Limited Antineutrophil Cytoplasmic Antibodies (ANCA)-Negative Granulomatosis With Polyangiitis: Successful Response to Rituximab

Granulomatosis with polyangiitis (GPA), a systemic vasculitis, is commonly characterized by the presence of antineutrophil cytoplasmic antibodies (ANCA). However, a subset of patients with limited disease may exhibit ANCA negativity. In this article, we report the case of a 40-year-old female diagnosed with GPA with intolerance to methotrexate titration and glucocorticoid therapy, leading to the initiation of rituximab treatment. Subsequently, the patient exhibited sustained clinical, laboratory, and radiological improvement. The identification of limited GPA has important therapeutic implications as the effectiveness of the medical treatment in ANCA-negative GPA may differ. Rituximab has emerged as an optimal treatment, irrespective of ANCA status, offering prolonged responses and a favorable tolerance profile in these patients.info:eu-repo/semantics/publishedVersio

Non-Vitamin K Oral Anticoagulants Assessment in High Risk of Bleeding Patients with Non-Valvular Atrial Fibrillation

Atrial fibrillation (AF) is commonly associated with advanced age and the presence of multiple, concomitant acute and chronic health conditions, placing this population at high risk for serious therapeutic side effects. Nonvitamin K antagonist oral anticoagulants (NOACs) are increasingly used for stroke prevention in patients with atrial fibrillation. The purpose of this study was to investigate the effectiveness and safety of NOAC in a group at high risk of bleeding complications, in a real-world setting. We conducted a retrospective analysis of a high-risk cohort of 418 patients (pts) followed-up in our anticoagulation unit; data on patient characteristics, anticoagulation treatment, and bleeding and thrombotic complications were evaluated. The population had a median age of 77.8 ± 10.3 years and the mean CHA2DS2-VASc score was 3.85 (SD ± 1.4). Overall, 289 (69.1%) were ≥75 years old. During a mean follow-up time of 51.2 ± 35.7 months, we observed a rate of any bleeding of 7, a clinically relevant non-major bleeding rate of 4.8, a major bleeding rate of 2.2, a stroke rate of 1.6, and a rate of thrombotic events of 0.28 per 100 patient-years. There were 59 hospitalizations due to any cause (14.1%) and 36 (8.6%) deaths (one due to ischemic stroke). A structured follow-up, with judicious prescribing and drug compliance, may contribute to preventing potential complicationsinfo:eu-repo/semantics/publishedVersio

Estrogen receptor, progesterone receptor, and bcl-2 are markers with prognostic significance in CIN III

There are no known biological markers or technologies to predict the natural history of an individual CIN III. The probability of progression is considered greater with the persistence of high-risk human papillomavirus (HPV) infection and age. p53 polymorphism has been associated with cervical carcinogenesis. Hormone-induced cervical cancer is mediated by estrogen receptor (ER) and progesterone receptor (PR). In cervical cancer, increased bcl-2 and Bax immunoreactivity is generally associated with a better prognosis. The purpose of this study was to evaluate the value of HPV 16 and HPV 18 typing and p53 codon polymorphism genotyping by polymerase chain reaction and ER, PR, bcl-2, and Bax expression by immunohistochemistry in predicting the CIN III clinical behavior of CIN III lesions. We studied the expression of these prognostic factors in the CIN III adjacent to squamous cell microinvasive carcinomas of the cervix (MIC) from 29 patients with FIGO stage IA1 cervical cancer and in 25 patients with CIN III and no documented focus of invasion. In the MIC group, only the CIN III was considered at least 2 mm away from the microinvasive complex. The ER, PR, bcl-2, and Bax immunoreactivity was scored as positive (>10% staining cells) and negative (<10% staining cells). No significant difference was observed between MIC and CIN III group concerning HPV infection and p53 polymorphism. The ER, PR, bcl-2, and Bax immunohistochemical expression was stronger and more frequent in the CIN III group. After multivariable analysis, coexpression of ER, PR, and bcl-2 was the only independent factor in defining low risk of progression for CIN III. Our study suggests that coexpression of ER, PR, and bcl-2 may be a useful tool in identifying the CIN III lesions with low risk of progression to cervical cance

Use of Nitroglycerin in the Active Phase of Tilt Testing: Is There a Difference in Elderly Patients?

Está demonstrado o papel do teste de inclinação na avaliação de doentes com síncope de causa não esclarecida, sendo utilizado como a técnica gold standard para o diagnóstico da síncope neurocardiogénica, em particular com o recurso a agentes provocativos farmacológicos de modo a melhorar a acuidade diagnóstica. A estimulação com nitroglicerina sub-lingual é, regra geral, bem tolerada e permite aumentar a sensibilidade do teste reduzindo a sua duração. Neste sentido, tem-se verificado também o alargamento da sua aplicação em doentes idosos. Objectivos: Avaliar, numa população referenciada por síncope de etiologia desconhecida, a utilidade do teste de inclinação com recurso a nitroglicerina sub-lingual e comparar o tipo de respostas obtidas nos doentes idosos com o dos restantes doentes. Métodos: Estudámos 158 doentes submetidos a teste de inclinação com utilização de nitroglicerina como agente provocativo. Foram considerados doentes com idade <65 anos (Grupo A, n=74) e ≥65 anos (Grupo B, n=84). O teste de inclinação foi efectuado segundo o protocolo “italiano”, sob monitorização contínua do electrocardiograma e da tensão arterial (Task Force Monitor; CNSystems). Foram incluídos somente doentes assintomáticos na fase passiva do teste. O teste foi considerado positivo para resposta neurocardiogénica quando houve reprodução da sintomatologia acompanhada de bradicardia e/ou hipotensão arterial e as respostas foram definidas como cardio-inibitória, vasodepressora ou mista. Uma descida gradual e paralela da tensão arterial após administração de nitroglicerina seguida de síncope foi considerada como resposta exagerada aos nitratos. Resultados: Não se verificam diferenças na distribuição por sexos entre os grupos. O teste de inclinação foi positivo em 57% do Grupo A e 51% do Grupo B (p=NS), tendo ocorrido resposta exagerada aos nitratos em 11% e 16%, respectivamente (p=NS). Relativamente ao tipo de respostas neurocardiogénicas, as vasodepressoras foram mais frequentes no Grupo B (53% versus 24%; p=0,001) e as mistas tendencialmente mais frequentes no Grupo A (59% versus 40%; p=0,07), sem diferenças significativas no que se refere à resposta do tipo cardio-inibitória (17% nos Grupo A versus 7% no Grupo B; p=NS). Conclusões: Numa população com síncope de etiologia não conhecida, o teste de inclinação potenciado pela nitroglicerina: a) contribui de modo significativo para o esclarecimento diagnóstico com utilidade idêntica em idosos e nos restantes doentes. B) associa-se a maior incidência de resposta neurocardiogénica vasodepressora nos idosos embora com uma taxa semelhante de respostas exageradas aos nitratos

O Treino de Ortostatismo (Tilt Training) Aumenta a Reserva Vasoconstritora em Doentes com Síncope Reflexa Neurocardiogénica

Neurocardiogenic syncope (NCS) is a common clinical entity resulting from an excessive reflex autonomic response, particularly during orthostatism. Treatment options are controversial and of limited effectiveness. Tilt training (TT) is a promising option to treat these patients. However, its mechanism of action and clinical impact remain unclear. OBJECTIVE: To characterize hemodynamic and autonomic responses during a TT program in patients with NCS refractory to conventional measures. METHODS: We studied 28 patients (50% male, mean age 41±14 years) without structural heart disease, with NCS documented by tilt testing. The TT program included 9 tilt sessions (3 times a week, 30 min) (60° - 6 sessions, 70° - 3 sessions), under ECG and blood pressure monitoring combined with home orthostatic self-training and 10° head-up during sleep. Systolic volume, cardiac output, total peripheral resistance, baroreflex sensitivity and heart-rate variability were computed. Patients were reassessed at 1 month and every 6 months for a maximum of 36 months (24±12 months). RESULTS: Over the course of the TT program there was a significant increase in total peripheral resistance (1485±225 vs. 1591±187 dyn·s·cm(-5), p<0.05), with a decrease in standard deviation (206±60 vs. 150±42, p<0.05). During follow-up, syncope recurred in five patients (19%), with a significant reduction in the number of episodes (4.0±3.2/patient in the 12 months before TT vs. 1.4±0.8/patient post-TT, p<0.05). CONCLUSION: In refractory NCS, TT may be an effective therapeutic option, with long-term benefits. These results appear to be due to an increase in vasoconstrictor reserve combined with a reduction in its variance

Diurnal variability of inner-shelf circulation in the lee of a cape under upwelling conditions.

The nearshore circulation in the lee of a cape under upwelling conditions was studied using in-situ data from 3 consecutive summers (2006–2008). Focus was given to a period between 20 July and 04 August 2006 to study the diurnal variability of the cross-shelf circulation. This period was chosen because it had a steady upwellingfavourable wind condition modulated by a diurnal cycle much similar to sea breeze. The daily variability of the observed cross-shelf circulation consisted of three distinct periods: a morning period with a 3-layer vertical structure with onshore velocities at mid-depth, a mid-day period where the flow is reversed and has a 2-layer structure with onshore velocities at the surface and offshore flow below, and, lastly, in the evening, a 2-layer period with intensified offshore velocities at the surface and onshore flow at the bottom. The observed cross-shelf circulation showed a peculiar vertical shape and diurnal variability different from several other systems described in literature. We hypothesize that the flow reversal of the cross-shelf circulation results as a response to the rapid change of the wind magnitude and direction at mid-day with the presence of the cape north of the mooring site influencing this response. A numerical modelling experiment exclusively forced by winds simulated successfully most of the circulation at the ADCP site, especially the mid-day reversal and the evening's upwelling-type structure. This supports the hypothesis that the cross-shelf circulation at diurnal timescales is mostly wind-driven. By analysing the 3D circulation in the vicinity of Cape Sines we came to the conclusion that the diurnal variability of the wind and the flow interaction with topography are responsible for the circulation variability at the ADCP site, though only a small region in the south of the cape showed a similar diurnal variability. The fact that the wind diurnally undergoes relaxation and intensification strongly affects the circulation, promoting superficial onshore flows in the leeside of Cape Sines. Despite the small-scale nature of the observed cross-shelf circulation, onshore flows as the ones described in this study can be particularly helpful to understand the transport and settlement of larvae in this region and in other regions with similar topography and wind characteristics.We thank D. Jacinto and T. Silva for help during field work and the Port of Sines Authority (APS) for providing oceanographic and meteorological data. Financial support was provided by FCT (POCI/ MAR/57630/2004; PTDC/BIA-BEC/103734/2008 and PEst-OE/ MAR/UIO199/2011). The simulations were preformed in the computational facilities provided under FCT contract RECI/GEO-MET/0380/ 2012. Luísa Lamas was funded by the FCT under a Ph.D. grant (SFRH/ BD/69533/2010)