First-line thalidomide-dexamethasone therapy in preparation for autologous stem cell transplantation in young patients (<61 years) with symptomatic multiple myeloma

Thalidomide-dexamethasone therapy was given in patients (<61 years) with previously untreated symptomatic multiple myeloma. The aim of this study was to assess the efficacy and toxicity of this combination as first-line therapy, and to determine its effect on stem cell collection and engraftment. During first-line therapy, thalidomide and dexamethasone were administered for 75 days (200 mg/day) and 3 months, respectively. The monthly dose of dexamethasone was 20 mg/m2/day for 4 days, with cycles repeated on days 9 to 12 and 17 to 20 on the first and the third month of therapy. After first-line therapy, a collection of peripheral blood stem cells (PBSC) was performed. Between May 2003 and September 2004, 60 patients were included. On an intent-to-treat basis, the overall response (> or =partial response) rate was 74%, including 24% of patients who obtained a complete remission. Grade 3-4 toxicities consisted of infections (12%), deep-vein thrombosis (3%), constipation (5%), and neuropathy (5%). A total of 58 patients (96%) proceeded to PBSC mobilisation and yielded a median number of 8 x 10(6) CD34+ cells/kg. First-line thalidomide-dexamethasone therapy is effective and relatively well tolerated in young patients with symptomatic multiple myeloma. This combination does not affect PBSC mobilisation.     

Protective effect of chronic caffeine intake on gene expression of brain derived neurotrophic factor signaling and the immunoreactivity of glial fibrillary acidic protein and Ki-67 in Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive degeneration of the hippocampal and cortical neurons. This study was designed to demonstrate the protective effect of caffeine on gene expression of brain derived neurotrophic factor (BDNF) and its receptor neural receptor protein-tyrosine kinase-β (TrkB) as well as glial fibrillary acidic protein (GFAP) and Ki-67 immunoreactivity in Aluminum chloride (AlCl₃) induced animal model of AD. Fifty adult rats included in this study were classified into 5 group (10 rats each); negative and positive control groups (I&II), AD model group (III), group treated with caffeine from the start of AD induction (IV) and group treated with caffeine two weeks before AD induction (V). Hippocampal tissue BDNF and its receptor (TrkB) gene expression by real time RT-PCR in addition to immunohistochemical study of GFAP and Ki67 immunoreactivity were performed for all rats in the study. The results of this study revealed that caffeine has protective effect through improving the histological and immunohistochemical findings induced by AlCl₃ as well as BDNF and its receptor gene expression. It could be concluded from the current study, that chronic caffeine consumption in a dose of 1.5 mg/kg body weight daily has a potentially good protective effect against AD.     

Pneumocystis jiroveci prophylaxis in patients undergoing Bendamustine treatment: the need for a standardized protocol

The decision for PJP prophylaxis depends on a physician's evaluation of multiple variables. The high rate of PJP infection described in this article combined with the known impaired T‐cell function post Bendamustine treatment justifies considering all patients for PJP prophylaxis when they receive Bendamustine treatment.     

Fulminant onset of acute leukemia from normal hematopoiesis within 3 months of follow up for multiple myeloma treated with total therapy protocols

Assiduous surveillance for genetic aberrations is necessary in patients on cytotoxic therapies to detect therapy‐related myeloid neoplasms (t‐MN). Current modalities include metaphase cytogenetics and FISH. Since t‐MN may develop abruptly in cytogenetically normal patients, a discussion exploring additional methods such as SNP‐array and targeted‐deep‐sequencing to detect subchromosomal abnormalities is needed.     

Outcome of gastric antral vascular ectasia and related anemia after orthotopic liver transplantation

BACKGROUNDGastric antral vascular ectasia (GAVE) is a significant complication of cirrhosis. Numerous medical, surgical, and endoscopic treatment modalities have been proposed with varied satisfactory results. In a few small studies, GAVE and associated anemia have resolved after orthotopic liver transplantation (OLT). AIMTo assess the impact of OLT on the resolution of GAVE and related anemia.METHODSWe retrospectively reviewed clinical records of adult patients with GAVE who underwent OLT between September 2012 and September 2019. Demographics and other relevant clinical findings were collected, including hemoglobin levels and upper endoscopy findings before and after OLT. The primary outcome was the resolution of GAVE and its related anemia after OLT.RESULTSSixteen patients were identified. Mean pre-OLT Hgb was 7.7 g/dL and mean 12 mo post-OLT Hgb was 11.9 g/dL, (P = 0.001). Anemia improved (defined as Hgb increased by 2g) in 87.5% of patients within 6 to 12 mo after OLT and resolved completely in half of the patients. Post-OLT esophagogastroduodenoscopy was performed in 10 patients, and GAVE was found to have resolved entirely in 6 of those patients (60%). CONCLUSIONAlthough GAVE and associated anemia completely resolved in the majority of our patients after OLT, GAVE persisted in a few patients after transplant. Further studies in a large group of patients are necessary to understand the causality of disease and to better understand the factors associated with the persistence of GAVE post-transplant.     

Indirect effects of cigarette butt waste on the dengue vector Aedes aegypti (Diptera: Culicidae)

Despite major insecticide-based vector control programs, dengue continues to be a major threat to public health in urban areas. The reasons for this failure include the emergence of insecticide resistance and the narrowing of the spectrum of efficient products. Cigarette butts (CBs), the most commonly discarded piece of waste, also represent a major health hazard to human and animal life. CBs are impregnated with thousands of chemical compounds, many of which are highly toxic and none of which has history of resistance in mosquitoes. This study was performed to examine whether exposure to CB alters various biological parameters of parents and their progeny. We examined whether the mosquito changes its ovipositional behaviors, egg hatching, reproductive capacity, longevity and fecundity in response to CB exposure at three different concentrations. Females tended to prefer microcosms containing CBs for egg deposition than those with water only. There were equivalent rates of eclosion success among larvae from eggs that matured in CB and water environments. We also observed decreased life span among adults that survived CB exposure. Extracts of CB waste have detrimental effects on the fecundity and longevity of its offspring, while being attractive to its gravid females. These results altogether indicate that CB waste indirectly affect key adult life traits of Aedes aegypti and could conceivably be developed as a novel dengue vector control strategy, referring to previously documented direct toxicity on the larval stage. But this will require further research on CB waste effects on non-target organisms including humans.     

Hypofibrinolysis in type 2 diabetes: the role of the inflammatory pathway and complement C3

Aims/hypothesis

Plasminogen activator inhibitor-1 (PAI-1) has been regarded as the main antifibrinolytic protein in diabetes, but recent work indicates that complement C3 (C3), an inflammatory protein, directly compromises fibrinolysis in type 1 diabetes. The aim of the current project was to investigate associations between C3 and fibrinolysis in a large cohort of individuals with type 2 diabetes.

Methods

Plasma levels of C3, C-reactive protein (CRP), PAI-1 and fibrinogen were analysed by ELISA in 837 patients enrolled in the Edinburgh Type 2 Diabetes Study. Fibrin clot lysis was analysed using a validated turbidimetric assay.

Results

Clot lysis time correlated with C3 and PAI-1 plasma levels (r?=?0.24, p?<?0.001 and r?=?0.22, p?<?0.001, respectively). In a multivariable regression model involving age, sex, BMI, C3, PAI-1, CRP and fibrinogen, and using log-transformed data as appropriate, C3 was associated with clot lysis time (regression coefficient 0.227 [95% CI 0.161, 0.292], p?<?0.001), as was PAI-1 (regression coefficient 0.033 [95% CI 0.020, 0.064], p?<?0.05) but not fibrinogen (regression coefficient 0.003 [95% CI ?0.046, 0.051], p?=?0.92) or CRP (regression coefficient 0.024 [95% CI ?0.008, 0.056], p?=?0.14). No correlation was demonstrated between plasma levels of C3 and PAI-1 (r?=??0.03, p?=?0.44), consistent with previous observations that the two proteins affect different pathways in the fibrinolytic system.

Conclusions/interpretation

Similarly to PAI-1, C3 plasma levels are independently associated with fibrin clot lysis in individuals with type 2 diabetes. Therefore, future studies should analyse C3 plasma levels as a surrogate marker of fibrinolysis potential in this population.     

Prevalence of Metabolic Syndrome in Elderly and Agreement among Four Diagnostic Criteria

Background

Metabolic syndrome (MS) is an aggregation of risk factors that increase the incidence of cardiovascular events and diabetes mellitus (DM). Population aging is accompanied by higher prevalence of MS, which varies depending on the population studied and the diagnostic criteria used.

Objective

To determine prevalence of MS in the elderly using four diagnostic criteria and agreement between them.

Methods

Cross-sectional study on 243 patients older than 60 years (180 women) in Niterói, RJ. They were evaluated by clinical examination, fasting glucose, fasting insulin, lipid profile and anthropometric measurements - weight, height, waist circumference and waist/hip ratio. Prevalence of MS was estimated by World Health Organization (WHO) modified, National Cholesterol Education Program - Adult Treatment Panel III (NCEP-ATP III), International Diabetes Federation (IDF) and Joint Interim Statement (JIS) criteria.

Results

Prevalence was high with the four criteria WHO (51.9%), NCEP-ATPIII (45.2%), IDF (64.1%) and JIS (69.1%), and agreement between criteria by kappa was moderate in almost all comparisons WHO vs. IDF (k = 0.47;95% confidence interval (CI), 0.35 to 0.58); WHO vs. NCEP-ATPIII (k = 0.51; 95% CI, 0.40 to 0.61); WHO vs. JIS (k = 0.45; 95% CI, 0.33 to 0.56); IDF vs. NCEP-ATPIII (k = 0.55; 95% CI, 0.45 to 0.65) and NCEP-ATPIII vs. JIS (k = 0.53; 95% CI, 0.43-0.64), except between IDF vs. JIS (K = 0.89;95% CI, 0.83 to 0.95), which was considered good.

Conclusion

Prevalence of MS was high with the four diagnostic criteria, mainly by JIS. There was good agreement between JIS and IDF criteria and moderate among the others.