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JACC. Case Reports Jul 2024Single coronary artery, giant coronary artery aneurysm, and coronary cameral fistula are rare congenital anomalies, and can cause a range of presentations. To our...
Single coronary artery, giant coronary artery aneurysm, and coronary cameral fistula are rare congenital anomalies, and can cause a range of presentations. To our knowledge, this is the first reported case of all 3 entities occurring simultaneously in 1 patient, with largely unknown implications. Multimodal imaging was essential in prompt diagnosis and management.
PubMed: 38948493
DOI: 10.1016/j.jaccas.2024.102396 -
Frontiers in Surgery 2024Over the course of nearly six decades since the inception of initial trials involving 5-FU in the treatment of mCRC (metastatic colorectal cancer), our progressive... (Review)
Review
Over the course of nearly six decades since the inception of initial trials involving 5-FU in the treatment of mCRC (metastatic colorectal cancer), our progressive comprehension of the pathophysiology, genetics, and surgical techniques related to mCRC has paved the way for the introduction of novel therapeutic modalities. These advancements not only have augmented the overall survival but have also positively impacted the quality of life (QoL) for affected individuals. Despite the remarkable progress made in the last two decades in the development of chemotherapy, immunotherapy, and target therapies, mCRC remains an incurable disease, with a 5-year survival rate of 14%. In this comprehensive review, our primary goal is to present an overview of mCRC treatment methods following the latest guidelines provided by the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), and the American Society of Colon and Rectal Surgeons (ASCRS). Emphasis has been placed on outlining treatment approaches encompassing chemotherapy, immunotherapy, targeted therapy, and surgery's role in managing mCRC. Furthermore, our review delves into prospective avenues for developing new therapies, offering a glimpse into the future of alternative pathways that hold potential for advancing the field.
PubMed: 38948479
DOI: 10.3389/fsurg.2024.1398289 -
Frontiers in Pharmacology 2024Immune checkpoint inhibitors (ICIs), including anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies, have become a standard treatment for multiple cancer types. However,...
Hepatitis-related adverse events associated with immune checkpoint inhibitors in cancer patients: an observational, retrospective, pharmacovigilance study using the FAERS database.
Immune checkpoint inhibitors (ICIs), including anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies, have become a standard treatment for multiple cancer types. However, ICIs can induce immune-related adverse events, with hepatitis-related adverse events (HRAEs) being of particular concern. Our objective is to identify and characterize HRAEs that exhibit a significant association with ICIs using real-world data. In this observational and retrospective pharmacovigilance study, we extracted real-world adverse events reports from the FDA Adverse Event Reporting System database spanning from the first quarter of 2004 to the first quarter of 2023. We conducted both Frequentist and Bayesian methodologies in the framework of disproportionality analysis, which included the reporting odds ratios (ROR) and information components (IC) to explore the intricate relationship between ICIs and HRAEs. Through disproportionality analysis, we identified three categories of HRAEs as being significantly related with ICIs, including autoimmune hepatitis (634 cases, ROR 19.34 [95% CI 17.80-21.02]; IC025 2.43), immune-mediated hepatitis (546 cases, ROR 217.24 [189.95-248.45]; IC025 4.75), and hepatitis fulminant (80 cases, ROR 4.56 [3.65-5.70]; IC025 0.49). The median age of patients who report ICI-related HRAEs was 63 years (interquartile range [IQR] 53.8-72), with a fatal outcome observed in 24.9% (313/1,260) of these reports. Cases pertaining to skin cancer, lung cancer, and kidney cancer constituted the majority of these occurrences. Patients treated with anti-PD-1 or anti-PD-L1 antibodies exhibited a higher frequency of immune-mediated hepatitis in comparison to those undergoing anti-CTLA-4 monotherapy, with a ROR of 3.59 (95% CI 1.78-6.18). Moreover, the dual ICI therapy demonstrated higher reporting rates of ICI-related HRAEs compared to ICI monotherapy. Our findings confirm that ICI treatment carries a significant risk of severe HRAEs, in particular autoimmune hepatitis, immune-mediated hepatitis, and hepatitis fulminant. Healthcare providers should exercise heightened vigilance regarding these risks when managing patients receiving ICIs.
PubMed: 38948476
DOI: 10.3389/fphar.2024.1383212 -
Frontiers in Pharmacology 2024Genomic profiling has revolutionized therapeutic interventions and the clinical management of liver cancer. However, pathogenetic mechanisms, molecular determinants of...
Genomic profiling has revolutionized therapeutic interventions and the clinical management of liver cancer. However, pathogenetic mechanisms, molecular determinants of recurrence, and predictive biomarkers for first-line treatment (anti-PD-(L)1 plus bevacizumab) in liver cancer remain incompletely understood. Targeted next-generation sequencing (tNGS) (a 603-cancer-gene panel) was applied for the genomic profiling of 232 hepatocellular carcinoma (HCC) and 22 intrahepatic cholangiocarcinoma (ICC) patients, among which 47 unresectable/metastatic HCC patients underwent anti-PD-1 plus bevacizumab therapy. Genomic alterations were estimated for their association with vascular invasion (VI), location of onset, recurrence, overall survival (OS), recurrence-free survival (RFS), and anti-PD-1 plus bevacizumab therapy response. The genomic landscape exhibited that the most commonly altered genes in HCC were , , , , , and , while , , , , , and were frequently altered in ICC; notably, (18.18% vs. 1.29%) and (13.64% vs. 1.29%) alterations were significantly more prevalent in ICC. Comparison analysis demonstrated the distinct clinicopathological/genomic characterizations between Chinese and Western HCC cohorts. Genomic profiling of HCC underlying VI showed that , , , , and were frequently altered in the VI group compared to patients without VIs. Compared to the right hepatic lobes of HCC patients, the left hepatic lobe of HCC patients had superior OS (median OS: 36.77 months vs. unreached, < 0.05). By further comparison, Notch signaling pathway-related alterations were significantly prevalent among the right hepatic lobes of HCC patients. Of note, multivariate Cox regression analysis showed that altered , , , , and , as independent prognostic factors, were significantly correlated with the OS of HCC patients. Furthermore, altered was abundantly enriched in the HCC-recurrent group, and impressively, it was independent of clinicopathological features in predicting RFS (median RFS of altered type vs. wild-type: 5.57 months vs. 22.47 months, < 0.01). Regarding those treated HCC patients, TMB value, altered , and cell cycle-related alterations were identified to be positively associated with the objective response rate (ORR), but alterations were negatively correlated with ORR. In addition, altered and cell cycle signaling were significantly associated with reduced and increased time to progression-free survival (PFS), respectively. Comprehensive genomic profiling deciphered distinct molecular characterizations underlying VI, location of onset, recurrence, and survival time in liver cancer. The identification of novel genetic predictors of response to anti-PD-1 plus bevacizumab in HCC facilitated the development of an evidence-based approach to therapy.
PubMed: 38948469
DOI: 10.3389/fphar.2024.1416295 -
Frontiers in Pharmacology 2024Inflammatory bowel disease (IBD) is a chronic condition that can be managed with treatment, but it is challenging to get IBD cured. Resveratrol, a non-flavonoid...
Inflammatory bowel disease (IBD) is a chronic condition that can be managed with treatment, but it is challenging to get IBD cured. Resveratrol, a non-flavonoid polyphenolic organic compound derived from various plants, has a potential effect on IBD. The current research was set out to investigate the therapeutic effects of resveratrol on animal models of IBD. A comprehensive search of PubMed, Embase, Web of Science, and Chinese databases was performed. The literature search process was completed independently by two people and reviewed by a third person. The risk of bias in the included literature was assessed using the Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Stroke (CAMARADES) 10-point quality checklist. The meta-analysis utilized Review Manager 5.4 software to evaluate the efficacy of resveratrol, with histopathological index as the primary outcome measure. Subgroup analysis was conducted based on this indicator. Additionally, meta-analyses were carried out on different outcomes reported in the literature, including final disease activity index, final body weight change, colon length, splenic index, and inflammatory factors. After conducting a thorough literature search and selection process, a total of 28 studies were ultimately included in the analysis. It was found that over half of the selected studies had more than five items with low risk of bias in the bias risk assessment. Relevant datas from included literature indicated that the histopathological index of the resveratrol group was significantly lower than that of the control group (WMD = -2.58 [-3.29, -1.87]). Subgroup analysis revealed that higher doses of resveratrol (>80 mg/kg) had a better efficacy (WMD = -3.47 [-4.97, -1.98]). Furthermore, The data summary and quantitative analysis results of SI and colon length also showed that resveratrol was effective in alleviating intestinal mucosal pathological injury of IBD. In terms of biochemical indicators, the summary analysis revealed that resveratrol affected interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), and prostaglandin E2 (PGE2) significantly. These effects may be attributed to the mechanism of resveratrol in regulating immune response and inhibiting oxidative stress. This review suggests that resveratrol demonstrated a notable therapeutic impact in preclinical models of IBD, particularly at doses exceeding 80 mg/kg. This efficacy is attributed to the protective mechanisms targeting the intestinal mucosa involved in the pathogenesis of IBD through various pathways. As a result, resveratrol holds promising prospects for potential clinical use in the future.
PubMed: 38948464
DOI: 10.3389/fphar.2024.1411566 -
Frontiers in Pharmacology 2024Diabetic nephropathy (DN) constitutes a major microvascular complication of diabetes and is a primary cause of mortality in diabetic individuals. With the global rise in... (Review)
Review
Diabetic nephropathy (DN) constitutes a major microvascular complication of diabetes and is a primary cause of mortality in diabetic individuals. With the global rise in diabetes, DN has become an urgent health issue. Currently, there is no definitive cure for DN. , a Chinese herbal medicine traditionally used, exhibits a wide range of pharmacological effects and is frequently used in the prevention and management of DN. This paper offers an extensive review of the biological mechanisms by which delivers therapeutic advantages in DN management. These mechanisms include activating podocyte autophagy, regulating non-coding RNA, modulating gut microbiota, alleviating lipotoxicity, counteracting oxidative stress, and diminishing inflammatory responses, underscoring the therapeutic potential of in DN treatment.
PubMed: 38948461
DOI: 10.3389/fphar.2024.1390672 -
World Journal of Hepatology Jun 2024Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B (CHB) patients were not previously conducted.
BACKGROUND
Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B (CHB) patients were not previously conducted.
AIM
To assess the liver histological changes in the indeterminate phase CHB patients using liver biopsy.
METHODS
The clinical and laboratory data of 1532 untreated CHB patients were collected, and all patients had least once liver biopsy from January 2015 to December 2021. The significant differences among different phases of CHB infection were compared with -test, and the risk factors of significant liver histological changes were analyzed by the multivariate logistic regression analysis.
RESULTS
Among 1532 untreated CHB patients, 814 (53.13%) patients were in the indeterminate phase. Significant liver histological changes (defined as biopsy score ≥ G2 and/or ≥ S2) were found in 488/814 (59.95%) CHB patients in the indeterminate phase. Significant liver histological changes were significant differences among different age, platelets (PLTs), and alanine aminotransferase (ALT) subgroup in indeterminate patient. Multivariate logistic regression analysis indicated that age ≥ 40 years old [adjust odd risk (aOR), 1.44; 95% confidence interval (CI): 1.06-1.97; = 0.02], PLTs ≤ 150 × 10/L (aOR, 2.99; 95%CI: 1.85-4.83; < 0.0001), and ALT ≥ upper limits of normal (aOR, 1.48; 95%CI: 1.08, 2.05, = 0.0163) were independent risk factors for significant liver histological changes in CHB patients in the indeterminate phase.
CONCLUSION
Our results suggested that significant liver histological changes were not rare among the untreated CHB patients in indeterminate phase, and additional strategies are urgently required for the management of these patients.
PubMed: 38948441
DOI: 10.4254/wjh.v16.i6.920 -
World Journal of Hepatology Jun 2024Non-alcoholic fatty liver disease (NAFLD) increases the risk of cardiovascular diseases independently of other risk factors. However, data on its effect on...
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) increases the risk of cardiovascular diseases independently of other risk factors. However, data on its effect on cardiovascular outcomes in coronavirus disease 2019 (COVID-19) hospitalizations with varied obesity levels is scarce. Clinical management and patient care depend on understanding COVID-19 admission results in NAFLD patients with varying obesity levels.
AIM
To study the in-hospital outcomes in COVID-19 patients with NAFLD by severity of obesity.
METHODS
COVID-19 hospitalizations with NAFLD were identified using International Classification of Disease -10 CM codes in the 2020 National Inpatient Sample database. Overweight and Obesity Classes I, II, and III (body mass index 30-40) were compared. Major adverse cardiac and cerebrovascular events (MACCE) (all-cause mortality, acute myocardial infarction, cardiac arrest, and stroke) were compared between groups. Multivariable regression analyses adjusted for sociodemographic, hospitalization features, and comorbidities.
RESULTS
Our analysis comprised 13260 hospitalizations, 7.3% of which were overweight, 24.3% Class I, 24.1% Class II, and 44.3% Class III. Class III obesity includes younger patients, blacks, females, diabetics, and hypertensive patients. On multivariable logistic analysis, Class III obese patients had higher risks of MACCE, inpatient mortality, and respiratory failure than Class I obese patients. Class II obesity showed increased risks of MACCE, inpatient mortality, and respiratory failure than Class I, but not significantly. All obesity classes had non-significant risks of MACCE, inpatient mortality, and respiratory failure compared to the overweight group.
CONCLUSION
Class III obese NAFLD COVID-19 patients had a greater risk of adverse outcomes than class I. Using the overweight group as the reference, unfavorable outcomes were not significantly different. Morbid obesity had a greater risk of MACCE regardless of the referent group (overweight or Class I obese) compared to overweight NAFLD patients admitted with COVID-19.
PubMed: 38948433
DOI: 10.4254/wjh.v16.i6.912 -
World Journal of Hepatology Jun 2024This editorial describes the milestones to optimize of transjugular intrahepatic portosystemic shunt (TIPS) technique, which have made it one of the main methods for the...
This editorial describes the milestones to optimize of transjugular intrahepatic portosystemic shunt (TIPS) technique, which have made it one of the main methods for the treatment of portal hypertension complications worldwide. Innovative ideas, subsequent experimental studies and preliminary experience of use in cirrhotic patients contributed to the introduction of TIPS into clinical practice. At the moment, the main achievement in optimize of TIPS technique is progress in the qualitative characteristics of stents. The transition from bare metal stents to extended polytetrafluoroethylene-covered stent grafts made it possible to significantly prevent shunt dysfunction. However, the question of its preferred diameter, which contributes to an optimal reduction of portal pressure without the risk of developing post-TIPS hepatic encephalopathy, remains relevant. Currently, hepatic encephalopathy is one of the most common complications of TIPS, significantly affecting its effectiveness and prognosis. Careful selection of patients based on cognitive indicators, nutritional status, assessment of liver function, , will reduce the incidence of post-TIPS hepatic encephalopathy and improve treatment results. Optimize of TIPS technique has significantly expanded the indications for its use and made it one of the main methods for the treatment of portal hypertension complications. At the same time, there are a number of limitations and unresolved issues that require further randomized controlled trials involving a large cohort of patients.
PubMed: 38948432
DOI: 10.4254/wjh.v16.i6.891 -
Integrated Pharmacy Research & Practice 2024Warfarin plays an important role in anticoagulation therapy despite the availability of the newest oral anticoagulants, and achieving optimal anticoagulation is...
PURPOSE
Warfarin plays an important role in anticoagulation therapy despite the availability of the newest oral anticoagulants, and achieving optimal anticoagulation is challenging due to its narrow therapeutic range and variable dose. This study aimed to highlight polypharmacy and drug interactions in patients receiving warfarin therapy at Medani Heart Centre, Sudan.
METHODS
This retrospective hospital-based study was conducted from May 2017 to October 2018. Each concurrent medication prescribed for 104 patients was collected and checked for drug-drug interactions using Medscape Reference-Drug Interaction Checker. The data were analysed by using SPSS 20, and descriptive statistics were used.
RESULTS
The results revealed that 95.2% of patients had more than three medications in their profile, (3-5), (6-9) and more than 10 medications were prescribed for 40.4%, 44.2% and 10.6% of patients, respectively. A total of 93.3% of patients had drug-drug interactions, as follows: (1-5), (6-10), (11-15), (16-20) and more than 20 drug-drug interactions were found in 31.7%, 32.7%, 19.2%, 5.8% and 3.8% of patients, respectively. A total of 178 warfarin-drug interactions were identified in 88.5% of the patients. The INR ranged between 2 and 2.99 in 13.4% of patients, and INR values below 2 and above 5 were found in 44.2% and 21.2% of patients, respectively. Analgesics (n=54; 30.3%), cardiovascular drugs (n=51; 28.6%), and anticoagulants (n=46; 25.8%) were the most common drug classes that interact with warfarin. Significant and serious types of interactions with warfarin were found in 51% and 37.5% of patients, respectively.
CONCLUSION
This study highlights the complexity of managing warfarin therapy amid prevalent polypharmacy. A substantial majority of patients experienced multiple drug interactions. The identification of significant and serious interactions emphasizes the need for vigilant management strategies, including improved communication among healthcare professionals and targeted education for both providers and patients, to enhance the safety and efficacy of warfarin therapy.
PubMed: 38948431
DOI: 10.2147/IPRP.S458827