The interplay between antioxidants and the immune system. A promising field, still looking for answers

Editoriale su review inerente il ruolo del resveratrolo e degli antiossidanti nelle risposta immun

Association between proton-pump inhibitors (PPI) and metronomic capecitabine (MCAP) as salvage treatment for patients with advanced gastro-intestinal tumoursa. A randomized phase II study

Background: Several researches have shown that acidification of tumor microenvironment is the basis for tumor invasiveness, ability to metastasize S382 Abstracts and cytotoxic agents resistance; therefore proton pump inhibitors (PPI) could significantly increase the chemosensitivity. In our retrospective work we have investigated the role of capecitabine (mCAP) at metronomic dosage of 1500 mg/die as salvage chemotherapy in patients with metastatic colorectal cancer, showing a moderately activity and well tolerability. In this prospective study we evaluated safety and activity of mCAP in the advanced gastro-intestinal patients and the putative chemosensitizing activity of a specific PPI (Rabeprazole) in association to this therap

Criptococose cutânea disseminada em paciente com SIDA. Relato de caso

The authors study a patient carrying Aids, with exuberant dermatological manifestations of cryptococcosis. They stress the therapeutic effectiveness of short-term amphotericin B. The authors reviewed cases of cutaneous infection with Cryptococcus reported in the national and international literature, verifying that the frequency has increased with the AIDS epidemic. Also, they discuss about the differential diagnosis with some cases of dermatosis, particularly with the disseminated giant molluscum contagiosum. In relation to the therapy, they affirm that the choice of drug depends on the organ involved, as well as the immune state of the patient.Os autores estudam um paciente portador de SIDA, com manifestações dermatológicas exuberantes de criptococose. Destacam a eficácia terapêutica da anfotericina B, a curto prazo. Revisam os casos de criptococose cutânea relatados na literatura nacional e internacional, ressaltando o aumento de sua freqüência com a epidemia da SIDA. Também discutem o diagnóstico diferencial com várias dermatoses, particularmente com o molusco contagioso gigante disseminado. Em relação à terapêutica, afirmam que a escolha da droga depende do órgão comprometido, assim como do estado imunológico do paciente

Case for diagnosis

O termo úlcera de Marjolin é usado para designar a transformação maligna que se origina na pele cronicamente lesada. Trata-se de neoplasia mais agressiva do que aquelas não relacionadas com cicatriz e, frequentemente, é subdiagnosticada ou tratada de forma inadequada. Relatamos a ocorrência de carcinoma, do tipo espinocelular sobre cicatriz de queimadura, salientando a necessidade do diagnóstico e intervenção precoces visando um melhor prognósticoMarjolin's ulcer is a term used to describe a malignant transformation that originates in chronic skin lesions. These neoplasms may be more aggressive than those unassociated with healing processes and are frequently overlooked or inadequately treated. This case report describes the occurrence of a squamous cell carcinoma occurring at the site of a burn scar and emphasizes the need for early diagnosis and treatment in order to assure better prognosi

Combination therapy of high-dose rabeprazole plus metronomic capecitabine in advanced gastrointestinal cancer: a randomized phase II trial

Abstract: Background: In recent years, proton pump inhibitors (PPIs) have been investigated at high-dose tomodulate tumormicroenvironment acidification thus restoring chemotherapeutic sensitivity. This is the first trial to study activity and safety of repurposing high dose rabeprazole combined with metronomic capecitabine (mCAP). Methods: A phase II study in which patients with gastrointestinal cancer, refractory to standard treatments, who had a life expectancy >3 months, were blind randomized 1:1 to mCAP, 1500 mg/daily, continuously with or without rabeprazole 1.5 mg/kg bid, three days a week. The primary endpoint was 3-months progression-free survival (PFS). The secondary endpoints were clinical benefit (CB) and overall survival (OS). Safety and plasma concentrations of capecitabine and its metabolites (50-DFUR and 5-FU) were also evaluated. Results: Sixty-seven (median age 69 years; 63% male; 84% colorectal cancer, 76% ECOG-PS 1; 84% pretreated with two or more lines of chemotherapy) out of 90 patients screened for eligibility, were randomized to receive mCAP+rabeprazole (n = 32) vs. mCAP (n = 35). All patients were evaluable for response. No significant dierence between mCAP+rabeprazole vs. mCAP, in terms of 3-months PFS rate (HR = 1.43, 95%CI 0.53–3.85; p = 0.477), median PFS (HR = 1.22, 95%CI 0.75–2.00, p = 0.420), CB (RR = 0.85, 95%CI 0.29–2.44; p = 0.786) and median OS (HR = 0.89, 95%CI 0.54–1.48; p = 0.664) was observed. However, a 3-year OS rate of 10% and 12% was reported in the mCAP-rabeprazole and mCAP groups, respectively. Overall, no grade 3 or 4 toxicity occurred but grade 1 or 2 adverse event of any type were more frequently in the mCAP+rabeprazole group than in the mCAP (OR 2.83, 95%CI 1.03–7.79; p = 0.043). Finally, there was not statistically significant dierence in the plasma concentration of capecitabine and its metabolites between the two groups. Conclusions: Although the adjunct of high dose rabeprazole to mCAP was not shown to aect mCAP activity, as PPI are being investigated worldwide as drugs to be repositioned in cancer treatment and also considering the limited sample size as well as the favorable safety profile of the combination in the present study, further clinical investigations are desirable

Prevalence of right ventricular dysfunction and impact on all-cause death in hospitalized patients with COVID-19: a systematic review and meta-analysis

The Coronavirus Disease (COVID-19) pandemic imposed a high burden of morbidity and mortality. In COVID-19, direct lung parenchymal involvement and pulmonary microcirculation dysfunction may entail pulmonary hypertension (PH). PH and direct cardiac injury beget right ventricular dysfunction (RVD) occurrence, which has been frequently reported in COVID-19 patients; however, the prevalence of RVD and its impact on outcomes during COVID-19 are still unclear. This study aims to evaluate the prevalence of RVD and associated outcomes in patients with COVID-19, through a Systematic Review and Meta-Analysis. MEDLINE and EMBASE were systematically searched from inception to 15th July 2021. All studies reporting either the prevalence of RVD in COVID-19 patients or all-cause death according to RVD status were included. The pooled prevalence of RVD and Odds Ratio (OR) for all-cause death according to RVD status were computed and reported. Subgroup analysis and meta-regression were also performed. Among 29 studies (3813 patients) included, pooled prevalence of RVD was 20.4% (95% CI 17.1-24.3%; 95% PI 7.8-43.9%), with a high grade of heterogeneity. No significant differences were found across geographical locations, or according to the risk of bias. Severity of COVID-19 was associated with increased prevalence of RVD at meta-regression. The presence of RVD was found associated with an increased likelihood of all-cause death (OR 3.32, 95% CI 1.94-5.70). RVD was found in 1 out of 5 COVID-19 patients, and was associated with all-cause mortality. RVD may represent one crucial marker for prognostic stratification in COVID-19; further prospective and larger are needed to investigate specific management and therapeutic approach for these patients

Distinct platelet crosstalk with adaptive and innate immune cells after adenoviral and mRNA vaccination against SARS-CoV-2

Background: Genetic-based COVID-19 vaccines have proved highly effective in reducing the risk of hospitalization and death. As they were first distributed on a large-scale population, adenoviral-based vaccines were linked to a very rare thrombosis with thrombocytopenia syndrome and the interplay between platelets and vaccinations increasingly gained attention. Objective: To study the crosstalk between platelets and the vaccine-induced immune response. Methods: We prospectively enrolled young healthy volunteers who received the mRNA-based vaccine, BNT162b2 (n=15), or the adenovirus-based vaccine, AZD1222 (n=25) and studied their short-term platelet and immune response before and after vaccine injections. In a separate cohort, we retrospectively analysed the effect of aspirin on the antibody response 1 and 5 months after BNT162b2 vaccination. Results: Here we show that a faster antibody response to either vaccine is associated to the formation of platelet aggregates with marginal zone-like B-cells, a subset geared to bridge the temporal gap between innate and adaptive immunity. However, while the mRNA-based vaccine is associated with a more gradual and tolerogenic response that fosters the crosstalk between platelets and adaptive immunity, the adenovirus-based vaccine, the less immunogenic of the two, evokes an antiviral-like response during which platelets are cleared and less likely to cooperate with B-cells. Moreover, subjects taking aspirin (n=56) display lower antibody levels after BNT162b2 vaccination compared to matched individuals. Conclusions: Platelets are a component of the innate immune pathways that promote the B-cell response after vaccination. Future studies on the platelet-immune crosstalk post-immunization will improve safety, efficacy, and strategic administration of next-generation vaccines

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound\u2010detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross\u2010sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, 120.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40\u2010ligand (P = 0.0238), soluble Nox2\u2010derived peptide (sNox2\u2010dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD40L (Spearman\u2019s rank correlation coefficient [rs], 120.33; P < 0.001), sNox2\u2010dp (rs, 120.57; P < 0.0001), and urinary excretion of isoprostanes (rs, 120.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2\u2010dp, and urinary 8\u2010iso prostaglandin F2\u3b1\u2010III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2\u2010dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

Humanistic and economic impact of moderate to severe plaque psoriasis in Brazil

Introduction Psoriasis is an immune-mediated, chronic, inflammatory disease, which has a substantial humanistic and economic burden. This study aimed to assess the impact of this disease on health-related quality of life (HRQoL), work productivity, and direct and indirect costs from a societal perspective among Brazilian patients. Methods This is a cross-sectional, observational, multicenter study, enrolling patients with moderate to severe plaque psoriasis according to physician evaluation. Data collection was performed from December 2015 to November 2016 through face-to-face interviews using a structured questionnaire and five standardized patient-reported outcomes instruments. Direct costs were estimated by multiplying the amount of resources used (12-month recall period) by the corresponding unit cost. Indirect costs were grouped in two time horizons: annual costs (income reduction and absenteeism) and lifetime costs (demission and early retirement). Results A total of 188 patients with moderate to severe plaque psoriasis were included, with mean age of 48.0 (SD 13.1). “Anxiety and depression” and “pain and discomfort” were the most impaired dimensions, according to the EuroQol Five-Dimension-Three-Level (EQ-5D-3L). The highest effect was found for “symptoms and feelings” [mean (SD) 2.4 (1.7)] Dermatology Life Quality Index (DLQI) subscale. Psoriatic arthritis (PsA) presence and biologic-naïve status were associated with worse HRQoL. Presenteeism was more frequent than absenteeism, according to the Work Productivity and Activity Impairment questionnaire-General Health (WPAI-GH) [17.4% vs. 6.3%], while physical demands and time management were the most affected Work Limitations Questionnaire (WLQ) subscales [means (SD) 23.5 (28.5) and 17.7 (24.9), respectively]. The estimated annual cost per patient was USD 4034. Direct medical costs accounted for 87.7% of this estimate, direct non-medical costs for 2.4%, and indirect costs for 9.9%. Conclusions Results evidenced that moderate to severe plaque psoriasis imposes substantial costs to society. Our data showed that this disease negatively affects both work productivity and HRQoL of Brazilian patients. Subgroups with PsA and biologic-naïve patients presented lower HRQoL, showing the impact of this comorbidity and the relevance of biologics in psoriasis treatment