Evaluation of Intramedullary Olecranon Screw Fixation for Simple Olecranon Fractures: A Biomechanical Study.

PURPOSE: The purpose of this study was to biomechanically evaluate the stability of the 6.5 mm intramedullary (IM) olecranon screw compared to locking compression plate fixation for Orthopedic Trauma Association/AO Foundation (OTA/AO) 2U1B1 olecranon fractures under cyclic range of motion of the elbow. METHODS: Twenty paired elbows were randomized to either IM olecranon screw or locking compression plate fixation of a simulated OTA/AO 2U1B1 fracture. Pullout strength was tested by increasing force applied to the triceps and proximal fragment. Fracture gap displacement was measured using differential variable reluctance transducers as the elbow was cycled through a 135° arc of motion using a servohydraulic testing system. RESULTS: Analysis of variance revealed significant interaction between group and load on fracture distraction after the 500th cycle in three settings: between the plate at 5-pound load and screw at 35-pound load, the screw at 5-pound load and screw at 35-pound load, and between the plate at 15-pound load and screw at 35-pound load. The difference in the rate of failure between plate (2 of 80 samples) and screw (4 of 80 samples) was not statistically significant. CONCLUSIONS: For OTA/AO 2U1B1 olecranon fractures, a single 6.5 mm IM olecranon screw demonstrated similar stability when compared to the locking compression plates throughout range of motion testing. CLINICAL RELEVANCE: From a biomechanical perspective, 6.5 mm IM screws and locking compression plates have similar ability to maintain fracture reduction following simulated elbow range of motion exercises in OTA/AO 2U1B1 fractures, giving surgeons another option in the management of these fractures.

Can a Blade-Stopping Mechanism on Circular Table Saws Reduce the Severity of Hand Injuries in Contact Scenarios? A Cadaveric Study.

PURPOSE: Table saws are commonly used woodworking tools that carry a substantial risk of injury. Blade-stopping technology has been developed and has the potential to reduce the frequency and severity of injury. This study aimed to evaluate this technology on human tissue and characterize the resulting injuries. METHODS: Twenty-seven fresh, frozen cadaveric specimen hands were used. Three scenarios were tested, with the specimen (1) moving forward ("forward"); (2) moving backward, such as in a kickback scenario ("reverse"); and (3) dropped from above the saw blade ("top"). Each scenario was tested at both slow (0.001 m/sec) and fast (forward: 0.6 m/sec; reverse: 0.5 m/sec; top: 2.4 m/sec) approach speeds. The severity of the injuries was characterized by anatomic evaluation and confirmed with radiographic evaluation. Injuries were classified as no laceration, superficial soft tissue injury, deep soft tissue injury, and bony injury. RESULTS: For the slow approach speed, the brake cartridge engaged in 100% of the trials for all 3 scenarios, and 100% of the specimens sustained no injuries. Forward testing at a fast approach speed revealed the brake cartridge engaged in 89% of the trials (injuries: 4 superficial, 2 deep, 3 bony). Reverse testing at a fast approach speed revealed the brake cartridge engaged in 11% of trials (injuries: 1 superficial, 8 bony). Top testing at a fast approach speed revealed the brake cartridge engaged in 89% of the trials (injuries: 9 bony). CONCLUSIONS: Modern blade-stopping technology did not prevent all traumatic hand injuries in fast approach speed scenarios, but it reduced the incidence and severity of injuries. The technology was more effective at low approach speed scenarios. CLINICAL RELEVANCE: The findings of this study provide information to help understand the factors that can prevent or reduce the severity of contact injuries (hand, finger, or thumb) for operators of table saws.

Thumb and Index Finger Amputation after Radial Artery Occlusion in a Patient with COVID-19.

The pathophysiology and predictability of radial artery thromboembolic events in patients with COVID-19 is not fully understood. We report a case of thumb and index finger gangrene and multiple digit amputations secondary to digital artery occlusion after radial artery cannulation in a patient admitted with COVID-19 pneumonia and encephalopathy. The exact association, causality, and potential hand manifestations in this patient population is unclear at this time, but is of particular interest in the current state of the pandemic.

Targeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network.

Ocular developmental anomalies (ODA) such as anophthalmia/microphthalmia (AM) or anterior segment dysgenesis (ASD) have an estimated combined prevalence of 3.7 in 10,000 births. Mutations in SOX2 are the most frequent contributors to severe ODA, yet account for a minority of the genetic drivers. To identify novel ODA loci, we conducted targeted high-throughput sequencing of 407 candidate genes in an initial cohort of 22 sporadic ODA patients. Patched 1 (PTCH1), an inhibitor of sonic hedgehog (SHH) signaling, harbored an enrichment of rare heterozygous variants in comparison to either controls, or to the other candidate genes (four missense and one frameshift); targeted resequencing of PTCH1 in a second cohort of 48 ODA patients identified two additional rare nonsynonymous changes. Using multiple transient models and a CRISPR/Cas9-generated mutant, we show physiologically relevant phenotypes altering SHH signaling and eye development upon abrogation of ptch1 in zebrafish for which in vivo complementation assays using these models showed that all six patient missense mutations affect SHH signaling. Finally, through transcriptomic and ChIP analyses, we show that SOX2 binds to an intronic domain of the PTCH1 locus to regulate PTCH1 expression, findings that were validated both in vitro and in vivo. Together, these results demonstrate that PTCH1 mutations contribute to as much as 10% of ODA, identify the SHH signaling pathway as a novel effector of SOX2 activity during human ocular development, and indicate that ODA is likely the result of overactive SHH signaling in humans harboring mutations in either PTCH1 or SOX2.

Types of trauma-related blame following interpersonal trauma.

OBJECTIVE: The Diagnostic and Statistical Manual of Mental Disorders (DSM) now includes trauma-related blame as a symptom of posttraumatic stress disorder (PTSD Criterion D3; American Psychiatric Association, 2013). To date, most blame research has utilized quantitative scales, primarily for self-blame, with little attention to other forms of blame. The aims of this study were to (a) identify the common blame types reported by interpersonal trauma survivors through open-ended statements, and (b) explore how well these blame types converge with the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) screener's blame item and total scores. METHOD: Using a mixed-method design, interpersonal trauma survivors (N = 132) completed the Life Events Checklist and the PCL-5. They also provided a written statement indicating why they believe their traumatic event occurred, which was later coded into types of blame by three independent raters. RESULTS: Five blame types emerged from survivors' statements: self, perpetrator, other, global, and circumstance. However, in most cases the presence or absence of each of the blame types was not reliably associated with posttraumatic distress. CONCLUSION: The findings suggest that trauma-related blame attributions are more nuanced than is typically measured and that factors such as the degree of distress caused by a particular blame attribution, or how believable the thought is to the survivor, might be more clinically meaningful than the specific content of the belief. Clinicians and researchers might benefit from the development of a more nuanced measure of trauma-related blame. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Asymptomatic Intraosseous Meningioma of the Humerus: A Case Report and Review of the Literature.

Meningiomas are the most common central nervous system tumor. They are typically benign neoplasms but may produce neurological symptoms due to mass effect. Meningiomas may also extend to extradural locations; however, these account for only a small percentage of all meningiomas. Most extradural meningiomas arise in intraosseous locations, usually within the cranial bones or vertebrae. However, this is a rare case of extradural extension of an asymptomatic intracranial meningioma to the proximal humerus in the absence of any musculoskeletal symptoms. To the best of our knowledge, this presentation of an extradural intraosseous meningioma has not previously been reported in the literature. We present a case of an incidental intraosseous meningioma in a 66-year-old man. This patient was initially being screened for metastasis of stage IA1 adenocarcinoma of the lung, and a positron emission tomography (PET) scan revealed a focus of activity in the proximal diaphysis of the right humerus suspicious for malignancy. The upper extremity magnetic resonance imaging (MRI) demonstrated an indeterminate lesion. Curettage of the humeral lesion revealed an intraosseous psammomatous meningioma without evidence of metastatic lung carcinoma. Our case report aims to illustrate the importance of considering alternative metastatic sources, such as intracranial meningioma, during the investigation of an indeterminate bony lesion. This is the first case to illustrate asymptomatic intraosseous meningioma in an appendicular skeletal location, highlighting the need for thorough source investigation.

Fracture of the Volar Ulnar Index Metacarpal Base: Literature Review.

Information regarding the management of intra-articular base fractures of the index metacarpal is scarce. Fractures of the base of the index metacarpal are rare because of the inherent stability of the joint. Of the handful of case reports on this injury, there appear to be 2 main patterns: fractures of the dorsal radial condyle and fractures of the volar ulnar condyle, which are attached to the extensor carpi radialis longus and flexor carpi radialis tendons, respectively. Although majority of previously reported volar fragment fractures were treated with Kirschner wire stabilization, we reported a case that was managed nonsurgically. The case presented is of a 70-year-old man with a fracture of the volar ulnar condyle of the base of the index metacarpal. Although he initially struggled with swelling of the hand and mobility of the fingers, he did well with nonsurgical management and regained full strength in his hand.

Wide-Awake Hand Surgery Has Its Benefits: A Study of 1,011 Patients.

Purpose: Wide-awake local anesthesia with no tourniquet has dramatically changed hand surgery practice. Using lidocaine with epinephrine and no tourniquet has allowed many procedures to be moved from the main operating room to an in-office procedure room. Previous studies have shown that using local anesthesia is safe and cost effective, with high patient satisfaction. This study evaluated patient satisfaction and complications for the first 1,011 elective hand surgeries performed using wide-awake anesthesia in an in-office procedure room. Methods: The first 1,011 patients who underwent elective hand surgery in an in-office procedure room were surveyed regarding their satisfaction. The patients were monitored for postoperative complications. Patient survey results and complications were logged in a database and analyzed. Results: Single-digit trigger finger release was the most common procedure performed (n = 582), followed by mass excision (n = 158), multiple-digit trigger finger releases (n = 109), and carpal tunnel release (n = 41). There were 43 (4.3%) superficial skin infections, with the majority seen in single-digit trigger finger releases (n = 27). There were no deep wound infections. All infections were managed nonsurgically with oral antibiotics and local wound care. Ninety-nine percent of the patients rated the in-office procedure room experience as the same as or better than a dental visit, would recommend wide-awake anesthesia to a friend or family member, and would undergo the procedure again. Using "lean and green" hand packs saved our institution more than $65,000 and saved 18.4 tons of waste during this study period. Conclusions: Surgical procedures performed with wide-awake local anesthesia with no tourniquet in an in-office procedure room can be performed safely with a low infection rate, are cost effective, and have high patient satisfaction. Clinical relevance: Minor hand surgery done in an in-office procedure room is safe, is cost effective, and has high patient satisfaction.

Small molecule inhibition of RAS/MAPK signaling ameliorates developmental pathologies of Kabuki Syndrome.

Kabuki Syndrome (KS) is a rare disorder characterized by distinctive facial features, short stature, skeletal abnormalities, and neurodevelopmental deficits. Previously, we showed that loss of function of RAP1A, a RAF1 regulator, can activate the RAS/MAPK pathway and cause KS, an observation recapitulated in other genetic models of the disorder. These data suggested that suppression of this signaling cascade might be of therapeutic benefit for some features of KS. To pursue this possibility, we performed a focused small molecule screen of a series of RAS/MAPK pathway inhibitors, where we tested their ability to rescue disease-relevant phenotypes in a zebrafish model of the most common KS locus, kmt2d. Consistent with a pathway-driven screening paradigm, two of 27 compounds showed reproducible rescue of early developmental pathologies. Further analyses showed that one compound, desmethyl-Dabrafenib (dmDf), induced no overt pathologies in zebrafish embryos but could rescue MEK hyperactivation in vivo and, concomitantly, structural KS-relevant phenotypes in all KS zebrafish models (kmt2d, kmd6a and rap1). Mass spectrometry quantitation suggested that a 100 nM dose resulted in sub-nanomolar exposure of this inhibitor and was sufficient to rescue both mandibular and neurodevelopmental defects. Crucially, germline kmt2d mutants recapitulated the gastrulation movement defects, micrognathia and neurogenesis phenotypes of transient models; treatment with dmDf ameliorated all of them significantly. Taken together, our data reinforce a causal link between MEK hyperactivation and KS and suggest that chemical suppression of BRAF might be of potential clinical utility for some features of this disorder.

Replicative stress induces intragenic transcription of the ASE1 gene that negatively regulates Ase1 activity.

Intragenic transcripts initiate within the coding region of a gene, thereby producing shorter mRNAs and proteins. Although intragenic transcripts are widely expressed [1], their role in the functional regulation of genes remains largely unknown. In budding yeast, DNA replication stress activates the S phase checkpoint that stabilizes replication forks and arrests cells in S phase with a short spindle [2-4]. When yeast cells were treated with hydroxyurea (HU) to block DNA synthesis and induce replication stress, we found that Ase1, a conserved spindle midzone protein [5], appeared as two short protein isoforms in addition to the full-length protein. We further demonstrated that the short isoforms result from intragenic transcription of ASE1, which depends on the S phase checkpoint. Blocking generation of the short isoforms leads to a destabilized S phase spindle, characterized by increased spindle dynamics and frequent spindle collapse. Because the short Ase1 isoforms localize at the spindle in HU-treated cells and overexpression of the short Ase1 isoforms impairs the spindle midzone localization of full-length Ase1, it is likely that the presence of short Ase1 isoforms stabilizes the spindle by antagonizing full-length Ase1. Together, our results reveal intragenic transcription as a unique mechanism to downregulate gene functions in response to DNA replication stress.

The current view for the silencing of the spindle assembly checkpoint.

Chromosome bipolar attachment is achieved when sister kinetochores are attached by microtubules emanating from opposite spindle poles, and this process is essential for faithful chromosome segregation during anaphase. A fundamental question in cell biology is how cells ensure that chromosome segregation only occurs after bipolar attachment. It is well documented that unattached kinetochores activate the spindle assembly checkpoint (SAC) to delay chromosome segregation. Therefore, the silencing of the SAC is thought to trigger anaphase onset, but how correct chromosome attachment is coupled with SAC silencing and the subsequent anaphase onset is poorly understood. The establishment of chromosome bipolar attachment not only results in the occupancy of kinetochores by microtubules but also applies tension on sister kinetochores. A long-standing debate is whether the kinetochore attachment (occupancy) or the tension silences the SAC. Recent work in budding yeast reveals the SAC silencing network SSN that prevents SAC silencing prior to tension generation at kinetochores. Therefore, this signaling pathway ensures that SAC silencing and the subsequent anaphase onset occur only after chromosome bipolar attachment applies tension on chromosomes. This review will summarize the recent advances in the understanding of the SAC silencing process.

BCL6 canalizes Notch-dependent transcription, excluding Mastermind-like1 from selected target genes during left-right patterning.

Although the Notch signaling pathway is one of the most intensely studied intracellular signaling pathways, the mechanisms by which Notch signaling regulates transcription remain incompletely understood. Here, we report that B cell leukemia/lymphoma 6 (BCL6), a transcriptional repressor, is a Notch-associated factor. BCL6 is necessary to maintain the expression of Pitx2 in the left lateral plate mesoderm during the patterning of left-right asymmetry in Xenopus embryos. For this process, BCL6 forms a complex with BCL6 corepressor (BCoR) on the promoters of selected Notch target genes such as enhancer of split related 1. BCL6 also inhibits the transcription of these genes by competing for the Notch1 intracellular domain, preventing the coactivator Mastermind-like1 (MAM1) from binding. These results define a mechanism restricting Notch-activated transcription to cell-type-appropriate subsets of target genes, and elucidate its relevance in vivo during left-right asymmetric development.