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Obesity can increase the risk of bone fragility, even when bone mass is intact. This fragility stems from poor bone quality, potentially caused by deficiencies in bone matrix material properties. However, cellular and molecular mechanisms leading to obesity-related bone fragility are not fully understood. Using male mouse models of obesity, we discovered TGF-ß signaling plays a critical role in mediating the effects of obesity on bone. High-carbohydrate and high-fat diets increase TGF-ß signaling in osteocytes, which impairs their mitochondrial function, increases cellular senescence, and compromises perilacunar/canalicular remodeling and bone quality. By specifically inhibiting TGF-ß signaling in mouse osteocytes, some of the negative effects of high-fat and high-carbohydrate diets on bones, including the lacunocanalicular network, perilacunar/canalicular remodeling, senescence, and mechanical properties such as yield stress, were mitigated. DMP1-Cre-mediated deletion of TGF-ß receptor II also blunted adverse effects of high-fat and high-carbohydrate diets on energy balance and metabolism. These findings suggest osteocytes are key in controlling bone quality in response to high-fat and high-carbohydrate diets. Calibrating osteocyte function could mitigate bone fragility associated with metabolic diseases while reestablishing energy balance.
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Dieta Alta en Grasa , Obesidad , Osteocitos , Factor de Crecimiento Transformador beta , Animales , Osteocitos/metabolismo , Dieta Alta en Grasa/efectos adversos , Ratones , Factor de Crecimiento Transformador beta/metabolismo , Masculino , Obesidad/metabolismo , Transducción de Señal , Receptor Tipo II de Factor de Crecimiento Transformador beta/metabolismo , Receptor Tipo II de Factor de Crecimiento Transformador beta/genética , Remodelación Ósea , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Huesos/metabolismo , Densidad Ósea/efectos de los fármacos , Carbohidratos de la Dieta/efectos adversos , Carbohidratos de la Dieta/administración & dosificaciónRESUMEN
Background: Upper extremity sensory neuromas can be extremely debilitating leading to pain and dysfunction. Surgical management of neuromas can either be ablative or reconstructive. The primary aim of this study was to examine the outcomes of surgically treated sensory neuromas within the forearm, wrist, and hand with exclusion of digital neuromas. Methods: A retrospective review was conducted of patients surgically treated for an upper extremity sensory neuroma from a multi-surgeon, single institution database. The types of neuroma, mechanism of injury and the surgical technique utilized for treatment were documented. Patient reported outcomes were collected including resolution of symptoms, pain scores, complications, and need for revision surgery. Averages and proportions were used for analysis. Results: 79 patients were included with mean age of 42.3 years and an average follow-up of 6.7 months. The types of sensory neuromas included 23 dorsal radial sensory, 21 medial antebrachial cutaneous, 15 palmar cutaneous, and 14 dorsal ulnar sensory. Single isolated cases of neuromas were more common (94.9%) than multiple neuromas (5.1%). 67.1% (53/79) of patients experienced pain or hypersensitivity with a mean improvement of 2.0 in the visual analog scale (VAS) following surgery. 6.3% (5/79) required revision surgery, and 82% returned to work in some capacity. Conclusion: Surgical excision of neuroma and burial into local surrounding tissue can be safely performed with a relatively low reoperation rate. 80% of patients had full resolution or improvement in their symptoms.
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BACKGROUND: Children and youth with special health care needs (CYSHCN) are at an increased risk for abuse and neglect, and they experience worse outcomes during and after child protective services involvement, as compared to typically developing peers. Identifying and monitoring these vulnerable youth is essential for reducing disparities and optimizing service delivery. However, many states, including Illinois, lack systems for efficient identification and monitoring. OBJECTIVE: (1) To examine existing Illinois Department of Children and Family Services (ILDCFS) data systems to determine if a source exists that would allow for identification and monitoring of CYSHCN; and (2) To understand ILDCFS personnel's experience with identifying and monitoring CYSHCN. METHODS: First, relevant ILDCFS data sources were identified, pulled, and examined for completeness. Second, ILDCFS personnel completed a mixed-methods survey assessing how they identified and monitored CYSHCN as well as what barriers they experienced in conducting these activities. Conceptual content analysis was utilized to obtain counts of different methods used to track and monitor youth as well as to identify barriers to these processes. RESULTS: Six data sources were identified as being relevant through ILDCFS' data systems, but none were complete enough for effectively tracking and identifying CYSHCN. Survey responses indicated no standardized, systemic process for identifying and monitoring CYSHCN, with many personnel relying on reports from other involved parties. CONCLUSIONS: In order to identify CYSHCN and monitor well-being, a standardized process within ILDCFS systems is needed to provide complete, accurate, and timely data for CYSHCN, allowing for both system-wide and individual-level monitoring.
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Servicios de Salud del Niño , Niños con Discapacidad , Niño , Humanos , Adolescente , Illinois , Protección a la Infancia , Necesidades y Demandas de Servicios de Salud , Sistemas de InformaciónRESUMEN
Radial neck fractures are common injuries of the elbow in the pediatric patient. Surgical intervention is recommended for significant angulation and displacement or mechanical blocks to motion. Radial neck malunion is a rare complication and may result in altered joint mechanics and, if severe, joint incongruency. Dislocation of the radial head has yet to be reported in this population after radial neck malunion. Treatment for radial neck malunions with dislocation varies and can include radial head excision or radial neck osteotomy. Outcomes after radial neck osteotomy is limited to case reports and small cases series. We present a case report of pediatric patient with radial neck malunion and anterior radiocapitellar dislocation treated with joint realignment via opening wedge osteotomy. To our knowledge, this is the first report of a pediatric case with radial head dislocation secondary to neck malunion and the first described report using this technique.
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Purpose: To evaluate whether Spanish-speaking patients can obtain appointments to outpatient orthopaedic surgery clinics across the United States at a similar rate as English-speaking patients and to examine the language interpretation services available at those clinics. Methods: Orthopaedic offices nationwide were called by a bilingual investigator to request an appointment with a pre-established script. The investigators called in English asking for an appointment for an English-speaking patient (English-English), called in English requesting an appointment for a Spanish-speaking patient (English-Spanish), and called in Spanish asking for an appointment for a Spanish-speaking patient (Spanish-Spanish) in a random order. During each call whether an appointment was given, the number of days to the offered appointment, the mechanism of interpretation available in clinic, and whether the patient's citizenship or insurance information was requested was collected. Results: A total of 78 clinics included in the analysis. There was a statistically significant decrease in access to scheduling an orthopaedic appointment in the Spanish-Spanish group (26.3%) compared with English-English (61.3%) or English-Spanish (58.8%) groups (P < .001). There was no significant difference in access to appointment between rural and urban areas. Patients in the Spanish-Spanish group who made an appointment were offered in-person interpretation 55% of the time. There was no statistically significant difference in time from call to offered appointment or the request for citizenship status between the 3 groups. Conclusions: This study detected a considerable disparity regarding access to orthopaedic clinics nationwide in the individuals who called to establish an appointment in Spanish. Patients in the Spanish-Spanish group were able to make an appointment less often but had in-person interpreters available for interpretation services. Clinical Relevance: With a large Spanish-speaking population in the United States, it is important to understand how lack of proficiency with the English language may affect access to orthopaedic care. This study uncovers variables associated with difficulties scheduling appointments for Spanish-speaking patients.
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PURPOSE: Previous studies have shown that bariatric surgery reduces the risk of cardiovascular outcomes. Less is known about the effects of bariatric surgery on psychiatric disorders. This cohort study compared the differential risk of psychiatric disorders between those who did and did not undergo bariatric surgery, from before until after the surgery. MATERIALS AND METHODS: We used PearlDiver-Mariner, a national all-payor claims database. Patients were followed for 1 year before and after the index date and a difference-in-differences (DiD) study design was executed. RESULTS: We included 56,661 bariatric surgery patients matched to 56,661 individuals with obesity. Among bariatric surgery patients, the risk of psychiatric was 18% 1 year before and increased to 70% 1 year after surgery. Among individuals with obesity, the risk of psychiatric disorders also increased from 1 year before to 1 year after, but by less (21% versus 46%). DiD analysis suggested that bariatric surgery was associated with a 27 percentage point differential increase in the risk of psychiatric disorders across all patients, representing a 135% relative increase. Results using 3 years as the pre- and post-periods lead to similar inferences. CONCLUSION: Preexisting psychiatric disorders are similarly prevalent among bariatric surgery patients and individuals with obesity. The prevalence of psychiatric disorders increased over time for both groups, but to a larger extent among bariatric surgery patients. Adequate treatment for psychiatric disorders and appropriate implementation of behavioral health interventions may be needed to reduce the burden of psychiatric disorders following bariatric surgery.
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Cirugía Bariátrica , Trastornos Mentales , Obesidad Mórbida , Cirugía Bariátrica/psicología , Estudios de Cohortes , Humanos , Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Obesidad/complicaciones , Obesidad/cirugía , Obesidad Mórbida/cirugíaRESUMEN
BACKGROUND: Patients transferred between hospitals are at high risk of adverse events and mortality. The relationship between insurance status, transfer practices, and outcomes has not been definitively characterized. OBJECTIVE: To identify the association between insurance coverage and mortality of patients transferred between hospitals. DESIGN: We conducted a single-institution observational study, and validated results using a national administrative database of inter-hospital transfers. SETTING: Three ICUs at an academic tertiary care center validated by a nationally representative sample of inter-hospital transfers. PATIENTS: The single-institution analysis included 652 consecutive patients transferred from 57 hospitals between 2011 and 2012. The administrative database included 353,018 patients transferred between 437 hospitals. MEASUREMENTS: Adjusted inpatient mortality and 24-h mortality, stratified by insurance status. RESULTS: Of 652 consecutive transfers to three ICUs, we observed that uninsured patients had higher adjusted inpatient mortality (OR 2.67, p = 0.021) when controlling for age, race, gender, Apache-II, and whether the patient was transferred from an ED. Uninsured were more likely to be transferred from ED (OR 2.3, p = 0.026), and earlier in their hospital course (3.9 vs 2.0 days, p = 0.002). Using an administrative dataset, we validated these observations, finding that the uninsured had higher adjusted inpatient mortality (OR 1.24, 95% CI 1.13-1.36, p < 0.001) and higher mortality within 24 h (OR 1.33 95% CI 1.11-1.60, p < 0.002). The increase in mortality was independent of patient demographics, referral patterns, or diagnoses. LIMITATIONS: This is an observational study where transfer appropriateness cannot be directly assessed. CONCLUSIONS: Uninsured patients are more likely to be transferred from an ED and have higher mortality. These data suggest factors that drive inter-hospital transfer of uninsured patients have the potential to exacerbate outcome disparities.
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Disparidades en Atención de Salud/tendencias , Cobertura del Seguro/tendencias , Mortalidad/tendencias , Transferencia de Pacientes/tendencias , Centros de Atención Terciaria/tendencias , Adulto , Anciano , Estudios Transversales , Bases de Datos Factuales/tendencias , Femenino , Predicción , Humanos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
BACKGROUND: Interhospital transfer is an understudied area within transitions of care. The process by which hospitals accept and transfer patients is not well described. National trends and best practices are unclear. OBJECTIVE: To describe the demographics of large transfer centers, to identify common handoff practices, and to describe challenges and notable innovations involving the interhospital transfer handoff process. DESIGN AND PARTICIPANTS: A convenience sample of 32 tertiary care centers in the United States was studied. Respondents were typically transfer center directors surveyed by phone. MAIN MEASURES: Data regarding transfer center demographics, handoff communication practices, electronic infrastructure, and data sharing were obtained. RESULTS: The median number of patients transferred each month per receiving institution was 700 (range, 250-2500); on average, 28% of these patients were transferred to an intensive care unit. Transfer protocols and practices varied by institution. Transfer center coordinators typically had a medical background (78%), and critical care-trained registered nurse was the most prevalent (38%). Common practices included: mandatory recorded 3-way physician-to-physician conversation (84%) and mandatory clinical status updates prior to patient arrival (81%). However, the timeline of clinical status updates was variable. Less frequent transfer practices included: electronic medical record (EMR) cross-talk availability and utilization (23%), real-time transfer center documentation accessibility in the EMR (32%), and referring center clinical documentation available prior to transport (29%). A number of innovative strategies to address challenges involving interhospital handoffs are reported. CONCLUSIONS: Interhospital transfer practices vary widely amongst tertiary care centers. Practices that lead to improved patient handoffs and reduced medical errors need additional prospective evaluation. Journal of Hospital Medicine 2016;11:413-417. © 2016 Society of Hospital Medicine.
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Pase de Guardia/organización & administración , Transferencia de Pacientes/normas , Centros de Atención Terciaria , Comunicación , Documentación/normas , Humanos , Unidades de Cuidados Intensivos , Transferencia de Pacientes/métodos , Estudios Prospectivos , Encuestas y Cuestionarios , Estados UnidosRESUMEN
PURPOSE: We assessed the safety and efficacy of synchronous VEGF and epidermal growth factor receptor (EGFR) blockade with concurrent chemoradiation (CRT) in locally advanced head and neck cancer (HNC). EXPERIMENTAL DESIGN: Newly diagnosed patients with stage III/IV HNC received a 2-week lead-in of bevacizumab and/or erlotinib, followed by both agents with concurrent cisplatin and twice daily radiotherapy. Safety was assessed using Common Toxicity Criteria version 3.0. The primary efficacy endpoint was clinical complete response (CR) rate after CRT. RESULTS: Twenty-nine patients enrolled on study, with 27 completing therapy. Common grade III toxicities were mucositis (n = 14), dysphagia (n = 8), dehydration (n = 7), osteoradionecrosis (n = 3), and soft tissue necrosis (n = 2). Feeding tube placement was required in 79% but no patient remained dependent at 12-month posttreatment. Clinical CR after CRT was 96% [95% confidence interval (CI), 82%-100%]. Median follow-up was 46 months in survivors, with 3-year locoregional control and distant metastasis-free survival rates of 85% and 93%. Three-year estimated progression-free survival, disease-specific survival, and overall survival rates were 82%, 89%, and 86%, respectively. Dynamic contrast enhanced MRI (DCE-MRI) analysis showed that patients who had failed had lower baseline pretreatment median K(trans) values, with subsequent increases after lead-in therapy and 1 week of CRT. Patients who did not fail had higher median K(trans) values that decreased during therapy. CONCLUSIONS: Dual VEGF/EGFR inhibition can be integrated with CRT in locally advanced HNC, with efficacy that compares favorably with historical controls albeit with an increased risk of osteoradionecrosis. Pretreatment and early DCE-MRI may prospectively identify patients at high risk of failure.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia , Neoplasias de Cabeza y Cuello/terapia , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab , Terapia Combinada , Clorhidrato de Erlotinib , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Quinazolinas/administración & dosificación , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: Dynamic contrast-enhanced (DCE) MRI-extracted parameters measure tumor microvascular physiology and are usually calculated from an intratumor region of interest (ROI). Optimal ROI delineation is not established. The valid clinical use of DCE-MRI requires that the variation for any given parameter measured within a tumor be less than that observed between tumors in different patients. This work evaluates the impact of tumor ROI selection on the assessment of intra- and interpatient variability. METHOD AND MATERIALS: Head and neck cancer patients received initial targeted therapy (TT) treatment with erlotinib and/or bevacizumab, followed by radiotherapy and concurrent cisplatin with synchronous TT. DCE-MRI data from Baseline and the end of the TT regimen (Lead-In) were analyzed to generate the vascular transfer function (K(trans)), the extracellular volume fraction (v(e)), and the initial area under the concentration time curve (iAUC(1 min)). Four ROI sampling strategies were used: whole tumor or lymph node (Whole), the slice containing the most enhancing voxels (SliceMax), three slices centered in SliceMax (Partial), and the 5% most enhancing contiguous voxels within SliceMax (95Max). The average coefficient of variation (aCV) was calculated to establish intrapatient variability among ROI sets and interpatient variability for each ROI type. The average ratio between each intrapatient CV and the interpatient CV was calculated (aRCV). RESULTS: Baseline primary/nodes aRCVs for different ROIs not including 95Max were, for all three MR parameters, in the range of 0.14-0.24, with Lead-In values between 0.09 and 0.2, meaning a low intrapatient vs. interpatient variation. For 95Max, intrapatient CVs approximated interpatient CVs, meaning similar data dispersion and higher aRCVs (0.6-1.27 for baseline) and 0.54-0.95 for Lead-In. CONCLUSION: Distinction between different patient's primary tumors and/or nodes cannot be made using 95Max ROIs. The other three strategies are viable and equivalent for using DCE-MRI to measure head and neck cancer physiology.
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Medios de Contraste/farmacocinética , Gadolinio DTPA/farmacocinética , Neoplasias de Cabeza y Cuello/irrigación sanguínea , Aumento de la Imagen/métodos , Imagen por Resonancia Magnética/métodos , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Área Bajo la Curva , Bevacizumab , Quimioradioterapia/métodos , Cisplatino/uso terapéutico , Clorhidrato de Erlotinib , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Humanos , Metástasis Linfática , Microcirculación , Terapia Molecular Dirigida/métodos , North Carolina , Quinazolinas/uso terapéuticoRESUMEN
INTRODUCTION: Bevacizumab is increasingly being tested with neoadjuvant regimens in patients with localized cancer, but its effects on metastasis and survival remain unknown. This study examines the long-term outcome of clinical stage II/III rectal cancer patients treated in a prospective phase II study of bevacizumab with chemoradiation and surgery. As a benchmark, we used data from an analysis of 42 patients with locally advanced rectal cancer treated with a contemporary approach of preoperative fluoropyrimidine-based radiation therapy. MATERIALS AND METHODS: Outcome analyses were performed on 32 patients treated prospectively with neoadjuvant bevacizumab, 5-fluorouracil, radiation therapy, and surgery as well as 42 patients treated with standard fluoropyrimidine-based chemoradiation. RESULTS: Overall survival, disease-free survival, and local control showed favorable trends in patients treated with bevacizumab with chemoradiation followed by surgery. Acute and postoperative toxicity appeared acceptable. CONCLUSIONS: Neoadjuvant bevacizumab with standard chemoradiation and surgery shows promising long-term efficacy and safety profiles in locally advanced rectal cancer patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Recto/terapia , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Bevacizumab , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estudios Prospectivos , Neoplasias del Recto/patología , Análisis de Supervivencia , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
PURPOSE: Calculation of the precontrast longitudinal relaxation times (T10) is an integral part of the Tofts-based pharmacokinetic (PK) analysis of dynamic contrast enhanced-magnetic resonance images. The purpose of this study was to investigate the interpatient and over time variability of T10 in head and neck primary tumors and involved nodes and to determine the median T10 for primary and nodes (T10(p,n)). The authors also looked at the implication of using voxel-based T10 values versus region of interest (ROI)-based T10 on the calculated values for vascular permeability (K(trans)) and extracellular volume fraction (v(e)). METHODS: Twenty head and neck cancer patients receiving concurrent chemoradiation and molecularly targeted agents on a prospective trial comprised the study population. Voxel-based T10's were generated using a gradient echo sequence on a 1.5 T MR scanner using the variable flip angle method with two flip angles [J. A. Brookes et al., "Measurement of spin-lattice relaxation times with FLASH for dynamic MRI of the breast," Br. J. Radiol. 69, 206-214 (1996)]. The voxel-based T10, K(trans), and v(e) were calculated using iCAD's (Nashua, NH) software. The mean T10's in muscle and fat ROIs were calculated (T10(m,f)). To assess reliability of ROI drawing, T10(p,n) values from ROIs delineated by 2 users (A and B) were calculated as the average of the T10's for 14 patients. For a subset of three patients, the T10 variability from baseline to end of treatment was also investigated. The K(trans) and v(e) from primary and node ROIs were calculated using voxel-based T10 values and T10(p,n) and differences reported. RESULTS: The calculated T10 values for fat and muscle are within the range of values reported in literature for 1.5 T, i.e., T10(m) = 0.958 s and T10(f) = 0.303 s. The average over 14 patients of the T10's based on drawings by users A and B were T10(pA) = 0.804 s, T10(nA) = 0.760 s, T10(pB) = 0.849 s, and T10(nB) = 0.810 s. The absolute percentage difference between K(trans) and v(e) calculated with voxel-based T10 versus T10(p,n) ranged from 6% to 81% and from 2% to 24%, respectively. CONCLUSIONS: There is a certain amount of variability in the median T10 values between patients, but the differences are not significant. There were also no statistically significant differences between the T10 values for primary and nodes at baseline and the subsequent time points (p = 0.94 Friedman test). Voxel-based T10 calculations are essential when quantitative Tofts-based PK analysis in heterogeneous tumors is needed. In the absence of T10 mapping capability, when a relative, qualitative analysis is deemed sufficient, a value of T10(p,n) = 0.800 s can be used as an estimate for T10 for both the primary tumor and the affected nodes in head and neck cancers at all the time points considered.
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Gadolinio DTPA , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/terapia , Imagen por Resonancia Magnética/métodos , Medios de Contraste , Humanos , Aumento de la Imagen/métodos , Estudios Longitudinales , Pronóstico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
We explored plasma and urinary concentrations of two members of the vascular endothelial growth factor (VEGF) family and their receptors as potential response and toxicity biomarkers of bevacizumab with neoadjuvant chemoradiation in patients with localized rectal cancer. The concentrations of VEGF, placental growth factor (PlGF), soluble VEGF receptor 1 (sVEGFR-1), and sVEGFR-2 were measured in plasma and urine at baseline and during treatment. Pretreatment values and changes over time were analyzed as potential biomarkers of pathological response to treatment as well as for acute toxicity in patients with locally advanced rectal cancer treated prospectively in 2002-2008 with neoadjuvant bevacizumab, 5-fluorouracil, radiation therapy, and surgery in a phase I/II trial. Of all biomarkers, pretreatment plasma sVEGFR-1-an endogenous blocker of VEGF and PlGF, and a factor linked with "vascular normalization"-was associated with both primary tumor regression and the development of adverse events after neoadjuvant bevacizumab and chemoradiation. Based on the findings in this exploratory study, we propose that plasma sVEGFR-1 should be further studied as a potential biomarker to stratify patients in future studies of bevacizumab and/or cytotoxics in the neoadjuvant setting.