Antioxidant therapies for obstructive sleep apnea: A systematic review and meta-analysis.

PURPOSE: Obstructive sleep apnea (OSA) is a common clinical problem that is associated with adverse cardiovascular outcomes attributed to the oxidative stress due to sympathetic overstimulation. Treatment approaches targeting oxidative stress have been tried by multiple investigators. This systematic review and meta-analysis evaluated the efficacy and safety of such approaches. METHODS: Pubmed and Embase databases were searched for human studies evaluating the utility of antioxidant therapies in patients with OSA. RESULTS: A total of six studies (five randomized trials and one case-control study) were included, including 160 patients with OSA using N-acetyl cysteine, vitamin C, carbocysteine, superoxide dismutase, vitamin E, allopurinol, and their combinations. There was a significant improvement in flow-mediated dilatation (FMD) following antioxidants, with the pooled effect being 2.16 % (95% CI 1.65-2.67) using the random-effects model (I2 = 0% and p<0.001). It was also associated with a significant reduction in malondialdehyde levels and an increase in reduced glutathione (GSH) levels. There was also a significant improvement in the Epworth sleepiness scale, oxygen desaturation index, and minimum oxygen saturation during sleep without any significant adverse effects. CONCLUSION: Antioxidant therapy in patients with OSA is associated with improved endothelial function, reduced oxidative stress, and improved sleep parameters. These results call for future multicentre studies with longer follow-ups to assess the utility of antioxidant therapy in patients with OSA.

A multicentre, double-blind, placebo-controlled randomized trial of Mycobacterium w in critically ill patients with COVID-19 (ARMY-2).

BACKGROUND: Mycobacterium w (Mw), an immunomodulator, resulted in better clinical status in severe coronavirus infectious disease 19 (COVID-19) but no survival benefit in a previous study. Herein, we investigate whether Mw could improve clinical outcomes and survival in COVID-19. MATERIALS AND METHODS: In a multicentric, randomized, double-blind, parallel-group, placebo-controlled trial, we randomized hospitalized subjects with severe COVID-19 to receive either 0.3 mL/day of Mw intradermally or a matching placebo for three consecutive days. The primary outcome was 28-day mortality. The co-primary outcome was the distribution of clinical status assessed on a seven-point ordinal scale ranging from discharged (category 1) to death (category 7) on study days 14, 21, and 28. The key secondary outcomes were the change in sequential organ failure assessment (SOFA) score on days 7 and 14 compared to the baseline, treatment-emergent adverse events, and others. RESULTS: We included 273 subjects (136 Mw, 137 placebo). The use of Mw did not improve 28-day survival (Mw vs. placebo, 18 [13.2%] vs. 12 [8.8%], P = 0.259) or the clinical status on days 14 (odds ratio [OR], 1.33; 95% confidence intervals [CI], 0.79-2.3), 21 (OR, 1.49; 95% CI, 0.83-2.7) or 28 (OR, 1.49; 95% CI, 0.79-2.8) between the two study arms. There was no difference in the delta SOFA score or other secondary outcomes between the two groups. We observed higher injection site reactions with Mw. CONCLUSION: Mw did not reduce 28-day mortality or improve clinical status on days 14, 21 and 28 compared to placebo in patients with severe COVID-19. [Trial identifier: CTRI/2020/04/024846].

Association of Leukocyte Subpopulations Identified by Flow Cytometry with Outcomes of Sepsis in a Respiratory Intensive Care Unit: An Observational Study.

INTRODUCTION: The dysregulated host immune response in sepsis is orchestrated by peripheral blood leukocytes. This study explored the associations of the peripheral blood leukocyte subpopulations with early clinical deterioration and mortality in sepsis. METHODS: We performed a prospective observational single-center study enrolling adult subjects with sepsis within 48 h of hospital admission. Peripheral blood flow cytometry was performed for the patients at enrolment and after 5 days. The primary outcome was to explore the association between various leukocyte subpopulations at enrolment and early clinical deterioration [defined as an increase in the sequential organ failure assessment (SOFA) score between enrolment and day 5, or death before day 5]. Other pre-specified outcomes explored associations of leukocyte subpopulations at enrolment and on day 5 with in-hospital mortality. RESULTS: A total of 100 patients, including 47 with septic shock were enrolled. The mean (SD) age of the patients was 53.99 (14.93) years. Among them, 26 patients had early clinical deterioration, whereas 41 died during hospitalization. There was no significant association between the leukocyte subpopulations at enrolment and early clinical deterioration on day 5. On multivariate logistic regression, a reduced percentage of CD8 + CD25+ T-cells at enrolment was associated with in-hospital mortality [odds ratio (OR), 0.82 (0.70-0.97); p-value = 0.02]. A reduced lymphocyte percentage on day 5 was associated with in-hospital mortality [OR, 0.28 (0.11-0.69); p-value = 0.01]. In a post-hoc analysis, patients with "very early" deterioration within 48 h had an increased granulocyte CD64 median fluorescent intensity (MFI) [OR, 1.07 (1.01-1.14); p-value = 0.02] and a reduced granulocyte CD16 MFI [OR, 0.97 (0.95-1.00); p-value = 0.04] at enrolment. CONCLUSIONS: None of the leukocyte subpopulations showed an association with early clinical deterioration at day 5. Impaired lymphocyte activation and lymphocytopenia indicative of adaptive immune dysfunction may be associated with in-hospital mortality.

Enhancement of Curcumin's Anti-Psoriatic Efficacy via Formulation into Tea Tree Oil-Based Emulgel.

Psoriasis is a chronic inflammatory skin disease characterized by the hyperproliferation and aberrant differentiation of epidermal keratinocytes. It is a debilitating condition that can cause significant physical and emotional distress. Natural anti-psoriatic agents have been investigated as alternatives to conventional allopathic medications, as they have notable limitations and drawbacks. Curcumin and tea tree oil are cost-efficient and effective anti-inflammatory medicines with less adverse effects compared to synthetic psoriasis medications. Our research endeavors to harness the therapeutic potential of these natural compounds by developing an herbal anti-psoriatic topical drug delivery system. This novel method uses curcumin and tea tree oil to create a bi-phasic emulgel drug delivery system. Formulations F1 (gel) and F2 (emulgel) have high drug content percentages of 84.2% and 96.7%, respectively. The emulgel showed better spreadability for cutaneous applications, with a viscosity of 92,200 ± 943 cp compared to the gel's 56,200 ± 1725 cp. The emulgel released 94.48% of the drugs, compared to 87.58% for the gel. These formulations conform to the zero-order and Higuchi models, and their stability over a three-month period is crucial. In vivo, the emulgel healed psoriasis symptoms faster than the usual gel. The gathered results confirmed the emulgel's potential as a drug delivery method, emphasizing the complementary benefits of tea tree oil and curcumin as an effective new therapy for psoriasis.

An overview of unresolved issues in the perioperative management of liver transplant patients.

Over the past decade, the field of solid organ transplantation has undergone significant changes, with some of the most notable advancements occurring in liver transplantation. Recent years have seen substantial progress in preoperative patient optimization protocols, anesthesia monitoring, coagulation management, and fluid management, among other areas. These improvements have led to excellent perioperative outcomes for all surgical patients, including those undergoing liver transplantation. In the last few decades, there have been numerous publications in the field of liver transplantation, but controversies related to perioperative management of liver transplant recipients persist. In this review article, we address the unresolved issues surrounding the anesthetic management of patients scheduled for liver transplantation.

Transoesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-B-FNA) for left adrenal gland (LAG) sampling: A report of three cases with a review of the literature.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a standard-of-care modality for evaluating mediastinal lymph nodes and masses. The EBUS bronchoscope may also be introduced through the oesophageal route to perform sampling of accessible lesions, a technique described as transoesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-B-FNA). Because of the central oesophageal approach, EUS-B-FNA provides easy access to the left para-tracheal, subcarinal and para-oesophageal lymph nodes. In addition, the left adrenal gland (LAG) can also be imaged and sampled during the EUS-B-FNA procedure. In patients with suspected lung cancer, accurate staging is essential. Adrenal metastasis is relatively common and may often be a solitary metastatic site. We describe three cases where EUS-B-FNA was performed to safely sample the enlarged LAG in suspected lung cancer. We also review the literature on the performance characteristics of EUS-B-FNA for LAG aspiration.

Prevalence of chronic obstructive pulmonary disease in Indian nonsmokers: a systematic review & meta-analysis.

INTRODUCTION: Nonsmokers with chronic obstructive pulmonary disease (COPD) are neglected despite constituting half of all cases in studies from the developed world. Herein, we systematically reviewed the prevalence of COPD among nonsmokers in India. CONTENT: We searched Embase, Scopus, and PubMed databases for studies examining the prevalence of COPD among nonsmokers in India. We used the Joanna Briggs Institute (JBI) checklist to assess included studies' quality. Meta-analysis was performed using random-effects model. SUMMARY: Seven studies comprising 6,903 subjects were included. The quality of the studies ranged from 5/9 to 8/9. The prevalence of COPD varied between 1.6 and 26.6 %. Studies differed considerably in demographics and biomass exposure profiles of subjects. Among the four studies that enrolled both middle-aged and elderly Indian nonsmokers not screened based on biomass fuel exposure, the pooled prevalence of COPD was 3 % (95 % CI, 2-3 %; I2=50.52 %, p=0.11). The pooled prevalence of COPD among biomass fuel-exposed individuals was 10 % (95 % CI, 2-18 %; I2=98.8 %, p<0.001). OUTLOOK: Limited evidence suggests a sizable burden of COPD among nonsmokers and biomass fuel-exposed individuals in India. More epidemiological studies of COPD in nonsmokers are needed from low and middle-income countries.

Perioperative management of a severely thrombocytopenic kidney transplant recipient using thromboelastography.

Perioperative transfusion of blood and blood products can be avoided or reduced with bedside real time monitoring of coagulation in patients at risk. Thromboelastography (TEG), is a point of care coagulation monitor to assess dynamic progress of clot formation. We report a case of 26 years old female patient with end-stage kidney disease (ESKD) who underwent living donor kidney transplantation at our institute. On preoperative work-up, her complete blood count revealed severe thrombocytopenia. Etiology of thrombocytopenia could not be established except past history of hemolysis, elevated liver enzymes, and low platelets syndrome in her last pregnancy. Perioperative transfusion of blood and blood products was guided with TEG and transplant was conducted successfully without any transfusion. In conclusion, severe thrombocytopenia in patients with ESKD enhances the risk of perioperative bleeding and related complications in already compromised coagulation system. Kidney transplant without pre-emptive transfusion could be possible with perioperative use of TEG.

Quality by design engineered, enhanced anticancer activity of temozolomide and resveratrol coloaded NLC and brain targeting via lactoferrin conjugation in treatment of glioblastoma.

The most dangerous type of high-grade astrocytoma is glioblastoma multiforme. The objective of the work was to engineer lactoferrin conjugated temozolomide and resveratrol co-loaded NLC for the treatment of glioblastoma using intranasal delivery for brain targeting. Synergistic activity of temozolomide and resveratrol was determined using combination index method and 1:1 ratio was selected. QbD approach was used to formulate and optimize NLC, with minimum particle size, maximum transmittance and entrapment efficiency using Central Composite Rotable Design (CCRD) method. The optimized LTR-NLC had desired average particle size (209.3 nm), narrow PDI along, high percentage transmittance (>95%) and better entrapment efficiency (95.26% of TEM and 87.59% of RES). From ex-vivo permeation studies it was found that the permeation at 24 h was 77.43 %, and 88.55 % from LTR-NLC and 25.76 % and 31.10% from suspension for resveratrol and temozolomide respectively. In comparison to drug suspension, NLC had nearly 3-fold increase in drug penetration. IC50 value was also significantly better in the groups treated with LTR-NLC. Hence it can be concluded that LTR-NLC may be an effective formulation for the treatment of glioblastoma, according to the findings of this investigation.

Basic spirometry and advanced pulmonary function tests - NATCON 2022.

At the 77th National Conference on Tuberculosis and Chest Diseases, which took place on February 27, 2023, a pre-conference workshop on Basic Spirometry and Advanced Pulmonary Function Tests was held under the auspices of NATCON-2022. With the assistance of highly experienced faculty who are national and international level experts in their fields, the workshop covered all important aspects of basic spirometry and advanced Pulmonary Function Tests.

Systematic review and meta-analysis of the prevalence of obstructive sleep apnea in Indian adults.

Obstructive sleep apnea (OSA) is a common sleep disorder associated with considerable morbidity. However, there is an underrepresentation of data from India and other developing countries in global reviews of OSA prevalence. This systematic review and meta-analysis examined the prevalence of OSA in India. The MEDLINE, Embase, and Scopus databases were searched for articles that reported the prevalence of OSA in the general Indian adult population using sleep studies. Eight studies were included comprising 11,009 subjects with mean age ranging from 35.5 to 47.8 years. On the Joanna Briggs Institute (JBI) checklist for prevalence studies, the study quality ranged from 3/9 to 9/9. Meta-analysis was performed using the random-effects model. The pooled prevalence of OSA (AHI ≥5 events/hour) was 11% overall (95% CI: 7%-15%; I2 = 98.0%, p<0.001), 13% in males (95% CI: 7%-18%; I2 = 96.0%, p<0.001), and 5% in females (95% CI: 3%-7%; I2 = 73.3%, p = 0.01). The pooled prevalence of moderate-to-severe OSA (AHI ≥15 events/hour) was 5% (95% CI: 2%-8%, I2 = 95.3%; p = 0.01). Based on these findings, approximately 104 million Indians of working age suffer from OSA, of whom 47 million have moderate-to-severe OSA. This represents a major public health problem in India with important implications for the global burden of the disease.

Guidelines for endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA): Joint Indian Chest Society (ICS)/Indian Association for Bronchology (IAB) recommendations.

Over the past decade, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become an indispensable tool in the diagnostic armamentarium of the pulmonologist. As the expertise with EBUS-TBNA has evolved and several innovations have occurred, the indications for its use have expanded. However, several aspects of EBUS-TBNA are still not standardized. Hence, evidence-based guidelines are needed to optimize the diagnostic yield and safety of EBUS-TBNA. For this purpose, a working group of experts from India was constituted. A detailed and systematic search was performed to extract relevant literature pertaining to various aspects of EBUS-TBNA. The modified GRADE system was used for evaluating the level of evidence and assigning the strength of recommendations. The final recommendations were framed with the consensus of the working group after several rounds of online discussions and a two-day in-person meeting. These guidelines provide evidence-based recommendations encompassing indications of EBUS-TBNA, pre-procedure evaluation, sedation and anesthesia, technical and procedural aspects, sample processing, EBUS-TBNA in special situations, and training for EBUS-TBNA.

A "Cool" extraction technique for difficult pediatric airway foreign bodies: Report of two cases.

Foreign body (FB) aspiration is a potentially life-threatening accident in children. Traditionally, rigid bronchoscopy has been the procedure of choice for FB removal, however it may miss distally lodged FBs. We report two pediatric cases with distal impacted FBs that could not be retrieved by rigid bronchoscopy (RB) and were mobilised using Fogarty balloon followed by flexible bronchoscopic cryoextraction. The advantage of a cryoprobe is lower risk of fragmentation of FB that may occur with forceps. Cryoextraction is particularly advantageous for removing water-containing FBs. In both patients, FB was removed more than 2 weeks following aspiration, leading to the formation of granulation tissue around the FB, which considerably hampered the process. Using a laryngeal mask airway to secure the airway, FB removal by flexible bronchoscopy may be a safe and effective technique in skilled hands, especially for FBs impacted in distal airways with granulation tissue where RB fails.

Association of air pollution and coronavirus disease 2019 (COVID-19) in India.

The COVID-19 pandemic has affected the world, leading to significant morbidity and mortality. Various meteorological parameters are considered essential for the viability and transmission of the virus. Multiple reports from various parts of the world suggest a correlation between the disease spread and air pollution severity. This study was carried out to identify the relationship between meteorological parameters, air pollution, and COVID-19 in New Delhi, one of the worst-affected states in India. We studied air pollution and meteorological parameters in New Delhi, India. We obtained data about COVID-19 occurrence, meteorological parameters, and air pollution indicators from various sources from Apr 1, 2020, till Nov 12, 2020. We performed correlational analysis and employed autoregressive distributed lag models (ARDLM) for identifying the relationship between COVID-19 cases with air pollution and meteorological parameters. We found a significant impact of PM 2.5, PM 10, and meteorological parameters on COVID-19. There was a significant positive correlation between daily COVID-19 cases and COVID-19-related deaths with PM2.5 and PM10 levels. Increasing temperature and windspeed were associated with a reduction in the number of cases while increasing humidity was associated with increased cases. This study demonstrated a significant association of PM2.5 and PM10 with daily COVID-19 cases and COVID-19-related mortality. This knowledge will likely help us prepare well for the future and implement air pollution control measures for other airborne disease epidemics.

Clinical Profile and Quality of Life of Patients With Post-pulmonary Tuberculosis Sequelae Presenting to a Tertiary Care Hospital.

Background and objective There is a dearth of studies on the clinical presentation of patients with post-pulmonary tuberculosis (PTB) sequelae and its impact on their quality of life (QoL). In light of this, we conducted this study to analyze the clinical profile and QoL in patients with post-PTB sequelae. Methods Patients with a history of treated PTB and evidence of radiological damage were enrolled prospectively from November 2018 till June 2020 to study their clinical profile and QoL as per the eligibility criteria. A detailed clinical history was taken along with posteroanterior-view chest X-rays and CT scans of the thorax with bronchial angiography in patients with hemoptysis. QoL was assessed using the Hindi version of St. George's Respiratory Questionnaire (SGRQ) for which permission was obtained from the St. George's University of London. SGRQ scores were calculated using score calculation algorithms (Microsoft Excel-based) and missing data imputation as recommended by its developer. Results A total of 174 patients were included in the analysis. The analyzed population was relatively younger (mean age: 44.27 years) with BMIs leaning toward the lower side of normal (median: 19.6 kg/m²); the majority of the patients were males (59%) and non-smokers (77%). PTB had been diagnosed clinico-radiologically in the majority (68%) of patients with non-compliance to antitubercular treatment (ATT) being reported by only 9% of patients. Multiple courses of ATT were received by about one-third of patients, mainly on a clinico-radiologic basis. Systemic hypertension (HTN) (11%) and diabetes mellitus (DM) (9%) were the most common comorbidities. The most common symptom complex found was cough, expectoration, and dyspnea (n=102, 59%). At least one incidence of massive hemoptysis was reported by 20% of patients. Bronchial artery embolization (BAE) was performed for moderate to massive hemoptysis in 26% of patients with a success rate of >90%. One-fifth of the study participants required hospitalization for exacerbation of respiratory symptoms with more than half of these (59%) requiring ventilatory support. Health-related QoL was significantly impaired as reflected by a median SGRQ total score of 45.53. The most affected domain of QoL was the activity domain (mean score: 45.47). Females had worse QoL as compared to males (p=0.0062), and so did underweight patients (p=0.048). The prolonged duration of the illness also significantly impaired the QoL (p<0.001, r=0.313). Conclusion The sequelae of PTB are under-recognized even among physicians and are frequently misdiagnosed as active PTB. The QoL is more severely affected due to residual damage. This study highlights the clinical profile of this patient population and underscores the need to recognize post-PTB sequelae as a separate entity. An important remedy to mitigate its long-term consequences is its inclusion and recognition in national and international TB guidelines to facilitate its early identification and promote further research to address its evidence-based management.

Lung cancer in Asian Indian females: Identification of disease-specific characteristics and outcome measures over a 12-year period.

Aim: Globally, the incidence of lung cancer amongst women appears to be increasing. We aimed to compare the socio-epidemiological and clinical characteristics of lung cancer amongst men and women from a large cohort at a tertiary care hospital in Northern India. Methods: Records of patients diagnosed with lung cancer between January 2008 and March 2020 were reviewed. Baseline epidemiological data, clinical characteristics, histologic profiles, treatment administered, and survival were compared between males and females. Results: A total of 2054 male and 438 female patients were included in analysis. Compared to males, female patients were younger [median age, 56 vs. 60 years, P < 0.001)], less likely to be working, less educated beyond secondary level and less likely to be smokers (29.1% vs. 84.9%, P < 0.0001). No difference in baseline performance status was observed. Females were more frequently diagnosed with adenocarcinoma (54.2% vs. 30.2%, P = <0.0001), stage IV disease (70.8% vs. 63%, P = 0.001), and had higher rate of EGFR mutation (37.2% vs. 21.5%, P < 0.0001). There was no difference in the proportion of females receiving cancer-specific therapy. Multivariate Cox proportional hazards model revealed higher progression-free survival [median 9.17 vs. 7.23 months; P = 0.007] and overall survival [median 13.80 vs. 9.10 months respectively, P = 0.001] amongst females compared to males. Conclusion: Amongst a large cohort of lung cancer, females demonstrated several distinct and characteristic demographics as well as disease-related features, especially better survival outcomes.

A review on electronic nose for diagnosis and monitoring treatment response in lung cancer.

Lung cancer is one of the common malignancies with high mortality rate and a poor prognosis. Most lung cancer cases are diagnosed at an advanced stage either due to limited resources of infrastructure, trained human resources, or delay in clinical suspicion. Low-dose computed tomography has emerged as a screening tool for lung cancer detection but this may not be a feasible option for most developing countries. Electronic nose is a unique non-invasive device that has been developed for lung cancer diagnosis and monitoring response by exhaled breath analysis of volatile organic compounds. The breath-print have been shown to differ not only among lung cancer and other respiratory diseases, but also between various types of lung cancer. Hence, we postulate that the breath-print analysis by electronic nose could be a potential biomarker for the early detection of lung cancer along with monitoring treatment response in a resource-limited setting. In this review, we have consolidated the current published literature suggesting the use of an electronic nose in the diagnosis and monitoring treatment response of lung cancer.

Temporal evolution of diaphragm thickness and diaphragm excursion among subjects hospitalized with COVID-19: A prospective observational study.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has an affinity for the angiotensin-converting enzyme 2 (ACE2) receptors, which are present abundantly on the diaphragm. This study aims to describe temporal changes in diaphragmatic thickness and excursion using ultrasonography in subjects with acute COVID-19. METHODS: This prospective observational study included adults hospitalized with COVID-19 in the past 48 hours. The diaphragm thickness at end-expiration (DTE), diaphragm thickening fraction (DTF), and diaphragm excursion during tidal breathing (DE) and maximal inspiration (DEmax) were measured using ultrasonography daily for 5 days. The changes in DTE, DTF, DE, and Demax from day 1 to day 5 were assessed. RESULTS: This study included 64 adults (62.5% male) with a mean (SD) age of 50.2 (17.5) years. A majority (91%) of the participants had mild or moderate illness. The median (IQR) DTE, DTF (%), DE and Demax on day 1 were 2.2 (1.9, 3.0) mm, 21.5% (14.2, 31.0), 19.2 (16.5, 24.0) mm, and 26.7 (22.0, 30.2) mm, respectively. On day 5, there was a significant reduction in the DTE (p=0.002) with a median (IQR) percentage change of -15.7% (-21.0, 0.0). The DTF significantly increased on day 5 with a median (IQR) percentage change of 25.0% (-19.2, 98.4), p=0.03. There was no significant change in DE and Demax from day 1 to day 5, with a median (IQR) percentage change of 3.6% (-5.2, 15) and 0% (-6.7, 5.9), respectively. CONCLUSIONS: Non-intubated patients with COVID-19 exhibited a temporal decline in diaphragm thickness with increase in thickening fraction over 5 days of hospital admission. Further research is warranted to assess the impact of COVID-19 pneumonia on diaphragmatic function.