Long-term risk of neoplastic events after childhood growth hormone treatment: a population-based cohort study in Sweden.

Background: Increased risk of neoplastic events after recombinant human growth hormone (rhGH) treatment in childhood has been an ongoing concern but long-term safety data are limited. Methods: A nationwide population-based cohort study in Sweden of patients treated with rhGH during childhood between 1985-2010, due to isolated growth hormone deficiency (GHD), small for gestational age (SGA) and idiopathic short stature (ISS). The comparison group consisted of 15 age-, sex-, and region-matched controls per patient, randomly selected from the general population. Data on neoplastic events and covariates, such as gestational age, birth weight, birth length, socioeconomic status, and height at study start, were collected through linkage with population-based registers. The cohort was followed for neoplastic events until the end of 2020. Results: 53,444 individuals (3,408 patients; 50,036 controls) were followed for up to 35 years, with a median follow-up of 19.8 years and a total of 1,050,977 person-years. Patients showed a moderately increased hazard ratio (HR) for neoplastic events overall compared to controls (HR 1.28, 95% CI: 1.12-1.46), but only significant for males (HR 1.39, 95% CI: 1.17-1.66) and not females (HR 1.15, 95% CI: 0.94-1.41). Longer treatment duration was associated with an increased HR, but no association was found between neoplastic events and mean or cumulative dose. No increased risk of malignant neoplasms was observed for the patients compared to matched controls (HR 0.91 95% CI: 0.66-1.26). Conclusion: No association was found between rhGH treatment during childhood for GHD, SGA, or ISS and malignant neoplastic events in early to mid-adulthood. A moderate increase in overall neoplastic events was observed due to an increased number of events in male patients.

Performance of the 2017 EULAR/ACR Classification Criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups: a scoping review.

The 2017 EULAR/ACR classification criteria for adult/juvenile idiopathic inflammatory myopathies (IIM) were established using a data-driven approach by an international group of myositis experts to allow classification of IIM and its major subtypes. Since their publication, the performance of the criteria has been tested in multiple cohorts worldwide and significant limitations have been identified. Moreover, the understanding and classification of IIM have evolved since 2017. This scoping review was undertaken as part of a large international project to revise the EULAR/ACR criteria and aims to i) summarise the evidence from the current literature on the performance characteristics of the 2017 EULAR/ACR classification criteria in various cohorts and IIM subtypes, and ii) delineate the factors that need to be considered in the revision of the classification criteria. A systematic search of Medline (via PubMed), Cumulative Index to Nursing and Allied Health Literature, and conference abstract archives was conducted independently by three investigators for studies on the EULAR/ACR criteria published between October 2017 and January 2023. This scoping review of 19 articles and 13 abstracts revealed overall good performance characteristics of the EULAR/ACR criteria for IIM, yet deficiencies in lack of inclusion of certain IIM subtypes, such as immune mediated necrotising myopathy, amyopathic dermatomyositis, antisynthetase syndrome and overlap myositis. Published modifications that may improve the performance characteristics of the criteria for classification of IIM subtypes were also summarised. The results of this review suggest that a revision of the EULAR/ACR criteria is warranted.

Risk of Venous Thromboembolic Events After Surgery for Cancer.

Importance: The risks and benefits of thromboprophylaxis therapy after cancer surgery are debated. Studies that determine thrombosis risk after cancer surgery with high accuracy are needed. Objectives: To evaluate 1-year risk of venous thromboembolic events after major cancer surgery and how these events vary over time. Design, Setting, and Participants: This register-based retrospective observational matched cohort study included data on the full population of Sweden between 1998 and 2016. All patients who underwent major surgery for cancer of the bladder, breast, colon or rectum, gynecologic organs, kidney and upper urothelial tract, lung, prostate, or gastroesophageal tract were matched in a 1:10 ratio with cancer-free members of the general population on year of birth, sex, and county of residence. Data were analyzed from February 13 to December 5, 2023. Exposure: Major surgery for cancer. Main Outcomes and Measures: The main outcome was incidence of venous thromboembolic events within 1 year after the surgery. Crude absolute risks and risk differences of events within 1 year and adjusted time-dependent cause-specific hazard ratios (HRs) of postdischarge events were calculated. Results: A total of 432 218 patients with cancer (median age, 67 years [IQR, 58-75 years]; 68.7% women) and 4 009 343 cancer-free comparators (median age, 66 years [IQR, 57-74 years]; 69.3% women) were included in the study. The crude 1-year cumulative risk of pulmonary embolism was higher among the cancer surgery population for all cancers, with the following absolute risk differences: for bladder cancer, 2.69 percentage points (95% CI, 2.33-3.05 percentage points); for breast cancer, 0.59 percentage points (95% CI 0.55-0.63 percentage points); for colorectal cancer, 1.57 percentage points (95% CI, 1.50-1.65 percentage points); for gynecologic organ cancer, 1.32 percentage points (95% CI, 1.22-1.41 percentage points); for kidney and upper urinary tract cancer, 1.38 percentage points (95% CI, 1.21-1.55 percentage points); for lung cancer, 2.61 percentage points (95% CI, 2.34-2.89 percentage points); for gastroesophageal cancer, 2.13 percentage points (95% CI, 1.89-2.38 percentage points); and for prostate cancer, 0.57 percentage points (95% CI, 0.49-0.66 percentage points). The cause-specific HR of pulmonary embolism comparing patients who underwent cancer surgery with matched comparators peaked just after discharge and generally plateaued 60 to 90 days later. At 30 days after surgery, the HR was 10 to 30 times higher than in the comparison cohort for all cancers except breast cancer (colorectal cancer: HR, 9.18 [95% CI, 8.03-10.50]; lung cancer: HR, 25.66 [95% CI, 17.41-37.84]; breast cancer: HR, 5.18 [95% CI, 4.45-6.05]). The hazards subsided but never reached the level of the comparison cohort except for prostate cancer. Similar results were observed for deep vein thrombosis. Conclusions and Relevance: This cohort study found an increased rate of venous thromboembolism associated with cancer surgery. The risk persisted for about 2 to 4 months postoperatively but varied between cancer types. The increased rate is likely explained by the underlying cancer disease and adjuvant treatments. The results highlight the need for individualized venous thromboembolism risk evaluation and prophylaxis regimens for patients undergoing different surgery for different cancers.

Risk of Postoperative Ischemic Stroke and Myocardial Infarction in Patients Operated for Cancer.

BACKGROUND: Risk assessment for ischemic stroke (IS) and myocardial infarction (MI) is done routinely before surgery, but the increase in risks associated with surgery is not known. The aim of this study is to assess the risk of arterial ischemic events during the first year after oncological surgery. METHODS: We used Swedish healthcare databases to identify 443,300 patients who underwent cancer surgery between 1987 and 2016 and 4,127,761 matched comparison subjects. We estimated odds ratios (ORs) for myocardial infarction and ischemic stroke during the hospitalization with logistic regression and calculated 1-year cumulative incidences and hazard ratios (HRs) with 95% confidence intervals (CIs) for the outcomes after discharge. RESULTS: The cumulative incidences of myocardial infarction and ischemic stroke during the first postoperative year were 1.33% and 1.25%, respectively. In the comparison cohort, the corresponding 1-year cumulative incidences were 1.04% and 1.00%. During the hospitalization, the OR for myocardial infarction was 8.81 (95% CI 8.24-9.42) and the OR for ischemic stroke was 6.71 (95% CI 6.22-7.23). After discharge, the average HR during follow-up for 365 days was 0.90 (95% CI 0.87-0.93) for myocardial infarction and 1.02 (95% CI 0.99-1.05) for ischemic stroke. CONCLUSIONS: We found an overall increased risk of IS and MI during the first year after cancer surgery that was attributable to events occurring during the hospitalization period. After discharge from the hospital, the overall risk of myocardial infarction was lower among the cancer surgery patients than among matched comparison subjects.

Multisite assessment of reproducibility in high-content cell migration imaging data.

High-content image-based cell phenotyping provides fundamental insights into a broad variety of life science disciplines. Striving for accurate conclusions and meaningful impact demands high reproducibility standards, with particular relevance for high-quality open-access data sharing and meta-analysis. However, the sources and degree of biological and technical variability, and thus the reproducibility and usefulness of meta-analysis of results from live-cell microscopy, have not been systematically investigated. Here, using high-content data describing features of cell migration and morphology, we determine the sources of variability across different scales, including between laboratories, persons, experiments, technical repeats, cells, and time points. Significant technical variability occurred between laboratories and, to lesser extent, between persons, providing low value to direct meta-analysis on the data from different laboratories. However, batch effect removal markedly improved the possibility to combine image-based datasets of perturbation experiments. Thus, reproducible quantitative high-content cell image analysis of perturbation effects and meta-analysis depend on standardized procedures combined with batch correction.

Prediction of conditional survival in esophageal cancer in a population-based cohort study.

BACKGROUND: The authors aimed to produce a prediction model for survival at any given date after surgery for esophageal cancer (conditional survival), which has not been done previously. MATERIALS AND METHODS: Using joint density functions, the authors developed and validated a prediction model for all-cause and disease-specific mortality after surgery with esophagectomy, for esophageal cancer, conditional on postsurgery survival time. The model performance was assessed by the area under the receiver operating characteristic curve (AUC) and risk calibration, with internal cross-validation. The derivation cohort was a nationwide Swedish population-based cohort of 1027 patients treated in 1987-2010, with follow-up throughout 2016. This validation cohort was another Swedish population-based cohort of 558 patients treated in 2011-2013, with follow-up throughout 2018. RESULTS: The model predictors were age, sex, education, tumor histology, chemo(radio)therapy, tumor stage, resection margin status, and reoperation. The medians of AUC after internal cross-validation in the derivation cohort were 0.74 (95% CI: 0.69-0.78) for 3-year all-cause mortality, 0.76 (95% CI: 0.72-0.79) for 5-year all-cause mortality, 0.74 (95% CI: 0.70-0.78) for 3-year disease-specific mortality, and 0.75 (95% CI: 0.72-0.79) for 5-year disease-specific mortality. The corresponding AUC values in the validation cohort ranged from 0.71 to 0.73. The model showed good agreement between observed and predicted risks. Complete results for conditional survival any given date between 1 and 5 years of surgery are available from an interactive web-tool: https://sites.google.com/view/pcsec/home . CONCLUSION: This novel prediction model provided accurate estimates of conditional survival any time after esophageal cancer surgery. The web-tool may help guide postoperative treatment and follow-up.

A prognostic model for predicting the duration of 20,049 sickness absence spells due to shoulder lesions in a population-based cohort in Sweden.

MAIN OBJECTIVE: Sickness absence duration for shoulder lesion patients is difficult to prognosticate, and scientific evidence for the sick-listing practice is lacking. Our objective was to develop a clinically implementable prediction model for the duration of a sickness absence spell due to shoulder lesions. METHODS: All new sickness absence spells due to shoulder lesions (ICD-10-code: M75) issued in the period January 2010-June 2012 that were longer than 14 days were identified through the nationwide sickness absence insurance register. Information on predictors was linked from four other nationwide registers. Piecewise-constant hazards regression models were fitted to predict duration of sickness absence. The model was developed and validated using split sample validation. Variable selection was based on log-likelihood loss ranking when excluding a variable from the model. The model was evaluated using calibration plots and the c-statistic. RESULTS: 20 049 sickness absence spells were identified, of which 34% lasted >90 days. Predictors included in the model were age, sex, geographical region, occupational status, educational level, birth country, specialized healthcare at start of the spell, number of sickness absence days in the last 12 months, and specialized healthcare the last 12 months, before start date of the index sickness absence spell. The model was satisfactorily specified and calibrated. Overall c-statistic was 0.54 (95% CI 0.53-0.55). C-statistic for predicting durations >90, >180, and >365 days was 0.61, 0.66, and 0.74, respectively. SIGNIFICANCE: The model can be used to predict the duration of sickness absence due to shoulder lesions. Covariates had limited predictive power but could discriminate the very long sickness absence spells from the rest.

Alcohol as a risk factor for mortality in liver transplant patients in Sweden.

OBJECTIVES: Liver transplantation (LT) is the only available cure for end-stage liver disease and one of the best treatment options for hepatocellular carcinomas (HCC). Patients with known alcohol-associated cirrhosis (AC) are routinely assessed for alcohol dependence or abuse before LT. Patients with other liver diseases than AC may consume alcohol both before and after LT. The aim of this study was to assess the effects of alcohol drinking before and after LT on patient and graft survival regardless of the etiology of liver disease. MATERIALS AND METHODS: Between April 2012 and December 2015, 200 LT-recipients were interviewed using the Lifetime Drinking History and the Addiction Severity Index questionnaire. Patients were categorized as having AC, n = 24, HCC and/or hepatitis C cirrhosis (HCV), n = 69 or other liver diseases, n = 107. Patients were monitored and interviewed by transplantation-independent staff for two years after LT with questions regarding their alcohol consumption. Patient and graft survival data were retrieved in October 2019. RESULTS: Patients with AC had an increased hazard ratio (HR) for death after LT (crude HR: 4.05, 95% CI: 1.07-15.33, p = 0.04) and for graft loss adjusted for age and gender (adjusted HR: 3.24, 95% CI 1.08-9.77, p = 0.04) compared to the other patients in the cohort. There was no significant effect of the volume of alcohol consumed before or after LT on graft loss or overall survival. CONCLUSION: Patients transplanted for AC have a worse prognosis, but we found no correlation between alcohol consumed before or after LT and graft or patient survival.

Modeling sign concordance of quantile regression residuals with multiple outcomes.

Quantile regression permits describing how quantiles of a scalar response variable depend on a set of predictors. Because a unique definition of multivariate quantiles is lacking, extending quantile regression to multivariate responses is somewhat complicated. In this paper, we describe a simple approach based on a two-step procedure: in the first step, quantile regression is applied to each response separately; in the second step, the joint distribution of the signs of the residuals is modeled through multinomial regression. The described approach does not require a multidimensional definition of quantiles, and can be used to capture important features of a multivariate response and assess the effects of covariates on the correlation structure. We apply the proposed method to analyze two different datasets.

Plasticity of Individual Lung Function States from Childhood to Adulthood.

Rationale: Recent evidence highlights the importance of optimal lung development during childhood for health throughout life. Objectives: To explore the plasticity of individual lung function states during childhood. Methods: Prebronchodilator FEV1 z-scores determined at age 8, 16, and 24 years in the Swedish population-based birth cohort BAMSE (Swedish abbreviation for Child [Barn], Allergy, Milieu, Stockholm, Epidemiological study) (N = 3,069) were used. An unbiased, data-driven dependent mixture model was applied to explore lung function states and individual state chains. Lung function catch-up was defined as participants moving from low or very low states to normal or high or very high states, and growth failure as moving from normal or high or very high states to low or very low states. At 24 years, we compared respiratory symptoms, small airway function (multiple-breath washout), and circulating inflammatory protein levels, by using proteomics, across states. Models were replicated in the independent Dutch population-based PIAMA (Prevention and Incidence of Asthma and Mite Allergy) cohort. Measurements and Main Results: Five lung function states were identified in BAMSE. Lung function catch-up and growth failure were observed in 74 (14.5%) BAMSE participants with low or very low states and 36 (2.4%) participants with normal or high or very high states, respectively. The occurrence of catch-up and growth failure was replicated in PIAMA. Early-life risk factors were cumulatively associated with the very low state, as well as with catch-up (inverse association) and growth failure. The very low state as well as growth failure were associated with respiratory symptoms, airflow limitation, and small airway dysfunction at adulthood. Proteomics identified IL-6 and CXCL10 (C-X-C motif chemokine 10) as potential biomarkers of impaired lung function development. Conclusions: Individual lung function states during childhood are plastic, including catch-up and growth failure.

Improved prediction of 10-year risk of severe liver disease in the general population using commonly available biomarkers.

BACKGROUND: Estimating the risk for cirrhosis in the general population is complex. Existing prediction tools are in general unsatisfactory. AIMS: To explore if using commonly available biomarkers can improve the commonly used FIB-4 score in the identification of subgroups at risk of cirrhosis. METHODS: We used laboratory and clinical data on 126,925 individuals aged 35-79 years in Stockholm, Sweden, undergoing health examinations from 1985 to 1996. We used Swedish nationwide registries to ascertain 10-year cumulative incidence of severe liver disease, a composite of diagnoses corresponding to cirrhosis and its complications. We considered combinations of biomarkers associated with severe liver disease to identify subgroups with different risk profiles. RESULTS: During an average follow-up of 9.3 years, we ascertained 630 incident cases of severe liver disease (0.5%). Age, the FIB-4 score, diabetes or impaired glucose and gamma-glutamyl transferase (gGT) were the most relevant characteristics for classifying risk profiles. Using these factors, we identified 24 groups with a cumulative incidence of severe liver disease at 10 years ranging from 0.2% (age 35-65, low FIB-4, no diabetes or impaired glucose and normal gGT) to 32.1% (age 35-65, high FIB-4, diabetes or impaired glucose and high gGT). CONCLUSIONS: Identification of subjects at increased risk of severe liver disease in the general population using the FIB-4 score can be substantially improved by adding age and specific biomarkers commonly available in the primary care setting. These parameters should be considered for inclusion in the development of future risk prediction models.

Ambient air pollution and inflammation-related proteins during early childhood.

BACKGROUND AND AIM: Experimental studies show that short-term exposure to air pollution may alter cytokine concentrations. There is, however, a lack of epidemiological studies evaluating the association between long-term air pollution exposure and inflammation-related proteins in young children. Our objective was to examine whether air pollution exposure is associated with inflammation-related proteins during the first 2 years of life. METHODS: In a pooled analysis of two birth cohorts from Stockholm County (n = 158), plasma levels of 92 systemic inflammation-related proteins were measured by Olink Proseek Multiplex Inflammation panel at 6 months, 1 year and 2 years of age. Time-weighted average exposure to particles with an aerodynamic diameter of <10 µm (PM10), <2.5 µm (PM2.5), and nitrogen dioxide (NO2) at residential addresses from birth and onwards was estimated via validated dispersion models. Stratified by sex, longitudinal cross-referenced mixed effect models were applied to estimate the overall effect of preceding air pollution exposure on combined protein levels, "inflammatory proteome", over the first 2 years of life, followed by cross-sectional protein-specific bootstrapped quantile regression analysis. RESULTS: We identified significant longitudinal associations of inflammatory proteome during the first 2 years of life with preceding PM2.5 exposure, while consistent associations with PM10 and NO2 across ages were only observed among girls. Subsequent protein-specific analyses revealed significant associations of PM10 exposure with an increase in IFN-gamma and IL-12B in boys, and a decrease in IL-8 in girls at different percentiles of proteins levels, at age 6 months. Several inflammation-related proteins were also significantly associated with preceding PM10, PM2.5 and NO2 exposures, at ages 1 and 2 years, in a sex-specific manner. CONCLUSIONS: Ambient air pollution exposure influences inflammation-related protein levels already during early childhood. Our results also suggest age- and sex-specific differences in the impact of air pollution on children's inflammatory profiles.

Therapist-Supported Internet-Delivered Exposure and Response Prevention for Children and Adolescents With Tourette Syndrome: A Randomized Clinical Trial.

Importance: The availability of behavior therapy for individuals with Tourette syndrome (TS) and chronic tic disorder (CTD) is limited. Objective: To determine the efficacy and cost-effectiveness of internet-delivered exposure and response prevention (ERP) for children and adolescents with TS or CTD. Design, Setting, and Participants: This single-masked, parallel group, superiority randomized clinical trial with nationwide recruitment was conducted at a research clinic in Stockholm, Sweden. Out of 615 individuals assessed for eligibility, 221 participants meeting diagnostic criteria for TS or CTD and aged 9 to 17 years were included in the study. Enrollment began in April 2019 and ended in April 2021. Data were analyzed between October 2021 and March 2022. Interventions: Participants were randomized to 10 weeks of therapist-supported internet-delivered ERP for tics (111 participants) or to therapist-supported internet-delivered education for tics (comparator group, 110 participants). Main Outcomes and Measures: The primary outcome was change in tic severity from baseline to the 3-month follow-up as measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS). YGTSS-TTSS assessors were masked to treatment allocation. Treatment response was operationalized as a score of 1 ("Very much improved") or 2 ("Much improved") on the Clinical Global Impression-Improvement scale. Results: Data loss was minimal, with 216 of 221 participants (97.7%) providing primary outcome data. Among randomized participants (152 [68.8%] boys; mean [SD] age, 12.1 [2.3] years), tic severity improved significantly, with a mean reduction of 6.08 points on the YGTSS-TTSS in the ERP group (mean [SD] at baseline, 22.25 [5.60]; at 3-month follow-up, 16.17 [6.82]) and 5.29 in the comparator (mean [SD] at baseline, 23.01 [5.92]; at 3-month follow-up, 17.72 [7.11]). Intention-to-treat analyses showed that the 2 groups improved similarly over time (interaction effect, -0.53; 95% CI, -1.28 to 0.22; P = .17). Significantly more participants were classified as treatment responders in the ERP group (51 of 108 [47.2%]) than in the comparator group (31 of 108 [28.7%]) at the 3-month follow-up (odds ratio, 2.22; 95% CI, 1.27 to 3.90). ERP resulted in more treatment responders at little additional cost compared with structured education. The incremental cost per quality-adjusted life-year gained was below the Swedish willingness-to-pay threshold, at which ERP had a 66% to 76% probability of being cost-effective. Conclusions and Relevance: Both interventions were associated with clinically meaningful improvements in tic severity, but ERP led to higher response rates at little additional cost. Trial Registration: ClinicalTrials.gov identifier: NCT03916055.

Characteristics of Patients in SPCG-15-A Randomized Trial Comparing Radical Prostatectomy with Primary Radiotherapy plus Androgen Deprivation Therapy in Men with Locally Advanced Prostate Cancer.

Background: There is no high-grade evidence for surgery as primary treatment for locally advanced prostate cancer. The SPCG-15 study is the first randomized trial comparing surgical treatment with radiotherapy. Objective: To describe the baseline characteristics of the first 600 randomized men in the SPCG-15 study. The study will compare mortality and functional outcomes. Design setting and participants: This study is a Scandinavian prospective, open, multicenter phase III randomized clinical trial aiming to randomize 1200 men. Intervention: Radical prostatectomy with or without consecutive radiotherapy (experimental) and radiotherapy with neoadjuvant androgen deprivation therapy (standard of care). Outcome measurements and statistical analysis: Cause-specific survival, metastasis-free survival, overall survival, and patient-reported bowel function, sexual health, and lower urinary tract symptoms were measured. Results and limitations: The distribution of characteristics was similar in the two study arms. The median age was 67 yr (range 45-75 yr). Among the operated men, 36% had pT3a stage of disease and 39% had pT3b stage. International Society of Urological Pathology grades 2, 3, 4, and 5 were prevalent in 21%, 35%, 7%, and 27%, respectively. Half of the men (51%) in the surgery arm had no positive lymph nodes. The main limitation is the pragmatic design comparing the best available practice at each study site leading to heterogeneity of treatment regimens within the study arms. Conclusions: We have proved that randomization between surgery and radiotherapy for locally advanced prostate cancer is feasible. The characteristics of the study population demonstrate a high prevalence of advanced disease, well-balanced comparison groups, and a demography mirroring the Scandinavian population of men with prostate cancer at large. Patient summary: This study, which has recruited >600 men, compares radiotherapy with surgery for prostate cancer, and an analysis at the time of randomization indicates that the study will be informative and generalizable to most men with locally advanced but not metastasized prostate cancer.

Quantile Differences in the Age-Related Decline in Cardiorespiratory Fitness Between Sexes in Adults Without Type 2 Diabetes Mellitus in the United States.

Objective: To comprehensively assess the extent to which the decline in cardiorespiratory fitness (CRF) with age differs between sexes. Participants and Methods: This study used data from the Aerobics Center Longitudinal Study, conducted between September 1974 and August 2006, consisting primarily of White adults from middle-to-upper socioeconomic strata restricted to adults without type 2 diabetes mellitus (33,742 men and 9,415 women). Quantile regression models were used to estimate the differences in age-associated changes in CRF between the sexes, estimated using a maximal treadmill test. Results: For adults aged up to 45 years, significant differences in slopes relating to age and CRF between men and women were observed for all adjusted percentiles of CRF other than the 90th percentile; women reported significantly greater declines in CRF per year. For those aged 45-60 years and those older than 60 years, no significant differences in age-related declines in CRF were observed between the sexes. Conclusion: This study found that compared with men, the onset of decline in CRF was found to occur earlier and at lower CRF percentiles in women. This is of particular concern, given that compared with men, women already tend to have lower CRF levels. These findings suggest that maintaining the levels of physical activity sufficient to maintain moderate-to-high levels of fitness is particularly important for women earlier during adulthood.

Hypercoagulation Detected by Rotational Thromboelastometry Predicts Mortality in COVID-19: A Risk Model Based on a Prospective Observational Study.

Background Severe disease due to the novel coronavirus disease 2019 (COVID-19) has been shown to be associated with hypercoagulation. The aim of this study was to assess the Rotational Thromboelastometry (ROTEM) as a marker of coagulopathy in hospitalized COVID-19 patients. Methods This was a prospective, observational study where patients hospitalized due to a COVID-19 infection were eligible for inclusion. Conventional coagulation tests and ROTEM were taken after hospital admission, and patients were followed for 30 days. A prediction model, including variables ROTEM EXTEM-MCF (Maximum Clot Firmness) which in previous data has been suggested a suitable marker of hypercoagulation, age, and respiratory frequency, was developed using logistic regression to evaluate the probability of death. Results Out of the 141 patients included, 18 (13%) died within 30 days. In the final prediction model, the risk of death within 30 days for a patient hospitalized due to COVID-19 was increased with increased EXTEM-MCF, age, and respiratory frequency. Longitudinal ROTEM data in the severely ill subpopulation showed enhanced hypercoagulation. In an in vitro analysis, no heparin effect on EXTEM-coagulation time (CT) was observed, supporting a severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) effect on prolonged initiation of coagulation. Conclusion Here, we show that hypercoagulation measured with ROTEM predicts 30-day mortality in COVID-19. Longitudinal ROTEM data strengthen the hypothesis of hypercoagulation as a driver of severe disease in COVID-19. Thus, ROTEM may be a useful tool to assess disease severity in COVID-19 and could potentially guide anticoagulation therapy.