Hepatology Commons^™

Strategies To Enhance Diagnostic Capabilities For The New Drug-Resistant Tuberculosis (Dr-Tb) Drugs, Antonia Morita Iswari Saktiawati, Anca Vasiliu, Francesca Saluzzo, Onno W Akkerman

Faculty, Staff and Students Publications

The global burden of drug-resistant tuberculosis (DR-TB) continues to challenge healthcare systems worldwide. There is a critical need to tackle DR-TB by enhancing diagnostics and drug susceptibility testing (DST) capabilities, particularly for emerging DR-TB drugs. This endeavor is crucial to optimize the efficacy of new therapeutic regimens and prevent the resistance and overuse of these invaluable weapons. Despite this urgency, there remains a lack of comprehensive review of public health measures aimed at improving the diagnostics and DST capabilities. In this review, we outline strategies to enhance the capabilities, especially tailored to address the challenges posed by resistance to new …

Serum Levels Of Total Bile Acids Are Associated With An Increased Risk Of Hcc In Patients With Cirrhosis, Hashem B El-Serag, Aaron P Thrift, Hao Duong, Jing Ning, Saira Khaderi, Amit G Singal, Sumeet K Asrani, Jorge A Marrero, Hannah Powell, Kinza Rizwan, Omar Najjar, Christopher I Amos, Michelle Luster, Abeer Al-Sarraj, Emad Salem, Michael E Scheurer, Jagpreet Chhatwal, Salma Kaochar, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND: Previous studies have reported higher circulating bile acid levels in patients with HCC compared to healthy controls. However, the association between prediagnostic bile acid levels and HCC risk among patients with cirrhosis is unclear.

METHODS: We measured total BA (TBA) concentration in serum samples collected from a prospective cohort of patients with cirrhosis who were followed until the development of HCC, death, or last study date. Competing risk proportional hazard-adjusted models were used to estimate the association between tertiles of serum TBA levels and the risk of developing HCC. We quantified the incremental predictive value of serum bile acid …

Glp-1 Receptor Agonists And Risk For Cirrhosis And Related Complications In Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease, Fasiha Kanwal, Jennifer R Kramer, Liang Li, Yu-Xiao Yang, Yumei Cao, Xian Yu, Ronald Samuel, Basim Ali, Roxanne Desiderio, George Cholankeril, Mandeep Bajaj, Hashem B El-Serag, Steven M Asch

Faculty, Staff and Students Publications

IMPORTANCE: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasing cause of cirrhosis. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are effective in improving liver inflammation in patients with MASLD.

OBJECTIVE: To determine whether use of GLP-1 RAs is associated with lower risk of developing cirrhosis and its complications, including decompensation and hepatocellular cancer (HCC), among patients with MASLD.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study with an active comparator, new-user design used data from the national Veterans Health Administration Corporate Data Warehouse and Central Cancer Registry. Patients with MASLD and diabetes who were seen at 130 Veterans Health …

Neighborhood-Level Deprivation Mediates Racial And Ethnic Disparities In Hcc Diagnosis In Texas, Itunu O Sokale, Aaron P Thrift, Hashem B El-Serag, Abiodun O Oluyomi

Faculty, Staff and Students Publications

BACKGROUND: Texas has the highest HCC rates in the United States, and the greatest burden is among Hispanics. Racial and ethnic disparities in HCC incidence have multiple underpinning factors. We conducted a mediation analysis to examine the role of neighborhood disadvantage (Area Deprivation Index) as a potential mediator of the association between neighborhood race and ethnicity distribution and neighborhood HCC case counts in Texas.

METHODS: The primary outcome measure was counts of new HCC diagnoses per census tract based on Texas Department of State Health Services Texas Cancer Registry data. The primary exposure of interest was the race and ethnicity-based …

Hepatotoxicity Induced By Immune Checkpoint Inhibitors, Flaviu Muresan, Olga Hilda Orasan, Angela Cozma, Madalina Daiana Bancos, Lorena Ciumarnean, Mircea Vasile Milaciu, Tinca Codruta Pocol, Nicoleta Valentina Leach, Teodora Gabriela Alexescu, Ovidiu Vasile Fabian, George Ciulei, Mirela Georgiana Perne

Journal of Mind and Medical Sciences

Immune checkpoint inhibitors (ICIs) are an effective immunotherapeutic approach for cancers affecting the lung, skin, kidney, mammary gland, or certain hematologic malignancies. Regarding the prognosis of these oncological conditions, treatments with ICIs open new therapeutic perspectives with benefits for both patients and healthcare providers. A drawback of immune checkpoint inhibition is the occurrence of immune-related adverse events that can involve a wide range of organs, such as the liver. Given widespread usage of immunotherapy, the number of patients who suffer from this unwanted condition has increased. Hepatopathy induced by ICIs can be severe and can even lead to death. Detecting …

Genomic Biomarkers To Predict Response To Atezolizumab Plus Bevacizumab Immunotherapy In Hepatocellular Carcinoma: Insights From The Imbrave150 Trial, Sun Young Yim, Sung Hwan Lee, Seung-Woo Baek, Bohwa Sohn, Yun Seong Jeong, Sang-Hee Kang, Kena Park, Hyewon Park, Sunyoung S Lee, Ahmed O Kaseb, Young Nyun Park, Sun-Hee Leem, Michael A Curran, Ji Hoon Kim, Ju-Seog Lee

Faculty, Staff and Student Publications

Background/aims: Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge.

Methods: Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full …

Contemporary Epidemiology Of Hepatocellular Carcinoma: Understanding Risk Factors And Surveillance Strategies, Fouad Jaber, George Cholankeril, Hashem B El-Serag

Faculty, Staff and Students Publications

The contemporary epidemiology of hepatocellular carcinoma (HCC) shows a shift in the main etiological risk factors from less common but highly virulent (eg, hepatitis C and B) to more common but weak risk factors (eg, alcohol and metabolic syndrome). Therefore, we are in a seemingly paradoxical state of declining overall incidence rates of HCC-related to improved prevention and treatment of viral hepatitis but burgeoning number of people at an elevated risk of HCC. Several geographic regions have reported an increase in HCC attributable to alcoholic liver disease and metabolic dysfunction associated with steatotic liver disease (MASLD). The importance of risk …

Burden Of Mortality From Hepatocellular Carcinoma And Biliary Tract Cancers By Race And Ethnicity And Sex In Us, 2018–2023, Donghee Kim, Richie Manikat, Karn Wijarnpreecha, George Cholankeril, Aijaz Ahmed

Faculty, Staff and Students Publications

BACKGROUNDS/AIMS: The trends in mortality of hepatocellular carcinoma (HCC) and biliary tract cancers stratified by sex and race/ethnicity in the US continue to evolve. We estimated the sex- and race/ethnicity-based trends in HCC and biliary tract cancers-related mortality in US adults with a focus on disease burden.

METHODS: We performed a population-based analysis using the US national mortality records from 2018 to 2023. We identified HCC and biliary tract cancer using appropriate ICD-10 codes. Temporal trends in mortality were calculated by joinpoint analysis with annual percentage change (APC).

RESULTS: Annual age-standardized mortality from HCC decreased steadily with an APC of …

Transient Elastography And Diffusion-Weighted Magnetic Resonance Imaging For Assessment Of Liver Fibrosis In Children With Chronic Hepatitis C, Mohamed A El-Guindi, Alif A Allam, Ahmed A Abdel-Razek, Gihan A Sobhy, Menan E Salem, Mohamed A Abd-Allah, Mostafa M Sira

Faculty, Staff and Student Publications

BACKGROUND: Chronic hepatitis C (CHC) is a health burden with consequent morbidity and mortality. Liver biopsy is the gold standard for evaluating fibrosis and assessing disease severity and prognostic purposes post-treatment. Noninvasive alternatives for liver biopsy such as transient elastography (TE) and diffusion-weighted magnetic resonance imaging (DW-MRI) are critical needs.

AIM: To evaluate TE and DW-MRI as noninvasive tools for predicting liver fibrosis in children with CHC.

METHODS: This prospective cross-sectional study initially recruited 100 children with CHC virus infection. Sixty-four children completed the full set of investigations including liver stiffness measurement (LSM) using TE and measurement of apparent diffusion …

The Hcv-Melanoma Paradox: First Multi-Cohort And Molecular Net-Work Analysis Reveals Lower Incidence But Worse Outcomes—Integrating Clinical, Real-World, And In Silico Data, Essam Al Ageeli, Jawaher A. Abdulhakim, Mohammad H. Hussein, Maryam M. Alnoman, Samia S. Alkhalil, Peter P. Issa, Nader A. Nemr, Ahmed Abdelmaksoud, Dhaifallah A. Alenizi, Manal S. Fawzy, Eman A. Toraih

School of Medicine Faculty Publications

Background and Objectives: The relationship between hepatitis C virus (HCV) infection and melanoma remains poorly understood. This study aimed to investigate the association between HCV and melanoma, assess outcomes in patients with both conditions, and explore potential molecular mechanisms connecting the two diseases. Materials and Methods: We conducted a retrospective cohort study of 142 melanoma patients, including 29 with HCV-related cirrhosis, and analyzed their clinical outcomes. For external validation, we used the TriNetX Global Collaborative Network database, comprising 219,960 propensity-matched patients per group. An in silico analysis was performed to identify the molecular pathways linking HCV and melanoma. Results: In …

Gut Phageome In Mexican Americans: A Population At High Risk For Metabolic Dysfunction-Associated Steatotic Liver Disease And Diabetes, Suet-Ying Kwan, Caroline M Sabotta, Lorenzo R Cruz, Matthew C Wong, Nadim J Ajami, Joseph B Mccormick, Susan P Fisher-Hoch, Laura Beretta

Faculty, Staff and Student Publications

Mexican Americans are disproportionally affected by metabolic dysfunction-associated steatotic liver disease (MASLD), which often co-occurs with diabetes. Despite extensive evidence on the causative role of the gut microbiome in MASLD, studies determining the involvement of the gut phageome are scarce. In this cross-sectional study, we characterized the gut phageome in Mexican Americans of South Texas by stool shotgun metagenomic sequencing of 340 subjects, concurrently screened for liver steatosis by transient elastography. Inter-individual variations in the phageome were associated with gender, country of birth, diabetes, and liver steatosis. The phage signatures for diabetes and liver steatosis were subsequently determined. Enrichment of …

Tuberculosis Prevention: Current Strategies And Future Directions, Anca Vasiliu, Leonardo Martinez, Rishi K Gupta, Yohhei Hamada, Tara Ness, Alexander Kay, Maryline Bonnet, Martina Sester, Stefan H E Kaufmann, Christoph Lange, Anna M Mandalakas

Faculty, Staff and Students Publications

BACKGROUND: An estimated one fourth of the world's population is infected with Mycobacterium tuberculosis, and 5-10% of those infected develop tuberculosis in their lifetime. Preventing tuberculosis is one of the most underutilized but essential components of curtailing the tuberculosis epidemic. Moreover, current evidence illustrates that tuberculosis manifestations occur along a dynamic spectrum from infection to disease rather than a binary state as historically conceptualized. Elucidating determinants of transition between these states is crucial to decreasing the tuberculosis burden and reaching the END-TB Strategy goals as defined by the WHO. Vaccination, detection of infection, and provision of preventive treatment are key …

An Interdisciplinary Consensus Approach To Pulmonary Hypertension In Developmental Lung Disease, Nidhy P Varghese, Eric D Austin, Csaba Galambos, Mary P Mullen, Delphine Yung, R Paul Guillerman, Sara O Vargas, Catherine M Avitabile, Corey A Chartan, Nahir Cortes-Santiago, Michaela Ibach, Emma O Jackson, Jill Ann Jarrell, Roberta L Keller, Usha S Krishnan, Kalyani R Patel, Jennifer Pogoriler, Elise C Whalen, Kathryn A Wikenheiser-Brokamp, Natalie M Villafranco, Rachel K Hopper, J Usha Raj, Steven H Abman, Pediatric Pulmonary Hypertension Network (Pphnet)

Faculty, Staff and Students Publications

It is increasingly recognised that diverse genetic respiratory disorders present as severe pulmonary hypertension (PH) in the neonate and young infant, but many controversies and uncertainties persist regarding optimal strategies for diagnosis and management to maximise long-term outcomes. To better define the nature of PH in the setting of developmental lung disease (DEVLD), in addition to the common diagnoses of bronchopulmonary dysplasia and congenital diaphragmatic hernia, we established a multidisciplinary group of expert clinicians from stakeholder paediatric specialties to highlight current challenges and recommendations for clinical approaches, as well as counselling and support of families. In this review, we characterise …

Facilitators And Barriers To Initiating And Completing Tuberculosis Preventive Treatment Among Children And Adolescents Living With Hiv In Uganda: A Qualitative Study Of Adolescents, Caretakers And Health Workers, Pauline Mary Amuge, Denis Ndekezi, Moses Mugerwa, Dickson Bbuye, Diana Antonia Rutebarika, Lubega Kizza, Christine Namugwanya, Angella Baita, Peter James Elyanu, Patricia Nahirya Ntege, Dithan Kiragga, Carol Birungi, Adeodata Rukyalekere Kekitiinwa, Agnes Kiragga, Moorine Peninah Sekadde, Nicole-Austin Salazar, Anna Maria Mandalakas, Philippa Musoke

Faculty, Staff and Students Publications

INTRODUCTION: People living with HIV (PLHIV) have a 20-fold risk of tuberculosis (TB) disease compared to HIV-negative people. In 2021, the uptake of TB preventive treatment among the children and adolescents living with HIV at the Baylor-Uganda HIV clinic was 45%, which was below the national target of 90%. Minimal evidence documents the enablers and barriers to TB preventive treatment (TPT) initiation and completion among children and adolescents living with HIV(CALHIV). We explored the facilitators and barriers to TPT initiation and completion among CALHIV among adolescents aged 10-19years and caretakers of children below 18years.

METHODS: We conducted a qualitative study …

The Impact Of Bariatric Surgery On Glutathione Synthesis In Individuals With Severe Obesity, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

Glycine is deficient in individuals with obesity but improves following bariatric surgery. Glycine deficiency could impair glutathione (GSH) synthesis and worsen oxidative stress. We examined the impact of obesity-associated glycine deficiency and bariatric surgery on GSH synthesis. Twenty-one participants with severe obesity and twenty-one healthy weight controls were recruited. [1,2-13C2] glycine was infused to measure the erythrocyte (RBC) GSH synthesis rate. Participants with obesity underwent bariatric surgery, and 19 were restudied six months post-surgery. Compared to healthy weight controls, individuals with obesity had significantly lower concentrations of RBC GSH (2.43 ± 0.23 vs. 2.63 ± 0.26 mmol/L, p < 0.01). However, there were no differences in GSH fractional synthesis rate [78.0 (51.4–123.7) vs. 76.9 (49.3–110.1) % pool/day, p = …

Novel Il-4/Hb-Egf-Dependent Crosstalk Between Eosinophils And Macrophages Controls Liver Regeneration After Ischaemia And Reperfusion Injury, Yang Yang, Long Xu, Constance Atkins, Lily Kuhlman, Jie Zhao, Jong-Min Jeong, Yankai Wen, Nicolas Moreno, Kang Ho Kim, Yu A An, Fenfen Wang, Steve Bynon, Vincenzo Villani, Bin Gao, Frank Brombacher, Raymond Harris, Holger K Eltzschig, Elizabeth Jacobsen, Cynthia Ju

Faculty, Staff and Student Publications

OBJECTIVE: Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair.

DESIGN: Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury. Aside from exogenous cytokine or neutralising antibody treatments, mechanistic studies made use of a panel of mouse models of eosinophil-specific IL-4/IL-13-deletion, cell-specific IL-4rα-deletion in liver macrophages and hepatocytes and macrophage-specific deletion of heparin-binding …

In Utero Exposure To Antihistamines And Risk Of Hepatocellular Carcinoma In A Multigenerational Cohort, Caitlin C Murphy, Karim Seif El Dahan, Amit G Singal, Piera M Cirillo, Nickilou Y Krigbaum, Barbara A Cohn

Faculty, Staff and Student Publications

BACKGROUND: Growing evidence suggests that liver disease originates in early life. Antihistamines cross the placenta and are frequently prescribed to pregnant women to treat nausea and vomiting, as well as allergy and asthma symptoms. Exposure to antihistamines in utero may impact the developing liver by reprogramming or inducing epigenetic changes in fetal hepatocytes.

METHODS: We examined in utero exposure to antihistamines and the risk of HCC in the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in the East Bay, CA, between 1959 and 1966 (n=14,507 mothers and 18,751 liveborn offspring). We reviewed mothers' medical records …

Low Vitamin D Levels In Patients With Symptoms Of Gastroparesis: Relationships With Nausea And Vomiting, Gastric Emptying And Gastric Myoelectrical Activity, Kenneth L Koch, Henry P Parkman, Katherine P Yates, Mark L Van Natta, Madhusudan Grover, Gianrico Farrugia, Thomas L Abell, Richard W Mccallum, Irene Sarosiek, Braden Kuo, Robert J Shulman, Laura Miriel, James Tonascia, Pankaj J Pasricha

Faculty, Staff and Students Publications

Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied.

AIMS: To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp.

METHODS: 25-hydroxy-vitamin D was measured in patients at enrollment in the Gastroparesis Clinical Consortium Registry. Gastroparesis Cardinal Symptoms Index (GCSI), gastric emptying, and GMA before and after water load satiety test (WLST) were measured. GMA, expressed as percentage distribution of activity in normal and …

Global Prevalence Of Metabolic Dysfunction-Associated Fatty Liver Disease-Related Hepatocellular Carcinoma: A Systematic Review And Meta-Analysis, Harry Crane, Guy D Eslick, Cameron Gofton, Anjiya Shaikh, George Cholankeril, Mark Cheah, Jian-Hong Zhong, Gianluca Svegliati-Baroni, Alessandro Vitale, Beom Kyung Kim, Sang Hoon Ahn, Mi Na Kim, Simone I Strasser, Jacob George

Faculty, Staff and Students Publications

BACKGROUND/AIMS: The global proportion of hepatocellular carcinoma (HCC) attributable to metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. The MAFLD diagnostic criteria allows objective diagnosis in the presence of steatosis plus defined markers of metabolic dysfunction, irrespective of concurrent liver disease. We aimed to determine the total global prevalence of MAFLD in HCC cohorts (total-MAFLD), including the proportion with MAFLD as their sole liver disease (single-MAFLD), and the proportion of those with concurrent liver disease where MAFLD was a contributary factor (mixed-MAFLD).

METHODS: This systematic review and meta-analysis included studies systematically ascertaining MAFLD in HCC cohorts, defined using international expert …

Optimization Of Kidney Health In Liver Transplant Candidates: Pretransplant Considerations And Modalities, Muhammad Y Jan, Kavish R Patidar, Marwan S Ghabril, Chandrashekhar A Kubal

Faculty, Staff and Students Publications

Patients with decompensated end-stage liver disease (ESLD) are at increased risk for mortality, and only liver transplantation (LT) offers meaningful hope for survival. These patients are at risk for kidney dysfunction through the continuum of care for ESLD including LT. We discuss the role of accurate estimation and measurement of baseline glomerular filtration rate in assessment of kidney dysfunction among those with ESLD. Optimizing kidney function is a vital goal in the management of these patients before LT. In this review, we summarize salient aspects of assessing and optimizing kidney function in this patient population. Precipitating factors and different causes …

Bile Acids Differentially Regulate Longitudinal Smooth Muscle Contractility In Everted Mouse Ileum, Peace N Dike, Krishnakant G Soni, Diana S Chang, Geoffrey A Preidis

Faculty, Staff and Students Publications

Bile acids regulate gastrointestinal motility by mechanisms that are poorly understood. Standard isolated tissue bath assays might not recapitulate in vivo physiology if contractile responses to certain bile acids require direct application to the intestinal mucosa. We sought to determine the feasibility of quantifying longitudinal smooth muscle contractile responses to bile acids from intact segments of everted mouse ileum. Ileum from adult female C57BL/6J mice was isolated, gently everted over a notched metal rod, and mounted in tissue baths. Individual bile acids and agonists of bile acid receptors were added to the baths, and longitudinal smooth muscle contractile responses were …

An Electronic Health Record Model For Predicting Risk Of Hepatic Fibrosis In Primary Care Patients, Aaron P Thrift, Theresa H Nguyen Wenker, Kyler Godwin, Maya Balakrishnan, Hao T Duong, Rohit Loomba, Fasiha Kanwal, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND: One challenge for primary care providers caring for patients with nonalcoholic fatty liver disease is to identify those at the highest risk for clinically significant liver disease.

AIM: To derive a risk stratification tool using variables from structured electronic health record (EHR) data for use in populations which are disproportionately affected with obesity and diabetes.

METHODS: We used data from 344 participants who underwent Fibroscan examination to measure liver fat and liver stiffness measurement [LSM]. Using two approaches, multivariable logistic regression and random forest classification, we assessed risk factors for any hepatic fibrosis (LSM > 7 kPa) and significant hepatic …

Controversies In Terlipressin And Transplantation In The United States: How Do We Meld The Two?, Eric M Przybyszewski, Robert M Wilechansky, Paige Mclean Diaz, Andrew S Allegretti, Lisa B Vanwagner, Giuseppe Cullaro, Josh Levitsky, Pere Ginès, Salvatore Piano, Sumeet K Asrani, Kavish R Patidar, Hrs-Harmony Consortium

Faculty, Staff and Students Publications

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a severe complication of cirrhosis that carries a poor prognosis. The recent Food and Drug Administration approval of terlipressin has substantial implications for managing HRS-AKI and liver allocation in the United States. Terlipressin has been available in Europe for over a decade, and several countries have adapted policy changes such as Model for End-Stage Liver Disease (MELD) score "lock" for HRS-AKI. In this article, we outline the European experience with terlipressin use and explore the question of whether terlipressin treatment for HRS-AKI should qualify for the MELD score "lock" in the United States in …

Severe Febrile Neutropenia And Pancytopenia In A Patient With Advanced Hepatocellular Carcinoma Treated With Atezolizumab And Bevacizumab: A Case Report, Shadi Chamseddine, Michael Lapelusa, Kristen Carter, Van Nguyen, Yehia I Mohamed, Yara Sakr, Cristhiam M Rojas-Hernandez, Rikita I Hatia, Manal Hassan, John A Goss, Khaled M Elsayes, Asif Rashid, Ryan Sun, Hop Sanderson Tran Cao, Hesham M Amin, Ahmed O Kaseb

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs), agents that stimulate T-cell function, have become the standard first-line treatment for unresectable hepatocellular carcinoma (HCC). However, they may also cause immune-related adverse events (irAEs), which are rare and have not been extensively reported. Here, we describe a case of severe febrile neutropenia and pancytopenia after atezolizumab plus bevacizumab (atezo/bev) therapy and its treatment course.

CASE DESCRIPTION: The combination of atezo/bev was initiated as the first-line treatment for a man in his early 50s, who was diagnosed with unresectable HCC. The first treatment cycle was administered in the outpatient setting, and the patient developed a …

In-Silico Analysis Of Tmem2 As A Pancreatic Adenocarcinoma And Cancer-Associated Fibroblast Biomarker, And Functional Characterization Of Nsc777201, For Targeted Drug Development, Prateeti Srivastava, Vijesh Kumar Yadav, Tzu-Hao Chang, Emily Chia-Yu Su, Bashir Lawal, Alexander Th Wu, Hsu-Shan Huang

Faculty, Staff and Student Publications

Pancreatic adenocarcinoma (PAAD), known as one of the deadliest cancers, is characterized by a complex tumor microenvironment, primarily comprised of cancer-associated fibroblasts (CAFs) in the extracellular matrix. These CAFs significantly alter the matrix by interacting with hyaluronic acid (HA) and the enzyme hyaluronidase, which degrades HA - an essential process for cancer progression and spread. Despite the critical role of this interaction, the specific functions of CAFs and hyaluronidase in PAAD development are not fully understood. Our study investigates this interaction and assesses NSC777201, a new anti-cancer compound targeting hyaluronidase. This research utilized computational methods to analyze gene expression data …

Association Of Tea And Coffee Consumption And Biliary Tract Cancer Risk: The Biliary Tract Cancers Pooling Project, Yu-Han Huang, Erikka Loftfield, Ilona Argirion, Hans-Olov Adami, Demetrius Albanes, Andrew T Chan, Veronika Fedirko, Gary E Fraser, Neal D Freedman, Graham G Giles, Patricia Hartge, Verena Katzke, Synnove F Knutsen, James Lacey, Linda M Liao, Juhua Luo, Roger L Milne, Katie M O'Brien, Ulrike Peters, Jenny N Poynter, Mark P Purdue, Kim Robien, Sven Sandin, Dale P Sandler, Veronica W Setiawan, Jae H Kang, Tracey G Simon, Rashmi Sinha, Trang Vopham, Stephanie J Weinstein, Emily White, Xuehong Zhang, Bin Zhu, Katherine A Mcglynn, Peter T Campbell, Mei-Hsuan Lee, Jill Koshiol

Faculty, Staff and Student Publications

Background and aims: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence.

Approach and results: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and < 3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR< 3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers.

Conclusions: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.

Predicting Mortality Within 1 Year Of Art Initiation In Children And Adolescents Living With Hiv In Sub-Saharan Africa: A Retrospective Observational Cohort Study, Alexander Kay, Bhekumusa Lukhele, Sandile Dlamini, Abigail Seeger, Phumzile Dlamini, Sandile Ndabezitha, Nobuhle Mthethwa, Teresa Steffy, Lilian Komba, Pauline Amuge, Eunice Ketangenyi, Peter Elyanu, Adamson Munthali, Amos Msekandiana, Yvonne Maldonado, Elizabeth Chiao, Adeodata Kekitiinwa, Lineo Thahane, Lumumba Mwita, H Lester Kirchner, Anna Maria Mandalakas

Faculty, Staff and Students Publications

BACKGROUND: Differentiated service delivery (DSD) for children and adolescents living with HIV can improve targeted resource use. We derived a mortality prediction score to guide clinical decision making for children and adolescents living with HIV.

METHODS: Data for this retrospective observational cohort study were evaluated for all children and adolescents living with HIV and initiating antiretroviral therapy (ART); aged 0-19 years; and enrolled at Baylor clinics in Eswatini, Malawi, Lesotho, Tanzania, and Uganda between 2005 and 2020. Data for clinical prediction, including anthropometric values, physical examination, ART, WHO stage, and laboratory tests were captured at ART initiation. Backward stepwise variable …

Systemic Inflammatory Markers Of Persistent Cerebral Edema After Aneurysmal Subarachnoid Hemorrhage, Nadia Khan, Magdalena Kurnik-Łucka, Gniewomir Latacz, Krzysztof Gil

Faculty, Staff and Student Publications

In the first part of this article, the role of intestinal epithelial tight junctions (TJs), together with gastrointestinal dopaminergic and renin-angiotensin systems, are narratively reviewed to provide sufficient background. In the second part, the current experimental data on the interplay between gastrointestinal (GI) dopaminergic and renin-angiotensin systems in the regulation of intestinal epithelial permeability are reviewed in a systematic manner using the PRISMA methodology. Experimental data confirmed the copresence of DOPA decarboxylase (DDC) and angiotensin converting enzyme 2 (ACE2) in human and rodent enterocytes. The intestinal barrier structure and integrity can be altered by angiotensin (1-7) and dopamine (DA). Both …

Transcriptomic Signature, Bioactivity And Safety Of A Non-Hepatotoxic Analgesic Generating Am404 In The Midbrain Pag Region, Hernan A. Bazan, Surjyadipta Bhattacharjee, Madigan M. Reid, Bokkyoo Jun, Connor Polk, Madeleine Strain, Linsey A. St Pierre, Neehar Desai, Patrick W. Daly, Jessica A. Cucinello-Ragland, Scott Edwards, Javier Recio, Julio Alvarez-Builla, James J. Cai, Nicolas G. Bazan

School of Medicine Faculty Publications

Safe and effective pain management is a critical healthcare and societal need. The potential for acute liver injury from paracetamol (ApAP) overdose; nephrotoxicity and gastrointestinal damage from chronic non-steroidal anti-inflammatory drug (NSAID) use; and opioids’ addiction are unresolved challenges. We developed SRP-001, a non-opioid and non-hepatotoxic small molecule that, unlike ApAP, does not produce the hepatotoxic metabolite N-acetyl-p-benzoquinone-imine (NAPQI) and preserves hepatic tight junction integrity at high doses. CD-1 mice exposed to SRP-001 showed no mortality, unlike a 70% mortality observed with increasing equimolar doses of ApAP within 72 h. SRP-001 and ApAP have comparable antinociceptive effects, including the complete …

Parallel Use Of Low-Complexity Automated Nucleic Acid Amplification Tests On Respiratory Samples And Stool With Or Without Lateral Flow Lipoarabinomannan Assays To Detect Pulmonary Tuberculosis Disease In Children, Laura Olbrich, Alexander W Kay, Stephanie Bjerrum, Bada Yang, Johanna Åhsberg, Ruvandhi R Nathavitharana, Andreas Lundh, Maunank Shah, Devan Jaganath

Faculty, Staff and Students Publications

This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To compare the diagnostic accuracy of the parallel use of low-complexity automated nucleic acid amplification tests on respiratory and stool specimens in children and lateral flow urine lipoarabinomannan amongst children with HIV versus each assay alone for detecting pulmonary tuberculosis. Secondary objectives To compare the diagnostic accuracy of low-complexity automated nucleic acid amplification tests on respiratory and stool specimens in combination versus each sample type alone. To investigate the following sources of heterogeneity: clinical setting, signs and symptoms of pulmonary tuberculosis disease, screening positivity by chest …