Retrospective cohort analysis of neoadjuvant treatment and survival in resectable and borderline resectable pancreatic ductal adenocarcinoma in a high volume referral centre.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease. Neoadjuvant therapy (NA) with chemotherapy (NAC) and radiotherapy (RT) prior to surgery provides promise. In the absence of prospective data, well annotated clinical data from high-volume units may provide pilot data for randomised trials. METHODS: Medical records from a tertiary hospital in Sydney, Australia, were analysed to identify all patients with resectable or borderline resectable PDAC. Data regarding treatment, toxicity and survival were collected. RESULTS: Between January 1 2010 and April 1 2016, 220 sequential patients were treated: 87 with NA and 133 with upfront operation (UO). Forty-three NA patients (52%) and 5 UO patients (4%) were borderline resectable at diagnosis. Twenty-four borderline patients received NA RT, 22 sequential to NAC. The median overall survival (OS) in the NA group was 25.9 months (mo); 95% CI (21.1-43.0 mo) compared to 26.9 mo (19.7, 32.7) in the UO; HR 0.89; log-ranked p-value = 0.58. Sixty-nine NA patients (79%) were resected, mOS was 29.2 mo (22.27, not reached (NR)). Twenty-two NA (31%) versus 22 UO (17%) were node negative at operation (N0). In those managed with NAC/RT the mOS was 29.0 mo (17.3, NR). There were no post-operative deaths with NA within 90-days and three in the UO arm. DISCUSSION: This is a hypothesis generating retrospective review of a selected real-world population in a high-throughput unit. Treatment with NA was well tolerated. The long observed survival in this group may be explained by lymph node sterilisation by NA, and the achievement of R0 resection in a greater proportion of patients.

Characterizing the Pattern of Anomalies in Congenital Zika Syndrome for Pediatric Clinicians.

Importance: Zika virus infection can be prenatally passed from a pregnant woman to her fetus. There is sufficient evidence to conclude that intrauterine Zika virus infection is a cause of microcephaly and serious brain anomalies, but the full spectrum of anomalies has not been delineated. To inform pediatric clinicians who may be called on to evaluate and treat affected infants and children, we review the most recent evidence to better characterize congenital Zika syndrome. Observations: We reviewed published reports of congenital anomalies occurring in fetuses or infants with presumed or laboratory-confirmed intrauterine Zika virus infection. We conducted a comprehensive search of the English literature using Medline and EMBASE for Zika from inception through September 30, 2016. Congenital anomalies were considered in the context of the presumed pathogenetic mechanism related to the neurotropic properties of the virus. We conclude that congenital Zika syndrome is a recognizable pattern of structural anomalies and functional disabilities secondary to central and, perhaps, peripheral nervous system damage. Although many of the components of this syndrome, such as cognitive, sensory, and motor disabilities, are shared by other congenital infections, there are 5 features that are rarely seen with other congenital infections or are unique to congenital Zika virus infection: (1) severe microcephaly with partially collapsed skull; (2) thin cerebral cortices with subcortical calcifications; (3) macular scarring and focal pigmentary retinal mottling; (4) congenital contractures; and (5) marked early hypertonia and symptoms of extrapyramidal involvement. Conclusions and Relevance: Although the full spectrum of adverse reproductive outcomes caused by Zika virus infection is not yet determined, a distinctive phenotype-the congenital Zika syndrome-has emerged. Recognition of this phenotype by clinicians for infants and children can help ensure appropriate etiologic evaluation and comprehensive clinical investigation to define the range of anomalies in an affected infant as well as determine essential follow-up and ongoing care.

Iodine status and thyroid function among Spanish schoolchildren aged 6-7 years: the Tirokid study.

I deficiency is still a worldwide public health problem, with children being especially vulnerable. No nationwide study had been conducted to assess the I status of Spanish children, and thus an observational, multicentre and cross-sectional study was conducted in Spain to assess the I status and thyroid function in schoolchildren aged 6-7 years. The median urinary I (UI) and thyroid-stimulating hormone (TSH) levels in whole blood were used to assess the I status and thyroid function, respectively. A FFQ was used to determine the consumption of I-rich foods. A total of 1981 schoolchildren (52 % male) were included. The median UI was 173 µg/l, and 17·9 % of children showed UI<100 µg/l. The median UI was higher in males (180·8 v. 153·6 µg/l; P<0·001). Iodised salt (IS) intake at home was 69·8 %. IS consumption and intakes of ≥2 glasses of milk or 1 cup of yogurt/d were associated with significantly higher median UI. Median TSH was 0·90 mU/l and was higher in females (0·98 v. 0·83; P<0·001). In total, 0·5 % of children had known hypothyroidism (derived from the questionnaire) and 7·6 % had TSH levels above reference values. Median TSH was higher in schoolchildren with family history of hypothyroidism. I intake was adequate in Spanish schoolchildren. However, no correlation was found between TSH and median UI in any geographical area. The prevalence of TSH above reference values was high and its association with thyroid autoimmunity should be determined. Further assessment of thyroid autoimmunity in Spanish schoolchildren is desirable.

Influence of white matter MRI hyper-intensities on acute l-dopa response in patients with Parkinson's disease.

OBJECTIVE: To determine whether brain white matter hyperintensities (WMH) influence l-dopa response in Parkinson's disease (PD) patients. METHODS: We prospectively evaluated 60 PD patients with an acute l-dopa challenge test, and assessed motor performance with the Movement Disorders Society revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS) during "ON" and "OFF" medication states. Magnetic resonance images were examined using a visual semi-quantitative rating scale for quantification and distribution analysis of WMH. l-dopa challenge test response was correlated to extent and location of WMH, to determine a potential association between them. RESULTS: Subjects with greater deep WMH burden, showed less response to l-dopa on axial motor symptoms (R = -0.35; p < 0.027), when tested with Part III of the MDS-UPDRS before and after acute levodopa challenge. CONCLUSIONS: Results suggest WMH may affect response to l-dopa on axial function of PD patients, which could be due to either non-dopaminergic (cortico-basal ganglia) motor pathway disruption, or postsynaptic nigrostriatal pathway involvement.

Transverse closure of mesenterico-portal vein after vein resection in pancreatoduodenectomy.

BACKGROUND: Resection of the involved mesenteric-portal vein (MPV) is increasingly performed in pancreatoduodenectomy. The primary aim of this study is to assess the rate of R0 resection in transverse closure (TC) versus segmental resection with end-to-end (EE) closure and the secondary aims are to assess the short-term morbidity and long-term survival of TC versus EE. METHODS: Patients undergoing pancreatoduodenectomy with MPV resection were identified from a prospectively database. The reconstruction technique were examined and categorized. Clinical, pathological, short-term and long-term survival outcomes were compared between groups. RESULTS: 110 patients underwent PD with MPV resection of which reconstruction was performed with an end-to-end technique in 92 patients (84%) and transverse closure technique in 18 patients (16%). Patients undergoing transverse closure tended to have had a shorter segment of vein resected (≤2 cm) compared to the end-to-end (83% vs. 43%; P = 0.004) with no difference in R0 rate. Short-term morbidity was similar. The median and 5-year survival was 30.0 months and 18% respectively for patients undergoing transverse closure and 28.6 months and 7% respectively for patients undergoing end-to-end reconstruction (P = 0.766). CONCLUSION: Without compromising the R0 rate, transverse closure to reconstruct the mesenteric-portal vein is shown to be feasible and safe in the setting when a short segment of vein resection is required during pancreatoduodenectomy. Synopsis - We describe a vein closure technique, transverse closure, which avoids the need for a graft, or re-implantation of the splenic vein when resection of the mesenteric-portal vein confluence is required during pancreatoduodenectomy.

Maternal exposure to methotrexate and birth defects: a population-based study.

Methotrexate is an anti-folate medication that is associated with increased risk of multiple birth defects. Using data from the National Birth Defects Prevention Study, a case-control study of major birth defects in the United States, we examined mothers exposed to methotrexate. The study population included mothers of live-born infants without major birth defects (controls) and mothers of fetuses or infants with a major birth defect (cases), with expected dates of delivery between October 1997 and December 2009. Mothers of cases and controls were asked detailed questions concerning pregnancy history, demographic information, and exposures in a telephone interview. Approximately 0.06% (n = 16/27,623) of case and 0.04% (n = 4/10,113) of control mothers reported exposure to methotrexate between 3 months prior to conception through the end of pregnancy. Of the 16 case infants, 11 (68.8%) had a congenital heart defect (CHD). The observed CHDs included atrial septal defects, tetralogy of Fallot, valvar pulmonary stenosis, ventricular septal defects (VSDs), and total anomalous pulmonary venous return. One case infant had microtia in addition to a VSD and another had VACTER association. Exposed cases without a CHD had one of the following birth defects: cleft palate, hypospadias, congenital diaphragmatic hernia, or craniosynostosis. Based on a limited number of methotrexate-exposed mothers, our findings support recent case reports suggesting an association between early pregnancy exposure to methotrexate and CHDs. Because of the rarity of maternal periconceptional exposure to methotrexate, long-term, population-based case-control studies are needed to confirm these findings and better evaluate the association between methotrexate and birth defects.

Anacetrapib, a novel CETP inhibitor: pursuing a new approach to cardiovascular risk reduction.

Cholesteryl ester transfer protein (CETP) inhibition is a promising experimental strategy to raise high-density lipoprotein cholesterol (HDL-C) and reduce cardiovascular risk. This review focuses on the highly selective and potent CE TP inhibitor anacetrapib and discusses the available preclinical and clinical information pertaining to it. We also describe strategies to target HDL-C, discuss the mechanism underlying CETP inhibition and its effects on lipid biology, and give an overview of other CETP inhibitors that are currently in development.

Skin to calcaneus distance in the neonate.

BACKGROUND: Current recommendations for obtaining blood from neonates advise avoidance of the midline area of the heel and are based on postmortem studies. OBJECTIVE: Because of the potential pain and tissue damage from repeated heel pricking in the same area, to investigate using ultrasonography whether the distance from skin to calcaneus is less at the midline than at the borders. METHODS: One hundred consecutive healthy preterm and 105 consecutive healthy term neonates were studied 48-72 hours after delivery. The skin to perichondrium distance (SPD) was measured on two occasions by ultrasound at the external, midline, and internal areas of the heel. FINDINGS: Mean SPD was 0.2 mm less at the midline than at the other sites. The proportion of measurements <3 mm at any of the three sites was the same. Depth was <3 mm in less than 3% of the term and approximately 20% of the preterm infants. The SPD correlated only with gestational age. Of children <33 weeks gestational age, 38% had an SPD <3 mm compared with 8% of older preterm infants. The proportions of preterm infants of > or = 33 weeks gestation and term infants with an SPD <3 mm were similar (8% v 3%). INTERPRETATION: With the use of automated lancets of 2.2 mm length or less, the whole heel plantar surface is safe for obtaining blood in term and preterm infants of > or = 33 weeks gestation. This means that soft tissue damage and pain from repeated pricking in the same area can be reduced.

Traumatismo medular neonatal y neuroimagen / Neonatal spinal cord injury and neuroimaging

No disponible

Acerca de los indicadores de la deficiencia nutricional de yodo / A propos of markers of iodine deficiency

No disponible

Analysis of phenol in an over-the-counter sore throat spray by cyclic voltammetry.

A method for analyzing phenol in an over-the-counter sore throat spray by cyclic voltammetry was developed. The method employed a glassy-carbon disk electrode (3 mm diameter) as the working electrode and 0.1 M HCl as the supporting electrolyte. The reference electrode was a silver-silver chloride electrode with 3 M NaCl. In the cyclic voltammetry procedure, the initial potential was +200 mV and the final potential was +1450 or +1500 mV. The cyclic voltammetric method was validated against a method based on reversed-phase high-performance liquid chromatography (HPLC). The phenol results for cyclic voltammetry at 50 mVs(-1) were in good agreement with the results obtained from HPLC. The results also agreed with the label claim (1.4% phenol). Good reproducibility and accuracy were obtained for the voltammetric method. Cyclic voltammetry was shown to be an accurate, reproducible, and rugged technique for the routine analysis of phenol in a sore throat spray.

Drug-resistant Drosophila indicate glutamate-gated chloride channels are targets for the antiparasitics nodulisporic acid and ivermectin.

The fruit fly Drosophila melanogaster was used to examine the mode of action of the novel insecticide and acaricide nodulisporic acid. Flies resistant to nodulisporic acid were selected by stepwise increasing the dose of drug in the culture media. The resistant strain, glc(1), is at least 20-fold resistant to nodulisporic acid and 3-fold cross-resistant to the parasiticide ivermectin, and exhibited decreased brood size, decreased locomotion, and bang sensitivity. Binding assays using glc(1) head membranes showed a marked decrease in the affinity for nodulisporic acid and ivermectin. A combination of genetics and sequencing identified a proline to serine mutation (P299S) in the gene coding for the glutamate-gated chloride channel subunit DmGluClalpha. To examine the effect of this mutation on the biophysical properties of DmGluClalpha channels, it was introduced into a recombinant DmGluClalpha, and RNA encoding wild-type and mutant subunits was injected into Xenopus oocytes. Nodulisporic acid directly activated wild-type and mutant DmGluClalpha channels. However, mutant channels were approximately 10-fold less sensitive to activation by nodulisporic acid, as well as ivermectin and the endogenous ligand glutamate, providing direct evidence that nodulisporic acid and ivermectin act on DmGluClalpha channels.

A new X linked mental retardation (XLMR) syndrome with short stature, small testes, muscle wasting, and tremor localises to Xq24-q25.

METHODS: A large family is described in which mental retardation segregates as an X linked trait. Six affected males in three generations were studied by linkage and clinical examination. RESULTS: Characteristic clinical features include short stature, prominent lower lip, small testes, muscle wasting of the lower legs, kyphosis, joint hyperextensibility, abnormal gait, tremor, and decreased fine motor coordination. Affected subjects also had impaired speech and decreased attention span. A carrier female was mildly affected. A similar disorder was not found on review of our XLMR Database of 124 syndromes. Linkage analysis of 37 markers resulted in a lod score of 2.80 at DXS1212 and 2.76 at DXS425. The limiting markers were DXS424 and DXS1047. Ten of 124 XLMR syndromes and eight of 58 MRX families overlap this region. CONCLUSIONS: In summary, this family appears to have a new XLMR syndrome localising to Xq24-q25.

Nonplatelet effects of aspirin during acute coronary occlusion: electrophysiologic and cation alterations in ischemic myocardium.

BACKGROUND: Mortality after acute myocardial ischemia has been reduced by aspirin (ASA) but mechanisms other than the antiplatelet effect have not been established. This article evaluates an antiarrhythmic action during sympathetic stimulation in the intact anesthetized dog with and without ischemia. METHODS AND RESULTS: The ventricular fibrillation threshold (VFT) was examined before and after epinephrine (E) in normals (group I). A VFT reduction during E was normalized after 1 week of ASA (P<.01). Regional myocardial ischemia for 1 hour resulted in similar hypoperfusion in controls of group II and after ASA. Action potential responses in isolated superfused ischemic tissue showed prolonged repolarization (APD90) in response to E, which was normalized after ASA (P<.01). To assess the antiarrhythmic role of the anion in group III, Na salicylate was given. During 1 hour of ischemia, the VF incidence was reduced and cation abnormalities diminished in ischemic myocardium compared with untreated ischemia. CONCLUSIONS: ASA antagonizes the reduction of the VFT induced by catecholamine in normals as well as the repolarization abnormality elicited by E during acute ischemia. The salicylate anion appears to be the active component in view of the efficacy in preventing VF during the early ischemic period.

XLMR database.

The computer database on X-linked mental retardation (XLMR) disorders developed by Arena and Lubs in 1991 has now been updated to include all currently known XLMR disorders and nonspecific (MRX) families. Currently, it includes 123 syndromes, 59 nonspecific XLMR families, and 60 families from the Miami/Greenwood study. The older clinical reports have been reviewed and revised. The search mechanism has also been revised and now includes 740 individual "keywords." Each of these keywords recognizes several of clinical descriptive terms, as used in published literature reports. Searches can be made according to any clinical finding or combination of findings. For each disorder, the database presents a graphic display that contains a revised and more complete set of clinical findings, references, keywords, map localization, molecular information, access to pictures, and OMIM number.