Purpose: Patients with digestive system cancers (DSCs) are at a high risk for hospitalizations; however, the risk factors for readmission remain unknown. Here, we established a retrospective cohort study to assess the association between metabolic obesity phenotypes and readmission risks of DSC.Experimental design: A total of 142,753 and 74,566 patients at index hospitalization were ultimately selected from the Nationwide Readmissions Database (NRD) 2018 to establish the 30-day and 180-day readmission cohorts, respectively. The study population was classified into four groups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). Multivariate Cox regression analysis was used to estimate the effect of metabolic obesity phenotypes on DSC readmission.Results: The MUNO phenotype had 1.147-fold (95% CI: 1.066, 1.235; p < 0.001) increased 180-day readmission risks in patients with neoplasm of the upper digestive tract. The MUNO phenotype had 1.073-fold (95% CI: 1.027, 1.121; p = 0.002) increased 30-day readmission risks and 1.067-fold (95% CI: 1.021, 1.115; p = 0.004) increased 180-day readmission risks in patients with neoplasm of the lower digestive tract. The MUNO and MUO phenotypes were independent risk factors of readmission in patients with liver or pancreatic neoplasm. Metabolic obesity status was independently associated with a high risk of severe and unplanned hospitalization within 30 days or 180 days.Conclusion: Both obesity and metabolic abnormalities are associated with a high risk for the poor prognosis of DSC patients. The effect of metabolic categories on the short- or long-term readmission of liver or pancreas cancers may be stronger than that of obesity.

Background. Kallmann syndrome (KS) is a rare genetic disease characterized by the reproductive system and olfactory dysplasia due to the defective migration of gonadotropin-releasing hormone (GnRH) neurons. However, this disorder is clinically heterogeneous and the genotype-phenotype relationship has not been determined. Objective. The present study aimed to identify the variant causing KS in a Chinese family and evaluate the functional consequences and phenotypes associated with the novel variant. Methods. A Chinese family with KS was screened for pathogenic variants by whole-exome sequencing (WES). Bioinformatic analysis was performed to predict the consequences of the identified variant. The expression of the mutant protein was examined in vitro. Results. A novel heterozygous variant (NM_006080.2:c.814G>T) in SEMA3A was identified in the patient and his father, which caused the substitution of aspartic acid with tyrosine in codon 272. It was predicted to result in pathogenic significance with a high damaging score and seriously affect protein structure by bioinformatic analysis. In vitro experiments revealed this variant could significantly decrease the expression of SEMA3A. Furthermore, it may cause the disease by failing to induce the phosphorylation of focal adhesion kinase (FAK) in GnRH neurons. Conclusion. Identification and functional characterization of this novel variant in the SEMA3A gene in a Chinese family with Kallmann syndrome extend the genetic variant spectrum of SEMA3A and provide more data about the heterogeneity of KS, which may provide further insights into the diagnosis of KS and help patients get additional data in genetic counseling and timely treatment.

Background and aims: Regional muscle distribution is associated with abdominal obesity and metabolic syndrome. However, the relationship between muscle distribution and nonalcoholic fatty liver disease (NAFLD) remains unclear. This study was to determine the relationship between regional muscle distribution and the risk and severity of NAFLD. Methods: This cross-sectional study ultimately included 3161 participants. NAFLD diagnosed by ultrasonography was classified into three groups (non, mild, and moderate/severe). We estimated the regional body muscle mass (lower limbs, upper limbs, extremities, and trunk) through multifrequency bioelectrical impedance analysis (BIA). The relative muscle mass was defined as the muscle mass adjusted for the body mass index (BMI). Results: NAFLD participants accounted for 29.9% (945) of the study’s population. Individuals with a higher lower limb, extremity, and trunk muscle mass had a lower risk of NAFLD (p < 0.001). Patients with moderate/severe NAFLD had a lower muscle mass of the lower limbs and trunk than patients with mild NAFLD (p < 0.001), while the muscle mass of the upper limbs and extremities did not differ significantly between the two groups. Moreover, similar results were found for both sexes and among different age groups. Conclusions: A higher muscle mass of the lower limbs, extremities, and trunk was negatively associated with the risk of NAFLD. A lower muscle mass of the limbs and trunk was inversely associated with the severity of NAFLD. This study provides a new theoretical basis for the development of individualized exercise prescriptions for the prevention of NAFLD in non-NAFLD patients.

Introduction: This study aimed to examine the risk of common diseases among people with pre-diabetes and explored the relationship between pre-diabetes and multimorbidity (in this case, two or more comorbid diseases). Methods: An observational multicohort study using data from the UK Biobank database and the National Inpatient Sample (NIS) database (2016–2018) was conducted. We analysed 461 535 participants and 17 548 442 patients aged 18 years or older from both databases, of whom 14.0% and 0.7% were diagnosed with pre-diabetes, respectively. A total of 76 common diseases of various body systems were selected as adverse health outcomes for analysis. Results: Among 64 523 individuals with pre-diabetes in the UK Biobank, the mean age was 60 years, 35 304 (54.7%) were female. There were 24 non-overlapping diseases associated with pre-diabetes with significant multiple test results in both databases, and most of them are circulatory system diseases. Compared with normoglycaemia, the confounder-adjusted HR in the UK Biobank for pre-diabetes was 1.46 (95% CI 1.43 to 1.49) for accompanying complex multimorbidity (ie, four or more pre-diabetes-related diseases), the corresponding confounder-adjusted OR in the NIS study was 10.03 (95% CI 9.66 to 10.40). Conclusion: Pre-diabetes was associated with a significantly higher risk of multimorbidity. Pre-diabetes, thus, might represent an important target for multimorbidity prevention, and stronger emphasis on its management seems necessary to reduce the risk of the development of multiple comorbidities, especially before the onset of overt diabetes.

(1) Background: As the introduction of “positive” diagnostic criteria for metabolic dysfunction-associated fatty liver disease (MAFLD) does not exclude alcohol consumption, some patients originally diagnosed with alcoholic fatty liver disease (AFLD) may be diagnosed with dual- etiology fatty liver disease (AFLD&MAFLD), which requires us to urgently explore the impact of the changes in this classification of AFLD on clinical manifestations. (2) Methods: Utilizing data from the Nationwide Inpatient Sample database 2016–2018, a total of 9269 participants with AFLD were selected. With the definition of MAFLD, these patients were further categorized into two groups: single AFLD and AFLD&MAFLD. The primary outcome was the risk of comorbidities and organ failures. The secondary outcomes were the length of stay, total charges, and in-hospital all-cause mortality. (3) Results: The patients with AFLD&MAFLD were older, were predominantly male, and had more comorbidities and organ failures compared to the patients with AFLD. These comorbidities included coronary atherosclerosis, myocardial infarction, cerebrovascular disease, arrhythmia, asthma, chronic obstructive pulmonary disease, and chronic kidney disease (all p values < 0.05). The patients with AFLD&MAFLD were more likely to develop acute and chronic heart and/or kidney failures than those with single AFLD (all p < 0.05). The length of stay and total charges of the patients in the AFLD&MAFLD group were greater than the single AFLD group (p = 0.029 and p < 0.001, respectively). No significant difference in all-cause mortality was observed. (4) Conclusions: The patients with AFLD&MAFLD have more comorbidities and organ failures, longer hospital stays, and higher hospitalization costs than the patients with single AFLD. Hence, patients with dual-etiology fatty liver disease deserve more attention from clinical staff during treatment.

Background: Immunodeficiency diseases (IDDs) are associated with an increased proportion of cancer-related morbidity. However, the relationship between IDDs and malignancy readmissions has not been well described. Understanding this relationship could help us to develop a more reasonable discharge plan in the special tumor population. Methods: Using the Nationwide Readmissions Database, we established a retrospective cohort study that included patients with the 16 most common malignancies, and we defined two groups: non-immunodeficiency diseases (NOIDDs) and IDDs. Results: To identify whether the presence or absence of IDDs was associated with readmission, we identified 603,831 patients with malignancies at their time of readmission in which 0.8% had IDDs and in which readmission occurred in 47.3%. Compared with NOIDDs, patients with IDDs had a higher risk of 30-day (hazard ratio (HR) of 1.32; 95% CI of 1.25–1.40), 90-day (HR of 1.27; 95% CI of 1.21–1.34) and 180-day readmission (HR of 1.28; 95% CI of 1.22–1.35). More than one third (37.9%) of patients with IDDs had readmissions that occurred within 30 days and most (82.4%) of them were UPRs. An IDD was an independent risk factor for readmission in patients with colorectal cancer (HR of 1.32; 95% CI of 1.01–1.72), lung cancer (HR of 1.23; 95% CI of 1.02–1.48), non-Hodgkin’s lymphoma (NHL) (HR of 1.16; 95% CI of 1.04–1.28), prostate cancer (HR of 1.45; 95% CI of 1.07–1.96) or stomach cancer (HR of 2.34; 95% CI of 1.33–4.14). Anemia (44.2%), bacterial infections (28.6%) and pneumonia (13.9%) were the 30-day UPR causes in these populations. (4) Conclusions: IDDs were independently associated with higher readmission risks for some malignant tumors. Strategies should be considered to prevent the causes of readmission as a post discharge plan.