Most Anterior Cruciate Ligament Injuries in Professional Athletes Occur Without Contact to the Injured Knee: A Systematic Review of Video Analysis Studies.

PURPOSE: To systematically review studies utilizing video analyses to evaluate anterior cruciate ligament (ACL) injury mechanisms in athletes during sport to better understand risk factors and the potential for injury prevention. METHODS: A literature search was conducted in accordance with the 2020 PRISMA guidelines statement using SCOPUS, PubMed, Medline, and the Cochrane Central Register for Controlled Trials from database inception through June 2023. Inclusion criteria including studies reporting on ACL injury mechanisms occurring in athletes based on video analysis. Athlete demographics, injury mechanisms, position of the lower extremity, and activity at the time of injury were recorded. RESULTS: A total of 13 studies, consisting of 542 athletes, met inclusion criteria. The majority of athletes competed at the professional level (91%, n=495/542) with 79% (n=422/536) of athletes being male. The most common sports were soccer (33%, n=178/542) and American football (26%, n=140/542). The most common injury mechanism was non-contact in 42.9% (n=230/536) of athletes, followed by indirect contact (32.6%, n=175/536) and direct contact (22.4%, n=120/536). The most common position of injury was with a planted foot ( 91.7%, n=110/120), full or near full knee extension ( 84.4%, n=49/58), and axial loading ( 81.3%, n=87/107). Injuries commonly involved a deceleration/shift in momentum ( 50.4%, n=123/244) or pivoting maneuver ( 36.1%, n=77/213). At the time of injury, the knee commonly fell into valgus ( 76.8%, n=225/293) with associated internal (53.5%, n=46/86) or external tibiofemoral rotation ( 57.7%, n=101/175). CONCLUSIONS: The majority of ACL injuries, when evaluated by video analysis, involve professional athletes participating in soccer and American football. The most common injury mechanism occurred without contact with the knee in extension during a deceleration or momentum shift, with resultant valgus and rotational force across the knee. LEVEL OF EVIDENCE: IV; Systematic review of level IV studies.

Isolated, Proximal Tibiofibular Injuries in Athletic Patients: A Critical Analysis Review.

While infrequently reported, isolated injuries to the proximal tibiofibular (TF) joint primarily occur in young, athletic patients participating in sporting activities requiring explosive, high impact movements, increasing the risk for potential twisting injuries, especially across a hyperflexed knee. The proximal TF joint is stabilized by bony, muscular and ligamentous structures, including both the anterior and posterior proximal tibiofibular complexes, with the anterior complex providing more robust stability. Proximal TF injuries frequently involve anterior and lateral displacement of the proximal fibula relative to its native articulation with the tibia. Proper diagnosis is dependent on careful and meticulous history and physical examination, as missed injuries are common, leading to the potential for continued pain, weakness and disability, especially in athletic patients. While spontaneous joint reduction has been reported, injuries may require formal closed reduction, with irreducible and chronic injuries requiring open reduction and stabilization, with recent investigations reporting satisfactory outcomes following anatomic reconstruction of the proximal TF ligament.

Correlation between articular cartilage status on outcomes and survivorship following meniscal allograft transplantation: A systematic review.

PURPOSE: To conduct a systematic review evaluating potential correlations between preoperative articular cartilage integrity on outcomes and survivorship in patients undergoing meniscal allograft transplantation (MAT). METHODS: A literature search was performed by querying SCOPUS, PubMed, Medline, and the Cochrane Central Register for Controlled Trials from database inception through May 2023 according to the 2020 PRISMA statement. Inclusion criteria were limited to studies reporting on outcomes and survivorship following MAT based on preoperative cartilage status. RESULTS: Sixteen studies, consisting of 1723 patients (n = 1758 total menisci), were identified in six level III and 10 level IV evidence studies. There was high heterogeneity in cartilage grading scales, reporting of concomitant cartilage procedures, and indications for MAT based on osteoarthritis. Patients with lower limb malalignment were either excluded or corrected with an osteotomy. MAT failure rate was reported in nine studies, with four studies reporting a greater rate of failure in knees with higher degrees of cartilage damage. Eight studies reported on clinical outcomes based on cartilage grade, with two studies reporting significant differences in clinical outcomes based on cartilage grade. Of the five studies reporting management of full-thickness chondral defects with cartilage surgery, three studies reported no significant difference in survivorship based on preoperative cartilage grade, while one study reported lower survivorship and one study reported unclear results. No studies found significant differences in survivorship and outcomes between medial and lateral MAT. CONCLUSIONS: Conflicting results and high variability in reporting of concomitant cartilage repair and indications for MAT exist in studies evaluating the efficacy of MAT based on articular cartilage status. The degree of preoperative chondral damage did not have a strong relationship with clinical outcomes following MAT. Higher degrees of cartilage damage were associated with higher MAT failure rates, with possible improvement in survivorship when treated with an appropriate cartilage procedure. LEVEL OF EVIDENCE: Level IV.

Systematic Review and Meta-analysis of Clinical Outcomes After Management of Posterior Cruciate Ligament Tibial Avulsion Fractures.

Background: There is no consensus regarding the management of posterior cruciate ligament (PCL) avulsion fractures and the expected outcomes after treatment. Purpose: To systematically review clinical outcomes and complications after management of tibial-sided avulsion fractures of the PCL. Study Design: Systematic review; Level of evidence, 4. Methods: A literature search of Scopus, PubMed, Medline, and the Cochrane Central Register for Controlled Trials was performed in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included were studies with evidence levels 1 to 4 that reported clinical outcomes after treatment of PCL tibial-sided avulsion fractures in humans. The quality of the included studies was performed using the Methodological Index for Non-Randomized Studies (MINORS) criteria. A meta-analysis was performed for patient-reported outcome measures using random-effects modeling with 95% CIs. Results: A total of 58 studies published between 1999 and 2022 were identified. The mean MINORS score was 9.90 ± 4.12, indicating overall low-quality evidence with high risk of bias. The studies comprised 1440 patients (mean age, 32.59 ± 5.69 years; 75.2% males) with a mean follow-up of 26.9 ± 19.6 months (range, 5.3-126 months). Most patients were treated with open surgery (63.6%), followed by arthroscopic surgery (29.7%) and nonoperative treatment (6.7%). All patients reported significant posttreatment improvement in both subjective and objective outcomes (P < .05 for all). Arthroscopic surgery was associated with lower postoperative posterior tibial translation compared with open surgery (range, 0.6-3.2 vs 1.7-3.1 mm), greater preoperative to postoperative improvement in Lysholm score (54.6 vs 48.8; P < .0001), higher postoperative Tegner score (6.64 ± 1.03 vs 6.14 ± 2.29; P = .0448), and a higher rate of return to sport (100% vs 89.5%; P = .009). Nonoperative management was associated with a significantly lower fracture union rate (87% vs 99.1%; P < .0001) and greater postoperative side-to-side posterior translation (4.9 ± 4.3 mm) when compared with operative management. Conclusion: Although nonoperative and surgical management of PCL tibial avulsion fractures resulted in high rates of fracture union and improvement in functional outcome scores and a low incidence of complications, nonoperative treatment yielded a high side-to-side posterior displacement (>4 mm) with a lower rate of fracture union compared to surgical treatment.

Return to Sport After Nonoperative Management of Elbow Ulnar Collateral Ligament Injuries: A Systematic Review and Meta-analysis.

BACKGROUND: Elbow ulnar collateral ligament (UCL) injuries can result in significant functional impairment in throwing and overhead athletes. UCL reconstruction and repair are proven treatments to restore stability, but the efficacy of nonoperative management is unclear. PURPOSE: To determine the rate of return to sports (RTS) and return to previous level of play (RTLP) in athletes sustaining medial elbow ulnar collateral ligament (UCL) injuries treated nonoperatively. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A literature search was performed using Scopus, PubMed, Medline, the Cochrane Database for Systematic Review, and the Cochrane Central Register for Controlled Trials according to the 2020 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Inclusion criteria were limited to level 1 to 4 human studies reporting on RTS outcomes after nonoperative management of UCL injuries. RESULTS: A total of 15 studies, consisting of 365 patients with a mean age of 20.45 ± 3.26 years, were identified. Treatment primarily consisted of platelet-rich plasma (PRP) injections with physical therapy (n = 189 patients; n = 7 studies) versus physical therapy alone (n = 176 patients; n = 8 studies). The overall RTS rate was 79.7% and the overall RTLP rate was 77.9%. Increasing UCL injury severity grade was associated with lower RTS rates. The RTS rate for proximal tears (89.7%; n = 61/68) was significantly greater than that for distal tears (41.2%; n = 14/34) (P < .0001). No significant difference in RTS rate was seen in patients treated with PRP versus those who did not receive PRP (P = .757). CONCLUSION: For athletes undergoing nonoperative management of UCL injuries, the overall RTS and RTLP rates were 79.7% and 77.9%, respectively, with excellent outcomes in grade 1 and grade 2 UCL injuries, specifically. The RTS rate for proximal tears was significantly higher than that for distal tears. Athletes were most commonly treated with PRP injection and physical therapy.

Consistent Indications and Good Outcomes Despite High Variability in Techniques for Two-Stage Revision Anterior Cruciate Ligament Reconstruction: A Systematic Review.

PURPOSE: To systematically review the current literature regarding the indications, techniques, and outcomes after 2-stage revision anterior cruciate ligament reconstruction (ACLR). METHODS: A literature search was performed using SCOPUS, PubMed, Medline, and the Cochrane Central Register for Controlled Trials according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta Analyses statement. Inclusion criteria was limited to Level I-IV human studies reporting on indications, surgical techniques, imaging, and/or clinical outcomes of 2-stage revision ACLR. RESULTS: Thirteen studies with 355 patients treated with 2-stage revision ACLR were identified. The most commonly reported indications were tunnel malposition and tunnel widening, with knee instability being the most common symptomatic indication. Tunnel diameter threshold for 2-stage reconstruction ranged from 10 to 14 mm. The most common grafts used for primary ACLR were bone-patellar tendon-bone (BPTB) autograft, hamstring graft, and LARS (polyethylene terephthalate) synthetic graft. The time elapsed from primary ACLR to the first stage surgery ranged from 1.7 years to 9.7 years, whereas the time elapsed between the first and second stage ranged from 21 weeks to 13.6 months. Six different bone grafting options were reported, with the most common being iliac crest autograft, allograft bone dowels, and allograft bone chips. During definitive reconstruction, hamstring autograft and BPTB autograft were the most commonly used grafts. Studies reporting patient-reported outcome measures showed improvement from preoperative to postoperative levels in Lysholm, Tegner, and objective International Knee and Documentation Committee scores. CONCLUSIONS: Tunnel malpositioning and widening remain the most common indications for 2-stage revision ACLR. Bone grafting is commonly reported using iliac crest autograft and allograft bone chips and dowels, whereas hamstring autograft and BPTB autograft were the most used grafts during the second-stage definitive reconstruction. Studies showed improvements from preoperative to postoperative levels in commonly used patient reported outcomes measures. LEVEL OF EVIDENCE: Level IV, systematic review of Level I, III, and IV studies.

Complication Rates After Medial Patellofemoral Ligament Reconstruction Range From 0% to 32% With 0% to 11% Recurrent Instability: A Systematic Review.

PURPOSE: To review the incidence of complications following primary medial patellofemoral ligament (MPFL) reconstruction for recurrent patellar instability. METHODS: A literature search was conducted by querying PubMed and Scopus databases from database inception through August 2022 according to the 2020 Preferred Reporting Items for Systematic Review and Meta-analysis guidelines using the terms "Medial Patellofemoral Ligament," "MPFL," "reconstruction," "patellar," and "instability." Inclusion criteria included studies reporting complications following primary MPFL reconstruction for recurrent patellar instability. Exclusion criteria consisted of studies reporting on patients undergoing concurrent osteotomy procedures, revision reconstruction, and biomechanical or anatomic studies. The incidence of specific complications was aggregated from the included studies. RESULTS: Twenty-eight studies, consisting of 1,478 patients (n = 1521 knees), with a mean age of 23.3 years (mean range, 19-34.3 years) were identified. The overall incidence of complications ranged from 0% to 32.3% of knees. Failure ranged from 0% to 10.7% of knees, whereas patellar fractures occurred in 0% to 8.3% of knees, primarily in patients treated with full-length transverse tunnel or 2-tunnel techniques. All patellar fractures occurred in patients with patellar tunnels ranging from 4.5 to 6.0 mm in diameter. The incidence of postoperative knee stiffness/range of motion deficit ranged from 0% to 20%. Persistent anterior knee pain, ranged from 0% to 32.3%. CONCLUSIONS: Complications following primary MPFL reconstruction ranged from 0% to 32.3% of knees, primarily consisting of residual anterior knee pain. Failure ranged from 0% to 10.7% of knees, whereas patellar fractures were reported in 0% to 8.3% of knees. Fractures primarily occurred with a full-length transverse tunnel or 2-tunnel techniques, whereas all fractures occurred with patellar tunnels ranging from 4.5 mm to 6.0 mm in diameter. LEVEL OF EVIDENCE: IV; Systematic Review of Level I-IV studies.

Effects of Purinergic Receptor Deletion or Pharmacologic Modulation on Pulmonary Inflammation in Mice.

COVID-19 disease is associated with progressive accumulation of SARS-CoV-2-specific mRNA, which is recognized by innate immune receptors, such as TLR3. This in turn leads to dysregulated production of multiple cytokines, including IL-6, IFN-γ, CXCL1, and TNF-α. Excessive production of these cytokines leads to acute lung injury (ALI), which consequently compromises alveolar exchange of O2 and CO2. It is therefore of considerable interest to develop novel therapies that reduce pulmonary inflammation and stem production of pro-inflammatory cytokines, potentially for COVID-19 patients that are at high risk of developing severe disease. Purinergic signaling has a central role in fine-tuning the innate immune system, with P2 (nucleotide) receptor antagonists and adenosine receptor agonists having anti-inflammatory effects. Accordingly, we focused here on the potential role of purinergic receptors in driving neutrophilic inflammation and cytokine production in a mouse model of pulmonary inflammation. To mimic the effects of SARS-CoV-2-specific RNA accumulation in mice, we administered progressively increasing daily doses of a viral mimetic, polyinosinic:polycytidylic acid [poly(I:C)] into the airways of mice over the course of 1 week. Some mice also received increasing daily doses of ovalbumin to mimic virus-encoded protein accumulation. Animals receiving both poly(I:C) and ovalbumin displayed particularly high cytokine levels and neutrophilia, suggestive of both innate and antigen-specific, adaptive immune responses. The extent of these responses was diminished by genetic deletion (P2Y14R, P2X7R) or pharmacologic modulation (P2Y14R antagonists, A3AR agonists) of purinergic receptors. These results suggest that pharmacologic modulation of select purinergic receptors might be therapeutically useful in treating COVID-19 and other pulmonary infections.

Synthesis and pharmacological characterization of multiply substituted 2H-chromene derivatives as P2Y6 receptor antagonists.

P2Y6 receptor (P2Y6R) antagonists represent potential drugs for treating cancer, pain, neurodegeneration, asthma, diabetes, colitis and other disorders. However, there are few chemical classes of known competitive antagonists. We recently explored the structure activity relationship (SAR) of 2H-chromene derivatives as P2Y6R antagonists of moderate affinity. New analogues in this series modified at five positions were synthesized and shown to antagonize Ca2+ transients induced by the native agonist UDP in human (h) P2Y6R-expressing (but not turkey P2Y1R-, hP2Y2R- or hP2Y4R-expressing) astrocytoma cells. Alternatives to the reported 2-(trifluoromethyl)- and 3-nitro- substitutions of this scaffold were not identified. However, 6­fluoro 11 and 6­chloro 12 analogues displayed enhanced potency compared to other halogens, although still in the 1 - 2 µM range. Similar halogen substitution at 5, 7 or 8 positions reduced affinity. 5- or 8­Triethylsilylethynyl extension maintained hP2Y6R affinity, with IC50 0.46 µM for 26 (MRS4853). The 6,8­difluoro analogue 27 (IC50 2.99 µM) lacked off-target activities among 45 sites examined, unlike earlier analogues that bound to biogenic amine receptors. 11 displayed only one weak off-target activity (σ2). Mouse P2Y6R IC50s of 5, 25, 26 and 27 were 4.94, 17.6, 6.15 and 17.8 µM, respectively, but most other analogues had reduced affinity (>20 µM) compared to the hP2Y6R. These analogues are suitable for evaluation in in vivo inflammation and cancer models, which will be performed in the future studies.

Therapeutic Potential of Tuna Backbone Peptide and Its Analogs: An In Vitro and In Silico Study.

Tuna backbone peptide (TBP) has been reported to exert potent inhibitory activity against lipid peroxidation in vitro. Since this bears relevant physiological implications, this study was undertaken to assess the impact of peptide modifications on its bioactivity and other therapeutic potential using in vitro and in silico approach. Some TBP analogs, despite lower purity than the parent peptide, exerted promising antioxidant activities in vitro demonstrated by ABTS radical scavenging assay and cellular antioxidant activity assay. In silico digestion of the peptides resulted in the generation of antioxidant, angiotensin-converting enzyme (ACE), and dipeptidyl peptidase-IV (DPPIV) inhibitory dipeptides. Using bioinformatics platforms, we found five stable TBP analogs that hold therapeutic potential with their predicted multifunctionality, stability, non-toxicity, and low bitterness intensity. This work shows how screening and prospecting for bioactive peptides can be improved with the use of in vitro and in silico approaches.

Structure activity relationship of 3-nitro-2-(trifluoromethyl)-2H-chromene derivatives as P2Y6 receptor antagonists.

Various 6-alkynyl analogues of a known 3-nitro-2-(trifluoromethyl)-2H-chromene antagonist 3 of the Gq-coupled P2Y6 receptor (P2Y6R) were synthesized using a Sonogashira reaction to replace a 6-iodo group. The analogues were tested in a functional assay consisting of inhibition of calcium mobilization in P2Y6R-expressing astrocytoma cells elicited by native P2Y6R agonist UDP. 6-Ethynyl and 6-cyano groups were installed, and the alkynes were extended through both alkyl and aryl spacers. The most potent antagonists, with IC50 of ~1 µM, were found to be trialkylsilyl-ethynyl 7 and 8 (3-5 fold greater affinity than reference 3), t-butyl prop-2-yn-1-ylcarbamate 14 and p-carboxyphenyl-ethynyl 16 derivatives, and 3 and 8 displayed surmountable antagonism of UDP-induced production of inositol phosphates. Other chain-extended terminal carboxylate derivatives were less potent than the corresponding methyl ester derivatives. Thus, the 6 position in this chromene series is suitable for derivatization with flexibility of substitution, even with sterically extended chains, without losing P2Y6R affinity. However, a 3-carboxylic acid or 3-ester substitution did not serve as a nitro bioisostere, as the affinity was eliminated. These compounds provide additional ligand tools for the underexplored P2Y6R, which is a target for inflammatory, neurodegenerative and metabolic diseases.

Near-infrared laser thermal conjunctivoplasty.

Conjunctivochalasis is a common cause of tear dysfunction due to the conjunctiva becoming loose and wrinkly with age. The current solutions to this disease include either surgical excision in the operating room, or thermoreduction of the loose tissue with hot wire in the clinic. We developed a near-infrared laser thermal conjunctivoplasty system. The system utilizes a 1460-nm programmable laser diode system as the light source. At this wavelength, a water absorption peak exists and the blood absorption is minimal, so the heating of redundant conjunctiva is even and there is no bleeding. A miniaturized handheld probe delivers the laser light and reshapes the laser into a 10 × 1 mm2 line on the working plane. A foot pedal is used to deliver a preset number of calibrated laser pulses. A fold of loose conjunctiva is grasped by a pair of forceps. The NIR laser light is delivered through an optical fiber and a laser line is aimed exactly on the conjunctival fold by a cylindrical lens. Ex vivo experiments using porcine eye was performed to investigate the induced shrinkage of conjunctiva and decide the optimal laser parameters. It was found that up to 45% of conjunctiva shrinkage could be achieved.