Genetic correlation, shared loci, but no causality between bipolar disorder and inflammatory bowel disease: A genome-wide pleiotropic analysis.

BACKGROUND AND AIMS: The comorbidity between bipolar disorder (BD) and inflammatory bowel disease (IBD) has been widely reported in observational studies. However, unclear whether this comorbidity reflects a shared genetic architecture. METHODS: Leveraging large-scale genome-wide association study (GWAS) summary statistics of BD, IBD and its subtypes, ulcerative colitis (UC) and Crohn's disease (CD), we performed a genome-wide pleiotropic analysis to estimate heritability and genetic correlation, identify pleiotropy loci/genes, and explore the shared biological pathway. Mendelian randomization (MR) studies were subsequently employed to infer whether the potential causal relationship is present. RESULTS: We found a positive significant genetic correlation between BD and IBD (rg = 0.10, P = 7.00 × 10-4), UC (rg = 0.09, P = 2.90 × 10-3), CD (rg = 0.08, P = 6.10 × 10-3). In cross-trait meta-analysis, a total of 29, 24, and 23 independent SNPs passed the threshold for significant association between BD and IBD, UC, and CD, respectively. We identified five novel pleiotropy genes including ZDHHC2, SCRN1, INPP4B, C1orf123, and BRD3 in both BD and IBD, as well as in its subtypes UC and CD. Pathway enrichment analyses revealed that those pleiotropy genes were mainly enriched in several immune-related signal transduction pathways and cerebral disease-related pathways. MR analyses provided no evidence for a causal relationship between BD and IBD. CONCLUSION: Our findings corroborated that shared genetic basis and common biological pathways may explain the comorbidity of BD and IBD. These findings further our understanding of shared genetic mechanisms underlying BD and IBD, and potentially provide points of intervention that may allow the development of new therapies for these co-occurrent disorders.

L1 cell adhesion molecule high expression is associated with poor prognosis in surgically resected brain metastases from lung adenocarcinoma.

OBJECTIVES: Accurate prognosis assessment across the heterogeneous population of brain metastases is very important, which may facilitate clinical decision-making and appropriate stratification of future clinical trials. Previous studies have shown the L1 Cell Adhesion Molecule (L1CAM) is potentially involved in human malignancies of multiple different samples and unfavorable survival. However, no data of L1CAM are available for the brain metastases from lung adenocarcinoma, especially for the one with neurosurgical resection. METHOD: The authors investigated the L1CAM expression in cranial metastatic lesions for patients with brain metastases from lung adenocarcinoma after neurosurgical resection using tissue microarrays that were obtained from the Department of Neurosurgery at the Cancer Hospital of the Chinese Academy of Medical Sciences. Furthermore, the relationship between L1CAM expression and clinic-pathological parameters, including overall survival time, was analyzed to assess the prognostic value of L1CAM. RESULTS: L1CAM high expression was found in 62.30% of brain metastases from lung adenocarcinoma and significantly correlated with brain metastasis number (p = 0.028) and Lung-molGPA score (p = 0.042). Moreover, L1CAM expression was an independent predictor of survival for brain metastases after neurosurgical resection in a multivariate analysis. Patients with L1CAM high expression had unfavorable overall survival time (p = 0.016). In addition, the multivariate analysis also showed age and extracranial transfer were also the independent prognostic factors for this type of patient with brain metastases. CONCLUSIONS: A subset of brain metastases from lung adenocarcinoma aberrantly expresses L1CAM. L1CAM is a novel independent prognostic factor for brain metastasis from lung adenocarcinoma after neurosurgical resection.

L1 cell adhesion molecule high expression is associated with poor prognosis in surgically resected brain metastases from lung adenocarcinoma

Abstract Objectives Accurate prognosis assessment across the heterogeneous population of brain metastases is very important, which may facilitate clinical decision-making and appropriate stratification of future clinical trials. Previous studies have shown the L1 Cell Adhesion Molecule (L1CAM) is potentially involved in human malignancies of multiple different samples and unfavorable survival. However, no data of L1CAM are available for the brain metastases from lung adenocarcinoma, especially for the one with neurosurgical resection. Method The authors investigated the L1CAM expression in cranial metastatic lesions for patients with brain metastases from lung adenocarcinoma after neurosurgical resection using tissue microarrays that were obtained from the Department of Neurosurgery at the Cancer Hospital of the Chinese Academy of Medical Sciences. Furthermore, the relationship between L1CAM expression and clinic-pathological parameters, including overall survival time, was analyzed to assess the prognostic value of L1CAM. Results L1CAM high expression was found in 62.30% of brain metastases from lung adenocarcinoma and significantly correlated with brain metastasis number (p = 0.028) and Lung-molGPA score (p = 0.042). Moreover, L1CAM expression was an independent predictor of survival for brain metastases after neurosurgical resection in a multivariate analysis. Patients with L1CAM high expression had unfavorable overall survival time (p = 0.016). In addition, the multivariate analysis also showed age and extracranial transfer were also the independent prognostic factors for this type of patient with brain metastases. Conclusions A subset of brain metastases from lung adenocarcinoma aberrantly expresses L1CAM. L1CAM is a novel independent prognostic factor for brain metastasis from lung adenocarcinoma after neurosurgical resection.

Medium-term efficacy of arthroscopic debridement vs conservative treatment for knee osteoarthritis of Kellgren-Lawrence grades I-III.

BACKGROUND: Arthroscopic debridement is a mature treatment for knee osteoarthritis (KOA). Due to the differences in the research subjects, methods, and efficacy evaluation indexes, there are great differences in the surgical efficacy reported in the literature. AIM: To compare the medium-term efficacy of arthroscopic debridement and conservative treatment for KOA of Kellgren-Lawrence grades I-III. METHODS: Patients with KOA of Kellgren-Lawrence grades I-III who were admitted to the orthopedic clinic of our hospital from July 2018 to December 2018 and agreed to undergo arthroscopic surgery were included in an arthroscopic debridement group, and those who refused surgical treatment were included in a conservative treatment group. Gender, age, body mass index (BMI), side of KOA, American hospital for special surgery knee score (HSS score) before treatment, visual analogue scale (VAS) score during walking and rest before treatment, conservative treatment content, and surgical procedure were recorded. Outpatient visits were conducted at the 1st, 3rd, 6th, 12th, and 24th mo after treatment in the two groups. The changes of HSS score and VAS score in each group before and after treatment were statistically analyzed, and the differences of HSS score and VAS score in different treatment stages between the two groups were also compared. RESULTS: In the conservative treatment group, there were 80 patients with complete follow-up data, including 20 males and 60 females, aged 58.75 ± 14.66 years old. And in the knee arthroscopic debridement group, there were 98 patients with complete follow-up data, including 24 males and 74 females, aged 59.27 ± 14.48 years old. There was no statistically significant difference in the general data (gender, age, BMI, side of KOA, Kellgren-Lawrence grade distribution, HSS score, and VAS score) between the two groups before treatment. The HSS scores of the conservative treatment group at the 1st, 3rd, 6th, 12th, and 24th mo after treatment were significantly higher than that before treatment (P < 0.05). There was no statistical difference in HSS score of the conservative treatment group among the 1st, 3rd, 6th, 12th, and 24th mo (P > 0.05). The HSS score of the knee arthroscopic debridement group at the 1st mo after surgery was significantly higher than that before surgery (P < 0.05). HSS scores of the knee arthroscopic debridement group at the 3rd, 6th, 12th, and 24th mo were significantly higher than those before surgery and at the 1st mo after surgery (P < 0.05). There were no statistically significant differences in HSS scores at the 3rd, 6th, 12th, and 24th mo after surgery (P > 0.05). HSS scores at the 3rd, 6th, 12th, and 24th mo were significantly higher in the arthroscopic debridement group than in the conservative treatment group (P < 0.05). There was no statistical difference in HSS scores between the two groups before treatment and at the 1st mo of follow-up (P > 0.05). VAS scores during walking and rest were significantly decreased in both groups, and the VAS score during rest was significantly lower in the arthroscopic debridement group than in the conservative treatment group, but there was no significant difference in the VAS score during walking between the two groups after treatment. CONCLUSION: Compared with conservative treatment, arthroscopic debridement can significantly improve the knee resting pain and knee functional status of patients with KOA of Kellgren-Lawrence grades I-III within 2 years after treatment.