Comparative study between two European inception cohorts of patients with early systemic lupus erythematosus.

OBJECTIVES: To compare the main characteristics of two inception cohorts (Italian [ITC] and Spanish [SPC]) cohorts of patients with systemic lupus erythematosus (SLE) at the time of diagnosis and at one year of follow-up. METHODS: Demographic, clinical and immunological characteristics, and treatments at SLE diagnosis and at 12 months of follow-up of ITC and SPC were compared. RESULTS: One hundred and sixty-four patients in the ITC and 231 patients in the SPC were compared. the patients from ITC were younger at SLE diagnosis (41.1±15.0 years vs. 46.4±15.6 years; p<0.001) and had a higher prevalence of arthritis (62.8% vs. 45.5%; p=0.001), serositis (25.6% vs. 16.0%; p=0.026), neurological involvement (7.9% vs. 1.7%; p=0.006), and immunological abnormalities (anti-dsDNA, anti-Sm, antiphospholipid antibodies) (93.9% vs. 77.8%; p<0.001). Conversely, photosensitivity (29.5% in ITC vs. 45.9% in SPC; p=0.001) and oral ulcers (12.4% vs. 30.3%; p<0.001) were more frequent at onset of SLE in the Spanish patients. At the first 12 months of follow-up, these differences were maintained. At SLE onset, more Italian patients received glucocorticoids (85.4% vs. 50.2%; p<0.001) and immunosuppressive agents. At 12 months of follow-up, more Spanish patients were treated with antimalarials (75.6% in ITC vs. 90.0% in SPC; p<0.001). Conversely, the use of glucocorticoids was lower in SPC (89.0% in ITC vs. 57.1% in SPC; p<0.001). CONCLUSIONS: These cohorts presented different profiles in terms of pattern of organ/system involvement and disease treatment, possibly as a consequence of patient selection or different disease management approaches between Italy and Spain.

Patterns of drug therapy in newly diagnosed Spanish patients with systemic lupus erythematosus.

OBJECTIVES: This is the first Spanish multicentric inception lupus cohort, formed by SLE patients attending Spanish Internal Medicine Services since January 2009. We aimed to analyse drug therapy during the first year of follow-up according to disease severity. METHODS: 223 patients who had at least one year of follow-up were enrolled upon diagnosis of SLE. Therapy with prednisone, pulse methyl-prednisolone, hydroxychloroquine, immunosuppressives and calcium/vitamin D was analysed. RESULTS: Prednisone was given to 65% patients, at a mean (SD) daily dose of 11 (10) mg/d. 38% patients received average doses >7.5 mg/d during the first year. Patients with nephritis and with a SLEDAI ≥6 were treated with higher doses of prednisone. 81% of patients were treated with hydroxychloroquine, with higher frequency among those with a SLEDAI ≥6 (88% vs. 68%, p<0.001). The use of immunosuppressive drugs and methyl-prednisolone pulses was higher in patients with a baseline SLEDAI ≥6, however, differences were no longer significant when patients with lupus nephritis were excluded. The use of calcium/vitamin D increased with the dose of prednisone, however, 43% of patients on medium-high doses of prednisone did not take any calcium or vitamin D. CONCLUSIONS: This study gives a real-world view of the current therapeutic approach to early lupus in Spain. The generalised use of hydroxychloroquine is well consolidated. There is still a tendency to use prednisone at medium to high doses. Pulse methyl-prednisolone and immunosuppressive drugs were used in more severe cases, but not as steroid sparing agents. Vitamin D use was suboptimal.

PTPN22 is not associated with Behçet's disease. Study spanning the complete gene region in the Spanish population and meta-analysis of the functional variant R620W.

OBJECTIVES: The functional variant R620W of the protein tyrosine phosphatase non receptor-22 (PTPN22) gene plays an important role in susceptibility to several immuno-mediated pathologies. Behçet's disease (BD) is a complex disease related to the immune system with a demonstrated genetic base. The HLA class I genes are the most important genetic factors in BD although other genes are also involved in the susceptibility to this disease. The PTPN22 has been proposed as a candidate gene in BD but this association has not been clearly demonstrated yet. The aim of this study was to assess the association of PTPN22 with BD. METHODS: A cohort composed of 404 Spanish BD patients and 1517 unrelated healthy individuals ethnically matched was genotyped in rs2476601 (R620W). Five tag SNPs: rs1217412, rs2476599, rs3789607, rs3765598 and rs1217419 (spanning a 57 Kb region between 3'UTR and 5'UTR) and rs2488457 (located at the promoter region) were also studied in order to perform a screening of the complete gene. Genotyping was performed using TaqMan® assays. The rs2476601 data were included in a meta-analysis together with those published till the date. The rest of SNPs were used in a case-control study. RESULTS: No evidence of the association of rs2476601 with BD in the meta-analysis (P = 0.504 in the model of alleles) was found. In the case-control study, no statistically significant differences were observed when comparing the distribution of variants in patients and controls. CONCLUSIONS: Our results do not support a major role of the PTPN22 gene in BD.

Exploring the impact of Agaricus bisporus on mitigating lead reproductive toxicity using the Caenorhabditis elegans model.

Given that Agaricus bisporus, an edible mushroom, has demonstrated antioxidant properties, our investigation aimed to assess whether Agaricus bisporus could mitigate the toxic effects of lead (Pb) on Caenorhabditis elegans (C. elegans) model. A dose-response study was conducted involving Pb and Agaricus bisporus to determine appropriate doses. Subsequently, a co-exposure study utilizing C. elegans strains N2 and CL2166 was implemented, with groups designated as Control, Pb, Agaricus bisporus, and Pb + Agaricus bisporus. Our findings revealed that co-exposure to Pb + 100 mg/mL Agaricus bisporus resulted in reduced embryonic and larval lethality, increased brood size, and enhanced motility compared to nematodes exposed solely to Pb. Notably, our observations indicated a transfer of reproductive toxicity from nematode parents to their offspring. Thus, Agaricus bisporus may play a significant role in Pb detoxification, suggesting its potential as a natural antioxidant for neutralizing the detrimental effects of Pb on reproductive health.

QuantiFERON-TB reversion in children and adolescents with tuberculosis.

We analyzed 136 children with tuberculosis disease or infection and a positive QuantiFERON-TB (QFT) assay, followed-up for a median of 21 months (0.4-11years). QFT reversed in 16.9% of cases, with significant decreases in TB1 (-1.72 vs. -0.03 IU/ml, p=0.001) and TB2 (-1.65 vs. -0.43 IU/ml, p=0.005) levels compared to non-reverters. We found a higher QFT reversion rate among children under 5 years (25.0% vs 11.9%, p=0.042), and those with TST induration <15mm (29% vs 13.3%, p=0.055). Our data reveal that, although QFT test remained positive in the majority of children, reversion occurred in 16% of cases in a progressive and stable pattern. Younger age and reduced TST induration were associated with QFT reversion.

Photoaged polystyrene nanoplastics exposure results in reproductive toxicity due to oxidative damage in Caenorhabditis elegans.

The increase of plastic production together with the incipient reuse/recycling system has resulted in massive discards into the environment. This has facilitated the formation of micro- and nanoplastics (MNPs) which poses major risk for environmental health. Although some studies have investigated the effects of pristine MNPs on reproductive health, the effects of weathered MNPs have been poorly investigated. Here we show in Caenorhabditis elegans that exposure to photoaged polystyrene nanoplastics (PSNP-UV) results in worse reproductive performance than pristine PSNP (i.e., embryonic/larval lethality plus a decrease in the brood size, accompanied by a high number of unfertilized eggs), besides it affects size and locomotion behavior. Those effects were potentially generated by reactive products formed during UV-irradiation, since we found higher levels of reactive oxygen species and increased expression of GST-4 in worms exposed to PSNP-UV. Those results are supported by physical-chemical characterization analyses which indicate significant formation of oxidative degradation products from PSNP under UV-C irradiation. Our study also demonstrates that PSNP accumulate predominantly in the gastrointestinal tract of C. elegans (with no accumulation in the gonads), being completely eliminated at 96 h post-exposure. We complemented the toxicological analysis of PSNP/PSNP-UV by showing that the activation of the stress response via DAF-16 is dependent of the nanoplastics accumulation. Our data suggest that exposure to the wild PSNP, i.e., polystyrene nanoplastics more similar to those actually found in the environment, results in more important reprotoxic effects. This is associated with the presence of degradation products formed during UV-C irradiation and their interaction with biological targets.

Clinical impact of remote heart failure management using the multiparameter ICD HeartLogic alert.

INTRODUCTION AND OBJECTIVES: The multiparametric implantable cardioverter-defibrillator HeartLogic index has proven to be a sensitive and timely predictor of impending heart failure (HF) decompensation. We evaluated the impact of a standardized follow-up protocol implemented by nursing staff and based on remote management of alerts. METHODS: The algorithm was activated in HF patients at 19 Spanish centers. Transmitted data were analyzed remotely, and patients were contacted by telephone if alerts were issued. Clinical actions were implemented remotely or through outpatient visits. The primary endpoint consisted of HF hospitalizations or death. Secondary endpoints were HF outpatient visits. We compared the 12-month periods before and after the adoption of the protocol. RESULTS: We analyzed 392 patients (aged 69±10 years, 76% male, 50% ischemic cardiomyopathy) with implantable cardioverter-defibrillators (20%) or cardiac resynchronization therapy defibrillators (80%). The primary endpoint occurred 151 times in 86 (22%) patients during the 12 months before the adoption of the protocol, and 69 times in 45 (11%) patients (P<.001) during the 12 months after its adoption. The mean number of hospitalizations per patient was 0.39±0.89 pre- and 0.18±0.57 postadoption (P<.001). There were 185 outpatient visits for HF in 96 (24%) patients before adoption and 64 in 48 (12%) patients after adoption (P<.001). The mean number of visits per patient was 0.47±1.11 pre- and 0.16±0.51 postadoption (P<.001). CONCLUSIONS: A standardized follow-up protocol based on remote management of HeartLogic alerts enabled effective remote management of HF patients. After its adoption, we observed a significant reduction in HF hospitalizations and outpatient visits.

IL2/IL21 region polymorphism influences response to rituximab in systemic lupus erythematosus patients.

To determine whether the IL2/IL21 region, a general autoimmunity locus, contributes to the observed variation in response to rituximab in patients with systemic lupus erythematosus as well as to analyze its influence in a cohort including other autoimmune diseases. rs6822844 G/T polymorphism at the IL2-IL21 region was analyzed by TaqMan assay in 84 systemic lupus erythematosus (SLE) and 60 different systemic autoimmune diseases Spanish patients receiving rituximab. Six months after the first infusion patients were classified, according to the EULAR criteria, as good responders, partial responders and non-responders. A statistically significant difference was observed in GG genotype frequency between responder (total and partial response) (83.56%) and non-responder (45.45%) SLE patients (p=0.010, odds ratio (OR)=6.10 [1.28-29.06]). No association with the response was evident in the group of patients with autoimmune diseases other than lupus. Furthermore, when both groups of patients were pooled in a meta-analysis, a reduced statistical significance of the association was observed (p=0.024, OR=3.53 [1.06-11.64]). Our results show for a first time that IL2-IL21 region seems to play a role in the response to rituximab in SLE patients but not in other autoimmune diseases.

Repeat cryoablation as a redo procedure for atrial fibrillation ablation: Is it a good choice?

BACKGROUND: Ablation of atrial fibrillation (AF), both cryoablation ablation (CBA) and radiofrequency catheter ablation (RFCA), have demonstrated to be safe and effective. About 1 in 3 patients may face a redo due to recurrence and the best technique is unknown. The aim of this study is to assess the efficacy of CBA as a repeat procedure in patients with prior CBA or RFCA. METHODS: A nation-wide CBA registry (RECABA) was analyzed and patients were compared who had previously undergone CBA (Prior-CB) or RFCA (Prior-RF). The primary endpoint was AF recurrence at 12 months after a 3-month blanking period. A survival analysis was performed, univariate and multivariate Cox models were also built. RESULTS: Seventy-four patients were included. Thirty-three (44.6%) were in the Prior-CB group and 41 (55.4%) in the Prior-RF. There were more reconnected pulmonary veins in the Prior-RF than in Prior-CB group (40.4% vs.16.5%, p = 0.0001). The 12-month Kaplan-Meier estimate of freedom from AF recurrence after the blanking period was 61.0% (95% confidence interval [CI] 41.4-75.8%) in the Prior-CB, and 89.2% (95% CI 73.6-95.9%) in the Prior-RF group (p = 0.002). Multivariate Cox regression pointed Prior-CB as the sole independent predictor of AF recurrence, with an adjusted HR of 2.67 (95% CI 1.05-6.79). CONCLUSIONS: Repeat CBA shows higher rates of AF recurrences compared to CBA after a previous RFCA despite presenting less reconnected veins at the procedure. These data suggest that patients with AF recurrence after CBA may benefit from other ablation techniques after a recurrence. RECABA is registered at clinicaltrials.gov with the Unique Identifier NCT02785991.

Surveillance of Viral Respiratory Infections in the Neonatal Intensive Care Unit-Evolution in the Last 5 Years.

Viral respiratory infections (VRIs) in very low birthweight infants can be associated with high rates of morbidity. The COVID-19 pandemic has exerted a strong impact on viral circulation. The purpose of this study is to report on VRIs during NICU admission in infants below 32 weeks' gestation and compare data collected between the pre-and post-COVID-19 pandemic periods. A prospective surveillance study was conducted at a tertiary NICU between April 2016 and June 2022. The COVID-19 post-pandemic period was established as being from March 2020 onwards. Respiratory virus detection was performed by real-time multiplex PCR assays in nasopharyngeal aspirates (NPAs). A total of 366 infants were enrolled. There were no statistical differences between periods regarding infants' birth weight, gestational age, gender distribution, or rates of bronchopulmonary dysplasia. Among the 1589 NPA collected during the pre-COVID-19 period, 8.9% were positive, and among the 1147 NPA collected during the post-pandemic period, only 3% were positive (p < 0.005). The type of viruses detected did not differ according to the study period (pre-COVID19 vs. post-COVID-19): rhinovirus (49.5% vs. 37.5%), adenovirus (22.6% vs. 25%), and human coronavirus (12.9% vs. 16.7%). SARS-CoV-2 was only detected in one patient. In conclusion, the viral profile causing VRI during the pre-COVID-19 and post-COVID-19 era was similar. However, the total number of VRI dropped significantly, most probably due to the global increase in infection prevention measures.

Validity and Reliability of questionnaires measuring attitudes to oral health: A review of the literature.

Background: The instruments used to assess attitudes to oral health must be validated in order for their results to be reliable and comparable with other variables. The aim of this review was to analyze the ability of self-administered questionnaires to validly and reliably measure attitudes to oral health. Material and Methods: A bibliographic review was carried out using the following databases, Medline (PubMed), SCOPUS and Web of Science from the year 2016 to 2021, using the keywords: (questionnaire* OR survey*) AND (attitude* OR behav*) AND ("oral health" OR "dental care") AND (validity OR reliability). Results: A total of 234 original articles were found in the databases, only 22 met the selection criteria, of which 13 were aimed at patients and nine at health professionals. Evidence of validity and reliability was determined using "COnsensus-based Standards for the selection of health status Measurement INstruments" (COSMIN). Conclusions: Most of the articles partially meet the validity and reliability criteria. Key words:Questionnaire, attitude, behavior, oral health, validity and reliability.

Clinical Utility of HeartLogic, a Multiparametric Telemonitoring System, in Heart Failure.

Telemonitoring through multiple variables measured on cardiac devices has the potential to improve the follow-up of patients with heart failure. The HeartLogic algorithm (Boston Scientific), implemented in some implantable cardiac defibrillators and cardiac resynchronisation therapy, allows monitoring of the nocturnal heart rate, respiratory movements, thoracic impedance, physical activity and the intensity of heart tones, with the aim of predicting major clinical events. Although HeartLogic has demonstrated high sensitivity for the detection of heart failure decompensations, its effects on hospitalisation and mortality in randomised clinical trials has not yet been corroborated. This review details how the HeartLogic algorithm works, compiles available evidence from clinical studies, and discusses its application in daily clinical practice.

Remote heart failure management using the HeartLogic algorithm. RE-HEART registry.

INTRODUCTION AND OBJECTIVES: HeartLogic is a multiparametric algorithm incorporated into implantable cardioverter-defibrillators (ICD). The associated alerts predict impending heart failure (HF) decompensations. Our objective was to analyze the association between alerts and clinical events and to describe the implementation of a protocol for remote management in a multicenter registry. METHODS: We evaluated study phase 1 (the investigators were blinded to the alert state) and phases 2 and 3 (after HeartLogic activation, managed as per local practice and with a standardized protocol, respectively). RESULTS: We included 288 patients from 15 centers. In phase 1, the median observation period was 10 months and there were 73 alerts (0.72 alerts/patient-y), with 8 hospitalizations and 2 emergency room admissions for HF (0.10 events/patient-y). There were no HF hospitalizations outside the alert period. In the active phases, the median follow-up was 16 (95%CI, 15-22) months and there were 277 alerts (0.89 alerts/patient-y); 33 were associated with HF hospitalizations or HF death (n=6), 46 with minor decompensations, and 78 with other events. The unexplained alert rate was 0.39 alerts/patient-y. Outside the alert state, there was only 1 HF hospitalization and 1 minor HF decompensation. Most alerts (82% in phase 2 and 81% in phase 3; P=.861) were remotely managed. The median NT-proBNP value was higher within than outside the alert state (7378 vs 1210 pg/mL; P <.001). CONCLUSIONS: The HeartLogic index was frequently associated with HF-related events and other clinically relevant situations, with a low rate of unexplained events. A standardized protocol allowed alerts to be safely and remotely detected and appropriate action to be taken on them.

[Spanish Catheter Ablation Registry. 20th Official Report of the Heart Rhythm Association of the Spanish Society of Cardiology (2020)]. / Registro Español de Ablación con Catéter. XX Informe Oficial de la Asociación del Ritmo Cardiaco de la Sociedad Española de Cardiología (2020).

INTRODUCTION AND OBJECTIVES: This article reports the results of the 2020 Spanish Catheter Ablation Registry, a year marked by the SARS-CoV-2 pandemic. METHODS: Data were collected retrospectively through completion and return of a specific form by the participating centers. RESULTS: Data from 97 centers (67 public, 30 private) were analyzed. A total of 15 169 ablation procedures were reported with a mean of 155 ± 117 and a median [interquartile range] of 115 [62-227]. Because of the SARS-CoV-2 pandemic, both procedures and participating centers markedly decreased (-3380 procedures, -18%) and there were 5 centers less than in 2019. The most common procedure continued to be atrial fibrillation ablation (4513; 30%), well ahead of the remaining substrates, followed by ablation of the cavotricuspid isthmus (3188; 21%), and intranodal re-entry tachycardia (2808; 18%). Ablation of these 3 substrates continued to form the bulk of the procedures. The total success rate was slightly lower than in previous years (88%) with a similar complication rate (n = 309; 2%) and mortality (n = 7; 0.04%). A total of 243 procedures were performed in pediatric patients (1.6%). CONCLUSIONS: The Spanish Catheter Ablation Registry systematically and continuously reflects the national trajectory, which, in 2020, was markedly affected by the SARS-CoV-2 pandemic. Although slightly lower than in previous years, the success rate remained high, with a low complication rate.Full English text available from:www.revespcardiol.org/en.

Spanish Catheter Ablation Registry. 20th Official Report of the Heart Rhythm Association of the Spanish Society of Cardiology (2020).

INTRODUCTION AND OBJECTIVES: This article reports the results of the 2020 Spanish Catheter Ablation Registry, a year marked by the SARS-CoV-2 pandemic. METHODS: Data were collected retrospectively through completion and return of a specific form by the participating centers. RESULTS: Data from 97 centers (67 public, 30 private) were analyzed. A total of 15 169 ablation procedures were reported with a mean of 155±117 and a median [interquartile range] of 115 [62-227]. Because of the SARS-CoV-2 pandemic, both procedures and participating centers markedly decreased (-3380 procedures,-18%) and there were 5 centers less than in 2019. The most common procedure continued to be atrial fibrillation ablation (4513; 30%), well ahead of the remaining substrates, followed by ablation of the cavotricuspid isthmus (3188; 21%), and intranodal re-entry tachycardia (2808; 18%). Ablation of these 3 substrates continued to form the bulk of the procedures. The total success rate was slightly lower than in previous years (88%) with a similar complication rate (n=309; 2%) and mortality (n=7; 0.04%). A total of 243 procedures were performed in pediatric patients (1.6%). CONCLUSIONS: The Spanish Catheter Ablation Registry systematically and continuously reflects the national trajectory, which, in 2020, was markedly affected by the SARS-CoV-2 pandemic. Although slightly lower than in previous years, the success rate remained high, with a low complication rate.

[Severe infections in a cohort of patients with systemic lupus erythematosus]. / Infecciones graves en una cohorte de pacientes con lupus eritematoso sistémico.

BACKGROUND AND OBJECTIVE: To study severe infectious complications in a cohort of patients with systemic lupus erythematosus (SLE). PATIENTS AND METHOD: Retrospective study of 705 patients followed from January 1980 to January 2008. Data are expressed in percentages. RESULTS: The frequency of severe infectious was 38.6%. The etiology was bacterial 54.4%, viric 30.4% and opportunist in 15.2% patients. Involved organs were: Lung 38.2%, kidney 48.9%, central nervous system 43%. 43.75% patients received pulsed ciclofosfamide therapy and 88.6% received glucocorticoids (39.7% pulsed). The mortality was 27.7%. CONCLUSIONS: At present, infection is an important cause of mortality in patients with SLE. Early diagnosis of infectious complications is very important in SLE.

[Thyroid dysfunction in patients with pulmonary arterial hypertension. A cohort study of 58 patients]. / Disfunción tiroidea en pacientes con hipertensión arterial pulmonar. Estudio de una cohorte de 58 pacientes.

BACKGROUND AND OBJECTIVE: Thyroid disease (TD) is more prevalent in patients with pulmonary arterial hypertension (PAH) than in the general population. The frequency and the cause of this association are not well established. We aimed to quantify and analyze the incidence and characteristics of TD in a cohort of PAH patients (idiopathic or preferentially associated with systemic diseases) and review the literature. PATIENTS AND METHOD: Fifty eight PAH patients were prospectively studied, according to a previously established protocol (that included right heart catheterization); TSH, T(4), and antithyroglobulin and antiperoxidase antibodies were determined. TD was defined as an abnormal TSH level and/or elevated antithyroid antibodies (TAbs). Clinical, biological and hemodynamic variables were compared between patients with and without TD. RESULTS: TD was detected in 30 patients (51%): high TSH levels were observed in 21 (36,21%); hyperthyroidism in 2 (3,45%); and TAbs in 16 of 54 (27,59%), 7 of whom were euthyroid. In the TD group, PAH evolution time was longer (4,62 vs 2,61 years; P=.005, CI 95%, 0,63-3,38), more patients were in functional class IV (13;43,3% vs 5;15,8%, P=.046, CI 95% ,0,05-11,75), cardiac output was lower (P=.032, CI 95%, 3,16-4,89) and epoprostenol treatment was more frequently used (14;46,6% vs 4;14,3%, P=.008, CI 95%, 1,46-18,85; OR=5,25). CONCLUSIONS: The frequency of TD detected in this PAH cohort reaches 51% and it was associated with a longer evolution time of PAH and worse hemodynamic situation. Although epoprostenol was used more frequently in TD patients, a causal relationship with TD could not be established.

Specific genetic markers for detecting subtypes of dengue virus serotype-2 in isolates from the states of Oaxaca and Veracruz, Mexico.

BACKGROUND: Dengue (DEN) is an infectious disease caused by the DEN virus (DENV), which belongs to the Flavivirus genus in the family Flaviviridae. It has a (+) sense RNA genome and is mainly transmitted to humans by the vector mosquito Aedes aegypti. Dengue fever (DF) and dengue hemorrhagic fever (DHF) are caused by one of four closely related virus serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Epidemiological and evolutionary studies have indicated that host and viral factors are involved in determining disease outcome and have proved the importance of viral genotype in causing severe epidemics. Host immune status and mosquito vectorial capacity are also important influences on the severity of infection. Therefore, an understanding of the relationship between virus variants with altered amino acids and high pathogenicity will provide more information on the molecular epidemiology of DEN. Accordingly, knowledge of the DENV serotypes and genotypes circulating in the latest DEN outbreaks around the world, including Mexico, will contribute to understanding DEN infections. RESULTS: 1. We obtained 88 isolates of DENV, 27 from Oaxaca and 61 from Veracruz. 2. Of these 88 isolates, 16 were serotype 1; 62 serotype 2; 7 serotype 3; and 2 serotype 4. One isolate had 2 serotypes (DENV-2 and -1). 3. Partial nucleotide sequences of the genes encoding C- prM (14 sequences), the NS3 helicase domain (7 sequences), the NS5 S-adenosyl methionine transferase domain (7 sequences) and the RNA-dependent RNA polymerase (RdRp) domain (18 sequences) were obtained. Phylogenetic analysis showed that DENV-2 isolates belonged to the Asian/American genotype. In addition, the Asian/American genotype was divided into two clusters, one containing the isolates from 2001 and the other the isolates from 2005-2006 with high bootstrap support of 94%. CONCLUSION: DENV-2 was the predominant serotype in the DF and DHF outbreak from 2005 to 2006 in Oaxaca State as well as in the 2006 outbreak in Veracruz State, with the Asian/American genotype prevalent in both states. Interestingly, DENV-1 and DENV-2 were the only serotypes related to DHF cases. In contrast, DENV-3 and DENV-4 were poorly represented according to epidemiological data reported in Mexico. We found that isoleucine was replaced by valine at residue 106 of protein C in the isolates from these 2005-2006 outbreaks and in those from the 1997, 1998 and 2001 outbreaks in the Caribbean islands. We suggested that this amino acid change may be used as a signature for isolates arising in the Caribbean islands and pertaining to the Asian/American genotype. Other amino acid changes are specific for the Asian/American, Asian and American strains.

[Experience with imatinib to treat pulmonary arterial hypertension]. / Experiencia en el tratamiento de la hipertensión arterial pulmonar con imatinib.

Despite advances in the treatment of patients with pulmonary arterial hypertension (PAH), survival has not improved greatly (is still very affected). Imatinib, an antagonist of platelet-derived growth factor with antiproliferative activity, has been effective in experimental models and clinically in several published reports. We report the results of imatinib therapy in 4 patients with PAH (functional class IV) who were refractory to treatment with drug combinations for this condition. The final outcome was favorable in only 1 of the 4 cases. In this case, the patient was in functional class III and his hemodynamic parameters had improved significantly within 5 months after starting therapy. However, the patient died as a result of severe toxic hepatitis in which imatinib may have played a role. The present report adds to the few already in the literature (4 cases) and suggests that care should continue to be shown when using imatinib to treat PAH.