Clinical Profile of Mucormycosis Patients during Coronavirus Disease 2019 Pandemic: A Retrospective Observational Study.

BACKGROUND: During the coronavirus disease (COVID-19) pandemic, an increased incidence of mucormycosis infection was noted globally, the majority being from India. We aimed to study the clinical profile of the mucormycosis patients during the COVID-19 pandemic admitted at tertiary care centers. MATERIALS AND METHODS: This is a retrospective record-based observation study conducted at Gandhi Medical College, Bhopal. All suspected or laboratory-proven mucormycosis patients were included. Detailed data on demography, clinical features, risk factors, laboratory/radiological findings, and outcomes were recorded. RESULTS: A total of 288 patients were enrolled and 121(42%) showed mucormycosis on potassium hydroxide (KOH) mount. The mean age was 51.52 ± 10.88 years, male:female ratio was 2.3:1. Most common symptom was facial swelling/pain and fever. The most common risk factor was COVID-19 infection (78.5%) followed by the presence of diabetes mellitus (DM) (70.8%) out of which 152 (52.8%) patients were previously diagnosed cases and 52 (18%) patients were newly diagnosed, 159 (55.2%) had a history of corticosteroid use, 87 (30.2%) had a history of use of oxygen support and 67 (23.2%) had hypertension. Most patients had invasion limited to sinus (46.5%) but the presence of DM was associated with an increased risk of cerebral invasion. Out of 288 patients admitted with mucormycosis, 31 patients collapsed to death while the remaining 257 patients were discharged from the hospital. CONCLUSION: It is observed that during the COVID-19 pandemic, hyperglycemia and inappropriate use of corticosteroids were associated with an increased risk of development of mucormycosis in patients with or without DM. We conclude that regular blood glucose monitoring, adequate glycemic control, and judicious evidence-based use of corticosteroids and immunosuppressants in COVID-19 are recommended to reduce the emergence of mucormycosis in such circumstances.

Correlation of Clinical Parameters with Findings of High-resolution Computed Tomography Chest in COVID-19 Patients.

Background: Studies have shown that high-resolution computed tomography (HRCT) of the chest along with clinical parameters is useful in determining the clinical progression, extent of disease and severity of illness in patients with COVID-19. Hence, the present study was done to assess HRCT chest features in patients with COVID-19 infection and to find its association with clinical status in these cases. Materials and methods: This was an observational study over the period of 18 months in patients diagnosed with COVID-19 disease following reverse transcription polymerase chain reaction (RT-PCR). Demographic details, history, clinical parameters, blood and imaging details of enrolled patients were recorded in the study proforma and analyzed using Statistical Package for the Social Sciences (SPSS) software for Windows. Results: The study included 150 COVID-19 patients. HRCT chest severity score was mild in the majority of patients (46.7%), moderate in 24.7%, severe in 5.3%, and negative in 23.3% of cases. HRCT chest severity score was directly correlated with fever, dyspnea, cough, sore throat, reduced appetite, tachypnea, tachycardia, heart rate, respiratory rate, systolic blood pressure, peripheral oxygen saturation, and Glasgow Coma Scale (GCS) score (p < 0.05). Conclusion: The HRCT chest severity score is directly correlated with clinical symptoms, clinical parameters, coexisting comorbidities, and radiological findings in patients with COVID-19 disease. Hence, HRCT chest plays an important role in assessing the severity of COVID-19 disease and predicting the outcome in these patients. How to cite this article: Verma S, Sejwar A, Dube S, et al. Correlation of Clinical Parameters with Findings of High-resolution Computed Tomography Chest in COVID-19 Patients. J Assoc Physicians India 2023;71(11):25-29.

Men Are from Mars, Women Are from Venus: Sex Differences in Insulin Action and Secretion.

Sex difference plays a substantial role in the regulation of glucose metabolism in healthy glucose-tolerant humans. The factors which may contribute to the sex-related differences in glucose metabolism include differences in lifestyle (diet and exercise), sex hormones, and body composition. Several epidemiological and observational studies have noted that impaired glucose tolerance is more common in women than men. Some of these studies have attributed this to differences in body composition, while others have attributed impaired insulin sensitivity as a cause of impaired glucose tolerance in women. We studied postprandial glucose metabolism in 120 men and 90 women after ingestion of a mixed meal. Rates of meal glucose appearance, endogenous glucose production, and glucose disappearance were calculated using a novel triple-tracer isotope dilution method. Insulin action and secretion were calculated using validated physiological models. While rate of meal glucose appearance was higher in women than men, rates of glucose disappearance were higher in elderly women than elderly men while young women had lower rates of glucose disappearance than young men. Hence, sex has an impact on postprandial glucose metabolism, and sex differences in carbohydrate metabolism may have important implications for approaches to prevent and manage diabetes in an individual.

The forgotten role of glucose effectiveness in the regulation of glucose tolerance.

Glucose effectiveness (SG) is the ability of glucose per se to stimulate its own uptake and to suppress its own production under basal/constant insulin concentrations. In an individual, glucose tolerance is a function of insulin secretion, insulin action and SG. Under conditions of declining insulin secretion and action (e.g. type 2 diabetes), the degree of SG assumes increasing significance in determining the level of glucose tolerance both in fasted and postprandial states. Although the importance of SG has been recognized for years, mechanisms that contribute to SG are poorly understood. Research data on modulation of SG and its impact in glucose intolerance is limited. In this review, we will focus on the role of SG in the regulation of glucose tolerance, its evaluation, and potential advantages of therapies that can enhance glucose-induced stimulation of glucose uptake and suppression of its own production in conditions of impaired insulin secretion and action.

Effect of bilateral carotid body resection on the counterregulatory response to hypoglycaemia in humans.

NEW FINDINGS: What is the central question of this study? Hyperoxia blunts hypoglycaemia counterregulation in healthy adults. We hypothesized that this effect is mediated by the carotid bodies and that: (i) hyperoxia would have no effect on hypoglycaemia counterregulation in carotid body-resected patients; and (ii) carotid body-resected patients would exhibit an impaired counterregulatory response to hypoglycaemia. What is the main finding and its importance? Our data indicate that the effect of hyperoxia on hypoglycaemic counterregulation is mediated by the carotid bodies. However, a relatively normal counterregulatory response to hypoglycaemia in carotid body-resected patients highlights: (i) the potential for long-term adaptations after carotid body resection; and (ii) the importance of redundant mechanisms in mediating hypoglycaemia counterregulation. Hyperoxia reduces hypoglycaemia counterregulation in healthy adults. We hypothesized that this effect is mediated by the carotid bodies and that: (i) hyperoxia would have no effect on hypoglycaemia counterregulation in patients with bilateral carotid body resection; and (ii) carotid body-resected patients would exhibit an impaired counterregulatory response to hypoglycaemia. Five patients (three male and two female) with bilateral carotid body resection for glomus tumours underwent two 180 min hyperinsulinaemic, hypoglycaemic (∼ 3.3 mmol l(-1)) clamps separated by a minimum of 1 week and randomized to either normoxia (21% fractional inspired O2 ) or hyperoxia (100% fractional inspired O2). Ten healthy adults (seven male and three female) served as control subjects. Hypoglycaemia counterregulation in carotid body-resected patients was not significantly altered by hyperoxia (area under the curve expressed as a percentage of the normoxic response: glucose infusion rate, 111 ± 10%; cortisol, 94 ± 6%; glucagon, 107 ± 7%; growth hormone, 92 ± 10%; adrenaline, 89 ± 26%; noradrenaline, 79 ± 15%; main effect of condition, P > 0.05). This is in contrast to previously published results from healthy adults. However, the counterregulatory responses to hypoglycaemia during normoxia were not impaired in carotid body-resected patients when compared with control subjects (main effect of group, P > 0.05). Our data provide further corroborative evidence that the effect of hyperoxia on hypoglycaemic counterregulation is mediated by the carotid bodies. However, relatively normal counterregulatory responses to hypoglycaemia in carotid body-resected patients highlight the importance of redundant mechanisms in mediating hypoglycaemia counterregulation.

Effect of hypoxia on heart rate variability and baroreflex sensitivity during hypoglycemia in type 1 diabetes mellitus.

PURPOSE: Patients with type 1 diabetes mellitus exhibit impairments in autonomic and cardiovascular control which are worsened with acute hypoglycemia--thus increasing the risk of adverse cardiovascular events. Hypoxia, as seen with the common comorbidity of sleep apnea, may lead to further autonomic dysfunction and an increased risk of ventricular arrhythmias. Therefore, we hypothesized that heart rate variability (HRV) and baroreflex sensitivity (BRS) would be reduced during hypoglycemia in adults with type 1 diabetes, with a further decline when combined with hypoxia. METHODS: Subjects with type 1 diabetes (n = 13; HbA1c = 7.5 ± 0.3 %, duration of diabetes = 17 ± 5 yrs) completed two 180 min hyperinsulinemic (2 mU/kg TBW/min), hypoglycemic (~3.3 µmol/mL) clamps separated by a minimum of 1 week and randomized to normoxia (SpO2 ~98 %) or hypoxia (SpO2 ~85 %). Heart rate (electrocardiogram) and blood pressure (finger photoplethysmography) were analyzed at baseline and during the hypoglycemic clamp for measures of HRV and spontaneous cardiac BRS (sCBRS). RESULTS: Hypoglycemia resulted in significant reductions in HRV and sCBRS when compared with baseline levels (main effect of hypoglycemia: p < 0.05). HRV and sCBRS were further impaired during hypoxia (main effect of hypoxia: p < 0.05). CONCLUSIONS: Acute hypoxia worsens hypoglycemia-mediated impairments in autonomic and cardiovascular control in patients with type 1 diabetes and may increase the risk of cardiovascular mortality. These results highlight the potential cumulative dangers of hypoglycemia and hypoxia in this vulnerable population.

Hepatic 11ß-hydroxysteroid dehydrogenase type 1 activity in obesity and type 2 diabetes using a novel triple tracer cortisol technique.

AIMS/HYPOTHESIS: Dysregulation of 11ß-hydroxysteroid dehydrogenase (11ß-HSD) enzyme activities are implicated in the pathogenesis of obesity and insulin resistance. The aim of the study was to determine whether hepatic 11ß-HSD type 1 (11ß-HSD-1) enzyme activity differs in people with and without obesity and type 2 diabetes. METHODS: We measured hepatic 11ß-HSD-1 activity in the overnight fasted state in 20 lean non-diabetic participants (LND), 21 overweight/obese non-diabetic participants (OND) and 20 overweight/obese participants with type 2 diabetes (ODM) using a non-invasive approach. One mg doses of [9,12,12-(2)H3]cortisol (D cortisol) and [4-(13)C]cortisone ([(13)C]cortisone) were ingested, while [1,2,6,7-(3)H]cortisol ([(3)H] cortisol) was infused intravenously to enable concurrent measurements of first-pass hepatic extraction of ingested D cortisol and hepatic conversion of ingested [(13)C]cortisone to C13 cortisol derived from the ingested cortisone (a measure of 11ß-HSD-1 activity in the liver) using an isotope dilution technique. One-way ANOVA models and Kruskal-Wallis tests were used to test the hypothesis. RESULTS: Plasma D cortisol and C13 cortisol concentrations were lower in OND than in LND (p < 0.05) over 6 h of the study. There was no difference (p = 0.15) in C13 and D cortisol concentrations between OND and ODM and between LND and ODM for the same study period. Hepatic conversion of [(13)C]cortisone to C13 cortisol was similar between groups. CONCLUSIONS/INTERPRETATION: Hepatic conversion of [(13)C]cortisone to C13 cortisol did not differ between the groups studied. We conclude that hepatic 11ß-HSD-1 activity is similar in individuals who are overweight/obese or who have type 2 diabetes.

Role of the carotid body chemoreceptors in baroreflex control of blood pressure during hypoglycaemia in humans.

Activation of the carotid body chemoreceptors with hypoxia alters baroreceptor-mediated responses. We aimed to examine whether this relationship can be translated to other chemoreceptor stimuli (i.e. hypoglycaemia) by testing the following hypotheses: (i) activation of the carotid body chemoreceptors with hypoglycaemia would reduce spontaneous cardiac baroreflex sensitivity (sCBRS) in healthy humans; and (ii) desensitization of the carotid chemoreceptors with hyperoxia would restore sCBRS to baseline levels during hypoglycaemia. Ten young healthy adults completed two 180 min hyperinsulinaemic [2 mU (kg fat-free mass)(-1) min(-1)], hypoglycaemic (∼ 3.2 µmol ml(-1)) clamps, separated by at least 1 week and randomized to normoxia (arterial partial pressure of O2, 122 ± 10 mmHg) or hyperoxia (arterial partial pressure of O2, 424 ± 123 mmHg; to blunt activation of the carotid body glomus cells). Changes in heart rate, blood pressure, plasma catecholamines, heart rate variability (HRV) and sCBRS were assessed. During hypoglycaemia, HRV and sCBRS were reduced (P < 0.05) and the baroreflex working range was shifted to higher heart rates. When hyperoxia was superimposed on hypoglycaemia, there was a greater reduction in blood pressure and a blunted rise in heart rate when compared with normoxic conditions (P < 0.05); however, there was no detectable effect of hyperoxia on sCBRS or HRV during hypoglycaemia (P > 0.05). In summary, hypoglycaemia-mediated changes in HRV and sCBRS cannot be attributed exclusively to the carotid chemoreceptors; however, the chemoreceptors appear to play a role in resetting the baroreflex working range during hypoglycaemia.

Autonomic control during acute hypoglycemia in type 1 diabetes mellitus.

PURPOSE: We hypothesized that adults with type 1 diabetes mellitus (T1DM) would exhibit impaired heart rate variability (HRV), QT interval, T-wave amplitude, and baroreflex sensitivity (BRS) when compared with healthy controls. In addition, we hypothesized that acute hypoglycemia would result in further adverse changes in measures of autonomic and cardiovascular function. METHODS: A single 180-min hyperinsulinemic (2 mU/kg TBW/min), hypoglycemic (~3.3 umol/mL) clamp was completed in 10 healthy adults and 13 adults with T1DM. Counterregulatory hormones were assessed and measures of heart rate (electrocardiogram) and blood pressure (intra-arterial catheter or finger photoplethysmography) were analyzed at baseline and during the hypoglycemic clamp for measures of HRV, QT interval, T-wave amplitude, and spontaneous cardiac BRS (sCBRS). RESULTS: Baseline measures of HRV, sCBRS, and T-wave amplitude were blunted in adults with T1DM when compared with healthy controls. Hypoglycemia resulted in significant reductions in HRV, sCBRS, and T-wave amplitude and prolonged QT intervals; these changes were not different between adults with T1DM and healthy controls. CONCLUSIONS: Results from the current study show that adults with T1DM exhibit impaired autonomic and cardiovascular function. Additionally, novel findings highlight an effect of acute hypoglycemia to further reduce measures of autonomic and cardiovascular function similarly between adults with T1DM and healthy controls. These results suggest that acute hypoglycemia may worsen impairments in autonomic and cardiovascular control in patients with T1DM, thus increasing the risk of ventricular arrhythmias and cardiovascular mortality.

Baseline findings of a multicentric ambispective cohort study (2021-2022) among hospitalised mucormycosis patients in India.

In India, the incidence of mucormycosis reached high levels during 2021-2022, coinciding with the COVID-19 pandemic. In response to this, we established a multicentric ambispective cohort of patients hospitalised with mucormycosis across India. In this paper, we report their baseline profile, clinical characteristics and outcomes at discharge. Patients hospitalized for mucormycosis during March-July 2021 were included. Mucormycosis was diagnosed based on mycological confirmation on direct microscopy (KOH/Calcofluor white stain), culture, histopathology, or supportive evidence from endoscopy or imaging. After consent, trained data collectors used medical records and telephonic interviews to capture data in a pre-tested structured questionnaire. At baseline, we recruited 686 patients from 26 study hospitals, of whom 72.3% were males, 78% had a prior history of diabetes, 53.2% had a history of corticosteroid treatment, and 80% were associated with COVID-19. Pain, numbness or swelling of the face were the commonest symptoms (73.3%). Liposomal Amphotericin B was the commonest drug formulation used (67.1%), and endoscopic sinus surgery was the most common surgical procedure (73.6%). At discharge, the disease was stable in 43.3%, in regression for 29.9% but 9.6% died during hospitalization. Among survivors, commonly reported disabilities included facial disfigurement (18.4%) and difficulties in chewing/swallowing (17.8%). Though the risk of mortality was only 1 in 10, the disability due to the disease was very high. This cohort study could enhance our understanding of the disease's clinical progression and help frame standard treatment guidelines.

Effects of transaldolase exchange on estimates of gluconeogenesis in type 2 diabetes.

Transaldolase (TA) exchange overestimates gluconeogenesis measured with deuterated water (²H2O). However, it is unknown whether TA differs in people with type 2 diabetes (T2DM). ²H2O was ingested, and [1-¹³C]acetate and [3-³H]glucose were infused in T2DM (n = 10) and healthy nondiabetic (ND; n = 8) subjects. TA was assessed from the ratio of ¹³C3 to ¹³C4 glucose enrichment (¹³C3/¹³C4) measured by ¹³C NMR. Glucose turnover was measured before (~16-h fast) and during hyperglycemic (~10 mM) moderate-dose insulin (~0.35 mU·kg⁻¹·min⁻¹) clamp. ¹³C3/¹³C4 in T2DM vs. ND was <1.0 and not different at baseline and clamp, indicating equivalent TA. To determine whether incomplete triose phosphate isomerase (TPI) exchange contributed to asymmetric ¹³C3/¹³C4, [U-¹³C]glycerol was infused in lieu of [1-¹³C]acetate during a separate visit in a subset of ND (n = 7) subjects. Ratio of ¹³C3/¹³C4 obtained following either tracer was <1.0 at baseline and during clamp, indicating that TPI exchange was essentially complete and did not contribute to asymmetric glucose enrichment. Uncorrected and corrected rates of gluconeogenesis were no different (P = not significant) in T2DM vs. ND both at baseline and during clamp. TA correction resulted in equivalent estimates of corrected gluconeogenesis in T2DM and ND that were ~25-35% lower than uncorrected gluconeogenesis both at baseline and during the clamp. The asymmetric enrichment of glucose from ¹³C-gluconeogenic tracers is attributable to TA exchange and can be utilized to correct for TA exchange. In conclusion, TA exchange does not differ between T2DM and ND under fasting or hyperglycemic clamp conditions, and the ²H2O method continues to provide an accurate estimation of gluconeogenesis.

Assessment of Pulmonary Hypertension in Chronic Kidney Disease Patients using Doppler Echocardiography.

Background: The incidence of chronic kidney disease (CKD) is increasing globally and is associated with significant morbidity and mortality related to the cardiovascular system. There is limited data on pulmonary hypertension (PH) in CKD patients, especially from developing and underdeveloped countries. PH leads to hypoxia which is a significant cause of dyspnea in CKD patients with or without pulmonary edema. Hence, we planned this study to assess the PH in CKD patients using two-dimensional (2D) color Doppler echocardiography. Materials and Methods: This is an observational cross-sectional study. A total of 100 CKD patients on hemodialysis or conservative management were enrolled in the study. Following the collection of demographic data, and routine/specific investigations, these patients were assessed for PH using 2D color Doppler echocardiography. Results: PH was found in 47% of patients with CKD. Left ventricular (LV) hypertrophy, systolic and diastolic dysfunction, dilated right atrium/right ventricular and left atrial/LV chambers, and valvular hypertrophy were other echocardiography findings recorded in these patients. Low hemoglobin levels, high urea/creatinine levels, and duration of hemodialysis in CKD patients were found to be significantly associated with the presence of PH. Conclusion: The majority of CKD patients have PH at various stages of disease-causing unexplained dyspnea in these patients. PH is common in end-stage CKD as compared to patients with a less severe stage of CKD. Hence, CKD patients should be evaluated for PH, especially in the presence of intractable dyspnea.

Hyperglycemia and steroid use increase the risk of rhino-orbito-cerebral mucormycosis regardless of COVID-19 hospitalization: Case-control study, India.

BACKGROUND: In the ongoing COVID-19 pandemic, an increased incidence of ROCM was noted in India among those infected with COVID. We determined risk factors for rhino-orbito-cerebral mucormycosis (ROCM) post Coronavirus disease 2019 (COVID-19) among those never and ever hospitalized for COVID-19 separately through a multicentric, hospital-based, unmatched case-control study across India. METHODS: We defined cases and controls as those with and without post-COVID ROCM, respectively. We compared their socio-demographics, co-morbidities, steroid use, glycaemic status, and practices. We calculated crude and adjusted odds ratio (AOR) with 95% confidence intervals (CI) through logistic regression. The covariates with a p-value for crude OR of less than 0·20 were considered for the regression model. RESULTS: Among hospitalised, we recruited 267 cases and 256 controls and 116 cases and 231 controls among never hospitalised. Risk factors (AOR; 95% CI) for post-COVID ROCM among the hospitalised were age 45-59 years (2·1; 1·4 to 3·1), having diabetes mellitus (4·9; 3·4 to 7·1), elevated plasma glucose (6·4; 2·4 to 17·2), steroid use (3·2; 2 to 5·2) and frequent nasal washing (4·8; 1·4 to 17). Among those never hospitalised, age ≥ 60 years (6·6; 3·3 to 13·3), having diabetes mellitus (6·7; 3·8 to 11·6), elevated plasma glucose (13·7; 2·2 to 84), steroid use (9·8; 5·8 to 16·6), and cloth facemask use (2·6; 1·5 to 4·5) were associated with increased risk of post-COVID ROCM. CONCLUSIONS: Hyperglycemia, irrespective of having diabetes mellitus and steroid use, was associated with an increased risk of ROCM independent of COVID-19 hospitalisation. Rational steroid usage and glucose monitoring may reduce the risk of post-COVID.

Determinants of severity among hospitalised COVID-19 patients: Hospital-based case-control study, India, 2020.

BACKGROUND: Risk factors for the development of severe COVID-19 disease and death have been widely reported across several studies. Knowledge about the determinants of severe disease and mortality in the Indian context can guide early clinical management. METHODS: We conducted a hospital-based case control study across nine sites in India to identify the determinants of severe and critical COVID-19 disease. FINDINGS: We identified age above 60 years, duration before admission >5 days, chronic kidney disease, leucocytosis, prothrombin time > 14 sec, serum ferritin >250 ng/mL, d-dimer >0.5 ng/mL, pro-calcitonin >0.15 µg/L, fibrin degradation products >5 µg/mL, C-reactive protein >5 mg/L, lactate dehydrogenase >150 U/L, interleukin-6 >25 pg/mL, NLR ≥3, and deranged liver function, renal function and serum electrolytes as significant factors associated with severe COVID-19 disease. INTERPRETATION: We have identified a set of parameters that can help in characterising severe COVID-19 cases in India. These parameters are part of routinely available investigations within Indian hospital settings, both public and private. Study findings have the potential to inform clinical management protocols and identify patients at high risk of severe outcomes at an early stage.

Factors associated with mortality among moderate and severe patients with COVID-19 in India: a secondary analysis of a randomised controlled trial.

OBJECTIVE: Large data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce. We analysed the factors associated with mortality in a cohort of moderately and severely ill patients with COVID-19 enrolled in a randomised trial on convalescent plasma. DESIGN: Secondary analysis of data from a Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease. SETTING: 39 public and private hospitals across India during the study period from 22 April to 14 July 2020. PARTICIPANTS: Of the 464 patients recruited, two were lost to follow-up, nine withdrew consent and two patients did not receive the intervention after randomisation. The cohort of 451 participants with known outcome at 28 days was analysed. PRIMARY OUTCOME MEASURE: Factors associated with all-cause mortality at 28 days after enrolment. RESULTS: The mean (SD) age was 51±12.4 years; 76.7% were males. Admission Sequential Organ Failure Assessment score was 2.4±1.1. Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98.9%, 8.4% and 4.0%, respectively. The 28-day mortality was 14.4%. Median time from symptom onset to hospital admission was similar in survivors (4 days; IQR 3-7) and non-survivors (4 days; IQR 3-6). Patients with two or more comorbidities had 2.25 (95% CI 1.18 to 4.29, p=0.014) times risk of death. When compared with survivors, admission interleukin-6 levels were higher (p<0.001) in non-survivors and increased further on day 3. On multivariable Fine and Gray model, severity of illness (subdistribution HR 1.22, 95% CI 1.11 to 1.35, p<0.001), PaO2/FiO2 ratio <100 (3.47, 1.64-7.37, p=0.001), neutrophil lymphocyte ratio >10 (9.97, 3.65-27.13, p<0.001), D-dimer >1.0 mg/L (2.50, 1.14-5.48, p=0.022), ferritin ≥500 ng/mL (2.67, 1.44-4.96, p=0.002) and lactate dehydrogenase ≥450 IU/L (2.96, 1.60-5.45, p=0.001) were significantly associated with death. CONCLUSION: In this cohort of moderately and severely ill patients with COVID-19, severity of illness, underlying comorbidities and elevated levels of inflammatory markers were significantly associated with death. TRIAL REGISTRATION NUMBER: CTRI/2020/04/024775.

Renal replacement therapy in intensive care unit.

Acute renal failure requiring renal replacement therapy (RRT) is a frequent complication in critically ill patients with high morbidity and mortality. Early prediction of who is going to need RRT is clinically useful in the intensive care unit (ICU). Patients' with diuretic resistant pulmonary edema, hyperkalemia/metabolic acidosis refractory to medical therapy and uremic complications (pericarditis, encephalopathy, bleeding) are candidates who need RRT as an earlier intervention with continuous haemofiltration, which might be beneficial to the patient and even prevent clinicians from implementing unnecessary, futile and perhaps injurious escalations in medical therapy (e.g., low-dose dopamine, mannitol boluses, further fluid loading, introduction of additional vasoactive drugs) to rescue kidneys that are beyond rescuing. Recent evidence also suggests that RRT may be useful as an immunomodulator and best initiated early in the course of the patient's illness with multiple system involvement.

Randomized Controlled Trial of a MUFA or Fiber-Rich Diet on Hepatic Fat in Prediabetes.

Context: Increased prevalence of type 2 diabetes mellitus and prediabetes worldwide is attributed in part to an unhealthy diet. Objective: To evaluate whether 12 weeks of high monounsaturated fatty acid (MUFA) or fiber-rich weight-maintenance diet lowers hepatic fat and improves glucose tolerance in people with prediabetes. Design: Subjects underwent a [6, 6-2H2]-labeled 75-g oral glucose tolerance test to estimate hepatic insulin sensitivity and liver fat fraction (LFF) using magnetic resonance spectroscopy before and after intervention. Setting: Mayo Clinic Clinical Research Trials Unit. Participants: 43 subjects with prediabetes. Intervention: Subjects were randomized into three isocaloric weight-maintaining diets containing MUFA (olive oil), extra fiber, and standard US food (control-habitual diet). Outcome Measures: LFF, glucose tolerance, and indices of insulin action and secretion. Results: Body weight was maintained constant in all groups during the intervention. Glucose and hormonal concentrations were similar in all groups before, and unchanged after, 12 weeks of intervention. LFF was significantly lower after intervention in the MUFA group (P < 0.0003) but remained unchanged in the fiber (P = 0.25) and control groups (P = 0.45). After 12 weeks, LFF was significantly lower in the MUFA than in the control group (P = 0.01), but fiber and control groups did not differ (P = 0.41). Indices of insulin action and secretion were not significantly different between the MUFA and control groups after intervention (P ≥ 0.11), but within-group comparison showed higher hepatic (P = 0.01) and total insulin sensitivity (P < 0.04) with MUFA. Conclusions: Twelve weeks of a MUFA diet decreases hepatic fat and improves both hepatic and total insulin sensitivity.

11ß-hydroxysteroid dehydrogenase types 1 and 2 activity in subcutaneous adipose tissue in humans: implications in obesity and diabetes.

CONTEXT: The role of 11ß-hydroxysteroid dehydrogenase types 1 (11ß-HSD-1) and 2 (11ß-HSD-2) enzymes in sc adipose tissue is controversial. OBJECTIVE: The objective of the study was to determine the activity of 11ß-HSD-1 and -2 enzymes in the abdominal and leg sc adipose tissue in obesity and diabetes. DESIGN: 11ß-HSD-1 and -2 enzyme activities in abdominal and leg sc adipose tissue were measured by infusing [2,2,4,6,6,12,12-(2)H7] cortisone (D7 cortisone) and [9,12,12-(2)H3] cortisol (D3 cortisol) via microdialysis catheters placed in sc fat depots. SETTING: The study was conducted at the Mayo Clinic Clinical Research Unit. PARTICIPANTS: Lean nondiabetic (n = 13), overweight/obese nondiabetic (n = 15), and overweight/obese participants with type 2 diabetes mellitus (n = 15) participated in the study. MAIN OUTCOME MEASURES: The conversion of infused D7 cortisone to D7 cortisol (via 11ß-HSD reductase activity) and D3 cortisol to D3 cortisone (via 11ß-HSD dehydrogenase activity) in sc adipose tissue. RESULTS: Enrichment of D7 cortisone and D3 cortisol were similar in the effluents from both sites in all groups. D3 cortisone enrichment did not differ in the three cohorts, indicating that 11ß-HSD-2 enzyme activity (conversion of cortisol to cortisone) occurs equally in all groups. However, D7 cortisol enrichment was detectable in abdominal sc fat of overweight/obese participants with type 2 diabetes mellitus only, implying 11ß-HSD-1 reductase activity (conversion of cortisone to cortisol) occurs in obese subjects with type 2 diabetes. CONCLUSIONS: There is conversion of cortisone to cortisol via the 11ß-HSD-1 enzyme pathway in abdominal sc fat depots in overweight/obese participants with type 2 diabetes mellitus. This observation has significant implications for developing tissue-specific 11ß-HSD-1 inhibitors in type 2 diabetes mellitus.