Citations

Introduction: Redo-Surgical valve replacement (Redo-SAVR) is the gold standard treatment for failed degenerated bioprosthetic valves. Recently approved less invasive Valve-In-Valve Transcatheter Aortic Valve Implantation (ViV-TAVI) procedure is becoming more popular but with limited evidence of its safety and efficacy compared to redo-SAVR. Hypothesis: We aimed to conduct the meta-meta analysis to evaluate the outcomes of ViV-TAVI compared to redo-SAVR. Methods: We conducted a systematic search of meta-analysis studies assessing outcomes of ViV-TAVR vs redo-SAVR using PubMed search engine and following PRISMA guidelines from inception to May 2021. A meta-meta-analysis was performed by obtaining a pooled odds ratio, 95% confidence interval (95%CI) using random-effects models to analyze outcomes of 30-day all-cause mortality and procedural mortality. Results: Nine meta-analysis studies were included. We found that there was a significantly lower odds of 30-day all-cause mortality (pooled OR:0.60; 95%CI:0.53-0.68; p<0.00001) with 0% heterogeneity (I2= 0%;p=0.53) in the ViV-TAVI compared to redo-SAVR. We also found a reduced risk of procedural mortality with ViV-TAVI compared to redo-SAVR (pooled OR:0.52; 95%CI:0.27-0.98; p=0.04) with 0% heterogeneity (I2= 0%;p=0.69) (Figure). Conclusions: ViV-TAVI is significantly associated with reduced risk of 30-day all-cause mortality, and procedural mortality compared to redo-SAVR. Our meta-meta-analysis supports that minimally invasive ViV-TAVI is a safe and better procedure for degenerated bioprosthetic valves in high-risk candidates.

AbstractThe Ehlers–Danlos Syndromes (EDS) are a group of inherited connective tissue disorders with a worldwide prevalence of 1 in 2500 to 1 in 5000 births irrespective of sex or ethnicity. Fourteen subtypes of Ehlers–Danlos Syndrome (EDS) have been described, each with characteristic phenotypes and associated genes. Pathogenic variants in COL5A1 and COL5A2 cause the classical EDS subtypes. Pathogenic variants in COL3A1 cause vascular EDS. In this case report, we describe a patient with a phenotype resembling that of vascular EDS, caused by a novel pathogenic variant in COL5A1.

The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions, consisting of medical and hematologic oncologists with expertise across a wide range of disease sites, and experts from the areas of dermatology, gastroenterology, endocrinology, neurooncology, nephrology, cardio-oncology, ophthalmology, pulmonary medicine, and oncology nursing. The content featured in this issue is an excerpt of the recommendations for managing toxicities related to CAR T-cell therapies and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to immune checkpoint inhibitors, visitNCCN.org.

Hepatic adenomas occur most commonly in women between the ages of 20 and 40 years, but rarely they occur in older aged persons, including those 60 years of age or older. This group of adenomas, however, has not been systemically examined. Twenty-six hepatic adenomas in persons 60 years of age or older were studied, along with a control group of 50 hepatic adenomas in persons aged 30 to 39. Hepatic adenomas in persons 60 or more years of age were found in 21 women and 5 men, while the control group had 44 women and 6 men. Subtyping the adenomas in persons 60 years or older showed the following results: 18 HNF1A-inactivated adenomas (69%), 4 inflammatory adenomas (15%), and 4 unclassified adenomas (15%). In contrast, the control group showed a significantly different pattern (P=0.003), with a greater percentage of inflammatory adenomas (28, 56%), fewer HNF1A-inactivated adenomas (8, 16%), and more unclassified adenomas (14, 28%). Atypia and malignant transformation within the hepatic adenomas was studied next. Of the hepatic adenomas in persons age 60 or greater, 3 (12%) showed atypical histologic features, and 6 (23%) had a malignant transformation. In contrast, for hepatic adenomas in the control group, only 4 (8%) adenomas showed atypical histologic features, and 3 (6%) had undergone malignant transformation. In addition, the hepatic adenomas that were atypical or showed early malignant transformation were less likely to have beta-catenin activation in patients over 60 (2/9 cases) compared with those between 30 and 39 years (5/7 cases). Myxoid change and heavy lipofuscin deposition were also more common in adenomas in older aged persons. In conclusion, hepatic adenomas in persons 60 years of age or older are enriched for HNF1A-inactivated adenomas and have a higher frequency of malignant transformation. Malignant transformation, however, is less likely to develop through activation of the beta-catenin pathway.

Introduction: Right ventricle (RV) dysfunction linked with acute Pulmonary embolism (PE) is associated with significant mortality. Several studies have documented use of RV free wall strain (RVS) for assessing mortality, but RV free wall systolic (RVSRs) and early diastolic strain rate (RVSRe) have not been explored. Hypothesis: The study aims to assess the RV function in longitudinal domain of contractility using 2 D speckle tracking echocardiography and evaluate if it was able to predict all-cause mortality at 30 days. Methods: This is a single center prospective study done between November 2012 to June 2020. 293 adult patients with acute PE having echocardiogram performed within 24 hours were enrolled and baseline comorbidities were recorded. 2 D Speckle tracking echocardiography was performed offline. Multiple logistic regression analyses and ROC were performed to evaluate if RV Strain (RVS) and strain rate (systolic-SRs, early diastolic-SRe) were able to predict all-cause mortality at 30 days. Results: Mean age was 65 ± 15 years, 60.7 % males and 41% had coronary artery disease, 29% had cancer and 11% had COPD. Mean free wall (FW) RVS was -19.7±7.7%, FW RV SRs was -0.9±0.4 s -1 , FW RV SRe was 0.8±0.3 s -1 . (Figure A) All-cause mortality was present in 11 patients (3.8%) at 30 days, 17 (5.8%) at 3 months and 29 (9.9%) at 6 months. In the Univariate analysis, FW RVS and FW RVSRs were significantly associated with 30 days all-cause, but after adjusting for age, cancer, and COPD, only FW RVSRs remains significant (p=0.02) with an AUC to predict 30-day all-cause mortality of 0.73 (95% CI 0.54-0.88) a cut-off value of -0.7 had a sensitivity of 73% and specificity of 64% (Figure B) Conclusions: The study demonstrated that RV Free wall SRs measured by 2 D STE is a good prognostic indicator for 30 days all-cause mortality in patients with acute PE. This novel modality could be used for risk stratification in the setting of acute PE.

Introduction: Subclinical cardiovascular involvement in COVID-19 patients has not been well described. 2D-Speckle Tracking Echocardiography derived global longitudinal strain (GLS) and systolic and early diastolic strain rate (SRs, SRe) measurements are more sensitive than standard echocardiographic parameters to diagnose subclinical mechanical dysfunction in patients with normal Left Ventricle Ejection Fraction (LVEF). Hypothesis: Evaluate subclinical myocardial mechanical function and reserve in active COVID-19 systemic disease patients with normal LVEF vs controls and between survivors and non survivors of COVID-19 in the longitudinal domain of contractility. Methods & Results: 166 adult patients with active COVID 19 having normal LVEF were included and compared to 89 healthy volunteers. Baseline parameters were recorded. Peak GLS, SRs and SRe, were measured offline. Mean age was 62.53 ± 18.96 years and 87 (52%) were males and Mean LVEF was 62±5%. COVID-19 patients had higher GLS compared to controls (-20.93%±0.30 vs. -18.48%±0.40; p value <0.0001), SRs was similar (-0.97 s -1 ±0.10 vs. -0.98 s -1 ±0.02, p value 0.2528) and SRe was lower (0.85 s -1 ±0.0 vs. 1.05 s -1 ±0.02; p value <0.0001) respectively. After adjusting for age and sex, GLS, SRs and SRe was significant (p<0.001). GLS, SRs and SRe were similar in survivors vs. non survivors (p NS), both groups had elevated biomarkers (cardiac troponin, NT-pro BNP, CRP), but non survivors had higher levels (3.22±0.18 vs 3.62±0.28, p = 0.2371, 5.86±0.19 vs 7.15±0.27, p = 0.0004, 3.75±0.14 vs 4.31±0.21, p = 0.0422, 7.64±0.17 vs 8.26±0.25, p=0.0487 respectively) (Table 1). Conclusions: In our cohort, COVID-19 patients had better systolic reserve and abnormal relaxation compared to controls. There was no significant difference in strain (GLS) and strain rate (SRs & SRe) amongst survivors and non survivors in the longitudinal domain of contractility despite of higher inflammatory biomarkers in non-survivors.

Background: Bariatric surgery (BS) has been shown to be beneficial in improving co-morbid conditions in morbidly obese patients. Long-term cardiovascular complications remain undefined and warrant further investigation. We examined the prevalence and risk of atrial fibrillation (AF) in obese patients who underwent BS. Methods: PUBMED/Medline, SCOPUS, EMBASE databases were systematically reviewed using relevant keywords to search prospective and retrospective studies reporting AF with long-term (at least >1-year follow-up) follow-up in patients who had undergone BS. Random effects models were used for meta-analysis and subgroup analysis. I 2 statistics was used to identify substantial (>75%) heterogeneity. Results: Nine studies (3 USA, 2 UK, 4 Sweden) including 24,164 patients who had undergone BS (mean BMI cut off: 35, mean age 42 years) with 29,330 controls were included in the analysis with a median follow-up of 8 years. Pooled prevalence of AF was lower in BS arm (3.0%, 95%CI: 1.4%-5%) as compared to non-BS arm (3.8%, 95% CI: 1.8%-5.0%). The Forest Plot (Fig. 1) depicts significantly reduced odds of having AF in patients who have undergone BS vs controls (OR: 0.74, 95%CI: 0.60-0.91, I 2 =70.2%, p<0.01). Sensitivity analysis using the leave-one-out method did confirm equivalent results. On subgroup analysis, AF prevalence in the BS group was slightly higher in studies with a mean age of ≥50 years (4.8%, 0-12%) as compared to cohorts with mean age <50 (2.0%, 1.4-5.0%). The pooled rate of AF was low on short-term follow-up compared to long-term follow-up after BS: 1.5% (0.9-2.5%) in 1-5 years, 1.9% (0.2-4.5%) in 6-10 years, 5.4% (0-13.9%) ≥10 years of BS. Conclusions: Obese patients undergoing BS had nearly 25% lower risk and lower pooled rate of AF when compared to controls over 8 years of follow-up. The protective effect of BS on reduced risk of AF was seen to gradually wane over longer follow-up which warrants continued efforts to effectively control CVD risk factors.

ABSTRACT Background and Objective Patients with dementia with Lewy bodies (DLB) may have overlapping Alzheimer's disease pathology. We investigated the longitudinal rate of tau accumulation and its association with neurodegeneration and clinical disease progression in DLB. Methods Consecutive patients with probable DLB (n = 22) from the Mayo Clinic Alzheimer's Disease Research Center and age‐matched and sex‐matched cognitively unimpaired controls (CU; n = 22) with serial magnetic resonance imaging and flortaucipir positron emission tomography scans within an average of 1.6 years were included. Regional annualized rates of flortaucipir uptake standardized uptake value ratios (SUVr) were calculated. Regional annualized rates of cortical volume change were measured with the Tensor Based Morphometry–Syn algorithm. Results The annual increase of flortaucipir SUVr was greater in the middle and superior occipital, fusiform, and inferior parietal cortices in DLB (mean: 0.017, 0.019, 0.019, and 0.015, respectively) compared with the CU (mean: −0.006, −0.009, −0.003, and − 0.005, respectively; P < 0.05). In patients with DLB (but not the CU), a longitudinal increase in flortaucipir SUVr was associated with longitudinal cortical atrophy rates in the lateral occipital and inferior temporoparietal cortices, hippocampus, and the temporal pole as well as a concurrent decline on Mini‐Mental State Examination and Clinical Dementia Rating–Sum of Boxes in the lateral occipital and the fusiform cortices. Conclusions Tau accumulation was faster in DLB compared with the CU, with increased accumulation rates in the lateral occipital and temporoparietal cortices. These increased rates of tau accumulation were associated with neurodegeneration and faster disease progression in DLB. Tau may be a potential treatment target in a subset of patients with DLB. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Abstract Foxp3⁺ regulatory T cells (Tregs) maintain immune homeostasis, yet the process that preserves their stability during aging remain unclear. Mechanistic progress has been hindered by models that ablate Tregs or delete Foxp3 , which induce acute autoimmunity and prevent longitudinal study of physiological regulatory drift. Here, we establish a dose-dependent mitochondrial framework that preserves Treg lineage survival while permitting gradual metabolic attenuation. Using Treg-restricted TFAM modulation, a complementary haploinsufficient model, and whole-spleen single-cell profiling. We identify lineage-selective immune remodeling characterized by contraction of naïve CD8⁺ and follicular B-cell pools, alteration of CD4⁺ states, expansion of activated Tregs, and emergence of neuroimmune stress linked transcriptional modules that parallel physiological aging. Mechanistically, mitochondrial insufficiency is associated with functional loss of FOXP3- centered chromatin coordination and enrichment of NF-κB/NFAT/AP-1 inflammatory and senescence programs while lineage identity remains detectable. Partial mitochondrial attenuation within Tregs alone is sufficient to drive chronic low-grade systemic inflammation, neuromuscular decline, gut microbial restructuring, and elevated microglial responsiveness without Treg depletion. Pharmacologic and microbiota-directed interventions partially reduce inflammatory tone and improve functional metrics. Together, our findings identify TFAM as a key regulator of immune aging and reveal that healthy mitochondrial function in Tregs is essential for protecting against inflammaging and age-associated functional decline.

Lymphoma is the most common hematologic malignancy comprising a diverse group of neoplasms arising from multiple blood cell lineages. Any structure of the thorax may be involved at any stage of disease. Imaging has a central role in the initial staging, response assessment, and surveillance of lymphoma, and updated standardized assessment criteria are available to assist with imaging interpretation and reporting. Radiologists should be aware of the modern approaches to lymphoma treatment, the role of imaging in posttherapeutic surveillance, and manifestations of therapy-related complications.