Perturbations of immune landscape in COVID-19 associated mucormycosis.

BACKGROUND: A rise in secondary fungal infections during the COVID-19 pandemic necessitates a deeper understanding of the associated immunological perturbations. OBJECTIVES: To evaluate the clinical and immunological characteristics observed in patients with COVID-19 associated mucormycosis (CAM) infection. PATIENTS/ METHODS: Cases of mucormycosis with or post-COVID-19 infection were compared with cases of acute COVID-19 and convalescent COVID-19. Lymphocyte subsets, cytokines and other laboratory markers were compared between the groups. RESULTS: The frequency of proposed risk factors for CAM was diabetes mellitus (77%), recent history of steroid use (69%) and hypoxia during COVID-19 infection (52%). Iron metabolism was dysregulated in CAM patients with low TIBC and total iron. Further, CAM was accompanied with lymphopenia with drastic reduction in B cell counts; however, plasmablasts were not altered. Further, CAM patients had low immunoglobulin levels and antibodies specific to mucor peptide did not increase in CAM suggesting dysfunction in B-cell response. There was increase in activated effector cytotoxic CD8 T cells and NK cells in CAM compared with COVID-19 infection and healthy controls. Among T helper cells, Tregs were reduced and Th-1 frequency was increased in CAM compared with COVID-19 infection. A distinct cytokine signature was evident in CAM with increase in IL-1ß, IFN-γ, IL-6, IL-22, IL-17A, IL-10, IL-2, IL-8, IL-7, IL-21 and GM-CSF. CONCLUSION: This is the first study on immunophenotyping in CAM suggesting the need for long-term monitoring of B-cell function after SARS-CoV-2 in patients with dysregulated glycaemic control and the possible benefit of therapeutic supplementation with intravenous immunoglobulins in CAM.

Factors Associated with Mortality in Coronavirus-Associated Mucormycosis: Results from Mycotic Infections in COVID-19 (MUNCO) Online Registry.

BACKGROUND: COVID-19-associated mucormycosis (CAM) is associated with high morbidity and mortality. MUNCO is an international database used to collect clinical data on cases of CAM in real time. Preliminary data from the Mycotic Infections in COVID-19 (MUNCO) online registry yielded 728 cases from May to September 2021 in four South Asian countries and the United States. A majority of the cases (694; 97.6%) consisted of a mucormycosis infection. The dataset allowed for the analysis of the risk factors for adverse outcomes from CAM and this analysis is presented in this paper. METHODS: The submission of cases was aided by a direct solicitation and social media online. The primary endpoints were full recovery or death measured on day 42 of the diagnosis. All patients had histopathologically confirmed CAM. The groups were compared to determine the contribution of each patient characteristic to the outcome. Multivariable logistic regression models were used to model the probability of death after a CAM diagnosis. RESULTS: The registry captured 694 cases of CAM. Within this, 341 could be analyzed as the study excluded patients with an unknown CAM recovery status due to either an interruption or a lack of follow up. The 341 viable cases consisted of 258 patients who survived after the completion of treatment and 83 patients who died during the period of observation. In a multivariable logistic regression model, the factors associated with an increased risk of mortality include old age (OR = 1.04, 95% CI 1.02-1.07, p = 0.001), history of diabetes mellitus (OR 3.5, 95% CI 1.01-11.9, p = 0.02) and a lower BMI (OR 0.9, 95% CI 0.82-0.98, p = 0.03). Mucor localized to sinus disease was associated with 77% reduced odds of death (OR = 0.23, 95% CI 0.09-0.57, p = 0.001), while cerebral mucor was associated with an increased odds of death (OR = 10.96, 95% CI 4.93-24.36, p = ≤0.0001). CONCLUSION: In patients with CAM, older age, a history of diabetes and a lower body mass index is associated with increased mortality. Disease limited to the sinuses without a cerebral extension is associated with a lower risk of mortality. Interestingly, the use of zinc and azithromycin were not associated with increased mortality in our study.

Analysis of COVID Deaths: A single Centre Experience in Mumbai Medical College.

Objectives To calculate the mortality rate of COVID 19 at our centre. To study age and sex distribution of COVID 19 deaths. To study the duration of hospital stay with mortality. To study the comorbidities associated with mortality. METHODS: This is a retrospective analytical study of COVID 19 deaths which have occurred from April 2020 to January 2021. Death records of patients who were Confirmed positive cases of COVID 19 infection by Antigen positivity or RT PCR (polymerase chain reaction) or CBNAAT were analysed based on the total number of admissions, total deaths, age and gender distribution; duration of hospital stay, co-morbidities. RESULTS: There were 763 deaths in our study. Total admissions were 5762. Mortality rate was 13.2%. Out of these 481 were males and 282 females. The mean age of death was in the group of 60-70 years with a median age of 64.8 years. 221 patients had ≥ 3 comorbidities, 162 had ≥ 2 comorbidities. 172 had single comorbidities and 208 no comorbidities. CONCLUSIONS: COVID 19 affects people of all age groups and gender. It neither spares people with comorbidities nor those without any comorbidities. There is no specific therapy for its treatment. Hence Vaccination, and use of masks, social distancing and sanitization are the policies which will help in the long run.

A Study of Clinical Profile and Outcome of Acute Heart Failure in Elderly Patients.

INTRODUCTION: The significant increase of life expectancies over the last few decades, has lead to a major change in the morbidity and mortality profile of elders. Heart Failure (HF) is predominantly a disorder of the elderly with rates increasing exponentially with time. MATERIAL AND METHODS: The Observational and prospective study was conducted in a tertiary care teaching hospital. The study included all patients >60 years of age diagnosed as acute heart failure as per Boston Criteria. Patients with chronic obstructive pulmonary disease were excluded. Patients were followed till either discharge or death. RESULTS: Total 56 patients were enrolled for the study. Male and female formed 53.57% and 46.43% of study population respectively. Based on Ejection fraction on 2D Echocardiography Diastolic HF (EF >40%) was seen in 30 patients (53.57%) while systolic dysfunction was seen in 26 patients (46.43%). As per Boston score criteria, maximum patient 33 (66.07) fell into range of 8-12 while remaining had score range 5-7. None of the patients were in lesser score range of 1-4. Out of 56 patients 44 (78.57%) were discharged 12 (21.43%) patients expired.

Study of Hepatic Involvement and Thrombocytopenia in Dengue.

OBJECTIVE: The purpose of this study was to assess the pattern of hepatic involvement and thrombocytopenia in patients with dengue fever and time taken for clinical/biochemical recovery. METHODS: This is a retrospective study done in a tertiary centre. A total of 1111 patients with documented dengue fever, either with NS1 antigen/IgM antibody positive report who were admitted between January 2016 to December 2016.The aminotransferase levels and platelet counts were measured on day 1,4 and7. Patients were assessed clinically on day 1,4,7 or till discharge/death accordingly. CONCLUSION: Out of 1111 patients with dengue infection, 993 had either thrombocytopenia or hepatic involvement or both. Majority of patients with thrombocytopenia and hepatic dysfunction recovered between 4-7 days of admission i.e 53.98% and 29.20%. Statistically significant corelation of platelet count and aminotransferase levels with recovery or death of the patient was seen in our study.

Urinary Tract Infection in Elderly: Clinical Profile and Outcome.

OBJECTIVE: Urinary tract infection (UTI) being the most common bacterial infection with considerable morbidity and mortality especially in hospitalized geriatric patients, this study was designed to assess clinical profile, predisposing factors, uropathogen profile causing UTI and to identify associated factors responsible for mortality. METHODS: :Prospective observational study was undertaken among elderly patients aged ≥ 60 years in a tertiary care hospital. 95 indoor patients from medicine wards having symptoms of UTI and urine culture showing significant growth were included in the study. Demographic profile, clinical features, predisposing factors, laboratory features, urine culture reports, antimicrobial susceptibility patterns and outcome were noted and analysed. RESULTS: Of the 95 patients studied, 55.78% were males. 50.52% patients were in age group of 61 to 70 year. Frequency of micturition was the major symptom. Diabetes mellitus was the most common predisposing factor associated with UTI seen in (46.31%) patients. Gram negative organism accounted for 88(92.63%) of bacterial isolates, with Escherichia coli seen in 47.36% of cases. Non-E.coli gram negative organisms such as Pseudomonas, Klebsiella showed lower sensitivity to Levofloxacin, Piperacillin + Tazobactam, Amikacin and Ceftazidime. Mortality rate was 17.89%. Significantly higher mortality was seen in patients with diabetes mellitus (p< 0.0001), complicated UTI (p<0.001), dementia (p<0.0001), serum creatinine >1.4 mg/dl ((p<0.0001) and increasing number of predisposing factors. Fatality was not associated with use of urethral catheters and increased leucocyte count. CONCLUSION: Diabetes mellitus, dementia increases risk of mortality in elderly UTI patients. As gram negative isolates shows drug resistance, prompt diagnosis and the right choice of antimicrobials can play a key role in reducing mortality in elderly UTI patients.

Myasthenia gravis and pure red cell aplasia: a rare association.

This is a case of a patient who presented with generalised weakness, dysphagia and ptosis. Upon evaluating the patient, she was found to have myasthenia gravis (MG) with anaemia and hypothyroidism. Further evaluation for the cause of anaemia revealed that the patient had pure red cell aplasia (PRCA). CT thorax revealed a thymoma. The patient was given packed cell transfusions, steroids and pyridostigmine. The patient improved symptomatically. Her haemoglobin level at follow-up was 9.5 gm/dl. The patient has been posted for thymectomy. This is a rare case of PRCA seen in a patient with MG, with thymoma associated with hypothyroidism.

An unusual cause of hematuria.

Hematuria is a cardinal manifestation of renal disease and forms a cornerstone of nephrologic diagnosis. A systemic approach is required to delineate the source of hematuria to the kidney or urinary tract. We present the case of 14 years old boy who presented to us with history of passing red colour urine since 3 month not associated with pain who was subsequently diagnosed to have of Thin Basement Membrane Disease.

Antiphospholipid syndrome presenting as pulmonary thrombosis and pancreatitis in a young man.

The antiphospholipid syndrome and protein-S deficiency are known prothrombotic conditions. The confirmation of the latter in a patient with a recent antiphospholipid syndrome-associated thrombosis may be difficult as protein-S levels are low in a patient in the wake of recent thrombosis, antiphospholipid antibodies themselves may be targeted against protein-S and oral anticoagulation with warfarin may further bring down protein-S levels. We report a case of a 29-year-old man presenting with widespread unprovoked thrombosis in the form of pulmonary thromboembolism, neck vein thrombosis and pancreatitis. He was found to have antiphospholipid syndrome with low protein-S levels on two occasions. He was anticoagulated with heparin and improved over a 24-day hospital stay marred by the development of an exudative pleural effusion.

Tuberous sclerosis complex presenting as bilateral large renal angiomyolipomas.

Tuberous sclerosis is an inherited disorder that can present with seizures, mental retardation, cutaneous lesions and visceral hamartomas, but can be entirely asymptomatic. The disease occurs in 1:100 000 persons in all races with nearly equal distribution between the sexes. Tuberous sclerosis is often associated with renal angiomyolipomas (AMLs), which occur in up to 80% of these patients. Here we report a case of a patient who presented with bilateral large renal AMLs and was detected to have tuberous sclerosis complex.

Dyskeratosis congenita with portal hypertension of unknown etiology.

Dyskeratosis Congenita (DKC) is a rare progressive bone marrow disorder associated with multi-systemic involvement. It is also characterized by triad of abnormal skin pigmentation, nail dystrophy and mucosal leukoplakia. Liver cirrhosis and portal hypertension are said to be uncommon among these patients. We hereby report a case of an adult male who presented with pancytopenia, abnormal skin pigmentation, nail dystrophy and mucosal leukoplakia. Skin biopsies along with clinical features confirmed the case. Imaging studies were reported as suggestive of and portal hypertension. Liver biopsy done but non-conclusive. Patient's one son and one daughter also had similar skin pigmentation.

A randomized, comparative, multicentric evaluation of atenolol/amlodipine combination with atenolol alone in essential hypertensive patients.

As there is a strong, positive, and continuous correlation between blood pressure and risk of cardiovascular diseases; improved control of blood pressure is necessary to produce maximum reduction in clinical cardiovascular endpoints. The primary objective was to demonstrate that atenolol/amlodipine combination therapy is superior to atenolol monotherapy with respect to mean fall in systolic blood pressure and diastolic blood pressure. The secondary objective was to compare the response rate and to evaluate the tolerability of study medications. This randomized, comparative, multicentric, 12-week study consisted of screening visit followed by baseline visit 48-hours postscreening. All enrolled patients received 7-day placebo washout. Eligible patients were randomized to receive either atenolol 25 mg/amlodipine 2.5 mg or atenolol 25 mg alone. Nonresponders after 4 weeks of therapy were escalated to atenolol 50 mg/amlodipine 5 mg or atenolol 50 mg, respectively. Out of 190 enrolled patients (94: combination group; 96: monotherapy group), 174 patients (84: combination therapy, 90: monotherapy) completed the study. After 4 weeks of therapy, low-dose combination group was superior to low-dose monotherapy with respect to mean fall in SBP (P = 0.008) and DBP (P = 0.021) and response rate (P = 0.012). Also high-dose combination therapy was superior to high-dose monotherapy with respect to mean SBP (P = 0.001), DBP (P = 0.011), and response rate (P = 0.035) at the end of 12 weeks of therapy. At the end of therapy, significantly more number of patients from combination group achieved normalization of BP (SBP < 120 mmHg and DBP < 80 mmHg) (P = 0.009). Thus, once daily treatment with atenolol/amlodipine fixed-dose combination offers superior antihypertensive efficacy over atenolol monotherapy in patients with mild-to-moderate essential hypertension.