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Introduction: Robot-assisted radical prostatectomy (RARP) has become a popular surgical approach for localized prostate cancer due to its favorable oncological and functional outcomes, as well as lower morbidity. In cases of intermediate- and high-risk prostate cancer, bilateral pelvic lymphadenectomy (PLND) is recommended as an adjunct to RARP (1-3). Despite its benefits, PLND can lead to surgical complications, with postoperative lymphocele formation being the most common. Most postoperative lymphoceles are clinically insignificant with variable incidence, reaching up to 60% of cases 4. However, a small percentage of patients 2-8% may experience symptomatic lymphoceles (SL), which can cause significant morbidity (4, 5)., Surgical Technique: We perform our RARP technique with our standard approach in all patients (6). After vesicourethral anastomosis a modified PF created to prevent symptomatic lymphocele. We start by suturing the peritoneal fold on the right side, medially to the vas deferens, followed by a similar stitch on the left side to approximate the edges in the midline. A running suture bunches the bladder peritoneum from both sides, passing through the pubic bone periosteum to secure it in place (7). This approach keeps the lateral pelvic gutters open for lymphatic drainage, while allowing fluid drainage from the true pelvis into the abdomen. A pelvic ultrasound was done for all patients at 6 weeks post operative, and additional clinical follow-up was carried out at 3 months following surgery., Considerations: We have demonstrated a modified technique of peritoneal flap (PBFB) with an initial decrease in postoperative symptomatic lymphoceles, the technique is feasible, safe, does not add significant morbidity, and does not require a learning curve., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Ageing-related muscle atrophy/sarcopenia is the most common type of muscle impairment that affects the quality of life. In the current study, we examined the effect of a functional food mixture of amla, turmeric, black pepper, cinnamon, and ginger on D-galactose-induced muscle alterations in rats. Wistar rats were randomly divided into 3 groups: Control (C), D-galactose (G), and D-galactose + functional food mixture intervention (G+I). Rats in group-G and -G+I were injected with D-galactose (300 mg/Kg/day) for 90 days. After three months of the experimental period, the rats were sacrificed to collect gastrocnemius muscle. Group-G rats showed elevated levels of inflammatory cytokines (TNFα and NF-kB), atrogenes (Atrogin-1 and MuRF1), decreased insulin/IGF1 signaling (decreased AKT phosphorylation), altered mitochondrial dynamics (increased fission and decreased fusion proteins), increased apoptotic mediators (Bax/Bcl2, and caspase-3) and decreased muscle cell cross-sectional area when compared with group-C (p<0.05). Interestingly, supplementation with the functional food mixture prevented galactose-induced alterations in the muscle. The observed anti-inflammatory, insulin-sensitizing, mitochondria-protective, and antiapoptotic effects of the functional food could be the underlying mechanisms in displaying positive effects against galactose-induced muscle atrophy and, hence, may be useful for the prevention of age-related muscle disorders.

Objectives: This study aimed to train a 3D U-Net convolutional neural network (CNN) for mandible and lower dentition segmentation from cone-beam computed tomography (CBCT) scans., Methods: In an ambispective cross-sectional design, CBCT scans from two hospitals (2009-2019 and 2021-2022) constituted an internal dataset and external validation set, respectively. Manual segmentation informed CNN training, and evaluations employed Dice similarity coefficient (DSC) for volumetric accuracy. A blinded oral maxillofacial surgeon performed qualitative grading of CBCT scans and object meshes. Statistical analyses included independent t-tests and ANOVA tests to compare DSC across patient subgroups of gender, race, body mass index (BMI), test dataset used, age, and degree of metal artifact. Tests were powered for a minimum detectable difference in DSC of 0.025, with alpha of 0.05 and power level of 0.8., Results: 648 CBCT scans from 490 patients were included in the study. The CNN achieved high accuracy (average DSC: 0.945 internal, 0.940 external). No DSC differences were observed between test set used, gender, BMI, and race. Significant differences in DSC were identified based on age group and the degree of metal artifact. The majority (80%) of object meshes produced by both manual and automatic segmentation were rated as acceptable or higher quality., Conclusion: We developed a model for automatic mandible and lower dentition segmentation from CBCT scans in a demographically diverse cohort including a high degree of metal artifacts. The model demonstrated good accuracy on internal and external test sets, with majority acceptable quality from a clinical grader., (© 2024. The Author(s) under exclusive licence to Japanese Society for Oral and Maxillofacial Radiology.)

An electrocardiogram of an uncommon congenital heart disease is presented to highlight the unique findings in diagnosis with its clinical implications and predictive value., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: In a patient with elevated thyroid stimulating hormone (TSH, >50 µIU/ml) with sellar mass, it is crucial to differentiate isolated pituitary hyperplasia (IPH) from primary hypothyroidism coexisting with nonfunctioning pituitary adenoma (PHCNFPA) pre-operatively to avoid unwarranted surgery in the former condition. Here, we describe patients having pituitary mass/enlargement with markedly elevated TSH (>50 µIU/ml) and attempt to find the differentiating features between IPH and PHCNFPA., Methods: This is a retrospective study conducted at a tertiary care center. Case records of patients presenting between January 2020 and December 2022 with elevated TSH (>50 µIU/ml) for whom magnetic resonance imaging (MRI) of the sella was available were reviewed. Demographic details, symptomatology, clinical examination findings, thyroid function tests, data on pituitary hormonal excess and deficiencies, MRI findings, and details regarding levothyroxine supplementation were noted. Based on the final diagnosis, the patients were categorized into two groups: PHCNFPA and IPH., Results: Five and 11 patients were diagnosed with PHCNFPA and IPH, respectively. The median (IQR) age at presentation of patients with PHCNFPA was significantly higher than that of IPH patients [37 (28-60.5) vs. 21 (10-21.5) years, p: 0.002]. A longer duration of hypothyroid symptoms was noted in the IPH group whereas visual field defects and corticotropin deficiency were more frequent and the pituitary lesion size was greater in PHCNFPA. Thyroid function tests were not different between the two groups. The pituitary enlargement in IPH was initially an increase in pituitary height that progressed to symmetrical nipple-, dome- or tent-shaped enlargement. Besides this characteristic enlargement pattern, isointense appearance on T1-weighted and T2-weighted images, homogeneous contrast enhancement, and prompt regression of pituitary lesion with levothyroxine replacement were characteristic of IPH whereas heterogeneous enhancement, cystic/hemorrhagic change, and ≥Knosp III invasion were characteristic of PHCNFPA. Peripheral rim enhancement and Knosp I-II parasellar extension were not uncommon in patients with IPH and did not distinguish it from PHCNFPA., Conclusions: The present study reports the radiological evolution of IPH and a unique series of PHCNFPA along with the distinguishing characteristics between them., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: SARS-CoV-2 vaccines are safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. This study was performed to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population., Methods and Findings: A retrospective clinical cohort study was performed utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. The primary outcome was the incidence and time to the first positive SARS-CoV-2 molecular test in the Omicron predominant era. Multivariable Cox modeling analyses to determine the hazard of SARS-CoV-2 infection were stratified by calendar time (Period 1: January 1 -June 30, 2022; Period 2: July 1 -December 31, 2022) due to violations in the proportional hazards assumption. In total, 133,191 patients were analyzed. During Period 1, having 3+ comorbidities was associated with increased hazard for breakthrough (HR = 1.16 CI 1.08-1.26). During Period 2 of the study, having 2 comorbidities (HR = 1.45 95% CI 1.26-1.67) and having 3+ comorbidities (HR 1.73, 95% CI 1.51-1.97) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in Period 1 of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period., Conclusions: Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age plays an important role in breakthrough infection with the highest incidence among young adults, which may be due to age-related behavioral factors. These findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Moreno Echevarria et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Pigeonpea ( Cajanus cajan ) is one of the important grain legume crops cultivated in the semi-arid tropics, playing a crucial role in the economic well-being of subsistence farmers. India is the major producer of pigeonpea, accounting for over 75% of the world's production. Sterility mosaic disease (SMD), caused by Pigeonpea sterility mosaic virus (PPSMV) and transmitted by the eriophyid mite ( Aceria cajani ), is a major constraint to pigeonpea cultivation in the Indian subcontinent, leading to potential yield losses of up to 100%. The recent characterization of another Emaravirus associated with SMD has further complicated the etiology of this challenging viral disease. This review focuses on critical areas, including the current status of the disease, transmission and host-range, rapid phenotyping techniques, as well as available disease management strategies. The review concludes with insights into the future prospects, offering an overview and direction for further research and management strategies.

Background: Systemic immunomodulatory agents are indicated in the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. Perioperative use of these medications may increase the risk of surgical site infection (SSI) and complication., Objective: To evaluate the risk of SSI and complication in patients with chronic autoimmune inflammatory disease receiving immunomodulatory agents (tumor necrosis factor-alfa [TNF-α] inhibitors, interleukin [IL] 12/23 inhibitor, IL-17 inhibitors, IL-23 inhibitors, cytotoxic T-lymphocyte-associated antigen-4 costimulator, phosphodiesterase-4 inhibitor, Janus kinase inhibitors, tyrosine kinase 2 inhibitor, cyclosporine (CsA), and methotrexate [MTX]) undergoing surgery., Methods: We performed a search of the MEDLINE PubMed database of patients with chronic autoimmune inflammatory disease on immune therapy undergoing surgery., Results: We examined 48 new or previously unreviewed studies; the majority were retrospective studies in patients with rheumatoid arthritis and inflammatory bowel disease., Conclusion: For low-risk procedures, TNF-α inhibitors, IL-17 inhibitors, IL-23 inhibitors, ustekinumab, abatacept, MTX, CsA, and apremilast can safely be continued. For intermediate- and high-risk surgery, MTX, CsA, apremilast, abatacept, IL-17 inhibitors, IL-23 inhibitors, and ustekinumab are likely safe to continue; however, a case-by-case approach is advised. Acitretin can be continued for any surgery. There is insufficient evidence to make firm recommendations on tofacitinib, upadacitinib, and deucravacitinib., Competing Interests: Conflicts of interest Dr Feldman has received research, speaking and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alvotech, vTv Therapeutics, Bristol Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, Sun Pharma, Almirall, Galderma, LEO Pharma, Mylan, Celgene, Ortho Dermatology, Menlo, Merck & Co, Qurient, Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Teladoc, BMS, Ono, Micreos, Eurofins, Informa, UpToDate, and the National Psoriasis Foundation and is a founder and part owner of Causa Research and holds stock in Sensal Health. Dr Wu is or has been an investigator, consultant, or speaker for AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, DermTech, Dr. Reddy’s Laboratories, Eli Lilly, EPI Health, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Pfizer, Regeneron, Samsung Bioepis, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, and Zerigo Health. Dr Hsu has served on the advisory board for Boehringer Ingelheim, LEO Pharma, and Sanofi and has served on the registries/clinical trials for CorEvitas, PROSE, Argenx, and Cabaletta. Dr Armstrong has served as a research investigator, scientific adviser, and/or speaker to AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, BI, BMS, EPI, Incyte, Leo, UCB, Janssen, Lilly, Mindera, Nimbus, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron, and Pfizer. Dr Wallace has served as a research investigator, scientific adviser, and/or speaker to Pfizer, Target RWE, Kyowa, Amgen, Arcutis, and Argenx. Dr Lee has served as a research investigator, scientific adviser, and/or speaker to Eli Lilly, Sanofi, Regeneron, Pfizer, Trevi Therapeutics, AbbVie, Mayne Pharmaceuticals, Incyte Corp, Castle Creek, Pyramid Bioscience, Amyrt, Krystal Biotech, Arcutis, Celgene, Target Pharma, Amgen, Novartis, UCB, Galderma, Kiniksa, Avita, Janssen, MoonLake Pharmaceuticals, and Timber Pharmaceuticals. Dr Merola is a consultant and/or investigator for Amgen, Bristol Myers Squibb, AbbVie, Dermavant, Eli Lilly, Incyte, Novartis, Janssen, UCB, Sanofi Regeneron, Sun Pharma, Biogen, Pfizer, and LEO Pharma. Dr Schwartzman has served as a speaker and/or consultant to AbbVie, Janssen, Lilly, Pfizer, UCB, Myriad, Novartis, Sanofi/Regeneron, Stelexis, Jubilant, and Teijin and has served as a board member to the National Psoriasis Foundation. Dr Gladman has received consulting fees from AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB and has received research support from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. Dr Liu has served as a research investigator, scientific adviser, and/or speaker to for AbbVie, Janssen, Lilly, Sanofi Regeneron, Arcutis, Dermavant, Pfizer, Bristol Myers Squibb, UCB, Incyte, Amgen, and Evelo. Dr Koo has served on the advisory board/consultant for AbbVie, Arcutis, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Castle, Dermavant, Incyte, Janssen, Eli Lilly, EPI, Leo, Novartis, Ortho Dermatologics/Valeant, Pfizer, Regeneron/Sanofi, Sun Pharma, and UCB. Dr Hawkes has served on the advisory board/consultant for AbbVie, Arcutis, Boehringer Ingelheim, BMS, Janssen, LearnSkin, LEO, Lilly, Novartis, Pfizer, Regeneron-Sanofi Genzyme, and UCB, has served on the medical/scientific board for the National Psoriasis Foundation and International Psoriasis Council (IPC), and has stock ownership/equity in Regeneron Pharmaceuticals. Dr Reddy has served on the advisory board/consultant UCB, Novartis, Fresenius, Amgen, AbbVie, Janssen, and Pfizer. Dr Prussick has served as a scientific adviser and/or speaker to of Amgen, Janssen, AbbVie, and Novartis and has served as a board member to the National Psoriasis Foundation. Dr Yamauchi has served as a research investigator, scientific adviser, and/or speaker to AbbVie, Amgen, Lilly, Janssen, Sun Pharma, BMS, UCB, Ortho Dermatologics, and Novartis. Dr Lewitt has received grants/research support from Novan, Galderma, Leo, Lilly, DermTech, and Amgen and has served as a speaker’s bureau/consultant/advisory board for AbbVie, Janssen, Lilly, Galderma, Pfizer, UCB, Ortho Dermatologics, Dermavant, and Bristol Myers Squibb. Dr Soung has served as a research investigator, scientific adviser, and/or speaker to Celgene, Amgen, Eli Lilly, AbbVie, Pfizer, Ortho Dermatologics, National Psoriasis Foundation (non-profit), LEO, Novartis, Regeneron/Sanofi, UCB, Janssen, Kyowa Kirin, Dermavant, Bristol Myers Squibb, Arcutis, KoBioLabs, and Castle Biosciences. Dr Weinberg has served as a speaker for AbbVie, Dermavant, Lilly, Janssen, BMS, Amgen, and UCB and has received research grants from Arcutis, Dermavant, AbbVie, UCB, Janssen, and Lilly. Dr Lebwohl is an employee of Mount Sinai, has received research funds from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Inozyme, Janssen Research & Development, LLC, Novartis, Ortho Dermatologics, Regeneron, and UCB, Inc, and is a consultant for AnaptysBio, Arcutis, Inc, Arena Pharmaceuticals, Aristea Therapeutics, Avotres Therapeutics, BioMX, Boehringer Ingelheim, Brickell Biotech, Cara Therapeutics, Castle Biosciences, CorEvitas, Dermavant Sciences, Evommune, Inc, Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Hexima Ltd, Incyte, Meiji Seika Pharma, Mindera, National Society of Cutaneous Medicine, New York College of Podiatric Medicine, Pfizer, Seanergy, SUN Pharma, Verrica, and Vial. Dr Glick has served as a research investigator, scientific adviser, and/or speaker to AbbVie, AstraZeneca, Amgen, Janssen, Galderma, Sun Pharma, LEO Pharma, Lilly, Novartis, Dermavant Sciences, Incyte, EPI/Novan, BMS, Nimbus Lakshmi, Cara Therapeutics, Dermira, Sanofi/Genzyme, Regeneron, Pfizer, ChemoCentryx, Ortho Dermatologics, UCB, Brickell, Biotech, CorEvitas Registry PSO, CorEvitas Registry AD, PROSE Registry for AD. Dr Kircik has served as a research investigator, scientific adviser, board member, and/or speaker to Abbott Laboratories, AbbVie, Allergan, Inc, Almirall, Amgen, Inc, Arcutis, Biogen-Idec, BMS, Boehringer Ingelheim, Breckinridge Pharma, Celgene, Centocor, Inc, Cellceutix, Cipher, Combinatrix, Connetics Corporation, Coria, Dermavant, Dermira, Dow Pharmaceutical Sciences, Inc, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Genentech, Inc, GlaxoSmithKline, PLC, Idera, Johnson & Johnson, Leo, Maruho, Merck, Medicis Pharmaceutical Corp, Novartis AG, Promius, PharmaDerm, Pfizer, Serono (Merck Serono International SA), Stiefel Laboratories, Inc, Sun Pharma, Taro, UCB, Valeant Pharmaceuticals Intl, and XenoPort. Dr Desai has served on the Medical Board of the National Psoriasis Foundation and holds multiple other leadership positions in dermatologic organizations, and has served as a researcher and/or consultant for Pfizer, Lilly, AbbVie, Bristol Myers Squibb, Galderma, and other organizations. Drs James and Zaino and Author Rosenberg have no conflicts of interest to declare., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Early-stage nonalcoholic fatty liver disease (NAFLD) is a silent condition, with most cases going undiagnosed, potentially progressing to liver cirrhosis and cancer. A non-invasive and cost-effective detection method for early-stage NAFLD detection is a public health priority but challenging. In this study, an adhesive, soft on-skin sensor with low electrode-skin contact impedance for early-stage NAFLD detection is fabricated. A method is developed to synthesize platinum nanoparticles and reduced graphene quantum dots onto the on-skin sensor to reduce electrode-skin contact impedance by increasing double-layer capacitance, thereby enhancing detection accuracy. Furthermore, an attention-based deep learning algorithm is introduced to differentiate impedance signals associated with early-stage NAFLD in high-fat-diet-fed low-density lipoprotein receptor knockout (Ldlr -/- ) mice compared to healthy controls. The integration of an adhesive, soft on-skin sensor with low electrode-skin contact impedance and the attention-based deep learning algorithm significantly enhances the detection accuracy for early-stage NAFLD, achieving a rate above 97.5% with an area under the receiver operating characteristic curve (AUC) of 1.0. The findings present a non-invasive approach for early-stage NAFLD detection and display a strategy for improved early detection through on-skin electronics and deep learning., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: Epilepsy surgery is an underutilized resource for children with drug-resistant epilepsy. Palliative and definitive surgical options can reduce seizure burden and improve quality of life. Palliative epilepsy surgery is often seen as a "last resort" compared to definitive surgical options. We compare patient characteristics between palliative and definitive epilepsy surgical patients and present palliative surgical outcomes from the Pediatric Epilepsy Research Consortium surgical database., Methods: The Pediatric Epilepsy Research Consortium Epilepsy Surgery database is a prospective registry of patients aged 0-18 years undergoing evaluation for epilepsy surgery at 20 pediatric epilepsy centers. We included all children with completed surgical therapy characterized as definitive or palliative. Demographics, epilepsy type, age of onset, age at referral, etiology of epilepsy, treatment history, time-to-referral/evaluation, number of failed anti-seizure medications (ASMs), imaging results, type of surgery, and postoperative outcome were acquired., Results: Six hundred forty patients undergoing epilepsy surgery were identified. Patients undergoing palliative procedures were younger at seizure onset (median: 2.1 vs 4 years, P= 0.0008), failed more ASM trials before referral for presurgical evaluation (P=<0.0001), and had longer duration of epilepsy before referral for surgery (P=<0.0001). During presurgical evaluation, patients undergoing palliative surgery had shorter median duration of video-EEG data collected (P=0.007) but number of cases where ictal data were acquired was similar between groups. The most commonly performed palliative procedure was corpus callosotmy (31%), followed by lobectomy (21%) and neuromodulation (82% responsive neurostimulation vs 18% deep brain stimulation). Palliative patients were further categorized into traditionally palliative procedures vs traditionally definitive procedures. The majority of palliative patients had 50% reduction or better in seizure burden. Seizure free outcomes were significantly higher among those with traditional definitive surgeries, 41% (95% confidence interval: 26% to 57%) compared with traditional palliative surgeries and 9% (95% confidence interval: 2% to 17%). Rate of seizure freedom was 46% at 24 months or greater of follow-up in the traditional definitive group., Conclusions: Patients receiving palliative epilepsy surgery trialed more ASMs, were referred later after becoming drug resistant, and had longer gaps between drug resistance and epilepsy surgery compared with patients undergoing definitive epilepsy surgery. The extent of surgical evaluation is impacted if surgery is thought to be palliative. A majority of palliative surgery patients achieved >50% seizure reduction at follow-up, both in groups that received traditionally palliative and traditionally definitive surgical procedures. Palliative surgical patients can achieve greater seizure control and should be referred to an epilepsy surgery center promptly after failing two appropriate anti-seizure medications., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Meniscal tears are common knee injuries with limited endogenous healing capacity. This study aimed to investigate the association between the timing and administration of preoperative intra-articular corticosteroid injections (CSIs) and the risk of subsequent meniscectomy following meniscus repair., Methods: Using a national insurance claims database, patients aged 18-40 years undergoing meniscus repair within six months of tear diagnosis were studied. Patients were categorized based on whether they received preoperative CSIs within three intervals prior to repair. Multivariable logistic regression was used to analyze the risk of follow-up meniscectomy while controlling for various patient-related variables., Results: Among 5,390 patients meeting inclusion criteria, 201 received preoperative CSIs. The CSI group was older and had higher rates of diabetes, obesity, and knee osteoarthritis. The overall rate of follow-up meniscectomy did not differ between groups. However, CSIs performed within one month prior to repair were associated with significantly higher odds of subsequent meniscectomy compared to CSIs performed between three and six months prior. Obesity, tobacco use, and knee osteoarthritis were also independently associated with higher risk, while increasing age was associated with lower risk., Conclusion: The study highlights an increased risk of repair failure requiring follow-up meniscectomy for patients receiving intra-articular CSIs within one month prior to meniscus repair. These findings suggest caution when considering CSIs as a treatment option for patients scheduled for meniscus repair. Further research is needed to establish optimal timing guidelines for CSIs in relation to meniscus repair and to understand the underlying mechanisms.

Background: This study sought to measure hospital variability in adoption of balanced transfusion following the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) guidelines. We hypothesized hospital adoption rates of balanced transfusion would be low, and vary significantly among hospitals after controlling for patient, injury and hospital characteristics., Study Design and Methods: This was an observational cohort study of injured adult patients (≥16 years) in Trauma Quality Improvement Program hospitals 2016-2021. Inclusion criteria were hypotensive patients receiving one transfusion of packed red blood cells, fresh frozen plasma, platelets, or cryoprecipitate. Balanced transfusion was defined as ≥1 ratio of plasma to packed red blood cells or platelets to packed red blood cells or whole blood use at 4 hours. Hierarchical multivariable logistic regression quantified residual hospital-level variability in balanced transfusion rates after adjusting for patient and hospital characteristics., Results: Among 172,457 injured patients who received transfusions, 30,386 (17.6%) underwent balanced transfusion. Patient-level balanced transfusion rates were 11% in 2016, rose to 14.0% in 2019, and jumped up once whole blood transfusions were measured to 24.0% in 2020 and to 25.9% in 2021. Approximately 26% of the variability in balanced transfusion rates was attributable to the hospital. Verified level I hospitals had a 2.09 increased adjusted odds of balanced transfusion (95% CI 1.88-2.21) compared to nonverified hospitals. University teaching status had a 1.29 increased adjusted odds of balanced transfusion (95% CI 1.08-1.54) compared with community hospitals. Overall, 150 (23.5%) hospitals were high outliers (high performing) in balanced transfusion adoption and 124 (19.4%) hospitals were low outliers., Conclusion: There was significant variability in hospital adoption of balanced transfusion., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Pulmonary embolism (PE) is a well-recognised complication of COVID-19 infection, and chronic thromboembolic pulmonary disease with and without pulmonary hypertension (CTEPD/CTEPH) are potential life-limiting consequences. At present the burden of CTEPD/CTEPH is unclear and optimal and cost-effective screening strategies yet to be established., Methods: We evaluated the CTEPD/CTEPH referral rate to the UK national multidisciplinary team (MDT) during the 2017-2022 period to establish the national incidence of CTEPD/CTEPH potentially attributable to COVID-19-associated PE with historical comparator years. All individual cases of suspected CTEPH were reviewed by the MDT for evidence of associated COVID-19. In a separate multicentre cohort, the risk of developing CTEPH following hospitalisation with COVID-19 was calculated using simple clinical parameters at a median of 5 months post hospital discharge according to existing risk scores using symptoms, ECG and NT pro-BNP., Results: By the second year of the pandemic, CTEPH diagnoses had returned to the pre-pandemic baseline (23.1 versus 27.8 cases per month, p=0.252). Of 334 confirmed CTEPD/CTEPH cases, 4 (1.2%) patients were identified to have CTEPH potentially associated with COVID-19 PE, and a further 3 (0.9%) CTEPD without PH. Of 1094 patients (mean age 58 years, 60.4% male) hospitalised with COVID-19 screened across the UK, 11 (1.0%) were at high risk of CTEPH at follow-up, none of whom had a diagnosis of CTEPH made at the national MDT., Conclusion: A-priori risk of developing CTEPH following COVID-19-related hospitalisation is low. Simple risk scoring is a potentially effective way of screening patients for further investigation., (Copyright ©The authors 2024.)

Purpose: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence., Methods: Plasma samples, clinical data, and imaging results were collected from 319 patients. A tumor-informed ctDNA assay was used for analysis. Patients were divided into discovery (167 patients) and validation (152 patients) cohorts. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed., Results: ctDNA showed high sensitivity, 95% (discovery; 95% CI, 87 to 99) and 94% (validation; 95% CI, 85 to 98), for detecting disease at enrollment, with corresponding specificities of 90% (95% CI, 82 to 95) and 86% (95% CI, 77 to 93). A positive ctDNA during surveillance indicated increased recurrence risk, with hazard ratios (HRs) of 6.8 (discovery; 95% CI, 2.9 to 16) and 20 (validation; 95% CI, 8.3 to 50). The PPV for clinical recurrence at 1 year after a positive ctDNA test was 69% (discovery; 95% CI, 32 to 91) and 94% (validation; 95% CI, 71 to 100), respectively. The NPV at 135 days after a negative ctDNA test was 94% (discovery; 95% CI, 90 to 97) and 93% (validation; 95% CI, 89 to 97), respectively. Patients positive for ctDNA within 4 months after treatment had higher rates of recurrence, with 1-year rates of 74% versus 21% (adjusted HR, 7.4 [95% CI, 2.7 to 20])., Conclusion: ctDNA testing exhibited high prognostic accuracy in detecting MCC recurrence, suggesting its potential to reduce frequent surveillance imaging. ctDNA also identifies high-risk patients who need more frequent imaging and may be best suited for adjuvant therapy trials.

Introduction: Various Machine Learning (ML) models have been used to predict sepsis-associated mortality. We conducted a systematic review to evaluate the methodologies employed in studies to predict mortality among patients with sepsis., Methods: Following a pre-established protocol registered at the International Prospective Register of Systematic Reviews, we performed a comprehensive search of databases from inception to February 2024. We included peer-reviewed articles reporting predicting mortality in critically ill adult patients with sepsis., Results: Among the 1822 articles, 31 were included, involving 1,477,200 adult patients with sepsis. Nineteen studies had a high risk of bias. Among the diverse ML models, Logistic regression and eXtreme Gradient Boosting were the most frequently used, in 22 and 16 studies, respectively. Nine studies performed internal and external validation. Compared with conventional scoring systems such as SOFA, the ML models showed slightly higher performance in predicting mortality (AUROC ranges: 0.62-0.90 vs. 0.47-0.86)., Conclusions: ML models demonstrate a modest improvement in predicting sepsis-associated mortality. The certainty of these findings remains low due to the high risk of bias and significant heterogeneity. Studies should include comprehensive methodological details on calibration and hyperparameter selection, adopt a standardized definition of sepsis, and conduct multicenter prospective designs along with external validations., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: We evaluated the efficacy of risk-based, protocol-driven management versus (vs) usual management after elective major cancer surgery to reduce 30-day rates of postoperative death or serious complications (DSC) ., Summary Background Data: Major cancer surgery is associated with significant perioperative risks which result in worse long-term outcomes., Methods: Adults scheduled for elective major cancer surgery were stratified/randomized to risk-based escalating levels of care, monitoring, and co-management vs usual management. The primary study outcome was 30-day rate of DSC. Additional outcomes included complications, adverse events, health care utilization, health-related quality of life (HRQOL), and disease-free and overall survival (DFS and OS)., Results: Between August 2014 and June 2020, 1529 patients were enrolled and randomly allocated to the study arms; 738 patients in the Intervention Arm and 732 patients in the Control Arm were eligible for analysis. 30-day rate of DSC with the intervention was 15.0% (95% CI, 12.5-17.6%) vs 14.1%, (95% CI, 11.6-16.6%) with usual management (P=0.65). There were no differences in 30-day rates of complications or adverse events (including return to the operating room); postoperative length of stay; rate of discharge to home; or 30, 60, or 90-day HRQOL or rates of hospital readmission or receipt of anti-neoplastic therapy between the study arms. At median follow-up of 48 months, OS (P=0.57) and DFS (P=0.91) were similar., Conclusions: Risk-based, protocol-driven management did not reduce 30-day rate of DSC after elective major cancer surgery compared to usual management, nor improve postoperative health care utilization, HRQOL, or cancer outcomes. Trials are needed to identify cost-effective, tailored perioperative strategies to optimize outcomes after major cancer surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hospital-onset bacteraemia and fungaemia (HOB) is being explored as a surveillance and quality metric. The objectives of the current study were to determine sources and preventability of HOB in hospitalised patients in the USA and to identify factors associated with perceived preventability., Methods: We conducted a cross-sectional study of HOB events at 10 academic and three community hospitals using structured chart review. HOB was defined as a blood culture on or after hospital day 4 with growth of one or more bacterial or fungal organisms. HOB events were stratified by commensal and non-commensal organisms. Medical resident physicians, infectious disease fellows or infection preventionists reviewed charts to determine HOB source, and infectious disease physicians with training in infection prevention/hospital epidemiology rated preventability from 1 to 6 (1=definitely preventable to 6=definitely not preventable) using a structured guide. Ratings of 1-3 were collectively considered 'potentially preventable' and 4-6 'potentially not preventable'., Results: Among 1789 HOB events with non-commensal organisms, gastrointestinal (including neutropenic translocation) (35%) and endovascular (32%) were the most common sources. Overall, 636/1789 (36%) non-commensal and 238/320 (74%) commensal HOB events were rated potentially preventable. In logistic regression analysis among non-commensal HOB events, events attributed to intravascular catheter-related infection, indwelling urinary catheter-related infection and surgical site infection had higher odds of being rated preventable while events with neutropenia, immunosuppression, gastrointestinal sources, polymicrobial cultures and previous positive blood culture in the same admission had lower odds of being rated preventable, compared with events without those attributes. Of 636 potentially preventable non-commensal HOB events, 47% were endovascular in origin, followed by gastrointestinal, respiratory and urinary sources; approximately 40% of those events would not be captured through existing healthcare-associated infection surveillance., Discussion: Factors identified as associated with higher or lower preventability should be used to guide inclusion, exclusion and risk adjustment for an HOB-related quality metric., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Childhood obesity is a complex public health challenge with profound implications for both physical and psychological well-being. A significant portion of the global population struggles with obesity. Sedentary lifestyles, increased consumption of ultra-processed foods, and socioeconomic disparities are major contributors. The COVID-19 pandemic has further exacerbated these issues, leading to a surge in obesity rates among children. The consequences of childhood obesity extend beyond immediate health issues like type 2 diabetes and cardiovascular diseases; obese children are at higher risk for psychological problems such as depression, anxiety, and low self-esteem, which can persist into adulthood. These health challenges also impose substantial economic burdens due to increased healthcare costs and reduced productivity. This paper synthesizes findings from various articles to provide an overview of the causes, consequences, and preventive strategies related to childhood obesity. It highlights the varied nature of obesity, including genetic, environmental, and lifestyle factors, and discusses the profound impact on physical health, socioemotional skills, and mental health. Additionally, it examines the global challenge of childhood obesity, particularly in developing nations, and emphasizes the importance of preventive measures, family and parental behaviors, and effective policy interventions., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Goel et al.)

Objective: Describe characteristics of preterm infants exposed to inhaled nitric oxide (iNO) in Kaiser Permanente Southern California., Study Design: Case review of preterm infants <34-weeks exposed to iNO during 2010-2020 including respiratory and echocardiographic status, NICU course, and 12-month follow-up., Results: 270 infants, 2.63% of births<34 weeks, (median, range: 26.1, 22 5/7 -33 6/7 weeks gestation) were exposed to iNO. Median FiO 2 at iNO initiation was 1.0 (IQR 0.94-1.0). Pulmonary hypertension (PH) was not associated with risk-adjusted 2 h oxygenation response or improved survival. Mortality to NICU discharge was 37.4%. Median cost of iNO was $7,695/patient. Discharged survivors experienced frequent rehospitalization (34.9%), use of supplemental oxygen, sildenafil, diuretics, bronchodilators, and steroids. Four infants had persistent PH. Five infants died after NICU discharge., Conclusions: Preterm infants receiving iNO have high mortality and 1st year morbidity. As currently used, iNO may be an indicator of respiratory disease severity rather than mediator of improved outcomes., (© 2024. The Author(s).)

The influence of boundary layer flow of heat transfer analysis on hybrid nanofluid across an extended cylinder is the main focus of the current research. In addition, the impressions of magnetohydrodynamic, porous medium and thermal radiation are part of this investigation. Arrogate similarity variables are employed to transform the governing modelled partial differential equations into a couple of highly nonlinear ordinary differential equations. A numerical approach based on the BVP Midrich scheme in MAPLE solver is employed for solution of the set of resulting ordinary differential equations and obtained results are compared with existing literature. The effect of active important physical parameters like Magnetic Field, Porosity parameter, Eckert number, Prandtl number and thermal radiation parameters on dimensionless velocity and energy fields are employed via graphs and tables. The velocity profile decreased by about 65% when the magnetic field parameter values increases from 0.5 to 1.5. On the other hand increased by 70% on energy profile. The energy profile enhanced by about 62% when the Radiation parameter values increases from 1.0 < Rd < 3.0. The current model may be applicable in real life practical implications of employing Engine oil-SWCNTs-MWCNTs-TiO 2 nanofluids on cylinders encompass enhanced heat transfer efficiency, and extended component lifespan, energy savings, and environmental benefits. This kind of theoretical analysis may be used in daily life applications, such as engineering and automobile industries., (© 2024. The Author(s).)

Background: Residents of nursing homes remain an epidemiologically important population for COVID-19 prevention efforts, including vaccination. We aim to understand effectiveness of bivalent vaccination for preventing SARS-CoV-2 infections in this population., Methods: We used a retrospective cohort of nursing home residents from November 1, 2022, through March 31, 2023, to identify new SARS-CoV-2 infections. A Cox proportional hazards model was used to estimate hazard ratios comparing residents with a bivalent vaccination compared with residents not up to date with vaccination recommendations. Vaccine effectiveness was estimated as (1 - Hazard Ratio) * 100., Results: Among 6,916 residents residing in 76 nursing homes included in our cohort, 3,211 (46%) received a bivalent vaccine 7 or more days prior to censoring. Adjusted vaccine effectiveness against laboratory confirmed SARS-CoV-2 infection comparing receipt of a bivalent vaccine versus not up to date vaccine status was 29% (95% Confidence interval 18% to 39%). Vaccine effectiveness for receipt of a bivalent vaccine against residents who were unvaccinated or vaccinated more than a year prior was 32% (95% CI: 20% to 42%,) and was 25% compared with residents who were vaccinated with a monovalent vaccine in the past 61-365 days (95% CI:10% to 37%)., Conclusions: Bivalent COVID-19 vaccines provided additional protection against SARS-CoV-2 infections in nursing home residents during our study time-period, compared to both no vaccination or vaccination more than a year ago and monovalent vaccination 60 - 365 days prior. Ensuring nursing home residents stay up to date with vaccine recommendations remains a critical tool for COVID-19 prevention efforts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Human blood vessel walls show concentric layers, with the outermost tunica adventitia harboring mesenchymal progenitor cells. These progenitor cells maintain vessel homeostasis and provide a robust cell source for cell-based therapies. However, human adventitial stem cell niche has not been studied in detail. Here, using spatial and single-cell transcriptomics, we characterized the phenotype, potential, and microanatomic distribution of human perivascular progenitors. Initially, spatial transcriptomics identified heterogeneity between perivascular layers of arteries and veins and delineated the tunica adventitia into inner and outer layers. From this spatial atlas, we inferred a hierarchy of mesenchymal progenitors dictated by a more primitive cell with a high surface expression of CD201 (PROCR). When isolated from humans and mice, CD201 Low expression typified a mesodermal committed subset with higher osteogenesis and less proliferation than CD201 High cells, with a downstream effect on canonical Wnt signaling through DACT2. CD201 Low cells also displayed high translational potential for bone tissue generation., Competing Interests: Declaration of interests A.W.J. declared scientific advisory board for Novadip LLC, consultant for Lifesprout LLC and Novadip LLC, and Editorial Board of Stem Cells, Bone Research, and American Journal of Pathology. K.B. declared consultant for Dilon Technologies. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy ( NCT05915741 ). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high degree of predictability. In patients with persistent symptoms (non-responders), predictability of the neural data remained consistently high. On the other hand, in patients who improved symptomatically (responders), predictability of the neural data was significantly diminished. This neural feature accurately classified clinical status even in patients with limited duration recordings, indicating generalizability that could facilitate therapeutic decision-making., (© 2024. The Author(s).)

Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy or "broken heart syndrome," is a rare and reversible condition characterized by transient left ventricular dysfunction. It is typically triggered by acute emotional or physical stressors. Here, we present a unique case of TCM occurring in a 77-year-old woman following cardioversion for persistent and symptomatic atrial fibrillation. The patient underwent uncomplicated cardioversion with recent imaging showing intact global systolic function. She presented four days post-procedure for chest pain, shortness of breath, and peripheral edema. A repeat echocardiogram showed a marked decrease in cardiac function evidenced by an ejection fraction of 20-25%. The patient was readmitted and managed with IV diuretics. Symptoms resolved within three days and the patient showed improved cardiac function on imaging prior to discharge., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Clydesdale et al.)

The proteasome controls levels of most cellular proteins, and its activity is regulated under stress, quiescence, and inflammation. However, factors determining the proteasomal degradation rate remain poorly understood. Proteasome substrates are conjugated with small proteins (tags) like ubiquitin and Fat10 to target them to the proteasome. It is unclear if the structural plasticity of proteasome-targeting tags can influence substrate degradation. Fat10 is upregulated during inflammation, and its substrates undergo rapid proteasomal degradation. We report that the degradation rate of Fat10 substrates critically depends on the structural plasticity of Fat10. While the ubiquitin tag is recycled at the proteasome, Fat10 is degraded with the substrate. Our results suggest significantly lower thermodynamic stability and faster mechanical unfolding in Fat10 compared to ubiquitin. Long-range salt bridges are absent in the Fat10 structure, creating a plastic protein with partially unstructured regions suitable for proteasome engagement. Fat10 plasticity destabilizes substrates significantly and creates partially unstructured regions in the substrate to enhance degradation. NMR-relaxation-derived order parameters and temperature dependence of chemical shifts identify the Fat10-induced partially unstructured regions in the substrate, which correlated excellently to Fat10-substrate contacts, suggesting that the tag-substrate collision destabilizes the substrate. These results highlight a strong dependence of proteasomal degradation on the structural plasticity and thermodynamic properties of the proteasome-targeting tags., Competing Interests: HN, AR, PD, SR, RD No competing interests declared, (© 2024, Negi et al.)

Aging is a major driver of diseases in humans. Identifying features associated with aging is essential for designing robust intervention strategies and discovering novel biomarkers of aging. Extensive studies at both the molecular and organ/whole-body physiological scales have helped determined features associated with aging. However, the lack of meso-scale studies, particularly at the tissue level, limits the ability to translate findings made at molecular scale to impaired tissue functions associated with aging. In this work, we established a tissue image analysis workflow - quantitative micro-anatomical phenotyping (qMAP) - that leverages deep learning and machine vision to fully label tissue and cellular compartments in tissue sections. The fully mapped tissue images address the challenges of finding an interpretable feature set to quantitatively profile age-related microanatomic changes. We optimized qMAP for skin tissues and applied it to a cohort of 99 donors aged 14 to 92. We extracted 914 microanatomic features and found that a broad spectrum of these features, represented by 10 cores processes, are strongly associated with aging. Our analysis shows that microanatomical features of the skin can predict aging with a mean absolute error (MAE) of 7.7 years, comparable to state-of-the-art epigenetic clocks. Our study demonstrates that tissue-level architectural changes are strongly associated with aging and represent a novel category of aging biomarkers that complement molecular markers. Our results highlight the complex and underexplored multi-scale relationship between molecular and tissue microanatomic scales., Competing Interests: Conflict of Interest The authors declare no financial/commercial conflicts of interest.

The domain of object detection was revolutionized with the introduction of Convolutional Neural Networks (CNNs) in the field of computer vision. This article aims to explore the architectural intricacies, methodological differences, and performance characteristics of three CNN-based object detection algorithms, namely Faster Region-Based Convolutional Network (R-CNN), You Only Look Once v3 (YOLO), and Single Shot MultiBox Detector (SSD) in the specific domain application of vehicle detection. The findings of this study indicate that the SSD object detection algorithm outperforms the other approaches in terms of both performance and processing speeds. The Faster R-CNN approach detected objects in images with an average speed of 5.1 s, achieving a mean average precision of 0.76 and an average loss of 0.467. YOLO v3 detected objects with an average speed of 1.16 s, achieving a mean average precision of 0.81 with an average loss of 1.183. In contrast, SSD detected objects with an average speed of 0.5 s, exhibiting the highest mean average precision of 0.92 despite having a higher average loss of 2.625. Notably, all three object detectors achieved an accuracy exceeding 99%.

What Is This Summary About?: This is a summary of two studies that looked at the safety and effectiveness of a potential new treatment, N-803 (Anktiva), in combination with a standard treatment bacillus Calmette-Guerin (BCG) for people with non-muscle invasive bladder cancer (NMIBC) .One study was a Phase 1b study that tested increasing doses of N-803 in combination with the same dose of BCG in people with NMIBC who had never received BCG previously (BCG-naive). The other study is a Phase 2/3 study of N-803 and BCG in people with NMIBC whose cancer wasn't eliminated by BCG alone (BCGunresponsive)., What Happened in the Studies?: In the Phase 1b study, the nine participants were split into three groups of 3 participants who received a dose of 100, 200, or 400 μg N-803 along with a standard 50 mg dose of BCG. In the Phase 2/3 study, one group (cohort A) of participants with carcinoma in situ (CIS) disease and another group (cohort B) with papillary disease were treated with 400 μg N-803 plus 50 mg BCG. There was also a cohort C that received only 400 μg N-803. Treatments were delivered directly into the bladder once a week for 6 weeks in a row., What Were the Key Takeaways?: N-803 plus BCG eliminated NMIBC in all nine BCG-naive participants and the effects were long-lasting, with participants remaining NMIBC-free for a range of 8.3 to 9.2 years.As reported in 2022, cancer was eliminated in 58 of 82 (71%) participants with BCG-unresponsive CIS disease and the effect was also long-lasting. Importantly, approximately 90% of the successfully treated participants avoided surgical removal of the bladder. In cohort B participants with papillary disease, 40 of 72 (55.4%) were cancer-free 12 months after treatment. N-803 used alone was only effective in 2 of 10 participants. In both studies, the combination of N-803 and BCG was found to be associated with very few adverse events.Based on results from the Phase 2/3 study, the U.S. Food and Drug Association (FDA) approved the use of N-803 plus BCG for the treatment of BCG-unresponsive bladder CIS with or without Ta/T1 papillary disease. Clinical Trial Registration: NCT02138734 (Phase 1b study), NCT03022825 (Phase 2/3 study).

Background: Patient engagement technologies (PETs) guide patients through the perioperative period. We aimed to investigate the levels of patient engagement with PETs through the peri-operative period and its impact on clinical outcomes., Methods: Retrospective cohort study of patients undergoing elective colorectal surgery from 2018 to 2022. Outcomes were length of stay, readmissions, and complications within 30 days of index hospitalization., Results: 359 (89.1%) patients activated the PET. Patients completed a median of 7 surveys, 2 in-hospital health-checks, and 1 post-discharge health-check. Median LOS was 3 days, 57 (14.1%) patients were readmitted, and 56 (13.9%) had a complication. Patients who completed no surveys had longer LOS than those who completed 2 or more. Patients who were readmitted and had post-operative complications completed significantly fewer surveys and post-discharge health-checks. Completion of surveys in more phases was associated with shorter LOS and lower readmission rates. Completion of more post-discharge health-checks was associated with lower complication rate., Conclusions: The use of PETs improves patient outcomes and experiences in the perioperative period. Patients who engage more frequently with PETs have shorter LOS with lower readmission and post-operative complication rates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Study Aims: Endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) has been well utilized in treating malignant gastric outlet obstructions (GOO) given its efficacy and lower risk profile compared to surgery. However, its efficacy and potential for use in patients with benign GOO who are poor surgical candidates is not well documented. The aim of this study was to examine the role of EUS-GJ in treatment of benign GOO in select patients., Patients and Methods: This is a single-center, open-label, retrospective descriptive study that included all consecutive patients undergoing EUS-GJ to treat benign causes of GOO. Direct antegrade and direct retrograde methods were utilized., Results: A total of 18 patients were included, 38.9% female with an average age of 63.3 years. Extrinsic GOO was present in (10 of 18) 55.5% of patients and intrinsic etiology was present in (8 of 18) 45.5% of patients. Technical success was achieved in 100% (18 of 18) patients and clinical success was achieved in 94% (17 of 18) patients. In total, 13 patients had follow-up endoscopy, 2 patients were treated relatively recently in time, 1 patient was lost to follow-up, and 2 patients died of other chronic illnesses. Stents remained in place for a median of 286 days (range 88-1444 days). In patients whose stents were removed, 75% (3 of 4) had extrinsic etiologies of GOO., Conclusions: This study reports a favorable long-term patency with excellent technical and clinical success of EUS-GJ in patients with benign GOO. Despite the limitations of sample size and retrospective nature, it adds to the extremely limited literature of EUS-GJ in management of patients with benign GOO., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: To study the effect of bempedoic acid on markers of inflammation and lipoprotein (a) to help determine if the drug would be useful to treat patients with elevated cardiovascular risks and residual cardiovascular risk despite optimal low-density lipoprotein cholesterol (LDL-C) levels., Recent Findings: Bempedoic acid is found to cause significant reduction in LDL-C and high-sensitivity C-reactive protein (hs-CRP) in various randomized clinical trials. Multiple meta-analyses have also found that bempedoic acid therapy leads to reduction in non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC) and apolipoprotein B (ApoB) levels. However, it has minimal effect on lipoprotein (a) (Lp(a)) level., Summary: Bempedoic acid is a new lipid-lowering agent that inhibits enzyme ATP-citrate lyase in the cholesterol biosynthesis pathway. Major risk of cardiovascular events and its associated morbidity and mortality are proportional to LDL-C and inflammatory markers levels. It was found that bempedoic acid significantly lowers LDL-C, hs-CRP and other inflammatory markers levels. This drug could potentially be used in patients with elevated cardiovascular risk, in patients with residual cardiovascular risk despite attaining LDL-C goal and in statin intolerant patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Coronary heart disease and cancer are the most common causes of mortality across the globe. It has been a dilemma for the surgical team to decide which surgical procedure should be done first when a patient needs surgery for both. This is a single-center retrospective observational study. Six patients who underwent simultaneous coronary artery bypass graft (CABG) and oncological surgeries between January 2018 and July 2021 were included in the study. One patient underwent lung bilobectomy via the same sternotomy incision; one underwent surgery for breast cancer, stomach cancer, and colon cancer; and one patient each of buccal mucosa carcinoma and tongue carcinoma. The median age was 65 years (59-70). Median blood loss was 550 ml (400-800). The median intensive care unit (ICU) stay was 60 h (46-130) and hospital stay was 7.5 days (6-14). The median follow-up of the present study was 31.5 months (6-38). One patient with lung carcinoma developed recurrence after 6 months and the patient is in remission after a follow-up of 32 months. Simultaneous CABG and oncological resection can be performed effectively and safely by an experienced team of cardiothoracic surgeons, surgical oncologists, and anesthetists after good patient selection., Competing Interests: Competing interestsThe authors declare no competing interests., (© Indian Association of Cardiovascular-Thoracic Surgeons 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Clavulanic acid (CLAV) is a component of Augmentin® that preserves antibiotic efficacy by inhibiting β-lactamase activity. It also enhances cellular glutamate uptake and is a potential CNS therapeutic. Because increased glutamate transmission in brain reward circuits facilitates methamphetamine (METH) locomotor activation and sensitization, we tested the hypothesis that CLAV inhibits acute and sensitized locomotor responses to METH in mice and investigated effects of CLAV on METH-induced changes in glutaminase, the major glutamate-producing enzyme in the brain. Acute METH (3 mg/kg) produced hyperlocomotion that was reduced by CLAV (20 mg/kg but not 10 mg/kg). Mice injected with METH (3 mg/kg) every other day for 9 d and then challenged with METH 27 d later displayed locomotor sensitization. CLAV (10 mg/kg), when injected 15 min before each METH injection during the 9-d exposure interval, blocked locomotor sensitization induced by METH challenge. In METH-sensitized mice, mRNA levels of both isoforms of glutaminase (GLS and GLS2) were altered in the nucleus accumbens compared to mice exposed to a single injection of METH (i.e., GLS decreased and GLS2 increased). CLAV normalized the METH-induced GLS deficit but not the increase in GLS2. In summary, CLAV reduced acute and sensitized locomotor responses to METH and normalized the METH-induced reduction of GLS gene expression in the NAC. Given that glutaminases belong to the β-lactamase superfamily and CLAV is a β-lactamase inhibitor, our data point toward studying glutaminase as a therapeutic target of CLAV., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Appendectomy ranks among the most common surgical procedures. Laparoscopic appendectomy has become increasingly popular among certain surgeons. Even laparoscopic appendectomy is considered the gold standard; many surgical subspecialties have adopted robotic surgery in the past 10 years. The robotic system is recognized for enhancing stability, visualization, precision, and spatial flexibility. Surgeons can operate with enhanced dexterity, reduced tremors, three-dimensional visualization, up to 10 times magnification, and control over four arms thanks to improved ergonomics that allow them to sit at a customizable console. The purpose of this study is to evaluate and compare the overall effects, such as intraoperative time, postoperative recovery, feasibility for surgeons, and cost-effectiveness, of robotic-assisted appendectomy and laparoscopic appendectomy through the available literature. It was found that both robotic and laparoscopic surgeries work well for appendectomy, but in some studies, it was found that robotic surgery comes with the perks of shorter hospital stays and quicker recovery, even though it is more expensive, and in some studies, no differences were observed in patient recovery postoperatively. Laparoscopic surgery is still a highly effective and commonly used method, with proven advantages over open appendectomy, despite taking longer for the procedure. We need more studies to fully understand the advantages and disadvantages of robotic surgery, especially when it comes to cost-effectiveness and wider health outcomes., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Reddy et al.)

Rare-earth element Gd doped CoSi, Co1-xGd x Si ( x = 0.01), is investigated using x-ray diffraction and magnetization. It crystallizes in B20 cubic structure with lattice parameter of a = 4.4429 Å. The alloy exhibits two antiferromagnetic transitions AFM-I at 38.44 K and AFM-II at 21.87 K followed by an upturn of magnetization belowTut= 9.79 K as illustrated through the temperature-magnetic field T-H phase diagram. AFM-I state is incommensurate. AFM-II state is weakly correlated as inferred from field-induced transition to AFM-I state. Further, AFM-I state is reported to transform to ferromagnetic state in high magnetic fields. The present study stimulates an approach to derive novel and exotic magnetic materials by substituting rare-earth in transition metal monosilicides., (© 2024 IOP Publishing Ltd.)

Background: Pathogenic concepts of right ventricular (RV) failure in pulmonary arterial hypertension focus on a critical loss of microvasculature. However, the methods underpinning prior studies did not take into account the 3-dimensional (3D) aspects of cardiac tissue, making accurate quantification difficult. We applied deep-tissue imaging to the pressure-overloaded RV to uncover the 3D properties of the microvascular network and determine whether deficient microvascular adaptation contributes to RV failure., Methods: Heart sections measuring 250-µm-thick were obtained from mice after pulmonary artery banding (PAB) or debanding PAB surgery and properties of the RV microvascular network were assessed using 3D imaging and quantification. Human heart tissues harvested at the time of transplantation from pulmonary arterial hypertension cases were compared with tissues from control cases with normal RV function., Results: Longitudinal 3D assessment of PAB mouse hearts uncovered complex microvascular remodeling characterized by tortuous, shorter, thicker, highly branched vessels, and overall preserved microvascular density. This remodeling process was reversible in debanding PAB mice in which the RV function recovers over time. The remodeled microvasculature tightly wrapped around the hypertrophied cardiomyocytes to maintain a stable contact surface to cardiomyocytes as an adaptation to RV pressure overload, even in end-stage RV failure. However, microvasculature-cardiomyocyte contact was impaired in areas with interstitial fibrosis where cardiomyocytes displayed signs of hypoxia. Similar to PAB animals, microvascular density in the RV was preserved in patients with end-stage pulmonary arterial hypertension, and microvascular architectural changes appeared to vary by etiology, with patients with pulmonary veno-occlusive disease displaying a lack of microvascular complexity with uniformly short segments., Conclusions: 3D deep tissue imaging of the failing RV in PAB mice, pulmonary hypertension rats, and patients with pulmonary arterial hypertension reveals complex microvascular changes to preserve the microvascular density and maintain a stable microvascular-cardiomyocyte contact. Our studies provide a novel framework to understand microvascular adaptation in the pressure-overloaded RV that focuses on cell-cell interaction and goes beyond the concept of capillary rarefaction., Competing Interests: Disclosures None.

We have demonstrated a Pd(0)-catalyzed Heck/C(sp 3 )-H activation cascade for the synthesis of spirocyclopropyl oxindoles in high yields from easily accessible ortho -bromoacrylamides. The formation of spirocyclopropyl oxindole is guided by an unconventional four-membered palladacycle through C(sp 3 )-H activation. The reaction exhibits a wide range of substrate scope and operates efficiently with a mere 0.5 mol % of Pd-catalyst. In addition, the use of microwave conditions facilitates rapid completion of the reaction. Furthermore, this spirocyclopropanation strategy can be coupled with [3 + 2] cycloaddition to produce spiropyrrolidine oxindoles, offering a valuable approach for the preparation of alkaloids such as (±)-horsfiline and (±)-coerulescine.

Parotid gland is the largest salivary gland of the body. Pleomorphic adenomas are the most prevalent benign parotid gland tumors. They can eventually grow to a size where they weigh several kilograms if not timely addressed. The 'pleomorphic' characteristics are attributed to the origin of the tumor from the connective tissue and epithelium. Pleomorphic adenomas often arise from the superficial lobe, further extending into the parapharyngeal space and gland's other deeper tissues. Common incidence is noted in females between 30 and 50 years. Tumors typically present as asymptomatic swelling and progress slowly. The cornerstone of treatment is surgical removal of the tumor mass, with great care being given to protect the facial nerve. Most of these tumors are observed with the involvement of the superficial lobe; only a few are observed involving the deep lobe. This case report presents an intriguing case of a pleomorphic adenoma of superficial and deep parotid gland in a 65-year-old male. The left side of the patient's face had a steadily increasing, asymptomatic swelling on admission. Magnetic resonance imaging of the neck revealed a pleomorphic adenoma of the superficial and deep parotid gland. The patient underwent surgical excision of the parotid gland, which was uneventful., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sudabattula et al.)

Importance: Urinary tract infection (UTI) is the second most common infection leading to hospitalization and is often associated with gram-negative multidrug-resistant organisms (MDROs). Clinicians overuse extended-spectrum antibiotics although most patients are at low risk for MDRO infection. Safe strategies to limit overuse of empiric antibiotics are needed., Objective: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO risk estimates could reduce use of empiric extended-spectrum antibiotics for treatment of UTI., Design, Setting, and Participants: Cluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time and risk-based CPOE prompts; 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in noncritically ill adults (≥18 years) hospitalized with UTI with an 18-month baseline (April 1, 2017-September 30, 2018) and 15-month intervention period (April 1, 2019-June 30, 2020)., Interventions: CPOE prompts recommending empiric standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics who have low estimated absolute risk (<10%) of MDRO UTI, coupled with feedback and education., Main Outcomes and Measures: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy. Safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes were assessed using generalized linear mixed-effect models to assess differences between the baseline and intervention periods., Results: Among 127 403 adult patients (71 991 baseline and 55 412 intervention period) admitted with UTI in 59 hospitals, the mean (SD) age was 69.4 (17.9) years, 30.5% were male, and the median Elixhauser Comorbidity Index count was 4 (IQR, 2-5). Compared with routine stewardship, the group using CPOE prompts had a 17.4% (95% CI, 11.2%-23.2%) reduction in empiric extended-spectrum days of therapy (rate ratio, 0.83 [95% CI, 0.77-0.89]; P < .001). The safety outcomes of mean days to ICU transfer (6.6 vs 7.0 days) and hospital length of stay (6.3 vs 6.5 days) did not differ significantly between the routine and intervention groups, respectively., Conclusions and Relevance: Compared with routine stewardship, CPOE prompts providing real-time recommendations for standard-spectrum antibiotics for patients with low MDRO risk coupled with feedback and education significantly reduced empiric extended-spectrum antibiotic use among noncritically ill adults admitted with UTI without changing hospital length of stay or days to ICU transfers., Trial Registration: ClinicalTrials.gov Identifier: NCT03697096.

Importance: Pneumonia is the most common infection requiring hospitalization and is a major reason for overuse of extended-spectrum antibiotics. Despite low risk of multidrug-resistant organism (MDRO) infection, clinical uncertainty often drives initial antibiotic selection. Strategies to limit empiric antibiotic overuse for patients with pneumonia are needed., Objective: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO infection risk estimates could reduce empiric extended-spectrum antibiotics for non-critically ill patients admitted with pneumonia., Design, Setting, and Participants: Cluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time MDRO risk-based CPOE prompts; n = 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in non-critically ill adults (≥18 years) hospitalized with pneumonia. There was an 18-month baseline period from April 1, 2017, to September 30, 2018, and a 15-month intervention period from April 1, 2019, to June 30, 2020., Intervention: CPOE prompts recommending standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics during the empiric period who have low estimated absolute risk (<10%) of MDRO pneumonia, coupled with feedback and education., Main Outcomes and Measures: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy and safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes compared differences between baseline and intervention periods across strategies., Results: Among 59 hospitals with 96 451 (51 671 in the baseline period and 44 780 in the intervention period) adult patients admitted with pneumonia, the mean (SD) age of patients was 68.1 (17.0) years, 48.1% were men, and the median (IQR) Elixhauser comorbidity count was 4 (2-6). Compared with routine stewardship, the group using CPOE prompts had a 28.4% reduction in empiric extended-spectrum days of therapy (rate ratio, 0.72 [95% CI, 0.66-0.78]; P < .001). Safety outcomes of mean days to ICU transfer (6.5 vs 7.1 days) and hospital length of stay (6.8 vs 7.1 days) did not differ significantly between the routine and CPOE intervention groups., Conclusions and Relevance: Empiric extended-spectrum antibiotic use was significantly lower among adults admitted with pneumonia to non-ICU settings in hospitals using education, feedback, and CPOE prompts recommending standard-spectrum antibiotics for patients at low risk of MDRO infection, compared with routine stewardship practices. Hospital length of stay and days to ICU transfer were unchanged., Trial Registration: ClinicalTrials.gov Identifier: NCT03697070.

Free (unbound) drug concentration at the site of action is the key determinant of biologic activity since only unbound drugs can exert pharmacological and toxicological effects. Unbound drug concentration in tumors for solid cancers is needed to understand/explain/predict pharmacokinetics, pharmacodynamics, and efficacy relations. Fraction unbound ( f u ) in tumors is usually determined across several xenografted tumors derived from various cell lines in the drug discovery stage, which is time consuming and a resource burden. In this study, we determined the f u values for a set of diverse compounds (comprising acid, base, neutral, zwitterion, and covalent drugs) across five different xenografted tumors and five commercially available mouse tissues to explore the correlation of f u between tumors and the possibility of surrogate tissue(s) for tumor f u (f u,tumor ) determination. The crosstumor comparison showed that f u,tumor values across tumors are largely comparable, and systematic tissue versus tumor comparison demonstrated that only lung tissue had comparable f u to all five tumors ( f u values within twofold change for >80% compounds in both comparisons). These results indicated that mouse lung tissue can be used as a surrogate matrix for a f u,tumor assay. This study will increase efficiency in f u,tumor assessment and reduce animal use (adapting the replace, reduce, and refine principle) in drug discovery. SIGNIFICANCE STATEMENT: The free drug concept is a well accepted principle in drug discovery research. Currently, tumor fraction unbound (f u,tumor ) is determined in several tumors derived from different cell lines to estimate free drug concentrations of a compound. The results from this study indicated that f u,tumor across xenografted tumors is comparable, and f u,tumor can be estimated using a surrogate tissue, mouse lung. The results will increase efficiency in f u,tumor assessment and reduce animal use in drug discovery., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

Diagnostic markers are desperately needed for the early detection of pancreatic ductal adenocarcinoma (PDA). We describe sets of markers expressed in temporal order in mouse models during pancreatitis, PDA initiation and progression. Cell type specificity and the differential expression of PDA markers were identified by screening single cell (sc) RNAseq from tumor samples of a mouse model for PDA (KIC) at early and late stages of PDA progression compared to that of a normal pancreas. Candidate genes were identified from three sources: (1) an unsupervised screening of the genes preferentially expressed in mouse PDA tumors; (2) signaling pathways that drive PDA, including the Ras pathway, calcium signaling, and known cancer genes, or genes encoding proteins that were identified by differential mass spectrometry (MS) of mouse tumors and conditioned media from human cancer cell lines; and (3) genes whose expression is associated with poor or better prognoses (PAAD, oncolnc.org). The developmental progression of PDA was detected in the temporal order of gene expression in the cancer cells of the KIC mice. The earliest diagnostic markers were expressed in epithelial cancer cells in early-stage, but not late-stage, PDA tumors. Other early markers were expressed in the epithelium of both early- and late-state PDA tumors. Markers that were expressed somewhat later were first elevated in the epithelial cancer cells of the late-stage tumors, then in both epithelial and mesenchymal cells, or only in mesenchymal cells. Stromal markers were differentially expressed in early- and/or late-stage PDA neoplasia in fibroblast and hematopoietic cells (lymphocytes and/or macrophages) or broadly expressed in cancer and many stromal cell types. Pancreatitis is a risk factor for PDA in humans. Mouse models of pancreatitis, including caerulein treatment and the acinar-specific homozygous deletion of differentiation transcription factors (dTFs), were screened for the early expression of all PDA markers identified in the KIC neoplasia. Prognostic markers associated with a more rapid decline were identified and showed differential and cell-type-specific expression in PDA, predominately in late-stage epithelial and/or mesenchymal cancer cells. Select markers were validated by immunohistochemistry in mouse and human samples of a normal pancreas and those with early- and late-stage PDA. In total, we present 2165 individual diagnostic and prognostic markers for disease progression to be tested in humans from pancreatitis to late-stage PDA.

Acute pancreatitis is a dynamic inflammatory condition of the pancreas with a spectrum ranging from mild to severe. Early and accurate assessment of disease severity is crucial for guiding clinical management and improving patient outcomes. This comprehensive review explores the role of radiological and biochemical parameters in assessing the severity of acute pancreatitis. Radiological imaging modalities, including computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US), play a pivotal role in identifying key features, such as pancreatic necrosis and peripancreatic fluid collections, indicative of severe disease. Additionally, serum markers such as amylase, lipase, and C-reactive protein (CRP) provide valuable prognostic information and aid in risk stratification. Integrating radiological and biochemical parameters allows for a multidimensional evaluation of disease severity, enabling clinicians to make informed decisions regarding patient management. Early identification of severe cases facilitates timely interventions, including intensive care monitoring, nutritional support, and potential surgical interventions. Despite significant advancements in the field, there remain areas for further research, including the validation of emerging imaging techniques and biomarkers and the exploration of personalized management approaches. Addressing these research gaps can enhance our understanding of acute pancreatitis and ultimately improve patient care and outcomes., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Bikkumalla et al.)

Background: Caregivers of children with chronic kidney disease (CKD) in low resource settings must provide complex medical care at home while being burdened by treatment costs often paid out-of-pocket. We hypothesize that caregiver burden in our low resource setting is greater than reported from high income countries and is associated with frequent catastrophic healthcare expenditure (CHE)., Methods: We conducted a mixed-methods study of primary caregivers of children with advanced CKD (stage 3b-5) in our private-sector referral hospital in a low resource setting. We assessed caregiver burden using the Pediatric Renal Caregiver Burden Scale (PRCBS) and measured financial burden by calculating the proportion of caregivers who experienced CHE (monthly out-of-pocket healthcare expenditure exceeding 10% of total household monthly expenditure). We performed a qualitative reflexive thematic analysis of caregiver interviews to explore sources of burden., Results: Of the 45 caregivers included, 35 (78%) had children on maintenance dialysis (25 PD, 10 HD). Mean caregiver burden score was 141 (± 17), greater than previously reported. On comparative analysis, PRCBS scores were higher among caregivers of children with kidney failure (p = 0.005), recent hospitalization (p = 0.03), non-earning caregivers (p = 0.02), caring for > 2 dependents (p = 0.009), and with high medical expenditure (p = 0.006). CHE occurred in 43 (96%) caregivers of whom 37 (82%) paid out-of-pocket. The main themes derived relating to caregiver burden were severe financial burden, mental stress and isolation, and perpetual burden of concern., Conclusion: Parents of children with CKD experienced severe caregiver burden with frequent CHE and relentless financial stress indicating an imminent need for social support interventions., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Cardiorenal syndrome (CRS) due to right ventricular (RV) failure is a disease entity emerging as a key indicator of morbidity and mortality. The multifactorial aspects of CRS and the left-right ventricular interdependence complicate the link between RV failure and renal function. RV failure has a direct pathophysiological link to renal dysfunction by leading to systemic venous congestion in certain circumstances and low cardiac output in other situations, both leading to impaired renal perfusion. Indeed, renal dysfunction is known to be an independent predictor of mortality in patients with pulmonary arterial hypertension (PAH) and RV failure. Thus, it is important to further understand the interaction between the RV and renal function. RV adaptation is critical to long-term survival in patients with PAH. The RV is also known for its remarkable capacity to recover once the aggravating factor is addressed or mitigated. However, less is known about the renal potential for recovery following the resolution of chronic RV failure. In this review, we provide an overview of the intricate relationship between RV dysfunction and the subsequent development of CRS, with a particular emphasis on PAH. Additionally, we summarize potential RV-targeted therapies and their potential beneficial impact on renal function., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cerebral mycotic aneurysms (CMA) are a rare consequence of infective endocarditis (IE). We report a case of a 75-year-old left-handed male with comorbidities who was admitted to our facility with left-sided weakness, dysarthria, and left-sided facial droop. Initial computed tomography of the head without contrast and angiography of the head showed acute hemorrhage in the paramedian right frontal lobe with extension into the right lateral ventricle, occlusion of the left intracranial internal carotid artery, and an associated 0.3 cm aneurysm involving the distal right anterior cerebral artery. C-reactive protein and erythrocyte sedimentation rate were elevated but blood cultures showed no growth for more than five days. The patient underwent a two-vessel cerebral angiogram, primary coil embolization of the aneurysm, and selective catheterization of the left common carotid artery, right internal carotid artery, and right anterior cerebral artery. Transesophageal echocardiography showed an echogenic, highly mobile structure attached to the aortic valve suggestive of vegetation. The patient was subsequently started on a vancomycin regimen and stably discharged for further outpatient follow-up. This case highlights an uncommon presentation of CMA and the retroactive diagnosis of IE., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Khalafi et al.)

Purpose: Currently, 1 in 5 college students struggle with suicidal ideation while 7% to 44% engage in nonsuicidal self-injury. Illinois has one of the highest teenage and college student suicide rates in the United States. This pilot study assessed suicide ideation and self-harm behaviors at a public Illinois university. This is the first study to use 5 standardized psychological instruments to investigate these 2 crises in freshmen college students who are all required to reside in dormitories. The main hypothesis was to determine if the independent effects of freshmen students' depression, Five-Factor Model, and Reasons for Living affected the dependent variables, self-harm behaviors and suicide ideation. Methods: Forty first-year college dormitory students completed the Beck Depression Inventory-II, Scale of Suicidal Ideation, Five-Factor Model, Inventory of Statements About Self-Injury, and Reasons for Living Scale in person. Results: Participants were 18 to 19 years old, predominantly female (65%), and non-White (62%). Forty percent reported self-harm behaviors and 19% reported suicidal ideation. The top reasons for contemplated suicide attempts included the inability to solve problems (33%) and attention/revenge (28%). Students experienced high levels of anxiety (55%), self-consciousness (43%), and depression (18%). Depression was associated with suicide ideation (β   = 0.05, P  = .006), while neuroticism and openness were associated with self-harm behaviors ( aOR  = 3.36, P  = .02, aOR  = 0.48, P  = .047, respectively). Ninety-five percent reported "responsibility to family" as a Reason for Living. Conclusions: Preliminary evidence necessitates an examination of self-harm and suicide ideation among all freshmen, investigating both risk and protective factors. In the future, a prevention intervention should be implemented campus-wide (and eventually nationwide) for all first-year dormitory students to enhance their mental well-being., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objective: The 2014 US National Strategy for Combating Antibiotic-Resistant Bacteria (CARB) aimed to reduce inappropriate inpatient antibiotic use by 20% for monitored conditions, such as community-acquired pneumonia (CAP), by 2020. We evaluated annual trends in length of therapy (LOT) in adults hospitalized with uncomplicated CAP from 2013 through 2020., Methods: We conducted a retrospective cohort study among adults with a primary diagnosis of bacterial or unspecified pneumonia using International Classification of Diseases Ninth and Tenth Revision codes in MarketScan and the Centers for Medicare & Medicaid Services databases. We included patients with length of stay (LOS) of 2-10 days, discharged home with self-care, and not rehospitalized in the 3 days following discharge. We estimated inpatient LOT based on LOS from the PINC AI Healthcare Database. The total LOT was calculated by summing estimated inpatient LOT and actual postdischarge LOT. We examined trends from 2013 to 2020 in patients with total LOT >7 days, which was considered an indicator of likely excessive LOT., Results: There were 44,976 and 400,928 uncomplicated CAP hospitalizations among patients aged 18-64 years and ≥65 years, respectively. From 2013 to 2020, the proportion of patients with total LOT >7 days decreased by 25% (68% to 51%) among patients aged 18-64 years and by 27% (68%-50%) among patients aged ≥65 years., Conclusions: Although likely excessive LOT for uncomplicated CAP patients decreased since 2013, the proportion of patients treated with LOT >7 days still exceeded 50% in 2020. Antibiotic stewardship programs should continue to pursue interventions to reduce likely excessive LOT for common infections.