Role of folic acid depletion on homocysteine serum level inchildren and adolescents with epilepsy and different MTHFR C677T genotypes.

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. An elevated total plasma Hcy concentration (tHcy) is a risk factor for vascular disease. The present study aimed to assess the role of antiepileptic drugs (AEDs) and C677T methylenetetrahydrofolate (MTHFR) polymorphisms on tHcy in pediatric patients with epilepsy treated for at least 6 months with various treatment regimens protocols including the newer AEDs. The study group was recruited from children and adolescents with epilepsy followed up in the Child Neuropsychiatry Clinic of the Second University of Naples, between January 2007 and March 2008. Inclusion criteria were: (1) patients with epilepsy, treated with one or more anticonvulsant drugs for at least 6 months; (2) age between 2 and 16 years. Plasma tHcy concentrations were considered elevated when they exceeded 10.4 mmol/L, and folate concentrations <3 ng/mL were considered deficient. Serum vitamin B12 levels were considered normal between 230 and 1200 pg/mL. The study group was composed of 78 patients (35 males, 43 females), aged between 3 and 15 years (mean 8.9 years). Thirtyfive patients were taking AED monotherapy, 43 polytherapy. Sixty-three healthy sex- and age-matched children and adolescents served as controls. The mean tHcy value in the patient group was higher than the mean value in the control group (12.11 7.68 mmol/L vs 7.4 4.01 mmol/L; p < 0.01). DNA analysis for the MTHFR C677T polymorphism showed the CT genotype in 46%, CC in 35% and TT in 17.8% of cases. Decreased folic acid serum levels significantly correlated with increased tHcy levels (p < 0.003). Female sex was a less significant risk factor for increased tHcy levels (p = 0.039). Our study confirms the association between hyperhomocysteinemia and epilepsy. The elevation of tHcy is essentially related to low folate levels. Correction of poor folate status, through supplementation, remains the most effective approach to normalize tHcy levels in patients on AED mono- or polytherapy

12-months prospective Pentraxin-3 and metabolomic evaluation in multiple sclerosis patients treated with glatiramer acetate

Background: Pentraxin-3 (PTX-3) is involved in acute immunological responses and it is a pro-inflammatory protein and a novel biomarker of inflammatory diseases. It is demonstrated that PTX-3 is higher in cerebrospinal fluid (CSF) of aggressive Multiple Sclerosis (MS). Metabolomics, the identification of small endogenous molecules, offers a molecular profile of MS. Glatiramer acetate (GA) is a widely used treatment for (MS) but its mechanism of action is not completely defined. The aim of our study is to analyze PTX-3 and metabolomic profile in MS patients compared to controls and to investigate the effect of GA on PXT-3 and metabolic molecules during treatment in responder and not responder MS patients. Methods: 28 unrelated MS patients and 27 age-and sex-matched controls were recruited. In serum, PTX-3 levels were measured by ELISA and Metabolomic panel was evaluated trough Nuclear Magnetic Resonance (NMR). According to clinical practice patients started GA treatment; PTX-3 and metabolomic identification were performed before and during treatment. Responders to treatment were identified if no evidence of instrumental, clinical relapses and disability progression (NEDA) occurred during follow up. Results: Serum PTX-3 levels were higher in MS patients compared to matched controls (7,85 ± 2,19 vs 6,20 ± 1,63 ng/ml) (p = 0,03); metabolomic evaluation shows higher levels of lactate and lower levels of valine, tyrosine and tryptophan in MS patients compared to controls. During therapy, PTX-3 levels have been reduced statistically significant (p = 0,001) at six months and one year of treatment. After one year, of the twenty patients that completed the study, 55% were considered fully responders to treatment; in these patients the mean reduction of PTX-3 at one year was higher respect to not responders (−3,82 ± 1,24 ng/ml vs −2,32 ± 1,03 ng/ml p = 0,02) and we observed a higher reduction of lactate, tyrosine and hypoxanthine and an increase of hydroxyproline and ADP as well as of three oxidative phosphorylation markers, citrulline, ornithine and tryptophan approaching the metabolic profile of healthy subjects. Discussion and conclusions: We demonstrated a metabolomic imbalance with mitochondrial dysfunction detected by higher levels of lactate and lower levels of tryptophan, tyrosine and valine in MS patients compared to healthy controls. The reduction of PTX-3 levels and the restoring of mitochondrial function, reducing oxidative stress by GA, allows to identify responder patients. Further and larger studies are needed to understand the predictive role of PTX-3 and metabolomic pattern in the identification of responder patients to GA

Bidirectional barbed suture in total laparoscopic hysterectomy and lymph node dissection for endometrial cancer: technical evaluation and 1-year follow-up of 61 patients

Objective: This randomized clinical study compared the feasibility and safety of the shortest suture for bidirectional knotless barbed versus standard sutures, with either extracorporeal or intracorporeal knots, for vaginal cuff closure following total laparoscopic hysterectomy (TLH) and lymph node dissection for early endometrial cancer. Subjects and Methods: The study design was Canadian Task Force Classification I. In tertiary-care university-based teaching hospitals, 61 women underwent TLH and lymph node dissection. In accord with randomization, the vaginal cuff in TLH was closed with either extracorporeal or intracorporeal knots (1-Monocryl®; Ethicon Inc., Somerville, NJ) and a bidirectional knotless barbed suture (0-Quill™; Angiotech Pharmaceuticals, Inc., Vancouver, BC, Canada). All patients were evaluated at 3-month, 6-month, and 1-year follow-up. Results: Time required to suture was significantly lower in the group treated with bidirectional suture than in groups with traditional sutures (P<.001). No significant difference was observed in the operative time between the study groups. The degree of surgical difficulty was significantly lower in the bidirectional barbed suture group than in the other groups. At 1-year follow-up all patients presented no wound dehiscence, no bleeding, dyspareunia, and other potential major complications such as ureteric, bladder, or bowel injury. Conclusions: Use of a barbed suture reduces the time required to repair the vaginal cuff during TLH. At follow-up of patients, carried out 3 months, 6 months, and 1 year after the surgery, no wound dehiscence, no bleeding, or no other potential major surgical complications had occurre

Physical activity regulates tnfα and il-6 expression to counteract inflammation in cystic fibrosis patients

Background: Cystic fibrosis (CF) is one of the most common inherited diseases. It is characterised by a severe decline in pulmonary function associated with metabolic perturbations and an increased production of inflammatory cytokines. The key role of physical activity (PA) in improving the health status of CF patients and reducing lung function decline has recently been demonstrated. This study evaluated interleukin-6 (IL-6) and tumour necrosis factor α (TNFα) expression in two subgroups of CF patients classified based on PA. Methods: We selected 85 CF patients; half of them regularly undertook supervised PA in the three years leading up to the study and half of them were not physically active. Patients were analysed for serum IL-6 and TNFα levels using enzyme-linked immunosorbent assays. Results: We found that the expression levels of IL-6 and TNFα differed in terms of their regulation by PA. In particular, TNFα levels negatively correlated with FEV1% decrease/year and FEV1% decrease (p = 0.023 and p = 0.02, respectively), and positively correlated with serum fasting glucose (p = 0.019) in PA CF patients. In contrast, in the NPA subgroup, TNFα levels were positively correlated with IL-6 (p = 0.001) and negatively correlated with adiponectin (p = 0.000). In addition, multiple logistic regression analysis confirmed that PA is an independent modulator of the inflammatory state. Conclusions: PA modulates inflammatory processes in CF patients by regulating the secretion of pro-inflammatory cytokines and thus ameliorating lung function. Our data show that PA is a useful complementary strategy in the management of CF and that TNFα may be a marker of these effects of PA

RenalGuard system in high-risk patients for contrast-induced acute kidney injury.

BACKGROUND: High urine flow rate (UFR) has been suggested as a target for effective prevention of contrast-induced acute kidney injury (CI-AKI). The RenalGuard therapy (saline infusion plus furosemide controlled by the RenalGuard system) facilitates the achievement of this target. METHODS: Four hundred consecutive patients with an estimated glomerular filtration rate ≤30 mL/min per 1.73 m(2) and/or a high predicted risk (according to the Mehran score ≥11 and/or the Gurm score >7%) treated by the RenalGuard therapy were analyzed. The primary end points were (1) the relationship between CI-AKI and UFR during preprocedural, intraprocedural, and postprocedural phases of the RenalGuard therapy and (2) the rate of acute pulmonary edema and impairment in electrolytes balance. RESULTS: Urine flow rate was significantly lower in the patients with CI-AKI in the preprocedural phase (208 ± 117 vs 283 ± 160 mL/h, P 0.32 mg/kg (HR 5.03, 95% CI 2.33-10.87, P < .001) were independent predictors of CI-AKI. Pulmonary edema occurred in 4 patients (1%). Potassium replacement was required in 16 patients (4%). No patients developed severe hypomagnesemia, hyponatremia, or hypernatremia. CONCLUSIONS: RenalGuard therapy is safe and effective in reaching high UFR. Mean intraprocedural UFR ≥450 mL/h should be the target for optimal CI-AKI prevention

Successful management of peri-implantitis around short and ultrashort single-crown implants: a case series with a 3-year follow-up

Introduction and Aim. In case of peri-implantitis, resective surgery is contraindicated for short and ultrashort implants, limiting the treatment options to regenerative surgery or to implant removal. 'is retrospective case series presents the clinical and radiographic outcomes of a surgical regenerative procedure to treat peri-implantitis around short and ultrashort implants. Materials and Methods. The study is a retrospective evaluation of patients suffering from peri-implantitis and those who underwent access flap surgery, concomitant chemical and mechanical decontamination of implant surface, and bone grafting using a self-hardening mixture of bone substitutes and biphasic calcium sulfate. No membranes were applied to cover the grafting material, and primary tension-free closure was achieved. The retrospective protocol was reviewed and approved by the Ethics Committee for Clinical Sperimentation (CESC) of Verona and Rovigo, Italy (based in the University of Verona) (Prog. 1863CESC. Date of approval: 2018-07-04). Results. 15 patients (17 implants) have been diagnosed with peri-implantitis after a mean follow-up of 24 months after loading. Implant length was between 5 and 8 mm. 8 patients (10 implants) had a history of periodontitis. At baseline, the mean PD (probing pocket dept) at the deepest site was 8.12 mm, with an average mBI (modified bleeding index) of 2.35 and a mean BD (bone defect depth) of 3.04 mm. At the 3-year follow-up, the CSR was 100%, the mean mBI was 0.88 (average reduction: - 1.47), the mean PD was 3.35 mm (mean PD reduction: 4.77 mm), and the mean bone defect was reduced by 1.74 mm, with a mean bone fill of 55%. Conclusions. The results of the present case series suggest that if accurate surface decontamination is achieved, high survival rate and good clinical and radiographic results can be obtained after 3 years. However, only the histological examination could confirm the growth of new bone in direct contact with the implant surface or if the grafted material only fills the space left by the peri-implant defect

Cd19 cell count at baseline predicts b cell repopulation at 6 and 12 months in multiple sclerosis patients treated with ocrelizumab

Background: The kinetics of B cell repopulation in MS patients treated with Ocrelizumab is highly variable, suggesting that a fixed dosage and time scheduling might be not optimal. We aimed to investigate whether B cell repopulation kinetics influences clinical and radiological outcomes and whether circulating immune asset at baseline affects B cell repopulation kinetics. Methods: 218 MS patients treated with Ocrelizumab were included. Every six months we collected data on clinical and magnetic resonance imaging (MRI) activity and lymphocyte subsets at baseline. According to B cell counts at six and twelve months, we identified two groups of patients, those with fast repopulation rate (FR) and those with slow repopulation rate (SR). Results: A significant reduction in clinical and radiological activity was found. One hundred fifty-five patients had complete data and received at least three treatment cycles (twelve-month follow-up). After six months, the FR patients were 41/155 (26.45%) and 10/41 (29.27%) remained non-depleted after twelve months. FR patients showed a significantly higher percentage of active MRI scan at twelve months (17.39% vs. 2.53%; p = 0,008). Furthermore, FR patients had a higher baseline B cell count compared to patients with an SR (p = 0.02 and p = 0.002, at the six-and twelve-month follow-ups, respectively). Conclusion: A considerable proportion of MS patients did not achieve a complete CD19 cell depletion and these patients had a higher baseline CD19 cell count. These findings, together with the higher MRI activity found in FR patients, suggest that the Ocrelizumab dosage could be tailored depending on CD19 cell counts at baseline in order to achieve complete disease control in all patients

Diffuse glioblastoma resembling acute hemorrhagic leukoencephalitis

We report the case of a young man with sudden onset of diplopia after an upper respiratory tract infection. Based on the first radiological findings acute hemorrhagic leukoencephalitis, a variant of acute disseminated encephalomyelitis, was suspected and treatment with high dose intravenous dexamethasone was started but it was stopped for intolerance. The patient clinically worsened, developing gait instability, ataxia and ophthalmoplegia; brain MRI performed 20 days later showed severe progression of the disease with subependymal dissemination. After brain biopsy of the right temporal lesion the histological diagnosis was glioblastoma. These findings suggest that MRI features of acute hemorrhagic leukoencephalitis may dissimulate the diagnosis of diffuse glioma/glioblastoma. This case underscores the importance of considering diffuse glioma in the differential diagnosis of atypical signs and symptoms of acute hemorrhagic leukoencephalitis and underlines the relevant role of integrating neuroradiologic findings with neuropathology