Failure and complication rates following meniscal all-inside and inside-out repairs: A systematic review and meta-analysis.

PURPOSE: This study examines failure rates, complication rates and patient-reported outcome measures (PROMs) for meniscal all-inside (AI) and inside-out (IO) repair techniques. METHODS: A systematic search was conducted on PubMed, Embase and Cochrane (inception to January 2024) assessing for Level I-III studies evaluating outcomes after meniscal repair. The primary outcome regarded differences in failure rates between AI and IO repair techniques. Secondary outcomes included a comparison of complication rates and PROMs. Quality assessment was performed using the Grading of Recommendations Assessment, Development and Evaluation and Methodological Index for Non-Randomized Studies criteria. A meta-analysis was conducted for outcomes reported by more than three comparative studies. RESULTS: A total of 24 studies (13 studies and 912 menisci for AI vs. 17 studies and 1,117 menisci for IO) were included. The mean follow-up ranges were 22-192 months (AI) and 18.5-155 months (IO). The overall reported AI failure rate ranged from 5% to 35% compared to 0% to 25% within the IO group. When comparing meniscal repair failure rates in the setting of concomitant anterior cruciate ligament reconstruction, the AI group had a failure rate (AI: 5%-34%; IO: 0%-12.9%). The complication rate ranged from 0% to 40% for AI and 0% to 20.5% for IO. Post-operative PROM scores ranged from 81.2 to 93.8 (AI) versus 89.6 to 94 (IO) for IKDC and 4.0-7.02 (AI) versus 4.0-8.0 (IO) for Tegner. Upon pooling of six comparative studies, a significantly lower failure rate favouring the IO technique was observed (15.9% AI vs. 11.1% IO; p = 0.02), although this result was influenced by a study with a predominantly elite athlete population. Moreover, no significant differences were found regarding complication rates between cohorts (7.3% AI vs. 4.8% IO; p = 0.86). CONCLUSION: The present study underscores comparable clinical success between AI and IO meniscal repair techniques, with both techniques demonstrating similar complication rates. However, the AI repair technique was associated with 1.77 times higher odds of failure compared to the IO cohort. LEVEL OF EVIDENCE: Level III.

The Role of SIRT1 in Leukemia.

OPINION STATEMENT: Leukemia is a type of hematological malignancy (HM) caused by uncontrolled proliferation, apoptosis, and differentiation of hematopoietic stem cells (HSCs). Leukemia cells proliferate greatly in the bone marrow (BM), infiltrate other tissues and organs, and affect the normal hematopoietic function. Although the emergence of new targeted agents and immune agents has improved the prognosis of patients, due to the complex pathogenic factors and heterogeneity of leukemia, there are still some patients with poor prognosis. Recent studies have shown that silent information regulator 1 (SIRT1) is involved in the proliferation, apoptosis, metabolism, and senescence of leukemia cells. As a double-edged sword in leukemia cells, SIRT1 can both promote and inhibit the growth of leukemia cells. Since its mechanism of action has not been elucidated, it is urgent to explore the regulatory mechanism of SIRT1 in leukemia. In this review, we discussed the mechanisms of SIRT1 in different aspects of leukemia, providing a theoretical basis for the treatment of patients with leukemia.

TAPP versus lichtenstein techniques for bilateral inguinal hernia repair: A systematic review and meta-analysis.

Inguinal hernia repair is one of the most common surgical procedures performed worldwide. However, very few studies report data on the laparoscopic advantages of bilateral inguinal hernia (BIH) repair over the open approach. Therefore, this meta-analysis was conducted to compare the effectiveness of the laparoscopic trans-abdominal pre-peritoneal (TAPP) technique with the open Lichtenstein repair technique (OLR) for the repair of BIH. A detailed literature search was conducted on PubMed, Google Scholar, and Cochrane Library for comparative studies between TAPP and OLR techniques for repair of BIH. RevMan Version 5.4 was used for data analysis. The Inverse Variance statistical method was used to analyze the primary outcomes and the Mantel-Haenszel statistical method was used to analyze the secondary outcomes. The effect measure was reported as a Risk Ratio. There was no significant difference in recurrence between the two groups. A significant difference was seen in duration of post-operative hospital stay, operative time, pain score on VAS criteria on post-operative Day 1, pain score on VAS criteria on post-operative Day 7, and complications, all in the favor of TAPP except for operative time which was in the favor of OLR. TAPP was found to be superior to OLR in terms of duration of post-operative hospital stay, pain scores on VAS criteria on post-operative days 1 and 7, and complications, whereas OLR was found superior only in terms of operative time. For recurrence, there was no significant difference between the two groups.

Biomechanical comparison of the tensile strength of fixation implants used for pull-out repair of medial meniscus posterior root tear.

PURPOSE: Medial meniscus posterior root tears (MMPRT) pull-out repair aims to restore the meniscus' anatomical structure. Different implants are utilized for thread fixation in the pull-out repair technique for MMPRT. However, biomechanical evidence comparing the fixation strengths of these implants remains unavailable. This study investigated the tensile strength of three fixation implants in porcine knee models of MMPRT pull-out repair. METHODS: This study categorized 30 porcine MMPRT models undergoing pull-out repair into three groups (10 specimens each) based on the implant utilized for fixation, including double spike plate, metallic interference screw (IFS), and resorbable IFS fixed group. A tensile tester was used to track the suture wire threaded to the medial meniscus anterior root. The displacement length was recorded after 10 and 20 loading cycles (10-30 N, 100 mm/min cross-head speed). Each specimen was then stretched to failure (50 mm/min cross-head speed), failure modes were recorded, and structural properties (maximum load, linear stiffness, elongation at failure, and elongation at yield) were compared. Fisher's exact test and one-way analysis of variance were utilized to assess the differences. RESULTS: No significant differences in displacement length, upper yield load, maximum load, linear stiffness, elongation at yield, elongation at failure, and frequency of failure mode were observed between the three groups. CONCLUSION: All implants were comparable in terms of fixation strength. Thus, resorbable interference screws may be particularly useful in this technique and does not require implant removal surgery. LEVEL OF EVIDENCE: IV.

Comparative analysis of functional outcomes in arthroscopic repair for traumatic and non-traumatic rotator cuff injuries.

BACKGROUND: The impact of the etiology of rotator cuff injury (RCI) on outcomes after rotator cuff repair remains unclear. This study aimed to evaluate the postoperative outcomes of patients with RCIs of different etiologies and identify the risk factors affecting prognosis. METHODS: This study included 73 patients with RCI who underwent arthroscopic rotator cuff repair. The patients were categorized into either a traumatic group or a non-traumatic group based on their history of trauma. Preoperative and postoperative assessments included shoulder range of motion, muscle strength, and physical examination findings specific to the shoulder for both groups. Clinical differences between arthroscopic repair of traumatic and non-traumatic RCIs were evaluated using univariate analysis. Logistic regression analysis determined independent risk factors for rotator cuff repair prognosis. RESULTS: Among the 73 patients, 31 were in the traumatic group and 42 in the non-traumatic group, with a minimum postoperative follow-up of 12 months and a mean follow-up of 13.8 months. The duration of the disease was significantly longer in the non-traumatic group compared with the traumatic group (P < 0.001). The mean tear area was more significant in the traumatic group than in the non-traumatic group (P = 0.003), and the preoperative pain level and functional scores were better in the non-traumatic group compared with the traumatic group. Postoperatively, there were no differences between the two groups regarding scores, joint mobility, strength, and complications. At 12 months postoperatively, multivariate regression analysis indicated that full-layer tear (OR = 5.106, 95% CI: 1.137-22.927, P = 0.033), fat infiltration (OR = 6.020, 95% CI: 1.113-32.554, P = 0.037), and tear area (OR = 6.038, 95% CI: 2.122-17.177, P < 0.001) significantly affected the University of California at Los Angeles (UCLA) score. CONCLUSION: Compared with non-traumatic RCI, traumatic RCI presents with more pronounced pain and impaired joint function preoperatively yet demonstrates comparable postoperative clinical outcomes. Full-layer tears, fat infiltration, and large tear areas are unfavorable factors affecting rotator cuff repair, and postoperative rehabilitation management of these patients should be emphasized.

Prediction of homologous recombination deficiency from routine histology with attention-based multiple instance learning in nine different tumor types.

BACKGROUND: Homologous recombination deficiency (HRD) is recognized as a pan-cancer predictive biomarker that potentially indicates who could benefit from treatment with PARP inhibitors (PARPi). Despite its clinical significance, HRD testing is highly complex. Here, we investigated in a proof-of-concept study whether Deep Learning (DL) can predict HRD status solely based on routine hematoxylin & eosin (H&E) histology images across nine different cancer types. METHODS: We developed a deep learning pipeline with attention-weighted multiple instance learning (attMIL) to predict HRD status from histology images. As part of our approach, we calculated a genomic scar HRD score by combining loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST) from whole genome sequencing (WGS) data of n = 5209 patients across two independent cohorts. The model's effectiveness was evaluated using the area under the receiver operating characteristic curve (AUROC), focusing on its accuracy in predicting genomic HRD against a clinically recognized cutoff value. RESULTS: Our study demonstrated the predictability of genomic HRD status in endometrial, pancreatic, and lung cancers reaching cross-validated AUROCs of 0.79, 0.58, and 0.66, respectively. These predictions generalized well to an external cohort, with AUROCs of 0.93, 0.81, and 0.73. Moreover, a breast cancer-trained image-based HRD classifier yielded an AUROC of 0.78 in the internal validation cohort and was able to predict HRD in endometrial, prostate, and pancreatic cancer with AUROCs of 0.87, 0.84, and 0.67, indicating that a shared HRD-like phenotype occurs across these tumor entities. CONCLUSIONS: This study establishes that HRD can be directly predicted from H&E slides using attMIL, demonstrating its applicability across nine different tumor types.

Agonist-antagonist myoneural interface surgery on the proprioceptive reconstruction of rat hind limb.

Currently, prosthesis users rely on visual cues to control their prosthesis. One reason for this is that prostheses cannot provide users with proprioceptive functional signals. For this reason, we propose an agonist-antagonist myoneural interface (AMI) surgery. We examined how this surgery affects the restoration of motor function and proprioceptive reconstruction in the hind limb of Sprague-Dawley rats. The procedure entails grafting the soleus muscle, suturing the two tendon ends of the soleus muscle, and anastomosing the tibial and common peroneal nerves to the soleus muscle. We found that, following surgery, AMI rats exhibited improved neurological repair, shorter walking swings, braking, propulsion, and stance times, and greater compound action potentials than control rats. This means that in rats with neurological impairment of the hind limb, the proposed AMI surgical method significantly improves postoperative walking stability and muscle synergy. AMI surgery may become an option for regaining proprioception in the lost limb.

Nerve Coaptation in 2023: Adjuncts to Nerve Repair Beyond Suture.

Effective nerve coaptation entails tensionless repair of healthy fascicles with intact fascicular architecture and a well-vascularized environment, supportive of the regenerative cellular behaviors of neurons, immune cells, and Schwann cells. Suture coaptations have historically been used to ensure that these criteria are met for end-to-end repair, nerve transfers, and allograft or autograft reconstructions; however, unfortunately, overall restoration of function remains poor. As optimal coaptation is required for return of sensorimotor function, adjunct biomaterials are increasingly being enlisted attempting to optimize these suture-based coaptations. The purpose of this review was to discuss the biological, preclinical, and clinical data for the use of fibrin glue and nerve wraps made of type 1 collagen, porcine small intestine submucosa, chitosan, and human amniotic membrane. This study provides available data on each material's ability to optimize the regenerative potential of nerve repair as well as available outcomes data. Although each biomaterial discussed has benefits to nerve regeneration, at large, data remain heterogeneous, and continued investigation is required to fully understand the specific mechanisms involved and the long-term potential clinical impacts each can provide for improvement of sensorimotor outcomes.

Management of "Long" Nerve Gaps.

Long-gap nerve injuries offer unique physiological and logistical treatment challenges to the reconstructive surgeon. Options include nerve autograft, processed nerve allograft, nerve transfers, and tendon transfers. This review provides an evidence-framed discussion regarding the pros and cons of these diverse approaches.

Treatment of Anterior Shoulder Instability: A Comprehensive Review.

Anterior shoulder instability is a complex spectrum of pathology characterized by excessive translation of the humeral head across the glenoid, leading to apprehension, subluxation, and dislocation. Diagnosis and classification require a thorough clinical history, physical examination, and imaging to appropriately determine the severity of instability. Depending on the individual patient anatomy and severity of instability, there exist many management options that are well-positioned to successfully treat this pathology and allow patients to return to prior functional levels. Treatment options available are conservative management, arthroscopic or open Bankart repair, remplissage, open or arthroscopic Latarjet, and glenoid bone grafting. Each of these options provides unique advantages for the surgeon in treating a subset of patients along the spectrum of disease. Selection of treatment modality depends upon the number of instability events, appropriate quantification, classification bone loss, presence of associated soft tissue injuries, and patient-specific goals regarding return of function. The purpose of this review was to present an evidence-based approach to the investigation, treatment selection, and follow-up of anterior shoulder instability. Individualized patient care is required to optimally address intra-articular pathology, restore stability and function, and preserve joint health for all.

Optimizing Rehabilitation for Nerve Gap Repair: Evidence-Based Recommendations.

Peripheral nerve surgeries are a complex undertaking that require a multifaceted team approach. For optimal outcomes, early involvement of therapy, planning with the surgical team, and communication with the patient are crucial. This facilitates compliance and is an integral component of the recovery process after these large procedures.

Cutting-Edge Approaches for Nerve Debridement Prior to Repair.

Peripheral nerve injuries can be devastating. Although neuropraxic and some axonotmesis injuries will recover spontaneously, nerve repair or reconstruction is required to restore function in high-grade axonotmesis or neurotmesis injuries. The first step of nerve repair or reconstruction is adequate nerve debridement with removal of necrotic and fibrous tissues. Debridement decreases neuroma formation at the repair site and produces an optimal surface for axonal regeneration. This article discusses nerve debridement, including the goals of debridement, debridement techniques, and signs of adequate nerve debridement before repair.

The Role of Nerve Tension on Nerve Repair Success.

Peripheral nerve injuries that are not acutely repaired may lead to a nerve gap because of the surrounding zone of injury and elastic recoil of nerve tissue after laceration. This can result in tension across the repair site during primary neurorrhaphy. Decades of basic science literature using in vivo models consistently demonstrate a relationship between increasing strain at a neurorrhaphy site and compromised microvascular blood flow. Clinical and laboratory data suggest tension-free repairs are associated with optimal outcomes; in the setting of a short segmental nerve gap, data suggest primary repair may continue to yield good functional results. In the case of high strain, nerve grafting or other methods should be considered given poor results of primary repairs performed under high tension because of local ischemia and fibrosis on a cellular level.

Concepts of Pain Management Following Nerve Injuries: Multidisciplinary Approach.

Purpose: A systematic review to identify treatment approaches for the management of pain following peripheral nerve injury. Methods: A published literature search was performed for the concepts of peripheral nerve injury and pain management with related synonyms. The strategies were created using a combination of controlled vocabulary terms and keywords and were executed in Embase.com, Ovid-Medline All, and Scopus from database inception. Database searches were completed on August 22, 2023. Results: The initial search resulted in a total of 1,793 citations. In total, 724 duplicates were removed, leaving 1,069 unique citations remaining for analysis. This review excluded all papers that were not specific to pain following peripheral nerve injury. Case and cohort studies (n < 5) were also excluded. Thirty-two articles on pain management strategies after peripheral nerve injury remained, with years of publication ranging from 1981 to 2023. An additional four articles were identified by manual search. Of the 36 articles reviewed, 15 articles reported on the approach to the treatment of pain after a peripheral nerve injury, and the other 22 articles consisted of cohort and case series studies. Conclusions: There is a lack of literature describing efficacy of various treatment strategies for pain following peripheral nerve injuries. Few studies provide clear, stepwise clinical guidance for practicing physicians and other health care providers on the treatment of these complicated patients.

The Role of Vascularized Nerve Grafting in Upper Extremity Reconstruction: A Systematic Review.

Purpose: Vascularized nerve grafts (VNGs) have been proposed as encouraging alternatives to conventional nerve grafting; however, there is ongoing debate regarding the clinical advantages of the approach compared with standard grafting. This review aims to gather and analyze reported cases of upper extremity nerve repair using VNGs documented in the published literature. Methods: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed/MEDLINE, Embase, and Cochrane were searched. Inclusion criteria for this review included the following: (1) human subjects or cadaveric studies, (2) describing a vascularized nerve grafting procedure or suggesting a nerve and vascular supply for a potential vascularized nerve graft, and (3) upper extremity nerve repair in clinical studies. Results: Data were extracted from 45 clinical studies. Of 535 patients, the most common injury pattern was root avulsion and rupture (88.7%). The most utilized VNG was the ulnar nerve (72.8%), followed by nerve to long head of triceps (8.8%) and sural nerve (8.2%); most common recipients were median (57.6%), axillary (12.5%), and musculocutaneous nerves (11.9%). Between patients who had medical research council scale scores, 69% had functional (M3 and above) motor and 72.7% sensory (S3<) recovery. Conclusions: Vascularized nerve grafts can increase the odds of functional gain in challenging conditions such as large nerve gaps, nerve avulsions, ruptures, and scarred and irradiated beds. With the exception of well-known VNG options, literature on alternative VNGs is largely confined to case reports and series, with additional published cases, outcomes, and basic science research needed to establish the role of VNGs in nerve repair. Clinical relevance: Our findings support the promise of VNGs for complex cases of nerve reconstruction. Evidence from published cases also indicates that VNGs enhance motor and sensory function recovery compared with traditional nerve grafting.

A Systematic Review to Compare Electrical, Magnetic, and Optogenetic Stimulation for Peripheral Nerve Repair.

The purpose of this systematic review was to assess the currently available evidence for the use of external stimulation to modulate neural activity and promote peripheral nerve regeneration. The most common external stimulations are electrical stimulation (ES), optogenetic stimulation (OS), and magnetic stimulation (MS). Understanding the comparative effectiveness of these stimulation methods is pivotal in advancing therapeutic interventions for peripheral nerve injuries. This systematic review focused on these three external stimulation modalities as potential strategies to enhance peripheral nerve repair (PNR). We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework to systematically evaluate and compare the efficiency of ES, OS, and MS in PNR. The review included studies published between 2018 and 2023 using ES, OS, or MS for PNR focused on enhancing recovery of peripheral nerve injuries in rodent models identified through PubMed and Google Scholar. The search strategies and inclusion criteria identified 19 studies (13 ES, 4 OS, and 2 MS) for detailed analysis, focusing on critical parameters such as functional recovery, histological outcomes, and electrophysiological data. Although ES demonstrated a consistent improvement in all the analyses, high-frequency repetitive MS (HFr-MS) emerged as a promising modality. HFr-MS demonstrated accelerated PNR, as histological and electrophysiological evidence indicated. In contrast, OS exhibited superior functional recovery outcomes. Notable limitations include constrained MS and OS data sets and the challenge of comparing relative improvements because of methodological diversity in evaluation techniques. Our findings underscore the potential of HFr-MS and OS in PNR while emphasizing the critical need for standardized testing protocols to facilitate meaningful cross-study comparisons. External stimulations have the potential to improve functional recovery in patients with nerve injury.

Exercise testing in patients with tricuspid regurgitation undergoing transcatheter tricuspid valve intervention.

BACKGROUND: Transcatheter tricuspid valve intervention (TTVI) has shown promising results with persistent reduction of tricuspid regurgitation (TR) and improvements in functional class and quality of life (QOL). OBJECTIVES: To analyze the impact of TTVI on maximal and submaximal exercise capacity (SEC). METHODS: Constant work-rate exercise-time (CWRET) testing reflects SEC, which is more likely to be relevant for daily life activities and provides more differentiated physiological insight into the nature of exercise intolerance. Thus, 30 patients undergoing TTVI (21 direct annuloplasty and 9 edge-to-edge repair) received cardiopulmonary exercise testing (CPET) and CWRET (at 75% of maximum work rate in the initial CPET) before and 3 months after TTVI. RESULTS: Patients' age was 80.5 [74.8-82.3] years and 53.3% were female. TR reduction ≥ 2 grades was achieved in 93.3% (TR grade ≤ moderate in 83.3%). Echocardiography revealed improved right ventricular (RV) characteristics with decreased RV basal diameter (47.0 mm [43.0-54.3] vs. 41.5 mm [36.8-48.0]; p < 0.001) and decreased inferior caval vein diameter. CWRET testing showed a significantly improved SEC (246.5 s [153.8-416.8] vs. 338.5 s [238.8-611.8] p = 0.001). Maximum oxygen uptake showed a positive trend without statistically significant differences (9.9 ml/min/kg [8.6-12.4] vs. 11.7 ml/min/kg [9.7-13.3]; p = 0.31). In contrast to the six-minute-walking distance (6MWD), SEC correlated moderately with effective regurgitation orifice area reduction (r = 0.385; p = 0.036), increased cardiac output (r = 0.378; p = 0.039), and improved QOL (r = 387; p = 0.035). CONCLUSION: Improvements in exercise capacity after TTVI mainly occur in the submaximal rather than in the maximal exercise range and correlate with hemodynamic effects and QOL. This may have a methodological impact on assessment of exercise capacity in these patients.

Impact of DNA Repair Deficiency in the Evolving Treatment Landscape of Bladder Cancer.

PURPOSE OF REVIEW: This review explores the current landscape of treatments which target the DNA damage response (DDR) in metastatic and muscle-invasive bladder cancer. It emphasizes recent clinical trials which integrate DDR inhibitors with standard chemotherapy and immunotherapy. RECENT FINDINGS: Noteworthy findings include the ATLANTIS trial, which demonstrated prolonged progression-free survival (PFS) in DDR biomarker-selected patients using PARP inhibitors as maintenance after standard chemotherapy. Trials such as BAYOU, which combined immunotherapy with PARP inhibition, similarly suggested a potential therapeutic benefit in DDR biomarker-selected patients with bladder cancer. Efforts to develop bladder-sparing treatment regimens based on DDR-associated mutational profiles, such as the RETAIN and HCRN 16-257 trials, have had mixed outcomes to date. There are now ongoing efforts to combine DDR inhibitors with the newest bladder cancer therapies, such as antibody-drug conjugates. This review highlights the most recent advances in targeting DNA repair deficiency in the evolving treatment landscape of bladder cancer.

Therapeutic effects of paeonol on non­small cell lung cancer cells via regulation of the MAPK pathway.

The present study aimed to investigate the molecular mechanisms by which paeonol impedes DNA damage repair, induces apoptosis and inhibits cell viability via the mitogen-activated protein kinase (MAPK) pathway. Firstly, normal human bronchial epithelial cells (BEAS-2B) and non-small cell lung cancer cells (H1299) were employed in the study as cellular models. Following cultivation, the cells were divided into experimental and control groups, and were treated with different concentrations of paeonol. Subsequently, various techniques, including western blotting, Cell Counting Kit-8, colony formation, TUNEL and comet assays were conducted to evaluate the effects of paeonol on cell viability, colony-forming ability, apoptosis levels and DNA damage in H1299 cells. According to the experimental results, paeonol significantly reduced the viability and colony formation ability of H1299 cells, but substantially increased apoptosis and DNA damage. These effects were enhanced in response to higher concentrations of paeonol. Furthermore, western blot analysis revealed that paeonol treatment decreased the protein levels of B-cell lymphoma 2 and breast cancer susceptibility gene 1, while it increased the expression levels of cleaved-PARP, cleaved-caspase 3, γH2AX and P21. Additionally, the phosphorylated levels of extracellular signal-regulated kinase 1, c-Jun N-terminal kinase and P38 within the MAPK signaling pathway were diminished. Collectively, the present study demonstrated that paeonol may inhibit the metabolic activity and proliferative capability of H1299 cells, and that it could promote apoptosis and obstruct DNA damage repair by modulating the MAPK signaling pathway.