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.

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.

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.

Bone scintigraphy outperformed anatomic images in frostbite injuries: a case report.

Frostbite is a localized cold thermal injury, as a result of tissue exposure to temperatures below freezing point for a prolonged period of time. The spectrum of injury is broad; thus, frostbite injuries may have deleterious effects with the possibility of losing part or whole extremities. We aim to present the case of a 38-year-old male patient evaluated with multiphase technetium-99m-methylene diphosphonate bone scintigraphy. This methodology may accelerate clinical management of frostbite injuries because it provides precise clinical-imaging correlation by determining the extent of injury and can accurately predict the level of amputation if required.

PET/MR: primary inferior vena cava leiomyosarcoma.

Positron emission tomography (PET) combined with a magnetic resonance (MR) scanner (PET/MR) with 18F-fluorodeoxyglucose (FDG) tracer is being used in quite a few nuclear medicine centers. The aim of this study is to illustrate two uncommon cases of primary inferior vena cava leiomyosarcoma which were formerly evaluated with anatomical images such as computed tomography and ultrasound. These techniques were inferior in the definition of the tumor and its characteristics. F-18 FDG PET/MR was essential and provided all the necessary information: its origin, local extension, anatomo-metabolic behavior, form of presentation, and distant metastasis in one single diagnostic technique. PET/MR accurately contributed to the diagnosis in a shortened period of time and, therefore, in the prognosis of this disease with greater benefits.

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.

A technology assisted precision ketogenic diet intervention for cardio-renal-metabolic health in overweight or obese adults: Protocol for a randomized controlled trial.

BACKGROUND: The obesity epidemic is a public health concern, as it is associated with a variety of chronic conditions. The ketogenic diet has drawn much scientific and public attention. However, implementation is challenging and its effect on cardio-renal-metabolic health is inconclusive. This study will assess the feasibility, acceptability, and preliminary efficacy of a technology-assisted ketogenic diet on cardio-renal-metabolic health. METHODS: This is a single center, 6-month, stratified, randomized controlled trial. A total of 60 overweight/obese adults (18+ years old) will be enrolled, including 20 without type 2 diabetes (T2D) and without chronic kidney disease (CKD); 20 with T2D, but without CKD; and 20 with early-stage CKD. Participants will be stratified based on health conditions and randomized into a ketogenic diet (n = 30) or a low-fat diet group (n = 30). Health education involving diet and physical activity will be delivered both digitally and in-person. Mobile and connected health technologies will be used to track lifestyle behaviors and health indicators, as well as provide weekly feedback. The primary outcome (weight) and the secondary outcomes (e.g., blood pressure, glycemic control, renal health) will be assessed with traditional measurements and metabolomics. DISCUSSION: Mobile and connected health technologies provide new opportunities to improve chronic condition management, health education attendance, planned lifestyle changes and engagement, and health outcomes. The advancement of bioinformatics technology offers the possibility to profile and analyze omics data which may advance our understanding of the underlying mechanisms of intervention effects on health outcomes at the molecular level for personalized and precision lifestyle interventions.

Clonamiento, expresión y seroreactividad de la proteína recombinante de ensamblaje de lipopolisacáridos - D (LptD) de Bartonella bacilliformis / Cloning, expression and seroreactivity of the recombinant lipopolysaccharide assembly protein - D (LptD) from Bartonella bacilliformis

RESUMEN Objetivo. Evaluar in silico y a nivel serológico el potencial antigénico del dominio extracelular recombinante de la proteína de ensamblaje de lipopolisacáridos - D (LptD) de Bartonella bacilliformis (dexr_LptD). Materiales y métodos. Mediante el análisis in silico se realizó la selección de una proteína de B. bacilliformis con potencial antigénico e inmunogénico. El gen de la proteína seleccionada se clonó en Escherichia coli TOP10 y se expresó en Escherichia coli BL21 (DE3) pLysS. La proteína recombinante fue expresada usando isopropil-β-D-1-tiogalactopiranósido (IPTG) y se optimizaron las condiciones de inducción. Por último, se purificó con resina Ni-IDA (His60 Ni Superflow) y se realizó un ensayo de Western Blot. Resultados. In silico, la proteína seleccionada fue LptD por estar localizada en la membrana externa y ser antigénica e inmunogénica. Las condiciones optimizadas para la inducción del dexr_LptD fueron 0,5 mM IPTG, 16 h, medio TB (Terrific Broth), etanol al 3% (v/v), 28 ºC, OD600: 1-1,5 y 200 r.p.m. La purificación se realizó en condiciones denaturantes a pequeña escala y se obtuvo 2,6 µg/mL de dexr_LptD parcialmente purificada. El ensayo de Western Blot mostró una reacción positiva entre los sueros provenientes de pacientes con la enfermedad de Carrión y dexr_LptD, ello evidencia la antigenicidad del dexr_LptD. Conclusiones. El dexr_LptD muestra antigenicidad in silico y a nivel serológico, estos resultados son base para posteriores estudios sobre candidatos vacunales contra la enfermedad de Carrión.

ABSTRACT Objective. To evaluate in silico and at the serological level the antigenic potential of the recombinant extracellular domain of the lipopolysaccharide assembly protein - D (LptD) of Bartonella bacilliformis (dexr_LptD). Materials and Methods. Through in silico analysis, we selected a B. bacilliformis protein with antigenic and immunogenic potential. The selected protein gene was cloned into Escherichia coli TOP10 and expressed in Escherichia coli BL21 (DE3) pLysS. Recombinant protein was expressed using isopropyl-β-D-1-thiogalactopyranoside (IPTG) and induction conditions were optimized. Finally, it was purified with Ni-IDA resin (His60 Ni Superflow) and a Western Blot assay was conducted. Results. In silico, the selected protein was LptD because it is located in the outer membrane and is antigenic and immunogenic. Optimized conditions for dexr_LptD induction were 0.5 mM IPTG, 16 hours, TB (Terrific Broth) medium, 3% (v/v) ethanol, 28 ºC, OD600: 1-1.5 and 200 rpm. Purification was carried out under denaturating conditions on a small scale and we obtained 2.6 μg/mL of partially purified dexr_LptD. The Western Blot assay showed a positive reaction between the sera from patients with Carrión's Disease and dexr_LptD, which shows the antigenicity of dexr_LptD. Conclusions. The dexr_LptD shows antigenicity both in silico and at the serological level, these results are the basis for further studies on vaccine candidates against Carrion's Disease.

Endocrine and Neuroendocrine Tumors Special Issue-Checkpoint Inhibitors for Adrenocortical Carcinoma and Metastatic Pheochromocytoma and Paraganglioma: Do They Work?

Adrenocortical cancers and metastatic pheochromocytomas are the most common malignancies originating in the adrenal glands. Metastatic paragangliomas are extra-adrenal tumors that share similar genetic and molecular profiles with metastatic pheochromocytomas and, subsequently, these tumors are studied together. Adrenocortical cancers and metastatic pheochromocytomas and paragangliomas are orphan diseases with limited therapeutic options worldwide. As in any other cancers, adrenocortical cancers and metastatic pheochromocytomas and paragangliomas avoid the immune system. Hypoxia-pseudohypoxia, activation of the PD-1/PD-L1 pathway, and/or microsatellite instability suggest that immunotherapy with checkpoint inhibitors could be a therapeutic option for patients with these tumors. The results of clinical trials with checkpoint inhibitors for adrenocortical carcinoma or metastatic pheochromocytoma or paraganglioma demonstrate limited benefits; nevertheless, these results also suggest interesting mechanisms that might enhance clinical responses to checkpoint inhibitors. These mechanisms include the normalization of tumor vasculature, modification of the hormonal environment, and vaccination with specific tumor antigens. Combinations of checkpoint inhibitors with classical therapies, such as chemotherapy, tyrosine kinase inhibitors, radiopharmaceuticals, and/or novel therapies, such as vaccines, should be evaluated in clinical trials.

Increased QRS duration and dispersion are associated with mechanical dyssynchrony in patients with permanent right ventricular apical pacing.

BACKGROUND: Permanent right ventricular apical pacing may have negative effects on ventricular function and contribute to development of heart failure. We aimed to assess intra- and interventricular mechanical dyssynchrony in patients with permanent right ventricular apical pacing, and to establish electrocardiographic markers of dyssynchrony. METHODS: 84 patients (46:38 male:female) who required permanent pacing were studied. Pacing was done from right ventricular apex in all patients. We measured QRS duration and dispersion on standard 12-lead ECG. Intra- and interventricular mechanical dyssynchrony and left ventricular ejection fraction were assessed by transthoracic echocardiography. Patients were followed-up for 24 months.  Results: Six months after implantation, QRS duration increased from 128.02 ms to 132.40 ms, p≤0.05. At 24 months, QRS dispersion increased from 43.26 ms to 46.13 ms, p≤0.05. Intra- and interventricular dyssynchrony increased and left ventricular ejection fraction decreased during follow-up. A QRS dispersion of 47 ms predicted left ventricular dysfunction and long-term electromechanical dyssynchrony with a sensitivity of 80% and a specificity of 76%.  Conclusion: In patients with permanent right ventricular apical pacing there is an increased duration and dispersion of QRS related to dyssynchrony and decreased left ventricular ejection fraction. This study shows that QRS dispersion could be a better predictive variable than QRS duration for identifying left ventricular ejection fraction worsening in patients with permanent right ventricular apical pacing. The electrocardiogram is a simple tool for predicting systolic function worsening in these patients and can be used at the bedside for early diagnosis in the absence of clinical symptoms, allowing adjustments of medical treatment to prevent progression of heart failure and improve the patient's quality of life.

Insights into Mechanisms of Pheochromocytomas and Paragangliomas Driven by Known or New Genetic Drivers.

Pheochromocytomas and paragangliomas are rare tumors of neural crest origin. Their remarkable genetic diversity and high heritability have enabled discoveries of bona fide cancer driver genes with an impact on diagnosis and clinical management and have consistently shed light on new paradigms in cancer. In this review, we explore unique mechanisms of pheochromocytoma and paraganglioma initiation and management by drawing from recent examples involving rare mutations of hypoxia-related genes VHL, EPAS1 and SDHB, and of a poorly known susceptibility gene, TMEM127. These models expand our ability to predict variant pathogenicity, inform new functional domains, recognize environmental-gene connections, and highlight persistent therapeutic challenges for tumors with aggressive behavior.

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.

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.

Genotype-Phenotype Features of Germline Variants of the TMEM127 Pheochromocytoma Susceptibility Gene: A 10-Year Update.

PURPOSE: This work aimed to evaluate genotype-phenotype associations in individuals carrying germline variants of transmembrane protein 127 gene (TMEM127), a poorly known gene that confers susceptibility to pheochromocytoma (PHEO) and paraganglioma (PGL). DESIGN: Data were collected from a registry of probands with TMEM127 variants, published reports, and public databases. MAIN OUTCOME ANALYSIS: Clinical, genetic, and functional associations were determined. RESULTS: The cohort comprised 110 index patients (111 variants) with a mean age of 45 years (range, 21-84 years). Females were predominant (76 vs 34, P < .001). Most patients had PHEO (n = 94; 85.5%), although PGL (n = 10; 9%) and renal cell carcinoma (RCC, n = 6; 5.4%) were also detected, either alone or in combination with PHEO. One-third of the cases had multiple tumors, and known family history was reported in 15.4%. Metastatic PHEO/PGL was rare (2.8%). Epinephrine alone, or combined with norepinephrine, accounted for 82% of the catecholamine profiles of PHEO/PGLs. Most variants (n = 63) occurred only once and 13 were recurrent (2-12 times). Although nontruncating variants were less frequent than truncating changes overall, they were predominant in non-PHEO clinical presentations (36% PHEO-only vs 69% other, P < .001) and clustered disproportionately within transmembrane regions (P < .01), underscoring the relevance of these domains for TMEM127 function. Integration of clinical and previous experimental data supported classification of variants into 4 groups based on mutation type, localization, and predicted disruption. CONCLUSIONS: Patients with TMEM127 variants often resemble sporadic nonmetastatic PHEOs. PGL and RCC may also co-occur, although their causal link requires further evaluation. We propose a new classification to predict variant pathogenicity and assist with carrier surveillance.

Atrial conduction explains the occurrence of the P-wave dispersion phenomenon, but weakly.

BACKGROUND: P-wave dispersion (PWD) is believed to be caused by inhomogeneous atrial conduction. This statement, however, is based on limited little solid evidence. The aim of this study was to determine the relationship between atrial conduction and PWD by means of invasive electrophysiological studies. METHODS: Cross-sectional study in 153 patients with accessory pathways and atrioventricular node reentry tachycardia (AVNRT) undergoing an electrophysiological study. Different atrial conduction times were measured and correlated with PWD. RESULTS: Only the interatrial (P-DCS) and left intra-atrial conduction times (ΔDCS-PCS) showed a significant correlation with PWD, but this correlation was weak. Multivariate linear regression analysis determined that both P-DCS (ß = 0.242; P = .008) and ΔDCS-PCS (ß = 0.295; P < .001) are independent predictors of PWD. Performing the multivariate analysis for arrhythmic substrates, it is observed that only ΔDCS-PCS continued to be an independent predictor of PWD. Analysis of the receiver operating characteristic curves showed that regardless of the types of arrhythmic substrates, PWD discriminates significantly, but moderately, to patients with P-DCS and ΔDCS-PCS ≥75 percentile. CONCLUSIONS: Interatrial and intraleft atrial conduction times were directly and significantly correlated with PWD, but only weakly, and were independent predictors of PWD. In general, PWD correctly discriminates patients with high values in interatrial and intraleft atrial conduction times, but moderately. This is maintained in cases with accessory pathways; however, in patients with AVNRT it only does so for intraleft atrial conduction times. Interatrial and intraleft atrial conduction times weakly explains PWD.

Duración de la onda P en las 12 derivaciones del electrocardiograma y su relación con el tiempo de conducción interauricular en pacientes con taquicardias paroxísticas supraventriculares / P wave duration in the 12 leads of the electrocardiogram and its relationship with interatrial conduction time in patients with paroxysmal supraventricular tachycardias

RESUMEN Introducción: Existen algunos estudios que relacionan parámetros de la onda P con diferentes tiempos de conducción auricular, pero no se han realizado teniendo en cuenta a cada derivación del electrocardiograma. Objetivo: Determinar la duración de la onda P (Pdur) en las 12 derivaciones y relacionarlas con el tiempo de conducción interauricular. Método: Estudio de corte transversal en 153 pacientes adultos con diagnóstico confirmado de taquicardia por reentrada intranodal (TRIN) o vías accesorias mediante estudio electrofisiológico invasivo. Resultados: Al comparar la Pdur entre sustratos arrítmicos por cada derivación, no existieron diferencias significativas, excepto en V6. En las derivaciones DII, DIII, aVR, aVF, V1 y de V3-V6 la Pdur se correlacionó con el tiempo de conducción interauricular en ambos sustratos arrítmicos. En el análisis multivariado, la Pdur constituyó un predictor independiente de tiempos de conducción interauricular ≥ 95 percentil, en las derivaciones de cara inferior y en V3, V5 y V6. Se observaron altos valores del área bajo la curva de la Característica Operativa del Receptor en las derivaciones DII (0,950; p<0,001), DIII (0,850; p<0,001) y V5 (0,891; p<0,001). Conclusiones: No existen diferencias por derivación en la Pdur al comparar casos con TRIN y vías accesorias, excepto en V6. La mayoría de las derivaciones se correlacionaron con el tiempo de conducción interauricular. La Pdur fue un predictor independiente de tiempos de conducción interauricular ≥ 95 percentil. La derivación DII presenta la mayor capacidad discriminativa para encontrar valores prolongados del tiempo de conducción interauricular.

ABSTRACT Introduction: Although some studies relate P wave parameters to different atrial conduction times, they do not consider each electrocardiogram lead separately. Objective: To determine the duration of P wave (Pdur) in the 12 leads of the electrocardiogram and relate it to the interatrial conduction time. Method: We conducted a cross-sectional study in 153 adult patients with confirmed diagnosis of atrioventricular nodal reentry tachycardia (AVNRT) or accessory pathways by invasive electrophysiological study. Results: When comparing the Pdur between arrhythmic substrates by each lead, no significant differences were found, except for V6. In leads II, III, aVR, aVF, V1 and V3-V6, Pdur was correlated with the interatrial conduction time in both arrhythmic substrates. In our multivariate analysis, the Pdur was an independent predictor of interatrial conduction times ≥ 95 percentile in inferior wall leads and in V3, V5 and V6. High values of the area under the receiver operating characteristic curve were observed in II (0.950; p<0.001), III (0.850; p<0.001) and V5 (0.891; p<0.001) leads. Conclusions: The Pdur showed no difference by leads when comparing cases with AVNRT and accessory pathways, except for V6. Most of the leads were correlated with the interatrial conduction time; Pdur was an independent predictor of interatrial conduction times ≥ 95 percentile. Lead II has the greatest discriminatory ability to find prolonged values of interatrial conduction time.

PET-CT: Signos radiológicos en el Síndrome Sarcoidosis-Linfoma: Reporte de un caso y revisión / PET-CT: Radiologic signs in Sarcoidosis-Lymphoma Syndrome: Case Reporte and review

El síndrome sarcoidosis-linfoma es una entidad clínica a la cual se puede llegar de distintas formas a su diagnóstico. Algunas de las mismas suelen ser atípicas. Para estos casos complejos, la tomografía por emisión de positrones (PET) combinado con un escáner de tomografía computarizada de rayos X (CT), (PET-CT) es definitorio para llegar posteriormente a la biopsia. Se presenta un caso clínico de nuestro grupo que da lugar a la revisión/puesta al día correspondiente.

Sarcoidosis-lymphoma syndrome is a clinical entity that can be diagnosed in different ways. Some of them are atypical. For these complex cases, positron emission tomography (PET) combined with an X-ray computed tomography (CT) scanner (PET-CT) is definitive for subsequent biopsy. A clinical case of our group is presented, which leads to the corresponding revision/update.

Mapeo y ablación exitosa, desde el interior de la vena cardíaca magna, de extrasístoles ventriculares originados en el techo (summit) del ventrículo izquierdo / Mapping and successful ablation, from within the great cardiac vein, of premature ventricular contractions originating from the summit of the left ventricle

RESUMEN Se presenta el caso de una paciente de 43 años, con antecedentes de salud aparente, hasta varias semanas previas a su ingreso, cuando comenzó a presentar síncopes precedidos de palpitaciones. Se realizó estudio electrofisiológico y se demostró precocidad en la porción distal del electrodo de registro de seno coronario, que corresponde a la vena cardíaca magna (interventricular anterior) y techo (summit) del ventrículo izquierdo. A pesar del excelente registro precoz se estudiaron estructuras vecinas como el tracto de salida del ventrículo izquierdo en la cúspide coronaria izquierda, aquí el mapeo eléctrico (pace mapping) no fue concordante total. En el sitio de la precocidad obtenida dentro del sistema venoso cardíaco se realizó mapeo concordante 100%, con una precocidad del catéter de ablación de -30 milisegundos. Se decidió ablación con incrementos progresivos de temperatura y potencia con corte de impedancia (termomapping) y se logró el éxito de la ablación sin reproducibilidad de la arritmia y excelente evolución posterior.

ABSTRACT The case of a 43-year-old female patient is presented, with an apparent history of good health, up to several weeks prior to admission, when she began to present syncopes preceded by palpitations. An electrophysiological study was performed and prematurity in the distal portion of the coronary sinus recording electrode was demonstrated, which corresponds to the great cardiac vein (anterior interventricular vein) and summit of the left ventricle. Despite the excellent early registration, neighboring structures were studied, such as the left ventricular outflow tract in the left coronary cusp, here the pace mapping was not totally concordant. At the site of the precocity obtained within the cardiac venous system, a 100% concordant mapping was achieved, with an ablation catheter's precocity of -30 milliseconds. The ablation was decided with progressive increases in temperature and power with thermomapping and the success of the ablation was achieved without reproducibility of the arrhythmia and excellent subsequent evolution.