Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the CNS. Myelin-specific CD4⁺ Th lymphocytes are known to play a major role in both MS and its animal model experimental autoimmune encephalomyelitis (EAE). CCR7 is a critical element for immune cell trafficking and recirculation, that is, lymph node homing, under homeostatic conditions; blocking CCR7⁺ central memory cells from egress of lymph nodes is a therapeutic approach in MS. To define the effect of CD4⁺ T cell–specific constitutive deletion of CCR7 in the priming and effector phase in EAE, we used an active EAE approach in T cell reconstituted Rag1^−/− mice, as well as adoptive transfer EAE, in which mice received in vitro–primed CCR7^−/− or CCR7^+/+ myelin Ag TCR-transgenic 2d2 Th17 cells. Two-photon laser scanning microscopy was applied in living anesthetized mice to monitor the trafficking of CCR7-deficient and wild-type CD4⁺ T cells in inflammatory lesions within the CNS. We demonstrate that CD4⁺ T cell–specific constitutive deletion of CCR7 led to impaired induction of active EAE. In adoptive transfer EAE, mice receiving in vitro–primed CCR7^−/− 2d2 Th17 cells showed similar disease onset as mice adoptively transferred with CCR7^+/+ 2d2 Th17 cells. Using two-photon laser scanning microscopy CCR7^−/− and CCR7^+/+ CD4⁺ T cells did not reveal differences in motility in either animal model of MS. These findings indicate a crucial role of CCR7 in neuroinflammation during the priming of autoimmune CD4⁺ T cells but not in the CNS.

Background: Calcaneal apophysitis, or Sever's disease, is the most common cause of heel pain in childhood and adolescence. It is regarded as an overuse syndrome. Studies on the incidence of calcaneal apophysitis in young athletes and their associated return-to-play time are lacking in the current literature. The aim of our current study was to identify the incidence of calcaneal apophysitis in professional youth soccer, the associated time to return-to-play, predisposing factors and their impact on time to return-to-play. Methods: Retrospective evaluation of injury data gathered from a German youth soccer academy in the years 2009–2018. In total, 4326 injury cases in 612 players were included in the study. The diagnosis and the follow-up visits were carried out in a weekly consultation hour at the youth academy. Results: During the observation period of 10 years, 22 cases of calcaneal apophysitis were detected. The incidence of calcaneal apophysitis per 100 athletes per year was found to be 0.36. The mean age of the affected athletes at the time of diagnosis was 11.8 ± 2.1 years (MW ± SD). The complaints were unilateral in 20 and bilateral in two cases. Three of the 22 detected cases of calcaneal apophysitis (13.6%) were recurrent injuries. The mean time to return-to-play of the affected athletes was 60.7 ± 64.9 days (MW ± SD). Athletes with recurrent complaints showed longer recovery time and time to return-to-play when compared to players with primary diagnosed disease. Our results could show that neither age nor body mass index at the time of diagnosis had an impact on time to return-to-play. Conclusions: This is the first study investigating the incidence of calcaneal apophysitis and the associated time to return-to-play in youth elite soccer. Calcaneal apophysitis results in substantial time loss for the athletes. Further prospective clinical studies are required to fully understand the etiology and risk factors for calcaneal apophysitis and therefore develop preventive strategies.

Objective: Natalizumab is known to prevent T-helper cells entering the central nervous system (CNS). We hypothesize that more pathogenic T-helper cells are present outside the CNS and a possible relationship to disease severity. Methods: Characterization and enrichment of human CD4+IL-17+ cells were performed ex vivo using peripheral blood mononuclear cells from natalizumab-treated relapsing-remitting multiple sclerosis (RRMS) patients ( n = 33), untreated RRMS patients ( n = 13), and healthy controls ( n = 33). Magnetic resonance imaging (MRI) scans were performed routinely for patients. Results: Lymphocytes were elevated in peripheral blood of natalizumab-treated patients compared to untreated patients and healthy controls. Whereas group comparison for CD4+IL-17+ numbers also differed, CD4+IFN-γ+ and CD4+IL-22+ counts were not increased. CD4+IL-17+ cells not only expressed but also secreted IL-17. In natalizumab-treated patients, IL-17+ cell frequency was found to correlate with T1-hypointense lesions, but was not an indicator for rebound activity after treatment discontinuation, except in one patient who experienced a fulminant rebound, and interestingly, in whom the highest IL-17+ cell levels were observed. Conclusion: Increased lymphocytes and CD4+IL-17+ cells in the blood of RRMS patients receiving natalizumab corroborate the drug’s mechanism of action, that is, blocking transmigration to CNS. Correlation between IL-17-expressing lymphocytes and T1-hypointense lesions underlines the important role of these cells in the disease pathology.

Neutral coronal leg alignment is known to be important for postoperative outcome in total knee arthroplasty (TKA). Customized individually made implants (CIM) instrumented with patient-specific cutting guides are an innovation aiming to increase the precision and reliability of implant positioning and reconstruction of leg alignment. We aimed to compare reconstruction of the hip–knee–ankle angle (HKA) of the novel CIM system iTotal™ CR G2 (ConforMIS Inc.) to a matched cohort of the off-the-shelf (OTS) knee replacement system Vanguard™ CR (Zimmer Biomet). Retrospective analysis of postoperative coronal full-leg weight-bearing radiographs of 562 TKA (283 CIM TKA, 279 OTS TKA) was conducted. Via a medical planning software, HKA and rotation of the leg were measured in postoperative radiographs. HKA was then adjusted for rotational error, and 180° ± 3° varus/valgus was defined as the target zone HKA. Corrected postoperative HKA in the CIM group was 179.0° ± 2.8° and 179.2° ± 3.1° in the OTS group (p = 0.34). The rate of outliers, outside of the ±3° target zone, was equal in both groups (32.9%). Our analysis showed that TKA using patient-specific cutting guides and implants and OTS TKA implanted with conventional instrumentation resulted in equally satisfying restoration of the coronal leg alignment with less scattering in the CIM group.

Skeletal muscle injuries in competitive sports cause lengthy absences of athletes from tournaments. This is of tremendous competitive and economic relevance for both the athletes and their respective clubs. Therapy for structural muscle lesions aims to promote regeneration and fast-track return-to-play. A common clinical treatment strategy for muscle injuries is the intramuscular injection of calf blood compound and the homeopathic drug, Tr14. Although the combination of these two agents was reported to reduce recovery time, the regulatory mechanism whereby this occurs remains unknown. In this in vivo study, we selected a rat model of mechanical muscle injury to investigate the effect of this combination therapy on muscle regeneration. Gene expression analysis and histological images revealed that this combined intramuscular injection for muscle lesions can enhance the expression of pro-myogenic genes and proteins and accelerate muscle regeneration. These findings are novel and depict the positive effects of calf blood compound and the homeopathic drug, Tr14, which are utilized in the field of Sports medicine.