Search

Currently there is great interest in developing clinical applications of platelet-rich plasma to enhance bone repair.To assess bone regeneration in mandibular fractures, with the application of this adjuvant.Twenty patients with mandibular fractures were included in a randomized clinical trial. Patients of the experimental group (n = 10) were submitted to internal fracture reduction and administration of platelet-rich plasma, and patients of the control group (n = 10) were submitted to the same surgical procedure without plasma application. Radiologic assessment was made before and at 1 and 3 months after surgery. X-rays were digitalized for analyze intensity and density as reflection of bone regeneration.The average age was 32 ± 11.3 years and 31.2 ± 8.48 years respectively (p = 0.76). The radiographic intensity and density in the experimental group at the 1The platelet-rich plasma increased the bone intensity and density in the fracture trace allowing bone regeneration and recovery in shorter time than patients in which it was not used.Actualmente existe interés en el desarrollo de aplicaciones clínicas del plasma rico en plaquetas (PRP) para mejorar la regeneración ósea (RO).Evaluar la RO en fracturas mandibulares con la aplicación de PRP.Ensayo clínico controlado. Se incluyeron 20 pacientes con fractura de ángulo mandibular. El grupo de estudio (n = 10) se sometió a reducción de la fractura, fijación interna y aplicación de PRP, y el grupo control (n = 10) al mismo procedimiento sin administración de plasma. Se evaluaron en el preoperatorio y al primer y tercer mes posterior a la reducción mediante digitalización radiográfica para evaluar la regeneración ósea.El promedio de edad fue de 32 ± 11.3 y 31.2 ± 8.48 años, respectivamente (p = 0.76). La intensidad y la densidad radiográfica al mes y a los 3 meses fueron superiores en el grupo de estudio que en el grupo control (p0.005). El tiempo de regeneración fue de 3.7 ± 0.48 y 4.5 ± 0.52 semanas, respectivamente (p = 0.002).El PRP aumentó la intensidad y la densidad ósea en el trazo de las fracturas, sugestivas de RO, y recuperación en menor tiempo, en contraste con el grupo control.

Introduction the frequency of distal femur fractures in the elderly is rapidly increasing. A study of these fractures was conducted in our center in order to evaluate the comorbidities and the mortality associated with this entity. Material and methods all the distal femur fractures by low energy in patients over 65 years old at a tertiary center were included, between January 2010 and December 2016. Baseline characteristics, the type of fracture, comorbidities, and functional status before admission, were collected. The relationship of each of these variables to the final functional class, immediate and late complications and mortality during the follow-up. Fifty-nine patients were included, with a median age of 85.3 years (IQR 78.6–91.6). Fifty-one patients were women. In 10 patients, the fractures were atraumatic (postural change mainly in non-walking patients), and in 54 of the cases were treated surgically (6 with retrograde intramedullary nailing and 48 with lateral locking plate). The median time to surgery was 4.5 days (IQR 2–6) and 14 patients were operated within 48 hours. The median follow-up was 26.3 months. Results fourteen patients died during the first year of follow-up. Factors independently associated with death during the first year after the fracture were: conservative treatment, and the inability to ambulate before the episode. The absence of certain comorbidities, such as chronic heart disease, and cancer, and an age under 80 years, behaved as protective factors. Conclusion low-energy distal femur fractures comprise a severe injury in the elderly and are associated with high mortality. Surgical treatment showed better outcomes in terms of survival, with no significant differences depending on the type of fracture, the type of implant or the median time to surgery.

INTRODUCTION: The safety of Helicobacter pylori eradication treatments and to what extent adverse events (AEs) influence therapeutic compliance in clinical practice are hardly known. Our aim was to assess the frequency, type, intensity, and duration of AEs, and their impact on compliance, for the most frequently used treatments in the European Registry on Helicobacter pylori management. METHODS: Systematic prospective non interventional registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H. pylori infection in routine clinical practice. All prescribed eradication treatments and their corresponding safety profile were recorded. AEs were classified depending on the intensity of symptoms as mild/moderate/severe and as serious AEs. All data were subject to quality control. RESULTS: The different treatments prescribed to 22, 492 patients caused at least 1 AE in 23% of the cases ; the classic bismuth-based quadruple therapy was the worst tolerated (37% of AEs). Taste disturbance (7 %) , diarrhea (7 %) , nausea (6%), and abdominal pain (3%) were the most frequent AEs. The majority of AEs were mild (57%), 6% were severe, and only 0.08% were serious, with an average duration of 7 days. The treatment compliance rate was 97%. Only 1.3% of the patients discontinued treatment due to AEs. Longer treatment durations were significantly associated with a higher incidence of AEs in standard triple, concomitant, bismuth quadruple, and levofloxacin triple or quadruple therapies. DISCUSSION: Helicobacter pylori eradication treatment frequently induces AEs, although they are usually mild and of limited duration. Their appearance does not interfere significantly with treatment compliance.

Methylation in CpG sites of the PPARGC1A gene (encoding PGC1-&alpha, ) has been associated with adiposity, insulin secretion/sensitivity indexes and type 2 diabetes. We assessed the association between the methylation profile of the PPARGC1A gene promoter gene in leukocytes with insulin secretion/sensitivity indexes in normoglycemic women. A standard oral glucose tolerance test (OGTT) and an abbreviated version of the intravenous glucose tolerance test (IVGTT) were carried out in n = 57 Chilean nondiabetic women with measurements of plasma glucose, insulin, and C-peptide. Bisulfite-treated DNA from leukocytes was evaluated for methylation levels in six CpG sites of the proximal promoter of the PPARGC1A gene by pyrosequencing (positions -816, -783, -652, -617, -521 and -515). A strong correlation between the DNA methylation percentage of different CpG sites of the PPARGC1A promoter in leukocytes was found, suggesting an integrated epigenetic control of this region. We found a positive association between the methylation levels of the CpG site -783 with the insulin sensitivity Matsuda composite index (rho = 0.31, p = 0.02) derived from the OGTT. The CpG hypomethylation in the promoter position -783 of the PPARGC1A gene in leukocytes may represent a biomarker of reduced insulin sensitivity after the ingestion of glucose.

Single nucleotide polymorphisms can create a genetic microenvironment in some tumors that affects the course of treatment, resistance, etc. Whether single nucleotide polymorphisms have an impact on gastrointestinal stromal tumor (GIST) development and disease progression is not yet accurately verified. KIT SNPM541L in exon 10 correlates with a worse prognosis of many cancers. The impact of KIT SNPM541L in GISTs is relatively unknown and, therefore, its analyses could have potential in patient therapy and could provide more detailed information on tumor character, clinical presentation, or tumor behavior in treatment. The aim of the study was the analysis of the biological and clinical significance of the KIT SNPM541L polymorphism in exon 10. Paraffin sample tissues were obtained from the National GIST Register in Martin. Retrospective samples from 177 GIST patients were divided into several groups. Detection of SNPM541L was performed by Sanger sequencing. Statisitical analyses were performed to determine the prevalence of KIT SNPM541L in the Slovak GIST cohort, to search for correlation between c-KIT status and clinicopathological, molecular and biological data. Overall, 29 samples out of 177 showed KIT SNPM541L polymorphism. Our results do not support the association between KIT SNPM541L and increased risk of relapse in localized primary GISTs. Additionally, we found a positive correlation between KIT SNPM541L occurrence and earlier onset of relapse in PDGFRa and WT subgroup of GISTs.

Objectives: The objective of this research was to understand physician, patient, and parent perspectives on barriers to second-generation antipsychotic (SGA) medication adherence in youth with bipo...

Different bismuth quadruple therapies containing proton-pump inhibitors, bismuth salts, metronidazole, and a tetracycline have been recommended as third-line Helicobacter pylori eradication treatment after failure with clarithromycin and levofloxacin.To evaluate the efficacy and safety of third-line treatments with bismuth, metronidazole, and either tetracycline or doxycycline.Sub-study with Spanish data of the "European Registry on H pylori Management" (Hp-EuReg), international multicenter prospective non-interventional Registry of the routine clinical practice of gastroenterologists. After previous failure with clarithromycin- and levofloxacin-containing therapies, patients receiving a third-line regimen with 10/14-day bismuth salts, metronidazole, and either tetracycline (BQT-Tet) or doxycycline (BQT-Dox), or single capsule (BQT-three-in-one) were included. Data were registered at AEG-REDCap database. Univariate and multivariate analyses were performed.Four-hundred and fifty-four patients have been treated so far: 85 with BQT-Tet, 94 with BQT-Dox, and 275 with BQT-three-in-one. Average age was 53 years, 68% were women. Overall modified intention-to-treat and per-protocol eradication rates were 81% (BQT-Dox: 65%, BQT-Tet: 76%, BQT-three-in-one: 88%) and 82% (BQT-Dox: 66%, BQT-Tet: 77%, BQT-three-in-one: 88%), respectively. By logistic regression, higher eradication rates were associated with compliance (OR = 2.96; 95% CI = 1.01-8.84) and no prior metronidazole use (OR = 1.96; 95% CI = 1.15-3.33); BQT-three-in-one was superior to BQT-Dox (OR = 4.46; 95% CI = 2.51-8.27), and BQT-Tet was marginally superior to BQT-Dox (OR = 1.67; 95% CI = 0.85-3.29).Third-line H pylori eradication with bismuth quadruple treatment (after failure with clarithromycin and levofloxacin) offers acceptable efficacy and safety. Highest efficacy was found in compliant patients and those taking 10-day BQT-three-in-one or 14-day BQT-Tet. Doxycycline seems to be less effective and therefore should not be recommended.

The purpose of the study was to assess whether the occurrence of restenosis is associated with CD45+ platelet count and neutrophil to lymphocyte ratio in patients with type 2 diabetes mellitus (DM) after drug-eluting stent (DES) implantation for stable coronary artery disease (CAD). The study comprised 126 patients, including 55 patients with type 2 DM and stable CAD who underwent elective coronary artery stenting with DES and follow-up angiography within 6 to 12 months. Blood samples were collected from each patient on the morning of the coronary angiography procedure. The variables related to in-stent restenosis were selected by logistic regression analysis. The logistic regression analysis showed that 2 inflammatory factors, CD45+ platelet count (odds ratio [OR] = 4.51, 95% confidence interval [CI]: 1.50-13.50, P = .007) and neutrophil to lymphocyte ratio (OR = 3.09, 95% CI: 1.05-9.10, P = .04), were significantly associated with the risk of in-stent restenosis after stenting with DES in patients with stable CAD and type 2 DM. A receiver operator characteristic curve analysis indicated that the area under the curve was 0.83% (0.05%; P < .001), which showed that the logistic model had good predictive accuracy (based on CD45+ platelet count and neutrophil to lymphocyte ratio) for the risk of in-stent restenosis development in DES in patients with CAD and type 2 DM. Two novel biomarkers of restenosis, CD45+ platelet count and neutrophil to lymphocyte ratio, may be effectively used to predict in-stent restenosis after DES implantation in patients with CAD and type 2 DM.

The breast cancer affects women with high mortality and morbidity worldwide. The risk is highest in the most developed world but also is markedly rising in the developing countries. It is well documented that melatonin has a significant anti-tumor activities demonstrated on various cancer types in a plethora of preclinical studies. In breast cancer, melatonin is capable to disrupt estrogen-dependent cell signaling, resulting in a reduction of estrogen-stimulated cells, moreover, it’s obvious neuro-immunomodulatory effect in organism was described. Several prospective studies have demonstrated the inverse correlation between melatonin metabolites and the risk of breast cancer. This correlation was confirmed by observational studies that found lower melatonin levels in breast cancer patients. Moreover, clinical studies have showed that circadian disruption of melatonin synthesis, specifically night shift work, is linked to increased breast cancer risk. In this regard, proper light/dark exposure with more selective use of light at night along with oral supplementation of melatonin may have benefits for high-risk women. The results of current preclinical studies, the mechanism of action, and clinical efficacy of melatonin in breast cancer are reviewed in this paper. Melatonin alone or in combined administration seems to be appropriate drug for the treatment of early stages of breast cancer with documented low toxicity over a wide range of doses. These and other issues are also discussed.

Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and more than 90% of neoplasms arising from the kidney. Uninformative percutaneous kidney biopsies vary from 10 to 23%. As a result, 7.5–33.6% of partial nephrectomies in patients with small renal masses (SRM) are performed on benign renal tumors. The aim of this study was to assess the feasibility of the apparent diffusion coefficient (ADC) of the diffusion-weighted imaging (DWI) of MRI, as RCC imaging biomarker for differentiation of SRM. Adult patients (n = 158) with 170 SRM were enrolled into this study. The control group were healthy volunteers with normal clinical and radiologic findings (n = 15). All participants underwent MRI with DWI sequence included. Mean ADC values of solid RCC (1.65 ± 0.38 × 10−3 mm2/s) were lower than healthy renal parenchyma (2.47 ± 0.12 × 10−3 mm2/s, p

The objective was to assess aseptic complications and functional outcome using a primary total hip arthroplasty with modular neck. Prospective cohort of 317 consecutive patients. The mean age was 61.1 (range, 41–84) years. The H-Max-M model (Lima, Italy) system was used in all patients. The functional assessment was made by the Harris Hip Score, Short Form-36 (SF-36), Western Ontario and McMaster Universities Osteoarthritis Index and visual analogue scale for pain. Radiological outcomes were also assessed, and adverse events and complications were noted. The mean follow-up was 6.1 (range, 2–8) years. Functional outcome significantly improved in most patients. There were 3 deep infections (0.9%) and 17 aseptic complications (5.3%) including 1 intraoperative acetabular fracture, 3 later periprosthetic femoral fractures, 1 broken ceramic insert, 1 acetabular loosening, 3 femoral loosening and 1 broken titanium modular neck in a obese patient. No pseudotumors or elevated serum levels of metal ions were found among the patients with radiolucent lines or aseptic loosening. The findings in the present study showed that the H-MAX-M stem provided satisfactory functional outcome in most patients with a low rate of complications attributable to the modular neck design. We consider that using this novel modular neck-stem coupling design can be an alternative to the conventional monoblock stems in patients without overweight.

An extensive cross-sectional study to determine the seroprevalence of and associated risk factors for Brucella infection was performed in dairy and mixed (dairy-beef) cattle herds in Ecuador. A total of 2666 serum samples from 386 farms were analyzed using Rose Bengal test and a blocking ELISA test. In addition, a questionnaire with 57 variables related to management, feeding, facilities, biosecurity, and animal health was filled in every cattle farm. A Generalized Estimating Equations model was used to determine the factors associated with Brucella seropositivity. The true prevalence of Brucella seropositivity in dairy and mixed cattle from Ecuador reached 17.0% (CI95% 15.6-18.4%). The herd prevalence was 45.1% (174/386) (CI95% 40.1-50.1%), and the within-herd prevalence ranged from 10 to 100% (mean 38.9%; Q1 14.3%, Q2 26.8%, Q3 52.5%). Seven factors were included in the GEE model for Brucella seropositivity: the nominal variables sex (OR 2.03; CI95% 1.32-3.13), herd type (dairy) (OR 1.79; CI95% 1.11-2.87), closed facilities in the farm (OR 1.80; CI95% 1.19-2.74), and ad libitum feeding (OR: 0.32; CI95%: 0.19-0.54), and the quantitative variables age (OR 1.005; CI95% 1.001-1.009), average slope in the farm (%) (OR 1.013; CI95% 1.002-1.024), and annual abortion rate (OR 1.016; CI95% 1.002-1.031). This study remarks the high spread of Brucella infection in cattle farms from Ecuador. In addition, it reports the risk factors associated to this infection in the predominant extensive system existent in this country.

Patient adherence to screening for hepatocellular carcinoma (HCC) is not well known. Our aims were to analyze the adherence to a surveillance program in a prospective cohort of cirrhotic patients and to examine its association with HCC stage at diagnosis. A total of 770 patients with cirrhosis were examined semiannually by ultrasound and alpha-fetoprotein at a tertiary center. We collected data on 17 variables at baseline. Suboptimal adherence was defined as failure to complete 2 consecutive screening rounds. Over a median follow-up period of 42.0 months (interquartile range: 60.0), 125 patients (16.2%) had suboptimal adherence. Active or previous intravenous drug use [hazard ratio (HR), 5.33; 95% confidence interval (CI), 3.07-9.23], active alcohol consumption (HR, 3.03; 95% CI, 2.03-4.51), absence of liver decompensation before the inclusion in the program (HR, 1.65; 95% CI, 1.07-2.55) and aspartate transaminase/alanine transaminase ratio ≥1.6 (HR, 1.82; 95% CI, 1.23-2.70) were independent predictors of suboptimal adherence. Compared with those with optimal adherence, patients with suboptimal adherence had a more advanced HCC stage at diagnosis (P=0.015), they were less frequently treated with curative intention (P=0.078) and survived less (median: 14.2 mo; IQR: 36.0 vs. 22.7 mo; IQR: 47.4; P=0.160), although these differences were not significant. The adherence to the process of HCC surveillance can be considered as adequate among cirrhotic patients. Active alcohol consumption and a history of intravenous drug use are the strongest predictors of suboptimal adherence. These patients have a more advanced HCC stage at diagnosis and tend to be less frequently treated with curative intention.

One of the most common mechanisms of immune evasion in MSI colorectal cancers (CRCs) is loss of HLA class I expression due to mutations in B2M gene which can become a negative predictor for checkpoint blockade therapy. The aim of this study was the determination of prevalence of B2M somatic mutations in MSI CRC patients and relationship between B2M mutations and lymphocytes infiltration and other clinicopathological features as well as detection of methylation changes in B2M promoter region which can be another mechanism of immune escape. In our study, 37 MSI-H and 5 MSI-L patients were selected for screening of B2M mutational and methylation status. The characterization of patients was based on standard histopathological diagnosis and TNM classification; BRAF, KRAS mutations, tumor-infiltrating lymphocytes and peritumoral lymphoid reaction were also determined. MSI analysis was performed using fragment analysis. B2M mutations were identified by Sanger sequencing, and methylation of CpG islands in promoter region was detected by methylation-specific PCR. Heterozygous mutations in the B2M gene were detected in five MSI-H patients (13.5%), while the mutation c.45_48delTTCT was determined in four patients and mutation c.276delC was found in two patients. One of these five patients was compound heterozygote harboring both mutations. Methylation of the promoter region of the B2M gene was observed in one patient with MSI-H colorectal cancer. Detection of genetic and epigenetic changes in B2M gene could be important in personalized therapy for CRC patients as these changes may be one of the mechanisms of secondary resistance of MSI positive tumors to immunotherapy.

None of the currently investigated molecular markers demonstrated sufficient accuracy in prognostication of the renal cell carcinoma (RCC) oncologic outcomes; thus, none of them has been recommended for the application in the routine clinical practice. The role of miR-15a as a potential prognostic marker for RCC is still not unveiled. The aim of our study was to assess the expression of miR-15a in tumor tissues of the patients with RCC and to evaluate the possibility of its usage as a prognostic molecular biomarker of this disease. The retrospective included 64 adult patients with clear cell RCC (ccRCC) in whom radical or partial nephrectomy was conducted. After deparaffinization of formalin-fixed paraffin-embedded (FFPE) ccRCC specimens, the tissue expression of miR-15a was measured using the reverse transcription and quantitative polymerase chain reaction in the real time. For the reference, the expression of miR-15a was estimated in 15 FFPE tissue specimens of the normal renal parenchyma. Survival analysis involved all cases of non-metastatic RCCs (n = 57). Five-year cancer-specific survival (CSS) was estimated by means of the Kaplan–Meier method and was calculated from the date of surgery to the date of death. Patients with the RCC were characterized by significantly upregulated tumor tissue mean levels of miR-15a compared to the healthy controls: 0.10 ± 2.62 relative units (RU) versus 4.84E − 03 ± 3.11E − 03 RU (p

Hyperglycaemia and type 2 diabetes (T2D) are associated with impaired insulin secretion and/or insulin action. Since few studies have addressed the relation between DNA methylation patterns with elaborated surrogates of insulin secretion/sensitivity based on the intravenous glucose tolerance test (IVGTT), the aim of this study was to evaluate the association between DNA methylation and an insulin sensitivity index based on IVGTT (calculated insulin sensitivity index (CSi)) in peripheral white blood cells from 57 non-diabetic female volunteers. The CSi and acute insulin response (AIR) indexes, as well as the disposition index (DI = CSi × AIR), were estimated from abbreviated IVGTT in 49 apparently healthy Chilean women. Methylation levels were assessed using the Illumina Infinium Human Methylation 450k BeadChip. After a statistical probe filtering, the two top CpGs whose methylation was associated with CSi were cg04615668 and cg07263235, located in the catenin delta 2 (CTNND2) and lipoprotein lipase (LPL) genes, respectively. Both CpGs conjointly predicted insulin sensitivity status with an area under the curve of 0.90. Additionally, cg04615668 correlated with homeostasis model assessment insulin-sensitivity (HOMA-S) and AIR, whereas cg07263235 was associated with plasma creatinine and DI. These results add further insights into the epigenetic regulation of insulin sensitivity and associated complications, pointing the CTNND2 and LPL genes as potential underlying epigenetic biomarkers for future risk of insulin-related diseases.

Background and objective: To assess the usefulness of a risk scale based on serum procalcitonin (PCT) compared to the Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) scale in the early discrimination between necrotising fasciitis (NF) and cellulitis of the extremities. Materials and methods: Retrospective study of consecutive patients with confirmed diagnosis of NF in one limb (n = 11). This study group was compared with 23 consecutive patients with a diagnosis of severe limbs cellulitis during the same period. The clinical data and laboratory parameters were analysed, the main variable was the serum level of PCT upon admission. The capacity for NF diagnosis of the two methods, PCT level and LRINEC scale score, were evaluated by ROC curve and determined by the calculation of the area under the curve (AUC). Results: The AUC was significantly higher with PCT measurement, both as a continuous variable and when the risk was categorised. The cut-off point for the PCT level with the highest AUC under the curve was from 0.87 ng/ml (sensitivity 90.9%, specificity 82.6%), whereas it was a score of 5 on the LRINEC scale (sensitivity 72.7%, specificity 82.6%). Conclusion: PCT measurement was a more effective method than the LRINEC score for early discrimination between NF and cellulitis of the extremities. A low level of PCT, associated with the patient's clinical status and physical examination is especially useful to rule out an early diagnosis of NF. (C) 2019 Elsevier Espafia, S.L.U. All rights reserved.

Most peripheral serotonin (5-hydroxytryptamine (5HT)) is synthetized in the gut with platelets being its main circulating reservoir. 5HT is acting as a hormone in key organs to regulate glucose and lipid metabolism. However, the relation between platelet 5HT levels and traits related to glucose homeostasis and lipid metabolism in humans remains poorly explored. The objectives of this study were (a) to assess the association between platelet 5HT levels and plasma concentration of nonesterified fatty acids (NEFAs) and some adipokines including leptin and its soluble leptin receptor (sOb-R), (b) to assess the association between platelet 5HT levels and anthropometric traits and indexes of insulin secretion/sensitivity derived from oral glucose tolerance test (OGTT), and (c) to evaluate changes in platelet 5HT levels in response to OGTT. In a cross-sectional study, 59 normoglycemic women underwent a standard 2-hour OGTT. Plasma leptin, sOb-R, total and high molecular weight adiponectin, TNFα, and MCP1 were determined by immunoassays. Platelet 5HT levels and NEFAs were measured before and after OGTT. The free leptin index was calculated from leptin and sOb-R measurements. Insulin sensitivity indexes derived from OGTT (HOMA-S and Matsuda ISICOMP) and plasma NEFAs (Adipose-IR, Revised QUICKI) were also calculated. Our data show that among metabolic traits, platelet 5HT levels were associated with plasma sOb-R (r=0.39,p=0.003, correctedp=0.018). Platelet 5HT levels were reduced in response to OGTT (779±237vs.731±217 ng/109platelets,p=0.005). In conclusion, platelet 5HT levels are positively associated with plasma sOb-R concentrations and reduced in response to glucose intake possibly indicating a role of peripheral 5HT in leptin-mediated appetite regulation.

The hitherto unknown larva of Apatania theischingerorum Malicky 1981 is described, based on the association with adult females using sequence data from the mitochondrial cytochrome c oxidase region. Genetic data confirmed the distinct status of this taxon within the parthenogenetic Apatania muliebris complex (Schmid 1954). We provide information on the morphology of the larva and figure the most important diagnostic features. Apatania theischingerorum is morphologically close to A. fimbriata (Pictet 1834). In the context of the Apataniidae key of Waringer et al. (2015), the species pair can be separated by pleural setation patterns on abdominal segment I and by their distribution ranges in Europe: A. fimbriata is known from the Alps, the western and central highlands, the western plains, the Hungarian lowlands and the Carpathians, whereas A. theischingerorum has been recorded exclusively on the Iberian peninsula.

The clinical and prognostic usefulness of tricuspid annular plane systolic excursion (TAPSE) is well established. However, the ability of TAPSE to assess right ventricular (RV) function in patients with previous tricuspid valve annulopasty is controversial. This study examined the TAPSE suitability in patients with previous tricuspid valve annuloplasty using right ventricular fractional area change (RVFAC) as reference method.We retrospectively analyzed 53 patients who underwent tricuspid valve annuloplasty at our hospital between 2013 and 2016. TAPSE and RVFAC were obtained in preoperative and postoperative periods using standard methodology.Mean age was 68±12years and 34 patients (64.1%) were women. TAPSE decreased significantly after surgery in comparison with pre-surgical values (17±4.2 Vs 12.9±4.1mm, p0.001). On the contrary, RVFAC did not change significantly after surgery (37±9.2 Vs 36.2.9, p=0.25). The correlation between RVFAC and TAPSE was better in the preoperative (r=0.63, p0.0001) than in the postoperative period (r=0.38, P=0.005). Good intra- and interobserver agreement for TAPSE and RVFAC was obtained, with intraclass correlation coefficients of 0.97 and 0.92 for TAPSE; and 0.90 and 0.85 for RVFAC, respectively.These findings suggest that TAPSE is not suitable after tricuspid valve annuloplasty and it leads to an underestimation of RV systolic function. It seems to be appropriate to rely on echocardiographic parameters of global RV function such as RVFAC in this context.

Gestational anemia increases the incidence of maternal and fetal complications. Adjuvant recombinant human erythropoietin (rHuEPO) has been used in patients who refuse blood transfusions, have a low response to treatment with iron sulfate, have limited time before birth, or have other illnesses that complicate the anemia. We demonstrated that the use of adjuvant rHuEPO with iron sulfate reduces the anemia time period and is innocuous to the fetus.An experimental longitudinal prospective study; 100 pregnant women in their third trimester were included. Group 1 (n=50) was set as control for prevalence of anemia and establish hematological maternal and fetal parameters at delivery for our population; 50 women diagnosed with iron deficiency anemia were randomly assigned to treatment groups. Group 2 (n=25) third trimester women with a hemoglobin of 11g/dL were treated with iron sulfate, 600mg administered orally daily for 4 weeks, evaluating the hematologic response for the mother weekly and for both mother and fetus at birth; Group 3 (n=25) women similar to group 2, treated in addition with adjuvant rHuEPO, 4000 units subcutaneously, three times a week, for 4 weeks evaluating the same parameters.Group 2 and 3 showed a corrected anemia before delivery (mean 11.1 vs 11.4g/dL), but Group 3 showed a statistically broader and more rapid increase in hemoglobin (1.22 vs 1.92g/dL, p value 0.013) with an rHuEPO dose of 4000 units, three times a week for 1 month. No clinical or hematologic difference or changes in growth were observed in the fetus.Erythropoietin is safe and effective for both mother and fetus, although an ideal pregnancy dose has not yet been established.

Background/Aim Facial injury in adults can commonly result in fractures of the mandible. Autologous mesenchymal stem cells (AMSCs) transplantation is proposed as an alternative to conventional graft treatment to improve bone regeneration. The aim was to evaluate the effectiveness of AMSCs application in mandibular fractures to reduce regeneration time and increase bone quality. Materials and Methods This study was a single blind controlled clinical trial conducted in patients with mandibular angle fractures. Patients were divided into: Study Group fracture reduction plus application of AMSCs, and Control Group only fracture reduction. AMSCs were obtained from adipose tissue 24 hrs before the procedure. Intensity and density were evaluated in normal bone and fractured bone at 4 and 12 weeks after surgery using panoramic radiography and computed tomography. Results A total of 20 patients, 10 in each group were included. The Study Group had a mean age of 31.2 ± 6.3 years and the Control Group mean age was 29.7 ± 7.2 years. All patients were male. Bone quality measured in Gray levels at week 4 was 108.82 ± 3.4 vs 93.92 ± 2.6 (P = 0.000) using panoramic radiography and 123 ± 4.53 vs 99.72 ± 5.72 (P = 0.000) using Computed Tomography. At week 12, the measurements were 153.53±1.83 vs 101.81 ± 4.83 (P = 0.000) using panoramic radiography and 165.4 ± 4.2 vs 112.05 ± 2.1 (P = 0.000) using Tomography in the Study and Control Groups respectively. Conclusion Similar ossification values were obtained after 4 weeks when the use of AMSCs was compared to simple fracture reduction. However, after 12 weeks, the AMSCs group had a 36.48% higher ossification rate. This article is protected by copyright. All rights reserved.

Background:Biomechanical stress and inflammatory biomarkers relate to global contractility dysfunction; however, adding these biomarkers into a risk model constructed on clinical data does not improve its prediction value in chronic heart failure (CHF).Aim:The aim of this study was to evaluate whether biomarkers predict declining of left ventricular global contractility function in diabetic patients with ischemia-induced CHF.Patients and Methods:The study retrospectively evolved 54 diabetic patients who had systolic or diastolic ischemia-induced CHF that was defined as left-ventricular ejection fraction (LVEF) ≤45% or 46-55% respectively assessed by quantitative echocardiography and other conventional criteria according to current clinical guidelines. Two-dimensional transthoracic echocardiography and tissue Doppler imaging were performed according to a conventional method. Radial, longitudinal, and circumferential strain and strain rate values were obtained by speckle-tracking Imaging analysis of both LV short axis and long axis views. Serum adiponectin, NT-pro brain natriuretic peptide (BNP), osteoprotegerin, and hs- C-reactive protein (CRP) were determined at baseline by ELISA.Results:We found lower global longitudinal strain and strain rate in diabetic patients with LVEF Conclusion:We suggest that osteoprotegerin may be useful in improving the NT-proBNP based model as predictor of decreased global contractility function in diabetic patients with CHF.

Impaired baroreflex function is associated with a shift in autonomic balance towards sympathetic dominance, which may play important role in the development of arterial hypertension and consequent target organ damage. To determine the effect of treatment on the cardiovascular autonomic modulation expressed by baroreflex sensitivity (BRS) in hypertensives. A total of one hundred fourteen hypertensive patients (58 male/56 female, 65 ± 13 years of age, BMI 30 ± 3.4 kg/m2) were enrolled. Control group of 20 subjects with normal blood pressure (BP) (ten male/ten female, 59 ± 8 years of age, body mass index 28.3 ± 2.5 kg/m2) without any treatment was also studied. BRS and BRSf were determined by the sequence and spectral method: a 5-min on-invasive beat-to-beat recording of blood pressure and R-R interval with use of Collin CBM-7000 monitor, controlled breathing at a frequency of 0.1 Hz. Significant negative correlation between spontaneous BRS and BP was present in hypertensives (r = −0.52, p

Insulin secretion and insulin sensitivity indexes are related by hyperbolic functions, allowing the calculation of the disposition index (DI) as the product of the acute insulin response (AIR) and the insulin sensitivity index (Si) from intravenous glucose tolerance test (IVGTT). Our objective was to develop an oral-DI based on the oral glucose tolerance test (OGTT) and to assess its association with glucose tolerance status. This research is structured in three studies. Study 1: OGTT were performed in 833 non-diabetic Chilean women (18-60 years) without family history of diabetes mellitus. Study 2: an independent group of n = 57 non-diabetic (18-46 years) without family history of diabetes mellitus carried out an OGTT and an abbreviated IVGTT. Study 3: a sample of 1674 Chilean adults (18-60 years) with different glycaemic status performed an OGTT. An adequate statistical fit for a rectangular hyperbola was found between the area under the curve of insulin-to-glucose ratio (AUCI/G-R) and the Matsuda ISI-COMP index (study 1). The oral-DI derived as AUCI/G-R × ISI-COMP was previously termed insulin-secretion-sensitivity index-2 (ISSI-2). ISSI-2 significantly correlated with DI from IVGTT (rho = 0.34; p = 0.009) (study 2). ISSI-2 shows important differences across groups of subjects with different glycaemic status (study 3). We have confirmed that ISSI-2 replicates the mathematical properties of DI, showing significant correlations with DI from the abbreviated MM-IVGTT. These results indicate that ISSI-2 constitutes a surrogate measure of insulin secretion relative to insulin sensitivity and emphasizes the pivotal role of impaired insulin secretion in the development of glucose homeostasis dysregulation.

Background and Aim Intermediate-risk patients following a colorectal cancer screening program may have differential risk of advanced lesions depending on the findings of an index colonoscopy. The aim of the present study was to comparatively assess advanced colorectal neoplasia risk at the first follow-up colonoscopy among the different intermediate-risk subgroups with a focus on patients with three to four adenomas. Methods All patients recruited for a baseline screening colonoscopy between 2006 and 2011 were included. Number, size and histopathological characteristics of adenomas were collected. Main outcome was an advanced colorectal neoplasia detection rate (invasive carcinoma or advanced adenoma) at the first follow-up colonoscopy. Low- and high-risk patients were excluded. Results Five hundred and sixty-one intermediate-risk patients (63.3% men, mean age: 59.01 ± 6.16 years) underwent indexing and follow-up colonoscopy. By multivariate analysis, three to four adenomas (OR: 3.613 [95% CI: 1.661–7.859], P = 0.001) and adenoma size ≥10

Significance Maintaining low CO2 levels in our bodies is critical for life and depends on neurons that generate the respiratory rhythm and monitor tissue gas levels. Inadequate response to increasing levels of CO2 is common in congenital hypoventilation diseases. Here, we identified a mutation in LBX1, a homeodomain transcription factor, that causes congenital hypoventilation in humans. The mutation alters the C terminus of the protein without disturbing its DNA-binding domain. Mouse models carrying an analogous mutation recapitulate the disease. The mutation spares most Lbx1 functions, but selectively affects development of a small group of neurons central in respiration. Our work reveals a very unusual pathomechanism, a mutation that hampers a small subset of functions carried out by a transcription factor., The respiratory rhythm is generated by the preBötzinger complex in the medulla oblongata, and is modulated by neurons in the retrotrapezoid nucleus (RTN), which are essential for accelerating respiration in response to high CO2. Here we identify a LBX1 frameshift (LBX1FS) mutation in patients with congenital central hypoventilation. The mutation alters the C-terminal but not the DNA-binding domain of LBX1. Mice with the analogous mutation recapitulate the breathing deficits found in humans. Furthermore, the mutation only interferes with a small subset of Lbx1 functions, and in particular with development of RTN neurons that coexpress Lbx1 and Phox2b. Genome-wide analyses in a cell culture model show that Lbx1FS and wild-type Lbx1 proteins are mostly bound to similar sites, but that Lbx1FS is unable to cooperate with Phox2b. Thus, our analyses on Lbx1FS (dys)function reveals an unusual pathomechanism; that is, a mutation that selectively interferes with the ability of Lbx1 to cooperate with Phox2b, and thus impairs the development of a small subpopulation of neurons essential for respiratory control.

Celiac disease (CD) is a genetically conditioned autoimmune process that appears in susceptible people. It can affect people of any age, and slightly predominates in females. It has a fairly homogenous global distribution, with an average prevalence of 1–2%, the frequency having increased in recent decades. The only effective treatment is a strict and permanent gluten-free diet (GFD), although the level of compliance is poor, at about 50% of cases. To monitor the effectiveness of the GFD, several procedures involving various approaches are employed: (a) Periodic visits by expert Nutritionists; (b) Clinical follow-up; (c) Serological time controls of specific antibodies; (d) Serial endoscopies with collection of duodenal biopsies; (e) Use of structured questionnaires; and (f) Determination of gluten peptides derived from gluten in faeces and/or urine. All of these procedures are useful when applied, alone or in combination, depending on the cases. Some patients will only need to consult to their doctors, while others will require a multidisciplinary approach to assess their compliance with the GFD. In children, normalization of duodenal mucosa was achieved in 95% of cases within two years, while it is more delayed in adults, whose mucosa take longer time (3–5 years) to heal completely.

The Gilles de la Tourette syndrome (GTS) and Non-Coeliac Gluten Sensitivity (NCGS) may be associated. We analyse the efficacy of a gluten-free diet (GFD) in 29 patients with GTS (23 children; six adults) in a prospective pilot study. All of them followed a GFD for one year. The Yale Global Tics Severity Scale (YGTSS), the Yale-Brown Obsessive-Compulsive Scale—Self Report (Y-BOCS) or the Children’s Yale-Brown Obsessive-Compulsive Scale—Self Report (CY-BOCS), and the Cavanna’s Quality of Life Questionnaire applied to GTS (GTS-QOL) were compared before and after the GFD; 74% of children and 50% of adults were males, not significant (NS). At the beginning of the study, 69% of children and 100% of adults had associated obsessive-compulsive disorder (OCD) (NS). At baseline, the YGTSS scores were 55.0 ± 17.5 (children) and 55.8 ± 19.8 (adults) (NS), the Y-BOCS/CY-BOCS scores were 15.3, (standard deviation (SD) = 12.3) (children) and 26.8 (9.2) (adults) (p = 0.043), and the GTS-QOL scores were 42.8 ± 18.5 (children) and 64 ± 7.9 (adults) (p = 0.000). NCGS was frequent in both groups, with headaches reported by 47.0% of children and 83.6% of adults (p = 0.001). After one year on a GFD there was a marked reduction in measures of tics (YGTSS) (p = 0.001), and the intensity and frequency of OCD (Y-BOCS/CY-BOCS) (p = 0.001), along with improved generic quality of life (p = 0.001) in children and adults. In conclusion, a GFD maintained for one year in GTS patients led to a marked reduction in tics and OCD both in children and adults.

Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is a mitochondrial-derived peptide that attenuates weight gain and hyperinsulinemia when administered to high fat-fed mice. MOTS-c is therefore a potential regulator of metabolic homeostasis under conditions of high-energy supply. However, the effect of insulin resistance and obesity on plasma MOTS-c concentration in humans is unknown. To gain insight into MOTS-c regulation, we measured plasma MOTS-c concentration and analyzed its relationship with insulin sensitivity surrogates, in lean and obese humans (n=10 per group). Obese individuals had impaired insulin sensitivity as indicated by low Matsuda and high Homeostatic Model Assessment (HOMA) indexes. Although plasma MOTS-c concentration was similar in lean and obese individuals (0.48±0.16 and 0.52±0.15 ng/mL; p=0.60), it was correlated with HOMA (r=0.53; p

Introduction and objectives: Late functional tricuspid regurgitation after rheumatic left-sided valve surgery is an important predictor of poor prognosis. This study investigated the usefulness and accuracy of 3-dimensional transthoracic echocardiography tricuspid area compared with conventional 2-dimensional diameter (2DD) for assessing significant tricuspid annulus dilatation, providing cutoff values that could be used in clinical practice to improve patient selection for surgery. Methods: We prospectively included 109 patients with rheumatic heart disease in the absence of previous valve replacement. Tricuspid regurgitation was divided into 3 groups: mild, moderate, and severe. Optimal 3-dimensional area (3DA) and 2DD cutoff points for identification of significant tricuspid annulus dilatation were obtained and compared with current guideline thresholds. Predictive factors for 3DA dilatation were also assessed. Results: Optimal cutoff points for both absolute and adjusted to body surface area (BSA) tricuspid annulus dilatation were identified (3DA: 10.4 cm2, 6.5 cm2/m2; 2DD: 35 mm, 21 mm/m2); 3DA/BSA had the best diagnostic performance (AUC = 0.83). Three-dimensional transthoracic echocardiography tricuspid area helped to reclassify surgical indication in 14% of patients with mild tricuspid regurgitation (95%CI, 1%-15%; P = .03) and 37% with moderate tricuspid regurgitation (95%CI, 22%-37%; P < .0001), whereas 3DA/BSA changed surgery criteria in cases of mild tricuspid regurgitation (17%; 95%CI, 3%-17%; P = .01) compared with 2DD/BSA. On multivariable analysis, right and left atrial volumes and basal right ventricle diameter were independently correlated with 3DA. Conclusions: The current 40 mm threshold underestimates tricuspid annulus dilatation. Although 21 mm/m2 seems to be a reasonable criterion, the combination with 3DA assessment improves patient selection for surgery. Full English text available from:www.revespcardiol.org/en

BACKGROUND The mucocutaneous clinical profile of patients with amyloidosis in Latin America has been scarcely reported. OBJECTIVE To describe clinical characteristics of skin and mucosal manifestations in systemic amyloidosis in a tertiary care center in Mexico City. METHODS A cross sectional, retrospective analytical study was performed in patients with systemic amyloidosis over a 15-year period. Statistical analysis was done. RESULTS A total of 98 patients were included (53 [54%] men; overall median age = 49 years old). Acquired systemic immunoglobulin light chain amyloidosis (AL) was the most common (49%) type, followed by (24.5%) wild-type transthyretin amyloidosis (H-TTR) (24.5%), undetermined cases (21%), and reactive systemic amyloidosis (AA) (6.1%). There were mucocutaneous manifestations in 34.7% of cases, mostly multiple myeloma-related AL (ALMM). Head and neck was the most often affected site (38.2%), and purpuric macules were the most common morphology (44.1%). Mucocutaneous affectation was predominantly observed in AL (50.0%) compared to other types (20.0%) of amyloidosis (P = 0.01). Likewise, involvement of organs was also significantly different among the diverse amyloidosis types (P

Percutaneous nephrolithotomy is an efficient approach for treatment of different types of kidney stones. Various types of access techniques have been described like sequential dilatation and one-shot procedure.To determine the differences in time of exposure to X-rays and hemoglobin levels between techniques.Controlled clinical trial. Patients older than 18 years with complex/uncomplicated kidney stones, without urine infection were included. They were assigned randomly to one of the two techniques. Response variables were determined before and 24 h after procedures.59 patients were included: 30 underwent one-shot procedure (study-group) and 29 sequential dilatation (control-group). Baseline characteristics were similar. Study group had a lower postoperative hemoglobin decline than control group (0.81 vs. 2.03 g/dl, respectively; p0.001); X-ray exposure time (69.6 vs. 100.62 s; p0.001) and postoperative creatinine serum levels (0.93 ± 0.29 vs. 1.13 ± 0.4 mg/dl; p = 0.039). No significant differences in postoperative morbidity were found.One-shot technique demonstrated better results compared to sequential dilatation.

Background/Aims: To evaluate the association between allelic variants of melanocortin receptors -3 and -4 (MC3R and MC4R, respectively) and leptin receptor (LEPR) genes with body mass index (BMI) and eating behavior. Methods: We selected 344 Chilean adults (57.8% women; age 39.1 ± 6.6 years) with a wide variation in BMI (30.3 ± 6.3 kg/m2). The Three-Factor Eating Questionnaire-R18 that measures uncontrolled eating (UE), emotional eating (EE) and cognitive restraint scores was adapted, validated and assessed for association with BMI. Genotypes were determined by polymerase chain reaction followed by restriction fragment length polymorphism techniques and Taqman assays. Results: Higher EE scores were found in obese vs. non-obese in both men (p = 0.01) and women (p < 0.001). UE scores were significantly associated with BMI only in women (p = 0.002). No significant differences in eating behavior scores or BMI were found by LEPR (rs1137101, rs8179183 and rs1137100 polymorphisms) or MC3R (rs3746619 and rs3827103). Carriers of the C allele for MC4R rs17782313 showed significantly higher scores of UE compared to non-carriers (2.3 ± 0.8 vs. 2.0 ± 0.7; p = 0.02). Additionally, we also report a monogenic case of obesity carrying the pathogenic mutation 449C>T (Thr150Ile) in MC4R gene with no apparent alterations in eating behavior scores. Conclusions: UE scores were higher in C-allele carriers of MC4R-rs17782313 compared to non-carriers.

OBJECTIVE: Subclinical hypothyroidism (SH) is associated with a moderately elevated risk of heart failure events among older adults. The objective of our prospective study was to assess the impact of thyroid hormone replacement therapy (HRT) with low doses of L- thyroxine (6.25-25 µg/day) on left ventricular diastolic function in patients with SH. MATERIALS AND METHODS: 33 patients with SH and 25 healthy controls were involved. All participants underwent standard echocardiography and Doppler imaging at baseline and, the patient group, also after a course of HRT. RESULTS: At baseline, patients with SH showed significantly lower E (0.79 ± 0.22 vs. 0.93 ± 0.19, p < 0.001), E/A ratio (1.19 ± 0.29 vs. 1.31 ± 0.25, p < 0.003), and higher intraventricular septum thickness (IVST) (0.99 ± 0.14 vs. 0.89 ± 0.18, p < 0.001) in comparison with healthy controls. After 6 months of therapy, the E/A ratio underwent significant increase (1.28 ± 0.21 vs. 1.19 ± 0.29, p < 0.001), while the IVS displayed a robust reduction (0.92 ± 0.16 vs. 0.99 ± 0.14, p < 0.001). CONCLUSIONS: HRT with low-dosed L-thyroxine may improve left ventricular diastolic function in patients with SH.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction Chronic hepatitis C (CHC) is a major cause of liver disease worldwide which often leads to progressive liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). CHC displays heterogeneous progression depending on a broad set of factors, some of them intrinsic to each individual such as the patient’s genetic profile. This study aims to evaluate the contribution of certain genetic variants of crucial interferon alpha and lambda signaling pathways to the hepatic necroinflammatory activity (NIA) grade of CHC patients. Methods NIA was evaluated in 119 CHC patients by METAVIR scale and classified as low (NIA = 0–2, n = 80) or high grade (NIA = 3, n = 39). In a candidate gene approach, 64 SNPs located in 30 different genes related to interferon pathways (IL-28B, IFNAR1-2, JAK-STAT and OAS1-3, among others) were genotyped using the Illumina GoldenGate® Genotyping Assay. Statistical association was determined by logistic regression and expressed as OR and 95% CI. Those SNPs significantly associated were further adjusted by other covariates. Results Seven SNPs located in IL-28B (rs12979860), JAK1 (rs11576173 and rs1497056), TYK2 (rs280519), OAS1 (rs2057778), SOCS1 (rs33932899) and RNASEL (rs3738579) genes were significantly related to severe NIA grade (p < 0.05). Regarding to clinical variables, elevated NIA was notably associated with aspartate aminotransferase (AST) serum levels > 40 IU/L (p < 0.05) but not with other clinical factors. Multivariate logistic regression analysis of these factors reflected that AST ( > 40 IU/L), TYK2 rs280519 (G allele) and RNASEL rs3738579 (G allele) were factors independently associated with elevated NIA (p < 0.05). AST concentration showed a moderate AUC value (AUC = 0.63), similar to TYK2 (rs280519) and RNASEL (rs3738579) SNPs (AUC = 0.61, both) in the ROC_AUC analysis. Interestingly, the model including all significant variables reached a considerable predictive value (AUC = 0.74). Conclusion The identified genetic variants in interferon signaling pathways may constitute useful prognostic markers of CHC progression. Further validation in larger cohorts of patients is needed, This work was supported by Ayudas Investigación Oncológica AIO-2010 to PSC ; Ayudas Proyectos de Investigación Fundación Mutua Madrileña 2010 to RMO; Ayudas Proyectos de Ayudas Proyectos de Investigación Fundación Mutua Madrileña 2012 to PSC; Programa Estatal de Investigación Fundamental Ministerio de Economía Industria y Competitividad SAF 2010-21805 to RMO

Surveillance for hepatocellular carcinoma (HCC) intends to detect tumors at an early stage to improve survival. The study aims were to assess the frequency and risk factors associated with HCC surveillance failure.The study analyzed data from 188 consecutive patients diagnosed with HCC within a surveillance program conducted among 1,242 cirrhotic patients and based on ultrasonography and alpha-fetoprotein (AFP) testing every 3 or 6 months. Program failure was defined as the detection of HCC exceeding the Milan criteria. Variables recorded at entry into the program, during follow-up and at HCC diagnosis, were analyzed.At diagnosis, 50 (26.6%) HCC tumors were beyond the Milan criteria. In univariate analysis, Child-Pugh B at entry (P = 0.03), development of complications of portal hypertension before tumor diagnosis (P = 0.03), and failure to complete the prior screening round (P = 0.02), Child-Pugh B/C (P = 0.001) and AFP ≥ 100 ng/mL (P = 0.03) at diagnosis, were associated with failure. In multivariate analysis, only Child-Pugh B/C (hazard ratio, 3.18; 95% confidence interval, 1.66-6.10, P 0.001) and AFP ≥ 100 ng/mL, both at diagnosis (hazard ratio, 2.80; 95% confidence interval, 1.37-5.71, P = 0.005), were independently associated with failure. Survival was higher among patients with tumors within the Milan criteria than those with program failure (33.9 vs 7.6 months, P 0.001).Approximately 25% of HCC cases diagnosed among patients included in a surveillance program were beyond the Milan criteria. Child-Pugh B/C and AFP ≥ 100 ng/mL at diagnosis were associated with program failure. However, Child-Pugh B at entry and development of liver-related complications during follow-up can be early predictors of failure.

The blood concentrations of total cholesterol and low-density lipoprotein (LDL) do not predict survival in patients older than 60 years. The atherogenic index of plasma (AIP) is a logarithm of the triacylglycerol to high-density lipoprotein (HDL) ratio and a surrogate for the concentration of small dense LDL. It might be a better reflection of the risk of all-cause death in elderly patients. We conducted a prospective observational study of patients with arterial hypertension older than 60 years. The concentrations of total cholesterol, LDL, HDL and triacylglycerol were measured at the time of the recruitment and the patients were observed for 10 years. Cox regression analysis was performed to assess the effects of lipoproteins and AIP on survival. A total of 500 patients were recruited and 473 of them (226 men, 247 women) either died or successfully completed the 10-year follow-up and were included in the analysis. The AIP was positively associated, while HDL concentration was negatively associated with the risk of all-cause death adjusted for age, smoking habits, statin use, history of diabetes mellitus, myocardial infarction, stroke and peripheral artery occlusive disease (PAOD) in elderly women but not in men. The LDL, total cholesterol, triacylglycerol and non-HDL concentrations were not associated with the risk of death in both sexes. The AIP is positively associated with the risk of all-cause death in elderly women with arterial hypertension independent of age, smoking habits, statin therapy and comorbidities.

This study aimed at investigating the associations between inflammatory mediators, symptoms and psychological disturbances in inflammatory bowel disease (IBD) patients.IBD patients and patient controls were examined during a single visit to a gastroenterology clinic. Disease activity was assessed using the Mayo index for ulcerative colitis (UC), inflammatory bowel disease questionnaire (IBDQ), Crohn's disease activity index (CDAI) and Crohn's disease endoscopic index of severity (CDEIS). Gene expression of inflammatory mediators were measured in intestinal biopsies and whole blood samples along with circulating concentrations of interleukin (IL)-6, interferon (IFN)γ, C-reactive protein (CRP), kynurenine and tryptophan. Validated depression, anxiety and quality of life scores were used to assess psychological well-being.Patients who were symptomatic had the highest depression and anxiety scores, together with increased intestinal expression of IL-1β, IL-6 and matrix metalloproteinase-9, increased circulating IL-6 and CRP, and an increased circulating kynurenine:tryptophan ratio. Increased Hamilton depression (HAM-D) scores in IBD patients were observed independent of the psychological impact of acute symptoms.Active IBD is associated with symptoms of depression and anxiety and with a raised circulating inflammatory mediator profile. Patients with active IBD exhibiting psychological symptoms should undergo psychological evaluation to ensure the psychological aspects of the condition are considered and addressed.

Plasma leptin/adiponectin ratio (LAR) is negatively associated with insulin sensitivity indexes. High-molecular-weight adiponectin (HMWA) was proposed as the most biologically active form of this insulin-sensitizing adipokine. There are no studies assessing the relative merits of leptin/HMWA ratio over LAR as a biomarker of systemic insulin sensitivity. A standard 2-hour oral glucose tolerance test (OGTT; 75 g of glucose) and a short minimal-model intravenous glucose tolerance test (IVGTT; 0.3 g/kg body weight) were performed in 58 Chilean normoglycemic women (age: 27 ± 6.3 years, BMI 23.6 ± 3.2 kg/m2). LAR was negatively associated with HOMA-S (r=−0.49; p<0.0001), Matsuda-ISICOMP (r=−0.54; p<0.0001), and the calculated sensitivity index (CSi) derived from IVGTT (r=−0.38; p=0.007). In comparison to LAR, leptin/HMWA ratio did not increase neither the linear fit (r2) nor the magnitude of association with insulin sensitivity indexes (slope of multiple linear regression). The discriminatory capacity of both ratios to classify insulin-resistant versus insulin-sensitive subjects was similar for HOMA-S (p=0.84), Matsuda-ISICOMP (p=0.43), or CSi (p=0.50). In conclusion, LAR showed consistent negative associations with different systemic insulin sensitivity indexes. The use of HMWA to generate leptin/HMWA ratio did not show any advantage over LAR as a biomarker of systemic insulin sensitivity in normoglycemic women.

Background and Aim There are few data concerning emergency double-balloon enteroscopy (DBE) and its usefulness in the management of severe acute obscure gastrointestinal bleeding (OGIB). The aim of this retrospective study was to evaluate emergency DBE and capsule endoscopy (CE) in patients with overt OGIB, analyzing the feasibility of this combined approach. Methods Emergency DBE in patients with overt OGIB was defined as performance within 24 h of symptom onset. We reported 27 patients (16 men, mean age: 64.6 ± 17.9 years) with overt severe bleeding who underwent 29 emergency DBE (22 anterograde, 7 retrograde). Of 27 patients, 16 (59.3%) underwent CE with real time (RT) viewing. Results Patients were diagnosed with the following: Dieulafoy's lesion (DL; n = 11, 40.7%), angioectasia (n = 7, 25.9%), tumors (n = 4, 14.8%), diverticulum (n = 3, 11.1%), ulcers (n = 2, 7.4%). We diagnosed 23 lesions amenable to endoscopic hemostasis and successfully treated 21 of them (77.8%). DL detection rate was statistically higher in the emergency DBE group than in OGIB patients with DBE done 24 h after symptom onset (40.7% vs 0.9%, respectively, P

The two-dimensional (2D) proximal isovelocity surface area (PISA) method has important technical limitations for mitral valve orifice area (MVA) assessment in mitral stenosis (MS), mainly the geometric assumptions of PISA shape and the requirement of an angle correction factor. Single-beat real-time three-dimensional (3D) color Doppler imaging allows the direct measurement of PISA without geometric assumptions or the requirement of an angle correction factor. The aim of this study was to validate this method in patients with rheumatic MS.Sixty-three consecutive patients with rheumatic MS were included. MVA was assessed using the transthoracic 2D and 3D PISA methods. Planimetry of MVA (2D and 3D) and the pressure half-time method were used as reference methods.The 3D PISA method had better correlations with the reference methods (with 2D planimetry, r = 0.85, P.001; with 3D planimetry, r = 0.89, P.001; and with pressure half-time, r = 0.85, P.001) than the conventional 2D PISA method (with 2D planimetry, r = 0.63, P.001; with 3D planimetry, r = 0.66, P.001; and with pressure half-time, r = 0.68, P.001). In addition, a consistent significant underestimation of MVA using the conventional 2D PISA method was observed. A high percentage (30%) of patients with nonsevere MS by 3D planimetry were misclassified by the 2D PISA method as having severe MS (effective regurgitant orifice area1 cm(2)). In contrast, the 3D PISA method had 94% agreement with 3D planimetry. Good intra- and interobserver agreement for 3D PISA measurements were observed, with intraclass correlation coefficients of 0.95 and 0.90, respectively.MVA assessment using PISA by single-beat real-time 3D color Doppler echocardiography is feasible in the clinical setting and more accurate than the conventional 2D PISA method.

Epidemiological studies demonstrate a link between gastrointestinal cancers and environmental factors such as diet. It has been suggested that environmental cancer risk is determined by the interaction between diet and microbes. Thus, the purpose of this study was to examine the hypothesis that microbiota composition during colorectal cancer (CRC) progression might differ depending on the stage of the disease. A total of 28 age-matched and sex-matched subjects, seven with CRC adenocarcinoma, 11 with tubular adenomas and ten healthy subjects with intact colon, were included into the study. Microbiomes from mucosal and fecal samples were analyzed with 16S ribosomal RNA gene pyrosequencing, together with quantitative PCR of specific bacteria and archaea. The principal coordinates analysis clearly separated healthy tissue samples from polyps and tumors, supporting the presence of specific bacterial consortia that are associated with affected sites and that can serve as potential biomarkers of CRC progression. A higher presence of Fusobacterium nucleatum and Enterobacteriaceae was found by qPCR in samples from CRC compared to healthy controls. We observed a correlation between CRC process development and levels of Methanobacteriales (R = 0.537, P = 0.007) and Methanobrevibacterium (R = 0.574, P = 0.03) in fecal samples. Differences in microbial and archaeal composition between mucosal samples from healthy and disease tissues were observed in tubular adenoma and adenocarcinoma. In addition, microbiota from mucosal samples represented the underlying dysbiosis, whereas fecal samples seem not to be appropriate to detect shifts in microbial composition. CRC risk is influenced by microbial composition, showing differences according to disease progression step and tumor severity.

BACKGROUND Factors associated with performance of interferon-γ release assays (IGRA) and the tuberculin skin test (TST) in screening for latent tuberculosis infection in patients with inflammatory bowel diseases (IBD) are still poorly understood. The influence of peripheral T-cell subset counts on the results also remain unclear. METHODS Prospective single-center study in 205 patients with IBD. Latent tuberculosis infection screening included a chest radiograph, TST (retest if negative), and 2 IGRAs: QuantiFERON-TB Gold In-Tube (QFT-GIT) and TSPOT-TB (TSPOT). T-cell subpopulations were determined by flow cytometry. RESULTS Twenty-one (10.2%) patients had an abnormal chest radiograph, 55 (26.8%) had a positive TST, 16 (7.8%) had a positive QFT-GIT, and 25 (12.6%) had a positive TSPOT. TST positivity was lower in patients on ≥2 immunosuppressants compared with the controls (5-aminosalicylic acid treatment) (10.4% versus 38.2%, respectively) (P = 0.0057). No other drugs influenced TST or IGRA positivity. In patients on corticosteroid treatment, anti-TNF treatment, or ≥2 immunosuppressants, IGRAs detected 10 cases of latent tuberculosis infection not identified by TST. TSPOT and QFT-GIT increased yield by 56% and 22%, respectively. No significant differences in T-cell subpopulations were found between patients with positive or negative TST or TSPOT results. However, patients with positive QFT-GIT findings had more CD8 T cells (mean, 883 ± 576 versus 484 ± 385 cells per microliter in patients with negative results) (P = 0.022). CONCLUSIONS IGRAs can improve TST-based screening in patients with IBD on immunosuppressive therapy. A low CD8 count can affect QFT-GIT results. We suggest combining TSPOT and TST screening in patients with IBD on immunosuppressants.

Background:Presence of macro- and microvascular complications in patients with diabetes mellitus (DM) is not only related to chronic hyperglycemia represented by glycated hemoglobin (HbA1c) but also to acute glycemic fluctuations (glycemic variability, GV). The association between GV and DM complications is not completely clear. Aim of our study was to evaluate GV by MAGE index in patients with type 2 DM and to verify association of MAGE index with presence of macro- and microvascular DM complications.Methods:99 patients with type 2 DM were included in the study. Every patient had done big glycemic profile, from which MAGE index was calculated. Anthropometric measurements, evaluation of HbA1c and fasting plasma glucose (FPG) and assessment for macrovascular (coronary artery disease – CAD; peripheral artery disease – PAD; cerebral stroke – CS) and microvascular (diabetic retinopathy – DR; nephropathy – DN; peripheral neuropathy – DPPN) DM complications were done.Results:Average MAGE index value was 5.15 ± 2.88 mmol/l. We found no significant differences in MAGE index values in subgroups according to presence of neither CAD, CS, PAD nor DR, DN, DPPN. MAGE index value significantly positively correlated with FPG (p < 0.01) and HbA1c (p < 0.001) and negatively with weight (p < 0.05).Conclusion:In our study we failed to show association of MAGE index with presence of macrovascular and microvascular complications in patients with type 2 DM. However, this negative result does not necessarily disprove importance of glycemic variability in pathogenesis of diabetic complications.

BACKGROUND The incidence of hepatitis delta virus (HDV) infection has decreased during the last decades. However, an increasing trend has been reported recently. PATIENTS AND METHODS We carried out a case-control study to analyze changes in its prevalence in 1215 chronic hepatitis B virus (HBV) patients, diagnosed consecutively in a tertiary center, between 1983 and 2012. According to the year of diagnosis, patients were distributed into two groups: A [1983-1997 (n=786)] and B [1998-2012 (n=429)]. RESULTS The prevalence of anti-HDV was 8.2% (9.4% in group A and 6.1% in group B) (P=0.04). Multivariate regression revealed that intravenous drug use [odds ratio (OR) 261.0; 95% confidence interval (CI), 28.7-2368.5; P

Introduction: celiac disease is a chronic condition that requires continued treatment, with the resultant impact on health-related quality of life (HRQOL) of people who suffer it. Most studies in this field have used generic questionnaires to measure HRQOL in celiac patients. It was therefore decided to conduct a study to translate into Spanish and validate a specific questionnaire for celiac disease, the Celiac Disease Quality Of Life Survey (CD-QOL). Objectives: to translate and validate in Spanish the specific celiac disease questionnaire CD-QOL. Methods: a multicenter, prospective, observational study was designed consisting of two phases: In the first phase, the questionnaire was translated and adapted into Spanish using the translation/back translation procedure and an understandability study. In the second phase, internal consistency of the translated questionnaire was analyzed. For this, results of the CD-QOL were compared to those of EuroQol and the Daily Fatigue Impact Scale (D-FIS). Understandability of the translated and adapted questionnaire was tested in six patients, and the validation study was done in 298 celiac patients (201 treated with a gluten-free diet and 97 at diagnosis). Results: in both celiac groups, Cronbach's alpha coefficient was high (0.90), feasibility was excellent (99.2 % of patients completed all questions), and there were no ceiling and floor effects. Spearman correlation to EuroQol and D-FIS was statistically significant (p < 0.05). CD-QOL score was different depending on whether state of health was good, fair, or poor based on the EuroQol score. Conclusion: the Spanish version of the CD-QOL is a valid tool for measuring HRQOL in celiac patients.

Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin fails in >20 % of cases. A rescue therapy with PPI–amoxicillin–levofloxacin still fails in >20 % of patients. To evaluate the efficacy and tolerability of a bismuth-containing quadruple regimen in patients with two consecutive eradication failures. Prospective multicenter study of patients in whom 1st treatment with PPI–clarithromycin–amoxicillin and 2nd with PPI–amoxicillin–levofloxacin had failed. A 3rd eradication regimen with a 7- to 14-day PPI (standard dose b.i.d.), bismuth subcitrate (120 mg q.i.d. or 240 mg b.i.d.), tetracycline (from 250 mg t.i.d. to 500 mg q.i.d.) and metronidazole (from 250 mg t.i.d. to 500 mg q.i.d.). Eradication was confirmed by 13C-urea-breath-test 4–8 weeks after therapy. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by means of a questionnaire. Two hundred patients (mean age 50 years, 55 % females, 20 % peptic ulcer/80 % uninvestigated-functional dyspepsia) were initially included, and two were lost to follow-up. In all, 97 % of patients complied with the protocol. Per-protocol and intention-to-treat eradication rates were 67 % (95 % CI 60–74 %) and 65 % (58–72 %). Adverse effects were reported in 22 % of patients, the most common being nausea (12 %), abdominal pain (11 %), metallic taste (8.5 %), and diarrhea (8 %), none of them severe. A bismuth-containing quadruple regimen is an acceptable third-line strategy and a safe alternative after two previous H. pylori eradication failures with standard clarithromycin- and levofloxacin-containing triple therapies.

Background There is ongoing debate about whether a computed tomography coronary angiography (CTCA) should be aborted when the calcium score (CS) exceeds a certain threshold in patients with chest pain. The aim of this study was to discover whether specific "cutpoints" regarding coronary artery CS could be determined to predict severe coronary stenoses assessed by CTCA, thus identifying patients amenable to an invasive diagnostic approach. Methods 294 consecutive patients with chest pain of uncertain cause who were referred for non-invasive diagnostic CTCA were included. Subjects underwent Agatston CS and CTCA using current 64-slice technology. Results Severe coronary stenoses were noted in 75 of 294 (25.1%) patients on CTCA. A very high prevalence of severe coronary stenoses was found in patients with CS ≥400 (87.0%). The CS had area under the ROC curve 0.86 to predict severe coronary stenoses on CTCA. The best discriminant cut-off point was CS ≥400 (sensitivity of 55.3%, specificity of 93.5, positive predictive value of 85.8%, negative predictive value of 84.0%). Multivariable logistic regression analysis controlling for traditional risk factors showed CS ≥400 remained an independent predictor of severe coronary stenoses on CTCA (OR 14.553, 95% confidence interval 4.043 to 52.384, p Conclusions CS can be used as a "gatekeeper" to CTCA in patients with chest pain. Due to the very high prevalence of severe coronary stenoses in patients with CS ≥400, further evaluation with CTCA is not warranted as these patients should be referred to invasive coronary angiography, avoiding the repeated exposure to ionizing radiation and iodinated contrast.

Background The two-dimensional (2D) proximal isovelocity surface area (PISA) method has known technical limitations, mainly the geometric assumptions of PISA shape required to calculate effective regurgitant orifice area (EROA). Recently developed single-beat real-time three-dimensional (3D) color Doppler imaging allows the direct measurement of PISA without geometric assumptions and has already been validated for mitral regurgitation assessment. The aim of this study was to apply this novel method in patients with chronic tricuspid regurgitation (TR). Methods Ninety patients with chronic TR were enrolled. EROA and regurgitant volume (Rvol) were assessed using transthoracic 2D and 3D PISA methods. Quantitative Doppler and 3D transthoracic planimetry of EROA were used as reference methods. Results Both EROA and Rvol assessed using the 3D PISA method had better correlations with the reference methods than using conventional 2D PISA, particularly in the assessment of eccentric jets. On the basis of 3D planimetry–derived EROA, 35 patients had severe TR (EROA ≥ 0.4 cm 2 ). Among these 35 patients, 25.7% ( n = 9) were underestimated as having nonsevere TR (EROA ≤ 0.4 cm 2 ) using the 2D PISA method. In contrast, the 3D PISA method had 94.3% agreement (33 of 35) with 3D planimetry in classifying severe TR. Good intraobserver and interobserver agreement for 3D PISA measurements was observed, with intraclass correlation coefficients of 0.92 and 0.88 respectively. Conclusions TR quantification using PISA by single-beat real-time 3D color Doppler echocardiography is feasible in the clinical setting and more accurate than the conventional 2D PISA method.