Risk factors, mortality, and predictors of survival in COVID-19-associated pulmonary mucormycosis: a multicentre retrospective study from India.

OBJECTIVES: To compare COVID-19-associated pulmonary mucormycosis (CAPM) with COVID-19-associated rhino-orbital mucormycosis (CAROM), ascertain factors associated with CAPM among patients with COVID-19, and identify factors associated with 12-week mortality in CAPM. METHODS: We performed a retrospective multicentre cohort study. All study participants had COVID-19. We enrolled CAPM, CAROM, and COVID-19 subjects without mucormycosis (controls; age-matched). We collected information on demography, predisposing factors, and details of COVID-19 illness. Univariable analysis was used to compare CAPM and CAROM. We used multivariable logistic regression to evaluate factors associated with CAPM (with hypoxemia during COVID-19 as the primary exposure) and at 12-week mortality. RESULTS: We included 1724 cases (CAPM [n = 122], CAROM [n = 1602]) and 3911 controls. Male sex, renal transplantation, multimorbidity, neutrophil-lymphocyte ratio, intensive care admission, and cumulative glucocorticoid dose for COVID-19 were significantly higher in CAPM than in CAROM. On multivariable analysis, COVID-19-related hypoxemia (aOR, 2.384; 95% CI, 1.209-4.700), male sex, rural residence, diabetes mellitus, serum C-reactive protein, glucocorticoid, and zinc use during COVID-19 were independently associated with CAPM. CAPM reported a higher 12-week mortality than CAROM (56 of the 107 [52.3%] vs. 413 of the 1356 [30.5%]; p = 0.0001). Hypoxemia during COVID-19 (aOR [95% CI], 3.70 [1.34-10.25]) and Aspergillus co-infection (aOR [95% CI], 5.40 [1.23-23.64]) were independently associated with mortality in CAPM, whereas surgery was associated with better survival. DISCUSSION: CAPM is a distinct entity with a higher mortality than CAROM. Hypoxemia during COVID-19 illness is associated with CAPM. COVID-19 hypoxemia and Aspergillus co-infection were associated with higher mortality in CAPM.

The mystery behind a 1000 day fever in a young male.

This case is of a 23 year old diabetic male who presented with fever and splenic lesions. He continued to have fever off and on over the next 3 years despite empirical antibiotics and anti-tubercular therapy. No definitive diagnosis could be made despite exhaustive investigations. Finally, a splenectomy resulted in sustained defervescence. The splenic histopathology showed caseating granulomas but aerobic cultures, Xpert MTB/Rif ULTRA, TB and fungal cultures were negative. A final diagnosis of splenic melioidosis was made based on the clinical features, radiology, histopathology, literature review and absence of an alternative diagnosis.

Definition, diagnosis, and management of COVID-19-associated pulmonary mucormycosis: Delphi consensus statement from the Fungal Infection Study Forum and Academy of Pulmonary Sciences, India.

COVID-19-associated pulmonary mucormycosis (CAPM) remains an underdiagnosed entity. Using a modified Delphi method, we have formulated a consensus statement for the diagnosis and management of CAPM. We selected 26 experts from various disciplines who are involved in managing CAPM. Three rounds of the Delphi process were held to reach consensus (≥70% agreement or disagreement) or dissensus. A consensus was achieved for 84 of the 89 statements. Pulmonary mucormycosis occurring within 3 months of COVID-19 diagnosis was labelled CAPM and classified further as proven, probable, and possible. We recommend flexible bronchoscopy to enable early diagnosis. The experts proposed definitions to categorise dual infections with aspergillosis and mucormycosis in patients with COVID-19. We recommend liposomal amphotericin B (5 mg/kg per day) and early surgery as central to the management of mucormycosis in patients with COVID-19. We recommend response assessment at 4-6 weeks using clinical and imaging parameters. Posaconazole or isavuconazole was recommended as maintenance therapy following initial response, but no consensus was reached for the duration of treatment. In patients with stable or progressive disease, the experts recommended salvage therapy with posaconazole or isavuconazole. CAPM is a rare but under-reported complication of COVID-19. Although we have proposed recommendations for defining, diagnosing, and managing CAPM, more extensive research is required.

A Difficult Case of Pyrexia of Unknown Origin.

This is the case of a 15-y-old boy who presented with fever and back pain with MRI features of spondylitis. A CT-guided vertebral biopsy showed acute and chronic inflammatory cells and grew Pseudomonas aeruginosa on aerobic culture. The child was treated for 2 wk with antibiotics with no response. Meanwhile, he developed new lung, liver, and splenic lesions on CT imaging. Empiric antitubercular therapy was then started and continued for 8 wk during which time there was progressive clinical deterioration. At this time the patient underwent bronchoscopy with lavage and endoscopic ultrasound-guided subcarinal lymph node and lung biopsy. The Xpert MTB/Rif ULTRA was "trace positive" in the bronchoscopic lavage with indeterminate rifampicin resistance, while it was negative in lymph node and lung biopsy. The lymph node and lung biopsy histopathology showed nonspecific inflammatory changes with no granulomas or malignant cells. In view of the positive Xpert ULTRA with indeterminate rifampicin resistance and no response to first-line drugs, treatment with second-line antitubercular drugs was initiated. The clinical condition continued to deteriorate; here the imaging findings were reviewed again and repeat aspiration cytology and biopsy from intra-abdominal nodes was carried out. This yielded the diagnosis of Hodgkin lymphoma. The patient had stage IVB disease. He responded well to standard chemotherapy and is currently in remission. The case illustrates the need to avoid empiric therapy, repeat invasive procedures if so needed, choose the site/method of biopsy appropriately and interpret results of investigations carefully when evaluating a patient with pyrexia of unknown origin.

Pathophysiology of COVID-19: Why Children Fare Better than Adults?

The world is facing Coronavirus Disease-2019 (COVID-19) pandemic, which is causing a large number of deaths and burden on intensive care facilities. It is caused by Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) originating in Wuhan, China. It has been seen that fewer children contract COVID-19 and among infected, children have less severe disease. Insights in pathophysiological mechanisms of less severity in children could be important for devising therapeutics for high-risk adults and elderly. Early closing of schools and day-care centers led to less frequent exposure and hence, lower infection rate in children. The expression of primary target receptor for SARS-CoV-2, i.e. angiotensin converting enzyme-2 (ACE-2), decreases with age. ACE-2 has lung protective effects by limiting angiotensin-2 mediated pulmonary capillary leak and inflammation. Severe COVID-19 disease is associated with high and persistent viral loads in adults. Children have strong innate immune response due to trained immunity (secondary to live-vaccines and frequent viral infections), leading to probably early control of infection at the site of entry. Adult patients show suppressed adaptive immunity and dysfunctional over-active innate immune response in severe infections, which is not seen in children. These could be related to immune-senescence in elderly. Excellent regeneration capacity of pediatric alveolar epithelium may be contributing to early recovery from COVID-19. Children, less frequently, have risk factors such as co-morbidities, smoking, and obesity. But young infants and children with pre-existing illnesses could be high risk groups and need careful monitoring. Studies describing immune-pathogenesis in COVID-19 are lacking in children and need urgent attention.

Neuroschistosomiasis: An Unusual Intracranial Space Occupying Lesion.

BACKGROUND: Neuroschistosomiasis is an uncommonly reported disease. CASE CHARACTERISTICS: An adolescent Indian boy residing in Kenya presented with headache, visual symptoms and seizures, with MRI showing space-occupying lesions in the occipital lobe and cerebellum. OBSERVATION: Brain biopsy was diagnostic of neuro-schistosomiasis; complete recovery was seen with praziquantel and corticosteroid therapy. MESSAGE: This case highlights the importance of considering epidemiology in differential diagnosis and establishing definitive diagnosis even if it is by invasive methods.

Surgical site infection rates in six cities of India: findings of the International Nosocomial Infection Control Consortium (INICC).

BACKGROUND: Surgical site infections are a threat to patient safety. However, in India, data on their rates stratified by surgical procedure are not available. METHODS: From January 2005 to December 2011, the International Nosocomial Infection Control Consortium (INICC) conducted a cohort prospective surveillance study on surgical site infections in 10 hospitals in 6 Indian cities. CDC National Healthcare Safety Network (CDC-NHSN) methods were applied and surgical procedures were classified into 11 types, according to the ninth edition of the International Classification of Diseases. RESULTS: We documented 1189 surgical site infections, associated with 28 340 surgical procedures (4.2%; 95% CI: 4.0-4.4). Surgical site infections rates were compared with INICC and CDC-NHSN reports, respectively: 4.3% for coronary bypass with chest and donor incision (4.5% vs 2.9%); 8.3% for breast surgery (1.7% vs 2.3%); 6.5% for cardiac surgery (5.6% vs 1.3%); 6.0% for exploratory abdominal surgery (4.1% vs 2.0%), among others. CONCLUSIONS: In most types of surgical procedures, surgical site infections rates were higher than those reported by the CDC-NHSN, but similar to INICC. This study is an important advancement towards the knowledge of surgical site infections epidemiology in the participating Indian hospitals that will allow us to introduce targeted interventions.

How good is compliance with surgical antibiotic prophylaxis guidelines in a tertiary care private hospital in India? A prospective study.

PURPOSE: There is a need to study compliance with surgical antibiotic prophylaxis guidelines in India. METHODS: In this prospective study, 100 consecutive surgical procedures performed at a tertiary care private hospital in Mumbai, India were observed. The choice of antibiotic, timing and duration of administration were recorded and compared to the hospital guidelines. RESULTS: Appropriateness of choice of antibiotic was seen in 68%, timing in 89%, dose in 75% and duration in 63% of cases. Hundred percent compliance to all criteria was observed in 52% of cases. The SSI rate was 3.3%. CONCLUSIONS: These compliance rates though suboptimal are similar to those reported in world literature. There is an urgent need to improve compliance with optimal surgical antibiotic prophylaxis guidelines so as to reduce risk of SSI and to prevent resistance and costs potentially associated with antibiotic misuse.

CNS germinoma in a boy with simple virilizing 21-hydroxylase deficiency and precocious puberty.

A 6 year-old boy presented with peripheral precocious puberty and was diagnosed as having simple virilizing 21-hydroxylase deficiency based on clinical features and elevated 17-hydroxyprogesterone levels on ACTH stimulation. He was managed with glucocorticoids and mineralocorticoids. Two years later he presented with features of CNS involvement in the form of seizures and raised intracranial pressure with rapid progression of puberty. Contrast enhanced CT scan of brain showed an intraventricular tumor with cerebrospinal fluid cytology suggestive of germinoma. Serum and CSF levels of human chorionic gonadotropin (hCG) and alphafetoprotein (AFP) were elevated, confirming the diagnosis of germinoma.