Gastric poorly cohesive carcinoma: a correlative study of mutational signatures and prognostic significance based on histopathological subtypes.

AIMS: Genome-wide next-generation sequencing has revealed several driver mutations and has allowed the establishment of a molecular taxonomy of gastric cancer. However, there are few detailed studies on the mutational spectrum of poorly cohesive gastric carcinoma. Thus, this study aim to investigate its mutation profile based on clinicopathological characteristics. METHODS AND RESULTS: Herein, we analysed the mutational pattern of 77 genes in a cohort of 91 patients with poorly cohesive carcinoma by using targeted sequencing, and evaluated the clinicopathological significance of the various mutations based on histological pattern, either signet ring cell (SRC) or other types of poorly cohesive carcinoma (not otherwise specified) (PCC-NOS). Panels of seven (PIK3CA, CDH1, PTEN, RHOA, HDCA9, KRAS, and ATM), three (PIK3CA, CTNNB1, and KRAS) and two (HDCA9 and IGF1R) genes were associated with a diffuse infiltrative growth pattern, lymphovascular invasion, and perineural invasion, respectively. Furthermore, PDGFRB mutations were associated with a favourable prognosis, whereas MET mutations were associated with a poor prognosis. The PCC-NOS-predominant type was associated with a greater depth of invasion, lymph node metastasis and poorer prognosis than the SRC-predominant type. Mutations in TP53, BRAF, PI3CA, SMAD4 and RHOA were associated with PCC-NOS. Interestingly, RHOA-mutated gastric cancers showed a distinct morphology, as they were characterised by a superficial SRC or tubular component and a deep invasive PCC-NOS component with desmoplasia. CONCLUSIONS: Taken together, our findings demonstrate that gastric poorly cohesive carcinomas show several mutational patterns associated with specific clinicopathological characteristics, and particularly show distinct morphological findings when associated with RHOA mutation.

Reliability and validity testing of automated scoring in obstructive sleep apnea diagnosis with the Embletta X100.

OBJECTIVES/HYPOTHESIS: To verify the reliability and validity of automated scoring and compare it to that of manual scoring for diagnosing obstructive sleep apnea using an Embletta X100 level 2 portable device. STUDY DESIGN: Retrospective study. METHODS: A total of 116 patients with suspected obstructive sleep apnea who had successfully received portable polysomnography with the Embletta X100 were examined. All polysomnography data were analyzed by automated and manual methods. Manual scoring was performed according to the revised American Academy of Sleep Medicine 2012 criteria. Automated scoring was analyzed using the automatic algorithm, which was updated with the American Academy of Sleep Medicine 2012 criteria. All parameters were evaluated statistically using correlation analysis and paired t tests. RESULTS: The apnea-hypopnea index for automated scoring and manual scoring with the Embletta X100 were moderately correlated (r = 0.76, P < .001). However, there was poor agreement (Bland-Altman plot, κ = 0.34, 0.33, and 0.26; cutoff value = 5, 15, and 30), and the apnea-hypopnea index data were generally excessively underestimated based on diagnostic agreement and disagreement criteria. Furthermore, the apnea-hypopnea index severity (Kendall tau-b = 0.62) between automated and manual scoring lacked good concordance. CONCLUSIONS: Automated scoring using the Embletta X100 was statistically moderately related to the manual scoring results. However, automated scoring tended to excessively underestimate the apnea-hypopnea index data compared to manual scoring. Thus, manual scoring by a sleep expert is essential for obstructive sleep apnea diagnosis with the Embletta X100. LEVEL OF EVIDENCE: 4.

Barefoot stubbing injuries to the great toe in children: a new classification by injury mechanism.

OBJECTIVE: This study was conducted to categorize barefoot stubbing injuries to the great toe in children by injury mechanism to differentiate benign stubbing injuries from more complex injuries necessitating surgery. DESIGN: Prospective clinical series of consecutively treated patients. SETTING: Tertiary university hospital setting. PATIENTS: Forty-one children who had sustained an indirect injury to the great toe during barefoot sports activities between January 2001 and December 2009 were included. INTERVENTION: Conservative or surgical treatment was done according to clinical and radiological findings. MAIN OUTCOME MEASUREMENT: Information regarding injury mechanism was collected from patients, parents, and coaches using skeletal models and assessed by a pediatric orthopedic surgeon. Mechanisms of injury were identified and grouped as follows: hyperabduction-flexion, hyperflexion, hyperabduction-extension, hyperextension, and hyperextension-adduction. RESULTS: Hyperabduction-flexion was the most common mechanism (n = 16), in which interphalangeal joint dislocation and skin disruption was noted in most cases. The second most common mechanism was hyperabduction-extension (n = 14) in which avulsion fracture of the lateral volar condyle of the proximal phalanx was noted in most cases. This avulsion fracture had the worst prognosis after conservative care. CONCLUSIONS: Based on these results, we have created a grading system and treatment protocol for indirect hallux sports injuries in children. Avulsion fracture of the lateral condyle of the proximal phalanx, a result of hyperabduction-extension, is a high-risk sign of nonunion and should be aggressively treated, contrary to previous guidelines. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.