Therapeutics Commons^™

Outcomes Of Thoracic Endovascular Aortic Repair (Tevar) Procedure In Octogenarians, Nonagenarians And Centenarians: A Population-Based Study, Dakota B. Pastore, Tony Elias, Rafail Beshai, Kyrillos Girgis, Maziyar Daneshvar, Keith Anacker

Rowan-Virtua Research Day

Introduction: Limited data exists for patients undergoing a thoracic endovascular aortic repair (TEVAR) procedure who are older than or equal to 80 years old (YO). This study sought to examine the national inpatient sample (NIS) database to describe in-hospital outcomes among these older patients.

Methods: The NIS was searched for hospitalizations of adults who underwent a TEVAR procedure in 2019 and 2020. The study compared those aged 80 YO and over to those younger than 80 YO. The primary outcome was inpatient mortality. Secondary outcomes included hospital length of stay (LOS), and total hospital charges (TOTHCG).

Results: This study included …

Sex Differences In Outcomes Among Patients Undergoing Thoracic Endovascular Aortic Repair (Tevar) Procedure: A Retrospective Cohort Study, Dakota B. Pastore, Tony Elias, Rafail Beshai, Kyrillos Girgis, Maziyar Daneshvar, Keith Anacker

Rowan-Virtua Research Day

Introduction: There is limited data about sex differences in patients undergoing a thoracic endovascular aortic repair (TEVAR) procedure. This study sought to examine the national inpatient sample (NIS) database to describe in-hospital outcomes by gender.

Methods: The NIS was searched for hospitalizations of adult patients who underwent TEVAR in 2019 and 2020. For this cohort, female patients were identified, and pregnant patients were excluded. The primary outcome was inpatient mortality. Secondary outcomes included hospital length of stay (LOS), and total hospital charges (TOTHCG).

Results: This study included 696 patients who underwent TEVAR. 255 (36.6%) females were identified, of which, 7 …

Clinical Outcomes For Cardiac Ablation In Octogenarians, Nonagenarians, And Centenarians: A Retrospective Cohort Study, Tony Elias, Mena Elmalh, Kyrillos Girgis, Michael Valderrama, Rafail Beshai

Rowan-Virtua Research Day

Background

Cardiac ablation is a therapeutic intervention aimed at correcting abnormal heart rhythms by disrupting electrical pathways in the heart, using techniques such as radiofrequency or cryoablation. Despite its effectiveness, there is a scarcity of data regarding the outcomes of cardiac ablation specifically among elderly patients. Previous studies have highlighted the complexities and challenges associated with managing cardiac arrhythmias in the elderly population, emphasizing the need for further investigation into treatment outcomes in this demographic.1,2 Therefore, this study aimed to investigate in-hospital outcomes among elderly patients who underwent cardiac ablation using data from the National Inpatient Sample (NIS) Database.

Methods …

Sex Differences In Outcomes Among Patients Who Underwent Cardiac Ablation: A Retrospective Cohort Study, Tony Elias, Mena Elmalh, Kyrillos Girgis, Taha Syed, Rafail Beshai

Rowan-Virtua Research Day

Background Cardiac ablation, encompassing radiofrequency and cryoablation modalities, is a therapeutic intervention targeting abnormal heart rhythms by disrupting electrical pathways within the heart. Despite its widespread use, research focusing on sex-specific outcomes among patients undergoing cardiac ablation remains limited. Understanding potential sex differences in treatment response and outcomes is crucial for optimizing patient care and outcomes.1,2 Therefore, this retrospective cohort study aimed to analyze the national inpatient sample database to assess in-hospital outcomes among patients undergoing cardiac ablation, specifically focusing on sex disparities.

Methods Data from the National Inpatient Sample (NIS) Database for the years 2019 and 2020 were utilized …

National Inpatient Sample Analysis: Examining Clinical Outcomes In Cardiac Ablation Patients With Hyperlipidemia, Tony Elias, Mena Elmalh, Kyrillos Girgis, Taha Syed, Rafail Beshai

Rowan-Virtua Research Day

Background Cardiac ablation, utilizing radiofrequency or cryoablation, is a therapeutic approach for correcting abnormal heart rhythms by disrupting specific electrical pathways within the heart. Despite the growing utilization of cardiac ablation, limited research exists on the impact of hyperlipidemia, a prevalent cardiovascular risk factor, on outcomes in patients undergoing this procedure. Previous studies underscore the importance of understanding how comorbid conditions, such as hyperlipidemia, influence the efficacy and safety of cardiac ablation.1,2 Consequently, this study aimed to leverage the national inpatient sample database to investigate in-hospital outcomes among cardiac ablation patients with hyperlipidemia.

Methods Data from the National Inpatient Sample …

Use Of Point-Of-Care Ultrasound In The Diagnosis Of Postpartum Cardiomyopathy, Muhammad Noman, Frank A. Wheeler, James A. Espinosa, Alan Lucerna

Rowan-Virtua Research Day

Postpartum cardiomyopathy (PPCM), also known as peripartum cardiomyopathy is a rare form of heart failure (HF) that occurs in the late stages of pregnancy or in the early postpartum period. For it to be classified as PPCM, it must occur in the absence of another identifiable cause for HF and have left ventricular (LV) systolic dysfunction with an LV ejection fraction (LVEF) less than 45%. Here we present the case of a 46-year-old female G3P2 presented 5 days postpartum cesarean section delivery in acute respiratory distress where point of care ultrasound was used for assessment of the lungs to visualize …

Effects Of Obesity On Patients Undergoing Cardiomems Procedure: Retrospective Cohort Study, Tony Elias, Mena Elmalh, Priya Brahmbhatt, Kyrillos Girgis, Taha Syed, Michael Valderrama, Rafail Beshai

Rowan-Virtua Research Day

★ Remote hemodynamic monitoring (CardioMEMs) is becoming increasingly important for management of chronic heart failure patients.

★ There is limited data looking specifically for obese patients who undergo CardioMEMs implantation.

★ We sought to examine the national inpatient sample database to describe in-hospital outcomes for this demographic

Potential Mechanisms For New Onset Atrial Fibrillation In Covid-19 Patients, Raghav Gupta, Yara Assadi, Shaniece Nicole Lawrence, Erika Jeanie Pitsker, Michael Scott Bickford Jr., Victoria Amber Saniko

Rowan-Virtua Research Day

Introduction: This study shows the prevalence of New-Onset Atrial Fibrillation in COVID-19 patients and highlights the most prevalent explanatory pathologic theories for the correlation.

Methods: The authors carried out a literature review over PubMed using the keywords “atrial fibrillation” and “long-term COVID.” 48 articles were reviewed. Articles relating to new onset of atrial fibrillation in COVID-19 patients were included while articles posted before 2020, not related to COVID and atrial fibrillation were excluded.

Results: The prevalence of atrial fibrillation in COVID patients is often reported to be around 17%, however 44% of patients within Intensive Care units (ICU) have atrial …

Case Report: Overdrive Pacing In Refractory Ventricular Tachycardia, Alyssa A. Baldini, Kishan B. Patel

Rowan-Virtua Research Day

We report a case of a 67-year-old male who presented to the emergency department (ED) for palpitations and complaint of his automated implantable cardioverter defibrillator (AICD) firing at home who had multiple episodes of persistent ventricular tachycardia (VT) during his course of stay in the ED. Patients with pacemakers and AICDs can present an additional layer of complexity when treating these conditions. Temporary overdrive pacing (TOP) should be considered as a treatment to correct refractory ventricular tachycardia in patients with implanted pacemakers and AICDs presenting to the ED.

Atypical Case Of Recurrent Saddle Pulmonary Embolism With Associated Chronic Hypoxia, Karl Schlicht

Rowan-Virtua Research Day

A saddle pulmonary Embolism (PE) represents a blood clot within the pulmonary artery vasculature that lodges itself between both the left and right pulmonary artery. They can be described as being massive or sub-massive. Massive PE’s cause large clot burden that puts the patient risk for sudden hemodynamic collapse, while sub-massive saddle PE’s typically do not cause hemodynamic collapse nor significant cardiac effects, such as right heart dysfunction. As clinicians, we need to be vigilant about whether a patient is placed into that criteria of sub-massive or massive and act quickly to start management that could be lifesaving.

“Lupus, Marijuana, And Takotsubo: A Perfect Storm”: An Unusual Presentation Of Takotsubo Cardiomyopathy, Matthew Orap, Parth Patel, Haitham Dib

Rowan-Virtua Research Day

Takotsubo cardiomyopathy is a type of myocardial injury that is marked with left ventricular contraction dysfunction. Various regions of the left ventricular wall may exhibit hypokinetic or hypercontractile activity. There is no exact mechanism elucidated for Takotsubo cardiomyopathy, but it is often associated with a triggering stressful event that leads to a catecholamine surge. We describe a 38-year-old female who presented with typical Takotsubo cardiomyopathy, likely in the setting of worsening systemic lupus erythematosus (SLE) exacerbations and excessive cannabis use. The patient described her pain as a tight burning sensation that started on her right side and traveled to the …

Clinical Outcomes For Impella Patients Associated With Hyperlipidemia: An Analysis Of The National Inpatient Sample, Tony Elias, Sonika Vatsa, Kyrillos Girgis, Taha Syed, Rafail Beshai

Rowan-Virtua Research Day

The Impella, a ventricular assist device, is crucial for managing severe heart failure and cardiogenic shock. Despite its widespread use, there's scant information on how hyperlipidemia affects Impella patients. To address this gap, we delved into the National Inpatient Sample Database from 2019 and 2020. Our aim was to scrutinize in-hospital outcomes among these patients. We identified 8233 Impella patients, among whom 1012 (12.3%) had hyperlipidemia. Those with hyperlipidemia displayed higher rates of hypertension, diabetes mellitus, and chronic kidney disease compared to their counterparts without hyperlipidemia. Shockingly, in-hospital mortality was notably elevated in the hyperlipidemia group, emphasizing its clinical significance. …

Education Of The Effects Of Obesity Medications And A Stepwise Approach To Mitigate Prevalence And Encourage Lifestyle Medicine For Primary Care Physicians, Kiely M. Curran

Department of Nutrition Student Projects

My Capstone project is an Educational Manual that emphasizes a healthcare team approach to the treatment and management of obesity. The Educational Manual consists of a standardized protocol in management of obesity in patients and a document with summarized references for primary care providers; and a simplified document for patient education. There is a growing interest in the usage of obesity medications. The purpose of my Capstone project is to provide a simplified manual for the primary care provider to reference to make knowledgeable and patient-centered decisions in the prescription of obesity medications and decisions in weight-management. My methodology included …

Aortic Stenosis Management In Patients With Acute Hip Fracture, Juan A. Terré, Juan Torrado, Isaac George, Rafael Harari, Pedro R. Cox-Alomar, Pedro A. Villablanca, Robert T. Faillace, Juan F. Granada, George Dangas, Mario J. Garcia, Azeem Latib, José Wiley

School of Medicine Faculty Publications

The treatment of severe aortic stenosis (SAS) has evolved rapidly with the advent of minimally invasive structural heart interventions. Transcatheter aortic valve replacement has allowed patients to undergo definitive SAS treatment achieving faster recovery rates compared to valve surgery. Not infrequently, patients are admitted/diagnosed with SAS after a fall associated with a hip fracture (HFx). While urgent orthopedic surgery is key to reduce disability and mortality, untreated SAS increases the perioperative risk and precludes physical recovery. There is no consensus on what the best strategy is either hip correction under hemodynamic monitoring followed by valve replacement or preoperative balloon aortic …

Efektivitas Sacubitril/Valsartan Dalam Mencegah Gagal Jantung Pada Stemi Pasca Percutaneous Coronary Intervention, Nobian Andre, Lana Adila, Aulia Rizka, Lusiani Rusdi

Jurnal Penyakit Dalam Indonesia

Heart failure is a possible complication following ST-elevation myocardial infarction (STEMI) even after revascularization. Neuroendocrine activation in the process of ventricular remodeling can be regulated by angiotensin receptor-neprilysin inhibitor (ARNI) as well as angiotensin-converting enzyme (ACE) inhibitor. The use of ARNI in heart failure with reduced ejection fraction has been found to be superior to ACE inhibitor. The role of ARNI on cardiac function in STEMI has not been established. A clinician treating a patient with STEMI considered giving sacubitril/valsartan to reduce the risk of developing heart failure. Literature search was performed in three electronic databases: PubMed, Embase, and Cochrane. …

Using Noninvasive Calibrated Cuff Plethysmography To Observe The Effects Of Cold-Water Immersion On Arterial Compliance, Rita M. Grigorian

Biomedical Engineering: Graduate Reports and Projects

As the prevalence of cardiovascular diseases continues to exponentially grow in populations across the globe, the necessity of determining underlying factors, effective methods of diagnoses, and universally available preventive measures also grows. Early detection of endothelial dysfunction, a proven precursor of cardiovascular diseases, can be extremely impactful in encouraging preventative measures and early intervention before medical conditions become chronic. In recent years, ice plunging, a form of cryotherapy involving full body immersion in cold water, has gained popularity within circles of fitness and health practitioners, gaining the interest of people of all backgrounds. Certain parallels observed between the human physiological …

Social Determinants May Limit The Success Of Pcsk9 Inhibitors, An Effective Treatment For Hyperlipidemia In Statin-Intolerant Patients, Abigail C. Kuplicki

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Moriarty PM, Thompson PD, Cannon CP, et al. Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: The ODYSSEY ALTERNATIVE randomized trial. J. Clin. Lipidol. 2015;9(6):758-769. https://doi.org/10.1016/j.jacl.2015.08.006

for a statin-intolerant patient with hyperlipidemia.

Persistent Increase In Serum Ferritin Levels Despite Converting To Permanent Vascular Access In Pediatric Hemodialysis Patients: Pediatric Nephrology Research Consortium Study, Ali Mirza Onder, Md Abu Yusuf Ansari, Fang Deng, Matthew M. Grinsell, Larry Patterson, Jennifer Jetton, Sahar Fathallah-Shaykh, Daniel Ranch, Diego Aviles, Lawrence Copelovitch, Eileen Ellis, Vimal Chadha, Ayah Elmaghrabi, Jen-Jar Lin, Lavjay Butani, Maha Haddad, Olivera Marsenic, Paul Brakeman, Raymond Quigley, H Stella Shin, Rouba Garro, Rupesh Raina, Craig B. Langman

School of Medicine Faculty Publications

Our objective was to examine serum ferritin trends after conversion to permanent vascular access (PVA) among children who started hemodialysis (HD) using tunneled cuffed catheters (TCC). Retrospective chart reviews were completed on 98 subjects from 20 pediatric HD centers. Serum ferritin levels were collected at the creation of PVA and for two years thereafter. There were 11 (11%) arteriovenous grafts (AVG) and 87 (89%) arteriovenous fistulae (AVF). Their mean TCC use was 10.4 ± 17.3 months. Serum ferritin at PVA creation was elevated at 562.64 ± 492.34 ng/mL, increased to 753.84 ± 561.54 ng/mL (p = < 0.001) in the first year and remained at 759.60 ± 528.11 ng/mL in the second year (p = 0.004). The serum ferritin levels did not show a statistically significant linear association with respective serum hematocrit values. In a multiple linear regression model, there were three predictors of serum ferritin during the first year of follow-up: steroid-resistant nephrotic syndrome as primary etiology (p = 0.035), being from a center that enrolled >10 cases (p = …

Mixed Beri’S: High Output Heart Failure From Severe Anemia And Thiamine Deficiency, Rohan Umrani, Hiral Amin, Ashley Pinckney, Charles Yang, Daniel Tran

Rowan-Virtua Research Day

Background: Severe anemia and thiamine deficiency can independently result in high output heart failure (HOHF) through different mechanisms. Data on the threshold and timeframe at which these etiologies may precipitate HOHF is unclear.

Case: A 63-year-old male with alcohol use disorder consuming 18 drinks/week presented with progressive shortness of breath and lower extremity edema for a few months. Physical exam revealed tachycardia, anasarca, jugular venous distension, Lancisi’s sign, and a midsystolic murmur. Echocardiogram demonstrated EF of 30-35%, dilated left ventricle, and cardiac index of 4.2L/min/m2.

Decision-Making: Heart failure can independently precipitate anemia while severe alcoholism can induce myelosuppression and promote …

Dislodged Endovascular Heat-Induced Thrombus Resulting In Pulmonary Embolus Following Post-Operative Ultrasound Compression, Danielle Park, Aghilas Belkadi, Luke Perry, Michael Kachmar, Holly Graves

Rowan-Virtua Research Day

Introduction: Venous insufficiency and consequent varicose veins are common problems faced by many patients. Fortunately, there are many treatment options available including a minimally invasive method known as radiofrequency ablation (RFA). RFA is not without complications; amongst those are endovascular heat induced thrombosis (EHIT). This rare complication is typically managed conservatively; however, in rare occasions, the thrombus can detach and embolize causing further issues for patients.

Case Description: A 48-year-old male underwent an uneventful RFA procedure for a CEAP 4a venous insufficiency. On the post-operative ultrasound venous duplex evaluation, the patient was found to have EHIT type 2 in the …

Chewed Versus Swallowed Ticagrelor In P2y12 Inhibitor-Naïve Patients Undergoing Percutaneous Coronary Intervention, Thomas F. Wilson, Muddasir Ashraf, M. Fuad Jan, Tonga Nfor, Louie Kostopoulos, Joaquin Solis, Jayant Khitha, Ahmad Khraisat, Anthony C. Defranco, Tanvir Bajwa, Suhail Q. Allaqaband

Journal of Patient-Centered Research and Reviews

Purpose: Dual antiplatelet therapy is standard for patients undergoing percutaneous coronary intervention (PCI) with stents. Traditionally, patients swallow the loading dose of a P2Y12 inhibitor before or during PCI. Time to achieve adequate platelet inhibition after swallowing the loading dose varies significantly. Chewed tablets may allow more rapid inhibition of platelet aggregation. However, data for this strategy in patients with stable ischemic heart disease or non-ST-elevation acute coronary syndrome (NSTE-ACS) are less robust.

Methods: In this single-center prospective trial, 112 P2Y12-naïve patients with stable ischemic heart disease or NSTE-ACS on aspirin therapy and who received ticagrelor after coronary angiography but …

A Design, Development, And Evaluation Of Bio-Patch For Myocardial Tissue Repair, Yaya Zhang

Theses and Dissertations (ETD)

Introduction. Ischemic heart disease (IHD) is a major concern of human health issue. The structural repair and functional recovery of injured hearts is a major challenge in the clinical setting. Preclinical studies over last 10 years have demonstrated the potential of using stem cells to treat IHD, but the efficacy of this therapy is jeopardized by uncontrollable migration and low survival of the injected stem cells. An approach based on tissue engineering enabling target-specific stem cell delivery such as cardiac patches has emerged as an alternative solution for stem cell therapy for IHD. It employs scaffold materials to engulf various …

Prevention Of Doxorubicin-Induced Cardiotoxicity By A Coumestan Analogue, Psoralidin, Mujtaba H. Shah, Myia Aiges, Kota V. Ramana

Annual Research Symposium

Natural phenolic compound Psoralidin limits cardiotoxicity associated with Doxorubicin

A Brief Literature Review On Heparin: To Bolus Or Not To Bolus, That Is The Question, Alex Gechlik, James Espinosa, Alan Lucerna, Kishan Patel

Rowan-Virtua Research Day

Heparin is an anticoagulant medication, used to inhibit the formation of thrombi that pose arteriolar and vein-occlusive risk. The choice between starting a heparin infusion with or without an initial bolus is case dependent based on whether a patient is already anticoagulated and if so, foregoing an initial bolus. In contrast, both anticoagulated and non-anticoagulated patients share the same goal when receiving Heparin for various thromboembolic syndromes, and that is to be within aPTT target range of 1.5-2.5 or 45 to 75 seconds. Falling below goal range leads to a 20-25% recurrence of VTE, and aPTT above goal range has …

Reducing 30 Day Chf Readmission Rates: Evaluating Medication Efficacy, Jesse Bebout Msn, Rn, Ccrn, Brandon May Bsn, Rn, Tiara Richmond Bsn, Rn, Margaret Harvey Phd, Aprn, Acnp-Bc, Chfn

Doctor of Nursing Practice Projects

Purpose/Background Heart failure (HF) is a leading cause of hospital readmissions and lost revenue under the Hospital Readmission Reduction Program (HRRP). Medication management plays a crucial role in controlling HF symptoms leading to hospitalization. This scoping review examines the benefits of angiotensin receptor-neprilysin inhibitors versus beta-blockers in reducing hospital readmissions within 30 days of discharge related to heart failure with reduced ejection fraction (HFrEF) in the United States.

Methods We conducted a literature search from August 2020 to November 2021 on the Google Scholar, PubMed, and CINAHL databases using the key phrases heart failure with reduced ejection, beta-blockers, angiotensin receptor-neprilysin …

A Case Of Protein Losing Enteropathy After Fontan Operation, Gina Kim

Capstone Showcase

Protein Losing Enteropathy (PLE) is a condition in which an excessive amount of proteins are lost through the gastrointestinal tract leading to hypoproteinemia and manifesting as edema, ascites, and diarrhea. While in most cases PLE is a treatable disorder with good outcomes, the morbidity and mortality of the disorder is significantly elevated in patients with a history of Fontan surgery–an operation used to palliate patients born with a single ventricle by rerouting venous blood return directly to pulmonary circulation. After failure of first-line therapeutics of diuretics and steroids, this case study explores the successful treatment of a 5-year-old patient with …

(De)Constructing ‘Therapeutic Itineraries’ Of Hypertension Care: A Qualitative Study In The Philippines, Jhaki A. Mendoza, Gideon Lasco, Alicia Renedo, Lia M. Palileo-Villanueva, Maureen L. Seguin, Benjamin Palafox, Arianna Maever L. Amit, Veincent Christian F. Pepito, Martin Mckee, Dina Balabanova

Development Studies Faculty Publications

Hypertension, a major risk factor for non-communicable diseases, remains poorly controlled in many countries. In the Philippines, it is still one of the leading causes of preventable deaths despite the accessibility and availability of essential technologies and medicine to detect and treat hypertension. This paper characterizes the ‘therapeutic itineraries’ of people with hypertension from poor communities in rural and urban settings in the Philippines. We employ longitudinal qualitative methodology comprised of repeat interviews and digital diaries using mobile phones from 40 recruited participants in 12 months. Our findings demonstrate that therapeutic itineraries, rather than being organized according to categories that …

Near-Field Electrospinning And Characterization Of Biodegradable Small Diameter Vascular Grafts, William E. King Iii

Theses and Dissertations (ETD)

The ideal “off the shelf” tissue engineering, small-diameter (< 6 mm inner diameter (ID)) vascular graft hinges on designing a template that facilitates transmural ingrowth of capillaries to regenerate an endothelized neointimal surface. Previous traditionally electrospun (TES) approaches to create bioresorbable vascular grafts lack the pore sizes required to facilitate transmural capillary ingrowth required for successful in situ neovascular regeneration. Therefore, the ability to create scaffolds with program-specific architectures independent of fiber diameter via the relatively recent sub-technique of near-field electrospinning (NFES) represents a promising solution to create tissue engineering vascular grafts. These programmed large pore sizes are anticipated to promote in situ regeneration and improve the outcomes as well as the quality of life of patients with arterial disease.

In this dissertation, we manufactured via NFES as well as characterized biodegradable polydioxanone (PDO) small-diameter vascular grafts. Chapter 1 introduces the need for off-the-shelf, small-diameter vascular grafts to facilitate in situ regeneration, the process and pore size limitations of TES vascular grafts, and the promising use of NFES to develop precisely tailored PDO vascular grafts. Chapter 2 describes the process of NFES and details the current progress in NFES of biomedical polymers as well as the major limitations that exist in the field. Chapters 3, 4, and 5 contain primary research …

C25: The “Spot Sign”: A Predictor Of Hematoma Expansion, Mckenzie Merritt

Annual Research Symposium

No abstract provided.

Nanomaterials As Novel Cardiovascular Theranostics, Rajasekharreddy Pala, Subhaswaraj Pattnaik, Siddhardha Busi, Surya M. Nauli

Pharmacy Faculty Articles and Research

Cardiovascular diseases (CVDs) are a group of conditions associated with heart and blood vessels and are considered the leading cause of death globally. Coronary heart disease, atherosclerosis, myocardial infarction represents the CVDs. Since CVDs are associated with a series of pathophysiological conditions with an alarming mortality and morbidity rate, early diagnosis and appropriate therapeutic approaches are critical for saving patients’ lives. Conventionally, diagnostic tools are employed to detect disease conditions, whereas therapeutic drug candidates are administered to mitigate diseases. However, the advent of nanotechnological platforms has revolutionized the current understanding of pathophysiology and therapeutic measures. The concept of combinatorial therapy …