Nitrofurantoin as an Add-On to Conventional Prophylaxis for the Treatment of Urinary Tract Infections in Kidney Recipients: A Prospective Cohort Study.

Urinary tract infections (UTIs) constitute one of the main complications in kidney recipients, increasing both morbidity and mortality. Due to the resurgence of antimicrobial resistance, new prophylactic approaches are being investigated. Nitrofurantoin is an antibiotic from the nitrofuran group that is effective against several Gram-negative and Gram-positive organisms; hence, there has been a resurgence in its prescription for treating MDR pathogens. Objectives: This study aims to assess the effectiveness of nitrofurantoin as an add-on to conventional therapy (amikacin + ceftriaxone or cefotaxime) for the treatment of urinary tract infections in kidney recipients. Methods: In a prospective cohort study, we included patients who received a kidney in a tertiary-care hospital. According to the intensive care specialist, group 1 patients were treated with the conventional prophylactic treatment plus nitrofurantoin as an add-on. Group 2 patients were treated only with the conventional prophylactic treatment. They were followed-up for 3 months, and the incidence of urinary tract infections was reported. Results: The UTI incidence for group 1 at 3 months was 20.6%, and for group 2, it was 20.0%; no statistical difference between treatments was observed (p = 0.9). The most commonly isolated pathogens were E. coli (28.5) and K. pneumonie (28.5%). The factor most associated with developing a UTI was female gender (aHR: 7.0; 95% IC 2.3-20.9, p < 0.001). Conclusions: In our cohort study, nitrofurantoin as an add-on in conventional therapy did not prove to be effective in preventing UTI development; therefore, other treatment options should be considered as a part of prophylactic treatment.

Syndecan-1 Levels in Females with Active Rheumatoid Arthritis.

Background: The relationship between serum glycoprotein syndecan-1 and disease activity in rheumatoid arthritis (RA) is still unknown. This study aimed to evaluate whether serum syndecan-1 concentrations are associated with moderate/severe disease activity. Methods: Study Design: This was a cross-sectional study. Seventy-five adult women with RA were classified into (a) moderate/severe RA based on the disease activity score, using the erythrocyte sedimentation rate (DAS28-ESR ≥ 3.2, n = 50), and (b) RA in remission (DAS28-ESR < 2.6, n = 25). Twenty-five healthy women were taken as the reference group. Syndecan-1 levels were determined using enzyme-linked immunosorbent assay (ELISA). High values of serum syndecan-1 levels (≥24 ng/mL) were used to identify the utility values of this biomarker. Results: The patients with RA had higher levels of syndecan-1 than the controls (p < 0.001). RA patients with active disease had higher syndecan-1 levels than RA patients in remission (57.6 vs. 23.5 ng/mL, respectively; p = 0.002). High syndecan-1 concentrations demonstrated the following utility values for identifying disease activity: sensitivity, 84% (95%CI: 71-93); specificity, 52% (95%CI: 31-72); positive predictive value, 78% (95%CI: 70-84); and negative predictive value, 62% (95%CI: 44-77). Conclusions: High syndecan-1 levels have good sensitivity and positive predictive value for identifying disease activity; however, their specificity is limited. Future prospective studies are needed to assess whether syndecan-1 levels can predict treatment failure in RA.

Role of Myostatin in Rheumatoid Arthritis: A Review of the Clinical Impact.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects synovial joints and that frequently involves extra-articular organs. A multiplicity of interleukins (IL) participates in the pathogenesis of RA, including IL-6, IL-1ß, transforming growth factor-beta (TGF-ß), and tumor necrosis factor (TNF)-α; immune cells such as monocytes, T and B lymphocytes, and macrophages; and auto-antibodies, mainly rheumatoid factor and anti-citrullinated protein antibodies (ACPAs). Skeletal muscle is also involved in RA, with many patients developing muscle wasting and sarcopenia. Several mechanisms are involved in the myopenia observed in RA, and one of them includes the effects of some interleukins and myokines on myocytes. Myostatin is a myokine member of the TGF-ß superfamily; the overproduction of myostatin acts as a negative regulator of growth and differentiates the muscle fibers, limiting their number and size. Recent studies have identified abnormalities in the serum myostatin levels of RA patients, and these have been found to be associated with muscle wasting and other manifestations of severe RA. This review analyzes recent information regarding the relationship between myostatin levels and clinical manifestations of RA and the relevance of myostatin as a therapeutic target for future research.

Risk Factors Associated with Adverse Events Leading to Methotrexate Withdrawal in Elderly Rheumatoid Arthritis Patients: A Retrospective Cohort Study.

Background: Rheumatoid arthritis (RA) in elderly population represents a challenge for physicians in terms of therapeutic management. Methotrexate (MTX) is the first-line treatment among conventional synthetic-disease-modifying anti-rheumatic drugs (cs-DMARDs); however, it is often associated with adverse events (AEs). Therefore, the objective of this study was to identify the incidence and risk factors of MTX discontinuation due to AEs in elderly patients with RA in a long-term retrospective cohort study. Methods: Clinical sheets from elderly RA patients taking MTX from an outpatient rheumatology consult in a university centre were reviewed. To assess MTX persistence, we used Kaplan-Meir curves and Cox regression models to identify the risk of withdrawing MTX due to adverse events. Results: In total, 198 elderly RA patients who reported using MTX were included. Of them, the rates of definitive suspension of MTX due to AEs were 23.0% at 5 years, 35.6% at 10 years and 51.7% at 15 years. The main organs and system involved were gastrointestinal (15.7%) and mucocutaneous (3.0%). Factors associated with withdrawing MTX due to AEs were MTX dose ≥ 15 mg/wk (adjusted HR: 2.46, 95% CI: 1.22-4.96, p = 0.012); instead, the folic acid supplementation was protective for withdrawal (adjusted HR: 0.28, 95% CI: 0.16-0.49, p < 0.001). Conclusions: Higher doses of MTX increase the risk of withdrawals in elderly RA, while folic acid supplementation reduces the risk. Therefore, physicians working in therapeutic management for elderly patients using MTX must focus on using lower MTX doses together with the concomitant prescription of folic acid.

Intravenous Vitamin C as an Add-on Therapy for the Treatment of Sepsis in an Intensive Care Unit: A Prospective Cohort Study.

Background and Objectives: According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection". The increased presence of free radicals causes an increase in oxidative stress. Vitamin C is an essential water-soluble vitamin with antioxidant activity and immunoregulatory effects that plays a potential role in the treatment of bacterial infections. Our aim was to evaluate the effectiveness of adding vitamin C to the conventional treatment of sepsis to decrease its mortality rate. Materials and Methods: In a prospective cohort study, we included patients with a diagnosis of sepsis and a SOFA score ≥ 9 who were evaluated in an Intensive Care Unit at a secondary-care hospital. According to the intensive care specialist, they were treated using two different strategies: Group 1-patients with sepsis treated with conventional treatment without vitamin C; Group 2-patients with sepsis with the addition of vitamin C to conventional treatment. Results: We included 34 patients with sepsis. The incidence of mortality was 38%, and 47% of patients used vitamin C as an adjuvant to the basic treatment of sepsis. In the basal analyses, patients treated with use of vitamin C compared to patients treated without vitamin C required less use of glucocorticoids (75% vs. 100%, p = 0.039). At follow-up, patients treated without vitamin C had higher mortality than patients treated with vitamin C as an adjuvant for the treatment of sepsis (55.6% vs. 18.8%, p = 0.03). We observed that the use of vitamin C was a protective factor for mortality in patients with sepsis (RR: 0.54, 95% CI: 0.31-0.96, p = 0.03). Conclusions: The use of vitamin C as an adjuvant to treatment decreases the risk of mortality by 46% in patients with sepsis and SOFA ≥ 9 compared to patients treated without vitamin C as an adjuvant to sepsis.

Myostatin Levels and the Risk of Myopenia and Rheumatoid Cachexia in Women with Rheumatoid Arthritis.

Background: Myostatin is a regulator of muscle size. To date, there have been no published studies focusing on the relation between myostin levels and myopenia in rheumatoid arthritis (RA). Objective: Evaluate the value of serum myostatin as a biomarker of cachexia and low skeletal muscle mass (LSMM) in RA patients, along with whether high serum myostatin is associated to these conditions after adjusting for potential confounders. Methods: This cross-sectional study included 161 female RA patients and 72 female controls. In the RA group, we assessed several potential risk factors for LSMM and rheumatoid cachexia. Dual-energy X-ray absorptiometry was used to quantify the skeletal muscle mass index (SMMI) (considering LSMM ≤ 5.5 kg/m2) and the presence of rheumatoid cachexia (a fat-free mass index ≤ 10 percentile and fat mass index ≥ 25 percentile of the reference population). Serum myostatin concentrations were determined by ELISA. To identify a cut-off for high serum myostatin levels, we performed ROC curve analysis. Multivariable logistic regression analysis was used to identify the risk factors for LSMM and rheumatoid cachexia. The risk was expressed as odds ratios (ORs) and their 95% confidence intervals (95% CIs). Results: Compared to the controls, the RA group had a higher proportion of LSMM and exhibited high serum myostatin levels (p < 0.001). ROC curve analysis showed that a myostatin level ≥ 17 ng/mL was the most efficient cut-off for identifying rheumatoid cachexia (sensitivity: 53%, specificity: 71%) and LSMM (sensitivity: 43%, specificity: 77%). In the multivariable logistic regression, RA with high myostatin levels (≥17 ng/mL) was found to increase the risk of cachexia (OR = 2.79, 95% CI: 1.24-6.29; p = 0.01) and LSMM (OR = 3.04, 95% CI: 1.17-7.89; p = 0.02). Conclusions: High serum myostatin levels increase the risk of LSMM and rheumatoid cachexia. We propose that high myostatin levels are useful biomarkers for the identification of patients in risk of rheumatoid cachexia and myopenia.

Serum chemerin levels: A potential biomarker of joint inflammation in women with rheumatoid arthritis.

BACKGROUND: Chemerin has a potential role in perpetuating inflammation in autoimmune diseases. Nevertheless, to date, there is no conclusive information on whether high chemerin levels increase the severity of rheumatoid arthritis (RA). Therefore, this study evaluated whether serum chemerin is a biomarker of disease activity in RA patients. METHODS: Study design: cross-sectional. The assessment included clinical and laboratory characteristics, body mass index (BMI) and fat mass. The severity of the disease activity was identified according to the DAS28-CRP index as follows: A) RA with a DAS28-CRP≤2.9 (remission/mild activity) and B) RA with a DAS28-CRP>2.9 (moderate/severe activity). Serum chemerin concentrations were measured by ELISA, and ≥103 ng/mL was considered a high level. Logistic regression analysis was applied to determine whether high chemerin levels were associated with disease activity in RA after adjusting for confounders. Multiple regression analysis was performed to identify variables associated with chemerin levels. RESULTS: Of 210 RA patients, 89 (42%) subjects had moderate/severe disease activity and had higher serum chemerin levels than patients with low disease activity or remission (86 ± 34 vs 73± 27; p = 0.003). Serum chemerin correlated with the number of swollen joints (r = 0.15; p = 0.03), DAS28-CRP (r = 0.22; p = 0.002), and C-reactive protein levels (r = 0.14; p = 0.04), but no correlation was observed with BMI and fat mass. In the adjusted logistic regression analysis, high chemerin levels (≥103 ng/mL) were associated with an increased risk of moderate/severe disease activity (OR: 2.76, 95% CI 1.35-5.62; p = 0.005). In the multiple regression analysis, after adjusting for potential confounders, serum chemerin levels were associated with higher DAS28-CRP (p = 0.002). CONCLUSIONS: Higher chemerin levels increased the risk of moderate and severe disease activity in RA. These results support the role of chemerin as a marker of inflammation in RA. Follow-up studies will identify if maintaining low chemerin levels can be used as a therapeutic target.

Utility of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as biomarker to predict therapeutic response to methotrexate in rheumatoid arthritis.

The objective of this study was to investigate the usefulness of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in predicting short-term therapeutic response to methotrexate (MTX) in rheumatoid arthritis (RA). Patients with active RA, with Disease Activity Score-28 joints (DAS-28) >3.2, starting oral MTX, were included. We measured at baseline, 3 and 6 mo: DAS-28, Health Assessment Questionnaire-Disability Index (HAQ-DI), patient's perception of disease severity, morning stiffness and pain, as well as modifications in sTREM-1 levels. A reduction in DAS-28 > 1.2 at 3 or 6 mo was considered adequate response. A significant decrease in DAS-28 was observed at 3 and 6 mo. HAQ-DI also decreased at 3 and 6 mo. No significant changes were observed in sTREM-1 levels at 3 or 6 mo. Using as cut-off a baseline value of sTREM-1 levels > 390 pg/ml, we obtained low values of sensitivity (61.5%), specificity (59.3%), positive predictive value (59.3%) and negative predictive value (61.5%) for adequate response to MTX at 3 mo. We found no clinical value of sTREM-1 levels in predicting therapeutic response to MTX in RA. Further studies should evaluate if sTREM-1 levels are predictive for other outcomes, including higher structural damage or good response to biologics.