Identifying modifier genes for hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) severity greatly varies among patients even with the same HCM gene mutations. This variation is largely regulated by modifier gene(s), which, however, remain largely unknown. The current study is aimed to identify modifier genes using BXD strains, a large murine genetic reference population (GRP) derived from crosses between C57BL/6 J (B6) and D2 DBA/2 J (D2) mice. D2 mice natualy carrythe genetic basis and phenotypes of HCM. METHODS: Myocardial hypertrophy, the major phenotype of HCM, was determined by cardiomyocyte size on cardiac sections in 30 BXD strains, and their parental B6 and D2 strains and morphometric analysis was performed. Quantitative Trait Locus (QTL) mapping for cardiomyocyte sizes was conducted with WebQTL in GeneNetwork. Correlation of cardiomyocyte size and cardiac gene expression in BXDs accessed from GeneNetwork were evaluated. QTL candidate genes associated with cardiomyocyte sizes were prioritized based on the score system. RESULTS: Cardiomyocyte size varied significantly among BXD strains. Interval mapping on cardiomyocyte size data showed a significant QTL on chromosome (Chr) 2 at 66- 73.5 Mb and a suggestive QTL on Chr 5 at 20.9-39.7 Mb. Further score system revealed a high QTL score for Xirp2 in Chr 2. Xirp2 encodes xin actin-binding repeat containing 2, which is highly expressed in cardiac tissue and associate with cardiomyopathy and heart failure. In Chr5 QTL, Nos3, encoding nitric oxide synthase 3, received the highest score, which is significantly correlated with cardiomyocyte size. CONCLUSION: These results indicate that Xirp2 and Nos3 serve as novel candidate modifier genes for myocardial hypertrophy in HCM. These candidate genes will be validated in our future studies.

Critical appraisal of the impact of surgical repair of type II-IV paraoesophageal hernia (POH) on pulmonary improvement: A systematic review and meta-analysis.

BACKGROUND: Paraoesophageal hernia (POH) comprising type II-IV hiatal hernia often presents with pulmonary symptoms such as shortness of breath. However, impact of surgical repair on improvement in pulmonary symptoms is unclear. OBJECTIVE: This systematic review and meta-analysis aimed at characterising impact of POH repair on patient reported improvement in pulmonary symptoms. METHODS: This systematic review identified studies reported pulmonary symptoms in patients with undergoing surgical repair for Type II-IV POH from 1st January 2001 to 1st December 2018. Primary outcome was improvement in pulmonary symptoms. Secondary outcomes were improvement in other patient-reported outcomes such as heartburn, regurgitation, chest pain, and dysphagia and intraoperative and postoperative outcomes. RESULTS: This systematic review identified 27 studies (n = 4428 patients) reporting assessment of pulmonary symptoms. However, only 21 studies (n = 2902 patients) reported preoperative and postoperative pulmonary symptoms and hence these were included in the final meta-analysis. There was significant improvement in pulmonary symptoms following POH repair (OR: 8.40, CI95%: 4.91-14.35, p < 0.001), with improvement in all types of POH. Rates of overall and major complications were 16% and 5%, respectively. Rates of conversion, 30-day mortality, reoperation and recurrence were 2%, 1% 4% and 12% respectively. CONCLUSION: This review demonstrates that POH repair is associated with improvement in pulmonary symptoms with acceptable low laparoscopic conversion rates, morbidity, mortality and recurrence rates.

Critical appraisal of gastric conduit ischaemic conditioning (GIC) prior to oesophagectomy: A systematic review and meta-analysis.

INTRODUCTION: Anastomotic leaks remain a major complication following oesophagectomy, accounting for high morbidity and mortality. Recently, gastric ischaemic conditioning (GIC) has been proposed to improve anastomotic integrity through neovascularisation of the gastric conduit. This systematic review and meta-analysis aim to determine the impact of GIC on postoperative outcomes following oesophagectomy. METHODS: A systematic literature search was performed to identify studies reporting GIC for any indication of oesophageal resection up to April 25, 2019. The primary outcome was anastomotic leak. Secondary outcomes were conduit necrosis, anastomotic strictures, overall and major complications or in-hospital mortality. Meta-analyses were conducted using random-effects modelling. RESULTS: Nineteen studies reported on GIC, of which 13 were comparative studies. GIC was performed through ligation in 13 studies and embolisation in six studies. GIC did not appear to reduce anastomotic leakages (OR 0.80, CI95: 0.51-1.24, p = 0.3), anastomotic strictures (OR 0.75, CI95: 0.35-1.60, p = 0.5), overall complications (OR 1.02, CI95: 0.48-2.16, p = 0.9), major complications (OR 1.06, CI95: 0.53-2.11, p = 0.9), or in-hospital mortality (OR 0.70, CI95: 0.32-1.53, p = 0.4). However, GIC was associated with reduced rates of conduit necrosis (OR 0.30, CI95: 0.11-0.77, p = 0.013). CONCLUSION: GIC does not appear to reduce overall rates of anastomotic leakage after oesophagectomy but seems to reduce severity of leakages. More in depth studies are recommended.