Treatment patterns and persistence on disease modifying therapies for multiple sclerosis and its associated factors.

BACKGROUND: Effective interventions for Multiple Sclerosis require timely treatment optimization which usually involves switching disease modifying therapies. The patterns of prescription and the reasons for changing treatment in people with MS, especially in low prevalence populations, are unknown. OBJECTIVES: To describe the persistence, reasons of DMT switches and prescription patterns in a cohort of Colombian people with MS. METHODS: We conducted a retrospective observational study including patients with confirmed MS with at least one visit at our centre. We estimated the overall incidence rate of medication changes and assessed the persistence on medication with Kaplan-Meier survival estimates for individual medications and according to efficacy and mode of administration. The factors associated with changing medications were assessed using adjusted Cox proportional-hazards models. The reasons for switching medication changes were described, and the prescription patterns were assessed using network analysis, with measures of centrality. RESULTS: Seven hundred one patients with MS were included. Mean age was 44.3 years, and 67.9% were female. Mean disease duration was 11.3 years and 84.5% had relapsing MS at onset, with median EDSS of 1.0. Treatment was started in 659 (94%) of the patients after a mean of 3 years after MS symptom onset. Among them, 39.5% maintained their initial DMT, 29.9% experienced a single DMT change, while 18.7% went through two, and 11.9% had three or more DMT changes until the final follow-up. The total number of treatment modifications reached 720, resulting in an incidence rate of 1.09 (95% confidence interval: 1.01-1.17) per patient per year The median time to change after the first DMT was 3.75 years, and was not different according to the mode of administration or efficacy classification. The main reasons for changing DMT were MS activity (relapses, 56.7%; MRI activity, 18.6%), followed by non-serious adverse events (15.3%) and disability (11.1%). Younger age at MS onset, care under our centre and insurer status were the main determinants of treatment change. Network analysis showed that interferons and fingolimod were the most influential DMTs. CONCLUSIONS: A majority of patients switch medications, mostly due to disease activity, and in association with age and insurer status.

The Mediterranean Mussel Mytilus galloprovincialis (Mollusca: Bivalvia) in Chile: Distribution and Genetic Structure of a Recently Introduced Invasive Marine Species.

The genetic characteristics of invasive species have a significant impact on their ability to establish and spread. The blue mussel (Mytilus galloprovincialis), native to the Mediterranean Sea, is a leading invasive species of intertidal coasts throughout much of the world. Here, we used mitochondrial DNA sequence data to investigate the genetic diversity and phylogeographic structure of invasive (M. galloprovincialis) versus native (Mytilus chilensis) populations of blue mussels in Chile. We evaluated whether genetic diversity in invasive populations could be explained by the genetic characteristics of the native sources from which they might be derived. A phylogenetic analysis confirmed two lineages of the invasive M. galloprovincialis, i.e., the NW Atlantic and the Mediterranean lineages. We found no evidence of genetic structure in the invasive range of M. galloprovincialis in Chile, most probably because of its recent arrival. We did, however, detect a spatial mixture of both M. galloprovincialis lineages at sampling locations along the Chilean coast, giving rise to higher levels of genetic diversity in some areas compared to the population of native M. chilensis. The coastal area of the invasion is still small in extent (~100 km on either side of two large ports), which supports the hypothesis of a recent introduction. Further expansion of the distribution range of M. galloprovincialis may be limited to the north by increasing water temperatures and to the south by a natural biogeographic break that may slow or perhaps stop its spread. The use of internal borders as a tool to minimise or prevent M. galloprovincialis spread is therefore a genuine management option in Chile but needs to be implemented rapidly.

New approaches to recovery after stroke.

After a stroke, several mechanisms of neural plasticity can be activated, which may lead to significant recovery. Rehabilitation therapies aim to restore surviving tissue over time and reorganize neural connections. With more patients surviving stroke with varying degrees of neurological impairment, new technologies have emerged as a promising option for better functional outcomes. This review explores restorative therapies based on brain-computer interfaces, robot-assisted and virtual reality, brain stimulation, and cell therapies. Brain-computer interfaces allow for the translation of brain signals into motor patterns. Robot-assisted and virtual reality therapies provide interactive interfaces that simulate real-life situations and physical support to compensate for lost motor function. Brain stimulation can modify the electrical activity of neurons in the affected cortex. Cell therapy may promote regeneration in damaged brain tissue. Taken together, these new approaches could substantially benefit specific deficits such as arm-motor control and cognitive impairment after stroke, and even the chronic phase of recovery, where traditional rehabilitation methods may be limited, and the window for repair is narrow.

Chromosome-Level Genome Assembly of the Blue Mussel Mytilus chilensis Reveals Molecular Signatures Facing the Marine Environment.

The blue mussel Mytilus chilensis is an endemic and key socioeconomic species inhabiting the southern coast of Chile. This bivalve species supports a booming aquaculture industry, which entirely relies on artificially collected seeds from natural beds that are translocated to diverse physical-chemical ocean farming conditions. Furthermore, mussel production is threatened by a broad range of microorganisms, pollution, and environmental stressors that eventually impact its survival and growth. Herein, understanding the genomic basis of the local adaption is pivotal to developing sustainable shellfish aquaculture. We present a high-quality reference genome of M. chilensis, which is the first chromosome-level genome for a Mytilidae member in South America. The assembled genome size was 1.93 Gb, with a contig N50 of 134 Mb. Through Hi-C proximity ligation, 11,868 contigs were clustered, ordered, and assembled into 14 chromosomes in congruence with the karyological evidence. The M. chilensis genome comprises 34,530 genes and 4795 non-coding RNAs. A total of 57% of the genome contains repetitive sequences with predominancy of LTR-retrotransposons and unknown elements. Comparative genome analysis of M. chilensis and M. coruscus was conducted, revealing genic rearrangements distributed into the whole genome. Notably, transposable Steamer-like elements associated with horizontal transmissible cancer were explored in reference genomes, suggesting putative relationships at the chromosome level in Bivalvia. Genome expression analysis was also conducted, showing putative genomic differences between two ecologically different mussel populations. The evidence suggests that local genome adaptation and physiological plasticity can be analyzed to develop sustainable mussel production. The genome of M. chilensis provides pivotal molecular knowledge for the Mytilus complex.

Predictors of use of direct oral anticoagulants in patients with venous thromboembolism: Findings from the Registro Informatizado Enfermedad Tromboembólica registry.

Background: Current guidelines recommend the use of direct oral anticoagulants (DOACs) for patients with venous thromboembolism (VTE). However little is known about the use of DOACs in daily practice. Methods: We used the RIETE registry to identify predictors of use of DOACs for initial and/or long-term therapy of VTE based on patient-related factors, institution-related factors or over time. Results: Among 41,678 patients from March 2013 to September 2021, 12,286 (29%) used DOACs: for initial therapy 6,456; for long-term therapy 12,046. On multivariable analysis, independent predictors were: age < 65 years (odds ratio [OR]: 1.30; 95% CI: 1.23-1.38), body weight <50 kg (OR: 0.54; 95% CI: 0.45-0.65) or >120 kg (OR: 0.64; 95% CI: 0.53-0.77), initial VTE presentation as pulmonary embolism (OR: 1.18; 95% CI: 1.13-1.25), recent bleeding (OR: 0.53; 95% CI: 0.45-0.63), renal insufficiency (OR: 0.44; 95% CI: 0.38-0.51), liver cirrhosis (OR: 0.32; 95% CI: 0.20-0.52), thrombocytopenia (OR: 0.40; 95% CI: 0.34-0.49), atrial fibrillation (OR: 1.58; 95% CI: 1.42-1.75) and prior VTE (OR: 1.14; 95% CI: 1.06-1.22). The DOACs were more likely used in other European countries (OR: 8.97; 95% CI: 8.49-9.49), America (OR: 6.35; 95% CI: 5.67-7.11) or in other countries of the world (OR: 2.99; 95% CI: 2.70-3.31) than in Spain, and progressively increased from 2013-2015 to 2016-2018 (OR: 2.78; 95% CI: 2.62-2.95) and 2019-2021 (OR: 6.36; 95% CI: 5.95-6.80). Conclusion: In this large multinational VTE registry, variations were observed in the use of DOACs according to patient or country factors, and over time. The safety, costs, and influence of the DOACs on VTE-related outcomes in daily practice warrant further investigation.

Proximal and fatty acid analysis in Ostrea chilensis, Crassostrea gigas and Mytilus chilensis (Bivalvia: Mollusca) from southern Chile.

Oysters and blue mussels are important hydrobiological resources for aquaculture. In Chile, they are farming on the Chiloé island, where around 18% of the world's mussels are produced, however, their nutritional dynamics are largely unknown. For this reason, the objective of this study was to determine the proximal biochemical composition and the fatty acid profile in the Chilean oyster (Ostrea chilensis), the Pacific oyster (Crassostrea gigas) and the Chilean mussel (Mytilus chilensis), to perform an intra and interspecific comparison. Shellfish sampled in winter were characterized by a high protein content, followed by medium values for lipid content and a low carbohydrate content compared to similar species in Europe. Also, oysters and mussels were found to be rich in omega-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA), so they can be considered excellent functional food option for a healthy human diet. Their high contribution of n-3 LC-PUFA ranged between 5.2-12.9 µg FA mg-1 dry weight with high n-3/n-6 ratios, which depends on both the species and the on-growing location. Both taxa can be considered a plausible option to promote a healthy diet of marine origin in future generations. Also, these results could benefit the projection and development of aquaculture of these mollusks.

Feeding response and dynamic of intoxication and detoxification in two populations of the flat oyster Ostrea chilensis exposed to paralytic shellfish toxins (PST).

Juvenile oysters (Ostrea chilensis) from two populations (Quempillén estuary and Pullinque bay) were exposed to a toxic diet containing paralytic shellfish toxins (PST), produced by Alexandrium catenella, followed by a detoxification period. Feeding behaviour, toxin profile, dynamics of intoxication/detoxification, and survival were evaluated over the entire experimental period. Both populations reduced their feeding rates during the 30-day exposure to the toxic diet. This negative effect was reversible when the diet was switched to the non-toxic one. Oysters from the estuary accumulated PST more rapidly than the population from the bay, suggesting their increased ability to cope with more adverse conditions. Both populations showed low detoxification capacity. Survival was significantly higher in oysters from the estuary, compared to those from the bay. Due to the increasing frequency and intensity of A. catenella blooms in southern Chile, it is necessary to better understand the responses of O. chilensis in different environments. This is important not only because of the ecological and commercial relevance of the bivalve, but also in consideration of expected climate change scenarios, where the new environmental conditions could favour the frequency and intensity of harmful algal bloom events.

Genetic structure and diversity of the Chilean flat oyster Ostrea chilensis (Bivalvia: Ostreidae) along its natural distribution from natural beds subject to different fishing histories.

Ostrea chilensis (Küster, 1844), the flat oyster, is native to Chile and New Zealand. In Chile, it occurs in a few natural beds, from the northern part of Chiloé Island (41 ºS) to the Guaitecas Archipelago (45 ºS). This bivalve is slow growing, broods its young, and has very limited dispersal potential. The Ostrea chilensis fishery has been over-exploited for a number of decades such that in some locations oysters no longer exist. The aim of this study was to study the genetic diversity of the Chilean flat oyster along its natural distribution to quantify the possible impact of the dredge fishery on wild populations. The genetic structure and diversity of Ostrea chilensis from six natural beds with different histories of fishing activity were estimated. Based on mitochondrial (Cytb) and nuclear (ITS1) DNA sequence variation, our results provide evidence that genetic diversity is different among populations with recent history of wild dredge fishery efforts. We discuss the possible causes of these results. Ultimately, such new information may be used to develop and apply new management measures to promote the sustainable use of this valuable marine resource.

Imaging modalities for confirming pulmonary embolism during pregnancy: results from a multicenter international study.

OBJECTIVES: We explored the variations in use of imaging modalities for confirming pulmonary embolism (PE) according to the trimester of pregnancy. METHODS: We included all pregnant patients with confirmed acute PE from RIETE, a prospective registry of patients with PE (03/2001-02/2020). Imaging modalities included computed tomography pulmonary angiography (CTPA), ventilation-perfusion (V/Q) scan, or presence of signs of acute PE along with imaging-confirmed proximal deep vein thrombosis (pDVT) without pulmonary vascular imaging. We compared the imaging modalities to postpartum patients with PE, and other non-pregnant women with PE. RESULTS: There were 157 pregnant patients (age: 32.7 ± 0.5), 228 postpartum patients (age: 33.9 ± 0.5), and 23,937 non-pregnant non-postpartum women (age: 69.5 ± 0.1). CTPA was the most common modality for confirming PE, from 55.7% in first trimester to 58.3% in second trimester, and 70.0% in third trimester. From first trimester to third trimester, V/Q scanning was used in 21.3%, 16.7%, and 18.3% of cases, respectively. Confirmed pDVT along with the presence of signs/symptoms of PE was the confirmatory modality for PE in 21.3% of patients in first trimester, 19.4% in second trimester, and 6.7% in third trimester. The proportion of postpartum patients confirmed with CTPA (85.5%) was comparable to that of non-pregnant non-postpartum women (83.2%). From the first trimester of pregnancy to postpartum period, there was a linear increase in the proportion of patients with PE diagnosed with CTPA (p = 0.039). CONCLUSION: CTPA was the primary modality for confirming PE in all trimesters of pregnancy, although its proportional use was higher in later stages of pregnancy. KEY POINTS: • Computed tomography pulmonary angiography (CTPA) was the primary modality of diagnosis in all trimesters of pregnancy among patients with confirmed pulmonary embolism, even in the first trimester. • From the first trimester of pregnancy to postpartum period, there was a linear increase in the proportion of patients with pulmonary embolism who were diagnosed based on CTPA. • In the postpartum period, use of CTPA as the modality to confirm pulmonary embolism was comparable to non-pregnant patients.

Blue mussels of the Mytilus edulis species complex from South America: The application of species delimitation models to DNA sequence variation.

Smooth-shelled blue mussels, Mytilus spp., have a worldwide antitropical distribution and are ecologically and economically important. Mussels of the Mytilus edulis species complex have been the focus of numerous taxonomic and biogeographical studies, in particular in the Northern hemisphere, but the taxonomic classification of mussels from South America remains unclear. The present study analysed 348 mussels from 20 sites in Argentina, Chile, Uruguay and the Falkland Islands on the Atlantic and Pacific coasts of South America. We sequenced two mitochondrial locus, Cytochrome c Oxidase subunit I (625 bp) and 16S rDNA (443 bp), and one nuclear gene, ribosomal 18S rDNA (1770 bp). Mitochondrial and nuclear loci were analysed separately and in combination using maximum likelihood and Bayesian inference methods to identify the combination of the most informative dataset and model. Species delimitation using five different models (GMYC single, bGMYC, PTP, bPTP and BPP) revealed that the Mytilus edulis complex in South America is represented by three species: native M. chilensis, M. edulis, and introduced Northern Hemisphere M. galloprovincialis. However, all models failed to delimit the putative species Mytilus platensis. In contrast, however, broad spatial scale genetic structure in South America using Geneland software to analyse COI sequence variation revealed a group of native mussels (putatively M. platensis) in central Argentina and the Falkland Islands. We discuss the scope of species delimitation methods and the use of nuclear and mitochondrial genetic data to the recognition of species within the Mytilus edulis complex at regional and global scales.

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism.

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.

[SARS-CoV-2 infection and ischemic stroke]. / Infección por SARS-CoV-2 y ataque cerebrovascular isquémico.

The new coronavirus SARS-CoV-2 is causing a huge impact on health, economy, and social dynamics. The world is facing an emerging viral disease for which no specific treatment is available, and many aspects of the clinical behavior of the disease are still unknown, which makes the diagnosis and management a big challenge. Various neurological manifestations have been described and associated with SARS-CoV-2 infection. Stroke occurs in up to 6% of all patients with COVID-19, a figure that becomes significant given the large number of patients diagnosed to date. The clinical characteristics, presentation, evolution, and prognosis of these patients seem to have peculiarities that have not been seen in previous forms of stroke. Every time younger patients are observed, without a medical history, without infectious symptoms, with serious neurological results that pose a challenging and difficult approach. This review synthesizes the information available on the clinical characteristics and the proposals for its management.

Comparative clinical prognosis of massive and non-massive pulmonary embolism: A registry-based cohort study.

AIMS: Little is known about the prognosis of patients with massive pulmonary embolism (PE) and its risk of recurrent venous thromboembolism (VTE) compared with non-massive PE, which may inform clinical decisions. Our aim was to compare the risk of recurrent VTE, bleeding, and mortality after massive and non-massive PE during anticoagulation and after its discontinuation. METHODS AND RESULTS: We included all participants in the RIETE registry who suffered a symptomatic, objectively confirmed segmental or more central PE. Massive PE was defined by a systolic hypotension at clinical presentation (<90 mm Hg). We compared the risks of recurrent VTE, major bleeding, and mortality using time-to-event multivariable competing risk modeling. There were 3.5% of massive PE among 38 996 patients with PE. During the anticoagulation period, massive PE was associated with a greater risk of major bleeding (subhazard ratio [sHR] 1.72, 95% confidence interval [CI] 1.28-2.32), but not of recurrent VTE (sHR 1.15, 95% CI 0.75-1.74) than non-massive PE. An increased risk of mortality was only observed in the first month after PE. After discontinuation of anticoagulation, among 11 579 patients, massive PE and non-massive PE had similar risks of mortality, bleeding, and recurrent VTE (sHR 0.85, 95% CI 0.51-1.40), but with different case fatality of recurrent PE (11.1% versus 2.4%, P = .03) and possibly different risk of recurrent fatal PE (sHR 3.65, 95% CI 0.82-16.24). CONCLUSION: In this large prospective registry, the baseline hemodynamic status of the incident PE did not influence the risk of recurrent VTE, during and after the anticoagulation periods, but was possibly associated with recurrent PE of greater severity.

Impacto del COVID-19 en la salud mental: revisión de la literatura / Impact of COVID-19 on mental health: a literature reviewa literature review

Introducción: el 12 de diciembre de 2019 en Wuhan, China, se reportó el primer caso de COVID-19, que después se extendió y alcanzó la categoría de pandemia mundial, obligando a los gobiernos a tomar medidas de salud pública urgentes; lo que ha implicado la aparición o complicación de los problemas de salud mental en la población. Objetivo: describir el impacto del COVID-19 en la salud mental a partir de la revisión de la literatura científica. Materiales y métodos: se revisó la literatura consultando 9 bases de datos con los términos de búsqueda "COVID-19" y "mental" y el operador booleano "AND". Los artículos fueron revisados y sintetizados con la ayuda de una matriz de 5 pasos y evaluados con las pruebas STROBE y CASPe. Un total de 43 artículos fueron seleccionados. Resultados: se encontró que China con 21 estudios (46,7%) presentó la mayor producción, utilizando diversos tipos de instrumentos aplicados de modo remoto. Las muestras fueron tomadas en momentos diferentes del brote (fase inicial, pico de brote y después del pico), desde diciembre 2019 hasta abril de 2020, en especial con diseños transversales (90.7%). El impacto psicológico se agrupó en las categorías de afectos negativos, afectos positivos, pensamientos negativos, ansiedad, depresión, estrés, alteraciones del comportamiento, consumo de sustancias psicoactivas, síntomas fisiológicos, alteraciones del sueño, impacto psicológico y cambios positivos en el bienestar. Conclusiones: se evidenciaron impactos del brote del COVID-19 en la salud mental. No se hallaron estudios colombianos.

Introduction: the first case of COVID-19 was reported in Wuhan, China on December 12 2019, the disease spread rapidly becoming a global pandemic; governments were forced to take urgent public health measures; causing the development or complication of psychological issues in the general population. Objective: to describe the impact of COVID-19 on mental health based on a review of the scientific literature. Materials and Methods: the literature review consisted of a search in nine databases using the terms "COVID-19" and "mental" and Boolean operator "AND". Articles were reviewed and synthetized based on a 5-step matrix and evaluated using the STROBE and CASPe scales. A total of 43 articles were selected. Results: the highest number of studies (21- 46.7%) was found in China, using diverse types of remotely applied instruments. Samples were taken at different times of the outbreak (initial stage, outbreak peak and post-peak), from December 2019 to April 2020, relying mostly on cross-sectional studies (90.7%). The psychological impact was grouped in the following categories: negative affect, positive affect, negative thoughts, anxiety, depression, stress, behavioral alterations, use of psychoactive substances, physiologic symptoms, sleep disturbances, psychological impact and positive changes in wellbeing. Conclusions: various impacts of the COVID-19 outbreak on mental health were evidenced. No studies on this matter were found in Colombia.

The genomic and epigenomic evolutionary history of papillary renal cell carcinomas.

Intratumor heterogeneity (ITH) and tumor evolution have been well described for clear cell renal cell carcinomas (ccRCC), but they are less studied for other kidney cancer subtypes. Here we investigate ITH and clonal evolution of papillary renal cell carcinoma (pRCC) and rarer kidney cancer subtypes, integrating whole-genome sequencing and DNA methylation data. In 29 tumors, up to 10 samples from the center to the periphery of each tumor, and metastatic samples in 2 cases, enable phylogenetic analysis of spatial features of clonal expansion, which shows congruent patterns of genomic and epigenomic evolution. In contrast to previous studies of ccRCC, in pRCC, driver gene mutations and most arm-level somatic copy number alterations (SCNAs) are clonal. These findings suggest that a single biopsy would be sufficient to identify the important genetic drivers and that targeting large-scale SCNAs may improve pRCC treatment, which is currently poor. While type 1 pRCC displays near absence of structural variants (SVs), the more aggressive type 2 pRCC and the rarer subtypes have numerous SVs, which should be pursued for prognostic significance.

Outcomes after venous thromboembolism in patients with gastric cancer: Analysis of the RIETE Registry.

Gastric cancer is the fifth most common malignancy worldwide. Venous thromboembolism is an independent predictor of death among patients with gastric cancer. We aimed to describe the factors associated with mortality, thrombosis recurrence, and bleeding complications in patients with gastric cancer who develop venous thromboembolism. We included 612 patients with gastric cancer and venous thromboembolism in the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry from 2001 to 2018. We used Cox proportional hazard ratios and a Fine-Gray model to define factors associated with outcomes. The overall mortality at 6 months was 44.4%. Factors associated with increased 6-month mortality included immobility (HR 1.8, 95% CI 1.3-2.4; p < 0.001), anemia (HR 1.4, 95% CI 1.1-1.8; p < 0.02), and leukocytosis (HR 1.8, 95% CI 1.4-2.3; p < 0.001). Recurrent thrombosis occurred in 6.5% of patients and major bleeding complications in 8.5% of the cohort. Male sex was the main factor associated with thrombosis recurrence (HR 2.1, 95% CI 1.1-4.0; p < 0.02) and hemoglobin below 10 g/dL (HR 1.6, 95% CI 1.05-2.50; p = 0.03) the main factor associated with bleeding. In conclusion, patients with gastric cancer who develop venous thrombosis have a very high likelihood of death. Low hemoglobin in this population is associated with poor outcomes.

Natural history of patients with venous thromboembolism and hereditary hemorrhagic telangiectasia. Findings from the RIETE registry.

BACKGROUND: Limited data exist about the clinical presentation, ideal therapy and outcomes of patients with hereditary hemorrhagic telangiectasia (HHT) who develop venous thromboembolism (VTE). METHODS: We used the data in the RIETE Registry to assess the clinical characteristics, therapeutic approaches and clinical outcomes during the course of anticoagulant therapy in patients with HHT according to initial presentation as pulmonary embolism (PE) or deep venous thrombosis (DVT). RESULTS: Of 51,375 patients with acute VTE enrolled in RIETE from February 2009 to January 2019, 23 (0.04%) had HHT: 14 (61%) initially presented with PE and 9 (39%) with DVT alone. Almost half (47.8%) of the patients with VTE had a risk factor for VTE. Most PE and DVT patients received low-molecular-weight heparin for initial (71 and 100%, respectively) and long-term therapy (54 and 67%, respectively). During anticoagulation for VTE, the rate of bleeding events (major 2, non-major 6) far outweighed the rate of VTE recurrences (recurrent DVT 1): 50.1 bleeds per 100 patient-years (95%CI: 21.6-98.7) vs. 6.26 recurrences (95%CI: 0.31-30.9; p = 0.020). One major and three non-major bleeding were epistaxis. No patient died of bleeding. One patient died shortly after being diagnosed with acute PE. CONCLUSIONS: During anticoagulation for VTE in HHT patients, there were more bleeding events than VTE recurrences. Most bleeding episodes were non-major epistaxis.

Frequency and prognostic impact of acute kidney injury in patients with acute pulmonary embolism. Data from the RIETE registry.

RATIONALE: Acute kidney injury (AKI) is associated with a poor outcome. Although pulmonary embolism (PE) may promote AKI through renal congestion and/or hemodynamic instability, its frequency and influence on outcome in patients with acute PE have been poorly studied. METHODS: The frequency of AKI (defined according to the "Kidney Disease: Improving Global Outcomes" definition) at baseline and its influence on the 30-day mortality was evaluated in patients with acute PE from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. We used multivariate analysis to assess whether the presence of AKI influenced the risk for 30-day death. RESULTS: The study included 21,131 patients, of whom 6222 (29.5%) had AKI at baseline: 4385 patients (21%) in stage 1, 1385 (6.5%) in stage 2 and 452 (2%) in stage 3. The proportion of patients with high-risk PE in those with no AKI, AKI stage 1, AKI stage 2 or AKI stage 3 was: 2.8%, 5.3%, 8.8% and 12%, respectively (p < 0.001). After 30 days, 1236 patients (5.9%) died. Overall mortality was 4% in patients with no AKI, 8.4% in AKI stage 1, 14% in AKI stage 2 and 17% in AKI stage 3 (all p < 0.001). AKI was independently associated with an increased risk of all-cause death at 30 days (odds ratio = 1.25; 95%CI: 1.02-1.54). CONCLUSIONS: One in every 3-4 patients with acute PE had AKI at baseline. The presence of AKI independently predicted 30-day mortality. This study suggests that AKI may deserve to be evaluated as a prognostic factor in patients with acute PE.

The association between dengue immunoglobulin G titres with previous clinical dengue infection and white cell counts in Cuban children: A population-based study.

BACKGROUND: The prevalence of dengue infection is increasing globally. There are few prospective population-based surveillance studies of the immunological and inflammatory consequences of exposure to dengue virus in young children. OBJECTIVE: To study the association between serologically confirmed prior medical diagnosis of dengue infection and blood measures of systemic inflammation with dengue virus immunoglobulin G levels. METHODS: A population-based study of healthy three-year old children living in Havana, Cuba. RESULTS: 865 individuals provided a blood sample. Fourteen (1.6%) had a prior medical diagnosis of dengue infection, and 851 individuals had no prior medical diagnosis. There was no difference in the serum immunoglobulin G titres between these groups (Mann-Whitney test, p = 0.49). Total white cell count, blood neutrophil and eosinophil counts were linearly associated with a dengue immunoglobulin G value above the median value. CONCLUSIONS: There was no difference between the dengue immunoglobulin G titres in young children who had previously had clinically proven dengue infection compared to those who had no diagnosis of prior infection. This may be a consequence of a relatively high prevalence of sub-clinical infection. A higher dengue immunoglobulin G level was positively associated with a range of inflammatory biomarkers, although these data cannot demonstrate a causal association.