Chromosome 3p alterations in pancreatic endocrine neoplasia

Pancreatic endocrine tumors (PET) are rare neoplasms classified as functioning (F-PET) or non-functioning (NF-PET) according to the presence of a clinical syndrome due to hormonal hypersecretion. PETs show variable degrees of clinical aggressiveness and loss of chromosome 3p has been suggested to be associated with an advanced stage of disease. We assessed chromosome 3p copy number in 113 primary PETs and 32 metastases by fluorescence in situ hybridization (FISH) using tissue microarrays. The series included 56 well-differentiated endocrine tumors (WDET), 62 well-differentiated endocrine carcinomas (WDEC), and 6 poorly differentiated endocrine carcinomas (PDEC). Chromosome 3p alterations were found in 23/113 (20%) primary tumors, with losses being predominant over gains (14% vs. 6%). Loss of 3p was found in 5/55 (9%) WDET, 11/52 (21%) WDEC, and never in PDEC. Gains of 3p were detected in 4/55 (7%) WDET, no WDEC, but notably in 3/6 (50%) PDEC (OR 23.6; P = 0.003). Metastases were more frequently monosomic for 3p compared to primary tumors (OR 3.6; P = 0.005). Monosomy was significantly associated with larger tumor size, more advanced tumor stage, and metastasis. No association was found with survival. Chromosome 3p copy number alterations are frequent events in advanced stage PET, with gains prevailing in PDEC while losses are more frequent in WDEC, supporting the view that a specific pattern of alterations are involved in these diverse disease subtypes

Combined inguinal hernia in the elderly. Portraying the progression of hernia disease

Introduction: Identification of a combined hernia is a common occurrence in the course of inguinal hernia repair. This type of protrusion disease seems to affect the elderly, in particular. Very few investigations have been carried out to ascertain the structural changes that occur in the groin affected by this clinical condition. Method: Analysis of intraoperative findings of combined inguinal hernias evidenced in the elderly, from the most recent 100 groin hernia repair procedures carried out by a single operator, represents the basis of the article. Protrusions that presumably represent the forerunner of this type of hernia were also analyzed: double ipsilateral inguinal hernias composed of a direct and an indirect protrusion. The gross anatomical, as well as histological, modifications occurring during the development of combined protrusions were also evaluated. Results: Combined hernia was the most frequent protrusion in patients over 65 years, accounting for 36% of the total in this patient group. In the same patient cohort, double inguinal hernia further involves 22% of elderly subjects. Macroscopically, progressive disruption of the inguinal back wall and degenerative reabsorption of the inferior epigastric vessels were evidenced. Histologically, inflammatory infiltrate, significant nerve and vascular injuries, along with severe muscle degeneration were recognized. Conclusions: The results seem to confirm that inguinal hernia is an unremitting progressive disease caused by chronic compressive structural damage. Combined hernias represent a frequent clinical condition in the elderly consequent to long-term degenerative damage. Therapy of combined protrusions must consider the impact of visceral vector forces

RASSF1 tumor suppressor gene in pancreatic ductal adenocarcinoma: correlation of expression, chromosomal status and epigenetic changes

Background: The Ras Association Domain Family Member 1 (RASSF1) is one of the most frequently reported methylation-inactivated tumor suppressor genes in primary pancreatic ductal adenocarcinomas (PDAC). Limited information is still available about the impact of RASSF1 gene silencing on the expression of its different isoforms in neoplastic cells. Methods: A series of 96 primary PDAC, with known clinico-pathological parameters, was tested for RASSF1 methylation status by methylation-specific PCR, RASSF1 locus copy number alterations by fluorescence in situ hybridization, and Rassf1a protein expression by immunohistochemistry. A further series of 14 xenografted primary PDAC and 8 PDAC-derived cell lines were tested to obtain a detailed methylation mapping of CpG islands A and C of the RASSF1 locus by pyrosequencing and to evaluate the expression of Rassf1 variants by qRT-PCR. Results: Methylation of CpG island A of the RASSF1 gene was observed in 35% of the tumors and allelic loss of RASSF1 locus was seen in 30 disomic and in 20 polysomic cases (52%). Rassf1a immunohistochemical expression was downregulated in half of primary PDAC, and this downregulation was neither correlated with methylation of RASSF1 promoter nor with RASSF1 copy number alterations. RASSF1 status did not influence patients' prognosis. The expression of the seven RASSF1 isoforms in xenografts and cell lines showed that RASSF1A, RASSF1B, and RASSF1C isoforms were present in all xenografts and cell lines, whereas RASSF1D, RASSF1E, and RASSF1F isoforms were variably expressed among samples. RASSF1G was never expressed in either xenografts or cell lines. The variable expression of RASSF1 isoforms in PDAC xenografts and cell lines was not dependent on RASSF1 methylation status of CpG islands A and C. Conclusions:RASSF1 alterations occurring in PDAC mainly consist in variations of expression of the different isoforms. Different genetic mechanisms seem to contribute to RASSF1 deregulation in this setting, but RASSF1 methylation does not seem to substantially affect RASSF1 isoforms expression

CISTACANTOS DE GIGANTORHYNCHUS ECHINODISCUS (ACANTHOCEPHALA, GIGANTORHYNCHIDAE), EN TERMITAS NEOTROPICALES (ISOPTERA, TERMITIDAE)

Specimens of Labiotermes emersoni (Araujo, 1954) and Orthognathotermes heberi Raw & Egler, 1985, were collected at Parque Nacional da Serra da Canastra, State of Minas Gerais, Brazil. Soldiers of the two species were suspected to carry larval acanthocephalan parasites due to different sizes and shape of their heads and because some specimens had a conspicuous, cylindrical, whitish 'body' in the hemocoel, around the digestive tract in the abdomen. The termites showed shape alteration and light pigmentation dystrophy of the heads induced by the larval acanthocephalans. These alterations were documented photographically and the cystacanths described. The encysted juveniles removed from the hemocoel of infected soldier termites and processed accordingly, were determined as Gigantorhynchus echinodiscus (Diesing, 1851). The proboscis had the typical cylindrical shape and the characteristic two distal circles of large hooks (6+12), covered with small, almost rootless spines, and a very short neck. This is the first record from Brazil of any species of termites infected with acanthocephalans of the genus Gigantorhynchus Hamann, 1892 and the first record of G. echinodiscus cystacanths infecting the intermediate host.Los especímenes de Labiotermes emersoni (Araujo, 1954) y Orthognathotermes heberi Raw & Egler, 1985, se colectaron en el Parque Nacional de Serra da Canastra, Estado de Minas Gerais, Brasil. Se sospechaba que soldados de las dos especies eran portadores de larvas de acantocéfalos parásitos debido a diferentes tamaños y formas de la cabeza, además de un “cuerpo” blanquecino, cilíndrico visible en el hemocele de algunos ejemplares, alrededor del tubo digestivo en el abdomen. Los termitas mostraron alteración de forma y leve distrofia de pigmentación en sus cabezas inducidas por los acantocéfalos larvales. Estas alteraciones se documentaron fotográficamente y se describen los cistacantos. Las formas juveniles enquistadas retiradas del hemocele de soldados infectados se identificaron como Gigantorhynchus echinodiscus (Diesing, 1851). Los probóscides tenían la típica forma cilíndrica y los característicos dos círculos distales de grandes ganchos (6+12), cubiertos de pequenas espinas, casi sin raíces y un cuello muy corto. Este es el primer registro de dos especies de termitas infectadas por acantocéfalos del género Gigantorhynchus Hamann, 1892 y el primero registro de cistacantos de G. echinodiscus infectando el hospedero intermediário

Sedentary behavior : a key component in the interaction between an integrated lifestyle approach and cardiac autonomic function in active young men

This study aimed to verify the association between autonomic cardiac function (CAF) and the integration of caloric expenditure by physical activity (PA) intensity, sedentary behavior (SB), and sleep quality (PSQI) in active young men. Thirty-five subjects were included, and caloric expenditure in moderate-to-vigorous and light-intensity PA, SB, and PSQI were assessed using questionnaires. Heart rate variability (HRV) was recorded for short periods of time in the supine and orthostatic positions. Multiple linear regression was realized unadjusted and adjusted for covariables, such as age, body mass index, and fat mass. No adjusted analysis indicated that, in the supine position, there were negative associations between the SB and the TP, HF, and NorHF indices, and positive associations between SB and NorLF and LF/HF. In the orthostatic position, an interaction between SB and NorLF was found. Significance of proportion with the TP, HF, and LF/HF indices was confirmed. When adjusted, for the supine position, negative interactions were documented between SB and the TP as well as the HF indices, and between PSQI and the LF/HF index, with interference under the HF and LF/HF indices. Finally, our findings indicate that the proposed approach interacts with CAF, and SB is significantly related to CAF in young active men

Time trend prevalence of artificial nutrition counselling in a university hospital.

Abstract Objectives The negative effects of malnutrition on the prognosis of hospitalized patients are well documented; however, less known is the awareness and knowledge of health care professionals about this complication. The aim of this study was to evaluate the trend of the requests for nutritional consultation in years and the prescription of artificial nutrition (AN), for adult patients at a university hospital in southern Italy in the years 2004, 2008, 2012, and 2016 to assess the progress of medical teams concerning awareness of hospital malnutrition. Methods This was a retrospective study that evaluated the time trend of nutritional consultation requests and related prescription of AN, for adult patients at a university hospital in southern Italy in the years 2004, 2008, 2012, and 2016. Of 112 233 inpatients, 2505 received a nutritional consultation with the prescription of AN. Results The number of patients on AN increased from 507 of 33 240 (1.52%) in 2004 to 730 of 29 195 (2.5%) in 2008 (P The request for AN was quite equally distributed between surgical (51.5%) and medical wards (48.5%), with a prevalence among patients with oncologic diseases (806 patients [65.6%]). As for nononcologic diseases, 20.4% involved the gastrointestinal tract and 6.3% the nervous system. Throughout the 12 y of observation, parenteral nutrition was the main prescribed support (59.8%) followed by oral nutritional supplements (26.1%) and enteral nutrition (9.3%). Mean nutritional intervention duration was 11 d (±10.8 d). Conclusions The request of AN for hospitalized patients increased over time, probably owing to improved medical consciousness of the potential risks for malnutrition and the availability of a specialized clinical nutrition team

Methylation-associated down-regulation of RASSF1A and up-regulation of RASSF1C in pancreatic endocrine tumors

<p>Abstract</p> <p>Background</p> <p><it>RASSF1A </it>gene silencing by DNA methylation has been suggested as a major event in pancreatic endocrine tumor (PET) but <it>RASSF1A </it>expression has never been studied. The <it>RASSF1 </it>locus contains two CpG islands (<it>A </it>and <it>C</it>) and generates seven transcripts (<it>RASSF1A</it>-<it>RASSF1G</it>) by differential promoter usage and alternative splicing.</p> <p>Methods</p> <p>We studied 20 primary PETs, their matched normal pancreas and three PET cell lines for the (i) methylation status of the <it>RASSF1 </it>CpG islands using methylation-specific PCR and pyrosequencing and (ii) expression of <it>RASSF1 </it>isoforms by quantitative RT-PCR in 13 cases. CpG island A methylation was evaluated by methylation-specific PCR (MSP) and by quantitative methylation-specific PCR (qMSP); pyrosequencing was applied to quantify the methylation of 51 CpGs also encompassing those explored by MSP and qMSP approaches.</p> <p>Results</p> <p>MSP detected methylation in 16/20 (80%) PETs and 13/20 (65%) normal pancreas. At qMSP, 11/20 PETs (55%) and 9/20 (45%) normals were methylated in at least 20% of <it>RASSF1A </it>alleles.</p> <p>Pyrosequencing showed variable distribution and levels of methylation within and among samples, with PETs having average methylation higher than normals in 15/20 (75%) cases (<it>P </it>= 0.01). The evaluation of mRNA expression of <it>RASSF1 </it>variants showed that: i) <it>RASSF1A </it>was always expressed in PET and normal tissues, but it was, on average, expressed 6.8 times less in PET (<it>P </it>= 0.003); ii) <it>RASSF1A </it>methylation inversely correlated with its expression; iii) <it>RASSF1 </it>isoforms were rarely found, except for <it>RASSF1B </it>that was always expressed and <it>RASSF1C </it>whose expression was 11.4 times higher in PET than in normal tissue (<it>P </it>= 0.001). A correlation between <it>RASSF1A </it>expression and gene methylation was found in two of the three PET cell lines, which also showed a significant increase in <it>RASSF1A </it>expression upon demethylating treatment.</p> <p>Conclusions</p> <p><it>RASSF1A </it>gene methylation in PET is higher than normal pancreas in no more than 75% of cases and as such it cannot be considered a marker for this neoplasm. <it>RASSF1A </it>is always expressed in PET and normal pancreas and its levels are inversely correlated with gene methylation. Isoform <it>RASSF1C </it>is overexpressed in PET and the recent demonstration of its involvement in the regulation of the Wnt pathway points to a potential pathogenetic role in tumor development.</p

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension