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Study Question: Is a maternal history of spontaneous abortion (SA) associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring?Summary Answer: Our results suggest an association between maternal history of SA and ADHD in offspring, with the risk increasing with the number of maternal SA and highest in the firstborn children whose mothers had had recurrent SAs after adjusting for a number of potential confounders.What Is Known Already: A history of SA has been associated with more complications in next pregnancies and adverse childbirth outcomes, which are risk factors for ADHD in the offspring. However, no previous study has investigated whether maternal SA increases risk of ADHD in the offspring.Study Design, Size, Duration: This population-based study included all live-born children in Denmark from 1 January 1995 to 31 December 2012 (n = 1 062 667). All children were followed from 3 years of age until the day of ADHD diagnosis, death, emigration or 31 December 2016, whichever came first.Participants/materials, Setting, Methods: There were 130 206 (12.2%) children born to mothers who had at least one SA. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).Main Results and the Role Of Chance: During a median follow-up of 9.4 years (interquartile range, 5.4-14.3), 25 747 children were diagnosed with ADHD. Overall, children of mothers with a history of SA had an increased rate of ADHD (HR, 1.11; 95% CI, 1.07 to 1.15). The HRs increased with the number of maternal SA, 1.09 (95% CI, 1.05 to 1.13) for one SA and 1.22 (95% CI, 1.12 to 1.33) for at least two SAs, respectively. These findings were consistent when we took into consideration a number of factors, such as maternal socioeconomic status, type of SA, birth order, parental history of psychiatric disorders, pregnancy characteristics and adverse birth outcomes.Limitations, Reasons For Caution: Misclassification of SA was possible as we used population-based register data to capture maternal history of SA. However, any misclassification of maternal history of SA would be non-differential with regard to the diagnosis of ADHD in offspring, which generally leads to underestimation of the associations. Furthermore, probabilistic sensitivity analysis suggested that only 1% of change in the estimate may have been due to misclassification of SA.Wider Implications Of the Findings: SA is quite frequent (varying from 15 to 20%), and a small increase of neurodevelopmental problems in offspring could have major public health implications.Study Funding/competing Interest(s): This work was supported by grants from the National Natural Science Foundation of China (No. 81703237, No. 81530086 and No. 81761128035), National Key Research and Development Program (2018YFC1002801, 2016YFC1000505), Shanghai Municipal Commission of Health and Family Planning (No. 2017ZZ02026, No. 2017EKHWYX-02), the Novo Nordisk Foundation (NNF18OC0052029), the Danish Council for Independent Research (DFF-6110-00019), the Nordic Cancer Union (176673, 186200 and R217-A13234-18-S65), Karen Elise Jensens Fond (2016) and Xinhua Hospital of Shanghai Jiao Tong University School of Medicine (2018YJRC03). All authors report no conflict of interest.Trial Registration Number: NA. [ABSTRACT FROM AUTHOR]

Background: Whether extended lymphadenectomy for right colon cancer leads to increased perioperative complications or improves survival is still controversial. This trial aimed to compare the efficacy and safety of complete mesocolic excision (CME) versus D2 dissection in laparoscopic right hemicolectomy for patients with right colon cancer. This article reports the early safety results from the trial.Methods: This randomised, controlled, phase 3, superiority, trial was done at 17 hospitals in nine provinces of China. Eligible patients were aged 18-75 years with histologically confirmed primary adenocarcinoma located between the caecum and the right third of the transverse colon, without evidence of distant metastases. Central randomisation was done by means of the Clinical Information Management-Central Randomisation System via block randomisation (block size of four). Patients were randomly assigned (1:1) to CME or D2 dissection during laparoscopic right colectomy. Central lymph nodes were dissected in the CME but not in the D2 procedure. Neither investigators nor patients were masked to their group assignment but the quality control committee were masked to group assignment. The primary endpoint was 3-year disease-free survival, but the data for this endpoint are not yet mature; thus, only the secondary outcomes-intraoperative surgical complications and postoperative complications within 30 days of surgery, graded according to the Clavien-Dindo classification, mortality (death from any cause within 30 days of surgery), and central lymph node metastasis rate in the CME group only-are reported in this Article. This early analysis of safety was preplanned. The outcomes were analysed according to a modified intention-to-treat principle (excluding patients who no longer met inclusion criteria after surgery or who did not have surgery). This study is registered with ClinicalTrials.gov, NCT02619942. Study recruitment is complete, and follow-up is ongoing.Findings: Between Jan 11, 2016, and Dec 26, 2019, 1072 patients were enrolled and randomly assigned. After exclusion of 77 patients, 995 patients were included in the modified intention-to-treat population (495 in the CME group and 500 in the D2 dissection group). The postoperative surgical complication rate was 20% (97 of 495 patients) in the CME group versus 22% (109 of 500 patients) in the D2 group (difference, -2·2% [95% CI -7·2 to 2·8]; p=0·39); the frequency of Clavien-Dindo grade I-II complications were similar between groups (91 [18%] vs 92 [18%], difference, -0·0% [95% CI -4·8 to 4·8]; p=1·0) but Clavien-Dindo grade III-IV complications were significantly less frequent in the CME group than in the D2 group (six [1%] vs 17 [3%], -2·2% [-4·1 to -0·3]; p=0·022); no deaths occurred in either group. Of the intraoperative complications, vascular injury was significantly more common in the CME group than in the D2 group (15 [3%] vs six [1%], difference, 1·8 [95% CI 0·04 to 3·6]; p=0·045). Metastases in the central lymph nodes were detected in 13 (3%) of 394 patients who underwent central lymph node biopsy in the CME group; no patient had isolated metastases to central lymph nodes.Interpretation: Although the CME procedure might increase the risk of intraoperative vascular injury, it generally seems to be safe and feasible for experienced surgeons.Funding: The Capital Characteristic Clinical Project of Beijing and the Chinese Academy of Medical Sciences. [ABSTRACT FROM AUTHOR]

Background: The preoperative work-up has limitations on finding peritoneal dissemination (PD) in gastric cancer patients. Laparoscopic exploration (LE) can discover radiographically occult PD, obtain accurate stage and avert futile laparotomy. The aim of our study was to introduce "Four-Step Procedure" LE in West China Hospital and further evaluate its safety and feasibility.Methods: We conducted a retrospective analysis on 165 patients from July 2016 to December 2017 who underwent "Four-Step Procedure" LE in gastrointestinal surgery department of West China Hospital. All the patients were diagnosed with gastric adenocarcinoma without explicit distant metastasis through Computed Tomography and/or Gastrointestinal Ultrasonography. Peritoneal lavage cytological examination (CY) was routinely performed during LE in our research. The "Four-Step" technical process of LE was introduced comprehensively. The clinicopathologic features and the presence of PD or CY at LE were analyzed, and the stratified analysis by cT and cN stages on the proportion of P1 and/or CY1 was also reported in this study.Results: Total of 165 patients accepted LE in our study, among these patients: 27 (16.4%) patients with P1 and/or CY1: 19 (11.5%) patients were found PD (P1), 17 (10.3%) patients with positive cytological examination (CY1) and 9 (3.6%) patients with P1Cy1. The stratified analysis by cT stage indicated that there was no P1 and/or Cy1 in cT1-cT2 stages, 1 (2.7%) patient with P1 and 1 (2.7%) with Cy1 in cT3 stage, 18 (20.0%) patients with P1 and 16 (17.8%) with Cy1 in cT4 stage. After LE, there were 74 (44.8%) patients underwent laparoscopic assistant gastrectomy, 25 (15.2%) patients with open gastrectomy, 50 (30.3%) patients with neoadjuvant chemotherapy and 16 (9.7%) patients with palliative chemotherapy and/or conversion therapy.Conclusion: "Four-Step Procedure" LE is reliable and feasible for gastric cancer. From our study, LE has unique superiority on ascertaining PD and cytological examination and LE should be recommended in cT4 stage gastric cancer before resection. [ABSTRACT FROM AUTHOR]

Background: Staging laparoscopy(SL) is a recommended technique for the staging of Gastric Cancer(GC) and provides the indication for a radical surgery. Considering the medical practice in China, the standardized and regular usage of SL is yet to be spread. However, existing guidelines vary and make an ambiguity of indication for SL. Besides, the specific indication for Chinese patients remains a niche. This study aims to the essential, missing information of Chinese patients and tries to normalize the indication of LS in medical practice in China.Methods: The study is a prospective, multicenter cohort study being conducted in China with a total of 450 patients, all diagnosed with locally advanced gastric cancer (cT2-4 N0-3 M0, no evidence of intra-abdominal dissemination) through Computed Tomography(CT) and/or Endoscopic Ultrasonography(EUS). Peritoneal lavage is regularly performed during the SL. Multivariate Cox regression model and receiver-operator characteristic(ROC) analysis will be used to analyze the significant risk factors of intra-abdominal metastasis(including peritoneal dissemination and a positive cytological result).Discussion: This confirmatory study will provide us with the specific positive rate of intraabdominal metastasis of GC in China, compared with empirical evidence of 20%. We expect this trial will contribute to our discovery of the specific risk factors of intra-abdominal metastasis of Chinese patients and to the stimulating and performing of minimally invasive surgical procedures.Trial Registration: ClinicalTrials.gov : registration number NCT02172690 . [ABSTRACT FROM AUTHOR]

Background: Phelan-McDermid syndrome (PMS) or 22q13 deletion syndrome is a rare developmental disorder characterized by hypotonia, developmental delay (DD), intellectual disability (ID), autism spectrum disorder (ASD) and dysmorphic features. Most cases are caused by 22q13 deletions encompassing many genes including SHANK3. Phenotype comparisons between patients with SHANK3 mutations (or deletions only disrupt SHANK3) and 22q13 deletions encompassing more than SHANK3 gene are lacking.Methods: A total of 29 Mainland China patients were clinically and genetically evaluated. Data were obtained from medical record review and a standardized medical history questionnaire, and dysmorphology evaluation was conducted via photographic evaluation. We analyzed 22q13 deletions and SHANK3 small mutations and performed genotype-phenotype analysis to determine whether neurological features and other important clinical features are responsible for haploinsufficiency of SHANK3.Results: Nineteen patients with 22q13.3 deletions ranging in size from 34 kb to 8.7 Mb, one patient with terminal deletions and duplications, and nine patients with SHANK3 mutations were included. All mutations would cause loss-of function effect and six novel heterozygous variants, c.3838_3839insGG, c.3088delC, c.3526G > T, c.3372dupC, c.3120delC and c.3942delC, were firstly reported. Besides, we demonstrated speech delay (100%), DD/ID (88%), ASD (80%), hypotonia (83%) and hyperactivity (83%) were prominent clinical features. Finally, 100% of cases with monogenic SHANK3 deletion had hypotonia and there was no significant difference between loss of SHANK3 alone and deletions encompassing more than SHANK3 gene in the prevalence of hypotonia, DD/ID, ASD, increased pain tolerance, gait abnormalities, impulsiveness, repetitive behaviors, regression and nonstop crying which were high in loss of SHANK3 alone group.Conclusions: This is the first work describing a cohort of Mainland China patients broaden the clinical and molecular spectrum of PMS. Our findings support the effect of 22q13 deletions and SHANK3 point mutations on language impairment and several clinical manifestations, such as DD/ID. We also demonstrated SHANK3 haploinsufficiency was a major contributor to the neurological phenotypes of PMS and also responsible for other important phenotypes such as hypotonia, increased pain tolerance, impulsiveness, repetitive behaviors, regression and nonstop crying. [ABSTRACT FROM AUTHOR]