Citations

Background Cirrhosis is associated with significant healthcare utilization, yet data about in-hospital decompensations remain sparse. Additionally, the impact of liver transplant candidacy status on resuscitation and outcomes is largely unknown. Aims We aimed to evaluate the characteristics of resuscitation events for patients with cirrhosis with acute decompensation, analyzing liver transplant candidacy and intensive care unit (ICU) transfer parameters. Methods Retrospective single-center review of adult patients with liver cirrhosis who had a rapid response team (RRT) activation during hospitalization and no prior liver transplantation. Results Patients with cirrhosis who were liver transplant candidates were more likely to be younger ( p = .003), have a higher serum total bilirubin ( p = .015), higher INR ( p < .001), and higher MELD 3.0 ( p = .006). There was no significant difference in ICU transfer ( p = .170) after RRT activation. Liver transplant candidates had a lower 30- and 60-day mortality ( p = .008, p = .014) and were less likely to have a code status discussion after decompensation ( p = .001). Lower serum albumin was associated with ICU transfer ( p = .001). Patients who transferred to the ICU were more likely to have a code status discussion within 24 h after RRT ( p = .011) without significant difference in 30- or 60-day mortality ( p = .059, p = .277). Conclusions Liver transplant candidacy in patients with cirrhosis with acute decompensation is not clearly correlated with ICU transfer. Liver transplant candidates are more likely to be younger, have higher MELD 3.0 scores, less likely to have code status discussed after RRT, and have lower 30- and 60-day mortality rates. Patients who transfer to the ICU are more likely to have a code status discussion without any significant difference in 30- or 60-day mortality.

Investment in physical space is a key strategic decision for healthcare managers. Understanding the current utilisation of clinical space is a significant input for this decision. Historically, direct observation or analysis of electronic health record (EHR) timestamps has been used to assess ambulatory space utilisation. Manual observation is prohibitively expensive, prospective and infeasible for large spaces. EHR data is limited to electronically captured workflows and to the quality of data capture. Two pilots explored the efficacy of real-time location systems (RTLS) to assess outpatient space utilisation to assist healthcare management professionals to make space allocation decisions. RTLS was shown to be viable, with accuracy that was not different from EHR-derived utilisation. RTLS had the following benefits: (a) more granular information, (b) data coverage in areas without EHR timestamps and (c) real-time assessment of utilisation. RTLS is an option for ambulatory care managers to understand the needed space for clinical operations.

Objective Acute aortic dissection type A (AADA) is a condition that affects both genders and requires urgent surgical intervention as non-operative treatment is often associated with a poor prognosis. Studies have proven that less aggressive surgical treatments influence the outcome for female patients in the fields of several diseases. The purpose of this study was to report and analyze our results in the selective cohort of female patients with AADA to detect differences in the treatment of this group of patients. Methods Between January 2000 and July 2018, 141 adult female patients with acute aortic dissection (AAD) underwent repair of the aorta in our department. A total of 75 patients received a proximal arch. replacement (group A), and 66 patients received a subtotal (replacement of the brachiocephalic trunk) and/or total arch. replacement with elephant trunk or frozen elephant trunk (group B). Results The median age in group A was 70.7 years (range 60.7–74.7 years) and in group B 66.3 years (range 55.6–71.3 years). Operation times were significantly longer in group B (total operation time: A = 286.9 min (range 225.0–341.0 min), B = 341 min (range 266.0–392 min), p = .003; cardiopulmonary bypass time: A = 189.0 min (range 139.0–138 min), B = 238 min (range 176.8–300.5 min), p < .001; circulatory arrest time: A = 27.0 min (range 21.0–37.0 min), B = 42.0 min (range 32.0–56.3 min), p < .001). There were no significant differences between the groups regarding 30-day mortality (A = 24% ( n = 18), B = 19.7% ( n = 13), p = .538) and rate of reoperation (A = 13.3% ( n = 10), B = 15.2% ( n = 10), p = .757) or the preoperative characteristics. Conclusion Our study showed no significant difference in mortality rate depending on the type of operation. Based on these results, a proximal arch. replacement should be considered as the first line of operation technique if the individual situation allows. For inexperienced clinics and surgeons in particular, we recommend limited aortic repair in patients with AADA. Finally, location of the intimal tear remains the essential factor for the evaluation of the surgical treat.

AbstractClinical recognition of primary mitochondrial disorders (PMD) is difficult due to the clinical and genetic heterogeneity. Whereas lactate has low sensitivity and specificity, in structured clinical studies growth differentiation factor 15 (GDF15) has shown promise with elevations in mitochondrial DNA (mtDNA)‐related PMD, but its specificity has been questioned. In a tertiary care hospital‐wide study, medical records were retrospectively reviewed from 418 cases where GDF15 levels were obtained by clinicians. Patients were classified into patients with PMD due to mtDNA‐related defects (mtDNA maintenance, mtDNA deletions, and mtDNA‐encoded tRNA variants), PMD due to structural defects or other nuclear causes, and in non‐mitochondrial disease. Patients with liver disease or systemic critical illness were excluded. GDF15 was assayed in a clinical laboratory with a cutoff of 750 ng/L. There were 38 mtDNA‐related PMD (GDF15 >750 pg/mL in 76%), 35 other nuclear DNA‐encoded PMD or structural subunits (31% elevated GDF15), 309 non‐mitochondrial disorders (13% elevated GDF15). Based on the highest Youden J‐index, the optimal cut‐off value to identify these target mtDNA‐related disorders was 815 pg/mL, with sensitivity 76%, specificity 88%, positive predictive value of 41% and negative predictive value of 97%. At this optimized cutoff level, mtDNA‐encoded PMD patients had elevated GDF15 in 76%, nuclear DNA‐encoded PMD in 26%, and non‐mitochondrial disorders in 11% of patients. Thus, in a real‐life clinical setting, after excluding abnormal liver function and critical illness, GDF15 had good clinical utility increasing the odds at predicting mtDNA‐related primary mitochondrial disorders 14‐fold, but not for structural or other nuclear‐encoded primary mitochondrial disorders.

Introduction Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide, with epidural hematoma (EDH) being a severe consequence. This study focuses on identifying factors predicting EDH volume changes in TBI patients and developing a machine learning (ML) model to predict EDH expansion. Methods The study includes patients with traumatic EDH between 2019 and 2021. Data were gathered from CT scans performed at the time of admission and 6 hours later, and subsequently analyzed. The data was divided into three cohorts: all cases, adults, and pediatrics. To predict EDH volume changes, we used Logistic Regression (LR), Random Forest (RF), XGBoost, and K-Nearest Neighbors (KNN) models. Data was divided into an 80% training set and a 20% test set. Through a rigorous process of parameter optimization and K-fold cross-validation, focusing on the area under the receiving operating curve (AUROC), we identified the best models in all cohorts. The best models were evaluated on the test sets, reporting AUROC, recall, precision, and accuracy using the youden index threshold. Results Results show that age, initial EDH volume, swirl sign, intra-hematoma air bleb, contusion, otorrhagia, subarachnoid hemorrhage, location, and other side extra-axial hematoma have significant effects on changing EDH volume. Based on test AUROC, the best models were RF for adults (82.4%), KNN for pediatrics (90%), and LR for all cases (81.6%). Discussion In this study, we identified key features for predicting EDH expansion as well as developing ML models. Using high sensitive models, can assist clinicians in identifying high-risk patients early. This allows for enhanced monitoring and timely intervention, improving patient outcomes by facilitating quicker decisions for follow-up imaging or treatment.

Abstract Senescent osteocytes are key contributors to age‐related bone loss and fragility; however, the impact of mechanobiological changes in these cells remains poorly understood. This study provides a novel analysis of these changes in primary osteocytes following irradiation‐induced senescence. By integrating subcellular mechanical measurements with gene expression analyses, we identified significant, time‐dependent alterations in the mechanical properties of senescent bone cells. Increases in classical markers such as SA‐β‐Gal activity and p16 Ink4a expression levels confirmed the senescence status post‐irradiation. Our key findings include a time‐dependent increase in cytoskeletal Young's modulus and altered viscoelastic properties of the plasma membrane, affecting the contractility of primary osteocytes. Additionally, we observed a significant increase in Sclerostin ( Sost ) expression 21 days post‐irradiation. These biophysical changes may impair osteocyte mechanosensation and mechanotransduction, contributing to bone fragility. This is the first study to time‐map senescence‐associated mechanical changes in the osteocyte cytoskeleton. Our findings highlight the potential of biophysical markers as indicators of cellular senescence, providing more specificity than traditional, variable biomolecular markers. We believe these results may support biomechanical stimulation as a potential therapeutic strategy to rejuvenate aging osteocytes and enhance bone health.

AbstractBackgroundCALGB 30610 trial demonstrated that once daily thoracic radiotherapy (TRT) was not superior compared to standard twice daily TRT, in patients with limited stage small cell lung cancer. Quality of life outcomes may help oncologists decide the best treatment approach.MethodsA total of 417 patients on CALGB 30610 participated in the quality‐of‐life substudy (CALGB 70702), which included the FACT Trial Outcome Index‐Lung Cancer (FACT‐L TOI), FACT‐Esophageal Cancer (FACT‐E) Eating and Swallowing Indices, ECOG Acute Esophagitis Scale, Hospital Anxiety and Depression Scale (HADS), difficulty swallowing, EQ‐5D, and treatment convenience assessment at baseline, 3, 5, 7, 12, 26, and 52 weeks after starting TRT. Primary end points included FACT‐L TOI and FACT‐E at 12 weeks. Mean changes from baseline were compared between arms using general linear mixed models.ResultsFACT‐L worsening was more in the twice daily arm at week 3 (–1.0 vs. –7.0). FACT‐L TOI worsening was less at week 3 (–2.9 vs. –7.6) and greater at week 12 (–7.6 vs. –2.8) in the once daily arm. The once daily arm had a lower EQ‐5D index worsening at 3 weeks (0.01 vs. –0.02). Increase in acute esophagitis score (1.06 vs. 2.89; p < .001) and difficulty swallowing (0.39 vs. 1.14) were greater in the twice daily arm at week 3. A total of 74.5% of patients on the once daily arm felt that treatment was convenient, compared to 67% of patients in the twice daily arm (p = .03).ConclusionsThe once daily arm had better quality‐of‐life scores earlier during treatment and was perceived to be more convenient.

Abstract The A1 domain in Von Willebrand Factor (VWF) initiates coagulation through binding to platelet glycoprotein GPIbα receptors. Von Willebrand Disease (VWD)-Mutations in A1 that either impair (type 2M) or enhance (type 2B) platelet adhesion to VWF can locally destabilize and even misfold the domain. We leveraged misfolding in the gain-of-function type 2B VWD phenotype as a target, distinct from the normal conformation. Two nuclease-resistant 2′-fluoropyrimidine RNA aptamers were selected to discriminate normal A1 domains from a type 2B V1314D A1 variant in a glycosylated A1A2A3 tri-domain VWF-fragment. Two aptamers, W9 and V1, were isolated that selectively recognize, bind, and inhibit the A1–GPIbα interaction with WT A1A2A3 and V1314D A1A2A3, respectively. These aptamers were tested against their respective recombinant targets, plasma VWF, VWF concentrates, and patient plasma with the heterozygous type 2B VWD R1306W variant using clinical assays, surface plasmon resonance and inhibition assays of platelet adhesion to recombinant A1 and A1A2A3 domains under shear stress. The specificity of W9 and V1 aptamers confirms that pathological conformations of VWD Type 2B proteins are different from normal VWF. The availability of aptamers that distinguish normal plasma-derived VWF from VWD suggests potential applicability in clinical diagnosis of severe gain-of-function phenotypes.

Abstract The aims of this review are to appraise the role of the stomach in satiation, the effects of incretin and other hormone agonists on weight loss and the role of altered gastric functions in their effects on obesity or glycaemic control. In addition to the gut in its role in enzymatic digestion and hormonal responses to nutrient ingestion, gastric motor functions include accommodation, trituration and emptying [gastric emptying (GE)] of food and elicitation of postprandial satiation and satiety. The postprandially released hormones most extensively studied and utilized therapeutically are glucagon‐like peptide 1 (GLP‐1) and glucose‐dependent insulinotropic peptide (GIP). Their mechanisms of action include stimulation of pancreatic β cells to produce insulin. However, GLP‐1 reduces glucagon and slows GE, whereas GIP increases glucagon and does not alter GE. Molecular modifications of GLP‐1 (which has a T 1/2 of 3 min) led to the development of long‐acting subcutaneous or oral pharmacological agents that have been approved for the treatment of obesity, and their effects on gastric function are documented. Other medications in development target other molecular mechanisms, including glucagon and amylin. Small‐molecule GLP‐1 receptor agonists are promising for the treatment of obesity and may also slow GE. Bariatric surgery and endoscopy increase satiation by restricting gastric size; in addition Roux‐en‐Y gastric bypass and to a lesser extent sleeve gastrectomy (but not endoscopic gastroplasty) increase postprandial circulating incretins, reducing appetite. In conclusion the stomach's function is integral to the impact of the most effective pharmacological and procedural reversal of obesity related to the incretin revolution. image