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Oocyte quality control culls eggs with defects in meiosis. In mouse, oocyte death can be triggered by defects in chromosome synapsis and recombination, which involve repair of DNA double-strand breaks (DSBs) between homologous chromosomes. We show that RNF212, a SUMO ligase required for crossing over, also mediates oocyte quality control. Both physiological apoptosis and wholesale oocyte elimination in meiotic mutants require RNF212. RNF212 sensitizes oocytes to DSB-induced apoptosis within a narrow window as chromosomes desynapse and cells transition into quiescence. Analysis of DNA damage during this transition implies that RNF212 impedes DSB repair. Consistently, RNF212 is required for HORMAD1, a negative regulator of inter-sister recombination, to associate with desynapsing chromosomes. We infer that oocytes impede repair of residual DSBs to retain a "memory" of meiotic defects that enables quality-control processes. These results define the logic of oocyte quality control and suggest RNF212 variants may influence transmission of defective genomes.
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Dano ao DNA/genética , Reparo do DNA/genética , Oócitos/fisiologia , Animais , Proteínas de Ciclo Celular/genética , Pareamento Cromossômico/genética , Quebras de DNA de Cadeia Dupla , Feminino , Ligases/genética , Masculino , Meiose/genética , Camundongos , Controle de Qualidade , Recombinação Genética/genéticaRESUMO
A fracture liaison service is a systems-level multidisciplinary approach designed to reduce subsequent fracture risk in patients who recently sustained fragility fractures. It is estimated that one in three women and one in five men over the age of 50 years old have osteoporosis. Nonetheless, only 9 to 20% of patients who sustain an initial fragility fracture eventually receive any osteoporosis treatment. With the aim of preventing subsequent fractures, a fracture liaison service (FLS) works through identifying patients presenting with fragility fractures to the hospital and providing them with easier access to osteoporosis care through referrals for bone health and fracture risk assessment and recommendation or initiation of osteoporosis treatment. Currently, there are four major types of FLS models ranging from services that only identify at-risk patients and inform and educate the patient but take no further part in communicating their findings to other stakeholders in patients' care, to services that identify, investigate, and initiate treatment at the other end of the spectrum. In this article, we review the benefits, challenges, and outcomes of FLS in the American healthcare system with further exploration of the roles each member of the multidisciplinary team can play in improving patients' bone health.
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[Figure: see text].
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Arritmias Cardíacas/enzimologia , Glicemia/metabolismo , Sinalização do Cálcio , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Diabetes Mellitus Experimental/enzimologia , Miócitos Cardíacos/enzimologia , Processamento de Proteína Pós-Traducional , Potenciais de Ação , Adulto , Idoso , Animais , Arritmias Cardíacas/genética , Arritmias Cardíacas/fisiopatologia , Biomarcadores/sangue , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Estudos de Casos e Controles , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/genética , Acoplamento Excitação-Contração , Feminino , Glicosilação , Frequência Cardíaca , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Transgênicos , Pessoa de Meia-Idade , Mutação , Contração Miocárdica , NADPH Oxidase 2/genética , NADPH Oxidase 2/metabolismo , FosforilaçãoRESUMO
BACKGROUND: Orthopaedic surgery training programs have lagged behind other surgical specialties in increasing their representation of women and people from under-represented minority (URM) groups. Comparative data between orthopaedic surgery and other specialties are needed to help identify solutions to closing the diversity gap. QUESTIONS/PURPOSES: (1) Which surgical specialties have the greatest representation of women residents and residents from URM groups? (2) How have the proportions of women residents and residents from URM groups changed across the surgical specialties during the past decade? METHODS: This was a retrospective evaluation of a large, longitudinally maintained survey database. Resident data by gender and ethnicity were retrieved from the Accreditation Council for Graduate Medical Education Data Resource Books for the 2011 to 2012 through 2019 to 2020 academic years. The Accreditation Council for Graduate Medical Education database is updated annually; thus, it is the most up-to-date and complete database available for gender and ethnicity data for all surgical residents. Data were obtained and analyzed for seven different surgical specialties: orthopaedic surgery, neurosurgery, ophthalmology, otolaryngology, plastic surgery, general surgery, and urology. No sampling was necessary, and thus descriptive statistics of the data were completed. Because the entire population of residents was included for the period of time in question, no statistical comparisons were made, and the reported differences represent absolute differences between the groups for these periods. Linear regression analyses were performed to estimate the annual growth rates of women residents and residents from URM groups in each specialty. RESULTS: Among the seven surgical specialties, representation of women residents increased from 28% (4640 of 16,854) of residents in 2012 to 33% (6879 of 20,788) in 2020. Orthopaedic surgery had the lowest representation of women residents every year, with women residents comprising 16% of residents (700 of 4342) in 2020. Among the seven surgical specialties, representation of residents from URM groups increased from 8.1% (1362 of 16,854) in 2012 to 9.7% (2013 of 20,788) in 2020. In 2020, the representation of residents from URM groups in orthopaedic surgery was 7.7% (333 of 4342). In 2020, general surgery had the highest representation of women residents (42%; 3696 of 8809) as well as residents from URM groups (12%; 1065 of 8809). Plastic surgery (1.46% per year) and general surgery (0.95% per year) had larger annual growth rates of women residents than the other specialties did. In each surgical specialty, the annual growth rate of residents from URM groups was insignificant. CONCLUSION: During the past decade, there was only a small increase in the representation of women in orthopaedic surgery, while the representation of people from URM groups did not change. In contrast, by 2020, general surgery had become the most diverse among the seven surgical specialties. To increase diversity in our field, we need to evaluate and implement some of the effective interventions that have helped general surgery become the diverse surgical specialty that it is today. CLINICAL RELEVANCE: General surgery has substantially reduced gender and ethnic disparities that existed in the past, while those in orthopaedic surgery still persist. General surgery residencies have implemented a holistic review of resident applications and longitudinal mentoring programs to successfully address these disparities. Orthopaedic surgery programs should consider placing less emphasis on United States Medical Licensing Examination score thresholds and more weight on applicants' non-academic attributes, and put more efforts into targeted longitudinal mentorship programs, some of which should be led by non-minority faculty.
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Internato e Residência/tendências , Grupos Minoritários/estatística & dados numéricos , Ortopedia/educação , Médicas/estatística & dados numéricos , Especialidades Cirúrgicas/educação , Adulto , Bases de Dados Factuais , Educação de Pós-Graduação em Medicina , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Retrospectivos , Estados UnidosRESUMO
Background The United States Medical Licensing Exam (USMLE) Step 1 was recently changed from a numerically scored grading system to a pass/fail grading system. Until late 2024, there will be no formal studies about the impact that the grading change will have on the match process. To thoroughly assess the impact that this change will have on the overall match process, it is important to look at what the trends in applicants' objective measures have been in the years before the change. We aim to systematically evaluate the rates of change and mean trend of objective metrics found in residency applications in the main residency match. Methods Objective medical student data of matched and unmatched applicants were queried from the National Matching Program's Charting Outcomes in the Match Reports for the 2007 to 2020 application cycles. Data were used to create linear regression analyses and statistical tests were performed to evaluate trends over time. Results For matched applicants, there were statistically significant positive trends for the mean number of contiguous ranks (m=0.33, p<0.01), having another non-doctoral graduate degree (m=0.67, p<0.01), membership to Alpha Omega Alpha (AOA) honor society (m=0.22, p<0.01), mean USMLE Step 1 score (m=1.01, p<0.01), mean USMLE Step 2 score (m=1.68, p<0.01), mean number of research experiences (m=0.12, p<0.01), and mean number of abstracts, presentations, and publications (m=0.34, p<0.01). Additionally, there was a statistically significant negative trend for the percentage who graduated from a top 40 National Institutes of Health-funded medical school (m=-0.41, p<0.01). For unmatched applicants, there were statistically significant positive trends for having another non-doctoral graduate degree (m=0.83, p<0.01), mean USMLE Step 1 score (m=1.26, p<0.01), mean USMLE Step 2 score (m=2.27, p<0.01), mean number of research experiences (m=0.13, p<0.01), and mean number of abstracts, presentations, and publications (m=0.33, p<0.01). Conclusion Our study shows that there have been statistically significant increases in almost all objective measures in the residency application. Recent changes to the abstracts, presentations, and publications on the Step 1 scoring system will force almost all residency programs to overhaul their application process and potentially increase reliance on Step 2, research, and other nonobjective factors. For students early in their medical education, emphasis on Step 2 and research will yield increased chances of matching into residency in the future.
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INTRODUCTION: Adult spinal deformity (ASD) treatment for patients with osteoporosis presents a unique challenge for spine surgeons, particularly with ensuring adequate fixation and correction during surgery and due to the risk of treatment failure and complications thereafter. Osteoporosis is characterized by low bone mineral density (BMD) which may increase the risk for fractures. Approximately 12.6% of all adults over 50 years old in the United States are affected by osteoporosis, and the prevalence is predicted to increase with the aging population.1 ASD patients experience substantially higher rates of osteoporosis compared to the general population.2,3 One study discovered an osteoporosis prevalence of nearly 33% in a cohort of ASD patients undergoing long spinal fusion at two academic medical centers, with slightly over one- third of those patients receiving osteoporosis pharmacotherapy prior to surgery.3 Similarly, patients with osteoporosis experience ASD at higher rates than the general population, with one study finding that 9.5% of patients with osteoporosis suffer from ASD symptoms.3 Gupta et al. discovered that obtaining a DEXA scan of the forearm in addition to the hip allowed physicians to detect an additional 17% incidence of osteoporosis in ASD patients, suggesting that osteoporosis may be missed when there is only one DEXA scan available.4In addition to being potentially underdiagnosed and undertreated, ASD patients with osteoporosis experience higher rates of post-surgical complications. Pseudarthrosis, or nonunion after spinal fusion, is a painful and potentially debilitating complication following ASD surgery that ultimately requires additional surgical correction. Proximal junctional kyphosis (PJK), which is defined as proximal junctional sagittal Cobb angle ≥ 10° and at least 10° greater than the preoperative measurement, is another complication of ASD surgery.5 Though this condition may be clinically silent and manifest purely as a radiographic diagnosis, it is often a precursor to proximal junctional failure (PJF), a more severe form of PJK that ultimately increases the risk for intractable pain, neurological deficit, and revision surgery.6 ASD patients with osteoporosis experience significantly higher rates of pseudarthrosis, PJK, PJF, and postoperative fractures, as well as other forms of instrumentation failure requiring additional surgical treatment.7-11 This ultimately increases the pain, emotional burden, and morbidity experienced by patients. There is currently conflicting data regarding the impact of perioperative osteoporosis pharmacotherapy on outcomes in ASD patients. Bisphosphonates are considered first-line treatment for osteoporosis, though alternatives such as teriparatide, denosumab, and calcitonin may be used as well.12 Multiple studies have found that preoperative bisphosphonate treatment did not affect lumbar fusion nonunion rates.13,14 In contrast, a meta-analysis of randomized control trials found that postoperative bisphosphonates had no effect on lumbar fusion rates but did significantly reduce the risk of vertebral compression fracture (VCF) and pedicle screw loosening at 12-month follow-up.15 Prophylactic teriparatide treatment has been associated with improved BMD and lower incidence of PJK type-2 in osteoporosis patients who underwent ASD surgery.16 Evidence for perioperative treatment of teriparatide as a preventative step to increase fusion rates and reduce PJK and PJF is strongest.17 However, the percentage of ASD patients who are actually being treated perioperatively with these medications requires further evaluation, and a comparison of outcomes with osteoporosis and non-osteoporosis counterparts has yet to be explored. The purpose of this study was to evaluate the prevalence and treatment of osteoporosis among patients undergoing long spinal fusion for ASD, as well as compare the impact of osteoporosis treatment on surgical and radiographic outcomes following fusion surgery. Additionally, we sought to examine the differences in radiographic outcomes of osteoporotic patients receiving various pharmacologic regimens such as monotherapy vs combination therapy.
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Ossification of the posterior longitudinal ligament (OPLL) occurs as heterotopic bone forms in the posterior longitudinal ligament, resulting in neural compression, myelopathy, and radiculopathy. OPLL is most commonly observed in East Asian populations, with prevalence rates of 1.9% to 4.3% reported in Japan. OPLL rates are lower in North American and European patients, with reported prevalence of 0.1% to 1.7%. Patients typically develop symptoms due to OPLL in their cervical spines. The etiology of OPLL is multifactorial, including genetic, metabolic, and anatomic factors. Asymptomatic or symptomatic patients with OPLL can be managed nonsurgically, whereas patients with neurologic symptoms may require surgical decompression from an anterior, posterior, or combined approach. Surgical treatment can provide notable improvement in neurologic function. Surgical decision making accounts for multiple factors, including patient comorbidities, neurologic status, disease morphology, radiographic findings, and procedure complication profiles. In this study, we review OPLL epidemiology and pathophysiology, clinical features, radiographic evaluation, management, and complications.
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Ossificação do Ligamento Longitudinal Posterior , Fusão Vertebral , Vértebras Cervicais/cirurgia , Descompressão Cirúrgica/métodos , Humanos , Ligamentos Longitudinais/cirurgia , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Ossificação do Ligamento Longitudinal Posterior/terapia , Osteogênese , Fusão Vertebral/métodos , Resultado do TratamentoRESUMO
Objective: The objective of this retrospective study is to compare the fusion rates in anterior cervical discectomy and fusion surgery using freeze-dried versus fresh-frozen allografts. Methods: The study comprised 79 patients. Fifty-one patients received freeze-dried allograft (106 total spinal levels) and 28 patients received fresh-frozen allograft (50 total spinal levels). Fusion was assessed through trabecular bridging on follow-up anterior-posterior/lateral radiographs. Trabecular bridging was assessed on the superior and inferior borders of each spinal level and given a fusion grade. Complete fusion is defined as >50% bridging between superior and inferior borders of the bone graft; union is complete fusion in <26 weeks; delayed union is complete fusion after 26 weeks; and fibrous union is <50% bridging at ≥1 borders over 52 weeks. Results: All spinal levels reached complete fusion for both graft types. Of the freeze-dried treated cervical spinal levels, 77.35% (82/106) reached union (adequate trabecular bridging within 6 months) without delay compared with 80% (35/50) for the fresh-frozen bone graft group (P = 0.85). There was no significant difference in time-to-fusion analysis and no significant association between delayed union and any patient factors. In assessing Neck Disability Index (NDI), freeze-dried allografts did show a significantly greater decrease in NDI scores at 6 months (P = 0.03). At the 1 year follow-up, improvements in NDI were consistent in both allografts (P = 0.9647). Conclusions: From this study, freeze-dried and fresh-frozen allografts showed comparable rates of union, and both allografts can be used interchangeably for anterior cervical discectomy and fusion.
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Diffuse idiopathic skeletal hyperostosis (DISH) is an ankylosing condition affecting up to 32.5% of the general cohort. Although often asymptomatic, affected individuals may present with back pain, stiffness, dysphagia, functional decline, and neurologic deficits. Radiographically, DISH is characterized by flowing ossifications along the anterior spine spanning ≥4 vertebral bodies. Although the etiology of DISH remains unknown, diabetes mellitus and other metabolic derangements are strongly associated with DISH. Importantly, spinal ankylosis in DISH predisposes patients to unstable spine fractures from low-energy trauma, and careful consideration must be taken in managing these patients. This article reviews the epidemiology and pathophysiology of DISH, and its clinical findings, diagnostic criteria, and management.