Casz1 is required for cardiomyocyte G1-to-S phase progression during mammalian cardiac development

Organ growth occurs through the integration of external growth signals during the G1 phase of the cell cycle to initiate DNA replication. Although numerous growth factor signals have been shown to be required for the proliferation of cardiomyocytes, genetic studies have only identified a very limited number of transcription factors that act to regulate the entry of cardiomyocytes into S phase. Here, we report that the cardiac para-zinc-finger protein CASZ1 is expressed in murine cardiomyocytes. Genetic fate mapping with an inducible Casz1 allele demonstrates that CASZ1-expressing cells give rise to cardiomyocytes in the first and second heart fields. We show through the generation of a cardiac conditional null mutation that Casz1 is essential for the proliferation of cardiomyocytes in both heart fields and that loss of Casz1 leads to a decrease in cardiomyocyte cell number. We further report that the loss of Casz1 leads to a prolonged or arrested S phase, a decrease in DNA synthesis, an increase in phospho-RB and a concomitant decrease in the cardiac mitotic index. Taken together, these studies establish a role for CASZ1 in mammalian cardiomyocyte cell cycle progression in both the first and second heart fields

In-office arthroscopy for the evaluation of chronic knee pain: A case report

This is a case report detailing the use of in-office needle arthroscopy (mi-eye 2™) in a patient with chronic knee pain and inconclusive magnetic resonance imaging findings. The patient is a 40-year-old male who presented to our clinic after an extended history of right knee pain along the medial aspect with previous failed treatments. Magnetic resonance imaging without contrast had demonstrated full-thickness chondral fissuring of the lateral patellar facet, mild abnormal signals of the proximal patellar tendon and Hoffa’s fat pad, and intact anterior cruciate ligament and posterior cruciate ligament. The patient was previously treated with an ultrasound-guided injection of 2 cm 3 of 1% lidocaine without epinephrine and 1 cm 3 of Kenalog-40 and scheduled for follow-up. At follow-up, clinical examination showed antalgic gait, minimal tenderness along medial joint line, medial pain in deep flexion, and no pain when in varus or valgus. Due to continued discomfort with a negative magnetic resonance imaging, in-office diagnostic arthroscopy was performed using mi-eye 2 revealing a tear of the mid-body of the medial meniscus. The patient subsequently underwent arthroscopic repair and is recovering well with complete resolution of medial joint pain. This report highlights the clinical utility of in-office diagnostic arthroscopy in the management of patients with persistent knee pain and negative or equivocal findings on magnetic resonance imaging

The Benefits of an In-Office Arthroscopy in the Diagnosis of Unresolved Knee Pain

We report a patient who developed persistent knee pain with mechanical symptoms after an uncomplicated patellofemoral arthroplasty. The etiology of his knee pain remained inconclusive following magnetic resonance imaging due to metallic artifact image distortion. With the use of an in-office needle arthroscopy, an immediate and definitive diagnosis was obtained, preventing an unnecessary surgery for a diagnostic arthroscopy. We discovered a lateral meniscus tear, an anterior cruciate ligament tear, and a medial femoral condyle chondral defect for which the patient underwent arthroscopic partial meniscectomy, ligament reconstruction, and osteochondral allograft transplantation, with resolution of his knee pain

Surgical Treatment of Insufficiency Fractures of the Knee

Bone marrow lesions (BMLs) in the knee represent focal edema caused by subchondral bone attrition and microfractures to the trabecular bone. These lesions are poor prognostic indicators for several orthopaedic procedures but also have been associated with the progression of osteoarthritis. Current research is aimed at treating BMLs with the intent to improve the overall structural integrity of the subchondral bone and delay the need for arthroplasty. The injection of calcium phosphate bone substitute has been proposed to treat BMLs because animal models have shown its potential to stimulate bone repair. This technical note describes the key steps involved in performing percutaneous fixation of BMLs with a hard-setting bone substitute, as well as associated pearls and pitfalls. Although continued research with prospective comparative cohorts and long-term follow-up is needed to determine the efficacy of this procedure, this intervention holds promise in delaying the need for total knee replacement in the arthritic patient with a focal lesion

Chondrotoxicity of Local Anesthetics: Liposomal Bupivacaine Is Less Chondrotoxic than Standard Bupivacaine

Objective. The purpose of this study is to determine whether (1) liposomal bupivacaine is chondrotoxic; (2) the chondrotoxicity of liposomal bupivacaine differs from standard bupivacaine; and (3) chondrotoxic effects are time dependent. Materials and Methods. We obtained 72 10 mm articular cartilage plugs from 12 fresh bovine distal femoral knee joints and exposed them to either saline, 0.5% bupivacaine, or liposomal bupivacaine for either 30 or 90 minutes. Twenty-four hours after treatment, chondrocyte viability was measured with the use of a fluorescent live/dead assay. An ANOVA test of variance was performed followed by a Holm–Sidak test to make pairwise comparisons across conditions. Student’s t-test was used to compare means. Results. Percent viability of cells exposed to liposomal bupivacaine for 30 minutes was less versus saline control (53.9% ± 21.5% vs. 73.7 ± 18.4%, p=0.035), and this remained significant at 90 minutes (49.1% ± 20.3% vs. 67.2% ± 25.6%, p<0.001). Liposomal bupivacaine had less chondrotoxic effects when compared with bupivacaine after 90 minutes, with greater viability (49.1% ± 20.3% vs. 21.4% ± 14.0%, p=0.003). Chondrotoxicity was found to be time dependent within the bupivacaine group (percent viability at 30 min: 45.5 ± 18.2%, 90 min: 21.4 ± 14.0%, p=0.001); however, liposomal bupivacaine did not demonstrate a significant time-dependent chondrotoxic relationship (p=0.583). Conclusions. Bupivacaine and liposomal bupivacaine are both toxic to chondrocytes. Liposomal bupivacaine is less chondrotoxic than standard bupivacaine and does not demonstrate a time-dependent toxicity

A 15-Minute Incremental Increase in Operative Duration Is Associated With an Additional Risk of Complications Within 30 Days After Arthroscopic Rotator Cuff Repair

Background: Operative time is a risk factor for short-term complications after orthopaedic procedures; however, it has yet to be investigated as an independent risk factor for postoperative complications after arthroscopic rotator cuff repair. Purpose: To determine whether operative time is an independent risk factor for complications, readmissions, and extended hospital stays within 30 days after arthroscopic rotator cuff repair. Study Design: Descriptive epidemiology study. Methods: The American College of Surgeons National Surgical Quality Improvement Program was queried for all hospital-based inpatient and outpatient arthroscopic rotator cuff repairs (Current Procedural Terminology code 29827) from 2005 to 2016. Concomitant procedures such as subacromial decompression, biceps tenodesis, superior labrum anterior and posterior (SLAP) repair, labral repair, and distal clavicle excision were also included, whereas patients undergoing arthroplasty were excluded from the study. Operative time was correlated with patient demographics, comorbidities, and concomitant procedures. All adverse events were correlated with operative time, while controlling for the above preoperative variables, using multivariate Poisson regression with a robust error variance. Results: A total of 27,524 procedures met inclusion and exclusion criteria. The mean age of patients was 58.4 +/- 10.9 years, the mean operative time was 86.9 +/- 37.4 minutes, and the mean body mass index was 30.4 +/- 7.0 kg/m(2). Concomitant biceps tenodesis, glenohumeral debridement, SLAP repair, labral repair, and distal clavicle excision significantly increased operative time (P .05). The overall rate of adverse events was 0.88%. After adjusting for demographic and procedural characteristics, a 15-minute increase in operative duration was associated with an increased risk of anemia requiring transfusion (relative risk [RR], 1.27 [95% CI, 1.14-1.42]; P \u3c .001), venous thromboembolism (RR, 1.17 [95% CI, 1.02-1.35]; P = .029), surgical site infection (RR, 1.13 [95% CI, 1.03-1.24]; P = .011), and extended length of hospital stay (RR, 1.07 [95% CI, 1.00-1.14]; P = .036). Conclusion: Although the rate of short-term complications after arthroscopic rotator cuff repair is low, incremental increases in operative time are associated with an increased risk of adverse events such as surgical site infection, pulmonary embolism, transfusion, and extended length of hospital stay. Efforts should be made to maximize surgical efficiency in the operating room through optimal coordination of the staff or increased preoperative planning