Genotype-phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency

Pyruvate kinase (PK) deficiency is a rare recessive congenital hemolytic anemia caused by mutations in the PKLR gene. This study reports the molecular features of 257 patients enrolled in the PKD Natural History Study. Of the 127 different pathogenic variants detected, 84 were missense and 43 non-missense, including 20 stop-gain, 11 affecting splicing, five large deletions, four in-frame indels, and three promoter variants. Within the 177 unrelated patients, 35 were homozygous and 142 compound heterozygous (77 for two missense, 48 for one missense and one non-missense, and 17 for two non-missense variants); the two most frequent mutations were p.R510Q in 23% and p.R486W in 9% of mutated alleles. Fifty-five (21%) patients were found to have at least one previously unreported variant with 45 newly described mutations. Patients with two non-missense mutations had lower hemoglobin levels, higher numbers of lifetime transfusions, and higher rates of complications including iron overload, extramedullary hematopoiesis, and pulmonary hypertension. Rare severe complications, including lower extremity ulcerations and hepatic failure, were seen more frequently in patients with non-missense mutations or with missense mutations characterized by severe protein instability. The PKLR genotype did not correlate with the frequency of complications in utero or in the newborn period. With ICCs ranging from 0.4 to 0.61, about the same degree of clinical similarity exists within siblings as it does between siblings, in terms of hemoglobin, total bilirubin, splenectomy status, and cholecystectomy status. Pregnancy outcomes were similar across genotypes in PK deficient women. This report confirms the wide genetic heterogeneity of PK deficiency.     

胼周动脉动脉瘤42例治疗分析

目的 探讨胼周动脉动脉瘤（PAA）治疗方法及临床疗效。方法 回顾性分析2012年6月至2020年3月收治的42例PAA的临床资料。25例采用夹闭术治疗，17例行血管内栓塞治疗。结果 所有动脉瘤均成功完成夹闭或栓塞，夹闭术后并发症发生率为（48.0%，12/25），栓塞术后并发症发生率（17.6%，3/17）。42例术后临床随访3~12个月，中位数6个月；夹闭术治疗25例末次随访改良Rankin量表（mRS）评分0~2分17例，3~6分8例；预后良好率为68.0%（17/25）；栓塞治疗的17例末次随访mRS评分0~2分14例，3~6分3例；预后良好率为82.4%（14/17）。42例术后影像随访4~21个月，中位数9个月；夹闭术后复发率为12.0%（3/25），栓塞术后复发率为5.9%（1/17）。结论 夹闭术与血管内栓塞是治疗破裂PAA的有效方法，临床上需结合病人具体情况选择个体化的治疗方式以提高治疗效果。     

The role of cardiac CT in women

Due to the discrepancy between higher symptom burden and lower disease prevalence, the diagnosis of coronary artery disease (CAD) in women is challenging. Cardiac CT can be particularly useful in CAD diagnosis and risk stratification in women. In this review, we explore cardiac CT in women with and without symptoms and for adjudication of functional tests. Novel CT technologies such as fractional flow reserve and stress perfusion imaging and their potential for usefulness in women are also examined.