Mortality comparision in patients receiving either Remdesivir or Remdesivir plus Baricitinib combination in case of moderate to severe COVID-19 Pneumonia: A retrospective study.

Remdesivir and Baricitinib have recently been approved by FDA for the treatment of moderate to severe COVID-19 pneumonia. However, there is limited research work available to assess their beneficial effects. MATERIAL: We conducted retrospective study comparing remdesivir and baricitinib-remdesivir combination therapy in hospitalized adults with moderate to severe Covid-19. All the patients received remdesivir for 5 days and one subgroup had received baricitinib (≤14 days) along with remdesivir. The decision to administer remdesivir only or remdesivir along with baricitinib was the treating clinician's discretion. The primary outcome was to assess the 28-day mortality. OBSERVATION: A total of 50 patients with moderate or severe COVID-19 pneumonia had received either remdesivir alone or both remdesivir and baricinitib during the duration of 1st April 2021 to 30th June 2021in our hospital. The 28-day mortality was 9.091% in the combination group and 14.29% in the remdesivir only group (risk difference= -5.195%, risk ratio for death=0.3634; 95% CI, 0.1281, 3.161; p=0. 0.3086). Patients who had a FiO2 requirement of 100% at any point of time had 100% mortality, irrespective of the drug received. CONCLUSION: Baricitinib and remdesivir combination was superior to remdesivir alone in reducing 28-day mortality among patients with moderate to severe Covid-19, although this difference was statistically insignificant.

A family of amphiphilic dioxidovanadium(V) hydrazone complexes as potent carbonic anhydrase inhibitors along with anti-diabetic and cytotoxic activities.

A family of dioxidovanadium(V) complexes (1-4) of the type [Na(H2O)x]+[VVO2(HL1-4)]- (x = 4, 4.5 and 7) where HL2- represents the dianionic form of 2-hydroxybenzoylhydrazone of 2-hydroxyacetophenone (H2L1, complex 1), 2-hydroxy-5-methylacetophenone (H2L2, complex 2), 2-hydroxy-5-methoxyacetophenone (H2L3, complex 3) and 2-hydroxy-5-chloroacetophenone (H2L4, complex 4), have been synthesized and characterized by analytical and spectral methods. These complexes exhibited the potential abilities to suppress the erythrocytes carbonic anhydrase enzymatic activity in type 1 and type 2 diabetic patients (in vitro), promising antidiabetic activity against T2 diabetic mice (in vivo). They also exhibited significant cytotoxic activity against cervical cancer (SiHa) cells (in vitro) as the IC50 value of complexes 1, 2 and 4 is substantially lower than the value found for cisplatin while that of 3 is comparable and follow the order: 4 < 1 < 2 < 3 and can kill the cells by apoptosis via the generation of reactive oxygen species (ROS). The complexes are soluble both in water and octanol media and also non-toxic at working concentrations. The antidiabetic activity of these four complexes follows the order: 4 > 2 > 1 > 3 while both the carbonic anhydrase and cytotoxic activity follow the order: 4 > 1 > 2 > 3 suggesting that complex 4, containing electron withdrawing Cl atom is the most reactive while 3 with electron donating OCH3 group is the least reactive species. The molecular docking study on hCA-I and hCA-II demonstrates that complexes interact via hydrogen bonding as well as different types of π-stacking.

A Menace without Specific Feature - Scrub Typhus a Reemerging Disease.

INTRODUCTION: Scrub typhus is a re-emerging infectious disease. Though considered as disease of rural areas, this disease has been urbanized and the prevalence has broadened further. Disease has been reported with increasing frequency from various parts of India and has resurgence in north east. It is a disease with multi organ involvement, with or without characteristic eschar and early detection and initial specific treatment is important. MATERIAL: An observational hospital-based study in patients >18years admitted to a tertiary care center in eastern India. Scrub typhus was diagnosed on basis of symptoms with or without eschar and Scrub IgM. Treated with doxycycline (azithromycin in 3 pregnant patients) & clinical course was monitored. An appropriate correlation measure, based on the natures of the variable under study, (e.g.: rank correlation / Pearson correlation/ point biserial correlation) was estimated and subsequently tested at alpha =0.05 level of significance. A p value <0.05 was taken as significant. OBSERVATIONS: A total of 105 patients of scrub typhus were included in present study. It had 66%male and 39% female with the most common age group being 46-60 years. Eschar was found in 33% patients. Neurological manifestation was found in 18% of the patients. Hyponatremia and raised liver enzymes were significantly noticed. 9% patients had Acute respiratory distress syndrome. 4% patients died because of multiorgan dysfunction. Three pregnant patients included in study were treated with azithromycin showed good response and pregnancy outcome was uneventful. CONCLUSIONS: Scrub typhus is no longer a disease of rural India. Physician should have strong suspicion and needs early attempt to diagnose and treat as mostly the disease is featureless and can be treated easily, but delay in starting treatment raises chances of severe complications like encephalitis, ARDS, Macrophage Activation Syndrome. Disease mostly responded with Azithromycin, Doxycycline.

Isotope-specific breath analysis to track the end-stage renal disease during hemodialysis.

The underlying mechanisms towards the progression of end-stage renal disease (ESRD) in chronic kidney disease (CKD) are poorly understood and it still remains a major clinical stumbling block for early detection of CKD. Most patients with CKD pass through ESRD with the necessity of frequent hemodialysis (HD) treatment. At present, plasma urea and creatinine levels are examined in most CKD patients to monitor their health status after dialysis. But it is impossible to get immediate feedback on the patients' health as the conventional tests involve the collection of blood samples, laboratory processing for a prolonged period of time and, finally, analysis of those samples. However, the test results are very important in deciding the treatment plan for those ESRD patients. Here, we show that the enzymatic activity of carbonic anhydrase in erythrocytes is distinctly altered in ESRD subjects under HD. This, in turn, leads to the isotopic enrichments of oxygen-18 (18O) and carbon-13 (13C) of CO2 during respiration in HD treatment. High-resolution cavity-enhanced absorption spectroscopic measurements show that 18O and 13C-isotopic fractionations of breath CO2 are correlated with Kt/V values, suggesting a novel unifying strategy for ESRD patients that can be used as an isotope-specific methodology for non-invasive assessment of dialysis adequacy and hence 12C18O16O and 13C16O16O could be used as novel markers for tracking the physiological parameters of ESRD individuals. Our findings suggest that the monitoring of 18O and 13C isotopes of breath CO2 may facilitate the proper management of advanced CKD patients. The primary advantage of this isotopic breath test is that it may reduce the valuable time lag between the completion of dialysis and obtaining the clinical report on the status of patients' health.

13C isotopic abundances in natural nutrients: a newly formulated test meal for non-invasive diagnosis of type 2 diabetes.

A new method to replace commercially prepared 13C-labelled glucose with naturally available 13C-enriched substrates could result in promotion of the clinical applicability of the isotopic breath test for detection of type 2 diabetes (T2D). Variation of the carbon-13 isotope in human breath depends on the 13C enrichment in the diet taken by subjects. Here, we formulated a new test meal comprising naturally available 13C-enriched foods and subsequently administered it to non-diabetic control (NDC) subjects and those with T2D. We found that the new test meal-derived 13C enrichment of breath CO2 was significantly lower in T2D compared with NDC. Furthermore, from our observations T2D exhibited higher isotopic enrichment of oxygen-18 (18O) in breath CO2 compared with NDC following ingestion of the new meal. We determined the optimal diagnostic cut-off values of 13C (i.e. δ 13C‰ = 7.5‰) and 18O (i.e. Î´ 18O‰ = 3.5‰) isotopes in breath CO2 for precise classification of T2D and NDC. Our new method involving the administration of naturally 13C-abundant nutrients showed a typical diagnostic sensitivity and specificity of about 95%, suggesting a valid and potentially robust global method devoid of any synthetically manufactured commercial 13C-enriched glucose which thus may serve as an alternative diagnostic tool for routine clinical applications.

Targeting erythrocyte carbonic anhydrase and 18O-isotope of breath CO2 for sorting out type 1 and type 2 diabetes.

The inability to envisage the acute onset and progression of type 1 diabetes (T1D) has been a major clinical stumbling block and an important area of biomedical research over the last few decades. Therefore there is a pressing need to develop a new and an effective strategy for early detection of T1D and to precisely distinguish T1D from type 2 diabetes (T2D). Here we describe the precise role of the enzymatic activity of carbonic anhydrase (CA) in erythrocytes in the pathogenesis of T1D and T2D. We show that CA activities are markedly altered during metabolism of T1D and T2D and this facilitates to the oxygen-18 (18O) isotopic fractionations of breath CO2. In our observations, T1D exhibited considerable depletions of 18O-isotopes of CO2, whereas T2D manifested isotopic enrichments of 18O in breath CO2, thus unveiling a missing link of breath18O-isotopic fractionations in T1D and T2D. Our findings suggest that the alterations in erythrocytes CA activities may be the initial step of altered metabolism of T1D and T2D, and breath 18O-isotope regulated by the CA activity is a potential diagnostic biomarker that can selectively and precisely distinguish T1D from T2D and thus may open a potential unifying strategy for treating these diseases.

Insulin sensitivity index (ISI0, 120) potentially linked to carbon isotopes of breath CO2 for pre-diabetes and type 2 diabetes.

New strategies for an accurate and early detection of insulin resistance are important to delay or prevent the acute onset of type 2 diabetes (T2D). Currently, insulin sensitivity index (ISI0,120) is considered to be a viable invasive method of whole-body insulin resistance for use in clinical settings in comparison with other invasive sensitivity indexes like homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI). To investigate how these sensitivity indexes link the (13)C/(12)C-carbon isotopes of exhaled breath CO2 to pre-diabetes (PD) and type 2 diabetes in response to glucose ingestion, we studied excretion dynamics of (13)C/(12)C-isotopic fractionations of breath CO2. Here, we show that (13)C/(12)C-isotope ratios of breath CO2 were well correlated with blood glucose, insulin, glycosylated-hemoglobin as well as with HOMA-IR and 1/QUICKI. Conversely, the strongest correlation was observed between 1/ISI0,120 and breath CO2 isotopes. Consequently, we determined several optimal diagnostic cut-off points of 1/ISI0,120 and (13)CO2/(12)CO2-isotope ratios to distinctively track the evolution of PD prior to the onset of T2D. Our findings suggest that isotopic breath CO2 is a novel method for accurate estimation of ISI0,120 and thus may open new perspectives into the isotope-specific non-invasive evaluation of insulin resistance for large-scale real-time diabetes screening purposes.