Trastornos respiratorios del sueño en Insuficiencia Cardíaca con fracción de eyección reducida

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Introduction: Sleep-disordered breathing (SDB) are highly prevalent in patients with heart failure (HF). The presence of obstructive sleep apnea syndrome (OSA) determines a worse prognosis in these patients. There are questionnaires aimed at evaluating the probability of OSA, although none have been validated in patients with HF. The primary objective of this study was to establish the prevalence of SDB in a cohort of patients with HF and reduced ejection fraction (HFrEF) from the Multidisciplinary HF Unit (UMIC). As a secondary objective, to evaluate the usefulness of the Stop-Bang, Berlin, and 2ABN3M questionnaires for TRS screening in these patients. Methodology: Cross-sectional, observational study, including the active cohort of the UMIC, over 18 years with HFrEF, clinically stable and informed consent. Patients with cognitive, neurological or hearing impairment with limitations when conducting the interview were excluded. Patients with other limiting or uncontrolled sleep disorders, continuous home oxygen therapy requirements, did not enter the study. Berlin, Stop-Bang, and 2ABN3M questionnaires were administered, classifying the population into high-risk, intermediate-risk, and low-risk groups of presenting SDB. All patients underwent outpatient respiratory polygraphy (RP). Descriptive statistics were used to characterize demographic variables, measures of central tendency and dispersion. SPSS statistical software was used. Results: 387 patients were included, 248 men (64.1%), mean age was 63.5 ± 0.6 years. The etiology of HF was ischemic in 41.6% of patients. The body mass index was 29.3 ± 0.3 kg/m2. LVEF was 34.2 ± 0.5, pro-BNP 1233.8 ± 137.6 pg/ml. The results of the questionnaires showed that 52.1% (198) presented a high risk of SDB according to the Berlin questionnaire. With Stop-Bang, 35.9% (139) were high risk, 42.1% (163) intermediate risk, and the remaining 22% (85) low risk. With the 2ABN3M score, 62% (240) were high risk. A total of 156 respiratory polygraphs (40.3% of the population) were performed. The cut-off point to define the presence of sleep apnea was considered to be an AHI >15. 58.3% (91) of the patients presented TRS. Of these, 95% presented obstructive apnea and 5% central apnea with periodic Cheyne-Stokes breathing. A high percentage (26%) presented AHI greater than 30. The sensitivity of the Berlin and Stop-Bang questionnaires was 75.8% and 91.2%, respectively, with a specificity of 53.8% and 24.6%. Regarding the 2ABN3M score, a sensitivity of 71.4% and a specificity of 44.6% were observed. Conclusions: The prevalence of sleep-disordered breathing in patients with HFrEF was high in our cohort and obstructive apnea predominated. Given the high sensitivity (91.2%) of the Stop-Bang questionnaire found in our study, it could be useful as a screening tool for TRS in this type of patient. The importance of investigating this pathology whose clinical presentation can be non-specific and remain underdiagnosed is highlighted.

Introdução: Os distúrbios respiratórios do sono (DRS) são altamente prevalentes em pacientes com insuficiência cardíaca (IC). A presença da síndrome da apneia obstrutiva do sono (SAOS) determina pior prognóstico nesses pacientes. Existem questionários destinados a avaliar a probabilidade de AOS, porém nenhum foi validado em pacientes com IC. O objetivo primário deste estudo foi estabelecer a prevalência de DRS em uma coorte de pacientes com IC e fração de ejeção reduzida (ICFEr) da Unidade Multidisciplinar de IC (UMIC). Como objetivo secundário, avaliar a utilidade dos questionários Stop-Bang, Berlin e 2ABN3M para triagem de SRT nesses pacientes. Metodologia: Estudo transversal, observacional, inclui a coorte ativa da UMIC, maiores de 18 anos com ICFEr, clinicamente estável e consentimento informado. Foram excluídos pacientes com deficiência cognitiva, neurológica ou auditiva com limitações na realização da entrevista. Pacientes com outros distúrbios do sono limitantes ou descontrolados, requisitos de oxigenoterapia domiciliar contínua, não entraram no estudo. Os questionários Berlin, Stop-Bang e 2ABN3M foram aplicados, classificando a população em grupos de alto risco, risco intermediário e baixo risco de apresentar DRS. Todos os pacientes foram submetidos à poligrafia respiratória (PR) ambulatorial. A estatística descritiva foi utilizada para caracterizar as variáveis ​​demográficas, medidas de tendência central e dispersão. Foi utilizado o software estatístico SPSS. Resultados: foram incluídos 387 pacientes, 248 homens (64,1%), com idade média de 63,5 ± 0,6 anos. A etiologia da IC foi isquêmica em 41,6% dos pacientes. O índice de massa corporal foi de 29,3 ± 0,3 kg/m2. FEVE foi de 34,2 ± 0,5, pro-BNP 1233,8 ± 137,6 pg/ml. Os resultados dos questionários mostraram que 52,1% (198) apresentaram alto risco de DRS de acordo com o questionário de Berlim. Com Stop-Bang, 35,9% (139) eram de alto risco, 42,1% (163) de risco intermediário e os restantes 22% (85) de baixo risco. Com a pontuação 2ABN3M, 62% (240) eram de alto risco. Foram realizados 156 polígrafos respiratórios (40,3% da população). O ponto de corte para definir a presença de apneia do sono foi considerado um IAH >15. 58,3% (91) dos pacientes apresentaram SRT. Destes, 95% apresentavam apnéia obstrutiva e 5% apnéia central com respiração Cheyne-Stokes periódica. Uma alta porcentagem (26%) apresentou IAH maior que 30. A sensibilidade dos questionários Berlin e Stop-Bang foi de 75,8% e 91,2%, respectivamente, com especificidade de 53,8% e 24,6%. Em relação ao escore 2ABN3M, observou-se sensibilidade de 71,4% e especificidade de 44,6%. Conclusões: A prevalência de distúrbios respiratórios do sono em pacientes com ICFEr foi alta em nossa coorte, com predominância de apneias obstrutivas. Dada a alta sensibilidade (91,2%) do questionário Stop-Bang encontrado em nosso estudo, ele pode ser útil como uma ferramenta de triagem para ERT nesse tipo de paciente. Ressalta-se a importância da investigação dessa patologia cuja apresentação clínica pode ser inespecífica e permanecer subdiagnosticada.

Fraud triangle and earnings management based on the modified M-score: A study on manufacturing company in Indonesia.

This study combines the concept of a fraud triangle and a modified Beneish M-score to detect factors that trigger earnings management. The modified M-score formula used in this study contains five original and four additional ratios. A sample of 284 manufacturing companies listed on the Indonesia Stock Exchange in the period 2017-2019 is used. Based on the logistic regression test and t-test, the results show that asset growth, changes in receivables to sales, and auditor changes have a negative relationship and debt ratio has a positive relationship with earnings management. In addition, return on assets has no relationship with earnings management. In other words, manipulator firms are subject to greater pressure on leverage and have fewer independent commissioners. This study is the first to utilise the modified Beneish M-score model to detect earnings management in manufacturing companies in Indonesia. The effectiveness of this model makes it a valuable tool in detecting fraud and is expected to be useful for future research.

USAGE OF DIGITAL D CHART TEST AS A MODIFICATION OF AMSLER GRID IN OPHTHALMOLOGY AND OPTOMETRY.

AIMS: Metamorphopsia is important symptom of macular disease. The most common simple detection method of metamorphopsia is Amsler grid. Usually it is used monocularly with best correction for near. Patient should evaluate grid deformation a describe position of the deformity. This method is based on qualitative principle. For quantitative evaluation we can use Software D Chart (Thomson Software Solution). This instrument enables evaluate degree and position of the metamorphopsia in central visual field. Our goal was to establish M-score values in group of young healthy subjects without correction (M-score natural), with cylindrical spectacle lens (M-score SL) and in group of patients with age related degeneration (M-score ARMD). OBJECTS AND METHODS: We had 33 probands divided into 2 samples. The first sample contains 15 young probands with average age 23 years without any eye pathology. The second sample contains 18 patients with ARMD (7 with dry form and 11 with wet form). In our study we used software D Chart (Thomson Software Solution). This software was use in Acer PC with touchable screen. We note total M-score in right eye of all probands. Level for statistic evaluation was set on p = 0.05. RESULTS: Natural M-score values for young probands was: median 0, minimum 0, maximum 2.3. With cylindrical lens we got these values: median 25.2, minimum 3.6, maximum 41.6. In second sample with probands suffer from ARMD we got these values: median 0.8, minimum 0, maximum 29.4. Wilcoxon non-parametric test was used for statistical evaluation. We proved statistically significant difference between all variables. M-score natural vs. M-score SL showed p < 0.001, M-score natural vs. M-score ARMD showed p = 0.04 and M-score SL vs. M-score ARMD showed p < 0.001. CONCLUSION: Our study showed statistically significant differences between variable M-score natural, M-score SL and M-score ARMD. We found that printed Amsler grid as well as its digital modification D Chart are suitable for determining metamorphopsia in central visual field. The main advantage of D Chart is quantitative evaluation of the test with M-score and digital registration of retinal changes during patient´s follow up.

Interobserver agreement of digital dermatitis M-scores for photographs of the hind feet of standing dairy cattle.

Digital dermatitis (DD) is the leading infectious cause of lameness in dairy cattle, and it affects their welfare and productivity worldwide. At the herd level, DD is often assessed while cows are standing in a milking parlor, and lesions are most commonly evaluated using the M-score. The objective of this study was to examine the interobserver agreement for M-scores of the feet of standing cattle, based on digital color photographs of dairy cattle hind feet. A total of 88 photographs and written descriptors of the M-score were sent to 11 scorers working at 10 different institutions in 5 countries. The scorers received no formal training immediately before scoring the photographs; however, all regularly used the M-score to score DD. The answers for 36 photographs were excluded from the analysis because the photograph either had more than 1 M-stage as mode or not all scorers assigned an M-score to it. The M-scores of the 11 scorers from 52 photographs were available for analysis. Interobserver agreement was tested using Gwet's agreement coefficient (AC1) and the mode was assumed correct. Overall, moderate agreement emerged for the M-score (AC1 = 0.48). For the individual M-stages, almost perfect agreement existed for M0 (AC1 = 0.99), M1 (AC1 = 0.92), and M3 (AC1 = 0.82), and substantial agreement for M2 (AC1 = 0.61), M4 (AC1 = 0.65), and M4.1 (AC1 = 0.71). This outcome indicates the degree of individual variation in M-scoring in this context by unstandardized, experienced European observers, particularly for the M2, M4, and M4.1 stages. Standardized training is likely to improve the consistency of M-scoring and thus the generalizability of future DD research results on this important endemic disease.

Metamorphopsia change and influence factors before and after idiopathic epiretinal membrane surgery / 中华实验眼科杂志

Objective To investigate the changes of metamorphopsia between before and after surgery in the patients with idiopathic epiretinal membrane and its influence factors.Methods A series cases observitional study included 39 eyes of 39 patients with idiopathic epiretinal membrane.Follow-up was carried out at 1 week before surgery and 3,6 months after surgery respectively.M-chart was used to quantify the severity of metamorphopsia (M-score).EDTRS visual chart was used to quantify best corrected visual acuity (BCVA) (converted to LogMAR).Central subfield thickness (CST),central foveal volumn (CV),cube average thickness (CAT),central foveal thichness (CFT),ganglion cell layer (GCL) thickness,inner nuclear layer (INL) thickness,outer nuclear layer (ONL) and outer plexiform layer (OPL) thickness,the integrity of external limiting membrane,ellipsoid zone and interdigitation zone were analyzed by using spectral domain-optical coherence tomography (OCT).This study protocol was approved by Ethic Committee of Beijing Tongren Hospital (No.TRECKY-012).Written informed consent was obtained from each subject before surgery.Results Mean M-score was significantly decreased from 0.8 (0.3,1.1) before surgery to 0.5 (0.2,0.8) at 3 months after surgery,with a significant difference between the two time points (Z=-2.013,P=0.044).Mean M-score was 0.6(0.2,0.8) at 6 months after surgery,which was not significantly different in comparison with before surgery and 3 months after surgery (Z =-1.873,P =0.061;Z =-0.288,P =0.773).Compared with before surgery,the horizontal M-score was significantly decreased 3 months and 6 months after surgery (Z =-2.329,P =0.020;Z =-2.858,P =0.004).No significant difference was found in vertical M-score among before surgery and 3,6 months after surgery (all at P＞0.05).The BCVA was improved from 0.40 (0.30,0.66) before surgery to 0.20 (0.06,0.42) 3 months after surgery and declined to 0.30 (0.10,0.52) at 6 months after surgery,and significant differences were obtained between 3 months after surgery and before surgery or 6 months after surgery (Z =-4.087,P＜0.001;Z =-2.235,P =0.025).Compared with before surgery,the BCVA in cataract combined with vitrectomy operative group was significantly improved in 3 months and 6 months after surgery (Z=-2.613,P=0.009;Z=-2.466,P=0.014) and the BCVA in only vitrectomy group was significantly improved at 3 months after surgery but decreased 6 months after surgery,showing significant differences between 3 months after surgery and before surgery or 6 months after surgery (Z =-3.104,P =0.002;Z =-3.464,P =0.001).Preoperative M-score was positively correlated with preoperative BCVA,preoperative CST or preoperative CFT (rs =0.384,P =0.016;rs =0.585,P＜0.001;rs =0.601,P＜0.001).No correlation was found between BCVA with GCL,INL or ONL + OPL thickness.Horizontal M-score was positively correlated with CST,postoperative CV and postoperative CAT (rs=0.322,P=0.045;rs=0.340,P=0.034;rs =0.336,P=0.036),and no correlation was found between horizontal M-score and BCVA,CFT,GCL thickness,INL thickness,ONL+OPL thickness in 6 months after surgery.The vertical M-score and mean M-score were not correlated with OCT parameters in 6 months after surgery.The mean M-score was positively correlated with preoperative mean M-score,preoperative CST,preoperative CV,preoperative CAT in 6 months after surgery (rs =0.589,P＜0.001;rs =0.330,P =0.040;rs =0.404,P =0.011;rs =0.410,P =0.009).In addition,and no significant correlation between mean M-score and preoperative BCVA,CFT,GCL thickness,INL thickness,ONL+OPL thickness.Multivariate stepwise linear regression showed that preoperative M-score was a predictor of postoperative M-values (adjusted R2 =0.211,P =0.002).Conclusions Most metamorphopsia can be alleviated after idiopathic epiretinal membrane surgery.The residue metamorphopsia after surgery probably is correlated with preoperative metamorphopsia and CFT.

Microsphere-Based Assessment of DNA Methylation for AML Prognosis.

Epigenetic dysregulation, including aberrant methylation of cytosine residues in DNA, is a hallmark of cancer and clearly results in oncogenic cellular alterations such as transcriptional attenuation of tumor suppressors and genomic instability. A number of studies have examined DNA methylation alterations in patients with acute myeloid leukemia (AML) and have shown that analysis of multilocus methylation patterns can identify biologically distinct AML subclasses and can predict patient prognosis. In order to utilize the prognostic capability of methylation analysis in a clinical setting, we have developed a microsphere-based HpaII tiny fragment enrichment by ligation-mediated PCR (xMELP) assay to interrogate the methylation state of genomic multiple loci along with a random forest-based classification algorithm that correlates DNA methylation status with patient prognosis. These tools can be easily implemented in a clinical molecular pathology laboratory and can be utilized for more accurate risk stratification of AML patients.

Lesion-to-Eloquent Fiber Distance Is a Crucial Risk Factor in Presurgical Evaluation of Arteriovenous Malformations in the Temporo-occipital Junction.

OBJECTIVE: Temporo-occipital junction arteriovenous malformations (TOJ-AVMs) do not often involve eloquent brain cortex, but rather exist beside functional fiber tracts. The objective of this study was to determine the outcomes after surgical treatment in patients with TOJ-AVMs and to identify risk factors associated with postoperative neurologic deficits. METHODS: We retrospectively studied 41 patients with TOJ-AVMs. All patients underwent preoperative diffusion tensor imaging. Every potentially involved function (visual field and language) was studied as an independent function object (FO). The function-related optic radiation or arcuate fasciculus was tracked. Lesion-to-eloquent fiber distances (LFDs) were analyzed in regard to postoperative neurologic deficits. The areas under the receiver operating characteristic curves were compared. RESULTS: There were 58 FOs analyzed. Of these, 26 (44.8%) FOs led to short-term neurologic deficits, and 21 (36.2%) FOs resulted in long-term neurologic deficits. LFD was a significant predictor of short-term (P = 0.002) and long-term (P = 0.007) neurologic deficits. The Spetzler-Martin (S-M) score was associated with short-term neurologic deficits (P = 0.045), but it was not associated with long-term neurologic deficits. The area under the receiver operating characteristic curve of LFD was higher than that of the S-M score in predicting short-term neurologic deficits (0.89 vs. 0.72, P = 0.04) and long-term neurologic deficits (0.90 vs. 0.62, P = 0.002). The cutoff point for LFD in predicting long-term neurologic deficits was 3.10 mm. CONCLUSIONS: Patients with TOJ-AVMs have a high risk of surgical morbidity, although they often have relatively low S-M scores; LFD is a crucial risk factor associated with postoperative neurologic deficits in patients with TOJ-AVMs.

Investigating the genetic background of bovine digital dermatitis using improved definitions of clinical status.

Bovine digital dermatitis (DD) is an increasing claw health problem in all cattle production systems worldwide. The objective of this study was to evaluate the use of an improved scoring of the clinical status for DD via M-scores accounting for the dynamics of the disease; that is, the transitions from one stage to another. The newly defined traits were then subjected to a genetic analysis to determine the genetic background for susceptibility to DD. Data consisted of 6,444 clinical observations from 729 Holstein heifers in a commercial dairy herd, collected applying the M-score system. The M-score system is a classification scheme for stages of DD that allows a macroscopic scoring based on clinical inspections of the bovine foot, thus it describes the stages of lesion development. The M-scores were used to define new DD trait definitions with different complexities. Linear mixed models and logistic models were used to identify fixed environmental effects and to estimate variance components. In total, 68% of all observations showed no DD status, whereas 11% were scored as infectious for and affected by DD, and 21% of all observations exhibited an affected but noninfectious status. For all traits, the probability of occurrence and clinical status were associated with age at observation and period of observation. Risk of becoming infected increased with age, and month of observation significantly affected all traits. Identification of the optimal month concerning DD herd status was consistent for all trait definitions; the last month of the trial was identified. In contrast, months exhibiting the highest least squares means of transformed scores differed depending on trait definition. In this respect, traits that can distinguish between healthy, infectious, and noninfectious stages of DD can account for the infectious potential of the herd and can serve as an alert tool. Estimates of heritabilities of traits studied ranged between 0.19 (±0.11) and 0.52 (±0.17), revealing a tendency for higher values for more complex trait definitions. In terms of genetic selection, all trait definitions identified the best (i.e., most resistant) animals, but only the new trait definitions were able to distinguish between animals with average and high predispositions for DD. Considering repeated measurements resulted in heritability estimates ranging between 0.13 (±0.05) and 0.29 (±0.10).

Detection of proneural/mesenchymal marker expression in glioblastoma: temporospatial dynamics and association with chromatin-modifying gene expression.

Proneural and mesenchymal are two subtypes of glioblastoma identified by gene expression profiling. In this study, the primary aim was to detect markers to develop a clinically applicable method for distinguishing proneural and mesenchymal glioblastoma. The secondary aims were to investigate the temporospatial dynamics of these markers and to explore the association between these markers and the expression of chromatin-modifying genes. One hundred thirty-three glioma samples (grade II: 14 samples, grade III: 18, grade IV: 101) were analyzed. We quantified the expression of 6 signature genes associated with proneural and mesenchymal glioblastoma by quantitative reverse transcription-polymerase chain reaction. We assigned proneural (PN) and mesenchymal (MES) scores based on the average of the 6 markers and calculated a predominant metagene (P-M) score by subtracting the MES from the PN score. We used these scores to analyze correlations with malignant transformation, tumor recurrence, tumor heterogeneity, chromatin-modifying gene expression, and HDAC7 expression. The MES score positively correlated with tumor grade, whereas the PN score did not. The P-M score was able to distinguish the proneural and mesenchymal subtypes. It was decreased in cases of tumor recurrence and malignant transformation and showed variability within a tumor, suggesting intratumoral heterogeneity. The PN score correlated with the expression of multiple histone-modifying genes, whereas the MES score was associated only with HDAC7 expression. Thus, we demonstrated a simple and straightforward method of quantifying proneural/mesenchymal markers in glioblastoma. Of note, HDAC7 expression might be a novel therapeutic target in glioblastoma treatment.

Metamorphopsia before and after full-thickness macular hole surgery.

PURPOSE: We quantified the degree and dynamics of metamorphopsia changes in patients subjected to full-thickness macular hole surgery. MATERIAL/METHODS: This prospective interventional case series included 10 eyes of 10 patients with full-thickness macular hole (mean age 66.2±6.0 years). The patients underwent a complete ophthalmological examination including SD-OCT. The severity of metamorphopsia (expressed as M-score) was evaluated with M-CHARTS. 20-gauge pars plana vitrectomy with trypan blue staining, internal limiting membrane peeling and 20% sulphur hexafluoride tamponade was performed. Time course of metamorphopsia changes and their relation to best corrected visual acuity (BCVA) and OCT parameters were assessed. RESULTS: Significant but not total M-score decrease was observed one month postoperatively (0.72±0.44 vs. 0.50±0.36, z=-2.207, p=0.0353, power=0.26, pre- vs. post-op), with subsequent stabilization (0.41±0.41 three months and 0.37±0.44 six months post-op). The differences between M-score one month, three months and six months postoperatively were not significant. Baseline M-score correlated significantly with postoperative values at three follow-ups (rho=0.853, 0.715, 0.847; p<0.05 for all; power=0.94, 0.58, 0.79). Baseline M-score did not correlate with macular hole dimensions (including basis p=0.154, minimal diameter p=0.051 or height of the border p=0.700). No correlation between M-score and the following parameters was found either pre- or postoperatively: BCVA, central foveal thickness, central subfield macular thickness and central subfield macular volume. CONCLUSIONS: In patients with successfully operated full-thickness macular hole, M-score decreased as early as one month postoperatively and was stable afterwards. The baseline M-score was a prognostic factor for the postoperative M-score. M-score turned out to be independent from BCVA and macular hole dimensions.