Ischemic stroke (IS) or transient ischemic attack (TIA) history is present in 4-17% of patients with coronary artery disease (CAD). This subgroup of patients is at high risk for both ischemic and ...bleeding events. The aim of this study was to determine the role of platelet aggregability, coagulation and endogenous fibrinolysis in patients with CAD and previous IS or TIA.
A prospective case-control study that included 140 stable CAD patients divided into two groups: the CASE group (those with a previous IS/TIA, n=70) and the CONTROL group (those without a previous IS/TIA, n=70). Platelet aggregability (VerifyNow Aspirin® and VerifyNow P2Y12®), coagulation (fibrinogen and thromboelastography by Reorox®) and endogenous fibrinolysis (D dimer and plasminogen activator inhibitor-1) were evaluated.
Patients in the CASE group presented significantly higher systolic blood pressure levels (135.84±16.09 vs 123.68±16.11, p<0.01), significantly more previous CABG (25.71% vs 10%, p=0.015) and significantly higher calcium channel blocker usage (42.86% vs 24.29%, p=0.02) than those in the control group. In the adjusted models, low triglyceride values, low hemoglobin values and higher systolic blood pressure were significantly associated with previous IS/TIA (CASE group). Most importantly, platelet aggregability, coagulation and fibrinolysis tests were not independently associated with previous cerebrovascular ischemic events (CASE group).
Platelet aggregability, coagulation and endogenous fibrinolysis showed similar results among CAD patients with and without previous IS/TIA. Therefore, it remains necessary to identify other targets to explain the higher bleeding risk presented by these patients.
•Caplacizumab reduces exacerbation and refractoriness in iTTP.•As initial therapy, caplacizumab accelerates response and reduces the need for PEX and hospital stay.
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Immune thrombotic ...thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. The objective of this study was to analyze and compare the safety and efficacy of caplacizumab vs the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 patients with iTTP (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5%; P < .05) and less refractoriness (4.5% vs 14.1%; P < .05) than those who were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after PEX was associated with a lower number of PEX (odds ratio, 7.5; CI, 2.3-12.7; P < .05) and days of hospitalization (odds ratio, 11.2; CI, 5.6-16.9; P < .001) compared with standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared with the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared with standard of care regimens. When administered within the first 3 days after PEX, it also provided a faster clinical response, reducing hospitalization time and the need for PEX.
Proton-pump inhibitors (PPIs) are often prescribed to patients receiving dual antiplatelet therapy (DAPT). However, this class of medication, especially omeprazole, has been associated with a ...reduction in clopidogrel efficacy, leading many clinicians to substitute omeprazole with ranitidine.
Our objective was to compare the antiplatelet effect of clopidogrel before and after the addition of omeprazole or ranitidine.
We measured platelet aggregability at baseline and after 1 week of clopidogrel 75 mg daily. Subjects were then randomized in a double-blinded, double-dummy fashion to omeprazole 20 mg twice daily (bid) or ranitidine 150 mg bid. We repeated aggregability tests after 1 additional week, using VerifyNow P2Y12™ (Accumetrics; San Diego, CA, USA), depicting aggregability as percent inhibition of platelet aggregation (IPA).
We enrolled 41 patients in the omeprazole group and 44 in the ranitidine group. IPA was significantly decreased after the addition of omeprazole to clopidogrel (from 26.3 ± 32.9 to 17.4 ± 33.1 %; p = 0.025), with no statistical significant changes observed in the ranitidine group (from 32.6 ± 28.9 to 30.1 ± 31.3 %; p = 0.310). The comparison of IPA in both groups at the end of the follow-up showed a trend toward significance (p = 0.07, 95 % confidence interval CI -1.19 to 26.59); after excluding homozygous patients for 2C19*2 genotype, the comparison of IPA between the groups reached statistical significance (32.7 ± 30.8 vs. 17.7 ± 33.4 %, respectively, for ranitidine and omeprazole groups; p = 0.04).
Unlike omeprazole, ranitidine did not influence platelet aggregability response to clopidogrel.
NCT01896557.
Progressive multifocal leukoencephalopathy (PML) is a feared entity that occurs most frequently in conditions of extreme immunodeficiency. The diagnosis is often made long after the onset of symptoms ...due to the physicians' unfamiliarity, and the unavailability of diagnostic tests in some medical centers. Although the incidence of PML is decreasing among HIV patients with the advent of highly active antiretroviral therapy (HAART), in Brazil this entity is the fourth highest neurological complication among these patients. The authors present the case of a middle-aged man who tested positive for HIV concomitantly with the presentation of hyposensitivity in the face and the right side of the body, accompanied by mild weakness in the left upper limb. The clinical features worsened rapidly within a couple of weeks. The diagnostic work-up pointed to the working diagnosis of PML after brain magnetic resonance imaging; however, the detection of the John Cunningham virus (JCV) in the cerebral spinal fluid was negative. HAART was started but the patient died after 7 weeks of hospitalization. The autopsy revealed extensive multifocal patchy areas of demyelination in the white matter where the microscopy depicted demyelination, oligodendrocytes alterations, bizarre atypical astrocytes, and perivascular lymphocytic infiltration. The immunohistochemistry was positive for anti-SV40, and the polymerase chain reaction of the brain paraffin-embedded tissue was positive for JCV. The authors highlight the challenges for diagnosing PML, as well as the devastating outcome of PML among HIV patients.
Neem tree (Azadirachta indica A. Juss. fam. Meliaceae) has been extensively employed to combat diverse pathologies. Moreover, it has been described that its leaf extract present anticarcinogenic ...action. Thus, the neem extract (NE) chemical and antioxidant properties was evaluated, and also, the capacity of two dermatological formulations incorporated with neem extract (F1 and F2) to avoid oxidative UVB-induced skin injury in hairless mice. NE constituents were investigated and free radical scavenging ability were determined by different methods in vitro. Skin from mice treated with F1 and F2 and submitted to UVB radiation were tested for different parameters of inflammation and oxidative injury. Results show that the NE polyphenol and flavonoid content were 135.30 and 37.12mg/g, respectively. High performance liquid chromatography (HPLC) results demonstrated the existence of azarachtin, rutin, ursolic acid and tannic acid. NE presented scavenging ability by ABTS radical, ferric-reducing antioxidant power (FRAP), inhibition of lipid peroxidation and iron chelation. In vivo, it was observed that mice treated with F1 and F2 showed amelioration of the inflammation by reducing UVB induced skin edema. However, only samples from animals treated with F1 had lower neutrophil recruitment (measured by myeloperoxidase activity), and returning the oxidative status to baseline levels in parameters such as reduced glutathione level, ferric reducing ability (FRAP), and scavenging of free radical (ABTS). Concluding, NE demonstrated a good antioxidant property in vitro, and the data suggest the use of NE added F1 to prevent skin damage caused by UVB irradiation.
This study was designed to analyse the morphological changes and dystrophin expression on heart of animals undergoing sepsis induced by cecal ligation and puncture (CLP) followed by pneumonia. Male ...C57/Bl6 mice were subjected to sham or moderated septic injury induced by CLP. Three days post‐CLP, surviving mice were subjected to a second hit with Pseudomonas aeruginosa (Pa). Twenty‐four hours after pneumonia induction we evaluated the bacterial count and cytokines levels in BAL and serum and the morphology and dystrophin expression in the heart of animals. We observed an increased number of bacteria in the BAL of Sham+Pa and CLP+Pa groups but not in the serum of mice. Sham+Pa and CLP+Pa animals presented significantly increased levels of IL‐6 and KC in both BAL and serum. Myocardium of CLP+Pa mice presented increased foci of myocytolysis and tumefaction of cardiac cells as compared to CLP+Sal myocardium. Consonantly, reduced amounts of dystrophin were detected in CLP+Sal myocardium as compared to controls; however, dystrophin loss was more pronounced in myocardium of septic mice subjected “two‐hit”. Mortality was severely increased after second hit as compared with mice receiving CLP or pneumonia alone, suggesting that second hit worsen the survival.This is the first study evaluating dystrophin loss/disruption in two‐hit sepsis model (that more closely mimics the clinical scenario secondary infection). Additional studies are needed to further elucidate these myocardial structural changes in sepsis given the continued impact of cardiovascular involvement and the risks of secondary infection on mortality.
Background
Vitamin D deficiency has been linked to numerous health issues, including an increased risk of hip fractures. This meta‐analysis aimed to investigate the relationship between vitamin D ...deficiency and mortality in patients with hip fracture. To assess the impact of different levels of vitamin D deficiency on mortality in patients with hip fractures and examine the influence of potential confounding factors.
Methods
A systematic search of PubMed, EMBASE, Scopus, and Cochrane Collaboration Library was conducted, resulting in nine eligible cohort studies (n = 4409). Patients with hip fractures were categorized based on their vitamin D levels as severe, moderate, or insufficient. Mortality was the primary outcome measure in this study. Subgroup analyses were performed according to the follow‐up time. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random‐effects model in Review Manager 5.4.
Results
Nine studies, with a pool of 4409 patients, were included. Vitamin D insufficiency was significantly associated with increased mortality (OR 1.24, 95% CI 1.05–1.46; I2 = 4%). Severe deficiency also led to a significant increase in mortality (OR 2.08, 95% CI 1.09–3.97; I2 = 42%), whereas moderate deficiency did not show a significant effect (OR 1.06, 95% CI 0.79–1.44; I2 = 0%). Subgroup analysis revealed significant associations between vitamin D insufficiency and increased mortality at 1‐year (OR 1.37, 95% CI 1.06–1.77) and 2‐year follow‐ups (OR 1.78, 95% CI 1.01–3.15). After adjusting for potential confounders, no significant increase in the mortality rate was observed.
Conclusions
This meta‐analysis suggests that vitamin D insufficiency and severe deficiency are associated with increased mortality in patients with hip fracture. However, after adjusting for confounding factors, this association was not statistically significant. Further research is necessary to understand the role of vitamin D deficiency in this population.
Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by progressive loss of spinal and cortical motor neurons, leading to muscular atrophy, ...respiratory failure, and ultimately death. There is no known cure, and the clinical benefit of the two drugs approved to treat ALS remains unclear. Novel disease-modifying therapeutics that are able to modulate the disease course are desperately needed. Our objective was to evaluate the efficacy and tolerability of Elysium Health's candidate drug EH301 in people with ALS (PALS). Methods: This was a single-center, prospective, double-blind, randomized, placebo-controlled pilot study. Thirty-two PALS were recruited thanks to the collaboration of the Spanish Foundation for ALS Research (FUNDELA). Study participants were randomized to receive either EH301 or placebo and underwent evaluation for 4 months. Differences between EH301 and placebo-treated participants were evaluated based on standard clinical endpoints, including the revised ALS functional rating scale (ALSFRS-R), forced vital capacity (FVC), and the Medical Research Council (MRC) grading scale. Results: Compared to placebo, participants treated with EH301 demonstrated significant improvements in the ALSFRS-R score, pulmonary function, muscular strength, and in skeletal muscle/fat weight ratio. EH301 was shown to significantly slow the progression of ALS relative to placebo, and even showed improvements in several key outcome measures compared with baseline. Conclusions: This study provides evidence in support of the disease-modifying effects of EH301 for the treatment of ALS.
Trial registration:
ClinicalTrials.gov identifier: NCT03489200.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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