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Background The development of cytomegalovirus (CMV) infection after kidney transplant remains a significant cause of posttransplant morbidity, graft loss, and mortality. Despite appropriate antiviral therapy, recipients without previous CMV exposure can currently be allocated a kidney from a donor with previous CMV infection (D+R-) which carries the greatest risk of posttransplant CMV infection and associated complications. Preferential placement of CMV D- organs in negative recipients (R-) has been shown to reduce the risk of viral infection and associated complications. Methods To assess the long-term survival and economic benefits of allocation policy reforms, a decision analytic model was constructed to compare receipt of CMV D- with CMV D+ organ in CMV R- recipients using data from transplant registry, Medicare claims, and pharmaceutical costs. Results For CMV R- patients, receipt of a CMV D- organ was associated with greater average survival (14.3 vs 12.6 years), superior quality-adjusted life years (12.6 vs 9.8), and lower costs ($529 512 vs $542 963). One-way sensitivity analysis demonstrated a survival advantage for patients waiting as long as 30 months for a CMV D- kidney. Conclusions Altering national allocation policy to preferentially offer CMV D- organs to CMV R- recipients could improve survival and lower costs after transplant if appropriately implemented.

The electrophysiological properties of undifferentiated SH-SY5Y cells were examined during cultures prolonged even to 20 days by measuring the passive and active membrane properties at 5 days interval, as well as the spontaneous spiking activity. The results showed that culturing this cell for long time affected not only membrane shape but also their electrophysiological properties. In particular, these cells considerably varied their sodium and potassium voltage-dependent currents, various channels kinetic features and their excitable properties. These modifications would synergically contribute to the bioelectrical conversion of these cells and could be part of a more complex machinery with which the tumoral cell would regulate its survival advantage and resilience. Understanding these processes could add a new clue to the exploitation of this preclinical human neuronal model.

Background: A relationship between body size and longevity has long been appreciated within eukaryotes, especially vertebrates. Introduction: In general, the large size is associated with increased longevity among species of mammals and birds but is associated with decreased longevity within individual species such as dogs and mice. In this study, we examined the relationship between measures of individual body size and longevity in a captive population of speckled cockroaches (Nauphoeta cineria). Methods: Newly molted adults of both sexes were removed from a mass colony housed in multiple terraria and housed individually with food and water provided ad libitum for the duration of their lifespan. Thrice weekly, the status (i.e., live/dead) of individual cockroaches was noted for the duration of the study. Individuals found dead were weighed and measured to obtain body mass and morphometric measures, and the age at the time of death was recorded. The relationship between body size and lifespan was assessed. Result: Contrary to what is commonly seen within vertebrates, large cockroaches were longerlived than their smaller counterparts. Specifically, body mass, body length, and pronotum width were all significantly correlated with the age at death in a mixed population of males and females (n = 94). In addition, we found that the longevity of a historically larger population in terms of both body mass and body length was significantly longer-lived than the population used in this study. Conclusion: These data indicate there is a significant interaction between body size and aging in this species and that increased size results in a survival advantage. There is evidence in the literature indicating that a positive relationship between size and longevity may be common in insects.

PurposeVarious theories predict that firm buyouts survive longer than newly created firms. The study aims to know whether it is the case for worker-owned firms (WOFs), i.e. firms owned and controlled mostly by their workers.Design/methodology/approachThe author conducted a comparative survival analysis of French WOFs distinguished by their entry mode (i.e. newly created, worker buyouts (WBOs) of sound conventional firms, WBOs of conventional firms in difficulty or WBOs of non-profit organizations).FindingsThe hazard of exit is 32% lower for WBOs of sound conventional firms than newly created WOFs, 18% for WBOs of conventional firms in difficulty and 64% for WBOs of non-profit organizations. The current study confirms that WBOs, even of conventional firms in difficulty, have on average a survival advantage over newly created WOFs. Surprisingly, the author also shows that this survival advantage is similar across sectors with different knowledge intensity but is lower in high capital-intensive sectors than in low capital-intensive ones.Research limitations/implicationsEndogeneity issues limit the scope of the results and should be tackled in future research. Overall, these findings show that WOFs are composed of groups with different survival likelihoods that are obscured if one only looks at the aggregate population.Practical implicationsWith caution, support agencies could foster WBOs of firms in difficulty and of non-profit organizations as viable forms of entrepreneurship.Originality/valueThe current study offers the first survival analysis distinguishing four modes of entry among WOFs.

This paper shows that the universal female survival advantage evades all the countries of South Asia, except Sri Lanka. Consequently, contrary to the global trend, these countries have more older men than older women in their populations. In view of this, the paper first develops a theoretical model (using the life-course perspective) to explain the mechanisms behind the possible persistence of this female deficit, i.e. the (older) missing women phenomenon, and highlights why this model may apply to South Asian countries. This discussion addresses the higher mortality of females' compared to males at each stage of the life course that culminate in old age (the life-course effect), the role of conflict and natural disasters that affect female mortality more adversely than male mortality (cohort effects), or a combination of the two. Subsequently, the paper calculates the extent of the female deficit in South Asian countries. The results of the calculation accord with the theoretical discussion by allowing the classification of the older missing women phenomenon as a life-course effect in some countries (e.g. India), a cohort effect in other countries (e.g. Nepal), and a combination of the two in specific countries (e.g. Pakistan).

Human beings are predisposed to identifying false patterns in statistical noise, a likely survival advantage during our evolutionary development. Moreover, humans seem to prefer "positive" results over "negative" ones. These two cognitive features lay a framework for premature adoption of falsely positive studies. Added to this predisposition is the tendency of journals to "overbid" for exciting or newsworthy manuscripts, incentives in both the academic and publishing industries that value change over truth and scientific rigour, and a growing dependence on complex statistical techniques that some reviewers do not understand. The purpose of this article is to describe the underlying causes of premature adoption and provide recommendations that may improve the quality of published science.

To examine the length of a hexanucleotide expansion in C9orf72, which represents the most frequent genetic cause of frontotemporal lobar degeneration and motor neuron disease, we employed a targeted amplification-free long-read sequencing technology: No-Amp sequencing. In our cross-sectional study, we assessed cerebellar tissue from 28 well-characterized C9orf72 expansion carriers. We obtained 3507 on-target circular consensus sequencing reads, of which 814 bridged the C9orf72 repeat expansion (23%). Importantly, we observed a significant correlation between expansion sizes obtained using No-Amp sequencing and Southern blotting (P = 5.0 × 10−4). Interestingly, we also detected a significant survival advantage for individuals with smaller expansions (P = 0.004). Additionally, we uncovered that smaller expansions were significantly associated with higher levels of C9orf72 transcripts containing intron 1b (P = 0.003), poly(GP) proteins (P = 1.3 × 10− 5), and poly(GA) proteins (P = 0.005). Thorough examination of the composition of the expansion revealed that its GC content was extremely high (median: 100%) and that it was mainly composed of GGGGCC repeats (median: 96%), suggesting that expanded C9orf72 repeats are quite pure. Taken together, our findings demonstrate that No-Amp sequencing is a powerful tool that enables the discovery of relevant clinicopathological associations, highlighting the important role played by the cerebellar size of the expanded repeat in C9orf72-linked diseases., DeJesus-Hernandez et al. employ an innovative long-read sequencing method to examine the length of the expanded C9orf72 repeat that represents the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis. Smaller expansion size confers a survival benefit for patients.

Implantable cardioverter-defibrillators (ICDs) have been shown to have survival advantage in advanced heart failure patients. Few studies have evaluated the role of ICDs in patients supported with continuous-flow left ventricular assist devices (CFVADs). We aimed to evaluate the impact of ICD and CFVAD on heart transplant (HTx) waiting list survival. We queried the United Network for Organ Sharing (UNOS) thoracic transplant database between years 2007 and 2016 for patients aged ≥ 18 years listed for HTx. Patients receiving devices other than CFVAD were excluded. Patients were divided into groups-with and without CFVAD and further subdivided into groups-with and without ICD use. Kaplan-Meier curves were used to evaluate the survival outcomes. There were 34 860 patients listed for HTx during study period of which 11 481 (32%) had a CFVAD and 26 139 (75%) had an ICD. Within CFVAD group, patients with ICD were older, more likely male, with higher creatinine and listed as UNOS status 1A. In the No-CFVAD group, 1-year waitlist survival was significantly better with ICD use (81% vs. 73%, P < .0001); however, in CFVAD patients, 1-year survival with ICD use was comparable to No-ICD use (95% vs. 94%, P = .1). Use of ICD is associated with significantly better heart transplant waitlist survival in patients not supported by CFVAD. In patients supported with CFVAD, the ICD does not offer additional survival benefit.

Hepatopancreatoduodenectomy (HPD) can offer a survival advantage in selected patients with locally advanced gall bladder cancer (GBC). While the safety and feasibility of minimally invasive radical cholecystectomy have been recently documented, laparoscopic HPD for GBC has not been previously reported. A 73-year-old male with GBC infiltrating the bile duct underwent laparoscopic HPD to achieve R0 resection. The patient had an uneventful post-operative course except for delayed gastric emptying that improved with conservative management. The feasibility of laparoscopic HPD for locally advanced GBC reported in the present case needs to be documented in a large case series.

ObjectiveTo comprehensively explore contemporary differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with chronic haemodynamically significant aortic regurgitation (AR).MethodsConsecutive patients with chronic ≥moderate-severe AR from a tertiary referral centre (2006–2017) were included. All-cause mortality, surgical indications and aortic valve surgery (AVS) were analysed.ResultsOf 798 patients (296 BAV-AR, age 46±14 years; 502 TAV-AR, age 67±14 years, p20 mm/m2; similar thresholds were observed for BAV-AR patients.ConclusionBAV-AR patients were two decades younger than TAV-AR and underwent AVS more frequently, resulting in a considerable real-life survival advantage for BAV-AR that was determined primarily by age and not valve anatomy. Pragmatically, regardless of valve anatomy, patients with haemodynamically significant AR and age >50–55 years require a low-threshold for surgical referral to prevent symptom development where LVEF 20 mm/m2 seem appropriate referral thresholds.

Summary Background The effects of subinhibitory concentrations (sub-MICs) of antibacterial agents on the biofilm-forming ability of Staphylococcus aureus require further study. Aim To investigate the effects of sub-MICs of chlorhexidine and mupirocin on biofilm formation in clinical meticillin-resistant Staphylococcus aureus (MRSA) isolates. Methods MRSA isolates were collected from patients with bloodstream infections at a tertiary care hospital. The basal level of biofilm formation and biofilm induction by sub-MICs of chlorhexidine and mupirocin were evaluated by measuring biofilm mass stained with Crystal Violet. Findings Of the 112 MRSA isolates tested, 63 (56.3%) and 44 (39.3%) belonged to sequence type (ST)5 and ST72 lineages, respectively, which are the predominant healthcare- and community-associated clones in South Korea. ST5 isolates were more likely to have chlorhexidine MIC ≥4 (73.0% vs 29.5%), resistance to mupirocin (23.8% vs 0%), agr dysfunction (73.0% vs 9.1%), and qacA/B gene (58.7% vs 2.3%) compared to ST72 isolates. The basal level of biofilm formation ability was frequently stronger in ST72 isolates compared to ST5 isolates (77.3% vs 12.7%). Sub-MICs of chlorhexidine and mupirocin promoted biofilm formation in 56.3% and 53.6%, respectively, of all isolates. Biofilm induction was more prevalent in ST5 isolates (85.7% for chlorhexidine, 69.8% for mupirocin) than in ST72 isolates (15.9% for chlorhexidine, 27.3% for mupirocin). Conclusion Sub-MICs of chlorhexidine and mupirocin promoted biofilm formation in half of the clinical MRSA isolates. Our results suggest that ST5 MRSA biofilm can be induced together with some other bacterial virulent factors following exposure to chlorhexidine, which might confer a survival advantage to this clone in the healthcare environment.

Background: A female survival advantage in cutaneous melanoma has been long recognized. However, whether this extends across all age groups, with risk stratification using the latest prognostic staging system or in the current era of efficacious systemic therapies is unknown. Therefore, we evaluated whether sex-based differences in melanoma survival persisted within a recent population-based patient cohort with consideration of these factors. Materials and Methods: We identified stage II−IV cutaneous melanoma patients from 2010 to 2014 Surveillance, Epidemiology, and End Results cancer registries data. We recalculated stage per American Joint Committee on Cancer 8th edition guidelines. Cancer-specific survival (CSS) was estimated by using the Kaplan–Meier method and multivariable Cox proportional hazards regression. Results: Of 16,807 patients (39.8% female), 8,990 were stage II, 4,826 stage III, and 2,991 stage IV at diagnosis. Unadjusted 3-/5-year CSS estimates for females versus males were 64.2% versus 59.7%, and 53.5% versus 49.9%, respectively, p ≤ 0.0001. Five-year CSS varied within each stage and across age strata of

Background The survival advantage of radiotherapy for patients with stage IV classic Hodgkin lymphoma (HL) has not been adequately evaluated. Methods We analyzed patients with stage IV HL enrolled from the Surveillance, Epidemiology, and End Results (SEER) registry from January 2000 to December 2012. Propensity score (PS) analysis with 1:2 matching was performed to ensure well-balanced characteristics of the comparison groups. Kaplan-Meier and Cox proportional hazardous model were used to evaluate the overall survival (OS), cancer-specific survival (CSS), the hazards ratio (HR) and corresponding 95% confidence intervals (95% CI). Results Overall, for all patients with stage IV HL, receiving radiotherapy was associated with both significantly improved OS and CSS. Radiotherapy to any lesions could independently improve the OS and CSS by 30% to 36% in the multivariate analyses before and after PS matching (PSM), with the best improvement of 33% to 40% observed for patients with nodular sclerosis (P < 0.05) among all HL pathological types. In particular, radiotherapy, most likely to the residual site, was more pronouncedly associated with the improvement in survival for patients with stage IV HL who were young (age

The long-term mortality in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) is unexpectedly decreased or at least not increased regardless of several mortality risk factors that these diseases share with other chronic immune-mediated rheumatic diseases. The genetic and immunological profile of PMR/GCA patients is unique, therefore, the hypothesis that this profile provides some survival advantage to PMR/GCA patients should be considered. The longevity is a phenomenon that was demonstrated to be familial. The familial aggregation of longevity can be studied by analysis of life expectancy in family members. Here we test the hypothesis of the aggregation of an increased longevity in the families of PMR/GCA patients. We compared the age of death of 358 parents of 179 PMR and GCA patients with corresponding data retrieved from 506 parents of 253 randomly collected age and sex-matched controls. The number of nonagenarian (≥ 90-year -old) mothers of PMR/GCA patients was significantly higher (OR = 2.34, 95%CI 1.11–11.95, p p = 0.003). Our data suggest the familial aggregation of nonagenarians in PMR/GCA patients.

Historical relationships between socio‐economic status and mortality remain poorly understood. This is particularly the case in England, due to a lack of status indicators in available sources especially before c. 1850. This study uses the paternal occupational descriptors routinely recorded in Anglican baptism registers from 1813–37 to compare infant and early childhood mortality by social status. The sample consists of eight of the Cambridge Group family reconstitution parishes, which make it possible to investigate the contributions of environment as well as household characteristics. The main variable of interest was an individual‐level continuous measure of wealth based on ranking paternal occupations by the propensity for their movable wealth to be inventoried upon death. The findings show that wealth conferred no clear survival advantage in infancy, once differences in average mortality levels between parishes were adjusted for. However, wealth was associated with higher survival rates in early childhood, especially in the second year of life, and this pattern persisted after adjustment for parish‐level effects. The striking exception to this pattern was labourers, who were among the poorest of fathers but whose children enjoyed relatively low mortality. Thus socio‐economic differentials in mortality were present in early nineteenth‐century England; however, they were small, age‐specific, and non‐linear.

The reduction of the dismally high mortality of current end-stage renal disease patients maintained on conventional standard haemodialysis (HD) remains an unmet medical need. Online haemodiafiltration (HDF) modes with various sites of fluid substitution (post-, pre-, mixed- and mid-dilution) are increasingly used worldwide as promising alternatives to conventional HD. Large scale cohort studies, post hoc analyses of randomized trials, and individual participant meta-analyses suggest that post-dilution and pre-dilution, especially with high substitution volumes, improve outcomes compared with conventional standard HD. However, there is no definitive proof of a survival advantage of HDF over standard HD. The different modes of high-volume HDF should be considered a therapeutic platform allowing to personalize and tailor routine HDF treatment. The selection of the HDF mode should be made according to individual patient characteristics. Utilizing high retention onset membranes, expanded haemodialysis (HDx) can achieve the same solute removal performance as HDF. Subgroups of high-volume OL-HDF patients could benefit from HDx. Ongoing and future trials should provide definitive proof for the superiority of high-volume OL-HDF over conventional HD or HDx to give guidance for the most favourable mode of dialytic therapy for clinical use.

Overall survival (OS) in patients with multiple myeloma (MM) varies across racial and ethnic groups [1]. Prior to the early 2000s, black patients were shown to have a survival advantage over white ...

Background: Although the survival advantage of bilateral internal thoracic artery grafting (BITA) is well known in patients undergoing coronary artery bypass grafting (CABG), this technique has not been widely adopted. This is mainly because of the increased risk of deep sternal wound infections (DSWI) associated with its use. However, in recent years the overall risk of DSWI has decreased. This is mainly because of strategies that have been adopted to decrease the risk of these infections in patients undergoing CABG. Conclusion: In this review we identified DSWI preventive strategies and described them in detail so that their use by surgeons can be increased. This would minimize the risk of DSWI after BITA grafting and maximize the use of this highly effective surgical technique.

The National Cancer Survivorship Initiative through the National Health Service (NHS) improvement in the UK started the implementation of stratified pathways of patient-initiated follow-up (PIFU) across various tumor types. Now the initiative is continued through the Living With and Beyond Cancer program by NHS England. Evidence from non-randomized studies and systematic reviews does not demonstrate a survival advantage to the long-established practice of hospital-based follow-up regimens, traditionally over 5 years. Evidence shows that patient needs are inadequately met under the traditional follow-up programs and there is therefore an urgent need to adapt pathways to the needs of patients. The assumption that hospital-based follow-up is able to detect cancer recurrences early and hence improve patient prognosis has not been validated. A recent survey demonstrates that follow-up practice across the UK varies widely, with telephone follow-up clinics, nurse-led clinics and PIFU becoming increasingly common. There are currently no completed randomized controlled trials in PIFU in gynecological malignancies, although there is a drive towards implementing PIFU. PIFU aims to individualize patient care, based on risk of recurrence and holistic needs, and optimizing resources. The British Gynaecological Cancer Society wishes to provide the gynecological oncology community with guidance and a recommendations statement regarding the value, indications, and limitations of PIFU in endometrial, cervical, ovarian, and vulvar cancers in an effort to standardize practice and improve patient care. [Abstract copyright: © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.]

Patients with high-risk localized prostate cancer benefit from multimodality therapy of curative intent. Androgen-deprivation therapy (ADT) combined with radiation improves survival in this population. However, prior clinical trials of neoadjuvant ADT and surgery failed to consistently demonstrate a survival advantage. The development of novel, more potent hormonal agents presents an opportunity to revisit the potential for neoadjuvant therapy to improve long-term outcomes for patients with localized prostate cancer. We review recent advances in neoadjuvant approaches for prostate cancer and emerging clinical trials data supporting the use of neoadjuvant therapy prior to radical prostatectomy.

Since the initial report of long-term survival after lung transplantation (LT) in 1983, there has been remarkable progress in the field and LT is now the gold-standard therapy for patients with end-stage lung disease. It confers a significant survival advantage and improves the quality of life in patients who often have few other treatment options. However, LT remains a complex undertaking and establishing and maintaining an LT program is resource intensive with multiple potential barriers. In this article, we focus on disparities in LT and the potential solutions to improving access to LT.

BackgroundThe current WHO classification integrates histological and molecular features of brain tumors. The aim of this study was to identify generalizable topological patterns with the potential to add an anatomical dimension to the classification of brain tumors.MethodsWe applied non-negative matrix factorization as an unsupervised pattern discovery strategy to the fine-grained topographic tumor profiles of 936 patients with primary and secondary brain tumors. From the anatomical features alone, this machine learning algorithm enabled the extraction of latent topological tumor patterns, termed meta-topologies. The optimal parts-based representation was automatically determined in 10,000 split-half iterations. We further characterized each meta-topology’s unique histopathologic profile and survival probability, thus linking important biological and clinical information to the underlying anatomical patternsResultsIn primary brain tumors, six meta-topologies were extracted, each detailing a transpallial pattern with distinct parenchymal and ventricular compositions. We identified one infratentorial, one allopallial, three neopallial (parieto-occipital, frontal, temporal) and one unisegmental meta-topology. Each meta-topology mapped to distinct histopathologic and molecular profiles. The unisegmental meta-topology showed the strongest anatomical-clinical link demonstrating a survival advantage in histologically identical tumors. Brain metastases separated to an infra- and supratentorial meta-topology with anatomical patterns highlighting their affinity to the cortico-subcortical boundary of arterial watershed areas.ConclusionsUsing a novel data-driven approach, we identified generalizable topological patterns in both primary and secondary brain tumors Differences in the histopathologic profiles and prognosis of these anatomical tumor classes provide insights into the heterogeneity of tumor biology and might add to personalized clinical decision making.

Background Current guidelines consider all cases of papillary thyroid carcinoma (PTC) smaller than 4 cm and without extrathyroidal extension (ETE) and/or lymph node metastases as belonging to the same prognostic group, and therefore the recommendation is for uniform treatment. Xing draws our attention to a small subgroup with Duet Mutations (BRAF E600 and TERT 3636 genes) that are aggressive biologically and should be treated differently. Thus the aim of the present study is to test the validity of this recommendation. Methods A Markovian Model is used to evaluate the above hypothesis. Results A Monte Carlo sensitivity test shows a 5.6 year survival advantage for patients with low-grade PTC, who have the Duet Mutations, and were treated by total thyroidectomy rather than hemithyroidectomy. Conclusions We conclude that there is a place for routine molecular tests in low-risk patients with PTC.

Background Despite the demonstrated survival advantage in end-stage kidney disease (ESKD) patients of a preemptive living donor kidney transplantation (LDKT), there has been a decline in LDKT among African-American and Hispanic populations. Methods We performed a scoping review and summarized the evidence about the use of technology-based interventions (TBI) to not only increase knowledge and awareness of LDKT but to also link living donors with transplant candidates. Results We evaluated 31 studies and characterized them into "transplant-candidate facing" TBI, "transplant donor facing" TBI and "interactive websites" targeting both donors and candidates. For the patient-facing interventions, 60% of studies suggested an increased likelihood of linking possible donors and candidates. The donor-facing interventions showed an increase in donor awareness and 75% of these interventions suggested increasing donor- candidate linkage. Conclusions This study also demonstrates that TBI (regardless of medium) that are accessible and customized to the specific target population can potentially increase linkage of donors to recipients and serve as effective guides to connect potential donors to transplant candidates.

INTRODUCTION AND OBJECTIVE:Previous studies on genitourinary malignancies have demonstrated a survival advantage for patients affected by high BMI, attributed to an inverse correlation between onco...

Introduction: Ado-trastuzumab emtansine (T-DM1) is an antibody–drug conjugate and its survival advantage has been shown in advanced human epidermal growth factor receptor 2 (HER2)–positive breast cancer. However, clinical trials underrepresent patients ⩾65 years of age, leading to a lack of information in this population. We analyzed the real-world outcomes of older women who were treated with T-DM1 therapy. Methods: We performed a multicenter, observational, retrospective analysis of patients aged ⩾65 years treated with T-DM1. A total of 93 patients from 10 cancer centers were involved in the study. Our goal was to determine the survival, response rates, and toxicity profile in T-DM1–treated patients, as well as the factors that influence survival. Results: Median follow-up was 12.2 months. Objective response rate was 29%. Median progression-free survival (PFS) and overall survival (OS) were 8.47 and 15.0 months, respectively. In multivariate analysis, Eastern Cooperative Oncology Group Performance Score 2 was found to be an independent prognostic factor for worse PFS (hazard ratio [HR] 1.81, p = 0.032) and OS (HR 2.33, p = 0.006). Any adverse event (AE) was seen in 92.5% of patients; grade 3 or 4 AEs were seen in 30.1%. Dose reduction or treatment discontinuation rates were 11.8% and 6.5%, respectively. Conclusion: The efficacy of T-DM1 was acceptable and it was generally well-tolerated among older patients with advanced HER2-positive breast cancer.

Leukemia-transformed multipotential hematopoietic cells have acquired the increased self-renewal capacity and impaired myeloid differentiation to mature blood cells. The emergence of symptomatic leukemia also critically requires the acquisition of growth and survival advantage in leukemic cells. Untreated leukemia patients usually demonstrated a progressive process. However, spontaneous remission occasionally occurred in a very small number of leukemia patients, which frequently followed a febrile episode and antibiotic treatment and was generally attributed to the activation of anti-neoplastic activities. Here we report a 63-year-old Chinese man who presented with the main complaints of abdominal pain, febrile episode and urticaria-like skin lesions. He was diagnosed with acute myeloid leukemia (AML-M4) with t(8;21)(q22;q22)/RUNX1-RUNX1T1 on the basis of morphological, immunological, cytogenetic and molecular analysis. He also had a mutated FLT3-TKD gene. He was treated with antibiotics and glucocorticoid for the gastrointestinal infection and the urticaria-like skin lesions. The infection and skin lesions were quickly resolved. Unexpectedly, along with the relief of the febrile episode, abdominal symptoms and skin lesions, he achieved a hematological remission. After relapse, repeating this treatment resulted in the second hematological remission. These recapitulated treatment responses strongly suggested that inflammatory stresses arising from the gut inflammatory lesions, which could be largely mitigated by antibiotic and glucocorticoid treatment, sustained the growth and survival advantage of the leukemic cells.

Xin-Yue Liang,1,2 Wen Li,1,2 Fang Liu,1,2 Xin-Dan Kang1,2 1Medical School of Chinese People’s Liberation Army (PLA), Beijing, People’s Republic of China; 2Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Wen LiMedical School of Chinese People’s Liberation Army (PLA), Yard 28, Fuxing Street, Haidian District, Beijing, People’s Republic of ChinaTel +86 13911589119Fax +86 10 55499307Email liwen2000@yahoo.comPurpose: The main aim of this study was to compare the efficacy and safety of different biliary drainage strategies, including percutaneous transhepatic biliary drainage (PTBD) versus endoscopic biliary stenting (EBS) and unilateral versus bilateral stenting, in patients with unresectable malignant hilar biliary strictures (MHBSs).Patients and Methods: This was a retrospective review of patients with inoperable MHBSs who underwent biliary drainage by either EBS or PTBD. Efficacy and safety were compared between the two pathways and between unilateral and bilateral stenting in the EBS group. The survival duration was analyzed with K-M curves and Log rank tests.Results: From January 2015 to December 2019, a total of 206 (126: EBS and 80: PTBD) patients with MHBSs were enrolled in our study and underwent 270 procedures (173: EBS and 97: PTBD). Bilateral stenting was superior to unilateral stenting in terms of clinical success (69.6% vs 50.6%, p=0.039), especially for patients with Bismuth type IV (70.0% vs 30.3%, p=0.002). A higher decrease in bilirubin was seen with PTBD in patients with Bismuth types III–IV (66.9 vs 36.7, p=0.006). A survival advantage was seen in successful drainage (227 days vs 82 days, p< 0.001), lower tumor-node-metastasis (TNM) scores (I–II) (195 days vs 139 days, p=0.012), and cholangiocarcinoma (184 days vs 84 days, p=0.001).Conclusion: For patients with advanced MHBSs, bilateral stenting may achieve a better drainage effect than unilateral stenting, and PTBD may have a better performance in relieving cholestasis than EBS. Successful drainage and cholangiocarcinoma may provide greater long-term survival benefits.Keywords: inoperable hilar malignancy, endoscopic biliary stenting, percutaneous transhepatic biliary drainage, survival

Males exhibit higher incidence and worse prognosis for the majority of cancers, including glioblastoma (GBM). Disparate survival may be related to sex-biased responses to treatment, including radiation. Using a mouse model of GBM, we show that female cells are more sensitive to radiation, and that senescence represents a major component of the radiation therapeutic response in both sexes. Correlation analyses revealed that the CDK inhibitor p21 and irradiation induced senescence were differentially regulated between male and female cells. Indeed, female cellular senescence was more sensitive to changes in p21 levels, a finding that was observed in both wildtype and transformed murine astrocytes and patient-derived GBM cell lines. Using a novel Four Core Genotypes model of GBM, we further show that sex differences in p21-induced senescence are patterned by gonadal sex. These data suggest that sex differences in p21 induced senescence contribute to the female survival advantage in GBM.

Purpose: This study aimed to identify the risk of neurodegenerative death (ND) that former Olympians endure due to their participation in sports grouped based on presumed repeated shocks to the head, and to understand the impact of their participation in such elite sports on their total longevity.Materials and Methods: The cohort included all former US Olympians, who participated in the Olympic Games (OG) between 1948 and 1972, and whose vital status and causes of death were verified (n = 2,193). Olympic sports were classified into three categories of exposure: Collision (the highest presumed risk of repeated shocks to the head), Contact, and No-Contact. The Fine-Gray competing risk regression model was used to compare the risk of ND where the No-Contact category was a reference group. The years-saved analysis was performed to quantify the number of years saved or lost to ND and total longevity compared with the US general population.Results: A total of 65 NDs were identified. Collision sports Olympians had a 3.11 (95% CI: 1.31–7.40) higher risk of ND while the Contact group showed a risk of 0.56 (95% CI: 0.21–1.48) compared with the No-Contact sports Olympians. Compared with the general population, the Collision group lost 0.61 (95% CI: -1.16—0.06) years of life from ND, while the Contact group saved 0.4 (95% CI: 0.26–0.54) and the No-Contact group saved 0.09 (-0.09–0.28) years of life up to the age of 90. Regarding the total longevity, Collision, Contact, and No-Contact groups saved 4.67 (95% CI: 3.13–6.22), 5.8 (95% CI: 4.93–6.67), and 6.24 (95% CI: 5.57–6.92) years of life, respectively, from all causes of death.Conclusion: There is an elevated risk of ND among US Olympians, who engaged in sports with the highest presumed risk of repeated shocks to the head compared with those exposed to no such hazard. Such risk does not jeopardize the total longevity among Olympians in Collision sports.

Background: Although concurrent radio-chemotherapy and adjuvant temozolomide (TMZ) treatment for six cycles has been established as a standard of care for newly diagnosed glioblastoma multiforme (GBM) patients, the recommended duration of adjuvant TMZ remains a matter of debate. Methods: We conducted this historical cohort study to evaluate the survival benefit and toxicity profile of administration of 12 cycles of adjuvant TMZ in patients with newly diagnosed histologically confirmed GBM and compared this data with that of patients who completed the standard 6 cycles without disease progression. After concurrent radio-chemotherapy, TMZ was administered for 6 cycles (group 1) and for 12 cycles (group 2). Univariate and multivariate analysis (using the Cox proportional hazards model) were performed to identify factors affecting progression free survival (PFS) and overall survival (OS). Results: Between June 2016 and February 2018, 55 patients were eligible. Patients in Group 1 (n=29) had a median PFS of 15 months (95% CI: 10.215-19.785), while those in Group 2 (n=26) had a median PFS of 18 months (95% CI: 16.611-19.389). After a median follow up duration of 20 months (range: 12-41), the median OS was 18 months (95% CI: 13.420-22.580) in Group 1 and 22 months (95% CI: 18.777-25.223) in Group 2. There was no statistically significant correlation between the number of chemotherapy cycles and PFS (P = 0.513) or OS (P = 0.867). The extent of surgical resection was the only independent prognostic factor for both PFS (P = 0.015) and OS (P = 0.028) by multivariate analysis. Three grade ≥3 hematologic toxicity were encountered in three patients. One in the six-cycle group (neutropenia), and two in the 12-cycle group (one had neutropenia and the other one developed thrombocytopenia). No statistically significant difference in the toxicity profile between both groups.Conclusions: Although extending adjuvant TMZ to 12 cycles was not associated with increased toxicities, it did not significantly improve PFS or OS. So we do not recommend any modifications in the six months protocol until further studies are performed. It should be weighed against the compromised quality of life and the cost to the health care system.

We recently demonstrated TCRγδ + T-ALL as a distinct subgroup from TCRαβ + T-ALL at genomic level. TCRγδ + T-ALL subgroup possess significant survival advantage compared to TCRαβ + T-ALL. In the present study, functional level differences in these two subgroups of T-ALL were studied to understand the immune scenario contributing to survival benefit of TCRγδ + T-ALL subgroup. TCRγδ clonal T-ALL patients showed significantly high levels of γδ T cells compared to TCRαβ clonal T-ALL patients. TCRγδ + T-ALL patients expressed significantly high central memory and terminally differentiated (TemRA) Vδ1 and Vδ2 T cells. TCR γδ clonal leukemic blasts stimulated increased number of Vδ2 T cells from healthy lymphocytes. TCR γδ clonal leukemic blasts were able to form efficient immune synapse with effector γδ T cells. The differences in immunophenotype, cytotoxicity and immune synapse formations corroborate TCRγδ + T-ALL as a distinct subgroup from TCRαβ + T-ALL patients and explain the survival benefit of TCRγδ + T-ALL patients.