Impact of frailty on endoscopic retrograde cholangiopancreatography outcomes in nonagenarians:A United States national experience

BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP)is an essential therapeutic tool for biliary and pancreatic diseases.Frail and elderly patients,especially those aged≥90 years are generally considered a higher-risk population for ERCP-related complications.AIM To investigate outcomes of ERCP in the Non-agenarian population(≥90 years)concerning Frailty.METHODS This is a cohort study using the 2018-2020 National Readmission Database.Patients aged≥90 were identified who underwent ERCP,using the international classification of diseases-10 code with clinical modification.Johns Hopkins’s adjusted clinical groups frailty indicator was used to classify patients as frail and non-frail.The primary outcome was mortality,and the secondary outcomes were morbidity and the 30 d readmission rate related to ERCP.We used univariate and multivariate regression models for analysis.RESULTS A total of 9448 patients were admitted for any indications of ERCP.Frail and non-frail patients were 3445(36.46%)and 6003(63.53%)respectively.Indications for ERCP were Choledocholithiasis(74.84%),Biliary pancreatitis(9.19%),Pancreatico-biliary cancer(7.6%),Biliary stricture(4.84%),and Cholangitis(1.51%).Mortality rates were higher in frail group[adjusted odds ratio(aOR)=1.68,P=0.02].The Intra-procedural complications were insigni-ficant between the two groups which included bleeding(aOR=0.72,P=0.67),accidental punctures/lacerations(aOR=0.77,P=0.5),and mechanical ventilation rates(aOR=1.19,P=0.6).Post-ERCP complication rate was similar for bleeding(aOR=0.72,P=0.41)and post-ERCP pancreatitis(aOR=1.4,P=0.44).Frail patients had a longer length of stay(6.7 d vs 5.5 d)and higher mean total charges of hospitalization($78807 vs$71392)compared to controls(P<0.001).The 30 d all-cause readmission rates between frail and non-frail patients were similar(P=0.96).CONCLUSION There was a significantly higher mortality risk and healthcare burden amongst nonagenarian frail patients undergoing ERCP compared to non-frail.Larger studies are warranted to investigate and mitigate modifiable risk factors.

Hepatocellular carcinoma national burden across different geographical regions in the United States between 2001 and 2020

BACKGROUND While prior data showed an increasing incidence of hepatocellular carcinoma(HCC)in the United States,there are limited comprehensive and comparative data on the geographical variations of HCC trends in different demographicspecific populations.AIM To evaluate sex and age-specific incidence rates and time trends in different geographical regions in the United States.METHODS Age-adjusted HCC incidence rates were collected from the United States Cancer Statistics(USCS)database which covers approximately 98%of the population in the United States.HCC rates were stratified by sex,age,and geographical region.annual percentage change(APC)and average APC(AAPC)were estimated using Joinpoint Regression.A pairwise comparison was conducted between sex-specific trends.RESULTS There were 467344 patients diagnosed with HCC in the United States in the USCS database between 2001 and 2020.The rates and trends varied by geographical region.When looking at the West region(115336 patients),incidence rates of HCC were overall increasing and also increasing in older adults.However,when evaluating younger adults,HCC incidence rates decreased in men but not in women with a sex-specific absolute AAPC-difference of 2.15(P=0.005).When evaluating the Midwest region(84612 patients),similar results were seen.While incidence rates were increasing in the overall population and in older adults as well,they were decreasing in younger men but not in women with a sex-specific absolute AAPC-difference of 1.61(P<0.001).For the Northeast region(87259 patients),the analysis showed similar results with decreasing HCC incidence rates in younger men but not counterpart women(Sex-specific AAPC-difference=3.26,P<0.001).Lastly,when evaluating the south(180137 patients),the results were also decreasing in younger men but not in women(Sex-specific AAPC-difference=2.55,P<0.001).CONCLUSION Nationwide analysis covering around 98%of the United States population shows an increasing incidence of HCC across all geographical regions,most notably in the South.While younger men experienced decreasing HCC incidence,younger women had a stable trend and this was noted across all regions as well.Our study offers insight into the epidemiology of HCC in different demographic groups across various United States geographical regions.While the reasons contributing to our findings are unclear,they can be related to sex and regional disparities in healthcare access and utilization.Future research is warranted to characterize the temporal change in HCC risk factors across different United States regions.

Evolution of heart transplant donor characteristics in the 21st century: A United States single center’s experience

Despite a record setting number of heart transplants performed annually,the national donor shortage continues to plague transplant teams across the United States.Here we describe the barriers to adaptation of numerous“non-traditional”orthotopic heart transplant donor characteristics including donors with hepatitis C virus,those meeting criteria for donation after cardiac death,donors with coronavirus disease 19 infection,donors with the human immunodeficiency virus,and grafts with left ventricular systolic dysfunction.Our center’s objective was to increase our transplant volume by expanding our donor pool from“traditional”donors to these“non-traditional”donors.We detail how medical advances such as certain laboratory studies,pharmacologic interventions,and organ care systems have allowed our center to expand the donor pool thereby increasing transplantation volume without adverse effects on outcomes.

Mitigating the Prevalence of Diabetic Retinopathy in the United States: Utilization of the Chronic Care Model as a Public Health Framework

As the prevalence of diabetic retinopathy continues to be on the rise, the Chronic Care Model (CCM) offers a transformative, patient-focused approach for efficient diabetic retinopathy care, emphasizing the need for urgent and innovative strategies in the United States. The model integrates community resources, healthcare organizations, self-management support, delivery system design, decision support, and clinical information systems. Addressing challenges and solutions, the model emphasizes proactive and preventive measures, collaborative multidisciplinary care, technological integration, and overcoming resistance to change. This paper proposes the utilization of the Chronic Care Model (CCM) as a possible public health framework for comprehensive management of diabetic retinopathy in the United States. Implementing the CCM offers a comprehensive approach to diabetic retinopathy care, addressing both individual and systemic factors, essential for improving public health outcomes.

Sex and racial disparities in non-alcoholic fatty liver disease-related cardiovascular events: National inpatient sample analysis (2019)

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)increases cardiovascular disease(CVD)risk irrespective of other risk factors.However,large-scale cardiovascular sex and race differences are poorly understood.AIM To investigate the relationship between NAFLD and major cardiovascular and cerebrovascular events(MACCE)in subgroups using a nationally representative United States inpatient sample.METHODS We examined National Inpatient Sample(2019)to identify adult hospitalizations with NAFLD by age,sex,and race using ICD-10-CM codes.Clinical and demographic characteristics,comorbidities,and MACCE-related mortality,acute myocardial infarction(AMI),cardiac arrest,and stroke were compared in NAFLD cohorts by sex and race.Multivariable regression analyses were adjusted for sociodemographic characteristics,hospitalization features,and comorbidities.RESULTS We examined 409130 hospitalizations[median 55(IQR 43-66)years]with NFALD.NAFLD was more common in females(1.2%),Hispanics(2%),and Native Americans(1.9%)than whites.Females often reported non-elective admissions,Medicare enrolment,the median age of 55(IQR 42-67),and poor income.Females had higher obesity and uncomplicated diabetes but lower hypertension,hyperlipidemia,and complicated diabetes than males.Hispanics had a median age of 48(IQR 37-60),were Medicaid enrollees,and had non-elective admissions.Hispanics had greater diabetes and obesity rates than whites but lower hypertension and hyperlipidemia.MACCE,all-cause mortality,AMI,cardiac arrest,and stroke were all greater in elderly individuals(P<0.001).MACCE,AMI,and cardiac arrest were more common in men(P<0.001).Native Americans(aOR 1.64)and Asian Pacific Islanders(aOR 1.18)had higher all-cause death risks than whites.CONCLUSION Increasing age and male sex link NAFLD with adverse MACCE outcomes;Native Americans and Asian Pacific Islanders face higher mortality,highlighting a need for tailored interventions and care.

Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival

BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.

Type-B monoamine oxidase inhibitors in neurological diseases:clinical applications based on preclinical findings

Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.

Diagnostic challenges and individualized treatment of cervical adenocarcinoma metastases to the breast:A case report

BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in literature.Breast metastases are associated with poor prognosis.The following case highlights the diagnostic challenges associated with metastatic cervical cancer to the breast along with individualized treatment.CASE SUMMARY A 44-year-old G7P5025 with no significant past medical or surgical history presented with heavy vaginal to an outside emergency department where an exam and a pelvic magnetic resonance imaging showed a 4.5 cm heterogenous lobulated cervical mass involving upper two thirds of vagina,parametria and lymph node metastases.Cervical biopsies confirmed high grade adenocarcinoma with mucinous features.A positron emission tomography/computed tomography(PET/CT)did not show evidence of metastatic disease.She received concurrent cisplatin with external beam radiation therapy.Follow up PET/CT scan three months later showed no suspicious fluorodeoxyglucose uptake in the cervix and no evidence of metastatic disease.Patient was lost to follow up for six months.She was re-imaged on re-presentation and found to have widely metastatic disease including breast disease.Breast biopsy confirmed programmed death-ligand 1 positive metastatic cervical cancer.The patient received six cycles of carboplatin and paclitaxel with pembrolizumab.Restaging imaging demonstrated response.Patient continued on pembrolizumab with disease control.CONCLUSION Metastatic cervical cancer to the breast is uncommon with nonspecific clinical findings that can make diagnosis challenging.Clinical history and immunohistochemical evaluation of breast lesion,and comparison to primary tumor can support diagnosis of metastatic cervical cancer to the breast.Overall,the prognosis is poor,but immunotherapy can be considered in select patients and may result in good disease response.

Use of machine learning models for the prognostication of liver transplantation: A systematic review

BACKGROUND Liver transplantation(LT)is a life-saving intervention for patients with end-stage liver disease.However,the equitable allocation of scarce donor organs remains a formidable challenge.Prognostic tools are pivotal in identifying the most suitable transplant candidates.Traditionally,scoring systems like the model for end-stage liver disease have been instrumental in this process.Nevertheless,the landscape of prognostication is undergoing a transformation with the integration of machine learning(ML)and artificial intelligence models.AIM To assess the utility of ML models in prognostication for LT,comparing their performance and reliability to established traditional scoring systems.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines,we conducted a thorough and standardized literature search using the PubMed/MEDLINE database.Our search imposed no restrictions on publication year,age,or gender.Exclusion criteria encompassed non-English studies,review articles,case reports,conference papers,studies with missing data,or those exhibiting evident methodological flaws.RESULTS Our search yielded a total of 64 articles,with 23 meeting the inclusion criteria.Among the selected studies,60.8%originated from the United States and China combined.Only one pediatric study met the criteria.Notably,91%of the studies were published within the past five years.ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values(ranging from 0.6 to 1)across all studies,surpassing the performance of traditional scoring systems.Random forest exhibited superior predictive capabilities for 90-d mortality following LT,sepsis,and acute kidney injury(AKI).In contrast,gradient boosting excelled in predicting the risk of graft-versus-host disease,pneumonia,and AKI.CONCLUSION This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT,marking a significant evolution in the field of prognostication.

Vonoprazan-amoxicillin dual regimen with Saccharomyces boulardii as a rescue therapy for Helicobacter pylori:Current perspectives and implications

Yu et al’s study in the World Journal of Gastroenterology(2023)introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii(S.boulardii)for the rescue therapy against Helicobacter pylori(H.pylori),a pathogen responsible for peptic ulcers and gastric cancer.Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression,which is minimally affected by mealtime.Compared to proton pump inhibitors,which bind irreversibly to cysteine residues in the H+/K+-ATPase pump,Vonoprazan competes with the K+ions,prevents the ions from binding to the pump and blocks acid secretion.Concerns with increasing antibiotic resistance,effects on the gut microbiota,patient compliance,and side effects have led to the advent of a dual regimen for H.pylori.Previous studies suggested that S.boulardii plays a role in stabilizing the gut barrier which improves H.pylori eradication rate.With an acceptable safety profile,the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile,thereby strengthening the applicability in clinical settings.Nonetheless,S.boulardii comes in various formulations and dosages,warranting further exploration into the optimal dosage for supplementation in rescue therapy.Additionally,larger,randomized,double-blinded controlled trials are warranted to confirm these promising results.

Impact of microplastics and nanoplastics on liver health:Current understanding and future research directions

With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.

Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review

Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice.Data sources:The search was conducted in PubMed,Embase,Cochrane,and LILACS.The related references were searched manually.Inclusion criteria were:reports in English or Portuguese literature that a)patients with confirmed diagnosis of phCCC;b)patients treated with a curative intent;c)patients with the outcomes of liver resection and liver transplantation.Case reports,reviews,letters,editorials,conference abstracts and papers with full-text unavailability were excluded from the analysis.Results:Most of the current literature is based on observational retrospective studies with low grades of evidence.Liver resection has better long-term outcomes than systemic chemotherapy or palliation ther-apy and liver transplantation is a good alternative for selected patients with unresectable phCCC.All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahep-atic diseases.As a general rule,patients presenting with a tumor having a longitudinal size>3 cm or extending below the cystic duct,lymph node disease,confirmed extrahepatic dissemination;intraoper-atively diagnosed metastatic disease;a history of other malignancies within the last five years,and did not complete chemoradiation regimen and were medically unfit should not be considered for transplan-tation.Some of these criteria should be individually assessed.Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers,and any decision-making must be based on a multidisciplinary evaluation.Conclusions:phCCC is a complex condition with high morbidity.Surgical therapies,including hepatec-tomy and liver transplantation,are the best option for better long-term disease-free survival.

Burden of gallstone disease in the United States population:Prepandemic rates and trends

BACKGROUND Gallstone disease is one of the most common digestive disorders in the United States and leads to significant morbidity,mortality,and health care utilization.AIM To expand on earlier findings and investigate prepandemic rates and trends in the gallstone disease burden in the United States using national survey and claims databases.METHODS The National Ambulatory Medical Care Survey,National Inpatient Sample,Nationwide Emergency Department Sample,Nationwide Ambulatory Surgery Sample,Vital Statistics of the United States,Optum Clinformatics®Data Mart,and Centers for Medicare and Medicaid Services Medicare 5%Sample and Medicaid files were used to estimate claims-based prevalence,medical care including cholecystectomy,and mortality with a primary or other gallstone diagnosis.Rates were age-adjusted(for national databases)and shown per 100000 population.RESULTS Gallstone disease prevalence(claims-based,2019)was 0.70%among commercial insurance enrollees,1.03%among Medicaid beneficiaries,and 2.09%among Medicare beneficiaries and rose over the previous decade.Recently,in the United States population,gallstone disease contributed to approximately 2.2 million ambulatory care visits,1.2 million emergency department visits,625000 hospital discharges,and 2000 deaths annually.Women had higher medical care rates with a gallstone disease diagnosis,but mortality rates were higher among men.Hispanics had higher ambulatory care visit and hospital discharge rates compared with Whites,but not mortality rates.Blacks had lower ambulatory care visit and mortality rates,but similar hospital discharge rates compared with whites.During the study period,ambulatory care and emergency department visit rates with a gallstone disease diagnosis rose,while hospital discharge and mortality rates declined.Among commercial insurance enrollees,rates were higher compared with national data for ambulatory care visits and hospitalizations,but lower for emergency department visits.Cholecystectomies performed in the United States included 605000 ambulatory laparoscopic,280000 inpatient laparoscopic,and 49000 inpatient open procedures annually.Among commercial insurance enrollees,rates were higher compared with national data for laparoscopic procedures.CONCLUSION The gallstone disease burden in the United States is substantial and increasing,particularly among women,Hispanics,and older adults with laparoscopic cholecystectomy as the mainstay treatment.Current practice patterns should be monitored for better health care access.

MicroRNAs in hepatocellular carcinoma treatment:Charting the path forward

MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like other tumors,seldom occurs in isolation;instead,it evolves within a microenvironment featuring oncogenic and tumor-suppressive elements.When combined with suitable delivery vehicles,miRNA technology provides the capability to directly engage with these elements,thereby hindering tumor formation and progression.Ongoing research in this domain holds the promise of enabling a more efficacious and multi-modal treatment approach for HCC in the near future.

Radiotherapy for hyoid bone metastasis from lung adenocarcinoma:A case report

BACKGROUND Metastasis to the hyoid bone is an exceptionally rare occurrence,with documented cases limited to breast,liver,colon,skin,lung,and prostate cancers.This report highlights an unusual case involving the metastasis of lung adenocarcinoma to the hyoid bone,accompanied by a distinctive headache.Previous documentation involved surgical resection of the hyoid mass.We present a case displaying the benefits of palliative radiotherapy.CASE SUMMARY A 72-year-old non-smoking,non-alcoholic woman,initially under investigation for a year-long elevation in absolute lymphocyte count,presented with a monthlong history of intermittent throat pain.Despite negative findings in gastroenterological and otolaryngologic examinations,a contrast-enhanced chest computed tomography scan revealed a mediastinal mass and questionable soft tissue thickening in her left anterolateral neck.Subsequent imaging and biopsies confirmed the presence of lung adenocarcinoma metastasis to the hyoid bone.The patient was treated with platinum-based chemo-immunotherapy along with pembrolizumab.Ultimately,the lung cancer was unresponsive.Our patient opted for palliative radiation therapy instead of surgical resection to address her throat pain.As a result,her throat pain was alleviated,and it also incidentally resolved her chronic headaches.This is the second documented case of lung adenocarcinoma metastasizing to the hyoid bone.CONCLUSION Palliative radiotherapy may add to the quality of life in symptomatic patients with cancer metastatic to the hyoid bone.

Inferior outcomes of liver transplantation for hepatocellular carcinoma during early-COVID-19 pandemic in the United States

BACKGROUND Early in the coronavirus disease 2019(COVID-19)pandemic,there was a significant impact on routine medical care in the United States,including in fields of transplantation and oncology.AIM To analyze the impact and outcomes of early COVID-19 pandemic on liver transplantation(LT)for hepatocellular carcinoma(HCC)in the United States.METHODS WHO declared COVID-19 as a pandemic on March 11,2020.We retrospectively analyzed data from the United Network for Organ Sharing(UNOS)database regarding adult LT with confirmed HCC on explant in 2019 and 2020.We defined pre-COVID period from March 11 to September 11,2019,and early-COVID period as from March 11 to September 11,2020.RESULTS Overall,23.5%fewer LT for HCC were performed during the COVID period(518 vs 675,P<0.05).This decrease was most pronounced in the months of March-April 2020 with a rebound in numbers seen from May-July 2020.Among LT recipients for HCC,concurrent diagnosis of non-alcoholic steatohepatitis significantly increased(23 vs 16%)and alcoholic liver disease(ALD)significantly decreased(18 vs 22%)during the COVID period.Recipient age,gender,BMI,and MELD score were statistically similar between two groups,while waiting list time decreased during the COVID period(279 days vs 300 days,P=0.041).Among pathological characteristics of HCC,vascular invasion was more prominent during COVID period(P<0.01),while other features were the same.While the donor age and other characteristics remained same,the distance between donor and recipient hospitals was significantly increased(P<0.01)and donor risk index was significantly higher(1.68 vs 1.59,P<0.01)during COVID period.Among outcomes,90-day overall and graft survival were the same,but 180-day overall and graft were significantly inferior during COVID period(94.7 vs 97.0%,P=0.048).On multivariable Coxhazard regression analysis,COVID period emerged as a significant risk factor of post-transplant mortality(Hazard ratio 1.85;95%CI:1.28-2.68,P=0.001).CONCLUSION During COVID period,there was a significant decrease in LTs performed for HCC.While early postoperative outcomes of LT for HCC were same,the overall and graft survival of LTs for HCC after 180 days were significantly inferior.

Recent advances in the diagnosis of drug-induced liver injury

Drug-induced liver injury(DILI)is a major problem in the United States,commonly leading to hospital admission.Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between drug exposure and liver injury and a thorough work up for other causes.In addition,DILI has a very variable clinical and histologic presentation that can mimic many different etiologies of liver disease.Objective scoring systems can assess the probability that a drug caused the liver injury but liver biopsy findings are not part of the criteria used in these systems.This review will address some of the recent updates to the scoring systems and the role of liver biopsy in the diagnosis of DILI.

Peptic ulcer disease in non-alcoholic fatty liver disease hospitalizations:A new challenge on the horizon in the United States

BACKGROUND Peptic ulcer disease(PUD)is frequently seen in patients with liver cirrhosis.However,current literature lacks data on PUD in non-alcoholic fatty liver disease(NAFLD)hospitalizations.AIM To identify trends and clinical outcomes of PUD in NAFLD hospitalizations in the United States.METHODS The National Inpatient Sample was utilized to identify all adult(≥18 years old)NAFLD hospitalizations with PUD in the United States from 2009-2019.Hospitalization trends and outcomes were highlighted.Furthermore,a control group of adult PUD hospitalizations without NAFLD was also identified for a comparative analysis to assess the influence of NAFLD on PUD.RESULTS The total number of NAFLD hospitalizations with PUD increased from 3745 in 2009 to 3805 in 2019.We noted an increase in the mean age for the study population from 56 years in 2009 to 63 years in 2019(P<0.001).Racial differences were also prevalent as NAFLD hospitalizations with PUD increased for Whites and Hispanics,while a decline was observed for Blacks and Asians.The all-cause inpatient mortality for NAFLD hospitalizations with PUD increased from 2%in 2009 to 5%in 2019(P<0.001).However,rates of Helicobacter pylori(H.pylori)infection and upper endoscopy decreased from 5%in 2009 to 1%in 2019(P<0.001)and from 60%in 2009 to 19%in 2019(P<0.001),respectively.Interestingly,despite a significantly higher comorbidity burden,we observed lower inpatient mortality(2%vs 3%,P=0.0004),mean length of stay(LOS)(11.6 vs 12.1 d,P<0.001),and mean total healthcare cost(THC)($178598 vs$184727,P<0.001)for NAFLD hospitalizations with PUD compared to non-NAFLD PUD hospitalizations.Perforation of the gastrointestinal tract,coagulopathy,alcohol abuse,malnutrition,and fluid and electrolyte disorders were identified to be independent predictors of inpatient mortality for NAFLD hospitalizations with PUD.CONCLUSION Inpatient mortality for NAFLD hospitalizations with PUD increased for the study period.However,there was a significant decline in the rates of H.pylori infection and upper endoscopy for NAFLD hospitalizations with PUD.After a comparative analysis,NAFLD hospitalizations with PUD had lower inpatient mortality,mean LOS,and mean THC compared to the non-NAFLD cohort.

Real-world clinical effectiveness of sorafenib among patients with unresectable hepatocellular carcinoma at two centers in the United States

BACKGROUND In the United States,sorafenib monotherapy was approved in 2007 for first-line(1L)treatment of patients with unresectable hepatocellular carcinoma(uHCC).As other therapies have been approved in recent years for hepatocellular carcinoma treatment in later lines,it is essential to assess clinical effectiveness of older therapies in actual clinical practice to inform healthcare practitioners’decisions for better patient care.AIM To assess patient characteristics/clinical effectiveness of 1L sorafenib in uHCC patients treated in United States academic and community practice settings.METHODS A retrospective observational study was conducted among adult patients(≥18 years)in the United States initiating sorafenib monotherapy as 1L systemic therapy for uHCC with Eastern Cooperative Oncology Group status of 0 or 1 between January 2016 and December 2019 at City of Hope and Advent Health.Data were extracted by trained abstractionists from individual patients’electronic health records and captured in electronic case report forms.Institutional Review Board approvals were obtained prior to study initiation.Data were captured from the time of sorafenib initiation until death or the end of follow-up.All data were de-identified prior to analyses.Clinical outcomes assessed included provider-reported best response,progression-free survival(PFS),and overall survival(OS).PFS and OS were estimated using Kaplan-Meier methods.RESULTS Among 134 uHCC patients treated with 1L sorafenib,majority were male(75%),and most were Caucasian(62%)or Asian(19%).Median patient age was 64 years.The most common etiologies of liver disease were hepatitis C(54%),alcohol-related liver disease(16%),and hepatitis B(11%).Most patients were reported to have Barcelona Clinic Liver Cancer stage B(19%)or stage C(70%)disease.Of 134 patients,110(82%)were reported to have discontinued treatment or died during follow-up.Primary reasons for sorafenib discontinuation were reported as progression(35%)and toxicity(30%).Best overall response was reported for 124 patients,of which 7.3%reported complete or partial response.Median time to treatment discontinuation was 2.3 mo.Overall,103 patients(77%)had disease progression or died during sorafenib therapy.Median PFS was estimated to be 2.9 mo.At the end of follow-up,82 patients(61%)were deceased.Median OS was 8.5 mo.CONCLUSION Newer therapeutic options that have reported higher PFS and OS in real-world clinical practice should be considered to enhance patient outcomes.

Immunotherapy of gastric cancer:Present status and future perspectives

In this editorial,we comment on the article entitled“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review(1999-2023),”which was published in the recent issue of the World Journal of Gastroenterology.We focused on the results of the authors’bibliometric analysis concerning gastric cancer immunotherapy,which they analyzed in depth by compiling the relevant publications of the last 20 years.Before that,we briefly describe the most recent data concerning the epidemiological parameters of gastric cancer(GC)in different countries,attempting to give an interpretation based on the etiological factors involved in the etiopathogenesis of the neoplasm.We then briefly discuss the conservative treatment(chemotherapy)of the various forms of this malignant neoplasm.We describe the treatment of resectable tumors,locally advanced neoplasms,and unresectable(advanced)cases.Special attention is given to modern therapeutic approaches with emphasis on immunotherapy,which seems to be the future of GC treatment,especially in combination with chemotherapy.There is also a thorough analysis of the results of the study under review in terms of the number of scientific publications,the countries in which the studies were conducted,the authors,and the scientific centers of origin,as well as the clinical studies in progress.Finally,an attempt is made to draw some conclusions and to point out possible future directions.