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BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) may be underdiagnosed clinically and radiographically in children with a remote history of cancer, leading to a delay in care and unnecessary lung biopsies. OBJECTIVE: To describe the characteristic clinical and radiologic findings of PPFE in a cohort of children to facilitate recognition and noninvasive diagnosis. MATERIALS AND METHODS: Clinical presentation, history of chemotherapy or radiation therapy, lung or bone marrow transplantation, and lung function testing and outcome were retrospectively extracted from the electronic medical records of eight children treated at our institution's pulmonary medicine clinic with histopathology confirmation of PPFE from 2008 to 2018. Two pediatric radiologists evaluated the chest imaging studies for the presence or absence of published radiologic findings of PPFE in adults, including platythorax, pneumothorax, upper lobe predominant pleural and septal thickening, and bronchiectasis. Platythorax indices were calculated from the normal chest CT exams of eight age- and gender-matched individuals obtained via the radiology search engine. RESULTS: The mean presentation age was 12.9 years (range: 7-16 years). Seven of the eight had a history of chemotherapy and radiation therapy for cancer. Three of the eight had undergone bone marrow transplantation and none had undergone lung transplantation. The mean time between chemotherapy, radiation therapy, and/or bone marrow transplantation and the presentation of PPFE was 8.4 years (range: 5.6-12.1 years). Most of the patients presented with dyspnea (63%), cough (50%) and/or pneumothorax (38%). The mean percentage of predicted FEV1 (forced expiratory volume in one second) was 14.1 (range: 7.7-27.5). All eight patients demonstrated platythorax, bronchiectasis, pleural and septal thickening (upper lobes in four, upper and lower lobes in four) and six had pneumothorax. Five underwent lung biopsies, four of whom developed pneumothoraces. CONCLUSION: Clinical and radiologic findings of pediatric PPFE are similar to those in adults, although a majority of the former have a history of treated cancer. Clinical presentation of restrictive lung disease, dyspnea, cough or spontaneous pneumothorax years after treatment for childhood cancer combined with platythorax, upper lobe pleural and septal thickening and traction bronchiectasis on chest CT establishes a presumptive diagnosis of PPFE.
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Neumonías Intersticiales Idiopáticas/diagnóstico por imagen , Neumonías Intersticiales Idiopáticas/etiología , Tomografía Computarizada por Rayos X , Adolescente , Trasplante de Médula Ósea , Niño , Preescolar , Femenino , Humanos , Neumonías Intersticiales Idiopáticas/fisiopatología , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Pruebas de Función RespiratoriaRESUMEN
Emotional intelligence (EI) is the ability to recognize, understand, and manage emotions in yourself and in others. EI has long been recognized as a critical component for individual and organizational success within the business realm, and there is emerging evidence that enhancing EI is equally important in the medical setting. EI can improve interpersonal communications, enable constructive conflict resolution, and promote a culture of professionalism. As healthcare becomes increasingly team-based, proficiency in EI will be required to build consensus among multidisciplinary stakeholders, and effect change in attitudes and behaviors that result in improved patient safety and clinical outcomes. Based on the existing literature and the authors' experiences, these 12 tips provide practical suggestions on how to introduce EI into a medical curriculum. These tips have broad applicability, and can be implemented in courses on topics such as professionalism, leadership development, empathy, patient safety, or wellness.
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Educación Médica/organización & administración , Inteligencia Emocional , Actitud del Personal de Salud , Retroalimentación Formativa , Procesos de Grupo , Humanos , Grupo de Atención al Paciente/organización & administración , Aprendizaje Basado en Problemas/organización & administración , Autoevaluación (Psicología) , Enseñanza/organización & administraciónRESUMEN
BACKGROUND: Idiopathic membranous nephropathy is an uncommon cause of nephrotic syndrome in children and can present treatment challenges. The current treatment options of steroids and cyclophosphamide, cyclosporine, or mycophenolate require prolonged treatment durations and the associated side effects may result in nonadherence in children, especially in adolescents. CASE-DIAGNOSIS: We report two adolescent patients with idiopathic membranous nephropathy with nephrotic range proteinuria and elevated anti-phospholipase A2 receptor levels who did not achieve remission with steroids and were later treated with rituximab. Both patients received two doses of rituximab and responded with remission. In addition, anti-PLA2R antibody levels normalized and/or significantly improved. CONCLUSIONS: Rituximab seems to be a safe and effective treatment option in children with idiopathic membranous nephropathy due to anti-PLA2R. Further studies are needed to evaluate this effectiveness.
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Glomerulonefritis Membranosa/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Síndrome Nefrótico/tratamiento farmacológico , Rituximab/uso terapéutico , Adolescente , Femenino , Humanos , Riñón/patología , Masculino , Receptores de Fosfolipasa A2/inmunologíaRESUMEN
Infantile myofibromatosis (IM) is the most common benign fibrous tumor of soft tissues affecting young children. By using whole-exome sequencing, RNA sequencing, and targeted sequencing, we investigated germline and tumor DNA in individuals from four distinct families with the familial form of IM and in five simplex IM cases with no previous family history of this disease. We identified a germline mutation c.1681C>T (p.Arg561Cys) in platelet-derived growth factor receptor ß (PDGFRB) in all 11 affected individuals with familial IM, although none of the five individuals with nonfamilial IM had mutations in this gene. We further identified a second heterozygous mutation in PDGFRB in two myofibromas from one of the affected familial cases, indicative of a potential second hit in this gene in the tumor. PDGFR-ß promotes growth of mesenchymal cells, including blood vessels and smooth muscles, which are affected in IM. Our findings indicate p.Arg561Cys substitution in PDGFR-ß as a cause of the dominant form of this disease. They provide a rationale for further investigations of this specific mutation and gene to assess the benefits of targeted therapies against PDGFR-ß in aggressive life-threatening familial forms of the disease.
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Mutación Missense , Miofibromatosis/congénito , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Secuencia de Aminoácidos , Femenino , Genes Dominantes , Estudios de Asociación Genética , Mutación de Línea Germinal , Heterocigoto , Humanos , Masculino , Modelos Moleculares , Miofibromatosis/genética , Linaje , Estructura Terciaria de Proteína , Receptor Notch3 , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/química , Receptores Notch/genética , Análisis de Secuencia de ADNRESUMEN
Inherently defective immunity typically results in either ineffective host defense, immune regulation, or both. As a category of primary immunodeficiency diseases, those that impair immune regulation can lead to autoimmunity and/or autoinflammation. In this review we focus on one of the most recently discovered primary immunodeficiencies that leads to immune dysregulation: "Copa syndrome". Copa syndrome is named for the gene mutated in the disease, which encodes the alpha subunit of the coatomer complex-I that, in aggregate, is devoted to transiting molecular cargo from the Golgi complex to the endoplasmic reticulum (ER). Copa syndrome is autosomal dominant with variable expressivity and results from mutations affecting a narrow amino acid stretch in the COPA gene-encoding COPα protein. Patients with these mutations typically develop arthritis and interstitial lung disease with pulmonary hemorrhage representing a striking feature. Immunologically Copa syndrome is associated with autoantibody development, increased Th17 cells and pro-inflammatory cytokine expression including IL-1ß and IL-6. Insights have also been gained into the underlying mechanism of Copa syndrome, which include excessive ER stress owing to the impaired return of proteins from the Golgi, and presumably resulting aberrant cellular autophagy. As such it represents a novel cellular disorder of intracellular trafficking associated with a specific clinical presentation and phenotype.
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Proteína Coatómero/genética , Síndromes de Inmunodeficiencia , Artritis/genética , Artritis/inmunología , Artritis/patología , Humanos , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/patología , Enfermedades Renales/genética , Enfermedades Renales/inmunología , Enfermedades Renales/patología , Enfermedades Pulmonares/genética , Enfermedades Pulmonares/inmunología , Enfermedades Pulmonares/patologíaRESUMEN
The global COVID-19 pandemic has highlighted the need for rapid, accurate and accessible nucleic acid tests to enable timely identification of infected individuals. We optimized a sample-to-answer nucleic acid test for SARS-CoV-2 that provides results in <1 hour using inexpensive and readily available reagents. The test workflow includes a simple lysis and viral inactivation protocol followed by direct isothermal amplification of viral RNA using RT-LAMP. The assay was validated using two different instruments, a portable isothermal fluorimeter and a standard thermocycler. Results of the RT-LAMP assay were compared to traditional RT-qPCR for nasopharyngeal swabs, nasal swabs, and saliva collected from a cohort of patients hospitalized due to COVID-19. For all three sample types, positive agreement with RT-LAMP performed using the isothermal fluorimeter was 100% for samples with Ct <30 and 69-91% for samples with Ct <40. Following validation, the test was successfully scaled to test the saliva of up to 400 asymptomatic individuals per day as part of the campus surveillance program at Rice University. Successful development, validation, and scaling of this sample-to-answer, extraction-free real-time RT-LAMP test for SARS-CoV-2 adds a highly adaptable tool to efforts to control the COVID-19 pandemic, and can inform test development strategies for future infectious disease threats.
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Prueba de COVID-19 , COVID-19/diagnóstico , Nasofaringe/virología , Nariz/virología , Vigilancia de la Población/métodos , SARS-CoV-2/aislamiento & purificación , Saliva/virología , COVID-19/virología , Humanos , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , ARN Viral/genética , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Distinctions between HHV-6 primary infection in seronegative patients and HHV-6 reactivation in seropositive patients remains largely undescribed in pediatric liver transplant (LT) recipients. METHODS: We implemented pretransplant serology testing of HHV-6 in a large pediatric hospital and retrospectively assessed the incidence, manifestations and outcomes of HHV-6 infections over a 3-year period. RESULTS: Among 101 pediatric LT recipients, 96 had pretransplant HHV-6 serologies; 34 (35.4%) were seronegative and 62 (64.6%) seropositive. Posttransplantation, 8/25 (32%) seronegative patients had HHV-6 DNAemia (primary infection) compared to 2/48 (4%) seropositive patients (p=0.002). Compared to seropositive patients, seronegative patients with HHV-6 DNAemia were younger, and had symptoms of fever and/or elevated aminotransferases in association with higher viral loads, in the first month post-transplant. More than 90% of seronegative patients and 77.8% of seropositive patients had HHV-6 detected by PCR in liver biopsy obtained for concerns of allograft rejection, but most had no detectable concomitant DNAemia. Active replication of virus in the liver was confirmed by in situ hybridization in select cases. While HHV-6 infection occurred among patients on prophylaxis doses of antivirals for CMV, HHV-6 DNAemia and presenting symptoms resolved on treatment doses. CONCLUSIONS: HHV-6 DNA-emia occurred more frequently in seronegative pediatric LT recipients, usually in the early posttransplant period, and was subsequently detected in allograft biopsies. HHV-6 cannot be ruled out as a cause of hepatitis in the absence of allograft tissue testing and specialized virological assays, as HHV-6 may disrupt local allograft immune homeostasis while evading traditional screening methods using blood or plasma. The assessment of pre-transplant HHV-6 serological status may be important for risk stratification and post-transplant management of pediatric LT recipients.
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Herpesvirus Humano 6 , Trasplante de Hígado , Niño , ADN Viral , Femenino , Humanos , Incidencia , Estudios RetrospectivosRESUMEN
Immunoglobulin (Ig) M nephropathy is defined by electron-dense mesangial deposits and mesangial IgM visible by immunofluorescence (IF) without other histopathologic and immunofluorescent microscopic abnormalities. Certain patients have only immuno-positive (IgM+) IF. Children presenting with steroid-dependent or steroid-resistant nephrotic syndrome have a high prevalence of IgM+ IF with or without electron-dense deposits. We reviewed the clinical course of children with steroid-dependent or steroid-resistant nephrotic syndrome who underwent renal biopsy at Texas Children's Hospital from 1989 to 2006 to further characterize IgM+ IF in children with nephrotic syndrome. Of the 55 children with steroid-resistant or -dependent minimal change disease (MCD), 23 had IgM+ IF. Of these 23 children, 61% had microscopic hematuria at presentation, 48% (11/23) were steroid-dependent, and 48% (11/23) steroid-resistant (one underwent biopsy prior to steroid therapy). We compared the efficacy of adjuvant treatment with cyclophosphamide and cyclosporine: 18% initially treated with cyclophosphamide obtained remission, while 55% had no response; 83% obtained subsequent remission with cyclosporine. Of those initially treated with cyclosporine, 88% obtained complete or partial remission. IgM+ IF may be surrogate marker for the severity of MCD. Based on our results, children with MCD and IgM+ IF have a better response to cyclosporine than cyclophosphamide.
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Inmunoglobulina M/análisis , Nefrosis Lipoidea/patología , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/inmunología , Síndrome Nefrótico/patología , Biopsia , Quimioterapia Adyuvante , Niño , Preescolar , Estudios de Cohortes , Ciclofosfamida/uso terapéutico , Ciclosporina/uso terapéutico , Femenino , Técnica del Anticuerpo Fluorescente , Mesangio Glomerular/inmunología , Mesangio Glomerular/patología , Humanos , Inmunosupresores/uso terapéutico , Riñón/cirugía , Masculino , Nefrosis Lipoidea/tratamiento farmacológico , Síndrome Nefrótico/tratamiento farmacológico , Estudios Retrospectivos , Prevención Secundaria , Resultado del TratamientoRESUMEN
In the past pyogenic granuloma (PG) in infancy has been easily confused clinically and histopathologically with infantile hemangioma (IH). In 2000 North and colleagues discovered that IH is immunopositive for GLUT-1, a glucose transporter which is also expressed in placental capillaries (1). GLUT-1 staining is negative in pyogenic granuloma. We report two newborns with congenital disseminated PG who were otherwise healthy. In both of these cases, negative GLUT-1 staining supported the proper diagnosis.
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Granuloma Piogénico/congénito , Femenino , Granuloma Piogénico/patología , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
Childhood-onset systemic lupus erythematosus (SLE) is a subset of SLE with an onset before 18 years of age. Patients with early onset SLE tend to have a greater genetic component to their disease cause, more multisystemic involvement, and a more severe disease course, which includes greater risks for developing nephritis and end-stage kidney disease. Five- and 10-year mortality is lower than in adult-onset SLE. Although patient and renal survival have improved with advances in induction and maintenance immunosuppression, accumulation of irreversible damage is common. Cardiovascular and infectious complications are frequent, as are relapses during adolescence and the transition to adulthood.
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Corticoesteroides/uso terapéutico , Inmunosupresores/uso terapéutico , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/tratamiento farmacológico , Biopsia , Niño , Diagnóstico Diferencial , Humanos , Nefritis Lúpica/patologíaRESUMEN
BACKGROUND: BK virus (BKV), JC virus (JCV) and simian virus 40 (SV40) are nonenveloped DNA viruses, members of the family Polyomaviridae. BK and JC viruses establish persistent infections in humans, and evidence suggests that SV40 can infect humans, as well. Whether persistence occurs in the lymphoid system is unknown. METHODS: Paraffin-embedded tonsils from 220 immunocompetent children (mean age 9.3 years) were examined by polymerase chain reaction (PCR) to detect viral DNA of BKV, JCV, SV40, and Epstein-Barr virus (EBV). RESULTS: Polyomavirus-specific DNA sequences were detected in 8.3% (29/351) of specimens collected from 220 children. Twenty-one (9.5%) children had polyomavirus DNA present in at least one tonsil, with sequences identified as SV40 (n=20) and BKV (n=1). Polyomavirus JCV was not detected. Among patients positive for SV40, 8 of 14 (57%) contained viral DNA in both available tonsils. EBV DNA was detected in 99 (28.2%) samples from 67 (30.5%) patients. Eleven samples (3.1%) from 8 (3.6%) children were positive for both polyomavirus and EBV. SV40-positive children were significantly older than the SV40-negative subjects (P<0.001). T-antigen expression was detected in an SV40 DNA-positive tonsil by immunohistochemistry. CONCLUSIONS: These results suggest that SV40 can infect tonsils, that lymphoid tissue may represent a site for polyomavirus persistence, and that immunohistochemistry is not a useful detection assay when there are very few virus-infected cells in a tissue.
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Tonsila Palatina/virología , Enfermedades Faríngeas/diagnóstico , Infecciones por Polyomavirus/diagnóstico , Virus 40 de los Simios/aislamiento & purificación , Infecciones Tumorales por Virus/diagnóstico , Adolescente , Antígenos Transformadores de Poliomavirus/genética , Antígenos Transformadores de Poliomavirus/aislamiento & purificación , Niño , Preescolar , Femenino , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Inmunocompetencia , Masculino , Tonsila Palatina/patología , Enfermedades Faríngeas/virología , Reacción en Cadena de la Polimerasa , Infecciones por Polyomavirus/virología , Virus 40 de los Simios/genéticaRESUMEN
Papillary fibroelastomas are benign primary cardiac tumors that usually arise from the valve apparatus and are rare in the pediatric population. Involvement of the tricuspid valve is even less common with only a few cases reported in the literature. Cardiac magnetic resonance imaging is a valuable examination that aids in differentiating a tumor from a thrombus. We present the case of an 11-month-old girl referred by her pediatrician to investigate a murmur noted since birth. To our knowledge, this is the first report of a pathologically proven papillary fibroelastoma arising from the tricuspid valve characterized by magnetic resonance imaging in an infant.
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STUDY OBJECTIVE: To report on the clinical characteristics and outcome of pediatric patients with juvenile granulosa cell tumor (JGCT) of the ovary. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Patients with histopathologically confirmed ovarian JGCT diagnosed between 1990 and 2016 were identified. Data on the clinical presentation, surgical management, oncologic management, laboratory investigation, follow-up, and outcome were collected. Tumors were staged according to the International Federation of Gynecology and Obstetrics criteria. RESULTS: Eight patients were diagnosed with ovarian JGCT during the study period. The median age at presentation was 3 years (range, 0.7-14 years). Precocious puberty was the presenting symptom in all five prepubertal children; abdominal distension due to mass effect was the presenting symptom in three children older than 9 years of age. In patients who had preoperative serologic testing, estradiol (n = 3) and inhibin (n = 3) levels were elevated. Five patients had stage I disease, and three had stage III. All stage I patients underwent salpingo-oophorectomy as the only treatment. Stage III patients received adjuvant chemotherapy. After a median follow-up of 6.2 years, six patients (75%) were alive without evidence of disease. One stage I patient with germline p53 mutation and phosphatase and tensin homolog mutation, died because of subsequent liposarcoma. One patient with stage IIIB disease developed recurrence detected according to an elevated inhibin serum level, and died due to progressive disease despite receiving multiple chemotherapy regimens. CONCLUSION: Juvenile granulosa cell tumor has a favorable prognosis in patients with stage I disease after surgical resection alone. Adjuvant chemotherapy might be indicated in patients with higher-stage tumors.
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Tumor de Células de la Granulosa/patología , Neoplasias Ováricas/patología , Adolescente , Quimioterapia Adyuvante , Niño , Preescolar , Femenino , Tumor de Células de la Granulosa/complicaciones , Tumor de Células de la Granulosa/terapia , Humanos , Lactante , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/terapia , Ovariectomía/métodos , Pronóstico , Pubertad Precoz/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Carga TumoralAsunto(s)
Proteína Coatómero/genética , Disnea/etiología , Hematuria/etiología , Enfermedades Renales/genética , Enfermedades Pulmonares/genética , Adolescente , Diagnóstico Diferencial , Disnea/diagnóstico por imagen , Femenino , Hematuria/diagnóstico por imagen , Humanos , Enfermedades Renales/diagnóstico por imagen , Enfermedades Pulmonares/diagnóstico por imagen , SíndromeRESUMEN
IMPORTANCE: Whole-exome sequencing (WES) has the potential to reveal tumor and germline mutations of clinical relevance, but the diagnostic yield for pediatric patients with solid tumors is unknown. OBJECTIVE: To characterize the diagnostic yield of combined tumor and germline WES for children with solid tumors. DESIGN: Unselected children with newly diagnosed and previously untreated central nervous system (CNS) and non-CNS solid tumors were prospectively enrolled in the BASIC3 study at a large academic children's hospital during a 23-month period from August 2012 through June 2014. Blood and tumor samples underwent WES in a certified clinical laboratory with genetic results categorized on the basis of perceived clinical relevance and entered in the electronic health record. MAIN OUTCOMES AND MEASURES: Clinical categorization of somatic mutations; frequencies of deleterious germline mutations related to patient phenotype and incidental medically-actionable mutations. RESULTS: Of the first 150 participants (80 boys and 70 girls, mean age, 7.4 years), tumor samples adequate for WES were available from 121 patients (81%). Somatic mutations of established clinical utility (category I) were reported in 4 (3%) of 121 patients, with mutations of potential utility (category II) detected in an additional 29 (24%) of 121 patients. CTNNB1 was the gene most frequently mutated, with recurrent mutations in KIT, TSC2, and MAPK pathway genes (BRAF, KRAS, and NRAS) also identified. Mutations in consensus cancer genes (category III) were found in an additional 24 (20%) of 121 tumors. Fewer than half of somatic mutations identified were in genes known to be recurrently mutated in the tumor type tested. Diagnostic germline findings related to patient phenotype were discovered in 15 (10%) of 150 cases: 13 pathogenic or likely pathogenic dominant mutations in adult and pediatric cancer susceptibility genes (including 2 each in TP53, VHL, and BRCA1), 1 recessive liver disorder with hepatocellular carcinoma (TJP2), and 1 renal diagnosis (CLCN5). Incidental findings were reported in 8 (5%) of 150 patients. Most patients harbored germline uncertain variants in cancer genes (98%), pharmacogenetic variants (89%), and recessive carrier mutations (85%). CONCLUSIONS AND RELEVANCE: Tumor and germline WES revealed mutations in a broad spectrum of genes previously implicated in both adult and pediatric cancers. Combined reporting of tumor and germline WES identified diagnostic and/or potentially actionable findings in nearly 40% of newly diagnosed pediatric patients with solid tumors.
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We present the case of a 13-year-old immunosuppressed patient with unrelenting cat scratch disease despite 9 months of antibiotic therapy. The patient was being treated with mycophenolate and prednisone for membranoproliferative glomerulonephritis (type 1) diagnosed 13 months before the onset of cat scratch disease. Cat scratch disease was suspected due to epitrochlear lymphadenitis and an inoculation papule on the ipsilateral thumb, and the diagnosis was confirmed by the use of acute and convalescent titers positive for Bartonella henselae. The patient experienced prolonged lymphadenitis despite azithromycin and rifampin therapy, and she developed a draining sinus tract â¼4 months after initial inoculation while receiving antibiotics. Acute exacerbation of the primary supratrochlear node prompted incision and drainage of the area, with no improvement in the disease course. Ultimately, excision of all affected nodes and the sinus tract 9 months after the initial diagnosis was required to achieve resolution. Bartonella was detected at a high level according to a polymerase chain reaction assay in the excised nodes. Persistent treatment with oral antibiotics may have prevented disseminated infection in this immunosuppressed patient. Surgical excision of affected nodes should be considered in patients with cat scratch disease that persists beyond 16 weeks.
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Enfermedad por Rasguño de Gato/cirugía , Adolescente , Antibacterianos/uso terapéutico , Enfermedad por Rasguño de Gato/complicaciones , Enfermedad por Rasguño de Gato/tratamiento farmacológico , Femenino , Glomerulonefritis Membranoproliferativa/complicaciones , Humanos , Insuficiencia del TratamientoRESUMEN
BACKGROUND: The stratification of appendicitis into simple and complex variants has far-reaching implications. While the operative diagnosis made by the surgeon dictates clinical management, the pathologic diagnosis often differs and is frequently used for coding and reimbursement. The purpose of this study was to examine discrepancies between the operative and pathologic diagnoses with subsequent correlation to clinical outcomes. METHODS: Patients with acute appendicitis from July 2011 to July 2012 were identified. Diagnoses included simple (normal, acute, and suppurative) and complex (gangrenous and perforated). We evaluated the inter-rater reliability between pathologic and operative diagnoses in the five appendicitis categories. Clinical outcomes of deep and superficial surgical site infections were evaluated according to the pathologic and surgical diagnosis. RESULTS: During the study period, we identified 1166 patients with acute appendicitis. The surgeon and pathologist agreed on the specific diagnosis (acute, suppurative, gangrenous, perforated, normal) in 48% of patients (kappa 0.289, 95% CI 0.259-0.324, p=0.001). Agreement on disease severity (simple vs. complex) improved to 82%. The operative diagnosis more accurately predicted infectious complications than the pathologic diagnoses. CONCLUSION: Significant discordance exists between surgical and pathologic diagnoses. While the relevance of this discordance to clinical outcomes is still not clear, a potential for incorrect hospital coding and subsequent reimbursement exists. Future quality improvement projects should focus on standardizing the surgical and pathologic diagnoses.
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Apendicectomía , Apendicitis/diagnóstico , Enfermedad Aguda , Adolescente , Apendicitis/cirugía , Niño , Diagnóstico Diferencial , Femenino , Humanos , Lactante , Masculino , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
The X-linked BCL-6 co-repressor (BCOR) gene encodes a key constituent of a variant polycomb repressive complex (PRC) that is mutated or translocated in human cancers. Here we report on the identification of somatic internal tandem duplications (ITDs) clustering in the C terminus of BCOR in 23 of 27 (85%) pediatric clear cell sarcomas of the kidney (CCSK) from two independent cohorts. We profile CCSK tumours using a combination of whole-exome, transcriptome and targeted sequencing. Identical ITD mutations are found in primary and relapsed tumour pairs but not in adjacent normal kidney or blood. Mutant BCOR transcripts and proteins are markedly upregulated in ITD-positive tumours. Transcriptome analysis of ITD-positive CCSKs reveals enrichment for PRC2-regulated genes and similarity to undifferentiated sarcomas harbouring BCOR-CCNB3 fusions. The discovery of recurrent BCOR ITDs defines a major oncogenic event in this childhood sarcoma with significant implications for diagnostic and therapeutic approaches to this tumour.