Fournierbengtson2676

There is accumulating data suggesting that periodontitis is associated with increased risk of systemic and autoimmune diseases, including cardiovascular disease, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and there is an unmet need to identify these individuals early. With the periodontal bacteria Porphyromonas gingivalis (Pg) as one of the key drivers of periodontitis, we set out to investigate whether antibodies to Pg virulence factor arginine gingipain (Rgp) could serve as a biomarker for periodontitis patients at increased risk of autoimmunity and systemic disease. We measured serum anti-Rgp IgG in three study populations PAROKRANK (779 individuals with myocardial infarction (MI); 719 controls), where 557 had periodontitis, and 312 were positive for autoantibodies associated with RA/SLE; the PerioGene North pilot (41 periodontitis; 39 controls); and an SLE case/control study (101 SLE; 100 controls). Anti-Rgp IgG levels were increased in severe periodontitis compared to controls (p less then 0.0001), in individuals positive for anti-citrullinated protein antibodies (p = 0.04) and anti-dsDNA antibodies (p = 0.035), compared to autoantibody-negative individuals; and in MI patients versus matched controls (p = 0.035). Our data support longitudinal studies addressing the role of anti-Rgp antibodies as biomarkers for periodontitis patients at increased risk of developing autoimmunity linked to RA and SLE, and mechanisms underpinning these associations.

Immune dysregulation and hypoxemia are two important pathophysiological problems in patients with COVID-19 that affect peripheral blood count parameters. We hypothesized that assessment of the neutrophil-lymphocyte ratio (NLR) and red blood cell distribution width index (RDW-SD) could predict death in patients with severe and critical COVID-19.

Seventy patients admitted to the intensive care unit (ICU) for COVID-19 acute respiratory failure were included in the study. RDW-SD and NLR on the day of ICU admission and peak values during the entire hospitalization were assessed. The primary endpoint was death before ICU discharge.

Patients who died had higher NLR on admission (20.3, IQR 15.3-30.2 vs. 11.0, IQR 6.8-16.9;

= 0.003) and higher RDW-SD (48.1 fL; IQR 43.1-50.5 vs. 43.9 fL; IQR 40.9-47.3,

= 0.01) than patients discharged from the ICU. NLR and RDW-SD values on ICU admission accurately predicted death in 76% (AUC = 0.76; 95%CI 0.65-0.86;

= 0.001; cut-off > 14.38) and 72% of cases (AUC = 0.72; 95%CI 0.60-0.82;

= 0.003; cut-off > 44.7 fL), respectively. Multivariable analysis confirmed that NLR > 14.38 on the day of ICU admission was associated with a 12-fold increased risk of death (logOR 12.43; 95%CI 1.61-96.29,

= 0.02), independent of other blood counts, clinical and demographic parameters.

Neutrophil-lymphocyte ratio determined on the day of ICU admission may be a useful biomarker predicting death in patients with severe and critical COVID-19.

Neutrophil-lymphocyte ratio determined on the day of ICU admission may be a useful biomarker predicting death in patients with severe and critical COVID-19.Adalimumab is currently the only biological medicine approved by the FDA for the treatment of hidradenitis suppurativa (HS). The breakout of biosimilar drugs made them more accessible due to their impact on pharmacoeconomics. However, packaging, formulation, or excipients are unique characteristics of each drug. In that way, switching from adalimumab originator to biosimilar and between biosimilars could have implications in the clinical practice. The objective of this study is to describe our clinical experience in switching from adalimumab originator to biosimilar and switching back again. A single-center retrospective cohort study was conducted that included seventeen patients with HS treated with adalimumab originator in the maintenance phase, and that achieved Hidradenitis Suppurativa Clinical Response (HiSCR), who were switched to adalimumab biosimilar for no medical reasons. The reason for the change was to improve pharmacoeconomic efficiency, following our hospital policies on biologics. Median duration with adalimumab originator treatment before switching was 48 weeks. After switching, 41.2% of patients maintained HiSCR response without additional issues, while 58.8% (10/17) reported problems after the change. Switching from adalimumab originator to biosimilar in well-controlled patients could imply problems in efficacy and adherence. HDAC inhibitor Switching back to adalimumab originator appears to solve most of the problems, but some patients can lose confidence in the drug and discontinue it. It would be worthwhile to evaluate the benefit-risk ratio individually when switching an HS patient to adalimumab biosimilar.Individual curves for tumor growth can be expressed as mathematical models. Herein we exploited a pharmacokinetic-pharmacodynamic (PKPD) model to accurately predict the lung growth curves when using data from a clinical study. Our analysis included 19 patients with non-small cell lung cancer treated with specific hypofractionated regimens, defined as stereotactic body radiation therapy (SBRT). The results exhibited the utility of the PKPD model for testing growth hypotheses of the lung tumor against clinical data. The model fitted the observed progression behavior of the lung tumors expressed by measuring the tumor volume of the patients before and after treatment from CT screening. The changes in dynamics were best captured by the parameter identified as the patients' response to treatment. Median follow-up times for the tumor volume after SBRT were 126 days. These results have proven the use of mathematical modeling in preclinical anticancer investigations as a potential prognostic tool.Introduction and objective Assessing the abuse potential of new substances with central nervous system activity is essential for preventing possible risks of misuse and addiction. The same methodology is recommended for the evaluation of the abuse potential of recreational drugs. This systematic review aims to assess the pharmacological effects related to the abuse potential and pharmacokinetics of cathinones, which are evaluated in both experimental and prospective observational studies in humans. Materials and Methods A systematic search of the published literature was conducted to retrieve studies that had administered cathinone, mephedrone, methylone, and diethylpropion to evaluate their acute pharmacological effects related to abuse potential. Results The search yielded 583 results, 18 of which were included to assess the abuse potential of cathinone (n = 5), mephedrone (n = 7), methylone (n = 1), and diethylpropion (n = 5). All four substances induce stimulant and euphorigenic effects that resemble those of amphetamines and MDMA, and their different intensities may be associated with varying levels of abuse potential. Conclusions Cathinone, mephedrone, methylone, and diethylpropion induce a range of desirable and reinforcing effects that may, to some extent, result in abuse potential. Further investigation is needed to minimize and prevent their impact on society and public health.Giant cell arteritis (GCA) is a systemic vasculitis with a direct and indirect increased risk of acute and chronic vascular events, affecting large and medium vessels, and responsible for most of the morbidity and mortality of this disease. We aimed in this review to provide an updated synthesis of knowledge regarding cardiovascular events observed in GCA. By definition, GCA patients are over 50 and often over 70 years old, and subsequently also present age-related cardiovascular risk factors. In addition, the systemic and vascular inflammation as well as glucocorticoids (GC) probably contribute to an accelerated atherosclerosis and to vascular changes leading to arterial stenoses and aortic dilations and/or dissections. GCA-related ischemic complications, especially ophthalmologic events, stroke or myocardial infarcts are mostly observed within the first months after the diagnosis, being mainly linked to the vasculitic process. Conversely, aortic complications, including dilations or dissections, generally occur several months or years after the diagnosis, mainly in patients with large-vessel vasculitis. In these patients, other factors such as atherosclerosis, GC-related endothelial damage and vascular wall remodeling/healing probably contribute to the vascular events. GCA management includes the detection and treatment of these previous and newly induced cardiovascular risk factors. Hence, the use of cardiovascular treatments (e.g., aspirin, anticoagulation, statins, anti-hypertensive treatments) should be evaluated individually. Aortic structural changes require regular morphologic evaluations, especially in patients with previous aortitis. The initial or secondary addition of immunosuppressants, especially tocilizumab, an anti-IL-6 receptor antibody, is discussed in patients with GCA-related cardiovascular complications and, more consensually, to limit GC-mediated comorbidities.Although larger trinucleotide expansions give rise to a neurodevelopmental disorder called fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by a "premutation" (55-200 CGG repeats) in the FMR1 gene. FXTAS is one of the more common single-gene forms of late-onset ataxia and tremor that may have a more complex development in women, with atypical presentations. After a brief presentation of the atypical case of an Italian woman with FXTAS, who had several paroxysmal episodes suggestive of acute cerebellar and/or brainstem dysfunction, this article will revise the phenotype of FXTAS in women. Especially in females, FXTAS has a broad spectrum of symptoms, ranging from relatively severe diseases in mid-adulthood to mild cases beginning in later life. Female FXTAS and male FXTAS have a different symptomatic spectrum, and studies on the fragile X premutation should be conducted separately on women or men. Hopefully, a better understanding of the molecular processes involved in the polymorphic features of FXTAS will lead to more specific and effective therapies for this complex disorder.The aim of this study was to evaluate the effectiveness of smear layer removal after the use of different irrigation methods (passive ultrasonic irrigation (PUI), continuous ultrasonic irrigation (CUI), apical negative pressure irrigation and conventional irrigation) using scanning electron microscopy (SEM) as an analytical tool. A total of 100 single-canal teeth were decoronated and randomly divided into five groups (n = 20) according to the irrigation method used conventional irrigation with front outlet syringe, conventional irrigation with lateral outlet syringe, apical negative pressure irrigation (EndoVac), PUI with Irrisafe and CUI with ProUltra PiezoFlow ultrasonic irrigation needle. Root canal preparation was performed with the ProTaper Gold system up to the F4 instrument, and 5.25% NaOCl was used as an irrigant. After chemical-mechanical preparation, the roots were split longitudinally, and the coronal, middle and apical thirds were examined. SEM digital photomicrographs were taken at ×1000 magnification to evaluate the amount of smear layer in each root canal third; CUI significantly removed more smear layer than any other irrigant activation protocol (p less then 0.