Heterozygous Mutations in Natriuretic Peptide Receptor‐B (NPR2) Gene as a Cause of Short Stature

Based on the observation of reduced stature in relatives of patients with acromesomelic dysplasia, Maroteaux type (AMDM), caused by homozygous or compound heterozygous mutations in natriuretic peptide receptor‐B gene (NPR2), it has been suggested that heterozygous mutations in this gene could be responsible for the growth impairment observed in some cases of idiopathic short stature (ISS). We enrolled 192 unrelated patients with short stature and 192 controls of normal height and identified seven heterozygous NPR2 missense or splice site mutations all in the short stature patients, including one de novo splice site variant. Three of the six inherited variants segregated with short stature in the family. Nine additional rare nonsynonymous NPR2 variants were found in three additional cohorts. Functional studies identified eight loss‐of‐function mutations in short individuals and one gain‐of‐function mutation in tall individuals. With these data, we were able to rigorously verify that NPR2 functional haploinsufficiency contributes to short stature. We estimate a prevalence of NPR2 haploinsufficiency of between 0 and 1/26 in people with ISS. We suggest that NPR2 gain of function may be a more common cause of tall stature than previously recognized.     

Developing Item Response Theory–Based Short Forms to Measure the Social Impact of Burn Injuries

Objective

To develop self-reported short forms for the Life Impact Burn Recovery Evaluation (LIBRE) Profile.

Ion Torrent ™ Genexus ™ Integrated Sequencer and ForeNGS Analysis Software—An automatic NGS-STR workflow from DNA to profile for forensic science

The Ion Torrent ™ Genexus ™ Sequencer (Genexus) is a highly integrated instrument that can automate library construction, templating, and sequencing in a single-instrument run. By programing the ForeNGS Analysis Software (FNAS), we bridged the gap between sequencing and genotyping without manual intervention. FNAS can automatically transfer sequencing output files from Genexus, analyze the repeat and flanking regions aligned to the GRCh38 assembly, name the alleles according to the ISFG guidelines, and generate user-friendly interactive profiles. Genexus and FNAS can accomplish the fully automatic DNA-to-Profile workflow in forensics. Based on our experiences, the optimal assay parameters on Genexus were validated as follows: 24 cycles of target amplification for library construction; 40 μL of library and 400 bp of template size for templating; 852 flows of dNTPs by order of Ion samba HID2 for sequencing; and 750,000 reads per sample at minimum for 16 samples multiplexed on a lane. By developmental validations of the Precision ID Globalfiler ™ NGS STR Panel v2, Genexus presented competitive performance at the optimal assay parameters qualified to detect commonly used forensic STR markers. It could produce repeatable and reproducible results, and human profiles could be easily separated from nonhuman profiles. Additionally, Genexus was sensitive enough to detect samples with 100 pg of input DNA, and it was suitable for various types of case samples, especially for low copy number samples and degraded samples. Moreover, minor contributors could be detected between the 4:1 and 1:4 mixtures with an analysis threshold of 50 × . The Genexus workflow is a robust and labor-effective solution enabling forensic scientists to obtain NGS-STR profiles within a single day and with only the need to prepare DNA extracts, then set up Genexus, and finally interpret profiles on FNAS.     

胃冠状、胃短静脉栓塞术对胃底静脉曲张出血疗效评价

目的探讨胃冠状静脉、胃短静脉栓塞术对胃底静脉曲张出血治疗的价值。方法32例肝硬化并食管胃底静脉曲张出血经内镜下套扎、硬化治疗后仍有出血的患者，经皮经肝穿刺行胃冠状静脉、胃短静脉栓塞治疗。栓塞剂主要为无水乙醇、钢圈和明胶海绵。均行1次栓塞治疗，并经3～11个月随访，胃镜复查。结果29例复查胃镜，其中21例(72．4％)胃底曲张静脉完全消失，8例(27．6％)胃底曲张静脉明显减轻，无红色征及糜烂。随访期内有1例(3．1％)因门脉高压性胃炎致黏膜糜烂出血。未发现明显并发症。结论经皮经肝穿刺行胃冠状静脉、胃短静脉栓塞治疗具有消除胃底静脉曲张，并可预防出血的作用。     

Glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with chronic HCV genotypes 1–6 and compensated cirrhosis: The EXPEDITION-8 trial

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Linear lesions for treating the recurrence of persistent atrial tachyarrhythmia after cryoballoon ablation of atrial fibrillation

Overall, 133 patients underwent 170 procedures for the treatment of persistent ATa following an index cryoballoon pulmonary vein isolation (n = 715). After all the procedures, > 90% of the patients had a roof line, a mitral isthmus and/or septal line, and a cavotricuspid isthmus line. Ninety-two patients (69.2%) were in sinus rhythm after a median of 36 months since the index cryoballoon PVI. ATa: atrial tachyarrhythmia; cryo: cryoballoon; CTI: cavotricuspid isthmus; LSPV: left superior pulmonary vein; LIPV: left inferior pulmonary vein; PVI: pulmonary vein isolation; RF: radiofrequency; RSPV: right superior pulmonary vein; RIPV: right inferior pulmonary vein.

     

Mechanisms of intestinal failure in Crohn's disease

PURPOSE: The purpose of this study was to determine the mechanisms by which patients with Crohn's disease develop intestinal failure and, in particular, to assess the relative importance of severe primary disease, repeated uncomplicated elective small intestine resection, and resection performed as a consequence of intra-abdominal septic surgical complications. METHODS: This was a retrospective analysis of 41 patients with Crohn's disease referred to a specialized intestinal failure unit between January 1987 and September 1998 for permanent home parenteral nutrition. To compare the surgical activity in patient groups, a resection index was calculated by dividing the number of intestinal resections by the interval in years between the first resection for Crohn's disease and referral for management of intestinal failure. RESULTS: Extensive primary Crohn's disease was responsible for intestinal failure in 7 cases (17 percent). The remainder (n=34, 83 percent) developed intestinal failure after intestinal resection. Nine of the surgical Crohn's patients developed intestinal failure after uncomplicated sequential resection, (median small-bowel length 65 (range, 60–120) cm) after a median of 3 (range, 2–8) operations over a median of 17 (range, 3–27) years. By contrast, the other 25 surgical Crohn's patients developed intestinal failure after multiple unplanned laparotomies for intra-abdominal sepsis (median small-bowel length 70 (range, 60–200) cm), with a median of 4 (range, 2–7) laparotomies performed over a median of 0.5 (range, 0.1 to 1.5) years (P<0.001). The resection index for the 25 Crohn's patients undergoing laparotomies for intra-abdominal sepsis was significantly greater than that of the 9 patients who had planned sequential resections (2.1 (0.27–25)vs. 0.23 (0.1–1.0);P < 0.002, Mann-WhitneyU test). CONCLUSION: Intestinal failure develops in Crohn's disease primarily as a result of complications of surgical treatment. The largest group of patients at risk consists of those who are undergoing multiple unplanned laparotomies to control intra-abdominal sepsis.     

溴吡斯的明与左旋多巴联合激发试验峰值时间的探讨

目的：探讨溴吡斯的明与左旋多巴在生长激素（GH）激发试验中应用及峰值出现时间,以减少多次采血给患儿带来的痛苦。方法：选取2018年1-8月在我科就诊的需接受溴吡斯的明与左旋多巴联合激发试验的矮小症患儿88例,对生长激素峰值出现时间进行分析。结果：生长激素峰值出现在药物联合应用后30~60 min的患儿共69例（78.41%）,其中在用药后60 min出现峰值的患儿达40例（45.45%）,而在用药后90~120 min出现峰值的患儿仅14例（15.91%）,与30~60 min出现峰值的患儿数比较差异有统计学意义（χ2=68.97,P<0.01）。结论：溴吡斯的明与左旋多巴联合激发试验在药物联合应用后30~60 min出现峰值较多,90~120 min出现峰值较少,为减少患儿痛苦,可减少用药后120 min抽血次数,该结论可在临床推广。