Purinergic regulation of pulmonary vascular tone.

Purinergic signaling is a crucial determinant in the regulation of pulmonary vascular physiology and presents a promising avenue for addressing lung diseases. This intricate signaling system encompasses two primary receptor classes: P1 and P2 receptors. P1 receptors selectively bind adenosine, while P2 receptors exhibit an affinity for ATP, ADP, UTP, and UDP. Functionally, P1 receptors are associated with vasodilation, while P2 receptors mediate vasoconstriction, particularly in basally relaxed vessels, through modulation of intracellular Ca2+ levels. The P2X subtype receptors facilitate extracellular Ca2+ influx, while the P2Y subtype receptors are linked to endoplasmic reticulum Ca2+ release. Notably, the primary receptor responsible for ATP-induced vasoconstriction is P2X1, with α,ß-meATP and UDP being identified as potent vasoconstrictor agonists. Interestingly, ATP has been shown to induce endothelium-dependent vasodilation in pre-constricted vessels, associated with nitric oxide (NO) release. In the context of P1 receptors, adenosine stimulation of pulmonary vessels has been unequivocally demonstrated to induce vasodilation, with a clear dependency on the A2B receptor, as evidenced in studies involving guinea pigs and rats. Importantly, evidence strongly suggests that this vasodilation occurs independently of endothelium-mediated mechanisms. Furthermore, studies have revealed variations in the expression of purinergic receptors across different vessel sizes, with reports indicating notably higher expression of P2Y1, P2Y2, and P2Y4 receptors in small pulmonary arteries. While the existing evidence in this area is still emerging, it underscores the urgent need for a comprehensive examination of the specific characteristics of purinergic signaling in the regulation of pulmonary vascular tone, particularly focusing on the disparities observed across different intrapulmonary vessel sizes. Consequently, this review aims to meticulously explore the current evidence regarding the role of purinergic signaling in pulmonary vascular tone regulation, with a specific emphasis on the variations observed in intrapulmonary vessel sizes. This endeavor is critical, as purinergic signaling holds substantial promise in the modulation of vascular tone and in the proactive prevention and treatment of pulmonary vascular diseases.

Brazilian indigenous nonstarter lactic acid bacteria enhance the diversification of volatile compounds in short-aged cheese.

There is growing interest in using autochthonous lactic acid bacteria (LAB) that provide unique sensory characteristics to dairy products without affecting their safety and quality. This work studied the capacity of three Brazilian indigenous nonstarter LABs (NSLAB) to produce biogenic amines (BAs) and evaluated their effect on the volatile organic compounds (VOCs), microbial LAB communities, and physicochemical profile of short-aged cheese. Initially, the strain's potential for biosynthesis of BAs was assessed by PCR and in vitro assays. Then, a pilot-scale cheese was produced, including the NSLAB, and the microbial and VOC profiles were analyzed after 25 and 45 days of ripening. As a results, the strains did not present genes related to relevant BAs and did not produce them in vitro. During cheese ripening, the Lactococci counts were reduced, probably in the production of alcohols and acid compounds by the NSLAB. Each strain produces a unique VOC profile that changes over the ripening time without the main VOCs related to rancid or old cheese. Particularly, the use of the strain Lacticaseibacillus. paracasei ItalPN16 resulted in production of ester compounds with fruity notes. Thus, indigenous NSLAB could be a valuable tool for the enhancement and diversification of flavor in short-aged cheese.

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.

Effect of positive end-expiratory pressure on lung injury and haemodynamics during experimental acute respiratory distress syndrome treated with extracorporeal membrane oxygenation and near-apnoeic ventilation.

BACKGROUND: Lung rest has been recommended during extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). Whether positive end-expiratory pressure (PEEP) confers lung protection during ECMO for severe ARDS is unclear. We compared the effects of three different PEEP levels whilst applying near-apnoeic ventilation in a model of severe ARDS treated with ECMO. METHODS: Acute respiratory distress syndrome was induced in anaesthetised adult male pigs by repeated saline lavage and injurious ventilation for 1.5 h. After ECMO was commenced, the pigs received standardised near-apnoeic ventilation for 24 h to maintain similar driving pressures and were randomly assigned to PEEP of 0, 10, or 20 cm H2O (n=7 per group). Respiratory and haemodynamic data were collected throughout the study. Histological injury was assessed by a pathologist masked to PEEP allocation. Lung oedema was estimated by wet-to-dry-weight ratio. RESULTS: All pigs developed severe ARDS. Oxygenation on ECMO improved with PEEP of 10 or 20 cm H2O, but did not in pigs allocated to PEEP of 0 cm H2O. Haemodynamic collapse refractory to norepinephrine (n=4) and early death (n=3) occurred after PEEP 20 cm H2O. The severity of lung injury was lowest after PEEP of 10 cm H2O in both dependent and non-dependent lung regions, compared with PEEP of 0 or 20 cm H2O. A higher wet-to-dry-weight ratio, indicating worse lung injury, was observed with PEEP of 0 cm H2O. Histological assessment suggested that lung injury was minimised with PEEP of 10 cm H2O. CONCLUSIONS: During near-apnoeic ventilation and ECMO in experimental severe ARDS, 10 cm H2O PEEP minimised lung injury and improved gas exchange without compromising haemodynamic stability.

Lexical Relations in Spanish-Speaking Older Adults.

This study analyzed the types of lexical relations produced by Spanish-speaking older adults with typical aging. A total of 120 older adults completed a word association norms task with 117 stimulus words, which allowed us to explore differences in associations by sex, age, and years of education. We employed two classifications to code the lexical relations: a traditional classification (paradigmatic versus syntagmatic) and a second classification categorizing responses into 17 types of associations (e.g., categorial versus non-categorial). Our results show that participants have a preference for paradigmatic responses (e.g., dog-animal), as well as associations with thematic-contextual co-occurrence plus semantic relations (e.g., cradle-baby). These findings suggest that older adults tend to establish lexical relations based on a combined link, one that is semantic and contextual.

Silent Destruction: Fulminant Hepatitis and the Hidden Danger of Weight Loss Drugs.

INTRODUCTION: The use of natural products for therapeutic purposes is a common practice throughout the world, in part, due to the global obesity epidemic and the search for products with appetite suppression and weight loss properties, which include nutritional supplements, vitamins and minerals to herbal products. It is known that such products may be associated with various adverse health effects. Thus, the objective of this study is to report a series of cases of patients, who presented fulminant liver failure (HFI) requiring liver transplantation (LT), related to the consumption of products used for weight loss. MATERIAL AND METHODS: This is a retrospective cohort based on the evaluation of patients listed for LT due to IHF at the Hospital das Clínicas of the Universidade Estadual de Campinas, between 1991 and 2022, with patients who had confirmed consumption of products with the aim of loss being selected. RESULTS: During the studied period, 92 patients were listed for HT due to IHF according to the Kings College criteria, with 5 cases being selected with proven consumption of herbal products for weight loss, and other causes that could explain the IHF were excluded. Four (80%) of the patients were female, with a mean age of 40.5 years, and 40% of the cases died. DISCUSSION AND CONCLUSIONS: Unlike traditional pharmaceutical medicines, in most countries, the commercialization of these products is not conditioned on clinical and safety evidence or prior approval by regulatory bodies. Hepatoxicity can be related to several factors, such as the presence of toxins naturally found in plants, the presence of heavy metals, contamination during obtaining or processing and the addition of substances omitted from the labels. The use of weight loss products can evolve with IHF, a fact that deserves attention, due to ease of access and growing demand, and it is important to regulate the trade of these products and raise public awareness about the risks of use without professional supervision and guidance.

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.

Identifying markers volatiles in Brazilian virgin oil by multiple headspace solid-phase microextraction, and chemometrics tools.

A protocol was optimized to determine the volatile profile from monovarietal virgin olive oil (VOO) by multiple headspace solid-phase microextraction (MHS-SPME) followed by gas chromatography-mass spectrometry (GC-MS) analysis. For this, a Plackett-Burman (PB) and central composite rotational designs (CCRD) were used to define the best condition of extraction. Moreover, fatty acids profile and principal component analysis (PCA) was used to identify markers among the cultivars. The amount of 0.1 g of sample was enough to express the volatile composition of the olive oils by MHS-SPME. Volatile compounds [nonanal, (Z)-3-Hexen-1-ol, (Z)-3-Hexenyl Acetate, Hexyl Acetate, 3-Methylbutyl Acetate, (E)-2-Hexen-1-ol, (E)-2-Hexenyl Acetate] and fatty acids [C17:1, C18, C18:1, C18:2] were those reported such as the markers in the varieties of olive oils. The PCA analysis allowed the classification of the most representative volatiles and fatty acids for each cultivar. Through two principal components was possible to obtain 81.9% of explanation of the variance of the compounds. The compounds were quantified using a validated method. The MHS-SPME combined with multivariate analysis showed a promising tool to identify markers and for the discrimination of olive oil varieties.

Clinical validation of the nursing diagnostic proposition perioperative thirst. / Validación clínica de la propuesta diagnóstica de enfermería de sed perioperatoria.

OBJECTIVE: to verify the clinical validity of the proposition of a new nursing diagnosis called perioperative thirst, based on the diagnostic accuracy of its clinical indicators, including the magnitude of effect of its etiological factors. METHOD: clinical diagnostic validation study with a total of 150 surgical patients at a university hospital. Sociodemographic variables and clinical indicators related to thirst were collected. The latent class analysis technique was used. RESULTS: two models of latent classes were proposed for the defining characteristics. The model adjusted preoperatively included: dry lips, thick saliva, thick tongue, desire to drink water, caregiver report, dry throat and constant swallowing of saliva. In the postoperative period: dry throat, thick saliva, thick tongue, constant swallowing of saliva, desire to drink water, bad taste in the mouth. The factors related to "high ambient temperature" and "dry mouth" are associated with the presence of thirst, as well as the associated conditions "use of anticholinergics" and "intubation". The prevalence of thirst was 62.6% in the pre and 50.2% in the immediate postoperative period. CONCLUSION: the diagnostic proposition of perioperative thirst showed good accuracy parameters for its clinical indicators and etiological effects. This proposition in a nursing taxonomy will allow greater visibility, appreciation and treatment of this symptom.(1) Evaluates the accuracy of the proposition of the nursing diagnosis perioperative thirst; (2) Allows refined diagnosis for use in clinical practice, teaching and research; (3) Strengthens the systematization of perioperative nursing care; (4) Highlights thirst management as part of care, considering its high prevalence and discomfort; (5) Presents a structure with good accuracy parameters which are representative of thirst.

Implementation of the thirst management model in the burn unit guided by knowledge translation.

OBJECTIVE: To implement the preoperative Thirst Management Model, measuring its adoption, coverage, acceptability, feasibility and fidelity by nursing in a burn unit. METHOD: Quasi-experimental, pre- and post-test intervention study. Sample of 59 patients at pre-implementation and 40 post-implementation and 36 nursing professionals participating in the implementation in a burn unit from August (2019) to March (2020). Statistical analysis used Mann-Whitney and Chi-square. RESULTS: Adoption of management ranged from 0.0% to 72.5% post-implementation. The capacity coverage was 87.5% of nurses and 87.9% of nursing technicians. There was acceptability and feasibility of thirst management by professionals. In the plan-do-study-act cycles, three pillars of the Model reached the goals, showing fidelity. CONCLUSION: The implantation of the Preoperative Thirst Management Model had acceptability and feasibility by the nursing team, showing fidelity in achieving the proposed goals, in addition to the adoption of evidence in clinical practice after high coverage professional training.

Complementary Therapies and Their Association with Problems in Therapeutic Adherence to Conventional Synthetic DMARDs in Rheumatoid Arthritis: A Cross-Sectional Study.

The use of complementary therapies is highly prevalent among patients with rheumatoid arthritis (RA). Nevertheless, the use of complementary medicine could involve problems in the following of scientifically accepted treatments. To date, there is limited information regarding the association of nonconventional therapies with problems regarding compliance with the treatment. Therefore, the objective of this study was to identify whether the utilization of complementary therapies is associated with a high risk of problems regarding therapeutic adherence to conventional synthetic disease-modifying anti-rheumatic drugs (cs-DMARDs) in RA patients. A survey was performed with RA patients in an outpatient rheumatology clinic in a university hospital; the use of complementary therapies, as well as their type, was identified. To assess problems with therapeutic adherence, we used the four-item Morisky-Green scale. A comprehensive assessment of clinical and therapeutic characteristics was performed. Univariable and multivariable models were performed to identify the risk of problems with therapeutic adherence in users of complementary therapies. In total, 250 RA patients were included; 92% used complementary therapies. Of them, the most frequently used were herbal medicine (65%), homeopathy (64%), and cannabis and its derivatives (51%). In the univariable logistic regression analysis, the factors associated with problems in the therapeutic adherence to cs-DMARDs were age (p = 0.019), the presence of other comorbidities (p = 0.047), and the use of complementary therapies (p = 0.042). After controlling for potential confounders, the use of complementary therapies increased the risk of problems with therapeutic adherence to cs-DMARDs (adjusted OR = 2.84, 95% CI = 1.06-7.63, p = 0.037). We concluded that the use of complementary therapies increases the risk of problems with therapeutic adherence. Therefore, for physicians and healthcare professionals, the early identification of the use of nonconventional therapies in their RA patients is required, followed by a directed discussion with their patients about the risks and benefits to which they could be exposed to complementary therapies.

Effects of carbohydrate use on preoperative thirst: a randomized clinical trial.

OBJECTIVES: to evaluate the effectiveness of carbohydrate popsicles, carbohydrate solution, and usual care (fasting) on the intensity and discomfort of preoperative thirst. METHODS: a randomized clinical trial with 60 preoperative patients aged between 18 and 60 years, randomized into three groups: control (fasting), carbohydrate solution (100 ml), and carbohydrate popsicle (100 ml). The outcomes were thirst intensity and discomfort. RESULTS: there was a difference between groups for final thirst intensity (p = 0.01) and final thirst discomfort (p = 0.001). The effect size for both the Solution Group and the Popsicle Group was robust: 0.99 and 1.14, respectively. CONCLUSIONS: the groups that received the carbohydrate fasting abbreviation showed a reduction in thirst discomfort compared to the control group. The carbohydrate popsicle proved more effective in reducing the intensity of thirst. NCT: 3.209.283.

Cupuassu from bean to bar: Sensory and hedonic characterization of a chocolate-like product.

The processing of cupuassu (Theobroma grandiflorum Schum) beans after fermentation gives a chocolate-like product, the cupulate. The high amount of pulp adhered to the seeds hinders the fermentation. Consequently, it is necessary to depulp the seeds to perform the process, even though the pulp contains important substrates for the formation of flavor precursors. To verify whether the complete or partial removal of the pulp influences the sensory characteristics of the product, fermentation was performed with three pulp concentrations (0, 7.5, and 15%) and two schemes of turning for aeration of the mass: fixed (R1) and according to the temperature (R2), in a total of six experiments (0R1, 0R2, 7.5R1, 7.5R2, 15R1 and 15R2). The beans were processed to obtain cupulates, which were submitted to tests performed with consumers, to express their preference and attributes (acceptance, purchase intent, Check All That Apply - CATA), and then to tests with a trained panel, the Quantitative Descriptive Profile (QDP) to characterize the samples. Both tests showed the consumers' perceptions that the cupulates have peculiar sensory characteristics. In the Consumer Test, through the Preference Mapping, all the samples of cupulates obtained from R1 conditions were preferred. In the penalty analysis, these same samples showed positive attributes that mask the negative attributes. Both CATA and QDP results showed that cupulate samples produced from seeds with a higher amount of pulp (15R1 and 15R2) had a higher number of positive mentions, for their fruity and floral flavors. The research also demonstrated that all samples gave the perception of an earthy taste, an important reason for consumer rejection, as well as a bad residual flavor. Thus, the results showed that the presence of the pulp in the fermentation environmental is important to the formation of flavor compounds and improving the sensory acceptance of the products.

Pigmented eccrine poroma in an atypical location.

Eccrine poroma is the term that includes benign neoplasms of the terminal duct of the eccrine sweat glands, which may clinically and dermoscopically resemble other melanoma and non-melanoma skin tumors. They are often located on the extremities (especially palms and soles), presenting as normochromic or erythematous papules and nodules, measuring up to 2 cm. Pigmented variants are uncommon, accounting for less than 20% of cases. This report describes a 37-year-old man who developed a large pigmented eccrine poroma on his right shoulder, causing diagnostic difficulty. Histopathological examination revealed a nodular neoplasm consisting of small, monomorphic, cuboidal cells, with ample, eosinophilic cytoplasm and well-defined borders, in addition to conspicuous intercellular bridges, with melanin deposits diffusely distributed inside them. The absence of cytological atypia, cellular pleomorphism, increased mitotic activity, and necrosis foci corroborated the diagnostic exclusion of porocarcinoma, which can develop from eccrine poroma.

ANCA-associated vasculitis following Oxford-AstraZeneca COVID-19 vaccine in Brazil: Is there a causal relationship? A case report.

This article presents a case of rapidly progressive glomerulonephritis following the Oxford-AstraZeneca COVID-19 vaccine in a female patient 58 years old. After 5 days, she presented fatigue, paleness, arthralgia on hands, knees, ankles, foamy urine, and elevated blood pressure. Exams showed serum creatinine of 2.2 mg/dL (baseline creatinine of 1.0 mg/dL). Urinalysis revealed hematuria, and her 24-h urinary protein excretion was 4.4 g. Additional exams showed hypercholesterolemia, severe anemia, and normal serum albumin. Testing of antineutrophil cytoplasmic antibodies anti-myeloperoxidase was positive at a titer of 1/80. Serum and urine protein electrophoresis and other exams showed no alterations. She was started on steroid pulse therapy after worsening kidney function, reaching serum creatinine of 3.3 mg/dL. A kidney biopsy revealed crescentic glomerulonephritis with glomerular sclerosis, fibrous crescents, interstitial fibrosis, and tubular atrophy. Induction therapy was given with intravenous cyclophosphamide 0.5 g/m2 for 6-monthly pulses, followed by maintenance therapy with oral azathioprine at 2 mg/kg and prednisone tapering. The patient did not develop any complications during the induction therapy, and is currently on maintenance therapy with a serum creatinine of 1.87 mg/dL.

Validation of New York/California Score in the Preoperative Period of Liver Transplant for Hepatocellular Carcinoma at University of Campinas's Hospital.

Liver transplant is the main treatment for hepatocellular carcinoma and there is currently an important demand from patients waiting in transplant queues. Thus, it is extremely important to improve the criteria for selecting patients who will undergo transplant to mitigate graft loss and reduce cases of recurrence. Thus, it becomes necessary to use models, such as the New York/California (NYCA), that include alpha fetoprotein as a marker of recurrence and prognosis. The aim of this study was to assess whether the NYCA score correlated with the presence of tumor recurrence after transplant in patients undergoing orthotopic liver transplant at the Clinics Hospital of the University of Campinas. We had 214 patients undergoing liver transplant who met the inclusion Milan criteria. The age of the patients ranged from 34 to 77 years, with a median age of 61 years. The mean waiting time on the transplant list was 6.12 months. After calculating the NYCA score, it was possible to stratify 13 patients (6.1%) as high risk, 64 patients (29.9%) as medium risk, and 137 patients (64%) as low risk. Patients with recurrence had higher scores with a mean of 4 points in relapse and 2 points in the absence of relapse (P = .0011). Patients with recurrence had statistically higher high- and medium-risk scores (P = .0010). Therefore, the NYCA score was higher in patients with recurrence. Therefore, in this study, our findings suggest the possibility of using the NYCA score as an aid to detect patients with a higher risk of tumor recurrence.

Refinement of the Milan Criteria: Role of α-Fetoprotein In Liver Transplantation for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary neoplasm of the liver, mainly secondary to cirrhosis caused by hepatitis C virus. Liver transplant (LT) is considered the best treatment because, in addition to removing the tumor, it also removes the underlying cirrhotic liver. The Milan criteria for LT have limitations because they do not consider the biological characteristics of the tumor. Thus, our objective was to evaluate the association of α-fetoprotein (AFP) levels before LT performed for HCC with recurrence of this tumor, and, based on the results, a new predictive model that combines the AFP values at the list entry with the usual criteria of tumor size and number of nodules was validated. In present study, the Score AFP model, we were able to correlate a greater occurrence of relapse with scores of 3 and 4 (P = .0001), indicating the usefulness of using AFP as a predictor of recurrence.

Validation of Metroticket Score in the Preoperative Period of Liver Transplantation for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the sixth leading cause of cancer in the world, and liver transplant (LT) is a good therapeutic option in selected cases because it treats the neoplasm and the underlying disease. Recurrence after LT is usually aggressive and has low survival; thus, an adequate selection of recipients is ideal. The new models aim to assess the individual risk of HCC recurrence in patients undergoing LT and to improve post-LT survival. In this study, our aim was to assess the applicability of the "Metroticket" score, correlating it with our rates of recurrence and survival after LT. Overall survival at 5 years in our study differed from that in Metroticket 2.0 because that study did not consider only recurrence as the cause of death; our study evaluated only patients with recurrence, so we were able to validate the score as a predictor of greater tumor aggressiveness after LT.

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.