Citations

ABSTRACT Background The optimal timing for basal insulin initiation in diabetic ketoacidosis (DKA) remains unclear. British guidelines endorse early basal insulin (EBI), while the American Diabetes Association emphasises overlap duration with intravenous insulin, without mention of timing. This meta‐analysis evaluates whether EBI administration of basal insulin improves clinical outcomes in adults with DKA. Methods A systematic review and meta‐analysis were performed according to the PRISMA guidelines. Databases searched included MEDLINE, Embase, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials through December 11, 2024. Inclusion criteria included articles in the English‐language randomised controlled trials (RCTs) or observational studies evaluating EBI in adult DKA patients. Non‐human studies, conference abstracts, and case reports were excluded. The primary outcome for this study was hospital length of stay (LOS). Additional outcomes included intensive care unit (ICU) LOS, time to DKA resolution, hypoglycemia, and rebound hyperglycemia between EBI and usual care. Risk of bias was assessed using the Cochrane and Newcastle‐Ottawa tools. Grading of Recommendations Assessment, Development, and Evaluation was performed to evaluate the quality of evidence. Results From 1214 identified studies, eight (4 RCTs, 4 observational) met inclusion criteria for a total of 247 patients in the EBI group and 552 patients in the control group. No significant difference in hospital LOS was found (mean difference −11.17 h; 95% CI: −29.91 to 7.56). ICU LOS, time to DKA resolution, incidence of hypoglycemia, and rebound hyperglycemia also did not demonstrate any significant differences between groups. Significant heterogeneity existed across studies for most outcomes. All studies had a high risk of bias, and the quality of evidence was very low. Conclusion EBI did not result in significant differences in hospital LOS, ICU LOS, or time to DKA resolution; however, there were no increased adverse events with EBI. Current studies of early EBI have significant limitations. Future research should focus on developing high‐quality RCTs.

ABSTRACT Background Postoperative venous thromboembolism (VTE) is a major source of morbidity and mortality. Real‐time risk stratification for VTE is important to guide measures for thromboprophylaxis. We sought to compare the discrimination of three VTE predictive systems in classifying 90‐day postoperative VTE among cancer patients undergoing pancreas and liver surgery using administrative data. Methods We conducted a retrospective analysis of the 2001–2015 SEER‐Medicare data for patients with newly diagnosed primary pancreatic or liver malignancies who underwent surgery. The primary outcome was 90‐day postoperative VTE (including deep venous thrombosis and pulmonary embolism [PE]). We used the 2001–2010 dataset to create a new VTE predictive model using multivariable logistic regression. We then compared the discrimination of the Caprini score (adapted for claims data), the Elixhauser comorbidity score, and the new predictive model using the 2011–2015 dataset. Results Our sample included 15 479 patients (12 005 pancreas and 3474 liver surgery). Median age was 74 years (interquartile range: 69–78) and 7619 were female (49%). The overall incidence of 90‐day VTE was 10.0% (90‐day PE: 4.5%). The new VTE model included age, race, history of VTE, cancer stage, preoperative chemotherapy, and Elixhauser score. The discrimination of all predictive models was modest for both VTE ( c ‐statistic 63.0%, 59.4%, and 67.8%) and PE (61.5%, 59.7%, 65.6% for Caprini, Elixhauser, and new score respectively). Conclusions The existing tools for predicting postoperative VTE show poor performance using claims data. Future research should supplement administrative data with additional data sources to better predict patients at high risk for postoperative VTE.

ABSTRACT Encapsulation of human pluripotent stem cells (hPSC) has high relevance for biomedical applications ranging from tissue engineering to drug screening and cellular therapies. Microcapsules serve a multitude of purposes—from promoting hPSC organization into spheroids to enabling scalable differentiation in vitro and providing immunoisolation in vivo. While multiple encapsulation strategies have been reported, there is typically a tradeoff between the structural complexity of capsules and throughput of their generation. Our paper describes a novel 3D printed microfluidic encapsulation device for fabricating structurally complex microcapsules with a hydrogel shell and aqueous core at rates of up to 1825 Hz. The use of 3D printing allowed to dramatically decrease device footprint when compared to standard soft lithography‐based microfluidic encapsulation devices. Leveraging decreased footprint and the ability to arrange fluidic networks in a 3D space, we fabricated a 10‐nozzle microencapsulation device that generated microcapsules at a rate 10‐times that of the single‐nozzle device. The novel microfluidic device was used to encapsulate hPSCs, human embryonic stem cells (hESCs), and induced pluripotent stem cells (iPSCs). Hydrogel microcapsules with aqueous core promoted hPSCs aggregation into spheroids or embryoid bodies, which maintained high levels of pluripotency. Our technology enables safe and effective encapsulation of hPSCs on a scale (billions of cells) required to treat patients.

Abstract Purpose Sugammadex rapidly and effectively reverses aminosteroidal neuromuscular blocking agents and has largely replaced neostigmine in perioperative practice. Although its use is associated with faster recovery and a lower rate of residual neuromuscular blockade, clinically important limitations exist. This review summarizes the literature describing incomplete reversal, recurrence of neuromuscular blockade, adverse effects, drug interactions, and challenges in special populations, with a focus on the role of quantitative neuromuscular monitoring and pharmacist-led activities to optimize sugammadex use. Summary While sugammadex substantially reduces the risk of residual neuromuscular blockade compared to neostigmine, incomplete reversal and recurrence of neuromuscular blockade continue to occur, particularly when dosing is not guided by quantitative neuromuscular monitoring. Underdosing, redistribution of neuromuscular blocking agents, and altered pharmacokinetics can all contribute to inconsistent responses. Quantitative neuromuscular monitoring, rather than choice of reversal agent, is the main determinant of reliable neuromuscular recovery and reduced occurrence of postoperative complications. Sugammadex is associated with rare but potentially serious adverse effects, including hypersensitivity reactions and cardiovascular instability, highlighting the need for careful monitoring. Patent expiration and generic availability may expand access to sugammadex, and these limitations warrant continued attention. Conclusion Sugammadex represents a major advance in neuromuscular blockade reversal but remains an imperfect agent. Safe and effective use requires individualized dosing guided by quantitative neuromuscular monitoring and vigilance for adverse effects. Pharmacists are well positioned to lead education, dosing protocol development, and monitoring strategies that optimize patient safety while supporting adoption of quantitative neuromuscular monitoring.

Abstract The rapid progress in tumour genome sequencing has created a need for bioinformatics tools to interpret the clinical significance of detected variants. VarStack² integrates information from several publicly available resources, including the Catalogue of Somatic Mutations in Cancer (COSMIC), ClinVar, cBioPortal, UCSC Genome Browser, and ClinicalTrials.gov, CIViC and presents it through a user-friendly interface. VarStack2 simplifies the process of retrieving data, saving users significant time compared to manually navigating each database individually. Users can input a variant by specifying a gene symbol, amino acid change, and coding sequence change, with the option to search tumour-specific studies in cBioPortal alongside their primary query. Results are organized into separate sections and can be exported in CSV format for further analysis. Additionally, VarStack2 offers a smart search feature that suggests variants for the gene of interest based on its database search results. These features make VarStack2 a useful tool for scientists and clinicians by enhancing the variant interpretation process and integrating somatic variant information into workflows. VarStack² is freely available at http://varstack.brown.edu/

Abstract Background Patients with inflammatory bowel disease (IBD) receiving immunosuppressive therapies are at increased risk of vaccine-preventable diseases, including influenza. Despite recommendations for annual influenza vaccination, uptake remains suboptimal. The COVID-19 pandemic prompted a surge in telemedicine (Tele-M) use, raising concerns about its impact on vaccination rates due to reduced in-person interactions. This study aimed to assess the impact of IBD-specific Tele-M on influenza vaccine uptake and identify predictors of vaccination in patients with IBD. Methods This single-center retrospective study evaluated influenza vaccine uptake among adult patients with IBD seen between September 2021 and April 2022. Patients were categorized into two groups: Tele-M only and ≥1 in-person visit. Vaccination status was confirmed using the Wisconsin Immunization Registry. Primary outcome was influenza vaccination frequency by visit type, while secondary outcomes evaluated the impact of Tele-M on other vaccinations and predictors of influenza vaccine uptake. Results Among 547 patients, 53.2% received Tele-M only and 46.8% had ≥1 in-person visit. Influenza vaccine uptake was similar between the Tele-M only and ≥1 in-person visit groups (69.0% vs. 75.1%, respectively, p = 0.11). The uptake of pneumococcal, hepatitis B, and zoster vaccines was also comparable. Predictors of higher influenza vaccine uptake included age ≥65, female sex, receipt of ≥ 3 COVID-19 vaccines, and previous influenza vaccination. Conclusions IBD-specific Tele-M did not adversely affect influenza vaccine uptake among patients with IBD. These findings highlight the importance of ensuring vaccination compliance irrespective of healthcare delivery modes. Collaboration among healthcare providers is crucial to improve vaccination rates in patients with IBD.

Introduction: The biomechanical role of the dorsal scaphotriquetral ligament (DSTL) ligament in scapholunate (SL) stability remains debated. We assessed DSTL contribution using a cadaveric sectioning model. Methods: Twenty-four wrists underwent sequential sectioning: none (phase 0), palmar/proximal scapholunate interosseous ligament (SLIOL) (phase 1), dorsal SLIOL (phase 2), superficial dorsal intercarpal ligament (DICL) (phase 3) and DSTL (phase 4). Under axial loading (60 N; cyclic 60–200 N) and wrist motion, the SL gap and carpal angles, and a CT-derived dorsal instability scaphoid angle (DISA) were measured. Results: Phase 1 produced no significant instability. Dorsal SLIOL sectioning (phase 2) initiated dynamic instability, with increased SL gap and angles under load and dorsal scaphoid translation, but no resting dorsal intercalated segment instability (DISI). Sectioning the superficial DICL fascicle (phase 3) did not add instability. DSTL sectioning (phase 4) produced the largest changes, with marked SL diastasis, increased angles and DISA, and DISI at rest and under load. Conclusion: Dorsal SLIOL sectioning produced load-dependent (dynamic) SL instability, whereas subsequent DSTL sectioning was associated with progression to static instability, supporting the DSTL as an important dorsal restraint. The DISA may provide an additional CT-based measure of dorsal scaphoid subluxation; however, clinical validation is required.

Abstract Mechanical properties of biological tissues vary across spatial scales, yet radiomics typically relies on fixed, heuristic choices for neighbourhood size, kernel geometry, and spectral content - choices that can silently reshape the feature space before any modelling begins. We introduce a label-free, information-theoretic framework for selecting extraction parameters in multi-frequency MRE radiomics. For each configuration θ - neighbourhood radius r, kernel geometry k (sphere or shell), and frequency subset f - we extract a radiomics feature matrix and score it using an objective J(θ) that integrates distributional richness (Shannon entropy), cross-frequency coherence (canonical correlation), inter-feature redundancy (Spearman correlation), and bootstrap stability. We evaluate 121 configurations per tissue in multi-frequency MRE (30-60 Hz) of human brain, liver, and a calibrated phantom, and test robustness using 10,000 Dirichlet-sampled objective weightings. Across tissues, neighbourhood aggregation is consistently preferred over voxel-wise extraction, outperforming the no-neighbourhood baseline in 98.4-100% of weightings. External validation in 100 independent brain scans acquired with a different protocol and wider frequency range (20-90 Hz) confirms a reproducible mesoscopic plateau at r = 3-5 (9-15 mm), with a modal optimum at r = 4; omitting neighbourhood analysis reduces J(θ) by 38% relative to each subject’s optimum. Frequency-subset preferences replicate across datasets, with lower frequencies most frequently selected for brain. By turning ad hoc extraction choices into an outcome-free optimisation step, this framework improves reproducibility, reduces sensitivity to heuristic parameter choices, and generalises across acquisition protocols and imaging sites.

Abstract Left atrial enlargement is a well-recognized marker of adverse cardiovascular outcomes, but its impact on early morbidity and mortality after valve replacement remains uncertain. We retrospectively reviewed 422 patients who underwent aortic and/or mitral valve replacement (MVR) for rheumatic heart disease at X between 2004 and 2022. Preoperative left atrial diameter index (LADI) was measured, and patients were classified as normal (<2.3 cm/m2) or abnormal (≥2.3 cm/m2). Clinical, operative, and postoperative outcomes were compared. The primary endpoint was 30-day all-cause mortality; secondary endpoints included postoperative atrial fibrillation (POAF), neurological events, renal impairment, re-exploration for bleeding, and intraoperative pacing wire requirement. Nearly half of patients (48.8%) had abnormal LADI. Patients with enlarged atria were more often female, had smaller body size, and were significantly more likely to undergo MVR (42.7% versus 18.1%, p < 0.001). Abnormal LADI was strongly associated with POAF (16.0% versus 7.4%, p = 0.006) and intraoperative pacing wire insertion (38.3% versus 23.5%, p = 0.001). Multivariate analysis confirmed severe LADI as an independent predictor of POAF (OR 3.91, p = 0.001) and pacing requirements (OR 2.31, p = 0.004). No significant differences were observed in 30-day mortality, stroke/transient ischemic attack, renal dysfunction, or bleeding complications. Preoperative LADI is an independent predictor of postoperative arrhythmic complications and pacing needs after valve replacement, but not early mortality. Incorporating LADI into preoperative risk assessment may improve rhythm surveillance and perioperative planning. Future prospective studies should evaluate its long-term prognostic value and role in reverse remodeling after surgery.