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.

OBJECTIVE: To compare rates of revisions between patients with isolated anterior cruciate ligament (ACL) reconstruction and those who had concomitant medial collateral ligament (MCL) injuries managed either operatively or nonoperatively at the time of index anterior cruciate ligament reconstruction (ACLR).
METHODS: Using laterality-specific International Classification of Diseases, Tenth Revision (ICD-10) and Current Procedural Terminology (CPT) codes, we queried the PearlDiver-Mariner Database for all patients who underwent ACLR between 2016 and 2020. Patients were included if they were ages 15 or older and had a minimum of 2 years of follow-up after index ACLR. Patients were then divided into cohorts by presence or absence of concomitant MCL injury. The cohort of concomitant MCL injuries was further subdivided into those with MCL injuries managed nonoperatively, with MCL repair, or with MCL reconstruction at the time of index ACLR. Multivariate regression was performed between cohorts to evaluate for factors associated with revision ACLR.
RESULTS: We identified 47,306 patients with isolated ACL injuries and 10,846 with concomitant MCL and ACL injuries. In total, 93% of patients with concomitant MCL injuries had their MCL treated nonoperatively; however, the annual proportion of patients being surgically managed for their MCL injury increased by 70% from 2016 to 2020. Concomitant MCL injury patients had greater odds of undergoing revision ACLR compared with patients with isolated ACL injuries (odds ratio 1.50, 95% confidence interval 1.36-1.66, P < .001). Among patients with concomitant MCL injuries, surgically managed patients had a greater risk of revision ACLR compared with nonoperatively managed MCL injuries (odds ratio 1.39, 95% confidence interval 1.01-1.86, P = .034).
CONCLUSIONS: Despite an increase in operatively managed concomitant MCL injuries, most concomitant MCL injuries were still managed nonoperatively at the time of ACLR. Patients with concomitant MCL injuries, particularly those managed operatively, at the time of ACLR are at increased risk of requiring revision ACLR compared with those with isolated ACL injuries.
METHODS: Level III, retrospective comparative case series.

The sterile alpha motif and histidine-aspartate (HD) domain containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate triphosphohydrolase with ara-CTPase activity that confers cytarabine (ara-C) resistance in several haematological malignancies. Targeting SAMHD1\'s ara-CTPase activity has recently been demonstrated to enhance ara-C efficacy in acute myeloid leukemia. Here, we identify the transcription factor SRY-related HMG-box containing protein 11 (SOX11) as a novel direct binding partner and first known endogenous inhibitor of SAMHD1. SOX11 is aberrantly expressed not only in mantle cell lymphoma (MCL), but also in some Burkitt lymphomas. Co-immunoprecipitation of SOX11 followed by mass spectrometry in MCL cell lines identified SAMHD1 as the top SOX11 interaction partner which was validated by proximity ligation assay. In vitro, SAMHD1 bound to the HMG box of SOX11 with low-micromolar affinity. In situ crosslinking studies further indicated that SOX11-SAMHD1 binding resulted in a reduced tetramerization of SAMHD1. Functionally, expression of SOX11 inhibited SAMHD1 ara-CTPase activity in a dose-dependent manner resulting in ara-C sensitization in cell lines and in a SOX11-inducible mouse model of MCL. In SOX11-negative MCL, SOX11-mediated ara-CTPase inhibition could be mimicked by adding the recently identified SAMHD1 inhibitor hydroxyurea. Taken together, our results identify SOX11 as a novel SAMHD1 interaction partner and its first known endogenous inhibitor with potentially important implications for clinical therapy stratification.

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).

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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 (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).
UNASSIGNED: 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.

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.

With the approval of the first CAR T-cell products for hematological malignancies in 2017, these autologous cell therapies have changed the treatment paradigm for patients with relapsed or refractory (r/r) non-Hodgkin lymphoma (NHL), who have a poor prognosis and few effective treatment options. Despite the demonstrated clinical benefit in patients with r/r diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma, many patients who are eligible for CAR T-cell therapies do not receive them or are treated with CAR T cells as a later line of therapy at advanced stages of disease. Several barriers exist for referring patients to an authorized treatment center (ATC) for CAR T-cell therapy. Although most patients with NHL are treated by community-based oncologists, educational gaps may exist for some community oncologists about the availability of CAR T-cell therapies in certain indications, the overall treatment process, and how they can access these therapies for their patients. In addition to navigation of the referral process from the community setting to the ATC, other barriers include timely identification of candidates eligible for CAR T-cell therapy and logistical and reimbursement concerns. Here, we examine the patient CAR T-cell experience, which begins and ends in the community setting, and identify and discuss opportunities for improved collaboration between community oncologists and ATC physicians to help address barriers to treatment and enhance patient outcomes. Treatment decisions for a patient\'s second or third line of therapy for NHL are critically important, owing to declining probabilities for favorable outcomes with each successive line of therapy. For patients who are eligible, CAR T-cell therapies should be considered as early as possible in their treatment course. A better understanding of the CAR T-cell process, the patient\'s experience, and the collaboration necessary for timely patient identification, better access, and successful outcomes will enable more patients to benefit from CAR T-cell therapies.

UNASSIGNED: Anteromedial rotatory instability (AMRI) of the knee is a complex and severe condition caused by injury to the anterior cruciate ligament and/or the medial collateral ligament. Clinical studies dealing with AMRI are rare, and objective measurements are nonexistent.
UNASSIGNED: The objectives of this study were, first, to quantify anteromedial rotatory knee laxity in healthy individuals using a noninvasive image analysis software and, second, to assess intra- and interrater reliability and equivalence in measuring anteromedial knee translation (AMT). It was hypothesized that AMT could be reliably quantified using a noninvasive image analysis software.
UNASSIGNED: Cohort study; Level of evidence, 3.
UNASSIGNED: This prospective proof-of-concept study included healthy individuals aged 16 to 40 years with no history of knee injury or surgery. Three adhesive surface markers were placed on predefined landmarks on the medial side of the knee. Three independent investigators examined anteromedial rotatory knee laxity with an anterior drawer test in different tibial rotations (neutral tibial rotation, 15° of external tibial rotation, and 15° of internal tibial rotation). The entire examination of each knee was recorded, and AMT including the side-to-side difference (SSD) was assessed using a freely available and validated image analysis software (PIVOT iPad application). Group comparisons were performed using a 1-way analysis of variance with Bonferroni-adjusted post hoc analysis. Intraclass correlation coefficients (ICCs) were calculated to assess inter- and intrarater reliability of AMT measurements. Equivalence of measurements was evaluated using the 2 one-sided t-test procedure.
UNASSIGNED: Anteromedial rotatory knee laxity was assessed in 30 knees of 15 participants (53% male) with a mean age of 26.2 ± 3.5 years. In all 3 raters, the highest AMT was observed in neutral tibial rotation (range of means, 2.2-3.0 mm), followed by external tibial rotation (range of means, 2.0-2.4 mm) and internal tibial rotation (range of means, 1.8-2.2 mm; P < .05). Intrarater reliability of AMT (ICC, 0.88-0.96) and SSD (ICC, 0.61-0.96) measurements was good to excellent and moderate to excellent, respectively. However, interrater reliability was poor to moderate for AMT (ICC, 0.44-0.73) and SSD (ICC, 0.12-0.69) measurements. Statistically significant equivalence of AMT and SSD measurements was observed between and within raters for almost all testing conditions.
UNASSIGNED: Anteromedial rotatory knee laxity could be quantified using a noninvasive image analysis software, with the highest AMT observed during neutral tibial rotation in uninjured individuals. Reliability and equivalence of measurements were good to excellent within raters and moderate between raters.

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.

OBJECTIVE: The purpose of this study was to retrospectively analyse the pattern of injury to the medial knee structures in anterior cruciate ligament (ACL) injured patients. It was hypothesised that anteromedial injuries would be more common than posteromedial lesions.
METHODS: One hundred and twenty subjects aged 18-25 years with a primary ACL injury were included. Patients were excluded if the time between injury and magnetic resonance imaging (MRI) was more than 28 days or if a knee dislocation or fracture was present. The MRIs were analysed with particular emphasis on injuries to the medial knee structures, menisci and bone bruise patterns. Injuries to the ligaments and anteromedial retinaculum (AMR) were graded according to severity, ranging from periligamentous oedema (grade I), partial fibre disruption of less or more than 50% (grade IIa or IIb) to complete tears (grade III).
RESULTS: AMR injury was seen in 87 subjects (72.5%) on the coronal plane and in 88 (73.3%) on the axial plane, with grade III lesions observed in 27 (22.5%) and 29 knees (24.2%). Injuries to the superficial medial collateral ligament (sMCL), deep MCL (dMCL) and posterior oblique ligament (POL) were detected in 60 patients (50%), 93 patients (77.5%) and 38 patients (31.6%). However, grade III injuries to the POL were observed in only seven knees (5.8%). Medial meniscus injuries were associated with lesions of the sMCL and AMR (p < 0.05), while lateral meniscus injuries were significantly more common in patients with dMCL rupture (p < 0.05).
CONCLUSIONS: Data from this study suggest that injuries to the AMR are much more common than posteromedial lesions in subjects with ACL injuries.
METHODS: Level IV.