Cardiac involvement in coronavirus disease 2019 (COVID-19) commonly accompanies multi-organ system failure with acute respiratory syndrome; however, infrequently myocarditis and pericardial effusions may be isolated, yet fulminant. In this report, we highlight significant variations in cardiac involvement and presentation among patients with COVID-19. This article reports two cases of fulminant myocarditis in COVID-19 positive patients who presented to our facility with contrasting symptoms, laboratory and imaging findings. A 65-year-old patient A had a more typical presentation including respiratory distress, chest pain, ST-segment elevations on electrocardiogram (EKG), lymphopenia, elevated levels of inflammatory markers and cardiac troponin I. A 34-year-old patient B presented with shortness of breath and chest pain similar to patient A; however, she had isolated cardiac involvement with systolic dysfunction and an acute pericardial effusion causing tamponade physiology. Inflammatory marker and cardiac troponin I levels for patient B were within normal range. Patient A had a rapid progression of multi-organ system failure leading to her death within 24 hours from presentation on maximal inopressor support. Patient B, however, is one of few reported cases of cardiac tamponade and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) use in COVID-19 who underwent pericardiocentesis and was additionally managed with colchicine and steroids, leading to complete recovery in systolic function within three weeks from initial presentation. Isolated myocardial dysfunction and pericardial effusions in COVID-19 may have catastrophic sequalae even in the absence of elevated biomarkers described in literature. Therefore, early detection and management of cardiac involvement is warranted. Additionally, the role of mechanical circulatory support devices and VA-ECMO in COVID-19 needs further investigation.
Background:India continues to contribute disproportionately to the global burden of disease and public health research output from India is also known to be not commensurate with her healthcare needs. We carried out the present study to assess if clinical trials were in line with the health care needs of the country by auditing the clinical trials registry of India.Materials and Methods:All the clinical studies registered in CTRI between July 20, 2007 and December 31, 2015 were searched in the “Trial Search” section. The total number of studies, their phases of development, and therapeutic areas were assessed. Trials in each therapeutic area was compared with the disease burden (DALYs) in that area taken from Global Health Estimates [2014] Summary Tables of the WHO. The number of trials conducted per state in India was also compared with the population of that state [Census 2011].Results:A total of 6474 studies were registered of which 3325 (51.4%) were clinical trials. The state of Maharashtra had the highest number trials [16.4%] followed by Karnataka (11.6%) and Tamil Nadu (10%). Populous states like Uttar Pradesh (5.3%) and Bihar (1.4%) had far fewer trials. The largest number of trials was in the area of cancer (16.4%), followed by diabetes (12.1%) and cardiovascular diseases (10.1%). Infectious and parasitic diseases had the highest DALYs (82,681) and ranked first in disease burden but accounted for only 5% of the total trials and ranked 7th according to number of trials. Cancer ranked first in the number of trials (16.4%), but ranked 6th based on DALYs.Conclusion:Clinical trials conducted in India are not in consonance with her health care needs. Strengthening the capacity for conducting trials in the populous states and the north-eastern part of the country is necessary to allow a more equitable selection of participants. The government should introduce policies to encourage new drug development in areas where needed the most.
Introduction It is increasingly recognized that transformed (T) diffuse large B cell lymphoma (DLBCL) is a clinically and biologically distinct entity from de novo DLBCL. Dose escalated etoposide, doxorubicin, vincristine, cyclophosphamide and prednisone with rituximab (DA-EPOCH-R) is effective in aggressive large B cell lymphomas including de novo DLBCL, Burkitt lymphoma, high grade B cell lymphoma with BCL2-Myc rearrangement and primary mediastinal B cell lymphoma. However, outcomes of transformed DLBCL (T-DLBCL) treated with DA-EPOCH-R are not well-studied. Here, we describe our experience with T-DLBCL after treatment with DA-EPOCH-R. Methods All adult patients with DLBCL diagnosed and treated with DA-EPOCH-R at Medstar Washington Hospital Center from January 2000 to November 2018 were included in this retrospective study. Data was collected from review of electronic medical records. All transformations were biopsy-proven. T-DLBCL was defined as either biopsy-confirmed DLBCL with background of indolent lymphoma (concurrently transformed (CT) DLBCL) or sequential development of DLBCL in a case of known indolent lymphoma (sequentially transformed, (ST) DLBCL). Patient characteristics including age, sex, race were recorded. Stage, extranodal disease, international prognostic index (IPI) of DLBCL were recorded. For patients with CT and ST DLBCL, histology and prior treatment of indolent lymphoma were recorded. Study objectives were to assess response rates, progression free survival (PFS) and overall survival (OS) for de novo DLBCL, CT-DLBCL and ST-DLBCL treated with DA-EPOCH-R. Fisher's exact test was used to compare categorical variables between the groups. Kaplan-Meier method was used to calculate survival curves. Log rank test was used to compare survival between de novo DLBCL, CT-DLBCL and ST-DLBCL. Results Of 183 DLBCL patients treated during the study period, 34 had T-DLBCL (17 CT-DLBCL and 17 ST-DLBCL). Total 91 received DA-EPOCH-R (25 transformed, 66 de novo) and were included in our study. Median age was 56 (23-84). Sixty percent patients were males and 42% were white. Out of 25 Tx DLBCL, 11 had CT-DLBCL and 14 had ST-DLBCL. Patients with T-DLBCL (CT and ST) had higher odds of being white, having advanced stage, extra-nodal disease and high IPI. [OR: 2.6 (CI951.7-6), 4.1 (CI951.6-10), 2.8 (CI95 2.8 (1.8-7) and 2.7 (CI951.2-6), respectively. P <0.001]. Cell of origin, BCL2 and BCL6 expression was not available for all DLBCL patients. Follicular lymphoma was the most common underlying indolent lymphoma (13), followed by chronic lymphocytic leukemia (5), marginal zone lymphoma (3), low grade non-Hodgkin lymphoma not otherwise specified (3) and lymphoplasmacytic lymphoma (1). Seven of T-DLBCL had received prior rituximab and 2 had received prior anthracycline. For ST-DLBCL patients, median time to transformation was 2.25 years (0.3-15). There was no significant difference in ORR (85%, 86%, 91%) and CR (82%, 84%, 89%) of DA-EPOCH-R treated CT, ST and de novo DLBCL, respectively. Median follow up was 5 years. Median PFS and OS for CT and de novo DLBCL were not reached. ST DLBCL had median PFS and OS of 21 years and 37 years, respectively. There was no significant difference between 2-year PFS and OS of CT, ST and de novo DLBCL treated with DA-R-EPOCH. (Table 1). Conclusion T-DLBCL is more likely to have aggressive features such as advance stage, extra nodal disease and high IPI. Despite this, DA-EPOCH-R treated T-DLBCL has outcomes comparable to de novo DLBCL. Large, prospective studies are needed to examine efficacy of DA-EPOCH-R in T-DLBCL. Figure. Disclosures No relevant conflicts of interest to declare.
Tuberculosis (TB) has been a devastating human illness for thousands of years. According to the WHO, around 10.4 million new cases of tuberculosis are identified every year, with 1.8 million deaths. To reduce these statistics and the mortality rate, an early and accurate TB diagnosis is essential. This study offers a highly sensitive and selective electrochemical biosensor for Mycobacterium tuberculosis (MTB) detection based on a ternary nanocomposite of reduced graphene oxide, polydopamine, and gold nanoparticles (rGO-PDA-AuNP). Avidin-biotin coupling was used to bind the MTB probe DNA onto the rGO-PDA-AuNP modified glassy carbon electrode (ssDNA/avidin/rGO-PDA-AuNP). UV-Visible, Raman, XRD, and TEM were used to evaluate the structural and morphological characteristics of rGO-PDA-AuNP. Furthermore, DNA immobilization is validated using FESEM and FT-IR techniques. The modified electrodes were electrochemically analyzed using cyclic voltammetry (CV) and linear sweep voltammetry (LSV), and the results indicate that the produced electrode can detect target DNA up to 0.1 × 10−7 mM with 2.12 × 10−3 mA µM−1 sensitivity and a response time of 5 s. The constructed genosensor displayed high sensitivity and stability, and it also provides a unique strategy for diagnosing MTB at an early stage. Furthermore, our rGO-PDA-AuNP/GCE-based electrochemical platform has broad potential for creating biosensor systems for detecting various infectious pathogens and therapeutically significant biomarkers.
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