Clinical characteristics of non-sleepy obstructive sleep apnea patients: a study in a tertiary care sleep clinic in India.

Obstructive sleep apnea (OSA) encompasses a diverse population, manifesting with or without symptoms of excessive daytime sleepiness. There is contention surrounding the significance of non-sleepy OSA within clinical contexts and whether routine treatment is warranted. This study aims to evaluate epidemiological and clinical distinctions between sleepy and non-sleepy OSA patients. A retrospective analysis was conducted on consecutive patients undergoing polysomnography for OSA assessment at tertiary care hospitals between 2018 and 2023. For 176 of 250 patients, complete polysomnography records with OSA diagnoses were available. Non-sleepy OSA was defined when a patient had an Epworth sleepiness scale score <10 and polysomnography demonstrated an apnea hypopnea index ≥5/hour. Non-sleepy OSA patients were matched with sleepy OSA patients in terms of age and gender distribution (mean age 51.24±13.25 years versus 50.9±10.87 years, male 70.4% versus 73.3%). The sensitivity of STOP-BANG≥3 for the non-sleepy OSA group was 87.7%, 89.3%, and 95.2% for any OSA severity, moderate to severe OSA, and severe OSA, respectively, while the corresponding sensitivity for the sleepy OSA group was 96.5%, 98.6%, and 100% for any OSA severity, moderate to severe OSA, and severe OSA, respectively. A novel symptom scoring tool, HASSUN (hypertension, nocturnal apneas, snoring, sleep disturbance, unrefreshing sleep, and nocturia), demonstrated a sensitivity of over 90% for all severity categories of OSA in both non-sleepy and sleepy OSA groups. The prevalence of cardiovascular and metabolic comorbidities did not significantly differ between non-sleepy and sleepy OSA patients. The physiological parameters, including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC ratio, arterial partial pressure of oxygen, and bicarbonate at baseline, were comparable between the two groups. To conclude, non-sleepy OSA patients are less obese, exhibit fewer symptoms, and have less severe OSA in comparison to sleepy OSA. Non-sleepy OSA patients display a similar likelihood of cardiovascular and metabolic comorbidities compared to sleepy OSA patients. Further investigations are warranted to elucidate the mechanisms underlying cardiovascular metabolic comorbidities in non-sleepy OSA patients. The proposed HASSUN scoring tool for non-sleepy OSA screening necessitates validation in future studies.

Thoracoscopic blood patch instillation for persistent air leak in pneumothorax: a case series and systematic review.

Persistent air leaks in patients with pneumothorax can lead to significant morbidity. If a patient with persistent air leak is medically unfit for thoracic surgery, medical pleurodesis via chest tube or thoracoscopy is either an option. Thoracoscopy offers the advantage of visualizing the site of the air leak and enabling direct instillation of the pleurodesis agent or glue at that location. Autologous blood patch instillation via chest tube has been reported to be a cheap and very effective technique for the management of persistent air leaks. However, thoracoscopic blood patch instillation has not been reported in the literature. We report two cases of secondary spontaneous pneumothorax in which patients had persistent air leaks for more than seven days and were subjected to thoracoscopy to locate the site of the leak. In the same sitting, 50 mL of autologous blood patch was instilled directly at the leak site. Post-procedure, the air leak subsided in both patients, and the chest tube was removed with complete lung expansion. We also conducted a systematic review of the use of medical thoracoscopic interventions for treating persistent air leaks.

Comparative yield of transbronchial cryo-nodal biopsy, transbronchial intra-nodal forceps biopsy, and transbronchial needle aspiration for mediastinal lesions at a tertiary care center in India (COLD-FORCEPS study).

Endobronchial ultrasound (EBUS) guided mediastinal cryobiopsy, and intranodal forceps biopsy are newer modalities for sampling mediastinal lymph nodes. The data regarding the diagnostic yield of both modalities is scarce. Patients were recruited retrospectively from our existing database. Patients who had undergone both an EBUS guided mediastinal cryobiopsy and an intranodal forceps biopsy were enrolled in the study. The final diagnosis was made with a clinical-pathological-radiological assessment and clinico-radiological follow-up after one month. A total of 34 patients were enrolled in the study who had undergone both EBUS guided mediastinal cryobiopsy and intranodal forceps biopsy and had complete data available, including 1-month follow-up data. The sample adequacy rate of EBUS-transbronchial needle aspiration (EBUS-TBNA), EBUS-TBNA with mediastinal cryobiopsy, and EBUS-TBNA with intranodal forceps biopsy was 94.11%, 97.05%, and 94.11%, respectively (p=0.56). The diagnostic yield achieved in EBUS-TBNA, EBUS-TBNA with mediastinal cryobiopsy, and EBUS-TBNA with intranodal forceps biopsy was 73.52%, 82.35%, and 79.41%, respectively (p=0.38). No major complications were seen in any patient. To conclude, adding EBUS guided mediastinal cryobiopsy and intranodal forceps biopsy to EBUS-TBNA may not be superior to routine EBUS-TBNA.

Comparison of immediate withdrawal and stepwise reduction in duration of non-invasive ventilation in chronic obstructive pulmonary disease patients presenting with acute hypercapnic respiratory failure.

There is no universally acceptable protocol for the withdrawal of non-invasive ventilation (NIV) in chronic obstructive pulmonary disease (COPD) patients presenting with acute hypercapnic respiratory failure (AHcRF). This study was carried out to evaluate immediate against stepwise reduction in NIV. Sixty COPD patients with AHcRF who were managed with NIV were randomized into two groups - immediate NIV withdrawal (Group A), and stepwise reduction of NIV duration (Group B). The rate of successful NIV withdrawal, time to recurrence of hypercapnic respiratory failure, total duration of NIV use, and hospital length of stay (LOS), were compared among the 2 groups. NIV was successfully withdrawn in 51/60 (85%) patients. NIV was successfully withdrawn in 24/30 (80%) patients in Group A and 27/30 (90%) patients in Group B (p=0.472). The total duration of NIV use was significantly lower in Group A (38.97±17 hours) as compared to Group B (64.3±7.74 hours) (p<0.0001). The hospital LOS was significantly lower in group A (5.8±1.6 days) as compared to Group B (7.7±0.61 days) (p<0.0001). To conclude, immediate withdrawal of the NIV after recovery of respiratory failure among patients with exacerbation of COPD is feasible and does not increase the risk of weaning failure.

Tumor cell phagocytosis (cannibalism) in lung cancer: possible biomarker for tumor immune escape and prognosis.

BACKGROUND: Tumor cell phagocytosis (cannibalism) is rarely seen in lung carcinomas. Little is known about its underlying cellular pathogenesis and associated significance as tumor immune escape mechanism. METHODOLOGY: The cases of lung cancer diagnosed at department of Pathology, VPCI over 13-year period, 2007-2020 (n = 350) were retrospectively reviewed. The cases displaying cannibalism were correlated with their tumor morphology, coexisting inflammation, patient age at presentation, sex, stage/grade, and smoking status. RESULTS: Cannibalism was identified in 10/350 (2.86%) cases of lung cancer. 9/10 (90%) were males and 1/10 (10%) was female. These patients ranged from 48-71 years of age and presented with history of chest pain, anorexia and weight loss. History of smoking was seen in 9/10 (90%) cases while 10% were non-smokers. Mass lesions were seen on CT scan and CT-guided fine needle aspiration cytology (FNAC) was performed. Cytopathology revealed squamous cell carcinoma (5/10, 50%), adenocarcinoma-3/10 (30%), adenosquamous carcinoma (1/10, 10%), and non small cell lung carcinoma (1/10, 10%). No association with small cell carcinoma was seen in our study. Background inflammation and infiltration of acute on chronic inflammatory infiltrate were seen in 6/10 or 60% cases. CONCLUSION: Lung cancers rarely show cannibalism, a tumor immune escape mechanism, even in advanced stage. This phenomenon correlates with squamous cell and adenocarcinoma morphology, tumor associated inflammatory infiltrate, and smoking status. It may be considered as a possible biomarker for tumor immune escape and poor prognosis.

Role of Emergency Automated Red Cell Exchange in Sickle Cell Crisis: A Case Report.

For many years main stay of treatment for sickle cell anaemia was transfusion therapy. But repeated transfusions put the patient at risk of iron overload. Automated red cell exchange is an evolving and newer technique which rapidly removes the sickle cells and has benefit in decreasing sickle cell load and related complications. Red cell exchange is a therapeutic procedure in which the patient's whole blood is processed centrifugally in cell separator. Patient's red cells are separated from other blood components and removed and replaced with donor red cells and colloids. We report our first experience of automated red cell exchange in 24-year-old female diagnosed case of sickle cell anaemia presented to us with acute chest syndrome with septic shock. Red cell exchange was planned to tide over the acute sickle cell crisis and provide symptomatic improvement. We also highlight that compound heterozygous thalassaemia could be associated with sickle cell disease which could make the diagnosis difficult. New generation automated Apheresis equipment's provides better monitoring of the procedure that can be useful in severely ill patients also.

Diagnostic and Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Early and Late Phase of Sepsis.

OBJECTIVE: Early diagnosis of sepsis is necessary to decrease morbidity and mortality. This study aims to evaluate neutrophil-to-lymphocyte ratio (NLR) as diagnostic and prognostic of early and late phase of sepsis. METHODS: It was a prospective, observational study, conducted in Intensive Care and High Dependency Unit (Daycare) of the Department of Pulmonary and Critical Care Medicine (tertiary care center), Rohtak, from January 2017 to December 2017. A total of 56 cases of newly diagnosed cases of sepsis were included in the study and 20 healthy adults were taken as controls. Daily NLR was calculated in cases till the primary outcome. RESULTS: The results suggested that NLR seems to have promising role as diagnostic and prognostic marker (with P = 0.001 and P = 0.045, respectively) in sepsis. CONCLUSION: The study suggests that NLR can be a useful diagnostic and prognostic marker in sepsis.

A cellular restriction dictates the permissivity of nondividing monocytes/macrophages to lentivirus and gammaretrovirus infection.

Primate lentiviruses, including HIV-1, transduce terminally differentiated, nondividing myeloid cells; however, these cells are refractory to infection by gammaretroviruses such as murine leukemia virus (MLV). Here, we present evidence that a cellular restriction is the obstacle to transduction of macrophages by MLV. Neutralization of the restriction by Vpx, a primate lentiviral protein previously shown to protect primate lentiviruses from a macrophage restriction, rendered macrophages permissive to MLV infection. We further demonstrate that this restriction prevents transduction of quiescent monocytes by HIV-1. Monocyte-HeLa heterokaryons were resistant to HIV-1 infection, while heterokaryons formed between monocytes and HeLa cells expressing Vpx were permissive to HIV-1 infection. Encapsidation of Vpx within HIV-1 virions conferred the ability to infect quiescent monocytes. Collectively, our results indicate that the relative ability of lentiviruses and gammaretroviruses to transduce nondividing myeloid cells is dependent upon their ability to neutralize a cellular restriction.

Mutation of critical serine residues in HIV-1 matrix result in an envelope incorporation defect which can be rescued by truncation of the gp41 cytoplasmic tail.

The human immunodeficiency virus type 1 (HIV-1) matrix (MA) domain is involved in both early and late events of the viral life cycle. Simultaneous mutation of critical serine residues in MA has been shown previously to dramatically reduce phosphorylation of MA. However, the role of phosphorylation in viral replication remains unclear. Viruses harboring serine to alanine substitutions at positions 9, 67, 72, and 77 are severely impaired in their ability to infect target cells. In addition, the serine mutant viruses are defective in their ability to fuse with target cell membranes. Interestingly, both the fusion defect and the infectivity defect can be rescued by truncation of the long cytoplasmic tail of gp41 envelope protein (gp41CT). Sucrose density gradient analysis also reveals that these mutant viruses have reduced levels of gp120 envelope protein incorporated into the virions as compared to wild type virus. Truncation of the gp41CT rescues the envelope incorporation defect. Here we propose a model in which mutation of specific serine residues prevents MA interaction with lipid rafts during HIV-1 assembly and thereby impairs recruitment of envelope to the sites of viral budding.

Primate lentiviral Vpx commandeers DDB1 to counteract a macrophage restriction.

Primate lentiviruses encode four "accessory proteins" including Vif, Vpu, Nef, and Vpr/Vpx. Vif and Vpu counteract the antiviral effects of cellular restrictions to early and late steps in the viral replication cycle. We present evidence that the Vpx proteins of HIV-2/SIV(SM) promote virus infection by antagonizing an antiviral restriction in macrophages. Fusion of macrophages in which Vpx was essential for virus infection, with COS cells in which Vpx was dispensable for virus infection, generated heterokaryons that supported infection by wild-type SIV but not Vpx-deleted SIV. The restriction potently antagonized infection of macrophages by HIV-1, and expression of Vpx in macrophages in trans overcame the restriction to HIV-1 and SIV infection. Vpx was ubiquitylated and both ubiquitylation and the proteasome regulated the activity of Vpx. The ability of Vpx to counteract the restriction to HIV-1 and SIV infection was dependent upon the HIV-1 Vpr interacting protein, damaged DNA binding protein 1 (DDB1), and DDB1 partially substituted for Vpx when fused to Vpr. Our results indicate that macrophage harbor a potent antiviral restriction and that primate lentiviruses have evolved Vpx to counteract this restriction.

Phosphoprotein P of Rinderpest virus binds to plus sense leader RNA: regulation by phosphorylation.

The negative sense genome RNA of Rinderpest virus, a Paramyxoviridae, is encapsidated with the nucleocapsid protein N and serves as a template for the viral RNA dependent RNA polymerase for transcription and replication. The viral RNA polymerase consists of the large protein L and the phosphoprotein P functioning as the P-L complex. We provide in this report, evidences for specific binding of P protein of Rinderpest virus to the plus sense leader RNA depending on its phosphorylation status. We have also demonstrated that P protein is released from the le RNA:P protein complex upon phosphorylation in vitro. Finally, we have identified that the C-terminal 358-389 amino acid residues of P protein is involved in le RNA binding. The leader RNA binding may signify a hitherto unidentified role for P protein in the viral RNA synthesis. Moreover, our results indicate a possible role for P protein in the transcription-replication switch through leader RNA binding.

Cellular casein kinase II-mediated phosphorylation of rinderpest virus P protein is a prerequisite for its role in replication/transcription of the genome.

Phosphoprotein P of rinderpest virus (RPV), when expressed in E. coli, is present in the unphosphorylated form. Bacterially expressed P protein was phosphorylated by a eukaryotic cellular extract, and casein kinase II (CK II) was identified as the cellular kinase involved in phosphorylation. In vitro phosphorylation of P-deletion mutants identified the N terminus as a phosphorylation domain. In vivo phosphorylation of single or multiple serine mutants of P protein identified serine residues at 49, 88 and 151 as phospho-acceptor residues. The role of P protein phosphorylation in virus replication/transcription was evaluated using the RPV minigenome system and replication/transcription of a reporter gene in vivo. P protein phosphorylation was shown to be essential for in vivo replication/transcription since phosphorylation-null mutants do not support expression of a reporter gene. Transfection of increased amounts of phosphorylation-null mutant did not support minigenome replication/transcription in vivo.

Role of human immunodeficiency virus type 1 matrix phosphorylation in an early postentry step of virus replication.

The matrix domain (MA) is important for targeting of human immunodeficiency virus type 1 Gag assembly to the plasma membrane, envelope incorporation into virions, preintegration complex import into the nucleus, and nuclear export of viral RNA. Myristylation and phosphorylation are key regulatory events for MA function. Previous studies have indicated that MA phosphorylation at serine (Ser) residues is important for viral replication. This study defines the molecular mechanisms of virus particle assembly and infectivity through a detailed study of the role of MA serine phosphorylation. We show that the combined mutation of Ser residues at positions 9, 67, 72, and 77 impairs viral infectivity in dividing and nondividing cells, although the assembly of these Ser mutant viruses is comparable to that of wild-type virus. This defect can be rescued by pseudotyping these mutant viruses with vesicular stomatitis virus G protein, suggesting that these serine residues are critical in an early postentry step of viral infection. The phosphorylation level of MA in defective mutant viruses was severely reduced compared to that of the wild type, suggesting that phosphorylation of Ser-9, -67, -72, and -77 is important for an early postentry step during virus infection.