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Recent studies have shown that global variation in body proportions is more complex than previously thought as some traits formerly associated with climate adaptation are better explained by geographic proximity and neutral evolutionary forces. While the recent incorporation of quantitative genetic methodologies has improved understanding of patterns related to climate in Africa, Europe, and the Americas, Asia remains underrepresented in recent and historic studies of body form. As ecogeographic studies tend to focus on male morphology, potential sex differences in features influenced by climate remain largely unexplored. Skeletal measurements encompassing the dimensions of the skull, pelvis, limbs, hands, and feet were collected from male (n = 459) and female (n = 442) remains curated in 13 collections across seven countries in East Asia (n = 901). Osteological data were analyzed with sex and minimum temperature as covariates adjusted by autosomal single-nucleotide polymorphism population genetic distance using univariate Bayesian linear mixed models, and credible intervals were calculated for each trait. Analysis supports a relationship between specific traits and climate as well as providing the magnitude of response in both sexes. After accounting for genetic distance between populations, greater association between climate and morphology was found in postcranial traits, with the relationship between climate and the skull limited primarily to breadth measurements. Larger body size is associated with colder climates with most measurements increasing with decreased temperature. The same traits were not always associated with climate for males and females nor correlated with the same intensity for both sexes. The varied directional association with climate for different regions of the skeleton and between the sexes underscores the necessity of future ecogeographic research to holistically evaluate body form and to look for sex-specific patterns to better understand population responses to environmental stresses.
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Clima , Crânio , Feminino , Masculino , Humanos , Teorema de Bayes , Crânio/anatomia & histologia , Deriva Genética , Clima FrioRESUMO
Alzheimer's disease is the most common cause of dementia and the only illness among the top 10 causes of death for which there is no disease-modifying therapy. The failure rate of clinical trials is very high, in part due to the premature translation of successful results in transgenic mouse models to patients. Extensive evidence suggests that dysregulation of innate immunity and microglia/macrophages plays a key role in Alzheimer's disease pathogenesis. Activated resident microglia and peripheral macrophages can display protective or detrimental phenotypes depending on the stimulus and environment. Toll-like receptors (TLRs) are a family of innate immune regulators known to play an important role in governing the phenotypic status of microglia. We have shown in multiple transgenic Alzheimer's disease mouse models that harnessing innate immunity via TLR9 agonist CpG oligodeoxynucleotides (ODNs) modulates age-related defects associated with immune cells and safely reduces amyloid plaques, oligomeric amyloid-ß, tau pathology, and cerebral amyloid angiopathy (CAA) while promoting cognitive benefits. In the current study we have used a non-human primate model of sporadic Alzheimer's disease pathology that develops extensive CAA-elderly squirrel monkeys. The major complications in current immunotherapeutic trials for Alzheimer's disease are amyloid-related imaging abnormalities, which are linked to the presence and extent of CAA; hence, the prominence of CAA in elderly squirrel monkeys makes them a valuable model for studying the safety of the CpG ODN-based concept of immunomodulation. We demonstrate that long-term use of Class B CpG ODN 2006 induces a favourable degree of innate immunity stimulation without producing excessive or sustained inflammation, resulting in efficient amelioration of both CAA and tau Alzheimer's disease-related pathologies in association with behavioural improvements and in the absence of microhaemorrhages in aged elderly squirrel monkeys. CpG ODN 2006 has been well established in numerous human trials for a variety of diseases. The present evidence together with our earlier, extensive preclinical research, validates the beneficial therapeutic outcomes and safety of this innovative immunomodulatory approach, increasing the likelihood of CpG ODN therapeutic efficacy in future clinical trials.
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Doença de Alzheimer/patologia , Encéfalo/patologia , Imunidade Inata/efeitos dos fármacos , Oligodesoxirribonucleotídeos/farmacologia , Envelhecimento/patologia , Doença de Alzheimer/imunologia , Peptídeos beta-Amiloides/imunologia , Peptídeos beta-Amiloides/metabolismo , Animais , Autoanticorpos/sangue , Autoanticorpos/imunologia , Encéfalo/efeitos dos fármacos , Angiopatia Amiloide Cerebral/patologia , Feminino , Imunidade Inata/imunologia , Oligodesoxirribonucleotídeos/imunologia , Saimiri , Receptor Toll-Like 9/agonistas , Proteínas tau/metabolismoRESUMO
BACKGROUND: There are various approaches to the distal humerus when managing a distal humeral fracture, and controversy exists regarding which approach is optimal. The purpose of this study was to report the outcomes of the triceps tongue (TT) approach when used for osteosynthesis of AO type 13-A, B, and C distal humeral fractures. Secondarily, we aimed to compare the outcomes of the TT approach vs. olecranon osteotomy (OO) when used for osteosynthesis of AO type 13-C distal humeral fractures. METHODS: We performed a retrospective review of patients with distal humeral fractures treated with open reduction-internal fixation by either a TT or OO approach between 2007 and 2019 at 2 separate institutions. TT patients with AO type 13-C fractures were matched to OO patients at a 1:1 ratio based on age, sex, and fracture characteristics. Surgical time, intraoperative blood loss, elbow motion, fracture union, complications, and Disabilities of the Arm, Shoulder and Hand scores were compared. RESULTS: A total of 28 patients treated with the TT approach were assessed, and the matched TT and OO cohorts each comprised 15 patients. The TT group showed less blood loss (119.3 mL vs. 268.5 mL, P = .03), had greater maximal flexion (126° vs. 116°, P = .03), and achieved a larger flexion-extension arc (108° vs. 93°, P = .05) than the OO group. In the OO cohort, 27% of patients had complications directly related to the OO, and OO patients had a higher rate of postoperative ulnar nerve neuritis (33% vs. 0%, P = .04). There was no difference in Disabilities of the Arm, Shoulder and Hand score (P = .08), procedure time (P = .2), total number of patients with ≥1 complication (P = .5), difficulty with union (P = .7), or number of patients requiring revision surgery (P = .7). CONCLUSIONS: The TT approach is a safe and effective approach for the treatment of distal humeral fractures. When compared with the OO approach for AO type 13-C fractures, the TT approach did not differ regarding functional outcomes but showed increased range of motion, decreased intraoperative blood loss, and a lower rate of postoperative ulnar nerve neuritis. The TT approach should be considered as a safe and reliable first-line approach for intra-articular distal humeral fractures because it allows adequate visualization of the articular surface, eliminates complications related to osteotomy including delayed union or nonunion and hardware failure or irritation, and allows for easy conversion to total elbow arthroplasty.
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Articulação do Cotovelo , Fraturas do Úmero , Fraturas Intra-Articulares , Olécrano , Osteotomia , Braço , Perda Sanguínea Cirúrgica , Articulação do Cotovelo/cirurgia , Fixação Interna de Fraturas/métodos , Humanos , Fraturas do Úmero/cirurgia , Fraturas Intra-Articulares/cirurgia , Neurite (Inflamação) , Olécrano/cirurgia , Osteotomia/métodos , Complicações Pós-Operatórias , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do Tratamento , Neuropatias UlnaresRESUMO
BACKGROUND: Predicting ultimate lower extremity length is important in the treatment of lower limb length discrepancy (LLD), congenital limb deficiency, and other etiologies. Utilizing skeletal age over chronological age improves the prediction of ultimate lower extremity length. The recently described modified Fels knee skeletal maturity system allows for skeletal age estimation via imaging always available in LLD patients. We sought to compare the accuracy of the modified Fels knee skeletal maturity system versus chronological age in ultimate limb length prediction of a modern adolescent clinical population. METHODS: The medical records of all patients treated at our institution over a 20-year period with unilateral lower extremity pathology and available lower extremity imaging before and after reaching skeletal maturity were reviewed. Skeletal maturity was defined radiographically by closed distal femoral, proximal tibial, and proximal fibular physes. The femoral, tibial, and lower extremity length was measured in all radiographs. The modified Fels knee skeletal maturity system was applied to all radiographs obtained before maturity to estimate skeletal age. The accuracy of 3 widely utilized lower extremity length prediction systems was compared when utilizing estimated Fels skeletal age versus chronological age inputs. RESULTS: A total of 245 radiographs (109 before maturity) from 43 patients were eligible for inclusion. On cross-sectional analysis, linear modeling using Fels skeletal ages was uniformly associated with higher (improved) R2 values than chronological age-based models. On longitudinal analysis, skeletal age mixed-effects models had significantly lower (improved) Akaike information criterion and Bayesian information criterion values than chronological age models in all cases. Cohen d values were also significantly different (P<0.05) for the skeletal age models compared with chronological age models in all cases. CONCLUSIONS: In the treatment of LLD, the modified Fels knee skeletal maturity system can be readily applied to available imaging to improve the prediction of ultimate femoral, tibial, and lower extremity length. This skeletal maturity system may have significant utility in the estimation of ultimate LLD and determination of appropriate timing of epiphysiodesis. LEVEL OF EVIDENCE: Level III.
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Joelho , Extremidade Inferior , Adolescente , Teorema de Bayes , Estudos Transversais , Humanos , Desigualdade de Membros Inferiores/diagnóstico por imagem , Desigualdade de Membros Inferiores/etiologia , Tíbia/diagnóstico por imagemRESUMO
Rationale: Acute cellular rejection (ACR) is common during the initial 3 months after lung transplant. Patients are monitored with spirometry and routine surveillance transbronchial biopsies. However, many centers monitor patients with spirometry only because of the risks and insensitivity of transbronchial biopsy for detecting ACR. Airway oscillometry is a lung function test that detects peripheral airway inhomogeneity with greater sensitivity than spirometry. Little is known about the role of oscillometry in patient monitoring after a transplant.Objectives: To characterize oscillometry measurements in biopsy-proven clinically significant (grade ≥2 ACR) in the first 3 months after a transplant.Methods: We enrolled 156 of the 209 double lung transplant recipients between December 2017 and March 2019. Weekly outpatient oscillometry and spirometry and surveillance biopsies at Weeks 6 and 12 were conducted at our center.Measurements and Main Results: Of the 138 patients followed for 3 or more months, 15 patients had 16 episodes of grade 2 ACR (AR2) and 44 patients had 64 episodes of grade 0 ACR (AR0) rejection associated with stable and/or improving spirometry. In 15/16 episodes of AR2, spirometry was stable or improving in the weeks leading to transbronchial biopsy. However, oscillometry was markedly abnormal and significantly different from AR0 (P < 0.05), particularly in integrated area of reactance and the resistance between 5 and 19 Hz, the indices of peripheral airway obstruction. By 2 weeks after biopsy, after treatment for AR2, oscillometry in the AR2 group improved and was similar to the AR0 group.Conclusions: Oscillometry identified physiological changes associated with AR2 that were not discernible by spirometry and is useful for graft monitoring after a lung transplant.
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Resistência das Vias Respiratórias/fisiologia , Rejeição de Enxerto/diagnóstico , Transplante de Pulmão , Oscilometria/métodos , Testes de Função Respiratória/métodos , Doença Aguda , Biópsia , Broncoscopia , Elasticidade , Volume Expiratório Forçado , Glucocorticoides/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/patologia , Rejeição de Enxerto/fisiopatologia , Humanos , Imunidade Celular , Metilprednisolona/uso terapêutico , EspirometriaRESUMO
BACKGROUND: Transolecranon distal humerus fractures are uncommon injuries. This is the first multipatient case series to describe outcomes and complications following transolecranon distal humerus fractures in the adult population. METHOD: Design: retrospective; setting: single level 1 trauma center; patients/participants: 16 patients; intervention: surgical management of transolecranon distal humerus fracture; main outcome measurement: Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire after a minimum of 12 months. RESULTS: A total of 16 patients with open (n = 12) or closed (n = 4) transolecranon distal humerus fractures were identified. Nine female and 7 male patients with a mean age of 47 years were included. Mechanisms of injury included motor vehicle collisions (n = 3), motorcycle crashes (n = 4), ground-level falls (n = 3), falls from height (n = 4), train collision (n = 1), and an industrial accident (n = 1). Seven patients (44%) presented with nerve injury. Patients underwent open reduction with internal fixation (n = 15), external fixation (n = 6), or both (n = 5). Additional surgeries were ultimately required in 11 patients (69%), with a mean of 3 surgeries to manage each patient's elbow injuries. All patients returned for at least 3 clinical follow-up visits; mean clinical follow-up was 15.8 months and mean radiographic follow-up was 12.3 months. Complications were observed in 15 patients (94%). Eleven patients (69%) had limited range of motion with a flexion arc of less than 100° at their last clinic visit. Seven patients (44%) developed deep wound infections requiring repeat débridement and intravenous antibiotics. Implant removal was performed in 10 patients (62.5%) because of infection (n = 5), symptomatic hardware (n = 4), or device failure (n = 1). Heterotopic ossification was seen in 8 patients (50%) and post-traumatic arthrosis in 4 (25%). Two patients (12.5%) required flap reconstruction for soft tissue defects. Nonunion occurred in 7 patients (44%). DASH scores were obtained for 10 patients (62.5%) at a mean of 3.8 years after injury. The mean DASH score was 40.2, ranging from 4.2 to 76.5. Among respondents, 7 (70%) were able to resume working, with an average DASH work module score of 25. CONCLUSION: Management of transolecranon distal humerus fractures remain a challenge for orthopedic surgeons. Complication rates, including deep infection and nonunion, are high, with frequent long-term functional limitations posed to the patient, as evidenced by DASH scores.
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Articulação do Cotovelo , Fraturas do Úmero , Feminino , Fixação Interna de Fraturas , Humanos , Fraturas do Úmero/cirurgia , Úmero , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Low concentrations of cardiac troponin (cTn) have been recommended for rapid rule-out of acute myocardial infarction (AMI). We examined the Beckman Coulter Access high-sensitivity cardiac troponin I (hs-cTnI) assay to identify a single test threshold that can safely rule out AMI. METHODS: This analysis used stored samples collected in 2 prospective observational studies. In all, 1871 patients presenting to a tertiary emergency department with symptoms of acute coronary syndrome had blood taken for measurement of cTnI on presentation. The endpoint was type 1 myocardial infarction (T1MI). Sensitivity and negative predictive value (NPV) were calculated for hs-cTnI values below the 99th percentile. RESULTS: Ninety-eight patients had T1MI (5.2%), and 638 (34.1%) patients had an hs-cTnI <2 ng/L (limit of detection), with sensitivity of 99.0% (95% CI, 94.4%-100%) and NPV of 99.8% (95% CI, 99.1%-100%). No hs-cTnI value above a concentration of 2 ng/L achieved sensitivity of 99%. However, an NPV of 99.5% was achieved at values <6 ng/L. A cutoff <6 ng/L enabled 1475 (78.8%) patients to be ruled out on presentation with sensitivity of 93.9% (95% CI, 87.1%-97.7%). CONCLUSIONS: A single baseline cTn <2 ng/L measured with the Access hs-cTnI assay performed well for rule-out of AMI. This cutoff concentration identified 99% of patients with AMI and could reduce the number of patients requiring lengthy assessment. A cutoff of <6 ng/L yielded a high NPV but missed more cases of AMI than would be acceptable to clinicians.
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Infarto do Miocárdio/diagnóstico , Troponina I/sangue , Adulto , Feminino , Humanos , Masculino , Infarto do Miocárdio/sangue , Sensibilidade e Especificidade , Adulto JovemRESUMO
STUDY OBJECTIVE: This diagnostic accuracy study describes the performance of 5 accelerated chest pain pathways, calculated with the new Beckman's Access high-sensitivity troponin I assay. METHODS: High-sensitivity troponin I was measured with presentation and 2-hour blood samples in 1,811 patients who presented to an emergency department (ED) in Australia. Patients were classified as being at low risk according to 5 rules: modified accelerated diagnostic protocol to assess patients with chest pain symptoms using troponin as the only biomarker (m-ADAPT), the Emergency Department Assessment of Chest Pain Score (EDACS) pathway, the History, ECG, Age, Risk Factors, and Troponin (HEART) pathway, the No Objective Testing Rule, and the new Vancouver Chest Pain Rule. Endpoints were 30-day acute myocardial infarction and acute coronary syndrome. Measures of diagnostic accuracy for each rule were calculated. RESULTS: Data included 96 patients (5.3%) with acute myocardial infarction and 139 (7.7%) with acute coronary syndrome. The new Vancouver Chest Pain Rule and No Objective Testing Rule had high sensitivity for acute myocardial infarction (100%; 95% confidence interval [CI] 96.2% to 100% for both) and acute coronary syndrome (98.6% [95% CI 94.9% to 99.8%] and 99.3% [95% CI 96.1% to 100%]). The m-ADAPT, EDACS, and HEART pathways also yielded high sensitivity for acute myocardial infarction (96.9% [95% CI 91.1% to 99.4%] for m-ADAPT and 97.9% [95% CI 92.7% to 99.7%] for EDACS and HEART), but lower sensitivity for acute coronary syndrome (≤95.0% for all). The m-ADAPT, EDACS, and HEART rules classified more patients as being at low risk (64.3%, 62.5%, and 49.8%, respectively) than the new Vancouver Chest Pain Rule and No Objective Testing Rule (28.2% and 34.5%, respectively). CONCLUSION: In this cohort with a low prevalence of acute myocardial infarction and acute coronary syndrome, using the Beckman's Access high-sensitivity troponin I assay with the new Vancouver Chest Pain Rule or No Objective Testing Rule enabled approximately one third of patients to be safely discharged after 2-hour risk stratification with no further testing. The EDACS, m-ADAPT, or HEART pathway enabled half of ED patients to be rapidly referred for objective testing.
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Síndrome Coronariana Aguda/diagnóstico , Eletrocardiografia , Infarto do Miocárdio/diagnóstico , Medição de Risco/métodos , Troponina I/sangue , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/epidemiologia , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/epidemiologia , Estudos Prospectivos , Queensland/epidemiologia , Reprodutibilidade dos Testes , Fatores de RiscoRESUMO
High fetal hemoglobin (HbF, α2 γ2 ) levels ameliorate the clinical manifestations of sickle cell disease and ß thalassemia. The mechanisms that repress HbF expression and silence γ-globin genes in adults are incompletely characterized and only a single HbF inducer, hydroxyurea, is approved for treatment, and only in patients with sickle cell disease. We identified SIRT1, a protein deacetylase, as a new inducer of γ-globin. SIRT1 knockdown decreased, while SIRT1 ectopic expression upregulated γ-globin gene (HBG) expression in primary human erythroid cells and in K562 cells. The small molecule SIRT1 activators SRT2104 and SRT1720 enhanced HBG expression in cord blood human erythroblasts and reactivated silenced HBG in adult human erythroblasts. Furthermore, SIRT1 binds in the ß-globin gene cluster locus control region (LCR) and HBG promoters, promotes the looping of the LCR to HBG promoter, and increases the binding of RNA polymerase II and H4K16Ac in the HBG promoter. SIRT1 suppressed the expression of the HBG suppressors BCL11A, KLF1, HDAC1 and HDAC2. Lastly, SIRT1 did not change the proliferation of human erythroid progenitor cells or the expression of differentiation marker CD235a. These data suggest that SIRT1 activates HBG expression through facilitating LCR looping to the HBG promoter, inhibiting the expression of transcriptional suppressors of HBG, and indirectly increasing histone acetylation in the HBG promoter. SIRT1 is a potential therapeutic target for γ-globin gene induction, and small molecule SIRT1 activators might serve as a lead compound for the development of new HbF inducers.
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Hemoglobina Fetal/genética , Regulação da Expressão Gênica , Sirtuína 1/metabolismo , Ativação Transcricional , gama-Globinas/genética , Diferenciação Celular/genética , Proliferação de Células/genética , Expressão Ectópica do Gene , Eritroblastos/metabolismo , Células Precursoras Eritroides/metabolismo , Eritropoese/genética , Hemoglobina Fetal/metabolismo , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos , Células K562 , Região de Controle de Locus Gênico , Especificidade de Órgãos/genética , Regiões Promotoras Genéticas , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sirtuína 1/genética , gama-Globinas/metabolismoRESUMO
Contact inhibition keeps cell proliferation in check and serves as a built-in protection against cancer development by arresting cell division upon cell-cell contact. Yet the complete mechanism behind this anti-cancer process remains largely unclear. Here we present SIRT1 as a novel regulator of contact inhibition. SIRT1 performs a wide variety of functions in biological processes, but its involvement in contact inhibition has not been explored to date. We used NIH3T3 cells, which are sensitive to contact inhibition, and H460 and DU145 cancer cells, which lack contact inhibition, to investigate the relationship between SIRT1 and contact inhibition. We show that SIRT1 overexpression in NIH3T3 cells overcomes contact inhibition while SIRT1 knockdown in cancer cells restores their lost contact inhibition. Moreover, we demonstrate that p27 protein expression is controlled by SIRT1 in contact inhibition. Overall, our findings underline the critical role of SIRT1 in contact inhibition and suggest SIRT1 inhibition as a potential strategy to suppress cancer cell growth by restoring contact inhibition.
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Comunicação Celular/genética , Inibição de Contato/genética , Inibidor de Quinase Dependente de Ciclina p27/genética , Sirtuína 1/genética , Animais , Divisão Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Regulação da Expressão Gênica , Humanos , Camundongos , Células NIH 3T3 , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/metabolismo , TransgenesRESUMO
Fracture-related infections are a challenging complication in orthopedic trauma that often necessitates multiple surgeries. Early administration of systemic antibiotics and surgical intervention remains the gold standard of care, but despite these measures, treatment failures can be as high as 35%. For these reasons, the introduction of local antibiotics at the site of at-risk fractures has increased over the past decade. This review looks at the various measures being used clinically including local antibiotic powder, polymethylmethacrylate, biodegradable substances, antibiotic-coated implants, and novel methods such as hydrogels and nanoparticles that have the potential for use in the future.
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Fraturas Ósseas , Osteomielite , Humanos , Antibacterianos/uso terapêutico , Osteomielite/cirurgia , Próteses e Implantes , Fraturas Ósseas/cirurgia , Fraturas Ósseas/complicaçõesRESUMO
BACKGROUND: Women continue to be underrepresented in orthopaedic surgery. This study seeks to evaluate gender diversity of faculty and trainees at foot and ankle surgery fellowship programs. METHODS: In this cross-sectional analysis of 49 US foot and ankle fellowship programs, all publicly available data on program faculty (as of July 2023) were collected, as well as data on current and past fellows between 2018 and 2024. RESULTS: Of 49 programs with 195 foot and ankle surgery faculty, 26.5% (n = 13) had at least 1 female on faculty, with only 8.2% (n = 4) having female fellowship directors. Female faculty made up 9.7% (n = 19) of foot and ankle surgery faculty overall. Of 307 total fellows identified within the 6-year period, 19.5% (n = 60) were female. Geographic distribution of programs was as follows: 29% (n = 14) Northeast, 31% (n = 15) South, 19% (n = 9) Midwest, and 21% (n = 10) West. Northeast programs made up 62% of all programs with female faculty, whereas Midwest programs made up the least at 8% (P = .048). Programs with female faculty had more female fellows from 2018 to 2024 than programs without female faculty (33.7% vs 14%, P < .001). CONCLUSION: Our findings suggest that females remain underrepresented in foot and ankle surgery fellowship director positions, despite an increasing proportion of females entering orthopaedic surgery. Foot and ankle surgery fellowship programs with female faculty had a higher number of female trainees; as such, diversification of foot and ankle fellowship departments may be an important factor in ongoing efforts to promote gender diversity within the specialty. LEVEL OF EVIDENCE: Level IV, observational cross-sectional analysis.
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Procedimentos Ortopédicos , Ortopedia , Feminino , Humanos , Masculino , Tornozelo/cirurgia , Estudos Transversais , Bolsas de EstudoRESUMO
BACKGROUND: It has been assumed that diabetic patients with peripheral neuropathy should not have pain associated with Charcot foot arthropathy. METHODS: During a 19-year period, 14 diabetic patients (15 feet) presented for treatment with pain following resolution of the acute phases of midfoot Charcot foot arthropathy. All were clinically plantigrade with plain radiographic evidence of bony union without deformity. Pain did not resolve with the use of appropriate therapeutic footwear. When used, CT scans uniformly demonstrated nonunion. RESULTS: All 14 patients had resolution of their presenting pain following successful arthrodesis. Nonunion was confirmed at surgery in all of the patients. One patient developed a fatal pulmonary embolus following removal of the external fixator. Two required late exostectomy for bony overgrowth at the surgical site of fusion for nonunion. CONCLUSION: This small series of patients would suggest that nonunion of the Charcot neuroarthropathy process was responsible for complaints of pain not able to be managed with therapeutic footwear. Successful arthrodesis resolved the pain. CT imaging may help identify a treatable source of pain in this population.
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BACKGROUND: Growing clinical interest in the treatment of acquired foot deformity due to diabetes-associated Charcot foot arthropathy has led to multiple reports of favorable clinical outcomes in patients when their acquired deformity is at the midfoot level. Clinical failures and less than optimal clinical outcomes are achieved when the deformity is at the hindfoot or ankle levels. METHODS: A retrospective review was performed of all patients who underwent surgical correction of diabetes-associated Charcot foot arthropathy with talocalcaneal dislocation over an 18-year period. Reduction of the talocalcaneal dislocation, and maintenance of the correction with percutaneous pins and circular external fixation after subtalar joint preparation for fusion, was used as the method of surgically achieving a clinically plantigrade foot. Clinical outcomes were based on resolution of infection, limb salvage, and the ability to ambulate with commercially available therapeutic footwear. RESULTS: Forty-three feet in 39 patients were included. A favorable clinical outcome was achieved in 32 of 43 feet (74%) with 26 (60%) considered to have an "excellent" result with minimal shoeing issues and 6 (14%) considered to have a "good" outcome based on their need for a custom shoe modification and/or some form of short ankle-foot orthosis. Eleven feet (26%) were judged to have a "poor" clinical outcome and among those 11 feet, 6 underwent partial, or whole-foot amputation, 2 had persistent wounds, and 5 required the use of a standard ankle foot orthosis or Charcot Restraint Orthotic Walker (CROW). CONCLUSION: Subtalar dislocation in Charcot arthropathy is a complex clinical problem. In our series, reduction and maintenance of the reduction after subtalar dislocation was essential for a favorable clinical outcome.
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Background: Gender disparity remains pervasive in orthopaedic surgery, which affects the research pursuits of orthopaedic surgeons. The purpose of this study was to characterize gender-related authorship trends of orthopaedic surgery residents, including evaluation of gender-concordant publication rates. Methods: An observational cross-sectional analysis of US orthopaedic surgery residency programs was performed. Information on residency programs and demographics of each cohort was collected. Publication metrics consisting of number of first and non-first author publications and H-indices were manually obtained for PGY-3 to PGY-5 residents attending the 25 programs ranked the highest for research output by Doximity. Gender of each resident and senior author was determined from institutional websites using photos, biographies, and preferred pronouns when available. Results: A total of 532 residents, 169 (31.8%) female and 363 (68.2%) male, were included for authorship analysis. Of them, 415 (78%) had at least one first author publication, which did not vary significantly by gender. Female residents had disproportionately fewer first author publications compared with their representation (22% vs. 31.8%, p < 0.00001). Female residents averaged fewer first and non-first author publications compared with male residents (2.8 vs. 4.6, p = 0.0003; 6.4 vs. 10, p = 0.0001 respectively). Despite fewer publications overall, a greater subset of publications by female residents were written in collaboration with a female senior author compared with publications by male residents (p < 0.0001). Male residents had a higher average H-index of 5.4 vs. 3.9 among female residents (p = 0.00007). Conclusion: Despite similar rates of first author publication among male and female residents, female residents had fewer publications overall, lower H-indices, and disproportionately fewer first author publications than would be expected given their representation. Findings from this study suggest that gender disparity in orthopaedic surgery extends to differences in research productivity as early as in residency. This may have negative implications on the career advancement of female orthopaedic surgeons. Additional work is needed to identify and understand biases in research productivity and career advancement, to promote more equitable strategies for academic achievement. Level of Evidence: IV.
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Synthetic biology is creating genetically engineered organisms at an increasing rate for many potentially valuable applications, but this potential comes with the risk of misuse or accidental release. To begin to address this issue, we have developed a system called GUARDIAN that can automatically detect signatures of engineering in DNA sequencing data, and we have conducted a blinded test of this system using a curated Test and Evaluation (T&E) data set. GUARDIAN uses an ensemble approach based on the guiding principle that no single approach is likely to be able to detect engineering with perfect accuracy. Critically, ensembling enables GUARDIAN to detect sequence inserts in 13 target organisms with a high degree of specificity that requires no subject matter expert (SME) review.
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DNA , Análise de Sequência de DNA , DNA/genéticaRESUMO
BACKGROUND: The occurrence of toxic shock syndrome from an intrauterine device (IUD) is very rare. OBJECTIVES: To raise awareness of the risk of toxic shock syndrome caused by an IUD, to educate others about when to suspect this complication, and to provide treatment recommendations. CASE REPORT: A 49-year-old woman presented to the Emergency Department in septic shock after complaining of 5 days of nausea, vomiting, and diarrhea. Physical examination findings included a diffusely tender and rigid abdomen with free fluid on bedside sonogram. She was found, on computed tomography of her abdomen and pelvis, to have an IUD with moderate ascites. The IUD was removed, and both her IUD and her blood cultures grew out group A Streptococcus. Despite aggressive medical management, which included multiple vasopressors and broad-spectrum antibiotics, she died from group A streptococcal sepsis, with the IUD as her most likely source. Her clinical presentation and laboratory findings meet the Centers for Disease Control and Prevention diagnostic criteria for streptococcal toxic shock syndrome. Her diagnosis was confirmed by autopsy. CONCLUSION: IUDs should be considered as a possible source of infection in patients with an IUD who present with symptoms consistent with toxic shock syndrome. These patients need to be aggressively managed with early surgical intervention.
Assuntos
Dispositivos Intrauterinos/efeitos adversos , Choque Séptico/etiologia , Infecções Estreptocócicas/etiologia , Streptococcus pyogenes , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade , Streptococcus pyogenes/isolamento & purificaçãoRESUMO
OBJECTIVE: To describe humerus shaft fractures after low-energy gunshot wound (GSW) and compare with blunt injuries. We hypothesized that nerve injury, infection, and fracture union would be similar. DESIGN: Retrospective. SETTING: Urban Level 1 trauma center. PATIENTS/PARTICIPANTS: Four hundred three patients were treated for a humeral shaft fracture over 18 years. Sixty-two patients sustained injury due to GSW. INTERVENTION: Primary open reduction and internal fixation was pursued in 59%, including 32% after GSW. MAIN OUTCOME MEASUREMENTS: Rates of nerve injury, infection, and fracture union. RESULTS: Patients with GSW were younger with a mean age of 30 years, more likely male (90%), with isolated injuries (84%), and less likely to have simple fractures (84%). Both groups experienced high rates of union (98% of GSW fractures vs. 99% of closed high-energy fractures). Deep infection occurred in 1 patient (1.6%) after GSW. Rates of deep infection in the closed and open blunt trauma fracture groups were similarly low at 1% and 4.5%, respectively. Nerve injury on presentation after GSW was more common than after low-energy and high-energy closed fractures (47% vs. 13% and 27%), but similar to blunt open fracture (52%). Despite higher rates of nerve injury, nerve recovery occurred at similarly high rates after both GSW and blunt injuries (78% vs. 86%). CONCLUSIONS: Nerve injuries are more common after GSW, but most recover without intervention. Infection is uncommon after GSW, and secondary unplanned operations are rare. Initial nonoperative care of most GSW humerus fractures, even with radial nerve injury at the time of presentation, seems appropriate. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Assuntos
Fraturas Fechadas , Fraturas Expostas , Fraturas do Úmero , Ferimentos por Arma de Fogo , Ferimentos não Penetrantes , Humanos , Masculino , Adulto , Ferimentos por Arma de Fogo/complicações , Ferimentos por Arma de Fogo/diagnóstico por imagem , Estudos Retrospectivos , Resultado do Tratamento , Fraturas do Úmero/complicações , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/epidemiologia , Úmero , Fixação Interna de Fraturas , Fraturas Expostas/cirurgia , Ferimentos não Penetrantes/complicaçõesRESUMO
Introduction: Humeral shaft fractures are common injuries treated by orthopaedic surgeons. The purpose of this study is to evaluate displaced diaphyseal humerus fractures and describe the incidence and characteristics associated with non or minimally displaced fracture line extension into the proximal metadiaphyseal region of the humerus. Methods and materials: All adult patients with diaphyseal humeral shaft fractures located within the distal two-thirds of the humeral shaft, treated at a single level I trauma institution between 2007 and 2020, were retrospectively identified. 202 patients with 203 fractures of the humeral shaft were included. Fracture patterns were classified according to AO/OTA classification and fracture line extension into the proximal metadiaphyseal region was evaluated on radiographs. Patient demographics, management details, and radiographic outcomes were obtained from review of the electronic medical record. Results: Of 203 diaphyseal humerus fractures, 11.8 % (n = 24) had non or minimally displaced proximal extension of their main fracture line. This included 43.7 % (n = 7) of all proximal third junction diaphyseal fractures, 10.7 % (n = 16) of all middle third diaphyseal fractures, and 2.6 % (n = 1) of all distal third diaphyseal fractures. Patients with proximal fracture extension were, on average, older (61.7 versus 44.4 years, p < 0.001), and a higher percentage were female (75 % versus 45.5 %, p < 0.01) compared to patients without fracture proximal extension. Fractures with proximal extension were all closed fractures (n = 24), were more often sustained from low-energy fall (87.5 % versus 35.2 %, p < 0.001), and were more often spiral type fractures (62.5 % versus 17.2 %). Fractures with proximal extension were more often treated non-operatively (58.3 % versus 42.1 %, p < 0.01), but were found to have a higher rate of nonunion after non-operative treatment (17.6 % versus 8.1 %) compared to fractures without proximal extension. All operatively treated fractures that had proximal metaphyseal extension were secured with a fixation construct to achieve fixation proximal to the extent of the fracture line, most often into the humeral head and neck. Operative management with proximal fixation into the humeral head was also pursued for a patient with nonunion, including persistent lucency of the proximal extension line, after failed non-operative treatment. Mean follow-up was 35.5 weeks (range: 0-607 weeks). Conclusions: Proximal fracture line extension in the setting of diaphyseal humerus fractures is not uncommon. Detection and consideration of this sometimes subtle finding is important when planning to treat these injuries operatively.
RESUMO
INTRODUCTION: Ballistic femur fractures are a common injury treated at United States civilian trauma centers. This study investigates the outcomes of these injuries by comparing the rates of infection, nonunion, secondary operations, and associated injuries from low-velocity gunshot (GSW) injuries with fractures sustained by blunt trauma. METHODS: A retrospective cohort comparative study was performed at a Level 1 trauma center. 345 patients with closed blunt or GSW femoral shaft fractures over 10 years were included. All were treated with intramedullary nail fixation. Superficial and deep infection, vascular injury, compartment syndrome, nonunion, and secondary operations were identified. RESULTS: 148 patients in the GSW group and 197 patients in the blunt trauma group had overall mean age 33.5 years and 80% were male. Deep infection rates were similar There were no nonunions in the GSW group, contrasted with 8 (4.4%) nonunions in the blunt trauma group (p = 0.02). The rate of compartment syndrome was higher in the GSW group (6.1% vs 0, p < 0.001). Arterial injury occurred in 9% following GSW (vs 0, p < 0.001). Overall, secondary unplanned procedure rates were the same: 8.1% for both groups. DISCUSSION: Ballistic femoral shaft fractures are often equated with open injuries; however, rates of infection and secondary operations closely mirror that of closed injuries resulting from blunt force trauma. Nonunions may be more common after blunt injury, and compartment syndrome and arterial injury are substantially more common following GSW, warranting careful clinical assessment. LEVEL OF EVIDENCE: Prognostic, level III.