Longitudinal characterisation of haematological and biochemical parameters in cancer patients prior to and during COVID-19 reveals features associated with outcome.

BACKGROUND: Cancer patients are at increased risk of death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer and its treatment affect many haematological and biochemical parameters, therefore we analysed these prior to and during coronavirus disease 2019 (COVID-19) and correlated them with outcome. PATIENTS AND METHODS: Consecutive patients with cancer testing positive for SARS-CoV-2 in centres throughout the United Kingdom were identified and entered into a database following local governance approval. Clinical and longitudinal laboratory data were extracted from patient records. Data were analysed using Mann-Whitney U test, Fisher's exact test, Wilcoxon signed rank test, logistic regression, or linear regression for outcomes. Hierarchical clustering of heatmaps was performed using Ward's method. RESULTS: In total, 302 patients were included in three cohorts: Manchester (n = 67), Liverpool (n = 62), and UK (n = 173). In the entire cohort (N = 302), median age was 69 (range 19-93 years), including 163 males and 139 females; of these, 216 were diagnosed with a solid tumour and 86 with a haematological cancer. Preinfection lymphopaenia, neutropaenia and lactate dehydrogenase (LDH) were not associated with oxygen requirement (O2) or death. Lymphocyte count (P < 0.001), platelet count (P = 0.03), LDH (P < 0.0001) and albumin (P < 0.0001) significantly changed from preinfection to during infection. High rather than low neutrophils at day 0 (P = 0.007), higher maximal neutrophils during COVID-19 (P = 0.026) and higher neutrophil-to-lymphocyte ratio (NLR; P = 0.01) were associated with death. In multivariable analysis, age (P = 0.002), haematological cancer (P = 0.034), C-reactive protein (P = 0.004), NLR (P = 0.036) and albumin (P = 0.02) at day 0 were significant predictors of death. In the Manchester/Liverpool cohort 30 patients have restarted therapy following COVID-19, with no additional complications requiring readmission. CONCLUSION: Preinfection biochemical/haematological parameters were not associated with worse outcome in cancer patients. Restarting treatment following COVID-19 was not associated with additional complications. Neutropaenia due to cancer/treatment is not associated with COVID-19 mortality. Cancer therapy, particularly in patients with solid tumours, need not be delayed or omitted due to concerns that treatment itself increases COVID-19 severity.

Post-exercise cardiac troponin release is related to exercise training history.

Marathon running can increase circulating cardiac troponin above the diagnostic criteria for myocardial infarction. We determined whether prior-exercise experience (training history) might be related to the magnitude of immediate post-race troponin release following completion of the London Marathon in a group of non-elite runners. Using a prospective study design, 52 runners were recruited into either HIGH T-E (trained-experience) (n=27) or LOW T-E (n=25) groups. Cardiac troponin I (cTnI) release following race completion was compared between these 2 groups. To examine relationships between cTnI release and participant demographic and indices of prior training experience an additional 52 runners who did not meet the criteria for either the HIGH T-E or LOW T-E groups were also recruited. The combined data from all 104 runners was analysed using multivariate linear regression analysis. The results revealed a significant difference in post marathon circulating cTnI between LOW T-E runners (median: 0.11 µg/L; interquartile range [IQR]: 0.03-0.18 µg/L) and HIGH T-E runners (median: 0.03 µg/L; IQR 0.02-0.057 µg/L) (p<0.05). Average miles run per week in the last 3 years, a marker of total training experience, encompassing training volume and duration, was negatively associated with post-marathon cTnI release (p<0.001).In conclusion, exercise-induced cTnI release is strongly related to previous training experience.

Correlates of knee laxity change in early rehabilitation after anterior cruciate ligament reconstruction.

Factors other than ligament graft length (knee ROM, knee swelling, initial knee laxity) may need to be accounted for in interpreting changes in knee laxity during rehabilitation following anterior cruciate ligament reconstruction (ACLR) surgery. Twenty-three patients recovering from ACLR surgery (16 M, 7 F, age mean = 30) were tested at 2 and 6 weeks after ACLR with knee laxity measured using th Knee Signature System arthrometer, passive ROM with a standard goniometer and swelling by measuring knee circumference at the mid-patella level using a cloth measuring tape. Spearman correlation coefficients (in parentheses) were calculated using rankings of the change in the injured minus uninjured knee laxity as the dependent variable and the following independent variables: pre-test injured minus uninjured knee laxity (ranked; -0.457; statistically significant two-tailed P < 0.05); change in injured knee maximum extension relative to the uninjured side (ranked; 0.127); change in injured knee maximum flexion relative to the uninjured side (unranked; -0.073); and change in the injured minus uninjured knee girth (unranked; -0.159). These results indicate that consideration should be given to the patient's knee laxity at the start of intervention when using changes in laxity to guide rehabilitation after ACLR.

Effects of open versus closed kinetic chain training on knee laxity in the early period after anterior cruciate ligament reconstruction.

Knee extensor resistance training using open kinetic chain (OKC) exercise for patients recovering from anterior cruciate ligament reconstruction (ACLR) surgery has lost favour mainly because of research indicating that OKC exercise causes greater ACL strain than closed kinetic chain (CKC) exercise. In this prospective, randomized clinical trial the effects of these two regimes on knee laxity were compared in the early period after ACLR surgery. Thirty-six patients recovering from ACLR surgery (29 males, 7 females; age mean = 30) were tested at 2 and 6 weeks after ACLR with knee laxity measured using the Knee Signature System arthrometer. Between tests subjects trained using either OKC or CKC resistance of their knee and hip extensors in formal physical therapy sessions three times per week. Following adjustment for site of treatment, pretraining injured knee laxity, and untreated knee laxity at post-training, the use of OKC exercise, when compared to CKC exercise, was found to lead to a 9% increase in looseness with a 95% confidence interval of -8% to +29%. These results indicate that the great concern about the safety of OKC knee extensor training in the early period after ACLR surgery may not be well founded.