STEP-CD study: ustekinumab use in paediatric Crohn's disease-a multicentre retrospective study from paediatric IBD Porto group of ESPGHAN.

Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7-17.2) with a median follow-up of 7.4 months (IQR 5.6-11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25-57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause.  Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12.

Prevalence of germline mutations in the TP53 gene in patients with early-onset breast cancer in the Mexican population.

BACKGROUND: Heterozygous germline TP53 gene mutations result in Li-Fraumeni Syndrome (LFS). Breast cancer (BC) is the most frequent tumor in young women with LFS. An important issue related to BC in the Mexican population is the average age at diagnosis, which is approximately 11 years younger than that of patients in the United States (U.S.) and Europe. The aim of this study was to determine the prevalence of germline mutations in TP53 among young Mexican BC patients. METHODS: We searched for germline mutations in the TP53 gene using targeted next-generation sequencing (NGS) in 78 BC patients younger than 45 years old (yo) who tested negative for BRCA1/2 mutations. A group of 509 Mexican women aged 45yo or older without personal or family BC history (parents/grandparents) was used as a control. RESULTS: We identified five patients with pathogenic variants in the TP53 gene, equivalent to 6.4% (5/78). Among patients diagnosed at age 36 or younger, 9.4% (5/55) had pathogenic TP53 mutations. Three of these variants were missense mutations (c.844C > T, c.517G > A, and c.604C > T), and the other two mutations were frameshifts (c.291delC and c.273dupC) and had not been reported previously. We also identified a variant of uncertain clinical significance (VUS), c.672G > A, which causes a putative splice donor site mutation. All patients with TP53 mutations had high-grade and HER2-positive tumors. None of the 509 patients in the healthy control group had mutations in TP53. CONCLUSIONS: Among Mexican BC patients diagnosed at a young age, we identified a high proportion with germline mutations in the TP53 gene. All patients with the TP53 mutations had a family history suggestive of LFS. To establish the clinical significance of the VUS found, additional studies are needed. Pathogenic variants of TP53 may explain a substantial fraction of BC in young women in the Mexican population. Importantly, none of these mutations or other pathological variants in TP53 were found in the healthy control group.

Acute Liver Failure: Outcome and Value of Pediatric End-Stage Liver Disease Score in Pediatric Cases.

PURPOSE: The aims of this study were to analyze the characteristics of patients with acute liver failure (ALF) in our center and evaluate the prognostic value of the Pediatric End-Stage Liver Disease (PELD) score calculated at admission. METHODS: A retrospective analysis of patients with ALF younger than 15 years between 2005 and 2013 was performed. Information collected included age, sex, etiology of ALF, laboratory tests, PELD score, stage of encephalopathy, and need for liver support devices such as MARS and/or liver transplant (LT) and survival. A poor prognosis was defined as the need for LT or death. RESULTS: Twenty patients (10 male patients, 50%) with a median age of 2.6 years (3 days-14.5 y old) were included. Acute liver failure was of indeterminate cause in 5 cases (25%). Within the recognized causes, the most frequent were viral hepatitis (herpes simplex virus, adenovirus, influenza B, Epstein-Barr virus), autoimmune hepatitis, and metabolopathies. Sixty percent presented with encephalopathy at diagnosis. Four patients were aided by a MARS liver support device. Six patients received a total of 7 transplants, all from deceased donors. The rate of spontaneous recovery was 45%. Currently 13 patients (65%) are living, 4 of them with an LT. Six patients died because of ALF. The mean PELD score of patients with spontaneous recovery was 15.31 (5.3-27.6) compared with a mean of 29.5 (17.2-39.4) in LT patients and 31.55 (15.8-52.4) for nonsurvivors (P = 0.013). CONCLUSIONS: High PELD scores at diagnosis were accurate predictors of a poor prognosis in our patients with ALF. This model may help in the clinical management of this entity, although prospective validation is needed.

The Use of Bone Morphogenetic Protein in Spinal Transforaminal Lumbar Interbody Fusion: Our Experience.

OBJECTIVE: Since its introduction and FDA approval, rhBMP-2 has been adopted by spine surgeons as a substitute for ICBG in numerous spinal fusion techniques. As broad clinical use increased, reports on potential complications associated with rhBMP-2 also increased. We provide our experience with TLIF using rhBMP-2 or ICBG in an entirely Hispanic population. METHODS: This was a 2-year retrospective study of 67 patients, with 26 in the rhBMP-2 group and 41 in the ICBG group, who underwent TLIF. Pertinent information was obtained through review of the medical records documenting complications, intraoperative times, and EBL, among other things. RESULTS: There were 28 post-operative complications with 15 (53.6%) in the ICBG group and 13 (46.4%) in the rhBMP-2 group. The average EBL was 572.3 mL (SD: 411.8) in the ICBG group and 397.9 mL (SD: 312.2) in the rhBMP-2 group. The average intraoperative time was 243.1 minutes (SD: 79.5) in the ICBG group and 226.5 minutes (SD: 64.7) in the rhBMP-2 group. Fifty-two patients underwent open TLIF and 15 patients underwent MI TLIF. The average EBL was 571.2 mL (SD: 375.3) in the open TLIF group and 228.3 mL (SD: 299.3) in the MI-TLIF group. The average intraoperative time was 241.0 minutes (SD: 76.0) for patients in the open TLIF group and 218.8 minutes (SD: 65.0) for those in the MI-TLIF group. There were no new cancer events at any of the 2-year follow-up visits. RESULTS: Our results suggest that the safety profile of rhBMP-2 may be inferior to that of ICBG, rejecting the possibility of ICBG being replaced by rhBMP-2 as the gold standard for spinal fusion.

Correction of joint angles from Kinect for balance exercising and assessment.

The new generation of videogame interfaces such as Microsoft's Kinect opens the possibility of implementing exercise programs for physical training, and of evaluating and reducing the risks of elderly people falling. However, applications such as these might require measurements of joint kinematics that are more robust and accurate than the standard output given by the available middleware. This article presents a method based on particle filters for calculating joint angles from the positions of the anatomical points detected by PrimeSense's NITE software. The application of this method to the measurement of lower limb kinematics reduced the error by one order of magnitude, to less than 10°, except for hip axial rotation, and it was advantageous over inverse kinematic analysis, in ensuring a robust and smooth solution without singularities, when the limbs are out-stretched and anatomical landmarks are aligned.

Assessing the In Vitro Individual and Combined Effect of Arthrobotrys oligospora and A. musiformis (Orbiliales) Liquid Culture Filtrates against Infective Larvae of the Sheep Blood-Feeding Nematode Haemonchus contortus (Trichostrongylidae).

BACKGROUND: Arthrobotrys species are nematophagous fungi that secrete extracellular nematocidal products (ECP). The individual and combined effects of ECP from Arthrobotrys oligospora (Ao) and A. musiformis (Am) growth in liquid media against Haemonchus contortus L3 (HcL3) were assessed. METHODS: The isolation, morphological (MI) and molecular identification (Mol-I), assessment of nematocidal activity (NA) of fungal liquid culture filtrates (LCF) in two liquid media alone and in combination and the myco-compound profile identification (MCP) were performed. RESULTS: The MI suggested that the fungi corresponded to the species Ao and Am. This result was confirmed by PCR analysis followed by sequencing, alignment and a phylogenetic analysis. Likewise, the highest Hc mortalities were 91.4% with individual LCF of Am and 86.2% with those of Ao at the highest concentration (100 mg/mL) in Czapek-Dox Broth. The combination of both LCF resulted in a similarly high larval mortality with no statistical differences in relation to individual activity (p > 0.05). The MCP showed the presence of alkaloids in both fungi. Coumarins, sterols and saponins were found only in Ao. MAIN CONCLUSIONS: Both fungi produced ECP with a high NA that could be identified and assessed in future studies as potential natural anthelmintic compounds.

Postnatal Surgical Correction of Myelomeningoceles: Preoperative and Intraoperative Risk Factors Associated with Postoperative Neurologic Outcomes.

OBJECTIVE: Open spina bifida or myelomeningocele (MMC) is a congenital defect that results from failure of caudal neurulation. We present a case series of patients who were treated with postnatal surgical correction for MMC, evaluating the possible preoperative and intraoperative risk factors associated with neurologic outcomes. METHODS: A retrospective chart review of patients who underwent postnatal surgical correction for MMCs over 11 years at our institution was performed. MMCs were classified based on their morphologic configuration into 3 types. Type I includes defects without a sac and there is cerebrospinal fluid (CSF) leak. Type II includes where there is a sac ≤4 cm, with or without CSF leak. Type III includes defects with a sac that are greater than 4 cm. RESULTS: Fifty patients were included. The median age of gestation at surgery was 37.4 weeks. There were 30 females (60%). All mothers received adequate folate supplementation. All patients underwent surgical correction in the first 48 hours. Lower extremity motor function at the last clinical follow-up was normal in 34 patients (68%). CSF leak, infection, and mortality were 8%, 2%, and 0%, respectively. Twenty-one patients (42%) underwent ventriculoperitoneal shunt for hydrocephalus. CONCLUSIONS: Despite there being no statistically significant associations with a timely closure, all cases were treated within the first 48 hours and this could influence the low complication rate. Individuals of Hispanic background who received appropriate folate supplementation still had high rates of MMC and we posit that this may be caused in part by a genetic/molecular predisposition.

Efficacy of an Opioid-Sparing Perioperative Multimodal Analgesia Protocol on Posterior Lumbar Fusion in a Hispanic Population: A Randomized Controlled Trial.

INTRODUCTION: Posterior lumbar fusion surgery has become more common amid an aging population, with degenerative disease as its most common indication. Historically, postoperative pain control for spine surgery has relied on opioids. However, opioid use is associated with adverse effects such as dependence, respiratory depression, and altered cognition. Our study aimed to determine whether an opioid-sparing multimodal analgesia regimen (ketorolac, orphenadrine, and gabapentin) could be a viable alternative to diminish opioid use compared with a standard opioid-based regimen in Hispanic patients undergoing posterior lumbar spinal fusion. METHODS: This was a randomized controlled trial of Hispanic patients scheduled to undergo elective posterior spinal fusion. Inclusion criteria included age 30 to 85 years, Hispanic ethnicity, lumbar stenosis between L1 and S1, elective posterior spinal fusion with instrumentation, American Society of Anesthesiologists Score <2, and consent to participate in the study. Patients were randomized into two groups, an experimental multimodal analgesia and control (opioid-based) treatment groups, and outcomes such as morphine milligram equivalents used, visual analog scale score, and length of hospital stay were compared between the groups. RESULTS: The MMA experimental group used significantly lower amounts of opioid (measured with morphine milligram equivalent) than the opioid-based group during the 12-hour and 24-hour postoperative periods ( P -value = 0.023 and P -value = 0.033, respectively). No statistically significant difference was observed in opioid use in the 48-hour postoperative period between both groups ( P -value = 0.066). The MMA group had significantly lower VAS scores reported at the 12-hour, 24-hour, and 48-hour postoperative periods compared with the opioid-based group ( P -values = 0.016, 0.020, and 0.020, respectively). No difference was observed in the length of hospital stay between groups ( P -value = 0.169). DISCUSSION: Implementing an MMA protocol in Hispanic patients undergoing posterior lumbar fusion resulted in decreased overall opioid use and decreased pain intensity compared with the opioid-based group. MMA is an effective alternative for pain control in patients who want to avoid opioid use. CLINICAL TRIAL REGISTRATION: Identifier: NCT05413902.

Methylation-acetylation interplay activates p53 in response to DNA damage.

p53, an important tumor suppressor protein, exerts its function mostly as a sequence-specific transcription factor and is subjected to multiple posttranslational modifications in response to genotoxic stress. Recently, we discovered that lysine methylation of p53 at K372 by Set7/9 (also known as SET7 and Set9) is important for transcriptional activation and stabilization of p53. In this report we provide a molecular mechanism for the effect of p53 methylation on transcription. We demonstrate that Set7/9 activity toward p53, but not the nucleosomal histones, is modulated by DNA damage. Significantly, we show that lysine methylation of p53 is important for its subsequent acetylation, resulting in stabilization of the p53 protein. These p53 modification events can be observed on the promoter of p21 gene, a known transcriptional target of p53. Finally, we show that methylation-acetylation interplay in p53 augments acetylation of histone H4 in the promoter of p21 gene, resulting in its subsequent transcriptional activation and, hence, cell cycle arrest. Collectively, these results suggest that the cross talk between lysine methylation and acetylation is critical for p53 activation in response to DNA damage and that Set7/9 may play an important role in tumor suppression.

Cananea copper mine: An international effort to improve hazardous working conditions in Mexico.

A team of international occupational health and safety professionals evaluated the working conditions and health status of miners at a giant open-pit copper mine in Cananea, Mexico. Workers in the ore processing plants were exposed to levels of crystalline silica 10 times the Mexican regulatory limit, high levels of acid mist and noise, and numerous safety hazards, including unguarded machinery and malfunctioning 10- and 15-ton cranes. Lung function testing and interviews with physicians showed a substantial percentage of miners with adverse respiratory symptoms including shortness of breath (46%), wheezing (12%), coughing (12%), and elevated sputum production (10%). The mine owner, Grupo Mexico, violated Mexican law by failing to conduct an industrial hygiene survey sufficient to identify, evaluate, and control health hazards including exposure to mineral dust (including silica), acid mists, airborne solvents, high noise levels, high vibration levels, and extreme temperatures.

[Gastric polyposis due to treatment with proton pump inhibitors]. / Poliposis gástrica secundaria a tratamiento con inhibidores de la bomba de protones.

Fundic gland polyps can appear sporadically or in association with familial adenomatous polyposis syndrome. An association between fundic gland polyps and prolonged treatment with proton pump inhibitors has been described, as has their regression after withdrawal of these inhibitors. Dysplastic components are not usually associated. We describe four patients who were receiving chronic treatment with proton pump inhibitors. The results of prior endoscopic analysis were normal. The presence of multiple fundic gland polyps was detected as was their disappearance 6 months after treatment cessation.

Lethal hepatopathy and leukodystrophy caused by a novel mutation in MPV17 gene: description of an alternative MPV17 spliced form.

It has recently been reported that mutations in MPV17 gene may be causative of mtDNA depletion syndrome (MDS). Patients with this alteration presented with severe liver failure, hypoglycemia, growth retardation and neurological symptoms during the first year of life. We report on the clinical, biochemical and molecular findings of a patient presenting with lethal hepatopathy, polyneuropathy, neurological regression and leukodystrophy associated with mutations in MPV17. Mitochondrial respiratory chain activities were low in liver and within reference values in muscle. However, levels of mtDNA were markedly reduced both in muscle and liver. A novel homozygous mutation in MPV17, c.70+5G>A (IVS1+5G>A), was identified. This intronic change causes the full-length cDNA loss, probably due to loss of strength of the splice donor site of exon 1. Western blot analysis, performed in liver homogenates, further corroborates these results as the amount of patient's protein was highly reduced, or almost absent, compared with that of controls. We also identified an additional alternative spliced form in controls and in the patient, due to exon 2 skipping, that has not previously been reported.

Low adherence to colonoscopy in the screening of first-degree relatives of patients with colorectal cancer.

BACKGROUND: Colonoscopy is one of the methods of choice for screening relatives of patients with colorectal cancer. OBJECTIVE: To evaluate the rate of adherence to colonoscopy in first-degree relatives of patients with colorectal cancer and describe the lesions found. METHODS: A prospective, cross-sectional, multicentre, nationwide study was conducted. The study population was composed of first-degree relatives of patients with colorectal cancer selected randomly from the EPICOLON study. Seventy-four index patients were included. These had 342 living first-degree relatives (parents, siblings and children), of whom 281 were interviewed. RESULTS: The adherence rate was 38% (107/281). Adherence was greater in families with a higher degree of familial aggregation for colorectal cancer (88.9% for Amsterdam vs 33.3% for Bethesda and sporadic cancer; p<0.05), an index patient aged under 65 years (60% for patients <65 years vs 32.9% for patients >or=65 years; p<0.05) and an index patient who was female (46.2% for women vs 31% for men; p = 0.28). Adherence was also greater in relatives under 65 years (54% in patients <65 years vs 18% in patients >or=65 years; p = 0.05), in female relatives (49% in female relatives vs 27.3% in male relatives; p<0.05) and in siblings and children (40% in siblings and children vs 13% in parents; p<0.05). Lesions were found in 26% (28/107) of the study population. Nine (8.4%) individuals had a total of 18 advanced lesions. CONCLUSIONS: These results indicate that adherence to colonoscopy in our population of first-degree relatives was low. The adherence was more frequently associated with a higher degree of familial aggregation, a relative age of under 65 years, a sibling or offspring relationship, and female sex.

Effect of fatigue and gender on kinematics and ground reaction forces variables in recreational runners.

The presence of fatigue has been shown to modify running biomechanics. Overall in terms of gender, women are at lower risk than men for sustaining running-related injuries, although it depends on the factors taken into account. One possible reason for these differences in the injury rate and location might be the dissimilar running patterns between men and women. The purpose of this study was to determine the effect of fatigue and gender on the kinematic and ground reaction forces (GRF) parameters in recreational runners. Fifty-seven participants (28 males and 29 females) had kinematic and GRF variables measured while running at speed of 3.3 m s-1 before and after a fatigue test protocol. The fatigue protocol included (1) a running Course-Navette test, (2) running up and down a flight of stairs for 5 min, and (3) performance of alternating jumps on a step (five sets of 1 minute each with 30 resting seconds between the sets). Fatigue decreased dorsiflexion (14.24 ± 4.98° in pre-fatigue and 12.65 ± 6.21° in fatigue condition, p < 0.05) at foot strike phase in females, and plantar flexion (-19.23 ± 4.12° in pre-fatigue and -18.26 ± 5.31° in fatigue condition, p < 0.05) at toe-off phase in males. These changes led to a decreased loading rate (88.14 ± 25.82 BW/s in pre-fatigue and 83.97 ± 18.83 BW/s in fatigue condition, p < 0.05) and the impact peak in females (1.95 ± 0.31 BW in pre-fatigue and 1.90 ± 0.31 BW in fatigue condition, p < 0.05), and higher peak propulsive forces in males (-0.26 ± 0.04 BW in pre-fatigue and -0.27 ± 0.05 BW in fatigue condition, p < 0.05) in the fatigue condition. It seems that better responses to impact under a fatigue condition are observed among women. Further studies should confirm whether these changes represent a strategy to optimize shock attenuation, prevent running injuries and improve running economy.

Cyclooxygenase 2 expression in colorectal cancer with DNA mismatch repair deficiency.

BACKGROUND: Cyclooxygenase 2 (COX-2) overexpression is a frequent but not universal event in colorectal cancer. It has been suggested that COX-2 protein expression is reduced in colorectal cancer with a defective mismatch repair (MMR) system, a phenomenon commonly associated with hereditary nonpolyposis colorectal cancer (HNPCC) but also present in up to 15% of sporadic tumors. AIM: To assess COX-2 expression in a large series of fully characterized colorectal cancer patients with respect to the MMR system and to dissect the mechanisms responsible for altered COX-2 expression in this setting. PATIENTS AND METHODS: MMR-deficient colorectal cancer were identified in a nationwide, prospective, multicenter study (EPICOLON project). Control MMR-proficient colorectal cancer patients were randomly selected. COX-2 expression was evaluated by immunohistochemistry. Personal and familial characteristics, as well as MSH2/MLH1 expression and germ line mutations, were evaluated. RESULTS: One hundred fifty-three patients, 46 with MMR deficiency and 107 with MMR proficiency, were included in the analysis. Overall, tumor COX-2 overexpression was observed in 107 patients (70%). COX-2 overexpression was observed in 85 patients (79%) with a MMR-proficient system, but only in 22 patients (48%) with a MMR-deficient colorectal cancer (P < 0.001). The lack of COX-2 overexpression was independently associated with a MMR-deficient system (odds ratio, 3.89; 95% confidence interval, 1.78-8.51; P = 0.001) and a poor degree of differentiation (OR, 3.83; 95% CI, 1.30-11.31; P = 0.015). In the subset of patients with a MMR-deficient colorectal cancer, lack of COX-2 overexpression correlated with a poor degree of differentiation, no fulfillment of Amsterdam II criteria, absence of MSH2/MLH1 germ line mutations, presence of tumor MSH2 expression, and lack of tumor MLH1 expression. CpG island promoter hypermethylation of COX2 was observed in 6 of 18 (33%) tumors lacking COX-2 expression in comparison with 2 of 28 (7%) tumors expressing this protein (P = 0.04). CONCLUSIONS: Up to half of MMR-deficient colorectal cancer do not show COX-2 overexpression, a fact observed almost exclusively in patients with sporadic forms. COX2 hypermethylation seems to be responsible for gene silencing in one third of them. These results suggest the potential utility of nonsteroidal anti-inflammatory drugs in HNPCC chemoprevention and may explain the lack of response of this approach in some sporadic tumors.

Infección por el Virus del Mono: Primer caso reportado en Paraguay

Desde hace varios años es conocida la infección transmitida por el virus de la viruela símica, caracterizada por afecciones que transitan desde leves lesiones cutáneas hasta afecciones más complejas; sin embargo, desde el mes de mayo, ha habido un rebrote de casos con notificación de alerta epidemiológica a nivel mundial, declarándose luego una emergencia de salud pública por la OMS en el mes de julio. La mayoría de los casos fueron observados en hombres que tienen sexo con hombres lo que sugiere la mayor exposición las relaciones sexuales y eventualmente ha propuesto la interrogante de nuevas mutaciones genéticas. Se presenta el primer caso de Viruela del Mono en Paraguay, en paciente adulto joven, masculino, de compromiso leve, sin repercusión sistémica, y con evolución favorable. Las medidas sanitarias son nuevamente el pilar fundamental para la toma de directrices y manejos protocolizados a fin de alcanzar una correcta vigilancia en salud pública.

The infection transmitted by the monkeypox virus has been known for a few years, characterized by conditions from mild skin lesions to another more complex; however, since the month of May, there has been a resurgence of cases with notification of epidemiological alert worldwide, later declaring a public health emergency by the WHO in July. Most of the cases were observed in men who have sex with men, suggesting the greatest exposure to sexual intercourse and eventually raising the question of new genetic mutations. The first case of Monkeypox in Paraguay is presented, in a young adult male patient, with mild involvement, without systemic repercussions, and with a favorable evolution. Sanitary measures are once again the fundamental pillar for the adoption of protocolized guidelines and procedures in order to achieve proper public health surveillance.

Resección Tubular Microquirúrgica de un Subependimoma Extenso del Ventrículo Lateral Izquierdo: Video Operatorio en 2D / Microsurgical Tubular Resection of an Extensive Subependymoma of the Left Lateral Ventricle: Operative Video in 2D

Introducción: Los subependimomas intracraneales son raros, representan el 0.2-0.7% de todos los tumores del sistema nervioso central1,2 y se originan en los ventrículos laterales en el 30-40% de los casos.3 Los síntomas usualmente se asocian a hipertensión endocraneana secundaria a hidrocefalia obstructiva.4 La resección completa del tumor es curativa en esta patología.5 El abordaje trans-surcal es seguro para lesiones ventriculares profundas y el uso de los retractores tubulares minimizan la retracción del parénquima cerebral evitando la compresión directa con valvas. Esto permite disminuir la presión del tejido cerebral que puede ocluir los vasos y producir isquemia local generando una lesión neurológica permanente. Descripción del caso: Se presenta el caso de una paciente de 66 años, diestra, con cefalea crónica que aumenta en frecuencia en el último mes. La resonancia cerebral contrastada muestra un tumor extenso en el ventrículo lateral izquierdo con signos de hidrocefalia obstructiva. Intervención: Se coloca la paciente en posición supina. Se hace una incisión bicoronal y se hace un abordaje trans-surcal F1/F2 izquierdo. Se coloca un retractor tubular guiado con el puntero de neuronavegación, introduciéndolo directamente en el parénquima cerebral y fijándolo al soporte de Leyla. Se colocó un catéter de ventriculostomía contralateral y se retira a las 48 horas sin complicaciones asociadas. La resonancia contrastada postoperatoria demuestra una resección completa del tumor. El análisis de patología reveló un subependimoma grado I de la clasificación de la Organización Mundial de la Salud. La paciente presentó transitoriamente apatía y pérdida del control del esfínter urinario que resolvieron completamente a las 3 semanas después de la cirugía. Se firmó un consentimiento firmado para la publicación de la información utilizada en este trabajo. Conclusión: La resección completa microscópica de un subependimoma extenso del ventrículo lateral izquierdo es factible a través de un abordaje tubular transulcal.

Introduction: Intracranial subependymomas are rare, representing only 0.2-0.7% of all central nervous system tumors1,2 and arise in the lateral ventricles in 30-40% of the cases.3 Symptoms depend on tumor location and usually arise when the cerebrospinal fluid (CSF) is blocked, generating a consequent intracranial hypertension.4 Microsurgical gross-total resection is possible and curative for these tumors.5 The transcortical/trans-sulcal approach is a safe approach for the access of deep-seated intraventricular lesions. The use of tubular retractor systems minimizes retraction injury when passing through the cortex and deep white matter tracts. This allows a decrease in the pressure on brain tissue that can occlude the brain vessels and produce local ischemia and a consequent permanent neurological injury. Case description: This is a case of a 66-year-old woman who presented chronic headaches that increased in frequency in the last month. Enhanced-brain MRI demonstrated a large left ventricular lesion with signs of obstructive hydrocephalus. Procedure: Patient was positioned supine. A bicoronal incision was used to perform a left frontal craniotomy. An F1/F2 transcortical/trans-sulcal approach was used. A guided tubular retractor is placed with the neuronavigation pointer, inserting it directly into the brain parenchyma and fixing it to the Leyla support. Postoperative postcontrast MRI demonstrated a complete resection of the tumor. Histopathological analysis revealed a subependymoma (World Health Organization Grade I). The patient presented transient apathy and loss of urinary sphincter control that completely resolved 3 weeks after surgery. Written informed consent was obtained for publication of information used for this work. Conclusions: A complete microsurgical resection of a large left ventricular subependymoma is feasible through a trans-sulcal tubular approach.

PUMA project: Active involving of end users to achieve a smart solution to prevent pressure ulcer.

This paper shows the benefits to include spinal cord injury users and the other stakeholders during the development of a new system to prevent pressure ulcers. The complementary of information has been key and has enhanced the possibility to achieve market acceptance and introduction.

Two-week, high-dose proton pump inhibitor, moxifloxacin triple Helicobacter pylori therapy after failure of standard triple or non-bismuth quadruple treatments.

BACKGROUND: Aim was to evaluate the efficacy and tolerability of a moxifloxacin-containing second-line triple regimen in patients whose previous Helicobacter pylori eradication treatment failed. METHODS: Prospective multicentre study including patients in whom a triple therapy or a non-bismuth-quadruple-therapy failed. Moxifloxacin (400mg qd), amoxicillin (1g bid), and esomeprazole (40 mg bid) were prescribed for 14 days. Eradication was confirmed by (13)C-urea-breath-test. Compliance was determined through questioning and recovery of empty medication envelopes. RESULTS: 250 patients were consecutively included (mean age 48 ± 15 years, 11% with ulcer). Previous (failed) therapy included: standard triple (n = 179), sequential (n = 27), and concomitant (n = 44); 97% of patients took all medications, 4 were lost to follow-up. Intention-to-treat and per-protocol eradication rates were 82.4% (95% CI, 77-87%) and 85.7% (95% CI, 81-90%). Cure rates were similar independently of diagnosis (ulcer, 77%; dyspepsia, 82%) and previous treatment (standard triple, 83%; sequential, 89%; concomitant, 77%). At multivariate analysis, only age was associated with eradication (OR = 0.957; 95% CI, 0.933-0.981). Adverse events were reported in 25.2% of patients: diarrhoea (9.6%), abdominal pain (9.6%), and nausea (9.2%). CONCLUSION: 14-day moxifloxacin-containing triple therapy is an effective and safe second-line strategy in patients whose previous standard triple therapy or non-bismuth quadruple (sequential or concomitant) therapy has failed, providing a simple alternative to bismuth quadruple regimen.

Designing pediatric vaccine formularies and pricing pediatric combination vaccines using operations research models and algorithms.

The National Immunization Program, housed within the Centers for Disease Control and Prevention in the USA, has identified several challenges that must be faced in childhood immunization programs to deliver and procure vaccines that immunize children from the plethora of childhood diseases. The biomedical issues cited include how drug manufacturers can combine and formulate vaccines, how such vaccines are scheduled and administered and how economically sound vaccine procurement can be achieved. This review discusses how operations research models can be used to address the economics of pediatric vaccine formulary design and pricing, as well as how such models can be used to address a new set of pediatric formulary problems that will surface with the introduction of pediatric combination vaccines into the US pediatric immunization market.