Fatal Pneumocystis jirovecii pneumonia in a non-immunocompromised patient with alcohol-related liver cirrhosis.

This report presents the fatal case of a 63-year-old man with a new presentation of liver cirrhosis, presumed concurrent acute alcoholic hepatitis and development of Pneumocystis jirovecii pneumonia. The patient had none of the traditional immunosuppressing risk factors associated with Pneumocystis jirovecii pneumonia such as corticosteroid use, haematological malignancy or HIV infection. In the literature, there are two case reports and a case series of two patients which describe the development of Pneumocystis jirovecii pneumonia in acute alcoholic hepatitis. However, all of these previously described cases include identifiable risk factors - namely corticosteroid use and HIV infection. This case suggests that special consideration should be given to Pneumocystis jirovecii pneumonia as a cause of opportunistic infection in acute alcoholic hepatitis.

Impact of a National Journal Club and Letter Writing Session on Improving Medical Students' Confidence with Critical Appraisal.

BACKGROUND: Critical appraisal is an important skill for clinicians of the future which medical students often have limited opportunities to develop. This study aimed to evaluate whether a national journal club session could improve medical students' confidence with critical appraisal. METHODS: 98 medical students attended a critical appraisal lecture and supervised journal article discussions. Junior doctor mentors supported students to submit discussion points as a letter-to-the-editor. An online cross-sectional survey was administered before and after the conference. RESULTS: 74 students responded, reporting increased confidence with critically appraising research articles (median score 2 vs 4, p<0.01) and increased understanding of why critical appraisal was important to their careers (median score 3 vs 5, p<0.01). DISCUSSION: This is the first study to demonstrate that a single national journal club session can significantly improve UK medical students' confidence with the critical appraisal process. These opportunities are valued by medical students.

Osteoprotegerin and Myocardial Fibrosis in Patients with Aortic Stenosis.

Left ventricular myocardial fibrosis in patients with aortic stenosis (AS) confers worse prognosis. Plasma osteoprotegerin (OPG), a cytokine from the TNF receptor family, correlates with the degree of valve calcification in AS, reflecting the activity of the tissue RANKL/RANK/OPG (receptor activator of nuclear factor κΒ ligand/RANK/osteoprotegerin) axis, and is associated with poorer outcomes in AS. Its association with myocardial fibrosis is unknown. We hypothesised that OPG levels would reflect the extent of myocardial fibrosis in AS. We included 110 consecutive patients with AS who had undergone late-gadolinium contrast enhanced cardiovascular magnetic resonance (LGE-CMR). Patients were characterised according to pattern of fibrosis (no fibrosis, midwall fibrosis, or chronic myocardial infarction fibrosis). Serum OPG was measured with ELISA and compared between groups defined by valve stenosis severity. Some 36 patients had no fibrosis, 38 had midwall fibrosis, and 36 had chronic infarction. Patients with midwall fibrosis did not have higher levels of OPG compared to those without fibrosis (6.78 vs. 5.25 pmol/L, p = 0.12). There was no difference between those with midwall or chronic myocardial infarction fibrosis (6.78 vs. 6.97 pmol/L, p = 0.27). However, OPG levels in patients with chronic myocardial infarction fibrosis were significantly higher than those without fibrosis (p = 0.005).

Correction to: Treatment of Obesity in Young People-a Systematic Review and Meta-analysis.

In the original article, due to a production error, the text for the "Principle Findings" section was omitted as was the heading for the "Strengths and Limitations" section. The original article has been updated to correct these errors.

Treatment of Obesity in Young People-a Systematic Review and Meta-analysis.

Obesity in the young is increasingly prevalent. Early, effective intervention is paramount. Treatment options are lifestyle modifications, pharmacological therapies, endoscopic treatments and bariatric surgery. However, the relative effectiveness of these treatments in young patients remains unclear. We systematically identify and meta-analyse studies evaluating weight loss treatments in young people (< 21 years) with obesity. From 16,372 identified studies, 83 were eligible for meta-analysis. Bariatric surgery resulted in high short/medium-term weight loss (pooled estimate 14.04 kg/m2). Lifestyle and pharmacological therapies impacted weight more moderately (pooled estimate 0.99 and 0.94 kg/m2 respectively). Due to its high efficacy, bariatric surgery should be considered earlier when treating obesity in young people. However, due to the invasiveness and inherent risks of bariatric surgery, all other weight loss routes should be exhausted first.

Chronic urticaria and thyroid autoimmunity: a perplexing association.

Chronic urticaria has long been thought to be associated with autoimmune conditions, in particular autoimmune thyroid disease (AITD). We detail an unusual case of a 49-year-old patient presenting with urticaria distributed on both shins and hands, with no known associated triggers, and subsequently diagnosed with AITD. The urticaria resolved upon treatment of the AITD. We also summarize the currently postulated pathophysiological links between the two diseases. This case highlights that physicians should have a low threshold for investigating autoimmune conditions in cases of chronic urticaria, with particular attention given to AITD.

The Association of Low-Penetrance Variants in DNA Repair Genes with Colorectal Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: Approximately 35% of colorectal cancer (CRC) risk is attributable to heritable factors known hereditary syndromes, accounting for 6%. The remainder may be due to lower penetrance polymorphisms particularly of DNA repair genes. DNA repair pathways, including base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), direct reversal repair (DRR), and double-strand break repair are complex, evolutionarily conserved, and critical in carcinogenesis. Germline mutations in these genes are associated with high-penetrance CRC syndromes such as Lynch syndrome. However, the association of low-penetrance polymorphisms of DNA repair genes with CRC risk remains unclear. METHODS: A systematic literature review of PubMed, Embase, and HuGENet databases was conducted. Pre-specified criteria determined study inclusion/exclusion. Per-allele, pooled odds ratios disclosed the risk attributed to each variant. Heterogeneity was investigated by subgroup analyses for ethnicity and tumor location; funnel plots and Egger's test assessed publication bias. RESULTS: Sixty-one polymorphisms in 26 different DNA repair genes were identified. Meta-analyses for 22 polymorphisms in 17 genes revealed that six polymorphisms were significantly associated with CRC risk within BER (APE1, PARP1), NER (ERCC5, XPC), double-strand break (RAD18), and DRR (MGMT), but none within MMR. Subgroup analyses revealed significant association of OGG1 rs1052133 with rectal cancer risk. Egger's test revealed no publication bias. CONCLUSIONS: Low-penetrance polymorphisms in DNA repair genes alter susceptibility to CRC. Future studies should therefore analyze whole-genome polymorphisms and any synergistic effects on CRC risk.Translational impact:This knowledge may enhance CRC risk assessment and facilitate a more personalized approach to cancer prevention.

Lipoprotein(a) in patients with aortic stenosis: Insights from cardiovascular magnetic resonance.

BACKGROUND: Aortic stenosis is the most common age-related valvular pathology. Patients with aortic stenosis and myocardial fibrosis have worse outcome but the underlying mechanism is unclear. Lipoprotein(a) is associated with adverse cardiovascular risk and is elevated in patients with aortic stenosis. Although mechanistic pathways could link Lipoprotein(a) with myocardial fibrosis, whether the two are related has not been previously explored. In this study, we investigated whether elevated Lipoprotein(a) was associated with the presence of myocardial replacement fibrosis. METHODS: A total of 110 patients with mild, moderate and severe aortic stenosis were assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance to identify fibrosis. Mann Whitney U tests were used to assess for evidence of an association between Lp(a) and the presence or absence of myocardial fibrosis and aortic stenosis severity and compared to controls. Univariable and multivariable linear regression analysis were undertaken to identify possible predictors of Lp(a). RESULTS: Thirty-six patients (32.7%) had no LGE enhancement, 38 (34.6%) had midwall enhancement suggestive of midwall fibrosis and 36 (32.7%) patients had subendocardial myocardial fibrosis, typical of infarction. The aortic stenosis patients had higher Lp(a) values than controls, however, there was no significant difference between the Lp(a) level in mild, moderate or severe aortic stenosis. No association was observed between midwall or infarction pattern fibrosis and Lipoprotein(a), in the mild/moderate stenosis (p = 0.91) or severe stenosis patients (p = 0.42). CONCLUSION: There is no evidence to suggest that higher Lipoprotein(a) leads to increased myocardial midwall or infarction pattern fibrosis in patients with aortic stenosis.

The role of myocardial fibrosis in determining the success rate of ablation for the treatment of atrial fibrillation.

Atrial fibrillation is the most common sustained cardiac arrhythmia and with an aging population its prevalence will increase. In addition to appropriate anticoagulation to reduce the thromboembolic risk, there has been an increasing need for a personalized approach in identifying which patients are likely to benefit more from atrial fibrillation ablation procedures. This review will discuss the role of myocardial fibrosis in patients with atrial fibrillation, its mechanistic role, association with biomarkers and how this could potentially be of use in the development of a risk score identifying the success of maintaining sinus rhythm following an electrophysiological ablation.

Atrial Fibrillation in the Young: A Neurologist's Nightmare.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia seen in clinical practice with prevalence in excess of 33 million worldwide. Although often asymptomatic and until recently considered a "benign" arrhythmia, it is now appreciated that thromboembolism resulting from AF results in significant morbidity and mortality predominantly due to stroke. Although an arrhythmia more commonly affecting the elderly, AF can also occur in the young. This review focuses on the impact of AF in the younger population and discusses the dilemmas of managing younger patients with AF.