Intracranial complications of sinogenic and otogenic infections in children: an ESPN survey on their occurrence in the pre-COVID and post-COVID era.

BACKGROUND: COVID-19 pandemic is thought to have changed the epidemiology of some pediatric neurosurgical disease: among them are the intracranial complications of sinusitis and otitis (ICSO). According to some studies on a limited number of cases, both streptococci-related sinusitis and ICSO would have increased immediately after the pandemic, although the reason is not clear yet (seasonal changes versus pandemic-related effects). The goal of the present survey of the European Society for Pediatric Neurosurgery (ESPN) was to collect a large number of cases from different European countries encompassing the pre-COVID (2017-2019), COVID (2020-2021), and post-COVID period (2022-June 2023) looking for possible epidemiological and/or clinical changes. MATERIAL AND METHODS: An English language questionnaire was sent to ESPN members about year of the event, patient's age and gender, presence of immune-deficit or other favoring risk factors, COVID infection, signs and symptoms at onset, site of primary infection, type of intracranial complication, identified germ, type and number of surgical operations, type and duration of medical treatment, clinical and radiological outcome, duration of the follow-up. RESULTS: Two hundred fifty-four cases were collected by 30 centers coming from 14 different European countries. There was a statistically significant difference between the post-COVID period (129 children, 86 cases/year, 50.7% of the whole series) and the COVID (40 children, 20 cases/year, 15.7%) or the pre-COVID period (85 children, 28.3 cases/year, 33.5%). Other significant differences concerned the presence of predisposing factors/concurrent diseases (higher in the pre-COVID period) and previous COVID infection (higher in the post-COVID period). No relevant differences occurred as far as demographic, microbiological, clinical, radiological, outcome, morbidity, and mortality data were concerned. Paranasal sinuses and middle ear/mastoid were the most involved primary site of infection (71% and 27%, respectively), while extradural or subdural empyema and brain abscess were the most common ICSO (73% and 17%, respectively). Surgery was required in 95% of cases (neurosurgical and ENT procedure in 71% and 62% of cases, respectively) while antibiotics in 99% of cases. After a 12.4-month follow-up, a full clinical and radiological recovery was obtained in 85% and 84% of cases, respectively. The mortality rate was 2.7%. CONCLUSIONS: These results suggest that the occurrence of ICSO was significantly increased after the pandemic. Such an increase seems to be related to the indirect effects of the pandemic (e.g., immunity debt) rather than to a direct effect of COVID infection or to seasonal fluctuations. ICSO remain challenging diseases but the pandemic did not affect the management strategies nor their prognosis. The epidemiological change of sinusitis/otitis and ICSO should alert about the appropriate follow-up of children with sinusitis/otitis.

Empiric treatment vs susceptibility-guided treatment for eradicating H. pylori: Is it possible to change that paradigm using modern molecular methods?

Helicobacter pylori (H. pylori) infection is the most widespread infectious-contagious disease worldwide, reaching a prevalence of 50-80% in developing countries. Chronic infection is considered the main cause of chronic gastritis and has been related to other diseases, such as peptic ulcer, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. The most common treatment is with eradication regimens that utilize three or four drugs, including a proton pump inhibitor (PPI) and the antibiotics, clarithromycin and amoxycillin or metronidazole. Empiric antibiotic use for eradicating the bacterium has led to a growing resistance to those drugs, reducing regimen efficacy and increasing costs for both the patient and the healthcare sector. In such a context, the development of noninvasive next-generation molecular methods holds the promise of revolutionizing the treatment of H. pylori. The genotypic and phenotypic detection of the resistance of the bacterium to antibiotics enables personalized treatment regimens to be provided, reducing costs and implementing an antibiotic stewardship program. The aims of the present narrative review were to analyze and compare the traditional and next-generation methods for diagnosing H. pylori, explain the different factors associated with eradication failure, and emphasize the impact of the increasing antibiotic resistance on the reversal and prevention of H. pylori-associated diseases.

Megalencephaly-capillary malformation syndrome and associated hydrocephalus: treatment options and revision of the literature.

PURPOSE: We describe our series of 4 patients with megalencephaly-capillary malformation syndrome (MCAP) and review the literature in order to assess the optimal treatment for the associated hydrocephalus. METHODS: We review our institutional series of hydrocephalus associated with MCAP and review the literature, analyzing the causes that could originate the hydrocephalus and the different types of treatments proposed for them. RESULTS: Of our patients treated with ventriculoperitoneal (VP) shunt, one suffered a surgical revision of the shunt and died due to a cranial trauma unrelated to her syndrome or the previous shunt surgery, and the other did not undergo surgical revisions until the end of her follow-up. Our patients treated with endoscopic third ventriculostomy (ETV) have improved their symptomatology and have not suffered of any complications related to the hydrocephalus after the ETV surgery. CONCLUSIONS: We update the treatment of MCAP-associated hydrocephalus and propose ETV as a valid treatment, as it seems a safe procedure with a low rate of complications.

Nitrous oxide versus lidocaine versus no analgesic for in-office hysteroscopy: a randomised clinical trial.

OBJECTIVE: To compare the effect of inhaled nitrous oxide (INO) on pain control during in-office hysteroscopy with 1% lidocaine paracervical infiltration and no analgesic. DESIGN: Single-blind stratified randomised clinical trial with masked assessment by a third party. SETTING: Department of Obstetrics and Gynaecology in a Spanish hospital. POPULATION: Women who underwent hysteroscopy. METHODS: Patients were stratified into three groups according to the purpose of the hysteroscopy (biopsy, polypectomy or tubal sterilisation) and then assigned to different treatment groups through a permuted-blocks randomisation within strata. Pain scale was provided by a gynaecologist totally blinded to procedures and treatments. Effects were assessed using a one-way analysis of variance following an intention-to-treat approach. MAIN OUTCOME MEASURES: Visual analogue scale (VAS) from 0 to 100 mm. RESULTS: A total of 314 women were included: 105 to INO, 104 to 1% lidocaine and 105 to no analgesic. Baseline characteristics were comparable. Mean VAS score after the procedure was 34.7 ± 25.8 mm, 36.1 ± 22.9 mm (P = 1.0) and 47.3 ± 28.2 mm (P = 0.001) for INO, 1% lidocaine and no analgesic, respectively. No adverse events were reported in 91 (86.7%) patients in the INO group compared with 79 (76%) in the 1%-lidocaine group (P = 0.04) and 85 (81%) in the no-analgesic group (P = 0.26). CONCLUSION: INO was as effective as 1% lidocaine in pain control for in-office hysteroscopy and was better tolerated. The no-analgesic group presented the poorer results, so was the least recommended clinical option.

Gliomatosis cerebri and Rasmussen's encephalitis: Two different entities causing refractory epilepsy. Comparison through two clinical cases.

BACKGROUND AND IMPORTANCE: Rasmussen's Encephalitis (RE) is a chronic and progressive childhood disease caused by an inflammatory disorder that affects a cerebral hemisphere. On the other hand, Gliomatosis Cerebri (GC) is a rare primary neoplastic glial process with a diffuse and infiltrative growth. CLINICAL PRESENTATION: We present two clinical cases with a history of continuous focal epilepsy refractory to antiepileptic drugs. They share similar clinical and radiologic features, but a different histopathological diagnosis. A brain biopsy was needed to distinguish GC from a RE. CONCLUSION: The debut of a drug-resistant epilepsy with focal seizures and an ipsilateral progressive hemiparesis suggests the diagnosis of RE. However, there are other entities such as GC, which, despite its rarity, should be considered in the differential diagnosis. So, in some cases, histological diagnosis is needed.

Phenotype and natural history of elderly onset inflammatory bowel disease: a multicentre, case-control study.

BACKGROUND: Onset during old age has been reported in upto 10% of total cases of inflammatory bowel disease (IBD). AIM: To evaluate phenotypic characteristics and the use of therapeutic resources in patients with elderly onset IBD. METHODS: Case-control study including all those patients diagnosed with IBD over the age of 60 years since 2000 who were followed-up for >12 months, identified from the IBD databases. Elderly onset cases were compared with IBD patients aged 18 to 40 years at diagnosis, matched by year of diagnosis, gender and type of IBD (adult-onset). RESULTS: One thousand three hundred and seventy-four elderly onset and 1374 adult-onset cases were included (62% ulcerative colitis (UC), 38% Crohn's disease (CD)). Among UC patients, elderly onset cases had a lower proportion of extensive disease (33% vs 39%; P < 0.0001). In CD, elderly onset cases showed an increased rate of stenosing pattern (24% vs 13%; P < 0.0001) and exclusive colonic location (28% vs 16%; P < 0.0001), whereas penetrating pattern (12% vs 19%; P < 0.0001) was significantly less frequent. Regarding the use of therapeutic resources, there was a significantly lower use of corticosteroids (P < 0.0001), immunosuppressants (P < 0.0001) and anti-TNFs agents (P < 0.0001) in elderly onset cases. Regarding surgery, we found a significantly higher surgery rate among elderly onset UC cases (8.3% vs 5.1%; P < 0.009). Finally, elderly onset cases were characterised by a higher rate of hospitalisations (66% vs 49%; P < 0.0001) and neoplasms (14% vs 0.5%; P < 0.0001). CONCLUSIONS: Elderly onset IBD shows specific characteristics and they are managed differently, with a lower use of immunosuppressants and a higher rate of surgery in UC.

Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study.

OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed. METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included. RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe. CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

Clinical considerations and surgical approaches for low-grade gliomas in deep hemispheric locations: insular lesions.

Insula and paralimbic region represent a common location for gliomas in adulthood. However, limbic and paralimbic tumors are rare in children. Reports of pediatric insular tumors are scarce in literature, and most of them are included in adult's series, so their management and outcome can be outlined only after extracting data from these reports. Due to their predominantly low grade, they usually have a benign course for some time, what make them ideal candidates for total resection. However, their intricate location and spread to key areas, including the temporal lobe, make them a surgical challenge. The transsylvian route, with or without resection of the frontal and/or temporal operculae, which requires exposure of part or all of the insula is commonly selected for insular tumor approaches. Intraoperative functional mapping is a standard procedure for resection of central region tumors in adults. In children and young individuals, awake craniotomy is not always possible and surgical planning usually relay on functional and anatomical preoperative studies. The main goal when approaching an insular tumor is to achieve the largest extent of resection to increase overall patient survival while preserving the functional status, minimizing postoperative morbidity and increasing the quality of life. The extent of resection seems to be correlated also with the control of associated (and usually intractable) epilepsy.

Standardization of the homogeneous mobility shift assay protocol for evaluation of anti-infliximab antibodies. Application of the method to Crohn's disease patients treated with infliximab.

BACKGROUND: The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would facilitate the implementation of therapeutic drug monitoring in clinical decision-making. Our aim was to standardize the homogeneous mobility shift assay (HMSA) used in the measure of ATI levels. METHODS: In this prospective longitudinal multicenter study, 50 IFX-treated Crohn's disease (CD) patients were followed up for 54weeks. During this period 360 human serum samples were analysed. Monomeric ATI levels were measured by a quantitative HMSA-method using an anti-IFX calibrator. IFX trough levels measured by ELISA were correlated with ATI levels. RESULTS: Using HMSA and a pure anti-idiotypic monoclonal antibody specific for IFX (anti-IFX calibrator), we measured the levels of monomeric ATI generated in Crohn's disease patients treated with IFX. Anti-IFX calibrator allowed to quantify monomeric antibodies against IFX with a low limit of quantification (3nM). The threshold level of ATI in order to classify the immunogenicity of the patients was 10nM. We observed that 24% (12/50) of IFX-treated patients developed ATI (>10nM) during the observation period (54weeks). Serum concentration of ATI higher than 10nM dramatically increased the probability (OR=51.1; 95% CI: 20.4-128.0; p<0.0001) of presenting low levels of IFX (⩽1.5nM) in serum, as observed in some CD patients treated with standard doses of the drug. CONCLUSIONS: The HMSA-method described here allows an accurate quantification of ATI concentration in international units (IU) and therefore it could be useful in the study of the relationship between ATI concentration, infliximab level and the clinical response to the drug.

M1 Macrophages Activate Notch Signalling in Epithelial Cells: Relevance in Crohn's Disease.

BACKGROUND: The Notch signalling pathway plays an essential role in mucosal regeneration, which constitutes a key goal of Crohn's disease (CD) treatment. Macrophages coordinate tissue repair and several phenotypes have been reported which differ in the expression of surface proteins, cytokines and hypoxia-inducible factors (HIFs). We analysed the role of HIFs in the expression of Notch ligands in macrophages and the relevance of this pathway in mucosal regeneration. METHODS: Human monocytes and U937-derived macrophages were polarized towards the M1 and M2 phenotypes and the expression levels of HIF-1α, HIF-2α, Jagged 1 (Jag1) and delta-like 4 (Dll4) were evaluated. The effects of macrophages on the expression of hairy and enhancer of split-1 (HES1, the main target of Notch signalling) and intestinal alkaline phosphatase (IAP, enterocyte marker) in epithelial cells in co-culture were also analysed. Phenotype macrophage markers and Notch signalling were evaluated in the mucosa of CD patients. RESULTS: M1 macrophages were associated with HIF-1-dependent induction of Jag1 and Dll4, which increased HES1 protein levels and IAP activity in co-cultured epithelial cells. In the mucosa of CD patients a high percentage of M1 macrophages expressed both HIF-1α and Jag1 while M2 macrophages mainly expressed HIF-2α and we detected a good correlation between the ratio of M1/M2 macrophages and both HES1 and IAP protein levels. CONCLUSION: M1, but not M2, macrophages are associated with HIF-1-dependent induction of Notch ligands and activation of epithelial Notch signalling pathway. In the mucosa of chronic CD patients, the prevalence of M2 macrophages is associated with diminution of Notch signalling and impaired enterocyte differentiation.

Hypoxic macrophages impair autophagy in epithelial cells through Wnt1: relevance in IBD.

A defective induction of epithelial autophagy may have a role in the pathogenesis of inflammatory bowel diseases. This process is regulated mainly by extracellular factors such as nutrients and growth factors and is highly induced by diverse situations of stress. We hypothesized that epithelial autophagy is regulated by the immune response that in turn is modulated by local hypoxia and inflammatory signals present in the inflamed mucosa. Our results reveal that HIF-1α and Wnt1 were co-localized with CD68 in cells of the mucosa of IBD patients. We have observed increased protein levels of ß-catenin, phosphorylated mTOR, and p62 and decreased expression of LC3II in colonic epithelial crypts from damaged mucosa in which ß-catenin positively correlated with phosphorylated mTOR and negatively correlated with autophagic protein markers. In cultured macrophages, HIF-1 mediated the increase in Wnt1 expression induced by hypoxia, which enhanced protein levels of ß-catenin, activated mTOR, and decreased autophagy in epithelial cells in co-culture. Our results demonstrate a HIF-1-dependent induction of Wnt1 in hypoxic macrophages that undermines autophagy in epithelial cells and suggest a role for Wnt signaling and mTOR pathways in the impaired epithelial autophagy observed in the mucosa of IBD patients.

[Iris mammillations. Three case reports]. / Mamelones de iris. A propósito de tres casos.

CLINICAL CASES: We report the cases of 3 young patients who were seen in our hospital with the diagnosis of iris mammillations. Two of them were bilateral without familial association. The third child had iris mammillations as part of an ocular melanocytosis. None of them had abnormalities in the posterior segment or the pachymetry. DISCUSSION: The discovery of iris mammillations during an examination requires a long term follow up of these patients due to its association with uveal melanoma. This is required whether it is a casual discovery or in the presence of ocular melanocytosis.

Brachytherapy versus radical hysterectomy after external beam chemoradiation with gemcitabine plus cisplatin: a randomized, phase III study in IB2-IIB cervical cancer patients.

BACKGROUND: The aim of the present study was to demonstrate that radical hysterectomy (RH) leads to improved survival outcomes in FIGO stage IB2-IIB cervical cancer when compared with standard brachytherapy (BCT) after identical external beam chemoradiation (EBRT-CT). PATIENTS AND METHODS: EBRT-CT treatment consisted of six courses of cisplatin at 40 mg/m² and gemcitabine at 125 mg/m² per week concurrent with 50.4 Gy of radiation. In the BCT arm, EBRT-CT was followed by BCT to reach a point A dose of 85 Gy, whereas in the experimental arm, a type III RH with bilateral pelvic lymph node dissection and para-aortic lymph node sampling (RH) was carried out within 4-6 weeks after EBRT-CT. RESULTS: Between May 2004 and June 2009, 211 patients were enrolled (BCT, 100 and RH, 111). At a median follow-up time of 36 months (3-80), progression-free survival (PFS) and overall survival (OS) rates were similar in both the arms. PFS rates were 74.8% and 71.7% in the BCT and RH arms [HR 0.6516 (95% confidence interval (CI) 0.3504-1.2116)], P = 0.186. OS rates were 76.3% in the BCT versus 74.5% in the surgical arm [HR 0.6981 (95% CI 0.3106-1.3439)], P = 0.236. No differences were observed in the pattern of local and systemic failures. CONCLUSIONS: This study failed to demonstrate that RH after EBRT-CT is superior to standard BCT.

[Magnetic resonance enterography: technique and indications. Findings in Crohn's disease]. / Enterografía por resonancia magnética: técnica e indicaciones. Hallazgos en la enfermedad de Crohn.

Radiology with oral contrast, or enteroclysis, have traditionally been the techniques of choice in the examination of the small intestine, due to the excellent visualisation of the mucosal pattern. However, the absence of extra-luminal information and the use of ionising radiation have replaced these examinations with sectional techniques which enable the abdominal cavity to be viewed with good resolution. Magnetic resonance enterography is a simple technique, with no ionising radiation, provided quality images, distends the intestinal lumen well by the administration of non-reabsorbable oral substances, minimises peristalsis, and establishes a protocol which includes sequences with intravenous contrast. These properties can be used in patients with Crohn's disease, achieving good diagnostic precision in the assessment of activity and monitoring of treatment, in intestinal obstruction, in the suspicion of small intestine tumours, and in paediatric patients due to it being harmless.

Endoscopic-assisted treatment of trigonocephaly.

Minimally invasive, endoscopic repair of metopic craniosynostosis has emerged as a potentially efficacious, safe, and aesthetically acceptable alternative to open procedures. Potential advantages of an early endoscopic approach to repair metopic craniosynostosis include a reduction in blood loss and consequent decreases in transfusion volumes, decreased hospital costs, shorter operative times, and limited duration of hospitalization. Other benefits of minimally invasive techniques would be avoidance of anaesthetic surgical scarring, decrease in postoperative swelling and discomfort, and lower rate of complications such as duramater tears, postoperative hyperthermia, or infection. However, a concern is usually raised about the achievements of the "endoscopic" techniques when compared to "standard" open approaches. The indications for endoscopic-assisted surgery in the treatment of trigonocephaly remain controversial and further series and follow-up of these patients are necessary to set up the role of these approaches.

Adherence of gastroenterologists to European Crohn's and Colitis Organisation consensus on Crohn's disease: a real-life survey in Spain.

BACKGROUND: There is no information as to the extent by which Spanish gastroenterologists adhere to Crohn's disease (CD) management guidelines. The objective of this study was to evaluate the degree of adherence of Spanish gastroenterologists to the European Crohn's and Colitis Organisation (ECCO) guidelines and to determine whether differences in adherence exist between gastroenterologists specialized in inflammatory bowel diseases (GSIBDs) and general gastroenterologists (GGs). METHODS: This was a prospective, nation-wide, questionnaire-based survey covering aspects related to diagnosis, treatment, follow-up, and safety considered by the physicians in their daily management of CD, as well as demographic traits seen in clinical practice. RESULTS: The overall degree of adherence to guidelines by both GSIBDs and GGs was high. However, the use of imaging techniques in diagnosis, follow-up, and in relapsed patients differed between the two groups. In the diagnosis of perianal disease, GSIBDs used magnetic resonance and surgical exploration under anesthesia more frequently than GGs. In terms of therapeutic choices, the adherence to guidelines was good in both groups. However, GSIBDs showed significantly higher adherence in some areas: thiopurines were used less in refractory cases and methotrexate was used more commonly in corticoid-dependent, azathioprine-intolerant patients, and in patients under biological treatment. Request for infection studies and vaccinations at diagnosis or prior to treatment was more common among GSIBDs. CONCLUSIONS: Guideline adherence among Spanish gastroenterologists is high. However, there are significant differences between IBD-specialized (more adherent in general) and non-specialized gastroenterologists.

Long-term durability of response to adalimumab in Crohn's disease.

BACKGROUND: Adalimumab is an effective treatment for Crohn's disease (CD), but may also be associated with loss of response. Few reports provide insight into the durability of treatment of CD with adalimumab for periods longer than 12 months in clinical practice. AIMS: To evaluate the long-term durability of adalimumab maintenance treatment and to identify predictive factors associated with loss of response. METHODS: CD patients who initially responded to adalimumab were evaluated in a historical cohort study. Maintenance of long-term response was estimated using Kaplan-Meier analysis. Cox regression analysis was performed to identify potential predictive factors for loss of efficacy. RESULTS: In all, 380 CD patients were included (mean age, 38 years; 52% female). Of these, 43% had ileocolic CD, 50% inflammatory CD, and 41% perianal CD. Median follow-up with adalimumab was 8 months (range, 4-75 months). The annual risk of loss of response to adalimumab was 18% per patient-year of follow-up. Twenty-eight percent of patients were anti-TNF-naïve and 72% anti-TNF-experienced. The loss of efficacy was 8% per patient-year of follow-up in the anti-TNF-naïve patients and 22% in the anti-TNF-experienced group (P < 0.01). In the multivariate analysis, the presence of extraintestinal manifestations (hazard ratio [HR] = 1.7; 95% confidence interval [CI] = 1.02-2.9) and previous experience with other anti-TNF agents (HR = 2.5,95% CI = 1.2-5.3) were associated with higher risk of loss of efficacy. CONCLUSIONS: A relevant proportion of CD patients on long-term adalimumab lost response. The risk of loss of response was higher (more than 2-fold) in anti-TNF-experienced than in anti-TNF-naïve patients (22% vs. 8% per patient-year of treatment). Having extraintestinal manifestations seems to increase the risk of loss of efficacy.