A narrative review of the comparative safety of disease-modifying anti-rheumatic drugs used for the treatment of rheumatoid arthritis.

INTRODUCTION: Disease-modifying anti-rheumatic drugs (DMARDs) have improved the outcomes of patients with rheumatoid arthritis (RA). DMARDs are classified into three categories: conventional synthetic DMARDs, biological DMARDs (including biosimilars), and targeted synthetic DMARDs. DMARDs, by way of their effect on the immune system, are associated with increased risk of adverse events, including infections, malignancies, cardiovascular disease, gastrointestinal perforations, and other less common events. AREAS COVERED: In this narrative literature review performed with searches of the PubMed database from 1 January 2010 through 1 January 2023, we compare the risk of safety events between DMARDs using data from both randomized clinical trials and observational studies. EXPERT OPINION: DMARD use in RA is associated with higher rates of serious infections, tuberculosis reactivation, opportunistic infections, and possibly malignancies. Specific biologic DMARDs and higher doses are associated with elevated risks of various adverse events (gastrointestinal perforations, thromboembolism, serious infection). Shared decision-making is paramount when choosing a treatment regimen for patients based on their own comorbidities. JAKi are the newest class of medications used for RA with robust safety data provided in clinical trials. However, more real-world evidence and phase-IV pharmacovigilance data are needed to better understand comparative safety profile of DMARDs in RA.

Genetic diversity and structure in two epiphytic orchids from the montane forests of southern Ecuador: The role of overcollection on Masdevallia rosea in comparison with the widespread Pleurothallis lilijae.

Ecuador has a high diversity of orchids, but little is known about levels of genetic diversity for the great majority of species. Understanding how orchids might adapt to changes is crucial as deforestation and fragmentation of forest ecosystems threaten the survival of many epiphytic orchids that depend on other species, such as fungi and their host trees, for germination, growth, and establishment. Overcollection and the illegal trade are also major concerns for the survival of wild populations of orchids. Despite increasing awareness, effective interventions are often limited by a lack of data concerning the impacts that overexploitation might have. To fill this gap, we tested the effects of overcollection in the genetic diversity and structure of Masdevallia rosea, a narrow distributed epiphytic orchid historically collected in Ecuador, in comparison with the widely distributed Pleurothallis lilijae. Genotyping based on AFLPs showed reduced levels of diversity in wild populations but most especially in the overcollected, M. rosea. Overall, genetic admixture was high in P. lilijae segregating populations by altitude levels while fewer genetic groups were found in M. rosea. Genetic differentiation was low in both species. A spatial genetic structure was found in P. lilijae depending on altitude levels, while no spatial genetic structure was found in M. rosea. These results suggest different scenarios for the two species: while gene flow over long distance is possible in P. lilijae, the same seems to be unlikely in M. rosea possibly due to the low levels of individuals in the known populations. In situ and ex situ conservation strategies should be applied to protect the genetic pool in these epiphytic orchid species, and to promote the connectivity between wild populations. Adopting measures to reduce overexploitation and to understand the impacts of harvesting in wild populations are necessary to strengthen the legal trade of orchids.

An Unusual Presentation of Thyrotoxicosis: Leg Weakness and Hypokalemia in a 21-Year-Old Male.

Patients with hyperthyroidism or thyrotoxicosis present with an unspecific constellation of signs or symptoms such as palpitations, tremors, weight loss, or diarrhea. In some severe cases, hyperthyroidism can predispose patients to metabolic abnormalities and arrhythmias. Thyrotoxic periodic paralysis (TTP) is a rare, life-threatening complication or variant of hyperthyroidism associated with hypokalemia and muscle weakness that affects young Asian or Hispanic males between 20-40 years. TTP is reversible, and the management consists of beta-blockers, antithyroid therapy, and conservative potassium correction to prevent severe cardiovascular events such as ventricular arrhythmias with the improvement of transient muscle paralysis. We present a case of a 21-year-old Hispanic male complaining with symptoms of thyrotoxicosis, marked hypokalemia, and severe generalized muscle weakness. Physicians must be aware of this uncommon complication of thyrotoxicosis called thyrotoxic periodic paralysis (TTP) to avoid potassium overcorrection and all the endocrine associations with this pathology.

Evaluating the structure of commensalistic epiphyte-phorophyte networks: a comparative perspective of biotic interactions.

Epiphytic vascular plants comprise an essential part of the tropical flora and are a key component for ecosystem functioning. Some recent studies have used a network approach to investigate the interaction of epiphytes with host phorophytes at the community level. However, knowledge on commensalistic epiphyte-phorophyte network structure still lags behind with regard to other biotic interaction networks. Our goal was to provide a more complete overall perspective on commensalistic epiphyte-phorophyte interaction and its placement with respect to other better studied mutualistic interactions. We hypothesized that the intensity of the fitness effect of the different types of biotic interactions would determine the degree of specialization of the interacting organisms. Thus, commensalistic epiphyte-phorophyte interactions would have lower specialization than mutualistic interactions. We compiled and analysed the structural properties (nestedness, network specialization and modularity) of 12 commensalistic epiphyte-phorophyte networks and compared them with the same metrics to 11 ant-myrmecophyte, 86 pollination and 13 seed dispersal mutualistic networks. Epiphyte-phorophyte networks were nested and modular with regard to the corresponding null models and had greater nestedness than mutualistic networks, whereas specialization and modularity were significantly lower. Commensalistic epiphyte-phorophyte networks of interactions are both nested and modular, and hence, are structured in a similar way to most other types of networks that involve co-evolutionary interactions. Nevertheless, the nature and intensity of the ecological processes involved in the generation of these patterns is likely to differ. The lower values of modularity in commensalistic epiphyte-phorophyte networks are probably due to the low levels of specialization and the lack of co-evolutionary processes between the interacting partners.

Complex fine-scale spatial genetic structure in Epidendrum rhopalostele: an epiphytic orchid.

Orchid seeds are presumably dispersed by wind due to their very small size and thus can potentially travel long distances. However, the few related studies indicate that seeds fall close to their mother plants. Because seed dispersal and colonization patterns can have relevant consequences for long-term species persistence, we assessed the fine-scale genetic structure of the epiphytic orchid Epidendrum rhopalostele to provide insight into these patterns. All individuals in the studied population were georeferenced and genotyped with AFLP-markers. Genetic structure was evaluated at two levels (forest and tree) using three approaches: principal coordinates analysis, model-based clustering, and spatial autocorrelation analysis. Results showed two genetic groups, composed of individuals from almost every tree with orchids. Spatial autocorrelation analysis at the forest level found no significant genetic structure when all individuals were considered, but a pattern of genetic patches was revealed when the analysis was performed separately for each group. Genetic patches had an estimated diameter of 4 m and were composed of individuals from more than one tree. A weak genetic structure was detected at the tree level at distances less than 1.5 m. These results suggest that many seeds fall close to the mother plant and become established in the same host tree. Additionally, a sequential colonization process seems to be the predominant mode of expansion, whereby progeny from orchids in one tree colonize neighboring trees. Thus, the existence of two distinct genetic groups and the presence of genetic patches should be considered when seed sampling for ex situ conservation.

Estudio Transversal: Perfil Epidemiológico de Sífilis Notificada en el Instituto Nacional de Investigación en Salud Pública. Zonas 6 y 7 Ecuador / Cross-sectional Research: Epidemiological Profile of Syphilis Notified in the National Institute of Public Health Research. Zones 6 and 7 Ecuador

INTRODUCCIÓN: La sífilis constituye un desafío para la salud pública nacional y global por las repercusiones en la vida humana. El objetivo del estudio fue caracterizar el perfil epidemiológico de los casos de sífilis atendidos en el sistema de salud de las zonas 6 y 7. MÉTODOS: Estudio de corte transversal, de datos recogidos en los formularios de investigación/notificación de sífilis de todas las personas atendidas y diagnosticadas mediante pruebas de absorción de anticuerpos treponémicos fluorescentes. Los criterios de inclusión fueron los datos clínicos y epidemiológicos de sospecha para sífilis. Las variables analizadas fueron edad, sexo, procedencia, residencia y pruebas diagnósticas. Para el análisis de inferencia estadística se utilizó Odds Ratio y Chi2 mediante el programa Epi info 7.2 RESULTADOS: El 72 % de las personas diagnosticadas de sífilis tienen entre 20 a 49 años, 53 % del sexo femenino. Las pruebas confirmatorias resultaron reactivas en el 75 % de los casos, de los cuales el 27 % presentaron pruebas serológicas no reactivas y 77 % sin pruebas previas. Las provincias con mayor incidencia de casos fueron Cañar (93 %) y Morona Santiago (87 %) . Se detectaron como factores protectores el sexo femenino (OR 0.41; IC95 % 0.25 ­ 0.68) y la residencia en la provincia de Loja (OR 0.21; IC 95 % 0.10 ­ 0.46). CONCLUSIONES: La prevalencia de casos de sífilis se encuentra en el grupo etario de 20 a 49 años y de sexo masculino. Los factores protectores identificados de manera estadísticamente significativos fueron el sexo femenino y la residencia en la provincia de Loja. Se sugieren desarrollar estrategias para ampliar la cobertura en las personas con sospecha de sífilis, para emprender programas prevención y promoción de la salud.

BACKGROUND: Syphilis constitutes a challenge for national and global public health due to the repercussions on human life. The objective of the study was to characterize the epidemiological profile of the cases of syphilis treated in the health system of zones 6 and 7. METHODS: Cross-sectional study of secondary data collected in the form of investigation / notification of syphilis of all people attended and diagnosed by fluorescent treponemal antibody absorption tests. The inclusion criteria were the clinical and epidemiological data of suspicion for syphilis. The variables analyzed were age, sex, origin, residence and diagnostic tests. Odds Ratio and Chi2 were used for the statistical inference analysis using the Epi info 7.2 programs RESULTS: 72 % of people diagnosed with syphilis are between 20 and 49 years old, 53 % of women. The confirmatory tests were reactive in 75 % of the cases, of which 27 % presented non-reactive serological tests and 77 % without previous tests. The provinces with the highest incidence of cases were Cañar (93 %) and Morona Santiago (87 %). Protective factors were female sex (OR 0.41, 95 % CI 0.25 - 0.68) and residence in the province of Loja (OR 0.21, 95 % CI 0.10 - 0.46) CONCLUSIONS: The prevalence of cases of syphilis is found in the age group of 20 to 49 years andmale. The protective factors identified in a statistically significant manner were female sex and residence in the province of Loja. It is suggested to develop strategies to expand coverage in people with suspected syphilis, to undertake prevention and health promotion programs.

Tratamiento percutáneo de secuestro pulmonar gigante / Percutaneous treatment of giant pulmonary sequestration

El tratamiento clásico del secuestro pulmonar ha sido mediante cirugía con lobectomía o neumonectomía, actualmente hay alternativas de tratamiento menos invasivas tales como el cateterismo. Objetivo: Comunicar el tratamiento percutáneo de un secuestro pulmonar gigante en un lactante. Método: Estudio descriptivo. Historia clínica y base de datos del laboratorio de cateterismo. Resultados: lactante de 1,5 meses de edad en quien se realizó tratamiento por cateterismo de un gran secuestro pulmonar extralobar sintomático con un dispositivo tipo tapón desde la arteria femoral. Como complicaciones presentó síndrome de respuesta inflamatoria sistémica que requirió cuidados intensivos y disminución del pulso femoral que se trató con enoxaparina. Tiempo de internación: 10 días. Seguimiento: 2 años, pulsos femorales simétricos, gammagrafía pulmonar normal, tomografía informó regresión total del secuestro pulmonar. Conclusión: El tratamiento del secuestro pulmonar por cateterismo con los nuevos dispositivos es factible, efectivo y seguro aún en lactantes.

Classic treatment of pulmonary sequestration is by open thoracic surgery, currently there are alternatives treatment such as embolization. Objective: report the percutaneous treatment of pulmonary sequestration in a child. Method: descriptive study. Medical records and catheterization laboratory database. Results: an infant of 1.5 months in whom was performed treatment of symptomatic extralobar giant pulmonary sequestration by catetherization through implant a vascular plug device from femoral artery. As complications, there was a decrease in the femoral pulse that was treated with enoxaparin and also a systemic inflammatory response syndrome that required intensive care. Time of stay: 10 days. Follow-up: 2 years, symmetrical femoral pulses, normal lung scan, CT scan reported total regression of pulmonary sequestration. Conclusion: The treatmentt of pulmonary sequestration by catheterization with the new devices is feasible, effective and safe even in infants.

Cateterismo en hospital público ubicado en altas alturas: experiencia inicial de un centro / Catheterization in public hospital located at high altitudes: initial experience of a center

Los laboratorios de cateterismo o salas de hemodinamia localizados en países sudamericanos son escasos y más aún en ciudades en altas alturas. OBJETIVO: comunicar los resultados de un laboratorio de cateterismo de un hospital pediátrico público de tercer nivel andino localizado a 2860 metros sobre el nivel del mar. MÉTODO: estudio retrospectivo, descriptivo y corte transversal. Periodo: 2012 ­ 2016. Base de datos del laboratorio de cateterismo. RESULTADOS: se realizaron 711 procedimientos en 632 pacientes. Edad: mediana 4 años (rango: 0,002-17,8). Peso: mediana 13,7 kg (rango: 1,3-63,6). Género: femenino 57,9%, masculino 42,1%. Tipos de cateterismos: diagnósticos 63,3%, intervencionistas 38,2%. Complicaciones mayores y menores: 2,9 y 3.0% respectivamente, procedimientos sin complicaciones 94,1%. CONCLUSIONES: en este joven laboratorio de cateterismo pediátrico andino la mayoría de procedimientos fueron diagnósticos. El cierre del conducto arterioso persistente fue la intervención más frecuente. La tasa de complicaciones fue baja, comparable a la comunicada por otros grupos.

Pediatric catheterization laboratories in South American countries are scarce and these are located at high altitude even less OBJECTIVE: Report the results of pathologies treated in a catheterization laboratory of an andean public tertiary pediatric hospital which is located 2860 meters above sea level. METHOD: retrospective, descriptive and cross-sectional study. Period: 2012-2016. Data base of catheterization laboratory. RESULTS: 711 procedures in 632 patients were performed. Age: median 4 years (range: 0.002-17.8). Weight: median 13.7 kg (range: 1.3-63.6). Gender: female 57.9%, male 42.1%. Types of catheterizations: diagnostics 63.3%, interventional 38.2%. Major and minor complications: 2.9 and 3.0% respectively, procedures without complications: 94.1%. CONCLUSIONS: The majority of procedures were diagnostic type in this young Andean pediatric catheterization laboratory. The closure of patent ductus arteriosus was the most frequent intervention. The rate of complications was low, similar to those reported by other centers.

Mycorrhizal preferences and fine spatial structure of the epiphytic orchid Epidendrum rhopalostele.

PREMISE OF THE STUDY: The presence of compatible fungi is necessary for epiphytic orchid recruitment. Thus, identifying associated mycorrhizal fungi at the population level is essential for orchid conservation. Recruitment patterns may also be conditioned by factors such as seed dispersal range and specific environmental characteristics. METHODS: In a forest plot, all trees with a diameter at breast height >1 cm and all individuals of the epiphytic orchid Epidendrum rhopalostele were identified and mapped. Additionally, one flowering individual of E. rhopalostele per each host tree was randomly selected for root sampling and DNA extraction. KEY RESULTS: A total of 239 E. rhopalostele individuals were located in 25 of the 714 potential host trees. Light microscopy of sampled roots showed mycorrhizal fungi in 22 of the 25 sampled orchids. Phylogenetic analysis of ITS1-5.8S-ITS2 sequences yielded two Tulasnella clades. In four cases, plants were found to be associated with both clades. The difference between univariate and bivariate K functions was consistent with the random labeling null model at all spatial scales, indicating that trees hosting clades A and B of Tulasnella are not spatially segregated. The analysis of the inhomogenous K function showed that host trees are not clustered, suggesting no limitations to population-scale dispersal. χ(2) analysis of contingency tables showed that E. rhopalostele is more frequent on dead trees than expected. CONCLUSIONS: EPIDENDRUM RHOPALOSTELE establishes mycorrhizal associations with at least two different Tulasnella species. The analysis of the distribution patterns of this orchid suggests a microsite preference for dead trees and no seed dispersal limitation.