bluuebunny/crossref_metadata_2025_split huggingface dataset:
“It’s What We Can Do Right Now”: Professional Identity Formation Among Internal Medicine Residents During the COVID-19 Pandemic
Authors: Madrazo Lorenzo , Zhang Grace , Bishop Kristen A. , Appleton Andrew , Joneja Mala , Goldszmidt Mark 
Published: September 2023

Abstract

Purpose
The COVID-19 pandemic represents a consequential moment of disruption for medical training that has far-reaching implications for professional identity formation (PIF). To date, this has not been studied. As medical education grapples with a postpandemic era, it is essential to gain insight into how the pandemic has influenced PIF to better support its positive influences and mitigate its more detrimental effects. This study examined how PIF occurred during the COVID-19 pandemic to better adapt future medical training.

Method
Constructivist grounded theory guided the iterative data collection and analyses. The authors conducted semistructured group interviews with 24 Ontario internal medicine residents in postgraduate years (PGYs) 1 to 3 between November 2020 and July 2021. Participants were asked to reflect on their day-to-day clinical and learning experiences during the pandemic.

Results
Twenty-four internal medicine residents were interviewed (12 PGY-1 [50.0%], 9 PGY-2 [37.5%], and 3 PGY-3 [12.5%]). Participants described how navigating patient care and residency training through the pandemic consistently drew their attention to various system problems. How participants responded to these problems was shaped by an interplay among their personal values, their level of personal wellness or burnout, self-efficacy, institutional values, and the values of their supervisors and work community. As they were influenced by these factors, some were led toward acting on the problem(s) they identified, whereas others had a sense of resignation and deferred action. These interactions were evident in participants' experiences with communication, advocacy, and learning.

Conclusions
Residents' professional identities are continuously shaped by how they perceive, reconcile, and address various challenges. As residents navigate tensions between personally held values and apparent system values, individuals in supervisory positions should be mindful of their influence as role models who empower values and practices that are recognized by participants to be important aspects of physician identity.
Optimal Dosing of Levetiracetam for Seizure Prophylaxis in Critically Ill Patients: A Prospective Observational Study
Authors: Valdes Eduard , Fang Taolin , Boffa Michael , Frontera Jennifer A. 
Published: September 2023

OBJECTIVES:
Critically ill patients eliminate levetiracetam (LEV) more rapidly than healthy controls, yet low doses are commonly used for seizure prophylaxis in the ICU setting. We compared the rates of achievement of target serum levels and new onset seizure (clinical and/or electrographic) among patients who received low (500 mg bid) versus high (750–1,000 mg bid) dose LEV.

DESIGN:
Prospective, observational study.

SETTING:
Tertiary care, academic center.

PATIENTS:
We included patients who received prophylactic LEV following traumatic brain injury, intracerebral hemorrhage, spontaneous subarachnoid hemorrhage, or supratentorial neurosurgery between 2019 and 2021. Patients with a history of seizure, antiseizure medication use, or renal failure requiring dialysis were excluded.

INTERVENTIONS:
None.

Measurements:
LEV levels were obtained at steady state. The impact of low-dose versus high-dose LEV on the primary outcome of target LEV levels (12–46 μg/mL), and the secondary outcome of clinical and/or electrographic seizure, were assessed using multivariable logistic regression analyses adjusting for age, LEV loading dose, BMI, primary diagnosis and creatinine clearance (CrCl).

Main Results:
Of the 205 subjects included in analyses, n = 106 (52%) received LEV 500 mg bid (median 13 mg/kg/d), and n = 99 (48%) received LEV 750–1,000 mg bid (median 25 mg/kg/d). Overall, 111 of 205 patients (54%) achieved target levels: 48 (45%) from the low-dose group versus 63 (64%) from the high-dose group (odds ratio [OR] 2.1; 95% CI, 1.1–3.7; p = 0.009). In multivariable analyses, high-dose LEV predicted target levels (adjusted OR [aOR] 2.23; 95% CI, 1.16–4.27; p = 0.016), and was associated with lower seizure odds (aOR 0.32; 95% CI, 0.13–0.82; p = 0.018) after adjusting for age, loading dose, BMI, diagnosis, and CrCl.

CONCLUSIONS:
Underdosing of LEV was common, with only 54% of patients achieving target serum levels. Higher doses (750–1,000 mg bid) were more than twice as likely to lead to optimal drug levels and reduced the odds of seizure by 68% compared with low-dose regimens (500 mg bid).
Characterization of Polymicrobial and Antibiotic-Resistant Infectious Keratitis in a County Hospital Setting
Authors: Chan Lawrence , Lopez Jacqueline B. , Saifee Murtaza , Padmanabhan Sriranjani , Chan Matilda F. , Yung Madeline 
Published: September 2023

Purpose:
Infectious keratitis is a serious cause of visual impairment, particularly in low-income communities. This study examines the associations between social risk factors and polymicrobial keratitis, multidrug resistance, pathogen spectrum, and outcomes at a county hospital.

Methods:
We performed a retrospective study of Zuckerberg San Francisco General Hospital patients treated for infectious keratitis from 2010 to 2021. Multivariable regression was performed to analyze the relationships between social, medical, and psychiatric risk factors with polymicrobial growth, multidrug resistance, and clinical outcomes.

Results:
Of 174 patients with infectious keratitis, 44 (25%) had polymicrobial growth. Six patients (14%) with polymicrobial growth had multidrug-resistant organisms. Homeless patients were more likely to present with polymicrobial infection (odds ratio [OR] 3.4, P = 0.023), and polymicrobial infections were associated with multidrug-resistant organisms (P = 0.018). Smoking, drug use, HIV positivity, prior corneal pathology, and contact lens use were not associated with an increased risk of polymicrobial infection. Eleven patients (6.3%) were started on topical antibiotics before presentation; of these, none developed polymicrobial infections or multidrug-resistant organisms. Polymicrobial infections increased the likelihood to initiation of fortified antibiotics (OR 2.9, P = 0.011) but did not impact ulcer size, final visual acuity, time to resolution, or likelihood of emergent procedures.

Conclusions:
Homelessness correlates with an increased risk of polymicrobial keratitis and subsequent multidrug resistance, supporting initiation of broad antibiotic coverage in this population. Prior topical antibiotics did not increase risk of polymicrobial infection. Polymicrobial infection did not significantly worsen clinical outcomes.
Motor and Sensory Balance Deficits in Individuals Immediately After COVID-19, a Cohort Study
Authors: Wrisley Diane M. , Garavito Eder A. , Jones Brittany , Klintworth-Kirk Tamara , Poole Ashley K. 
Published: September 2023

Background and Purpose:
Individuals with cardiorespiratory dysfunction demonstrate postural instability and increased risk of falls. Given that coronavirus disease (COVID-19) is commonly defined as a respiratory condition, it could be presumed that these patients may demonstrate similar balance deficits. This study aimed to determine deficits and characterize balance dysfunction (sensory or motor) in hospitalized patients classified as “COVID-19 recovered.”

Methods:
Twenty-five participants consented for this study. Participants completed the Activity-Specific Balance Confidence Scale (ABC), a questionnaire about dizziness, the Timed “Up & Go” (TUG), and the modified Clinical Test of Sensory Interaction and Balance in a single session. The percentage of subjects who scored abnormal on the outcome measures was calculated. Correlations between demographics, respiratory function, and clinical outcome measures were determined using Spearman correlation coefficient.

Results:
All participants had abnormal scores on the TUG, 88% had abnormal scores on the ABC, and 48% of the subjects had abnormal scores on standing on foam eyes closed indicating difficulty using vestibular information. No correlation coefficient above 0.50 was found between the demographic information, respiratory function, and clinical outcome measures.

Discussion:
Clinical outcome measure scores did not correlate with respiratory function indicating that the deficits may be due to the extrapulmonary components of COVID-19.

Conclusion:
Both young and older adults presented with motor and sensory balance deficits acutely after COVID-19 infection. It is recommended that individuals acutely post–COVID-19 receive education and interventions to increase mobility, improve balance, decrease fall risk, and specifically receive activities that stimulate the vestibular system.
Daily Summer Temperatures and Hospitalization for Acute Cardiovascular Events: Impact of Outdoor PM2.5 Oxidative Potential on Observed Associations Across Canada
Authors: Weichenthal Scott , Lavigne Eric , You Hongyu , Pollitt Krystal , Shin Tim , Kulka Ryan , Stieb Dave M. , Hatzopoulou Marianne , Evans Greg , Burnett Richard T. 
Published: September 2023

Background:
Oxidative stress plays an important role in the health impacts of both outdoor fine particulate air pollution (PM2.5) and thermal stress. However, it is not clear how the oxidative potential of PM2.5 may influence the acute cardiovascular effects of temperature.

Methods:
We conducted a case–crossover study of hospitalization for cardiovascular events in 35 cities across Canada during the summer months (July–September) between 2016 and 2018. We collected three different metrics of PM2.5 oxidative potential each month in each location. We estimated associations between lag-0 daily temperature (per 5ºC) and hospitalization for all cardiovascular (n = 44,876) and ischemic heart disease (n = 14,034) events across strata of monthly PM2.5 oxidative potential using conditional logistical models adjusting for potential time-varying confounders.

Results:
Overall, associations between lag-0 temperature and acute cardiovascular events tended to be stronger when outdoor PM2.5 oxidative potential was higher. For example, when glutathione-related oxidative potential (OPGSH) was in the highest tertile, the odds ratio (OR) for all cardiovascular events was 1.040 (95% confidence intervals [CI] = 1.004, 1.074) compared with 0.980 (95% CI = 0.943, 1.018) when OPGSH was in the lowest tertile. We observed a greater difference for ischemic heart disease events, particularly for older subjects (age >70 years).

Conclusions:
The acute cardiovascular health impacts of summer temperature variations may be greater when outdoor PM2.5 oxidative potential is elevated. This may be particularly important for ischemic heart disease events.
Inpatient versus Outpatient Immediate Alloplastic Breast Reconstruction: Recent Trends, Outcomes, and Safety
Authors: Little Andrea K. , Patmon Darin L. , Sandhu Harminder , Armstrong Shannon , Anderson Daniella , Sommers Megan 
Published: September 2023

Background:
Immediate alloplastic breast reconstruction was traditionally performed as an inpatient procedure. Despite several reports in the literature demonstrating comparable safety outcomes, there remains hesitancy to accept breast reconstruction performed as an outpatient procedure.

Methods:
A retrospective review of National Surgical Quality Improvement Program data from 2014 to 2018 was utilized to evaluate recent trends and 30-day postoperative complication rates for inpatient versus outpatient immediate prosthetic-based breast reconstruction. Propensity score matching was used to obtain comparable groups.

Results:
During the study period, 33,587 patients underwent immediate alloplastic breast reconstruction. Of those, 67.5% of patients were discharged within 24 hours, and 32.4% of patients had a hospital stay of more than 24 hours. Immediate alloplastic reconstruction had an overall growth rate of 16.9% from 2014 to 2018. After propensity score matching, intraoperative variables that correlated with significantly increased inpatient status included increased work relative value units (16.3 ± 2.3 versus 16.2 ± 2.6; P < 0.001), longer operative times (228 ± 86 versus 206 ± 77; P < 0.001), and bilateral procedure (44.0% versus 43.5%; P < 0.001). There were higher rates of pulmonary embolism, wound dehiscence, urinary tract infection, transfusions, sepsis, readmissions, and reoperations in the group with the longer hospital stay.

Conclusion:
Based on increased complication rates and costs in the inpatient setting, we propose outpatient reconstructive surgery as a safe and cost-effective alternative for immediate alloplastic breast reconstruction.
Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: To what extent and under what conditions is normal alkaline phosphatase level associated with complication-free survival gain?
Authors: Corpechot Christophe , Lemoinne Sara , Soret Pierre-Antoine , Hansen Bettina , Hirschfield Gideon , Gulamhusein Aliya , Montano-Loza Aldo J. , Lytvyak Ellina , Pares Albert , Olivas Ignasi , Eaton John E. , Osman Karim T. , Schramm Christoph , Sebode Marcial , Lohse Ansgar W. , Dalekos George , Gatselis Nikolaos , Nevens Frederik , Cazzagon Nora , Zago Alessandra , Russo Francesco Paolo , Floreani Annarosa , Abbas Nadir , Trivedi Palak , Thorburn Douglas , Saffioti Francesca , Barkai Laszlo , Roccarina Davide , Calvaruso Vicenza , Fichera Anna , Delamarre Adèle , Sobenko Natalia , Villamil Alejandra Maria , Medina-Morales Esli , Bonder Alan , Patwardhan Vilas , Rigamonti Cristina , Carbone Marco , Invernizzi Pietro , Cristoferi Laura , van der Meer Adriaan , de Veer Rozanne , Zigmond Ehud , Yehezkel Eyal , Kremer Andreas E. , Deibel Ansgar , Bruns Tony , Große Karsten , Wetten Aaron , Dyson Jessica Katharine , Jones David , Dumortier Jérôme , Pageaux Georges-Philippe , de Lédinghen Victor , Chazouillères Olivier , Carrat Fabrice ,   the Global & ERN Rare-Liver PBC Study Groups
Published: September 2023

Background and Aims:
Normal alkaline phosphatase (ALP) levels in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC) are associated with better long-term outcome. However, second-line therapies are currently recommended only when ALP levels remain above 1.5 times the upper limit of normal (×ULN) after 12-month UDCA. We assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains.

Approach and Results:
We performed a retrospective cohort study of 1047 patients with PBC who attained an adequate response to UDCA according to Paris-2 criteria. Time to liver-related complications, liver transplantation, or death was assessed using adjusted restricted mean survival time (RMST) analysis. The overall incidence rate of events was 17.0 (95% CI: 13.7–21.1) per 1000 out of 4763.2 patient-years. On the whole population, normal serum ALP values (but not normal gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST); or total bilirubin < 0.6 ×ULN) were associated with a significant absolute complication-free survival gain at 10 years (mean 7.6 months, 95% CI: 2.7 - 12.6 mo.; p = 0.003). In subgroup analysis, this association was significant in patients with a liver stiffness measurement ≥ 10 kPa and/or age ≤ 62 years, with a 10-year absolute complication-free survival gain of 52.8 months (95% CI: 45.7–59.9, p < 0.001) when these 2 conditions were met.

Conclusions:
PBC patients with an adequate response to UDCA and persistent ALP elevation between 1.1 and 1.5 ×ULN, particularly those with advanced fibrosis and/or who are sufficiently young, remain at risk of poor outcome. Further therapeutic efforts should be considered for these patients.
Canonical Wnt signaling promotes HSC glycolysis and liver fibrosis through an LDH-A/HIF-1α transcriptional complex
Authors: Wang Feixia , Chen Li , Kong Desong , Zhang Xiaojin , Xia Siwei , Liang Baoyu , Li Yang , Zhou Ya , Zhang Zili , Shao Jiangjuan , Zheng Shizhong , Zhang Feng 
Published: September 2023

Background and Aims:
Aerobic glycolysis reprogramming occurs during HSC activation, but how it is initiated and sustained remains unknown. We investigated the mechanisms by which canonical Wnt signaling regulated HSC glycolysis and the therapeutic implication for liver fibrosis.

Approach and Results:
Glycolysis was examined in HSC-LX2 cells upon manipulation of Wnt/β-catenin signaling. Nuclear translocation of lactate dehydrogenase A (LDH-A) and its interaction with hypoxia-inducible factor-1α (HIF-1α) were investigated using molecular simulation and site-directed mutation assays. The pharmacological relevance of molecular discoveries was intensified in primary cultures, rodent models, and human samples. HSC glycolysis was enhanced by Wnt3a but reduced by β-catenin inhibitor or small interfering RNA (siRNA). Wnt3a-induced rapid transactivation and high expression of LDH-A dependent on TCF4. Wnt/β-catenin signaling also stimulated LDH-A nuclear translocation through importin β2 interplay with a noncanonical nuclear location signal of LDH-A. Mechanically, LDH-A bound to HIF-1α and enhanced its stability by obstructing hydroxylation-mediated proteasome degradation, leading to increased transactivation of glycolytic genes. The Gly28 residue of LDH-A was identified to be responsible for the formation of the LDH-A/HIF-1α transcription complex and stabilization of HIF-1α. Furthermore, LDH-A-mediated glycolysis was required for HSC activation in the presence of Wnt3a. Results in vivo showed that HSC activation and liver fibrosis were alleviated by HSC-specific knockdown of LDH-A in mice. β-catenin inhibitor XAV-939 mitigated HSC activation and liver fibrosis, which were abrogated by HSC-specific LDH-A overexpression in mice with fibrosis.

Conclusions:
Inhibition of HSC glycolysis by targeting Wnt/β-catenin signaling and LDH-A had therapeutic promise for liver fibrosis.
Spatial proteomics of immune microenvironment in nonalcoholic steatohepatitis-associated hepatocellular carcinoma
Authors: Li Meiyi , Wang Lina , Cong Liang , Wong Chi Chun , Zhang Xiang , Chen Huarong , Zeng Tao , Li Bin , Jia Xian , Huo Jihui , Huang Yuhua , Ren Xiaoxue , Peng Sui , Fu Guo , Xu Lixia , Sung Joseph J.Y. , Kuang Ming , Li Xiaoxing , Yu Jun 
Published: September 2023

Background and Aims:
NASH-HCC is inherently resistant to immune checkpoint blockade, but its tumor immune microenvironment is largely unknown.

Approach and Results:
We applied the imaging mass cytometry to construct a spatially resolved single-cell atlas from the formalin-fixed and paraffin-embedded tissue sections from patients with NASH-HCC, virus-HCC (HBV-HCC and HCV-HCC), and healthy donors. Based on 35 biomarkers, over 750,000 individual cells were categorized into 13 distinct cell types, together with the expression of key immune functional markers. Higher infiltration of T cells, myeloid-derived suppressor cell (MDSCs), and tumor-associated macrophages (TAMs) in HCC compared to controls. The distribution of immune cells in NASH-HCC is spatially heterogeneous, enriched at adjacent normal tissues and declined toward tumors. Cell-cell connections analysis revealed the interplay of MDSCs and TAMs with CD8+ T cells in NASH-HCC. In particular, exhausted programmed cell death 1 (PD-1+)CD8+ T cells connected with programmed cell death-ligand 1 (PD-L1+)/inducible T cell costimulator (ICOS+) MDSCs and TAMs in NASH-HCC, but not in viral HCC. In contrast, CD4+/CD8+ T cells with granzyme B positivity were reduced in NASH-HCC. Tumor cells expressed low PD-L1 and showed few connections with immune cells.

Conclusions:
Our work provides the first detailed spatial map of single-cell phenotypes and multicellular connections in NASH-HCC. We demonstrate that interactions between MDSCs and TAMs with effector T cells underlie immunosuppression in NASH-HCC and are an actionable target.
National prevalence estimates for steatotic liver disease and subclassifications using consensus nomenclature
Authors: Lee Brian P. , Dodge Jennifer L. , Terrault Norah A. 
Published: September 2023

Background and Aims:The multisociety consensus nomenclature has renamed NAFLD to steatotic liver disease (SLD) with various subclassifications. There is a paucity of data regarding how the new nomenclature modifies our understanding of disease prevalence and patient phenotypes.Approach and Results:Using the National Health and Nutrition Examination Survey from January 2017 to March 2020, we included all participants aged 18 years or above with complete vibration-controlled transient elastography measures. SLD and its subclassifications [metabolic dysfunction-associated SLD (MASLD), MASLD + increased alcohol intake (MetALD), alcohol-associated liver disease (ALD), etiology-specific/cryptogenic] were defined according to consensus nomenclature. National SLD prevalence and subclassifications were estimated, and among key subgroups [age, sex, race/ethnicity, advanced liver fibrosis (liver stiffness measurement [LSM] ≥11.7 kPa)]. Among 7367 participants, 2549 had SLD (mean age 51 y, 57.7% male, 63.2% non-Hispanic White). The estimated prevalence of SLD was 34.2% (95% CI 31.9%–36.5%): MASLD 31.3% (29.2%–33.4%), MetALD 2% (1.6%–2.9%), ALD 0.7% (0.5–0.9%), etiology-specific/cryptogenic 0.03% (0.01%–0.08%). In exploratory analyses, participants classified as non-SLD with (vs. without) advanced fibrosis had a higher mean number of metabolic risk factors [2.7 (2.3–3.1) vs. 2.0 (1.9–2.0)] and a higher proportion with average alcohol use ≥20 g/d (women)/≥30 g/d (men) [20.9% (6.2%–51.3%) vs. 7.2% (6.1%–8.4%)]. In another exploratory analysis, increasing quantities of alcohol use remaining below the threshold for MASLD + increased alcohol intake were associated with advanced liver fibrosis in men, but not women. There was 99% overlap in cases of NAFLD and MASLD.Conclusions:Our findings highlight the utility of the new consensus nomenclature to address deficiencies present with the old nomenclature, and identify areas that require research to further refine classifications of SLD.