Hematopoietic stem cell transplantation (HSCT) offers curative potential for hematologic malignancies and immune disorders, yet pulmonary complications remain major contributors to non-relapse morbidity and mortality. Traditionally attributed to immune suppression and graft-versus-host disease (GvHD), these complications are increasingly recognized to involve disruption of pulmonary microbial communities. A growing body of clinical and experimental evidence indicates that HSCT-associated perturbations in the lung microbiome, driven by conditioning, antimicrobials, immune injury, and infection, are associated with distinct post-transplant pulmonary phenotypes and, in some cohorts, with mortality risk. Whether these microbial shifts represent causal contributors to lung injury or contextual biomarkers of immune vulnerability remains unresolved, and this distinction carries direct implications for microbiome-targeted intervention. Dysbiotic shifts in the lung have been associated with both infectious and non-infectious complications, including idiopathic pneumonia syndrome, bronchiolitis obliterans syndrome, and fibrotic lung disease. Gut-lung microbial crosstalk may amplify or reflect systemic immune dysfunction, though the directionality of this relationship remains incompletely characterized. Multi-omics approaches, integrating metagenomics, metatranscriptomics, and metabolomics, are beginning to define the host-microbiome interaction signatures that distinguish injury subtypes and predict outcomes. This review synthesizes mechanistic insights into lung microbiome-immune interactions after HSCT, critically appraises the methodological constraints on the current evidence base, and evaluates microbiome-based interventions, including fecal microbiota transplantation, inhaled postbiotics, and precision antimicrobials, as candidate strategies for respiratory protection in transplant recipients, while acknowledging that prospective interventional evidence in this population remains limited.
Antimicrobial management in pediatric transplantation lacks standardized international guidelines, and current practices across European transplant centers remain poorly described. This study aimed to evaluate microbiological screening and peri-transplant antimicrobial strategies among centers participating in the European Reference Network on Transplantation in Children (ERN TransplantChild), including both solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) programs. Between December 2022 and February 2023, healthcare professionals within the network completed a structured survey addressing microbiological screening practices and peri-transplant antimicrobial strategies in pediatric transplant recipients. Of 127 transplant programs invited, 76 (59.8%) responded, including 62 SOT and 14 HSCT programs from 36 centers across 16 European countries. Pre-transplant screening strategies, microbiological methods, and decolonization practices varied substantially between centers. Reported prevalence of methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase-producing organisms was below 10% in most programs. In SOT, perioperative prophylaxis varied according to transplanted organ type. Cephalosporins were most commonly used in kidney and heart transplantation, whereas broader-spectrum regimens, including piperacillin-tazobactam and vancomycin, were more frequently adopted in liver, intestinal, and lung transplantation. Postoperative prophylaxis was continued beyond 24 h in most SOT programs. Antifungal prophylaxis was more commonly adopted in liver, intestinal, and lung transplant recipients. In HSCT, antibacterial peri-transplant use was not routinely prescribed in a substantial proportion of programs, particularly in autologous transplantation, whereas antifungals were widely used in allogeneic HSCT. Marked heterogeneity in microbiological screening and peri-transplant antimicrobial strategies across European pediatric transplant centers underscores the need for transplant-specific, evidence-based guidelines distinguishing between SOT and HSCT settings. These findings provide a foundation for the development of shared clinical pathways and harmonized recommendations.
The aim of this study was to evaluate the efficacy and safety of myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma (R/R T-ALL/LBL), focusing on immune interventions' impact on long-term prognosis. 16 adult patients (≥18 years; 11 male, 5 female; median age 28 years [range 18-50]) with R/R T-ALL/LBL undergoing salvage allo-PBSCT at the Chinese PLA General Hospital between 2013 and 2022 were retrospectively analyzed. All patients were in partial remission (PR) or disease progression (PD) pre-transplant. Primary endpoints were overall survival (OS), progression-free survival (PFS), and relapse rate (RR); secondary endpoints included GVHD incidence and immune intervention efficacy. Median follow-up was 15.5 months (range 2-69). 5 patients (31.3%) survived at last follow-up. At 3-month post-transplantation assessment, 9 patients achieved CR and 5 maintained PR, while 2 patients died of PD within 2 months post-transplant. Among the 14 evaluable patients, CR patients (n = 9) received immunosuppressant tapering without additional intervention: 4 sustained CR, 2 died of relapse, 3 of transplant-related mortality. PR patients (n = 5) underwent initial immunosuppression withdrawal followed by: donor lymphocyte infusions (DLI, n = 3), chemotherapy (n = 1), or DLI + radiotherapy (n = 1). 4 patients ultimately died of relapse, and 1 attained CR. The 1-year OS and PFS were both 56.3%, 1-year RR was 22.1%, and non-relapse mortality rate (NRM) was 27.1%. Myeloablative allo-PBSCT is a feasible salvage therapeutic option for R/R T-ALL/LBL patients. Furthermore, immune interventions, such as DLI, may improve outcomes, particularly in patients with PR.
According to the 2016 World Health Organization classifcation, a germline DEAD-box helicase 41 gene (DDX41) mutation with myeloid neoplasms(MNs) has been newly classifed. Such mutations are clearly linked to late-onset MNs, with patients typically presenting in middle to old age and often manifesting as high-risk AML or MDS. These patients are sensitive to hypomethylating agents, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently recognized as the curative treatment modality. However, pediatric cases of MNs associated with germline DDX41 mutations are extremely rare, resulting in significant gaps in understanding their clinical characteristics, treatment strategies, and prognostic data. This article reports a pediatric patient with high-risk myelodysplastic syndrome (MDS-EB-2) associated with a germline DDX41 mutation (c.316_320del) who underwent unrelated cord blood allogeneic hematopoietic stem cell transplantation. An 8-year-old female patient achieved bone marrow remission with azacitidine and venetoclax and subsequently underwent allogeneic hematopoietic stem cell transplantation from an unrelated umbilical cord blood donor, The conditioning regimen included fludarabine, decitabine, busulfan, and cyclophosphamide, leading to sustained donor engraftment. Post-transplant complications included HHV-6 encephalitis and grade III acute graft-versus-host disease (aGVHD) of the skin and gut, which were managed and controlled. At the 13-month follow-up, the patient remained in complete hematologic remission without recurrence. This case suggests that allo-HSCT is a feasible curative option for children with high-risk MDS and germline DDX41 predisposition, highlighting the critical importance of screening potential donors for the same mutation.
To determine if functional information from gadoxetate disodium-enhanced MRI is useful in assessing prognosis in primary sclerosing cholangitis (PSC). In this retrospective case-controlled study, 73 patients with PSC and gadoxetate-enhanced MRI were enrolled. Four radiologists independently assessed qualitative and quantitative MRI features. The value of these features in predicting adverse events (liver-related death, hepatic decompensation from grade III/IV hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis as well as need for liver transplantation) within 2 years of MRI were compared with recognized radiological scores as well as clinical scoring systems (Mayo Risk Score, Amsterdam-Oxford model and UK PSC score), using multivariate logistic regression and receiver operating characteristic curve analysis. The cohort consisted of 42 males and 31 females, with a mean age of 41.9 years. In the 2-year period after MRI, 26 patients had adverse events, 8 had liver transplantation, and 6 died. On multivariate analysis, only Mayo Risk Score (p = 0.001) and relative enhancement of proximal extrahepatic bile ducts (REPD) (p = 0.035) were significant in predicting adverse outcomes. REPD of < 4.64 had 70% sensitivity and 63% specificity in such an event. The only variable that significantly predicted liver transplantation was ANALI non-gadolinium score (p = 0.0003). ANALI score of > 3 had a sensitivity of 87.5% and specificity of 74.2% for predicting the need for liver transplantation. Relative enhancement ratio of extrahepatic bile ducts at 20 min after gadoxetate disodium provides useful information in predicting adverse events in PSC patients and is complementary or superior to the currently used clinical scoring systems. Question Can functional hepatic and biliary parameters, obtained from gadoxetate-enhanced MRI, be useful in predicting adverse events in patients with primary sclerosing cholangitis? Findings The relative enhancement of proximal bile ducts (REPD) was useful in predicting adverse events and the need for liver transplantation within 2 years of MRI. Clinical relevance ANALI score predicts need for liver transplantation and may be included in MRI reports of patients with PSC. REPD is more difficult to measure on a routine clinical basis and may only be useful in drug trials.
Thrombocytopenia is prevalent in living donor liver transplantation (LDLT), resulting from underlying liver disease and perioperative factors. Although platelet transfusions are frequently required, their response is variable and may be associated with adverse outcomes. This study evaluated the prevalence and severity of thrombocytopenia, platelet transfusion practices, assessed post-transfusion response using corrected count increment (CCI), and predictors of poor CCI in adult LDLT recipients. This prospective observational study was conducted at a quaternary care center after ethical approval. Adult LDLT recipients were enrolled, and clinical, biochemical, intraoperative, and transfusion data were collected. Platelet transfusion response was assessed using CCI post-transfusion; CCI <5,000 was considered a poor response. Among 100 LDLT recipients (median age 52 years; 88% male), preoperative thrombocytopenia was observed in 91% of patients (17% severe). Intraoperative platelet transfusions were administered in 18% of cases. Postoperatively, 66 platelet transfusions were given to 23 patients, with a mean CCI of 9.0 × 10⁹/L. Poor CCI was observed in 10 patients and was associated with higher bilirubin levels, prolonged INR, longer ICU stay, and increased 30-day mortality. Early allograft dysfunction (EAD) at postoperative day 7 was an independent predictor of poor CCI (OR 10.2, 95% CI 2.4-43.1). A platelet count ≤71,000/mm³ on day 7 predicted EAD with 85% sensitivity (AUC 0.79). Thrombocytopenia is highly prevalent in LDLT recipients. Poor CCI is associated with graft dysfunction and adverse outcomes, suggesting that CCI monitoring may help guide transfusion strategies after liver transplantation.
Globally, especially in the Asia Pacific region, chronic hepatitis B infection has led to an undesirable escalating morbidity and mortality with acute-on chronic liver failure, end-staged liver cirrhosis, and hepatocellular carcinoma. This has happened despite the past four decades of major scientific advances made in screening methods, vaccination strategies, highly effective low-cost anti-viral therapies, and surveillance strategies for early detection of hepatocellular carcinoma. To address this health threat, APASL has formed a Viral Elimination Taskforce to unite key opinion leaders from its member countries and regions. The ongoing shifts in hepatitis B epidemiology, socioeconomic changes, and advancements in technology are taken into consideration. With the conjoint efforts of all the members of the APASL Viral Elimination Taskforce, these clinical practice guidelines have been formulated aiming to facilitate healthcare professionals, policy-makers, and patients in making practical and cost-effective management decisions for chronic hepatitis B infection. Altogether, it provides recommendations in 13 major areas related to screening, vaccination, treatment, and HCC surveillance. The implementation of these clinical practice guidelines represents major APASL effort toward elimination of the disease burden due to chronic hepatitis B infection in Asia Pacific region.
Despite promising outcomes in CAR T-cell therapy for relapsed/refractory multiple myeloma (RRMM), nearly all patients eventually relapse. Resistance and relapse may be driven by CAR T-cell and tumor-intrinsic factors. Here, we developed a mechanistic quantitative systems pharmacology (QSP) model of multiple myeloma growth and CAR T-cell therapy using measurable biomarkers to predict and identify factors associated with response and relapse. The model incorporates key components to explore disease dynamics and CAR T-cell expansion. Our model reproduced published pharmacokinetics and biomarker response data from anti-BCMA and anti-GPRC5D CAR T-cell therapies. We then validated the model using clinical biomarker data from a total of 29 real-world RRMM patients treated with commercial anti-BCMA CAR T. Virtual trial simulations, exploring the impact of variable baseline disease and CAR T characteristics on response, predicted that factors associated with worse outcomes are intrinsic to tumor cells (disease burden, low-antigen expression) and CAR T cells (low CAR T-induced killing rate). Interestingly, simulations suggested that a lower baseline percentage of normal plasma cells is associated with higher overall response. The developed model was also used to predict the outcome of BCMA-targeted and GPRC5D-targeted combination CAR T-cell treatment. Sequential combination therapy simulations predicted a better response in scenarios starting with anti-GPRC5D CAR T infusion, followed by anti-BCMA CAR T infusion. Our model can serve as a framework to investigate response mechanisms as well as multi-antigen targeting, and to optimize clinical trial design and dosing regimens.
Patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) frequently suffer severe complications requiring intensive care unit (ICU) admission. While sepsis is a recognized driver of these poor outcomes, its precise impact on short-term mortality in this specific population requires further clarification. We conducted a retrospective cohort study of 65 adult AML patients admitted to the ICU within 100 days post-allo-HSCT at a single tertiary care center. Patients were stratified by the presence of sepsis. Clinical and microbiological data were collected, and univariable Cox proportional hazards regression was used to identify predictors of the primary outcome i.e. 90-day mortality. Sepsis was diagnosed in 70.8 % patients (n=46) and required significantly more organ support, including invasive mechanical ventilation (67.4 % vs 15.8 %; p<0.001) and renal replacement therapy (37.0% vs 5.3%; p=0.009). The presence of sepsis was associated with significantly lower 90-day survival (log-rank p=0.012). In univariable analysis, sepsis was the strongest predictor of 90-day mortality (Hazard Ratio [HR], 3.34; 95% CI, 1.47-7.57; p=0.004). Mechanical ventilation (HR, 3.14; p<0.001) and renal replacement therapy (HR, 2.35; p=0.010) were also 4 significant predictors. The most frequently identified pathogens were Klebsiella species (18.5%), Enterococcus species (13.8%). Vancomycin-resistant Enterococcus (VRE) found in 9.2% patients. Sepsis is a primary and statistically significant driver of 90-day mortality in AML patients admitted to the ICU following allo-HSCT. These findings underscore the urgent need for early sepsis recognition, aggressive management, and robust antimicrobial stewardship in this highly vulnerable population.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) introduced an important public health threat in the world beginning in 2019. The aim of the study was to describe the clinical characteristics, treatment methods and outcomes of pediatric cancer patients and HSCT recipients who developed SARS-CoV-2 infection between 2020 and 2023 in Poland. During the study period among all pediatric oncological patients, 496 children (12.2%), i.e. 204 girls and 292 boys were at least one detected positive during anticancer therapy. Among HSCT recipients at least one episode of SARS-CoV-2 infection was diagnosed in 41 (6.0%; p < 0.001 oncology vs. transplant) patients, i.e. 10 girls, 31 boys including 39 (7.6%) after allo-HSCT and 2 (1.2%) after auto-HSCT (p = 0.001 allo vs. auto). SARS-CoV-2 infection has mild-moderate course in majority of pediatric cancer patients and transplant recipients, however, the presence of severe or critical illness is higher than in the general pediatric population. Interestingly, we observed less severe clinical courses of SARS-CoV-2 infection in the recent year than at the beginning of pandemic.
Ureteral stricture is a rare complication following hematopoietic stem cell transplantation (HSCT). However, its management poses challenges due to the patient's long-term immunosuppression and the limited clinical experience of doctors. This represents the first report of a patient who underwent lingual mucosa graft ureteroplasty (LMGU) for the management of long-segment ureteral stricture following HSCT. Surgical techniques and perioperative management strategies are described. A 25-year-old female with a 10 cm long proximal and middle ureteral stricture following HSCT was successfully treated with robotic-assisted LMGU. The procedure lasted 270 minutes without conversion and intraoperative complications. Intraoperative blood loss was estimated at 50 mL. Postoperative complications included lymphatic fistula (Clavien-Dindo grade Ⅰ) and left upper extremity venous thrombosis (Clavien-Dindo grade Ⅱ). The Double-J stent was removed eight weeks postoperatively. Antegrade urography performed at ten weeks showed an unobstructed urinary tract. During follow-up assessments, the patient reported no symptoms after surgery. The glomerular filtration rate of the left kidney increased from 27.45 mL/min preoperatively to 38.79 mL/min postoperatively. Renal ultrasound performed at 3, 6, 9, and 12 months demonstrated improved hydronephrosis compared to preoperative imaging. Based on the satisfactory outcomes in this case, robotic-assisted LMGU appears to be a safe, minimally invasive, and effective reconstructive technique, providing a promising treatment for select patients with post-HSCT long proximal ureteral strictures.
To evaluate shor t-term outcomes and patient survival among kidney paired donation cases in living donor kidney transplants. The retrospective, observational study was conducted in December 2024 at the Depar tment of Kidney Transplantation Surgery, Pakistan Kidney and Liver Institute and Research Centre, Lahore, Pakistan, and comprised medical records of patients who underwent kidney paired donation living donor transplants from August 3, 2022, to July 9, 2024. Data included demographics, intraoperative and postoperative variables, delayed graft function, length of hospital stay, surgical site infection, rejection rates, graft survival and patient survival at one year. Data was analysed using SPSS 27. Of the 28 subjects in 14 pairs, 20(71.4%) were females and 8(28.6%) were males. The overall mean age was 32.62±14.05 years and the median dialysis duration was 8 months (interquartile range: 10 months). The primary cause of end-stage renal disease among the recipients was unknown in 19(67.9%) cases. Postoperative creatinine levels were stable at 3, 6, 9 and 12 months, and there was only 1(3.6%) graft loss which was owing to acute T-cell-mediated rejection. No cases of delayed graft function and 30-day mortality were noted. Mean length of hospital stay was 6.62±1.50 days. There were 2(7.1%) cases facing complications, including surgical site infection and arterial anastomosis leakage. At 12 months, graft survival rate was 27(96.4%) and patient survival rate was 28(100%). Kidney paired donation in living donor kidney transplants demonstrated favourable short-term outcomes, with high graft survival and low complication rates.
Pediatric liver transplantation has improved long-term survival, but optimal surveillance strategies for late graft injury remain uncertain. This systematic review evaluated the utility of protocol liver biopsies for detecting subclinical histopathological abnormalities after pediatric liver transplantation, particularly fibrosis, inflammation, steatosis, and rejection. We conducted a PRISMA-compliant systematic review of PubMed and ScienceDirect, with supplementary hand-searching of references and trial registries. Eligible studies included English-language primary studies of pediatric liver transplant recipients undergoing surveillance liver biopsy. Two reviewers independently screened studies, extracted data, and assessed methodological quality using the Newcastle-Ottawa Scale. Fifteen studies comprising 2004 pediatric liver transplant recipients were included. Protocol biopsies frequently identified histological abnormalities despite minimal or absent clinical symptoms. Fibrosis was common and appeared to increase over time, with crude estimates suggesting any fibrosis in approximately 66.2% of patients at 1 year and 81.6% at 15 years post-transplant. Inflammation was also prevalent but tended to decline over time. Several factors were inconsistently associated with fibrosis and inflammation, including donor gender, graft type, immunosuppression regimen, donor-specific antibodies, and surgical complications. In comparative data, protocol biopsies detected more subclinical rejection than for-cause biopsies in stable recipients. In selected cases, repeat protocol or targeted follow-up biopsies after treatment modification may help determine whether inflammation or fibrosis is stabilizing, improving, or progressing. Protocol liver biopsies are a valuable surveillance tool in pediatric liver transplant follow-up, enabling early detection of clinically silent graft pathology and potentially informing timely immunosuppression adjustment.
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Sarcoidosis is a multifactorial granulomatous disease that affects adults of all ages, primarily targeting the lungs. Symptoms can range from none at all to severe respiratory failure requiring lung transplantation. Diagnosis is made using three main criteria: compatible clinical or radiological findings, histological proof of non-necrotizing granulomatous inflammation in tissue, and ruling out other causes of granulomatous disease. Pulmonary fibrosis, advanced findings on high-resolution chest CT, decreased pulmonary function, and pulmonary hypertension are widely recognized as significant predictors of adverse clinical outcomes. A narrative, non-systematic review of important recent literature was carried out using computerized database searches, manual searches, and authoritative sources. This review examines the various patterns observed in high-resolution computerized tomography of the chest and their association with the severity and the pathophysiology of sarcoidosis. The patterns addressed include nodules, ground-glass opacities, consolidations, honeycombing, traction bronchiectasis, and cysts. Both historical and current methods of categorizing high-resolution CT interstitial findings will be reviewed. · Chest HRCT in sarcoidosis demonstrates a broad spectrum of interstitial lung disease patterns, including micronodules, ground-glass opacities, traction bronchiectasis, honeycombing, and cystic change, with important implications for differential diagnosis.. · The diagnosis of pulmonary sarcoidosis requires concordant clinical and radiologic findings, histologic evidence of non-necrotizing granulomatous inflammation, and exclusion of alternative granulomatous disorders.. · Fibrotic HRCT manifestations of sarcoidosis are associated with adverse clinical outcomes, including impaired pulmonary function, pulmonary hypertension, and chronic respiratory failure, and should be distinguished from UIP/IPF despite overlapping imaging features.. · Al-Qaqaa R, Lazarus MS, Franco A. Spectrum of Interstitial Lung Disease in Sarcoidosis. Rofo 2026; DOI 10.1055/a-2871-9924. Die Sarkoidose ist eine multifaktorielle granulomatöse Erkrankung, die Erwachsene jeden Alters betrifft und hauptsächlich die Lunge befällt. Die Symptome reichen von völlig symptomfrei bis hin zu schwerem Lungenversagen, das eine Lungentransplantation erforderlich macht. Die Diagnose wird anhand von drei Hauptkriterien gestellt: entsprechende klinische oder radiologische Befunde, histologischer Nachweis einer nicht-nekrotisierenden granulomatösen Entzündung im Gewebe sowie der Ausschluss anderer Ursachen für eine granulomatöse Erkrankung. Lungenfibrose, eindeutige Befunde in der hochauflösenden Thorax-Computertomografie (CT), verminderte Lungenfunktion und pulmonale Hypertonie gelten allgemein als signifikante Prädiktoren für einen ungünstigen klinischen Verlauf. Eine narrative, nicht-systematische Übersichtsarbeit über wichtige aktuelle Literatur wurde mithilfe computergestützter Datenbankrecherchen, manueller Suchen und fundierter Quellen erstellt. Diese Übersicht untersucht die verschiedenen Muster, die in der hochauflösenden Thorax-CT beobachtet werden, sowie deren Zusammenhang mit dem Schweregrad und der Pathophysiologie der Sarkoidose. Zu den untersuchten Mustern gehören Knötchen, milchglasartige Trübungen, Konsolidierungen, Wabenbildung, Traktionsbronchiektasien und Zysten. Sowohl historische als auch aktuelle Methoden zur Kategorisierung interstitieller Befunde in der hochauflösenden CT werden untersucht. · Die hochauflösende Thorax-CT bei Sarkoidose zeigt ein breites Spektrum an interstitiellen Lungenerkrankungsmustern, darunter Mikroknoten, milchglasartige Trübungen, Traktionsbronchiektasien, Wabenbildung und zystische Veränderungen, mit wichtigen Implikationen für die Differentialdiagnose.. · Die Diagnose einer pulmonalen Sarkoidose erfordert übereinstimmende klinische und radiologische Befunde, den histologischen Nachweis einer nicht-nekrotisierenden granulomatösen Entzündung sowie den Ausschluss von anderen granulomatösen Erkrankungen.. · Fibrotische Manifestationen in der hochauflösenden Thorax-CT bei Sarkoidose sind mit einem ungünstigen klinischen Outcome verbunden, darunter eingeschränkte Lungenfunktion, pulmonale Hypertonie und chronisches Lungenversagen, und sollten trotz sich überlappender bildgebender Merkmale von einer gewöhnlichen interstitiellen Pneumonie/idiopathischen Lungenfibrose abgegrenzt werden..
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Colorectal cancer (CRC) remains among the most prevalent and deadliest malignancies worldwide, with limited survival outcomes, particularly in patients with metastatic disease. Despite advances in immunotherapy, immune checkpoint inhibitors (ICIs) have shown efficacy mainly in mismatch repair-deficient (dMMR) CRC, while responses in mismatch repair-proficient (pMMR) microsatellite-stable (MSS) cases remain limited. Emerging evidence highlights the gut microbiome as a critical factor influencing CRC development, progression, and therapeutic response. In particular, the gut microbiota has been shown to affect the efficacy of ICIs, with dysbiosis contributing to treatment resistance and specific microbial taxa enhancing antitumor immune responses. Preclinical and clinical studies have demonstrated that microbiome-based interventions, including probiotics, fecal microbiota transplantation (FMT), dietary modulation, and traditional medicines, can restore immune function by modulating immune cell populations and producing immunoregulatory metabolites. These effects may enhance responsiveness to ICIs and contribute to the suppression of tumor growth. However, we also address key limitations in this field, including inconsistent findings and safety concerns, such as infection risks, to guide future translational efforts. Overall, while microbiome-based interventions represent a promising adjunct to CRC immunotherapy, rigorous clinical trials and mechanistic validation are required before their routine clinical implementation.
Artificial stone-associated silicosis (AS silicosis) has emerged over the past decade as a severe, rapidly progressive, and preventable occupational lung disease affecting workers who manufacture, fabricate, and install artificial stone countertops. Characterized by short latency, accelerated progression, and high morbidity and mortality, AS silicosis disproportionately affects young workers employed in precarious conditions. In response to the growing global burden of disease, this American Thoracic Society workshop was convened in 2025 to review the current state of knowledge regarding AS silicosis, synthesize the current evidence, and identify priorities for research, clinical care, public health surveillance, and prevention. Workshop participants reviewed data spanning exposure science, epidemiology, clinical manifestations, health equity, and policy responses. Evidence demonstrates that artificial stone (AS) dust is highly toxic, containing high concentrations of respirable crystalline silica, resin-derived volatile compounds, and trace metals, resulting in exposures that routinely exceed occupational exposure limits. Despite widespread implementation of wet methods, ventilation, and respiratory protection, hazardous exposures persist across diverse settings globally, highlighting fundamental limitations of existing control strategies. Clinically, AS silicosis is associated with high rates of progressive massive fibrosis, autoimmune disease, infection, respiratory failure, and increasing need for lung transplantation. Treatment options remain limited, underscoring the importance of early detection and exposure cessation. The workshop identified critical gaps in medical screening and public health surveillance worldwide, with inconsistent regulatory frameworks, low compliance, underreporting, and delayed diagnoses. Case detection is often dependent on symptomatic presentation rather than proactive screening, exacerbating disease severity and inequities in care. International experiences illustrate both the consequences of regulatory inaction and the potential impact of decisive interventions, including Australia's prohibition of crystalline silica-containing artificial stone. This report concludes that AS silicosis represents a failure of primary prevention and calls for coordinated global action. Key priorities include strengthening surveillance systems, ensuring equitable access to screening and care, developing effective therapeutics, advancing exposure science, and implementing higher-order preventive strategies, including the elimination or substitution of high-silica AS. Without urgent and sustained intervention, these products will continue to impose devastating and avoidable harm on workers worldwide.
Acute myocardial infarction (AMI) is one of the main causes of global morbidity and mortality. Stem cell-based therapy offers a promising approach for myocardial regeneration and tissue repair. Among them, bone marrow-derived stem cells (BMSCs) have shown remarkable therapeutic benefits in various clinical scenarios. Therefore, this study aimed to systematically evaluate the efficacy and safety of BMSCs in patients with AMI. The computer retrieved the Cochrane Library, PubMed, Web of Science and Wiley Online Library databases, collected the randomized controlled trials on BMSCs for the treatment of AMI published in October 2025, and conducted data analysis using RevMan 5.4 and Stata 18.0. We enrolled 25 trials with 1822 patients, 960 patients in the BMSCs group, and 862 patients in the conventional treatment group. Meta-analysis findings indicated that BMSCs transplantation significantly enhanced left ventricular ejection fraction (LVEF) of patients with AMI relative to controls (MD = 2.45, 95% CI: 1.39 to 3.51) and reduced wall motion score index (WMSI) (SMD = -0.32, 95% CI: -0.49 to -0.15). For left ventricular end-diastolic volume (LVEDV) (SMD = -0.01, 95% CI: -0.16 to 0.13), left ventricular end-systolic volume (LVESV) (SMD = -0.04, 95% CI: -0.13 to 0.06) and myocardial infarct size (SMD = 0.01, 95% CI: -0.14 to 0.15), there was a trend toward improvement after infusion of BMSCs, but the difference was not statistically significant. In terms of safety, BMSCs transplantation did not increase the risk of major adverse cardiovascular events (MACEs) (OR = 0.80, 95% CI: 0.57 to 1.12). BMSCs can effectively improve cardiac function in patients with AMI and demonstrate a favorable safety profile. However, their effect on ventricular remodeling remains uncertain, warranting further high-quality evidence to assess long-term outcomes. CRD420251147871.
Extracorporeal membrane oxygenation (ECMO) has become an essential supportive therapy for patients with severe respiratory and/or cardiac failure. While conventional configurations such as veno-venous and veno-arterial ECMO have well-established roles, they are limited by important physiological trade-offs, particularly in patients with concomitant right ventricular dysfunction. Venopulmonary ECMO (VP ECMO) has emerged as a distinct and increasingly utilized configuration designed to provide right ventricular unloading while preserving physiologic pulmonary circulation and enabling extracorporeal gas exchange. By draining venous blood and returning it directly to the pulmonary artery, VP ECMO bypasses the failing right ventricle, reduces venous congestion, improves pulmonary hemodynamics, and supports gas exchange without the systemic complications associated with veno-arterial-ECMO. This review summarizes the physiological principles underlying VP ECMO, outlines cannulation strategies and configurations, and discusses clinical indications with an emphasis on patient phenotyping. Particular attention is given to its role in acute right ventricular failure, acute respiratory distress syndrome with right ventricular dysfunction, postleft ventricular assist device right heart failure, and as a bridge to lung transplantation. Emerging clinical evidence suggests that VP ECMO may improve hemodynamic stability, facilitate early mobilization, and enhance survival in carefully selected patients. However, data remain largely limited to observational studies and case series. Further prospective studies are required to refine patient selection, optimize timing, and define standardized management strategies for VP ECMO.