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IntroductionPatients suffering from advanced heart failure may undergo left ventricular assist device (LVAD) placement as a bridge to cardiac transplantation. However, those with a BMI above 35 kg/m2 are generally not considered eligible for transplant due to their elevated cardiac risk. We review our experience with bariatric surgery in this high-risk population to assess its safety and efficacy in reducing BMI to permit cardiac transplantation.MethodsWe retrospectively reviewed all patients on durable LVAD support who underwent sleeve gastrectomy (SG) at Mount Sinai Hospital between August 2018 and December 2022. Electronic medical records were reviewed to analyze patient demographics, surgical details, and outcomes regarding weight loss and heart transplantation.ResultsWe identified twelve LVAD patients who underwent SG. Three were performed laparoscopically and 9 via robotic approach. Four patients (33.3%) underwent an orthotopic heart transplant (OHTx). Half of these patients were female. For patients who underwent OHTx, mean age at LVAD placement was 41.0 (R30.6–52.2), at SG was 43.9 (R32.7–55.0) and at OHTx was 45.3 years (R33.3–56.8). Mean BMI increased from 38.8 at LVAD placement to 42.5 prior to SG. Mean time from SG to OHTx was 17.9 months (R6-7-27.5) during which BMI decreased to mean 32.8 at the time of OHTx. At most recent follow-up, mean BMI was 31.9. All patients were anticoagulated prior to surgery; one required return to the operating room on post-operative day 1 after SG for bleeding and one was re-admitted on post-operative day 7 for hematochezia treated conservatively.ConclusionSG is a safe and effective operation in patients with severe obesity and heart failure requiring an LVAD. 66.7% of our cohort achieved target BMI < 35 and 33.3% underwent heart transplantation. Longer term follow-up is needed to clarify full bridge-to-transplant rate and long-term survival outcomes.

Left ventricular assist device (LVAD)–specific infections (LSIs) are common in patients on LVAD support awaiting heart transplant (HT), yet their impact on post-HT outcomes is not completely understood. We hypothesized that LSIs would result in vasoplegia and negatively affect post-HT 30-day and 1-year outcomes. LSI was defined as driveline, pump, or pocket infection. The short-term outcome was a composite of acute renal failure, allograft rejection, and mortality at 30 days after HT. The long-term outcome was a composite of allograft rejection and death within 1 year after HT. We performed a retrospective analysis of 111 HT recipients bridged with durable LVAD support at our institution from May 2012 to August 2019. Of these, 63 patients had LSIs, with 94% of the infections being driveline infections. Vasoplegia was more prevalent in the LSI group but not significantly (7 vs 2 persons, p = 0.3). There was no difference in the composite end point of acute renal failure, rejection, or death at 30 days (30% vs 25%, p = 0.55) or 1-year end point of rejection and death (38% vs 40%, p = 0.87) in patients with LSI versus those without LSI. In conclusion, LSIs were common in patients on LVAD who underwent HT in our single-center contemporary cohort. However, LSI was not associated with adverse outcomes at 30 days or at 1 year after HT.

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There is considerable variability in how older adults with cancer tolerate and recover from surgery and systemic treatments. A greater understanding of individual trajectories is crucial in guiding personalized treatment decisions. Frailty may explain these inter-individual differences. Despite emerging evidence on the association between perioperative frailty assessment and outcomes after noncardiac surgery, there is limited data in gynecologic oncology. A perioperative cardiovascular risk assessment, recommended by scientific guidelines, is widely adopted in noncardiac surgery, often as the only standardized perioperative risk stratification approach. While based on robust evidence on the association with cardiovascular complications and overall mortality, it might be insufficient to predict other essential surgical, oncologic and patient-important outcomes. The FARGO study is a multi-centre prospective cohort study targeting 280 patients aged 55 or older undergoing surgery, with or without chemotherapy, for a suspected or confirmed gynecologic malignancy. The primary objective is to evaluate the predictive value of the Frailty Phenotype measured preoperatively, compared with the currently used perioperative risk assessment (cardiovascular risk assessment based on the Revised Cardiac Risk Index, age, and occurrence of myocardial injury after non-cardiac surgery) in predicting the composite outcome of all-cause death or new disability at six months after surgery. Secondary objectives include comparing the predictive value of the Frailty Phenotype with that of the Clinical Frailty Scale; evaluating the performance of a preoperative frailty assessments on other postoperative complications, chemotherapy tolerance, and 1-year recurrence-free survival; exploring the added predictive value of a dynamic perioperative frailty assessment repeated 28 days after surgery; assessing the acceptability of frailty assessments by physicians and patients; and establishing a biobank to investigate frailty biomarkers. The findings could have important implications for risk stratification, planning and tailoring surgical and oncologic care for older adults with gynecologic malignancies. Our study emphasizes patient-centered outcomes and stakeholders' perspectives. Trial registration: Clinicaltrials.gov Identifier: NCT05738252.

Non-technical summaryResearch for development (R4D) projects are designed to enhance the research community's contribution to implementation of the 2030 Agenda of the United Nations. We studied seven R4D projects that specifically addressed Sustainable Development Goal (SDG) 15 (life on land) in 14 contexts across Asia, Africa, and South America. We then analyzed how these projects interacted with other SDGs. Our findings reveal that the positive and negative interactions between project objectives and SDG targets vary significantly across contexts, highlighting the importance of considering local conditions when designing and implementing R4D initiatives.Technical summaryWe analyze how the objectives of research for development (R4D) projects that focus on a particular Sustainable Development Goal (SDG) – SDG 15 (life on land) – interact with the targets of other SDGs. We studied seven R4D projects in 14 contexts across Asia, Africa, and Latin America, comparing expert judgement of interactions between project objectives and SDG targets. Our findings indicate that the success of these projects depends largely on whether they are also working toward SDG targets other than those contained in SDG 15. In particular, working toward targets contained within SDGs on poverty, hunger, water, energy, production and consumption, and global partnerships – was often considered indivisible from the project objectives. Further, while all of the projects focused on SDG 15, our findings suggest that addressing only this goal is not sufficient. A range of other targets that were a priori not the immediate focus of the projects were revealed as ‘crucial’ to the project objectives across contexts. Finally, we list several implications, such as the need for policies to integrate local realities and the need for environmental R4D projects to adopt a holistic scope, particularly in terms of (a) securing social foundations, (b) building enabling institutions, and (c) negotiating competing claims on land.Social media summaryWhat can we learn from land-related research for development projects and their links to the SDGs in concrete contexts?

Background Drawing the epigenome landscape of Alzheimer’s disease (AD) still remains a challenge. To characterize the epigenetic molecular basis of the human hippocampus in AD, we profiled genome-wide DNA methylation levels in hippocampal samples from a cohort of pure AD patients and controls by using the Illumina 450K methylation arrays. Results Up to 118 AD-related differentially methylated positions (DMPs) were identified in the AD hippocampus, and extended mapping of specific regions was obtained by bisulfite cloning sequencing. AD-related DMPs were significantly correlated with phosphorylated tau burden. Functional analysis highlighted that AD-related DMPs were enriched in poised promoters that were not generally maintained in committed neural progenitor cells, as shown by ChiP-qPCR experiments. Interestingly, AD-related DMPs preferentially involved neurodevelopmental and neurogenesis-related genes. Finally, InterPro ontology analysis revealed enrichment in homeobox-containing transcription factors in the set of AD-related DMPs. Conclusions These results suggest that altered DNA methylation in the AD hippocampus occurs at specific regulatory regions crucial for neural differentiation supporting the notion that adult hippocampal neurogenesis may play a role in AD through epigenetic mechanisms. Graphical abstract

Background Advances in the field of genetics of interstitial lung diseases (ILDs) have led to the recent consensus statements made by expert groups. International standards for genetic testing in ILD have not yet been established. We aimed to examine current real-world strategies employed by pulmonologists working with familial ILD. Methods A panel of pulmonologists with expertise in ILD developed an international survey aimed at clinicians working with ILD. The survey consisted of 74 questions divided into eight topics: characteristics of respondents, diagnosis, screening of first-degree relatives, screening tools, genetic testing methods, lung transplantation, ethical concerns, and future needs. Results Overall, 237 pulmonologists from 50 countries participated. A family history of ILD was asked for by 91% of respondents while fewer asked for symptoms related to telomere disorders. Respondents stated that 59% had access to genetic testing, and 30% to a genetic multidisciplinary team (MDT). Many respondents were unaware of specific genetic testing methods. Pathogenic genetic variants were seen as a potential contraindication for lung transplantation in 6–8% of respondents. Genetic screening of relatives was supported by 80% of respondents who indicated insufficient evidence and a lack of formal guidelines for genetics and ILD. Only 16% had a standardized program. Conclusion Most pulmonologists ask for a family history of ILD and recommend genetic testing for ILD and screening in relatives but have limited knowledge of specific tests and access to genetic MDT. Evidence-based guidelines to inform patients, relatives, and physicians are still warranted.

There is considerable variability in how older adults with cancer tolerate and recover from surgery and systemic treatments. A greater understanding of individual trajectories is crucial in guiding personalized treatment decisions. Frailty may explain these inter-individual differences. Despite emerging evidence on the association between perioperative frailty assessment and outcomes after noncardiac surgery, there is limited data in gynecologic oncology. A perioperative cardiovascular risk assessment, recommended by scientific guidelines, is widely adopted in noncardiac surgery, often as the only standardized perioperative risk stratification approach. While based on robust evidence on the association with cardiovascular complications and overall mortality, it might be insufficient to predict other essential surgical, oncologic and patient-important outcomes. The FARGO study is a multi-centre prospective cohort study targeting 280 patients aged 55 or older undergoing surgery, with or without chemotherapy, for a suspected or confirmed gynecologic malignancy. The primary objective is to evaluate the predictive value of the Frailty Phenotype measured preoperatively, compared with the currently used perioperative risk assessment (cardiovascular risk assessment based on the Revised Cardiac Risk Index, age, and occurrence of myocardial injury after non-cardiac surgery) in predicting the composite outcome of all-cause death or new disability at six months after surgery. Secondary objectives include comparing the predictive value of the Frailty Phenotype with that of the Clinical Frailty Scale; evaluating the performance of a preoperative frailty assessments on other postoperative complications, chemotherapy tolerance, and 1-year recurrence-free survival; exploring the added predictive value of a dynamic perioperative frailty assessment repeated 28 days after surgery; assessing the acceptability of frailty assessments by physicians and patients; and establishing a biobank to investigate frailty biomarkers. The findings could have important implications for risk stratification, planning and tailoring surgical and oncologic care for older adults with gynecologic malignancies. Our study emphasizes patient-centered outcomes and stakeholders' perspectives.

Chromatin of male and female gametes undergoes a number of reprogramming events during the transition from germ cell to embryonic developmental programs. Although the rearrangement of DNA methylation patterns occurring in the zygote has been extensively characterized, little is known about the dynamics of DNA modifications during spermatid maturation. Here, we demonstrate that the dynamics of 5-carboxylcytosine (5caC) correlate with active transcription of LINE-1 retroelements during murine spermiogenesis. We show that the open reading frames of active and evolutionary young LINE-1s are 5caC-enriched in round spermatids and 5caC is eliminated from LINE-1s and spermiogenesis-specific genes during spermatid maturation, being simultaneously retained at promoters and introns of developmental genes. Our results reveal an association of 5caC with activity of LINE-1 retrotransposons suggesting a potential direct role for this DNA modification in fine regulation of their transcription.Blythe et al investigate the patterns of oxidized forms of the 5-methylcytosine DNA modification during spermatogenesis. They find that open reading frames of evolutionarily young and transcriptionally active LINE-1 retrotransposons are enriched in 5-carboxylcytosine (5caC) during spermatid maturation, suggesting a link between 5cac and LINE-1 activity.