RESUMEN
BACKGROUND: The concept of delayed skeletal maturity in Legg-Calve-Perthes Disease (LCPD) has been well identified with the Greulich and Pyle (GP) atlas showing 1 to 2 years delay. Recently the optimized Oxford hip skeletal age (Optimized Oxford) system has been developed and shown to have similar accuracy as the GP atlas for assessing skeletal maturity. However, this system has not been used to assess skeletal maturity in LCPD. METHODS: A retrospective review of a prospective, multicenter study of patients with LCPD treated from 1984 to 1991 and followed to skeletal maturity was performed. We identified all patients who had a left-hand radiograph at the time of presentation with an accompanying anteroposterior pelvis radiograph including the contralateral hip. Patients were excluded if their age at presentation fell outside the validated range for the Optimized Oxford system. GP atlas was used to determine bone age using left-hand radiographs and the nonaffected hip radiographs were used to calculate the Optimized Oxford bone age. Skeletal maturity indices were compared with chronological age (CA) to determine the discrepancy between methodologies. RESULTS: A total of 71 patients met inclusion criteria (mean 9.5 ± 1.2 y at presentation, 42.2% females). The mean GP bone age was 1.4 years younger than CA (95% CI: 1.01-1.76 y), with the discrepancy being greater for boys than girls (1.8 vs 0.86 y, P = 0.02). The mean Optimized Oxford bone age was 0.31 years older than CA (95% CI: 0.24-0.38 y) and correlated significantly with CA ( R = 0.97, P < 0.001). There were no sex differences in the Optimized Oxford bone age relative to CA ( P = 0.32). The GP bone age was a mean of 1.7 years younger than the Optimized Oxford bone age (95% CI: 1.35-2.05 y). CONCLUSION: Skeletal maturity assessment in children with LCPD varies according to the utilized maturity system. The Optimized Oxford bone age more closely mirrors the patient's CA and does not correlate with the GP bone age, which reveals a delayed maturation.
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Enfermedad de Legg-Calve-Perthes , Niño , Masculino , Femenino , Humanos , Lactante , Enfermedad de Legg-Calve-Perthes/diagnóstico por imagen , Enfermedad de Legg-Calve-Perthes/complicaciones , Estudios Prospectivos , Estudios Retrospectivos , Radiografía , Determinación de la Edad por el EsqueletoRESUMEN
STUDY QUESTION: What are children's perspectives of the quality of their relationships with their parents and their own psychological well-being in families created using egg donation? SUMMARY ANSWER: Children's scores indicated good parent-child relationship quality and high levels of psychological well-being, with children in families created using egg donation rating their relationships with their mothers as higher in warmth/enjoyment than children in a comparison group of families created using IVF. WHAT IS KNOWN ALREADY: Little is known about how children in families created through egg donation view their family relationships and their own psychological well-being. Research with 7-and-10-year-olds in anonymous egg donation families has indicated good parent-child relationship quality from children's perspectives, but studies have not involved younger children or those conceived following identity-release egg donation. STUDY DESIGN, SIZE, DURATION: This study included 50 children who had been born through egg donation and a comparison group of 43 children conceived through IVF with the parents' own gametes. Data were collected between April 2018 and December 2019. The sample forms part of a larger longitudinal study examining family functioning in families created through fertility treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: Children were aged 5 years old and had been born into families with different-sex couple parents. All families were visited at home. Children were administered the Berkeley Puppet Interview, a standardized assessment of parent-child relationship quality and psychological well-being. MAIN RESULTS AND THE ROLE OF CHANCE: Children in egg donation families rated their relationships with their mothers as higher in warmth and enjoyment than did children in IVF families. No differences were found between the two family types in children's ratings of the father-child relationship, or in children's ratings of their own psychological well-being. LIMITATIONS, REASONS FOR CAUTION: It is possible that children who did not consent to take part in the research had less positive perceptions of their family and themselves than children who participated. WIDER IMPLICATIONS OF THE FINDINGS: The findings are relevant to UK clinics offering identity-release egg donation, to parents who have used egg donation to create their family and to individuals and couples considering their fertility treatment options. That children in egg donation families were more similar than different to children in IVF families in their self-concept and perception of their family relationships should prove reassuring. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by a Wellcome Trust Collaborative Award [208013/Z/17]. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.
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Ajuste Emocional , Relaciones Padres-Hijo , Adaptación Psicológica , Preescolar , Femenino , Humanos , Estudios Longitudinales , Padres/psicologíaRESUMEN
BACKGROUND: Femoral neck stress fractures are a common condition affecting military service members, most noticeably during basic combat training. Previous studies have investigated the risk factors for femoral neck stress fracture development in basic trainees and outcomes associated with treatment; however, few studies have focused on operatively treated femoral neck stress fracture in the military trainee. Doing so would be important not only for the military, but also providers caring for athletes, such as distance runners, who have a heightened risk for femoral neck stress fracture development. QUESTIONS/PURPOSES: (1) What proportion of US Army trainees completing basic combat training at Fort Jackson, SC, USA, who undergo surgery for femoral neck stress fracture during basic training subsequently leave military service because of the injury? (2) What factors are related to the patient or the fracture are associated with a higher likelihood of military separation? (3) What factors on the initial MRI are associated with progression of the stress fracture extent? METHODS: A retrospective study of a longitudinally maintained database of stress injuries involving basic combat trainees from a single military post was reviewed over a 3-year period. Inclusion criteria included basic trainees undergoing surgery for a femoral neck stress fracture between January 2018 and June 2020 with a minimum of 1-year follow-up. Surgery was indicated for service members with complete and tension-sided femoral neck stress fractures and those with high risk compression-sided stress fractures, generally representing fractures involving more than 50% of the femoral neck width. Over the study period, 57 service members (51% [29 of 57] women with a mean age of 24 years) underwent surgery for a femoral neck stress fracture, and all 57 had a minimum of 1-year follow-up. Identified service members underwent independent data collection including injury and radiographic parameters based on chart and imaging review. Documented fracture line progression on repeat imaging was present in 39% of service members, with a mean fracture line progression of 55% of the femoral neck width. Service members were subdivided based upon the ability to return to military service at 1 year. Univariate analysis was performed using patient and injury variables to identify factors associated with the ability to return to military service. RESULTS: Overall, 58% (33 of 57) of service members who had a femoral neck stress fracture treated surgically underwent military separation. A higher proportion of service members who demonstrated fracture line progression leading to surgical treatment remained in the military (58% [14 of 24] versus 30% [10 of 33]; odds ratio 0.3 [95% confidence interval (CI) 0.1 to 0.9]; p = 0.03). With the numbers available, we found no other patient- or fracture-related variables associated with military separation, although we suspect we may have been underpowered on some of these comparisons, in particular gender (61% [20 of 33] of individuals separated after surgery for this injury were women compared with 38% [9 of 24] who were retained; OR 2.6 [95% CI 0.9 to 7.56]; p = 0.09). The extent of osseous edema on T1-weighted imaging in association with a hip effusion demonstrated a significant positive correlation with final fracture percentage (r = 0.62; p = 0.003). CONCLUSION: Military service members with a femoral neck stress fracture initially managed nonoperatively but with progression of the fracture line requiring surgical intervention were more likely to return to military duties and complete basic combat training, suggesting that early diagnosis of femoral neck stress fractures may be associated with better functional recovery after surgical treatment. Additionally, the extent of the osseous edema on initial MRI T1-weighted imaging sequences may help predict the final extent of femoral neck stress fractures on repeat imaging. Further investigations should incorporate patient-reported outcomes and further explore factors associated with fracture progression and the inability to return to active duty or sport. LEVEL OF EVIDENCE: Level III, therapeutic study.
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Fracturas del Cuello Femoral , Fracturas por Estrés , Personal Militar , Adulto , Edema , Femenino , Fracturas del Cuello Femoral/diagnóstico por imagen , Fracturas del Cuello Femoral/cirugía , Cuello Femoral/diagnóstico por imagen , Cuello Femoral/cirugía , Fracturas por Estrés/diagnóstico por imagen , Fracturas por Estrés/etiología , Fracturas por Estrés/cirugía , Humanos , Masculino , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Orthopaedic cast saws are an integral component to a pediatric orthopaedic practice but can also be associated with patient anxiety and noise exposure for patient. Although previous studies have deemed the noise generation from orthopaedic cast saws to be within safe occupational exposure levels, no study to date has compared the noise generation from a cast saw used in various exam room settings. METHODS: A simulated fiberglass cast model was used. Noise generation was assessed using calibrated sound level meters with measurements performed at 18 inches, 36 inches, and 6 ft measured from the cast saw. Measurements were performed in 1 of 2 clinical settings: (1) an open bay setting and (2) an enclosed exam room. In the enclosed exam room, the 6-foot measurement was performed behind the closed exam door. An orthopaedic cast saw with built-in vacuum was used to continuously cut the fiberglass model for 1 minute with measurements of peak and mean sound generation, recorded in decibels (dB), a logarithmic scale. Three measurements were recorded at each distance. Between group comparisons were performed with statistical significance set at P=0.05. RESULTS: Baseline sound levels were similar between cohorts with progressive decreases in mean sound with increasing distance from the saw. Mean sound levels were significantly higher in the enclosed room setting at 18 inches (92.8 dB, 95% confidence interval (CI): 91.72-93.88 vs. 90.6 dB, 95% CI: 89.91-91.29; P=0.043] and 36 inches (90.3 dB, 95% CI: 89.9-90.7 vs. 86.0 dB, 95% CI: 85.18-86.82; P=0.017). At 6-ft distance, however, the enclosed room demonstrated a 13.8-fold sound reduction compared with the open bay (72.0 dB, 95% CI: 71.59-72.4 vs. 83.4 dB, 83.14-83.72; P<0.001). CONCLUSION: By closing the exam door, a 13-fold reduction in noise exposure can be achieved for adjacent patients and personnel. Consideration should be given for using orthopaedic cast saws in an enclosed exam room to prevent unnecessary noise exposure with hearing protection of cast saw operators and treated patients. CLINICAL RELEVANCE: Orthopaedic cast removal.
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Ruido en el Ambiente de Trabajo , Exposición Profesional , Ortopedia , Niño , HumanosRESUMEN
PURPOSE: To assess the accuracy of measuring glenoid version on magnetic resonance imaging (MRI) in the presence of varying amounts of the medial scapula body as compared with the gold standard of glenoid version measured on computed tomography (CT) imaging, including the entire scapula in a cohort of young patients with shoulder instability and without glenohumeral arthritis. METHODS: A retrospective review was performed on instability patients with preoperative MRI and CT imaging. Measurements of available scapular width and glenoid version were performed using the Cobb angle method to measure the angle between the plane of the glenoid fossa to Friedman's line on axial images. Intra- and interrater reliability analysis was performed using intraclass correlation coefficients to assess agreement between MRI and CT measurements. Paired t tests were used to compare measurement differences between MRI and CT. RESULTS: Thirty-two patients with both MRI and CT scans were assessed. Intra- and inter-rater assessment revealed strong agreement for scapular width measurement. For glenoid version measurement, intra-rater agreement was excellent and inter-rater agreement was moderate on CT and good on MRI. The mean available scapular body width was 24.7 mm longer on CT as compared with MRI (95% confidence interval 17.5-31.9, P < .0001; 109.8 ± 8.2 mm vs 85.1 ± 16.9 mm, respectively), with MRI having an average of 78.2% (±17.6%) of the CT scapular width shown on CT. No significant difference in glenoid version was found between MRI and CT (95% confidence interval -0.87 to 1.75, P = .499; MRI -2.57° vs CT -2.13°). CONCLUSION: MRI provided significantly shorter available scapular widths when compared with CT imaging in a cohort of patients with glenohumeral instability and without arthritis. However, this failed to produce a significant difference of ≥5° in measured glenoid version compared with CT measurements when 75% (8 cm) of the scapular width was present on MRI. Measuring glenoid version on MRI does not appear to be significantly affected when the entirety of the medial border of the scapula is not included in the imaging field. LEVEL OF EVIDENCE: Level III; study of diagnostic test.
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Inestabilidad de la Articulación/diagnóstico , Imagen por Resonancia Magnética/métodos , Procedimientos Ortopédicos/métodos , Escápula/diagnóstico por imagen , Articulación del Hombro/cirugía , Tomografía Computarizada por Rayos X/métodos , Humanos , Inestabilidad de la Articulación/cirugía , Reproducibilidad de los Resultados , Estudios Retrospectivos , Articulación del Hombro/diagnóstico por imagenRESUMEN
Back pain and spinal deformity in the pediatric and adolescent patient population are common reasons for presentation to the orthopaedic surgeon, and although most conditions are benign and self-limiting, a standardized approach to the history and physical examination can identify concerning signs and symptoms as well as aid in determining the final diagnosis and a recommended treatment plan. The most common and concerning etiologies of back pain and spinal deformity will be reviewed, along with nonsurgical and surgical management of these conditions.
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Examen Físico , Enfermedades de la Columna Vertebral , Columna Vertebral , Adolescente , Niño , HumanosRESUMEN
PURPOSE: To evaluate whether characteristics such as age, height, weight, sex, or body mass index affected the distal tibial dimensions and radius of curvature (ROC) of a potential donor for anterior glenoid augmentation. METHODS: A retrospective review of magnetic resonance imaging of ankles without bony trauma was performed, and the anteroposterior (AP) and medial-lateral (ML) distances and ROC of the tibial plafond articular surface were measured. Demographic characteristics, including age, sex, height, weight, and body mass index, were recorded. RESULTS: A total of 141 imaging studies were included (73 men and 68 women; average age, 38.2 ± 12.65 years). All potential specimens accommodated harvest of a 10 × 22-mm distal tibial allograft bone block. Men had greater ML (42.74 cm [95% confidence interval (CI), 42.09-43.39 cm] vs 38.01 cm [95% CI, 37.30-38.72 cm]; P < .001) and AP (38.16 cm [95% CI, 37.47-38.85 cm] vs 34.57 cm [95% CI, 33.97-35.17 cm]; P < .001) dimensions. Significant moderately positive correlations were found for AP dimensions with height (r = 0.584, P < .001) and weight (r = 0.383, P < .001) and for ML dimensions with height (r = 0.711, P < .001) and weight (r = 0.467, P < .001). ROC was positively correlated with height (r = 0.509, P < .001) and weight (r = 0.294, P < .001). Patient age was not related to either the AP or ML distal tibial dimensions or ROC. CONCLUSIONS: After magnetic resonance imaging analysis, all potential donors permitted harvest of a standard-sized distal tibial allograft irrespective of sex or common anthropometric measures, and 85.8% showed distal tibial morphology acceptable for glenoid augmentation. AP and ML graft dimensions and ROC correlated significantly with height and weight. LEVEL OF EVIDENCE: Level II, diagnostic study.
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Trasplante Óseo/métodos , Articulación del Hombro/cirugía , Tibia/cirugía , Adolescente , Adulto , Anciano , Aloinjertos , Estatura , Índice de Masa Corporal , Peso Corporal , Trasplante Óseo/normas , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Ortopedia/normas , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/cirugía , Estudios Retrospectivos , Articulación del Hombro/diagnóstico por imagen , Tibia/diagnóstico por imagen , Trasplante Homólogo/métodos , Trasplante Homólogo/normas , Adulto JovenRESUMEN
Background: Activation of the phosphoinisitide-3 kinase (PI3K) pathway through mutation and constitutive upregulation has been described in renal cell carcinoma (RCC), making it an attractive target for therapeutic intervention. We performed a randomized phase II study in vascular endothelial growth factor (VEGF) therapy refractory patients to determine whether MK-2206, an allosteric inhibitor of AKT, was more efficacious than the mammalian target of rapamycin inhibitor everolimus. Patients and methods: A total of 43 patients were randomized in a 2:1 distribution, with 29 patients assigned to the MK-2206 arm and 14 to the everolimus arm. Progression-free survival (PFS) was the primary endpoint. Results: The trial was closed at the first futility analysis with an observed PFS of 3.68 months in the MK-2206 arm and 5.98 months in the everolimus arm. Dichotomous response rate profiles were seen in the MK-2206 arm with one complete response and three partial responses in the MK-2206 arm versus none in the everolimus arm. On the other hand, progressive disease was best response in 44.8% of MK2206 versus 14.3% of everolimus-treated patients. MK-2206 induced significantly more rash and pruritis than everolimus, and dose reduction occurred in 37.9% of MK-2206 versus 21.4% of everolimus-treated patients. Genomic analysis revealed that 57.1% of the patients in the PD group had either deleterious TP53 mutations or ATM mutations or deletions. In contrast, none of the patients in the non-PD group had TP53 or ATM defects. No predictive marker for response was observed in this small dataset. Conclusions: Dichotomous outcomes are observed when VEGF therapy refractory patients are treated with MK-2206, and MK-2206 does not demonstrate superiority to everolimus. Additionally, mutations in DNA repair genes are associated with early disease progression, indicating that dysregulation of DNA repair is associated with a more aggressive tumor phenotype in RCC.
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Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Everolimus/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Renales/mortalidad , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate mifepristone as an adjunct to, or replacement for, osmotic dilators for cervical preparation in surgical abortion after 19 weeks of gestation. DESIGN: Site-stratified, double-blinded randomised controlled trial. SETTING: Two tertiary care teaching hospitals. POPULATION: Women undergoing dilation and evacuation at 19-236/7 weeks of gestation from November 2013 through November 2015. METHODS: Participants were randomised to receive (1) mifepristone alone (n = 27), (2) osmotic dilators with mifepristone (n = 27) or (3) osmotic dilators with placebo (n = 21) with all receiving pre-procedure misoprostol. MAIN OUTCOME MEASURES: Operative time, preoperative cervical dilation and complications. RESULTS: We enrolled 75 participants; mean gestation 21 weeks. Pre-procedure cervical dilation was ≥3 cm in 4, 52, and 57% of participants in groups 1, 2, and 3, respectively (P < 0.005). Mifepristone with misoprostol for cervical preparation resulted in longer procedure times compared with osmotic dilators, with median total procedure times of (1) 18.5 (8-52), (2) 12 (7-25), and (3) 13 (6-26) minutes (P ≤ 0.005). Excluding time required for manual dilation, procedure times were similar: median times from dilation complete to evacuation complete were (1) 10.5 (4-23), (2) 8.5 (5-24), and (3) 10 (4-20) minutes (P = 0.10). Complications occurred in seven cases, six with trainees and one with an attending physician (P = 0.03), with difference by study group not reaching statistical significance (P = 0.12). CONCLUSIONS: Elimination of osmotic dilators has the potential to decrease burden and opportunity cost of cervical preparation. The longer procedure time, related to manual dilation, is offset by decreasing dilator-related preoperative time and discomfort. Provider experience may impact risk when eliminating dilators. TWEETABLE ABSTRACT: Mifepristone and misoprostol for cervical preparation prior to D&E has potential to reduce barriers to care.
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Abortivos no Esteroideos/administración & dosificación , Aborto Inducido , Cuello del Útero/efectos de los fármacos , Mifepristona/administración & dosificación , Misoprostol/administración & dosificación , Aborto Inducido/métodos , Adulto , Cuello del Útero/fisiología , Terapia Combinada , Dilatación , Método Doble Ciego , Femenino , Humanos , Embarazo , Segundo Trimestre del Embarazo , Resultado del TratamientoRESUMEN
BACKGROUND: Circumferential casting is a vital component of nonoperative fracture management. These casts are commonly valved to release pressure and decrease the risk of complications from swelling. However, little information exists regarding the effect of different casting supplies on the pressure within the cast. METHODS: Seventy-five long-arm casts were performed on human volunteers, divided between 5 experimental groups with 15 casts in each groups. Testing groups consisted of 2 groups with a plaster short-arm cast overwrapped with fiberglass to a long arm with either cotton or synthetic cast padding. The 3 remaining groups included fiberglass long-arm casts with cotton, synthetic, or waterproof cast padding. A pediatric blood pressure cuff bladder was placed within the cast and inflated to 100 mm Hg. After inflation, the cast was sequentially released with pressure reading preformed after each stage. Order of release consisted of cast bivalve, cast padding release, and cotton stockinet release. After release, the cast was overwrapped with a loose elastic bandage. Difference in pressure readings were compared based upon the cast material. RESULTS: Pressures within the cast were found to decrease with sequential release of cast. The cast type had no effect of change in pressure. Post hoc testing demonstrated that the type of cast padding significantly affected the cast pressures with waterproof padding demonstrating the highest pressure readings at all time-points in the study, followed by synthetic padding. Cotton padding had the lowest pressure readings at all time-points. DISCUSSION: Type of cast padding significantly influences the amount of pressure within a long-arm cast, even after bivalving the cast and cutting the cast padding. Cotton cast padding allows for the greatest change in pressure. CLINICAL RELEVANCE: Cotton padding demonstrates the greatest change in pressure within a long-arm cast after undergoing bivalve. Synthetic and waterproof cast padding should not be used in the setting of an acute fracture to accommodate swelling.
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Moldes Quirúrgicos , Inmovilización/instrumentación , Presión , Sulfato de Calcio , Fibra de Algodón , Vidrio , Voluntarios Sanos , Humanos , Inmovilización/métodos , Poliésteres , Tereftalatos Polietilenos , PoliuretanosRESUMEN
Anterior knee pain is a common complaint among military members, with a negative impact on operational readiness. A tibial tubercle osteotomy is one treatment option for select etiologies of anterior knee pain and has been reported to result in high rates of return to activity. A retrospective review of active duty service members undergoing a tibial tubercle osteotomy at a single army medical center was performed. Thirteen active duty service members were identified as undergoing a tibial tubercle osteotomy. Nine patients remained on active duty at 1 year following surgery. After 24 months, only four service members remained on active duty, while seven were medically retired. Seventy-five percent of patients who underwent concomitant cartilaginous procedure underwent a medical discharge. A small subset of active duty military personnel who underwent a tibial tubercle osteotomy was able to remain on active duty, but concomitant cartilaginous procedures did not appear to be compatible with retention on active duty because of the high physical demands placed on soldiers. (Journal of Surgical Orthopaedic Advances 26(4):262-265, 2017).
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Artralgia/cirugía , Articulación de la Rodilla , Personal Militar , Osteotomía/métodos , Reinserción al Trabajo , Tibia/cirugía , Adulto , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: Incorporation of multiple enrichment biomarkers into prospective clinical trials is an active area of investigation, but the factors that determine clinical trial enrollment following a molecular prescreening program have not been assessed. PATIENTS AND METHODS: Patients with 5-fluorouracil-refractory metastatic colorectal cancer at the MD Anderson Cancer Center were offered screening in the Assessment of Targeted Therapies Against Colorectal Cancer (ATTACC) program to identify eligibility for companion phase I or II clinical trials with a therapy targeted to an aberration detected in the patient, based on testing by immunohistochemistry, targeted gene sequencing panels, and CpG island methylation phenotype assays. RESULTS: Between August 2010 and December 2013, 484 patients were enrolled, 458 (95%) had a biomarker result, and 157 (32%) were enrolled on a clinical trial (92 on biomarker-selected and 65 on nonbiomarker selected). Of the 458 patients with a biomarker result, enrollment on biomarker-selected clinical trials was ninefold higher for predefined ATTACC-companion clinical trials as opposed to nonpredefined biomarker-selected clinical trials, 17.9% versus 2%, P < 0.001. Factors that correlated positively with trial enrollment in multivariate analysis were higher performance status, older age, lack of standard of care therapy, established patient at MD Anderson, and the presence of an eligible biomarker for an ATTACC-companion study. Early molecular screening did result in a higher rate of patients with remaining standard of care therapy enrolling on ATTACC-companion clinical trials, 45.1%, in contrast to nonpredefined clinical trials, 22.7%; odds ratio 3.1, P = 0.002. CONCLUSIONS: Though early molecular prescreening for predefined clinical trials resulted in an increase rate of trial enrollment of nonrefractory patients, the majority of patients enrolled on clinical trials were refractory to standard of care therapy. Within molecular prescreening programs, tailoring screening for preidentified and open clinical trials, temporally linking screening to treatment and optimizing both patient and physician engagement are efforts likely to improve enrollment on biomarker-selected clinical trials. CLINICAL TRIALS NUMBER: The study NCT number is NCT01196130.
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Biomarcadores de Tumor/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Metilación de ADN/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Islas de CpG/genética , Determinación de la Elegibilidad , Femenino , Fluorouracilo/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Estadificación de Neoplasias , Selección de PacienteRESUMEN
BACKGROUND: Next-generation sequencing in cancer research may reveal germline variants of clinical significance. We report patient preferences for return of results and the prevalence of incidental pathogenic germline variants (PGVs). PATIENTS AND METHODS: Targeted exome sequencing of 202 genes was carried out in 1000 advanced cancers using tumor and normal DNA in a research laboratory. Pathogenic variants in 18 genes, recommended for return by The American College of Medical Genetics and Genomics, as well as PALB2, were considered actionable. Patient preferences of return of incidental germline results were collected. Return of results was initiated with genetic counseling and repeat CLIA testing. RESULTS: Of the 1000 patients who underwent sequencing, 43 had likely PGVs: APC (1), BRCA1 (11), BRCA2 (10), TP53 (10), MSH2 (1), MSH6 (4), PALB2 (2), PTEN (2), TSC2 (1), and RB1 (1). Twenty (47%) of 43 variants were previously known based on clinical genetic testing. Of the 1167 patients who consented for a germline testing protocol, 1157 (99%) desired to be informed of incidental results. Twenty-three previously unrecognized mutations identified in the research environment were confirmed with an orthogonal CLIA platform. All patients approached decided to proceed with formal genetic counseling; in all cases where formal genetic testing was carried out, the germline variant of concern validated with clinical genetic testing. CONCLUSIONS: In this series, 2.3% patients had previously unrecognized pathogenic germline mutations in 19 cancer-related genes. Thus, genomic sequencing must be accompanied by a plan for return of germline results, in partnership with genetic counseling.
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Mutación de Línea Germinal/genética , Proteínas de Neoplasias/genética , Neoplasias/genética , Exoma/genética , Asesoramiento Genético , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Neoplasias/diagnóstico , Neoplasias/patologíaRESUMEN
Donor-derived tuberculosis (TB) is an increasingly recognized complication of solid organ transplantation. We report a case of isoniazid-resistant pulmonary TB in a lung transplant recipient. The patient acquired the infection from the lung donor who was previously empirically treated with isoniazid for latent TB. The case highlights the caveat that, while adequate treatment of latent TB with isoniazid is presumed, meticulous screening of donors is required.
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Aloinjertos/microbiología , Antibacterianos/uso terapéutico , Antituberculosos/uso terapéutico , Fibrosis Quística/cirugía , Farmacorresistencia Bacteriana , Isoniazida/uso terapéutico , Tuberculosis Latente/tratamiento farmacológico , Trasplante de Pulmón/efectos adversos , Mycobacterium tuberculosis/fisiología , Tuberculosis Pulmonar/etiología , Adulto , Antibacterianos/administración & dosificación , Profilaxis Antibiótica , Antituberculosos/administración & dosificación , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Líquido del Lavado Bronquioalveolar , Broncoscopía , Fibrosis Quística/genética , Femenino , Fluoroquinolonas/administración & dosificación , Fluoroquinolonas/uso terapéutico , Humanos , Terapia de Inmunosupresión/efectos adversos , Isoniazida/administración & dosificación , Pruebas de Sensibilidad Microbiana , Moxifloxacino , Mycobacterium tuberculosis/aislamiento & purificación , Pseudomonas aeruginosa/aislamiento & purificación , Rifampin/administración & dosificación , Rifampin/uso terapéutico , Donantes de Tejidos , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiologíaRESUMEN
BACKGROUND: Jamaica, along with the Americas, experienced major epidemics of arboviral diseases transmitted by the Aedes aegypti mosquito in recent years. These include dengue fever in 2012, Chikungunya fever in 2014 and Zika virus infection (ZIKV) in 2016. We present the emergence of the ZIKV epidemic in Jamaica and outline the national response. METHODS: The Ministry of Health's preparedness included: heightened surveillance, clinical management guidance, vector control and management, laboratory capacity strengthening, training and staffing, risk communication and public education, social mobilization, inter-sectoral collaboration, resource mobilization and international cooperation. RESULTS: The first case of ZIKV was confirmed on January 29, 2016 with date of onset of January 17, 2016. From January 3 to July 30, 2016 (Epidemiological Week (EW) 1-30), 4648 cases of ZIKV were recorded (4576 suspected, 72 laboratory-confirmed). Leading symptoms were similar among suspected and confirmed cases: rash (71% and 88%), fever (65% and 53%) and joint pains (47% and 38%). There were 17 suspected cases of Guillain Barre syndrome; 383 were reported in pregnant women, with no reports of microcephaly to date. Zika and dengue viruses were circulating predominantly in 2016. At EW30, 1744 cases of dengue were recorded (1661 suspected and 83 confirmed). Dengue serotypes 3 and 4 were circulating with 121 reports of dengue haemorrhagic fever. CONCLUSION: The possibility exists for endemicity of ZIKV similar to dengue and chikungunya in Jamaica. A ZIKV vaccine, similar to the dengue and chikungunya vaccines, is needed to be fast-tracked into clinical trials to mitigate the effects of this disease.
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BACKGROUND: It is unclear whether more timely cancer diagnosis brings favourable outcomes, with much of the previous evidence, in some cancers, being equivocal. We set out to determine whether there is an association between time to diagnosis, treatment and clinical outcomes, across all cancers for symptomatic presentations. METHODS: Systematic review of the literature and narrative synthesis. RESULTS: We included 177 articles reporting 209 studies. These studies varied in study design, the time intervals assessed and the outcomes reported. Study quality was variable, with a small number of higher-quality studies. Heterogeneity precluded definitive findings. The cancers with more reports of an association between shorter times to diagnosis and more favourable outcomes were breast, colorectal, head and neck, testicular and melanoma. CONCLUSIONS: This is the first review encompassing many cancer types, and we have demonstrated those cancers in which more evidence of an association between shorter times to diagnosis and more favourable outcomes exists, and where it is lacking. We believe that it is reasonable to assume that efforts to expedite the diagnosis of symptomatic cancer are likely to have benefits for patients in terms of improved survival, earlier-stage diagnosis and improved quality of life, although these benefits vary between cancers.
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Diagnóstico Tardío/estadística & datos numéricos , Neoplasias , Tiempo de Tratamiento/estadística & datos numéricos , Humanos , Neoplasias/diagnóstico , Neoplasias/terapia , PronósticoRESUMEN
Perforating folliculitis (PF) describes the process by which altered dermal material is eliminated from the epidermis through a follicular unit resulting in keratotic, follicular papules that favor hair-bearing regions of the forearms, arms, buttocks, and thighs. Diabetes mellitus (DM) and chronic renal failure (CRF) are commonly associated with PF. The more general term, acquired perforating dermatosis, has been applied to PF as well as Kyrles disease and the non-inherited form of perforating collagenosis. In this report, we describe an instance of PF that arose in the setting of preexisting antisynthetase syndrome.
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The vast range of genetic diversity contributes to a wonderful array of human traits and characteristics. Unfortunately, a consequence of this genetic diversity is large variability in drug response between people, meaning that no single medication is safe and effective in everyone. The debilitating and sometimes deadly consequences of adverse drug reactions (ADRs) are a major and unmet problem of modern medicine. Pharmacogenomics can uncover associations between genetic variation and drug safety and has the potential to predict ADRs in individual patients. Here we review pharmacogenomic successes leading to changes in clinical practice, as well as clinical areas probably to be impacted by pharmacogenomics in the near future. We also discuss some of the challenges, and potential solutions, that remain for the implementation of pharmacogenomic testing into clinical practice for the significant improvement of drug safety.