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Ruud Lensen,1 Mihai G Netea,2,3 Frits R Rosendaal4 1Cordaan Health Care Organization, Amsterdam, the Netherlands; 2Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands; 3Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany; 4Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the NetherlandsCorrespondence: Ruud LensenCordaan Health Care Organization, Amsterdam, the NetherlandsTel +31204356300Email ruudlensen@hotmail.comPurpose: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection impacted morbidity and mortality during the pandemic of 2020– 2021. A number of anti-COVID-19 vaccines have been developed with an unprecedented speed. While these vaccines have good efficacy and are safe, the experience with their use is limited and hence the knowledge of rare side effects. Identifying rare complications is important for future safe use of these vaccines.Materials and Methods: Here, we report a case of a 82-year old patient with dementia who was admitted to a nursing home in the Netherlands. After vaccination with COVID-19 vaccination, physical examinations and lab tests were performed.Results: She had a reactivation of hepatitis C infection after vaccination with the mRNA-based Pfizer–BioNTech COVID-19 vaccine. This reactivation manifested with jaundice, loss of consciousness, hepatic coma and death.Conclusion: This reactivation of hepatitis C virus after vaccination with the Pfizer–BioNTech COVID‑19 vaccine suggests a need for critical consideration of individuals with prior HCV infection and considered for COVID-19 vaccination.Keywords: SARS-CoV-2, hepatitis C, virus reactivation, COVID-19 vaccination

Fernanda A Orsi,1,2 Willem M Lijfering,2,3 Arnoud Van der Laarse,4,5 L Renee Ruhaak,4 Frits R Rosendaal,2 Suzanne C Cannegieter,2–3,6 Christa Cobbaert41Department of Clinical Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil; 2Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; 3Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; 4Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands; 5Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; 6Department of Internal Medicine, Section of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The NetherlandsPurpose: Apolipoproteins C-I, C-II, C-III and E have been associated with risk of arterial thrombotic diseases. We investigated whether these apolipoproteins have prothrombotic properties and are associated with risk of venous thromboembolism (VTE).Patients and methods: A total of 127 VTE patients and 299 controls were randomly selected from the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis study (1999–2004), in the Netherlands. The apolipoproteins were quantified using mass spectrometry (LC/MS/MS), and their levels were analyzed as continuous variable (per SD increase).Results: In controls, increases in levels of apolipoproteins were associated with increases in levels of vitamin K-dependent factors, factor XI, antithrombin and clot lysis time. Additionally, increasing apolipoproteins C-III and E levels were associated with higher factor VIII and von Willebrand factor levels. Levels of C-reactive protein were not associated with any apolipoprotein. The age- and sex-adjusted odds ratios of apolipoproteins E, C-III, CII and CI to the risk of venous thrombosis were 1.21 (95% CI, 0.98–1.49), 1.19 (95% CI, 0.99–1.44), 1.24 (95% CI, 0.95–1.61) and 1.06 (95% CI, 0.87–1.30) per SD increase, respectively. These odds ratios did not attenuate after adjustments for statin use, estrogen use, BMI, alcohol use, and self-reported diabetes.Conclusions: Levels of apolipoproteins C-I, C-II, C-III and E are associated with those of several coagulation factors. However, whether these apolipoproteins are also associated with an increased risk of VTE remains to be established.Keywords: thrombosis, proteomics, lipids, cholesterol, coagulation, risk factors

Hilde Jensvoll,1,2 Marianne T Severinsen,3,4 Jens Hammerstrøm,5 Sigrid K Brækkan,1,2 Søren R Kristensen,4,6 Suzanne C Cannegieter,7 Kristine Blix,1,2 Anne Tjønneland,8 Frits R Rosendaal,1,7,9 Olga Dziewiecka,1 Kim Overvad,10,11 Inger Anne Næss,12 John-Bjarne Hansen1,21Department of Clinical Medicine, KG Jebsen – Thrombosis Research and Expertise Center (TREC), UiT – The Arctic University of Norway, 2Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway; 3Department of Hematology, Aalborg University Hospital, 4Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 5Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; 6Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark; 7Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; 8Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark; 9Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands; 10Department of Cardiology, Aalborg University Hospital, Aalborg, 11Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark; 12Department of Hematology, Trondheim University Hospital, Trondheim, NorwayBackground: Although venous thromboembolism (VTE) is a known common complication in cancer patients, there is limited knowledge on patient-related and cancer-specific risk factors in the general population. The Scandinavian Thrombosis and Cancer (STAC) Cohort was established by merging individual data from three large Scandinavian cohorts (The Tromsø Study, the second Nord-Trøndelag Health Study, and the Danish Diet, Cancer and Health Study). Here, we present the profile of the STAC cohort and provide age-specific incidence rates of VTE and cancerMethods: The STAC cohort includes 144,952 subjects aged 19–101 years without previous VTE or cancer. Baseline information collected in 1993–1997 included physical examination, self-administered questionnaires, and blood samples. Validated VTE events and cancer diagnoses were registered up to 2007–2012.Results: There were 2,444 VTE events (1.4 per 1,000 person-years [PY]) during follow-up, and the incidence increased exponentially from 0.3 per 1,000 PY in subjects aged 20–29 years to 6.4 per 1,000 PY in subjects aged 80+. Overall, 51% of the VTE events were provoked, and cancer was the most common provoking factor (19%), followed by immobilization and surgery (both 15%). In total, 19,757 subjects developed cancer during follow-up (9.8 per 1,000 PY), and the 5-year age-specific incidence rates of cancer were coherent with corresponding rates from the Norwegian Cancer Registry.Conclusion: The STAC cohort will provide a unique opportunity to explore the epidemiology and impact of genetic and environmental patient-related and cancer-specific risk factors for VTE in the general population.Keywords: venous thromboembolism, incidence rates, person-years, pulmonary embolism, population-based cohort, prospective, cancer

To investigate the determinants of hand strength in patients with hand osteoarthritis (OA). Pinch and cylinder grip strength were measured in 527 patients with hand OA diagnosed by their treating rheumatologist from the Hand OSTeoArthritis in Secondary care (HOSTAS) study. Radiographs of hands (22 joints) were scored 0–3 (scaphotrapeziotrapezoid and first interphalangeal joints 0–1) on osteophytes and joint space narrowing following the Osteoarthritis Research Society International atlas. The first carpometacarpal joint (CMC1) was scored 0–1 for subluxation. Pain was assessed with the Australian/Canadian Hand Osteoarthritis Index pain subscale, and health-related quality of life with the Short Form-36. Regression analysis served to investigate associations of hand strength with patient, disease, and radiographic features. Hand strength was negatively associated with female sex, age, and pain. Reduced hand strength was associated with reduced quality of life, although less after adjusting for pain. Radiographic features of hand OA were associated with reduced grip strength when solely adjusted for sex and body mass index, but only CMC1 subluxation in the dominant hand remained significantly associated with pinch grip adjusted additionally for age (−0.511 kg, 95% confidence interval −0.975; −0.046). Mediation analysis showed low and not significant percentages of mediation of hand OA in the association between age and grip strength. Subluxation of CMC1 is associated with reduced grip strength, whereas associations with other radiographic features seem to be confounded by age. In the relationship between age and hand strength, radiographic hand OA severity is not an important mediator. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the nature and extent of aesthetic dissatisfaction in patients with hand osteoarthritis (OA), and to investigate its impact on daily life and its determinants.Method: Patients with primary hand OA, consulting secondary care, underwent physical examination for the number of joints with bony joint enlargements, soft tissue swelling and deformities, and radiographs. Questionnaires were filled in to measure pain and function (Functional Index for Hand Osteoarthritis, FIHOA), dissatisfaction with the appearance of the hands and its impact (aesthetic scales from the Michigan Hand Outcomes Questionnaire, MHQ), anxiety and depression (the Hospital Anxiety and Depression Scale, HADS), and illness perceptions (the revised Illness Perception Questionnaire, IPQ-R). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using multivariate logistic regression as measures of relative risk for dissatisfaction with appearance or its impact, adjusted for age, sex, body mass index (BMI), and joint-specific abnormalities (bony joint enlargements, deformities, or radiographic severity), self-reported pain and function.Results: Of 247 patients (mean age 61.6 years, 88% women), 63 (26%) were aesthetically dissatisfied and 33 (13%) reported impact on daily life due to dissatisfaction. Patients with joint-specific abnormalities were at higher risk for reporting dissatisfaction. Patients who reported impact also reported more depression and negative illness perceptions, independently from joint-specific abnormalities.Conclusions: Hand OA patients report aesthetic dissatisfaction with their hands regularly, especially in those with joint abnormalities. This dissatisfaction has a negative impact in a small group of patients who also reported more depression and negative illness perceptions. These results indicate the influence of psychosocial factors on outcome measures in patients with hand OA. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether all-cause mortality and deaths due to cardiovascular disease are increased in patients who have consulted primary or secondary health care with symptoms and signs of osteoarthritis (OA). Method: This study included 383 patients with symptomatic OA at multiple sites from the Genetics ARthrosis and Progression (GARP) study (mean age 60 years, 82% women, 3693 person-years of follow-up) and 459 patients with primary hand, knee, or hip OA from the Osteoarthritis Care Clinic (OCC) study (mean age 61 years, 88% women, 1890 person-years of follow-up). Standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) were calculated for all-cause mortality and causes of deaths in comparison to the general population. Cox proportional hazard ratios (HRs) with 95% CIs were used to associate baseline characteristics with all-cause mortality. Results: In the GARP study, 26 patients died whereas 48 deaths were expected (SMR 0.54, 95% CI 0.37-0.79). The SMR was 0.47 (95% CI 0.29-0.76) in women and 0.73 (95% CI 0.39-1.35) in men. Similar results were found in the OCC study (SMR 0.45, 95% CI 0.25-0.82). Malignancy and cardiovascular disease were the main causes of deaths in GARP. Male sex (HR 3.04, 95% CI 1.38-6.69), increasing age (HR 1.10, 95% CI 1.05-1.16), and self-reported cancer (HR 8.29, 95% CI 3.12-22.03) were associated with increased mortality in GARP. Conclusions: Patients consulting health care for their OA are not at higher risk of death than the general population. These results suggest that the management of OA patients may not need to focus specifically on the treatment of cardiovascular risk factors and comorbidities. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In a sibpair study of osteoarthritis (OA) patients, we investigated whether, upon stimulation with lipopolysaccharide (LPS), variations in the innate ex vivo production of interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), IL-10, and tumor necrosis factor alpha (TNFalpha) in whole-blood assays contribute to the risk of OA. METHODS: Data from 305 patients with OA at multiple sites (hand, knee, hip, and spine), whose median age was 60 years (range 43-79 years), were compared with those from 137 controls. OA was defined in accordance with the American College of Rheumatology criteria. Whole-blood samples were stimulated with LPS (10 ng/ml). In the supernatants, cytokines were measured by enzyme-linked immunosorbent assay. Odds ratios (ORs) were used as measures of the relative risk of OA in relation to quartiles of IL-1beta, IL-1Ra, TNFalpha, and IL-10 production. The ORs were adjusted for sex and age, and 95% confidence intervals (95% CIs) were computed using robust standard errors to take into account the intrafamily effect. RESULTS: Subjects in the highest quartile of IL-1beta and IL-1Ra had an increased risk of OA (OR 3.3, 95% CI 1.4-7.9 and OR 8.0, 95% CI 3.7-17.4, respectively), while subjects in the lowest quartile of IL-10 had a 3-fold increased risk of OA (OR 3.1, 95% CI 1.5-6.5). High innate ex vivo production of TNFalpha was not associated with an increased risk of OA. CONCLUSION: Subjects with a high innate ex vivo production of IL-1beta and IL-1Ra and low innate ex vivo production of IL-10 have an increased risk of OA. These results suggest that a proportion of the genetic susceptibility to OA may be encoded for by variations in innate cytokine activity. [ABSTRACT FROM AUTHOR]

Context: A genetic variant in alpha-adducin has been associated with renal sodium reabsorption and salt-sensitive hypertension. Whether this genetic variant modifies the effect of diuretic therapy on the incidence of myocardial infarction (MI) and stroke is unknown.Objectives: To estimate the interaction between alpha-adducin and diuretic therapy on the risk of MI or stroke. Specifically, we hypothesized that in participants with treated hypertension, the risk of MI or stroke associated with diuretic use would be lower in carriers of the adducin variant than in carriers of the adducin wild-type genotype.Design, Setting, and Participants: Population-based case-control study of patients enrolled in a health maintenance organization, treated pharmacologically for hypertension, and genotyped as homozygous carriers of the adducin wild-type genotype or carriers of 1 or 2 copies of the Trp460 variant allele. Cases had a first nonfatal MI (n = 206) or stroke (n = 117) between January 1995 and December 1998. Controls (n = 715) were a stratified random sample of pharmacologically treated hypertensive patients who were matched to MI cases by age, sex, and calendar year.Main Outcome Measure: Risk of the combined outcome of first nonfatal MI or stroke.Results: The adducin variant was present in more than one third of the participants. Among the 653 carriers of the adducin wild-type genotype, diuretic therapy was not associated with the risk of MI or stroke (odds ratio [OR], 1.09; 95% confidence interval [CI], 0.78-1.52). Among the 385 carriers of the adducin variant allele, diuretic therapy was associated with a lower risk of the combined outcome of MI and stroke than other antihypertensive therapies (OR, 0.49; 95% CI, 0.32-0.77). The OR in carriers of the adducin variant was less than half of the OR in carriers of the wild-type genotype (P =.005). The case-control synergy index (SI) was 0.45 (95% CI, 0.26-0.79) for the combined outcome of MI and stroke. The point estimates of the diuretic-adducin interaction were similar in separate analyses of MI (SI, 0.41; 95% CI, 0.21-0.80) and stroke (SI, 0.53; 95% CI, 0.24-1.19). The diuretic-adducin interaction was not confounded by traditional cardiovascular risk factors, was specific to diuretic therapy but not present for other major antihypertensive drug classes, and did not differ substantially between subgroups defined by age, sex, race, diabetes, and history of cardiovascular disease.Conclusions: In carriers of the adducin variant, diuretic therapy was associated with a lower risk of combined MI or stroke than other antihypertensive therapies. If these findings are confirmed in other studies, this large subgroup of the hypertensive population may be especially likely to benefit from low-dose diuretic therapy. [ABSTRACT FROM AUTHOR]