Current Medical Research and Opinion最新文献

Objective: To assess the real-world efficacy and safety of immunotherapy in small cell lung cancer (SCLC) across multiple lines of treatment.

Methods: We conducted a single-center, retrospective cohort study analyzing clinical data from 397 SCLC patients treated at the Second People's Hospital of Yichang (January 2018-July 2024). Based on treatment strategies, patients were divided into four groups: (1) first-line immune checkpoint inhibitor (ICIs)-based combination therapy, (2) first-line chemotherapy, (3) later-line ICIs-based combination therapy after first-line chemotherapy, and (4) chemotherapy in all lines. Propensity score matching (PSM) was used to balance baseline characteristics. Survival outcomes and safety were evaluated.

Results: After matching, baseline characteristics were comparable. In patients with extensive-stage SCLC (ES-SCLC), first-line ICIs‑based combination therapy significantly improved median overall survival (OS, 12.9 vs. 10.2 months; hazard ratio [HR] = 0.56, 95% CI 0.38-0.80; p = 0.00189) and median progression-free survival (PFS, 8.0 vs. 5.6 months; HR = 0.57, 95% CI 0.40-0.80; p = 0.00125) compared with chemotherapy alone. In the limited-stage cohort, first-line ICIs‑based combination therapy yielded numerically longer OSOS (40.0 vs. 15.5 months; p = 0.121), though results are preliminary and should be interpreted with caution given sample limitations. In the later-line setting, ICIs‑based combination therapy significantly extended median OS compared with chemotherapy (10.4 vs. 7.4 months; HR = 0.60, 95% CI 0.37-0.98; p = 0.0405). Exploratory analysis indicated longer OS with later-line versus first-line ICIs (22.6 vs. 12.6 months; HR = 2.44, 95% CI 1.12-5.33; p = 0.0255); however, this finding may be influenced by potential selection biases and guarantee-time bias and should be viewed as hypothesis-generating only. Immune-related adverse events (irAEs) occurred in 11.1-22.2%, indicating manageable toxicity.

Conclusion: Immunotherapy, whether first-line or later-line, improves survival in ES-SCLC with acceptable safety. Our exploratory results suggest that later-line immunotherapy may be associated with favorable survival trends; however, these findings are hypothesis-generating and require validation in prospective trials due to inherent selection biases.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome characterized by diastolic dysfunction in the context of elevated left ventricular filling pressures leading to clinical symptoms such as dyspnea, fluid retention and lethargy. Systemic microvascular dysfunction plays a key role in the pathophysiology of HFpEF, contributing to impaired tissue perfusion, endothelial dysfunction, and increased cardiovascular morbidity. Due to significant morbidity and mortality associated with the condition, there is a clear need for early detection and risk stratification. This narrative review aims to explore the use of retinal imaging as a non-invasive tool for detecting systemic microvascular dysfunction and its implications as a biomarker for HFpEF. A comprehensive search of the literature was performed, and relevant studies were identified for inclusion based on their relevance to microvascular dysfunction and retinal changes in HFpEF. While N-terminal pro-B-type natriuretic peptide (NT-proBNP) and transthoracic echocardiography remain the diagnostic gold standard, retinal vascular changes have shown potential for both diagnostic and prognostic applications in HFpEF. Retinal biomarkers provide unique insights into microvascular dysfunction. Early studies support integrating these biomarkers for detection and risk stratification in future clinical guidelines. However, further research is needed to validate their predictive value and feasibility as standardized biomarkers for HFpEF assessment.

Introduction: Topical hydrocortisones are commonly used for the self-treatment of allergic or mild inflammatory skin reactions. Post-market data analyzing usage, safety and effectiveness of hydrocortisone creams in a real-world setting are scarce.

Methods: This non-interventional, observational, pharmacy-based study analyzes the usage patterns and patient-perceived effectiveness and tolerability of Soventol Hydrocortisonacetat 0.5% (Soventol HCA) in a real-world setting. Adult participants with a moderately pronounced reddened, inflammatory or allergic skin disease for which a weak, low-concentration corticosteroid was indicated filled an online questionnaire parallel to product application for a maximum of 7 days. Severity of symptoms, frequency of application and the occurrence of adverse events were documented daily. The study was reported to the German Federal Institute for Drugs and Medical Devices (NIS-nr 7793).

Results: Data from 2,561 participants were received. Most participants used Soventol HCA for the treatment of insect bites (62.3%; N = 2,557). Almost all participants were "very satisfied" or "satisfied" with the effectiveness (97.7%; N = 2,106) and tolerability (99.1%; N = 2,106) of Soventol HCA. The vast majority of participants assessed the speed of itching relief (87.0%; N = 2,045), speed of cooling effect (90.5%; N = 2,073), pain relief (93.9%; N = 1,760), redness relief (90.2%; N = 2,033), and swelling relief (92.9%; N = 1,901) as "fast" to "very fast" or "good" to "very good." 61 non-serious adverse reactions were documented.

Conclusion: This non-interventional study provides valuable real-world insights about the patient-perceived effectiveness and tolerability of Soventol HCA in treating insect bites, but also other inflammatory or allergic skin reactions as e.g. sunburn, allergies or eczema in adults. Patient satisfaction with effectiveness and tolerability was high in all application fields, especially regarding itch reduction of insect bites.

Objective: This study explored the perspectives of people with HIV (PWH) in the United States regarding barriers and facilitators of engaging with HIV care, focusing on treatment initiation, satisfaction, adherence, and preferences.

Methods: An observational, cross-sectional, quantitative online survey was conducted from 2024 through 2025 among eligible PWH aged ≥18 years. The survey was carried out globally; we report results from PWH who reside in the United States. Survey questions assessed sociodemographic, sociobehavioral, and clinical characteristics; HIV diagnosis and linkage to care; and HIV treatments and treatment success. The survey included the validated HIV Treatment Satisfaction Questionnaire (HIVTSQ). Results were analyzed for subgroups of interest. Data were summarized descriptively; formal statistical comparisons were conducted.

Results: A total of 402 PWH participated in the survey. Rapid antiretroviral therapy (ART) initiation was deemed "important"/"very important" by 93% of participants, yet 73% of PWH ever treated did not start treatment within 7 days of diagnosis and 29% started after >30 days. Common reasons for delayed treatment included fear of side-effects, physician recommendation, and needing time to accept the diagnosis. The median HIVTSQ score for overall treatment satisfaction was 51.0/60.0, with numerically higher satisfaction observed among those aged ≥50 years (57.0), not using drugs (54.0), and on bictegravir/emtricitabine/tenofovir alafenamide (57.0). The most important features to stay on treatment were long-term tolerability and efficacy.

Conclusion: Despite the recognized importance of rapid ART initiation, almost one-third of participants ever treated started treatment >30 days after diagnosis. These findings can support tailored strategies to enhance rapid ART initiation and treatment adherence and satisfaction, thereby improving health outcomes for PWH.

Background/objective: Disordered mineral metabolism is associated with adverse outcomes in dialysis populations, but its prognostic significance in non-dialysis CKD is less well defined. This study evaluated elevated serum alkaline phosphatase (ALP) and hyperphosphatemia as predictors of mortality and renal outcomes in non-dialysis CKD.

Methods: In this prospective cohort study, patients from a tertiary renal clinic were followed for >12 months. Elevated ALP was defined as >105 U/L in females or >130 U/L in males; hyperphosphatemia as phosphate >4.5 mg/dL. The primary outcome was mortality, and the secondary outcome was a composite endpoint (ESKD progression, dialysis initiation, or doubling of serum creatinine). Kaplan-Meier, log-rank, and Cox regression analyses were performed (STATA; p <.05).

Results: Among 360 patients (mean age 53.7 ± 13.9 years; follow-up 14 ± 4.2 months), elevated ALP was present in 31.7% and was associated with higher mortality (24.6% vs 8.9%, p <.001) and composite events (45.6% vs 33.9%, p = .03). Hyperphosphatemia occurred in 38.1% and was associated with increased mortality (21.2% vs 9.4%, p = 0.002) and composite outcomes (57.4% vs 25.6%, p <.001). Elevated ALP independently predicted mortality (HR = 2.37; 95% CI = 1.36-4.15; p = .002) but not composite outcomes. Hyperphosphatemia predicted both mortality (HR = 2.59; 95% CI = 1.47-4.57; p = .001) and composite events (HR = 2.55; 95% CI = 1.80-3.60; p <.001). Subgroup analyses demonstrated the highest mortality risk among patients with concurrent elevations in ALP and serum phosphate.

Conclusions: Elevated ALP independently predicted mortality, while hyperphosphatemia predicted both mortality and CKD progression. Monitoring these biomarkers may improve risk stratification and guide future interventional studies.

Objective: In the phase 3 RATIONALE-312 trial (ClinicalTrials.gov Identifier: NCT04005716), the addition of tislelizumab to chemotherapy as first-line treatment significantly improved overall survival and progression-free survival compared to placebo plus chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC), with an acceptable safety profile. This analysis reports the patient-reported outcomes (PROs) from RATIONALE-312.

Methods: Overall, 457 adults with ES-SCLC were randomized (1:1) to tislelizumab plus chemotherapy (n = 227) or placebo plus chemotherapy (n = 230). PROs were protocol-prespecified secondary end points that assessed health-related quality of life (HRQoL) using the EORTC QLQ-C30 and EORTC QLQ-LC13 questionnaires. PRO end points at Cycles 4 and 6 were analyzed using a mixed model for repeated measures. Time to deterioration (TTD) was evaluated.

Results: At Cycle 4, the tislelizumab arm demonstrated clinically meaningful improvement in coughing, hemoptysis, and chest pain. Clinically meaningful improvement was observed in the tislelizumab arm, but not in the placebo arm, for global health status (GHS)/QoL, dyspnea, and arm or shoulder pain. By Cycle 6, the tislelizumab arm achieved clinically meaningful improvement in GHS/QoL, with a statistically significant between-group difference favoring the tislelizumab arm. Clinically meaningful improvements in dyspnea, coughing, hemoptysis, and chest pain were maintained in the tislelizumab arm through Cycle 6. No between-group differences were observed in the TTD analysis.

Conclusions: Tislelizumab plus chemotherapy maintained or improved HRQoL and patient-reported symptoms compared to placebo plus chemotherapy. Along with prior efficacy and safety data, these data support tislelizumab plus chemotherapy as first-line treatment in patients with advanced ES-SCLC.

Background: This study presents patient-reported outcomes (PROs) from the phase 1/2 BRUIN (NCT03740529) trial of pirtobrutinib monotherapy for the treatment of B-cell malignancies, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL).

Methods: PROs were collected at each cycle using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and item library (IL) sets for CLL/SLL- and MCL-related symptoms and an Expanded Fatigue measure. Prespecified analyses included descriptive change from baseline, time to worsening (TTW) using Kaplan-Meier method, and longitudinal analyses using a mixed model for repeated measures.

Results: A total of 263 patients with CLL/SLL and 124 with non-blastoid MCL who received pirtobrutinib monotherapy after prior BTKi were included in the final PRO analysis. The proportion of patients with CLL/SLL who improved or remained stable from baseline through Cycle 31 remained above 80% for physical function (PF), CLL/SLL-related symptoms, fatigue, and global health status/quality of life (GHS/QoL). The proportion of patients with MCL who improved or remained stable through Cycle 20 remained above 70% for PF, MCL-related symptoms, fatigue, and GHS/QoL. Median TTW was not reached in either CLL or MCL. Longitudinal analyses for PF, CLL/SLL-related symptoms, fatigue, and GHS/QoL consistently met statistically significant and clinically-meaningful improvement from baseline for CLL. PRO assessments remained stable over time for MCL.

Conclusions: The final analysis from the BRUIN trial demonstrates stability in PROs throughout the duration of treatment with pirtobrutinib. Most patients with CLL/SLL and MCL reported stable or improved outcomes throughout the study.