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BACKGROUND: The Multicenter Selective Lymphadenectomy Trial-II (MSLT-II) revealed completion lymph node dissection (CLND) after positive sentinel lymph node biopsy (SLNB) did not improve melanoma-specific survival compared with surveillance. Given these findings and the morbidity associated with CLND, this study investigated trends in rates and predictors of CLND after MSLT-II. METHODS: Analysis of the National Cancer Database was performed for all patients aged ≥18 years with melanoma and a positive SLNB for 2012-2019. Rates of CLND before and after publication of MSLT-II were identified and logistic regression used to identify factors associated with CLND. RESULTS: Patients undergoing CLND declined from 55.9% pre-MSLT-II (n = 9725) to 19.5% post-MSLT-II (n = 9419) (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.29-0.35). CLND was less likely in females (OR 0.83; 95% CI 0.78-0.89), older patients (vs. 18-39 yr; 40-64 yr OR 0.80, 95% CI 0.65-0.98; 65-79 yr OR 0.67, 95% CI 0.53-0.84; >80 yr OR 0.38, 95% CI 0.30-0.49), sicker patients (Deyo category ≥2 OR 0.85, 95% CI 0.73-0.99), thinner primary lesions (vs. 0.01-0.79 mm; 1.01-4.00 mm OR 1.16, 95% CI 1.01-1.33; ≥4.01 mm OR 1.31, 95% CI 1.08-1.59), patients from metro areas (Rural OR 1.31, 95% CI 1.00-1.70; Urban OR 1.15, 95% CI 1.03-1.29), and those treated at lower-volume centers (vs. lowest-volume; highest-volume OR 1.31, 95% CI 1.14-1.50; high-volume OR 1.40, 95% CI 1.24-1.57). CONCLUSIONS: MSLT-II has impacted clinical care; however, male gender, thicker lesions, rural/urban residence, younger age, fewer comorbidities, and treatment at higher-volume centers confer a greater likelihood of undergoing CLND. Further investigations should focus on whether these populations benefit from more aggressive surgical care.
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Melanoma , Linfonodo Sentinela , Neoplasias Cutâneas , Feminino , Humanos , Masculino , Estados Unidos/epidemiologia , Adolescente , Adulto , Melanoma/patologia , Excisão de Linfonodo , Biópsia de Linfonodo Sentinela , Bases de Dados Factuais , Probabilidade , Neoplasias Cutâneas/patologia , Linfonodo Sentinela/patologiaRESUMO
BACKGROUND: Medicaid expansion improved insurance coverage for patients with chronic conditions and low income. The effect of Medicaid expansion on patients with IBD from high-poverty communities is unknown. OBJECTIVE: This study aimed to evaluate the impact of Medicaid expansion in Kentucky on care for patients with IBD from the Eastern Kentucky Appalachian community, a historically impoverished area. DESIGN: This study was a retrospective, descriptive, and ecological study. SETTINGS: This study was conducted in Kentucky using the Hospital Inpatient Discharge and Outpatient Services Database. PATIENTS: All encounters for IBD care for 2009-2020 for patients from the Eastern Kentucky Appalachian region were included. MAIN OUTCOME MEASURES: The primary outcomes measured were proportions of inpatient and emergency encounters, total hospital charge, and hospital length of stay. RESULTS: Eight hundred twenty-five preexpansion and 5726 postexpansion encounters were identified. Postexpansion demonstrated decreases in the uninsured (9.2%-1.0%; p < 0.001), inpatient encounters (42.7%-8.1%; p < 0.001), emergency admissions (36.7%-12.3%; p < 0.001), admissions from the emergency department (8.0%-0.2%; p < 0.001), median total hospital charge ($7080-$3260; p < 0.001), and median total hospital length of stay (4-3 days; p < 0.001). Similarly, postexpansion demonstrated increases in Medicaid coverage (18.8%-27.7%; p < 0.001), outpatient encounters (57.3%-91.9%; p < 0.001), elective admissions (46.9%-76.2%; p < 0.001), admissions from the clinic (78.4%-90.2%; p < 0.001), and discharges to home (43.8%-88.2%; p < 0.001). LIMITATIONS: This study is subject to the limitations inherent in being retrospective and using a partially de-identified database. CONCLUSION: This study is the first to demonstrate the changes in trends in care after Medicaid expansion for patients with IBD in the Commonwealth of Kentucky, especially Appalachian Kentucky, showing significantly increased outpatient care utilization, reduced emergency department encounters, and decreased length of stays. IMPACTO DE LA LEY DEL CUIDADO DE SALUD A BAJO PRECIO EN LA PROVISIN DE ACCESO EQUITATIVO A LA ATENCIN MDICA PARA LA ENFERMEDAD INFLAMATORIA INTESTINAL EN LA REGIN DE LOS APALACHES DE KENTUCKY: ANTECEDENTES: La expansión de Medicaid mejoró la cobertura de seguro para pacientes con enfermedades crónicas y bajos ingresos. Se desconoce el efecto de la expansión de Medicaid en pacientes con enfermedad inflamatoria intestinal de comunidades de alta pobreza.OBJETIVO: Este estudio tuvo como objetivo evaluar el impacto de la expansión de Medicaid en Kentucky en la atención de pacientes con enfermedad inflamatoria intestinal de la comunidad de los Apalaches del este de Kentucky, un área históricamente empobrecida.DISEÑO: Este estudio fue un estudio retrospectivo, descriptivo, ecológico.ESCENARIO: Este estudio se realizó en Kentucky utilizando la base de datos de servicios ambulatorios y de alta hospitalaria en pacientes hospitalizados.PACIENTES: Se incluyeron todos los encuentros para la atención de la enfermedad inflamatoria intestinal de 2009-2020 para pacientes de la región de los Apalaches del este de Kentucky.MEDIDAS DE RESULTADO PRINCIPALES: Los resultados primarios medidos fueron proporciones de encuentros de pacientes hospitalizados y de emergencia, cargo hospitalario total y duración de la estancia hospitalaria.RESULTADOS: Se identificaron 825 encuentros previos a la expansión y 5726 posteriores a la expansión. La posexpansión demostró disminuciones en los no asegurados (9.2% a 1.0%, p < 0.001), encuentros de pacientes hospitalizados (42.7% a 8.1%, p < 0.001), admisiones de emergencia (36.7% a 12.3%, p < 0,001), admisiones desde el servicio de urgencias (8.0% a 0.2%, p < 0.001), la mediana de los gastos hospitalarios totales ($7080 a $3260, p < 0.001) y la mediana de la estancia hospitalaria total (4 a 3 días, p < 0.001). De manera similar, la cobertura de Medicaid (18.8% a 27.7%, p < 0.001), consultas ambulatorias (57.3% a 91.9%, p < 0.001), admisiones electivas (46.9% a 76.2%, p < 0.001), admisiones desde la clínica (78.4% al 90.2%, p < 0.001), y las altas domiciliarias (43.8% al 88.2%, p < 0.001) aumentaron después de la expansión.LIMITACIONES: Este estudio está sujeto a las limitaciones inherentes de ser retrospectivo y utilizar una base de datos parcialmente desidentificada.CONCLUSIONES: Este estudio es el primero en demostrar los cambios en las tendencias en la atención después de la expansión de Medicaid para pacientes con enfermedad inflamatoria intestinal en el Estado de Kentucky, especialmente en los Apalaches de Kentucky, mostrando un aumento significativo en la utilización de la atención ambulatoria, visitas reducidas al departamento de emergencias y menor duración de la estancia hospitalaria. (Traducción-Dr. Jorge Silva Velazco ).
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Doenças Inflamatórias Intestinais , Patient Protection and Affordable Care Act , Estados Unidos/epidemiologia , Humanos , Kentucky/epidemiologia , Estudos Retrospectivos , Região dos Apalaches/epidemiologia , Acessibilidade aos Serviços de Saúde , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Complicações Pós-OperatóriasRESUMO
INTRODUCTION: Appropriate prescribing practices are imperative to ensure adequate pain control, without excess opioid dispensing across colorectal patients. METHODS: National Surgical Quality Improvement Program, Kentucky All Scheduled Prescription Electronic Reporting, and patient charts were queried to complete a retrospective study of elective colorectal resections, performed by a fellowship-trained colorectal surgeon, from January 2013 to December 2020. Opioid use at 14 d and 30 d posthospital discharge converted into morphine milligram equivalents (MMEs) were analyzed and compared across preadmission and inpatient factors. RESULTS: One thousand four hundred twenty seven colorectal surgeries including 56.1% (N = 800) partial colectomy, 24.1% (N = 344) low anterior resection, 8.3% (N = 119) abdominoperineal resection, 8.4% (N = 121) sub/total colectomy, and 3.0% (N = 43) total proctocolectomy. Abdominoperineal resection and sub/total colectomy patients had higher 30-day postdischarge MMEs (P < 0.001, P = 0.041). An operative approach did not affect postdischarge MMEs (P = 0.440). Trans abdominal plane blocks do not predict postdischarge MMEs (0.616). Epidural usage provides a 15% increase in postdischarge MMEs (P = 0.020). Age (P < 0.001), smoking (P < 0.001), chronic obstructive pulmonary disease (P = 0.006, < 0.001), dyspnea (P = 0.001, < 0.001), albumin < 3.5 (P = 0.085, 0.010), disseminated cancer (P = 0.018, 0.001), and preadmission MMEs (P < 0.001) predict elevated 14-day and 30-day postdischarge MMEs. CONCLUSIONS: We conclude that perioperative analgesic procedures, as enhanced recovery pathway suggests, are neither predictive nor protective of postoperative discharge MMEs in colorectal surgery. Provider should account for preoperative risk factors when prescribing discharge opioid medications. Furthermore, providers should identify appropriate adjunct procedures to improve discharge opioid prescription stewardship.
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Neoplasias Colorretais , Transtornos Relacionados ao Uso de Opioides , Humanos , Analgésicos Opioides/efeitos adversos , Estudos Retrospectivos , Dor Pós-Operatória/etiologia , Assistência ao Convalescente , Alta do Paciente , Transtornos Relacionados ao Uso de Opioides/etiologia , Fatores de Risco , Neoplasias Colorretais/tratamento farmacológico , Padrões de Prática MédicaRESUMO
INTRODUCTION: Although surgical site infections (SSIs) associated with colectomy are tracked by the National Healthcare Safety Network/Center for Disease Control, untracked codes, mainly related to patients undergoing proctectomy, are not. These untracked codes are performed less often yet they may be at a greater risk of SSI due to their greater complexity. Determining the impact and predictors of SSI are critical in the development of quality improvement initiatives. METHODS: Following an institutional review board approval, National Surgery Quality Improvement Program, institutional National Surgery Quality Improvement Program, and financial databases were queried for tracked colorectal resections and untracked colorectal resections (UCR). National data were obtained for January 2019-December 2019, and local procedures were identified between January 2013 and December 2019. Data were analyzed for preoperative SSI predictors, operative characteristics, outcomes, and 30-day postdischarge costs (30dPDC). RESULTS: Nationally, 71,705 colorectal resections were identified, and institutionally, 2233 patients were identified. UCR accounted for 7.9% nationally and 11.8% of all colorectal resections institutionally. Tracked colorectal resection patients had a higher incidence of SSI predictors including sepsis, hypoalbuminemia, coagulopathy, hypertension, and American Society of Anesthesiologists class. UCR patients had a higher rate of SSIs [12.9% (P < 0.001), 15.2% (P = 0.064)], readmission, and unplanned return to the operating room. Index hospitalization and 30dPDC were significantly higher in patients experiencing an SSI. CONCLUSIONS: SSI was associated with nearly a two-fold increase in index hospitalization costs and six-fold in 30dPDC. These data suggest opportunities to improve hospitalization costs and outcomes for patients undergoing UCR through protocols for SSI reduction and preventing readmissions.
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Neoplasias Colorretais , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Assistência ao Convalescente , Fatores de Risco , Alta do Paciente , Neoplasias Colorretais/complicações , Estudos RetrospectivosRESUMO
BACKGROUND: Laparoscopic pyloromyotomy is the preferred surgical management of hypertrophic pyloric stenosis at most centers. We aimed to analyze the learning curve for laparoscopic pyloromyotomy using the experience of five fellowship-trained pediatric surgeons. METHODS: A retrospective review of consecutive patients undergoing laparoscopic pyloromyotomy was performed. All cases were performed with general surgery residents. Cumulative sum (CUSUM) analysis for operating time was performed for up to the first 150 consecutive cases for individual surgeons. Outcomes were compared to identify different phases of the learning curve for operative competency. RESULTS: A total of 414 patients were included in the analysis as not all surgeons had reached 150 cases at time of analysis. The mean operating time was 29.2 min for all cases across the 5 surgeons. CUSUM analysis for mean operating time revealed three phases of learning: Learning Phase (cases 1-16), Plateau Phase (cases 17-87), and a Proficiency Phase (cases 88-150). The mean operating time during the three phases was 34.1, 29.0, and 28.3 min, respectively (P = 0.005). There were no differences in complications, reoperations, length of stay, or readmissions across the three phases. CONCLUSION: Three distinct phases of learning for laparoscopic pyloromyotomy were identified with no differences in outcomes across the phases. The operating time differed only for the Learning Phase, suggesting that some degree of proficiency occurs after 16 cases.
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Laparoscopia , Estenose Pilórica Hipertrófica , Piloromiotomia , Cirurgiões , Criança , Humanos , Curva de Aprendizado , Estenose Pilórica Hipertrófica/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Kingella kingae is an important cause of septic arthritis in young children, with modern laboratory methods leading to increased detection. Prevalence of this pathogen in New Zealand, where there are high rates of childhood infections due to Staphylococcus aureus and Streptococcus pyogenes, is not known. METHODS: We conducted a retrospective review of children <5 years with septic arthritis (without osteomyelitis) at a tertiary children's hospital in Auckland, over 10 years (2005-2014). Data were collected on demographics, microbiology, clinical presentation, investigations and management. RESULTS: Of the 68 cases of septic arthritis, 57 (83.8%) occurred in children aged <24 months. Among those <3 months, Streptococcus agalactiae (Group B streptococcus) was predominant (45.5% of 11 cases), followed by S. aureus (36.4%). The most common pathogen in those 3 to <12 months was Streptococcus pneumoniae (38.5% of 13 cases). In children aged 12 to <24 months, K. kingae was most common (30.3% of 33 cases). Of the 12 cases of K. kingae, 91.7% were identified from synovial fluid culture. All K. kingae isolates were susceptible to amoxicillin. CONCLUSIONS: K. kingae is the leading pathogen in septic arthritis in New Zealand children aged 12 to <24 months. Routine inoculation of synovial fluid into blood culture bottles at time of sample collection, in addition to use of polymerase chain reaction methods, should be encouraged to improve detection rates. For infants and preschool children presenting with single joint septic arthritis, empiric antibiotics should include cover for S. aureus and K. kingae.
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Artrite Infecciosa , Kingella kingae , Infecções por Neisseriaceae , Osteomielite , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/epidemiologia , Criança , Pré-Escolar , Humanos , Lactente , Infecções por Neisseriaceae/epidemiologia , Osteomielite/microbiologia , Staphylococcus aureusRESUMO
We have been publishing real-time forecasts of confirmed cases and deaths from coronavirus disease 2019 (COVID-19) since mid-March 2020 (published at www.doornik.com/COVID-19). These forecasts are short-term statistical extrapolations of past and current data. They assume that the underlying trend is informative regarding short-term developments but without requiring other assumptions about how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is spreading, or whether preventative policies are effective. Thus, they are complementary to the forecasts obtained from epidemiological models. The forecasts are based on extracting trends from windows of data using machine learning and then computing the forecasts by applying some constraints to the flexible extracted trend. These methods have been applied previously to various other time series data and they performed well. They have also proved effective in the COVID-19 setting where they provided better forecasts than some epidemiological models in the earlier stages of the pandemic.
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BACKGROUND: Prescription opioid, sedative, and antidepressant use has been on the rise. The effect of these medications on outcomes in colorectal surgery has not been established. OBJECTIVE: This study aimed to evaluate the impact of preoperative prescription opioid, sedative, and antidepressant use on postoperative outcomes following colorectal surgery. DESIGN: This study was a retrospective database and medical record review. SETTINGS: This study was conducted at University of Kentucky utilizing the local American College of Surgeons National Surgical Quality Improvement Project database. PATIENTS: All patients ≥18 years of age who underwent colorectal resection for all indications, excluding trauma, between January 1, 2013, and December 31, 2016, were included. MAIN OUTCOME MEASURES: The primary outcomes measured were the rates of 30-day postoperative morbidity and mortality. RESULTS: Of 1201 patients, 30.2% used opioids, 18.4% used sedatives, and 28.3% used antidepressants preoperatively. Users of any medication class had higher ASA classification, rates of dyspnea, and severe chronic obstructive pulmonary disease than nonusers. Opioid users also had higher rates of ostomy creation, contaminated wound classification, prolonged operation time, and postoperative transfusion. Postoperatively, patients had higher rates of intra-abdominal infection (opioids: 21.5% vs 15.2%, p = 0.009; sedatives: 23.1% vs 15.7%, p = 0.01; antidepressants: 22.4% vs 15.0%, p = 0.003) and respiratory failure (opioids: 11.0% vs 6.3%, p = 0.007; sedatives: 12.2% vs 6.7%, p = 0.008; antidepressants: 10.9% vs 6.5%, p = 0.02). Reported opioid or sedative users had a prolonged hospital length of stay of 2 days (p < 0.001) compared with nonusers. After adjustment for all predictors of poor outcome, opioid and sedative use was associated with increased 30-day morbidity and mortality following colorectal procedures (OR, 1.43; 95% CI, 1.07-1.91 and OR, 1.48; 95% CI, 1.05-2.08). LIMITATIONS: This study was a retrospective review and a single-institution study, and it had unmeasured confounders. CONCLUSIONS: We identified that patient-reported prescription opioid and sedative use is associated with higher 30-day composite adverse outcomes in colorectal resections, highlighting the need for the evaluation of opioid and sedative use as a component of the preoperative risk stratification. See Video Abstract at http://links.lww.com/DCR/B226. REVISIÓN RETROSPECTIVA: EL USO DE OPIOIDES, SEDANTES O ANTIDEPRESORES EN EL PREOPERATORIO SE ASOCIAN CON MALOS RESULTADOS EN CIRUGÍA COLORECTAL: El uso de opioides, sedantes y antidepresores esta en aumento. No se ha establecido el efecto de estos medicamentos en los resultados de la cirugía colorrectal.Evaluar el impacto del uso preoperatorio de opioides, sedantes y antidepresores en los resultados después de una cirugía colorrectal.Base de datos retrospectiva y revisión de registros médicos.Este estudio se realizó en la Universidad de Kentucky utilizando la base de datos del Proyecto de Mejora de Calidad Quirúrgica Nacional del Colegio Estadounidense de Cirujanos.Todos los pacientes ≥ 18 años que se sometieron a una resección colorrectal por diversas indicaciones, excluyendo los traumas, entre el 1 de Enero de 2013 y el 31 de Diciembre de 2016.Tasas de morbilidad y mortalidad postoperatorias a los 30 días.De 1201 pacientes, 30.2% usaron opioides, 18.4% usaron sedantes y 28.3% usaron antidepresores antes de la cirugía. Los pacientes tratados con cualquiera de los medicamentos mencionados, presentaban un ASA mas elevado, tasas de disnea y EPOC mas graves en comparación con pacientes sin tratamiento previo. Los consumidores de opioides también tuvieron tasas más altas de creación de ostomías, clasificación mas alta de heridas contaminadas, un tiempo de operación prolongado y transfusión postoperatoria mayor. Después de la cirugía los pacientes que tuvieron tasas más altas de infección intraabdominal (opioides: 21.5% vs 15.2%, p = 0.009, sedantes: 23.1% vs 15.7%, p = 0.01, antidepresivos: 22.4% vs 15.0%, p = 0.003) e insuficiencia respiratoria (opioides: 11.0% vs 6.3%, p = 0.007, sedantes: 12.2% vs 6.7%, p = 0.008, antidepresivos: 10.9% vs 6.5%, p = 0.02). Los consumidores de opioides o sedantes tuvieron una estadía hospitalaria prolongada de más de 2 días (p <0.001) en comparación con los consumidores. Después de haber realizado el ajuste de todos los predictores de mal pronóstico, el uso de opioides y sedantes se asoció con una mayor morbilidad y mortalidad a los 30 días después de cirugía colorrectal (OR 1.43 [IC 95% 1.07-1.91] y OR 1.48 [IC 95% 1.05-2.08], respectivamente)Revisión retrospectiva, estudio de una sola institución, factores de confusión no evaluados.Identificamos que el consumo de opiáceos y sedantes recetados a los pacientes se asocian con resultados adversos complejos más allá de 30 días en casos de resección colorrectal, destacando la necesidad de su respectiva evaluación como componentes de la estratificación de riesgo preoperatorio. Consulte Video Resumen http://links.lww.com/DCR/B226. (Traducción-Dr. Xavier Delgadillo).
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Analgésicos Opioides/efeitos adversos , Cirurgia Colorretal/estatística & dados numéricos , Hipnóticos e Sedativos/efeitos adversos , Cuidados Pré-Operatórios/métodos , Adulto , Idoso , Antidepressivos/efeitos adversos , Estudos de Casos e Controles , Cirurgia Colorretal/métodos , Dispneia/epidemiologia , Feminino , Humanos , Infecções Intra-Abdominais/epidemiologia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Medidas de Resultados Relatados pelo Paciente , Complicações Pós-Operatórias/mortalidade , Prescrições/estatística & dados numéricos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Melhoria de Qualidade , Insuficiência Respiratória/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Kentucky was among the first to adopt Medicaid expansion, resulting in reducing uninsured rates from 14.3% to 6.4%. We hypothesize that Medicaid expansion resulted in increased elective healthcare utilization and reductions in emergency treatments by patients suffering Inflammatory Bowel Disease (IBD). METHODS: The Hospital Inpatient Discharge and Outpatient Services Database (HIDOSD) identified all encounters related to IBD from 2009 to 2020 in Kentucky. Several demographic variables were compared in pre- and post-Medicaid expansion adoption. RESULTS: Our study analyzed 3386 pre-expansion and 24,255 post-expansion encounters for IBD patients. Results showed that hospitalization rates dropped (47.7%-8.4%), outpatient visits increased (52.3%-91.6%) and Emergency visits decreased (36.7%-11.4%). Admission following a clinical referral similarly increased with a corresponding drop in emergency room admissions. Hospital costs and lengths of stay also dropped following Medicaid expansion. CONCLUSION: In the IBD population, Medicaid expansion improved access to preventative care, reduced hospital costs by decreasing emergency care, and increased elective care pathways.
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Doenças Inflamatórias Intestinais , Medicaid , Aceitação pelo Paciente de Cuidados de Saúde , Humanos , Medicaid/estatística & dados numéricos , Estados Unidos , Masculino , Feminino , Adulto , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/economia , Kentucky , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Adulto Jovem , Estudos Retrospectivos , Patient Protection and Affordable Care Act , AdolescenteRESUMO
Ribonucleotide Reductase (RNR) is a rate-limiting enzyme in the production of deoxyribonucleoside triphosphates (dNTPs), which are essential substrates for DNA repair after radiation damage. We explored the radiosensitization property of RNR and investigated a selective RRM2 inhibitor, 3-AP, as a radiosensitizer in the treatment of metastatic pNETs. We investigated the role of RNR subunit, RRM2, in pancreatic neuroendocrine (pNET) cells and responses to radiation in vitro. We also evaluated the selective RRM2 subunit inhibitor, 3-AP, as a radiosensitizer to treat pNET metastases in vivo. Knockdown of RNR subunits demonstrated that RRM1 and RRM2 subunits, but not p53R3, play significant roles in cell proliferation. RRM2 inhibition activated DDR pathways through phosphorylation of ATM and DNA-PK protein kinases but not ATR. RRM2 inhibition also induced Chk1 and Chk2 phosphorylation, resulting in G1/S phase cell cycle arrest. RRM2 inhibition sensitized pNET cells to radiotherapy and induced apoptosis in vitro. In vivo, we utilized pNET subcutaneous and lung metastasis models to examine the rationale for RNR-targeted therapy and 3-AP as a radiosensitizer in treating pNETs. Combination treatment significantly increased apoptosis of BON (human pNET) xenografts and significantly reduced the burden of lung metastases. Together, our results demonstrate that selective RRM2 inhibition induced radiosensitivity of metastatic pNETs both in vitro and in vivo. Therefore, treatment with the selective RRM2 inhibitor, 3-AP, is a promising radiosensitizer in the therapeutic armamentarium for metastatic pNETs.
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Apoptose , Proliferação de Células , Camundongos Nus , Neoplasias Pancreáticas , Tolerância a Radiação , Radiossensibilizantes , Ribonucleosídeo Difosfato Redutase , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/enzimologia , Ribonucleosídeo Difosfato Redutase/genética , Ribonucleosídeo Difosfato Redutase/antagonistas & inibidores , Ribonucleosídeo Difosfato Redutase/metabolismo , Animais , Linhagem Celular Tumoral , Radiossensibilizantes/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Tolerância a Radiação/efeitos dos fármacos , Fosforilação , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/enzimologia , Tumores Neuroendócrinos/metabolismo , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Transdução de Sinais/efeitos dos fármacos , Quinase 1 do Ponto de Checagem/antagonistas & inibidores , Quinase 1 do Ponto de Checagem/metabolismo , Quinase 1 do Ponto de Checagem/genética , Camundongos , Quinase do Ponto de Checagem 2/metabolismo , Quinase do Ponto de Checagem 2/genética , Quinase do Ponto de Checagem 2/antagonistas & inibidores , Feminino , Interferência de RNA , Proteína Quinase Ativada por DNARESUMO
BACKGROUND: Efficient transfer of adult trauma patients to the intensive care unit (ICU) is associated with decreased emergency department (ED) length of stay (ED LOS) and improved patient outcomes. While well studied in adults, quality improvement (QI) initiatives focused on the rapid transfer of pediatric trauma patients are lacking. We report the effect of institutional system changes directed at expediting the transfer of pediatric trauma patients to the pediatric ICU (PICU). METHODS: This initiative commenced in 2013. Preliminary data regarding ED LOS for pediatric trauma patients were collected from January through December 2012 as the pre-implementation cohort. Using the plan-do-study-act (PDSA) framework of QI, the first PDSA cycle was implemented in January 2013. In subsequent PDSA cycles, we implemented the mandatory attendance of the PICU charge nurse and the PICU attending physician to all highest-level pediatric trauma activations. Throughout, ED LOS was collected and mapped on a run chart. ED LOS and variance were compared between all cycles of implementation. RESULTS: One hundred and fifty-one pediatric patients arrived or were upgraded to the highest-level pediatric trauma activation and admitted to the PICU from 2012 through 2019. We observed a decrease in median ED LOS of 105 minutes between the pre- and post-implementation groups. With each PDSA cycle, we observed a decrease in median ED LOS and variation. CONCLUSION: The inclusion of the PICU charge nurse and attending physician at highest-level pediatric trauma activations facilitated more rapid access to the PICU with decreased ED LOS.
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Transferência de Pacientes , Melhoria de Qualidade , Adulto , Humanos , Criança , Tempo de Internação , Serviço Hospitalar de Emergência , Unidades de Terapia Intensiva Pediátrica , Estudos RetrospectivosRESUMO
Hernia repair mesh aids in the stability of incisional hernia repair and can reduce the need for subsequent operations. There is, however, debate among surgeons over which type of hernia mesh-synthetics, biologics, or biosynthetics-is indicated as best for specific patients. A retrospective case review comparing surgical outcomes based on wound class and mesh materials may provide insights into this question. This study evaluates patient outcomes using biosynthetic mesh based upon CDC wound classification. Following Institutional Review Board approval, the local National Surgery Quality Improvement (NSQIP) databases were queried for open ventral hernia repaired with absorbable mesh implants from January 2013-December 2017. Factors for comparison included patient demographics, operative details, and an analysis of clinical outcomes. Our study identified 112 ventral hernia repair cases with absorbable mesh placement, 32% (n = 36) were wound classes II-IV. Higher wound class correlated statistically with diabetes (33.3%), prior hernia repair (61.1%), and parastomal hernia (44.4%). Higher wound classes were associated with more emergent presentations, involved bowel resection more frequently, required larger mesh implants, increased post-operative surgical site infections, and wound disruption. Increasing wound class was also associated with longer hospital stays and greater need for readmission (38.9% vs. 11.8%). Compared to patients with clean wounds, biosynethic mesh repair patients with contaminated wounds exhibited more emergent presentations, increased incidence of bowel resection, increased mesh size, and more readmissions. Despite these peri-operative outcomes, hernia recurrence rates among biosynethic mesh hernia repair were similar in CDC class II-IV patients as class I.
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Hérnia Ventral , Herniorrafia , Humanos , Herniorrafia/efeitos adversos , Estudos Retrospectivos , Telas Cirúrgicas , Hérnia Ventral/cirurgia , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Resultado do Tratamento , RecidivaRESUMO
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the pediatric and adolescent population, with 350 new cases diagnosed each year. While they can develop anywhere in the body, the genitourinary tract is the second most common primary location for an RMS to develop. Overall survival has improved through the increased use of protocols and multidisciplinary approaches. However, the guidelines for management continue to change as systemic and radiation therapeutics advance. Given the relative rarity of this disease compared to other non-solid childhood malignancies, healthcare providers not directly managing RMS may not be familiar with their presentation and updated management. This review aims to provide foundational knowledge of the management of RMSs with an emphasis on specific management paradigms for those arising from the genitourinary tract. The genitourinary tract is the second most common location for an RMS to develop but varies greatly in symptomology and survival depending on the organ of origin. As the clinical understanding of these tumors advances, treatment paradigms have evolved. Herein, we describe the breadth of presentations for genitourinary RMSs with diagnostic and treatment management considerations, incorporating the most recently available guidelines and societal consensus recommendations.
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This study compares documentation and reimbursement rates before and after provider education in nutritional status documentation. Our study aimed to evaluate accurate documentation of nutrition status between registered dietitian nutritionists and licensed independent practitioners before and after the implementation of a dietitian-led Nutrition-Focused Physical Exam intervention at an academic medical center in the southeastern US. ICD-10 codes identified patients from 10/1/2016-1/31/2018 with malnutrition. The percentage of patients with an appropriate diagnosis of malnutrition and reimbursement outcomes attributed to malnutrition documentation were calculated up to 24 months post-intervention. 528 patients were analyzed. Pre-intervention, 8.64% of patients had accurate documentation compared to 46.3% post-intervention. Post-intervention, 68 encounters coded for malnutrition resulted in an estimated $571,281 of additional reimbursement, sustained at 6, 12, 18, and 24 months. A multidisciplinary intervention improved physician documentation accuracy of malnutrition status and increased reimbursement rates.
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Desnutrição , Nutricionistas , Médicos , Humanos , Melhoria de Qualidade , Desnutrição/diagnóstico , Estado Nutricional , DocumentaçãoRESUMO
BACKGROUND: The focused assessment with sonography in trauma (FAST) is a widely used imaging modality to identify the location of life-threatening hemorrhage in a hemodynamically unstable trauma patient. This study evaluates the role of artificial intelligence in interpretation of the FAST examination abdominal views, as it pertains to adequacy of the view and accuracy of fluid survey positivity. METHODS: Focused assessment with sonography for trauma examination images from 2015 to 2022, from trauma activations, were acquired from a quaternary care level 1 trauma center with more than 3,500 adult trauma evaluations, annually. Images pertaining to the right upper quadrant and left upper quadrant views were obtained and read by a surgeon or radiologist. Positivity was defined as fluid present in the hepatorenal or splenorenal fossa, while adequacy was defined by the presence of both the liver and kidney or the spleen and kidney for the right upper quadrant or left upper quadrant views, respectively. Four convolutional neural network architecture models (DenseNet121, InceptionV3, ResNet50, Vgg11bn) were evaluated. RESULTS: A total of 6,608 images, representing 109 cases were included for analysis within the "adequate" and "positive" data sets. The models relayed 88.7% accuracy, 83.3% sensitivity, and 93.6% specificity for the adequate test cohort, while the positive cohort conferred 98.0% accuracy, 89.6% sensitivity, and 100.0% specificity against similar models. Augmentation improved the accuracy and sensitivity of the positive models to 95.1% accurate and 94.0% sensitive. DenseNet121 demonstrated the best accuracy across tasks. CONCLUSION: Artificial intelligence can detect positivity and adequacy of FAST examinations with 94% and 97% accuracy, aiding in the standardization of care delivery with minimal expert clinician input. Artificial intelligence is a feasible modality to improve patient care imaging interpretation accuracy and should be pursued as a point-of-care clinical decision-making tool. LEVEL OF EVIDENCE: Diagnostic Test/Criteria; Level III.
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Traumatismos Abdominais , Avaliação Sonográfica Focada no Trauma , Ferimentos não Penetrantes , Adulto , Humanos , Inteligência Artificial , Traumatismos Abdominais/diagnóstico por imagem , Ultrassonografia/métodos , Fígado , Sensibilidade e EspecificidadeRESUMO
PURPOSE: All-terrain vehicles (ATVs) pose a significant risk for morbidity and mortality amongst children. We hypothesize that current vague legislation regarding helmet use impacts injury patterns and outcomes in pediatric ATV accidents. METHODS: The institutional trauma registry was queried for pediatric patients involved in ATV accidents from 2006 to 2019. Patient demographics and helmet wearing status were identified in addition to patient outcomes, such as injury pattern, injury severity score, mortality, length of stay, and discharge disposition. These elements were analyzed for statistical significance. RESULTS: 720 patients presented during the study period, which were predominantly male (71%, n = 511) and less than 16 years old (76%, n = 543). Most patients were not wearing a helmet (82%, n = 589) at time of injury. Notably, there were 7 fatalities. A lack of helmet use is positively associated with head injury (42% vs 23%, P < .01), intracranial hemorrhage (15% vs 7%, P = .03), and associated with lower Glasgow Coma Scale (13.9 vs 14.4, P < .01). Children 16 years and older were least likely to wear a helmet and most likely to incur injuries. Patients over 16 years had longer lengths of stay, higher mortality, and higher need for rehabilitation. CONCLUSION: Not wearing a helmet is directly correlated with injury severity and concerning rates of head injury. Children 16 years and older are at greatest risk for injury, but younger children are still at risk. Stricter state laws regarding helmet use are necessary to reduce pediatric ATV-related injury burden. LEVEL OF EVIDENCE: level III retrospective comparative study.
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Traumatismos Craniocerebrais , Veículos Off-Road , Ferimentos e Lesões , Humanos , Criança , Masculino , Adolescente , Feminino , Estudos Retrospectivos , Kentucky/epidemiologia , Acidentes , Traumatismos Craniocerebrais/epidemiologia , Traumatismos Craniocerebrais/etiologia , Traumatismos Craniocerebrais/prevenção & controle , Dispositivos de Proteção da Cabeça , Acidentes de TrânsitoRESUMO
Neuroendocrine neoplasms (NENs) encompass a variety of neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) which can arise anywhere in the body. While relatively rare in the pediatric population, the incidence of NENs has increased in the past few decades. These neoplasms can be devastating if not diagnosed and treated early, however, symptoms are variable and can be indolent for many years. There is a reported median of 10 years from the appearance of the first symptoms to time of diagnosis. Considering some of these neoplasms have a mortality rate as high as 90%, it is crucial healthcare providers are aware of NENs and remain vigilant. With better provider education and easily accessible resources for information about these neoplasms, awareness can be improved leading to earlier disease recognition and diagnosis. This manuscript aims to provide an overview of both the most common NENs as well as the rarer NENs with high lethality in the pediatric population. This review provides up to date evidence and recommendations, encompassing recent changes in classification and advances in treatment modalities, including recently completed and ongoing clinical trials.
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Pediatric cancer patients have improved outcomes over the past several decades leading to a greater number of survivors living well into adulthood. Owing to their increased longevity, adult care providers are encountering childhood cancer survivors with greater frequency in their clinics and hospitals. Childhood cancer treatments are associated with varied and significant systemic complications that either persist or develop well into adulthood, including secondary malignancies, cardiomyopathies, and adhesive disease that can complicate even the simplest operation. This article reviews four of the most common solid abdominal tumors in the pediatric population and the long-term sequelae of their respective treatment regimens.