Cenobamate and Clobazam Combination as Personalized Medicine in Autoimmune-Associated Epilepsy With Anti-Gad65 Antibodies.

BACKGROUND AND OBJECTIVES: Autoimmune-associated epilepsy (AAE) with antiglutamic acid decarboxylase 65 (GAD65) antibodies is considered a T-cell-mediated encephalitis that evolves to drug-resistant epilepsy. We do not have an effective therapeutic strategy for these patients. Because the GAD enzyme is primarily responsible for the conversion of glutamate to GABA, the mechanism of epileptogenesis in this condition predicts decreased levels of GABA content in synaptic vesicles. Cenobamate (CNB) acts as a positive allosteric modulator at synaptic and extra synaptic GABAA receptors, producing increased inhibitory neurotransmission in the brain. This mechanism could be especially beneficial in AAE with anti-GAD65 antibodies because it would be able to correct the imbalance due to the GABAergic stimulation deficit in postsynaptic neurons. METHODS: We recruit a retrospective multicentric consecutive case series of AAE with anti-GAD65 antibodies from 5 epilepsy units in Spain who have received treatment with CNB. RESULTS: A total of 8 patients were recruited. This cohort of highly refractory patients have failed a mean of 9.50 (SD = 3.20) ASM without control of seizures for sustained periods of time. The average number of seizures per month during the previous 3 months before CNB treatment was 19.63 (SD = 17.03). After the introduction of CNB improvement was achieved in all our patients, with a median reduction in the number of seizures of 92.22% (interquartile range [IQR]: 57.25-98.75). The mean follow-up was 156.75 days (SD = 68.23). In patients with concomitant treatment with clobazam (CLB), the median percentage of seizure reduction was higher than those not taking CLB: 94.72% (IQR: 87.25-100) vs 41.50% (p = 0.044) and also higher than the control group of patients with refractory epilepsy not related to anti-GAD65 treated with the same combination: 94.72% (IQR: 87.25-100) vs 45.00% (IQR: 25.00-87.00) (p = 0.019). DISCUSSION: Treatment with the combination CNB + CLB could be a type of personalized medicine in patients with AAE with anti-GAD65. Our preliminary data will need to be endorsed with new prospective and controlled studies.

Is Onlay Polypropylene Mesh Repair an Available Option for Incisional Hernia Repair? A Retrospective Cohort Study.

Lately, incisional hernia repair (IHR) with onlay polypropylene mesh has been replaced by other surgical procedures. The aim of this study was to compare the complication and recurrence rate after onlay mesh repair and other surgical procedures for IHR. A retrospective cohort study of patients who underwent IHR in a single center was conducted. The data were obtained from electronic medical records. Patients who had been lost during follow-up were contacted for a visit in the clinic. Univariate and multivariate analysis was performed with Stata 13.0 to analyze the factors associated with postoperative complications and hernia recurrence. Between June 2004 and December 2015, 1078 patients underwent IHR in a single center. Onlay mesh repair was performed in 125 patients (11.6%). Other surgical procedures included Rives procedure (29.3%), sublay mesh repair (38.6%), intrabdominal mesh repair (17.1%), and primary closure (3.4%). After a mean follow-up of 2.8 years, 73 (7%) patients developed a recurrence. A higher percentage of complications were seen after onlay mesh repair than after other surgical procedures (22.4% vs 13.1%, P = 0.005). Nevertheless, recurrence was less frequent after onlay mesh repair (4.2% vs 7.1%, P = 0.241). Logistic regression discarded an association between onlay mesh repair and hernia recurrence or postoperative complications. Incisional hernia repair with onlay polypropylene mesh repair was not associated with a higher incidence of postoperative complications or recurrence rate. So, this procedure should not be discarded in selected patients presenting with incisional hernia.

Importance of mesh overlap on hernia recurrence after open umbilical hernia repair with bilayer prosthesis.

BACKGROUND: importance of mesh overlap on recurrence after open umbilical hernia repair has been poorly studied. METHODS: a retrospective cohort study was performed with patients who underwent open umbilical hernia repair with bilayer prosthesis between 2004 and 2015. RESULTS: 1538 patients were included. Fifty patients (3.3%) had a mesh overlap lower than 1 cm. After a mean follow-up of 4.1 years 53 patients (3.5%) developed a recurrence. Recurrence was associated with a mesh overlap smaller than 1 cm (10.2% vs. 3.3%, p = 0.010, OR = 3.3). In the logistic regression model an overlap smaller than 1 cm was not statistically associated with recurrence (OR = 2.5, p = 0.123). Female gender, postoperative complications and prosthesis size were associated with hernia recurrence. CONCLUSIONS: mesh overlap seems to be an important factor for hernia recurrence. A mesh overlap of at least 1 cm should be used until more studies are performed about this issue.

Clinical characteristics and outcome of Spanish patients with ANCA-associated vasculitides: Impact of the vasculitis type, ANCA specificity, and treatment on mortality and morbidity.

The aim of this study was to describe the clinical characteristics of ANCA-associated vasculitides (AAV) at presentation, in a wide cohort of Spanish patients, and to analyze the impact of the vasculitis type, ANCA specificity, prognostic factors, and treatments administered at diagnosis, in the outcome.A total of 450 patients diagnosed between January 1990 and January 2014 in 20 Hospitals from Spain were included. Altogether, 40.9% had granulomatosis with polyangiitis (GPA), 37.1% microscopic polyangiitis (MPA), and 22% eosinophilic granulomatosis with polyangiitis (EGPA). The mean age at diagnosis was 55.6 ±â€Š17.3 years, patients with MPA being significantly older (P < 0.001). Fever, arthralgia, weight loss, respiratory, and ear-nose-throat (ENT) symptoms, were the most common at disease onset. ANCAs tested positive in 86.4% of cases: 36.2% C-ANCA-PR3 and 50.2% P-ANCA-MPO. P-ANCA-MPO was significantly associated with an increased risk for renal disease (OR 2.6, P < 0.001) and alveolar hemorrhage (OR 2, P = 0.010), while C-ANCA-PR3 was significantly associated with an increased risk for ENT (OR 3.4, P < 0.001) and ocular involvement (OR 2.3, P = 0.002). All patients received corticosteroids (CS) and 74.9% cyclophosphamide (CYC). The median follow-up was 82 months (IQR 100.4). Over this period 39.9% of patients suffered bacterial infections and 14.6% opportunistic infections, both being most prevalent in patients with high-cumulated doses of CYC and CS (P < 0.001). Relapses were recorded in 36.4% of cases with a mean rate of 2.5 ±â€Š2.3, and were more frequent in patients with C-ANCA-PR3 (P = 0.012). The initial disease severity was significantly associated with mortality but not with the occurrence of relapses. One hundred twenty-nine (28.7%) patients (74 MPA, 41 GPA, 14 EGPA) died. The mean survival was 58 months (IQR 105) and was significantly lower for patients with MPA (P < 0.001). Factors independently related to death were renal involvement (P = 0.010), cardiac failure (P = 0.029) and age over 65 years old (P < 0.001) at disease onset, and bacterial infections (P < 0.001). An improved outcome with significant decrease in mortality and treatment-related morbidity was observed in patients diagnosed after 2000, and was related to the implementation of less toxic regimens adapted to the disease activity and stage, and a drastic reduction in the cumulated CYC and CS dose.

Umbilical Hernia Repair: Analysis After 934 Procedures.

There is a lack of consensus about the surgical management of umbilical hernias. The aim of this study is to analyze the medium-term results of 934 umbilical hernia repairs. In this study, 934 patients with an umbilical hernia underwent surgery between 2004 and 2010, 599 (64.1%) of which were evaluated at least one year after the surgery. Complications, recurrence, and the reoperation rate were analyzed. Complications were observed in 5.7 per cent of the patients. With a mean follow-up time of 35.5 months, recurrence and reoperation rates were 3.8 per cent and 4.7 per cent, respectively. A higher percentage of female patients (60.9 % vs 29 %, P = 0.001) and a longer follow-up time (47.4 vs 35 months, P = 0.037) were observed in patients who developed a recurrence. No significant differences were observed between complications and the reoperation rate in patients who underwent Ventralex(®) preperitoneal mesh reinforcement and suture repair; however, a trend toward a higher recurrence rate was observed in patients with suture repair (6.5 % vs 3.2 %, P = 0.082). Suture repair had lower recurrence and reoperation rates in patients with umbilical hernias less than 1 cm. Suture repair is an appropriate procedure for small umbilical hernias; however, for larger umbilical hernias, mesh reinforcement should be considered.

Randomised clinical trial: conventional Lichtenstein vs. hernioplasty with self-adhesive mesh in bilateral inguinal hernia surgery.

PURPOSE: To compare the results of conventional Lichtenstein hernioplasty with polypropylene mesh (PLP) with a lightweight self-adhesive mesh (Parietene Progrip®; Covidien, Dublin, Ireland) (PPG) used in patients with bilateral inguinal hernia. METHODS: Randomised clinical trial with 89 patients with a minimum follow-up of 1 year. Every patient had bilateral inguinal hernia and had both prostheses implanted randomly, one on each side. Early postoperative and chronic pain was evaluated using the visual analogue scale. Also recurrence rate and subjective evaluation of patients were analysed. RESULTS: Pain in the early postoperative period was inferior on the side where the self-adhesive mesh had been implanted (6.12 vs. 6.62, p=0.005 during the 1st postoperative day; 2.12 vs. 2.62, p=0.001 during the 7th postoperative day). Differences disappeared with the long-term evaluation (0.71 vs. 0.98, p=0.148 1 year after the surgery). The operative time was significantly shorter on the PPG mesh side (24.37 ± 5.1 in case of the PPG mesh and 29.66 ± 5.6 in case of the PLP mesh, p<0,001). Recurrence occurred in seven patients (7.8%), six of them (6.7%, CI 3.0-14.4) on the PPG mesh side and one (1.1%, CI 0.2-7.8) on the PLP side. These differences were not statistically significant (p=0.125) CONCLUSIONS: Although hernioplasty with self-adhesive mesh reduced early postoperative pain, this reduction was clinically irrelevant and it had no influence on chronic pain. There was a trend towards a higher recurrence rate when self-adhesive meshes were used, and although in this study differences were not statistically significant they should be confirmed in later studies using larger samples. Surgical procedures that do not need fixing sutures are promising, but further studies are needed before they become the gold standard of inguinal hernia repair.

A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis.

INTRODUCTION: CD226 genetic variants have been associated with a number of autoimmune diseases and recently with systemic sclerosis (SSc). The aim of this study was to test the influence of CD226 loci in SSc susceptibility, clinical phenotypes and autoantibody status in a large multicenter European population. METHODS: A total of seven European populations of Caucasian ancestry were included, comprising 2,131 patients with SSc and 3,966 healthy controls. Three CD226 single nucleotide polymorphisms (SNPs), rs763361, rs3479968 and rs727088, were genotyped using Taqman 5'allelic discrimination assays. RESULTS: Pooled analyses showed no evidence of association of the three SNPs, neither with the global disease nor with the analyzed subphenotypes. However, haplotype block analysis revealed a significant association for the TCG haplotype (SNP order: rs763361, rs34794968, rs727088) with lung fibrosis positive patients (PBonf = 3.18E-02 OR 1.27 (1.05 to 1.54)). CONCLUSION: Our data suggest that the tested genetic variants do not individually influence SSc susceptibility but a CD226 three-variant haplotype is related with genetic predisposition to SSc-related pulmonary fibrosis.

Influence of exercise on mood in postmenopausal women.

AIM AND OBJECTIVE: To evaluate the influence of an exercise programme on postmenopausal women with symptoms of anxiety and depression. BACKGROUND: The menopause is a period of hormonal changes when mood variations are probably more severe than at any other period of women's lives. DESIGN: Prospective study with control group and pre- and post-treatment measures, after six months treatment. Conducted at two healthcare clinics, in the province of Granada (Spain). METHODS: A convenience sample of 60 postmenopausal women aged 60-70 years, with symptoms of depression and anxiety, was recruited. The women were randomly divided into two groups: (1) control group, no treatment (n = 30); (2) exercise group, which carried out a programme of mixed physical exercises with musical support (n = 30). All subjects answered questionnaires for the Hamilton Anxiety Scale and the Brink and Yesavage Geriatric Depression Scale before and after treatment. RESULTS: In the exercise group, statistically significant improvements were observed in subjects with moderate and severe depression (18 and 22%, respectively) and in those with symptoms of anxiety. No such changes were observed in the control group. CONCLUSIONS: A controlled programme of physical exercise for postmenopausal women alleviates symptoms of anxiety and depression, and its inclusion in primary healthcare programmes should be considered. RELEVANCE TO CLINICAL PRACTICE: Menopausal women may benefit from physical exercise, which attenuates the effects of the physiological and psychological changes associated with the menopause and prevents pathologic changes.