There is a paucity of data from large cohort studies examining the prognostic significance of obstructive sleep apnea (OSA) in patients with coronary artery disease. We hypothesized that OSA predicts ...subsequent major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing percutaneous coronary intervention.
The Sleep and Stent Study was a prospective, multicenter registry of patients successfully treated with percutaneous coronary intervention in 5 countries. Between December 2011 and April 2014, 1748 eligible patients were prospectively enrolled. The 1311 patients who completed a sleep study within 7 days of percutaneous coronary intervention formed the cohort for this analysis. Drug-eluting stents were used in 80.1% and bioresorbable vascular scaffolds in 6.3% of the patients, and OSA, defined as an apnea-hypopnea index of ≥15 events per hour, was found in 45.3%. MACCEs, a composite of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned revascularization, occurred in 141 patients during the median follow-up of 1.9 years (interquartile range, 0.8 years). The crude incidence of an MACCEs was higher in the OSA than the non-OSA group (3-year estimate, 18.9% versus 14.0%; p=0.001). Multivariate Cox regression analysis indicated that OSA was a predictor of MACCEs, with an adjusted hazard ratio of 1.57 (95% confidence interval, 1.10-2.24; P=0.013), independently of age, sex, ethnicity, body mass index, diabetes mellitus, and hypertension.
OSA is independently associated with subsequent MACCEs in patients undergoing percutaneous coronary intervention. Evaluation of therapeutic approaches to mitigate OSA-associated risk is warranted.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01306526.
A nondipping blood pressure (BP) pattern is common in patients with obstructive sleep apnea (OSA). However, it is unclear how useful a nondipping BP pattern is in screening for OSA. In this ...cross-sectional study, we recruited consecutive patients with clinical indications for performing ambulatory BP monitoring evaluating the following dipping patterns: (1) normal: ≥10% but <20%; (2) extreme: ≥20%; (3) reduced: ≥0% but <10%; and (4) reverse (riser): <0%. Sleep questionnaires and sleep studies were performed within 7 days after ambulatory BP monitoring. OSA was defined as an apnea-hypopnea index ≥15 events/h. We evaluated 153 patients (OSA frequency, 50.3%). Patients with OSA had higher BPs during sleep, were taking more antihypertensive drugs, and more frequently used hypertensive drugs during the night than patients without OSA. Considering systolic BP, the frequency of OSA in patients with reverse dippers (73.5%) was higher than normal (37.3%), extreme (46.2%), and reduced dippers (49.1%; P=0.012). For diastolic BP, OSA was more common in reduced (66.7%) and reverse dippers (69.6%) as compared to normal (41.4%) or extreme dippers (33.3%; P=0.007). In the regression analysis, reverse systolic dipper was independently associated with OSA (odds ratio, 3.92; 95% CI, 1.31-11.78). Both reduced and reverse diastolic dippers increased the likelihood of OSA for 2.7-fold and 3.5-fold, respectively. Snoring and positive sleep questionnaire findings were associated with a modest increase in the accuracy of reverse dipping pattern for predicting OSA. In conclusion, reverse systolic, as well as reduced and reverse diastolic dippers are independently associated with OSA.
Prosaposin (PSAP) deficiency is an ultra‐rare, fatal infantile lysosomal storage disorder (LSD) caused by variants in the PSAP gene, with seven subjects reported so far. Here, we provide the ...clinical, biochemical and molecular characterization of two additional PSAP deficiency cases. Lysoplex, a targeted resequencing approach was utilized to identify the variant in the first patient, while quantification of plasma lysosphingolipids (lysoSLs), assessed by liquid chromatography mass spectrometry (LC‐MS/MS) and brain magnetic resonance imaging (MRI), followed by Sanger sequencing allowed to attain diagnosis in the second case. Functional studies were carried out on patients' fibroblast lines to explore the functional impact of variants. The two patients were homozygous for two different truncating PSAP mutations (c.895G>T, p.Glu299*; c.834_835delGA, p.Glu278Aspfs*27). Both variants led to a complete lack of processed transcript. LC‐MS/MS and brain MRI analyses consistently provided a distinctive profile in the two children. Quantification of specific plasma lysoSLs revealed elevated levels of globotriaosylsphingosine (LysoGb3) and glucosylsphingosine (GlSph), and accumulation of autophagosomes, due to a decreased autophagic flux, was observed. This report documents the successful use of plasma lysoSLs profiling in the PSAP deficiency diagnosis, as a reliable and informative tool to obtain a preliminary information in infantile cases with complex traits displaying severe neurological signs and visceral involvement.
We analysed the clinical history of 16 hemizygous males affected by Anderson‐Fabry Disease, from four families, to verify their intrafamilial phenotypic variability. Seven male patients, ranging from ...26 to 61 years of age, died, whereas nine (age range 23–55) are alive. Eleven patients have undergone enzyme replacement therapy (ERT) for a period of 5–10 years. We have found a wide range of intrafamilial phenotypic variability in these families, both in terms of target‐organs and severity of the disease. Overall, our findings confirm previous data from the literature showing a high degree of intrafamilial phenotypic variability in patients carrying the same mutation. Furthermore, our results underscore the difficulty in giving accurate prognostic information to patients during genetic counselling, both in terms of rate of disease progression and involvement of different organs, when such prognosis is solely based on the patient's family history.
Xylooligosaccharides (XOS) are nondigestible compounds of great interest for food and pharmaceutical industries due to their beneficial prebiotic, antibacterial, antioxidant, and antitumor ...properties. The market size of XOS is increasing significantly, which makes its production from lignocellulosic biomass an interesting approach to the valorization of the hemicellulose fraction of biomass, which is currently underused. This review comprehensively discusses XOS production from lignocellulosic biomass, aiming at its application in integrated biorefineries. A bibliometric analysis is carried out highlighting the main players in the field. XOS production yields after different biomass pretreatment methods are critically discussed using Microsoft PowerBI® (2.92.706.0) software, which involves screening important trends for decision-making. Enzymatic hydrolysis and the major XOS purification strategies are also explored. Finally, the integration of XOS production into biorefineries, with special attention to economic and environmental aspects, is assessed, providing important information for the implementation of biorefineries containing XOS in their portfolio.
Connexin(Cx)43 is the major gap junction protein present in osteoblasts. We have shown that overexpression of Cx45 in osteoblasts expressing endogenous Cx43 leads to decreased cell-cell communication ...and transcriptional downregulation of several osteoblastic differentiation markers. Here, using the Cx43-null mouse model, we determined whether genetic deficiency of Cx43 affects skeletal development in vivo. Both intramembranous and endochondral ossification of the cranial vault were delayed in the mutant embryos, and cranial bones originating from migratory neural crest cells were also hypoplastic, leaving an open foramen at birth. Cx43-deficient animals also exhibited retarded ossification of the clavicles, ribs, vertebrae, and limbs, demonstrating that skeletal abnormalities are not restricted to a neural crest defect. However, the axial and appendicular skeleton of Cx43-null animals were essentially normal at birth. Cell to cell diffusion of calcein was poor among Cx43-deficient osteoblasts, whose differentiated phenotypic profile and mineralization potential were greatly impaired, compared with wild-type cells. Therefore, in addition to the reported neural crest cell defect, lack of Cx43 also causes a generalized osteoblast dysfunction, leading to delayed mineralization and skull abnormalities. Cell to cell signaling, mediated by Cx43 gap junctions, was critical for normal osteogenesis, craniofacial development, and osteoblastic function.
Anxiety and stress are usually related to the dental treatment situation. The objective was to investigate salivary cortisol and alpha-amylase levels (salivary biomarkers) and heart rate in children ...undergoing a minor dental procedure (dental prophylaxis).
In total, 31 children (range 84-95 months) of both genders without caries or history of dental treatment/pain/trauma were selected. Three saliva samples were gathered: one prior to dental prophylaxis, one immediately after and one ten minutes later. Weight and height were assessed, and heart rate was evaluated prior to and during the procedure. Data were analyzed by correlation tests and t-test/Wilcoxon (alpha = 0.05).
Higher cortisol and amylase levels were observed before prophylaxis compared to afterward. Cortisol and amylase levels did not show a significant correlation, nor did salivary biomarkers and body mass index. However, heart rate and amylase levels showed a significant positive correlation.
In the studied sample, certain anticipation of the dental treatment was observed because higher cortisol and amylase levels were observed before, rather than after the event; moreover a significant correlation between amylase levels and heart rate was observed Thus, salivary biomarkers may be a valuable tool for evaluating anxiety-producing events, such as dental treatment, in children.
To verify the efficacy of nonvisible micropulse diode laser irradiation in the treatment of central serous chorioretinopathy (CSC).
Twenty-two patients with CSC for a total of 24 eyes with a disease ...duration longer than 3 months were included in a prospective study. Patients underwent Early Treatment Diabetic Retinopathy Study visual acuity (VA) examination, dilated ophthalmoscopy, fluorescein angiography, and optical coherence tomography before treatment and during follow- up. Treatment with a micropulse diode laser was given with a duty cycle of 15%. Multiple spots were placed over and adjacent to the area of retinal pigment epithelium leak or decompensation.
Mean follow-up was 14 months (range 3-36 months). Powers used ranged from 1 to 2 W (mean 1.35 W). Mean number of spots was 215 (range 90-400). Fourteen eyes were treated once, nine eyes received two to three treatments, and one eye had five treatments during a follow-up of 3 years. Subretinal fluid was resolved or improved in two third of cases 1 month after laser treatment, and in three-quarters at the end of follow-up. Mean retinal thickness was 328 microm, 197 microm, and 168 microm before, 1 month after irradiation, and at the end of follow-up, respectively. No evidence of RPE or retinal changes due to laser treatment were discernible in most of the eyes. Median VA was 20/32 (range 20/100-20/20) before treatment and 20/25 (range 20/200-20/20) at the end of the follow-up.
Nonvisible micropulse diode laser may have efficacy in the treatment of CSC. A randomized study with larger series is needed.
Argininemia is a rare inherited disorder of the urea cycle because of a deficiency of the enzyme arginase I causing an increase of arginine and guanidino compounds in the blood, urine, and ...cerebrospinal fluid. The clinical picture is characterized by a mild cognitive dysfunction, progressive asymmetrical paraparesis, and seizures. Here, we describe two cases of argininemia where either epilepsia partialis continua (EPC) or nonconvulsive status epilepticus (NCSE) were the presenting manifestations of epilepsy. This is the first report of EPC in an urea cycle disorder. In both the cases, status epilepticus resolved with anticonvulsive drugs. EPC was successfully treated with levetiracetam, and NCSE with valproic acid. No side effects were observed. Because hyperammonemia and NCSE may have the same features of stupor, a neurophysiological approach might prove useful in differentiating these two conditions. Overall, our results strongly indicate that a correct NCSE diagnosis is mandatory to prevent further deterioration in these patients.
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