Long-term follow-up of the ketogenic diet for refractory epilepsy: Multicenter Argentinean experience in 216 pediatric patients

Purpose

In this Argentinean retrospective, collaborative, multicenter study, we examine the efficacy and tolerability of the ketogenic diet (KD) for different epilepsy syndromes.

Materials and methods

we evaluated the clinical records of 216 patients started on the KD between March 1, 1990 and December 31, 2010.

Results

One hundred forty of the initial patients (65%) remained on the diet at the end of the study period. Twenty-nine patients (20.5%) became seizure free and 50 children (36%) had a 75–99% decrease in seizures. Thus, 56.5% of the patients had a seizure control of more than 75%. The best results were found in patients with epilepsy with myoclonic-astatic seizures, Lennox–Gastaut syndrome, and West syndrome. Good results were also found in patients with Dravet syndrome, in those with symptomatic focal epilepsy secondary to malformations of cortical development, and in patients with tuberous sclerosis. Seizures were significantly reduced in four patients with fever-induced refractory epileptic encephalopathy in school-age children and in two patients with epileptic encephalopathy with continuous spikes and waves during slow sleep. The median period of follow-up after discontinuation of the diet was 6 years. Twenty patients who had become seizure free discontinued the diet, but seizures recurred in five (25%). Of 40 patients with a seizure reduction of more than 50% who discontinued the diet, 10 presented with recurrent seizures.

Conclusion

The ketogenic diet is a good option in the treatment of refractory epilepsy. After discontinuing the diet, seizures recurrence occurred in few patients.     

Treatment of refractory adult‐onset pityriasis rubra pilaris with TNF‐alpha antagonists: a case series

Background Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis with frequent clinical presentation as erythroderma. Conventional systemic treatment is often unsatisfactory and limited by long‐term toxicity. The use of tumour necrosis factor (TNF) antagonists has been reported previously in single cases, but lacking long‐term follow‐up or comparison between different biological agents. Objectives To assess the long‐term efficacy and safety of TNF‐alpha antagonist, infliximab and etanercept, either in monotherapy or in combination therapy of severe, refractory adult‐onset PRP. Methods Seven patients of adult‐onset PRP, six newly diagnosed type‐I and 1 type‐II, which were resistant or ineligible to conventional systemic treatment, received a single course of infliximab or etanercept therapy, alone or in combination with low‐dose acitretin (>0.25 mg/kg/daily). After complete remission and treatment discontinuation, a follow‐up period of 12 months was evaluated for relapses. Results Six patients obtained complete remission after a single course of anti‐TNF‐alpha therapy: mean therapy duration was 19.3 weeks (range 6–48 weeks). All patients obtained significant clearing (>75% of body surface area) of skin lesions at week 12. Two patients with marked keratoderma developed localized disease recurrence during treatment. During follow‐up, only a single patient, affected by type II PRP, had disease relapse. Conclusions Both TNF‐alpha antagonists proved successful for the treatment of refractory, adult‐onset PRP, yielding complete and persistent clinical responses in type‐I PRP. Infliximab was associated with a more rapid onset of action, while treatment duration was comparable with etanercept. PRP type II warranted long‐term therapy and showed relapse after drug discontinuation.     

Ectopic ureter and ureterocele: their varied sonographic manifestations

The sonographic examinations of four patients with simple ectopic ureters and 11 with ectopic ureteroceles were reviewed to determine distinguishing characteristics. Ectopic ureters, in cases of extreme dilatation and tortuosity, sometimes mimic multiseptated, cystic abdominal masses. However, the proximal portions of some severely dilated ureters are surprisingly small. Ectopic ureters sometimes indent the lower vesical wall, simulating a ureterocele. Ectopic ureteroceles are dynamic structures, changing in shape and size according to intravesical pressure. The lower pole of a duplex kidney may be difficult to detect because of displacement by the dilated upper renal pelvis and ureter. The renal parenchyma associated with an ectopic ureter may be equally difficult or impossible to find because of diminutive dysplasia or, less commonly, acquired atrophy. Dysplasia is characterized sonographically by highly echogenic parenchyma, lack of corticomedullary differentiation, and occasionally massive enlargement by cysts. Ectopic ureters and ureteroceles can be identified by fetal sonography.     

Enhancement of chemotactic factor-stimulated neutrophil oxidative metabolism by leukotriene B4

Leukotriene B4 (LTB4) is a potent primary stimulator of neutrophil chemotaxis, aggregation, and degranulation and induces superoxide production at higher concentrations. In order to determine whether LTB4 modulates neutrophil responses to oxidative stimuli, human neutrophils (PMNs) were incubated with LTB4 prior to stimulation with f-Met-Leu-Phe (fMLP, 10(-7) mol/L), opsonized zymosan (OZ, 250 micrograms/mL), or phorbol myristate acetate (PMA, 32 nmol/L). Superoxide (O2-) production by stimulated PMNs was assessed by the superoxide dismutase-inhibitable reduction of cytochrome c. LTB4 alone did not stimulate O2- production in concentrations below 10(-7) mol/L and had no effect on the O2- assay. In the concentration range of 10(-12) to 10(-8) mol/L, LTB4 did not alter O2- release induced by OZ or PMA. In contrast, LTB4-treated cells demonstrated enhanced O2- production following exposure to fMLP, and in the presence of 10 nmol/LLTB4, generated 180% +/- 41% of O-2 quantities produced by control cells (n = 23). Enhancement was LTB4 dose-dependent, was maximal in the range of 1 to 10 nmol/L LTB4, was not reversed by removal of the lipid from the medium prior to fMLP stimulation, and was not dependent on the presence of Ca++ or Mg++ in the suspending medium. Chemiluminescence of fMLP-stimulated neutrophils was increased to 323% of controls in neutrophils preincubated with 10 nmol/L LTB4. Unlike augmentation of oxidative responses to fMLP seen with other degranulating stimuli, enhancement by LTB4 was not correlated with an increase in 3H-fMLP receptor binding. These results indicate that, in addition to its primary effects on neutrophil function, LTB4 modulates PMN oxidative responses to the chemotactic peptide and, thus, may amplify the release of oxygen metabolites at inflammatory foci.     

Randomized clinical and manometric study of advancement flap versus fistulotomy with sphincter reconstruction in the management of complex fistula-in-ano

BACKGROUND: The goal of this study was to compare the outcomes of advancement flap (AF) versus fistulotomy with sphincter reconstruction (FSR) for primary complex fistula-in-ano in terms of recurrence and anal function. METHODS: A randomized clinical trial was conducted to compare AF with FSR. Preoperative and postoperative evaluation included physical examination, anal ultrasonography, and anal manometry, with a minimum follow-up period of 24 months. Anal continence was evaluated using the Wexner Continence Grading Scale (scale, 0-20). RESULTS: Sixty patients were randomized to AF (group 1, N = 30) or FSR (group 2, N = 30). Three patients from group 1 and 2 patients from group 2 were excluded from the study because of active sepsis at surgery. Fistulas were classified as high transsphincteric in 44 patients (80%) and suprasphincteric in 11 patients (20%). Demographic and clinical features showed no differences between the 2 groups. The mean Wexner Continence Grading Scale did not vary significantly after surgery in either group, and there was no difference between the groups. On anal manometry there was a significant decrease in the maximum resting pressure after surgery in both groups, and in the maximum squeeze pressure in the AF group, but neither the maximum resting pressure nor the maximum squeeze pressure differed significantly between groups, either before or after surgery. Two fistulas from each group recurred after surgery (7.4% and 7.1%, respectively). The mean follow-up period was 36 months (range, 24-52 mo). CONCLUSIONS: FSR compares with AF in terms of postoperative continence and recurrence. Anal continence and manometric values are not jeopardized in either technique.     

Use of a virtual immersion computer simulator as a model for basic training in laparoscopic urology

Backgroundto date, it has not been defined the best method for teaching urologic laparoscopy, however it is well recognized that it involves a steep learning curve.MethodsA course of Laparoscopic Urology was done in our Institute. The program included skill practices in a virtual immersion simulator which evaluated, the score and time to complete each activity. This was done in a group of residents with previous experience with this virtual simulator (group 1) and another group of residents with no experience (group 2). Four different basic tasks were performed in the virtual simulator, which included: coordination, cutting, clip application and performing a simple suture.ResultsWhen we compared the scores between both groups the mean scores for each task were superior in group 1 compared to the group 2, with no statistically significant difference, however when we compared the time to complete each task, it was shorter in group 1 compared to group 2 with a statistically significant difference.ConclusionsThe performance of residents without experience in a virtual simulator was similar to that of previously trained residents, however it takes less time to complete each task as the resident gains experience in these simulators. The use of virtual simulators for laparoscopy training are useful when learning basic techniques allowing the surgeon to improve hand dexterity and coordination in laparoscopic surgery.     

Rehabilitación multimodal en cirugía de urgencias: ¿utopía o realidad?

Enhanced Recovery After Surgery (ERAS) constitutes the application of a series of perioperative measures based on the evidence, in order to achieve a better recovery of the patient and a decrease of the complications and the mortality. These ERAS programs initially proved their advantages in the field of colorectal surgery being progressively adopted by other surgical areas within the general surgery and other surgical specialties. The main excluding factor for the application of such programs has been the urgent clinical presentation, which has caused that despite the large volume of existing literature on ERAS in elective surgery, there are few studies that have investigated the effectiveness of these programs in surgical patients in emergencies. The aim of this article is to show ERAS measures currently available according to the existing evidence for emergency surgery.     

Role of preoperative carbohydrate loading: a systematic review

INTRODUCTION

Surgical stress in the presence of fasting worsens the catabolic state, causes insulin resistance and may delay recovery. Carbohydrate rich drinks given preoperatively may ameliorate these deleterious effects. A systematic review was undertaken to analyse the effect of preoperative carbohydrate loading on insulin resistance, gastric emptying, gastric acidity, patient wellbeing, immunity and nutrition following surgery.

METHODS

All studies identified through PubMed until September 2011 were included. References were cross-checked to ensure capture of cited pertinent articles.

RESULTS

Overall, 17 randomised controlled trials with a total of 1,445 patients who met the inclusion criteria were identified. Preoperative carbohydrate drinks significantly improved insulin resistance and indices of patient comfort following surgery, especially hunger, thirst, malaise, anxiety and nausea. No definite conclusions could be made regarding preservation of muscle mass. Following ingestion of carbohydrate drinks, no adverse events such as apparent or proven aspiration during or after surgery were reported.

CONCLUSIONS

Administration of oral carbohydrate drinks before surgery is probably safe and may have a positive influence on a wide range of perioperative markers of clinical outcome. Further studies are required to determine its cost effectiveness.     

Sloths host Anhanga virus‐related phleboviruses across large distances in time and space

Sloths are genetically and physiologically divergent mammals. Phleboviruses are major arthropod‐borne viruses (arboviruses) causing disease in humans and other animals globally. Sloths host arboviruses, but virus detections are scarce. A phlebovirus termed Anhanga virus (ANHV) was isolated from a Brazilian Linnaeus's two‐toed sloth (Choloepus didactylus) in 1962. Here, we investigated the presence of phleboviruses in sera sampled in 2014 from 74 Hoffmann's two‐toed (Choloepus hoffmanni, n = 65) and three‐toed (Bradypus variegatus, n = 9) sloths in Costa Rica by broadly reactive RT‐PCR. A clinically healthy adult Hoffmann's two‐toed sloth was infected with a phlebovirus. Viral load in this animal was high at 8.5 × 10⁷ RNA copies/ml. The full coding sequence of the virus was determined by deep sequencing. Phylogenetic analyses and sequence distance comparisons revealed that the new sloth virus, likely representing a new phlebovirus species, provisionally named Penshurt virus (PEHV), was most closely related to ANHV, with amino acid identities of 93.1%, 84.6%, 94.7% and 89.0% in the translated L, M, N and NSs genes, respectively. Significantly more non‐synonymous mutations relative to ANHV occurred in the M gene encoding the viral glycoproteins and in the NSs gene encoding a putative interferon antagonist compared to L and N genes. This was compatible with viral adaptation to different sloth species and with micro‐evolutionary processes associated with immune evasion during the genealogy of sloth‐associated phleboviruses. However, gene‐wide mean dN/dS ratios were low at 0.02–0.15 and no sites showed significant evidence for positive selection, pointing to comparable selection pressures within sloth‐associated viruses and genetically related phleboviruses infecting hosts other than sloths. The detection of a new phlebovirus closely‐related to ANHV, in sloths from Costa Rica fifty years after and more than 3,000 km away from the isolation of ANHV confirmed the host associations of ANHV‐related phleboviruses with the two extant species of two‐toed sloths.