Pediatric meniscus morphology varies with age: a cadaveric study.

PURPOSE: In adolescent patients, meniscal tear injury can occur either in isolation (e.g., discoid lateral meniscus tears) or in association with other traumatic injuries including tibial eminence fracture or ACL tear. Damage to meniscal integrity has been shown to increase contact pressure in articular cartilage, increasing risk of early onset osteoarthritis. In symptomatic patients failing conservative management, surgical intervention via meniscus repair or meniscus transplant is indicated. The purpose of this study was to evaluate the radial dimensions of pediatric menisci throughout development. The hypothesis was that the average radial meniscus dimensions will increase as specimen age increases, and mean medial and lateral region measurements will increase at a linear rate. METHODS: Seventy-eight skeletally immature knee cadaver specimens under age 12 years were included in this study. The meniscal specimens were photographed in the axial view with ruler in the plane of the tibial plateau and analyzed using computer-aided design (CAD) software (Autodesk Fusion 360). Measurements were taken from inner to outer meniscus rims at five 45 degree intervals using the clockface as a reference (12:00, 1:30, 3:00, 4:30, 6:00), and total area of meniscus and tibial plateau was recorded. Generalized linear models were used to evaluate the associations of radial width measurements with age, tibial coverage, and lateral vs. medial meniscus widths. RESULTS: All radial width measurements increased significantly with specimen age (p ≤ 0.002), and all lateral-medial meniscal widths increased (p < 0.001). The anterior zones of the meniscus were found to increase at the slowest rate compared to other regions. Tibial plateau coverage was found to not significantly vary with age. CONCLUSIONS: Meniscus radial width and lateral-medial meniscus width are related to age. The anterior width of the meniscus varied least with age. Improved anatomic understanding may help surgeons more effectively plan for meniscus repair, discoid resection/saucerization/repair, and also support appropriate selection of meniscus allograft for transplantation.

Self-reported cannabis use is not associated with greater opioid use in elective hand surgery patients.

BACKGROUND: The purpose of this study was to examine the influence of preoperative marijuana use on postoperative opioid use during the first three postoperative days (POD 1-3) after surgery, and on expectations of pain control, resiliency, and quality-of-life scores. METHODS: All patients presenting to a single institution undergoing elective hand or upper extremity outpatient surgery were asked to complete pre- and postoperative questionnaires. Preoperative questionnaires collected information on demographics, marijuana use, tobacco use, procedure type, self-assessed health, pain control expectations, and EuroQol-5D (EQ-5D) scores. At the first postoperative visit, patients self-reported opioid consumption from POD 1-3. Multivariate linear regression analysis was used to determine which patient characteristics were predictive of greater postoperative opioid consumption during POD 1-3. RESULTS: Self-reported marijuana users were younger, less healthy, and more likely to use tobacco compared to non-users. Marijuana users and non-users were comparable in their use of pain medication (including non-opioids), rates of chronic pain diagnoses, and self-reported pain tolerance. EQ-5D scores were lower in marijuana users than non-users (0.64 vs. 0.72). Marijuana users and non-users were prescribed comparable quantities of opioids during the first 14 days after surgery (176 ± 148 vs 115 ± 87). Multiple linear regression analysis revealed that lower preoperative EQ-5D scores, rather than marijuana use, were associated with increased opioid consumption during POD 1-3. CONCLUSIONS: Preoperative marijuana use was not independently associated with increased opioid use during POD 1-3 after elective hand and upper extremity surgery; instead, an association with lower preoperative EQ-5D scores was identified. LEVEL OF EVIDENCE: II, prospective cohort study.

Mind bomb 2 promotes cell migration and epithelial structure by regulating adhesion complexes and the actin cytoskeleton.

Cell migration is essential in animal development and co-opted during metastasis and inflammatory diseases. Some cells migrate collectively, which requires them to balance epithelial characteristics such as stable cell-cell adhesions with features of motility like rapid turnover of adhesions and dynamic cytoskeletal structures. How this is regulated is not entirely clear but important to understand. While investigating Drosophila oogenesis, we found that the putative E3 ubiquitin ligase, Mind bomb 2 (Mib2), is required to promote epithelial stability and the collective cell migration of border cells. Through biochemical analysis, we identified components of Mib2 complexes, which include E-cadherin and α- and ß-catenins, as well as actin regulators. We also found that three Mib2 interacting proteins, RhoGAP19D, Supervillin, and Myosin heavy chain-like, affect border cell migration. mib2 mutant main body follicle cells have drastically reduced E-cadherin-based adhesion complexes and diminished actin filaments. We conclude that Mib2 acts to stabilize E-cadherin-based adhesion complexes and promote a robust actin cytoskeletal network, which is important for maintenance of epithelial integrity. The interaction with cadherin adhesion complexes and other cytoskeletal regulators contribute to its role in collective cell migration. Since Mib2 is well conserved, it may have similar functional significance in other organisms.

Prevalence of Postoperative Micronutrient Deficiencies in Bariatric Surgery Patients Who Use Transdermal Patches for Supplementation: A Pilot Study.

Background Patients require vitamin and mineral supplementation after bariatric surgery to prevent the development of micronutrient deficiencies. Consuming oral supplements is challenging due to gastric volume restriction. A transdermal patch dosage form may provide adequate micronutrient supplementation without pill burden. The study aims to determine the percentage of patients who have two or more nutritional deficiencies one year after surgery and to determine serum nutrient concentrations and gastrointestinal symptoms over time. Methods Patients who planned to undergo bariatric surgery and preferred transdermal patches versus oral supplements were recruited during preoperative office visits. Enrolled patients were instructed to use a transdermal multivitamin patch as per the manufacturer's instructions. Serum nutrient concentrations and Gastrointestinal Symptom Response Scale scores were determined at baseline and three months, six months, and one year after surgery. Results Ninety-two participants completed the study protocol. Twenty-five participants had a full panel of study labs one year after surgery. Among these patients, 19% had two or more micronutrient deficiencies. Vitamin D was the most common deficiency followed by vitamin B6; however, median serum concentrations of both nutrients increased over time. Vitamin B1, folate, and zinc deficiencies were also observed. There were no changes in gastrointestinal symptoms. Conclusions Additional studies, including randomized controlled trials, are required to determine if the PatchMD Multivitamin Plus patch (Pilot Rd. STE. B, Las Vegas) can provide adequate supplementation of vitamins and minerals. The patch was not associated with changes in gastrointestinal symptoms.

Paediatric reference anatomy for ACL reconstruction and secondary anterolateral ligament or lateral extra-articular tenodesis procedures.

OBJECTIVES: For iliotibial band (ITB) lateral extra-articular tenodesis or anterolateral ligamentous/capsular reconstruction with anterior cruciate ligament reconstruction, a clear understanding of the referenced anterolateral knee anatomy is critical-especially given the risk of injury to the physis or key anterolateral structures in the paediatric population, which is at high-risk for primary and secondary anterior cruciate ligament injury. The purpose of this study was to quantitatively assess the anatomy of the knee physes, paediatric lateral collateral ligament (LCL) origin, popliteus origin and ITB tibial insertion. METHODS: Nine paediatric cadaveric knee specimens with average age 4.2 years (range 2 months-10 years) underwent dissection to identify the LCL's and popliteus' femoral origins and the ITB's tibial insertion. Metallic marking pins demarcated precise anatomic attachment sites, and subsequent computerised tomography scans enabled quantified measurements among them. RESULTS: LCL & Popliteus: On the femur, the popliteus origin lay consistently deep to the LCL and inserted both distally and anteriorly to the LCL, a mean distance of 4.6 mm (range 1.9-7.6; standard deviation 2.0). From the joint line, the LCL lay a mean distance of 12.5 mm proximally while the popliteus measured a mean of 8.2 mm. Both were consistently distal to the physis. The LCL was a mean distance of 4.4 mm (range 1.0-9.5) and the popliteus was a mean distance of 8.2 (range 1.7-12.5) from the physis. ITB insertion: The ITB insertion at Gerdy's tubercle had an average footprint measuring 28.2 mm2 (range 10.3-58.4) and the ITB centre lay proximal to the physis in 6 specimens (mean age 4.2 years, median 2.5 years) and distal in 3 specimens (mean age 1.5 years, median 4 months). Mean distance from the footprint centre to the physis was 1.6 mm proximal (range 7.1 proximal - 2.2 distal). CONCLUSION: This study describes relative and quantitative positions of the femoral LCL and popliteus origins and tibial ITB attachment and their respective physeal relationships. Knowledge of paediatric anterolateral knee anatomy will help guide essential future research and procedures providing extra-articular anterolateral rotatory stabilisation and may help reduce iatrogenic physeal injury risk. LEVEL OF EVIDENCE: N/A (descriptive anatomic study).

The Axillary Nerve Danger Zone in Percutaneous Fixation in the Pediatric Shoulder: The "1-Mountain-3-Valleys" Principle.

BACKGROUND: Adult literature cites an axillary nerve danger zone of 5 to 7 cm distal to the acromion tip for open or percutaneous shoulder surgery, but that may not be valid for younger patients. This study sought to quantify the course of the axillary nerve in adolescent patients with reference to easily identifiable intraoperative anatomic and radiographic parameters. METHODS: A single-institution hospital database was reviewed for shoulder magnetic resonance images (MRIs) in patients 10 to 17 years old. One hundred and one MRIs from patients with a mean age of 15.6 ± 1.2 years (range, 10 to 17 years) were included. Axillary nerve branches were identified in the coronal plane as they passed lateral to the proximal humerus and were measured in relation to identifiable intraoperative surface and radiographic landmarks, including the acromion tip, apex of the humeral head, lateral physis, and central apex of the physis. The physeal apex height (i.e., 1 "mountain") was defined as the vertical distance between the most lateral point of the humeral physis (LPHP) and the central intraosseous apex of the physis. RESULTS: Axillary nerve branches were found in all specimens, adjacent to the lateral cortex of the proximal humerus. A mean of 3.7 branches (range, 2 to 6) were found. The mean distance from the most proximal branch (BR1) to the most distal branch (BR2) was 11.7 mm. The pediatric danger zone for the axillary nerve branches ranged from 6.6 mm proximal to 33.1 mm distal to the LPHP. The danger zone in relation to percent of physeal apex height included from 62% proximal to 242% distal to the LPHP. CONCLUSIONS: All branches were found distal to the apex of the physis (1 "mountain" height proximal to the LPHP). Distal to the LPHP, no branches were found beyond a distance of 3 times the physeal apex height (3 "valleys"). In children and adolescents, percutaneous fixation of the proximal humerus should be performed with cortical penetration outside of this range. These parameters serve as readily identifiable intraoperative radiographic landmarks to minimize iatrogenic nerve injury. CLINICAL RELEVANCE: This study provides valuable landmarks for percutaneous approaches to the proximal humerus. The surgical approach for the placement of percutaneous implants should be adjusted accordingly (i.e., performed at least 1 mountain proximal or 3 valleys distal to the LPHP) in order to prevent iatrogenic injury to the axillary nerve.

A Quality Improvement Project to Reduce Combination Acetaminophen-opioid Prescriptions to Pediatric Orthopedic Patients.

BACKGROUND: Acetaminophen-opioid analgesics are among the most commonly prescribed pain medications in pediatric orthopedic patients. However, these combined opioid analgesics do not allow for individual medication titration, which can increase the risk of opioid misuse and hepatoxicity from acetaminophen. The primary aim of this quality improvement project was to alter the prescribing habits of pediatric orthopedic providers at our institution from postoperative acetaminophen-opioid analgesics to independent acetaminophen and opioids. METHODS: The study took place in a level 1 trauma center at a children's hospital. A multidisciplinary team of health professionals utilized lean methodology to develop a project plan. Guided by a key driver diagram, we removed acetaminophen-oxycodone products from hospital formulary, implemented a revised inpatient and outpatient electronic order set, and conducted multiple education efforts. Outcomes included inpatient and outpatient percent combined acetaminophen-opioid orders by surgical providers over 27 months. RESULTS: Before the intervention, inpatient acetaminophen-opioid products accounted for an average of 46% of all opioid prescriptions for orthopedic patients. After the intervention and multiple educational efforts, we reported a reduction in the acetaminophen-opioid products to 2.9%. For outpatient prescriptions, combined analgesics accounted for 88% before the intervention, and we reported a reduction to 15% after the intervention. CONCLUSIONS: By removing acetaminophen-oxycodone products from hospital formulary, educating the medical staff, and employing revised electronic order sets, the prescribing practice of pediatric orthopedic surgeons changed from the routine use of acetaminophen-opioid analgesics to independent medications.

Pharmacotherapeutic considerations and options for the management of osteoarthritis in women.

Introduction: Osteoarthritis is a chronic disease that leads to the destruction of articular cartilage and joints. As the most common joint disorder, osteoarthritis poses a great burden to the healthcare system. Most importantly, osteoarthritis is a heterogeneous disease characterized by a wide range of clinical features, phenotypes, and treatments. The burden of osteoarthritis is not equally distributed between men and women. Women have an increased risk of developing osteoarthritis, with worse symptoms, and poorer outcomes.Areas covered: In this paper, the authors discuss pathophysiological considerations such as the wide spectrum of OA phenotypes. Women share many OA phenotypes with men including genetics, age, and trauma. Specific phenotypes from metabolic, anatomical, and hormonal influences vary greatly between the two sexes. This paper discusses the various current pharmacological treatment options for osteoarthritis including NSAIDs, Acetaminophen, Opioids, Duloxetine, SYSADOAs, monoclonal antibodies, intra-articular injections and hormonal therapy.Expert opinion: Further investigations of the pathophysiology of osteoarthritis are necessary to improve treatment options specific to women. As our understanding of the complex biology of osteoarthritis and the information surrounding it improves, newer and more effective treatments may decrease the suffering of osteoarthritis in a more efficient and less costly way.

Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis.

Over the past three-decades, Janus kinase (Jak) and signal transducer and activator of transcription (STAT) signaling has emerged as a paradigm to understand the involvement of signal transduction in development and disease pathology. At the molecular level, cytokines and interleukins steer Jak/STAT signaling to transcriptional regulation of target genes, which are involved in cell differentiation, migration, and proliferation. Jak/STAT signaling is involved in various types of blood cell disorders and cancers in humans, and its activation is associated with carcinomas that are more invasive or likely to become metastatic. Despite immense information regarding Jak/STAT regulation, the signaling network has numerous missing links, which is slowing the progress towards developing drug therapies. In mammals, many components act in this cascade, with substantial cross-talk with other signaling pathways. In Drosophila, there are fewer pathway components, which has enabled significant discoveries regarding well-conserved regulatory mechanisms. Work across species illustrates the relevance of these regulators in humans. In this review, we showcase fundamental Jak/STAT regulation mechanisms in blood cells, stem cells, and cell motility. We examine the functional relevance of key conserved regulators from Drosophila to human cancer stem cells and metastasis. Finally, we spotlight less characterized regulators of Drosophila Jak/STAT signaling, which stand as promising candidates to be investigated in cancer biology. These comparisons illustrate the value of using Drosophila as a model for uncovering the roles of Jak/STAT signaling and the molecular means by which the pathway is controlled.