Hospitalisations with infectious disease diagnoses in somatic healthcare between 1998 and 2019: A nationwide, register-based study in Swedish adults.

Background: Several studies indicate increasing hospitalisation rates for specific infectious diseases (IDs). Studies describing the entire ID spectrum are scarcer. Our aim was to describe hospital use with ID diagnoses in Swedish adults from 1998 to 2019. Methods: All four-position codes in ICD-10 were reclassified as ID or non-ID diagnoses. Using data from the National Patient Register, age-standardised hospitalisation rates and average length-of-stay (LOS) was determined for hospitalisations with ID vs non-ID diagnoses in the primary position at discharge. The 22-year study period was divided into five periods that were compared using standardised rate ratios (SRR). Findings: Annual hospitalisations with ID diagnoses increased from 115 thousand in 1998-2002 to 182 thousand in 2015-2019, for a rate increase from 17·4 to 23.0 per 1000 person-years, and a SRR (95%CI) of 1.32 (1.32-1.33). Concurrently, the hospitalisation rate with non-ID diagnoses decreased from 147 to 110, for a SRR of 0.75 (0.75-0.75). Average LOS decreased less for IDs than for non-IDs. Consequently, the proportion of hospital nights for which an ID was considered causing the hospitalisation increased from 11% to 21%. Persons aged 80+ years had the highest ID hospitalisation rate. Interpretation: The increased hospital use with ID diagnoses suggests an increasing incidence of severe IDs as well as a changing case-mix of hospitalised patients. Given the anticipated demographic change, this trend is likely to persist. Healthcare systems will need to address IDs in a comprehensive and standardised way. Funding: Governmental Funding of Research within the Clinical Sciences (ALF).

Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma / 医学前沿

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

The relationship between the metabolic syndrome and arterial wall thickness: A mosaic still to be interpreted.

BACKGROUND AND AIMS: We aimed to identify clusters of metabolic syndrome (MetS) components, risky for extremely high intima-media thickness. METHODS: We studied 41,513 volunteers (men and women) from eleven cohorts worldwide, participating in the MARE (Metabolic syndrome and Artery REsearch) Consortium. RESULTS: Specific clusters of MetS components - high triglycerides-high blood pressure-abdominal obesity (TBW), low HDL cholesterol-high blood pressure-abdominal obesity (HBW), high glucose-high blood pressure-abdominal obesity (GBW) - were accompanied by a 50-90% significantly greater likelihood of presenting extremely high intima-media thickness (via ultrasound of carotid artery, CCA IMT), after controlling for age, sex, smoking, non-HDL cholesterol, and presence of diabetes mellitus. This likelihood is comparable to the effect of being 7-8 years older or of being a cigarette smoker or of having non-HDL cholesterol 50 mg/dl higher. CONCLUSIONS: The consistent association of specific clusters of MetS components with extremely thick (older) large artery cross-culturally suggests that identification of those clusters in clinical practice will facilitate a personalized health care and a better - i.e. more healthy and cost-effective - prevention of major cardiovascular (CV) events.