OSA patients not treated with PAP - Evolution over 5 years according to the Baveno classification and cardiovascular outcomes.

INTRODUCTION: The evolution of patients with obstructive sleep apnea (OSA) non-eligible for PAP-therapy at diagnosis is unknown. Currently, the severity of OSA is based on the apnea-hypopnea index (AHI), but its prognostic relevance has raised concerns. The Baveno classification may allow a better stratification of severity and therapeutic guidance in OSA. METHODS: Patients with AHI≥5/h in 2015, classified into Baveno groups A and B and non-eligible for PAP therapy at diagnosis and over 5 years, were analyzed. Patients were reclassified into Baveno groups (A-D) and changes in groups over 5 years were explored. Patients in Baveno groups C and D, who developed major cardiovascular comorbidities (CVC) or end-organ damage (EOD group), were compared with patients in Baveno groups A and B (non-EOD group). To identify predictors of the development of major CVC or EOD, a logistic regression analysis was performed. RESULTS: There were 76 patients, 58% male, mean age 51.9 ± 10.1 years, mean body mass index (BMI) of 30.3 ± 5.0 kg/m2 and median AHI of 8.9 (5.9-12.0) events/h. At diagnosis, 46% and 54% of patients were classified into Baveno group A and group B, respectively. In total, 21% of patients developed major CVC or EOD (Baveno group C or D); higher age (p = 0.011) and BMI (p = 0.004) and a higher percentage of central apneas (p = 0.012) at diagnosis significantly predicted it, while sex, sleepiness, insomnia, AHI, ODI and T90 were not. CONCLUSIONS: A significant percentage of patients non-eligible for PAP-therapy at diagnosis of OSA developed CVC or EOD; higher age and BMI and a higher percentage of central apneas were significant predictors.

Synthesis and crystal structure of 1-hy-droxy-8-methyl-9H-carbazole-2-carbaldehyde.

Two crystallographically independent mol-ecules are present in the asymmetric unit of the title compound, C14H11NO2, with virtually identical geometries. The carbazole units are planar. The hy-droxy group at position 1, carbaldehyde group at position 2, and methyl group at position 8 (with the exception of two H atoms) are coplanar with the attached benzene rings. The dihedral angle between the two benzene rings is 2.20 (9)° in mol-ecule A and 2.01 (9)° in mol-ecule B. The pyrrole ring makes dihedral angles of 0.82 (10) and 1.40 (10)° [0.84 (10) and 1.18 (10)° in mol-ecule B] with the (-CH3)-substituted and (-OH and -CHO) substituted benzene rings, respectively. The mol-ecular structure is stabilized by the intra-molecular O-H⋯O hydrogen bonds, while the crystal structure features N-H⋯O and C-H⋯O hydrogen bonds. A range of π-π contacts further stabilizes the crystal structure.

[Prognostic value of HbA1c and plasma glucose on one-year mortality in non-diabetic patients after myocardial infarction]. / Impact pronostique de l'HbA1c et de la glycémie plasmatique (Gp) à la phase aiguë d'un infarctus du myocarde sur la mortalité à un an chez des patients non diabétiques.

BACKGROUND: The usefulness of the combined assessment of HbA1c and plasma glucose (PG) in acute myocardial infarction (AMI) in non-diabetic patients remains unclear. PURPOSE: In a large observational study, we aimed to identify the prognostic values of these biomarkers regarding one-year all-cause mortality in non-diabetic patients after AMI. METHODS: From the "obseRvatoire des Infarctus de Côte d'Or" (RICO) survey database, we included all consecutive non-diabetic patients with AMI (n=6617) from May 2001 to December 2016. Exclusion criteria were: admission known or unknown diabetes, in-hospital death. The primary endpoint was all-cause one-year mortality. The secondary endpoints were: MACE, infarct size, LVEF<40% and GRACE risk score. Cut-off levels (high/low) were determined by ROC curve analysis for the prediction of one-year death (HbA1c 5.9% and PG 131mg/dL) to set up 4 groups: low HbA1c/low glucose (n=3158), low HbA1c/high glucose (n=1264), high HbA1c/low glucose (n=1378) and high HbA1c/high glucose (n=817). RESULTS: Elevation of PG was associated with elevated rate of LVEF<40%, STEMI, anterior wall location, DFG<60mL/min/m2 and higher troponin Ic pic (all P<0.001); HbA1c>5.9% was associated with elevated rate of CRP>3mg/L (P<0.001); high HbA1c and high PG together were associated with higher rate of MACE (P<0.001). By multivariate logistic regression analysis, elevated admission PG remained a strong predictor of one-year all-cause [OR (95%CI): 1.64 (1.31-2.05)] mortality and cardiovascular mortality [OR (95%CI): 1.75 (1.33-2.31)], beyond GRACE score [OR (95%CI): 1.03 (1.03-1.04)], as well as elevated HbA1c [OR (95%CI): 1.43 (1.15-1.78) and OR (95%CI): 1.83 (1.39-2.41) respectively]. CONCLUSIONS: Admission PG and HbA1c had strong independent predictive value regarding one-year all-cause mortality in our non-diabetic patients with AMI. These biomarkers could be useful to identify the most-at-risk patients after AMI in order to reduce residual risk in this target population.

Influence of cardiac hemodynamic variables on retinal vessel density measurement on optical coherence tomography angiography in patients with myocardial infarction.

INTRODUCTION: Quantitative measurements of retinal microvasculature by optical coherence tomography angiography (OCT-A) have been used to assess cardiovascular risk profile. However, to date, there are no studies focusing on OCT-A imaging in the setting of the altered hemodynamic status found in high-risk cardiovascular patients. METHODS: To determine the potential association between retinal vascular density on OCT-A and a comprehensive battery of hemodynamic variables in patients with myocardial infarction (MI) using data from the acute phase and at 3 months follow-up after cardiac rehabilitation. This prospective longitudinal study included patients who presented with MI in the cardiology intensive care unit at Dijon University Hospital. Main outcomes and measurements were retinal vessel density on OCT-A, hemodynamic status based on left ventricular ejection fraction (LVEF), and indexed cardiac output during the acute phase of myocardial infarction and at 3 months follow-up. RESULTS: Overall, 30 patients were included in this pilot study. The median (IQR) age was 64 years (55-71) with 87% men. At admission, the mean (SD) LVEF was 53% (11), and the mean indexed cardiac output was 2.70 (0.83) L/min/m2. On OCT-A, the mean inner retinal vascular density was 19.09 (2.80) mm-1. No significant association was found between retinal vascular density and hemodynamic variables. CONCLUSION: We found no significant association between retinal vascular density on OCT-A and hemodynamic variables in the acute phase of a myocardial infarction or after 3 months of cardiac rehabilitation. Therefore, OCT-A findings do not seem to be influenced by the hemodynamic changes associated with myocardial infarction.

Glycaemic variability is associated with severity of coronary artery disease in patients with poorly controlled type 2 diabetes and acute myocardial infarction.

BACKGROUND: In patients with type 2 diabetes (T2D), glycaemic variability (GV), another component of glycaemic abnormalities, is a novel potentially aggravating factor for coronary artery disease (CAD). OBJECTIVES: The aim of our study was to identify interactions between GV and severity of CAD in diabetes patients admitted for acute myocardial infarction (AMI). METHODS: All patients with T2D admitted to our university hospital for AMI from March 2015 to February 2017 who received intravenous (IV) insulin therapy and underwent coronary angiography were included. GV was assessed by mean amplitude of blood glucose excursion (MAGE) values taken within 2 days of admission. Patients with higher GV (highest MAGE tertile) were compared with those with lower GV (first and second MAGE tertiles). RESULTS: A total of 204 patients were included: median age was 72 (61-81) years; 32% were female; HbA1c was 7.3% (6.4-8.2%); diabetes duration was 10 (2-17.5) years; and MAGE value was 0.65 (0.43-0.92) g/L. Compared with those with lower GV, patients with the highest GV were more often women, treated with previous insulin, and had higher blood glucose and HbA1c levels. In addition, patients with elevated GV had significantly higher SYNTAX scores: 17 (10-28) vs. 12 (6-22) (P = 0.009). Indeed, SYNTAX scores (OR: 1.05, 95% CI: 1.02-1.08; P = 0.001) remained independently associated with high GV beyond HbA1c levels (OR: 1.51, 95% CI: 1.2-1.89; P < 0.001). CONCLUSION: In AMI patients with poorly controlled diabetes, GV is associated with CAD severity beyond chronic hyperglycaemia. Although no causality can be determined from our observational study, the results suggest that, in AMI, early evaluation of GV might contribute to the identification of those diabetes patients at high risk, and serve as a therapeutic target for both primary and secondary prevention.

Feasibility of the use of a handheld XRF analyzer to measure skin iron to monitor iron levels in critical organs.

There exists a need for accurate, non-invasive point-of-care tests to detect body iron burden. This study investigated the use of x-ray fluorescence (XRF) measurements of skin iron as a marker for organ iron content in rats. This study also evaluated a novel application of a commercial XRF device, commonly used in mining and construction, as a rapid, portable, and non-invasive measurement tool. Rats (n = 32) were loaded with iron dextran and the iron signal of each animal's skin, liver, and kidney was measured using a conventional XRF system. A quadratic correlation was observed between liver and skin iron signal (R2 = 0.92) and a linear correlation was observed between kidney and skin iron signal (R2 = 0.65). As such, it is concluded that skin iron content can act as a marker for both liver and kidney iron content. The same skin samples were measured using the portable XRF device and compared to the liver and kidney samples measured in the conventional XRF system. Again, a quadratic correlation was observed between liver and skin iron signal (R2 = 0.91) and a linear correlation was observed between kidney and skin iron signal (R2 = 0.83). Thus, the portable XRF device can provide rapid non-invasive, skin XRF measurements. Dosimetry was performed using the portable XRF device to assess the radiological hazard associated with its use. The average skin equivalent dose from this device is 30 ± 10 mSv/min, when the device is collimated and operated at 40 kV. In conclusion, skin iron XRF measurements can act as a surrogate marker for liver iron content, and can be measured using a commercial XRF device for a portable, fast, and non-invasive measurement.

Clinical and molecular markers in COPD.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease, and there is a clinical need for validated markers and biomarkers that can contribute to the assessment of patients, risk prediction, treatment guidance, and assessment of response. Although according to the 2018 GOLD guidelines clinically useful biomarkers for COPD patients in stable condition have yet to be identified, several clinical markers and biomarkers have been proposed for COPD. These include isolated clinical markers, such as symptoms and Health Status assessment, exercise tests, function tests and imaging, and also composite scores and molecular markers. However, and despite strong efforts to identify useful markers in an attempt to improve prognostic and therapeutic approaches, results have not been consistent and expectations of relying on these markers in near future are faint. Current approaches to COPD have shifted from treating the disease to treating the individual patient. There is a clear need to identify treatable traits, focusing more on the patient and not on the disease, in order to implement an increasingly personalized treatment of COPD in the clinic, leading to true precision medicine. There is a need to identify combinations of clinical markers and biomarkers, genetic markers, and phenotypes that can guide the personalized therapy of COPD patients. This critical review will therefore focus not only on currently established markers and biomarkers in COPD but also on possible future approaches toward precision medicine.

Crystal structure of (E)-2-(furan-2-yl-methyl-idene)-2,3,4,9-tetra-hydro-1H-carbazol-1-one.

The title compound, C17H13NO2, crystallizes with two conformationally very similar independent mol-ecules (A and B) in the asymmetric unit. In the crystal, the individual mol-ecules are linked by pairs of N-H⋯O hydrogen bonds forming A-A and B-B inversion dimers, with R22(10) rings. They stack alternately up the a-axis direction and are linked by C-H⋯π inter-actions, forming sheets parallel to the ab plane.

Group O RBCs: where is universal donor blood being used.

BACKGROUND: There have been recurrent shortages of group O blood due to insufficient inventory and use of group O blood in ABO non-identical recipients. We performed a 12-year retrospective study to determine utilization of group O Rh-positive and Rh-negative red blood cells (RBCs) by recipient ABO group. Reasons for transfusing group O blood to ABO non-identical recipients were also assessed. METHODS: Utilization data from all group O Rh-positive and Rh-negative RBCs transfused at three academic hospitals between April 2002 and March 2014 were included. Data were extracted from Transfusion Registry for Utilization Surveillance and Tracking, a comprehensive database with inventory information on all blood products received at the hospitals. Extracted data included product type, ABO and Rh, final disposition (transfused, wasted, outdated), and demographic and clinical data on all patients admitted to hospital. Descriptive statistics were performed using sas 9.3. RESULTS: There were 314 968 RBC transfusions: 151 645 (48·1%) were group O, of which 138 136 (91·1%) RBC units were transfused to group O individuals. ABO non-identical recipients received 13 509 group O RBCs (8·9%). The percentage of group O RBCs transfused to ABO non-identical recipients by fiscal year varied from 7·8% to 11·1% with a steady increase from 2011 to 2013. Reasons for this included: trauma, outdating, outpatient usage and shortages. CONCLUSION: The practice of transfusing O RBCs to non-O individuals has been increasing. Specific hospital and blood supplier policies could be targeted to change practice, leading to a more sustainable group O red blood cell supply.

Romantic, sexual, and sexual risk behaviours of adolescent females with severe obesity.

BACKGROUND: There is an increasing adolescent population with severe obesity with impairments in social and romantic relationships that are seeking clinical weight management, including weight loss surgery (WLS). OBJECTIVE: To document romantic, sexual and sexual risk behaviours in a clinical sample of adolescent females with severe obesity (BMI > 40 kg/m2 ) compared to those of healthy weight (HW). METHODS: This multi-site study-an ancillary to a prospective longitudinal observational study documenting health in adolescents having WLS-presents pre-operative/baseline data from 108 females undergoing WLS, 68 severely obese seeking lifestyle intervention and 118 of HW. Romantic and sexual risk behaviour and birth control information sources were assessed using the Sexual Activities and Attitudes Questionnaire (SAAQ). RESULTS: Severely obese females reported engaging in fewer romantic and sexual behaviours compared to HW. Similar to HW, a subgroup (25%) of severely females were engaging in higher rates of sexual risk behaviours and reported pregnancies and sexually transmitted infections (STIs). A considerable number (28-44%) reported receiving no birth control information from physicians. CONCLUSIONS: Discussion topics with the adolescent patient should extend beyond reproductive health needs (e.g. contraception, unintended pregnancies) to include guidance around navigating romantic and sexual health behaviours that are precursors to these outcomes.

Supersizing pyrrole-modified porphyrins by reversal of the 'breaking and mending' strategy.

While the 'breaking and mending of porphyrin strategy' proved versatile in the generation of a range of pyrrole-modified porphyrins containing 4-, 5-, and 6-membered heterocycles, it failed to access systems incorporating larger rings. A reversal of the strategy - first mending, then breaking - now allowed the formation of a pyrrole-modified porphyrin containing an 8-membered 1,3,6-triazocine-2,4,8-trione heterocycle.

Periodontopathogens antibodies and major adverse events following an acute myocardial infarction: results from the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI).

BACKGROUND: Periodontopathogens antibodies have been shown to be associated with primary myocardial events, but little is known regarding their impact on major adverse events after a prior acute myocardial infarction (AMI). The present prospective study evaluates the association between antibody levels of 4 periodontopathogens and the risk of all-cause death or non-fatal myocardial infarction (MI) at 1 year in 975 patients admitted for acute ST segment or non-ST segment elevation MI in French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI), a nationwide French survey. METHODS: Multiserotype ELISAs were performed to assess levels of IgG and IgA against Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia and Tannerella forsythia. RESULTS: Adjusted HRs indicate the lack of association between IgG-anti-Po. gingivalis levels (0.96 (0.78 to 1.18)), IgA-anti-Po. gingivalis levels (1.13 (0.90 to 1.42)) and the risk of all-cause death or non-fatal MI at 1 year. Additionally, no significant association was found between the occurence of an event at 1 year and immunoglobulins levels against the others periodontopathogens. CONCLUSIONS: The present data indicate that circulating levels of periodontopathogens antibodies are not associated with an increased risk of major adverse events in patients with a prior AMI. Studies dealing with bacterial and clinical data are needed to assess the role of oral health in comprehensive cardiac rehabilitation programmes.

Sequence and structural analyses of NSP4 proteins from human group A rotavirus strains detected in Tunisia.

BACKGROUND: The NSP4 protein of group A rotavirus (RVA) has been recognized as a viral enterotoxin and plays important roles in viral pathogenesis and morphogenesis. Domains involved in structural and functional interactions have been proposed mainly based on the simian SA11 strain. METHODS: NSP4 has been classified into 15 different genotypes (E1-E15), and the aim of this study was to analyze the sequences of 46 RVA strains in order to determine the aminoacid (aa) differences between E1 and E2 genotypes. Another aspect was to characterize the structural and physicochemical properties of these strains. RESULTS: Comparison of deduced aa sequences of the NSP4 protein showed that divergences between NSP4 genotypes E1 and E2 were mostly observed in the VP4-binding, the interspecies variable domain (ISVD) and the double-layered particle (DLP) binding domains. Interestingly, uncommon variations in residues 131 and 138, which are known to be important aa in pathogenesis, were found in one unusual animal derived strain belonging to the E2 genotype. Concerning the structural aspect, no significant differences were noted. CONCLUSION: The presence of punctual aa variations in the NSP4 genotypes may indicate that NSP4 mutates mainly via accumulation of point mutations.

Higher proportion of G2P[4] rotaviruses in vaccinated hospitalized cases compared with unvaccinated hospitalized cases, despite high vaccine effectiveness against heterotypic G2P[4] rotaviruses.

The overall vaccine effectiveness of the monovalent rotavirus vaccine in an observational, prospective, multicentre, hospital-based case-control study in Belgium (RotaBel) was 90%. However, rotavirus genotype and co-infecting pathogens are important parameters to take into account when assessing vaccine effectiveness. In this study we specifically investigated the effect of rotavirus genotypes and co-infecting pathogens on vaccine effectiveness of the monovalent vaccine. In addition, we also investigated the effect of co-infecting pathogens on disease severity. From February 2008 to June 2010 stool samples of rotavirus gastroenteritis cases of a random sample of 39 Belgian hospitals were collected and subsequently genotyped. Fisher's exact tests were performed to investigate the relationships between rotavirus genotype, co-infecting pathogens and disease severity. The vaccine effectiveness of a full series of the monovalent rotavirus vaccine against hospitalized rotavirus gastroenteritis caused by G1P[8] rotavirus strains was 95% (95% CI 77.5-98.7). Against G2P[4], the vaccine effectiveness was 85% (95% CI: 63.7-93.8). G4P[8]- and G3P[8]-specific vaccine effectiveness was 90% (95% CI 19.2-98.7) and 87% (95% CI -5.2 to 98.4), respectively. A post-hoc analysis showed that the genotype distribution was significantly related to the vaccination status (p <0.001), whereby G2P[4] strains were proportionally more prevalent in vaccinated cases than in unvaccinated cases. No statistical associations were found between co-infection status and vaccination status, Vesikari severity score or rotavirus genotype. The high vaccine effectiveness against the individual genotypes implies robust protection of the monovalent rotavirus vaccine against hospitalized rotavirus gastroenteritis caused by the major human rotavirus genotypes. The prevalence of G2P[4] requires continued monitoring.

Clinical challenges of persistent pulmonary air-leaks--case report.

Air leaks are a common problem after pulmonary resection and can be a source of significant morbidity and mortality. The authors describe the case of a 68-year-old male patient who presented with a persistent air-leak after pulmonary resection. Watchful waiting, surgical procedures, as well as medical therapy like pleurodesis and implantation of endobronchial one-way valves on the bronchial segments identified using systematic occlusion of the bronchial segments, were all tried unsuccessfully. During that time the patient remained hospitalized with a chest tube. The instillation of methylene blue through the chest tube was used to identify the segments leading to the persistent air-leak; this enabled successful endobronchial valve placement which sufficiently reduced the size of the air-leak so that the chest tube could be removed. Nonsurgical approaches seem promising and, for some patients may be the only treatment option after all conventional treatments have failed or are considered too high risk.