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Journal of Geriatric Cardiology 2015年第1期12卷 57-65页

作者： Carol Chen-Scarabelli Louis Saravolatz Benjamin Hirsh pratik agrawal Tiziano M. Scarabelli Veterans Affairs Healthcare System Ann Arbor 2215 Fuller Rd. Ann Arbor M148105 USA St. John Hospital and Medical Center~Wayne State University 22101 Moross Rd. Detroit M148236 USA Zena and Michael A. Wiener Cardiovascular Institute Mount Sinai Medical Center One Gustave L. Levy Place Box 1030 New York NY 10029-6574 USA

Heart failure （HF）, a complex clinical syndrome due to structural or functional disorder of the heart, is a major global health issue, with a prevalence of over 5.8 million in the USA alone, and over 23 million worldwide. As a leading cause of hospitalizations among patients aged 65 years or older, HF is a major consumer of healthcare resources, creating a substantial strain on the healthcare system. This paper discusses the epidemiology of HF, financial impact, and multifaceted predicaments in end-stage HF care. A search was conducted on the U.S National Library of Medicine website （***） using keywords such as end-stage heart failure, palliative care, ethical dilemmas. Despite the poor prognosis of HF （worse than that for many cancers）, many HF patients, caregivers, and clinicians are unaware of the poor prognosis. In addition, the unpredictable clinical trajectory of HF complicates the planning of end-of-life care, such as palliative care and hospice, leading to underutilization of such resources. In conclusion, ethical dilemmas in end-stage HF are numerous, embroiling not only the patient, but also the caregiver, healthcare team, and society.

关键词： Ethical dilemmas Heart failure Palliative care

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The role and modulation of autophagy in experimental models of myocardial ischemia-reperfusion injury

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Journal of Geriatric Cardiology 2014年第4期11卷 338-348页

作者： Carol Chen-Scarabelli pratik R. agrawal Louis Saravolatz Cadigia Abuniat Gabriele Scarabelli Anastasis Stephanou Leena Loomba Jagat Narula Tiziano M. Scarabelli Richard Knight VA Ann Arbor Health Care System University of Michigan 2215 Fuller Rd Ann Arbor M148105 USA Zena and Michael A. Wiener Cardiovascular Institute Mount Sinai Medical Center One Gustave L. Levy Place Box 1030 New York NY 10029-6574 USA St John Hospital and Medical Center Wayne State University School of Medicine 22101 Moross Rd. Detroit M148236 USA Medical and Molecular Biology Unit University College London UCL 30 Guildford St. London WC1N 1EH UK

A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cyto-plasmic constituents, and contributes significantly to the degree of myocardial ischemia-reperfusion （I/R） injury. This tightly orchestrated cata-bolic cellular‘housekeeping’ process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protec-tive mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the va-riability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin （mTOR） inhibitors, adenosine monophosphate-activated protein kinase （AMPK） modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic ma-nipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling.

关键词： Autophagy Heart Ischemia-reperfusion injury Cell survival

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Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease

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Journal of Geriatric Cardiology 2016年第8期13卷 701-711页

作者： Giovanni Corsetti Evasio Pasini Tiziano M Scarabelli Claudia Romano pratik R agrawal Carol Chen-Scarabelli Richard Knight Louis Saravolatz Jagat Narula Mario Ferrari-Vivaldi Vincenzo Flati Deodato Assanelli Francesco S Dioguardi Department of Clinical & Experimental Sciences Division of Human Anatomy & Physiopathology University of Brescia Brescia Italy 'S.Maugeri Foundation ' IRCCS Cardiology Division Medical Centre of Lumezzane Brescia Italy Zena and Michael A Wiener Cardiovascular Institute Mount Sinai Medical Center New York USA Center for Heart and Vessel Preclinical Studies St. John Hospital & Medical Center Wayne State University School of Medicine Detroit USA VA Ann Arbor Health Care System University of Michigan Ann Arbor USA Department of Cardiovascular Surgery 'San Rocco' Hospital Ome Brescia Italy Department of Biotechnological and Applied Clinical Sciences University of L 'Aquila L 'Aquila Italy Division of Sport-Internal Medicine Department of Clinical & Experimental Sciences University of Brescia Brescia Italy Department of Clinical Sciences and Community Health University of Milan Milan Italy

Background Klotho proteins （α- and β） are membrane-based circulating proteins that regulate cell metabolism, as well as the lifespan modulating activity of Fibroblast Growth Factors （FGFs）. Recent data has shown that higher plasma circulating Klotho levels reduce cardio- vascular risk, suggesting Klotho has a protective role in cardiovascular diseases. However, although so far it has been identified in various organs, it is unknown whether cardiomyocytes express Klotho and FGFs, and whether high cardiovascular risk could affect cardiac expres- sion ofKlotho, FGFs and other molecules. Methods We selected 20 patients with an estimated 10-year high atherosclerotic cardiovascular disease and 10 age-matched control subjects with an estimated 10-year low risk undergone cardiac surgery for reasons other than coronary artery by-pass. In myocardial biopsies, we evaluated by immuno-histochemistry whether Klotho and FGFs were expressed in cardiomyo- cytes, and whether higher cardiovascular risk influenced the expression of other molecules involved in endoplasmic reticulum stress, oxida- tive stress, inflammation and fibrosis. Results Only cardiomyocytes of patients with a higher cardiovascular risk showed lower expression of Klotho, but higher expressions of FGFs. Furthermore, higher cardiovascular risk was associated with increased expression of oxidative and endoplasmic reticular stress, inflammation and fibrosis. Conclusions This study showed for the first time that Klotho proteins are ex- pressed in human cardiomyocytes and that cardiac expression of Klotho is down-regulated in higher cardiovascular risk patients, while expression of stress-related molecules were significantly increased.

关键词： Atherosclerotic disease Cardiomyocytes Cardiovascular risk Human heart Klotho

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Dilemmas in end-stage heart failure

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Journal of Geriatric Cardiology 2015年第01期 57-65页

作者： Carol Chen-Scarabelli Louis Saravolatz Benjamin Hirsh pratik agrawal Tiziano M.Scarabelli Veterans Affairs Healthcare System Ann Arbor St.John Hospital and Medical Center/Wayne State University Zena and Michael A.Wiener Cardiovascular Institute Mount Sinai Medical CenterOne Gustave L.Levy Place

Heart failure(HF),a complex clinical syndrome due to structural or functional disorder of the heart,is a major global health issue,with a prevalence of over 5.8 million in the USA alone,and over 23 million *** a leading cause of hospitalizations among patients aged 65 years or older,HF is a major consumer of healthcare resources,creating a substantial strain on the healthcare *** paper discusses the epidemiology of HF,financial impact,and multifaccted predicaments in end-stage HF care.A search was conducted on the *** Library of Medicine website(***) using keywords such as end-stage heart failure,palliative care,ethical *** the poor prognosis of HF(worse than that for many cancers),many HF patients,caregivers,and clinicians arc unaware of the poor *** addition,the unpredictable clinical trajectory of HF complicates the planning of end-of-life care,such as palliative care and hospice,leading to underutilization of such *** conclusion,ethical dilemmas in end-stage HF are numerous,embroiling not only the patient,but also the caregiver,healthcare team,and society.

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Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease

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Journal of Geriatric Cardiology 2016年第08期 701-711页

作者： Giovanni Corsetti Evasio Pasini Tiziano M Scarabelli Claudia Romano pratik R agrawal Carol Chen-Scarabelli Richard Knight Louis Saravolatz Jagat Narula Mario Ferrari-Vivaldi Vincenzo Flati Deodato Assanelli Francesco S Dioguardi Department of Clinical & Experimental Sciences Division of Human Anatomy & PhysiopathologyUniversity of Brescia "S.Maugeri Foundation" IRCCSCardiology DivisionMedical Centre of Lumezzane Zena and Michael A Wiener Cardiovascular InstituteMount Sinai Medical Center Center for Heart and Vessel Preclinical Studies St.John Hospital & Medical CenterWayne State University School of Medicine VA Ann Arbor Health Care System University of Michigan Department of Cardiovascular Surgery "San Rocco" Hospital Department of Biotechnological and Applied Clinical Sciences University of L'Aquila Division of Sport-Internal Medicine Department of Clinical & Experimental SciencesUniversity of Brescia Department of Clinical Sciences and Community Health University of Milan

Background Klotho proteins(α-and β) are membrane-based circulating proteins that regulate cell metabolism,as well as the lifespan modulating activity of Fibroblast Growth Factors(FGFs).Recent data has shown that higher plasma circulating Klotho levels reduce cardiovascular risk,suggesting Klotho has a protective role in cardiovascular ***,although so far it has been identified in various organs,it is unknown whether cardiomyocytes express Klotho and FGFs,and whether high cardiovascular risk could affect cardiac expression of Klotho,FGFs and other *** We selected 20 patients with an estimated 10-year high atherosclerotic cardiovascular disease and 10 age-matched control subjects with an estimated 10-year low risk undergone cardiac surgery for reasons other than coronary artery *** myocardial biopsies,we evaluated by immuno-histochemistry whether Klotho and FGFs were expressed in cardiomyocytes,and whether higher cardiovascular risk influenced the expression of other molecules involved in endoplasmic reticulum stress,oxidative stress,inflammation and *** Only cardiomyocytes of patients with a higher cardiovascular risk showed lower expression of Klotho,but higher expressions of ***,higher cardiovascular risk was associated with increased expression of oxidative and endoplasmic reticular stress,inflammation and *** This study showed for the first time that Klotho proteins are expressed in human cardiomyocytes and that cardiac expression of Klotho is down-regulated in higher cardiovascular risk patients,while expression of stress-related molecules were significantly increased.

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Association between alcohol-associated cirrhosis and inpatient complications among COVID-19 patients:A propensity-matched analysis from the United

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World Journal of Virology 2023年第4期12卷 221-232页

作者： Faisal Inayat Hassam Ali pratik Patel Rubaid Dhillon Arslan Afzal Attiq Ur Rehman Muhammad Sohaib Afzal Laraib Zulfiqar Gul Nawaz Muhammad Hassan Naeem Goraya Subanandhini Subramanium Saurabh agrawal Sanjaya K Satapathy Department of Internal Medicine Allama Iqbal Medical CollegeLahore 54550PunjabPakistan Department of Internal Medicine East Carolina University Brody School of MedicineGreenvilleNC 27834United States Department of Gastroenterology Mather Hospital and Zucker School of Medicine at Hofstra UniversityPort JeffersonNY 11777United States Department of Gastroenterology Cleveland Clinic FoundationClevelandOH 44195United States Department of Hepatology Mercy Medical CenterBaltimoreMD 21202United States Department of Internal Medicine Louisiana State University HealthShreveportLA 71103United States Department of Internal Medicine Quaid-e-Azam Medical CollegeBahawalpur 63100PunjabPakistan Department of Hepatology Tampa General Medical Group and University of South FloridaTampaFL 33606United States Department of Hepatology North Shore University Hospital and Zucker School of Medicine at Hofstra UniversityManhassetNY 11030United States

BACKGROUND Alcohol-associated cirrhosis(AC)contributes to significant liver-related mortality in the United *** is known to cause immune dysfunction and coagulation *** with comorbid conditions like AC are at risk of worse clinical outcomes from coronavirus disease 2019(COVID-19).The specific association between AC and COVID-19 mortality remains inconclusive,given the lack of robust clinical evi-dence from prior *** To study the predictors of mortality and the outcomes of AC in patients hospitalized with COVID-19 in the United *** We conducted a retrospective cohort study using the National Inpatient Sample(NIS)database *** were identified with primary COVID-19 hospitalizations based on an underlying diagnosis of AC.A matched comparison cohort of COVID-19 patients without AC was identified after 1:N propensity score matching based on baseline sociodemographic characteristics and Elixhauser *** outcomes included median length of stay,median inpatient charges,and in-hospital *** outcomes included a prevalence of systemic *** A total of 1325 COVID-19 patients with AC were matched to 1135 patients without *** was no difference in median length of stay and hospital charges in COVID-19 patients with AC compared to non-AC(P>0.05).There was an increased prevalence of septic shock(5.7%vs 4.1%),ventricular fibrillation/ventricular flutter(0.4%vs 0%),atrial fibrillation(13.2%vs 8.8%),atrial flutter(8.7%vs 4.4%),first-degree atrioventricular nodal block(0.8%vs 0%),upper extremity venous thromboembolism(1.5%vs 0%),and variceal bleeding(3.8%vs 0%)in the AC cohort compared to the non-AC cohort(P<0.05).There was no difference in inpatient mortality in COVID-19 patients with non-AC compared to AC,with an odds ratio of 0.97(95%confidence interval:0.78-1.22,P=0.85).Predictors of mortality included advanced age,cardiac arrhythmias,coagulopathy,protein-calorie malnutrition,flui

关键词： Alcoholic cirrhosis COVID-19 Chronic liver disease Mortality predictors Inpatient complications

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