Nevin Manimala

Bone Marrow Transplant. 2026 Feb 14. doi: 10.1038/s41409-026-02803-6. Online ahead of print.

ABSTRACT

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape of relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (B-ALL), with high remission rates across various CAR T-cell constructs. However, the durability of these responses remains a major challenge, with many patients experiencing relapse after an initial remission. This systematic review and meta-analysis aimed to compare the efficacy and safety of different CAR T-cell constructs across 40 clinical trials, including a total of 1540 R/R B-ALL patients. We assessed the impact of patient demographics, prior treatment exposure, and construct characteristics on treatment outcomes. The pooled complete remission rate (CRR) was 83.4% (I² = 49%), with a minimal residual disease-negative complete remission (MRDneg-CR/CRi) rate of 92.7% (I² = 48%). 4-1BB co-stimulatory domain constructs showed higher MRDneg-CR/CRi rates compared with CD28 (94.0% vs. 84.4%p = 0.048) and a lower incidence of immune effector cell-associated neurotoxicity syndrome. Additionally, CAR T-cell products targeting CD19 or CD19/CD22 patients presented higher MRDneg-CR/CRi rates than those targeting CD22 alone. In conclusion, our findings suggest that 4-1BB-based CAR T-cell therapy targeting CD19 offers the best efficacy and safety profile in R/R B-ALL.

PMID:41691095 | DOI:10.1038/s41409-026-02803-6

Arch Gynecol Obstet. 2026 Feb 14;313(1):95. doi: 10.1007/s00404-026-08322-5.

ABSTRACT

PURPOSE: This study assessed geographic variations in the supply, demand, and adequacy of the United States (US) obstetrics and gynecology physician (OGP) workforce.

METHODS: This was a cross-sectional analysis of OGPs using the Health Workforce Simulation Model. Supply and demand were defined as the numbers of full-time equivalent (FTE) OGPs working and needed, respectively. Adequacy was defined as the ratio of supply to demand. Comparisons were made using Chi-squared tests, and linear regression was used to analyze OGP workforce trends.

RESULTS: From 2025 to 2037, the demand for OGPs is projected to increase (52,620-54,020 FTEs, 2.7% increase, p < 0.001) while the supply of OGPs is projected to decrease (49,170-44,130 FTEs, 10.3% decrease, p < 0.001). As a result, OGP workforce adequacy is projected to decrease over the study period from 93.4% to 81.7% (P < 0.001). By 2037, the West had the lowest OGP workforce adequacy and the Northeast had the highest adequacy (74.4% vs 98.6%, P < 0.001). Non-metropolitan areas were projected to have lower OGP workforce adequacy than metropolitan areas (51.4% vs 85.1%, p < 0.001). The states with the lowest projected OGP workforce adequacy were Utah (49.3%), Idaho (51.5%), and Arizona (58.3%) in 2037.

CONCLUSION: OGP workforce supply is expected to fall short of anticipated demand, with uneven geographic distribution across the US. Addressing this imbalance will require strategic planning to expand the OGP workforce equitably, especially in non-metropolitan areas, the West, and certain identified states like Utah and Idaho.

PMID:41691088 | DOI:10.1007/s00404-026-08322-5

Cytotherapy. 2025 Dec 27;28(4):102039. doi: 10.1016/j.jcyt.2025.102039. Online ahead of print.

ABSTRACT

PURPOSE: We sought to determine the impact of fetal growth restriction (FGR) on the cellularity of the amniotic fluid, with a focus on its mesenchymal stem cell (MSC) population.

METHODS: Four time-dated pregnant Sprague-Dawley dams were exposed to alternating 12-h hypoxia (10.5% O2) cycles from gestational day 15 (E15) until term (E21; FGR group). Three time-dated pregnant Sprague-Dawley dams not exposed to hypoxia served as normal controls. At term, fresh amniotic fluid samples from all their fetuses (n = 88, equally divided between the two groups) underwent quantitative multicolor flow cytometry for the detection of live cells as well as of cells concomitantly expressing CD29, and CD44 (both are markers of MSCs), while being also negative for DAPI and CD45, utilizing standard gating strategies. Statistical analysis was by Wilcoxon rank-sum tests and median regression (P < 0.05).

RESULTS: Placental efficiency was significantly lower in the FGR group compared to controls (P < 0.001), confirming reproduction of the disease model. There was no significant difference in the median individual amniotic fluid volume between the groups (P = 0.792). Compared to controls, FGR fetuses had statistically significantly lower densities of both total live cells as well as of live MSCs in the amniotic fluid (both P < 0.001). There was a significant decrease in the total number of MSCs in the FGR group versus controls (P < 0.001).

CONCLUSIONS: Native amniotic fluid MSC may be consumed in the setting of FGR. This provides further biological basis for transamniotic stem cell therapy as a potential novel treatment for this disease.

PMID:41689918 | DOI:10.1016/j.jcyt.2025.102039

Mult Scler Relat Disord. 2026 Feb 2;108:107045. doi: 10.1016/j.msard.2026.107045. Online ahead of print.

ABSTRACT

BACKGROUND: Mazandaran province in Iran, identified as a high-prevalence area, has lacked comprehensive long-term studies on MS trends. This study aims to fill that gap by analyzing three decades of MS incidence and prevalence in Mazandaran using advanced statistical methods.

METHODS: This longitudinal study included clinically diagnosed MS cases from the two most populous cities in Mazandaran utilizing data from the national MS registry spanning 1994 to 2023. Prevalence and age-adjusted incidence rates were calculated, and annual percentage change (APC) was assessed using joint point regression. Bayesian statistical methods were applied for comprehensive trend analysis.

RESULTS: A total of 1333 MS patients were identified, the mean (±sd) age at diagnosis was 28.58±8.52 years. MS prevalence increased from 0.19 per 100,000 in 1994 to 127.24 per 100,000 in 2023. The age-adjusted incidence rate rose from 0.14 (95 %CI: 0-0.5) in 1994 to a peak of 10.44 (95 %CI: 7.8-13.0) in 2018, then declined to 4.39 (95 %CI: 2.7-6.1) in 2023. The APC in MS incidence was +14.1 % until 2018, followed by a -15.32 % decrease thereafter. Significant differences in mean age, Expanded Disability Status Scale (EDSS) score and MS type were observed before and after 2018. The Bayesian methods indicated that evaluated predictors were not statistically significant for MS prevalence.

CONCLUSION: This study demonstrates a marked increase in MS incidence in Mazandaran province until 2018, followed by a subsequent decline. The rising prevalence and decreasing mean age at diagnosis underscore the need for continued surveillance and further research to determine whether the recent decline in incidence will persist.

PMID:41689909 | DOI:10.1016/j.msard.2026.107045

J Pediatr Nurs. 2026 Feb 13;88:34-43. doi: 10.1016/j.pedn.2026.02.007. Online ahead of print.

ABSTRACT

OBJECTIVES: This study investigated the effect of the puppet-assisted House-Tree-Person Test (HTP-T) on fear and anxiety levels in children undergoing chemotherapy treatment and the factors influencing these outcomes.

METHODS: The study employed a one-group pretest-posttest quasi-experimental design combined with HTP-T analysis. The study was conducted with 29 children aged 5-12 years receiving chemotherapy at the pediatric hematology-oncology outpatient clinics of a university hospital in the Eastern Black Sea Region of Türkiye during the 2022-2024 years. Data were collected using “the Demographic Information Form for Children and Parents, the Children’s State Anxiety Scale (CSA), the Children’s Fear Scale (CFS), and HTP-T”. Data analysis was performed using descriptive statistics, repeated measures ANOVA, and HTP-T analysis.

RESULTS: Statistically significant differences were observed in children’s mean CSA (F = 3.898, p = 0.026, η2 = 0.122) and CFS (F = 5.313, p = 0.008, η² = 0.159) scores across the pre-treatment, during-treatment, and post-treatment measurements. The HTP-T analysis revealed that children had difficulty regulating anxiety and fear, expressed concerns about family and environmental events, reported feelings of loneliness, and exhibited strong emotional attachment to their families.

CONCLUSION: The study demonstrated that incorporating puppet-assisted HTP-T during chemotherapy contributed to reducing children’s fear and anxiety and offered a useful approach for identifying influencing factors.

IMPLICATIONS FOR NURSING PRACTICE: HTP-T, a therapeutic play technique incorporating puppetry and projective methods, may be effective in reducing fear and anxiety among children undergoing chemotherapy.

PMID:41689903 | DOI:10.1016/j.pedn.2026.02.007

Lung Cancer. 2026 Feb 11;214:109315. doi: 10.1016/j.lungcan.2026.109315. Online ahead of print.

ABSTRACT

BACKGROUND: The tumor-associated microbiome influences cancer development and progression, yet the microbial landscape of small cell lung cancer (SCLC) remains unexplored. Given the absence of SCLC-specific microbiome studies, we conducted an exploratory analysis to describe the bacterial and fungal communities present in SCLC tissue.

RESULTS: Using 16S rRNA sequencing, we profiled the bacteriome of lung specimens from SCLC and control cases and observed increased bacterial signal and reduced bacterial diversity in SCLC, accompanied by relative enrichment of Firmicutes and Bacteroidota. Actinobacteria were comparatively underrepresented, resulting in a higher Proteobacteria-to-Actinobacteria ratio, although this difference did not reach statistical significance. At the genus level, SCLC samples were dominated by Pseudomonas, Streptococcus, Haemophilus, and Granulicatella, which together accounted for approximately half of the bacterial community. As a secondary, hypothesis-generating analysis, we examined the mycobiome using ITS sequencing and detected the unexpected presence of the biotrophic plant-pathogenic genus Taphrina in a subset (25%) of SCLC samples. Given the methodological constraints and contamination risks inherent to low-biomass FFPE tissues, this fungal signal is interpreted cautiously and framed strictly as preliminary.

CONCLUSIONS: This study provides the first descriptive characterization of the lung bacteriome and mycobiome in SCLC using FFPE tissue. The observed alterations in microbial composition, including an unexpected fungal signal, offer hypothesis-generating insights that require validation in larger, prospectively collected cohorts incorporating more comprehensive contamination-control strategies.

PMID:41689890 | DOI:10.1016/j.lungcan.2026.109315

Lung Cancer. 2026 Feb 4;214:109305. doi: 10.1016/j.lungcan.2026.109305. Online ahead of print.

ABSTRACT

BACKGROUND: Approximately 60 % of lung cancer cases occur in Asia, indicating an epidemiological disparity and need for effective therapies. Amivantamab-lazertinib is approved for first-line EGFR-mutated advanced non-small cell lung cancer (NSCLC) in many countries. In the protocol-specified final overall survival (OS) analysis of MARIPOSA (NCT04487080), amivantamab-lazertinib showed a statistically significant and clinically meaningful improvement in OS versus osimertinib (HR, 0.75; P = 0.005) among all participants. We evaluated OS for amivantamab-lazertinib versus osimertinib in Asian participants.

PATIENTS AND METHODS: Participants with previously untreated EGFR-mutated, locally advanced/metastatic NSCLC were randomized 2:2:1 to receive amivantamab-lazertinib, osimertinib, or lazertinib (for evaluating contribution of components). Self-identified Asian race was a stratification factor. OS was a key secondary endpoint.

RESULTS: Of 1074 randomized participants, 629 self-identified as Asian (amivantamab-lazertinib:250; osimertinib:251; lazertinib:128). At a median follow-up of 38.7 months, amivantamab-lazertinib significantly prolonged OS versus osimertinib among Asian participants. Median OS was not reached (NR; 95 % CI, NR-NR) for amivantamab-lazertinib versus 38.4 months (95 % CI, 35.1-NR) for osimertinib (HR, 0.74; 95 % CI, 0.56-0.97; nominal P = 0.026). Assuming exponential distribution of OS in both arms, amivantamab-lazertinib is projected to prolong median OS among Asian participants by > 12 months versus osimertinib. At 36 months, 61 % and 53 % were alive in the amivantamab-lazertinib and osimertinib arms. Safety profile was consistent with the overall population.

CONCLUSIONS: Consistent with the overall population, amivantamab-lazertinib significantly improved OS versus osimertinib among Asian participants with previously untreated EGFR-mutated advanced NSCLC, making it the first regimen to improve survival among Asian patients.

PMID:41689889 | DOI:10.1016/j.lungcan.2026.109305

Epidemics. 2026 Jan 21;54:100890. doi: 10.1016/j.epidem.2026.100890. Online ahead of print.

ABSTRACT

Early outbreak data analysis is critical for informing about their potential impact and interventions. However, data obtained early in outbreaks are often sensitive and subject to strict privacy restrictions. Thus, federated analysis, which implies decentralised collaborative analysis where no raw data sharing is required, emerged as an attractive paradigm to solve issues around data privacy and confidentiality. In the present study, we propose two approaches which require neither data sharing nor direct communication between devices/servers. The first approach approximates the joint posterior distributions via a multivariate normal distribution and uses this information to update prior distributions sequentially. The second approach uses summaries from parameters’ posteriors obtained locally at different locations (sites) to perform a meta-analysis via a hierarchical model. We test these models on simulated and on real outbreak data to estimate the incubation period of multiple infectious diseases. Results indicate that both approaches can recover incubation period parameters accurately, but they differ in terms of structure and complexity; which makes them suitable for different types of analyses or to be used in combination. We provide a framework for federated analysis of early outbreak data where the public health contexts are complex.

PMID:41689886 | DOI:10.1016/j.epidem.2026.100890

Int J Med Inform. 2026 Feb 3;211:106337. doi: 10.1016/j.ijmedinf.2026.106337. Online ahead of print.

ABSTRACT

BACKGROUND: Heterogeneity in the long-term progression of Alzheimer’s disease (AD) challenges the efficiency of clinical trials. Identifying long-term prognostic factors is critical for enhancing trial efficiency, although it has been limited by the lack of appropriate statistical approaches. We applied a recently developed statistical model-based AI method to identify the baseline prognostic factors for long-term cognitive decline in a clinical trial population.

METHODS: We analyzed pooled placebo arm data (N = 1,597) from four Phase III trials in patients with mild-to-moderate AD. Long-term trajectories for the Mini-Mental State Examination (MMSE), 11- and 14-item versions of the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog11, ADAS-Cog14), and Clinical Dementia Rating-Sum of Boxes (CDR-SB) were predicted from their short-term data (≤80 weeks). Trajectories were compared between subgroups defined by six baseline factors (age, sex, apolipoprotein E ε4 [APOE ε4] status, years of education, years from diagnosis, and years from disease onset) using the area under the curve (AUC).

RESULTS: Longer years of education (≥13 years) was the most robust predictor associated with faster progression across all four outcomes (e.g., for 20-year ADAS-Cog11, AUC ratio, 1.11, p < 0.001). Younger age (<74 years) was associated with a faster decline in MMSE and ADAS-Cog scores, but not in CDR-SB. APOE ε4 status, sex, years from diagnosis, and years from disease onset were not significantly associated with long-term progression.

CONCLUSIONS: Baseline educational level and age were significant prognostic factors of long-term cognitive decline. These findings will help optimize patient stratification in future clinical trials on AD.

PMID:41689882 | DOI:10.1016/j.ijmedinf.2026.106337

Urol Oncol. 2026 Feb 13;44(4):111006. doi: 10.1016/j.urolonc.2026.111006. Online ahead of print.

ABSTRACT

BACKGROUND: Adjuvant Intravesical BCG and chemotherapy are utilized viables options for intermediate-risk (IR) NMIBC. We are lacking well-designed evidence for superiority of any in terms of effectiveness, toxicity, and patient tolerability.

OBJECTIVES: We compared the oncological outcomes, treatment-related adverse events (AEs) and Health-related quality of life (HRQoL) in IR NMIBC patients who received intravesical BCG vs. intravesical Epirubicin.

MATERIALS AND METHODS: After institutional review board (IRB) approval, 134 patients were randomly allocated into two groups; adjuvant intravesical BCG and intravesical Epirubicin. Patients were followed every 3 to 6 months by cystourethroscopy and urine cytology. The primary end points were recurrence, progression, and disease-free survivals. The secondary end points comprised treatment-related AEs and quality of life using HRQoL-EORTC QLQ-30 questionnaire.

RESULTS: Of the 134 patients, 122 were followed for a mean of 19 months and included in the final analysis. There were no statistically significant differences between the two groups in terms of baseline demographic/tumor criteria. The tumor recurrence and progression rates were comparable between BCG vs. Epirubicin groups, (19.4% vs. 28.5%), (6.5% vs. 5%), respectively. Mean time to recurrence and RFS were significantly prolonged in BCG group (18 vs. 16.7 months, Log rank P = 0.02) While time to progression and PFS were statically comparable between the two groups (18.5 vs. 18.3 months, Log rank P = 0.76). Local treatment-related AEs as dysuria/urgency/frequency were significantly more reported in BCG group (19.5% vs. 10%, P = 0.03). BCG group experienced significantly worse HRQoL in terms of urinary symptoms and treatment-related future worries domains (P = 0.008, 0.001, respectively).

CONCLUSIONS: In patients with IR NMIBC, adjuvant intravesical therapy with BCG and Epirubicin are equivalent in terms of recurrence and progression rates. Nevertheless, RFS was significantly prolonged in patient receiving intravesical BCG. On the contrary, patients treated with BCG experienced significantly more local bladder symptoms and worse HRQoL in terms of bothering urinary symptoms and negative treatment-related future worries.

PMID:41689868 | DOI:10.1016/j.urolonc.2026.111006