tbuckley/cabot-search huggingface dataset:
Drug points: Leucopenia associated with lamotrigine
Authors: R J Nicholson, K P Kelly, I S Grant
Journal: BMJ (1995)

Ms R J NICHOLSON, Dr K P KELLY, and Dr I S GRANT (Western General Hospital, Edinburgh EH4 2XU) write: We report a case of septic shock secondary to leucopenia in a patient receiving lamotrigine for epilepsy.

A 35 year old woman who had been diagnosed as epileptic in December 1992 and was taking sodium valproate (400 mg three times daily) and propranolol (40 mg three times daily) for migraine was given lamotrigine in …
Continuous therapy in HHV-8 negative Multicentric Castleman Disease and prolonged progression-free survival
Authors: Yi Liu, Xuejiao Yin, Shengnan Ding, Jiaying Ge, Liya Ma, Min Yang, Xuxia Luo, Chengli Zhong, Sishi Fang, Qiumei Yao, Li Zhu, Wenjuan Yu, Liping Mao, Juying Wei, Xingnong Ye, De Zhou, Hongyan Tong, Haitao Meng, Jie Jin, Liangshun You
Journal: Journal of Hematology & Oncology (2024)

The optimal treatment endpoints and duration of continuous therapy for multicentric Castleman disease (MCD) remain controversial. We retrospectively analyzed data from 123 patients with Human Herpesvirus (HHV)-8 negative MCD. We demonstrated that continuous therapy significantly enhanced progression-free survival (PFS) in patients who achieved an optimal response after initial treatment. These findings underscore the critical role of continuous therapy in HHV-8 negative MCD. Further studies with larger cohorts are required to validate these findings.
Refractory gastrocutaneous fistula after gastrostomy removal successfully treated with submucosal dissection and endoscopic suture
Authors: Alice Burgevin, Elena De Cristofaro, Claire Michoud, Emilien Daire, Lauriane Deker, Jean-Christophe Saurin, Mathieu Pioche
Journal: Endoscopy (2024)

Placement of a gastrostomy tube is a basic procedure involving the creation of a gastrocutaneous fistula through which a tube or button device is placed. The tube can be removed when access is no longer required for patients who recover from their disease. The tract starts to close within the first day and usually closes within 3 days. However, a fistula may persist in 25% of cases [1]. Surgical closure has been widely replaced by endoscopic techniques. Various techniques have been described in small patient series: argon plasma coagulation, silver nitrate, biopsy with forceps, endoscopic submucosal dissection or electrocautery can be used for de-epithelization of the fistulous tract. Fibrin glue, clips [2], an over-the-scope clip [3], or bands can be used for closure. Nevertheless, simple means are not always effective and sometimes the combination of mucosal dissection with submucosal closure was described to be effective after failure of standard treatments [4].
Leveraging machine learning to enhance postoperative risk assessment in coronary artery bypass grafting patients with unprotected left main disease - A retrospective cohort study
Authors: Ahmed Elmahrouk, Amin Daoulah, Prashanth Panduranga, Rajesh Rajan, Ahmed Jamjoom, Omar Kanbr, Badr Alzahrani, Mohammed A. Qutub, Nooraldaem Yousif, Tarique Shahzad Chachar, Youssef Elmahrouk, Ali Alshehri, Taher Hassan, Wael Tawfik, Kamel Hazaa Haider, Abdulwali Abohasan, Adel N. Alqublan, Abdulrahman M. Alqahtani, Mohamed Ajaz Ghani, Faisal Omar M. Al Nasser, Wael Almahmeed, Ahmed A. Ghonim, Shahrukh Hashmani, Mohammed Alshehri, Abdelmaksoud Elganady, Abeer M. Shawky, Adnan Fathey Hussien, Seraj Abualnaja, Taha H. Noor, Ibrahim A. M. Abdulhabeeb, Levent Ozdemir, Wael Refaat, Hameedullah M. Kazim, Ehab Selim, Issam Altnji, Ahmed M. Ibrahim, Abdullah Alquaid, Amr A. Arafat
Journal: International Journal of Surgery (2024)

Risk stratification for patients undergoing coronary artery bypass surgery (CABG) for left main coronary artery (LMCA) disease is essential for informed decision-making. This study explored the potential of machine learning (ML) methods to identify key risk factors associated with mortality in this patient group.
Pickering emulsion-guided monomeric delivery of monophosphoryl lipid A for enhanced vaccination
Authors: Yiqun Du, Jiali Lv, Zongwei Hao, Zhaofeng Li, Tiantian Song, Huifang Ge, Hongyan Wang, Zhenyu Yu, Zhongwen Xie, Daxiang Li, Yuchen Liu
Journal: Journal of Controlled Release (2024)
The battle against paediatric HIV is far from over
Authors: Philippe Van de Perre, Thorkild Tylleskär
Journal: The Lancet (2024)

World AIDS Day 2023 was well marked by The Lancet with the publication of an excellent Seminar by Aaloke Mody and colleagues summarising the major achievements and the way forward in HIV epidemiology, prevention, treatment, and implementation strategies for public health.1Mody A Sohn AH Iwuji C Tan RKJ Venter F Geng EH HIV epidemiology, prevention, treatment, and implementation strategies for public health.Lancet. 2024; 403: 471-492Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar Unfortunately, not a single word was devoted to the prevention or treatment of paediatric HIV infection. Yet, over the past 15 years, none of the WHO targets for paediatric HIV elimination have been met, and more than 130 000 new paediatric infections occur each year.2UNAIDSThe path that ends AIDS: UNAIDS Global AIDS Update 2023. Joint United Nations Programme on HIV/AIDS, Geneva2023Crossref Google Scholar Elimination of paediatric HIV infection is currently out of reach, but new strategic options are available to reach it, particularly in settings with high HIV incidence.3Van de Perre P Goga A Ngandu N et al.Eliminating postnatal HIV transmission in high incidence areas: need for complementary biomedical interventions.Lancet. 2021; 397: 1316-1324Summary Full Text Full Text PDF PubMed Scopus (23) Google Scholar Paediatric HIV is massively under-diagnosed. Among children aged 1–14 years living with HIV in southern and eastern Africa, 39% are undiagnosed and therefore deprived of life-saving antiretroviral therapy (ART) and care.4Teasdale CA Zimba R Abrams EJ et al.Estimates of the prevalence of undiagnosed HIV among children living with HIV in Eswatini, Lesotho, Malawi, Namibia, Tanzania, Zambia, and Zimbabwe from 2015 to 2017: an analysis of data from the cross-sectional Population-based HIV Impact Assessment surveys.Lancet HIV. 2022; 9: e91-101Summary Full Text Full Text PDF PubMed Scopus (17) Google Scholar Triumphalism about the imminent elimination of paediatric HIV infection is based on the ever-increasing number of HIV-infected pregnant women who have started ART, one of the only progress indicators of the performance of prevention of mother-to-child transmission programmes that are monitored worldwide. However, impact indicators such as the number of infants and children born to HIV-infected mothers who are offered HIV diagnosis and eventually HIV treatment are almost universally ignored. The net effect of ignorance is complacency and disinterest on the part of the scientific community in the fight against paediatric HIV. For too long, the silent paediatric HIV epidemic has been made invisible and ignored. We declare no competing interests. HIV epidemiology, prevention, treatment, and implementation strategies for public health
Integrating patient and public involvement and engagement in translational medicine
Authors: Karen L Shaw, Melanie J Calvert, Persephone Borrow, Evelyn Chakera, Ronjon Chakraverty, Sarah E Hughes, Foram Khatsuria, Francesca A M Kinsella, Christel McMullan, Julie Richardson-Abraham, Vlada Yarosh, Olalekan Lee Aiyegbusi
Journal: The Lancet (2024)
Thoracic endovascular aortic repair with unibody single-branched stent-graft for type B aortic dissection: A real-world multicenter study
Authors: Xiaoye Li, Qing Zhou, Cunren Li, Zhengdong Wan, Hao Zhang, Nan Cai, Lei Zhang, Chao Song, Qingsheng Lu
Journal: International Journal of Surgery (2024)

Objective: To evaluate the outcome of TEVAR for TBAD and revascularization of LSA with Castor single-branched stent-graft. Summary Background Data: One-stage thoracic endovascular aortic repair (TEVAR) and revascularization of left subclavian artery (LSA) of type B aortic dissection (TBAD) with off-the-shelf stent-graft is limited. Methods: A multicenter study consisting of consecutive patients from 4 different centers in China treated with Castor single-branched stent-graft for TBAD was conducted. Rate of technical success, mortality, complications, and reinterventions were evaluated. Results: Between September 2018 and April 2022, 180 consecutive patients with TBAD received TEVAR with Castor single-branched stent-graft. Technical success was achieved in all patients. The mean oversize ratio at the proximal landing zone was 4.9±3.8% (median, 3.7; IQR, 2.0%-6.9%). Five patients died within the first 30 days after the operation or during hospitalization. Early reintervention was performed in 1 case. The median follow-up was 18.0 months (IQR, 13–24 months). Five patients died during follow-up, including three cases of respiratory failure, one case of immune thrombocytopenia purpura, and one case of cerebral hemorrhage. Three patients had reintervention. In total, 3 cases of stroke were recorded, which were all within 30 days after the operation. Image data at 1 year presented complete thrombosis in 97.1% cases for the false lumen covered by the stent-graft. Conclusions: TEVAR with Castor device for treatment of TBAD and revascularization of LSA is a feasible and safety technique. The deployment procedure is safe, easy, and accurate. Castor devices meets the hemodynamical and biomechanical requirement of elastic aorta and could restore the physiological blood flow pattern of LSA.
The role of artificial intelligence measured preoperative kidney volume in predicting kidney function loss in elderly kidney donors: A multicenter cohort study
Authors: Eun-Ah Jo, Juhan Lee, Seonggong Moon, Jin Sung Kim, Ahram Han, Jongwon Ha, Yong Chul Kim, Sangil Min
Journal: International Journal of Surgery (2024)

The increasing use of kidneys from elderly donors raises concerns due to age-related nephron loss. Combined with nephrectomy, this loss of nephrons markedly increases the risk of developing chronic kidney disease (CKD). This study aimed to investigate the prognostic value of preoperative kidney cortex volume in predicting the loss of kidney function in elderly donors, by developing an artificial intelligence (AI)-based model for precise kidney volume measurement and applying it to living kidney donors.
A natural adhesive-based nanomedicine initiates photothermal-directed in situ immunotherapy with durability and maintenance
Authors: Yunhong He, Hong Sun, Hanxiao Bao, Jue Hou, Qiaomei Zhou, Fan Wu, Xuanhao Wang, Mingli Sun, Junhui Shi, Guping Tang, Hongzhen Bai
Journal: Biomaterials (2024)
Predicting prognostic factors in kidney transplantation using a machine learning approach to enhance outcome predictions: a retrospective cohort study
Authors: Jin-Myung Kim, HyoJe Jung, Hye Eun Kwon, Youngmin Ko, Joo Hee Jung, Hyunwook Kwon, Young Hoon Kim, Tae Joon Jun, Sang-Hyun Hwang, Sung Shin
Journal: International Journal of Surgery (2024)

Accurate forecasting of clinical outcomes after kidney transplantation is essential for improving patient care and increasing the success rates of transplants. Our study employs advanced machine learning (ML) algorithms to identify crucial prognostic indicators for kidney transplantation. By analyzing complex datasets with ML models, we aim to enhance prediction accuracy and provide valuable insights to support clinical decision-making.
Simple severity scale for perforated peptic ulcer with generalized peritonitis: A derivation and internal validation study
Authors: Ryo Yamamoto, Shinya Hirakawa, Hisateru Tachimori, Tadashi Matsuoka, Hirotoshi Kikuchi, Hiroshi Hasegawa, Ken Shirabe, Yoshihiro Kakeji, Hirofumi Kawakubo, Yuko Kitagawa, Junichi Sasaki
Journal: International Journal of Surgery (2024)

Perforated peptic ulcer (PPU) causes peritonitis and requires surgery based on disease severity. This study aimed to develop and validate a severity scale for PPU with generalized peritonitis.
Complex causal association between immune cell phenotypes and bladder cancer: A mendelian randomization and mediation study
Authors: Changjiu Li, Chentao Lv, Jun Chen, Kun Shang, Huadong He, Chao Chen
Journal: International Journal of Surgery (2024)

Li, Changjiu; Lv, Chentao; Chen, Jun; Shang, Kun; He, Huadong; Chen, Chao Author Information
Adverse complications of cervical spinal fusion in patients with different types of diabetes mellitus: A retrospective nationwide inpatient sample database cross-sectional study
Authors: Yuan-Jing Liao, Lan-Wei Xu, Hao Xie, Qin-Feng Yang, Jian Wang, Lei Fan, Sheng-Lu Cao
Journal: International Journal of Surgery (2024)

Background: Diabetes mellitus (DM) is a prevalent chronic condition that influences spine surgery outcomes. The impact of type Ⅰ and type Ⅱ DM on adverse postoperative outcomes, mortality, prolonged length of stay (LOS), and increased in-hospital costs following cervical fusion surgery remains unclear in the past decade. This study aims to determine the specific effect of different classifications of DM on postoperative complications in patients experiencing cervical fusion surgery. Method: Data from the Nationwide Inpatient Sample database was acquired between 2010 and 2019. Patients experiencing cervical fusion were included and classified as having type I DM, type II DM, or neither. Patient demographics, hospital characteristics, operative variables, comorbidities, complications, and other postoperative outcomes were assessed. Propensity score matching analysis was used to balance baseline differences. Univariate and multivariate logistic regression were employed to determine the risk of postoperative outcomes in patients with different classifications of DM. Result: A total of 267,174 cervical spinal fusions were identified (224,255 were patients without DM, 670 patients had type I DM, and 42,249 patients had type II DM). After propensity score matching, the multivariate analysis of non-DM and type I DM patients shows significant difference in pneumonia ( P =0.020). However, type Ⅱ DM served as an independent predictor of an increased risk of acute cerebrovascular disease ( P =0.001), acute myocardial infarction ( P =0.014), pneumonia ( P =0.045), continuous trauma ventilation ( P =0.016), chest pain ( P &lt;0.001), urinary tract infection ( P &lt;0.001), transfusion ( P =0.005) and dysphagia ( P =0.013), prolonged LOS ( P &lt;0.001) and increased costs ( P =0.008). Conclusion: Using non-DM patients as a reference, type II DM group demonstrated a higher risk of postoperative complications than type I DM group among patients receiving cervical fusion surgery. This vital distinction could enhance risk stratification and guidance for patients diagnosed with DM before cervical fusion surgery.
Comparative performance of methylation DNA markers, brushing cytology, and FISH in diagnosing malignant biliary strictures
Authors: Jesus M. Banales, Ainhoa Lapitz, Luca Fabris
Journal: Hepatology (2024)

1Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute – Donostia University Hospital –, University of the Basque Country (UPV/EHU), Donostia-San Sebastian, Spain 2National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain 3IKERBASQUE, Basque Foundation for Science, Bilbao, Spain 4Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain 5Department of Medicine (DIMED), University of Padova, Padova, Italy 61st Clinical Medicine Unit, University-Hospital of Padova, Padova, Italy 7Department of Internal Medicine, Digestive Disease Section, Yale University, New Haven, CT, USA Abbreviations: CA19-9, carbohydrate antigen 19-9; CCA, cholangiocarcinoma; ddPCR, droplet digital Polymerase Chain Reaction; ERCP, endoscopic retrograde cholangiopancreatography; FISH, fluorescence in situ hybridization; MDM, methylated DNA markers; PDAC, pancreatic ductal adenocarcinoma; PSC, primary sclerosing cholangitis. Correspondence Jesus M. Banales, Biodonostia Research Institute (Donostia University, Hospital), IKEBASQUE (Basque Foundation for Science), University of Basque Country (UPV), San Sebastián, Spain., Department of Liver Diseases. Email: [email protected] Correspondence Luca Fabris, University of Padova, Department of Molecular Medicine, (DMM). Email: [email protected]
Letter to the editor: Bridging the gap between hepatitis C virus diagnosis and treatment to achieve elimination in the united states
Authors: Chrysovalantis Stafylis, Arjun P. Vij, Jeffrey D. Klausner
Journal: Hepatology (2024)

Keck School of Medicine, Department of Population and Public Health Sciences, University of Southern California Correspondence Jeffrey D. Klausner, 1845 N Soto St, Los Angeles, CA 90032. Email: [email protected]
PROTACs as Therapeutic Modalities for Drug Discovery in Castration-Resistant Prostate Cancer
Authors: Ling-Yu Wang, Chiu-Lien Hung, Tsan-Chun Wang, Hung-Chih Hsu, Hsing-Jien Kung, Kwang-Huei Lin
Journal: The Annual Review of Pharmacology and Toxicology (2024)

Castration-resistant prostate cancer (CRPC) presents significant challenges in clinical management due to its resistance to conventional androgen receptor (AR)-targeting therapies. The advent of proteolysis targeting chimeras (PROTACs) has revolutionized cancer therapy by enabling the targeted degradation of key molecular players implicated in CRPC progression. In this review we discuss the developments of PROTACs for CRPC treatment, focusing on AR and other CRPC-associated regulators. We provide an overview of the strategic trends in AR PROTAC development from the aspect of targeting site selection and preclinical antitumor evaluation, as well as updates on AR degraders in clinical applications. Additionally, we briefly address the current status of selective AR degrader development. Furthermore, we review new developments in PROTACs as potential CRPC treatment paradigms, highlighting those targeting chromatin modulators BRD4, EZH2, and SWI/SNF; transcription regulator SMAD3; and kinases CDK9 and PIM1. Given the molecular targets shared between CRPC and neuroendocrine prostate cancer (NEPC), we also discuss the potential of PROTACs in addressing NEPC.
Back to phosphodiesterase inhibitors for liver disease: are we ready for clinical trials?
Authors: Leila Gobejishvili, Craig J. McClain
Journal: Hepatology (2024)

1Department of Physiology, University of Louisville School of Medicine, Louisville, Kentucky 2Department of Medicine, University of Louisville School of Medicine, University of Louisville, Louisville, Kentucky 3Robley Rex VA Medical Center, Louisville, Kentucky, USA Correspondence Leila Gobejishvili, Department of Physiology, University of Louisville, 505 S. Hancock Street, CTR 516, Louisville, KY 40202-1617. Email: [email protected]
Neratinib Alone or in Combination with Immune Checkpoint Inhibitors with or without mTOR Inhibitors in Patients with Fibrolamellar Carcinoma
Authors: Ghassan K Abou-Alfa, Tim Meyer, Richard Kinh Gian Do, Sarina A Piha-Paul, Joseph S Light, Scott Sherrin, Amin Yaqubie, Alison Clemens O'Neill, James J Harding, Raed Al-Rajabi, Crystal S Denlinger, Pablo Cano, Albert S Cornelius, Eileen M O'Reilly, Daniel DiPrimeo, Lisa D Eli, John D Gordan, David B Solit
Journal: Liver Cancer (2024)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Fibrolamellar carcinoma (FLC) displays upregulation of several oncogenes, including &lt;i&gt;HER2&lt;/i&gt;, and multiple immune-suppressive mechanisms. We investigated the efficacy and safety of the pan-HER tyrosine kinase inhibitor neratinib as monotherapy (SUMMIT phase 2 basket study) or with immune checkpoint and/or mammalian target of rapamycin (mTOR) inhibitors (compassionate-use program) in patients with FLC. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Patients received neratinib 240 mg/day orally in SUMMIT, or as doublet or triplet combinations with pembrolizumab 2 mg/kg intravenously every 3 weeks, nivolumab 240 mg intravenously every 2 weeks, everolimus 7.5 mg/day orally, or sunitinib 37.5 mg/day orally under compassionate use. The primary endpoint in SUMMIT was objective response rate; safety was a secondary endpoint. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Fifteen patients with FLC received neratinib monotherapy in SUMMIT. The objective response rate was 5% (95% confidence interval [CI]: 0–21.8) and the disease control rate was 13.3% (95% CI: 1.7–40.5). Upon progression, five had added immune checkpoint inhibitors with or without everolimus or sunitinib. Two additional patients received neratinib-based combinations outside of SUMMIT, for a total of 17 neratinib-treated patients. One patient who received neratinib plus pembrolizumab had a confirmed partial response, one treated with neratinib plus everolimus had stable disease lasting 6 months, and one who received neratinib plus pembrolizumab plus sunitinib had stable disease lasting 16 months. Grade 3/4 adverse events with neratinib monotherapy occurred in 10 (66.7%)/2 (13.3%) patients, respectively. Grade 3 adverse events with neratinib-based combinations were hyperglycemia (&lt;i&gt;n&lt;/i&gt; = 1; neratinib plus pembrolizumab), hepatic failure, and anaphylaxis (&lt;i&gt;n&lt;/i&gt; = 1 each, neratinib plus pembrolizumab plus everolimus). There were no grade 4 adverse events with combination therapy. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; In patients with FLC, single-agent neratinib had limited efficacy, but clinical benefit was observed with neratinib in combination with immunotherapy and/or mTOR-targeted agents.
Abstract 2752: Prevention of Stroke by Antihypertensive Drugs: An Updated Network Meta-analysis
Authors: William J Elliott, Peter M Meyer
Journal: Circulation (2006)

Lowering blood pressure with drug therapy prevents stroke, but whether a specific type of antihypertensive drug is better for this purpose than others has remained controversial. Traditional meta-analyses that include the most recent clinical trial data have shown significantly better stroke prevention with an initial calcium channel blocker (CCB), compared to an initial diuretic/beta-blocker, which in turn is significantly better than an initial angiotensin converting-enzyme (ACE-) inhibitor. Although these meta-analyses show no significant inhomogeneity for stroke, we performed a network meta-analysis (which accounts for both direct and indirect comparisons in clinical trials; Stat Med ., 2002 ; 21 : 2313 ) to compare the relative potency of five classes of initial antihypertensive drugs with placebo. In 64 clinical trials involving 309,657 subjects, initial drug therapy (and the number of patients with new strokes/number of subjects at risk) included: Placebo: 3061 of 67,410 (4.54%); ACE-inhibitor: 1800 of 43,908 (4.10%); angiotensin II receptor blocker (ARB): 817 of 17,124 (4.77%); Beta-blocker: 1916 of 55,810 (3.43%); CCB: 2220 of 74,286 (3.00%); and Diuretic: 1543 of 51,119 (3.02%). Using Placebo as the standard of comparison (39 arms), the incoherence was very small (ω= 0.000009047), and the odds ratios, 95% confidence intervals, and P-values were: Unlike the previous meta-analyses, but similar to the network meta-analysis ( JAMA , 2003 ; : 2534 –44 ) that included data from only 42 trials and 192,478 patients, these results suggest that all antihypertensive drugs significantly prevented stroke in clinical trials, and that an initial calcium antagonist is only slightly (and not significantly) better than an initial diuretic.