Significance of clinical-immunological patterns and diagnostic yield of biopsies in microscopic polyangiitis and granulomatosis with polyangiitis.

BACKGROUND: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). OBJECTIVES: To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. RESULTS: This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. CONCLUSIONS: The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.

Ocular involvement in adult and paediatric patients with monogenic autoinflammatory diseases: a Spanish multicentre retrospective study.

OBJECTIVES: Ophthalmologic involvement in monogenic autoinflammatory diseases has been explored mainly in paediatric patients. The aim of this study is to characterise ophthalmologic manifestations, therapeutic management and visual outcomes in a Spanish (UVESAI) cohort of adult/paediatric patients with monogenic autoinflammatory diseases. METHODS: Multicentre and retrospective study of patients with monogenic autoinflammatory diseases and ocular involvement. Eye manifestations, structural complications, treatments used and visual outcomes were analysed, and compared with previous studies. RESULTS: Forty-six patients (44/2 adults/children; 21/25 adult/paediatric-onset) with monogenic autoinflammatory diseases [cryopyrin associated periodic syndromes (n=13/28.3%), mainly Muckle-Wells syndrome (MWS) (n=11/24%); familial Mediterranean fever (FMF) (n=12/26%); TNF receptor-associated periodic syndrome (TRAPS); (n=9/20%); Blau syndrome (n=8/17%); hyperimmunoglobulin D syndrome (HIDS) (n=2/4.3%), deficiency of adenosine deaminase-2 and NLRC4-Autoinflammatory disease] (one each) were included. Conjunctivitis (n=26/56.5%) and uveitis (n=23/50%) were the most frequent ocular manifestations. Twelve (26.1%) patients developed structural complications, being cataracts (n=11/24%) and posterior synechiae (n=10/22%) the most frequent. Conjunctivitis predominated in TRAPS, FMF, MWS and HIDS (mainly in adults), and uveitis, in Blau syndrome. Seven (8%) eyes (all with uveitis) presented with impaired visual acuity. Local and systemic treatment led to good visual outcomes in most patients. Compared with previous studies mainly including paediatric patients, less severe ocular involvement was observed in our adult/paediatric cohort. CONCLUSIONS: Conjunctivitis was the most common ocular manifestation in our TRAPS, FMF, MWS and HIDS patients, and uveitis predominated in Blau syndrome. Severe eye complications and poor visual prognosis were associated with uveitis. Adults with monogenic autoinflammatory diseases seem to exhibit a less severe ophthalmologic presentation than paediatric patients.

Efficacy of canakinumab in a patient with adult-onset glucocorticoid-resistant periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, a polygenic or multifactorial condition, is the most frequent autoinflammatory disease in children. There is increasing evidence that some patients may have a disease onset during adulthood. With regard to PFAPA syndrome treatment, single medium-to-high doses of glucocorticoids during flares constitute the therapy of choice in children and adults, colchicine may be useful in some patients, and tonsillectomy has been reported of utility mainly in paediatric patients. Interleukin-1 (IL-1) blockers have been sporadically used with good response in glucocorticoid-resistant cases. We report a patient with an adult onset of glucocorticoid-resistant PFAPA syndrome and inconsistent response to colchicine and anakinra, who later achieved a complete and sustained response to canakinumab. Although canakinumab seems to be a good therapeutic option in paediatric and adult patients with refractory PFAPA syndrome, the best anti-IL-1 agent and the sequence of administration have to be still determined in well-designed clinical trials.

Atypical antipsychotics olanzapine and clozapine increase bone loss in female rats with experimental periodontitis.

BACKGROUND AND OBJECTIVES: Periodontitis is a highly prevalent disease in psychiatric patients, including those undergoing symptomatic treatment with second-generation antipsychotics. Some of these drugs, such as clozapine (CLO) and olanzapine (OLA), have prominent metabolic effects such as weight gain, hyperglycemia, and dyslipidemia, which are risk factors for periodontitis. In addition to the metabolic effects, there are reports of changes in salivary flow, gingival bleeding, and caries. In this context, we aimed to evaluate if the metabolic effects of OLA and CLO alter periodontal parameters in an animal model of periodontitis without the environmental and psychosocial biases inherent to human diseases. METHODS: In the first set of experiments, male and female adult Wistar rats received oral administration of CLO, OLA, or vehicle for 45 days. They were evaluated for body mass composition and weight gain, blood glucose parameters (fasting and glucose tolerance and insulin resistance tests), and lipid profile (HDL, total cholesterol, and triglycerides). In a second set of experiments, the same measurements were performed in female rats exposed to the antipsychotics for 45 days and ligature-induced periodontitis on the 30th day of treatment. Macroscopic measurements of exposed roots, microtomography in the furcation region of the first molar, and histological evaluation of the region between the first and second molars were evaluated to assess bone loss. Additionally, gingival measurements of myeloperoxidase activity and pro-inflammatory cytokine TNF-α were made. RESULTS: Only females exposed to OLA had more significant weight gain than controls. They also exhibited differences in glucose metabolism. Ligature-induced periodontitis produced intense bone retraction without changing the density of the remaining structures. The bone loss was even higher in rats with periodontitis treated with OLA or CLO and was accompanied by a local increase in TNF-α caused by CLO. These animals, however, did not exhibit the same metabolic impairments observed for animals without periodontitis. CONCLUSION: The use of clozapine and olanzapine may be a risk factor for periodontal disease, independent of systemic metabolic alterations.

Effects of infrared light laser therapy on in vivo and in vitro periodontitis models.

BACKGROUND: This study evaluated the effects of infrared light laser therapy (ILLT) on ligature-induced periodontitis in rats using micro-computed tomography (micro-CT), histology, fibroblast migration, and viability analysis. METHODS: Forty-eight rats were randomly distributed into three groups: control (no periodontitis), PDC (periodontitis without laser therapy), and PD+L (periodontitis with laser therapy). Periodontitis was induced by ligature placement for 4 weeks. The 12-week-old rats (baseline) were subjected to laser treatment and euthanized 30 days after. After treatment, the mandibular first molars were prepared for micro-CT scanning, and histological sections were assessed as to the cementoenamel junction, alveolar bone crest, and polymorphonuclear (PMN) cell infiltration. In vitro assays were carried out to examine NIH/3T3 fibroblast viability after laser therapy. RESULTS: Migration and cell viability assays revealed that the ILLT maintained fibroblast cell viability with 4 J/cm2 , reaching 100% healing. The control group (at baseline and 30 days) presented a statistically significant difference from the PDC group at 30 days in terms of distance from the cementoenamel junction to the alveolar bone crest (CEJ-ABC). The PD+L group showed a statistically substantial difference from the PDC group at 30 days in terms of trabecular thickness (Tb.Th), degree of anisotropy (DA), and closed porosity percentage (Po%). CONCLUSION: ILLT seemed to preserve the bone structure in the in vivo periodontitis induction model at 30 days and did not reduce cell viability or increase fibroblast migration in vitro. The ILLT provides positive effects on mandibular bone microstructure.

COVID-19: presentación clínica en pacientes hospitalizados en el Instituto de Medicina Tropical "Pedro Kourí" / COVID-19: clinical presentation in patients admitted to Pedro Kourí Tropical Medicine Institute

. Introducción: Con los primeros casos de COVID-19 en Cuba era necesario el reconocimiento temprano de los pacientes con riesgo de evolucionar hacia formas graves de la enfermedad. Objetivo: Describir el comportamiento clínico de la COVID-19 en pacientes hospitalizados en el Instituto de Medicina Tropical "Pedro Kourí" e identificar factores asociados a la gravedad. Métodos: Se presentaron los primeros 73 casos de COVID-19 hospitalizados en el Instituto de Medicina Tropical Pedro Kourí desde el 11 de marzo al 5 mayo de 2020. Los pacientes se clasificaron en dos grupos: graves y con enfermedad ligera. Se compararon variables clínicas, demográficas, de laboratorio e imagenológicas en el momento del ingreso, y su posible asociación con la gravedad de la enfermedad. Resultados: Hubo siete pacientes graves (9,6 por ciento), cinco fallecieron. La edad > 60 años, tener más de una comorbilidad, hipertensión arterial y asma bronquial, fueron más frecuentes en pacientes graves. La fiebre más de seis días (p= 0,00), disnea (p= 0,00), presencia de estertores húmedos (p= 0,00), frecuencia respiratoria > 24/min (p= 0,00) y valores de linfocitos < 0,8 x109/L (p= 0,00), de ferritina > 500µg/L (p =0,00), proteína C reactiva ( 10μg/L (p= 0,01) y LDH ( 500 U/L (p= 0,01) se relacionaron con la gravedad. El 18,2 por ciento de las radiografías de tórax mostró alteraciones, con predominio de focos de condensación inflamatoria bilateral. Las complicaciones más frecuentes fueron: distrés respiratorio, choque, sepsis bacteriana y afecciones cardíacas. Conclusiones: Existen características clínicas y de laboratorio, identificables al ingreso, que están relacionadas con la gravedad de la enfermedad; lo que puede ser útil para la estratificación del riesgo y el manejo adecuado de los pacientes(AU)

Introduction: Upon appearance of the first COVID-19 cases in Cuba, early identification of patients at risk of developing severe forms of the disease became a necessity. Objective: Describe the clinical behavior of COVID-19 in patients admitted to Pedro Kourí Tropical Medicine Institute and identify factors associated to severity. Methods: A presentation was made of the first 73 COVID-19 cases admitted to Pedro Kourí Tropical Medicine Institute from 11 March to 5 May 2020. The patients were divided into two groups: severe and mild disease. A comparison was made of clinical, demographic, laboratory and imaging variables at admission, and their possible association to disease severity. Results: Seven patients (9.6%) were critically ill; five died. Age > 60 years, more than one comorbidity, arterial hypertension and bronchial asthma were more common among critical patients. Fever for more than six days (p= 0.00), dyspnea (p= 0.00), presence of humid stertors (p= 0.00), respiratory rate > 24/min (p= 0.00) and lymphocytes < 0.8 x109/l (p= 0.00), ferritin > 500 µg/L (p =0.00), C-reactive protein 10 μg/l (p= 0.01) and LDH 500 U/l (p= 0.01) were related to disease severity. 18.2 percent of the chest radiographs showed alterations, with a predominance of bilateral foci of inflammatory condensation. The most common complications were respiratory distress, shock, bacterial sepsis and heart disorders. Conclusions: Some clinical and laboratory characteristics identifiable at admission may be associated to disease severity, which makes them useful for risk stratification and the appropriate management of patients(AU)

Periodontal status, vascular reactivity, and platelet aggregation changes in rats submitted to hypercholesterolemic diet and periodontitis.

BACKGROUND AND OBJECTIVES: Periodontitis can corroborate with development and progression of atherosclerosis and a possible bidirectional interaction between both pathologies has been hypothesized. The aim of this work was to study the interactions between diet-induced hypercholesterolemia and ligature-induced periodontitis in Wistar rats submitted to both conditions. MATERIAL AND METHODS: Animals were divided into four experimental groups: C (control: standard diet without periodontitis), Perio (periodontitis plus standard diet), HC (high cholesterol diet without periodontitis), and HC + Perio (high cholesterol diet plus periodontitis). The diets were offered for 45 days and a silk ligature was applied in the lower first molars of Perio and HC-Perio animals on day 34 and maintained for 11 days until euthanasia. The mandibles were excised, and alveolar bone loss was determined by macroscopic and micro-tomographic (µ-CT) imaging. Blood samples were obtained, and platelet aggregation was induced in plasma rich in platelets by adenosine diphosphate (ADP) and collagen. Endothelium-dependent vascular reactivity and protein expression of endothelial (eNOS), phosphorylated endothelial (peNOS), and inducible (iNOS) nitric oxide synthases were evaluated in aorta samples. RESULTS: The HC diet combined with periodontitis (HC + Perio group) was associated with an increased alveolar bone loss, when compared to the other groups. Both in Perio and HC groups, platelet aggregation induced by ADP or collagen was increased, while maximum aortic relaxation induced by acetylcholine was decreased. Periodontitis or HC diet alone decreased the expression of peNOS and HC diet increased the expression of iNOS. In contrast, no additive or synergistic effects were found in vascular reactivity or in platelet aggregation when the two conditions were associated (HC + Perio group). CONCLUSION: Hypercholesterolemia accelerated the process of bone loss induced by periodontitis while a high cholesterol diet or periodontitis individually increased platelet aggregation and vascular reactivity in rats without additive or synergistic effects, when associated.

Instituições de Longa Permanência para Idosos no Brasil: revisão integrativa da literatura / Long-stay Institutions in Brasil: an integrative literature review / Instituciones de largo plazo para ancianos en Brasil: una revisión integradora de literatura

Objetivou-se levantar e analisar a produção científica acerca do delineamento dos trabalhos publicados e temas estudados sobre as instituições de longa permanência para idosos no Brasil, produção essa arrolada no LILACS, MEDLINE, BDENF e SciELO no período de 2013 a 2017. O corpus constitui-se por 88 artigos. Nota-se um número insipiente de pesquisas com intervenções, visto que os pesquisadores ainda buscam descrever o perfil dos idosos institucionalizados, segundo critérios de saúde e doença.

It was aimed to review the literature about Brazilian nursing homes for seniors published at LILACS, MEDLINE, BDENF and SciELO between 2013 and 2017. The corpus consists of 90 articles. There is an incipient amount of papers about intervention research, as long as the researchers still seek to describe the profile of the resident seniors, according to health and disease criteria.

El objetivo fue encuestar y analizar la producción científica sobre la delineación de los trabajos publicados y los temas estudiados sobre las instituciones de atención a largo plazo para ancianos en Brasil. El corpus consta de 88 artículos. Existe un número incipiente de investigaciones con intervenciones, ya que los investigadores todavía buscan describir el perfil de los ancianos institucionalizados, de acuerdo con los criterios de salud y enfermedad.

Estado redox en pacientes infectados por VIH/sida con insuficiencia renal crónica sometidos a hemodiálisis / The redox state of VIH/AIDS patients suffering chronic renal failure and undergoing hemodyalisis

Introducción: el balance redox alterado en el curso de la insuficiencia renal crónica ha sido considerado un factor contribuyente a la morbilidad y mortalidad de la enfermedad y un factor asociado a la progresión de la infección por sida.Objetivo: valorar el estado redox en pacientes infectados por VIH con insuficiencia renal crónica que requirieron hemodiálisis.Métodos: se realizó un estudio de casos y controles en 20 pacientes VIH/sida con insuficiencia renal crónica y 40 individuos aparentemente sanos. Se realizaron determinaciones de malonildialdehído, glutatión, superóxido dismutasa, catalasa, productos avanzados de la oxidación de proteínas, hidroperóxidos y potencial de peroxidación, conjuntamente con los marcadores de progresión: conteo de linfocitos T CD4+ y carga viral y una serie de determinaciones hemoquímicas y hematológicas. El análisis se realizó antes, a los 30 min y a los 240 min del tratamiento dialítico. Estadísticamente se verificaron los supuestos de igualdad de varianza y normalidad de las variables, y en dependencia se aplicó una prueba paramétrica o no paramétrica. El resultado fue significativo para p< 0,05.Resultados: los indicadores del estado redox se encontraron alterados en los pacientes estudiados con respecto al grupo supuestamente sano antes de la hemodiálisis. Se mostró un valor mayor significativo (p< 0,05) de los índices malonildialdehído, productos avanzados de la oxidación de proteínas, superóxido dismutasa, y un valor menor de catalasa y glutatión a los 240 min de realizada la diálisis, con la excepción de los hidroperóxidos que no mostraron cambios. La carga viral plasmática disminuyó de manera significativa en el proceso.Conclusiones: los resultados sugieren que el proceso dialítico en este tipo de pacientes favorece el estrés oxidativo, conjuntamente con una disminución de la carga viral plasmática. El estudio aporta valor metodológico en el manejo de estos pacientes y en la búsqueda por mejorar su calidad de vida

Impacto de la prohibición de fumar en espacios cerrados sobre los ingresos por infarto agudo de miocardio en Uruguay / The impact of banning indoor smoking on hospital admissions for acute myocardial infarction

Introducción: la exposición al humo de tabaco ambiental aumenta 31 por ciento el riesgo de infarto entre no fumadores. En países desarrollados se observó reducción de los ingresos por infartoagudo de miocardio al prohibirse fumar en espacios cerrados. El presente estudio evaluó el impacto de la prohibición de fumar sobre el infarto agudo de miocardio en Uruguay, el primer país libre de humo de tabaco en las Américas. Material y método: se realizó un estudio ecológico comparando los ingresos por infarto en los 24 meses anteriores y posteriores a marzo de 2006 (fecha de la aprobación de la normativa que estableció la prohibición de fumar en espacios cerrados de uso público). Se analizaron retrospectivamente las historias clínicas de los pacientes residentes en el país que tuvieran infarto de miocardio como diagnóstico principal de ingreso. El análisis estadístico se realizó mediante el test de chi cuadrado. Resultados: en las 37 instituciones participantes ingresaron 7.949 pacientes (66,4 ± 12,6 años, 35,1 por ciento mujeres), 4.346 en los dos años previos a las medidas y 3.603 en los dos años siguientes, lo que implicó una reducción de 17,1 por ciento. Hubo mayor reducción a menor edad de los pacientes: <45 años: 38,5 por ciento; 45 a 64 años: 14,8 por ciento; > 65 años: 16,9 por ciento, p < 0,05. Los viernes y sábados los ingresos descendieron 24,2 por ciento, de domingos a jueves 14,3 por ciento (p < 0,05). En los centros privados hubo 22,0 por ciento de reducción, en los públicos 6,3 por ciento, p < 0,05. Conclusiones: la prohibición de fumar en espacios cerrados se asoció a una disminución en los ingresos por infarto agudo de miocardio en nuestro país, siendo este efecto particularmente importante entre los más jóvenes. El beneficio predominó viernes y sábado yfue menor entre quienes se asisten en el sector público.

Introduction: exposure to environmental tobacco smoke increases the risk for infarction in 31 percent among nonsmokers.A decrease in hospital admission due to acute myocardial infarction was noticed in developed countries when indoor smoking was banned. The present studyanalyzed the impact of smoking bans on acute myocardial infarction in Uruguay, the first tobacco- smoke-freecountryin the Americas. Method: we conducted an ecological study that compared hospital admissions for infarction in the 24 months prior to March 2006 to admissions during the 24 months subsequent to that date (date when the anti-smoking regulation was passed, banning indoor public spaces). We retrospectively analyzed the medical records of patients residing in the country whose main diagnosis for admission was myocardial infarction. The statistic analysis was made by using the chi square test. Results: 7,949 patients were admitted in the 37 participating institutions (66,4 ± 12,6 years old, 35,1 percent women), 4,346 were admitted over the two year period prior to the new measures, and 3,603 during the two-year period subsequent to the prohibition, what implied a 17.1 percent drop. The younger the patients, the greater the drop: <45 years old: 38,5 percent; 45 to 64 years old: 14,8 percent; > 65 years old: 16,9 percent, p < 0,05. Admissions decreased by 24.2 percent on Fridays and Saturdays, and 14.3 percent from Sundays toThursdays (p < 0,05). Decrease was 22.0 percent in private institutions and 6.3 percent in public institutions, p < 0,05. Conclusions: Indoor smoking bans were associated to a decrease in hospital admission for acute myocardial infarction in our country, being this effect particularly important in the younger people. The benefit of this new legislation was more important on Fridays and Saturday and lower in those patients seen in the public sector.

Introdução: a exposição ao fumo de tabaco ambiental aumenta 31 por cento o risco de infarto entre os não fumantes. Nos países desenvolvidos observou-se uma diminuição das internações por infarto de miocárdio depois da proibição de fumar em espaços fechados. Este estudo faz uma avaliação do impacto da proibição de fumar sobre o infarto de miocárdio no Uruguai, o primeiro país livre de fumo de tabaco nas Américas. Material e método: fez-se um estudo ecológico comparando as internações por infarto de miocárdio nos 24 meses anteriores e posteriores a março de 2006, data da aprovação da legislação que proíbe fumar em espaços públicos fechados. Fez-se uma análise retrospectiva dos prontuários médicos dos pacientes residentes no Uruguaique apresentaram infarto como diagnóstico principal; os dados foram analisados utilizando o teste de Qui quadrado Resultados: Nas 37 instituições incluídas no estudo foram internados 7.949 pacientes (66,4 ± 12,6 anos, 35,1 por cento mulheres), 4.346 nos anos anteriores às medidas de proibição e 3.603 nos dois anos seguintes, com uma redução de 17,1 por cento. A redução foi maior nos pacientes mais jovens: <45 anos: 38,5 por cento; 45 a 64 anos: 14,8 por cento; > 65 anos: 16,9 por cento, p < 0,05. As internações nas sextas-feiras e sábados caíram 24,2 por cento, e de domingo a quinta-feira 14,3 por cento (p < 0,05). Nas instituições de assistência médica privada a redução foi de 22,0 por cento e de 6,3 por cento, p < 0,05 nos públicos. Conclusões: a proibição de fumar em espaços públicos fechados mostrou uma associação com uma redução das internações por infarto agudo de miocárdio observando-se um impacto especial em pacientes mais jovens. Este benefício foi predominante nas sextas-feiras e sábados e foi menor na população atendida no setor público.