Double-bundle ACL combined with ALL reconstruction for patients at high risk of ACL failure: clinical and radiological results.

BACKGROUND: We investigated whether double-bundle (DB) anterior cruciate ligament (ACL) reconstruction (ACLR) combined with anterolateral ligament reconstruction (ALLR) improved clinical and radiological outcomes in patients at high risk of ACL failure. The primary outcome was graft failure, and secondary outcomes included knee stability and patient-reported outcome measures (PROMs). PATIENTS AND METHODS: Fifty-two patients who underwent DB ACLR combined with ALLR were included in this retrospective cohort study. Preoperative risk factors, including femorotibial angle (FTA), lateral tibial slope (LTS), medial tibial slope (MTS), and meniscal tears, were assessed using X-ray and magnetic resonance imaging (MRI). The grade of post-operative pivot shift, Lysholm score, and Tegner activity score were used to assess clinical outcomes. The minimum follow up duration was 2 years. RESULTS: The cohort (mean age, 26.1 ± 9.4 years; 51.9% male) had a mean follow-up duration of 28.9 ± 3.4 months. Preoperatively, 57.8% had lateral meniscus (LM) tears, and 61.0% had a grade 2-3 pivot shift. Postoperatively, no graft failures or revision cases occurred during follow-up. Approximately 90.4% of the patients exhibited a negative pivot shift (p < 0.001), with Lysholm and Tegner activity scores of 92.5 ± 6.1 and 5.1 ± 2.0. The medial meniscus (MM) tear group had a significantly smaller FTA than the intact group (p = 0.043). No significant differences in PROMs were found between the LM tear and intact LM groups or between the high and low MTS or LTS groups (p = n.s.). CONCLUSION: DB ACLR combined with ALLR had satisfactory clinical outcomes in patients at high risk of ACL failure, with no graft failures observed during a mean follow-up duration of 2.4 years. The technique effectively reduced the postoperative pivot shift, regardless of preoperative risk factors. STUDY DESIGN: Level IV, retrospective therapeutic case-series. TRAIL REGISTRATION: ethical approval number, 202300134B0; ethical committee, the Institutional Review Board of Chang Gung Medical Foundation.

Failure of the linkage mechanism in a semi-constrained total elbow arthroplasty is a rare and unpredictable event: a review of seven cases.

PURPOSE: Linked component of total elbow arthroplasty (TEA) consisted of bushing and locking pins. Failure of linked components is a rare complication of TEA. This study aims to investigate the mechanism and consequence of failure of the linkage mechanism in TEA surgeries. METHODS: Between 2010 and 2021, five patients received revision operation due to linked component failure. Besides, two patients underwent primary operation at another institute were also analyzed due to failure of the linkage mechanism. RESULTS: All seven patients underwent primary TEA and mean age for primary TEA was 48 (range, 27-62). Two patients had TEA for post-traumatic arthritis, three patients for rheumatoid arthritis, and two patients for comminuted distal humerus fracture. The average time between primary TEA and revision TEA for linked component failure was 13.6 years. Three bushing wear and four locking pin dissociation were diagnosed according to pre-operative radiography. Elbow pain and swelling are the most common clinical symptoms. Severe osteolysis, periprosthetic fracture, and stem loosening were noted in three bushing wear cases. In four dissociation of locking pin cases, breakage of male locking pin phalanges was demonstrated in two patients. For revision procedures, both the locking pins and bushings were replaced. No patients in the study required additional surgery after the revision operation for linked component failure. CONCLUSION: Osteolysis, component loosening, periprosthetic fracture may be expected after linked component failure. Patients should be regularly followed up from short-term to long-term with radiography. Early diagnosis and intervention with linked component exchange can prevent extensive revision surgery.

Early versus delayed mobilization for arthroscopic rotator cuff repair (small to large sized tear): a meta-analysis of randomized controlled trials.

BACKGROUND: The timing to start passive or active range of motion (ROM) after arthroscopic rotator cuff repair remains unclear. This systematic review and meta-analysis evaluated early versus delayed passive and active ROM protocols following arthroscopic rotator cuff repair. The aim of this study is to systematically review the literature on the outcomes of early active/passive versus delayed active/passive postoperative arthroscopic rotator cuff repair rehabilitation protocols. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) published up to April 2022 comparing early motion (EM) versus delayed motion (DM) rehabilitation protocols after arthroscopic rotator cuff repair for partial and full-thickness tear was conducted. The primary outcome was range of motion (anterior flexion, external rotation, internal rotation, abduction) and the secondary outcomes were Constant-Murley score (CMS), Simple Shoulder Test Score (SST score) and Visual Analogue Scale (VAS). RESULTS: Thirteen RCTs with 1,082 patients were included in this study (7 RCTs for early passive motion (EPM) vs. delayed passive motion (DPM) and 7 RCTs for early active motion (EAM) vs. delayed active motion (DAM). Anterior flexion (1.40, 95% confidence interval (CI), 0.55-2.25) and abduction (2.73, 95%CI, 0.74-4.71) were higher in the EPM group compared to DPM. Similarly, EAM showed superiority in anterior flexion (1.57, 95%CI, 0.62-2.52) and external rotation (1.59, 95%CI, 0.36-2.82), compared to DAM. There was no difference between EPM and DPM for external rotation, retear rate, CMS and SST scores. There was no difference between EAM and DAM for retear rate, abduction, CMS and VAS. CONCLUSION: EAM and EPM were both associated with superior ROM compared to the DAM and DPM protocols. EAM and EPM were both safe and beneficial to improve ROM after arthroscopic surgery for the patients with small to large sized tears.

Analysis of Cellular Crosstalk and Molecular Signal between Periosteum-Derived Precursor Cells and Peripheral Cells During Bone Healing Process Using a Paper-Based Osteogenesis-On-A-Chip Platform.

Periosteum-derived progenitor cells (PDPCs) are highly promising cell sources that are indispensable in the bone healing process. Adipose-derived stem cells (ADSCs) are physiologically close to periosteum tissue and release multiple growth factors to promote the bone healing process. Co-culturing PDPCs and ADSCs can construct periosteum-bone tissue microenvironments for the study of cellular crosstalk and molecular signal in the bone healing process. In the current work, a paper-based osteogenesis-on-a-chip platform was successfully developed to provide an in vitro three-dimensional coculture model. The platform was a paper substrate sandwiched between PDPC-hydrogel and ADSC-hydrogel suspensions. Cell secretion could be transferred through the paper substrate from one side to another side. Growth factors including BMP2, TGF-ß, POSTN, Wnt proteins, PDGFA, and VEGFA were directly analyzed by a paper-based immunoassay. Cellular crosstalk was studied by protein expression on the paper substrate. Moreover, osteogenesis of PDPCs was investigated by examining the mRNA expressions of PDPCs after culture. Neutralizing and competitive assays were conducted to understand the correlation between growth factors secreted from ADSCs and the osteogenesis of PDPCs. In vitro periosteum-bone tissue microenvironment was established by the paper-based osteogenesis-on-a-chip platform. The proposed approach provides a promising assay of cellular crosstalk and molecular signal in 3D coculture microenvironment that may potentially lead to the development of effective bone regeneration therapy.

Using Single Peroneal Longus Tendon Graft for Segmental Meniscus Transplantation and Revision Anterior Cruciate Ligament Combined Anterolateral Reconstruction.

This case report describes a new approach to segmental meniscal reconstruction using a peroneal longus autograft in a patient with recurrent traumatic medial meniscus tear and anterior cruciate ligament reconstruction (ACLR) failure. While allograft meniscal transplantation is the preferred method for treating meniscal deficiency, its high cost and various legal regulations have limited its widespread use. Autologous tendon grafts have been proposed as a substitute for allograft meniscus transplantation, but their initial results were poor, leading to little progress in this area. However, recent animal experiments and clinical studies have demonstrated promising results in using autologous tendon grafts for meniscal transplantation, including improvements in pain and quality of life for patients. Further research is needed to evaluate the effectiveness of segmental meniscal reconstruction using autologous tendon grafts, but it could potentially lead to more accessible and cost-effective treatment options for patients with meniscal deficiency.

Robotic versus laparoscopic hepatectomy: A single-center, propensity score- matched study.

BACKGROUND: Although the effectiveness of robotic hepatectomy (RH) has been evaluated in several studies, the superiority of RH over other approaches has not been definitely established. Therefore, in the present propensity score-matched cohort study, we compared RH and laparoscopic hepatectomy (LH) in terms of perioperative and oncologic outcomes. METHODS: This retrospective study included patients who underwent RH or LH for benign and malignant liver lesions at a single center in Taiwan at any time between 2014 and 2020. Confounding factors, specifically age, sex, body mass index, American Society of Anesthesiologists score, IWATE criteria, and Charlson comorbidity index, were adjusted through propensity score matching (PSM). RESULTS: A total of 329 patients were finally included in this study. Two homogeneous groups (RH and LH; n, 72 each) were formed using PSM. The RH group had a longer operative time (median: 231 vs.180 min, respectively; P = .001) and lower conversion (to open surgery) rate (9.7% vs.0.0%, respectively; P = .013) than did the LH group. However, the two groups did not differ in terms of other perioperative outcomes, specifically blood loss, hospital stay, intensive care unit admission, mortality, morbidity, or tumor margin status. CONCLUSIONS: The rate of conversion to open surgery is lower in RH than in LH. Although operative time is longer in RH than in LH, RH is feasible and safe for patients with benign or malignant liver lesion. Our study also demonstrated comparable oncological results in patients with hepatocellular carcinoma between LH and RH group.

Galectin-1-mediated MET/AXL signaling enhances sorafenib resistance in hepatocellular carcinoma by escaping ferroptosis.

Sorafenib, a small-molecule inhibitor targeting several tyrosine kinase pathways, is the standard treatment for advanced hepatocellular carcinoma (HCC). However, not all patients with HCC respond well to sorafenib, and 30% of patients develop resistance to sorafenib after short-term treatment. Galectin-1 modulates cell-cell and cell-matrix interactions and plays a crucial role in HCC progression. However, whether Galectin-1 regulates receptor tyrosine kinases by sensitizing HCC to sorafenib remains unclear. Herein, we established a sorafenib-resistant HCC cell line (Huh-7/SR) and determined that Galectin-1 expression was significantly higher in Huh-7/SR cells than in parent cells. Galectin-1 knockdown reduced sorafenib resistance in Huh-7/SR cells, whereas Galectin-1 overexpression in Huh-7 cells increased sorafenib resistance. Galectin-1 regulated ferroptosis by inhibiting excessive lipid peroxidation, protecting sorafenib-resistant HCC cells from sorafenib-mediated ferroptosis. Galectin-1 expression was positively correlated with poor prognostic outcomes for HCC patients. Galectin-1 overexpression promoted the phosphorylation of AXL receptor tyrosine kinase (AXL) and MET proto-oncogene, receptor tyrosine kinase (MET) signaling, which increased sorafenib resistance. MET and AXL were highly expressed in patients with HCC, and AXL expression was positively correlated with Galectin-1 expression. These findings indicate that Galectin-1 regulates sorafenib resistance in HCC cells through AXL and MET signaling. Consequently, Galectin-1 is a promising therapeutic target for reducing sorafenib resistance and sorafenib-mediated ferroptosis in patients with HCC.

Machine Learning Algorithm Detection of Confluent B-Lines.

OBJECTIVE: B-lines are a ring-down artifact of lung ultrasound that arise with increased alveolar water in conditions such as pulmonary edema and infectious pneumonitis. Confluent B-line presence may signify a different level of pathology compared with single B-lines. Existing algorithms aimed at B-line counting do not distinguish between single and confluent B-lines. The objective of this study was to test a machine learning algorithm for confluent B-line identification. METHODS: This study used a subset of 416 clips from 157 subjects, previously acquired in a prospective study enrolling adults with shortness of breath at two academic medical centers, using a hand-held tablet and a 14-zone protocol. After exclusions, random sampling generated a total of 416 clips (146 curvilinear, 150 sector and 120 linear) for review. A group of five experts in point-of-care ultrasound blindly evaluated the clips for presence/absence of confluent B-lines. Ground truth was defined as majority agreement among the experts and used for comparison with the algorithm. RESULTS: Confluent B-lines were present in 206 of 416 clips (49.5%). Sensitivity and specificity of confluent B-line detection by algorithm compared with expert determination were 83% (95% confidence interval [CI]: 0.77-0.88) and 92% (95% CI: 0.88-0.96). Sensitivity and specificity did not statistically differ between transducers. Agreement between algorithm and expert for confluent B-lines measured by unweighted κ was 0.75 (95% CI: 0.69-0.81) for the overall set. CONCLUSION: The confluent B-line detection algorithm had high sensitivity and specificity for detection of confluent B-lines in lung ultrasound point-of-care clips, compared with expert determination.

Radiographic Analysis in Extra-Articular and Intra-Articular Distal Radius Fractures Treated with Variable-Angle Volar Locking Plate Fixation.

(1) Background: Different distal radial fracture types have different prognosis after fixation. Our study aim is to evaluate the differences in radiographic parameters by using variable-angle volar locking plate (VAVLP) fixation according to extra-articular and intra-articular distal radial fracture. (2) Methods: There are two groups: extra-articular group (21) and intra-articular group (25). Forearm radiographs immediately after surgery and at 3 months after operation were reviewed for analyzing radial height (RH), ulnar variance (UV), radial inclination (RI), volar tilt (VT), tear drop angle (TDA), distal dorsal cortical distance (DDD), and Soong classification (SC). (3) Results: There were no significant differences in the above parameters between two groups at either immediately post-operative or at 3-month follow-up, except for TDA (p = 0.048). Most patients in both groups were at low risk of flexor tendon rupture, except for two cases. We observed a positive correlation between post-operative DDD and 3-month change in the intra-articular group, but not the extra-articular group. (4) Conclusions: Our study demonstrates that VAVLP fixation is effective in maintaining the stability of most radiographic parameters and reduces the risk of tendon rupture in both extra-articular and intra-articular distal radial fractures. Post-operative DDD can be used to predict the degree of subsequent displacement in patients with intra-articular fractures fixed with VAVLP.

Two- Versus 8-Zone Lung Ultrasound in Heart Failure: Analysis of a Large Data Set Using a Deep Learning Algorithm.

OBJECTIVE: Scanning protocols for lung ultrasound often include 8 or more lung zones, which may limit real-world clinical use. We sought to compare a 2-zone, anterior-superior thoracic ultrasound protocol for B-line artifact detection with an 8-zone approach in patients with known or suspected heart failure using a deep learning (DL) algorithm. METHODS: Adult patients with suspected heart failure and B-lines on initial lung ultrasound were enrolled in a prospective observational study. Subjects received daily ultrasounds with a hand-held ultrasound system using an 8-zone protocol (right and left anterior/lateral and superior/inferior). A previously published deep learning algorithm that rates severity of B-lines on a 0-4 scale was adapted for use on hand-held ultrasound full video loops. Average severities for 8 and 2 zones were calculated utilizing DL ratings. Bland-Altman plot analyses were used to assess agreement and identify bias between 2- and 8-zone scores for both primary (all patients, 5728 videos, 205 subjects) and subgroup (confirmed diagnosis of heart failure or pulmonary edema, 4464 videos, 147 subjects) analyses. RESULTS: Bland-Altman plot analyses revealed excellent agreement for both primary and subgroup analyses. The absolute difference on the 4-point scale between 8- and 2-zone average scores was not significant for the primary dataset (0.03; 95% CI -0.01 to 0.07) or the subgroup (0.01; 95% CI -0.04 to 0.06). CONCLUSION: Utilization of a 2-zone, anterior-superior thoracic ultrasound protocol provided similar severity information to an 8-zone approach for a dataset of subjects with known or suspected heart failure.

Identification of Safe and Effective Intravenous Dose of AAVrh.10hFXN to Treat the Cardiac Manifestations of Friedreich's Ataxia.

Friedreich's ataxia (FA) is a life-threatening autosomal recessive disorder characterized by neurological and cardiac dysfunction. Arrhythmias and heart failure are the main cause of premature death. From prior studies in murine models of FA, adeno-associated virus encoding the normal human frataxin gene (AAVrh.10hFXN) effectively treated the cardiac manifestations of the disease. However, the therapeutic dose window is limited by high level of human frataxin (hFXN) gene expression associated with toxicity. As a therapeutic goal, since FA heterozygotes have no clinical manifestations of FA, we estimated the level of frataxin (FXN) necessary to convert the heart of a homozygote to that of a heterozygote. In noncardiac cells, FA heterozygotes have 30-80% of normal FXN levels (17.7-47.2 ng/mg, average 32.5 ng/mg) and FA homozygotes 2-30% normal levels (1.2-17.7 ng/mg, average 9.4 ng/mg). Therefore, an AAV vector would need to augment endogenous in an FA homozygote by >8.3 ng/mg. To determine the required dose of AAVrh.10hFXN, we administered 1.8 × 1011, 5.7 × 1011, or 1.8 × 1012 gc/kg of AAVrh.10hFXN intravenously (IV) to muscle creatine kinase (mck)-Cre conditional knockout Fxn mice, a cardiac and skeletal FXN knockout model. The minimally effective dose was 5.7 × 1011 gc/kg, resulting in cardiac hFXN levels of 6.1 ± 4.2 ng/mg and a mild (p < 0.01 compared with phosphate-buffered saline controls) improvement in mortality. A dose of 1.8 × 1012 gc/kg resulted in cardiac hFXN levels of 33.7 ± 6.4 ng/mg, a significant improvement in ejection fraction and fractional shortening (p < 0.05, both comparisons) and a 21.5% improvement in mortality (p < 0.001). To determine if the significantly effective dose of 1.8 × 1012 gc/kg could achieve human FA heterozygote levels in a large animal, this dose was administered IV to nonhuman primates. After 12 weeks, the vector-expressed FXN in the heart was 17.8 ± 4.9 ng/mg, comparable to the target human levels. These data identify both minimally and significantly effective therapeutic doses that are clinically relevant for the treatment of the cardiac manifestations of FA.

Medical-Legal Partnership Effects on Mental Health, Health Care Use, and Quality of Life in Primary Care: A Randomized Clinical Trial.

PURPOSE: To determine whether an immediate referral to a medical-legal partnership (MLP), compared with a 6-month waitlist control, improved mental health, health care use, and quality of life. METHODS: This trial randomly assigned individuals to an immediate referral or a wait-list control. The MLP involved a collaboration between the primary care clinic and a legal services organization. The primary outcome was stress (6 months) as measured by the Perceived Stress Scale (PSS). Secondary measures included the Center for Epidemiologic Studies Depression Scale; Generalized Anxiety Disorder scale (GAD-7); Patient-Reported Outcomes Measurement Information System (PROMIS); and emergency department (ED), urgent care, and hospital visits. Assessments were at baseline and 3-, 6-, and 9-month follow-ups. Bayesian statistical inference and a 75% posterior probability threshold were used to identify noteworthy differences. RESULTS: Immediate referral was associated with lower PSS scores and higher GAD-7 scores. PROMIS scores were higher for the immediate referral group with respect to several subdomains. At 6 months, the immediate referral group demonstrated 21% fewer ED visits and 75.6% more hospital visits. CONCLUSION: Immediate referral to the MLP was associated with lower stress and a lower rate of ED visits but higher anxiety and a higher rate of hospital visits. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03805126.

Sessile Trichomes Play Major Roles in Prey Digestion and Absorption, While Stalked Trichomes Function in Prey Predation in Byblis guehoi.

Carnivorous plants in the genus Byblis obtain nutrients by secreting viscous glue drops and enzymes that trap and digest small organisms. Here, we used B. guehoi to test the long-held theory that different trichomes play different roles in carnivorous plants. In the leaves of B. guehoi, we observed a 1:2.5:14 ratio of long-stalked, short-stalked, and sessile trichomes. We demonstrated that the stalked trichomes play major roles in the production of glue droplets, while the sessile trichomes secrete digestive enzymes, namely proteases and phosphatases. In addition to absorbing digested small molecules via channels/transporters, several carnivorous plants employ a more efficient system: endocytosis of large protein molecules. By feeding B. guehoi fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA) to monitor protein transport, we found that sessile trichomes exhibited more endocytosis than long- and short-stalked trichomes. The uptaken FITC-BSA was delivered to the neighboring short epidermal cells in the same row as the sessile trichomes, then to the underlying mesophyll cells; however, no signals were detected in the parallel rows of long epidermis cells. The FITC control could be taken up by sessile trichomes but not transported out. Our study shows that B. guehoi has developed a well-organized system to maximize its food supply, consisting of stalked trichomes for prey predation and sessile trichomes for prey digestion. Moreover, the finding that sessile trichomes transfer large, endocytosed protein molecules to the underlying mesophyll, and putatively to the vascular tissues, but not laterally to the terminally differentiated epidermis, indicates that the nutrient transport system has evolved to maximize efficiency.

Comparison of suture-bridge and independent double-row techniques for medium to massive posterosuperior cuff tears: a two-year retrospective study.

BACKGROUND: Transosseous-equivalent suture-bridge (TOE-SB) and independent double-row (IDR) repair techniques were developed to treat rotator cuff tears. The study was designed to prove that both TOE-SB and IDR techniques provided comparable clinical results and retear rate for medium to massive posterosuperior rotator cuff tears, while the surgical time and number of suture anchor used were less in the IDR group. STUDY DESIGN: Level of evidence: level III, Retrospective comparative study. METHODS: Patients with medium to massive posterosuperior rotator cuff tears receiving arthroscopic TOE-SB and IDR between November 2016 to October 2019 were retrospectively enrolled. All patients were confirmed to have grade ≤ 2 fatty infiltration in the muscles of the torn tendons. Revision, concomitant subscapularis tear, acromiohumeral distance < 7 mm, glenohumeral osteoarthritis, partial repair, incomplete repair, partial thickness, or irreparable posterosuperior cuff tear were excluded. Surgical time, number of suture anchor used for the surgery, pre-operative, and post-operative clinical scores such as Constant-Murley score, subjective shoulder value (SSV), and visual analog scale (VAS) were compared. The retear rates between groups were evaluated by ultrasound. RESULTS: Thirty-five IDR and thirty-five TOE-SB repairs were enrolled. The IDR technique required much fewer anchors than TOE-SB did to complete the cuff repair. The mean operation time in IDR and TOE-SB group were 86(18.23), and 114(18.7) (min), respectively (P <  0.01). The mean number of anchors used to complete the cuff repair was 2(0.17) in IDR and 3(0.61) in TOE-SB (P <  0.01). The Constant-Murley score improved from 34.9 ± 6.6 to 80.6 ± 9.4 in the IDR group, and 37.4 ± 6 to 81.9 ± 4.6 in the TOE-SB group (both P <  0.001). SSV improved from 24.6 ± 9.6 to 79.3 ± 10.6 in the IDR, and 27.9 ± 9 to 82.9 ± 6.9 in the TOE-SB group (both P <  0.001). VAS improved from 7.9 ± 0.6 to 1.5 ± 0.7 in the IDR, and 8 ± 0.5 to 1.3 ± 0.6 in the TOE-SB group (both P <  0.001) at final follow-up. No significant difference was found between the retear rates (14.3% in the IDR vs. 17.1% in the TOE-SB, respectively) in the 2-year follow-up. CONCLUSIONS: Both IDR and TOE-SB group provided comparable clinical results and retear rates for medium to massive posterosuperior rotator cuff tears. The surgical time and number of anchors used were less in the IDR group than in the TOE-SB group.

Outcomes of Combined Anterior Cruciate Ligament and Anterolateral Ligament Reconstruction According to GNRB Arthrometer Measurement.

Background and Objectives: To investigate the prognosis of combined anterior cruciate ligament (ACL) and anterolateral ligament (ALL) reconstruction, we used a GNRB (Genourob, Laval, France) arthrometer to measure surgical outcomes. Materials and Methods: This retrospective study reviewed patients who underwent combined ACL and ALL reconstruction and had a minimum follow-up of 2 years. Subjective outcomes, namely the International Knee Documentation Committee (IKDC) evaluation form scale scores and Lysholm scores, were evaluated preoperatively and postoperatively. We used a GNRB arthrometer to test the side-to-side laxity under pressures of 134 and 200 N, and we calculated the differential of the slope of the curves. We also recorded complications. Results: Our study examined 18 patients (mean age: 30.56 ± 8.9 years, range: 19-53) with a mean follow-up of 27.37 ± 3.4 months (range: 24-36). Both Lysholm and IKDC scores were significantly improved following the operation. The GNRB arthrometer measured mean anteroposterior laxity side-to-side as 0.76 ± 0.78 mm and 0.82 ± 0.8 mm under pressures of 134 and 200 N, respectively. The mean side-to-side differential slope under 200 N was 3.52 ± 2.17 µm/N. These values indicated that patients displayed no graft tear or low functional knee instability. All patients had a grade 3 pivot shift preoperatively; only two patients had a grade 1 pivot shift postoperatively, with the rest having a negative pivot shift. Conclusions: Our study revealed that combined ACL and ALL reconstruction has an excellent prognosis. GNRB measurement demonstrated excellent stability, and most patients had no residual pivot shift.

Safety of Intravenous Administration of an AAV8 Vector Coding for an Oxidation-Resistant Human α1-Antitrypsin for the Treatment of α1-Antitrypsin Deficiency.

α1-antitrypsin (AAT) deficiency is a common autosomal recessive hereditary disorder, with a high risk for the development of early-onset panacinar emphysema. AAT, produced primarily in the liver, functions to protect the lung from neutrophil protease; with AAT deficiency, unimpeded neutrophil proteases destroy the lung parenchyma. AAT is susceptible to oxidative damage resulting in an inability to inhibit its target proteases, neutrophil elastase, and cathepsin G. The major sites of oxidative modification on the AAT molecule are methionine residues 351 and 358. We have previously demonstrated that an engineered variant of AAT that resists oxidation by modifying both protein surface methionines (M351V and M358L) provides antiprotease protection, despite oxidative stress. In mice, intravenous delivery of the modified AAT(AVL) variant by AAV serotype 8, AAV8hAAT(AVL), primarily to the liver resulted in long-term expression of an AAT that resists oxidative inactivation. In this study, we evaluated the safety of intravenous administration of AAV8hAAT(AVL) in a dose-escalating, blinded, placebo-controlled toxicology study in wild-type mice. The study assessed organ histology and clinical pathology findings of mice, intravenously administered AAV8hAAT(AVL) at three doses (5.0 × 1011, 5.0 × 1012, and 5.0 × 1013 genome copies [gc]/kg), compared to control mice injected intravenously with phosphate-buffered saline. As previously demonstrated, administration of AAV8hAAT(AVL) resulted in dose-dependent expression of high, potentially therapeutic, levels of serum human AAT protein that persist for at least 6 months. Antibodies against the AAV8 capsid were elicited as expected, but there was no antibody detected against the AAT(AVL) protein generated by the AAV8hAAT(AVL) vector. There was no morbidity or mortality observed in the study. The data demonstrate that intravenous administration of AAV8hAAT(AVL) is safe with no significant adverse effect attributed to AAV8hAAT(AVL) vector at any dose. This study demonstrates that AAV8hAAT(AVL) has a safety profile consistent with the requirements for proceeding to a clinical study.

Arthroscopic diagnosis of long head of biceps tendon instability in refractory anterior shoulder pain: A comparison study between pulley tear and non-tear lesions.

BACKGROUND: Long head of the biceps tendon (LHBT) instability and biceps reflection pulley (BRP) lesions are common cause of refractory anterior shoulder pain. We described a technique using dynamic arthroscopy to determine associated intraarticular pathologies. METHODS: Patients with refractory anterior shoulder pain and arthroscopically-diagnosed LHBT instability were enrolled. LHBT instability and the integrity of BRP and concomitant intra-articular lesions were investigated by ramp test. Demographics and arthroscopic findings were compared between patients with and without BRP tear. RESULTS: Forty patients were enrolled. BRP tear was noted in 25 patients (group A) and superior glenohumeral ligament (SGHL) insufficiency through ramp test in 15 patients (group B). Concomitant intraarticular pathologies were noted in 27 patients, including 19 in group A (76%) and eight in group B (53%), without significant group-wise difference (p = 0.138). The incidence of articular-side subscapularis tear was significantly higher in group A (p = 0.021), and those of the other intraarticular pathologies were similar between groups A and B. Fraying at the articular side of the subscapularis and supraspinatus tendons was frequent in group B, without difference of incidence as compared to group A (p = 0.5 and p = 0.084, respectively). CONCLUSIONS: LHBT instability was a common disorder in patients with refractory shoulder pain. In those patients, dynamic assessment of BRP lesions and SGHL insufficiency and meticulous survey of associated intra-articular pathologies, including subscapularis tear are necessary for making accurate diagnosis and treatment decision.

Comparison of hook plate alone, hook plate augmented with suture anchor, and arthroscopically-assisted tightrope fixation in the treatment of patients with acute type v acromioclavicular joint dislocations.

INTRODUCTION: The best treatment for Rockwood type V acromioclavicular (AC) joint dislocation is unknown. HYPOTHESIS: Hook plate augmented with suture anchor (HA) may have different clinical and radiological results than hook plate alone (H), and arthroscopically assisted TightRope (TR) techniques in treating acute type V AC joint dislocations. MATERIAL AND METHODS: This retrospective study included 71 patients with acute type V AC joint dislocations between December 2010 and August 2018. Patients were categorized into three groups: H group (n=22), HA group (n=23) and TR group (n=26). We measured the coracoclavicular distance (CCD) differences and CCD ratio compared to uninjured side pre-operatively, immediately post-operatively, at 3-month and 2-year after operation. Clinical outcomes were assessed as well at the same time points. Loss of correction was determined by the CCD difference and ratio between surgical and uninjured sides. RESULTS: The mean age and follow-up period were 41.8±24.7 years and 30.2±4.3 months, respectively. No significant differences were found in the demographic data between the three groups. The HA group presented a trend of less overcorrection but without significance compared with the H group at immediately post-operation, 3-month, and 2-year follow-up. (CCD difference: -2.4mm vs. -3.7mm, -1.6mm vs. -1.8, and 0.2mm vs -1.9mm, CCD ratio: 67.7% vs. 40.9%, 79.3% vs. 70.1%, and 100.6% vs. 86.5%, respectively). The HA group also had significantly less loss of correction compared with the TR group at 3-month and 2-year after the operation (CCD difference: -1.6mm vs. 1.6mm, 0.2mm vs. 2.4mm; CCD ratio: 79.3% vs. 122.2%, 100.6% vs. 136.1%, all p<0.05). All three methods achieved significant improvement in function and pain without inter-group differences. No coracoid-related or tunnel complications occurred. DISCUSSION: The hook plate alone, and hook plate with suture anchor augmentation techniques provided less residual vertical instability compared to TightRope fixation at 2-year follow-up. The patient-reported functional outcomes were promising and comparable among the three groups. LEVEL OF EVIDENCE: III, Retrospective comparative therapeutic trial.

Arthroscopic Pan-Capsular and Transverse Humeral Ligament Release with Biceps Tenodesis for Patients with Refractory Frozen Shoulder.

Arthroscopic capsular release allows direct visualization and release of inflamed tissues in refractory frozen shoulder. The reticular neural network in the long head of the biceps tendon (LHBT) and nerve endings of the transverse humeral ligament (THL) might be responsible for shoulder pain. We hypothesized that patients with painful refractory frozen shoulder benefited from pan-capsular release, THL release, and LHBT tenodesis. The LHBT tenodesis decreased the possibility of LHBT instability. The balance of the shoulder joint was maintained after such extensive release. From October 2013 to June 2019, patients with painful refractory frozen shoulder were enrolled consecutively at the same institute. All patients received arthroscopic pan-capsular, THL release, and suprapectoral LHBT tenodesis with a minimum of 2-year follow-up. Preoperative and postoperative shoulder range of motion (ROM), pain visual analog scale (PVAS), subjective shoulder value (SSV), constant score, LHBT score, acromio-humeral distance (AHD), and critical shoulder angle (CSA) were recorded. In total, 35 patients with an average age of 53.1 ± 9 years were enrolled. The average follow-up period was 24 ± 1.5 months. Forward elevation improved from 105.1° ± 17° to 147° ± 12° (p < 0.001), external rotation improved from 24.1° ± 13.3° to 50.9° ± 9.7° (p < 0.001), and internal rotation improved from L3 to T9 (p < 0.001), respectively, at final follow-up. PVAS improved from 7.3 ± 1.1 to 1.8 ± 0.6 (p < 0.001), constant score from 23.4 ± 11 to 80.7 ± 5.2 (p < 0.001), and SSV from 27.7 ± 10.5 to 77.4 ± 3.8, respectively, at follow-up. No differences were found in AHD and CSA after surgery (p = 0.316, and p = 0.895, respectively). Patients with painful refractory frozen shoulder benefited from pan-capsular and THL release. A radiographically balanced shoulder joint was maintained even after such extensive release.

Recurrent Shoulder Instability after Arthroscopic Bankart Repair in an Elite Baseball Pitcher-A Case Report.

A 16-year-old right-handed male pitcher had a first-time right anterior shoulder dislocation during a baseball game. X-ray and MRI revealed no apparent glenoid bone loss or Hill-Sachs lesion, but an anterior labroligamentous periosteal sleeve avulsion (ALPSA) lesion with mild posterolateral decompression of the humerus head. His instability severity index score (ISIS score) was 5 with an on-track lesion. He had an arthroscopic Bankart repair using two all-suture anchors and returned to pitching 6 months after the index surgery. However, he had an unstable sensation after 50 pitches during a game one year postoperatively. This time, he presented with a significant Hill-Sachs lesion and a recurrent APLSA lesion. His ISIS score was 6 with an on-tract lesion. During the arthroscopic examination, the previous suture was stable, while anterior capsuloligament tissues were dislodged from sutures, and a Hill-Sachs lesion was observed. This time, a revision arthroscopic Bankart repair and Remplissage procedure were done on him with four double-loaded soft tissue anchors. Pitchers often develop more external rotation in their throwing arm because of a repetitive stretch of the anterior shoulder capsule and ligaments during pitching. The decrease in external rotation after surgery may limit the pitching speed of the pitcher, making a return to play (RTP) more difficult. There is still a paucity of best evidence to revise a failed arthroscopic Bankart repair in the dominant arm of a pitcher. Arthroscopic Bankart repair and Remplissage procedure have gained increasing popularity because they can provide a stable shoulder without harvesting the coracoid. The Latarjet procedure provides a high RTP rate; however, we did not perform it in the revision surgery and decided to revise the Bankart lesion again on its own with a Remplissage procedure, even with his ISIS score being 6 before the revision surgery. A salvage Latarjet procedure is left as a bailout procedure.