Acute hemorrhagic edema of young children (cockade purpura and edema): a case series and systematic review

BACKGROUND: Acute hemorrhagic edema is an uncommon leukocytoclastic small-vessel vasculitis of young children. OBJECTIVE: To determine clinical features and outcome of acute hemorrhagic edema of young children. METHODS: Seven new cases are reported. A search of the literature revealed 287 published cases. RESULTS: The 294 children (boys, 67%) ranged in age between 2 and 60 months (median, 11 months) and were in good general condition. In 195 children the disease developed after a simple acute infection. The exanthemata included large, round, red to purpuric plaques predominantly over the cheeks, ears, and extremities and mostly tender edema of the distal extremities, ears, and face. Involvement of body systems other than skin was rare. The children recovered spontaneously without sequelae. LIMITATIONS: Results of this review must be viewed with an understanding of the limitations of the analysis process, which incorporated data exclusively from single case reports or case series. CONCLUSIONS: Acute hemorrhagic edema of young children is a very benign vasculitis. Physicians might rapidly develop the skills necessary to diagnose this condition.

Outcome of acute stroke patients without visible occlusion on early arteriography

BACKGROUND: The aim of this study was to determine the clinical and radiological outcome of acute stroke patients who had no vessel occlusion on arteriography and to define predictors of clinical outcome. METHODS: We analyzed clinical and radiological data of stroke patients whose arteriography performed within 6 hours of symptom onset did not visualize any vessel occlusion. RESULTS: Twenty-eight of 283 consecutive patients (10%) who underwent arteriography with the intention to perform intraarterial thrombolysis did not show any arterial occlusion. Their median baseline National Institutes of Health Stroke Scale (NIHSS) score was 7. Time from symptom onset to arteriography ranged from 115 to 315 minutes; on average, it was 226 minutes. Presumed stroke cause was cardiac embolism in 11 patients (39%), small artery disease in 6 (21%), coronary angiography in 1 (4%), and undetermined in 10 patients (36%). After 3 months, modified Rankin Scale score (mRS) was < or =2 in 21 patients (75%), indicating a favorable outcome. Six patients (21%) had a poor outcome (mRS 3 or 4) and 1 patient (4%) had a myocardial infarction and died. Twenty-seven patients had follow-up brain imaging. It was normal in 5, showed a lacunar lesion in 8, a striatocapsular infarct in 2, a small or medium-sized anterior circulation infarct in 6, multiple small anterior circulation infarcts in 2, and multiple posterior circulation infarcts in 4. No predictors of clinical outcome were identified. CONCLUSIONS: Most acute stroke patients with normal early arteriography show infarcts on brain imaging; however, clinical outcome is usually favorable.

[Systemic ANCA-associated vasculitis--diagnosis and therapy]

ANCA-associated vasculitis represents a group of small-vessel vasculitides, including Wegener's granulomatosis, microscopic polyangiitis and the Churg-Strauss-syndrome. These diseases affect mainly small arteries, venules and capillaries, showing a lack of immunocomplex formation on immunohistology, the so-called "pauci-immune" vasculitis. Nevertheless, Anti-Neutrophil Cytoplasmatic Autoantibodies (ANCA's) are pathogenic for this type of disease. In spite of important advances in technical diagnostic tools, careful medical history and clinical examinations often give the clues for the correct diagnosis. Recent collaborative therapeutic studies have lead to therapeutic schemas that are much more adapted to the individual disease state. Besides the acute and sometimes life-threatening form of ANCA-vasculitis, chronic disease and relapses become more important in clinical practice. Thus, therapeutic efficacy must be outweighed against long-term toxicity to make the right choice for therapeutic intervention in ANCA-associated vasculitis.

Complete arterial revascularization in multivessel coronary artery disease with 2 conduits (skeletonized grafts and T grafts)

BACKGROUND: Complete arterial CABG is a surgical option to improve long-term results in the treatment of coronary artery disease (CAD). Harvesting of multiple arterial grafts is commonly associated with prolonged operating times and increased trauma. By use of new operative techniques (skeletonized grafts and the T-graft approach), CABG in multivessel CAD is now possible with only 2 grafts. We present our experience in the use of these techniques on a routine basis. METHODS AND RESULTS: Between March 1996 and September 1999, 490 patients (aged 61+/-9 years, 20% female) underwent complete arterial CABG. Left ventricular ejection fraction ranged from 15% to 85% (mean 59+/-15%). Triple-vessel disease was present in 88% of the patients. The incidence of diabetes mellitus was 32% (14% insulin dependent). Either both internal thoracic arteries (ITAs) (23%) or the left ITA and radial artery (77%) were used as conduits. In 85% of the patients, a T graft was created. Mean operating time was 198+/-46 minutes; bypass time, 82+/-25 minutes; and ischemic time, 58+/-22 minutes. Two to 7 (mean 4.1+/-0.9) anastomoses were performed per patient. Perioperative intra-aortic balloon pump was necessary in 12 patients (2.4%). The rate of perioperative myocardial infarction was 1.2%. Sternal complications occurred in 1. 0%, and in-hospital mortality was 2.2%. Postoperative coronary angiography in 172 patients (35%) documented excellent patency rates (left ITA 98.3%, right ITA 96.5%, and radial artery 96.6%). CONCLUSIONS: Complete arterial revascularization in multivessel CAD is possible with the use of only 2 grafts with good perioperative results. This approach allows for complete arterial CABG on a routine basis.

Coronary artery disease is common in asymptomatic patients with signs of myocardial ischemia

BACKGROUND: The incidence of coronary artery disease (CAD) in totally asymptomatic patients with myocardial ischemia during stress testing is unknown. METHODS: 54 patients with asymptomatic myocardial ischemia participated in the Swiss Interventional Study on Silent Ischemia type I (SWISSI I). Asymptomatic myocardial ischemia was verified by bicycle ergometry and stress imaging (echocardiography or scintigraphy). Findings from coronary angiographies in the course of the study constituted the main outcome. RESULTS: Of the 54 study participants, 29 patients (53.7%) underwent coronary angiography. CAD was found in 27 of 29 patients (93.1%). In those 27 patients with CAD, 9 patients (33.3%) suffered from single vessel disease, 9 patients (33.3%) from two vessel disease, and 9 patients (33.3%) from triple vessel disease. Two patients showed left main coronary artery stenosis. CONCLUSION: This study shows a high incidence of relevant CAD among totally asymptomatic patients with myocardial ischemia during stress testing. Previously healthy subjects with exercise-induced ST-segment depression at check-up examinations, even if asymptomatic, should have further diagnostic evaluation.

Phenotypic associations of Crohn's disease with antibodies to flagellins A4-Fla2 and Fla-X, ASCA, p-ANCA, PAB, and NOD2 mutations in a Swiss Cohort

BACKGROUND: Distinct Crohn's disease (CD) phenotypes correlate with antibody reactivity to microbial antigens. We examined the association between antibody response to 2 new flagellins called A4-Fla2 and Fla-X, anti-Saccharomyces cerevisiae antibodies (ASCA), anti-neutrophil cytoplasmic antibodies (p-ANCA), anti-pancreas antibodies (PAB), NOD2 mutations (R702W, G908R, and L1007fsinsC), and clinical CD phenotypes (according to Vienna criteria). METHODS: All the above-mentioned antibodies as well as NOD2 mutations were determined in 252 CD patients, 53 with ulcerative colitis (UC), and 43 healthy controls (HC) and correlated with clinical data. RESULTS: A seroreactivity for A4-Fla2/Fla-X/ASCA/p-ANCA/PAB (in percent) was found in 59/57/62/12/22 of CD patients, 6/6/4/51/0 of UC patients, and 0/2/5/0/0 of healthy controls. CD behavior: 37% B1, 36% B2, and 27% B3. In multivariate logistic regression, antibodies to A4-Fla2, Fla-X, and ASCA were significantly associated with stricturing phenotype (P = 0.027, P = 0.041, P < 0.001), negative associations were found with inflammatory phenotype (P = 0.001, P = 0.005, P < 0.001). Antibodies to A4-Fla2, Fla-X, ASCA, and NOD2 mutations were significantly associated with small bowel disease (P = 0.013, P = 0.01, P < 0.001, P = 0.04), whereas ASCA was correlated with fistulizing disease (P = 0.007), and small bowel surgery (P = 0.009). Multiple antibody responses against microbial antigens were associated with stricturing (P < 0.001), fistulizing disease (P = 0.002), and small bowel surgery (P = 0.002). CONCLUSIONS: Anti-flagellin antibodies and ASCA are strongly associated with complicated CD phenotypes. CD patients with serum reactivity against multiple microbes have the greatest frequency of strictures, perforations, and small bowel surgery. Further prospective longitudinal studies are needed to show that antibody-based risk stratification improves the clinical outcome of CD patients.

Abnormal small airways function in children with mild asthma

BACKGROUND Small airways disease is a hallmark in adults with persistent asthma, but little is known about small airways function in children with mild asthma and normal spirometry. We assessed ventilation heterogeneity, a marker of small airways function, with an easy tidal breath single-breath washout (SBW) technique in school-aged children with mild asthma and normal FEV1 and healthy age-matched control subjects. METHODS The primary outcome was the double-tracer gas phase III slope (SDTG), an index of ventilation heterogeneity in acinar airways derived from the tidal double-tracer gas SBW test. The second outcome was the nitrogen phase III slope (SN2), an index of global ventilation heterogeneity derived from the tidal nitrogen SBW test using pure oxygen. Triplicate SBW and spirometry tests were performed in healthy children (n = 35) and children with asthma (n = 31) at baseline and in children with asthma after bronchodilation. RESULTS Acinar (SDTG) but not global (SN2) ventilation heterogeneity was significantly increased in asthma despite normal FEV1. Of the 31 children with asthma, abnormal results were found for SDTG (≤ -2 z scores) in 11; forced expiratory flow, midexpiratory phase (FEF25%-75%) in three; and FEV1 in zero. After bronchodilation, SDTG, SN2, FEF25%-75%, and FEV1 significantly changed (mean [95% CI] change from baseline, 36% [15%-56%], 38% [18%-58%], 17% [9-25%], and 6% [3%-9%], respectively). CONCLUSIONS Abnormal acinar ventilation heterogeneity in one-third of the children suggests that small airways disease may be present despite rare and mild asthma symptoms and normal spirometry. The easy tidal SBW technique has considerable potential as a clinical and research outcome in children with asthma.

Association of biomarkers of lipid modification with functional and morphological indices of coronary stenosis severity in stable coronary artery disease

Biomarkers of blood lipid modification and oxidative stress have been associated with increased cardiovascular morbidity. We sought to determine whether these biomarkers were related to functional indices of stenosis severity among patients with stable coronary artery disease. We studied 197 consecutive patients with stable coronary artery disease due to single vessel disease. Fractional flow reserve (FFR) ≤ 0.80 was assessed as index of a functionally significant lesion. Serum levels of secretory phospholipase A2 (sPLA2) activity, secretory phospholipase A2 type IIA (sPLA2-IIA), myeloperoxydase (MPO), lipoprotein-associated phospholipase A2 (Lp-PLA2), and oxidized low-density lipoprotein (OxLDL) were assessed using commercially available assays. Patients with FFR > 0.8 had higher sPLA2 activity, sPLA2 IIA, and OxLDL levels than patients with FFR ≤ 0.8 (21.25 [16.03-27.28] vs 25.85 [20.58-34.63] U/mL, p < 0.001, 2.0 [1.5-3.4] vs 2.6 [2.0-3.4] ng/mL, p < 0.01; and 53.0 [36.0-71.0] vs 64.5 [50-89.25], p < 0.001 respectively). Patients with FFR > 0.80 had similar Lp-PLA2 and MPO levels versus those with FFR ≤ 0.8. sPLA2 activity, sPLA2 IIA significantly increased area under the curve over baseline characteristics to predict FFR ≤ 0.8 (0.67 to 0.77 (95 % confidence interval [CI]: 0.69-0.85) p < 0.01 and 0.67 to 0.77 (95 % CI: 0.69-0.84) p < 0.01, respectively). Serum sPLA2 activity as well as sPLA2-IIA level is related to functional characteristics of coronary stenoses in patients with stable coronary artery disease.

Extent of coronary artery disease and outcomes after ticagrelor administration in patients with an acute coronary syndrome: Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial.

BACKGROUND Extensive coronary artery disease (CAD) is associated with higher risk. In this substudy of the PLATO trial, we examined the effects of randomized treatment on outcome events and safety in relation to the extent of CAD. METHODS Patients were classified according to presence of extensive CAD (defined as 3-vessel disease, left main disease, or prior coronary artery bypass graft surgery). The trial's primary and secondary end points were compared using Cox proportional hazards regression. RESULTS Among 15,388 study patients for whom the extent of CAD was known, 4,646 (30%) had extensive CAD. Patients with extensive CAD had more high-risk characteristics and experienced more clinical events during follow-up. They were less likely to undergo percutaneous coronary intervention (58% vs 79%, P < .001) but more likely to undergo coronary artery bypass graft surgery (16% vs 2%, P < .001). Ticagrelor, compared with clopidogrel, reduced the composite of cardiovascular death, myocardial infarction, and stroke in patients with extensive CAD (14.9% vs 17.6%, hazard ratio [HR] 0.85 [0.73-0.98]) similar to its reduction in those without extensive CAD (6.8% vs 8.0%, HR 0.85 [0.74-0.98], Pinteraction = .99). Major bleeding was similar with ticagrelor vs clopidogrel among patients with (25.7% vs 25.5%, HR 1.02 [0.90-1.15]) and without (7.3% vs 6.4%, HR 1.14 [0.98-1.33], Pinteraction = .24) extensive CAD. CONCLUSIONS Patients with extensive CAD have higher rates of recurrent cardiovascular events and bleeding. Ticagrelor reduced ischemic events to a similar extent both in patients with and without extensive CAD, with bleeding rates similar to clopidogrel.

An analysis of IN.PACT DEEP randomized trial on the limitations of the societal guidelines-recommended hemodynamic parameters to diagnose critical limb ischemia.

OBJECTIVE Recent small single-center data indicate that the current hemodynamic parameters used to diagnose critical limb ischemia are insensitive. We investigated the validity of the societal guidelines-recommended hemodynamic parameters against core laboratory-adjudicated angiographic data from the multicenter IN.PACT DEEP (RandomIzed AmPhirion DEEP DEB vs StAndard PTA for the treatment of below the knee Critical limb ischemia) Trial. METHODS Of the 358 patients in the IN.PACT DEEP Trial to assess drug-eluting balloon vs standard balloon angioplasty for infrapopliteal disease, 237 had isolated infrapopliteal disease with an available ankle-brachial index (ABI), and only 40 of the latter had available toe pressure measurements. The associations between ABI, ankle pressure, and toe pressure with tibial runoff, Rutherford category, and plantar arch were examined according to the cutoff points recommended by the societal guidelines. Abnormal tibial runoff was defined as severely stenotic (≥70%) or occluded and scored as one-, two-, or three-vessel disease. A stenotic or occluded plantar arch was considered abnormal. RESULTS Only 14 of 237 patients (6%) had an ABI <0.4. Abnormal ankle pressure, defined as <50 mm Hg if Rutherford category 4 and <70 mm Hg if Rutherford category 5 or 6, was found only in 37 patients (16%). Abnormal toe pressure, defined as <30 mm Hg if Rutherford category 4 and <50 mm Hg if Rutherford category 5 or 6, was found in 24 of 40 patients (60%) with available measurements. Importantly, 29% of these 24 patients had an ABI within normal reference ranges. A univariate multinomial logistic regression found no association between the above hemodynamic parameters and the number of diseased infrapopliteal vessels. However, there was a significant paradoxic association where patients with Rutherford category 6 had higher ABI and ankle pressure than those with Rutherford category 5. Similarly, there was no association between ABI and pedal arch patency. CONCLUSIONS The current recommended hemodynamic parameters fail to identify a significant portion of patients with lower extremity ulcers and angiographically proven severe disease. Toe pressure has better sensitivity and should be considered in all patients with critical limb ischemia.

Granulomatose com poliangeíte

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Ocular and systemic markers for vascular function in those at risk of type 2 diabetes mellitus and cardiovascular disease

The devastating impact of Type 2 Diabetes Mellitus (T2DM) -related morbidity and mortality on global healthcare is escalating with higher prevalences of obesity, poor diet, and sedentary lifestyles. Therefore, the clinical need for early diagnosis and prevention in groups of high-risk individuals is necessary. The purpose of this thesis was to investigate the use of surrogate markers, namely retinal vascular function, to determine future vascular endothelial dysfunction, atherosclerosis, large vessel disease and cardiovascular risk in certain groups. This namely covered normoglycaemic and normotensive South Asians (SAs), those with Impaired-Glucose Tolerance (IGT) and individuals with a familial history (FH) of T2DM. Additionally the effect of overweight and obesity was studied. The techniques and modified protocols adopted for this thesis involved the investigation of endothelial function by means of vascular reactivity at the ocular and systemic level. Furthermore, the relationships between retinal and systemic function with circulating markers for endothelial cell function and cardiovascular risk markers were explored. The principal studies and findings of the research were: Vascular Function in Normoglycaemic Individuals with and without a FH of T2DM WE FH individuals exhibited higher levels of total cholesterol levels that correlated well with the retinal arterial dilation amplitude to flicker light stimulus. However this did not extend to noticeable differences in markers for endothelial cell damage and impaired retinal and systemic function. Vascular Function in Normoglycaemic South-Asians vs. White-Europeans without a FH and Vascular Disturbances Compared to healthy WEs (normo -glycaemic and -tensive), SA participants exhibited levels of dyslipidaemia and a state of oxidative stress that extended to impaired vascular function as detected by reduced brachial artery flow-mediated dilation, slower retinal arterial vessel dilation reaction times (Appendix 3) and steeper constriction profiles. Furthermore, gender sub-group analysis presented in a sub-chapter shows that SA males demonstrated 24-hour systemic blood pressure (BP) and heart rate variability (HRV) abnormalities and heightened cardiovascular disease (CVD) risk. Vascular Function in Individuals Newly Diagnosed with IGT as compared to Normoglycaemic Healthy Controls Newly-diagnosed WE and SA IGT patients showed a greater risk for CVD and T2DM progression by means of 24-hour BP abnormalities, dyslipidaemia, increased carotid artery intimal-media thickness (c-IMT), Framingham scores and cholesterol ratios. Additionally, pre-clinical markers for oxidative stress and endothelial dysfunction, as evident by significantly lower levels of plasma glutathione and increased levels of von-Willebrand factor in IGT individuals, extended to impaired vascular systemic and retinal function compared to normal controls. This originally shows retinal, systemic and biochemical disturbances in newly-diagnosed IGT not previously reported before. Vascular Function in Normal, Overweight and Obese Individuals of SA and WE Ethnicity In addition to the intended study chapters, the thesis also investigated the influence of obesity and overweight on vascular function. Most importantly, it was found for the first time that compared to lean individuals it was overweight and not obese individuals that exhibited signs of vascular systemic and ocular dysfunction that was evident alongside markers of atherosclerosis, CVD risk and endothelial damage.

Atypical diagnosis by endoscopic capsule: Whipple's disease

Whipple's disease is a chronic systemic infection produced by the actinomycete Tropheryma whipplei. Endoscopic tests are key in the diagnosis as they allow biopsy and histopathological examination for definitive diagnosis of this entity. We present a case of Whipple's disease where capsule endoscopy, uncommon for the diagnosis of this condition, was essential for it and its performance before and after antibiotic treatment allows to describe the macroscopic evolution of the findings in the small bowel. This case illustrates the usefulness of capsule endoscopy to allow complete examination of the small bowel disease in which up to 30% of patients may present with normal endoscopy.

Caracterización y prevalencia del compromiso ocular en pacientes con enfermedad autoinmune y autoinflamatoria en un centro de referencia reumatológica en Colombia entre los años 2000 a 2015

RESUMEN Objetivo: Estimar la prevalencia de las diferentes enfermedades oftalmológicas que aparecen en el contexto de una enfermedad autoinmune (EAI) en pacientes de un centro de referencia reumatológica en Colombia, según características clínicas y sociodemográficas durante un período de 15 años, comprendido entre los años 2000 a 2015. Métodos: Se realizó un estudio descriptivo, observacional de prevalencia. El tipo de muestreo fue aleatorio estratificado con asignación proporcional en el programa Epidat 3.4. Los datos se analizaron en el programa SPSS v22.0 y se realizó análisis univariado de las variables categóricas, para las variables cuantitativas se realizaron medidas de tendencia central. Resultados: De 1640 historias clínicas revisadas, se encontraron 634 pacientes (38,65%) con compromiso ocular. Si excluimos los pacientes con SS, que por definición presentan ojo seco, 222 pacientes (13,53%) presentaron compromiso oftalmológico. Del total de pacientes, el 83,3% fueron mujeres. La AR fue la enfermedad autoinmune con mayor compromiso oftalmológico con 138 pacientes (62,2%), y en último lugar la sarcoidosis con 1 solo paciente afectado. La QCS fue la manifestación más común en todos los grupos diagnósticos de EAI, con 146 pacientes (63,5%). De 414 pacientes con Síndrome de Sjögren (SS) y QCS 8 presentaron compromiso ocular adicional, siendo la uveítis la segunda patología ocular asociada en pacientes con SS y la primera causa en las espondiloartropatias (71,4 %). Los pacientes con catarata (4,1%) presentaron la mayor prevalencia de uso de corticoide (88.8%). De 222 pacientes, 28 (12,6%) presentaron uveítis. Del total de pacientes, 16 (7,2%) presentaron maculopatía por antimalaráricos y 6 (18,75%) de los pacientes con LES. Los ANAS se presentaron en el 100% los pacientes con trastorno vascular de la retina. Los pacientes con epiescleritis presentaron la mayor proporción de positivización de anticuerpos anti-DNA. La EAI que más presentó epiescleritis fue LES con 4 pacientes (12,5%) El 22% de paciente con anticuerpos anti-RNP presentaron escleritis y 32,1% de los pacientes con uveítis presentaron HLA-B27 positivo. Las manifestaciones oftalmológicas precedieron a las sistémicas entre un 11,1% y un 33,3% de los pacientes. Conclusión: Las enfermedades oculares se presentan con frecuencia en los pacientes colombianos con EAI (38.65%), siendo la AR la enfermedad con mayor compromiso ocular (62,2%) y la QCS la enfermedad ocular con mayor prevalencia en todas las EAI (63,5%). La uveítis se presentó en 28 pacientes (12,6%). Las manifestaciones oftalmológicas pueden preceder a las sistémicas. El examen oftalmológico debe ser incluido en los pacientes con EAI, por ser la enfermedad ocular una comorbilidad frecuente. Adicionalmente, los efectos oftalmológicos de las medicaciones sistémicas utilizadas en EAI deben ser estrechamente monitorizados, durante el curso del tratamiento.

Volumetric Capnography For The Evaluation Of Chronic Airways Diseases.

Obstructive lung diseases of different etiologies present with progressive peripheral airway involvement. The peripheral airways, known as the silent lung zone, are not adequately evaluated with conventional function tests. The principle of gas washout has been used to detect pulmonary ventilation inhomogeneity and to estimate the location of the underlying disease process. Volumetric capnography (VC) analyzes the pattern of CO2 elimination as a function of expired volume. To measure normalized phase 3 slopes with VC in patients with non-cystic fibrosis bronchiectasis (NCB) and in bronchitic patients with chronic obstructive pulmonary disease (COPD) in order to compare the slopes obtained for the groups. NCB and severe COPD were enrolled sequentially from an outpatient clinic (Hospital of the State University of Campinas). A control group was established for the NCB group, paired by sex and age. All subjects performed spirometry, VC, and the 6-Minute Walk Test (6MWT). Two comparisons were made: NCB group versus its control group, and NCB group versus COPD group. The project was approved by the ethical committee of the institution. Statistical tests used were Wilcoxon or Student's t-test; P<0.05 was considered to be a statistically significant difference. Concerning the NCB group (N=20) versus the control group (N=20), significant differences were found in body mass index and in several functional variables (spirometric, VC, 6MWT) with worse results observed in the NCB group. In the comparison between the COPD group (N=20) versus the NCB group, although patients with COPD had worse spirometric and 6MWT values, the capnographic variables mean phase 2 slope (Slp2), mean phase 3 slope normalized by the mean expiratory volume, or mean phase 3 slope normalized by the end-tidal CO2 concentration were similar. These findings may indicate that the gas elimination curves are not sensitive enough to monitor the severity of structural abnormalities. The role of normalized phase 3 slope may be worth exploring as a more sensitive index of small airway disease, even though it may not be equally sensitive in discriminating the severity of the alterations.