Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment.

BACKGROUND/AIMS: Changes in gene expression profiles among individuals with inflammatory bowel diseases (IBDs) could potentially influence the responsiveness to anti-TNF treatment. The aim of this study was to identify genes that could serve as predictors of early response to anti-TNF therapies in pediatric IBD patients prior to the initiation of treatment. METHODS: We conducted a prospective, longitudinal, and multicenter study, enrolling 24 pediatric IBD patients aged less than 18 years who were initiating treatment with either infliximab or adalimumab. RNA-seq from blood samples was analyzed using the DESeq2 library by comparing responders and non-responders to anti-TNF drugs. RESULTS: Bioinformatic analyses unveiled 102 differentially expressed genes, with 99 genes exhibiting higher expression in responders compared to non-responders prior to the initiation of anti-TNF therapy. Functional enrichment analyses highlighted defense response to Gram-negative bacteria (FDR = 2.3 ×10-7) as the most significant biological processes, and hemoglobin binding (FDR = 0.002), as the most significant molecular function. Gene Set Enrichment Analysis (GSEA) revealed notable enrichment in transcriptional misregulation in cancer (FDR = 0.016). Notably, 13 genes (CEACAM8, CEACAM6, CILP2, COL17A1, OLFM4, INHBA, LCN2, LTF, MMP8, DEFA4, PRTN3, AZU1, and ELANE) were selected for validation, and a consistent trend of increased expression in responders prior to drug administration was observed for most of these genes, with findings for 4 of them being statistically significant (CEACAM8, LCN2, LTF2, and PRTN3). CONCLUSIONS: We identified 102 differentially expressed genes involved in the response to anti-TNF drugs in children with IBDs and validated CEACAM8, LCN2, LTF2, and PRTN3. Genes participating in defense response to Gram-negative bacterium, serine-type endopeptidase activity, and transcriptional misregulation in cancer are good candidates for anticipating the response to anti-TNF drugs in children with IBDs.

Benefits of Paediatric to Adult Transition Programme in Inflammatory Bowel Disease: The BUTTERFLY Study of GETECCU and SEGHNP.

(1) Background: Transition is a planned movement of paediatric patients to adult healthcare systems, and its implementation is not yet established in all inflammatory bowel disease (IBD) units. The aim of the study was to evaluate the impact of transition on IBD outcomes. (2) Methods: Multicentre, retrospective and observational study of IBD paediatric patients transferred to an adult IBD unit between 2017-2020. Two groups were compared: transition (≥1 joint visit involving the gastroenterologist, the paediatrician, a programme coordinator, the parents and the patient) and no-transition. Outcomes within one year after transfer were analysed. The main variable was poor clinical outcome (IBD flare, hospitalisation, surgery or any change in the treatment because of a flare). Predictive factors of poor clinical outcome were identified with multivariable analysis. (3) Results: A total of 278 patients from 34 Spanish hospitals were included. One hundred eighty-five patients (67%) from twenty-two hospitals (65%) performed a structured transition. Eighty-nine patients had poor clinical outcome at one year after transfer: 27% in the transition and 43% in the no-transition group (p = 0.005). One year after transfer, no-transition patients were more likely to have a flare (36% vs. 22%; p = 0.018) and reported more hospitalisations (10% vs. 3%; p = 0.025). The lack of transition, as well as parameters at transfer, including IBD activity, body mass index < 18.5 and corticosteroid treatment, were associated with poor clinical outcome. One patient in the transition group (0.4%) was lost to follow-up. (4) Conclusion: Transition care programmes improve patients' outcomes after the transfer from paediatric to adult IBD units. Active IBD at transfer impairs outcomes.

Polymorphisms indicating risk of inflammatory bowel disease or antigenicity to anti-TNF drugs as biomarkers of response in children.

Few genetic polymorphisms predict early response to anti-TNF drugs in inflammatory bowel disease (IBD), and even fewer have been identified in the pediatric population. However, it would be of considerable clinical interest to identify and validate genetic biomarkers of long-term response. Therefore, the aim of the study was to analyze the usefulness of biomarkers of response to anti-TNFs in pediatric IBD (pIBD) as long-term biomarkers and to find differences by type of IBD and type of anti-TNF drug. The study population comprised 340 children diagnosed with IBD who were treated with infliximab or adalimumab. Genotyping of 9 selected SNPs for their association with early response and/or immunogenicity to anti-TNFs was performed using real-time PCR. Variants C rs10508884 (CXCL12), A rs2241880 (ATG16L1), and T rs6100556 (PHACTR3) (p value 0.049; p value 0.03; p value 0.031) were associated with worse long-term response to anti-TNFs in pIBD. DNA variants specific to disease type and anti-TNF type were identified in the pediatric population. Genotyping of these genetic variants before initiation of anti-TNFs would enable, if validated in a prospective cohort, the identification of pediatric patients who are long-term responders to this therapy.

Association between HLA DNA Variants and Long-Term Response to Anti-TNF Drugs in a Spanish Pediatric Inflammatory Bowel Disease Cohort.

The genetic polymorphisms rs2395185 and rs2097432 in HLA genes have been associated with the response to anti-TNF treatment in inflammatory bowel disease (IBD). The aim was to analyze the association between these variants and the long-term response to anti-TNF drugs in pediatric IBD. We performed an observational, multicenter, ambispective study in which we selected 340 IBD patients under 18 years of age diagnosed with IBD and treated with anti-TNF drugs from a network of Spanish hospitals. Genotypes and failure of anti-TNF drugs were analyzed using Kaplan-Meier curves and Cox logistic regression. The homozygous G allele of rs2395185 and the C allele of rs2097432 were associated with impaired long-term response to anti-TNF drugs in children with IBD after 3 and 9 years of follow-up. Being a carrier of both polymorphisms increased the risk of anti-TNF failure. The SNP rs2395185 but not rs2097432 was associated with response to infliximab in adults with CD treated with infliximab but not in children after 3 or 9 years of follow-up. Conclusions: SNPs rs2395185 and rs2097432 were associated with a long-term response to anti-TNFs in IBD in Spanish children. Differences between adults and children were observed in patients diagnosed with CD and treated with infliximab.

Endoscopic stapes surgery outcomes and complication rates: a systematic review.

OBJECTIVE: These days, the gold standard procedure for otosclerosis treatment is stapes surgery. The endoscopic approach of the procedure is gaining popularity as endoscopic ear surgery develops across the globe. The main objective of this study is to gather and compile well-documented and reliable data regarding surgical outcomes for the endoscopic approach to stapes surgery up to this date. MATERIALS AND METHODS: Publications in English were searched in the PUBMED/MEDLINE database and were systematically reviewed. A total of 16 articles were reviewed according to the inclusion criteria, obtaining a total of 573 patients managed surgically for otosclerosis, using an endoscopic approach. Data were systematically extracted and compared across variables. RESULTS: Data were obtained as follows: mean age of 43 years; female proportion of 60%; 3 mm endoscope diameter of 51%, 4 mm of 39%; titanium piston-type prostheses of 52% and Teflon of 48%; length of the prosthesis (mode) was 4.5 mm; 0.6 mm diameter of the piston of 81% and 0.4 mm of 19%; mean surgical time was 55 min. Hearing results, mean preoperative air-bone gap (ABG) 31 dB; mean postoperative ABG 9 dB; ABG improvement of 22 dB; an ABG closure rate to 20 dB or less of 92% and an ABG closure rate to 10 dB or less of 77%. Complication rates: intraoperative tympanic membrane perforation of 5%; postoperative vertigo of 11%; postoperative dysgeusia of 10%; reported a postoperative neurosensorial hearing loss of 0.2%; reported gusher phenomenon of one case (0.2%). CONCLUSION: Endoscopic stapes surgery is completely achievable using 0º angle and 4-mm-diameter sinus surgery endoscope. Instrument availability should not be an obstacle to the development of this type of surgery in any otolaryngology department. Audiological outcomes are comparable to microscopic approaches.

[Applicability of 3/4D transperineal ultrasound for the diagnosis of anal sphincter injury during the immediate pospartum]. / Aplicabilidad de la ecografía transperineal en 3/4D para el diagnóstico de lesiones del esfínter anal durante el posparto inmediato.

BACKGROUND: The most common cause of anal sphincter injuries in women is vaginal birth. Endo-anal ultrasound is currently used for the diagnosis of anal sphincter defect. However, due to the inconvenience caused, it is not an applicable technique during the immediate post-partum. The aim of this study was to determine whether transperineal ultrasound in 3/4D is a useful diagnostic method for the assessment of anal sphincter during the immediate post-partum. MATERIAL AND METHODS: A prospective study was conducted on the vaginal deliveries performed between September 2012 and June 2013 in the Valme University Hospital (Seville). Obstetric and foetal parameters that could influence the onset of perineal tears were studied. The patients underwent a transperineal 3/4D ultrasound and a multislice study (48hours after birth). RESULTS: The study included 146 puerperal women. The sphincter complex was assessed in all of them during the immediate post-partum. External anal injuries were observed in 10.3% of the cases. In 8.2% of cases, the primary suture of the external anal sphincter was detected during ultrasound examination, and 2.1% of asymptomatic lesions were diagnosed only with post-partum ultrasound. None of the patients reported discomfort or pain. CONCLUSIONS: The 3-dimensional transperineal ultrasound is helpful in determining the primary repair of the anal sphincter during the immediate post-partum, with no discomfort for patients, as well as for establishing those early sphincter injuries that go unnoticed during vaginal delivery.

[Triple synchronous primary gynaecological tumours. A case report]. / Tumores triple sincrónicos ginecológicos. Reporte de un caso.

BACKGROUND: Synchronous multiple primary malignancies in the female genital tract are infrequent. From 50 to 70% of them corresponds to synchronous cancers of the endometrium and ovary. To our knowledge, this is only the third case report in the international literature of three concurrent gynaecological cancers of epithelial origin. A case is presented, as well as a literature review due to the infrequency of its diagnosis and the lack of information on the subject. CLINICAL CASE: A 49-year-old woman, with previous gynaecological history of ovarian endometriosis. She underwent a hysterectomy and bilateral oophorectomy, as she had been diagnosed with endometrial hyperplasia with atypia. The final histopathology reported synchronous ovarian, Fallopian tube, and endometrial cancer. An extension study and complete surgical staging was performed, both being negative. She received adjuvant treatment of chemotherapy and radiotherapy. She is currently free of disease. CONCLUSIONS: The aetiology is uncertain. There is controversy relating to increased susceptibility of synchronous neoplasms to pelvic endometriosis and inherited genetic syndromes. Its diagnosis needs to differentiate them from metastatic disease. Additionally, they are problematical from a clinical, diagnostic, therapeutic, and prognostic point of view. The presentation of more cases of triple synchronous cancers is necessary for a complete adjuvant and surgical treatment.

Factors that influence the development of avulsion of the levator ani muscle in eutocic deliveries: 3-4D transperineal ultrasound study.

INTRODUCTION: Levator ani muscle (LAM) lesions are the most frequent injuries of the pelvic floor during delivery. Ten to 36% of women report this lesion during their first delivery. Many risk factors have been proposed but very few evaluate the aspects that can influence during natural vaginal delivery. METHOD: A prospective observational trial was conducted involving 74 primiparous women following vaginal delivery. Maternal, fetal and obstetric characteristics were analyzed. A transperineal three or four-dimensional (3D-4D) ultrasound was offered six months after delivery in order to evaluate avulsions and anomalies of the hiatus. RESULTS: Seventy four women were included, three of them did not show up for ultrasound evaluation. Sixty two (87.3%) demonstrated no avulsion in comparison with nine (12.7%) who did. Five of these lesions were unilateral and four bilateral. Mean newborn weight was 3193 g in the "no avulsion group" versus 3470 g in the "avulsion" group (p=0.025). DISCUSSION: According to the results, the most important risk factor established, for avulsion during natural childbirth, was the newborn weight. This contrasts with many other authors who have established that birth weight has no impact on these lesions. CONCLUSIONS: The most important factor intervening in the avulsion of LAM during natural vaginal delivery is the newborn weight. Patients with diagnosed avulsions present an enlarged urogenital hiatus during valsalva and maximal contraction.

[Synchronous bilateral breast cancer in a male]. / Carcinoma mamario bilateral sincrónico en un varón.

BACKGROUND: male breast cancer is a disease with low incidence, which is further reduced when it comes to bilateral synchronous presentation. There are few published cases in recent years. The aim is to establish guidelines for the management of this disorder that is so rare. CLINICAL CASE: a 75-year-old with tumors in both breasts, which were completely resected with removal of palpable nodes. The histopathological study reported ductal carcinoma. The indicated treatment was adjuvant tamoxifen and radiotherapy. The patient is currently in a disease-free period. CONCLUSIONS: this is a rare disease, whose main treatment is surgery, hence the importance of early diagnosis. Most cases require adjuvant chemotherapy and radiotherapy because they are usually diagnosed at an advanced stage.

antecedentes: el cáncer de mama en el hombre es una enfermedad con baja incidencia, que se reduce aún más cuando es bilateral sincrónica. Existen pocas publicaciones en los últimos años. Objetivo: establecer pautas para el tratamiento de este cáncer, aunque sea infrecuente. Caso clínico: paciente masculino de 75 años de edad, con tumores en ambas mamas, que se le resecaron completamente con exéresis de ganglios palpables. El estudio histopatológico informó que se trataba de un carcinoma ductal infiltrante no especificado. Se indicó tratamiento adyuvante con tamoxifeno y radioterapia; en la actualidad está libre de enfermedad. Conclusiones: el carcinoma mamario bilateral sincrónico en el varón es una enfermedad poco frecuente. Su tratamiento principal es la cirugía, de ahí la importancia del diagnóstico temprano. En la mayoría de los casos se requiere quimioterapia y radioterapia adyuvante porque suelen diagnosticarse en un estadio avanzado.

Resultados en el tratamiento quirúrgico de los neurinomas del acústico gigantes / Results in the surgical treatment of giant acoustic neuromas

Introducción y objetivos: Comparar los resultados obtenidos en la resección de 21 schwanomas vestibulares gigantes, mediante vía retrosigmoidea y combinada retrosigmoidea/translaberíntica en cuanto a complicaciones intra y postoperatorias, preservación del nervio facial y secuelas posquirúrgicas. Métodos: Se realiza un estudio retrospectivo de 21 pacientes a los que se practicó resección de neurinoma vestibular gigante según la escala de Tos & Thomsen (igual o mayor a 4cm), en un hospital de tercer nivel en el periodo entre 2000 y 2008. Se presentan las características más significativas de la serie estudiada, y se analizan las ventajas e inconvenientes de los distintos abordajes, comparando los resultados obtenidos. Asimismo, se analizan los resultados en cuanto a la preservación de la función del nervio facial. Resultados: Destaca la ausencia de mortalidad en el grupo de 21 pacientes estudiado. No hubo complicaciones intraoperatorias importantes. Se consiguió la resección total de la lesión en el 87% de los casos, con una preservación anatómica del nervio facial del 73% en el abordaje combinado retrosigmoideo/translaberíntico, respecto a un 40% en el retrosigmoideo. La función del nervio facial a los dos años fue aceptable o buena en un 67% (incluyendo los resultados de las anastomosis heteronerviosas). Se observó un porcentaje global del 14,3% de fístula de líquido cefalorraquídeo y un 9,5% de meningitis. Conclusiones: nuestros resultados demuestran que el abordaje combinado retrosigmoideo translaberíntico para el tratamiento de schwannomas gigantes ofrece mayor preservación del nervio facial y disminución de la morbilidad, siendo una importante opción en el tratamiento de estos tumores, gracias a un enfoque multidisciplinar(AU)

Introduction and objectives: To compare the results obtained in the resection of 21 giant vestibular schwannomas via retrosigmoid (RS) and combined retrosigmoid/translabyrinthine (RS/TL) approaches with respect to intra- and postoperative complications, facial nerve preservation and postsurgical sequelae. Methods: This was a retrospective study of 21 patients who underwent a resection of a giant vestibular neuroma according to the Tos & Thomsen Scale (greater than or equal to 4 centimetres) in a tertiary care centre in the period between 2000 and 2008. We present the most significant characteristics of the series studied and the analysis of the advantages and inconveniences of each approach. We also analyse the results regarding facial nerve function preservation. Results: We highlight the absence of mortality in the 21-patient group. There were no important intraoperative complications. Total resection of the lesion was achieved in the 87% of the cases, with facial nerve preservation of 73% using the combined RS/TL approach, in comparison to 40% using the RS. Facial nerve function after two years was acceptable or good in 67% (including those with heteronerve anastomosis). A global percentage of 14.3% of cerebrospinal liquid fistula was observed, as well as 9.5% of meningitis. Conclusions: The results of the study demonstrate that the combined retrosigmoid translabyrinthine approach for giant schwannoma treatment offers increased facial nerve preservation and lower morbidity, constituting an important option in the treatment of this kind of tumours thanks to a multidisciplinary approach(AU)

[Results in the surgical treatment of giant acoustic neuromas]. / Resultados en el tratamiento quirúrgico de los neurinomas del acústico gigantes.

INTRODUCTION AND OBJECTIVES: To compare the results obtained in the resection of 21 giant vestibular schwannomas via retrosigmoid (RS) and combined retrosigmoid/translabyrinthine (RS/TL) approaches with respect to intra- and postoperative complications, facial nerve preservation and postsurgical sequelae. METHODS: This was a retrospective study of 21 patients who underwent a resection of a giant vestibular neuroma according to the Tos & Thomsen Scale (greater than or equal to 4 centimetres) in a tertiary care centre in the period between 2000 and 2008. We present the most significant characteristics of the series studied and the analysis of the advantages and inconveniences of each approach. We also analyse the results regarding facial nerve function preservation. RESULTS: We highlight the absence of mortality in the 21-patient group. There were no important intraoperative complications. Total resection of the lesion was achieved in the 87% of the cases, with facial nerve preservation of 73% using the combined RS/TL approach, in comparison to 40% using the RS. Facial nerve function after two years was acceptable or good in 67% (including those with heteronerve anastomosis). A global percentage of 14.3% of cerebrospinal liquid fistula was observed, as well as 9.5% of meningitis. CONCLUSIONS: The results of the study demonstrate that the combined retrosigmoid translabyrinthine approach for giant schwannoma treatment offers increased facial nerve preservation and lower morbidity, constituting an important option in the treatment of this kind of tumours thanks to a multidisciplinary approach.

Leucoencefalopatía posterior reversible secundaria a glomerulonefritis postestreptocócica: a propósito de un caso / Posterior leukoencephalopath syndrome in poststretococcal acute glomerulonephritis

La leucoencefalopatía posterior reversible (LEPR) es una entidad clínico radiológica que afecta habitualte la sustancia blanca de los hemisferios cerebrales. Se asocia con frecuencia a hipertensión arterial aguda y al tratamiento inmunosupresor, entre otras causas. La presentación clínica es variada, con cefales, náuseas, vómitos, deterioro de conciencia y alteración en el comportamiento, convulsiones y transtornos visuales, síntomas que frecuentemente retroceden . La tomografía axial computada (TAC) y la resonancia magnética nuclear (RMN) muestran imágenes con edema de la sustancia blanca predominando en regiones posteriores del encéfalo. Se presenta un niño de 10 años con LEPR en el curso de un síndrome nefrítico secundario a una glomerunefritis difusa aguda (GNDA) postestreptocócica.

Intoxicación por carbamazepina / Intoxication by carbamazepine

Se presenta el caso clínico de un paciente de 13 años, portador de una epilepsia secundaria en tratamiento irregular con carbamazepina que consultó en el Departamento de Emergencia por presentar convulsiones y coma. En el momento de la admisión consideraron varias hipótesis diagnósticas. Se constataron cifras muy elevadas de carbamazepina en sangre y el adolescente relató, luego de recuperar la conciencia, que había ingerido el fármaco intencionalmente. Recibió tratamiento con medidas de sostén y tuvo buena evolución clínica.