Evaluating the Clinical Utility of Staged Bronchoalveolar Lavage (BAL) Fluid Analysis in Adolescent and Adult Acute Leukemia and Lymphoma Patients with Febrile Neutropenia and Lung Infiltrates

Introduction: Lung infiltrates(LI) are seen in 30-45% of the patients with Febrile neutropenia(FN) in haematological malignancies.In FN patients with LI, accurate/probable microbiological diagnosis is possible in only 30 % with conventional blood culture and serological tests. BAL increases the microbiological diagnostic yield. The battery of microbiological tests done in BAL fluid analysis is not uniform.We evaluated a staged approach while analysing the BAL fluid sample, in the first stage we performed the routine cultures and antigen-based tests and in patients with negative results, we performed Polymerase Chain Reaction(PCR) tests guided by the radiological findings. Methods: This was a prospective observational study initiated after Institutional ethics committee approval and conducted at Tata memorial centre,Mumbai between November 2018 and June 2020.BAL testing was done as per a standard protocol(Sampsonas et al.) in hemodynamically stable patients with Spo2 more than 90% and platelet count above 300x10 9/L.Samples were sent for gram stain & bacterial cultures, ziehl neelsen stain and cultures, fungal stain and cultures and Galactomannan (ELISA) and an extra sample was preserved in an EDTA vacutainer at 10-20 degree C. If none of the initial reports were positive, then stored BAL sample was sent for PCR testing guided by the radiology and clinical picture i.e., with nodular infiltrates(Bacteria,Nocardia,Aspergillus,Mucor,P.Jiroveci,Mycobacterium TB,Atypical Mycobacterium TB) and with diffuse micronodular infiltrates Viruses,Legionella,mycoplasma PCR tests were sent. The causal association of the isolated organism was defined as per AGIHO guidelines(G. Maschmeyer et al.) The Primary objective is proportion of patients with a confirmed microbiological diagnosis using staged BAL analysis. The Secondary Objectives are proportion of patients who had a change in antimicrobial therapy,Feasibility of doing a Bronchoscopy and Proportion of Patients who develop Major or Minor complications during procedure and the 4 and 12weeks Clinical and Radiological Outcomes. A sample size of 130 patients was required for incidence of 50%(40-60%) positivity with 10% variation at 95% confidence interval. Results: A total of 172 patients were eligible of which 50 patients are not enrolled due to physician discretion in 37 patients,9 lost for followup and 2 refused consent and one patient expired and one palliated and 122 patients are enrolled and of these BAL couldn't be done in 20 patients due to hypoxia,low platelets,poor GCS at the time of performing BAL and finally BAL is feasible in 83.6%(n=102/122) patients. Baseline characteristics of patients are mentioned in Table 1.Median age of the patients was 30 (15-65) years with 69.6% males (n=85/122). A confirmed microbiological diagnosis (G. Maschmeyer et al.) was established in 71.3%( 81 /122 ) of cases.Microbiological results are depicted in Table2. A change of antimicrobial based on BAL (addition and removal of antimicrobial) was done for 78 patients(63.8%) of which 42 had removal of antibacterial and 11 patients had removal of antifungals. Among 42 patients who had removal of antibiotics, by the end of 4weeks, 36(85.7%) had clinical response and 34 had radiological response,(4 died and 2 lost for followup). By the end of 12weeks, 31 patients had sustained clinical and radiological response (2 died, 2 lost to follow-up and 1 progressive disease). Among 11 patients with removal of antifungals 9 had clinical and radiological response by the end of 4weeks (1 died and 1 non responder) which was sustained at week 12. Complications of BAL One patient had a major complication (persistent hypoxia), while minor complications were recorded in 27/122 (22%) (Hypoxia-16, hypertension-8,tachycardia-3) during procedure and in 21/122 (17%) (Fever-8, bleeds-6, tachycardia-5,hypertension-2)upto 24 hours post procedure. Clinical and Radiological responses as per criteria( Figure 1) Conclusion: BAL fluid analysis improves the diagnostic yield in febrile neutropenia with lung infiltrates. This leads to a change in antimicrobials in a significant number of patients. It contributes to improved outcomes in this patient population. The test is feasible in a large majority, is safe and the staged approach helps in optimisation of resources. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Stroke vs. SIADH: A case of symptomatic hyponatremia secondary to SIADH in association with COVID-19 infection

A 66-year-old male with no known past medical history presented with history of two days of throbbing frontal headache associated with nausea, vomiting and left-sided facial droop. The patient also reported dizziness, subjective chills without cough, shortness of breath, or sputum production. Laboratory findings revealed elevated inflammatory markers but normal thyroid, kidney, and liver function tests. Initial sodium level was 126 mEq/L. Urine studies showed elevated urine osmolality of 647 mOsm/Kg and urine sodium level of 175 mEq/L, both suggestive of syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The TSH and ACTH stimulation tests both came back as normal. CT scan of the chest showed no evidence of lung infiltrates. Diffusion weighted MRI of the brain showed no evidence of acute or subacute CVA. SARS-CoV-2 nasal swab test was resulted positive. With these findings we diagnosed our patient with SIADH. Patient was initially started on 3% saline infusion for symptomatic hyponatremia. A fluid restricted diet was enforced. Patient was also started on salt tablets in order to increase solute intake. Sodium slowly corrected throughout the hospitalization. Of note, our patient never became hypoxic, neither did he show evidence of clinical pneumonia. A CT imaging of the chest showed no lung infiltrates, and an MRI of the brain was negative for any acute intracranial abnormalities. This case highlights the role of early recognition of SIADH in the setting of SARS-CoV-2 infection even in the absence of hypoxemia or lung pathology.

Diabetes and Covid-19 among hospitalized patients in Saudi Arabia: a single-centre retrospective study

Background Information on the clinical characteristics and outcomes of hospitalized Covid-19 patients with or without diabetes mellitus (DM) is limited in the Arab region. This study aims to fill this gap. Methods In this single-center retrospective study, medical records of hospitalized adults with confirmed Covid-19 [RT-PCR positive for SARS-CoV2] at King Saud University Medical City (KSUMC)-King Khaled University Hospital (KKUH), Riyadh, Saudi Arabia from May to July 2020 were analyzed. Clinical, radiological and serological information, as well as outcomes were recorded and analyzed. Results A total of 439 patients were included (median age 55 years; 68.3% men). The most prevalent comorbidities were vitamin D deficiency (74.7%), DM (68.3%), hypertension (42.6%) and obesity (42.2%). During hospitalization, 77 out of the 439 patients (17.5%) died. DM patients have a significantly higher death rate (20.5% versus 12.3%; p = 0.04) and lower survival time (p = 0.016) than non-DM. Multivariate cox proportional hazards regression model revealed that age [Hazards ratio, HR 3.0 (95% confidence interval, CI 1.7–5.3); p < 0.001], congestive heart failure [adjusted HR 3.5 (CI 1.4–8.3); p = 0.006], smoking [adjusted HR 5.8 (CI 2.0–17.2); p < 0.001], β-blocker use [adjusted HR 1.7 (CI 1.0–2.9); p = 0.04], bilateral lung infiltrates [adjusted HR 1.9 (CI 1.1–3.3); p = 0.02], creatinine > 90 µmol/l [adjusted HR 2.1 (CI 1.3–3.5); p = 0.004] and 25(OH)D < 12.5 nmol/l [adjusted HR 7.0 (CI 1.7–28.2); p = 0.007] were significant predictors of mortality among hospitalized Covid-19 patients. Random blood glucose ≥ 11.1 mmol/l was significantly associated with intensive care admission [adjusted HR 1.5 (CI 1.0–2.2); p = 0.04], as well as smoking, β-blocker use, neutrophil > 7.5, creatinine > 90 µmol/l and alanine aminotransferase > 65U/l. Conclusion The prevalence of DM is high among hospitalized Covid-19 patients in Riyadh, Saudi Arabia. While DM patients have a higher mortality rate than their non-DM counterparts, other factors such as old age, congestive heart failure, smoking, β-blocker use, presence of bilateral lung infiltrates, elevated creatinine and severe vitamin D deficiency, appear to be more significant predictors of fatal outcome. Patients with acute metabolic dysfunctions, including hyperglycemia on admission are more likely to receive intensive care.

Interstitial pneumonia with autoimmune features in a patient with melanoma differentiation-associated gene 5 (MDA5) antibody

Melanoma differentiation-associated gene 5 (MDA5) antibody, also known as anti-CADM140 antibody is recognised to be associated with rapidly progressive interstitial lung disease, which can be fatal within 3 months. It is also known to be associated with amyopathic dermatomyositis. We report a case of MDA5 antibody-associated interstitial pneumonia with autoimmune features, without cutaneous features of dermatomyositis, in a Sudanese patient with dual positive antibodies to Ro52. The patient notably had several features associated with poor prognosis, including age, high serum ferritin level, anti-Ro52 antibodies and progressive lung infiltrates during treatment.

Skin Manifestations in COVID-19: Prevalence and Relationship with Disease Severity

Background: Data on the clinical patterns and histopathology of SARS-CoV-2 related skin lesions, as well as on their relationship with the severity of COVID-19 are limited. Methods and Materials: Retrospective analysis of a prospectively collected cohort of patients with SARS-CoV-2 infection in a teaching hospital in Barcelona, Spain, from 1 April to 1 May 2020. Clinical, microbiological and therapeutic characteristics, clinicopathological patterns of skin lesions, and direct immunofluorescence and immunohistochemical findings in skin biopsies were analyzed. Results: Fifty-eight out of the 2761 patients (2.1%) either consulting to the emergency room or admitted to the hospital for COVID-19 suspicion during the study period presented COVID-19 related skin lesions. Cutaneous lesions could be categorized into six patterns represented by the acronym “GROUCH”: Generalized maculo-papular (20.7%), Grover’s disease and other papulo-vesicular eruptions (13.8%), livedo Reticularis (6.9%), Other eruptions (22.4%), Urticarial (6.9%), and CHilblain-like (29.3%). Skin biopsies were performed in 72.4%, including direct immunofluorescence in 71.4% and immunohistochemistry in 28.6%. Patients with chilblain-like lesions exhibited a characteristic histology and were significantly younger and presented lower rates of systemic symptoms, radiological lung infiltrates and analytical abnormalities, and hospital and ICU admission compared to the rest of patients. Conclusion: Cutaneous lesions in patients with COVID-19 appear to be relatively rare and varied. Patients with chilblain-like lesions have a characteristic clinicopathological pattern and a less severe presentation of COVID-19.