bluuebunny/crossref_metadata_2025_split huggingface dataset:
A241 AMOXICILLIN-CLAVULANATE INDUCED LIVER INJURY WITH CONCOMITANT AMPULLARY STENOSIS: A CASE REPORT AND LITERATURE REVIEW
Authors: Kecskemeti K , Gibbings N , Fung S 
Published: February 2025

Abstract

Background
Amoxicillin-clavulanate drug-induced liver injury (DILI) has been reported at a rate of 1 in 2,400 prescriptions1. Patients tend to present with a cholestatic pattern of liver enzyme elevation while hepatocellular enzyme elevation is more commonly reported in younger patients. In mild cases, once amoxicillin-clavulanate is discontinued the patient’s recovery tends to be rapid.

Aims
We present a patient case and a literature review regarding concomitant ampullary stenosis and amoxicillin-clavulanate induced liver injury.

Methods
We present a case report outlining a patient’s course and management in hospital. We then conducted a literature review on Pub-Med using the following terms: “ampulla stenosis” and “drug-induced liver injury”.

Results
A 56-year-old female with a remote history of a cholecystectomy was prescribed amoxicillin-clavulanate for suspected diverticulitis. She completed a 5-day course and then represented with worsening abdominal pain. She was found to have significant transaminitis with a mixed cholestatic-hepatocellular pattern (ALT 726, AST 351, ALP 289). She underwent an MRCP which showed extensive extrahepatic and intrahepatic biliary duct dilations which was disproportionate to expected post-cholecystectomy changes and suggestive of ampullary stenosis. Amoxicillin-clavulanate was discontinued on admission and her liver enzymes normalized as an out-patient three weeks after admission (ALT 34, ALP 125). She was referred for outpatient endoscopic ultrasound for assessment and treatment of her ampullary stenosis.
The literature review on PubMed yielded a single case report (n = 1) of a patient with atorvastatin induced liver injury and underlying ampullary stenosis2. In that case, the patient improved when the medication was discontinued and then underwent a sphincterotomy.

Conclusions
Although seldomly reported in the medical literature there is one other case report of concomitant drug-induced liver injury in a patient with ampullary stenosis. To our knowledge, this is the first case report of amoxicillin-clavulanate induced liver injury in a patient with ampullary stenosis. Potential mechanisms may include ampullary stenosis related biliary stasis which may exacerbate the toxic effects of medications on the liver.
Patient’s Biochemical Investigations in Hospital

Note: AST was not measured on July 30th. INR was not recorded during the patient’s hospitalization

Funding Agencies
NoneN/A
A242 SCLEROSING MESENTERITIS OF THE PORTA HEPATIS PRESENTING AS CHOLANGIOCARCINOMA WITH RECURRENT CHYLOUS ASCITES AND GASTRIC OUTLET OBSTRUCTION
Authors: Hoang T T , Karavelic A , Sunil A , Murray T , Telford J , Clement E , Gador A 
Published: February 2025

Abstract

Background
Sclerosing mesenteritis (SM) is characterized by chronic fibroinflammatory infiltration of the abdominal mesentery. While commonly affecting the small bowel, we present the first reported case of SM mimicking hilar cholangiocarcinoma by involving the porta hepatis, resulting in chylous ascites, gastric outlet obstruction, and duodenal perforation.

Aims
To broaden recognition of this rare disease and expand literature on treatment options

Methods
Case report and literature review

Results
A 59-year-old man with previous alcoholic pancreatitis presented with one month of progressive abdominal pain and distension. He was found to have large volume chylous ascites and a hilar mass on computed tomography scan. Magnetic resonance cholangiopancreatography confirmed a soft tissue density at the porta hepatis with intra- and extrahepatic duct dilation. Endoscopic ultrasound (EUS) revealed a soft tissue mass and biopsies showed a chronic lymphohistiocytic infiltrate but no malignancy. Positron emission tomography, liver biopsy, and bidirectional endoscopy were unrevealing. Serial large-volume paracenteses were performed for comfort, though portal hypertension was ruled out via transjugular measurements. One month into hospitalization, he developed gastric outlet obstruction from extrinsic mass and required nasojejunal feeding. This was complicated by a contained duodenal perforation managed non-operatively. Palliative dexamethasone was started for presumed cholangiocarcinoma which entirely resolved his symptoms. He was discharged after three months but represented off steroids with recurrent ascites and gastric outlet obstruction. Diagnostic laparoscopy was negative. EUS-guided biopsy again showed the same chronic inflammatory infiltrate. He was diagnosed with SM and started on oral prednisone which resolved his symptoms. He remains in remission as an outpatient on colchicine, tamoxifen, and low-dose prednisone.

Conclusions
SM is a rare disease characterized by chronic mesenteric inflammation, fibrosis, and fat necrosis. While 10% of cases are incidental findings, complications occur in 24% of patients and include recurrent chylous ascites, small bowel obstruction, and intestinal perforation. Diagnosis is challenging given non-specific findings but can be made on histology and radiology. This benign disease is often mistaken for malignancy, resulting in unnecessary diagnostic tests. To our knowledge, this is only the second reported case of hilar SM, and the first to present with the aforementioned complications. Treatment includes prednisone and tamoxifen, with colchicine, azathioprine, or thalidomide used as steroid-sparing agents. Increased recognition of this entity will help avoid unnecessary diagnostic interventions and inform options for medical therapy.

Funding Agencies
None
A247 ACTIVATION OF VISCERAL AFFERENT NEURONS INVOLVED IN NOCICEPTION BY A BACTERIUM ASSOCIATED WITH INFLAMMATORY BOWEL DISEASE
Authors: Nakhle R , Wood H M , Baker C C , Reed D E , Lomax A E 
Published: February 2025

Abstract

Background
Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammation of the gastrointestinal tract. Severe abdominal pain is a common symptom of IBD, yet effective pain treatments are limited. Proteolytic activity is elevated in IBD compared to healthy individuals. Recently, protease production by the gut bacterium Bacteroides vulgatus has been correlated with the severity of IBD.

Aims
Since proteases acting on protease-activated receptor 2 (PAR-2) can activate visceral pain pathways, we test the hypothesis that mediators from B. vulgatus activate visceral pain pathways and can directly activate dorsal root ganglia (DRG) neurons, altering pain signalling.

Methods
The effects of B. vulgatus ATCC 8482 supernatant or brain heart infusion (BHI) growth media on nociceptive neurons were assessed using ex-vivo single-unit afferent nerve recordings from C57bl/6 mouse colons. To further examine cellular mechanisms, Ca2+ imaging was performed on dissociated DRG neurons following the superfusion of B. vulgatus culture supernatant. As TRPV1 is an ion channel expressed mainly on nociceptive neurons, the effect of B vulgatus culture supernatant on Ca2+ influx in response to the TRPV1 agonist capsaicin was also quantified. “N” represents mice, while “n” represents single afferent units or DRG neurons.

Results
Perfusion of B. vulgatus supernatant (1:20) through the lumen of murine colons significantly increased basal firing frequency by 50% (p &lt; 0.001, N = 8, n = 38) and mechanosensitivity of colonic afferent axons by 48% (p &lt; 0.05, N = 8). Interestingly, only the putative nociceptor high-threshold units were activated upon perfusion of this bacterial supernatant (p &lt; 0.01, N = 8, n = 13), while the wide-dynamic range units were unaffected (p &gt; 0.05, N = 8, n = 30). The BHI growth media did not alter basal activity (p &gt; 0.05, N = 6, n = 23) or afferent nerve mechanosensitivity (p &gt; 0.05, N = 6). Superfusion of B. vulgatus supernatant (1:100) increased intracellular [Ca2+] by 16% (p &lt; 0.0001, N= 7, n = 51). Furthermore, exposure to the B. vulgatus supernatant significantly elevated Ca2+ influx in response to the TRPV1 agonist capsaicin (100 nM; p &lt; 0.0001, n = 77, N = 7), while the BHI media did not alter intracellular [Ca2+] in response to capsaicin (p &gt; 0.05, n = 66, N = 7).

Conclusions
Mediators released by Bacteroides vulgatus can activate visceral afferent nerves involved in nociception. Additionally, B. vulgatus can directly modulate DRG neuronal Ca2+ homeostasis and sensitize TRPV1 in these neurons. Future studies will explore whether proteases are responsible.

Funding Agencies
CIHR
A249 PROTON PUMP INHIBITOR USE AND RISK OF DEMENTIA: AN UMBRELLA REVIEW OF SYSTEMATIC REVIEWS AND META-ANALYSES
Authors: Abu-Mallouh B E , Al-Naamani K , Martel M , Barkun A 
Published: February 2025

Abstract

Background
Clinical studies about the association between long term PPI use and dementia have been inconsistent, with systematic reviews and meta-analyses (SR/MA) reaching disparate conclusions.

Aims
This umbrella review of SR/MA attempts to clarify the current understanding of any possible association linking PPI use to dementia.

Methods
We searched Embase, Medline, CENTRAL and ISI Web of Science for fully published SR/MA in English up to June 2024 using controlled vocabulary and text words ((1) proton pump and (2) dementia (dementia and mild cognitive impairment, Alzheimer disease)). SR/MA methodological quality was scored using the AMSTAR-2 tool.

Results
Eleven SR/MA published (May 2016 - February 2023) described 21 studies (one randomized trial). Only one high-quality SR/MA significantly associated PPI use with dementia. None of six SR/MA investigating PPI use and Alzheimer’s disease showed a significant association. Significant associations with dementia in subgroup analyses were found in one SR/MA each for older patients (age &gt; 65 years) (HR=1.39 (1.17;1.65)), long term PPI use (&gt; 5 years) (HR=1.28 (1.12; 1.46)), short term PPI use (&lt; 5 years) (RR=1.62 (1.40–1.86)), when only considering higher quality studies (RR=1.54 (1.12; 2.13)), and amongst European populations (HR=1.46 (1.23–1.73)). Two SR/MA found an association when only assessing prospective cohort studies (RR=1.36 (1.19; 1.55)), (RR=1.44 (1.36; 1.52)).

Conclusions
Most SR/MA suggest no link between PPI use and dementia. Only properly designed, adequately powered randomized trials can rule out a small but significant association possibly linking PPI use to dementia.

N = study number in SR/MA, HR = hazards ratio, RR = relative risk, OR = odds ratio, NA = Not applicable

Funding Agencies
None
A251 EOSINOPHILIC ESOPHAGITIS IN AN END-STAGE ACHALASIA PATIENT
Authors: Pan S , Woodman K 
Published: February 2025

Abstract

Background
Achalasia is a rare motility disorder involving abnormal esophageal motility and impaired lower esophageal sphincter relaxation. A growing number of reports have identified esophageal eosinophilia levels consistent with eosinophilic esophagitis (EoE) in achalasia patients, suggesting a possible pathophysiological association between both conditions that may yield clinical significance for diagnosis and treatment.

Aims
The aim of the present report is to highlight this association, through the case of a Type 1 Achalasia patient whose mid-esophageal biopsies were significant for concurrent EoE.

Methods
The case and its associated figures were compiled from the patient’s medical records following informed consent.

Results
A 38-year-old gentleman was referred to our motility service for manometric assessment. The patient suffered from a 4-5 year history of persistent, progressively worsening dysphagia, recurrent regurgitation and weight loss. Endoscopic assessment prior to assessment by our service was significant for EoE. Manometry patterns were consistent with Type 1 achalasia, though it was unclear whether this had developed prior to or after the patient’s EoE. The patient’s symptoms continued to progress in the months after his achalasia diagnosis, despite proton pump inhibitor therapy, steroid therapy and an elimination diet. He was ultimately referred to the General Surgery service in Hamilton, Ontario for completion of a Heller Myotomy. The post-operative course was uncomplicated, and he was able to return to an oral diet shortly afterwards, with some lingering dyspepsia but no further dysphagia or regurgitative symptoms.

Conclusions
The present case supports pre-existing reports in the literature that achasia and EoE can happen concurrently, and that a pathophysiological correlation may be involved, notably regarding the inflammatory processes in EoE and how they might contribute to esophageal neuronal damage. Continued research is needed to better understand this relationship.

Esophageal pressure topography plots taken from high-resolution manometry performed on April 18, 2023, representing the average pressure patterns of successful swallows during the endoscopic procedure. Highlighted is the relaxation of the upper esophageal sphincter during initiation of the swallow (A), along with the absence of peristaltic pressures along the length of the esophagus (B) in the setting of incomplete deglutitive relaxation of the lower esophageal sphincter (C), consistent with type 1 achalasia.

Funding Agencies
None
Mechanisms and Manifestations of Group B Streptococcus Meningitis in Newborns
Authors: Alexander Natalie G , Cutts William D , Hooven Thomas A , Kim Brandon J 
Published: February 2025

Abstract
Group B Streptococcus (GBS; Streptococcus agalactiae) is a gram-positive colonizer of the healthy intestinal and genitourinary microbiota. During and shortly after birth, neonates and infants can be opportunistically infected leading to sepsis, pneumonia, or meningitis among other illnesses. GBS is the leading cause of neonatal meningitis globally, and while prophylactic treatments have been successful for reducing early-onset disease, no decrease in the incidence of late-onset disease has occurred and no vaccine is currently available. In this review, we describe GBS both from a clinical and molecular standpoint. We first describe the history of GBS perinatal disease and its clinical presentation and treatment, as well as patient outcomes. We then present recently discovered GBS interactions at the blood–brain barrier that contribute to disease and inflammatory responses, and efforts to develop a broadly effective GBS vaccine.
Configuration of single giant planet systems generating ‘Oumuamua-like interstellar asteroids
Authors: Zheng Xi-Ling , Zhou Ji-Lin 
Published: February 2025

ABSTRACT
The first discovered interstellar small object, ‘Oumuamua (1I/2017 U1), presents unique physical properties of extremely elongated geometric shape and dual characteristics of an asteroid and a comet. These properties suggest a possible origin through tidal fragmentation, which posits that ‘Oumuamua was produced through intensive tidal fragmentation during a close encounter with a star or a white dwarf, resulting in its shape and ejection from its natal system. According to this mechanism, a high initial orbit eccentricity and a small pericentre of the parent body are necessary to produce ‘Oumuamua-like objects. To verify whether this mechanism can occur in single giant planet systems, we conduct long-term numerical simulations of systems with a low-mass ($0.5\,M_\odot$) host star and a giant planet in this study. We determine that an eccentric orbit ($e_\text{p}\sim 0.2$) and a Jupiter-mass ($M_\text{p}\sim M_\text{J}$) of the planet appears to be optimal to generate sufficient perturbations for the production of ‘Oumuamua-like objects. When the planetary semi-major axis $a_\text{p}$ increases, the proportion of planetesimals ejected beyond the system $P(\text{ej})$ increases accordingly, while the possibilities of ejected planetesimals undergoing stellar tidal fragmentation $P(\text{tidal}|\text{ej})$ remains relatively constant at $\sim 0.6~{{\ \rm per\ cent}}$. Focusing on stellar tidal fragmentation alone, the ratio of extremely elongated interstellar objects to all interstellar objects is $P_\text{e}\sim 3~{{\ \rm per\ cent}}$.
On the origin of metal species in the human brain: a perspective on key physicochemical properties
Authors: Brooks Jake , Everett James , Sadler Peter J , Telling Neil , Collingwood Joanna F 
Published: February 2025

Abstract
Normal functioning of the human brain is dependent on adequate regulation of essential metal nutrients. However, it is also highly sensitive to metal-mediated toxicity, linked to various neurodegenerative disorders. Exposure to environmental metal sources (especially to particulate air pollution) can stimulate toxicity and neuropathologic effects, which is particularly evident in populations chronically exposed to high levels of air pollution. Identifying the sources of metal-rich deposits in the human brain is important in not only distinguishing the effects of environmentally-acquired metals from endogenous metal dysregulation, but also for tracing pollutant sources which may be subject to exposure control. This perspective reviews evidence for key physicochemical properties (size/morphology, chemical composition, oxidation state, magnetic properties and isotopic composition) concerning their capacity to distinguish sources of metals in the brain. The scope for combining analytical techniques to study properties in tandem is also discussed.
Plant PI-PLC signaling in stress and development
Authors: Laxalt Ana M , van Hooren Max , Munnik Teun 
Published: February 2025

Abstract
Phosphoinositide-specific phospholipase C (PI-PLC) signaling is involved in various plant stress and developmental responses. Though several aspects of this lipid signaling pathway are conserved within animals and plants, clear differences have also emerged. While animal PLC signaling is characterized by the hydrolysis of PIP2 and production of IP3 and DAG as second messengers to activate Ca2+ and PKC signaling, plant PI-PLCs seem to predominantly use PIP as substrate and convert IP2 and DAG into inositolpolyphosphates and phosphatidic acid (PA) as plant second messengers. Sequencing of multiple plant genomes confirmed that plant PLC signaling evolved differently from animals, lacking homologs of the IP3 gated-Ca2+ channel, PKC and TRP channels, and with PLC enzymes resembling the PLCζ subfamily, which lacks the conserved PH domain that binds PIP2. With emerging tools in plant molecular biology, data analyses, and advanced imaging, plant PLC signaling is ready to gain momentum.
Ceramide-1-phosphate enhances defense responses against Sclerotinia sclerotiorum in Brassica napus
Authors: Ouyang Zhewen , Tan Zengdong , Ali Usman , Zhang Ying , Li Bo , Yao Xuan , Yang Bao , Guo Liang 
Published: February 2025

Abstract
Sclerotinia stem rot caused by Sclerotinia sclerotiorum is one of the most severe diseases affecting the growth and production of Brassica napus. Sphingolipid metabolism plays a crucial role in plant response to pathogens. In this study, we show that ceramide kinase (CERK) is significantly induced during S. sclerotiorum infection to produce higher levels of ceramide-1-phosphate (C1P) in B. napus. The balance between ceramide (Cer) and C1P affects plant resistance to S. sclerotiorum, with CERK mutant lines exhibiting greater susceptibility to S. sclerotiorum and CERK overexpression lines showing enhanced resistance to this pathogen. Moreover, we identified candidate C1P-binding proteins by proteomic analysis and determined that C1P binds to and promotes the activity of a Gly–Asp–Ser–Leu lipase protein involved in B. napus resistance to S. sclerotiorum infection. In conclusion, our results indicate that C1P plays a key role in S. sclerotiorum resistance through metabolic regulation and signal transduction in B. napus.
Development and Validation of a Machine Learning Prediction Model for Textbook Outcome in Liver Surgery: Results From a Multicenter, International Cohort
Authors: Wang Jane , Ashraf Ganjouei Amir , Hibi Taizo , Lluis Nuria , Gomes Camilla , Romero-Hernandez Fernanda , Yin Han , Calthorpe Lucia , Okamura Yukiyasu , Abe Yuta , Tanaka Shogo , Tanabe Minoru , Morise Zeniche , Asbun Horacio , Geller David , Abu Hilal Mohammed , Adam Mohamed , Alseidi Adnan ,   International Hepatectomy Study Group
Published: February 2025

Objective:
This study aimed to (1) develop a machine learning (ML) model that predicts the textbook outcome in liver surgery (TOLS) using preoperative variables and (2) validate the TOLS criteria by determining whether TOLS is associated with long-term survival after hepatectomy.

Background:
Textbook outcome is a composite measure that combines several favorable outcomes into a single metric and represents the optimal postoperative course. Recently, an expert panel of surgeons proposed a Delphi consensus-based definition of TOLS.

Methods:
Adult patients who underwent hepatectomies were identified from a multicenter, international cohort (2010–2022). After data preprocessing and train-test splitting (80:20), 4 models for predicting TOLS were trained and tested. Following model optimization, the performance of the models was evaluated using receiver operating characteristic curves, and a web-based calculator was developed. In addition, a multivariable Cox proportional hazards analysis was conducted to determine the association between TOLS and overall survival (OS).

Results:
A total of 2059 patients were included, with 62.8% meeting the criteria for TOLS. The XGBoost model, which had the best performance with an area under the curve of 0.73, was chosen for the web-based calculator. The most predictive variables for having TOLS were a minimally invasive approach, fewer lesions, lower Charlson Comorbidity Index, lower preoperative creatinine levels, and smaller lesions. In the multivariable analysis, having TOLS was associated with improved OS (hazard ratio = 0.82, P = 0.015).

Conclusions:
Our ML model can predict TOLS with acceptable discrimination. We validated the TOLS criteria by demonstrating a significant association with improved OS, thus supporting their use in informing patient care.
Evaluation of Diversity, Equity, and Inclusion Perceptions in the Orthopedic Surgery Workforce: A Stratified Approach
Authors: Bousleiman Jamie , Lutnick Ellen , Spath Alexandra , Wells Jeremy , Daoust Susan , Nader Nader D. 
Published: February 2025

Introduction:
By stratifying perceptions of importance of diversity, equity and inclusion from orthopedic staff, this research aims to guide effective initiatives centered around DEI.

Materials & Methods:
A prospective survey study was distributed to a metropolitan university-based Orthopedic Surgery Department. Chi square analysis was used to compare perception of personal and professional experiences, health, gender and sexual identity between age, gender, ethnicity, level of education, socioeconomic status in childhood, and household income of respondents.

Results:
Of 111 respondents, 79.4% aged ≤35 saw apt diverse representation of their own professional experience versus 93.0% in the >35 age group (P value 0.020). 89.9% of females and 71.9% of males agreed on DEI’s importance, while 9.4% of males disagreed (P value 0.011). Level of education showed no significance. There was a significance between household income levels less than and greater than $70,000 in perceived importance of every category of DEI, including importance of diverse representation of personal/background experiences (race/ethnicity, religion, marital status, parental status, and SES as a child, P value 0.001), professional experiences (P value 0.013), personal health (P value 0.024), gender/sexual identity (P value 0.024), and importance of DEI in health care (P value 0.026). 56.7% respondents agreed to participate in DEI initiatives through the department.

Discussion and Conclusion:
Distinct variations related to perception of DEI were observed across demographics, particularly age, gender, and household income. Specific areas were identified, including gender and income differences, that require focused interventions. These findings provide insights for designing comprehensive and tailored DEI initiatives.