Nevin Manimala

Front Pharmacol. 2025 Nov 19;16:1619920. doi: 10.3389/fphar.2025.1619920. eCollection 2025.

ABSTRACT

BACKGROUND: Sufentanil-induced cough (SIC) is prevalent in anesthesia practice. A variety of interventions have been employed to prevent SIC. However, the optimal intervention remains elusive.

METHODS: A comprehensive search of the literature was conducted on the PubMed, Embase, Web of Science, Cochrane Library (CENTRAL) and China National Knowledge Infrastructure (CNKI) databases. The search was limited to publications prior to July 5, 2025. A network meta-analysis (NMA) was conducted using the R software. A Bayesian framework was employed for this NMA. Comparisons of competing models based on the deviance information criterion (DIC) were used to select the optimal model for NMA. The primary outcome is the overall incidence of SIC. The secondary outcomes included the incidence of mild SIC and moderate to severe SIC.

RESULTS: The NMA included 37 randomized controlled trials (RCTs) with 5,105 patients and 18 interventions. Pairwise meta-analysis results indicate that the intervention group significantly decreases the overall incidence of SIC (7.6% vs. 34.8%; OR 0.13; 95% CI 0.09 to 0.18; P < 0.0001; I² = 53.0%), the incidence of mild SIC (4.0% vs. 13.0%; OR 0.28; 95% CI 0.22 to 0.35; P = 0.369; I² = 5.7%), and the incidence of moderate to severe SIC (3.4% vs. 21.7%; OR 0.13; 95% CI 0.10 to 0.16; P = 0.040; I² = 30.6%). NMA results suggested that nalbuphine, dezocine, and butorphanol significantly reduced the overall incidence of SIC, as well as the incidence of mild and moderate-to-severe SIC. Additionally, remifentanil and esketamine were effective in reducing both the overall incidence of SIC and the incidence of moderate to severe SIC. The use of a mechanical dropper was also effective in reducing the incidence of moderate to severe SIC.

CONCLUSION: Three pharmacological interventions-nalbuphine, dezocine, and butorphanol significantly reduced the overall incidence of SIC, as well as the incidence of mild and moderate-to-severe SIC. Additionally, remifentanil and esketamine were effective in reducing the overall incidence of SIC and the incidence of moderate to severe SIC. The application of a mechanical dropper was also effective in reducing the incidence of moderate to severe SIC. The remaining interventions indicated a trend toward reducing SIC incidence; however, this was not statistically significant.

SYSTEMATIC REVIEW: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024581866 , PROSPERO (CRD42024581866).

PMID:41347178 | PMC:PMC12673273 | DOI:10.3389/fphar.2025.1619920

Front Pharmacol. 2025 Nov 19;16:1707223. doi: 10.3389/fphar.2025.1707223. eCollection 2025.

ABSTRACT

INTRODUCTION: This study aimed to characterize time-dependent metabolic alterations and identify metabolites associated with treatment response in HER2-negative breast cancer patients undergoing neoadjuvant chemotherapy (NAC) with the TEC regimen (docetaxel, epirubicin, and cyclophosphamide).

METHODS: A total of 60 plasma samples were collected from 20 patients at three time points: baseline (T1), after three cycles of NAC (T2), and before surgery (T3). Pathological assessment classified patients into three response groups: pathologic complete response (pCR, n = 5), pathologic partial response (pPR, n = 7), and pathologic stable disease (pSD, n = 8).

RESULTS: After three cycles of NAC, a greater decrease in glycochenodeoxycholate was associated with poorer treatment response, whereas a larger reduction in LysoPC(18:1) correlated with better response. Following six cycles, elevated epinephrine levels were positively associated with therapeutic efficacy, while increased cysteine levels were linked to unfavorable outcomes. Ursodeoxycholic acid showed an upward trend in pCR patients but declined in pPR and pSD groups. Combined analysis of ursodeoxycholic acid and cysteine improved the predictive performance for treatment response.

DISCUSSION: These findings reveal dynamic metabolic reprogramming during NAC and suggest that ursodeoxycholic acid and cysteine may serve as potential predictive biomarkers of therapeutic efficacy in HER2-negative breast cancer patients treated with the TEC regimen.

PMID:41347169 | PMC:PMC12673219 | DOI:10.3389/fphar.2025.1707223

Front Pharmacol. 2025 Nov 19;16:1694163. doi: 10.3389/fphar.2025.1694163. eCollection 2025.

ABSTRACT

INTRODUCTION: Antithrombotic management in Chronic Kidney Disease (CKD) is a clinical dilemma. This study aimed to empirically evaluate the “de facto interchangeability” of the antiplatelet indobufen and the anticoagulant rivaroxaban by comparing their real-world effectiveness and safety in hospitalized CKD patients.

METHODS: In this retrospective cohort study (2020-2024), we analyzed CKD patients treated with indobufen or rivaroxaban. A multi-stage analysis first used machine learning to assess baseline cohort comparability, overcoming limitations of p-value-based tests. Subsequently, a Linear Mixed Model (LMM), adjusted for confounders including polypharmacy, assessed independent drug effects on in-hospital thrombosis, hemorrhage, and longitudinal laboratory markers.

RESULTS: Machine learning demonstrated the clinical comparability of the indobufen and rivaroxaban cohorts. The incidence of in-hospital thrombosis was numerically lower in the indobufen group (3.65% vs. 7.58%; P = 0.101), while hemorrhage rates were similar (2.19% vs. 2.27%; P = 1). The LMM analysis, beyond verifying indobfen’s expected antiplatelet activity (modulating MPV, PDW), revealed pleiotropic effects (increased prealbumin, HDL-C) and a significant reduction in urine occult blood (P < 0.001), suggesting renal safety. Notably, the model demonstrated that apparent effects on hemoglobin and eGFR were attributable to confounding by co-medications, not a direct drug effect.

CONCLUSION: In this real-world CKD cohort, indobufen and rivaroxaban demonstrated comparable clinical effectiveness and safety. Combining machine learning with longitudinal models helps to statistically adjust for complex confounders like polypharmacy, thereby providing a more robust estimate of a drug’s independent effect.

PMID:41347166 | PMC:PMC12672237 | DOI:10.3389/fphar.2025.1694163

Front Pharmacol. 2025 Nov 19;16:1612508. doi: 10.3389/fphar.2025.1612508. eCollection 2025.

ABSTRACT

OBJECTIVE: The purpose is to evaluate the clinical efficacy and safety of Qianyang Yuyin Granules in the treatment of vascular damage in essential hypertension systematically.

METHODS: Relevant literature databases include CNKI, Wanfang Data, VIP, CBM, PubMed, Web of Science, Cochrane Library. DeepSeek-V3 was used for AI-assisted retrieval. The time limit for searching was from the establishment of the database to 15 April 2025. Eligible randomized controlled clinical trials were screened according to inclusion and exclusion criteria. Publication bias assessment and quality evaluations were analysed by using the Cochrane Handbook and meta-analysis was performed by using RevMan 5.3 software. Finally, using Trial Sequential Analysis 0.9Beta software to perform the trial sequential analysis.

RESULTS: 21 studies were finally included, with a total sample of 1,419 cases, 728 cases in the experimental group and 691 cases in the control group. Meta-analysis suggested that the trial group using Qianyang Yuyin Granules was effective in lowering PWV-BS [MD = -0.58, 95%CI: (-0.88, -0.29), P < 0.0001], PWV-ES [MD = -0.79, 95%CI: (-1.22, -0.36), P = 0.0003] in the elderly population with essential hypertension (≥60 years old), lowering inflammatory factor-related indexes including CRP [SMD = -0.37, 95%CI: (-0.58, -0.16), P = 0.0005] and TNF-α [SMD = -0.44, 95%CI: (-0.70, -0.18), P = 0.001], lowering systolic blood pressure [MD = -3.86, 95%CI: (-5.33, -2.39), P < 0.00001] and diastolic blood pressure [MD = -2.24, 95%CI: (-3.39, -1.10), P = 0.0001] were all superior to the control group that only used basic treatment and the differences were statistically significant; The incidence rate of adverse reactions in the experimental group was not statistically significant when compared with that of the control group [OR = 0.71, 95%CI: (0.26, 1.93), P = 0.51]. The sequential analysis further suggested that the addition of Qianyang Yuyin Granules to reduce PWV and CRP in peripheral blood had a precise role.

CONCLUSION: The addition of Qianyang Yuyin Granules in the treatment of vascular damage in mild-to-moderate essential hypertension can improve the clinical efficacy without increasing the adverse effects of conventional drugs, and has further clinical application value. However, further research with larger scale and stricter quality control is needed.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42025641482.

PMID:41347150 | PMC:PMC12672466 | DOI:10.3389/fphar.2025.1612508

Front Endocrinol (Lausanne). 2025 Nov 19;16:1689238. doi: 10.3389/fendo.2025.1689238. eCollection 2025.

ABSTRACT

INTRODUCTION: Acute decompensated heart failure (ADHF), a critical cardiovascular emergency, is driven by a metabolic and inflammatory imbalance that serves as the central mechanism of disease progression. This study aims to analyze the heterogeneity of mortality risk in patients with comorbid diabetes mellitus (DM) and HF using the C-reactive protein-triglyceride-glucose index (CTI).

METHODS: This study evaluated 1,051 ADHF patients from the Jiangxi-ADHF II cohort. The Boruta algorithm, a fully automated feature selection method, was applied to identify key predictive variables and rank their importance. Cox proportional hazard models were constructed to assess the association between the CTI and 30-day mortality risk in ADHF patients, stratified by DM status. To further elucidate the nonlinear characteristics of risk associations, restricted cubic splines were employed to construct dose-response relationship curves. Additionally, heatmaps were used to assess the joint association of CTI components with mortality risk.

RESULTS: The 30-day follow-up revealed a mortality rate of 8.3%. Through the Boruta algorithm and multivariate Cox regression analysis, we identified CTI as a key prognostic factor for short-term mortality risk in ADHF patients, especially in those with comorbid DM. The restricted cubic splines model further confirmed the linear and non-linear associations between CTI and mortality in ADHF patients with and without DM. Additionally, heatmaps visualized the association between CTI components and mortality: to summarize, the mortality risk is relatively low when the triglyceride-glucose index remains within specific ranges (8.25-9.0 for patients with DM; 7.0-9.0 for non-DM patients) and the C-reactive protein level is maintained below 50 mg/L. Further subgroup analyses highlighted distinct risk modulation patterns: non-DM ADHF patients exhibited mortality risk heterogeneity across gender, hypertension, and stroke subgroups; however, the DM comorbid group demonstrated uniform risk profiles with no statistically significant differences.

DISCUSSION: This study demonstrates the clinical utility of the novel inflammatory-metabolic index CTI in mortality risk assessment for ADHF patients, with superior risk stratification efficacy observed in those with DM comorbidity.

PMID:41347140 | PMC:PMC12672285 | DOI:10.3389/fendo.2025.1689238

Depress Anxiety. 2025 Nov 26;2025:4470169. doi: 10.1155/da/4470169. eCollection 2025.

ABSTRACT

BACKGROUND: Major depressive disorder (MDD) is common and associated with high social and economic burden. Knowledge of characteristics of hospitalized adults with MDD can help identify clinical treatment and prevention targets.

METHODS: The multicenter “Patient Characteristics, Validity of Clinical Diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression” (OASIS-D) study assessed characteristics of patients aged 18-75 years hospitalized between October 2020 and December 2024, who were admitted to a psychiatric inpatient unit for MDD at eight German centers. Baseline illness-, treatment-, and suicidality-related characteristics of the overall sample are reported.

RESULTS: Among 3795 patients (median age = 42.0, interquartile range [IQR] = 27.5-57.0 years; females = 53.9%) with MDD (severe episode = 75.3%, psychotic features = 7.9%; first episode = 34.9%; treatment-resistant depression [TRD] = 18.2%). Psychiatric comorbidities of MDD were present in 46.2% and included substance use disorder (18.9%), personality disorders (8.4%), stress/adjustment disorders (7.6%), and phobic/other anxiety disorders (6.6%). In 42.5%, the admission was prompted by a psychiatric emergency, primarily due to suicidality (35.0%), followed by stupor/refusal/intoxication/acute agitation (0.9%-1.5%), or danger to others/delirium (0.1%-0.3%). Overall, 72.0% of patients had active or passive suicidal thoughts, and 11.5% had attempted suicide within 2 weeks prior to admission. Furthermore, 83.9% had lifetime suicidal thoughts, and 36.0% had lifetime suicide attempts. Altogether, 76.8% had received outpatient psychiatric care within their lifetime (62.3% within 6 months), and 57.8% of patients had lifetime inpatient treatment for MDD. At admission, 71.6% of patients were prescribed psychiatric medications: antidepressants = 59.8%; antipsychotic = 25.1%, anxiolytics/hypnotics = 11.8%, and mood stabilizers = 8.6%. Additionally, 4.0% had previously received electroconvulsive therapy (ECT). The median hospitalization duration was 31.0 (IQR = 13.0, 57.0) days.

CONCLUSION: Almost half of admissions in adults with MDD were considered emergencies, with 90% being related to suicidality, and only <60% received antidepressants at admission. These data underscore the need for early identification and treatment of adults with MDD, especially those with suicidality. Outcomes of this population required further study. Trial Registration: ClinicalTrials.gov identifier: NCT04404309.

PMID:41347111 | PMC:PMC12674865 | DOI:10.1155/da/4470169

BMC Urol. 2025 Dec 4. doi: 10.1186/s12894-025-02011-2. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to evaluate the ability of the systemic immune-inflammation index (SII), which is tested before transrectal ultrasound-guided systematic prostate biopsy, to predict the histopathology of non-malignant and malignant prostate tissue.

METHODS: Data from 1040 patients who underwent transrectal ultrasound-guided prostate biopsy between June 2019 and January 2023 due to high prostate-specific antigen levels or palpation of suspicious prostate cancer nodules via digital rectal examination were analyzed retrospectively. The patients were divided into two groups as biopsy negative and prostate cancer. The SII, platelet/lymphocyte ratio (PLR), and neutrophil/lymphocyte ratio (NLR) were compared between the two groups. Statistical analyses were performed using Student’s t, Mann-Whitney U, and one-way ANOVA tests, along with ROC curve analysis and DeLong’s test to assess diagnostic performance.

RESULTS: There was no difference between the groups in terms of the SII, PLR, or NLR (p > 0.05). When evaluated according to the European Urology Association risk groups for biochemical recurrence of localized and locally advanced prostate cancer based on systematic biopsy, a significant difference was observed in the SII and PLR markers between the groups with biopsy negative and those with high-risk prostate cancer (p = 0.009, and p < 0.001, respectively). In the ROC analysis, the AUC for the SII was 0.568 (95% CI 0.523-0.628). The best limit value was determined to be 591.4, and for values ≥ 591.4, the sensitivity was determined to be 0.5, and the specificity was 0.571. For the PLR, the AUC was 0.618 (95% CI 0.559-0.676). The best limit value was 139.6, and for values ≥ 139.6, the sensitivity was 0.52, and the specificity was 0.72.

CONCLUSIONS: Hematological inflammatory parameters before prostate biopsy are not effective markers for distinguishing between biopsy negative and malignant pathologies. The inflammatory markers SII and PLR can be used as diagnostic tools in high-risk prostate cancer patients but cannot be used as markers for the detection of pathologies in low- and intermediate-risk patients.

PMID:41345845 | DOI:10.1186/s12894-025-02011-2

Med Phys. 2025 Dec;52(12):e70183. doi: 10.1002/mp.70183.

ABSTRACT

BACKGROUND: Compared to photon therapy (XT), proton therapy (PT) can often reduce normal tissue toxicity for head and neck (HN) cancer patients, despite being a limited resource. On the other hand, clinical decision-making process to select between PT and XT (e.g., treatment planning and then plan evaluation for comparing normal tissue complication probabilities (NTCP) between XT and PT) is time-consuming and resource demanding.

PURPOSE: This study aims to develop and validate the feasibility of an artificial intelligence (AI)-based automated method for efficient patient selection between PT and XT.

METHODS: A heterogeneous cohort of 104 bilateral HN patients with auto-planned PT and XT plans was analyzed, covering diverse tumor subsites and prescription dose levels. To ensure accurate dose and NTCP prediction, a joint-modality prediction framework was developed, incorporating a 3D attention-gated U-net with a multi-constrained loss function. A stratified 10-fold cross-validation strategy was employed to evaluate and compare model performance. The NTCP differences between XT and PT for grade II/III xerostomia/dysphagia exceeding certain thresholds are used to select patients for PT according to the Landelijk Indicatie Protocol Protonentherapie (versie 2.2) (LIPPv2.2).

RESULTS: AI-assisted patient selection process took about 10.1 s per patient. Our method achieved an accuracy of 85.58% and a weighted accuracy of 81.11% in patient selection. For dysphagia grades ≥ 2 and ≥ 3, the predicted results exhibited consistent selection with the ground truth in 86.54% and 89.42% of cases, respectively. Compared to previous models, the average ΔNTCP prediction error (ΔNTCP ground truth-ΔNTCP predicted, mean ± SD) of the proposed method was 1.47 ± 1.80%, statistically lower than U-net (1.67 ± 2.20%) and hierarchically densely connected U-net (2.34 ± 3.25%). Moreover, the joint-modality prediction of PT and XT dose distributions using Attention U-net achieved comparable performance to separate single-modality predictions.

CONCLUSION: This study highlights the potential of a novel AI-assisted framework with joint-modality prediction to enhance efficiency and precision for proton-photon patient selection in the heterogeneous dataset, demonstrating the generalizability and robustness of the proposed approach.

PMID:41345820 | DOI:10.1002/mp.70183

Neurogastroenterol Motil. 2025 Dec 4:e70216. doi: 10.1111/nmo.70216. Online ahead of print.

ABSTRACT

BACKGROUND: The reference standard for the assessment of esophageal motility and sphincter function is high-resolution esophageal manometry (HRM). Diagnostic values for HRM are determined by the Chicago Classification (CC v4.0), which is based almost entirely on distal esophageal function without measures to address the proximal esophageal segment. Therefore, we sought to determine normal HRM values for proximal esophageal function when obtained in the standard HRM positions (supine and upright).

METHODS: Healthy, asymptomatic adults (≥ 18 years) were recruited. All participants completed a standard protocol. CC v4.0 measurements, along with a proximal contractile integral (PCI) (millimeters mercury-seconds-centimeters[mmHg-s-cm]), temporal measures of proximal and distal contractility (seconds), and lengths of proximal and distal esophagus (centimeters), were performed. Summary statistics, tests of normality, and paired two-sided t-tests were performed.

RESULTS: HRM data from 30 participants were included. Mean supine PCI was 423.9 mmHg-s-cm with a mean contraction time of 3.2 s and a mean length of 5.5 cm. The mean upright PCI was 183.9 mmHg-s-cm with a mean contraction time of 2.2 s, and a mean length of 4.5 cm. All proximal values were significantly different comparing the two positions (PCI p < 0.0001; time p < 0.0001; length p < 0.0001). All distal measurements fell within the ranges of normal, and all measures for contractile integral, contraction time, and contraction length were statistically significantly different (p < 0.0001 for all) comparing proximal versus distal measurements.

CONCLUSIONS: These preliminary data represent our first attempt to quantify normal proximal esophageal function using HRM measurements of contractile vigor, contraction length, and time.

PMID:41345798 | DOI:10.1111/nmo.70216

Magn Reson Med. 2025 Dec 4. doi: 10.1002/mrm.70212. Online ahead of print.

ABSTRACT

PURPOSE: Magnetic resonance elastography (MRE) of the heart has predominantly utilized breath-held acquisitions with limited anatomic coverage. This work investigates the feasibility of 3D, free-breathing cardiac MRE.

METHODS: A 3D hybrid radial and EPI acquisition is utilized and combined with retrospective binning of k-space via physiologic monitoring, iterative reconstruction, MRE processing and inversions, and post-processing specialized for cardiac imaging.

RESULTS: Feasibility of free-breathing stiffness mapping of the left ventricular myocardium was demonstrated in 11 participants. Myocardial stiffness estimates were obtained throughout the left ventricle for seven temporal states of the cardiac cycle. Stiffness estimates were presented in participant-specific images, 17-segment bullseye plots, and stiffness plots throughout the cardiac cycle. Results indicate increased stiffness in systolic states, with localized stiffness heterogeneity observed between participants, illustrating a key benefit of 3D cardiac MRE acquisition. Mean stiffness estimates obtained through 11 subjects were 4.44 ± 0.68 kPa (begin-systole), 5.74 ± 0.94, 5.42 ± 0.87 (end-systole), 3.84 ± 0.71 (begin-diastole), 3.51 ± 0.74, 3.54 ± 0.52, and 3.55 ± 0.59 kPa (end-diastole). Statistical testing indicated significant differences in stiffness across cardiac states with one-way, repeated-measures ANOVA (p < 0.001) and Friedman’s test (p < 0.001). Experiments in scanning three participants with and without applied motion indicated that stiffness changes were more robustly detected in systole than in diastole, although patterns were subject-specific. Comparison of free-breathing stiffness measurements against reference breath-held measurements yielded similar systolic stiffness estimates.

CONCLUSIONS: This study establishes the feasibility of free-breathing, 3D cardiac MRE in healthy volunteers. With the current framework, stiffness estimation appears more robust in systole, and the reliability of diastolic estimates is limited and subject-specific.

PMID:41345797 | DOI:10.1002/mrm.70212