Category: Nevin Manimala

Int J Hematol. 2025 Nov 10. doi: 10.1007/s12185-025-04095-w. Online ahead of print.

ABSTRACT

This phase 2 study (NCT05105841) evaluated the safety and efficacy of a fixed-duration 12-cycle regimen of venetoclax plus obinutuzumab in Japanese patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The primary efficacy endpoint was the complete remission (CR)/complete remission with incomplete marrow recovery (CRi) rate, assessed by an independent review committee (IRC) according to the 2008 International Workshop on CLL criteria. Ten patients (6 male, 4 female; 9 CLL, 1 SLL) with a median age of 69.5 years (range 52-76) received venetoclax for a median duration of 11.3 months (range 9.2-12.4). The IRC-assessed CR/CRi rate based on the best overall response was 90.0% (95% confidence interval 55.5%, 99.7%). All patients experienced at least one treatment-emergent adverse event (TEAE), and three patients (30.0%) experienced at least one serious TEAE. The most common TEAEs included infusion-related reactions (60.0%), decreased neutrophil count (50.0%), and nausea (40.0%). Nine patients (90.0%) experienced TEAEs related to venetoclax, while all ten patients (100.0%) had TEAEs related to obinutuzumab. One patient (10.0%) developed COVID-19 pneumonia, necessitating the discontinuation of venetoclax. These findings demonstrate the high efficacy and manageable safety profile of venetoclax plus obinutuzumab in this patient population.

PMID:41212498 | DOI:10.1007/s12185-025-04095-w

Target Oncol. 2025 Nov 10. doi: 10.1007/s11523-025-01177-x. Online ahead of print.

ABSTRACT

BACKGROUND: Adavosertib is a highly selective, small molecule Wee1 inhibitor that sensitizes tumor cells to cytotoxic agents.

OBJECTIVE: We report results from the lead-in cohorts of two phase II studies: carboplatin/pemetrexed plus adavosertib versus carboplatin/pemetrexed in first-line metastatic non-squamous non-small-cell lung cancer (NSCLC) (NCT02087241); and docetaxel plus adavosertib versus docetaxel in recurrent NSCLC (NCT02087176).

PATIENTS AND METHODS: Both lead-in cohorts assessed early safety and efficacy (objective response rate [ORR]). First-line metastatic treatment was carboplatin (area under the curve to 6 h [AUC₆]) plus pemetrexed 500 mg/m² intravenously on day 1, every 21 days; recurrent treatment was docetaxel 75 mg/m² intravenously on day 1 plus prophylactic granulocyte-colony stimulating factor 6 mg subcutaneously on day 4 every 21 days. All patients received adavosertib 225 mg twice daily orally on days 1-3 (five doses). After a planned safety analysis of the first-line trial, dose and schedule were modified to reduce toxicity.

RESULTS: First-line: 14 patients were enrolled in four treatment cohorts. Median time on trial was 17.3 weeks, with an ORR of 29%. The most common adverse events were diarrhea (50%), nausea (50%), vomiting (50%), anemia (43%), neutropenia (43%), decreased appetite (43%), and dehydration (43%). Recurrent: 32 patients were enrolled. The ORR was 9%. The most common adverse events were diarrhea (66%), anemia (50%), nausea (47%), fatigue (47%), vomiting (44%), and thrombocytopenia (41%).

CONCLUSIONS: Both studies terminated early; the recurrent study after an interim analysis showed increased toxicity and limited efficacy, and the first-line study after a change in first-line standard of care.

TRIAL REGISTRATIONS: ClinicalTrials.gov, NCT02087241 and NCT02087176.

PMID:41212474 | DOI:10.1007/s11523-025-01177-x

Obes Surg. 2025 Nov 10. doi: 10.1007/s11695-025-08368-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Given the global increase in obesity prevalence, there has been an emergence of a multitude of treatment options, specifically less invasive operations, like intragastric balloons, and pharmaceutical treatments like semaglutide. The aim of this study is to evaluate the synergistic effects of the intragastric balloon and semaglutide on weight reduction and weight regain.

METHODS: In this prospective, randomized cohort, adults between the ages of 18 and 65, with a BMI of at least 27 kg/m², were assigned to one of two treatment groups: IGB only or IGB + semaglutide. Subcutaneous injections of semaglutide were administered with increasing dosages on a weekly basis in the second month and were continued after the removal of the intragastric balloon. All participants were monitored, and results were recorded at 3, 6, and 12 months.

RESULTS: Forty patients completed the study (n = 20 per group). The IGB + semaglutide group lost more weight than the IGB only group at 3, 6, and 12 months, with statistically significant differences at 6 months (29.09 ± 3.45 kg vs. 18.35 ± 2.80 kg, p < 0.001) and 12 months (33.03 ± 3.55 kg vs. 15.56 ± 2.50 kg, p < 0.001). After intragastric balloon removal at 6 months, the IGB only group regained previously lost weight while the IGB + semaglutide group continued to lose weight (2.79 ± 1.74 vs. -3.94 ± 2.16, p < 0.001).

CONCLUSION: Adjunctive semaglutide therapy with intragastric balloon (IGB) optimizes weight loss, while enhancing the sustainability achieved with intragastric ballooning alone. This combined therapeutic approach may provide an additional non-invasive intervention that provides optimal results and long-term weight loss maintenance.

PMID:41212463 | DOI:10.1007/s11695-025-08368-5

Odontology. 2025 Nov 10. doi: 10.1007/s10266-025-01256-5. Online ahead of print.

ABSTRACT

This study evaluated the effects of three chelating agents-glycolic acid (GA), ethylenediaminetetraacetic acid (EDTA), and etidronic acid (HEDP)-combined with different irrigation activation techniques on the pushout bond strength of Biodentine to root dentin after calcium hydroxide removal. A total of 120 extracted single-rooted mandibular premolars were randomly assigned to nine experimental and one control group (n = 12). Following Ca(OH)₂ dressing and incubation, canals were irrigated with GA, EDTA, or HEDP, each activated using passive ultrasonic irrigation (PUI), XP-Endo Finisher (XPF), or conventional needle irrigation (CNI). Biodentine was placed into 2 mm-thick root slices, and pushout bond strength was measured using a universal testing machine. Statistical analysis was performed using one-way ANOVA for group comparisons, and two-way ANOVA was used to evaluate factor effects (α = 0.05). Overall, GA produced higher bond strength than EDTA (p = 0.027). The difference between GA and HEDP was not significant under PUI activation; however, GA yielded significantly higher bond strength than HEDP when activated with CNI or XPF. Using 10% GA with PUI enhanced Biodentine-dentin adhesion, suggesting its potential as a biocompatible and effective alternative to conventional chelators in regenerative endodontic treatments, improving coronal sealing and long-term stability.

PMID:41212455 | DOI:10.1007/s10266-025-01256-5

Jpn J Radiol. 2025 Nov 10. doi: 10.1007/s11604-025-01908-0. Online ahead of print.

ABSTRACT

PURPOSE: Observation of the clearance of gadolinium-based contrast agents (GBCA) in patients with cerebral infarction and Moyamoya disease (MMD) using vessel-wall MRI (VW-MRI).

METHODS: This prospective study included 11 patients with recent cerebrovascular disorder and 6 patients with MMD who were scheduled for VW-MRI. All participants underwent whole brain delay alternating with nutation for tailored excitation-prepared T1-weighted variable flip angle turbo spin echo (DANTE T1-SPACE) imaging before, immediately after, and 1-6 h after gadolinium injection. Additionally, a phantom experiment was conducted to assess the signal intensity according to T1 values using DANTE T1-SPACE and 3D real inversion recovery sequences.

RESULTS: All five large infarction cases (≥ 5 cm) had delayed meningeal enhancement on the ipsilateral side, while none of the remaining six small infarction cases (< 5 cm) exhibited delayed meningeal enhancement on MRI. More than half of the entire cases had delayed white matter enhancement adjacent to the infarction. No MMD cases showed delayed enhancement outside postoperative regions. In the phantom experiment, DANTE T1-SPACE (TR = 700-1300 ms) demonstrated stable signal intensity across a T1 range of approximately 500-1000 ms. This T1 range corresponds to signal intensity ≈ 200-600 typically observed in regions showing delayed enhancement in clinical stroke and MMD cases.

CONCLUSIONS: Delayed meningeal enhancement observed in patients with large cerebral infarctions likely reflects alterations in brain clearance pathways. The absence of such enhancement in MMD supports that these enhancements are not attributable to collateral circulation. Phantom validation confirmed that the imaging parameters used in the DANTE T1-SPACE sequence were sufficient to detect subtle contrast enhancement in the clinically relevant T1 range.

PMID:41212449 | DOI:10.1007/s11604-025-01908-0

Curr Allergy Asthma Rep. 2025 Nov 10;25(1):52. doi: 10.1007/s11882-025-01234-5.

ABSTRACT

PURPOSE OF REVIEW: The optimal management of mucosal tissues during endoscopic sinus surgery (ESS) for chronic rhinosinusitis with nasal polyps (CRSwNP) remains controversial. This systematic review and network meta-analysis aimed to compare the efficacy and safety between mucosa-preserving surgical techniques, such as functional endoscopic sinus surgery (FESS) and extended endoscopic sinus surgery (EESS), and radical mucosa-resecting endoscopic sinus surgery (RESS) for the treatment of CRSwNP.

RECENT FINDINGS: Nine studies involving 1,224 patients were included. RESS was associated with significantly lower recurrence rates compared to both FESS (relative risk [RR]: 2.37; 95% confidence interval [CI]: 1.64, 3.43) and EESS (RR: 2.22; 95% CI: 1.48, 3.36). EESS demonstrated a significantly lower revision surgery rate than FESS (RR: 2.95; 95% CI: 1.89, 4.82). Additionally, RESS showed greater improvement in overall symptom/severity visual analogue scale (VAS, 0-10 cm) scores compared to FESS (mean difference [MD]: -2.82, 95% CI: -3.02, -2.62) and EESS (MD: -2.64, 95% CI: -4.09, -1.21). No significant differences were observed in complication rates among these surgical techniques. Besides, no statistically significant differences were found in VAS-loss of smell score, Sino Nasal Outcome Test-22 score, or Lund-Kennedy endoscopic score. Mucosal resection during endoscopic sinus surgery is associated with reduced postoperative recurrence and improved overall symptom control in patients with CRSwNP compared to mucosal preservation techniques. The safety profiles of these surgical approaches are comparable.

PMID:41212426 | DOI:10.1007/s11882-025-01234-5

Langenbecks Arch Surg. 2025 Nov 10;411(1):7. doi: 10.1007/s00423-025-03906-2.

ABSTRACT

BACKGROUND: Perioperative nutrition is a cornerstone of enhanced recovery in gastrointestinal cancer surgery, with international guidelines recommending early oral intake and standardized screening. This study aimed to assess current perioperative nutrition practices in German surgical departments and evaluate their alignment with guideline-based recommendations.

METHODS: A nationwide cross-sectional survey was conducted between September 18, 2024, and January 2, 2025, involving surgical departments that perform major gastrointestinal cancer resections. The 93-item anonymous questionnaire addressed pre- and postoperative nutrition strategies related to esophagectomy, gastrectomy, pancreatoduodenectomy and colorectal resections. Descriptive statistics were used to analyse the responses.

RESULTS: A total of 263 hospitals participated in the survey. More than one-third of hospitals (35.1%) reported no routine preoperative malnutrition screening and only 6.7% performed a structured nutritional assessment. There was no consistent agreement on postoperative feeding strategies including the timing of oral intake especially in upper gastrointestinal surgery. Nasogastric tubes were routinely placed postoperatively in 66 .1% of gastrectomies, 63.5% of esophagectomies, and 64.6% of pancreatoduodenectomies, but timing of postoperative removal varied widely. Hospitals with higher levels of care (e.g. university or maximum care hospitals) were significantly more likely to perform routine malnutrition screening (p = 0.002) and to allow early drinking after colorectal surgery (p < 0.001). The presence of structured nutrition support teams was associated with higher rates of guideline-compliant preoperative screening (76.3% vs. 47.4%; p < 0.001).

CONCLUSION: Perioperative nutrition practices in German gastrointestinal cancer surgery vary considerably and often deviate from established guidelines.These findings underline the need for greater standardization and broader adoption of evidence-based perioperative nutrition strategies to ensure optimal patient outcomes.

PMID:41212414 | DOI:10.1007/s00423-025-03906-2

Eur J Pediatr. 2025 Nov 10;184(12):744. doi: 10.1007/s00431-025-06608-5.

ABSTRACT

Intracerebral abscesses, although rare in children, represent the most frequent intracranial suppurative infection in children They typically present insidiously and can cause serious complications. Advances such as imaging-guided aspiration and prolonged antibiotics with good central nervous system penetration have improved clinical management. This study presents our single-centre experience over more than three decades, evaluating the impact of evolving therapeutic strategies on outcomes in children. We retrospectively analysed all patients admitted to our centre with confirmed brain abscesses between January 1988 and April 2020. Clinical details, surgical techniques, antibiotic management, and outcomes were collected from clinical charts. Patients were divided into two periods: A (1988-2005) and B (2006-2020). Statistical analysis compared clinical characteristics and outcomes between the two periods. Thirty-two children were included (mean age 5.4 ± 4.4 years): 18 in Period A and 14 in Period B, with positive cultures in 19. Twelve fully recovered, while 20 experienced clinical, radiological, or electroencephalographic sequelae. Younger patients had more severe disease: with larger abscesses under 4.9 years (p = 0.009); and multiple abscesses under 2 years (p < 0.001). Patients with sequelae were younger (p = 0.012), had Intraventricular Rupture of Brain Abscess, IVROBA, (p = 0.002), and multiple abscesses (p = 0.018). Comparing periods, baseline characteristics and corticosteroid administration were similar. IVROBA occurred only in Period A (7/18; p = 0.010). From 2006, management transitioned entirely to stereotactic aspiration with prolonged antibiotics, reducing clinical (p = 0.019) and radiological sequelae (p = 0.005). Mortality was 6.5% overall, occurring only in Period A.

CONCLUSION: Younger children are at higher risk of severe intracerebral abscesses and poorer prognosis. Introduction of standardised protocols including minimally invasive neurosurgery and prolonged antibiotic therapy has led to marked improvements, contributed to a significant reduction in both clinical and radiological sequelae, and effectively eliminated mortality in recent years.

WHAT IS KNOWN: • Intracerebral abscesses in paediatric population are rare. • Younger age is associated with more severe disease.

WHAT IS NEW: • Based on over three decades of single-center experience, the adoption of standardized protocols integrating microbiological evaluation, less invasive neurosurgical techniques, and optimized antibiotic regimens has significantly improved outcomes, virtually eliminating mortality.

PMID:41212413 | DOI:10.1007/s00431-025-06608-5

RSC Adv. 2025 Nov 7;15(51):43322-43333. doi: 10.1039/d5ra05719a. eCollection 2025 Nov 6.

ABSTRACT

Point-of-care (PoC) detection of antibodies in blood enables rapid, on-site diagnosis. However, these devices often face challenges related to user variability due to the requirement of multiple manual operations. To address this issue, we designed and developed a disposable microfluidic device that requires minimal user input for rapid detection of SARS-CoV-2 antibodies (ABs) in total blood and antigens associated with blood types. Here, we present a passive pressure-driven pumping technique that rapidly mixes blood samples with reagents, delivering results within three minutes. The device requires 15 μL of capillary blood and can detect SARS-CoV-2 ABs across a concentration range of 0 to 60 μg mL^-1. Additionally, we demonstrated the versatility of the microfluidic device by implementing blood typing functionality, highlighting its potential for broader serological testing applications. We also developed a support vector machine (SVM) algorithm as a proof-of-concept to demonstrate the potential application of machine learning (ML)-based analysis to complement visual interpretation of results. We evaluated the performance and predictive accuracy of the SVM model and compared it to human interpretations. The analysis showed that the SVM model achieved a statistically significant improvement in predicting varying degrees of agglutination when compared to human interpretation. This device addresses the need for a user-friendly, rapid COVID-19 AB testing solution and blood-typing assay and also provides a model for the future development of diagnostic devices that are integrated with ML models for improved diagnostic accuracy and accessibility in both clinical and non-clinical environments.

PMID:41209517 | PMC:PMC12593424 | DOI:10.1039/d5ra05719a

Alpha Psychiatry. 2025 Oct 21;26(5):47535. doi: 10.31083/AP47535. eCollection 2025 Oct.

ABSTRACT

BACKGROUND: The purpose of this study was to investigate the incidence of comorbid type 2 diabetes mellitus (T2DM) and its associated risk factors in adult patients with severe mental disorders (SMD) who were admitted to the Affiliated Brain Hospital of Guangzhou Medical University.

METHODS: We conducted a retrospective analysis of the clinical data of adult patients with SMD admitted to our hospital. The research comprised 5964 adult inpatients with SMD. Data were collected from 1 January 2023, to 31 December 2023. The collected data encompassed demographic details, classifications of mental disorders, hospitalization records, concomitant conditions, and pertinent laboratory findings. We performed descriptive and inferential statistical analyses to assess the prevalence of T2DM and identify associated risk factors.

RESULTS: Patients with SMD had a 10.14% frequency of concurrent T2DM. In this patient cohort, our study found that age, body mass index (BMI), hypertension, triglyceride levels and apolipoprotein B levels were important risk factors for T2DM.

CONCLUSION: The results show that T2DM is much more common in people with SMD and suggest that several clinical and demographic traits may increase the chance of developing this condition. Extensive screening and targeted treatments are necessary for this vulnerable group.

PMID:41209502 | PMC:PMC12593731 | DOI:10.31083/AP47535