Role of bronchoalveolar lavage, transbronchial needle aspiration with bronchial biopsy correlation in lung tumours and immunohistochemistry wherever required

Background: Lung cancer is most frequently diagnosed major cancer in the world and the most common cause of cancer mortality worldwide. It comprises about 17% of the total new cancer cases in males and 23% of the total cancer deaths. The objectives of this study were to compare bronchial biopsy, BAL and TBNA in diagnosing lung malignancies and IHC wherever required.Methods: The study was conducted at Sher-i-Kashmir Institute of Medical Sciences Srinagar, India in the department of Pathology. It was a prospective study over a period of 1½ years from June 2015 to December 2016. All patients clinically/ radiologically suspected of lung malignancies who presented between June 2015 to December 2016 and underwent bronchial biopsy, BAL (washings) and TBNA were included in the study. The study included only those cases where BAL, TBNA and bronchial biopsy were done simultaneously.Results: Out of a total 117 clinically suspected cases of lung cancer, tumor was found in 103 cases (103/117) by biopsy, 51 cases by BAL (51/117) and 64 cases by TBNA (64/117). The total number of false positive cases and false negative cases by BAL were 6 and 58. Sensitivity of BAL was found to be 43.69% and specificity 57.14%. The total number of false positive cases and false negative cases by TBNA were 7 and 46. Sensitivity and specificity of TBNA was found to be 55.34% and 50.0%.Conclusions: Thus, in the present study yield of diagnosis was highest with the bronchoscopic biopsies and in maximum number of cases with a sensitivity of 88.034%, and specific histologic diagnosis was made by biopsies and IHC only. Though BAL and TBNA were inferior to bronchial biopsy in diagnosing lung malignancies but these were effective for peripheral lung malignancies and when the patient was at risk of haemorrhage

Cost of Severe Chronic Obstructive Pulmonary Disease Exacerbations in a High Burden Region in North India

Background: Data on costs of acute exacerbations of COPD (AECOPD) in low-income countries are sparse. We conducted a prospective survey to assess direct and indirect costs of severe AECOPD in a tertiary care setting in a high prevalence area of North India. Methods: We conducted face-to-face surveys using a semi-structured questionnaire among a convenience sample of 129 consenting patients admitted with AECOPD. Data were collected on out-of-pocket costs of hospitalization, consultation, medications, diagnostics, transportation, lodging, and missed work days for self and their attendants. Out-of-pocket costs were supplemented with World Health Organization-CHOICE estimates. Missed work-days were valued on per capita national income (Indian Rupees [INR] 68,748, US$1,145.8). Median total cost per exacerbation episode was INR 44,390 (Inter-quartile range [IQR]: INR 33,354–63,642; US$739.8, IQR: 555.9–1060.7). Hospital costs constituted the largest component of the costs (71%) followed by other costs directly borne by the patient himself (29%), medicine costs (14%), transportation charges (2%) and diagnostic tests (3%). Indirect costs to caregivers (median INR 1,544, IQR: INR 0–17,370 INR; US$25.7, IQR: US$0–289.5), calculated as financial loss due to missed work days, accounted for 4% of the total cost. Expenses were covered by family members in all but 11 patients. Conclusions: AECOPD in India are associated with substantial costs and strategies to reduce the burden of disease such as smoking cessation, influenza and pneumococcal vaccination, etc should be aggressively pursued

Bone Marrow Stromal Cell Transplantation Mitigates Radiation-Induced Gastrointestinal Syndrome in Mice

Nuclear accidents and terrorism presents a serious threat for mass casualty. While bone-marrow transplantation might mitigate hematopoietic syndrome, currently there are no approved medical countermeasures to alleviate radiation-induced gastrointestinal syndrome (RIGS), resulting from direct cytocidal effects on intestinal stem cells (ISC) and crypt stromal cells. We examined whether bone marrow-derived adherent stromal cell transplantation (BMSCT) could restitute irradiated intestinal stem cells niche and mitigate radiation-induced gastrointestinal syndrome.Autologous bone marrow was cultured in mesenchymal basal medium and adherent cells were harvested for transplantation to C57Bl6 mice, 24 and 72 hours after lethal whole body irradiation (10.4 Gy) or abdominal irradiation (16-20 Gy) in a single fraction. Mesenchymal, endothelial and myeloid population were characterized by flow cytometry. Intestinal crypt regeneration and absorptive function was assessed by histopathology and xylose absorption assay, respectively. In contrast to 100% mortality in irradiated controls, BMSCT mitigated RIGS and rescued mice from radiation lethality after 18 Gy of abdominal irradiation or 10.4 Gy whole body irradiation with 100% survival (p<0.0007 and p<0.0009 respectively) beyond 25 days. Transplantation of enriched myeloid and non-myeloid fractions failed to improve survival. BMASCT induced ISC regeneration, restitution of the ISC niche and xylose absorption. Serum levels of intestinal radioprotective factors, such as, R-Spondin1, KGF, PDGF and FGF2, and anti-inflammatory cytokines were elevated, while inflammatory cytokines were down regulated.Mitigation of lethal intestinal injury, following high doses of irradiation, can be achieved by intravenous transplantation of marrow-derived stromal cells, including mesenchymal, endothelial and macrophage cell population. BMASCT increases blood levels of intestinal growth factors and induces regeneration of the irradiated host ISC niche, thus providing a platform to discover potential radiation mitigators and protectors for acute radiation syndromes and chemo-radiation therapy of abdominal malignancies

Common, Intermediate and Well-Documented HLA Alleles in World Populations: CIWD Version 3.0.0

A catalog of common, intermediate and well-documented (CIWD) HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQB1 and -DPB1 alleles has been compiled from over 8 million individuals using data from 20 unrelated hematopoietic stem cell volunteer donor registries. Individuals are divided into seven geographic/ancestral/ethnic groups and data are summarized for each group and for the total population. P (two-field) and G group assignments are divided into one of four frequency categories: common (≥1 in 10 000), intermediate (≥1 in 100 000), well-documented (≥5 occurrences) or not-CIWD. Overall 26% of alleles in IPD-IMGT/HLA version 3.31.0 at P group resolution fall into the three CIWD categories. The two-field catalog includes 18% (n = 545) common, 17% (n = 513) intermediate, and 65% (n = 1997) well-documented alleles. Full-field allele frequency data are provided but are limited in value by the variations in resolution used by the registries. A recommended CIWD list is based on the most frequent category in the total or any of the seven geographic/ancestral/ethnic groups. Data are also provided so users can compile a catalog specific to the population groups that they serve. Comparisons are made to three previous CWD reports representing more limited population groups. This catalog, CIWD version 3.0.0, is a step closer to the collection of global HLA frequencies and to a clearer view of HLA diversity in the human population as a whole

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Microbial etiology in hospitalized North Indian adults with community-acquired pneumonia

Background: There is a paucity of literature regarding the microbial etiology of community-acquired pneumonia (CAP) in India. The current study was aimed to study the microbial etiology of hospitalized adults with CAP. Methods: The study was conducted in a 700-bedded North Indian hospital. Consecutive adults admitted with CAP over a period of 2 years from 2013 to 2015 were recruited for the study, and apart from clinical evaluation underwent various microbiological studies in the form of blood culture, sputum culture, urinary antigen for pneumococcus and Legionella, serology for Mycoplasma and Chlamydia and real-time reverse transcriptase polymerase chain reaction for influenza viruses. Radiographic studies were performed in all patients and repeated as required. The patients were treated with standard antibiotic/antiviral therapy and outcomes were recorded. Results: A total of 225 patients (median age: 59 years) were enrolled. Streptococcus pneumoniae was the most common organism found (30.5%), followed by Legionella pneumophila (17.5%), influenza viruses (15.4%), Mycoplasma pneumoniae (7.2%), Chlamydia pneumonia (5.5%), Mycobacterium tuberculosis (4.8%), Klebsiella pneumoniae (4.8%), methicillin-resistant Staphylococcus aureus (3.5%), Pseudomonas aeruginosa (3.1%), methicillin-sensitive S. aureus (1.7%), and Acinetobacter sp. (0.8%) with 4% of patients having multiple pathogens etiologies. High Pneumonia Severity Index score correlated with the severity and outcome of the CAP but was not predictive of any definite etiological pathogen. In-hospital mortality was 8%. Conclusion: Streptococcus pneumoniae, Legionella, and influenza constitute the most common etiological agents for north Indian adults with CAP requiring hospitalization. Appropriate antibiotic therapy and preventive strategies such as influenza and pneumococcal vaccination need to be considered in appropriate groups

Two-year mortality in survivors of acute exacerbations of chronic obstructive pulmonary disease: A North Indian study

Objectives: Data about long-term mortality of Indian patients following acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are scant. We set out to study the 2-year mortality in north Indian patients following discharge after AECOPD. Materials and Methods: One hundred and fifty-one (96 male) patients admitted for AECOPD and discharged were followed for 2 years at 3, 6, 12, 18, and 24 months for mortality. Statistical analysis was performed to identify risk factors associated with mortality. Results: Sixty (39.7%) of the 151 recruited died during the 24 months of follow-up, 30 (19.8%) at 3-month, 43 (28.5%) at 6-month, 49 (32.4%) at 1-year, 55 (36.4%) at 18-month, and 60 (39.7%) at 2 years. There was no mortality in Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage I (0 of 6 cases), whereas it was 12.3% (n = 8 of 65 patients) in GOLD Stage II, 41.7% (n = 15 of 36 cases), in GOLD Stage III, and 84.1% (n = 37 of 4 cases), of patients with GOLD Stage IV. Mortality was associated with 6-min walk distance, oxygen saturation, low body mass index, history of congestive heart failure, and St. George Respiratory Questionnaire score. Conclusion: Indian patients discharged after AECOPD have a high 2-year mortality. Measures to reduce the frequency of exacerbations need to be routinely adopted in patients with COPD

Study of irradiation induced changes of electrical and functional characteristics in Ge doped Si diodes

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