Methylprednisolone in severe COVID-19 with acute respiratory distress syndrome - less is more?

INTRODUCTION: Corticosteroids, particularly methylprednisolone, are part of the treatment for severe COVID-19 with acute respiratory distress syndrome (ARDS). In this study, we aimed to compare the mortalities of patients treated with higher versus lower doses of methylprednisolone. Secondary outcomes included oxygenation, need for mechanical ventilation, length of stay in intensive care unit (ICU), secondary infection, improvement of PaO2/FiO2 (PF) ratio, and inflammatory response as expressed by C-reactive protein (CRP). MATERIALS AND METHODS: A retrospective cohort study conducted at Sarawak General Hospital from 1st June to 30th September 2021. Patients who received intravenous methylprednisolone for severe COVID-19 in the ICU were identified and divided into two groups: higher dose (cumulative dose more than 10 mg per kg) and lower dose (cumulative dose less than 10 mg per kg). RESULTS: Out of a total of 165 patients, 40 (24.2%) patients received higher dose methylprednisolone. There was no significant difference in socio-demographic characteristics (age, gender, body mass index), COVID-19 vaccination status, laboratory parameters (lymphocyte count, CRP, lactate dehydrogenase, D-dimer), or usage of immunomodulator therapy between the groups. Overall mortality was 23.6%. Mortality in the higher dose group was twice as high compared to lower dose group (37.5% versus 19.2%) (OR 3.79, 95% CI 1.24-11.59, p<0.05). In addition, the higher dose cohort developed more secondary infections (87.5%) and had longer stays in ICU (median 11 days, IQR 8- 15). No significant difference was found between both cohorts in terms of CRP reduction, improvement of PF ratio, or the need for mechanical ventilation post methylprednisolone. CONCLUSION: In this study, the use of higher dose methylprednisolone in COVID-19 with ARDS was not associated with better clinical outcomes. A lower dose of methylprednisolone might be sufficient in treating severe COVID-19 with ARDS.

Epidemiology and outcomes of primary sclerosing cholangitis: an Australian multicentre retrospective cohort study.

BACKGROUND AND AIMS: Little is known regarding the epidemiology and outcomes of patients with primary sclerosing cholangitis (PSC) in Australia. We, therefore, evaluated the epidemiology and clinical outcomes of PSC in a large cohort of Australian patients and compared these to the general population. METHODS: We conducted a multicentre, retrospective cohort study of PSC patients at nine tertiary liver centers across three Australian states, including two liver transplant centers. RESULTS: A total of 413 PSC patients with 3,285 person-years of follow-up were included. Three hundred and seventy-one (90%) patients had large duct PSC and 294 (71%) had associated inflammatory bowel disease. A total of 168 (41%) patients developed cirrhosis (including 34 at the time of PSC diagnosis) after a median of 15.8 (95% CI 12.4, NA) years. The composite endpoint of death or liver transplantation occurred in 49 (12%) and 78 (19%) patients, respectively, with a median transplant-free survival of 13.4 (95% CI 12.2-15) years. Compared to the general population, PSC accounted for a 240-fold increased risk of development of cholangiocarcinoma (CCA) and CCA-related death. CCA risk was increased with older age of PSC diagnosis, presence of dominant stricture and colectomy. Compared to same-aged counterparts in the general population, PSC patients who were diagnosed at an older age or with longer disease duration had reduced relative survival. CONCLUSION: In this large retrospective cohort study of PSC patients in Australia, increased age and time from diagnosis was associated with increased mortality and morbidity particularly from CCA and development of cirrhosis, necessitating need for liver transplant.

Tree-in-Bud Opacities: Not only tuberculosis.

We report a clinical case of mentally challenged young gentleman who was repeatedly hospitalized for respiratory symptoms. Contrast-enhanced CT (computed tomography) thorax revealed tree-in-bud (TIB) opacities. Provisional diagnosis of pulmonary tuberculosis was made and was referred to the respiratory team. However, after listening to patient's voice and reviewing the images on CT thorax, the diagnosis was confirmed as aspiration bronchiolitis.

Relationship between myosin heavy chain isoform expression and muscling in several diverse pig breeds.

The objective of this study was to examine the relationship of the relative abundance of transcripts of myosin heavy chain (MyHC) isoforms and muscling in several diverse pig breeds. The animals used were from 3 pure breeds (Pietrain, Duroc, and Mongcai) and 2 crosses [Duroc x Pietrain (DUPI) and Duroc x Berlin Miniature pigs (DUMI)]. Real-time PCR quantification of MyHC isoforms I, IIa, IIx, and IIb showed that the relative expression of MyHC IIb was greater in pigs with large LM areas in both DUPI (69.6 vs. 53.0%) and DUMI (60.5 vs. 47.5%). In DUPI, similar transcript levels of MyHC I were found in both large and small LM (14.7 and 15.2%), whereas in DUMI animals, these values were 18.4 and 33.5% (P < 0.05). The groups of animals with large and small LM area in the DUPI also tended to differ in MyHC IIa and IIx transcripts. The comparison among different breeds confirmed the trend of high MyHC IIb transcript abundance together with high muscularity. In Pietrain, Duroc, DUPI, and DUMI, MyHC IIb accounted for more than half of the MyHC transcripts (65.4, 59.7, 54.0, and 54.0%). Mongcai showed low MyHC IIb (11.4%) but high type I, IIa, and IIx relative RNA levels (24.1, 28.5, and 35.9%). Frequencies of fibers, determined by muscle fiber staining with ATPase, and relative abundance of MyHC isoforms, determined by quantitative reverse transcription-PCR, of corresponding pairs of type I, IIa, and IIx/ IIb were correlated (r = 0.71, 0.67, and 0.52, respectively). The study demonstrates that MyHC IIb fibers are the most prominent in pigs having large LM area and implies that MyHC IIb is the determining fiber contributing to the differentiation of large and small loin eye muscle area in the pig.

Structural and functional genomics to elucidate the genetic background of microstructural and biophysical muscle properties in the pig.

Linkage analyses enable identifying genomic regions that exhibit quantitative trait loci (QTL) without prior hypothesis on the physiology of a trait. Function-oriented expression analyses are a complementary approach to derive hypothesis on the genetic background of phenotypic variation. Muscle fibre types and size affect body composition and meat quality traits. The number and proportion of muscle fibres are to a large extent determined during the prenatal development. Consequently, QTL for muscle fibre, meat quality and carcass traits were detected in a porcine experimental population based on Duroc and Berlin Miniature Pig. Regions with either significant QTL for muscle fibre traits or significant QTL for meat quality and muscularity or both were detected on SSC1, 2, 3, 4, 5, 13, 14, 15 and 16. Here, effects on the complex traits of muscularity and meat quality might be the result of genetic variation primarily affecting fibre type distribution traits. To complement the QTL study expression profiling of prenatal muscle tissue of Duroc and Pietrain was conducted that revealed a list of functional candidate genes for meat quality and carcass traits of various physiological networks. Assignments of these genes to QTL regions highlight them as positional functional candidates. Exemplarily, five genes were analysed further and shown to be associated with meat quality and carcass traits. Further, the relative MYH isotype transcript abundance was found to be associated with muscularity. Relative MYH isotype transcript abundance is proposed as a new phenotype to unravel the genetic background of variation in traits related to muscle and meat properties.