Category: Nevin Manimala

Ren Fail. 2026 Dec;48(1):2694246. doi: 10.1080/0886022X.2026.2694246. Epub 2026 Jul 2.

ABSTRACT

BACKGROUND: Patients with advanced chronic kidney disease (CKD) and dyslipidemia are at high risk of kidney failure and cardiovascular events, yet many do not receive lipid-lowering therapy. Pentoxifylline (PTX) has anti-inflammatory and antifibrotic properties, but its association with hard cardiorenal outcomes remains uncertain.

METHODS: We conducted a retrospective cohort study of adults with stage 3b-5 CKD and dyslipidemia enrolled in a pre-end-stage renal disease program from 2007 to 2018. Patients receiving lipid-lowering therapy were excluded. PTX initiators were matched 1:1 to nonusers using propensity score matching. The primary outcome was progression to end-stage kidney disease (ESKD). Secondary outcomes included major adverse cardiovascular events (MACE), 50% estimated glomerular filtration rate decline within 2 years, and doubling of serum creatinine. Sensitivity analyses included time-varying exposure, lag, and landmark analyses.

RESULTS: Among 3,542 eligible patients, 2,776 were included in the matched cohort. PTX use was associated with lower risks of ESKD (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.75-0.96) and MACE (HR, 0.80; 95% CI, 0.65-0.98). No significant associations were observed for short-term kidney function decline or creatinine doubling. Time-related sensitivity analyses attenuated estimates toward the null but did not suggest harm.

CONCLUSION: In patients with advanced CKD and untreated dyslipidemia, PTX use was associated with lower risks of kidney failure in propensity score-matched analyses, whereas the association with cardiovascular events was less robust after sensitivity analyses. These findings require cautious interpretation and further validation.

PMID:42393494 | DOI:10.1080/0886022X.2026.2694246

Ren Fail. 2026 Dec;48(1):2678061. doi: 10.1080/0886022X.2026.2678061. Epub 2026 Jul 2.

ABSTRACT

BACKGROUND: Urological complications remain a significant source of morbidity following kidney transplantation, often leading to re-intervention and graft dysfunction. Although advances in surgical technique and perioperative care have reduced incidence rates, controversy persists regarding risk predictors and the prophylactic role of double-J ureteral stenting.

METHODS: We retrospectively analyzed 425 adult kidney transplant recipients at a single tertiary center between January 2008 and December 2023. Patient demographics, donor characteristics, surgical variables, and postoperative outcomes were reviewed. Complications were defined as urinary leak, ureteral stricture, or anastomotic obstruction requiring intervention within 12 months. Data were compared across three eras (2008-2012, 2013-2017, 2018-2023). Multivariable logistic regression identified independent risk factors.

RESULTS: Overall, 11.1% (n = 47) of patients developed urological complications. Ureteral stricture was the most frequent (57%), followed by urinary leak (28%) and anastomotic obstruction (15%). Older recipient age (OR 1.04, 95% CI 1.01-1.07, p = 0.012), re-transplantation (OR 2.95, 95% CI 1.12-7.77, p = 0.028), and deceased donor grafts (OR 2.17, 95% CI 1.12-4.19, p = 0.021) were independent predictors. Prophylactic double-J ureteral stenting demonstrated a non-significant protective trend (OR 0.71, 95% CI 0.44-1.15, p = 0.091). Routine stenting in Era 3 coincided with a non-significant reduction in leak and stricture rates.

CONCLUSION: Older age, re-transplantation, and deceased donor grafts independently predicted complications, while prophylactic stenting showed a non-significant protective effect. Further multicenter studies are needed to validate these findings and optimize stent protocols.

PMID:42393492 | DOI:10.1080/0886022X.2026.2678061

Shock. 2026 Jul 2. doi: 10.1097/SHK.0000000000002891. Online ahead of print.

ABSTRACT

INTRODUCTION: Smoke inhalation injury alone or combined with burns and other traumas remains a serious threat for military members as well as the civilian population. It causes acute respiratory distress syndrome requiring life-saving interventions (LSI), including various respiratory support e.g., oxygen supplementation, intubation, and non-invasive or invasive mechanical ventilation. While potentially scarce in austere environments and/or during mass casualties, LSI require trained personnel, equipment, and resources. In this study, we tested the hypothesis that nebulized epinephrine can delay the need for LSI using the clinically relevant ovine model of smoke inhalation.

METHODS: Adult Merino female sheep were surgically instrumented with multiple catheters five to seven days prior to the study. After recovery from surgery, sheep were subjected to smoke inhalation (48 breaths of cooled cotton smoke inhalation below 40°C) under anesthesia and analgesia. Then, sheep were randomly allocated to two groups. Sheep in the control group were injured and treated with saline nebulization (n=6). Sheep in the treatment group were injured and treated with epinephrine nebulization (n=6). Nebulization was started immediately following injury and repeated every 4 hours.After the smoke inhalation injury, sheep were allowed to spontaneously breath room-air via a mechanical ventilator set with PEEP=0 and pressure support (PS)=0, which is equal to no mechanical support. An arterial blood gas analysis was determined every hour to adjust respiratory support, if needed. The changes in FiO2, PaO2/FiO2 ratio, PEEP, and P support were recorded every hour from the onset of smoke injury.The primary outcomes were variables comparing of oxygen demand, PaO2/FiO2 ratio, PEEP, and P support as representatives of the LSI. The secondary outcomes were comparison of systemic hemodynamics, bloodless lung wet-to-dry weight ratio, and histological analysis. Statistical significance was set at P<0.05.

RESULTS: The time from the onset of smoke injury until the FiO2 increased over 25% in the treatment group was significantly longer than in the control group (p=0.0406). The time until the FiO2 increased over 30% in the treatment group was significantly longer (p=0.0474). The time until the PaO2/FiO2 ratio decreased below 300 in the treatment group was significantly longer than in the control group (p=0.0195). The time for the increase in PEEP over 5 cmH2O in the treatment group was significantly delayed compared to the control group (p=0.0050). One animal in the control group required positive pressure mechanical ventilation vs. zero in the treatment group.

CONCLUSIONS: The present data indicate that nebulized epinephrine delays the need for LSI following smoke inhalation injury in ovine model. If it is also effective in humans, nebulized epinephrine may be immediately used at the injury site as an effective resuscitation tool for smoke inhalation victims until they are admitted to the hospital for more progressive care.

PMID:42393491 | DOI:10.1097/SHK.0000000000002891

Dig Dis Sci. 2026 Jul 2. doi: 10.1007/s10620-026-10086-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Rapid gastric emptying (RGE) is conventionally defined as ≥ 70% emptying of a standardized solid meal at 1 h using gastric emptying scintigraphy (GES). However, this threshold is not universally adopted, and variability exists in how accelerated gastric emptying is defined in practice. We aimed to better characterize patients with conventionally defined RGE as well as those with accelerated emptying not meeting this threshold, and to evaluate what clinical differences exist across varying degrees of accelerated gastric emptying.

METHODS: We identified a cohort of 258 adult patients (≥ 18 years old) with increased gastric emptying (≥ 30% emptied at 1 h) at a tertiary medical center. Patients with a history of esophageal, gastric or thoracic surgery were excluded. Patients were stratified into three cohorts based on 1-h gastric emptying percentages: 30-49%, 50-69%, and ≥ 70%. Manual chart review was performed to extract data on demographics, medications, laboratory values, GES indications, and management changes resulting from GES findings.

RESULTS: The majority of patients (n = 205, 79.4%) were in the 30-49% emptying cohort. Only 10 patients (3.9%) met the conventional threshold of ≥ 70% emptying at 1 h. The most common indications for GES were nausea (39.1%), vomiting (33.7%), and abdominal pain (25.6%), with no statistically significant differences in indications across the 3 cohorts. Furthermore, there were no differences in age, sex, BMI, comorbidities, medications, or management changes between the cohorts.

CONCLUSIONS: RGE that meets current consensus criteria is uncommon in clinical practice. Clinical characteristics and interventions were similar among cohorts with different degrees of accelerated emptying. The current cutoff of ≥ 70% emptying at 1 h may not represent a clinically distinct phenotype, emphasizing the need for better criteria to guide diagnosis and management.

PMID:42393488 | DOI:10.1007/s10620-026-10086-6

BioDrugs. 2026 Jul 2. doi: 10.1007/s40259-026-00795-9. Online ahead of print.

ABSTRACT

BACKGROUND: Ustekinumab biosimilars have expanded treatment options for moderate-to-severe plaque psoriasis, but pooled evidence is needed to determine whether they achieve therapeutic equivalence to reference ustekinumab during the initial randomized comparative period before protocol-defined switching.

OBJECTIVES: The aim of this systematic review was to assess the therapeutic equivalence of ustekinumab biosimilars versus reference ustekinumab during the pre-switch period in adults with moderate-to-severe plaque psoriasis.

METHODS: We searched PubMed, Embase, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and trial registries from inception to 15 October 2025 for phase III randomized clinical trials comparing ustekinumab biosimilars or follow-on biologics with reference ustekinumab and reporting comparative data before switching. Data were extracted independently by two reviewers. Risk of bias was assessed using the Risk of Bias 2 (RoB 2) tool, and certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Random-effects meta-analysis with Hartung-Knapp-Sidik-Jonkman 95% confidence intervals (CIs) was performed. The primary outcome was 75% improvement in Psoriasis Area and Severity Index (PASI 75) response at week 12, analyzed using risk differences with a prespecified equivalence margin of ± 10%.

RESULTS: Nine randomized trials including 4532 participants were analyzed. At week 12, the pooled risk difference for PASI 75 was 0.02 (95% CI -0.02 to 0.05), meeting the prespecified ± 10% equivalence criterion, with low between-study heterogeneity (I² statistic = 6%). Equivalence-consistent estimates were also observed for PASI 90 (risk difference – 0.01, 95% CI – 0.06 to 0.03) and PASI 100 (risk difference 0.00, 95% CI – 0.03 to 0.03). Treatment-emergent adverse events were comparable through week 28 (risk difference 0.01, 95% CI – 0.04 to 0.06). At week 12, anti-drug antibody detection was lower in biosimilar arms (risk difference – 0.14, 95% CI – 0.23 to – 0.04), which may partly reflect assay variability rather than clinically meaningful differences. No material differences were observed in short-term pre-switch clinical response, patient-reported quality of life, or safety.

CONCLUSIONS: During the initial randomized comparative period, ustekinumab biosimilars met prespecified therapeutic equivalence criteria for PASI 75 and showed equivalence-consistent results for PASI 90 and PASI 100, with comparable short-term safety versus reference ustekinumab. These findings provide pooled reassurance across standard and stringent skin-clearance outcomes during a clinically relevant early treatment window.

REGISTRATION: PROSPERO (CRD420251166323). Registered October 12, 2025.

PMID:42393486 | DOI:10.1007/s40259-026-00795-9

Med Biol Eng Comput. 2026 Jul 3. doi: 10.1007/s11517-026-03618-9. Online ahead of print.

ABSTRACT

The hemoglobin concentration in blood is vital for diagnosing anemia and monitoring the various health conditions. However, conventional measurement methods need invasive blood sampling so that they might have limited accessibility and uncomfortable for patients. Today, non-invasive alternatives powered by machine learning techniques provide promising solutions for point-of-care facilities and remote healthcare systems. This paper presents a methodology through a comprehensive research and development process to estimate hemoglobin levels from facial videos using multi-modal feature extraction and ensemble learning techniques. A dataset of 260 participants with various blood hemoglobin levels was processed to extract the features from pre-trained convolutional neural-networks (MobileNetV2, ResNet152), remote photoplethysmography (rPPG) signals, and color statistical features. Using these features, hemoglobin concentration was estimated via a number of machine learning models including XGBoost, Random Forest, and Stacking Regressor, respectively. Stacking Regressor provided the best estimation scores with a mean-absolute error of 0.7754 g/dL, Pearson correlation-coefficient of 0.7878, and [Formula: see text] score of 0.5852. ResNet152 model based features were combined with XGBoost, which achieved comparable performance (MAE: 0.6635 g/dL, [Formula: see text]: 0.4977). Experimental results demonstrated that multi-modal feature strategy outperformed single-modality approaches in terms of prediction accuracy and robustness. The proposed video-based estimation of hemoglobin concentration system achieves clinically relevant accuracy levels, outperforms to literature methods, comparable to point-of-care instruments demonstrating strong potential for use in anemia screening and remote patient monitoring.

PMID:42393483 | DOI:10.1007/s11517-026-03618-9

Drug Saf. 2026 Jul 2. doi: 10.1007/s40264-026-01693-3. Online ahead of print.

ABSTRACT

BACKGROUND: Medication shortages are a considerable and ongoing issue in healthcare, disrupting consumer access to medicines. Since 2021, Australia’s national medicines regulator has issued Serious Scarcity Substitution Instruments (SSSIs), allowing pharmacists to substitute a specific therapeutically equivalent strength and/or formulation of a medicine without prior approval from a prescriber. The impact of SSSIs on utilisation of medicines has not been investigated.

OBJECTIVE: To determine whether SSSIs are effective in addressing medicine shortages and meeting patients’ needs.

METHODS: This retrospective cohort study used aggregated pharmacy claims to examine the utilisation of 12 medicines, which had an SSSI. We calculated the percentage change in defined daily doses dispensed per 1000 population per day in the 11 months after SSSI implementation, compared with the previous 2 years. A percentage change of less than 20% was used to indicate success.

RESULTS: Following medicine shortages, utilisation fell for 10 of the 12 medicines examined. For eight of these medicines (amoxicillin, cefalexin, estradiol, fluoxetine, insulin degludec with insulin aspart, isosorbide mononitrate, vigabatrin, and warfarin) decreases in utilisation were minimised to < 20%. On average, SSSIs where all permitted substitute products were scarce (e.g., abatacept) were associated with larger decreases in use (between – 22 and – 68%) than those for which none or only some of the substitutes were in shortage (between – 45 and + 7%, respectively).

CONCLUSIONS: While product shortages led to decreases in medicines consumption, SSSIs appeared to be successful in limiting decreases. However, SSSIs were less likely to be successful when many of the permitted substitute products were also scarce.

PMID:42393456 | DOI:10.1007/s40264-026-01693-3

J Magn Reson Imaging. 2026 Jul 2. doi: 10.1002/jmri.70431. Online ahead of print.

ABSTRACT

BACKGROUND: Susceptibility alterations in deep gray matter (DGM) nuclei after acute ischemic stroke (AIS) may relate to impaired functional independence. However, conventional quantitative susceptibility mapping (QSM) cannot separate paramagnetic iron-related from diamagnetic myelin-related sources, potentially obscuring relevant pathophysiological alterations.

PURPOSE: To apply χ-separation to disentangle paramagnetic susceptibility (χ_para) and diamagnetic susceptibility (χ_dia) in DGM nuclei after AIS and assess associations with 3-month functional independence.

STUDY TYPE: Prospective.

POPULATION: 82 AIS patients (52 M/30 F) and 82 healthy controls (49 M/33 F).

FIELD STRENGTH/SEQUENCE: 3 T; 3D multi-echo gradient-echo sequence for QSM and χ-separation reconstruction.

ASSESSMENT: χ_para and χ_dia were measured in the caudate, putamen, globus pallidus, substantia nigra, red nucleus, thalamus, and dentate nucleus. Contralesional nuclei were analyzed in patients. Group differences and 3-month outcome associations were assessed. Functional independence was defined as modified Rankin Scale score 0-2, and poor outcome as 3-6.

STATISTICAL TESTS: Linear mixed-effects models, analysis of covariance, logistic regression, receiver operating characteristic analysis; p < 0.05 was significant.

RESULTS: Compared with healthy controls, patients showed higher χ_para in all seven nuclei, including the dentate nucleus (84.065 ± 15.086 vs. 76.172 ± 11.387 ppb) and thalamus (30.633 [28.036, 34.454] vs. 28.867 [26.749, 31.804] ppb), and higher χ_dia in the caudate, putamen, red nucleus, thalamus, and dentate nucleus (dentate nucleus: -18.916 ± 6.496 vs. -22.220 ± 5.002 ppb). Poor 3-month outcome was independently associated with higher dentate nucleus χ_para (OR, 1.07; 95% CI, 1.03-1.11), higher dentate nucleus χ_dia (OR, 1.14; 95% CI, 1.04-1.26), and higher thalamus χ_para (OR, 1.22; 95% CI, 1.08-1.38). The combined model, incorporating conventional model factors (age, sex, stroke subtype, NIHSS score, and infarct volume) and χ-separation metrics, outperformed the conventional model (AUC, 0.862 vs. 0.757).

DATA CONCLUSION: χ-separation revealed iron- and myelin-related susceptibility alterations in contralesional DGM nuclei after AIS. Susceptibility metrics in the dentate nucleus and thalamus were associated with poor 3-month functional outcome.

EVIDENCE LEVEL: 2.

TECHNICAL EFFICACY: Stage 1.

PMID:42393438 | DOI:10.1002/jmri.70431

Diabetologia. 2026 Jul 2. doi: 10.1007/s00125-026-06790-7. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: The aim of this study was to examine whether the independent and joint effects of obesity and alcohol consumption on diabetes risk differ when exposures are assessed at baseline or as time-varying variables, and whether interaction patterns vary across multiplicative and additive scales in a Asian prospective cohort.

METHODS: In total, 7817 participants aged ≥40 years without diabetes at baseline (2001-2002) were followed until 2017-2018, and the associations of obesity and alcohol consumption with incident diabetes and their interactions were assessed using Cox proportional hazards and Aalen’s additive hazards models.

RESULTS: Obesity and high alcohol consumption (≥30 g/day) were consistently associated with incident diabetes across all analyses, with stronger associations observed in the time-varying models. Obesity (HR 1.91; 95% CI 1.75, 2.09; 21.9 additional cases per 1000 person-years; 95% CI 20.0, 23.8) and high alcohol consumption (HR 1.23; 95% CI 1.05, 1.44; 14.6 additional cases per 1000 person-years; 95% CI 11.1, 18.1) were both associated with increased diabetes risk. Associations for low-to-moderate alcohol consumption were weaker, and were statistically significant only on the additive scale. No significant multiplicative interactions were observed for the effect of baseline or time-varying obesity, current alcohol consumption or daily alcohol consumption on the risk of diabetes. However, significant antagonistic additive interactions were observed between baseline or time-varying obesity and current alcohol consumption: drinking <10 g/day with 12.8 fewer cases/1000 person-years (95% CI -17.4, -8.2), 10-29.9 g/day with 15.9 fewer cases (95% CI -22.1, -9.8), and ≥30 g/day with 14.6 fewer cases (95% CI -22.0, -7.2), with a p_interaction value <0.001. Joint analysis revealed that, in participants with obesity, the increased association with low-to-moderate alcohol consumption was minimal in terms of multiplicative and additive models, especially for time-varying exposures. The results were comparable in the sensitivity analysis that was restricted to baseline current drinkers, in which current drinkers consuming <10 g/day of alcohol were used as the reference group.

CONCLUSIONS/INTERPRETATION: Obesity and high alcohol consumption were consistently associated with incident diabetes, and an antagonistic additive interaction was observed between obesity and all alcohol consumption levels. These findings highlight the importance of exposure modelling and scale choice, and support prioritising weight management and reducing high alcohol consumption in diabetes prevention.

PMID:42393406 | DOI:10.1007/s00125-026-06790-7

Diabetologia. 2026 Jul 2. doi: 10.1007/s00125-026-06788-1. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: In healthy lean humans, endogenous glucose-dependent insulinotropic polypeptide (GIP) contributes significantly to the postprandial increase in arteria mesenterica superior blood flow. The vascular biology related to activation of the GIP receptor is markedly impaired in individuals with type 2 diabetes and is sometimes absent. In this population, we investigated the role of endogenous GIP on postprandial splanchnic blood flow by using the GIP receptor antagonist, GIP(3-30)NH₂. The primary outcome of this study was the changes in blood flow in arteria mesenterica superior during oral glucose with or without GIP receptor antagonist infusion.

METHODS: Ten participants with type 2 diabetes (age 20-80 years, BMI 20-35 kg/m², and HbA_1c >48 mmol/mol and <75 mmol/mol) were investigated in a randomised, placebo-controlled, crossover study. On four separate occasions, participants received the following treatment: oral glucose + i.v. GIP(3-30)NH₂; oral glucose + i.v. saline (154 mmol/l NaCl); oral water + i.v. GIP(3-30)NH₂; oral water + i.v. saline. Participants were randomly assigned to intervention groups using (random.org). Participants were unaware of allocation, while investigators were aware. No additional allocation concealment procedures were used. During all four interventions, splanchnic blood flow was measured using phase-contrast MRI in the arteria mesenterica superior, truncus coeliacus and vena portae during oral glucose (75 g) or water ingestion. The study was conducted at Rigshospitalet, Copenhagen. Liver volume and oxygenation, as well as gallbladder volume, were assessed. Blood samples were collected and analysed for insulin, C-peptide, GIP, glucagon and glucose.

RESULTS: Oral glucose alone increased mean blood flow in arteria mesenterica superior by 57% (95% CI 26, 88) and this was 15% (95% CI -2, 32) lower during concomitant GIP receptor antagonist infusion, p=0.012. Infusion of GIP receptor antagonist during oral glucose treatment did also result in lower insulin secretion, C-peptide and C-peptide/glucose ratio compared with saline infusion, whereas glucagon levels and plasma glucose were unaffected. Oral water did not affect any outcomes.

CONCLUSIONS/INTERPRETATION: Endogenous GIP contributes to postprandially increased splanchnic blood flow in people with type 2 diabetes.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06426823 FUNDING: This work was supported by the Novo Nordisk Foundation.

PMID:42393405 | DOI:10.1007/s00125-026-06788-1