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Infants who are exclusively breastfed in the first six months of age receive adequate nutrients, achieving optimal immune protection and growth. In addition to the known nutritional components of human breast milk (HBM), i.e., water, carbohydrates, fats and proteins, it is also a rich source of microRNAs, which impact epigenetic mechanisms. This comprehensive work presents an up-to-date overview of the immunomodulatory constituents of HBM, highlighting its content of circulating microRNAs. The epigenetic effects of HBM are discussed, especially those regulated by miRNAs. HBM contains more than 1400 microRNAs. The majority of these microRNAs originate from the lactating gland and are based on the remodeling of cells in the gland during breastfeeding. These miRNAs can affect epigenetic patterns by several mechanisms, including DNA methylation, histone modifications and RNA regulation, which could ultimately result in alterations in gene expressions. Therefore, the unique microRNA profile of HBM, including exosomal microRNAs, is implicated in the regulation of the genes responsible for a variety of immunological and physiological functions, such as FTO, INS, IGF1, NRF2, GLUT1 and FOXP3 genes. Hence, studying the HBM miRNA composition is important for improving the nutritional approaches for pregnancy and infant’s early life and preventing diseases that could occur in the future. Interestingly, the composition of miRNAs in HBM is affected by multiple factors, including diet, environmental and genetic factors.

Rationale: Allogeneic hematopoietic stem-cell transplantation (Allo-HSCT) recipients are still believed to be poor candidates for ICU management. Methods: We investigated outcomes and determinants of mortality in a large multicenter retrospective cohort of Allo-HSCT patients admitted between January 1, 2015, and December 31, 2020, to 14 French ICUs. The primary endpoint was 90-day mortality. Measurements and Main Results: In total, 1,164 patients were admitted throughout the study period. At the time of ICU admission, 765 (66%) patients presented with multiple organ dysfunction, including acute respiratory failure in 40% ( n  = 461). The median sepsis-related organ failure assessment score was 6 (interquartile range, 4-8). Invasive mechanical ventilation, renal replacement therapy, and vasopressors were required in 438 (38%), 221 (19%), and 468 (41%) patients, respectively. ICU mortality was 26% (302 deaths). Ninety-day, 1-year, and 3-year mortality rates were 48%, 63%, and 70%, respectively. By multivariable analysis, age > 56 years (odds ratio [OR], 2.0 [95% confidence interval (CI), 1.53-2.60]; P  < 0.001), time from Allo-HSCT to ICU admission between 30 and 90 days (OR, 1.68 [95% CI, 1.17-2.40]; P  = 0.005), corticosteroid-refractory acute graft-versus-host disease (OR, 1.63 [95% CI, 1.38-1.93]; P  < 0.001), need for vasopressors (OR, 1.9 [95% CI, 1.42-2.55]; P  < 0.001), and mechanical ventilation (OR, 3.1 [95% CI, 2.29-4.18]; P  < 0.001) were independently associated with 90-day mortality. In patients requiring mechanical ventilation, mortality rates ranged from 39% (no other risk factors for mortality) to 100% (four associated risk factors for mortality). Conclusions: Most critically ill Allo-HSCT recipients survive their ICU stays, including those requiring mechanical ventilation, with an overall 90-day survival rate reaching 51.8%. A careful assessment of goals of care is required in patients with two or more risk factors for mortality.

Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: B. G. reports receipt of nonfinancial support from Gilead Sciences, MSD, and Pfizer outside the submitted work. F. R. reports receipt of personal fees from AbbVie, AstraZeneca, Gilead Sciences, Janssen, Merck, Roche, and ViiV Healthcare outside the submitted work. E. C. reports personal fees from GILEAD, SANOFI-GENZYME, and BAXTER outside the submitted work. B. T. reports receipt of nonfinancial support from Gilead Sciences and personal fees from AbbVie, Gilead Sciences, Lilly Oncology, and Incyte outside the submitted work. None declared (R. Lécuyer, N. I., F. C., R. Lavergne, F. G., F. M., D. B., A. C., M. G., Y. C., A. N.).

Background: The impact of induction type or high-risk viral discordance on older kidney transplant recipients is unclear. Herein, we analyzed the association between induction type, viral discordance, and outcomes for older recipients., Methods: We analyzed the Scientific Registry of Transplant Recipients standard analysis file for all primary kidney transplant recipients older than 55 y who were transplanted between 2005 and 2022. All transplants were crossmatch negative and ABO-compatible. Recipients were discharged on tacrolimus and mycophenolate ± steroids. Recipients were categorized into 3 groups by induction received: rabbit antithymocyte globulin (r-ATG; N = 51 079), interleukin-2 receptor antagonist (IL-2RA; N = 22 752), and alemtuzumab (N = 13 465). Kaplan-Meier curves were generated for recipient and graft survival, and follow-up was censored at 10 y. Mixed-effect Cox proportional hazard models examined the association between induction type, high-risk viral discordance, and outcomes of interest. Models were adjusted for pertinent recipient and donor characteristics., Results: Induction type did not predict recipient survival in the multivariable model, whereas Epstein-Barr virus high-risk discordance predicted 14% higher mortality (1.14 [1.07-1.21], P  < 0.01). In the multivariable model for death-censored graft survival, alemtuzumab, but not IL-2RA, was associated with an increased risk of graft loss (1.18 [1.06-1.29], P  < 0.01) compared with r-ATG. High-risk cytomegalovirus discordance predicted 10% lower death-censored graft survival (1.10 [1.01-1.19], P  < 0.02). Live donor and preemptive transplantation were favorable predictors of survival., Conclusions: In this large cohort of older transplant recipients, alemtuzumab, but not IL-2RA, induction was associated with an increased risk of graft loss compared with r-ATG. Cytomegalovirus and Epstein-Barr virus high-risk viral discordance portended poor graft and recipient survival, respectively., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Local surgical excision of T1 rectal adenocarcinoma is a well-established approach. Yet, there are still open questions regarding the recurrence rates and its risk factors. Methods: A retrospective multicenter study including all patients who underwent local excision of early rectal cancer with an open or MIS approach and had a T1 lesion from 2010 to 2020 in six academic centers. Data included demographics, preoperative studies, surgical findings, postoperative outcomes, and local and systemic recurrence. A univariable and multivariable logistic regression analysis was performed to identify risk factors for recurrence. Results: Overall, 274 patients underwent local excision of rectal lesions. Of them, 97 (35.4%) patients with a T1 lesion were included in the cohort. The mean age was 69 ± 10.5 years, and 42 (43.3%) were female. The mean distance of the lesions from the anal verge was 7.8 ± 3.2 cm, and the average tumor size was 2.7 ± 1.6 cm. Eighty-two patients (85%) had a full-thickness resection. Eight patients (8%) had postoperative complications. Kikuchi classification of submucosal (SM) involvement was reported in 29 (30%) patients. Twelve patients had SM1, two SM2, and fifteen SM3. Following pathology, 24 patients (24.7%) returned for additional surgery or treatment. The overall recurrence rate was 14.4% (14 patients), with 11 patients having a local recurrence and 6 having a systemic metastatic recurrence, 3 of which had both. The mean time for recurrence was 2.78 ± 2.8 years and the overall mortality rate was 11%. On univariable and multivariable logistic regression analysis of recurrence vs. non-recurrence groups, the strongest and most significant association and possible risk factors for recurrence were larger lesions (4.3 vs. 2.5 cm, p < 0.001) with an OR of 6.67 (CI-1.82-24.36), especially for tumors larger than 3.5 cm, mucinous histology (14.3% vs. 1.2%, p = 0.004, OR of 14.02, CI-1.13-173.85), and involved margins (41.7% vs. 16.2%, p = 0.003, OR of 9.59, CI-2.14-43.07). The open transanal excision (TAE) approach was also identified as a possible significant risk factor in univariant analysis, while SM3 level penetration showed only a trend. Conclusion: Surgical local excision of T1 rectal malignancy is a safe and viable option. Still, one in four patients received additional treatment. There is an almost 15% chance for recurrence, especially in large tumors, mucinous histology, or involved margin cases. These high-risk patients might warrant additional intervention and stricter surveillance protocols.

Background: Cytomegalovirus (CMV) infection in patients with cellular immune deficiencies is associated with significant morbidity and mortality. However, data on CMV end-organ disease (CMV-EOD) in critically ill, immunocompromised patients are scarce. Our objective here was to describe the clinical characteristics and outcomes of CMV-EOD in this population., Methods: We conducted a multicenter, international, retrospective, observational study in adults who had CMV-EOD and were admitted to any of 18 intensive care units (ICUs) in France, Israel, and Spain in January 2010-December 2021. Patients with AIDS were excluded. We collected the clinical characteristics and outcomes of each patient. Survivors and non-survivors were compared, and multivariate analysis was performed to identify risk factors for hospital mortality., Results: We studied 185 patients, including 80 (43.2%) with hematologic malignancies, 55 (29.7%) with solid organ transplantation, 31 (16.8%) on immunosuppressants, 16 (8.6%) with solid malignancies, and 3 (1.6%) with primary immunodeficiencies. The most common CMV-EOD was pneumonia (n = 115, [62.2%] including 55 [47.8%] with a respiratory co-pathogen), followed by CMV gastrointestinal disease (n = 64 [34.6%]). More than one organ was involved in 16 (8.8%) patients. Histopathological evidence was obtained for 10/115 (8.7%) patients with pneumonia and 43/64 (67.2%) with GI disease. Other opportunistic infections were diagnosed in 69 (37.3%) patients. Hospital mortality was 61.4% overall and was significantly higher in the group with hematologic malignancies (75% vs. 51%, P = 0.001). Factors independently associated with higher hospital mortality were hematologic malignancy with active graft-versus-host disease (OR 5.02; 95% CI 1.15-27.30), CMV pneumonia (OR 2.57; 95% CI 1.13-6.03), lymphocytes < 0.30 × 10 9 /L at diagnosis of CMV-EOD (OR 2.40; 95% CI 1.05-5.69), worse SOFA score at ICU admission (OR 1.18; 95% CI 1.04-1.35), and older age (OR 1.04; 95% CI 1.01-1.07)., Conclusions: Mortality was high in critically ill, immunocompromised patients with CMV-EOD and varied considerably with the cause of immunodeficiency and organ involved by CMV. Three of the four independent risk factors identified here are also known to be associated with higher mortality in the absence of CMV-EOD. CMV pneumonia was rarely proven by histopathology and was the most severe CMV-EOD., (© 2024. The Author(s).)

Immune checkpoint inhibitors (ICIs) present clinicians with the challenge of managing immune-related adverse events (irAEs), which can range from mild to severe due to immune system activation 1 . While guidelines recommend discontinuing ICIs for grade 3 partial and all grade 4 irAEs, there is growing interest in rechallenging patients based on oncological outcomes, particularly for cardiovascular and neurological irAEs where data remains scarce 1,2 . We retrospectively evaluated the safety of ICI rechallenge following grade 3-4 irAEs, specifically focusing on cardiovascular and neurological events, in patients discussed at our multidisciplinary immunotoxicity assessment board between 2019 and 2021. Fifteen patients were included, with a median time to severe irAE onset of 49 days. Among them, five patients experienced neurological adverse events (NAEs): aseptic meningitis (3), inflammatory polyradiculoneuropathy (1), and ophthalmoplegia (1), while one patient presented with myocarditis. Of the 15 patients retreated with ICIs after initial severe irAEs, 11 (73%) remained free of subsequent irAEs, two (13%) experienced recurrence of the initial irAE, and two (13%) developed new irAEs distinct from the initial event. The median time to event recurrence was 69 days, occurring no earlier than the initial severe irAE. In the subset analysis focusing on severe cardiovascular and neurological irAEs, rechallenge with ICIs was generally well tolerated. However, one patient treated with anti-PD1 experienced a relapse of grade 2 aseptic meningitis. Overall, our findings suggest that rechallenging with ICIs after severe irAEs, including those affecting the cardiovascular and neurological systems, may be safe, particularly after irAE regression and corticosteroid withdrawal., Competing Interests: EG: congress fees and investigator for BMS and MSD. RV: speakers’ bureau for BMS. SM-P: consultant on boards for BMS. AP-L: congress fees for BMS. CDu: Clinical investigation in trials, congress fees and member of boards for BMS, MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Eldani, Kostine, Faure, Lazaro, Rigothier, Hiriart, Teulières, Poullenot, Haissaguerre, Zysman, Veillon, Vergnenegre, Issa, Domblides, Mary-Prey, Beylot-Barry, Pham-Ledard, Dutriaux, Sole, Duval and Gerard.)

Background: Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI-myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this "cardiomyotoxicity" are lacking., Methods: A multicenter registry collected data retrospectively from 17 countries between 2014-2023. A multivariable cox regression model (hazard-ratio(HR), [ 95% confidence-interval]) was used to determine risk factors for the primary composite outcome: severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardio-muscular symptoms, diagnostics, and treatments. Time-dependent covariates were used and missing data were imputed. A point-based prognostic risk score was derived and externally validated., Results: In 748 patients (67% male, age 23-94), 30-days incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17% respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (HR=3.60[1.93-6.72]), presence of cardio-muscular symptoms (HR=2.60 [1.58-4.28]), low QRS-voltage on presenting electrocardiogram (HR for ≤0.5mV versus >1mV=2.08[1.31-3.30]), left ventricular ejection fraction (LVEF) <50% (HR=1.78[1.22-2.60]), and incremental troponin elevation (HR=1.86 [1.44-2.39], 2.99[1.91-4.65], 4.80[2.54-9.08], for 20, 200 and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-days primary outcome incidence increased gradually from 3.9%(risk-score=0) to 81.3%(risk-score≥4). This risk-score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low risk patients who were managed with no immunosuppression resulting in no cardio-myotoxic events., Conclusions: ICI-myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low-QRS voltage, depressed LVEF, and cardio-muscular symptoms. A risk-score incorporating these features performed well., Trial Registration Number: NCT04294771 and NCT05454527.

Objective: To investigate the incidence rate of primary brain tumors (PBTs) among Palestinian children over a 6-year interval. This study also aimed to identify the predominant histopathologic types identified in these children., Methods: This retrospective epidemiologic study focused on PBTs in children (<15 years) in Palestine. The data were collected from the registry system at Al-Makassed Hospital in Jerusalem, a prominent referral institution in Palestine and the largest center for PBTs in the region, over a 6 years period from 2018 to 2023., Results: The incidence rate of PBTs in children (<15 years) was 1.33 per 100,000 person-years, with a 5% mortality rate. Pilocytic astrocytoma was the most common type (24%), followed by medulloblastoma (15.2%) and glioblastoma (6.3%). About one half of the tumors in children were malignant. Headaches were the most common first sign or symptom. About 20% of brain tumors in children were situated within the ventricles, making it the most prevalent location of these tumors, followed by the cerebellum (15.19%) and frontal lobe (11.39%)., Conclusions: This is the first national study in Palestine investigating PBTs in children. The crude incidence rate of primary brain tumors among Palestinian children was lower than the incidence rate in many countries around the world. It is recommended that more research be done on the epidemiology and distribution of PBTs in children in Palestine., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical presentation, severity, and mortality of PcP has not been adequately evaluated., Research Question: Does the underlying disease and immunosuppression causing PcP impact the outcome and clinical presentation of the disease?, Study Design and Methods: In this multicenter retrospective observational study, conducted from January 2011 to December 2021, all consecutive patients admitted with a proven or probable diagnosis of PcP according to the European Organisation for Research and Treatment of Cancer consensus definitions were included to assess the epidemiology and impact of underlying immunosuppressive diseases on overall and 90-day mortality., Results: Overall, 481 patients were included in the study; 180 (37.4%) were defined as proven PcP and 301 (62.6%) were defined as probable PcP. Patients with immune-mediated inflammatory diseases (IMIDs) or solid tumors had a statistically poorer prognosis than other patients with PcP at day 90. In multivariate analysis, among the HIV-negative population, solid tumor underlying disease (OR, 5.47; 95% CI, 2.16-14.1; P < .001), IMIDs (OR, 2.19; 95% CI, 1.05-4.60; P = .037), long-term corticosteroid exposure (OR, 2.07; 95% CI, 1.03-4.31; P = .045), cysts in sputum/BAL smears (OR, 1.92; 95% CI, 1.02-3.62; P = .043), and SOFA score at admission (OR, 1.58; 95% CI, 1.39-1.82; P < .001) were independently associated with 90-day mortality. Prior corticotherapy was the only immunosuppressant associated with 90-day mortality (OR, 1.67; 95% CI, 1.03-2.71; P = .035), especially for a prednisone daily dose ≥ 10 mg (OR, 1.80; 95% CI, 1.14-2.85; P = .010)., Interpretation: Among patients who were HIV-negative, long-term corticosteroid prior to PcP diagnosis was independently associated with increased 90-day mortality, specifically in patients with IMIDs. These results highlight both the needs for PcP prophylaxis in patients with IMIDs and to early consider PcP curative treatment in severe pneumonia among patients with IMIDs., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: B. G. reports receipt of nonfinancial support from Gilead Sciences, MSD, and Pfizer, outside the submitted work. F. R. reports receipt of personal fees from Abbvie, Astra Zeneca, Gilead Sciences, Janssen, Merck, Roche, and ViiV Healthcare, outside the submitted work. E. C. reports personal fees from Gilead, Sanofi-Genzyme, and Baxter, outside the submitted work. None declared (R. L., N. I., F. C., R.-a. L., F. G., F. M., D. B., A. C., M. G., Y. C., A. N., B. T.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Backgrounds: Primary brain tumors (PBTs) are uncommon, but they significantly increase the risk of disability and death. There is a deficiency of data concerning the epidemiology and anatomical distribution of PBTs among adults in Palestine., Methods: A retrospective descriptive study in which data were collected from the clinical reports of Palestinian patients diagnosed with PBTs at Al-Makassed Hospital during the period (2018-2023)., Results: In Palestinian adolescents and adults, the incidence rate of PBTs was 3.92 per 100,000 person-years. Glioblastoma (18.8%) was the most common type identified, and it was more common in males. Non-malignant tumors were more common than malignant tumors (2.41 vs. 1.52 per 100,000). The mortality rate from PBTs was 4.8%. The most common initial symptom was headaches, and it occurred more with non-malignant tumors (57.28% vs. 42.72%, p-value < 0.001). Cerebral meninges (26.3%) were the most common location for primary brain tumors (p-value < 0.001)., Conclusion: This is the first study of primary brain tumor epidemiology in Palestine. The overall incidence of PBTs in Palestinian adolescents and adults was 3.96 per 100,000, which was lower than the incidence rate of primary brain tumors worldwide. More studies on the epidemiology and distribution of PBTs in Palestine are recommended., (© 2024. The Author(s).)

This study aims to assess the safety, virological, and clinical outcomes of convalescent plasma transfusion (CPT) in immunocompromised patients hospitalized for coronavirus disease 2019 (COVID-19). We conducted a retrospective multicenter cohort study that included all immunosuppressed patients with COVID-19 and RNAemia from May 2020 to March 2023 treated with CPT. We included 81 patients with hematological malignancies (HM), transplants, or autoimmune diseases (69% treated with anti-CD20). Sixty patients (74%) were vaccinated, and 14 had pre-CPT serology >264 BAU/mL. The median delay between symptom onset and CPT was 23 days [13-31]. At D7 post-CPT, plasma PCR was negative in 43/64 patients (67.2%), and serology became positive in 25/30 patients (82%). Post-CPT positive serology was associated with RNAemia negativity (p < 0.001). The overall mortality rate at D28 was 26%, being higher in patients with non-B-cell HM (62%) than with B-cell HM (25%) or with no HM (11%) (p = 0.02). Patients receiving anti-CD20 without chemotherapy had the lowest mortality rate (8%). Positive RNAemia at D7 was associated with mortality at D28 in univariate analysis (HR: 3.05 [1.14-8.19]). Eight patients had adverse events, two of which were severe but transient. Our findings suggest that CPT can abolish RNAemia and ameliorate the clinical course in immunocompromised patients with COVID-19., (© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Central catheter-related bloodstream infections (CRBIs) can lead to severe complications, including suppurative thrombophlebitis, endocarditis, and metastatic infections. While complications due to CRBIs caused by Staphylococcus aureus (SA) are well-known, there are limited data regarding CRBIs caused by other bacteria., Methods: This 2-year retrospective single-center study of patients with CRBIs from a tertiary care hospital examined the hematogenous complications associated with CRBIs according to patient characteristics, central venous catheter (CVC) types, and causative bacteria., Results: All in all, 254 patients with confirmed CRBIs were included; 285 bacteria types were isolated, mainly Enterobacteriaceae (n = 94), coagulase-negative Staphylococci (CNS, n = 82), SA (n = 45), and non-fermenting Gram-negative bacteria (NGB, n = 45). Among the patients, 35 developed at least one hematogenous complication (14 %), including suppurative thrombophlebitis (n = 15), endocarditis (n = 7) and metastatic infections (n = 16). In multivariate analysis, hemodialysis, persistent bacteremia for at least 3 days, and CRBIs caused by SA were associated with increased risk for hematogenous complications, while previous curative anticoagulant treatment was associated with reduced risk. Diabetes, CVC maintenance, and hematogenous complications were associated with increased 3-month mortality., Conclusion: A thorough investigation of hematogenous complications should be envisioned in patients with persistent bacteremia, particularly those with SA infections and those on hemodialysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Goals and Background: Gluten-free diet (GFD) includes a higher intake of sugars and fats. Previous studies have investigated its effect on body mass index (BMI) in celiac disease (CD) patients but had contradictive conclusions. Thus, we conducted a systematic review and meta-analysis examining the effect of GFD on BMI in CD patients., Study: Systematically, we conducted literature research using Medline, Scopus, and Embase, and we identified 1565 potential studies/abstracts. Only studies of patients with CD under a GFD with recorded BMI before and after dietary intervention were included. Subgroup analyses based on study design and BMI categories were performed. We calculated the pooled odds ratios (ORs) and 95% confidence intervals (Cls) for the number of patients in each BMI group according to the World Health Organization (WHO) definitions after GFD using fixed and random effect meta-analysis., Results: The analysis included 10 studies and 38 sub-studies/data sets, which encompassed 2450 patients from 5 countries. We found nonsignificant odds for changing the BMI group (pooled OR 0.972, 95% CI: 0.858-1.101, P=0.65) after GFD. However, looking specifically at BMI subgroups, we found higher odds for BMI category change after GFD in underweight patients (OR 0.588, 95% CI: 0.479-0.723, P <0.001), and overweight patients,25

Background : Local excision by transanal endoscopic microsurgery (TEM) is considered an acceptable treatment for rectal adenomas with high-grade dysplasia (HGD). This study aims to assess the likelihood of harboring an invasive carcinoma in preoperatively diagnosed HGD polyps and evaluate the risk factors for tumor recurrence in patients with final HGD pathology. Methods : Data from patients who underwent TEM procedures for adenomatous lesions with HGD from 2005 to 2018 at the Rabin Medical Center, Hasharon Hospital, were analyzed. Collected data included patient demographics, preoperative workup, tumor characteristics and postoperative results. Follow-up data including recurrence assessment and further treatments were reviewed. The analysis included two subsets: preoperative pathology of HGD (sub-group 1) and postoperative final pathology of HGD (sub-group 2) patients. Results : Forty-five patients were included in the study. Thirty-six patients had a preoperative diagnosis of HGD, with thirteen (36%) showing postoperative invasive carcinoma. Thirty-two patients had a final pathology of HGD, and three (9.4%) experienced tumor recurrence. Large tumor size (>5 cm) was significantly associated with recurrence ( p = 0.03). Conclusions : HGD rectal polyps are associated with a significant risk of invasive cancer. Tumor size was a significant factor in predicting tumor recurrence in patients with postoperative HGD pathology. The TEM procedure is an effective first-line treatment for such lesions.

Importance: Traumatic injury is a leading cause of hospitalization among people experiencing homelessness. However, hospital course among this population is unknown., Objective: To evaluate whether homelessness was associated with increased morbidity and length of stay (LOS) after hospitalization for traumatic injury and whether associations between homelessness and LOS were moderated by age and/or Injury Severity Score (ISS)., Design, Setting, and Participants: This retrospective cohort study of the American College of Surgeons Trauma Quality Programs (TQP) included patients 18 years or older who were hospitalized after an injury and discharged alive from 787 hospitals in North America from January 1, 2017, to December 31, 2018. People experiencing homelessness were propensity matched to housed patients for hospital, sex, insurance type, comorbidity, injury mechanism type, injury body region, and Glasgow Coma Scale score. Data were analyzed from February 1, 2022, to May 31, 2023., Exposures: People experiencing homelessness were identified using the TQP's alternate home residence variable., Main Outcomes and Measures: Morbidity, hemorrhage control surgery, and intensive care unit (ICU) admission were assessed. Associations between homelessness and LOS (in days) were tested with hierarchical multivariable negative bionomial regression. Moderation effects of age and ISS on the association between homelessness and LOS were evaluated with interaction terms., Results: Of 1 441 982 patients (mean [SD] age, 55.1 [21.1] years; (822 491 [57.0%] men, 619 337 [43.0%] women, and 154 [0.01%] missing), 9065 (0.6%) were people experiencing homelessness. Unmatched people experiencing homelessness demonstrated higher rates of morbidity (221 [2.4%] vs 25 134 [1.8%]; P < .001), hemorrhage control surgery (289 [3.2%] vs 20 331 [1.4%]; P < .001), and ICU admission (2353 [26.0%] vs 307 714 [21.5%]; P < .001) compared with housed patients. The matched cohort comprised 8665 pairs at 378 hospitals. Differences in rates of morbidity, hemorrhage control surgery, and ICU admission between people experiencing homelessness and matched housed patients were not statistically significant. The median unadjusted LOS was 5 (IQR, 3-10) days among people experiencing homelessness and 4 (IQR, 2-8) days among matched housed patients (P < .001). People experiencing homelessness experienced a 22.1% longer adjusted LOS (incident rate ratio [IRR], 1.22 [95% CI, 1.19-1.25]). The greatest increase in adjusted LOS was observed among people experiencing homelessness who were 65 years or older (IRR, 1.42 [95% CI, 1.32-1.54]). People experiencing homelessness with minor injury (ISS, 1-8) had the greatest relative increase in adjusted LOS (IRR, 1.30 [95% CI, 1.25-1.35]) compared with people experiencing homelessness with severe injury (ISS ≥16; IRR, 1.14 [95% CI, 1.09-1.20])., Conclusions and Relevance: The findings of this cohort study suggest that challenges in providing safe discharge to people experiencing homelessness after injury may lead to prolonged LOS. These findings underscore the need to reduce disparities in trauma outcomes and improve hospital resource use among people experiencing homelessness.

We studied 50 patients with invasive nocardiosis treated during 2004-2023 in intensive care centers in France and Belgium. Most (65%) died in the intensive care unit or in the year after admission. Nocardia infections should be included in the differential diagnoses for patients in the intensive care setting.

Invasive fusariosis can be life-threatening, especially in immunocompromised patients who require intensive care unit (ICU) admission. We conducted a multicenter retrospective study to describe clinical and biologic characteristics, patient outcomes, and factors associated with death and response to antifungal therapy. We identified 55 patients with invasive fusariosis from 16 ICUs in France during 2002----2020. The mortality rate was high (56%). Fusariosis-related pneumonia occurred in 76% of patients, often leading to acute respiratory failure. Factors associated with death included elevated sequential organ failure assessment score at ICU admission or history of allogeneic hematopoietic stem cell transplantation or hematologic malignancies. Neither voriconazole treatment nor disseminated fusariosis were strongly associated with response to therapy. Invasive fusariosis can lead to multiorgan failure and is associated with high mortality rates in ICUs. Clinicians should closely monitor ICU patients with a history of hematologic malignancies or stem cell transplantation because of higher risk for death.

To estimate the diagnostic performance of Mucorales polymerase chain reaction (PCR) in Bronchoalveolar lavage fluid (BALF) in routine practice. This was a single-center retrospective study including all consecutive patients >18 years who underwent Mucorales PCR assay in BALF between January 2021 and May 2022. Index testing was prospectively performed using the MycoGENIE Aspergillus spp.-Mucorales spp. PCR. The reference was the diagnosis of pulmonary mucormycosis by the Adjudication Committee. Mucorales PCR in BALF was performed for 938 patients and was positive for 21 of 938 (2.2%). Eleven pulmonary mucormycosis (including one disseminated) were diagnosed. Among them, one (9.1%) was classified as proven mucormycosis, three (27.3%) as probable, and seven (63.6%) as possible according to the EORTC/MSGERC 2019 criteria. The main host factor was hematological malignancy (10 of 11, 90.9%). Mucorales PCR was positive in serum for eight patients (72.7%). Three patients had positive PCR in BALF, but negative in serum. The mean cycle threshold value was significantly lower in mucormycosis than false-positive cases. Sensitivity was 72.7% (95% confidence interval [CI], 43.4-90.3%), and specificity was 98.6% (95% CI, 97.6-99.2%). The positive and negative predictive values were 38.1% (95% CI, 20.8-59.1%) and 99.7% (95% CI, 99.1-99.9%), respectively. Mucorales PCR in BALF showed good diagnostic performance for mucormycosis, particularly in combination with serum PCR. A positive result should be interpreted with caution, given the possibility of carriage in the airway. However, its high negative predictive value and specificity suggest the utility of Mucorales PCR in BALF in the diagnosis of pulmonary mucormycosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Trans-anal endoscopic microsurgery (TEM) enables a good visualization of the surgical field and is considered the method of choice for excision of adenomas and early T1 rectal cancer. The rectum and retro-rectal space might be the origin of uncommon neoplasms, benign and aggressive, certain require radical trans-abdominal surgery, while others can be treated by a less aggressive approach. In this study we report outcomes in patients undergoing TEM for rare and non-adenomatous rectal and retro-rectal lesions over a period of 11 years., Aim: To report outcomes in patients undergoing TEM for rare and non-adenomatous rectal and retro-rectal lesions over a period of 11 years., Methods: Between January 2008 to December 2019 a retrospective analysis was completed for all patients who underwent TEM for non-adenomatous rectal lesion or retro-rectal mass in our institution. Patients were discharged once diet was well tolerated and no complications were identified. They were evaluated at 3 wk post operatively, then at 3-mo intervals for the first 2 years and every 6 mo depending on the nature of the final pathology. Clinical examination and rectoscopy were performed during each of the follow-up visits., Results: Out of 198 patients who underwent TEM during the study period, 18 had non-adenomatous rectal or retro-rectal lesions. Mean age was 47 years. The mean size of the lesions was 2.9 mm, with a mean distance from the anal margin of 7.9 cm. Mean surgical time was 97.8 min. There were no intra-operative neither late post-operative complications. Mean length of stay was 2.5 d. Mean patient follow-up duration was 42 mo., Conclusion: TEM allows for reduced morbidity given its minimally invasive nature. Surgeons should be familiar with the technique but careful patient selection should be considered. It can be used safely for uncommon rectal and selected retro-rectal lesions without compromising outcomes. We believe that it should be reasonably considered as one of the surgical methods when treating rare lesions., Competing Interests: Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Infective endocarditis (IE) is increasingly affecting older patients. However, data on their management are sparse, and the benefits of surgery in this population are unclear., Methods: We included patients with left-sided IE (LSIE) aged ≥ 80 years enrolled in a prospective endocarditis cohort managed in Aquitaine, France, from 2013 to 2020. Geriatric data were collected retrospectively to identify factors associated with the 1-year risk of death using Cox regression., Results: We included 163 patients with LSIE (median age, 84 years; men, 59%; rate of prosthetic LSIE, 45%). Of the 105 (64%) patients with potential surgical indications, 38 (36%) underwent valve surgery: they were younger, more likely to be men with aortic involvement, and had a lower Charlson comorbidity index. Moreover, they had better functional status at admission (ie, the ability to walk unassisted and a higher median activities of daily living [ADL] score; n = 5/6 vs 3/6, P = .01). The 1-year mortality rate in LSIE patients without surgical indications was 28%; it was lower in those who were operated on compared with those who were not despite a surgical indication (16% vs 66%, P < .001). Impaired functional status at admission was strongly associated with mortality regardless of surgical status. In patients unable to walk unassisted or with an ADL score <4, there was no significant surgical benefit for 1-year mortality., Conclusions: Surgery improves the prognosis of older patients with LSIE and good functional status. Surgical futility should be discussed in patients with altered autonomy. The endocarditis team should include a geriatric specialist., Competing Interests: Potential conflicts of interest . F. B. reports research grants from Gilead and ViiV Healthcare and payments for educational events from Gilead, ViiV Healthcare, and MSD. The remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The most common technique for treating benign and early malignant rectal lesions is transanal endoscopic microsurgery (TEM). Local excision is an acceptable technique for high-risk and elderly patients, but there are hardly any data regarding young patients., Aim: To describe TEM outcomes in patients under 50 years of age., Methods: We collected demographic, clinical, and pathological data from all patients under the age of 50 years who underwent the TEM procedure at Hasharon Rabin Medical Center from January 2005 to December 2018., Results: During the study period, a total of 26 patients under the age of 50 years underwent TEM procedures. Their mean age was 43.3 years. Eleven (42.0%) were male. The mean operative time was 67 min, and the mean tumor size was 2.39 cm, with a mean anal verge distance of 8.50 cm. No major intraoperative or postoperative complications were recorded. The median length of stay was 2 d. Seven (26.9%) lesions were adenomas with low-grade dysplasia, four (15.4%) were high-grade dysplasia adenomas, two were T1 carcinomas (7.8%), and three were T2 carcinomas (11.5%). No residual disease was found following endoscopic polypectomy in two patients (7.8%), but four (15.4%) had other pathologies. Surgical margins were negative in all cases. Local recurrence was detected in one patient 33 mo following surgery., Conclusion: Among young adult patients, TEM for benign rectal lesions has excellent outcomes. It may also offer a balance between the efficacy of complete oncologic resection and postoperative quality of life in the treatment of rectal cancer. In some cases, it may be considered an alternative to radical surgery., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest or financial ties to disclose., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The association between long-term omeprazole use and gastric cancer (GC) risk is controversial. The aim of this study was to investigate the incidence of GC in elderly community-dwelling omeprazole chronic users with/without aspirin compared to non-users., Methods: The registry of a large health management organization was searched for all community-dwelling members aged ≥65 years from January 2002 to December 2016. Data on demographics, background parameters, and chronic omeprazole and aspirin use (>11 prescriptions/year) were retrieved. Those diagnosed with new-onset GC during the study period (from January 2003) were identified., Results: Of 51 405 subjects who met the inclusion criteria, 197 were diagnosed with GC during a mean follow-up period of 8.74 ± 4.16 years. This group accounted for 0.7% of PPI chronic users (72/11 008) and 0.3% (125/40 397) of nonusers (P < 0.001). GC risk was directly associated with omeprazole chronic use [hazard ratio (HR) 2.03, 95% confidence interval (CI): 1.51-2.73, P < 0.001] and inversely associated with aspirin chronic use (HR 0.55, 95% CI: 0.40-0.75, P < 0.001). Each year of omeprazole use increased GC risk by 9%, and each year of aspirin use decreased GC risk by 10% among omeprazole chronic users. The lowest rate of GC was found in omeprazole nonusers/ aspirin chronic users, and the highest, in omeprazole chronic users/aspirin nonusers., Conclusion: Higher GC rate was associated with omeprazole chronic use and inversely associated with aspirin chronic use relative to omeprazole nonuse in community-dwelling elderly., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Both AIDS-defining and non-AIDS-defining cancers (ADC/NADC) predispose people living with HIV (PLHIV) to critical illnesses. The objective of this multicentre study was to investigate the prognostic impact of ADC and NADC in PLHIV admitted to the intensive care unit (ICU)., Methods: All PLHIV admitted over the 2015-2020 period in 12 university-affiliated ICUs in France were included in the study cohort. The effect of ADC and NADC on in-hospital mortality (primary study endpoint) was measured through logistic regression with augmented backward elimination of potential independent variables. The association between ADC/NADC and treatment limitation decision (TLD) during the ICU stay (secondary study endpoint) was analysed. One-year mortality in patients discharged alive from the index hospital admission (exploratory study endpoint) was compared between those with ADC, NADC or no cancer., Results: Amongst the 939 included PLHIV (median age, 52 [43-59] years; combination antiretroviral therapy, 74.4%), 97 (10.3%) and 106 (11.3%) presented with an active NADC (mostly lung and intestinal neoplasms) and an active ADC (predominantly AIDS-defining non-Hodgkin lymphoma), respectively. Inaugural admissions were common. Bacterial sepsis and non-infectious neoplasm-related complications accounted for most of admissions in these subgroups. Hospital mortality was 12.4% in patients without cancer, 30.2% in ADC patients and 45.4% in NADC patients (P < 0.0001). NADC (adjusted odds ratio [aOR], 7.00; 95% confidence interval [CI], 4.07-12.05) and ADC (aOR, 3.11; 95% CI 1.76-5.51) were independently associated with in-hospital death after adjustment on severity and frailty markers. The prevalence of TLD was 8.0% in patients without cancer, 17.9% in ADC patients and 33.0% in NADC patients (P < 0.0001)-organ failures and non-neoplastic comorbidities were less often considered in patients with cancer. One-year mortality in survivors of the index hospital admission was 7.8% in patients without cancer, 17.0% in ADC patients and 33.3% in NADC patients (P < 0.0001)., Conclusions: NADC and ADC are equally prevalent, stand as a leading argument for TLD, and strongly predict in-hospital death in the current population of PLHIV requiring ICU admission., (© 2023. La Société de Réanimation de Langue Francaise = The French Society of Intensive Care (SRLF).)

Cryotherapy has recently been examined as a potential treatment for alopecia areata (AA). AA is classically managed with intralesional or systemic steroids but relapse rates among those with longstanding disease are high. This narrative review serves to describe the existing studies evaluating cryotherapy for the treatment of AA and examine studies comparing cryotherapy with intralesional steroid injection for the treatment of AA. A review of the literature from 1990 to 2022 was conducted looking for keywords such as &ldquo;alopecia areata&rdquo; and &ldquo;cryotherapy". A total of 8 studies were identified. Three studies assessed the efficacy of liquid nitrogen cryotherapy for the treatment of AA and found approximately 60% of patients responded to treatment and achieved hair regrowth. Three studies compared cryotherapy with intralesional corticosteroid injection, and 2 studies compared cryotherapy with topical corticosteroid therapy. There was no statistically significant difference in efficacy, but there is some evidence to suggest that relapse rates were lower in the cryotherapy group. Treatment protocols differed between studies regarding the number of cycles used for cryotherapy, dosage of intralesional steroids, and patient populations used. Some studies examined cases of recalcitrant AA while other studies examined all cases of AA. More research with larger sample sizes and with similar experimental procedures is necessary to assess the clinical efficacy of cryotherapy.Kaiser M, Issa N, Yaghi M, et al. Review of superficial cryotherapy for the treatment of alopecia areata. J Drugs Dermatol. 2023;22(8):802-809. doi:10.36849/JDD.7431.

Introduction: In most cases of parathyroid adenoma (PA), it is not palpable and physical examination shows no remarkable findings. Hence diagnosis requires an index of suspicion. The current paper describes four cases of severe hypercalcemia secondary to PA., Presentation of Cases: Case 1 - 29 years old Sudanese female with history of nausea/vomiting, fatigue, loss of appetite and bone aches. She had large palpable left lower neck swelling, and high calcium and PTH. Ultrasound (US) neck and SPECT/CT scan after sestamibi injection showed left inferior PA. Case 2-73 years old Sudanese male referred with history of abdominal pain and flatulence. He had severely high calcium, elevated parathormone (PTH), and high 24-hour urine calcium. US and SPECT/CT showed a left inferior PA. Case 3-54 years old Bangladeshi male, referred with history of renal colic/urolithiasis. Laboratory results showed severely high calcium and PTH levels. US and SPECT/CT scan showed right inferior PA. Case 4-35 years old Tunisian female, 12 weeks pregnant, referred with recurrent nausea and vomiting of increasing frequency from the second week of pregnancy. Laboratory tests revealed severe hypercalcemia and high PTH. US showed two parathyroid lesions., Discussion: The patients were admitted as emergency cases and investigations diagnosed severe hypercalcemia secondary to PA. All patients underwent neck exploration and PA excision. Histology confirmed PA. The four cases were swiftly assessed and treated before progressing into the more serious hypercalcemic crisis which can lead to grave consequences, particularly in the case of the pregnant female. All patients recovered with no complications and were clinically well with normal calcium level on follow up., Conclusion: Severe hypercalcemia must be swiftly and thoroughly assessed to prevent the more serious hypercalcemic crisis. Clinicians need to be suspicious of parathyroid adenoma as a probable cause. Severe hypercalcemia is often accompanied with vomiting, and in pregnant females, this could be mistaken for hyperemesis gravidarum. Excision of the parathyroid adenoma treats the condition and follow up of serum calcium and PTH confirms the favorable outcome of surgery., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Androgenetic alopecia (AGA) is the most common cause of alopecia in males and females. Minoxidil and finasteride are the only FDA-approved treatments for AGA. New treatments including Platelet Rich Plasma (PRP) and microneedling have shown promising results. The purpose of this literature review was to highlight recent studies examining the effects of topical minoxidil combined with PRP to minoxidil or PRP monotherapy. The method used for this paper includes a systematic review of the literature from 2010 to 2022 using the PubMed, EMBASE, and MEDLINE databases examining studies evaluating combination therapies for AGA. Three randomized control trials compared combination PRP + topical 5% minoxidil to either no treatment, 5% minoxidil, or PRP only. Two studies found increased hair growth at five months and at six months following combined therapy. Another study found an increase in hair density and improved patient satisfaction with combination therapy compared to monotherapy. A prospective study revealed that patients treated with combined 5% minoxidil, PRP, and microneedling reported the highest patient and physician satisfaction compared to minoxidil monotherapy. An observational study evaluating topical 5% minoxidil with PRP reported an increase in hair diameter after one year of combination treatment compared to minoxidil monotherapy. PRP therapy combined with minoxidil and microneedling in a retrospective study was shown to increase hair growth compared to PRP with minoxidil as well as PRP or minoxidil monotherapy. In conclusion, a variety of studies demonstrated superior treatment response with a combination of PRP and minoxidil therapy in patients with AGA. Limitations to this study include different PRP preparation protocols, few randomized control studies, and small sample sizes., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Cutaneous and Aesthetic Surgery.)

Background: Ultrasound-guided percutaneous liver biopsy (UPLB) is currently performed mainly to determine if new hepatic space occupying lesions (SOL) represent benign, primary malignant, or metastatic disease. This study sought to investigate the outcome of UPLB in this setting., Methods: In a retrospective study, patients with a new hepatic SOL who underwent UPLB during 1/2006-12/2016 were included and followed to 12/2018. Clinical data and pathology reports were reviewed. Mortality within 60 days and no change in patients' management following UPLB were defined as medically futile., Results: Included 140 patients, 50% male, mean age 68.8 ± 11.5 years; 112 patients died, all of malignant disease. 32 patients (23%) died within 60 days of UPLB. Median post-UPLB survival was 151 days. Survival was significantly shorter in patients with >1 hepatic lesion (n = 108) or an extrahepatic malignant lesion (n = 77) (p = 0.0082, p = 0.0301, respectively). On Cox Proportional Hazards analysis, significant predictors of mortality within 60 days of UPLB were: age as a continuous variable, (HR 1.070, 95% CI 1.011-1.131, p = 0.018), serum albumin <2.9 g/dL, (HR 4.822 95% CI 1.335-17.425, p = 0.016) and serum LDH >1500 U/L (HR 9.443, 95% CI 3.404-26.197, p < 0.0001)., Conclusions: In patients with these features or with disseminated disease, liver biopsy should be carefully reconsidered., Competing Interests: Declaration of competing interest The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Calcific aortic stenosis (CAS) is more prevalent, occurs earlier, progresses faster and has worse outcomes in patients with chronic kidney disease (CKD). The uremic toxin indoxyl sulfate (IS) is powerful predictor of cardiovascular mortality in these patients and a strong promoter of ectopic calcification whose role in CAS remains poorly studied. The objective of this study was to evaluate whether IS influences the mineralization of primary human valvular interstitial cells (hVICs) from the aortic valve., Methods: Primary hVICs were exposed to increasing concentrations of IS in osteogenic medium (OM). The hVICs' osteogenic transition was monitored by qRT-PCRs for BMP2 and RUNX2 mRNA. Cell mineralization was assayed using the o-cresolphthalein complexone method. Inflammation was assessed by monitoring NF-κB activation using Western blots as well as IL-1β, IL-6 and TNF-α secretion by ELISAs. Small interfering RNA (siRNA) approaches enabled us to determine which signaling pathways were involved., Results: Indoxyl-sulfate increased OM-induced hVICs osteogenic transition and calcification in a concentration-dependent manner. This effect was blocked by silencing the receptor for IS (the aryl hydrocarbon receptor, AhR). Exposure to IS promoted p65 phosphorylation, the blockade of which inhibited IS-induced mineralization. Exposure to IS promoted IL-6 secretion by hVICs, a phenomenon blocked by silencing AhR or p65. Incubation with an anti-IL-6 antibody neutralized IS's pro-calcific effects., Conclusion: IS promotes hVIC mineralization through AhR-dependent activation of the NF-κB pathway and the subsequent release of IL-6. Further research should seek to determine whether targeting inflammatory pathways can reduce the onset and progression of CKD-related CAS., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Transforming growth factor β (TGF-β) is an important signaling molecule which is expressed in three different isoforms in mammals (i.e. TGF-β1, -β2, and -β3). The interaction between TGF-β and its receptor triggers several pathways, which are classified into SMAD-dependent (canonical) and SMAD-independent (non-canonical) signaling, whose activation/transduction is finely regulated by several mechanisms. TGF-β is involved in many physiological and pathological processes, assuming a dualistic role in cancer progression depending on tumor stage. Indeed, TGF-β inhibits cell proliferation in early-stage tumor cells, while it promotes cancer progression and invasion in advanced tumors, where high levels of TGF-β have been reported in both tumor and stromal cells. In particular, TGF-β signaling has been found to be strongly activated in cancers after treatment with chemotherapeutic agents and radiotherapy, resulting in the onset of drug resistance conditions. In this review we provide an up-to-date description of several mechanisms involved in TGF-β-mediated drug resistance, and we report different strategies that are currently under development in order to target TGF-β pathway and increase tumor sensitivity to therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)