Uneven vectorial projection is the best explanation for QRS dispersion, not the asynchronic ventricular activation.

BACKGROUND: It is believed that QRS dispersion (QRSd) is caused by asynchrony of ventricular activation, but there are no studies that prove it. OBJECTIVES: To determine the mechanism that best explains QRSd in surface electrocardiogram (ECG). METHODS: Cross-sectional study in 95 consecutive patients (median age: 31.0 years [25-52], female sex: 66.3%) with atrioventricular nodal reentrant tachycardia. All 12 ECG leads were recorded at once, simultaneously with the intracardiac recordings. QRSd was quantified as the difference between maximum (QRSmax) and minimum QRS duration (QRSmin). QRS was measured firstly at a calibration of 20 mm/mV and a sweep speed of 50 mm/s, enhancement 10× (basic measurement [BM]), and after at sweep speed of 150 mm/s, enhancement 80 - 160×. The interventricular dyssynchrony (IVD) was also quantified. RESULTS: QRSmax increased from BM (98 ms [91-103]) to 80× (102 ms [99-108]; p = 0.029) and 160× (104 ms [101.5-110]; p = 0.027). QRSmin, almost equaled the duration of QRSmax at 160× (103 ms [100-108]). With BM, QRSd was 26 ms [22-35] and was reduced 26-fold (p < 0.001) by magnifying the QRS at 160× (1 ms [0-3]). IVD was weakly correlated with QRSd (r = 0.234, p = 0.023), but strongly with the total QRS at 160× (r = 0.676, p < 0.001). CONCLUSION: When QRS complex is narrow, the best explanation for the origin of QRSd on the surface ECG is the unequal projection of the ventricular depolarization vector in the different axis of the leads.

Vectorial theory surpasses the local theory in explaining the origin of P-wave dispersion.

BACKGROUND: Local theory and the vectorial theory are used to explain the origin of P-wave dispersion (PWD). There are no previous studies that analyze both at the same time. OBJECTIVES: We set out to determine the implication of local and vectorial theories in the origin of PWD. METHODS: Cross-sectional study in 153 randomly selected patients aged 18-70 years, undergoing electrophysiological study. Inhomogeneous atrial conduction was evaluated by atrial electrogram dispersion in terms of duration (EGMdurdis) and morphology (EGMmorph dis). P-distal coronary sinus interval (P-DCS) was also measured. P-wave was measured twice, firstly at a calibration of 20 mm/mV and a sweep speed of 50 mm/s, enhancement 10× (basic measurement [BM]), and second time at sweep speed of 150 mm/s, enhancement 80-160× (high precision measurement [HPM]). RESULTS: PWD with BM was 48 ms [36-54 ms] while with HPM it was 4 ms [0-10 ms], p < 0.001. With BM, maximum and minimum P- wave duration presented a moderate correlation (r = 0.342; p < 0.001), using HPM it becomes strong (r = 0.750; p < 0.001). In cases with P-DCS < 80 ms (r = 0.965; p < 0.001), but not with P-DCS ≥ 80 ms (r = 0.649; p < 0.001), the previous correlation became almost perfect with HPM. EGMdurdis and EGMmorphdis were weak but significantly correlated with PWD. This correlation became moderate in patients with P-DCS ≥ 80 ms and disappeared in those with P-DCS, using BM and HPM. CONCLUSION: Vectorial theory explains almost entirely the PWD phenomenon. Inhomogeneous conduction could be an additional mechanism to explain PWD, but its contribution is small.

New Parameter of the Second Half of the P-Wave, P-Wave Duration, and Atrial Conduction Times Predict Atrial Fibrillation during Electrophysiological Studies.

OBJECTIVE: Several P-wave parameters reflect atrial conduction characteristics and have been used to predict atrial fibrillation (AF). The aim of this study was to determine the relationship between maximum P-wave duration (PMax) and new P-wave parameters, with atrial conduction times (CT), and to assess their predictive value of AF during electrophysiological studies (AF-EPS). SUBJECTS AND METHODS: This was a cross-sectional study in 153 randomly selected patients aged 18-70 years, undergoing EPS. The patients were divided into 2 groups designated as no AF-EPS and AF-EPS, depending on whether AF occurred during EPS or not. Different P-wave parameters and atrial CT were compared for both study groups. Subsequently, the predictive value of the P-wave parameters and the atrial CT for AF-EPS was evaluated. RESULTS: The values of CT, PMax, and maximum Ppeak-Pend interval (Pp-eMax) were significantly higher in patients with AF-EPS. Almost all P-wave parameters were correlated with the left CT. PMax, Pp-eMax, and CT were univariate and multivariate predictors of AF-EPS. The largest ROC area was presented by interatrial CT (0.852; p < 0.001; cutoff value: ≥82.5 ms; sensitivity: 91.1%; specificity: 81.1%). Pp-eMax showed greater sensitivity (79.5%) to discriminate AF-EPS than PMax (72.7%), but the latter had better specificity (60.4% vs. 41.5%). CONCLUSIONS: Left atrial CT were directly and significantly correlated with PMax and almost all the parameters of the second half of the P-wave. CT, PMax, and Pp-eMax (new parameter) were good predictors of AF-EPS, although CT did more robustly.

Gasto catastrófico en salud en México y sus factores determinantes, 2002-2014.

OBJECTIVE: To assess the financial protection of public health insurance by analyzing the percentage of households with catastrophic health expenditure (HCHE) in Mexico and its relationship with poverty status, size of locality, federal entity, insurance status and items of health spending. METHOD: Mexican National Survey of Income and Expenditures 2002-2014 was used to estimate the percentage of HCHE. Through a probit model, factors associated with the occurrence of catastrophic spending are identified. Analysis was performed using Stata-SE 12. RESULTS: In 2014 there were 2.08% of HCHE (1.82-2.34%; N = 657,474). The estimated probit model correctly classified 98.2% of HCHE (Pr (D) ≥ 0.5). Factors affecting the catastrophic expenditures were affiliation, presence of chronic disease, hospitalization expenditure, rural condition and that the household is below the food poverty line. CONCLUSIONS: The percentage of HCHE decreased in recent years, improving financial protection in health. This decline seems to have stalled, keeping inequities in access to health services, especially in rural population without affiliation to any health institution, below the food poverty line and suffering from chronic diseases.

Utility of inline milk fat and protein ratio to diagnose subclinical ketosis and to assign propylene glycol treatment in lactating dairy cows.

The objective was to identify a fat-to-protein ratio (FPR) cut-off to diagnose subclinical ketosis (SCK) and to evaluate the effect of propylene glycol (PPG) treatment of cows with high FPR. The optimized cut-off was > 1.42; sensitivity (Se) = 92%; specificity (Sp) = 65%. A cut-off > 1.5 was selected for the PPG trial for balanced Se-Sp. Fat-to-protein ratio cut-offs > 1.25, 1.35, 1.50, 1.60, and 1.70 resulted in Se-Sp of 100% to 49%, 96% to 59%, 75% to 78%, 33% to 90%, and 8% to 96%, respectively. The proportions of cows with FPR > 1.25, 1.35, 1.42, 1.50, 1.60, and 1.70 were 60%, 50%, 44%, 30%, 14%, and 6%, respectively. Incidences of clinical ketosis and milk yield were similar between cows that received 400 mL of PPG (n = 34) and control cows (n = 38). Prevalence of SCK at enrollment was 29.2%; therefore, FPR > 1.5 is not indicated for treatment. Lower cut-offs should be used for screening.

Utilité du ratio de matière grasse et de protéine sur la ligne de traite pour diagnostiquer une cétose subclinique et assigner le traitement au propylèneglycol chez les vaches laitières en lactation. L'objectif consistait à identifier un seuil du ratio de matière grasse et de protéine (RMGP) pour diagnostiquer une cétose subclinique et évaluer l'effet du traitement au propylèneglycol (PPG) chez les vaches présentant un RMGP élevé. Le seuil optimisé était de > 1,42; la sensibilité (Se) = 92 %; la spécificité (Sp) = 65 %. Un seuil de > 1,5 a été choisi pour l'essai au PPG pour des Se-Sp équilibrées. Des seuils de ratios de matière grasse et protéine de > 1,25, 1,35, 1,50, 1,60 et 1,70 ont produit des Se-Sp de 100 % et 49 %, de 96 % et 59 %, 75 % et 78 %, de 33 % et 90 % et de 8 % et 96 %, respectivement. Les proportions des vaches avec un RMGP de > 1,25, 1,35, 1,42, 1,50, 1,60 et 1,70 étaient de 60 %, 50 %, 44 %, 30 %, 14 % et 6 %, respectivement. L'incidence de cétose clinique et la production de lait étaient semblables entre les vaches qui avaient reçu 400 mL de PPG (n = 34) et les vaches témoins (n = 38). La prévalence de cétose subclinique au recrutement était de 29,2 %; par conséquent, un RMGP de > 1,5 n'est pas indiqué pour le traitement. Des seuils inférieurs devraient être utilisés pour le dépistage.(Traduit par Isabelle Vallières).

External validation of a minimal-resource model to predict reduced estimated glomerular filtration rate in people with type 2 diabetes without diagnosis of chronic kidney disease in Mexico: a comparison between country-level and regional performance.

Background: Patients with type 2 diabetes are at an increased risk of chronic kidney disease (CKD) hence it is recommended that they receive annual CKD screening. The huge burden of diabetes in Mexico and limited screening resource mean that CKD screening is underperformed. Consequently, patients often have a late diagnosis of CKD. A regional minimal-resource model to support risk-tailored CKD screening in patients with type 2 diabetes has been developed and globally validated. However, population heath and care services between countries within a region are expected to differ. The aim of this study was to evaluate the performance of the model within Mexico and compare this with the performance demonstrated within the Americas in the global validation. Methods: We performed a retrospective observational study with data from primary care (Clinic Specialized in Diabetes Management in Mexico City), tertiary care (Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán) and the Mexican national survey of health and nutrition (ENSANUT-MC 2016). We applied the minimal-resource model across the datasets and evaluated model performance metrics, with the primary interest in the sensitivity and increase in the positive predictive value (PPV) compared to a screen-everyone approach. Results: The model was evaluated on 2510 patients from Mexico (primary care: 1358, tertiary care: 735, ENSANUT-MC: 417). Across the Mexico data, the sensitivity was 0.730 (95% CI: 0.689 - 0.779) and the relative increase in PPV was 61.0% (95% CI: 52.1% - 70.8%). These were not statistically different to the regional performance metrics for the Americas (sensitivity: p=0.964; relative improvement: p=0.132), however considerable variability was observed across the data sources. Conclusion: The minimal-resource model performs consistently in a representative Mexican population sample compared with the Americas regional performance. In primary care settings where screening is underperformed and access to laboratory testing is limited, the model can act as a risk-tailored CKD screening solution, directing screening resources to patients who are at highest risk.

Genomic and Phylogenetic Characterisation of SARS-CoV-2 Genomes Isolated in Patients from Lambayeque Region, Peru.

OBJECTIVE: this study aims to identify and characterise genomic and phylogenetically isolated SARS-CoV-2 viral isolates in patients from Lambayeque, Peru. METHODS: Nasopharyngeal swabs were taken from patients from the Almanzor Aguinaga Asenjo Hospital, Chiclayo, Lambayeque, Peru, which had been considered mild, moderate, and severe cases of COVID-19. Patients had to have tested positive for COVID-19, using a positive RT-PCR for SARS-CoV-2. Subsequently, the SARS-CoV-2 complete viral genome sequencing was carried out using Illumina MiSeq®. The sequences obtained from the sequence were analysed in Nextclade V1.10.0 to assign the corresponding clades, identify mutations in the SARS-CoV-2 genes and perform quality control of the sequences obtained. All sequences were aligned using MAFFT v7.471. The SARS-CoV-2 isolate Wuhan NC 045512.2 was used as a reference sequence to analyse mutations at the amino acid level. The construction of the phylogenetic tree model was achieved with IQ-TREE v1.6.12. RESULTS: It was determined that during the period from December 2020 to January 2021, the lineages s C.14, C.33, B.1.1.485, B.1.1, B.1.1.1, and B.1.111 circulated, with lineage C.14 being the most predominant at 76.7% (n = 23/30). These lineages were classified in clade 20D mainly and also within clades 20B and 20A. On the contrary, the variants found in the second batch of samples of the period from September to October 2021 were Delta (72.7%), Gamma (13.6%), Mu (4.6%), and Lambda (9.1%), distributed between clades 20J, 21G, 21H, 21J, and 21I. CONCLUSIONS: This study reveals updated information on the viral genomics of SARS-CoV-2 in the Lambayeque region, Peru, which is crucial to understanding the origins and dispersion of the virus and provides information on viral pathogenicity, transmission and epidemiology.

First report of Aphrialatifrons (Diptera, Tachinidae, Leskiini) in the Canary Islands.

Background: The Canary Islands are an archipelago of volcanic origin, located off north-west Africa comprising eight islands. Fuerteventura and Lanzarote are the oldest (20 and 15 millon years old, respectively) and the easternmost islands. The order Diptera is one of the most relevant taxa in the Canary Islands as they constitute the second highest species richness. Within this order, the family Tachinidae is especially interesting as all species are endoparasitoids of arthropods and most species play a key role as pollinators. In the Canary Islands, the family comprises 52 species, with Fuerteventura and Lanzarote harbouring up to 20 species each. New information: Aphrialatifrons, a Palaearctic tachinid fly, is reported for the first time from the Canary Islands, where it was found on Fuerteventura and Lanzarote. Morphological examination was carried out and the first known barcode of the species is presented. Its potential distribution and source of origin are discussed.

Hypoxia-Inducible Factor 2 Alpha (HIF2α) Inhibitors: Targeting Genetically Driven Tumor Hypoxia.

Tumors driven by deficiency of the VHL gene product, which is involved in degradation of the hypoxia-inducible factor subunit 2 alpha (HIF2α), are natural candidates for targeted inhibition of this pathway. Belzutifan, a highly specific and well-tolerated HIF2α inhibitor, recently received FDA approval for the treatment of nonmetastatic renal cell carcinomas, pancreatic neuroendocrine tumors, and central nervous system hemangioblastomas from patients with von Hippel-Lindau disease, who carry VHL germline mutations. Such approval is a milestone in oncology; however, the full potential, and limitations, of HIF2α inhibition in the clinic are just starting to be explored. Here we briefly recapitulate the molecular rationale for HIF2α blockade in tumors and review available preclinical and clinical data, elaborating on mutations that might be particularly sensitive to this approach. We also outline some emerging mechanisms of intrinsic and acquired resistance to HIF2α inhibitors, including acquired mutations of the gatekeeper pocket of HIF2α and its interacting partner ARNT. Lastly, we propose that the high efficacy of belzutifan observed in tumors with genetically driven hypoxia caused by VHL mutations suggests that a focus on other mutations that similarly lead to HIF2α stabilization, such as those occurring in neuroendocrine tumors with disruptions in the tricarboxylic acid cycle (SDHA/B/C/D, FH, MDH2, IDH2), HIF hydroxylases (EGLN/PHDs), and the HIF2α-encoding gene, EPAS1, are warranted.

A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings.

BACKGROUND: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data. METHODS: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation. RESULTS: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals. CONCLUSION: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.