Genome-Wide Meta-Analysis Identifies Three Novel Susceptibility Loci and Reveals Ethnic Heterogeneity of Genetic Susceptibility for IgA Nephropathy

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咪达唑仑术前喷鼻对儿童在七氟烷诱导期间癫痫样脑电图的影响

目的 评估咪达唑仑术前喷鼻对儿童在七氟烷诱导麻醉期间癫痫样放电的影响。方法 将择期行全身麻醉下口腔颌面外科手术的86例患者（ASA分级Ⅰ~Ⅱ级,年龄0.5~6岁）,随机分为咪达唑仑组和生理盐水组2组。患儿在等候区予以术前药物喷鼻,入室后以相同步骤行8%七氟烷面罩诱导,持续监测麻醉诱导期间脑电图改变。采用SPSS 25.0软件包对数据进行统计学分析。结果 咪达唑仑组23例（53%,包括DSP30%、PSR37%、PED9%）、生理盐水组29例（67%,包括DSP37%、PSR35%、PED19%）患儿发生癫痫样脑电图改变,2组癫痫样脑电图发生率无统计学差异（P=0.186）。咪达唑仑组意识丧失时间早于生理盐水组,但差异无显著性[（41.6±11.0）s ∶（44.1±16.1）s,P=0.409]。结论 0.4 mg/kg咪达唑仑术前喷鼻并不能减少儿童在七氟烷诱导期间的癫痫样脑电图发生。     

An Adrenal Incidentaloma Diagnosed as Dopamine-Secreting Pheochromocytoma: A Case Report

BackgroundDopamine-secreting pheochromocytomas are exceedingly rare.Case presentationA 28-year-old woman, who was admitted due to 4 hours of acute-onset abdominal pain, detected an adrenal mass incidentally. She was almost asymptomatic without a known family history. Laboratory assessments showed significant increases in dopamine levels of serum and 24-h urinary. By using preoperative a-adrenergic receptor blockers, she developed orthostatic hypotension and palpitations. When she underwent laparoscopic left adrenalectomy, she experienced rapid cyclic fluctuations in systolic blood pressure from 90 mmHg to 200 mmHg. Postoperatively, she exhibited prolonged hypotension, requiring vasopressor therapy and fluid replacement. According to histopathological diagnosis, it was a pheochromocytoma. Dopamine levels in 24-h urine and serum decreased to normal after operation. Analysis of specific gene SDHB, SDHD, RET, VHL and NF1 detected no pathogenic mutations.ConclusionPatients with dopamine-secreting pheochromocytomas are mostly asymptomatic, leading to a significant delay in diagnosis. There is a large possibility for dopamine-secreting pheochromocytomas to show a malignant tendency than the adrenergic and noradrenergic phenotypes. The a-adrenergic receptor blocker is not indicated for preoperative medical treatment because it can cause hypotension and cardiovascular failure. Calcium channel blockers or metyrosine may be better alternatives. All patients with pheochromocytomas should receive targeted genetic testing based on specific clinical features. SDHB, SDHD, RET, VHL and NF1 mutations are suggested for genetic testing of adrenal dopamine-secreting pheochromocytomas.     

A phase 1/2 trial of ibrutinib in combination with pembrolizumab in patients with mismatch repair proficient metastatic colorectal cancer

Background MMR proficient (pMMR) colorectal cancer (CRC) is usually unresponsive to immunotherapy. Recent data suggest that ibrutinib may enhance the anti-tumour activity of anti-PD-1 immunotherapy. In this study, we evaluated the safety and efficacy of ibrutinib plus pembrolizumab in refractory metastatic CRC.Methods This was a phase 1/2 study in patients with refractory metastatic pMMR CRC. The primary endpoints for phases 1 and 2 were maximum tolerated dose (MTD) and disease control rate, respectively. The secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS).Results A total of 40 patients were enrolled. No dose-limiting toxicity was observed, and MTD was not identified. The highest tested dose of ibrutinib, 560 mg once daily, was combined with a fixed dose of pembrolizumab 200 mg every 3 weeks for the phase 2 portion. The most common grade 3/4 treatment-related adverse events were anaemia (21%), fatigue (8%) and elevated alkaline phosphatase (8%). Among 31 evaluable patients, 8 (26%) achieved stable disease, and no objective response was observed. The median PFS and OS were 1.4 and 6.6 months, respectively.Conclusion Ibrutinib 560 mg daily plus pembrolizumab 200 mg every 3 weeks appears to be well tolerated with limited anti-cancer activity in metastatic CRC.ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT03332498","term_id":"NCT03332498"}}NCT03332498.Subject terms: Cancer immunotherapy, Colorectal cancer