Do patient-related blood donors represent a threat to the safety of the blood supply?

BACKGROUND AND OBJECTIVES: Patient-related blood donors contribute to a significant proportion of the blood units collected in hospital-based blood banks. However, there is some concern on the safety of this kind of donation because of the possible existence of incentives for the donor to conceal deferrable risk factors, thus increasing the risk of donation within the window-period of transfusion-transmitted infections. We tested the hypothesis that if patient-related blood donors are less safe than community ones, the former would display both a higher prevalence of viral markers and a predominance of undisclosed risk-factors with low social acceptability. DESIGN AND METHODS: Comparison of virus reactivity rates against hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV), and the associated risk-factors, between patient-related and community donors who donated whole blood in our center during a five-year period. RESULTS: During the period under study 72,226 donors gave 149,944 whole blood units, of which 22,888 (15.3%) were provided by patient-related donors. There were 273 confirmed virus-reactive donations (15 anti-HIV, 148 anti-HCV and 110 HBsAg). The adjusted prevalence of virus reactivity was 19 (95% CI: 11-35) times higher in first-time donors than in repeat donors, 3.5 (95% CI: 2.3-4.1) times higher in donors > or = 30 years old than in younger ones, and 2.5 (95% CI: 1.9-3.2) times higher in patient-related donors than in community donors. With regard to deferrable risk-factors not disclosed at the time of donation, there was no significant difference between patient-related and community donors in the frequency of people who denied any risk-factor or who admitted intravenous drug use or high-risk sex. Past household contact with individuals having liver disease was significantly more frequent in patient-related donors than in community ones. INTERPRETATION AND CONCLUSIONS: Our results do not support the hypothesis that patient-related donors represent an increased risk of window-period donation because they conceal deferrable risk factors more frequently than community donors.     

Targeting virulence not viability in the search for future antibacterials

New antibacterials need new approaches to overcome the problem of rapid antibiotic resistance. Here we review the development of potential new antibacterial drugs that do not kill bacteria or inhibit their growth, but combat disease instead by targeting bacterial virulence.     

Syncope in Patients With Severe Aortic Stenosis: More Than Just an Obstruction Issue

BackgroundSevere aortic stenosis (AoS) is considered a primary cause of syncope. However, other mechanisms may be present in these patients and accurate diagnosis can have important clinical implications. The aim of this study is to assess the different etiologies of syncope in patients with severe AoS and the impact on prognosis of attaining a certain or highly probable diagnosis for the syncope.MethodsOut of a cohort of 331 patients with AoS and syncope, 61 had severe AoS and were included in the study. Main cause of syncope and adverse cardiac events were assessed.ResultsIn 40 patients (65.6%), we reached a certain or highly probable diagnosis of the main cause of the syncope. AoS was considered the primary cause of the syncope in only 7 patients (17.5% of the patients with known etiology). Atrioventricular block (14 patients, 35.0%) and vasovagal syncope (6 patients, 15.0%) were the most frequently diagnosed causes. The presence of a known cause for syncope during the admission was not associated with a lower incidence of recurrence during follow-up (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.20-2.40). Syncope of unknown etiology was independently associated with greater mortality during 1-year follow-up (HR 5.4, 95% CI 1.3-21.6) and 3-year follow-up (HR 3.5, 95% CI 1.2-10.3).ConclusionsIn a high proportion of patients with severe AoS admitted for syncope, the valvulopathy was not the main cause of the syncope. Syncope in two-thirds of this population was caused by either bradyarrhythmia or reflex causes. Syncope of unknown cause was associated with increased short- and medium-term mortality, independently from treatment of the valve disease. An exhaustive work-up should be conducted to determine the main cause for syncope.     

A Novel Regulatory Defect in the Branched‐Chain α‐Keto Acid Dehydrogenase Complex Due to a Mutation in the PPM1K Gene Causes a Mild Variant Phenotype of Maple Syrup Urine Disease

This article describes a hitherto unreported involvement of the phosphatase PP2Cm, a recently described member of the branched‐chain α‐keto acid dehydrogenase (BCKDH) complex, in maple syrup urine disease (MSUD). The disease‐causing mutation was identified in a patient with a mild variant phenotype, involving a gene not previously associated with MSUD. SNP array‐based genotyping showed a copy‐neutral homozygous pattern for chromosome 4 compatible with uniparental isodisomy. Mutation analysis of the candidate gene, PPM1K, revealed a homozygous c.417_418delTA change predicted to result in a truncated, unstable protein. No PP2Cm mutant protein was detected in immunocytochemical or Western blot expression analyses. The transient expression of wild‐type PPM1K in PP2Cm‐deficient fibroblasts recovered 35% of normal BCKDH activity. As PP2Cm has been described essential for cell survival, apoptosis and metabolism, the impact of its deficiency on specific metabolic stress variables was evaluated in PP2Cm‐deficient fibroblasts. Increases were seen in ROS levels along with the activation of specific stress‐signaling MAP kinases. Similar to that described for the pyruvate dehydrogenase complex, a defect in the regulation of BCKDH caused the aberrant metabolism of its substrate, contributing to the patient's MSUD phenotype—and perhaps others.     

Prognostic value and clinical predictors of intramyocardial hemorrhage measured by CMR T2* sequences in STEMI

The International Journal of Cardiovascular Imaging - Recent studies show that microvascular injury consists of microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH). In patients...     

PET/TC con 18F-FDG en la sospecha de infección asociada a dispositivos intracardiacos: rendimiento y utilidad diagnóstica

Introduction and objectivesCardiac device-related infections (CDRI) may be life-threatening and require early and accurate diagnosis. The aims of this study were to analyze the performance of positron emission tomography-computed tomography (PET/CT) in suspected CDRI, to assess changes to the initial diagnosis, and to identify a clinical subgroup deriving the greatest benefit from this imaging modality.MethodsRetrospective study including patients evaluated by PET/CT for suspected CDRI from 2011 to 2018. We assessed PET/CT performance and the agreement between the initial, post-PET and definitive diagnoses. We also assessed changes in the diagnosis, depending on initial clinical suspicion, to identify patients deriving the greatest benefit from PET/CT.ResultsWe included 44 patients. The prevalence of endocarditis was 57%. The sensitivity and specificity of PET/CT for the diagnosis of infective endocarditis were 0.84 and 0.95, respectively. Post-PET diagnosis improved the initial diagnosis by 45%. PET/CT correctly reclassified 57% of patients with initial suspicion of generator pocket infection by detecting lead infection.ConclusionsPET/CT showed high diagnostic performance in suspected of CDRI and significantly improved the conventional diagnostic approach, especially in patients with initial suspicion of focal infection.     

Down-regulation of FLIP sensitizes rheumatoid synovial fibroblasts to Fas-mediated apoptosis

OBJECTIVE: Hyperplasia of fibroblast-like synoviocytes (FLS) contributes to chronic inflammation and joint destruction in rheumatoid arthritis (RA). FLICE-inhibitory protein (FLIP) is an antiapoptotic protein that might prevent apoptotic elimination of FLS in response to death ligands such as tumor necrosis factor alpha (TNFalpha) or Fas ligand, which are present in RA synovium. Previous studies on FLIP expression by osteoarthritis (OA) and RA FLS have shown variable results, and the specific role of FLIP as an apoptosis inhibitor in these cells remains unclear. We undertook this study to investigate the expression and antiapoptotic function of FLIP in FLS. METHODS: We studied the expression of FLIP by immunohistochemistry and immunoblotting in synovial tissues or cultured FLS from RA and OA patients. FLS apoptosis was induced by an agonistic anti-Fas monoclonal antibody and FLS were then quantified. We studied the effects of cycloheximide (CHX), TNFalpha, and FLIP antisense oligonucleotide on FLIP expression and FLS apoptotic susceptibility. RESULTS: FLIP(L) was the isoform mainly expressed in lining synoviocytes and cultured FLS. Synovial tissues and cultured FLS from OA and RA tissues displayed similar patterns and levels of expression of FLIP. Fas-induced apoptosis was variable in different FLS lines, but differences between OA and RA groups were not detected. TNFalpha induced increases in FLIP(L) and FLIP(S) expression and protected RA FLS from apoptosis, while CHX induced the opposite effects. Down-regulation of FLIP by antisense oligonucleotide strongly sensitized RA FLS to Fas-mediated apoptosis. CONCLUSION: Apoptosis susceptibility and FLIP expression are similar in OA and RA FLS. Down-regulation of FLIP sensitizes RA FLS to Fas-mediated apoptosis and may be a valuable tool for targeting RA FLS hyperplasia.     

Descriptive study of the patients treated at the clinic “Integrated Dentistry for Patients with Special Needs” at Complutense University of Madrid (2003-2012)

Objectives: To study clinical and epidemiological characteristics of the patients treated at the clinic “Integrated Dentistry for Patients with Special Needs (Special Care Dentistry)” at Complutense University of Madrid (UCM), as well as to know the dental treatments performed in these patients and the modifications from the usual treatment protocol. The information obtained from the results could also be applied in order to assess the needs of dental students education about this type of patients. Study Design: Medical records review of all the patients referred to the clinic of “Integrated Dentistry for Patients with Special Needs”, performing a retrospective cross-sectional study analyzing their main pathology, ASA risk score (Classification system used by the American Society of Anesthesiologists to estimate the risk posed by the anesthesia for various patient conditions), pharmacological treatment, what kind of dental treatment was necessary, whether the patient was treated or not, and if it was required to change any procedure due to the patient health status (sedation or antibiotic prophylaxis). Results: The number of patients referred to the clinic was 447, of whom 426 were included in this study. Out of them, 52,35 % were men and 47,89 were women, with a mean age of 49,20 years. More frequent pathologies were cardiovascular or cerebrovascular diseases (24,29 %), infectious diseases (12,41%), endocrine diseases (11,66%) and intellectual disability (8,85%). 70’18% of the patients were treated, with sedation being necessary in 9,03% of the cases and antibiotic prophylaxis in 11,70%. Conclusions: Given the high number of patients with some kind of pathology and the amount of medicines that they use, it seems necessary for dentistry students to have a specific training regarding how to handle and treat these patients, so they will be able to provide them the best possible care. Key words:Patients with special needs, medically compromised patients, dental treatment, special care dentistry.     

Metabolomic fingerprint reveals that metformin impairs one-carbon metabolism in a manner similar to the antifolate class of chemotherapy drugs

Metabolomic fingerprint of breast cancer cells treated with the antidiabetic drug metformin revealed a significant accumulation of 5-formimino-tetrahydrofolate, one of the tetrahydrofolate forms carrying activated one-carbon units that are essential for the de novo synthesis of purines and pyrimidines. De novo synthesis of glutathione, a folate-dependent pathway interconnected with one-carbon metabolism was concomitantly depleted in response to metformin. End-product reversal studies demonstrated that thymidine alone leads to a significant but incomplete protection from metformin's cytostatic effects. The addition of the substrate hypoxanthine for the purine salvage pathway produces major rightward shifts in metformin's growth inhibition curves. Metformin treatment failed to activate the DNA repair protein ATM kinase and the metabolic tumor suppressor AMPK when thymidine and hypoxanthine were present in the extracellular milieu. Our current findings suggest for the first time that metformin can function as an antifolate chemotherapeutic agent that induces the ATM/AMPK tumor suppressor axis secondarily following the alteration of the carbon flow through the folate-related one-carbon metabolic pathways.