Holotranscobalamin Is a Useful Marker of Vitamin B12 Deficiency in Alcoholics

Background. Measurement of serum cobalamin (Cbl) levels is the standard investigation for assessing vitamin B12 deficiency. Falsely increased values of Cbl can be caused by alcoholic liver disease. Measurement of total vitamin B12 serum levels might be misleading in alcoholics, because a tissue metabolic deficiency is possible even with normal serum Cbl levels. Holotranscobalamin (HoloTC), the Cbl metabolically active fraction, is considered as a better index of vitamin B12 deficiency. Methods. For assessing vitamin B12 status, we evaluated 22 adult alcoholic male patients by measuring in parallel serum Cbl, serum folate and red blood cell folate levels, HoloTC levels by the AxSYM assay. Results. HoloTC values were reduced in 3 alcoholics with borderline-low Cbl values. Significant positive correlations were found between serum Cbl and HoloTC levels, serum Cbl and gamma-glutamyl transpeptidase (GGT). Conclusion. HoloTC measurement is a useful option for assessing vitamin B12 status in alcoholics, particularly in the subjects with borderline Cbl values and may be considered an early marker of vitamin B12 deficiency

Down Regulation of High in Normal-1 (<b> <i>HIN-1</i> </b>) is a Frequent Event in Stage I Non-Small Cell Lung Cancer and Correlates with Poor Clinical Outcome

Abstract Purpose: The aim of this study was to evaluate the prevalence and the clinical significance of HIN-1 mRNA expression in early stage non-small cell lung carcinomas (NSCLCs). Experimental Design: A series of 91 NSCLC patients with stage I neoplastic disease was studied. HIN-1 expression was investigated by quantitative real-time reverse transcription-PCR on tumor specimens and matching normal lung tissues. Variables were analyzed by χ2 test and Fisher's exact tests. Survival was evaluated with the method of Kaplan-Meier. Multivariate analysis was performed with Cox's proportional hazards model. Results: Seventy one (78%) tumors showed a reduction of HIN-1 mRNA compared with the normal counterpart. The range of reduction varied greatly, from −2-fold to −3350-fold. Setting a cutoff at −46-fold (median value of HIN-1 mRNA reduction), 46 cases (51%) had a markedly reduced expression, and 45 cases (49%) showed a normal or slightly reduced expression. A statistically significant association between low HIN-1 mRNA levels and T status was observed (P = 0.036). Univariate survival curves, estimated using the method of Kaplan-Meier, defined a significant association between HIN-1 expression and both overall survival (P = 0.0095) and disease-free survival (P = 0.0122). A multivariate analysis, performed by Cox's proportional hazards regression model, confirmed that a low HIN-1 expression was the only significant factor to predict poor prognosis. Conclusions: Our data indicate that HIN-1 expression, measured by real-time reverse transcription-PCR, is a possible prognostic factor in patients with stage I NSCLC. Additional studies are required to further validate this potential prognostic marker

Oesophageal stenosis due to heterotopy of gastric mucosa: a rare case of dysphagia in paediatric age

We describe the case of a three-year-old child who presents recurrent vomiting, dysphagia for solids, and weight deficit. Besides the poor general clinical conditions, the kid presents also retrosternal pyrosis. The laboratory tests show the presence of sideropenic anaemia, but it is possible to make a diagnosis only after endoscopy of the superior gastrointestinal tract, which reveals a chronic inflammation due to heterotopy of gastric mucosa. In the suspect of this kind of disease, this test should always be performed, and, if the proton pump inhibitors (PPIs) aren't effective enough, the Savary-Gilliard® dilators provide a safe and effective therapeutic solution

Multi-Center Randomized Phase II Clinical Trial on Remote Ischemic Conditioning in Acute Ischemic Stroke Within 9 Hours of Onset in Patients Ineligible to Recanalization Therapies (TRICS-9): Study Design and Protocol

Aim: To assess the efficacy of remote ischemic conditioning (RIC) in patients with ischemic stroke within 9 h of onset, that are not candidates for recanalization therapies.Sample Size Estimates: A sample size of 80 patients (40 in each arm) should yield 80% power to detect a 20% difference in early neurological improvement at 72 h at p = 0.05, two sided.Methods and Design: TRICS-9 is a phase II, multicenter, controlled, block randomized, open-label, interventional clinical trial. Patients recruited in Italian academic hospitals will be randomized 1:1 to either RIC plus standard medical therapy or standard medical therapy alone. After randomization, RIC will be applied manually by four alternating cycles of inflation/deflation 5 min each, using a blood pressure cuff around the non-paretic arm.Study Outcomes: The primary efficacy outcome is early neurological improvement, defined as the percent change in the National Institute of Health Stroke Scale (NIHSS) at 72 h in each arm. Secondary outcomes include early neurologic improvement at 24 and 48 h, disability at 3 months, rate of symptomatic intracerebral hemorrhage, feasibility (proportion of patients completing RIC), tolerability after RIC and at 72 h, blood levels of HIF-1 alpha, and HSP27 at 24 h and 72 h.Discussion/Conclusion: RIC in combination with recanalization therapies appears to add no clinical benefit to patients, but whether it is beneficial to those that are not candidates for recanalization therapies is still to be demonstrated. TRICS-9 has been developed to elucidate this issue

Increased expression of pro-angiogenic factors and vascularization in thyroid hyperfunctioning adenomas with and without TSH receptor activating mutations

Autonomously functioning thyroid nodules (AFTN) are known to receive an increased blood influx necessary to sustain their high rate of growth and hormone production. Here, we investigated the expression of hematic and lymphatic vases in a series of 20 AFTN compared with the contralateral non-tumor tissues of the same patients, and the transcript levels of proteins involved in the control of vascular proliferation, including the vascular endothelial growth factor (VEGF) and platelet-derived growth factors (PDGF) and their receptors and the endothelial nitric oxide synthase (eNOS). In parallel, the expression of the differentiation markers sodium/iodide symporter (NIS), thyroperoxidase (TPO), thyroglobulin (Tg), and TSH receptor (TSHR) was also investigated. The data were further analyzed comparing subgroups of tumors with or without mutations in the TSHR gene. Analysis by means of CD31 and D2-40 immunostaining showed in AFTN an increased number of hematic, but not lymphatic, vessels in parallel with an enhanced proliferation rate shown by increased Ki67 staining. Quantitative RT-PCR analysis revealed an increase of VEGF, VEGFR1 and 2, PDGF-A, PDGF-B, and eNOS expression in tumor versus normal tissues. Also, higher transcript levels of NIS, TPO, and Tg were detected. Comparison of the two subgroups of samples revealed only few differences in the expression of the genes examined. In conclusion, these data demonstrate an increased expression of angiogenesis-related factors associated with an enhanced proliferation of hematic, but not lymphatic, vessels in AFTNs. In this context, the presence of TSHR mutations may only slightly influence the expression of pro-angiogenic growth factors

Early hemispherectomy in catastrophic epilepsy A neuro-cognitive and epileptic long-term follow-up

SummaryThe authors report their experience about a neuro-cognitive and epileptic long-term follow-up of children with catastrophic epilepsy treated with hemispherectomy in the first 5 years of life.Nineteen children with resistant epilepsy that significantly interfered with their neuro-cognitive development underwent hemispherectomy within 5 years of life (mean: 2 years, 3 months; range: 5 months to 5 years). All patients were assessed before surgery and after, at least at the end of the follow-up (mean: 6 years and 6 months; range: 2–11 years and 2 months) with a full clinical examination including motor ability and functional status evaluation as well as behaviour observation, neuroimaging and an ictal/interictal prolonged scalp video-EEG.A seizure-free outcome was obtained in 73.7% of patients. Gross motility generally improved and cognitive competence did not worsen, with an evident progress in two cases.Consistently with previous reports, evolution was worse in cortical dysplasia than in progressive or acquired vascular cerebropathies. The excellent epileptic outcome and the lack of developmental deterioration in comparison with other more aged series seem to suggest a possible better evolution in earlier surgery treatment. To confirm this suggestion, however, further experience with larger series is needed

Clinical characteristics of a large cohort of patients with narcolepsy candidate for pitolisant: a cross-sectional study from the Italian PASS Wakix® Cohort

Introduction Narcolepsy is a chronic and rare hypersomnia of central origin characterized by excessive daytime sleepiness and a complex array of symptoms as well as by several medical comorbidities. With growing pharmacological options, polytherapy may increase the possibility of a patient-centered management of narcolepsy symptoms. The aims of our study are to describe a large cohort of Italian patients with narcolepsy who were candidates for pitolisant treatment and to compare patients' subgroups based on current drug prescription (drug-naive patients in whom pitolisant was the first-choice treatment, switching to pitolisant from other monotherapy treatments, and adding on in polytherapy). Methods We conducted a cross-sectional survey based on Italian data from the inclusion visits of the Post Authorization Safety Study of pitolisant, a 5-year observational, multicenter, international study. Results One hundred ninety-one patients were enrolled (76.4% with narcolepsy type 1 and 23.6% with narcolepsy type 2). Most patients (63.4%) presented at least one comorbidity, mainly cardiovascular and psychiatric. Pitolisant was prescribed as an add-on treatment in 120/191 patients (62.8%), as switch from other therapies in 42/191 (22.0%), and as a first-line treatment in 29/191 (15.2%). Drug-naive patients presented more severe sleepiness, lower functional status, and a higher incidence of depressive symptoms. Conclusion Our study presents the picture of a large cohort of Italian patients with narcolepsy who were prescribed with pitolisant, suggesting that polytherapy is highly frequent to tailor a patient-centered approach

Nutrition in preschool children and later risk of obesity: a systematic review and meta analysis

Objectives and study: Nutrition in infants and preschool children has been suggested to influence the risk of later obesity. However, the evidence for this association is conflicting and few studies have investigated this prospectively or considered the role of energy and specific macronutrients. Here we report a systematic review and meta-analyis of studies that tested the hypothesis that nutrition in the preschool period, between the ages of 6 months and 3 years, is associated with later obesity risk. Methods: MEDLINE, EMBASE and CENTRAL databases were searched from January 1988 to June 2015 for studies reporting nutritional intake in infants and preschool children aged 6-36 months and later measures of obesity. Bibliographies of included studies were hand searched and authors and other experts consulted to identify omissions. We included all studies that investigated dietary energy and/or macronutrient intake during 6-36 months in relation to later measures of obesity. Methodological quality was assessed using the Downs and Black checklist designed specifically to appraise both randomised and non-randomised studies. The checklist was adapted to include aspects of particular relevance to studies investigating nutritional exposures. Two reviewers independently scored studies against the 28 item checklist which included questions on study reporting, external validity, internal validity (bias and confounding), and statistical power. A statistician independently scored questions relating to statistical methods and their decision was final. Data from studies amenable to meta-analysis were analysed using STATA (StataCrop 12, Texas). For continuous outcomes, results were expressed as standardised mean difference (SMD) between the high and low protein intake groups. For dichotomous outcomes, results for each study were expressed as relative risk (RR). Both dichotomous and continuous outcomes were presented with 95% confidence intervals (CI). Between-study heterogeneity was assessed by the Q and I2 statistics. Results: 24 eligible articles (comprising 16 primary studies) were included in a narrative synthesis, and 13 studies in a random-effects meta-analysis. A higher protein intake was associated with later risk of obesity in 15 studies. In 13 studies included in the meta-analysis protein in the preschool period was associated with higher BMI z-score later in childhood (pooled effect size: 0.28 z-scores, 95% CI 0.20 to 0.35)(Figure 1). There was no significant hererogeneity between studies (I2 0.0%, p = 0.932). Associations of energy, fat and carbohydrate were inconclusive. Conclusion: Our findings suggest that nutrition and particularly high protein intake in infants and preschool children is important for risk of later obesity. Although further experimental data are required to establish causality, these findings suggest that optimising the protein intake of these children could be important for their long term health

Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study

Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA2DS2-VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0–1.3] for each point increase; P=0.05) and hypertension (OR, 2.3 [95% CI, 1.0–5.1]; P=0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0–1.2] for each year increase; P=0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4–14.2]; P=0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4–5.5]; P=0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8–1.7]). Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding

The risk of stroke recurrence in patients with atrial fibrillation and reduced ejection fraction

Abstract Background: Atrial fibrillation (AF) and congestive heart failure often coexist due to their shared risk factors leading to potential worse outcome, particularly cerebrovascular events. The aims of this study were to calculate the rates of ischemic and severe bleeding events in ischemic stroke patients having both AF and reduced ejection fraction (rEF) (⩽40%), compared to ischemic stroke patients with AF but without rEF. Methods: We performed a retrospective analysis that drew data from prospective studies. The primary outcome was the composite of either ischemic (stroke or systemic embolism), or hemorrhagic events (symptomatic intracranial bleeding and severe extracranial bleeding). Results: The cohort for this analysis comprised 3477 patients with ischemic stroke and AF, of which, 643 (18.3%) had also rEF. After a mean follow-up of 7.5 ± 9.1 months, 375 (10.8%) patients had 382 recorded outcome events, for an annual rate of 18.0%. While the number of primary outcome events in patients with rEF was 86 (13.4%), compared to 289 (10.2%) for the patients without rEF; on multivariable analysis rEF was not associated with the primary outcome (OR 1.25; 95% CI 0.84–1.88). At the end of follow-up, 321 (49.9%) patients with rEF were deceased or disabled (mRS ⩾3), compared with 1145 (40.4%) of those without rEF; on multivariable analysis, rEF was correlated with mortality or disability (OR 1.35; 95% CI 1.03–1.77). Conclusions: In patients with ischemic stroke and AF, the presence of rEF was not associated with the composite outcome of ischemic or hemorrhagic events over short-term follow-up but was associated with increased mortality or disability