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Coactivation of NF-κB and Notch signaling is sufficient to induce B cell transformation and enables B-myeloid conversion

Xiu, Yan; Dong, Qianze; Fu, Lin; Bossler, Aaron; Tang, Xiaobing; Boyce, Brendan; Borcherding, Nicholas; Leidinger, Mariah; Sardina, José Luis; Xue, Hai-Hui; Li, Qingchang; Feldman, Andrew; Aifantis, Iannis; Boccalatte, Francesco; Wang, Lili; Jin, Meiling; Khoury, Joseph; Wang, Wei; Hu, Shimin; Yuan, Youzhong; Wang, Endi; Yuan, Ji; Janz, Siegfried; Colgan, John; Habelhah, Hasem; Waldschmidt, Thomas; Müschen, Markus; Bagg, Adam; Darbro, Benjamin; Zhao, Chen
NF-kB and Notch signaling can be simultaneously activated in a variety of B cell lymphomas. Patients with B cell lymphoma occasionally develop clonally-related myeloid tumors with poor prognosis. Whether concurrent activation of both pathways is sufficient to induce B cell transformation and the signaling initiates B-myeloid conversion in a pathological context are largely unknown. Here, we provide genetic evidence that concurrent activation of NF-kB and Notch signaling in committed B cells is sufficient to induce B cell lymphomatous transformation and primes common progenitor cells to convert to myeloid lineage through dedifferentiation, not transdifferentiation. Intriguingly, the converted myeloid cells can further transform, albeitat low frequency, to myeloid leukemia. Mechanistically, coactivation of NF-kB and Notch signaling endows committed B cells with the ability to self-renew. Downregulation of BACH2, a lymphoma and myeloid gene suppressor, but not upregulation of CEBPa and/or downregulation of B cell transcription factors, is one of the early events for both B cell transformation and myeloid conversion. Interestingly, a DNA hypomethylating drug not only effectively eliminated the converted myeloid leukemia cells, but also restored the expression of GFP, which was lost in converted myeloid leukemia cells. Collectively, our results suggest that targeting NF-kB and Notch signaling will not only improve lymphoma treatment, but also prevent the lymphoma-to-myeloid tumor conversion. Importantly, DNA hypomethylating drugs might efficiently treat these converted myeloid neoplasms.
PMID: 31697816
ISSN: 1528-0020
CID: 4179492

Clinical Outcomes of Open Subpectoral Biceps Tenodesis with Cortical Button Fixation

Baron, Samuel L; Shamah, Steven; McGee, Alan W; Alaia, Michael J; Feldman, Andrew J; Jazrawi, Laith M
BACKGROUND:Open subpectoral biceps tenodesis (OSBT) with cortical button fixation can deliver acceptable results for long head of the biceps (LHB) pathology with the benefit of smaller bone tunnel diameter and a potential reduced risk of postoperative humeral shaft fracture. However, functional outcomes and complications of a button-only technique with a small diameter tunnel in the subpectoral region have not been studied sufficiently. PURPOSE/OBJECTIVE:We sought to determine whether OSBT with cortical button fixation results in significant functional improvements from preoperative to final follow-up. The secondary purpose was to determine whether there is a lower risk of major postoperative complications. METHODS:A retrospective review of patients who underwent OSBT with cortical button fixation at one institution was conducted with objective measurements and clinical outcomes collected with a minimum of 2 years of follow-up. Surgical data was collected for analysis. Objective measures obtained at follow-up included physical exam, strength testing using a handheld dynamometer, and Long-Head of the Biceps score. Clinical outcomes were measured using the following validated questionnaires preoperatively and postoperatively: American Shoulder and Elbow Surgeons score (ASES), Disabilities of the Arm, Shoulder and Hand score (DASH), and Oxford Shoulder Score (OSS). RESULTS:Sixty-one patients with mean age of 53.1 ± 10.1 years at the time of surgery were enrolled in the study. Mean follow-up time was 42.4 ± 16.9 months (range: 24 to 64 months). The postoperative LHB score was 95.5 ± 6.1 (range: 77 to 100). All functional outcome measures (ASES, DASH, and OSS) demonstrated statistically significant improvements at final follow-up (p < 0.05 for each). At total of 92.5% of patients stated they would have the procedure again if necessary. Mean elbow flexion strength on the operative side measured 98.7% ± 15.9% (range: 74.1% to 142.3%) of the contralateral arm. The mean LHB tendon diameter was 5.7 ± 0.8 mm and mean tunnel diameter was 5.9 ± 0.7 mm. There were no cases of intraoperative or postoperative fracture, infection, or Popeye deformity noted during the follow-up period. CONCLUSION/CONCLUSIONS:Subpectoral biceps tenodesis with cortical button fixation is a safe and effective surgical treatment option to relieve pain and restore function.
PMID: 31785136
ISSN: 2328-5273
CID: 4238102

Clinical Outcomes after Mini-Open Excision of Popliteal Cysts

Snir, Nimrod; Wolfson, Theodore; Pham, Hien; Dai, Amos; Sherman, Orrin; Feldman, Andrew; Jazrawi, Laith
PURPOSE/OBJECTIVE:The purpose of the study was to investigate clinical outcomes following a mini-open posterior technique. METHODS:Patients who received mini-open popliteal cyst excisions between April 1999 and April 2010 were identified. Charts were retrospectively reviewed for postoperative complications, cyst recurrence, previous aspiration, re-operation, intraoperative findings, cyst size, comorbidities, and co-surgeries. Visual Analogue Pain Scale and Rauschning's symptomatic knee criteria were collected prospectively to assess functional outcomes. RESULTS:Twenty-two legs in 21 patients were included in the study [males: 12 (57%); females: 9 (43%); age: 48.23 ± 11.74 years; BMI: 26.7 ± 4.54 kg/m2; follow-up: 4.55 ± 3.01 years]. Average cyst size was 4.16 ± 1.64 cm and were all located in the posteromedial aspect of the leg. All 22 cases had associated intra-articular pathology based on MRI, physical examination, and arthroscopy. Complications after cyst excision included: paresthesia in the distribution of the saphenous nerve (3/22, 14%), keloid formation (1/22, 4%), joint effusion requiring aspiration (1/22, 4%), and one recurrence requiring cystectomy 10 years later (4%). All incidences of paresthesia resolved. Mean visual analog pain score decreased by 6 points (p < 0.001) and Rauschning and Lindgren score decreased by two categories, from a 2.6 (category 2-3) preoperatively to 0.6 (category 0-1) postoperatively (p < 0.001). CONCLUSION/CONCLUSIONS:Mini-open popliteal cyst excision is a safe and effective technique for refractory popliteal cysts in patients who desire a decrease in pain, an increase range of motion, and improved function in knee flexion and extension. Further studies are needed to evaluate the clinical outcomes of patients over a longer duration as our one patient with a 10-year follow-up required a repeat procedure.
PMID: 31487479
ISSN: 2328-5273
CID: 4153392

Regional histologic differences in the long head of the biceps tendon following subpectoral biceps tenodesis in patients with rotator cuff tears and SLAP lesions

Glait, Sergio A; Mahure, Siddharth; Loomis, Cynthia A; Cammer, Michael; Pham, Hien; Feldman, Andrew; Jazrawi, Laith M; Strauss, Eric J
PURPOSE/OBJECTIVE:The purpose of this study was to quantify the regional histology of the long head of the biceps tendon (LHBT) and compare the histopathology present to clinical findings in patients with rotator cuff tears and SLAP lesions. METHODS:Prospectively enrolled patients undergoing an open subpectoral LHBT tenodesis in the setting of a rotator cuff (RTC) tear or SLAP lesion. Perioperative data were collected and the excised LHBT was analyzed by a fellowship trained pathologist. Tendons were sectioned into proximal (biceps anchor), middle (bicipital groove), and distal (myotendinous junction) portions. Sections were stained with Movat's pentachrome stain and digitized for analysis. Comparisons were made between the histologic findings present in the setting of a rotator cuff tear with those seen in the setting of a SLAP tear. RESULTS:39 tendons were analyzed: 20 from patients with SLAP lesions (mean age of 44.7 years, range 23-60 years) and 19 from patients with rotator cuff tears (mean age of 58.7 years, range 43-71). Patients with the most pathologic tendons in the bicipital groove were significantly older (59.4 vs. 50.4 years; p < 0.05), reported higher pre-operative VAS scores (6.6 vs. 5.0; p < 0.02), and demonstrated lower pre-operative ASES scores (41.6 vs. 50.7; p < 0.05). The RTC group showed significantly more mucinous degeneration at both the proximal (p < 0.03) and the middle (p < 0.01) tendon portions compared to the SLAP group. In both groups, the portions of proximal tendon showed significantly (p < 0.05) more mucinous degeneration than distal portions. CONCLUSION/CONCLUSIONS:Regional histologic differences exist in the LHBT. Rotator cuff patients showed the most degenerated tendon in the bicipital groove and these patients tended to be older and have higher VAS and lower ASES scores. Surgeons should consider performing a subpectoral biceps tenodesis as the bicipital groove portion of the tendon may be very degenerated, especially in patients with rotator cuff disease. Additional research is warranted to distinguish whether treating the biceps differently in distinct geographic regions affects patient outcomes. LEVEL OF EVIDENCE/METHODS:II.
PMID: 29362860
ISSN: 1433-7347
CID: 2929272

Shoulder Range of Motion and Strength in Professional Ice Hockey Players

Cohn, Randy M; Strauss, Eric J; Jazrawi, Laith M; Feldman, Andrew J
Ice hockey is a fast paced sport with unique injury potential. There are no studies in the literature that examine the shoulder strength and range of motion in this population. Players on a single professional ice hockey team underwent a comprehensive examination of shoulder motion and strength. Shoulder motion and strength between right and left extremities were compared within athletes. Comparisons were made between right and left handed players, players that shoot right versus left handed, and by position. Within individual athletes, there was no difference in motion or strength between right and left shoulders. There was no difference in motion or strength between the dominant and non-dominant shoulder and players that shoot right versus left handed. Defensemen had a statistically significant increase in external rotation with the arm at the side for the left shoulder (66 degrees versus 55 degrees , p = 0.02) and a trend towards increased external rotation with the arm at the side for the right shoulder (65 degrees versus 56 degrees , p = 0.07). In professional ice hockey players, there is no difference in shoulder motion and strength between the right and left upper extremity. Ice hockey defensemen may have more external rotation with the arm at the side than forward.
PMID: 26516995
ISSN: 2328-5273
CID: 1874012

Popliteal cyst excision using open posterior approach after arthroscopic partial medial meniscectomy

Snir, Nimrod; Hamula, Mathew; Wolfson, Theodore; Sherman, Orrin; Feldman, Andrew
Popliteal cysts are known to be associated with intra-articular pathology, which must be addressed to prevent cyst recurrence. Indications for popliteal cyst excision include cases in which the popliteal cyst does not respond to conservative treatment or arthroscopic intervention or cases in which an underlying cause cannot be found. Several techniques have been described to excise these cysts. Traditionally, open techniques have been associated with cyst recurrence. More recently, arthroscopic cystectomy has been described. However, the risk of recurrence persists because arthroscopy may not afford complete surgical excision. This technical note presents an open posterior technique for popliteal cyst excision that allows for better visualization and complete removal of the cyst while minimizing the risk of neurovascular complications and soft-tissue damage. It is a safe, effective, and straightforward method to achieve symptomatic relief for refractory popliteal cysts.
PMID: 24266002
ISSN: 2212-6287
CID: 778002

The mechanical effects of suture anchor insertion angle for rotator cuff repair

Liporace, Frank A; Bono, Christopher M; Caruso, Steven A; Weiner, Bradley; Penny, Keith; Feldman, Andrew J; Grossman, Mark G; Haher, Thomas R
Twelve matched pairs of humerii were instrumented with suture anchor at 90 degrees, 75 degrees, 45 degrees, and 30 degrees relative to the cortical border at the junction of the greater tuberosity and articular surface. Two fixtures were inserted into each specimen at different angles and loaded to failure. Suture anchors failed at an average of 171, 219, 169, and 192 N with 90 degrees, 75 degrees, 45 degrees, and 30 degrees insertion angles, respectively. No statistical difference was detected between groups (P=.08). Although previous authors have prescribed angles < or =45 degrees to improve pull-out strength, the current in vitro data does not support these recommendations
PMID: 12002210
ISSN: 0147-7447
CID: 109154