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Abstract Aims Right ventricular failure after left ventricular assist device (LVAD) implantation is a major concern that remains challenging to predict. We sought to investigate the relationship between preoperative pulmonary artery pulsatility index (PAPi) and mortality after LVAD implantation. Methods and results A retrospective analysis of the ASSIST‐ICD multicentre registry allowed the assessment of PAPi before LVAD according to the formula [(systolic pulmonary artery pressure − diastolic pulmonary artery pressure)/central venous pressure]. The primary endpoint was survival at 3 months, according to the threshold value of PAPi determined by the receiver operating characteristic (ROC) curve. A multivariate analysis including demographic, echographic, haemodynamic, and biological variables was performed to identify predictive factors for 2 year mortality. One hundred seventeen patients were included from 2007 to 2021. The mean age was 58.45 years (±13.16), with 15.4% of women (sex ratio 5.5). A total of 53.4% were implanted as bridge to transplant and 43.1% as destination therapy. Post‐operative right ventricular failure was observed in 57 patients (48.7%), with no significant difference between survivors and non‐survivors at 1 month (odds ratio 1.59, P = 0.30). The median PAPi for the whole study population was 2.83 [interquartile range 1.63–4.69]. The threshold value of PAPi determined by the ROC curve was 2.84. Patients with PAPi ≥ 2.84 had a higher survival rate at 3 months [PAPi

Background Peripartum cardiomyopathy (PPCM) outcomes have been previously linked to demographic and social factors. The social vulnerability index (SVI) is a measure of social vulnerability in the United States. We explored PPCM disparities and the impact of SVI on PPCM mortality. Methods and Results Mortality from 1999 to 2020, SVI, and demographic data were obtained from CDC databases. County‐specific SVI rankings were linked to PPCM age‐adjusted mortality rates (AAMRs), allowing for a comparative analysis of AAMRs across both cumulative populations and subpopulations to identify disparities. All US counties were then stratified into low‐ and high‐SVI groups, facilitating comparison of SVI rankings by estimation of excess‐deaths per 1 000 000 person‐years attributable to greater social vulnerability and rate ratios (RR) through univariable Poisson regression. We identified a total of 1026 deaths related to PPCM between 1999 and 2020. Overall AAMR increased from 0.180 in 1999 to 0.326 in 2020. Black populations (AAMR: 1.081) and Southern US counties (AAMR: 0.444) had the highest AAMRs compared with other racial and US census groups, respectively. Higher SVI accounted for 0.172 excess deaths per 1 000 000 person‐years (RR=1.800). Among Black and White populations, higher SVI also accounted for 0.248 and 0.071 excess deaths per 1 000 000 person‐years, respectively. Similar impacts of greater social vulnerability were observed when comparing the US census regions (Northeast RR=1.609, Midwest RR=1.819, South RR=1.934, West RR=1.776). Conclusions PPCM mortality disparities exist across racial and geographic populations in the United States. A greater burden of social vulnerability is associated with higher PPCM mortality on a national level.

Key Clinical Message The differential diagnoses of popliteal ganglion cysts include Baker's cysts, popliteal artery aneurysms, popliteal tendinitis, popliteal lymphadenopathy, lipomas, and synovial sarcoma.

Abstract Background The impact of chronic kidney disease (CKD) on atrial fibrillation outcomes (AF) is not well understood. Methods We conducted analyses of comorbid AF and CKD related death in the United States from 1999 to 2020 using descriptive epidemiology. Results Age‐adjusted mortality rates (AAMR) per 100,000 increased from 0.39 in 1999 to 1.65 in 2020. Non‐Hispanic populations (1.01) and nonmetropolitan areas (1.08) had higher AAMRs compared to Hispanic (0.62) and metropolitan (0.97) areas. Midwestern (1.11) and Western (1.13) US regions recorded the highest AAMRs. Conclusions These findings highlight the need for interventions to address AF death disparities in patients with CKD.

Key Clinical Message Inguinal swelling should raise suspicion for hip joint osteochondromatosis. Early recognition, accurate diagnosis, and prompt surgical intervention are essential for optimizing patient outcomes.

Abstract Background Multiple methods of quantifying social determinants of health exist, such as the social vulnerability index (SVI). We assess the impact of the SVI on atrial fibrillation (AF)‐related cardiovascular disease mortality. Methods CDC databases were used to obtain mortality and SVI information. Age‐adjusted mortality rates (AAMR) were compared among all US counties, aggregated by SVI quartiles. Results AAMR was not increased in counties within the highest SVI quartile, consistent across gender and geographic subgroups. Conclusions Increased SVI is a poor marker to predict mortality outcomes associated with AF.

Abstract Background The majority of pancreatic ductal adenocarcinoma (PDAC) patients experience disease progression while on treatment with gemcitabine and nanoparticle albumin‐bound (nab)‐paclitaxel (GemPac) necessitating the need for a more effective treatment strategy for this refractory disease. Previously, we have demonstrated that nuclear exporter protein exportin 1 (XPO1) is a valid therapeutic target in PDAC, and the selective inhibitor of nuclear export selinexor (Sel) synergistically enhances the efficacy of GemPac in pancreatic cancer cells, spheroids and patient‐derived tumours, and had promising activity in a phase I study. Methods Here, we investigated the impact of selinexor–gemcitabine–nab‐paclitaxel (Sel‐GemPac) combination on LSL‐KrasG12D/+; LSL‐Trp53R172H/+; Pdx1‐Cre (KPC) mouse model utilising digital spatial profiling (DSP) and single nuclear RNA sequencing (snRNAseq). Results Sel‐GemPac synergistically inhibited the growth of the KPC tumour‐derived cell line. The Sel‐GemPac combination reduced the 2D colony formation and 3D spheroid formation. In the KPC mouse model, at a sub‐maximum tolerated dose (sub‐MTD) , Sel‐GemPac enhanced the survival of treated mice compared to controls (p

Abstract Basaltic lavas from Harrat Uwayrid, Saudi Arabia, record the evolving magmatic and tectonic context of the Arabian Peninsula from at least the mid‐Miocene to the present day. New 40Ar/39Ar ages spanning from the mid to late Miocene reveal that mid‐Miocene mafic volcanism formed a large, subalkaline volcanic plateau parallel to Red Sea rifts. Subsequent volumetrically subordinate late Miocene‐Quaternary alkaline volcanism erupted monogenetic cinder cones roughly orthogonal to the earlier volcanic field. The source region for all samples was affected by both fluid and silicate metasomatism; inferred mantle mineral assemblages include amphibole for mid‐Miocene lavas and phlogopite for late Miocene‐Quaternary samples. Calculated melting depths become shallower with time across the Miocene volcanic episode (∼20–15 Ma) but become deeper in the late Miocene to Quaternary (∼10–0 Ma), indicating melting pressures and temperatures significantly higher than those recorded in Miocene lavas despite progressive lithospheric thinning. We offer a two‐stage model for the formation of Harrat Uwayrid: (a) Early‐ and mid‐Miocene rifting associated with the Red Sea opening facilitated adiabatic melting of uppermost mantle lithosphere to form the early volcanic plateau and (b) Plate motion changes in the mid‐ and late‐Miocene initiated the Dead Sea Fault and destabilized a dense pyroxenitic lower lithosphere leading to foundering or lithospheric drip beneath Harrat Uwayrid that allowed deep lithospheric melting and formed the young volatile‐rich eruptives.

Abstract Transmembrane protein 14A (TMEM14A) is a relatively unknown protein that is now identified to be required for maintaining the integrity of the glomerular filtration barrier. It is an integral transmembrane protein of 99 amino acids with three transmembrane domains. TMEM14A has been implied to suppress Bax‐mediated apoptosis in other studies. Other than that, little is currently known of its function. Here, we show that its expression is diminished before onset of proteinuria in a spontaneously proteinuric rat model. Knocking down tmem14a mRNA translation results in proteinuria in zebrafish embryos without affecting tubular reabsorption. Also, it is primarily expressed by podocytes. Lastly, an increase in glomerular TMEM14A expression is exhibited in various proteinuric renal diseases. Overall, these results suggest that TMEM14A is a novel factor in the protective mechanisms of the nephron to maintain glomerular filtration barrier integrity.

Key Clinical Message Currently, there is no consensus on the optimal management of nonmetastatic Ewing's sarcoma of the mobile spine. However, associated to chemotherapy, aggressive surgery with en bloc wide resection seems to improve local control and survival. Abstract Primary Ewing's sarcoma (EWS) of non‐sacral spine is extremely rare, especially in middle‐age. Therapeutic strategy aims: to large tumor resection, to provide spine stability and to avoid recurrence through chemo and radiotherapy. We report a case of thoracic spine EWS in an adult treated by combined approach en bloc vertebrectomy.

Key Clinical Message Primary hydatid cyst of the thigh is a rare condition requiring prompt recognition and accurate diagnosis for timely management and prevention of complications. Abstract Muscular hydatid cysts are rare, with a frequency ranging from 1% to 5% even in endemic areas. The clinical presentation of muscular hydatidosis is typically subtle and lacks specific features, frequently resulting in delayed diagnosis. Herein, the authors describe a case of a primary hydatid cyst located in the thigh.

Abstract Background Driven by increased prevalence of type 2 diabetes and ageing populations, wounds affect millions of people each year, but monitoring and treatment remain limited. Glucocorticoid (stress hormones) activation by the enzyme 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) also impairs healing. We recently reported that 11β‐HSD1 inhibition with oral AZD4017 improves acute wound healing by manual 2D optical coherence tomography (OCT), although this method is subjective and labour‐intensive. Objectives Here, we aimed to develop an automated method of 3D OCT for rapid identification and quantification of multiple wound morphologies. Methods We analysed 204 3D OCT scans of 3 mm punch biopsies representing 24 480 2D wound image frames. A u‐net method was used for image segmentation into 4 key wound morphologies: early granulation tissue, late granulation tissue, neo‐epidermis, and blood clot. U‐net training was conducted with 0.2% of available frames, with a mini‐batch accuracy of 86%. The trained model was applied to compare segment area (per frame) and volume (per scan) at days 2 and 7 post‐wounding and in AZD4017 compared to placebo. Results Automated OCT distinguished wound tissue morphologies, quantifying their volumetric transition during healing, and correlating with corresponding manual measurements. Further, AZD4017 improved epidermal re‐epithelialisation (by manual OCT) with a corresponding trend towards increased neo‐epidermis volume (by automated OCT). Conclusion Machine learning and OCT can quantify wound healing for automated, non‐invasive monitoring in real‐time. This sensitive and reproducible new approach offers a step‐change in wound healing research, paving the way for further development in chronic wounds.

Abstract There is growing interest in utilizing pharmacogenetic (PGx) testing to guide antidepressant use, but there is lack of clarity on how to implement testing into clinical practice. We administered two surveys at 17 sites that had implemented or were in the process of implementing PGx testing for antidepressants. Survey 1 collected data on the process and logistics of testing. Survey 2 asked sites to rank the importance of Consolidated Framework for Implementation Research (CFIR) constructs using best‐worst scaling choice experiments. Of the 17 sites, 13 had implemented testing and four were in the planning stage. Thirteen offered testing in the outpatient setting, and nine in both outpatient/inpatient settings. PGx tests were mainly ordered by psychiatry (92%) and primary care (69%) providers. CYP2C19 and CYP2D6 were the most commonly tested genes. The justification for antidepressants selected for PGx guidance was based on Clinical Pharmacogenetics Implementation Consortium guidelines (94%) and US Food and Drug Administration (FDA; 75.6%) guidance. Both institutional (53%) and commercial laboratories (53%) were used for testing. Sites varied on the methods for returning results to providers and patients. Sites were consistent in ranking CFIR constructs and identified patient needs/resources, leadership engagement, intervention knowledge/beliefs, evidence strength and quality, and the identification of champions as most important for implementation. Sites deployed similar implementation strategies and measured similar outcomes. The process of implementing PGx testing to guide antidepressant therapy varied across sites, but key drivers for successful implementation were similar and may help guide other institutions interested in providing PGx‐guided pharmacotherapy for antidepressant management.

Abstract Internal hernias represent only 0.2%–0.9% of all causes of bowel obstruction. A 59‐year‐old patient presented urgently with small bowel obstruction. Laparotomy revealed a left paraduodenal hernia with most of the small bowel herniating through a space between the inferior mesenteric vein and duodenojejunal junction.

Abstract Aims Despite regularly updated guidelines, there is still a delay in referral of advanced heart failure patients to mechanical circulatory support and transplant centres. We aimed to analyse characteristics and outcome of non‐inotrope‐dependent patients implanted with a left ventricular assist device (LVAD). Methods and results The ASSIST‐ICD registry collected LVAD data in 19 centres in France between February 2006 and December 2016. We used data of patients in Interagency Registry for Mechanically Assisted Circulatory Support Classes 4–7. The primary endpoint was survival analysis. Predictors of mortality were searched with multivariable analyses. A total of 303 patients (mean age 61.0 ± 9.9 years, male sex 86.8%) were included in the present analysis. Ischaemic cardiomyopathy was the leading heart failure aetiology (64%), and bridge to transplantation was the main implantation strategy (56.1%). The overall likelihood of being alive while on LVAD support or having a transplant at 1, 2, 3, and 5 years was 66%, 61.7%, 58.7%, and 55.1%, respectively. Age [hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.00–1.05; P = 0.02], a concomitant procedure (HR 2.32, 95% CI 1.52–3.53; P

Abstract Management of bone metastases from renal cell carcinoma (RCC) has significantly changed after the era of targeted therapy that improved the overall survival (OS). Surgical decision‐making remains a subject of controversy. We report a case of pelvic bone metastasis from RCC, 2 months after nephrectomy and surgery of a revealing clavicular metastasis.

Thromboinflammation has become a topic of key interest in cardiovascular disease and the prevention of diabetes complications because of the interplay between thrombosis and inflammation in diabetes. Specifically, the significant risk of vascular thrombotic disease in diabetes highlights the need for new and better therapeutic targets to help manage and prevent vascular thrombo‐occlusive disease in this condition. Similarly, the prominent role of inflammation in diabetes has sparked interest in anti‐inflammatory agents to better prevent and control vascular disease. Investigations on the effects of anticoagulation and antiplatelet interventions in patients with diabetes and cardiovascular disease show a potential role for these agents in decreasing morbidity and mortality. Neutrophils and platelets are key players in inflammation and wound‐healing response, respectively. The interaction between neutrophils and platelets is thought to be an important driver of thromboinflammation. Therefore, this review describes the mechanisms involved in platelet–neutrophil interactions that contribute to the development or exacerbation of thromboinflammation in the context of diabetes and its associated comorbidities. The effects observed by the antithrombotic/antidiabetic treatments and physical activity/dietary interventions on attenuating thromboinflammation are discussed. These data suggest that mechanisms involved in platelet–neutrophil interaction, platelet activation/aggregation, and the recruitment of neutrophils have a promising potential to become therapeutic targets to decrease thromboinflammation in patients with diabetes.

Abstract Importance Atrial fibrillation is the most clinically significant arrhythmia in humans when viewed both from a global and also a national perspective. In the United States, approximately 2.7‐6.1 million people are estimated to have atrial fibrillation. With the aging of the population, this prevalence is on an increasing trend and remains an obstacle to cardiovascular health despite significant advancements specific to cardiovascular disease management. Observation In this specific group of patients, healthcare utilization is a concern from the public health perspective. Unfortunately, misconceptions dominate clinical decision making; for instance, the avoidance of safe and effective anticoagulation strategies in patients at the highest risk for embolic strokes continues to be widespread in clinical practice and is often based on a skewed assessment of risk versus benefit. Also, when there are contraindications to standard interventions for atrial fibrillation, a clear and nuanced understanding of second‐ and third‐line interventions with proven benefit is often lacking. Conclusions and Relevance An individualized approach should be followed by physicians when managing atrial fibrillation in the elderly patient, taking into consideration the risk of complications, particularly the embolic stroke and the availability of treatment options for stroke prevention whether through pharmacological anticoagulation or left atrial appendage occluding devices. The following review sets out to clarify these issues.

Abstract The right ventricular assessment is crucial to heart disease diagnosis. Unfortunately, its segmentation is quite challenging due to its intricate shape, ill‐defined thin edges, large variability among patients, and pathologies. Besides, it is a very laborious and time‐consuming task to be done manually. Therefore, automated segmentation techniques are very suitable to reduce the strain on the expert. Here, it is attempted to review the taxonomy of the current RV segmentation approaches adopted to handle the afore‐mentioned issues. Enhanced by our expert's interpretation, the results of over forty research papers were evaluated based on several metrics such as the dice metric and the Hausdorff distance. Synthetic tables and charts were also used to discuss the reviewed approaches. The following study shows that none of the existing methods has proved accurate enough to meet all the RV challenging issues. Many misestimated results were reported for several cases. Eventually, global guidance is outlined, which supports combining different methods to enhance the expected results during the MRI short‐axis slice processing.

Background The value of coronary artery calcium (CAC) in the allocation of PCSK9i (proprotein convertase subtilisin/kexin type 9 inhibitors) among individuals without clinically evident atherosclerotic cardiovascular disease (ASCVD) is unknown for indications that do not require confirmed familial hypercholesterolemia. We aimed to assess the ability of CAC to stratify ASCVD risk under 3 non–familial hypercholesterolemia PCSK9i allocation paradigms. Methods and Results We included participants without clinically evident ASCVD from MESA (Multi‐Ethnic Study of Atherosclerosis), CARDIA (Coronary Artery Risk Development in Young Adults) study, DHS (Dallas Heart Study), and HNR (Heinz Nixdorf Recall) study. Three PCSK9i eligibility scenarios were defined: a broad scenario informed only by high low‐density lipoprotein cholesterol levels (N=567), a restrictive one combining higher low‐density lipoprotein cholesterol levels and presence of ≥2 additional risk factors (N=127), and a high‐risk scenario where individuals with subclinical organ damage or high estimated risk would be treated to achieve low‐density lipoprotein cholesterol

Abstract Fire regimes in North American forests are diverse and modern fire records are often too short to capture important patterns, trends, feedbacks, and drivers of variability. Tree‐ring fire scars provide valuable perspectives on fire regimes, including centuries‐long records of fire year, season, frequency, severity, and size. Here, we introduce the newly compiled North American tree‐ring fire‐scar network (NAFSN), which contains 2562 sites, >37,000 fire‐scarred trees, and covers large parts of North America. We investigate the NAFSN in terms of geography, sample depth, vegetation, topography, climate, and human land use. Fire scars are found in most ecoregions, from boreal forests in northern Alaska and Canada to subtropical forests in southern Florida and Mexico. The network includes 91 tree species, but is dominated by gymnosperms in the genus Pinus. Fire scars are found from sea level to >4000‐m elevation and across a range of topographic settings that vary by ecoregion. Multiple regions are densely sampled (e.g., >1000 fire‐scarred trees), enabling new spatial analyses such as reconstructions of area burned. To demonstrate the potential of the network, we compared the climate space of the NAFSN to those of modern fires and forests; the NAFSN spans a climate space largely representative of the forested areas in North America, with notable gaps in warmer tropical climates. Modern fires are burning in similar climate spaces as historical fires, but disproportionately in warmer regions compared to the historical record, possibly related to under‐sampling of warm subtropical forests or supporting observations of changing fire regimes. The historical influence of Indigenous and non‐Indigenous human land use on fire regimes varies in space and time. A 20th century fire deficit associated with human activities is evident in many regions, yet fire regimes characterized by frequent surface fires are still active in some areas (e.g., Mexico and the southeastern United States). These analyses provide a foundation and framework for future studies using the hundreds of thousands of annually‐ to sub‐annually‐resolved tree‐ring records of fire spanning centuries, which will further advance our understanding of the interactions among fire, climate, topography, vegetation, and humans across North America.

Abstract Nasopharyngeal teratomas are rare and represent only 2% of all teratomas. They can lead to an embryopathogenic mechanical obstacle responsible for a cleft palate with few reported cases of this association in the literature. We report the case of a 14‐month‐old girl with this atypical association.

Abstract Background Autophagy is a conserved recycling process in cells. However, the effects of autophagy on the remission and treatment response of acute myeloid leukemia (AML) patients have not been clarified. Methods The expression of MAP1LC3B, ATG5, ATG10, RB1CC1, and AMBRA1 genes was assessed in 32 newly diagnosed AML patients, 18 complete remission (CR) patients, and seven relapsed patients, as well as 15 controls, by real‐time polymerase chain reaction (PCR). Results The expression of all five genes was significantly higher in the newly diagnosed AML patients as compared to the controls (p

Abstract Case presentation This case report concerns a 49‐year‐old woman who developed cholestasis (build‐up of bile in the liver) two months and a half after initiating norethisterone, progestin‐only pills, which resolved after the withdrawal of these pills.

Abstract Background and Aims Quality of care has transformed to become an essential element of healthcare service delivery, which caused decision makers in Health Care Organisations (HCOs) to seek methods to evaluate the level of care provided. The field of accreditation is under massive development, especially in healthcare organizations. Joint Commission International (JCI) accreditation is one of the accreditation bodies that require a lot of documentation and quality improvement to guarantee proper standard application. The process of accreditation is known to be demanding and requires staff involvement to guarantee successful implementation. Methods This study focuses on the impact of JCI standards implementation on staff productivity and motivation in a 350‐bed hospital. An interpretive approach was used to collect empirical data by interpreting the population's behavior, which is represented in this study by the questionnaire. The study is considered an emergent study that identified, explained, illustrated, and developed a model of staff motivation. In this type of study, the process of inquiry, supporting arguments, and questions of interest is developed after the launching of the study and during the process of data collection. Thus, the researcher relied on the social constructive paradigm, whereby the grounded theory (GT) is used to build the research model of staff motivation during the process of accreditation. Results By studying the Turn Around Time (TAT) performance indicator, the study showed that TAT of tests decreased by 3% after JCI standards implementation, which was reflected at two different laboratory sections. The trainings conducted throughout the process of standards implementation also resulted in enhancing the quality of samples, which was demonstrated by the decrease in the percentage of rejected samples. Conclusion Staff productivity increases when JCI standards are implemented. However, staff motivation is dependent on their involvement with management decisions and the smooth transition through change management, which ensures staff retention and therefore increase productivity.

Obesity is a risk factor for triple‐negative breast cancer (TNBC) incidence and poor outcomes, but the underlying molecular biology remains unknown. We previously identified in TNBC cell cultures that expression of epigenetic reader methyl‐CpG‐binding domain protein 2 (MBD2), specifically the alternative mRNA splicing variant MBD variant 2 (MBD2_v2), is dependent on reactive oxygen species (ROS) and is crucial for maintenance and expansion of cancer stem cell‐like cells (CSCs). Because obesity is coupled with inflammation and ROS, we hypothesized that obesity can fuel an increase in MBD2_v2 expression to promote the tumor‐initiating CSC phenotype in TNBC cells in vivo. Analysis of TNBC patient datasets revealed associations between high tumor MBD2_v2 expression and high relapse rates and high body mass index (BMI). Stable gene knockdown/overexpression methods were applied to TNBC cell lines to elucidate that MBD2_v2 expression is governed by ROS‐dependent expression of serine‐ and arginine‐rich splicing factor 2 (SRSF2). We employed a diet‐induced obesity (DIO) mouse model that mimics human obesity to investigate whether obesity causes increased MBD2_v2 expression and increased tumor initiation capacity in inoculated TNBC cell lines. MBD2_v2 and SRSF2 levels were increased in TNBC cell line‐derived tumors that formed more frequently in DIO mice relative to tumors in lean control mice. Stable MBD2_v2 overexpression increased the CSC fraction in culture and increased TNBC cell line tumor initiation capacity in vivo. SRSF2 knockdown resulted in decreased MBD2_v2 expression, decreased CSCs in TNBC cell cultures, and hindered tumor formation in vivo. This report describes evidence to support the conclusion that MBD2_v2 expression is induced by obesity and drives TNBC cell tumorigenicity, and thus provides molecular insights into support of the epidemiological evidence that obesity is a risk factor for TNBC. The majority of TNBC patients are obese and rising obesity rates threaten to further increase the burden of obesity‐linked cancers, which reinforces the relevance of this report.