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Sample records for achieve long-term survival

  1. [A patient with invasive carcinoma derived from IPMN who achieved long-term survival despite lymph node metastasis].

    PubMed

    Ueda, Nobuhiko; Kaida, Daisuke; Tomita, Yasuto; Ohnishi, Toshio; Funaki, Hiroshi; Fujita, Hideto; Kinami, Shinichi; Nakano, Yasuharu; Kosaka, Takeo

    2014-11-01

    A woman in her 70s was referred for examination of liver dysfunction. A cystic lesion with irregular contrast was observed at the pancreas head. The bile and pancreatic ducts were obstructed by the lesion. Part of the branch of the pancreatic duct at the pancreas head, continuous with the main pancreatic duct, was observed to be extended by using pancreatography. Pancreaticoduodenectomy was performed, and a diagnosis of invasive carcinoma from an intraductal papillary-mucinous neoplasm (IPMN) was made. Postoperative pathological diagnosis showed 16b1 inter-node metastasis. Liver and lung metastases were also detected after surgery; nevertheless, long-term survival was achieved for 5 years and 2 months by using various treatment modalities.

  2. Induced neural stem cells achieve long-term survival and functional integration in the adult mouse brain.

    PubMed

    Hemmer, Kathrin; Zhang, Mingyue; van Wüllen, Thea; Sakalem, Marna; Tapia, Natalia; Baumuratov, Aidos; Kaltschmidt, Christian; Kaltschmidt, Barbara; Schöler, Hans R; Zhang, Weiqi; Schwamborn, Jens C

    2014-09-09

    Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

  3. Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment.

    PubMed

    Zugmaier, Gerhard; Gökbuget, Nicola; Klinger, Matthias; Viardot, Andreas; Stelljes, Matthias; Neumann, Svenja; Horst, Heinz-A; Marks, Reinhard; Faul, Christoph; Diedrich, Helmut; Reichle, Albrecht; Brüggemann, Monika; Holland, Chris; Schmidt, Margit; Einsele, Hermann; Bargou, Ralf C; Topp, Max S

    2015-12-10

    This long-term follow-up analysis evaluated overall survival (OS) and relapse-free survival (RFS) in a phase 2 study of the bispecific T-cell engager antibody construct blinatumomab in 36 adults with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). In the primary analysis, 25 (69%) patients with relapsed/refractory ALL achieved complete remission with full (CR) or partial (CRh) hematologic recovery of peripheral blood counts within the first 2 cycles. Twenty-five patients (69%) had a minimal residual disease (MRD) response (<10(-4) blasts), including 22 CR/CRh responders, 2 patients with hypocellular bone marrow, and 1 patient with normocellular bone marrow but low peripheral counts. Ten of the 36 patients (28%) were long-term survivors (OS ≥30 months). Median OS was 13.0 months (median follow-up, 32.6 months). MRD response was associated with significantly longer OS (Mantel-Byar P = .009). All 10 long-term survivors had an MRD response. Median RFS was 8.8 months (median follow-up, 28.9 months). A plateau for RFS was reached after ∼18 months. Six of the 10 long-term survivors remained relapse-free, including 4 who received allogeneic stem cell transplantation (allo-SCT) as consolidation for blinatumomab and 2 who received 3 additional cycles of blinatumomab instead of allo-SCT. Three long-term survivors had neurologic events or cytokine release syndrome, resulting in temporary blinatumomab discontinuation; all restarted blinatumomab successfully. Long-term survivors had more pronounced T-cell expansion than patients with OS <30 months.

  4. Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment

    PubMed Central

    Gökbuget, Nicola; Klinger, Matthias; Viardot, Andreas; Stelljes, Matthias; Neumann, Svenja; Horst, Heinz-A.; Marks, Reinhard; Faul, Christoph; Diedrich, Helmut; Reichle, Albrecht; Brüggemann, Monika; Holland, Chris; Schmidt, Margit; Einsele, Hermann; Bargou, Ralf C.; Topp, Max S.

    2015-01-01

    This long-term follow-up analysis evaluated overall survival (OS) and relapse-free survival (RFS) in a phase 2 study of the bispecific T-cell engager antibody construct blinatumomab in 36 adults with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). In the primary analysis, 25 (69%) patients with relapsed/refractory ALL achieved complete remission with full (CR) or partial (CRh) hematologic recovery of peripheral blood counts within the first 2 cycles. Twenty-five patients (69%) had a minimal residual disease (MRD) response (<10−4 blasts), including 22 CR/CRh responders, 2 patients with hypocellular bone marrow, and 1 patient with normocellular bone marrow but low peripheral counts. Ten of the 36 patients (28%) were long-term survivors (OS ≥30 months). Median OS was 13.0 months (median follow-up, 32.6 months). MRD response was associated with significantly longer OS (Mantel-Byar P = .009). All 10 long-term survivors had an MRD response. Median RFS was 8.8 months (median follow-up, 28.9 months). A plateau for RFS was reached after ∼18 months. Six of the 10 long-term survivors remained relapse-free, including 4 who received allogeneic stem cell transplantation (allo-SCT) as consolidation for blinatumomab and 2 who received 3 additional cycles of blinatumomab instead of allo-SCT. Three long-term survivors had neurologic events or cytokine release syndrome, resulting in temporary blinatumomab discontinuation; all restarted blinatumomab successfully. Long-term survivors had more pronounced T-cell expansion than patients with OS <30 months. PMID:26480933

  5. Long-term survival in Patau syndrome.

    PubMed

    Tunca, Y; Kadandale, J S; Pivnick, E K

    2001-04-01

    A female patient with an extra chromosome 13 (Patau syndrome) is described. There are only five previous reports of patients with trisomy 13 who have survived past the first decade. It is concluded that non-lethal congenital anomalies and aggressive medical care play an important role in the survival of patients with trisomy 13.

  6. Long-term survival in multiple myeloma

    PubMed Central

    João, Cristina; Costa, Carlos; Coelho, Inês; Vergueiro, Maria João; Ferreira, Mafalda; da Silva, Maria Gomes

    2014-01-01

    Key Clinical Message The survival of multiple myeloma patients has improved very significantly over the last decade. Still median overall survival is inferior to 5 years. A small proportion of patients survive longer than 10 years. In this paper we discuss four cases illustrating the nonhomogeneous clinical presentation and evolution of this subset of patients. Surprisingly, these long survivors do not always have deep responses and some require frequent treatments, which include autologous stem cell transplantation and novel drugs. The authors discuss several aspects of these clinical histories, including treatment options, raising hypothesis on their relation with long survivorship which may be important to have in consideration when studying this subject. PMID:25614805

  7. Long term Survival with CTLA-4 blockade Using Tremelimumab

    PubMed Central

    Eroglu, Zeynep; Kim, Dae Won; Wang, Xiaoyan; Camacho, Luis H.; Chmielowski, Bartosz; Seja, Elizabeth; Villanueva, Arturo; Ruchalski, Kathleen; Glaspy, John A.; Kim, Kevin B.; Hwu, Wen-Jen; Ribas, Antoni

    2016-01-01

    Purpose One of the hallmarks of cancer immunotherapy is the long duration of responses, evident with cytokines like interleukin-2 or a variety of cancer vaccines. However, there is limited information available on very long term outcomes of patients treated with anti-CTLA-4 antibodies. Tremelimumab is an anti-CTLA-4 antibody of Ig G2 istoype initially tested in patients with advanced melanoma over 12 years ago. Methods We reviewed the outcomes of patients with advanced melanoma enrolled in four phase 1 and 2 tremelimumab trials at two sites to determine response rates and long-term survival. Results A total of 143 patients were enrolled at two institutions from 2002 to 2008. Tremelimumab administration varied between a single dose of 0.01 mg/kg and 15 mg/kg every 3 months. Median overall survival was 13 months (95% CI, 10–16.6), ranging from less than a month to 12+ years. An objective response rate of 15.6% was observed, with median duration of response of 6.5 years, range of 3 to 136+ months. The Kaplan-Meier estimated 5 year survival rate was 20% (95% CI, 13–26%), with 10 and 12.5 year survival rates of 16% (95% CI, 9–23%). Conclusions CTLA-4 blockade with tremelimumab can lead to very long duration of objective anti-tumor responses beyond 12 years. PMID:26364516

  8. Metastatic lung cancer in the age of targeted therapy: improving long-term survival

    PubMed Central

    Del Rivero, Jaydira; Thomas, Anish

    2016-01-01

    Epidermal growth factor receptor (EGFR) mutations are the most frequent targetable genetic abnormality observed in non-small cell lung cancer (NSCLC). More than a decade after EGFR mutations were shown to predict sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKI), retrospective cohort studies are now identifying and characterizing 5-year survivors. While these studies indicate subsets of patients achieving long-term survival, there is paucity of data pertaining to the long-term survival benefits of these targeted therapies at a population level. Improving access to molecular testing and treatment are key to maximizing the survival benefits at a population level. PMID:28149768

  9. Long-term Survival after Metastatic Childhood Melanoma

    PubMed Central

    Jensen, Mette Bybjerg; Krag, Christen

    2014-01-01

    Summary: Malignant melanoma in children is very rare and accounts for only 1–3% of all melanomas. A congenital melanocytic nevus depending on the size of the lesion is one of the risk factors for developing childhood melanoma because of the possible malignant transformation. Childhood malignant melanoma is a potentially fatal disease. Surgical excision is the primary treatment of choice for malignant melanoma. Clinicians need to be aware of the possible malignant transformation in children with congenital melanocytic nevus because early diagnosis and treatment improves prognosis. The suspicion of malign melanoma must be in mind when evaluating a pigmented lesion in a pediatric patient. We present a case of a patient born with a congenital nevus diagnosed with metastatic childhood malignant scalp melanoma at the age of 6 years. The patient underwent surgical ablation and reconstruction and has survived 26 years without recurrence, thus representing an uplifting case of long-term survival of childhood melanoma. PMID:25289356

  10. Long term survival effect of metoprolol in dilated cardiomyopathy

    PubMed Central

    Di, L; De Maria, R; Gavazzi, A; Gregori, D; Parolini, M; Sinagra, G; Salvatore, L; Longaro, F; Bernobich, E; Camerini, F

    1998-01-01

    Objective—To evaluate the additive effect of metoprolol treatment on long term incidence of fatal and non-fatal cardiac events in idiopathic dilated cardiomyopathy.
Design—586 patients with idiopathic dilated cardiomyopathy were prospectively enrolled in a multicentre registry and followed up for a mean (SD) of 52 (32) months. Metoprolol, carefully titrated to the maximum tolerated dose, was added to conventional heart failure treatment in 175 patients.
Results—Survival and transplant-free survival at seven years were significantly higher in the 175 metoprolol treated patients than in the remaining 411 on standard treatment (81% v 60%, p < 0.001, and 69% v 49%, p < 0.001, respectively). By multivariate analysis, metoprolol independently predicted survival and transplant-free survival (relative risk reduction values for all cause mortality and combined mortality or transplantation 51% (95% confidence interval 21% to 69%), p = 0.002, and 34% (5% to 53%), p = 0.01, respectively). New York Heart Association class, left ventricular end diastolic diameter, and pulmonary wedge pressure were also predictive. Seven year survival (80% v 62%, p = 0.004) and transplant-free survival (68% v 51%, p = 0.005) were significantly higher in 127 metoprolol treated cases than in 127 controls selected from the entire control cohort and appropriately matched. Metoprolol was associated with a 30% reduction in all cause mortality (7% to 48%, p = 0.015) and a 26% reduction in mortality or transplantation (7% to 41%, p = 0.009). 
Conclusions—The addition of metoprolol to standard heart failure treatment, including angiotensin converting enzyme inhibitors, was effective in the long term, reducing both all cause mortality and transplantation in patients with idiopathic dilated cardiomyopathy.

 Keywords: β blockade;  dilated cardiomyopathy;  heart failure PMID:9616339

  11. Long-term survival after orthotopic and heterotopic cardiac transplantation.

    PubMed Central

    Cooper, D K; Charles, R G; Fraser, R C; Beck, W; Barnard, C N

    1980-01-01

    Five long-term survivors of heart transplantation were reinvestigated. Two patients had undergone orthotopic heart transplantation over 11 and 9 years earlier and constitute two of the world's longest-surviving patients after this procedure. Three patients had undergone heterotopic heart transplantation (one left heart bypass alone and two biventricular bypass) four to six years earlier. Four of the five patients had had only one or no documented acute rejection episodes. Three had been given blood transfusions. None had had particularly good tissue matching in relation to the donor on HLA typing. All five patients were leading full and active lives. At review two patients had significant coronary artery disease, one severe, presumably due to chronic immune-complex deposition. Heart transplantation remains a major undertaking, but it can offer the patient many years of good-quality life. Images p1095-a p1095-b PMID:7000291

  12. Long-term survival after chronic subdural haematoma.

    PubMed

    Manickam, Appukutty; Marshman, Laurence A G; Johnston, Ross

    2016-12-01

    Outcome after chronic subdural haematoma (CSDH) is invariably assumed favourable: however, little data regarding long term survival (LTS) exists. One study reported excess mortality restricted to year 1, but with expected actuarial rates thereafter. We aimed to determine LTS after CSDH in a retrospective analysis relative to actuarial data from age-matched controls. Data was obtained in n=155, (M:F 97:58, 69.3±2.3years). Follow-up maxima was 14.19years (mean: 4.02±3.07years, median: 5.2years). Mortality in-hospital, at 6months, 1year, 2years and 5years was n=13 (8.39%), n=22 (14.19%), n=31 (20.35%), n=42 (27.1%) and n=54 (34.84%). LTS was significantly worse than controls (5.29±0.59years vs. 17.74±1.8years, hazard ratio [HR]: 3.52, P<0.0001). Death most frequently related to pneumonia/sepsis and ischemic heart disease (IHD). Median modified Rankin score (mRS) in those discharged home (n=94, 60.65%) was 2 [IQR: 1-3]. Discharge mRS in those who died at 6months, 1year, 2years and 5years was 5 [IQR: 3-6], 5 [IQR: 4-6], 3 [IQR: 1-3], 4 [IQR: 2-5]. Discharge mRS was significantly worse with year 1 mortality (P=0.014). LTS related to discharge mRS (HR: 37.006, P<0.001), post-operative motor-score (HR: 0.581, P=0.0026), IHD (HR: 5.186, P=0.005), warfarin-use (HR: 5.93, P=0.036) and dementia (HR: 5.39, P=0.031). No long term recurrences (LTR) were recorded. Although most were discharged home with mRS=2, LTS was markedly less than previously reported: peers lived 12.4years longer. Although greater in year 1, excess mortality was not restricted to year 1, but continued throughout prolonged follow-up. LTS related to discharge disability and dependence, and co-morbid risk factors for cerebral atrophy. No LTR suggests that, once ultimately closed, the 'subdural space' remains closed. CSDH patients represent a vulnerable group who require continued long-term medical surveillance.

  13. Researchers seek clues to long-term survival.

    PubMed

    1995-04-01

    As many as 12 percent of HIV-infected homosexual men in the United States could remain AIDS-free for 20 years after seroconversion, and the median length of survival for children with AIDS may now be as high as eight years, according to several new studies presented at a national conference. At the Second National Conference on Human Retroviruses and Related Infections in Washington, D.C., researchers estimated that the percentage of long-term survivors in the United States is about 5-10 percent. Director of the National Institute of Allergy and Infectious Diseases, Anthony Fauci, MD, reported that immune system cells, also called CD8 cells, may be more efficient than antiretroviral therapy in repressing HIV infection, as reported in the January 26, 1995 issue of the New England Journal of Medicine. Interleukin-2, a natural protein that induces CD8 cells to suppress the virus, is showing promising preliminary results. Another study, published in the December 1994 issue of AIDS Research and Human Retroviruses, suggests that a women infected with the virus thirteen years ago through a blood transfusion but who has little trace of the virus in her blood, is able to suppress all HIV viruses that infected her and only defective, slow-growing viruses have remained within her white cells. Another study suggests that ongoing high-risk behavior might be associated with rapid progression and that people might be superinfected with more pathogenic virus.

  14. Motivation and Long-Term Language Achievement: Understanding Motivation to Persist in Foreign Language Learning

    ERIC Educational Resources Information Center

    Smith, Laura Jeanne

    2009-01-01

    Achieving native-like proficiency in a foreign language is a long-term process; therefore, designing and implementing a plan for long-term language achievement may help more learners achieve their long-term language goals of fluency as well as related career goals. This study presents recommendations that may be incorporated into the college…

  15. Breast malignant phyllodes tumor with rare pelvic metastases and long-term overall survival

    PubMed Central

    Shan, Jinlan; Zhang, Shizhen; Wang, Zhen; Fu, Yanbiao; Li, Ling; Wang, Xiaochen

    2016-01-01

    Abstract Background: Malignant phyllodes tumor (PT) is a rare fibro epithelial neoplasm of the breast, which is poor prognosis due to high risk of recurrence and distant metastasis. Methods: We report a case of malignant PT. It had recurred locally five times, and the sixth relapse was occurred 54 months after first diagnosis, presenting a huge pelvic mass (14 cm × 11 cm) by CT scan. Histopathological examination has demonstrated a metastatic phyllodes tumor. After postoperative chemotherapy treatment, a longer survival has been achieved, which is more than 72 months. Results: Our case report describes a breast PT with several local recurrences and a rare metastasis (pelvic cavity), but long-term overall survival was achieved after surgery and chemotherapy. Conclusion: We conclude that trustworthy prognosticators that identify patients with excessive potential of aggressive clinical course should be explored. Moreover, proper treatment could prolong overall survival of metastatic PT patients. PMID:27661051

  16. Prolymphocytic leukemia: postmortem findings after long-term survival.

    PubMed

    Pacheco, J; Hillman, N; Lin, J; Batata, A

    1983-07-01

    A patient had prolymphocytic leukemia and survived for 44 months. A partial remission for more than 11 months and a short complete remission were induced by agents commonly used for the treatment of acute myelocytic leukemia. However, surface markers identified the disease as of B-cell origin.

  17. Pancreatic carcinosarcoma with rare long-term survival

    PubMed Central

    Jia, Zhe; Zhang, Ke; Huang, RongHai; Zhou, XinGang; Jiang, Li

    2017-01-01

    Abstract Patient concerns: We report a rare case of pancreatic carcinosarcoma involving a 44-year-old woman. The patient complained of discomfort associated with the upper abdomen and jaundice of skin and sclera for 1 week. Diagnoses: After hospitalization, relevant examinations were completed. The disease was diagnosed as carcinoma of the pancreatic head. Interventions: Whipple procedure was conducted in May 2013. Intraoperative exploration indicated 2 components of the tumor: a fish-shaped gray matter and a hard structure similar to cancellous bone. Histopathological examination showed adenocarcinoma and osteosarcoma. After surgery, the patient received 8 cycles of chemotherapy with gemcitabine and raltitrexed. Outcomes: Previous studies indicated poor prognosis for pancreatic carcinosarcoma. However, our patient survived for 31 months with no recurrence till date. Lessons subsections: Coexistence of pancreatic adenocarcinoma and osteosarcoma is very rare. Our case was also an exception in manifesting longer survival than expected. PMID:28121946

  18. Long-term survival of bacterial spores in space

    NASA Technical Reports Server (NTRS)

    Horneck, G.; Bucker, H.; Reitz, G.

    1994-01-01

    On board of the NASA Long Duration Exposure Facility (LDEF), spores of Bacillus subtilis in monolayers (10(exp 6)/sample) or multilayers (10(exp 8)/sample) were exposed to the space environment for nearly six years and their survival was analyzed after retrieval. The response to space parameters, such as vacuum (10(exp -6) Pa), solar electromagnetic radiation up to the highly energetic vacuum-ultraviolet range 10(exp 9) J/sq m) and/or cosmic radiation (4.8 Gy), was studied and compared to the results of a simultaneously running ground control experiment. If shielded against solar ultraviolet (UV)-radiation, up to 80% of spores in multilayers survive in space. Solar UV-radiation, being the most deleterious parameter of space, reduces survival by 4 orders of magnitude or more. However, up to 10(exp 4) viable spores were still recovered, even in completely unprotected samples. Substances, such as glucose or buffer salts serve as chemical protectants. With this 6 year study in space, experimental data are provided to the discussion on the likelihood of 'Panspermia'.

  19. Long-term survival of bacterial spores in space.

    PubMed

    Horneck, G; Bucker, H; Reitz, G

    1994-10-01

    On board of the NASA Long Duration Exposure Facility (LDEF), spores of Bacillus subtilis in monolayers (10(6)/sample) or multilayers (10(8)/sample) were exposed to the space environment for nearly six years and their survival was analyzed after retrieval. The response to space parameters, such as vacuum (10(-6) Pa), solar electromagnetic radiation up to the highly energetic vacuum-ultraviolet range (10(9) J/m2) and/or cosmic radiation (4.8 Gy), was studied and compared to the results of a simultaneously running ground control experiment. If shielded against solar ultraviolet (UV)-radiation, up to 80 % of spores in multilayers survive in space. Solar UV-radiation, being the most deleterious parameter of space, reduces survival by 4 orders of magnitude or more. However, up to 10(4) viable spores were still recovered, even in completely unprotected samples. Substances, such as glucose or buffer salts serve as chemical protectants. With this 6 year study in space, experimental data are provided to the discussion on the likelihood of "Panspermia".

  20. Long-term survival after chest-wall reconstruction with musculocutaneous flaps

    SciTech Connect

    Kroll, S.S.; Schusterman, M.A.; Larson, D.L.; Fender, A. )

    1990-10-01

    Reconstruction of chest-wall defects with musculocutaneous flaps permits resection of advanced chest-wall tumors and of tissues severely damaged by radiotherapy in patients who in a previous era were not surgically treatable. To determine the long-term outcome from this surgery, the records of 96 patients who had undergone chest-wall resection with musculocutaneous flap reconstruction were reviewed. Median survival for the entire group was 20.5 months, but a more accurate prediction of outcome could be obtained by dividing the patients into three groups. In group I, patients free of known malignancy and undergoing resection of radionecrotic tissues, median survival was 60.0 months. In group II, patients with resectable disease and free of tumor following surgery, median survival was 31.1 months. In group III, patients incompletely resected or known to have metastatic disease following surgery, median survival was only 12.5 months. Even in group III, however, some individuals achieved prolonged survival and lasting benefits from the surgery, so these data should not be used to exclude patients from undergoing necessary palliative procedures.

  1. Alcohol liver disease: A review of current therapeutic approaches to achieve long-term abstinence

    PubMed Central

    García, María Luisa Gutiérrez; Blasco-Algora, Sara; Fernández-Rodríguez, Conrado M

    2015-01-01

    Harmful alcohol drinking may lead to significant damage on any organ or system of the body. Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease in Europe. In ALD, only alcohol abstinence was associated with a better long-term survival. Therefore, current effective therapeutic strategy should be oriented towards achieving alcohol abstinence or a significant reduction in alcohol consumption. Screening all primary care patients to detect those cases with alcohol abuse has been proposed as population-wide preventive intervention in primary care. It has been suggested that in patients with mild alcohol use disorder the best approach is brief intervention in the primary care setting with the ultimate goal being abstinence, whereas patients with moderate-to-severe alcohol use disorder must be referred to specialized care where detoxification and medical treatment of alcohol dependence must be undertaken. PMID:26229395

  2. Treatment of diabetes and long-term survival after insulin and glucokinase gene therapy.

    PubMed

    Callejas, David; Mann, Christopher J; Ayuso, Eduard; Lage, Ricardo; Grifoll, Iris; Roca, Carles; Andaluz, Anna; Ruiz-de Gopegui, Rafael; Montané, Joel; Muñoz, Sergio; Ferre, Tura; Haurigot, Virginia; Zhou, Shangzhen; Ruberte, Jesús; Mingozzi, Federico; High, Katherine A; Garcia, Felix; Bosch, Fatima

    2013-05-01

    Diabetes is associated with severe secondary complications, largely caused by poor glycemic control. Treatment with exogenous insulin fails to prevent these complications completely, leading to significant morbidity and mortality. We previously demonstrated that it is possible to generate a "glucose sensor" in skeletal muscle through coexpression of glucokinase and insulin, increasing glucose uptake and correcting hyperglycemia in diabetic mice. Here, we demonstrate long-term efficacy of this approach in a large animal model of diabetes. A one-time intramuscular administration of adeno-associated viral vectors of serotype 1 encoding for glucokinase and insulin in diabetic dogs resulted in normalization of fasting glycemia, accelerated disposal of glucose after oral challenge, and no episodes of hypoglycemia during exercise for >4 years after gene transfer. This was associated with recovery of body weight, reduced glycosylated plasma proteins levels, and long-term survival without secondary complications. Conversely, exogenous insulin or gene transfer for insulin or glucokinase alone failed to achieve complete correction of diabetes, indicating that the synergistic action of insulin and glucokinase is needed for full therapeutic effect. This study provides the first proof-of-concept in a large animal model for a gene transfer approach to treat diabetes.

  3. Long-term survival with diaphanospondylodysostosis (DSD): survival to 5 years and further phenotypic characteristics.

    PubMed

    Scottoline, Brian; Rosenthal, Scott; Keisari, Rami; Kirpekar, Rashmi; Angell, Cathy; Wallerstein, Robert

    2012-06-01

    We report on the natural history of diaphanospondylodysostosis (DSD) in the longest known survivor. DSD is a rare form of autosomal recessive vertebral dysotosis recently identified to be caused by a mutation in the BMPER gene. This condition is characterized by absent or severely delayed ossification of vertebral bodies, short broad thorax, short neck, protuberant abdomen, marked respiratory insufficiency, and normal appendicular skeleton. It is one of a number of spinal dysostoses, which are a heterogeneous group of axial skeletal malformations occurring during blastogenesis with continued evolution after birth. Significant medical intervention and at-home support contributed to the long-term survival of our patient. The patient had tracheomalacia, which resulted in respiratory insufficiency with thoracic insufficiency syndrome (TIS). Tracheostomy and vertical expandable prosthetic titanium rib (VEPTR) insertion operations ameliorated his symptoms. In addition, comprehensive physical and occupational therapy was performed due to chronic hypotonia. A consistent feature of all described DSD cases thus far are renal findings of dysplasia, nephrogenic rests or nephroblastomatosis, and/or cysts. The patient's renal cysts were monitored with serial ultrasounds at approximately 6-month intervals. The patient was diagnosed with bilateral renal cysts by ultrasound as a neonate, with eventual diagnosis at approximately 20 months of age with nephroblastoma suggesting this maybe an intrinsic part of DSD. The lack of other cases with nephroblastoma is likely related to the previously reported short period of survival.

  4. Long-term survival of a cow with cervical ectopia cordis.

    PubMed

    Onda, Ken; Sugiyama, Masanori; Niho, Keeko; Sato, Reiichiro; Arai, Sachiko; Kaneko, Kazuyuki; Ito, Seigo; Muto, Makoto; Suganuma, Tsunenori; Wakao, Yoshito; Wada, Yasunori

    2011-06-01

    This study investigated the long-term survival of a calf with cervical ectopia cordis that grew normally, became pregnant, and calved normally. The cow showed normal cardiac function and absence of peripheral circulation abnormalities. This paper documents antemortem characteristics of the affected cow.

  5. Long-term survival of a cow with cervical ectopia cordis

    PubMed Central

    Onda, Ken; Sugiyama, Masanori; Niho, Keeko; Sato, Reiichiro; Arai, Sachiko; Kaneko, Kazuyuki; Ito, Seigo; Muto, Makoto; Suganuma, Tsunenori; Wakao, Yoshito; Wada, Yasunori

    2011-01-01

    This study investigated the long-term survival of a calf with cervical ectopia cordis that grew normally, became pregnant, and calved normally. The cow showed normal cardiac function and absence of peripheral circulation abnormalities. This paper documents antemortem characteristics of the affected cow. PMID:22131586

  6. Diabetes and cardiovascular disease: changing the focus from glycemic control to improving long-term survival.

    PubMed

    Wang, Cecilia C Low; Reusch, Jane E B

    2012-11-06

    Diabetes mellitus (DM) is the fifth-leading cause of death worldwide and contributes to leading causes of death, cancer and cardiovascular disease, including CAD, stroke, peripheral vascular disease, and other vascular disease. While glycemic management remains a cornerstone of DM care, the co-management of hypertension, atherosclerosis, cardiovascular risk reduction, and prevention of long-term consequences associated with DM are now well recognized as essential to improve long-term survival. Clinical trial evidence substantiates the importance of glycemic control, low-density cholesterol-lowering therapy, blood pressure lowering, control of albuminuria, and comprehensive approaches targeting multiple risk factors to reduce cardiovascular risk. This article presents a review of the role of DM in the pathogenesis of atherosclerosis and cardiac dysfunction, recent evidence on the degree of glycemic control and mortality, and available evidence for a multifaceted approach to improve long-term outcomes for patients.

  7. Long-term survival following in-hospital cardiac arrest: A matched cohort study☆

    PubMed Central

    Feingold, Paul; Mina, Michael J.; Burke, Rachel M.; Hashimoto, Barry; Gregg, Sara; Martin, Greg S.; Leeper, Kenneth; Buchman, Timothy

    2016-01-01

    Background Each year, 200,000 patients undergo an in-hospital cardiac arrest (IHCA), with approximately 15–20% surviving to discharge. Little is known, however, about the long-term prognosis of these patients after discharge. Previous efforts to describe out-of-hospital survival of IHCA patients have been limited by small sample sizes and narrow patient populations Methods A single institution matched cohort study was undertaken to describe mortality following IHCA. Patients surviving to discharge following an IHCA between 2008 and 2010 were matched on age, sex, race and hospital admission criteria with non-IHCA hospital controls and follow-up between 9 and 45 months. Kaplan–Meier curves and Cox PH models assessed differences in survival. Results Of the 1262 IHCAs, 20% survived to hospital discharge. Of those discharged, survival at 1 year post-discharge was 59% for IHCA patients and 82% for controls (p < 0.0001). Hazard ratios (IHCA vs. controls) for mortality were greatest within the 90 days following discharge (HR = 2.90, p < 0.0001) and decreased linearly thereafter, with those surviving to one year post-discharge having an HR for mortality below 1.0. Survival after discharge varied amongst IHCA survivors. When grouped by discharge destination, out of hospital survival varied; in fact, IHCA patients discharged home without services demonstrated no survival difference compared to their non-IHCA controls (HR 1.10, p = 0.72). IHCA patients discharged to long-term hospital care or hospice, however, had a significantly higher mortality compared to matched controls (HR 3.91 and 20.3, respectively; p < 0.0001). Conclusion Among IHCA patients who survive to hospital discharge, the highest risk of death is within the first 90 days after discharge. Additionally, IHCA survivors overall have increased long-term mortality vs. controls. Survival rates were varied widely with different discharge destinations, and those discharged to home, skilled nursing facilities or to

  8. Implications of incomplete registration of deaths on long-term survival estimates from population-based cancer registries.

    PubMed

    Brenner, Hermann; Hakulinen, Timo

    2009-07-15

    International comparison of population-based cancer survival is a key component of monitoring progress against cancer. Its validity depends to an unknown degree on completeness of ascertainment of deaths in the cancer registries involved which may vary according to legal and administrative circumstances. The aim of this study was to assess the impact of incomplete registration of deaths through various mechanisms on the validity of long-term absolute and relative survival estimates. For that purpose, we simulated underascertainment of deaths through linkage failure of registry data with death certificates with probabilities between 0.1 and 5%, and underascertainment of deaths by unregistered annual emigration with probabilities between 0.05 and 2%, using data from the Finnish Cancer Registry. The expected impact on estimates of 5-, 10- and 15-year absolute and relative survival was assessed. We demonstrate that even modest levels of under-registration of deaths may lead to severe overestimation of long-term survival estimates, ranging from 0 to 31 percent units in the scenarios assessed. In general, relative survival is much more affected than absolute survival, and potential problems are much larger for relative survival estimates in older compared with younger patients. Potential overestimation strongly increases with length of follow-up, and this increase is particularly pronounced for under-registration of deaths because of unrecorded emigration. Every effort should be made in cancer registry based survival analyses to ascertain deaths with close to 100% completeness. When such completeness cannot be achieved, long-term relative survival estimates and their comparison across populations must be interpreted with much caution.

  9. Comparison of Long-term Survival of Implants and Endodontically Treated Teeth

    PubMed Central

    Setzer, F.C.; Kim, S.

    2014-01-01

    The outcomes of both dental implants and endodontically treated teeth have been extensively studied. However, there is still a great controversy over when to keep a natural tooth and when to extract it for a dental implant. This article reviews the benefits and disadvantages of both treatment options and discusses success vs. survival outcomes, as well as the impact of technical advances for modern endodontics and endodontic microsurgery on the long-term prognosis of tooth retention. PMID:24065635

  10. IDH-Mutation Is a Weak Predictor of Long-Term Survival in Glioblastoma Patients

    PubMed Central

    Amelot, Aymeric; De Cremoux, Patricia; Quillien, Véronique; Polivka, Marc; Adle-Biassette, Homa; Lehmann-Che, Jacqueline; Françoise, Laurence; Carpentier, Antoine F.; George, Bernard; Mandonnet, Emmanuel; Froelich, Sébastien

    2015-01-01

    Background A very small proportion of patients diagnosed with glioblastoma (GBM) survive more than 3 years. Isocitrate dehydrogenase 1 or 2 (IDH1/2) mutations define a small subgroup of GBM patients with favourable prognosis. However, it remains controversial whether long-term survivors (LTS) are found among those IDH1/2 mutated patients. Methods We retrospectively analyzed 207 GBM patients followed at Lariboisière Hospital (Paris) between 2005 and 2010. Clinical parameters were obtained from medical records. Mutations of IDH1/2 were analyzed in these patients, by immunohistochemistry for the R132H mutation of IDH1 and by high-resolution melting-curve analysis, followed by Sanger sequencing for IDH1 and IDH2 exon 4 mutations. Mutation rates in LTS and non-LTS groups were compared by Chi square Pearson test. Results Seventeen patients with survival >3 years were identified (8.2% of the total series). The median overall survival in long-term survivors was 4.6 years. Subgroup analysis found that the median age at diagnosis was significantly higher for non long-term survivors (non-LTS) compared to LTS (60 versus 51 years, p <0.03). The difference in the rate of IDH mutation between non-LTS and LTS was statistically not significant (1.16% versus 5.9%, p = 0.144). Among LTS, 10 out of 16 tumors presented a methylation of MGMT promoter. Conclusions This study confirms that long-term survival in GBM patients is if at all only weakly correlated to IDH-mutation. PMID:26158269

  11. Characterization of Ancient DNA Supports Long-Term Survival of Haloarchaea

    PubMed Central

    Lowenstein, Tim K.; Timofeeff, Michael N.; Schubert, Brian A.; Lum, J. Koji

    2014-01-01

    Abstract Bacteria and archaea isolated from crystals of halite 104 to 108 years old suggest long-term survival of halophilic microorganisms, but the results are controversial. Independent verification of the authenticity of reputed living prokaryotes in ancient salt is required because of the high potential for environmental and laboratory contamination. Low success rates of prokaryote cultivation from ancient halite, however, hamper direct replication experiments. In such cases, culture-independent approaches that use the polymerase chain reaction (PCR) and sequencing of 16S ribosomal DNA are a robust alternative. Here, we use amplification, cloning, and sequencing of 16S ribosomal DNA to investigate the authenticity of halophilic archaea cultured from subsurface halite, Death Valley, California, 22,000 to 34,000 years old. We recovered 16S ribosomal DNA sequences that are identical, or nearly so (>99%), to two strains, Natronomonas DV462A and Halorubrum DV427, which were previously isolated from the same halite interval. These results provide the best independent support to date for the long-term survival of halophilic archaea in ancient halite. PCR-based approaches are sensitive to small amounts of DNA and could allow investigation of even older halites, 106 to 108 years old, from which microbial cultures have been reported. Such studies of microbial life in ancient salt are particularly important as we search for microbial signatures in similar deposits on Mars and elsewhere in the Solar System. Key Words: Ancient DNA—Halite—Haloarchaea—Long-term survival. Astrobiology 14, 553–560. PMID:24977469

  12. Persistent poor long-term prognosis of allogeneic hematopoietic stem cell transplant recipients surviving invasive aspergillosis

    PubMed Central

    Salmeron, Géraldine; Porcher, Raphaël; Bergeron, Anne; Robin, Marie; de Latour, Régis Peffault; Ferry, Christèle; Rocha, Vanderson; Petropoulou, Anna; Xhaard, Aliénor; Lacroix, Claire; Sulahian, Annie; Socié, Gérard; Ribaud, Patricia

    2012-01-01

    Background Voriconazole treatment increases early survival of allogeneic hematopoietic stem cell transplant recipients with invasive aspergillosis. We investigated whether this survival advantage translates into an increased long-term survival. Design and Methods This retrospective study involved all patients with an invasive aspergillosis diagnosis transplanted between September 1997 and December 2008, at the Saint-Louis Hospital, Paris, France. The primary end point was survival up to 36 months. Survival analysis before and after 12 weeks, as well as cumulative incidence analysis in a competing risk framework, were used to assess the effect of voriconazole treatment and other factors on mortality. Results Among 87 patients, 42 received first-line voriconazole and 45 received another antifungal agent. Median survival time was 2.6 months and survival rate at 36 months was 18%. Overall, there was a significant difference in the survival rates of the two groups. Specifically, there was a dramatic difference in survival rates up to ten months post-aspergillosis diagnosis but no significant difference after this time. Over the first 36 months as a whole, no significant difference in survival rate was observed between the two groups. First-line voriconazole significantly reduced aspergillosis-attributable mortality. However, first-line voriconazole patients experienced a significantly higher probability of death from a non-aspergillosis-attributable cause. Conclusions Although the prognosis for invasive aspergillosis after stem cell transplantation has dramatically improved with the use of voriconazole, this major advance in care does not translate into increased long-term survival for these severely immunocompromised patients. PMID:22371177

  13. Physiological predictors of long-term survival in juvenile Steller sea lions (Eumetopias jubatus).

    PubMed

    Shuert, C; Mellish, J; Horning, M

    2015-01-01

    This study builds on a continued effort to document potential long-term research impacts on the individual, as well as to identify potential markers of survival for use in a field framework. The Transient Juvenile Steller sea lion (TJ) project was developed as a novel framework to gain access to wild individuals. We used three analyses to evaluate and predict long-term survival in temporarily captive sea lions (n = 45) through Cormack-Jolly-Seber open population modelling techniques. The first analysis investigated survival in relation to the observed responses to handling stress through changes in six principal blood parameters over the duration of captivity. The second analysis evaluated survival compared with body condition and mass at entry and exit from captivity. Finally, the third analysis sought to evaluate the efficacy of single-point sampling to project similar survival trends for use in field sampling operations. Results from a priori models ranked through Akaike information criterion model selection methods indicated that mass gains (4.2 ± 12%) over captivity and increases in leucocytes (WBC, 1.01 ± 3.54 × 10(3)/mm(3)) resulted in a higher average survival rate (>3 years). Minor support was identified for the single-point measures of exit mass and entry WBC. A higher exit mass predicted a higher survival rate, whereas a higher WBC predicted a lower survival rate. While changes in mass and WBC appear to be the best predictors of survival when measured as a change over time, single-point sampling may still be an effective way to improve estimates of population health.

  14. Physiological predictors of long-term survival in juvenile Steller sea lions (Eumetopias jubatus)

    PubMed Central

    Shuert, C.; Mellish, J.; Horning, M.

    2015-01-01

    This study builds on a continued effort to document potential long-term research impacts on the individual, as well as to identify potential markers of survival for use in a field framework. The Transient Juvenile Steller sea lion (TJ) project was developed as a novel framework to gain access to wild individuals. We used three analyses to evaluate and predict long-term survival in temporarily captive sea lions (n = 45) through Cormack–Jolly–Seber open population modelling techniques. The first analysis investigated survival in relation to the observed responses to handling stress through changes in six principal blood parameters over the duration of captivity. The second analysis evaluated survival compared with body condition and mass at entry and exit from captivity. Finally, the third analysis sought to evaluate the efficacy of single-point sampling to project similar survival trends for use in field sampling operations. Results from a priori models ranked through Akaike information criterion model selection methods indicated that mass gains (4.2 ± 12%) over captivity and increases in leucocytes (WBC, 1.01 ± 3.54 × 103/mm3) resulted in a higher average survival rate (>3 years). Minor support was identified for the single-point measures of exit mass and entry WBC. A higher exit mass predicted a higher survival rate, whereas a higher WBC predicted a lower survival rate. While changes in mass and WBC appear to be the best predictors of survival when measured as a change over time, single-point sampling may still be an effective way to improve estimates of population health. PMID:27293728

  15. Clinical Predictors of Long-term Survival in HER2-positive Metastatic Breast Cancer

    PubMed Central

    Murthy, Pooja; Kidwell, Kelley M.; Schott, Anne F.; Merajver, Sofia D.; Griggs, Jennifer J.; Smerage, Jeffrey D.; Van Poznak, Catherine H.; Wicha, Max S.; Hayes, Daniel F.; Henry, N. Lynn

    2016-01-01

    Purpose Prior to availability of anti-HER2 therapies, HER2-positive metastatic breast cancer (MBC) was associated with a poor prognosis. Prospective randomized trials have demonstrated survival benefit from anti-HER2 treatments. Anecdotal observations have suggested that a small but meaningful fraction of patients with HER2-positive MBC may be “exceptional responders” with long survival. We hypothesized that demographic and/or clinicopathologic characteristics can be identified to distinguish short-term from long-term survivors. Methods A retrospective, single institution review of 168 patients with HER2-positive MBC who received treatment with anti-HER2 therapy in the metastatic setting was performed. Cox proportional hazards analysis was used to assess factors associated with long-term survival. Results Median overall survival from the time of breast cancer recurrence was 3.9 years (95% CI 3.4–5.2). From the time of diagnosis of MBC, 56 (33%) survived for 5 or more years and 12 (7%) survived more than 10 years. Of the 66 patients diagnosed with central nervous system metastases, 9 (14%) survived more than 5 years following that diagnosis. Younger age at diagnosis, lower stage, hormone receptor positive status, and only having one organ involved at diagnosis were associated with longer survival. Four patients discontinued anti-HER2 therapy and are without evidence of progression of disease after a median 7.4 years (0.2–12.0) since stopping therapy. Conclusions In a cohort of patients with HER2-positive MBC treated primarily with trastuzumab and lapatinib, 7% of patients were “exceptional responders”. Combining these clinical factors associated with molecular determinants of prolonged survival with may provide insights for individualizing treatment selection. PMID:26875184

  16. Clinical predictors of long-term survival in HER2-positive metastatic breast cancer.

    PubMed

    Murthy, Pooja; Kidwell, Kelley M; Schott, Anne F; Merajver, Sofia D; Griggs, Jennifer J; Smerage, Jeffrey D; Van Poznak, Catherine H; Wicha, Max S; Hayes, Daniel F; Henry, N Lynn

    2016-02-01

    Prior to availability of anti-HER2 therapies, HER2-positive metastatic breast cancer (MBC) was associated with a poor prognosis. Prospective randomized trials have demonstrated survival benefit from anti-HER2 treatments. Anecdotal observations have suggested that a small but meaningful fraction of patients with HER2-positive MBC may be "exceptional responders" with long survival. We hypothesized that demographic and/or clinicopathologic characteristics can be identified to distinguish short-term from long-term survivors. A retrospective, single-institution review of 168 patients with HER2-positive MBC who received treatment with anti-HER2 therapy in the metastatic setting was performed. Cox proportional hazards analysis was used to assess factors associated with long-term survival. Median overall survival from the time of breast cancer recurrence was 3.9 years (95 % CI 3.4-5.2). From the time of diagnosis of MBC, 56 (33 %) survived for 5 or more years and 12 (7 %) survived more than 10 years. Of the 66 patients diagnosed with central nervous system metastases, 9 (14 %) survived more than 5 years following that diagnosis. Younger age at diagnosis, lower stage, hormone receptor positive status, and only having one organ involved at diagnosis were associated with longer survival. Four patients discontinued anti-HER2 therapy and are without evidence of progression of disease after a median 7.4 years (0.2-12.0) since stopping therapy. In a cohort of patients with HER2-positive MBC treated primarily with trastuzumab and lapatinib, 7 % of patients were "exceptional responders." Combining these clinical factors with molecular determinants of prolonged survival may provide insights for individualizing treatment selection.

  17. Conditional long-term survival following minimally invasive robotic mitral valve repair: a health services perspective

    PubMed Central

    Griffin, William F.; Gudimella, Preeti; O’Neal, Wesley T.; Davies, Stephen W.; Crane, Patricia B.; Anderson, Ethan J.; Kindell, Linda C.; Landrine, Hope; O’Neal, Jason B.; Alwair, Hazaim; Kypson, Alan P.; Nifong, Wiley L.; Chitwood, W. Randolph

    2015-01-01

    Background Conditional survival is defined as the probability of surviving an additional number of years beyond that already survived. The aim of this study was to compute conditional survival in patients who received a robotically assisted, minimally invasive mitral valve repair procedure (RMVP). Methods Patients who received RMVP with annuloplasty band from May 2000 through April 2011 were included. A 5- and 10-year conditional survival model was computed using a multivariable product-limit method. Results Non-smoking men (≤65 years) who presented in sinus rhythm had a 96% probability of surviving at least 10 years if they survived their first year following surgery. In contrast, recent female smokers (>65 years) with preoperative atrial fibrillation only had an 11% probability of surviving beyond 10 years if alive after one year post-surgery. Conclusions In the context of an increasingly managed healthcare environment, conditional survival provides useful information for patients needing to make important treatment decisions, physicians seeking to select patients most likely to benefit long-term following RMVP, and hospital administrators needing to comparatively assess the life-course economic value of high-tech surgical procedures. PMID:26539348

  18. Preoperative carcinoembryonic antigen is related to tumour stage and long-term survival in colorectal cancer.

    PubMed Central

    Chapman, M. A.; Buckley, D.; Henson, D. B.; Armitage, N. C.

    1998-01-01

    Evidence as to the value of preoperative carcinoembryonic antigen (CEA) in guiding treatment for patients with colorectal cancer is conflicting. The aim of this prospective study was to investigate the value of preoperative CEA in predicting tumour factors of proven prognostic value and long-term survival in patients undergoing surgery for colorectal cancer. Preoperative serum CEA, tumour ploidy, stage and grade were ascertained in 277 patients undergoing colorectal cancer surgery. This cohort of patients were followed up for a minimum of 5 years, or until death, in a dedicated colorectal clinic. Patients with an elevated CEA had a 5 year survival of 39%. This increased to 57% if the CEA was normal (P=0.001). The proportion of patients with a raised CEA increased with a more advanced tumour stage (P < 0.000001) and a poorly differentiated tumour grade (P < 0.005). Once stage had been controlled for, CEA was not a predictor of survival. No relationship between tumour ploidy and CEA was found. In conclusion, a raised preoperative serum CEA is likely to be associated with advanced tumour stage and poor long-term survival, compared with patients with a normal value. PMID:9823977

  19. Preoperative carcinoembryonic antigen is related to tumour stage and long-term survival in colorectal cancer.

    PubMed

    Chapman, M A; Buckley, D; Henson, D B; Armitage, N C

    1998-11-01

    Evidence as to the value of preoperative carcinoembryonic antigen (CEA) in guiding treatment for patients with colorectal cancer is conflicting. The aim of this prospective study was to investigate the value of preoperative CEA in predicting tumour factors of proven prognostic value and long-term survival in patients undergoing surgery for colorectal cancer. Preoperative serum CEA, tumour ploidy, stage and grade were ascertained in 277 patients undergoing colorectal cancer surgery. This cohort of patients were followed up for a minimum of 5 years, or until death, in a dedicated colorectal clinic. Patients with an elevated CEA had a 5 year survival of 39%. This increased to 57% if the CEA was normal (P=0.001). The proportion of patients with a raised CEA increased with a more advanced tumour stage (P < 0.000001) and a poorly differentiated tumour grade (P < 0.005). Once stage had been controlled for, CEA was not a predictor of survival. No relationship between tumour ploidy and CEA was found. In conclusion, a raised preoperative serum CEA is likely to be associated with advanced tumour stage and poor long-term survival, compared with patients with a normal value.

  20. Long-term survival after coronary bypass surgery and percutaneous coronary intervention

    PubMed Central

    Mølstad, Per; Moer, Rasmus; Rødevand, Olaf

    2016-01-01

    Objectives To assess whether there exists a long-term difference in survival after treatment with coronary bypass surgery or percutaneous coronary intervention in patients with coronary disease as judged by all-cause mortality. Methods Retrospective study from the Feiring Heart Clinic database of survival in 22 880 patients—15 078 treated with percutaneous coronary intervention and 7802 with bypass surgery followed up to 16 years. Results Cox regression and propensity score analysis showed no difference in survival for one-vessel and two-vessel disease during the whole study period. In three-vessel disease, however, the analysis revealed a consistent and highly significant survival benefit in the first 8 years with an HR of 0.76 (95% CI 0.69 to 0.84, p<0.001) in favour of bypass surgery with similar survival rates in the two treatment strategies after that time period. Conclusions Treatment strategy did not affect survival in one-vessel and two-vessel disease, but bypass surgery offered an improved survival in the first 8 years in patients with three-vessel disease. These results are consistent with most previous reports and the survival benefit should be taken into account when selecting a strategy for this patient group. PMID:27843567

  1. Long-Term Survival of Patients Receiving Artificial Nutrition in Japanese Psychiatric Hospitals

    PubMed Central

    Abe, Keiichi; Yamashita, Ryuko; Kondo, Keiko; Takayama, Keiko; Yokota, Osamu; Sato, Yoshiki; Kawai, Mitsumasa; Ishizu, Hideki; Nakashima, Tadao; Hayashi, Hideki; Nakata, Kenji; Asaba, Hiroyuki; Kadota, Koichi; Tanaka, Kazuyoshi; Morisada, Yumi; Oshima, Etsuko; Terada, Seishi

    2016-01-01

    Background/Aims Most patients with dementia suffer from dysphagia in the terminal stage of the disease. In Japan, most elderly patients with dysphagia receive either tube feeding or total parenteral nutrition. Methods In this study, we investigated the factors determining longer survival with artificial nutrition. Various clinical characteristics of 168 inpatients receiving artificial nutrition without oral intake in psychiatric hospitals in Okayama Prefecture, Japan, were evaluated. Results Multiple logistic regression analysis showed that the duration of artificial nutrition was associated with a percutaneous endoscopic gastrostomy (PEG) tube, diagnosis of mental disorder, low MMSE score, and absence of decubitus. Conclusion Patients with mental disorders survived longer than those with dementia diseases on artificial nutrition. A PEG tube and good nutrition seem to be important for long-term survival. PMID:27843445

  2. Extremely halophilic archaea from ancient salt sediments and their long term survival.

    NASA Astrophysics Data System (ADS)

    Stan-Lotter, Helga; Fendrihan, Sergiu; Dornmayr-Pfaffenhuemer, Marion

    Halophilic archaebacteria (haloarchaea) thrive in environments with salt concentrations approaching saturation, such as natural brines, marine solar salterns and alkaline salt lakes; they have also been isolated from rock salt of great geological age (195-250 million years) and some of those strains were described as novel species (1). The cells survived perhaps while being enclosed within small fluid inclusions in the halite. When simulating the embedding process of haloarchaea in laboratory-grown salt crystals, cells accumulated preferentially in fluid inclusions, as could be demonstrated by pre-staining with fluorescent dyes. The issue of extreme long term microbial survival in rock salt has considerable implications for the search for extraterrestrial life. Halite has been found in Martian meteorites, salts are present on the Martian surface and there is good evidence for a salty ocean on the Jovian moon Europa. Therefore the search for halophilic prokaryotic life in such environments appears plausible. The development of detection methods for subsurface haloarchaea, which might also be applicable to samples from future missions to space, is important and some examples such as fluorescence microscopy methods with novel dyes will be described. (1) Fendrihan, S., Legat, A., Gruber, C., Pfaffenhuemer, M., Weidler, G., Gerbl, F., Stan- Lotter, H. (2006) Extremely halophilic archaea and the issue of long term microbial survival. Reviews in Environmental Science and Bio/technology 5, 1569-1605.

  3. Factors associated with long-term survival after liver transplantation: A retrospective cohort study

    PubMed Central

    Pischke, Sven; Lege, Marie C; von Wulffen, Moritz; Galante, Antonio; Otto, Benjamin; Wehmeyer, Malte H; Herden, Uta; Fischer, Lutz; Nashan, Björn; Lohse, Ansgar W; Sterneck, Martina

    2017-01-01

    AIM To identify predictive factors associated with long-term patient and graft survival (> 15 years) in liver transplant recipients. METHODS Medical charts of all de novo adult liver transplant recipients (n = 140) who were transplanted in Hamburg between 1997 and 1999 were retrospectively reviewed. In total, 155 transplantations were identified in this time period (15 re-transplantations). Twenty-six orthotopic liver transplant (OLT) recipients were early lost to follow-up due to moving to other places within 1 year after transplantation. All remaining 114 patients were included in the analysis. The following recipient factors were analysed: Age, sex, underlying liver disease, pre-OLT body mass index (BMI), and levels of alanine aminotransferase (ALT), bilirubin, creatinine and gamma-glutamyltransferase (gamma-GT), as well as warm and cold ischemia times. Furthermore, the following donor factors were assessed: Age, BMI, cold ischemia time and warm ischemia time. All surviving patients were followed until December 2014. We divided patients into groups according to their underlying diagnosis: (1) hepatocellular carcinoma (n = 5, 4%); (2) alcohol toxic liver disease (n = 25, 22.0%); (3) primary sclerosing cholangitis (n = 6, 5%); (4) autoimmune liver diseases (n = 7, 6%); (5) hepatitis C virus cirrhosis (n = 15, 13%); (6) hepatitis B virus cirrhosis (n = 21, 19%); and (7) other (n = 35, 31%). The group “other” included rare diagnoses, such as acute liver failure, unknown liver failure, stenosis and thrombosis of the arteria hepatica, polycystic liver disease, Morbus Osler and Caroli disease. RESULTS The majority of patients were male (n = 70, 61%). Age and BMI at the time point of transplantation ranged from 16 years to 69 years (median: 53 years) and from 15 kg/m2 to 33 kg/m2 (median: 24), respectively. Sixty-six OLT recipients (58%) experienced a follow-up of 15 years after transplantation. Recipient’s age (P = 0.009) and BMI (P = 0.029) were identified as

  4. Molecular Predictors of Long-Term Survival in Glioblastoma Multiforme Patients

    PubMed Central

    Cowperthwaite, Matthew C.; Burnett, Mark G.; Shpak, Max

    2016-01-01

    Glioblastoma multiforme (GBM) is the most common and aggressive adult primary brain cancer, with <10% of patients surviving for more than 3 years. Demographic and clinical factors (e.g. age) and individual molecular biomarkers have been associated with prolonged survival in GBM patients. However, comprehensive systems-level analyses of molecular profiles associated with long-term survival (LTS) in GBM patients are still lacking. We present an integrative study of molecular data and clinical variables in these long-term survivors (LTSs, patients surviving >3 years) to identify biomarkers associated with prolonged survival, and to assess the possible similarity of molecular characteristics between LGG and LTS GBM. We analyzed the relationship between multivariable molecular data and LTS in GBM patients from the Cancer Genome Atlas (TCGA), including germline and somatic point mutation, gene expression, DNA methylation, copy number variation (CNV) and microRNA (miRNA) expression using logistic regression models. The molecular relationship between GBM LTS and LGG tumors was examined through cluster analysis. We identified 13, 94, 43, 29, and 1 significant predictors of LTS using Lasso logistic regression from the somatic point mutation, gene expression, DNA methylation, CNV, and miRNA expression data sets, respectively. Individually, DNA methylation provided the best prediction performance (AUC = 0.84). Combining multiple classes of molecular data into joint regression models did not improve prediction accuracy, but did identify additional genes that were not significantly predictive in individual models. PCA and clustering analyses showed that GBM LTS typically had gene expression profiles similar to non-LTS GBM. Furthermore, cluster analysis did not identify a close affinity between LTS GBM and LGG, nor did we find a significant association between LTS and secondary GBM. The absence of unique LTS profiles and the lack of similarity between LTS GBM and LGG, indicates

  5. Long-Term Survival of an Urban Fruit Bat Seropositive for Ebola and Lagos Bat Viruses

    PubMed Central

    Hayman, David T. S.; Emmerich, Petra; Yu, Meng; Wang, Lin-Fa; Suu-Ire, Richard; Fooks, Anthony R.; Cunningham, Andrew A.; Wood, James L. N.

    2010-01-01

    Ebolaviruses (EBOV) (family Filoviridae) cause viral hemorrhagic fevers in humans and non-human primates when they spill over from their wildlife reservoir hosts with case fatality rates of up to 90%. Fruit bats may act as reservoirs of the Filoviridae. The migratory fruit bat, Eidolon helvum, is common across sub-Saharan Africa and lives in large colonies, often situated in cities. We screened sera from 262 E. helvum using indirect fluorescent tests for antibodies against EBOV subtype Zaire. We detected a seropositive bat from Accra, Ghana, and confirmed this using western blot analysis. The bat was also seropositive for Lagos bat virus, a Lyssavirus, by virus neutralization test. The bat was fitted with a radio transmitter and was last detected in Accra 13 months after release post-sampling, demonstrating long-term survival. Antibodies to filoviruses have not been previously demonstrated in E. helvum. Radio-telemetry data demonstrates long-term survival of an individual bat following exposure to viruses of families that can be highly pathogenic to other mammal species. Because E. helvum typically lives in large urban colonies and is a source of bushmeat in some regions, further studies should determine if this species forms a reservoir for EBOV from which spillover infections into the human population may occur. PMID:20694141

  6. Characterization of ancient DNA supports long-term survival of Haloarchaea.

    PubMed

    Sankaranarayanan, Krithivasan; Lowenstein, Tim K; Timofeeff, Michael N; Schubert, Brian A; Lum, J Koji

    2014-07-01

    Bacteria and archaea isolated from crystals of halite 10(4) to 10(8) years old suggest long-term survival of halophilic microorganisms, but the results are controversial. Independent verification of the authenticity of reputed living prokaryotes in ancient salt is required because of the high potential for environmental and laboratory contamination. Low success rates of prokaryote cultivation from ancient halite, however, hamper direct replication experiments. In such cases, culture-independent approaches that use the polymerase chain reaction (PCR) and sequencing of 16S ribosomal DNA are a robust alternative. Here, we use amplification, cloning, and sequencing of 16S ribosomal DNA to investigate the authenticity of halophilic archaea cultured from subsurface halite, Death Valley, California, 22,000 to 34,000 years old. We recovered 16S ribosomal DNA sequences that are identical, or nearly so (>99%), to two strains, Natronomonas DV462A and Halorubrum DV427, which were previously isolated from the same halite interval. These results provide the best independent support to date for the long-term survival of halophilic archaea in ancient halite. PCR-based approaches are sensitive to small amounts of DNA and could allow investigation of even older halites, 10(6) to 10(8) years old, from which microbial cultures have been reported. Such studies of microbial life in ancient salt are particularly important as we search for microbial signatures in similar deposits on Mars and elsewhere in the Solar System.

  7. Covert deformed wing virus infections have long-term deleterious effects on honeybee foraging and survival.

    PubMed

    Benaets, Kristof; Van Geystelen, Anneleen; Cardoen, Dries; De Smet, Lina; de Graaf, Dirk C; Schoofs, Liliane; Larmuseau, Maarten H D; Brettell, Laura E; Martin, Stephen J; Wenseleers, Tom

    2017-02-08

    Several studies have suggested that covert stressors can contribute to bee colony declines. Here we provide a novel case study and show using radiofrequency identification tracking technology that covert deformed wing virus (DWV) infections in adult honeybee workers seriously impact long-term foraging and survival under natural foraging conditions. In particular, our experiments show that adult workers injected with low doses of DWV experienced increased mortality rates, that DWV caused workers to start foraging at a premature age, and that the virus reduced the workers' total activity span as foragers. Altogether, these results demonstrate that covert DWV infections have strongly deleterious effects on honeybee foraging and survival. These results are consistent with previous studies that suggested DWV to be an important contributor to the ongoing bee declines in Europe and the USA. Overall, our study underlines the strong impact that covert pathogen infections can have on individual and group-level performance in bees.

  8. Mesothelioma patients with germline BAP1 mutations have 7-fold improved long-term survival.

    PubMed

    Baumann, Francine; Flores, Erin; Napolitano, Andrea; Kanodia, Shreya; Taioli, Emanuela; Pass, Harvey; Yang, Haining; Carbone, Michele

    2015-01-01

    BRCA1-associated protein-1 (BAP1) mutations cause a new cancer syndrome, with a high rate of malignant mesothelioma (MM). Here, we tested the hypothesis that MM associated with germline BAP1 mutations has a better prognosis compared with sporadic MM. We compared survival among germline BAP1 mutation MM patients with that of all MM (N = 10 556) recorded in the United States Surveillance, Epidemiology, and End Results (SEER) data from 1973 to 2010. We identified 23 MM patients--11 alive--with germline BAP1 mutations and available data on survival. Ten patients had peritoneal MM, ten pleural MM and three MM in both locations. Thirteen patients had one or more malignancies in addition to MM. Actuarial median survival for the MM patients with germline BAP1 mutations was 5 years, as compared with <1 year for the median survival in the United States SEER MM group. Five-year survival was 47%, 95% confidence interval (24-67%), as compared with 6.7% (6.2-7.3%) in the control SEER group. Analysis of the pooled cohort of germline BAP1 mutation MM showed that patients with peritoneal MM (median survival of 10 years, P = 0.0571), or with a second malignancy in addition to MM (median survival of 10 years, P = 0.0716), survived for a longer time compared with patients who only had pleural MM, or MM patients without a second malignancy, respectively. In conclusion, we found that MM patients with germline BAP1 mutations have an overall 7-fold increased long-term survival, independently of sex and age. Appropriate genetic counseling and clinical management should be considered for MM patients who are also BAP1 mutation carriers.

  9. Pets, depression and long term survival in community living patients following myocardial infarction

    PubMed Central

    Friedmann, Erika; Thomas, Sue A.; Son, Heesook

    2011-01-01

    Evidence supports the contribution of depression, anxiety, and poor social support to mortality of hospitalized myocardial infarction (MI) patients. The contribution of depression to survival is independent of disease severity. Pet ownership, a non-human form of social support, has also been associated with one year survival of post-MI patients. The current study addresses whether pet ownership contributes independently to long term survival beyond the contributions of depression, anxiety, or low social support in post-MI patients who have already survived at least 6 months. Data from patients (N = 460) enrolled in the “Psychosocial Responses in the Home Automated External Defibrillator Trial (PR-HAT)”were used. Seventeen patients died during a median follow-up of 2.8 years. In Cox proportional hazards regression model that included depression, lack of pet ownership, and the interaction between depression and lack of pet ownership, not owning a pet was the only significant independent predictor of mortality (p = 0.036). The interaction between pet ownership and depression tended to be significant indicating that the effect of pet ownership on survival in this group of people who have supportive spouses/companions living with them may relate to depression. PMID:21857770

  10. Glycated Albumin Predicts Long-term Survival in Patients Undergoing Hemodialysis

    PubMed Central

    Lu, Chien-Lin; Ma, Wen-Ya; Lin, Yuh-Feng; Shyu, Jia-Fwu; Wang, Yuan-Hung; Liu, Yueh-Min; Wu, Chia-Chao; Lu, Kuo-Cheng

    2016-01-01

    Background: In patients with advanced renal dysfunction undergoing maintenance hemodialysis, glycated albumin (GA) levels may be more representative of blood glucose levels than hemoglobin A1C levels. The aim of this study was to determine the predictive power of GA levels on long-term survival in hemodialysis patients. Methods: A total of 176 patients with a mean age of 68.2 years were enrolled. The median duration of follow-up was 51.0 months. Receiver-operating characteristic curve analysis was utilized to determine the optimal cutoff value. We examined the cumulative survival rate by Kaplan-Meier estimates and the influence of known survival factors with the multivariate Cox proportional-hazard regression model. Results: In the whole patient group, cumulative survival in the low GA group was better than in the high GA group (p=0.030), with more prominence in those aged <70 years (p=0.029). In subgroup analysis, both diabetic (DM) and non-DM patients with low GA had a better cumulative survival compared with those with high GA. The risk of mortality increased by 3.0% for each 1% increase in serum GA level in all patients undergoing hemodialysis. Conclusions: In addition to serving as a glycemic control marker, GA levels may be useful for evaluating the risk of death in both DM and non-DM patients on hemodialysis. PMID:27226780

  11. Contrasting long-term survival of two outplanted Mojave Desert perennials for post-fire revegetation

    USGS Publications Warehouse

    Scoles-Sciulla, Sara J.; Defalco, Lesley A.; Esque, Todd C.

    2015-01-01

    Post-fire recovery of arid shrublands is typically slow, and planting greenhouse-raised seedlings may be a means of jump-starting this process. Recovery can be further accelerated by understanding the factors controlling post-planting survival. In fall 2007 and 2009, we outplanted seedlings of two contrasting native evergreen shrubs—fast-growing Nevada jointfir and slow-growing blackbrush—across five burned sites in the Mojave Desert. To increase soil moisture and optimize seedling survival, we experimentally applied and evaluated soil amendments and supplemental watering. We also evaluated two herbicides that reduce competitive invasive annual grasses and two types of herbivore protection. Survival of jointfir outplanted in 2007 was 61% after 43 months, and site largely influenced survival, while herbicide containing imazapic applied more than one year after outplanting reduced survival. Reduced survival of jointfir outplanted in 2009 coincided with delayed seasonal precipitation that intensified foliar damage by small mammals. In contrast, blackbrush survival was 4% after 43 months, and was influenced by site, type of herbivore protection, and greenhouse during the 2007 outplanting, and soil amendment during 2009. Counter to expectations, we found that supplemental watering and soil amendments did not influence long-term survival of either blackbrush or jointfir. Shrub species with rapid growth rates and broad environmental tolerances, such as jointfir, make ideal candidates for outplanting, provided that seedlings are protected from herbivores. Re-introduction of species with slow growth rates and narrow environmental tolerances, such as blackbrush, requires careful consideration to optimize pre- and post-planting conditions.

  12. [Effect of long-term therapy with oral Beraprost on survival of patients with arterial and inoperable thromboembolic pulmonary hypertension].

    PubMed

    Kurzyna, Marcin; Florczyk, Michał; Fijałkowska, Anna; Kuca, Paweł; Szewczyk, Grzegorz; Burakowski, Janusz; Kober, Jarosław; Sikora, Jarosław; Wawrzyńska, Liliana; Szturmowicz, Monika; Tomkowskil, Witold; Torbicki, Adam

    2004-04-01

    Beraprost sodium (BPS)--an orally active prostacyclin analogue--improves haemodynamic parameters and quality of life in group of patients with pulmonary arterial hypertension. Effect of long-term therapy with BPS is not well defined. This study assesses influence of long-term therapy with BPS on the survival of patients with precapillary pulmonary hypertension. Studied group consisted of 25 patients with precapillary PH (18 F, 7M, aged 34 +/- 13,9 years). Sixteen patients were diagnosed with primary PH, 3 pts had PH associated with connective tissue disease, 5 pts developed PH in course of congenital systemic to pulmonary shunt, and 1 patient suffered from inoperable chronic thromboembolic PH. At time of diagnosis 15 pts presented exercise impairment of WHO class II and 10 pts were in functional class III. All studied subjects had complete hemodynamic assessment of right heart and obtained values were used for estimation of hypothetic survival using prognostic equation proposed by D'Alonzo et al. On follow-up period patients received BPS in the highest tolerated dose (80-480 mg daily). During a follow-up period (mean: 22 months) 7 patients died. Cumulative survival rate BPS group was significantly higher in BPS group comparing to hypothetical survival at 6 months (96% (95% CI: 88-104%) vs 73% (95% CI: 67-78%), p = 0.02) and 12 months (94% (95% CI: 84-104%) vs 65% (58-71%), p = 0.01), respectively. At 18 and 24 months differences between BPS virtual and hypothetical survival were not statistically significant. There was no correlation between survival and maximal achieved dose of BPS. These results suggest, that BPS improves prognosis of patients with precapillary PH during 12 months after initiation of therapy. Later effect of BPS seems to decrease, requiring changing or intensification of therapy.

  13. Pathobiology of breast cancer: hypothesis of biological predetermination and long-term survival.

    PubMed

    Vorherr, H

    1981-08-03

    Th pathobiology of breast cancer is complex: clinically "early" breast cancer may be tumor biologically "late" progressing rapidly toward death. Accordingly, it has been suggested that two different breast cancer populations (slow tumor growth and long survival-fast tumor growth and short survival) exist, which cannot be identified by pathohistological criteria. However, these "populations" are most likely either patients with localized disease and occult metastases (long survival) or with diagnosable regional and occult or overt systemic spread (short survival). Since even small tumors (0.1 to 0.3 cm in diameter) can spread systemically, in most patients breast cancer upon clinical diagnosis may be considered an inevitably lethal disease. Present treatment modalities can only improve the quality of life and delay death, even though the overall long-term survival rates of breast cancer are better or at least equal to those of other cancers. However, with other cancers (Table 2) it is decided within the first 5 years which patients are cured because the survival rates for 5, 10, 15, and 20 years are similar. In contrast, survival rates of patients with breast cancer steadily decline and there is no point in time when patients can feel really safe; this is indicative of a peculiar tumor pathobiology of this disease, the nature of which remains to be investigated. Progress in the fight against breast cancer is only possible by application of sensitive physical, reliable immunological, and specific biochemical methods for early diagnosis and development of efficient therapeutic modalities for inhibition of growth or complete eradication of metastasized cancer cells.

  14. Long term survival of radiotherapy for esophageal cancer: analysis of 1136 patients surviving for more than 5 years

    SciTech Connect

    Yang, Z.Y.; Gu, X.; Zhao, S.

    1983-12-01

    One thousand one hundred and thirty-six patients surviving for more than five years after radiotherapy were studied. The important prognostic factors are: lesion less than 5 cm in length, lesion located in the upper-third segment and lesion that is radiosensitive. The radiation dose given to long term survivors varies greatly, i.e., 2700 to 9300 rad. Yet, for the sensitive type of lesion, doses lower than 5000 rad could also effect a cure. The delivery of an optimum dose determined by serial examinations during radiotherapy could improve the result of treatment. For local recurrent lesions, the value of a second course of radiation is extremely limited and surgery is the only means to offer a cure. For metastasis in the lymph nodes, radiation offers some hope of cure, although the long term outcome may not be satisfactory. For second primary cancer of the esophagus, aggressive radiation still gives encouraging results.

  15. A thermal control system for long-term survival of scientific instruments on lunar surface.

    PubMed

    Ogawa, K; Iijima, Y; Sakatani, N; Otake, H; Tanaka, S

    2014-03-01

    A thermal control system is being developed for scientific instruments placed on the lunar surface. This thermal control system, Lunar Mission Survival Module (MSM), was designed for scientific instruments that are planned to be operated for over a year in the future Japanese lunar landing mission SELENE-2. For the long-term operations, the lunar surface is a severe environment because the soil (regolith) temperature varies widely from nighttime -200 degC to daytime 100 degC approximately in which space electronics can hardly survive. The MSM has a tent of multi-layered insulators and performs a "regolith mound". Temperature of internal devices is less variable just like in the lunar underground layers. The insulators retain heat in the regolith soil in the daylight, and it can keep the device warm in the night. We conducted the concept design of the lunar survival module, and estimated its potential by a thermal mathematical model on the assumption of using a lunar seismometer designed for SELENE-2. Thermal vacuum tests were also conducted by using a thermal evaluation model in order to estimate the validity of some thermal parameters assumed in the computed thermal model. The numerical and experimental results indicated a sufficient survivability potential of the concept of our thermal control system.

  16. A thermal control system for long-term survival of scientific instruments on lunar surface

    NASA Astrophysics Data System (ADS)

    Ogawa, K.; Iijima, Y.; Sakatani, N.; Otake, H.; Tanaka, S.

    2014-03-01

    A thermal control system is being developed for scientific instruments placed on the lunar surface. This thermal control system, Lunar Mission Survival Module (MSM), was designed for scientific instruments that are planned to be operated for over a year in the future Japanese lunar landing mission SELENE-2. For the long-term operations, the lunar surface is a severe environment because the soil (regolith) temperature varies widely from nighttime -200 degC to daytime 100 degC approximately in which space electronics can hardly survive. The MSM has a tent of multi-layered insulators and performs a "regolith mound". Temperature of internal devices is less variable just like in the lunar underground layers. The insulators retain heat in the regolith soil in the daylight, and it can keep the device warm in the night. We conducted the concept design of the lunar survival module, and estimated its potential by a thermal mathematical model on the assumption of using a lunar seismometer designed for SELENE-2. Thermal vacuum tests were also conducted by using a thermal evaluation model in order to estimate the validity of some thermal parameters assumed in the computed thermal model. The numerical and experimental results indicated a sufficient survivability potential of the concept of our thermal control system.

  17. Poor biofilm-forming ability and long-term survival of invasive Salmonella Typhimurium ST313.

    PubMed

    Ramachandran, Girish; Aheto, Komi; Shirtliff, Mark E; Tennant, Sharon M

    2016-07-01

    Salmonella enterica serovar Typhimurium, an enteric pathogen that causes a self-limiting gastroenteritis, forms biofilms on different surfaces. In sub-Saharan Africa, Salmonella Typhimurium of a novel sequence type (ST) 313 was identified and produces septicemia in the absence of gastroenteritis. No animal reservoir has been identified, and it is hypothesized that transmission occurs via human to human. In this study, we show that invasive Salmonella Typhimurium ST313 strains from Mali are poor biofilm producers compared to Salmonella Typhimurium ST19 strains, which are found worldwide and are known to be associated with gastroenteritis. We evaluated biofilms using crystal violet staining, examination of the red, dry and rough morphotype, pellicle formation and a continuous flow system. One month-old Salmonella Typhimurium ST19 colonies survived in the absence of exogenous nutrients and were highly resistant to sodium hypochlorite treatment compared to Salmonella Typhimurium ST313. This study for the first time demonstrates the comparative biofilm-forming ability and long-term survival of clinical Salmonella Typhimurium ST19 and ST313 isolates. Salmonella Typhimurium ST19 strains are strong biofilm producers and can survive desiccation compared to Salmonella Typhimurium ST313 that form weak biofilms and survive poorly following desiccation. Our data suggest that like Salmonella Typhi, Salmonella Typhimurium ST313 lack mechanisms that allow it to persist in the environment.

  18. A thermal control system for long-term survival of scientific instruments on lunar surface

    SciTech Connect

    Ogawa, K.; Iijima, Y.; Tanaka, S.; Sakatani, N.; Otake, H.

    2014-03-15

    A thermal control system is being developed for scientific instruments placed on the lunar surface. This thermal control system, Lunar Mission Survival Module (MSM), was designed for scientific instruments that are planned to be operated for over a year in the future Japanese lunar landing mission SELENE-2. For the long-term operations, the lunar surface is a severe environment because the soil (regolith) temperature varies widely from nighttime −200 degC to daytime 100 degC approximately in which space electronics can hardly survive. The MSM has a tent of multi-layered insulators and performs a “regolith mound”. Temperature of internal devices is less variable just like in the lunar underground layers. The insulators retain heat in the regolith soil in the daylight, and it can keep the device warm in the night. We conducted the concept design of the lunar survival module, and estimated its potential by a thermal mathematical model on the assumption of using a lunar seismometer designed for SELENE-2. Thermal vacuum tests were also conducted by using a thermal evaluation model in order to estimate the validity of some thermal parameters assumed in the computed thermal model. The numerical and experimental results indicated a sufficient survivability potential of the concept of our thermal control system.

  19. Aggressive resection of frequent peritoneal recurrences in colorectal cancer contributes to long-term survival

    PubMed Central

    Komori, Koji; Kinoshita, Takashi; Taihei, Oshiro; Ito, Seiji; Abe, Tetsuya; Senda, Yoshiki; Misawa, Kazunari; Ito, Yuich; Uemura, Norihisa; Natsume, Seiji; Kawakami,, Jiro; Ouchi, Akira; Tsutsuyama, Masayuki; Hosoi, Takahiro; Shigeyoshi, Itaru; Akazawa, Tomoyuki; Hayashi, Daisuke; Tanaka, Hideharu; Shimizu, Yasuhiro

    2016-01-01

    ABSTRACT We report a long-term survivor of colorectal cancer who underwent aggressive, frequent resection for peritoneal recurrences. A 58-year-old woman was diagnosed with descending colon cancer. Resection of the descending colon along with lymph node dissection was performed in September 2006. The pathological findings revealed Stage IIA colorectal cancer. The following peritoneal recurrences were removed: two in July 2007, two in the omental fat and two in the pouch of Douglas in June 2008 resected by low anterior resection of the rectum, one in the uterus and right ovarian recurrence resected via bilateral adnexectomy and Hartmann’s procedure in May 2011, and one in the ascending colon by partial resection of the colon wall in December 2011. Postoperative adjuvant chemotherapy (uracil and tegafur/leucovorin, fluorouracil/levofolinate/oxaliplatin/bevacizumab, 5-fluorouracil/leucovorin/bevacizumab, irinotecan/bevacizumab, and irinotecan/panitumumab) was administered. The patient did not desire postoperative adjuvant chemotherapy after the fourth operation. The long-term survival was 6 years and 7 months. PMID:28008206

  20. Survival of dormant organisms after long-term exposure to the space environment

    NASA Astrophysics Data System (ADS)

    Novikova, N.; Gusev, O.; Polikarpov, N.; Deshevaya, E.; Levinskikh, M.; Alekseev, V.; Okuda, T.; Sugimoto, M.; Sychev, V.; Grigoriev, А.

    2011-05-01

    The RF SRC—Institute of Biomedical Problems, Russian Academy of Sciences, developed Biorisk hardware to study the effects of long-term exposure of dormant forms of various organisms to outer space and used it to complete a series of experiments on the Russian Module (RM) of the International Space Station (ISS). The experiments were performed using prokaryotes ( Bacillus bacteria) and eukaryotes ( Penicillium, Aspergillus, and Cladosporium fungi), as well as spores, dormant forms of higher plants, insects, lower crustaceans, and vertebrates. The biological samples were housed in two containers that were exposed to outer space for 13 or 18 months. The results of the 18-month experiment showed that, in spite of harsher temperature than in the first study, most specimens remained viable. These experiments provided evidence that not only bacterial and fungal spores but also dormant forms of organisms that reached higher levels of evolutionary development had the capability to survive a long-term exposure to outer space. This observation suggests that they can be transferred on outer walls of space platforms during interplanetary missions.

  1. Physical Activity and Survival among Long-term Cancer Survivor and Non-Cancer Cohorts

    PubMed Central

    Gunnell, Anthony S.; Joyce, Sarah; Tomlin, Stephania; Taaffe, Dennis R.; Cormie, Prue; Newton, Robert U.; Joseph, David; Spry, Nigel; Einarsdóttir, Kristjana; Galvão, Daniel A.

    2017-01-01

    Evidence suggests physical activity improves prognosis following cancer diagnosis; however, evidence regarding prognosis in long-term survivors of cancer is scarce. We assessed physical activity in 1,589 cancer survivors at an average 8.8 years following their initial diagnosis and calculated their future mortality risk following physical activity assessment. We also selected a cancer-free cohort of 3,145 age, sex, and survey year group-matched cancer-free individuals from the same source population for comparison purposes. Risks for cancer-specific mortality and all-cause mortality in relation to physical activity levels were estimated using Cox regression proportional hazard regression analyses within the cancer and non-cancer cohorts. Physical activity levels of 360+ min per week were inversely associated with cancer-specific mortality in long-term cancer survivors [hazard ratios (HR) = 0.30 (95% confidence intervals (CI) 0.13–0.70)] and participants without prior cancer [HR = 0.16 (95% CI 0.05–0.56)] compared with no reported physical activity. Physical activity levels of 150–359 and 360+ min were inversely associated with all-cause mortality in long-term cancer survivors [150–359 min; HR = 0.55 (95% CI 0.31–0.97), 360+ min; HR = 0.41 (95% CI 0.21–0.79)] and those without prior cancer [150–359 min; HR = 0.52 (95% CI 0.32–0.86), 360+ min; HR = 0.50 (95% CI 0.29–0.88)]. These results suggest that meeting exercise guidelines of 150 min of physical activity per week were associated with reduced all-cause mortality in both long-term cancer surviving and cancer-free cohorts. Exceeding exercise oncology guidelines (360+ min per week) may provide additional protection in terms of cancer-specific death. PMID:28261579

  2. Laboratory and Field Evidence for Long-Term Starvation Survival of Microorganisms in Subsurface Terrestrial Environments

    SciTech Connect

    Kieft, T.L.; Murphy, E.M.; Amy, P.S.; Haldeman, D.L.; Ringelberg, D. B. |

    1997-12-31

    BIOGEOCHEMICAL MODELING OF GROUNDWATER FLOW AND NUTRIENT FLUX IN SUBSURFACE ENVIRONMENTS INDICATES THAT INHABITANT MICROORGANISMS EXPERIENCE SEVERE NUTRIENT LIMITATION. USING LABORATORY AND FIELD METHODS, WE HAVE BEEN TESTING STARVATION SURVIVAL IN SUBSURFACE MICROORGANISMS. IN MICROCOSM EXPERIMENTS, WE HAVE SHOWN THAT STRAINS OF TWO COMMONLY ISOLATED SUBSURFACE GENERA, ARTHROBACTER AND PSEUDOMONAS, ARE ABLE TO MAINTAIN VIABILITY IN LOW-NUTRIENT, NATURAL SUBSURFACE SEDIMENTS FOR OVER ONE YEAR. THESE NON-SPORE-FORMING BACTERIA UNDERGO RAPID INITIAL MINIATURIZATION FOLLOWED BY A STABILIZATION OF CELL SIZE. MEMBRANE LIPID PHOSPHOLIPID FATTY ACID (PLFA) PROFILES OF THE PSEUDOMONAS ARE CONSISTENT WITH ADAPTATION TO NUTRIENT STRESS; ARTHROBACTER APPARENTLY RESPONDS TO NUTRIENT DEPRIVATION WITHOUT ALTERING MEMBRANE PLFA. TO TEST SURVIVABILITY OF MICROORGANISMS OVER A GEOLOGIC TIME SCALE, WE CHARACTERIZED MICROBIAL COMMUNITIES IN A SEQUENCE OF UNSATURATED SEDIMENTS RANGING IN AGE FROM MODEM TO {gt}780,000 years. Sediments were relatively uniform silts in Eastern Washington State. Porewater ages at depth (measured by the chloride mass-balance approach) were as old as 3,600 years. Microbial abundance, biomass, and activities (measured by direct counts, culture counts, total PLFAs, and radiorespirometry) declined with sediment age. The pattern is consistent with laboratory microcosm studies of Microbial survival: rapid short-term change followed by long-term survival of a proportion of cells. Even the oldest sediments evinced a small but viable Microbial community. Microbial survival appeared to be a function of sediment age. Porewater age appeared to influence the markup of surviving communities, as indicated by PLFA profiles. Sites with different Porewater recharge rates and patterns of Pleistocene flooding had different communities.

  3. Clinical and Genetic Modifiers of Long-term Survival in Heart Failure

    PubMed Central

    Cresci, Sharon; Kelly, Reagan J; Cappola, Thomas P; ScM; Diwan, Abhinav; Dries, Daniel; Kardia, Sharon LR; Dorn, Gerald W

    2009-01-01

    Objective To identify genetic modifiers of β-blocker (BB) response and long-term survival in heart failure (HF). Background Differences in BB treatment effect between Caucasians and African Americans with HF have been reported. Methods Prospective cohort study of 2,460 patients (711 African American; 1,749 Caucasian) enrolled between 1999 and 2007. 2039 (81.7%) were treated with BB. Each was genotyped for β1-adrenergic receptor (ADRB1) Arg389>Gly and G-protein receptor kinase 5 (GRK5) Gln41>Leu polymorphisms, which are more prevalent among African Americans than Caucasians. Primary endpoint was survival time from HF onset. Results There were 765 deaths during follow up (median 46 months). BB treatment increased survival in Caucasians (Log Rank P=0.00038) but not African Americans (Log Rank P=0.327). Among patients not taking BB, ADRB1 Gly389 was associated with decreased survival in Caucasians (HR = 1.98, 95% CI = 1.1 − 3.7, P = 0.03) while GRK5 Leu41 was associated with improved survival in African Americans (HR = 0.325, CI = 0.133 − 0.796, P = 0.01). ADRB1 Gly389 GRK5 Gln41Gln African Americans derived similar survival benefit from BB therapy (HR = 0.385 95% CI = 0.182 − 0.813, P = 0.012) as ADRB1 Gly389 GRK5 Gln41Gln Caucasians (HR = 0.529, 95% CI = 0.326 − 0.858, P=0.0098). Conclusions These data demonstrate that differences caused by β-adrenergic receptor signaling pathway gene polymorphisms, rather than race, are the major factors contributing to apparent differences in BB treatment effect between Caucasians and African Americans; proper evaluation of treatment response should account for genetic variance. PMID:19628119

  4. Long-Term Survival for Patients with Acute Decompensated Heart Failure According to Ejection Fraction Findings

    PubMed Central

    Coles, Andrew H.; Fisher, Kimberly; Darling, Chad; Yarzebski, Jorge; McManus, David D.; Gore, Joel M.; Lessard, Darleen; Goldberg, Robert J.

    2014-01-01

    Limited data exists about the long-term prognosis of patients with acute decompensated heart failure (ADHF) further stratified according to ejection fraction (EF) findings. The primary objective of this population-based observational study was to characterize and compare trends in long-term prognosis after an episode of ADHF across 3 EF strata. Hospital medical records were reviewed for 3,604 residents of the Worcester (MA) metropolitan area who were discharged after ADHF from all 11 medical centers in central Massachusetts during 1995, 2000, 2002, and 2004 and had EF measurements during their index hospitalization. The average age of this population was 75 years, the majority was white, and 44% were men. Approximately 49% of the population had preserved EF HF (HF-PEF) (≥50%), 37% had reduced EF HF (HF-REF) (<40%), and 14% had borderline EF HF (41-49%) (HF-BREF). Patients with HF-PEF experienced higher post discharge survival rates than patients with either HF-REF or HF-BREF at 1, 2, and 5-years after discharge from all central Massachusetts medical centers. While prognosis at 1-year after hospital discharge improved for all patient groups during the years under study, especially for those with HF-REF and HF-PEF, these encouraging trends declined with increasing duration of follow-up. In conclusion, although improvements in 1-year post-discharge survival were observed for patients in each of the 3 EF groups examined to varying degrees, the post-discharge prognosis of all patients with ADHF remains guarded. PMID:25092194

  5. Commercial kidney transplantation is an important risk factor in long-term kidney allograft survival.

    PubMed

    Prasad, G V Ramesh; Ananth, Sailesh; Palepu, Sneha; Huang, Michael; Nash, Michelle M; Zaltzman, Jeffrey S

    2016-05-01

    Transplant tourism, a form of transplant commercialization, has resulted in serious short-term adverse outcomes that explain reduced short-term kidney allograft survival. However, the nature of longer-term outcomes in commercial kidney transplant recipients is less clear. To study this further, we identified 69 Canadian commercial transplant recipients of 72 kidney allografts transplanted during 1998 to 2013 who reported to our transplant center for follow-up care. Their outcomes to 8 years post-transplant were compared with 702 domestic living donor and 827 deceased donor transplant recipients during this period using Kaplan-Meier survival plots and multivariate Cox regression analysis. Among many complications, notable specific events included hepatitis B or C seroconversion (7 patients), active hepatitis and/or fulminant hepatic failure (4 patients), pulmonary tuberculosis (2 patients), and a type A dissecting aortic aneurysm. Commercial transplantation was independently associated with significantly reduced death-censored kidney allograft survival (hazard ratio 3.69, 95% confidence interval 1.88-7.25) along with significantly delayed graft function and eGFR 30 ml/min/1.73 m(2) or less at 3 months post-transplant. Thus, commercial transplantation represents an important risk factor for long-term kidney allograft loss. Concerted arguments and efforts using adverse recipient outcomes among the main premises are still required in order to eradicate transplant commercialization.

  6. IL-7 receptor blockade following T cell depletion promotes long-term allograft survival

    PubMed Central

    Mai, Hoa-Le; Boeffard, Françoise; Longis, Julie; Danger, Richard; Martinet, Bernard; Haspot, Fabienne; Vanhove, Bernard; Brouard, Sophie; Soulillou, Jean-Paul

    2014-01-01

    T cell depletion is commonly used in organ transplantation for immunosuppression; however, a restoration of T cell homeostasis following depletion leads to increased memory T cells, which may promote transplant rejection. The cytokine IL-7 is important for controlling lymphopoiesis under both normal and lymphopenic conditions. Here, we investigated whether blocking IL-7 signaling with a mAb that targets IL-7 receptor α (IL-7Rα) alone or following T cell depletion confers an advantage for allograft survival in murine transplant models. We found that IL-7R blockade alone induced indefinite pancreatic islet allograft survival if anti–IL-7R treatment was started 3 weeks before graft. IL-7R blockade following anti-CD4– and anti-CD8–mediated T cell depletion markedly prolonged skin allograft survival. Furthermore, IL-7 inhibition in combination with T cell depletion synergized with either CTLA-4Ig administration or suboptimal doses of tacrolimus to induce long-term skin graft acceptance in this stringent transplant model. Together, these therapies inhibited T cell reconstitution, decreased memory T cell numbers, increased the relative frequency of Tregs, and abrogated both cellular and humoral alloimmune responses. Our data suggest that IL-7R blockade following T cell depletion has potential as a robust, immunosuppressive therapy in transplantation. PMID:24569454

  7. Elevated Omentin Serum Levels Predict Long-Term Survival in Critically Ill Patients

    PubMed Central

    Luedde, Mark; Benz, Fabian; Niedeggen, Jennifer; Vucur, Mihael; Hippe, Hans-Joerg; Spehlmann, Martina E.; Schueller, Florian; Loosen, Sven; Frey, Norbert; Trautwein, Christian; Koch, Alexander; Luedde, Tom; Tacke, Frank

    2016-01-01

    Introduction. Omentin, a recently described adipokine, was shown to be involved in the pathophysiology of inflammatory and infectious diseases. However, its role in critical illness and sepsis is currently unknown. Materials and Methods. Omentin serum concentrations were measured in 117 ICU-patients (84 with septic and 33 with nonseptic disease etiology) admitted to the medical ICU. Results were compared with 50 healthy controls. Results. Omentin serum levels of critically ill patients at admission to the ICU or after 72 hours of ICU treatment were similar compared to healthy controls. Moreover, circulating omentin levels were independent of sepsis and etiology of critical illness. Notably, serum concentrations of omentin could not be linked to concentrations of inflammatory cytokines or routinely used sepsis markers. While serum levels of omentin were not predictive for short term survival during ICU treatment, low omentin concentrations were an independent predictor of patients' overall survival. Omentin levels strongly correlated with that of other adipokines (e.g., leptin receptor or adiponectin), which have also been identified as prognostic markers in critical illness. Conclusions. Although circulating omentin levels did not differ between ICU-patients and controls, elevated omentin levels were predictive for an impaired patients' long term survival. PMID:27867249

  8. Clinical Score Predicting Long-Term Survival after Repeat Resection for Recurrent Adrenocortical Carcinoma

    PubMed Central

    Tran, Thuy B; Maithel, Shishir K; Pawlik, Timothy M; Wang, Tracy S; Hatzaras, Ioannis; Phay, John E; Fields, Ryan C; Weber, Sharon M; Sicklick, Jason K; Yopp, Adam C; Duh, Quan-Yang; Solorzano, Carmen C; Votanopoulos, Konstantinos I; Poultsides, George A

    2017-01-01

    BACKGROUND Adrenocortical carcinoma (ACC) is an aggressive malignancy typically resistant to chemotherapy and radiation. Surgery, even in the setting of locally recurrent or metastatic disease, remains the only potentially curative option. However, the subset of patients who will benefit from repeat resection in this setting remains ill defined. The objective of this study was to propose a prognostic clinical score that facilitates selection of patients for repeat resection of recurrent ACC. STUDY DESIGN Patients who underwent curative-intent repeat resection for recurrent ACC at 1 of 13 academic medical centers participating in the US ACC Study Group were identified. End points included morbidity, mortality, and overall survival. RESULTS Fifty-six patients underwent repeat curative-intent resection for recurrent ACC (representing 21% of 265 patients who underwent resection for primary ACC) from 1997 to 2014. Median age was 52 years. Sites of resected recurrence included locoregional only (54%), lung only (14%), liver only (12%), combined locoregional and lung (4%), combined liver and lung (4%), and other distant sites (12%). Thirty-day morbidity and mortality rates were 40% and 5.4%, respectively. Cox regression analysis revealed that the presence of multifocal recurrence, disease-free interval <12 months, and extrapulmonary distant metastases were independent predictors of poor survival. A clinical score consisting of 1-point each for the 3 variables demonstrated good discrimination in predicting survival after repeat resection (5-year: 72% for 0 points, 32% for 1 point, 0% for 2 or 3 points; p = 0.0006, area under the curve = 0.78). CONCLUSIONS Long-term survival after repeat resection for recurrent ACC is feasible when 2 of the following factors are present: solitary tumor, disease-free interval >12 months, and locoregional or pulmonary recurrence. PMID:27618748

  9. Long-term outcome after discontinuation of benzodiazepines for insomnia: a survival analysis of relapse.

    PubMed

    Morin, Charles M; Bélanger, Lynda; Bastien, Célyne; Vallières, Annie

    2005-01-01

    Discontinuation of benzodiazepine (BZD) treatment for insomnia can be a difficult task. Cognitive-behavior therapy (CBT) for insomnia, combined with a supervised medication taper, can facilitate withdrawal but there is limited evidence on long-term outcome after discontinuation. The objective of this study was to examine medication-free survival time and predictors of relapse (i.e., resumed BZD hypnotics) over a 2-year period in 47 older adults (mean age 62.1 years) with persistent insomnia and prolonged BZD use (average duration of 18.9 years), who had successfully discontinued BZD following CBT for insomnia, a supervised medication taper program, or a combined approach. The Kaplan-Meier product-limit method was used to estimate survival time, defined as time between end-of-treatment and relapse or end of follow-up. By the end of the 24-month follow-up, 42.6% of the samples had resumed BZD use. Participants in the Combined (33.3%) and Taper (30.8%) groups relapsed significantly less than their counterparts from the CBT group (69.2%). Survival rates at 3 months were 61.5% (CBT), 100% (Taper), and 80.9% (Combined). At 12 months, they were 38.5%, 83.3%, and 70.8%, respectively; and, at 24 months, they were 28.9%, 64.8% and 64.9%, respectively. Mean survival time was significantly longer for both the Taper (18.6 months, SE = 2.1) and Combined groups (12.6 months, SE = 1.4), relative to the CBT group (8.5 months, SE = 1.8). Significant predictors of relapse included treatment condition, end of treatment insomnia severity, and psychological distress. In conclusion, there is a substantial relapse rate following BZD discontinuation among prolonged users. CBT booster sessions might enhance compliance with CBT and prove useful in preventing relapse.

  10. Increased cortical surface area and gyrification following long-term survival from early monocular enucleation

    PubMed Central

    Kelly, Krista R.; DeSimone, Kevin D.; Gallie, Brenda L.; Steeves, Jennifer K.E.

    2014-01-01

    Purpose Retinoblastoma is typically diagnosed before 5 years of age and is often treated by enucleation (surgical removal) of the cancerous eye. Here, we sought to characterize morphological changes of the cortex following long-term survival from early monocular enucleation. Methods Nine adults with early right-eye enucleation (≤48 months of age) due to retinoblastoma were compared to 18 binocularly intact controls. Surface area, cortical thickness, and gyrification estimates were obtained from T1 weighted images and group differences were examined. Results Early monocular enucleation was associated with increased surface area and/or gyrification in visual (i.e., V1, inferior temporal), auditory (i.e., supramarginal), and multisensory (i.e., superior temporal, inferior parietal, superior parietal) cortices compared with controls. Visual cortex increases were restricted to the right hemisphere contralateral to the remaining eye, consistent with previous subcortical data showing asymmetrical lateral geniculate nucleus volume following early monocular enucleation. Conclusions Altered morphological development of visual, auditory, and multisensory regions occurs subsequent to long-time survival from early eye loss. PMID:25610793

  11. Antiglycation effects of carnosine and other compounds on the long-term survival of Escherichia coli.

    PubMed

    Pepper, Evan D; Farrell, Michael J; Nord, Gary; Finkel, Steven E

    2010-12-01

    Glycation, or nonenzymatic glycosylation, is a chemical reaction between reactive carbonyl-containing compounds and biomolecules containing free amino groups. Carbonyl-containing compounds include reducing sugars such as glucose or fructose, carbohydrate-derived compounds such as methylglyoxal and glyoxal, and nonsugars such as polyunsaturated fatty acids. The latter group includes molecules such as proteins, DNA, and amino lipids. Glycation-induced damage to these biomolecules has been shown to be a contributing factor in human disorders such as Alzheimer's disease, atherosclerosis, and cataracts and in diabetic complications. Glycation also affects Escherichia coli under standard laboratory conditions, leading to a decline in bacterial population density and long-term survival. Here we have shown that as E. coli aged in batch culture, the amount of carboxymethyl lysine, an advanced glycation end product, accumulated over time and that this accumulation was affected by the addition of glucose to the culture medium. The addition of excess glucose or methylglyoxal to the culture medium resulted in a dose-dependent loss of cell viability. We have also demonstrated that glyoxylase enzyme GloA plays a role in cell survival during glycation stress. In addition, we have provided evidence that carnosine, folic acid, and aminoguanidine inhibit glycation in prokaryotes. These agents may also prove to be beneficial to eukaryotes since the chemical processes of glycation are similar in these two domains of life.

  12. Long-Term Survival of Individuals Born Small and Large for Gestational Age

    PubMed Central

    Wennerström, E. Christina M.; Simonsen, Jacob; Melbye, Mads

    2015-01-01

    Background Little is known on long-term survival and causes of death among individuals born small or large for gestational age. This study investigates birth weight in relation to survival and causes of death over time. Methods A national cohort of 1.7 million live-born singletons in Denmark was followed during 1979–2011, using the Danish Civil Registration System, the Medical Birth Registry and the Cause of Death Registry. Cox proportional hazards were estimated for the impact of small (SGA) and large (LGA) gestation weight and mortality overall, by age group and birth cohort. Results Compared to normal weight children, SGA children were associated with increased risk of dying over time. Though most of the deaths occurred during the first year of life, the cumulative mortality risk was increased until 30 years of age. The hazard ratios [HR] for dying among SGA children ages <2 years were: 3.47 (95% CI, 3.30–3.64) and 1.06 (95% CI, 0.60–1.87) in 30 years and older. HR for dying among SGA adults (20–29 years) were: 1.20 (95% CI, 0.99–1.46) in years 1979–1982 and 1.61 (95% CI, 1.04–2.51) in years 1989–1994. The SGA born had increased risk of dying from infection, heart disease, respiratory disease, digestive disease, congenital malformation, perinatal conditions, and accidents, suicide, and homicide. Individuals born LGA were associated with decreased mortality risk, but with increased risk of dying from malignant neoplasm. Conclusions Survival has improved independently of birth weight the past 30 years. However, children born SGA remain at significantly increased risk of dying up till they turn 30 years of age. Individuals born LGA have lower mortality risk but only in the first two years of life. PMID:26390219

  13. Long-Term Survival of Hydrated Resting Eggs from Brachionus plicatilis

    PubMed Central

    Clark, Melody S.; Denekamp, Nadav Y.; Thorne, Michael A. S.; Reinhardt, Richard; Drungowski, Mario; Albrecht, Marcus W.; Klages, Sven; Beck, Alfred; Kube, Michael; Lubzens, Esther

    2012-01-01

    Background Several organisms display dormancy and developmental arrest at embryonic stages. Long-term survival in the dormant form is usually associated with desiccation, orthodox plant seeds and Artemia cysts being well documented examples. Several aquatic invertebrates display dormancy during embryonic development and survive for tens or even hundreds of years in a hydrated form, raising the question of whether survival in the non-desiccated form of embryonic development depends on pathways similar to those occurring in desiccation tolerant forms. Methodology/Principal Findings To address this question, Illumina short read sequencing was used to generate transcription profiles from the resting and amictic eggs of an aquatic invertebrate, the rotifer, Brachionus plicatilis. These two types of egg have very different life histories, with the dormant or diapausing resting eggs, the result of the sexual cycle and amictic eggs, the non-dormant products of the asexual cycle. Significant transcriptional differences were found between the two types of egg, with amictic eggs rich in genes involved in the morphological development into a juvenile rotifer. In contrast, representatives of classical “stress” proteins: a small heat shock protein, ferritin and Late Embryogenesis Abundant (LEA) proteins were identified in resting eggs. More importantly however, was the identification of transcripts for messenger ribonucleoprotein particles which stabilise RNA. These inhibit translation and provide a valuable source of useful RNAs which can be rapidly activated on the exit from dormancy. Apoptotic genes were also present. Although apoptosis is inconsistent with maintenance of prolonged dormancy, an altered apoptotic pathway has been proposed for Artemia, and this may be the case with the rotifer. Conclusions These data represent the first transcriptional profiling of molecular processes associated with dormancy in a non-desiccated form and indicate important similarities in

  14. Early Significant Tumor Volume Reduction After Radiosurgery in Brain Metastases From Renal Cell Carcinoma Results in Long-Term Survival

    SciTech Connect

    Kim, Wook Ha; Kim, Dong Gyu; Han, Jung Ho; Paek, Sun Ha; Chung, Hyun-Tai; Park, Chul-Kee; Kim, Chae-Yong; Kim, Yong Hwy; Kim, Jin Wook; Jung, Hee-Won

    2012-04-01

    Purpose: To retrospectively evaluate survival of patients with brain metastasis from renal cell carcinoma (RCC) after radiosurgery. Patients and Methods: Between 1998 and 2010, 46 patients were treated with radiosurgery, and the total number of lesions was 99. The mean age was 58.9 years (range, 33-78 years). Twenty-six patients (56.5%) had a single brain metastasis. The mean tumor volume was 3.0 cm{sup 3} (range, 0.01-35.1 cm{sup 3}), and the mean marginal dose prescribed was 20.8 Gy (range, 12-25 Gy) at the 50% isodose line. A patient was classified into the good-response group when the sum of the volume of the brain metastases decreased to less than 75% of the original volume at a 1-month follow-up evaluation using MRI. Results: As of December 28, 2010, 39 patients (84.8%) had died, and 7 (15.2%) survived. The overall median survival time was 10.0 {+-} 0.4 months (95% confidence interval, 9.1-10.8). After treatment, local tumor control was achieved in 72 (84.7%) of the 85 tumors assessed using MRI after radiosurgery. The good-response group survived significantly longer than the poor-response group (median survival times of 18.0 and 9.0 months, respectively; p = 0.025). In a multivariate analysis, classification in the good-response group was the only independent prognostic factor for longer survival (p = 0.037; hazard ratio = 0.447; 95% confidence interval, 0.209-0.953). Conclusions: Radiosurgery seems to be an effective treatment modality for patients with brain metastases from RCC. The early significant tumor volume reduction observed after radiosurgery seems to result in long-term survival in RCC patients with brain metastases.

  15. A Carboniferous non-onychophoran lobopodian reveals long-term survival of a Cambrian morphotype.

    PubMed

    Haug, Joachim T; Mayer, Georg; Haug, Carolin; Briggs, Derek E G

    2012-09-25

    Lobopodians, a nonmonophyletic assemblage of worm-shaped soft-bodied animals most closely related to arthropods, show two major morphotypes: long-legged and short-legged forms. The morphotype with stubby, conical legs has a long evolutionary history, from the early Cambrian through the Carboniferous, including the living onychophorans and tardigrades. Species with tubular lobopods exceeding the body diameter have been reported exclusively from the Cambrian; the three-dimensionally preserved Orstenotubulus evamuellerae from the uppermost middle Cambrian "Orsten" (Sweden) is the youngest long-legged lobopodian reported thus far. Here we describe a new long-legged lobopodian, Carbotubulus waloszeki gen. et sp. nov., from Mazon Creek, Illinois, USA (∼296 million years ago). This first post-Cambrian long-legged lobopodian extends the range of this morphotype by about 200 million years. The three-dimensionally preserved specimen differs significantly from the associated short-legged form Ilyodes inopinata, of which we also present new head details. The discovery of a Carboniferous long-legged lobopodian provides a more striking example of the long-term survival of Cambrian morphotypes than, for example, the occurrence of a Burgess Shale-type biota in the Ordovician of Morocco and dampens the effect of any major extinction of taxa at the end of the middle Cambrian.

  16. Activated mTORC1 promotes long-term cone survival in retinitis pigmentosa mice

    PubMed Central

    Venkatesh, Aditya; Ma, Shan; Le, Yun Z.; Hall, Michael N.; Rüegg, Markus A.; Punzo, Claudio

    2015-01-01

    Retinitis pigmentosa (RP) is an inherited photoreceptor degenerative disorder that results in blindness. The disease is often caused by mutations in genes that are specific to rod photoreceptors; however, blindness results from the secondary loss of cones by a still unknown mechanism. Here, we demonstrated that the mammalian target of rapamycin complex 1 (mTORC1) is required to slow the progression of cone death during disease and that constitutive activation of mTORC1 in cones is sufficient to maintain cone function and promote long-term cone survival. Activation of mTORC1 in cones enhanced glucose uptake, retention, and utilization, leading to increased levels of the key metabolite NADPH. Moreover, cone death was delayed in the absence of the NADPH-sensitive cell death protease caspase 2, supporting the contribution of reduced NADPH in promoting cone death. Constitutive activation of mTORC1 preserved cones in 2 mouse models of RP, suggesting that the secondary loss of cones is caused mainly by metabolic deficits and is independent of a specific rod-associated mutation. Together, the results of this study address a longstanding question in the field and suggest that activating mTORC1 in cones has therapeutic potential to prolong vision in RP. PMID:25798619

  17. Spiritually Based Resources in Adaptation to Long-Term Prostate Cancer Survival: Perspectives of Elderly Wives

    ERIC Educational Resources Information Center

    Ka'opua, Lana Sue I.; Gotay, Carolyn C.; Boehm, Patricia S.

    2007-01-01

    Spiritually based resources (SBR) generally have a salutary effect on coping with cancer diagnosis and treatment. Few studies address this relationship in long-term cancer survivorship, however. As part of a study on long-term prostate cancer survivorship, wives' ways of coping with cancer-related issues were explored through longitudinal…

  18. Long-term survival and germination of Bacillus thuringiensis var. kurstaki in a field trial.

    PubMed

    Hendriksen, Niels Bohse; Hansen, Bjarne Munk

    2002-03-01

    Long-term survival, dispersal, and germination of Bacillus thuringiensis var. kurstaki DMU67R has been investigated in a field trial. An experimental cabbage plot was sprayed with DMU67R in 1993 and allowed to lie fallow since. The investigations reported here were carried out from 1997 to 2000 in this plot. High persistence of DMU67R for 7 years in the bulk soil of the plot has been demonstrated. The numbers have not significantly reduced since 1994, stabilizing around 6.6 x 10(2) cfu/g from 1996 to 2000. Horizontal dispersal of DMU67R in the 1994-1999 period was limited. Vertical dispersal occurred from 1994 to 1999, as 77% of the population of DMU67R occurred in the 0-2 cm layer in 1994, while only 22% of the population was found there in 1999. Most of the population in 1999 was present homogeneously in the upper 6 cm of the soil profile. Germination, as evidenced by the ratio of DMU67R cfu before and after heat treatment, was not observed in the bulk soil. However, in the rhizospheres of dandelion (Taraxacum officinalis) and quackgrass (Agropyron repens), 40 and 50% of DMU67R was present as vegetative germinated cells, respectively. No germination occurred in the rhizosphere of red fescue (Festuca rubra). The material from the gut of the earthworm species Lumbricus rubellus, Lumbricus terrestris, and Apporrectodea caliginosa and from a tipulid larvae from the plot also contained vegetative cells of DMU67R. Further investigations of A. caliginosa showed that germination seemed to be restricted to the gut and that sporulation occurred after defecation. The germination of DMU67R in rhizospheres and in the gut of nontarget invertebrates suggests that survival in the soil of B. thuringiensis is a dynamic process involving germination, cell divisions, and sporulation in specific microhabitats.

  19. Long-Term Survival of Fecal Indicator Bacteria in Estuarine Sediment

    NASA Astrophysics Data System (ADS)

    Ferguson, A. S.; Layton, A.; Culligan, P. J.; Kenna, T. C.; Mailloux, B. J.

    2010-12-01

    Fecal contamination of marine and freshwater environments can negatively impact water quality, leading to contaminated drinking water as well as the closure of recreational beaches and waterways. Fecal contamination is routinely assessed using fecal indicator bacteria (FIB), and even though the potential for their long-term survival or proliferation in sediments exist, information linking deposition of FIB with sediment age is scarce. We evaluate sediments as a reservoir for culturable FIB, by examining dated sediments from the lower Hudson River estuary for Escherichia coli (E. coli), enterococcus, and Bacteroides. Sediment cores were collected from in the vicinity of the George Washington (GWB) and Tappan Zee (TZB) Bridges NY. Sediment deposition ages were constrained using gamma emitting radionuclides and pollution chronology. Culturable E. coli and enterococcus were quantified using a culture-based most probable number method (ColilertTM, Idexx Laboratories). Molecular based methods were used to quantify E. coli and Bacteroides. In the GWB core, viable enterococcus or E. coli were consistently detected in sediment younger than the 1960s with maximum concentrations of 39 and 171 cells/g, respectively. In the TZB core, only enterococcus was sporadically detected in sediment younger than 1950 with a maximum concentration of 79 cells/g. Molecular Bacteroides and E. coli were detected in all core samples with a geometric mean of 4.2x104 and 1.2x105 copies/g, respectively. Results indicate that fecal bacteria can survive within estuarine sediments for decades, suggesting that sediments could be a significant and persistent source of bacterial pollution.

  20. Realising the Real Benefits of Outsourcing: Measurement Excellence and Its Importance in Achieving Long Term Value

    NASA Astrophysics Data System (ADS)

    Oshri, Ilan; Kotlarsky, Julia

    These days firms are, more than ever, pressed to demonstrate returns on their investment in outsourcing. While the initial returns can always be associated with one-off cost cutting, outsourcing arrangements are complex, often involving inter-related high-value activities, which makes the realisation of long-term benefits from outsourcing ever more challenging. Executives in client firms are no longer satisfied with the same level of service delivery through the outsourcing lifecycle. They seek to achieve business transformation and innovation in their present and future services, beyond satisfying service level agreements (SLAs). Clearly the business world is facing a new challenge: an outsourcing delivery system of high-value activities that demonstrates value over time and across business functions. However, despite such expectations, many client firms are in the dark when trying to measure and quantify the return on outsourcing investments: results of this research show that less than half of all CIOs and CFOs (43%) have attempted to calculate the financial impact of outsourcing to their bottom line, indicating that the financial benefits are difficult to quantify (51%).

  1. A metabolic strategy to enhance long-term survival by Phx1 through stationary phase-specific pyruvate decarboxylases in fission yeast.

    PubMed

    Kim, Ji-Yoon; Kim, Eun-Jung; Lopez-Maury, Luis; Bähler, Jürg; Roe, Jung-Hye

    2014-07-01

    In the fission yeast Schizosaccharomyces pombe, the stationary phase-specific transcription factor Phx1 contributes to long-term survival, stress tolerance, and meiosis. We identified Phx1-dependent genes through transcriptome analysis, and further analyzed those related with carbohydrate and thiamine metabolism, whose expression decreased in ∆phx1. Consistent with mRNA changes, the level of thiamine pyrophosphate (TPP) and TPP-utilizing pyruvate decarboxylase activity that converts pyruvate to acetaldehyde were also reduced in the mutant. Therefore, Phx1 appears to shift metabolic flux by diverting pyruvate from the TCA cycle and respiration to ethanol fermentation. Among the four predicted genes for pyruvate decarboxylase, only the Phx1-dependent genes (pdc201+ and pdc202+) contributed to long-term survival as judged by mutation and overexpression studies. These findings indicate that the Phx1-mediated long-term survival is achieved primarily through increasing the synthesis and activity of pyruvate decarboxylase. Consistent with this hypothesis, we observed that Phx1 curtailed respiration when cells entered stationary phase. Introduction of Δphx1 mutation compromised the long-lived phenotypes of Δpka1 and Δsck2 mutants that are devoid of pro-aging kinases of nutrient-signalling pathways, and of the Δpyp1 mutant with constitutively activated stress-responsive kinase Sty1. Therefore, achievement of long-term viability through both nutrient limitation and anti-stress response appears to be dependent on Phx1.

  2. HLA-E expression in cervical adenocarcinomas: association with improved long-term survival

    PubMed Central

    2012-01-01

    Background Cervical cancer is the third most common cancer in women worldwide. The most common histopathological subtype is cervical squamous cell carcinoma (SCC, 75-80%), followed by adenocarcinoma (AC) and adenosquamous carcinoma (ASC; together 15-20%). Rising incidence rates of AC have been observed relative and absolute to SCC and evidence is accumulating that cervical AC is a distinct clinical entity. Cervical SCC, ASC, and AC are caused by a persistent infection with high-risk human papillomavirus (HPV) and failed control of the immune system plays a pivotal role in the carcinogenesis of all three histopathological subtypes. Human leukocyte antigen E (HLA-E), a non-classical HLA class Ib molecule, plays an important role in immune surveillance and immune escape of virally infected cells. In this study we investigated HLA-E expression in three well-defined cohorts of cervical AC, ASC, and SCC patients, and determined whether HLA-E expression was associated with histopathological parameters and patient survival. Methods and results HLA-E expression was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections of 79 SCC, 38 ASC, and 75 AC patients. All patients included were International Federation of Gynaecology and Obstetrics stage I-II and underwent radical hysterectomy with lymphadenectomy as primary treatment. Significant differences between the histopathological subgroups were detected for age distribution, HPV positivity, HPV type distribution, tumour size, tumour infiltration depth, lymph-vascular space invasion, and adjuvant radiotherapy. High expression of HLA-E was found in 107/192 (56%) cervical carcinomas, with significantly more overexpression in cervical AC compared to SCC and ASC (37/79 SCC, 18/38 ASC, and 52/75 AC; P = 0.010). High HLA-E expression in cervical AC was associated with favourable long term disease-specific and recurrence-free survival (P = 0.005 and P = 0.001, respectively). Conclusion

  3. Survival of a very low-birthweight infant with Potter sequence on long-term hemodialysis.

    PubMed

    Miyahara, Jun; Yamamoto, Masaki; Motoshige, Kyoko; Fujita, Naoya; Ohki, Shigeru

    2016-07-01

    Recent advances in neonatal cardiorespiratory management and neonatal renal replacement therapy have led to occasional reports of favorable short-term and long-term outcomes for Potter sequence, once thought to be fatal. The present patient was a girl born at a gestational age of 34 weeks 4 days with a birthweight of 1398 g. She was diagnosed with Potter sequence complicated by pulmonary hypoplasia due to left renal agenesis and small right kidney. Hemodialysis was started because anuria persisted even after persistent pulmonary hypertension receded and cardiorespiratory status improved. Peritoneal dialysis during the clinical course failed to achieve stability because of pericatheter leakage and frequent obstruction of the peritoneal dialysis catheter; in the meantime, hemodialysis was also performed. Once bodyweight passed 3.5 kg, peritoneal dialysis became more feasible with stability; the patient was discharged at 9 months and at the time of writing was on peritoneal dialysis at home, and renal transplantation was planned.

  4. Long term, continuous exposure to panobinostat induces terminal differentiation and long term survival in the TH-MYCN neuroblastoma mouse model.

    PubMed

    Waldeck, Kelly; Cullinane, Carleen; Ardley, Kerry; Shortt, Jake; Martin, Ben; Tothill, Richard W; Li, Jason; Johnstone, Ricky W; McArthur, Grant A; Hicks, Rodney J; Wood, Paul J

    2016-07-01

    Neuroblastoma is the most common extra-cranial malignancy in childhood and accounts for ∼15% of childhood cancer deaths. Amplification of MYCN in neuroblastoma is associated with aggressive disease and predicts for poor prognosis. Novel therapeutic approaches are therefore essential to improving patient outcomes in this setting. The histone deacetylases are known to interact with N-Myc and regulate numerous cellular processes via epigenetic modulation, including differentiation. In this study, we used the TH-MYCN mouse model of neuroblastoma to investigate the antitumor activity of the pan-HDAC inhibitor, panobinostat. In particular we sought to explore the impact of long term, continuous panobinostat exposure on the epigenetically driven differentiation process. Continuous treatment of tumor bearing TH-MYCN transgenic mice with panobinostat for nine weeks led to a significant improvement in survival as compared with mice treated with panobinostat for a three-week period. Panobinostat induced rapid tumor regression with no regrowth observed following a nine-week treatment period. Initial tumor response was associated with apoptosis mediated via upregulation of BMF and BIM. The process of terminal differentiation of neuroblastoma into benign ganglioneuroma, with a characteristic increase in S100 expression and reduction of N-Myc expression, occurred following prolonged exposure to the drug. RNA-sequencing analysis of tumors from treated animals confirmed significant upregulation of gene pathways associated with apoptosis and differentiation. Together our data demonstrate the potential of panobinostat as a novel therapeutic strategy for high-risk neuroblastoma patients.

  5. Long-Term Effects of Outpatient Geriatric Evaluation and Management on Health Care Utilization, Cost, and Survival

    ERIC Educational Resources Information Center

    Engelhardt, Joseph B.; Toseland, Ronald W.; Gao, Jian; Banks, Steven

    2006-01-01

    Purpose: The long-term effectiveness and efficiency of an outpatient geriatric evaluation and management (GEM) program was compared to usual primary care (UPC). Design and Method: A randomized controlled group design was used. Health care utilization, cost of care, and survival were assessed during a 48-month period among a sample of 160 male…

  6. Adaptation to Long-Term Prostate Cancer Survival: The Perspective of Elderly Asian/Pacific Islander Wives

    ERIC Educational Resources Information Center

    Ka'opua, Lana Sue I.; Gotay, Carolyn C.; Hannum, Meghan; Bunghanoy, Grace

    2005-01-01

    Increasingly evident is the important role of partners in patients' adaptation to diagnosis, treatment, and recovery. Yet, little is known about partners' adaptation when patients reach the benchmark known as long-term survival. This study describes elderly wives of prostate cancer survivors' perspectives of adaptation to the enduring challenges…

  7. Similar long-term survival of consecutive in-hospital and out-of-hospital cardiac arrest patients treated with targeted temperature management

    PubMed Central

    Engsig, Magaly; Søholm, Helle; Folke, Fredrik; Gadegaard, Peter J; Wiis, Julie Therese; Molin, Rune; Mohr, Thomas; Engsig, Frederik N

    2016-01-01

    Objective The long-term survival of in-hospital cardiac arrest (IHCA) patients treated with targeted temperature management (TTM) is poorly described. The aim of this study was to compare the outcomes of consecutive IHCA with out-of-hospital cardiac arrest (OHCA) patients treated with TTM. Design, setting, and patients Retrospectively collected data on all consecutive adult patients treated with TTM at a university tertiary heart center between 2005 and 2011 were analyzed. Measurements Primary endpoints were survival to hospital discharge and long-term survival. Secondary endpoint was neurological outcome assessed using the Pittsburgh cerebral performance category (CPC). Results A total of 282 patients were included in this study; 233 (83%) OHCA and 49 (17%) IHCA. The IHCA group presented more often with asystole, received bystander cardiopulmonary resuscitation (CPR) in all cases, and had shorter time to return of spontaneous circulation (ROSC). Survival to hospital discharge was 54% for OHCA and 53% for IHCA (adjusted odds ratio 0.98 [95% confidence interval {CI}; 0.43–2.24]). Age ≤60 years, bystander CPR, time to ROSC ≤10 min, and shockable rhythm at presentation were associated with survival to hospital discharge. Good neurologic outcome among survivors was achieved by 86% of OHCA and 92% of IHCA (P=0.83). After a median follow-up time of >5 years, 83% of OHCA and 77% of IHCA were alive (adjusted hazard ratio [HR] 1.51 [95% CI; 0.59–3.91]). Age ≤60 years was the only factor associated with long-term survival (adjusted HR 2.73 [95% CI; 1.36–5.52]). Conclusion There was no difference in short- and long-term survival and no difference in neurologic outcome to hospital discharge between IHCA and OHCA patients treated with TTM despite higher frequency of asystole in IHCA. PMID:27877067

  8. Incidence of Perioperative Complications Following Resection of Adrenocortical Carcinoma and Its Association with Long-Term Survival

    PubMed Central

    Kim, Yuhree; Tran, Thuy B.; Postlewait, Lauren M.; Maithel, Shishir K.; Wang, Tracy S.; Evans, Douglas B.; Hatzaras, Ioannis; Shenoy, Rivfka; Phay, John E.; Keplinger, Kara; Fields, Ryan C.; Moses, Lindsey E.; Weber, Sharon M.; Salem, Ahmed; Sicklick, Jason K.; Gad, Shady; Yopp, Adam C.; Mansour, John C.; Duh, Quan-Yang; Seiser, Natalie; Solorzano, Carmen C.; Kiernan, Colleen M.; Votanopoulos, Konstantinos I.; Levine, Edward A.; Poultsides, George A.; Pawlik, Timothy M.

    2016-01-01

    Background The association of postoperative complications with long-term oncologic outcomes remains unclear. We sought to determine the incidence of complications among patients who underwent surgery for adrenocortical carcinoma (ACC) and define the relationship of morbidity with long-term survival. Methods Patients who underwent surgery for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the US ACC group study. The incidence and type of the postoperative complications, the factors associated with them as well their association with long-term survival were analyzed. Results A total of 265 patients with median age of 52 years (IQR 44–63) were identified; at surgery, the majority of patients underwent an open abdominal procedure (n = 169, 66.8 %). A postoperative complication occurred in 99 patients for a morbidity of 37.4 %; five patients (1.9 %) died in hospital. Factors associated with morbidity included a thoraco-abdominal operative approach (reference: open abdominal; OR 2.85, 95 % CI 1.00–8.18), and a hormonally functional tumor (OR 3.56, 95 % CI 1.65–7.69) (all P < 0.05). Presence of any complication was associated with a worse long-term outcome (median survival: no complication, 58.9 months vs. any complication, 25.1 months; P = 0.009). In multivariate analysis, after adjusting for patient- and disease-related factors postoperative infectious complications independently predicted shorter overall survival (hazard ratio (HR) 5.56, 95 % CI 2.24–13.80; P < 0.001). Conclusion Postoperative complications were independently associated with decreased long-term survival after resection for ACC. The prevention of complications may be important from an oncologic perspective. PMID:26546184

  9. Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry.

    PubMed

    Pessoa de Magalhães, Roberto J; Vidriales, María-Belén; Paiva, Bruno; Fernandez-Gimenez, Carlos; García-Sanz, Ramón; Mateos, Maria-Victoria; Gutierrez, Norma C; Lecrevisse, Quentin; Blanco, Juan F; Hernández, Jose; de las Heras, Natalia; Martinez-Lopez, Joaquin; Roig, Monica; Costa, Elaine Sobral; Ocio, Enrique M; Perez-Andres, Martin; Maiolino, Angelo; Nucci, Marcio; De La Rubia, Javier; Lahuerta, Juan-Jose; San-Miguel, Jesús F; Orfao, Alberto

    2013-01-01

    Multiple myeloma remains largely incurable. However, a few patients experience more than 10 years of relapse-free survival and can be considered as operationally cured. Interestingly, long-term disease control in multiple myeloma is not restricted to patients with a complete response, since some patients revert to having a profile of monoclonal gammopathy of undetermined significance. We compared the distribution of multiple compartments of lymphocytes and dendritic cells in the bone marrow and peripheral blood of multiple myeloma patients with long-term disease control (n=28), patients with newly diagnosed monoclonal gammopathy of undetermined significance (n=23), patients with symptomatic multiple myeloma (n=23), and age-matched healthy adults (n=10). Similarly to the patients with monoclonal gammopathy of undetermined significance and symptomatic multiple myeloma, patients with long-term disease control showed an expansion of cytotoxic CD8(+) T cells and natural killer cells. However, the numbers of bone marrow T-regulatory cells were lower in patients with long-term disease control than in those with symptomatic multiple myeloma. It is noteworthy that B cells were depleted in patients with monoclonal gammopathy of undetermined significance and in those with symptomatic multiple myeloma, but recovered in both the bone marrow and peripheral blood of patients with long-term disease control, due to an increase in normal bone marrow B-cell precursors and plasma cells, as well as pre-germinal center peripheral blood B cells. The number of bone marrow dendritic cells and tissue macrophages differed significantly between patients with long-term disease control and those with symptomatic multiple myeloma, with a trend to cell count recovering in the former group of patients towards levels similar to those found in healthy adults. In summary, our results indicate that multiple myeloma patients with long-term disease control have a constellation of unique immune changes

  10. Learner-Centered Inquiry in Undergraduate Biology: Positive Relationships with Long-Term Student Achievement

    ERIC Educational Resources Information Center

    Derting, Terry L.; Ebert-May, Diane

    2010-01-01

    We determined short- and long-term correlates of a revised introductory biology curriculum on understanding of biology as a process of inquiry and learning of content. In the original curriculum students completed two traditional lecture-based introductory courses. In the revised curriculum students completed two new learner-centered,…

  11. Focusing on Short-Term Achievement Gains Fails to Produce Long-Term Gains

    ERIC Educational Resources Information Center

    Grissmer, David W.; Ober, David R.; Beekman, John A.

    2014-01-01

    The short-term emphasis engendered by No Child Left Behind (NCLB) has focused research predominantly on unraveling the complexities and uncertainties in assessing short-term results, rather than developing methods and assessing results over the longer term. In this paper we focus on estimating long-term gains and address questions important to…

  12. Preterm Birth, Age at School Entry and Long Term Educational Achievement

    PubMed Central

    Odd, David; Evans, David; Emond, Alan

    2016-01-01

    Objective To investigate if the detrimental impact of year of entering education in preterm infants persists into adolescence. Background Preterm infants are often enrolled in school a year earlier than would be expected if this decision is based on their actual date of birth rather than their due date. Initially these infants appear to do disproportionately worse than those who do not ‘skip’ a year. However, it is unclear if this effect remains as the infants grow, to have an important effect on long term achievements in education. Design A cohort study, drawn from the Avon Longitudinal Study of Parents and Children (ALSPAC). The exposure measurement was gestational age (defined as preterm (<37 weeks gestation) or term (37–42 weeks)). The primary outcome was a low score at the Key Stage 4 (KS4) educational assessment or receiving special educational needs support (both at age 16). We derived conditional regression models matching preterm to term infants on their date of birth (DOB), their expected date of delivery (EDD), or their expected date of delivery and year of school entry. Results After matching for DOB, preterm infants had an increased odds of SEN (OR 1.57 (1.33–1.86)) and the association remained after adjusting for potential confounders (OR 1.39 (1.14–1.68)). The association remained in the analysis matching for EDD (fully adjusted OR 1.43 (1.17–1.74)) but attenuated after restricting to those infants who were enrolled in school in the same year as the control infants (fully adjusted OR 1.21 (0.97–1.52)). There was less evidence for an impact of prematurity on the KS4 score (Matched for DOB; OR 1.10 (0.91 to 1.34), matched for EDD OR 1.17 (0.96 to 1.42) and EDD and same year of schooling, OR 1.00 (0.80 to 1.26)). Conclusions This modifiable effect of going to school a year earlier than predicted by their due date appears to have measurable consequences for ex-preterm infants in adolescence and is likely to limit adulthood opportunities

  13. Vena caval involvement by renal cell carcinoma. Surgical resection provides meaningful long-term survival.

    PubMed Central

    Skinner, D G; Pritchett, T R; Lieskovsky, G; Boyd, S D; Stiles, Q R

    1989-01-01

    In 1972 we first reported that vena caval extension by tumor thrombus was a potentially curable lesion provided that complete removal could be achieved. We have developed a technique for safe removal of extensive vena caval thrombi extending up to the right atrium without the need for cardiopulmonary bypass or hypothermic cardioplegia. Cardiopulmonary bypass, however, is advocated for some type III thrombi, but the addition of the pump and heparinization compounds the magnitude of the procedure. We use a right thoracoabdominal approach for tumors arising from either kidney with vascular isolation of the vena cava from its insertion into the right atrium to the iliac bifurcation. From 1972 to 1988, 56 patients ranging in age from 31 to 76 years were evaluated and 53 underwent radical nephrectomy with en bloc vena caval tumor thrombectomy. Of these patients, 21 had subhepatic caval thrombus extension (level 1); 24 had extension into the intrahepatic vena cava (level 2), and 8 had thrombi extending into the heart (level 3). Overall 1-, 3-, and 5-year survival was 56%, 34%, and 25%, respectively. Crucial to survival was complete surgical excision. Successful extirpation of all apparent tumor was possible in 75% of the patients in this series. With an expected 5-year survival rate of 57% for those without metastatic disease to other organs, we continue to advocate an aggressive optimistic approach for patients if there is no preoperative evidence of metastatic disease. Images Fig. 1. Fig. 2. Fig. 3. PMID:2774709

  14. Predictors of long-term survival among first-ever ischemic and hemorrhagic stroke in a Brazilian stroke cohort

    PubMed Central

    2013-01-01

    Background Few studies have examined both ischemic and hemorrhagic stroke to identify prognostic factors associated to long-term stroke survival. We investigated long-term survival and predictors that could adversely influence ischemic and hemorrhagic first-ever stroke prognosis. Methods We prospectively ascertained 665 consecutive first-ever ischemic and hemorrhagic stroke cases from “The Study of Stroke Mortality and Morbidity” (The EMMA Study) in a community hospital in São Paulo, Brazil. We evaluated cardiovascular risk factors and sociodemographic characteristics (age, gender, race and educational level). Results We found a lower survival rate among hemorrhagic cases compared to ischemic stroke cases at the end of 4 years of follow-up (52% vs. 44%, p = 0.04). The risk of death was two times higher among people with ischemic stroke without formal education. Also, we found consistently higher risk of death for diabetics with ischemic stroke (HR = 1.45; 95% CI = 1.07-1.97) compared to no diabetics. As expected, age equally influenced on the high risk of poor survival, regardless of stroke subtype. Conclusions For ischemic stroke, the lack of formal education and diabetes were significant independent predictors of poor long-term survival. PMID:23706067

  15. Surviving the Holocaust: A Meta-Analysis of the Long-Term Sequelae of a Genocide

    ERIC Educational Resources Information Center

    Barel, Efrat; Van Ijzendoorn, Marinus H.; Sagi-Schwartz, Abraham; Bakermans-Kranenburg, Marian J.

    2010-01-01

    The current set of meta-analyses elucidates the long-term psychiatric, psychosocial, and physical consequences of the Holocaust for survivors. In 71 samples with 12,746 participants Holocaust survivors were compared with their counterparts (with no Holocaust background) on physical health, psychological well-being, posttraumatic stress symptoms,…

  16. Supercooling enables long-term transplantation survival following 4 days of liver preservation.

    PubMed

    Berendsen, Tim A; Bruinsma, Bote G; Puts, Catheleyne F; Saeidi, Nima; Usta, O Berk; Uygun, Basak E; Izamis, Maria-Louisa; Toner, Mehmet; Yarmush, Martin L; Uygun, Korkut

    2014-07-01

    The realization of long-term human organ preservation will have groundbreaking effects on the current practice of transplantation. Herein we present a new technique based on subzero nonfreezing preservation and extracorporeal machine perfusion that allows transplantation of rat livers preserved for up to four days, thereby tripling the viable preservation duration.

  17. Predicting Long-Term Growth in Students' Mathematics Achievement: The Unique Contributions of Motivation and Cognitive Strategies

    ERIC Educational Resources Information Center

    Murayama, Kou; Pekrun, Reinhard; Lichtenfeld, Stephanie; vom Hofe, Rudolf

    2013-01-01

    This research examined how motivation (perceived control, intrinsic motivation, and extrinsic motivation), cognitive learning strategies (deep and surface strategies), and intelligence jointly predict long-term growth in students' mathematics achievement over 5 years. Using longitudinal data from six annual waves (Grades 5 through 10;…

  18. Positive effects of growth at suboptimal temperature and high salt concentration on long-term survival of Lactobacillus sakei.

    PubMed

    Marceau, Anika; Zagorec, Monique; Champomier-Vergès, Marie Christine

    2003-01-01

    Lactobacillus sakei is a lactic acid bacterium commonly found on fresh meat and represents the predominant flora of vacuum-packed meat. In the present article, we studied the behavior of L. sakei in a chemically defined medium under various growth conditions relative to temperature or NaCl concentration. Growth occurred at each temperature, but growth rate and final cell density decreased at low temperature and survival was enhanced. In the presence of NaCl, we also observed a longer doubling time and a lower final cell density together with an enhanced long-term survival. When both conditions were combined, the long-term survival was greatly increased to about 28 weeks. Differences in cell morphology were observed under electron microscopy when cells were grown at low temperature in the presence of salt. We speculate that these are due to modifications in membrane structure. These results show that L. sakei is able to adapt to these environmental conditions and that slow growth is clearly associated with enhanced long-term survival.

  19. Early response to neoadjuvant chemotherapy can help predict long-term survival in patients with cervical cancer

    PubMed Central

    Shen, Jian; Zhou, Hang; Yang, Runfeng; Wang, Lin; Liu, Jiong; Zhang, Jincheng; Sun, Haiying; Jia, Yao; Du, Xiaofang; Wang, Haoran; Deng, Song; Ding, Ting; Jiang, Jingjing; Lu, Yunping; Li, Shuang; Wang, Shixuan; Ma, Ding

    2016-01-01

    It is still controversial whether cervical cancer patients with clinical responses after neoadjuvant chemotherapy (NACT) have a better long-term survival or not. This study was designed to investigate the effect of the clinical response on the disease-free survival (DFS) of cervical cancer patients undergoing NACT. A total of 853 patients from a retrospective study were used to evaluate whether the clinical response was an indicator for the long-term response, and 493 patients from a prospective cohort study were used for further evaluation. The survival difference was detected by log-rank test, univariate and multivariate Cox regression and a pooled analysis. The log-rank test revealed that compared with non-responders, the DFS of responders was significantly higher in the retrospective data (P = 0.007). Univariate Cox regression showed that the clinical response was an indicator of long-term survival in the retrospective study (HR 1.83, 95% CI 1.18-2.85, P = 0.007). In a multivariate Cox model, the clinical response was still retained as an independent significant prognostic factor in the retrospective study (HR 1.59, 95% CI 1.01-2.50, P = 0.046). The result was also validated in the prospective data with similar results. These findings implied that the clinical response can be regarded as an independent predictor of DFS. PMID:27557523

  20. Insights into the molecular basis of long-term storage and survival of sperm in the honeybee (Apis mellifera)

    PubMed Central

    Paynter, Ellen; Millar, A. Harvey; Welch, Mat; Baer-Imhoof, Barbara; Cao, Danyang; Baer, Boris

    2017-01-01

    Honeybee males produce ejaculates consisting of large numbers of high quality sperm. Because queens never re-mate after a single mating episode early in life, sperm are stored in a specialised organ for years but the proximate mechanisms underlying this key physiological adaptation are unknown. We quantified energy metabolism in honeybee sperm and show that the glycolytic metabolite glyceraldehyde-3-phosphate (GA3P) is a key substrate for honeybee sperm survival and energy production. This reliance on non-aerobic energy metabolism in stored sperm was further supported by our findings of very low levels of oxygen inside the spermatheca. Expression of GA3P dehydrogenase (GAPDH), the enzyme involved in catabolism of GA3P, was significantly higher in stored compared to ejaculated sperm. Therefore, long-term sperm storage seems facilitated by the maintenance of non-aerobic energy production, the need for only the ATP-producing steps of glycolysis and by avoiding sperm damage resulting from ROS production. We also confirm that honeybee sperm is capable of aerobic metabolism, which predominates in ejaculated sperm while they compete for access to the spermatheca, but is suppressed during storage. Consequently, the remarkable reproductive traits of honeybees are proximately achieved by differential usage of energy production pathways to maximise competitiveness and minimise damage of sperm. PMID:28091518

  1. [Psychosocial impact of breast cancer in long-term survival: proposal of an integral follow-up care for survivors].

    PubMed

    Vivar, Cristina G

    2012-05-01

    The aim of the article is to show the psychosocial impact of breast cancer in the long-term survival and to promote the idea of implementing a follow-up plan for survivors. A narrative review of published articles on the experience of survival in breast cancer survivors was conducted. Data were organised according to the domains of measurement (physical, psychological and social) of the Quality of Life of Long-term Breast Cancer Survivors Scale (LTQOL-BC). Breast cancer survivors may feel emotionally affected by the physical sequels (mastectomy, lymphedema, early menopause, and infertility), psychological (fear of recurrence and emotional stress) and/or social (family relationships and employment changes). The data are the foundation of a proposal of specific follow-up care for breast cancer survivors.

  2. Long-term survival in glioblastoma: methyl guanine methyl transferase (MGMT) promoter methylation as independent favourable prognostic factor

    PubMed Central

    Smrdel, Uros; Zwitter, Matjaz; Bostjancic, Emanuela; Zupan, Andrej; Kovac, Viljem; Glavac, Damjan; Bokal, Drago; Jerebic, Janja

    2016-01-01

    Abstract Background In spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical prognostic factors (age, gender, extent of surgery and performance status) do not clearly predict long-term survival. The aim of this case-control study was to evaluate immuno-histochemical and genetic characteristics of the tumour as additional prognostic factors in glioblastoma. Patients and methods Long-term survivor group were 40 patients with glioblastoma with survival longer than 30 months. Control group were 40 patients with shorter survival and matched to the long-term survivor group according to the clinical prognostic factors. All patients underwent multimodality treatment with surgery, postoperative conformal radiotherapy and temozolomide during and after radiotherapy. Biopsy samples were tested for the methylation of MGMT promoter (with methylation specific polymerase chain reaction), IDH1 (with immunohistochemistry), IDH2, CDKN2A and CDKN2B (with multiplex ligation-dependent probe amplification), and 1p and 19q mutations (with fluorescent in situ hybridization). Results Methylation of MGMT promoter was found in 95% and in 36% in the long-term survivor and control groups, respectively (p < 0.001). IDH1 R132H mutated patients had a non-significant lower risk of dying from glioblastoma (p = 0.437), in comparison to patients without this mutation. Other mutations were rare, with no significant difference between the two groups. Conclusions Molecular and genetic testing offers additional prognostic and predictive information for patients with glioblastoma. The most important finding of our analysis is that in the absence of MGMT promoter methylation, longterm survival is very rare. For patients without this mutation, alternative treatments should be explored. PMID:27904447

  3. Long-term management strategies to achieve optimal function in patients with bipolar disorder.

    PubMed

    Keck, Paul E

    2006-01-01

    Functional impairment is a problem for people with bipolar disorder. Predictors of poor functional outcome are psychiatric and medical comorbidity, interepisode subsyndromal symptoms, psychosis during a manic or mixed episode, and low premorbid functioning. Cognitive dysfunction may also be a contributory factor in functional impairment. Several psychosocial interventions designed for people with bipolar disorder have demonstrated success in improving syndromal outcomes, but the effects of psychosocial interventions on functioning and cognition have not been examined. Among pharmacologic interventions available for long-term treatment of bipolar disorder, there is a strong clinical trend away from monotherapy and toward combination therapy. Lithium, lamotrigine, olanzapine, and aripiprazole have all shown substantial improvements in relapse rates compared with placebo. Although some of these medications show superior results compared with the others in preventing the recurrence of either depressive or manic episodes, only anecdotal evidence exists regarding their effect on cognition. Combination therapy with antipsychotics or antidepressants has also been shown to produce better syndromal outcomes in people with bipolar disorder, but inadequate evidence is available on cognitive outcomes. Substantial information is needed regarding the prevalence and causes of cognitive dysfunction in bipolar disorder, the effects of existing treatments on cognition, and long-term treatments to improve cognition and functioning.

  4. Rapid, simple, and cost-effective treatments to achieve long-term hydrophilic PDMS surfaces

    NASA Astrophysics Data System (ADS)

    Hemmilä, Samu; Cauich-Rodríguez, Juan V.; Kreutzer, Joose; Kallio, Pasi

    2012-10-01

    This paper describes rapid, simple, and cost-effective treatments for producing biocompatible and long-term hydrophilic polydimethylsiloxane (PDMS) surfaces identified in an experimental study investigating 39 treatments in all. The wetting of the surfaces was monitored during six months. Changes in surface morphology and chemical composition were also analyzed. Some of the treatments are presented here for the first time, while for earlier presented treatments the selection of investigated parameters was wider and the observation period for the surface wetting longer. The PDMS surfaces were modified by surface activation, physisorption, and synthesis of both “grafting to” and “grafting from” polymer brushes. In surface activation, the PDMS sample was exposed to oxygen plasma, with several combinations of exposure time and RF power. In the physisorption and synthesis of polymer brushes, three commercially available and biocompatible chemicals were used: 2-hydroxyethyl methacrylate (HEMA), polyethylene glycol (PEG), and polyvinylpyrrolidone (PVP). Thirty-three of the 39 treatments rendered the PDMS hydrophilic, and in 12 cases the hydrophilicity lasted at least six months. Seven of these long-term hydrophilic coatings supported a contact angle of 30° or less. Three of the long-lasting hydrophilic coatings required only minutes to prepare.

  5. Case report: long-term survival of an infant syndromic patient affected by atypical teratoid-rhabdoid tumor

    PubMed Central

    2013-01-01

    Background Atypical teratoid rhabdoid tumor (ATRT) patients display a dismal median overall survival of less than 1 year. A consistent fraction of cases carries de-novo SMARCB1/INI1 constitutional mutations in the setting of the “rhabdoid tumor predisposition syndrome” and the outcome is worst in infant syndromic ATRT patients. Case presentation We here describe a patient affected by mosaic Klinefelter syndrome and by rhabdoid tumor predisposition syndrome caused by constitutional SMARCB1/INI1 heterozygous mutation c.118C>T (Arg40X). Patient’s ATRT primary tumor occurred at 2 years of age concurrent with metastatic lesions. The patient was rendered without evidence of disease by combined surgery, high-dose poli-chemotherapy and craniospinal irradiation, followed by autologous hematopoietic stem cell transplantation. At the onset of a spinal lesion 5.5 years later, both tumors were pathologically and molecularly evaluated at the national central pathology review board and defined as ATRT in a syndromic patient, with strong evidence of a clonal origin of the two lesions. The patient was then treated according to SIOP guidelines and is now alive without evidence of disease 24 months after the detection of metastatic disease and 90 months after the original diagnosis. Conclusion The report underscores the current utility of multiple comprehensive approaches for the correct diagnosis and clinical management of patients affected by rare and atypical brain neoplasms. Successful local control of disease and achievement of long-term survival is possible in ATRT patients even in the setting of rhabdoid tumor predisposition syndrome, infant age at diagnosis and metastatic spread of disease, thus justifying the efforts for the management of this severe condition. PMID:23510391

  6. Reduced Long-Term Relative Survival in Females and Younger Adults Undergoing Cardiac Surgery: A Prospective Cohort Study

    PubMed Central

    Enger, Tone Bull; Pleym, Hilde; Stenseth, Roar; Greiff, Guri; Wahba, Alexander; Videm, Vibeke

    2016-01-01

    Objectives To assess long-term survival and mortality in adult cardiac surgery patients. Methods 8,564 consecutive patients undergoing cardiac surgery in Trondheim, Norway from 2000 until censoring 31.12.2014 were prospectively followed. Observed long-term mortality following surgery was compared to the expected mortality in the Norwegian population, matched on gender, age and calendar year. This enabled assessment of relative survival (observed/expected survival rates) and relative mortality (observed/expected deaths). Long-term mortality was compared across gender, age and surgical procedure. Predictors of reduced survival were assessed with multivariate analyses of observed and relative mortality. Results During follow-up (median 6.4 years), 2,044 patients (23.9%) died. The observed 30-day, 1-, 3- and 5-year mortality rates were 2.2%, 4.4%, 8.2% and 13.8%, respectively, and remained constant throughout the study period. Comparing observed mortality to that expected in a matched sample from the general population, patients undergoing cardiac surgery showed excellent survival throughout the first seven years of follow-up (relative survival ≥ 1). Subsequently, survival decreased, which was more pronounced in females and patients undergoing other procedures than isolated coronary artery bypass grafting (CABG). Relative mortality was higher in younger age groups, females and patients undergoing aortic valve replacement (AVR). The female survival advantage in the general population was obliterated (relative mortality ratio (RMR) 1.35 (1.19–1.54), p<0.001). Increasing observed long-term mortality seen with ageing was due to population risk, and younger age was independently associated with increased relative mortality (RMR per 5 years 0.81 (0.79–0.84), p<0.001)). Conclusions Cardiac surgery patients showed comparable survival to that expected in the general Norwegian population, underlining the benefits of cardiac surgery in appropriately selected patients. The

  7. mTOR Inhibition and Alloantigen-Specific Regulatory T Cells Synergize to Promote Long-Term Graft Survival in Immunocompetent Recipients1

    PubMed Central

    Raimondi, Giorgio; Sumpter, Tina L.; Matta, Benjamin M.; Pillai, Mahesh; Corbitt, Natasha; Vodovotz, Yoram; Wang, Zhiliang; Thomson, Angus W.

    2010-01-01

    Minimization of immunosuppression and donor-specific tolerance to MHC-mismatched organ grafts are important clinical goals. The therapeutic potential of regulatory T cells (Treg) has been demonstrated, but conditions for optimizing their in vivo function post-transplant in nonlymphocyte-depleted hosts remain undefined. Herein, we address mechanisms through which inhibition of the mammalian target of rapamycin (Rapa) (mTOR) synergizes with alloAg-specific Treg (AAsTreg), to permit long-term, donor-specific heart graft survival in immunocompetent hosts. Crucially, immature allogeneic dendritic cells (DC) allowed AAsTreg selection in vitro, with minimal expansion of unwanted (TH17) cells. The rendered Treg potently inhibited T cell proliferation in an Ag-specific manner. However, these AAsTreg remained unable to control T cells stimulated by allogeneic mature DC, – a phenomenon dependent on the release of pro-inflammatory cytokines. In vivo, Rapa administration reduced danger-associated IL-6 production, T cell proliferation and graft infiltration. Based on these observation, AAsTreg were administered post-transplant (d7) in combination with a short course of Rapa and rendered >80% long-term (>150 d) graft survival, a result superior to that achieved with polyclonal Treg. Moreover, graft protection was alloAg-specific. Significantly, long-term graft survival was associated with alloreactive T cell anergy. These findings delineate combination of transient mTOR inhibition with appropriate AAsTreg selection as an effective approach to promote long-term organ graft survival. PMID:20007530

  8. Repair or Replacement for Isolated Tricuspid Valve Pathology? Insights from a Surgical Analysis on Long-Term Survival

    PubMed Central

    Farag, Mina; Arif, Rawa; Sabashnikov, Anton; Zeriouh, Mohamed; Popov, Aron-Frederik; Ruhparwar, Arjang; Schmack, Bastian; Dohmen, Pascal M.; Szabó, Gábor; Karck, Matthias; Weymann, Alexander

    2017-01-01

    Background Long-term follow-up data concerning isolated tricuspid valve pathology after replacement or reconstruction is limited. Current American Heart Association guidelines equally recommend repair and replacement when surgical intervention is indicated. Our aim was to investigate and compare operative mortality and long-term survival in patients undergoing isolated tricuspid valve repair surgery versus replacement. Material/Methods Between 1995 and 2011, 109 consecutive patients underwent surgical correction of tricuspid valve pathology at our institution for varying structural pathologies. A total of 41 (37.6%) patients underwent tricuspid annuloplasty/repair (TAP) with or without ring implantation, while 68 (62.3%) patients received tricuspid valve replacement (TVR) of whom 36 (53%) were mechanical and 32 (47%) were biological prostheses. Results Early survival at 30 days after surgery was 97.6% in the TAP group and 91.1% in the TVR group. After 6 months, 89.1% in the TAP group and 87.8% in the TVR group were alive. In terms of long-term survival, there was no further mortality observed after one year post surgery in both groups (Log Rank p=0.919, Breslow p=0.834, Tarone-Ware p=0.880) in the Kaplan-Meier Survival analysis. The 1-, 5-, and 8-year survival rates were 85.8% for TAP and 87.8% for TVR group. Conclusions Surgical repair of the tricuspid valve does not show survival benefit when compared to replacement. Hence valve replacement should be considered generously in patients with reasonable suspicion that regurgitation after repair will reoccur. PMID:28236633

  9. Outcomes and long-term survival of coronary artery surgery: The controversial role of opium as risk marker

    PubMed Central

    Najafi, Mahdi; Jahangiry, Leila; Mortazavi, Seyedeh Hamideh; Jalali, Arash; Karimi, Abbasali; Bozorgi, Ali

    2016-01-01

    AIM To study survival in isolated coronary artery bypass graft (CABG) patients and to evaluate the impact of preoperative chronic opium consumption on long-term outcome. METHODS Cohort of 566 isolated CABG patients as Tehran Heart Center cardiac output measurement was conducted. Daily evaluation until discharge as well as 4- and 12-mo and 6.5-year follow-up information for survival status were fulfilled for all patients. Long-term 6.5-year overall and opium-stratified survival, adjusted survival curves based on opium consumption as well as possible predictors of all-cause mortality using multiple cox regression were determined by statistical analysis. RESULTS Six point five-year overall survival was 91.8%; 86.6% in opium consumers and 92.7% in non-opium consumers (P = 0.035). Patients with positive history of opium consumption significantly tended to have lower ejection fraction (EF), higher creatinine level and higher prevalence of myocardial infarction. Multiple predictors of all-cause mortality included age, body mass index, EF, diabetes mellitus and cerebrovascular accident. The hazard ratio (HR) of 2.09 for the risk of mortality in opium addicted patients with a borderline P value (P = 0.052) was calculated in this model. Further adjustment with stratification based on smoking and opium addiction reduced the HR to 1.20 (P = 0.355). CONCLUSION Simultaneous impact of smoking as a confounding variable in most of the patients prevents from definitive judgment on the role of opium as an independent contributing factor in worse long-term survival of CABG patients in addition to advanced age, low EF, diabetes mellitus and cerebrovascular accident. Meanwhile, our findings do not confirm any cardio protective role for opium to improve outcome in coronary patients with the history of smoking. Further studies are needed to clarify pure effect of opium and warrant the aforementioned findings. PMID:27957254

  10. Long-term management strategies to achieve optimal function in patients with bipolar disorder.

    PubMed

    Keck, Paul E

    2006-12-01

    Predictors of poor functional outcome in patients with bipolar disorder include psychiatric and medical comorbidity, interepisode subsyndromal symptoms, psychosis during manic or mixed episode, and low premorbid functioning. Cognitive dysfunction may also contribute to functional impairment. Psychosocial intervention has shown success in improving syndromal outcomes for people with bipolar disorder. Lithium, lamotrigine, olanzapine, and aripiprazole have all shown substantial improvements in relapse rates compared with placebo. Combination therapy with antipsychotics and antidepressants has also been shown to produce improvement in symptoms in people with bipolar disorder. However, limited evidence is available for the effects of these treatments on cognitive outcomes. This review discusses treatment strategies for the long-term management of bipolar disorder and functional outcome measures associated with these treatments.

  11. Cell contact as an independent factor modulating cardiac myocyte hypertrophy and survival in long-term primary culture

    NASA Technical Reports Server (NTRS)

    Clark, W. A.; Decker, M. L.; Behnke-Barclay, M.; Janes, D. M.; Decker, R. S.

    1998-01-01

    Cardiac myocytes maintained in cell culture develop hypertrophy both in response to mechanical loading as well as to receptor-mediated signaling mechanisms. However, it has been shown that the hypertrophic response to these stimuli may be modulated through effects of intercellular contact achieved by maintaining cells at different plating densities. In this study, we show that the myocyte plating density affects not only the hypertrophic response and features of the differentiated phenotype of isolated adult myocytes, but also plays a significant role influencing myocyte survival in vitro. The native rod-shaped phenotype of freshly isolated adult myocytes persists in an environment which minimizes myocyte attachment and spreading on the substratum. However, these conditions are not optimal for long-term maintenance of cultured adult cardiac myocytes. Conditions which promote myocyte attachment and spreading on the substratum, on the other hand, also promote the re-establishment of new intercellular contacts between myocytes. These contacts appear to play a significant role in the development of spontaneous activity, which enhances the redevelopment of highly differentiated contractile, junctional, and sarcoplasmic reticulum structures in the cultured adult cardiomyocyte. Although it has previously been shown that adult cardiac myocytes are typically quiescent in culture, the addition of beta-adrenergic agonists stimulates beating and myocyte hypertrophy, and thereby serves to increase the level of intercellular contact as well. However, in densely-plated cultures with intrinsically high levels of intercellular contact, spontaneous contractile activity develops without the addition of beta-adrenergic agonists. In this study, we compare the function, morphology, and natural history of adult feline cardiomyocytes which have been maintained in cultures with different levels of intercellular contact, with and without the addition of beta-adrenergic agonists

  12. "The end of good luck''--long-term survival without anticoagulation: a case report and review of the literature.

    PubMed

    Gul, Enes E; Altunbas, Gokhan; Kayrak, Mehmet; Ozdemir, Kurtulus

    2012-01-01

    Long-term anticoagulation in patients with metallic prosthetic valve disease is required according to current guidelines. We describe a patient with a functioning mitral mechanical valve without anticoagulation for 27 years. A 46-year-old man admitted to the emergency department with complains of palpitation. The patient had a mitral valve replacement because of severe mitral stenosis. He discontinued warfarin treatment 1 month after surgery because of the unavailability of this drug in Turkey. Transthoracic echocardiography revealed functioning metalic mitral valve with a mean gradient of 9 mm Hg. Fluoroscopy showed normal excursions of the mechanical mitral valve. Transesophageal echocardiography was performed and revealed fresh thrombus formation in the left atrial appendix. Admission international normalized ration (INR) level was 1.79. Due to the higher INR level and long-term survival, genetic analysis of warfarin polymorphism was performed. There was a homozygous mutation in the vitamin K epoxide reductase complex 1 (VKORC1) 1173C>T and 1639G>A genotypes. The possible explanations of long-term survival and baseline higher INR level were linked to the mutation in warfarin metabolism. We also briefly review the literature.

  13. Long-term Survival and Virulence of Mycobacterium leprae in Amoebal Cysts

    PubMed Central

    Wheat, William H.; Casali, Amy L.; Thomas, Vincent; Spencer, John S.; Lahiri, Ramanuj; Williams, Diana L.; McDonnell, Gerald E.; Gonzalez-Juarrero, Mercedes; Brennan, Patrick J.; Jackson, Mary

    2014-01-01

    Leprosy is a curable neglected disease of humans caused by Mycobacterium leprae that affects the skin and peripheral nerves and manifests clinically in various forms ranging from self-resolving, tuberculoid leprosy to lepromatous leprosy having significant pathology with ensuing disfiguration disability and social stigma. Despite the global success of multi-drug therapy (MDT), incidences of clinical leprosy have been observed in individuals with no apparent exposure to other cases, suggestive of possible non-human sources of the bacteria. In this study we show that common free-living amoebae (FLA) can phagocytose M. leprae, and allow the bacillus to remain viable for up to 8 months within amoebic cysts. Viable bacilli were extracted from separate encysted cocultures comprising three common Acanthamoeba spp.: A. lenticulata, A. castellanii, and A. polyphaga and two strains of Hartmannella vermiformis. Trophozoites of these common FLA take up M. leprae by phagocytosis. M. leprae from infected trophozoites induced to encyst for long-term storage of the bacilli emerged viable by assessment of membrane integrity. The majority (80%) of mice that were injected with bacilli extracted from 35 day cocultures of encysted/excysted A. castellanii and A. polyphaga showed lesion development that was similar to mice challenged with fresh M. leprae from passage mice albeit at a slower initial rate. Mice challenged with coculture-extracted bacilli showed evidence of acid-fast bacteria and positive PCR signal for M. leprae. These data support the conclusion that M. leprae can remain viable long-term in environmentally ubiquitous FLA and retain virulence as assessed in the nu/nu mouse model. Additionally, this work supports the idea that M. leprae might be sustained in the environment between hosts in FLA and such residence in FLA may provide a macrophage-like niche contributing to the higher-than-expected rate of leprosy transmission despite a significant decrease in human reservoirs

  14. Long-term survival and virulence of Mycobacterium leprae in amoebal cysts.

    PubMed

    Wheat, William H; Casali, Amy L; Thomas, Vincent; Spencer, John S; Lahiri, Ramanuj; Williams, Diana L; McDonnell, Gerald E; Gonzalez-Juarrero, Mercedes; Brennan, Patrick J; Jackson, Mary

    2014-12-01

    Leprosy is a curable neglected disease of humans caused by Mycobacterium leprae that affects the skin and peripheral nerves and manifests clinically in various forms ranging from self-resolving, tuberculoid leprosy to lepromatous leprosy having significant pathology with ensuing disfiguration disability and social stigma. Despite the global success of multi-drug therapy (MDT), incidences of clinical leprosy have been observed in individuals with no apparent exposure to other cases, suggestive of possible non-human sources of the bacteria. In this study we show that common free-living amoebae (FLA) can phagocytose M. leprae, and allow the bacillus to remain viable for up to 8 months within amoebic cysts. Viable bacilli were extracted from separate encysted cocultures comprising three common Acanthamoeba spp.: A. lenticulata, A. castellanii, and A. polyphaga and two strains of Hartmannella vermiformis. Trophozoites of these common FLA take up M. leprae by phagocytosis. M. leprae from infected trophozoites induced to encyst for long-term storage of the bacilli emerged viable by assessment of membrane integrity. The majority (80%) of mice that were injected with bacilli extracted from 35 day cocultures of encysted/excysted A. castellanii and A. polyphaga showed lesion development that was similar to mice challenged with fresh M. leprae from passage mice albeit at a slower initial rate. Mice challenged with coculture-extracted bacilli showed evidence of acid-fast bacteria and positive PCR signal for M. leprae. These data support the conclusion that M. leprae can remain viable long-term in environmentally ubiquitous FLA and retain virulence as assessed in the nu/nu mouse model. Additionally, this work supports the idea that M. leprae might be sustained in the environment between hosts in FLA and such residence in FLA may provide a macrophage-like niche contributing to the higher-than-expected rate of leprosy transmission despite a significant decrease in human reservoirs

  15. The long-term survival of Escherichia coli in river water.

    PubMed

    Flint, K P

    1987-09-01

    Escherichia coli introduced into autoclaved filtered river water survived for up to 260 d at temperatures from 4 degrees to 25 degrees C with no loss of viability. Survival times were less in water which was only filtered through either a Whatman filter paper or a 0.45 micron Millipore filter or in untreated water, suggesting that competition with the natural microbial flora of the water was the primary factor in the disappearance of the introduced bacteria. Survival was also dependent upon temperature with survival at 4 degrees C greater than 15 degrees C greater than 25 degrees C greater than 37 degrees C for any water sample. Direct counts showed that bacterial cells did not disappear as the viable count decreased. The possession of the antibiotic resistance plasmids, R1drd-19 or R144-3, did not enhance survival nor cause a faster rate of decay, indicating that the metabolic burden imposed by a plasmid was not a factor in survival under starvation conditions. There was no evidence of transfer of either plasmid at 15 degrees C or of loss of plasmid function during starvation.

  16. Long-Term Follow Up of CSRP: Understanding Students' Academic Achievement Post-Treatment

    ERIC Educational Resources Information Center

    Lennon, Jaclyn M.; Li-Grining, Christine; Raver, C. Cybele; Pess, Rachel A.

    2011-01-01

    In this poster presentation, the authors examine the impact of Chicago School Readiness Project (CSRP) on students' academic achievement in elementary school. First, they provide upper- and lower-bound estimates of the impact of CSRP on students' academic achievement, taking into account their subsequent nonrandom selection into higher versus…

  17. Culture Volume and Vessel Affect Long-Term Survival, Mutation Frequency, and Oxidative Stress of Escherichia coli

    PubMed Central

    Kram, Karin E.

    2014-01-01

    Bacteria such as Escherichia coli are frequently studied during exponential- and stationary-phase growth. However, many strains can survive in long-term stationary phase (LTSP), without the addition of nutrients, from days to several years. During LTSP, cells experience a variety of stressors, including reactive oxidative species, nutrient depletion, and metabolic toxin buildup, that lead to physiological responses and changes in genetic stability. In this study, we monitored survival during LTSP, as well as reporters of genetic and physiological change, to determine how the physical environment affects E. coli during long-term batch culture. We demonstrate differences in yield during LTSP in cells incubated in LB medium in test tubes versus Erlenmeyer flasks, as well as growth in different volumes of medium. We determined that these differences are only partially due to differences in oxygen levels by incubating the cells in different volumes of media under anaerobic conditions. Since we hypothesized that differences in long-term survival are the result of changes in physiological outputs during the late log and early stationary phases, we monitored alkalization, mutation frequency, oxidative stress response, and glycation. Although initial cell yields are essentially equivalent under each condition tested, physiological responses vary greatly in response to culture environment. Incubation in lower-volume cultures leads to higher oxyR expression but lower mutation frequency and glycation levels, whereas incubation in high-volume cultures has the opposite effect. We show here that even under commonly used experimental conditions that are frequently treated as equivalent, the stresses experienced by cells can differ greatly, suggesting that culture vessel and incubation conditions should be carefully considered in the planning or analysis of experiments. PMID:24375138

  18. Long-term survival in elderly patients with a do-not-intubate order treated with noninvasive mechanical ventilation

    PubMed Central

    Scarpazza, Paolo; Incorvaia, Cristoforo; Amboni, Paolo; di Franco, Giuseppe; Raschi, Stefania; Usai, Pierfranco; Bernareggi, Monica; Bonacina, Cristiano; Melacini, Chiara; Cattaneo, Roberta; Bencini, Serena; Pravettoni, Chiara; Riario-Sforza, Gian Galeazzo; Passalacqua, Gianni; Casali, Walter

    2011-01-01

    Background: Noninvasive mechanical ventilation (NIMV) is an effective tool in treating patients with acute respiratory failure (ARF), since it reduces both the need for endotracheal intubation and the mortality in comparison with nonventilated patients. A particular issue is represented by the outcome of NIMV in patients referred to the emergency department for ARF and with a do-not-intubate (DNI) status because of advanced age or excessively critical conditions. This study evaluated long-term survival in a group of elderly patients with acute hypercapnic ARF who had a DNI order and who were successfully treated by NIMV. Methods: The population consisted of 54 patients with a favorable outcome after NIMV for ARF. They were followed up for 3 years by regular control visits, with at least one visit every 4 months, or as needed according to the patient’s condition. Of these, 31 continued NIMV at home and 23 were on long-term oxygen therapy (LTOT) alone. Results: A total of 16 of the 52 patients had not survived at the 1-year follow-up, and another eight patients died during the 3-year observation, with an overall mortality rate of 30.8% after 1 year and 46.2% after 3 years. Comparing patients who continued NIMV at home with those who were on LTOT alone, 9 of the 29 patients on home NIMV died (6 after 1 year and 3 after 3 years) and 15 of the 23 patients on LTOT alone died (10 after 1 year and 5 after 3 years). Conclusion: These results show that elderly patients with ARF successfully treated by NIMV following a DNI order have a satisfactory long-term survival. PMID:21814461

  19. Sporulation and Germination patterns - hedging a bet on long term microbial survivability in dry soil

    NASA Astrophysics Data System (ADS)

    Claes, N.; Or, D.

    2012-04-01

    Soil hosts unparalleled diversity of microbial life that is constantly challenged by the vagaries of fluctuating ambient conditions. Desiccation stresses play a key role not only by directly affecting individual bacterial cells, but also by shaping diffusion pathways and cell dispersion. The gradual thinning and fragmentation of the aqueous environment during drying have led to different survival mechanisms including dormancy and sporulation, resulting in a highly resistive state capable of surviving extreme and prolonged environmental stresses until conditions improve in the future. Our aim is to investigate how temporal changes in hydration status shape microbial communities over time, based on simple survival strategy rules for each individual bacterium. The two survival strategies considered are dormancy and sporulation. Dormancy is the state in which bacterial cells significantly reduce their metabolism with minor morphological adaptations. The required energy and time for attaining this state are low relative to sporulation costs. Sporulation involves several morphological and biochemical changes that result in a resistive capsule that endures extreme stresses over long periods of time. The working hypothesis is that different micro-ecological conditions and community compositions would result from temporal patterns and magnitude of desiccation stresses. An Individual Based Model (IBM) considering habitats on rough soil surfaces and local effects of micro-hydrological conditions on dispersion and nutrient diffusion would enable systematic study of emerging communities over extended periods. Different population compositions are expected to emerge based on low and high frequency, duration and amplitudes of wetting-drying cycles reflecting relative success or failure of survival strategy.

  20. Sarcopenia is an Independent Predictor of Severe Postoperative Complications and Long-Term Survival After Radical Gastrectomy for Gastric Cancer

    PubMed Central

    Zhuang, Cheng-Le; Huang, Dong-Dong; Pang, Wen-Yang; Zhou, Chong-Jun; Wang, Su-Lin; Lou, Neng; Ma, Liang-Liang; Yu, Zhen; Shen, Xian

    2016-01-01

    Abstract Currently, the association between sarcopenia and long-term prognosis after gastric cancer surgery has not been investigated. Moreover, the association between sarcopenia and postoperative complications remains controversial. This large-scale retrospective study aims to ascertain the prevalence of sarcopenia and assess its impact on postoperative complications and long-term survival in patients undergoing radical gastrectomy for gastric cancer. From December 2008 to April 2013, the clinical data of all patients who underwent elective radical gastrectomy for gastric cancer were collected prospectively. Only patients with available preoperative abdominal CT scan within 30 days of surgery were considered for analysis. Skeletal muscle mass was determined by abdominal (computed tomography) CT scan, and sarcopenia was diagnosed by the cut-off values obtained by means of optimum stratification. Univariate and multivariate analyses evaluating risk factors of postoperative complications and long-term survival were performed. A total of 937 patients were included in this study, and 389 (41.5%) patients were sarcopenic based on the diagnostic cut-off values (34.9 cm2/m2 for women and 40.8 cm2/m2 for men). Sarcopenia was an independent risk factor for severe postoperative complications (OR = 3.010, P < 0.001), but not for total complications. However, sarcopenia did not show significant association with operative mortality. Moreover, sarcopenia was an independent predictor for poorer overall survival (HR = 1.653, P < 0.001) and disease-free survival (HR = 1.620, P < 0.001). Under the adjusted tumor-node-metastasis (TNM) stage, sarcopenia remained an independent risk factor for overall survival and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I. Sarcopenia is an independent predictive factor of severe postoperative complications after radical gastrectomy for gastric cancer. Moreover

  1. Induction chemoradiation therapy prior to esophagectomy is associated with superior long-term survival for esophageal cancer.

    PubMed

    Speicher, P J; Wang, X; Englum, B R; Ganapathi, A M; Yerokun, B; Hartwig, M G; D'Amico, T A; Berry, M F

    2015-01-01

    The purpose of this study was to examine the role of induction chemoradiation in the treatment of potentially resectable locally advanced (T2-3N0 and T1-3N+) esophageal cancer utilizing a large national database. The National Cancer Data Base (NCDB) was queried for all patients undergoing esophagectomy for clinical T2-3N0 and T1-3N+ esophageal cancer of the mid- or lower esophagus. Patients were stratified by the use of induction chemoradiation therapy versus surgery-first. Trends were assessed with the Cochran-Armitage test. Predictors of receiving induction therapy were evaluated with multivariable logistic regression. A propensity-matched analysis was conducted to compare outcomes between groups, and the Kaplan-Meier method was used to estimate long-term survival. Within the NCDB, 7921 patients were identified, of which 6103 (77.0%) were treated with chemoradiation prior to esophagectomy, while the remaining 1818 (23.0%) were managed with surgery-first. Use of induction therapy increased over time, with an absolute increase of 11.8% from 2003-2011 (P < 0.001). As revealed by the propensity model, induction therapy was associated with higher rates of negative margins and shorter hospital length of stay, but no differences in unplanned readmission and 30-day mortality rates. In unadjusted survival analysis, induction therapy was associated with better long-term survival compared to a strategy of surgery-first, with 5-year survival rates of 37.2% versus 28.6%, P < 0.001. Following propensity score matching analysis, the use of induction therapy maintained a significant survival advantage over surgery-first (5-year survival: 37.9% vs. 28.7%, P < 0.001). Treatment with induction chemoradiation therapy prior to surgical resection is associated with significant improvement in long-term survival, even after adjusting for confounders with a propensity model. Induction therapy should be considered in all medically appropriate patients with resectable cT2-3N0 and cT1-3N

  2. High rates of long-term survival of deep-sea infauna in the laboratory

    NASA Astrophysics Data System (ADS)

    Weinberg, James R.

    1990-08-01

    Living bivalves ( Nucula, Thyasira), a gastropod ( Frigidoalvania brychia) and a calcareous foraminiferan ( Laticarinina pauperata), from 775 m depth in the northwest Atlantic, were maintained in the laboratory for 772 days to measure their survival. The organisms, <4 mm in size, were maintained at 1 atm and at 5°C in cups containing sediment and seawater. Over the 772 day period, 46% of all bivalves and one of two gastropods survived. Minimum estimates for survival of L. pauperata in six containers ranged from 0 to 67% for a 1-2 year period. This study demonstrates that it is feasible to maintain continental slope infauna in the laboratory for long periods of time. Such organisms could be used in experiments that examine their mobility, responses to different sediments and foods, and sizes and shapes of biogenic structures produced in sediments.

  3. Percutaneous Irreversible Electroporation: Long-term survival analysis of 71 patients with inoperable malignant hepatic tumors

    PubMed Central

    Niessen, C.; Thumann, S.; Beyer, L.; Pregler, B.; Kramer, J.; Lang, S.; Teufel, A.; Jung, E. M.; Stroszczynski, C.; Wiggermann, P.

    2017-01-01

    Aim of this retrospective analysis was to evaluate the survival times after percutaneous irreversible electroporation (IRE) in inoperable liver tumors not amenable to thermal ablation. 71 patients (14 females, 57 males, median age 63.5 ± 10.8 years) with 103 liver tumors were treated in 83 interventions using IRE (NanoKnife® system). The median tumor short-axis diameter was 1.9 cm (minimum 0.4 cm, maximum 4.5 cm). 35 patients had primary liver tumors and 36 patients had liver metastases. The Kaplan-Meier method was employed to calculate the survival rates, and the different groups were compared using multivariate log-rank and Wilcoxon tests. The overall median survival time was 26.3 months; the median survival of patients with primary land secondary liver cancer did not significantly differ (26.8 vs. 19.9 months; p = 0.41). Patients with a tumor diameter >3 cm (p < 0.001) or more than 2 lesions (p < 0.005) died significantly earlier than patients with smaller or fewer tumors. Patients with hepatocellular carcinoma and Child-Pugh class B or C cirrhosis died significantly earlier than patients with Child-Pugh class A (p < 0.05). Patients with very early stage HCC survived significantly longer than patients with early stage HCC with a median survival of 22.3 vs. 13.7 months (p < 0.05). PMID:28266600

  4. Optimization of 15 parameters influencing the long-term survival of bacteria in aquatic systems

    NASA Technical Reports Server (NTRS)

    Obenhuber, D. C.

    1993-01-01

    NASA is presently engaged in the design and development of a water reclamation system for the future space station. A major concern in processing water is the control of microbial contamination. As a means of developing an optimal microbial control strategy, studies were undertaken to determine the type and amount of contamination which could be expected in these systems under a variety of changing environmental conditions. A laboratory-based Taguchi optimization experiment was conducted to determine the ideal settings for 15 parameters which influence the survival of six bacterial species in aquatic systems. The experiment demonstrated that the bacterial survival period could be decreased significantly by optimizing environmental conditions.

  5. Surviving the Holocaust: a meta-analysis of the long-term sequelae of a genocide.

    PubMed

    Barel, Efrat; Van IJzendoorn, Marinus H; Sagi-Schwartz, Abraham; Bakermans-Kranenburg, Marian J

    2010-09-01

    The current set of meta-analyses elucidates the long-term psychiatric, psychosocial, and physical consequences of the Holocaust for survivors. In 71 samples with 12,746 participants Holocaust survivors were compared with their counterparts (with no Holocaust background) on physical health, psychological well-being, posttraumatic stress symptoms, psychopathological symptomatology, cognitive functioning, and stress-related physiology. Holocaust survivors were less well adjusted, as apparent from studies on nonselected samples (trimmed combined effect size d = 0.22, 95% CI [0.13, 0.31], N = 9,803) and from studies on selected samples (d = 0.45, 95% CI [0.32, 0.59], N = 2,943). In particular, they showed substantially more posttraumatic stress symptoms (nonselect studies: d = 0.72, 95% CI [0.46, 0.98], N = 1,763). They did not lag, however, much behind their comparisons in several other domains of functioning (i.e., physical health, stress-related physical measures, and cognitive functioning) and showed remarkable resilience. The coexistence of stress-related symptoms and good adaptation in some other areas of functioning may be explained by the unique characteristics of the symptoms of Holocaust survivors, who combine resilience with the use of defensive mechanisms. In most domains of functioning no differences were found between Israeli samples and samples from other countries. The exception was psychological well-being: For this domain it was found that living in Israel rather than elsewhere can serve as a protective factor. A biopsychological stress-diathesis model is used to interpret the findings, and future directions for research and social policy are discussed.

  6. Survival Outcomes and Predictive Factors for Female Urethral Cancer: Long-term Experience with Korean Patients.

    PubMed

    Kang, Minyong; Jeong, Chang Wook; Kwak, Cheol; Kim, Hyeon Hoe; Ku, Ja Hyeon

    2015-08-01

    The aim of this study was to evaluate female urethral cancer (UCa) patients treated and followed-up during a time period spanning more than 20 yr at single institution in Korea. We reviewed medical records of 21 consecutive patients diagnosed with female UCa at our institution between 1991 and 2012. After exclusion of two patients due to undefined histology, we examined clinicopathological variables, as well as survival outcomes of 19 patients with female UCa. A Cox proportional hazards ratio model was used to identify significant predictors of prognosis according to variables. The median age at diagnosis was 59 yr, and the median follow-up duration was 87.0 months. The most common initial symptoms were voiding symptoms and blood spotting. The median tumor size was 3.4 cm, and 55% of patients had lesions involving the entire urethra. The most common histologic type was adenocarcinoma, and the second most common type was urothelial carcinoma. Fourteen patients underwent surgery, and 7 of these patients received adjuvant radiation or systemic chemotherapy. Eleven patients experienced tumor recurrence after primary therapy. Patients with high stage disease, advanced T stage (≥T3), and positive lymph nodes had worse survival outcomes compared to their counterparts. Particularly, lymph node positivity and advanced T stage were significant predictive factors for all survival outcomes. Tumor location was the only significant predictor for recurrence-free survival. Although our study included a small number of patients, it conveys valuable information about this rare female urologic malignancy in a Korean population.

  7. Studies on the mechanism of long term survival of Taenia taeniaeformis in rats.

    PubMed

    Kwa, B H; Liew, F Y

    1978-03-01

    An attempt was made to determine if blocking antibody is involved in protecting cysticerci of Taenia taeniaeformis against a host immune response. Immunoflourescence microscopy confirmed that host antibody is presnet on the parasite surface within the capsule. To test if the larvae can still survive after such a coat of blocking antibody is removed, the larvae were trysinised and then implanted into recipients. The results indicate that blocking antibody could be involved in the survival of 1 year old established larvae. Untrypsinised larvae were normal 14 days after implantation into control or immunised rats. Trypsinised larvae implanted in control rats were alive but showed on intense cell adherence on their surface. On the other hand, trypsinised larvae implanted into immunised rats were dead and completely encapsulated. However, experiments with 1 month old larvae were inconclusive.

  8. From Exit to Entry: Long-term Survival and Transmission of Salmonella

    PubMed Central

    Waldner, Landon L.; MacKenzie, Keith D.; Köster,, Wolfgang; White, Aaron P.

    2012-01-01

    Salmonella spp. are a leading cause of human infectious disease worldwide and pose a serious health concern. While we have an improving understanding of pathogenesis and the host-pathogen interactions underlying the infection process, comparatively little is known about the survival of pathogenic Salmonella outside their hosts. This review focuses on three areas: (1) in vitro evidence that Salmonella spp. can survive for long periods of time under harsh conditions; (2) observations and conclusions about Salmonella persistence obtained from human outbreaks; and (3) new information revealed by genomic- and population-based studies of Salmonella and related enteric pathogens. We highlight the mechanisms of Salmonella persistence and transmission as an essential part of their lifecycle and a prerequisite for their evolutionary success as human pathogens. PMID:25436767

  9. Long-term survival after intraluminal brachytherapy for inoperable hilar cholangiocarcinoma: A case report

    PubMed Central

    Chan, Siu-Yin; Poon, Ronnie T.; Ng, Kelvin K.; Liu, Chi-Leung; Chan, Raymond T.; Fan, Sheung-Tat

    2005-01-01

    Surgical resection with a tumor-free margin is the only curative treatment for hilar cholangiocarcinoma (Klatskin tumor). However, over half of the patients present late with unresectable tumors. Radiotherapy using external beam irradiation or intraluminal brachytherapy (ILBT) has been used to treat unresectable hilar cholangiocarcinoma with satisfactory outcome. We reported a patient with unresectable hilar cholangiocarcinoma surviving more than 6 years after combined external beam irradiation and ILBT. PMID:15918211

  10. Long-term survival of an AIDS patient with a tuberculous cerebral abscess.

    PubMed Central

    Gettler, J. F.; Garner, B. F.

    1996-01-01

    Unlike other forms of tuberculosis, tuberculous cerebral abscess is a rare complication of human immunodeficiency virus (HIV) infection and usually presents at a late stage of the disease. This article describes a case of tuberculous cerebral abscess in an HIV-infected patient that was effectively treated with surgery and chemotherapy. The patient has survived more than 5 1/2 years since being diagnosed and remains in good health. PMID:8855653

  11. Long-term survival of an AIDS patient with a tuberculous cerebral abscess.

    PubMed

    Gettler, J F; Garner, B F

    1996-09-01

    Unlike other forms of tuberculosis, tuberculous cerebral abscess is a rare complication of human immunodeficiency virus (HIV) infection and usually presents at a late stage of the disease. This article describes a case of tuberculous cerebral abscess in an HIV-infected patient that was effectively treated with surgery and chemotherapy. The patient has survived more than 5 1/2 years since being diagnosed and remains in good health.

  12. Long-term survival and prognosis associated with conversion surgery in patients with metastatic gastric cancer

    PubMed Central

    Einama, Takahiro; Abe, Hironori; Shichi, Shunsuke; Matsui, Hiroki; Kanazawa, Ryo; Shibuya, Kazuaki; Suzuki, Takashi; Matsuzawa, Fumihiko; Hashimoto, Taku; Kohei, Nakachi; Homma, Shigenori; Kawamura, Hideki; Taketomi, Akinobu

    2017-01-01

    In gastric cancer, primary systemic chemotherapy is the standard approach for the management of patients with initially unresectable metastasis, and it occasionally leads to a reduction in the size of the lesion, which facilitates surgical resection. The aim of this study was to examine the prognosis of patients who were able to undergo complete resection following chemotherapy. A total of 10 patients who underwent radical surgery for stage IV primary gastric cancer after chemotherapy between 2009 and 2015 at the Department of Surgery of Hokkaido Social Work Association Obihiro Hospital (Obihiro, Japan) were retrospectively investigated. Three regimens were used (S-1, n=1; S-1 + cisplatin, n=8; and S-1 + docetaxel, n=1). The mean time from chemotherapy to surgery was 210 days. One total gastrectomy + splenectomy + colectomy, one total gastrectomy + splenectomy, four total gastrectomies and three distal gastrectomies were performed. There were two cases of pancreatic fistula formation postoperatively. All the patients survived for >1 year. Of the 10 patients, 5 survived without recurrence. The median survival time was 871.1 days after diagnosis. Therefore, curative resection after chemotherapy is associated with a better prognosis in stage IV gastric cancer patients.

  13. Long-term survival and integration of transplanted engineered nervous tissue constructs promotes peripheral nerve regeneration.

    PubMed

    Huang, Jason H; Cullen, D Kacy; Browne, Kevin D; Groff, Robert; Zhang, Jun; Pfister, Bryan J; Zager, Eric L; Smith, Douglas H

    2009-07-01

    Although peripheral nerve injury is a common consequence of trauma or surgery, there are insufficient means for repair. In particular, there is a critical need for improved methods to facilitate regeneration of axons across major nerve lesions. Here, we engineered transplantable living nervous tissue constructs to provide a labeled pathway to guide host axonal regeneration. These constructs consisted of stretch-grown, longitudinally aligned living axonal tracts inserted into poly(glycolic acid) tubes. The constructs (allogenic) were transplanted to bridge an excised segment of sciatic nerve in the rat, and histological analyses were performed at 6 and 16 weeks posttransplantation to determine graft survival, integration, and host regeneration. At both time points, the transplanted constructs were found to have maintained their pretransplant geometry, with surviving clusters of graft neuronal somata at the extremities of the constructs spanned by tracts of axons. Throughout the transplanted region, there was an intertwining plexus of host and graft axons, suggesting that the transplanted axons mediated host axonal regeneration across the lesion. By 16 weeks posttransplant, extensive myelination of axons was observed throughout the transplant region. Further, graft neurons had extended axons beyond the margins of the transplanted region, penetrating into the host nerve. Notably, this survival and integration of the allogenic constructs occurred in the absence of immunosuppression therapy. These findings demonstrate the promise of living tissue-engineered axonal constructs to bridge major nerve lesions and promote host regeneration, potentially by providing axon-mediated axonal outgrowth and guidance.

  14. Hodgkin disease (1973-2002): long-term survival and cure fractions.

    PubMed

    Bouliotis, George; Bessell, Eric M

    2015-05-01

    The Nottinghamshire Lymphoma Registry contains the details of all patients diagnosed with lymphoma (since 1 January 1973) within a defined geographical area with a stable population of 1.1 million. The aim of this study was to investigate the relative survival and estimate the cure fraction for patients with Hodgkin disease (HD) using various cure fraction models. Five- and 10-year survival was estimated in comparison to the general population of the same age, gender and year of diagnosis. Relative survival probabilities at 10 years were 52.3% for the 1973-1982 cohort, 67.8% (1983-1992) and 75.7% (1993-2002). The estimated cured fraction (π) was 45%, 65% and 75%, respectively, for the same cohorts. There was very little excess mortality after 4 years from treatment. The prognosis of patients with HD has improved progressively within a defined unselected population over this 30-year period. In the 1993-2002 cohort the prognosis after 4 years of treatment is almost the same as for a normal population.

  15. Predicting long-term growth in students' mathematics achievement: the unique contributions of motivation and cognitive strategies.

    PubMed

    Murayama, Kou; Pekrun, Reinhard; Lichtenfeld, Stephanie; Vom Hofe, Rudolf

    2013-01-01

    This research examined how motivation (perceived control, intrinsic motivation, and extrinsic motivation), cognitive learning strategies (deep and surface strategies), and intelligence jointly predict long-term growth in students' mathematics achievement over 5 years. Using longitudinal data from six annual waves (Grades 5 through 10; Mage  = 11.7 years at baseline; N = 3,530), latent growth curve modeling was employed to analyze growth in achievement. Results showed that the initial level of achievement was strongly related to intelligence, with motivation and cognitive strategies explaining additional variance. In contrast, intelligence had no relation with the growth of achievement over years, whereas motivation and learning strategies were predictors of growth. These findings highlight the importance of motivation and learning strategies in facilitating adolescents' development of mathematical competencies.

  16. Biophysical and biological factors determining the ability to achieve long-term cryobiological preservation

    SciTech Connect

    Mazur, P.

    1997-12-01

    The BESTCapsule will maintain appropriate biological specimens for decades or centuries at cryogenic temperatures in the living state. Maintenance at temperatures below {approximately} {minus}140 C is not a problem. No ordinary chemical reactions in aqueous solutions can occur. The only source of damage will be the slow accumulation of physical damage to DNA from background ionizing radiation. But this source of damage should not become serious in less than a millennium. Rather, the main problem in cryopreservation is to devise procedures for cooling the biological specimens to {minus}196 C and returning them to normal temperatures without inflicting lethal injury. Regardless of the cell type, there are certain encompassing biophysical factors and constraints that determine whether they will survive or die during freezing and thawing. Superimposed on these may be special biological factors that apply to specific cell types. This paper will emphasize the former and give illustrative examples of the latter.

  17. Complete response and long-term survival (>20 years) of a child with tectal glioma: a case report.

    PubMed

    Burzynski, Stanislaw R; Burzynski, Gregory S; Janicki, Tomasz J; Marszalek, Ania

    2015-01-01

    Tectal glioma is a midbrain tumor. The patient generally presents with symptoms related to increased intracranial pressure and requires treatment for hydrocephalus. No effective pharmacological treatments have yet been introduced. This report discusses a case of a 13-year-old male diagnosed with tectal glioma who obtained a complete response and long-term survival after the treatment with antineoplastons (ANP) in phase II trial. Prior treatment consisted of placement of a ventriculoperitoneal shunt. After 6 years of stabilization there had been an increase in tumor size with signs of malignant transformation. The patient received treatment with ANP A10 and AS2-1 infusions for 20 months, obtained a complete response, and was switched to maintenance with ANP capsules. All treatments were discontinued in December 2003. Adverse events according to CTCAE v3.0 included: hypernatremia (two events of grade 3, one event of grade 2, four events of grade 1), one case of fatigue (grade 2), and one allergic reaction (grade 1). Currently, over 20 years from his diagnosis and over 13 years from treatment start he is symptom-free and leads a normal life. This report indicates that it is possible to obtain long-term survival of a child with tectal glioma with currently available investigational treatment.

  18. Long-term survival of a breast cancer patient with extensive liver metastases upon immune and virotherapy: a case report.

    PubMed

    Schirrmacher, Volker; Stücker, Wilfried; Lulei, Maria; Bihari, Akos-Sigmund; Sprenger, Tobias

    2015-01-01

    Liver metastases in breast cancer are associated with a poor prognosis. We report long-term survival of a patient with breast cancer and liver metastases. After operation the patient declined further standard therapy. Instead, she was treated with local hyperthermia, Newcastle disease virus and dendritic cell vaccination at the Immunological and Oncological Center Cologne (IOZK), Germany. A continuous high quality of life was reported and the patient survived more than 66 months after initial diagnosis. No recurrence or further metastases developed under treatment. Following treatment, a long-lasting tumor-reactive memory T-cell responsiveness could be documented. This possibly explains the favorable course of disease. Since this combination of therapies is not restricted to a particular tumor type, further exploration is warranted.

  19. Long-term survival of full trisomy 13 in a 14 year old male: a case report.

    PubMed

    Imataka, G; Hagisawa, S; Nitta, A; Hirabayashi, H; Suzumura, H; Arisaka, O

    2016-03-01

    Long term survival for the cases of trisomy 13 into over a first decade is very rare. We reported here the case of a 14-year-old male karyotype with full type of trisomy 13. In this clinical phenomenon, the case had typical facial, finger and limb anomalies for trisomy 13. Arterial septal defect and patent ductus arteriosus were recognized using ultrasonography after birth. Major cerebral malformation such as holoprosencephaly or cerebellar hypoplasia were also not revealed. After 5 months of his age, artificial ventilation therapy for dyspnea associated with laryngomalacia was required. A tracheotomy was performed at 6 months of his age. After 12 years old, intractable partial epilepsy was recognized. For his partial seizures, a treatment with a combination of two anti-epileptic drugs, valproic acid and levetiracetam, were advised. Now he is alive for 14-years-old and he is the 4th longest surviving patient with full karyotype of trisomy 13.

  20. Implications of subzero metabolic activity on long-term microbial survival in terrestrial and extraterrestrial permafrost.

    PubMed

    Amato, Pierre; Doyle, Shawn M; Battista, John R; Christner, Brent C

    2010-10-01

    The survival of microorganisms over extended time frames in frozen subsurface environments may be limited by chemical (i.e., via hydrolysis and oxidation) and ionizing radiation-induced damage to chromosomal DNA. In an effort to improve estimates for the survival of bacteria in icy terrestrial and extraterrestrial environments, we determined rates of macromolecular synthesis at temperatures down to -15°C in bacteria isolated from Siberian permafrost (Psychrobacter cryohalolentis K5 and P. arcticus 273-4) and the sensitivity of P. cryohalolentis to ionizing radiation. Based on experiments conducted over ≈400 days at -15°C, the rates of protein and DNA synthesis in P. cryohalolentis were <1 to 16 proteins cell(-1) d(-1) and 83 to 150 base pairs (bp) cell(-1) d(-1), respectively; P. arcticus synthesized DNA at rates of 20 to 1625 bp cell(-1) d(-1) at -15°C under the conditions tested. The dose of ionizing radiation at which 37% of the cells survive (D(37)) of frozen suspensions of P. cryohalolentis was 136 Gy, which was ∼2-fold higher (71 Gy) than identical samples exposed as liquid suspensions. Laboratory measurements of [(3)H]thymidine incorporation demonstrate the physiological potential for DNA metabolism at -15°C and suggest a sufficient activity is possible to offset chromosomal damage incurred in near-subsurface terrestrial and martian permafrost. Thus, our data imply that the longevity of microorganisms actively metabolizing within permafrost environments is not constrained by chromosomal DNA damage resulting from ionizing radiation or entropic degradation over geological time.

  1. Long-Term Survival Following Cardiac Arrest Without Implantable Defibrillator Protection in a Hypertrophic Cardiomyopathy Patient

    PubMed Central

    Cetin, Mustafa; Ucar, Ozgul; Canbay, Alper; Cetin, Zehra Guven; Cicekcioglu, Hulya; Diker, Erdem

    2011-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death in young people. Implantable cardioverter defibrillator (ICD) is the optimal therapy in patients with HCM, both for primary or secondary prevention of sudden death. Left ventricular systolic function in HCM is usually normal. However, in few patients, HCM has been reported to progress to a state that is characterized by left ventricular dilation and systolic dysfunction, resembling dilated cardiomyopathy (DCM). Although arrhythmias are common in HCM, advanced or complete atrioventricular block (AV) is very rare. This case report describes a HCM patient who progressed to DCM with advanced AV block and survived 31 years following cardiac arrest without ICD protection.

  2. The Effect of Novel Research Activities on Long-term Survival of Temporarily Captive Steller Sea Lions (Eumetopias jubatus).

    PubMed

    Shuert, Courtney; Horning, Markus; Mellish, Jo-Ann

    2015-01-01

    Two novel research approaches were developed to facilitate controlled access to, and long-term monitoring of, juvenile Steller sea lions for periods longer than typically afforded by traditional fieldwork. The Transient Juvenile Steller sea lion Project at the Alaska SeaLife Center facilitated nutritional, physiological, and behavioral studies on the platform of temporary captivity. Temporarily captive sea lions (TJs, n = 35) were studied, and were intraperitoneally implanted with Life History Transmitters (LHX tags) to determine causes of mortality post-release. Our goal was to evaluate the potential for long-term impacts of temporary captivity and telemetry implants on the survival of study individuals. A simple open-population Cormack-Jolly-Seber mark-recapture model was built in program MARK, incorporating resightings of uniquely branded study individuals gathered by several contributing institutions. A priori models were developed to weigh the evidence of effects of experimental treatment on survival with covariates of sex, age, capture age, cohort, and age class. We compared survival of experimental treatment to a control group of n = 27 free-ranging animals (FRs) that were sampled during capture events and immediately released. Sex has previously been show to differentially affect juvenile survival in Steller sea lions. Therefore, sex was included in all models to account for unbalanced sex ratios within the experimental group. Considerable support was identified for the effects of sex, accounting for over 71% of total weight for all a priori models with delta AICc <5, and over 91% of model weight after removal of pretending variables. Overall, most support was found for the most parsimonious model based on sex and excluding experimental treatment. Models including experimental treatment were not supported after post-hoc considerations of model selection criteria. However, given the limited sample size, alternate models including effects of experimental

  3. The Effect of Novel Research Activities on Long-term Survival of Temporarily Captive Steller Sea Lions (Eumetopias jubatus)

    PubMed Central

    Shuert, Courtney; Horning, Markus; Mellish, Jo-Ann

    2015-01-01

    Two novel research approaches were developed to facilitate controlled access to, and long-term monitoring of, juvenile Steller sea lions for periods longer than typically afforded by traditional fieldwork. The Transient Juvenile Steller sea lion Project at the Alaska SeaLife Center facilitated nutritional, physiological, and behavioral studies on the platform of temporary captivity. Temporarily captive sea lions (TJs, n = 35) were studied, and were intraperitoneally implanted with Life History Transmitters (LHX tags) to determine causes of mortality post-release. Our goal was to evaluate the potential for long-term impacts of temporary captivity and telemetry implants on the survival of study individuals. A simple open-population Cormack-Jolly-Seber mark-recapture model was built in program MARK, incorporating resightings of uniquely branded study individuals gathered by several contributing institutions. A priori models were developed to weigh the evidence of effects of experimental treatment on survival with covariates of sex, age, capture age, cohort, and age class. We compared survival of experimental treatment to a control group of n = 27 free-ranging animals (FRs) that were sampled during capture events and immediately released. Sex has previously been show to differentially affect juvenile survival in Steller sea lions. Therefore, sex was included in all models to account for unbalanced sex ratios within the experimental group. Considerable support was identified for the effects of sex, accounting for over 71% of total weight for all a priori models with delta AICc <5, and over 91% of model weight after removal of pretending variables. Overall, most support was found for the most parsimonious model based on sex and excluding experimental treatment. Models including experimental treatment were not supported after post-hoc considerations of model selection criteria. However, given the limited sample size, alternate models including effects of experimental

  4. Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy

    PubMed Central

    Hazell, Gareth; Shabanpoor, Fazel; Saleh, Amer F.; Bowerman, Melissa; Meijboom, Katharina E.; Zhou, Haiyan; Muntoni, Francesco; Talbot, Kevin; Gait, Michael J.; Wood, Matthew J. A.

    2016-01-01

    The development of antisense oligonucleotide therapy is an important advance in the identification of corrective therapy for neuromuscular diseases, such as spinal muscular atrophy (SMA). Because of difficulties of delivering single-stranded oligonucleotides to the CNS, current approaches have been restricted to using invasive intrathecal single-stranded oligonucleotide delivery. Here, we report an advanced peptide-oligonucleotide, Pip6a-morpholino phosphorodiamidate oligomer (PMO), which demonstrates potent efficacy in both the CNS and peripheral tissues in severe SMA mice following systemic administration. SMA results from reduced levels of the ubiquitously expressed survival motor neuron (SMN) protein because of loss-of-function mutations in the SMN1 gene. Therapeutic splice-switching oligonucleotides (SSOs) modulate exon 7 splicing of the nearly identical SMN2 gene to generate functional SMN protein. Pip6a-PMO yields SMN expression at high efficiency in peripheral and CNS tissues, resulting in profound phenotypic correction at doses an order-of-magnitude lower than required by standard naked SSOs. Survival is dramatically extended from 12 d to a mean of 456 d, with improvement in neuromuscular junction morphology, down-regulation of transcripts related to programmed cell death in the spinal cord, and normalization of circulating insulin-like growth factor 1. The potent systemic efficacy of Pip6a-PMO, targeting both peripheral as well as CNS tissues, demonstrates the high clinical potential of peptide-PMO therapy for SMA. PMID:27621445

  5. Adoptive TIL transfer in the adjuvant setting for melanoma: long-term patient survival.

    PubMed

    Khammari, Amir; Knol, Anne-Chantal; Nguyen, Jean-Michel; Bossard, Céline; Denis, Marc-Guillaume; Pandolfino, Marie-Christine; Quéreux, Gaëlle; Bercegeay, Sylvain; Dréno, Brigitte

    2014-01-01

    Two first analyses of our clinical trial on TIL as adjuvant therapy for melanoma were published in 2002 and 2007. We present here an update of the clinical results after a 17-year median followup. In this trial, disease-free patients were randomly assigned to receive either TIL/IL-2 or IL-2. The relapse-free survival (RFS) was the primary objective. Eighty-eight patients were enrolled. A new analysis performed in May 2013 did not show significant changes in RFS or OS duration. However, our first finding on the association between the number of invaded lymph nodes and TIL effectiveness was strengthened. The Cox model adjusted on this interaction showed for the first time a significant treatment effect when considering the overall population, both on the RFS and OS. Patients treated with TIL had a longer RFS (P = 0.023) or OS (P = 0.020). This study being with a very long followup (17 years), confirmed the association between TIL effectiveness and the number of invaded lymph nodes, indicating that a low tumor burden could be a crucial factor enhancing the curative effect of TIL in possible microscopic residual disease. Moreover, we confirmed that a prolonged survival was associated with the presence of specific TIL and a decrease in Foxp3 expression.

  6. Long-term survival estimates of cast gold inlays and onlays with their analysis of failures.

    PubMed

    Studer, S P; Wettstein, F; Lehner, C; Zullo, T G; Schärer, P

    2000-06-01

    The aim of the present study was to assess the clinical behaviour of cast gold restorations with respect to define a gold control against current and future ceramic and composite restorations. The study sample included 50 patients with 303 cast gold restorations. All restorations were cemented with a non-adhesive technique. A total of 303 restorations were evaluated clinically and radiographically using modified United States Public Health Service criteria. Restorations recorded as having an A- or a B-rating were defined as successful. Of the 303 restorations, 42 were judged as failures, which resulted in a failure rate of 13.8% for a mean observation time (+/- s.d.) of 18.7 ( +/- 9.5) years. The estimated Kaplan-Meier survival rates (s.e.) were 96.1% (+/- 1.1%) at 10 years, 87.0% (+/- 2.2%) at 20 years and 73.5% (+/- 5.4%) at 30 years. In total, biological reasons were counted 25 times in comparison to 17 technical reasons for those 42 failed cast gold restorations, with 17 secondary caries (40%) as the most common biological reason and with 13 retention losses (31%) as the most common technical reason. The endodontically treated tooth was exclusively identified as a risk factor. The restoration type (inlay versus onlay) did not influence the survival rate.

  7. Foraminiferal survival after long-term in situ experimentally induced anoxia

    NASA Astrophysics Data System (ADS)

    Langlet, D.; Geslin, E.; Baal, C.; Metzger, E.; Lejzerowicz, F.; Riedel, B.; Zuschin, M.; Pawlowski, J.; Stachowitsch, M.; Jorissen, F. J.

    2013-11-01

    Anoxia was successfully induced in four benthic chambers installed at 24 m depth on the northern Adriatic seafloor from 9 days to 10 months. To accurately determine whether benthic foraminifera can survive experimentally induced prolonged anoxia, the CellTrackerTM Green method was applied and calcareous and agglutinated foraminifera were analyzed. Numerous individuals were found living at all sampling times and at all sampling depths (to 5 cm), supported by a ribosomal RNA analysis that revealed that certain benthic foraminifera were active after 10 months of anoxia. The results show that benthic foraminifera can survive up to 10 months of anoxia with co-occurring hydrogen sulfides. However, foraminiferal standing stocks decrease with sampling time in an irregular manner. A large difference in standing stock between two cores sampled under initial conditions indicates the presence of a large spatial heterogeneity of the foraminiferal faunas. An unexpected increase in standing stocks after one month is tentatively interpreted as a reaction to increased food availability due to the massive mortality of infaunal macrofaunal organisms. After this, standing stocks decrease again in cores sampled after 2 months of anoxia to then attain a minimum in the cores sampled after 10 months. We speculate that the trend of overall decrease of standing stocks is not due to the adverse effects of anoxia and hydrogen sulfides but rather due to a continuous diminution of labile organic matter.

  8. Long-term survival of salivary streptococci on dental devices made of ethylene vinyl acetate

    PubMed Central

    Ogawa, Taiji; Yamasaki, Sayaka; Honda, Mariko; Terao, Yutaka; Kawabata, Shigetada; Maeda, Yoshinobu

    2012-01-01

    Bacterial infection associated with the use of medical or dental devices is a serious concern. Although devices made of ethylene vinyl acetate (EVA) are often used in the oral cavity, there are no established standards for their storage. We investigated bacterial survival on EVA sheets under various storage conditions to establish a standard for hygienic storage of such dental devices. Bacterial counts were evaluated, which showed a significant decrease after washing with sterilized water, mechanical brushing and rinsing, and using Mouthguard Cleaner as compared to untreated samples. In addition, no bacteria were detected on samples stored 2 days or longer in a ventilated environment, whereas they were detected for up to 14 days on samples without any cleaning stored in a closed environment. Bacterial counts for the untreated samples gradually declined, while surviving bacteria on samples treated with sterilized water and mechanical brushing showed a rapid decrease. Additionally, bacterial identification using polymerase chain reaction (PCR) revealed that Streptococcus oralis was dominantly detected on salivary samples after 14 days of storage among both two subjects. For effective hygienic storage of dental devices made of EVA, washing with sterilized water is important to remove absorbed salivary compounds along with storage in a ventilated environment. PMID:22422084

  9. Efficient long-term survival of cell grafts after myocardial infarction with thick viable cardiac tissue entirely from pluripotent stem cells

    PubMed Central

    Matsuo, Takehiko; Masumoto, Hidetoshi; Tajima, Shuhei; Ikuno, Takeshi; Katayama, Shiori; Minakata, Kenji; Ikeda, Tadashi; Yamamizu, Kohei; Tabata, Yasuhiko; Sakata, Ryuzo; Yamashita, Jun K.

    2015-01-01

    Poor engraftment of cells after transplantation to the heart is a common and unresolved problem in the cardiac cell therapies. We previously generated cardiovascular cell sheets entirely from pluripotent stem cells with cardiomyocytes, endothelial cells and vascular mural cells. Though sheet transplantation showed a better engraftment and improved cardiac function after myocardial infarction, stacking limitation (up to 3 sheets) by hypoxia hampered larger structure formation and long-term survival of the grafts. Here we report an efficient method to overcome the stacking limitation. Insertion of gelatin hydrogel microspheres (GHMs) between each cardiovascular cell sheet broke the viable limitation via appropriate spacing and fluid impregnation with GHMs. Fifteen sheets with GHMs (15-GHM construct; >1 mm thickness) were stacked within several hours and viable after 1 week in vitro. Transplantation of 5-GHM constructs (≈2 × 106 of total cells) to a rat myocardial infarction model showed rapid and sustained functional improvements. The grafts were efficiently engrafted as multiple layered cardiovascular cells accompanied by functional capillary networks. Large engrafted cardiac tissues (0.8 mm thickness with 40 cell layers) successfully survived 3 months after TX. We developed an efficient method to generate thicker viable tissue structures and achieve long-term survival of the cell graft to the heart. PMID:26585309

  10. Efficient long-term survival of cell grafts after myocardial infarction with thick viable cardiac tissue entirely from pluripotent stem cells.

    PubMed

    Matsuo, Takehiko; Masumoto, Hidetoshi; Tajima, Shuhei; Ikuno, Takeshi; Katayama, Shiori; Minakata, Kenji; Ikeda, Tadashi; Yamamizu, Kohei; Tabata, Yasuhiko; Sakata, Ryuzo; Yamashita, Jun K

    2015-11-20

    Poor engraftment of cells after transplantation to the heart is a common and unresolved problem in the cardiac cell therapies. We previously generated cardiovascular cell sheets entirely from pluripotent stem cells with cardiomyocytes, endothelial cells and vascular mural cells. Though sheet transplantation showed a better engraftment and improved cardiac function after myocardial infarction, stacking limitation (up to 3 sheets) by hypoxia hampered larger structure formation and long-term survival of the grafts. Here we report an efficient method to overcome the stacking limitation. Insertion of gelatin hydrogel microspheres (GHMs) between each cardiovascular cell sheet broke the viable limitation via appropriate spacing and fluid impregnation with GHMs. Fifteen sheets with GHMs (15-GHM construct; >1 mm thickness) were stacked within several hours and viable after 1 week in vitro. Transplantation of 5-GHM constructs (≈2 × 10(6) of total cells) to a rat myocardial infarction model showed rapid and sustained functional improvements. The grafts were efficiently engrafted as multiple layered cardiovascular cells accompanied by functional capillary networks. Large engrafted cardiac tissues (0.8 mm thickness with 40 cell layers) successfully survived 3 months after TX. We developed an efficient method to generate thicker viable tissue structures and achieve long-term survival of the cell graft to the heart.

  11. A microfluidic-based cell encapsulation platform to achieve high long-term cell viability in photopolymerized PEGNB hydrogel microspheres.

    PubMed

    Jiang, Zhongliang; Xia, Bingzhao; McBride, Ralph; Oakey, John

    2017-01-07

    Cell encapsulation within photopolymerized polyethylene glycol (PEG)-based hydrogel scaffolds has been demonstrated as a robust strategy for cell delivery, tissue engineering, regenerative medicine, and developing in vitro platforms to study cellular behavior and fate. Strategies to achieve spatial and temporal control over PEG hydrogel mechanical properties, chemical functionalization, and cytocompatibility have advanced considerably in recent years. Recent microfluidic technologies have enabled the miniaturization of PEG hydrogels, thus enabling the fabrication of miniaturized cell-laden vehicles. However, rapid oxygen diffusive transport times on the microscale dramatically inhibit chain growth photopolymerization of polyethylene glycol diacrylate (PEGDA), thus decreasing the viability of cells encapsulated within these microstructures. Another promising PEG-based scaffold material, PEG norbornene (PEGNB), is formed by a step-growth photopolymerization and is not inhibited by oxygen. PEGNB has also been shown to be more cytocompatible than PEGDA and allows for orthogonal addition reactions. The step-growth kinetics, however, are slow and therefore challenging to fully polymerize within droplets flowing through microfluidic devices. Here, we describe a microfluidic-based droplet fabrication platform that generates consistently monodisperse cell-laden water-in-oil emulsions. Microfluidically generated PEGNB droplets are collected and photopolymerized under UV exposure in bulk emulsions. In this work, we compare this microfluidic-based cell encapsulation platform with a vortex-based method on the basis of microgel size, uniformity, post-encapsulation cell viability and long-term cell viability. Several factors that influence post-encapsulation cell viability were identified. Finally, long-term cell viability achieved by this platform was compared to a similar cell encapsulation platform using PEGDA. We show that this PEGNB microencapsulation platform is capable of

  12. Long-term analysis of survival, fertility, and population growth rate of black bears in North Carolina

    USGS Publications Warehouse

    Brongo, L.L.; Mitchell, M.S.; Grand, J.B.

    2005-01-01

    We estimated survival, fertility, and realized and asymptotic population growth rates from 1981 to 2002 for a protected population of black bears (Ursus americanus) in the southern Appalachian Mountains. We used Akaike's information criterion to assess the time interval for averaging observations that was best for estimating vital rates for our study, given our yearly sample sizes. The temporal symmetry approach allowed us to directly assess population growth and to address all losses and gains to the population by using only capture data, offering an alternative to the logistically intensive collection of reproductive data. Models that averaged survival and fertility across 5- and 7-year time intervals were best supported by our data. Studies of black bear populations with annual sample sizes similar to ours should be of at least 5 years in duration to estimate vital rates reliably, and at least 10 years in duration to evaluate changes in population growth rate (??). We also hypothesized that survival would not track changes in ?? because ?? is influenced by both survival and fertility. The 5-year model supported our hypothesis, but the 7-year model did not. Where long-term dynamics of large, relatively stable bear populations are of interest, monitoring survival is likely to be sufficient for evaluating trends in ??. For rapidly changing, small populations, however, failure to incorporate fertility into assessments of ?? could be misleading. ?? 2005 American Society of Mammalogists.

  13. Superinfection exclusion and the long-term survival of honey bees in Varroa-infested colonies.

    PubMed

    Mordecai, Gideon J; Brettell, Laura E; Martin, Stephen J; Dixon, David; Jones, Ian M; Schroeder, Declan C

    2016-05-01

    Over the past 50 years, many millions of European honey bee (Apis mellifera) colonies have died as the ectoparasitic mite, Varroa destructor, has spread around the world. Subsequent studies have indicated that the mite's association with a group of RNA viral pathogens (Deformed Wing Virus, DWV) correlates with colony death. Here, we propose a phenomenon known as superinfection exclusion that provides an explanation of how certain A. mellifera populations have survived, despite Varroa infestation and high DWV loads. Next-generation sequencing has shown that a non-lethal DWV variant 'type B' has become established in these colonies and that the lethal 'type A' DWV variant fails to persist in the bee population. We propose that this novel stable host-pathogen relationship prevents the accumulation of lethal variants, suggesting that this interaction could be exploited for the development of an effective treatment that minimises colony losses in the future.

  14. Hypoplastic left heart syndrome: from comfort care to long-term survival

    PubMed Central

    Yabrodi, Mouhammad; Mastropietro, Christopher W.

    2017-01-01

    The management of hypoplastic left heart syndrome (HLHS) has changed substantially over the past four decades. In the 1970s, children with HLHS could only be provided with supportive care. As a result, most of these unfortunate children died within the neonatal period. The advent of the Norwood procedure in the early 1980s has changed the prognosis for these children, and the majority now undergoing a series of three surgical stages that can support survival beyond the neonatal period and into early adulthood. This review will focus on the Norwood procedure and the other important innovations of the last half century that have improved our outlook toward children born with HLHS. PMID:27701379

  15. Case of congenital short small intestine: survival with use of long-term parenteral feeding.

    PubMed

    Dorney, S F; Byrne, W J; Ament, M E

    1986-03-01

    Isolated congenital short small intestine is a rare anomaly. Of six (one male, five females) previously reported cases, four died in infancy from intractable diarrhea. We report the case of 7-year-old boy with this syndrome in whom a 2-year period of parenteral feeding at home allowed normal weight gain, growth, and development while intestinal adaptation occurred. Parenteral feeding was discontinued at age 2 1/3 years, and for the past 5 years his weight has remained between the tenth and 25th percentiles and his stature between the 25th and 50th percentiles. His development has been normal and he functions at or above grade level at school. Coefficient of fat absorption has increased from 54% to 81%. Vitamin B12 absorption has improved but has not normalized. He remains lactose intolerant. We believe his survival, growth, and development would have been compromised if he had not received a prolonged period of parenteral feeding.

  16. Superinfection exclusion and the long-term survival of honey bees in Varroa-infested colonies

    PubMed Central

    Mordecai, Gideon J; Brettell, Laura E; Martin, Stephen J; Dixon, David; Jones, Ian M; Schroeder, Declan C

    2016-01-01

    Over the past 50 years, many millions of European honey bee (Apis mellifera) colonies have died as the ectoparasitic mite, Varroa destructor, has spread around the world. Subsequent studies have indicated that the mite's association with a group of RNA viral pathogens (Deformed Wing Virus, DWV) correlates with colony death. Here, we propose a phenomenon known as superinfection exclusion that provides an explanation of how certain A. mellifera populations have survived, despite Varroa infestation and high DWV loads. Next-generation sequencing has shown that a non-lethal DWV variant ‘type B' has become established in these colonies and that the lethal ‘type A' DWV variant fails to persist in the bee population. We propose that this novel stable host-pathogen relationship prevents the accumulation of lethal variants, suggesting that this interaction could be exploited for the development of an effective treatment that minimises colony losses in the future. PMID:26505829

  17. Divine Love and Deep Connections: A Long-Term Followup of Patients Surviving Cardiac Surgery

    PubMed Central

    Ai, Amy L.; Hall, Daniel E.

    2011-01-01

    We examined experiencing divine love as an indicator of affective spiritual growth in a prospective cohort of 200 patients surviving cardiac surgery. These patients previously completed two-wave preoperative interviews when standardized cardiac surgery data were also collected. The information included left ventricular ejection fraction, New York Heart Association Classification, baseline health (physical and mental), optimism, hope, religiousness, prayer coping, religious/spiritual coping, and demographics. We then measured divine love at 900 days postoperatively. Hierarchical linear regression indicated the direct effect of positive religious coping on experiences of divine love, controlling for other key variables. Postoperatively perceived spiritual support was entered at the final step as an explanatory factor, which appeared to mediate the coping effect. None of the other faith factors predicted divine love. Further research regarding divine love and spiritual support may eventually guide clinical attempts to support patients' spiritual growth as an independently relevant outcome of cardiac surgery. PMID:21748012

  18. Effects of moisture content on long-term survival and regrowth of bacteria in wastewater sludge.

    PubMed Central

    Yeager, J G; Ward, R L

    1981-01-01

    The effects of moisture content on the survival and regrowth of seeded and indigenous enteric bacteria in raw sludge were determined. Cultures of six strains of fecally associated bacteria grown in sterilized, liquid sludge (5% solids) were all quite stable at this moisture level for over 90 days at 21 degrees C. When the moisture content of the sludge containing these organisms was reduced by evaporation and the samples were stored at 21 degrees C for extended periods, bacterial inactivation rates were generally proportional to the moisture losses of the samples. A dramatic reversal in this effect was observed in samples containing more than 90% solids. In this dried sludge, every bacterial species studied except Proteus mirabilis was found to be extremely stable. Bacteria indigenous to sludge were also found to survive for long periods in dried sludge. Regrowth of bacterial isolates in sterilized raw sludge was found to occur readily at 37 degrees C in samples containing less than or equal to 75% solids, but no growth was observed in samples with greater than or equal to 85% solids. Some growth, but to less than saturation densities, occurred with 80% solids. Growth of seeded Salmonella typhimurium was also found to occur in the presence of indigenous organisms in both liquid and dewatered raw sludges. However, the population density attained was well below that found in sterilized samples of the same sludges. In addition, the number of salmonellae dropped below detectable limits within a few days in sludges containing viable indigenous organisms, whereas little decrease occurred during this time with salmonellae grown in previously sterilized sludges. PMID:6789764

  19. Long-Term Survival and Risk of Second Cancers After Radiotherapy for Cervical Cancer

    SciTech Connect

    Ohno, Tatsuya; Kato, Shingo; Sato, Shinichiro; Fukuhisa, Kenjiro; Nakano, Takashi; Tsujii, Hirohiko; Arai, Tatsuo

    2007-11-01

    Purpose: To evaluate the risk of second cancers after cervical cancer treated with radiotherapy for Asian populations. Methods and Materials: We reviewed 2,167 patients with cervical cancer undergoing radiotherapy between 1961 and 1986. Intracavitary brachytherapy was performed with high-dose rate source (82%) or low-dose rate source (12%). Relative risk (RR), absolute excess risk (AR), and cumulative risk of second cancer were calculated using the Japanese disease expectancy table. For 1,031 patients, the impact of smoking habit on the increasing risk of second cancer was also evaluated. Results: The total number of person-years of follow-up was 25,771, with 60 patients being lost to follow-up. Among the 2,167 patients, 1,063 (49%) survived more than 10 years. Second cancers were observed in 210 patients, representing a significant 1.2-fold risk (95% confidence interval [CI], 1.1-1.4) of developing second cancer compared with the general population, 1.6% excess risk per person per decade of follow-up, and elevating cumulative risk up to 23.8% (95% CI, 20.3-27.3) at 30 years after radiotherapy. The RR of second cancer was 1.6-fold for patients with the smoking habit and 1.4-fold for those without. Conclusions: Small but significant increased risk of second cancer was observed among Japanese women with cervical cancer mainly treated with high-dose rate brachytherapy. Considering the fact that about half of the patients survived more than 10 years, the benefit of radiotherapy outweighs the risk of developing second cancer.

  20. A fluctuating thermal regime improves long-term survival of quiescent prepupal Megachile rotundata (Hymenoptera: Megachilidae).

    PubMed

    Rinehart, Joseph P; Yocum, George D; Kemp, William P; Greenlee, Kendra J

    2013-06-01

    The alfalfa leafcutting bee Megachile rotundata (F.) is the primary pollinator for alfalfa seed production. Under standard management conditions, the alfalfa leafcutting bee develops to the diapausing prepupal stage under field conditions, after which they are cold-stored at a static temperature until the following spring, when temperatures are raised and development resumes. We have assessed the effects of a fluctuating thermal regime (FTR) during overwintering cold storage, where bees were exposed to a daily 1 h pulse of 20 degrees C, and compared viability and insect quality to bees stored under a static thermal regime. Our results demonstrate that implementing an FTR protocol dramatically increases the survival of cold-stored alfalfa leafcutting bees, effectively extending their shelf-life into the subsequent growing season. These findings could substantially ameliorate significant obstacles that restrict the more widespread use of this important pollinator, such as the biological constraints that restrict its use in early blooming crops, and yearly fluctuations in bee prices that add significant financial uncertainty to end users. This study also strengthens a growing body of evidence that indicates FTR protocols are superior to static thermal regime protocols for insect cold storage.

  1. Perioperative treatment options in resectable pancreatic cancer - how to improve long-term survival

    PubMed Central

    Sinn, Marianne; Bahra, Marcus; Denecke, Timm; Travis, Sue; Pelzer, Uwe; Riess, Hanno

    2016-01-01

    Surgery remains the only chance of cure for pancreatic cancer, but only 15%-25% of patients present with resectable disease at the time of primary diagnosis. Important goals in clinical research must therefore be to allow early detection with suitable diagnostic procedures, to further broaden operation techniques and to determine the most effective perioperative treatment of either chemotherapy and/or radiation therapy. More extensive operations involving extended pancreatectomy, portal vein resection and pancreatic resection in resectable pancreatic cancer with limited liver metastasis, performed in specialized centers seem to be the surgical procedures with a possible impact on survival. After many years of stagnation in pharmacological clinical research on advanced pancreatic ductal adenocarcinomas (PDAC) - since the approval of gemcitabine in 1997 - more effective cytotoxic substances (nab-paclitaxel) and combinations (FOLFIRINOX) are now available for perioperative treatment. Additionally, therapies with a broader mechanism of action are emerging (stroma depletion, immunotherapy, anti-inflammation), raising hopes for more effective adjuvant and neoadjuvant treatment concepts, especially in the context of “borderline resectability”. Only multidisciplinary approaches including radiology, surgery, medical and radiation oncology as the backbones of the treatment of potentially resectable PDAC may be able to further improve the rate of cure in the future. PMID:26989460

  2. Survival of a Psychrophilic Marine Vibrio Under Long-Term Nutrient Starvation 1

    PubMed Central

    Novitsky, James A.; Morita, Richard Y.

    1977-01-01

    Ant-300, a psychrophilic marine vibrio isolated from the surface water of the Antarctic convergence, was starved for periods of more than 1 year. During the first week of starvation, cell numbers increased from 100 to 800% of the initial number of cells. Fifty percent of the starved cells remained viable for 6 to 7 weeks while a portion of the population remained viable for more than 1 year. During the first 2 days of starvation, the endogenous respiration of the cells decreased over 80%. After 7 days, respiration had been reduced to 0.0071% total carbon respired per hour and remained constant thereafter. After 6 weeks of starvation, 46% of the cellular deoxyribonucleic acid had been degraded. Observation of the cellular deoxyribonucleic acid with Feulgen staining before starvation showed the average number of nuclear bodies per cell varied from 1.44 to 4.02 depending on the age of the culture. A linear relationship was found between the number of nuclear bodies per cell and the increase in cell numbers upon starvation. Our data suggest that Ant-300 is capable of surviving long periods of time with little or no nutrients and is therefore well adapted for the sparse nutrient conditions of the colder portions of the open ocean. PMID:16345219

  3. Association between urinary sodium, creatinine, albumin, and long-term survival in chronic kidney disease.

    PubMed

    McQuarrie, Emily P; Traynor, Jamie P; Taylor, Alison H; Freel, E Marie; Fox, Jonathan G; Jardine, Alan G; Mark, Patrick B

    2014-07-01

    Dietary sodium intake is associated with hypertension and cardiovascular risk in the general population. In patients with chronic kidney disease, sodium intake has been associated with progressive renal disease, but not independently of proteinuria. We studied the relationship between urinary sodium (UNa) excretion and UNa to creatinine ratio and mortality or requirement for renal replacement therapy in chronic kidney disease. Adult patients attending a renal clinic who had ≥1 24-hour UNa measurement were identified. Twenty-four-hour UNa measures were collected and UNa to creatinine ratio calculated. Time to renal replacement therapy or death was recorded. Four hundred twenty-three patients were identified with mean estimated glomerular filtration rate of 48 mL/min per 1.73 m(2). Ninety patients required renal replacement therapy and 102 patients died. Mean slope decline in estimated glomerular filtration rate was -2.8 mL/min per 1.73 m(2) per year. Median follow-up was 8.5 years. Patients who died or required renal replacement therapy had significantly higher UNa excretion and UNa to creatinine ratio, but the association with these parameters and poor outcome was not independent of renal function, age, and albuminuria. When stratified by albuminuria, UNa to creatinine ratio was a significant cumulative additional risk for mortality, even in patients with low-level albuminuria. There was no association between low UNa and risk, as observed in some studies. This study demonstrates an association between UNa excretion and mortality in chronic kidney disease, with a cumulative relationship between sodium excretion, albuminuria, and reduced survival. These data support reducing dietary sodium intake in chronic kidney disease, but additional study is required to determine the target sodium intake.

  4. The long-term survival in adrenocortical carcinoma with active surgical management and use of monitored mitotane.

    PubMed

    Wängberg, B; Khorram-Manesh, A; Jansson, S; Nilsson, B; Nilsson, O; Jakobsson, C E; Lindstedt, S; Odén, A; Ahlman, H

    2010-03-01

    Adrenocortical carcinoma (ACC) is a rare tumour disease with sinister prognosis also after attempts to radical surgery; better prognosis is seen for low-stage tumours. Adjuvant treatment with the adrenolytic drug mitotane has been attempted, but not proven to prevent from recurrence. The drug may offer survival advantage in case of recurrence. The aim of this single-centre study (1979-2007) of 43 consecutive patients was to evaluate the long-term survival after active surgical treatment combined with monitored mitotane (to reduce side effects of the drug). The series is unique, since all patients were offered a period of mitotane as adjuvant or palliative treatment; six patients refused mitotane. Despite a high proportion of high-stage tumours (67%), the complete resection rate was high (77%). The disease-specific 5-year survival was high (64.1%); very high for patients with low-stage tumours without evident relation to mitotane levels. Patients with high-stage tumours had a clear survival advantage with mitotane levels above a threshold of 14 mg/l in serum. The hazard ratio for patients with high mitotane levels versus all patients indicates a significant effect of the drug. The results indicate that adjuvant mitotane may be the standard of care for patients with high-stage ACC after complete resection.

  5. Long-term survival and late deaths after hematopoietic cell transplantation for primary immunodeficiency diseases and inborn errors of metabolism.

    PubMed

    Eapen, Mary; Ahn, Kwang Woo; Orchard, Paul J; Cowan, Morton J; Davies, Stella M; Fasth, Anders; Hassebroek, Anna; Ayas, Mouhab; Bonfim, Carmem; O'Brien, Tracey A; Gross, Thomas G; Horwitz, Mitchell; Horwitz, Edwin; Kapoor, Neena; Kurtzberg, Joanne; Majhail, Navneet; Ringden, Olle; Szabolcs, Paul; Veys, Paul; Baker, K Scott

    2012-09-01

    It is uncertain whether late mortality rates after hematopoietic cell transplantation for severe combined immunodeficiency (SCID), non-SCID primary immunodeficiency diseases (non-SCID PIDD), and inborn errors of metabolism (IEM) return to rates observed in the general population, matched for age, sex, and nationality. We studied patients with SCID (n = 201), non-SCID PIDD (n = 405), and IEM (n = 348) who survived for at least 2 years after transplantation with normal T cell function (SCID) or >95% donor chimerism (non-SCID PIDD and IEM). Importantly, mortality rate was significantly higher in these patients compared with the general population for several years after transplantation. The rate decreased toward the normal rate in patients with SCID and non-SCID PIDD beyond 6 years after transplantation, but not in patients with IEM. Active chronic graft-versus-host disease at 2 years was associated with increased risk of late mortality for all diseases (hazard ratio [HR], 1.87; P = .05). In addition, late mortality was higher in patients with non-SCID PIDD who received T cell-depleted grafts (HR 4.16; P = .007) and in patients with IEM who received unrelated donor grafts (HR, 2.72; P = .03) or mismatched related donor grafts (HR, 3.76; P = .01). The finding of higher mortality rates in these long-term survivors for many years after transplantation confirms the need for long-term surveillance.

  6. Significance of anti-HLA and donor-specific antibodies in long-term renal graft survival.

    PubMed

    Saidman, S

    2007-04-01

    Numerous studies have demonstrated an association of posttransplant HLA antibodies with decreased long-term graft survival. The presence of C4d deposition in these cases supports the hypothesis that antibody and complement deposition are involved in the pathogenesis of graft failure. Development of HLA antibodies may predate the clinical manifestation of chronic rejection (CR). However, frequency of donor-specific antibody is low when all patients are screened regardless of their graft function, and it may be more valuable to look for antibody only in patients with mild dysfunction. Effective treatment for CR has not been identified, although increased immunosuppression has been shown to decrease antibody levels and stabilize graft function. Many patients have been identified with good graft function despite the presence of circulating donor-specific HLA antibody. Additional studies focusing on the mechanism behind the apparent protection from the detrimental effects of antibody in such patients are needed.

  7. Anti-PD-1 Blockade and Stereotactic Radiation Produce Long-Term Survival in Mice With Intracranial Gliomas

    SciTech Connect

    Zeng, Jing; See, Alfred P.; Phallen, Jillian; Jackson, Christopher M.; Belcaid, Zineb; Ruzevick, Jacob; Durham, Nicholas; Meyer, Christian; Harris, Timothy J.; Albesiano, Emilia; Pradilla, Gustavo; Ford, Eric; Wong, John; Hammers, Hans-Joerg; Mathios, Dimitris; Tyler, Betty; Brem, Henry; Tran, Phuoc T.; Pardoll, Drew; Drake, Charles G.; and others

    2013-06-01

    Purpose: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, and radiation is one of the main treatment modalities. However, cure rates remain low despite best available therapies. Immunotherapy is a promising modality that could work synergistically with radiation, which has been shown to increase antigen presentation and promote a proinflammatory tumor microenvironment. Programmed-death-1 (PD-1) is a surface receptor expressed on activated and exhausted T cells, which mediate T cell inhibition upon binding with its ligand PD-L1, expressed on many tumor types including human GBMs. We tested the combination of anti-PD-1 immunotherapy with stereotactic radiosurgery in a mouse orthotopic GBM model. Methods and Materials: We performed intracranial implantation of mouse glioma cell line GL261 transfected with luciferase into C57BL/6 mice. Mice were stratified into 4 treatment groups: (1) control; (2) radiation only; (3) anti-PD-1 antibody only; and (4) radiation plus anti-PD-1 antibody. Overall survival was quantified. The mice were killed on day 21 after implantation to assess immunologic parameters in the brain/tumor, cervical lymph nodes, and spleen. Results: Improved survival was demonstrated with combination anti-PD-1 therapy plus radiation compared with either modality alone: median survival was 25 days in the control arm, 27 days in the anti-PD-1 antibody arm, 28 days in the radiation arm, and 53 days in the radiation plus anti-PD-1 therapy arm (P<.05 by log-rank Mantle-Cox). Long-term survival was seen only in the combined treatment arm, with a fraction (15%-40%) of animals alive at day 180+ after treatment. Immunologic data on day 21 after implantation showed increased tumor infiltration by cytotoxic T cells (CD8+/interferon-γ+/tumor necrosis factor-α+) and decreased regulatory T cells (CD4+/FOXP3) in the combined treatment group compared with the single modality arms. Conclusions: The combination of PD-1 blockade and localized

  8. Biochemical Response to Androgen Deprivation Therapy Before External Beam Radiation Therapy Predicts Long-term Prostate Cancer Survival Outcomes

    SciTech Connect

    Zelefsky, Michael J.; Gomez, Daniel R.; Polkinghorn, William R.; Pei, Xin; Kollmeier, Marisa

    2013-07-01

    Purpose: To determine whether the response to neoadjuvant androgen deprivation therapy (ADT) defined by a decline in prostate-specific antigen (PSA) to nadir values is associated with improved survival outcomes after external beam radiation therapy (EBRT) for prostate cancer. Methods and Materials: One thousand forty-five patients with localized prostate cancer were treated with definitive EBRT in conjunction with neoadjuvant and concurrent ADT. A 6-month course of ADT was used (3 months during the neoadjuvant phase and 2 to 3 months concurrently with EBRT). The median EBRT prescription dose was 81 Gy using a conformal-based technique. The median follow-up time was 8.5 years. Results: The 10-year PSA relapse-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 74.3%, compared with 57.7% for patients with higher PSA nadir values (P<.001). The 10-year distant metastases-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 86.1%, compared with 78.6% for patients with higher PSA nadir values (P=.004). In a competing-risk analysis, prostate cancer-related deaths were also significantly reduced among patients with pre-radiation therapy PSA nadirs of <0.3 ng/mL compared with higher values (7.8% compared with 13.7%; P=.009). Multivariable analysis demonstrated that the pre-EBRT PSA nadir value was a significant predictor of long-term biochemical tumor control, distant metastases-free survival, and cause-specific survival outcomes. Conclusions: Pre-radiation therapy nadir PSA values of ≤0.3 ng/mL after neoadjuvant ADT were associated with improved long-term biochemical tumor control, reduction in distant metastases, and prostate cancer-related death. Patients with higher nadir values may require alternative adjuvant therapies to improve outcomes.

  9. Long-term results of the GIMEMA VEL-03-096 trial in MM patients receiving VTD consolidation after ASCT: MRD kinetics' impact on survival.

    PubMed

    Ferrero, S; Ladetto, M; Drandi, D; Cavallo, F; Genuardi, E; Urbano, M; Caltagirone, S; Grasso, M; Rossini, F; Guglielmelli, T; Cangialosi, C; Liberati, A M; Callea, V; Carovita, T; Crippa, C; De Rosa, L; Pisani, F; Falcone, A P; Pregno, P; Oliva, S; Terragna, C; Musto, P; Passera, R; Boccadoro, M; Palumbo, A

    2015-03-01

    Polymerase chain reaction (PCR)-based minimal residual disease (MRD) analysis is a useful prognostic tool in multiple myeloma (MM), although its long-term impact still needs to be addressed. This report presents the updated results of the GIMEMA-VEL-03-096 trial. Thirty-nine MM patients receiving bortezomib-thalidomide-dexamethasone after autologous transplantation were monitored for MRD by both nested and real-time quantitative-PCR until relapse. Our data confirm the strong impact of MRD on survival: overall survival was 72% at 8 years median follow-up for patients in major MRD response versus 48% for those experiencing MRD persistence (P=0.041). In addition, MRD kinetics resulted predictive for relapse: indeed median remission duration was not reached for patients in major MRD response, 38 months for those experiencing MRD reappearance and 9 months for patients with MRD persistence (P<0.001). Moreover: (1) 26 patients achieving major MRD response (67%) benefit of excellent disease control (median TNT: 42 months); (2) MRD reappearance heralds relapse, with a TNT comparable to that of MRD persistence (9 versus 10 months, P=0.706); (3) the median lag between MRD reappearance and need for salvage treatment is 9 months. These results suggest the usefulness of a long-term MRD monitoring in MM patients and the need for maintenance or pre-emptive treatments ensuring durable responses.

  10. Ribozyme rescue of photoreceptor cells in P23H transgenic rats: long-term survival and late-stage therapy.

    PubMed

    LaVail, M M; Yasumura, D; Matthes, M T; Drenser, K A; Flannery, J G; Lewin, A S; Hauswirth, W W

    2000-10-10

    Ribozyme-directed cleavage of mutant mRNAs appears to be a potentially effective therapeutic measure for dominantly inherited diseases. We previously demonstrated that two ribozymes targeted to the P23H mutation in rhodopsin slow photoreceptor degeneration in transgenic rats for up to 3 months of age when injected before significant degeneration at postnatal day (P) 15. We now have explored whether ribozyme rescue persists at older ages, and whether ribozymes are effective when injected later in the degeneration after significant photoreceptor cell loss. Recombinant adeno-associated virus (rAAV) vectors incorporating a proximal bovine rod opsin promoter were used to transfer either hairpin or hammerhead ribozyme genes to photoreceptors. For the study of long-term survival, rAAV was administered by subretinal injection at P15, and the rats were allowed to live up to 8 months of age. For the study of late-stage gene transfer, rAAV was administered at P30 or P45, when 40-45% of the photoreceptors already had degenerated. Eyes were examined functionally by the electroretinogram and structurally by morphometric analysis. When injected at P15, expression of either ribozyme markedly slowed the rate of photoreceptor degeneration for at least 8 months and resulted in significantly greater electroretinogram amplitudes at least up to P180. When injected at P30 or P45, virtually the same number of photoreceptors survived at P130 as when injected at P15. Ribozyme rescue appears to be a potentially effective, long-term therapy for autosomal dominant retinal degeneration and is highly effective even when the gene transfer is done after significant photoreceptor cell loss.

  11. Long-term survival outcomes of reduced-intensity allogeneic or autologous transplantation in relapsed grade 3 follicular lymphoma

    PubMed Central

    Klyuchnikov, Evgeny; Bacher, Ulrike; Ahn, Kwang Woo; Carreras, Jeanette; Kröger, Nicolaus M.; Hari, Parameswaran N.; Ku, Grace H.; Ayala, Ernesto; Chen, Andy I.; Chen, Yi-Bin; Cohen, Jonathon B.; Freytes, César O.; Gale, Robert Peter; Kamble, Rammurti T.; Kharfan-Dabaja, Mohamed A.; Lazarus, Hillard M.; Martino, Rodrigo; Mussetti, Alberto; Savani, Bipin N.; Schouten, Harry C.; Usmani, Saad Z.; Wiernik, Peter H.; Wirk, Baldeep; Smith, Sonali M.; Sureda, Anna; Hamadani, Mehdi

    2015-01-01

    Grade-3 follicular lymphoma (FL) has aggressive clinical behavior. To evaluate the optimal first transplantation approach in relapsed/refractory grade-3 FL patients, we compared the long-term outcomes after allogeneic (allo-) vs. autologous hematopoietic cell transplantation (auto-HCT) in the rituximab-era. A total of 197 patients undergoing first RIC allo-HCT or first auto-HCT during 2000-2012 were included. Rituximab-naïve patients were excluded. Allo-HCT recipients were younger; more heavily pretreated, and had a longer interval between diagnosis and HCT. The 5-year probabilities of non-relapse mortality (NRM), relapse/progression, progression-free survival (PFS) and overall survival (OS) for auto-HCT vs. allo-HCT groups were 4% vs. 27% (p<0.001); 61% vs. 20% (p<0.001); 36% vs. 51% (p=0.07) and 59% vs. 54% (p=0.7), respectively. On multivariate analysis auto-HCT was associated with reduced risk of NRM (RR=0.20; p=0.001). Within the first 11months post-HCT auto- and allo-HCT had similar risks of relapse/progression and PFS. Beyond 11months, auto-HCT was associated with higher risk of relapse/progression (RR=21.3; p=0.003) and inferior PFS (RR=3.2; p=0.005). In the first 24 months post-HCT, auto-HCT was associated with improved OS (RR=0.42; p=0.005), but in long-time survivors (beyond 24 months) it was associated with inferior OS (RR=3.6; p=0.04). RIC allo-HCT as the first transplant approach can provide improved PFS and OS, in long-term survivors. PMID:26437062

  12. Giant aorto-pulmonary collaterals in pulmonary atresia and ventricular septal defect: long-term survival in unoperated adults.

    PubMed

    Spaziani, Gaia; Favilli, Silvia; Fonda, Claudio; Chiappa, Enrico

    2013-08-01

    The association of pulmonary atresia and ventricular septal defect (PA/VSD) can be considered the most severe form of tetralogy of Fallot. The main feature of this congenital heart disease is represented by discontinuity between the right ventricle and pulmonary trunk or its branches; the anatomy of central pulmonary arteries is often abnormal, consequently the type and the amount of sources of pulmonary blood flow are variable. Due to evolution in surgical techniques, definitive correction is now also considered in more complex cases. A small rate of unoperated patients with PA/VSD can survive until adulthood and the arterial blood supply to the lungs, provided by major aorto-pulmonary collateral arteries (MAPCAs), is one of the main determinants of survival. We report two unoperated cases of PA/VSD and MAPCAs with long-term survival. Giant MAPCAs can occasionally be found by chest radiography in adults with unrepaired PA/VSD. Moreover, non-invasive assessment of the pulmonary arterial bed with computer tomography or MRI is helpful in these patients during follow-up. Finally, we discuss the use of oral anticoagulants and/or 5-phosphodiesterase inhibitors in these patients.

  13. Growth advantage in stationary-phase (GASP) phenotype in long-term survival strains of Geobacter sulfurreducens.

    PubMed

    Helmus, Ruth A; Liermann, Laura J; Brantley, Susan L; Tien, Ming

    2012-01-01

    Geobacter sulfurreducens exists in the subsurface and has been identified in sites contaminated with radioactive metals, consistent with its ability to reduce metals under anaerobic conditions. The natural state of organisms in the environment is one that lacks access to high concentrations of nutrients, namely electron donors and terminal electron acceptors (TEAs). Most studies have investigated G. sulfurreducens under high-nutrient conditions or have enriched for it in environmental systems via acetate amendments. We replicated the starvation state through long-term batch culture of G. sulfurreducens, where both electron donor and TEA were scarce. The growth curve revealed lag, log, stationary, death, and survival phases using acetate as electron donor and either fumarate or iron(III) citrate as TEA. In survival phase, G. sulfurreducens persisted at a constant cell count for as long as 23 months without replenishment of growth medium. Geobacter sulfurreducens demonstrated an ability to acquire a growth advantage in stationary-phase phenotype (GASP), with strains derived from subpopulations from death- or survival phase being able to out-compete mid-log-phase populations when co-cultured. The molecular basis for GASP was not because of any detectable mutation in the rpoS gene (GSU1525) nor because of a mutation in a putative homolog to Escherichia coli lrp, GSU3370.

  14. Short-Term and Long-Term Survival and Virulence of Legionella pneumophila in the Defined Freshwater Medium Fraquil

    PubMed Central

    Mendis, Nilmini; McBride, Peter; Faucher, Sébastien P.

    2015-01-01

    Legionella pneumophila (Lp) is the etiological agent responsible for Legionnaires’ disease, a potentially fatal pulmonary infection. Lp lives and multiplies inside protozoa in a variety of natural and man-made water systems prior to human infection. Fraquil, a defined freshwater medium, was used as a highly reproducible medium to study the behaviour of Lp in water. Adopting a reductionist approach, Fraquil was used to study the impact of temperature, pH and trace metal levels on the survival and subsequent intracellular multiplication of Lp in Acanthamoeba castellanii, a freshwater protozoan and a natural host of Legionella. We show that temperature has a significant impact on the short- and long-term survival of Lp, but that the bacterium retains intracellular multiplication potential for over six months in Fraquil. Moreover, incubation in Fraquil at pH 4.0 resulted in a rapid decline in colony forming units, but was not detrimental to intracellular multiplication. In contrast, variations in trace metal concentrations had no impact on either survival or intracellular multiplication in amoeba. Our data show that Lp is a resilient bacterium in the water environment, remaining infectious to host cells after six months under the nutrient-deprived conditions of Fraquil. PMID:26406895

  15. Achieving college student possible selves: navigating the space between commitment and achievement of long-term identity goals.

    PubMed

    Pizzolato, Jane Elizabeth

    2006-01-01

    This study explores the possible-self construction and achievement process in students of color from low-income communities by investigating these processes in 28 college students. Findings suggest that while parental encouragement of college aspirations may affect age at which the college student possible self is constructed and expectancy level, development of schematic possible selves is more crucial to achievement of possible-self goals. Furthermore, findings point out a need to include conceptual schemas, in addition to procedural schemas, as potential predictors of possible-self achievement.

  16. Photo-induced electrochemical anodization of p-type silicon: achievement and demonstration of long term surface stability.

    PubMed

    Dhanekar, Saakshi; Islam, S S; Harsh

    2012-06-15

    Surface stability is achieved and demonstrated by porous silicon (PS) fabricated using a wavelength-dependent photo-electrochemical (PEC) anodization technique. During anodization, the photon flux for all wavelengths was kept constant while only the effect of light wavelength on the surface morphology of PS was investigated. PS optical sensors were realized, characterized and tested using a photoluminescence (PL) quenching technique. An aliphatic chain of alcohols (methanol to n-octanol) was detected in the range of 10-200 ppm. Long term surface stability was observed from samples prepared under red (750-620 nm) and green illumination (570-495 nm), where the PL quenching cycles evoke the possibility of using PS for stable sensor device applications. This study provides a route for preparing highly sensitive organic vapour sensors with a precise selection of the fabrication parameters and demonstrating their prolonged performance.

  17. Effect of positive surgical margins on biochemical failure, biochemical recurrence-free survival, and overall survival after radical prostatectomy: median long-term results.

    PubMed

    Huri, Emre; Aydogmus, Yasin; Doluoglu, Omer Gokhan; Dadali, Mumtaz; Karakan, Tolga; Emir, Levent; Germiyanoglu, Cankon

    2014-10-01

    The aim of this study was to investigate the median long-term effects of positive surgical margin (PSM) and other prognostic factors on biochemical recurrence-free survival, overall survival, and biochemical failure in patients who underwent radical prostatectomy. Our study included 121 patients with pT2-3N0 disease treated between March 2006 and August 2012. The patients were divided into two groups: those with PSM and those with negative surgical margin (NSM). We analyzed the age, clinical and pathological stages, preoperative and postoperative Gleason scores, duration of the follow-up, adjuvant chemo-/radiotherapy, biochemical failure, biochemical recurrence-free survival, and overall survival in these patients. PSM was found in 25 (20%) patients, whereas 96 patients had NSM. The median follow-up time was 46.6 months (range 12-72 months) for the PSM group and 48.3 months (range 7-149 months) for the NSM group. The biochemical failure rate was 24% in the PSM group and 8.3% in the NSM group (p = 0.029). The biochemical recurrence-free survival was found as 76% in the PSM group and 91.7% in the NSM group. The difference between the groups was not statistically significant (p = 0.06). The overall survival was 100% in both groups. The surgical margins of the radical prostatectomy material is an important pathological indicator for biochemical failure at mid long-term follow-up. We did not find any effect of PSM on overall survival or biochemical recurrence-free survival.

  18. Long-term survival after endoscopic resection for early gastric cancer in the remnant stomach: comparison with radical surgery

    PubMed Central

    Yamashina, Takeshi; Uedo, Noriya; Dainaka, Katsuyuki; Aoi, Kenji; Matsuura, Noriko; Ito, Takashi; Fujii, Mototsugu; Kanesaka, Takashi; Yamamoto, Sachiko; Akasaka, Tomofumi; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Ishihara, Ryu; Kishi, Kentaro; Fujiwara, Yoshiyuki; Iishi, Hiroyasu

    2015-01-01

    Background Endoscopic resection (ER) has recently become standard treatment, even for early gastric cancer (EGC) in the remnant stomach. We aimed to compare long-term survival after ER versus radical surgery for EGC in the remnant stomach. Methods We retrospectively compared overall and cause-specific survival of patients who had undergone ER or radical surgery for EGC in the remnant stomach from 1998 to 2012. Results During the study period, 32 patients with intramucosal (M), two with shallow submucosal (SM1) and eight with deep submucosal (SM2) cancers had undergone ER (ER group) whereas six with M and seven with SM2 cancers had undergone surgery (surgery group). All patients were followed up for a median of 60 months; during follow up, 15 patients died, including three in the ER group with SM2 cancer who died of gastric cancer. The overall 5-year survival rates of M-SM1 and SM2 cancer patients in the ER and surgery groups were 89%, 48%, 80%, and 67%, respectively (P=0.079). The disease-specific 5-year survival rates of M-SM1 and SM2 cancer patients in the ER and surgery groups were 100%, 48%, 100%, and 100%, respectively (P=0.000). Operation time and hospital stay were significantly shorter in the ER than the surgery group (P<0.001). Grade 2 perforation occurred in two patients in the ER group and Grade 3 anastomotic leakage in two patients in the surgery group. Conclusion ER provides excellent outcomes, comparable with those of radical surgery, in patients with M-SM1 gastric cancer in the remnant stomach; however, patients with SM2 cancer require radical surgery. PMID:25608929

  19. FBLN4 as candidate gene associated with long-term and short-term survival with primary glioblastoma

    PubMed Central

    Li, Fubin; Li, Yiping; Zhang, Kewei; Li, Ye; He, Ping; Liu, Yujia; Yuan, Hongyan; Lu, Honghua; Liu, Jinxiang; Che, Songtian; Li, Zhenju; Bie, Li

    2017-01-01

    Background Glioblastoma multiforme (GBM) is the most common malignant and lethal type of primary central nervous system tumor in humans. In spite of its high lethality, a small percentage of patients have a relatively good prognosis, with median survival times of 36 months or longer. The identification of clinical subsets of GBM associated with distinct molecular genetic profiles has made it possible to design therapies tailored to treat individual patients. Methods We compared microarray data sets from long-term survivors (LTSs) and short-term survivors (STSs) to screen for prognostic biomarkers in GBM patients using the WebArrayDB platform. We focused on FBLN4, IGFBP-2, and CHI3L1, all members of a group of 10 of the most promising, differentially regulated gene candidates. Using formalin-fixed paraffin-embedded GBM samples, we corroborated the relationship between these genes and patient outcomes using methylation-specific polymerase chain reaction (PCR) for MGMT methylation status and quantitative reverse transcription PCR for expression of these genes. Results Expression levels of the mRNAs of these 3 genes were higher in the GBM samples than in normal brain samples and these 3 genes were significantly upregulated in STSs compared to the levels in LTS samples (P<0.01). Furthermore, Kaplan–Meier analysis showed that the expression patterns of FBLN4 and IGFBP-2 serve as independent prognostic indicators for overall survival (P<0.01 and P<0.05, respectively). Conclusion To our knowledge, this is the first report describing FBLN4 as a prognostic factor for GBM patient survival, demonstrating that increased GBM survival time correlates with decreased FBLN4 expression. Understanding FBLN4 expression patterns could aid in the creation of powerful tools to predict clinical prognoses of GBM patients. PMID:28144153

  20. Long-term survival outcomes of reduced-intensity allogeneic or autologous transplantation in relapsed grade 3 follicular lymphoma.

    PubMed

    Klyuchnikov, E; Bacher, U; Woo Ahn, K; Carreras, J; Kröger, N M; Hari, P N; Ku, G H; Ayala, E; Chen, A I; Chen, Y-B; Cohen, J B; Freytes, C O; Gale, R P; Kamble, R T; Kharfan-Dabaja, M A; Lazarus, H M; Martino, R; Mussetti, A; Savani, B N; Schouten, H C; Usmani, S Z; Wiernik, P H; Wirk, B; Smith, S M; Sureda, A; Hamadani, M

    2016-01-01

    Grade 3 follicular lymphoma (FL) has aggressive clinical behavior. To evaluate the optimal first transplantation approach in relapsed/refractory grade 3 FL patients, we compared the long-term outcomes after allogeneic (allo-) vs autologous hematopoietic cell transplantation (auto-HCT) in the rituximab era. A total of 197 patients undergoing first reduced-intensity conditioning (RIC) allo-HCT or first auto-HCT during 2000-2012 were included. Rituximab-naive patients were excluded. Allo-HCT recipients were younger, more heavily pretreated and had a longer interval between diagnosis and HCT. The 5-year probabilities of non-relapse mortality (NRM), relapse/progression, PFS and overall survival (OS) for auto-HCT vs allo-HCT groups were 4% vs 27% (P<0.001), 61% vs 20% (P<0.001), 36% vs 51% (P=0.07) and 59% vs 54% (P=0.7), respectively. On multivariate analysis, auto-HCT was associated with reduced risk of NRM (relative risk (RR)=0.20; P=0.001). Within the first 11 months post HCT, auto- and allo-HCT had similar risks of relapse/progression and PFS. Beyond 11 months, auto-HCT was associated with higher risk of relapse/progression (RR=21.3; P=0.003) and inferior PFS (RR=3.2; P=0.005). In the first 24 months post HCT, auto-HCT was associated with improved OS (RR=0.42; P=0.005), but in long-time survivors (beyond 24 months) it was associated with inferior OS (RR=3.6; P=0.04). RIC allo-HCT as the first transplant approach can provide improved PFS and OS, in long-term survivors.

  1. A rare case of metastasized non-functional pancreatic neuroendocrine tumor with a good long-term survival

    PubMed Central

    Mirică, A; Bădărău, IA; Mirică, R; Păun, S; Păun, DL

    2016-01-01

    Background: Non-functional neuroendocrine tumors of the pancreas (NF-pNETs) are a varied group of extremely rare malignancies. The majority of patients already have liver metastases at the diagnosis moment, thus, treatment options are restricted, and the survival rate is reserved. Case report: We presented the case of 59-year-old patient, diagnosed with non-functional well-differentiated pancreatic neuroendocrine tumor grade II (NET G2) with the presence of chromogranin A, synaptophysin and somatostatin receptor 2, together with liver and bone metastases. Patient underwent a surgical excision of the pancreatic tumor, started long-acting somatostatin analogues (octreotide), interferon therapy for liver metastases and local radiotherapy for bone metastases. After one year, the patient developed diabetes, needing insulin therapy. At approximately three years after the diagnosis, the patient was still living, had a good quality of life, and was free of local recurrence of the tumor or other metastases. Conclusion: Our case report presented a rare case of metastatic non-functional well-differentiated pancreatic neuroendocrine tumor, involving a multidisciplinary therapeutic approach in order to obtain a good long-term survival. PMID:27928440

  2. Long-term survival of Bacillus spores in alcohol and identification of 90% ethanol as relatively more spori/bactericidal.

    PubMed

    Thomas, Pious

    2012-02-01

    This study was taken up with a view to generate basic information on spore hardiness to ethanol in various Bacillus species and related genera, and to assess the effectiveness of different levels of ethanol as a bacterial disinfectant. Predominantly spore-bearing cultures of five Bacillus spp. (B. pumilus, B. subtilis, B. megaterium, B. fusiformis and B. flexus) that were isolated from the spent-alcohol used during plant tissue culture work were challenged with aqueous ethanol (25, 50, 60, 70, 80 and 90% v/v) in 1 ml volumes at 10¹⁰⁻¹¹ CFU ml⁻¹. Monitoring the spore endurance through spotting and plating revealed prolonged tolerance (>12 months) at different alcohol levels depending on the organism except in 90% where no survival was observed beyond 2-12 months. Spores of related genera like Paenibacillus and Lysinibacillus also showed long-term ethanol survival. Alcohol tolerance of spore-forming organisms depended on the extent of spores and spore hardiness, which in turn varied with the organism, strain, age of culture, growing conditions and other factors as authenticated with ATCC strains of B. pumilus and B. subtilis. Aqueous 90% ethanol caused instant inactivation of vegetative cells in different spore formers and twelve other non-sporulating Gram-positive and Gram-negative organisms tested. Taking into account both vegetative cells and spores, the appropriate concentration of ethanol as a disinfectant emerged to be 90% followed by absolute ethanol compared with the generally recommended 70-80% level.

  3. G-CSF and Exenatide Might Be Associated with Increased Long-Term Survival of Allogeneic Pancreatic Islet Grafts

    PubMed Central

    Peixoto, Eduardo; Messinger, Shari; Mantero, Alejandro; Padilla-Téllez, Nathalia D.; Baidal, David A.; Alejandro, Rodolfo; Ricordi, Camillo; Inverardi, Luca

    2016-01-01

    Background Allogeneic human islet transplantation is an effective therapy for the treatment of patients with Type 1 Diabetes (T1D). The low number of islet transplants performed worldwide and the different transplantation protocols used limit the identification of the most effective therapeutic options to improve the efficacy of this approach. Methods We present a retrospective analysis on the data collected from 44 patients with T1D who underwent islet transplantation at our institute between 2000 and 2007. Several variables were included: recipient demographics and immunological characteristics, donor and transplant characteristics, induction protocols, and additional medical treatment received. Immunosuppression was induced with anti-CD25 (Daclizumab), alone or in association with anti-tumor necrosis factor alpha (TNF-α) treatments (Etanercept or Infliximab), or with anti-CD52 (Alemtuzumab) in association with anti-TNF-α treatments (Etanercept or Infliximab). Subsets of patients were treated with Filgrastim for moderate/severe neutropenia and/or Exenatide for post prandial hyperglycemia. Results The analysis performed indicates a negative association between graft survival (c-peptide level ≥ 0.3 ng/ml) and islet infusion volume, with the caveat that, the progressive reduction of infusion volumes over the years has been paralleled by improved immunosuppressive protocols. A positive association is instead suggested between graft survival and administration of Exenatide and Filgrastim, alone or in combination. Conclusion This retrospective analysis may be of assistance to further improve long-term outcomes of protocols for transplant of islets and other organs. PMID:27285580

  4. A rare case of metastasized non-functional pancreatic neuroendocrine tumor with a good long-term survival.

    PubMed

    A, Mirică; Ia, Bădărău; R, Mirică; S, Păun; Dl, Păun

    2016-01-01

    Background: Non-functional neuroendocrine tumors of the pancreas (NF-pNETs) are a varied group of extremely rare malignancies. The majority of patients already have liver metastases at the diagnosis moment, thus, treatment options are restricted, and the survival rate is reserved. Case report: We presented the case of 59-year-old patient, diagnosed with non-functional well-differentiated pancreatic neuroendocrine tumor grade II (NET G2) with the presence of chromogranin A, synaptophysin and somatostatin receptor 2, together with liver and bone metastases. Patient underwent a surgical excision of the pancreatic tumor, started long-acting somatostatin analogues (octreotide), interferon therapy for liver metastases and local radiotherapy for bone metastases. After one year, the patient developed diabetes, needing insulin therapy. At approximately three years after the diagnosis, the patient was still living, had a good quality of life, and was free of local recurrence of the tumor or other metastases. Conclusion: Our case report presented a rare case of metastatic non-functional well-differentiated pancreatic neuroendocrine tumor, involving a multidisciplinary therapeutic approach in order to obtain a good long-term survival.

  5. Suppression of T cells results in long-term survival of mouse heart xenografts in C6-deficient rats.

    PubMed

    Wu, G; Korsgren, O; van Rooijen, N; Tibell, A

    2001-11-01

    The present study aimed to investigate the role of cellular immune response in the absence of membrane attack complex (MAC) formation in the concordant mouse-to-rat heart xenografting. Hearts from BALB/c mice were transplanted into the neck vessels of C6-competent (C6(+)) and C6-deficient (C6(-)) PVG rats. Liposome-encapsulated dichloro-methylene diphosphonate (Lip-Cl2MDP) was administered at a dose of 10 ml/kg 2 days before transplantation and every 5 days thereafter. Cyclosporine (CsA) was administered intramuscularly (i.m.) at a dose of 15 mg/kg per day. The heart xenografts were harvested for immuno-histological analysis at the time of rejection and the functioning grafts were removed at 70 days after transplantation. In untreated C6(+) rats, xeno-grafts survived for 2.3 +/- 0.5 days. Treatment with CsA or Lip-Cl(2)MDP in C6(+) rats did not significantly affect graft survival (2.5 +/- 0.6 and 2.3 +/- 0.4 days, respectively). In untreated C6(-) rats, xenografts survived for 5.0 +/- 0.6 days. However, Lip-Cl(2)MDP in C6(-) rats resulted in a prolongation of graft survival to 11 +/- 2.3 days (P < 0.05 vs. untreated C6(-) rats), while treatment with CsA alone in these rats led to more than 70 days' survival in four out of six grafts (61 +/- 16 days). In untreated C6(+) rats, immunohistology showed a severe myocardial necrosis and thrombosis with a scarce cellular infiltrate in the rejected xenografts. By contrast, in untreated C6(-) rats, xenografts were heavily infiltrated by macrophages and T cells. The number of macrophages, but not T cells, was markedly reduced in Lip-Cl(2)MDP-treated rats. In CsA-treated C6(-) rats, the grafts harvested at 70 days after transplantation had a normal morphology, with a minimal cellular infiltrate. Our data indicate that MAC-mediated injury plays an essential role in concordant xenograft rejection. Once this mechanism has been prevented, suppression of T cells allows for long-term xenograft survival.

  6. Exposure to a glyphosate-based herbicide affects agrobiont predatory arthropod behaviour and long-term survival.

    PubMed

    Evans, Samuel C; Shaw, Emma M; Rypstra, Ann L

    2010-10-01

    Humans commonly apply chemicals to manage agroecosystems. If those chemicals influence the behaviour or survival of non-target arthropods, the food web could be altered in unintended ways. Glyphosate-based herbicides are among the most ubiquitous pesticides used around the world, yet little is known about if and how they might affect the success of terrestrial predatory arthropods in agroecosystems. In this study, we quantified the effects of a commercial formulation of a glyphosate-based herbicide on the activity of three predatory arthropod species that inhabit agricultural fields in the eastern United States. We also measured the survival of the most common species. We tested the reactions of the wolf spider, Pardosa milvina, to either direct application (topical) or contact with a treated substrate (residual). We quantified the reactions of a larger wolf spider, Hogna helluo, and a ground beetle, Scarites quadriceps, to a compound (topical plus residual) exposure. Pardosa milvina reduced locomotion time and distance under topical herbicide exposure, but increased speed and non-locomotory activity time on exposed substrate. Both H. helluo and S. quadriceps increased non-locomotory activity time under compound herbicide exposure. Over a period of 60 days post-exposure, residually exposed P. milvina exhibited lower survivorship compared to topically exposed and control groups. Thus, exposure of terrestrial arthropods to glyphosate-based herbicides affects their behaviour and long-term survival. These results suggest that herbicides can affect arthropod community dynamics separate from their impact on the plant community and may influence biological control in agroecosystems.

  7. Long-term survival of cardiac allografts induced by cyclophosphamide combined with CTLA4Ig-gene transfer mediated by adenoviral vector.

    PubMed

    Wang, G M; Ma, J B; Jin, Y Z; Feng, Y G; Hao, J; Gao, X; Xie, S S

    2006-11-01

    There is a need to achieve donor-specific tolerance in clinical organ transplantation, where potential benefits remain overshadowed by chronic rejection and the side-effects of long-term immunosuppressive therapy. It is known that the mature immune system in mice can be reprogrammed to accept a foreign graft as if it was "self". The AdCTLA4Ig-mediated gene transfer (SC) + cyclophosphamide (CP) treatment alone prolongs allograft survival but does not induce tolerance. However, in our study, the AdCTLA4Ig-mediated gene transfer combined with SC + CP treatment yielded significantly prolonged mean survival times (149.7 +/- 18.0 days), while those in the untreated or AdLacZ treated mice were rejected in normal fashion (5.3 +/- 0.5 and 5.2 +/- 0.4 days, respectively), and survival in the AdCTLA4Ig or SC + CP treated groups were 45.7 +/- 9.6 or 50.2 +/- 5.3 days, respectively. In conclusion, a protocol of AdCTLA4Ig + SC + CP improved the survival of DA-->LEW cardiac allografts.

  8. Long-term care use and socio-economic status in Belgium: a survival analysis using health care insurance data

    PubMed Central

    2013-01-01

    Background The small but growing literature on socio-economic inequality in morbidity among older persons suggests that social inequalities in health persist into old age. A largely separate body of literature looks at the predictors of long-term care use, in particular of institutional care. Various measures of socio-economic status are often included as control variables in these studies. Review articles generally conclude that the evidence for such variables being a predictor for institutionalization is “inconclusive”. In this paper we look at the association among older persons in Belgium between one particular measure of socio-economic status – preferential status in public health care insurance – and first use of home long-term care and residential care. Preferential status entitles persons to higher reimbursement rates for health care from the public health care insurance system and is conditional on low income. We also study whether preferential status is related to the onset of five important chronic conditions and the time of death. Methods We use survival analysis; the source of the data is a large administrative panel of a sample representative for all older persons in Belgium (1,268,740 quarterly observations for 69,562 individuals). Results We find a strong association between preferential status and the likelihood of home care use, but for residential care it is small for men and non-existent for women. We also find that preferential status is significantly related to the chance of getting two out five chronic conditions – COPD and diabetes, but not dementia, hip fracture and Parkinson’s disease – and to the probability of dying (not for women). For home care use and death, the association with preferential status declines with increasing age from age 65 onwards, such that it is near zero for those aged around 90 and older. Conclusion We find clear associations between an indicator of low income and home care use, some chronic

  9. Combining radiofrequency ablation and ethanol injection may achieve comparable long-term outcomes in larger hepatocellular carcinoma (3.1-4 cm) and in high-risk locations.

    PubMed

    Lin, Ji-Wei; Lin, Chen-Chun; Chen, Wei-Ting; Lin, Shi-Ming

    2014-08-01

    Radiofrequency ablation (RFA) is more effective for hepatocellular carcinoma (HCC) < 3 cm. Combining percutaneous ethanol injection and RFA for HCC can increase ablation; however, the long-term outcome remains unknown. The aim of this study was to compare long-term outcomes between patients with HCC of 2-3 cm versus 3.1-4 cm and in high-risk versus non-high-risk locations after combination therapy. The primary endpoint was overall survival and the secondary endpoint was local tumor progression (LTP). Fifty-four consecutive patients with 72 tumors were enrolled. Twenty-two (30.6%) tumors and 60 (83.3%) tumors were of 3.1-4 cm and in high-risk locations, respectively. Primary technique effectiveness was comparable between HCC of 2-3 cm versus 3.1-4 cm (98% vs. 95.5%, p = 0.521), and HCC in non-high risk and high-risk locations (100% vs. 96.7%, p = 1.000). The cumulative survival rates at 1 year, 3 years, and 5 years were 90.3%, 78.9%, and 60.3%, respectively, in patients with HCC of 2-3 cm; 95.0%, 84.4%, and 69.3% in HCC of 3.1-4.0 cm (p = 0.397); 90.0%, 71.1%, and 71.1% in patients with HCC in non-high-risk locations; and 92.7%, 81.6%, and 65.4% in high-risk locations (p = 0.979). The cumulative LTP rates at 1 year, 3 years, and 5 years were 10.2%, 32.6%, and 32.6%, respectively, in all HCCs; 12.6%, 33.9%, and 33.9% in HCC of 2-3 cm; 4.8%, 29.5%, and 29.5% in HCC of 3.1-4 cm (p = 0.616); 16.7%, 50.0%, and 50.0% in patients with HCC in non-high-risk locations; and 8.8%, 29.9%, and 29.9% in patients with HCC in high-risk locations (p = 0.283). The cumulative survival and LTP rates were not significantly different among the various subgroups. Combining RFA and percutaneous ethanol injection achieved comparable long-term outcomes in HCCs of 2-3 cm versus 3.1-4.0 cm and in high-risk versus non-high-risk locations. A randomized controlled or cohort studies with larger sample size are warranted.

  10. Long-term trends and survival analysis of esophageal and gastric cancer in Yangzhong, 1991-2013

    PubMed Central

    Xue, Hengchuan; Yao, Jun

    2017-01-01

    Objective To describe the long-term trends of the incidence, mortality and survival of upper digestive tract cancers in a high-risk area of China. Methods We extracted esophageal and gastric cancer cases diagnosed from 1991 to 2013 through the Yangzhong Cancer Registry and calculated the crude and age-standardized incidence and mortality rates. Cancer trends were calculated using the Joinpoint Regression Program and were reported using the annual percentage change (APC). The cancer-specific survival rates were evaluated and compared between groups using the Kaplan-Meier method and log-rank test. Results The age-standardized incidence rate of esophageal cancer declined from 107.06 per 100,000 person-years (male: 118.05 per 100,000 person-years; female: 97.42 per 100,000 person-years) in 1991 to 37.04 per 100,000 person-years (male: 46.43 per 100,000 person-years; female: 27.26 per 100,000 person-years) in 2013, with an APC of -2.5% (95% confidence interval (CI): -3.4%, -1.5%) for males and -4.9% (95% CI:-5.8%, -3.9%) for females. The age-standardized incidence rate of gastric cancer was 165.11 per 100,000 person-years (male: 225.39 per 100,000 person-years; female: 113.34 per 100,000 person-years) in 1991 and 53.46 per 100,000 person-years (male: 76.51 per 100,000 person-years; female: 32.43 per 100,000 person-years) in 2013, with the APC of -3.6% (95% CI: -4.5%, -2.7%) for males and -4.8% (95% CI: -5.7%, -3.9%) for females. The median survival time was 3.0 years for patients with esophageal or gastric cancer. Cancer cases detected after 2004 had a better prognosis. Conclusions The age-standardized incidence rates of both esophageal and gastric cancer continuously decreased since 1991 through 2013, whereas the mortality rate remained stable before 2004 and significantly declined following the massive endoscopic screening program initiated in 2004. The survival probability of patients with esophageal and gastric cancer has improved obviously in recent decades. PMID

  11. Investigation of long-term survival outcomes and failure patterns of patients with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: a retrospective analysis

    PubMed Central

    Zhao, Wei; Lei, Hao; Zhu, Xiaodong; Li, Ling; Qu, Song; Liang, Xia

    2016-01-01

    Intensity-modulated radiotherapy (IMRT) has replaced the conventional radiotherapy (2D-RT) and improved clinical efficacy in Nasopharyngeal Carcinoma (NPC) patients. In the present study, we retrospectively analyzed the clinical characteristics of patients with NPC treated with IMRT to assess the long-term survival outcomes and failure patterns. Of the 527 patients, One hundred and twenty-one patients experienced treatment failure, 86 patients developed distant metastases, and 12 patients developed a second primary tumor. The local and regional recurrence rates were 31.4% and 14.0%, respectively. The 5-year overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), regional relapse-free survival (RRFS), and distant metastatic relapse-free survival (DMFS) rates were 80.9%, 75.6%, 91.7%, 96.2%, and 83.0%, respectively. The 5-year LRFS rates of Stage T1-4 patients were 100.0%, 93.1%, 92.0%, and 85.8%, respectively. The 5-year DMFS rates of Stage N0-3 patients were 95.0%, 86.1%, 79.5%, and 67.2%, respectively. Multivariate analysis showed age and T-stage were independent predictors of OS, T-stage was an independent predictor of LRFS, and age and N-stage were independent predictors of PFS and DMFS. In summary, the improved treatment results with IMRT are primarily due to the achievement of a higher local tumor control rate and OS in NPC patients. However, distant metastasis was the most commonly observed failure pattern after treatment. These results provide deep insights about the value of IMRT in the treatment and prognosis of NPC patients. PMID:27894100

  12. The effects of long-term cadmium exposure on the growth and survival of juvenile bull trout (Salvelinus confluentus).

    PubMed

    Hansen, J A; Welsh, P G; Lipton, J; Suedkamp, M J

    2002-08-01

    Bull trout (Salvelinus confluentus) have been listed recently as threatened in the United States under the federal Endangered Species Act. This species currently resides, or historically resided, in several waterways that either are impacted or are under threat of impact from metals mining activities. We conducted a 55-day sub-chronic (i.e. sublethal) cadmium (Cd) exposure in water at 30 mg l(-1) (as CaCO(3)) hardness, pH 7.5, and 8 degrees C. Exposures were conducted using six replicate exposure tanks for each of the six treatments (five Cd concentrations and one control). Measured Cd concentrations were <0.013 (control), 0.052, 0.089, 0.197, 0.383, and 0.786 microg Cd l(-1). Exposure to 0.786 microg Cd l(-1) caused increased mortality (37%) and reduced growth (28% reduction in weight change) in fish exposed for 55 days. All Cd exposure concentrations caused significant whole body accumulation of Cd compared with controls. Our results indicate that even though fish are significantly accumulating Cd in each non-control treatment, growth reductions in bull trout occurred only at Cd concentrations that also caused significant mortality. The Cd concentration that reduced growth and survival in this long-term exposure (0.786 microg Cd l(-1)) is greater than the recently-revised US federal aquatic life criteria (ALC) value for the corresponding hardness concentration (ALC=0.62 microg Cd l(-1) for acute effects and 0.11 microg Cd l(-1) for chronic effects).

  13. Long-term survival of patients with CLL after allogeneic transplantation: a report from the European Society for Blood and Marrow Transplantation.

    PubMed

    van Gelder, M; de Wreede, L C; Bornhäuser, M; Niederwieser, D; Karas, M; Anderson, N S; Gramatzki, M; Dreger, P; Michallet, M; Petersen, E; Bunjes, D; Potter, M; Beelen, D; Cornelissen, J J; Yakoub-Agha, I; Russell, N H; Finke, J; Schoemans, H; Vitek, A; Urbano-Ispízua, Á; Blaise, D; Volin, L; Chevallier, P; Caballero, D; Putter, H; van Biezen, A; Henseler, A; Schönland, S; Kröger, N; Schetelig, J

    2017-03-01

    Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients.

  14. Long-Term Survival of Dental Implants Placed in the Grafted Maxillary Sinus: Systematic Review and Meta-Analysis of Treatment Modalities

    PubMed Central

    Duttenhoefer, Fabian; Souren, Cyriel; Menne, Dieter; Emmerich, Dominik; Schön, Ralf; Sauerbier, Sebastian

    2013-01-01

    Background A prevalent modality to increase the amount of available bone prior to implantation is grafting of the maxillary sinus. Multiple factors such as the surgical technique, moment of implant placement as well as grafting materials and membranes are known to affect implant survival. However, the role of different factor combinations and associated reciprocal effects remain unclear. Conventional statistical methods do not consider inconsistency of study designs and do not take covariables into account. Hence, a systematic research and meta-analysis was conducted to investigate the influence of various treatment modalities on implant survival in the grafted maxillary sinus. Materials and Methods A meta-analysis was conducted according to the PRISMA guidelines. Articles published from 1980 through January 2013 were electronically and manually searched in MEDLINE (Ovid), the Cochrane Register of Controlled Trials, the Database of Abstracts of Effects, and the Cochrane Database of Systematic Reviews. Clinical reports on single intervention sinus augmentation with root-form implants, a minimum of 10 patients and 6 months of loading were eligible for inclusion if implant survival was stated or calculable. Results were calculated by non-parametric univariate Kaplan-Meier analysis and Bayesian multivariate interval-censored Cox regression. Results A total of 122 publications on 16268 endosseous implants placed in grafted maxillary sinus were included. The treatment parameters surgical approach, grafting material and implant type showed no selective preference. However, application of membranes showed a significantly reduced hazard-ratio, independent of other co-factors. Conclusions The use of membranes is the most significant factor to achieve long-term implant survival in sinus augmentation procedures. More data exceeding 3 years follow-up are needed to address prospective confounding and improve clinical evidence. PMID:24058679

  15. Long-term Survival after Lapatinib Rechallenge in Isolated Brain Metastasis of HER2-positive Breast Cancer

    PubMed Central

    Karagöz, Bülent; Özgün, Alpaslan; Emirzeoğlu, Levent; Tunçel, Tolga; Çelik, Serkan; Bilgi, Oğuz; Kara, Kemal

    2015-01-01

    Lapatinib is an effective drug in HER2-positive breast cancer. We present a case with successful treatment of lapatinib in brain metastasis of HER2+ breast cancer. Forty-eight years old woman was admitted our clinic with early breast cancer. In third years after adjuvant chemotherapy and trastuzumab, isolated and multiple brain metastasis were detected. After whole brain RT, lapatinib (with capecitabine for 10 months and with letrozole for 3 months) has been used. Volumetric reduction of lesions was achieved and symptoms disappeared. When lapatinib discontinued, brain metastasis relapses. Lapatinib plus capecitabine reinduction has been started. Totally, longer survival than 45 months was achieved after first brain metastasis detection. Because both combinations of lapatinib with capecitabine and letrozole were effective and reinduction treatment was successful, presented case has strongly supported activity of lapatinib treatment in brain metastasis of HER2+ breast cancer.

  16. Rho-Signaling-Directed YAP/TAZ Activity Underlies the Long-Term Survival and Expansion of Human Embryonic Stem Cells.

    PubMed

    Ohgushi, Masatoshi; Minaguchi, Maki; Sasai, Yoshiki

    2015-10-01

    Human embryonic stem cells (hESCs) can survive and proliferate for an extended period of time in culture, but unlike that of tumor-derived cells, this form of cellular immortality does not depend on genomic aberrations. In this study, we sought to elucidate the molecular basis of this long-term growth property of hESCs. We found that the survival of hESCs depends on the small GTPase Rho and its activator AKAP-Lbc. We show that AKAP-Lbc/Rho signaling sustains the nuclear function of the transcriptional cofactors YAP and TAZ by modulating actin microfilament organization. By inducing reprogramming and differentiation, we found that dependency on this Rho signaling pathway is associated with the pluripotent state. Thus, our findings show that the capacity of hESCs to undergo long-term expansion in vitro is intrinsically coupled to their cellular identity through interconnected molecular circuits that link cell survival to pluripotency.

  17. Analysis of in hospital mortality and long-term survival excluding in hospital mortality after open surgical repair of ruptured abdominal aortic aneurysm

    PubMed Central

    Gwon, Jun Gyo; Cho, Yong-Pil; Han, Young Jin; Noh, Min Su

    2016-01-01

    Purpose The aim of this study was to confirm the factors that affect the mortality associated with the open surgical repair of ruptured abdominal aortic aneurysm (rAAA) and to analyze the long-term survival rates. Methods A retrospective review was performed on a prospectively collected database that included 455 consecutive patients who underwent open surgical repair for AAA between January 2001 and December 2012. We divided our analysis into in-hospital and postdischarge periods and analyzed the risk factors that affected the long-term survival of rAAA patients. Results Of the 455 patients who were initially screened, 103 were rAAA patients, and 352 were non-rAAA (nAAA) patients. In the rAAA group, 25 patients (24.2%) died in the hospital and 78 were discharged. Long-term survival was significantly better in the nAAA group (P = 0.001). The 2-, 5-, and 10-year survival rates of the rAAA patients were 87%, 73.4%, and 54.1%, respectively. Age (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.02–.08; P < 0.001) and aneurysm rupture (HR, 1.96; 95% CI, 1.12–.44; P = 0.01) significantly affected long-term survival. Conclusion Preoperative circulatory failure is the most common cause of death for in-hospital mortality of rAAA patients. After excluding patients who have died during the perioperative period, age is the only factor that affects the survival of rAAA patients. PMID:27904852

  18. A Broad Range of Dose Optima Achieve High-level, Long-term Gene Expression After Hydrodynamic Delivery of Sleeping Beauty Transposons Using Hyperactive SB100x Transposase

    PubMed Central

    Podetz-Pedersen, Kelly M; Olson, Erik R; Somia, Nikunj V; Russell, Stephen J; McIvor, R Scott

    2016-01-01

    The Sleeping Beauty (SB) transposon system has been shown to enable long-term gene expression by integrating new sequences into host cell chromosomes. We found that the recently reported SB100x hyperactive transposase conferred a surprisingly high level of long-term expression after hydrodynamic delivery of luciferase-encoding reporter transposons in the mouse. We conducted dose-ranging studies to determine the effect of varying the amount of SB100x transposase-encoding plasmid (pCMV-SB100x) at a set dose of luciferase transposon and of varying the amount of transposon-encoding DNA at a set dose of pCMV-SB100x in hydrodynamically injected mice. Animals were immunosuppressed using cyclophosphamide in order to prevent an antiluciferase immune response. At a set dose of transposon DNA (25 µg), we observed a broad range of pCMV-SB100x doses (0.1–2.5 µg) conferring optimal levels of long-term expression (>1011 photons/second/cm2). At a fixed dose of 0.5 μg of pCMV-SB100x, maximal long-term luciferase expression (>1010 photons/second/cm2) was achieved at a transposon dose of 5–125 μg. We also found that in the linear range of transposon doses (100 ng), co-delivering the CMV-SB100x sequence on the same plasmid was less effective in achieving long-term expression than delivery on separate plasmids. These results show marked flexibility in the doses of SB transposon plus pCMV-SB100x that achieve maximal SB-mediated gene transfer efficiency and long-term gene expression after hydrodynamic DNA delivery to mouse liver. PMID:26784638

  19. Long-term event-free and overall survival after risk-adapted melphalan and SCT for systemic light chain amyloidosis

    PubMed Central

    Landau, H; Smith, M; Landry, C; Chou, J F; Devlin, S M; Hassoun, H; Bello, C; Giralt, S; Comenzo, R L

    2017-01-01

    Stem cell transplantation (SCT), an effective therapy for amyloid light chain (AL) amyloidosis patients, is associated with low treatment-related mortality (TRM) with appropriate patient selection and risk-adapted dosing of melphalan (RA-SCT). Consolidation after SCT increases hematologic complete response (CR) rates and may improve overall survival (OS) for patients with survival (EFS) with RA-SCT was 4.04 years (95% confidence interval (CI): 3.41–5.01 years); median OS was 10.4 years (95% CI: 7.3–not achieved). Patients with CR at 12 months after SCT had significantly longer EFS (P=0.01) and OS (P=0.04). In a multivariate analysis, melphalan dose had no impact on EFS (P=0.26) or OS (P=0.11). For selected patients, RA-SCT was safe and was associated with extended long-term survival. With the availability of novel agents for consolidation, RA-SCT remains a very effective and important backbone treatment for AL amyloidosis. PMID:27560108

  20. Attention Problems, Phonological Short-Term Memory, and Visuospatial Short-Term Memory: Differential Effects on Near- and Long-Term Scholastic Achievement

    ERIC Educational Resources Information Center

    Sarver, Dustin E.; Rapport, Mark D.; Kofler, Michael J.; Scanlan, Sean W.; Raiker, Joseph S.; Altro, Thomas A.; Bolden, Jennifer

    2012-01-01

    The current study examined individual differences in children's phonological and visuospatial short-term memory as potential mediators of the relationship among attention problems and near- and long-term scholastic achievement. Nested structural equation models revealed that teacher-reported attention problems were associated negatively with…

  1. Developing Long-Term Computing Skills among Low-Achieving Students via Web-Enabled Problem-Based Learning and Self-Regulated Learning

    ERIC Educational Resources Information Center

    Tsai, Chia-Wen; Lee, Tsang-Hsiung; Shen, Pei-Di

    2013-01-01

    Many private vocational schools in Taiwan have taken to enrolling students with lower levels of academic achievement. The authors re-designed a course and conducted a series of quasi-experiments to develop students' long-term computing skills, and examined the longitudinal effects of web-enabled, problem-based learning (PBL) and self-regulated…

  2. Pre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors

    PubMed Central

    Servais, Sophie; Porcher, Raphaël; Xhaard, Alienor; Robin, Marie; Masson, Emeline; Larghero, Jerome; Ribaud, Patricia; Dhedin, Nathalie; Abbes, Sarah; Sicre, Flore; Socié, Gérard; de Latour, Regis Peffault

    2014-01-01

    Mobilized peripheral blood has become the predominant stem cell source for allogeneic hematopoietic cell transplantation. In this retrospective single center study of 442 patients with hematologic malignancies, we analyzed prognostic factors for long-term survival after peripheral blood stem cell transplantation from HLA-matched related or unrelated donors. To account for disease/status heterogeneity, patients were risk-stratified according to the Disease Risk Index. Five-year overall survival was similar after transplants with matched related and unrelated donors (45% and 46%, respectively; P=0.49). Because donor age ≥60 years impacted outcome during model building, we further considered 3 groups of donors: matched unrelated (aged <60 years by definition), matched related aged <60 years and matched related aged ≥60 years. In multivariate analysis, the donor type/age group and the graft CD34+ and CD3+ cell doses impacted long-term survival. Compared with matched unrelated donor transplant, transplant from matched related donor <60 years resulted in similar long-term survival (P=0.67) while transplant from matched related donor ≥60 years was associated with higher risks for late mortality (hazard ratio (HR) 4.41; P=0.006) and treatment failure (HR: 6.33; P=0.009). Lower mortality risks were observed after transplant with CD34+ cell dose more than 4.5×106/kg (HR: 0.56; P=0.002) and CD3+ cell dose more than 3×108/kg (HR: 0.61; P=0.01). The Disease Risk Index failed to predict survival. We built an “adapted Disease Risk Index” by modifying risks for myeloproliferative neoplasms and multiple myeloma that improved stratification ability for progression-free survival (P=0.04) but not for overall survival (P=0.82). PMID:24241489

  3. Pre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors.

    PubMed

    Servais, Sophie; Porcher, Raphaël; Xhaard, Alienor; Robin, Marie; Masson, Emeline; Larghero, Jerome; Ribaud, Patricia; Dhedin, Nathalie; Abbes, Sarah; Sicre, Flore; Socié, Gérard; Peffault de Latour, Regis

    2014-03-01

    Mobilized peripheral blood has become the predominant stem cell source for allogeneic hematopoietic cell transplantation. In this retrospective single center study of 442 patients with hematologic malignancies, we analyzed prognostic factors for long-term survival after peripheral blood stem cell transplantation from HLA-matched related or unrelated donors. To account for disease/status heterogeneity, patients were risk-stratified according to the Disease Risk Index. Five-year overall survival was similar after transplants with matched related and unrelated donors (45% and 46%, respectively; P=0.49). Because donor age ≥60 years impacted outcome during model building, we further considered 3 groups of donors: matched unrelated (aged <60 years by definition), matched related aged <60 years and matched related aged ≥60 years. In multivariate analysis, the donor type/age group and the graft CD34(+) and CD3(+) cell doses impacted long-term survival. Compared with matched unrelated donor transplant, transplant from matched related donor <60 years resulted in similar long-term survival (P=0.67) while transplant from matched related donor ≥60 years was associated with higher risks for late mortality (hazard ratio (HR) 4.41; P=0.006) and treatment failure (HR: 6.33; P=0.009). Lower mortality risks were observed after transplant with CD34(+) cell dose more than 4.5×10(6)/kg (HR: 0.56; P=0.002) and CD3(+) cell dose more than 3×10(8)/kg (HR: 0.61; P=0.01). The Disease Risk Index failed to predict survival. We built an "adapted Disease Risk Index" by modifying risks for myeloproliferative neoplasms and multiple myeloma that improved stratification ability for progression-free survival (P=0.04) but not for overall survival (P=0.82).

  4. Temporal profile of inflammatory response to fracture and hemorrhagic shock: Proposal of a novel long-term survival murine multiple trauma model.

    PubMed

    Kleber, Christian; Becker, Christopher A; Malysch, Tom; Reinhold, Jens M; Tsitsilonis, Serafeim; Duda, Georg N; Schmidt-Bleek, Katharina; Schaser, Klaus D

    2015-07-01

    Hemorrhagic shock (hS) interacts with the posttraumatic immune response and fracture healing in multiple trauma. Due to the lack of a long-term survival multiple trauma animal models, no standardized analysis of fracture healing referring the impact of multiple trauma on fracture healing was performed. We propose a new long-term survival (21 days) murine multiple trauma model combining hS (microsurgical cannulation of carotid artery, withdrawl of blood and continuously blood pressure measurement), femoral (osteotomy/external fixation) and tibial fracture (3-point bending technique/antegrade nail). The posttraumatic immune response was measured via IL-6, sIL-6R ELISA. The hS was investigated via macrohemodynamics, blood gas analysis, wet-dry lung ration and histologic analysis of the shock organs. We proposed a new murine long-term survival (21 days) multiple trauma model mimicking clinical relevant injury patterns and previously published human posttraumatic immune response. Based on blood gas analysis and histologic analysis of shock organs we characterized and standardized our murine multiple trauma model. Furthermore, we revealed hemorrhagic shock as a causative factor that triggers sIL-6R formation underscoring the fundamental pathophysiologic role of the transsignaling mechanism in multiple trauma.

  5. Effectiveness of venlafaxine, extended release formulation, in the short-term and long-term treatment of generalized anxiety disorder: results of a survival analysis.

    PubMed

    Montgomery, Stuart A; Mahé, Vincent; Haudiquet, Vincent; Hackett, David

    2002-12-01

    A survival analysis of data from two placebo-controlled, randomized, long-term (6-month) studies was used to examine the effectiveness of venlafaxine, extended release (XR) formulation, in patients with generalized anxiety disorder (GAD). Patients in a placebo-controlled, flexible-dose study received 75 to 225 mg/day venlafaxine XR, while patients in a placebo-controlled, fixed-dose study received once-daily venlafaxine XR doses of 37.5 mg, 75 mg, or 150 mg. The survival analysis was based on the clinician's decision to discontinue treatment in a placebo-controlled study and incorporated data from all patients who were randomized. In each study, placebo-treated patients discontinued treatment due to lack of efficacy more frequently and earlier than those receiving venlafaxine XR (p < 0.001, log-rank test). A dose-response relationship was apparent, with the lowest rate of withdrawal seen at the highest venlafaxine XR dose. Survival curves for discontinuations due to adverse events did not differ significantly in either study. These results were consistent with the conventional intent-to-treat efficacy assessments of changes in anxiety severity, highlighting the superiority of venlafaxine XR over placebo in the long-term treatment of GAD. Overall, these results demonstrate the clinical effectiveness of venlafaxine XR in the short-term and long-term treatment of GAD.

  6. Long-term costs of inflated self-estimate on academic performance among adolescent students: a case of second-language achievements.

    PubMed

    Yang, Mu-Li; Chuang, Hsueh-Hua; Chiou, Wen-Bin

    2009-12-01

    Past studies suggest that the adaptive or maladaptive consequences of inflated self-estimate, one form of positive illusions, require further investigation. 308 freshmen at a junior college (164 women, 144 men; M age = 19.8 yr., SD = 1.1) participated in a longitudinal study during a 2-yr. period. There were three assessments of short- and long-term effects of overly positive self-estimates on second-language achievement. Students' overestimation of subsequent performance appears to be associated with lower achievement. Those students with apparently inflated self-estimates performed marginally better on the first assessment but worse in the second and final assessments. Students with more accurate self-estimates showed improvement on all assessments. The findings suggested that overinflated self-estimates, i.e., positive illusions, among adolescent students might lead to a lower achievement over the long-term.

  7. Perioperative outcomes and long-term survival in clinically early-stage thymic malignancies: video-assisted thoracoscopic thymectomy versus open approaches

    PubMed Central

    Wang, Hao; Gu, Zhitao; Tan, Lijie; Fu, Jianhua; Shen, Yi; Wei, Yucheng; Zhang, Peng; Han, Yongtao; Chen, Chun; Zhang, Renquan; Li, Yin; Chen, Keneng; Chen, Hezhong; Liu, Yongyu; Cui, Youbing; Wang, Yun; Pang, Liewen; Yu, Zhentao; Zhou, Xinming; Liu, Yangchun; Liu, Yuan

    2016-01-01

    Background Video-assisted thoracoscopic surgery (VATS) theoretically offers advantages over open thymectomy for clinically early-stage (Masaoka-Koga stage I and II) thymic malignancies. However, long-term outcomes have not been well studied. We compared the postoperative outcomes and survival from a cohort study based on the database of the Chinese Alliance for Research in Thymomas (ChART). Methods Between 1994 and 2012, data of 1,117 patients having surgery for clinically early-stage (Masaoka-Koga stage I and II) tumors were enrolled for the study. Among them, 241 cases underwent VATS thymectomy (VATS group), while 876 cases underwent open thymectomy (Open group). Univariate analyses were used to compare the clinical character and perioperative outcomes between the two groups. And multivariate analysis was performed to determine the independent predictive factors for long-term survival. Results Compared with the Open group, the VATS group had higher percentage of total thymectomy (80.5% vs. 73.9%, P=0.028), resection rate (98.8% vs. 88.7%, P=0.000) and less recurrence (2.9% vs. 16.0%, P=0.000). Five-year overall survival was 92% after VATS and 92% after open thymectomy, with no significant difference between the two groups (P=0.15). However, 5-year disease free survival were 92% in VATS group and 83% in Open group (P=0.011). Cox proportional hazards model revealed that WHO classification, Masaoka-Koga stage and adjuvant therapy were independent predictive factors for overall survival, while surgical approach had no significant impact on long-term outcome. Conclusions This study suggests that VATS thymectomy is an effective approach for clinically early-stage thymic malignancies. And it may offer better perioperative outcomes, as well as equal oncological survival. PMID:27114834

  8. Long-term survival and serial assessment of stroke damage and recovery – practical and methodological considerations

    PubMed Central

    Modo, Michel

    2012-01-01

    Impairments caused by stroke remain the main cause for adult disability. Despite a vigorous research effort, only 1 thrombolytic treatment has been approved in acute stroke (<3h). The limitations of preclinical studies and how these can be overcome have been the subject of various guidelines. However, often these guidelines focus on the acute stroke setting and omit long-term outcome measures, such as behaviour and neuroimaging. The considerations and practicalities of including the serial assessment of these approaches and their significance to establish therapeutic efficacy are discussed here. PMID:22389748

  9. Impact of donor-recipient sex match on long-term survival after heart transplantation in children: An analysis of 5797 pediatric heart transplants.

    PubMed

    Kemna, Mariska; Albers, Erin; Bradford, Miranda C; Law, Sabrina; Permut, Lester; McMullan, D Mike; Law, Yuk

    2016-03-01

    The effect of donor-recipient sex matching on long-term survival in pediatric heart transplantation is not well known. Adult data have shown worse survival when male recipients receive a sex-mismatched heart, with conflicting results in female recipients. We analyzed 5795 heart transplant recipients ≤ 18 yr in the Scientific Registry of Transplant Recipients (1990-2012). Recipients were stratified based on donor and recipient sex, creating four groups: MM (N = 1888), FM (N = 1384), FF (N = 1082), and MF (N = 1441). Males receiving sex-matched donor hearts had increased unadjusted allograft survival at five yr (73.2 vs. 71%, p = 0.01). However, this survival advantage disappeared with longer follow-up and when adjusted for additional risk factors by multivariable Cox regression analysis. In contrast, for females, receiving a sex-mismatched heart was associated with an 18% higher risk of allograft loss over time compared to receiving a sex-matched heart (HR 1.18, 95% CI: 1.00-1.38) and a 26% higher risk compared to sex-matched male recipients (HR 1.26, 95% CI: 1.10-1.45). Females who receive a heart from a male donor appear to have a distinct long-term survival disadvantage compared to all other groups.

  10. Long-term survival with a stentless free-hand Batista pericardial aortic valve prosthesis: A case report

    PubMed Central

    Becerra, Valentina; Labbé, Javier; Cataldo, Anthony; Becerra, Eduardo

    2014-01-01

    INTRODUCTION Stented bovine pericardial prosthetic valves are a good option for older patients, except when there is a fragile small aortic annulus, when, if there is no contraindication to anticoagulation, a mechanical prosthesis may be indicated. PRESENTATION OF CASE We report a 72 year-old man who underwent coronary bypass grafting and aortic valve replacement with a stentless valve fashioned from bovine pericardium using the Batista technique. Despite early sternal infection and dehiscence, and renal and respiratory failure during 15 years follow-up, he remains alive and self-sufficient. Echocardiography demonstrates a well-functioning aortic valve. DISCUSSION When Batista reported his first 60 patients, concerns were raised about the surgical feasibility of constructing the valve and its long-term durability. Our case perhaps addresses both concerns. CONCLUSION Replacement of the aortic valve with a free-hand Batista pericardial valve is a feasible option in a suitable and carefully selected patient. PMID:25524300

  11. Long-term outcome of infective endocarditis: A study on patients surviving over one year after the initial episode treated in a Finnish teaching hospital during 25 years

    PubMed Central

    Heiro, Maija; Helenius, Hans; Hurme, Saija; Savunen, Timo; Metsärinne, Kaj; Engblom, Erik; Nikoskelainen, Jukka; Kotilainen, Pirkko

    2008-01-01

    Background Only a few previous studies have focused on the long-term prognosis of the patients with infective endocarditis (IE). Our purpose was to delineate factors potentially associated with the long-term outcome of IE, recurrences of IE and requirement for late valve surgery. Methods A total of 326 episodes of IE in 303 patients were treated during 1980–2004 in the Turku University Hospital. We evaluated the long-term outcome and requirement for late valve surgery for 243 of these episodes in 226 patients who survived longer than 1 year after the initial admission. Factors associated with recurrences were analysed both for the 1-year survivors and for all 303 patients. Results The mean (SD) follow-up time for the 1-year survivors was 11.5 (7.3) years (range 25 days to 25.5 years). The overall survival was 95%, 82%, 66%, 51% and 45% at 2, 5, 10, 15 and 20 years. In age and sex adjusted multivariate analyses, significant predictors for long-term overall mortality were heart failure within 3 months of admission (HR 1.97, 95% CI 1.27 to 3.06; p = 0.003) and collagen disease (HR 2.54, 95% CI 1.25 to 5.19; p = 0.010) or alcohol abuse (HR 2.39, 95% CI 1.30 to 4.40; p = 0.005) as underlying conditions, while early surgery was significantly associated with lower overall mortality rates (HR 0.31, 95% CI 0.17 to 0.58; p < 0.001). Heart failure was also significantly associated with the long-term cardiac mortality (p = 0.032). Of all 303 patients, 20 had more than 1 disease episode. Chronic dialysis (p = 0.002), intravenous drug use (p = 0.002) and diabetes (p = 0.015) were significant risk factors for recurrent episodes of IE, but when analysed separately for the 1-year survivors, only chronic dialysis remained significant (p = 0.017). Recurrences and late valve surgery did not confer a poor prognosis. Conclusion Heart failure during the index episode of IE was the complication, which significantly predicted a poor long-term outcome. Patients who underwent surgery

  12. Adoptive transfer of DNT cells induces long-term cardiac allograft survival and augments recipient CD4(+)Foxp3(+) Treg cell accumulation.

    PubMed

    Zhang, Zhu-Xu; Lian, Dameng; Huang, Xuyan; Wang, Shuang; Sun, Hongtao; Liu, Weihua; Garcia, Bertha; Min, Wei-Ping; Jevnikar, Anthony M

    2011-01-15

    Regulatory T (Treg) cells play an important role in the regulation of immune responses but whether Treg will induce tolerance in transplant recipients in the clinic remains unknown. Our previous studies have shown that TCRαβ(+)CD3(+)CD4⁻CD8⁻NK1.1⁻ (double negative, DN) T cells suppress T cell responses and prolong allograft survival in a single locus MHC-mismatched mouse model. In this study, we investigated the role of DNT cells in a more robust, fully MHC-mismatched BALB/c to C57BL/6 transplantation model, which may be more clinically relevant. Adoptive transfer of DNT cells in combination with short-term rapamycin treatment (days 1-9) induced long-term heart allograft survival (101±31 vs. 39±13 days rapamycin alone, p<0.01). Furthermore adoptive transfer DNT cells augmented CD4+Foxp3+ Treg cells accumulation in transplant recipients while depletion of CD4(+) Treg cells by anti-CD25 inhibited the effect of DNT cells on long-term graft survival (48±12 days vs. 101±31 days, p<0.001). In conclusion, DNT cells combined with short-term immunosuppression can prolong allograft survival, which may be through the accumulation of CD4(+)Foxp3(+) Treg cells in the recipient. Our result suggests that allograft tolerance may require the co-existence of different type Treg cell phenotypes which are affected by current immunosuppression.

  13. Age-specific survival and philopatry in three species of European ducks: a long-term study

    USGS Publications Warehouse

    Blums, P.; Mednis, A.; Bauga, I.; Nichols, J.D.; Hines, J.E.

    1996-01-01

    Capture-recapture and band recovery models were used to estimate age-specific survival probabilities for female Northern Shovelers (Anas clypeata), Common Pochards (Aythya ferina), and Tufted Ducks (Aythya.fuligula) at Engure Marsh, Latvia, in 1964-1993. We banded more than 65,100 day-old ducklings of both sexes and captured 10,211 incubating females (3,713 new bandings and 6,498 recaptures). We developed a set of 3-age capture-recapture models to estimate annual survival rates for female ducklings, yearlings (SY), and adults (ASY) using programs SURGE and SURVIV and selected parsimonious models using a method developed bv Akaike (1973). Survival rates of SY and ASY females were highest-for Tufted Ducks intermediate for Common Pochards, and lowest for Northern Shovelers. Survival rates of SY and ASY females varied in parallel for shovelers and pochards. We believe that much of the difference in survival estimates between SY and ASY birds was caused by mortality rather than permanent emigration. Estimates of day-old duckling survival, reflecting both mortality and permanent emigration, were 0.12 for shoveler, 0.06 for pochard, and 0.03 for Tufted Duck. For all species, duckling survival varied over years, but the pattern of variation was not similar to that of the other age classes. Estimates of survival using band recovery data for SY + ASY female pochards and Tufted Ducks were similar to the capture-recapturee stimates, suggestingt hat surviving females returned to the breeding marsh with probabilities approaching 1.

  14. Recent trends in long-term survival of patients with chronic myelocytic leukemia: disclosing the impact of advances in therapy on the population level.

    PubMed

    Brenner, Hermann; Gondos, Adam; Pulte, Dianne

    2008-10-01

    Within the past decades, major advances in therapy for chronic myelocytic leukemia, including allogeneic hematopoietic stem cell transplantation, interferon therapy, and, more recently, also therapy with the tyrosine kinase inhibitor imatinib, have entered clinical practice. The impact of these advances on long-term survival on the population level should be disclosed as timely as possible. We estimated trends in age specific 5- and 10-year relative survival of chronic myelocytic leukemia patients in the United States from 1990-1992 to 2002-2004. Our analysis is based on records from 8,329 patients aged 15 years or older with a first diagnosis of chronic myelocytic leukemia included in the 1973-2004 data base of the Surveillance, Epidemiology, and End Results Program. Period analysis was used to disclose recent developments with minimum delay. Overall, 5-year relative survival increased from 27 to 49%, and 10-year relative survival increased from 9.5 to 34% between 1990-92 and 2002-04. The increase was most dramatic for younger patients, with 10-year relative survival increasing from 16 to 72% in age group 15-44 years, from 12 to 54% in age group 45-54 years, and from 8 to 34% in age group 55-64 years (p<0.0001 in all cases). Improvements were more modest and not statistically significant, and survival remained at much lower levels among age groups 65-74 and 75+ years. Our analysis discloses a dramatic recent increase in long-term survival of younger patients with chronic myelocytic leukemia which most likely reflects rapid dissemination of advances in therapy on the population level.

  15. Heart rate variability during hemodialysis is an indicator for long-term vascular access survival in uremic patients

    PubMed Central

    Huang, Ya-Ting; Chang, Yu-Ming; Chen, I-Ling; Yang, Chuan-Lan; Leu, Show-Chin; Su, Hung-Li; Kao, Jsun-Liang; Tsai, Shih-Ching; Jhen, Rong-Na; Tang, Woung-Ru

    2017-01-01

    Background Vascular access (VA) is the lifeline of hemodialysis patients. Although the autonomic nervous system might be associated with VA failure (VAF), it has never been addressed in previous studies. This study aimed to evaluate the predictive values of the heart rate variability (HRV) indices for long-term VA outcomes. Methods This retrospective study was conducted using a prospectively established cohort enrolling 175 adult chronic hemodialysis patients (100 women, mean age 65.1 ± 12.9 years) from June 2010 to August 2010. Each participant received a series of HRV measurements at enrollment. After a 60-month follow-up period, we retrospectively reviewed all events and therapeutic procedures of the VAs which existed at the enrollment and during the follow-up period. Results During the 60-month follow-up period, 37 (26.8%) had VAF but 138 (73.2%) didn’t. The values of most HRV indices were statistically increased during hemodialysis since initiation in the non-VAF group, but not in the VAF group. Among all participants, the independent indicators for VAF included higher normalized high-frequency (nHF) activity [hazard ratio (HR) 1.04, p = 0.005], lower low-frequency/high-frequency (LF/HF) ratio (HR 0.80, p = 0.015), experience of urokinase therapy (HR 11.18, p = 0.002), percutaneous transluminal angioplasty (HR 2.88, p = 0.003) and surgical thrombectomy (HR 2.36, p = 0.035), as well as higher baseline serum creatinine (HR 1.07, p = 0.027) and potassium level (HR 1.58, p = 0.037). In subgroup analysis, a lower sympathetic activity indicated by lower LF/HF ratio was an independent indicator for VAF (HR 0.61, p = 0.03) for tunneled cuffed catheter, but conversely played a protective role against VAF (HR 1.27, p = 0.002) for arteriovenous fistula. Conclusions HRV is a useful tool for predicting long-term VAF among hemodialysis patients. PMID:28249028

  16. Density-Dependent Recycling Promotes the Long-Term Survival of Bacterial Populations during Periods of Starvation

    PubMed Central

    Takano, Sotaro; Pawlowska, Bogna J.; Gudelj, Ivana

    2017-01-01

    ABSTRACT The amount of natural resources in the Earth’s environment is in flux, which can trigger catastrophic collapses of ecosystems. How populations survive under nutrient-poor conditions is a central question in ecology. Curiously, some bacteria persist for a long time in nutrient-poor environments. Although this survival may be accomplished through cell death and the recycling of dead cells, the importance of these processes and the mechanisms underlying the survival of the populations have not been quantitated. Here, we use microbial laboratory experiments and mathematical models to demonstrate that death and recycling are essential activities for the maintenance of cell survival. We also show that the behavior of the survivors is governed by population density feedback, wherein growth is limited not only by the available resources but also by the population density. The numerical simulations suggest that population density-dependent recycling could be an advantageous behavior under starvation conditions. PMID:28174316

  17. Survival outcome of radioiodine therapy in post thyroidectomy thyroid carcinoma patients: Outcome of long term follow up

    NASA Astrophysics Data System (ADS)

    Haque, F.; Nahar, N.; Sultana, S.; Nasreen, F.; Jabin, Z.; Alam, A. S. M. M.

    2016-03-01

    The overall prognosis of patients with thyroid carcinoma is excellent whenever managed following best practice guidelines. Objective: To calculate sex and age group affected by thyroid cancer; to compare between single or multiple dose of radio ablation needed after thyroidectomy and to determine the percentage of patients become disease free during their follow up. Methods: This was a retrospective study done in NINMAS, Bangladesh on 687 patients from 1984 to 2004. In all cases total or near total thyroidectomy was done before commencing radioiodine therapy. Patients TG level, neck ultrasonography, thyroid scan, whole body I131 scans, neck examination were done every six monthly/yearly. Results: Among 687 patients, female were more sufferers (68.1%) and female to male ratio was 2:1. Age group 19-40 years was mostly affected (57.8%). Most common type seen was papillary carcinoma (81.8%). After ablation 100 patients did not follow-up. Total 237 patients discontinued within 4 years. Remaining 450 patients undergone regular follow-up for 5 years and more, 394 were disease free (87.6%). Total recurrence of metastasis was 23 and 12 patients expired at different times. Conclusions: Long-term regular follow-up is necessary after radioiodine ablation to become free of disease.

  18. Combined effect of brain-derived neurotrophic factor and LINGO-1 fusion protein on long-term survival of retinal ganglion cells in chronic glaucoma.

    PubMed

    Fu, Q-L; Li, X; Yip, H K; Shao, Z; Wu, W; Mi, S; So, K-F

    2009-08-18

    Glaucoma is a progressive neuropathy characterized by loss of vision as a result of retinal ganglion cell (RGC) death. There are no effective neuroprotectants to treat this disorder. Brain-derived neurotrophic factor (BDNF) is well known to transiently delay RGC death in ocular hypertensive eyes. The CNS-specific leucine-rich repeat protein LINGO-1 contributes to the negative regulation to some trophic pathways. We thereby examined whether BDNF combined with LINGO-1 antagonists can promote long-term RGC survival after ocular hypertension. In this study, intraocular pressure was elevated in adult rats using an argon laser to photocoagulate the episcleral and limbal veins. BDNF alone shows slight neuroprotection to RGCs after a long-term progress of 4 weeks following the induction of ocular hypertension. However, combination of BDNF and LINGO-1-Fc prevents RGC death in the same condition. We further identified that (1) LINGO-1 was co-expressed with BDNF receptor, TrkB in the RGCs, and (2) BDNF combined with LINGO-1-Fc activated more TrkB in the injured retina compared to BDNF alone. These results indicate that the combination of BDNF with LINGO-1 antagonist can provide long-term protection for RGCs in a chronic ocular hypertension model. TrkB may be the predominant mediator of this neuroprotection.

  19. AMPK and vacuole-associated Atg14p orchestrate µ-lipophagy for energy production and long-term survival under glucose starvation.

    PubMed

    Seo, Arnold Young; Lau, Pick-Wei; Feliciano, Daniel; Sengupta, Prabuddha; Le Gros, Mark A; Cinquin, Bertrand; Larabell, Carolyn A; Lippincott-Schwartz, Jennifer

    2017-04-10

    Dietary restriction increases the longevity of many organisms but the cell signaling and organellar mechanisms underlying this capability are unclear. We demonstrate that to permit long-term survival in response to sudden glucose depletion, yeast cells activate lipid-droplet (LD) consumption through micro-lipophagy (µ-lipophagy), in which fat is metabolized as an alternative energy source. AMP-activated protein kinase (AMPK) activation triggered this pathway, which required Atg14p. More gradual glucose starvation, amino acid deprivation or rapamycin did not trigger µ-lipophagy and failed to provide the needed substitute energy source for long-term survival. During acute glucose restriction, activated AMPK was stabilized from degradation and interacted with Atg14p. This prompted Atg14p redistribution from ER exit sites onto liquid-ordered vacuole membrane domains, initiating µ-lipophagy. Our findings that activated AMPK and Atg14p are required to orchestrate µ-lipophagy for energy production in starved cells is relevant for studies on aging and evolutionary survival strategies of different organisms.

  20. Long-term survival in laparoscopic vs open resection for colorectal liver metastases: inverse probability of treatment weighting using propensity scores

    PubMed Central

    Lewin, Joel W.; O'Rourke, Nicholas A.; Chiow, Adrian K.H.; Bryant, Richard; Martin, Ian; Nathanson, Leslie K.; Cavallucci, David J.

    2015-01-01

    Background This study compares long-term outcomes between intention-to-treat laparoscopic and open approaches to colorectal liver metastases (CLM), using inverse probability of treatment weighting (IPTW) based on propensity scores to control for selection bias. Method Patients undergoing liver resection for CLM by 5 surgeons at 3 institutions from 2000 to early 2014 were analysed. IPTW based on propensity scores were generated and used to assess the marginal treatment effect of the laparoscopic approach via a weighted Cox proportional hazards model. Results A total of 298 operations were performed in 256 patients. 7 patients with planned two-stage resections were excluded leaving 284 operations in 249 patients for analysis. After IPTW, the population was well balanced. With a median follow up of 36 months, 5-year overall survival (OS) and recurrence-free survival (RFS) for the cohort were 59% and 38%. 146 laparoscopic procedures were performed in 140 patients, with weighted 5-year OS and RFS of 54% and 36% respectively. In the open group, 138 procedures were performed in 122 patients, with a weighted 5-year OS and RFS of 63% and 38% respectively. There was no significant difference between the two groups in terms of OS or RFS. Conclusion In the Brisbane experience, after accounting for bias in treatment assignment, long term survival after LLR for CLM is equivalent to outcomes in open surgery. PMID:26902138

  1. Long term survival of HER2-positive early breast cancer treated with trastuzumab-based adjuvant regimen: a large cohort study from clinical practice.

    PubMed

    Bonifazi, Martina; Franchi, Matteo; Rossi, Marta; Zambelli, Alberto; Moja, Lorenzo; Zambon, Antonella; Corrao, Giovanni; La Vecchia, Carlo; Zocchetti, Carlo; Negri, Eva

    2014-10-01

    Trastuzumab-based regimens for the adjuvant treatment of HER2-positive early breast cancer significantly prolonged overall survival (OS) and disease free survival (DFS) in large randomized trials, with sustained benefits at four-year follow-up. We assessed long-term survival estimates and predictors in a large cohort of Italian women with early breast cancer treated with trastuzumab in clinical practice. Through a record linkage between five regional healthcare databases, we identified women treated with trastuzumab for early breast cancer in Lombardy (2006-2009). DFS and OS were estimated using the Kaplan-Meier method, and independent predictors were assessed using proportional hazard models. 2046 women received trastuzumab in early breast cancer adjuvant setting. Overall, the proportion of patients surviving free of disease was 93.9% at one year, 85.8% at 2 years, 79.4% at 3 years, and 75.0% at 4 years. OS estimates were 98.7%, 95.4%, 91.5% and 89.4% at 1, 2, 3 and 4 years, respectively. Significant independent predictors of worse survival outcomes were age <40 or ≥70 years compared to age 40-69 years, positive nodal status, radical breast surgery, combination therapy with paclitaxel, having at least one comorbidity (i.e. diabetes, cardiovascular disease), and a trastuzumab-based regimen lasting less than six months. Long term survival rates of women treated with trastuzumab for early breast cancer in clinical practice were consistent with estimates from clinical trials testing the drug in the adjuvant setting.

  2. Long-Term Survival of Borrelia burgdorferi Lacking the Hibernation Promotion Factor Homolog in the Unfed Tick Vector

    PubMed Central

    Fazzino, Lisa; Dulebohn, Daniel P.

    2015-01-01

    Borrelia burgdorferi, a causative agent of Lyme borreliosis, is a zoonotic pathogen that survives in nutrient-limited environments within a tick, prior to transmission to its mammalian host. Survival under these prolonged nutrient-limited conditions is thought to be similar to survival during stationary phase, which is characterized by growth cessation and decreased protein production. Multiple ribosome-associated proteins are implicated in stationary-phase survival of Escherichia coli. These proteins include hibernation-promoting factor (HPF), which dimerizes ribosomes and prevents translation of mRNA. Bioinformatic analyses indicate that B. burgdorferi harbors an hpf homolog, the bb0449 gene. BB0449 protein secondary structure modeling also predicted HPF-like structure and function. However, BB0449 protein was not localized in the ribosome-associated protein fraction of in vitro-grown B. burgdorferi. In wild-type B. burgdorferi, bb0449 transcript and BB0449 protein levels are low during various growth phases. These results are inconsistent with patterns of synthesis of HPF-like proteins in other bacterial species. In addition, two independently derived bb0449 mutants successfully completed the mouse-tick infectious cycle, indicating that bb0449 is not required for prolonged survival in the nutrient-limited environment in the unfed tick or any other stage of infection by B. burgdorferi. We suggest either that BB0449 is associated with ribosomes under specific conditions not yet identified or that BB0449 of B. burgdorferi has a function other than ribosome conformation modulation. PMID:26438790

  3. Long-term survival of Borrelia burgdorferi lacking the hibernation promotion factor homolog in the unfed tick vector.

    PubMed

    Fazzino, Lisa; Tilly, Kit; Dulebohn, Daniel P; Rosa, Patricia A

    2015-12-01

    Borrelia burgdorferi, a causative agent of Lyme borreliosis, is a zoonotic pathogen that survives in nutrient-limited environments within a tick, prior to transmission to its mammalian host. Survival under these prolonged nutrient-limited conditions is thought to be similar to survival during stationary phase, which is characterized by growth cessation and decreased protein production. Multiple ribosome-associated proteins are implicated in stationary-phase survival of Escherichia coli. These proteins include hibernation-promoting factor (HPF), which dimerizes ribosomes and prevents translation of mRNA. Bioinformatic analyses indicate that B. burgdorferi harbors an hpf homolog, the bb0449 gene. BB0449 protein secondary structure modeling also predicted HPF-like structure and function. However, BB0449 protein was not localized in the ribosome-associated protein fraction of in vitro-grown B. burgdorferi. In wild-type B. burgdorferi, bb0449 transcript and BB0449 protein levels are low during various growth phases. These results are inconsistent with patterns of synthesis of HPF-like proteins in other bacterial species. In addition, two independently derived bb0449 mutants successfully completed the mouse-tick infectious cycle, indicating that bb0449 is not required for prolonged survival in the nutrient-limited environment in the unfed tick or any other stage of infection by B. burgdorferi. We suggest either that BB0449 is associated with ribosomes under specific conditions not yet identified or that BB0449 of B. burgdorferi has a function other than ribosome conformation modulation.

  4. Sarcopenia is an Independent Predictor of Severe Postoperative Complications and Long-Term Survival After Radical Gastrectomy for Gastric Cancer: Analysis from a Large-Scale Cohort.

    PubMed

    Zhuang, Cheng-Le; Huang, Dong-Dong; Pang, Wen-Yang; Zhou, Chong-Jun; Wang, Su-Lin; Lou, Neng; Ma, Liang-Liang; Yu, Zhen; Shen, Xian

    2016-03-01

    Currently, the association between sarcopenia and long-term prognosis after gastric cancer surgery has not been investigated. Moreover, the association between sarcopenia and postoperative complications remains controversial. This large-scale retrospective study aims to ascertain the prevalence of sarcopenia and assess its impact on postoperative complications and long-term survival in patients undergoing radical gastrectomy for gastric cancer. From December 2008 to April 2013, the clinical data of all patients who underwent elective radical gastrectomy for gastric cancer were collected prospectively. Only patients with available preoperative abdominal CT scan within 30 days of surgery were considered for analysis. Skeletal muscle mass was determined by abdominal (computed tomography) CT scan, and sarcopenia was diagnosed by the cut-off values obtained by means of optimum stratification. Univariate and multivariate analyses evaluating risk factors of postoperative complications and long-term survival were performed. A total of 937 patients were included in this study, and 389 (41.5%) patients were sarcopenic based on the diagnostic cut-off values (34.9 cm²/m² for women and 40.8 cm²/m² for men). Sarcopenia was an independent risk factor for severe postoperative complications (OR = 3.010, P < 0.001), but not for total complications. However, sarcopenia did not show significant association with operative mortality. Moreover, sarcopenia was an independent predictor for poorer overall survival (HR = 1.653, P < 0.001) and disease-free survival (HR = 1.620, P < 0.001). Under the adjusted tumor-node-metastasis (TNM) stage, sarcopenia remained an independent risk factor for overall survival and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I. Sarcopenia is an independent predictive factor of severe postoperative complications after radical gastrectomy for gastric cancer. Moreover, sarcopenia

  5. Long-term survival using intra-aortic balloon pump and percutaneous right ventricular assist device for biventricular mechanical support of cardiogenic shock.

    PubMed

    Atwater, Brett D; Nee, Lisa M; Gimelli, Giorgio

    2008-07-01

    Right ventricular (RV) involvement in acute inferior left ventricular (LV) myocardial infarction increases the risks of cardiogenic shock and in-hospital mortality. Acutely impaired RV performance results in reduced LV preload and, in combination with impaired LV contractility, causes severely reduced LV stroke volume and cardiac output. Here we report long-term patient survival after acute biventricular myocardial infarction (MI) using simultaneous RV support with a TandemHeart percutaneous ventricular assist device (Cardiac Assist Technologies, Pittsburgh, Pennsylvania) and LV support with an intra-aortic balloon pump. Further evaluation of completely percutaneous biventricular support in acute MI is warranted.

  6. Long-Term Survival on Medical Therapy Alone after Blunt-Trauma Aortic Regurgitation: Report of a New Case with Summary of 95 Others

    PubMed Central

    Murata, Mitsushige; Mahara, Keitaro; Iwanaga, Shiro; Fukuda, Keiichi

    2016-01-01

    Aortic regurgitation resulting from blunt chest trauma has been reported only 95 times, to our knowledge. The noncoronary and right coronary cusps are the cardiac structures most often injured. Although the aortic leaflets can appear to be undamaged after nonpenetrating trauma, they can have pathologic abnormalities and insufficient function. Some cases of posttraumatic aortic regurgitation progress slowly. Aortic valve replacement is the optimal treatment. We present the case of a then-62-year-old man who has lived more than 5 years after blunt-trauma aortic regurgitation. His is the only case of long-term survival on medical therapy alone among the 96 cases summarized in this report. PMID:27777534

  7. Factors associated with long-term survival in dogs undergoing liver lobectomy as treatment for liver tumors.

    PubMed

    Kinsey, Jessica R; Gilson, Stephen D; Hauptman, Joe; Mehler, Steve J; May, Lauren R

    2015-06-01

    The objectives of the study were to describe clinicopathologic findings in dogs that underwent surgical treatment of liver tumors and to define outcome-associated variables in this canine population. Medical records of 118 dogs that underwent liver lobectomy were reviewed. Variables were assessed via univariate and multivariate Cox regression analyses. Hazard ratios, median survival times (MSTs), and Kaplan-Meier Survival curves (KMSCs) were created for significant variables. Of the dogs with surgically addressed hepatic tumors, 93% survived to discharge. The MST was not reached. Lethargic dogs had a mortality risk 10.2 times that of non-lethargic dogs. Non-tachypneic dogs had a mortality risk 4.3 times that of tachypneic dogs. Dogs that experienced anesthetic complications had a mortality risk 100 times that of dogs that did not. We conclude that the prognosis associated with liver tumors is good. Lethargy, respiratory rate, and anesthetic complications were associated with outcome.

  8. Long-term survival after coronary bypass surgery. Comparison of various subsets of patients with general population.

    PubMed Central

    Greene, D G; Bunnell, I L; Arani, D T; Schimert, G; Lajos, T Z; Lee, A B; Tandon, R N; Zimdahl, W T; Bozer, J M; Kohn, R M; Visco, J P; Dean, D C; Smith, G L

    1981-01-01

    Life-table analysis consecutive cases of isolated coronary bypass surgery at the Buffalo Hospital between 1973 and 1977 showed an estimated survival of 94 per cent at five years, equal to that of an age- and sex-matched group of the US population. Subsets of these patients divided according to sex, age, number of vessels narrowed, number of segments grafted, history of myocardial infarction, ejection fraction, and presence of unstable angina have estimated survivals not statistically less in any of these subsets than that of matched cohorts of the general population. PMID:6971646

  9. Long-term survival of decentralized axons and incorporation of satellite cells in motor neurons of rock lobsters.

    PubMed

    Atwood, H L; Dudel, J; Feinstein, N; Parnas, I

    1989-06-19

    Previous electrophysiological experiments have shown that in the abdominal extensor muscles of rock lobsters, axons which were cut in surviving animals do not degenerate peripherally for several months, but conduct action potentials and release transmitter quanta on stimulation closely distal to the scar. Electron micrographs from the axon distal to the scar (in a reliably conducting region) show invasion of the axoplasmic space by nucleated cells, probably glia. After several months, the cell membranes of the invaders have vanished and apparently functional multiple nuclei remain. We suggest that decentralized axons may survive for months with the help of 'donated' nuclei.

  10. Long-term survival in a patient with glioblastoma on antipsychotic therapy for schizophrenia: a case report and literature review

    PubMed Central

    Faraz, Shahdabul; Pannullo, Susan; Rosenblum, Marc; Smith, Andrew; Wernicke, A. Gabriella

    2016-01-01

    Glioblastoma is not only the most common primary brain tumor, but also the most aggressive. Currently, the most effective treatment of surgery, chemotherapy and radiation therapy allows for a modest median survival of 15 months. Here, we report a case of a 57-year-old male with histologically confirmed glioblastoma with unfavorable prognostic characteristics (poor performance status and persistent neurological symptoms after surgery), whose expected 5-year survival is 0%. Further genetic analysis offered a mixed prognostic picture with positive methylation of 0-6-methylguinine-DNA (deoxyribonucleic acid) methyltransferase (MGMT; favorable prognosis) and wild-type isocitrate dehydrogenase 1 (IDH-1; unfavorable prognosis). Remarkably, the patient showed a progression-free survival of 5.5 years and a total survival of 6.5 years. In the context of recently published literature, the authors hypothesize that the patient’s use of the antipsychotic medication risperidone may have had a potential antitumor effect. Risperidone antagonizes the dopamine-2 receptor and the serotonin-7 receptor, both of which have been individually implicated in the growth and progression of glioblastoma. To the authors’ knowledge, this is the first clinical case in the literature to explore this association. PMID:27800031

  11. Long-term survival after resection of a primary leiomyosarcoma of the innominate vein Report of a case.

    PubMed

    Illuminati, Giulio; Miraldi, Fabio; A Pacilè, Maria; Palumbo, Piero; Vietri, Francesco

    2012-10-29

    Leiomyosarcoma of the innominate vein is a rare but usually lethal disease. We report the case of a 50-year-old woman, undergoing a curative resection of the tumor. She is alive and free of disease at 88-month follow-up. Surgical excision remains the current optimal treatment able to provide a chance of cure. KEY WORDS: Late survival, Venous leiomyosarcoma.

  12. Long-Term survival of anoxia despite rapid ATP decline in embryos of the annual killifish Austrofundulus limnaeus.

    PubMed

    Podrabsky, Jason E; Menze, Michael A; Hand, Steven C

    2012-12-01

    Embryos of the annual killifish Austrofundulus limnaeus can survive for months in the complete absence of oxygen. Survival of anoxia is associated with entry into a state of metabolic dormancy known as diapause. However, extreme tolerance of anoxia is retained for several days of post-diapause development. Rates of heat dissipation in diapause II and 4 days post-diapause II embryos were measured under aerobic conditions and during the transition into anoxia. Phosphorylated adenylate compounds were quantified in embryos during entry into anoxia and after 12 hr of aerobic recovery. Rates of heat dissipation were not affected by exposure to anoxia in diapause II embryos, while post-diapause II embryos experienced a profound decrease in heat dissipation. ATP decreased substantially in both developmental stages upon exposure to anoxia, and all indicators of cellular energetic status indicated energetic stress, at least based on the mammalian paradigm. The rate of decline in ATP is the most acute reported for any vertebrate. The mechanisms responsible for cellular survival despite a clear dysregulation between energy production and energy consumption remain to be identified. Necrotic and apoptotic cell death in response to hypoxia contribute to poor survival during many diseases and pathological conditions in mammals. Understanding the mechanisms that are in place to prevent maladaptive cell death in embryos of A. limnaeus may greatly improve treatment strategies in diseases that involve hypoxia and reperfusion injuries.

  13. Post-transplant lymphoproliferative disorder after liver transplantation: Incidence, long-term survival and impact of serum tacrolimus level

    PubMed Central

    Eshraghian, Ahad; Imanieh, Mohammad Hadi; Dehghani, Seyed Mohsen; Nikeghbalian, Saman; Shamsaeefar, Alireza; Barshans, Frouzan; Kazemi, Kourosh; Geramizadeh, Bita; Malek-Hosseini, Seyed Ali

    2017-01-01

    AIM To investigate incidence and survival of post-transplant lymphoproliferative disorder (PTLD) patients after liver transplantation. METHODS A cross-sectional survey was conducted among patients who underwent liver transplantation at Shiraz Transplant Center (Shiraz, Iran) between August 2004 and March 2015. Clinical and laboratory data of patients were collected using a data gathering form. RESULTS There were 40 cases of PTLD in the pediatric age group and 13 cases in the adult group. The incidence of PTLD was 6.25% in pediatric patients and 1.18% in adult liver transplant recipients. The post-PTLD survival of patients at 6 mo was 75.1% ± 6%, at 1 year was 68.9% ± 6.5% and at 5 years was 39.2% ± 14.2%. Higher serum tacrolimus level was associated with lower post-PTLD survival in pediatric patients (OR = 1.07, 95%CI: 1.006-1.15, P = 0.032). A serum tacrolimus level over 11.1 ng/mL was predictive of post PTLD survival (sensitivity = 90%, specificity = 52%, area under the curve = 0.738, P = 0.035). CONCLUSION Incidence of PTLD in our liver transplant patients is comparable to other centers. Transplant physicians may consider adjustment of tacrolimus dose to maintain its serum level below this cutoff point. PMID:28275302

  14. Survival during long-term starvation: global proteomics analysis of Geobacter sulfurreducens under prolonged electron-acceptor limitation.

    PubMed

    Bansal, Reema; Helmus, Ruth A; Stanley, Bruce A; Zhu, Junjia; Liermann, Laura J; Brantley, Susan L; Tien, Ming

    2013-10-04

    The bioavailability of terminal electron acceptors (TEAs) and other substrates affects the efficiency of subsurface bioremediation. While it is often argued that microorganisms exist under "feast or famine", in the laboratory most organisms are studied under "feast" conditions, whereas they typically encounter "famine" in nature. The work described here aims to understand the survival strategies of the anaerobe Geobacter sulfurreduces under TEA-starvation conditions. Cultures were starved for TEA and at various times sampled to perform global comparative proteomic analysis using iTRAQ to obtain insight into the dynamics of change in proteins/enzymes expression associated with change in nutrient availability/environmental stress. Proteins varying in abundance with a high level of statistical significance (p < 0.05) were identified to understand how cells change from midlog to (i) stationary phase and (ii) conditions of prolonged starvation (survival phase). The most highly represented and significantly up-regulated proteins in the survival phase cells are involved in energy metabolism, cell envelope, and transport and binding functional categories. The majority of the proteins were predicted to be localized in the cell membranes. These results document that changes in the outer and cytoplasmic membranes are needed for survival of Geobacter under starvation conditions. The cell shuts down anabolic processes and becomes poised, through changes in its membrane proteins, to sense nutrients in the environment, to transport nutrients into the cell, and to detect or utilize TEAs that are encountered. Under TEA-limiting conditions, the cells turned from translucent white to red in color, indicating higher heme content. The increase in heme content supported proteomics results showing an increase in the number of cytochromes involved in membrane electron transport during the survival phase. The cell is also highly reduced with minimal change in energy charge (ATP to total

  15. Periodontal-ligament-derived stem cells exhibit the capacity for long-term survival, self-renewal, and regeneration of multiple tissue types in vivo.

    PubMed

    Menicanin, Danijela; Mrozik, Krzysztof Marek; Wada, Naohisa; Marino, Victor; Shi, Songtao; Bartold, P Mark; Gronthos, Stan

    2014-05-01

    Primary periodontal ligament stem cells (PDLSCs) are known to possess multidifferentiation potential and exhibit an immunophenotype similar to that described for bone-marrow-derived mesenchymal stem cells. In the present study, bromo-deoxyuridine (BrdU)-labeled ovine PDLSCs implanted into immunodeficient mice survived after 8 weeks post-transplantation and exhibited the capacity to form bone/cementum-like mineralized tissue, ligament structures similar to Sharpey's fibers with an associated vasculature. To evaluate self-renewal potential, PDLSCs were recovered from harvested primary transplants 8 weeks post-transplantation that exhibit an immunophenotype and multipotential capacity comparable to primary PDLSCs. The re-derived PDLSCs isolated from primary transplants were implanted into secondary ectopic xenogeneic transplants. Histomorphological analysis demonstrated that four out of six donor re-derived PDLSC populations displayed a capacity to survive and form fibrous ligament structures and mineralized tissues associated with vasculature in vivo, although at diminished levels in comparison to primary PDLSCs. Further, the capacity for long-term survival and the potential role of PDLSCs in dental tissue regeneration were determined using an ovine preclinical periodontal defect model. Autologous ex vivo-expanded PDLSCs that were prelabeled with BrdU were seeded onto Gelfoam(®) scaffolds and then transplanted into fenestration defects surgically created in the periodontium of the second premolars. Histological assessment at 8 weeks post-implantation revealed surviving BrdU-positive PDLSCs associated with regenerated periodontium-related tissues, including cementum and bone-like structures. This is the first report to demonstrate the self-renewal capacity of PDLSCs using serial xenogeneic transplants and provides evidence of the long-term survival and tissue contribution of autologous PDLSCs in a preclinical periodontal defect model.

  16. Pulmonary Tumor Thrombotic Microangiopathy Caused by a Parotid Tumor: Early Antemortem Diagnosis and Long-term Survival

    PubMed Central

    Toyonaga, Haruka; Tsuchiya, Michiko; Sakaguchi, Chikara; Ajimizu, Hitomi; Nakanishi, Yosuke; Nishiyama, Seiya; Morikawa, Noboru; Hayashi, Yasuyuki; Nagasaka, Yukio; Yasui, Hiroshi

    2017-01-01

    Pulmonary tumor thrombotic microangiopathy (PTTM) is a high-mortality disease that is difficult to diagnose clinically. Our patient was an 80-year-old woman who came to us due to symptoms of increasing dyspnea. A clinical evaluation showed that she had hypoxemia and pulmonary arterial hypertension without any abnormalities in the major pulmonary arteries, bronchi, or alveoli. A lung perfusion scan showed multiple wedge-shaped perfusion defects. Further examination revealed adenocarcinoma in her right parotid gland with metastasis to the submandibular lymph nodes. We diagnosed her to have PTTM caused by a parotid tumor. The patient survived for 11 months with chemotherapy. An early antemortem diagnosis by minimally invasive examinations will help PTTM patients to survive longer. PMID:28050002

  17. Long-term survival rates of gravity-assisted, adjustable differential pressure valves in infants with hydrocephalus.

    PubMed

    Gebert, Anna-Felicitas; Schulz, Matthias; Schwarz, Karin; Thomale, Ulrich-Wilhelm

    2016-05-01

    OBJECTIVE The use of adjustable differential pressure valves with gravity-assisted units in shunt therapy of children with hydrocephalus was reported to be feasible and promising as a way to avoid chronic overdrainage. In this single-center study, the authors' experiences in infants, who have higher rates of shunt complications, are presented. METHODS All data were collected from a cohort of infants (93 patients [37 girls and 56 boys], less than 1 year of age [mean age 4.1 ± 3.1 months]) who received their first adjustable pressure hydrocephalus shunt as either a primary or secondary implant between May 2007 and April 2012. Rates of valve and shunt failure were recorded for a total of 85 months until the end of the observation period in May 2014. RESULTS During a follow-up of 54.2 ± 15.9 months (range 26-85 months), the Kaplan-Meier rate of shunt survival was 69.2% at 1 year and 34.1% at 85 months; the Kaplan-Meier rate of valve survival was 77.8% at 1 year and 56% at 85 months. Survival rates of the shunt were significantly inferior if the patients had previous shunt surgery. During follow-up, 44 valves were exchanged in cases of infection (n = 19), occlusion (n = 14), dysfunction of the adjustment unit (n = 10), or to change the gravitational unit (n = 1). CONCLUSIONS Although a higher shunt complication rate is observed in infant populations compared with older children, reasonable survival rates demonstrate the feasibility of using this sophisticated valve technology. The gravitational unit of this valve is well tolerated and its adjustability offers the flexible application of opening pressure in an unpredictable cohort of patients. This may adequately address overdrainage-related complications from early in treatment.

  18. Long-term disease-free survival after surgical resection for multiple bone metastases from rectal cancer.

    PubMed

    Choi, Seok Jin; Kim, Jong Hun; Lee, Min Ro; Lee, Chang Ho; Kuh, Ja Hong; Kim, Jung Ryul

    2011-08-10

    Bone metastasis of primary colorectal cancer is uncommon. When it occurs, it is usually a late manifestation of disease and is indicative of poor prognosis. We describe a patient with multiple metachronous bone metastases from lower rectal cancer who was successfully treated with multimodal treatment including surgical resections and has shown 32 mo disease-free survival. Surgical resection of metastatic bone lesion(s) from colorectal cancer may be a good treatment option in selected patients.

  19. Long-term vascular access ports as a means of sedative administration in a rodent fMRI survival model.

    PubMed

    Hettinger, Patrick C; Li, Rupeng; Yan, Ji-Geng; Matloub, Hani S; Cho, Younghoon R; Pawela, Christopher P; Rowe, Daniel B; Hyde, James S

    2011-09-15

    The purpose of this study is to develop a rodent functional magnetic resonance imaging (fMRI) survival model with the use of heparin-coated vascular access devices. Such a model would ease the administration of sedative agents, reduce the number of animals required in survival experiments and eliminate animal-to-animal variability seen in previous designs. Seven male Sprague-Dawley rats underwent surgical placement of an MRI-compatible vascular access port, followed by implantable electrode placement on the right median nerve. Functional MRI during nerve stimulation and resting-state functional connectivity MRI (fcMRI) were performed at times 0, 2, 4, 8 and 12 weeks postoperatively using a 9.4T scanner. Anesthesia was maintained using intravenous dexmedetomidine and reversed using atipamezole. There were no fatalities or infectious complications during this study. All vascular access ports remained patent. Blood oxygen level dependent (BOLD) activation by electrical stimulation of the median nerve using implanted electrodes was seen within the forelimb sensory region (S1FL) for all animals at all time points. The number of activated voxels decreased at time points 4 and 8 weeks, returning to a normal level at 12 weeks, which is attributed to scar tissue formation and resolution around the embedded electrode. The applications of this experiment extend far beyond the scope of peripheral nerve experimentation. These vascular access ports can be applied to any survival MRI study requiring repeated medication administration, intravenous contrast, or blood sampling.

  20. Immediate and Long-Term Effects of a Cognitive Intervention on Intelligence, Self-Regulation, and Academic Achievement

    ERIC Educational Resources Information Center

    Sanz de Acedo Lizarraga, M. Luisa; Ugarte, M. Dolores; Iriarte, M. Dolores; Sanz de Acedo Baquedano, M. Teresa

    2003-01-01

    The main purpose of this study was to evaluate the effects of a package of activities, known as "Portfolio", on cognitive functioning, self-regulation, and academic achievement. The study was carried out with a group of 40 students from Compulsory Secondary Education (mean age 13 years old) during 120 hours distributed over two school years. A…

  1. The Long-Term Differential Achievement Effects of School Socioeconomic Composition in Primary Education: A Propensity Score Matching Approach

    ERIC Educational Resources Information Center

    Belfi, Barbara; Haelermans, Carla; De Fraine, Bieke

    2016-01-01

    Background: The effects of school socio-economic composition on student achievement growth trajectories have been a hot topic of discussion among politicians around the world for many years. However, the bulk of research investigating school socio-economic composition effects has been limited in important ways. Aims: In an attempt to overcome the…

  2. A Hybrid Adenoviral Vector System Achieves Efficient Long-Term Gene Expression in the Liver via piggyBac Transposition

    PubMed Central

    Smith, Ryan P.; Riordan, Jesse D.; Feddersen, Charlotte R.

    2015-01-01

    Abstract Much research has gone into the development of hybrid gene delivery systems that combine the broad tropism and efficient transduction of adenoviral vectors with the ability to achieve stable expression of cargo genes. In addition to gene therapy applications, such a system has considerable advantages for studies of gene function in vivo, permitting fine-tuned genetic manipulation with higher throughput than can be achieved using standard transgenic and DNA targeting techniques. Existing strategies are limited, however, by low integration efficiencies, small cargo capacity, and/or a dependence on target cell division. The utility of this approach could be enhanced by a system that provides all of the following: (1) efficient delivery, (2) stable expression in a high percentage of target cells (whether mitotic or not), (3) large cargo capacity, (4) flexibility to use with a wide range of additional experimental conditions, and (5) simple experimental technique. Here we report the initial characterization of a hybrid system that meets these criteria by utilizing piggyBac (PB) transposition to achieve genomic integration from adenoviral vectors. We demonstrate stable expression of an adenovirus (Ad)-PB-delivered reporter gene in ∼20–40% of hepatocytes following standard tail vein injection. Its high efficiency and flexibility relative to existing hybrid adenoviral gene delivery approaches indicate a considerable potential utility of the Ad-PB system for therapeutic gene delivery and in vivo studies of gene function. PMID:25808258

  3. Classifying Academically At-Risk First Graders into Engagement Types: Association with Long-Term Achievement Trajectories.

    PubMed

    Luo, Wen; Hughes, Jan N; Liew, Jeffrey; Kwok, Oiman

    2009-03-01

    Based on a sample of 480 academically at-risk first graders, we used a cluster analysis involving multimethod assessment (i.e., teacher-report, peer-evaluation, and self-report) of behavioral and psychological engagement to identify subtypes of academic engagement. Four theoretically and practically meaningful clusters were identified and labeled as cooperative (n = 95), resistive (n =96), enthusiastic (n = 188), and disaffected (n = 101). The four types did not differ in IQ measured with the Universal Nonverbal Intelligence Test. The cooperative group consisted of more female and Hispanic students, whereas the resistive group consisted of more male and African American students. The cooperative group was the most popular among peers, followed by the enthusiastic group. The disaffected and resistive groups had more emotional symptoms than the cooperative and enthusiastic groups. Academic engagement types also differed in growth trajectories of academic achievement measured with Woodcock Johnson III Tests of Achievement from second to fourth grade. For reading, the cooperative and enthusiastic groups outperformed the resistive and disaffected groups at the beginning. However, the growth rate was similar across engagement types. For math, the engagement types did not differ at the beginning. However, the cooperative group developed at a faster rate and had higher math achievement by fourth grade than the other types. The findings support the importance of teaching temperament-based regulatory skills and of providing a positive psychological climate for children's academic learning.

  4. Effect of mu Agonists on Long-Term Survival and Recurrence in Nonsmall Cell Lung Cancer Patients.

    PubMed

    Wang, Kai; Qu, Xiao; Wang, Ying; Shen, Hongchang; Liu, Qi; Du, Jiajun

    2015-08-01

    Opioids are widely used for postoperative analgesia. Morphine may have an effect on cell replication, migration, and cancer recurrence. However, the association of postoperative mu agonists with outcome of nonsmall cell lung cancer (NSCLC) patients has not been fully investigated.We retrospectively evaluated the impact of postoperative mu agonists on overall survival (OS) and disease-free survival (DFS) in early stage NSCLC patients. Patients and relevant medical information were selected from the Bio-Bank of Shandong Provincial Hospital. Difference of clinicopathologic information in postoperative mu agonists group and no mu agonists group was analyzed by χ test. Univariate and multivariate Cox regression analysis were conducted and represented as hazards ratio and 95% confidence interval form. The primary endpoint was OS and secondary endpoint was DFS.This retrospective study included 984 consecutive NSCLC patients who underwent surgery between January 2006 and December 2011. No significant difference existed between postoperative mu agonists usage group and no mu agonists usage group in clinicopathologic information except operation type (P = 0.041). Postoperative mu agonists usage was related to shorter OS (HR 1.514, 95% CI 1.197-1.916, P = 0.001) and shorter DFS (HR 1.415, 95% CI 1.123-1.781, P = 0.003) in the multivariate Cox regression model. For the patients who received postoperative chemotherapy or radiotherapy postoperative mu agonists also predict shorter survival (HR 1.437, 95% CI 1.041-1.982, P = 0.027). Subgroup analysis showed that administration of postoperative mu agonists was related to shorter OS, especially in males, more smoking, poor differential degree, bilobectomy or pneumonectomy, and stage III subgroup, respectively.Administration of postoperative mu agonists was related to shorter OS and DFS for the NSCLC patients who underwent surgery.

  5. Predictors of Long-Term Survival in Acute Coronary Syndrome Patients With Left Ventricular Dysfunction After Percutaneous Coronary Intervention

    PubMed Central

    Lee, Doo Hwan; Rhee, Jung Ae; Choi, Jin Su; Lee, Ki Hong; Lee, Min Goo; Sim, Doo Sun; Park, Keun-Ho; Yoon, Nam Sik; Yoon, Hyun Ju; Kim, Kye Hun; Park, Hyung Wook; Hong, Young Joon; Kim, Ju Han; Ahn, Youngkeun; Cho, Jeong Gwan; Park, Jong Chun; Kang, Jung Chaee

    2012-01-01

    Background and Objectives Predictive factors of mortality in acute coronary syndrome (ACS) patients with left ventricular dysfunction were analyzed during 5-year clinical follow-up after percutaneous coronary intervention (PCI). Subjects and Methods A total of 329 ACS consecutive patients (64.6±11.3 years, 227 males) who underwent PCI from January 2001 to March 2006 were followed for 5 years. All patients had lower than 40% of left ventricular ejection fraction (LVEF). Patients were divided into Group I (survived longer than 5-years: n=130, 101 males) and Group II (survived shorter than 5 years: n=199, 126 males). Results The cumulative survival rate was 88.0% at 1 month, 78.0% at 6 months, 75.0% at 1 year, 67.0% at 2 years, 62.0% at 3 years, 57.0% at 4 years and 40% at 5-years. Group II was older (61.6±11.2 years vs. 66.4±11.4 years, p<0.001), and showed higher prevalence of female gender (28.4% vs. 36.7%, p=0.006) and lower LVEF (35.3±5.2 vs. 33.6±5.6) than Group I. The independent predictors for mortality were LVEF <30% {odds ratio (OR)=1.793, 95% confidence interval (CI): 1.234-2.452, p=0.002}, serum creatinine >3.0 mg/dL (OR=2.455, 95% CI: 1.306-4.614, p=0.005), older than 65 years (OR=1.594, 95% CI: 1.152-2.206, p=0.005), and female gender (OR=1.524, 95% CI: 1.090-2.130, p=0.014). Conclusion Five-year survival rate was 40% in ACS patients with left ventricular dysfunction, and the predictors for mortality were low LVEF, high serum creatinine, old age, and female gender. PMID:23170097

  6. Long-Term Care

    MedlinePlus

    ... this page please turn Javascript on. Long-Term Care What Is Long-Term Care? Long-term care involves a variety of services ... the Escape (Esc) button on your keyboard.) Most Care Provided at Home Long-term care is provided ...

  7. Long-Term Prophylactic Antibiotic Treatment: Effects on Survival, Immunocompetence and Reproduction Success of Parasemia plantaginis (Lepidoptera: Erebidae).

    PubMed

    Dickel, Franziska; Freitak, Dalial; Mappes, Johanna

    2016-01-01

    Hundreds of insect species are nowadays reared under laboratory conditions. Rearing of insects always implicates the risk of diseases, among which microbial infections are the most frequent and difficult problems. Although there are effective prophylactic treatments, the side effects of applied antibiotics are not well understood. We examined the effect of prophylactic antibiotic treatment on the overwintering success of wood tiger moth (Parasemia plantaginis) larvae, and the postdiapause effect on their life-history traits. Four weeks before hibernation larvae were treated with a widely used antibiotic (fumagillin). We monitored moths' survival and life-history traits during the following 10 mo, and compared them to those of untreated control larvae. Prophylactic antibiotic treatment had no effect on survival but we show effects on some life-history traits by decreasing the developmental time of treated larvae. However, we also revealed relevant negative effects, as antibiotic treated individuals show a decreased number of laid eggs and also furthermore a suppressed immunocompetence. These results implicate, that a prophylactic medication can also lead to negative effects on life-history traits and reproductive success, which should be seriously taken in consideration when applying a prophylactic treatment to laboratory reared insect populations.

  8. Long-Term Prophylactic Antibiotic Treatment: Effects on Survival, Immunocompetence and Reproduction Success of Parasemia plantaginis (Lepidoptera: Erebidae)

    PubMed Central

    Dickel, Franziska; Freitak, Dalial; Mappes, Johanna

    2016-01-01

    Hundreds of insect species are nowadays reared under laboratory conditions. Rearing of insects always implicates the risk of diseases, among which microbial infections are the most frequent and difficult problems. Although there are effective prophylactic treatments, the side effects of applied antibiotics are not well understood. We examined the effect of prophylactic antibiotic treatment on the overwintering success of wood tiger moth (Parasemia plantaginis) larvae, and the postdiapause effect on their life-history traits. Four weeks before hibernation larvae were treated with a widely used antibiotic (fumagillin). We monitored moths’ survival and life-history traits during the following 10 mo, and compared them to those of untreated control larvae. Prophylactic antibiotic treatment had no effect on survival but we show effects on some life-history traits by decreasing the developmental time of treated larvae. However, we also revealed relevant negative effects, as antibiotic treated individuals show a decreased number of laid eggs and also furthermore a suppressed immunocompetence. These results implicate, that a prophylactic medication can also lead to negative effects on life-history traits and reproductive success, which should be seriously taken in consideration when applying a prophylactic treatment to laboratory reared insect populations. PMID:27271967

  9. Long-term Survival and Clinical Benefit from Adoptive T-cell Transfer in Stage IV Melanoma Patients Is Determined by a Four-Parameter Tumor Immune Signature.

    PubMed

    Melief, Sara M; Visconti, Valeria V; Visser, Marten; van Diepen, Merel; Kapiteijn, Ellen H W; van den Berg, Joost H; Haanen, John B A G; Smit, Vincent T H B M; Oosting, Jan; van der Burg, Sjoerd H; Verdegaal, Els M E

    2017-02-01

    The presence of tumor-infiltrating immune cells is associated with longer survival and a better response to immunotherapy in early-stage melanoma, but a comprehensive study of the in situ immune microenvironment in stage IV melanoma has not been performed. We investigated the combined influence of a series of immune factors on survival and response to adoptive cell transfer (ACT) in stage IV melanoma patients. Metastases of 73 stage IV melanoma patients, 17 of which were treated with ACT, were studied with respect to the number and functional phenotype of lymphocytes and myeloid cells as well as for expression of galectins-1, -3, and -9. Single factors associated with better survival were identified using Kaplan-Meier curves and multivariate Cox regression analyses, and those factors were used for interaction analyses. The results were validated using The Cancer Genome Atlas database. We identified four parameters that were associated with a better survival: CD8(+) T cells, galectin-9(+) dendritic cells (DC)/DC-like macrophages, a high M1/M2 macrophage ratio, and the expression of galectin-3 by tumor cells. The presence of at least three of these parameters formed an independent positive prognostic factor for long-term survival. Patients displaying this four-parameter signature were found exclusively among patients responding to ACT and were the ones with sustained clinical benefit. Cancer Immunol Res; 5(2); 170-9. ©2017 AACR.

  10. The predicting value of postoperative body temperature on long-term survival in patients with rectal cancer.

    PubMed

    Yu, Huichuan; Luo, Yanxin; Peng, Hui; Kang, Liang; Huang, Meijin; Luo, Shuangling; Chen, Wenhao; Yang, Zihuan; Wang, Jianping

    2015-09-01

    This study aimed to assess the association between postoperative body temperature and prognosis in patients with rectal cancer. Five hundred and seven patients with stage I to III rectal cancers were enrolled in the current study. Basal body temperature (BBT, measured at 6 am) and maximal body temperature (MBT) on each day after surgery were analyzed retrospectively. Patients were divided into two equal groups according to the median of BBT and MBT at each day. The primary end points were disease-free survival (DFS) and overall survival (OS). The univariate and multivariate analyses showed that patients with low D0-MBT (<37.4 °C) had lower 3-year DFS [adjusted hazard ratio (HR) 1.56 (95 % CI 1.08-2.24, P = 0.017)] as well as OS [adjusted HR 1.72 (95 % CI 1.05-2.82, P = 0.032)] rate as compared to those with high D0-MBT (>37.4 °C). In the subset of 318 patients with T3 stage tumor and the subgroup of 458 patients without blood transfusion as well, low D0-MBT continues to be an independent predictor of DFS/OS with an adjusted HR equal to 1.48 (95 % CI 1.02-2.24, P = 0.046)/1.68 (95 % CI 1.04-2.99, P = 0.048) and 1.45 (95 % CI 1.02-2.13, P = 0.048)/1.59 (95 % CI 1.01-2.74, P = 0.049), respectively. In addition, we found that patients have higher risk of 1-year recurrence if those were exhibiting low preoperative BBT (<36.6 °C) (17 vs. 10 %, P = 0.034). Low body temperature (D0-MBT < 37.4 °C) after surgery was an independent predictor of poor survival outcomes in patients with rectal cancer.

  11. [A case of long-term survival of liver metastasis of breast cancer successfully treated with chemotherapy and endocrine therapy].

    PubMed

    Shiba, E; Koyama, H; Sasaki, Y; Iwanaga, T; Terasawa, T; Wada, A

    1985-09-01

    A 42-year-old woman was diagnosed as having hepatic metastasis two years after radical mastectomy for breast cancer. She was initially treated with oophorectomy and cytotoxic chemotherapy, which resulted in complete regression of the lesion within two years after the start of the treatment. She remained free of the disease until the fifth year thereafter, when she again developed a metastatic lesions in her liver. Since then, she has been treated sequentially with various kinds of chemotherapy and endocrine therapy with a certain degree of response to each treatment. She has survived 12 years and three months after the development of liver metastasis. This patient is the longest survivor of hepatic metastasis from breast cancer in the Japaneses literature.

  12. Long-term survival of murine allogeneic bone marrow chimeras: effect of anti-lymphocyte serum and bone marrow dose

    SciTech Connect

    Norin, A.J.; Emeson, E.E.; Veith, F.J.

    1981-02-01

    Graft-vs-host disease (GVHD) and failure of donor stem cells to engraft permanently are two major obstacles to successful bone marrow transplantation. The effect of a single large dose of anti-lymphocyte serum (ALS) on mice receiving various numbers of H-2 incompatible bone marrow cells was evaluated. Most animals receiving lethal total body irradiation (TBI) and allogeneic marrow died within 45 days due to GVHD. Mice that were given ALS 6 to 24 h before TBI and bone marrow 24 h after irradiation survived in good health for more than 200 days. These cell preparations caused lethal GVHD in third party mice indicating that the lack of alloreactivity was specific to the strain in which the unresponsiveness was originally induced.

  13. Long-term cumulative survival and mechanical complications of single-tooth Ankylos Implants: focus on the abutment neck fractures

    PubMed Central

    2015-01-01

    PURPOSE To evaluate the cumulative survival rate (CSR) and mechanical complications of single-tooth Ankylos® implants. MATERIALS AND METHODS This was a retrospective clinical study that analyzed 450 single Ankylos® implants installed in 275 patients between December 2005 and December 2012. The main outcomes were survival results CSR and implant failure) and mechanical complications (screw loosening, fracture, and cumulative fracture rate [CFR]). The main outcomes were analyzed according to age, sex, implant length or diameter, bone graft, arch, and position. RESULTS The 8-year CSR was 96.9%. Thirteen (2.9%) implants failed because of early osseointegration failure in 3, marginal bone loss in 6, and abutment fracture in 4. Screw loosening occurred in 10 implants (2.2%), and 10 abutment fractures occurred. All abutment fractures were located in the neck, and concurrent screw fractures were observed. The CSR and rate of screw loosening did not differ significantly according to factors. The CFR was higher in middle-aged patients (5.3% vs 0.0% in younger and older patients); for teeth in a molar position (5.8% vs 0.0% for premolar or 1.1% for anterior position); and for larger-diameter implants (4.5% for 4.5 mm and 6.7% for 5.5 mm diameter vs 0.5% for 3.5 mm diameter) (all P<.05). CONCLUSION The Ankylos® implant is suitable for single-tooth restoration in Koreans. However, relatively frequent abutment fractures (2.2%) were observed and some fractures resulted in implant failures. Middle-aged patients, the molar position, and a large implant diameter were associated with a high incidence of abutment fracture. PMID:26813443

  14. Leuconostoc bacteriophages from blue cheese manufacture: long-term survival, resistance to thermal treatments, high pressure homogenization and chemical biocides of industrial application.

    PubMed

    Pujato, Silvina A; Guglielmotti, Daniela M; Ackermann, Hans-W; Patrignani, Francesca; Lanciotti, Rosalba; Reinheimer, Jorge A; Quiberoni, Andrea

    2014-05-02

    Nine Leuconostoc mesenteroides phages were isolated during blue cheese manufacture yielding faulty products with reduced eye formation. Their morphologies, restriction profiles, host ranges and long-term survival rates (25°C, 8°C, -20°C and -80°C) were analysed. Based on restriction analysis, six of them were further examined regarding resistance to physical (heat and high pressure homogenization, HPH) and chemical treatments (ethanol, sodium hypochlorite, peracetic acid, biocides A, C, E and F). According to their morphology, L. mesenteroides phages studied in the present work belonged to the Caudovirales order and Siphoviridae family. Six distinct restriction patterns were obtained with EcoRV, HindIII, ClaI and XhoI enzymes, revealing interesting phage diversity in the dairy environment. No significant reductions in phage counts were observed after ten months of storage at -20°C and -80°C, while slightly and moderate decrease in phage numbers were noticed at 8°C and 25°C, respectively. The phages subjected to heat treatments generally showed high resistance at 63°C and moderate resistance at 72°C. However, 80°C for 30 min and 90°C for 2 min led to complete inactivation of viral particles. In general, the best ethanol concentration tested was 75%, as complete inactivation for most Leuconostoc phages within 30 min of incubation was achieved. Peracetic acid, and biocides A, C, E and F were highly effective when used at the same or at a moderately lower concentration as recommended by the producer. Usually, moderate or high concentrations (600-1,600 ppm) of sodium hypochlorite were necessary to completely inactivate phage particles. Leuconostoc phages were partially inactivated by HPH treatments as remaining viral particles were found even after 8 passes at 100 MPa. This is the first report of L. mesenteroides phages isolated from an Argentinean dairy cheese plant. The results of this work could be useful for establishing the most effective physical and

  15. Parenteral adenoviral boost enhances BCG induced protection, but not long term survival in a murine model of bovine TB.

    PubMed

    Kaveh, Daryan A; Garcia-Pelayo, M Carmen; Webb, Paul R; Wooff, Esen E; Bachy, Véronique S; Hogarth, Philip J

    2016-07-25

    Boosting BCG using heterologous prime-boost represents a promising strategy for improved tuberculosis (TB) vaccines, and adenovirus (Ad) delivery is established as an efficacious boosting vehicle. Although studies demonstrate that intranasal administration of Ad boost to BCG offers optimal protection, this is not currently possible in cattle. Using Ad vaccine expressing the mycobacterial antigen TB10.4 (BCG/Ad-TB10.4), we demonstrate, parenteral boost of BCG immunised mice to induce specific CD8(+) IFN-γ producing T cells via synergistic priming of new epitopes. This induces significant improvement in pulmonary protection against Mycobacterium bovis over that provided by BCG when assessed in a standard 4week challenge model. However, in a stringent, year-long survival study, BCG/Ad-TB10.4 did not improve outcome over BCG, which we suggest may be due to the lack of additional memory cells (IL-2(+)) induced by boosting. These data indicate BCG-prime/parenteral-Ad-TB10.4-boost to be a promising candidate, but also highlight the need for further understanding of the mechanisms of T cell priming and associated memory using Ad delivery systems. That we were able to generate significant improvement in pulmonary protection above BCG with parenteral, rather than mucosal administration of boost vaccine is critical; suggesting that the generation of effective mucosal immunity is possible, without the risks and challenges of mucosal administration, but that further work to specifically enhance sustained protective immunity is required.

  16. Long-term survivability of riprap for armoring uranium-mill tailings and covers: a literature review. [203 references

    SciTech Connect

    Lindsey, C.G.; Long, L.W.; Begej, C.W.

    1982-06-01

    Pacific Northwest Laboratory (PNL) is investigating the use of a rock armoring blanket (riprap) to mitigate wind and water erosion of an earthen radon suppression cover applied to uranium mill tailings. Because the radon suppression cover and the tailings must remain intact for up to 1000 years or longer, the riprap must withstand natural weathering forces. This report is a review of information on rock weathering and riprap durability. Chemical and physical weathering processes, rock characteristics related to durability, climatic conditions affecting the degree and rate of weathering, and testing procedures used to measure weathering susceptibilities have been reviewed. Sampling and testing techniques, as well as analyses of physical and chemical weathering susceptibilities, are necessary to evaluate rock durability. Many potential riprap materials may not be able to survive 1000 years of weathering. Available techniques for durability testing cannot adequately predict rock durability for the 1000-year period because they do not consider the issue of time (i.e., how long must riprap remain stable). This report includes an Appendix, which discusses rock weathering, written by Dr. Richard Jahns of Stanford University.

  17. Long-term survival in TARP syndrome and confirmation of RBM10 as the disease-causing gene.

    PubMed

    Gripp, Karen W; Hopkins, Elizabeth; Johnston, Jennifer J; Krause, Caitlin; Dobyns, William B; Biesecker, Leslie G

    2011-10-01

    TARP syndrome, comprising Talipes equinovarus, atrial septal defect (ASD), Robin sequence (micrognathia, glossoptosis, and cleft palate), and persistence of the left superior vena cava, is an X-linked condition with pre- or postnatal lethality in affected males. Based on linkage studies and massively parallel sequencing of X-chromosome exons in two families, the disease-causing gene was identified as RBM10. We identified a maternally inherited frameshift mutation in an unrelated patient, confirming RBM10 as the disease gene. This is the first reported individual with TARP syndrome who survived past early infancy, thus expanding the phenotypic spectrum of this disorder. In addition to the characteristic cleft palate, ASD, and persistent superior vena cava, he had low-set and posteriorly angulated ears, upslanting palpebral fissures, cryptorchidism, and structural brain abnormalities including partial agenesis of the corpus callosum, dysplastic enlarged caudate, and cerebellar hypoplasia with megacisterna magna. Preterm delivery, suspected pulmonary hypoplasia, and pulmonary hypertension resulted in chronic lung disease. At the age of 3(7)/(12) years, he remained ventilator-dependent at night, and he was fed exclusively through a gastro-jejunal tube. Sensorineural hearing loss required a hearing aid. Optic atrophy and cortical visual impairment were noted. He was unable to sit independently, was non-communicative and he had severe intellectual disability. Atrial flutter required recurrent ablation of intra-atrial re-entry pathways. The mother's heterozygosity for the RBM10 mutation underscored the importance of accurate diagnosis and counseling for TARP syndrome.

  18. Short-term surgical and long-term survival outcomes after laparoscopic distal gastrectomy with D2 lymphadenectomy for gastric cancer

    PubMed Central

    2014-01-01

    Background Laparoscopic distal gastrectomy (LDG) for gastric cancer has gradually gained popularity. However, the long-term oncological outcomes of LDG have rarely been reported. This study aimed to investigate the survival outcomes of LDG, and evaluate the early surgical outcomes of laparoscopy-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG). Methods Clinical outcomes of 240 consecutive patients with gastric cancer who underwent LDG at our institution between October 2004 and April 2013 were analyzed. Early surgical outcomes of LADG and TLDG were compared and operative experiences were evaluated. Results Of the 240 patients, 93 underwent LADG and 147 underwent TLDG. There were 109 T1, 36 T2, 31 T3, and 64 T4a lesions. The median follow-up period was 31.5 months (range: 4–106 months). Tumor recurrence was observed in 40 patients and peritoneal recurrence was observed most commonly. The 5-year disease-free survival (DFS) and overall survival (OS) rates according to tumor stage were 90.3% and 93.1% in stage I, 72.7% and 67.6% in stage II, and 34.8% and 41.5% in stage III, respectively. No significant differences in early surgical outcomes were noted such as operation time, blood loss and postoperative recovery between LADG and TLDG (P >0.05). Conclusions LDG for gastric cancer had acceptable long-term oncologic outcomes. The early surgical outcomes of the two commonly used LDG methods were similar. PMID:24568165

  19. Visual thinking networking promotes long-term meaningful learning and achievement for 9th grade earth science students

    NASA Astrophysics Data System (ADS)

    Longo, Palma Joni

    2001-12-01

    An experimental and interview-based design was used to test the efficacy of visual thinking networking (VTN), a new generation of metacognitive learning strategies. Students constructed network diagrams using semantic and figural elements to represent knowledge relationships. The findings indicated the importance of using color in VTN strategies. The use of color promoted the encoding and reconstruction of earth science knowledge in memory and enhanced higher order thinking skills of problem solving. Fifty-six ninth grade earth science students (13--15 years of age) in a suburban school district outside New York City were randomly assigned to three classes with the same instructor. Five major positive findings emerged in the areas of problem solving achievement, organization of knowledge in memory, problem solving strategy dimensionality, conceptual understanding, and gender differences. A multi-covariate analysis was conducted on the pre-post gain scores of the AGI/NSTA Earth Science Examination (Part 1). Students who used the color VTN strategies had a significantly higher mean gain score on the problem solving criterion test items than students who used the black/white VTN (p = .003) and the writing strategies for learning science (p < .001). During a think-out-loud problem solving interview, students who used the color VTN strategies: (1) significantly recalled more earth science knowledge than students who used the black/white VTN (p = .021) and the writing strategies (p < .001); (2) significantly recalled more interrelated earth science knowledge than students who used black/white VTN strategies (p = .048) and the writing strategy (p < .001); (3) significantly used a greater number of action verbs than students who used the writing strategy (p = .033). Students with low abstract reasoning aptitude who used the color VTNs had a significantly higher mean number of conceptually accurate propositions than students who used the black/white VTN (p = .018) and the

  20. Influence of blood transfusions and preoperative anemia on long-term survival in patients operated for non-small cell lung cancer.

    PubMed

    Panagopoulos, Nikolaos D; Karakantza, Marina; Koletsis, Efstratios; Apostolakis, Efstratios; Sakellaropoulos, George C; Filos, Kriton S; Eleni, Theodori; Dougenis, Dimitrios

    2008-11-01

    It has been postulated that transfusions have immunosuppressive effects that promote tumor growth and metastasis. Moreover perioperative anemia is considered an independent prognostic factor on outcome in patients operated for malignancy. We evaluated the influence of red blood cell (RBC) transfusions and perioperative anemia on survival in non-small cell lung carcinoma (NSCLC) patients. From 1999 through 2005, 331 consecutive patients, male/female=295/36 (mean age 64+/-9 years), who underwent radical surgery for NSCLC were prospectively enrolled in this cohort and followed up for a mean of 27.2 months. The overall survival of patients was analyzed in relation to RBC transfusions and perioperative anemia. These parameters were analyzed in the whole cohort of patients and separately for stage I patients. Patients were divided according to perioperative transfusion, into Group A (transfused) and Group B (non-transfused) and according to the preoperative haemoglobin (Hb) level into Group 1(Hb<12g/dl) and Group 2(Hb> or =12g/dl), respectively. The overall transfusion rate was 25.7%. Univariate analysis showed that in the whole cohort of patients overall survival was significantly shorter in Group A (mean 33.6 months, 5-year survival 25.1%) compared to Group B (mean 48.0 months, 5-year survival 37.3%) (p=0.001). It also showed that patients with preoperative Hb level <12g/dl (Group 1), (mean of 33.0 months, 5-year survival 21.3%) had shorter survival compared to Group 2 patients (mean 49.3 months and 5-year survival 40.0%), respectively (p=0.002). Multivariate analysis in the whole cohort of patients showed that preoperative anemia was an independent risk factor for survival while RBC transfusion was not. In particular for stage I patients, it was shown that RBC transfusion was an independent prognostic factor for long-term survival as detected by multivariate analysis (p=0.043), while anemia was not. RBC transfusions affect adversely the survival of stage I NSCLC

  1. Trends in clinical features, postoperative outcomes, and long-term survival for gastric cancer: a Western experience with 1,278 patients over 30 years

    PubMed Central

    2014-01-01

    Background The aim of the present study was to identify temporal trends in long-term survival and postoperative outcomes and to analyze prognostic factors influencing the prognosis of patients with gastric cancer (GC) treated in a 30-year interval in a tertiary referral Western institution. Methods Between January 1980 and December 2010, 1,278 patients who were diagnosed with GC at the Digestive Surgery Department, Catholic University of Rome, Italy, were identified. Among them, 936 patients underwent surgical resection and were included in the analysis. Results Over time there was a significant improvement in postoperative outcomes. Morbidity and mortality rates decreased to 19.4% and 1.6%, respectively, in the last decade. By contrast, the multivisceral resection rate steadily increased from 12.7% to 29.6%. The overall five-year survival rate steadily increased over time, reaching 51% in the last decade, and 64.5% for R0 resections. Multivariate analysis showed a higher probability of overall survival for early stages (I and II), extended lymphadenectomy, and R0 resections. Conclusions Over three decades there was a significant improvement in perioperative and postoperative care and a steady increase in overall survival. PMID:25030691

  2. Long-term survival following total pancreatectomy and superior mesenteric-portal vein resection for pancreatic ductal adenocarcinoma: A case report

    PubMed Central

    TONG, HAN-XING; ZHANG, LEI; RONG, YE-FEI; WANG, DAN-SONG; KUANG, TIAN TAO; XU, XUE-FENG; LOU, WEN-HUI; JIN, DA-YONG

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with few therapeutic options. At present, surgical resection remains the only potential curative treatment for PDAC. However, only 15–20% of patients with PDAC are eligible for lesion resection. Total pancreatectomy (TP) and superior mesenteric-portal vein resection (SMPVR) may increase the rate of resection of PDCA, but the effect of this approach on improving long-term patient outcomes remains controversial. The present study investigated a case of PDAC in the pancreatic neck of a male patient. The patient underwent a TP, combined with SMPVR, for a margin-negative resection. Following an uneventful post-operative recovery, the patient received adjuvant chemoradiotherapy. The patient is currently alive at six years post-surgery, with a high quality of life. Given the clinical outcome of this patient, TP combined with SMPVR may provide PDAC patients with an opportunity for long-term survival. Therefore, patients with PDAC that is believed to be unresectable based on pre-operative assessment, may benefit from TP and SMPVR. PMID:25435983

  3. Long-term Survival and Late Effects among 1-year Survivors of Second Allogeneic Hematopoietic Cell Transplantation for Relapsed Acute Leukemia and Myelodysplastic Syndromes

    PubMed Central

    Duncan, Christine N.; Majhail, Navneet S.; Brazauskas, Ruta; Wang, Zhiwei; Cahn, Jean-Yves; Frangoul, Haydar A.; Hayashi, Robert J.; Hsu, Jack W.; Kamble, Rammurti T.; Kasow, Kimberly A.; Khera, Nandita; Lazarus, Hillard M.; Loren, Alison W.; Marks, David I.; Maziarz, Richard T.; Mehta, Paulette; Myers, Kasiani C.; Norkin, Maxim; Pidala, Joseph A.; Porter, David L.; Reddy, Vijay; Saber, Wael; Savani, Bipin N.; Schouten, Harry C.; Steinberg, Amir; Wall, Donna A.; Warwick, Anne B.; Wood, William A.; Yu, Lolie C.; Jacobsohn, David A.; Sorror, Mohamed L.

    2014-01-01

    We analyzed the outcomes of patients who survived disease-free for 1-year or more following second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant following disease relapse; among these 325 survived relapse-free at 1-year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplant in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least one year were 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status prior to second HCT was significantly associated with higher risk for overall mortality (HR 1.71 for patients with disease not in complete remission prior to second HCT, P<0.01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults following second transplant. Chronic GVHD was the leading cause of non-relapse mortality followed by organ failure and infection. The cumulative incidence of developing at least one of the studied late effects at 10-years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence 22%) and cataracts (20%), and in adults were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease-free for at least 1-year, many can be expected to survive long term. However, they continue to be at risk for relapse and non-relapse morbidity and mortality. Novel approaches

  4. Recovery of polyclonal immunoglobulins one year after autologous stem cell transplantation as a long-term predictor marker of progression and survival in multiple myeloma.

    PubMed

    González-Calle, Verónica; Cerdá, Seila; Labrador, Jorge; Sobejano, Eduardo; González-Mena, Beatriz; Aguilera, Carmen; Ocio, Enrique María; Vidriales, María Belén; Puig, Noemí; Gutiérrez, Norma Carmen; Garcĺa-Sanz, Ramón; Alonso, Jose' Marĺa; López, Rosa; Aguilar, Carlos; Garcĺa de Coca, Alfonso; Hernández, Roberto; Hernández, José Mariano; Escalante, Fernando; Mateos, María-Victoria

    2017-01-25

    Immunoparesis or suppression of polyclonal immunoglobulins is a very common condition in newly diagnosed myeloma patients. However, the recovery of polyclonal immunoglobulins in the setting of immune reconstitution after autologous stem cell transplantation and its effect on outcome has not been explored to date. We conducted this study in a cohort of 295 patients who had undergone autologous transplantation. In order to explore the potential role of immunoglubulin recovery as a dynamic predictor of progression or survival after transplantation, conditional probabilities of progression-free survival and overall survival were estimated, according to immunoglobulin recovery, at different time points using a landmark approach. One year after transplant, when B-cell reconstitution is expected to be completed, among 169 patients alive and progression-free, 88 patients (52%) had recovered immunoglobulins and 81 (48%) had not. Interestingly, the group with immunoglobulin recovery had a significantly longer median progression-free survival than the group with persistent immunoparesis (median 60.4 vs. 27.9 months, respectively; hazard ratio=0.45, 95% CI: 0.31-0.66; P<0.001), and improved overall survival (11.3 vs.7.3 years; hazard ratio=0.45, 95% CI=0.27-0.74, P=0.002). Furthermore, the percentage of normal plasma cells detected by flow cytometry in the bone marrow assessed at day 100 after transplantation was associated with the immunoglobulin recovery at that time and may predict immunoglobulin recovery in the subsequent months: 9 months and 1 year. In conclusion, the recovery of polyclonal immunoglobulins 1 year after autologous transplantation in myeloma patients is an independent long-term predictor marker for progression and survival.

  5. Long-term survival and late effects among one-year survivors of second allogeneic hematopoietic cell transplantation for relapsed acute leukemia and myelodysplastic syndromes.

    PubMed

    Duncan, Christine N; Majhail, Navneet S; Brazauskas, Ruta; Wang, Zhiwei; Cahn, Jean-Yves; Frangoul, Haydar A; Hayashi, Robert J; Hsu, Jack W; Kamble, Rammurti T; Kasow, Kimberly A; Khera, Nandita; Lazarus, Hillard M; Loren, Alison W; Marks, David I; Maziarz, Richard T; Mehta, Paulette; Myers, Kasiani C; Norkin, Maxim; Pidala, Joseph A; Porter, David L; Reddy, Vijay; Saber, Wael; Savani, Bipin N; Schouten, Harry C; Steinberg, Amir; Wall, Donna A; Warwick, Anne B; Wood, William A; Yu, Lolie C; Jacobsohn, David A; Sorror, Mohamed L

    2015-01-01

    We analyzed the outcomes of patients who survived disease-free for 1 year or more after a second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant after disease relapse; among these, 325 were relapse free at 1 year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplantation in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least 1 year was 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status before second HCT was significantly associated with higher risk for overall mortality (hazard ratio, 1.71 for patients with disease not in complete remission before second HCT, P < .01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults after second transplantation. Chronic GVHD was the leading cause of nonrelapse mortality, followed by organ failure and infection. The cumulative incidence of developing at least 1 of the studied late effects within 10 years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence, 22%) and cataracts (20%); in adults they were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease free for at least 1 year, many can be expected to survive long term. However, they continue to be at risk for relapse and nonrelapse morbidity and mortality. Novel

  6. Time to retire--time to die? A prospective cohort study of the effects of early retirement on long-term survival.

    PubMed

    Brockmann, Hilke; Müller, Rolf; Helmert, Uwe

    2009-07-01

    In a long-term prospective cohort study we try to assess selective and protective impacts of early retirement on life expectancy. The results are based on the members of a compulsory German health insurance fund (Gmünder Ersatzkasse). We analyzed 88,399 men and 41,276 women who retired between the ages of 50 and 65 from January 1990 to December 2004. Our main outcome measures are hazard ratios for death adjusted for age, sex, marital and socioeconomic status, year of observation, age at retirement, hospitalization, and form of retirement scheme. We found a significantly higher mortality risk among pensioners with reduced earning capacities than among old-age pensioners who either left the labor market between the ages of 56 and 60 or between 61 and 65. The youngest male and female pensioners who left the labor market between the ages of 51 and 55 because of their reduced earning capacity faced the highest mortality risk. But healthy people who retire early do not experience shorter long-term survival than those who retire late. On the contrary, if we take into consideration the amount of days spent in hospital during the last 2 years prior to retirement, early retirement in fact lowers mortality risks significantly by 12% for men and by 23% for women. Thus with respect to mortality, early retirement reflects both selective and protective processes. First of all, individuals with poor health and lower survival chances are filtered out of the labor market. However, healthy pensioners may be protected during retirement. For the former, early retirement is a necessity, for the latter it is an asset. Pension reformers should take health differentials into consideration when cutting back pension programs and increasing retirement age.

  7. KINET: a social marketing programme of treated nets and net treatment for malaria control in Tanzania, with evaluation of child health and long-term survival.

    PubMed

    Schellenberg, J R; Abdulla, S; Minja, H; Nathan, R; Mukasa, O; Marchant, T; Mponda, H; Kikumbih, N; Lyimo, E; Manchester, T; Tanner, M; Lengeler, C

    1999-01-01

    We present a large-scale social marketing programme of insecticide-treated nets in 2 rural districts in southwestern Tanzania (population 350,000) and describe how the long-term child health and survival impact will be assessed. Formative and market research were conducted in order to understand community perceptions, knowledge, attitudes and practice with respect to the products to be socially marketed. We identified Zuia Mbu (Kiswahili for 'prevent mosquitoes') as a suitable brand name for both treated nets and single-dose insecticide treatment sachets. A mix of public and private sales outlets is used for distribution. In the first stage of a stepped introduction 31 net agents were appointed and trained in 18 villages: 15 were shop owners, 14 were village leaders, 1 was a parish priest and 1 a health worker. For net treatment 37 young people were appointed in the same villages and trained as agents. Further institutions in both districts such as hospitals, development projects and employers were also involved in distribution. Promotion for both products was intense and used a variety of channels. A total of 22,410 nets and 8072 treatments were sold during the first year: 18 months after launching, 46% of 312 families with children aged under 5 years reported that their children were sleeping under treated nets. A strong evaluation component in over 50,000 people allows assessment of the long-term effects of insecticide-treated nets on child health and survival, anaemia in pregnancy, and the costs of the intervention. This evaluation is based on cross-sectional surveys, and case-control and cohort studies.

  8. Small bowel metastasis from pancreatic cancer in a long-term survival patient with synchronous advanced malignant pleural mesothelioma: A case report and literature review

    PubMed Central

    Fasano, Morena; Corte, Carminia Maria Della; Vicidomini, Giovanni; Scotti, Valerio; Rambaldi, Pier Francesco; Fiorelli, Alfonso; Accardo, Marina; De Vita, Ferdinando; Santini, Mario; Ciardiello, Fortunato; Morgillo, Floriana

    2016-01-01

    Diffuse malignant pleural mesothelioma (MPM) is an aggressive tumor that originates from the surface of the pleura. Approximately 70% of cases are associated with chronic asbestos exposure. MPM is regarded as an incurable disease, with a median survival of ~2 years following intensive multimodality treatment. Pancreatic cancer is a malignancy also associated with a poor prognosis, with only 2% of patients surviving for 5 years. The majority of patients with pancreatic cancer are diagnosed with an advanced stage of disease and experience a poor response to therapy. The development of synchronous MPM and other types of cancer is rare. The present study describes a patient with synchronous, biphasic MPM and pancreatic adenocarcinoma, who was treated with a multimodal therapeutic approach with stereotactic body radiation therapy. Due to a suspected diagnosis of ‘acute abdomen’, an emergency small intestine resection was performed and a subsequent diagnosis of moderately-differentiated adenocarcinoma was confirmed. During a further immunohistochemical examination, pathologists determined that the small bowel metastasis descended from pancreatic cancer. The onset of bowel metastasis is an event rarely associated with MPM, and has not been previously described in the literature for cases of pancreatic cancer. Therefore, to the best of our knowledge, the present study describes the first case of intestinal metastasis from pancreatic cancer in a long-term survival patient with biphasic MPM. PMID:28105159

  9. IL-1RAcPb signaling regulates adaptive mechanisms in neurons that promote their long-term survival following excitotoxic insults

    PubMed Central

    Gosselin, David; Bellavance, Marc-André; Rivest, Serge

    2012-01-01

    Excitotoxicity is a major component of neurodegenerative diseases and is typically accompanied by an inflammatory response. Cytokines IL-1alpha and IL-1beta are key regulators of this inflammatory response and modulate the activity of numerous cell types, including neurons. IL-1RAcPb is an isoform of IL-1RAcP expressed specifically in neurons and promotes their survival during acute inflammation. Here, we investigated in vivo whether IL-1RAcPb also promotes neuronal survival in a model of excitotoxicity. Intrastriatal injection of kainic acid (KA) in mice caused a strong induction of IL-1 cytokines mRNA in the brain. The stress response of cortical neurons at 12 h post-injection, as measured by expression of Atf3, FoxO3a, and Bdnf mRNAs, was similar in WT and AcPb-deficient mice. Importantly however, a delayed upregulation in the transcription of calpastatin was significantly higher in WT than in AcPb-deficient mice. Finally, although absence of AcPb signaling had no effect on damage to neurons in the cortex at early time points, it significantly impaired their long-term survival. These data suggest that in a context of excitotoxicity, stimulation of IL-1RAcPb signaling may promote the activity of a key neuroprotective mechanism. PMID:23423359

  10. CA 125 regression after two completed cycles of chemotherapy: lack of prediction for long-term survival in patients with advanced ovarian cancer

    PubMed Central

    Peters-Engl, C; Obermair, A; Heinzl, H; Buxbaum, P; Sevelda, P; Medl, M

    1999-01-01

    The prognostic influence of CA 125 regression between the time point before surgery and after two completed courses of chemotherapy was studied in 210 patients with advanced ovarian cancer, and was compared to other well established prognostic factors. CA 125 blood samples were collected preoperatively (CA 125 pre) and 3 months after surgery (CA 125 3 mo) (at the beginning of the 3rd cycle of chemotherapy). The parameter CA 125 regression defined as log10 (CA 125 3 mo/CA 125 pre) was used for statistical analysis. In a survival analysis using a Cox proportional hazards model, CA 125 regression (P = 0.0001), residual tumour (P = 0.0001), age (P = 0.0095) and grading (P = 0.044) were independent variables, whereas stage of disease, histology, ascites and type of surgery failed to retain significance. Using log10 (CA 125 3 mo/CA 125 pre) as simple covariate in a Cox model showed a hazard ratio of 1.70 (95% confidence interval 1.32–2.19, P = 0.0001). However, a detailed analysis of the interaction of time with the prognostic factor CA 125 regression on survival revealed a strong time-dependent effect with a hazard ratio of more than 6 immediately after two courses of chemotherapy, whereas within approximately 1 year the hazard ratio for the surviving patients dropped quickly to the neutral level of 1. In summary, CA 125 regression is an independent prognostic factor for survival of women with advanced ovarian cancer and allows an identification of a high-risk population among patients with advanced ovarian cancer. However, the discriminating power of serial CA 125 for long-term survival seems to be temporary and prediction of individual patients outcome is far less precise. © 1999 Cancer Research Campaign PMID:10574252

  11. Long-term graft survival after conversion from cyclosporin to azathioprine 1 year after renal transplantation. A prospective, randomized study from 1 to 6 years after transplantation.

    PubMed

    Pedersen, E B; Hansen, H E; Kornerup, H J; Madsen, S; Sørensen, A W

    1993-01-01

    Cyclosporin has improved graft survival after renal transplantation, but cyclosporin nephrotoxicity is a severe clinical problem. Conversion from cyclosporin to azathioprine 1 year after transplantation might improve long-term graft survival by avoidance of cyclosporin nephrotoxicity. After treatment with cyclosporin and prednisolone during the first year after renal transplantation, 106 patients were consecutively randomized to treatment with either azathioprine and prednisolone or cyclosporin and prednisolone in a prospective, controlled study during the following 5 years, i.e. 6 years after transplantation. Actuarial estimates of graft survival rates after inclusion in the study were obtained by the product-limit method of Kaplan-Meier, and the Mantel-Cox log rank test was used to compare the two treatment regimens. When the end-points in the analyses were cessation of graft function or withdrawal of immunosuppressive treatment due to side-effects, and when patients alive with graft function or who had died with a functioning graft were treated as censored observations, graft survival 5 years after inclusion in the study was 57.7 +/- 5.2% in the total material and was the same in both the azathioprine group (52.4 +/- 7.7%) and the cyclosporin group (63.3 +/- 6.7%) (log rank = 0.40, P = 0.53). When cessation of graft function was the only end-point, graft survival 5 years after inclusion in the study was 73.7 +/- 5.2% for the total material with no significant differences between the two groups (log rank = 0.58, P = 0.45).(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Methodology to predict long-term cancer survival from short-term data using Tobacco Cancer Risk and Absolute Cancer Cure models

    NASA Astrophysics Data System (ADS)

    Mould, R. F.; Lederman, M.; Tai, P.; Wong, J. K. M.

    2002-11-01

    Three parametric statistical models have been fully validated for cancer of the larynx for the prediction of long-term 15, 20 and 25 year cancer-specific survival fractions when short-term follow-up data was available for just 1-2 years after the end of treatment of the last patient. In all groups of cases the treatment period was only 5 years. Three disease stage groups were studied, T1N0, T2N0 and T3N0. The models are the Standard Lognormal (SLN) first proposed by Boag (1949 J. R. Stat. Soc. Series B 11 15-53) but only ever fully validated for cancer of the cervix, Mould and Boag (1975 Br. J. Cancer 32 529-50), and two new models which have been termed Tobacco Cancer Risk (TCR) and Absolute Cancer Cure (ACC). In each, the frequency distribution of survival times of defined groups of cancer deaths is lognormally distributed: larynx only (SLN), larynx and lung (TCR) and all cancers (ACC). All models each have three unknown parameters but it was possible to estimate a value for the lognormal parameter S a priori. By reduction to two unknown parameters the model stability has been improved. The material used to validate the methodology consisted of case histories of 965 patients, all treated during the period 1944-1968 by Dr Manuel Lederman of the Royal Marsden Hospital, London, with follow-up to 1988. This provided a follow-up range of 20- 44 years and enabled predicted long-term survival fractions to be compared with the actual survival fractions, calculated by the Kaplan and Meier (1958 J. Am. Stat. Assoc. 53 457-82) method. The TCR and ACC models are better than the SLN model and for a maximum short-term follow-up of 6 years, the 20 and 25 year survival fractions could be predicted. Therefore the numbers of follow-up years saved are respectively 14 years and 19 years. Clinical trial results using the TCR and ACC models can thus be analysed much earlier than currently possible. Absolute cure from cancer was also studied, using not only the prediction models which

  13. Long-term follow-up of myelodysplastic syndrome patients with moderate/severe anaemia receiving human recombinant erythropoietin + 13-cis-retinoic acid and dihydroxylated vitamin D3: independent positive impact of erythroid response on survival.

    PubMed

    Crisà, Elena; Foli, Cristina; Passera, Roberto; Darbesio, Antonella; Garvey, Kimberly B; Boccadoro, Mario; Ferrero, Dario

    2012-07-01

    We previously reported a 60% erythroid response rate with recombinant erythropoietin + 13-cis retinoic acid + dihydroxylated vitamin D3 in 63 elderly myelodysplastic patients (median age 75 years) with unfavourable features for response to erythropoietin alone [70% transfusion-dependent, 35% refractory anaemia with ring sideroblasts/refractory anaemia with excess of blasts type 1 (RAEB1), 70% with International Prognostic Scoring System (IPSS) Intermediate-1 or -2]. This report updates that case study at a 7-year follow-up, and compared the impact on overall survival of erythroid response to known prognostic factors. The erythroid response duration (median 17 months; 22 in non-RAEB patients, with 20% patients in response after 6 years of therapy) was longer than in most studies with erythropoietin alone. Overall survival (median 55 months in non-RAEB, 15 in RAEB1 patients) was negatively affected by RAEB1 diagnosis, IPSS and WPSS intermediate scores and transfusion-dependence. In the multivariate analysis, erythroid response maintained an independent positive impact on survival, particularly in non-RAEB patients in the first 3 years from diagnosis (90% survival compared to 50% of non-responders). In conclusion, the long-term follow-up confirmed the achievement, by our combined treatment, of fairly long-lasting erythroid response in the majority of MDS patients with unfavourable prognostic features for response to erythropoietin: this translated in a survival benefit that was independent from other prognostic features.

  14. Long-term mortality in mothers with perinatal losses and risk modification by surviving children and attained education: a population-based cohort study

    PubMed Central

    Halland, Frode; Morken, Nils-Halvdan; DeRoo, Lisa A; Klungsøyr, Kari; Wilcox, Allen J; Skjærven, Rolv

    2016-01-01

    Objective To assess the association between perinatal losses and mother's long-term mortality and modification by surviving children and attained education. Design A population-based cohort study. Setting Norwegian national registries. Participants We followed 652 320 mothers with a first delivery from 1967 and completed reproduction before 2003, until 2010 or death. We excluded mothers with plural pregnancies, without information on education (0.3%) and women born outside Norway. Main outcome measures Main outcome measures were age-specific (40–69 years) cardiovascular and non-cardiovascular mortality. We calculated mortality in mothers with perinatal losses, compared with mothers without, and in mothers with one loss by number of surviving children in strata of mothers’ attained education (<11 years (low), ≥11 years (high)). Results Mothers with perinatal losses had increased crude mortality compared with mothers without; total: HR 1.3 (95% CI 1.3 to 1.4), cardiovascular: HR 1.8 (1.5 to 2.1), non-cardiovascular: HR 1.3 (1.2 to 1.4). Childless mothers with one perinatal loss had increased mortality compared with mothers with one child and no loss; cardiovascular: low education HR 2.7 (1.7 to 4.3), high education HR 0.91 (0.13 to 6.5); non-cardiovascular: low education HR 1.6 (1.3 to 2.2), high education HR 1.8 (1.1 to 2.9). Mothers with one perinatal loss, surviving children and high education had no increased mortality, whereas corresponding mothers with low education had increased mortality; cardiovascular: two surviving children HR 1.7 (1.2 to 2.4), three or more surviving children HR 1.6 (1.1 to 2.4); non-cardiovascular: one surviving child HR 1.2 (1.0 to 1.5), two surviving children HR 1.2 (1.1 to 1.4). Conclusions Irrespective of education, we find excess mortality in childless mothers with a perinatal loss. Increased mortality in mothers with one perinatal loss and surviving children was limited to mothers with low education. PMID:27884847

  15. Vitamin C targets (p)ppGpp synthesis leading to stalling of long-term survival and biofilm formation in Mycobacterium smegmatis.

    PubMed

    Syal, Kirtimaan; Bhardwaj, Neerupma; Chatterji, Dipankar

    2017-01-01

    Earlier, vitamin C was demonstrated to sterilize Mycobacterium tuberculosis culture via Fenton's reaction at high concentration. It alters the regulatory pathways associated with stress response and dormancy. Since (p)ppGpp is considered to be the master regulator of stress response and is responsible for bacterial survival under stress, we tested the effect of vitamin C on the formation of (p)ppGpp. In vivo estimation of (p)ppGpp showed a decrease in (p)ppGpp levels in vitamin C-treated M. smegmatis cells in comparison to the untreated cells. Furthermore, in vitro (p)ppGpp synthesis using RelMSM enzyme was conducted in order to confirm the specificity of the inhibition in the presence of variable concentrations of vitamin C. We observed that vitamin C at high concentration can inhibit the synthesis of (p)ppGpp. We illustrated binding of vitamin C to RelMSM by isothermal titration calorimetry. Enzyme kinetics was followed where K0.5 was found to be increased with the concomitant reduction of Vmax value suggesting mixed inhibition. Both long-term survival and biofilm formation were inhibited by vitamin C. The experiments suggest that vitamin C has the potential to be developed as the inhibitor of (p)ppGpp synthesis and stress response, at least in the concentration range used here.

  16. Long-term changes in food availability mediate the effects of temperature on growth, development and survival in striped marsh frog larvae: implications for captive breeding programmes.

    PubMed

    Courtney Jones, Stephanie K; Munn, Adam J; Penman, Trent D; Byrne, Phillip G

    2015-01-01

    Food availability and temperature are known to trigger phenotypic change, but the interactive effects between these factors are only beginning to be considered. The aim of this study was to examine the independent and interactive effects of long-term stochastic food availability and water temperature on larval survivorship, growth and development of the striped marsh frog, Limnodynastes peronii. Larval L. peronii were reared in conditions of either constant or stochastic food availability and in water at three different temperatures (18, 22 and 26°C), and effects on survival, growth and development were quantified. Over the experimental period, larval growth rate was highest and survivorship lowest at the warmest temperature. However, changes in food availability mediated the effects of temperature, with slower larval growth and higher survivorship in stochastic food availability treatments. Tadpoles in the stochastic food availability treatments did not reach metamorphosis during the experimental period, suggesting that developmental stasis may have been induced by food restriction. Overall, these results demonstrate that changes in food availability alter the effects of water temperature on survival, growth and development. From an applied perspective, understanding how environmental factors interact to cause phenotypic change may assist with amphibian conservation by improving the number of tadpoles generated in captive breeding programmes.

  17. Suitability of invertebrate and vertebrate cells in a portable impedance-based toxicity sensor: temperature mediated impacts on long-term survival.

    PubMed

    Curtis, T M; Collins, A M; Gerlach, B D; Brennan, L M; Widder, M W; van der Schalie, W H; Vo, N T K; Bols, N C

    2013-10-01

    Using ECIS (electric cell-substrate impedance sensing) to monitor the impedance of vertebrate cell monolayers provides a sensitive measure of toxicity for a wide range of chemical toxicants. One major limitation to using a cell-based sensor for chemical toxicant detection in the field is the difficulty in maintaining cell viability over extended periods of time prior to use. This research was performed to identify cell lines suitable for ECIS-based toxicity sensing under field conditions. A variety of invertebrate and vertebrate cell lines were screened for their abilities to be stored for extended periods of time on an enclosed fluidic biochip with minimal maintenance. Three of the ten cell lines screened exhibited favorable portability characteristics on the biochips. Interestingly, all three cell lines were derived from ectothermic vertebrates, and the storage temperature that allowed long-term cell survival on the enclosed fluidic biochips was also at the lower end of reported body temperature for the organism, suggesting that reduced cellular metabolism may be essential for longterm survival on the biochip. Future work with the ectothermic vertebrate cells will characterize their sensitivity to a wide range of chemical toxicants to determine if they are good candidates for use in a field portable toxicity sensor.

  18. A full-length bifunctional protein involved in c-di-GMP turnover is required for long-term survival under nutrient starvation in Mycobacterium smegmatis.

    PubMed

    Bharati, Binod K; Sharma, Indra Mani; Kasetty, Sanjay; Kumar, Manish; Mukherjee, Raju; Chatterji, Dipankar

    2012-06-01

    The bacterial second messenger cyclic diguanosine monophosphate (c-di-GMP) plays an important role in a variety of cellular functions, including biofilm formation, alterations in the cell surface, host colonization and regulation of bacterial flagellar motility, which enable bacteria to survive changing environmental conditions. The cellular level of c-di-GMP is regulated by a balance between opposing activities of diguanylate cyclases (DGCs) and cognate phosphodiesterases (PDE-As). Here, we report the presence and importance of a protein, MSDGC-1 (an orthologue of Rv1354c in Mycobacterium tuberculosis), involved in c-di-GMP turnover in Mycobacterium smegmatis. MSDGC-1 is a multidomain protein, having GAF, GGDEF and EAL domains arranged in tandem, and exhibits both c-di-GMP synthesis and degradation activities. Most other proteins containing GGDEF and EAL domains have been demonstrated to have either DGC or PDE-A activity. Unlike other bacteria, which harbour several copies of the protein involved in c-di-GMP turnover, M. smegmatis has a single genomic copy, deletion of which severely affects long-term survival under conditions of nutrient starvation. Overexpression of MSDGC-1 alters the colony morphology and growth profile of M. smegmatis. In order to gain insights into the regulation of the c-di-GMP level, we cloned individual domains and tested their activities. We observed a loss of activity in the separated domains, indicating the importance of full-length MSDGC-1 for controlling bifunctionality.

  19. Pathological Complete Response and Long-Term Survival in a Very Elderly Patient after Neoadjuvant Chemotherapy for Locally Advanced, Unresectable Gastric Cancer

    PubMed Central

    Kobayashi, Mitsuyoshi; Mori, Hirohito; Ebara, Kazuo

    2014-01-01

    We address the pathological complete response and long-term survival of elderly patients after neoadjuvant chemotherapy in locally advanced, unresectable gastric cancer. An 83-year-old man was hospitalized for upper abdominal pain. Gastrointestinal endoscopy showed a large tumor spanning from the gastric angle to the antrum, and extending to the duodenum. Histological analysis of the biopsy specimen revealed a poorly differentiated adenocarcinoma. Computed tomography images showed thickening of the gastric wall and invasion of the body and head of the pancreas, but did not show distant metastases. The patient was diagnosed with unresectable gastric cancer, and was treated with neoadjuvant chemotherapy using S-1 (80 mg/m2) and paclitaxel (60 mg/m2). After the third course of chemotherapy, gastrointestinal endoscopy and abdominal computed tomography revealed a remarkable reduction in tumor size. This reduction allowed distal gastrectomy to be conducted. Histological examination of the specimen revealed no cancer cells in the primary lesion or lymph nodes. The patient was treated with adjuvant chemotherapy of oral tegafur-uracil (300 mg/day) for one year after surgery. He lived for five years after surgery without recurrence. Neoadjuvant chemotherapy using S-1 and paclitaxel is a potent strategy for improving survival in very elderly patients with unresectable gastric cancer. PMID:25298899

  20. Long-term changes in food availability mediate the effects of temperature on growth, development and survival in striped marsh frog larvae: implications for captive breeding programmes

    PubMed Central

    Courtney Jones, Stephanie K.; Munn, Adam J.; Penman, Trent D.; Byrne, Phillip G.

    2015-01-01

    Food availability and temperature are known to trigger phenotypic change, but the interactive effects between these factors are only beginning to be considered. The aim of this study was to examine the independent and interactive effects of long-term stochastic food availability and water temperature on larval survivorship, growth and development of the striped marsh frog, Limnodynastes peronii. Larval L. peronii were reared in conditions of either constant or stochastic food availability and in water at three different temperatures (18, 22 and 26°C), and effects on survival, growth and development were quantified. Over the experimental period, larval growth rate was highest and survivorship lowest at the warmest temperature. However, changes in food availability mediated the effects of temperature, with slower larval growth and higher survivorship in stochastic food availability treatments. Tadpoles in the stochastic food availability treatments did not reach metamorphosis during the experimental period, suggesting that developmental stasis may have been induced by food restriction. Overall, these results demonstrate that changes in food availability alter the effects of water temperature on survival, growth and development. From an applied perspective, understanding how environmental factors interact to cause phenotypic change may assist with amphibian conservation by improving the number of tadpoles generated in captive breeding programmes. PMID:27293714

  1. Long-term survival of the Shiga toxin-producing Escherichia coli O104:H4 outbreak strain on fenugreek seeds.

    PubMed

    Knödler, Michael; Berger, Michael; Dobrindt, Ulrich

    2016-10-01

    A major outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 occurred in Germany in 2011. The epidemiological investigation revealed that a contaminated batch of fenugreek seeds (Trigonella foenum-graecum) was the most probable source of the pathogen. It was suggested that the most probable point of contamination was prior to leaving the importer, meaning that the seed contamination with STEC O104:H4 should have happened more than one year before the seeds were used for sprout production. Here, we investigated the capacity of STEC O104:H4 and closely related pathogenic as well as non-pathogenic Escherichia coli strains for long-term survival on dry fenugreek seeds. We did not observe a superior survival capacity of STEC O104:H4 on dry seeds. For none of the strains tested cultivatable cells were found without enrichment on contaminated seeds after more than 24 weeks of storage. Our findings suggest that contamination previous to the distribution from the importer may be less likely than previously assumed. We show that seeds contaminated with E. coli in extremely high numbers can be completely sterilized by a short treatment with bleach. This simple and cheap procedure does not affect the germination capacity of the seeds and could significantly improve safety in sprout production.

  2. CspR, a Cold Shock RNA-Binding Protein Involved in the Long-Term Survival and the Virulence of Enterococcus faecalis

    PubMed Central

    Michaux, Charlotte; Martini, Cecilia; Shioya, Koki; Ahmed Lecheheb, Sandra; Budin-Verneuil, Aurélie; Cosette, Pascal; Sanguinetti, Maurizio; Hartke, Axel; Verneuil, Nicolas

    2012-01-01

    By coprecipitation, we identified RNA-binding proteins in the Gram-positive opportunistic pathogen Enterococcus faecalis known to be deficient of the RNA chaperone Hfq. In particular, we characterized one belonging to the cold shock protein (Csp) family (Ef2925) renamed CspR for cold shock protein RNA binding. Compared to the wild-type strain, the ΔcspR mutant was less virulent in an insect infection model (Galleria mellonella) and exhibited a decreased persistence in mouse kidneys and a low survival rate in peritoneal macrophages. As expected, we found that the ΔcspR mutant strain was more impaired in its growth than the parental strain under cold conditions and in its long-term survival under nutrient starvation. All these phenotypes were restored after complementation of the ΔcspR mutant. In addition, Western blot analysis showed that CspR was overexpressed under cold shock conditions and in the stationary phase. Since CspR may act as an RNA chaperone, putative targets were identified using a global proteomic approach completed with transcriptomic assays. This study revealed that 19 proteins were differentially expressed in the ΔcspR strain (9 upregulated, 10 downregulated) and that CspR mainly acted at the posttranscriptional level. These data highlight for the first time the role of the RNA-binding protein CspR as a regulator in E. faecalis and its requirement in stress response and virulence in this important human pathogen. PMID:23086208

  3. CspR, a cold shock RNA-binding protein involved in the long-term survival and the virulence of Enterococcus faecalis.

    PubMed

    Michaux, Charlotte; Martini, Cecilia; Shioya, Koki; Ahmed Lecheheb, Sandra; Budin-Verneuil, Aurélie; Cosette, Pascal; Sanguinetti, Maurizio; Hartke, Axel; Verneuil, Nicolas; Giard, Jean-Christophe

    2012-12-01

    By coprecipitation, we identified RNA-binding proteins in the Gram-positive opportunistic pathogen Enterococcus faecalis known to be deficient of the RNA chaperone Hfq. In particular, we characterized one belonging to the cold shock protein (Csp) family (Ef2925) renamed CspR for cold shock protein RNA binding. Compared to the wild-type strain, the ΔcspR mutant was less virulent in an insect infection model (Galleria mellonella) and exhibited a decreased persistence in mouse kidneys and a low survival rate in peritoneal macrophages. As expected, we found that the ΔcspR mutant strain was more impaired in its growth than the parental strain under cold conditions and in its long-term survival under nutrient starvation. All these phenotypes were restored after complementation of the ΔcspR mutant. In addition, Western blot analysis showed that CspR was overexpressed under cold shock conditions and in the stationary phase. Since CspR may act as an RNA chaperone, putative targets were identified using a global proteomic approach completed with transcriptomic assays. This study revealed that 19 proteins were differentially expressed in the ΔcspR strain (9 upregulated, 10 downregulated) and that CspR mainly acted at the posttranscriptional level. These data highlight for the first time the role of the RNA-binding protein CspR as a regulator in E. faecalis and its requirement in stress response and virulence in this important human pathogen.

  4. Diabetes mellitus may affect the long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after liver transplantation

    PubMed Central

    Zhang, Qing; Deng, Yong-Lin; Liu, Chang; Huang, Li-Hong; Shang, Lei; Chen, Xin-Guo; Wang, Le-Tian; Du, Jin-Zan; Wang, Ying; Wang, Pei-Xiao; Zhang, Hui; Shen, Zhong-Yang

    2016-01-01

    AIM To determine whether diabetes mellitus (DM) affects prognosis/recurrence after liver transplantation (LT) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS A retrospective study was conducted between January 2000 and August 2013 on 1631 patients with HBV-related HCC who underwent LT with antiviral prophylaxis. Patient data were obtained from the China Liver Transplant Registry (https://www.cltr.org/). To compare the outcomes and tumor recurrence in the HBV-related HCC patients with or without DM, statistical analyses were conducted using χ2 tests, Mann-Whitney tests, the Kaplan-Meier method, log-rank tests and multivariate step-wise Cox regression analysis. RESULTS Univariate analysis of 1631 patients who underwent LT found overall 1-, 3- and 5-year survival rates of 79%, 73% and 71% respectively in the DM patients, and 84%, 78% and 76% in the non-DM patients respectively. Overall survival rate differences after LT between the two groups were significant (P = 0.041), but recurrence-free survival rates were not (P = 0.096). By stratified analysis, the overall survival rates in DM patients for age > 50 years (P = 0.002), the presence of vascular invasion (P = 0.096), tumors ≤ 3 cm (P = 0.047), two to three tumor nodules (P = 0.007), Child-Pugh grade B (P = 0.018), and pre-LT alanine aminotransferase levels between 40 and 80 IU/L (P = 0.017) were significantly lower than in non-DM patients. Additionally, serum α-fetoprotein level > 2000 ng/mL (P = 0.052) was associated with a significant survival difference trend between DM and non-DM patients. Multivariate analysis showed that the presence of DM (P < 0.001, HR = 1.591; 95%CI: 1.239-2.041) was an independent predictor associated with poor survival after LT. CONCLUSION HBV-related HCC patients with DM have decreased long-term overall survival and poor LT outcomes. Prevention strategies for HCC patients with DM are recommended. PMID:27920478

  5. Endocrine MPA enhances the effects of TAC chemotherapy on improvement of prognosis and increase in long-term survival rates for patients with endometrial cancer.

    PubMed

    Yuan, Xiuhong; Wang, L U; Xue, Juan; Li, L I; Zhang, Jing

    2015-09-01

    The aim of the present study was to investigate the effect of taxol, adriamycin and carboplatin (TAC) chemotherapy combined with endocrine medroxyprogesterone acetate (MPA) therapy for the treatment of patients with endometrial cancer. A retrospective analysis of 124 patients with endometrial cancer was performed by dividing the cohort into an experimental and control group. The 64 patients in the experimental group received TAC and MPA chemotherapy, whereas the 60 patients in the control group were treated with TAC chemotherapy only. Tissue samples scraped from the uterus were used to extract the total proteins and RNAs for the western blot and reverse transcription-quantitative polymerase chain reaction analyses, respectively. All the patients were followed up for 20-45 months, during which time prognostic data, and one- to three-year survival rates were recorded and compared. The rate of recurrence or metastasis was significantly lower in the experimental group compared with that in the control group (P<0.05) and the three-year survival rate of the experimental group was significantly higher than that of the control group (P<0.05). Furthermore, the mean metastasis-associated 1 (MTA1) protein and RNA expression levels were significantly lower in the experimental group compared with the control group (P<0.05), exhibiting ~30 and ~15% of the levels in the control group, respectively. Therefore, a treatment strategy of TAC chemotherapy combined with endocrine MPA therapy appears to effectively improve the prognosis and increase the long-term survival rates of patients with endometrial cancer. Such an enhancing effect may be mediated by the transcriptional downregulation of MTA1 expression.

  6. Long-term survival of advanced triple-negative breast cancers with a dose-intense cyclophosphamide/anthracycline neoadjuvant regimen

    PubMed Central

    Giacchetti, S; Porcher, R; Lehmann-Che, J; Hamy, A-S; de Roquancourt, A; Cuvier, C; Cottu, P-H; Bertheau, P; Albiter, M; Bouhidel, F; Coussy, F; Extra, J-M; Marty, M; de Thé, H; Espié, M

    2014-01-01

    Background: Triple-negative (TN) breast cancers exhibit major initial responses to neoadjuvant chemotherapy, but generally have a poor outcome. Because of the lack of validated drug targets, chemotherapy remains an important therapeutic tool in these cancers. Methods: We report the survival of two consecutive series of 267 locally advanced breast cancers (LABC) treated with two different neoadjuvant regimens, either a dose-dense and dose-intense cyclophosphamide–anthracycline (AC) association (historically called SIM) or a conventional sequential association of cyclophosphamide and anthracycline, followed by taxanes (EC-T). We compared pathological responses and survival rates of these two groups and studied their association with tumours features. Results: Although the two regimens showed equivalent pathological complete response (pCR) in the whole population (16 and 12%), the SIM regimen yielded a non-statistically higher pCR rate than EC-T (48% vs 24%, P=0.087) in TN tumours. In the SIM protocol, DFS was statistically higher for TN than for non-TN patients (P=0.019), although we showed that the TN status was associated with an increased initial risk of recurrence in both regimens. This effect gradually decreased and after 2 years, TN was associated with a significantly decreased likelihood of relapse in SIM-treated LABC (hazard ratio (HR)=0.25 (95% CI: 0.07–0.86), P=0.028). Conclusions: AC dose intensification treatment is associated with a very favourable long-term survival rate in TN breast cancers. These observations call for a prospective assessment of such dose-intense AC-based regimens in locally advanced TN tumours. PMID:24569467

  7. Positive and negative early life experiences differentially modulate long term survival and amyloid protein levels in a mouse model of Alzheimer's disease

    PubMed Central

    Lesuis, Sylvie L.; Maurin, Herve; Borghgraef, Peter; Lucassen, Paul J.; Leuven, Fred Van; Krugers, Harm J.

    2016-01-01

    Stress has been implicated as a risk factor for the severity and progression of sporadic Alzheimer's disease (AD). Early life experiences determine stress responsivity in later life, and modulate age-dependent cognitive decline. Therefore, we examined whether early life experiences influence AD outcome in a bigenic mouse model which progressively develops combined tau and amyloid pathology (biAT mice). Mice were subjected to either early life stress (ELS) or to ‘positive’ early handling (EH) postnatally (from day 2 to 9). In biAT mice, ELS significantly compromised long term survival, in contrast to EH which increased life expectancy. In 4 month old mice, ELS-reared biAT mice displayed increased hippocampal Aβ levels, while these levels were reduced in EH-reared biAT mice. No effects of ELS or EH were observed on the brain levels of APP, protein tau, or PSD-95. Dendritic morphology was moderately affected after ELS and EH in the amygdala and medial prefrontal cortex, while object recognition memory and open field performance were not affected. We conclude that despite the strong transgenic background, early life experiences significantly modulate the life expectancy of biAT mice. Parallel changes in hippocampal Aβ levels were evident, without affecting cognition of young adult biAT mice. PMID:27259247

  8. Long-term survival of diffuse large B cell lymphoma of the trigeminal region extending to the Meckel's cave treated by CHASER therapy: case report.

    PubMed

    Tanaka, Toshihide; Kato, Naoki; Itoh, Kuniaki; Hasegawa, Yuzuru

    2014-01-01

    A 52-year-old man with a history of malignant lymphoma of the cecum presented with lancinating facial pain in the left. Magnetic resonance imaging (MRI) revealed a tumor in the Meckel's cave extending along the trigeminal nerve. The tumor was partially removed via left retrosigmoid lateral suboccipital craniotomy. Histological examination showed findings consistent with diffuse large B cell lymphoma, which was later confirmed to be metastatic lesion from the cecal lesion. Postoperative chemotherapy with cyclophosphamide, high dose, cytarabine, steroid (dexamethasone), etoposide, and rituximab (CHASER) followed by whole brain irradiation (30 Gy) resulted in complete remission. Although facial pain persisted, the patient's general condition remained favorable and he did not experience recurrence over the 51-month follow-up period. Histological confirmation and awareness of malignant lymphoma are very important to determine the therapeutic strategy and to avoid misdiagnosis or delayed diagnosis. Long-term survival of patients with metastatic malignant lymphoma in the Meckel's cave extending along the trigeminal nerve was very rare. In addition, metastatic malignant lymphoma in the extra-axial and peripheral nervous tissue might be different from primary central nervous system lymphoma in the white matter, since the efficacy of chemotherapeutic agents against malignant lymphomas in the extra-axial regions is not attenuated by the blood brain barrier.

  9. Long-term survival of a patient with metachronous rectal metastasis from primary cecal cancer who underwent repetitive resection and chemotherapy: a case report.

    PubMed

    Shimazaki, Jiro; Nakachi, Takeshi; Tabuchi, Takanobu; Ubukata, Hideyuki; Tabuchi, Takafumi

    2014-04-23

    There are few reported cases of colorectal metastasis from cancers of other organs, particularly other segments of the colon. Here we describe the long-term survival of a 68-year-old male patient with metachronous rectal metastasis from cecal cancer who underwent repetitive resection and chemotherapy. The patient underwent ileocecal resection and hepatectomy for cecal cancer with liver metastasis (T3, N1a, M1a, Stage IVA) in 2006. The patient subsequently underwent splenectomy for splenic metastasis in 2007. In August 2008, barium enema revealed compression of the rectal wall, and abdominal computed tomography (CT) detected a mass along the rectum extending into the pelvis. Rectal metastasis from cecal cancer was suspected and Hartmann's operation with bilateral seminal vesicle dissection was performed. Histological examination of the excised tumor revealed moderately differentiated adenocarcinoma formed in the muscularis propria of the rectum and infiltrating the connective tissue between the seminal vesicle and rectum. However, no tumor was detected in the rectal mucosa or submucosa. These histological findings supported the diagnosis of rectal metastasis from cecal cancer. The patient has been monitored at our clinic for 60 months after surgical removal of the rectal metastasis. The findings from this case should alert oncologists to the potential danger of rectal metastasis from primary colon cancer and the benefits of timely complete resection in terms of improved patient outcomes.

  10. Long-term survival of a patient with pulmonary artery intimal sarcoma after sequential metastasectomies of the thyroid and adrenal glands.

    PubMed

    Choi, Yun Mi; Jang, Eun Kyung; Ahn, Seong Hee; Jeon, Min Ji; Han, Ji Min; Kim, Seong Chul; Han, Duck Jong; Gong, Gyungyup; Kim, Tae Yong; Shong, Young Kee; Kim, Won Bae

    2013-03-01

    Cancer metastases to the thyroid or adrenal gland are uncommon. Furthermore, cases showing long-term survival after surgical resection of those metastatic tumors are rare. We report a case of pulmonary artery intimal sarcoma with metastases to the thyroid and adrenal glands sequentially that was successfully treated with sequential metastasectomies. A 62-year-old woman presented with a 4-week history of dyspnea on exertion and facial edema in November 1999. Echocardiography and chest computed tomography (CT) revealed an embolism-like mass in the pulmonary trunk. Pulmonary artery endarterectomy with pulmonary valve replacement was performed, and histopathology revealed pulmonary artery intimal sarcoma. A thyroid nodule was found by chest CT in November 2001 (2 years after initial surgery). During follow-up, this lesion showed no change, but we decided to obtain fine needle aspiration cytology (FNAC) in August 2004 (4.7 years after initial surgery). FNAC revealed atypical spindle cells suggestive of metastatic intimal sarcoma. She underwent total thyroidectomy. During follow-up, a right adrenal gland mass was detected by chest CT in March 2006 (6.3 years after initial surgery), and adrenalectomy was done, which also revealed metastatic sarcoma. She has been followed up without any evidence of recurrent disease until May 2012 (12.5 years after initial surgery).

  11. Off-pump versus on-pump coronary artery bypass grafting in octogenarians: comparison of short-term outcomes and long-term survival.

    PubMed

    Lee, Daniel C; Ramirez, Sergio A; Bacchetta, Matthew; Borer, Jeffrey S; Ko, Wilson

    2013-01-01

    Off-pump coronary artery bypass (OPCAB) has gained increasing acceptance with potential benefits for high-risk elderly patients. We report a surgeon's operative outcomes in octogenarians with an OPCAB program. Retrospective, intention-to-treat analysis of 97 consecutive octogenarians who underwent coronary bypass by a single surgeon between 1997 and 2001 before and after initiation of a multi-vessel OPCAB program was performed. OPCAB was attempted in all octogenarians. The OPCAB cohort had higher serum creatinine (OPCAB vs. pre-OPCAB: 1.30 ± 0.79 mg/dl vs. 1.08 ± 0.27, p = 0.04) and ejection fractions (52 ± 14% vs. 45 ± 11%, p = 0.02) than the pre-OPCAB cohort. The OPCAB group was more likely to require urgent/emergency surgery (63 vs. 40%, p = 0.04) and to have chronic renal insufficiency (18 vs. 3%, p = 0.05). After programmatic change to OPCAB, significant postoperative improvements were observed in the length of hospital stay (17 ± 19 vs. 8 ± 4 days, p < 0.01), duration of inotropic requirement (47 ± 70 vs. 18 ± 39 h, p < 0.04), duration of ventilator support (51 ± 54 vs. 16 ± 27 h, p < 0.01) and incidence of tracheostomy (16 vs. 3%, p < 0.02). In-hospital mortalities (3.2 vs. 2.7%), strokes (3 per group) and 5-year survival did not differ significantly (57 vs. 67%, p = 0.50, NS). Despite some higher preoperative risks, the OPCAB program demonstrated clinical benefits in octogenarians but no advantage in hospital-mortality or long-term survival.

  12. Long-Term Survival in Patients With Synchronous, Solitary Brain Metastasis From Non-Small-Cell Lung Cancer Treated With Radiosurgery

    SciTech Connect

    Flannery, Todd W.; Suntharalingam, Mohan; Regine, William F.; Chin, Lawrence S.; Krasna, Mark J.; Shehata, Michael K.; Edelman, Martin J.; Kremer, Marnie; Patchell, Roy A.; Kwok, Young

    2008-09-01

    Purpose: To report the outcome of patients with synchronous, solitary brain metastasis from non-small-cell lung cancer (NSCLC) treated with gamma knife stereotactic radiosurgery (GKSRS). Patients and Methods: Forty-two patients diagnosed with synchronous, solitary brain metastasis from NSCLC were treated with GKSRS between 1993 and 2006. The median Karnofsky performance status (KPS) was 90. Patients had thoracic Stage I-III disease (American Joint Committee on Cancer 2002 guidelines). Definitive thoracic therapy was delivered to 26/42 (62%) patients; 9 patients underwent chemotherapy and radiation, 12 patients had surgical resection, and 5 patients underwent preoperative chemoradiation and surgical resection. Results: The median overall survival (OS) was 18 months. The 1-, 2-, and 5-year actuarial OS rates were 71.3%, 34.1%, and 21%, respectively. For patients who underwent definitive thoracic therapy, the median OS was 26.4 months compared with 13.1 months for those who had nondefinitive therapy, and the 5-year actuarial OS was 34.6% vs. 0% (p < 0.0001). Median OS was significantly longer for patients with a KPS {>=}90 vs. KPS < 90 (27.8 months vs. 13.1 months, p < 0.0001). The prognostic factors significant on multivariate analysis were definitive thoracic therapy (p = 0.020) and KPS (p = 0.001). Conclusions: This is one of the largest series of patients diagnosed with synchronous, solitary brain metastasis from NSCLC treated with GKSRS. Definitive thoracic therapy and KPS significantly impacted OS. The 5-year OS of 21% demonstrates the potential for long-term survival in patients treated with GKSRS; therefore, patients with good KPS should be considered for definitive thoracic therapy.

  13. Long-term survival and regeneration of neuronal and vasculature cells inside the core region after ischemic stroke in adult mice.

    PubMed

    Jiang, Michael Qize; Zhao, Ying-Ying; Cao, Wenyuan; Wei, Zheng Zachory; Gu, Xiaohuan; Wei, Ling; Yu, Shan Ping

    2016-08-11

    Focal cerebral ischemia results in an ischemic core surrounded by the peri-infarct region (penumbra). Most research attention has been focused on penumbra while the pattern of cell fates inside the ischemic core is poorly defined. In the present investigation, we tested the hypothesis that, inside the ischemic core, some neuronal and vascular cells could survive the initial ischemic insult while regenerative niches might exist many days after stroke in the adult brain. Adult mice were subjected to focal cerebral ischemia induced by permanent occlusion of distal branches of the middle cerebral artery (MCA) plus transient ligations of bilateral common carotid artery (CCA). The ischemic insult uniformly reduced the local cerebral blood flow (LCBF) by 90%. Massive cell death occurred due to multiple mechanisms and a significant infarction was cultivated in the ischemic cortex 24 h later. Nevertheless, normal or even higher levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) persistently remained in the core tissue, some NeuN-positive and Glut-1/College IV-positive cells with intact ultrastructural features resided in the core 7-14 days post stroke. BrdU-positive but TUNEL-negative neuronal and endothelial cells were detected in the core where extensive extracellular matrix infrastructure developed. Meanwhile, GFAP-positive astrocytes accumulated in the penumbra and Iba-1-positive microglial/macrophages invaded the core several days after stroke. The long term survival of neuronal and vascular cells inside the ischemic core was also seen after a severe ischemic stroke induced by permanent embolic occlusion of the MCA. We demonstrate that a therapeutic intervention of pharmacological hypothermia could save neurons/endothelial cells inside the core. These data suggest that the ischemic core is an actively regulated brain region with residual and newly formed viable neuronal and vascular cells acutely and chronically after at

  14. Adjuvant Vaccine Immunotherapy of Resected, Clinically Node-negative Melanoma: Long-Term Outcome and Impact of HLA Class I Antigen Expression on Overall Survival

    PubMed Central

    Carson, William E.; Unger, Joseph M.; Sosman, Jeffrey A.; Flaherty, Lawrence E.; Tuthill, Ralph J.; Porter, Mark J.; Thompson, John A.; Kempf, Raymond A.; Othus, Megan; Ribas, Antoni; Sondak, Vernon K.

    2014-01-01

    Associations between HLA class I antigen expression and efficacy of a melanoma vaccine (Melacine) were initially described in stage IV melanoma. Similar associations were observed in S9035, a phase III adjuvant trial evaluating Melacine for two years versus observation in patients with stage II melanoma. This report provides long-term results. The effects of treatment on relapse-free survival (RFS) and overall survival (OS) were evaluated, and pre-specified analyses investigated associations between treatment and HLA expression. Multivariable analyses were adjusted for tumor thickness, ulceration and site, method of nodal staging and sex. P=.01 was considered significant in subset analyses to account for multiple comparisons. For the entire study population of 689 patients, there were no significant differences in RFS or OS by arm. HLA serotyping was performed on 553 (80%) patients (vaccine 294, observation 259). Among the subpopulation with HLA-A2 and/or HLA-Cw3 serotype, vaccine arm patients (n=178) had marginally improved RFS (adjusted P=.02) and significantly improved OS compared with observation arm patients (n=145), with 10-year OS of 75% and 63%, respectively (hazard ratio 0.62, 99% CI 0.37-1.02, P=.01). There was no impact of HLA-A2 and/or HLA-Cw3 expression among observation arm patients. Analysis of mature data from S9035 indicates a significant OS benefit from adjuvant vaccine therapy for HLA-A2- and/or HLA-Cw3-expressing melanoma patients. The possibility of interactions between HLA type and outcome should be considered in future immunotherapy trials. Further investigations of melanoma-associated antigens present in Melacine and presented by HLA-A2 and HLA-Cw3 may be warranted. PMID:24994597

  15. Long-term survival, prevalence, and cure of cancer: a population-based estimation for 818 902 Italian patients and 26 cancer types

    PubMed Central

    Dal Maso, L.; Guzzinati, S.; Buzzoni, C.; Capocaccia, R.; Serraino, D.; Caldarella, A.; Dei Tos, A. P.; Falcini, F.; Autelitano, M.; Masanotti, G.; Ferretti, S.; Tisano, F.; Tirelli, U.; Crocetti, E.; De Angelis, R.; Virdone, S.; Zucchetto, A.; Gigli, A.; Francisci, S.; Baili, P.; Gatta, G.; Castaing, M.; Zanetti, R.; Contiero, P.; Bidoli, E.; Vercelli, M.; Michiara, M.; Federico, M.; Senatore, G.; Pannozzo, F.; Vicentini, M.; Bulatko, A.; Pirino, D. R.; Gentilini, M.; Fusco, M.; Giacomin, A.; Fanetti, A. C.; Cusimano, R.

    2014-01-01

    Background Persons living after a cancer diagnosis represent 4% of the whole population in high-income countries. The aim of the study was to provide estimates of indicators of long-term survival and cure for 26 cancer types, presently lacking. Patients and methods Data on 818 902 Italian cancer patients diagnosed at age 15–74 years in 1985–2005 were included. Proportions of patients with the same death rates of the general population (cure fractions) and those of prevalent patients who were not at risk of dying as a result of cancer (cure prevalence) were calculated, using validated mixture cure models, by cancer type, sex, and age group. We also estimated complete prevalence, conditional relative survival (CRS), time to reach 5- and 10-year CRS >95%, and proportion of patients living longer than those thresholds. Results The cure fractions ranged from >90% for patients aged <45 years with thyroid and testis cancers to <10% for liver and pancreatic cancers of all ages. Five- or 10-year CRS >95% were both reached in <10 years by patients with cancers of the stomach, colon–rectum, pancreas, corpus and cervix uteri, brain, and Hodgkin lymphoma. For breast cancer patients, 5- and 10-year CRSs reached >95% after 19 and 25 years, respectively, and in 15 and 18 years for prostate cancer patients. Five-year CRS remained <95% for >25 years after cancer diagnosis in patients with liver and larynx cancers, non-Hodgkin lymphoma, myeloma, and leukaemia. Overall, the cure prevalence was 67% for men and 77% for women. Therefore, 21% of male and 31% of female patients had already reached 5-year CRS >95%, whereas 18% and 25% had reached 10-year CRS >95%. Conclusions A quarter of Italian cancer patients can be considered cured. This observation has a high potential impact on health planning, clinical practice, and patients' perspective. PMID:25149707

  16. Long-Term Failure Patterns and Survival in a Randomized Dose-Escalation Trial for Prostate Cancer. Who Dies of Disease?

    SciTech Connect

    Kuban, Deborah A.; Levy, Lawrence B.; Cheung, M. Rex; Lee, Andrew K.; Choi, Seungtaek; Frank, Steven; Pollack, Alan

    2011-04-01

    Purpose: To report long-term failure patterns and survival in a randomized radiotherapy dose escalation trial for prostate cancer. Materials and Methods: A total of 301 patients with Stage T1b-T3 prostate cancer treated to 70 Gy versus 78 Gy now have a median follow-up of 9 years. Failure patterns and survival were compared between dose levels. The cumulative incidence of death from prostate cancer versus other causes was examined and regression analysis was used to establish predictive factors. Results: Patients with pretreatment prostate-specific antigen (PSA) >10 ng/mL or high-risk disease had higher biochemical and clinical failures rates when treated to 70 Gy. These patients also had a significantly higher risk of dying of prostate cancer. Patients <70 years old at treatment died of prostate cancer nearly three times more frequently than of other causes when they were radiated to 70 Gy, whereas those treated to 78 Gy died of other causes more frequently. Patients age 70 or older treated to 70 Gy died of prostate cancer as often as other causes, and those receiving 78 Gy never died of prostate cancer within 10 years of follow-up. In regression analysis, factors predicting for death from prostate cancer were pretreatment PSA >10.5 ng/mL, Gleason score 9 and 10, recurrence within 2.6 years of radiation, and doubling time of <3.6 months at the time of recurrence. Conclusions: Moderate dose escalation (78 Gy) decreases biochemical and clinical failure as well as prostate cancer death in patients with pretreatment PSA >10 ng/mL or high-risk disease.

  17. Therapeutic administration of IL-15 superagonist complex ALT-803 leads to long-term survival and durable antitumor immune response in a murine glioblastoma model.

    PubMed

    Mathios, Dimitrios; Park, Chul-Kee; Marcus, Warren D; Alter, Sarah; Rhode, Peter R; Jeng, Emily K; Wong, Hing C; Pardoll, Drew M; Lim, Michael

    2016-01-01

    Glioblastoma is the most aggressive primary central nervous system malignancy with a poor prognosis in patients. Despite the need for better treatments against glioblastoma, very little progress has been made in discovering new therapies that exhibit superior survival benefit than the standard of care. Immunotherapy has been shown to be a promising treatment modality that could help improve clinical outcomes of glioblastoma patients by assisting the immune system to overcome the immunosuppressive tumor environment. Interleukin-15 (IL-15), a cytokine shown to activate several effector components of the immune system, may serve as an excellent immunotherapeutic candidate for the treatment of glioblastoma. Thus, we evaluated the efficacy of an IL-15 superagonist complex (IL-15N72D:IL-15RαSu-Fc; also known as ALT-803) in a murine GL261-luc glioblastoma model. We show that ALT-803, as a single treatment as well as in combination with anti-PD-1 antibody or stereotactic radiosurgery, exhibits a robust antitumor immune response resulting in a prolonged survival including complete remission in tumor bearing mice. In addition, ALT-803 treatment results in long-term immune memory against glioblastoma tumor rechallenge. Flow cytometric analysis of tumor infiltrating immune cells shows that ALT-803 leads to increased percentage of CD8+-cell infiltration, but not the NK cells, and IFN-γ production into the tumor microenvironment. Cell depletion studies, in accordance with the flow cytometric results, show that the ALT-803 therapeutic effect is dependent on CD4+ and CD8+ cells. These results provide a rationale for evaluating the therapeutic activity of ALT-803 against glioblastoma in the clinical setting.

  18. Stability, Survival, and Tolerability of an Auditory Osseointegrated Implant for Bone Conduction Hearing: Long-Term Follow-Up of a Randomized Controlled Trial

    PubMed Central

    den Besten, Christine A.; Stalfors, Joacim; Wigren, Stina; Blechert, Johan Ivarsson; Flynn, Mark; Eeg-Olofsson, Måns; Aggarwal, Rohini; Green, Kevin; Nelissen, Rik C.; Mylanus, Emmanuel A. M.; Hol, Myrthe K. S.

    2016-01-01

    Objective: To compare implant stability, survival, and soft tissue reactions for a novel (test) and previous generation (control) percutaneous auditory osseointegrated implant for bone conduction hearing at long-term follow-up of 5 years. Study Design: Single follow-up visit of a previously completed multicenter, randomized, controlled trial. Patients: Fifty-seven of the 77 participants of a completed randomized controlled trial on a new auditory osseointegrated implant underwent a single follow-up visit 5 years after implantation, which comprised implant stability measurements and collection of Holgers scores. Additionally, implant survival was recorded for all 77 patients from the original trial. Results: The test implant showed significantly higher implant stability quotient (ISQ) values compared with the control implant throughout the 5-year follow-up. Mean area under the curve of ISQ high from baseline to 5 years was 71.6 (standard deviation [SD] ±2.0) and 66.7 (SD ±3.4) for the test and control implant, respectively (p < 0.0001). For both implants, the mean ISQ value recorded at 5 years was higher compared with implantation (test group +2.03 [SD ±2.55, within group p < 0.0001] and control group +2.25 [SD ±4.95, within group p = 0.12]). No difference was noticed in increase from baseline between groups (p = 0.64). Furthermore, evaluation of soft tissue reactions continued to show superiority of the test implant. At the 5-year follow-up visit, one patient (2.5%) presented with a Holgers grade 2 in the test group, compared with four patients (23.5%) in the control group (p = 0.048); no patient presented with more severe soft tissue reactions. Excluding explantations, the survival rate was 95.8% for the test group and 95.0% for the control group. The corresponding rates including explantations were 93.9 and 90.0%. Conclusion: The test implant showed superiority in terms of higher mean ISQ values and less adverse soft tissue reactions, both

  19. Long-term Survival and Toxicity in Patients Treated With High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

    SciTech Connect

    Spratt, Daniel E.; Pei, Xin; Yamada, Josh; Kollmeier, Marisa A.; Cox, Brett; Zelefsky, Michael J.

    2013-03-01

    Purpose: To report long-term survival and toxicity outcomes with the use of high-dose intensity modulated radiation therapy (IMRT) to 86.4 Gy for patients with localized prostate cancer. Methods and Materials: Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified by prognostic risk group based on National Comprehensive Cancer Network risk classification criteria. A total of 587 patients (59%) were treated with neoadjuvant and concurrent androgen deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range, 1-14 years). Results: For low-, intermediate-, and high-risk groups, 7-year biochemical relapse-free survival outcomes were 98.8%, 85.6%, and 67.9%, respectively (P<.001), and distant metastasis-free survival rates were 99.4%, 94.1%, and 82.0% (P<.001), respectively. On multivariate analysis, T stage (P<.001), Gleason score (P<.001), and >50% of initial biopsy positive core (P=.001) were predictive for distant mestastases. No prostate cancer-related deaths were observed in the low-risk group. The 7-year prostate cancer-specific mortality (PCSM) rates, using competing risk analysis for intermediate- and high-risk groups, were 3.3% and 8.1%, respectively (P=.008). On multivariate analysis, Gleason score (P=.004), percentage of biopsy core positivity (P=.003), and T-stage (P=.033) were predictive for PCSM. Actuarial 7-year grade 2 or higher late gastrointestinal and genitourinary toxicities were 4.4% and 21.1%, respectively. Late grade 3 gastrointestinal and genitourinary toxicity was experienced by 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. Conclusions: This study represents the largest cohort of patients treated with high-dose radiation to 86.4 Gy, using IMRT for localized prostate cancer, with the longest follow-up to date

  20. Plasma Apolipoprotein A-V Predicts Long-term Survival in Chronic Hepatitis B Patients with Acute-on-Chronic Liver Failure

    PubMed Central

    Chen, En-Qiang; Wang, Meng-Lan; Zhang, Dong-Mei; Shi, Ying; Wu, Do-Bo; Yan, Li-Bo; Du, Ling-Yao; Zhou, Ling-Yun; Tang, Hong

    2017-01-01

    Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening condition, and the lipid metabolism disorder is common in the development of this disease. This prospective observational study aimed to define the characteristics of plasma apolipoprotein A-V (apoA-V) in long-term outcome prediction of HBV-ACLF, and a total of 330 HBV-ACLF patients were included and followed for more than 12 months. In this cohort, the 4-week, 12-week, 24-week and 48-week cumulative mortality of HBV-ACLF was 18.2%(60/330), 50.9%(168/330), 59.7%(197/330) and 63.3%(209/330), respectively. As compared to survivors, the non-survivors had significantly lower concentrations of plasma apoA-V on admission. Plasma apoA-V concentrations were positively correlated with prothrombin time activity (PTA), and negatively correlated with interleukin-10, tumor necrosis factor-α, and iMELD scores. Though plasma apoA-V, PTA, total bilirubin(TBil) and blood urea nitrogen(BUN) were all independent factors to predict one-year outcomes of HBV-ACLF, plasma apoA-V had the highest prediction accuracy. And its optimal cutoff value for one-year survival prediction was 480.00 ng/mL, which had a positive predictive value of 84.68% and a negative predictive value of 92.23%. In summary, plasma apoA-V decreases significantly in non-survivors of HBV-ACLF, and it may be regarded as a new predictive marker for the prognosis of patients with HBV-ACLF. PMID:28358016

  1. Dynamic medium containing kit ligand and follicle-stimulating hormone promotes follicular survival, activation, and growth during long-term in vitro culture of caprine preantral follicles.

    PubMed

    Lima, I M T; Celestino, J J H; Faustino, L R; Magalhães-Padilha, D M; Rossetto, R; Brito, I R; Donato, M A M; Lopes, C A P; Campello, C C; Peixoto, C A; Figueiredo, J R; Rodrigues, A P R

    2012-01-01

    The aim of this study was to evaluate the effects of a dynamic medium containing kit ligand (KL) and follicle-stimulating hormone (FSH) on the in vitro culture of caprine preantral follicles for 16 days. Ovarian fragments were cultured in α-MEM(+) containing or not containing KL (50 ng/ml) and/or FSH (50 ng/ml) added during the first (days 0-8) and/or second half (days 8-16) of the culture period. Noncultured (control) and cultured fragments were processed for histological and ultrastructural evaluation. After 1 day of culture, only the treatments performed with KL or FSH maintained a percentage of normal follicles similar to that of the control. After 16 days, all treatments using KL until day 8 (KL/KL, KL/FSH, and KL/FSH+KL) and only FSH during the entire culture period (FSH/FSH) showed higher rates of follicular survival compared to α-MEM(+) alone. After 1 and 8 days, the treatments initially cultured with KL increased the percentage of follicular activation in comparison to α-MEM(+) alone and other treatments. The highest follicular diameter after 16 days was observed in follicles cultured with KL until day 8 followed by FSH (KL/FSH). Furthermore, this treatment promoted, as early as after 1 day of culture, an increase in oocyte growth compared to α-MEM(+) alone. Ultrastructural analysis confirmed the integrity of follicles cultured in KL/FSH after 16 days. In conclusion, a dynamic medium containing KL and FSH maintained follicular integrity and promoted follicular activation and growth during the long-term in vitro culture of caprine preantral follicles.

  2. Pulmonary function changes after radiotherapy in non-small-cell lung cancer patients with long-term disease-free survival

    SciTech Connect

    Borst, Gerben R.; Jaeger, Katrien de; Belderbos, Jose; Burgers, Sjaak A.; Lebesque, Joos V. . E-mail: j.lebesque@nki.nl

    2005-07-01

    Purpose: To evaluate the changes in pulmonary function after high-dose radiotherapy (RT) for non-small-cell lung cancer in patients with a long-term disease-free survival. Methods and Materials: Pulmonary function was measured in 34 patients with inoperable non-small-cell lung cancer before RT and at 3 and 18 months of follow-up. Thirteen of these patients had a pulmonary function test (PFT) 36 months after RT. The pulmonary function parameters (forced expiratory volume in 1 s [FEV{sub 1}], diffusion capacity [T{sub lcoc}], forced vital capacity, and alveolar volume) were expressed as a percentage of normal values. Changes were expressed as relative to the pre-RT value. We evaluated the impact of chronic obstructive pulmonary disease, radiation pneumonitis, mean lung dose, and PFT results before RT on the changes in pulmonary function. Results: At 3, 18, and 36 months, a significant decrease was observed for the T{sub lcoc} (9.5%, 14.6%, and 22.0%, respectively) and the alveolar volume (5.8%, 6.6%, and 15.8%, respectively). The decrease in FEV{sub 1} was significant at 18 and 36 months (8.8% and 13.4%, respectively). No recovery of any of the parameters was observed. Chronic obstructive pulmonary disease was an important risk factor for larger PFT decreases. FEV{sub 1} and T{sub lcoc} decreases were dependent on the mean lung dose. Conclusion: A significant decrease in pulmonary function was observed 3 months after RT. No recovery in pulmonary function was seen at 18 and 36 months after RT. The decrease in pulmonary function was dependent on the mean lung dose, and patients with chronic obstructive pulmonary disease had larger reductions in the PFTs.

  3. Long Term Preservation of Digital Information.

    ERIC Educational Resources Information Center

    Lorie, Raymond A.

    The preservation of digital data for the long term presents a variety of challenges from technical to social and organizational. The technical challenge is to ensure that the information, generated today, can survive long term changes in storage media, devices, and data formats. This paper presents a novel approach to the problem. It distinguishes…

  4. Long-term parenteral nutrition

    PubMed Central

    Ladefoged, Karin; Jarnum, Stig

    1978-01-01

    Nineteen patients (11 women and eight men) aged 20-68 received long-term parenteral nutrition, mostly at home, for six to 63 months (mean 19 months). Indications for LTPN were extensive, active Crohn's disease in three patients, intestinocutaneous fistulas in three, and short-bowel syndrome in the remaining 13 patients. Subclavian or intra-atrial (Broviac) catheters were most commonly used, for which the average life was four and seven months respectively. Complications of long-term parenteral nutrition included pneumothorax in four out of 48 subclavian vein punctures. Catheter-induced thrombosis of central veins was shown by phlebography 17 times in nine patients, and eight episodes of total occlusion occurred. Two of these patients had pulmonary infarction. Nineteen episodes of catheter sepsis occurred in 11 patients, but only one was fatal. Complications related to intestinal disease included intra-abdominal abscesses and intestinal fistulas, and disturbances of liver function. Five patients died, though in only two was death related to long-term parenteral nutrition. One of these patients died from catheter sepsis, the other had subdural haematoma possibly caused by anticoagulant treatment. Eight of the 14 surviving patients still needed parenteral nutrition. All received a disability pension, but six had an acceptable quality of life with almost normal social activities. Despite problems such as difficulties in maintaining standardised infusion programmes, it was concluded that long-term parenteral nutrition at home is practicable and consistent with an acceptable quality of life. ImagesFIG 2 PMID:98199

  5. AB055. Long term NIV

    PubMed Central

    Siopi, Dimitra

    2016-01-01

    role of long term NIV remains controversial in patients with chronic hypercapnic respiratory failure attributed to COPD. This happens because RCTs haven’t been able to prove benefits in survival, although the settings used in those trials seem to be insufficient to correct hypercapnia. According to more recent data higher pressure (high-intensity NIV) with the goal of achieving normocapnia can improve exercise tolerance, quality of life and survival. Obesity hypoventilation syndrome on the other hand is gradually receiving clinical interest and is recognized as a significant cause of morbidity and mortality, with a beneficial role of NIV in improving survival, hospitalizations and health related quality of life, thus reducing healthcare cost. Despite the improved awareness of the medical world dealing with the obesity epidemic, the syndrome is still under-diagnosed. Any medical specialty should perceive the value of controlling those patients in order to offer the optimal type of mechanical ventilation, depending on the underlying type of the respiratory disorder (obstructive episodes or pure hypoventilation). Patients with congestive heart failure can suffer from central sleep apnoea, OSA and Cheyne-Stokes respiration with a negative impact in their clinical outcome. CPAP therapy is indicated in resolving obstructive apnea, but is ineffective in case of central sleep apnea or Cheyne-Stokes breathing. The initial enthusiasm for assisted servo ventilation (ASV) use in this group of patients was not confirmed by a multicentre RCT (which showed increased mortality) and this type of ventilation is no longer recommended in heart failure patients with CSA and ejection fraction <45%. Scarce data exist regarding long-term NIV in patients with Cystic Fibrosis, bronchiectasis and interstitial lung diseases .It seems though that with careful patient selection NIV can play an important role in the management of those patients, even serving as a bridge to transplantation

  6. Long-term survival of non-elderly patients with severe heart failure treated with angiotensin-converting enzyme inhibitors assessment of treatment with captopril and enalapril survival study (ACESS).

    PubMed

    Huang, Chien-Ming; Young, Mason-Shing

    2002-10-01

    The present study examined the effect of treatment with angiotensin-converting enzyme inhibitors (ACEIs) on the long-term prognosis in 119 patients with dilated cardiomyopathy (DCM). Conventional therapy was used in 29 patients and 90 patients were treated with ACEIs: 50 were taking captopril and 40 were taking enalapril; 24 were taking > or = 75 mg captopril or > or = 20 mg enalapril daily (high-dose group) and 66 patients received smaller doses (low-dose group). No significant differences between groups were detected with respect to demographics and clinical signs of congestive heart failure (CHF). During follow-up, 65 patients survived and 54 patients died: 34 patients were in group 1 and 20 patients were in the placebo group. Patients treated with ACEIs had a significantly better survival during the first to third year, but the difference was not significant between the high- and low-dose groups. Comparison of the cumulative probability of death in the enalapril and captopril groups showed a trend of significant reduction of mortality by 13% in the enalapril group (p<0.10). These data indicate that ACEIs have a beneficial effect on prolonging the short- and long-term survival in DCM patients, so it is strongly recommended that all patients with DCM should be treated with ACEIs unless contraindicated. In this study, lower doses of ACEI seemed prognostically equivalent to higher doses, and enalapril appeared to be preferable to captopril in the treatment of severe CHF. Additional prospective large studies are necessary to verify the relationship observed here between the optimal dosage as well as the duration of action of different ACEIs and their outcomes.

  7. Distinguishing Low-Risk Luminal A Breast Cancer Subtypes with Ki-67 and p53 Is More Predictive of Long-Term Survival.

    PubMed

    Lee, Se Kyung; Bae, Soo Youn; Lee, Jun Ho; Lee, Hyun-Chul; Yi, Hawoo; Kil, Won Ho; Lee, Jeong Eon; Kim, Seok Won; Nam, Seok Jin

    2015-01-01

    Overexpression of p53 is the most frequent genetic alteration in breast cancer. Recently, many studies have shown that the expression of mutant p53 differs for each subtype of breast cancer and is associated with different prognoses. In this study, we aimed to determine the suitable cut-off value to predict the clinical outcome of p53 overexpression and its usefulness as a prognostic factor in each subtype of breast cancer, especially in luminal A breast cancer. Approval was granted by the Institutional Review Board of Samsung Medical Center. We analyzed a total of 7,739 patients who were surgically treated for invasive breast cancer at Samsung Medical Center between Dec 1995 and Apr 2013. Luminal A subtype was defined as ER&PR + and HER2- and was further subclassified according to Ki-67 and p53 expression as follows: luminal A (Ki-67-,p53-), luminal A (Ki-67+, p53-), luminal A (Ki-67 -, p53+) and luminal A (Ki-67+, p53+). Low-risk luminal A subtype was defined as negative for both Ki-67 and p53 (luminal A [ki-67-, p53-]), and others subtypes were considered to be high-risk luminal A breast cancer. A cut-off value of 10% for p53 was a good predictor of clinical outcome in all patients and luminal A breast cancer patients. The prognostic role of p53 overexpression for OS and DFS was only significant in luminal A subtype. The combination of p53 and Ki-67 has been shown to have the best predictive power as calculated by the area under curve (AUC), especially for long-term overall survival. In this study, we have shown that overexpression of p53 and Ki-67 could be used to discriminate low-risk luminal A subtype in breast cancer. Therefore, using the combination of p53 and Ki-67 expression in discriminating low-risk luminal A breast cancer may improve the prognostic power and provide the greatest clinical utility.

  8. High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

    SciTech Connect

    Deeg, H.J.; Storb, R.; Weiden, P.L.; Schumacher, D.; Shulman, H.; Graham, T.; Thomas, E.D.

    1981-11-01

    Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors.

  9. Dietary Omega-3 Fatty Acid, Ratio of Omega-6 to Omega-3 Intake, Inflammation, and Survival in Long-term Hemodialysis Patients

    PubMed Central

    Noori, Nazanin; Dukkipati, Ramanath; Kovesdy, Csaba P.; Sim, John J.; Feroze, Usama; Murali, Sameer B.; Bross, Rachelle; Benner, Debbie; Kopple, Joel D; Kalantar-Zadeh, Kamyar

    2011-01-01

    Background Mortality among long-term hemodialysis patients is high, mostly attributed to cardiovascular events, and may be related to chronic inflammation. We hypothesized that the anti-inflammatory benefits of higher dietary omega-3, compared to omega-6, poly-unsaturated fatty acids may modulate the inflammatory processes and reduce death risk. Study design Prospective cohort study using linear and Cox proportional regressions. Setting and Participants 145 hemodialysis patients from 8 DaVita dialysis clinics in Southern California during 2001-2007 Predictors Intake of dietary omega-3 and ratio of omega-6 to omega-3 using 3-day food record supplemented by dietary interview. Outcomes One-year change in serum C-reactive protein (CRP) and 6-year survival. Results Patients were 53±14 years old (mean±SD) and included 43% women and 42% African-Americans. Median (25th-75 percentile) of dietary omega-3 intake, ratio of omega-6 to omega-3 intake, baseline serum CRP, and change in CRP over one year were 1.1(0.8-1.6) g/day, 9.3(7.6-11.3), 3.1(0.8-6.8) mg/L, and +0.2(−0.4 to +0.8) mg/L, respectively. In regression models adjusted for case-mix, dietary calorie and fat intake, body mass index and history of hypertension, each 1-unit higher ratio of omega-6 to omega-3 intake was associated with 0.55 mg/L increase in serum CRP (p=0.03). In fully adjusted model, the death hazard ratios (95% confidence interval) for the 1st(1.7-<7.6) 2nd(7.6-<9.3), 3rd(9.3-<11.3) and 4th(11.3-17.4) quartiles of dietary omega-6 to omega-3 ratio were 0.39(0.14-1.18), 0.30(0.09-0.99), 0.67(0.25-1.79) and 1.00(reference), respectively (p-for-trend=0.06). Limitations Three-day food record may underestimate actual dietary fat intake at individual level. Conclusions Higher dietary omega-6 to omega-3 ratio appears associated with both worsening inflammation over time and a trend towards higher death risk in hemodialysis patients. Additional studies including interventional trials are needed to examine

  10. Long-Term Cold Acclimation Extends Survival Time at 0°C and Modifies the Metabolomic Profiles of the Larvae of the Fruit Fly Drosophila melanogaster

    PubMed Central

    Koštál, Vladimír; Korbelová, Jaroslava; Rozsypal, Jan; Zahradníčková, Helena; Cimlová, Jana; Tomčala, Aleš; Šimek, Petr

    2011-01-01

    Background Drosophila melanogaster is a chill-susceptible insect. Previous studies on this fly focused on acute direct chilling injury during cold shock and showed that lower lethal temperature (LLT, approximately −5°C) exhibits relatively low plasticity and that acclimations, both rapid cold hardening (RCH) and long-term cold acclimation, shift the LLT by only a few degrees at the maximum. Principal Findings We found that long-term cold acclimation considerably improved cold tolerance in fully grown third-instar larvae of D. melanogaster. A comparison of the larvae acclimated at constant 25°C with those acclimated at constant 15°C followed by constant 6°C for 2 d (15°C→6°C) showed that long-term cold acclimation extended the lethal time for 50% of the population (Lt50) during exposure to constant 0°C as much as 630-fold (from 0.137 h to 86.658 h). Such marked physiological plasticity in Lt50 (in contrast to LLT) suggested that chronic indirect chilling injury at 0°C differs from that caused by cold shock. Long-term cold acclimation modified the metabolomic profiles of the larvae. Accumulations of proline (up to 17.7 mM) and trehalose (up to 36.5 mM) were the two most prominent responses. In addition, restructuring of the glycerophospholipid composition of biological membranes was observed. The relative proportion of glycerophosphoethanolamines (especially those with linoleic acid at the sn-2 position) increased at the expense of glycerophosphocholines. Conclusion Third-instar larvae of D. melanogaster improved their cold tolerance in response to long-term cold acclimation and showed metabolic potential for the accumulation of proline and trehalose and for membrane restructuring. PMID:21957472

  11. Long-term survival after a favorable response to anti-EGFR antibody plus chemotherapy to treat bone marrow metastasis: a case report of KRAS-wildtype rectal cancer

    PubMed Central

    Nakamura, Sho; Fukui, Tadahisa; Suzuki, Shuhei; Takeda, Hiroyuki; Watanabe, Kaname; Yoshioka, Takashi

    2017-01-01

    Bone marrow metastasis is a rare consequence of colorectal cancer that results in a poor prognosis; few reports describe a favorable response to doublet chemotherapy combined with targeted therapy, which is currently the standard treatment. We experienced a case where anti-epidermal growth factor receptor (EGFR) antibody produced a marked anti-tumor response to bone marrow metastasis that led to long-term survival. A 51-year-old man was diagnosed with a primary KRAS-wildtype rectal cancer with multiple metastases, including the bone marrow. Disease control was achieved for 10.8 months following chemotherapy with a modified FOLFOX6 regimen combined with an anti-EGFR antibody. He died of cancer 22.7 and 16.6 months after disease onset and first-line chemotherapy, respectively. This case shows that early tumor shrinkage and deepness of response to the anti-EGFR antibody were observed even in a patient with bone marrow metastasis. Anti-EGFR antibody therapy should therefore be considered even when a patient’s medical condition appears to be poor owing to bone marrow metastasis. Moreover, tumors that are likely to be sensitive to chemotherapy, such as RAS-wildtype colorectal cancers, can be considered for anti-EGFR antibody therapy even if the patient is considered unfit for chemotherapy. PMID:28260928

  12. Induction Chemotherapy Improved Long-term Outcomes of Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: A Propensity Matched Analysis of 5-year Survival Outcomes in the Era of Intensity-modulated Radiotherapy

    PubMed Central

    Peng, Hao; Chen, Lei; Zhang, Jian; Li, Wen-Fei; Mao, Yan-Ping; Zhang, Yuan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2017-01-01

    Background: The aim of this study is to evaluate the long-term therapeutic gain of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT). Methods: Data on 957 patients with stage T1-2N2-3 or T3-4N1-3 NPC treated with IMRT were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance influence of various covariates. Patient survival between IC and non-IC groups were compared. Results: For the 318 pairs selected from the original 957 patients by PSM, the median follow-up duration was 57.13 months (range, 1.27-78.1 months). The 5-year overall survival (OS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and locoregional relapse-free survival (LRRFS) rates for IC group vs. non-IC group were 87.2% vs. 80.8% (P = 0.023), 88.1% vs. 83.2% (P = 0.071), 80.7% vs. 71.4% (P = 0.011) and 92.1% vs. 86.7% (P = 0.081), respectively. Multivariate analysis identify IC as an independent prognostic factor for OS (HR, 0.595; 95% CI, 0.397-0.891; P = 0.012) and DFS (HR, 0.627; 95% CI, 0.451-0.872; P = 0.006). After excluding the patients not receiving concurrent chemotherapy, IC was found to be an independent prognostic factor for OS (HR, 0.566; 95% CI, 0.368-0.872; P = 0.01), DMFS (HR, 0.580; 95% CI, 0.367-0.916; P = 0.02) and DFS (HR, 0.633; 95% CI, 0.444-0.903; P = 0.012). Conclusions: IC is an effective treatment modality for patients with stage T1-2N2-3 and T3-4N1-3 NPC, and the incorporation of IC with standard CCRT could achieve the best therapeutic gain. PMID:28261337

  13. Effectivity of a strategy in elderly AML patients to reach allogeneic stem cell transplantation using intensive chemotherapy: Long-term survival is dependent on complete remission after first induction therapy.

    PubMed

    von dem Borne, P A; de Wreede, L C; Halkes, C J M; Marijt, W A F; Falkenburg, J H F; Veelken, H

    2016-07-01

    Intensive chemotherapy followed by allogeneic stem cell transplantation (alloSCT) can cure AML. Most studies on alloSCT in elderly AML report results of highly selected patient cohorts. Hardly any data exist on the effectiveness of prospective strategies intended to bring as many patients as possible to transplant. Between 2006 and 2011 we implemented a treatment algorithm for all newly diagnosed AML patients aged 61-75 years, consisting of intensive chemotherapy cycles to induce complete remission, followed by alloSCT. 44 of 60 (73%) newly diagnosed elderly AML patients started with chemotherapy. By meticulously following our algorithm in almost all patients, we could induce complete remission (CR) in 66% of patients starting with chemotherapy, and transplant 32% of these patients in continuous CR. Main reasons for failure were early relapse (16%), early death (14%), primary refractory disease (9%), and patient or physician decision to stop treatment (16%). Patients in continuous CR after first induction benefit most with 36% long-term survival. Patients not in CR after first induction benefit less; although additional chemotherapy induces CR in 45% of these patients, only 23% are transplanted and no long-term survival is observed, mainly due to relapse. Long-term survival in the group of 44 patients is 9% (median 4.5 years after alloSCT). Considering that 27% of patients do not start with chemotherapy and 64% of patients starting with chemotherapy do not reach alloSCT, the reasons for failure presented here should be used as a guide to develop new treatment algorithms to improve long-term survival in elderly AML patients.

  14. Long-term maintenance combination chemotherapy with OPEC/MPEC (vincristine or methotrexate, prednisolone, etoposide and cyclophosphamide) or with daily oral etoposide and prednisolone can improve survival and quality of life in adult T-cell leukemia/lymphoma.

    PubMed

    Matsushita, K; Matsumoto, T; Ohtsubo, H; Fujiwara, H; Imamura, N; Hidaka, S; Kukita, T; Tei, C; Matsumoto, M; Arima, N

    1999-12-01

    Acute leukemia and lymphoma varieties of adult T-cell leukemia/lymphoma (ATL) usually carry a poor prognosis. While etoposide is generally useful for treating ATL, especially as a daily oral maintenance regimen, etoposide has not proven effective in severe types of ATL efficient in some patients. Of 87 ATL patients whom we have treated, 51 had acute leukemia, 22 lymphoma and 14 progressive chronic leukemia. Seventy-nine patients were treated with a long term maintenance combination protocol, OPEC/MPEC (weekly doses of vincristine, 0.7 mg/m2 or methotrexate, 14 mg/m2; prednisolone, 20 mg/m2; etoposide, 70 mg/m2 and cyclophosphamide, 200 mg/m2). The other 8 patients, 3 with acute leukemia, 2 with lymphoma and 3 with progressive chronic leukemia, were treated with daily oral administration of 25 mg of etoposide and 10 mg of prednisolone (DOEP). The dose administered was modified in individual cases to maintain the granulocyte count and reduce the number of ATL cells. Considering both protocols, a complete response and a partial response were achieved in 31.0% and 58.6% patients, respectively. Median survival times (MST) of all patients and, acute leukemia, lymphoma and progressive chronic leukemia types were 7.5, 6.7, 9.6 and 12.4 months, respectively. Respective MST of patients treated with OPEC/MPEC or DOEP protocols were 7.1 and 18.0 months. Relatively normal WBC counts, lower lactate dehydrogenase concentration and normal calcium concentration, limited numbers of anatomic sites involved, good performance status and good response to chemotherapy were significantly associated with long survival time. Drug toxicity was not apparent, and about half of patients were treated in an outpatient setting.

  15. Long-term survival in a patient with progressive multifocal leukoencephalopathy after therapy with rituximab, fludarabine and cyclophosphamide for chronic lymphocytic leukemia.

    PubMed

    Garrote, Heidys; de la Fuente, Adolfo; Oña, Raquel; Rodríguez, Inmaculada; Echevarría, Juan E; Sepúlveda, Juan M; García, Juan F

    2015-01-01

    A 50-year-old male with chronic lymphocytic leukemia (CLL) was treated with fludarabine, cyclophosphamide and rituximab, which produced a complete remission. Eight months after the last dose of rituximab he had visual disturbance, diminished muscular strength in the right arm and vesicular-papular lesions in the left ophthalmic branch region of the V cranial nerve. These were initially interpreted as herpes virus encephalopathy (HVE), but brain magnetic resonance imaging (MRI) showed evidence of demyelination consistent with progressive multifocal leukoencephalopathy (PML). Cerebrospinal fluid (CSF) analysis was negative for varicella zoster virus (VZV) and John Cunningham virus (JCV) DNA. The clinical suggestion of PML prompted us to perform a brain biopsy and to start treatment with mefloquine. In the brain biopsy, histopathological features of demyelination were described and the polymerase chain reaction (PCR) identified JCV, confirming the diagnosis of PML. Treatment with mefloquine (250 mg/week) and dexamethasone (4 mg/day) was started and maintained for 6 months. A year later there was an almost complete resolution of the MRI lesions and the patient achieved a stable clinical state with persisting motor impairment and severe epilepsy. The patient is alive 38 months after diagnosis of PML, which is the longest known survival to date.

  16. [A long-surviving case of gastric cancer with peritoneal metastasis (P3) responding to short-term high-dose chemotherapy and long-term immunotherapy].

    PubMed

    Kusama, M; Kimura, K; Suzuki, K; Fukaya, Y; Saitoh, S; Eiraku, H; Kawahara, S; Ueno, M; Kawaguchi, M

    1989-10-01

    A 37-year-old female was admitted to our hospital for further examination of epigastralgia. She was diagnosed as having multiple metastases due to advanced gastric cancer (Borrmann type 3). The operative findings showed bilateral ovarian (Krukenberg), Schnitzler and widespread peritoneal metastases involving the appendix (P3H0N2S2). She underwent total gastrectomy, splenectomy, bilateral oophorectomy, and appendectomy with CDDP (100 mg intraperitoneal administration). After operation, CDDP (50 mg/body, twice i.p. and once i.v.) and PSK (3.0 g/day) were administered. She has been followed in our outpatient department for 3 years without any recurrence. The findings suggest that combination therapy using short-term high-dose chemotherapy and long-term immunotherapy can be effective for such cases.

  17. Can resistant coral-Symbiodinium associations enable coral communities to survive climate change? A study of a site exposed to long-term hot water input.

    PubMed

    Keshavmurthy, Shashank; Meng, Pei-Jie; Wang, Jih-Terng; Kuo, Chao-Yang; Yang, Sung-Yin; Hsu, Chia-Min; Gan, Chai-Hsia; Dai, Chang-Feng; Chen, Chaolun Allen

    2014-01-01

    Climate change has led to a decline in the health of corals and coral reefs around the world. Studies have shown that, while some corals can cope with natural and anthropogenic stressors either through resistance mechanisms of coral hosts or through sustainable relationships with Symbiodinium clades or types, many coral species cannot. Here, we show that the corals present in a reef in southern Taiwan, and exposed to long-term elevated seawater temperatures due to the presence of a nuclear power plant outlet (NPP OL), are unique in terms of species and associated Symbiodinium types. At shallow depths (<3 m), eleven coral genera elsewhere in Kenting predominantly found with Symbiodinium types C1 and C3 (stress sensitive) were instead hosting Symbiodinium type D1a (stress tolerant) or a mixture of Symbiodinium type C1/C3/C21a/C15 and Symbiodinium type D1a. Of the 16 coral genera that dominate the local reefs, two that are apparently unable to associate with Symbiodinium type D1a are not present at NPP OL at depths of <3 m. Two other genera present at NPP OL and other locations host a specific type of Symbiodinium type C15. These data imply that coral assemblages may have the capacity to maintain their presence at the generic level against long-term disturbances such as elevated seawater temperatures by acclimatization through successful association with a stress-tolerant Symbiodinium over time. However, at the community level it comes at the cost of some coral genera being lost, suggesting that species unable to associate with a stress-tolerant Symbiodinium are likely to become extinct locally and unfavorable shifts in coral communities are likely to occur under the impact of climate change.

  18. Population regulation in a changing environment: Long-term changes in growth, condition and survival of sprat, Sprattus sprattus L. in the Bristol Channel, UK

    NASA Astrophysics Data System (ADS)

    Henderson, Peter A.; Henderson, Rowena C.

    2017-02-01

    Sprat, Sprattus sprattus, is the dominant pelagic species in British inshore and estuarine waters. Within the Bristol Channel the population is almost totally composed of fish < 3 years old with the adults overwintering in Bridgwater Bay. Sprat follow regular seasonal migrations and occasionally form huge aggregations which together generate considerable between sample variability. Using a 36-year monthly time series collected in the Bristol Channel since 1980, together with two periods of intensive daily and weekly sampling, sprat growth is shown to have declined almost linearly over the last 36 years coincident with increasing late summer-autumn seawater temperatures. Longevity has also declined, with age 3 + sprat > 140 mm standard length lost to the population by 1999. Further, adult condition, measured as the average weight of a 103 mm standard length adult, declined rapidly from 13.7 g in 2007 to 9 g in 2011. Despite these changes, which would have reduced age-specific fecundity, a sign-rank test showed abundance of adult sprat has shown no long-term trend and Bulmer's test indicates density-dependent regulation is operating. While sprat recruitment is shown to be responding to the sunspot cycle, the North Atlantic Oscillation and sea water temperature, the impact of these variables on adult population density is damped because of density-dependent regulation. The result is that sprat respond to environmental change with large changes in their growth and condition, but the adult abundance is constrained and shows no long-term trend. Recruitment was modelled by combining a Ricker curve with terms for the response of sprat to solar activity, the North Atlantic Oscillation and spring temperature. It is shown that the stock-recruitment relationship does not form a simple curve, but is bounded within a region in which the upper and lower constraints are defined by environmental conditions. Within this bounded region the population trajectory under differing

  19. Long-term effect of the North Carolina graduated driver licensing system on licensed driver crash incidence: a 5-year survival analysis.

    PubMed

    Masten, Scott V; Foss, Robert D

    2010-11-01

    Several studies document the success of graduated driver licensing (GDL) systems in reducing young teen crash rates, but it is not yet clear whether any portion of the crash reduction is achieved by producing more capable drivers. The purpose of this study was to determine whether young teen drivers licensed under the North Carolina GDL system remain crash-free longer than those licensed prior to GDL, independent of the crude reductions in exposure (i.e., decreasing and delaying licensure) that may be responsible for most documented effects of GDL. Survival analysis was used to compare retrospective cohorts of 16-17 year olds before (n=105,569) and after (n=327,054) the North Carolina GDL system was implemented. The crash incidence of GDL-licensed 16-17 year olds (combined) was 10% lower than that for pre-GDL teens for at least 5 years after being licensed to drive independently (hazard ratio [HR]=0.90; 95% confidence interval [CI]=0.89, 0.91). However, more refined analysis revealed the reductions to only be among females (7%; HR=0.93; CI=0.91, 0.94) and males (15%; HR=0.85, CI=0.84, 0.87) licensed at age 16 and not among females (0%; HR=1.00; CI=0.95, 1.06) and males (0%; HR=1.00; CI=0.92, 1.09) licensed at age 17. Sixteen-year-old drivers licensed under the North Carolina GDL system experienced lower first-crash incidence during the first 5 years of unsupervised driving than did those licensed under the previous system. The benefits are greater for males, who tend to have higher crash rates. The findings contradict conventional wisdom that the entire benefit of GDL results merely from decreasing or delaying licensure among young drivers.

  20. Long-term survival for 93 months of limited-stage small cell lung cancer: A case report and literature review

    PubMed Central

    Zhong, Yujie; Zhang, Qiuhong; Deng, Wenjing; Zhang, Yuping; Ming, Zongjuan; Hou, Yanli; Niu, Zequn; Yang, Shuanying

    2014-01-01

    A 49-year-old man was diagnosed with small cell lung cancer in May 2005. Chemotherapy was started with 60 mg/day cisplatin iv drip (from days one to three), 2 mg topotecan (TP) hydrochloride iv drip (from days one to four), and traditional Chinese medicine (TCM) AiDi injection for anti-tumor. After four cycles, he underwent conformal radiotherapy with 56Gy/28 fractions in October 2005. In April 2006, a mass on the right supraclavicular area was found. Therefore, he underwent another course of radiotherapy. The fields included the right supraclavicular area and the radiation dose was 50Gy/25 fractions. After completion of chemoradiotherapy, the patient achieved complete remission. Subsequently, the patient received prophylactic cranial irradiation (PCI). Until April of 2012, he had been followed up regularly. Since the SCLC diagnosis, he had received TCM for seven years. In April 2012, the patient complained of coughing again. Subsequently, the patient was given five cycles of an etoposide carboplatin regimen. A computed tomography (CT) scan was performed for review, which showed no obvious change. The patient underwent a second-line chemotherapy irinotecan cisplatin three times. However, the symptoms and CT of this patient showed no significant improvement. We changed the chemotherapy regimen to TP (topotecan 1.2 mg iv drip, days one to five; carboplatin 100 mg iv drip, days one to five). After two TP regimens, the patient died in his sleep on 3 March 2013. In this case, the standardized sequential chemotherapy and radiotherapy treatment, PCI, TCM, and good compliance may have contributed to the patient's longer survival. PMID:26767023

  1. Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft.

    PubMed

    Mohiuddin, Muhammad M; Singh, Avneesh K; Corcoran, Philip C; Thomas, Marvin L; Clark, Tannia; Lewis, Billeta G; Hoyt, Robert F; Eckhaus, Michael; Pierson, Richard N; Belli, Aaron J; Wolf, Eckhard; Klymiuk, Nikolai; Phelps, Carol; Reimann, Keith A; Ayares, David; Horvath, Keith A

    2016-04-05

    Preventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46.hTBM), that were transplanted into baboons. Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and αCD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed αCD40 (2C10R4) antibody. Median (298 days) and longest (945 days) graft survival in five consecutive recipients using this regimen is significantly prolonged over our recently established survival benchmarks (180 and 500 days, respectively). Remarkably, the reduction of αCD40 antibody dose on day 100 or after 1 year resulted in recrudescence of anti-pig antibody and graft failure. In conclusion, genetic modifications (GTKO.hCD46.hTBM) combined with the treatment regimen tested here consistently prevent humoral rejection and systemic coagulation pathway dysregulation, sustaining long-term cardiac xenograft survival beyond 900 days.

  2. Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft

    PubMed Central

    Mohiuddin, Muhammad M.; Singh, Avneesh K.; Corcoran, Philip C.; Thomas III, Marvin L.; Clark, Tannia; Lewis, Billeta G.; Hoyt, Robert F.; Eckhaus, Michael; Pierson III, Richard N.; Belli, Aaron J.; Wolf, Eckhard; Klymiuk, Nikolai; Phelps, Carol; Reimann, Keith A.; Ayares, David; Horvath, Keith A.

    2016-01-01

    Preventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46.hTBM), that were transplanted into baboons. Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and αCD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed αCD40 (2C10R4) antibody. Median (298 days) and longest (945 days) graft survival in five consecutive recipients using this regimen is significantly prolonged over our recently established survival benchmarks (180 and 500 days, respectively). Remarkably, the reduction of αCD40 antibody dose on day 100 or after 1 year resulted in recrudescence of anti-pig antibody and graft failure. In conclusion, genetic modifications (GTKO.hCD46.hTBM) combined with the treatment regimen tested here consistently prevent humoral rejection and systemic coagulation pathway dysregulation, sustaining long-term cardiac xenograft survival beyond 900 days. PMID:27045379

  3. Long-term results after robotically assisted coronary bypass surgery

    PubMed Central

    Ramahi, Jehad; Hasan, Faisal; Edris, Ahmad; Bartel, Thomas; Nair, Ravi; Tuzcu, Murat; Suri, Rakesh; Mihaljevic, Tomislav

    2016-01-01

    Background Robotically-assisted coronary bypass grafting (CABG) was introduced in 1998 and dedicated centers have continuously applied and developed this minimally invasive method of coronary bypass surgery. While short-term results are relatively well published, data on long-term outcome are limited. In this literature review, we assessed the outcomes after robotic CABG following the first postoperative year. Methods We searched PubMed for articles containing the terms “robotic” or “robotically assisted” and “coronary bypass”. A total of 11 papers contained long-term results. We specifically investigated survival, graft patency, freedom from angina and re-intervention, as well as freedom from major adverse cardiac and cerebrovascular events (MACCE). Results Five-year survival after robotic CABG was consistently consistently greater than 90% and graft patency between 3 and 5 years was reported to be above 90%. Fifteen percent to 26% of patients re-experienced angina at 3 to 5 years postoperatively. Long-term freedom from re-intervention reached the range and the 5-year freedom from MACCE rate was approximately 75%. Conclusions According to data in the literature, long-term results after CABG carried out with the assistance of a surgical robot appear to be in line with results achieved after conventional CABG. PMID:27942487

  4. Long Term Progression-Free Survival in a Patient with Locally Advanced Prostate Cancer under Low Dose Intermittent Androgen Deprivation Therapy with Bicalutamide Only.

    PubMed

    Latz, Stefan; Fisang, Christian; Ebert, Wolfram; Orth, Stefan; Engehausen, Dirk G; Müller, Stefan C; Anding, Ralf

    2015-01-01

    Androgen deprivation is a common treatment option in patients with locally advanced or metastatic prostate cancer. No case of long term treatment with an intermittent approach with only low dose bicalutamide (50 mg daily) has been described yet. We report a 60-year-old patient, initially presenting with a PSA elevation of 19.2 ng/mL in 1996. After diagnosis of well to moderately differentiated prostate cancer by transrectal biopsy, the patient underwent an open radical prostatectomy. Final diagnosis was adenocarcinoma of the prostate, classified as pT3a, pR1, pV0, and pL1. Adjuvant intermittent androgen deprivation therapy with flutamide 250 mg was applied, which was changed to bicalutamide 50 mg once daily when it became available in 2001. Six on-phases were performed and PSA values never exceeded 20 ng/mL. The patient did not experience any serious side effects. To date, there are no clinical or radiological signs of progression. Current PSA value is 3.5 ng/mL.

  5. WWC Review of the Report "Staying on Track: Testing Higher Achievement's Long-Term Impact on Academic Outcomes and High School Choice." What Works Clearinghouse Single Study Review

    ERIC Educational Resources Information Center

    What Works Clearinghouse, 2014

    2014-01-01

    This study of 952 fifth and sixth graders in Washington, DC, and Alexandria, Virginia, found that students who were offered the "Higher Achievement" program had higher test scores in mathematical problem solving and were more likely to be admitted to and attend private competitive high schools. "Higher Achievement" is a…

  6. Effect of chilling temperature on the long-term survival of rabbit spermatozoa held either in a tris-based or a jellified extender.

    PubMed

    Rosato, Mp; Iaffaldano, N

    2011-04-01

    As the preservation of the fertilizing capacity of rabbit spermatozoa for several days after semen collection remains a major target for the artificial insemination programs of rabbit breeding, a study was conducted to compare the efficacy of 5 or 15°C as holding temperature in lengthening the preservability of rabbit semen quality during 192 h of storage both in a solid (Cunigel) and a liquid (Tris-Citric acid-Glucose; TCG) extender. Six pooled semen samples (two ejaculates/male; two-three males/pool) were taken and made four aliquots: two aliquots were tenfold diluted with the TCG extender, whereas the other two were tenfold diluted with the Cunigel extender. One aliquot per diluent was stored at 5°C and the second one at 15°C. Sperm motility (light microscope), viability (SyBr-PI staining), plasma membrane functional integrity (Hypo-osmotic swelling test) and acrosome integrity (PSA-FITC staining) were recorded at 0, 48, 120 and 192 h of storage. In liquid-stored spermatozoa, mass motility and viability were significantly higher (p ≤ 0.05) in samples stored at 5°C than at 15°C at all the storage times; at 5°C resulted also higher (p ≤ 0.05) the percentages of both forward motility at 48 h and sperm functional integrity at 120 and 192 h of storage, whereas chilling temperature did not affect acrosome integrity. With the Cunigel extender, all the semen qualitative parameters were significantly higher in sample stored at 5 than 15°C over storage time (p ≤ 0.05); only acrosome integrity at 192 h was not different according to the chilling temperatures. In conclusion, 5°C were better than 15°C for the long-term storage of rabbit semen both in the TCG and Cunigel extender.

  7. Medical Status of 219 Children with Biliary Atresia Surviving Long-Term with their Native Livers: Results from a North American Multicenter Consortium

    PubMed Central

    Ng, Vicky Lee; Haber, Barbara H.; Magee, John C.; Miethke, Alexander; Murray, Karen F.; Michail, Sonia; Karpen, Saul J.; Kerkar, Nanda; Molleston, JeanP.; Romero, Rene; Rosenthal, Philip; Schwarz, Kathleen B.; Shneider, Benjamin L.; P.Turmelle, Yumirle; Alonso, Estella M.; Sherker, Averell H.; Sokol, Ronald J.

    2014-01-01

    Objectives To examine the medical status of children with biliary atresia (BA) with their native livers after hepatic portoenterostomy (HPE) surgery. Study design The Childhood Liver Disease Research and Education Network (ChiLDREN) database was utilized to examine subjects with BA living with their native livers 5 or more years after HPE and to describe the prevalence of subjects with BA with an “ideal” outcome, defined as no clinical evidence of chronic liver disease, normal liver biochemical indices (aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase, platelet count, total bilirubin, International Normalized Ratio, and albumin) and normal Health-Related Quality of Life (HRQOL) 5 or more years after HPE. Results Children with BA (n=219; 43% male) with median age 9.7 years were studied. Median age at HPE was 56 (range 7-125) days. Median age- and sex-adjusted height and weight Z-scores at 5 year follow-up were 0.487 (interquartile range [IQR]: -0.27 to 1.02) and 0.00 (IQR: -0.74 to 0.70), respectively. During the 12 preceding months, cholangitis and bone fractures occurred in 17% and 5.5%, respectively. HRQOL was reported normal by 53% of patients. However, only 1.8% met the study definition of “ideal” outcome. Individual tests of liver synthetic function (TB, Alb, and INR) were normal in 75%, 85% and 73% of the study cohort. Conclusion Cholangitis and fractures in long-term survivors underscore the importance of ongoing medical surveillance. Over 98% of this North American cohort of subjects with BA living with native livers 5 or more years after HPE have clinical or biochemical evidence of chronic liver disease. PMID:25015575

  8. Nomogram for preoperative estimation of long-term survival of patients who underwent curative resection with hepatocellular carcinoma beyond Barcelona clinic liver cancer stage A1

    PubMed Central

    Zhao, Hui; Wu, Dong-Hao; Chen, Jie; Dong, Min; Lin, Qu; Wu, Xiang-Yuan; Li, Yang

    2016-01-01

    Background and Aims This retrospective cohort study developed a prognostic nomogram to predict the survival of hepatocellular carcinoma (HCC) patients diagnosed as beyond Barcelona clinic liver cancer stage A1 after resection and evaluated the possibility of using the nomogram as a treatment algorithm reference. Results The predictors included in the nomogram were total tumour volume, Child-Turcotte-Pugh class, plasma fibrinogen and portal vein tumour thrombus. Patients diagnosed as beyond A1 were stratified into low-, medium- and high-risk groups using nomogram scores of 0 and 51 with the total points of 225. Patients within A1 exhibited similar recurrence-free survival (RFS) and overall survival (OS) rates compared with the low-risk group. Patients in the medium-risk group exhibited a similar OS but a worse RFS rates compared with patients within A1. The high-risk group was associated with worse RFS and OS rates compared with the patients within A1 (3-year RFS rates, 27.0% vs. 60.3%, P < 0.001; 3-year OS rates, 49.2% vs. 83.1%, P < 0.001). Methods A total of 352 HCC patients undergoing curative resection from September 2003 to December 2012 were included to develop a nomogram to predict overall survival after resection. Univariate and multivariate survival analysis were used to identify prognostic factors. A visually orientated nomogram was constructed using a Cox proportional hazards model. Conclusions This user-friendly nomogram offers an individualized preoperative recurrence risk estimation and stratification for HCC patients beyond A1 undergoing resection. Resection should be considered the first-line treatment for low-risk patients. PMID:27542216

  9. Nitrite survival and nitrous oxide production of denitrifying phosphorus removal sludges in long-term nitrite/nitrate-fed sequencing batch reactors.

    PubMed

    Wang, Yayi; Zhou, Shuai; Ye, Liu; Wang, Hong; Stephenson, Tom; Jiang, Xuxin

    2014-12-15

    Nitrite-based phosphorus (P) removal could be useful for innovative biological P removal systems where energy and carbon savings are a priority. However, using nitrite for denitrification may cause nitrous oxide (N2O) accumulation and emissions. A denitrifying nitrite-fed P removal system [Formula: see text] was successfully set up in a sequencing batch reactor (SBR) and was run for 210 days. The maximum pulse addition of nitrite to [Formula: see text] was 11 mg NO2(-)-N/L in the bulk, and a total of 34 mg NO2(-)-N/L of nitrite was added over three additions. Fluorescent in situ hybridization results indicated that the P-accumulating organisms (PAOs) abundance was 75 ± 1.1% in [Formula: see text] , approximately 13.6% higher than that in a parallel P removal SBR using nitrate [Formula: see text] . Type II Accumulibacter (PAOII) (unable to use nitrate as an electron acceptor) was the main PAOs species in [Formula: see text] , contributing 72% to total PAOs. Compared with [Formula: see text] , [Formula: see text] biomass had enhanced nitrite/free nitrous acid (FNA) endurance, as demonstrated by its higher nitrite denitrification and P uptake rates. N2O accumulated temporarily in [Formula: see text] after each pulse of nitrite. Peak N2O concentrations in the bulk for [Formula: see text] were generally 6-11 times higher than that in [Formula: see text] ; these accumulations were rapidly denitrified to nitrogen gases. N2O concentration increased rapidly in nitrate-cultivated biomass when 5 or 10 mg NO2(-)-N/L per pulse was added. Whereas, N2O accumulation did not occur in nitrite-cultivated biomass until up to 30 mg NO2(-)-N/L per pulse was added. Long-term acclimation to nitrite and pulse addition of nitrite in [Formula: see text] reduced the risk of nitrite accumulation, and mitigated N2O accumulation and emissions from denitrifying P removal by nitrite.

  10. Long-term outcomes after severe shock.

    PubMed

    Pratt, Cristina M; Hirshberg, Eliotte L; Jones, Jason P; Kuttler, Kathryn G; Lanspa, Michael J; Wilson, Emily L; Hopkins, Ramona O; Brown, Samuel M

    2015-02-01

    Severe shock is a life-threatening condition with very high short-term mortality. Whether the long-term outcomes among survivors of severe shock are similar to long-term outcomes of other critical illness survivors is unknown. We therefore sought to assess long-term survival and functional outcomes among 90-day survivors of severe shock and determine whether clinical predictors were associated with outcomes. Seventy-six patients who were alive 90 days after severe shock (received ≥1 μg/kg per minute of norepinephrine equivalent) were eligible for the study. We measured 3-year survival and long-term functional outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, and an employment instrument. We also assessed the relationship between in-hospital predictors and long-term outcomes. The mean long-term survival was 5.1 years; 82% (62 of 76) of patients survived, of whom 49 were eligible for follow-up. Patients who died were older than patients who survived. Thirty-six patients completed a telephone interview a mean of 5 years after hospital admission. The patients' Physical Functioning scores were below U.S. population norms (P < 0.001), whereas mental health scores were similar to population norms. Nineteen percent of the patients had symptoms of depression, 39% had symptoms of anxiety, and 8% had symptoms of posttraumatic stress disorder. Thirty-six percent were disabled, and 17% were working full-time. Early survivors of severe shock had a high 3-year survival rate. Patients' long-term physical and psychological outcomes were similar to those reported for cohorts of less severely ill intensive care unit survivors. Anxiety and depression were relatively common, but only a few patients had symptoms of posttraumatic stress disorder. This study supports the observation that acute illness severity does not determine long-term outcomes. Even extremely

  11. Radiation Use and Long-Term Survival in Breast Cancer Patients With T1, T2 Primary Tumors and One to Three Positive Axillary Lymph Nodes

    SciTech Connect

    Buchholz, Thomas A. Woodward, Wendy A.; Duan Zhigang; Fang Shenying; Oh, Julia L.; Tereffe, Welela; Strom, Eric A.; Perkins, George H.; Yu, T.-K.; Hunt, Kelly K.; Meric-Bernstam, Funda; Hortobagyi, Gabriel N.; Giordano, Sharon H.

    2008-07-15

    Background: For patients with Stage II breast cancer with one to three positive lymph nodes, controversy exists about whether radiation as a component of treatment provides a survival benefit. Methods and Materials: We analyzed data from patients with Stage II breast cancer with one to three positive lymph nodes diagnosed from 1988-2002 in the Surveillance, Epidemiology, and End Results registry and compared the outcome of 12,693 patients treated with breast-conservation therapy with radiation (BCT + XRT) with the 18,902 patients treated with mastectomy without radiation (MRM w/o XRT). Results: Patients treated with BCT + XRT were younger, were more likely to be treated in recent years of the study period, more commonly had T1 primary tumors, and had fewer involved nodes compared with those treated with MRM w/o XRT (p < 0.001 for all differences). The 15-year breast cancer-specific survival rate for the BCT + XRT group was 80% vs. 72% for the MRM w/o XRT group (p < 0.001). Cox regression analysis showed that MRM w/o XRT was associated with a hazard ratio for breast cancer death of 1.19 (p < 0.001) and for overall death of 1.25 (p < 0.001). The survival benefit in the BCT + XRT group was not limited to subgroups with high-risk disease features. Conclusions: Radiation use was independently associated with improved survival for patients with Stage II breast cancer with one to three positive lymph nodes. Because multivariate analyses of retrospective data cannot account for all potential biases, these data require confirmation in randomized clinical trials.

  12. Decreased survival of glioma patients with astrocytoma grade IV (glioblastoma multiforme) associated with long-term use of mobile and cordless phones.

    PubMed

    Carlberg, Michael; Hardell, Lennart

    2014-10-16

    On 31 May 2011 the WHO International Agency for Research on Cancer (IARC) categorised radiofrequency electromagnetic fields (RF-EMFs) from mobile phones, and from other devices that emit similar non-ionising electromagnetic fields, as a Group 2B, i.e., a "possible", human carcinogen. A causal association would be strengthened if it could be shown that the use of wireless phones has an impact on the survival of glioma patients. We analysed survival of 1678 glioma patients in our 1997-2003 and 2007-2009 case-control studies. Use of wireless phones in the >20 years latency group (time since first use) yielded an increased hazard ratio (HR) = 1.7, 95% confidence interval (CI) = 1.2-2.3 for glioma. For astrocytoma grade IV (glioblastoma multiforme; n = 926) mobile phone use yielded HR = 2.0, 95% CI = 1.4-2.9 and cordless phone use HR = 3.4, 95% CI = 1.04-11 in the same latency category. The hazard ratio for astrocytoma grade IV increased statistically significant per year of latency for wireless phones, HR = 1.020, 95% CI = 1.007-1.033, but not per 100 h cumulative use, HR = 1.002, 95% CI = 0.999-1.005. HR was not statistically significant increased for other types of glioma. Due to the relationship with survival the classification of IARC is strengthened and RF-EMF should be regarded as human carcinogen requiring urgent revision of current exposure guidelines.

  13. Diagnosis of second primary tumor and long-term survival after single initial triple endoscopy in patients with head and neck cancer.

    PubMed

    Priante, Antonio Vitor Martins; Gross, Jefferson Luiz; Sztokfisz, Claudia Zitron; Nishimoto, Inês Nobuko; Kowalski, Luiz Paulo

    2014-08-01

    Patients with squamous cell carcinoma of the upper aerodigestive tract (UADT) have a high risk of developing second primary tumors (SPTs). Most of the studies concerning triple endoscopy (laryngoscopy, digestive tract endoscopy and bronchoscopy) describe the frequency and stage of the SPT, but not its impact on survival. This study is a matched pair analysis that included patients with squamous cell carcinoma of the UADT who were subjected to a triple endoscopy before the first treatment, matched with patients who did not undergo triple endoscopy. One hundred and thirty-five patients were included in each group. The diagnosis of an SPT was more frequent in the initial triple endoscopy group than in the control group (34 and 20 cases, respectively). In the initial triple endoscopy group, 50.0 % of these tumors were diagnosed simultaneously, whereas in the control, only 5.0 %. No significant differences in the survival rates or in clinical stage of the SPTs were found in the two groups. There was no difference in the clinical stage of the SPT and the survival rates of the patient groups who underwent triple endoscopy at the initial evaluation and those subjected to only a routine evaluation and follow-up.

  14. Impact of different cryoprotectants on the survival of freeze-dried Lactobacillus rhamnosus and Lactobacillus casei/paracasei during long-term storage.

    PubMed

    Jofré, A; Aymerich, T; Garriga, M

    2015-01-01

    The production of long shelf-life highly concentrated dried probiotic/starter cultures is of paramount importance for the food industry. The aim of the present study was to evaluate the protective effect of glucose, lactose, trehalose, and skim milk applied alone or combined upon the survival of potentially probiotic Lactobacillus rhamnosus CTC1679, Lactobacillus casei/paracasei CTC1677 and L. casei/paracasei CTC1678 during freeze-drying and after 39 weeks of storage at 4 and 22 °C. Immediately after freeze-drying, the percentage of survivors was very high (≥ 94%) and only slight differences were observed among strains and cryoprotectants. In contrast, during storage, survival in the dried state depended on the cryoprotectant, temperature and strain. For all the protectants assayed, the stability of the cultures was remarkably higher when stored under refrigeration (4 °C). Under these conditions, skim milk alone or supplemented with trehalose or lactose showed the best performance (reductions ≤ 0.9 log units after 39 weeks of storage). The lowest survival was observed during non-refrigerated storage and with glucose and glucose plus milk; no viable cells left at the end of the storage period. Thus, freeze-drying in the presence of appropriate cryoprotectants allows the production of long shelf-life highly concentrated dried cultures ready for incorporation in high numbers into food products as starter/potential probiotic cultures.

  15. Long Term Outcomes after Pediatric Liver Transplantation

    PubMed Central

    2013-01-01

    Long term outcomes after liver transplantation are major determinants of quality of life and of the value of this heroic treatment. As short term outcomes are excellent, our community is turning to take a harder look at long term outcomes. The purpose of this paper is to review these outcomes, and highlight proposed treatments, as well as pressing topics needing to be studied. A systemic review of the English literature was carried in PubMed, covering all papers addressing long term outcomes in pediatric liver transplant from 2000-2013. Late outcomes after pediatric liver transplant affect the liver graft in the form of chronic liver dysfunction. The causes include rejection particularly humoral rejection, but also de novo autoimmune hepatitis, and recurrent disease. The metabolic syndrome is a major factor in long term cardiovascular complication risk. Secondary infections, kidney dysfunction and malignancy remain a reality of those patients. There is growing evidence of late cognitive and executive function delays affecting daily life productivity as well as likely adherence. Finally, despite a good health status, quality of life measures are comparable to those of children with chronic diseases. Long term outcomes are the new frontier in pediatric liver transplantation. Much is needed to improve graft survival, but also to avoid systemic morbidities from long term immunosuppression. Quality of life is a new inclusive measure that will require interventions and innovative approaches respectful not only on the patients but also of their social circle. PMID:24511516

  16. Long term survival with stereotactic ablative radiotherapy (SABR) versus thoracoscopic sublobar lung resection in elderly people: national population based study with propensity matched comparative analysis

    PubMed Central

    Paul, Subroto; Lee, Paul C; Mao, Jialin; Isaacs, Abby J

    2016-01-01

    Objectives To compare cancer specific survival after thoracoscopic sublobar lung resection and stereotactic ablative radiotherapy (SABR) for tumors ≤2 cm in size and thoracoscopic resection (sublobar resection or lobectomy) and SABR for tumors ≤5 cm in size. Design National population based retrospective cohort study with propensity matched comparative analysis. Setting Surveillance, Epidemiology, and End Results (SEER) registry linked with Medicare database in the United States. Participants Patients aged ≥66 with lung cancer undergoing SABR or thoracoscopic lobectomy or sublobar resection from 1 Oct 2007 to 31 June 2012 and followed up to 31 December 2013. Main outcome measures Cancer specific survival after SABR or thoracoscopic surgery for lung cancer. Results 690 (275 (39.9%) SABR and 415 (60.1%) thoracoscopic sublobar lung resection) and 2967 (714 (24.1%) SABR and 2253 (75.9%) thoracoscopic resection) patients were included in primary and secondary analyses. The average age of the entire cohort was 76. Follow-up of the entire cohort ranged from 0 to 6.25 years, with an average of three years. In the primary analysis of patients with tumors sized ≤2 cm, 37 (13.5%) undergoing SABR and 44 (10.6%) undergoing thoracoscopic sublobar resection died from lung cancer, respectively. The cancer specific survival diverged after one year, but in the matched analysis (201 matched patients in each group) there was no significant difference between the groups (SABR v sublobar lung resection mortality: hazard ratio 1.32, 95% confidence interval 0.77 to 2.26; P=0.32). Estimated cancer specific survival at three years after SABR and thoracoscopic sublobar lung resection was 82.6% and 86.4%, respectively. The secondary analysis (643 matched patients in each group) showed that thoracoscopic resection was associated with improved cancer specific survival over SABR in patients with tumors sized ≤5 cm (SABR v resection mortality: hazard ratio 2.10, 1.52 to 2.89; P<0

  17. T-cell-depleted allogeneic transplant without donor leukocyte infusions results in excellent long-term survival in patients with multiply relapsed Lymphoma. Predictors for survival after transplant relapse

    PubMed Central

    KENKRE, VAISHALEE P.; HOROWITZ, SARAH; ARTZ, ANDREW S.; LIAO, CHUANHONG; COHEN, KENNETH S.; GODLEY, LUCY A.; KLINE, JUSTIN P.; SMITH, SONALI M.; STOCK, WENDY; VAN BESIEN, KOEN

    2013-01-01

    We analyzed 67 patients with lymphoma who received alemtuzumab-based conditioning regimens for allogeneic stem cell transplant and no post-transplant DLI. The median age was 54 (24–70), 43% had unrelated donors, 34% had chemotherapy refractory disease, and 25% had an elevated LDH. With a median follow-up for survivors of 35 months, the estimated 3-year progression-free survival (PFS) and overall survival (OS) were 30% and 47%, respectively. Chemosensitivity by CT and pre-transplant LDH were independent prognostic factors for both overall survival and progression-free survival. Patient age, performance status, donor type, lymphoma subtype, disease sensitivity by PET, and conditioning regimen did not correlate with PFS and OS. Patients who relapsed greater than 6 months after allogeneic transplant were frequently able to re-enter a subsequent durable remission. Our experience confirms the curative potential of alemtuzumab-containing RIC regimens for allogeneic HCT in patients with relapsed lymphoma without prophylactic DLI. An elevated pre-transplant LDH and chemorefractory disease prior to transplant confer a worse prognosis, while PET scan findings do not have this same implication. Patients who relapse greater than 6 months after their transplant are likely to achieve a subsequent remission with any of a variety of interventions, suggesting that GVL effects can be operative even after recurrence. Our outcomes challenge the utility of the common practice of prophylactic DLI after T-depleted transplant for lymphoma. PMID:21142785

  18. Long-term survival of New Zealand rabbit haemorrhagic disease virus RNA in wild rabbits, revealed by RT-PCR and phylogenetic analysis.

    PubMed

    Forrester, N L; Boag, B; Moss, S R; Turner, S L; Trout, R C; White, P J; Hudson, P J; Gould, E A

    2003-11-01

    Because Rabbit haemorrhagic disease virus (RHDV) is highly pathogenic for rabbits, farmers illegally introduced it as a bio-control agent onto New Zealand farms in 1997. The virus was dispersed rapidly, initially causing high fatality rates in rabbits. Nevertheless, many survived and these surviving rabbits have been investigated for evidence of infection by RHDV. Livers from healthy rabbits contained RHDV-specific RNA, as shown by nested RT-PCR sequencing. The sequences of the viral capsids were related closely to the released Czech strain of RHDV, although the sequence from one rabbit was related most closely to a Spanish strain of RHDV. Phylogenetic analysis of the capsid sequences of 38 samples implied that there have been at least two introductions of the Czech virus into New Zealand, probably corresponding firstly to the original illegal introduction by farmers and secondly to the introduction of the same virus under governmental control. Genomic length sequence of two samples was obtained, suggesting that they may have retained the potential to be infectious, although this has not yet been demonstrated. The detection of genomic-length RNA in the liver of healthy rabbits suggests that even though a highly virulent virus was introduced into New Zealand, it rapidly established persistent or latent infections in a proportion of rabbits. This might account for their ability to survive in the face of virulent released virus. Moreover, the co-circulation of other strains of RHDV in the same rabbit population, such as the Spanish strain, might also impact on their susceptibility to the bio-control agent.

  19. Cumulative score based on preoperative plasma fibrinogen and serum C-reactive protein could predict long-term survival for esophageal squamous cell carcinoma

    PubMed Central

    Zhang, Fei; Sun, Peng; Wu, Ai-Ran; Zhang, Min; Jiang, Yu-Lu; Wu, Jing; Lu, Yan-Hong; Xu, Qiu-Yan; Zhan, Xiao-Hong; Zhang, Rong-Xin; Qian, Li-Ting; He, Jie

    2016-01-01

    The present study was to establish a prognostic indicator based on preoperative fibrinogen and C-reactive protein (CRP) (FC score) in esophageal squamous cell carcinoma (ESCC). Clinicopathologic characteristics, preoperative plasma fibrinogen and serum CRP levels were reviewed in patients who underwent transthoracic esophagectomy. The optimal cut-off value for fibrinogen and CRP was defined as 4.0 g/dL and 10.0 mg/L according to previous reports. Patients with elevated fibrinogen and CRP levels were assigned a score of 2, those with only one of these two abnormalities were allocated a score of 1, and those with neither of the two abnormalities were assigned a score of 0. Preoperative FC score was significantly correlated with degree of differentiation, depth of invasion, tumor-node-metastasis (TNM) stage and modified Glasgow Prognostic Score (mGPS). No significant differences in age, gender, tumor length, tumor location, lymph node status or smoking were identified between groups. Univariate survival analysis demonstrated that high preoperative FC score (1/2) was significantly associated with impaired disease free survival (DFS) [hazard ratio (HR), 1.650; 95% confidence interval (CI), 1.181-2.303; P = 0.003] and overall survival (OS) (HR, 1.879; 95% CI, 1.333-2.648; P<0.001), and it remained an independent predictor for both DFS (HR, 1.468; 95% CI, 1.043-2.067; P=0.028) and OS (HR, 2.070; 95% CI, 1.266-3.385; P=0.004) in multivariate Cox regression analysis. Preoperative FC score might represent a new potential marker of worst prognosis that warrants further evaluation in prospective and large cohort studies among ESCC patients who underwent transthoracic esophagectomy. PMID:27517497

  20. ‘Default’ generated neonatal regulatory T cells are hypomethylated at conserved non-coding sequence 2 and promote long-term cardiac allograft survival

    PubMed Central

    Cheng, Chao; Wang, Sihua; Ye, Ping; Huang, Xiaofan; Liu, Zheng; Wu, Jie; Sun, Yuan; Xie, Aini; Wang, Guohua; Xia, Jiahong

    2014-01-01

    Regulatory T (Treg) cells play an important role in the maintenance of immune self-tolerance and homeostasis. We previously reported that neonatal CD4+ T cells have an intrinsic ‘default’ mechanism to become Treg (neoTreg) cells in response to T-cell receptor (TCR) stimulation. However, the underlying mechanisms are unclear and the effects of neoTreg cells on regulating immune responses remain unknown. Due to their involvement in Foxp3 regulation, we examined the role of DNA methyltransferase 1 (DNMT1) and DNMT3b during the induction of neoTreg cells in the Foxp3gfp mice. The function of neoTreg cells was assessed in an acute allograft rejection model established in RAG2−/− mice with allograft cardiac transplantation and transferred with syngeneic CD4+ effector T cells. Following ex vivo TCR stimulation, the DNMT activity was increased threefold in adult CD4+ T cells, but not significantly increased in neonatal cells. However, adoptively transferred neoTreg cells significantly prolonged cardiac allograft survival (mean survival time 47 days, P < 0·001) and maintained Foxp3 expression similar to natural Treg cells. The neoTreg cells were hypomethylated at the conserved non-coding DNA sequence 2 locus of Foxp3 compared with adult Treg cells. The DNMT antagonist 5-aza-2′-deoxycytidine (5-Aza) induced increased Foxp3 expression in mature CD4+ T cells. 5-Aza-inducible Treg cells combined with continuous 5-Aza treatment prolonged graft survival. These results indicate that the ‘default’ pathway of neoTreg cell differentiation is associated with reduced DNMT1 and DNMT3b response to TCR stimulus. The neoTreg cells may be a strategy to alleviate acute allograft rejection. PMID:24944101

  1. Decreased Survival of Glioma Patients with Astrocytoma Grade IV (Glioblastoma Multiforme) Associated with Long-Term Use of Mobile and Cordless Phones

    PubMed Central

    Carlberg, Michael; Hardell, Lennart

    2014-01-01

    On 31 May 2011 the WHO International Agency for Research on Cancer (IARC) categorised radiofrequency electromagnetic fields (RF-EMFs) from mobile phones, and from other devices that emit similar non-ionising electromagnetic fields, as a Group 2B, i.e., a “possible”, human carcinogen. A causal association would be strengthened if it could be shown that the use of wireless phones has an impact on the survival of glioma patients. We analysed survival of 1678 glioma patients in our 1997–2003 and 2007–2009 case-control studies. Use of wireless phones in the >20 years latency group (time since first use) yielded an increased hazard ratio (HR) = 1.7, 95% confidence interval (CI) = 1.2–2.3 for glioma. For astrocytoma grade IV (glioblastoma multiforme; n = 926) mobile phone use yielded HR = 2.0, 95% CI = 1.4–2.9 and cordless phone use HR = 3.4, 95% CI = 1.04–11 in the same latency category. The hazard ratio for astrocytoma grade IV increased statistically significant per year of latency for wireless phones, HR = 1.020, 95% CI = 1.007–1.033, but not per 100 h cumulative use, HR = 1.002, 95% CI = 0.999–1.005. HR was not statistically significant increased for other types of glioma. Due to the relationship with survival the classification of IARC is strengthened and RF-EMF should be regarded as human carcinogen requiring urgent revision of current exposure guidelines. PMID:25325361

  2. Long-term survival in a patient with repeated resections for lung metastasis after hepatectomy for ruptured hepatocellular carcinoma: a case report

    PubMed Central

    Shih, Kai-Lun; Chen, Yang-Yuan; Teng, Tsung-Han; Soon, Maw-Soan

    2008-01-01

    Introduction Tumor rupture and pulmonary metastasis in patients with hepatocellular carcinoma are both associated with poor prognosis and treatment strategies are controversial. Case presentation Here we report a 50-year-old man with survival of over 90 months after undergoing an extended right lobectomy for a ruptured hepatocellular carcinoma and then repeated resections for pulmonary metastasis during the followup period. Conclusion This case report shows that surgical resection can be an effective treatment for patients with both ruptured hepatocellular carcinoma and pulmonary recurrences. PMID:18588711

  3. Epidemiology and long-term survival of pulmonary arterial hypertension in the Czech Republic: a retrospective analysis of a nationwide registry

    PubMed Central

    2014-01-01

    Background Pulmonary arterial hypertension (PAH) is a severe and progressive disease characterized by increased pulmonary vascular resistance, ultimately leading to right heart failure and death. Epidemiological data from national registries are growing worldwide, but are still unavailable in Eastern Europe. Methods A PAH registry was initiated in January 2007 using a nationwide network of echocardiographic centers and four diagnostic centers that specialize in PAH. All patients aged above 18 years, diagnosed with PAH and monitored between January 2000 and December 2007 were included. Patients diagnosed with PAH between January and December 2007 were classified as incident. The survival analyses were performed up to the end of 2010. Prognostic factors at the time of diagnosis were identified using uni- and multivariable Cox proportional hazard models. Results Overall, 191 patients were included (100 prevalent cases, 91 incident cases). Patients were predominantly female (n = 125) and had a mean age of 51.9 ± 16.9 years. Incident patients were significantly older at the time of diagnosis than prevalent patients (p < 0.001). Most patients (60.7%) had idiopathic PAH; 20.4% had PAH associated with congenital heart disease and 11.4% had PAH associated with connective tissue disease. Estimates of prevalence and incidence of PAH in adults were 22.4 cases per million and 10.7 cases per million per year, respectively. The 1-, 2- and 3-year survival rates in the incident PAH cohort were 89% (95% confidence intervals [CI] 83–95%), 78% (95% CI 70–87%) and 74% (95% CI 65–83%), respectively. Lower survival rates were significantly associated with higher age (hazard ratio [HR] 6.6 95% CI 1.4–30.9) and lower creatinine clearance (HR 3.3 95% CI 1.1–9.7). Conclusion This is the first study in Eastern Europe to describe the prevalence, incidence and survival of patients with PAH from a national representative registry. This registry from the Czech Republic

  4. Sources of variation in growth, form, and survival in dwarf and normal-stature pitch pines (Pinus rigida, Pinaceae) in long-term transplant experiments.

    PubMed

    Fang, Wei; Taub, Daniel R; Fox, Gordon A; Landis, R Matthew; Natali, Susan; Gurevitch, Jessica

    2006-08-01

    Determining the relative contributions of genetic and environmental factors to phenotypic variation is critical for understanding the evolutionary ecology of plant species, but few studies have examined the sources of phenotypic differentiation between nearby populations of woody plants. We conducted reciprocal transplant experiments to examine sources of variation in growth rate, form, survival, and maturation in a globally rare dwarf population of pitch pine (Pinus rigida) and in surrounding populations of normal-stature pitch pines on Long Island, New York. Transplants were monitored over a 6-yr period. The influence of seedling origin on height, growth rate, survival, and form (single-stemmed vs. multi-stemmed growth habit) was much smaller than the effect of transplanting location. Both planting site and seed origin were important factors in determining time to reproduction; seedlings originating from dwarf populations and seedlings planted at the normal-stature site reproduced earliest. These results suggest that many of the differences between dwarf and normal-stature pitch pines may be due more to plastic responses to environmental factors than to genetic differentiation among populations. Therefore, preservation of the dwarf pine habitat is essential for preserving dwarf pine communities; the dwarf pines cannot be preserved ex situ.

  5. Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL.

    PubMed

    Topp, Max S; Gökbuget, Nicola; Zugmaier, Gerhard; Degenhard, Evelyn; Goebeler, Marie-Elisabeth; Klinger, Matthias; Neumann, Svenja A; Horst, Heinz A; Raff, Thorsten; Viardot, Andreas; Stelljes, Matthias; Schaich, Markus; Köhne-Volland, Rudolf; Brüggemann, Monika; Ottmann, Oliver G; Burmeister, Thomas; Baeuerle, Patrick A; Nagorsen, Dirk; Schmidt, Margit; Einsele, Hermann; Riethmüller, Gert; Kneba, Michael; Hoelzer, Dieter; Kufer, Peter; Bargou, Ralf C

    2012-12-20

    Persistence or recurrence of minimal residual disease (MRD) after chemotherapy results in clinical relapse in patients with acute lymphoblastic leukemia (ALL). In a phase 2 trial of B-lineage ALL patients with persistent or relapsed MRD, a T cell-engaging bispecific Ab construct induced an 80% MRD response rate. In the present study, we show that after a median follow-up of 33 months, the hematologic relapse-free survival of the entire evaluable study cohort of 20 patients was 61% (Kaplan-Meier estimate). The hema-tologic relapse-free survival rate of a subgroup of 9 patients who received allogeneic hematopoietic stem cell transplantation after blinatumomab treatment was 65% (Kaplan-Meier estimate). Of the subgroup of 6 Philadelphia chromosome-negative MRD responders with no further therapy after blinatumomab, 4 are in ongoing hematologic and molecular remission. We conclude that blinatumomab can induce long-lasting complete remission in B-lineage ALL patients with persistent or recurrent MRD. The original study and this follow-up study are registered at www.clinicaltrials.gov as NCT00198991 and NCT00198978, respectively.

  6. Survival in air of Mytilus trossulus following long-term exposure to spilled Exxon Valdez crude oil in Prince William Sound.

    PubMed

    Thomas, R E; Harris, P M; Rice, S D

    1999-01-01

    Mussels, Mytilus trossulus, were sampled in 1996 from beaches in Prince William Sound (PWS) which contained residual oil resulting from the Exxon Valdez oil spill of March 1989, and from one beach which had been lightly oiled in 1989, but contained no residual oil in 1996. The latter mussels served as un-oiled references. Mussels were also collected from Tee Harbor, Southeast Alaska, to be used as an additional reference group. Where the size of the individuals in the resident population would permit, two size groups were sampled, 32-35 and 18-20 mm in length. Polynuclear aromatic hydrocarbon (PAH) concentrations in mussel tissue, and air survival time were determined for each group of mussels. Total PAH concentrations were significantly greater in tissue of mussels from oiled beds (0.6-2.0 micrograms g-1) than from references (0.01-0.12 microgram g-1) (P < 0.01). Oil-exposed mussels had significantly lower LT50 values (P < 0.05) for air survival than reference groups. Tolerance of small mussels to air exposure was significantly greater (P < 0.01) than large mussels in both the unoiled reference and oil exposed groups.

  7. Threshold of long-term survival of a coastal delphinid in anthropogenically degraded environment: Indo-Pacific humpback dolphins in Pearl River Delta

    PubMed Central

    Karczmarski, Leszek; Huang, Shiang-Lin; Chan, Stephen C.Y.

    2017-01-01

    Defining demographic and ecological threshold of population persistence can assist in informing conservation management. We undertook such analyses for the Indo-Pacific humpback dolphin (Sousa chinensis) in the Pearl River Delta (PRD) region, southeast China. We use adult survival estimates for assessments of population status and annual rate of change. Our estimates indicate that, given a stationary population structure and minimal risk scenario, ~2000 individuals (minimum viable population in carrying capacity, MVPk) can maintain the population persistence across 40 generations. However, under the current population trend (~2.5% decline/annum), the population is fast approaching its viability threshold and may soon face effects of demographic stochasticity. The population demographic trajectory and the minimum area of critical habitat (MACH) that could prevent stochastic extinction are both highly sensitive to fluctuations in adult survival. For a hypothetical stationary population, MACH should approximate 3000-km2. However, this estimate increases four-fold with a 5% increase of adult mortality and exceeds the size of PRD when calculated for the current population status. On the other hand, cumulatively all current MPAs within PRD fail to secure the minimum habitat requirement to accommodate sufficiently viable population size. Our findings indicate that the PRD population is deemed to become extinct unless effective conservation measures can rapidly reverse the current population trend. PMID:28230056

  8. Impact of local surgical treatment on survival in young women with T1 breast cancer: long-term results of a population-based cohort.

    PubMed

    Jeon, Ye Won; Choi, Jung Eun; Park, Heung Kyu; Kim, Ku Sang; Lee, Jee Yeon; Suh, Young Jin

    2013-04-01

    The aim of this study was to analyze the effect of the type of local surgical treatment on survival in young women aged less than 40 years with T1 breast cancer. We analyzed data from 3,512 patients aged ≤40 years old who were diagnosed with T1 breast cancer from the Korean Breast Cancer Registry database between January 1988 and December 2006 and underwent either breast-conserving therapy (BCT) or mastectomy. The overall survival (OS) and breast-cancer-specific survival (BCSS) were compared between BCT and mastectomy. Of the 3,512 patients analyzed, 1,951 (55.6 %) underwent BCT, and 1,561 (44.4 %) underwent mastectomy. The median follow-up period was 111.0 (79.0-131.5) months. Overall, the 10-year OS rates for BCT and mastectomy were 95 and 92.1 %, respectively (p = 00004), and the 10-year BCSS rates for BCT and mastectomy patients were 96.9 and 94.9 %, respectively (p = 0.12). In node-negative patients, no significant difference was observed in either the OS (adjusted hazard ratio [HR] 1.072; 95 % CI, 0.750-1.5332, p = 0.704) or BCSS (adjusted HR 0.988; 95 % CI, 0.620-1.574, p = 0.960) rate between the BCT and mastectomy groups. In node-positive patients, no significant difference was observed in the OS (adjusted HR 1.634; 95 % CI, 0.982-2.272, p = 0.59) and BCSS (adjusted HR 1.410; 95 % CI, 0.755-2.633, p = 0.281) rates between the BCT and mastectomy groups. In this large, population-based analysis of young women with T1 breast cancer, the OS and BCSS were not different between BCT and mastectomy.

  9. [A long-term survival case of far-advanced colon cancer with Virchow's lymph node and lung metastasis that responded to multidisciplinary therapy].

    PubMed

    Takahashi, Satoshi; Iiai, Tsuneo; Shimada, Yoshifumi; Kobayashi, Yasuo; Suda, Kazutaka; Iwaya, Akira; Maruyama, Satoshi; Tani, Tatsuo; Hatakeyama, Katsuyoshi

    2009-01-01

    The patient was a 73-year-old male. Under a diagnosis of advanced cecal colon cancer with metastasis to Virchow's and paraaortic lymph nodes and lungs, a laparoscopic-assisted ileocecal resection with D2 lymph node dissection was performed. Histological examination of the resected specimens revealed moderately-differentiated adenocarcinoma which had invaded the terminal ileum. The lesion was judged to be SI(ileum), N2, H0, P0, M1(Virchow's lymph node, No. 216, lungs), Stage IV. After the operation, he received chemotherapy with 5-FU/l-LV(RPMI method), LV/UFT, FOLFOX, FOLFIRI in succession, and cancer aggravation was generally controlled. He has survived for 3 years since operation, and shows good QOL under the treatment.

  10. Long-Term Sustainability of Evidence-Based Prevention Interventions and Community Coalitions Survival: a Five and One-Half Year Follow-up Study.

    PubMed

    Johnson, Knowlton; Collins, David; Shamblen, Steve; Kenworthy, Tara; Wandersman, Abraham

    2017-04-11

    This study examines (1) coalition survival, (2) prevalence of evidence-based prevention interventions (EBPIs) to reduce substance abuse implemented as part of the Tennessee Strategic Prevention Framework (SPF) State Incentive Grant (SIG), (3) EBPI sustainability, and (4) factors that predict EBPI sustainability. Secondary data were collected on 27 SPF SIG-funded coalitions and 88 EBPI and non-EBPI implementations. Primary data were collected by a telephone interview/web survey five and one-half years after the SPF SIG ended. Results from secondary data show that 25 of the 27 coalitions survived beyond the SPF SIG for one to five and one-half years; 19 coalitions (70%) were still active five and one-half years later. Further, 88 EBPIs and non-EBPIs were implemented by 27 county SPF SIG coalitions. Twenty-one (21) of 27 coalitions (78%) implemented one to three EBPIs, totaling 37 EBPI implementations. Based on primary survey data on 29 of the 37 EBPI implementations, 28 EBPIs (97%) were sustained between two and five and one-half years while 22 EBPI implementations (76%) were sustained for five and one-half years. When controlling for variability among coalitions (nesting of EBPIs in coalitions), increases in data resources (availability of five types of prevention data) was a strong predictor of length of EBPI sustainability. Positive change in extramural funding resources and level of expertise during SPF SIG implementation, as well as level of coalition formalization at the end of the SPF SIG predicted EBPI sustainability length. One intervention attribute (trialability) also predicted length of sustainability. Implications are discussed.

  11. The preoperative sensitive-modified Glasgow prognostic score is superior to the modified Glasgow prognostic score in predicting long-term survival for esophageal squamous cell carcinoma

    PubMed Central

    Tian, Rui; Zhang, Fei; Sun, Peng; Wu, Jing; Yan, Hong; Wu, Ai-Ran; Zhang, Min; Jiang, Yu-Lu; Lu, Yan-Hong; Xu, Qiu-Yan; Zhan, Xiao-Hong; Zhang, Rong-Xin; Qian, Li-Ting; He, Jie

    2016-01-01

    The present study was designed to investigate the prognostic significance of the preoperative sensitive-modified Glasgow prognostic score (S-mGPS) and its superiority in esophageal squamous cell carcinoma (ESCC). Clinicopathologic characteristics, preoperative albumin and C-reactive protein (CRP) levels were retrospectively collected in 442 patients who underwent transthoracic esophagectomy. The S-mGPS was calculated before surgery based on optimal cutoff values of 45.6 g/L for albumin and 10.0 mg/L for CRP. 360, 74 and 8 cases were assigned an mGPS of 0, 1 and 2, respectively. In contrast, the S-mGPS was 0 in 114, 1 in 258 and 2 in 70 patients. Of the 360 patients with an mGPS of 0, 246 migrated to the S-mGPS-1 group. Both mGPS and S-mGPS were significantly correlated with tumor length, depth of invasion, pathological tumor-node-metastasis (pTNM) stage and adjuvant treatment. In addition, they were significantly associated with disease free survival (DFS) and overall survival (OS) in univariate analysis. Furthermore, multivariate Cox regression analysis identified S-mGPS as an independent prognostic indicator for both DFS [hazard ratio (HR), 1.577; 95% confidence interval (CI), 1.149-2.163; P = 0.005] and OS (HR, 1.762; 95% CI, 1.250-2.484; P = 0.001), but not mGPS (HR, 0.957; 95% CI, 0.692-1.323; P = 0.790 for DFS and HR, 1.089; 95% CI, 0.781-1.517; P = 0.615 for OS, respectively). Moreover, subgroup analysis revealed that the prognostic impact of the S-mGPS was especially striking in pTNM stage II patients. The preoperative S-mGPS is superior to the mGPS as a prognostic predictor in patients with resectable ESCC. PMID:27528228

  12. [A Case of GIST of the Stomach with Long-Term Survival after Multidisciplinary Treatment, Including Four Surgical Resections of Liver Metastases].

    PubMed

    Kitakaze, Masatoshi; Hirao, Motohiro; Miyamoto, Atsushi; Hamakawa, Takuya; Yamamoto, Kazuyoshi; Nishikawa, Kazuhiro; Maeda, Sakae; Uemura, Mamoru; Miyake, Masakazu; Hama, Naoki; Miyazaki, Michihiko; Ikeda, Masataka; Nakamori, Shoji; Kiyokawa, Hiroki; Mano, Masayuki; Sekimoto, Mitsugu

    2016-11-01

    The most frequent relapse site of gastrointestinal stromal tumors(GIST)is the liver. We encountered a patient with longterm survival treated with multidisciplinary treatment, including4 hepatectomies for liver metastases. The patient was a woman aged 69 years at the time of the first medical treatment. She underwent total gastrectomy and S6 segmental hepatec- tomy for a stomach GIST with a hepatic metastasis. The tumor diameter was 24 cm and the mitotic figure was 65/50 HPF. According to the guidelines, it was diagnosed as a high risk GIST based on strong positive immunostaining for CD34 and c-kit. The tumor had metastasized to the liver and greater omentum. She took imatinib in the year following surgery. Because the GIST had spread to the lung1 8 months after the operation, she took imatinib again. Two years after the operation the pulmonary metastasis showed a clinical complete response(cCR)and the CR lasted for 4 years. Six years after the surgery she had a hepatic recurrence in S5, and she underwent an S5/4 partial hepatic resection. Seven years after the first operation, a liver S7 metastasis developed and she underwent S7 partial hepatectomy. Ten years after the first surgery, the GIST relapsed in liver S6 with right adrenal gland permeation. She underwent partial S6/7 liver resection and a right adrenal gland resection. She resumed takingimatinib after this surgical resection. Now, 11 years after the first operation, she is alive with an S1 hepatic recurrence taking sunitinib. Therefore, multidisciplinary treatment with surgical resection prolongs the survival of patients with resectable liver metastases of GIST.

  13. Atypical teratoid/rhabdoid tumor of the velum interpositum presenting as a spontaneous intraventricular hemorrhage in an infant: case report with long-term survival.

    PubMed

    Donovan, Daniel J; Smith, Alice B; Petermann, Gregory W

    2006-01-01

    Atypical teratoid/rhabdoid tumors (ATRT) of infancy are highly malignant neoplasms that are most common in the first 2 years of life. We present the case of a 3-month-old girl who presented with the acute onset of generalized seizures and was found to have a large spontaneous intraventricular hemorrhage. The blood masked an underlying ATRT of the velum interpositum in the midline of the lateral ventricles and roof of the third ventricle, the first reported case in this location. Serial imaging studies and two ventriculoscopic biopsies were required to establish the diagnosis of the tumor in this unique location and in the midst of an evolving hematoma. After surgical resection, the patient received adjuvant chemotherapy. At 4-year follow-up, the child is neurologically intact, meeting normal developmental milestones, and imaging studies show no evidence of tumor. ATRT were previously associated with an extremely poor prognosis, but more recent evidence with complete surgical resection and adjuvant chemotherapy shows extended survival in some cases, supporting an aggressive and comprehensive approach to give these patients the best chance for a good outcome. Spontaneous brain hemorrhage in a full-term infant requires a diligent and persistent search to rule out an underlying neoplasm.

  14. Investigating the impact of teachers' implementation practices on academic achievement in science during a long-term professional development program on the Science Writing Heuristic

    NASA Astrophysics Data System (ADS)

    Gunel, Murat

    This study is a part of a bigger project known as the Science Writing Heuristic (SWH) Partnership Professional Development Project, conducted at Iowa State University and the University of Iowa in association with the Iowa Department of Education to help improve science teaching. Overall, the goal of the project is to help practicing science teachers understand and apply a student-oriented instructional approach, using the SWH. The purpose of this research study was to examine the link between teachers' implementation of a student-oriented teaching approach through the SWH approach with embedded non-traditional writing practices and students' performances on standardized tests over a 3-year period. This study investigated the impact of 6 teachers' (3 high school teachers and 3 middle school teachers) implementation of the SWH approach on student standardized test scores over the 3-year period. A mixed method approach was adopted as a research method. A major premise underpinning this study is that in the rate of change differs by teachers, and that change is not a linear process for teachers. Results of the study indicated a differential across teachers in terms of improvement in pedagogical skills related to the SWH approach. Further, results showed that the SWH approach in-service program did have an impact on participating teachers' pedagogical practices. The majority of the participating teachers improved their pedagogical practices of implementing science inquiry through the SWH approach over the 3-year period of the professional development program. Further, when teachers' rankings were correlated against students' standardized test scores, the results indicated that as their implementation levels increased their students' test achievements also increased.

  15. What factors predict long-term survival and valve durability in patients with atrioventricular valve regurgitation in single-ventricle physiology?

    PubMed

    Jang, Woo Sung; Kim, Woong-Han; Choi, Kwangho; Lee, Jeong Ryul; Kim, Yong Jin; Kwon, Bo Sang; Kim, Gi Beom

    2013-08-01

    Although significant atrioventricular valve regurgitation (AVVR) is well known for its association with increased morbidity and mortality in patients with single-ventricle physiology, there is a lack of consensus in management of AVVR. The purpose of this study was to analyze the clinical outcomes in patients receiving AVV repair or replacement. From 2001 to 2010, a total of 33 patients (25 male and 8 female) with more than moderate-degree AVVR among 160 patients who underwent staged single-ventricle palliation were included. The median follow-up duration was 6.0 years (range 0.1-14.1). Valve repair (n = 27) or valve replacement (n = 6) was performed at the initial surgery. There were six late mortalities (18.18 %): five in the repair group and one in the replacement group and seven morbidities. Among patients with valve repair, 11 were required to undergo redo-valve operations (valve repair n = 6, valve replacement n = 5) due to deteriorated valve function. Initial shunt procedure (p = 0.04) and arrhythmia (p = 0.01) were risk factors for survival. Freedom from reoperation in the valve replacement group was higher than that in the valve repair group (67.0 ± 9.7 and 44.6 ± 11.2 % at 5 and 6 years, respectively, p = 0.03). Need for early repair (p = 0.02), presence of mitral- or tricuspid-dominant AVV (p = 0.005), and male sex (p = 0.04) were risk factors for valve durability. Early valve regurgitation affects valve durability. Thus, successful repair in the early stage may improve later outcomes. Therefore, aggressive valve surgery was required and AVV replacement might be one of the options for selected patients.

  16. Anti-CD45 Pretargeted Radioimmunotherapy using Bismuth-213: High Rates of Complete Remission and Long-Term Survival in a Mouse Myeloid Leukemia Xenograft Model

    SciTech Connect

    Pagel, John M; Kenoyer, Aimee L; Back, Tom; Hamlin, Donald K; Wilbur, D Scott; Fisher, Darrell R; Park, Steven I; Frayo, Shani; Axtman, Amanda; Orgun, Nural; Orozoco, Johnnie; Shenoi, Jaideep; Lin, Yukang; Gopal, Ajay K; Green, Damian J; Appelbaum, Frederick R; Press, Oliver W

    2011-07-21

    Pretargeted radioimmunotherapy (PRIT) using an anti-CD45 antibody (Ab)-streptavidin (SA) conjugate and DOTA-biotin labeled with β-emitting radionuclides has been explored as a strategy to decrease relapse and toxicity. α-emitting radionuclides exhibit high cytotoxicity coupled with a short path-length, potentially increasing the therapeutic index and making them an attractive alternative to β-emitting radionuclides for patients with Acute Myeloid Leukemia (AML). Accordingly, we have used 213Bi in mice with human leukemia xenografts. Results demonstrated excellent localization of 213Bi-DOTA-biotin to tumors with minimal uptake into normal organs. After 10 minutes, 4.5 ± 1.1% of the injected dose of 213Bi was delivered per gram of tumor. α imaging demonstrated uniform radionuclide distribution within tumor tissue 45 minutes after 213Bi-DOTA-biotin injection. Radiation absorbed doses were similar to those observed using a β-emitting radionuclide (90Y) in the same model. We conducted therapy experiments in a xenograft model using a single-dose of 213Bi-DOTA-biotin given 24 hours after anti-CD45 Ab-SA conjugate. Among mice treated with anti-CD45 Ab-SA conjugate followed by 800 μCi of 213Bi- or 90Y-DOTA-biotin, 80% and 20%, respectively, survived leukemia-free for >100 days with minimal toxicity. These data suggest that anti-CD45 PRIT using an α-emitting radionuclide may be highly effective and minimally toxic for treatment of AML.

  17. Low high-density lipoprotein cholesterol is a residual risk factor associated with long-term clinical outcomes in diabetic patients with stable coronary artery disease who achieve optimal control of low-density lipoprotein cholesterol.

    PubMed

    Ogita, Manabu; Miyauchi, Katsumi; Miyazaki, Tadashi; Naito, Ryo; Konishi, Hirokazu; Tsuboi, Shuta; Dohi, Tomotaka; Kasai, Takatoshi; Yokoyama, Takayuki; Okazaki, Shinya; Kurata, Takeshi; Daida, Hiroyuki

    2014-01-01

    Diabetes mellitus is recognized an independent risk factor for coronary artery disease (CAD) and mortality. Clinical trials have shown that statins significantly reduce cardiovascular events in diabetic patients. However, residual cardiovascular risk persists despite the achievement of target low-density lipoprotein cholesterol (LDL-C) levels with statin. High-density lipoprotein cholesterol (HDL-C) is an established coronary risk factor that is independent of LDL-C levels. We evaluated the impact of HDL-C on long-term mortality in diabetic patients with stable CAD who achieved optimal LDL-C. We enrolled 438 consecutive diabetic patients who were scheduled for percutaneous coronary intervention between 2004 and 2007 at our institution. We identified 165 patients who achieved target LDL-C <100 mg/dl. Patients were stratified into two groups according to HDL-C levels (low HDL-C group, baseline HDL-C <40 mg/dl; high HDL-C group, ≥40 mg/dl). Major adverse cardiac events (MACE) that included all-cause death, acute coronary syndrome, and target lesion revascularization were evaluated between the two groups. The median follow-up period was 946 days. The rate of MACE was significantly higher in diabetic patients with low-HDL-C who achieved optimal LDL-C (6.9 vs 17.9 %, log-rank P = 0.030). Multivariate Cox regression analysis showed that HDL-C is significantly associated with clinical outcomes (adjusted hazard ratio for MACE 1.33, 95 % confidence interval 1.01-1.75, P = 0.042). Low HDL-C is a residual risk factor that is significantly associated with long-term clinical outcomes among diabetic patients with stable CAD who achieve optimal LDL-C levels.

  18. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

    PubMed Central

    James, Nicholas D; Sydes, Matthew R; Clarke, Noel W; Mason, Malcolm D; Dearnaley, David P; Spears, Melissa R; Ritchie, Alastair W S; Parker, Christopher C; Russell, J Martin; Attard, Gerhardt; de Bono, Johann; Cross, William; Jones, Rob J; Thalmann, George; Amos, Claire; Matheson, David; Millman, Robin; Alzouebi, Mymoona; Beesley, Sharon; Birtle, Alison J; Brock, Susannah; Cathomas, Richard; Chakraborti, Prabir; Chowdhury, Simon; Cook, Audrey; Elliott, Tony; Gale, Joanna; Gibbs, Stephanie; Graham, John D; Hetherington, John; Hughes, Robert; Laing, Robert; McKinna, Fiona; McLaren, Duncan B; O'Sullivan, Joe M; Parikh, Omi; Peedell, Clive; Protheroe, Andrew; Robinson, Angus J; Srihari, Narayanan; Srinivasan, Rajaguru; Staffurth, John; Sundar, Santhanam; Tolan, Shaun; Tsang, David; Wagstaff, John; Parmar, Mahesh K B

    2016-01-01

    Summary Background Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. Methods Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m2) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). Findings 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60–71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6

  19. Novel antifouling agent--zinc pyrithione: short- and long-term effects on survival and reproduction of the marine polychaete Dinophilus gyrociliatus.

    PubMed

    Marcheselli, Marco; Conzo, Francesco; Mauri, Marina; Simonini, Roberto

    2010-06-10

    The recent ban on TBT in boat antifouling paints has resulted in a large employment of the biocide zinc pyrithione (ZnPT) as substitute. Despite concerns of its environmental toxicity at ultra-trace concentrations, ZnPT has received little attention, as it was assumed to photo-degrade easily. However, recent evidence has suggested that ZnPT degrades only partially, and persists in the marine environment, especially where the influence of light is limited, such as in harbours. Short-term acute toxicity tests and life table response experiments (LTREs) were performed to evaluate the effects of ZnPT on the polychaete Dinophilus gyrociliatus at both individual and population level. The 96h-LC(50) values for ZnPT on D. gyrociliatus were 7.8 and 11.5nM under dark and 12h light/12h dark conditions, respectively. In LTREs, laboratory cultured cohorts of D. gyrociliatus were exposed to sublethal concentrations of ZnPT (0.5 and 1nM) and compared to a control cohort. The survival among individuals exposed to the highest concentration decreased already during the 2nd week of life with respect to the control. The effects of the biocide on fecundity were even more evident: ZnPT caused a considerable reduction in both the exposed groups. The demographic approach applied here succeeded in identifying ZnPT effects both on the biological cycle and on the growth potential of polychaete D. gyrociliatus. The net growth rate (R(0)) appeared to be the demographic parameter most sensitive to ZnPT, as the biocide exposure was associated with a sharp decline of R(0) in both the 0.5 and the 1nM groups (-41% and -63%, respectively) in comparison to the control cohort. The population growth rate lambda (often used as an index of population fitness) and the life expectancy e(0) were also significantly reduced, while ZnPT exposure did not affect the generation time T. These results highlight the potential ecological threat posed by the biocide ZnPT, even at the very low tested concentrations

  20. Infective endocarditis: determinants of long term outcome

    PubMed Central

    Netzer, R O M; Altwegg, S C; Zollinger, E; Täuber, M; Carrel, T; Seiler, C

    2002-01-01

    Objective: To evaluate predictors of long term prognosis in infective endocarditis. Design: Retrospective cohort study. Setting: Tertiary care centre. Patients: 212 consecutive patients with infective endocarditis between 1980 and 1995 Main outcome measures: Overall and cardiac mortality; event-free survival; and the following events: recurrence, need for late valve surgery, bleeding and embolic complications, cerebral dysfunction, congestive heart failure. Results: During a mean follow up period of 89 months (range 1–244 months), 56% of patients died. In 180 hospital survivors, overall and cardiac mortality amounted to 45% and 24%, respectively. By multivariate analysis, early surgical treatment, infection by streptococci, age < 55 years, absence of congestive heart failure, and > 6 symptoms or signs of endocarditis during active infection were predictive of improved overall long term survival. Independent determinants of event-free survival were infection by streptococci and age < 55 years. Event-free survival was 17% at the end of follow up both in medically–surgically treated patients and in medically treated patients. Conclusions: Long term survival following infective endocarditis is 50% after 10 years and is predicted by early surgical treatment, age < 55 years, lack of congestive heart failure, and the initial presence of more symptoms of endocarditis. PMID:12067947

  1. Long-term environmental stewardship.

    SciTech Connect

    Nagy, Michael David

    2010-08-01

    The purpose of this Supplemental Information Source Document is to effectively describe Long-Term Environmental Stewardship (LTES) at Sandia National Laboratories/New Mexico (SNL/NM). More specifically, this document describes the LTES and Long-Term Stewardship (LTS) Programs, distinguishes between the LTES and LTS Programs, and summarizes the current status of the Environmental Restoration (ER) Project.

  2. Long-term urethral catheterisation.

    PubMed

    Turner, Bruce; Dickens, Nicola

    This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

  3. Presynaptic long-term plasticity

    PubMed Central

    Yang, Ying; Calakos, Nicole

    2013-01-01

    Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity. PMID:24146648

  4. [Long-term survival of a breast cancer patient with carcinomatous pleuritis and carcinomatous cardiac tamponade successfully treated by multimodality therapy].

    PubMed

    Tanaka, Yosuke; Tsuboi, Kaori; Yamamoto, Akira; Tsuda, Shoichi; Tsujii, Shigehiro; Yagi, Ken; Kitamura, Tatsuhiko

    2015-04-01

    A 69-year old woman was admitted to our hospital because of dyspnea and pain in her left breast. Computed tomography revealed a massive quantity of left pleural effusion, a tumor in the left breast(5 cm in diameter), left cervical and supraclavicular lymph node metastasis, and a large left axillary metastatic mass. Based on a core needle biopsy, her breast tumor was diagnosed pathologically as scirrhous carcinoma, which was positive for estrogen receptor/progesterone receptor and negative for HER2 using the FISH assay, and left pleural metastasis was diagnosed cytologically. The carcinomatous pleural effusion was successfully controlled using pleural instillations of pirarubicin HCl and OK-432 after pleural drainage. A near clinical complete response was achieved by EC systemic chemotherapy(6 months)followed by endocrine therapy(letrozole), but 3 months later she was diagnosed cytologically with carcinomatous cardiac tamponade. After operative pericardial drainage, intrapericardial instillations of cisplatin and OK-432 successfully prevented re-accumulation of pericardial effusion. Systemic chemotherapy(weekly paclitaxel)for 11 months and endocrine therapy(letrozole)resulted in a clinical complete response. One year and 10 months after pericardial drainage, she underwent surgery(mastectomy and axillary lymph node dissection level II)because of two small tumors in the left breast which were found to be malignant using PET-CT. One tumor(diameter 1.6 cm)was found pathologically to consist of degenerated cancer cells, and another tumor(diameter 2 cm)was diagnosed as recurrent cancer. There was no lymph node metastasis in the axilla except for a single mass(1.4×0.7×0.3 cm), which was composed of extremely degenerative and necrotic non-lymphoid cancerous tissue. Since having the surgery, she has not experienced recurrence on hormone therapy with fulvestrant, and to date she is still alive, 3 years and 5 months since the left pleural metastasis episode.

  5. Long term complications of diabetes

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000327.htm Long-term complications of diabetes To use the sharing features on this page, ... other tests. All these may help you keep complications of diabetes away. You will need to check your blood ...

  6. Low-dose donor bone marrow cells and splenocytes plus adenovirus encoding for CTLA4Ig gene promote stable mixed chimerism and long-term survival of rat cardiac allografts.

    PubMed

    Jin, Y-Z; Zhang, Q-Y; Xie, S-S

    2003-12-01

    Co-stimulatory blockade combined with donor bone marrow transfusion engenders stable mixed chimerism and robust tolerance to various organ and cell transplants. However, repeated administration of costly agents to block the co-stimulatory pathway and the high doses of donor bone marrow cells (BMCs) used in most protocols are impeding clinical development of this strategy. To circumvent these shortcomings, we developed a plan in which repeated administration of costly agents was replaced by a single injection of adenovirus containing the gene of interest, and the high dose of donor BMCs replaced by a mixture of low-dose donor BMCs and splenocytes (SPLCs). Cardiac allografts from DA(RT-1(a)) rats were transplanted heterotopically into the abdomens of LEW(RT-1(1)) rats. A cocktail of adenovirus containing CTLA4Ig gene (AdCTLA4Ig), donor BMCs (100 x 10(6)), and SPLCs (50 x 10(6)) was administered to recipients via the portal vein immediately after grafting (n = 6). Treatment with regimens, including AdCTLA4Ig only, AdCTLA4Ig plus donor BMCs, and AdCTLA4Ig plus donor SPLCs, significantly prolonged cardiac allograft survival in recipient rats, while animals that received no treatment or treatment with control adenovirus (AdLacZ) promptly rejected their allografts. Nevertheless, LEW recipients treated with AdCTLA4Ig and the mixture of a low dose of donor BMCs and SPLCs developed stable mixed chimerism, rendering them long-term survivors of cardiac allografts that also accepted skin grafts from the donor but not the third-party strain. We conclude that blockade of CD28-B7 pathway with AdCTLA4Ig plus a mixture of low doses of donor BMCs and SPLCs is a feasible strategy to induce long-term mixed chimerism with a potential application for clinical development.

  7. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group.

    PubMed Central

    Malmberg, K.

    1997-01-01

    OBJECTIVES: To test the hypothesis that intensive metabolic treatment with insulin-glucose infusion followed by multidose insulin treatment in patients with diabetes mellitus and acute myocardial infarction improves the prognosis. DESIGN: Patients with diabetes mellitus and acute myocardial infarction were randomly allocated standard treatment plus insulin-glucose infusion for at least 24 hours followed by multidose insulin treatment or standard treatment (controls). SUBJECTS: 620 patients were recruited, of whom 306 received intensive insulin treatment and 314 served as controls. MAIN OUTCOME MEASURE: Long term all cause mortality. RESULTS: The mean (range) follow up was 3.4 (1.6-5.6) years. There were 102 (33%) deaths in the treatment group compared with 138 (44%) deaths in the control group (relative risk (95% confidence interval) 0.72 (0.55 to 0.92); P = 0.011). The effect was most pronounced among the predefined group that included 272 patients without previous insulin treatment and at a low cardiovascular risk (0.49 (0.30 to 0.80); P = 0.004). CONCLUSION: Insulin-glucose infusion followed by intensive subcutaneous insulin in diabetic patients with acute myocardial infarction improves long term survival, and the effect seen at one year continues for at least 3.5 years, with an absolute reduction in mortality of 11%. This means that one life was saved for nine treated patients. The effect was most apparent in patients who had not previously received insulin treatment and who were at a low cardiovascular risk. PMID:9169397

  8. Long-term complications of splenectomy in adult immune thrombocytopenia

    PubMed Central

    Thai, Lan-Huong; Mahévas, Matthieu; Roudot-Thoraval, Françoise; Limal, Nicolas; Languille, Laetitia; Dumas, Guillaume; Khellaf, Mehdi; Bierling, Philippe; Michel, Marc; Godeau, Bertrand

    2016-01-01

    Abstract The recent large decrease in splenectomy use for chronic immune thrombocytopenia (ITP) is partly due to still-unsolved questions about long-term safety. We performed the first single-center exposed/unexposed cohort study evaluating the long-term incidence of splenectomy complications in patients with primary ITP. Overall, 83 patients who underwent splenectomy more than 10 years ago (exposed) were matched with 83 nonsplenectomized patients (unexposed) on the date of ITP diagnosis ±5 years, age and gender. After a median follow-up of 192 months (range 0.5–528), 43 patients (52%) achieved overall response after splenectomy. Splenectomized patients experienced more venous thromboembolism (VTE) than controls (n = 13 vs n = 2, P = 0.005). On multivariate analysis, splenectomy was an independent risk factor of VTE (hazard ratio = 4.006, P = 0.032 [95% confidence interval: 1.13–14.21]). Splenectomized patients presented more severe infections on long-term follow-up: all required hospitalization, and 5/26 (19%) infections led to severe sepsis or septic shock and to death for 3 cases (none in controls). However, the incidence of malignancy was similar in both groups, as was cardiovascular risk, which appeared to be related more to ITP than splenectomy. Finally, splenectomy did not significantly decrease overall survival. Despite the risk of thrombosis and severe sepsis, splenectomy remains an effective and curative treatment for ITP. PMID:27902585

  9. Adding Celecoxib With or Without Zoledronic Acid for Hormone-Naïve Prostate Cancer: Long-Term Survival Results From an Adaptive, Multiarm, Multistage, Platform, Randomized Controlled Trial.

    PubMed

    Mason, Malcolm D; Clarke, Noel W; James, Nicholas D; Dearnaley, David P; Spears, Melissa R; Ritchie, Alastair W S; Attard, Gerhardt; Cross, William; Jones, Rob J; Parker, Christopher C; Russell, J Martin; Thalmann, George N; Schiavone, Francesca; Cassoly, Estelle; Matheson, David; Millman, Robin; Rentsch, Cyrill A; Barber, Jim; Gilson, Clare; Ibrahim, Azman; Logue, John; Lydon, Anna; Nikapota, Ashok D; O'Sullivan, Joe M; Porfiri, Emilio; Protheroe, Andrew; Srihari, Narayanan Nair; Tsang, David; Wagstaff, John; Wallace, Jan; Walmsley, Catherine; Parmar, Mahesh K B; Sydes, Matthew R

    2017-03-13

    Purpose Systemic Therapy for Advanced or Metastatic Prostate Cancer: Evaluation of Drug Efficacy is a randomized controlled trial using a multiarm, multistage, platform design. It recruits men with high-risk, locally advanced or metastatic prostate cancer who were initiating long-term hormone therapy. We report survival data for two celecoxib (Cel)-containing comparisons, which stopped accrual early at interim analysis on the basis of failure-free survival. Patients and Methods Standard of care (SOC) was hormone therapy continuously (metastatic) or for ≥ 2 years (nonmetastatic); prostate (± pelvic node) radiotherapy was encouraged for men without metastases. Cel 400 mg was administered twice a day for 1 year. Zoledronic acid (ZA) 4 mg was administered for six 3-weekly cycles, then 4-weekly for 2 years. Stratified random assignment allocated patients 2:1:1 to SOC (control), SOC + Cel, or SOC + ZA + Cel. The primary outcome measure was all-cause mortality. Results were analyzed with Cox proportional hazards and flexible parametric models adjusted for stratification factors. Results A total of 1,245 men were randomly assigned (Oct 2005 to April 2011). Groups were balanced: median age, 65 years; 61% metastatic, 14% N+/X M0, 25% N0M0; 94% newly diagnosed; median prostate-specific antigen, 66 ng/mL. Median follow-up was 69 months. Grade 3 to 5 adverse events were seen in 36% SOC-only, 33% SOC + Cel, and 32% SOC + ZA + Cel patients. There were 303 control arm deaths (83% prostate cancer), and median survival was 66 months. Compared with SOC, the adjusted hazard ratio was 0.98 (95% CI, 0.80 to 1.20; P = .847; median survival, 70 months) for SOC + Cel and 0.86 (95% CI, 0.70 to 1.05; P =.130; median survival, 76 months) for SOC + ZA + Cel. Preplanned subgroup analyses in men with metastatic disease showed a hazard ratio of 0.78 (95% CI, 0.62 to 0.98; P = .033) for SOC + ZA + Cel. Conclusion These data show no overall evidence of improved survival with Cel. Preplanned

  10. Long-term schisandrin B treatment mitigates age-related impairments in mitochondrial antioxidant status and functional ability in various tissues, and improves the survival of aging C57BL/6J mice.

    PubMed

    Ko, Kam Ming; Chen, Na; Leung, Hoi Yan; Leong, Eriol P K; Poon, Michel K T; Chiu, Po Yee

    2008-01-01

    Mitochondrial decay is a major cause of aging, leading to the subsequent death of aerobic organisms including humans. In the present study, we examined the effects of supplementation with schisandrin B (Sch B, a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis), administered at 0.012% (w/w) of diet, starting from the age of 36 weeks, on age-dependent changes in mouse mitochondrial antioxidant status and functional ability in various tissues (brain, heart, liver, and kidney) up to the age of 120 weeks. We also monitored survival of male and female C57BL/6J mice. Aging caused progressive impairment in mitochondrial antioxidant status in various tissues, as evidenced by decreases in reduced glutathione and alpha-tocopherol levels, and Mn-superoxide dismutase activity. Impairments in mitochondrial antioxidant status were invariably associated with increases in mitochondria-driven reactive oxygen species (ROS) production in tissue homogenates, as well as decreased mitochondrial ATP-generation capacities (ATP-GCs), in all tested tissues. Diet supplementation with Sch B ameliorated impairment in mitochondrial antioxidant status during aging. The effects were more pronounced in younger than in older mice, when compared to age-matched non-supplemented controls. Sch B supplementation also suppressed mitochondria-driven ROS production and enhanced mitochondrial ATP-GC in various tissues during aging. The beneficial effects of Sch B supplementation on mitochondrial antioxidant status and functional ability were paralleled by survival improvement in aging male mice, when compared with controls. Sch B supplementation also improved the survival in female mice. In conclusion, long-term Sch B supplementation mitigated age-dependent impairments in mitochondrial antioxidant capacity and functional ability, thereby retarding the aging process in mice, particularly during early aging.

  11. Long-term survival after high-dose chemotherapy followed by peripheral stem cell rescue for high-risk, locally advanced/inflammatory, and metastatic breast cancer.

    PubMed

    VanderWalde, A; Ye, W; Frankel, P; Asuncion, D; Leong, L; Luu, T; Morgan, R; Twardowski, P; Koczywas, M; Pezner, R; Paz, I B; Margolin, K; Wong, J; Doroshow, J H; Forman, S; Shibata, S; Somlo, G

    2012-08-01

    Patients with high-risk locally advanced/inflammatory and oligometastatic (≤3 sites) breast cancer frequently relapse or experience early progression. High-dose chemotherapy combined with peripheral stem cell rescue may prolong progression-free survival/relapse-free survival (PFS/RFS) and overall survival (OS). In this study, patients initiated high-dose chemotherapy with STAMP-V (carboplatin, thiotepa, and cyclophosphamide), ACT (doxorubicin, paclitaxel, and cyclophosphamide), or tandem melphalan and STAMP-V. Eighty-six patients were diagnosed with locally advanced/inflammatory (17 inflammatory) breast cancer, and 12 were diagnosed with oligometastatic breast cancer. Median follow-up was 84 months (range, 6-136 months) for patients with locally advanced cancer and 40 months (range, 24-62 months) for those with metastatic cancer. In the patients with locally advanced cancer, 5-year RFS and OS were 53% (95% CI, 41%-63%) and 71% (95% CI, 60%-80%), respectively, hormone receptors were positive in 74%, and HER2 overexpression was seen in 23%. In multivariate analysis, hormone receptor-positive disease and lower stage were associated with better 5-year RFS (60% for ER [estrogen receptor]/PR [progesterone receptor]-positive versus 30% for ER/PR-negative; P < .01) and OS (83% for ER/PR-positive versus 38% for ER/PR-negative; P < .001). In the patients with metastatic cancer, 3-year PFS and OS were 49% (95% CI, 19%-73%) and 73% (95% CI, 38%-91%), respectively. The favorable long-term RFS/PFS and OS for high-dose chemotherapy with peripheral stem cell rescue in this selected patient population reflect the relative safety of the procedure and warrant validation in defined subgroups through prospective, randomized, multi-institutional trials.

  12. Characteristics of Long-Term Survivors of Epithelial Ovarian Cancer

    PubMed Central

    Cress, Rosemary D.; Chen, Yingjia S.; Morris, Cyllene R.; Petersen, Megan; Leiserowitz, Gary S.

    2015-01-01

    Objective To identify characteristics associated with long-term survival forepithelial ovarian cancer patients using the California Cancer Registry. Methods A descriptive analysis of survival of all California residents diagnosed with epithelial ovarian cancer between 1994 and 2001 was conducted using patients identified through the cancer registry with follow up through 2011. Characteristics of the patients who survived more than 10 years (long-term survivors) were compared to three other cohorts: patients who survived less than 2 years, those who survived at least 2 but no more than 5 years, and those who survived at least 5 but no more than 10 years. Results A total of 3,582 out of 11,541 (31% CI=30.2%, 31.8%) of the patients survived more than 10 years. Younger age, early stage, low-grade, and non-serous histology were significant predictors of long-term survival, but long-term survivors also included women with high-risk cancer. Conclusion Long-term survival is not unusual in patients with epithelial ovarian cancer, even in those with high-risk disease. Many of the prognostic factors are well known, but it remains to be determined why some patients with advanced stage high-grade cancers survive longer than others with the same histology. These findings are important for patient counseling. PMID:26244529

  13. Use of Cox's Cure Model to Establish Clinical Determinants of Long-Term Disease-Free Survival in Neoadjuvant-Chemotherapy-Treated Breast Cancer Patients without Pathologic Complete Response.

    PubMed

    Asano, Junichi; Hirakawa, Akihiro; Hamada, Chikuma; Yonemori, Kan; Hirata, Taizo; Shimizu, Chikako; Tamura, Kenji; Fujiwara, Yasuhiro

    2013-01-01

    In prognostic studies for breast cancer patients treated with neoadjuvant chemotherapy (NAC), the ordinary Cox proportional-hazards (PH) model has been often used to identify prognostic factors for disease-free survival (DFS). This model assumes that all patients eventually experience relapse or death. However, a subset of NAC-treated breast cancer patients never experience these events during long-term follow-up (>10 years) and may be considered clinically "cured." Clinical factors associated with cure have not been studied adequately. Because the ordinary Cox PH model cannot be used to identify such clinical factors, we used the Cox PH cure model, a recently developed statistical method. This model includes both a logistic regression component for the cure rate and a Cox regression component for the hazard for uncured patients. The purpose of this study was to identify the clinical factors associated with cure and the variables associated with the time to recurrence or death in NAC-treated breast cancer patients without a pathologic complete response, by using the Cox PH cure model. We found that hormone receptor status, clinical response, human epidermal growth factor receptor 2 status, histological grade, and the number of lymph node metastases were associated with cure.

  14. Long-term sequelae of electrical injury

    PubMed Central

    Wesner, Marni L.; Hickie, John

    2013-01-01

    Abstract Objective To summarize the current evidence-based knowledge about the long-term sequelae of injuries from electrical current. Quality of evidence MEDLINE was searched for English-language articles published in the past 20 years using the following search terms: electrical, injuries, wound, trauma, accident, sequelae, long-term, follow-up, and aftereffects. For obvious reasons, it is unethical to randomly study electrical injury in controlled clinical trials. By necessity, this topic is addressed in less-rigorous observational and retrospective work and case studies. Therefore, the strength of the literature pertaining to the long-term sequelae of electrical injury is impaired by the necessity of retrospective methods and case studies that typically describe small cohorts. Main message There are 2 possible consequences of electrical injury: the person either survives or dies. For those who survive electrical injury, the immediate consequences are usually obvious and often require extensive medical intervention. The long-term sequelae of the electrical injury might be more subtle, pervasive, and less well defined, but can include neurologic, psychological, and physical symptoms. In the field of compensation medicine, determining causation and attributing outcome to an injury that might not result in objective clinical findings becomes a considerable challenge. Conclusion The appearance of these consequences of electrical injury might be substantially delayed, with onset 1 to 5 or more years after the electrical injury. This poses a problem for patients and health care workers, making it hard to ascribe symptoms to a remote injury when they might not arise until well after the incident event. PMID:24029506

  15. Long-term Survival Outcomes Following Internal Mammary Node Irradiation in Stage II-III Breast Cancer: Results of a Large Retrospective Study With 12-Year Follow-up

    SciTech Connect

    Chang, Jee Suk; Park, Won; Kim, Yong Bae; Lee, Ik Jae; Keum, Ki Chang; Lee, Chang Geol; Choi, Doo Ho; Suh, Chang-Ok; Huh, Seung Jae

    2013-08-01

    Purpose: To examine the effect of internal mammary node irradiation (IMNI) on disease-free survival (DFS) and overall survival (OS) in breast cancer patients treated with modified radical mastectomy and postoperative radiation therapy. Methods and Materials: Between 1994 and 2002, 396 patients with stage II-III breast cancer were treated with postmastectomy radiation therapy with (n=197) or without (n=199) IMNI. Patients who received neoadjuvant chemotherapy were excluded. IMNI was administered at the clinical discretion of the treating physician. Median RT dose was 50.4 Gy (range, 45.0-59.4 Gy) in 28 fractions, with inclusion of the supraclavicular fossa in 96% of patients. Adjuvant chemotherapy was administered to 99.7% of the patients and endocrine therapy to 53%. Results: The median follow-up was 149 months (range, 124-202). IMNI patients had more advanced nodal stage and non-high grade tumors than those without IMNI (P<.001). Otherwise, disease and treatment characteristics were well balanced. The 10-year DFS with and without IMNI was 65% and 57%, respectively (P=.05). Multivariate analysis demonstrated that IMNI was an independent, positive predictor of DFS (hazard ratio [HR], 0.70; P=.02). Benefits of IMNI in DFS were seen most apparently in N2 patients (HR, 0.44; 95% confidence interval [CI], 0.26-0.74) and inner/central tumors (HR, 0.55; 95% CI, 0.34-0.90). The 10-year OS with and without IMNI was 72% and 66%, respectively (P=.62). The 10-year DFS and OS were 61%, and 69%, respectively. Conclusions: Internal mammary node irradiation significantly improved DFS in postmastectomy breast cancer patients. Pending long-term results from randomized trials, treatment of internal mammary nodes should be considered in postmastectomy radiation therapy.

  16. Workshop on long-term contraceptives.

    PubMed

    1996-01-01

    The National Population Council Secretariat (NPCS) of Ghana held a three-day workshop on long-term contraceptives in 1996 in collaboration with the Ministry of Health, the Association of Voluntary Surgical Contraception, and the Johns Hopkins Population Communication Services. The session was funded by USAID. The executive director of NPCS, Dr. Richard Turkson, said that the slow rate of contraceptive acceptance was an obstacle to population control despite political concern that rapid population growth exerted an adverse impact on the economy. Only 10% of married women were using long-term or permanent methods of contraception. The hope was voiced that the participants would devise practical and cost-effective education, information, and communication (IEC) strategies to boost the demand for long-term contraceptive methods among sexually active people in Ghana. It was essential that these strategies and activities were based on a realist assessment of the demographic and social situation of the country. The examination of case studies in cultures similar to Ghana would also offer valuable lessons. The factors that hinder the acceptance of long-term methods include misconceptions, myths, and false rumors rooted in a general lack of knowledge among the people. Participants were urged to come up with strategies to counter these problems, and service providers were encouraged to improve their knowledge about contraceptive methods and counseling skills. Male involvement in contraception was also advocated. Statistics show that most Ghanians practicing contraception were using short-term methods such as foaming tablets, pills, and condoms. However, it is necessary to shift to long-term methods such as injectables, implants, and sterilization in order to achieve significant reductions in fertility.

  17. Long-term data archiving

    SciTech Connect

    Moore, David Steven

    2009-01-01

    Long term data archiving has much value for chemists, not only to retain access to research and product development records, but also to enable new developments and new discoveries. There are some recent regulatory requirements (e.g., FDA 21 CFR Part 11), but good science and good business both benefit regardless. A particular example of the benefits of and need for long term data archiving is the management of data from spectroscopic laboratory instruments. The sheer amount of spectroscopic data is increasing at a scary rate, and the pressures to archive come from the expense to create the data (or recreate it if it is lost) as well as its high information content. The goal of long-term data archiving is to save and organize instrument data files as well as any needed meta data (such as sample ID, LIMS information, operator, date, time, instrument conditions, sample type, excitation details, environmental parameters, etc.). This editorial explores the issues involved in long-term data archiving using the example of Raman spectral databases. There are at present several such databases, including common data format libraries and proprietary libraries. However, such databases and libraries should ultimately satisfy stringent criteria for long term data archiving, including readability for long times into the future, robustness to changes in computer hardware and operating systems, and use of public domain data formats. The latter criterion implies the data format should be platform independent and the tools to create the data format should be easily and publicly obtainable or developable. Several examples of attempts at spectral libraries exist, such as the ASTM ANDI format, and the JCAMP-DX format. On the other hand, proprietary library spectra can be exchanged and manipulated using proprietary tools. As the above examples have deficiencies according to the three long term data archiving criteria, Extensible Markup Language (XML; a product of the World Wide Web

  18. A new image for long-term care.

    PubMed

    Wager, Richard; Creelman, William

    2004-04-01

    To counter widely held negative images of long-term care, managers in the industry should implement quality-improvement initiatives that include six key strategies: Manage the expectations of residents and their families. Address customers' concerns early. Build long-term customer satisfaction. Allocate resources to achieve exceptional outcomes in key areas. Respond to adverse events with compassion. Reinforce the facility's credibility.

  19. Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

    SciTech Connect

    Feng, Felix Y.; Blas, Kevin; Olson, Karin; Stenmark, Matthew; Sandler, Howard; Hamstra, Daniel A.

    2013-05-01

    Purpose: To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). Methods and Materials: A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. Results: The median follow-up time was 64 months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. Conclusion: For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to 10.

  20. Long-term results of endobronchial brachytherapy: A curative treatment?

    SciTech Connect

    Hennequin, Christophe . E-mail: christophe.hennequin@sls.ap-hop-paris.fr; Bleichner, Olivier; Tredaniel, Jean; Quero, Laurent; Sergent, Guillaume; Zalcman, Gerard; Maylin, Claude

    2007-02-01

    Purpose: To evaluate outcomes after high-dose-rate endobronchial brachytherapy (HDR-EBBT) for limited lung carcinoma. Methods: A total of 106 patients with endobronchial lung cancer and not eligible for surgery or external beam radiotherapy, without nodal or visceral metastases, were treated with HDR-EBBT. They had developed disease relapse after surgery (n = 43) or external beam radiotherapy (n = 27) or had early lung cancer with respiratory insufficiency (n = 36). Treatment consisted of six fractions of 5 or 7 Gy, usually delivered 1 cm from the source. Results: The complete histologic response rate, evaluated at 3 months after HDR-EBBT, was 59.4%. At 3 and 5 years, the local control, overall survival, and cause-specific survival rates were 60.3% and 51.6%, 47.4 and 24%, and 67.9 and 48.5%, respectively. Factors significantly associated with local failure were high tumor volume (tumor length >2 cm, bronchial obstruction >25%, tumor visibility on CT scan) and previous endoscopic treatment. Cause-specific survival, but not overall survival, was significantly associated with local control, probably because of the high rate of deaths not related to lung cancer. Five deaths were attributed to the HDR-EBBT procedure (two from fatal hemoptysis and three from bronchial necrosis). Conclusion: High-dose-rate-EBBT achieved a long-term cause-specific survival rate of 50% of the patients with localized endobronchial carcinoma and could be considered curative.

  1. Discontinuation of Hypomethylating Agent Therapy in Patients with Myelodysplastic Syndromes or Acute Myelogenous Leukemia in Complete Remission or Partial Response: Retrospective Analysis of Survival after Long-term Follow-up

    PubMed Central

    Cabrero, Monica; Jabbour, Elias; Ravandi, Farhad; Bohannan, Zach; Pierce, Sherry; Kantarjian, Hagop M.; Garcia-Manero, Guillermo

    2016-01-01

    Hypomethylating agents (HMA), such as 5-azacitidine or decitabine, are currently used to treat patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) until treatment failure. However, the outcomes for patients who discontinue therapy after achieving partial response (PR) or complete remission (CR) but before treatment failure have not been reported. We present a series of 16 patients with higher-risk MDS (n=5; 31%) or AML (n=11; 69%) who achieved PR (n=1) or CR (n=15) and stopped HMA therapy while in response in the context of clinical trials. They received a median of 12 courses (range 1–24) and achieved response after a median of 1 course of therapy (1–4). Loss of response after discontinuation of therapy was rapid, with a median progression-free survival of 4 months (95% CI: 2–6). Median overall survival (OS) from the time of therapy discontinuation was 15 months (95% CI: 6–24). Patients who received 12 cycles of therapy or more had significantly better OS (median: 20 months [95% CI: 12–27]) than those who received fewer than 12 cycles (median: 4 months [95% CI: 1–8]) (p= 0.043). Poor-risk cytogenetics were also associated with lower 1-year OS (33% versus 69%; p= 0.046). According to these results and considering the poor prognosis after HMA failure, HMA interruption should be avoided once a sustained response has been achieved. PMID:25828745

  2. Long-term RNA persistence in postmortem contexts

    PubMed Central

    2013-01-01

    Ribonucleic acids (RNA) are generally considered fragile molecules that are readily degraded. However, there is growing documentation of long-term (from days to centuries) RNA persistence in a variety of contexts and tissue types, and as such a number of academic disciplines are beginning to exploit degraded RNA. While the reasons for its survival are not fully understood, there are several plausible mechanisms that would safeguard this molecule against degradation. However, after examining the literature available on the postmortem instability and decay mechanisms of RNA, it has become clear that limited experimental studies and no reviews offer an overview of these mechanisms. Hence in this review we outline molecular reasons for RNA surviving long-term postmortem, and provide specific examples of RNA survival in forensic, archival and archaeological contexts. A better understanding of the mechanisms of RNA decay will be crucial for developing expectations on its long-term survival. PMID:23618361

  3. Subtyping of Breast Cancer by Immunohistochemistry to Investigate a Relationship between Subtype and Short and Long Term Survival: A Collaborative Analysis of Data for 10,159 Cases from 12 Studies

    PubMed Central

    Schmidt, Marjanka K.; Broeks, Annegien; van Leeuwen, Flora E.; Wesseling, Jelle; Cheang, Maggie C.; Gelmon, Karen; Nielsen, Torsten O.; Blomqvist, Carl; Heikkilä, Päivi; Heikkinen, Tuomas; Nevanlinna, Heli; Akslen, Lars A.; Bégin, Louis R.; Foulkes, William D.; Couch, Fergus J.; Wang, Xianshu; Cafourek, Vicky; Olson, Janet E.; Baglietto, Laura; Giles, Graham G.; Severi, Gianluca; McLean, Catriona A.; Southey, Melissa C.; Rakha, Emad; Green, Andrew R.; Ellis, Ian O.; Sherman, Mark E.; Lissowska, Jolanta; Anderson, William F.; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Provenzano, Elena; Dawson, Sarah-Jane; Dunning, Alison M.; Humphreys, Manjeet; Easton, Douglas F.; García-Closas, Montserrat; Caldas, Carlos; Pharoah, Paul D.; Huntsman, David

    2010-01-01

    Background Immunohistochemical markers are often used to classify breast cancer into subtypes that are biologically distinct and behave differently. The aim of this study was to estimate mortality for patients with the major subtypes of breast cancer as classified using five immunohistochemical markers, to investigate patterns of mortality over time, and to test for heterogeneity by subtype. Methods and Findings We pooled data from more than 10,000 cases of invasive breast cancer from 12 studies that had collected information on hormone receptor status, human epidermal growth factor receptor-2 (HER2) status, and at least one basal marker (cytokeratin [CK]5/6 or epidermal growth factor receptor [EGFR]) together with survival time data. Tumours were classified as luminal and nonluminal tumours according to hormone receptor expression. These two groups were further subdivided according to expression of HER2, and finally, the luminal and nonluminal HER2-negative tumours were categorised according to expression of basal markers. Changes in mortality rates over time differed by subtype. In women with luminal HER2-negative subtypes, mortality rates were constant over time, whereas mortality rates associated with the luminal HER2-positive and nonluminal subtypes tended to peak within 5 y of diagnosis and then decline over time. In the first 5 y after diagnosis the nonluminal tumours were associated with a poorer prognosis, but over longer follow-up times the prognosis was poorer in the luminal subtypes, with the worst prognosis at 15 y being in the luminal HER2-positive tumours. Basal marker expression distinguished the HER2-negative luminal and nonluminal tumours into different subtypes. These patterns were independent of any systemic adjuvant therapy. Conclusions The six subtypes of breast cancer defined by expression of five markers show distinct behaviours with important differences in short term and long term prognosis. Application of these markers in the clinical

  4. Interlaboratory evaluation of Hyalella azteca and Chironomus tentans short-term and long-term sediment toxicity tests

    USGS Publications Warehouse

    Norberg-King, T. J.; Sibley, P.K.; Burton, G.A.; Ingersoll, C.G.; Kemble, N.E.; Ireland, S.; Mount, D.R.; Rowland, C.D.

    2006-01-01

    Methods for assessing the long-term toxicity of sediments to Hyalella azteca and Chironomus tentans can significantly enhance the capacity to assess sublethal effects of contaminated sediments through multiple endpoints. Sublethal tests allow us to begin to understand the relationship between short-term and long-term effects for toxic sediments. We present an interlaboratory evaluation with long-term and 10-d tests using control and contaminated sediments in which we assess whether proposed and existing performance criteria (test acceptability criteria [TAC]) could be achieved. Laboratories became familiar with newly developed, long-term protocols by testing two control sediments in phase 1. In phase 2, the 10-d and long-term tests were examined with several sediments. Laboratories met the TACs, but results varied depending on the test organism, test duration, and endpoints. For the long-term tests in phase 1, 66 to 100% of the laboratories consistently met the TACs for survival, growth, or reproduction using H. azteca, and 70 to 100% of the laboratories met the TACs for survival and growth, emergence, reproduction, and hatchability using C. tentans. In phase 2, fewer laboratories participated in long-term tests: 71 to 88% of the laboratories met the TAC for H. azteca, whereas 50 to 67% met the TAC for C. tentans. In the 10-d tests with H. azteca and C. tentans, 82 and 88% of the laboratories met the TAC for survival, respectively, and 80% met the TAC for C. tentans growth. For the 10-d and long-term tests, laboratories predicted similar toxicity. Overall, the interlaboratory evaluation showed good precision of the methods, appropriate endpoints were incorporated into the test protocols, and tests effectively predicted the toxicity of sediments. ?? 2006 SETAC.

  5. Long-Term Effects of an Early Childhood Intervention on Educational Achievement and Juvenile Arrest: A 15-Year Follow-Up of Low-Income Children in Public Schools.

    ERIC Educational Resources Information Center

    Reynolds, Arthur J.; Temple, Judy A.; Robertson, Dylan L.; Mann, Emily A.

    2001-01-01

    Examined long-term effectiveness of the Chicago Child-Parent Center program on rates of high school completion and school dropout by age 20. Found that, compared to nonparticipants and adjusted for covariates, preschool participants had higher rate of high school completion, more years of education, and lower juvenile arrest and violent crime…

  6. Craniopharyngioma in Children: Long-term Outcomes

    PubMed Central

    STEINBOK, Paul

    2015-01-01

    The survival rate for childhood craniopharyngioma has been improving, with more long-term survivors. Unfortunately it is rare for the patient to be normal, either from the disease itself or from the effects of treatment. Long-term survivors of childhood craniopharyngioma suffer a number of impairments, which include visual loss, endocrinopathy, hypothalamic dysfunction, cerebrovascular problems, neurologic and neurocognitive dysfunction. Pituitary insufficiency is present in almost 100%. Visual and hypothalamic dysfunction is common. There is a high risk of metabolic syndrome and increased risk of cerebrovascular disease, including stroke and Moyamoya syndrome. Cognitive, psychosocial, and emotional problems are prevalent. Finally, there is a higher risk of premature death among survivors of craniopharyngioma, and often this is not from tumor recurrence. It is important to consider craniopharyngioma as a chronic disease. There is no perfect treatment. The treatment has to be tailored to the individual patient to minimize dysfunction caused by tumor and treatments. So “cure” of the tumor does not mean a normal patient. The management of the patient and family needs multidisciplinary evaluation and should involve ophthalmology, endocrinology, neurosurgery, oncology, and psychology. Furthermore, it is also important to address emotional issues and social integration. PMID:26345668

  7. Viability of long-term gene therapy in the cochlea.

    PubMed

    Atkinson, Patrick J; Wise, Andrew K; Flynn, Brianna O; Nayagam, Bryony A; Richardson, Rachael T

    2014-04-22

    Gene therapy has been investigated as a way to introduce a variety of genes to treat neurological disorders. An important clinical consideration is its long-term effectiveness. This research aims to study the long-term expression and effectiveness of gene therapy in promoting spiral ganglion neuron survival after deafness. Adenoviral vectors modified to express brain derived neurotrophic factor or neurotrophin-3 were unilaterally injected into the guinea pig cochlea one week post ototoxic deafening. After six months, persistence of gene expression and significantly greater neuronal survival in neurotrophin-treated cochleae compared to the contralateral cochleae were observed. The long-term gene expression observed indicates that gene therapy is potentially viable; however the degeneration of the transduced cells as a result of the original ototoxic insult may limit clinical effectiveness. With further research aimed at transducing stable cochlear cells, gene therapy may be an efficacious way to introduce neurotrophins to promote neuronal survival after hearing loss.

  8. Low nonrelapse mortality and prolonged long-term survival after reduced-intensity allogeneic stem cell transplantation for relapsed or refractory diffuse large B cell lymphoma: report of the Société Française de Greffe de Moelle et de Thérapie Cellulaire.

    PubMed

    Sirvent, Anne; Dhedin, Nathalie; Michallet, Mauricette; Mounier, Nicolas; Faucher, Catherine; Yakoub-Agha, Ibrahim; Mohty, Mohamad; Robin, Marie; Tabrizi, Reza; Clement, Laurence; Bilger, Karin; Larosa, Fabrice; Contentin, Nathalie; Huyn, Anne; François, Sylvie; Bulabois, Claude-Eric; Ceballos, Patrice; Bourrhis, Jean-Henri; Buzyn, Agnès; Cornillon, Jérôme; Guillerm, Gaelle; de Revel, Thierry; Bay, Jacques-Olivier; Guilhot, François; Milpied, Noël

    2010-01-01

    Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) have a very poor prognosis. However, they may achieve long-term survival by undergoing allogeneic stem cell transplantation (SCT). The purpose of this study was to assess the outcome of all adult patients with DLBCL whose treatment included a reduced-intensity conditioning (RIC) regimen for allogeneic SCT and whose data were reported in the French Society of Marrow Transplantation and Cellular Therapy registry. Sixty-eight patients (median age: 48 years) were transplanted from October 1998 to January 2007. They had received a median of 2 regimens of therapy prior to allogeneic SCT, and 54 (79%) had already undergone SCT. Prior to transplantation, 32 patients (47%) were in complete remission (CR). For all patients but 1, conditioning regimens were based on fludarabine (Flu), which was combined with other chemotherapy drugs in 50 cases (74%) and with total body irradiation (TBI) in 17 (25%). For 56 patients (82%), the donor was an HLA-matched sibling, and peripheral blood was the most widely used source of stem cells (57 patients, 84%). With a median follow-up of 49 months, estimated 2-year overall survival (OS), progression-free survival (PFS), and the cumulative incidence of relapse were 49%, 44%, and 41%, respectively. The 1-year cumulative incidence of nonrelapse mortality (NRM) was 23%. According to multivariate analysis, the patients in CR before transplantation had a significantly longer PFS and a lower CI of relapse than patients transplanted during partial remission or stable or progressive disease. These results suggest that reduced-intensity allergenic transplantation is an attractive therapeutic option for patients with high-risk DLBCL.

  9. Long-term outcomes of urinary tract reconstruction in patients with neurogenic urinary tract dysfunction.

    PubMed

    Johnson, E U; Singh, Gurpreet

    2013-10-01

    The advent of specialized spinal units and better understanding of the pathophysiology of neurogenic urinary tract dysfunction has made long-term survival of these patients a reality. This has, in turn, led to an increase in quality and choice of management modalities offered to these patients including complex anatomic urinary tract reconstructive procedures tailored to the unique needs of each individual with variable outcomes. We performed a literature review evaluating the long-term outcomes of these reconstructive procedures. To achieve this, we conducted a world-wide electronic literature search of long-term outcomes published in English. As the premise of this review is long-term outcomes, we have focused on pathologies where evidence of long-term outcome is available such as patients with spinal injuries and spina bifida. Therapeutic success following urinary tract reconstruction is usually measured by preservation of renal function, improvement in quality-of-life, the satisfactory achievement of agreed outcomes and the prevention of serious complications. Prognostic factors include neuropathic detrusor overactivity; sphincter dyssynergia; bladder over distension; high pressure storage and high leak point pressures; vesicoureteric reflex, stone formation and urinary tract infections. Although, the past decade has witnessed a reduction in the total number of bladder reconstructive surgeries in the UK, these procedures are essentially safe and effective; but require long-term clinical and functional follow-up/monitoring. Until tissue engineering and gene therapy becomes more mainstream, we feel there is still a place for urinary tract reconstruction in patients with neurogenic lower urinary tract dysfunction.

  10. Long-term outcomes of urinary tract reconstruction in patients with neurogenic urinary tract dysfunction

    PubMed Central

    Johnson, E. U.; Singh, Gurpreet

    2013-01-01

    The advent of specialized spinal units and better understanding of the pathophysiology of neurogenic urinary tract dysfunction has made long-term survival of these patients a reality. This has, in turn, led to an increase in quality and choice of management modalities offered to these patients including complex anatomic urinary tract reconstructive procedures tailored to the unique needs of each individual with variable outcomes. We performed a literature review evaluating the long-term outcomes of these reconstructive procedures. To achieve this, we conducted a world-wide electronic literature search of long-term outcomes published in English. As the premise of this review is long-term outcomes, we have focused on pathologies where evidence of long-term outcome is available such as patients with spinal injuries and spina bifida. Therapeutic success following urinary tract reconstruction is usually measured by preservation of renal function, improvement in quality-of-life, the satisfactory achievement of agreed outcomes and the prevention of serious complications. Prognostic factors include neuropathic detrusor overactivity; sphincter dyssynergia; bladder over distension; high pressure storage and high leak point pressures; vesicoureteric reflex, stone formation and urinary tract infections. Although, the past decade has witnessed a reduction in the total number of bladder reconstructive surgeries in the UK, these procedures are essentially safe and effective; but require long-term clinical and functional follow-up/monitoring. Until tissue engineering and gene therapy becomes more mainstream, we feel there is still a place for urinary tract reconstruction in patients with neurogenic lower urinary tract dysfunction. PMID:24235796

  11. [Childhood liver transplantation. Long-term results].

    PubMed

    Jara, Paloma; Hierro, Loreto

    2010-05-01

    Liver transplantation allows long-term survival (10 years or more) in 75% of children receiving transplants before 2000. The risk of mortality after the first year is 4-10% in the next 10-20 years. Chronic rejection affects 6%. The need for late retransplantation is 3-5%. However, the follow-up of these patients involves the management of diverse problems in the graft (immunological, biliary, vascular) and others related to the use of immunosuppressants (renal dysfunction, lymphoproliferative syndrome). The transition from pediatric to adult care generates special needs. Adolescence and young adulthood are associated with a lack of compliance. Adult specialists should be aware of the special features of the original diagnosis and the surgical techniques used in childhood transplantation. Final quality of life is good overall but is lower than that in healthy young persons.

  12. Asthma Medicines: Long-Term Control

    MedlinePlus

    ... Size Email Print Share Asthma Medicines: Long-term Control Page Content Article Body Corticosteroids Synthetic versions of ... form, they are used exclusively for long-term control; they are not very effective for acute symptoms. ...

  13. Long Term Surface Salinity Measurements

    NASA Technical Reports Server (NTRS)

    Schmitt, Raymond W.; Brown, Neil L.

    2005-01-01

    Our long-term goal is to establish a reliable system for monitoring surface salinity around the global ocean. Salinity is a strong indicator of the freshwater cycle and has a great influence on upper ocean stratification. Global salinity measurements have potential to improve climate forecasts if an observation system can be developed. This project is developing a new internal field conductivity cell that can be protected from biological fouling for two years. Combined with a temperature sensor, this foul-proof cell can be deployed widely on surface drifters. A reliable in-situ network of surface salinity sensors will be an important adjunct to the salinity sensing satellite AQUARIUS to be deployed by NASA in 2009. A new internal-field conductivity cell has been developed by N Brown, along with new electronics. This sensor system has been combined with a temperature sensor to make a conductivity - temperature (UT) sensor suitable for deployment on drifters. The basic sensor concepts have been proven on a high resolution CTD. A simpler (lower cost) circuit has been built for this application. A protection mechanism for the conductivity cell that includes antifouling protection has also been designed and built. Mr. A.Walsh of our commercial partner E-Paint has designed and delivered time-release formulations of antifoulants for our application. Mr. G. Williams of partner Clearwater Instrumentation advised on power and communication issues and supplied surface drifters for testing.

  14. Long-Term Planning in Higher Education.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific and Cultural Organization, Bangkok (Thailand). Principal Regional Office for Asia and the Pacific.

    This report presents the concepts and issues discussed at a Regional Symposium on Long-term Planning in Higher Education held in Dhaka, Bangladesh, September 21-30, 1986. Chapter 1 explores some fundamental issues about the rationale for the objectives of long-term planning. It defines long-term planning in higher education, considers its…

  15. Long Term TOA - M Data and Information

    Atmospheric Science Data Center

    2015-06-30

    A Long-Term TOA and Constrained Surface Radiation Budget Project A Long-Term TOA and Constrained Surface Readiation Budget Dataset Using Merged CERES, ... and apply the knowledge to existing data to develop long-term (nearly 30 years) consistent and calibrated data product (TOA irradiances ...

  16. Long-term Ecological Monitoring in Schools and Colleges.

    ERIC Educational Resources Information Center

    Doberski, Julian; Brodie, Iain D. S.

    1991-01-01

    The value and difficulties of long-term ecological monitoring studies undertaken in schools and colleges are reviewed. Rookeries, stream ecology, sand dune succession, fish population, and seed production and survival are presented as examples of successful studies. This is followed by a discussion of points to consider when setting up a long-term…

  17. Skeletal muscle tissue engineering: a maturation model promoting long-term survival of myotubes, structural development of the excitation-contraction coupling apparatus and neonatal myosin heavy chain expression.

    PubMed

    Das, Mainak; Rumsey, John W; Bhargava, Neelima; Stancescu, Maria; Hickman, James J

    2009-10-01

    The use of defined in vitro systems to study the developmental and physiological characteristics of a variety of cell types is increasing, due in large part to their ease of integration with tissue engineering, regenerative medicine, and high-throughput screening applications. In this study, myotubes derived from fetal rat hind limbs were induced to develop several aspects of mature muscle including: sarcomere assembly, development of the excitation-contraction coupling apparatus and myosin heavy chain (MHC) class switching. Utilizing immunocytochemical analysis, anisotropic and isotropic band formation (striations) within the myotubes was established, indicative of sarcomere formation. In addition, clusters of ryanodine receptors were colocalized with dihydropyridine complex proteins which signaled development of the excitation-contraction coupling apparatus and transverse tubule biogenesis. The myotubes also exhibited MHC class switching from embryonic to neonatal MHC. Lastly, the myotubes survived significantly longer in culture (70-90 days) than myotubes from our previously developed system (20-25 days). These results were achieved by modifying the culture timeline as well as the development of a new medium formulation. This defined model system for skeletal muscle maturation supports the goal of developing physiologically relevant muscle constructs for use in tissue engineering and regenerative medicine as well as for high-throughput screening applications.

  18. The Long-Term Effects of Remedial Reading Instruction.

    ERIC Educational Resources Information Center

    Brightbill, Mary

    The long-term effects (after 3 to 5 years) of remedial reading instruction were examined. Comparison was made on reading achievement scores and on achievement ratios between a group of 16 former remedial reading clinic students, aged 12 to 20, and a matched group which did not receive remedial instruction. In addition, 45 former remedial readers…

  19. 43 CFR 3904.40 - Long-term water treatment trust funds.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Long-term water treatment trust funds... Bonds and Trust Funds § 3904.40 Long-term water treatment trust funds. (a) The BLM may require the...-term treatment to achieve water quality standards and for other long-term, post-mining...

  20. 43 CFR 3904.40 - Long-term water treatment trust funds.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Long-term water treatment trust funds...-GENERAL Bonds and Trust Funds § 3904.40 Long-term water treatment trust funds. (a) The BLM may require the...-term treatment to achieve water quality standards and for other long-term, post-mining...

  1. 43 CFR 3904.40 - Long-term water treatment trust funds.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Long-term water treatment trust funds...-GENERAL Bonds and Trust Funds § 3904.40 Long-term water treatment trust funds. (a) The BLM may require the...-term treatment to achieve water quality standards and for other long-term, post-mining...

  2. 43 CFR 3904.40 - Long-term water treatment trust funds.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Long-term water treatment trust funds...-GENERAL Bonds and Trust Funds § 3904.40 Long-term water treatment trust funds. (a) The BLM may require the...-term treatment to achieve water quality standards and for other long-term, post-mining...

  3. Hispanic Cultural Survival and Academic Achievement: A Partnership That Works.

    ERIC Educational Resources Information Center

    Rivera, Manuel G.

    The life of Benito Juarez--who broke all odds to achieve academically, politically, and socially--serves proof that Hispanics can achieve without sacrificing their cultural heritage. The current educational achievement of Hispanics in California and elsewhere in the nation is a matter for serious consideration. Nearly 50% of all Hispanics enrolled…

  4. Long-term solar-terrestrial observations

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The results of an 18-month study of the requirements for long-term monitoring and archiving of solar-terrestrial data is presented. The value of long-term solar-terrestrial observations is discussed together with parameters, associated measurements, and observational problem areas in each of the solar-terrestrial links (the sun, the interplanetary medium, the magnetosphere, and the thermosphere-ionosphere). Some recommendations are offered for coordinated planning for long-term solar-terrestrial observations.

  5. Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment

    PubMed Central

    Horwitz, Mitchell E.; Chao, Nelson J.; Rizzieri, David A.; Long, Gwynn D.; Sullivan, Keith M.; Gasparetto, Cristina; Chute, John P.; Morris, Ashley; McDonald, Carolyn; Waters-Pick, Barbara; Stiff, Patrick; Wease, Steven; Peled, Amnon; Snyder, David; Cohen, Einat Galamidi; Shoham, Hadas; Landau, Efrat; Friend, Etty; Peleg, Iddo; Aschengrau, Dorit; Yackoubov, Dima; Kurtzberg, Joanne; Peled, Tony

    2014-01-01

    BACKGROUND. Delayed hematopoietic recovery is a major drawback of umbilical cord blood (UCB) transplantation. Transplantation of ex vivo–expanded UCB shortens time to hematopoietic recovery, but long-term, robust engraftment by the expanded unit has yet to be demonstrated. We tested the hypothesis that a UCB-derived cell product consisting of stem cells expanded for 21 days in the presence of nicotinamide and a noncultured T cell fraction (NiCord) can accelerate hematopoietic recovery and provide long-term engraftment. METHODS. In a phase I trial, 11 adults with hematologic malignancies received myeloablative bone marrow conditioning followed by transplantation with NiCord and a second unmanipulated UCB unit. Safety, hematopoietic recovery, and donor engraftment were assessed and compared with historical controls. RESULTS. No adverse events were attributable to the infusion of NiCord. Complete or partial neutrophil and T cell engraftment derived from NiCord was observed in 8 patients, and NiCord engraftment remained stable in all patients, with a median follow-up of 21 months. Two patients achieved long-term engraftment with the unmanipulated unit. Patients transplanted with NiCord achieved earlier median neutrophil recovery (13 vs. 25 days, P < 0.001) compared with that seen in historical controls. The 1-year overall and progression-free survival rates were 82% and 73%, respectively. CONCLUSION. UCB-derived hematopoietic stem and progenitor cells expanded in the presence of nicotinamide and transplanted with a T cell–containing fraction contain both short-term and long-term repopulating cells. The results justify further study of NiCord transplantation as a single UCB graft. If long-term safety is confirmed, NiCord has the potential to broaden accessibility and reduce the toxicity of UCB transplantation. TRIAL REGISTRATION. Clinicaltrials.gov NCT01221857. FUNDING. Gamida Cell Ltd. PMID:24911148

  6. Managing soils for long-term productivity

    PubMed Central

    Syers, J. K.

    1997-01-01

    erosion accentuates the often very low inherent fertility of many soils in the tropics. An integrated approach involving inorganic and organic inputs is required where animal and plant residues are returned, as far as practicable. Chemical fertilizers alone cannot achieve long-term productivity on many soils and organic material inputs are required to maintain soil organic matter levels and crop productivity. A major research effort is required to develop improved strategies for halting and reversing soil degradation if long-term productivity is to be secured.

  7. Human sperm chromosomes. Long-term effect of cancer treatment

    SciTech Connect

    Genesca, A.; Caballin, M.R.; Miro, R.; Benet, J.; Bonfill, X.; Egozcue, J. )

    1990-06-01

    The long-term cytogenetic effect of radio- or chemotherapy or both on male germ cells was evaluated by study of the chromosomal abnormalities in spermatozoa of four men treated for cancer 5-18 years earlier. The cytogenetic analysis of 422 sperm metaphases showed no differences in the aneuploidy rate. The incidence of structural chromosome aberrations was 14.0%, however, which is much higher than in controls. Thus, the high incidence of structurally aberrant spermatozoa observed in our long-term study indicates that antitumoral treatments affect stem-cell spermatogonia and that aberrant cells can survive germinal selection and produce abnormal spermatozoa.

  8. LIMS for Lasers 2015 for achieving long-term accuracy and precision of δ2H, δ17O, and δ18O of waters using laser absorption spectrometry

    USGS Publications Warehouse

    Coplen, Tyler B.; Wassenaar, Leonard I

    2015-01-01

    Although laser absorption spectrometry (LAS) instrumentation is easy to use, its incorporation into laboratory operations is not easy, owing to extensive offline manipulation of comma-separated-values files for outlier detection, between-sample memory correction, nonlinearity (δ-variation with water amount) correction, drift correction, normalization to VSMOW-SLAP scales, and difficulty in performing long-term QA/QC audits. METHODS: A Microsoft Access relational-database application, LIMS (Laboratory Information Management System) for Lasers 2015, was developed. It automates LAS data corrections and manages clients, projects, samples, instrument-sample lists, and triple-isotope (δ(17) O, δ(18) O, and δ(2) H values) instrumental data for liquid-water samples. It enables users to (1) graphically evaluate sample injections for variable water yields and high isotope-delta variance; (2) correct for between-sample carryover, instrumental drift, and δ nonlinearity; and (3) normalize final results to VSMOW-SLAP scales. RESULTS: Cost-free LIMS for Lasers 2015 enables users to obtain improved δ(17) O, δ(18) O, and δ(2) H values with liquid-water LAS instruments, even those with under-performing syringes. For example, LAS δ(2) HVSMOW measurements of USGS50 Lake Kyoga (Uganda) water using an under-performing syringe having ±10 % variation in water concentration gave +31.7 ± 1.6 ‰ (2-σ standard deviation), compared with the reference value of +32.8 ± 0.4 ‰, after correction for variation in δ value with water concentration, between-sample memory, and normalization to the VSMOW-SLAP scale. CONCLUSIONS: LIMS for Lasers 2015 enables users to create systematic, well-founded instrument templates, import δ(2) H, δ(17) O, and δ(18) O results, evaluate performance with automatic graphical plots, correct for δ nonlinearity due to variable water concentration, correct for between-sample memory, adjust for drift, perform VSMOW-SLAP normalization, and

  9. LIMS for Lasers 2015 for achieving long-term accuracy and precision of δ2H, δ17O, and δ18O of waters using laser absorption spectrometry

    USGS Publications Warehouse

    Coplen, Tyler B.; Wassenaar, Leonard I

    2015-01-01

    RationaleAlthough laser absorption spectrometry (LAS) instrumentation is easy to use, its incorporation into laboratory operations is not easy, owing to extensive offline manipulation of comma-separated-values files for outlier detection, between-sample memory correction, nonlinearity (δ-variation with water amount) correction, drift correction, normalization to VSMOW-SLAP scales, and difficulty in performing long-term QA/QC audits.MethodsA Microsoft Access relational-database application, LIMS (Laboratory Information Management System) for Lasers 2015, was developed. It automates LAS data corrections and manages clients, projects, samples, instrument-sample lists, and triple-isotope (δ17O, δ18O, and δ2H values) instrumental data for liquid-water samples. It enables users to (1) graphically evaluate sample injections for variable water yields and high isotope-delta variance; (2) correct for between-sample carryover, instrumental drift, and δ nonlinearity; and (3) normalize final results to VSMOW-SLAP scales.ResultsCost-free LIMS for Lasers 2015 enables users to obtain improved δ17O, δ18O, and δ2H values with liquid-water LAS instruments, even those with under-performing syringes. For example, LAS δ2HVSMOW measurements of USGS50 Lake Kyoga (Uganda) water using an under-performing syringe having ±10 % variation in water concentration gave +31.7 ± 1.6 ‰ (2-σ standard deviation), compared with the reference value of +32.8 ± 0.4 ‰, after correction for variation in δ value with water concentration, between-sample memory, and normalization to the VSMOW-SLAP scale.ConclusionsLIMS for Lasers 2015 enables users to create systematic, well-founded instrument templates, import δ2H, δ17O, and δ18O results, evaluate performance with automatic graphical plots, correct for δ nonlinearity due to variable water concentration, correct for between-sample memory, adjust for drift, perform VSMOW-SLAP normalization, and perform long-term QA/QC audits

  10. Long-term effects of nanoparticles on nutrition and metabolism.

    PubMed

    Chen, Nan; Wang, Hui; Huang, Qing; Li, Jiang; Yan, Juan; He, Dannong; Fan, Chunhai; Song, Haiyun

    2014-09-24

    Nanoparticles have shown great potential in biological and biomedical applications due to their distinct physical and chemical properties. In the meanwhile, the biosafety of nanoparticles has also raised intense concerns worldwide. To address such concerns, great efforts have been made to examine short-term effects of nanoparticles on cell survival and proliferation. More recently, exploration of long-term effects of nanomaterials, particularly those with promising biomedical applications in vivo, has aroused significant interest. For example, gold nanoparticles (AuNPs) are generally considered non-toxic to cell growth, whereas recent studies suggest that AuNPs might have long-term effects on cellular metabolism and energy homeostasis. In this Review, recent advances in this direction are summarized. Further, possible mechanisms under which nanoparticles regulate metabolic signaling pathways, potential long-term effects on cellular anabolic or catabolic processes, and their implications in human health and metabolic disorders are discussed.

  11. Short and Long-Term Outcomes for Extremely Preterm Infants

    PubMed Central

    Patel, Ravi Mangal

    2016-01-01

    Prematurity is the leading cause of infant mortality worldwide. In developed countries, extremely preterm infants contribute disproportionately to both neonatal and infant mortality. Survival of this high-risk population has incrementally improved in recent years. Despite these improvements, approximately 1 in 4 extremely preterm infants dies during the birth hospitalization. Among those who survive, respiratory and other morbidities are common, although their effect on quality of life is variable. In addition, long-term neurodevelopmental impairment is a large concern for patients, clinicians and families. However, the interplay of multiple factors contribute to neurodevelopmental impairment, with measures that change over time and outcomes that can be difficult to define and predict. Understanding outcomes of extremely preterm infants can help better counsel families regarding antenatal and postnatal care and guide strategies to improve survival without morbidity. This review summarizes recent evidence to provide an overview into the short- and long-term outcomes for extremely preterm infants. PMID:26799967

  12. Virtual Models of Long-Term Care

    ERIC Educational Resources Information Center

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

    Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

  13. Long-Term Nutrition: A Clinician's Guide to Successful Long-Term Enteral Access in Adults.

    PubMed

    Bechtold, Matthew L; Mir, Fazia A; Boumitri, Christine; Palmer, Lena B; Evans, David C; Kiraly, Laszlo N; Nguyen, Douglas L

    2016-09-22

    Long-term nutrition support requires long-term enteral access. To ensure the success of long-term enteral access, many factors need to be taken into consideration. This article represents a guide to placing and maintaining access in patients requiring long-term nutrition and addresses many of the common questions regarding long-term enteral access, such as indications, types of access, feeding after access placed, and recognition and treatment of potential complications. This guide will help the clinician establish and maintain access to maximize nutrition in patients requiring long-term nutrition.

  14. Paying for long-term care.

    PubMed Central

    Estes, C L; Bodenheimer, T

    1994-01-01

    Everyone agrees that insurance for long-term care is inadequate in the United States. Disagreement exists, however, on whether such insurance should be provided through the private or public sector. Private insurance generally uses the experience-rating principle that persons with higher risk of illness are charged higher premiums. For private insurance for long-term care, this principle creates a dilemma. Most policies will be purchased by the elderly; yet, because the elderly have a high risk of needing long-term care, only about 20% of them can afford the cost of premiums. A public-private partnership by which the government partially subsidizes private long-term-care insurance is unlikely to resolve this dilemma. Only a social insurance program for long-term care can provide universal, affordable, and equitable coverage. PMID:8128712

  15. Natural History of Cardiac and Respiratory Involvement, Prognosis and Predictive Factors for Long-Term Survival in Adult Patients with Limb Girdle Muscular Dystrophies Type 2C and 2D

    PubMed Central

    Fayssoil, Abdallah; Ogna, Adam; Chaffaut, Cendrine; Chevret, Sylvie; Guimarães-Costa, Raquel; Leturcq, France; Wahbi, Karim; Prigent, Helene; Lofaso, Frederic; Nardi, Olivier; Clair, Bernard; Behin, Anthony; Stojkovic, Tanya; Laforet, Pascal; Orlikowski, David; Annane, Djillali

    2016-01-01

    Background Type 2C and 2D limb girdle muscular dystrophies (LGMD) are a group of autosomal recessive limb girdle muscular dystrophies manifested by proximal myopathy, impaired respiratory muscle function and cardiomyopathy. The correlation and the prognostic impact of respiratory and heart impairment are poorly described. We aimed to describe the long-term cardiac and respiratory follow-up of these patients and to determine predictive factors of cardio-respiratory events and mortality in LGMD 2C and 2D. Methods We reviewed the charts of 34 LGMD patients, followed from 2005 to 2015, to obtain echocardiographic, respiratory function and sleep recording data. We considered respiratory events (acute respiratory failure, pulmonary sepsis, atelectasis or pneumothorax), cardiac events (acute heart failure, significant cardiac arrhythmia or conduction block, ischemic stroke) and mortality as outcomes of interest for the present analysis. Results A total of 21 patients had type 2C LGMD and 13 patients had type 2D. Median age was 30 years [IQR 24–38]. At baseline, median pulmonary vital capacity (VC) was 31% of predicted value [20–40]. Median maximal inspiratory pressure (MIP) was 31 cmH2O [IQR 20.25–39.75]. Median maximal expiratory pressure (MEP) was 30 cm H2O [20–36]. Median left ventricular ejection fraction (LVEF) was 55% [45–64] with 38% of patients with LVEF <50%. Over a median follow-up of 6 years, we observed 38% respiratory events, 14% cardiac events and 20% mortality. Among baseline characteristics, LVEF and left ventricular end diastolic diameter (LVEDD) were associated with mortality, whilst respiratory parameters (VC, MIP, MEP) and the need for home mechanical ventilation (HMV) were associated with respiratory events. Conclusion In our cohort of severely respiratory impaired type 2C and 2D LGMD, respiratory morbidity was high. Cardiac dysfunction was frequent in particular in LGMD 2C and had an impact on long-term mortality. Trial Registration

  16. LONG-TERM MONITORING SENSOR NETWORK

    SciTech Connect

    Stephen P. Farrington; John W. Haas; Neal Van Wyck

    2003-10-16

    Long-term monitoring (LTM) associated with subsurface contamination sites is a key element of Long Term Stewardship and Legacy Management across the Department of Energy (DOE) complex. However, both within the DOE and elsewhere, LTM is an expensive endeavor, often exceeding the costs of the remediation phase of a clean-up project. The primary contributors to LTM costs are associated with labor. Sample collection, storage, preparation, analysis, and reporting can add a significant financial burden to project expense when extended over many years. Development of unattended, in situ monitoring networks capable of providing quantitative data satisfactory to regulatory concerns has the potential to significantly reduce LTM costs. But survival and dependable operation in a difficult environment is a common obstacle to widespread use across the DOE complex or elsewhere. Deploying almost any sensor in the subsurface for extended periods of time will expose it to chemical and microbial degradation. Over the time-scales required for in situ LTM, even the most advanced sensor systems may be rendered useless. Frequent replacement or servicing (cleaning) of sensors is expensive and labor intensive, offsetting most, if not all, of the cost savings realized with unattended, in situ sensors. To enable facile, remote monitoring of contaminants and other subsurface parameters over prolonged periods, Applied Research Associates, Inc has been working to develop an advanced LTM sensor network consisting of three key elements: (1) an anti-fouling sensor chamber that can accommodate a variety of chemical and physical measurement devices based on electrochemical, optical and other techniques; (2) two rapid, cost effective, and gentle means of emplacing sensor packages either at precise locations directly in the subsurface or in pre-existing monitoring wells; and (3) a web browser-based data acquisition and control system (WebDACS) utilizing field-networked microprocessor-controlled smart

  17. Modulation of axonal sprouting along rostro-caudal axis of dorsal hippocampus and no neuronal survival in parahippocampal cortices by long-term post-lesion melatonin administration in lithium-pilocarpine model of temporal lobe epilepsy

    PubMed Central

    Ganjkhani, Mahin; Ali, Rostami; Iraj, Jafari Anarkooli

    2016-01-01

    Feature outcome of hippocampus and extra-hippocampal cortices was evaluated in melatonin treated lithium-pilocarpine epileptic rats during early and chronic phases of temporal lobe epilepsy (TLE). After status epilepticus (SE) induction, 5 and 20 mg/kg melatonin were administered for 14 days or 60 days. All animals were killed 60 days post SE induction and the histological features of the rosrto-caudal axis of the dorsal hippocampus, piriform and entorhinal cortices were evaluated utilizing Nissl, Timm, and synapsin I immunoflorescent staining. Melatonin (20 mg/kg) effect on CA1 and CA3 neurons showed a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus. The number of counted granular cells by melatonin (20 mg/kg) treatment increased along the rostro-caudal axis of the dorsal hippocampus in comparison to the untreated epileptic group. The density of Timm granules in the inner molecular layer of the dentate gyrus decreased significantly in all melatonin treated groups in comparison to the untreated epileptic animals. The increased density of synapsin I immunoreactivity in the outer molecular layer of the dentate gyrus of untreated epileptic rats showed a profound decrease following melatonin treatment. There was no neuronal protection in the piriform and entorhinal cortices whatever the melatonin treatment. Long-term melatonin administration as a co-adjuvant probably could reduce the post-lesion histological consequences of TLE in a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus. PMID:27051565

  18. Exploratory Analyses of the Long-Term Effects of Improving Behavior, Attendance, and Educational Achievement in Grades 1-6 and 8-12. ACT Research Report Series, 2012 (3)

    ERIC Educational Resources Information Center

    Sawyer, Richard; Gibson, Neal

    2012-01-01

    We studied relationships among background characteristics, behavioral infractions, punishments, attendance, and educational achievement, using longitudinal data of students in grades 1-6 and 8-12. We estimated how much hypothesized early improvements in educational achievement or sustained improvements in behavior and attendance might ultimately…

  19. Security basics for long-term care facilities.

    PubMed

    Green, Martin

    2015-01-01

    The need for Long-Term Care (LTC) facilities is growing, the author reports, and along with it the need for programs to address the major security concerns of such facilities. In this article he explains how to apply the IAHSS Healthcare Security Industry Guidelines and the Design Guidelines to achieve a safer LTC facility.

  20. Mathematics Learning Development: The Role of Long-Term Retrieval

    ERIC Educational Resources Information Center

    Calderón-Tena, Carlos O.; Caterino, Linda C.

    2016-01-01

    This study assessed the relation between long-term memory retrieval and mathematics calculation and mathematics problem solving achievement among elementary, middle, and high school students in nationally representative sample of US students, when controlling for fluid and crystallized intelligence, short-term memory, and processing speed. As…

  1. Incidental Biasing of Attention from Visual Long-Term Memory

    ERIC Educational Resources Information Center

    Fan, Judith E.; Turk-Browne, Nicholas B.

    2016-01-01

    Holding recently experienced information in mind can help us achieve our current goals. However, such immediate and direct forms of guidance from working memory are less helpful over extended delays or when other related information in long-term memory is useful for reaching these goals. Here we show that information that was encoded in the past…

  2. Does Head Start Yield Long-Term Benefits?

    ERIC Educational Resources Information Center

    Aughinbaugh, Alison

    2001-01-01

    Using 1997 National Longitudinal Survey of Youth data (n=7,787), the relationship between Head Start and school suspensions, grade repetition, and math achievement was examined. Estimates indicate that Head Start does not have long-term benefits, a finding compatible with studies showing that compensatory preschool programs need to be long in…

  3. Congenital hepatic fibrosis: the long-term prognosis.

    PubMed Central

    Kerr, D N; Okonkwo, S; Choa, R G

    1978-01-01

    The long-term prognosis in congenital hepatic fibrosis has been assessed in 30 patients, 13 treated at Newcastle and 17 from other British centres. Twenty-four patients had been followed-up for more than five years from diagnosis. Shunt operations, performed in 18 patients, were successful in controlling haemorrhage with a low mortality (1/18), low incidence of recurrent haemorrhage (3/18) and portal-systemic encephalopathy (3/18) but with a higher incidence of postoperative jaundice (7/18). About a third of the survivors had some evidence of hepatic dysfunction but none had chronic portal systemic encephalopathy. Intelligence quotient was close to normal but educational achievement and job status were low. Serum albumin fell after shunt surgery and a few patients developed ascites: anaemia and hypersplenism however, were corrected by surgery. Blood ammonia is raised in survivors with congenital hepatic fibrosis and rises further after a normal meal; further observations are needed on cerebral function after several decades of survival. PMID:680586

  4. The Challenge of Long-Term Climate Change

    NASA Astrophysics Data System (ADS)

    Hasselmann, K.; Latif, M.; Hooss, G.; Azar, C.; Edenhofer, O.; Jaeger, C. C.; Johannessen, O. M.; Kemfert, C.; Welp, M.; Wokaun, A.

    2003-12-01

    Climate policy needs to address the multidecadal to centennial time scale of climate change. Although the realization of short-term targets is an important first step, to be effective climate policies need to be conceived as long-term programs that will achieve a gradual transition to an essentially emission-free economy on the time scale of a century. This requires a considerably broader spectrum of policy measures than the primarily market-based instruments invoked for shorter term mitigation policies. A successful climate policy must consist of a dual approach focusing on both short-term targets and long-term goals.

  5. Long-term fate of neural precursor cells following transplantation into developing and adult CNS.

    PubMed

    Lepore, A C; Neuhuber, B; Connors, T M; Han, S S W; Liu, Y; Daniels, M P; Rao, M S; Fischer, I

    2006-05-12

    Successful strategies for transplantation of neural precursor cells for replacement of lost or dysfunctional CNS cells require long-term survival of grafted cells and integration with the host system, potentially for the life of the recipient. It is also important to demonstrate that transplants do not result in adverse outcomes. Few studies have examined the long-term properties of transplanted neural precursor cells in the CNS, particularly in non-neurogenic regions of the adult. The aim of the present study was to extensively characterize the fate of defined populations of neural precursor cells following transplantation into the developing and adult CNS (brain and spinal cord) for up to 15 months, including integration of graft-derived neurons with the host. Specifically, we employed neuronal-restricted precursors and glial-restricted precursors, which represent neural precursor cells with lineage restrictions for neuronal and glial fate, respectively. Transplanted cells were prepared from embryonic day-13.5 fetal spinal cord of transgenic donor rats that express the marker gene human placental alkaline phosphatase to achieve stable and reliable graft tracking. We found that in both developing and adult CNS grafted cells showed long-term survival, morphological maturation, extensive distribution and differentiation into all mature CNS cell types (neurons, astrocytes and oligodendrocytes). Graft-derived neurons also formed synapses, as identified by electron microscopy, suggesting that transplanted neural precursor cells integrated with adult CNS. Furthermore, grafts did not result in any apparent deleterious outcomes. We did not detect tumor formation, cells did not localize to unwanted locations and no pronounced immune response was present at the graft sites. The long-term stability of neuronal-restricted precursors and glial-restricted precursors and the lack of adverse effects suggest that transplantation of lineage-restricted neural precursor cells can

  6. Sirolimus and metformin synergistically inhibit hepatocellular carcinoma cell proliferation and improve long-term survival in patients with HCC related to hepatitis B virus induced cirrhosis after liver transplantation

    PubMed Central

    Shen, Chuan; Peng, Chenghong; Shen, Baiyong; Zhu, Zhecheng; Xu, Ning; Li, Tao; Xie, Junjie

    2016-01-01

    Immunosuppressive agents used postoperatively after liver transplantation (LT) for hepatocellular carcinoma (HCC) favor recurrence and metastasis. Therefore, new effective immunosuppressants are needed. This retrospective study assessed combined sirolimus and metformin on survival of HCC patients after LT. In 2001-2013, 133 HCC patients with LT were divided into four groups: sirolimus and metformin combination (Sir+Met), sirolimus monotherapy (Sir), other immunosuppressants in diabetes mellitus (DM) patients without metformin (No Sir with DM), and other immunosuppressants in patients without DM (No Sir without DM). Kaplan-Meier and Log-rank tests were used to assess survival. Cell proliferation and tumor xenograft assays were performed to disclose the mechanisms underlying the sirolimus and metformin effects. The Sir+Met group showed significantly prolonged survival compared to the other groups. The most significant cytotoxicity was seen in the Sir+Met group, with significantly decreased levels of phosphorylated PI3K, AKT, AMPK, mTOR, 4EBP1 and S6K, compared with the other groups. In agreement, Sir+Met had the highest suppressive effect on tumor growth among all groups (P<0.01). In summary, Sir+Met treatment significantly prolonged survival, likely by suppressing cell proliferation. Therefore, this combination could represent a potential routine-regimen for patients post LT. PMID:27577068

  7. Long-term management of patients with multiple sclerosis.

    PubMed

    Weightman, Cherie

    2006-07-01

    This article explores the challenges of long-term case management for patients who have multiple sclerosis (MS). Currently there is scant research into district nursing input into long-term management of patients who have MS. Until now the role of the community nurses has been confined to palliation or terminal care, focusing on the more physical manifestations of MS. The contemporary role of district nurse is going to evolve to include proactive approaches. Governmental initiatives demand proactive services, and place emphasis on self-care for patients with MS. Themes that emerge from this article relate to the pre-existing skills--such as managing patients with complex needs and the advanced assessment skills--that will be required to achieve this. What is clear is that community nurses already possess many of the prerequisite skills needed for long-term management, and they should not be daunted by this prospect.

  8. Assessing the market for long-term care services.

    PubMed

    Rice, J A; Taylor, S

    1984-02-01

    Traditionally, long-term care services have been used by a diverse marketplace. The chronically ill, developmentally disabled, mentally ill and aging population has looked to long-term care support services as a means of physical and emotional support. Much of the time these services were housed together for the sake of efficiency. The enormous burden these services are creating on the economy, and the growing aging population, have forced the recognition that long-term care service delivery systems must change. Alternate programming for long-term care services that reach out into the community and into individual homes is becoming an attractive approach to meeting the growing demands of the marketplace. Home health, specialized housing and creative funding mechanisms such as HMOs, are examples of initiatives undertaken by healthcare organizations that view diversification as a vehicle for survival. Market research techniques that have been used in other industries are being adapted to the healthcare industry to ensure the proper mix of services that are demanded by older, more knowledgeable consumers. The programs of the future will be market driven, with the ability of the individual to pay for such services playing a significant role. The healthcare provider of today is in a position to serve the community in new ways. By becoming an integral link in the long-term care system and by developing new programs, the organization can serve as a catalyst for change. It is up to the governing bodies and managers of these facilities to become visionaries and to accept responsibility for assessing the market for long-term care services and to guide their organization into the future.

  9. Roadmap to Long-Term Monitoring Optimization

    EPA Pesticide Factsheets

    This roadmap focuses on optimization of established long-term monitoring programs for groundwater. Tools and techniques discussed concentrate on methods for optimizing the monitoring frequency and spatial (three-dimensional) distribution of wells ...

  10. Mental Health in Long Term Care Settings.

    ERIC Educational Resources Information Center

    Shore, Herbert

    1978-01-01

    There are many ways in which long-term care facilities attempt to cope with the mental health problems of the elderly. The author reviews five factors crucial to effective care for the aged in these facilities. (Author/RK)

  11. Long-term-care legal update.

    PubMed

    Fiesta, J

    1998-04-01

    As more nurses move from the acute care setting to long-term-care and home health care, different practice issues arise. To maximize liability protection, nurses must understand the legal issues unique to each delivery system.

  12. Long-Term Care Ombudsman Program

    MedlinePlus

    ... Provided to Persons Living in Long-Term Care Facilities Program data for FY 2013 indicate that long- ... least quarterly Conducted 5,417 training sessions in facilities on such topics as residents’ rights Provided 129, ...

  13. The 2014 Long-Term Budget Outlook

    DTIC Science & Technology

    2014-07-16

    Treasury from the Federal Reserve System, customs duties, estate and gift taxes, and miscellaneous fees and fines. Actual Extended Baseline...Office’s (CBO’s) most recent analysis of the outlook for the federal budget over the long term. My statement today summarizes The 2014 Long-Term Budget...Outlook, which was released yesterday.1 Between 2009 and 2012, the federal government recorded the largest budget deficits relative to the size of

  14. Evidence-based long term care design.

    PubMed

    Calkins, Margaret P

    2009-01-01

    Research on the impact of the built environment in long-term care settings continues to grow. This article focuses on work conducted and published since 2000, when an earlier review on research on dementia and design was published. The vast majority of research that addressed neurological conditions in residents in long-term care settings (assisted living and nursing homes) relates to Alzheimer's disease and related dementias.

  15. Interleukin-12- and Gamma Interferon-Dependent Innate Immunity Are Essential and Sufficient for Long-Term Survival of Passively Immunized Mice Infected with Herpes Simplex Virus Type 1

    PubMed Central

    Vollstedt, Sabine; Franchini, Marco; Alber, Gottfried; Ackermann, Mathias; Suter, Mark

    2001-01-01

    Interferon (IFN) type I (alpha/beta IFN [IFN-α/β]) is very important in directly controlling herpes simplex virus type I (HSV-1) replication as well as in guiding and upregulating specific immunity against this virus. By contrast, the roles of IFN type II (IFN-γ) and antibodies in the defense against HSV-1 are not clear. Mice without a functional IFN system and no mature B and T cells (AGR mice) did not survive HSV-1 infection in the presence or absence of neutralizing antibodies to the virus. Mice without a functional IFN type I system and with no mature B and T cells (AR129 mice) were unable to control infection with as little as 10 PFU of HSV-1 strain F. By contrast, in the presence of passively administered neutralizing murine antibodies to HSV-1, some AR129 mice survived infection with up to104 PFU of HSV-1. This acute immune response was dependent on the presence of interleukin-12 (IL-12) p75. Interestingly, some virus-infected mice stayed healthy for several months, at which time antibody to HSV-1 was no longer detectable. Treatment of these virus-exposed mice with dexamethasone led to death in approximately 40% of the mice. HSV-1 was found in brains of mice that did not survive dexamethasone treatment, whereas HSV-1 was absent in those that survived the treatment. We conclude that in the presence of passively administered HSV-1-specific antibodies, the IL-12-induced IFN-γ-dependent innate immune response is able to control low doses of virus infection. Surprisingly, in a significant proportion of these mice, HSV-1 appears to persist in the absence of antibodies and specific immunity. PMID:11559791

  16. Natural history of imatinib-naive GISTs: a retrospective analysis of 929 cases with long-term follow-up and development of a survival nomogram based on mitotic index and size as continuous variables.

    PubMed

    Rossi, Sabrina; Miceli, Rosalba; Messerini, Luca; Bearzi, Italo; Mazzoleni, Guido; Capella, Carlo; Arrigoni, Gianluigi; Sonzogni, Aurelio; Sidoni, Angelo; Toffolatti, Luisa; Laurino, Licia; Mariani, Luigi; Vinaccia, Vincenza; Gnocchi, Chiara; Gronchi, Alessandro; Casali, Paolo G; Dei Tos, Angelo P

    2011-11-01

    Gastrointestinal stromal tumor (GIST) natural history per se has not been extensively investigated yet, with most data being drawn from large studies with a relevant referral bias. Hence, the estimation of prognosis still remains a critical issue. We retrospectively evaluated 929 GISTs resected between 1980 and 2000 in 35 Italian institutions. A total of 526 patients were found to be suitable for refining risk assessment through the development of a survival nomogram. Median follow-up was 126 months. On testing for potential prognostic parameters, age, tumor site, size, and mitotic index proved to be predictors of OS on both univariable and multivariable Cox model analyses, whereas necrosis and cytonuclear atypia were significant on univariable analysis only. The discriminative ability of the model, including the parameters selected after a backward procedure (C=0.72), improved compared with the National Institutes of Health 2002 (C=0.64) and the National Comprehensive Cancer Network 2007 (C=0.63). On the basis of these data we developed a prognostic nomogram for survival that considers site, size, and mitotic index as continuous variables, providing estimates stratified for patients aged ≤65 and >65 years. This nomogram is a tool based on survival. It overcomes problems that result from artificial categorization of continuous variables. We believe that in the future this should also be attempted by nomograms based on the risk of relapse.

  17. [Psychosocial issues of long-term cancer survivors].

    PubMed

    Weis, J; Faller, H

    2012-04-01

    Although cancer incidence rates are increasing, recent statistical studies suggest that cancer patients are showing higher cure rates as well as improved overall survival rates for most cancer locations. These advances are explained by improved strategies in early diagnoses as well as improved cancer therapies. Therefore, the number of long-term cancer survivors has also increased, but only few studies, especially within the last years, have focused on psychosocial issues of this subgroup. Some studies show that overall quality of life of long-term cancer survivors is quite high and comparable to that of the normal population. Nevertheless, a substantial percentage of former patients shows reduced quality of life and suffers from various sequelae of cancer and its treatment. This review focuses on the most common psychosocial issue of long-term survivors such as reduced psychological wellbeing, neuropsychological deficits and cancer-related fatigue syndrome. Finally, recommendations for problem-oriented interventions as well as improvement of psychosocial care of long-term survivors are given.

  18. Fetal hippocampal CA3 cell grafts enriched with FGF-2 and BDNF exhibit robust long-term survival and integration and suppress aberrant mossy fiber sprouting in the injured middle-aged hippocampus.

    PubMed

    Rao, Muddanna S; Hattiangady, Bharathi; Shetty, Ashok K

    2006-02-01

    Cell transplants that successfully replace the lost neurons and facilitate the reconstruction of the disrupted circuitry in the injured aging hippocampus are invaluable for treating acute head injury, stroke and status epilepticus in the elderly. This is because apt graft integration has the potential to prevent the progression of the acute injury into chronic epilepsy in the elderly. However, neural transplants into the injured middle-aged or aged hippocampus exhibit poor cell survival, suggesting that apt graft augmentation strategies are critical for robust integration of grafted cells into the injured aging hippocampus. We examined the efficacy of pre-treatment and grafting of donor fetal CA3 cells with a blend of fibroblast growth factor-2 (FGF-2) and brain-derived neurotrophic factor (BDNF) for lasting survival and integration of grafted cells in the injured middle-aged (12 months old) hippocampus of F344 rats. Grafts were placed at 4 days after the kainic-acid-induced hippocampal injury and were analyzed at 6 months post-grafting. We demonstrate that 80% of grafted cells exhibit prolonged survival and 71% of grafted cells differentiate into CA3 pyramidal neurons. Grafts also receive a robust afferent input from the host mossy fibers and project efferent axons into the denervated zones of the dentate gyrus and the CA1 subfield. Consequently, the aberrant sprouting of the dentate mossy fibers, an epileptogenic change that typically ensues after the hippocampal injury, was suppressed. Thus, grafts of fetal CA3 cells enriched with FGF-2 and BDNF exhibit robust integration and dampen the abnormal mossy fiber sprouting in the injured middle-aged hippocampus. Because the aberrantly sprouted mossy fibers contribute to the generation of seizures, the results suggest that the grafting intervention using FGF-2 and BDNF is efficacious for suppressing epileptogenesis in the injured middle-aged hippocampus.

  19. Impact of Screening and Risk Factors for Local Recurrence and Survival After Conservative Surgery and Radiotherapy for Early Breast Cancer: Results From a Large Series With Long-Term Follow-Up

    SciTech Connect

    Kunkler, Ian H.; Kerr, Gillian R.; Thomas, Jeremy S.; Jack, Wilma J.L.; Bartlett, John M.S.; Pedersen, Hans C.; Cameron, David A.; Dixon, J. Michael; Chetty, Udi

    2012-07-01

    Purpose: To investigate conventional prognostic factors for ipsilateral breast tumor recurrence (IBTR), distant metastasis (DM), and survival after breast-conserving therapy (BCT) in screen-detected and symptomatic cases on surveillance up to 25 years. Patients and Methods: A total of 1812 consecutive patients in three cohorts (1981-1989, 1990-1992, and 1993-1998) with T12N01M0 invasive breast cancer were treated with BCT (median follow-up, 14 years). Tumor type and grade were reviewed by a single pathologist. Hormone receptor status was measured by immunohistochemistry on tissue microarrays. A Cox proportional hazards model was used to assess independent prognostic variables for relapse and survival. Results: A total of 205 IBTR occurred, with 5-, 10-, 15-, and 20-year actuarial relapse rates of 4.5% (95% confidence interval [CI] 3.35-5.5%), 8.4% (95% CI 7.1-9.8%), 14.1% (95% CI 12.0-16%), and 17.4% (95% CI 14.5-20.2%). Number of nodes, young age, pathologic tumor size, and multifocality were significant factors for IBTR. Three hundred seventy-eight patients developed DM. The actuarial metastatic rate was 12% at 5 years and 17.9% at 10 years. Young age, number of positive nodes, pathologic tumor size, and tumor grade were significant factors for DM relapse. When conventional prognostic indices were taken into account screen-detected cancers showed no improvement in overall relapse or survival rate compared with symptomatic cases but did show a reduced risk of DM after IBTR. After 10 years IBTR relapse continued at a constant rate of 0.87% per annum. Conclusions: The Edinburgh BCT series has shown that screen-detected invasive breast cancers do not have significantly different clinical outcomes compared with symptomatic cases when pathologic risk factors are taken into account. This suggests that these patients be managed in a similar way.

  20. Long-term symptom relief after septoplasty.

    PubMed

    Sundh, Carolina; Sunnergren, Ola

    2015-10-01

    The results for long-term symptom relief after septoplasty are contradictory in reviewed publications but the findings suggest that results are unsatisfactory. In this study, we analyzed and compared short- and long-term symptom relief after septoplasty and factors possibly associated with symptom relief. 111 patients that underwent septoplasty between 2008 and 2010 were included in the study. Medical charts were reviewed for preoperative characteristics and assessments. Data on short-term symptom relief (6 months) were retrieved from the Swedish National Quality Registry for Septoplasty; data on long-term symptom relief (34-70 months) were collected through a questionnaire. Upon the 34-70 month follow-up, 53% of the patients reported that symptoms either remained or had worsened and 83% reported nasal obstruction. Degree of symptom relief was significantly higher among patients not reporting nasal obstruction than among patients reporting nasal obstruction at long-term follow-up. The proportion of patients that reported "my symptoms are gone" declined from 53% after 6 months to 18% after 34-70 months. None of the factors taken into consideration, age at surgery, gender, follow-up time, primary operation/reoperation, history of nasal trauma, self-reported allergy, rhinometric obstruction, or same sided rhinometric, clinical and subjective nasal obstruction were associated with symptom relief. The long-term results after septoplasty are unsatisfactory. A majority of patients report that their symptoms remain after septoplasty.

  1. Long-term outcomes of autoimmune pancreatitis

    PubMed Central

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-01-01

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed. PMID:27678359

  2. Long term complications following 54 consecutive lung transplants

    PubMed Central

    Tabarelli, Walther; Bonatti, Hugo; Tabarelli, Dominique; Eller, Miriam; Müller, Ludwig; Ruttmann, Elfriede; Lass-Flörl, Cornelia; Larcher, Clara

    2016-01-01

    Background Due to the complex therapy and the required high level of immunosuppression, lung recipients are at high risk to develop many different long term complications. Methods From 1993–2000, a total of 54 lung transplantation (LuTx) were performed at our center. Complications, graft and patient survival of this cohort was retrospectively analyzed. Results One/five and ten-year patient survival was 71.4%, 41.2% and 25.4%; at last follow up (4/2010), twelve patients were alive. Of the 39 deceased patients, 26 died from infectious complications. Other causes of death were myocardial infarction (n=1), progressive graft failure (n=1), intracerebral bleeding (n=2), basilary vein thrombosis (n=1), pulmonary emboli (n=1), others (n=7). Surgical complication rate was 27.7% during the first year and 25% for the 12 long term survivors. Perioperative rejection rate was 35%, and 91.6% for the 12 patients currently alive. Infection incidence during first hospitalization was 79.6% (1.3 episodes per transplant) and 100% for long term survivors. Commonly isolated pathogens were cytomegalovirus (56.8%), Aspergillus (29.4%), RSV (13.7%). Other common complications were renal failure (56.8%), osteoporosis (54.9%), hypertension (45%), diabetes mellitus (19.6%). Conclusions Infection and rejection remain the most common complications following LuTx with many other events to be considered. PMID:27293842

  3. Valuing a long-term care facility.

    PubMed

    Mellen, C M

    1992-10-01

    The business valuation industry generally uses at least one of three basic approaches to value a long-term care facility: the cost approach, sales comparison approach, or income approach. The approach that is chosen and the resulting weight that is applied to it depend largely on the circumstances involved. Because a long-term care facility is a business enterprise, more weight usually is given to the income approach which factors into the estimate of value both the tangible and intangible assets of the facility.

  4. Keratoprosthesis: a long-term review.

    PubMed Central

    Barnham, J. J.; Roper-Hall, M. J.

    1983-01-01

    A keratoprosthesis (KP), is an artificial cornea which is inserted into an opacified cornea in an attempt to restore useful vision or, less commonly, to make the eye comfortable in painful keratopathy. Results o a retrospective study of 35 patients, with 55 KP insertions, are reviewed with regard to visual acuity, length of time vision is maintained, retention time, and complication. Overall there were a number of long-term real successes, eith retention of the KP and maintenance of improved vision in eyes not amenable to conventional treatment. Careful long-term follow-up was needed, with further surgical procedures often being necessary. Images PMID:6860613

  5. [Fetal pain: immediate and long term consequences].

    PubMed

    Houfflin Debarge, Véronique; Dutriez, Isabelle; Pusniak, Benoit; Delarue, Eléonore; Storme, Laurent

    2010-06-01

    Several situations are potentially painful for fetuses, such as malformations and invasive procedures. Nociceptive pathways are known to be functional at 26 weeks. Even if it is not possible to evaluate the fetal experience of pain, it is essential to examine its immediate and long-term consequences. As early as the beginning of the second trimester, hemodynamic and hormonal responses are observed following fetal nociceptive stimulation, In experimental studies, long-term changes have been noted in the corticotrop axis, subsequent responses to pain, and behavior after perinatal nociceptive stimulation.

  6. A Long-Term Experimental Case Study of the Ecological Effectiveness and Cost Effectiveness of Invasive Plant Management in Achieving Conservation Goals: Bitou Bush Control in Booderee National Park in Eastern Australia

    PubMed Central

    Lindenmayer, David B.; Wood, Jeff; MacGregor, Christopher; Buckley, Yvonne M.; Dexter, Nicholas; Fortescue, Martin; Hobbs, Richard J.; Catford, Jane A.

    2015-01-01

    Invasive plant management is often justified in terms of conservation goals, yet progress is rarely assessed against these broader goals, instead focussing on short-term reductions of the invader as a measure of success. Key questions commonly remain unanswered including whether invader removal reverses invader impacts and whether management itself has negative ecosystem impacts. We addressed these knowledge gaps using a seven year experimental investigation of Bitou Bush, Chrysanthemoides monilifera subsp. rotundata. Our case study took advantage of the realities of applied management interventions for Bitou Bush to assess whether it is a driver or passenger of environmental change, and quantified conservation benefits relative to management costs of different treatment regimes. Among treatments examined, spraying with herbicide followed by burning and subsequent re-spraying (spray-fire-spray) proved the most effective for reducing the number of individuals and cover of Bitou Bush. Other treatment regimes (e.g. fire followed by spraying, or two fires in succession) were less effective or even exacerbated Bitou Bush invasion. The spray-fire-spray regime did not increase susceptibility of treated areas to re-invasion by Bitou Bush or other exotic species. This regime significantly reduced plant species richness and cover, but these effects were short-lived. The spray-fire-spray regime was the most cost-effective approach to controlling a highly invasive species and facilitating restoration of native plant species richness to levels characteristic of uninvaded sites. We provide a decision tree to guide management, where recommended actions depend on the outcome of post-treatment monitoring and performance against objectives. Critical to success is avoiding partial treatments and treatment sequences that may exacerbate invasive species impacts. We also show the value of taking advantage of unplanned events, such as wildfires, to achieve management objectives at

  7. A long-term experimental case study of the ecological effectiveness and cost effectiveness of invasive plant management in achieving conservation goals: bitou bush control in booderee national park in eastern australia.

    PubMed

    Lindenmayer, David B; Wood, Jeff; MacGregor, Christopher; Buckley, Yvonne M; Dexter, Nicholas; Fortescue, Martin; Hobbs, Richard J; Catford, Jane A

    2015-01-01

    Invasive plant management is often justified in terms of conservation goals, yet progress is rarely assessed against these broader goals, instead focussing on short-term reductions of the invader as a measure of success. Key questions commonly remain unanswered including whether invader removal reverses invader impacts and whether management itself has negative ecosystem impacts. We addressed these knowledge gaps using a seven year experimental investigation of Bitou Bush, Chrysanthemoides monilifera subsp. rotundata. Our case study took advantage of the realities of applied management interventions for Bitou Bush to assess whether it is a driver or passenger of environmental change, and quantified conservation benefits relative to management costs of different treatment regimes. Among treatments examined, spraying with herbicide followed by burning and subsequent re-spraying (spray-fire-spray) proved the most effective for reducing the number of individuals and cover of Bitou Bush. Other treatment regimes (e.g. fire followed by spraying, or two fires in succession) were less effective or even exacerbated Bitou Bush invasion. The spray-fire-spray regime did not increase susceptibility of treated areas to re-invasion by Bitou Bush or other exotic species. This regime significantly reduced plant species richness and cover, but these effects were short-lived. The spray-fire-spray regime was the most cost-effective approach to controlling a highly invasive species and facilitating restoration of native plant species richness to levels characteristic of uninvaded sites. We provide a decision tree to guide management, where recommended actions depend on the outcome of post-treatment monitoring and performance against objectives. Critical to success is avoiding partial treatments and treatment sequences that may exacerbate invasive species impacts. We also show the value of taking advantage of unplanned events, such as wildfires, to achieve management objectives at

  8. Long-term Effectiveness of Online Anaphylaxis Education for Pharmacists

    PubMed Central

    Vale, Sandra; Sanfilippo, Frank M; Loh, Richard; Clifford, Rhonda M

    2014-01-01

    Objective. To evaluate the long-term effectiveness of an Australasian Society of Clinical Immunology and Allergy (ASCIA) anaphylaxis e-learning program compared to lectures or no training. Design. A controlled interrupted-time-series study of Australian pharmacists and pharmacy students who completed ASCIA anaphylaxis e-learning or lecture programs was conducted during 2011-2013. Effectiveness was measured using a validated test administered pretraining, posttraining, and 3 and 7 months after training. Assessment. All learning groups performed significantly better on all posttests compared to the pretest, and compared to a control group (p<0.001). The proportion of e-learners achieving the minimum standard for anaphylaxis knowledge improved from 45% at pretest to 87% at 7 months. Conclusion. The ASCIA e-learning program significantly increased anaphylaxis knowledge. The high proportion of participants achieving the minimum standard at 7 months indicates long-term knowledge change. PMID:25258441

  9. Long-term studies of dopamine agonists.

    PubMed

    Hubble, Jean P

    2002-02-26

    Dopamine agonists have long been used as adjunctive therapy for the treatment of Parkinson's disease (PD). In more recent years these drugs have also been proved safe and effective as initial therapy in lieu of levodopa in the treatment of PD. Long-term levodopa therapy is associated with motor complications, including fluctuating response patterns and dyskinesia. By initially introducing a dopamine agonist as symptomatic drug therapy, it may be possible to postpone the use of levodopa and delay or prevent the development of motor complications. Recently, four clinical trials have explored this hypothesis by comparing the long-term response and side effects of levodopa with dopamine agonist therapy. The drugs studied