The cadaveric studies and the definition of the antero-lateral ligament of the knee: From the anatomical features to the patient-specific reconstruction surgical techniques

Cadaver studies represented a milestone in surgical orthopaedic research, and still today they play a crucial role in the achievement of new knowledge about joint disease behaviour and treatment. In this review, an overview of the cadaver studies available in the literature about the anatomy, role, and treatment of the antero-lateral ligament (ALL) of the knee was performed. The aim of the review was to describe and gain more insight into the part of in vitro study in understanding knee joint anatomy and biomechanics, and in developing surgical reconstruction techniques. The findings of the review showed that cadaver studies had, and will continue to have, a key role in the research of knee joint biomechanics and surgical reconstruction. Moreover, they represent a powerful tool to develop and test new devices which could be useful in clinical and surgical practice

Severe bicompartmental bone bruise is associated with rotatory instability in anterior cruciate ligament injury

Purpose: The presence and severity of bone bruise is more and more investigated in the non-contact anterior cruciate ligament (ACL) injury context. Recent studies have advocated a correlation between bone bruise and preoperative knee laxity. The aim of the present study was to investigate the correlation between bone bruise and preoperative rotatory knee laxity. Methods: Twenty-nine patients (29.1 ± 9.8 years) with MRI images at a maximum of 3 months after ACL injury (1.6 ± 0.8 months) were included. The bone bruise severity was evaluated according to the International Cartilage Repair Society (ICRS) scale for lateral femoral condyle, lateral tibial plateau, medial femoral condyle, and medial tibial plateau. The intraoperative rotational knee laxity was evaluated through a surgical navigation system in terms of internal–external rotation at 30° and 90° of knee flexion (IE30, IE90) and internal–external rotation and acceleration during pivot-shift test (PS IE, PS ACC). The KOOS score was also collected. The association between ICRS grade of bone bruise and rotational laxity or KOOS was investigated. Results: Significant correlation (p < 0.05) was found between the bone bruise severity on the medial tibial plateau and rotational laxity (IE90, PS IE, and PS ACC) and between the severity of bone bruise on femoral lateral condyle and KOOS-Symptoms sub-score. The presence of bone bruise on the medial tibial plateau was significantly associated with a lateral femoral notch sign > 2 mm (very strong odds ratio). No kinematical differences were found between none-to-deep and extensive-generalized lateral bone bruise, while higher IE30 and IE90 were found in extensive-generalized bicompartmental bone bruise than isolated extensive-generalized lateral bone bruise. Conclusion: A severe bicompartmental bone bruise was related to higher rotatory instability in the intraoperative evaluation of ACL deficient knees. The severity of edema on the medial tibial plateau was directly correlated with higher intraoperative pivot shift, and the size of edema on the lateral femoral condyle was associated with lower preoperative clinical scores. Level of evidence: Level II

Minimum 10-Year Clinical Outcome of Lateral Collagen Meniscal Implants for the Replacement of Partial Lateral Meniscal Defects: Further Results From a Prospective Multicenter Study

Background: The collagen meniscal implant (CMI) is a biologic scaffold aimed at replacing partial meniscal defects. The long-term results of lateral meniscal replacement have never been investigated. Purpose: To document the clinical outcomes and failures of lateral CMI implantation for partial lateral meniscal defect at a minimum 10-year follow-up. Study Design: Case series; Level of evidence, 4, Methods: This study included 24 consecutive patients who underwent lateral CMI implantation for partial lateral meniscal defects between April 2006 and September 2009 and who were part of a previous study with a 2-year follow-up. Outcome measures at the latest follow-up included the Lysholm score, Knee injury and Osteoarthritis Outcome Score, visual analog scale (VAS) for pain, Tegner activity level, and EuroQol 5-Dimensions score. Data regarding complications and failures were collected, and patients were asked about their satisfaction with the procedure. Results: Included in the final analysis were 19 patients (16 male, 3 female) with a mean age at surgery of 37.1 ± 12.6 years and a mean follow-up of 12.4 ± 1.5 years (range, 10-14 years). Five failures (26%) were reported: 1 CMI removal because of implant breakage and 4 joint replacements (2 unicompartmental knee arthroplasties and 2 total knee arthroplasties). The implant survival rate was 96% at 2 years, 85% at 5 years, 85% at 10 years, 77% at 12 years, and 64% at 14 years. Lysholm scores at the final follow-up were rated as “excellent” in 36% (5 of 14 nonfailures), “good” in 43% (6 of 14), and “fair” in 21% (3 of 14). The VAS score was 3.1 ± 3.1, with only 16% (3 of 19 patients) reporting that they were pain-free; the median Tegner score was 3 (interquartile range, 2-5). All clinical scores decreased from the 2-year follow-up; however, with the exception of the Tegner score, they remained significantly higher compared with the preoperative status. Overall, 79% of patients were willing to undergo the same procedure. Conclusion: Lateral CMI implantation for partial lateral meniscal defects provided good long-term results, with a 10-year survival rate of 85% and a 14-year survival rate of 64%. At the final follow-up, 58% of the patients had “good” or “excellent” Lysholm scores. However, there was a general decrease in outcome scores between the short- and the long-term follow-up

Do Clinical Outcomes and Failure Rates Differ in Patients With Combined ACL and Grade 2 MCL Tears Versus Isolated ACL Tears?: A Prospective Study With 14-Year Follow-up

Background: A combined injury to the anterior cruciate ligament (ACL) and medial collateral ligament (MCL) is a common injury pattern encountered during clinical practice. Recent systematic reviews have found no consensus on the optimal method of managing this combined ligament injury pattern, and no long-term studies with modern techniques are available in the literature. Purpose: To compare 2 groups of patients who underwent isolated ACL reconstruction in terms of failures and clinical scores at long-term follow-up. In the first group were patients with isolated ACL tears (ACL group), while the second was composed of patients with combined ACL and MCL grade 2 tears (ACL + MCL group). Study Design: Cohort study; Level of evidence, 3. Methods: A total of 57 patients (37 in the ACL group and 20 in the ACL + MCL group) underwent isolated ACL reconstruction with a double-bundle technique between January and December 2005. Patients were contacted for scores on the International Knee Documentation Committee subjective form, Western Ontario and McMaster Universities Osteoarthritis Index, and Tegner activity scale as well as data regarding ipsilateral or contralateral revision ACL surgery. A 2-way analysis of variance for repeated measures was used to statistically assess the differences between the groups. Results: Overall, 49 patients (86%) completed the survey and were therefore included in the study. The minimum follow-up was 14.6 years (range, 14.1-15.2 years). There was a significant reduction in both groups of all the outcome scores between the intermediate and final-follow-up. The number of failures was 3 of 31 (9.7%) in the ACL group and 1 of 18 (5.5%) in the ACL + MCL group; this difference was not significant. Moreover, there were no clinical differences between the groups in terms of graft failures, contralateral lesions, and clinical scores. Conclusion: At 14-year follow-up, no clinical difference or increased failure rate was observed between the study groups, suggesting that isolated ACL reconstruction could represent an appropriate treatment for a combined ACL and MCL grade 2 lesion

Satisfactory clinical results and low failure rate of medial collagen meniscus implant (CMI) at a minimum 20 years of follow-up

Purpose: The aim of the study was to evaluate the long-term clinical results, reoperations, surgical failure and complications at a minimum of 20 year of follow-up of the first 8 medial CMI scaffolds implanted by a single surgeon during a pilot European Prospective study. Methods: Seven (88%) out of 8 patients were contacted. The Cincinnati Score, VAS, and Lysholm score were collected. Moreover, magnetic resonance imaging (MRI) was performed on 4 patients at the last follow-up. Complications, reoperations and failures were also investigated. Results: The average follow-up was 21.5 ± 0.5 years. One patient underwent TKA after 13 years from CMI implantation; a second patient underwent valgus high tibial osteotomy 8 years after the index surgery and another patient underwent anterior cruciate ligament hardware removal at 21 years of follow-up. At the final follow-up, 3 patients were rated as “Excellent”, 1 as “Good” and 2 as “Fair” according to the Lysholm score. The Cincinnati score and the VAS were substantially stable over time. The MRI showed a mild osteoarthritis progression in 3 out of 4 patients according to the Yulish score, and the CMI signal was similar to the mid-term follow-up revealing 3 cases of myxoid degeneration and 1 case of normal signal with reduced scaffold size. Conclusion: The medial CMI is a safe procedure: satisfactory clinical results and a low failure rate could be expected even at a long-term follow-up. For this purpose, the correct indication as well as correcting axial malalignment and addressing knee instability at the time of the index surgery is mandatory. On the other hand, a mild osteoarthritis progression could be expected even after meniscus replacement. Level of evidence: IV

Knee position at the moment of bone bruise could reflect the late phase of non-contact anterior cruciate ligament injury rather than the mechanisms leading to ligament failure

Purpose: The aim of the present study was to trace knee position at the time of bone bruise (BB) and investigate how much this position departed from the knee biomechanics of an in vivo flexion–extension. Methods: From an original cohort of 62 patients, seven (11%) presented bicompartmental edemas and were included in the study. 3D models of bones and BB were obtained from MRI. Matching bone edemas, a reconstruction of the knee at the moment of BB was obtained. For the same patients, knee kinematics of a squat was calculated using dynamic Roentgen sterephotogrammetric analysis (RSA). Data describing knee position at the moment of BB were compared to kinematics of the same knee extrapolated from RSA system. Results: Knee positions at the moment of BB was significantly different from the kinematics of the squat. In particular, all the patients’ positions were out of squat range for both anterior and proximal tibial translation, varus–valgus rotation (five in valgus and two in varus), tibial internal–external rotation (all but one, five externally and one internally). A direct comparison at same flexion angle between knee at the moment of BB (average 46.1° ± 3.8°) and knee during squat confirmed that tibia in the former was significantly more anterior (p < 0.0001), more externally rotated (6.1 ± 3.7°, p = 0.04), and valgus (4.1 ± 2.4°, p = 0.03). Conclusion: Knee position at the moment of Bone bruise position was out of physiological in-vivo knee range of motion and could reflect a locked anterior subluxation occurring in the late phase of ACL injury rather than the mechanism leading to ligament failure. Level of evidence: Level I

New miniPromoter Ple345 (NEFL) drives strong and specific expression in retinal ganglion cells of mouse and primate retina.

Retinal gene therapy is leading the neurological gene therapy field, with 32 ongoing clinical trials of recombinant adeno-associated virus (rAAV)-based therapies. Importantly, over 50% of those trials are using restricted promoters from human genes. Promoters that restrict expression have demonstrated increased efficacy and can limit the therapeutic to the target cells thereby reducing unwanted off-target effects. Retinal ganglion cells are a critical target in ocular gene therapy; they are involved in common diseases such as glaucoma, rare diseases such as Leber's hereditary optic neuropathy, and in revolutionary optogenetic treatments. Here, we used computational biology and mined the human genome for the best genes from which to develop a novel minimal promoter element(s) designed for expression in restricted cell types (MiniPromoter) to improve the safety and efficacy of retinal ganglion cell gene therapy. Gene selection included the use of the first available droplet-based single-cell RNA sequencing (Drop-seq) dataset, and promoter design was bioinformatically driven and informed by a wide range of genomics datasets. We tested seven promoter designs from four genes in rAAV for specificity and quantified expression strength in retinal ganglion cells in mouse, and then the single best in nonhuman primate retina. Thus, we developed a new human-DNA MiniPromoter, Ple345 (NEFL), which in combination with intravitreal delivery in rAAV9 showed specific and robust expression in the retinal ganglion cells of the nonhuman-primate rhesus macaque retina. In mouse, we also developed MiniPromoters expressing in retinal ganglion cells, the hippocampus of the brain, a pan neuronal pattern in the brain, and peripheral nerves. As single-cell transcriptomics such as Drop-seq become available for other cell types, many new opportunities for additional novel restricted MiniPromoters will present

-Dual nucleoside therapy for HIV infection: analysis of results and factors influencing viral response and long term efficacy.

We performed a retrospective analysis of our experience with dual nucleoside regimens to look for predictors of long term benefit. We evaluated a cohort of 68 HIV-infected patients treated at 3 Italian hospital-based facilities. The results were analysed using univariate and multivariate statistical analyses. Fourty-three males and 25 females were treated for 22 ± 14 months. Sixty three patients (92.6%) suffered no or low-grade side-effects. Thirty-four patients (50 %) reached a viral load 150/μl pre-treatment viremia 1,500/μl, and no previous exposure to NRTI. Total lymphocyte counts and CD4+ T-cells showed a significant correlation. Dual NRTI regimens may be still considered for patients unable to tolerate HAART regimens and presenting with favourable predictors of response

Predictors of pain intensity and persistence in a prospective Italian cohort of patients with herpes zoster: relevance of smoking, trauma and antiviral therapy

Herpes zoster (HZ) is a common disease, characterized by rash-associated localized pain. Its main complication, post-herpetic neuralgia (PHN), is difficult to treat and may last for months to years in the wake of rash resolution. Uncertainties remain as to the knowledge of predictors of HZ-related pain, including the role of antiviral therapy in preventing PHN in ordinary clinical practice. This prospective cohort study was aimed at investigating pain intensity at HZ presentation and its correlates, as well as the incidence of PHN and its predictors

A Lateral Extra-articular Procedure Reduces the Failure Rate of Revision Anterior Cruciate Ligament Reconstruction Surgery Without Increasing Complications: A Systematic Review and Meta-analysis

Background: Lateral extra-articular procedures are becoming increasingly popular in association with anterior cruciate ligament (ACL) reconstruction, especially in patients with persistent rotatory instability and in a high-risk population. However, few studies have investigated the outcomes of the lateral extra-articular procedure as an associated procedure in an ACL revision (R-ACLR) setting and its benefit with respect to isolated intra-articular reconstruction. Hypothesis: Lateral extra-articular procedures reduce the failure rate of revision ACL reconstruction (R-ACLR). Purpose: To compare subjective outcomes, knee stability, and failure and complication rates between patients who underwent ACL revision with and without an associated lateral extra-articular procedure. Study design: Systematic review and meta-analysis; Level of evidence, 3. Methods: A systematic search of the PubMed, Cochrane, and OVID databases was performed on September 2022 in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Eligible studies were trials directly comparing patients who had isolated ACL revision with patients who had ACL revision associated with lateral extra-articular procedures at a minimum follow-up of 2 years. A meta-analysis was performed, and bias and the quality of the evidence were rated according to the Newcastle-Ottawa Scale. The meta-analysis was conducted according to the PRISMA guidelines. Results: Eight studies were included: a total of 334 patients were treated with isolated revision (isolated (R-ACLR)) and 342 treated with combined revision and a lateral extra-articular procedure (combined (R-ACLR)). For the failure rate, the meta-analysis showed a significantly decreased relative risk reduction of 54% (P = .004) in patients with combined (R-ACLR) with respect to isolated R-ACL, whereas no difference in complication rate was observed. The combined (R-ACLR) group demonstrated a decreased risk ratio of 50% (P = .002) for having a positive pivot-shift test result and a relative risk reduction of 68% (P = .003) for having a grade 2-3 pivot shift when compared with the isolated (R-ACLR) group. Finally, no significant differences were observed among the lateral extra-articular procedures. Conclusion: The addition of a lateral extra-articular procedure to revision ACL significantly reduced the failure rate and postoperative pivot shift without increasing the complication rate. Anterolateral ligament reconstruction and a lateral extra-articular procedure with iliotibial band were effective in improving the outcomes of revision ACL reconstruction. Further high-level studies could help to clarify which subgroup of patients could particularly benefit from an anterolateral procedure in the context of ACL revision