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In the realm of innovative medical procedures, TEER (transcatheter edge-to-edge repair) has emerged as a promising field, showcasing significant growth and advancements. Mitral TEER has been performed for the last two decades; in contrast, tricuspid TEER is newer, with long-term outcomes pending. This article aims to provide a comprehensive review of the current literature, with a primary focus on outcomes and potential complications associated with both procedures. Both procedures carry a low risk of complications when done by experienced providers. A team approach involving specialists in cardiology, cardiothoracic surgery, cardiac imaging and heart failure ensures comprehensive care. A unified approach encompassing preprocedural workup, risk assessment, and standardised care throughout the procedure and recovery contributes to successful outcomes.

Abstract An accurate assessment of p53’s functional statuses is critical for cancer genomic medicine. However, there is a significant challenge in identifying tumors with non-mutational p53 inactivation which is not detectable through DNA sequencing. These undetected cases are often misclassified as p53-normal, leading to inaccurate prognosis and downstream association analyses. To address this issue, we built the support vector machine (SVM) models to systematically reassess p53’s functional statuses in TP53 wild-type (TP53WT) tumors from multiple The Cancer Genome Atlas (TCGA) cohorts. Cross-validation demonstrated the good performance of the SVM models with a mean area under the receiver operating characteristic curve (AUROC) of 0.9822, precision of 0.9747, and recall of 0.9784. Our study revealed that a significant proportion (87%–99%) of TP53WT tumors actually had compromised p53 function. Additional analyses uncovered that these genetically intact but functionally impaired (termed as predictively reduced function of p53 or TP53WT-pRF) tumors exhibited genomic and pathophysiologic features akin to TP53-mutant tumors: heightened genomic instability and elevated levels of hypoxia. Clinically, patients with TP53WT-pRF tumors experienced significantly shortened overall survival or progression-free survival compared to those with predictively normal function of p53 (TP53WT-pN) tumors, and these patients also displayed increased sensitivity to platinum-based chemotherapy and radiation therapy.

Abstract Objective The presence of comorbidities can substantially affect patients’ quality of life, but data regarding their impact on idiopathic inflammatory myopathies (IIMs) are limited. Methods We examined the prevalence of comorbidities in IIM patients, other autoimmune rheumatic diseases (oAIRDs) and healthy controls (HCs), using data from the self-reported COVAD-2 survey. We defined basic multimorbidity (BM) as the presence of ≥2 non-rheumatic chronic conditions and complex multimorbidity (CM) as the presence of ≥3 non-rheumatic chronic conditions affecting ≥3 organ systems. Hierarchical clustering on principal components was performed for grouping. Results Among the COVAD respondents, 1558 IIMs, 4591 oAIRDs and 3652 HCs were analysed. IIMs exhibited a high burden of comorbidities (odds ratio [OR]: 1.62 vs oAIRDs and 2.95 vs HCs, P < 0.01), BM (OR: 1.66 vs oAIRDs and 3.52 vs HCs, P < 0.01), CM (OR: 1.69 vs AIRDs and 6.23 vs HCs, P < 0.01) and mental health disorders (MHDs) (OR: 1.33 vs oAIRDs and 2.63 vs HCs, P < 0.01). Among the IIM patients, those with comorbidities or MHDs had lower PROMIS Global Physical (PGP), PROMIS Global Mental (PGM), and PROMIS Physical Function (SF10) scores, and higher fatigue (F4a) scores (all P < 0.001). PGP, PGM, SF10a and F4a were influenced by age, active disease, BM and MHDs. Four distinct clusters were identified among the IIMs according to comorbidities and PROMIS scores. Conclusion Patients with IIMs have a higher burden of comorbidities that influence physical and mental health, identifiable as clinical clusters for optimized and holistic management approaches.

Background: Conventional neoadjuvant chemoradiotherapy (nCRT) yields a pathologic complete response (pCR) rate of 15–30% for locally advanced rectal cancer (LARC). This study ventures to shift this paradigm by incorporating short-course nCRT with immunotherapy, specifically Envafolimab, to achieve improved treatment efficacy and possibly redefine the standard of care for LARC. Materials and methods: The PRECAM study is a prospective, single-arm, phase 2 clinical trial for LARC in patients with microsatellite stable (MSS) tumors. Participants received short-course radiotherapy (25Gy/5f), followed by two cycles of CAPEOX chemotherapy and six weekly doses of Envafolimab, a PD-L1 antibody, before total mesorectal excision surgery. The primary endpoint was the pCR rate. Results: From April to December 2022, 34 patients were enrolled, of whom 32 completed the study, each diagnosed with an MSS rectal adenocarcinoma. All patients underwent preoperative CRT combined with Envafolimab. Remarkably, a pCR rate of 62.5% (20/32) was attained, and a significant pathologic response rate of 75% (24/32) was achieved. Additionally, 21 of 32 participants achieved a neoadjuvant rectal (NAR) score below 8, suggesting an effective treatment response. Common adverse events included tenesmus (78.1%), diarrhea (62.5%), and leukocyte decrease (40.6%). Two Grade 3 adverse events were noted, one related to liver function abnormality and the other to a decrease in platelet count. Surgical procedures were performed in all cases, with minor complications, including ileus, infections, and anastomotic leakage. As of this report, there have been no reported cases of recurrence or death during the follow-up period, ranging from 12 to 20 months. Conclusion: In LARC patients exhibiting MSS tumors, combining short-course nCRT with Envafolimab demonstrated favorable efficacy, leading to a significant pCR rate. Minor adverse effects and surgical complications were observed. These preliminary but promising results underscore the potential of this approach and call for further exploration and validation through a randomized controlled trial.

Abstract INTRODUCTION Although frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype. METHODS Retrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments. RESULTS Common symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word‐finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face‐recognition deficits (60%). Real‐life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations. DISCUSSION This study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real‐life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients. Highlights This project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.

AbstractBackgroundPhosphide metal poisoning results in tens of thousands of fatalities per year worldwide. The mortality in critically ill patients often exceeds 50%. The available treatment is supportive and there is no antidote. Dialysis is recommended to treat advanced complications but has not been prescribed early in the process. In this study we report our experience in using dialysis in the early hours of presentation of the patients and suggest it can favorably improve the prognosis. We also draw attention to the risk of suicide under conditions of chronic conflict such as those in northwestern Syria, and to the lack of necessary mental health support for patients after suicide attempts.MethodsRetrospective review of records of patients poisoned with aluminum phosphide and admitted to critical care facilities in northwestern Syria between July 2022 and June 2023.ResultsDuring the observation period 16 cases were encountered. Suicide was the reason of the poisoning in 15 patients, the median patient age was 18 years and over two thirds of the patients were female. Early dialysis was used in 11 patients who were critically ill and their mortality rate was 18%.ConclusionsPhosphide metal poisoning is common in the disasters stricken area of northwestern Syria. Most cases are suicidal and impact young females. Early dialytic interventions may favorably impact the outcomes.

Purpose of review The major fighting activities in the Syrian conflict have subsided, but the country continues to deal with significant political, economic, and psychosocial consequences that gravely impact the healthcare system, including the care of patients with kidney disease. The purpose of this manuscript is to review some of the problems faced by kidney patients in postconflict Syria and their available and proposed remedies. Recent findings Many challenges, such as unfair, poorly planned, and poorly organized distribution of resources, suboptimal quality-monitoring infrastructure, psychosocial barriers, and workforce shortages, impede the delivery of quality care and negatively impact outcomes. The negative impact of these problems is not uniform and tends to affect certain areas more than others because of geopolitical factors imposed by the conflict. Summary After prolonged conflicts, healthcare resources remain limited for prolonged periods, leading to inadequate care, poor outcomes, and worsening inequities. Involvement of the international community and expatriate nephrologists is essential to guide care delivery and improve outcomes. The lessons learned from the Syrian conflict apply to many limited resources and disaster situations.

3614 Background: Conventional neoadjuvant chemoradiotherapy (nCRT) yields a pathologic complete response (pCR) rate of about 15%–- 30% for locally advanced rectal cancer (LARC). This PRECAM study aimed to investigate the efficacy and safety of neoadjuvant short-course radiotherapy combined with CAPEOX plus Envafolimab in Patients with Microsatellite Stable (MSS) LARC, redefining the standard of care (SOC) for LARC. Methods: The study is an open-label, prospective, single-arm, phase II clinical study . Eligible patients with MSS LARC were consecutively enrolled. Participants received short-course radiotherapy (25Gy/5f) with subsequent two cycles of CAPEOX (capecitabine and oxaliplatin) and 6 cycles of Envafolimab (subcutaneous injection, 150 mg, QW ) followed by total mesorectal excision surgery. The primary endpoint was pathological complete response (pCR) rate, and the secondary endpoint was major pathologic (MPR) rate and safety. Results: From April to December 2022, 34 patients were enrolled, of whom 32 completed the study. Remarkably, The pCR rate was62.5% (20/32), and the (MPR) rate was 75% (24/32). Furthermore, 65.6% (21/32) patients achieved a neoadjuvant rectal (NAR) score below 8, suggesting an effective treatment response. Common adverse events included tenesmus (78.1%), diarrhea (62.5%), and leukocyte decrease (40.6%), with two cases of Grade 3 adverse events. Surgical procedures were performed in all 32 cases, with minor complications observed. During the follow-up period of up to 20 months, no recurrence or death were reported. Conclusions: Short-course radiotherapy combined with CAPEOX plus Envafolimab showed favorable pCR rate with manageable adverse effects and surgical complications in LARC, underscoring the potential of the combination therapy for MSS LARC. A Randomized controlled trial is warranted for further exploration and validation. Clinical trial information: NCT05216653 .

SUMMARY Transcriptome‐wide association studies (TWAS) can provide single gene resolution for candidate genes in plants, complementing genome‐wide association studies (GWAS) but efforts in plants have been met with, at best, mixed success. We generated expression data from 693 maize genotypes, measured in a common field experiment, sampled over a 2‐h period to minimize diurnal and environmental effects, using full‐length RNA‐seq to maximize the accurate estimation of transcript abundance. TWAS could identify roughly 10 times as many genes likely to play a role in flowering time regulation as GWAS conducted data from the same experiment. TWAS using mature leaf tissue identified known true‐positive flowering time genes known to act in the shoot apical meristem, and trait data from a new environment enabled the identification of additional flowering time genes without the need for new expression data. eQTL analysis of TWAS‐tagged genes identified at least one additional known maize flowering time gene through trans ‐eQTL interactions. Collectively these results suggest the gene expression resource described here can link genes to functions across different plant phenotypes expressed in a range of tissues and scored in different experiments.