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1.
Am J Hum Genet ; 110(4): 703-714, 2023 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-36990085

RESUMEN

GATA3 is essential for T cell differentiation and is surrounded by genome-wide association study (GWAS) hits for immune traits. Interpretation of these GWAS hits is challenging because gene expression quantitative trait locus (eQTL) studies lack power to detect variants with small effects on gene expression in specific cell types and the genome region containing GATA3 contains dozens of potential regulatory sequences. To map regulatory sequences for GATA3, we performed a high-throughput tiling deletion screen of a 2 Mb genome region in Jurkat T cells. This revealed 23 candidate regulatory sequences, all but one of which is within the same topological-associating domain (TAD) as GATA3. We then performed a lower-throughput deletion screen to precisely map regulatory sequences in primary T helper 2 (Th2) cells. We tested 25 sequences with ∼100 bp deletions and validated five of the strongest hits with independent deletion experiments. Additionally, we fine-mapped GWAS hits for allergic diseases in a distal regulatory element, 1 Mb downstream of GATA3, and identified 14 candidate causal variants. Small deletions spanning the candidate variant rs725861 decreased GATA3 levels in Th2 cells, and luciferase reporter assays showed regulatory differences between its two alleles, suggesting a causal mechanism for this variant in allergic diseases. Our study demonstrates the power of integrating GWAS signals with deletion mapping and identifies critical regulatory sequences for GATA3.


Asunto(s)
Elementos de Facilitación Genéticos , Factor de Transcripción GATA3 , Hipersensibilidad , Secuencias Reguladoras de Ácidos Nucleicos , Linfocitos T , Humanos , Alelos , Factor de Transcripción GATA3/genética , Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Hipersensibilidad/genética , Mapeo Cromosómico , Eliminación de Gen
2.
J Virol ; 97(12): e0133023, 2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-37966249

RESUMEN

IMPORTANCE: The essential steps of successful gene delivery by recombinant adeno-associated viruses (rAAVs) include vector internalization, intracellular trafficking, nuclear import, uncoating, double-stranded (ds)DNA conversion, and transgene expression. rAAV2.5T has a chimeric capsid of AAV2 VP1u and AAV5 VP2 and VP3 with the mutation A581T. Our investigation revealed that KIAA0319L, the multiple AAV serotype receptor, is not essential for vector internalization but remains critical for efficient vector transduction to human airway epithelia. Additionally, we identified that a novel gene WDR63, whose cellular function is not well understood, plays an important role in vector transduction of human airway epithelia but not vector internalization and nuclear entry. Our study also discovered the substantial transduction potential of rAAV2.5T in basal stem cells of human airway epithelia, underscoring its utility in gene editing of human airways. Thus, the knowledge derived from this study holds promise for the advancement of gene therapy in the treatment of pulmonary genetic diseases.


Asunto(s)
Bronquios , Dependovirus , Epitelio , Técnicas de Transferencia de Gen , Vectores Genéticos , Transducción Genética , Humanos , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Dependovirus/genética , Dependovirus/metabolismo , ADN , Epitelio/metabolismo , Epitelio/virología , Técnicas de Transferencia de Gen/tendencias , Terapia Genética/métodos , Vectores Genéticos/genética , Bronquios/metabolismo , Bronquios/virología , Transporte Activo de Núcleo Celular , Edición Génica/tendencias
3.
Arthroscopy ; 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38395270

RESUMEN

PURPOSE: To report return-to-sport rates, postoperative patient-reported outcomes (PROs), complication rates, and reoperation rates of a cohort of patients undergoing particulated juvenile articular cartilage (PJAC) allograft transplantation for patellofemoral articular cartilage defects. METHODS: We performed a single-institution retrospective review of all patients with patellofemoral articular cartilage defects who received PJAC allograft transplantation from 2014 to 2022. Baseline demographic characteristics and surgical data, including concomitant surgical procedures, were collected. Clinical outcomes recorded included return-to-sport rates, complications, reoperations, and the following PRO scores: Kujala knee score, Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference score, and PROMIS Physical Function score. RESULTS: Forty-one knees with a mean age of 23.4 ± 9.7 years and mean follow-up period of 30.3 months (range, 12-107 months) were included. The mean postoperative PROMIS Pain Interference, PROMIS Physical Function, and Kujala knee scores were 47.4 ± 7.7, 52.2 ± 10.8, and 81.7 ± 16.1, respectively, reflecting low residual anterior knee pain and a return to normal function. For patients playing organized sports at the high school and collegiate levels, the overall return-to-sport rate was 100% (17 of 17). During follow-up, complications developed in 12 knees (29.3%), the most common of which was anterior-based knee pain, and 6 knees (14.6%) required a total of 8 reoperations, which occurred from 6 to 32 months postoperatively. CONCLUSIONS: The 100% return-to-sport rate and satisfactory PRO scores in our study suggest that PJAC allograft transplantation can effectively address patellofemoral cartilage defects in many patients. The complication and reoperation rates of 29.3% and 14.6%, respectively, are consistent with the challenging and heterogeneous etiology and treatment of patellofemoral articular defects. LEVEL OF EVIDENCE: Level IV, case series.

4.
J Arthroplasty ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39127311

RESUMEN

BACKGROUND: Cementless total knee arthroplasty (TKA) is rising in popularity. The literature supporting its use over cemented TKA remains sparse. Using the Canadian Joint Replacement Registry (CJRR), we sought to investigate cementless versus cemented fixation in modern primary TKA and (1) determine whether there is an overall difference in revision by fixation, (2) perform a subanalysis of the most-commonly used cementless TKA brand in Canada, and (3) identify the reasons for revision. METHODS: The CJRR data was used to analyze TKA designs with cemented and cementless versions. Revision risk is reported as all-cause cumulative percent revision (CPR). Reasons for revision were analyzed. Cox proportional hazards models were used to report adjusted hazard ratios (HR) controlling for age, sex, patella resurfacing, and bearing constraints. We included 202,880 primary TKAs performed between 2012 and 2021. Of those, 9,163 (4.5%) were cementless. RESULTS: The CPR at 8 years was 4.49% for cementless and 3.14% for cemented implants. After adjusting for confounders, we did not detect a difference in revision risk overall (HR 0.87 [95% CI (confidence interval) 0.73 to 1.04], P = 0.128). However, the most commonly used cementless TKA brand demonstrated a CPR of 1.95% compared to 2.19% for its cemented version at 4 years. Furthermore, we detected a significantly lower revision risk compared to its cemented version after adjusting for confounders (HR 0.66 [95% CI 0.51 to 0.85], P = 0.001). The 4 most common reasons for revision in both groups were the following: (1) infection, (2) instability, (3) aseptic loosening, and (4) pain of unknown origin. CONCLUSIONS: Using CJRR data adjusted for confounding factors, no difference in revision risk was detected between cemented and cementless implants overall. However, for the most common brand of cementless TKA used in Canada, there was a lower risk of revision than its corresponding cemented version. The reasons for revision were similar.

5.
Pediatr Emerg Care ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39173273

RESUMEN

ABSTRACT: Distal forearm fractures are frequently encountered in the pediatric emergency department and often require reduction. Procedural sedation is commonly used to facilitate reduction of these injuries, although it can be associated with potentially severe complications, particularly in patients with cardiorespiratory comorbidities. The ultrasound-guided hematoma block has been gaining popularity as an analgesic alternative in adult patients, but literature supporting its use in pediatric patients is limited. We describe a point-of-care ultrasound-guided hematoma block used to facilitate successful reduction of a distal radius fracture in an adolescent patient with a history of a difficult airway for whom procedural sedation would have posed considerable risk.

6.
Can J Surg ; 67(4): E300-E305, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39089818

RESUMEN

BACKGROUND: Patients aged 40-60 years who require total hip arthroplasty (THA) often first receive unindicated hip arthroscopy or magnetic resonance imaging (MRI). Our objective was to identify potentially inappropriate resource utilization before THA, specifically reporting on the proportion of patients aged 40-60 years who underwent hip arthroscopy or MRI in the year before THA. METHODS: We conducted a retrospective, population-based study at the provincial level. We retrieved data from the Canadian Institute for Health Information (CIHI). We included all Ontario residents who underwent an elective, primary THA for osteoarthritis between Apr. 1, 2004, and Mar. 31, 2016. We identified the rates and timing of patients who underwent an MRI or hip arthroscopy before their index THA. RESULTS: The percentage of patients who underwent an MRI before THA increased significantly over the study period, from 8.7% in 2004 to 23.8% in 2015. There was also a significant but variable trend in the percentage of patients who underwent a hip arthroscopy before THA. CONCLUSION: Our results demonstrate a high, gradually increasing proportion of patients who received a hip MRI and a low but increasing proportion of patients who received hip arthroscopy in close proximity to THA. Multidisciplinary collaboration may improve knowledge translation and help reduce the rate of clinically unnecessary diagnostic and therapeutic interventions in this population of patients who require THA.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Artroscopía , Imagen por Resonancia Magnética , Osteoartritis de la Cadera , Procedimientos Innecesarios , Humanos , Osteoartritis de la Cadera/cirugía , Persona de Mediana Edad , Artroplastia de Reemplazo de Cadera/estadística & datos numéricos , Estudios Retrospectivos , Adulto , Femenino , Artroscopía/estadística & datos numéricos , Masculino , Ontario , Procedimientos Innecesarios/estadística & datos numéricos
7.
Mol Cell ; 59(2): 188-202, 2015 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-26166704

RESUMEN

Enhancers instruct spatio-temporally specific gene expression in a manner tightly linked to higher-order chromatin architecture. Critical chromatin architectural regulators condensin I and condensin II play non-redundant roles controlling mitotic chromosomes. But the chromosomal locations of condensins and their functional roles in interphase are poorly understood. Here we report that both condensin complexes exhibit an unexpected, dramatic estrogen-induced recruitment to estrogen receptor α (ER-α)-bound eRNA(+) active enhancers in interphase breast cancer cells, exhibiting non-canonical interaction with ER-α via its DNA-binding domain (DBD). Condensins positively regulate ligand-dependent enhancer activation at least in part by recruiting an E3 ubiquitin ligase, HECTD1, to modulate the binding of enhancer-associated coactivators/corepressors, including p300 and RIP140, permitting full eRNA transcription, formation of enhancer:promoter looping, and the resultant coding gene activation. Collectively, our results reveal an important, unanticipated transcriptional role of interphase condensins in modulating estrogen-regulated enhancer activation and coding gene transcriptional program.


Asunto(s)
Adenosina Trifosfatasas/metabolismo , Proteínas de Unión al ADN/metabolismo , Elementos de Facilitación Genéticos , Receptor alfa de Estrógeno/metabolismo , Complejos Multiproteicos/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adenosina Trifosfatasas/antagonistas & inhibidores , Adenosina Trifosfatasas/genética , Secuencia de Bases , Sitios de Unión , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Cromatina/genética , Cromatina/metabolismo , ADN de Neoplasias/genética , Proteínas de Unión al ADN/antagonistas & inhibidores , Proteínas de Unión al ADN/genética , Estradiol/metabolismo , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Interfase , Células MCF-7 , Modelos Biológicos , Datos de Secuencia Molecular , Complejos Multiproteicos/antagonistas & inhibidores , Complejos Multiproteicos/genética , Proteínas Nucleares/metabolismo , Proteína de Interacción con Receptores Nucleares 1 , Regiones Promotoras Genéticas , Unión Proteica , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación
8.
J Arthroplasty ; 38(7S): S83-S88.e2, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37100095

RESUMEN

BACKGROUND: Contemporary total hip arthroplasty (THA) has resolved many implant longevity concerns in younger patients. Patients in their fourth and fifth decades of life are projected to be the fastest-growing demographic of THA patients. We aimed to assess this demographic to: 1) evaluate the rate of THA over time; 2) evaluate the cumulative incidence of revision; and 3) identify risk factors for revision. METHODS: A retrospective population-based study of patients between 40 and 60 years old undergoing primary THA was conducted using administrative data from a large clinical data repository. A total of 28,414 patients were included for analysis with a mean age of 53 years (range, 40-60 years) and median follow-up of 9 years (range, 0-17 years). Linear regressions were used to assess annual rates of THA in this cohort over time. Kaplan-Meier analysis was used to determine cumulative incidence of revision. Multivariate Cox proportional hazards models were used to determine association of variables with revision risk. RESULTS: The annual rate of THA in our population increased by 60.7% over the study period (P < .0001). Cumulative incidence of revision was 2.9% at 5 years and 4.8% at 10 years. Younger age, women, non-osteoarthritis diagnosis, medical complications, and annual surgeon volume ≤ 60 THA were associated with increased revision risk. CONCLUSION: Demand for THA continues to dramatically increase in this cohort. Risk of revision was low but multiple risk factors were identified. Future studies will help delineate the effect of these variables on revision risk and assess implant survivorship beyond 10 years.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Humanos , Femenino , Persona de Mediana Edad , Adulto , Artroplastia de Reemplazo de Cadera/efectos adversos , Prótesis de Cadera/efectos adversos , Estudios Retrospectivos , Falla de Prótesis , Reoperación/efectos adversos , Factores de Riesgo , Diseño de Prótesis , Resultado del Tratamiento
9.
J Clin Ultrasound ; 51(9): 1622-1630, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37850556

RESUMEN

This scoping review analyzed statements from 22 medical organizations in the United States to identify commonalities in the definition and governance of point-of-care ultrasound (POCUS). A total of 41 statements were included. The review found that the most commonly used elements in defining POCUS were "focused," "bedside," and "patient care." In terms of governance, consistent requirements included specific training programs, documentation in medical records, continuous quality assurance, and standards for credentialing and privileging. These findings suggest the existence of essential commonalities that could facilitate communication and the development of standardized POCUS programs in the future.


Asunto(s)
Sistemas de Atención de Punto , Pruebas en el Punto de Atención , Estados Unidos , Humanos , Ultrasonografía , Habilitación Profesional
10.
Allergy ; 77(2): 633-642, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34241919

RESUMEN

BACKGROUND: The aim of the BSP090 project is the establishment of European Pharmacopoeia Chemical Reference Substances (CRSs) in combination with corresponding standard ELISA methods for quantification of major allergens in allergen products. Here, we present data of a Phl p 5-specific sandwich ELISA that proved suitable for the quantification of Phl p 5, one of the major Timothy grass (Phleum pratense) pollen allergens. METHODS: A Phl p 5-specific ELISA system was assessed with respect to accuracy, precision, inter-assay (within laboratory) and inter-laboratory variations, in a ring trial including 14 laboratories in Europe and the USA. Model samples containing recombinant Phl p 5a CRS as well as native grass pollen extracts were analysed. Each participant was instructed to perform at least one preliminary assay to familiarise with the protocol, followed by three independent assays. RESULTS: The candidate standard ELISA proved suitable to quantify recombinant and native Phl p 5 with satisfactory precision (93% of results within ±30% acceptance range). Inter-assay variation (max. GCV 24%) and especially inter-laboratory variation (max. GCV 13%) showed conclusive results. When assessing accuracy by means of recovery of recombinant spikes from a grass pollen extract matrix, similarly satisfactory spike recovery results were observed for the two spikes with higher concentrations (all within ±30% acceptance range), whereas recovery of the lowest concentration spike was slightly poorer with mean results of six laboratories exceeding acceptance range. CONCLUSIONS: Based on the collaborative study results, the assessed Phl p 5-specific immunoassay is appropriate to be proposed as European Pharmacopoeia standard method.


Asunto(s)
Alérgenos , Polen , Alérgenos/química , Ensayo de Inmunoadsorción Enzimática , Humanos , Phleum/química , Proteínas de Plantas/química , Poaceae , Estándares de Referencia
11.
Paediatr Anaesth ; 32(9): 1047-1053, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35735131

RESUMEN

BACKGROUND: Fluid administration in children undergoing surgery requires precision, however, determining fluid responsiveness can be challenging. Ultrasound has been used widely in the emergency department and intensive care units as a noninvasive, bedside manner of determining volume status, but the intraoperative period presents unique challenges as often the chest and abdomen are inaccessible for ultrasound. We investigate whether carotid artery ultrasound, specifically carotid flow time, can be used to determine fluid responsiveness in children under general anesthesia. METHODS: Prospective observational study of 87 children ages 1-12 years who were scheduled for elective noncardiac surgery. Ultrasound of the carotid artery and heart was performed at three time points: (1) after inhalational induction of anesthesia with the subject spontaneously breathing, (2) during positive pressure ventilation through endotracheal tube or supraglottic airway with tidal volume set at 8 ml/kg with PEEP of 10 cmH2 O, and (3) after a 10 ml/kg fluid bolus. Carotid flow time and cardiac output were measured from saved images. RESULTS: Corrected carotid flow time (FTc) increased with initiation of positive pressure ventilation in both fluid responders and nonresponders (352.7 vs. 365.3 msec, p = .005 in fluid responders; 348.3 vs. 365.2 msec, p = .001 in nonresponders). FTc increased after fluid bolus in both responders and nonresponders (365.3 vs. 397.6 msec, p < .001 in fluid responders; 365.2 vs. 397.2 msec, p < .001 in nonresponders). However, baseline FTc during spontaneous ventilation or positive pressure ventilation prior to fluid bolus was not associated with fluid responsiveness. DISCUSSION: Flow time increases with initiation of positive pressure ventilation and after administration of a fluid bolus. FTc may serve as an indicator of fluid status but does not predict fluid responsiveness in children under general anesthesia.


Asunto(s)
Fluidoterapia , Hemodinámica , Anestesia General/métodos , Gasto Cardíaco , Arterias Carótidas/diagnóstico por imagen , Niño , Preescolar , Fluidoterapia/métodos , Humanos , Lactante , Estudios Prospectivos , Volumen Sistólico
12.
Arthroscopy ; 38(5): 1618-1626, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34715279

RESUMEN

PURPOSE: (1) To compare the total number and dollar amount of industry funding and National Institutes of Health (NIH) funding to academic orthopaedic sports medicine surgeons and (2) to examine the impact of academic influence on industry funding and NIH funding to academic orthopaedic sports medicine surgeons. METHODS: Academic orthopaedic sports medicine surgeons were identified using faculty web pages. Academic influence was approximated by a physician's Hirsch index (h index) and number of publications and obtained from the Scopus database. Total industry payments were acquired through the Open Payments Database, and NIH funding was determined from the NIH website. Statistical analysis was performed using Mann-Whitney U test and Spearman correlations with significance set at P < .05. RESULTS: Physicians who received industry research payments and NIH funding had a significantly higher mean h index and more mean total publications than physicians who did not receive industry research payments and NIH funding. There were no significant differences in h index (P = .374) or number of publications (P = .126) between surgeons receiving industry nonresearch funding and those who did not. h Index and number of publications were both weakly correlated with the amount of industry research and nonresearch funding. CONCLUSION: Although academic influence is associated with industry research funding and NIH funding, there is no association between measures of academic influence and total industry and industry nonresearch payments. Combined with the weak associations between academic influence and the amount of industry payments, academic influence does not appear to be a major determinant of industry funding to academic orthopaedic sports medicine surgeons. CLINICAL RELEVANCE: Surgeons should be cognizant of potential conflicts with industry, but the relationship between academic sports medicine surgeons and industry may be less subject to bias than previously believed.


Asunto(s)
Cirujanos Ortopédicos , Ortopedia , Medicina Deportiva , Cirujanos , Humanos , National Institutes of Health (U.S.) , Estados Unidos
13.
J Emerg Med ; 62(1): 72-82, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34521545

RESUMEN

BACKGROUND: Intussusception is a common pediatric emergency. The two types of intussusception are ileocolic intussusception (ICI) and small bowel-small bowel intussusception (SB-SBI), and neither are easily distinguished clinically. ICI requires radiology personnel and potentially surgical assistance for its reduction. SB-SBI is managed expectantly, as many resolve spontaneously. Differentiating between ICI and SB-SBI through point-of-care ultrasound (POCUS) requires an understanding of their salient features. Identification of the correct type of intussusception immediately assists decision making and patient disposition. OBJECTIVE OF THE REVIEW: Our objective was to provide guidance on POCUS technique for intussusception identification, and to review the ultrasound literature differentiating ICI from SB-SBI. METHODS: We systematically searched 3 separate databases and gray literature to identify articles that met our criteria and assessed them for final review. The final articles were graded for quality using The National Institutes of Health quality assessment tool for observational cohort and cross-sectional studies. RESULTS: A total of 858 articles were identified. Six articles were included in the final review. All studies were conducted in pediatric patients in different countries. Most were found to have a fair quality of evidence. The linear transducer is used when evaluating intussusception. Both ICI and SB-SBI are identified easily on POCUS, but they differ sonographically with respect to region within the abdomen, intussusception parameters, lymph nodes, and other salient features seen on real-time video. CONCLUSIONS: ICI and SB-SBI can be identified and differentiated using several sonographic features. POCUS is capable of expeditiously aiding the emergency physician's decision making and disposition when managing intussusception.


Asunto(s)
Intususcepción , Abdomen/patología , Niño , Estudios Transversales , Humanos , Intususcepción/complicaciones , Intususcepción/diagnóstico por imagen , Sistemas de Atención de Punto , Estudios Retrospectivos , Estados Unidos
14.
J Shoulder Elbow Surg ; 31(9): e436-e443, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35562035

RESUMEN

BACKGROUND: There exists anecdotal evidence that influential faculty members actively dissuade orthopedic surgery residents from pursuing a fellowship in shoulder and elbow due to a perceived lack of availability of jobs following graduation. The aims of the present study are to evaluate whether this perception is true by characterizing the early career opportunities and practice characteristics of recent graduates of shoulder and elbow fellowship programs through a survey of graduates of the past 5 years. METHODS: An anonymous 39-question survey was designed and approved by the leadership of the American Shoulder and Elbow Surgeons (ASES). The survey was distributed via electronic mail to the fellowship directors and coordinators of the 31 ASES-recognized shoulder and elbow fellowship programs. The fellowship directors and coordinators then sent the survey to the shoulder and elbow fellowship graduates of the last 5 years (2016-2020). Following a total of 4 emails, the survey closed after 8 weeks, and descriptive statistical analysis was performed. RESULTS: Seventy-six of 171 (44.4%) fellows responded. In total, 89.5% were very or somewhat satisfied with their fellowship experience, and 90.8% would pursue a shoulder and elbow fellowship again. Notably, 100% of shoulder and elbow fellowship graduates surveyed in the past 5 years have secured employment. The average number of total orthopedic and shoulder and elbow cases performed annually was 296.7 (SD 141.3) and 173.9 (SD 120.2), respectively. In addition, 62.7% and 89% of respondents were very or somewhat satisfied with the volume and surgical complexity of shoulder and elbow cases, respectively. For the fellows that believed their case experience to be inadequate, the most common reasons were competition from other practices (66.0%) and inadequate patient volume (59.6%). CONCLUSION: Recent graduates of the ASES-recognized shoulder and elbow fellowship programs demonstrate a high level of satisfaction with the fellowship and their subspeciality selection. The majority of fellows believed that completing a shoulder and elbow fellowship enhanced their job opportunities. Altogether, there are ample job opportunities and high satisfaction with the volume and complexity of cases as an early career shoulder and elbow surgeon.


Asunto(s)
Becas , Ortopedia , Educación de Postgrado en Medicina , Codo , Empleo , Humanos , Ortopedia/educación , Hombro , Encuestas y Cuestionarios , Estados Unidos
15.
Pediatr Emerg Care ; 38(2): e849-e855, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-35100784

RESUMEN

OBJECTIVES: Using an education and assessment tool, we examined the number of cases necessary to achieve a performance benchmark in image interpretation of pediatric soft tissue, cardiac, lung, and focused assessment with sonography for trauma (FAST) point-of-care ultrasound (POCUS) applications. We also determined interpretation difficulty scores to derive which cases provided the greatest diagnostic challenges. METHODS: Pediatric emergency physicians participated in web-based pediatric POCUS courses sponsored by their institution as a credentialing priority. Participants deliberately practiced cases until they achieved diagnostic interpretation scores of combined 90% accuracy, sensitivity, and specificity. RESULTS: Of the 463 who enrolled, 379 (81.9%) completed cases. The median (interquartile range) number of cases required to achieve the performance benchmark for soft tissue was 94 (68-128); cardiac, 128 (86-201); lung, 87 (25-118); and FAST, 93 (68-133) (P < 0001). Specifically, cases completed to achieve benchmark were higher for cardiac relative to other applications (P < 0.0001 for all comparisons). In soft tissue cases, a foreign body was more difficult to diagnose than cobblestoning and hypoechoic collections (P = 0.036). Poor cardiac function and abnormal ventricles were more difficult to interpret with accuracy than normal (P < 0.0001) or pericardial effusion cases (P = 0.01). The absence of lung sliding was significantly more difficult to interpret than normal lung cases (P = 0.028). The interpretation difficulty of various FAST imaging findings was not significantly different. CONCLUSIONS: There was a significant variation in number of cases required to reach a performance benchmark. We also identified the specific applications and imaging findings that demonstrated the greatest diagnostic challenges. These data may inform future credentialing guidelines and POCUS learning interventions.


Asunto(s)
Evaluación Enfocada con Ecografía para Trauma , Sistemas de Atención de Punto , Niño , Corazón , Humanos , Pruebas en el Punto de Atención , Ultrasonografía
16.
PLoS Comput Biol ; 16(9): e1008194, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32936799

RESUMEN

CRISPR screens are a powerful technology for the identification of genome sequences that affect cellular phenotypes such as gene expression, survival, and proliferation. By targeting non-coding sequences for perturbation, CRISPR screens have the potential to systematically discover novel functional sequences, however, a lack of purpose-built analysis tools limits the effectiveness of this approach. Here we describe RELICS, a Bayesian hierarchical model for the discovery of functional sequences from CRISPR screens. RELICS specifically addresses many of the challenges of non-coding CRISPR screens such as the unknown locations of functional sequences, overdispersion in the observed single guide RNA counts, and the need to combine information across multiple pools in an experiment. RELICS outperforms existing methods with higher precision, higher recall, and finer-resolution predictions on simulated datasets. We apply RELICS to published CRISPR interference and CRISPR activation screens to predict and experimentally validate novel regulatory sequences that are missed by other analysis methods. In summary, RELICS is a powerful new analysis method for CRISPR screens that enables the discovery of functional sequences with unprecedented resolution and accuracy.


Asunto(s)
Sistemas CRISPR-Cas/genética , Genómica/métodos , Análisis de Secuencia de ADN/métodos , Programas Informáticos , Teorema de Bayes , Humanos , Células Jurkat , ARN Guía de Kinetoplastida/genética
17.
Pediatr Radiol ; 51(12): 2253-2269, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33978795

RESUMEN

Trauma is the leading cause of morbidity and mortality in children, and rapid identification of organ injury is essential for successful treatment. Contrast-enhanced ultrasound (CEUS) is an appealing alternative to contrast-enhanced CT in the evaluation of children with blunt abdominal trauma, mainly with respect to the potential reduction of population-level exposure to ionizing radiation. This is particularly important in children, who are more vulnerable to the hazards of ionizing radiation than adults. CEUS is useful in hemodynamically stable children with isolated blunt low- to moderate-energy abdominal trauma to rule out solid organ injuries. It can also be used to further evaluate uncertain contrast-enhanced CT findings, as well as in the follow-up of conservatively managed traumatic injuries. CEUS can be used to detect abnormalities that are not apparent by conventional US, including infarcts, pseudoaneurysms and active bleeding. In this article we present the current experience from the use of CEUS for the evaluation of pediatric blunt abdominal trauma, emphasizing the examination technique and interpretation of major abnormalities associated with injuries in the liver, spleen, kidneys, adrenal glands, pancreas and testes. We also discuss the limitations of the technique and offer a review of the major literature on this topic in children, including an extrapolation of experience from adults.


Asunto(s)
Traumatismos Abdominales , Heridas no Penetrantes , Traumatismos Abdominales/diagnóstico por imagen , Adulto , Niño , Medios de Contraste , Humanos , Bazo/diagnóstico por imagen , Ultrasonografía , Heridas no Penetrantes/diagnóstico por imagen
18.
J Arthroplasty ; 36(8): 3004-3009, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33812708

RESUMEN

BACKGROUND: The relationship between industry payments and academic influence, as measured by the Hirsch index (h-index) and number of publications, among adult reconstruction surgeons is not well characterized. The aims of the present study are to determine the relationship between an adult reconstruction surgeons' academic influence and their relevant industry payments and National Institutes of Health (NIH) funding. METHODS: Adult reconstruction surgeons were identified through the websites for the orthopedic surgery residency programs in the United States during the 2019-2020 academic year. Academic influence was approximated by each physician's h-index and total number of publications. Industry payment data were obtained through the Open Payments Database, and NIH funding was determined through the NIH website. Mann-Whitney U testing and Spearman correlations were performed to examine relevant associations. RESULTS: Surgeons who received industry research payments had a higher mean h-index (16.1 vs 10.2, P < .001) and mean number of publications (79.1 vs 35.9, P < .001) than physicians who received no industry research payments. Surgeons receiving NIH funding had a higher mean h-index (48.1 vs 10.4, P < .001) and mean number of publications (294.5 vs 36.8, P < .001) than surgeons who did not receive NIH funding. There was no association between the average h-index (P = .668) and number of publications (P = .387) among adult reconstruction surgeons receiving industry nonresearch funding. CONCLUSION: h-index and total publications do not seem to be associated with industry nonresearch payments in the field of total joint arthroplasty. Altogether, these data suggest that industry bias may not play a strong role in total joint arthroplasty.


Asunto(s)
Industrias , Cirujanos , Adulto , Artroplastia , Humanos , Estados Unidos
19.
J Arthroplasty ; 36(7S): S258-S263.e1, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33162278

RESUMEN

BACKGROUND: A higher volume of primary total hip arthroplasty (THA) is starting to be performed as an outpatient procedure. However, data on appropriate patient selection for this surgical protocol is scarce. METHODS: Patients who underwent primary THA were identified in the 2012-2018 National Surgical Quality Improvement Program database. Outpatient procedure was defined as having a hospital length of stay of 0 days. The primary outcome was a readmission within the 30-day postoperative period. Risk factors for and effect of overnight hospital stay on 30-day readmission after outpatient THA were identified through multivariable models. Reasons for and timing of readmission were also identified. RESULTS: A total of 5245 outpatient THA patients and 44,171 patients who stayed 1 night were identified. The incidence of 30-day readmission after outpatient THA was 1.60% (95% confidence interval [CI] 1.26-1.94). Risk factors for 30-day readmission after outpatient THA include the following: older age relative to 18-60 years old (most notably 71-75 years old, relative risk [RR] = 2.3, 95% CI = 1.15-4.62; 76-80 years old, RR = 6.6, 95% CI = 3.55-12.43; and >80 years old, RR = 5.6, 95% CI = 2.43-12.89, P < .001) and bleeding disorders (RR = 4.5, 95% CI = 1.45-14.31, P = .010). For patients who had some of these risk factors, their risk of medically related 30-day readmission was reduced if they had stayed 1 night at the hospital (P < .05). The majority of readmissions were surgically related (62%), including wound complications (27%) and periprosthetic fractures (25%). CONCLUSION: The rate of 30-day readmission after outpatient THA was low. Patients who are at high risk for 30-day readmission after outpatient THA include those with older age and bleeding disorders. Some of these patients may benefit from an inpatient hospital stay.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Readmisión del Paciente , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/efectos adversos , Humanos , Tiempo de Internación , Pacientes Ambulatorios , Alta del Paciente , Complicaciones Posoperatorias/epidemiología , Factores de Riesgo
20.
J Arthroplasty ; 36(5): 1719-1728, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33248920

RESUMEN

BACKGROUND: Preoperative anemia is an important risk factor for developing complications following revision hip (rTHA) and knee (rTKA) arthroplasty. We aim to determine the effect of anemia severity on 30-day postoperative complications following revision hip and knee arthroplasty. METHODS: A retrospective cohort study was conducted using the American College of Surgeons National Quality Improvement Program Database. All patients who underwent revision joint arthroplasty (rTJA) between 2006 to 2017 were identified and grouped based upon the hematocrit (Hct) level. Anemia was defined as Hct <36% for women and <39% for men, and further stratified into mild anemia (Hct 33% to 36% for women, Hct 33% to 39% for men), and moderate to severe anemia (Hct <33% for both men and women). Univariate and multivariate analysis were used to evaluate the incidence of multiple adverse events within 30 days after TJA. RESULTS: A total of 8932 patients undergoing rTHA and 13,313 patients undergoing rTKA were included for analysis. On multivariate adjustment, patients undergoing rTHA with moderate to severe anemia had an increased odds of 5.437 (95% Confidence Interval (CI) 4.604 to 6.421; P < .001) of developing any postoperative complication. On multivariate adjustment, patients undergoing rTKA with moderate to severe anemia had increased odds of 6.731 (95% Confidence Interval (CI) 5.540 to 8.179; P < .001) of developing any postoperative complication. CONCLUSION: The increasing severity of anemia was associated with an increasing risk of developing any postoperative complication and death following revision hip and knee arthroplasty. There is a significant trend between diminishing preoperative hematocrit levels and increasing odds of postoperative complication.


Asunto(s)
Anemia , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Anemia/epidemiología , Anemia/etiología , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Femenino , Humanos , Masculino , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Reoperación , Estudios Retrospectivos , Factores de Riesgo
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