Browsing by Issue Date, starting with "2018-08"
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- Analysis of electroencephalogram-derived indexes for anesthetic depth monitoring in pediatric patients with intellectual disability undergoing dental surgeryPublication . Silva, A.; Amorim, P.; Felix, L.; Abelha, F.; Mourão, J.Background: Patients with intellectual disability (ID) often require general anesthesia during oral procedures. Anesthetic depth monitoring in these patients can be difficult due to their already altered mental state prior to anesthesia. In this study, the utility of electroencephalographic indexes to reflect anesthetic depth was evaluated in pediatric patients with ID. Methods: Seventeen patients (mean age, 9.6 ± 2.9 years) scheduled for dental procedures were enrolled in this study. After anesthesia induction with propofol or sevoflurane, a bilateral sensor was placed on the patient's forehead and the bispectral index (BIS) was recorded. Anesthesia was maintained with sevoflurane, which was adjusted according to the clinical signs by an anesthesiologist blinded to the BIS value. The index performance was accessed by correlation (with the end-tidal sevoflurane [EtSevo] concentration) and prediction probability (with a clinical scale of anesthesia). The asymmetry of the electroencephalogram between the left and right sides was also analyzed. Results: The BIS had good correlation and prediction probabilities (above 0.5) in the majority of patients; however, BIS was not correlated with EtSevo or the clinical scale of anesthesia in patients with Lennox-Gastaut, West syndrome, cerebral palsy, and epilepsy. BIS showed better correlations than SEF95 and TP. No significant differences were observed between the left- and right-side indexes. Conclusion: BIS may be able to reflect sevoflurane anesthetic depth in patients with some types of ID; however, more research is required to better define the neurological conditions and/or degrees of disability that may allow anesthesiologists to use the BIS.
- Glomerular filtration rate change during chronic hepatitis C treatment with Sofosbuvir/Ledipasvir in HCV/HIV Coinfected patients treated with Tenofovir and a boosted protease inhibitor: an observational prospective studyPublication . Soeiro, C.; Gonçalves, C.; Marques, M.; Méndez, M.; Tavares, A.; Horta, A.; Sarmento-Castro, R.INTRODUCTION: Concomitant use of ledipasvir and boosted protease inhibitors (PIs) may increase the risk of tenofovir (TDF) nephrotoxicity, since both these drugs increase TDF levels. Our aim was to evaluate glomerular filtration rate (eGFR) evolution during HCV treatment with sofosbuvir/ledipasvir (SOF/LDV) in HCV/HIV coinfected patients, according to their antiretroviral treatment (ARV). METHODS: Observational prospective study of HCV/HIV coinfected patients treated with SOF/LDV. eGFR evolution was evaluated during and 12 weeks after HCV treatment. Patients were categorized in three groups based on ARV regimen: non TDF, non-boosted TDF and TDF + boosted PI. RESULTS: We included 273 patients: 145 were receiving a non-TDF regimen, 78 a non-boosted TDF scheme and 50 were receiving TDF + boosted PI. We observed a statistically significant decrease in eGFR during treatment in all groups (non TDF p = 0.03, 95%CI [0.23-3.86], non-boosted TDF p < 0.01, 95%CI [3.36-7.44], TDF + PI p = 0.01, 95%CI [1.09-7.53]). The decrease was more pronounced in those receiving unboosted TDF (- 5.40 ml/min/1.73m2), but differences in eGFR decrease between the three groups were small and not statistically different (p = 0.06). eGFR decrease was greater in patients treated for 24 weeks (p = 0.009) and in cirrhotic patients (p = 0.036). At the end of follow up a recovery of eGFR was observed in all groups. CONCLUSION: We observed a significant decrease in eGFR during treatment in all study groups, that was small and reversible after SOF/LDV discontinuation. TDF was not associated with an increase in renal toxicity.
- Alternative method of outside-in meniscal repair for anterior horn tearsPublication . Serrano, P.; Amorim-Barbosa, T.; Santos-Silva, M.; Sousa, R.Treatment of symptomatic meniscal tears continues to evolve as we improve our understanding of the biomechanical role of the meniscus and its long-term importance to the health of the knee joint. Suture repair of meniscal tears is challenging and continues to rise as we aim to preserve meniscal tissue. Outside-in meniscal suture techniques may involve using expensive equipment that is not readily available for immediate use in most operating rooms. Aware of the different techniques available, the authors describe a fast and reproducible technique that does not require the use of specific material or equipment.
- Visceral Obesity and Metabolic Syndrome Are Associated with Well-Differentiated Gastroenteropancreatic Neuroendocrine TumorsPublication . Santos, A.; Santos, A.; Castro, C.; Raposo, L.; Pereira, S.; Torres, I.; Henrique, R.; Cardoso, H.; Monteiro, M.The determinants for gastroenteropancreatic neuroendocrine tumors (GEP-NET) recent burden are matters of debate. Obesity and metabolic syndrome (MetS) are well established risks for several cancers even though no link with GEP-NETs was yet established. Our aim in this study was to investigate whether well-differentiated GEP-NETs were associated with obesity and MetS. Patients with well-differentiated GEP-NETs (n = 96) were cross-matched for age, gender, and district of residence with a control group (n = 96) derived from the general population in a case-control study. Patients presented gastro-intestinal (75.0%) or pancreatic (22.9%) tumors, grade G1 (66.7%) or G2 (27.1%) with localized disease (31.3%), regional metastasis (16.7%) or distant metastasis (43.8%) at diagnosis, and 45.8% had clinical hormonal syndromes. MetS was defined according to Joint Interim Statement (JIS) criteria. Well-differentiated GEP-NETs were associated with MetS criteria as well as the individual components' waist circumference, fasting triglycerides, and fasting plasma glucose (p = 0.003, p = 0.002, p = 0.011 and p < 0.001, respectively). The likelihood of the association was higher when the number of individual MetS components was greater than four. MetS and some individual MetS components including visceral obesity, dyslipidemia, and increased fasting glucose are associated with well-differentiated GEP-NET. This data provides a novel insight in unraveling the mechanisms leading to GEP-NET disease.
- Human notochordal cell transcriptome unveils potential regulators of cell function in the developing intervertebral discPublication . Rodrigues-Pinto, Ricardo; Ward, L.; Humphreys, M.; Zeef, L.; Berry, A.; Hanley, K.; Hanley, N.; Richardson, S.; Hoyland, J.The adult nucleus pulposus originates from the embryonic notochord, but loss of notochordal cells with skeletal maturity in humans is thought to contribute to the onset of intervertebral disc degeneration. Thus, defining the phenotype of human embryonic/fetal notochordal cells is essential for understanding their roles and for development of novel therapies. However, a detailed transcriptomic profiling of human notochordal cells has never been achieved. In this study, the notochord-specific marker CD24 was used to specifically label and isolate (using FACS) notochordal cells from human embryonic and fetal spines (7.5-14 weeks post-conception). Microarray analysis and qPCR validation identified CD24, STMN2, RTN1, PRPH, CXCL12, IGF1, MAP1B, ISL1, CLDN1 and THBS2 as notochord-specific markers. Expression of these markers was confirmed in nucleus pulposus cells from aged and degenerate discs. Ingenuity pathway analysis revealed molecules involved in inhibition of vascularisation (WISP2, Noggin and EDN2) and inflammation (IL1-RN) to be master regulators of notochordal genes. Importantly, this study has, for the first time, defined the human notochordal cell transcriptome and suggests inhibition of inflammation and vascularisation may be key roles for notochordal cells during intervertebral disc development. The molecules and pathways identified in this study have potential for use in developing strategies to retard/prevent disc degeneration, or regenerate tissue.
- The association between 25(OH)D levels, frailty status and obesity indices in older adultsPublication . Sousa-Santos, A.; Afonso, C.; Santos, A.; Borges, N.; Moreira, P.; Padrão, P.; Fonseca, Isabel; Amaral, T.Background: Vitamin D deficiency is common in older adults and has been linked with frailty and obesity, but it remains to be studied whether frail obese older adults are at higher risk of vitamin D deficiency. Therefore, the aim of this study is to explore the association between frailty, obesity indices and serum 25(OH)D concentrations. Methods: 1447 individuals with 65 years or older, participating in a cross-sectional study (Nutrition UP 65) were included. Frailty, according to Fried et al., body mass index (BMI), waist circumference (WC), body roundness index (BRI) and body shape index (ABSI) were evaluated. A stepwise multinomial logistic regression was carried out to quantify the association between 25(OH)D quartiles and independent variables. Results: Median 25(OH)D levels were lower in individuals presenting both frailty and obesity (p<0.001). In the multivariate analysis, pre-frailty (OR: 2.65; 95% CI: 1.63-4.33) and frailty (OR: 3.77; 95% CI: 2.08-6.83) were associated with increased odds of lower 25(OH)D serum levels (first quartile). Regarding obesity indices, the highest categories of BMI (OR: 1.74; 95% CI: 1.06-2.86), WC (OR: 3.46; 95% CI: 1.95-6.15), BRI (OR: 4.35; 95% CI: 2.60-7.29) and ABSI (OR: 3.17 95% CI: 1.86-5.38) were directly associated with lower 25(OH)D serum levels (first quartile). Conclusions: A positive association between frailty or obesity and lower vitamin D levels was found. Moreover, besides BMI and WC, other indicators of body adiposity, such as BRI and ABSI, were associated with lower 25(OH)D serum concentrations.
- Inherited p40phox deficiency differs from classic chronic granulomatous diseasePublication . van de Geer, A.; Nieto-Patlán, A.; Kuhns, D.; Tool, A.; Arias, A.; Bouaziz, M.; de Boer, M.; Franco, J.; Gazendam, R.; van Hamme, J.; van Houdt, M.; van Leeuwen, K.; Verkuijlen, P.; van den Berg, T.; Alzate, J.; Arango-Franco, C.; Batura, V.; Bernasconi, A.; Boardman, B.; Booth, C.; Burns, S.; Cabarcas, .; Bensussan, N.; Charbit-Henrion, F.; Corveleyn, A.; Deswarte, C.; Azcoiti, M.; Foell, D.; Gallin, J.; Garcés, C.; Guedes, M.; Hinze, C.; Holland, S.; Hughes, S.; Ibañez, P.; Malech, H.; Meyts, I.; Moncada-Velez, M.; Moriya, K.; Neves, E.; Oleastro, M.; Perez, L.; Rattina, V.; Oleaga-Quintas, C.; Warner, N.; Muise, A.; López, J.; Trindade, E.; Vasconcelos, J.; Vermeire, S.; Wittkowski, H.; Worth, A.; Abel, L.; Dinauer, M.; Arkwright, P.; Roos, D.; Casanova, J.t; Kuijpers, T.; Bustamante, J.Biallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding the p40phox subunit of the phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40phox-deficient patients from 12 additional families in 8 countries. These patients display 8 different in-frame or out-of-frame mutations of NCF4 that are homozygous in 11 of the families and compound heterozygous in another. When overexpressed in NB4 neutrophil-like cells and EBV-transformed B cells in vitro, the mutant alleles were found to be LOF, with the exception of the p.R58C and c.120_134del alleles, which were hypomorphic. Particle-induced NADPH oxidase activity was severely impaired in the patients' neutrophils, whereas PMA-induced dihydrorhodamine-1,2,3 (DHR) oxidation, which is widely used as a diagnostic test for chronic granulomatous disease (CGD), was normal or mildly impaired in the patients. Moreover, the NADPH oxidase activity of EBV-transformed B cells was also severely impaired, whereas that of mononuclear phagocytes was normal. Finally, the killing of Candida albicans and Aspergillus fumigatus hyphae by neutrophils was conserved in these patients, unlike in patients with CGD. The patients suffer from hyperinflammation and peripheral infections, but they do not have any of the invasive bacterial or fungal infections seen in CGD. Inherited p40phox deficiency underlies a distinctive condition, resembling a mild, atypical form of CGD.
- Blood in a Haab StriaPublication . Lages, V.; Coelho, J.; Abreu, C.; Menéres, M.; Barbosa, I.We describe a case of an asymptomatic and spontaneous intracorneal hemorrhage in an adult with congenital glaucoma and blood collected in a Haab stria.