Resident cardiac macrophages mediate adaptive myocardial remodeling.

Cardiac macrophages represent a heterogeneous cell population with distinct origins, dynamics, and functions. Recent studies have revealed that C-C Chemokine Receptor 2 positive (CCR2+) macrophages derived from infiltrating monocytes regulate myocardial inflammation and heart failure pathogenesis. Comparatively little is known about the functions of tissue resident (CCR2-) macrophages. Herein, we identified an essential role for CCR2- macrophages in the chronically failing heart. Depletion of CCR2- macrophages in mice with dilated cardiomyopathy accelerated mortality and impaired ventricular remodeling and coronary angiogenesis, adaptive changes necessary to maintain cardiac output in the setting of reduced cardiac contractility. Mechanistically, CCR2- macrophages interacted with neighboring cardiomyocytes via focal adhesion complexes and were activated in response to mechanical stretch through a transient receptor potential vanilloid 4 (TRPV4)-dependent pathway that controlled growth factor expression. These findings establish a role for tissue-resident macrophages in adaptive cardiac remodeling and implicate mechanical sensing in cardiac macrophage activation.

The Transcription Factor RXRα in CD11c+ APCs Regulates Intestinal Immune Homeostasis and Inflammation.

APCs such as dendritic cells and macrophages play a pivotal role in mediating immune tolerance and restoring intestinal immune homeostasis by limiting inflammatory responses against commensal bacteria. However, cell-intrinsic molecular regulators critical for programming intestinal APCs to a regulatory state rather than an inflammatory state are unknown. In this study, we report that the transcription factor retinoid X receptor α (RXRα) signaling in CD11c+ APCs is essential for suppressing intestinal inflammation by imparting an anti-inflammatory phenotype. Using a mouse model of ulcerative colitis, we demonstrated that targeted deletion of RXRα in CD11c+ APCs in mice resulted in the loss of T cell homeostasis with enhanced intestinal inflammation and increased histopathological severity of colonic tissue. This was due to the increased production of proinflammatory cytokines that drive Th1/Th17 responses and decreased expression of immune-regulatory factors that promote regulatory T cell differentiation in the colon. Consistent with these findings, pharmacological activation of the RXRα pathway alleviated colitis severity in mice by suppressing the expression of inflammatory cytokines and limiting Th1/Th17 cell differentiation. These findings identify an essential role for RXRα in APCs in regulating intestinal immune homeostasis and inflammation. Thus, manipulating the RXRα pathway could provide novel opportunities for enhancing regulatory responses and dampening colonic inflammation.

Summary of a consensus conference on heart-liver transplantation.

Patients with severe heart disease may have coexisting liver disease from various causes. The incidence of combined heart-liver transplant (CHLT) is increasing as more patients with congenital heart disease survive to adulthood and develop advanced heart failure with associated liver disease from chronic right-sided heart or Fontan failure. However, the criteria for CHLT have not been established. To address this unmet need, a virtual consensus conference was organized on June 10, 2022, endorsed by the American Society of Transplantation. The conference represented a collaborative effort by experts in cardiothoracic and liver transplantation from across the United States to assess interdisciplinary criteria for liver transplantation in the CHLT candidate, surgical considerations of CHLT, current allocation system that generally results in the liver following the heart for CHLT, and optimal post-CHLT management. The conference served as a forum to unify criteria between the different specialties and to forge a pathway for patients who may need dual organ transplantation. Due to the continuing shortage of available donor organs, ethical issues related to multiorgan transplantation were also debated. The findings and consensus statements are presented.

Cost-effectiveness of goal-directed and outcome-based financial incentives for weight loss in low-income populations: the FIReWoRk randomized clinical trial.

BACKGROUND: The Financial Incentives for Weight Reduction (FIReWoRk) clinical trial showed that financial incentive weight-loss strategies designed using behavioral economics were more effective than provision of weight-management resources only. We now evaluate cost-effectiveness. METHODS: Cost-effectiveness analysis of a multisite randomized trial enrolling 668 participants with obesity living in low-income neighborhoods. Participants were randomized to (1) goal-directed incentives (targeting behavioral goals), (2) outcome-based incentives (targeting weight-loss), and (3) resources only, which were provided to all participants and included a 1-year commercial weight-loss program membership, wearable activity monitor, food journal, and digital scale. We assessed program costs, time costs, quality of life, weight, and incremental cost-effectiveness in dollars-per-kilogram lost. RESULTS: Mean program costs at 12 months, based on weight loss program attendance, physical activity participation, food diary use, self-monitoring of weight, and incentive payments was $1271 in the goal-directed group, $1194 in the outcome-based group, and $834 in the resources-only group (difference, $437 [95% CI, 398 to 462] and $360 [95% CI, 341-363] for goal-directed or outcome-based vs resources-only, respectively; difference, $77 [95% CI, 58-130] for goal-directed vs outcome-based group). Quality of life did not differ significantly between the groups, but weight loss was substantially greater in the incentive groups (difference, 2.34 kg [95% CI, 0.53-4.14] and 1.79 kg [95% CI, -0.14 to 3.72] for goal-directed or outcome-based vs resources only, respectively; difference, 0.54 kg [95% CI, -1.29 to 2.38] for goal-directed vs outcome-based). Cost-effectiveness of incentive strategies based on program costs was $189/kg lost in the goal-directed group (95% CI, $124/kg to $383/kg) and $186/kg lost in the outcome-based group (95% CI, $113/kg to $530/kg). CONCLUSIONS: Goal-directed and outcome-based financial incentives were cost-effective strategies for helping low-income individuals with obesity lose weight. Their incremental cost per kilogram lost were comparable to other weight loss interventions.

Is Robotic Surgery the Future for Resectable Esophageal Cancer?: A Systematic Literature Review of Oncological and Clinical Outcomes.

BACKGROUND: Radical esophagectomy for resectable esophageal cancer is a major surgical intervention, associated with considerable postoperative morbidity. The introduction of robotic surgical platforms in esophagectomy may enhance advantages of minimally invasive surgery enabled by laparoscopy and thoracoscopy, including reduced postoperative pain and pulmonary complications. This systematic review aims to assess the clinical and oncological benefits of robot-assisted esophagectomy. METHODS: A systematic literature search of the MEDLINE (PubMed), Embase and Cochrane databases was performed for studies published up to 1 August 2023. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols and was registered in the PROSPERO database (CRD42022370983). Clinical and oncological outcomes data were extracted following full-text review of eligible studies. RESULTS: A total of 113 studies (n = 14,701 patients, n = 2455 female) were included. The majority of the studies were retrospective in nature (n = 89, 79%), and cohort studies were the most common type of study design (n = 88, 79%). The median number of patients per study was 54. Sixty-three studies reported using a robotic surgical platform for both the abdominal and thoracic phases of the procedure. The weighted mean incidence of postoperative pneumonia was 11%, anastomotic leak 10%, total length of hospitalisation 15.2 days, and a resection margin clear of the tumour was achieved in 95% of cases. CONCLUSIONS: There are numerous reported advantages of robot-assisted surgery for resectable esophageal cancer. A correlation between procedural volume and improvements in outcomes with robotic esophagectomy has also been identified. Multicentre comparative clinical studies are essential to identify the true objective benefit on outcomes compared with conventional surgical approaches before robotic surgery is accepted as standard of practice.

Does bortezomib influence pre-transplant desensitization therapy or benefit post-heart transplant outcomes for highly sensitized patients?

BACKGROUND: The use of bortezomib which is a proteasome inhibitor has been demonstrated to be efficacious in small number of patients as a desensitization strategy in heart transplant. We reviewed our single center's experience using Bortezomib along with plasmapheresis as desensitization therapy for highly sensitized patients to assess pre- and post-transplant outcomes. METHOD: We assessed 43 highly sensitized patients awaiting HTx (defined as cPRA > 50%) between 2010 and 2021 who underwent desensitization therapy with bortezomib. Only those patients who subsequently underwent HTx were included in this study. Enrolled patients received up to four doses of bortezomib (1.3 mg/m2 ) over 2 weeks in conjunction with plasmapheresis. The efficacy of PP/BTZ was assessed by comparing the calculated panel reactive antibodies to HLA class I or class II antigens. Post-transplant outcomes including overall survival and incidence of rejection were compared to those of non-sensitized patients (PRA < 10%, n = 649) from the same center. RESULTS: The average cPRA prior to PP/BTZ was 94.5%. Post-PP/BTZ there was no statistically significant decline in mean cPRA, class I cPRA, or class II cPRA, though the average percentage decrease in class I cPRA (8.7 ± 17.0%) was higher than the change in class II cPRA (4.4 ± 13.3%). Resulted were also replicated with C1q-binding antibodies showing more effect on I class compared to class II (15.0 ± 37.4% vs. 6.8 ± 33.6%) as well as with 1:8 dilutional assay (14.0 ± 23.0% vs. 9.1 ± 34.9%). Additionally, PP/BTZ treated patients and the control group of non-sensitized patients had similar overall 1 year survival (95.4 vs. 92.5%) but patients with PP/BTZ had increased incidence of AMR (79.1% vs. 97.1%, p = < .001), any treated rejection (62.8% vs. 86.7%, p = < .001) and de novo DSA development (81.4% vs. 92.5%, p = .007). Major side effects of PP/BTZ included thrombocytopenia (42%), infection requiring antibiotics (28%), and neuropathy (12%). CONCLUSION: The use of bortezomib in highly sensitized patients does not significantly lower circulating antibodies prior to heart transplantation. However, its use may improve the chances of obtaining an immuno-compatible donor heart and contribute to acceptable post-transplant outcomes.

Genetic Deletion of LRP5 and LRP6 in Macrophages Exacerbates Colitis-Associated Systemic Inflammation and Kidney Injury in Response to Intestinal Commensal Microbiota.

Extraintestinal manifestations are common in inflammatory bowel disease and involve several organs, including the kidney. However, the mechanisms responsible for renal manifestation in inflammatory bowel disease are not known. In this study, we show that the Wnt-lipoprotein receptor-related proteins 5 and 6 (LRP5/6) signaling pathway in macrophages plays a critical role in regulating colitis-associated systemic inflammation and renal injury in a murine dextran sodium sulfate-induced colitis model. Conditional deletion of the Wnt coreceptors LRP5/6 in macrophages in mice results in enhanced susceptibility to dextran sodium sulfate colitis-induced systemic inflammation and acute kidney injury (AKI). Furthermore, our studies show that aggravated colitis-associated systemic inflammation and AKI observed in LRP5/6LysM mice are due to increased bacterial translocation to extraintestinal sites and microbiota-dependent increased proinflammatory cytokine levels in the kidney. Conversely, depletion of the gut microbiota mitigated colitis-associated systemic inflammation and AKI in LRP5/6LysM mice. Mechanistically, LRP5/6-deficient macrophages were hyperresponsive to TLR ligands and produced higher levels of proinflammatory cytokines, which are associated with increased activation of MAPKs. These results reveal how the Wnt-LRP5/6 signaling in macrophages controls colitis-induced systemic inflammation and AKI.

The RNA-binding protein AUF1 facilitates Akt phosphorylation at the membrane.

Mammalian target of rapamycin (mTOR), which is part of mTOR complex 1 (mTORC1) and mTORC2, controls cellular metabolism in response to levels of nutrients and other growth signals. A hallmark of mTORC2 activation is the phosphorylation of Akt, which becomes upregulated in cancer. How mTORC2 modulates Akt phosphorylation remains poorly understood. Here, we found that the RNA-binding protein, AUF1 (ARE/poly(U)-binding/degradation factor 1), modulates mTORC2/Akt signaling. We determined that AUF1 is required for phosphorylation of Akt at Thr308, Thr450, and Ser473 and that AUF1 also mediates phosphorylation of the mTORC2-modulated metabolic enzyme glutamine fructose-6-phosphate amidotransferase 1 at Ser243. In addition, AUF1 immunoprecipitation followed by quantitative RT-PCR revealed that the mRNAs of Akt, glutamine fructose-6-phosphate amidotransferase 1, and the mTORC2 component SIN1 associate with AUF1. Furthermore, expression of the p40 and p45, but not the p37 or p42, isoforms of AUF1 specifically mediate Akt phosphorylation. In the absence of AUF1, subcellular fractionation indicated that Akt fails to localize to the membrane. However, ectopic expression of a membrane-targeted allele of Akt is sufficient to allow Akt-Ser473 phosphorylation despite AUF1 depletion. Finally, conditions that enhance mTORC2 signaling, such as acute glutamine withdrawal, augment AUF1 phosphorylation, whereas mTOR inhibition abolishes AUF1 phosphorylation. Our findings unravel a role for AUF1 in promoting membrane localization of Akt to facilitate its phosphorylation on this cellular compartment. Targeting AUF1 could have therapeutic benefit for cancers with upregulated mTORC2/Akt signaling.

The evolving use of biomarkers in heart transplantation: Consensus of an expert panel.

In heart transplantation, the use of biomarkers to detect the risk of rejection has been evolving. In this setting, it is becoming less clear as to what is the most reliable test or combination of tests to detect rejection and assess the state of the alloimmune response. Therefore, a virtual expert panel was organized in heart and kidney transplantation to evaluate emerging diagnostics and how they may be best utilized to monitor and manage transplant patients. This manuscript covers the heart content of the conference and is a work product of the American Society of Transplantation's Thoracic and Critical Care Community of Practice. This paper reviews currently available and emerging diagnostic assays and defines the unmet needs for biomarkers in heart transplantation. Highlights of the in-depth discussions among conference participants that led to development of consensus statements are included. This conference should serve as a platform to further build consensus within the heart transplant community regarding the optimal framework to implement biomarkers into management protocols and to improve biomarker development, validation and clinical utility. Ultimately, these biomarkers and novel diagnostics should improve outcomes and optimize quality of life for our transplant patients.

Dual threshold optimization and network inference reveal convergent evidence from TF binding locations and TF perturbation responses.

A high-confidence map of the direct, functional targets of each transcription factor (TF) requires convergent evidence from independent sources. Two significant sources of evidence are TF binding locations and the transcriptional responses to direct TF perturbations. Systematic data sets of both types exist for yeast and human, but they rarely converge on a common set of direct, functional targets for a TF. Even the few genes that are both bound and responsive may not be direct functional targets. Our analysis shows that when there are many nonfunctional binding sites and many indirect targets, nonfunctional sites are expected to occur in the cis-regulatory DNA of indirect targets by chance. To address this problem, we introduce dual threshold optimization (DTO), a new method for setting significance thresholds on binding and perturbation-response data, and show that it improves convergence. It also enables comparison of binding data to perturbation-response data that have been processed by network inference algorithms, which further improves convergence. The combination of dual threshold optimization and network inference greatly expands the high-confidence TF network map in both yeast and human. Next, we analyze a comprehensive new data set measuring the transcriptional response shortly after inducing overexpression of a yeast TF. We also present a new yeast binding location data set obtained by transposon calling cards and compare it to recent ChIP-exo data. These new data sets improve convergence and expand the high-confidence network synergistically.

Microarchitectural Changes of Cardiovascular Calcification in Response to In Vivo Interventions Using Deep-Learning Segmentation and Computed Tomography Radiomics.

BACKGROUND: Coronary calcification associates closely with cardiovascular risk, but its progress is accelerated in response to some interventions widely used to reduce risk. This paradox suggests that qualitative, not just quantitative, changes in calcification may affect plaque stability. To determine if the microarchitecture of calcification varies with aging, Western diet, statin therapy, and high intensity, progressive exercise, we assessed changes in a priori selected computed tomography radiomic features (intensity, size, shape, and texture). METHODS: Longitudinal computed tomography scans of mice (Apoe-/-) exposed to each of these conditions were autosegmented by deep learning segmentation, and radiomic features of the largest deposits were analyzed. RESULTS: Over 20 weeks of aging, intensity and most size parameters increased, but surface-area-to-volume ratio (a measure of porosity) decreased, suggesting stabilization. However, texture features (coarseness, cluster tendency, and nonuniformity) increased, suggesting heterogeneity and likely destabilization. Shape parameters showed no significant changes, except sphericity, which showed a decrease. The Western diet had significant effects on radiomic features related to size and texture, but not intensity or shape. In mice undergoing either pravastatin treatment or exercise, the selected radiomic features of their computed tomography scans were not significantly different from those of their respective controls. Interestingly, the total number of calcific deposits increased significantly less in the 2 intervention groups compared with the respective controls, suggesting more coalescence and/or fewer de novo deposits. CONCLUSIONS: Thus, aging and standard interventions alter the microarchitectural features of vascular calcium deposits in ways that may alter plaque biomechanical stability.

Activation of Transcription Factor 4 in Dendritic Cells Controls Th1/Th17 Responses and Autoimmune Neuroinflammation.

Dendritic cells (DCs) are professional APCs that play a crucial role in initiating robust immune responses against invading pathogens while inducing regulatory responses to the body's tissues and commensal microorganisms. A breakdown of DC-mediated immunological tolerance leads to chronic inflammation and autoimmune disorders. However, cell-intrinsic molecular regulators that are critical for programming DCs to a regulatory state rather than to an inflammatory state are not known. In this study, we show that the activation of the TCF4 transcription factor in DCs is critical for controlling the magnitude of inflammatory responses and limiting neuroinflammation. DC-specific deletion of TCF4 in mice increased Th1/Th17 responses and exacerbated experimental autoimmune encephalomyelitis pathology. Mechanistically, loss of TCF4 in DCs led to heightened activation of p38 MAPK and increased levels of proinflammatory cytokines IL-6, IL-23, IL-1ß, TNF-α, and IL-12p40. Consistent with these findings, pharmacological blocking of p38 MAPK activation delayed experimental autoimmune encephalomyelitis onset and diminished CNS pathology in TCF4ΔDC mice. Thus, manipulation of the TCF4 pathway in DCs could provide novel opportunities for regulating chronic inflammation and represents a potential therapeutic approach to control autoimmune neuroinflammation.

A retrospective analysis of frailty status on atrial fibrillation catheter ablation outcomes.

INTRODUCTION: Catheter ablation for atrial fibrillation (AF) reduces symptoms and improves the quality of life compared with medical treatment. It is unclear if frailty impacts on the outcome of catheter ablation in patients with symptomatic AF. We sought to evaluate the association between frailty as measured by the validated NHS electronic Frailty Index (eFI) and outcomes post-AF ablation. METHODS: Two hundred forty eight patients who had undergone AF ablation with a mean age of 72.9 ± 5.16 were included in the study retrospectively. The primary endpoint for success was defined as freedom from atrial arrhythmia lasting >30 s beyond the 3-month blanking periods. Frailty was based on the eFI, and the cohort split into four groups: fit (no frailty), mild, moderate and severe frailty. RESULTS: Frailty was categorized as fit (118/248; 47.6%), mild (66/248; 26.6%), moderate (54/248; 21.8%), and severe (10/248; 4.0%). Freedom from arrhythmia occurred in 167 of 248 (67.3%) patients after a mean follow-up of 25.8 +/- 17.3 months. Fit patients had significantly greater freedom from arrhythmia (92/118; 78%) compared to mild frailty (40/66; 60.6%, p-value = .020), moderate frailty (31/54; 57.4%, p-value = .006), or severe frailty (4/10; 40.0%, p-value < .001). There was also a significant difference in arrhythmia occurrence between patients with mild frailty and severe frailty (p-value = .044). CONCLUSION: Frailty is associated with poorer outcomes in patients undergoing AF ablation. The eFI may be used in the prognostic evaluation of AF ablation outcomes. Further studies are essential to confirm the findings of this study.

The Onset and Development of Patella Alta in Children With Patellar Instability.

BACKGROUND: Patella alta is an anatomic risk factor for patellar instability in adolescents that is also linked to the risk factor of trochlear dysplasia. This study aims to determine the age of onset and age-related incidence of patella alta in a pediatric population of patients with patellar instability. We hypothesized that patellar height ratios would not increase with age, suggesting a congenital rather than the developmental origin of patella alta. METHODS: A retrospective cross-sectional cohort of patients was collected with the following inclusion criteria: patients aged 5 to 18 who had a knee magnetic resonance imaging performed from 2000 to 2022 and the International Classification of Diseases code for patellar dislocation. Demographic information and details of the patellar instability episode(s) were collected with a chart review. Sagittal magnetic resonance imaging was used to measure Caton-Deschamps Index (CDI) and the Insall-Salvati Ratio (ISR) by 2 observers. Data were analyzed to assess for associations between patellar height ratios and age of the first dislocation and to assess if the proportion of patients categorized as having patella alta changed with age. RESULTS: The 140 knees included in the cohort had an average age of 13.9 years (SD=2.40; range: 8-18) and were 55% female. Patella alta was present in 78 knees (55.7%) using CDI>=1.2 and in 59 knees (42.1%) using ISR>=1.3. The earliest age patella alta was observed was at age 8 using CDI>=1.2 and age 10 using ISR>=1.3. There were no statistically significant associations between CDI and age without adjustment ( P =0.14) nor after adjustment for sex and body mass index ( P =0.17). The proportion of knees above the CDI threshold for patella alta to the knees below the cutoff did not show a significant change with age ( P =0.09). CONCLUSIONS: Patella alta, as defined by CDI, is seen in patients as young as 8 years old. Patellar height ratios do not change with age in patients with patellar dislocation, suggesting that patella alta is established at a young age rather than developing during the adolescent years. LEVEL OF EVIDENCE: Level III-diagnostic, cross-sectional.

Immediate implantable loop recorder implantation for detecting atrial fibrillation in cryptogenic stroke.

INTRODUCTION: Atrial fibrillation (AF) is suspected as the main cause of stroke in the majority of patients presenting with cryptogenic stroke (CS). Implantable loop recorders (ILR's) are indicated for detecting AF in these patients. The short term (<1 month) and long-term AF detection rates in patients inserted with an ILR immediately after CS is reported. Secondly, we compare the safety of nurse led vs physician led ILR implantation in these patients. METHODS: This is a retrospective review of all patients who underwent inpatient ILR implantation (Medtronic Linq) between May 2020 and May 2022 at East Sussex Healthcare NHS trust. All patients were remotely monitored via the FOCUSONTM monitoring and triage service. RESULTS: A total of 186 subjects were included in the study and were followed up for a mean period of 363.0 +/- 222.6 days. The mean time between stroke and ILR was 7.0 +/- 5.5 days. The mean time between referral and ILR was 1.0 +/- 2.0 days. AF was detected in 25 (13.4%) patients. During the first 30 days of monitoring, AF was detected in 9 (4.8%) patients. The number of ILR implants performed by the specialist nurse was 107 (57.5%). There was no significant difference in the major complication rate (requiring device removal) between nurse and physician led implant (1 (0.95%) vs 0 (0%), p value = 0.389). CONCLUSION: Inpatient ILR for cryptogenic stroke is feasible. The rate of AF detection in the first month post CS is 4.8% however, more AF was detected up to one year post implant, suggesting rationale for proceeding directly to ILR implant in these patients before discharge to not delay treatment. A nurse led service is also viable with no significant difference in the major complication rate compared to physician led implants.

The charlotte large artery occlusion endovascular therapy outcome score compares favorably to the critical area perfusion score for prognostication before basilar thrombectomy.

INTRODUCTION: The Critical Area Perfusion Score (CAPS) predicts functional outcomes in vertebrobasilar thrombectomy patients based on computed tomography perfusion (CTP) hypoperfusion. We compared CAPS to the clinical-radiographic Charlotte Large artery occlusion Endovascular therapy Outcome Score (CLEOS). METHODS: Acute basilar thrombosis patients from January 2017-December 2021 were included in this retrospective analysis from a health system's stroke registry. Inter-rater reliability was assessed for 6 CAPS raters. A logistic regression with CAPS and CLEOS as predictors was performed to predict 90-day modified Rankin Scale (mRS) score 4-6. Area under the curve (AUC) analyses were performed to evaluate prognostic ability. RESULTS: 55 patients, mean age 65.8 (± 13.1) years and median NIHSS score 15.55-24, were included. Light's kappa among 6 raters for favorable versus unfavorable CAPS was 0.633 (95% CI 0.497-0.785). Increased CLEOS was associated with elevated odds of a poor outcome (odds ratio (OR) 1.0010, 95% CI 1.0007-1.0014, p<0.01), though CAPS was not (OR 1.0028, 95% CI 0.9420-1.0676, p=0.93). An overall favorable trend was observed for CLEOS (AUC 0.69, 95% CI 0.54-0.84) versus CAPS (AUC 0.49, 95% CI 0.34-0.64; p=0.051). Among 85.5% of patients with endovascular reperfusion, CLEOS had a statistically higher sensitivity than CAPS at identifying poor 90-day outcomes (71% versus 21%, p=0.003). CONCLUSIONS: CLEOS demonstrated better predictive ability than CAPS for poor outcomes overall and in patients achieving reperfusion after basilar thrombectomy.

Development of the ParaOesophageal hernia SympTom (POST) tool.

BACKGROUND: The aim of this study was to develop a symptom severity instrument (ParaOesophageal hernia SympTom (POST) tool) specific to para-oesophageal hernia (POH). METHODS: The POST tool was developed in four stages. The first was establishment of a Steering Committee. In the second stage, items were generated through a systematic review and online scoping survey of international experts. In the third stage, a three-round modified Delphi consensus process was conducted with a group of international experts who were asked to rate the importance of candidate items. An a priori threshold for inclusion was set at 80 per cent. The modified Delphi process culminated in a consensus meeting to develop the first iteration of the tool. In the final stage, two international patient workshops were held to assess the content validity and acceptability of the POST tool. RESULTS: The systematic review and scoping survey generated 64 symptoms, refined to 20 for inclusion in the modified Delphi consensus process. Twenty-six global experts participated in the Delphi consensus process. Five symptoms reached consensus across two rounds: difficulty getting solid foods down, chest pain after meals, difficulty getting liquids down, shortness of breath only after meals, and an early feeling of fullness after eating. The subsequent patient workshops deemed these five symptoms to be relevant and suggested that reflux should be included; these were taken forward to create the final POST tool. CONCLUSION: The POST tool is the first instrument designed to capture POH-specific symptoms. It will allow clinicians to standardize reporting of symptoms of POH and evaluate the response to surgical intervention.

Heart transplantation in muscular dystrophy: Single-center analysis.

INTRODUCTION: Cardiac involvement may occur in many forms of muscular dystrophy (MD). While cardiac disease may progress to warrant heart transplantation (HTx), there may be contraindications related to extra-cardiac disease including pulmonary and skeletal muscle involvement that limit overall survival and impairs post-transplant rehabilitation efforts. This study describes the MD HTx experience at a single high-volume center. METHODS: We examined the clinical characteristics and outcomes of patients with MD with heart failure (HF) (n = 28), patients with MD status post HTx (n = 20) and non-MD HTx control group (n = 40) matched 2:1 for age at transplant, sex, listing status, and antibody sensitization. RESULTS: Patients with MD who underwent HTx had increased ventilator days (2 vs. 1 days, p = .013), increased hospital length of stay (20 vs. 12 days, p = .022), and increased discharge to inpatient rehab (60% vs. 8%, p < .001). By 1 year post HTx, patients with MD more often required assistive devices for walking (55% vs. 10%, p = .01). Nonetheless, post-HTx survival was similar at 1 year (100% vs. 97.5%, p = .48) and 5 years (95.0% vs. 87.5%, p = .36). Of the HTx recipients with MD, 95% were followed by a neurologist, 60% by a neuromuscular specialist as part of the Muscular Dystrophy Association Clinic at our center. CONCLUSION: Transplantation is a feasible option for patients with MD and advanced HF. MD patients who undergo transplantation may benefit from multidisciplinary specialized care to optimize MD-related morbidity.

Heart transplant recipient 1-year outcomes during the COVID-19 pandemic.

The COVID-19 pandemic initially brought forth considerable challenges to the field of heart transplantation. To prevent the spread of the virus and protect immunocompromised recipients, our center made the following modifications to post-transplant outpatient management: eliminating early coronary angiograms, video visits for postoperative months 7, 9, and 11, and home blood draws for immunosuppression adjustments. To assess if these changes have impacted patient outcomes, the current study examines 1-year outcomes for patients transplanted during the pandemic. Between March and September 2020, we assessed 50 heart transplant patients transplanted during the pandemic. These patients were compared to patients who were transplanted during the same months between 2011 and 2019 (n = 482). Endpoints included subsequent 1-year survival, freedom from cardiac allograft vasculopathy, any-treated rejection, acute cellular rejection, antibody-mediated rejection, nonfatal major adverse cardiac events (NF-MACE), and hospital and ICU length of stay. Patients transplanted during the pandemic had similar 1-year endpoints compared to those of patients transplanted from years prior apart from 1-year freedom from NF-MACE which was significantly higher for patients transplanted during the pandemic. Despite necessary changes being made to outpatient management of heart transplant recipients, heart transplantation continues to be safe and effective with similar 1-year outcomes to years prior.

Statin Effects on Vascular Calcification: Microarchitectural Changes in Aortic Calcium Deposits in Aged Hyperlipidemic Mice.

[Figure: see text].