Systems biology and artificial intelligence analysis highlights the pleiotropic effect of IVIg therapy in autoimmune diseases with a predominant role on B cells and complement system.

Intravenous immunoglobulin (IVIg) is used as treatment for several autoimmune and inflammatory conditions, but its specific mechanisms are not fully understood. Herein, we aimed to evaluate, using systems biology and artificial intelligence techniques, the differences in the pathophysiological pathways of autoimmune and inflammatory conditions that show diverse responses to IVIg treatment. We also intended to determine the targets of IVIg involved in the best treatment response of the evaluated diseases. Our selection and classification of diseases was based on a previously published systematic review, and we performed the disease characterization through manual curation of the literature. Furthermore, we undertook the mechanistic evaluation with artificial neural networks and pathway enrichment analyses. A set of 26 diseases was selected, classified, and compared. Our results indicated that diseases clearly benefiting from IVIg treatment were mainly characterized by deregulated processes in B cells and the complement system. Indeed, our results show that proteins related to B-cell and complement system pathways, which are targeted by IVIg, are involved in the clinical response. In addition, targets related to other immune processes may also play an important role in the IVIg response, supporting its wide range of actions through several mechanisms. Although B-cell responses and complement system have a key role in diseases benefiting from IVIg, protein targets involved in such processes are not necessarily the same in those diseases. Therefore, IVIg appeared to have a pleiotropic effect that may involve the collaborative participation of several proteins. This broad spectrum of targets and 'non-specificity' of IVIg could be key to its efficacy in very different diseases.

Severity scores should incorporate limitations on life support for predicting mortality / Las puntuaciones de intensidad deberían incorporar las limitaciones del soporte vital para predecir la mortalidad

No disponible

High red blood cell distribution width as a marker of hospital mortality after ICU discharge: a cohort study.

BACKGROUND: High red blood cell distribution width (RDW) is associated with worse outcome in diverse scenarios, including in critical illness. The Sabadell score (SS) predicts in-hospital survival after ICU discharge. We aimed to determine RDW's association with survival after ICU discharge and whether RDW can improve the accuracy of the SS. DESIGN: Retrospective cohort study. Setting: general ICU at a university hospital. PATIENTS: We included all patients discharged to wards from January 2010 to October 2016. METHODS: We analyzed associations between RDW and variables recorded on admission (age, comorbidities, severity score), during the ICU stay (treatments, complications, length of stay (LOS)), and at ICU discharge (SS). The primary outcome was hospital mortality. Statistical analysis included multivariable logistic regression and receiver operating characteristic curve (ROC) analyses. RESULTS: We discharged 3366 patients to wards; median ward LOS was 7 [4-13] days; ward mortality was 5.2%. Mean RDW at ICU discharge was 15.4 ± 2.5%. Ward mortality was higher at each quartile of RDW (0.7%, 2.9%, 7.5%, 10.3%; area under ROC 0.81). A logistic regression model with Sabadell score obtained an excellent accuracy for ward mortality (area under ROC 0.863), and the addition of RDW slightly improved accuracy (AUROC 0.890, p < 0.05). Recursive partitioning demonstrated higher mortality in patients with high RDW at each SS level (1.6% vs. 0.3% in SS0, 9.7% vs. 1.1% in SS1, 21.9% vs. 9.7% in SS2), but not in SS3. CONCLUSION: High RDW is a marker of severity at ICU discharge and improves the accuracy of Sabadell score in predicting ward mortality except in the more extreme SS3.

Addition of hyaluronic acid improves tolerance to 7% hypertonic saline solution in bronchiectasis patients.

BACKGROUND: The excessive retention of sputum in the airways, leading to pulmonary infections, is a common consequence of bronchiectasis. Although inhalation of 7% hypertonic saline (HS) has proven an effective method to help remove the mucus, many patients are intolerant of this treatment. The addition of 0.1% hyaluronic acid to HS (HS+HA) could increase tolerance to HS in these patients. The main objective of this study was to evaluate the tolerability of HS+HA in bronchiectasis patients who are intolerant to HS. METHODS: This prospective, observational, open-label study analysed the outcomes of two groups of bronchiectasis patients previously scheduled to start HS therapy. Patients were assessed for tolerance to HS by a questionnaire, spirometry and clinical evaluation. Patients who were intolerant were evaluated for tolerance to HS+HA approximately one week later. All patients were evaluated for their tolerance to HS or HS+HA 4 weeks after the start of their treatment. Patients were also assessed with quality-of-life and adherence questionnaires, and all adverse events were registered. RESULTS: A total of 137 bronchiectasis patients were enrolled in the study (age = 63.0 ± 14.7 years; 63.5% women). Of these, 92 patients (67.1%) were tolerant and 45 patients (32.9%) were intolerant to HS. Of the 45 patients intolerant to HS, 31 patients (68.9%) were tolerant and 14 patients (31.1%) intolerant to HS+HA. Of these 31 tolerant patients, 26 (83.9%) could complete the 4-week treatment with HS+HA. CONCLUSIONS: Two-thirds of bronchiectasis patients that presented intolerance to inhaled HS alone are tolerant to inhaled HS+HA, suggesting that HA improves tolerance to HS therapy.

Limitation of life support techniques at admission to the intensive care unit: a multicenter prospective cohort study.

PURPOSE: To determine the frequency of limitations on life support techniques (LLSTs) on admission to intensive care units (ICU), factors associated, and 30-day survival in patients with LLST on ICU admission. METHODS: This prospective observational study included all patients admitted to 39 ICUs in a 45-day period in 2011. We recorded hospitals' characteristics (availability of intermediate care units, usual availability of ICU beds, and financial model) and patients' characteristics (demographics, reason for admission, functional status, risk of death, and LLST on ICU admission (withholding/withdrawing; specific techniques affected)). The primary outcome was 30-day survival for patients with LLST on ICU admission. Statistical analysis included multilevel logistic regression models. RESULTS: We recruited 3042 patients (age 62.5 ± 16.1 years). Most ICUs (94.8%) admitted patients with LLST, but only 238 (7.8% [95% CI 7.0-8.8]) patients had LLST on ICU admission; this group had higher ICU mortality (44.5 vs. 9.4% in patients without LLST; p < 0.001). Multilevel logistic regression showed a contextual effect of the hospital in LLST on ICU admission (median OR = 2.30 [95% CI 1.59-2.96]) and identified the following patient-related variables as independent factors associated with LLST on ICU admission: age, reason for admission, risk of death, and functional status. In patients with LLST on ICU admission, 30-day survival was 38% (95% CI 31.7-44.5). Factors associated with survival were age, reason for admission, risk of death, and number of reasons for LLST on ICU admission. CONCLUSIONS: The frequency of ICU admission with LLST is low but probably increasing; nearly one third of these patients survive for ≥ 30 days.

Long-term clinical follow-up of patients undergoing percutaneous alcohol septal reduction for symptomatic obstructive hypertrophic cardiomyopathy.

BACKGROUND: Alcohol septal ablation (ASA) is an alternative treatment for symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients refractory to pharmacological therapy. We sought to evaluate the immediate and long-term incidence of death and changes in life quality in a consecutive cohort submitted to ASA. METHODS AND RESULTS: Between October 1998 and December 2013, a total of 56 patients (mean age 53.2 ± 15.5) with symptomatic refractory HOCM were treated with ASA and followed during 15 years (mean 8 ± 4 years). There were 7 (12.5%) deaths, 2 (3.6%) being of cardiac cause. The Kaplan-Meier survival probability estimate was 96.4% at 1 year, 87.7 at 5 years and 81.0% at 12 years post-ASA. Significant improvement was observed in life quality assessed by DASI index and NYHA functional class as well as in the left ventricle outflow tract (LVOT) gradient reduction (from 92.8 ± 3.3 mm Hg to 9.37 ± 6.7 mm Hg, P < 0.001) and septum thickness (from 23.9 ± 0.6 mm to 12.9 ± 1.0 mm, P < 0.001). Only one patient (1.7%) required permanent pacemaker immediately after ASA. During follow-up, one patient had a repeated ASA, three patients underwent myectomy and other four required ICD/pacemaker. In the multivariate model only post-ASA LVOT residual gradient and left ventricle mass were associated with worse prognosis. CONCLUSIONS: In this long-term clinical follow-up without losses, ASA was effective in improving quality of life and NYHA functional class, with relatively low mortality and very low need for immediate permanent pacemaker implantation. © 2016 Wiley Periodicals, Inc.

Long-term clinical follow-up of patients undergoing percutaneous alcohol septal reduction for symptomatic obstructive hypertrophic cardiomyopathy

BACKGROUND: Alcohol septal ablation (ASA) is an alternative treatment for symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients refractory to pharmacological therapy. We sought to evaluate the immediate and long-term incidence of death and changes in life quality in a consecutive cohort submitted to ASA. METHODS AND RESULTS: Between October 1998 and December 2013, a total of 56 patients (mean age 53.2 ± 15.5) with symptomatic refractory HOCM were treated with ASA and followed during 15 years (mean 8 ± 4 years). There were 7 (12.5%) deaths, 2 (3.6%) being of cardiac cause. The Kaplan-Meier survival probability estimate was 96.4% at 1 year, 87.7 at 5 years and 81.0% at 12 years post-ASA. Significant improvement was observed in life quality assessed by DASI index and NYHA functional class as well as in the left ventricle outflow tract (LVOT) gradient reduction (from 92.8 ± 3.3 mm Hg to 9.37 ± 6.7 mm Hg, P < 0.001) and septum thickness (from 23.9 ± 0.6 mm to 12.9 ± 1.0 mm, P < 0.001). Only one patient (1.7%) required permanent pacemaker immediately after ASA. During follow-up, one patient had a repeated ASA...

Pacientes com cardiomiopatia hipertrófica obstrutiva tratados com redução septal percutânea. Análise da evolução tardia / Patients with hypertrophic obstructive cardiomyopathy treated with percutaneous septal reduction. Analysis of long-term evolution

O tratamento alternativo de Redução septal percutânea (RSP) em pacientes com cardiomiopatia hipertrófica obstrutiva é relativamente novo e há poucos trabalhos publicados sobre a evolução tardia...

Randomized comparison of distal and proximal cerebral protection during carotid artery stenting.

OBJECTIVES: This study sought to randomly compare cerebral protection with ANGIOGUARD (Cordis Corporation, Bridgewater, New Jersey) with Mo.Ma (Invatec/Medtronic Vascular Inc, Santa Rosa, California) during carotid artery stenting (CAS), using diffusion-weighted magnetic resonance imaging (DW-MRI) to detect new ischemic cerebral lesions. The number, size, and location of lesions were analyzed. BACKGROUND: The choice of the type of cerebral protection during CAS is controversial. METHODS: From July 2008 to July 2011, 60 patients undergoing CAS were randomized to ANGIOGUARD or Mo.Ma, distributed by chance, 30 patients for each group. All patients underwent DW-MRI before and after CAS. An independent neuroradiologist blinded to the cerebral protection used analyzed the images. Univariate and multivariate logistic models were fitted to analyze new ischemic lesions. Alternatively, a propensity score approach was used to reduce the bias due to differences between the groups. For the number of lesions, we used Poisson regression models. RESULTS: New ischemic lesions seen on DW-MRI were present in 63.3% of the ANGIOGUARD group versus 66.7% of the Mo.Ma cohort (p = 0.787). The number of ischemic cerebral lesions per patient, when present, was significantly lower in the Mo.Ma group (a median of 6 lesions per patient vs. a median of 10 in the ANGIOGUARD, p < 0.001). Most lesions were small (<0.5 mm) and localized in the ipsilateral territory. One patient in the ANGIOGUARD group had a minor stroke during CAS (1.66%). CONCLUSIONS: New ischemic lesions seen on DW-MRI were present in both groups in >60%, but the number of lesions per patient was greater in the ANGIOGUARD group. No death or disabling stroke occurred during at least 1 year of follow-up in both cohorts.

Value of electro-vectorcardiogram in hypertrophic cardiomyopathy.

The electrocardiogram is an important tool for the initial diagnostic suspicion of hypertrophic cardiomyopathy in any of its forms, both in symptomatic and in asymptomatic patients because it is altered in more than 90 percent of the cases. Electrocardiographic anomalies are more common in patients carriers of manifest hypertrophic cardiomyopathy and the electrocardiogram alterations are earlier and more sensitive than the increase in left ventricular wall thickness detected by the echocardiogram. Nevertheless, despite being the leading cause of sudden death among young competitive athletes there is no consensus over the need to include the method in the pre-participation screening. In apical hypertrophic cardiomyopathy the electrocardiographic hallmarks are the giant negative T waves in anterior precordial leads. In the vectorcardiogram, the QRS loop is located predominantly in the left anterior quadrant and T loop in the opposite right posterior quadrant, which justifies the deeply negative T waves recorded. The method allows estimating the left ventricular mass because it relates to the maximal spatial vector voltage of the left ventricle in the QRS loop. The recording on electrocardiogram or Holter monitoring of nonsustained monomorphic ventricular tachycardia in patients with syncope, recurrent syncope in young patient, hypotension induced by strain, bradyarrhythmia, or concealed conduction are markers of poor prognosis. The presence of rare sustained ventricular tachycardia is observed in mid-septal obstructive HCM with apical aneurysm. The presence of complete right bundle branch block pattern is frequent after the percutaneous treatment and complete left bundle branch block is the rule after myectomy.

Proteção cerebral em pacientes idosos durante implante de stent carotídeo / Cerebral protection in elderly patients during carotid stenting

INTRODUÇÃO: O tipo de proteção cerebral utilizado durante o implante de stent carotídeo é controverso em idosos. Nosso objetivo foi avaliar os resultados dos dispositivos de proteção embólica cerebral (PEC), proximal e distal, em pacientes > 70 anos de idade, por meio da ressonância magnética ponderada de difusão (RM-PD). MÉTODOS: Entre 2008 e 2011, 60 pacientes com indicação de stent carotídeo foram randomizados para PEC com Mo.Ma® ou Angioguard®, dos quais 26 tinham > 70 anos de idade. Os resultados da RM-PD realizada antes e 48 horas após o procedimento foram avaliados por neuro­logista independente e cego para o tipo de PEC utilizado. Foram analisados o número de novos focos isquêmicos, sua localização e o tamanho. RESULTADOS: Novos focos isquêmicos cerebrais foram encontrados em 8/12 (66,7%) pacientes do grupo Mo.Ma® e em 12/14 (85,7%) pacientes do grupo Angioguard® (P = 0,37). A maioria das lesões (> 90%) era ipsilateral à artéria tratada em ambos os grupos, e o tamanho das lesões foi < 0,5 cm na maioria dos casos. O número de lesões por paciente foi menor com o dispositivo Mo.Ma® (mediana [variação]: 3 [1 a 8] lesões vs. 15 [2 a 76] lesões; P < 0,001). Todos os pacientes que tiveram mais de 40 lesões pertenciam ao grupo Angioguard®. CONCLUSÕES: Mesmo utilizando PEC (proximal ou distal), novas lesões isquêmicas foram observadas em ambos os grupos em pacientes idosos. Proporcionalmente maior número de pacientes com Angioguard® teve novos focos isquêmicos se comparados aos pacientes do grupo Mo.Ma®. O dispositivo de PEC Mo.Ma® parece diminuir o número de lesões por paciente.

BACKGROUND: The type of cerebral protection used during carotid stenting in the elderly is controversial. Our objective was to evaluate the results of proximal and distal cerebral embolic protection devices (EPDs), in patients > 70 years through diffusion-weighted magnetic resonance imaging (DW-MRI). METHODS: Between 2008 and 2011, 60 patients with indication for carotid stenting were randomized to EPD with Mo.Ma® or Angioguard®, of which 26 patients were > 70 years of age. Results of DW-MRI performed before and 48 hours after the procedure were evaluated by an independent neurologist blinded to the type of EPD used. New ischemic lesions, their localization and size were analyzed. RESULTS: New cerebral ischemic lesions were found in 8/12 (66.7%) patients in the Mo.Ma® group and 12/14 (85.7%) patients in the Angioguard® group (P = 0.37). The vast majority of the lesions (> 90%) were ipsilateral to the treated artery in both groups and the size of the lesions was < 0.5 cm in most cases. The number of lesions per patient was lower with the Mo.Ma® device (median [variation]: 3 [1 to 8] lesions vs 15 [2 to 76] lesions; P < 0.001). All of the patients with more than 40 lesions were in the Angioguard® group. CONCLUSIONS: Despite the use of EPDs (proximal or distal), new ischemic lesions were observed in both groups in elderly patients. A proportionately larger number of patients with Angioguard® had new ischemic lesions when compared to those with Mo.Ma®. The Mo.Ma® device seems to decrease the number of lesions per patient.

Randomized comparison of distal and proximal cerebral protection during carotid artery stenting

Objectives This study sought to randomly compare cerebral protection with ANGIOGUARD (CordisCorporation, Bridgewater, New Jersey) with Mo.Ma (Invatec/Medtronic Vascular Inc, Santa Rosa,California) during carotid artery stenting (CAS), using diffusion-weighted magnetic resonance imaging(DW-MRI) to detect new ischemic cerebral lesions. The number, size, and location of lesions wereanalyzed.Background The choice of the type of cerebral protection during CAS is controversial.Methods From July 2008 to July 2011, 60 patients undergoing CAS were randomized toANGIOGUARD or Mo.Ma, distributed by chance, 30 patients for each group. All patients underwentDW-MRI before and after CAS. An independent neuroradiologist blinded to the cerebral protectionused analyzed the images. Univariate and multivariate logistic models were fitted to analyze newischemic lesions. Alternatively, a propensity score approach was used to reduce the bias due todifferences between the groups. For the number of lesions, we used Poisson regression models.Results New ischemic lesions seen on DW-MRI were present in 63.3% of the ANGIOGUARD groupversus 66.7% of the Mo.Ma cohort (p » 0.787). The number of ischemic cerebral lesions per patient,when present, was significantly lower in the Mo.Ma group (a median of 6 lesions per patient vs.a median of 10 in the ANGIOGUARD, p 60%, but thenumber of lesions per patient was greater in the ANGIOGUARD group. No death or disabling strokeoccurred during at least 1 year of follow-up in both cohorts.

Alcohol septal ablation after myomectomy failure solutions for unusual cases.

We report an eight-year-old child presented with classical features of hypertrophic obstructive cardiomyopathy and with New York Heart Association (NYHA) class III symptoms, eight months after myectomy and refractory to medical treatment. Cardiac transplantation was indicated due to the severity of symptoms. But the lymphocyte reaction test showed almost 100% reaction of antibodies, and the surgeons rejected the heart transplantation for fear of hyperacute rejection. Then an alcohol septal ablation (ASA) was proposed, which was successfully performed on August 17, 2005. The post-extrasystolic gradient was reduced from 160 to 60 mm Hg immediately and no other complications were seen. The child is being followed since then and echocardiography changes include a further reduction of septum thickness and gradient (P = 0.001), and important symptoms relieved after 3.5 years of follow up. ASA may be an option to be considered in children with critical hypertrophic obstructive cardiomyopathy in NYHA functional class III/IV, when other methods of treatment failed. © 2010 Wiley-Liss, Inc.

Dense chromatin plates in metaphase chromosomes.

In a previous work we observed multilayered plate-like structures surrounding partially denatured HeLa chromosomes at metaphase ionic conditions. This unexpected finding has led us to carry out an extensive investigation of these structures. Our results show that plates can also be found in metaphase chromosomes from chicken lymphocytes. We have used atomic force microscopy (AFM) to image and investigate the mechanical properties of plates in aqueous solution. Plates are thin (approximately 6.5 nm each layer) but compact and resistant to penetration by the AFM tip: their Young's modulus is approximately 0.2 GPa and the stress required for surface penetration is approximately 0.03 GPa in the presence of Mg(2+) (5-20 mM). Low-ionic strength conditions produce emanation of chromatin fibers from the edges of uncrosslinked plates. These observations and AFM results obtained applying high forces indicate that the chromatin filament is tightly tethered inside the plates. Images of metal-shadowed plates and cryo-electron microscopy images of frozen-hydrated plates suggest that nucleosomes are tilted with respect to the plate surface to allow an interdigitation between the successive layers and a thickness reduction compatible with the observed plate height. The similarities between denatured plates from chicken chromosomes and aggregates of purified chromatin from chicken erythrocytes suggest that chromatin has intrinsic structural properties leading to plate formation. Scanning electron micrographs and images obtained with the 200-kV transmission microscope show that plates are the dominant component of compact chromatids. We propose that metaphase chromosomes are formed by many stacked plates perpendicular to the chromatid axis.