The Internal Joint Stabilizer of the Elbow: A Systematic Review of the Clinical and Biomechanical Evidence.

Purpose: The goal of surgical management for unstable elbow injuries is the restoration of joint concentricity and stability. After internal fixation, concerns may exist regarding instability or durability of the fixation construct. Historically, these scenarios were treated with options such as transarticular pinning or external fixation. Recently, an internal joint stabilizer (IJS) that allows postoperative mobilization was introduced. Our objective was to systematically review the literature to aggregate the clinical and biomechanical evidence for the IJS of the elbow. Methods: A systematic review of the PubMed and Google Scholar databases was performed, following the PRISMA guidelines. The search results were narrowed from 2015 through 2023 to coincide with the inception of the device being reviewed. Results: A total of nine retrospective reports on the IJS (N = 171) cases at a mean follow-up of 10.8 months were included. The pooled rate of implant failure was 4.4%, and recurrent instability was 4.1%. Additionally, the we included seven case reports and two biomechanical reports. Conclusions: The aggregate literature describes satisfactory clinical outcomes with low rates of recurrent instability and device failure for the IJS of the elbow. The limited biomechanical investigations conclude efficacy for stability profiles. Clinical relevance: Across a spectrum of unstable elbow cases, the IJS prevented recurrent instability during the early postoperative period. Notably, the device requires an additional procedure for removal, and the long-term impact of the retained devices is currently unclear.

Scaphoid fracture and nonunion: new directions.

The scaphoid is the largest of the carpal bones, articulating with both proximal and distal carpal rows. If scaphoid fractures are not appropriately diagnosed and treated, there is a risk of nonunion, osteonecrosis and degenerative arthritis. Operative management of the scaphoid fracture is primarily determined by the fracture location and amount of displacement. There is increased momentum for dual screw fixation constructs, intended to provide greater stability and reduce the risk of nonunion. Our current practice is to utilize two screws without graft as a first-line treatment for scaphoid nonunion with or without humpback deformity and cyst formation. This review will discuss the management of acute scaphoid fractures and the treatment of nonunion.

Novel Descriptions of the Radial Osteotomy in Kienböck's Disease: A Systematic Review.

Purpose: Kienböck's disease consists of intrinsic and extrinsic characteristics that coalesce into a pathology with multifactorial etiology. Mechanical, morphological, and vascular factors have been identified as contributory. Radial osteotomy is one of the most commonly used surgical treatment for late-stage Kienböck's disease. Despite its frequent use and reported value, the specifics of radial osteotomy have not been described in aggregate. Our objective was to review the recent literature for descriptions of the radial osteotomy techniques used for treatment of Kienböck's disease. Methods: The inclusion criteria for the systematic review were as follows: (1) patients aged >18 years, (2) a publication date no older than 2012, and (3) a complete description of the distal radius osteotomy technique, including verbiage that specified numeric dimensions of bony resection or verbiage that detailed a goal in terms of a radiographic parameter that would guide the bony resection. Results: The studies were grouped according to the stated description of radial osteotomy. This process yielded the following three main groups: (1) studies that used radial shortening, (2) studies that used lateral closing wedge osteotomy or combined lateral closing wedge with radial shortening, and (3) novel osteotomy descriptions. Conclusions: The Kienböck's disease literature predominantly describes an osteotomy to shorten the radius by 2-3 mm. In some studies, the degree of radial shortening corresponded to the value necessary to achieve near-neutral ulnar variance. The common goal in using lateral closing wedge osteotomy was to achieve a radial inclination of 5° to 15°. Unique wedge resections, some with multiplanar corrections, have been recently described with each purporting specific advantages. Clinical relevance: Our findings support the premise of mechanical and biologic efficacy for radial osteotomy, with satisfactory results being reported across a wide spectrum of osteotomy techniques.

Immunoprecipitation and Western Blot Analysis of AP-1 Clathrin-Coated Vesicles.

The function and integrity of epithelial cells depends on the polarized localization of transmembrane proteins at either apical or basolateral plasma membrane domains. To facilitate sorting to the basolateral domain, columnar epithelial cells express the tissue-specific AP-1B complex in addition to the ubiquitously expressed AP-1A. Both AP-1A and AP-1B are heterotetrameric clathrin adaptor protein complexes that are closely related. Here we describe a biochemical method to separate AP-1B from AP-1A clathrin-coated vesicles by immunoprecipitation from clathrin-coated vesicle pellets that were obtained by ultracentrifugation and analyzed by SDS-PAGE and western blot using fluorescently labeled secondary antibodies.

Acute on Chronic Distal Radius Fracture: A Case Series and Technique Description.

Purpose: Distal radius fractures are the most common fractures in adults. Because of the prevalence of these injuries, patients may present with a repeat distal radius fracture on the same wrist through the site of a malunion. We clinically refer to this as an acute on chronic distal radius fracture. In this setting, the restoration of acceptable alignment can be challenging. There is little guidance in the literature for the management of these fractures. We report our experience with acute on chronic distal radius fractures. The secondary fracture plane was used to correct the prior deformity, and the construct was fixated with a fixed angle volar locking plate. Methods: Records of patients with malunion of the distal radius who experienced an acute fracture of the ipsilateral distal radius were reviewed. Inclusion required treatment with open reduction internal fixation using a distal fragment first technique and a volar locking plate through the extended flexor carpi radialis approach. Clinical outcomes and complications were collected. Results: Across 13 patients, the mean follow-up term was 13 months (range, 6-40 months). Radiographic union was noted in all patients. The mean visual analog scale score for pain was 1.8, and the mean Quick Disabilities of the Arm, Shoulder, and Hand score was 21.9. There were no recorded complications. Conclusion: Our results and described technique provide reproducible guidance for the management of acute on chronic distal radius fractures. These cases can be managed using the secondary fracture plane, a distal fragment first technique, and a volar locking plate to correct the preexisting deformity. Type of study/level of evidence: Therapeutic IV.

Chronic Posterior Tibiofemoral Dislocation of a Cruciate Retaining Total Knee Arthroplasty in the Setting of Wernicke-Korsakoff Syndrome: A Case Report.

Introduction: Knee dislocations are an uncommon complication following total knee arthroplasty (TKA). There are many causes of TKA dislocation; however, Wernicke-Korsakoff syndrome is one uncommon neurologic condition that increases the risk of TKA dislocation. Case Report: A 71-year-old male with presented to a local community hospital with knee pain due to advanced osteoarthritis of the knee and subsequently underwent an uncomplicated TKA with a cruciate retaining prosthesis. He eventually returned to the hospital due to infection, medical instability, chronic knee instability, and posterior tibiofemoral dislocation. A revision process was required. Throughout the course of management, the patient had altered mental status and was admitted to the intensive care unit. The first procedure involved removing the cruciate retaining prosthesis and replacing it with a static cement antibiotic spacer. This prosthesis was eventually dislocated through the tibia and a second procedure requiring the placement of an intercalary fusion was needed. The patient has not followed up after the hospital admission. Conclusion: Wernicke-Korsakoff Syndrome is an uncommon condition that affects alcoholics and complicates treatment with joint replacement surgery. Patients with Wernicke-Korsakoff syndrome provide a unique set of challenges that may require multiple surgeries and varying prostheses. Chronic posterior tibiofemoral dislocation is one specific complication that may affect the management of these patients. As orthopedic surgeons, it is important to consider alcohol use disorder and Wernicke-Korsakoff Syndrome when treating patients with total joint replacement.

Novel function for AP-1B during cell migration.

The epithelial cell-specific clathrin adaptor protein (AP)-1B has a well-established role in polarized sorting of cargos to the basolateral membrane. Here we show that ß1 integrin was dependent on AP-1B and its coadaptor, autosomal recessive hypercholesterolemia protein (ARH), for sorting to the basolateral membrane. We further demonstrate an unprecedented role for AP-1B at the basal plasma membrane during collective cell migration of epithelial sheets. During wound healing, expression of AP-1B (and ARH in AP-1B-positive cells) slowed epithelial-cell migration. We show that AP-1B colocalized with ß1 integrin in focal adhesions during cell migration using confocal microscopy and total internal reflection fluorescence microscopy on fixed specimens. Further, AP-1B labeling in cell protrusions was distinct from labeling for the endocytic adaptor complex AP-2. Using stochastic optical reconstruction microscopy we identified numerous AP-1B-coated structures at or close to the basal plasma membrane in cell protrusions. In addition, immunoelectron microscopy showed AP-1B in coated pits and vesicles at the plasma membrane during cell migration. Lastly, quantitative real-time reverse transcription PCR analysis of human epithelial-derived cell lines revealed a loss of AP-1B expression in highly migratory metastatic cancer cells suggesting that AP-1B's novel role at the basal plasma membrane during cell migration might be an anticancer mechanism.

A gene signature for a long-term survivor of an atypical teratoid/rhabdoid tumor.

Atypical teratoid/rhabdoid tumors (AT/RTs) are aggressive brain tumors that are commonly associated with a dismal prognosis. However, there have been isolated reports of long-term survival that was not necessarily correlated with other prognostic factors such as age, clinical stage, or extent of surgical resection. Here, we report the case of a 6-year-old boy with AT/RT who remained disease-free for 8 years after undergoing subtotal surgical resection followed only by radiation therapy. On recurrence, the tumor rapidly progressed, leading to the patient's death a short time later. To further characterize this case and learn more about the tumor biology of long-term survivors, we compared the gene expression (GE) profiles from representative samples obtained from primary, recurrent, and progressive disease tumors of the above-mentioned patient along with a cohort of primary untreated AT/RT samples using cDNA microarrays. Global GE analysis and unsupervised hierarchical clustering showed the three events clustered together and distinctly apart from the rest of the samples. This indicates a GE background that is maintained throughout the course of the disease. This unique case suggests that there may be specific clinical characteristics associated with distinctive molecular subtypes of AT/RT. The identification and characterization of AT/RT subtypes could lead to advances in both prognosis and treatment of these tumors.

Study of the gene expression and microRNA expression profiles of malignant rhabdoid tumors originated in the brain (AT/RT) and in the kidney (RTK).

PURPOSE: Malignant rhabdoid tumors (MRT) can occur in a variety of anatomical sites. The most frequent locations are the brain, where they are named atypical teratoid/rhabdoid tumors (AT/RT), and the kidney, where they are named rhabdoid tumors of the kidney (RTK). MRTs at all sites are recognized as the same entity due to their similar morphology, aggressive behavior, and a common genetic abnormality, an inactivating mutation of the SMARCB1/INI-1/hSNF5/BAF47 gene. We aim to investigate potential molecular differences between AT/RT and RTK. METHODS: We analyzed the microRNA (miRNA) and gene expression (GE) profiles of 10 RTK, 13 AT/RT, and 2 human MRT cell lines (G401-RTK and MON-AT/RT). Illumina V2 MicroRNA Chips (Illumina, Inc., CA, USA) were used for miRNA analysis, and Illumina HT-12 whole genome expression arrays were used for GE analysis. RESULTS: The distribution of p values from GE showed a significant difference between RTK and AT/RT, with 20 % of the genes having p values ≤0.05 and the principal component analysis of the GE data showed separation between RTK and AT/RT. However, the miRNA expression failed to identify the different tumor groups. Among the 122 genes significantly differentially expressed between AT/RT and RTK, we found both genes related to brain development (i.e., FABP7, 22-fold increase in AT/RT) and genes related to kidney development (i.e., TCF21, sixfold increase in RTK). CONCLUSION: Based on our results, we hypothesized that although MRT are indeed the same tumor, independent of the site of origin, the GE differences reflect the influence of microenvironment over tumor development.

Histone deacetylases expression in atypical teratoid rhabdoid tumors.

PURPOSE: Atypical teratoid rhabdoid tumors (ATRTs) are rare, highly malignant central nervous system tumors that occur during infancy and early childhood. Their poor outcome and resistance to conventional chemotherapies and radiotherapy, urges the development of new therapies. Recent studies have evaluated the effects of histone deacetylase inhibitors (HDACi) as a new potential treatment for ATRTs. However, most HDACi act unselectively against all, or at least several, histone deacetylase (HDAC) family members. We hypothesized that specific HDAC family members are deregulated in ATRT and therefore a more selective class of HDACi would be beneficial to patients with ATRT. METHODS: To test our hypothesis, we evaluated the expression level of different HDAC family members in ATRTs. Eight ATRTs were compared to six medulloblastoma samples in regards to the level of expression of the 18 HDAC family members as determined by microarray gene expression profiling. RESULTS: HDAC1 was the only member of the HDAC family to be significantly differentially expressed in ATRTs (FC = 4.728; p value = 0.00003). CONCLUSIONS: A class of HDACi specifically targeting HDAC1 may allow for the desired therapeutic benefits with fewer side effects for children with ATRT.