原発性免疫不全症候群

Defining vaccine-induced protection in children with humoral immunodeficiency is essential to guide SARS-CoV-2 vaccination strategies in this high-risk population. We conducted a longitudinal analysis of SARS-CoV-2 immunity at 1, 6 and 12 months after a primary Pfizer-BioNTech mRNA vaccine series in 27 children aged 5-11 years with primary or secondary antibody deficiencies and 48 matched healthy controls. Functional T-cell responses were quantified by IFN-γ and IL-2 ELISpot, and SARS-CoV-2-specific B-cells and T-cells were assessed by spectral cytometry. Systemic and mucosal antibody responses were measured in serum and saliva, and neutralizing activity against ancestral and Omicron BA.5 strains was evaluated through microneutralization. Children with humoral immunodeficiency exhibited impaired systemic antibody responses after two mRNA doses, even after SARS-CoV-2 infection. A third dose improved humoral immunity in children with preserved B-cell compartments but did not rescue neutralizing antibody responses in those with severe B-cell lymphopenia. In contrast, preserved, polyfunctional SARS-CoV-2-specific T-cell responses were observed in children with humoral immunodeficiency, including those with severe B-cell lymphopenia, and were higher in asymptomatic immunocompromised children. These findings reveal a dissociation between humoral failure and preserved cellular immunity in B-cell-deficient children, supporting timely vaccination and integration of T-cell responses into vaccine-response assessment when neutralizing antibodies are absent.

PURPOSE: To identify predictors of recurrence in pediatric recurrent respiratory papillomatosis (RRP) using a 10-year prospective cohort, evaluating traditional factors (HPV type, lesion characteristics) and novel patient- and disease-specific variables, and their association with Speech-Quality-of-Life (SQOL). METHODS: We conducted a multicenter, prospective cohort study of 740 patients (629 pediatric, 111 adult) with histologically confirmed RRP from 2014 to 2023 at five high-volume ENT centers in Pakistan. The primary cohort comprised pediatric patients (onset < 18 years); while adult-onset cases were analyzed as a secondary comparative cohort to evaluate pediatric onset as an independent predictor of recurrence. Data included demographics, HPV type (6, 11, 16, 18), lesion number/location, surgery type, adjuvant therapy, tracheostomy history, age at onset, prior surgery intervals, lesion growth rate, socioeconomic status (SES), comorbidities, and immunodeficiency. The primary outcome was time to first recurrence requiring surgical intervention. Patients without recurrence were censored at their last follow-up visit. Time-to-event outcomes were analyzed using Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression adjusting for all covariates. Standardized lesion assessment demonstrated high inter-rater reliability (kappa = 0.78). RESULTS: Recurrence occurred in 65.0% of pediatric patients versus 45.9% of adult-onset patients (p < 0.001)Independent predictors included pediatric onset, HPV types 11, 16, 18, multiple lesions, tracheal involvement, younger age at onset, faster lesion growth, low SES, immunodeficiency, and shorter prior surgery intervals. Adjuvant therapies were associated with reduced recurrence (Cidofovir HR 0.62; Interferon HR 0.66; Bevacizumab HR 0.53). Surgery type did not independently predict recurrence. Median follow-up was 6.8 years. Lower SQOL scores correlated with higher recurrence frequency (Pearson r = - 0.52, p < 0.001). CONCLUSION: Recurrence in pediatric RRP is multifactorial. Novel predictors-lesion growth rate, SES, and immunodeficiency-enhance risk stratification. Adjuvant therapies show associative benefit, and SQOL correlates with recurrence, highlighting the clinical importance of functional outcomes.

INTRODUCTION: With the advent of modern therapies, including rituximab and novel oral targeted agents such as BTK inhibitors, the survival of lymphoma patients has significantly improved. However, the risk of secondary primary malignancies (SPMs) remains a critical concern. This study aims to evaluate the incidence, risk factors, latency, and survival outcomes of SPMs in lymphoma patients treated in the era of targeted therapies. METHODS: A retrospective cohort study was conducted on 1,715 lymphoma patients diagnosed between October 2011 and October 2024 at Shanxi Bethune Hospital, China. Patients with incomplete records, pediatric cases, or immunodeficiency were excluded. Data on demographics, lymphoma characteristics, treatment modalities, and SPMs were collected. SPMs were classified as synchronous (diagnosed within 6 months of lymphoma) or metachronous (diagnosed after 6 months). Statistical analyses included Cox regression for risk factors and Kaplan-Meier for survival analysis. RESULTS: Among 1,715 lymphoma patients, 65 (3.8%) developed SPMs, including 10 synchronous (0.6%, descriptive enumeration only), while 55 (3.2%) developed metachronous SPMs that constituted the primary analytic cohort. Aggressive B-cell non-Hodgkin lymphoma (43.6%) was the most common lymphoma subtype among patients who developed SPMs, followed by indolent B-cell non-Hodgkin lymphoma (38.2%). Digestive and respiratory system tumors were the predominant SPMs (34.5% and 23.6%, respectively). Multivariate analysis identified male sex, ECOG performance status ≥2, extranodal involvement, bone marrow infiltration, BTK inhibitor use, and radiotherapy as independent risk factors for SPMs. Competing-risk analysis showed a higher cumulative incidence of SPMs in patients exposed to BTK inhibitors than in those not exposed to BTK inhibitors (5-year CIF, 7.92% vs 2.57%; Gray's test [Formula: see text] =0.007). Kaplan-Meier analysis showed that patients with SPMs had significantly worse OS than those without SPMs (median OS, 10.3 years; 5-year OS, 69.6% vs 89.6%; log-rank [Formula: see text]<0.0001). No significant difference in OS was observed between patients with solid and hematologic SPMs (median OS, 12.8 vs 6.0 years; [Formula: see text]=0.76). DISCUSSION: In the transitional era of conventional and targeted therapies, although data are limited.This exploratory analysis confirmed that gastrointestinal and respiratory SPMs predominated in this Asian cohort, and identified male sex, ECOG ≥2, extranodal involvement, bone marrow infiltration, radiotherapy, and BTK inhibitor use as independent risk factors. The association with BTK inhibitors (HR=2.56) warrants cautious interpretation and prospective validation. Early detection and tailored surveillance (prioritizing gastrointestinal screening) are essential for improving long-term outcomes.

BACKGROUND: The treatment of depression is essential for improving both psychiatric and medical outcomes for youth with HIV (YWH). Previous studies have shown that the combination of a medication algorithm and CBT tailored for YWH (COMB) is efficacious for decreasing depressive symptoms and improving quality of life, but sustainability of effects remains difficult. Most recently, a cluster-randomized RCT found at Week 24 statistically significant improvement in the site-level mean number of depressive symptoms, the proportion of YWH with a treatment response, and the proportion in remission at COMB sites compared to treatment as usual (TAU) sites (6.7 vs. 10.6, 62% vs. 18%, 48% vs.17%, ps[Formula: see text]0.01, respectively). However, by Week 48, differences were no longer significant between arms for these outcomes. Additionally, viral suppression did not improve in COMB compared to TAU. These findings indicate a "voltage drop" of COMB's impact. To improve sustainability, we plan to enhance the combination treatment with five additional implementation strategies (COMBEX) suggested in our post-trial interviews from our efficacy study. This protocol paper describes a Hybrid Type 2 Cluster Randomized Trial in which COMBEX will be compared to COMB, with co-primary effectiveness and implementation aims guided by the Consolidated Framework for Sustainability Constructs in Healthcare. METHODS: Eligibility will include youth with HIV (15-24 years, n = 130) with a diagnosis of ongoing nonpsychotic depression at HIV clinic sites in the US. Using restricted randomization, sites (n = 8) will be assigned to either COMBEX (with its additional implementation strategies) or to COMB. Implementation outcomes of adoption, fidelity, and sustainability will be evaluated, as well as the impact of COMBEX compared to COMB in improving real-world effectiveness of reducing indices of depression (e.g., symptoms, treatment response, remission) and decreasing viral load over 72 weeks. Additionally, an explanatory, sequential, mixed-method approach will be used to evaluate the context of implementation for both COMB and COMBEX, guided by the sustainability framework with data from staff/clinicians (n = 64). Arm comparisons will use t-tests on site-level means. DISCUSSION: This study will inform the broader implementation of this efficacious approach to treatment of depression for youth with HIV by revealing strategies relevant to its sustainment. TRIAL REGISTRATION: NCT07211087 (registered October 7, 2025).

BACKGROUND: Non-acute decompensation (NAD) has been proposed as a distinct pathway of decompensation. This study evaluated the prognostic value of inflammatory mediators for subsequent clinical outcomes in patients with NAD. METHODS: Outpatients with NAD were included in this ambispective cohort study (Cohort 1 retrospectively; Cohort 2: prospectively). Patients were followed for 24 months. The primary endpoints were the occurrence of acute decompensation (AD), acute-on-chronic liver failure (ACLF), and liver-transplantation-free mortality. RESULTS: Cohort 1 ultimately comprised 373 patients. Cohort 2 included 192 patients. In multivariable analysis of cohort 1, both IL-10 and IL-6 levels independently predicted AD (log-transformed-IL-10, HR: 1.26; 95% confidence interval, CI: 1.16-1.36; P < 0.001; log-transformed-IL-6, HR: 1.13; 95% CI: 1.01-1.27; P = 0.03) and ACLF (log-transformed-IL-10, HR: 2.03; 95% CI: 1.57-2.64; P < 0.001; log-transformed-IL-6, HR: 2.21; 95% CI: 1.57-3.11; P < 0.001). Patients were stratified into three groups: no systemic inflammation (SI), SI without immunodeficiency (ID), and SI with ID (elevated IL-6 + IL-10). While SI alone increased AD risk, the coexistence of ID markedly amplified the risk of severe outcomes. Compared to SI alone, patients with SI + ID had a substantially higher risk of ACLF (Cohort 1 (training) HR: 28.02; 95% CI: 12.54-62.62; Cohort 2 (validating) HR: 39.78; 95% CI: 10.97-144.30). Nearly all deaths occurred in the SI + ID subgroup [Cohort 1: 10/10; Cohort 2: 4/5]. CONCLUSIONS: A combined biomarker profile of SI (IL-6) and ID (IL-10) identifies a distinct high-risk subgroup among NAD outpatients, characterized by a markedly elevated risk of progression to AD, ACLF and liver-transplantation-free mortality.