Category: Nevin Manimala

Pharmacotherapy. 2026 Jan;46(1):e70102. doi: 10.1002/phar.70102.

ABSTRACT

BACKGROUND: Although donor-derived cell-free DNA (dd-cfDNA) serves as a monitoring tool for rejection, few studies have examined its utility in guiding immunosuppression management. Here, we present the largest kidney transplant population in which immunosuppression minimization and subsequent surveillance were guided by dd-cfDNA.

METHODS: This retrospective case series evaluated our immunosuppression minimization practice to tacrolimus and prednisone in kidney transplant recipients (KTR) from November 20, 2020, to September 26, 2024. Baseline dd-cfDNA ≤ 0.5% was required before minimization. Immune tolerance was defined by the absence of any immune event after minimization: absolute dd-cfDNA > 0.5%, relative change value (RCV) > 60% from baseline, biopsy-proven acute rejection (BPAR), or de novo donor-specific antibody (DSA). All other KTR were labeled intolerant. The primary endpoint was the rate of immune tolerance.

RESULTS: Immunosuppression was modified to tacrolimus and prednisone in 38 KTR at a median of 223 days post-transplant. Most KTR were older adults at low immunological risk: mean of 69 years and all had a calculated panel reactive antibody of 0%. 21 (55.3%) KTR met the primary end point of tolerance. The remaining 17 KTR were labeled intolerant secondary to dd-cfDNA elevations including absolute > 0.5% or RCV > 60% (n = 16 of 17, 94%), de novo DSA (n = 2 of 17, 11.8%), and/or BPAR (n = 4 of 17, 23.5%). Although not statistically significant, intolerant KTR were numerically more likely to have 5-6 HLA mismatches (82.5% vs. 52.4%, p = 0.31), less likely to have thymoglobulin induction (29.4% vs. 42.9%, p = 0.39), and were minimized earlier after transplant (196 vs. 256 days, p = 0.08) compared with tolerant KTR, respectively. Intervention after dd-cfDNA elevations included immunosuppression increase (50%), additional dd-cfDNA monitoring (81.3%), DSA testing (50%), and allograft biopsy (18.7%).

CONCLUSION: Approximately 50% of low immunological risk KTR with a baseline dd-cfDNA < 0.5% tolerated immunosuppression minimization to tacrolimus and prednisone without concerning dd-cfDNA elevations, BPAR, or DSA. Our study highlights the role of dd-cfDNA as part of the armamentarium for identifying minimization candidates and performing subsequent surveillance.

PMID:41568414 | DOI:10.1002/phar.70102

J Neurosurg Anesthesiol. 2026 Jan 22. doi: 10.1097/ANA.0000000000001086. Online ahead of print.

ABSTRACT

BACKGROUND: The association between intraoperative hypotension and delirium in patients with brain tumors remains unclear. We thus evaluated the association between intraoperative hypotension and postoperative delirium in patients recovering from neurological surgery.

METHODS: This was a secondary analysis of 3 prospective studies. Patients aged greater than 18 years who were scheduled for elective craniotomy for resection of glioma or frontotemporal lobe tumor were enrolled. Intraoperative hypotension was quantified through 3 metrics: mean arterial pressure area under the curve, time-weighted mean arterial pressure, and cumulative duration of hypotension. Our primary outcome was the association between hypotension and postoperative delirium.

RESULTS: The study comprised 738 patients (median age 56 y; 50% male) undergoing craniotomy for brain tumor resection. Postoperative delirium occurred in 29.0% (95% CI: 25.7%-32.3%) of patients. No statistically significant associations between intraoperative hypotension (absolute mean arterial pressure 60 to 75 mm Hg, relative reductions 10% to 40% from baseline) and postoperative delirium. However, the presence of preoperative tumor midline shift was an independent risk factor for postoperative delirium (adjusted odds ratio: 1.56, 95% CI: 1.09-2.22, P=0.014), and interacted with time-weighted average mean arterial pressure at relative reductions 10% based on the subgroup analysis.

CONCLUSIONS: In adult patients undergoing elective craniotomy for tumor resection, no significant association is found between intraoperative hypotension and postoperative delirium.

PMID:41568401 | DOI:10.1097/ANA.0000000000001086

Stat Med. 2026 Jan;45(1-2):e70369. doi: 10.1002/sim.70369.

ABSTRACT

The objective of this study is to perform variable selection and parameter estimation for analyzing partly interval-censored data based on a proportional hazards model that incorporates spatial effects. To broaden the model’s applicability across diverse scenarios, we consider two types of spatial structures: adjacency and distance information. Leveraging the differentiable properties of the $l_1$ -ball prior developed through projection-based methods, we have devised an efficient Bayesian algorithm by introducing latent variables and applying stochastic gradient Langevin dynamics principles. This algorithm can rapidly deliver results without resorting to complex sampling steps. Through simulations encompassing various scenarios, we have validated the performance of this method in both variable selection and parameter estimation. In our real data application, the proposed approach selects important variables associated with the emergence time of permanent teeth. Additionally, it identifies the spatial structure that best fits these data characteristics. This selection and identification are based on two Bayesian model selection criteria: the log pseudo-marginal likelihood and the deviance information criterion.

PMID:41568399 | DOI:10.1002/sim.70369

Biomater Investig Dent. 2026 Jan 15;13:45038. doi: 10.2340/biid.v13.45038. eCollection 2026.

ABSTRACT

AIM: The present study aimed to evaluate and compare the sealing ability of Biodentine, zirconia reinforced glass ionomer cement (GIC), and Mineral Trioxide Aggregate (MTA) as furcation repair materials.

MATERIALS AND METHODS: A total of 50 extracted permanent maxillary molars were collected and divided into three experimental groups and one control group. Group I – Biodentine (n = 15), Group II – zirconia reinforced GIC (n = 15), Group III – MTA Angelus (n = 15), and unrepaired, control group (n = 5). Crowns of teeth in experimental groups were sectioned 3 mm above the cementoenamel junction and roots 3 mm below the furcation. Standardised endodontic access openings were prepared, canal orifices and root ends were sealed with sticky wax. After coating with nail varnish, a 1 mm furcation perforation was created at a standardised location using a round carbide bur. Samples were flushed, dried, and incubated at 37°C for 24 h to simulate clinical conditions. All samples were subjected to orthograde and retrograde methylene blue dye challenge followed by dye extraction with a concentration of 65% nitric acid. Samples were then analysed using 550 ultraviolet-visible spectrophotometers.

STATISTICAL ANALYSIS: The results were analysed statistically by one-way analysis of variance (ANOVA) and Tukey’s multiple comparison tests.

RESULT: No statistically significant difference in sealing ability was observed between Biodentine, zirconia reinforced GIC, and MTA when used as a furcation perforation repair material.

CONCLUSION: Within the limitations of this study, it can be concluded that Biodentine, zirconia reinforced GIC, and MTA showed sealing ability comparable to each other.

PMID:41568394 | PMC:PMC12817067 | DOI:10.2340/biid.v13.45038

Front Oncol. 2026 Jan 6;15:1618237. doi: 10.3389/fonc.2025.1618237. eCollection 2025.

ABSTRACT

OBJECTIVES: This study aimed to investigate human epidermal growth factor receptor 2 (HER2) protein expression and gene amplification status in uterine serous carcinoma (USC) and ovarian high-grade serous carcinoma (HGSC), determine the frequencies of HER2 overexpression/amplification and HER2-low expression, evaluate two current HER2 interpretation criteria, and analyze the relationship between HER2 status and patient prognosis.

METHODS: A total of 51 patients with USC (including eight cases of mixed endometrial adenocarcinoma with predominant serous carcinoma components) and 165 patients with ovarian HGSC (including 43 patients who received neoadjuvant chemotherapy) were retrospectively recruited from the Department of Pathology, Peking University People’s Hospital between January 2019 and January 2025. Clinical and pathological characteristics were summarized. HER2 protein expression in whole-tissue sections was assessed using immunohistochemistry (IHC). HER2 scoring was performed according to two criteria: the 2023 American Society of Clinical Oncology/College of American Pathologists HER2 Testing Guidelines in Breast Cancer and the HER2 Immunohistochemistry Scoring System for Endometrial Serous Carcinoma proposed by the International Society of Gynecological Pathologists (ISGyP). Fluorescence in situ hybridization (FISH) was subsequently performed on cases with IHC scores of 1+, 2+, or 3+ for validation. Survival analysis was conducted based on HER2 status.

RESULTS: HER2 gene amplification was detected in 15/51 (29.4%) tissues from patients with USC (including mixed carcinomas with predominant serous morphology). HER2 amplification was identified in 6/122 (4.9%) tissues from patients with primary ovarian HGSC without prior chemotherapy, and in 3/43 (7.0%) tissues from patients with ovarian HGSC with residual disease after neoadjuvant chemotherapy. Evaluation of HER2 IHC results using both interpretation criteria revealed no difference in HER2 3+ expression rates for both USC and ovarian HGSC. However, differences existed in the classification of HER2-low expression (defined as IHC 2+ with negative FISH or IHC 1+). The ISGyP criteria identified more cases with low HER2 expression. For patients with USC, HER2 positivity was not statistically significantly associated with overall survival (OS) or progression-free survival (PFS), although it showed a trend toward higher recurrence. In terms of prognosis, for patients with ovarian HGSC group, HER2 positivity was associated with worse OS (p = 0.049). Among patients with ovarian HGSC after neoadjuvant chemotherapy, HER2 positivity was a strong predictor for shorter PFS (p = 0.003).

CONCLUSION: A certain proportion of USC and ovarian HGSC cases exhibit HER2 positivity and HER2-low expression. Different interpretation criteria lead to variations in the assessment of HER2 IHC results. The ISGyP criteria can identify more cases with low HER2 expression. Moreover, our findings suggest that HER2 status could be a relevant prognostic marker in these malignancies. Traditional anti-HER2 targeted therapies are indicated for HER2-positive patients, while a broader population of patients with HER2-low expression may benefit from novel anti-HER2 antibody-drug conjugates.

PMID:41568388 | PMC:PMC12815748 | DOI:10.3389/fonc.2025.1618237

Front Oncol. 2026 Jan 6;15:1552813. doi: 10.3389/fonc.2025.1552813. eCollection 2025.

ABSTRACT

PURPOSE: This study dosimetrically compares hypofractionated VMAT plans using the updated ESTRO-ACROP guidelines versus conventional delineation in patients undergoing immediate implant-based breast reconstruction after mastectomy.

METHODS: We retrospectively enrolled 22 patients with immediate implant-based reconstruction post-mastectomy (12 left-sided, 10 right-sided), treated between January 2022 and June 2025. All patients underwent CT simulation; those with left-sided cancer were positioned using deep inspiration breath-hold (DIBH), and those with right-sided cancer under free breathing. For each patient, conventional (C-TVD) and ESTRO-ACROP guideline-based (E-TVD) target volumes were independently delineated on the same CT dataset. Hypofractionated VMAT plans were designed using a 6-MV beam, single-isocenter, dual-arc technique, prescribing 40.05 Gy in 15 fractions to the planning target volume (PTV). All plans were normalized to ensure ≥95% PTV coverage by the prescribed dose. Dose-volume parameters for targets and organs at risk (OARs) were then compared between the two delineation approaches.

RESULTS: The conformity index (CI) of E-TVD was inferior to that of C-TVD; however, E-TVD achieved superior 95% prescription dose coverage of the target volume. Compared with C-TVD, E-TVD resulted in significantly lower V₂₀ and D_mean to the ipsilateral lung, with differences reaching statistical significance (P < 0.05). For the heart, E-TVD was associated with significantly lower V₂₀, as well as lower D_max and D_mean to the left anterior descending coronary artery (LAD), with all differences reaching statistical significance (P < 0.05). Subgroup analyses stratified by left versus right breast cancer revealed that in left breast cancer patients, E-TVD resulted in statistically significant reductions in ipsilateral lung V₂₀, V₁₀, and D_mean; bilateral lung V₂₀; heart V₂₀; LAD D_max and D_mean; and contralateral breast D_mean (all P < 0.05). In right breast cancer patients, E-TVD was associated with significantly lower ipsilateral lung D_mean and contralateral breast D_mean (both P < 0.05).

CONCLUSIONS: In patients with breast cancer who undergo total mastectomy followed by immediate implant-based breast reconstruction, the E-TVD approach confers superior protection to organs at risk.

PMID:41568383 | PMC:PMC12815867 | DOI:10.3389/fonc.2025.1552813

Front Oncol. 2026 Jan 6;15:1718288. doi: 10.3389/fonc.2025.1718288. eCollection 2025.

ABSTRACT

BACKGROUND: Systemic inflammation and immune dysregulation are recognized as key determinants of cancer progression and survival. The pan-immune-inflammation value (PIV), a hematologic-based composite biomarker, may reflect the host’s immune-inflammatory status. Its prognostic significance in brain metastases (BM), however, remains undefined.

METHODS: In a single-center retrospective cohort, 3,856 consecutive patients with radiologically confirmed BM diagnosed between 2013 and 2021 were included. PIV was calculated as neutrophil count × platelet count × monocyte count, divided by lymphocyte count. All blood cell counts were recorded in units of 10^9 cells per liter. Complete blood counts were taken within 7 days before the start of treatment. The optimal PIV cut-off, derived using maximally selected log-rank statistics, defined low and high PIV groups. OS was analyzed using multivariable Cox models adjusted for age, performance status, number of BM and extracranial metastases. A PIV-augmented GPA nomogram was developed and internally validated with bootstrap resampling. Time-dependent concordance indices, calibration and integrated discrimination improvement (IDI) were used to assess model performance. Subgroup and sensitivity analyses examined robustness across systemic and local treatment modalities, primary tumor types, sex and alternative PIV parameterizations.

RESULTS: The PIV cut-off separated 1,570 patients with low PIV and 2,286 with high PIV. High PIV was associated with worse OS and remained independently prognostic (hazard ratio 1.40; 95% confidence interval 1.29-1.52; p < 0.001), with consistent effects across treatment modalities, primary tumor types and sex. Alternative cut-offs and modeling PIV as a continuous variable (per 1-standard-deviation increase) produced effect estimates similar to the primary analysis. Adding PIV to the GPA modestly improved discrimination and increased IDI by 0.010 (95% confidence interval 0.006-0.015; p < 0.001); the PIV+GPA nomogram showed good 1-year calibration.

CONCLUSIONS: PIV is an independent prognostic factor for OS in BM patients. Incorporating this marker into the Graded Prognostic Assessment modestly improves risk stratification and supports an accessible nomogram for individualized survival prediction. External prospective validation, including longitudinal assessment of the pan-immune-inflammation value and integration with molecular and imaging markers, is needed before routine clinical implementation.

PMID:41568367 | PMC:PMC12815847 | DOI:10.3389/fonc.2025.1718288

Front Psychiatry. 2026 Jan 6;16:1721514. doi: 10.3389/fpsyt.2025.1721514. eCollection 2025.

ABSTRACT

OBJECTIVE: This study investigated how personality (Temperament, Character) influences the occurrence and onset age of Bipolar Disorder (BD). Unlike previous studies, Temperament and Character Inventory (TCI) dimensions as well as profiles were examined regarding BD onset age.

METHODS: We recruited within 5 years 179 adults with prevalent BD (37.4% males, mean age 48.0 ± 12.0 years) attending a general hospital outpatient clinic, in euthymia during the previous 3 months, and 96 controls (36.5% males, mean age 40.4 ± 12.6 years), a convenience sample of community adults recruited via snowball sampling. All participants completed TCI-140. Associations of personality with diagnosis were investigated using logistic regressions while case-only linear and Cox regressions examined associations of personality with onset age. Analyses included TCI dimensions, continuous and binary (dichotomized utilizing Greek general population medians), and profiles (all possible combinations of Temperament or Character high/low binary dimensions), adjusting for potential confounders.

RESULTS: In logistic regressions, BD risk was associated with higher scores in Novelty Seeking (NS), Harm Avoidance (HA) and Self-Transcendence (ST) and lower in Self-Directedness (SD) and Cooperativeness (CO). In linear and Cox regressions, high NS indicated earlier onset compared to low (B=-4.70 [-8.10, -1.30]; HR = 1.60 [1.15, 2.22]), while high SD indicated delayed onset (B = 5.24 [1.87, 8.62]; HR = 0.57 [0.40, 0.79]). In exploratory profile analyses, Narcissistic (high NS, HA and Reward Dependence [RD]) and Histrionic (high NS, low HA, high RD) Temperament profiles and Cyclothymic (low SD, high CO, high ST) and Melancholic (low SD, CO and ST) Character profiles were associated with earlier BD onset, while the Reliable (low NS, low HA, high RD) Temperament profile and Bossy (high SD, low CO, low ST), Creative (high SD, CO and ST) and Organized (high SD, high CO, low ST) Character profiles were associated with delayed onset. These associations, however, lost statistical significance after correcting for multiple comparisons and should be interpreted cautiously.

CONCLUSION: This study reaffirmed previous associations of TCI dimensions with BD risk, with two (NS, SD) also significantly relating for the first time to onset age. TCI profiles tentatively provided a more nuanced understanding of BD’s onset than dimensions but warrant further investigation in larger samples.

PMID:41568281 | PMC:PMC12815727 | DOI:10.3389/fpsyt.2025.1721514

J Orthop Surg Res. 2026 Jan 21. doi: 10.1186/s13018-025-06630-1. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the functional and radiographic outcomes of full arthroscopic subtalar joint arthroscopy combined with a calcaneal distractor for the management of Sanders type II and III calcaneal fractures.

METHODS: A retrospective analysis was conducted on 26 patients (26 feet) with Sanders type II and III calcaneal fractures who underwent treatment utilizing a full arthroscopic subtalar arthroscopy technique combined with a calcaneal distractor. The surgeries were performed in the Department of Orthopedics at Xuzhou Central Hospital between January 2019 and December 2022. The cohort included 20 males and 6 females, with a mean age of 47.96 ± 8.87 years (range: 34-66 years). According to the Sanders classification, 7 fractures were type II and 19 were type III. Preoperative assessments yielded the following scores: a mean Visual Analogue Scale (VAS) score for pain of 7.35 ± 1.06 points (range: 4-9), a mean American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score of 52.27 ± 9.52 points (range: 55-85), and a mean SF-36 quality of life score of 92.04 ± 4.88 points (range: 80-100).All patients underwent fixation via the combined subtalar joint arthroscopy and calcaneal distractor approach. Postoperative evaluations focused on wound healing status, quality of fracture reduction, and evidence of bony union. Functional outcomes and pain levels were assessed using the VAS, AOFAS ankle-hindfoot score, and the SF-36 questionnaire. A comparison of preoperative and final follow-up scores was performed using the independent samples t-test.

RESULTS: All procedures were successfully completed without intraoperative complications. The mean operative time was 69.7 ± 10.4 min (range: 40-110). All surgical incisions achieved primary healing, with no instances of soft tissue infection, necrosis, or sensory disturbances observed during the postoperative period. Postoperative radiographic measurements of the calcaneus, including its length, width, height, Böhler’s angle, and Gissane’s angle, demonstrated significant improvement compared to preoperative values (all P < 0.01). Furthermore, no statistically significant differences were observed in these parameters between the immediate postoperative period and the final follow-up (all P > 0.05), indicating well-maintained fracture reduction and satisfactory healing. The patients showed significant improvement in the VAS, AOFAS, and SF-36 scores postoperatively compared to their preoperative status (all P < 0.01). At the final follow-up, functional outcomes were satisfactory. According to the AOFAS ankle-hindfoot scale, the scores were graded as excellent in 24 cases and good in 2 cases, yielding an excellent-good rate of 100.0%.

CONCLUSION: The combined technique of full arthroscopic subtalar arthroscopy and a calcaneal distractor demonstrates high precision in fracture reduction and satisfactory clinical outcomes, establishing it as a reliable and effective method for managing Sanders type II and III calcaneal fractures.

PMID:41566367 | DOI:10.1186/s13018-025-06630-1

J Health Popul Nutr. 2026 Jan 21. doi: 10.1186/s41043-026-01239-4. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to analyze trends in colorectal cancer (CRC) burden attributable to lifestyle factors in China (1990-2021), focusing on shifts of lifestyle, and to project future trajectories to inform public health strategies.

METHODS: Data from the Global Burden of Disease Study 2021 were utilized to assess deaths, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) for CRC linked to nine lifestyle factors (including: diet low in whole grains, diet low in milk, diet low in fiber, diet low in calcium, diet high in red meat, diet high in processed meat, smoking, high alcohol use, and high BMI). Statistical analyses included estimated annual percentage change (EAPC), Joinpoint regression, age-period-cohort modeling, and Autoregressive Integrated Moving Average (ARIMA) projections (2022-2050).

RESULTS: Between 1990 and 2021, the burden of CRC attributable to most dietary factors declined, with significant reductions in low fiber (DALYs EAPC: -3.77) and low calcium intake (DALYs EAPC: -3.18). In contrast, processed meat intake showed an increase (DALYs EAPC: 1.64). Alcohol-related CRC burden rose slightly (DALYs EAPC: 0.35), while high BMI showed a marked increase (DALYs EAPC: 2.31). ARIMA projections suggest continued declines in dietary risk-related CRC burden. In contrast, the burden attributable to high body-mass index (BMI) is projected to rise substantially through 2050.

CONCLUSIONS: While improved dietary habits have reduced CRC burden in China, rising obesity pose growing threats. Public health policies must prioritize interventions targeting processed meat intake, and weight management to curb future CRC incidence and mortality.

PMID:41566355 | DOI:10.1186/s41043-026-01239-4