We aimed to evaluate the performance of the Khorana score in predicting venous thromboembolic events in ambulatory cancer patients. Embase and MEDLINE were searched from January 2008 to June 2018 for studies which evaluated the Khorana score. Two authors independently screened studies for eligibility, extracted data, and assessed risk of bias. Additional data on the 6-month incidence of venous thromboembolism were sought by contacting corresponding authors. The incidence in each Khorana score risk group was estimated with random effects meta-analysis. A total of 45 articles and eight abstracts were included, comprising 55 cohorts enrolling 34,555 ambulatory cancer patients. For 27,849 patients (81%), 6-month follow-up data were obtained. Overall, 19% of patients had a Khorana score of 0 points, 64% a score of 1 or 2 points, and 17% a score of 3 or more points. The incidence of venous thromboembolism in the first six months was 5.0% (95%CI: 3.9-6.5) in patients with a low-risk Khorana score (0 points), 6.6% (95%CI: 5.6-7.7) in those with an intermediate-risk Khorana score (1 or 2 points), and 11.0% (95%CI: 8.8-13.8) in those with a high-risk Khorana score (3 points or higher). Of the patients with venous thromboembolism in the first six months, 23.4% (95%CI: 18.4-29.4) had been classified as high risk according to the Khorana score. In conclusion, the Khorana score can be used to select ambulatory cancer patients at high risk of venous thromboembolism for thromboprophylaxis; however, most events occur outside this high-risk group.

Background: The incidence of acute complications and mortality associated with COVID-19 remains poorly characterized. The aims of this systematic review and meta-analysis were to summarize the evidence on clinically relevant outcomes in hospitalized patients with COVID-19. Methods: MEDLINE, EMBASE, PubMed, and medRxiv were searched up to April 20, 2020, for studies including hospitalized symptomatic adult patients with laboratory-confirmed COVID-19. The primary outcomes were all-cause mortality and acute respiratory distress syndrome (ARDS). The secondary outcomes included acute cardiac or kidney injury, shock, coagulopathy, and venous thromboembolism. The main analysis was based on data from peer-reviewed studies. Summary estimates and the corresponding 95% prediction intervals (PIs) were obtained through meta-analyses. Results: A total of 44 peer-reviewed studies with 14,866 COVID-19 patients were included. In general, risk of bias was high. All-cause mortality was 10% overall (95% PI, 2 to 39%; 1687/14203 patients; 43 studies), 34% in patients admitted to intensive care units (95% PI, 8 to 76%; 659/2368 patients; 10 studies), 83% in patients requiring invasive ventilation (95% PI, 1 to 100%; 180/220 patients; 6 studies), and 75% in patients who developed ARDS (95% PI, 35 to 94%; 339/455 patients; 11 studies). On average, ARDS occurred in 14% of patients (95% PI, 2 to 59%; 999/6322 patients; 23 studies), acute cardiac injury in 15% (95% PI, 5 to 38%; 452/2389 patients; 10 studies), venous thromboembolism in 15% (95% PI, 0 to 100%; patients; 3 studies), acute kidney injury in 6% (95% PI, 1 to 41%; 318/4682 patients; 15 studies), coagulopathy in 6% (95% PI, 1 to 39%; 223/3370 patients; 9 studies), and shock in 3% (95% PI, 0 to 61%; 203/4309 patients; 13 studies). Conclusions: Mortality was very high in critically ill patients based on very low-quality evidence due to striking heterogeneity and risk of bias. The incidence of clinically relevant outcomes was substantial, although reported by only one third of the studies suggesting considerable underreporting. Trial registration: PROSPERO registration ID for this study is CRD42020177243 (https://www.crd.york.ac.uk/prospero/ display_record.php?RecordID=177243).

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio. GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. 1 The assumed risk is calculated from the median control group risk across the studies. 2 Downgraded (1 level) because 4 out of 8 trials were not double-blinded trials and for indirectness, as 2 out of 8 trials used dosages exceeding typical prophylactic dosages. 3 Downgraded (2 levels) because the 95% CI includes both negligible effect and appreciable benefit or appreciable harm; 3 out of 9 trials were not double-blinded, and 2 out of 9 trials did not use standard definitions to ascertain major bleeding. 4 Downgraded (2 levels) because the 95% CI includes both negligible effect and appreciable benefit or appreciable harm; risk of selective outcome reporting, with only 5 out of 10 trials reporting symptomatic PE.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio. GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. 1 The assumed risk is calculated from the median control group risk across the studies. 2 Downgraded (1 level) because 4 out of 8 trials were not double-blinded trials and for indirectness, as 2 out of 8 trials used dosages exceeding typical prophylactic dosages. 3 Downgraded (2 levels) because the 95% CI includes both negligible effect and appreciable benefit or appreciable harm; 3 out of 9 trials were not double-blinded, and 2 out of 9 trials did not use standard definitions to ascertain major bleeding. 4 Downgraded (2 levels) because the 95% CI includes both negligible effect and appreciable benefit or appreciable harm; risk of selective outcome reporting, with only 5 out of 10 trials reporting symptomatic PE.

Background Low muscle strength is a powerful predictor of negative health-related events and a key component of sarcopenia. The lack of normative values for muscle strength across ages hampers the practical appraisal of this parameter. The aim of the present study was to produce normative values for upper and lower extremity muscle strength across a wide spectrum of ages, in a large sample of community-dwellers recruited in the Longevity checkup (Lookup) 7+ project. Methods Lookup 7+ is an ongoing project that started in June 2015 and conducted in unconventional settings (i.e. exhibitions, malls, and health promotion campaigns) across Italy with the aim of fostering the adoption of healthy lifestyles in the general population. Candidate participants are eligible for enrolment if they are 18+ years and provide written informed consent. Upper and lower extremity muscle strength is assessed by handgrip strength and five-repetition chair-stand [5 × sit-to-stand (STS)] tests, respectively. Cross-sectional centile and normative values for handgrip strength and 5 × STS tests from age 18 to 80+ years were generated for the two genders. Smoothed normative curves for the two tests were constructed for men and women using the lambda-mu-sigma method. Results From 1 June 2015 to 30 May 2019, 11 448 participants were enrolled. The mean age of participants was 55.6 years (standard deviation: 11.5 years; range: 18-98 years), and 6382 (56%) were women. Normative values for handgrip strength and the 5 × STS test, both absolute and normalized by body mass index, were obtained for men and women, stratified by age groups. Values of upper and lower extremity muscle strength across ages identified three periods in life: an increase to peak in young age and early adulthood (18-24 years), preservation through midlife (25-44 years), and a decline from midlife onwards (45+ years). Conclusions Our study established age-specific and gender-specific percentile reference values for handgrip strength and the 5 × STS test. The normative curves generated can be used to interpret the assessment of muscle strength in everyday practice for the early detection of individuals with or at risk of sarcopenia.

Long-term performance of risk scores for venous thromboembolism in ambulatory cancer patients Running head: Prediction scores for cancer-associated thrombosis

Highlights Hyperinflammation in COVID-19 activates blood coagulation increasing thrombotic risk. Tocilizumab blocks IL-6 receptor and may improve inflammatory-induced hypercoagulability. Tocilizumab was associated with rapid and sustained coagulation improvement. These benefits were consistent independently of thromboprophylaxis dose.

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