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OBJECTIVE: to determine diagnostic accuracy of an US-MRI clinical diagnostic pathway to detect appendicitis in the emergency department (ED). STUDY DESIGN: prospective cohort study of 624 previously healthy children 4-17 years old undergoing US for suspected appendicitis and clinical re-assessment. Children with non-diagnostic USs and persistent appendicitis concern/conclusive US-reassessment discrepancies underwent ultra-rapid MRI (US-MRI pathway), interpreted as positive, negative or non-diagnostic. Cases with missed appendicitis, negative appendectomies, and CT utilization were considered clinically diagnostically inaccurate. Primary outcome was the proportion of accurate diagnoses of appendicitis/lack thereof by the pathway. RESULTS: 150/624 (24%) children had appendicitis;255 USs (40.9%) were non-diagnostic. Of 139 US-MRI pathway children (after 117 non-diagnostic and 22 conclusive USs), 137 [98.6%; 95% CI 0.96-1.00] had clinically accurate outcomes (1 CT, 1 negative appendectomy): sensitivity 18/18 [100%], specificity 119/121 [98.3%], positive predictive value 18/20 [90.5%], negative predictive value 119/119 [100%]. MRI imaging accuracy was 134/139 (96.4%); 3 MRIs were non-diagnostic (no appendicitis). In the overall algorithm, 616/624 [98.7% (0.97-0.99)] patients had accurate outcomes: 147/150 (98.0%) appendicitis cases had confirmatory surgeries (3 CTs) and 469/474 (98.9%) appendicitis-negative children had no surgery/CT. CONCLUSION: this study demonstrated high clinical accuracy of the US-rapid-MRI pathway in suspected pediatric appendicitis after non-diagnostic US.
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Apendicite , Criança , Humanos , Pré-Escolar , Adolescente , Estudos Prospectivos , Apendicite/diagnóstico por imagem , Apendicite/cirurgia , Imageamento por Ressonância Magnética/métodos , Apendicectomia , Valor Preditivo dos Testes , Ultrassonografia , Sensibilidade e Especificidade , Estudos RetrospectivosRESUMO
BACKGROUND: Recent advances in hemophilia prophylaxis have raised the need for accurate noninvasive methods for assessment of early cartilage damage in maturing joints to guide initiation of prophylaxis. Such methods can either be semiquantitative or quantitative. Whereas semiquantitative scores are less time-consuming to be performed than quantitative methods, they are prone to subjective interpretation. OBJECTIVE: To test the feasibility of a manual segmentation and a quantitative methodology for cross-sectional evaluation of articular cartilage status in growing ankles of children with blood-induced arthritis, as compared with a semiquantitative scoring system and clinical-radiographic constructs. MATERIALS AND METHODS: Twelve boys, 11 with hemophilia (A, n = 9; B, n = 2) and 1 with von Willebrand disease (median age: 13; range: 6-17), underwent physical examination and MRI at 1.5 T. Two radiologists semiquantitatively scored the MRIs for cartilage pathology (surface erosions, cartilage loss) with blinding to clinical information. An experienced operator applied a validated quantitative 3-D MRI method to determine the percentage area of denuded bone (dAB) and the cartilage thickness (ThCtAB) in the joints' MRIs. Quantitative and semiquantitative MRI methods and clinical-radiographic constructs (Hemophilia Joint Health Score [HJHS], Pettersson radiograph scores) were compared. RESULTS: Moderate correlations were noted between erosions and dAB (r = 0.62, P = 0.03) in the talus but not in the distal tibia (P > 0.05). Whereas substantial to high correlations (r range: 0.70-0.94, P < 0.05) were observed between erosions, cartilage loss, HJHS and Pettersson scores both at the distal tibia and talus levels, moderate/borderline substantial (r range: 0.55-0.61, P < 0.05) correlations were noted between dAB/ThCtAB and clinical-radiographic constructs. CONCLUSION: Whereas the semiquantitative method of assessing cartilage status is closely associated with clinical-radiographic scores in cross-sectional studies of blood-induced arthropathy, quantitative measures provide independent information and are therefore less applicable for that research design.
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Articulação do Tornozelo/fisiologia , Artrite/etiologia , Artrite/patologia , Cartilagem Articular/patologia , Hemofilia A/complicações , Hemofilia A/patologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Algoritmos , Criança , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Reconhecimento Automatizado de Padrão/métodos , Projetos Piloto , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
PURPOSE: While regarded as a secondary sign of pediatric appendicitis, the frequency of physiologic intra-abdominal fluid in children with suspected but absent appendicitis is unknown. Ex vivo: to assess the validity of US/MRI measurements of free fluid. In vivo: in suspected pediatric appendicitis, to assess the amount of abdominal fluid by US and MRI, determine performance characteristics of US in fluid detection and identify fluid volume ranges in confirmed appendicitis. METHODS: Ex vivo: criterion validity of US and MRI for fluid volume measurements was tested using tissue-mimicking phantoms filled with different volumes of distilled water. In vivo: all participants from a previous prospective study of suspected appendicitis were evaluated by US; MRI was performed after equivocal USs. Qualitative and quantitative analyses of abdominal fluid and correlation of fluid presence with appendicitis were performed. RESULTS: Ex vivo: no difference was found between phantom-fluid amount and measured volume using the formula for volume of an ellipsoid for US (P=0.19) or MRI (P=0.08). In vivo: intra-abdominal fluid was present in 212/591 (35.9%) patients; 75/212 patients with fluid (35.4%) had appendicitis, 60 (28.3%) had alternate diagnoses, and 77 (36.3%) had physiologic fluid. Sensitivity and specificity of US for fluid detection were 84% (95% CI 71-93) and 65% (95% CI 52-77), respectively. In children with versus without appendicitis, the respective ranges of fluid volume were 0.7-1148.8 ml and 0.8-318 ml. CONCLUSION: The volume of an ellipsoid formula is a valid method for quantifying intra-abdominal fluid. The sole presence of intra-abdominal fluid on US does not support the diagnosis of pediatric appendicitis.
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Apendicite , Criança , Humanos , Apendicite/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Sensibilidade e Especificidade , Estudos Prospectivos , Ultrassonografia/métodos , Abdome/diagnóstico por imagem , Abdome/patologia , Estudos RetrospectivosRESUMO
OBJECTIVES: Up to 50% of ultrasounds (USs) for suspected pediatric appendicitis are nondiagnostic. While the validated low-risk clinical pediatric Appendicitis Risk Calculator (pARC) score < 15% and the low-risk US with nonvisualized appendix and no periappendiceal inflammation carry relatively low appendicitis risks, the contribution of the combination of both characteristics to this risk has never been assessed. The primary objective was to determine the proportion of children with the low-risk US-low-risk pARC combination with appendicitis. We hypothesized that this proportion would be 2.5% (upper 95% CI ≤ 5%). METHODS: A retrospective cohort study of 448 previously healthy children 4-17 years old at a pediatric ED with suspected appendicitis, nondiagnostic US, and persistent clinical concern about appendicitis. Two investigators abstracted demographic, clinical, and imaging data. Based on published criteria, USs were classified as low-risk or high-risk. The pARC includes seven demographic, clinical, and laboratory variables and is quantified according to the published formula. The primary outcome was appendicitis, based on the histological evidence. All nonoperated patients underwent a 1-month-follow-up to exclude delayed appendicitis diagnoses. RESULTS: Sixty of the 448 (13.4%) patients had appendicitis; 269 (60%) had low-risk US, 262 (58.4%) had low-risk pARC, and 163 (36.4%) had both characteristics. The appendicitis rates with low-risk pARC alone and low-risk US alone were 14/262 (5.4%) and 21/269 (7.8%), respectively. A total of 2/163 children (1.2%) with low-risk pARC and low-risk US had appendicitis (95% CI 0%-4.4%). Higher-risk US increased the appendicitis odds 5 (95% CI 1.54-20.55) to 11 times (95% CI 2.41-51.10) across pARC levels. The low-risk combination had sensitivity of 96.7% (95% CI 88.5%-99.6%), specificity of 41.5%, positive predictive value of 20.4%, and negative predictive value of 98.8% (95% CI 95.6%-99.9%). CONCLUSIONS: The children with low-risk pARC and low-risk US combination are unlikely to have appendicitis and can be discharged home. The presence of higher-risk US-pARC score combinations substantially increases the appendicitis risk and warrants reassessment or interval imaging.
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People with Li-Fraumeni syndrome (LFS) harbor a germline pathogenic variant in the TP53 tumor suppressor gene, face a near 100% lifetime risk of cancer, and routinely undergo intensive surveillance protocols. Liquid biopsy has become an attractive tool for a range of clinical applications, including early cancer detection. Here, we provide a proof-of-principle for a multimodal liquid biopsy assay that integrates a targeted gene panel, shallow whole-genome, and cell-free methylated DNA immunoprecipitation sequencing for the early detection of cancer in a longitudinal cohort of 89 LFS patients. Multimodal analysis increased our detection rate in patients with an active cancer diagnosis over uni-modal analysis and was able to detect cancer-associated signal(s) in carriers prior to diagnosis with conventional screening (positive predictive value = 67.6%, negative predictive value = 96.5%). Although adoption of liquid biopsy into current surveillance will require further clinical validation, this study provides a framework for individuals with LFS. SIGNIFICANCE: By utilizing an integrated cell-free DNA approach, liquid biopsy shows earlier detection of cancer in patients with LFS compared with current clinical surveillance methods such as imaging. Liquid biopsy provides improved accessibility and sensitivity, complementing current clinical surveillance methods to provide better care for these patients. See related commentary by Latham et al., p. 23. This article is featured in Selected Articles from This Issue, p. 5.
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Ácidos Nucleicos Livres , Síndrome de Li-Fraumeni , Humanos , Síndrome de Li-Fraumeni/diagnóstico , Síndrome de Li-Fraumeni/genética , Síndrome de Li-Fraumeni/patologia , Proteína Supressora de Tumor p53/genética , Detecção Precoce de Câncer , Ácidos Nucleicos Livres/genética , Genes p53 , Mutação em Linhagem Germinativa , Predisposição Genética para DoençaRESUMO
Background: In hemophilia, recurrent hemarthrosis may lead to irreversible arthropathy. T2 mapping MRI may reflect cartilage changes at an earlier reversible stage of arthropathy as opposed to structural MRI. Objectives: To evaluate interval changes of T2 mapping compared with the International Prophylaxis Study Group (IPSG) structural MRI scores of ankle cartilage in boys with hemophilia receiving prophylaxis. Methods: Eight boys with hemophilia A (median age, 13; range, 9-17 years), 7 age- and sex-matched healthy boys (controls, median age, 15; range, 7-16 years). A multiecho spin-echo T2-weighted MRI sequence at 3.0T was used to obtain T2 maps of cartilage of boys with hemophilia and controls. Structural joint status was evaluated using the IPSG MRI score. Results: T2 relaxation times of ankle cartilage increased significantly over time in both persons with hemophilia and controls (P = .002 and P = .00009, respectively). Changes in T2 relaxation time strongly correlated with changes in IPSG cartilage scores (rs = 0.93 to rs = 0.78 [P = .0007 to P = .023]), but not with changes in age (P = .304 to P = .840). Responsiveness of T2 relaxation times were higher than that of IPSG cartilage scores, with standardized response means >1.4 for T2 mapping in all regions-of-interest compared with 0.84 for IPSG cartilage scores. Baseline T2 relaxation time strongly correlated with timepoint 2 IPSG cartilage score (rs = 0.93 to rs = 0.82 [P = .001 to P = .012]) and T2 relaxation time (rs = 0.98 to rs = 0.88 [P = .00003 to P = .004]) changes in most regions-of-interest. Conclusion: T2 mapping shows sensitivity to biochemical changes in cartilage prior to detectable damage using conventional MRI, offering potential for early detection of bleed-related cartilage damage in boys with hemophilia.
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OBJECTIVE: To determine predictors of diagnostically inaccurate ultrasound scanning for suspected appendicitis. STUDY DESIGN: Prospective emergency department cohort study of 263 previously healthy children 4 to 17 years of age undergoing ultrasound scanning. Ultrasound scanning results were interpreted as positive, negative, or equivocal for appendicitis and classified as diagnostically accurate and inaccurate. The main outcome measure was association between inaccurate ultrasound scanning and age, sex, body mass index percentiles, pain duration, white blood cell count, Faces Pain Score-Revised, clinical probability of appendicitis, and ultrasound scanning operator. RESULTS: Of the 263 patients, 95 ultrasound scanning examinations were read as positive, 76 as negative, and 92 were equivocal. A total of 162 (61.6%) ultrasound scanning examinations were accurate (TP86, TN76), and 101 (38.4%) ultrasound scanning examinations were inaccurate (FP88, FN13). Children with body mass index percentiles ≥ 85 and clinical probability of appendicitis ≤ 50% had 58.1% probability of inaccurate ultrasound scanning examination (odds ratio, 2.48; 95% confidence interval, 1.48-2.78). In lean children, diagnostic accuracy of the screening ultrasound scanning examination with second ultrasound scanning or clinical reassessment was 93% versus 83% in the obese children (95% confidence interval of the difference, 1-19%). CONCLUSION: Screening ultrasound scanning for pediatric appendicitis has suboptimal accuracy, particularly in obese children with a low likelihood of appendicitis who should not routinely undergo ultrasound scanning. However, when followed by a second ultrasound scanning or a clinical reassessment, it offers high diagnostic accuracy in lean children.
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Apendicite/diagnóstico por imagem , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , UltrassonografiaRESUMO
PURPOSE: 1. To review the contemporary literature and present a list of the imaging findings for patients with autoinflammatory diseases from our hospital. All these patients are found to have a genetic mutation that is responsible for their disease. 2. To present follow-up imaging findings, when available, and correlate those with symptoms and type of treatment administered in approximately 40 patients with autoinflammatory diseases of a single tertiary pediatric health care center including familial Mediterranean fever, Cryopyrin-associated autoinflammatory syndrome, PAPA (pyogenic arthritis, pyoderma gangrenousum, and acne) syndrome, and more. These findings are related to disease progression, treatment response, or treatment-induced changes. CONCLUSION: Autoinflammatory diseases are relatively rare entities that can affect any system of the body. Given the many nonspecific imaging features, awareness of these diseases and good communication with clinicians aid in reaching an accurate diagnosis.
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OBJECTIVES: The primary objective was to determine the diagnostic accuracy of a serial ultrasound (US) clinical diagnostic pathway to detect appendicitis in children presenting to the emergency department (ED). The secondary objective was to examine the diagnostic performance of the initial and interval US and to compare the accuracy of the pathway to that of the initial US. METHODS: This was a prospective cohort study of 294 previously healthy children 4 to 17 years old with suspected appendicitis and baseline pediatric appendicitis scores of ≥2, who were managed with the serial US clinical diagnostic pathway. This pathway consisted of an initial US followed by a clinical reassessment in each patient and an interval US and surgical consultation in patients with equivocal initial US and persistent concern about appendicitis. The USs were interpreted by published criteria as positive, negative, or equivocal for appendicitis. Children in whom this pathway did not rule in or rule out appendicitis underwent computed tomography (CT). Cases with missed appendicitis, negative operations, and CTs after the pathway were considered inaccurate. The primary outcome was the diagnostic accuracy of the serial US clinical diagnostic pathway. The secondary outcomes included the test performance of the initial and interval US imaging studies. RESULTS: Of the 294 study children, 111 (38%) had appendicitis. Using the serial US clinical diagnostic pathway, 274 of 294 children (93%, 95% confidence interval [CI] = 90% to 96%) had diagnostically accurate results: 108 of the 111 (97%) appendicitis cases were successfully identified by the pathway without CT scans (two missed and one CT), and 166 of the 183 (91%) negative cases were ruled out without CT scans (14 negative operations and three CTs). The sensitivity of this pathway was 108 of 111 (97%, 95% CI = 94% to 100%), specificity 166 of 183 (91%, 95% CI = 87% to 95%), positive predictive value 108 of 125 (86%; 95% CI = 79% to 92%), and negative predictive value 166 of 169 (98%, 95% CI = 96% to 100%). The diagnostic accuracy of the pathway was higher than that of the initial US alone (274 of 294 vs. 160 of 294; p < 0.0001). Of 123 patients with equivocal initial US, concern about appendicitis subsided on clinical reassessment in 73 (no surgery and no missed appendicitis). Of 50 children with persistent symptoms, 40 underwent interval US and 10 had surgical consultation alone. The interval US confirmed or ruled out appendicitis in 22 of 40 children (55.0%) with equivocal initial US, with one false-positive interval US. CONCLUSIONS: The serial US clinical diagnostic pathway in suspected appendicitis has an acceptable diagnostic accuracy that is significantly higher than that of the initial US and results in few CT scans. This approach appears most useful in children with equivocal initial US, in whom the majority of negative cases were identified at clinical reassessment and appendicitis was diagnosed by interval US or surgical consultation in most study patients.
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Apendicite/diagnóstico por imagem , Apendicite/diagnóstico , Procedimentos Clínicos , Serviço Hospitalar de Emergência/organização & administração , Doença Aguda , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Exame Físico , Estudos Prospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
BACKGROUND: Obesity constitutes an independent predictor for a nondiagnostic screening ultrasound (US) in suspected appendicitis. Furthermore, the imaging route consisting of the screening US with a second US if necessary has a significantly lower diagnostic accuracy in the obese children (83%) than their lean counterparts (93%). However, the effect of this association on clinical outcomes in the obese population is unknown. OBJECTIVES: In children presenting to the emergency department (ED) undergoing US for suspected appendicitis, the objective was to examine if there is a significant difference in the proportions of those with a "desirable outcome" in the obese group versus their normal-weight counterparts. METHODS: This was a reanalysis of a recent prospective cohort study conducted at a tertiary care pediatric ED. A consecutive sample of 263 previously healthy children 4-17 years of age undergoing screening US for suspected appendicitis was enrolled. Study patients were divided into obese (body mass index-for-age percentiles [BMI-FAP] ≥ 85%) and normal-weight groups. The main outcome was the proportion of children with the desirable outcome in the obese and normal-weight groups. Desirable outcomes for patients with a nondiagnostic screening US were defined as either 1) nonperforated appendicitis or alternate surgical diagnosis undergoing appropriate surgical procedure within 24 hours of assessment without a computed tomography (CT) scan or 2) no appendicitis, discharged from the ED within 24 hours without a CT scan. Secondary outcomes included hospitalization, CT imaging for any reason within 30 days of initial presentation, length of hospital stay, return visits, time to and length of surgery, and complications. RESULTS: Of the 263 patients, 76 (28.9%) were obese, and 187 had a normal weight. Ninety-nine children (37.6%) had appendicitis (obese = 24, normal-weight = 75). The desirable outcome was achieved in 46 (64.5%) of the obese patients versus 137 (73.3%) of the normal-weight children (95% confidence interval [CI] for the difference = -0.21 to 0.04). Compared to the normal-weight children, the obese children had similar hospitalization rates (44.7% vs. 45.5%), median length of hospital stay (20.5 hours vs. 23.0 hours), and return ED visit rates (11.8% vs. 9.1%). The median time to surgery (obese = 10.5 hours, normal-weight = 9.0 hours), complications (obese = 25%, normal-weight = 21.3%), perforations (obese = 33%, normal-weight = 31%), and length of surgery (obese 80 [±37] minutes, normal-weight 67 [±25] minutes) were also similar. The rate of CT within 30 days of initial presentation was higher in the obese compared to the normal-weight group (13/76 or 17.1% vs. 13/187 or 6.9%, 95% CI = 0.02 to 0.23). CONCLUSIONS: Previously healthy obese children undergoing screening US for suspected appendicitis experienced comparable clinical outcomes to their normal-weight counterparts. However, they were three times more likely to receive a CT scan during their investigation. These results argue for continuing current practice of using the screening US in this population, followed by a CT if clinically warranted upon reexamination.
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Apendicite/diagnóstico , Apendicite/terapia , Peso Corporal , Adolescente , Apendicite/diagnóstico por imagem , Apendicite/epidemiologia , Criança , Pré-Escolar , Bases de Dados Factuais , Serviço Hospitalar de Emergência , Feminino , Hospitais Pediátricos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Obesidade/epidemiologia , Estudos Prospectivos , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Resultado do Tratamento , UltrassonografiaRESUMO
El propósito de nuestro estudio fue comparar la reactogenicidad de una vacuna acelular cuando es usada en el primer refuerzo(R1) y en el segundo refuerzo(R2) de la serie DPT.Durante un período de 8 meses se registraron prospectivamente 208 niños.La mitad de ellos recibieron vacuna DPT acelular y la otra mitad,vacuna vacuna DPT celular.A través de un sistema de vigilancia activa se registraron en forma prospectiva las reacciones adversas,locales y sistémicas aparecidas dentro de los siete días posvacunación
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Pré-Escolar , Criança , Adolescente , Vacinas/efeitos adversosRESUMO
El propósito de nuestro estudio fue comparar la reactogenicidad de una vacuna acelular cuando es usada en el primer refuerzo(R1) y en el segundo refuerzo(R2) de la serie DPT.Durante un período de 8 meses se registraron prospectivamente 208 niños.La mitad de ellos recibieron vacuna DPT acelular y la otra mitad,vacuna vacuna DPT celular.A través de un sistema de vigilancia activa se registraron en forma prospectiva las reacciones adversas,locales y sistémicas aparecidas dentro de los siete días posvacunación