Hasitha Manohar | Loyola University Chicago (original) (raw)

Papers by Hasitha Manohar

Perspectives in Clinical Research, 2015

Study period and study population The study was conducted from March, 2012 to August, 2012. The p... more Study period and study population The study was conducted from March, 2012 to August, 2012. The patients admitted in the department of Radiotherapy and treated with anti-neoplastic drugs during the study period were included in the present study.

Journal of the American College of Cardiology, May 1, 2021

Objective: To identify in the literature the cardiovascular adverse events resulting from oral an... more Objective: To identify in the literature the cardiovascular adverse events resulting from oral antineoplastic therapy. Method: Integrative review of the literature through the SCOPUS, Scientifi c Electronic Library Online (SciELO), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medical Literature Analysis and Retrieval System Online (MEDLINE) databases. The antineoplastic, cardiotoxicity, cardiovascular system and adverse reaction descriptors were used in Portuguese, English and Spanish. We selected 23 articles published between 1985 and 2015. Results: Twenty studies were related to cardiac events and eleven to peripheral vascular events. The most frequent adverse cardiac events were reduced left ventricular ejection fraction, myocardial infarction, changes in the electrocardiogram, heart failure and angina, whereas peripheral vascular events were hypertension and thromboembolism. Conclusion: Oral antineoplastic therapy is associated with different adverse events, including cardiac and peripheral vascular events.

Circulation

Introduction: Aortic stenosis (AS) is one of the most prevalent valvular heart diseases globally.... more Introduction: Aortic stenosis (AS) is one of the most prevalent valvular heart diseases globally. As many as 16% of AS patients have underlying cardiac amyloidosis (CA). To date, there is a paucity of data on outcomes among AS with concomitant CA patients post-TAVR. Hypothesis: This study aimed to evaluate the clinical outcomes post TAVR among patients with CA. Methods: We performed a systematic literature search of databases for relevant articles from inception until June 01, 2022. Unadjusted odds ratios (OR) were pooled using a random-effect model, and a p-value of <0.05 was considered statistically significant. Results: 5 studies with 1,488 patients were involved in the final analysis. The mean age of patients among CA+AS and AS alone was (85 vs 80) years. The number of males affected with dual pathology was higher compared to AS alone (71% vs 59%). 29% of patients were having a right bundle branch block in the CA+AS group, while 12% were among AS alone. Mean IV Septal Thickne...

Circulation

Background: Surgical myectomy (SM) and Alcohol septal ablation (ASA) are two known therapies reco... more Background: Surgical myectomy (SM) and Alcohol septal ablation (ASA) are two known therapies recommended for symptomatic hypertrophic cardiomyopathy patients. Although, their results are contradictory between the outcomes of these two procedures to this day. Hypothesis: This meta-analysis evaluates and compares the two procedure-related clinical outcomes. Method: We performed a systematic literature search on PubMed, Embase and Cochrane for relevant articles from inception until May 20, 2022. Unadjusted odds ratios (OR) were pooled using a random-effect model, and a p-value of <0.05 was considered statistically significant. Result: A total of 23 articles with 17165 patients comparing the outcomes among SM vs ASA with a mean follow-up of 44.18±24.06 months. The odds of short-term mortality [OR, 0.51(95%CI: 0.33-0.79), p = 0.002] were significantly lower in ASA group, while reintervention [OR, 2.93 (95%CI: 0.99-8.70), p = 0.05], and pacemaker implantation [OR, 1.97(95%CI: 1.28-3.03...

Healthcare, Dec 2, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Current Atherosclerosis Reports

Purpose of Review: The review focuses on the shared risk factors observed between coronary heart ... more Purpose of Review: The review focuses on the shared risk factors observed between coronary heart disease and cancer, cancer therapeutics causing coronary heart disease, and potential strategies to mitigate atherosclerosis in patients with cancer. Recent Findings: The pathophysiology behind how traditional cardiovascular risk factors also contribute to cancer development and mortality is increasingly recognized. In addition, newer cancer therapies, such as immune checkpoint inhibitors, cause increased inflammation leading to increased cardiovascular events. Summary: Traditional coronary heart disease risk factors such as obesity, hypertension, diabetes, and hyperlipidemia also contribute to cancer development and worse cancer outcomes. Cancer therapeutics can also lead to atherosclerotic events in addition to the shared risk factors present at the time of cancer diagnosis. Understanding the pathophysiology, using multidisciplinary care teams, and developing machine learning algorithms for individualized patient care will help to mitigate the risk of coronary heart disease in patients with cancer.

International Journal of Applied and Basic Medical Research

With the recent increase in clinical trials, lower- and middle-income countries are preferred tri... more With the recent increase in clinical trials, lower- and middle-income countries are preferred trial sites due to lower budgets and easy availability of potential participants. On trial completion, benefits to participants cease and it may affect their health adversely. Therefore, entitlement to posttrial access (PTA) of interventions is imperative. The Declaration of Helsinki and several other guidelines mandate that trial participants have access to experimentally proven efficacious drugs and that the research protocol should mention PTA provision mechanisms. A controversial question about PTA is whether, experimentally proven therapy should be made accessible to the control group as well as the community from which the participants were enrolled, especially if no satisfactory standard treatment exists. PTA has significant implications for various stakeholders – trial participants, investigators, sponsors, regulatory authorities, and governments and has been discussed and well addressed in recent guidelines issued by the Indian Council of Medical research. This article focuses on the PTA, guidelines related to PTA, disputes, different stakeholder perspectives, and practical difficulties in its implementation. It also looks at PTA from the Indian perspective and considers possible solutions to deal with the controversies.

Circulation

Introduction: COVID-19 infection is associated with troponin elevation, which is associated with ... more Introduction: COVID-19 infection is associated with troponin elevation, which is associated with increased mortality. We wanted to evaluate whether troponin levels, GRACE scores, and TIMI scores were independently associated with mortality in COVID-19 patients. Methods: Out of 1500 COVID-19 patients admitted to our hospitals, 217 patients with troponin levels were included. Key variables were collected manually, and survival analysis was done. Results: Mortality was 26.5% in the normal troponin group and 54.6% in the elevated troponin group. Patients with elevated troponins had increased frequency of hypotension (P=0.01), oxygen support (P<0.01), low absolute lymphocyte count (P<0.01), elevated blood urea nitrogen (P<0.01), higher C-reactive protein (P<0.01), higher D-dimer (P<0.01), higher lactic acid (P<0.01), and higher qSOFA, SOFA, TIMI, and GRACE scores (all scores P<0.01). On cox regression, troponin elevation (HR 1.85, 95% CI 1.18-2.88, P<0.01), TIMI s...

Caesalpinia Pulcherrima is commonly known as a Peacock’s pride. Plant is enriched with flavonoids... more Caesalpinia Pulcherrima is commonly known as a Peacock’s pride. Plant is enriched with flavonoids, triterpenoids, tannins and phenolic compounds. Wound healing process is complex, and involves many cellular intermediate pathways. Two models were adopted to evaluate the wound healing activity of Caesalpinia pulcherrima (Stem bark): excision and incision wound model in wistar rats. Hydroalcoholic extract of C. pulcherrima (stem bark) was incorporated in to the lipophilic base ointment to achieve the 10 and 20% w/w concentration. In excision and incision skin wound models, herbal medicated ointment formulation was applied topically for 21 days and 10 days respectively after the induction of wound injury. In excision wound model, high dose (20% w/w) of ointment was found to be more statistically significant (p<0.05) and (p<0.001) on wound contraction on 7th and 14thday respectively when compared to the control group. Low dose (10% w/w) group was significant (p<0.05) but less si...

American Journal of Gastroenterology, 2021

Introduction: Vaccine-associated autoimmunity is a well-known phenomenon attributed to either the... more Introduction: Vaccine-associated autoimmunity is a well-known phenomenon attributed to either the cross-reactivity between antigens or the effect of adjuvant. The reactogenicity of COVID-19 mRNA vaccine in individuals suffering from immune-mediated diseases has not been investigated. We would like to present a case of Crohn's disease flare up after receiving COVID-19 Pfizer vaccine. Case description/methods: 33 years old male with history of Crohn's Disease (CD) complicated by fistula formation s/p Right hemicolectomy with ileocolic anastomosis in 2014 was admitted due to abdominal pain, diarrhea and rectal bleeding for 2 days. Patient reported he did not have any CD symptoms and was off maintenance medications therapy for 1.5 years. He had first dose of COVID Pfizer vaccine 2 days before his symptoms have started. Physical examination was significant for tenderness in RLQ, vitals were stable and patient afebrile. A laboratory work up was significant for elevated ESR (22), iron deficient anemia, B12 deficiency, hypophosphatemia and hypomagnesemia. Stool studies were negative for signs of infection Abdominal and Pelvic CT scan with contrast shown stable enlarged mesenteric lymph nodes and no signs of acute inflamatory process.Colonoscopy showed Rutgeerts score i1 and no evidence of of colonic CD involvement. Colonoscopy also revealed active inflammation, ulceration and adenomatous change at ileocolic anastomosis. Patient was consulted with Gastroenterology and treated with Prednisone 40 mg, IV Iron, B12 and electrolytes with rapid improvement of patient's symptoms. Discussion: During the past decades, there has been growing awareness of possible adverse events associated with vaccinations. When coming to COVID-19 vaccine, it is further complicated by the nucleic acid formulation and the accelerated development process imposed by the emergency pandemic situation. Currently formulated mRNA vaccines coding for the SARS-CoV-2 full-length spike protein have shown the highest level of evidence according to the efficacy and safety profile in clinical trials. Although the results from phase I and II/III studies have not raised serious safety concerns, patients with underlying immune-mediated disease were not specifically studied. mRNA vaccines may give rise to a cascade of immunological events eventually leading to the aberrant activation of the innate and acquired immune system that can be potentially associated with exacerbation of conditions involving dysregulated immune responses such as Crohn's disease.

Journal of Cellular Biochemistry, 2021

The co‐chaperone Bcl2‐associated athanogene‐3 (BAG3) maintains cellular protein quality control t... more The co‐chaperone Bcl2‐associated athanogene‐3 (BAG3) maintains cellular protein quality control through the regulation of heat shock protein 70 (HSP70). Cancer cells manipulate BAG3‐HSP70‐regulated pathways for tumor initiation and proliferation, which has led to the development of promising small molecule therapies, such as JG‐98, which inhibit the BAG3‐HSP70 interaction and mitigate tumor growth. However, it is not known how these broad therapies impact cardiomyocytes, where the BAG3‐HSP70 complex is a key regulator of protein turnover and contractility. Here, we show that JG‐98 exposure is toxic in neonatal rat ventricular myocytes (NRVMs). Using immunofluorescence microscopy to assess cell death, we found that apoptosis increased in NRVMs treated with JG‐98 doses as low as 10 nM. JG‐98 treatment also reduced autophagy flux and altered expression of BAG3 and several binding partners involved in BAG3‐dependent autophagy, including SYNPO2 and HSPB8. We next assessed protein half‐life with disruption of the BAG3‐HSP70 complex by treating with JG‐98 in the presence of cycloheximide and found BAG3, HSPB5, and HSPB8 half‐lives were reduced, indicating that complex formation with HSP70 is important for their stability. Next, we assessed sarcomere structure using super‐resolution microscopy and found that disrupting the interaction with HSP70 leads to sarcomere structural disintegration. To determine whether the effects of JG‐98 could be mitigated by pharmacological autophagy induction, we cotreated NRVMs with rapamycin, which partially reduced the extent of apoptosis and sarcomere disarray. Finally, we investigated whether the effects of JG‐98 extended to skeletal myocytes using C2C12 myotubes and found again increased apoptosis and reduced autophagic flux. Together, our data suggest that nonspecific targeting of the BAG3‐HSP70 complex to treat cancer may be detrimental for cardiac and skeletal myocytes.

Research Journal of Pharmacy and Technology, 2016

The objective of the current study is evaluate the cardioprotective activity of ethanolic fruit e... more The objective of the current study is evaluate the cardioprotective activity of ethanolic fruit extract of Limonia acidissima against isoproterenol induced myocardial infarction in rats. The protective activity of Limonia acidissima was assessed by estimating the cardiac marker enzymes (Creatinine Phosphokinase and Lactate Dehydrogenase) and antioxidants enzymes (superoxide dismutase and Catalase). Thirty male Sprague-Dawley rats (180–220 gm) were randomly allocated in 5 groups of 6 each. Group I served as control, II to V animals were Isoproterenol (85mg/kg) induced myocardiaol infracted animals, pre treated with the reference control Lipistat (350mg/kg) and ethanolic fruit extract of Limonia acidissima (200 and 400 mg/kg). All the test drugs were administered orally for 15 days. On 16th day the blood was collected and subjected to the estimation of cardiac marker enzymes. The animals were sacrificed; hearts were homogenized and used for the estimation of antioxidant enzymes. The result shows that, Limonia acidissima significantly decreased the cardiac marker enzyme and increased the antioxidant enzymes. Limonia acidissima produced a dose dependent cardioprotective effect against the acute cardiac damage induced by Isoproterenol in rats. From the result it was concluded that, Limonia acidissima produced cardioprotective activity against isoproterenol induced cardiac damage in rats which was mediated by its antioxidant property.

Journal of the American College of Cardiology, 2018

Background: Prosthetic valve thrombosis events are estimated to occur between 0.03% and 0.13% per... more Background: Prosthetic valve thrombosis events are estimated to occur between 0.03% and 0.13% per patient-year. Some patients with this complication are unable to undergo surgical management, and are not candidates for thrombolytic therapy. Case: A 46-year-old morbidly obese (BMI 71.9 kg/m2) woman presented with a 4-week history of increased shortness of breath, as well as a 40-pound weight gain and worsening renal function. She had a history of a mitral valve replacement with a mechanical prosthesis, performed 8 months prior to this presentation. Transthoracic echocardiogram showed a markedly reduced left ventricular systolic function (left ventricular ejection fraction <20%, LV end diastolic dimension 7.6cm) as well as increased trans-mitral gradients (peak 14 mmHg, mean 9 mmHg) and a severely dilated left atrium. Right heart catheterization subsequently demonstrated severely elevated left and right filling pressures (right atrial pressure 39 mmHg, pulmonary artery pressure 67/48 mmHg, and pulmonary capillary wedge pressure 48mmHg). Fluoroscopy of the mitral valve prosthesis demonstrated a single frozen leaflet and normal range of motion of the other leaflet. Decision-making: Considering her morbid obesity and desire to avoid a repeat sternotomy, a novel percutaneous approach to free the frozen leaflet was attempted. Using a transseptal approach and an Agilis sheath, an Amplatz Super Stiff wire was advanced to the left atrium and used to repeatedly tap the frozen leaflet until mobility was restored. Post procedurally, she had no focal neurological deficits, embolic manifestations or bleeding complications. Trans-esophageal echocardiography confirmed normal range of motion of both prosthetic valve leaflets, and restoration of normal trans-mitral gradients Conclusion: Percutaneous manipulation of prosthetic valve may be a feasible option when thrombolytic or redo surgery is not possible. Larger trials need to be done to further confirm the safety and effectiveness of this procedure and further define patient subgroups who would benefit the most from this novel approach.

Indian journal of pharmacology

The aim of the study was to analyze the adverse drug reaction (ADR) profile of microtubule-damagi... more The aim of the study was to analyze the adverse drug reaction (ADR) profile of microtubule-damaging antineoplastic drugs (taxanes and vinca alkaloids) and to look for unexpected ADRs among the local population. Focused study on these drugs, rampantly used in oncology department for a wide variety of tumors including early and advanced malignancies, would enable better treatment care by physicians. Data on ADRs were collected from the cancer patients belonging to both gender and of all ages, on taxanes- or vinca-based cancer chemotherapy and reported in the Indian Pharmacopoeia Commission form. Causality was assessed using the WHO criteria and Naranjo's Algorithm. Preventability and severity of ADRs were also assessed. A total of 97 ADRs were reported among 488 patients on microtubule-damaging anticancer drugs admitted over a period of 1 year. The incidence rate was 19.87%. Gastrointestinal system (40.2%) was the most affected followed by bone marrow (33%) and skin (8.2%). The hi...

International Journal of Basic and Clinical Pharmacology, 2016

Background: Human immunodeficiency virus (HIV) presently accounts for the highest number of death... more Background: Human immunodeficiency virus (HIV) presently accounts for the highest number of deaths due to any infective agent in the world. The present study assessed the one year treatment outcome following antiretroviral therapy in HIV positive, treatment naïve patients in a tertiary care hospital. Methods: Adult HIV positive, antiretroviral treatment naive patients who were started on antiretroviral therapy (ART) between 1 st January 2011 and 31 st May 2013 were included in the study. Data was collected from their case records. CD4+cell count, haemoglobin level, weight, occurrence of opportunistic infections (OIs) and adverse drug reactions (ADRs) were analysed at baseline, 6 and 12 months following start of antiretroviral therapy. Data was analysed using parametric and nonparametric tests. Results: Data of 325 patients was analysed. Overall, the median increase in CD 4 + count at 1 year after initiation of treatment was observed to be clinically significant. Patients on tenofovir based regimen showed a significantly greater increase in the median CD 4 + count (P = 1.12×10-05) and haemoglobin (P = 0.002) as compared to those on non-tenofovir based regimen. A total of 151 ADRs were recorded in the study, of which the most common were skin rash 24%, anaemia and gastrointestinal side effects 17% each. Frequency of opportunistic infections gradually declined after ART. At the end of 1 year of treatment, the cumulative loss to follow up was 7.4%. Conclusions: By following the current national guidelines, the desired immunological and clinical response following initiation of ART can be achieved while minimizing drug toxicity.

Dhaka University Journal of Pharmaceutical Sciences, 2010

The objective of the present study was to evaluate the pattern of adverse drug reactions (ADRs)oc... more The objective of the present study was to evaluate the pattern of adverse drug reactions (ADRs)occurring in cancer patients treated with chemotherapy in tertiary care hospitals in Bangladesh. A prospectivehospital based study over a period of six month was carried out in the Department of oncology, Bangabandhu SheikhMujib Medical University and Dhaka Medical College Hospital. The data were subjected to descriptive analysis. Atotal of 50 patients having ADRs due to cancer chemotherapy were randomly selected. Adverse drug reactions weremostly occurred in the age group between 41-50 years (26%). Considering socio-economic status of cancer patientsmarried persons (82%) have significantly higher risk than unmarried (18%). Prevalence of breast cancer (20%),cervical cancer (14%) and leukemia (16%) were higher and they were treated mostly by adjuvant chemotherapy(46%) and secondly by chemotherapy (38%) alone. In most cases ADRs were developed in patients receivingalkylating agents (40%) and...

Current Cardiology Reports, 2014

There is a clinical need for safety data regarding hydroxychloroquine (HCQ) and chloroquine (CQ) ... more There is a clinical need for safety data regarding hydroxychloroquine (HCQ) and chloroquine (CQ) during the coronavirus (COVID-19) pandemic. We analysed realworld data using the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) database to assess HCQ/CQ-associated cardiovascular adverse events (CVAEs) in pre-COVID-19 reports. Methods: We conducted disproportionality analysis of HCQ/CQ in the FAERS database (07/2014-9/2019), using reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC 025). Results: The full database contained 6 677 225 reports with a mean (±SD) age of 53 (±17) years and 74% females. We identified 4895 reports of HCQ/CQ related adverse events, of which 696 (14.2%) were CVAEs. Compared with the full database, HCQ/CQ use was associated with a higher reporting rate of major CVAEs, including cardiomyopathy (n = 86 [1.8%], ROR = 29.0 [23.3-35.9]), QT prolongation (n = 43 [0.9%], ROR = 4.5 [3.3-6.1]), cardiac arrhythmias (n = 117 [2.4%], ROR = 2.2 [1.8-2.7]) and heart failure (n = 136 [2.8%], ROR = 2.2 [1.9-2.7], all IC₂ > 0). No statistically significant differences were observed between sex and age groups. CVAEs were reported more often in patients with systemic lupus erythematosus and Sjogren's syndrome. HCQ/CQ-associated CVAEs demonstrated subsequent hospitalization and mortality rates of 39% and 8%, respectively. Overdose reports demonstrated an increased frequency of QT prolongation and ventricular arrhythmias (35% and 25%, respectively). Conclusion: In a real-world setting, HCQ/CQ treatment is associated with higher reporting rates of various CVAEs, particularly cardiomyopathy, QT prolongation, cardiac arrhythmias and heart failure. HCQ/CQ-associated CVAEs result in high rates of severe outcomes and should be carefully considered as an off-label indication, especially for patients with cardiac disorders.

National Journal of Physiology, Pharmacy and Pharmacology, 2016

Background: Adverse drug reactions (ADRs) to antiretrovirals have been a matter of concern as the... more Background: Adverse drug reactions (ADRs) to antiretrovirals have been a matter of concern as they can affect patient compliance and treatment outcome. Hence, it is important to detect them early and institute appropriate treatment. Aims and Objective: To assess the prevalence, distribution, causality, severity, predictability and preventability of ADRs to antiretrovirals and to identify risk factors for their development in a tertiary care hospital in South India. Materials and Methods: This was a descriptive observational study. Data were collected from the case records of adult, treatment naïve HIV-positive patients, newly initiated on antiretroviral drugs, January 2012 onward and closure of data set was on 31 st December 2014. Results: A total of 238 cases met the inclusion criteria. Overall, 56 ADRs were noted. ADRs were observed in 39 males and 17 females. They were common in the age group 51-60 years. Anemia was the most common ADR followed by rash and hyperpigmentation. Most of the ADRs observed were of mild severity, requiring neither change in regimen nor any specific treatment. Zidovudine caused the highest number of ADRs, followed by nevirapine and stavudine. Most ADRs occurred within 6 months of starting antiretroviral therapy (ART). Causality relationship between drug and ADR was graded as "possible" according to WHO causality assessment scale. No statistically significant correlation of age, gender, weight, hemoglobin, CD4 count and the presence of opportunistic infections to the development of ADRs were noted. Conclusion: Regular monitoring, an early detection of ADRs to antiretrovirals and their treatment is essential to optimize ART.

Perspectives in Clinical Research, 2015

Journal of the American College of Cardiology, May 1, 2021

Circulation

Healthcare, Dec 2, 2022

Current Atherosclerosis Reports

International Journal of Applied and Basic Medical Research

Circulation

American Journal of Gastroenterology, 2021

Journal of Cellular Biochemistry, 2021

Research Journal of Pharmacy and Technology, 2016

Journal of the American College of Cardiology, 2018

Indian journal of pharmacology

International Journal of Basic and Clinical Pharmacology, 2016

Dhaka University Journal of Pharmaceutical Sciences, 2010

Current Cardiology Reports, 2014

National Journal of Physiology, Pharmacy and Pharmacology, 2016