Background: Anterior cruciate ligament (ACL) rupture is a serious injury with a high prevalence worldwide, and subsequent ACL reconstructions (ACLR) appear to be most commonly performed using hamstring-derived (semitendinosus tendon) autografts. Recovery of maximal muscle strength to ≥90% of the healthy contralateral limb is considered an important criterion for safe return to sports. However, the speed of developing muscular force (ie, the rate of force development [RFD]) is also important for the performance of many types of activities in sports and daily living, yet RFD of the knee extensor and flexor muscles has apparently never been examined in patients who undergo ACLR with hamstring autograft (HA). Purpose: To examine potential deficits in RFD, maximal muscle strength (ie, maximal voluntary isometric contraction [MVIC]), and functional capacity of ACLR-HA limbs in comparison with the healthy contralateral leg and matched healthy controls 3 to 9 months after surgery. Study Design: Cross-sectional study; Level of evidence: 3. Methods: A total of 23 young patients who had undergone ACLR-HA 3 to 9 months earlier were matched by age to 14 healthy controls; both groups underwent neuromuscular screening. Knee extensor and flexor MVIC and RFD, as well as functional capacity (single-leg hop for distance [SLHD] test, timed single-leg sit-to-stand [STS] test), were assessed on both limbs. Furthermore, patient-reported knee function (Knee injury and Osteoarthritis Outcome Score) was assessed. Results: Knee extensor and flexor MVIC and RFD were markedly compromised in ACLR-HA limbs compared with healthy contralateral limbs (MVIC for extensor and flexor, 13% and 26%, respectively; RFD, 14%-17% and 32%-39%) and controls (MVIC, 16% and 31%; RFD, 14%-19% and 30%-41%) ( P < .05-.001). Further, ACLR-HA limbs showed reduced functional capacity (reduced SLHD and STS performance) compared with contralateral limbs (SLHD, 11%; STS, 14%) and controls (SLHD, 20%; STS, 31%) ( P < .01-.001). Strength (MVIC) and functional (SLHD) parameters were positively related to the duration of time after surgery ( P < .05), although this relationship was not observed for RFD and STS. Conclusion: Knee extensor and flexor RFD and maximal strength, as well as functional single-leg performance, remained substantially reduced in ACLR-HA limbs compared with noninjured contralateral limbs and healthy controls 3 to 9 months after reconstructive surgery.

Background and methods Inflammation is a hallmark of cancer and its progression. Plasma levels of C‐reactive protein (CRP), interleukin‐6 (IL‐6) and YKL‐40 reflect inflammation, and are elevated in patients with cancer. This study investigated whether plasma CRP, IL‐6 and YKL‐40 had diagnostic value in 753 patients referred with nonspecific signs and symptoms of cancer to a diagnostic outpatient clinic. Results In total, 111 patients were diagnosed with cancer within 3 months and 30 after 3 months. CRP, IL‐6 and YKL‐40 were elevated in 44%, 60% and 45% of the cancer patients, and in 15%, 33% and 25% of the patients without cancer. Elevated levels of all three markers were associated with risk of cancer within 3 months: CRP (odds ratio (OR) 4.41, 95% confidence interval (CI) 2.86–6.81), IL‐6 (OR = 2.89, 1.91–4.37) and YKL‐40 (OR = 2.42, 1.59–3.66). Multivariate explorative analyses showed that increasing values were associated with the risk of getting a cancer diagnosis (continuous scale: CRP (OR = 1.28, 1.12–1.47), carcinoembryonic antigen (CEA) (OR = 1.61, 1.41–1.98), CA19‐9 (OR = 1.15, 1.03–1.29), age (OR = 1.29, 1.02–1.63); dichotomized values: CRP (OR = 2.54, 1.39–4.66), CEA (OR = 4.22, 2.13–8.34), age (OR = 1.42, 1.13–1.80)). CRP had the highest diagnostic value (area under the curve = 0.69). Combined high CRP, IL‐6 and YKL‐40 was associated with short overall survival (HR = 3.8, 95% CI 2.5–5.9, p < 0.001). Conclusion In conclusion, plasma CRP, IL‐6 and YKL‐40 alone or combined cannot be used to identify patients with cancer, but high levels were associated with poor prognosis. CRP may be useful to indicate whether further diagnostic evaluation is needed when patients present with nonspecific signs and symptoms of cancer.

Genome-wide cfDNA fragmentation patterns have previously been demonstrated to distinguish with high sensitivity and specificity between plasma samples from individuals with and without cancer. To further evaluate cfDNA fragmentation as a blood-based screening test for cancer, we have used low coverage whole genome sequencing to analyze plasma samples from 280 patients referred to an advanced diagnostic center due to non-organ specific signs and symptoms of cancer. Within three months of inclusion, 74 of these patients were diagnosed with one of 16 different solid cancers while 206 patients did not have cancer. Using an improved version of our genome-wide cfDNA fragmentation analyses, we observed high performance in distinguishing cancer and non-cancer samples (AUC=0.92, 95% CI 0.88-0.96), including lung cancer (n=12, AUC=0.91, 95% CI 0.80-1.00) and colorectal cancer (n=12, AUC=0.94, 95% CI 0.89-0.99). Although many of the patients in this cohort had other common illnesses including cardiovascular, autoimmune, and inflammatory diseases, the machine learning models of cfDNA fragmentation were able to detect cancer with high sensitivity and specificity. These data support the development of genome-wide cfDNA fragmentation analyses as a non-invasive detection screening approach for both single and multiple cancers. Citation Format: Jacob Carey, Alessandro Leal, Bryan Chesnick, Denise Butler, Michael Rongione, Sian Jones, Rob Scharpf, Mette Villadsen, Stig E. Bojesen, Julia S. Johansen, Claus L. Feltoft, Victor E. Velculescu, Nicholas C. Dracopoli. Detecting cancer using genome-wide cfDNA nucleosomal fragmentation in a prospective multi cancer cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 570.