[Case Report: MPO-ANCA Associated Vasculitis After Pfizer-BioNTech COVID-19 mRNA Vaccination].

We report a case of MPO-anti-neutrophil cytoplasmic antibody ANCA-associated vasculitis, with pulmonary-renal syndrome, after the mRNA booster third dose vaccine Pfizer BioNTech against COVID-19 in 71-year-old Caucasian man with no specific past medical history. A kidney biopsy diagnosed ANCA-associated pauci-immune crescentic glomerulonephritis. Renal function and constitutional symptoms have been partially improved with treatment with dialysis, intravenous rituximab and steroid pulse therapy. No disease following either infection or vaccination with fourth dose against COVID-19.

A Bayesian generative neural network framework for epidemic inference problems.

The reconstruction of missing information in epidemic spreading on contact networks can be essential in the prevention and containment strategies. The identification and warning of infectious but asymptomatic individuals (i.e., contact tracing), the well-known patient-zero problem, or the inference of the infectivity values in structured populations are examples of significant epidemic inference problems. As the number of possible epidemic cascades grows exponentially with the number of individuals involved and only an almost negligible subset of them is compatible with the observations (e.g., medical tests), epidemic inference in contact networks poses incredible computational challenges. We present a new generative neural networks framework that learns to generate the most probable infection cascades compatible with observations. The proposed method achieves better (in some cases, significantly better) or comparable results with existing methods in all problems considered both in synthetic and real contact networks. Given its generality, clear Bayesian and variational nature, the presented framework paves the way to solve fundamental inference epidemic problems with high precision in small and medium-sized real case scenarios such as the spread of infections in workplaces and hospitals.

Epidemic mitigation by statistical inference from contact tracing data.

Contact tracing is an essential tool to mitigate the impact of a pandemic, such as the COVID-19 pandemic. In order to achieve efficient and scalable contact tracing in real time, digital devices can play an important role. While a lot of attention has been paid to analyzing the privacy and ethical risks of the associated mobile applications, so far much less research has been devoted to optimizing their performance and assessing their impact on the mitigation of the epidemic. We develop Bayesian inference methods to estimate the risk that an individual is infected. This inference is based on the list of his recent contacts and their own risk levels, as well as personal information such as results of tests or presence of syndromes. We propose to use probabilistic risk estimation to optimize testing and quarantining strategies for the control of an epidemic. Our results show that in some range of epidemic spreading (typically when the manual tracing of all contacts of infected people becomes practically impossible but before the fraction of infected people reaches the scale where a lockdown becomes unavoidable), this inference of individuals at risk could be an efficient way to mitigate the epidemic. Our approaches translate into fully distributed algorithms that only require communication between individuals who have recently been in contact. Such communication may be encrypted and anonymized, and thus, it is compatible with privacy-preserving standards. We conclude that probabilistic risk estimation is capable of enhancing the performance of digital contact tracing and should be considered in the mobile applications.

Lipoprotein apheresis downregulates IL-1α, IL-6 and TNF-α mRNA expression in severe dyslipidaemia.

BACKGROUND AND AIMS: Dyslipidaemias are associated with cardiovascular mortality and morbidity, driven by unstable atherosclerotic plaques with inflammatory infiltrates. Levels of messenger RNA (mRNA) for pro-inflammatory cytokines have been positively correlated with atherosclerotic disease progression. Therapeutic lipoprotein apheresis (LA) reduces plasma lipid levels and reduces inflammation. We evaluated the effects of LA on expression of mRNA coding for key pro-inflammatory cytokines in patients with dyslipidaemia, homo-/hetero-zygous familial hypercholesterolaemia (HoFH, HeFH) or hyperlipoprotein(a)aemia [hyperLp(a)] and associated coronary artery disease (CAD). APPROACH: Ten patients (five males and five females, mean age 47 ± 9.2 years) were enrolled, all with HyperLp(a) or confirmed genetic diagnoses of dyslipidaemia, HoFH, or HeFH; all had associated CAD. mRNA determinations were via reverse transcriptase polymer chain reaction (RT-qPCR). RESULTS: LA was associated with downregulation of mRNA expression for IL-1α, IL-6 and TNF-α, starting after the first LA session. The observed reduction was progressively enhanced during the interval between the first and second LA sessions to achieve a maximum decrease by the end of the second session (IL-1α: -49%, p < 0.001; IL-6: -35%, p < 0.001; TNF-α: -56%, p < 0.001). CONCLUSIONS: LA suppresses the expression of IL-1α, IL-6 and TNF-α mRNA in patients with dyslipidaemias. This may contribute to the arterial anti-inflammatory effect of LA.

Monascus purpureus for statin and ezetimibe intolerant heterozygous familial hypercholesterolaemia patients: A clinical study.

BACKGROUND: Hypercholesterolaemia is a major risk factor for cardiovascular disease and requires effective therapy in affected patients. Statins, the mainstay of lipid-lowering therapy, can cause side effects, including myalgia, in some patients. Ezetimibe, is frequently used as an add-on therapy for statins, and is also used as a monotherapy in statin-intolerant patients, however elevations in liver transaminases can occur. We examined the lipid-lowering efficacy of the natural fungal product Monascus purpureus (MP), which contains the natural statin monacolin K. METHODS: Fifty-five patients with familial hypercholesterolaemia who had discontinued statins due to muscle symptoms. Patients were placed on a lipid-lowering diet cholesterol-lowering diet (1500-1800 kcal daily, 30% lipids, 19% proteins and 52% carbohydrates). MP was added to the diet at a dose of 300 mg (providing monacolin K 10 mg). Patients were followed for 12 months. Lipid profiles and adverse event data were collected in the normal course of patient care. RESULTS: After 6 months of treatment with MP and diet therapy, statistically significant changes in low-density lipoprotein cholesterol were evident (-17% for males, -16% for females; p < 0.005) Levels fell to -24% and -27% respectively at 12 months. No patients experienced elevated serum aminotransferases or C-reactive protein levels. CONCLUSIONS: MP is a viable option for lipid-lowering therapy in statin-intolerant patients with hypercholesterolaemia, with good efficacy and safety profiles.

Relationship between Sustained Reductions in Plasma Lipid and Lipoprotein Concentrations with Apheresis and Plasma Levels and mRNA Expression of PTX3 and Plasma Levels of hsCRP in Patients with HyperLp(a)lipoproteinemia.

The effect of lipoprotein apheresis (Direct Adsorption of Lipids, DALI) (LA) on plasma levels of pentraxin 3 (PTX3), an inflammatory marker that reflects coronary plaque vulnerability, and expression of PTX3 mRNA was evaluated in patients with hyperLp(a)lipoproteinemia and angiographically defined atherosclerosis/coronary artery disease. Eleven patients, aged 55 ± 9.3 years (mean ± SD), were enrolled in the study. PTX3 soluble protein levels in plasma were unchanged by 2 sessions of LA; however, a downregulation of mRNA expression for PTX3 was observed, starting with the first session of LA (p < 0.001). The observed reduction was progressively increased in the interval between the first and second LA sessions to achieve a maximum decrease by the end of the second session. A statistically significantly greater treatment-effect correlation was observed in patients undergoing weekly treatments, compared with those undergoing treatment every 15 days. A progressive reduction in plasma levels of C-reactive protein was also seen from the first session of LA, with a statistically significant linear correlation for treatment-effect in the change in plasma levels of this established inflammatory marker (R(2) = 0.99; p < 0.001). Our findings suggest that LA has anti-inflammatory and endothelium protective effects beyond its well-established efficacy in lowering apoB100-containing lipoproteins.

Decisões judiciais e orçamento: um olhar sobre a saúde pública / Judgments and budget: a look at the public health

O presente artigo tem por objetivo questionar o posicionamento do Supremo Tribunal Federal (STF), ao analisar os acórdãos que tratam do direito à saúde e orçamento público em 2011. Busca-se responder à seguinte questão: durante 2011, passados mais de 20 anos da promulgação da Constituição Federal de 1988 (que institucionalizou as regras orçamentárias em nosso país) e mais de 10 anos de vigência da Lei de Responsabilidade Fiscal, em que medida as decisões judiciais junto às prestações de serviços de saúde não observam as leis orçamentárias podendo, dessa forma, comprometer o orçamento em saúde e prejudicar a concretização da política de saúde universal planejada? Para a elaboração do artigo foram realizadas pesquisas bibliográfica e documental, com base na literatura referente ao direito fundamental social à saúde, no marco do Estado Democrático de Direito, bem como ao fenômeno da judicialização da saúde e da institucionalização das finanças públicas no país, a partir da Constituição de 1988. Também foram analisados acórdãos do STF do ano de 2011, identificados por meio de pesquisa jurisprudencial, no site do STF, com a utilização das palavras-chave “direito”; “saúde”; “orçamento”; e “art.196”. Este artigo chama a atenção para a forma como o STF vem decidindo sobre essas questões, além de apontar para a necessidade de mais discussão e de realização de um estudo de maior amplitude no campo do direito à saúde e orçamento público.

This article aims to discuss the position of the Brazilian Supreme Court, by analyzing the judgments related to the right to health and public budget during 2011. It seeks to answer the following question: during the year 2011, after more than 20 years since the promulgation of the Brazilian 1988 Constitution (which established the budget rules in our country) and more than 10 years of the Brazilian Fiscal Responsibility Act, the extent to which judicial decisions with the provision of health services do not meet the budget laws and may thus jeopardize the health budget and the achievement of the planned universal health policy? To elaborate this paper was developed bibliographical and documental research based on the literature related to the fundamental social right to health, in the framework of the Rule of Law, as well as the literature related to the phenomenon of the judicialization of health and institutionalization of public finances in Brazil, after the 1988 Constitution. Supreme Court’s decisions during the year of 2011 were also surveyed at the court’s website, using the following keywords: “right”, “health”, “budget” and “art. 196”. This article highlights theway Supreme Court has decided these issues and points to the need of more discussion and investigation about the right to health and public budget.

Os impasses entre a judicialização da saúde e o processo orçamentário sob a responsabilidade fiscal: uma análise dos fundamentos decisórios do Supremo Tribunal Federal / The impasses between judicialization of healthy and budgetary process under fiscal responsibility an analysis on decision fundaments of Ultimate Federal Tribunal

Introdução - O Direito à saúde garantido constitucionalmente muitas vezes só pode ser efetivado por meio da intervenção do Poder Judiciário. No entanto, esta intervenção também chamada de judicialização, acaba por causar consequências no campo das finanças públicas quando não observadas as regras e o planejamento orçamentário. Objetivo - O presente trabalho tem por objetivo questionar o posicionamento do Supremo Tribunal Federal (STF) nos anos de 2000 a 2011, ao analisar os acórdãos que se referem ao direito à saúde. Busca-se responder a seguinte questão: Passados mais de vinte anos desde a promulgação da Constituição Federal de 1988 (que institucionalizou as regras orçamentárias em nosso país), e mais de dez anos de vigência da Lei de Responsabilidade Fiscal (Lei nº 101/2000 que trata da responsabilidade na gestão fiscal), em que medida as decisões judiciais junto às prestações de serviços de saúde observam as leis orçamentárias podendo, eventualmente, comprometer o orçamento em saúde e prejudicar a concretização da política de saúde universal planejada? Métodos - O trabalho foi realizado mediante pesquisa bibliográfica e documental, bem como por meio do levantamento e análise de acórdãos do STF, nos anos de 2000 a 2011. A escolha do ano de 2011 se deu pelo fato de já se ter passado mais de vinte anos desde a promulgação do texto Constitucional de 1988, e mais de 10 anos de vigência da Lei de Responsabilidade Fiscal. O levantamento dos acórdãos ocorreu por meio de pesquisa jurisprudencial, no sítio eletrônico do STF, com a utilização de jogos de combinação de palavras chave, quais sejam: saúde e responsabilidade e 196; direito e saúde e orçamento e responsabilidade; orçamento e saúde e 196; 196 e orçamento; 196 e saúde; medicamento e orçamento e 196; medicamento e saúde; direito e saúde e medicamento e orçamento; direito e saúde e judicialização; judicialização e medicamento; judicialização e 196; judicialização e orçamento; direito e medicamento; orçamento e saúde; medicamento e orçamento; medicamento e 196, medicamento e fornecimento, afim de se obter o maior espectro possível de resultados, tendo como base para a pesquisa o item pesquisa de acórdãos. A pesquisa documental e bibliográfica teve como base a literatura referente ao direito fundamental social à saúde, no marco do Estado Democrático de Direito, bem como o fenômeno da judicialização da saúde e da institucionalização das finanças públicas no País, a partir da Constituição de 1988

Multiple lipid-lowering treatment in pediatric patients with hyperlipidemia.

256 pediatric patients with primary hyperlipidemia aged 14.2 ± 8.5 years (females: 155; males:101) seen in our lipid clinic were evaluated retrospectively to assess the effect of multiple lipid-lowering treatment (diet only, diet+glucomannan 1.000 mg/day (G), diet+ezetimibe (E) 10 mg/day and diet+atorvastatin (A) 10 mg/day). The patients were assigned to four groups according to their type of treatment: A-Diet (#82; age 12.7 ± 8 years; females 52, males:30); B-Diet+G (#78; age 13.3 ± 9 years; females 61, males 17); C-Diet+E 10 mg/day (#50; age 14.5 ± 7 years; females 31, males 19); D-Diet+A 10 mg/day (#46; age 16.4 ± 10 years; males 35, females 11). The follow-up visits were at 3, 6 and 9 months, respectively. The time period considered was of 9 months. The results obtained in the four groups after 9 months of treatment are given below: GROUP A: Total Cholesterol (TC) (-20%), LDL-Cholesterol (LDLC) (-26%), triglycerides (TG) (-25%), nonHDL-Cholesterol (nonHDLC) (-26%) levels, and TC/HDLC ratio (-21%) were statistically significant reduced (all: P < 0001). HDLC was not significantly increased (+2%). The body weight (BW) mean change in the group was statistically significant (-22%; P≤0.001). GROUP B: TC (-24%), LDLC (-32%), TG (-29%), nonHDLC (-32%) levels and TC/HDLC (-26%) were significantly decreased (all: P≤0.001). HDLC showed a -2.3% not significant decrease. The BW mean change was not statistically significant (-18%). GROUP C: TC (-36%), LDLC (-51%), nonHDLC (-45%) levels and TC/HDLC (-38%) were significantly decreased (all: P≤0.001). HDLC (+4%) was only slightly increased, and TG (-16%) decreased, but the changes were not statistically significant. The BW mean change was not statistically significant (-15%). GROUP D: TC (-47%), LDLC (-63%), TG (-23%) and nonHDLC (-58%) levels and TC/HDLC (-50%) showed a statistically significant reduction (all: P≤0001). HDLC concentration in plasma showed only a slight not significant reduction (-4%). The BW mean change was statistically significant (-20%; P≤0.001). Hyperlipidemia in children can be successfully treated without side effects. The most severe hyperlipidemia is, the most appropriate treatment (diet only,or diet+G, or diet+drugs) is to be given. The reduction of TC/HDLC ratio in childhood prevents future increase of cardiovascular risk in adulthood.

[New therapeutic prospects for renal transplant: extracorporeal photochemotherapy]. / Nuove prospettive terapeutiche per il trapianto di rene: la fotochemioterapia extracorporea.

Since 1960, different classes of immunosuppressive drugs have been used in the post-transplant follow-up. Each is assessed for its effectiveness in preventing rejection but also on the basis of the many side effects induced by prolonged treatment. To reduce these side effects, continuous development of knowledge and medical technology to create cutting-edge therapies in the field is necessary. One of these is extracorporeal photochemotherapy (ECP), an immunomodulatory therapy approved by the United States Food and Drug Administration in 1988 for the treatment of advanced forms of cutaneous T-cell lymphoma. EC P is a useful therapeutic tool for the development of immunomodulation supported by CD8+ clone-specific cytotoxic lymphocytes. The T cells targeted by EC P are modified by photoactivation and seem to develop marked immunogenicity with no suppression of the immune response. Recent studies suggest the possible utility of EC P in the treatment of glomerulonephritis and in countering rejection after transplantation of organs including the kidney.

Immunoadsorption apheresis and immunosuppressive drug therapy in the treatment of complicated HCV-related cryoglobulinemia.

The immunosuppressive drug therapy (IDT) is not always effective to avoid the development of complications in hepatitis C virus-related cryoglobulinemia (HCV-Cr). Removal of cryoglobulins by therapeutic plasmapheresis is currently accepted. In this randomized, parallel group study, 17 male and female patients aged 43-79 years, with complicated HCV-Cr, were submitted for 12 weeks (initial immunosuppressive therapy) to IDT (alpha-interferon, pegylated-interferon alpha-2a, cyclophosphamide, methylprednisolone, prednisone, cyclosporine, ribavirin, and melphalan). Then, they were randomly assigned to two parallel groups: A # 9 patients treated by immunoadsorption apheresis (Selesorb((R))) (IA) plus IDT, and B # 8 patients submitted to IDT only, for further 12 weeks. # 187 IA aphereses were performed. No adverse reactions or complications were observed. A Clinical Score (CS) was adapted from a pre-existing scoring model to evaluate signs and symptoms inherent to the underlying immunologic disorder. The CS was calculated at baseline (CS0), after the initial immunosuppressive therapy (CS1 = 12 weeks) when patients were treated only with IDT, and at the end of the study (24 weeks) in the group A (CSA; IA plus IDT) and B (CSB; IDT only). The score did not change significantly from CS0 to CS1. However, statistically significant differences were observed between CS1 and CSA (P < 0.001), and CSA versus CSB (P = 0.03), respectively. The changes observed were favorable to the patients assigned to the IA plus IDT group (A): in most case relief of symptoms and complications have been obtained.

Combined treatment with Dif1stat and diet reduce plasma lipid indicators of moderate hypercholesterolemia more effectively than diet alone: a randomized trial in parallel groups.

An open-labeled randomized trial with parallel groups was carried out to study the effects of Dif1stat (Monascus purpureus-Linear aliphatic alcohols-Niacin) in the treatment of primary moderate hypercholesterolemia. The trial lasted 8 months. The patients, males and females, were assigned to two groups: A (#130), treated with diet, and B (#110) submitted to diet + Dif1stat. After 4 months, group A did not show significant changes in Total cholesterol (TC), LDL-cholesterol (LDLC), HDL-cholesterol (HDLC) or non-HDL-cholesterol (non-HDLC). The same group, showed a reduction in TC (-22%), LDLC (-30%) and non-HDLC (-27%) after 8 months (P < or = 0.001). After 4 months, TC (-21.3%), LDLC (-29%), and non-HDLC (-26%) were significantly lowered in group B (P < or = 0.001). In group B, TC, LDLC and non-HDLC showed a further reduction after 8 months: -29.4, -38 and -37%, respectively (P < or = 0.001). Even triglycerides (TG) decreased significantly (-33%) (P < or = 0.001). After 8 months, group B showed a significant reduction of TG (-33%) (P < or = 0.001), when compared to group A. Some safety parameters were significantly reduced in both groups: AST and gamma-GT in group A after 4 and 8 months, as well as ALT, AST and gamma-GT in group B after 8 months (P < or = 0.001). Dif1stat, given with a suitable diet, was well tolerated in the long-term and induced an anti-atherogenic plasma lipid and lipoprotein profile, in patients with moderate hypercholesterolemia.

Therapeutic plasma exchange in patients with severe hypertriglyceridemia: a multicenter study.

Extremely high plasma triglyceride (TG) concentration is a recognized risk factor for acute pancreatitis (AP). In order to evaluate the therapeutic efficacy of plasma-exchange plasmapheresis in treating patients with severe hypertriglyceridemia (sHTG), 17 patients who had not responded to conventional medical therapy (fat-free diet plus pharmaceutical interventions) were referred for therapeutic plasma exchange (TPE) in a multicenter frame case series study. Two hundred seventeen TPE sessions were performed, and therapy is ongoing for five (30%) of the patients. After treatment, the mean plasma TG and total cholesterol concentrations were significantly reduced from 1929 and 510 mg/dL, to 762 and 227 mg/dL, respectively (P < or = 0.001 in both cases). In most cases, the interval between treatments was related to the clinical presentation and individual circumstances. The removal of TG-rich lipoproteins prevented relapses of AP. In this case series, TPE is confirmed as a safe and reliable method for treating patients with refractory sHTG when a severe complication, such as AP, is clinically demonstrated or can be actively prevented. Therefore, in cases where standard medical approaches fail to promote the clearance of TGs from plasma and a high risk of first or second hypertriglyceridemic pancreatitis persists, TPE provides a therapeutic option for preventing life-threatening sHTG.

Effects of low-dose atorvastatin and rosuvastatin on plasma lipid profiles: a long-term, randomized, open-label study in patients with primary hypercholesterolemia.

BACKGROUND AND OBJECTIVE: Despite the favorable effects of reduction of low-density lipoprotein-cholesterol (LDL-C) levels in decreasing the risk of coronary heart disease, many patients treated with lipid-lowering HMG-CoA reductase inhibitors (statins) do not achieve goal LDL-C levels. This may be due to high doses of statins prescribed that could potentially induce adverse effects and compromise patient safety and compliance with considerable expense in the long-term. We compared the actions of rosuvastatin and atorvastatin, administered at the low dosages of 10 and 20 mg/day, respectively, in reducing plasma LDL-C levels and their effects on other components of the atherogenic lipid profile in patients with primary hypercholesterolemia. METHODS: In this randomized, parallel group, open-label clinical study, 106 patients with LDL-C >200 mg/dL were treated with rosuvastatin 10 mg/day (group A; n = 52), or atorvastatin 20 mg/day (group B; n = 54) for 48 weeks. RESULTS: At 48 weeks, rosuvastatin 10 mg/day was associated with a significantly greater reduction in plasma LDL-C levels compared with atorvastatin 20 mg/day (-44.32% vs -30%; p < 0.005). Compared with atorvastatin, rosuvastatin also produced a greater reduction in plasma total cholesterol, triglycerides, and non-high-density lipoprotein-cholesterol (non-HDL-C) levels (p < 0.005). Plasma HDL-C levels were not affected significantly, independent of the drug used. CONCLUSION: In high-risk patients with primary hypercholesterolemia, rosuvastatin 10 mg/day was more efficacious than atorvastatin 20 mg/day in reducing plasma LDL-C levels, enabling goal LDL-C levels to be achieved and improving other lipid parameters. Both treatments were well tolerated over 48 weeks.