Foot and ankle fellowship-trained osteopathic orthopaedic surgeons: a review, analysis, and understanding of current trends.

CONTEXT: Over the past several decades, orthopedic surgery has seen a substantial increase in the number of surgeons completing fellowship training. Doctors of Osteopathic Medicine (DOs) continue to advance their orthopedic education through subspecialty fellowship training. DOs have represented between approximately 6 % and 15 % of American Orthopaedic Foot and Ankle Society (AOFAS) fellows. Although historical representation has been considered strong, the fellowship match years 2020 and 2021 have seen a decline in osteopathic orthopedic surgeons participating in foot and ankle fellowships. This deviates from the recent trends of increasing participation across orthopedic subspecialities. OBJECTIVES: To investigate and review the trends of orthopedic foot and ankle fellowship training. METHODS: Data was reviewed from the AOFAS regarding number of fellows matched and degree obtained. Data from the Federation of State Medical Boards (FSMB), American Orthopaedic Foot and Ankle Society (AOFAS) and Association of American Medical Colleges (AAMC) were reviewed for physician trends and match statistics. RESULTS: Fellowship match years 2020 and 2021 have seen a decline in osteopathic orthopedic surgeons participating in foot and ankle fellowships, with only roughly 3% of AOFAS fellows being osteopathic trained. CONCLUSIONS: Orthopedic surgery has the highest rate of subspecialty training of all surgical specialties. Although there is hope for an increasing osteopathic presence in orthopedic surgery, recent literature has pointed to potential for continued bias in opportunities for osteopathic students. We hope that increased participation of osteopathic graduates in orthopedic surgery training programs will result in the continued expansion of osteopathic orthopedic surgeons completing fellowship training, including in foot and ankle surgery.

Metatarsal Fractures.

Metatarsal fractures are some of the most common fractures reported in the human body. Recent advances in surgical techniques and fixation have helped facilitate healing and improved outcomes for our patients. The treatment goals of metatarsal fractures are to maintain the metatarsal parabola, sagittal position of the metatarsal heads, and a congruent metatarsophalangeal joint. Most of these injuries can be treated nonoperatively, but displaced fractures require surgical intervention to preserve normal gait biomechanics.

Directed Attention and Habituation: Two Concepts Critical to Tinnitus Management.

PURPOSE: Directed attention and habituation are key concepts pertaining to clinical intervention for bothersome tinnitus. Directed attention is the strategy of distracting attention away from the tinnitus. Habituation is the process of learning to stop paying attention to stimuli that are irrelevant or meaningless. Although tinnitus may be intrusive, it usually does not reflect some underlying condition requiring medical attention. Tinnitus in most instances is therefore considered an irrelevant, meaningless stimulus that is best treated by facilitating habituation to the phantom sound. This tutorial describes directed attention and habituation and how they relate to major behavioral methods of tinnitus intervention. METHOD: Arguably, the four major behavioral methods of tinnitus intervention with the strongest research evidence are cognitive behavioral therapy (CBT), tinnitus retraining therapy (TRT), tinnitus activities treatment (TAT), and progressive tinnitus management (PTM). Each of these four methods was evaluated to determine the role of directed attention as a treatment strategy and habituation as a treatment goal. RESULTS: All four of the methods (CBT, TRT, TAT, and PTM) utilize some form of directed attention as a component of their counseling. Habituation is the explicit or implicit goal of each of these methods. CONCLUSIONS: Directed attention and habituation are essential concepts for all of the major methods of behavioral intervention for tinnitus that were studied. It would therefore seem appropriate to include directed attention as a universal treatment strategy for bothersome tinnitus. Likewise, the commonality of habituation as the objective of treatment would suggest that habituation should be the universal goal of any method that is intended to mitigate the emotional and functional effects of tinnitus.

Cardiac arrest in diving: The key to success.

This case report describes the successful management of an out-of-hospital arrest in a diver following a suspected arterial gas embolism (AGE). It illustrates both the inherent risks of diving and the importance of prompt and effective implementation of the "chain of survival" from bystanders. Rapid on-scene responses from paramedics and helicopter emergency medical services facilitated prompt evacuation to a Category 1 (multiplace) recompression chamber (RCC) where specialists in cardiology and hyperbaric medicine were available. Alternative causes of cardiac arrest were considered, with a presumed AGE successfully treated with multiple rounds of hyperbaric oxygen therapy. The key factors which led to this successful outcome are discussed, including early recognition and call for help, competent cardiopulmonary resuscitation, and direct evacuation to a Category 1 RCC, with additional consideration of the diagnosis leading to cardiac arrest. The case clearly illustrates the need for all those involved in diving regularly to be competent and confident in performing basic life support, as well as the awareness of the emergency services of the need for diving casualties to be treated at appropriate hyperbaric facilities. Were it not for the simple, prompt and effective treatment this diver received, both on scene and in hospital, it is highly unlikely that such a positive outcome would have been achieved.

Sound Therapy to Reduce Auditory Gain for Hyperacusis and Tinnitus.

PURPOSE: Hyperacusis is the most common of the different types of sound tolerance conditions. It has been defined as physical discomfort or pain when any sound reaches a certain level of loudness that would be comfortable for most people. Because hyperacusis and tinnitus occur together so often, it has been theorized that they have a common neural mechanism. A leading contender for that mechanism is enhancement of auditory gain. The purpose of this tutorial is to review the evidence that sound/acoustic therapy can reduce auditory gain and, thereby, can increase loudness tolerance for people with hyperacusis and/or suppress the percept of tinnitus. METHOD: The scientific literature was informally reviewed to identify and elucidate relationships between tinnitus, hyperacusis, sound therapy, and auditory gain. RESULTS: Evidence exists, both in animal and human studies, that enhanced auditory gain is associated with hyperacusis and tinnitus. Further evidence supports the theory that certain forms of sound therapy can reduce neural hyperactivity, thereby reducing auditory gain. The evidence for sound therapy reducing auditory gain is stronger for hyperacusis than it is for tinnitus. CONCLUSIONS: Based on results from numerous studies, sound therapy clearly has application as a method of desensitization for hyperacusis. Enhanced auditory gain might be responsible for tinnitus, but other mechanisms have been theorized. A review of the relevant literature leads to the conclusion that some form(s) of sound therapy has the potential to suppress or eliminate tinnitus on a long-term basis. Systematic research is needed to evaluate this premise.

Differences in Fourth-Year Orthopaedic Away Rotation Opportunities and Fees Among Osteopathic and Allopathic Medical Students 1 Year After the Implementation of the Single Accreditation System.

Fourth-year away rotations are well recognized as an important modifiable variable that has been shown to increase a student's opportunity to match into orthopaedic surgery. The purpose of this article was to determine whether allopathic (MD) and osteopathic (DO) medical students have equal opportunities for away rotations in terms of (1) eligibility and (2) fees associated with rotations after the single accreditation merger. Methods: A cross-sectional study was performed during the 2021 application cycle (April to November) by reviewing all nonmilitary, Accreditation Council for Graduate Medical Education-accredited orthopaedic surgery programs (n = 194). Each program's website, affiliated school of medicine's website, and visiting student applications service portal were searched. Eligibility criteria for an away rotation and associated fees were recorded. Results: Of the 194 programs, 18 (9.3%) of programs were found to have publicly published eligibility for away rotations that prohibited students based on applicant degree. Five (2.6%) programs/medical schools had fees that were larger for DO medical students compared with MD medical students ranging for $50 to $5,000. No programs/medical schools had larger fees for MD medical students compared with DO medical students. Conclusions: Although DO and MD degrees are equivalent degrees for licensing and credentialing and graduate medical education has transitioned to a single accrediting body, there remained discord in the opportunities for fourth-year away rotations between osteopathic and allopathic medical students. This study highlights the necessity for greater reform, consistency, and transparency among orthopaedic surgery residency programs and their affiliated institutions.

Reevaluating the Use of Sound Therapy for Tinnitus Management: Perspectives on Relevant Systematic Reviews.

PURPOSE: Tinnitus is a highly prevalent condition that can severely reduce health functioning. In spite of extant clinical practice guidelines (CPGs), implementation of these CPGs is relatively uncommon. As a result, patients seeking professional services for tinnitus often have no assurance of receiving evidence-based care. The purpose of this tutorial was to clarify the evidence for sound therapy so that it may be included in future CPGs for tinnitus. METHOD: "Best clinical evidence" is obtained from high-quality systematic reviews, which are generally considered the highest level of evidence. Our review of recent, comprehensive, high-quality systematic reviews of interventions for tinnitus concludes that cognitive behavioral therapy is the only effective intervention, though the strength of evidence was generally rated as low in these reviews. Although trials of sound therapy for tinnitus have been included in these reviews, they have been rated as having high risk of bias (RoB) and not included in syntheses or rated as insufficient strength of evidence. RESULTS: Conclusions from these and other reviews have influenced recommendations made in CPGs for tinnitus. These conclusions, however, can make it appear that an intervention for tinnitus is not effective, even if the opposite is true. We contend that the strict inclusion criteria for these reviews are counterproductive and have the effect of obscuring decades of evidence demonstrating the clinical effectiveness of sound therapies for tinnitus. Ultimately, this process has resulted in many patients not receiving sound therapy, despite what should be sufficient evidence that this is an effective form of intervention. CONCLUSION: If we rely on systematic reviews using contemporary RoB assessment criteria for studies published prior to these reporting guidelines, then we risk excluding important conclusions regarding interventions that could help patients in need.

Inflammatory myofibroblastic tumor of the larynx: Case report.

Inflammatory myofibroblastic tumor is usually a benign tumor of mesenchymal origin that is rarely found in the larynx. This case explores the unique laryngeal location and presentation of this tumor as well as the challenging radiographic and histologic findings.

Occupational Noise Exposure and Longitudinal Hearing Changes in Post-9/11 US Military Personnel During an Initial Period of Military Service.

OBJECTIVES: Auditory impairments, particularly those resulting from hazardous occupational noise exposures, are pressing concerns for the US Departments of Defense (DoD) and Veterans Affairs (VA). However, to date, no studies have estimated the rate of hearing threshold change that occurs during service or how changes may vary by military occupation. Hearing threshold changes during military service have historically been reported as the proportion of Service members demonstrating a significant threshold shift. This approach does not capture the rate of the hearing threshold change or the specific audiometric frequencies impacted. Determining the rate of hearing threshold change, and factors that affect the rate of change, is important to elucidate the impact of military service on hearing and to guide prevention strategies and subsequent hearing health care. Our primary objective was to estimate the annual rate of hearing threshold change during military service as a consequence of military occupational noise exposure ranking. DESIGN: We linked audiometric data, collected from military personnel as part of a DoD hearing conservation program, to data describing demographic and military-service characteristics obtained from individuals enrolled in the Noise Outcomes In Service members Epidemiology Study. The analytic cohort included Veterans who enlisted in military service after September 2001 (n = 246). We examined the longitudinal association between military occupations categorized as having a low, moderate, or high noise exposure ranking and pure-tone hearing thresholds (500 to 6000 Hz) using a hierarchical linear model. The average annual rate of hearing threshold change and their 95% confidence intervals were estimated by service branch, military occupational noise exposure ranking, and audiometric test frequency. RESULTS: On average, hearing threshold change ranged between -0.5 and 1.1 dB/year and changes over time varied by service branch, audiometric test frequency, and military occupation noise ranking. Generally, higher test frequencies (3000 to 6000 Hz) and military occupations with moderate or high noise exposure rankings had the greatest average annual rates of hearing threshold change; however, no dose-response relationship was observed. Among Marine Corps personnel, those exposed to occupations with high noise rankings demonstrated the greatest average annual rate of change (1.1 dB/year at 6000 Hz). Army personnel exposed to occupations with moderate noise rankings demonstrated the greatest average annual rate of change (0.6 dB/year at 6000 Hz). CONCLUSIONS: This study (1) demonstrates the unique use of DoD hearing conservation program data, (2) is the first analysis of hearing threshold changes over time using such data, and (3) adds to the limited literature on longitudinal changes in hearing. The difference in hearing threshold changes across military branches is likely indicative of their varying noise exposures, hearing protection device use and enforcement, and surveillance practices. Results suggest Marine Corps and Army personnel are at risk for hearing threshold changes and that, among Army personnel, this is most pronounced among those exposed to moderate levels of occupational noise exposure. Estimates of the rate of hearing threshold change by frequency and factors that impact hearing are useful to inform the DoD's efforts to protect the hearing of their Service members and to the Veterans Affairs's efforts to identify and rehabilitate those most likely to experience hearing threshold change.

Glomerular Disease in Temporal Association with SARS-CoV-2 Vaccination: A Series of 29 Cases.

Background: Immune responses to vaccination are a known trigger for a new onset of glomerular disease or disease flare in susceptible individuals. Mass immunization against SARS-CoV-2 in the COVID-19 pandemic provides a unique opportunity to study vaccination-associated autoimmune kidney diseases. In the recent literature, there are several patient reports demonstrating a temporal association of SARS-CoV-2 immunization and kidney diseases. Methods: Here, we present a series of 29 cases of biopsy-proven glomerular disease in patients recently vaccinated against SARS-CoV-2 and identified patients who developed a new onset of IgA nephropathy, minimal change disease, membranous nephropathy, ANCA-associated GN, collapsing glomerulopathy, or diffuse lupus nephritis diagnosed on kidney biopsies postimmunization, as well as recurrent ANCA-associated GN. This included 28 cases of de novo GN within native kidney biopsies and one disease flare in an allograft. Results: The patients with collapsing glomerulopathy were of Black descent and had two APOL1 genomic risk alleles. A brief literature review of patient reports and small series is also provided to include all reported cases to date (n=52). The incidence of induction of glomerular disease in response to SARS-CoV-2 immunization is unknown; however, there was no overall increase in incidence of glomerular disease when compared with the 2 years prior to the COVID-19 pandemic diagnosed on kidney biopsies in our practice. Conclusions: Glomerular disease to vaccination is rare, although it should be monitored as a potential adverse event.

CRISPR-TAPE: protein-centric CRISPR guide design for targeted proteome engineering.

Rational molecular engineering of proteins with CRISPR-based approaches is challenged by the gene-centric nature of gRNA design tools. To address this, we have developed CRISPR-TAPE, a protein-centric gRNA design algorithm that allows users to target specific residues, or amino acid types within proteins. gRNA outputs can be customized to support maximal efficacy of homology-directed repair for engineering purposes, removing time-consuming post hoc curation, simplifying gRNA outputs and reducing CPU times.

A Phase I Study of LY3009120, a Pan-RAF Inhibitor, in Patients with Advanced or Metastatic Cancer.

Mutations in ERK signaling drive a significant percentage of malignancies. LY3009120, a pan-RAF and dimer inhibitor, has preclinical activity in RAS- and BRAF-mutated cell lines including BRAF-mutant melanoma resistant to BRAF inhibitors. This multicenter, open-label, phase I clinical trial (NCT02014116) consisted of part A (dose escalation) and part B (dose confirmation) in patients with advanced/metastatic cancer. In part A, oral LY3009120 was dose escalated from 50 to 700 mg twice a day on a 28-day cycle. In part B, 300 mg LY3009120 was given twice a day. The primary objective was to identify a recommended phase II dose (RP2D). Secondary objectives were to evaluate safety, pharmacokinetics, and preliminary efficacy. Identification of pharmacodynamic biomarkers was exploratory. In parts A and B, 35 and 16 patients were treated, respectively (N = 51). In part A, 6 patients experienced eight dose-limiting toxicities. The RP2D was 300 mg twice a day. Common (>10%) any-grade drug-related treatment-emergent adverse events were fatigue (n = 15), nausea (n = 12), dermatitis acneiform (n = 10), decreased appetite (n = 7), and maculopapular rash (n = 7). The median duration of treatment was 4 weeks; 84% of patients completed one or two cycles of treatment. Exposures observed at 300 mg twice a day were above the preclinical concentration associated with tumor regression. Eight patients had a best overall response of stable disease; there were no complete or partial clinical responses. Despite adequate plasma exposure levels, predicted pharmacodynamic effects were not observed.

Aurora A-Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy.

Although Aurora A, B, and C kinases share high sequence similarity, especially within the kinase domain, they function distinctly in cell-cycle progression. Aurora A depletion primarily leads to mitotic spindle formation defects and consequently prometaphase arrest, whereas Aurora B/C inactivation primarily induces polyploidy from cytokinesis failure. Aurora B/C inactivation phenotypes are also epistatic to those of Aurora A, such that the concomitant inactivation of Aurora A and B, or all Aurora isoforms by nonisoform-selective Aurora inhibitors, demonstrates the Aurora B/C-dominant cytokinesis failure and polyploidy phenotypes. Several Aurora inhibitors are in clinical trials for T/B-cell lymphoma, multiple myeloma, leukemia, lung, and breast cancers. Here, we describe an Aurora A-selective inhibitor, LY3295668, which potently inhibits Aurora autophosphorylation and its kinase activity in vitro and in vivo, persistently arrests cancer cells in mitosis, and induces more profound apoptosis than Aurora B or Aurora A/B dual inhibitors without Aurora B inhibition-associated cytokinesis failure and aneuploidy. LY3295668 inhibits the growth of a broad panel of cancer cell lines, including small-cell lung and breast cancer cells. It demonstrates significant efficacy in small-cell lung cancer xenograft and patient-derived tumor preclinical models as a single agent and in combination with standard-of-care agents. LY3295668, as a highly Aurora A-selective inhibitor, may represent a preferred approach to the current pan-Aurora inhibitors as a cancer therapeutic agent.

Impact of Tinnitus on Military Service Members.

OBJECTIVES: The Noise Outcomes in Servicemembers Epidemiology (NOISE) Study is obtaining longitudinal data to evaluate the effects of noise and other exposures on auditory function in military personnel. A gap in the literature is the lack of studies concerning how active-duty Service members might be impacted by having tinnitus. The present study reports NOISE Study data that address this gap. METHODS: Data are reported from current Service members and recently-separated (within 2.5 years) Veterans, enabling a direct comparison of results between active and post-military samples. Data were collected from two sites: VA Portland Health Care System, Portland, OR and Department of Defense Hearing Center of Excellence, San Antonio, TX. Participants completed comprehensive audiometric testing and numerous questionnaires. RESULTS: Results are presented from n = 428 participants across the two sites, including 246 Veterans and 182 Service members. The data reveal that, for both Service members and Veterans, the presence of tinnitus has effects on job performance, concentration, anxiety, depression, and sleep. CONCLUSIONS: This study has revealed that, for these samples of study participants, tinnitus has an impact on military Service members that is comparable to how it affects Veterans who have completed their military service within the previous 2.5 years.

Adult-onset Rasmussen's Syndrome with associated cortical dysplasia.

We describe a 23-year-old woman with previous right temporal lobe surgeries for underlying cortical dysplasia, presenting with drug-resistant right hemispheric seizures and epilepsia partialis continua (EPC). After anti-seizure medication adjustments, she developed focal status epilepticus with progressive EEG and neuroimaging changes. Cerebrospinal fluid and serum autoimmune panels were negative except for an elevated serum acetylcholine-receptor antibody titer, but she underwent immunosuppressive therapy. Stereotactic-EEG evaluation demonstrated multifocal independent ictal patterns in the right hemisphere. Rasmussen's Syndrome was confirmed by brain biopsy, and a hemispherectomy was performed. This patient demonstrates the rare association of adult-onset EPC with cortical dysplasia, precipitously evolving into Rasmussen's Syndrome.

Aurora A Kinase Inhibition Is Synthetic Lethal with Loss of the RB1 Tumor Suppressor Gene.

Loss-of-function mutations in the retinoblastoma gene RB1 are common in several treatment-refractory cancers such as small-cell lung cancer and triple-negative breast cancer. To identify drugs synthetic lethal with RB1 mutation (RB1 mut), we tested 36 cell-cycle inhibitors using a cancer cell panel profiling approach optimized to discern cytotoxic from cytostatic effects. Inhibitors of the Aurora kinases AURKA and AURKB showed the strongest RB1 association in this assay. LY3295668, an AURKA inhibitor with over 1,000-fold selectivity versus AURKB, is distinguished by minimal toxicity to bone marrow cells at concentrations active against RB1 mut cancer cells and leads to durable regression of RB1 mut tumor xenografts at exposures that are well tolerated in rodents. Genetic suppression screens identified enforcers of the spindle-assembly checkpoint (SAC) as essential for LY3295668 cytotoxicity in RB1-deficient cancers and suggest a model in which a primed SAC creates a unique dependency on AURKA for mitotic exit and survival. SIGNIFICANCE: The identification of a synthetic lethal interaction between RB1 and AURKA inhibition, and the discovery of a drug that can be dosed continuously to achieve uninterrupted inhibition of AURKA kinase activity without myelosuppression, suggest a new approach for the treatment of RB1-deficient malignancies, including patients progressing on CDK4/6 inhibitors.See related commentary by Dick and Li, p. 169.This article is highlighted in the In This Issue feature, p. 151.

Cancer pain and neuropathic pain are associated with A ß sensory neuronal plasticity in dorsal root ganglia and abnormal sprouting in lumbar spinal cord.

Evidence suggests that there are both nociceptive and neuropathic components of cancer-induced pain. We have observed that changes in intrinsic membrane properties and excitability of normally non-nociceptive Aß sensory neurons are consistent in rat models of peripheral neuropathic pain and cancer-induced pain. This has prompted a comparative investigation of the intracellular electrophysiological characteristics of sensory neurons and of the ultrastructural morphology of the dorsal horn in rat models of neuropathic pain and cancer-induced pain. Neuropathic pain model rats were induced with a polyethylene cuff implanted around a sciatic nerve. Cancer-induced pain model rats were induced with mammary rat metastasis tumour-1 rat breast cancer or MATLyLu rat prostate cancer cells implanted into the distal epiphysis of a femur. Behavioural evidence of nociception was detected using von Frey tactile assessment. Aß-fibre low threshold mechanoreceptor neurons in both cancer-induced pain and neuropathic pain models exhibited slower dynamics of action potential genesis, including a wider action potential duration and lower action potential amplitude compared to those in control animals. Enhanced excitability of Aß-fibre low threshold mechanoreceptor neurons was also observed in cancer-induced pain and neuropathic pain models. Furthermore, both cancer-induced pain and neuropathic pain models showed abundant abnormal axonal sprouting in bundles of myelinated axons in the ipsilateral spinal laminae IV and V. The patterns of changes show consistency between rat models of cancer-induced pain and neuropathic pain. These findings add to the body of evidence that animal models of cancer-induced pain and neuropathic pain share features that may contribute to the peripheral and central sensitization and tactile hypersensitivity in both pain states.

Case of Lumbar Schwannoma Presenting with Isolated Signs and Symptoms of Intracranial Hypertension.

BACKGROUND: Hydrocephalus and intracranial hypertension are rare signs of spinal tumors when presenting in isolation, particularly with benign tumors. CASE DESCRIPTION: Herein reported is a case of a 53-year-old woman who presented with headache, blurry vision, communicating hydrocephalus, and intracranial hypertension. No primary intracranial pathology was identified, and there were no clinical signs or symptoms of intraspinal pathology. Lumbar puncture revealed elevated opening pressure, cerebrospinal fluid protein, and suspected tumor cells in the cerebrospinal fluid, thus prompting spinal imaging. A primary lumbar schwannoma was subsequently determined to underlie her symptoms, which resolved with tumor resection. CONCLUSIONS: Clinical suspicion of spinal pathology should be maintained in patients with unexplained intracranial hypertension, even in the absence of localizing signs of spinal pathology.

Primary Diffuse Large B-Cell Lymphoma in a Patient with Rubinstein-Taybi Syndrome: Case Report and Review of the Literature.

BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a rare, congenital syndrome that is known to be associated with neoplasms of various organ systems. Evaluation and treatment of such patients is challenging, given the cognitive delay and heterogeneity of pathologic presentations that define this syndrome. CASE DESCRIPTION: Presented here is a case of a patient with RSTS, diagnosed at birth, who presented with subtle symptoms of lethargy and a change in behavior. He was found to have a large (7.0-cm × 4.7-cm), right-sided brain mass that was eventually diagnosed as a primary central nervous system lymphoma. CONCLUSIONS: To the best of our knowledge, this is the first reported case of a primary central nervous system lymphoma presenting in a patient with RSTS. This was confirmed through microscopic and histologic studies. The large size attained by this mass in our patient highlights the increased scrutiny and surveillance needed to provide the best care for these patients. A multidisciplinary team approach is ideal as successful treatment of our patient using surgical debulking, appropriate chemotherapy, and close postoperative follow-up has resulted in an excellent clinical outcome.