EWSR1::ATF1 fusions characterize a group of extra-abdominal epithelioid and round cell mesenchymal neoplasms, phenotypically overlapping with sclerosing epithelioid fibrosarcomas, and intra-abdominal FET::CREB fusion neoplasms.

With the increasing use of next generation sequencing in soft tissue pathology, particularly in neoplasms not fitting any World Health Organization (WHO) category, the spectrum of EWSR1 fusion-associated soft tissue neoplasms has been expanding significantly. Although recurrent EWSR1::ATF1 fusions were initially limited to a triad of mesenchymal neoplasms including clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma and malignant gastrointestinal neuroectodermal tumor (MGNET), this family has been expanding. We herein describe 4 unclassified extra-abdominal soft tissue (n = 3) and bone (n = 1) neoplasms displaying epithelioid and round cell morphology and carrying an EWSR1::ATF1 fusion. Affected were 3 males and 1 female aged 20-56 years. All primary tumors were extra-abdominal and deep-seated (chest wall, mediastinum, deltoid, and parapharyngeal soft tissue). Their size ranged 4.4-7.5 cm (median, 6.2). One patient presented with constitutional symptoms. Surgery with (2) or without (1) neo/adjuvant therapy was the treatment. At last follow-up (8-21 months), 2 patients developed progressive disease (1 recurrence; 1 distant metastasis). The immunophenotype of these tumors is potentially misleading with variable expression of EMA (2 of 3), pankeratin (2 of 4), synaptophysin (2 of 3), MUC4 (1 of 3), and ALK (1 of 3). All tumors were negative for S100 and SOX10. These observations point to the existence of heretofore under-recognized group of epithelioid and round cell neoplasms of soft tissue and bone, driven by EWSR1::ATF1 fusions, but distinct from established EWSR1::ATF1-associated soft tissue entities. Their overall morphology and immunophenotype recapitulate that of the emerging EWSR1/FUS::CREB fusion associated intra-abdominal epithelioid/round cell neoplasms. Our cases point to a potentially aggressive clinical behavior. Recognizing this tumor type is mandatory to delineate any inherent biological and/or therapeutic distinctness from other, better-known sarcomas in the differential diagnosis including sclerosing epithelioid fibrosarcoma.

Multidisciplinary approach in resection of stage IIIA lung cancer with severe aortic stenosis: A case report.

Thoracic surgery in the context of complex multimorbidity and clinical deterioration presents a unique set of challenges when balancing risk and benefit. Advances in anaesthesia, surgical technique, and imaging, have allowed for operative options for patients that were once deemed too high-risk. An effective proactive multi-disciplinary approach is essential for successful outcomes. We report the case of a 65-year-old patient with a background of severe aortic stenosis who underwent lung resection for stage IIIA lung cancer, where pivotal multi-disciplinary team input from the anaesthetic, surgery, critical care and radiology teams, clarified the cause of his clinical deterioration, contributed to decisions over his management and ensured a good clinical outcome.

Alteration of glucose metabolism and expression of glucose transporters in ovarian cancer.

Aerobic glycolysis also known as the Warburg effect, remains a hallmark of various cancers, including ovarian cancer. Cancer cells undergo metabolic changes to sustain their tumorigenic properties and adapt to environmental conditions, such as hypoxia and nutrient starvation. Altered metabolic pathways not only facilitate ovarian cancer cells' survival and proliferation but also endow them to metastasize, develop resistance to chemotherapy, maintain cancer stem cell phenotype, and escape anti-tumor immune responses. Glucose transporters (GLUTs), which play a pivotal role as the rate-limiting step in glycolysis, are frequently overexpressed in a variety of tumors, including ovarian cancer. Multiple oncoproteins can regulate GLUT proteins, promoting tumor proliferation, migration, and metastasis, either dependent or independent of glycolysis. This review examines the alteration of GLUT proteins, particularly GLUT1, in ovarian cancer and its impact on cancer initiation, progression, and resistance to treatment. Additionally, it highlights the role of these proteins as biomarkers for diagnosis and prognosis in ovarian cancer, and delves into novel therapeutic strategies currently under development that target GLUT isoforms.

Benign metastasizing fumarate hydratase (FH)-deficient uterine leiomyomas: clinicopathological and molecular study with first documentation of multi-organ metastases.

Leiomyoma is the most prevalent benign tumor of the female reproductive system. Benign metastasizing leiomyoma (BML) is a rare phenomenon that presents at distant sites, typically the lungs, exhibiting histopathological features similar to the primary uterine tumor in the absence of malignancy features in both. Fumarate hydratase-deficient uterine leiomyoma (FH-d UL) is an uncommon subtype among uterine smooth muscle tumors (0.5-2%), showing distinctive histomorphology and FH inactivation. The majority of FH-d ULs are sporadic, caused by somatic FH inactivation, while a minority of cases occur in the context of the hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome caused by germline FH inactivation. Metastasizing FH-d UL has not been well documented and might be under-reported. Here, we present two cases (21- and 34-year-old females) who presented with metastasizing FH-d UL after myomectomy/hysterectomy with histologically proven multiple lung metastases in both, in addition to multi-organ involvement in one case (cervical-thoracic lymph nodes, left kidney, perihepatic region, left zygomatic bone, and soft tissues). Pathological examination confirmed FH-d leiomyomas in the primary/recurrent uterine tumors, multiple lung lesions, and a renal mass. The minimal criteria for diagnosis of leiomyosarcoma were not fulfilled. Genetic testing revealed germline pathogenic FH variants in both cases (c.1256C > T; p.Ser419Leu in Case 1 and c.425A > G; p.Gln142Arg in Case 2). These novel cases highlight a rare but possibly under-recognized presentation of FH-d BML. Our study suggests that FH-d BML cases might be enriched for the HLRCC syndrome.

Codeveloping theories of change for improved community-based violence intervention evaluation.

BACKGROUND: Community-based violence intervention (CVI) programs are considered important strategies for preventing community violence and promoting health and safety. Mixed and inconclusive results from some prior CVI evaluations, as well as our general lack of understanding about the reasons for such varied findings, may be explained in part by misalignment of program theories of change and evaluation measures. Furthermore, most prior evaluations have focused solely on deficit-based outcomes; this narrow focus is inconsistent with the premise of CVI and may fail to capture improvements in health and well-being that are on the hypothesized pathway from intervention to violence reduction. METHODS: This article describes the process and results of codeveloping a theory of change for community-based youth firearm violence intervention and prevention programs in Washington state through a community-researcher partnership. We followed a multistep iterative process, involving (1) CVI program documentation review, (2) individual meetings, and (3) a day-long workshop. RESULTS: The theory of change included six key domains: (1) root causes, (2) promotive factors, (3) activities, (4) intermediate outcomes, (5) longer-term outcomes, and (6) multilevel context (youth/family, staff/organizational, community, and societal). Root causes were social and structural drivers of community violence. Promotive factors were assets and resources among the community, youth/their families, and community organizations that promote health and safety. Activities were supports and services the program provided to youth and their families, staff, and, potentially, the broader community. Intermediate and longer-term outcomes were the changes among youth, their families, staff, and the community that resulted from program activities. Intermediate outcomes may be felt within 6 months to 1 year, and longer-term outcomes may be felt after 1 to 2 years and beyond. CONCLUSION: The theory of change we codeveloped provides a common lens to conceptualize, compare, and evaluate CVI programs in Washington state and may support more rigorous and equity-centered evaluations. LEVEL OF EVIDENCE: Diagnostic Test/Criteria; Level V.

The Danish lung cancer registry: A nationwide validation study.

BACKGROUND: This study evaluates the validity of the information in the Danish Lung Cancer Registry (DLCR). Since 2000, the DLCR has been a tool for monitoring interventions and outcome of all Danish lung cancer patients with the intent to streamline and improve treatment and survival. The DLCR receives information from the Danish Patient Registries in addition to clinical information from the treating physicians. In the year 2022, more than 50 papers have been published using DLCR as a data source. However, the DLCR has not previously been validated. METHODS: A random sample of 1000 patients diagnosed with non-small cell lung cancer from 2014 to 2016 and recorded in the DLCR were included for validation. Medical records were reviewed and were considered as the "gold standard" to which data listed in the DLCR were compared. RESULTS: Information was retrieved from medical charts for all patients. Agreement on stage at diagnosis was 90.1 % (95 % CI 88.0-91.9) and on date of diagnoses was 93.8 (95 % CI 92.1-93.2). Agreement on smoking status in pack years (+/- 10 pack years) was 91.2 % (95 % CI 88.6-93.2). The positive predictive value of treatment intent was 87.4 (95 % CI 85.1-89.6). CONCLUSION: The data in the DLCR are complete, detailed and accurate. The comparison of data from the DLCR with the medical records revealed overall high validity of the data in the registry.

The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants.

We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-α T cell receptor (pre-TCRα) expression. Low circulating naive αß T cell counts at birth persisted over time, with normal memory αß and high γδ T cell counts. Their TCRα repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue αß T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naive αß T cell counts but high γδ T cell counts. Although residual pre-TCRα expression drove the differentiation of more αß T cells, autoimmune conditions were more frequent in these patients compared with the general population.

Outcomes with allogeneic hematopoietic stem cell transplantation in TP53-mutated myelodysplastic syndrome: A systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to evaluate outcomes after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in TP53-mutated myelodysplastic syndromes (MDS). A literature search was performed on PubMed, Cochrane, Embase, and Clinicaltrials.gov. After screening 626 articles, eight studies were included. Data were extracted following the PRISMA guidelines and analyzed using the meta-package by Schwarzer et al. We analyzed 540 patients. The pooled median 3 (1-5) year overall survival was 21% (95% CI 0.08-0.37, I2=91%, n=540). The pooled relapse rate was 58.9% (95% CI 0.38-0.77, I2=93%, n=487) at a median of 1.75 (1-3) years. The pooled 4-year progression- free survival was 34.8% (95% CI 0.15-0.57, I2=72%, n=105). Outcomes of Allo-HSCT for TP53-mutated MDS patients remain poor, with 21% OS at three years; however, Allo-HSCT confers a survival advantage as compared to non-transplant palliative therapies. Our findings suggest the need to explore novel therapeutic agents in prospective clinical trials.

Top Ten Tips Palliative Care Clinicians Should Know About Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Rapidly proliferating leukemic cells cause symptoms and increase the risk of infection. While individuals may initially benefit from supportive measures, disease-directed therapy may ultimately be required for symptom management, even at the end of life, although this may also inadvertently increase symptom burden. This unpredictable illness trajectory complicates prognostic uncertainty and the timing of hospice referral, which may prohibit access to palliative therapies and lead to recurrent hospitalizations. However, emerging evidence demonstrates that early palliative care (PC) integration with standard leukemia care results in improved quality of life, psychological outcomes, and greater participation in advance care planning. To orient PC clinicians asked to care for patients with AML, this article highlights 10 salient considerations.

The Tumor Suppressor BRCA1/2, Cancer Susceptibility and Genome Instability in Gynecological and Mammary Cancers.

BRCA1 and BRCA2 germline alterations highly predispose women to breast and ovarian cancers. They are mostly found within the TNBC (Triple-Negative Breast Cancer) and the HGSOC (High-Grade Serous Ovarian Carcinoma) subsets, known by an aggressive phenotype, the lack of therapeutic targets and poor prognosis. Importantly, there is an increased risk for cervical cancer in BRCA1 and BRCA2 mutation carriers that raises questions about the link between the HPV-driven genome instability and BRCA1 and BRCA2 germline mutations. Clinical, preclinical, and in vitro studies explained the increased risk for breast and ovarian cancers by genome instability resulting from the lack or loss of many functions related to BRCA1 or BRCA2 proteins such as DNA damage repair, stalled forks and R-loops resolution, transcription regulation, cell cycle control, and oxidative stress. In this review, we decipher the relationship between BRCA1/2 alterations and genomic instability leading to gynecomammary cancers through results from patients, mice, and cell lines. Understanding the early events of BRCA1/2-driven genomic instability in gynecomammary cancers would help to find new biomarkers for early diagnosis, improve the sensitivity of emerging therapies such as PARP inhibitors, and reveal new potential therapeutic targets.

Health related quality of life in adults after late repair of tetralogy of fallot: experience from a low-middle income country.

PURPOSE: Without neonatal screening in low middle-income countries like Pakistan, Tetralogy of Fallot (TOF) is a congenital heart disease which frequently remains untreated beyond infancy. The purpose of this study is to determine and assess outcomes and health related quality of life (HRQOL) in patients who undergo complete repair of TOF as adults. METHODS: 56 patients who underwent complete TOF repair after 16 years of age were included. Patient data was collected via retrospective chart review, and a semi structured interview along with Short-Form 36 (SF-36) questionnaire were used to assess HRQOL. RESULTS: 66.1% of patients were male with the mean age at surgery of 22.3 ± 6.00. All patients had a post-operative NYHA Classification of I or II, 94.6% had an ejection fraction of ≥ 50% and 28.6% showed small residual lesions in follow-up echocardiograms. 32.1% of patients suffered post-operative morbidity. For the quantitative assessment using SF-36 scores, patients showed good scores of median 95 (65-100). A major cause of delay to treatment was lack of consensus between treatments offered by doctors in different parts of Pakistan. There was a pattern of 'inability to fit in' among patients who had had late TOF repair, despite self- reported improved HRQOL. CONCLUSION: Our results indicate that even with a delayed diagnosis, surgical repair of TOF produces good functional results. However, these patients face significant psychosocial issues. While early diagnosis remains the ultimate goal, patients undergoing late repair should be managed in more holistic manner with attention to psychological impact of the disease as well.

Outcomes with chimeric antigen receptor t-cell therapy in relapsed or refractory acute myeloid leukemia: a systematic review and meta-analysis.

Background: We conducted a systematic review and meta-analysis to evaluate outcomes following chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory acute myeloid leukemia (RR-AML). Methods: We performed a literature search on PubMed, Cochrane Library, and Clinicaltrials.gov. After screening 677 manuscripts, 13 studies were included. Data was extracted following PRISMA guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed. Results: We analyzed 57 patients from 10 clinical trials and 3 case reports. The pooled complete and overall response rates were 49.5% (95% CI 0.18-0.81, I2 =65%) and 65.2% (95% CI 0.36-0.91, I2 =57%). The pooled incidence of cytokine release syndrome, immune-effector cell associated neurotoxicity syndrome, and graft-versus-host disease was estimated as 54.4% (95% CI 0.17-0.90, I2 =77%), 3.9% (95% CI 0.00-0.19, I2 =22%), and 1.6% (95%CI 0.00-0.21, I2 =33%), respectively. Conclusion: CAR-T therapy has demonstrated modest efficacy in RR-AML. Major challenges include heterogeneous disease biology, lack of a unique targetable antigen, and immune exhaustion.

Popular Trend of Electronic Cigarettes and Their Adverse Effects on Oral Health.

Electronic cigarettes were originally promoted as a possible tool to assist individuals in quitting smoking, particularly for those who had been tobacco users for an extended period. Compared with traditional tobacco use, these devices were promoted as a safer option. Over the years, it has been proven that conventional cigarettes adversely affect almost all body systems. Owing to the constantly evolving nature of the products and the difficulties in identifying potential e-cigarette effects in traditional tobacco users including combustible and noncombustible forms, studying the impact of e-cigarette usage on oral health is challenging. Although the existing scientific evidence is limited, it indicates that e-cigarette use may have negative effects on oral health. Moreover, the adoption of vaping among young people has increased globally. There is still a lack of awareness regarding the use of e-cigarettes and their associated health complications, especially in developing countries. We aim to sensitize the readers to the pertinent issue, which has clinical and public health significance.

Rate Coefficients for the Gas-Phase Reactions of Nitrate Radicals with a Series of Furan Compounds.

The atmospheric reaction of a series of furan compounds (furan (F), 2-methylfuran (2-MF), 3-methylfuran (3-MF), 2,5-dimethylfuran (2,5-DMF), and 2,3,5-trimethylfuran (2,3,5-TMF)) with nitrate radical (NO3) has been investigated using the relative rate kinetic method in the CHamber for the Atmospheric Reactivity and the Metrology of the Environment (CHARME) simulation chamber at the laboratoire de Physico-Chimie de l'Atmosphere (LPCA) laboratory (Dunkerque, France). The experiments were performed at (294 ± 2) K atmospheric pressure and under dry conditions (relative humidity, RH < 2%) with proton transfer mass reaction-time of flight-mass spectrometer (PTR-ToF-MS) for the chemical analysis. The following rate coefficients (in units cm3 molecule-1 s-1) were determined: furan, k(F) = (1.51 ± 0.38) × 10-12, 2-methylfuran, k(2-MF) = (1.91 ± 0.32) × 10-11, 3-methylfuran, k(3-MF) = (1.49 ± 0.33) × 10-11, 2,5-dimethylfuran, k(2,5-DMF) = (5.82 ± 1.21) × 10-11, and 2,3,5-trimethylfuran, k(2,3,5-TMF) = (1.66 ± 0.69) × 10-10. The uncertainty on the measured rate coefficient (ΔkFC) includes both the uncertainty on the measurement and that on the rate coefficient of the reference molecule. To our knowledge, this work represents the first determination for the rate coefficient of the 2,3,5-TMF reaction with NO3. This work shows that the reaction between furan and methylated furan compounds with nitrate radical (NO3) is the dominant removal pathway during the night with lifetimes between 0.5 and 55 min for the studied molecules.

mTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal Cancer.

The mammalian target of rapamycin (mTOR) is the major controller of a number of important cellular activities, including protein synthesis, cell expansion, multiplication, autophagy, lysosomal function, and cellular metabolism. When mTOR interacts with specific adaptor proteins, it forms two complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The mTOR signaling system regulates gene transcription and protein manufacturing to control proliferation of cell, differentiation of immune cell, and tumor metabolism. Due to its vital role in case of microbial infections, inflammations and cancer development and progression, mTOR has been considered as a key therapeutic target for the development of targeted medication. As autophagy dysfunction is linked to changes in both innate and adaptive immune responses, bacterial clearance defects, and goblet and Paneth cell malfunction, all of these changes are linked to inflammatory bowel diseases (IBD) and colorectal cancer (CRC) pathogenesis. Preclinical and clinical data have shown that the inhibition and induction of autophagy have significant potential to be translated into the clinical applications. In IBD and several CRC models, mTORC1 inhibitors have been found effective. In the recent years, a number of novel mTOR inhibitors have been investigated in clinical trials, and a number of drugs have shown considerably enhanced efficacy when combined with mTOR inhibitors. The future developments in the mTOR targeting medications can benefit patients in individualized therapy. Advanced and innovative medicines that are more effective and have lower drug resistance are still in high demand. New findings could be relevant in medicine development, pharmacological modification, or future mTOR inhibitor research. Therefore, the goal of this review is to present a comprehensive account of current developments on the mTOR pathway and its inhibitors, with an emphasis on the management of microbial infections, the treatment of inflammatory bowel disease, and the management of colon cancer.

In Search of Preferential Macrocyclic Hosts for Sulfur Mustard Sensing and Recognition: A Computational Investigation through the New Composite Method r2SCAN-3c of the Key Factors Influencing the Host-Guest Interactions.

Sulfur mustard (SM) is a harmful warfare agent that poses a serious threat to human health and the environment. Thus, the design of porous materials capable of sensing and/or capturing SM is of utmost importance. In this paper, the interactions of SM and its derivatives with ethylpillar[5]arene (EtP[5]) and the interactions between SM and a variety of host macrocycles were investigated through molecular docking calculations and non-covalent interaction (NCI) analysis. The electronic quantum parameters were computed to assess the chemical sensing properties of the studied hosts toward SM. It was found that dispersion interactions contributed significantly to the overall complexation energy, leading to the stabilization of the investigated systems. DFT energy computations showed that SM was more efficiently complexed with DCMP[5] than the other hosts studied here. Furthermore, the studied macrocyclic containers could be used as host-based chemical sensors or receptors for SM. These findings could motivate experimenters to design efficient sensing and capturing materials for the detection of SM and its derivatives.

Outcomes after venetoclax with hypomethylating agents in myelodysplastic syndromes: a systematic review and meta-analysis.

We present a systematic review and meta-analysis to evaluate outcomes after venetoclax (VEN) with hypomethylating agents (HMA) in myelodysplastic syndromes (MDS). We performed a literature search on PubMed, Cochrane Library, EMBASE, and Clinicaltrials.gov. After screening 2004 manuscripts, 16 studies were included. Data was extracted following PRISMA guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed. We analyzed the outcomes of 373 patients from 11 retrospective studies and five phase 1 b clinical trials. Pooled complete response with or without hematological recovery was 60% (95% CI 0.49-0.7, I2= 67%, n = 373). Hematopoietic cell transplantation was performed in 32% of patients (95% CI 0.2-0.46, I2= 62%, n = 187). Overall mortality was 45% (95% CI 0.31-0.59, I2=54%, n = 140). VEN-HMA combination therapy demonstrated promising outcomes in MDS. Prospective randomized data is needed to ascertain the benefit of VEN and its impact in MDS patients.

Highly Selective Removal of Cationic Dyes from Wastewater by MgO Nanorods.

The organic synthetic dyes employed in industries are carcinogenic and harmful. Dyes must be removed from wastewater to limit or eliminate their presence before dumping into the natural environment. The current study aims to investigate the use of MgO nanoparticles to eliminate basic fuchsine (BF), as a model cationic dye pollutant, from wastewater. The MgO nanorods were synthesized through a coprecipitation method. The obtained nanocomposite was characterized using various techniques such as X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), Brunauer-Emmett-Teller (BET), and FTIR spectroscopy. It was found that the variation of dye concentration and pH influenced the removal of BF by MgO. The adsorption capacity of 493.90 mg/g is achieved under optimum operating conditions (pH = 11, contact time = 236 min, and initial BF concentration = 200 ppm). Pseudo-second-order adsorption kinetics and Freundlich isotherm models best fitted BF sorption onto MgO nanorods. The BF sorption mechanism is associated with the electrostatic attractions and hydrogen bond between the O-H group of MgO and the NH2 groups of BF, as indicated by the pH, isotherms, and FTIR studies. The reusability study indicates that MgO was effectively used to eliminate BF in at least four continuous cycles. The investigation of MgO with different dyes suggests the high adsorption selectivity of BF, crystal violet (CV), and malachite green (MG) dyes compared with methyl orange (MO) dye. Overall, MgO nanorods can act as a potential and promising adsorbent for the efficient and rapid removal of cationic dyes (CV, MG, and BF) from wastewater.

Impact of COVID-19 in hematopoietic stem cell transplant recipients: A systematic review and meta-analysis.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) recipients are at increased risk of mortality and morbidity with coronavirus disease 2019 (COVID-19) due to severe immune dysfunction. METHODS: A literature search was performed on PubMed, Cochrane, and Clinical trials.gov from the date of inception to 12/08/2021. We identified 19 original studies reporting data on COVID-19 in HSCT recipients after screening 292 articles. Data were extracted following preferred reporting items for systematic reviews and meta-analysis guidelines. Quality evaluation was done using the National Institutes of Health (NIH) quality assessment tool. Inter-study variance was calculated using Der Simonian-Laird Estimator. Pooled analysis was conducted using MetaXL. A random-effects model was used to estimate the proportions with 95% confidence intervals (CI). RESULTS: Of 6711 patients in 19 studies, 2031 HSCT patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were analyzed. The median age of patients was 56.9 (range 1-81.6) years, and 63% patients were men according to 14 studies. The median time from transplant to SARS-CoV-2 infection for autologous (auto) and allogeneic (allo) HSCT patients was 23.2 (0.33-350.5) months and 16.4 (0.2-292.7) months, respectively. The median follow-up time after COVID-19 diagnosis was 28 (0-262) days. The COVID-19 mortality rate was 19% (95% CI 0.15-0.24, I2  = 76%, n = 373/2031). The pooled mortality rate was 17% (95% CI 0.12-0.24, I2  = 78%, n = 147/904) in auto-HSCT patients and 21% (95% CI 0.16-0.25, I2  = 60%, n = 231/1103) in allo-HSCT patients. CONCLUSIONS: HSCT recipients have a high risk of mortality and clinical complications due to COVID-19. There is a need for ongoing vigilance, masks, and social distancing, vaccination, and aggressive management of SARS-CoV-2 infection in HSCT recipients.

Detection of subclinical rheumatic heart disease in children using a deep learning algorithm on digital stethoscope: a study protocol.

INTRODUCTION: Rheumatic heart diseases (RHDs) contribute significant morbidity and mortality globally. To reduce the burden of RHD, timely initiation of secondary prophylaxis is important. The objectives of this study are to determine the frequency of subclinical RHD and to train a deep learning (DL) algorithm using waveform data from the digital auscultatory stethoscope (DAS) in predicting subclinical RHD. METHODS AND ANALYSIS: We aim to recruit 1700 children from a group of schools serving the underprivileged over a 12-month period in Karachi (Pakistan). All consenting students within the age of 5-15 years with no underlying congenital heart disease will be eligible for the study. We will gather information regarding sociodemographics, anthropometric data, history of symptoms or diagnosis of rheumatic fever, phonocardiogram (PCG) and electrocardiography (ECG) data obtained from DAS. Handheld echocardiogram will be performed on each study participant to assess the presence of a mitral regurgitation (MR) jet (>1.5 cm), or the presence of aortic regurgitation (AR) in any view. If any of these findings are present, a confirmatory standard echocardiogram using the World Heart Federation (WHF) will be performed to confirm the diagnosis of subclinical RHD. The auscultatory data from digital stethoscope will be used to train the deep neural network for the automatic identification of patients with subclinical RHD. The proposed neural network will be trained in a supervised manner using labels from standard echocardiogram of the participants. Once trained, the neural network will be able to automatically classify the DAS data in one of the three major categories-patient with definite RHD, patient with borderline RHD and normal subject. The significance of the results will be confirmed by standard statistical methods for hypothesis testing. ETHICS AND DISSEMINATION: Ethics approval has been taken from the Aga Khan University, Pakistan. Findings will be disseminated through scientific publications and to collaborators. ARTICLE FOCUS: This study focuses on determining the frequency of subclinical RHD in school-going children in Karachi, Pakistan and developing a DL algorithm to screen for this condition using a digital stethoscope.