Annals of medicine最新文献

Background: Acute myeloid leukaemia (AML) is a highly heterogeneous haematologic malignancy. Current therapeutic strategies include chemotherapy, targeted therapy and haematopoietic cell transplantation (allo-HSCT) and autologous haematopoietic cell transplantation (auto-HSCT). The graft-versus-leukaemia (GVL) effect and graft-versus-host disease (GVHD) in allo-HSCT remain major research foci, with emerging evidence highlighting the synergistic roles of T cells and natural killer (NK) cells in allo-HSCT immunity. This review systematically integrates the cooperative immunological interactions between T cells and NK cells and elucidates their critical significance in post-transplant immunotherapy.

Methods: This review systematically summarizes the cytotoxic mechanisms, immune reconstitution processes and related immunotherapeutic approaches involving T cells and NK cells in AML in the context of allo-HSCT and further elucidates their unique role in post-transplant immune regulation from the perspective of coordinated T-cell and NK-cell interactions.

Results: T cells and NK cells exert synergistic effects in post-transplant immune reconstitution, GVL responses, GVHD regulation and subsequent immunotherapeutic interventions. Early NK-cell reconstitution provides a critical window for the restoration of T-cell function, whereas cytokines derived from T cells, such as IL-2 and IL-15, further enhance NK-cell activity. This dynamic immunological interplay not only shapes the balance between GVL and GVHD, but also informs the development of post-transplant immunotherapeutic strategies.

Conclusion: The dynamic interplay between T cells and NK cells plays a pivotal role in allo-HSCT for AML. This review systematically integrates the cooperative functions of T cells and NK cells within the allo-HSCT immune landscape, offering new perspectives for advancing post-transplant immunotherapy. A deeper understanding of these mechanisms is expected to provide a theoretical foundation for optimizing post-transplant immune interventions in AML patients and for developing more precise therapeutic strategies.

Background and purpose: The benefit of adding anti-PD-1 antibodies to definitive chemoradiotherapy (dCRT) in elderly patients with esophageal squamous cell carcinoma (ESCC) remains uncertain. This study evaluated its efficacy and safety versus dCRT alone.

Materials and methods: We retrospectively analyzed the patients aged ≥ 70 years with ESCC treated at three academic centers from 2009 to 2023. All patients received first-line dCRT and the study group additionally received anti-PD-1 antibodies (IO group). Propensity score matching (PSM) was applied to balance baseline factors.

Results: A total of 241 patients were enrolled, including 130 in the IO group and 111 in the dCRT group. After 1:1 PSM (110 patients per group), no significant differences in overall survival (OS) or progression-free survival (PFS) were observed. The median OS was 34.5 vs 33.7 months (HR = 0.86, 95%CI: 0.58-1.28, p = 0.467) and median PFS was 29.8 vs 17.8 months (HR = 0.79, 95%CI: 0.55-1.13, p = 0.194). Multivariate Cox analysis identified high nutritional risk as an independent predictor of worse OS (p = 0.014), while both advanced TNM stage (p = 0.030) and high nutritional risk (p = 0.016) were independently associated with shorter PFS. Subgroup analyses suggested that patients with good performance, better nutritional status or lower comorbidity burden may benefit from combination therapy. Grade 3-4 adverse events were comparable between two groups.

Conclusion: Adding anti-PD-1 antibodies to dCRT did not result in a significant improvement in OS or PFS in the ESCC patients aged ≥ 70 years; however exploratory findings indicate a potential PFS signal in selected patients with favorable baseline conditions, which requires confirmation in prospective studies.

Background: Postural Orthostatic Tachycardia Syndrome (POTS) and Neurally-Mediated Hypotension (NMH) are heterogeneous syndromes characterized by dysautonomia and multisystem symptoms. Mast cell activation, often manifesting as hives, has been proposed as a contributing mechanism, but its prevalence and clinical relevance in POTS and NMH are poorly defined.

Method: Patients from the Johns Hopkins POTS Clinic completed surveys assessing hives frequency and symptom burden using the Malmö POTS, the Composite Autonomic Symptom Score (COMPASS)-31, and a pain questionnaire. Associations between hives and clinical features were evaluated among patients with confirmed POTS, NMH, or clinically diagnosed orthostatic intolerance.

Result: Among 188 respondents, 80 (42.6%) reported hives sometimes and 33 (17.6%) reported hives often or always. Increasing hives frequency was associated with higher Malmö POTS scores and greater autonomic symptom burden across multiple COMPASS-31 subdomains, including gastrointestinal, bladder, and vasomotor symptoms (all p < 0.05). Hives was also associated with pain (OR 3.47, 95% CI 1.54-7.77, p = 0.002) and tingling (OR 5.73, CI 2.15-15.26, p < 0.001), but not orthostatic symptoms. These associations persisted after multivariable adjustment.

Conclusion: Hives are common in orthostatic intolerance syndromes and are associated with increased symptom burden. Future studies are needed to clarify the role of mast cell activation and evaluate mast cell-targeted therapies.

Background and objective: Chlamydia psittaci and Legionella pneumophila are common atypical pathogens that cause severe community-acquired pneumonia (CAP). This study aimed to compare the clinical features and outcomes of Chlamydia psittaci pneumonia (CPP) and Legionella pneumophila pneumonia (LPP) identified using next-generation sequencing (NGS) for accurate identification.

Methods: This retrospective study included 68 patients with CPP and 42 patients with LPP. All cases were confirmed by metagenomic or targeted next-generation sequencing (mNGS/tNGS) of bronchoalveolar lavage fluid, serum, or sputum samples.

Results: Patients with LPP had a higher prevalence of diabetes and were predominantly male. Poultry contact was common in CPP (64.7% vs. 14.3%), whereas recent travel was associated with LPP (47.6% vs. 2.9%). LPP presented with increased extrapulmonary symptoms. Inflammatory marker levels were higher in LPP, including leukocytosis, neutrophilia, C-reactive protein, and procalcitonin (all p < 0.05). Organ dysfunction was more frequent in LPP, with higher creatinine levels. Patients with LPP had more severe hypoxemia, required more respiratory support, and had higher intensive care admission rates. Targeted therapy guided by NGS was effective, with no significant differences in mortality or hospital stay between the two groups.

Conclusion: LPP demonstrated greater initial clinical and laboratory severity compared to CPP. Under NGS-guided targeted therapy, both groups achieved comparable outcomes. The observational finding that both pathogens respond to azithromycin and cause severe disease when left undetected underscore the value of guideline-recommended β-lactams/macrolide combination therapy in CAP settings, particularly where these intracellular pathogens remain undiagnosed without NGS.

Background: Acute Ischemic Stroke (AIS) remains a critical global health challenge that requires continuous improvement in diagnostic strategies. Timely and accurate diagnosis is essential for effective reperfusion therapies such as intravenous thrombolysis and mechanical thrombectomy, whose clinical benefits rapidly diminish with treatment delays. Artificial Intelligence (AI) offers promising potential to enhance diagnostic accuracy and clinical decision-making in AIS. However, data fragmentation and strict privacy regulations limit the development of robust AI systems. Objectives: We aim to provide a perspective-style review that explores how collaborative AI can reshape AIS diagnostics by overcoming data access barriers, fostering cross-institutional model development, and improving diagnostic equity.

Methods: We analysed current challenges in developing AIS-related AI tools, particularly the limitations caused by restricted data sharing across healthcare institutions. The study highlights collaborative AI approaches, such as federated learning and privacy-preserving computation, which enable decentralised model training while maintaining patient confidentiality. Relevant literature and recent developments in clinical AI collaboration were reviewed.

Results: Collaborative AI enables multiple institutions to contribute to model training without exposing raw patient data. This approach improves data diversity, model generalizability, and fairness across healthcare settings. Evidence from multi-centre studies suggests that collaborative AI frameworks can produce more accurate and ethically compliant diagnostic models compared to isolated development efforts.

Conclusions: Collaborative AI presents a transformative pathway for AIS management by balancing data utility and privacy protection. It supports the creation of trustworthy, scalable, and inclusive diagnostic systems. As healthcare systems increasingly adopt digital solutions, collaborative AI provides a foundation for equitable and privacy-conscious innovation in stroke care.

Purpose: Behçet's disease (BD) is a multisystem autoinflammatory disorder that may present during childhood. Pediatric BD is challenging to diagnose due to heterogeneous clinical manifestations and the lack of standardised pediatric classification criteria. This study aimed to evaluate the association between systemic inflammatory biomarkers-including the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and C-reactive protein (CRP)/albumin ratio-and systemic organ involvement in children with BD. To our knowledge, no prior study has investigated these markers in pediatric BD.

Methods: In this retrospective study, 41 pediatric patients diagnosed with BD according to the 2015 PEDBD criteria and followed jointly by dermatology and rheumatology departments were included. Age- and sex-matched healthy controls (n = 41) undergoing elective surgery were also enrolled. Inflammatory indices (NLR, SII, PIV, CRP/albumin) were calculated from pre-treatment blood samples. Cut-off values for systemic involvement were determined via ROC analysis. Statistical analyses included the Kolmogorov-Smirnov test, independent t-test or Wilcoxon test, Chi-square and McNemar tests, correlation analysis, logistic regression, and ROC analysis.

Results: Systemic involvement was observed in 28 (68.3%) patients, including neurological involvement in 4 (9.8%), vascular involvement in 5 (12.2%), and other major organ involvement in 19 (46.3%). Inflammatory indices-PIV, SII, NLR, and CRP/albumin-were significantly higher in patients with systemic, neurological, and vascular involvement (all p < 0.05). Optimal cut-off values for each index were established based on systemic involvement.

Conclusion: Systemic inflammatory biomarkers such as NLR, SII, PIV, and CRP/albumin ratio may serve as useful indicators of systemic organ involvement in pediatric BD. Routine assessment of these markers could facilitate earlier recognition and more targeted management of systemic manifestations in this population.

Background: The triglyceride-glucose index (TyG) has gained attention as an alternative indicator for assessing insulin resistance (IR). The purpose of this study was to comprehensively summarize the correlation between the TyG index and cardiovascular events in patients with coronary revascularization.

Methods: PubMed, Web of Science, Embase, and The Cochrane Library databases were searched to find relevant literature on the prognostic assessment of TyG index in patients undergoing coronary artery revascularization. Utilize the risk ratio (RR) and its 95% confidence interval (CI) as the standard for assessing the correlation between TyG and major adverse cardiovascular events (MACEs) in patients undergoing coronary artery revascularization. Conduct sensitivity analysis and subgroup analysis to detect the sources of heterogeneity and assess the stability of the results.

Results: A total of 12 studies involving 9,973 participants were included. The results of the study indicate that a high TyG index was related to the major adverse cardiovascular event in patients undergoing coronary artery revascularization (RR:2.0,95%CI: 1.71-2.35, I²=76.2%, p < 0.0001). Subgroup analysis reveals that the probability of MACEs occurring in patients with high TyG index is higher than in those with low TyG index after two different coronary artery revascularization procedures: CABG group (RR:2.10, 95%CI:1.80-2.45, I2 = 20.9%, p = 0.0001). PCI group: (RR:1.94, 95%CI:1.54-2.46, I2 = 84.2%, p < 0.00001). Additionally, we also demonstrated the prognostic value of the TyG index in all-cause mortality(p = 0.003), non-fatal myocardial infarction(p = 0.003), non-fatal stroke(p < 0.0001) and repeat revascularization(p < 0.0001).

Conclusions: Higher TyG index may be independently associated with higher incidence of MACEs in patients with coronary revascularization.

Background: Tumour microenvironment and cancer cells have constant interaction affecting cancer progression. Tumour-stroma ratio (TSR) in the tumour centre and desmoplastic reaction (DR) classification at the invasive margin are prognostic factors based on stroma evaluation on H&E slides. However, their combined value and immunological associations remain poorly defined. This study examines the prognostic and immunological value of TSR, DR, and their combination in two large colorectal cancer cohorts.

Methods: Two colorectal cancer cohorts (N = 1,876) were analyzed. We introduced a three-tiered Stromal Maturity and Proportion Score (SMAPS) based on the presence of high (>50%) TSR and myxoid stroma (immature DR classification). Alcian blue staining was used to further quantify myxoid stroma. Multiplex immunohistochemistry combined with digital image analyses, was utilized to study immune cell densities associated with SMAPS, TSR, DR, and Alcian blue intensity.

Results: In the study cohort (N = 1,100), SMAPS was a stronger predictor of cancer-specific mortality [HR for high (vs. low) SMAPS 2.01 (95% CI 1.47-2.75), p < 0.0001] compared to TSR [HR for stroma-high (vs. stroma-low) 1.49 (95% CI 1.15-1.93), p = 0.003] and DR classification [HR for immature (vs. mature) 1.84 (95% CI 1.39-2.45), p < 0.0001]. High SMAPS, stroma-high TSR, and immature DR correlated with lower densities of CD3⁺ T cells, B cells, M1-like macrophages, CD66B⁺ granulocytes, and mast cells. Alcian blue staining was associated with immature DR and corresponding immune cells. The validation cohort (N = 776) confirmed the association of SMAPS with survival and T cell densities.

Conclusions: TSR and DR are independent prognostic factors for cancer-specific survival. SMAPS is a promising prognostic tool that integrates stromal maturity at the invasive margin and stromal proportion in the tumour centre. SMAPS has stronger prognostic value compared to TSR and DR classifications alone. A high stromal proportion and myxoid content are associated with an immunosuppressive microenvironment characterized by lower densities of antitumourigenic immune cells.