Background: and Purpose Whole-exome sequencing (WES) is a valuable tool for identifying causative mutations in adult moyamoya disease (MMD), thereby advancing our understanding of the genetic mechanisms underlying this condition. Here, we conducted the first WESbased association study aimed at identifying genetic modifiers implicated in MMD. Methods: This WES study involved 160 patients with MMD and 189 controls from a multicenter hospital-based biobank, and evaluated combined annotation-dependent depletion (CADD) scores. Mutant-allele frequencies were compared in 369,121 individuals derived from the UK Biobank (UKB) WES. Mutant-allele risk scores (MARSs) were created based on WESidentified mutations. Gene-based association analyses and pooled analyses in East-Asian populations were further performed. Results: Fourteen mutations reached the genome-wide significance criterion (p<5×10-8 ), among which the p.R4810K mutation in the ring finger protein 213 gene (RNF213) showed the strongest significance (odds ratio=117.4, p=8.54×10-24 ). Notably, two mutations—p.G576S (alpha-glucosidase [GAA]) and p.D54N (charged multivesicular body protein 6 [CHMP6])— exhibited high CADD scores of 32 and 25, respectively, whereas the RNF213 p.R4810K mutation demonstrated a moderate deleteriousness score of 10.63. Fourteen mutations exhibited significant differences in allele frequencies between patients and UKB controlled data (p<1×10-8 ).The MARS9 model (incorporating nine missense mutations) showed better predictability for MMD (90.89%). The analysis of gene-based associations revealed four candidate genes: GAA, RNF213, CHMP6, and CARD14 (p=5×10-19 to 4×10-7 ). The subsequent pooled analyses validated four mutations in East Asian populations: p.V1195M, p.D1331G, p.S2334N, and p.R4810K (p<3×10-8 ). Conclusions This pioneering study has corroborated the significance of p.R4810K and identified several causative mutations predisposing patients to MMD, which helps to improve the understanding of its polygenetic nature.

Surgical treatment of refractory and extensive cerebral venous sinus thrombosis (CVST) has limited applications. Here, we describe an open, direct sinus thrombectomy in the early phase of extensive CVST. A 49-year-old man with extensive CVST that occurred after the coronavirus disease 2019 (COVID-19) vaccination and affected the drainage of the Labbé vein presented with clinical deterioration and left temporal hemorrhagic infarction. Since the patient had extensive CVST, we determined that systemic anticoagulation and endovascular treatment were not suitable treatment options. Therefore, we decided on an emergency surgical treatment and performed direct surgical thrombectomy. We followed extended suboccipital approach and made multiple incisions on the sinuses, exposing the posterior superior sagittal sinus to the transverse sigmoid junction. Consequently, the clinical condition of the patient dramatically improved, resulting in a favorable outcome with a modified Rankin scale score of 0. Performing emergency open surgical thrombectomy was a technically feasible treatment option that recanalize obstructed sinuses. Importantly, the patient recovered with a good clinical outcome. Early maximal surgical thrombectomy can be an effective and lifesaving method to treat extensive CVST with hemorrhagic infarction.

PURPOSE: To determine whether preoperative CT is helpful in predicting the development of recurrent tumor following surgical resection in patients with esophageal cancer. MATERIALS AND METHODS: Thirty patients with esophageal cancer in whom preoperative CT of the chest had been performed were included in the study. All had undergone esophagectomy, esophagogastrostomy and lymph node dissection at our institution between 1995 and 1997. They were divided into two groups according to the development of tumor recurrence during the follow-up period of three years. Sixteen patients (group I) suffered tumor recurrence, while the other 14 (group II) remained tumor-free after surgery. In each group, a review of the preoperative CT scans indicated the length, thickness, location and margin of the tumor, and the presence or absence of lymphadenopathy in the mediastinum and/or upper abdomen. Differences in preoperative CT findings between the two groups were assessed by statistical testing. RESULTS: Lymphadenopathy of the mediastinum and/or upper abdomen was seen in 11 (69%) of 16 patients in group I and three (21%) of 14 in group II (p<.05). The tumor margin was indistinct in seven patients (44%) in group I and in one (7%) in group II (p<.05). The average length and thickness of esophageal tumors were 5.2 and 1.4 cm, respectively, in group I, and 3.5 and 1.5 cm, respectively, in group II (p>.05). In group I, five esophageal tumors were located in the middle esophagus and eleven in the lower esophagus. In group II, such tumor was located one in the upper esophagus, six in the middle esophagus, and seven in the lower esophagus (p>.05). CONCLUSION: Patients with preoperative CT findings of lymphadenopathy and/or an indistinct primary tumor margin are more likely to develop tumor recurrence following surgical resection than those without these findings.
Abdomen ; Esophageal Neoplasms ; Esophagectomy ; Esophagus ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymphatic Diseases ; Mediastinum ; Recurrence* ; Thorax ; Tomography, X-Ray Computed