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Abstract Aims We aimed to analyse the characteristics and in‐hospital outcomes of patients hospitalized for heart failure (HF) with co‐morbid systemic sclerosis (SSc) and compare them to those without SSc, using data from the National Inpatient Sample from years 2016 to 2019. Methods and results International Classification of Diseases, Tenth Revision diagnosis codes were used to identify hospitalized patients with a primary diagnosis of HF and secondary diagnoses of SSc from the National Inpatient Sample database from 2016 to 2019. Patients were divided into two groups: those with and without a secondary diagnosis of SSc. Baseline characteristics including demographics and co‐morbidities, outcomes of mortality, length of stay (LOS), and costs were compared between the two groups. Multivariable logistic regression analysis was performed to adjust for confounders and assess the impact of SSc on in‐hospital mortality, cost, and LOS. A total of 4 709 724 hospitalizations for HF were identified, with 8150 (0.17%) having a secondary diagnosis of SSc. These patients were predominantly female (82.3% vs. 47.8%; P = 0.01), younger (mean age of 67.4 vs. 71.4; P

Ivo Abraham,1 Mickael Hiligsmann,2 Kenneth KC Lee,3 Leslie Citrome,4 Giorgio Lorenzo Colombo,5 Mike Gregg6 1University of Arizona, Tucson, AZ, USA; 2Maastricht University, Maastricht, the Netherlands; 3Taylor’s University, Selangor, Malaysia; 4New York Medical College, Valhalla, New York, NY, USA; 5University of Pavia, Pavia, Italy; 6Taylor & Francis, London, SE1 8BF, UKCorrespondence: Mike Gregg, Email mike.gregg@tandf.co.uk

Abstract Aims Pulmonary artery pressure (PAP)‐guided therapy in patients with heart failure (HF) using the CardioMEMS (CMM) device, an implantable PAP sensor, has been shown to reduce HF hospitalizations in previous studies. We sought to evaluate the clinical benefit of the CMM device in regard to 30, 90, and 180 day readmission rates in real‐world usage. Methods and results We queried the Nationwide Readmissions Database (NRD) to identify patients who underwent CMM implantation (International Classification of Diseases 9 and 10 codes) between the years 2014 and 2019 and studied their HF readmissions. Moreover, we compared CMM patients and their readmissions with a matched cohort of patients with HF but without CMM. Multivariable Cox regression analysis was performed to adjust for other predictors of readmissions. Prior to matching, we identified 5 326 530 weighted HF patients without CMM and 1842 patients with CMM. After propensity score matching for several patients and hospital‐related characteristics, the cohort consisted of 1839 patients with CMM and 1924 with HF without CMM. Before matching, CMM patients were younger (67.0 ± 13.5 years vs. 72.3 ± 14.1 years, P

Abstract Background The frequency of surgical site infection (SSI) following orthopaedic implant placement in horses has been reported but not compared with respect to specific antibiotic protocols administered. Objectives To determine factors associated with SSI in horses undergoing proximal interphalangeal joint (PIPJ) arthrodesis including perioperative antibiotic protocols. Methods Records were evaluated (2010–2019), and horses undergoing PIPJ arthrodesis were identified. Patient signalment, supervising surgeon, reason for surgery, limb, implants placed, anaesthetic time, duration casting/coaptation postoperatively, antibiotic regimen and incidence/onset SSI were recorded. Bayesian and frequentist logistic regressions were used to estimate the contribution of covariates to infection occurrence. Results Fifty‐four PIPJ arthrodeses were performed. SSI occurred in 2/54 (3.7%) on day 15,30. Arthrodesis was performed most commonly for osteoarthritis (33/54, 61.1%), fracture (11/54, 20.4%), and subluxation (5/54, 9.3%). Perioperative systemic antibiotics were administered 1–3 days (15/54, 27.8%) or > 3 days (39/54, 72.2%). Antibiotic protocols included cefazolin/gentamicin (20/54, 37%), cefazolin/gentamicin/doxycycline (14/54, 25.9%) and potassium penicillin/gentamicin (10/54, 18.5%). Regional limb perfusion was performed preoperatively 31/54 (57.4%) and postoperatively 7/54 (13%). Survival to dismissal was 98.1% (53/54 horses) with one horse euthanized due to support limb laminitis. No association was identified between antibiotic selection or duration (1–3 vs. > 3 days), pre‐operative regional antibiotic perfusion, intraoperative antibiotic lavage or anaesthetic time ( 3 h) and SSI; however, modelling was complicated by quasi‐complete or complete separation of the data. Bayesian analysis (but not frequentist analysis) indicated an association between post‐operative regional antibiotic perfusion and SSI. Limitations include the retrospective nature of data collection and the low rate of infection overall. Conclusions The prevalence of SSI in this population was lower than that in previous reports of equine orthopaedic internal fixation. There was no difference in SSI rate in cases administered systemic antibiotics for 1–3 days or >3 days, or for those horses that did or did not receive preoperative regional antibiotic perfusion.

Background. Scarcity of donor hearts continues to be a challenge for heart transplantation (HT). The recently Food and Drug Administration–approved Organ Care System (OCS; Heart, TransMedics) for ex vivo organ perfusion enables extension of ex situ intervals and thus may expand the donor pool. Because postapproval real-world outcomes of OCS in HT are lacking, we report our initial experience. Methods. We retrospectively reviewed consecutive patients who received HT at our institution in the post–Food and Drug Administration approval period from May 1 to October 15, 2022. Patients were divided into 2 groups: OCS versus conventional technique. Baseline characteristics and outcomes were compared. Results. A total of 21 patients received HT during this period, 8 using OCS and 13 conventional techniques. All hearts were from donation after brain death donors. The indication for OCS was an expected ischemic time of >4 h. Baseline characteristics in the 2 groups were comparable. The mean distance traveled for heart recovery was significantly higher in the OCS group (OCS, 845 ± 337, versus conventional, 186 ± 188 mi; P

Welfare state research over the past five decades has largely focused on two broad social policy pillars: (1) arrays of income programmes, such as social assistance, unemployment insurance, family allowances and pensions, and (2) a range of social services, including childcare, healthcare, social housing and education. However, an important cluster of policy measures, constituting a third policy pillar, has been largely neglected in the cross-national welfare state research to date, protective legislation. It comprises the networks of protective and regulatory laws and constitutional rights emplaced to secure and promote our welfare. Central to all social policy areas, these measures, including rent control policies, workplace health and safety laws, legislation preventing discrimination against people with disabilities and child corporal punishment bans, are distinct from laws that determine access to income programmes and social services or set out the terms of their provision. Rather, they constitute a standalone third category of policy measures, are key components of all welfare states and, depending upon how they are actualised, can be just as central to our well-being and the promotion of our welfare. They can also have compounding or synergistic interactions with policies in the other two policy pillars. [ABSTRACT FROM AUTHOR]

Abstract Background Obesity is an established risk factor for cardiometabolic disease and heart failure (HF). Nevertheless, the relationship between obesity and HF mortality remains controversial. Results The goal of this study was to describe the prevalence of obesity in patients hospitalized for HF in Egypt and investigate the relationship of obesity to cardiometabolic risk factors, HF phenotype and mortality. Between 2011 and 2014, 1661 patients hospitalized for HF across Egypt were enrolled as part of the European Society of Cardiology HF Long-term Registry. Obese patients, defined by a BMI ≥ 30 kg/m2, were compared to non-obese patients. Factors associated with mortality on univariate analysis were entered into a logistic regression model to identify whether obesity was an independent predictor of mortality during hospitalization and at one-year follow-up. The prevalence of obesity was 46.5% and was higher in females compared to males. Obese as compared to non-obese patients had a higher prevalence of diabetes mellitus (47.0% vs 40.2%, p = 0.031), hypertension (51.3% vs 33.0%, p

IntroductionMultiple biological therapies for orthopedic injuries are marketed to veterinarians, despite a lack of rigorous comparative biological activity data to guide informed decisions in selecting a most effective compound. Therefore, the goal of this study was to use relevant bioassay systems to directly compare the anti-inflammatory and immunomodulatory activity of three commonly used orthobiological therapies (OTs): mesenchymal stromal cells (MSC), autologous conditioned serum (ACS), and platelet rich plasma (PRP).MethodsEquine monocyte-derived macrophages were used as the readout system to compare therapies, including cytokine production and transcriptomic responses. Macrophages were stimulated with IL-1ß and treated 24 h with OTs, washed and cultured an additional 24 h to generate supernatants. Secreted cytokines were measured by multiplex immunoassay and ELISA. To assess global transcriptomic responses to treatments, RNA was extracted from macrophages and subjected to full RNA sequencing, using an Illumina-based platform. Data analysis included comparison of differentially expressed genes and pathway analysis in treated vs. untreated macrophages.ResultsAll treatments reduced production of IL-1ß by macrophages. Secretion of IL-10 was highest in MSC-CM treated macrophages, while PRP lysate and ACS resulted in greater downregulation of IL-6 and IP-10. Transcriptomic analysis revealed that ACS triggered multiple inflammatory response pathways in macrophages based on GSEA, while MSC generated significant downregulation of inflammatory pathways, and PRP lysate induced a mixed immune response profile. Key downregulated genes in MSC-treated cultures included type 1 and type 2 interferon response, TNF-α and IL-6. PRP lysate cultures demonstrated downregulation of inflammation-related genes IL-1RA, SLAMF9, ENSECAG00000022247 but concurrent upregulation of TNF-α, IL-2 signaling, and Myc targets. ACS induced upregulation of inflammatory IL-2 signaling, TNFα and KRAS signaling and hypoxia, but downregulation of MTOR signaling and type 1 interferon signaling.DiscussionThese findings, representing the first comprehensive look at immune response pathways for popular equine OTs, reveal distinct differences between therapies. These studies address a critical gap in our understanding of the relative immunomodulatory properties of regenerative therapies commonly used in equine practice to treat musculoskeletal disease and will serve as a platform from which further in vivo comparisons may build.

Pleural effusions appearing within the first 30 postoperative days following coronary artery bypass grafting (CABG) are classified as early and believed to be directly related to the surgery. The characteristics of such effusions are well-described. Orthotopic heart transplantation is also known to be complicated by pleural effusions; however, their characteristics have not been systematically reported. We assessed the features of early postoperative pleural effusions after heart transplantation and compared them to those of early effusions following CABG.

The halenaquinol family of naphthoquinol natural products includes a few closely related polycyclic compounds that feature an activated, electrophilic furan ring. This motif is likely responsible for the rich biological activity attributed to these secondary metabolites. Their interesting structures-related via their electrophilic furan to the biologically important furanosteroids-and their activities prompted significant efforts by organic chemists that resulted in many strategically compelling laboratory syntheses of these targets. These different strategies are compared and contrasted in this Microreview, and the authors' recent work on the structurally different but biogenetically related natural product exiguaquinol is put into the context of the previous studies on halenaquinol-type targets.

A concise and stereoselective synthesis of exiguaquinol dessulfate is described. Sequential application of a Diels-Alder cycloaddition, a desymmetrizing aldol addition, and a reductive Heck cyclization established most of the architecture of exiguaquinol, and a carefully choreographed introduction of the polar substituents afforded the title compound; unfortunately, naphthoquinol sulfation could not be achieved to deliver exiguaquinol. Our hypothesis regarding the configurational preference of the N-acyl hemiaminal, which was based upon an analysis of internal hydrogen-bonding interactions with polar functional groups, was proven correct. A late-stage intermediate did not demonstrate bactericidal activity against H. pylori cultures.

Abstract Background Prophylactic perioperative antimicrobial protocols in equine synovial endoscopy have been described but not compared with respect to post‐operative outcomes and complications. Increasing antimicrobial resistance in equine practice and interest in promoting judicious use of antimicrobials has prompted reevaluation of drug selection and dosing strategies. Objectives To determine the frequency of and compare post‐operative complications following elective synovial endoscopy between horses receiving different perioperative antimicrobial protocols. Methods Records from the Colorado State University Veterinary Teaching Hospital were evaluated (2014–2018) and equine patients undergoing elective synovial endoscopy were identified. Patients undergoing endoscopy for sepsis or internal fixation were excluded. Patient signalment, clinician, joint and limb involved, perioperative antimicrobial regimen, number endoscopic portals and closure technique, and post‐operative complications including incidence of joint infection were recorded. Generalized linear models were used to estimate the odds of post‐operative complications. Results Elective synovial endoscopies of 516 horses in 537 procedures evaluating 761 synovial structures were performed. No horses developed post‐operative septic synovitis. Administration of post‐operative antimicrobials, type used and patient sex were all significantly associated with increased risk of complications, which were predominantly gastrointestinal‐related. Complication rates in horses receiving a single preoperative dose of cefazolin were lower than in horses receiving potassium penicillin, gentamicin or multiple doses. Complication rates were lower in females compared to castrated or intact males. Other factors evaluated (breed, age, surgeon, anaesthesia duration or hospitalization, joint/limb operated, number endoscopic portals) were not associated with increased risk of complications post‐operatively in this case population. Conclusions Prophylactic perioperative antimicrobial protocols in equine practice deserve periodic reconsideration due to increased antimicrobial resistance. Prolonged antimicrobial usage beyond the time of surgery was unnecessary to prevent septic synovitis following synovial endoscopy in this case population and was furthermore associated with an increased risk of gastrointestinal complications.

Background: The axillary artery (AX) access for intra‐aortic balloon pump (IABP) as a bridge to heart transplant (HT) allows mobility while awaiting a suitable donor. As end‐stage heart failure patients often have an implantable cardioverter defibrillator (ICD) on the left side, the left AX approach may be avoided due to the perception of difficult access and proximity of two devices. We aimed to evaluate the outcomes of patients bridged to HT with a left‐sided AX IABP with or without ipsilateral ICDs. Methods: We retrospectively reviewed HT candidates at our institution supported by left‐sided axillary IABP from November 2019 to February 2024, dividing them into two groups based on the presence (Group ICD, n = 48) or absence (Group No‐ICD, N = 19) of an ipsilateral left‐sided ICD. The exposure time was defined as the time from skin incision to the beginning of anastomoses of a Dacron graft. Results: Technical success was achieved in 100% of the cohort, with median exposure times for AX access similar between groups (ICD, 12 [7.8, 18.2] vs. No ICD, 11 [7, 19] min; p = 0.75). The rate of procedural adverse events, such as significant access site bleeding and ipsilateral limb ischemia, did not significantly differ between both groups. Device malfunction rates were comparable (ICD, 29.2% vs. No ICD, 15.8%; p = 0.35). Posttransplant, in‐hospital mortality, severe primary graft dysfunction, and stroke rates were comparable in both groups. Conclusion: The presence of an ipsilateral left‐sided ICD does not adversely impact the procedural efficacy, complication rates, or posttransplant outcomes of left‐sided AX IABP insertion in HT candidates. [ABSTRACT FROM AUTHOR]

Abstract The loss of ten‐eleven translocation (TET2) methylcytosine dioxygenase expression contributes to the pathobiology of pulmonary arterial hypertension (PAH). However, whether the expression and activity of other TETs and DNA methyltransferases (DNMTs) are altered in PAH remains enigmatic. Therefore, our objective was to determine the expression of DNMT (1, 3a, and 3b) and TET (1, 2, and 3) and their total activity. We assessed the expression of DNMT and TET enzymes in the leukocytes and their activity in extracellular vesicles (EVs). Expression of DNMT (1, 3a, and 3b), TET (2 and 3) in leukocytes, and total activity in EVs, from PAH patients was higher than in healthy controls. Additionally, we noticed there were difference in expression of these epigenetic enzyme based on ethnicity and found higher DNMT1 and lower TET2/TET3 expression in Caucasian than Hispanic/African American (combine) patients. Since loss‐of‐function mutation(s) and down‐regulation of TET enzymes are associated with hematological malignancies and cytokine production, we determined the expression of genes that encode cytokines in samples of Caucasian and Hispanic/African American patients. Expression of IL6, CSF2, and CCL5 genes were higher in the leukocytes of Caucasian than Hispanic/African American patients, and CSF2 and CCL5 negatively correlated with the decreased expression of TET3. Interestingly, the expression of gene encoding CD34, a marker of myeloid and lymphoid precursor cells, and CD163, a monocyte/macrophage protein, was higher in the leukocytes of Caucasian than Hispanic/African American patients. Furthermore, Hispanic/African American patients having higher TET2/TET3 expression had higher pulmonary capillary wedge pressure. In conclusion, our results revealed higher DNMT1 and lower TET2/TET3 in Caucasian than Hispanic/African American patients together potentially augmented genes encoding inflammation causing cytokines, and CD34+‐derived immunogenic cells, and the severity of PAH.