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Background:It has been proposed that GAS may form biofilms. Biofilms are microbial communities that aggregate on a surface, and exist within a self-produced matrix of extracellular polymeric substances. Biofilms offer bacteria an increased survival advantage, in which bacteria persist, and resist host immunity and antimicrobial treatment. The biofilm phenotype has long been recognized as a virulence mechanism for many Gram-positive and Gram-negative bacteria, however very little is known about the role of biofilms in GAS pathogenesis.Objective:This review provides an overview of the current knowledge of biofilms in GAS pathogenesis. This review assesses the evidence of GAS biofilm formation, the role of GAS virulence factors in GAS biofilm formation, modelling GAS biofilms, and discusses the polymicrobial nature of biofilms in the oropharynx in relation to GAS.Conclusion:Further study is needed to improve the current understanding of GAS as both a monospecies biofilm, and as a member of a polymicrobial biofilm. Improved modelling of GAS biofilm formation in settings closely mimicking in vivo conditions will ensure that biofilms generated in the lab closely reflect those occurring during clinical infection.

Donation after circulatory death (DCD) in the UK has tripled in the last decade. However, outcomes following DCD liver transplantation are worse than for donation after brainstem death (DBD) liver transplants. This study examines whether a recipient should accept a "poorer quality" DCD organ or wait longer for a "better" DBD organ.Data were collected on 5,825 patients who were registered on the elective waiting list for a first adult liver-only transplant and 3,949 patients who received a liver-only transplant in the UK between 1 January 2008 and 31 December 2015. Survival following deceased donor liver transplantation performed between 2008 and 2015 was compared by Cox regression modelling to assess the impact on patient survival of accepting a DCD liver compared to deferring for a potential DBD transplant.A total of 953 (23%) of the 3,949 liver transplantations performed utilised DCD donors. Five-year post-transplant survival was worse following DCD than DBD transplantation (69.1% [DCD] vs. 78.3% [DBD]; p0.0001: adjusted hazard ratio [HR] 1.65; 95% CI 1.40-1.94). Of the 5,798 patients registered on the transplant list, 1,325 (23%) died or were removed from the list without receiving a transplant. Patients who received DCD livers had a lower risk-adjusted hazard of death than those who remained on the waiting list for a potential DBD organ (adjusted HR 0.55; 95% CI 0.47-0.65). The greatest survival benefit was in those with the most advanced liver disease (adjusted HR 0.19; 95% CI 0.07-0.50).Although DCD liver transplantation leads to worse transplant outcomes than DBD transplantation, the individual's survival is enhanced by accepting a DCD offer, particularly for patients with more severe liver disease. DCD liver transplantation improves overall survival for UK listed patients and should be encouraged.This study looks at patients who require a liver transplant to save their lives; this liver can be donated by a person who has died either after their heart has stopped (donation after cardiac death [DCD]) or after the brain has been injured and can no longer support life (donation after brainstem death [DBD]). We know that livers donated after brainstem death function better than those after cardiac death, but there are not enough of these livers for everyone, so we wished to help patients decide whether it was better for them to accept an early offer of a DCD liver than waiting longer to receive a "better" liver from a DBD donor. We found that patients were more likely to survive if they accepted the offer of a liver transplant as soon as possible (DCD or DBD), especially if their liver disease was very severe.

Biofilms represent densely packed aggregates of microorganisms encased in a self-produced matrix of extracellular polymeric substance, helping in their attachment to biotic and abiotic surfaces conferring them survival advantage in unfavorable conditions. The stages in biofilm formation are complex, the knowledge of which is important as their role in a diverse range of dermatological diseases is being constantly unraveled. Due to their chronic persistent nature, inability of routine culture techniques to detect them and their resistance to standard antimicrobial therapy, they pose a unique challenge to the treating clinician. Although various novel treatment options are available, they show varying degrees of efficacy and the eradication of biofilm in cutaneous diseases still remains enigmatic. Hence, better understanding of their molecular biology, pathogenesis, and role in various diseases can help in the development of potential therapeutic strategies against biofilms in the future.

Quantify short-term outcomes associated with initial surgery [laparotomy (LAP) vs. peritoneal drain (PD)] for necrotizing enterocolitis (NEC) in extremely-low-birth-weight (ELBW) infants.Using the Children's Hospitals Neonatal Database, we identified ELBW infants32 weeks' gestation with surgical NEC (sNEC). Unadjusted and multivariable regression analyses were used to estimate the associations between LAP (or PD) and death/short bowel syndrome (SBS) and length of stay (LOS).LAP was the more common initial procedure for sNEC (n = 359/528, 68%). Infants receiving LAP were older and heavier. Initial procedure was unrelated to death/SBS in both bivariate (LAP: 43% vs PD: 46%, p = 0.573) and multivariable analyses (OR = 0.89, 95% CI = 0.57, 1.38, p = 0.6). LAP was inversely related to mortality (29% vs. 41%, p 0.007) in bivariate analysis, but not significant in multivariable analysis accounting for markers of preoperative illness severity. However, the association between LAP and SBS (14% vs. 5%, p = 0.012) remained significant in multivariable analyses (adjusted OR = 2.25, p = 0.039). LOS among survivors was unrelated to the first surgical procedure in multivariable analysis.ELBW infants who undergo LAP as the initial operative procedure for sNEC may be at higher risk for SBS without a clear in-hospital survival advantage or shorter hospitalization.Level II.

Multiple myeloma (MM) is a heterogeneous disease of the bone marrow (BM). Its association with Epstein-Barr virus (EBV) remains enigmatic. Aim of our study was to determine expression of latent membrane protein 1 (LMP1), aldehyde dehydrogenase 1 (ALDH1), CD117 and their association with 5-year survival in MM patients. Seven percent of cases expressed LMP1 in MM cells with no association with survival. Whereas, LMP1 expression in CD138- non-neoplastic cells was observed in 80% of the cases, conferring a survival advantage of 1.75 years (mean 3.75 ± 0.28, 95% CI 3.19-4.3). LMP1 in CD138- non-neoplastic cells was associated with CD117 expression in MM cells. Combinatorial analysis of LMP1 and CD117 stratified patients into good prognostic group LMP1+/CD117- (mean survival 4.16 ± 0.39 years) and a worst prognostic group; LMP1-/CD117+ (mean survival 1.02 ± 0.29 years). Our study showed that LMP1 expression in CD138- non-neoplastic cells of BM in MM patients confers a survival advantage.

OBJECTIVES Elevated pancreastatin (PST) levels have been shown to be associated with poor prognosis in small bowel neuroendocrine tumors (NETs). We hypothesized that plasma PST levels that remain elevated following surgical cytoreduction portend a poor prognosis in well-differentiated small bowel NETs. METHODS Patients diagnosed with small bowel NETs who underwent surgical cytoreduction at our institution were identified. Demographics, histopathologic characteristics, and biochemical data were collected. Only patients who had serial preoperative PST (PreopPST) and postoperative PST (PostopPST) levels were included in this study. Patients were sorted into groups by PST level to assess their response to surgical cytoreduction (group 1, PreopPST/PostopPST normal; group 2, PreopPST elevated/PostopPST normal; group 3, PreopPST/PostopPST elevated). Survival rates were calculated from the date of surgery. RESULTS PreopPST and PostopPST levels were collected from 300 patients. Patients in groups 1 (n = 74) and 2 (n = 81) had a significant survival advantage compared with patients in group 3 (n = 145) (P < 0.0001). Kaplan-Meier 5- and 10-year survival rates were as follows: group 1: 93% and 82%; group 2: 91% and 65%; and group 3: 58% and 34%, respectively. CONCLUSIONS Serial monitoring of plasma PST is useful in predicting long-term survival following surgical cytoreduction and can be helpful to identify patients who have a poor prognosis.

Objectives The aim of this study was to explore the time course of survival advantage of TAVR over SAVR as function of the patients' risk and sex. Background Women have been reported to have better survival than men undergoing transcatheter aortic valve replacement (TAVR). However, scant data on the sex-based survival benefit of TAVR over surgical aortic valve replacement (SAVR) are available. Methods A systematic review of studies reporting clinical outcomes of men and women undergoing TAVR or SAVR was performed. Studies were divided into two groups according to average patient's risk score and the interplay of surgical risk and sex on outcomes were analyzed. Results Eight studies involving 6,596 women and 7,204 men patients were extracted. Unlike mens, women patients had survival advantage from TAVR over SAVR that became substantial at 1 year from index procedure and persisted at 2-year of follow-up. Moreover, this sex-based TAVR survival advantage was mainly observed in higher surgical risk patients. Men showed a significantly lower rate of residual paravalvular leak after SAVR. Conclusions Women patients had a selective mortality benefit from TAVR compared to SAVR. This sex-based TAVR benefit was mainly observed in high surgical risk patients beyond 1 year from procedure.

Survival for patients with locally advanced esophageal cancer remains dismal. Non-response to neoadjuvant chemoradiation (nCRT) portends worse survival. We hypothesized that patients undergoing up-front esophagectomy may have better survival than those who do not respond to nCRT. We identified all patients undergoing esophagectomy with a pathologic stage of II or greater at our institution between 1994 and 2015 and separated them into two groups: those who received nCRT and those undergoing up-front esophagectomy. The neoadjuvant group was further separated into patients downstaged to pathologic stage 0 or I (responders) and patients with either the same or higher pathologic stage after nCRT, or with pathologic stage II disease or greater (non-responders). Overall survival was compared between groups using Kaplan–Meier statistics. Covariate-adjusted Cox modeling was used to estimate hazard ratios (HR) for mortality associated with non-response. Overall, 287 patients met inclusion criteria. Fifty-nine percent of the responders had pathologic complete response (pCR). The majority of non-responders and primary esophagectomy patients had stage II or III disease (94%). Median survival was 58.3 months in responders, 23.9 months in non-responders, and 29.1 months in primary esophagectomy patients (p

Overwintering brown marmorated stink bugs (Halyomorpha halys) (Stal) are a notable domestic nuisance. In addition to disruptive activity, dead individuals remain in homes, sometimes in large numbers. To better understand the effects of these remains on overwintering behavior, adult H. halys were subjected to several experiments to test their responses to dead conspecifics. In non-tactile tests of individuals exposed to groups of dead conspecifics, H. halys did not respond to 1-yr-old desiccated dead conspecifics, but avoided corpses that were freshly killed. In tactile tests of individuals exposed to groups of dead conspecifics, H. halys joined those corpse aggregations significantly more often than not, and preferred corpses to cotton when given a choice. In tests of exposure of overwintering individuals to fresh dead conspecifics over the course of a winter, no necrophagy or evidence of survival advantage was observed, but overall females had higher survival rates than males. USDA-NIFA SCRI award [2011-51181-30937, 2016-51181-25409] Apparatus construction was made possible by the Virginia Tech Myers-Lawson School of Construction. Insect collection assistance was provided by the Virginia Tech VIPR Lab. This research assistance was provided in part by the Virginia Tech BioBuild program, and by USDA-NIFA SCRI awards 2011-51181-30937 and 2016-51181-25409. Public domain – authored by a U.S. government employee

Objectives In the present study, we examine whether the relationships between country of origin or reason for migration and mortality differ between men and women. Methods We apply hazard regression models on high-quality Swedish register data with nationwide coverage. Results Relative to their Swedish counterparts, migrants from Nordic and East European (EU) countries and former Yugoslavia have higher mortality. This excess mortality among migrants relative to Swedes is more pronounced in men than in women. Migrants from Western and Southern European countries; Iran, Iraq, and Turkey; Central and South America; and Asia, have lower mortality than Swedes, and the size of the mortality reduction is similar in both sexes. The predictive effects of the reason for migration for mortality are also similar in migrant men and women. Conclusions This study provides little support for the hypothesis of a double survival advantage among immigrant women in Sweden. However, it does show that the excess mortality in migrants from Nordic and EU countries and former Yugoslavia relative to the Swedish-born population is more pronounced in men than in women. Electronic supplementary material The online version of this article (10.1007/s00038-019-01208-1) contains supplementary material, which is available to authorized users.

Purpose of review Kidney transplantation indisputably confers a significant survival advantage and a better quality of life compared with dialysis, however, because of the increasing demand for kidney transplantation many patients continue to wait prolonged periods for kidney transplantation. The first step to alleviate the shortage is to reduce the discard rate by utilizing more marginal kidneys. This review studied the recent literature on marginal kidney transplantation. Recent findings More than 60% of high-KDPI kidneys are discarded. Despite the increase in posttransplant costs, use of high KDPI transplants suggests a gain in survival years, thus making marginal kidney transplant cost effective. Furthermore, recent evidence suggests that marginal kidney transplantation shows a survival benefit compared with remaining in the waitlist and minimizes the kidney discard rate. Summary Transplantation with marginal kidneys provides a survival benefit over dialysis or waiting for a low-KDPI kidney. As a result, clinicians should strongly consider transplantation of marginal kidneys as opposed to waiting for a better offer.

Controlling hemorrhage has been a focus of survival since man recognized that the loss of blood led to death. Papyri from 1600 BCE describe methods for hemorrhage control including; direct pressure, ligature and the use of sutures. Multiple studies have demonstrated the survival advantage of early transfusion of whole blood or red cells and plasma. The added survival impact of early transfusion of platelets was recently reported in a substudy of the prospective Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial. Early transfusion of platelets demonstrated a statistically significant survival benefit at 24 h and 30 days post-injury. [1] Platelet availability is limited due to the short shelf life (5–7 days) and storage requirements (room temperature with constant agitation). Providing platelets or platelet derived products for prehospital treatment and to rural and some urban hospitals is an unmet medical need. The interest in novel and alternative platelet products has grown over the past decade and the status of novel platelet products is presented herein. Development, approval, and distribution of hemostatically effective approved platelet products for prehospital use and routine stockage in rural and urban centers could significantly increase survival rates in bleeding patients.

We aim to compare outcomes between loop ileostomy (LI) and total abdominal colectomy (TAC) for clostridium difficile infection (CDI) and hypothesize that LI is associated with fewer complications.The 2011-2016 ACS-NSQIP database was queried for patients undergoing LI or TAC for CDI. Patients with high outlying age, LOS, and operative time were excluded. Statistics were performed using IBM-SPSS and NCSS PASS-11.Of 457 patients identified, 47 underwent LI. Predicted morbidity was higher in the TAC cohort (62% vs. 37%, p 0.001). Patients in the LI cohort experienced fewer complications (72% vs. 87%, p = 0.021); however, mortality did not differ between LI (36%) and TAC (31%). Blood transfusions were more than twice as frequent in the TAC cohort (54% vs. 19%, p 0.001). Four patients in the LI cohort required reoperation; however, none required colectomy.No mortality difference was observed between LI and TAC. Prospective studies are required to determine the utility of LI.An analysis of the ACS-NSQIP database was performed and demonstrates that no survival benefit exists for patients who undergo loop ileostomy for C difficile infection compared to those who undergo total colectomy; however, patients who undergo loop ileostomy are likely to retain their colon with low risk of requiring subsequent colectomy.

We test whether relatively small US commercial banks that use traditional banking business models are more likely to survive during both good and bad economic climates. Our concept of bank survival is derived from Stigler (1958), and includes any bank that did not fail, was not acquired, and was not absorbed into its parent holding company. Our concept of traditional banking is based on four hallmark characteristics of this business model: Relationship loans, core deposit funding, revenue streams from traditional banking products and services, and physical bank branches. We find that banks that adhered more closely to this business strategy were an estimated 13 percentage points more likely to survive from 1997 through 2012 than banks that used less traditional business strategies. Importantly, the estimated traditional bank survival advantage approximately doubled during the 2006-2012 crisis period compared with the relatively stable 1997-2006 pre-crisis years.

The female survival advantage is incredibly robust, spanning almost all ages and societies in the past two centuries. While sociobehavioral factors account for part of the mortality differential, the female survival advantage extends beyond sex differences in risk-taking and aggression. Several physiological explanations have been proposed for broad protection against various chronic diseases and mortality in females, but much work remains to be done before we can fully understand how sex influences aging and longevity. Recent methods enable the disentanglement of classical gonadal steroid effects from those of sex chromosomes. Understanding the basis for sex differences in aging will ultimately lead to improved sex-specific therapies for increasing healthy longevity in both women and men.

Enterobactin (Ent), a prototypical bacterial siderophore known for its unparalleled affinity for iron, is widely conserved among members of the Enterobacteriaceae family of Gram-negative bacteria. ...

The transition from an industrial economy to an innovation economy poses two critical questions for the manufacturing sector in advanced countries. First, given the diffusion of modern manufacturing practices around the world, what level of innovation (incremental, more far-ranging, or radical) is most likely to support a resilient domestic manufacturing sector? Second, are assumed differences in the innovative capacity across space likely to hasten the decline of rural manufacturing? To answer these questions this research combines comprehensive measures of self-reported innovation able to reliably differentiate incremental and more far-ranging innovation with establishment-level data able to examine the geographical distribution of these different innovation strategies. The data used for the analysis includes a two-period panel of manufacturing establishments surveyed in 1996 and 2013 with annual employment data indicating survival in the intervening years. Our findings suggest that long-surviving manufacturing plants overwhelmingly gravitate away from non-innovation strategies toward incremental or more far-ranging innovation orientations. A survival advantage of far-ranging innovation over incremental innovation is observed for standalone firms. We do not identify a difference in the innovation orientations of rural and urban manufacturing establishments.

Summary The selective survival advantage of culture-adapted human embryonic stem cells (hESCs) is a serious safety concern for their clinical application. With a set of hESCs with various passage numbers, we observed that a subpopulation of hESCs at late passage numbers was highly resistant to various cell death stimuli, such as YM155, a survivin inhibitor. Transcriptome analysis from YM155-sensitive (YM155S) and YM155-resistant (YM155R) hESCs demonstrated that BCL2L1 was highly expressed in YM155R hESCs. By matching the gene signature of YM155R hESCs with the Cancer Therapeutics Response Portal dataset, BH3 mimetics were predicted to selectively ablate these cells. Indeed, short-course treatment with a sub-optimal dose of BH3 mimetics induced the spontaneous death of YM155R, but not YM155S hESCs by disrupting the mitochondrial membrane potential. YM155S hESCs remained pluripotent following BH3 mimetics treatment. Therefore, the use of BH3 mimetics is a promising strategy to specifically eliminate hESCs with a selective survival advantage., Graphical Abstract, Highlights • Culture-adapted hESCs against YM155/genotoxic agents mediated by high BCL-xL expression • Selective cell death of culture-adapted hPSCs by BH3 mimetics • Pluripotency maintenance of normal hESCs after exposure to BH3 mimetics, In this article, Cha and colleagues demonstrate that in culture-adapted hESCs, survival advantage toward several genotoxic stresses as well as YM155, a stemtoxic chemical, results from increased Bcl-xL expression. BH3 mimetics, predicted by a bioinformatics tool based on the gene expression signature of culture-adapted hESCs, induces selective cell death while normal hESCs remain functionally intact even after BH3 mimetics exposure.

Severe thrombocytopenia is a serious condition that frequently arises in patients with myelodysplastic syndrome (MDS) and is associated with poor prognosis. Few studies have investigated the prognostic significance of platelet recovery in patients with MDS having thrombocytopenia. We retrospectively analyzed 117 patients with de novo MDS complicated with thrombocytopenia (platelet count [PLT] < 100 × 109/L). Patients received decitabine treatment (schedule A) or decitabine followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT; schedule B). Severe thrombocytopenia (PLT < 20 × 109/L), identified in 31 (26.5%) patients, was associated with poor survival. The PLT increased significantly after decitabine treatment in the 2 groups. Patients with thrombocytopenia treated with schedule B showed a superior prognosis compared to those treated with schedule A. On analysis of overall survival by platelet response in patients with severe thrombocytopenia, a significant survival advantage was observed in patients who achieved a platelet response, who would further benefit from allo-HSCT following decitabine therapy. The results indicate a potentially favorable prognostic impact of platelet response achieved with decitabine. Patients with MDS having severe thrombocytopenia may benefit from the effective recovery of platelets and further allo-HSCT following decitabine therapy.

Gopher Tortoise (Gopherus polyphemus) populations are declining throughout the southeastern United States. Range-wide conservation efforts include identifying populations that do not currently meet viability criteria but are suitable candidates for population enhancement. We investigated the potential role of head starting as a recovery tool by releasing hatchling and head-started yearling Gopher Tortoises as pairs (n = 28) into adult burrows in fall and comparing their movements and survival until winter dormancy. Head-started yearlings experienced higher predicted survival than did hatchlings (87.7% vs. 56.5%). Head-started individuals also tended to move greater distances between burrows and established dormancy burrows further from their release burrows, but the differences were not significant. Most individuals of both groups used a small number of closely spaced burrows, although hatchlings took longer than head-started individuals to establish their first burrow (11.3 vs. 4.4 d on average) and a higher proportion were depredated or censored before establishing a burrow (35.7% vs. 10.7%). The paired release design provides strong experimental evidence that head-started yearling Gopher Tortoises experience at least a short-term survival advantage over hatchlings, while exhibiting comparable fidelity to the release site. Soft-release pens were not necessary to promote high site fidelity in our study, but the decision as to whether or not to use them at other release sites may be dictated by the predator community and what is practical to implement. We contend that head starting shows promise as a recovery tool for Gopher Tortoises and that hard releases may be a worthwhile option for managers to consider.

Simple Summary Upfront genetics/cytogenetics and minimal measurable disease (MRD) are becoming relevant biomarkers in the process of post-remission transplant allocation in AML. However, until recently the transplantation choice relied on the availability of a fully matched familiar donor, whereas individual patient- and disease-related characteristics played a secondary role in transplant allocation. In this paper we analyzed the evolution of the transplantation policy at our center in a 20-year time interval. At the beginning of our observation patients were submitted to allogeneic transplant, per protocol, mostly if a fully matched family donor was available or to autologous transplant if no fully matched family donor was identified (“donor vs. no donor” strategy) regardless of upfront genetics/cytogenetics or MRD status. Thereafter, persistence of MRD after consolidation cycle was included in the decision-making process for transplant selection. Patients with favorable and intermediate-risk cytogenetic risk were to receive allogeneic or autologous stem cell transplantation if MRD positive or negative, respectively, (“transplant vs. no transplant” strategy). In this cohort, patients with FLT3-ITD or adverse risk karyotype were submitted to allogeneic transplant as well. Abstract Measurable residual disease (MRD) is increasingly employed as a biomarker of quality of complete remission (CR) in intensively treated acute myeloid leukemia (AML) patients. We evaluated if a MRD-driven transplant policy improved outcome as compared to a policy solely relying on a familiar donor availability. High-risk patients (adverse karyotype, FLT3-ITD) received allogeneic hematopoietic cell transplant (alloHCT) whereas for intermediate and low risk ones (CBF-AML and NPM1-mutated), alloHCT or autologous SCT was delivered depending on the post-consolidation measurable residual disease (MRD) status, as assessed by flow cytometry. For comparison, we analyzed a matched historical cohort of patients in whom alloHCT was delivered based on the sole availability of a matched sibling donor. Ten-years overall and disease-free survival were longer in the MRD-driven cohort as compared to the historical cohort (47.7% vs. 28.7%, p = 0.012 and 42.0% vs. 19.5%, p = 0.0003). The favorable impact of this MRD-driven strategy was evident for the intermediate-risk category, particularly for MRD positive patients. In the low-risk category, the significantly lower CIR of the MRD-driven cohort did not translate into a survival advantage. In conclusion, a MRD-driven transplant allocation may play a better role than the one based on the simple donor availability. This approach determines a superior outcome of intermediate-risk patients whereat in low-risk ones a careful evaluation is needed for transplant allocation.

Purpose To assess the effect of race/ethnicity in cancer-specific mortality (CSM) adjusted for other-cause mortality (OCM) in metastatic prostate cancer patients (mPCa) treated with external beam radiotherapy (EBRT) to the prostate. Methods We relied on the Surveillance, Epidemiology, and End Results (SEER) database to identify Caucasian, African-American, Hispanic/Latino and Asian mPCa patients treated by EBRT between 2004 and 2016. Cumulative incidence plots displayed CSM after adjustment for OCM according to race/ethnicity. Propensity score matching accounted for patient age, prostate-specific antigen, clinical T and N stages, Gleason Grade Groups and M1 substages. OCM adjusted multivariable analyses tested for differences in CSM in African-Americans, Hispanic/Latinos and Asians relative to Cauacasians. Results After 3:1 propensity score matching and OCM adjustment, Asians exhibited lower CSM at 60 and 120 months (48.2 and 60.0%, respectively) compared to Caucasians (66.7 and 79.4%, respectively, p p Conclusion In the setting of mPCa treated with EBRT, Asians exhibit lower CSM than Caucasians, African-Americans and Hispanic/Latinos. This observation may warrant consideration in prognostic stratification schemes for newly diagnosed mPCa patients.

Stereotactic radiosurgery (SRS) has been utilized broadly for brain metastases not only for intact ones but as well as of late for the postoperative cavity of metastases after surgery, due to the advantages of SRS to preserve neurocognitive functions, maintain local control and prescribe the treatment in a short time frame. Randomized trials have proven the safety and efficacy of cavity SRS compared to observation. As WBRT offers no survival advantage in comparison to SRS and frequent monitorization with brain MRIs for early salvage upon failure, there has been a revolution in clinical approach for patients with limited intact brain metastases to treat with SRS only and omit WBRT. The recent implementation of the PO-SRS applications to the treatment algorithm of resected BMs has reputably enhanced the local control at the surgical resection bed in comparison to observation or WBRT Likewise, the postoperative cavity SRS for brain metastases has gained a growing reputation. In this review, we summarize the proof for evidence-based optimization in the postoperative setting of the surgically removed brain metastases.

Melanoma is one of the highly immunogenic malignancies, and histological regression (HR) and tumor infiltrating lymphocytes (TILs) represent early signs of activation of the immune system against primary melanoma. In this study we aimed to investigate the potential roles of HR and TILs on survival, as combined or separately. A total of 916 cutaneous melanomas were analyzed retrospectively. Only minority of the lesions had HR (25.1%) and they were associated with males (p = 0.002), axial localization (p = 0.0001), non-nodular histopathology (p = 0.0001), thin Breslow depth (p = 0.01) and nevus-associated melanoma (p = 0.03). Those with TILs (48.4%) were found in association with lower Clark levels (p = 0.003), thin tumor thicknesses (p = 0.001), lower mitotic rates (p = 0.02), BRAF mutation (p = 0.03), absence of neurotropism (p = 0.03), involvement of lymph node (p = 0.0001) and relapse of disease (p = 0.04). A significant relationship was found between HR and TILs (p = 0.01). TILs were independently associated with favorable RFS (p = 0.02), whereas no relationship was observed between HR and RFS (p = 0.2). A marked favorable survival advantage was noted in the group with HR (+)/TILs (+) compared to other groups with HR (−)/TILs (−) (p = 0.007), only HR (+) and only TILs (+). Both HR (p = 0.05) and TILs (p = 0.04) were correlated with favorable OS rates. Moreover, HR (+) /TILs (+) patients had more favorable OS than other groups with HR (−)/TILs (−) (p = 0.002), only HR (+) and only TILs (+). Only HR (+) and only TILs (+) subgroups separately were found to be associated with favorable survivals in melanoma. Furthermore, coexistence of HR and TILs, HR (+)/TILs (+) subgroup, had more favorable survival rates compared to only HR (+) and only TILs (+) subgroups.

Background: Despite the survival advantage, not all metastatic renal cell carcinoma (mRCC) patients achieve a long-term benefit from immunotherapy. Moreover, the identification of prognostic biomarkers is still an unmet clinical need. Methods: This multicenter retrospective study investigated the prognostic role of peripheral-blood inflammatory indices and clinical factors to develop a novel prognostic score in mRCC patients receiving at least second-line nivolumab. The complete blood count before the first cycle of therapy was assessed by calculating neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and systemic inflammation response index (SIRI). Clinical factors included pre-treatment International Metastatic RCC Database Consortium (IMDC) score, line of therapy, and metastatic sites. Results: From October 2015 to November 2019, 571 mRCC patients received nivolumab as second- and further-line treatment in 69% and 31% of cases. In univariable and multivariable analyses all inflammatory indices, IMDC score, and bone metastases significantly correlated with overall survival (OS). The multivariable model with NLR, IMDC score, and bone metastases had the highest c-index (0.697) and was chosen for the developing of the score (Schneeweiss scoring system). After internal validation (bootstrap re-sampling), the final index (Meet-URO score) composed by NLR, IMDC score, and bone metastases had a c-index of 0.691. It identified five categories with distinctive OSs: group 1 (median OS – mOS = not reached), group 2 (mOS = 43.9 months), group 3 (mOS = 22.4 months), group 4 (mOS = 10.3 months), and group 5 (mOS = 3.2 months). Moreover, the Meet-URO score allowed for a fine risk-stratification across all three IMDC groups. Conclusion: The Meet-URO score allowed for the accurate stratification of pretreated mRCC patients receiving nivolumab and is easily applicable for clinical practice at no additional cost. Future steps include its external validation, the assessment of its predictivity, and its application to first-line combinations.

Rationale and Objectives Patients with hepatic metastases from colorectal cancer have a poor prognosis in the salvage setting. This study assessed the survival benefit of adding transarterial 90Y radioembolization in the salvage setting to systemic therapy. Materials and Methods In this retrospective, matched-pair study, 21 patients who underwent radioembolization plus systemic therapy were matched with a cohort of 173 patients who received systemic chemotherapy alone in the salvage setting, defined as progression on at least two different regimens of systemic chemotherapy. Patients were matched one-to-one on Eastern Cooperative Oncology Group Performance Status, presence of extrahepatic disease, and presence of tumor KRAS mutation. Radioembolization patients underwent treatment using standard dosimetry to either a hepatic lobe or the whole liver. Survival data was analyzed using Kaplan-Meier analysis. Results Patients who underwent radioembolization plus systemic therapy vs. those who had systemic therapy alone had similar demographics and exposure to prior systemic chemotherapies. Median survival from the date of primary diagnosis was 38 (95% CI 26 to 50) v 25 (95% CI 15 to 35) months in radioembolization with systemic therapy vs. systemic therapy alone (p = 0.17). Median survival from the date of hepatic metastases was 31 (95% CI 23.8 to 38.2) v 20 months (95% CI 10.2 to 29.8) in radioembolization with systemic therapy vs. systemic therapy alone (p = 0.03). Conclusion The addition of radioembolization to systemic therapy in patients with metastatic colorectal cancer to the liver may improve survival in the salvage setting.

Background and Purpose: A survival advantage among individuals with higher body mass index (BMI) has been observed for diverse acute illnesses, including stroke, and termed the obesity paradox. However, prior ischemic stroke studies have generally tested only for linear rather than nonlinear relations between body mass and outcome, and few studies have investigated poststroke functional outcomes in addition to mortality. Methods: We analyzed consecutive patients with acute ischemic stroke enrolled in a 60-center acute treatment trial, the NIH FAST-MAG acute stroke trial. Outcomes at 3 months analyzed were (1) death; (2) disability or death (modified Rankin Scale score, 2–6); and (3) low stroke-related quality of life (Stroke Impact Scale Results: Among 1033 patients with acute ischemic stroke, average age was 71 years (±13), 45.1% female, National Institutes of Health Stroke Scale 10.6 (±8.3), and BMI 27.5 (±5.6). In both unadjusted and adjusted analysis, increasing BMI was linearly associated with improved 3-month survival ( P =0.01) odds ratios in adjusted analysis for mortality declined across the BMI categories of underweight (odds ratio, 1.7 [CI, 0.6–4.9]), normal (odds ratio, 1), overweight (0.9 [CI, 0.5–1.4]), obese (0.5, [CI, 0.3–1.0]), and severely obese (0.4 [CI, 0.2–0.9]). In unadjusted analysis, increasing BMI showed a U-shaped relation to poststroke disability or death (modified Rankin Scale score, 2–6), with odds ratios of modified Rankin Scale score, 2 to 6 for underweight, overweight, and obese declined initially when compared with normal weight patients, but then increased again in severely obese patients, suggesting a U-shaped or J-shaped relation. After adjustment, including for baseline National Institutes of Health Stroke Scale, modified Rankin Scale score 2 to 6 was no longer related to adiposity. Conclusions: Mortality and functional outcomes after acute ischemic stroke have disparate relations with patients’ adiposity. Higher BMI is linearly associated with increased survival; and BMI has a U-shaped or J-shaped relation to disability and stroke-related quality of life. Potential mechanisms including nutritional reserve aiding survival during recovery and greater frequency of atherosclerotic than thromboembolic infarcts in individuals with higher BMI.

Visceral obesity and systemic inflammatory response (SIR) were suggested to be closely related to colon cancer (CC) oncological and surgical outcomes. The first by producing several soluble factors involved in carcinogenesis and the second for having a key role in the nutritional and functional decline of patients with cancer. Furthermore, gender differences in relative body composition and adipose tissue regional distribution have also been acknowledged to influence CC. The primary aim of this study was to determine whether visceral adiposity, stratified by gender, influenced CC staging and prognosis. As secondary aim, this study evaluated whether visceral adiposity and SIR markers were associated with CC pathological features so that these could be used in clinical practice to predict disease outcomes and potentially influence therapeutic decisions. Case records from patients (n = 300) submitted to CC surgical resection at a single tertiary hospital were retrospectively reviewed to retrieve clinical, laboratory, imaging and pathological data. Visceral fat area was quantified by computerized morphometric analysis in preoperative tomography scans. Visceral obesity was defined as visceral fat area ≥160 cm2 for men and ≥80 cm2 for women. Preoperative full blood count performed as part of the routine clinical assessment at the hospital laboratory was used to obtain C-reactive protein (CRP) levels and to calculate neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), which were used as SIR markers. One hundred and forty-three (n = 143) patients fulfilled eligibility criteria and were included in the analysis. Patients with high-visceral adipose tissue (vAT) had smaller size CC tumors (p < 0.001), earlier T-stage disease (p = 0.027) and lower nodal involvement (p = 0.039). In gender subgroup analysis, these findings were only confirmed in males. Moreover, male patients with high-vAT also had a lower proportion of metastatic nodes (p = 0.021) and metastatic to dissected lymph node ratio (p = 0.030). Additionally, patients with high-vAT also had lower PLR (p = 0.001). CC survival was not influenced by visceral obesity, gender nor SIR. In conclusion, our study shows that male patients with high visceral adiposity have lower PLR levels and earlier stage tumors. Furthermore, our data suggests that visceral obesity and SIR despite being associated with earlier stage CC tumors do not seem to present a survival advantage.

Background. A female prognostic advantage in younger individuals has been demonstrated in various cancers. Several large-scale analyses based on different racial backgrounds have reported inconsistent results in colorectal cancer. The aim of the present study was to evaluate the prognostic value of sex and age in patients with colorectal cancer of different ethnic groups. Methods. We identified 71,812 eligible patients from the Surveillance, Epidemiology and End Results database. According to age at diagnosis, the patients were categorized into premenopausal age (≤45 yrs), menopausal age (46–54 yrs), and postmenopausal age (≥55 yrs) subgroups for further analysis. Results. Multivariate analysis identified the female survival advantage to be significant in the premenopausal age subgroup ( P = 0.002 , HR (95% CI): 0.73 (0.60–0.89)), diminished in the menopausal age subgroup ( P = 0.09 ), and absent in the postmenopausal age subgroup ( P = 0.96 ). Furthermore, the female survival advantage at premenopausal age was significant only in white patients ( P = 0.001 , HR (95% CI): 0.68 (0.54–0.87)) and not in either American Indian/Alaska Native or Asian or Pacific Islander patients. There was a trend of better survival of females in black patients ( P = 0.07 ). Conclusions. Sex was a major prognostic factor in colorectal cancer patients, especially premenopausal women, and the difference was also associated with race.

Although surgical resection of the solid tumor component of glioblastoma has been shown to provide a survival advantage, it will never be a curative procedure. Yet, systemically applied adjuvants (radiation therapy and chemotherapy) also are not curative and their options are limited by the inability of most agents to cross the blood-brain barrier. Direct delivery of adjuvant therapies during a surgical procedure potentially provides an approach to bypass the blood-brain barrier and effectively treat residual tumor cells. This article summarizes the approaches and therapeutics that have been evaluated to date, and challenges that remain to be overcome.

Background We hypothesize that women undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis from appendiceal cancer will have a survival advantage compared to men. Methods The National Cancer Database (NCDB) public user file (2004–2014) was used to select patients with PC undergoing CRS and HIPEC from appendiceal cancer. Univariate and multivariable analyses were performed. Results 1,190 patients with PC from appendiceal cancer underwent HIPEC and CRS. OS was significantly longer for women than for men, with mean and median OS being 73.8 months and 98.2 months for women vs 58.7 months and 82.5 months for men, respectively (p = 0.0032). On multivariable analysis, male sex (HR: 1.444, 95% CI: 1.141–1.827, p = 0.0022) and increasing age (HR: 1.017, 95% CI: 1.006–1.027, p = 0.0017) were both found to be independent risk factors for worse OS. Conclusion Women undergoing CRS and HIPEC for PC from appendiceal origin live longer than men undergoing the same treatment. Increasing age was also found to be independent risk factors for worse survival

Introduction Level 1 evidence from randomised trials demonstrates less complication when jaundiced patients with resectable pancreatic cancer proceed directly to surgery, rather than undergo preoperative biliary drainage (PBD) first. Although ‘fast track’ surgery significantly increases the resectability rate, it is unknown whether this translates into a survival benefit. This study evaluated the effect of upfront surgery on long-term survival using an intention-to-treat (ITT) analysis. Methods Patients were identified from a prospectively maintained database, stratified according to whether or not they underwent PBD. Results Among 157 patients, 84 (54%) underwent PBD. Of these, 73% underwent surgery, compared to 100% of those without PBD (p

A consistent finding from contemporary Western societies is that women outlive men. However, what is unclear is whether sex differences in survival are constant across varying socio-ecological conditions. We test the universality of the female survival advantage with mortality data from a nineteenth century population in the Baja California peninsula of Mexico. When examined simply, we find evidence for a male-biased survival advantage. However, results from Cox regression clearly show the importance of age intervals for variable survival patterns by sex. Our key findings are that males: (i) experience significantly lower mortality risk than females during the ages 15–30 (RR = 0.69), (ii) are at a significantly increased risk of dying in the 61+ category (RR = 1.30) and (iii) do not experience significantly different mortality risk at any other age interval (0–14, 31–45, 46–60). We interpret our results to stem from differing intrinsic and extrinsic risk factors for sex-biased mortality across age intervals, highlighting the relevance of a lifecourse approach to the study of survival advantage. Ultimately, our results make clear the need to more broadly consider variability in mortality risk factors across time and place to allow for a clearer understanding of human survival differences.

Mexican immigrants enjoy a substantial mortality advantage over non-Hispanic whites in the US, although their health declines with greater duration of residence. Many previous studies have suggested this advantage reflects higher levels of social support among Mexicans in enclave communities with high co-ethnic density. As the Mexican-origin population in the US has grown, it has expanded outside traditional gateway cities in California and Texas to new destinations throughout the US, and it has become increasingly important to understand how settlement in new destinations impacts the health of Mexican immigrants. This study examines the mortality outcomes of Mexican immigrants in Traditional Gateways versus New and Minor Destinations in the US. Using a nationally-representative survey with mortality follow-up the analysis finds that Mexican immigrants in new and minor destinations have a significant survival advantage over their counterparts in traditional gateways. This advantage largely reflects the mortality benefits of living in communities with smaller and less-established Mexicans immigrant communities, a finding that runs in contrast to prior work on the protective effects of immigrant enclaves. The results suggest that future research must reevaluate the relationship between neighborhood ethnic composition, social support, and immigrant health.

The prognosis of brain metastases (BM) is traditionally poor. BM are mainly treated by local radiotherapy, including stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT). Recently, immunotherapy (i.e., immune checkpoint inhibitors, ICI) has demonstrated a survival advantage in multiple malignancies commonly associated with BM. Individually, radiotherapy and ICI both treat BM efficiently; hence, their combination seems logical. In this review, we summarize the existing preclinical and clinical evidence that supports the applicability of radiotherapy as a sensitizer of ICI for BM. Further, we discuss the optimal timing at which radiotherapy and ICI should be administered and review the safety of the combination therapy. Data from a few clinical studies suggest that combining SRS or WBRT with ICI simultaneously rather than consecutively potentially enhances brain abscopal-like responses and survival. However, there is a lack of conclusion about the definition of "simultaneous"; the cumulative toxic effect of the combined therapies also requires further study. Thus, ongoing and planned prospective trials are needed to further explore and validate the effect, safety, and optimal timing of the combination of immunotherapy with radiotherapy for patients with BM.

Attributable to the high likelihood of developing distant metastatic disease, resection of poorly differentiated gastroenteropancreatic neuroendocrine neoplasms is generally contraindicated. Some patients with no distant metastatic disease will nonetheless undergo surgical resection and their outcomes are not known. We aimed to determine whether surgery confers survival advantage over systemic therapy alone for patients with non-metastatic poorly differentiated gastroenteropancreatic neuroendocrine neoplasms.We performed a retrospective cohort study (2000-2012) of adults in the California Cancer Registry who had poorly differentiated gastroenteropancreatic neuroendocrine neoplasms (World Health Organization Grade 3) and no clinical evidence of distant metastasis (M0). Patients who underwent surgery were compared with those managed non-operatively. The adjusted Cox proportional hazards model was used to assess the risk of death.Among 2,245 patients (45% female, 21% pancreatic, 79% gastrointestinal), 1,549 (69%) were treated with surgery, and 696 (31%) received either systemic therapy or palliative measures alone. Median survival was 31 months after surgery versus 9 months after non-operative therapy (log-rank test, P.001). Rates of 5-year overall survival were 39% after surgery versus 10% in the non-operative group. Adjusting for age, sex, comorbidities, receipt of chemotherapy, and tumor size and location, patients treated with surgery had a 58% lower likelihood of death compared with non-operative therapy (hazard ratio: 0.42, 95% confidence interval: 0.36-0.50, P.001). Restricting our results to those patients who were found to have no distant metastasis intraoperatively (ie, pathologically M0), 5-year survival after surgery reached 44%.While poorly differentiated gastroenteropancreatic neuroendocrine neoplasms carries a poor prognosis, for patients with no evidence of metastatic disease, resection appears to confer significant improvement in long-term survival. Although caution and an individualized approach in treating poorly differentiated gastroenteropancreatic neuroendocrine neoplasms is advised, future guidelines might reflect this survival advantage.

Due to the natural selection pressure, certain aspects of memory may have been selected to give humans a survival advantage. Research has demonstrated that processing information for survival relevance leads to better item memory (i.e., the content of information) compared to control conditions. The current study investigates the effects of survival processing on context memory (i.e., memory for peripheral episodic details) and item memory to better understand when the survival processing memory advantage emerges. In this study, participants studied pictures of objects in either a survival or moving (control) condition. Objects were presented in either a plausible color, for example, a red apple, or in an implausible color, such as a green pie. We chose this color plausibility manipulation because color is a detail that conveys information about the fitness (and other diagnostic information) about an item. After studying items, participants made item memory judgments (did you see this item before?) and two context memory judgments: color context (in which color did you see this item?) and source context (in which condition did you see this item?). Results indicated better item memory for materials processed in the survival relative to moving condition. Critically, for color context, there was a condition by plausibility interaction, where memory was best for plausibly colored items in the survival processing condition. There was no difference, however, in source context memory between the survival and moving conditions. These results suggest the survival processing memory advantage extends to contextual details that particularly reflect the survival utility of items such as color.

Background: Prior studies evaluating diet quality in relation to ovarian cancer survival are sparse, and to date none have assessed diet quality or diet-quality change after diagnosis. Methods: In the prospective Ovarian cancer Prognosis And Lifestyle (OPAL) study, diet-quality scores were calculated using data from food frequency questionnaires completed pre-diagnosis (n = 650) and 12 months' post-diagnosis (n = 503). We used Cox proportional hazard models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association between diet quality and survival. Results: During the median follow-up of 4.4 years, 278 women died from ovarian cancer. There was no evidence of an association between diet quality pre- or post-diagnosis and progression-free, overall, or ovarian cancer–specific survival. No survival advantage was observed for women who had either improved their diet quality or who consumed a high-quality diet both before and 12 months after diagnosis. Conclusions: Higher pre- and post-diagnosis diet quality was not associated with better survival outcomes in this cohort of women with ovarian cancer. Impact: Diet quality is important for a range of health outcomes but may not improve survival after a diagnosis of ovarian cancer.

A hypercoagulable state has been described in coronavirus disease 2019 (COVID-19) patients. Others have reported a survival advantage with prophylactic anticoagulation (pAC) and therapeutic anticoagulation (tAC), but these retrospective analyses have important limitations such as confounding by indication. We studied the impact of tAC and pAC compared with no anticoagulation (AC) on time to death in COVID-19. We performed a cross-sectional analysis of 127 deceased COVID-19 patients and compared time to death in those who received tAC (n = 67), pAC (n = 47), and no AC (n = 13). Median time to death was longer with higher doses of AC (11 days for tAC, 8 days for pAC, and 4 days for no AC, p

ObjectiveTo evaluate differences in morbidity and mortality among mechanically ventilated patients with COVID-19 treated with therapeutic versus prophylactic anticoagulation.MethodsWe performed a retrospective review of 245 COVID-19 positive patients admitted to the ICU requiring mechanical ventilation from March 1, 2020 through April 11, 2020 at Mount Sinai Hospital. Patients either received therapeutic anticoagulation for a minimum of 5 days or prophylactic dose anticoagulation. Morbidity and mortality data were analyzed.ResultsPropensity score (PS) weighted Kaplan-Meier plot demonstrated a survival advantage (57% vs. 25%) at 35 days from admission to the ICU in patients who received therapeutic anticoagulation for a minimum of 5 days compared to those who received prophylactic anticoagulation during their hospital course. A multivariate Cox proportional hazard regression model with PS weights to adjust for baseline differences found a 79% reduction in death in patients who were therapeutically anticoagulated HR 0.209, [95% Cl (0.10, 0.46), p < 0.001]. Bleeding complications were similar between both groups. A 26.7% [95% Cl (1.16, 1.39), p< 0.001] excess mortality was found for each 1 mg/dL rise in serum creatinine over a 21-day period.ConclusionsTherapeutic anticoagulation is associated with a survival advantage among patients with COVID-19 who require mechanical ventilation in the ICU.

Group living is predicted to arise only when the fitness benefits outweigh the costs of sociality. Group-living species-including cooperatively breeding and family-living birds and mammals-occur most frequently in environments where climatic conditions fluctuate unpredictably from year to year. The fitness consequences of group living are thus expected to vary with changing environmental conditions, though few studies have examined this possibility. We examined whether living in large social groups improves adult survivorship in cooperatively breeding superb starlings (Lamprotornis superbus). We also tested the hypothesis that larger groups buffer against harsh conditions by increasing survivorship most under periods of low rainfall. We found that group size was positively correlated with adult survival but in a sex-specific manner: female survival increased with group size across all environmental conditions, whereas male survival increased with group size only in wet years. Together with previous work in this system, our results suggest that larger groups confer survival benefits by reducing predation, rather than by improving access to food or buffering against physiological stress. Although group living does not appear to buffer against harsh conditions in adult starlings living in a fluctuating environment, living in larger groups does confer a survival advantage.

INTRODUCTION AND OBJECTIVE:Previous studies have shown a survival advantage for patients with high body mass index (BMI) and metastatic renal cancer. In prostate cancer patients, findings regarding...

Animate items are better remembered than inanimate items, suggesting that human memory has evolved to prioritize information related to survival. The proximate mechanisms for the animacy effect are not yet known, but one possibility is that animate items are more likely to capture attention, which then leads to better memory for those items. The first experiment independently manipulated the animacy and perceived threat of studied items and found that both target recognition and false-alarm recognition were higher for animate items compared to inanimate items and for threatening items compared to non-threatening items. The effects were eliminated when d' scores were calculated. The second experiment used a response signal delay (RSD) manipulation where participants were forced to respond after a short (500 ms) or long (2,000 ms) time delay during the recognition test. Similar to the first experiment, the effects of animacy and threat for target recognition and false-alarm recognition persisted and did not interact with the RSD manipulation. Taken together, the results of the studies suggest that the animacy and threat effects in memory are robust and that attention capture might be at least partly responsible for the animacy effect.

In The BMJ five years ago my colleagues and I questioned the appropriateness of a policy of early detection of colorectal metastases for surgical resection.1 We now have direct evidence from a randomised controlled trial (RCT) that any survival advantage from resection of colorectal lung metastases is, in all likelihood, very much smaller than has been assumed.2 There have been many uncontrolled reports of lung metastasectomy with five year survival of around 40%,3 a figure matched in the Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) trial (38%, 95% confidence interval 23% to 62%).2 …

Background: Recently, the CARMENA and SURTIME studies, suggested that upfront cytoreductive nephrectomy (CN) should be abandoned for patients with intermediate and high-risk metastatic renal cell carcinoma (mRCC). However, CN remains an indication in low-risk and when immediate systemic treatment is not required. The aim was to evaluate the long-term overall survival (OS) in patients with primary mRCC, based on the first line treatment. Methods: There were 1483 patients with primary mRCC in the National Kidney Cancer Registry from 2005 to 2013. Data on primary treatment, TNM stage, RCC type, tumor size, patient age and sex were extracted. Survival time was calculated from time of diagnosis to time of death or until July 2019. Mann-Whitney U and Chi-square tests, the Kaplan-Meyer method and Cox regression analyses were used. Results: Patients primary treated with CN had a significantly longer OS (p

Loci associated with longevity are likely to harbor genes coding for key players of molecular pathways involved in a lifelong decreased mortality and decreased/compressed morbidity. However, identifying such loci is challenging. One of the most plausible reasons is the uncertainty in defining long‐lived cases with the heritable longevity trait among long‐living phenocopies. To avoid phenocopies, family selection scores have been constructed, but these have not yet been adopted as state of the art in longevity research. Here, we aim to identify individuals with the heritable longevity trait by using current insights and a novel family score based on these insights. We use a unique dataset connecting living study participants to their deceased ancestors covering 37,825 persons from 1,326 five‐generational families, living between 1788 and 2019. Our main finding suggests that longevity is transmitted for at least two subsequent generations only when at least 20% of all relatives are long‐lived. This proves the importance of family data to avoid phenocopies in genetic studies., In this study we show that human longevity is transmitted for at least 2 subsequent generations only when at least 20% of a person’s relatives are long‐lived. The analyses are based on a unique dataset, covering 37,825 persons from 1,326 five‐generational families, in which living study participants are connected to their deceased ancestors. Our findings highlight the importance of using survival information of relatives/ancestors to avoid long‐lived phenocopies in genetic studies and aim to stimulate cohort studies to extend their data with such ancestral information.