tbuckley/cabot-search huggingface dataset:
Real-world Child-Pugh scores and outcomes of patients with hepatocellular carcinoma at a high-volume center.
Authors: Ian Tobal, Sameera Shuaibi, Erin Biggs, Jonathan Mizrahi
Journal: Journal of Clinical Oncology (2025)

569 Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and most often occurs in the setting of cirrhosis. Patients (pts) with advanced HCC are not eligible for curative intent therapies such as ablation, surgical resection, or liver transplantation. For the past five years, immune checkpoint inhibitor (ICI)-based systemic therapy regimens have been the mainstay of first-line treatment for pts with advanced HCC. Most trials assessing ICI-containing regimens, including IMBRAVE150 and HIMALAYA, excluded pts with Child-Pugh (CP) scores worse than A. Unfortunately, fewer than half of pts maintain a CP A score at the time of HCC diagnosis and referral to medical oncology. Real-world data on CP scores of patients undergoing ICI-based therapy for advanced HCC at the time of medical oncology referral and treatment start are lacking. Methods: Pts who initiated treatment with either atezolizumab plus bevacizumab (A+B) or durvalumab plus tremelimumab (D+T) in the Ochsner Health system between 1/1/20 and 12/31/23 were included in this analysis. CP scores were calculated at the time of their initial medical oncology visit and again at the time of their first systemic therapy cycle. Pt demographics and clinical outcomes were analyzed. Results: 200 pts were identified in this study, 159 of whom (79.5%) were male. Median age at treatment start was 66.8 years. 117 pts (58.5%) were Caucasian and 63 pts (31.5%) were African American (AA). 152 and 48 pts received A+B and D+T, respectively. At the time of first medical oncology visit, 58 pts (29%) were classified as CP B (n=51) or C (n=7). At the treatment start date, 82 pts (41%) were classified as CP B (n=73) or C (n=9). The median survival across all groups was 10.5 m. Median survival CP A, B, and C pts were 15.4, 7.6, and 1.6 months (m), respectively. 6-month survival rates for CP A, B, and C pts were 75.7%, 52.2%, and 0%, respectively. 12-month survival rates for CP A, B, and C pts were 58.2%, 35.1%, and 0%, respectively. There was no statistically significant difference in CP score at either time point between Caucasian and AA pts. Conclusions: Although pts with CP scores worse than A were not included in the pivotal studies that have established recent standard of care therapies for pts with advanced HCC, a significant proportion of pts being treated with ICI-based regimens have at least CP B liver disease, with a poorer prognosis in that subset of pts. Extremely poor survival rates for those with CP C scores argue against use of ICI-based treatment for these pts. In this analysis, no significant difference was observed in CP scores between Caucasian and AA pts.
Long-term outcomes of total neoadjuvant treatment (TNT) for locally advanced rectal cancer: Maria Sklodowska Curie National Cancer Research Institute (MSCNCRI) cohort from Polish-II study.
Authors: Mariola Winiarek, Katarzyna Marcisz-Grzanka, Lucjan Wyrwicz
Journal: Journal of Clinical Oncology (2025)

84 Background: The data on long-term outcomes of TNT for locally advanced rectal cancer are still limited. The Polish-II study randomized 515 cT4/fixed cT3 rectal cancer to pre-operative chemoradiation (CRT) with 5fu/oxaliplatin or 5x5 Gy radiotherapy with consolidating chemotherapy (TNT). Despite the early separation of survival curves with benefit for TNT, the outcomes at the longer observation were similar reaching 49% in both arms surviving at 8 years. Here, we present the long-term oncological and functional outcomes of patients recruited to the study in MSCNCRI along with the quality of life in survivors at &gt;10 years of observation. Methods: Of 180 patients treated in the study in MSCNCRI 88 and 92 pts were randomized to TNT and CRT arms, respectively. The long-term follow-up was performed according to the standard protocol, FACT-C and EORTC QLQ-C30 scales were used to assess the functional outcomes. Results: Median survival in the TNT group and CRT was 115 and 61 months (p=0.191). At the cut-off in March 2023, 53.4% and 61.1% of pts died in the TNT and CRT group (p = 0.375). In the TNT group, 73.9% of deaths were attributed to cancer corresponding to 81.8% in CRT (p = 0.725). Late relapses diagnosed over 5 years from the end of the active treatment were identified in 5 of 94 patients in the follow-up (1 local recurrence in the TNT group, 4 patients with lung metastasis – 3 in TNT with one having also CNS relapse - and 1 in CRT). All late relapses in the TNT group could be salvaged with local therapies. Regarding long-term quality of life, no differences were observed in FACT-C and EORTC QLQ C30 in patients treated with either arm: QLQ C30 – TNT: 50.68 ± 12.74 in the range 34.00- 79.00; CRT: 48.61 ± 11.39 in the range 34.00-70.00 (p = 0.507); FACT-C - TNT: 113.00 in the range 42.00-136.00; CRT: 118.00 in the range 74.00-136.00; p=0.252). No difference in physical, family, and emotional status was observed. At the ultimate observation, stoma was present in 40.5% and 40.6% of TNT and CRT groups, respectively (p&gt;0.999). Conclusions: In this randomized cohort, after more than 10 years of observation TNT led to numerically longer OS than CRT, although this was not statistically significant. The functional outcomes of the long-term survivors are similar in both cohorts. Late relapses are rare but could be salvaged in most cases. This study further supports the use of TNT in patients with locally advanced rectal cancer. Clinical trial information: NCT00833131 .
Economic burden of hepatocellular carcinoma recurrence after curative treatment in Spain.
Authors: Maria Varela, Jaime Feliú, Margarita Garrido, Miguel Angel Gomez-Bravo, Sonia Gonzalez-Costas, Javier Irurzun, Lucía Ruiz de Alda, Paula Vieitez, David Carcedo, María Crespo, Ruth Vera, Maria Reig
Journal: Journal of Clinical Oncology (2025)

640 Background: The literature on burden of disease studies of hepatocellular carcinoma is scarce. The aim of this analysis was to quantify the economic burden of disease recurrence in very early or early-stage HCC patients who underwent liver resection, ablation or transplantation in Spain. Methods: A decision-tree model was developed to estimate the cost of a recurrence after curative treatment with an initial complete response of very early or early-stage primary HCC tumor over a 5-year time horizon. Clinical parameters were collected by a multidisciplinary group of experts who also validated the assumptions and results of the analysis. According to the Barcelona Clinic Liver Cancer (BCLC) recommendations, patients with recurrent HCC were classified into five HCC stages (0, A, B, C, and D) and allocated to different treatment options. A payer perspective was adopted, so only direct costs (€2024) were considered (local/locoregional treatments costs, drug acquisition and administration costs, adverse events management costs, diagnostic and follow-up costs and end-of-life costs). Sensitivity analyses were performed to assess uncertainty. Results: A total of 1,250 HCC recurrences were estimated in Spain, resulting in a total cost of €32,817,142 in the first year of recurrence management. After 5-years follow-up, an additional €10,1M was estimated, mainly due to patient surveillance (€2,8M) and 228 new recurrences (€5,7M). The average cost of a relapse was €26,253 euros in the first year of recurrence management, rising to €34,342 euros for 5-years follow-up. A hypothetical patient experiencing a second relapse 5 years after their first relapse would incur costs of €58,758. Conclusions: This study is the first in Spain to explore the economic burden of hepatocellular carcinoma. Estimating the cost of recurrence after curative treatment and complete response of a primary HCC tumor is complex and depends on multiple factors, so further studies exploring both efficacy and costs in hepatocellular carcinoma are needed.
Surgical treatment in patients with advanced gastrointestinal stromal tumours (GISTs) in second-line and later stages: A single-centre cohort study.
Authors: Xinhua Zhang, Miao Yan, Yi Lu, Kaiyu Sun, Jinning Ye, Hui Wu, Chuangqi Chen, Shirong Cai, Yulong He
Journal: Journal of Clinical Oncology (2025)

818 Background: Gastrointestinal stromal tumour (GIST) after imatinib treatment failure usually progresses rapidly with limited overall survival. Previous studies have suggested that surgery is beneficial for advanced GISTs in disease control to imatinib, but the role of surgery in &gt; = 2 line patients remains unclear. Methods: Imatinib-resistant patients with advanced GIST between May 2009 and Nov. 2023 were included. Surgical treatments included tumour reduction, radiofrequency ablation and TACE. The primary endpoint was overall survival (OS) and secondary endpoints were time to second-line treatment failure (TTF) and postoperative morbidity. To balance clinicopathological characteristics, 1:1 propensity score matching (PSM) was used. Results: A total of 242 patients with advanced GIST treated with 2nd-line or later drugs were included, including 125 in the surgical group and 117 in the non-surgical group. The median follow-up was 30.3 months. OS was significantly better in the surgical group than in the non-surgical group (pre-PSM: 51.7m vs 35.9m , p = 0.001; post-PSM: 50.8m vs 38.8m, p = 0.043). Univariate analysis showed that surgical treatment (HR 0.487, 95% CI 0.320-0.740, p = 0.001), age ≤60 years (HR 0.640, 95% CI 0.411-0.997, p = 0.049) and low tumour burden (HR 0.491, 95% CI 0.293-0.822, p = 0.007) were associated with prolonged OS. Multivariate analysis indicated that surgical treatment (HR 0.541, 95% CI 0.348-0.843, p = 0.007) and low tumour burden (HR 0.510, 95% CI 0.300-0.865, p = 0.012) were significantly associated with OS benefit. Patients (n = 84) who had surgical treatment during second-line treatment had longer TTF compared to patients (n = 158) who had TKI only (14.2m vs 8.1m , p = 0.003). There were 29 (14.8%) postoperative complications with Clavien-Dindo classification ≥3, including 5 deaths. Conclusions: Surgical treatment can provide a survival benefit for patients with second-line and later advanced GIST, but further studies are needed for a more detailed indication of the surgical population.
Tip-to-Base LAMPOON Procedure for a Valve-in-Valve Transcatheter Mitral Valve Replacement
Authors: Ajmer Singh
Journal: Clinical Cardiology and Cardiovascular Interventions (2024)

Left ventricular outflow tract obstruction is a life-threatening complication of transcatheter mitral valve replacement caused by septal displacement of the anterior mitral leaflet. This complication can be avoided by using of a new technique, called LAMPOON or Laceration of Anterior Mitral leaflet to Prevent left ventricular Outflow ObstructioN. LAMPOON procedure involves splitting the anterior mitral leaflet just before transcatheter mitral valve replacement, which would otherwise be displaced anteriorly by the mitral valve implant and cause left ventricular outflow obstruction. In this case report, we discuss our initial experience with the tip-to-base LAMPOON technique to prevent left ventricular outflow obstruction.
<scp>MHC</scp> Class <scp>II</scp>‐Expressing Mucosal Mast Cells Promote Intestinal Mast Cell Hyperplasia in a Mouse Model of Food Allergy
Authors: Kenji Oishi, Nobuhiro Nakano, Masamu Ota, Eisuke Inage, Kumi Izawa, Ayako Kaitani, Tomoaki Ando, Mutsuko Hara, Yoshikazu Ohtsuka, Chiharu Nishiyama, Hideoki Ogawa, Jiro Kitaura, Ko Okumura, Toshiaki Shimizu
Journal: Allergy (2025)

ABSTRACT Background IgE‐mediated food allergy is accompanied by mucosal mast cell (MMC) hyperplasia in the intestinal mucosa. Intestinal MMC numbers correlate with the severity of food allergy symptoms. However, the mechanisms by which MMCs proliferate excessively are poorly understood. Here, we clarify the role of newly identified MHC class II (MHCII)‐expressing MMCs in the effector phase of IgE‐mediated food allergy. Methods Mice reconstituted with MHCII‐deficient or wild‐type MMCs were used to generate a mouse mode of IgE‐mediated food allergy. We assessed the extent of intestinal MMC hyperplasia and the severity of hypothermia in these mice. In addition, we performed in vitro antigen presentation assay using induced MHCII‐expressing MMCs generated from bone marrow cells to evaluate the effect of CD4 + T cell activation on MMC proliferation. Results In food‐allergic mice, we identified the appearance of MHCII‐expressing MMCs in the intestinal mucosa and showed that MMC hyperplasia was suppressed in mice with MHCII‐deficient MMCs compared to mice with wild‐type MMCs. In vitro assays demonstrated that MHCII‐expressing MMCs incorporate food antigens directly and through the high‐affinity IgE receptor FcεRI‐mediated endocytosis and activate antigen‐specific CD4 + T cells from food‐allergic mice by antigen presentation. Activated CD4 + T cells secrete IL‐4 and large amounts of IL‐5, which enhance production of the mast cell growth factor IL‐9 by IL‐33‐activated MMCs. Excess IL‐9 causes excessive MMC proliferation, leading to the development of MMC hyperplasia. Conclusion Antigen presentation to CD4 + T cells by MHCII‐expressing MMCs triggers intestinal MMC hyperplasia and exacerbates IgE‐mediated food allergy.
Advancements in AI Heart Model Technology: A Comprehensive Review
Authors: Kiran Dudhat
Journal: Clinical Cardiology and Cardiovascular Interventions (2024)

Artificial Intelligence (AI) heart models represent a revolutionary approach in cardiovascular medicine, integrating computational models with machine learning to simulate and analyze heart functions, diagnose conditions, and predict patient outcomes. This manuscript provides a comprehensive review of the advancements in AI heart model technology, encompassing data acquisition, model development, and clinical applications. The paper explores various AI algorithms, from traditional machine learning to deep learning, and discusses their roles in enhancing diagnostic accuracy, personalizing treatments, and advancing research. Key challenges and future directions, including ethical considerations and the integration of AI models into clinical practice, are also examined.
Hypertrophic Cardiomyopathy and Cardiac Arrest Provoked by Low-Intensity Physical Activity – A Case Report
Authors: Petra Knežević
Journal: Clinical Cardiology and Cardiovascular Interventions (2024)

Hypertrophic cardiomyopathy (HCM) is the most prevalent genetic cardiac muscle disorder, predominantly inherited as an autosomal dominant trait due to mutations in sarcomere protein genes. Although HCM is genetically driven, its clinical presentation is marked by significant variability, with a wide range of phenotypic expressions. The condition often presents in childhood, with many patients facing a heightened risk of sudden cardiac death (SCD), particularly during high-intensity physical activity. Given the risks associated with HCM, particularly in the context of high-intensity competitive sports, it is generally recommended that affected individuals avoid such activities. However, even low-intensity physical activity has been associated with SCD, contributing to ongoing debates and unresolved questions within the field.
Yasser's Wenckebach Reversal Phenomenon in a Caudate Nucleus Stroke, COVID-19 Pneumonia, Calculous Cholecystitis, and Ventricular Pacing-A new Cardiovascular Discovery and Interpretation
Authors: Yasser Mohammed Hassanain Elsayed
Journal: Clinical Cardiology and Cardiovascular Interventions (2024)

Rationale: Wenckebach phenomenon is a progressive prolongation of each successive PR interval and is mostly due to a reversible conduction block at the level of the AV node—Malfunctioning AV nodal cells. Caudate nucleus stroke presents with non-progressive symptoms, speech disturbances, chorea, and migraine. COVID-19 infection greatly varies from asymptomatic infection to severe pneumonia. Chronic cholecystitis is a chronic inflammation of the gallbladder resulting in mechanical or physiological dysfunction in its emptying. Ventricle pacing and sensing (VVI) involves ventricles instead of the atrium. If native ventricular activity is sensed then pacing is inhibited. Patient concerns: An elder housewife widow Egyptian female patient presented to the intensive care unit (ICU) with an acute right-side cerebrovascular accident, left-side deviation in the face, migraine, acute confusion, and COVID-19 pneumonia on top of diabetes, hypertension, chronic cholecystitis and ventricle pacing and sensing (VVI). Diagnosis: Yasser's Wenckebach reversal phenomenon in a caudate nucleus stroke, COVID-19 pneumonia, diabetes, hypertension, calculous cholecystitis, and ventricular pacing. Interventions: Chest CT scan, brain CT scan, electrocardiography, oxygenation, and Ventricle pacing. Outcomes: A clinical and electrocardiographic improvement occurred. Lessons Yasser's Wenckebach reversal phenomenon is a new cardiovascular discovery. A caudate nucleus stroke, COVID-19 pneumonia, calculous cholecystitis, and ventricular pacing are associated with the new phenomenon. The normalization of T-wave inversion in anterior leads is also parallel with the reversal of the progressive prolongation of each successive PR interval until a dropped beat from the left to the right. This will signify the Yasser's Wenckebach reversal phenomenon as a signal for the above normalization.
<i>In vitro</i>microbiota model recapitulates and predicts individualised sensitivity to dietary emulsifier
Authors: Héloïse Rytter, Sabrine Naimi, Gary Wu, Jim Lewis, Maeva Duquesnoy, Lucile Vigué, Olivier Tenaillon, Eugeni Belda, Marta Vazquez-Gomez, Nina Touly, Djésia Arnone, Fuhua Hao, Ruth E Ley, Karine Clément, Laurent Peyrin-Biroulet, Andrew D Patterson, Andrew T Gewirtz, Benoit Chassaing
Journal: Gut (2025)

Non-absorbed dietary emulsifiers, including carboxymethylcellulose (CMC), directly disturb intestinal microbiota, thereby promoting chronic intestinal inflammation in mice. A randomised controlled-feeding study (Functional Research on Emulsifiers in Humans, FRESH) found that CMC also detrimentally impacts intestinal microbiota in some, but not all, healthy individuals. This study aimed to establish an approach for predicting an individual's sensitivity to dietary emulsifiers via their baseline microbiota. We evaluated the ability of an in vitro microbiota model (MiniBioReactor Arrray, MBRA) to reproduce and predict an individual donor's sensitivity to emulsifiers. Metagenomes were analysed to identify signatures of emulsifier sensitivity. Exposure of human microbiotas, maintained in the MBRA, to CMC recapitulated the differential CMC sensitivity previously observed in FRESH subjects. Furthermore, select FRESH control subjects (ie, not fed CMC) had microbiotas that were highly perturbed by CMC exposure in the MBRA model. CMC-induced microbiota perturbability was associated with a baseline metagenomic signature, suggesting the possibility of using one's metagenome to predict sensitivity to dietary emulsifiers. Transplant of human microbiotas that the MBRA model deemed CMC-sensitive, but not those deemed insensitive, into IL-10-/- germfree mice resulted in overt colitis following CMC feeding. These results suggest that an individual's sensitivity to emulsifier is a consequence of, and can thus be predicted by, examining their baseline microbiota, paving the way to microbiota-based personalised nutrition.
Factors Related to The Perception of Hospital Noise in A Neuroscience Unit
Authors: Rodríguez- Nogueiras
Journal: Clinical Cardiology and Cardiovascular Interventions (2024)

Noise has doubled in recent decades; technological advances being its main cause. This means that the figures are well above the recommendations stipulated by the World Health Organization (WHO), which are 35 dB during the day, and 30 dB at night.
CircPRKD3-loaded exosomes concomitantly elicit tumor growth inhibition and glioblastoma microenvironment remodeling via inhibiting STAT3 signaling
Authors: Xiaoming Zhang, Mengyuan Jiang, Wanxiang Niu, Ben Xu, Ce Zhang, Minglong Yang, Shanshan Hu, Chaoshi Niu
Journal: Neuro-Oncology (2025)

Abstract Background Glioblastoma stem cells (GSCs) and their exosomes (exos) are involved in shaping the immune microenvironment, which is important for tumor invasion and recurrence. However, studies involving GSC-derived exosomal circular RNAs (GDE-circRNAs) in regulating tumor microenvironment (TME) remain unknown. Here, we comprehensively evaluated the significance of a novel immune-related GDE-circRNA in glioma microenvironment. Methods GDE-circPRKD3 was screened out through high-throughput sequencing and verified by RT-PCR, sanger sequencing and RNase R assays. A series of in vitro and in vivo experiments were performed to investigate the function of GDE-circPRKD3. RNA-seq, RNA immunoprecipitation, multicolor flow cytometry and western blotting were used to explore the regulation of GDE-circPRKD3 on STAT3 signaling-mediated TME remodeling. Results We have characterized a circRNA PRKD3 in GSC exosomes, and lower circPRKD3 expression predicts a worse prognosis for glioblastoma patients. Overexpression of GDE-circPRKD3 significantly impairs the biological competence of glioma and prolongs the survival of xenograft mice. GDE-circPRKD3 binds to HNRNPC in an m6A-dependent manner, accelerates mRNA decay of IL6ST and inhibits downstream target STAT3. Notably, GDE-circPRKD3 promotes CXCL10 secretion by reprogramming tumor-associated macrophages, which in turn recruits CD8+ tumor infiltrating lymphocytes against GBM. Moreover, brain-targeted lipid nanoparticle delivery of circPRKD3 combined with immune checkpoint blockade therapy achieves significant combinatorial benefits. Conclusion This study provides a novel mechanism by which GDE-circPRKD3 relies on STAT3 signaling to remodel immunosuppressive TME and offers a potential RNA immunotherapy strategy for GBM treatment.