tbuckley/cabot-search huggingface dataset:
The rise of multidisciplinary clinics in hepatology: A practical, how-to-guide, and review of the literature
Authors: Nicholas Lim, Deepika Devuni, Margarita German, Jennifer Guy, Atoosa Rabiee, Pratima Sharma, Alexandra Shingina, Hersh Shroff, Anjana Pillai
Journal: Hepatology (2024)

Multidisciplinary clinics (MDCs) are gaining momentum throughout the medical field, having initially been pioneered in oncology clinics due to their inherent ability to streamline complex care and improve both patient outcomes and the patient care experience. Liver transplant and hepatobiliary tumor clinics are examples of established MDCs in hepatology. With the changing landscape of liver disease in regard to etiology and patient complexity and acuity, there is a clear need for efficient, highly coordinated care. These changes highlight opportunities for hepatology MDCs in alcohol-associated liver disease, metabolic dysfunction-associated steatotic liver disease, and palliative care. This review provides practical advice in navigating the complex logistics of establishing and maintaining a hepatology MDC while also reviewing the emerging evidence on clinical outcomes for patients seen in these MDCs. As hepatology looks to the future, establishment of MDCs in key clinical areas will be the cornerstone of patient care.
To the Editor: Don’t forget to discuss TIPS in patients surviving an episode of alcoholic hepatitis
Authors: Marika Rudler, Charlotte Bouzbib, Dominique Thabut
Journal: Hepatology (2024)

To the editor, We read with great interest the study by Gratacós-Ginès et al,1 suggesting that recurrent alcohol-associated hepatitis (AH) is common and associated with increased mortality when compared with the index episode of alcoholic hepatitis. Data were lacking regarding recurrent AH, and this elegant study is most than welcome. However, we would like to underline some aspects that should be kept in mind when reading the article. First, important data, such as the number of patients with definite, ie, histologically proven AH, are missing. Indeed, a recent study underlined the suboptimal accuracy of noninvasive methods to diagnose AH,2 which may conduct the reader to hypothesize that patients with other causes of acute decompensation may have been included. Moreover, several years ago, we showed that patients with a typical presentation of severe AH had a definite AH in only 80% of cases in case of bleeding (90 patients in the current study).3 Second, it would also have been interesting to provide data on treatments that could have changed the global prognosis of the patients who recovered after the first AH, such as nonselective beta-blockers or TIPS. One can hypothesize that patients with AH and concomitant acute variceal bleeding (n=76) would have been candidates for preemptive TIPS placement. Indeed, the median Child-Pugh score was 10 during the first AH episode, and preemptive TIPS is currently indicated in patients with Child-Pugh C 10–13 cirrhosis.4 Last, the authors found that 51% of patients who were abstinent after first AH did not develop recurrent AH. We do believe that this result should be cautiously interpreted, especially because of the retrospective design of the study: one can hypothesize that patients with significant liver-related events were referred more often, those more prone to be nonabstinent. In conclusion, we agree with the authors' statement that patients surviving an episode of AH should undergo intense alcohol use disorder therapy. We also do believe that optimal medical management, including liver biopsies, nonselective beta-blockers, or TIPS when indicated, are mandatory.
Mdka produced by the activated HSCs drives bipotential progenitor cell redifferentiation during zebrafish biliary-mediated liver regeneration
Authors: Xintao Zhang, Huijuan Liu, Pengcheng Cai, Zhuofu Huang, Jianlong Ma, Lingfei Luo
Journal: Hepatology (2024)

After extensive hepatocyte loss or impaired hepatocyte proliferation, liver regeneration occurs through trans-differentiation of biliary epithelial cells (BECs), which involves dedifferentiation of biliary epithelial cells into bipotential progenitor cells (BP-PCs) and subsequent redifferentiation of BP-PCs into nascent hepatocytes and biliary epithelial cells. Despite several studies on the redifferentiation process of BP-PCs into nascent hepatocytes, the contributions of nonparenchymal cells in this process remain poorly understood.
The past, present, and the future of disc nucleus replacement. A systematic review of a large diversity of ideas and experiences
Authors: Hans-Joachim Wilke, Vincenza Sciortino
Journal: Biomaterials (2024)

Disc nucleus replacement (NR) is a challenging surgical technique used as a medical treatment for early-stage disc herniation to restore disc height and the biomechanical function of a motion segment, which may reduce low back pain. The surgical procedure involves the removal and replacement of the degenerated nucleus pulposus with a substitute by accessing the annulus fibrosos via a created hole. Over the decades, nucleus replacement has been an important issue, leading to the development of different substitute alternatives. The first ideas are dated to the 1950s and since then, more than a hundred nucleus replacement concepts can be identified. There were numerous attempts and several clinical trials; however, after more than 70 years of research, no gold standard for nucleus pulposus replacement has been identified. This review aims to collect the different nucleus replacements reported in the literature, thus understanding what failed, what could be improved and what are the opportunities for the future. A systematic review of the literature was performed using a keyword-based search on PubMed, Web of Science, and Scopus databases to detect all nucleus replacements presented in the past by clinicians and engineers. Several studies were extracted from which the main nucleus replacements over the years were investigated, including the ones that received CE mark, FDA approval, or IDE approval and, also those involved in clinical trials. A total of 116 studies were included in this review. The extracted data concern the nucleus replacements proposed over the years to create a historical background as complete as possible, including their mechanical and biomechanical characterization and the clinical trials conducted over the years. Nucleus disc arthroplasty has been explored for many years. Unfortunately, even today there is still nothing safe and definitive in this surgical practice. This review provides an overview of the nucleus replacement history. A breakthrough could be the improvements in technologies for the annulus fibrous closing or sealing and the tissue engineering and medical regenerative techniques which could certainly ensure a higher NR implantation success rate in the future of this clinical treatment. It is not yet clear what is the future of this clinical practice. Only scientific research can answer the question: is the nucleus replacement still a possible clinical solution?
The Legacy Effect of Intensive versus Standard BP Control on the Incidence of Needing Dialysis or Kidney Transplantation
Authors: Nicholas M. Pajewski, Srinivasan Beddhu, Adam P. Bress, Tara I. Chang, Glenn M. Chertow, Alfred K. Cheung, William C. Cushman, Barry I. Freedman, Tom Greene, Karen C. Johnson, Byron C. Jaeger, Manjula Kurella Tamura, Cora E. Lewis, Mahboob Rahman, David M. Reboussin, Michael V. Rocco, Jeff D. Williamson, Paul K. Whelton, Jackson T. Wright, Paul E. Drawz, Joachim H. Ix
Journal: Journal of the American Society of Nephrology (2024)

Key Points In the Systolic Blood Pressure Intervention Trial (SPRINT), the longer-term incidence of needing dialysis or transplantation was low and primarily associated with baseline kidney function. Rates of dialysis or transplantation were higher with intensive versus standard treatment, though the differences were not statistically significant. Background The Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive lowering of systolic BP increased the risk of incident CKD and episodes of AKI. Whether intensive treatment changes the risk of kidney failure is unknown. The goal of this study was to estimate the legacy effect of intensive versus standard systolic BP lowering on the longer-term incidence of kidney failure. Methods This study is a secondary analysis of a randomized, open-label clinical trial with observational follow-up. Between 2010 and 2013, patients 50 years and older with hypertension and higher cardiovascular risk excluding those with diabetes mellitus, history of stroke, proteinuria &gt;1 g/d, or polycystic kidney disease were recruited from 102 clinic sites in the United States and Puerto Rico. Participants were randomized to a systolic BP goal of &lt;120 mm Hg (intensive treatment) or &lt;140 mm Hg (standard treatment group). We linked participants with the United States Renal Data System to ascertain kidney failure (initiation of dialysis therapy or transplantation) and the US National Death Index to ascertain all-cause mortality through 2020. Results Based on analysis of 9279 (99.1%) of 9361 randomized participants, 101 cases of kidney failure occurred over a median follow-up of 8.6 years (interquartile range, 8.0–9.1 years), with the majority occurring in 74 (73.3%) participants with an eGFR &lt;45 ml/min per 1.73 m 2 at baseline. Intensive treatment did not significantly increase the risk of kidney failure either overall (cause-specific hazard ratio, 1.20; 95% confidence interval, 0.81 to 1.78) or in the subgroup of participants with baseline eGFR &lt;45 ml/min per 1.73 m 2 (cause-specific hazard ratio, 1.43; 95% confidence interval, 0.89 to 2.30). Conclusions Overall, and in patients with eGFR &lt;45 ml/min per 1.73 m 2 , there were higher rates of dialysis or transplantation among SPRINT participants randomized to intensive treatment, but the modest differences observed were not statistically significant. Clinical Trial registry name and registration number: SPRINT, NCT01206062.
Photothermal switch by gallic acid-calcium grafts synthesized by coordination chemistry for sequential treatment of bone tumor and regeneration
Authors: Xiaodong Hou, Lei Zhang, Yixing Chen, Zhiqing Liu, Xinyu Zhao, Bingqiang Lu, Yiping Luo, Xinyu Qu, Olga Musskaya, Ilya Glazov, Anatoly I. Kulak, Feng Chen, Jing Zhao, Zifei Zhou, Longpo Zheng
Journal: Biomaterials (2024)

The residual bone tumor and defects which is caused by surgical therapy of bone tumor is a major and important problem in clinicals. And the sequential treatment for irradiating residual tumor and repairing bone defects has wildly prospects. In this study, we developed a general modification strategy by gallic acid (GA)-assisted coordination chemistry to prepare black calcium-based materials, which combines the sequential photothermal therapy of bone tumor and bone defects. The GA modification endows the materials remarkable photothermal properties. Under the near-infrared (NIR) irradiation with different power densities, the black GA-modified bone matrix (GBM) did not merely display an excellent performance in eliminating bone tumor with high temperature, but showed a facile effect of the mild-heat stimulation to accelerate bone regeneration. GBM can efficiently regulate the microenvironments of bone regeneration in a spatial-temporal manner, including inflammation/immune response, vascularization and osteogenic differentiation. Meanwhile, the integrin/PI3K/Akt signaling pathway of bone marrow mesenchymal stem cells (BMSCs) was revealed to be involved in the effect of osteogenesis induced by the mild-heat stimulation. The outcome of this study not only provides a serial of new multifunctional biomaterials, but also demonstrates a general strategy for designing novel blacked calcium-based biomaterials with great potential for clinical use.
Cervical Cancer Evades the Host Immune System through the Inhibition of Type I Interferon and CXCL9 by LIF
Authors: Ester Bonfill-Teixidor, Almudena Neva-Alejo, Alexandra Arias, Isabel Cuartas, Raffaella Iurlaro, Ester Planas-Rigol, Laura Solé, Irene Pecharromán, Silvia Cabrera, Ángel García, David Garcia-Illescas, Lluís Espinosa, Antonio Gil-Moreno, Ana Oaknin, Joan Seoane
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Cervical cancer is a viral-associated tumor caused by the infection with the human papilloma virus. Cervical cancer is an immunogenic cancer that expresses viral antigens. Despite being immunogenic, cervical cancer does not fully respond to immune checkpoint inhibitors (ICI). LIF is a crucial cytokine in embryo implantation, involved in maternal tolerance that acts as an immunomodulatory factor in cancer. LIF is expressed in cervical cancer and high levels of LIF is associated with poor prognosis in cervical cancer. Experimental Design: We evaluated the impact of LIF on the immune response to ICI using primary plasmocytoid dendritic cells (pDC) and macrophage cultures, syngeneic animals and patient-derived models that recapitulate the human tumor microenvironment. Results: We found that the viral proteins E6 and E7 induce the expression of LIF via the NFκB pathway. The secreted LIF can then repress type I interferon expressed in pDCs and CXCL9 expressed in tumor-associated macrophages. Blockade of LIF promotes the induction of type I interferon and CXCL9 inducing the tumor infiltration of CD8 T cells. This results in the sensitization of the tumor to ICI. Importantly, we observed that patients with cervical cancer expressing high levels of LIF tend to be resistant to ICI. Conclusions: Our data show that the HPV virus induces the expression of LIF to provide a selective advantage to the tumor cell by generating local immunosuppression via the repression of type I interferon and CXCL9. Combinatory treatment with blocking antibodies against LIF and ICI could be effective against cervical cancer expressing high levels of LIF.
Clinical value of liquid biopsy in FGFR2 fusion-positive cholangiocarcinoma patients during targeted therapy
Authors: Alberto Gonzalez-Medina, Maria Vila-Casadesús, Marina Gomez-Rey, Carles Fabregat-Franco, Alexandre Sierra, Tian V. Tian, Florian Castet, Gloria Castillo, Judit Matito, Paola Martinez, Josep M. Miquel, Paolo Nuciforo, Raquel Pérez-López, Teresa Macarulla, Ana Vivancos
Journal: Clinical Cancer Research (2024)

Abstract Purpose: FGFR2 fusions occur in 10% to 15% of patients with intrahepatic cholangiocarcinoma (iCCA), potentially benefiting from FGFR inhibitors (FGFRi). We aimed to assess the feasibility of detecting FGFR2 fusions in plasma and explore plasma biomarkers for managing FGFRi treatment. Experimental Design: We conducted a retrospective study in 18 patients with iCCA and known FGFR2 fusions previously identified in tissue samples from prior FGFRi treatment. Both tissue and synchronous plasma samples were analyzed using a custom hybrid capture gene panel with next-generation sequencing (VHIO-iCCA panel) and validated against commercial vendor results. Longitudinal plasma analysis during FGFRi was performed. Subsequently, we explored the correlation between plasma biomarkers, liver enzymes, tumor volume, and clinical outcomes. Results: Sixteen patients (88.9%) were positive for FGFR2 fusion events in plasma. Remarkably, the analysis of plasma suggests that lower levels of ctDNA are linked to clinical benefits from targeted therapy and result in improved progression-free survival and overall survival. Higher concentrations of cell-free DNA before FGFRi treatment were linked to worse overall survival, correlating with impaired liver function and indicating compromised cell-free DNA removal by the liver. Additionally, increased ctDNA or the emergence of resistance mutations allowed earlier detection of disease progression compared with standard radiologic imaging methods. Conclusions: VHIO-iCCA demonstrated accurate detection of FGFR2 fusions in plasma. The integration of information from various plasma biomarkers holds the potential to predict clinical outcomes and identify treatment failure prior to radiologic progression, offering valuable guidance for the clinical management of patients with iCCA.
Effectiveness of PARP inhibitor maintenance therapy in ovarian cancer by BRCA1/2 and a scar-based HRD signature in real-world practice
Authors: Debra L. Richardson, Julia C. F. Quintanilha, Natalie Danziger, Gerald Li, Ethan Sokol, Alexa B. Schrock, Ericka Ebot, Neeru Bhardwaj, Tanesha Norris, Anosheh Afghani, Anthony Frachioni, Christina Washington, Lauren Dockery, Julia Elvin, Ryon P. Graf, Kathleen N. Moore
Journal: Clinical Cancer Research (2024)

The purpose of the study was to compare the effectiveness of PARP inhibitor maintenance therapy (mPARPi) in real-world practice by biomarker status [BRCA1/2 alterations (BRCAalt) and a homologous recombination deficiency signature (HRDsig)] in advanced ovarian cancer.
Development and Validation of a Noninvasive Model for the Detection of High-Risk Varices in Patients with Unresectable HCC
Authors: Neehar D Parikh, Patricia Jones, Reena Salgia, Irun Bhan, Lauren T Grinspan, Janice H Jou, Kali Zhou, Prasun Jalal, Giorgio Roccaro, Amol S Rangnekar, Jihane N Benhammou, Anjana Pillai, Neil Mehta, Joel Wedd, Ju Dong Yang, Amy K Kim, Andres Duarte-Rojo, Omobonike O Oloruntoba, Amit Tevar, Jennifer S Au, Yamile Blain, Sanjana Rao, Onofrio A Catalano, Sara Lewis, Mishal Mendiratta-Lala, Kevin King, Lekha Sachdev, Edward W Lee, Jill Bruno, Ihab Kamel, Celestina Tolosa, Karissa Kao, Tarek Badawi, Eric M Przybyszewski, Lisa Quirk, Piyush Nathani, Brandy Haydel, Emily Leven, Nicole Wong, Robert Albertian, Ariana Chen, Fuad Z Aloor, Islam B Mohamed, Ahmed Elkheshen, Charles Marvil, Gerard Issac, Joseph W Clinton, Stephanie M Woo, Jung Yum, Erin Rieger, Alan L Hutchison, Don A Turner, Manaf Alsudaney, Perla Hernandez, Ziyi Xu, Abdullah Khalid, Bethany Barrick, Bo Wang, Elliot B Tapper, Wei Hao, Amit G Singal
Journal: Clinical Gastroenterology and Hepatology (2024)
AbdomenAtlas: A large-scale, detailed-annotated, &amp; multi-center dataset for efficient transfer learning and open algorithmic benchmarking
Authors: Wenxuan Li, Chongyu Qu, Xiaoxi Chen, Pedro R A S Bassi, Yijia Shi, Yuxiang Lai, Qian Yu, Huimin Xue, Yixiong Chen, Xiaorui Lin, Yutong Tang, Yining Cao, Haoqi Han, Zheyuan Zhang, Jiawei Liu, Tiezheng Zhang, Yujiu Ma, Jincheng Wang, Guang Zhang, Alan Yuille, Zongwei Zhou
Journal: Medical Image Analysis (2024)
Genetic deletion of the kidney sodium/proton exchanger-3 (NHE3) does not alter calcium and phosphate balance due to compensatory responses
Authors: Søren B. Poulsen, Sathish K. Murali, Linto Thomas, Adrienne Assmus, Lena L. Rosenbæk, Rikke Nielsen, Henrik Dimke, Timo Rieg, Robert A. Fenton
Journal: Kidney International (2024)

The sodium/proton exchanger-3 (NHE3) plays a major role in acid–base and extracellular volume regulation and is also implicated in calcium homeostasis. As calcium and phosphate balances are closely linked, we hypothesized that there was a functional link between kidney NHE3 activity, calcium, and phosphate balance. Therefore, we examined calcium and phosphate homeostasis in kidney tubule-specific NHE3 knockout mice (NHE3loxloxPax8 mice). Compared to controls, these knockout mice were normocalcemic with no significant difference in urinary calcium excretion or parathyroid hormone levels. Thiazide-induced hypocalciuria was less pronounced in the knockout mice, in line with impaired proximal tubule calcium transport. Knockout mice had greater furosemide-induced calciuresis and distal tubule calcium transport pathways were enhanced. Despite lower levels of the sodium/phosphate cotransporters (NaPi)-2a and -2c, knockout mice had normal plasma phosphate, sodium-dependent 32Phosphate uptake in proximal tubule membrane vesicles and urinary phosphate excretion. Intestinal phosphate uptake was unchanged. Low dietary phosphate reduced parathyroid hormone levels and increased NaPi-2a and -2c abundances in both genotypes, but NaPi-2c levels remained lower in the knockout mice. Gene expression profiling suggested proximal tubule remodeling in the knockout mice. Acutely, indirect NHE3 inhibition using the SGLT2 inhibitor empagliflozin did not affect urinary calcium and phosphate excretion. No differences in femoral bone density or architecture were detectable in the knockout mice. Thus, a role for kidney NHE3 in calcium homeostasis can be unraveled by diuretics, but NHE3 deletion in the kidneys has no major effects on overall calcium and phosphate homeostasis due, at least in part, to compensating mechanisms.
Enhancing miR-19a/b induced cardiomyocyte proliferation in infarcted hearts by alleviating oxidant stress and controlling miR-19 release
Authors: Kai Wang, Jun Wen, Tian Liang, Haijun Hu, Shifen Li, Liyin Shen, Tanchen Ren, Yuejun Yao, Jieqi Xie, Jie Ding, Jinghai Chen, Yi-Da Tang, Yang Zhu, Changyou Gao
Journal: Biomaterials (2024)
Enhanced Anticancer Efficacy of TRAIL-Conjugated and Odanacatib-Loaded PLGA Nanoparticles in TRAIL resistant cancer
Authors: Thoa Thi Kim Nguyen, Seon Min Woo, Seung Un Seo, Asmita Banstola, Haesoo Kim, Ramesh Duwa, An Thi Thanh Vu, In-Sun Hong, Taeg Kyu Kwon, Simmyung Yook
Journal: Biomaterials (2024)
Chronic kidney disease leads to microglial potassium efflux and inflammasome activation in the brain
Authors: Silke Zimmermann, Akash Mathew, Olga Bondareva, Ahmed Elwakiel, Klarina Waldmann, Shihai Jiang, Rajiv Rana, Kunal Singh, Shrey Kohli, Khurrum Shahzad, Ronald Biemann, Thomas Roskoden, Silke Diana Storsberg, Christian Mawrin, Ute Krügel, Ingo Bechmann, Jürgen Goldschmidt, Bilal N. Sheikh, Berend Isermann
Journal: Kidney International (2024)

Cognitive impairment is common in extracerebral diseases such as chronic kidney disease (CKD). Kidney transplantation reverses cognitive impairment, indicating that cognitive impairment driven by CKD is therapeutically amendable. However, we lack mechanistic insights allowing development of targeted therapies. Using a combination of mouse models (including mice with neuron-specific IL-1R1 deficiency), single cell analyses (single nuclei RNA sequencing and single cell thallium autometallography), human samples and in vitro experiments we demonstrate that microglia activation impairs neuronal potassium homeostasis and cognition in CKD. CKD disrupts the barrier of brain endothelial cells in vitro and the blood-brain barrier in vivo, establishing that the uremic state modifies vascular permeability in the brain. Exposure to uremic conditions impairs calcium homeostasis in microglia, enhances microglial potassium efflux via the calcium-dependent channel KCa3.1, and induces p38-MAPK associated IL-1β maturation in microglia. Restoring potassium homeostasis in microglia using a KCa3.1-specific inhibitor (TRAM34) improves CKD-triggered cognitive impairment. Likewise, inhibition of the IL-1β receptor 1 (IL-R1) using anakinra or genetically abolishing neuronal IL-1R1 expression in neurons prevent CKD-mediated reduced neuronal potassium turnover and CKD-induced impaired cognition. Accordingly, in CKD mice, impaired cognition can be ameliorated by either preventing microglia activation or inhibiting IL-1R-signaling in neurons. Thus, our data suggest that potassium efflux from microglia triggers their activation, which promotes microglia IL-1β release and IL-1R1-mediated neuronal dysfunction in CKD. Hence, our study provides new mechanistic insight into cognitive impairment in association with CKD and identifies possible new therapeutic approaches.