Mitral regurgitation carries greater prognostic significance than mitral stenosis in patients undergoing transcatheter aortic valve replacement.

AIMS: This study assessed the outcomes of concomitant mitral valve disease and severe aortic stenosis in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS: Echocardiographic data of 813 patients with severe aortic stenosis undergoing transfemoral TAVR were collected, and clinical outcomes were analyzed for individuals with mitral stenosis and mitral regurgitation. RESULTS: The final cohort includes 788 patients with severe calcific aortic stenosis. Among single parameters of mitral stenosis, a smaller baseline mitral valve area (MVA) by the continuity equation and higher postprocedural mean mitral gradients (MMG) were associated with an increased risk of death at 1 year (P-values 0.02 and <0.01, respectively), but no correlation with outcomes was demonstrated after multivariate adjustment for major prognosticators. Mitral stenosis (based on MVA + MMG) was not associated with complications or mortality. Mitral regurgitation was present in 94.6% of the population at baseline and regressed by at least one grade post-TAVR in 28% of the patients. The improvement in mitral regurgitation was associated with a greater prosthetic effective orifice area (P-value 0.03). Significant (at least moderate) residual mitral regurgitation was correlated with short-term complications and shown to be an independent predictor of 1-year mortality (P-value 0.02, odds ratio (OR) 5.37, confidence interval 1.34-21.5). CONCLUSION: Mitral regurgitation has a greater impact on TAVR patients than mitral stenosis as assessed by functional methods.

ADAM12 expression is upregulated in cancer cells upon radiation and constitutes a prognostic factor in rectal cancer patients following radiotherapy.

Radiotherapy is one of the most common cancer treatments, yet, some patients require high doses to respond. Therefore, the development of new strategies leans toward personalizing therapy to avoid unnecessary burden on cancer patients. This approach prevents the administration of ineffective treatments or uses combination strategies to increase the sensitivity of cancer cells. ADAM12 has been shown to be upregulated in many cancers and correlate with poor survival and chemoresistance, thus making it a potential candidate responsible for radioresistance. Here, we show that ADAM12 expression is upregulated in response to irradiation in both mouse and human cancer cells in vitro, as well as in tumor tissues from rectal cancer patients. Interestingly, the expression of ADAM12 following radiotherapy correlates with the initial disease stage and predicts the response of rectal cancer patients to the treatment. While we found no cell-autonomous effects of ADAM12 on the response of colon cancer cells to irradiation in vitro, depletion of ADAM12 expression markedly reduced the tumor growth of irradiated cancer cells when subcutaneously transplanted in syngeneic mice. Interestingly, loss of cancer cell-derived ADAM12 expression increased the number of CD31+FAP- cells in murine tumors. Moreover, conditioned medium from ADAM12-/- colon cancer cells led to increased tube formation when added to endothelial cell cultures. Thus, it is tempting to speculate that altered tumor vascularity may be implicated in the observed effect of ADAM12 on response to radiotherapy in rectal cancer. We conclude that ADAM12 represents a promising prognostic factor for stratification of rectal cancer patients receiving radiotherapy and suggest that targeting ADAM12 in combination with radiotherapy could potentially improve the treatment response.

A Mitosome With Distinct Metabolism in the Uncultured Protist Parasite Paramikrocytos canceri (Rhizaria, Ascetosporea).

Ascetosporea are endoparasites of marine invertebrates that include economically important pathogens of aquaculture species. Owing to their often-minuscule cell sizes, strict intracellular lifestyle, lack of cultured representatives and minimal availability of molecular data, these unicellular parasites remain poorly studied. Here, we sequenced and assembled the genome and transcriptome of Paramikrocytos canceri, an endoparasite isolated from the European edible crab Cancer pagurus. Using bioinformatic predictions, we show that P. canceri likely possesses a mitochondrion-related organelle (MRO) with highly reduced metabolism, resembling the mitosomes of other parasites but with key differences. Like other mitosomes, this MRO is predicted to have reduced metabolic capacity and lack an organellar genome and function in iron-sulfur cluster (ISC) pathway-mediated Fe-S cluster biosynthesis. However, the MRO in P. canceri is uniquely predicted to produce ATP via a partial glycolytic pathway and synthesize phospholipids de novo through the CDP-DAG pathway. Heterologous gene expression confirmed that proteins from the ISC and CDP-DAG pathways retain mitochondrial targeting sequences that are recognized by yeast mitochondria. This represents a unique combination of metabolic pathways in an MRO, including the first reported case of a mitosome-like organelle able to synthesize phospholipids de novo. Some of these phospholipids, such as phosphatidylserine, are vital in other protist endoparasites that invade their host through apoptotic mimicry.

Artificial Intelligence in Echocardiography.

Artificial intelligence in diagnostic cardiac-imaging platforms is advancing rapidly. In particular, artificial intelligence algorithms have increased the efficiency and accuracy of echocardiographic cardiovascular imaging, resulting in more complex echocardiographic imaging techniques and expanded use among noncardiologists. Here, we provide an overview of real-world applications of artificial intelligence in echocardiography including automatic high-quality computer-optimized image acquisition sequences, automated measurements, and algorithms for the rapid and accurate interpretation of cardiac physiology. These advances will not replace physicians but will improve their productivity, workflow, and diagnostic performance.

Suppressive treatment with monepantel and the fast selection for phenotypically resistant trichostrongylids of sheep.

Gastrointestinal parasite control has been a major challenge to livestock due to the failure of anthelmintic treatments. Monepantel (MNT) was introduced in 2009 as an alternative treatment option showing a new mechanism of action against nematode parasites. To study the response of MNT in a suppressive regime, 45-Suffolk and White Dorper naturally infected sheep were divided into one of three groups, G1: control ­ with no treatment, G2: MNT at 2.5 mg kg−1 live weight (LW) PO every 30 days, and G3: MNT at 4.0 mg kgLW−1 PO every 30 days for 6 months. Every 15 days, the animals were individually weighed (body weight, BW) and checked for Famacha (FMC) and body condition score (BCS). The efficacy of MNT was evaluated weekly by fecal egg count (FEC) every month. FEC showed >97% efficacy at the start of the experiment, revealing a significant reduction for G2 (28%) and G3 (39%) in the following months. There was no treatment, BW or BCS effect between treatments; however, there was a period (P < 0.0001) and a treatment vs period interaction (P < 0.0001) for BW. The data revealed that MNT at a therapeutic and suppressive dose had a non-linear polynomial efficacy regression (R2) of 0.988 and 0.992, respectively. This original experiment demonstrates how short-interval and suppressive MNT treatments would rapidly select Haemonchus contortus, showing a fast susceptible-resistance phenotypic population replacement. Therefore, it is suggested that MNT might be carefully used in parasite control programmes alongside other management strategies (i.e. FMC, BCS) to reduce treatment frequency and the selection process for resistance.

Hydrogen metabolism: A eukaryote taps into the electron sink.

The ability to harvest reducing power from molecular hydrogen was once considered a prokaryotic trait. New research challenges this notion by finding the first eukaryotic organism capable of oxidizing hydrogen.

PharmVar GeneFocus: CYP2C9.

The Pharmacogene Variation Consortium (PharmVar) catalogues star (*) allele nomenclature for the polymorphic human CYP2C9 gene. Genetic variation within the CYP2C9 gene locus impacts the metabolism or bioactivation of many clinically important drugs, including nonsteroidal anti-inflammatory drugs, phenytoin, antidiabetic agents, and angiotensin receptor blockers. Variable CYP2C9 activity is of particular importance regarding efficacy and safety of warfarin and siponimod as indicated in their package inserts. This GeneFocus provides a comprehensive overview and summary of CYP2C9 and describes how haplotype information catalogued by PharmVar is utilized by the Pharmacogenomics Knowledgebase and the Clinical Pharmacogenetics Implementation Consortium.

Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome?

BACKGROUND: Persistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation. OBJECTIVE: The goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT. METHODS: We analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta-analyses, incorporating data from previously published literature. RESULTS: Rates of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta-analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First-degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates. CONCLUSIONS: Our findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Acceptability, Feasibility, and Utility of Integrating Pharmacogenetic Testing into a Child Psychiatry Clinic.

Pharmacogenetic (PGx) testing is a tool to identify patients at a higher risk of adverse events or treatment failure. The concern for unwanted side effects can limit medication adherence, particularly in children and adolescents. We conducted a pragmatic study to evaluate the acceptability and feasibility and gather pilot data on the utility of PGx testing in a child and adolescent psychiatry clinic. Both physicians and families participated in the study and answered pre-survey and post-survey questionnaires to examine their attitudes toward PGx testing. Patients were randomized into implementation (N = 25) and control groups (N = 24) and underwent PGx testing at the beginning or end of the study, respectively. Clinical consult notes with genotype-guided recommendations were provided to physicians for their consideration in clinical decisions. Patient-reported symptom severity and antidepressant-related side effects were assessed at baseline and for 12 weeks. Both participating physicians and families agreed that PGx testing is a useful tool to improve medication selection. The time from sample collection to having PGx test results was ~ 10 days and 15 days to having consult notes available, which may have impaired test utility in clinical decision making. There were no differences in any clinical end point between the implementation and control arms; however, there were higher antidepressant side effect scores for CYP2D6 poor and intermediate metabolizers after the eighth week of treatment. Our findings revealed benefits and pitfalls with the use of PGx testing in the real-world clinical setting, which may inform the methodology of a larger trial focused on outcomes.

PharmVar GeneFocus: CYP2C19.

The Pharmacogene Variation Consortium (PharmVar) catalogues star (*) allele nomenclature for the polymorphic human CYP2C19 gene. CYP2C19 genetic variation impacts the metabolism of many drugs and has been associated with both efficacy and safety issues for several commonly prescribed medications. This GeneFocus provides a comprehensive overview and summary of CYP2C19 and describes how haplotype information catalogued by PharmVar is utilized by the Pharmacogenomics Knowledgebase and the Clinical Pharmacogenetics Implementation Consortium (CPIC).

Low-frequency variants at the CYP2C9 locus among Puerto Rican patients on warfarin: in silico predictions of functionality and conservation.

Aim: Perform in silico predictions of functional consequences of CYP2C9 variants identified by next-generation sequencing in Puerto Ricans. Methods: Identified low-frequency CYP2C9 variants (minor allele frequencies <2%) were evaluated using the Combined Annotation-Dependent Depletion (CADD v1.3) tools and molecular modeling/docking analysis to predict impact on CYP2C9 activity. Results:CYP2C9*5,*8,*9,*11,*12,*21 and a novel *61 induce conformational changes that affect the binding site of S-warfarin. Most of these deleterious variants occur at higher frequency among individuals with large African ancestry. Conclusion: The unfavorable distance of S-warfarin from heme group, and low-binding interactions due to these CYP2C9 variants, suggest major complications during warfarin therapy. This study contributes to the field by predicting functional alterations of rare CYP2C9 variants for the first time in Hispanics.

Comorbilidades neurológicas y su relación con la velocidad de la marcha en adultos mayores del Centro Médico Naval Cirujano Mayor Santiago Távara 2010-2015 / Neurological comorbidities and its association with gait speed in older adults of the Naval Medical Center Cirujano Mayor Santiago Távara 2010-2015

Objetivo: Determinar la relación entre presencia de comorbilidades neurológicas y velocidad de la marcha en adultos mayores del Centro Médico Naval “Cirujano Mayor Santiago Távara” 2010-2015. Material y Métodos: Estudio observacional retrospectivo mediante análisis secundario de base de datos. La muestra fue conformada por 1785 adultos mayores. Para determinar la relación entre variables se utilizó Chi-cuadrado con un nivel de significación del 5% y el programa STATA v.14. Resultados: El 18,7% de los probandos presentaron enfermedad de Parkinson, 44,9% presentaron deterioro cognitivo leve y sólo el 3,1% presentó evidencia de enfermedad cerebrovascular. Existieron diferencias significativas respecto a la edad (p<0,001) y sexo (p=0,043) según la velocidad de marcha (mayor en mujeres de 80 años o más). Hubo relación significativa entre el deterioro cognitivo leve (p<0,001) y la enfermedad cerebro- vascular (p=0,002) con la velocidad de marcha. La probabilidad de una velocidad de marcha lenta ajustada por antecedente de enfermedad de Parkinson, edad y sexo para aquellos con deterioro cognitivo leve fue de 2,13 (IC95% 1,72-2,63) y para aquellos con enfermedad cerebrovascular fue de 1,79 (IC95% 1,01-3,20). Conclusiones: La lentitud de marcha se presentó mayormente en mujeres de 80 o más años de edad y se relacionó significativamente con el deterioro cognitivo leve y enfermedad cerebrovascular, pero no con la enfermedad de Parkinson.

Objective: To determine the association between presence of neurological comorbidities and walking speed in older adults attended at the Naval Medical Center “Cirujano Mayor Santiago Távara” 2010-2015. Methods: Observational retrospective study through secondary analysis of a database of 1785 older adults. To determine the relationship between variables, the Chi-square test with a level of significance of 5%, and the STATA v.14 program were used. Results: 18.7% of the probands had Parkinson’s disease, 44.9% had mild cognitive impairment, and only 3.1% had cerebrovascular disorder. There were significant differences in walking speed with respect to advanced age and female sex (greater in 80 y.o. or older females). There was a significant relationship between mild cognitive impairment and cerebrovascular disorder with walking speed. The probability of a slow walking speed adjusted for Parkinson’s disease diagnosis, age and sex for those with mild cognitive impairment was 2.13 (IC95% 1.72-2.63), and for those with cerebrovascular disease, 1.79 (IC95% 1.01-3.20). Conclusions: Slow walking was presented mainly in women over 80 years of age, and was significantly related to mild cognitive impairment and cerebrovascular disorder, but not to Parkinson’s disease

CYP2C9*61, a rare missense variant identified in a Puerto Rican patient with low warfarin dose requirements.

Warfarin continues to be the mainstay therapy for preventing thrombus formation. Although pharmacogenetic algorithms have shown higher predictability of the optimal warfarin dose and lower occurrence of bleeding episodes, they often do not include ethno-specific genetic variants relevant to non-Europeans. This case report describes a rare missense variant at exon 9 of CYP2C9 (rs202201137; c.1370A>G transition; p.Asn457Ser) found in a Puerto Rican patient with low warfarin dose requirements (3 mg/day). The haplotype characterized by two amino acid changes, Asn457Ser and Arg144Cys (rs1799853; c.430C>T), has been designated CYP2C9*61 by the Pharmacogene Variation Consortium. According to prediction scores assessed with the Combined Annotation Dependent Depletion tool, CYP2C9*61 (p.Asn457Ser) was classified as nondeleterious, therefore its impact on CYP2C9 enzymatic activity cannot be postulated.

Ethnic group inequalities in coverage with reproductive, maternal and child health interventions: cross-sectional analyses of national surveys in 16 Latin American and Caribbean countries.

BACKGROUND: Latin American and Caribbean populations include three main ethnic groups: indigenous people, people of African descent, and people of European descent. We investigated ethnic inequalities among these groups in population coverage with reproductive, maternal, newborn, and child health interventions. METHODS: We analysed 16 standardised, nationally representative surveys carried out from 2004 to 2015 in Latin America and the Caribbean that provided information on ethnicity or a proxy indicator (household language or skin colour) and on coverage of reproductive, maternal, newborn, and child health interventions. We selected four outcomes: coverage with modern contraception, antenatal care coverage (defined as four or more antenatal visits), and skilled attendants at birth for women aged 15-49 years; and coverage with three doses of diphtheria-pertussis-tetanus (DPT3) vaccine among children aged 12-23 months. We classified women and children as indigenous, of African descent, or other ancestry (reference group) on the basis of their self-reported ethnicity or language. Mediating variables included wealth quintiles (based on household asset indices), woman's education, and urban-rural residence. We calculated crude and adjusted coverage ratios using Poisson regression. FINDINGS: Ethnic gaps in coverage varied substantially from country to country. In most countries, coverage with modern contraception (median coverage ratio 0·82, IQR 0·66-0·92), antenatal care (0·86, 0·75-0·94), and skilled birth attendants (0·75, 0·68-0·92) was lower among indigenous women than in the reference group. Only three countries (Nicaragua, Panama, and Paraguay) showed significant gaps in DPT3 coverage between the indigenous and the reference groups. The differences were attenuated but persisted after adjustment for wealth, education, and residence. Women and children of African descent showed similar coverage to the reference group in most countries. INTERPRETATION: The lower coverage levels for indigenous women are pervasive, and cannot be explained solely by differences in wealth, education, or residence. Interventions delivered at community level-such as vaccines-show less inequality than those requiring access to services, such as birth attendance. Regular monitoring of ethnic inequalities is essential to evaluate existing initiatives aimed at the inclusion of minorities and to plan effective multisectoral policies and programmes. FUNDING: The Bill & Melinda Gates Foundation (through the Countdown to 2030 initiative) and the Wellcome Trust.

Warfarin Anticoagulation Therapy in Caribbean Hispanics of Puerto Rico: A Candidate Gene Association Study.

Existing algorithms account for ~50% of observed variance in warfarin dose requirements after including common polymorphisms. However, they do not perform as well in populations other than Caucasians, in part because some ethno-specific genetic variants are overlooked. The objective of the present study was to identify genetic polymorphisms that can explain variability in warfarin dose requirements among Caribbean Hispanics of Puerto Rico. Next-Generation Sequencing of candidate genes CYP2C9 and VKORC1 and genotyping by DMET® Plus Assay of cardiovascular patients were performed. We also aimed at characterizing the genomic structure and admixture pattern of this study cohort. Our study used the Extreme Discordant Phenotype approach to perform a case-control association analysis. The CYP2C9 variant rs2860905, which was found in all the major haplotypes occurring in the Puerto Rican population, showed stronger association with warfarin sensitivity (<4 mg/day) than common variants CYP2C9*2 and CYP2C9*3. Although, CYP2C9*2 and CYP2C9*3 are separately contained within two of the haplotypes, 10 subjects with the sensitive phenotype were carriers of only the CYP2C9 rs2860905 variant. Other polymorphisms in CES2 and ABCB1 were found to be associated with warfarin resistance. Incorporation of rs2860905 in a regression model (R2 = 0.63, MSE = 0.37) that also includes additional genetics (i.e., VKORC1-1639 G>A; CYP2C9 rs1856908; ABCB1 c.IVS9-44A>G/ rs10276036; CES2 c.269-965A>G/ rs4783745) and non-genetic factors (i.e., hypertension, diabetes and age) showed better prediction of warfarin dose requirements than CYP2C9*2 and CYP2C9*3 combined (partial R2 = 0.132 vs. 0.023 and 0.007, respectively, p < 0.001). The genetic background of Puerto Ricans in the study cohort showed a tri-hybrid admixture pattern, with a slightly higher than expected contribution of Native American ancestry (25%). The genomic diversity of Puerto Ricans is highlighted by the presence of four different major haplotype blocks in the CYP2C9 locus. Although, our findings need further replication, this study contributes to the field by identifying novel genetic variants that increase predictability of stable warfarin dosing among Caribbean Hispanics.

A Novel Admixture-Based Pharmacogenetic Approach to Refine Warfarin Dosing in Caribbean Hispanics.

AIM: This study is aimed at developing a novel admixture-adjusted pharmacogenomic approach to individually refine warfarin dosing in Caribbean Hispanic patients. PATIENTS & METHODS: A multiple linear regression analysis of effective warfarin doses versus relevant genotypes, admixture, clinical and demographic factors was performed in 255 patients and further validated externally in another cohort of 55 individuals. RESULTS: The admixture-adjusted, genotype-guided warfarin dosing refinement algorithm developed in Caribbean Hispanics showed better predictability (R2 = 0.70, MAE = 0.72mg/day) than a clinical algorithm that excluded genotypes and admixture (R2 = 0.60, MAE = 0.99mg/day), and outperformed two prior pharmacogenetic algorithms in predicting effective dose in this population. For patients at the highest risk of adverse events, 45.5% of the dose predictions using the developed pharmacogenetic model resulted in ideal dose as compared with only 29% when using the clinical non-genetic algorithm (p<0.001). The admixture-driven pharmacogenetic algorithm predicted 58% of warfarin dose variance when externally validated in 55 individuals from an independent validation cohort (MAE = 0.89 mg/day, 24% mean bias). CONCLUSIONS: Results supported our rationale to incorporate individual's genotypes and unique admixture metrics into pharmacogenetic refinement models in order to increase predictability when expanding them to admixed populations like Caribbean Hispanics. TRIAL REGISTRATION: ClinicalTrials.gov NCT01318057.

Potential of a Pharmacogenetic-Guided Algorithm to Predict Optimal Warfarin Dosing in a High-Risk Hispanic Patient: Role of a Novel NQO1*2 Polymorphism.

Deep abdominal vein thrombosis is extremely rare among thrombotic events secondary to the use of contraceptives. A case to illustrate the clinical utility of ethno-specific pharmacogenetic testing in warfarin management of a Hispanic patient is reported. A 37-year-old Hispanic Puerto Rican, non-gravid female with past medical history of abnormal uterine bleeding on hormonal contraceptive therapy was evaluated for abdominal pain. Physical exam was remarkable for unspecific diffuse abdominal tenderness, and general initial laboratory results-including coagulation parameters-were unremarkable. A contrast-enhanced computed tomography showed a massive thrombosis of the main portal, splenic, and superior mesenteric veins. On admission the patient was started on oral anticoagulation therapy with warfarin at 5 mg/day and low-molecular-weight heparin. The prediction of an effective warfarin dose of 7.5 mg/day, estimated by using a recently developed pharmacogenetic-guided algorithm for Caribbean Hispanics, coincided with the actual patient's warfarin dose to reach the international normalized ratio target. We speculate that the slow rise in patient's international normalized ratio observed on the initiation of warfarin therapy, the resulting high risk for thromboembolic events, and the required warfarin dose of 7.5 mg/day are attributable in some part to the presence of the NQO1*2 (g.559C>T, p.P187S) polymorphism, which seems to be significantly associated with resistance to warfarin in Hispanics. By adding genotyping results of this novel variant, the predictive model can inform clinicians better about the optimal warfarin dose in Caribbean Hispanics. The results highlight the potential for pharmacogenetic testing of warfarin to improve patient care.

O rituximabe como uma opção para pacientes com vasculite sistêmica grave refratária à terapia convencional: relato de sete casos e revisão de literatura / Rituximab as an alternative for patients with severe systemic vasculitis refractory to conventional therapy: report of seven cases and literature review

Resumo O maior entendimento das bases fisiopatológicas e do comportamento das vasculites sistêmicas, aliado ao desenvolvimento de regimes terapêuticos com perfil de segurança e eficácia cada vezes melhores, modificou drasticamente o prognóstico dos pacientes diagnosticados com essas entidades clínicas. Recentemente, o emprego do rituximabe no tratamento de pacientes com vasculites ANCA associadas em ensaios clínicos randomizados se mostrou uma opção importante em casos selecionados, especialmente pacientes refratários ou intolerantes à terapia-padrão com ciclofosfamida e corticosteroides. O presente artigo traz o relato de sete casos de vasculites sistêmicas com tratamento bem-sucedido com rituximabe.

Abstract The greater understanding of pathophysiology and behavior of systemic vasculitis, together with the development of therapeutic regimens with increasingly better safety and efficacy profiles, dramatically changed the prognosis of patients diagnosed with these clinical entities. Recently, the use of rituximab in the treatment of patients with ANCA-associated vasculitis in randomized clinical trials showed an important alternative in selected cases, especially patients refractory or intolerant to standard therapy with cyclophosphamide and corticosteroids. This article presents the report of seven cases of systemic vasculitis successfully treated with rituximab.

Pharmacogenetics of healthy volunteers in Puerto Rico.

Puerto Ricans are a unique Hispanic population with European, Native American (Taino), and higher West African ancestral contributions than other non-Caribbean Hispanics. In admixed populations, such as Puerto Ricans, genetic variants can be found at different frequencies when compared to parental populations and uniquely combined and distributed. Therefore, in this review, we aimed to collect data from studies conducted in healthy Puerto Ricans and to report the frequencies of genetic polymorphisms with major relevance in drug response. Filtering for healthy volunteers or individuals, we performed a search of pharmacogenetic studies in academic literature databases without limiting the period of the results. The search was limited to Puerto Ricans living in the island, excluding those studies performed in mainland (United States). We found that the genetic markers impacting pharmacological therapy in the areas of cardiovascular, oncology, and neurology are the most frequently investigated. Coincidently, the top causes of mortality in the island are cardiovascular diseases, cancer, diabetes, Alzheimer's disease, and stroke. In addition, polymorphisms in genes that encode for members of the CYP450 family (CYP2C9, CYP2C19, and CYP2D6) are also available due to their relevance in the metabolism of drugs. The complex genetic background of Puerto Ricans is responsible for the divergence in the reported allele frequencies when compared to parental populations (Africans, East Asians, and Europeans). The importance of reporting the findings of pharmacogenetic studies conducted in Puerto Ricans is to identify genetic variants with potential utility among this genetically complex population and eventually move forward the adoption of personalized medicine in the island.