Nevin Manimala

ADMET DMPK. 2026 Jul 26;14:3328. doi: 10.5599/admet.3328. eCollection 2026.

ABSTRACT

BACKGROUND AND PURPOSE: Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising cell-free therapy for osteoarthritis (OA). However, their transition into clinical therapeutics is constrained by unstandardized pharmacokinetics and heterogeneous preclinical reporting.

EXPERIMENTAL APPROACH: A meta-analysis of preclinical in vivo OA models evaluating MSC-EV therapy was conducted. Study quality was rigorously assessed using MISEV 2023 (Minimal Information for Studies of Extracellular Vesicles, 2023) criteria and the SYRCLE (Systematic Review Centre for Laboratory animal Experimentation) risk-of-bias tool. Quantitative synthesis was performed for the Osteoarthritis Research Society International (OARSI) histological score, reporting pooled mean differences (MDs) and 95 % confidence intervals (95% CIs), along with heterogeneity (I ² statistic) and microRNA (miRNA) cargo analysis.

KEY RESULTS: MSC-EV administration conferred robust structural protection against cartilage degradation. Quantitative synthesis of human-derived MSC-EVs (26 studies) significantly reduced OARSI scores (MD -3.27, 95% CI -4.66 to -1.88; p < 0.0001). Similarly, quantitative synthesis of animal-derived MSC-EVs (8 studies) demonstrated an even more profound effect (MD -5.58, 95% CI -7.13 to -4.03; p < 0.0001). Non-parametric Trim-and-Fill analysis estimated zero missing studies in both datasets, confirming that these effect sizes are highly robust to publication bias. Despite these robust efficacy signals, significant heterogeneity (I ² > 84 %) persisted. Meta-regression revealed that arbitrary dosage metrics, whether reported by particle count or protein concentration, failed to reliably predict treatment efficacy, highlighting severe gaps in dose-exposure standardization.

CONCLUSION: MSC-EVs demonstrate highly potent, cross-species efficacy in attenuating OA progression. However, clinical translation is critically bottlenecked by a lack of ADMET (absorption, distribution, metabolism, excretion and toxicity) compliance. Future research must prioritize standardized particle-based dosing, in vivo pharmacokinetic tracking, and rigorous cargo-function validation to enable regulatory approval.

PMID:42633484 | PMC:PMC13499667 | DOI:10.5599/admet.3328

Cureus. 2026 Jul 23;18(7):e113232. doi: 10.7759/cureus.113232. eCollection 2026 Jul.

ABSTRACT

Background Septic shock is a leading cause of mortality in intensive care units. Blood lactate is a key biomarker of tissue hypoperfusion; however, the prognostic value of a single initial lactate measurement remains debated. This study aimed to evaluate the predictive value of admission blood lactate levels for 28-day mortality in patients with septic shock. Methods A prospective, descriptive, and analytical pilot study was conducted, including 41 patients admitted for septic shock to a multidisciplinary intensive care unit in Rabat, Morocco, over a six-month period. Demographic, clinical, and biological data, including blood lactate levels at admission, were collected. The association between initial lactate and 28-day mortality was analyzed using non-parametric tests, receiver operating characteristic (ROC) curve analysis, and logistic regression. Results The mean age of patients was 60.9 years, with a male-to-female ratio of 1.27 (23 men (56.1%) and 18 women (43.9%)). The overall 28-day mortality rate was 56.1% (n = 23). Median admission lactate levels were higher in non-survivors (3.9 mmol/L; n = 23 (56.1%)) than in survivors (2.35 mmol/L; n = 18 (43.9%)), although this difference was not statistically significant (p = 0.231). The ROC curve showed poor discriminative performance (AUC = 0.610; p = 0.227). Logistic regression analysis did not identify admission lactate as an independent predictor of mortality. Conclusion Although higher lactate levels were observed in deceased patients, admission blood lactate alone demonstrated limited prognostic value for predicting 28-day mortality in this cohort of septic shock patients. Lactate interpretation should be dynamic and integrated into a comprehensive clinical assessment.

PMID:42633475 | PMC:PMC13499588 | DOI:10.7759/cureus.113232

Cureus. 2026 Jul 23;18(7):e113238. doi: 10.7759/cureus.113238. eCollection 2026 Jul.

ABSTRACT

BACKGROUND: Hypertension is a major non-communicable disease and a leading contributor to cardiovascular morbidity and mortality. Its burden is increasing in rural India due to rapid lifestyle and epidemiological transitions.

OBJECTIVES: This study aims to assess the prevalence of hypertension and its associated risk factors among adults in a rural community in Gwalior district.

METHODS: A community-based cross-sectional study was conducted from May 2023 to April 2024 among 360 adults selected through multistage sampling. Data were collected using a semi-structured questionnaire covering sociodemographic, dietary, and behavioral factors. Anthropometric measurements and blood pressure were recorded using standard procedures. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg or current antihypertensive treatment. Data were analyzed using descriptive statistics and the chi-square test.

RESULTS: Among 360 participants, 152 (42.2%) were aged 36-50 years and 180 (50.0%) were male. Hypertension was present in 139 (38.6%) participants, including stage 1 hypertension in 100 (27.8%) and stage 2 hypertension in 39 (10.8%). Pre-hypertension was observed in 106 (29.4%), while 115 (31.9%) had normal blood pressure. Overweight and obesity were found in 119 (33.1%) and 65 (18.1%) participants, respectively. Increased waist circumference and waist-to-hip ratio (WHR) were observed in 162 (45.0%) and 157 (43.6%) participants, respectively. Extra salt intake was reported by 212 (58.9%), smoking by 99 (27.5%), alcohol consumption by 106 (29.4%), and smokeless tobacco use by 120 (33.3%) participants. Significant associations were found between hypertension and male sex, overweight/obesity, excess salt intake, smoking, alcohol consumption, and family history of hypertension (p < 0.05).

CONCLUSION: Hypertension and pre-hypertension affected over two-thirds of the study population. Targeted screening, lifestyle modification, dietary interventions, and strengthened primary healthcare services are needed for early detection and prevention of hypertension.

PMID:42633473 | PMC:PMC13499593 | DOI:10.7759/cureus.113238

Cureus. 2026 Jul 23;18(7):e113233. doi: 10.7759/cureus.113233. eCollection 2026 Jul.

ABSTRACT

Introduction Although human milk provides unparalleled immunobiological and nutritional advantages essential for optimal neonatal development, the establishment of successful lactogenesis and sustained breastfeeding remains a complex psychophysiological challenge, particularly for primiparous mothers. First-time parturients frequently encounter biomechanical difficulties, such as suboptimal infant positioning and latch, which are compounded by postnatal anxiety. These factors can disrupt oxytocin-mediated milk let-down and precipitate disorganized neurobehavioral feeding reflexes in the newborn. Traditional postnatal lactation support is often reactive, administered during a period of high maternal fatigue and physiological stress. Therefore, structured antenatal lactation counseling emerges as a critical, proactive intervention designed to enhance maternal self-efficacy, provide anticipatory guidance, and mitigate the early introduction of prelacteal feeds. This randomized controlled trial (RCT) aimed to empirically validate this paradigm shift within a localized, high-volume clinical setting. It sought to investigate the effectiveness of targeted antenatal lactation counseling on both maternal breastfeeding practices and newborn feeding behaviors among primiparous mothers attending a tertiary care hospital in Puducherry, ultimately seeking to optimize perinatal care protocols through rigorous, evidence-based intervention. Methods An RCT was conducted with 130 primiparous women aged 18 to 35 years who had completed 32 weeks of gestation and delivered at term. A group counseling technique was used for the intervention group, wherein groups of five mothers received 30-minute antenatal lactation counseling sessions during antenatal visits. The lactation counseling on breastfeeding was repeated three times at 32, 34, and 36 weeks of gestation, while the control group received only routine care. Breastfeeding practices and newborn feeding behavior were assessed using a structured breastfeeding practices checklist and the Infant Breastfeeding Assessment Tool (IBFAT) on the second postnatal day. Results Baseline variables did not differ significantly between the groups. The intervention group showed significantly better breastfeeding practices (t = 5.384, p = 0.000) and newborn feeding behavior (t = 3.22, p = 0.02). Breast engorgement was lower in the intervention group, though the difference was not statistically significant. Conclusions Based on our findings, proper lactation counseling provided to primiparous mothers at each contact point during antenatal visits improves breastfeeding practices and promotes optimal newborn feeding behavior.

PMID:42633470 | PMC:PMC13499584 | DOI:10.7759/cureus.113233

J Health Econ Outcomes Res. 2026 Aug 20;13(2):87-93. doi: 10.36469/001c.164460. eCollection 2026.

ABSTRACT

BACKGROUND: The evolving obesity treatment landscape requires examining clinical and economic outcomes, but ICD-10-CM coding inconsistencies hinder patient identification in claims databases.

OBJECTIVES: This study aims to validate obesity diagnosis codes and identify factors influencing their utilization.

METHODS: This retrospective cohort study utilized claims and clinical data from the Healthcare Integrated Research Database (HIRD®) to identify adults with a BMI of 30 kg/m² or higher, spanning the period from June 2021 to October 2022. The study examined the use of ICD-10-CM diagnosis codes for obesity across two distinct timeframes: a 6-month period before and after the index date for prevalence and modeling purposes, and a 60-day window around the index date for validity calculations. For validation, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the ICD-10-CM codes were measured, classifying patients as true or false positives or negatives based on their BMI and coding presence. Multivariable logistic regression was used to identify factors predicting obesity coding, guided by clinical reasoning, statistical results, and refined through backward elimination regression.

RESULTS: Out of 2 218 115 patients with available BMI data during the relevant period, 966 427 (44%) had a BMI of 30 kg/m² or above. The study identified 380,606 true positives, 17 422 false positives, 1 234 266 true negatives, and 585 821 false negatives, resulting in a PPV of 95.6%, a NPV of 67.8%, a specificity of 98.6%, and a sensitivity of 39.4%. The prevalence of obesity coding was 54%. Increased likelihood of coding was associated with being female, over the age of 24, non-White, insured by Medicare Advantage, having lower socioeconomic status, higher BMI, and receiving weight management interventions.

CONCLUSION: ICD-10-CM codes demonstrate high specificity and PPV but low sensitivity, indicating that while coded cases are likely true obesity, many patients with obesity are not captured in claims.

PMID:42633467 | PMC:PMC13499625 | DOI:10.36469/001c.164460

Cureus. 2026 Jul 23;18(7):e113245. doi: 10.7759/cureus.113245. eCollection 2026 Jul.

ABSTRACT

Background Implant placement in the posterior maxilla is often challenging because of reduced bone density, limited ridge width, and compromised primary stability, particularly in D3 and D4 bone. Conventional osteotomy preparation is subtractive and may further reduce available trabecular bone support. Osseodensification is a bone-preserving osteotomy technique that compacts autogenous bone along the osteotomy walls and may improve peri-implant bone density and ridge dimensions. This study aimed to evaluate the effect of osseodensification on alveolar ridge expansion and peri-implant bone density during implant placement in the D3 and D4 bone of the posterior maxilla. Methodology An institution-based, comparative clinical study was conducted among 20 patients requiring implant-supported fixed prosthetic rehabilitation in the posterior maxilla. Patients were categorized into D3 and D4 bone groups based on preoperative cone-beam computed tomography (CBCT) assessment. Implant osteotomy was performed using Densah burs according to the osseodensification protocol. Peri-implant bone density and alveolar ridge width were measured at the crestal, mid-apical, and apical levels using CBCT at preoperative, immediate postoperative, and four-month postoperative intervals. Intergroup and intragroup comparisons were performed using appropriate statistical tests, with significance set at a p-value <0.05. Results The mean peri-implant bone density in D3 bone increased from 481.5 ± 99.5 HU preoperatively to 578.8 ± 150.0 HU immediately postoperatively and 689.4 ± 193.7 HU at four months. In D4 bone, the mean peri-implant bone density increased from 332.9 ± 78.1 HU preoperatively to 466.7 ± 80.0 HU immediately postoperatively and 588.7 ± 105.6 HU at four months. The intragroup increase in peri-implant bone density was statistically significant in both groups. The mean alveolar ridge width increased from 8.2 mm to 9.8 mm in D3 bone and from 8.0 mm to 8.8 mm in D4 bone. The ridge width gain was more evident at the mid-apical and apical levels than at the crestal level. No significant correlation was observed between age or gender and the evaluated parameters. Conclusions Osseodensification significantly improved peri-implant bone density and produced measurable alveolar ridge expansion in both D3 and D4 bone of the posterior maxilla. The technique appears useful for implant site preparation in low-density posterior maxillary bone. Further controlled clinical studies with larger sample sizes and longer follow-up are required to validate these findings.

PMID:42633460 | PMC:PMC13499619 | DOI:10.7759/cureus.113245

Osteoarthr Cartil Open. 2026 Jul 28;8(3):100852. doi: 10.1016/j.ocarto.2026.100852. eCollection 2026 Sep.

ABSTRACT

OBJECTIVE: A randomized controlled trial (RCT) comparing meniscal repair versus resection is highly needed but may be difficult to perform due to strong surgeon treatment preferences. Therefore, we performed a pilot study to explore orthopaedic surgeons’ willingness-to-randomize meniscal tear patients to inform a future multicentre RCT.

METHOD: Orthopaedic surgeons in The Netherlands (n = 26) and Sweden (n = 1) reviewed 19 arthroscopic video recordings of 19-46-year-old patients with isolated meniscal tears undergoing arthroscopic surgery (meniscal repair/resection). The orthopaedic surgeons reviewed the initial arthroscopic visualization of the knee joint and judged 1) whether they were willing-to-randomize the meniscal tear (yes/no), 2) which meniscal surgery they would perform on the tear (resection, repair, or no surgery), and 3) whether they preferred non-surgical treatment over surgical treatment (yes/no). We used Fleiss kappa with 95% confidence intervals (CI) to estimate agreement.

RESULTS: Twenty-seven knee surgeons with a median [range] of 12 [1-32] years of experience reviewed the videos. The Fleiss Kappa for agreement on whether to randomize a meniscal tear was 0.14 (95% CI 0.03-0.26). Agreement was 0.38 (95% CI 0.25-0.51) for the choice of meniscal surgery and 0.29 (95% CI 0.12-0.45) for preferred treatment option.

CONCLUSION: Orthopaedic surgeons seem to exhibit little agreement as to whether they are willing to randomize a patient with an isolated meniscal tear, but also what treatment option they prefer. Our results suggest 1) an RCT for comparing resection vs repair is needed, and 2) alongside this RCT an observational experiment should evaluate if non-consensus results in pseudo-randomization.

PMID:42633446 | PMC:PMC13499519 | DOI:10.1016/j.ocarto.2026.100852

Int J Chron Obstruct Pulmon Dis. 2026 Aug 18;21:591959. doi: 10.2147/COPD.S591959. eCollection 2026.

ABSTRACT

PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by unpredictable patterns of exacerbations, making continuity of care (CoC) a critical component in disease management. CoC influences COPD exacerbation-related hospitalization and mortality. Therefore, we assessed the impact of CoC levels on subsequent hospital admissions and all-cause mortality among individuals with COPD.

PATIENTS AND METHODS: This retrospective nationwide cohort study utilized National Health Insurance Service-Senior cohort data (2002-2019) and included 29,316 patients newly diagnosed with COPD. The primary exposure was longitudinal CoC level categorized as low (<0.7) or high (≥0.7). Alternative continuity indices (usual care provider, sequential continuity, and modified continuity indices) were also evaluated. Outcomes were COPD exacerbation-related hospitalization and all-cause mortality within 1 year of diagnosis. Cox proportional hazards models estimated hazard ratios (HRs), Kaplan-Meier curves, and cumulative incidence rates were used to assess outcomes, and the Log rank test was used for between-group comparisons.

RESULTS: Low CoC level were associated with an increased risk of 3-year COPD exacerbation-related hospitalization (HR 1.63, 95% CI 1.45-1.83) and all-cause mortality (HR 1.25, 95% CI 1.11-1.40) compared with high CoC level. Intermediate (0.4-0.7) and low (<0.4) CoC level showed progressively increased hospitalizations (HR 1.61, 95% CI 1.40-1.86 vs HR 1.65, 95% CI 1.38-1.97), and mortality (HR 1.24, 95% CI 1.07-1.43 vs HR 1.26, 95% CI 1.05-1.51), respectively. These findings remained consistent across alternative continuity indices. Low CoC level were associated with an increased risk of emergency (HR 1.48, 95% CI 1.19-1.83) and general hospital admissions (HR 1.70, 95% CI 1.47-1.95).

CONCLUSION: Lower CoC scores level consistently associated with higher risks of COPD hospitalization and all-cause mortality across multiple continuity indices. Subgroup and sensitivity analyses indicated that fragmented outpatient care increased adverse outcomes. Strengthening longitudinal patient-provider relationships may reduce preventable hospitalizations and premature deaths in patients with COPD.

PMID:42633418 | PMC:PMC13499550 | DOI:10.2147/COPD.S591959

EClinicalMedicine. 2026 Aug 15;99:104157. doi: 10.1016/j.eclinm.2026.104157. eCollection 2026 Sep.

NO ABSTRACT

PMID:42633408 | PMC:PMC13499450 | DOI:10.1016/j.eclinm.2026.104157

JPRAS Open. 2026 Jul 26;51:685-696. doi: 10.1016/j.jpra.2026.07.032. eCollection 2026 Sep.

ABSTRACT

OBJECTIVES: This study aimed to quantitatively compare alterations in upper airway dimensions-specifically volume and cross-sectional area-following isolated mandibular setback versus bimaxillary surgery using the surgery-first approach (SFA) in patients with skeletal Class III malocclusion. To the best of our knowledge, this is the first study to directly compare these two surgical protocols exclusively under the SFA paradigm with acoustic pharyngometry and per-millimetre analysis over a 1-year follow-up.

MATERIALS AND METHODS: A retrospective cohort investigation was conducted on 40 skeletally mature Class III adults, equally allocated into two cohorts: Group 1 underwent isolated mandibular setback via bilateral sagittal split osteotomy (BSSO, n=20), while Group 2 received bimaxillary orthognathic surgery (maxillary advancement combined with mandibular setback, n=20). Upper airway parameters were objectively assessed using acoustic pharyngometry at three distinct intervals: one week preoperatively (T0), one month postoperatively (T1), and one year postoperatively (T2). Spatial airway variations were quantified as percentage changes, with the magnitude of airway reduction and subsequent recovery calculated per millimetre (mm) of surgical mandibular setback.

RESULTS: At T1, both surgical interventions resulted in a statistically significant reduction in airway dimensions. Nevertheless, the extent of airway constriction was markedly more severe in Group 1 compared to Group 2, affecting both volume (-22.84% vs. -7.96%; p < 0.01) and cross-sectional area (-21.45% vs. -6.79%; p < 0.01). The volumetric reduction per millimetre of mandibular setback in Group 1 was -1.168 cc/mm, which was substantially greater than the -0.458 cc/mm observed in Group 2 (p < 0.01). By T2, a distinct airway recovery (relapse) was documented; Group 1 exhibited a higher volumetric recovery rate (+15.83%) than Group 2 (+4.63%). Despite this rebound, the overall airway dimensions at the one-year follow-up (T2) remained significantly larger and better preserved in the bimaxillary cohort than in the isolated setback group (p < 0.05).

CONCLUSIONS: Performing an isolated mandibular setback under the SFA protocol induces considerable upper airway constriction. Conversely, incorporating maxillary advancement via bimaxillary orthognathic surgery significantly preserves airway dimensions. Consequently, bimaxillary intervention should be considered a safer surgical indication to proactively mitigate the risk of respiratory impairment, particularly in Class III patients requiring substantial mandibular retropositioning. This study provides new evidence that bimaxillary surgery better preserves airway dimensions in SFA compared with isolated mandibular setback.

PMID:42633400 | PMC:PMC13499473 | DOI:10.1016/j.jpra.2026.07.032