Serum iron indices in COVID-19-associated mucormycosis: A case-control study.

BACKGROUND: Whether dysregulated iron metabolism is associated with COVID-19-associated mucormycosis (CAM) remains unknown. Herein, we compare the serum iron indices in COVID-19 subjects with and without mucormycosis. METHODS: We conducted a case-control study enrolling COVID-19 participants with and without mucormycosis. We compared the baseline serum iron indices (iron, ferritin, total iron-binding capacity [TIBC], unsaturated iron-binding capacity and percentage transferrin saturation) between CAM cases and COVID-19 controls. Additionally, we performed a multivariate logistic regression analysis to assess whether any iron indices are associated with CAM. RESULTS: We enrolled 28 CAM cases (mean age 53.6 years old; 78.6% men) and 26 controls (mean age 57.2 years old; 73.1% men). Rhino-orbital (±cerebral) mucormycosis (85.7%) was the most clinical presentation. Diabetes mellitus was more frequent in the cases than controls (75% vs. 42.3%; p = .015). Hypoxaemia during COVID-19 illness was more common in controls than cases. The mean serum iron values (33 vs. 45 µg/dl, p = .03) and TIBC (166.6 vs. 201.6 µg/dl, p = .003) were significantly lower in CAM cases than controls. On multivariate analysis, we found a lower TIBC (odds ratio [OR] 0.97; 95% confidence interval [CI], 0.95-0.99) and diabetes mellitus (OR 5.23; 95% CI, 1.21-22.68) to be independently associated with CAM after adjusting for serum iron, ferritin and glucocorticoid therapy. The case fatality rate of CAM was 73.9%. The iron indices were not significantly different between CAM survivors and non-survivors. CONCLUSIONS: The CAM is associated with lower TIBC levels than COVID-19 subjects without mucormycosis, suggesting dysregulated iron metabolism in its pathogenesis. Further studies are required to confirm our preliminary observations.

Is there an association between zinc and COVID-19-associated mucormycosis? Results of an experimental and clinical study.

BACKGROUND: The enormous increase in COVID-19-associated mucormycosis (CAM) in India lacks an explanation. Zinc supplementation during COVID-19 management is speculated as a contributor to mucormycosis. We conducted an experimental and clinical study to explore the association of zinc and mucormycosis. METHODS: We inoculated pure isolates of Rhizopus arrhizus obtained from subjects with CAM on dichloran rose Bengal chloramphenicol (DRBC) agar enriched with (three different concentrations) and without zinc. At 24 h, we counted the viable colonies and measured the dry weight of colonies at 24, 48 and 72 h. We also compared the clinical features and serum zinc levels in 29 CAM cases and 28 COVID-19 subjects without mucormycosis (controls). RESULTS: We tested eight isolates of R arrhizus and noted a visible increase in growth in zinc-enriched media. A viable count percentage showed a significantly increased growth in four of the eight isolates in zinc-augmented DRBC agar. A time- and concentration-dependent increase in the mean fungal biomass with zinc was observed in all three isolates tested. We enrolled 29 cases of CAM and 28 controls. The mean serum zinc concentration was below the reference range in all the subjects and was not significantly different between the cases and controls. CONCLUSIONS: Half of the R arrhizus isolates grew better with zinc enrichment in vitro. However, our study does not conclusively support the hypothesis that zinc supplementation contributed to the pathogenesis of mucormycosis. More data, both in vitro and in vivo, may resolve the role of zinc in the pathogenesis of CAM.

Circulating cardiac biomarkers and echocardiographic abnormalities in patients with scrub typhus: A prospective cohort study from a tertiary care center in North India.

BACKGROUND & OBJECTIVES: Cardiac injury in scrub typhus is uncommonly reported. We studied the incidence and clinical significance of cardiac involvement among seventy consecutive adult patients of scrub typhus, using circulating cardiac biomarkers, including N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), troponin T, creatine kinase-muscle/brain isoenzyme (CK-MB) and 2D-echocardiography. METHODS: This was a hospital-based prospective cohort study conducted in the medical emergency of PGIMER, Chandigarh, India. Seventy consecutive patients aged 12 years and above with the diagnosis of scrub typhus were enrolled. RESULTS: Elevations of NT pro-BNP, troponin T, and CK-MB levels were observed in 70 (100%), 51 (72.8%), and 29 (41.4%) patients, respectively. Echocardiography detected reduced ejection fraction (EF) in 30 patients (42.8%) with mild reduction (EF 45-54 %) in 20 (28.5%) and moderate reduction (EF 30-44%) in 10 (14.3%). The age showed a significant difference with EF (p-value 0.003), and the patients with moderate reduction were younger (mean age of 20.7 ± 5.6 years). Pericardial effusion was found in nine patients (12.9%). Increased circulating levels of all the three cardiac biomarkers showed statistically significant association with a systolic dysfunction on echocardiography, and elevated CK-MB level further predicted a longer duration of hospital stay (p-value 0.002). No statistically significant association was observed between cardiac biomarkers or reduced EF and mortality. INTERPRETATION & CONCLUSION: Cardiac injury is a common condition among patients with scrub typhus admitted in a medical emergency; however, it does not influence in-hospital mortality.

Fever of Unknown Origin in Older Adults: A Prospective Observational Study from North India.

OBJECTIVES: Fever of unknown origin (FUO) has different etiology in different age groups. We aimed to determine the spectrum of FUO in older patients and to establish the underlying etiology. METHODS: This was a hospital-based prospective observational study conducted between January 2018 to June 2019 at Postgraduate Institute of Medical Education and Research, Chandigarh, India. Fifty-one consecutive patients aged 60 years and above met the qualitative criteria of FUO. RESULTS: The etiological distribution was infections in 21 patients (41.2%), malignancies in 16 (31.4%) and noninfectious inflammatory disorders in 8 (15.7%). Six patients (11.8%) remained undiagnosed. Among infections, 15 patients (29.4%) had tuberculosis, and 10 had an extrapulmonary disease. Twelve out of 16 cases with malignancies had a hematological cause, and eight had lymphoma. ;Regarding decisive methods of diagnosis, 18F-fluorodeoxyglucose positron emission tomography was diagnostic in 17 out of 27 patients (63%) and computed tomography in 21 out of 42 cases (50%). Imaging or endoscopy-guided procedures provided a diagnostic clue in 12 out of 14 patients (85.7%), and bone marrow examination results were useful in 9 out of 19 (47.4%). CONCLUSIONS: Infections and malignancies contributed to about three-fourths of cases, with tuberculosis and lymphoma being the commonest etiologies.

Scrub typhus cholecystitis.

Acute acalculous cholecystitis is usually seen in association with systemic medical illness, or after surgery, trauma or burn and is considered as a more severe disease than acute calculous cholecystitis. We recently had the opportunity of observing a patient who was admitted in a surgical emergency with clinical features of acute cholecystitis and was found to have Orientia tsutsugamushi infection after a strong clinical suspicion of acute tropical fever illness.

Dengue: Uncommon Neurological Presentations of a Common Tropical Illness.

Dengue is a common arthropod-borne flavivirus and commonly manifests as fever, bleeding diathesis, and capillary leak syndrome. Neurological manifestations are uncommon except for encephalopathy. We have recently had the opportunity of observing two patients with rare neurological complications of dengue, transverse myelitis, and Guillain-Barré syndrome. Both the cases had good neurological recovery with steroid and intravenous immunoglobulin, respectively. How to cite this article: Singh H, Pannu AK, Bhalla A, Suri V, Kumari S. Dengue: Uncommon Neurological Presentations of a Common Tropical Illness. Indian J Crit Care Med 2019;23(6):274-275.

Not all febrile critical illness with rash is infective: Drug reaction may be a mimic.

We report a case of ciprofloxacin-related drug rash with eosinophilia and systemic symptoms (DRESS) which was initially diagnosed and managed on the line of tropical fever. Later, a diagnosis of definite case of DRESS was made according to the RegiSCAR scoring system and the patient was managed with the removal of ciprofloxacin along with steroids. DRESS is a great masquerader. The diagnosis should be highly suspected in the presence of fever, skin rash, liver involvement, and hypereosinophilia.

Safety and Efficacy of a Single Dose of Anti-D (WinRho®) in Severe Thrombocytopenia Secondary to Dengue Virus Infection.

OBJECTIVE: To evaluate the efficacy of a single intravenous (IV) dose of anti-D in severe thrombocytopenia (<20,000) due to dengue virus (DEV) infection. MATERIALS AND METHODS: An open label, investigator-initiated, randomized interventional study was conducted that included thirty dengue patients (all positive for IgM enzyme-linked immunosorbent assay) with severe thrombocytopenia (<20,000/mm3). Patients were randomized to receive anti-D (50 µg/kg single IV dose) plus supportive therapy or supportive therapy alone. RESULTS: The rate of rise in platelet count was significantly high in the intervention group at 24, 36, and 48 h. At the end of 48 h, 60% patients in the intervention group achieved a platelet count of ≥50,000/mm3 as compared to 6.7% in the control group (P = 0.0019). The requirement of the platelet concentrate infusion in the control group was significantly higher, i.e. 342 ml (±193) as compared to the intervention group requiring only 187 ml (±79). The intervention group showed a significant improvement in bleeding manifestations in all the patients by 24 h in Grade 2 bleed (P = 0.032) and by 48 h in Grade 1 bleed (P = 0.014). CONCLUSIONS: Severe thrombocytopenia (≤20,000/mm3) secondary to DEV infection was rapidly and safely reversed by administration of a single dose of 50 µg/kg (250 IU/kg) anti-D IV.

Changing spectrum of primary pyomyositis in North India.

Recent data have demonstrated the changing epidemiology of primary pyomyositis worldwide. Our hospital-based retrospective study investigated the clinical and microbiological spectrum of primary pyomyositis between 2013 and 2021 in PGIMER (Chandigarh), India. Over a quarter had predisposing conditions, mainly diabetes mellitus and immunosuppressive therapy. Fever, muscle pain, local swelling and breathlessness were the usual presentations, with quadriceps, iliopsoas and gluteal muscles commonly affected. Staphylococcus aureus was the predominant cause, with c.50% methicillin-resistant strains. Almost two-thirds presented with metastatic infection (stage 3 pyomyositis), frequently with septic lung emboli. Patients with methicillin-sensitive and resistant Staphylococcus aureus had a similar incidence of metastatic infection. In-hospital mortality was c.10% and was strongly associated with a high international normalised ratio. Primary pyomyositis remains a significant problem, with a dramatic increase in community-associated methicillin-resistant Staphylococcus aureus.

Efficacy of a low dose of antivenom for severe neuroparalysis in Bungarus caeruleus (common krait) envenomation: a pilot study.

Introduction: Despite the widespread use of antivenom for the treatment of snakebite envenoming in the Indian subcontinent, the ideal dose of antivenom has been a point of contention. Low-dose regimens can economize on a scarce resource in low- and middle-income countries. This study assessed the effectiveness of a low-dose (10 vials) antivenom regimen compared to the usual 20 vials in patients with krait bite neuroparalysis requiring mechanical ventilation. Methods: This study was a prospective controlled pilot study conducted in a tertiary-care hospital in north India. Participants were eligible if they were ≥12 years old, had krait bite neurotoxicity, showed severe paralysis requiring mechanical ventilation, and had access to antivenom therapy within 24 h of the bite. The primary outcome was the duration of mechanical ventilation, and the secondary outcomes were the length of hospital stay and in-hospital survival. Results: Fifteen patients received 10 vials of antivenom, and 25 received 20 vials. The two treatment groups had similar baseline demographics, clinical and laboratory features, snakebite severity scores, and median time from snakebite to initiation of antivenom therapy. The low-dose regimen was as effective as the standard dose concerning the median duration of mechanical ventilation (41 h vs. 55 h, P = 0.094), the median length of stay (78 h vs. 85.5 h, P = 0.360), and in-hospital deaths (1 vs. 3, P = 1.000). The incidence of ventilator-associated pneumonia was similar between the two groups (1 vs 3, P = 1.000). Conclusion: A low dose of antivenom effectively treats patients with severe krait bite neuroparalysis.

Occult paraquat poisoning causing pneumomediastinum and organizing pneumonia.

Pneumomediastinum is not an uncommon manifestation of lung toxicity in acute paraquat ingestion. The condition is almost invariably seen with other lung parenchymal abnormalities such as consolidations, ground-glass opacities and interlobular septal thickening. The diagnosis may be challenging in cases with no history of toxin exposure, presentation with a subacute illness and/or absence of typical local or systemic features of paraquat toxicity.

The Utility of Quantitative D-Dimer Assay as a Biomarker in the Diagnosis and Exclusion of Cerebral Venous Sinus Thrombosis.

The utility and sensitivity of quantitative D-Dimer assay to rule out the diagnosis of deep vein thrombosis is well established. We extrapolated this principle to evaluate the utility of D-Dimer assay in exclusion of cerebral venous sinus thrombosis (CVST). As advanced imaging modalities required for the diagnosis of CVST might not be available everywhere, it is important to have a sensitive biomarker and a clinical decision rule which can assist in the diagnosis. Patients undergoing CT/MR Venography of the brain with the suspicion of CVST were enrolled. Quantitative D-Dimer assay was performed in those who had CVST on CT/MR Venography and was compared with those who did not. A Clinical decision rule for the diagnosis of CVST was formulated using logistic regression analysis. Receiver operating characteristic analysis evaluating the diagnostic accuracy of D Dimer for patients with CVST as compared to those who did not revealed an AUROC of 0.694. D-Dimer levels of < 300 ng/mL had a sensitivity of 90% for the exclusion of CVST. After logistic regression analysis, a clinical decision rule with a total score of 16 and individual components of Female gender (2 points), Headache (7 points), D-Dimer levels of ≥ 792 ng/mL (7 points) was proposed. D-Dimer had a poor diagnostic accuracy for differentiation of patients who had CVST from those who did not, however, had a high sensitivity at values < 300 ng/mL. The proposed clinical decision rule with a score of ≥ 9 had a good diagnostic accuracy in prediction of CVST (AUROC = 0.809).