Antona, G. (Giuseppa)
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- Flow cytometric characterization of cecal appendix lymphocyte subpopulations in children: a pilot study(Springer, 2023) Ros-Briones, R. (Raquel); Martin-Calvo, N. (Nerea); López, A. (Andrés); Arredondo-Montero, J. (Javier); Hurtado-Ilzarbe, G. (Guillermina); Lopez-Andres, N. (Natalia); Antona, G. (Giuseppa)Introduction: Scientific literature regarding the characterization of lymphocyte subpopulations of the cecal appendix is sparse, with few precedents limited to immunohistochemical techniques. Methods: We conducted a prospective pilot study to characterize lymphocyte subpopulations of the cecal appendix in children. Participants were divided into three groups: (1) patients without histological acute appendiceal inflammation, (2) patients with histological uncomplicated acute appendicitis, and (3) patients with histological complicated acute appendicitis (gangrenous, perforated). A fresh sample of the base of the appendix was taken from all patients and a flow cytometric study was performed. Quantitative variables were compared using Kruskal-Wallis test and Mann-Whitney U test. Results: This study included 57 patients divided into Group 1 (n = 5), Group 2 (n = 37), and Group 3 (n = 15). Median values (IQR) of the percentage of B-lymphocytes were 67.8 [66.8-68.1] in group 1, 61.15 [53.74-66.4] in group 2, and 52.1 [33-62.02] in group 3 (p = 0.02). Median values (IQR) of the percentage of NK-lymphocytes were 0.26 [0.2-0.3] in group 1, 0.55 [0.37-0.66] in group 2, and 0.84 [0.35-1.45] in group 3 (p = 0.008). Median values (IQR) of the percentage of T-lymphocytes were 31.9 [31.7-33.1] in group 1, 37.68 [32.15-45.69] in group 2, and 46.9 [37.03-67] in group 3 (p = 0.02). Pair comparisons of groups 2 and 3 also showed significant differences in the percentage of B lymphocytes (p = 0.03) and NK-lymphocytes (p = 0.02). Conclusions: Significant differences in lymphocyte subpopulations were identified according to the histologic grade of the cecal appendix. More specifically, a lower percentage of B-lymphocytes and a higher percentage of T- and NK-lymphocytes were observed in cases of acute appendicitis. These findings must be confirmed and their etiopathogenic, diagnostic, and prognostic implications elucidated in future studies with larger sample sizes.
- A bilateral whitish lesion on the mucosa of the cheek(Elsevier, 2022) Bronte-Anaut, M. (Mónica); Fernández-Seara, M.P. (María del Pilar); Guarch-Troyas, R. (Rosa); Arredondo-Montero, J. (Javier); Antona, G. (Giuseppa); Ruiz-de-Azúa, Y. (Yerani); Peñafiel-Freire, D.M. (Diego Mauricio)An 8-year-old girl with no medical history presented with a bilateral whitish lesion on the mucosa of the cheek, evident since early childhood. There was no relevant family history, and her parents had not presented similar lesions. They reported a progressive growth of the lesion in the last months, for which she had been evaluated by maxillofacial surgery, the lesion being oriented as a frictional keratosis. However, the use of occlusal splint was not associated with any improvement. She was otherwise asymptomatic. Physical examination revealed a bilateral, whitish, well-demarcated cheek mucosal plaque, which partially coincided with the dental occlusion line. The lesion did not detach with scratching (Figure 1). No other alterations were observed in the oral cavity or in the systematic physical examination.
- Pediatric splenic torsion in an orthotopic spleen without fixation elements(Elsevier, 2022) Bronte-Anaut, M. (Mónica); Ros-Briones, R. (Raquel); Bardají-Pascual, C. (Carlos); Arredondo-Montero, J. (Javier); Moreno-Ibérico, M.A. (Maria Alejandra); Antona, G. (Giuseppa)A 4-year-old girl presented with acute left upper quadrant abdominal pain and anorexia of 4 days’ duration. She had no relevant medical history and no trauma history was reported. Findings of the physical examination showed abdominal guarding and peritoneal irritation in the left upper quadrant. The rest of the examination was normal.
- Diagnostic performance of serum pentraxin-3 in pediatric acute appendicitis: a prospective diagnostic validation study(Springer, 2022) Bronte-Anaut, M. (Mónica); Ros-Briones, R. (Raquel); Martin-Calvo, N. (Nerea); Bardají-Pascual, C. (Carlos); Arredondo-Montero, J. (Javier); Rivero-Marcotegui, A. (Adriana); Fernández-Celís, A. (Amaya); Lopez-Andres, N. (Natalia); Antona, G. (Giuseppa)Introduction Pediatric acute appendicitis (PAA) is a pathology with a high rate of diagnostic error. The search for new diagnostic tools is justified by the high morbidity and healthcare costs associated with diagnostic error. Methods We designed a prospective study to validate serum pentraxin-3 (PTX3) as a diagnostic tool in PAA. Participants were divided into three groups: (1) patients with no underlying pathology (2) patients with non-surgical abdominal pain and (3) patients with a confirmed diagnosis of PAA. For further analyses, patients in group 3 were divided into complicated or uncomplicated PAA. Quantitative variables were expressed as medians and interquartile ranges and categorical variables as percentages. Quantitative variables were compared using the Kruskal–Wallis test and the Mann–Whitney U test. Diagnostic performance was evaluated with ROC curves. Results This study included 215 patients divided into group 1 (n : 63), group 2 (n : 53) and group 3 (n : 99). Median serum PTX3 values were 2.54 (1.70–2.95) ng/mL, 3.29 (2.19–7.64) ng/mL and 8.94 (6.16–14.05) in groups 1, 2 and 3, respectively (p : 0.001). Patients with complicated PAA showed significantly higher values than patients with uncomplicated PAA (p = 0.04). The AUC (group 2 vs. 3) was 0.77 (95/100 CI 0.69–0.85) and the best cut-off point was at 7.28 ng/mL, with a sensitivity of 61.3/100 and a specificity of 73.1/100. The AUC (complicated vs. uncomplicated PAA) was 0.65 (95/100 CI 0.54–0.77) and the best cut-off point was 12.33 ng/mL, with a sensitivity of 51.72/100 and a specificity of 72.73/100. Conclusions The diagnostic ability of serum PTX3 in PAA is only moderate and therefore it cannot be considered a definitive diagnostic test. The discriminatory ability of PTX3 between complicated and uncomplicated PAA is poor. These findings, which contrast with those reported to date, should be validated with future properly designed prospective studies.
- Discriminatory capacity of serum interleukin-6 between complicated and uncomplicated acute appendicitis in children: a prospective validation study(Springer, 2022) Bronte-Anaut, M. (Mónica); Ros-Briones, R. (Raquel); Martin-Calvo, N. (Nerea); Bardají-Pascual, C. (Carlos); Arredondo-Montero, J. (Javier); Rivero-Marcotegui, A. (Adriana); Fernández-Celís, A. (Amaya); Lopez-Andres, N. (Natalia); Antona, G. (Giuseppa)Background: Serum interleukin-6 (IL-6) has a moderate diagnostic performance in pediatric acute appendicitis (PAA). The evidence regarding its capacity to discern between complicated and uncomplicated PAA is scarce. Methods: We designed a prospective observational study to validate serum IL-6 as a marker for diagnostic classification between complicated and uncomplicated PAA. This study included 205 patients divided into three groups: (1) patients who underwent major outpatient surgery (n = 57); (2) patients with non-surgical abdominal pain (NSAP) in whom the diagnosis of PAA was excluded (n = 53), and (3) patients with a confirmed diagnosis of PAA (n = 95). The PAA patients were further classified as uncomplicated or complicated PAA. IL-6 concentration was determined in all patients at diagnosis. Comparative statistical analysis was performed using the Mann-Whitney U test, the Fisher exact test and the Kruskall Wallis test. The area under the receiver operating characteristic curves (AUC) were calculated. Results: Median (interquartile range, IQR) serum IL-6 values were 2 pg/mL (2.0-3.4) in group 1, 3.9 pg/mL (2.4-11.9) in group 2, and 23.9 pg/mL (11.1-61.0) in group 3 (P < 0.001). Among the participants in group 3, those with uncomplicated PAA had median (IQR) serum IL-6 values of 17.2 pg/mL (8.5-36.8), and those with complicated PAA had 60.25 pg/mL (27.1-169) serum IL-6 (P < 0.001). At the cut-off point of 19.55 pg/mL, the AUC for the discrimination between patients in group 2 vs. 3 was 0.83 [95% confidence interval (CI) 0.76-0.90], with a sensitivity of 61.3% and a specificity of 86.8. The AUC for the discrimination between patients with uncomplicated and complicated PAA was 0.77 (95% CI 0.68-0.86) and the cut-off point was 25.90 pg/mL, with a sensitivity and specificity of 84.6% and 65.6%, respectively. Conclusions: Serum IL-6 has a good performance in discerning between complicated and uncomplicated PAA. A score including clinical and radiological variables may increase the diagnostic performance of this molecule.
- Serum neutrophil gelatinase-associated lipocalin (NGAL) as a diagnostic tool in pediatric acute appendicitis: a prospective validation study(Springer, 2022) Bronte-Anaut, M. (Mónica); Ros-Briones, R. (Raquel); Martin-Calvo, N. (Nerea); Bardají-Pascual, C. (Carlos); Arredondo-Montero, J. (Javier); Rivero-Marcotegui, A. (Adriana); Fernández-Celís, A. (Amaya); Lopez-Andres, N. (Natalia); Antona, G. (Giuseppa)Introduction: NGAL has recently been studied as a biomarker in the diagnostic context of pediatric acute appendicitis (PAA), although existing series are scarce and have limited sample sizes. Materials and methods: A prospective observational study was designed to validate serum NGAL as a diagnostic tool in PAA. This study included 215 patients, divided into 3 groups: (1) patients undergoing major outpatient surgery (n: 63), (2) patients with non-surgical abdominal pain in whom a diagnosis of PAA was excluded (n: 53) and (3) patients with a confirmed diagnosis of PAA (n: 99). Patients in group 3 were divided into complicated or uncomplicated appendicitis. In 201 patients, a serum sample was obtained at the time of diagnosis and NGAL concentration was determined by ELISA. The Kolmogorov-Smirnov test was used to assess normality. Comparative statistical analyses were performed using the Mann-Whitney U test, the Kruskal-Wallis test and the Fisher's exact test. To calculate the discriminative ability of the molecule, the area under the receiver-operating characteristic curves (AUC) was calculated. A p value < 0.05 established statistical significance. Results: Median (interquartile range) of serum NGAL values were 38.88 (27.15-48.04) ng/mL (group 1), 51.84 (37.33-69.80) ng/mL (group 2) and 65.06 (50.50-86.60) ng/mL (group 3). The AUC (group 2 vs 3) was 0.642 (95% CI 0.542-0.741) (p < 0.001) and the best cutoff point was found to be at 40.97 ng/mL, with a sensitivity of 89% and a specificity of 34.6%. No statistically significant differences in serum NGAL values were found between patients with uncomplicated PAA and those with complicated PAA. Conclusions: This prospective validation study with a large sample size confirms that the diagnostic yield of NGAL in the context of PAA is only moderate, and therefore, it should not be used as a unique diagnostic tool. Furthermore, NGAL is not a valid biomarker to discern between uncomplicated and complicated PAA.
- Flow cytometric characterization of cecal appendix lymphocyte subpopulations in children: a pilot study(2023) Ros-Briones, R. (Raquel); Martin-Calvo, N. (Nerea); Torres-López, A. (Andrea); Arredondo-Montero, J. (Javier); Hurtado-Ilzarbe, G. (Guillermina); Lopez-Andres, N. (Natalia); Antona, G. (Giuseppa)IntroductionScientific literature regarding the characterization of lymphocyte subpopulations of the cecal appendix is sparse, with few precedents limited to immunohistochemical techniques.MethodsWe conducted a prospective pilot study to characterize lymphocyte subpopulations of the cecal appendix in children. Participants were divided into three groups: (1) patients without histological acute appendiceal inflammation, (2) patients with histological uncomplicated acute appendicitis, and (3) patients with histological complicated acute appendicitis (gangrenous, perforated). A fresh sample of the base of the appendix was taken from all patients and a flow cytometric study was performed. Quantitative variables were compared using Kruskal-Wallis test and Mann-Whitney U test.ResultsThis study included 57 patients divided into Group 1 (n = 5), Group 2 (n = 37), and Group 3 (n = 15). Median values (IQR) of the percentage of B-lymphocytes were 67.8 [66.8-68.1] in group 1, 61.15 [53.74-66.4] in group 2, and 52.1 [33-62.02] in group 3 (p = 0.02). Median values (IQR) of the percentage of NK-lymphocytes were 0.26 [0.2-0.3] in group 1, 0.55 [0.37-0.66] in group 2, and 0.84 [0.35-1.45] in group 3 (p = 0.008). Median values (IQR) of the percentage of T-lymphocytes were 31.9 [31.7-33.1] in group 1, 37.68 [32.15-45.69] in group 2, and 46.9 [37.03-67] in group 3 (p = 0.02). Pair comparisons of groups 2 and 3 also showed significant differences in the percentage of B lymphocytes (p = 0.03) and NK-lymphocytes (p = 0.02).ConclusionsSignificant differences in lymphocyte subpopulations were identified according to the histologic grade of the cecal appendix. More specifically, a lower percentage of B-lymphocytes and a higher percentage of T- and NK-lymphocytes were observed in cases of acute appendicitis. These findings must be confirmed and their etiopathogenic, diagnostic, and prognostic implications elucidated in future studies with larger sample sizes.
- The BIDIAP index: a clinical, analytical and ultrasonographic score for the diagnosis of acute appendicitis in children(Springer, 2023) Ros-Briones, R. (Raquel); Martin-Calvo, N. (Nerea); Bardají-Pascual, C. (Carlos); Arredondo-Montero, J. (Javier); Lopez-Andres, N. (Natalia); Antona, G. (Giuseppa)Background: Pediatric acute appendicitis (PAA) continues to be a diagnostic challenge today. The diagnostic performance of classical indices is only moderate, especially in pediatric population. This study aimed to define a clinical, radiological and analytical index for the diagnosis of PAA. Materials and methods: This prospective study included 151 patients divided into two groups: (1) 53 patients with non-surgical abdominal pain (NSAP) and (2) 98 patients with a confirmed PAA. Sociodemographic and clinical characteristics were compared between groups using the Mann-Whitney U test and the Fisher exact test. To identify the predictors of PAA, we performed a multivariable logistic regression using a forward stepwise analysis and we assigned multiples of integer values to the selected variables. The diagnostic performance of the index was assessed by calculating the area under the receiver operating characteristic curve. Intra-cohort calibration was assessed with the Hosmer-Lemeshow test. Results: We developed the BIDIAP index (BIomarkers for the DIagnosis of Appendicitis in Pediatrics), which included three variables that independently predicted higher odds of PAA: appendiceal caliber (≥ 6.9 mm), systemic immune-inflammation index (≥ 890) and peritoneal irritation, which scored 4, 3 and 2 points, respectively. Mean (SD) score of the participants was 2.38 (2.06) in group 1 and 7.89 (1.50) in group 2. The area under the ROC was 0.97 (95% CI 0.95-0.99). The cut-off point was established at 4 points, resulting in a sensitivity of 98.98% and a specificity of 77.78%. Conclusions: The BIDIAP index has an exceptional diagnostic performance in PAA. The importance of these results lies in its novelty and in the simplicity of the index. Although external validation will be necessary, initial results look promising.
- Alterations and diagnostic performance of capillary ketonemia in pediatric acute appendicitis: a pilot study(Springer, 2022) Bronte-Anaut, M. (Mónica); Martin-Calvo, N. (Nerea); Bardají-Pascual, C. (Carlos); Arredondo-Montero, J. (Javier); Lopez-Andres, N. (Natalia); Antona, G. (Giuseppa)Introduction: The diagnostic performance of capillary ketonemia (CK) has been previously evaluated in context of pediatric acute gastroenteritis. To our knowledge, there is no literature on its performance in the setting of pediatric acute appendicitis (PAA). Materials and methods: In this study, 151 patients were prospectively included and divided into two groups: (1) patients with non-surgical abdominal pain in whom the diagnosis of PAA was excluded (n : 53) and (2) patients with a confirmed diagnosis of PAA (n : 98). In 80 patients (Group 1, n : 23 and group 2, n : 57) a CK was measured at the time of diagnosis. The PAA group was further classified into complicated (n : 18) and uncomplicated PAA (n : 39). Quantitative variables were compared between groups using the Mann-Whitney U test. Diagnostic performance of CK was evaluated with ROC curves. Results: CK values were 0.3 [0.1-0.9] mmol/L in group 1 and 0.7 [0.4-1.4] mmol/L in group 2 (p = 0.01). Regarding the type of PAA, CK values were 0.6 [0.4-0.9] mmol/L in uncomplicated PAA and 1.2 [0.8-1.4] mmol/L in complicated PAA (p : 0.02). The AUC for the discrimination between groups 1 and 2 was 0.68 (95/100 IC 0.53-0.82) (p : 0.24) and the AUC for the discrimination between uncomplicated PAA and complicated PAA was 0.69 (95/100 IC 0.54-0.85) (p : 0.04). The best cut-off point (group 1 vs group 2) resulted in 0.4 mmol/L, with a sensitivity of 80.7/100 and a specificity of 52.2/100. The best cut-off point (non-complicated vs complicated PAA) resulted in 1.1 mmol/L, with a sensitivity of 61.1/100 and a specificity of 76.9/100. Conclusions: This study found significantly higher levels of CK in patients with PAA than in those with NSAP. Similarly, significantly higher levels were observed in patients with complicated than in those with uncomplicated PAA. Nevertheless, the diagnostic performance of CK was only moderate in the two settings analyzed. The potential usefulness of CK determination as a tool to guide the preoperative rehydration regimen of patients with PAA to prevent postoperative hyporexia and vomiting is a promising line of research and should be evaluated in future studies.
- Diagnostic performance of serum interleukin-6 in pediatric acute appendicitis: a systematic review(2022) Arredondo-Montero, J. (Javier); Bardají-Pascual, C. (Carlos); Bronte-Anaut, M. (Mónica); Lopez-Andres, N. (Natalia); Antona, G. (Giuseppa); Martín-Calvo, N. (Nerea)Background Despite the radiological and analytical advances of the last decades, there is still a significant rate of diagnostic error in pediatric acute appendicitis. In recent years, multiple biomarkers have emerged as potential diagnostic tools. This study aimed to examine the diagnostic performance of serum interleukin-6 in pediatric acute appendicitis. Methods We conducted a systematic review of the literature that involved an extensive search in the main databases of medical bibliography (Medline, PubMed, Web of Science and SciELO). Two independent reviewers selected the relevant articles based on the previously defined inclusion and exclusion criteria. Methodological quality of the selected article was rated using the QUADAS2 index. Data extraction was performed by two independent reviewers. Results The research in the medical bibliography databases resulted in 68 articles. We removed 26 duplicates. Among the remaining 42 articles, we excluded 33 following the inclusion and exclusion criteria. Of the final 9 studies included in this review, 8 provided measured serum interleukin-6 values, and all of them reported significant differences between groups, but inconsistent results regarding sensitivity and specificity. Conclusions The diagnostic performance of interleukine-6 alone for the diagnosis of acute appendicitis in children is limited. The sensitivity and specificity of interleukine-6 for the diagnosis of non-complicated acute appendicitis in the pediatric population are moderate but increased in complicated appendicitis. There seems to be a direct relationship between serum level of interleukin-6 and the hours of evolution of abdominal pain in children with acute appendicitis. The increasingly widespread use of non-operative management of acute appendicitis warrants further exploration of the classificatory potential of this marker between complicated and uncomplicated appendicitis. We consider that this may be an avenue of research to explore in the future.