To evaluate the diagnostic performance and clinical utility of metagenomic next-generation sequencing (mNGS) in distinguishing immune checkpoint inhibitor-related pneumonitis (CIP) from infectious pneumonia in cancer patients undergoing immunotherapy.

A retrospective tertiary hospital cohort included 34 cancer patients (Feb 2022-Jan 2024) with prior ICI exposure, new/worsening respiratory symptoms, imaging infiltrates, and both mNGS and conventional microbiological testing (CMT). Final diagnoses were adjudicated by a multidisciplinary panel. We compared pathogen detection rates, sensitivity, specificity, and turnaround times (TAT) between mNGS and CMT.

In the infectious pneumonia group, mNGS detected pathogens in 17/18 cases (94%), whereas CMT detected only 6/18 (33%). In the CIP group, mNGS was negative in 14/16 cases (88%), compared with 11/16 negatives by CMT (69%). Using the adjudicated diagnosis as the reference, mNGS showed sensitivity 88%, and specificity 94%. In contrast, CMT's sensitivity was 69%, and specificity 33%. The median TAT for mNGS was 24 hours (IQR 22-31 h), versus 121.5 hours (IQR 80.5-156 h) for CMT (P < 0.001).

mNGS outperforms CMT in both diagnostic accuracy and timeliness for distinguishing CIP from infectious pneumonia among immunotherapy recipients. Incorporation of mNGS into the diagnostic workflow for suspected CIP may improve etiological discrimination and enable timely, individualized treatment. Further large-scale prospective studies are required to confirm these findings.

Background: Asbestos remains a significant global public health issue, with approximately 255,000 deaths attributed to exposure each year, primarily through occupational contact. Mesothelioma rates continue to rise, particularly in areas with a history of industrial exposure. Despite this burden, many countries lack reliable surveillance systems. Colombia has clusters like the one observed in Sibaté, highlighting the urgency of establishing structured, evidence-based surveillance systems. Objective: The aim is to synthesize international experiences to guide the design and implementation of surveillance strategies in Colombia and other low- and middle-income countries facing similar challenges. Methods: Following the JBI methodology for scoping reviews, comprehensive searches were conducted in Medline (PubMed), Embase, the Cochrane Library (OVID), and Google Scholar. Only English-language articles were included, and no time restrictions were applied. Results: Fourteen studies from 11 countries were included, with the majority coming from Italy, followed by Colombia and Brazil. Three main themes emerged: (1) numerous cohort studies reported increased risks of mesothelioma and lung cancer among asbestos-exposed workers, supporting the need for long-term follow-up; (2) structured surveillance systems-such as Italy's ReNaM and Brazil's Datamianto-demonstrated effective models combining data integration, regular medical evaluations, and policy enforcement; (3) considerable variability in surveillance design, target populations, and reporting standards, especially between high-income and resource-limited settings, highlighting the lack of global standardization. Conclusions: Structured, context-specific surveillance programs are essential to identify and manage the health burden of asbestos exposure. International models offer practical frameworks that could be adapted to Colombia's needs. Investing in such systems would strengthen public health responses, improve early detection of asbestos-related diseases (ARDs), and support environmental and occupational justice in affected communities. The included studies do not mention monitoring according to the degree of exposure.

Extrahepatic cholangiocarcinoma is a rare malignant neoplasm characterized by aggressive behavior and poor prognosis. It typically presents in the seventh to eighth decades of life, with a slight male predominance, and most commonly manifests with symptoms related to biliary obstruction; however, atypical clinical presentations may occur. We report the case of a 71-year-old man who presented with acute pancreatitis. Imaging studies failed to identify an underlying neoplasm, and the diagnosis was established only during the autopsy, which revealed a perihilar extrahepatic cholangiocarcinoma involving the proximal extrahepatic bile ducts, with extensive multiorgan infiltration. These findings accounted for the patient's atypical manifestations, including renal dysfunction and gastrointestinal bleeding, which were fully elucidated through postmortem examination. Extrahepatic cholangiocarcinoma represents a diagnostic challenge due to its nonspecific clinical features and its anatomically difficult location for biopsy, particularly when atypical manifestations predominate. This case highlights the value of autopsy in clarifying complex clinicopathologic correlations and provides observations regarding the role of immunohistochemistry in the diagnosis, prognostic assessment, and therapeutic management of these tumors.

To assess global, regional, and national trends in the burden of elderly male breast cancer (EMBC) from 1990 to 2021 and to evaluate projected patterns to 2040.

Estimates were obtained from the Global Burden of Disease 2021 study. Age-standardised incidence, mortality, and disability-adjusted life year rates (ASIR, ASMR, ASDR) were analysed across all countries and Sociodemographic Index (SDI) strata. Long-term changes were quantified using the average annual percent change derived from log-linear models. Joinpoint regression identified temporal inflection points. Age-period-cohort (APC) models characterise independent temporal effects. Mortality changes were decomposed into components attributable to population growth, ageing, and epidemiological change. Inequality was assessed using slope and concentration indexes. Attributable mortality and DALYs were evaluated for alcohol use, dietary risks, and tobacco. Future rates to 2040 were estimated using a Bayesian age-period-cohort (BAPC) model.

Globally, EMBC incidence, mortality, and DALYs increased from 1990 to 2021, with average annual percent changes(AAPC) of 1.8 (95% CI, confidence interval, 1.63 to 1.98), 0.58 (95% CI 0.38 to 0.77), and 0.68 (95% CI 0.43 to 0.92). East Asia recorded the steepest rise in incidence, increasing from 1.65 (95% UI, uncertainty interval, 1.16 to 2.42) to 6.65 per 100000 population (95% UI 2.77 to 9.78). The middle SDI quintile showed the largest increases in all three metrics, rising from 1.62 (95% UI 1.18 to 2.09) to 4.92 per 100000 population (95% UI 2.26 to 6.81). APC analysis indicated pronounced period and cohort effects in middle and low-middle SDI settings. Decomposition identified population growth as the dominant driver of rising burden. Alcohol use and dietary risks accounted for most increases in mortality and DALYs, while tobacco contributed minimally. Cross-country inequality was modest for incidence but more marked for mortality and DALYs. Projections suggest that age-standardised rates will decline gradually by 2040, although absolute case numbers may continue to rise in rapidly ageing regions.

The global burden of EMBC continues to increase, with substantial regional and socioeconomic disparities. Although age-standardised rates are projected to decline, population ageing is expected to sustain or expand absolute numbers of cases and deaths.

prostate cancer is reported in 16.7% of benign prostate hyperplasia (BPH) surgical specimens. This incidental prostate cancer (IPCa) is usually low grade. While incidence rates vary widely across regions, no published data exist from Rwanda, thus motivating this study.

this was a retrospective cross-sectional analysis of Trans-Urethral Resection of Prostate (TURP) and open simple prostatectomy specimens from two tertiary hospitals between January 2015 and October 2022 to identify IPCa rate. The clinical characteristics and pathology reports were retrieved. Independent t-test, Fisher´s exact test, and logistic regression were performed to assess associations between clinical characteristics and occurrence of IPCa.

we included 153 patients, mean age 70 years (SD: ±10). 140/153 patients had Lower Urinary Tract Symptoms (LUTS), macrohematuria 4/153, and low back pain 1/153. IPCa was diagnosed in six individuals (6/153, 4%). One patient (1/6) with hematuria and the sole patient with low back pain had IPCa diagnosis (respectively OR: 16.4, 95% CI: 1.1 - 235.9, P=0.04 and OR 38.8, 95% CI: 1.5 - 881.2, P=0.02). Age, prostate volume, and a PSA >4ng/mL were not predictors of IPCa. Grade group (GG) 2 had 2/6 patients, while GG 1, 3, 4, and 5 had 1/6 each. Clinically, 1/6 were cT1a, 5/6 cT1b, with one patient upstaged to T3b postoperatively. Cancer management was watchful waiting in 2/6, active surveillance in 1/6, and androgen deprivation therapy in 3/6 patients.

the incidence of prostate cancer in BPH specimens may be low but occasionally high-grade. Patients with symptoms beyond LUTS need careful assessment preoperatively. Larger prospective studies are needed to corroborate these findings for clinical use.

Pancreatic cancer (PC) is a highly aggressive malignancy of the digestive system, with an extremely poor prognosis. The mitochondrial unfolded protein response (UPR^mt) can maintain mitochondrial homeostasis and promote tumor progression and chemotherapy resistance. Nevertheless, the functions of UPR^mt-related genes (MRGs) in PC remain undefined.

Gene expression data were obtained from TCGA, GEO, and CPTAC databases. Consensus clustering was performed based on MRGs, with subsequent evaluation of immune infiltration patterns across clusters. Prognostic MRGs were identified using three machine learning algorithms: LASSO regression, Random Survival Forest (RSF), and Extreme Gradient Boosting (XGBoost), combined with Cox regression analysis to establish a MRGs risk score (MRS). Quantitative real-time PCR (qRT-PCR) and western blotting were employed to validate potential mechanisms. Drug sensitivity profiling distinguished therapeutic responses between risk groups. Finally, we developed an MRS-based prognostic nomogram and validated it in multiple cohorts.

PC patients were stratified into two distinct UPR^mt clusters with notable differences in overall survival (OS) and immune cell infiltration. Through screening, we established a novel MRS based on three prognostic core genes (CAT, CEBPB, and PRKN). High MRS patients showed significantly poorer OS compared to low MRS patients. We observed marked differences in drug sensitivity between subgroups and further predicted potential therapeutic agents targeting MRS. The prognostic nomogram based on MRS demonstrated strong predictive accuracy for 1-, 2-, and 3-year OS across both training and validation PC cohorts. Furthermore, western blot analysis preliminarily validated the potential association between UPR^mt and both P53 signaling and glycolysis pathways.

Our study systematically characterizes the prognostic and therapeutic implications of MRGs in PC, establishing a 3-gene MRS capable of reliably predicting OS in PC patients and exploring UPR^mt potential oncogenic mechanisms. These findings provide a valuable reference for individualized therapeutic strategies in PC management.

In a previous study, we found a possible connection between pre-vaccination CD3+CD56+ T cells and seroresponse to influenza vaccination in immunosuppressed patients. Decreased circulating CD3+CD56+ T cells have been described in severe COVID-19, but their role in vaccination is unknown. This study evaluated the humoral immune response after SARS-CoV-2 vaccination in children with cancer following two doses of the BNT162b2 mRNA vaccine. We investigated the relationship between cellular immunity (including CD3+CD56+ T cells) and the post-vaccination antibody response.

A multicenter, prospective cohort study was completed by recruiting patients receiving chemotherapy and healthy controls, who received two doses of the BNT162b2 mRNA vaccine. Flow cytometric analysis of peripheral blood lymphocyte subpopulations was performed before vaccination; serum anti-SARS-CoV-2 IgG was measured before vaccination and 21-28 days after the second vaccination. We evaluated the relationship between various cellular parameters before vaccination and antibody response.

Serological response was assessed in 20 oncology patients and 13 healthy controls. The seroconversion rate was 55% among oncology patients and 92.3% among healthy controls (p = 0.023). Geometric mean fold increase (GMFI) of the titers was 6.69 and 41.64 (p = 0.011), respectively. Flow cytometric analysis revealed a significantly higher seroconversion rate in patients with higher baseline CD3+CD56+ T cell (p = 0.044) and CD56+ NK (p = 0.038) cell counts. Based on GMFI, we found a positive association between a greater antibody response and higher baseline CD4+ (p = 0.007), CD4+CD3+CD56+ (p = 0.019), and CD4+ MAIT (p = 0.010) cell counts, as well as a higher CD4/CD8 ratio (p = 0.029).

Our study suggests that an adequate humoral immune response can be induced by the SARS-CoV-2 mRNA vaccine in pediatric oncology patients. We explored for the first time the possible association between pre-vaccination T lymphocyte subpopulations (CD3+CD56+, CD56+ NK, CD4+, CD4+CD3+CD56+ cells) and the antibody response to the COVID-19 vaccine. We have similar observations as previously reported with influenza vaccination, suggesting that CD3+CD56+ T cells may be involved in the immune response to SARS-CoV-2 vaccines. We highlight the connection between pre-vaccination CD4+ MAIT cell populations and the antibody response.

Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has demonstrated clinical potential in treating relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL); however, enhancing its therapeutic efficacy remains a significant challenge. To this end, bridging therapy with Brutonyg tyrosine kinase inhibitors (BTKi), such as ibrutinib or zanubrutinib, is being investigated as a strategy to improve treatment outcomes.

In this retrospective analysis, we assessed the impact of different durations of BTKi bridging therapy prior to anti-CD19 CAR-T cell infusion in 33 patients with R/R DLBCL. Patients meeting predefined eligibility criteria, including the presence of at least one high-risk prognostic factor. These 33 patients were stratified into two groups based on the duration of BTKi exposure: ≥x months versus <2 months.

The R/R DLBCL patients receiving BTKi for ≥o months demonstrated a higher overall response rate than the patients receiving BTKi for <2 month. There was no statistically significant differences in progression free survival (PFS) or overall survival (OS) between the two groups. Exploratory analyses suggested potential biomarkers for BTKi bridging efficacy, including modulation of nicotinamide phosphoribosyltransferase (NAMPT) and programmed cell death protein 1 (PD-1).

Prolonged BTKi bridging might improve the overall response to CAR-T cell therapy in patients with R/R DLBCL, despite the initial disparities. However, the risk of hematological toxicity associated with extended BTKi use requires attention. Further investigations are essential to validate and translate these observations into clinical practice, thus highlighting the need for further research in this area.

https://www.chictr.org.cn/showproj.aspx?proj=33185, ChiCTR1800019622.

Conventional classification of surgical margins is inadequate for head and neck squamous cell carcinoma (HNSCC) treated with neoadjuvant immunochemotherapy (NICT), as it fails to capture the complex biological changes in the tumor microenvironment. This study aimed to develop a novel definition of a negative margin.

We conducted a retrospective analysis of treatment-naïve, HPV-negative HNSCC patients who completed NICT followed by surgery. Surgical margins underwent multi-modal assessment, including histopathology (tertiary lymphoid structures), tumor burden (Pan-CK, Ki-67), molecular profiling (driver mutations, PD-L1 RNA), and immune contexture (CD8+/FoxP3+ ratio, Granzyme B). A Margin Risk Index (MRIx) was developed by weighting these domains based on their prognostic impact for locoregional control (LRC) and distant metastasis-free survival (DMFS). The MRIx was externally validated in an independent cohort.

The study included a training cohort of 144 patients and an independent validation cohort of 100 patients. The MRIx integrated four domains into a continuous score, stratifying patients into low, intermediate, and high-risk categories. The MRIx significantly outperformed traditional margin assessment, with superior discrimination for both LRC (C-index=0.72) and DMFS (C-index=0.75). External validation confirmed its prognostic power, demonstrating significant risk stratification (log-rank p<0.001 for both LRC and DMFS) and an independent hazard ratio for high-risk patients (HR = 2.95 for LRC; HR = 3.22 for DMFS, both p<0.001).

The proposed MRIx provides a biologically-grounded tool that redefines margin status following NICT. It accurately identifies patients at high risk of recurrence who may benefit from treatment intensification and those with low-risk margins suitable for de-escalation, enabling personalized adjuvant therapy.

Plasma cell leukemia (PCL) is a rare and aggressive hematological malignancy. The long-term prognosis of relapsed/refractory plasma cell leukemia (R/R PCL) remains poor, and few treatment options are available for patients with triple-refractory disease. Chimeric antigen receptor (CAR)-T cell therapy targeting the B-cell maturation antigen (BCMA) has shown promise, though its long-term efficacy and optimal subsequent strategies remain to be fully elucidated.

This retrospective study analyzed the efficacy and safety of BCMA CAR-T therapy in 12 patients with triple-class R/R PCL. Patients were stratified into consolidation (Group 1, allo-HSCT within 3 months post-CAR-T) and non-consolidation (Group 2, no allo-HSCT within 3 months post-CAR-T) groups, with survival outcomes compared between cohorts.

The overall response rate following BCMA-CAR-T cell therapy was 75% (9/12); four patients achieved partial response, four achieved very good partial response, and one patient had complete response. Grade 3-4 cytopenia were universally observed, while 83.3% (10/12)of the patients presented with mild (grade 1-2) cytokine release syndrome. The median progression free survival (PFS) was 8.9 months (95% CI: 4.6, not reached). The 1-year PFS rate was 33.3% (95% CI: 7.8-62.3), and the 2-year PFS rate was 22.2% (95% CI: 3.4-51.3). The median overall survival (OS) was 15.5 months (95% CI: 5.7, not reached). The 1-year OS rate was 55.6% (95% CI: 20.4-80.5), and the 2-year OS rate was 22.2% (95% CI: 3.4-51.3). furthermore, two of the four patients who underwent consolidation therapy showed long-term survival with stringent complete response.

BCMA-CAR-T therapy confers short-term remission and survival benefits in relapsed/refractory plasma cell leukemia (R/R PCL). However, the definitive value of allogeneic hematopoietic stem cell transplantation (allo-HSCT) awaits validation in large-sample prospective studies.