Thrombolysis in STEMI in the era of COVID - Holding fort in cardiologist deficit locales.

During the COVID-19 pandemic, the pharmaco-invasive approach in the management of ST Elevation Myocardial Infarction (STEMI) played a vital role in saving many lives. A retrospective observational study was conducted wherein 134 patients presenting with STEMI between (Dec 2019-Mar 2022) were thrombolysed with either streptokinase or tenecteplase in a centre where primary PCI was not available. There was no significant difference in the outcomes and their predictors between the SK and TNK groups. A prospective study with a larger sample size in the Indian population will be able to provide more substantial and promising results for further interventions.

Knowledge and practice of radiation safety in the Catherization laboratory among Interventional Cardiologists - An online survey.

An Online Survey among Interventional Cardiologists (IC) assessed the knowledge (five questions) and practice of radiation safety (eleven questions). Out of 185 respondents, knowledge of annual radiation dose (2% knew), LAO cranial view giving maximum radiation (48%) and benefit of assessment of radiation exposure with dose area product (31%) was limited. Radiation safety was practiced "whenever I remember" in 37-59%. Radiation safety practices were optimal frame rate selection (32%), distancing from x-ray unit (17%), collimation use (30%), positioning the image detector close to chest (91%) and personal dosimeters use (40%). A major gap exists between knowledge and practice of radiation safety.

An Evaluation of Efficacy and Safety of Tofacitinib, A JAK Inhibitor in the Management of Hospitalized Patients with Mild to Moderate COVID-19 - An Open-Label Randomized Controlled Study.

Several systemic anti-inflammatory and immunomodulatory agents were tried in the management of hyper inflammatory manifestations of COVID 19. JAK inhibitors have been widely deployed in rheumatology due to their benefits in managing uncontrolled inflammation. Tofacitinib is one of the most widely studied immunomodulators in rheumatology. We assessed the safety and efficacy of Tofacitinib in an open-labeled randomized control study, in addition to the standard of care (SOC) in hospitalized adults with mild to moderate COVID-19 pneumonia. Patients (n=100) with COVID 19 pneumonia admitted during October -December 2020 were randomly assigned to either control (N=50) (SOC treatment alone) or to study groups (N=50) receiving Tofacitinib in addition. Patients, reporting positive RT-PCR for SARS-COV2 and radiological evidence of pneumonia were hospitalized for over 7 days. The study group received Tofacitinib for 14 days irrespective of the discharge status and was followed up to 28 days. There was a greater relative reduction in levels of important markers of inflammation in the Tofacitinib group than in the control group (CRP:78% vs 45%; Ferritin:15% vs 10%; D. Dimer: 37% vs 15%) although there were no differences in duration of hospitalizations or oxygen requirement. Tofacitinib, 10 mg was well-tolerated and was devoid of any serious adverse event. We are the first to record the benefits of Tofacitinib in India to our knowledge although a Brazilian study conducted around the same time showed mortality benefit in severe COVID. We conclude that Tofacitinib use is safe and aids in the reduction of the overwhelming inflammatory response during COVID-19 infections.

Efficacy and Safety of Tracnil™ Administration in Patients with Dermatological Manifestations of PCOS: An Open-Label Single-Arm Study.

Myo-inositol's role in improving acne by reducing hyperandrogenism has been demonstrated in PCOS patients. Inositol and associated molecules display inhibitory properties against 5-α reductase, COX-2, and lipase enzymes in addition to their antimicrobial and anti-inflammatory properties. However, the role of myo-inositol is not well established in women patients with normal hormone levels but with clinical manifestations of PCOS. In this study, we evaluate the efficacy of Tracnil™, a combination of myo-inositol with folic acid and vitamin D3, in resolving acne in overweight women of menstruation age displaying normal hormone levels. It is a single-arm study conducted at 2 centers including 33 women with acne, hirsutism, and menstrual irregularities. Acne and hirsutism were assessed by manual lesion count, modified Cook's scale, and modified Ferriman-Gallwey hirsutism score (mFGHS). Hormone levels and safety parameters were assessed throughout the study. Our results show that Tracnil™ monotherapy could drastically reduce acne-related lesions of both inflammatory and noninflammatory types as quickly as 8 weeks. Additionally, it improves hirsutism and menstrual irregularities. Adverse reactions were negligible during the whole study period with no drastic side effects reflected by a modulatory effect on hormone levels. Despite the subjects having normal hormone levels, the acne treatment with myo-inositol and vitamin D3 shows improvement in hirsutism and regularization of menstrual cycle. Therefore, we attribute the mechanism of action of Tracnil™ to modulation of receptor sensitivity to sex hormones or other downstream processing events. Tracnil™ may be considered as a first-line treatment for dermatological manifestations of PCOS even in the absence of significant hormonal abnormalities. This treatment is practically implementable in a dermatologists's office practise.

Pulmonary infection with an interferon-gamma-producing Cryptococcus neoformans strain results in classical macrophage activation and protection.

Alternative macrophage activation is associated with exacerbated disease in murine models of pulmonary cryptococcosis. The present study evaluated the efficacy of interferon-gamma transgene expression by Cryptococcus neoformans strain H99gamma in abrogating alternative macrophage activation in infected mice. Macrophage recruitment into the lungs of mice after infection with C. neoformans strain H99gamma was comparable with that observed in mice challenged with wild-type C. neoformans. However, pulmonary infection in mice with C. neoformans strain H99gamma was associated with reduced pulmonary fungal burden, increased pulmonary Th1-type and interleukin-17 cytokine production, and classical macrophage activation as evidenced by increased inducible nitric oxide synthase expression, histological evidence of enhanced macrophage fungicidal activity, and resolution of inflammation. In contrast, progressive pulmonary infection, enhanced Th2-type cytokine production, and the induction of alternatively activated macrophages expressing arginase-1, found in inflammatory zone 1, Ym1, and macrophage mannose receptor were observed in the lungs of mice infected with wild-type C. neoformans. These alternatively activated macrophages were also shown to harbor highly encapsulated, replicating cryptococci. Our results demonstrate that pulmonary infection with C. neoformans strain H99gamma results in the induction of classically activated macrophages and promotes fungal clearance. These studies indicate that phenotype, as opposed to quantity, of infiltrating macrophages correlates with protection against pulmonary C. neoformans infection.

Insights into the mechanisms of protective immunity against Cryptococcus neoformans infection using a mouse model of pulmonary cryptococcosis.

Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening pneumonia and meningoencephalitis in immune compromised individuals. Previous studies have shown that immunization of BALB/c mice with an IFN-gamma-producing C. neoformans strain, H99gamma, results in complete protection against a second pulmonary challenge with an otherwise lethal cryptococcal strain. The current study evaluated local anamnestic cell-mediated immune responses against pulmonary cryptococcosis in mice immunized with C. neoformans strain H99gamma compared to mice immunized with heat-killed C. neoformans (HKC.n.). Mice immunized with C. neoformans strain H99gamma had significantly reduced pulmonary fungal burden post-secondary challenge compared to mice immunized with HKC.n. Protection against pulmonary cryptococcosis was associated with increased pulmonary granulomatous formation and leukocyte infiltration followed by a rapid resolution of pulmonary inflammation, which protected the lungs from severe allergic bronchopulmonary mycosis (ABPM)-pathology that developed in the lungs of mice immunized with HKC.n. Pulmonary challenge of interleukin (IL)-4 receptor, IL-12p40, IL-12p35, IFN-gamma, T cell and B cell deficient mice with C. neoformans strain H99gamma demonstrated a requirement for Th1-type T cell-mediated immunity, but not B cell-mediated immunity, for the induction of H99gamma-mediated protective immune responses against pulmonary C. neoformans infection. CD4(+) T cells, CD11c(+) cells, and Gr-1(+) cells were increased in both proportion and absolute number in protected mice. In addition, significantly increased production of Th1-type/pro-inflammatory cytokines and chemokines, and conversely, reduced Th2-type cytokine production was observed in the lungs of protected mice. Interestingly, protection was not associated with increased production of cytokines IFN-gamma or TNF-alpha in lungs of protected mice. In conclusion, immunization with C. neoformans strain H99gamma results in the development of protective anti-cryptococcal immune responses that may be measured and subsequently used in the development of immune-based therapies to combat pulmonary cryptococcosis.

Biofilm formation by Cryptococcus neoformans under distinct environmental conditions.

Cryptococcus neoformans is an opportunistic fungal pathogen with a propensity to infect the central nervous system of immune compromised individuals causing life-threatening meningoencephalitis. Cryptococcal biofilms have been described as a protective niche against microbial predators in nature and shown to enhance resistance against antifungal agents and specific mediators of host immune responses. Based on the potential importance of cryptococcal biofilms to its survival in the human host and in nature, these studies were designed to investigate those factors that mediate biofilm formation by C. neoformans. We observed that C. neoformans preferentially grew as planktonic cells when cultured under specific conditions designed to mimic growth within host tissues (37 degrees C, neutral pH, and ~5% CO(2)) or phagocytes (37 degrees C, acidic pH, and ~5% CO(2)) and as biofilms when cultured under conditions such as those encountered in the external environment (25-37 degrees C, neutral pH, and ambient CO(2)). Altogether, our studies suggest that conditions similar to those observed in its natural habitat may be conducive to biofilm formation by C. neoformans.