The Use of a PEG/Ascorbate Booster Following Standard Bowel Preparation Improves Visualization for Capsule Endoscopy in a Randomized, Controlled Study

Background/aims: The increasing use of capsule endoscopy (CE) to examine the gastrointestinal tract highlights the need to establish intestinal preparations that ensure optimal visualization while maximizing patient adherence. Thus, we assessed whether bowel preparation involving dietary restriction and a booster regimen produces adequate CE visualization in a real-world clinical setting. Methods: We conducted a randomized, double-blind, prospective study of CE procedures at 2 tertiary-care centers. Patients were allocated to 3 groups: group 1 followed a clear liquid diet and fasting-based bowel preparation for the exploration (n = 55); group 2 followed the same procedure as group 1 and then ingested 1 L of a polyethylene glycol (PEG)/ascorbic acid booster solution when the capsule reached the small intestine (n = 55); and group 3 followed the same procedure but ingesting only 0.5 L of the booster solution (n = 56). The quality of visualization and the average gastric, orocecal and small-bowel transit times were evaluated. Results: A total of 166 patients participated in the study. Significantly higher quality of visualization (Park score) was obtained in group 3 (2.28 ± 0.59) than in group 1 (1.84 ± 0.54, P < .001), while there were no significant differences in the average gastric (range: 36.58- 48.32 min, P = .277), orocecal (range: 322.58-289.45 min, P = .072), and small-bowel transit time (range: 280.71-249.95 min, P = .286) between the 3 groups. Conclusions: Following a clear liquid diet and fasting-based bowel preparation for CE exploration, administering a booster solution of PEG/ascorbic acid after the capsule had reached the small intestine improves mucosal visualization and cleansing without affecting capsule transit times.info:eu-repo/semantics/publishedVersio

Coronary artery bypass surgery in young adults: excellent perioperative results and long-term survival

OBJECTIVES: To analyse perioperative results, long-term survival and freedom from complications after coronary artery bypass grafting (CABG) in young adults. METHODS: A total of 163 patients, 40 years old or younger, had isolated CABG from January 1989 to December 2010. Pre- and perioperative demographic and clinical data were retrieved from a prospectively organised database. Follow-up data were obtained by letter or telephone interviews. The mean age of the patients was 37.6 ± 2.9 years and 146 were men (90%). Fifty-three patients (32.5%) had angina class III/IV; 106 (65.0%), previous myocardial infarction; and 23 (14.1%), impaired left ventricular function (ejection fraction <40%). Indication for surgery was 3-vessel disease in 101 cases (62.0%), 2-vessel disease in 30 (18.4%) and single-vessel disease in 32 (19.6%). The left main stem was affected in 16 patients (9.8%). The mean EuroSCORE II was 0.92 ± 0.71. A total of 417 grafts were constructed (mean 2.6 grafts/patient), 247 of which (59.2%) were arterial. RESULTS: There were no in-hospital deaths. The mean hospital stay was 7.1 ± 4.0 days. Four patients (2.5%) were lost to follow-up, which extended from 3 to 25 years (mean 15.1 ± 5.5 years). There were 22 late deaths, 72.7% of cardiac or unknown origin. The 5-, 10- and 20-year survival rates were 98.7 ± 10.9, 95.2 ± 1.8 and 79.4 ± 4.4%, respectively. Twenty-six patients (18.1%) had non-fatal cardiac adverse complications (myocardial infarct, percutaneous re-revascularization or class III/IV angina), for 5-, 10- and 20-year freedom from complications of 97.9 ± 1.2, 91.9 ± 2.5 and 65.7 ± 7.1%, respectively. Twenty-two patients (17.5%) needed re-revascularization, for 5-, 10- and 20-year freedom from re-revascularization of 97.6 ± 1.4, 91.9 ± 2.6 and 69.5 ± 6.7%, respectively. CONCLUSIONS: Despite the aggressive nature of coronary artery disease in young patients, perioperative death and morbidity rates are low, with good long-term survival and low rates of re-revascularization.info:eu-repo/semantics/publishedVersio

Diabetes as an outcome predictor after heart transplantation

We aimed to compare post-transplantation morbidity and survival among heart transplant recipients with and without diabetes mellitus. A retrospective review of 141 adult patients submitted to heart transplantation from November 2003 to June 2009 (with a minimum follow-up of one year) was undertaken. The patients were divided into two groups: those with (29%) and those without (71%) pre-transplantation diabetes. Those with diabetes were older (57.6±6.1 vs. 52.3±11.1 years; P=0.020) and had lower creatinine clearance (53.6±15.1 vs. 63.7±22.1; P=0.029). Nine patients died in hospital (6.4%; P=non-significant). No significant differences in lipid profiles (diabetes vs. no diabetes) existed before transplantation or at one year afterwards. Patients with diabetes showed a significant deterioration in their one-year lipid profile (158±43 vs.192±38 mg/dL; P=0.001), although one-year fasting diabetic was lower than before (178±80 vs. 138±45 mg/dL; P=0.016). During the first year, 17 (17%) patients previously free of diabetes developed new-onset diabetes. No significant differences were seen in rejection at one year (14% vs. 20%), infection (31% vs. 33%), new-onset renal dysfunction (8% vs. 14%) or mortality (17% vs. 7%). One-year survival was not significantly different (83% vs. 94%), but there was a significant decrease in the survival of individuals with diabetes at three years (73% vs. 91%; P=0.020). No significant difference was found in one-year survival or in terms of higher morbidity in the heart transplant patients with diabetes, but a longer follow-up showed a significant decrease in survival. Nonetheless, the patients with diabetes benefited significantly from transplantation and should not be excluded from it

Complications of endomyocardial biopsy in heart transplant patients: a retrospective study of 2117 consecutive procedures

BACKGROUND: Endomyocardial biopsy (EMB) remains the gold standard for the diagnosis of graft rejection after heart transplantation (HT). Our purpose was to evaluate the rate of complications of this invasive procedure. METHODS: This was a retrospective study of 175 patients, who were transplanted between November 2003 and October 2010 and survived more than 1 month after surgery. We evaluated the number of inconclusive EMB and described the incidence, nature, and subsequent management of several complications associated with this procedure. RESULTS: Over a period of approximately 7 years, we performed 2217 EMB yielding 4972 specimens, namely, an average of 2.3 fragments per procedure. The majority of EMBs (95.3%) were performed by the femoral approach. Only 12 EMB (0.57%) were inconclusive. The overall complication rate was 0.71%. During puncture, one patient experienced a vasovagal reaction and another one, a femoral artery false aneurysm. During the biopsy, there was one case of cardiac perforation with tamponade, two cases of supraventricular tachycardia, and three atrioventricular conduction abnormalities. In 19 patients, histological analysis revealed chordal tissue, but only two patients developed mild tricuspid regurgitation. We observed five cases of coronary artery fistulae. The clinical outcomes were favorable in all cases. CONCLUSION: EMB proved to be a suitable, safe method to monitor rejection after HT

Abordagem Clínica e Terapêutica de Doentes Internados por COVID-19: Uma Coorte Pediátrica em Portugal

Introduction: Coronavirus disease 2019, or COVID-19, in children is usually a mild disease, but severe illness has been reported. Currently, the therapy benefits of antiviral experimental drugs are still uncertain. The main aim of this study is to describe the experience of a level III hospital regarding therapeutic management of hospitalized children with COVID-19 and to characterize clinical features and evolution. Material and methods: This is a descriptive study of patients with COVID-19 in a level III pediatric hospital in Portugal between March and June 2020. Experimental drugs were administered according to the best scientific evidence at the time as 'off-label use'. Results: Among 200 children with SARS-CoV-2 infection, 37 were admitted due to COVID-19. Median age was one year (23 days - 18 years), 43% had comorbidities and 20/37 (54%) received antiviral therapy. Hydroxychloroquine was administered in 13 patients, in monotherapy or combined with lopinavir/ritonavir or azithromycin. Lopinavir/ritonavir was administered in eight patients and three children were treated with remdesivir. The patients who were treated had pneumonia (14), multisystem inflammatory syndrome in children (2), sepsis (2), myocarditis (1), acute respiratory distress syndrome (1), and mild illness with comorbidities (3). Other therapies included methylprednisolone and immunoglobulin (3), enoxaparin (2), antibiotics (16), oxygen (7), corticosteroids, and other inhaled therapy (16). Discussion: Several treatment approaches have been proposed for severe COVID-19, even though none of them had been proven effective or approved for small children. Currently, remdesivir is approved for children aged above 12 years-old. Although 54% of our patients were treated with antivirals, it is important to understand that the favorable clinical evolution could be related with the natural course of the disease. Conclusion: A significant proportion of our population presented severe and critical disease, was hospitalized and received treatment according to the most recent data, although most patients had mild disease. COVID-19 treatment in children is a clinical challenge and clinical trials are urgently needed.info:eu-repo/semantics/publishedVersio

Seroepidemiological survey of transmissible infectious diseases in a portuguese prison establishment

A cross-sectional study was conducted in 151 (71.6%) of 211 male inmates of a regional Portuguese prison in order to establish the seroprevalence for viral hepatitis (HAV, HBV, HCV), human immunodeficiency virus (HIV), syphilis and herpes simplex virus (HSV-1 and HSV-2) and to analyze some psychosocial and criminal characteristics. Mean age was 34 years. Anti-HAV was positive in 69.5% (n = 105) and in 34.4% (n = 52) for anti-HCV. One (0.7%) person had HBsAg and 29 (19.2%) had laboratory markers of past HBV infection. Non-immune inmates for HBV were 40.4% (n = 61). Syphilis was diagnosed in 6.0% (n = 9). The rate of HIV infection was 6.6% (n = 10; all HIV-1). The seropositivity of HSV-2 was 19.9% (n = 30) and of HSV-1 was 82.1% (n = 124). Alcohol dependence was reported by 26.5% (n = 40). Excluding tobacco and prescription medication, 73.5% (n = 111) reported drug use in prison. The most commonly used drugs were: cannabis (100%; n = 111) followed by heroin (56.7%; n = 63). Anti-HCV rate was noteworthy. The HIV infection rate (6.6%) in this regional prison is at least 13 to 22 times greater than in general population. As the inmate return to the community increases the risk of disease exposure for the general population, early detection and counseling is urgently needed for prisoners

Peripheral Attentional Targets under Covert Attention Lead to Paradoxically Enhanced Alpha Desynchronization in Neurofibromatosis Type 1

The limited capacity of the human brain to process the full extent of visual information reaching the visual cortex requires the recruitment of mechanisms of information selection through attention. Neurofibromatosis type-1 (NF1) is a neurodevelopmental disease often exhibiting attentional deficits and learning disabilities, and is considered to model similar impairments common in other neurodevelopmental disorders such as autism. In a previous study, we found that patients with NF1 are more prone to miss targets under overt attention conditions. This finding was interpreted as a result of increased occipito-parietal alpha oscillations. In the present study, we used electroencephalography (EEG) to study alpha power modulations and the performance of patients with NF1 in a covert attention task. Covert attention was required in order to perceive changes (target offset) of a peripherally presented stimulus. Interestingly, alpha oscillations were found to undergo greater desynchronization under this task in the NF1 group compared with control subjects. A similar pattern of desynchronization was found for beta frequencies while no changes in gamma oscillations could be identified. These results are consistent with the notion that different attentional states and task demands generate different patterns of abnormal modulation of alpha oscillatory processes in NF1. Under covert attention conditions and while target offset was reported with relatively high accuracy (over 90% correct responses), excessive desynchronization was found. These findings suggest an abnormal modulation of oscillatory activity and attentional processes in NF1. Given the known role of alpha in modulating attention, we suggest that alpha patterns can show both abnormal increases and decreases that are task and performance dependent, in a way that enhanced alpha desynchronization may reflect a compensatory mechanism to keep performance at normal levels. These results suggest that dysregulation of alpha oscillations may occur in NF1 both in terms of excessive or diminished activation patterns

Curcumin: A multi-Target disease-modifying agent for late-stage transthyretin amyloidosis

Transthyretin amyloidoses encompass a variety of acquired and hereditary diseases triggered by systemic extracellular accumulation of toxic transthyretinaggregates and fibrils, particularly in the peripheral nervous system. Since transthyretin amyloidoses are typically complex progressive disorders, therapeutic approaches aiming multiple molecular targets simultaneously, might improve therapy efficacy and treatment outcome. In this study, we evaluate the protective effect of physiologically achievable doses of curcumin on the cytotoxicity induced by transthyretin oligomers in vitro by showing reduction of caspase-3 activity and the levels of endoplasmic reticulum-resident chaperone binding immunoglobulin protein. When given to an aged Familial Amyloidotic Polyneuropathy mouse model, curcumin not only reduced transthyretin aggregates deposition and toxicity in both gastrointestinal tract and dorsal root ganglia but also remodeled congophilic amyloid material in tissues. In addition, curcumin enhanced internalization, intracellular transport and degradation of transthyretinoligomers by primary macrophages from aged Familial Amyloidotic Polyneuropathy transgenic mice, suggesting an impaired activation of naive phagocytic cells exposed to transthyretin toxic intermediate species. Overall, our results clearly support curcumin or optimized derivatives as promising multi-targetdisease-modifying agent for late-stage transthyretin amyloidosis

Synthesis and structural analysis of the N-terminal domain of the thyroid hormone-binding protein transthyretin

Transthyretin (TTR) is a 55 kDa protein responsible for the transport of thyroid hormones and retinol in human serum. Misfolded forms of the protein are implicated in the amyloid diseases familial amyloidotic polyneuropathy and senile systemic amyloidosis. Its folding properties and stabilization by ligands are of current interest due to their importance in understanding and combating these diseases. To assist in such studies we developed a method for the solid phase synthesis of the monomeric unit of a TTR analogue and its folding to form a functional 55 kDa tetramer. The monomeric unit of the protein was chemically synthesized in three parts, comprising amino acid residues 151, 5499 and 102127, and ligated using chemoselective thioether ligation chemistry. The synthetic protein was folded and assembled to a tetrameric structure in the presence of the TTRs native ligand, thyroxine, as shown by gel filtration chromatography, native gel electrophoresis, TTR antibody recognition and thyroid hormone binding. In the current study the solution structure of the first of these fragment peptides, TTR(151) is examined to determine its intrinsic propensity to form beta-sheet structure, potentially involved in amyloid fibril formation by TTR. Despite the presence of extensive beta-structure in the native form of the protein, the Nterminal fragment adopts an essentially random coil conformation in solution