidy, Amy M; Dukes, Juliet P; Riisnaes, Ruth; Massard, Christophe; Cassier, Philippe A; Miranda, Susana; Clark, Jeremy; Denholm, Katie A; Thway, Khin; Gonzalez De Castro, David; Attard, Gerhardt; Molife, L Rhoda; Kaye, Stan B; Banerji, Udai; de Bono, Johann S

    2012-01-01

    Tumor genomic instability and selective treatment pressures result in clonal disease evolution; molecular stratification for molecularly targeted drug administration requires repeated access to tumor DNA. We hypothesized that circulating plasma DNA (cpDNA) in advanced cancer patients is largely derived from tumor, has prognostic utility, and can be utilized for multiplex tumor mutation sequencing when repeat biopsy is not feasible. We utilized the Sequenom MassArray System and OncoCarta panel for somatic mutation profiling. Matched samples, acquired from the same patient but at different time points were evaluated; these comprised formalin-fixed paraffin-embedded (FFPE) archival tumor tissue (primary and/or metastatic) and cpDNA. The feasibility, sensitivity, and specificity of this high-throughput, multiplex mutation detection approach was tested utilizing specimens acquired from 105 patients with solid tumors referred for participation in Phase I trials of molecularly targeted drugs. The median cpDNA concentration was 17 ng/ml (range: 0.5-1600); this was 3-fold higher than in healthy volunteers. Moreover, higher cpDNA concentrations associated with worse overall survival; there was an overall survival (OS) hazard ratio of 2.4 (95% CI 1.4, 4.2) for each 10-fold increase in cpDNA concentration and in multivariate analyses, cpDNA concentration, albumin, and performance status remained independent predictors of OS. These data suggest that plasma DNA in these cancer patients is largely derived from tumor. We also observed high detection concordance for critical 'hot-spot' mutations (KRAS, BRAF, PIK3CA) in matched cpDNA and archival tumor tissue, and important differences between archival tumor and cpDNA. This multiplex sequencing assay can be utilized to detect somatic mutations from plasma in advanced cancer patients, when safe repeat tumor biopsy is not feasible and genomic analysis of archival tumor is deemed insufficient. Overall, circulating nucleic acid

  16. Uterine preservation for advanced pelvic organ prolapse repair: Anatomical results and patient satisfaction

    PubMed Central

    Fink, Keshet; Shachar, Inbar Ben; Braun, Naama Marcus

    2016-01-01

    ABSTRACT Objective: The aims of the current study were to evaluate outcomes and patient satisfaction in cases of uterine prolapse treated with vaginal mesh, while preserving the uterus. Materials and Methods: This is a retrospective cohort study that included all patients operated for prolapse repair with trocar-less vaginal mesh while preserving the uterus between October 2010 and March 2013. Data included: patients pre-and post-operative symptoms, POP-Q and operative complications. Success was defined as prolapse < than stage 2. A telephone survey questionnaire was used to evaluate patient's satisfaction. Results: Sixty-six patients with pelvic organ prolapse stage 3, including uterine pro-lapse of at least stage 2 (mean point C at+1.4 (range+8-(-1)) were included. Mean follow-up was 22 months. Success rate of the vaginal mesh procedure aimed to repair uterine prolapse was 92% (61/66), with mean point C at −6.7 (range (-1) - (-9)). No major intra-or post-operative complication occurred. A telephone survey questionnaire was conducted post-operatively 28 months on average. Ninety-eight percent of women were satisfied with the decision to preserve their uterus. Eighteen patients (34%) received prior consultation elsewhere for hysterectomy due to their prolapse, and decided to have the operation at our center in order to preserve the uterus. Conclusions: Uterine preservation with vaginal mesh was found to be a safe and effective treatment, even in cases with advanced uterine prolapse. Most patients prefer to keep their uterus. Uterus preservation options should be discussed with every patient before surgery for pelvic organ prolapse. PMID:27564289

  17. The Prevalence and Contents of Advance Directives in Patients With Pacemakers

    PubMed Central

    Pasalic, Dario; Tajouri, Tanya H.; Ottenberg, Abigale L.; Mueller, Paul S.

    2013-01-01

    Background Little is known about the use of advance directives (ADs) in patients who have implantable cardiac pacemakers (PMs). Methods We conducted a retrospective review of the medical records of residents of Olmsted County, Minnesota, who underwent implantation of a cardiac PM at Mayo Clinic (Rochester, Minnesota) during 2006 and 2007 and determined the prevalence and contents of ADs in these patients. Results During the study period, 205 residents of Olmsted County (men, 53%) underwent PM implantation (mean age [SD] at implantation, 77 [15] years). Overall, 120 patients (59%) had ADs. Of these, 63 ADs (53%) were executed more than 12 months before and 33 (28%) were executed after PM implantation. Many patients specifically mentioned life-prolonging treatments in their ADs: cardiopulmonary resuscitation, 76 (63%); mechanical ventilation, 56 (47%); and hemodialysis, 31 (26%). Pain control was mentioned in 79 ADs (66%) and comfort measures were mentioned in 42 ADs (35%). Furthermore, the AD of many patients contained a general statement about end-of-life care (eg, no “heroic measures”). However, only 1 AD (1%) specifically addressed the end-of-life management of the PM. Conclusions More than half of the patients with PMs in our study had executed an AD, but only 1 patient specifically mentioned her PM in her AD. These results suggest that patients with PMs should be encouraged to execute ADs and, specifically address end-of-life device management in their ADs. Doing so may prevent end-of-life ethical dilemmas related to PM management. PMID:24215172

  18. Impact of more detailed categorization of shrinkage or progression ratio at initial imaging response after sorafenib treatment in advanced hepatocellular carcinoma patients

    PubMed Central

    Wada, Yoshiyuki; Takami, Yuko; Tateishi, Masaki; Ryu, Tomoki; Mikagi, Kazuhiro; Saitsu, Hideki

    2015-01-01

    Background Sorafenib therapy improves survival in unresectable hepatocellular carcinoma (HCC) patients without an objective response. The present study investigated whether the initial imaging response might be a prognostic indicator after administration of sorafenib therapy in HCC patients. Patients and methods This retrospective study reviewed unresectable HCC patients undergoing sorafenib therapy. Patients evaluated without complete response, partial response (PR), or progressive disease (PD) at the initial imaging response evaluation by modified Response Evaluation Criteria in Solid Tumors were divided into three groups according to more detailed categorization of the shrinkage/progression ratio in initial imaging response. A comparison of progression-free and overall survival among these groups was performed. Results Of the 43 non-PR non-PD patients with target lesions, ten (23.3%) exhibited mild response (MR; −30% to −5%), 14 (32.6%) exhibited no change (NC; −5% to +5%), and 19 (44.2%) exhibited mild-PD (MPD; +5% to +20%). There was no statistical difference in progression-free or overall survival between MR and NC patients. The median progression-free survivals in NC+MR and mild-PD patients were 15.0 and 5.3 months, respectively (P<0.01), and the median survival times were 31.9 and 17.1 months, respectively (P<0.001). In multivariate analysis, etiology (hepatitis C virus) and initial imaging response (MR+NC) was identified as an independently good prognostic factor. Conclusion More detailed categorization of shrinkage or progression at the initial imaging response evaluation may be a useful marker for predicting sorafenib treatment outcomes in HCC patients. If the initial imaging response is not progression but stability, sorafenib may have a survival benefit. PMID:26586953

  19. Discriminating among degenerative parkinsonisms using advanced (123)I-ioflupane SPECT analyses.

    PubMed

    Badoud, Simon; Van De Ville, Dimitri; Nicastro, Nicolas; Garibotto, Valentina; Burkhard, Pierre R; Haller, Sven

    2016-01-01

    (123)I-ioflupane single photon emission computed tomography (SPECT) is a sensitive and well established imaging tool in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS), yet a discrimination between PD and APS has been considered inconsistent at least based on visual inspection or simple region of interest analyses. We here reappraise this issue by applying advanced image analysis techniques to separate PD from the various APS. This study included 392 consecutive patients with degenerative parkinsonism undergoing (123)I-ioflupane SPECT at our institution over the last decade: 306 PD, 24 multiple system atrophy (MSA), 32 progressive supranuclear palsy (PSP) and 30 corticobasal degeneration (CBD) patients. Data analysis included voxel-wise univariate statistical parametric mapping and multivariate pattern recognition using linear discriminant classifiers. MSA and PSP showed less ioflupane uptake in the head of caudate nucleus relative to PD and CBD, yet there was no difference between MSA and PSP. CBD had higher uptake in both putamen relative to PD, MSA and PSP. Classification was significant for PD versus APS (AUC 0.69, p < 0.05) and between APS subtypes (MSA vs CBD AUC 0.80, p < 0.05; MSA vs PSP AUC 0.69 p < 0.05; CBD vs PSP AUC 0.69 p < 0.05). Both striatal and extra-striatal regions contain classification information, yet the combination of both regions does not significantly improve classification accuracy. PD, MSA, PSP and CBD have distinct patterns of dopaminergic depletion on (123)I-ioflupane SPECT. The high specificity of 84-90% for PD versus APS indicates that the classifier is particularly useful for confirming APS cases. PMID:27489771

  20. Advances in Liposuction: Five Key Principles with Emphasis on Patient Safety and Outcomes

    PubMed Central

    Tabbal, Geo N.; Ahmad, Jamil; Lista, Frank

    2013-01-01

    Summary: Since Illouz’s presentation of a technique for lipoplasty at the 1982 Annual Meeting of the American Society of Plastic and Reconstructive Surgeons, liposuction has become one of the most commonly performed aesthetic surgery procedures. The evolution of liposuction has seen refinements in technique and improvement of patient safety-related standards of care. Based on long-term experience with body contouring surgery, 5 principles of advanced liposuction are presented: preoperative evaluation and planning, intraoperative monitoring—safety measures, the role of wetting solutions and fluid resuscitation, circumferential contouring and complication prevention, and outcomes measurement. PMID:25289270

  1. Acute hypertension during ramucirumab infusion in two patients with advanced oesophagogastric cancer.

    PubMed

    van der Woude, Stephanie O; van Laarhoven, Hanneke W M

    2016-08-18

    Ramucirumab, a monoclonal antibody targeting the vascular endothelial growth factor (VEGF) pathway, in combination with paclitaxel is becoming part of standard second-line systemic therapy for advanced oesophagogastric cancer, based on the results of the REGARD and RAINBOW trials. Common well-known side effects of VEGF pathway inhibitors are hypertension and infusion-related reactions. Here, we describe hypertension as the predominant feature of an infusion-related reaction in 2 patients with metastasised oesophagogastric carcinoma treated with ramucirumab and paclitaxel as second-line treatment and propose possible explanations of this side effect previously undescribed for ramucirumab.

  2. Acute hypertension during ramucirumab infusion in two patients with advanced oesophagogastric cancer.

    PubMed

    van der Woude, Stephanie O; van Laarhoven, Hanneke W M

    2016-01-01

    Ramucirumab, a monoclonal antibody targeting the vascular endothelial growth factor (VEGF) pathway, in combination with paclitaxel is becoming part of standard second-line systemic therapy for advanced oesophagogastric cancer, based on the results of the REGARD and RAINBOW trials. Common well-known side effects of VEGF pathway inhibitors are hypertension and infusion-related reactions. Here, we describe hypertension as the predominant feature of an infusion-related reaction in 2 patients with metastasised oesophagogastric carcinoma treated with ramucirumab and paclitaxel as second-line treatment and propose possible explanations of this side effect previously undescribed for ramucirumab. PMID:27539134

  3. The Attitudes of Chinese Cancer Patients and Family Caregivers toward Advance Directives.

    PubMed

    Zhang, Qiu; Xie, Chuanbo; Xie, Shanghang; Liu, Qing

    2016-01-01

    Advance directives (ADs) have been legislated in many countries to protect patient autonomy regarding medical decisions at the end of life. China is facing a serious cancer burden and cancer patients' quality at the end of life should be a concern. However, limited studies have been conducted locally to gather information about attitudes toward ADs. The purpose of this study was to investigate the attitudes of Chinese cancer patients and family caregivers toward ADs and to explore the predictors that are associated with attitudes. The study indicated that although there was low awareness of ADs, most cancer patients and family caregivers had positive attitudes toward ADs after related information was explained to them. Participants preferred to discuss ADs with medical staff when they were diagnosed with a life-threatening disease. Preferences for refusing life-sustaining treatment and choosing Hospice-Palliative Care (HPC) at the end of life would increase the likelihood of agreeing with ADs. This suggests that some effective interventions to help participants better understand end-of-life treatments are helpful in promoting ADs. Moreover, the development of HPC would contribute to Chinese cancer patients and family caregivers agreeing with ADs. PMID:27529264

  4. Prognostic Impact of Pretreatment Plasma Fibrinogen in Patients with Locally Advanced Oral and Oropharyngeal Cancer

    PubMed Central

    Holzinger, Daniel; Danilovic, Ivan; Seemann, Rudolf; Kornek, Gabriela; Engelmann, Johannes; Pillerstorff, Robert; Holawe, Simone; Psyrri, Amanda; Erovic, Boban M.; Farwell, Gregory; Perisanidis, Christos

    2016-01-01

    Background We aimed to determine the prognostic significance of pretreatment plasma fibrinigen in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). Methods A cohort of 183 patients with locally advanced OOSCC receiving preoperative chemoradiotherapy was retrospectively examined. Using ROC curve analysis, a pretreatment plasma fibrinogen cutoff value of 447mg/dL was determined. The primary endpoints were overall survival and recurrence-free survival. A secondary endpoint was to determine whether pretreatment plasma fibrinogen could predict treatment response to neoadjuvant chemoradiotherapy. Cox regression models and Kaplan–Meier curves were used for survival analyses. Results Seventy-one patients had an elevated pretreatment plasma fibrinogen (fibrinogen >447mg/dL). Patients with high fibrinogen showed significantly higher pathologic stages after neoadjuvant treatment than those with low fibrinogen (p = 0.037). In univariate analysis, elevated fibrinogen was associated with poor overall survival (p = 0.005) and recurrence-free survival (p = 0.008) Multivariate analysis revealed that elevated fibrinogen remained an independent risk factor for death (hazard ratio 1.78, 95% CI 1.09–2.90, p = 0.021) and relapse (hazard ratio 1.78, 95% CI 1.11–2.86, p = 0.016). Conclusion Elevated pretreatment plasma fibrinogen is associated with lack of response to neoadjuvant chemoradiotherapy and reduced OS and RFS in patients with OOSCC. Thus, plasma fibrinogen may emerge as a novel prognostic indicator and a potential therapeutic target in OOSCC. PMID:27362659

  5. A phase I study of indoximod in patients with advanced malignancies

    PubMed Central

    Soliman, Hatem H.; Minton, Susan E.; Han, Hyo Sook; Ismail-Khan, Roohi; Neuger, Anthony; Khambati, Fatema; Noyes, David; Lush, Richard; Chiappori, Alberto A.; Roberts, John D.; Link, Charles; Vahanian, Nicholas N.; Mautino, Mario; Streicher, Howard; Sullivan, Daniel M.; Antonia, Scott J.

    2016-01-01

    Purpose Indoximod is an oral inhibitor of the indoleamine 2,3-dioxygenase pathway, which causes tumor-mediated immunosuppression. Primary endpoints were maximum tolerated dose (MTD) and toxicity for indoximod in patients with advanced solid tumors. Secondary endpoints included response rates, pharmacokinetics, and immune correlates. Experimental Design Our 3+3 phase I trial comprised 10 dose levels (200, 300, 400, 600, and 800 mg once/day; 600, 800, 1200, 1600, and 2000 mg twice/day). Inclusion criteria were measurable metastatic solid malignancy, age ≥18 years, and adequate organ/marrow function. Exclusion criteria were chemotherapy ≤ 3 weeks prior, untreated brain metastases, autoimmune disease, or malabsorption. Results In 48 patients, MTD was not reached at 2000 mg twice/day. At 200 mg once/day, 3 patients previously treated with checkpoint inhibitors developed hypophysitis. Five patients showed stable disease >6 months. Indoximod plasma AUC and Cmax plateaued above 1200mg. Cmax (∼12 μM at 2000 mg twice/day) occurred at 2.9 hours, and half-life was 10.5 hours. C reactive protein (CRP) levels increased across multiple dose levels. Conclusions Indoximod was safe at doses up to 2000 mg orally twice/day. Best response was stable disease >6 months in 5 patients. Induction of hypophysitis, increased tumor antigen autoantibodies and CRP levels were observed. PMID:27008709

  6. Phase 1 Study of Intravenous Oncolytic Poxvirus (vvDD) in Patients With Advanced Solid Cancers

    PubMed Central

    Downs-Canner, Stephanie; Guo, Zong Sheng; Ravindranathan, Roshni; Breitbach, Caroline J; O'Malley, Mark E; Jones, Heather L; Moon, Anne; McCart, Judith Andrea; Shuai, Yongli; Zeh, Herbert J; Bartlett, David L

    2016-01-01

    We have conducted a phase 1 study of intravenous vvDD, a Western Reserve strain oncolytic vaccinia virus, on 11 patients with standard treatment-refractory advanced colorectal or other solid cancers. The primary endpoints were maximum tolerated dose and associated toxicity while secondary endpoints were pharmacokinetics, pharmacodynamics, immune responses, and antitumor activity. No dose-limiting toxicities and treatment related severe adverse events were observed. The most common adverse events were grades 1/2 flu-like symptoms. Virus genomes were detectable in the blood 15–30 minutes after virus administration in a dose-dependent manner. There was evidence of a prolonged virus replication in tumor tissues in two patients, but no evidence of virus replication in non-tumor tissues, except a healed injury site and an oral thrush. Over 100-fold of anti-viral antibodies were induced in patients' sera. A strong induction of inflammatory and Th1, but not Th2 cytokines, suggested a potent Th1-mediated immunity against the virus and possibly the cancer. One patient showed a mixed response on PET-CT with resolution of some liver metastases, and another patient with cutaneous melanoma demonstrated clinical regression of some lesions. Given the confirmed safety, further trials evaluating intravenous vvDD in combination with therapeutic transgenes, immune checkpoint blockade or complement inhibitors, are warranted. PMID:27203445

  7. Efficacy of a self-management plan in exacerbations for patients with advanced COPD

    PubMed Central

    Sánchez-Nieto, Juan Miguel; Andújar-Espinosa, Rubén; Bernabeu-Mora, Roberto; Hu, Chunshao; Gálvez-Martínez, Beatriz; Carrillo-Alcaraz, Andrés; Álvarez-Miranda, Carlos Federico; Meca-Birlanga, Olga; Abad-Corpa, Eva

    2016-01-01

    Background Self-management interventions improve different outcome variables in various chronic diseases. Their role in COPD has not been clearly established. We assessed the efficacy of an intervention called the self-management program on the need for hospital care due to disease exacerbation in patients with advanced COPD. Methods Multicenter, randomized study in two hospitals with follow-up of 1 year. All the patients had severe or very severe COPD, and had gone to either an accident and emergency (A&E) department or had been admitted to a hospital at least once in the previous year due to exacerbation of COPD. The intervention consisted of a group education session on the main characteristics of the disease, an individual training session on inhalation techniques, at the start and during the 3rd month, and a written action plan containing instructions for physical activity and treatment for stable phases and exacerbations. We determined the combined number of COPD-related hospitalizations and emergency visits per patient per year. Secondary endpoints were number of patients with visits to A&E and the number of patients hospitalized because of exacerbations, use of antibiotics and corticosteroids, length of hospital stay, and all-cause mortality. Results After 1 year, the rate of COPD exacerbations with visits to A&E or hospitalization had decreased from 1.37 to 0.89 (P=0.04) and the number of exacerbations dropped from 52 to 42 in the group of patients who received the intervention. The numbers of patients hospitalized, at 19 (40.4%) versus 20 (52.6%) (P=0.26), and those who went to A&E, at 9 (19.1%) versus 14 (36.8%) (P=0.06), due to exacerbation of COPD were also lower in this group. Intake of antibiotics was higher in the intervention group, whereas use of glucocorticoids was slightly lower, though there were no significant differences (P=0.30). There were also no differences between groups in the length of hospital stay (P=0.154) or overall mortality (P=0

  8. [Application of chemiluminescence immunoassay method in detection of serum index for liver fibrosis in patients with advanced schistosomiasis].

    PubMed

    Luo, Jiang-Long

    2011-02-01

    The method of chemiluminescence immunoassay (CLIA) was adopted to detect the levels of hyaluronic acid (HA), laminin (LN), III procollagen (CP III), IV collagen (IV-C) in the sera of 102 cases of advanced schistosomiasis. The results showed that the levels of the 4 indexes of advanced schistosomiasis patients were significantly higher than those of healthy people. It is suggested that the application of CLIA to detect the related serum indexes in patients with advanced schistosomiasis is useful in the diagnosis of liver fibrosis. PMID:22164394

  9. Combination chemotherapy followed by surgery or radiotherapy in patients with locally advanced cervical cancer.

    PubMed

    Kirsten, F; Atkinson, K H; Coppleson, J V; Elliott, P M; Green, D; Houghton, R; Murray, J C; Russell, P; Solomon, H J; Friedlander, M

    1987-06-01

    Forty-seven patients with locally advanced cervical cancer at high risk of relapse received three cycles of chemotherapy with PVB (cisplatin, vinblastine and bleomycin) before definitive local treatment with either radical surgery or radiotherapy. Thirty-one of the 47 patients (66%) responded to initial chemotherapy, and 11 of them have relapsed compared with 13 of the 16 non-responders. Median time to recurrence was 31 weeks for PVB non-responders but has not yet been reached for PVB responders. After a median follow-up of 128 weeks, 14 of the 31 responders (45%) are alive and disease free compared with 3 of the 16 non-responders (19%). There was a positive correlation between response to chemotherapy and subsequent response to radiotherapy. PVB was in general well tolerated although one death is probably attributable to chemotherapy. A randomized study comparing radiotherapy alone with initial PVB chemotherapy followed by radiotherapy is in progress. PMID:2441736

  10. Effectiveness of prophylactic retropharyngeal lymph node irradiation in patients with locally advanced head and neck cancer

    PubMed Central

    2012-01-01

    Background The aim of the study is to assess the effectiveness of intensity-modulated radiotherapy (IMRT) or image-guided radiotherapy (IGRT) for the prevention of retropharyngeal nodal recurrences in locally advanced head and neck cancer. Methods A retrospective review of 76 patients with head and neck cancer undergoing concurrent chemoradiation or postoperative radiotherapy with IMRT or IGRT who were at risk for retropharyngeal nodal recurrences because of anatomic site (hypopharynx, nasopharynx, oropharynx) and/or the presence of nodal metastases was undertaken. The prevalence of retropharyngeal nodal recurrences was assessed on follow-up positron emission tomography (PET)-CT scans. Results At a median follow-up of 22 months (4–53 months), no patient developed retropharyngeal nodal recurrences. Conclusion Prophylactic irradiation of retropharyngeal lymph nodes with IMRT or IGRT provides effective regional control for individuals at risk for recurrence in these nodes. PMID:22708791

  11. Bilateral ureteral complete obstruction with huge spontaneous urinoma formation in a patient with advanced bladder cancer.

    PubMed

    Jou, Yeong-Chin; Shen, Cheng-Huang; Cheng, Ming-Chin; Lin, Chang-Te; Chen, Pi-Che

    2012-02-01

    Spontaneous rupture of the collecting system with extravasation of urine and urinoma formation is usually associated with urinary tract obstruction by a ureteral calculus. Tumor growth is an extremely rare cause of urinary extravasation. Here we report a case of bilateral obstructive uropathy with a huge spontaneous left retroperitoneal urinoma caused by advanced infiltrative transitional cell carcinoma of the urinary bladder. The point of leakage was located in the left renal pelvis. The urinary leakage ceased after percutaneous nephrostomy drainage, and the patient subsequently underwent radical cystoprostatectomy. Histopathology revealed a high-grade urothelial carcinoma of the urinary bladder with pelvic lymph node metastasis. The patient refused any adjuvant treatment and expired 6 months after the operation from disseminated metastasis from bladder cancer.

  12. Determinants of Quality Care and Mortality for Patients With Locally Advanced Cervical Cancer in Virginia

    PubMed Central

    Showalter, Timothy N.; Camacho, Fabian; Cantrell, Leigh A.; Anderson, Roger T.

    2016-01-01

    Abstract Outcomes for patients with locally advanced cervical cancer are influenced by receipt of all indicated components of quality care: early diagnosis and receipt of external beam radiation therapy, chemotherapy, and brachytherapy. We performed an observational cohort study to evaluate receipt of quality cancer care and mortality after cancer diagnosis among patients with locally advanced cervical cancer in Virginia. We queried the Virginia state cancer registry to identify patients with International Federation of Gynecology and Obstetrics Stage IB-IVA cervical cancer who were diagnosed during 2002 to 2012. We evaluated the influence of tumor-related, demographic, and geospatial factors on the receipt of indicated therapies and mortality. Treatment quality score of 0 to 3 was defined based upon the extent of receipt of the components of indicated therapy. A total of 1048 patients were identified; 33.1% received all 3 components of treatment and only 54.0% received brachytherapy. Predictors of higher quality score included younger age group versus 66+ years at diagnosis (18–42 odds ratio [OR] = 12.3, 95% confidence interval: 6.6, 23.0; 42–53 OR = 5.6, CI: 3.3, 9.5; 53–66 OR = 5.5, CI: 3.3, 9.1), lower tumor stages versus IVA (IB2 OR = 3.3, CI: 1.8, 6.2; II OR = 2.7, CI: 1.6, 4.5; IIIx OR = 2.1, CI: 1.3, 3.6), and treatment at a high-volume facility (OR 2.2, CI: 1.2, 4.2). Predictors of increased mortality included earlier year of diagnosis, higher tumor stage, treatment at a lower volume facility, and lower treatment quality score. In a cohort of locally advanced cervical cancer patients in Virginia, we identified a low rate of receipt of complete quality care for cervical cancer and a strong effect of facility volume on quality treatment and survival. Further research is needed to develop strategies to improve access to quality treatment and outcomes for cervical cancer. PMID:26937934

  13. Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma

    PubMed Central

    Lyford-Pike, Sofia; Peng, Shiwen; Young, Geoffrey D.; Taube, Janis M.; Westra, William H.; Akpeng, Belinda; Bruno, Tullia C.; Richmon, Jeremy D.; Wang, Hao; Bishop, Justin A.; Chen, Lieping; Drake, Charles G.; Topalian, Suzanne L.; Pardoll, Drew M.; Pai, Sara I.

    2013-01-01

    Human papillomavirus-associated head and neck squamous cell carcinomas (HPV-HNSCC) originate in the tonsils, the major lymphoid organ that orchestrates immunity to oral infections. Despite its location, the virus escapes immune elimination during malignant transformation and progression. Here, we provide evidence for the role of the PD-1:PD-L1 pathway in HPV-HNSCC immune resistance. We demonstrate membranous expression of PD-L1 in the tonsillar crypts, the site of initial HPV infection. In HPV-HNSCCs that are highly infiltrated with lymphocytes, PD-L1 expression on both tumor cells and CD68+ tumor associated macrophages (TAMs) is geographically localized to sites of lymphocyte fronts, while the majority of CD8+ tumor infiltrating lymphocytes (TILs) express high levels of PD-1, the inhibitory PD-L1 receptor. Significant levels of mRNA for interferon-γ (IFN-γ), a major cytokine inducer of PD-L1 expression, were found in HPV+ PD-L1(+) tumors. Our findings support the role of the PD-1:PD-L1 interaction in creating an “immune-privileged” site for initial viral infection and subsequent adaptive immune resistance once tumors are established and suggest a rationale for therapeutic blockade of this pathway in patients with HPV-HNSCC. PMID:23288508

  14. Friction Coefficient and Superficial Zone Protein are Increased in Patients with Advanced Osteoarthritis

    PubMed Central

    Neu, C.P.; Reddi, A.H.; Komvopoulos, K.; Schmid, T.M.; Di Cesare, P.E.

    2010-01-01

    Objective To quantify the concentration of superficial zone protein (SZP) in articular cartilage and synovial fluid of patients with advanced osteoarthritis (OA), and to further correlate the SZP content with the friction coefficient, OA severity, and levels of inflammatory cytokines. Methods Samples of articular cartilage and synovial fluid were obtained from patients undergoing elective total knee replacement surgery. Additional normal samples were obtained from donated body program and tissue bank sources. Regional SZP expression in cartilage obtained from the femoral condyles was quantified by enzyme-linked immunosorbant assay and visualized by immunohistochemistry. Friction coefficient measurements were obtained from cartilage plugs slid in the boundary lubrication regime. OA severity was graded using histochemical analyses. The concentration of SZP and inflammatory cytokines in synovial fluid were determined by enzyme-linked immunosorbant assays. Results A pattern of SZP localization in knee cartilage was identified, with load-bearing regions exhibiting high SZP expression. SZP patterns correlated to friction coefficient and OA severity; however SZP expression was observed in all samples at the articular surface, regardless of OA severity. SZP expression and aspirate volume of synovial fluid were higher in OA patients compared to normal controls. Expressions of cytokines were elevated in the synovial fluid of some patients. Conclusion The results reveal a mechano-chemical coupling in which physical forces regulate OA severity and joint lubrication. The findings of this study also suggest that SZP may be ineffective in reducing joint friction in the boundary lubrication regime at an advanced OA stage where other mechanisms may dominate the observed tribological behavior. PMID:20499384

  15. Surprise Questions for Survival Prediction in Patients With Advanced Cancer: A Multicenter Prospective Cohort Study

    PubMed Central

    Hamano, Jun; Morita, Tatsuya; Inoue, Satoshi; Ikenaga, Masayuki; Matsumoto, Yoshihisa; Sekine, Ryuichi; Yamaguchi, Takashi; Hirohashi, Takeshi; Tajima, Tsukasa; Tatara, Ryohei; Watanabe, Hiroaki; Otani, Hiroyuki; Takigawa, Chizuko; Matsuda, Yoshinobu; Nagaoka, Hiroka; Mori, Masanori; Yamamoto, Naoki; Shimizu, Mie; Sasara, Takeshi

    2015-01-01

    Background. Predicting the short-term survival in cancer patients is an important issue for patients, family, and oncologists. Although the prognostic accuracy of the surprise question has value in 1-year mortality for cancer patients, the prognostic value for short-term survival has not been formally assessed. The primary aim of the present study was to assess the prognostic value of the surprise question for 7-day and 30-day survival in patients with advanced cancer. Patients and Methods. The present multicenter prospective cohort study was conducted in Japan from September 2012 through April 2014, involving 16 palliative care units, 19 hospital-based palliative care teams, and 23 home-based palliative care services. Results. We recruited 2,425 patients and included 2,361 for analysis: 912 from hospital-based palliative care teams, 895 from hospital palliative care units, and 554 from home-based palliative care services. The sensitivity, specificity, positive predictive value, and negative predictive value of the 7-day survival surprise question were 84.7% (95% confidence interval [CI], 80.7%–88.0%), 68.0% (95% CI, 67.3%–68.5%), 30.3% (95% CI, 28.9%–31.5%), and 96.4% (95% CI, 95.5%–97.2%), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for the 30-day surprise question were 95.6% (95% CI, 94.4%–96.6%), 37.0% (95% CI, 35.9%–37.9%), 57.6% (95% CI, 56.8%–58.2%), and 90.4% (95% CI, 87.7%–92.6%), respectively. Conclusion. Surprise questions are useful for screening patients for short survival. However, the high false-positive rates do not allow clinicians to provide definitive prognosis prediction. Implications for Practice: The findings of this study indicate that clinicians can screen patients for 7- or 30-day survival using surprise questions with 90% or more sensitivity. Clinicians cannot provide accurate prognosis estimation, and all patients will not always die within the defined periods. The

  16. Advance Directives and Communication Skills of Prehospital Physicians Involved in the Care of Cardiovascular Patients.

    PubMed

    Gigon, Fabienne; Merlani, Paolo; Ricou, Bara

    2015-12-01

    Advance directives (AD) were developed to respect patient autonomy. However, very few patients have AD, even in cases when major cardiovascular surgery is to follow. To understand the reasons behind the low prevalence of AD and to help decision making when patients are incompetent, it is necessary to focus on the impact of prehospital practitioners, who may contribute to an increase in AD by discussing them with patients. The purpose of this study was to investigate self-rated communication skills and the attitudes of physicians potentially involved in the care of cardiovascular patients toward AD.Self-administered questionnaires were sent to general practitioners, cardiologists, internists, and intensivists, including the Quality of Communication Score, divided into a General Communication score (QOCgen 6 items) and an End-of-life Communication score (QOCeol 7 items), as well as questions regarding opinions and practices in terms of AD.One hundred sixty-four responses were received. QOCgen (mean (±SD)): 9.0/10 (1.0); QOCeol: 7.2/10 (1.7). General practitioners most frequently start discussions about AD (74/149 [47%]) and are more prone to designate their own specialty (30/49 [61%], P < 0.0001). Overall, only 57/159 (36%) physicians designated their own specialty; 130/158 (82%) physicians ask potential cardiovascular patients if they have AD and 61/118 (52%) physicians who care for cardiovascular patients talk about AD with some of them.The characteristics of physicians who do not talk about AD with patients were those who did not personally have AD and those who work in private practices.One hundred thirty-three (83%) physicians rated the systematic mention of patients' AD in the correspondence between physicians as good, while 114 (71%) at the patients' first registration in the private practice.Prehospital physicians rated their communication skills as good, whereas end-of-life communication was rated much lower. Only half of those surveyed speak about AD

  17. Nutritional rehabilitation in patients with advanced head and neck cancer receiving radiation therapy.

    PubMed

    Daly, J M; Hearne, B; Dunaj, J; LePorte, B; Vikram, B; Strong, E; Green, M; Muggio, F; Groshen, S; DeCosse, J J

    1984-10-01

    maintained mean mid-arm circumference and recovered mean serum albumin levels after radiation therapy in contrast with the orally fed group. Intensive outpatient tube-feeding nutritional support during radiation therapy in patients with advanced inoperable squamous cancer of the oropharynx significantly improved mean weight maintenance, mean caloric and protein intake, and mean serum albumin levels compared with patients who received optimal oral nutrition. Tumor response to radiation therapy, however, was unchanged.

  18. Autonomic and cognitive functions in Parkinson's disease (PD).

    PubMed

    Oh, Eung Seok; Lee, Ji Hee; Seo, Jin Gi; Sohn, Eun Hee; Lee, Ae Young

    2011-01-01

    We performed this study to evaluate the relationship between the stages of PD and autonomic dysfunction, and to find an association between the autonomic dysfunction and cognitive impairment in PD. Sixty-three patients who met the criteria of the United Kingdom PD Society Brain Bank were enrolled prospectively. Clinical stages were using the Hoehn and Yahr (H&Y) staging and unified PD rating scale motor scores. Cognitive functions were evaluated using the mini-mental state examination (MMSE) and the modified MMSE (3MS) test. The scale for outcome in PD-autonomic (SCOPA-AUT) was used to evaluate autonomic symptoms. Severities of autonomic dysfunction were classified using the composite autonomic scoring scale (CASS). Fifty-four of the 63 patients (86%) had shown abnormalities on CASS. H&Y stages correlated with SCOPA-AUT (p<0.05) and 3MS and MMSE scores (p<0.05). H&Y stages were positively related with autonomic dysfunction, heart rate ratios during deep breathing and the quantitative sudomotor axon reflex test (QSART) scores. Autonomic dysfunction may be present from disease onset, whereas the rate of cognitive decline increases with disease progression. We recommend that both qualitative and quantitative autonomic evaluation from the early stage of disease and regular cognitive screening with disease progression might be useful to facilitate optimal management in PD.

  19. Advance statement of consent from patients with primary CNS tumours to organ donation and elective ventilation.

    PubMed

    Patel, Umang Jash

    2013-03-01

    A deficit in the number of organs available for transplantation persists even with an increase in donation rates. One possible choice of donor for organs that appears under-referred and/or unaccepted is patients with primary brain tumours. In spite of advances in the treatment of high-grade primary central nervous system (CNS) tumours, the prognosis remains dire. A working group on organs from donors with primary CNS tumours showed that the risk of transmission is small and outweighs the benefits of waiting for a normal donor, in survival and organ life-years, with caveats. This paper explores the possibility that, if information on organ donation were made available to patients and their families with knowledge of their inevitable fate, perhaps some will choose to donate. It would be explained that to achieve this, elective ventilation would be performed in their final moments. This would obviate the consent question because of an advance statement. It is accepted that these are sensitive matters and there will be logistic issues. This will need discussion with the public and other professionals, but it could increase the number of donors and can be extrapolated to encompass other primary CNS tumours. PMID:23303178

  20. Coping strategies for existencial and spiritual suffering in Israeli patients with advanced cancer

    PubMed Central

    2014-01-01

    Coping with existential and spiritual concerns is inescapable in end-of-life care although not enough is known about the strategies and mechanisms involved. This pilot study focused on identifying the strategies for coping with existential and spiritual suffering at the end of life of secular Jews with advanced-stage cancer. Using the phenomenological approach to data collection, in-depth interviews were conducted with 22 patients receiving symptom relief care at a daycare oncology clinic. The interviews were recorded and transcribed verbatim, and the content was analyzed. Advanced-stage cancer patients employ several approaches to cope with existential and spiritual concerns. The themes emerging from the interviews present five dimensions of coping strategies: openness and choosing to face reality, connectedness and the significance of family, pursuit of meaning, the connection of body, mind and spirit and, lastly, humor and a positive outlook. Conclusions Since these concerns cause suffering and distress, intervention models targeting existential and spiritual suffering should be disseminated among professionals involved in caring for people with life-threatening illnesses. PMID:24984840

  1. Prognosis and Clinicopathologic Features of Patients With Advanced Stage Isocitrate Dehydrogenase (IDH) Mutant and IDH Wild-Type Intrahepatic Cholangiocarcinoma

    PubMed Central

    Goyal, Lipika; Govindan, Aparna; Sheth, Rahul A.; Nardi, Valentina; Blaszkowsky, Lawrence S.; Faris, Jason E.; Clark, Jeffrey W.; Ryan, David P.; Kwak, Eunice L.; Allen, Jill N.; Murphy, Janet E.; Saha, Supriya K.; Hong, Theodore S.; Wo, Jennifer Y.; Ferrone, Cristina R.; Tanabe, Kenneth K.; Chong, Dawn Q.; Deshpande, Vikram; Borger, Darrell R.; Iafrate, A. John; Bardeesy, Nabeel; Zheng, Hui

    2015-01-01

    Background. Conflicting data exist regarding the prognostic impact of the isocitrate dehydrogenase (IDH) mutation in intrahepatic cholangiocarcinoma (ICC), and limited data exist in patients with advanced-stage disease. Similarly, the clinical phenotype of patients with advanced IDH mutant (IDHm) ICC has not been characterized. In this study, we report the correlation of IDH mutation status with prognosis and clinicopathologic features in patients with advanced ICC. Methods. Patients with histologically confirmed advanced ICC who underwent tumor mutational profiling as a routine part of their care between 2009 and 2014 were evaluated. Clinical and pathological data were collected by retrospective chart review for patients with IDHm versus IDH wild-type (IDHwt) ICC. Pretreatment tumor volume was calculated on computed tomography or magnetic resonance imaging. Results. Of the 104 patients with ICC who were evaluated, 30 (28.8%) had an IDH mutation (25.0% IDH1, 3.8% IDH2). The median overall survival did not differ significantly between IDHm and IDHwt patients (15.0 vs. 20.1 months, respectively; p = .17). The pretreatment serum carbohydrate antigen 19-9 (CA19-9) level in IDHm and IDHwt patients was 34.5 and 118.0 U/mL, respectively (p = .04). Age at diagnosis, sex, histologic grade, and pattern of metastasis did not differ significantly by IDH mutation status. Conclusion. The IDH mutation was not associated with prognosis in patients with advanced ICC. The clinical phenotypes of advanced IDHm and IDHwt ICC were similar, but patients with IDHm ICC had a lower median serum CA19-9 level at presentation. Implications for Practice: Previous studies assessing the prognostic impact of the isocitrate dehydrogenase (IDH) gene mutation in intrahepatic cholangiocarcinoma (ICC) mainly focused on patients with early-stage disease who have undergone resection. These studies offer conflicting results. The target population for clinical trials of IDH inhibitors is patients with

  2. Neurological Adverse Effects in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX

    PubMed Central

    Najam, Rahila; Mateen, Ahmed

    2013-01-01

    The study is designed to assess the frequency and severity of few dose limiting neurological adverse effects of four different schedules of FOLFOX. Patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study. Toxicity was graded according to CTC v 2.0. The frequency of grade 3 and 4 adverse effects was comparatively assessed in each treatment arm. The difference in the pattern of toxicity between the treatment schedule was evaluated. The most frequent adverse symptom of neurological adverse effect was grade 1 paresthesia in the patients treated with FOLFOX4 schedule. Grade 4 peripheral neuropathy was reported in few patients of FOLFOX7 treatment arm. Frequency and onset of neurological adverse effects like paresthesia, dizziness, and hypoesthesia were significantly different (P < 0.05), whereas frequency and onset of peripheral neuropathy were highly significant (P < 0.01) in each treatment arm of FOLFOX. Peripheral neuropathy was associated with electrolyte imbalance and diabetes in few patients. Frequency of symptoms, for example, paresthesia, is associated with increased number of recurrent exposure to oxaliplatin (increased number of cycles) even at low doses (85 mg/m2), whereas severity of symptoms, for example, peripheral neuropathy, is associated with higher dose (130 mg/m2) after few treatment cycles. PMID:24187619

  3. Neurological Adverse Effects in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX.

    PubMed

    Bano, Nusrat; Najam, Rahila; Mateen, Ahmed

    2013-01-01

    The study is designed to assess the frequency and severity of few dose limiting neurological adverse effects of four different schedules of FOLFOX. Patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study. Toxicity was graded according to CTC v 2.0. The frequency of grade 3 and 4 adverse effects was comparatively assessed in each treatment arm. The difference in the pattern of toxicity between the treatment schedule was evaluated. The most frequent adverse symptom of neurological adverse effect was grade 1 paresthesia in the patients treated with FOLFOX4 schedule. Grade 4 peripheral neuropathy was reported in few patients of FOLFOX7 treatment arm. Frequency and onset of neurological adverse effects like paresthesia, dizziness, and hypoesthesia were significantly different (P < 0.05), whereas frequency and onset of peripheral neuropathy were highly significant (P < 0.01) in each treatment arm of FOLFOX. Peripheral neuropathy was associated with electrolyte imbalance and diabetes in few patients. Frequency of symptoms, for example, paresthesia, is associated with increased number of recurrent exposure to oxaliplatin (increased number of cycles) even at low doses (85 mg/m(2)), whereas severity of symptoms, for example, peripheral neuropathy, is associated with higher dose (130 mg/m(2)) after few treatment cycles.

  4. Indium-111-antimyosin scintigraphy after doxorubicin therapy in patients with advanced breast cancer

    SciTech Connect

    Estorch, M.; Carrio, I.; Berna, L.; Martinez-Duncker, C.; Alonso, C.; Germa, J.R.; Ojeda, B. )

    1990-12-01

    Indium-111-antimyosin ({sup 111}In-antimyosin) scans were performed in 20 women with advanced breast cancer after 10 cycles of chemotherapy consisting of cyclophosphamide, 5-fluorouracil and doxorubicin (total cumulative dose of doxorubicin of 500 mg/m2). Antimyosin uptake in the myocardium was quantified by means of a heart-to-lung ratio (HLR). Antimyosin uptake in the myocardium was observed in 17/20 (85%) patients, and HLR after chemotherapy was 1.86 +/- 0.25. Left ventricular ejection fraction (EF) was determined before and after chemotherapy. Patients with decreased EF (8/20, 40%) presented with more intense antimyosin uptake (HLR of 2.11 +/- 0.10 versus 1.70 +/- 0.16 (p = 0.01)). HLR values correlated with EF values after chemotherapy (r = -0.47, p less than 0.05). Positive antimyosin studies after chemotherapy including doxorubicin, indicate the presence of myocardial damage in these patients. Antimyosin studies are a sensitive method to detect myocyte damage in patients after doxorubicin therapy.

  5. 193 nm excimer laser sclerostomy in pseudophakic patients with advanced open angle glaucoma.

    PubMed Central

    Allan, B D; van Saarloos, P P; Cooper, R L; Constable, I J

    1994-01-01

    A modified open mask system incorporating an en face air jet to dry the target area during ablation and a conjunctival plication mechanism, which allows ab externo delivery of the 193 nm excimer laser without prior conjunctival dissection, has been developed to form small bore sclerostomies accurately and atraumatically. Full thickness sclerostomies, and sclerostomies guarded by a smaller internal ostium can be created. A pilot therapeutic trial was conducted in pseudophakic patients with advanced open angle glaucoma. Six full thickness sclerostomies (200 microns and 400 microns diameter) and three guarded sclerostomies were created in nine patients by 193 nm excimer laser ablation (fluence per pulse 400 mJ/cm2, pulse rate 16 Hz, air jet pressure intraocular pressure +25 mm Hg). After 6 months' follow up, intraocular pressure was controlled (< or = 16 mm Hg) in eight of the nine patients (6/9 without medication). Early postoperative complications included hyphaema (trace--2.5 mm) (6/9), temporary fibrinous sclerostomy occlusion (4/9), profound early hypotony (all patients without fibrinous occlusion), and suprachoroidal haemorrhage in one case. Conjunctival laser wounds were self sealing. Small bore laser sclerostomy procedures are functionally equivalent to conventional full thickness procedures, producing early postoperative hypotony, with an increased risk of suprachoroidal haemorrhage in association with this. Further research is required to improve control over internal guarding in excimer laser sclerostomy before clinical trials of this technique can safely proceed. Images PMID:8148335

  6. Longitudinal Temporal and Probabilistic Prediction of Survival in a Cohort of Patients With Advanced Cancer

    PubMed Central

    Perez-Cruz, Pedro E.; dos Santos, Renata; Silva, Thiago Buosi; Crovador, Camila Souza; Nascimento, Maria Salete de Angelis; Hall, Stacy; Fajardo, Julieta; Bruera, Eduardo; Hui, David

    2014-01-01

    Context Survival prognostication is important during end-of-life. The accuracy of clinician prediction of survival (CPS) over time has not been well characterized. Objectives To examine changes in prognostication accuracy during the last 14 days of life in a cohort of patients with advanced cancer admitted to two acute palliative care units and to compare the accuracy between the temporal and probabilistic approaches. Methods Physicians and nurses prognosticated survival daily for cancer patients in two hospitals until death/discharge using two prognostic approaches: temporal and probabilistic. We assessed accuracy for each method daily during the last 14 days of life comparing accuracy at day −14 (baseline) with accuracy at each time point using a test of proportions. Results 6718 temporal and 6621 probabilistic estimations were provided by physicians and nurses for 311 patients, respectively. Median (interquartile range) survival was 8 (4, 20) days. Temporal CPS had low accuracy (10–40%) and did not change over time. In contrast, probabilistic CPS was significantly more accurate (p<.05 at each time point) but decreased close to death. Conclusion Probabilistic CPS was consistently more accurate than temporal CPS over the last 14 days of life; however, its accuracy decreased as patients approached death. Our findings suggest that better tools to predict impending death are necessary. PMID:24746583

  7. Care at home of the patient with advanced multiple sclerosis--part 2.

    PubMed

    Reitman, Nancy Clayton

    2010-05-01

    Clinicians caring for patients with advanced MS have choices of different options and approaches. Whatever path is chosen, interventions must incorporate the wishes and capabilities of the patient and be supported by the care team, usually led by the nurse. As the work of the great psychologist Abraham Maslow has shown, in his famous "hierarchy of needs," the basic levels of needs must be met before the highest self-actualization can be accomplished (Maslow, 1943). This is equally true in the nursing care of very ill patients, as authors Zalenski and Raspa write: "The five levels of the hierarchy of needs as adapted to palliative care are: (1) distressing symptoms, such as pain or dyspnea; (2) fears for physical safety, of dying or abandonment; (3) affection, love and acceptance in the face of devastating illness; (4) esteem, respect, and appreciation for the person; (5) self-actualization and transcendence. Maslow's modified hierarchy of palliative care needs could be utilized to provide a comprehensive approach for the assessment of patients' needs and the design of interventions to achieve goals that start with comfort and potentially extend to the experience of transcendence."(Zalenski & Raspa, 2006, p.1120). PMID:20463509

  8. Significance of symptom clustering in palliative care of advanced cancer patients.

    PubMed

    Tsai, Jaw-Shiun; Wu, Chih-Hsun; Chiu, Tai-Yuan; Chen, Ching-Yu

    2010-04-01

    Patients with advanced cancer often experience multiple concurrent symptoms. To explore this symptom clustering and its associated parameters, we prospectively surveyed 427 consecutive patients on admission to the Palliative Care Unit. There were 222 males (52.0%) and 205 females (48.0%), with a median age of 66 years (range: 27-93 years). The main tumor sites were lung (19.9%), liver (18.0%), and colorectum (11.0%). The median survival was 13 days (1-418 days). Symptoms were assessed using a face-valid Symptom Reporting Form. We identified five symptom clusters by exploratory factor analysis. Clusters were named "loss of energy," "poor intake," "autonomic dysfunction," "aerodigestive impairment," and "pain complex." We used nonhierarchical cluster analysis to divide the 394 patients with complete data into six groups. Each group was characterized by a particular pattern that was composed of different symptom clusters. Survival, functional performance, bone metastasis, and fluid accumulation were significantly associated with symptom clustering in six groups of patients. The severity of psychological distress also related to their physical deterioration. These data suggest that different underlying mechanisms associate with symptom clustering. Further elucidation of these processes may assist in symptom management. PMID:20226623

  9. Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours

    PubMed Central

    Bahleda, Rastislav; Hollebecque, Antoine; Varga, Andrea; Gazzah, Anas; Massard, Christophe; Deutsch, Eric; Amellal, Nadia; Farace, Françoise; Ould-Kaci, Mahmoud; Roux, Flavien; Marzin, Kristell; Soria, Jean-Charles

    2015-01-01

    Background: This Phase I study evaluated continuous- and intermittent-dosing (every other week) of afatinib plus nintedanib in patients with advanced solid tumours. Methods: In the dose-escalation phase (n=45), maximum tolerated doses (MTDs) were determined for continuous/intermittent afatinib 10, 20, 30 or 40 mg once daily plus continuous nintedanib 150 or 200 mg twice daily. Secondary objectives included safety and efficacy. Clinical activity of continuous afatinib plus nintedanib at the MTD was further evaluated in an expansion phase (n=25). Results: The most frequent dose-limiting toxicities were diarrhoea (11%) and transaminase elevations (7%). Maximum tolerated doses were afatinib 30 mg continuously plus nintedanib 150 mg, and afatinib 40 mg intermittently plus nintedanib 150 mg. Treatment-related adverse events (mostly Grade ⩽3) included diarrhoea (98%), asthenia (64%), nausea (62%) and vomiting (60%). In the dose-escalation phase, two patients had partial responses (PRs) and 27 (60%) had stable disease (SD). In the expansion phase, one complete response and three PRs were observed (all non-small cell lung cancer), with SD in 13 (52%) patients. No pharmacokinetic interactions were observed. Conclusions: MTDs of continuous or intermittent afatinib plus nintedanib demonstrated a manageable safety profile with proactive management of diarrhoea. Antitumour activity was observed in patients with solid tumours. PMID:26512876

  10. Glycated Hemoglobin and Outcomes in Patients with Advanced Diabetic Chronic Kidney Disease

    PubMed Central

    Kuo, I-Ching; Lin, Hugo You-Hsien; Niu, Sheng-Wen; Hwang, Daw-Yang; Lee, Jia-Jung; Tsai, Jer-Chia; Hung, Chi-Chih; Hwang, Shang-Jyh; Chen, Hung-Chun

    2016-01-01

    Diabetes is the major risk factor for end-stage renal disease (ESRD) worldwide. In advanced chronic kidney disease (CKD), less is known about the predictive value of HbA1c. We enrolled 2401 diabetic patients with stage 3–4 and stage 5 CKD, who were classified into 4 groups according to their baseline HbA1c values (<6%, 6%–7%, 7%–9%, and >9%). During the median follow-up of 3 years, 895 patients developed ESRD, and 530 died. In linear regression analysis, higher HbA1c correlated with higher eGFR in patients with stage 5 CKD but not in stage 3–4 CKD. In Cox regression analysis, a trend toward worse clinical outcomes existed when the HbA1c level exceeded 6% in stage 3–4 CKD, but the significance was only observed for >9%. The hazard ratios (HRs) for ESRD, all-cause mortality and combined CV events with mortality in the group of HbA1c >9% were 1.6 (95% CI, 1.07 to 2.38), 1.52 (95% CI, 0.97 to 2.38) and 1.46 (95% CI, 1.02 to 2.09), respectively. This study demonstrates that the higher HbA1c level is associated higher risks for clinical outcomes in diabetic patients with stage 3–4 CKD but not in stage 5 CKD. PMID:26818011

  11. Care at home of the patient with advanced multiple sclerosis--part 2.

    PubMed

    Reitman, Nancy Clayton

    2010-05-01

    Clinicians caring for patients with advanced MS have choices of different options and approaches. Whatever path is chosen, interventions must incorporate the wishes and capabilities of the patient and be supported by the care team, usually led by the nurse. As the work of the great psychologist Abraham Maslow has shown, in his famous "hierarchy of needs," the basic levels of needs must be met before the highest self-actualization can be accomplished (Maslow, 1943). This is equally true in the nursing care of very ill patients, as authors Zalenski and Raspa write: "The five levels of the hierarchy of needs as adapted to palliative care are: (1) distressing symptoms, such as pain or dyspnea; (2) fears for physical safety, of dying or abandonment; (3) affection, love and acceptance in the face of devastating illness; (4) esteem, respect, and appreciation for the person; (5) self-actualization and transcendence. Maslow's modified hierarchy of palliative care needs could be utilized to provide a comprehensive approach for the assessment of patients' needs and the design of interventions to achieve goals that start with comfort and potentially extend to the experience of transcendence."(Zalenski & Raspa, 2006, p.1120).

  12. Multidisciplinary Service Utilization Pattern by Advanced Head and Neck Cancer Patients: A Single Institution Study

    PubMed Central

    Junn, Jacqueline C.; Kim, Irene A.; Zahurak, Marianna L.; Tan, Marietta; Fan, Katherine Y.; Lake, Spencer T.; Zaboli, David; Messing, Barbara P.; Ulmer, Karen; Harrer, Karen B.; Gold, Dorothy; Ryniak, Keri L.; Zinreich, Eva S.; Tang, Mei; Levine, Marshall A.; Blanco, Ray G.; Saunders, John R.; Califano, Joseph A.; Ha, Patrick K.

    2012-01-01

    Purpose. To analyze the patterns and associations of adjunctive service visits by head and neck cancer patients receiving primary, concurrent chemoradiation therapy. Methods. Retrospective chart review of patients receiving adjunctive support during a uniform chemoradiation regimen for stages III-IV head and neck squamous cell carcinoma. Univariate and multivariate models for each outcome were obtained from simple and multivariate linear regression analyses. Results. Fifty-two consecutive patients were assessed. Female gender, single marital status, and nonprivate insurance were factors associated with an increased number of social work visits. In a multivariate analysis, female gender and marital status were related to increased social work services. Female gender and stage IV disease were significant for increased nursing visits. In a multivariate analysis for nursing visits, living greater than 20 miles between home and hospital was a negative predictive factor. Conclusion. Treatment of advanced stage head and neck cancer with concurrent chemoradiation warrants a multidisciplinary approach. Female gender, single marital status, and stage IV disease were correlated with increased utilization of social work and nursing services. Distance over 20 miles from the center was a negative factor. This information may help guide the treatment team to allocate resources for the comprehensive care of patients. PMID:23118755

  13. Prognostic relevance of nutritional status in patients with advanced esophageal cancer.

    PubMed

    Bollschweiler, Elfriede; Herbold, Till; Plum, Patrick; Hölscher, Arnulf H

    2013-03-01

    Evaluation of: Clavier JB, Antoni D, Atlani D et al. Baseline nutritional status is prognostic factor after definitive radiochemotherapy for esophageal cancer. Dis. Esoph. doi:10.1111/j.1442-2050.2012.01441.x (2012) (Epub ahead of print). The influence of nutritional status of patients with esophageal cancer on the effect of chemoradiation is not well studied. In a retrospective study of 143 patients with definitive chemoradiation, the authors show that malnutrition is a negative prognostic factor. In the Western industrial world, the incidence of high BMI has greatly increased over the past few decades, together with the incidence of esophageal adenocarcinoma. Studies analyzing the influence of being overweight on the outcome after esophagectomy showed that a very high BMI has a negative impact on a patient's survival. The interpretation of results from prognostic studies will be more complicated if several therapeutic procedures are combined, for example, neoadjuvant or adjuvant therapies combining chemoradiation or chemotherapy and esophagectomy. Prospective randomized studies including the nutritional status and immune competence for patients with advanced cancer of the esophagus are necessary.

  14. Consensus statement on advancing research in emergency department operations and its impact on patient care.

    PubMed

    Yiadom, Maame Yaa A B; Ward, Michael J; Chang, Anna Marie; Pines, Jesse M; Jouriles, Nick; Yealy, Donald M

    2015-06-01

    The consensus conference on "Advancing Research in Emergency Department (ED) Operations and Its Impact on Patient Care," hosted by The ED Operations Study Group (EDOSG), convened to craft a framework for future investigations in this important but understudied area. The EDOSG is a research consortium dedicated to promoting evidence-based clinical practice in emergency medicine. The consensus process format was a modified version of the NIH Model for Consensus Conference Development. Recommendations provide an action plan for how to improve ED operations study design, create a facilitating research environment, identify data measures of value for process and outcomes research, and disseminate new knowledge in this area. Specifically, we call for eight key initiatives: 1) the development of universal measures for ED patient care processes; 2) attention to patient outcomes, in addition to process efficiency and best practice compliance; 3) the promotion of multisite clinical operations studies to create more generalizable knowledge; 4) encouraging the use of mixed methods to understand the social community and human behavior factors that influence ED operations; 5) the creation of robust ED operations research registries to drive stronger evidence-based research; 6) prioritizing key clinical questions with the input of patients, clinicians, medical leadership, emergency medicine organizations, payers, and other government stakeholders; 7) more consistently defining the functional components of the ED care system, including observation units, fast tracks, waiting rooms, laboratories, and radiology subunits; and 8) maximizing multidisciplinary knowledge dissemination via emergency medicine, public health, general medicine, operations research, and nontraditional publications.

  15. Learning the hard way! Setting up an RCT of aromatherapy massage for patients with advanced cancer.

    PubMed

    Westcombe, A M; Gambles, M A; Wilkinson, S M; Barnes, K; Fellowes, D; Maher, E J; Young, T; Love, S B; Lucey, R A; Cubbin, S; Ramirez, A J

    2003-06-01

    Aromatherapy massage is used in cancer palliative care to improve quality of life but there is little evidence for its effectiveness. A large pragmatic multicentre randomized controlled trial was set up to examine the effectiveness of aromatherapy in improving psychological distress and quality of life in patients with cancer. This paper examines the challenges encountered in the design and execution of the study. The original design, i) focused on palliative care patients with advanced disease; ii) had both a no-intervention and a treatment control group (relaxation therapy); and iii) adopted 90% power for sample size calculations. A varied measurement strategy was employed. Recruitment proved difficult, referrers were 'gate-keeping', patients were often too ill to approach and others declined. The trial was modified to ensure viability. Eligibility was extended to all patients with cancer irrespective of stage, the relaxation group was removed and the power reduced to 80%. Although it is not generally good practice to change a study design once recruitment has started, the changes were consistent with the original basic study aims and design principles. The data collection phase was successfully completed in July 2002. PMID:12822844

  16. Consensus statement on advancing research in emergency department operations and its impact on patient care.

    PubMed

    Yiadom, Maame Yaa A B; Ward, Michael J; Chang, Anna Marie; Pines, Jesse M; Jouriles, Nick; Yealy, Donald M

    2015-06-01

    The consensus conference on "Advancing Research in Emergency Department (ED) Operations and Its Impact on Patient Care," hosted by The ED Operations Study Group (EDOSG), convened to craft a framework for future investigations in this important but understudied area. The EDOSG is a research consortium dedicated to promoting evidence-based clinical practice in emergency medicine. The consensus process format was a modified version of the NIH Model for Consensus Conference Development. Recommendations provide an action plan for how to improve ED operations study design, create a facilitating research environment, identify data measures of value for process and outcomes research, and disseminate new knowledge in this area. Specifically, we call for eight key initiatives: 1) the development of universal measures for ED patient care processes; 2) attention to patient outcomes, in addition to process efficiency and best practice compliance; 3) the promotion of multisite clinical operations studies to create more generalizable knowledge; 4) encouraging the use of mixed methods to understand the social community and human behavior factors that influence ED operations; 5) the creation of robust ED operations research registries to drive stronger evidence-based research; 6) prioritizing key clinical questions with the input of patients, clinicians, medical leadership, emergency medicine organizations, payers, and other government stakeholders; 7) more consistently defining the functional components of the ED care system, including observation units, fast tracks, waiting rooms, laboratories, and radiology subunits; and 8) maximizing multidisciplinary knowledge dissemination via emergency medicine, public health, general medicine, operations research, and nontraditional publications. PMID:26014365

  17. The Attitudes of Chinese Cancer Patients and Family Caregivers toward Advance Directives

    PubMed Central

    Zhang, Qiu; Xie, Chuanbo; Xie, Shanghang; Liu, Qing

    2016-01-01

    Advance directives (ADs) have been legislated in many countries to protect patient autonomy regarding medical decisions at the end of life. China is facing a serious cancer burden and cancer patients’ quality at the end of life should be a concern. However, limited studies have been conducted locally to gather information about attitudes toward ADs. The purpose of this study was to investigate the attitudes of Chinese cancer patients and family caregivers toward ADs and to explore the predictors that are associated with attitudes. The study indicated that although there was low awareness of ADs, most cancer patients and family caregivers had positive attitudes toward ADs after related information was explained to them. Participants preferred to discuss ADs with medical staff when they were diagnosed with a life-threatening disease. Preferences for refusing life-sustaining treatment and choosing Hospice-Palliative Care (HPC) at the end of life would increase the likelihood of agreeing with ADs. This suggests that some effective interventions to help participants better understand end-of-life treatments are helpful in promoting ADs. Moreover, the development of HPC would contribute to Chinese cancer patients and family caregivers agreeing with ADs. PMID:27529264

  18. Approximation of Corrected Calcium Concentrations in Advanced Chronic Kidney Disease Patients with or without Dialysis Therapy

    PubMed Central

    Kaku, Yoshio; Ookawara, Susumu; Miyazawa, Haruhisa; Ito, Kiyonori; Ueda, Yuichiro; Hirai, Keiji; Hoshino, Taro; Mori, Honami; Yoshida, Izumi; Morishita, Yoshiyuki; Tabei, Kaoru

    2015-01-01

    Background The following calcium (Ca) correction formula (Payne) is conventionally used for serum Ca estimation: corrected total Ca (TCa) (mg/dl) = TCa (mg/dl) + [4 – albumin (g/dl)]; however, it is inapplicable to advanced chronic kidney disease (CKD) patients. Methods 1,922 samples in CKD G4 + G5 patients and 341 samples in CKD G5D patients were collected. Levels of TCa (mg/day), ionized Ca2+ (iCa2+) (mmol/l) and other clinical parameters were measured. We assumed the corrected TCa to be equal to eight times the iCa2+ value (measured corrected TCa). We subsequently performed stepwise multiple linear regression analysis using the clinical parameters. Results The following formula was devised from multiple linear regression analysis. For CKD G4 + G5 patients: approximated corrected TCa (mg/dl) = TCa + 0.25 × (4 – albumin) + 4 × (7.4 – pH) + 0.1 × (6 – P) + 0.22. For CKD G5D patients: approximated corrected TCa (mg/dl) = TCa + 0.25 × (4 – albumin) + 0.1 × (6 – P) + 0.05 × (24 – HCO3-) + 0.35. Receiver operating characteristic analysis showed the high values of the area under the curve of approximated corrected TCa for the detection of measured corrected TCa ≥8.4 mg/dl and ≤10.4 mg/dl for each CKD sample. Both intraclass correlation coefficients for each CKD sample demonstrated superior agreement using the new formula compared to the previously reported formulas. Conclusion Compared to other formulas, the approximated corrected TCa values calculated from the new formula for patients with CKD G4 + G5 and CKD G5D demonstrates superior agreement with the measured corrected TCa. PMID:26557841

  19. Critical appraisal of pazopanib as treatment for patients with advanced metastatic renal cell carcinoma.

    PubMed

    Bukowski, Ronald M

    2011-01-01

    The management of renal cell carcinoma (RCC) has undergone significant changes during the past 10 years, with the treatment of metastatic RCC undergoing the most radical changes. These developments reflect an enhanced understanding of this tumor's underlying biology, which was then translated into the development of a new treatment paradigm. Current therapeutic approaches for the management of patients with metastatic RCC utilize knowledge of histology, molecular abnormalities, clinical prognostic factors, the natural history of this malignancy, and the treatment efficacy and toxicity of available agents. The treatment options available for patients with metastatic RCC have changed dramatically over the past 6 years. Interferon-α and interleukin-2 were the previous mainstays of therapy, but since December 2005, six new agents have been approved in the US for the treatment of advanced RCC. Three are multi-targeted tyrosine kinase inhibitors (TKI) including sunitinib, sorafenib, and pazopanib, two target the mammalian target of rapamycin (temsirolimus and everolimus), and one is a humanized monoclonal antibody (bevacizumab in combination with interferon-α). The current review focuses on the newest TKI available to treat patients with metastatic RCC, pazopanib. The development of this agent both preclinically and clinically is reviewed. The efficacy and safety data from the pivotal clinical trials are discussed, and the potential role of pazopanib in the treatment of patients with metastatic RCC in comparison to other treatment alternatives is critically appraised. This agent has a favorable overall risk benefit, and the available data demonstrate efficacy in patients with metastatic RCC who are either treatment-naïve or cytokine refractory. It therefore represents another alternative for treatment of metastatic RCC patients.

  20. Aortic Counterpulsation Therapy in Patients with Advanced Heart Failure: Analysis of the TBRIDGE Registry

    PubMed Central

    Bezerra, Cristiano Guedes; Adam, Eduardo Leal; Baptista, Mariana Lins; Ciambelli, Giuliano Serafino; Bernoche, Liliane Kopel, Claudia; Lopes, Leonardo Nicolau Geisler Daud; Macatrão-Costa, Milena Frota; Falcão, Breno de Alencar Araripe; Lage, Silvia Gelas

    2016-01-01

    Background The use of aortic counterpulsation therapy in advanced heart failure is controversial. Objectives To evaluate the hemodynamic and metabolic effects of intra-aortic balloon pump (IABP) and its impact on 30-day mortality in patients with heart failure. Methods Historical prospective, unicentric study to evaluate all patients treated with IABP betwen August/2008 and July/2013, included in an institutional registry named TBRIDGE (The Brazilian Registry of Intra-aortic balloon pump in Decompensated heart failure - Global Evaluation). We analyzed changes in oxygen central venous saturation (ScvO2), arterial lactate, and use of vasoactive drugs at 48 hours after IABP insertion. The 30-day mortality was estimated by the Kaplan-Meier method and diferences in subgroups were evaluated by the Log-rank test. Results A total of 223 patients (mean age 49 ± 14 years) were included. Mean left ventricle ejection fraction was 24 ± 10%, and 30% of patients had Chagas disease. Compared with pre-IABP insertion, we observed an increase in ScvO2 (50.5% vs. 65.5%, p < 0.001) and use of nitroprusside (33.6% vs. 47.5%, p < 0.001), and a decrease in lactate levels (31.4 vs. 16.7 mg/dL, p < 0.001) and use of vasopressors (36.3% vs. 25.6%, p = 0.003) after IABP insertion. Thirty-day survival was 69%, with lower mortality in Chagas disease patients compared without the disease (p = 0.008). Conclusion After 48 hours of use, IABP promoted changes in the use of vasoactive drugs, improved tissue perfusion. Chagas etiology was associated with lower 30-day mortality. Aortic counterpulsation therapy is an effective method of circulatory support for patients waiting for heart transplantation. PMID:26690691

  1. Visualization of nigrosome 1 and its loss in PD

    PubMed Central

    Schwarz, Stefan T.; Pitiot, Alain; Stephenson, Mary C.; Lowe, James; Bajaj, Nin; Bowtell, Richard W.; Auer, Dorothee P.; Gowland, Penny A.

    2013-01-01

    Objective: This study assessed whether high-resolution 7 T MRI allowed direct in vivo visualization of nigrosomes, substructures of the substantia nigra pars compacta (SNpc) undergoing the greatest and earliest dopaminergic cell loss in Parkinson disease (PD), and whether any disease-specific changes could be detected in patients with PD. Methods: Postmortem (PM) midbrains, 2 from healthy controls (HCs) and 1 from a patient with PD, were scanned with high-resolution T2*-weighted MRI scans, sectioned, and stained for iron and neuromelanin (Perl), TH, and calbindin. To confirm the identification of nigrosomes in vivo on 7 T T2*-weighted scans, we assessed colocalization with neuromelanin-sensitive T1-weighted scans. We then assessed the ability to depict PD pathology on in vivo T2*-weighted scans by comparing data from 10 patients with PD and 8 age- and sex-matched HCs. Results: A hyperintense, ovoid area within the dorsolateral border of the otherwise hypointense SNpc was identified in the HC brains on in vivo and PM T2*-weighted MRI. Location, size, shape, and staining characteristics conform to nigrosome 1. Blinded assessment by 2 neuroradiologists showed consistent bilateral absence of this nigrosome feature in all 10 patients with PD, and bilateral presence in 7/8 HC. Conclusions: In vivo and PM MRI with histologic correlation demonstrates that high-resolution 7 T MRI can directly visualize nigrosome 1. The absence of nigrosome 1 in the SNpc on MRI scans might prove useful in developing a neuroimaging diagnostic test for PD. PMID:23843466

  2. “EXHALE”: exercise as a strategy for rehabilitation in advanced stage lung cancer patients: a randomized clinical trial comparing the effects of 12 weeks supervised exercise intervention versus usual care for advanced stage lung cancer patients

    PubMed Central

    2013-01-01

    Background Lung cancer is the leading cause of cancer death in North America and Western Europe. Patients with lung cancer in general have reduced physical capacity, functional capacity, poor quality of life and increased levels of anxiety and depression. Intervention studies indicate that physical training can address these issues. However, there is a lack of decisive evidence regarding the effect of physical exercise in patients with advanced lung cancer. The aim of this study is to evaluate the effects of a twelve weeks, twice weekly program consisting of: supervised, structured training in a group of advanced lung cancer patients (cardiovascular and strength training, relaxation). Methods/Design A randomized controlled trial will test the effects of the exercise intervention in 216 patients with advanced lung cancer (non-small cell lung cancer (NSCLC) stage IIIb - IV and small cell lung cancer (SCLC) extensive disease (ED)). Primary outcome is maximal oxygen uptake (VO2peak). Secondary outcomes are muscle strength (1RM), functional capacity (6MWD), lung capacity (Fev1) and patient reported outcome (including anxiety, depression (HADS) and quality of life (HRQOL)). Discussion The present randomized controlled study will provide data on the effectiveness of a supervised exercise intervention in patients receiving systemic therapy for advanced lung cancer. It is hoped that the intervention can improve physical capacity and functional level, during rehabilitation of cancer patients with complex symptom burden and help them to maintain independent function for as long as possible. Trial registration http://ClinicalTrials.gov, NCT01881906 PMID:24124893

  3. Safety and Tumor Responses with Lambrolizumab (Anti–PD-1) in Melanoma

    PubMed Central

    Hamid, Omid; Robert, Caroline; Daud, Adil; Hodi, F. Stephen; Hwu, Wen-Jen; Kefford, Richard; Wolchok, Jedd D.; Hersey, Peter; Joseph, Richard W.; Weber, Jeffrey S.; Dronca, Roxana; Gangadhar, Tara C.; Patnaik, Amita; Zarour, Hassane; Joshua, Anthony M.; Gergich, Kevin; Elassaiss-Schaap, Jeroen; Algazi, Alain; Mateus, Christine; Boasberg, Peter; Tumeh, Paul C.; Chmielowski, Bartosz; Ebbinghaus, Scot W.; Li, Xiaoyun Nicole; Kang, S. Peter; Ribas, Antoni

    2014-01-01

    BACKGROUND The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. We tested the anti–PD-1 antibody lambrolizumab (previously known as MK-3475) in patients with advanced melanoma. METHODS We administered lambrolizumab intravenously at a dose of 10 mg per kilogram of body weight every 2 or 3 weeks or 2 mg per kilogram every 3 weeks in patients with advanced melanoma, both those who had received prior treatment with the immune checkpoint inhibitor ipilimumab and those who had not. Tumor responses were assessed every 12 weeks. RESULTS A total of 135 patients with advanced melanoma were treated. Common adverse events attributed to treatment were fatigue, rash, pruritus, and diarrhea; most of the adverse events were low grade. The confirmed response rate across all dose cohorts, evaluated by central radiologic review according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, was 38% (95% confidence interval [CI], 25 to 44), with the highest confirmed response rate observed in the cohort that received 10 mg per kilogram every 2 weeks (52%; 95% CI, 38 to 66). The response rate did not differ significantly between patients who had received prior ipilimumab treatment and those who had not (confirmed response rate, 38% [95% CI, 23 to 55] and 37% [95% CI, 26 to 49], respectively). Responses were durable in the majority of patients (median follow-up, 11 months among patients who had a response); 81% of the patients who had a response (42 of 52) were still receiving treatment at the time of analysis in March 2013. The overall median progression-free survival among the 135 patients was longer than 7 months. CONCLUSIONS In patients with advanced melanoma, including those who had had disease progression while they had been receiving ipilimumab, treatment with lambrolizumab resulted in a high rate of sustained tumor regression, with mainly grade 1 or 2 toxic effects

  4. Advanced practice physiotherapy in patients with musculoskeletal disorders: a systematic review

    PubMed Central

    2012-01-01

    Background The convergence of rising health care costs and physician shortages have made health care transformation a priority in many countries resulting in the emergence of new models of care that often involve the extension of the scope of practice for allied health professionals. Physiotherapists in advanced practice/extended scope roles have emerged as key providers in such new models, especially in settings providing services to patients with musculoskeletal disorders. However, evidence of the systematic evaluation of advance physiotherapy practice (APP) models of care is scarce. A systematic review was done to update the evaluation of physiotherapists in APP roles in the management of patients with musculoskeletal disorders. Methods Structured literature search was conducted in 3 databases (Medline, Cinahl and Embase) for articles published between 1980 and 2011. Included studies needed to present original quantitative data that addressed the impact or the effect of APP care. A total of 16 studies met all inclusion criteria and were included. Pairs of raters used four structured quality appraisal methodological tools depending on design of studies to analyse included studies. Results Included studies varied in designs and objectives and could be categorized in four areas: diagnostic agreement or accuracy compared to medical providers, treatment effectiveness, economic efficiency or patient satisfaction. There was a wide range in the quality of studies (from 25% to 93%), with only 43% of papers reaching or exceeding a score of 70% on the methodological quality rating scales. Their findings are however consistent and suggest that APP care may be as (or more) beneficial than usual care by physicians for patients with musculoskeletal disorders, in terms of diagnostic accuracy, treatment effectiveness, use of healthcare resources, economic costs and patient satisfaction. Conclusions The emerging evidence suggests that physiotherapists in APP roles provide equal

  5. Endogenous tumor-reactive CD8+ T cells are differentiated effector cells expressing high levels of CD11a and PD-1 but are unable to control tumor growth

    PubMed Central

    Liu, Xin; Gibbons, Rachel M; Harrington, Susan M; Krco, Christopher J; Markovic, Svetomir N; Kwon, Eugene D; Dong, Haidong

    2013-01-01

    Immunotherapies aimed at enhancing natural or endogenous antitumor T-cell immunity in patients affected by advanced malignancies are currently being implemented in the clinic with promising results. In order to optimize therapeutic protocols and monitor the effectiveness of such therapies, reliable biomarkers are needed. We used CD11a, an integrin that is upregulated on the surface of effector and memory CD8+ T cells, and PD-1, an immunoregulatory receptor expressed by activated T cells, as biomarkers to identify, quantify and monitor endogenous tumor-reactive cytotoxic T lymphocytes (CTLs) in two mouse tumor models and in the peripheral blood of 12 patients affected by Stage IV melanoma. High expression levels of CD11a and PD-1 were detected among CD8+ T cells residing within primary and metastatic murine tumor sites, as well as in spontaneous murine breast cancer tissues. In the peripheral blood of melanoma patients, tumor antigen-specific CD8+ T cells were associated with a population of CD11ahigh CD8+ T cells that co-expressed high levels of PD-1. Healthy donors exhibited a comparatively much lower frequency of such PD-1+CD11ahighCD8+ T cells. Phenotypic analyses demonstrated that CD11ahighCD8+ T cells are proliferating (Ki67+) and activated (CD62L-CD69+). Increased CD11ahighCD8+ T cells and delayed tumor growth were observed in PD-1 deficient mice, suggesting that the antitumor effector functions of CD8+ T cells is compromised by an elevated expression of PD-1. The CD11ahighCD8+ T-cell population expresses high levels of PD-1 and presumably constitutes the cellular target of PD-1 blockade therapy. The expression level of CD11a and PD-1 by CD8+ T cells may therefore represent a novel biomarker to identify and monitor endogenous tumor-reactive CTLs. This may not only provide an immunological readout for evaluating the efficacy of immunotherapy but also contribute to the selection of cancer patients who are likely to benefit from anti-PD-1 therapy. PMID:23894697

  6. Sarcomatoid lung carcinomas show high levels of Programmed death Ligand-1 (PD-L1)

    PubMed Central

    Velcheti, Vamsidhar; Rimm, David L.; Schalper, Kurt A.

    2013-01-01

    Programmed death-1 (PD-1) is a co-inhibitory inducible receptor present on T-cells and macrophages. Tumor cells with increased programmed death ligand-1 (PD-L1) are believed to escape immunity through activation of PD-1/PD-L1 pathway and suppression of effector immune responses. Recent strategies targeting the PD-1/PD-L1 axis have shown promising results in patients with several tumors types, including lung carcinomas. Preliminary data suggests that PD-L1 protein expression might predictive response to such therapies. Sarcomatoid carcinomas (SCs) of the lung include rare subtypes of poorly differentiated non-small cell lung carcinomas (NSCLC) of high grade and aggressive behavior. The biology of these neoplasms is poorly understood and they frequently show increased local inflammatory and lymphocytic infiltration. Here, we report the expression of PD-L1 in 13 SCs from two large retrospective lung cancer cohorts. Using automated quantitative immunofloresence (aqIF/AQUA®) and a mouse monoclonal antibody directed against the extra-cellular domain of PD-L1, we show that 9 of 13 (69.2%) patients with SCs are positive for PD-L1 and their levels are higher than in conventional NSCLC. These results provide rationale for the potential use of targeted immunetherapy in lung SCs. PMID:23676558

  7. 18F-FDG PET/CT Reveals Disease Remission in a Patient With Ipilimumab-Refractory Advanced Melanoma Treated With Pembrolizumab.

    PubMed

    Sachpekidis, Christos; Hassel, Jessica C; Dimitrakopoulou-Strauss, Antonia

    2016-02-01

    Pembrolizumab is an anti-programmed cell death receptor 1 (anti-PD-1) antibody, recently approved for the treatment of ipilimumab-refractory metastatic melanoma. We report on a 49-year-old patient with unresectable metastatic melanoma initially treated with 4 cycles of ipilimumab. Because of demonstration of progressive disease on PET/CT, the patient was enrolled into a clinical trial of pembrolizumab. After completion of 4 cycles of pembrolizumab, the follow-up PET/CT scans performed early after and 7 months after the end of treatment exhibited complete disease remission, reflecting the potential role of the modality in treatment response evaluation of melanoma patients receiving anti-PD-1 therapy.

  8. CEA and CA19.9 as early predictors of progression in advanced/metastatic colorectal cancer patients receiving oxaliplatin-based chemotherapy and bevacizumab.

    PubMed

    Petrioli, Roberto; Licchetta, Antonella; Roviello, Giandomenico; Pascucci, Alessandra; Francini, Edoardo; Bargagli, Gianluca; Conca, Raffaele; Miano, Salvatora Tindara; Marzocca, Giuseppe; Francini, Guido

    2012-01-01

    We evaluated the changes of the tumor markers CEA and CA19.9 as early predictors of progression in metastatic colorectal cancer (mCRC) patients participating in a clinical study and receiving chemotherapy and bevacizumab (Bev). Seventy-two patients had high baseline CEA or CA19.9 serum levels. By ROC analyses, the areas under the curves were 0.83 for variable CEA cutoff values for distinguishing progressive disease (PD) versus stable disease (SD)/partial remission (PR)/complete remission (CR), and 0.80 for variable CA19.9 cutoff values for distinguishing PD versus SD/PR/CR. Rises in CEA and CA19.9 may early signal the occurrence of progression in mCRC patients receiving chemotherapy and Bev. PMID:22236191

  9. Constitution and thermodynamics of the Mo-Ru, Mo-Pd, Ru-Pd and Mo-Ru-Pd systems

    NASA Astrophysics Data System (ADS)

    Kleykamp, H.

    1989-09-01

    The constitution of the Mo-Ru, Mo-Pd and Ru-Pd systems was reinvestigated between 800 and 2000°C. The Mo-Ru system is of the eutectic type, a σ-phase Mo 5Ru 3 exists between 1915 and 1143°C. The Mo-Pd system is characterized by an hcp phase Mo 9Pd 11 and by two peritectic reactions, β- Mo( Pd) + L = Mo9Pd11andMo9Pd11 + L = α- Pd( Mo). Mo 9Pd 11 decomposes eutectoidally at 1370°C. The Ru-Pd system is simple peritectic. The continuous series of the hcp solid solutions between Mo 9Pd 11 and ɛ-Ru(Mo, Pd) in the ternary Mo-Ru-Pd system observed at 1700°C are suppressed below 1370°C near the Mo-Pd boundary system by the formation of a narrow α + β + ɛ three-phase field. Relative partial molar Gibbs energies of Mo, Mo and Ru in the respective binary systems and of Mo in the ternary system were measured by the EMF method with a Zr(Ca)O 2 electrolyte. xsΔ ḠMo∞ quantities were evaluated at 1200 K which give -43 kJ/mol Mo in Ru and -94 kJ/mol Mo in Pd at infinite dilution. Gibbs energies of formation of the Mo-Ru and Mo-Pd systems were calculated.

  10. Coping with Physical and Psychological Symptoms: A Qualitative Study of Advanced Lung Cancer Patients and their Family Caregivers

    PubMed Central

    Mosher, Catherine E.; Ott, Mary A.; Hanna, Nasser; Jalal, Shadia I.; Champion, Victoria L.

    2014-01-01

    Purpose Advanced lung cancer patients have high rates of multiple physical and psychological symptoms, and many of their family caregivers experience significant distress. However, little is known about strategies that these patients and their family caregivers employ to cope with physical and psychological symptoms. This study aimed to identify strategies for coping with various physical and psychological symptoms among advanced, symptomatic lung cancer patients and their primary family caregivers. Methods Patients identified their primary family caregiver. Individual semi-structured qualitative interviews were conducted with 21 advanced, symptomatic lung cancer patients and primary family caregivers. Thematic analysis of interview data was framed by stress and coping theory. Results Patients and caregivers reported maintaining a normal routine and turning to family and friends for support with symptom management, which often varied in its effectiveness. Whereas support from healthcare professionals and complementary and alternative medicine were viewed favorably, reactions to Internet and in-person support groups were mixed due to the tragic nature of participants’ stories. Several cognitive coping strategies were frequently reported (i.e., changing expectations, maintaining positivity, and avoiding illness-related thoughts) as well as religious coping strategies. Conclusions Results suggest that advanced lung cancer patients and caregivers may be more receptive to cognitive and religious approaches to symptom management and less receptive to peer support. Interventions should address the perceived effectiveness of support from family and friends. PMID:25527242

  11. Efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung squamous cell carcinoma

    PubMed Central

    Pi, Guoliang; He, Hanping; Bi, Jianping; Li, Ying; Li, Yanping; Zhang, Yong; Wang, Mingwei; Han, Guang; Lin, Chi

    2016-01-01

    Abstract Introduction: Currently, the options are limited for the treatment of patients who have failed 2 lines of chemotherapy for advanced lung squamous cell carcinoma (SCC). Recently, nivolumab, a fully human IgG4 programmed death 1 immune checkpoint inhibitor antibody, was approved to treat patients with advanced stage, relapsed/refractory lung SCC. Although nivolumab has demonstrated antitumor activity with survival benefit in Caucasian patients, its efficacy in Asian patients is unknown. Case Report: In this report, we describe a Chinese patient with relapsed advanced stage lung SCC who had an excellent response to nivolumab after only 2 doses without any adverse effects. Immunohistochemical analysis indicated the tumor was stained positive for programmed death-ligand 1. Conclusion: To our knowledge, this is the first report of satisfactory efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung SCC. Further clinical trials in Asian countries are needed to test whether nivolumab immunotherapy is a safe and effective treatment for Asian patients with lung SCC. PMID:27749580

  12. Radiotherapy and Hyperthermia for Treatment of Primary Locally Advanced Cervix Cancer: Results in 378 Patients

    SciTech Connect

    Franckena, Martine Lutgens, Ludy C.; Koper, Peter C.; Kleynen, Catharina E.; Steen-Banasik, Elsbieta M. van der; Jobsen, Jan J.; Leer, Jan Willem; Creutzberg, Carien L.; Dielwart, Michel F.; Norden, Yvette van; Canters, Richard A.M.; Rhoon, Gerard C. van; Zee, Jacoba van der

    2009-01-01

    Purpose: To report response rate, pelvic tumor control, survival, and late toxicity after treatment with combined radiotherapy and hyperthermia (RHT) for patients with locally advanced cervical carcinoma (LACC) and compare the results with other published series. Methods and Materials: From 1996 to 2005, a total of 378 patients with LACC (International Federation of Gynecology and Obstetrics Stage IB2-IVA) were treated with RHT. External beam radiotherapy (RT) was applied to 46-50.4 Gy and combined with brachytherapy. The hyperthermia (HT) was prescribed once weekly. Primary end points were complete response (CR) and local control. Secondary end points were overall survival, disease-specific survival, and late toxicity. Patient, tumor, and treatment characteristics predictive for the end points were identified in univariate and multivariate analyses. Results: Overall, a CR was achieved in 77% of patients. At 5 years, local control, disease-specific survival, and incidence of late toxicity Common Terminology Criteria for Adverse Events Grade 3 or higher were 53%, 47%, and 12%, respectively. In multivariate analysis, number of HT treatments emerged as a predictor of outcome in addition to commonly identified prognostic factors. Conclusions: The CR, local control, and survival rates are similar to previously observed results of RHT in the randomized Dutch Deep Hyperthermia Trial. Reported treatment results for currently applied combined treatment modalities (i.e., RT with chemotherapy and/or HT) do not permit definite conclusions about which combination is superior. The present results confirm previously shown beneficial effects from adding HT to RT and justify the application of RHT as first-line treatment in patients with LACC as an alternative to chemoradiation.

  13. Evaluation of Spiritual Needs of Patients with Advanced Cancer in a Palliative Care Unit

    PubMed Central

    Valls, Joan; Porta, Josep; Viñas, Juan

    2014-01-01

    Abstract Introduction: Spiritual needs play an important role in palliative care as both a clinical dimension and a therapeutic strategy. However, recent studies have shown that the management of this dimension still remains a challenge at the clinical level of palliative care. Goals: Our goal was to evaluate the spiritual needs of patients diagnosed with advanced and terminal cancer by the palliative care unit of a hospital in Barcelona, Spain. Methods: An observational study was conducted that involved 50 patients who were recruited between May 2007 and January 2008. A questionnaire was used which included 28 items selected from a review of the literature; the responses were analyzed using a five-point Lickert scale. The results were grouped in 11 categories corresponding to different spiritual needs. Results: Two spiritual needs emerged as the most relevant for the patients: their need to be recognized as a person until the end of their life and their need to know the truth about their illness. The least important spiritual needs were identified as those: for continuity and an afterlife; to get rid of obsessions; to achieve freedom from blame and to be able to forgive others; and the need for reconciliation and to feel forgiven by others. Conclusions: When patients knew the truth about their illnesses and they were treated with dignity, their most important needs were likely to be covered. These results suggest that patients receiving palliative care wish to live for the present with as much normality as possible and show only minor concern for their past and future. PMID:24745870

  14. Limited genomic heterogeneity of circulating melanoma cells in advanced stage patients

    NASA Astrophysics Data S