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.

Primary mediastinal large B-cell lymphoma: Outcome of a series of pediatric patients treated with high-dose methotrexate and cytarabine plus anti-CD20.

Between 2007 and 2013, 13 children diagnosed with primary mediastinal large B-cell lymphoma (PMLBL) were treated according to a modified version of AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) LNH-97 protocol based on high-dose methotrexate, anthracyclines, and addition of anti-CD20. Ten patients achieved a continuous complete remission with front-line therapy. The overall 5-year survival was 91.7%, and event-free survival was 83.9%, with only one patient dying of progressive disease. Despite the few cases, these results demonstrate that this therapy, which includes anti-CD20, given in a multicenter setting, is feasible with acceptable toxicity in children with PMLBL.

Metastatic neuroblastoma in infants: are survival rates excellent only within the stringent framework of clinical trials?

INTRODUCTION: SIOPEN INES protocol yielded excellent 5-year survival rates for MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to lack or delay of MYCN status or late registration were treated, but not included in the study. Our goal was to analyse survival at 10 years among the whole population. MATERIALS AND METHODS: Italian and Spanish metastatic INES patients' data are reported. SPSS 20.0 was used for statistical analysis. RESULTS: Among 98 infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and 74 %, respectively. MYCN status was significant for EFS, but not for OS in multivariate analysis. CONCLUSIONS: The survival rates of patients who complied with all the inclusion criteria for INES trials are higher compared to those that included also not registered patients. Five-year EFS and OS for INES 99.2 were 87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning 99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61 and 68 %. MYCN amplification had a strong impact on prognosis and therefore we consider it unacceptable that many patients were not studied for MYCN and probably inadequately treated. Ten-year survival rates were shown to decrease: EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events, particularly in stage 4s. Population-based registries like European ENCCA WP 11-task 11 will possibly clarify these data.

El acceso vascular sigue siendo un problema a resolver / Vascular access is still an unresolved problem

El acceso vascular para el tratamiento endovascular de los aneurismas de aorta puede ser una limitante o una causa grave de morbilidad o mortalidad. La presunción, la posibilidad de realizarmaniobras adyuvantes o la combinación con cirugía abierta pueden ser determinantes al momento de planear o finalizar el procedimiento. Se describen una variedad de procedimientos utilizados para modificar la anatomía desfavorable de las arterias ilíacas. La angioplastía con dilatadores o balón, la utilización de ciertas guías y accesos o la realización de conductos pueden ser claves al momento de realizar la cirugía.

O acesso vascular para o tratamento endovascular dos aneurismas da aorta pode ser uma limitante ou uma causa grave de morbilidade ou mortalidade. Como presunção, a possibilidade derealizar manobras adjuvantes ou a combinação com cirurgia aberta podem ser determinantes no momento de planejar ou finalizar o procedimento. Descrevem-se uma variedade de procedimentos utilizados para modificar a anatomia desfavorável das artérias ilíacas. A angioplastia com dilatadores ou balão, a utilização de certas guias e acessos ou a realização de canais podem ser fundamentais no momento de realizar a cirurgia.

The vascular access in the treatment of aortic aneurysms may be a limiting factor or a severe cause of morbidity and mortality. The possibility of carrying out adjuvant procedures or combiningthem with open surgery may be determining factors at the moment of planning or completing the procedure. A series of procedures used to modify the unfavourable anatomy of the iliac arteries are here in described. Dilator or balloon angioplasty, the use of certain guidewires and routes of access or the carrying out of conduits may be key at the moment of carrying out the surgery.

Muscle metastasis from hepatocellular carcinoma in a patient treated with TACE.

The authors describe a rare case of hepatocellular carcinoma that metastasized to the pectineal muscle of the right thigh. The patient had been treated with surgical procedures and with multiple sessions of transarterial chemoembolization, one of which was complicated by a right femoral artery hematoma at the catheter insertion site. It is unclear whether the muscle metastasis was caused by blood-borne spread or by tumor-cell seeding caused by the TACE procedure.

A highly accurate method for monitoring histological recovery in patients with celiac disease on a gluten-free diet using an endoscopic approach that avoids the need for biopsy: a double-center study.

BACKGROUND AND STUDY AIM: Endoscopy with duodenal biopsy is often performed in order to assess histological recovery in patients with celiac disease who are on a gluten-free diet. Use of the "immersion" technique during upper endoscopy allows visualization of duodenal villi or detection of total villous atrophy. In this two-center study, we investigated the accuracy of the immersion technique in predicting histological recovery in patients on a gluten-free diet whose initial diagnosis of celiac disease had been made on the basis of total villous atrophy. PATIENTS AND METHODS: The immersion technique was performed in 62 patients with celiac disease who were being treated and who had been referred for follow-up (26 patients at the Rome center and 36 patients at the Vicenza center). All these patients had an initial diagnosis based on positive antibodies and biopsy-proved duodenal total villous atrophy. At the follow-up examination, the duodenal villi were re-evaluated as present or absent by one endoscopist at each center, and the results were compared with the histology. RESULTS: At the follow-up endoscopy, the duodenal villi were found to be present in 51 patients and absent in 11. The sensitivity, specificity, positive predictive value, and negative predictive value of the immersion technique for detecting the presence or absence of villi were all 100 %. CONCLUSIONS: This study demonstrated the feasibility and the high level of accuracy of the immersion technique in predicting the histological recovery of duodenal villi in patients with celiac disease who are following a gluten-free diet. An endoscopy-based approach that avoids the need for biopsy could be useful for monitoring the dietary adherence and/or response of patients with an initial diagnosis of celiac disease based on total villous atrophy.

Intra-aneurysmal pressure after incomplete endovascular exclusion.

PURPOSE: An endoleak results from the incomplete endovascular exclusion of an aneurysm. We developed an experimental model to analyze hemodynamic changes within the aneurysm sac in the presence of an endoleak, with and without a simulated open collateral branch. METHODS: With a latex aneurysm model connected to a pulsatile pump, pressures were measured simultaneously within the system (systemic pressure) and the aneurysm sac (intrasac pressure). The experiments were performed without endoleak (control group) and after creating a 3.5-mm (group 1), 4.5-mm (group 2), and 6-mm (group 3) diameter orifice in the endograft, simulating an endoleak. Pressures were also registered with and without a patent aneurysm side branch. RESULTS: In each endoleak group, the intrasac diastolic pressure (DP) and mean pressure (MP) were significantly higher than the systemic DP and MP (P =.01, P =.006, and P =.001, respectively), although the pressure curve was damped. The presence of an open side branch significantly reduced the intrasac DP and MP. CONCLUSION: In this model, intrasac pressures were significantly higher than systemic pressures in the presence of all endoleaks, even the smallest ones. Intrasac pressures higher than systemic pressure may pose a high risk for aneurysm rupture. Although patent side branches significantly reduce these pressures, the aggressive management of an endoleak should be pursued.

Increased activity of membrane-associated nucleoside diphosphate kinase and inhibition of cAMP synthesis in failing human myocardium.

OBJECTIVE: Chronic heart failure is associated with a decreased responsiveness of the heart to beta-adrenergic receptor agonists. We recently demonstrated a receptor-independent activation of G proteins and modulation of cardiac adenylyl cyclase activity by sarcolemmal membrane-associated nucleoside diphosphate kinase. We wondered whether changes in the activity of nucleoside diphosphate kinase occur in heart failure and contribute to or compensate for the impairment in myocardial receptor-mediated cAMP generation. METHODS: Sarcolemmal membranes were purified from non-failing and failing human left ventricular myocardium. The protein level and activity of nucleoside diphosphate kinase were quantified. The influence of nucleoside diphosphate kinase on adenylyl cyclase activity was determined by measuring the effect of GDP on adenylyl cyclase activity in the absence and presence of nucleoside diphosphate kinase inhibitors. RESULTS: The amount and activity of nucleoside diphosphate kinase in sarcolemmal membranes from failing hearts (n=13) were increased 3- to 4-fold compared to levels in membranes from non-failing myocardium (n=5). This increase in sarcolemmal nucleoside diphosphate kinase activity resulted in a 50% inhibition of adenylyl cyclase activity over a range of GDP and ATP concentrations. CONCLUSION: The amount and activity of nucleoside diphosphate kinase are increased in sarcolemmal membranes of failing human myocardium, resulting in a substantial receptor-independent inhibition of adenylyl cyclase activity.

Initial evaluation of carotid angioplasty and stenting with three different cerebral protection devices.

OBJECTIVE: The purpose of the study was to assess the effectiveness of cerebral protection devices during carotid artery angioplasty and stent placement. METHODS: Between September 1998 and September 1999, carotid angioplasty and stenting were performed in 46 patients with symptomatic (39.1%) or asymptomatic (60.9%) severe carotid artery stenosis. Wallstents were used in all patients with selective predilatation. Cerebral protection devices were used in 25 of these patients. Primary end points were perioperative neurologic complications and mortality. Data were collected prospectively. RESULTS: The overall combined end point of all neurologic deficits and death rate was 4.34%. Two neurologic events (one transient ischemic attack and one minor stroke) occurred in the unprotected group (9.53%) versus none in the group with cerebral protection. This difference is not statistically significant. The mortality rate was 0% for both groups. On an intention to treat basis, the overall technical success rate for carotid angioplasty was 97.8%, and for placement of cerebral protection devices it was 100%. An important number of particles of different sizes were captured in all cases in which cerebral protection devices were used. CONCLUSION: Experience has shown that cerebral protection during carotid angioplasty and stenting is technically feasible and appears to be effective in preventing procedure-related neurologic complications. Further investigation is warranted.

Bloodstream infections in children with cancer: a multicentre surveillance study of the Italian Association of Paediatric Haematology and Oncology. Supportive Therapy Group-Infectious Diseases Section.

A one-year prospective, multicentre surveillance study on aetiology, main clinical features and outcome of bloodstream infections in children with cancer was conducted in 18 paediatric haematology centres belonging to the Italian Association for Paediatric Haematology and Oncology. A total of 191 bloodstream infections were reported during the study period. Of them, 123 (64%) occurred in neutropenic and 68 (36%) in non-neutropenic patients. Gram-positive cocci caused 45% (85/191) of the episodes, gram-negative rods 41% (78/191), and fungi 9% (18/191). The remaining 5% (10/191) of the episodes were poly-microbial infections. A total of 204 pathogens were isolated (46% gram-positive cocci; 44% gram-negative rods; and 10% fungi). The aetiologic distribution was similar among neutropenic and non-neutropenic patients. A correlation between the infection and the presence of an indwelling central venous catheter was found in 20% (23/114) of the episodes among neutropenic patients and in 55% (23/62) among non-neutropenic patients. Gram-negative micro-organisms were isolated in an unusually high proportion of catheter-related infections (48%). The overall mortality rate from any cause within 30 days from the first positive blood culture was 11%, and was higher among patients who were neutropenic at the onset of the infection than among those who were not neutropenic (15 versus 4%, P = 0.03). In addition, the mortality was significantly higher in recipients of bone marrow transplantation than in patients with acute leukaemia or solid tumour (21, 11 and 6%, respectively) and was also higher in fungaemias and poly-microbial infections (22 and 30%) than in single gram-positive and gram-negative bacteraemias (11 and 6%).

Evidence against a regulation of Na+/K(+)-ATPase by Gi proteins. Failure to detect an influence of G proteins on Na+/Ca(2+)-exchange in cardiac sarcolemmal membranes.

In the myocardium the inhibitory guanine nucleotide-binding regulatory proteins (Gi proteins) mediate negative chronotropic and negative inotropic effects by activation of K+ channels and inhibition of adenylyl cyclase. The concept of a uniform inhibitory action of Gi proteins on myocardial cellular activity has been questioned by the recent observations of adenosine-induced activation of the Na+/Ca(2+) exchange and a carbachol-induced inhibition of the Na+/K(+)-ATPase activity in cardiac sarcolemmal membranes. The aim of the present study, therefore, was to reinvestigate the putative regulation of Na+/Ca(2+) exchange and Na+/K(+)-ATPase activity in purified canine sarcolemmal membranes. These membranes were enriched in adenosine A1 (Maximum number of receptors, Bmax 0.033 pmol/mg) and muscarinic M2 (Bmax 2.9 pmol/mg) receptors and contained Gi2 and Gi3, two Gi protein isoforms, and G0, another pertussis toxin-sensitive G protein, as detected with specific antibodies. The adenosine A1-selective agonist, (-)-N6-(2-phenylisopropyl)-adenosine, and the muscarinic agonist, carbachol, both inhibited isoprenaline-stimulated adenylyl cyclase activity by 25% and 35% respectively, and the stable GTP analogue 5'-guanylylimidodiphosphate inhibited forskolin-stimulated adenylyl cyclase activity by 35% in these membranes. The characteristics of Na+/Ca(2+) exchange and Na+/K(+)-ATPase activity as well as those of the ouabain-sensitive, K(+)-activated 4-nitrophenylphosphatase, an ATP-independent, partial reaction of the Na+/K(+)-ATPase, were in agreement with published data with regard to specific activity, time course of activity and substrate dependency. However, none of these activities were influenced by adenosine, (-)-N6-(2-phenylisopropyl)-adenosine, carbachol, or stable GTP analogs, suggesting that Na+/Ca(2+) exchange and Na+/K(+)-ATPase are not regulated by Gi proteins in canine cardiac sarcolemmal membranes.

Prognostic value of nephromegaly at diagnosis of childhood acute lymphoblastic leukemia.

In order to assess the prognostic value of nephromegaly (kidney enlargement > or = 2 SD from mean for age) in children at diagnosis of acute lymphoblastic leukemia (ALL), kidney size was investigated by intravenous pyelogram (IP), according to the method of Ekl of and Ringertz, in 101 children diagnosed with ALL in the period of 1975-1983. In the same period 103 additional patients with ALL were not investigated with IP for logistical reasons. Characteristics at the diagnosis of ALL in the patients of the investigated and non-investigated (with IP) groups were quite similar and event-free-survival (EFS) curves superimposable. Eighty-nine (50 males and 39 females, median age 61 months) out of 101 patients underwent IP before starting any therapy and were evaluated in the study; 27 (30.3%) presented with nephromegaly (bilateral in 13 cases and unilateral in 14). With a median follow-up time of 14.4 years (range 11-19 years), the EFS at 15 years from diagnosis was 18.5% (SE 9.5) in the nephromegalic group and 48.4% (SE 6.4) in the non-nephromegalic group. The association of poorer EFS with nephromegaly was confirmed when the comparison was adjusted by white blood cell count and age at diagnosis in a Cox regression model. Nephromegaly at diagnosis of childhood ALL may have an independent prognostic value in patients treated with 'not intensive' protocols; however, this finding should be confirmed in patients treated uniformly with contemporary intensive protocols.

High-dose methotrexate administration and acute liver damage in children treated for acute lymphoblastic leukemia. A prospective study.

BACKGROUND: Methotrexate-induced hepatotoxicity following chronic low-dose administration has been extensively reported. Current protocols now include high-dose methotrexate (HDMTX), but there are few studies providing data on its acute hepatotoxicity in childhood leukemia. METHODS: To evaluate the prevalence of HDMTX-induced acute hepatotoxicity, sixty-eight consecutive children with ALL were prospectively studied from diagnosis to the end of HDMTX courses with biochemical and clinical evaluation performed at regular intervals. RESULTS: Prevalence of HDMTX-induced acute hepatotoxicity was 1.47% (1/68 patients). ALT values did not change in 22% (15/68) and decreased in 76.4% (52/68) after HDMTX infusion. Mean ALT levels calculated in all the patients decreased significantly during HDMTX administration when compared to the values reached during induction (p less than 0.0001). Direct hyperbilirubinemia was present only in the child with HDMTX-related hepatotoxicity. CONCLUSIONS: The use of HDMTX in the treatment of childhood ALL is not associated with major evidence of direct acute hepatotoxic effects, while it may modify the pattern of preexisting liver diseases.

[Incidence, mortality and survival in childhood tumors in meridional Sardinia. The Cagliari province, 1981-1988]. / Incidenza, mortalità e sopravvivenza per tumori infantili nella Sardegna meridionale. La provincia di Cagliari per gli anni 1982-1988.

Childhood cancer incidence, mortality and relative survival rates have been estimated in the province of Cagliari for the years 1982-86. Cases were collected from pediatric and non pediatric units operating either in the province or elsewhere. Deaths were identified through the registry offices of municipal administrations. A total of 151 cases were identified, corresponding to an incidence rate of 115.0 per million. Survival rate at three years of diagnosis was 63.3%.

Evaluation of peritoneovenous shunt patency with Tc-99m labeled microspheres.

The LeVeen peritoneovenous shunt (PVS) was investigated in 40 cirrhotic patients with refractory ascites. Five millicuries of Tc-99m-tagged human albumin microspheres (15-36 microns) were injected into the peritoneal cavity between the umbilicus and the left anterior superior iliac spine. The radiotracer was always detectable by scintigram in the lungs when the shunt was patent. In case of malfunction, by contrast, the radioactivity was either restricted to the venous tube or confined below the diaphragm for at least 4 hr. In the presence of complete obstruction, whereas the tube was not visualized after peritoneal injection, it was outlined by direct injection of 2 mCi of Tc-99m albumin microspheres into its subcutaneous tract, where it crossed the 12th rib, immediately above the valve. This technique sufficed to establish whether the site of obstruction was at the valve or in the tubing itself. In one patient, poor visualization of the tube and a delayed image of the lungs was caused by partial occlusion of the valve with fibrinoid debris. This radiotracer method proved simple, quick, and led to an immediate selective replacement when the shunt was not patent. Therefore, the use of this test is recommended for a definitive diagnosis, since there were neither false negatives nor false positives. No complications such as embolism or bacterial infection were encountered with Tc-99m human albumin microspheres, which are excellent tracers.