Introduction: Chondral and soft tissue injuries can be associated with first time patellar dislocation, but it is unclear how common they are, and which tissues are affected. A systematic review of the literature was performed to investigate the frequency, location, and extent of chondral and medial patellofemoral ligament (MPFL) injuries in patients following first time patellar dislocation. Methods: This systematic review was conducted according to the PRISMA guidelines. PubMed, Google Scholar, Embase, and Web of Science databases were accessed in November 2021. All the published clinical studies reporting the frequency, location, and extent of soft tissue lesions following first time patellar dislocation were accessed. Studies reporting data on habitual, congenital, or recurrent patellofemoral instability were excluded. Results: Data from 42 articles (2254 patients, mean age 21.6 ± 7.3 years) were retrieved. Ninety-eight percent of patients who experienced first time patellar dislocation demonstrated MPFL rupture at MRI. Forty-eight percent of MPFL ruptures were located at the patellar side, 34% at the femoral insertion site, and 18% in the midportion. Eighty-five percent of patients showed signs of patellar chondral damage at MRI, and trochlear chondral injuries were evidenced in 47% of patients. Intra-articular loose bodies were observed in 11.5% of patients. At arthroscopy, the medial facet and the crest of the patella more commonly exhibited chondral lesions than the lateral facet and femoral trochlea. Conclusions: Most patients suffer chondral damage and MPFL tears following after a first time patellar dislocation.

Background and Objectives: Starting in early December 2019, the novel Coronavirus Disease (COVID-19) from infection with COVID-19 has caused a global pandemic. Many aspects of its pathogenesis and related clinical consequences are still unclear. Early diagnosis and dynamic monitoring of prognostic factors are essential to improve the ability to manage COVID-19 infection. This study aimed to provide an account of the role played by vitamins C and D on the onset, progression and severity of COVID-19. Clinical features and infection-related risk factors are also briefly discussed. Material and Methods: In March 2022, the main online databases were accessed. All the articles that investigate the possible role of vitamins C and D on COVID-19 susceptibility, severity and progression were considered. Results: The current evidence on vitamin C and D supplementation in patients with COVID-19 infection is inconsistent and controversial. In some studies, vitamins were used as coadjuvant of a formal experimental therapy, while in others as main treatment. Ethnicity and hospital setting (inpatient/outpatient) were also variable. Moreover, there was no consensus between studies in administration protocol: high heterogeneity in dosage, administration, and duration of the treatment were evident. Finally, some studies administered vitamins pre- and/or during COVID infection, in patients with different risk factors and infection severity. Conclusions: While waiting to develop a targeted, safe and effective therapy, it is important to investigate individual predisposition and proper disease management. Concluding, available data on the use of nutraceuticals in COVID-19 are inconsistent. However, there is a lack of evidence-based guidelines which recommend vitamin C and D supplementation in patients with COVID-19, and results from high quality randomised controlled trials (RCTs) are inconsistent. Current investigations so far are mostly observational, and include a relatively small sample size which can lead to biased results. Large-scale multicentre studies are therefore needed.

The aim of this study was to investigate the effect of triiodothyronine (T3) on tendon specific markers and cytokines expression of stem cells extracted from human tendons. Indeed, thyroid hormones have been reported to be protective factors, maintaining tendons’ homeostasis, whereas tendinopathy is believed to be related to a failed healing response. Healthy and tendinopathic human tendons were harvested to isolate tendon stem/progenitor cells (TSPCs). TSPCs obtained from pathological samples showed gene expression and morphological modifications at baseline in comparison with cells harvested from healthy tissues. When cells were maintained in a medium supplemented with T3 (10⁻⁶ M), only pathological populations showed a significant upregulation of tenogenic markers (DCN, TNC, COL1A1, COL3A1). Immunostaining revealed that healthy cells constantly released type I collagen, typical of tendon matrix, whereas pathological ones overexpressed and secreted type III collagen, typical of scarred and impaired tissue. Pathological cells also overexpressed pro- and anti-inflammatory cytokines, suggesting an impaired balance in the presence of T3, without STAT3 activation. Moreover, DKK-1 was significantly high in the culture medium of pathological cell cultures and was reversed by T3. This study opens perspectives on the complex biochemical alteration of cells from pathological tendons, which may lead to the chronic disease context with an impaired extracellular matrix.

Sustained oxidative stress and inflammation have been reported as the major factors responsible for the failure of tendon healing during rotator cuff tears (RCTs) and rotator cuff disease (RCD). Although, their therapeutic management remains still challenging. Carbonic anhydrases (CAs) are involved in many pathological conditions, and the overexpression of both CA9 and 12 in inflamed joints has been recently reported. Consequently, a selective CA9/12 inhibition could be a feasible strategy for improving tendon recovery after injury. In addition, since carbon monoxide (CO) has been proven to have an important role in modulating inflammation, CO releasing molecules (CORMs) can be also potentially suitable compounds. The present study aims at evaluating five newly synthesized dual-mode acting CA inhibitors (CAIs)-CORMs compounds, belonging to two chemical scaffolds, on tendon-derived human primary cells under H₂O₂ stimulation in comparison with Meloxicam. Our results show that compounds 2 and 7 are the most promising of the series in counteracting oxidative stress-induced cytotoxicity and display a better profile in terms of enhanced viability, decreased LDH release, and augmented tenocyte proliferation compared to Meloxicam. Moreover, compound 7, as a potent superoxide scavenger, exerts its action inhibiting NF-ĸB translocation and downregulating iNOS, whereas compound 2 is more effective in increasing collagen I deposition. Taken together, our data highlight a potential role of CA in RCTs and RCD and the prospective effectiveness of compounds acting as CAI-CORM during inflammation.

Rotator cuff tendon (RCT) disease results from multifactorial mechanisms, in which inflammation plays a key role. Pro-inflammatory cytokines and tendon stem cell/progenitor cells (TSPCs) have been shown to participate in the inflammatory response. However, the underlying molecular mechanism is still not clear. In this study, flow cytometry analyses of different subpopulations of RCT-derived TSPCs demonstrate that after three days of administration, TNFα alone or in combination with IFNγ significantly decreases the percentage of CD146+CD49d+ and CD146+CD49f+ but not CD146+CD109+ TSPCs populations. In parallel, the same pro-inflammatory cytokines upregulate the expression of CD200 in the CD146+ TSPCs population. Additionally, the TNFα/IFNγ combination modulates the protein expression of STAT1, STAT3, and MMP9, but not fibromodulin. At the gene level, IRF1, CAAT (CAAT/EBPbeta), and DOK2 but not NF-κb, TGRF2 (TGFBR2), and RAS-GAP are modulated. In conclusion, although our study has several important limitations, the results highlight a new potential role of CD200 in regulating inflammation during tendon injuries. In addition, the genes analyzed here might be new potential players in the inflammatory response of TSPCs.