SHORT COMMUNICATION: Reduction of Spirometric Lung Function Tests in Habitually Smoking Healthy Young Adults: Its Correlation with Pack Years

Background: Adolescent smoking and the subsequent health problems are a major concern today. However there are very few studies done on spirometric lung functions and its relation with pack years in young adult habitual smokers who are apparently healthy. Aims and Objectives: The present study is undertaken to assess the change in lung functions in apparently healthy young adult habitual smokers compared to their age matched controls. Materials and Methods: A random sample of apparently healthy young adult habitual smokers (n=40) and nonsmokers (n=40) between age group17-35 years with history suggesting of pack years of 2-10 years were selected from students & employees of B.L.D.E.Us Sri B.M. Patil Medical College,Hospital & Research Centre Bijapur (Karnataka), India. Spirometric lung functions recorded were forced expiratory volume in one second (FEV1), FEV1%, Peak expiratory flow rate (PEFR) and Maximal expiratory pressure (MEP). Results: The results suggested that inapparently healthy habitual smokers there was significant decrease in FEV1 (L) (-13.34%, p<0.001), FEV1 % (-10.76%, p<0.001), PEFR (-45.26%, p<0.0001) and MEP (-35.51%, p<0.0001) compared to nonsmokers and decrease in FEV1 was negatively correlated withpack years in smokers (r2=0.063, p=0.001). Reduced lung functions and negative correlation to pack years may be attributed todecreased airway diameter & reflex broncho- constriction in response to inhaled smoke particles. Conclusions: In conclusion young adulthabitual smokers who were apparently healthy are more prone for respiratory dysfunction than their nonsmoker counterparts. FEV1 reduction in relation to pack years acts as an important determinant for detecting lung dysfunction in the early stage of the disease. As the risk of having smoking related diseases depends mainly on number of pack years, it is suggested that quitting smoking earliest helps to get greatest health benefits in apparently healthy young adult habitual smokers

Obesity is the most common risk factor for chronic liver disease: Results from risk stratification pathway using transient elastography

IntroductionObesity has been associated with liver fibrosis yet guidelines do not emphasise it as an independent risk factor in which to have a high index of suspicion of advanced disease. We aimed to elucidate the effect of a raised body mass index on the risk of liver disease using data from a community risk stratification pathway. MethodsWe prospectively recruited patients from a primary care practice with hazardous alcohol use and/or type 2 diabetes and/or obesity. Subjects were invited for a transient elastography reading. A threshold of ≥8.0kPa defined an elevated reading consistent with clinically significant liver disease. ResultsFive hundred and seventy six patients participated in the pathway of which, 533 patients had a reliable reading and 66 (12.4%) had an elevated reading. Thirty one percent of patients with an elevated reading had obesity as their only risk factor. The proportion of patients with an elevated reading was similar among those with obesity (8.9%) to patients with more recognised solitary risk factors (Type 2 diabetes 10.8%; Hazardous alcohol use 4.8%). Obesity in combination with other risk factors further increased the proportion of patients with an elevated reading. In multivariate logistic regression, increasing BMI and type 2 diabetes were significantly associated with an elevated reading. ConclusionObesity as a single or additive risk factor for chronic liver disease is significant. Future case finding strategies using a risk factor approach should incorporate obesity within proposed algorithms

Classifying the unclassifiable – A Delphi study to reach consensus on the fibrotic nature of diseases

Background Traditionally, clinical research has focused on individual fibrotic diseases or fibrosis in a particular organ. However, it is possible for people to have multiple fibrotic diseases. While multi-organ fibrosis may suggest shared pathogenic mechanisms, yet there is no consensus on what constitutes a fibrotic disease and therefore fibrotic multimorbidity. Aim A Delphi study was performed to reach consensus on which diseases may be described as fibrotic. Methods Participants were asked to rate a list of diseases, sub-grouped according to eight body regions, as ‘fibrotic manifestation always present’, ‘can develop fibrotic manifestations’, ‘associated with fibrotic manifestations’ or ‘not fibrotic nor associated’. Classifications of ‘fibrotic manifestation always present’ and ‘can develop fibrotic manifestations’ were merged and termed ‘fibrotic’. Clinical consensus was defined according to the interquartile range, having met a minimum number of responses. Clinical agreement was used for classification where diseases did not meet the minimum number of responses (required for consensus measure), were only classified if there was 100% consensus on disease classification. Results After consulting experts, searching the literature and coding dictionaries, a total of 323 non-overlapping diseases which might be considered fibrotic were identified; 92 clinical specialists responded to the first round of the survey. Over three survey rounds, 240 diseases were categorized as fibrotic via clinical consensus and 25 additional diseases through clinical agreement. Conclusion Using a robust methodology, an extensive list of diseases was classified. The findings lay the foundations for studies estimating the burden of fibrotic multimorbidity, as well as investigating shared mechanisms and therapies

Validation of the AASLD recommendations for Classification of Oesophageal Varices in Clinical Practice

Background & Aims The American Association for the Study of Liver Diseases recommends the use of a 2‐grade classification system (small and large) to describe the size of oesophageal varices (OV). Data on observer agreement (OA) on this system are currently lacking. We aimed to evaluate this classification and compare it to the widely used 3‐grade classification (grade 1 ‘small’, grade 2 ‘medium’, grade 3 ‘large’) among operators of variable experience. Methods High‐definition video recordings of 100 patients with cirrhosis were prospectively collected using standardised criteria. Nine observers of variable experience performed independent evaluations of the videos in random order. OV were scored using both systems. All assessments were repeated a year later by the same observers to assess intra‐observer agreement. Results Interobserver agreement (all observers) using the 2‐grade and the 3‐grade system was k = 0.71 (95% CI: 0.64‐0.78) and k = 0.73 (95% CI: 0.66‐0.79) respectively. When using the 2‐grade system, intra‐observer agreement between hepatologists (n = 3), luminal gastroenterologists (n = 3) and trainee gastroenterologists (n = 3) was k = 0.89 (95% CI: 0.86‐0.91), k = 0.72 (95% CI: 0.67‐0.77), and k = 0.74 (95% CI: 0.67‐0.8) respectively. With the 3‐grade system; intra‐observer agreement between the same three subgroups were k = 0.9 (95% CI: 0.87‐0.92), k = 0.73 (95% CI: 0.68‐0.78), k = 0.77 (95% CI: 0.71‐0.82) respectively. Conclusions There was no difference in OA between the 2‐grade and 3‐grade classification systems. Hepatologists had significantly higher levels of consistency in grading OV. This may have implications to create alternative training models for residents and fellows in the recognition and grading of OV

Development and mechanical characterization of cenosphere-reinforced CFRP and natural rubber core sandwich composite

Driven by the growing concern for environmental sustainability, there is an increasing need to explore innovative approaches for repurposing industrial waste materials. This study focuses on investigating the potential uses and challenges associated with cenosphere, a waste product derived from coal combustion in thermal power plants. Typically regarded as waste, cenosphere offers an opportunity to contribute to sustainability efforts. The objective of this research is to evaluate the influence of cenosphere, a ceramic-rich industrial waste, on the mechanical properties of woven CFRP-Rubber-CFRP (Carbon fibre-reinforced polymers) sandwich composites. The composite specimens were fabricated using the conventional hand lay-up technique, incorporating different weight percentages (5, 10, 15, and 20 wt.%) of cenosphere as a particulate filler. Tensile, flexural, and impact testing were conducted according to ASTM standards to assess the impact of the filler content on the mechanical properties. The results demonstrate that the inclusion of approximately 15% by weight of discarded cenosphere significantly enhances the tensile strength, flexural strength, interlaminar shear strength (ILSS), and impact strength of the sandwich composites, yielding improvements of approximately 1.6, 1.56, 2.06, and 1.85 times, respectively, compared to unfilled composites. Microscopic analysis of the composites reveals a well-dispersed cenosphere distribution within the matrix, contributing to the notable enhancement in overall strength characteristics

In severe alcoholic hepatitis, serum keratin-18 fragments are diagnostic, prognostic, and theragnostic biomarkers.

INTRODUCTION: Up to 40% of patients with severe alcoholic hepatitis (AH) die within 6 months of presentation, making prompt diagnosis and appropriate treatment essential. We determined the associations between serum keratin-18 (K18) and histological features, prognosis, and differential response to prednisolone in patients with severe AH. METHODS: Total (K18-M65) and caspase-cleaved K18 (K18-M30) were quantified in pretreatment sera from 824 patients enrolled in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial (87 with suitable histological samples) and disease controls. RESULTS: K18 fragments were markedly elevated in severe AH and strongly predicted steatohepatitis (alcoholic steatohepatitis) on biopsy (area under receiver operating characteristics: 0.787 and 0.807). Application of published thresholds to predict alcoholic steatohepatitis would have rendered biopsy unnecessary in 84% of all AH cases. K18-M30 and M65 were associated with 90-day mortality, independent of age and Model for End-stage Liver Disease score in untreated patients. The association for K18-M65 was independent of both age and Model for End-stage Liver Disease in prednisolone-treated patients. Modelling of the effect of prednisolone on 90-day mortality as a function of pretreatment serum K18 levels indicated benefit in those with high serum levels of K18-M30. At low pretreatment serum K18 levels, prednisolone was potentially harmful. A threshold of K18-M30 5 kIU/L predicted therapeutic benefit from prednisolone above this level (odds ratio: 0.433, 95% confidence interval: 0.19-0.95, P = 0.0398), but not below (odds ratio: 1.271, 95% confidence interval: 0.88-1.84, P = 0.199). Restricting prednisolone usage to the former group would have reduced exposure by 87%. DISCUSSION: In a large cohort of patients with severe AH, serum K18 strongly correlated with histological severity, independently associated with 90-day mortality, and predicted response to prednisolone therapy. Quantification of serum K18 levels could assist in clinical decision-making

Multicenter experience from the UK and Ireland of use of lumen-apposing metal stent for transluminal drainage of pancreatic fluid collections

Background and study aims: Pancreatic fluid collection (PFC) is a common complication of pancreatitis for which endoscopic ultrasound-guided drainage is first-line treatment. A new single-device, lumen-apposing, covered self-expanding metal stent (LAMS) has been licensed for PFC drainage. We therefore present our multicenter experience with the LAMS for PFC drainage in a multicenter prospective case series to assess success and complication rates. Patients and methods: All adult patients from 11 tertiary centers who had LAMS placement for PFC from July 2015 to July 2016 were included. Data including indications, technical success, clinical success, collection resolution, stent removal, early and late adverse events (AEs), mortality and recurrence at 6 months were collected. Results: 116 patients, median age 52.5 years (range 16 – 80) and 67 % male, were treated with a single LAMS in each case. The indication was walled off necrosis (WON) in 70 and pseudocyst in 46. Median size of the PFC was 11 cm (5 – 21 cm) and the estimated median necrotic volume in WON was 30 % (5 % – 90 %). Stent insertion was technically successful in 115 (99.1 %) and clinically successful in 109 (94 %). Early serious AEs (SAEs): n = 7 sepsis, n = 1 stent blockage with food, n = 1 stent migration requiring laparotomy, n = 1 stent dislodgement and n = 1 bleeding requiring emboliZation. Late AEs: n = 1 buried stent and n = 1 esophageal fistula. Non-procedure-related deaths: n = 3 (2.5 %). Conclusion: This multicenter case series demonstrates that use of the new LAMS is feasible, effective and relatively safe in draining PFC with a technical success rate of 99 % and cumulative SAE rate of 11.2 %

Longitudinal assessment of symptoms and risk of SARS-CoV-2 infection in healthcare workers across 5 hospitals to understand ethnic differences in infection risk.

BACKGROUND: Healthcare workers (HCWs) have increased rates of SARS-CoV-2 infection compared with the general population. We aimed to understand ethnic differences in SARS-CoV-2 seropositivity among hospital healthcare workers depending on their hospital role, socioeconomic status, Covid-19 symptoms and basic demographics. METHODS: A prospective longitudinal observational cohort study. 1364 HCWs at five UK hospitals were studied with up to 16 weeks of symptom questionnaires and antibody testing (to both nucleocapsid and spike protein) during the first UK wave in five NHS hospitals between March 20 and July 10 2020. The main outcome measures were SARS-CoV-2 infection (seropositivity at any time-point) and symptoms. Registration number: NCT04318314. FINDINGS: 272 of 1364 HCWs (mean age 40.7 years, 72% female, 74% White, ≥6 samples per participant) seroconverted, reporting predominantly mild or no symptoms. Seropositivity was lower in Intensive Therapy Unit (ITU) workers (OR=0.44 95%CI 0.24, 0.77; p=0.0035). Seropositivity was higher in Black (compared to White) participants, independent of age, sex, role and index of multiple deprivation (OR=2.61 95%CI 1.47-4.62 p=0.0009). No association was seen between White HCWs and other minority ethnic groups. INTERPRETATION: In the UK first wave, Black ethnicity (but not other ethnicities) more than doubled HCWs likelihood of seropositivity, independent of age, sex, measured socio-economic factors and hospital role

Short-term changes observed in multi-parametric liver MRI following therapy with direct acting antivirals in chronic hepatitis C virus patients

Methods: We applied multiparametric MRI to assess changes in liver composition, perfusion and blood flow in 17 patients before DAA therapy and after treatment completion (within 12 weeks of last DAA tablet swallowed).Results: We observed changes in hepatic composition indicated by a reduction in both liver longitudinal relaxation time (T1, 35±4 ms), transverse relaxation time (T2, 2.5±0.8 ms; T2* 3.0±0.7 ms) and liver perfusion (28.1±19.7ml/100g/min) which we suggest are linked to reduced pro-inflammatory milieu, including interstitial oedema, within the liver. No changes were observed in liver or spleen blood flow, splenic perfusion, or SMA blood flow.Conclusion: For the first time, our study has shown that treatment of HCV with DAAs in patients with cirrhosis leads to an acute reduction in liver T1, T2, T2* and an increase in liver perfusion measured using MR parameters. The ability of MRI to characterise changes in the angio-architecture of patients with cirrhosis after intervention in the short term will enhance our understanding of the natural history of regression of liver disease and potentially influence clinical decision algorithms