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ELISA methods comparison for the detection of auto-antibodies against apolipoprotein A1
BACKGROUND:
Autoantibodies against apolipoprotein A1 (anti-apoA1 IgG) have emerged as an independent biomarker for cardiovascular disease and mortality. Across studies, different ELISA methods have been used to measure the level of circulating anti-apoA1 IgG which could lead to substantial result differences between assays.
OBJECTIVES:
To make a comparative study of available anti-apoA1 IgG detection methods and to determine whether the choice of matrix sample (serum vs plasma) could influence the results.
METHODS:
Blood samples were obtained from 160 healthy blood donors and collected on 4 different matrixes (serum, plasma-EDTA, -citrate, -lithium-heparinate). Anti-apoA1 IgG was measured using two homemade (Geneva's and Lisbon's) and one commercial ELISA kits. Passing-Bablok and Bland-Altman were used to compare the results. Anti-apoA1 IgG seropositivity cut-offs were defined according to the user's/manufacturer's criterion.
RESULTS:
The current results showed substantial differences between those 3 assays. The dynamic ranges were significantly different, the commercial kit displaying the narrowest one. Passing-Bablok analysis demonstrated important proportional and constant biases between assays. The anti-apoA1 IgG seropositivity rate in Geneva, Lisbon and commercial assays varied between 24.5% and 1.9%. Matrix comparisons demonstrated that the matrix choice (plasma versus serum) influenced anti-apoA1 IgG results as well as the seropositivity rate in an assay-dependent manner. The coating antigen source was identified as important factor underlying results heterogeneity across assays.
CONCLUSIONS:
These results highlight the impact of the method and the cut-off used on anti-apoA1 IgG results and emphasize the need of standardizing existing assays. Given the important matrix influence, we suggest to use serum as matrix of choice.info:eu-repo/semantics/publishedVersio
Antibiotic therapy in acute pancreatitis: From global overuse to evidence based recommendations.
Although evidence indicates that use of procalcitonin to guide antibiotic decisions for the treatment of acute respiratory infections (ARI) decreases antibiotic consumption and improves clinical outcomes, algorithms used within studies had differences in PCT cut-off points and frequency of testing. We therefore analyzed studies evaluating procalcitonin-guided antibiotic therapy and propose consensus algorithms for different respiratory infection types. Areas covered: We systematically searched randomized-controlled trials (search strategy updated on February 2018) on procalcitonin-guided antibiotic therapy of ARI in adults using a pre-specified Cochrane protocol and analyzed algorithms from 32 trials that included 10,285 patients treated in primary care settings, emergency departments (ED), and intensive care units (ICU). We derived consensus algorithms for use of procalcitonin by the type of ARI including community-acquired pneumonia, bronchitis, chronic obstructive pulmonary disease or asthma exacerbation, sepsis, and post-operative sepsis due to respiratory infection. Consensus algorithm recommendations differ with regard to timing of treatment (i.e. timing of initiation in low-risk patients or discontinuation in high-risk patients) and procalcitonin cut-off points for the recommendation/strong recommendation to discontinue antibiotics (≤ 0.25/≤ 0.1 µg/L in ED and inpatients, ≤ 0.5/≤ 0.25 µg/L in ICU patients, and reduction by ≥ 80% from peak levels in sepsis patients). Expert commentary: Our proposed algorithms may facilitate safe and efficient implementation of procalcitonin-guided antibiotic protocols in diverse healthcare settings. Still, the decision about initiation and cessation of antibiotic treatment remains a clinical decision based on the patient assessment and the severity of illness and use of procalcitonin should not delay empirical treatment in high risk situations.info:eu-repo/semantics/publishedVersio
Lower free triiodothyronine levels within the reference range are associated with higher cardiovascular mortality: An analysis of the NHANES.
BACKGROUND:
Thyroid hormones play a central role in cardiovascular homeostasis. Lower free triiodothyronine (FT3) levels have been associated with worse prognosis in several conditions. However, contrary to thyrotropin (TSH) and free thyroxine (FT4), the role of FT3 in morbidity and mortality in the general population remains uncertain. Our objective was to evaluate the association between within the normal range FT3 levels and mortality in the general population.
METHODS:
We evaluated 7116 adults in the National Health and Nutrition Examination Survey (NHANES) 2001-2002, 2007-2008, and 2009-2010 cycles with mortality evaluated as of December 2011. Exclusion criteria were: pregnancy; history of thyroid disease; use of thyroid-related drugs; and TSH, FT4, or FT3 level outside the reference range.
RESULTS:
During a median follow-up of 45 months, 357 participants died. In unadjusted analysis, lower FT3 levels were associated with higher all-cause (HR per 0.1 pg/mL increase in FT3: 0.82 [95% confidence interval, 0.78-0.87]), cardiovascular (HR 0.74 [0.66-0.83]), cancer-related (HR 0.88 [0.80-0.97]) and other cause-related mortality (HR 0.83 [0.77-0.90]). After adjustment with Cox proportional hazard models, lower FT3 levels remained significantly associated with higher cardiovascular mortality (HR 0.83 [0.75-0.93]), but not with all-cause (HR 0.97 [0.92-1.02]), cancer-related (HR 1.02 [0.89-1.17]), or other cause-related mortality (HR 1.00 [0.92-1.10]).
CONCLUSIONS:
Lower levels of FT3 within the reference range may independently predict higher cardiovascular mortality in the general population.info:eu-repo/semantics/publishedVersio
Olanzapine-Induced Hyperprolactinemia: Two Case Reports.
Background: Hyperprolactinemia is a common consequence of treatment with antipsychotics. It is usually defined by a sustained prolactin level above the laboratory upper level of normal in conditions other than that where physiologic hyperprolactinemia is expected. Normal prolactin levels vary significantly among different laboratories and studies. Several studies indicate that olanzapine does not significantly affect serum prolactin levels in the long term, although this statement has been challenged. Aims: Our aim is to report two olanzapine-induced hyperprolactinemia cases observed in psychiatric consultations. Methods: Medical records of the patients who developed this clinical situation observed in psychiatric consultations in the Psychiatry Department of the Prof. Dr. Fernando Fonseca Hospital during the year of 2017 were analyzed, complemented with a non-systematic review of the literature. Results: The case reports consider two women who developed prolactin-related symptoms after the initiation of olanzapine. No baseline prolactinemia was obtained, and prolactin serum levels were only evaluated after prolactin-related symptoms developed: at the time of its measurement, both patients had been taking olanzapine for more than 24 weeks. Hyperprolactinemia was found to be present in Case 2, whereas Case 1 (a 49-year-old woman) had "normal" serum prolactin levels for premenopausal and prolactin levels slightly above the maximum levels for postmenopausal women. Both patients underwent similar pharmacological adjustments, which comprised switches from olanzapine to aripiprazole. After all pharmacological changes, prolactin serum levels decreased to normal range values and prolactin-related symptoms disappeared. Discussion/Conclusions: Laboratorial and literature prolactinemia values variability and discrepancies may make the management of borderline hyperprolactinemia clinical situations difficult. Baseline prolactin levels should have been obtained, as they help in the management of patients who develop neuroleptic-induced hyperprolactinemia. Prolactin-related symptoms can occur with borderline or normal standardized prolactinemia values. Olanzapine-induced hyperprolactinemia is a rare but possible event. Aripiprazole was used as a suitable alternative for olanzapine-induced hyperprolactinemia.info:eu-repo/semantics/publishedVersio
Staphylococcus aureus nasal carriage among homeless population in Lisbon, Portugal
Methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage is a major risk factor for infection, namely among populations in the community with inherent prompting factors, such as the homeless. In Portugal, there are no data on S. aureus/MRSA nasal carriage among the homeless community. A total of 84 homeless individuals living in Lisbon (34 with no permanent address and 50 living in shelter) were nasally screened for S. aureus/ MRSA. All isolates were characterized to determine antimicrobial susceptibility and clonal type. A total of 43 (51.2%) S. aureus carriers were identified, including a single individual colonized with MRSA (1.2%). S. aureus carriage rate was higher among individuals with no permanent address (58.8% versus 46%), younger (45.7 ± 12.7 versus 52.5 ± 10.8 years), and with diagnosis of asthma (9% versus 0%). The single MRSA belonged to the EMRSA-15 clone (PFGE D, ST15-SCCmec IVh, and spa type t790). Almost half of the methicillin-susceptible S. aureus (MSSA) isolates (41.9%, n = 18) belonged to two major clones, ST398-t1451 (n = 13) and ST30-t399/t11980/t12808 associated with PFGE I (n = 5). A high proportion of isolates showed non-susceptibility to mupirocin (64%), erythromycin (45%), and fusidic acid (20%) and induced resistance to clindamycin (39%). None of the isolates harboured PVL. Our results suggest that the homeless population of Lisbon does not constitute a reservoir of MRSA in the community, but harbour the highly transmissible ST398-t1451 MSSA lineage.info:eu-repo/semantics/publishedVersio
The impact and evolution of acute-on-chronic liver failure in decompensated cirrhosis: A Portuguese single-center study
Acute-on-chronic liver failure (ACLF) is a dynamic syndrome that should be assessed repeatedly. An algorithm for risk stratification in decompensated cirrhosis was recently proposed by the EASL-CLIF (European Association for the Study of the Liver-Chronic Liver Failure) Consortium.
AIM:
To validate the EASL-CLIF Consortium scores in patients with and without ACLF.
MATERIALS AND METHODS:
Retrospective single-center cohort study including patients admitted for acute decompensation of cirrhosis between January 2014 and December 2015, and followed-up until December 2016. We separated patients with and without ACLF and compared the various EASL-CLIF Consortium scores to Child-Pugh and MELD for predicting 28-day (M28), 90-day and 12-month mortality. These scores were recalculated at different time points over 28 days.
RESULTS:
106 patients were included (age 60.3±10.7 years; 87.7% male), 35.8% of whom met ACLF criteria on admission (50%) or during hospitalization. A CLIF-C AD Score ≥60 on admission was associated with a higher risk of developing ACLF. The onset of ACLF during hospitalization portended a poor prognosis. The prognostic performance of the CLIF-C ACLF Score (AUROC for M28: 0.856±0.071) was globally comparable to that of Child-Pugh and MELD. Overall, ACLF resolved in 54.1% patients, resulting in increased survival. Almost 40% of the patients reached their final ACLF grade after ≥8 days, with 13.9% of ACLF patients experiencing resolution by then.
DISCUSSION:
We confirmed the accuracy and clinical value of the several proposed scores in our population. Prognosis was better defined by the early clinical course than by the initial evaluation, emphasizing the importance of repeated assessments.info:eu-repo/semantics/publishedVersio
Pituitary Apoplexy May Be Mistaken for Temporal Arteritis
Pituitary apoplexy is a rare endocrine emergency, characterized by a sudden increase in pituitary gland volume secondary to acute ischaemic infarction or haemorrhage of the pituitary gland, usually in the presence of a pituitary adenoma. We present the case of a 79-year-old man admitted for new-onset, bi-temporal and severe headache, associated with photophobia and vomiting, whose additional study revealed pituitary apoplexy. This case highlights the need for high clinical suspicion of this rare entity in order to reduce the associated mortality.info:eu-repo/semantics/publishedVersio
Mercapturate Pathway in the Tubulocentric Perspective of Diabetic Kidney Disease
BACKGROUND: The recent growing evidence that the proximal tubule underlies the
early pathogenesis of diabetic kidney disease (DKD) is unveiling novel and
promising perspectives. This pathophysiological concept links tubulointerstitial
oxidative stress, inflammation, hypoxia, and fibrosis with the progression of
DKD. In this new angle for DKD, the prevailing molecular mechanisms on proximal
tubular cells emerge as an innovative opportunity for prevention and management
of DKD as well as to improve diabetic dysmetabolism.
SUMMARY: The mercapturate pathway (MAP) is a classical metabolic detoxification
route for xenobiotics that is emerging as an integrative circuitry detrimental to
resolve tubular inflammation caused by endogenous electrophilic species. Herein
we review why and how it might underlie DKD. Key Messages: MAP is a hallmark of
proximal tubular cell function, and cysteine-S-conjugates might represent targets
for early intervention in DKD. Moreover, the biomonitoring of urinary
mercapturates from metabolic inflammation products might be relevant for the
implementation of preventive/management strategies in DKD.info:eu-repo/semantics/publishedVersio