Distinct cell death markers identified in critical care patient survivors diagnosed with sepsis.

Sepsis is an abnormal immune response to infection characterized by an overwhelming systemic inflammation and cell death. Non-apoptotic cell death pertaining to pyroptosis, necroptosis and autophagy contribute to sepsis pathogenesis apart from classical apoptotic cell death. The objective of the current study is to investigate the presence of molecular markers of relevance to apoptotic and non-apoptotic cell death in control healthy subjects and septic patient survivors. Sepsis survivors (N = 24) and healthy human volunteers (N = 16) [40 total subjects] were recruited into the study. Clinical intervention included antibiotic treatment regimen administered to patients upon clinical diagnosis of sepsis followed by blood draw 18-24 hr post-antibiotic dose. Serum samples analyzed by enzyme-linked immunosorbent assay (ELISA) and peripheral blood mononuclear cells (PBMCs) by flow cytometry analysis for identification of cell death markers. Cell death markers analyzed by ELISA and flow cytometry included caspase-1, caspase-3, MLKL, RIPK3, p62 and LC3B. Serum and peripheral blood mononuclear cells (PBMCs) of septic survivors and healthy controls analyzed for the presence of distinct cell death markers. Markers of relevance to apoptosis (caspase-3), pyroptosis (caspase-1), necroptosis (MLKL) and autophagy (p62 and LC3B) were compared between septic survivors and healthy controls. ELISA analysis suggested significant alterations in the serum levels of non-apoptotic cell death markers, caspase-1 and p62/SQSTM1, in septic survivors compared to healthy controls (p < 0.05). There was no significant difference in the serum levels of caspase-3 and MLKL between septic survivors and healthy control subjects (p> 0.05). Intracellular caspase-1 levels did not show any significant alterations between septic survivors and healthy control subjects (p > 0.05). Flow cytometry analysis suggested significant increase in the intracellular expression of caspase-3, MLKL and its associated kinase RIPK3, and p62/SQSTM1 (p < 0.05) in sepsis patient survivors when compared to healthy human subjects. The current observational study identified significantly elevated levels of non-apoptotic cell death markers in sepsis patients compared to healthy controls. Noteworthy observation is the significant modulation of non-apoptotic cell death markers in serum samples derived from septic survivors post-antibiotic administration compared to healthy control subjects. Preliminary results serve as a basis for further mechanistic investigations to elucidate the role of distinct cell death markers in the prediction of clinical outcomes in sepsis.

Active pulmonary tuberculosis presenting with acute respiratory failure.

Four patients with active pulmonary tuberculosis (PTB) presenting with respiratory failure are reported here. Bronchogenic PTB, simulating an acute febrile illness or diffuse interstitial lung disease with short duration of symptoms, as a cause of acute respiratory failure is less recognized. If diagnosed and treated early, it has good prognosis. Three of the four patients presented here had an acute presentation with fever, dyspnoea, and hypoxemia with diffuse infiltrative lesions on radiography, and the other younger patient presented predominantly with lobar consolidation. These patients presenting with respiratory failure required intensive care management, and a diagnosis was made with bronchoalveolar lavage fluid and transbronchial lung biopsy. All four patients promptly received antitubercular therapy, showed clinicoradiological improvement, and were stable at 1 year follow up.

Nasal application of petrolatum ointment - A silent cause of exogenous lipoid pneumonia: Successfully treated with prednisolone.

We report a case of exogenous lipoid pneumonia from chronic, extranasal use of petrolatum ointment (Vicks VapoRub in this case) for nasal decongestion in a young woman, presenting with cough, dyspnea and fever. Exogenous Lipoid pneumonia is a rare condition, underdiagnosed and is more prevalent in adults. Usually asymptomatic and diagnosed while evaluating predisposed patients who become clinically unstable or an abnormal lung shadow or during evaluation of rhinobronchial allergy. It is rarely reported from chronic use of petrolatum ointment extranasally and was diagnosed by transbronchial biopsy in the present case. She was found, retrospectively, to have been using petrolatum ointment, as an extranasal application since more than a year at bedtime. She didn't give history of using any other oil-based nasal topical vasoconstrictor preparations for sinusitis. Our patient was managed with discontinuation of further use of the petrolatum ointment and treatment with prednisolone apart from her regular treatment for chronic rhinobronchial allergy. Patient is stable without any further radiological deterioration during follow-up of one year.