ACL injury risk in invalid unanticipated drop jumps: kinetics, kinematics and neuromuscolar analysis

LAUREA MAGISTRALENegli sport ad alta intensità, gli atleti sono spesso chiamati a eseguire azioni motorie complesse, come ad esempio rapide decelerazioni, cambi di direzione e atterraggi su una sola gamba, in condizioni di incertezza e stress cognitivo. Questi scenari richiedono non solo un’adeguata preparazione fisica, ma anche un controllo sensorimotorio efficiente e una buona capacità di coordinazione anticipatoria. Sempre più evidente risulta essere che il fallimento di questi processi rappresenti un fattore chiave nelle lesioni non da contatto del legamento crociato anteriore (LCA), che spesso si verificano in assenza di traumi esterni, bensì durante azioni apparentemente banali come un atterraggio o un cambio di direzione improvviso. Questo studio ha indagato le differenze neuromuscolari e biomeccaniche tra atterraggi validi e non validi (bad) eseguiti durante drop jump in condizioni cognitive non programmate e impegnative da un punto di vista cognitivo. A differenza delle valutazioni tradizionali del rischio di lesione del LCA, che si concentrano principalmente su prove valide e su valori cinematici o dinamici discreti, come il picco durante l’atterraggio, questa ricerca adotta una prospettiva più ampia, includendo le prove fallite e analizzando sia la fase di pre-attivazione sia l’esecuzione dell’atterraggio, con l’obiettivo di individuare indicatori precoci di instabilità neuromuscolare e biomeccanica. I dati biomeccanici sono stati raccolti tramite un sistema di analisi del movimento e piattaforme di forza, mentre i segnali elettromiografici superficiali sono stati registrati da otto muscoli dell’arto dominante e del tronco. L’analisi ha incluso le forze di reazione al suolo, gli angoli articolari e i momenti articolari a livello di anca, ginocchio e caviglia. Sebbene la maggior parte delle differenze tra le condizioni non abbia raggiunto la significatività statistica in t test effettuati attraverso la Statistical Parametric Mapping (SPM), l’analisi statistica descrittiva sulle serie temporali ha evidenziato tendenze interessanti che potrebbero essere confermate da studi futuri: nei trials invalidi si osservano ritardi nell’attivazione della catena posteriore, maggiore dipendenza dal quadricipite e variazioni sottili nel carico articolare, in linea con meccanismi noti di lesione del LCA. L'unico risultato statisticamente significativo è emerso dall'analisi GRF, mostrando valori più bassi nella fase di posizione iniziale in trials invalidi rispetto a quelli validi. Mentre un GRF più basso è spesso visto come protettivo, nel nostro caso probabilmente riflette una scarsa stabilizzazione sulle piastre di forza, con conseguente gestione dell'impatto inefficace. L’analisi di movimenti non programmati, l’inclusione sia di salti validi che invalidi in valutazioni biomeccaniche relative all’infortunio al LCA potrebbe migliorare lo screening del rischio di infortunio, rivelando strategie compensatorie latenti e deficit nel controllo neuromuscolare anticipatorio. Questo approccio si rivela particolarmente rilevante in contesti sportivi, dove processi decisionali, fatica e distrazione giocano un ruolo cruciale nei meccanismi di lesione.In high-intensity sports settings, athletes are frequently required to execute complex motor actions, such as rapid decelerations, directional changes, and single-leg landings, under conditions of uncertainty and cognitive stress. These scenarios demand not only physical preparation but also efficient sensorimotor control and anticipatory coordination. Failures in these processes have been increasingly recognized as key contributors to non-contact anterior cruciate ligament (ACL) injuries, which often occur without external force but during seemingly routine tasks like landing or cutting. This study investigated the neuromuscular and biomechanical differences between valid and invalid (bad) drop jump landings performed under unanticipated, cognitively demanding conditions. Traditional ACL injury risk assessments often rely only on successful, controlled trials and focus on discrete kinematic or kinetic values, such as the peak recorded while landing. In contrast, this research adopts a broader perspective by including failed landings and analyzing both the pre-activation phase and landing execution, aiming to identify early indicators of neuromuscular and biomechanical instability that may otherwise go undetected. Biomechanical data of the dominant lower limb were collected using motion capture and force platforms, and surface electromyographic signals were recorded from eight muscles on the dominant side of trunk and lower body. The analysis included ground reaction forces, joint angles and moments at the hip, knee, and ankle. Although most differences between valid and bad trials did not reach statistical significance in t-tests through Statistical Parametric Mapping (SPM), the descriptive statistical analysis of time series revealed interesting trends that may be confirmed by future studies: bad trials showed delayed posterior muscular chain activation, increased quadriceps reliance, and subtle changes in joint loading consistent with known ACL injury mechanisms. The only statistically significant result emerged from GRF analysis, showing lower values in the early stance phase in bad trials compared to valid ones. While lower GRF is often seen as protective, in our case it likely reflects poor stabilization on the force plates, resulting in ineffective impact management. The analysis of unanticipated tasks, including both successful and unsuccessful jumps in ACL injury-related biomechanical assessments could enhance injury screening by revealing subtle compensatory strategies and deficits in anticipatory neuromuscular control. This approach may be especially relevant in sports contexts, where decision-making, fatigue, and distraction often play a critical role in injury mechanisms

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival