Responsive neurostimulation in pediatric epilepsy: a systematic review and individual patient meta-analysis supplemented by a single institution case series in 105 aggregated patients.

PURPOSE: To assess responsive neurostimulation (RNS) efficacy in pediatric patients with drug-resistant epilepsy, comparing response (≥ 50% reduction in seizure frequency) rates between patients with two or fewer seizure foci and those with multifocal or generalized epilepsy. This study seeks to address the gap in knowledge regarding RNS effectiveness in pediatric populations. METHODS: A systematic review and meta-analysis included data from PubMed, Embase, and Web of Science through November 2023, including 17 retrospective studies and a case series of 24 patients from our practice for a total of 105 aggregated patients. The inclusion criteria of patients were age ≤ 18 and diagnosis of DRE. Exclusion criteria were nonhuman subjects and cases where RNS was not utilized to treat DRE. Study inclusion criteria were detailing the use of RNS and comparing patients with ≤ 2 foci with other focalities. Study exclusion criteria were failure to specify RNS lead placement or type of epilepsy. The risk of bias was assessed using the ROBINS-I tool for all non-randomized studies. Effect sizes and variances were aggregated to provide a comprehensive measure of RNS efficacy, and heterogeneity among the studies was assessed using I2 statistics and Cochran's Q test to evaluate the consistency of the findings. Statistical analyses were conducted using IBM SPSS. We analyzed demographics, epilepsy history, treatment outcomes, and RNS details using descriptive and inferential statistics, including Wilcoxon-Mann-Whitney, Fisher's exact, and chi-squared tests. This systematic review was not registered. RESULTS: Seventeen retrospective studies and a single-institution case series, encompassing 105 pediatric patients, were analyzed. Effect sizes and confidence intervals were calculated to quantify treatment effects. Analyses revealed that RNS reduces seizure frequency across a spectrum of pediatric epilepsy syndromes, irrespective of the seizures' focal, multifocal, or generalized origins. The effectiveness of RNS was not influenced by the patient's sex, age at epilepsy onset, or presence of neurological and psychiatric comorbidities. Prior vagus nerve stimulation surgery and the presence of an epileptic syndrome were factors associated with a lower likelihood of near-complete seizure remission with RNS, underscoring the complexities of treating patients with generalized epilepsies or previous interventional failures. The necessity of further research into individualized surgical strategies for patients was underscored by the mixed results of comparisons of electrode characteristics with responder rates. Limitations of our study include its reliance on retrospective studies, which introduces potential bias and limits the ability to infer causality. DISCUSSION: RNS is a safe and effective treatment in pediatric patients with DRE across demographic, comorbidity, and focality variability. FDA age and focality restrictions, along with patient and physician hesitancy, may be limiting the potential for effective treatment of pediatric DRE with RNS. Prospective randomized trials are recommended to validate these findings.

Iron catalyzed diastereoselective hydrogenation of chiral imines.

Cyclopentadienone-based iron complexes were used for the first time to successfully catalyze the diastereoselective hydrogenation of enantiopure imines. Chiral amines, including valuable biologically active products, were obtained often as enantiomerically pure compounds. Computational studies helped to elucidate the chemical and stereochemical aspects of the iron-catalyzed reaction.

Surgical Management of Aneurysmal Hematomas: Prognostic Factors and Outcome.

From 1991 until 2013, 304 patients with intracranial hematomas from aneurysmal rupture were managed surgically in our department, constituting 17 % of all patients with aneurysmal rupture. Of them, 242 patents presented with isolated intracerebral hematomas (in 69 cases associated with significant intraventricular hemorrhage), 50 patients presented with combined intracerebral and subdural hematomas (in 11 cases associated with significant intraventricular hemorrhage), and 12 presented with an isolated subdural hematoma. The surgical procedure consisted of simultaneous clipping of the aneurysm and evacuation of the hematoma in all cases. After surgery, 16 patients (5 %) submitted to an additional decompressive hemicraniectomy, and 66 patients (21 %) submitted to a ventriculo-peritoneal shunt. Clinical outcomes were assessed at discharge and at 6 months, using the modified Rankin Scale (mRS); a favorable outcome (mRS 0-2) was observed in 10 % of the cases at discharge, increasing to 31 % at 6 months; 6-month mortality was 40 %. Applying uni- and multivariate analysis, the following risk factors were associated with a significantly worse outcome: age >60; preoperative Hunt-Hess grades IV-V; pupillary mydriasis (only on univariate); midline shift >10 mm; hematoma volume >30 cc; and the presence of hemocephalus (i.e., packed intraventricular hemorrhage). Based on these results, an aggressive surgical treatment should be adopted for most cases with aneurysmal hematomas, excluding patients with bilateral mydriasis persisting after rescue therapy.

Surgical exclusion of unruptured middle cerebral artery aneurysms: experience of 126 cases.

A group of 126 surgical patients with 143 unruptured MCA aneurysms was evaluated in order to determine the risks of treatment and possible adjuncts for safer surgery. The precise location and size of the aneurysms were determined in each case; 21 aneurysms were located on the M1 tract, 109 on the main division - which consisted of more than two branches in 10 cases and was proximally located in 12 cases - and 13 were distal; 36 aneurysms were small (<7 mm), 90 standard, and 17 large or giant (>15 mm); 45 patients harbored multiple aneurysms (12 on the ipsilateral MCA). The aneurysms were excluded by clip in most cases, with the assistance of intraoperative flowmetry in 78 patients. Temporary proximal vessel occlusion was used in 57 patients (>10 min in 8 cases), without significant effects on radiological or clinical outcome. After surgery, newly occurring minor deficits were observed in 5 patients and significant deficits in 4; one patient died from an intractable coagulopathy. The low rate (3.9 %) of unfavorable results (modified Rankin Score > 2) linked to surgery justifies serious consideration for treatment in these patients, especially when facing the high disability rate after the rupture of aneurysms in this anatomical location.

Surgery after embolization of cerebral arterio-venous malformation: experience of 123 cases.

A group of 123 patients with large or critically located arterio-venous malformations (AVMs), operated on between 1990 and 2011 and who underwent preoperative embolization, was assessed in order to clarify the risks of this combined treatment. AVM location, volume, and Spetzler's grade were assessed in each case; AVM volume was over 20 cm(3) in 49 % of the cases; Spetzler's grade was 3 or above in 76 % of the cases (with 34 cases in grades 4-5). A mean of 2.3 embolization procedures per patient were carried out, using bucrylate and, more recently, Onyx and/or Glubran; a 4.5 % procedure-related complication rate was observed. Complications occurring after surgery were classified as hemorrhagic (16 cases, 8 requiring surgical evacuation) or ischemic (4 cases); hemorrhagic complications were more common for AVMs with volumes >20 cm(3) and/or deep feeders. Surgery-related unfavorable results (modified Rankin Score > 2) were observed in 6 % of patients in Spetzler's grade 3, and in 20-25 % of patients in grades 4-5. More recently, a triple treatment (radiosurgery + embolization + surgery) allowed for obtaining favorable results (mRS 0-2) in all patients. It has been concluded that a combined treatment with embolization and surgery constitutes a reasonable choice for complex cerebral AVMs; the association of radiosurgery may improve the patients outcome.

Compensatory renal growth in children with unilateral renal tumor treated by nephron-sparing surgery or nephrectomy.

INTRODUCTION: In children with an unilateral renal tumor, nephron-sparing surgery (NSS) results in a more adequate renal function adaptation compared to nephrectomy. In the present study, we investigated whether nephron-sparing surgery is followed by a different renal structure adaptation compared to nephrectomy. METHODS: Sixteen patients with unilateral renal tumor treated by nephrectomy (Group 1) and 10 treated by nephron-sparing surgery (Group 2) were enrolled in the study. Kidney volume was estimated by ultrasonography, using the formula for a prolate ellipsoid. Kidney volume was adjusted to the patient's weight and kidney laterality and expressed as a percentage of the expected volume of two kidneys in a healthy child. Total kidney volume (TKV) corresponded to the volume of the contralateral kidney in Group 1 patients, and to the volume of contralateral kidney + kidney remnant in Group 2 patients. Renal function was evaluated by serum creatinine values adjusted for sex and age and expressed as standard deviation scores (SDS). RESULTS: Group 2 patients presented with a greater indexed TKV compared to Group 1 patients, (97.4 +/- 18.8 % vs. 77.0 +/- 17.7 %; p = 0.005). Indexed TKV below the reference range for healthy controls with two kidneys was found in 4 of 10 Group 2 patients vs. 14 of 16 Group 1 patients (p = 0.017). In both patient groups, correlation analysis of indexed TKV and creatinine SDS showed a negative correlation (r = - 0.47; p = 0.01). CONCLUSION: In children with unilateral renal tumor, NSS is followed by a more adequate compensatory restoration of TKV compared with nephrectomy.

Anti-fibroblast antibodies detected by cell-based ELISA in systemic sclerosis enhance the collagenolytic activity and matrix metalloproteinase-1 production in dermal fibroblasts.

OBJECTIVES: Antibodies binding to the surface of fibroblasts (anti-fibroblast antibodies: AFA) have been described in systemic sclerosis (SSc). We aimed to assess the effect of AFA on extracellular matrix (ECM) turnover and whether AFA were associated with anti-topoisomerase-I antibody. METHODS: IgG were purified from AFA-positive and AFA-negative sera selected within 20 SSc and 20 healthy individuals, and tested on normal dermal fibroblasts, at protein and mRNA level, for their capacity to induce collagen deposition or degradation. RESULTS: Fibroblasts stimulated with AFA-positive but not with AFA-negative and control IgG showed an increased capacity to digest collagen matrix and produce metalloproteinase-1 (MMP-1) while their production of total collagen, type I collagen and tissue inhibitor of metalloproteinase-1 (TIMP-1) was unaffected. The steady-state mRNA levels of MMP-1, COL1A1 and TIMP-1 paralleled the protein levels. AFA-positive IgG did not induce Smad 2/3 phosphorylation, indicating that this transforming growth factor-beta signalling pathway was not involved. IL-1 and tumour necrosis factor (TNF) neutralization did not reverse the enhanced production of MMP-1, suggesting a direct effect of AFA on fibroblasts. Finally, anti-topoisomerase-I antibodies were present in 11 of 12 AFA-negative IgG, and an anti-topoisomerase-I monoclonal antibody failed to enhance MMP-1 production, thus indicating a lack of correlation between AFA and anti-topoisomerase-I antibody. CONCLUSIONS: These results indicate that SSc antibodies binding to fibroblasts enhance matrix degradation and MMP production events that may favour inflammation but do not directly impact on fibrosis development.

[Digital ulcers in a cohort of 333 scleroderma patients]. / Ulcere digitali in una coorte di 333 pazienti sclerodermici.

Digital ulcers (DU) at the hands are one of the more frequent and severe complications in systemic sclerosis. Data on their prevalence and distribution in the different subsets of disease are variable in the literature. We studied the frequency of DU in a cohort of 333 scleroderma patients followed in the last 10 years in our Unit. DU have been recorded in 133 patients (39,9%), more frequently in males, in patients with cutaneous diffuse form of disease and in patients with anti-Scl70 ANA specificity. Complications of DU have been observed in 12,3% of cases. Surgery of the hands has been required in 8,7% of patients. The more effective treatment of DU are i.v. prostanoids, performed usually in day hospital, with high costs for the National Health Service. Recently the efficacy of bosentan, an oral receptor antagonist of endothelin, has been demonstrated, thus opening new perspectives in the treatment of DU in systemic sclerosis.

[Tenosynovitis of the ankles as onset of sarcoidosis in a patient with ulcerative colitis]. / Tenosinovite delle caviglie come segno d'esordio di sarcoidosi in un paziente con rettocolite ulcerosa.

Arthritis and tenosynovitis are frequently reported as complications of inflammatory bowel diseases. About 10% of patients with ulcerative colitis presents articular inflammation, usually in the phases of activity of intestinal disease. Tenosynovitis is also a frequent complication of ulcerative colitis. We describe here a case of tenosynovitis of both ankles occurring in a patient affected by ulcerative colitis not in active phase. Chest X-ray and TC showed hilar lymph node enlargement and transbronchial biopsy confirmed the diagnosis of sarcoidosis. In this disease tenosynovitis is very rare, unlike arthritis that is rather common. In conclusion we observed a case of ankle bilateral tenosynovitis as onset manifestation of sarcoidosis.

Anti-inflammatory effect of mud-bath applications on adjuvant arthritis in rats.

OBJECTIVE: The real effects of mud-bath applications on the inflammatory process are still not clarified. We studied these effects on rat adjuvant-induced arthritis. METHODS: Arthritis was induced in 30 rats by subplantar injection of Freund's complete adjuvant (FCA) into the right hind paw. Ten days after FCA injection, the rats were randomized in 3 groups of 10 each: the first one was submitted to a cycle of mud-bath applications, the second one was treated with indomethacin, the third one received only saline per os (control group). The paw volume, measured by plethysmometry, and the serum levels of TNFalpha and IL-1beta were considered as evaluation parameters. RESULTS: FCA injection caused a progressive enhancement of paw volume and a rapid increase of TNFalpha and IL-1beta serum levels. After the randomization, mud-bath applications reduced inflammation and at the end of the treatment the paw volume and the TNFa and IL-1beta serum levels were significantly tapered in comparison to the controls (p < 0.01). CONCLUSION: The results of the study suggest an anti-inflammatory effect of mud-bath applications on adjuvant arthritis in rats. These results could explain the beneficial effects of thermal treatments observed in some inflammatory rheumatic diseases.

Dystrophic phenotype of canine X-linked muscular dystrophy is mitigated by adenovirus-mediated utrophin gene transfer.

Utrophin is highly homologous and structurally similar to dystrophin, and in gene delivery experiments in mdx mice was able to functionally replace dystrophin. We performed mini-utrophin gene transfer in Golden Retriever dogs with canine muscular dystrophy (CXMD). Unlike the mouse model, the clinicopathological phenotype of CXMD is similar to that of Duchenne muscular dystrophy (DMD). We injected an adenoviral vector expressing a synthetic utrophin into tibialis anterior muscles of newborn dogs affected with CXMD and examined transgene expression by RNA and protein analysis at 10, 30 and 60 days postinjection in cyclosporin-treated and -untreated animals. Immunosuppression by cyclosporin was required to mitigate the immune response to viral and transgene antigens. RT-PCR analysis showed the presence of the exogenous transcript in the muscle of cyclosporin-treated and -untreated animals. The transgenic utrophin was efficiently expressed at the extrajunctional membrane in immunosuppressed dogs and this expression was stable for at least 60 days. We found reduced fibrosis and increased expression of dystrophin-associated proteins (DAPs) in association with muscle areas expressing the utrophin minigene, indicating that mini-utrophin can functionally compensate for lack of dystrophin in injected muscles. For this reason, utrophin transfer to dystrophin-deficient muscle appears as a promising therapeutic approach to DMD.

Radial artery pseudoaneurysm successfully treated by compression bandage.

In children, surgery for radial artery pseudoaneurysm (PA) may be followed by growth retardation of the hand because of inadequate blood flow. We believe this is the first report of a child with PA of the radial artery cured by compression bandage. Conservative management is a safe and valuable initial treatment option for uncomplicated radial PA.

[Prevalence and clinical features of fibromyalgia in systemic lupus erythematosus, systemic sclerosis and Sjögren's syndrome]. / Prevalenza e caratteristiche cliniche della fibromialgia nelle connettiviti maggiori: lupus eritematoso sistemico, sclerosi sistemica e sindrome di Sjögren primitiva.

BACKGROUND: We studied the prevalence of fibromyalgia in 3 different groups of patients affected respectively with systemic lupus erythematosus, systemic sclerosis (scleroderma) and primary Sjögren's syndrome. The typical fibromyalgia findings encountered in these diseases were examined. METHODS: We enrolled 250 consecutive outpatients: 100 with systemic lupus erythematosus, 50 with systemic sclerosis, 100 with primary Sjögren's syndrome and 2 control groups (30 healthy subjects and 75 patients with primary fibromyalgia). Fibromyalgia features were evaluated by algometry, VAS for pain, Mc Gill Pain Questionnaire and Fibromyalgia Impact Questionnaire. RESULTS: Fibromyalgia has been found in 1 case (1%) with systemic lupus erythematosus, 1 case with systemic sclerosis (2%), 22 cases (22%) with primary Sjögren's syndrome and in 1 (3.3%) of the healthy controls. The number of tender points was significantly higher (p<0.01) in the patients with Sjögren's syndrome in comparison with the other groups. Fibromyalgic findings were similar in the patients with primary fibromyalgia and Sjögren's syndrome with fibromyalgia, unless for both poor sleep and low algometric thresholds which were more frequently found in primary fibromyalgia (respectively p<0.001 and p=0.05). CONCLUSIONS: Our study suggests that fibromyalgia is relatively frequent in primary Sjögren's syndrome, while in systemic lupus and systemic sclerosis its prevalence is not different from that found in the healthy controls. Typical fibromyalgia findings, except algometric values, were similar between the cases with Sjögren's syndrome plus fibromyalgia and fibromyalgia alone.

Respiratory status of infants with esophageal atresia.

In infants with esophageal atresia (EA), lung opacities on a chest radiograph (CXR) are usually considered the cause of respiratory distress (RD). However, in some instances signs of RD and CXR changes show no correlation. The aim of this study was to investigate the pathogenesis of RD in EA patients with a normal CXR. In 41 infants with EA, CXR findings were correlated with clinical manifestations and blood-gas analysis data. The degree of abnormal gas exchange was quantitated by the arterial/alveolar oxygen tension ratio (a-ARO2). Of the 41 infants, 39(95%) presented with RD. No lung opacities were found in 130 of 294 CXRs examined (44%). An a-ARO2 below 0.75 (lower limit of normal) was calculated in 215 of 247 arterial blood samples analyzed (87%). When a temporal correlation was established, RD with a clear CXR was characterized by signs of extra- and intrathoracic airway obstruction, often associated with an a-ARO2 below 0.75. The degree of hypoxemia was greater than the degree of hypercapnia. We conclude that in infants with EA, RD with a clear CXR is related to both tracheomalacia and upper-airway obstruction that may cause miliary atelectasis not detected by conventional CXR with intrapulmonary shunting and hypoxemia.

Poly(ethylene glycol)-supported bisoxazolines as ligands for catalytic enantioselective synthesis.

Two chiral bisoxazolines (box) supported on a modified poly(ethylene glycol) (PEG) have been prepared by a reaction sequence that involved formation of the properly functionalized box and their attachment to the polymer matrix by means of a spacer and a linker. The solubility properties of PEG allowed use of the supported box as ligands in some catalytic asymmetric transformations carried out under homogeneous conditions and to recover the ligands as if bound to an insoluble support. When the supported box were employed in combination with Cu(II) salts in the Diels-Alder cycloaddition between cyclopentadiene and N-acryloyloxazolidinone, low levels of enantioselectivity were observed (up to 45% ee). Much better results were obtained in the cyclopropanation of styrenes carried out in the presence of CuOTf (up to 93% ee) and in the ene-reaction between alpha-methylstyrene or methylenecyclohexane and ethylglyoxalate (up to 95% ee). One of the ligands, readily recovered by precipitation and filtration, was recycled two times in the ene-reaction with marginal loss in the catalytic activity and very limited erosion of the enantioselectivity.

Nephron-sparing surgery for unilateral primary renal tumor in children.

PURPOSE: Definition of the role of nephron-sparing surgery (NSS) in the treatment of children with primary unilateral renal tumor (URT). METHODS: Between January 1992 and June 2000, 28 children with URT were admitted to our surgical unit. Criteria for selection of patients eligible for NSS were at least 50% of affected kidney preservable and stage I at surgery (frozen section biopsies from regional lymph nodes, perirenal fat, and surrounding renal parenchyma). Preoperative 2-drug chemotherapy was given to all patients more than 6 months of age. Between 1992 and 1995, 3-drug chemotherapy was used after NSS. Thereafter, following NSS, 2-drug chemotherapy was given if no microscopic residual disease was found on final histologic examination. RESULTS: NSS was feasible in 10 of 28 children (35%). Enucleation of 6 tumors (1 metachronous) was performed in 5 patients. NSS was elective in 5 patients, mandatory in 3 patients (1 with aniridia and genitourinary anomalies, 1 with chronic glomerulonephritis, 1 with bilateral hyperplastic nephroblastomatosis), and advisable in 2 patients (1 with familial vesicoureteric reflux and 1 with cystic nephroma). Seven children had standard histology nephroblastoma, 1 highly differentiated epithelial type nephroblastoma, 1 oncocytoma, and 1 cystic nephroma. The only post-NSS complication was macroscopic hematuria in 1 patient. None of the patients had a relapse. All children are alive and disease free with good functioning of the affected kidney after NSS, at a mean follow-up of 40.7 months (range, 2 to 100 months). CONCLUSION: NSS should be considered in selected children with URT, especially in patients with increased risk for metachronous tumor or renal disease, and in patients with benign or low-grade malignant URT.

A poly(ethylene glycol)-supported quaternary ammonium salt: An efficient, recoverable, and recyclable phase-transfer catalyst

A quaternary ammonium salt readily immobilized on a soluble poly(ethylene glycol) polymer support efficiently catalyzes different reactions carried out under phase-transfer catalysis conditions; the catalyst, easily recovered by precipitation and filtration, shows no appreciable loss of activity when recycled three times.

Soluble-polymer-supported synthesis of beta-lactams on a modified poly(ethylene glycol)

A modified poly(ethylene glycol) (PEG) has been developed for the soluble-polymer-supported synthesis of beta-lactams. The monomethylether of PEG (MeOPEG) with an average M(W) of 5000 was used as the support, a 4-(3-propyl)phenyl residue as the spacer, and a 4-oxyphenylamino group as the moiety with the reactive functionality. From this modified PEG representative aromatic, heteroaromatic, unsaturated, and aliphatic imines were obtained in high yields by different procedures. The polymer-supported imines were then employed to prepare several beta-lactams by enolate/imine condensation and ketene/imine cycloaddition. Examples of the control of the absolute stereochemistry during the azetidinone ring formation are also reported. The reactions carried out on the polymer-bound imines showed a remarkable similarity to those performed on nonimmobilized imines, both in terms of yields and stereoselectivities. Removal of the beta-lactams from the polymer has also been accomplished to directly deliver the N-unsubstituted azetidinones.

Elective partial splenectomy in childhood.

BACKGROUND & PURPOSE: The indications and results of elective partial splenectomy in children remain uncertain. The aim of this study was to determine (1) the indications for elective partial splenectomy (EPS), (2) the extent of splenic resection, and (3) the complications of EPS. METHODS: Patients who underwent EPS from three centers over a 10-year period (1986 through 1996) were studied. Variables analyzed included clinical presentation and indications for EPS, extent of resection performed, perioperative transfusions, and complications. Postoperatively, splenic viability was determined by regular Doppler ultrasound scan and splenic function on peripheral blood film analysis. RESULTS: EPS was attempted in 12 children for various conditions: giant epithelial cyst (n = 6), hypersplenism and metabolic disease (n = 4), pseudotumor (n = 1), and abscess (n = 1). One procedure was converted to total splenectomy because of thin splenic tissue around an infected giant cyst. No child required transfusion for splenic bleeding. There were no postoperative complications or deaths. Only 7 of the 12 children received prophylactic preoperative immunisation. In the 11 successful cases splenic remnant viability remains confirmed by ultrasound scan and normal blood film. There has been no significant splenic regrowth or recurrent hypersplenism in the four children with metabolic disorders. CONCLUSIONS: EPS is suitable for benign splenic conditions and can be performed without major blood loss. Preoperative vaccination is advisable. Up to 95% of the spleen can be safely removed, basing the blood supply of the residual spleen tissue on peripheral polar vessels, with adequate postoperative function.