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Background: The medial collateral ligament (MCL) is frequently involved in injuries around the knee but is uncommonly treated surgically. There are various techniques to reconstruct the medial side of the knee, which have varying outcomes. Purpose/hypothesis: The purpose of the present systematic review and meta-analysis is to describe the clinical results of surgical management of acute and chronic isolated grade III MCL injury using various functional scores, such as IKDC, Lysholm, and VAS, and to ascertain complication rates associated with these interventions. Methods: A systematic review was performed according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines, and two independent authors (L.F and A.M) conducted a comprehensive search across multiple databases (PubMed, Web of Science, and Scopus). They reviewed each article's title and abstract for studies available until April 2024. The search terms used were "((MCL) OR (Medial collateral ligament)) AND (injuries) AND (treatment)". The full texts of the studies were evaluated when eligibility could not be assessed from the title and abstract. Results: The pooled proportion (percentage) of complications from the three studies reporting data on surgery for the MCL acute stage was 15.3% with 95% CI [6.1% to 24.6%]. No complications were reported in studies reporting surgery in the chronic stage. Marked resolution of pain was observed with the mean VAS Score for pain at the final follow-up after surgery for MCL injury in the acute stage was 0.4 with 95% CI [-0.04 to 0.84]. The mean IKDC score at the final follow-up in the three studies reporting data on surgery for the MCL in the acute stage was 79.39 with 95% CI [67.96 to 90.82], and in the chronic stage, was 85 with 95% CI [83.02 to 86.98]. The mean Lysholm Score at the final follow-up after surgery for MCL injury in the chronic stage was 83.04 with 95% CI [75.24 to 94.84], and in the acute stage was 95 with 95% CI [91.76 to 98.24]. Conclusion: This systematic review found that functional outcomes regarding IKDC and LYSHOLM scores were comparable for surgeries performed in acute and chronic MCL tears. There was a marginally increased risk of complication in surgeries performed for acute MCL tears. Compared to the acute phase, a marked resolution of pain was observed at the final follow-up after surgery for MCL injury. Study Design: Systematic review; level of evidence, 4.. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to conduct a comprehensive assessment of MLKI outcome studies in order to ascertain the overall rates of return to sport following MLKI. Methods: A systematic review was conducted based on the PRISMA guidelines. Quality assessment of the systematic review was performed using the MINORS Score. The following search terms were browsed in the title, abstract, and keyword fields: "multiligament knee" or "MLKI" AND "return to sport" or "sports activity" or "athletes" or "sports" or "sportsman". The resulting measures extracted from the studies were the rate of RTS, level of RTS, complications, revision surgery, Tegner, International Knee Documentation Committee (IKDC) Lysholm and anterior cruciate ligament-return to sport after injury (ACL-RSI). Results: A total of 439 patients were included in the study, of whom 383 (87.2%) were male and 56 (22.8%) were female. The mean age at surgery was 28.06 ± 8.93 years. The mean time from injury to surgery was 97.68 ± 127.81 weeks, while the mean follow-up was 42.83 ± 39.22 months. Of 312 patients who completed the follow-up and reported to be sportsmen before surgery, 184 (58.97%) returned to the same or higher pre-injury level, 58 (18.58%) returned to a lower level, while 69 (22.11%) did not return to sports activity. The author analysed the Tegner score in three studies and noted a decrease compared to the pre-injury level (from 7.12 ± 0.8 pre-injury to 4.59 ± 0.57 at the final follow-up; p < 0.001). At the final follow-up, 4 studies analysed IKDC with a mean value of 75.14 ± 9.6, 3 reported a mean Lysholm of 51.81 ± 27.6, and two reported a mean ACL-RSI of 64.82 ± 0.149. Among the 439 patients, a total of 90 (20.5%) complications/re-operations were reported, while a total of 29 (6.6%) failures were recorded. Conclusions: Return to sport after MLKI occurs in approximately 75% of surgically treated patients, though return to high-level sport is about 60% of the patients. Furthermore, one in five patients report complications, while the failure rate is relatively low (< 7%). Level of Evidence: Systematic review of level 4. [ABSTRACT FROM AUTHOR]

Anterior cruciate ligament and meniscus tears are common among sports injuries. There are different techniques for addressing anterior cruciate ligament and meniscus tears, with distinct indications, advantages, and disadvantages. We present the case of a 23-year-old male who underwent right anterior cruciate ligament reconstruction and posterior horn medial meniscus repair using an all-inside technique via superficial medial collateral ligament (sMCL) pie-crusting. Clinical examination and radiological investigations a few months later identified calcifications on the medial side of the right knee. We diagnosed the patient with heterotopic ossification post-sMCL pie-crusting; no apparent causal factors were present. To our knowledge, there have been no documented instances of heterotopic ossification following sMCL pie-crusting. In conclusion, heterotopic ossification may occur after sMCL pie-crusting; further studies are needed on this subject. [ABSTRACT FROM AUTHOR]

Introduction and Purpose: This article presents a comprehensive analysis of the risks and benefits associated with downhill skiing. The article elucidates the prevalence and etiology of common injuries, while also delineating the salutary effects of engaging in the sport. Methods: A literature search was conducted using PubMed and Google Scholar, focusing on articles from 2019 to 2024, including observational studies, clinical trials, meta-analyses and systematic reviews. State of Knowledge: Skiing is a globally popular winter sport, attracting millions of enthusiasts each year. The sport's combination of outdoor adventure, social activity, and the allure of winter landscapes contribute to its enduring global popularity. Despite its global popularity, skiing carries a significant risk of injury, with knee injuries, particularly ACL sprains, being the most common, especially among women. Despite these risks, alpine skiing offers significant physical health benefits, including improved cardiorespiratory fitness, muscle strength and mental health, making it a beneficial lifelong sport, particularly for older adults. Conclusion: It is notable that while injuries such as ACL sprains and fractures are prevalent, particularly among beginners and those who engage in risk-taking activities, the sport also offers significant health benefits. Alpine skiing has been demonstrated to enhance cardiorespiratory fitness, muscle strength, and mental well-being, thereby conferring significant benefits that extend throughout the lifespan, despite the potential for injury.

Simple Summary: Bispecific antibodies are a novel type of immune-based therapy used to treat patients with non-Hodgkin's lymphoma. This review article will help define the current treatment landscape of non-Hodgkin's lymphoma and detail ways in which bispecific antibodies fit in the current management paradigm, with special attention paid to diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. B-cell non-Hodgkin's lymphoma (NHL) refers to a heterogenous group of diseases, all of which have a wide range of treatment strategies and patient outcomes. There have been multiple novel, immune-based therapies approved in NHL in the last decade, including bispecific antibodies (BsAbs) and chimeric antigen receptor therapy (CAR-T). With a host of new therapies, an important next step will be determining how these therapies should be sequenced in contemporary management strategies. This review seeks to offer a framework for the ways in which BsABs can be incorporated into the current management paradigm for NHL, with special attention paid to diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). [ABSTRACT FROM AUTHOR]

Semantic information has started to be used in localization methods to introduce a non-geometric distinction in the environment. However, efficient ways to integrate this information remain a question. We propose an approach for fusing data from different object classes by analyzing the posterior for each object class to improve robustness and accuracy for self-localization. Our system uses the bearing angle to the objects' center and objects' class names as sensor model input to localize the user on a 2D annotated map consisting of objects' class names and center coordinates. Sensor model input is obtained by an object detector on equirectangular images of a 360° field of view camera. As object detection performance varies based on location and object class, different object classes generate different likelihoods. We account for this by using appropriate weights generated by a Gaussian process model trained by using our posterior analysis. Our approach follows a systematic way to fuse data from different object classes and use them as a likelihood function of a Monte Carlo localization (MCL) algorithm. [ABSTRACT FROM AUTHOR]

The term "Unhappy Triad", coined by O'Donoghue, reflects a severe knee injury with rupture of the medial collateral ligament, medial meniscus, and anterior cruciate ligament. The triad is primarily a sports injury, and patients' recovery is 6 to 12 months. Material/Methods: 70 patients with "O'Donoghue's triad" were studied. Total anterior cruciate ligament rupture was reconstructed with patellae ligament autograft; medial meniscus tear was treated with partial meniscectomy; and medial collateral ligament injury was treated conservatively at 1 month before surgery. The aim of the study is to establish the epidemiology of the injury: age and gender distribution, distribution by types of sports in patients with "O'Donoghue's Triad" after arthroscopic treatment. 222 persons were examined in two stages – first, 187 with various soft tissue injuries of the knee, after surgical treatment, including persons with the triad, and second, 70 patients with O'Donoghue's triad. Results: The study shows that among 18-19-year-olds, the triad was found in 4 people; from 20 to 29 in 34, from 30 to 39 in 23, and from 40 to 49 in 9. In terms of gender, there were 62 men (86.11%) and 8 women (13.89%) with the triad injury. "O'Donoghue's Triad" was obtained during sports in 91.52% of cases, the remaining 8.48% in car accidents and household accidents. Conclusions: The results of the study establish and provide coaches, physiotherapists, orthopedists, scientists and educators with up-to-date data on the epidemiology of O'Donoghue's Triad, its incidence, age and sex characteristics and its distribution by sport.

Mantle cell lymphoma (MCL), representing 5% of cases, is an aggressive B-cell non-Hodgkin lymphoma. Rarely, it can spread to other areas. This case illustrates a unique occurrence of MCL involving the appendix, leading to obstructive symptoms. Additionally, its presentation as volvulus added complexity to diagnosis and treatment. A 72-year-old man with a history of MCL came to the ER with right lower quadrant abdominal pain and nausea for 7 days. A computed tomography scan showed a swirling sign, concerning for volvulus. The patient required emergent surgery for exploratory laparotomy. Intraoperatively, the patient was found to have an enlarged appendix measuring 16.5 cm in length and 5 cm in diameter. An appendectomy was performed, and the pathology was confirmed to be MCL. This is a rare case of MCL presenting in the appendix as a volvulus, resulting in obstructive symptoms. This distinctive manifestation posed significant challenges in diagnosis and management. Appreciating such cases is pivotal for accurate diagnosis and effective medical and surgical interventions for this aggressive lymphoma subtype. [ABSTRACT FROM AUTHOR]

IntroductionThe varus and valgus knee deformities result from imbalance in tension between medial and lateral soft tissue compartments. These conditions need to be addressed during total knee arthroplasty (TKA). However, there is no consensus on optimal soft-tissue release techniques for correcting varus and valgus deformities during TKA. We assessed the efficacy of a novel grid-based pie-crusting technique on soft-tissue release.MethodsCadaver knees were dissected, leaving only the femur and tibia connected by an isolated MCL or the femur and fibula connected by an isolated LCL. Bone cuts were made as performed during primary TKA. Mechanical testing was performed using an MTS machine. A 3D-printed 12-hole grid was placed directly over the MCL and LCL. Using an 18-gauge needle, horizontal in-out perforations were made 3 mm apart. Deformation and stiffness of the ligaments were collected after every 2 perforations. Means were calculated, and regression analyses were performed.ResultsA total of 7 MCL and 6 LCL knees were included in our analysis. The mean medial femorotibial (MFT) space increased from 6.018 ± 1.4 mm–7.078 ± 1.414 mm (R2 = 0.937) following 12 perforations. The mean MCL stiffness decreased from 32.15 N/mm–26.57 N/mm (R2 = 0.965). For the LCL group, the mean gap between the femur and fibula increased from 4.287 mm–4.550 mm following 8 perforations. The mean LCL stiffness decreased from 29.955 N/mm–25.851 N/mm. LCL stiffness displayed a strong inverse relationship with the number of holes performed (R2 = 0.988).DiscussionOur results suggest that using this novel grid for pie-crusting of the MCL and LCL allows for gradual lengthening of the ligaments without sacrificing their structural integrity. Our proposed technique may serve as a valuable piece in the soft-tissue release toolkit for orthopaedic surgeons performing TKA in varus and valgus deformed knees.

Resistance to antimalarial drugs leads a global recurrence of malaria, posing a significant challenge to malaria control. This study aimed to assess gene expression and resistance profiles in clinical isolates, and validate the inhibitory effect of MCL compound against PbAP2-I and PbBDP1 genes in vivo. Malaria prevalence rate throughout the clinical study period stood at 12.24%. Blood samples were obtained from 182 malaria outpatients and 30 P. berghei-infected mice treated with varying MCL concentrations. DNA and RNA were extracted. PfAP2-I, PfBDP1, PfMDR1, and PfK13 genes were amplified using Real-time qPCR and sequenced for mutation profiling. Relative gene expression of AP2-I and BDP1 genes in P. falciparum and P. berghei-treated mice was carried out by Reverse-transcription PCR. The data were analyzed using ANOVA at P

Background: Micheliolide (MCL), which is the active metabolite of parthenolide, has demonstrated promising clinical application potential. However, the effects and underlying mechanisms of MCL on atherosclerosis are still unclear. Method: ApoE−/− mice were fed with high fat diet, with or without MCL oral administration, then the plaque area, lipid deposition and collagen content were determined. In vitro, MCL was used to pretreat macrophages combined by ox-LDL, the levels of ferroptosis related proteins, NRF2 activation, mitochondrial function and oxidative stress were detected. Results: MCL administration significantly attenuated atherosclerotic plaque progress, which characteristics with decreased plaque area, less lipid deposition and increased collagen. Compared with HD group, the level of GPX4 and xCT in atherosclerotic root macrophages were increased in MCL group obviously. In vitro experiment demonstrated that MCL increased GPX4 and xCT level, improved mitochondrial function, attenuated oxidative stress and inhibited lipid peroxidation to suppress macrophage ferroptosis induced with ox-LDL. Moreover, MCL inhibited KEAP1/NRF2 complex formation and enhanced NRF2 nucleus translocation, while the protective effect of MCL on macrophage ferroptosis was abolished by NRF2 inhibition. Additionally, molecular docking suggests that MCL may bind to the Arg483 site of KEAP1, which also contributes to KEAP1/NRF2 binding. Furthermore, Transfection Arg483 (KEAP1-R483S) mutant plasmid can abrogate the anti-ferroptosis and anti-oxidative effects of MC in macrophages. KEAP1-R483S mutation also limited the protective effect of MCL on atherosclerosis progress and macrophage ferroptosis in ApoE−/− mice. Conclusion: MCL suppressed atherosclerosis by inhibiting macrophage ferroptosis via activating NRF2 pathway, the related mechanism is through binding to the Arg483 site of KEAP1 competitively.

Background: Multiligament knee injuries involving the medial side are common. When performing surgical reconstruction, use of the medial hamstrings (HS) as grafts remains controversial in this setting. Purpose: To determine the role of the medial HS in stabilizing the valgus knee for different types of medial-sided knee injury. Study Design: Controlled laboratory study. Methods: A biomechanical study on 10 cadaveric knees was performed. Valgus load (force moment of 10 N/m) was applied at 0°, 30°, and 60° of flexion, and the resultant rotation was recorded using an optoelectronic motion analysis system. Measurements were repeated for 4 different knee states: intact knee, superficial medial collateral ligament (sMCL) injury, deep medial collateral ligament (dMCL) injury, and posterior oblique ligament (POL) injury. For each state, 4 loading conditions (+ loaded; – unloaded) of the semitendinosus (ST) and gracilis (GRA) tendons were tested: ST+/GRA+, ST+/GRA–, ST–/GRA+, and ST–/GRA–. Results: At 0° of flexion, combined unloading of the ST and GRA (ST–/GRA–) increased valgus laxity on the intact knee compared with the ST+/GRA+ condition (P <.05). For all medial-sided injury states (isolated sMCL; combined sMCL and dMCL; and combined sMCL, dMCL, and POL damage), ST–/GRA– increased valgus laxity at 0° and 30° of flexion versus ST+/GRA+ (P <.05 for all). The absolute value of valgus laxity increased with the severity of medial-sided ligament injury. Isolated ST unloading increased valgus laxity for the intact knee and the MCL-injured knee (combined sMCL and dMCL) at 0° of flexion (P <.05 vs ST+/GRA+). Isolated unloading of the GRA had no effect on valgus knee stability. Conclusion: The medial HS tendons contributed to the stabilization of the knee in valgus, and this was even more important when the medial side was severely affected (POL damage). This stabilizing effect was greater between 0° and 30°, in which the POL is the main valgus stabilizer. Clinical Relevance: When deciding on graft selection for multiligament knee injury reconstruction, the surgeon should be aware of the effect of harvesting the medial HS tendon on valgus laxity. [ABSTRACT FROM AUTHOR]

Non-Hodgkin lymphoma's (NHL) incidence is rising over time, and B cell lymphomas comprise the majority of lymphomas. The phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue 1 (Akt)/mammalian target of the rapamycin (mTOR) signaling pathway plays a critical role in a variety of cellular processes, such as cell proliferation and survival. Its role in lymphomagenesis is confirmed in many different types of B cell lymphomas. This review is mainly focused on the PI3K/v-akt/mTOR pathway-related oncogenic mechanisms in B cell NHLs with an emphasis on common B cell lymphoma types [diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL)]. Furthermore, it summarizes the literature regarding the clinical applications of the mTOR inhibitors temsirolimus and everolimus in B cell NHLs, which have been tested in a range of clinical trials enrolling patients with B cell malignancies, either as monotherapy or in combination with other agents or regimens. [ABSTRACT FROM AUTHOR]

This report describes the identification and management of a Stener-like lesion of the medial collateral ligament of the knee in a 55-year-old woman. Patient underwent magnetic resonance imaging (MRI) following a skiing injury and was found to have a tear of the distal fibers of the superficial medial collateral ligament (MCL) complex, with displacement of the ligament superficial to the tendons inserting at the pes anserinus. Identification of a Stener-like lesion in the setting of MCL injury aids in selecting appropriate management. Prompt surgical intervention is warranted to achieve anatomic healing and prevent long-term valgus instability, chronic pain, and osteoarthritis.

Purpose: Ligament balancing is a prerequisite for good function and survival in total knee arthroplasty (TKA). Various balancing techniques exist, but none have shown superior results. The pie-crusting technique by Bellemans of the medial collateral ligament is commonly utilized; however, it can be difficult to achieve repeatable ligament lengthening with this technique. Therefore, we invented a novel instrument to standardize the pie-crusting technique of the superficial and deep medial collateral ligament (hereafter MCL). The purpose was to examine if pie-crusting with the instrument could produce repeatable ligament lengthening. Methods: The MCL was isolated in 16 human cadaveric knees, and subjected to axial tension. The instrument was composed of a specific grid of holes in rows, used to guide sequential pie-crusting puncturing of the MCL with a Ø1.6 mm end-cutting cannula. Ligament lengthening was measured after each row of punctures. Regression analysis was performed on the results. Results: Mean lengthening ± SD in human cadaveric MCL for puncturing of row 1 in the instrument was 0.06 ± 0.09 mm, 0.06 ± 0.04 mm for row 2, 0.09 ± 0.08 mm for row 3, 0.06 ± 0.05 mm for row 4 and 0.06 ± 0.04 mm for row 5, giving a mean total lengthening of 0.33 ± 0.20 mm. Linear regression revealed that MCLs were repeatably lengthened by 0.07 mm per row when punctured using the instrument. Conclusions: MCLs showed linear lengthening in human cadavers for subsequent use of the instrument. Our instrument shows promising results for repeatable ligament lengthening. [ABSTRACT FROM AUTHOR]

Despite major progress in mantle cell lymphoma (MCL) therapeutics, MCL remains a deadly disease with a median survival not exceeding four years. No single driver genetic lesion has been described to solely give rise to MCL. The hallmark translocation t(11;14)(q13;q32) requires additional genetic alterations for the malignant transformation. A short list of recurrently mutated genes including ATM, CCND1, UBR5, TP53, BIRC3, NOTCH1, NOTCH2, and TRAF2 recently emerged as contributors to the pathogenesis of MCL. Notably, NOTCH1 and NOTCH2 were found to be mutated in multiple B cell lymphomas, including 5–10% of MCL, with most of these mutations occurring within the PEST domain of the protein. The NOTCH genes play a critical role in the early and late phases of normal B cell differentiation. In MCL, mutations in the PEST domain stabilize NOTCH proteins, rendering them resistant to degradation, which subsequently results in the upregulation of genes involved in angiogenesis, cell cycle progression, and cell migration and adhesion. At the clinical level, mutated NOTCH genes are associated with aggressive features in MCL, such as the blastoid and pleomorphic variants, a shorter response to treatment, and inferior survival. In this article, we explore in detail the role of NOTCH signaling in MCL biology and the ongoing efforts toward targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Terrible triad of the elbow presents a rare combination of posterior elbow dislocation with a radial head fracture and the ulnar coronoid process fracture. Such injuries usually have variable outcomes. Case report: We report the case of a 44-year-old male who presented with a bilateral terrible triad of the elbow, occurring after a fall from height. We performed a surgical fixation of the radial head through a lateral approach on one side and an excision of the fractured fragment on the opposite side. A simultaneous repair of the lateral collateral ligament (LCL), medial collateral ligament (MCL), and coronoid was fixed bilaterally through an anteromedial incision. Three months after surgery, bone union was observed. The patient was able to resume his daily activities after five months of surgery with good functional outcomes. Conclusion: Precise surgical planning and rehabilitation can achieve good functional and clinical outcomes in terrible triad injuries with minimal use of implants.

Background: Chronic combined medial collateral ligament (MCL) and anterior cruciate ligament (ACL) injuries are frequent. Medial residual laxity is a risk factor for ACL rerupture. It should be treated at the same time as the ACL reconstruction (ACLR) if necessary, but there are still questions surrounding the indications for abstention or surgery of the medial plan, especially for grade 2 MCL injuries of the Fetto and Marshall classification. Indications: The purpose is to come back to a simple test, the "Rotatory Instability Test" as described by Slocum and Larson in 1968 for systematic clinical examination of the knee to improve the sensitivity and accuracy of the deep MCL (dMCL) and superficial MCL (sMCL) examination and to propose a decision-making algorithm for the treatment of the chronic combined ACL/MCL injuries based on the assessment of anteromedial rotatory instability (AMRI). Technique Description: Examination of the ACL with Lachman test, anterior drawer in neutral rotation, and pivot shift test confirm the ACL injury. Valgus laxity is tested in extension and at 20° of flexion. Then, an anterior drawer test at 90° of flexion with external rotation is done (the anterior drawer in external rotation [ADER] test) allowing to identify isolated dMCL, dMCL + sMCL, or MCL + posterior oblique ligament (POL) injuries. Discussion: As persistent medial laxity is a risk factor for ACL graft failure and there is no reliable method of instrumented laxity assessment, careful clinical examination remains essential. Systematic examination of the medial side with valgus laxity testing at 0° and 20° flexion combined with the ADER test assessment of AMRI can guide treatment of the MCL injury component. Where there is no valgus laxity and the ADER test is negative, isolated ACLR is indicated. If there is significant medial laxity at 0°, this suggests combining sMCL and POL reconstruction with ACLR. Where the knee is stable at 0° but there is valgus laxity at 20° and a positive ADER test, the dMCL can be reconstructed using a gracilis graft or a combined sMCL and dMCL reconstruction can be added to the ACLR depending on the degree of laxity. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication. Graphical Abstract This is a visual representation of the abstract. [ABSTRACT FROM AUTHOR]

Abstract Mantle cell lymphoma (MCL) is a rare B‐cell non‐Hodgkin lymphoma (NHL) that is aggressive and incurable with existing therapies, presenting a significant unmet clinical need. MCL occurs mainly in elderly patients with comorbidities; thus, intense treatment options including allogeneic stem cell transplantation (Allo‐SCT) are not feasible. New treatment options are emerging for this elderly/unfit treatment group, we therefore conducted a systematic review to determine whether they offered an advance on the existing recommended treatment, R‐CHOP. The search strategies to identify MCL therapies were designed to capture the most relevant studies from 2013 to 2020. Following preferred reporting items for systematic reviews and meta‐analyses and population,interventions, observations and study design analysis, R‐CHOP, ibrutinib and bendamustine plus rituximab (BR) were taken forward for critical and statistical analysis. All three therapies were effective in increasing the overall survival (OS) and progression‐free survival of elderly/unfit patients with MCL. However, none resulted in a significant increase in OS compared to R‐CHOP. In addition, R‐CHOP had a better toxicity profile when compared to both ibrutinib and BR. We therefore conclude that treatment of elderly/unfit patients with MCL is still a significant unmet clinical need; and suggest that outside of the clinical trial setting, R‐CHOP should remain the recommended front‐line treatment for this patient group.

Abstract Purpose Ligament balancing is a prerequisite for good function and survival in total knee arthroplasty (TKA). Various balancing techniques exist, but none have shown superior results. The pie‐crusting technique by Bellemans of the medial collateral ligament is commonly utilized; however, it can be difficult to achieve repeatable ligament lengthening with this technique. Therefore, we invented a novel instrument to standardize the pie‐crusting technique of the superficial and deep medial collateral ligament (hereafter MCL). The purpose was to examine if pie‐crusting with the instrument could produce repeatable ligament lengthening. Methods The MCL was isolated in 16 human cadaveric knees, and subjected to axial tension. The instrument was composed of a specific grid of holes in rows, used to guide sequential pie‐crusting puncturing of the MCL with a Ø1.6 mm end‐cutting cannula. Ligament lengthening was measured after each row of punctures. Regression analysis was performed on the results. Results Mean lengthening ± SD in human cadaveric MCL for puncturing of row 1 in the instrument was 0.06 ± 0.09 mm, 0.06 ± 0.04 mm for row 2, 0.09 ± 0.08 mm for row 3, 0.06 ± 0.05 mm for row 4 and 0.06 ± 0.04 mm for row 5, giving a mean total lengthening of 0.33 ± 0.20 mm. Linear regression revealed that MCLs were repeatably lengthened by 0.07 mm per row when punctured using the instrument. Conclusions MCLs showed linear lengthening in human cadavers for subsequent use of the instrument. Our instrument shows promising results for repeatable ligament lengthening.

Mantle cell lymphoma (MCL) with testicular involvement is a rare presentation and only a few cases have been described in the literature. We present a case of MCL with testicular involvement and the first analysis of all previously reported cases assessing trends in immunohistochemical features, prognostic indicators, and survival. Our data suggest that among all MCL, testicular MCL is more likely to present with aggressive features: blastoid/pleomorphic morphology, high Ki-67 proliferative index, and CNS involvement. Testicular MCL is also associated with shorter overall survival.

Background: The tibial collateral ligament, also known as the medial collateral ligament (MCL), is a ligament extending from the medial epicondyle of the femur to the posteromedial crest of the tibia. The ligament is a broad and strong band that mainly functions to stabilize the knee joint in the coronal plane on the medial side Since MCL calcification is not a frequent knee pain manifestation, exclusion of other confusing clinical mimicries is of paramount importance. Here, in this report, we describe a well-circumscribed calcific deposit in the left femoral condylar attachment of MCL reported very rarely in the medical literature. Case Report: A 37-year-old laborer presented to the Outpatient department with pain and flexion deformity of the Right knee for 6 months. He walked on a flexed knee with a limping gait. A plain radiograph of the right was taken in AP and Lateral view which showed a massive well-defined calcification at the medial side of the knee joint. Considering the large size of the lesion, surgical treatment was chosen. Intra-operatively, as the MCL was involved a reconstruction was done using the semitendinosus tendon. Conclusion: Chronic pain located at the medial side of the knee is not always osteoarthritic pain. Thorough clinical and radiological investigation with plain radiographs and MRI in some cases is mandatory. Calcification or ossification of the medial collateral ligament of the knee responds well to conservative treatment. Surgical resection is needed in some cases with larger lesions.

Cirmtuzumab may enhance the therapeutic activity of ibrutinib by inhibiting ROR1-dependent signaling pathway in patients with chronic lymphocytic leukemia (CLL). Mantle cell lymphoma (MCL) is B-cell malignancy that also expresses ROR1. In this study, we found that the plasma of patients with MCL had high levels of Wnt5a, a ROR1 ligand, that were comparable to those found in patients with CLL; in contrast Wnt5a was virtually undetectable in the plasma of age-matched healthy adults. We also found that Wnt5a induced Rac1 activation in the primary MCL cells. Cirmtuzumab, but not ibrutinib, could inhibit the capacity of Wnt5a to induce primary MCL cells to activate Rac1. Addition of exogenous Wnt5a in vitro significantly enhanced the numbers of MCL cell divisions and the proportion of dividing MCL cells entering S/G2 in MCL cells over time in the presence of CD154 and IL-4/10. Treatment of the MCL cells with cirmtuzumab, but not ibrutinib, blocked Wnt5a-enhanced proliferation of MCL cells. This study indicates that cirmtuzumab and ibrutinib may have complementary activity in the treatment of patients with MCL.

Background: The tibial collateral ligament, also known as the medial collateral ligament (MCL), is a ligament extending from the medial epicondyle of the femur to the posteromedial crest of the tibia. The ligament is a broad and strong band that mainly functions to stabilize the knee joint in the coronal plane on the medial side Since MCL calcification is not a frequent knee pain manifestation, exclusion of other confusing clinical mimicries is of paramount importance. Here, in this report, we describe a well-circumscribed calcific deposit in the left femoral condylar attachment of MCL reported very rarely in medical literature. Case report: A 37-year-old labourer presented to the Outpatient department with pain and flexion deformity of Right knee for 6 months. He walked on a flexed knee with a limping gait. Plain radiograph of the right was taken in AP and Lateral view which showed a massive well-defined calcification at the medial side of the knee joint. Considering the large size of the lesion, surgical treatment was chosen. Intra-operatively, as the MCL was involved a reconstruction was done using the semitendinosus tendon. Conclusion: Chronic pain located at the medial side of the knee is not always osteoarthritic pain. Thorough clinical and radiological investigation with plain radiographs and MRI in some cases is mandatory. Calcification or ossification of the medical collateral ligament of the knee responds well to conservative treatment. Surgical resection is needed in some cases with larger lesions.

The receptor tyrosine kinase orphan receptor 1 (ROR1) is absent in most normal adult tissues but overexpressed in various malignancies and is of importance for tumor cell survival, proliferation, and metastasis. In this study, we evaluated the apoptotic effects of a novel small molecule inhibitor of ROR1 (KAN0441571C) as well as venetoclax (BCL-2 inhibitor), bendamustine, idelalisib (PI3Kδ inhibitor), everolimus (mTOR inhibitor), and ibrutinib (BTK inhibitor) alone or in combination in human MCL primary cells and cell lines. ROR1 expression was evaluated by flow cytometry and Western blot (WB). Cytotoxicity was analyzed by MTT and apoptosis by Annexin V/PI staining as well as signaling and apoptotic proteins (WB). ROR1 was expressed both in patient-derived MCL cells and human MCL cell lines. KAN0441571C alone induced significant time- and dose-dependent apoptosis of MCL cells. Apoptosis was accompanied by decreased expression of MCL-1 and BCL-2 and cleavage of PARP and caspase 3. ROR1 was dephosphorylated as well as ROR1-associated signaling pathway molecules, including the non-canonical WNT signaling pathway (PI3Kδ/AKT/mTOR). The combination of KAN0441571C and ibrutinib, venetoclax, idelalisib, everolimus, or bendamustine had a synergistic apoptotic effect and significantly prevented phosphorylation of ROR1-associated signaling molecules as compared to KAN0441571C alone. Our results suggest that targeting ROR1 by a small molecule inhibitor, KAN0441571C, should be further evaluated particularly in combination with other targeting drugs as a new therapeutic approach for MCL. [ABSTRACT FROM AUTHOR]

Multi ligament knee injuries (MLKIs) are highly complex injuries with associated complications and often present with difficult management strategies. MLKIs may affect the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (or posteromedial corner (PMC)), and lateral collateral ligament (or posterolateral corner (PLC)) in addition to other structures including the menisci, common peroneal nerve, and popliteal artery. MLKIs are highly associated with the male sex and are commonly seen in high-velocity motor vehicle accidents and low-velocity sports injuries. Given the multiple planes of movement in the knee and various primary and secondary stabilizers throughout those planes, there is great heterogeneity in an injury pattern and most involve the ACL and PCL. Initial evaluation of this injury includes assessment of lower extremity sensation, distal pulses, and ankle-brachial index (ABI). If vascular compromise is suspected, computed tomography angiography (CTA) or magnetic resonance angiography (MRA) are indicated to evaluate the vasculature. As opposed to CTA, MRA offers visualization of the soft-tissue structures that are commonly damaged in MLKIs. Initial management typically includes closed reduction of the knee with subsequent external fixation. Classification systems guide initial assessments; however, further management is unclear and leads the surgical team to decide the best, individualized management option for each patient. As a result, optimal surgical and postoperative treatment options remain complicated, and clinical outcomes remain difficult to predict. The purpose of this review is to consolidate the most up-to-date practices of the diagnostic workup, management, and treatment of MLKIs. [ABSTRACT FROM AUTHOR]

An expert panel convened by the European Alliance for Personalized Medicine (EAPM) reflected on achievements and outstanding challenges in Europe in mantle cell lymphoma (MCL). Through the prism of member state experience, the panel noted advances in outcomes over the last decade, but highlighted issues constituting barriers to better care. The list notably included availability of newer treatments, infrastructure and funding for related testing, and shortages of relevant skills and of research support. The prospect of improvements was held to reside in closer coordination and cooperation within and between individual countries, and in changes in policy and scale of investment at both national and EU levels. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that Kaplan fibers (KFs) play a role in controlling anterolateral rotatory knee laxity in anterior cruciate ligament (ACL) injury. However, recent clinical studies have suggested that KF injuries are not associated with a higher-grade pivot shift in knees with acute ACL injuries., Purpose: To compare the effect of KF and anterolateral ligament injury on anterolateral rotatory laxity as measured by the pivot-shift test in both adult and adolescent patients with acute ACL injury., Study Design: Cross-sectional study; Level of evidence, 3., Methods: This study consisted of patients who experienced primary acute ACL tears between January 2019 and December 2021. The magnetic resonance imaging examinations and pivot-shift tests for these individuals were conducted within 14 days after injury. Variables associated with concomitant injury were included in a binary logistic regression model to evaluate risk factors of a high-grade pivot shift and a KF injury., Results: The study included 540 patients with acute ACL tears (64 adolescent patients and 476 adults). The main risk factor for a high-grade pivot shift after acute ACL injury in adults was partial or total disruption of anterolateral ligament continuity (odds ratio [OR], 2.271; 95% CI, 1.499-3.442). In adolescent patients, the main risk factor was KF injury (OR, 19.98; 95% CI, 2.367-168.669), including edema and disruption of continuity., Conclusion: The main risk factor for a high-grade pivot shift after acute ACL injury differs between adolescent patients and adults: the KF injury sign in adolescent patients indicates a higher-grade pivot shift., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was supported by the Scientific Research Program of Sichuan Medical and Health Care Promotion Institute (KY2022SJ0396) and Research Program of Sichuan Medical Association (Q22085). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Objectives: Medial collateral ligament "pie-crusting" (MCLPC), selective release of the superficial MCL, has been shown to improve the arthroscopic access to the posterior horn of the medial meniscus without adversely affecting the outcomes of isolated meniscal surgery. However, whether MCL PC, to address concomitant meniscal lesions during anterior cruciate ligament reconstruction (ACLR) surgery, adversely affects ACLR outcomes is unknown. The aim of this study was to assess whether patients who had undergone MCLPC at the time of ACLR had similar post outcomes to patients undergoing isolated ACLR., Methods: 55 consecutive patients (33 male and 22 female), with minimum 2-year follow-up, who had undergone MCLPC with concomitant primary ACLR (PC group) were retrospectively matched on the basis of age, sex and follow-up with 55 patients who underwent isolated primary ACLR. Post-operative outcome measures (PROMs) included the Knee injury and Osteoarthritis Outcome Score, the International Knee Documentation Committee score, Tegner activity score, the EuroQol five-dimension health questionnaire and EuroQol visual analogue scale., Results: The two groups' median postoperative EQ 5D-VAS, EQ 5D-index and Tegner scores were similar. The difference between pre-operative and post-operative KOOS scores was similar for the two group for all subscales except the ADL subscale which was higher in the MCLPC group (24, IQR= 6-32) than in the isolated ACLR group (5, IQR= 0-9.74). The median post op IKDC score was 84 in the MCLPC group and compared with 90 in the isolated ACLR group. However, the difference between pre-operative and post-operative IKDC scores was higher in patients in the MCLPC group (40, IQR= 25-49) than in the isolated ACLR group (32, IQR=19.6-46.8)., Conclusions: MCLPC, performed at the time of ACLR does not appear to adversely affect the functional post-operative outcomes., Level of Evidence: IV., Competing Interests: Declaration of Competing Interest ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:James Robinson reports a relationship with Smith and Nephew Inc that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. James Robinson reports a relationship with CONMED Corporation that includes: speaking and lecture fees and travel reimbursement. James Robinson reports a relationship with Newclip Technics that includes: speaking and lecture fees and travel reimbursement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Multi-ligament knee injury, involving complex destruction of structures like the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL), presents significant challenges in treatment as well as diagnosis. This case study focuses on a 55-year-old woman who was the victim of a severe traffic accident and had an ACL and PCL avulsion fracture, a medial condyle fracture, and a medial collateral ligament rupture. Afterward, open reduction and internal fixation of the right tibial plateau surgery was performed after a delay in order to manage the pain and swelling. Her rehabilitation was greatly helped by postoperative physical therapy, which focused on pain control, early mobilization, and gradual strength development. A well-structured rehabilitation plan was found to be beneficial, as indicated by the remarkable improvements in pain reduction and functional mobility. This case highlights the value of effective physical therapy in helping patients through the difficult recovery process following multiple ligament injuries with the goal of restoring function and improving their quality of life., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Thamke et al.)

Compared with the large number of single-function materials such as aggregation-induced emission (AIE), mechanochromic luminescence (MCL), or thermally activated delayed fluorescence (TADF) emitters, multifunctional emitting materials offer more opportunities in practical applications. In this report, we provide a simple molecular design strategy towards the conversion of a MCL building block to a multifunctional emitter. Through altering the substituent sites and increasing the number of electron donors and steric hindrance on a normal MCL backbone benzo[d,e]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one, a novel multifunctional material 10,11-bis-(4-diphenylamino-phenyl)-benzo[d,e]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one (10,11-2TPA-BBI) is designed and synthesized. 10,11-2TPA-BBI exhibits simultaneous polymorphism, AIE, MCL and TADF properties. It can form four different aggregate species: yellow solid (YS) and orange solid (OS), orange flake-shaped crystal (OC), and red prism-like crystal (RC). Among them, because of the small energy gaps (ΔESTs < 0.3 eV) between the singlet and triplet excited states, OS, OC and RC exhibit TADF properties, while YS show normal fluorescence characteristics with a large ΔEST of 0.33 eV. OS can be reversibly transformed into YS upon external stimuli, which can be attributed to the emission switch between local excited state and charge transfer state. Crystallographic study indicates that the bulky structure and weak intermolecular interactions account for polymorphism and AIE properties. This work will provide a simple molecular design strategy for multifunctional materials.

For autonomous navigation, we have thus far proposed MCL using environmental maps based on cadastral data. However, buildings in the cadastral data sometimes differ from their actual positions in the environment. As the environmental map is generated from the cadastral data, the inconsistency affects the localization performance. For this problem, we propose an online SLAM approach in the actual environment. A mobile robot simultaneously localizes the position and builds another online map using NDT scan matching. In contrast to other offline SLAM approaches, however, pose graph optimization for loop closure is not executed during online SLAM. As a result, the online map is distorted by localization errors. For this challenge inherent in online SLAM, the localization errors are modified using MCL and wheel odometry in a hybrid manner. As a contribution to autonomous navigation, the robot is enabled to localize the position even in a new place. In the experiments, we show that the localization performance of the robot in an outdoor environment with inconsistent buildings is improved compared to other online approaches with and without modifications. [ABSTRACT FROM AUTHOR]

Abstract Background To investigate the effect of complete rupture of the posterior cruciate ligament (PCL) on the biomechanics and histology of the medial collateral ligament (MCL). Materials and methods Seventy-two male rabbits were randomly divided into two groups: the ruptured group was treated with complete PCL amputation, while the intact group was only subjected to PCL exposure without amputation. Eighteen rabbits were randomly sacrificed at 8, 16, 24, and 40 weeks after the operation, and their specimens were processed for mechanical tensile testing, nano-indentation experiments, hematoxylin-eosin (HE) staining, and picrosirius-polarization staining. Results There was no significant difference in the length and maximum displacement of the MCL between the ruptured group and the intact group at each time point. The maximum load of the ruptured group was significantly smaller than that of the intact group at 40 W. The elastic modulus and micro-hardness of the ruptured group increased significantly at 24 W and decreased significantly at 40 W. At 16 W and 24 W after PCL rupture, the number of type I collagen fibers and type III collagen fibers in the MCL of the ruptured group was significantly increased compared with that of the intact group. While the type I collagen fibers of the ruptured group were significantly decreased compared with the intact group at 40 W, there was no significant difference in type III collagen fibers between the ruptured group and the intact group. Conclusion PCL rupture has no significant effect on the mechanical and histological properties of MCL in a short period of time under physiological loading, but the histological and mechanical properties of MCL decrease with time.

• miRNAs, lncRNAs, and circRNAs play critical functions in molecular mechanisms and signaling pathways in tumorigenesis. • Noncoding RNAs (ncRNAs) regulate the proliferation, metastasis, and invasion of B-cell non-Hodgkins lymphomas. • ncRNA dysregulations in B-cell lymphoma provide important insights into lymphoma's molecular pathogenesis. • miRNAs, lncRNAs, and circRNAs have been proposed as potential biomarkers for diagnosis, prognosis, and prediction of treatment response. B-cell non-Hodgkins lymphomas (BCNHLs) are a category of B-cell cancers that show heterogeneity. These blood disorders are derived from different levels of B–cell maturity. Among NHL cases, ∼80–90 % are derived from B-cells. Recent studies have demonstrated that noncoding RNAs (ncRNAs) contribute to almost all parts of mechanisms and are essential in tumorigenesis, including B-cell non-Hodgkins lymphomas. The study of ncRNA dysregulations in B-cell lymphoma unravels important mysteries in lymphoma's molecular etiology. It seems also necessary for discovering novel trials as well as investigating the potential of ncRNAs as markers for their diagnosis and prognosis. In the current study, we summarize the role of ncRNAs involving miRNAs, long noncoding RNAs, as well as circular RNAs in the development or progression of BCNHLs. [ABSTRACT FROM AUTHOR]

Simple Summary: Lymphoma involving the central nervous system and CNS relapse present diagnostic and predictive challenges. Its diagnosis is based on conventional methods with low sensitivity and/or specificity. More powerful tools for its early detection, response evaluation, and CNS relapse prediction are needed. MicroRNAs are short post-transcriptional gene regulators that are remarkably stable and detectable extracellularly in body fluids. We evaluated the diagnostic and predictive potential of circulating oncogenic microRNAs (oncomiRs) in CSF and plasma for the detection of secondary CNS involvement in aggressive B-NHL lymphomas, as well as for detection and prediction of their CNS relapse. Our findings indicate that the evaluation of oncogenic microRNAs in CSF and plasma potentially provides a sensitive tool for the early detection of secondary CNS lymphoma, the monitoring and estimating of treatment efficacy, and the prediction and early detection of CNS relapse. Lymphoma with secondary central nervous system (CNS) involvement represents one of the most aggressive malignancies, with poor prognosis and high mortality. New diagnostic tools for its early detection, response evaluation, and CNS relapse prediction are needed. We analyzed circulating microRNAs in the cerebrospinal fluid (CSF) and plasma of 162 patients with aggressive B-cell non-Hodgkin's lymphomas (B-NHL) and compared their levels in CNS-involving lymphomas versus in systemic lymphomas, at diagnosis and during treatment and CNS relapse. We identified a set of five oncogenic microRNAs (miR-19a, miR-20a, miR-21, miR-92a, and miR-155) in CSF that detect, with high sensitivity, secondary CNS lymphoma involvement in aggressive B-NHL, including DLBCL, MCL, and Burkitt lymphoma. Their combination into an oncomiR index enables the separation of CNS lymphomas from systemic lymphomas or nonmalignant controls with high sensitivity and specificity, and high Receiver Operating Characteristics (DLBCL AUC = 0.96, MCL = 0.93, BL = 1.0). Longitudinal analysis showed that oncomiR levels reflect treatment efficacy and clinical outcomes, allowing their monitoring and prediction. In contrast to conventional methods, CSF oncomiRs enable detection of early and residual CNS involvement, as well as parenchymal involvement. These circulating oncomiRs increase 1–4 months before CNS relapse, allowing its early detection and improving the prediction of CNS relapse risk in DLBCL. Similar effects were detectable, to a lesser extent, in plasma. [ABSTRACT FROM AUTHOR]

Among all image enhancement techniques, histogram equalization is the most used technique. However, preserving brightness is the main issue, and it creates a weird look by destroying its originality. This paper proposes a new method that has command on the brightness issue of histogram equalization to enhance the quality of microscopic images. The method splits the histogram of each color channel into two sub-histograms based on their mean as the threshold and supplanting their cumulative distribution with Kumaraswamy distribution. The proposed method is tested with color microscopic images of cancer-affected lymph nodes gathered from Biological Image Repository IICBU, and objective and subjective assessments confirm that the proposed approach performs more efficiently compared to other state-of-the-art methods. [ABSTRACT FROM AUTHOR]

This article provides a thorough description of a range of non-standard application cases in which EMC laboratories can be used other than those traditionally associated with this kind of facilities. The areas covered here include investigations of: wireless and radio systems (such as IoT and broadband radio systems) also that require ultra-high operational dynamic range, emulation of interference-free and/or heavilymultipath propagation environment, shielding effectiveness of cabinets and materials (i.e. thin, light and flexible as textiles as well as heavy and thick such as building construction elements).

Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for treatment of relapsed/refractory mantle cell lymphoma (MCL). During a fludarabine shortage, we used bendamustine as an alternative to standard cyclophosphamide/fludarabine (cy/flu) lymphodepletion (LD) prior to brexu-cel. We assessed MCL patient outcomes as well as CAR T-cell expansion and persistence after brexu-cel following bendamustine or cy/flu LD at our center. This was a retrospective single institution study that utilized prospectively banked blood and tissue samples. Clinical efficacy was assessed by 2014 Lugano guidelines. CAR T-cell expansion and persistence in peripheral blood were assessed on day 7 and at ≥month 6 for patients with available samples. Seventeen patients received bendamustine and 5 received cy/flu. For the bendamustine cohort, 14 (82%) received bridging therapy and 4 (24%) had CNS involvement. Fifteen patients (88%) developed CRS with 4 (24%) ≥grade 3 events. Six (35%) patients developed ICANS with 4 (24%) events ≥grade 3. No patient had ≥grade 3 cytopenias at day 90. Best objective (BOR) and complete response (CRR) rates were 82% and 65%, respectively. At 24.5 months median follow-up, 12-month progression-free survival (PFS) was 45%, 24-month PFS was 25%, and median duration of response was 19 months. Median OS was not reached. BOR was 25% (1/4) for patients with CNS involvement. CAR transgene expansion after bendamustine LD was observed on day 7 in all (4/4) patients tested and persisted at ≥6 months (2/2), regardless of response. Bendamustine LD before brexu-cel for MCL is feasible and safe with a lower frequency and shorter duration of cytopenias than reported for cy/flu. Both CAR T-cell expansion and persistence were observed after bendamustine LD. Outcomes appear comparable to the real world outcomes reported with cy/flu LD., (Copyright © 2024. Published by Elsevier Inc.)

Purpose : Anterior cruciate ligament (ACL) injuries are often combined with lesions of the medial collateral ligament (MCL). The aim of this study was to evaluate treatment outcome of combined acute ACL and MCL lesions using functional US and clinical examination. Methods: Patients aged > 18 years undergoing primary ACL reconstruction with concomitant operative (group 1) or non-operative treatment of the MCL (group 2) between 2014 and 2019 were included after a minimum follow-up of 12 months. Grade II MCL injuries with dislocated tibial or femoral avulsions and grade III MCL ruptures underwent ligament repair whereas grade II injuries without dislocated avulsions were treated non-operatively. Radiological outcome was assessed with functional US examinations. Medial knee joint width was determined in a supine position at 0° and 30° of knee flexion in unloaded and standardized loaded (= 15 Dekanewton) conditions using a fixation device. Clinical examination was performed and patient-reported outcomes were assessed by the use of the subjective knee form (IKDC), Lysholm score, and the Tegner activity scale. Results: A total of 40 patients (20 per group) met inclusion criteria. Mean age of group 1 was 40 ± 12 years (60% female) with a mean follow-up of 33 ± 17 months. Group 2 showed a mean age of 33 ± 8 years (20% female) with a mean follow-up of 34 ± 15 months. Side-to-side differences in US examinations were 0.4 ± 1.5 mm (mm) in 0° and 0.4 ± 1.5 mm in 30° knee flexion in group 1, and 0.9 ± 1.1 mm in 0° and 0.5 ± 1.4 mm in 30° knee flexion in group 2, with no statistically significant differences between both groups. MCL repair resulted in lower Lysholm scores (75 ± 19 versus 86 ± 15; p < 0.05). No significant differences could be found for subjective IKDC or Tegner activity scores among the two groups. Conclusion: A differentiated treatment concept in combined ACL and MCL injuries based on injury patterns leads to reliable postoperative ligamentous knee stability in US-based and clinical examinations. However, grade II and III MCL lesions with subsequent operative MCL repair (group 1) result in slightly poorer subjective outcome scores. Level of evidence: Retrospective cohort study; Level III [ABSTRACT FROM AUTHOR]

The receptor tyrosine kinase orphan receptor 1 (ROR1) is absent in most normal adult tissues but overexpressed in various malignancies and is of importance for tumor cell survival, proliferation, and metastasis. In this study, we evaluated the apoptotic effects of a novel small molecule inhibitor of ROR1 (KAN0441571C) as well as venetoclax (BCL-2 inhibitor), bendamustine, idelalisib (PI3Kδ inhibitor), everolimus (mTOR inhibitor), and ibrutinib (BTK inhibitor) alone or in combination in human MCL primary cells and cell lines. ROR1 expression was evaluated by flow cytometry and Western blot (WB). Cytotoxicity was analyzed by MTT and apoptosis by Annexin V/PI staining as well as signaling and apoptotic proteins (WB). ROR1 was expressed both in patient-derived MCL cells and human MCL cell lines. KAN0441571C alone induced significant time- and dose-dependent apoptosis of MCL cells. Apoptosis was accompanied by decreased expression of MCL-1 and BCL-2 and cleavage of PARP and caspase 3. ROR1 was dephosphorylated as well as ROR1-associated signaling pathway molecules, including the non-canonical WNT signaling pathway (PI3Kδ/AKT/mTOR). The combination of KAN0441571C and ibrutinib, venetoclax, idelalisib, everolimus, or bendamustine had a synergistic apoptotic effect and significantly prevented phosphorylation of ROR1-associated signaling molecules as compared to KAN0441571C alone. Our results suggest that targeting ROR1 by a small molecule inhibitor, KAN0441571C, should be further evaluated particularly in combination with other targeting drugs as a new therapeutic approach for MCL.

Abstract Background A subset of diffuse large B-cell lymphoma may show aberrant cyclin D1 expression, which may be confused with blastoid mantle cell lymphoma. These cases usually lack of CCND1 gene rearrangement. Duplication of CCND1 gene was attributed to some of the cases with cyclin D1 expression. The mechanism of overexpression of CCND1 in other cases was not well documented. Case presentation We report a case of diffuse large B-cell lymphoma with cyclin D1 expression. The underlying mechanism for cyclin D1 expression was due to an abnormal gene rearrangement involving BCL-6 and CCND1, which was different from most reported cases. Rare cases with similar genetic profile were reported and were classified as diffuse large B-cell lymphoma. Conclusion The phenotype and genetic abnormalities of DLBCL with cyclin D1 overexpression can be complex and may be difficult to differentiate from blastoid and pleomorphic variants of mantle cell lymphoma.

Background: To investigate the effect of complete rupture of the posterior cruciate ligament (PCL) on the biomechanics and histology of the medial collateral ligament (MCL). Materials and methods: Seventy-two male rabbits were randomly divided into two groups: the ruptured group was treated with complete PCL amputation, while the intact group was only subjected to PCL exposure without amputation. Eighteen rabbits were randomly sacrificed at 8, 16, 24, and 40 weeks after the operation, and their specimens were processed for mechanical tensile testing, nano-indentation experiments, hematoxylin-eosin (HE) staining, and picrosirius-polarization staining. Results: There was no significant difference in the length and maximum displacement of the MCL between the ruptured group and the intact group at each time point. The maximum load of the ruptured group was significantly smaller than that of the intact group at 40 W. The elastic modulus and micro-hardness of the ruptured group increased significantly at 24 W and decreased significantly at 40 W. At 16 W and 24 W after PCL rupture, the number of type I collagen fibers and type III collagen fibers in the MCL of the ruptured group was significantly increased compared with that of the intact group. While the type I collagen fibers of the ruptured group were significantly decreased compared with the intact group at 40 W, there was no significant difference in type III collagen fibers between the ruptured group and the intact group. Conclusion: PCL rupture has no significant effect on the mechanical and histological properties of MCL in a short period of time under physiological loading, but the histological and mechanical properties of MCL decrease with time. [ABSTRACT FROM AUTHOR]

Background: Lesions of the medial collateral ligament (MCL) are the most common knee ligament injuries and, when they occur in isolation, they often progress with satisfactory outcomes using conservative treatment. However, MCL lesions associated with anterior cruciate ligament or posterior cruciate ligament (PCL) injuries in knee dislocations should be reconstructed to prevent failure of the central pivot. In knees with combined injuries involving the PCL and the MCL, the confluence of tunnels in the medial femoral condyle can be a potential problem during reconstruction surgery. Indications: The indication of this technique is the combined injury of the PCL and the MCL. Technique Description: The technique consists in the reconstruction of the PCL and the MCL with an Achilles tendon allograft. The bone plug of the graft is fixed on the tibial bed with the inlay technique. The graft passes through a single femoral tunnel drilled in the medial femoral condyle, with entrance point on the footprint of the PCL on the inner wall of the condyle and exit on the origin of the native MCL, near to the medial epicondyle. The graft is fixed in the femoral tunnel with an interference screw and continues to the isometric point of the anatomic insertion of the MCL in the tibia, where an interference screw is used to fix it. Results: Results from our group using this technique have shown good clinical outcomes, with complications and failure rates similar to other series in the literature. Discussion/Conclusion: This technique is an excellent option for surgeons, when an Achilles tendon allograft is available, to avoid confluence of tunnels in the medial femoral condyle. It presents good results and acceptable complication rates, compatible with the severity of this lesion. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication. Graphical Abstract This is a visual representation of the abstract. [ABSTRACT FROM AUTHOR]

Abstract Purpose Anterior cruciate ligament (ACL) injuries are often combined with lesions of the medial collateral ligament (MCL). The aim of this study was to evaluate treatment outcome of combined acute ACL and MCL lesions using functional US and clinical examination. Methods Patients aged > 18 years undergoing primary ACL reconstruction with concomitant operative (group 1) or non‐operative treatment of the MCL (group 2) between 2014 and 2019 were included after a minimum follow‐up of 12 months. Grade II MCL injuries with dislocated tibial or femoral avulsions and grade III MCL ruptures underwent ligament repair whereas grade II injuries without dislocated avulsions were treated non‐operatively. Radiological outcome was assessed with functional US examinations. Medial knee joint width was determined in a supine position at 0° and 30° of knee flexion in unloaded and standardized loaded (= 15 Dekanewton) conditions using a fixation device. Clinical examination was performed and patient‐reported outcomes were assessed by the use of the subjective knee form (IKDC), Lysholm score, and the Tegner activity scale. Results A total of 40 patients (20 per group) met inclusion criteria. Mean age of group 1 was 40 ± 12 years (60% female) with a mean follow‐up of 33 ± 17 months. Group 2 showed a mean age of 33 ± 8 years (20% female) with a mean follow‐up of 34 ± 15 months. Side‐to‐side differences in US examinations were 0.4 ± 1.5 mm (mm) in 0° and 0.4 ± 1.5 mm in 30° knee flexion in group 1, and 0.9 ± 1.1 mm in 0° and 0.5 ± 1.4 mm in 30° knee flexion in group 2, with no statistically significant differences between both groups. MCL repair resulted in lower Lysholm scores (75 ± 19 versus 86 ± 15; p

Introduction: The varus and valgus knee deformities result from imbalance in tension between medial and lateral soft tissue compartments. These conditions need to be addressed during total knee arthroplasty (TKA). However, there is no consensus on optimal soft-tissue release techniques for correcting varus and valgus deformities during TKA. We assessed the efficacy of a novel grid-based pie-crusting technique on soft-tissue release., Methods: Cadaver knees were dissected, leaving only the femur and tibia connected by an isolated MCL or the femur and fibula connected by an isolated LCL. Bone cuts were made as performed during primary TKA. Mechanical testing was performed using an MTS machine. A 3D-printed 12-hole grid was placed directly over the MCL and LCL. Using an 18-gauge needle, horizontal in-out perforations were made 3 mm apart. Deformation and stiffness of the ligaments were collected after every 2 perforations. Means were calculated, and regression analyses were performed., Results: A total of 7 MCL and 6 LCL knees were included in our analysis. The mean medial femorotibial (MFT) space increased from 6.018 ± 1.4 mm-7.078 ± 1.414 mm ( R = 0.937) following 12 perforations. The mean MCL stiffness decreased from 32.15 N/mm-26.57 N/mm ( 2  = 0.937) following 12 perforations. The mean MCL stiffness decreased from 32.15 N/mm-26.57 N/mm ( R 2  = 0.965). For the LCL group, the mean gap between the femur and fibula increased from 4.287 mm-4.550 mm following 8 perforations. The mean LCL stiffness decreased from 29.955 N/mm-25.851 N/mm. LCL stiffness displayed a strong inverse relationship with the number of holes performed ( R 2  = 0.988)., Discussion: Our results suggest that using this novel grid for pie-crusting of the MCL and LCL allows for gradual lengthening of the ligaments without sacrificing their structural integrity. Our proposed technique may serve as a valuable piece in the soft-tissue release toolkit for orthopaedic surgeons performing TKA in varus and valgus deformed knees., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Rezaei, Moon, Lichtig, Mera, Drake, Choubey, Kim, Tueni, Piponov, Koh, Karam and Amirouche.)