Background: Lipid metabolism plays an important role in viral infections. We aimed to assess the causal effect of lipid-lowering drugs (HMGCR inhibitiors, PCSK9 inhibitiors, and NPC1L1 inhibitior) on COVID-19 outcomes using two-sample Mendelian randomization (MR) study.Methods: We used two kinds of genetic instruments to proxy the exposure of lipid-lowering drugs, including expression quantitative trait loci of drugs target genes, and genetic variants within or nearby drugs target genes associated with low-density lipoprotein (LDL cholesterol from genome-wide association study). Summary-data-based MR (SMR) and inverse-variance-weighted MR (IVW-MR) were used to calculate the effect estimates.Results: SMR analysis found that a higher expression of HMGCR was associated with a higher risk of COVID-19 hospitalization (odds ratio [OR] = 1.38, 95% confidence interval [CI] = 1.06–1.81). Similarly, IVW-MR analysis observed a positive association between HMGCR-mediated LDL cholesterol and COVID-19 hospitalization (OR = 1.32, 95% CI = 1.00–1.74). No consistent evidence from both analyses was found for other associations.Conclusions: This two-sample MR study suggested a potential causal relationship between HMGCR inhibition and the reduced risk of COVID-19 hospitalization.Funding: Start-up Fund for high-level talents of Fujian Medical University.

Background—: Spousal caregivers of cancer patients suffer psychological and physical burdens that may affect their risk of subsequently developing coronary heart disease and stroke. Methods and Results—: Cancer patients were identified in the Swedish Cancer Registry, and information on their spouses was retrieved from the Swedish Multi-Generation Register. Follow-up of caregivers was performed from the date of the first diagnosis of cancer in their spouses through 2008. Standardized incidence ratios were calculated for spousal caregivers of cancer patients compared with those without an affected spouse. After the cancer diagnosis in wives, the risks of coronary heart disease, ischemic stroke, and hemorrhagic stroke in husbands were 1.13 (95% confidence interval [CI], 1.10–1.16), 1.24 (95% CI, 1.21–1.27), and 1.25 (95% CI, 1.18–1.32), respectively. The corresponding risks in wives with an affected husband were 1.13 (95% CI, 1.10–1.16), 1.29 (95% CI, 1.26–1.32), and 1.27 (95% CI, 1.19–1.34). The increases were consistent over time and were more pronounced if the spouse was affected by a cancer with a high mortality rate, such as pancreatic and lung cancers. Conclusions—: Spousal caregivers of cancer patients have increased risks of coronary heart disease and stroke that persist over time. Clinical attention should be paid to spousal caregivers, especially those caring for cancer patients with high mortality rates.

The risk of solid and hematological malignancy in patients with Turner syndrome, characterized by X chromosome monosomy in women, and Klinefelter syndrome, characterized with two and more X chromosomes in men, is not well established, but such evidence may have etiological implications on cancer development. We identified a total of 1,409 women with Turner syndrome and 1,085 men with Klinefelter syndrome from the Swedish Hospital Discharge and Outpatient Register. These individuals were further linked to the Swedish Cancer Register to examine the standardized incidence ratios (SIRs) of cancer using the general population without Turner and Klinefelter syndromes as reference. The overall risk of cancer was 1.34 for women with Turner syndrome; it was increased only for solid tumors. For a specific type of tumor, the risk of melanoma and central nervous system tumor was significantly increased. For persons with Klinefelter syndrome, the risk of solid tumors was decreased (SIR = 0.66), whereas the risk of hematological malignancy was increased (SIR = 2.72). Non‐Hodgkin lymphoma and leukemia showed an increased SIR of 3.02 and 3.62, respectively. Our study supported the hypothesis that X chromosome plays an important role in the etiology of solid tumors. The underlying mechanisms for the increased incidence of non‐Hodgkin lymphoma and leukemia in persons with Klinefelter syndrome need to be investigated further.

Significance: Classification of cancer provides crucial guidance for clinical treatment and mechanistic studies. Our work extends previous glioma classification studies in that we established EGFR module (EM)/ PDGFRA module (PM) glioma classification scheme based on gene coexpression modules around key signaling pathways conserved in neural development and gliomagenesis. We identified coexpressed EM and PM genes as classifiers. Based on the EM and PM signatures, our classification scheme robustly assigns adult low-grade and high-grade diffuse gliomas into three major subtypes that are distinct in patient survival, and in transcriptomic and genomic patterns. Our work suggests that EM and PM genes may play currently unrecognized roles in gliomagenesis. EM/PM glioma classification scheme forms a framework toward establishing molecular diagnostic tools and identifying new therapeutic targets to combat gliomas.

Registry‐based cancer incidence and mortality data are widely used for etiologic research, cancer control and health care monitoring and planning. The complete coverage of all cases is the key criteria of data quality but it is difficult to assess because the alternative sources of data may be flawed. The aim of our study was to examine, at a nationwide level, the completeness of the Swedish Cancer Registry (CR) regarding persons who died of cancer, based on the Cause of Death Registry (DR), and using the Hospital Discharge Registry (HDR) as an additional source of data. Individuals who died of cancer from years 1999 through 2008 recorded in DR were linked to CR and HDR. A total of 190,692 individuals were identified from DR with cancer as the underlying cause of death; the mean identification rate of concordant cancer in CR was 79.8%, depending on tumor site and age at death. Breast, bladder and prostate cancers showed the highest rate of identification, whereas bone, liver and pancreatic cancers showed the lowest rate of identification. CR had no records on 10.6% of cancer cases recorded in DR. Similarly, the identification rate in HDR was 84.5% for concordant cancer and with 9.6% of cases missing. Neither source reported cancers for 3.4% of cancer cases recorded in DR. In conclusion, some 10% of cancer deaths had no cancer records in CR or in HDR, and 3.4% were missing in both sources. The identification rate depended on tumor site, age at death and, to some extent, death outside hospital.

Hepatitis D virus (HDV) is dependent on the presence of hepatitis B virus (HBV) for transmission and replication because of its inability to produce its own coat. It remains unclear whether HDV infection increases the risk of hepatocellular carcinoma. Using the Swedish Hospital Discharge Register and Outpatient Registry, we identified 9160 patients with chronic HBV infection between 1997 and 2008, of whom 327 had chronic HDV infection and 323 had acute HDV infection. Standardized incidence ratios (SIRs) were calculated for these patients compared with the general population. The risk of hepatocellular carcinoma was greatly increased in patients with HBV and HDV (SIR = 137.17, 95% confidence interval [CI] = 62.19 to 261.51). The risk of hepatocellular carcinoma among patients with HBV and HDV was increased (SIR = 6.11, 95% CI = 2.77 to 11.65) when patients with chronic HBV infection alone were used as the reference population. Similar results were observed for patients with chronic HDV infection (SIR = 99.26, 95% CI = 42.39 to 196.55). Our findings indicate that HDV is a strong risk factor for hepatocellular carcinoma.