Nevin Manimala

Ann Pharmacother. 2026 Jan 28:10600280251393677. doi: 10.1177/10600280251393677. Online ahead of print.

ABSTRACT

BACKGROUND: Intravenous fluids are commonly used in postcardiac surgery to maintain or increase intravascular volume. While volume expansion after cardiac surgery is often necessary, the optimal fluid type to use is not established.

OBJECTIVE: The objective of the study is to evaluate cost-savings and clinical outcomes of an albumin minimization protocol for postcardiac surgery fluid resuscitation at a surgical intensive care unit in a community teaching hospital.

METHODS: This was a single-center retrospective cohort study of patients who received fluid resuscitation after open heart coronary artery bypass surgery or valvular surgery while on cardiopulmonary bypass at a community teaching hospital between February 2021 and May 2022. Cohorts were split up prior to the implementation of an albumin minimization protocol that was implemented in September 2021. The primary outcome was the amount of albumin or crystalloid fluids received after surgery, and the overall cost of intravenous fluids after surgery. Secondary outcomes included 30-day mortality, acute kidney injury, hours on oxygen support, hours on vasopressors, multiple vasopressors used, perioperative blood product transfusions, and 72-hour surgery take back.

RESULTS: Of 434 total patients evaluated, 400 patients met criteria for inclusion. Baseline characteristics were balanced between the 2 groups. Average surgical time was shorter in the postprotocol arm. Per patient use of albumin decreased by 27.1 g (22.8-31.4) while crystalloid fluid use increased by 1 L (0.9-1.2) after implementation of the albumin minimization protocol. Average cost savings were approximately $178 per surgery. No statistically significant difference was seen in any of the secondary safety and efficacy outcomes.

CONCLUSION AND RELEVANCE: This study adds to the body of literature suggesting that the use of an albumin minimization protocol after open heart cardiac surgery was safe and effective. A significant reduction in cost and utilization of albumin was seen in the study without affecting patient outcomes.

PMID:41604250 | DOI:10.1177/10600280251393677

Plast Reconstr Surg. 2026 Jan 22. doi: 10.1097/PRS.0000000000012839. Online ahead of print.

ABSTRACT

BACKGROUND: Discrepancies between assigned and actual operative durations may distort time-based valuation of surgical procedures. This study evaluated the impact of operative time source on wRVU per minute and reimbursement per minute across commonly reimbursed reconstructive plastic surgery operations.

METHODS: Using 2023 National Surgical Quality Improvement Program (NSQIP) data, we compared actual operative times for 11 commonly reimbursed plastic surgery procedures to CMS-assigned times from the Physician Fee Schedule. Each CPT (15830, 19316, 19318, 19325, 19340, 19342, 19357, 19364, 19370, 19371, 19380) was linked to its CMS-assigned wRVU. wRVU per minute and reimbursement per minute were calculated using both NSQIP-observed and CMS-assigned operative times. Statistical analyses included Wilcoxon signed-rank tests, Kruskal-Wallis tests, Spearman correlations, and multivariable linear regression.

RESULTS: Among 6,537 single-CPT cases, CMS underestimated operative time in 5 of 11 procedures. The largest discrepancies were observed in immediate implant insertion (+93.5 min), free flap breast reconstruction (+60.5 min), and breast augmentation (+18.5 min), resulting in reduced wRVU/min and $/min. Time discrepancy correlated strongly with reduced wRVU/min (ρ=-0.84). NSQIP-modeled reimbursement showed 2,637 single-CPT cases (40.3%) as underpaid, totaling $751,149.18. Among 15,570 multi-CPT cases, 5,099 (32.7%) were under-reimbursed, with a cumulative modeled underpayment of $2,002,956.29.

CONCLUSIONS: CMS operative times frequently underestimated the duration of plastic surgery procedures. Time discrepancies were associated with substantial reductions in wRVU/min and $/min, particularly for complex or implant-based operations. These findings suggest that current CMS time assignments do not adequately capture operative complexity and may contribute to systematic underpayment in reconstructive surgery.

PMID:41604240 | DOI:10.1097/PRS.0000000000012839

Acta Ophthalmol. 2026 Jan 28. doi: 10.1111/aos.70063. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate changes in corneal tomography, pachymetry and endothelial cell density (ECD) following Paul Glaucoma Implant (PGI) surgery.

METHODS: Seventy-three patients were prospectively examined. Repeated measures anova was used to analyse corneal tomography, corneal thickness and ECD at baseline, 6 and 12 months.

RESULTS: PGI surgery was not associated with clinically meaningful changes in corneal tomography parameters. Simulated astigmatism and posterior astigmatism remained stable over 12 months. Simulated average keratometry showed a small but statistically significant flattening (≈0.3 diopters), whereas posterior average keratometry remained unchanged. Although some changes reached statistical significance, their magnitude was minimal and unlikely to be clinically relevant. Central corneal thickness remained stable, but pachymetry in the tube quadrant increased in the operated eyes, while adjusted pairwise comparisons were non-significant. Central ECD did not change significantly after surgery (p = 0.67). In contrast, paracentral (-2.9%) and peripheral (-4.7%) ECD values declined significantly over 12 months (p = 0.03 and p = 0.001, respectively) and study eyes consistently showed lower values than contralateral control eyes. However, PGI surgery did not accelerate the rate of cell loss, as the time × eye interaction was not significant.

CONCLUSIONS: PGI surgery did not induce progressive changes in corneal astigmatism or pachymetry during the first postoperative year. Central ECD remained stable, while paracentral and peripheral regions showed a moderate decline. PGI did not increase the rate of endothelial cell loss and the observed reduction was lower than previously reported for other glaucoma drainage implants.

PMID:41604236 | DOI:10.1111/aos.70063

J Magn Reson Imaging. 2026 Jan 28. doi: 10.1002/jmri.70204. Online ahead of print.

ABSTRACT

BACKGROUND: Skeletal muscle blood oxygen level dependent (BOLD) MRI is a technique for assessing vascular function in peripheral limbs. In patients, however, an increased frequency of atypical response patterns has been observed, warranting investigation into its underlying causes.

PURPOSE: To explore the dynamics of cuff-induced ischemia and reactive hyperemia with BOLD MRI, focusing on the occurrence, quantification, and interpretation of frequent atypical cuff-induced response patterns.

STUDY TYPE: Secondary assessment of prospectively collected datasets.

POPULATION: Seventeen peripheral artery disease (PAD) patients (age: 64-80 years, ankle-brachial index (ABI) range: 0.4-0.8), 8 age-matched controls (age: 64-82 years, ABI range: 1-1.2), and 14 young controls (age: 22-39 years). FIELD STRENGTH/SEQUENCE: $T_2^{*}$ -weighted multi-echo gradient-echo sequence with 11 equidistant echo-times at 3T.

ASSESSMENT: A transverse slice of the calf was imaged repeatedly during an upper-thigh cuff compression cycle consisting of 1-min baseline, 5-min arterial occlusion (cuff inflated) and 5-min reactive hyperemia (cuff deflated). $T_2^{*}$ -mapping with ROI-wise analysis of the soleus and gastrocnemius muscles produced $T_2^{*}$ -time curves and previously established metrics, including the hyperemic upslope ( ${\mathrm{HS}}_{\mathrm{up}}$ ) and time-to-peak (TTP) were assessed. The time-curves were surveyed to identify the frequency and type of deviations from expected. $T_2^{*}$ -time curves of soleus were further analyzed by fitting a parameterized function to derive additional metrics including depth of the undershoot on cuff release and deviation from a monotonic T2* decrease. Ankle-brachial index (ABI) served as a clinical reference for comparisons.

STATISTICAL TESTS: Non-parametric 2-tailed Wilcoxon rank-sum tests to assess differences between patients and age-matched controls. A p value < 0.05 was considered significant.

RESULTS: Atypical cuff-induced response patterns in PAD patients included a negative cuff-induced transient (42%, soleus) and non-monotonic declines in $T_2^{*}$ during cuffing (58%, soleus). While these contributed to increased variabilities in patients, $\text{there were significant differences in}{\mathrm{HS}}_{\mathrm{up}}$ (-0.63 ms/s) and TTP (62.8 s) between patients and age-matched controls.

DATA CONCLUSION: HS_up and TTP provided means to quantify calf muscle responses to cuffing. Specific cases of non-monotonous $T_2^{*}$ decrease during cuffing suggest the detection of venous valve leakages in inter-muscular veins. Insufficient cuff pressure produced curves with absent ischemic plateau and weak hyperemic responses, the recognition of which is important to prevent physiological misinterpretations of $T_2^{*}–\text{time}$ curves and derived metrics.

EVIDENCE LEVEL: 1.

TECHNICAL EFFICACY: 3.

PMID:41604213 | DOI:10.1002/jmri.70204

JAMA. 2026 Jan 28. doi: 10.1001/jama.2025.25686. Online ahead of print.

NO ABSTRACT

PMID:41604184 | DOI:10.1001/jama.2025.25686

JAMA Dermatol. 2026 Jan 28. doi: 10.1001/jamadermatol.2025.5662. Online ahead of print.

ABSTRACT

IMPORTANCE: Currently, there are no treatments approved by the US Food and Drug Administration for juvenile localized scleroderma (JLS), a rare disease. While methotrexate (MTX) is regularly used as a first-line therapy, emerging data from case series and applications in systemic sclerosis suggest that mycophenolate mofetil (MMF) may be clinically comparable, with potential benefits in tolerability and adherence.

OBJECTIVE: To compare clinical outcomes of patients with JLS treated with MTX and MMF using standardized clinical outcome measures.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of patients with clinician-diagnosed JLS who were enrolled in the National Registry of Childhood Onset Scleroderma was conducted at UPMC Children’s Hospital of Pittsburgh. Data were from January 2010 to January 2023 and first analyzed in April 2023. All patients were evaluated and followed up by the same physician. Patients were included if they had disease onset before age 18 years and a localized scleroderma diagnosis and enrollment in the National Registry of Childhood Onset Scleroderma before age 21 years. Patients were required to be receiving MTX monotherapy, MMF monotherapy, or combination therapy (CT) of the 2 for their localized scleroderma.

EXPOSURES: Patients were treated with MTX, MMF, or CT as prescribed by the examining physician.

MAIN OUTCOMES AND MEASURES: This study measured comparative medication treatment response through associations with disease activity, as measured using the Localized Scleroderma Cutaneous Assessment Tool.

RESULTS: Of 114 patients, 77 (67.5%) were female, and the median (IQR) age at onset was 8.3 (5.4-11.2) years. The MTX, MMF, and CT groups included 68 (59.6%), 28 (24.6%), and 18 patients (15.8%), respectively. There were no significant differences in baseline demographic characteristics, disease subtype, or disease severity between groups, but patients in the MMF group had longer disease duration. Mixed-effects modeling showed statistically significant decreases in activity across all groups (β = -0.14; 95% CI, -0.62 to 0.33). A Kaplan-Meier analysis showed no significant difference in disease flare rate over the follow-up interval (hazard ratio, 0.85; 95% CI, 0.51-1.33). However, patients treated with MTX compared with those treated with MMF had significantly higher rates of fatigue (47% vs. 11%, P = .001) and nausea (60% vs. 7%; P = .001).

CONCLUSIONS AND RELEVANCE: The study results suggest that MMF demonstrated a similar response to treatment as MTX in reducing disease activity in JLS, with comparable flare rates and improved tolerability. These initial findings support MMF as a potential candidate for first-line treatment of JLS. Prospective, randomized, noninferiority trials are warranted to confirm these results and guide future treatment recommendations.

PMID:41604178 | DOI:10.1001/jamadermatol.2025.5662

JAMA Dermatol. 2026 Jan 28. doi: 10.1001/jamadermatol.2025.5700. Online ahead of print.

ABSTRACT

IMPORTANCE: Cutaneous squamous cell carcinoma (cSCC), cSCC in situ (CIS), and keratoacanthoma (KA) pose growing public health challenges, due to their associated morbidity, health care burden and costs. However, many countries lack systematic registration of these extremely frequent keratinocyte neoplasms.

OBJECTIVE: To estimate incidence rates and trends of first-time, histologically confirmed cSCC, CIS, and KA in Denmark (2005-2023) by sex, age, and anatomical site.

DESIGN, SETTING, AND PARTICIPANTS: A nationwide, population-based study using data from the Danish Pathology Registry and Cancer Registry was conducted, including individuals 20 years or older receiving a first-time diagnosis of cSCC, CIS, or KA from January 1, 2005 to December 31, 2023. Data analyses were conducted from January to July 2025.

MAIN OUTCOMES AND MEASURES: Age-standardized incidence rates (ASIRs) as well as age-specific incidence rates per 100 000 person-years with corresponding estimated annual percentage changes (EAPCs) and 95% CIs were calculated.

RESULTS: A total of 109 787 histologically confirmed cases were identified in 95 352 unique individuals (55 891 male individuals [50.9%], 53 896 female individuals [49.1%]) 20 years or older in Denmark, receiving a first-time diagnosis of cSCC (n = 54 563), CIS (n = 31 712), or KA (n = 23 512). From 2005 to 2023, cSCC ASIRs increased (EAPC for male individuals, 2.6%; EAPC for female individuals, 3.1%), reaching 131.6 and 77.7 per 100 000 person-years in male individuals and female individuals, respectively. CIS increased markedly (EAPC, for male individuals, 6.4%; EAPC for female individuals, 5.8%), and KA declined. Stratified analyses showed distinct sex-specific anatomic patterns. Predilection sites for cSCC and CIS were the face, scalp, and neck, with particular predominance among male individuals. Female individuals exhibited higher ASIRs on the lower limbs compared with male individuals (male vs female individuals: cSCC, 7.63 vs 12.32 per 100 000; CIS, 6.21 vs 12.63 per 100 000; KA, 3.47 vs 7.20 per 100 000, respectively). KA primarily affected the extremities. Female individuals aged 40 to 59 years showed higher incidence rates than male individuals across all keratinocyte neoplasms (male vs female individuals: cSCC, 131.6 vs. 77.7 per 100 000; CIS, 89.4 vs. 78.6 per 100 000; KA 28.6 vs. 27.6 per 100 000, respectively). Trends among individuals younger than 50 years with cSCC and KA were stable.

CONCLUSIONS AND RELEVANCE: In this nationwide cohort study presenting the most comprehensive dataset of incident cSCC, CIS, and KA, with 109 787 histologically confirmed patient cases, covering nearly 2 decades and spanning across all Danish health care sectors, incidence of cSCC and CIS continued to rise, consequently affecting more people, and sex differences diminished. Stabilizing trends in individuals younger than 50 years may indicate early prevention effects. Findings of this study have the potential to influence future surveillance activities and clinical care through attention to sex, age, and anatomical site.

PMID:41604163 | DOI:10.1001/jamadermatol.2025.5700

JAMA Netw Open. 2026 Jan 2;9(1):e2555952. doi: 10.1001/jamanetworkopen.2025.55952.

ABSTRACT

IMPORTANCE: Patients with diabetes and a history of major adverse limb events (MALEs) are at an increased risk of cardiovascular and limb-related complications; however, effective glucose-lowering therapies for secondary prevention in this population are limited.

OBJECTIVE: To evaluate whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with reduced risk of MALEs and major adverse cardiovascular events (MACE) compared with dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with diabetes and prior MALEs.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, nationwide cohort study used data from the Taiwan National Health Insurance Research Database from October 2012 to December 2023. Patients with diabetes and a history of MALE who initiated GLP-1 RAs or DPP-4 inhibitors were included. MALEs were defined as chronic limb-threatening ischemia, lower limb revascularization, or nontraumatic minor and major amputation.

EXPOSURES: Initiation of GLP-1 RAs (liraglutide, dulaglutide, or semaglutide) vs DPP-4 inhibitors.

MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of lower limb revascularization and nontraumatic major and minor amputation. The secondary outcomes were MACEs (cardiovascular death, ischemic stroke, and myocardial infarction), all-cause mortality, and progression to long-term dialysis. A new-user, active-comparator design with inverse probability of treatment weighting was employed.

RESULTS: Among 17 288 patients (mean [SD] age, 70.7 [12.0] years; 10 010 male [57.9%]), 1583 initiated GLP-1 RAs and 15 705 initiated DPP-4 inhibitors. After weighting, the use of GLP-1 RAs was associated with a lower risk of MALEs (subdistribution hazard ratio [SHR], 0.90; 95% CI, 0.83-0.97), primarily due to a marked reduction in amputation (SHR, 0.86; 95% CI, 0.75-0.98). GLP-1 RAs were also associated with reduced risks of MACEs (HR, 0.62; 95% CI, 0.58-0.65), cardiovascular death (HR, 0.57; 95% CI, 0.53-0.61), all-cause mortality (HR 0.63; 95% CI, 0.60-0.66), and progression to dialysis (SHR, 0.61; 95% CI, 0.54-0.70).

CONCLUSIONS AND RELEVANCE: In this nationwide cohort study of patients with diabetes and prior MALEs, treatment with GLP-1 RAs was associated with significantly lower risks of recurrent limb events, cardiovascular events, all-cause mortality, and kidney disease progression compared with DPP-4 inhibitors. These findings support the preferential use of GLP-1 RAs for secondary prevention in this high-risk population.

PMID:41604151 | DOI:10.1001/jamanetworkopen.2025.55952

JAMA Netw Open. 2026 Jan 2;9(1):e2556012. doi: 10.1001/jamanetworkopen.2025.56012.

ABSTRACT

IMPORTANCE: The associations of adverse childhood experiences (ACEs) and adverse adulthood experiences (AAEs) with incident dementia and stroke in the Chinese population are not well understood.

OBJECTIVES: To investigate the associations of ACEs and AAEs with dementia and stroke incidence, and to examine whether depression mediates these associations.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study utilized data from the China Health and Retirement Longitudinal Study (June 2015 to December 2020). Participants aged 45 years and older with complete adverse experience data were included and were followed up for a mean (SD) of 4.89 (0.48) years for dementia and 4.84 (0.57) years for stroke. Statistical analysis was performed from August 20, 2025, to November 23, 2025.

EXPOSURES: ACEs and AAEs were assessed through a structured questionnaire, with cumulative scores calculated for both categories.

MAIN OUTCOMES AND MEASURES: Dementia was identified using a standardized cognitive battery and activities of daily living scale, while stroke was determined through self-reported physician diagnosis. Depression was evaluated using the 10-item Centre for Epidemiologic Studies Depression Scale. Cox proportional hazards regression analysis was used to explore the association of ACEs and AAEs with the risk of new-onset dementia and stroke, with results presented as hazard ratios (HRs) with 95% CIs.

RESULTS: Among 11 601 participants (mean [SD] age, 59.18 [9.41] years; 5569 male [48.0%]), 9145 (78.8%) were exposed to at least 1 ACE indicator, 4241 (36.6%) to at least 1 AAE indicator, and 3531 (30.4%) to both ACE and AAE markers. Both ACEs (HR, 1.11; 95% CI, 1.05-1.18) and AAEs (HR, 1.23; 95% CI, 1.14-1.33) were significantly associated with higher hazards of dementia during follow-up, whereas only AAEs were associated with higher hazards of stroke (HR, 1.19; 95% CI, 1.12-1.26). Latent class analysis identified a high-risk ACEs subgroup associated with incident stroke (HR, 1.33; 95% CI, 1.08-1.65). In the joint effects analyses, participants in the high-risk groups for both ACEs and AAEs exhibited higher hazards of dementia (HR, 3.28; 95% CI, 1.54-7.02) and stroke (HR, 2.50; 95% CI, 1.24-5.30). Depression mediated 34.3% of the association of ACEs with dementia (β = 0.10; 95% CI, 0.04-0.17), 20.9% of the association of AAEs with dementia (β = 0.22; 95% CI, 0.13-0.30), and 17.5% of the association of AAEs with stroke (β = 0.18; 95% CI, 0.11-0.24).

CONCLUSIONS AND RELEVANCE: In this cohort study, exposure to adverse experiences throughout life was associated with increased risks of dementia and stroke, with depression mediating these associations. These findings highlight the importance of implementing life-course interventions that address both psychological trauma and mental health to reduce the burden of neurovascular diseases.

PMID:41604149 | DOI:10.1001/jamanetworkopen.2025.56012

J Health Psychol. 2026 Jan 28:13591053251414005. doi: 10.1177/13591053251414005. Online ahead of print.

ABSTRACT

Open label placebos (OLPs) refer to the non-deceptive administration of inert treatment. This pre-registered study (AsPrediced#139837) explored the role of expectations and tailored health feedback on the OLP effect using an automated online procedure. Healthy participants (N = 293) were randomised to a 10-day course of OLP pills with veridical feedback (OLP-Feedback: N = 92), without feedback (OLP-Standard: N = 105), or to a no-treatment control (NTC: N = 96). Participants were informed the pills were inert but may enhance wellbeing. Wellbeing was assessed at baseline, day-5 and day-10. Feedback was delivered on day-5 and day-10 via interactive graphs and descriptive statistics. OLP-treatment significantly improved wellbeing (negative emotions and sleep quality), while feedback did not significantly enhance this effect. Expectations for improvement were significantly elevated among OLP-treated participants across the 10-day study. However, at the individual level, expectations only mediated OLP outcomes once treatment experience had been acquired. Results reconcile inconsistencies in the literature regarding mechanisms.

PMID:41604142 | DOI:10.1177/13591053251414005