An assessment on the effects of buffers on the productive, behavioral and metabolic parameters of Holstein dairy cows.

This study aimed to evaluate the impact of supplementing sodium bicarbonate or a commercial blend of buffering agents (BBA) comprising calcareous calcitic, magnesium oxide, calcareous algae, and sodium bicarbonate on the productive, behavioral and metabolic parameters of Holstein cows fed starchy diets. Over a 60-day trial period, thirty-six multiparous cows with an average milk yield of 38.84 ± 9.24 kg/day and 63.74 ± 18.63 days in milk (DIM), were randomly divided into two groups. The control group (n = 18) received a supplementation of 1.1% dry matter (DM) of sodium bicarbonate (Raudi®, Totalmix, Brazil), while the BBA group (n = 18) was administered with 0.5% DM of a blend of buffering agents (Equalizer®, Nutron/Cargill, Brazil). The mean values of ruminal pH (control 6.80 ± 0.06 and BBA 6.77 ± 0.06; P > 0.05) and volatile fatty acid (VFA) production (control: acetate 62.63 ± 1.29%, propionate 22.99 ± 1.07%, butyrate 14.30 ± 0.52%; BBA: acetate 63.07 ± 1.32%, propionate 23.47 ± 1.10%, butyrate 13.70 ± 0.57%), were similar (P > 0,05) between the two groups. The value of faecal pH was higher (P < 0.05) in the BBA group (6.25 ± 0.02) than the control group (6.12 ± 0.02). Animals treated with BBA exhibited lower (P < 0,05) dry matter intake (DMI) (24.75 ± 0.64 kg/day), higher feed efficiency (FE) (1.64 ± 0.03), and reduced feeding frequency (52.89 ± 3.73 n°/day) than the control group (DMI, 26.75 ± 0.62 kg/day; FE, 1.50 ± 0.03; feeding frequency, 66.07 ± 3.64 n°/day). Milk production remained similar across both groups (control, 39.11 ± 0.92 kg/day and BBA, 39.87 ± 0.92 kg/day; P > 0.05). Notably, the control group displayed a higher (P < 0,05) concentration of milk protein (1.21 ± 0.05 kg/day) than the BBA (1.18 ± 0.05 kg/day) group. The study concluded that both treatments effectively buffered the rumen and mitigated the risk of ruminal acidosis. Moreover, the higher faecal pH in the BBA-treated group suggests potential intestinal action attributable to the synergistic effects of diverse additives with buffering properties. Despite a reduced DMI, BBA-treated animals exhibited improved FE.

Temporal dominance of Sensations: Do different concepts of "dominance" affect the results?

The purpose of this study was to understand the role of "dominance" definitions in the results of TDS applied to consumers. This study compared two temporal dominance of sensations (TDS) approaches - TDS-I - that attracts the most attention and TDS-II - most intense/strongest sensation - in the context of evaluating artisanal Minas cheeses from the Serra da Canastra and chocolate with different cocoa concentrations samples. TDS curves were constructed and a trajectory-based principal component analysis (PCA) was performed dominance rates at ten equally spaced time points. Additionally, difference curves, multiple factor analysis (MFA) and regression vector coefficient (RV coefficient) were performed to compare the two approaches. The findings showed that the two approaches produced similar results, suggesting that consumers interpret the terms dominant and intense in a similar way during TDS evaluations, the results were even closer at the chocolate study than at the cheese study. However, in both approaches were observed low dominance rates and differences between the sensation perception time, mainly in the evaluation of cheese flavor. This variability may be attributed to the complexity of the cheese's flavor and the varied interpretations of dominance among evaluators. Despite these differences, the approaches showed similar characterizations across the same samples, demonstrating high reproducibility and a strong ability to differentiate between samples. This study demonstrates that the choice between the terms dominant (which captures more attention) or intense (stronger) to guide consumers in performing the sensory test does not significantly influence the results. Consequently, it is possible to adopt greater freedom and flexibility in the terminology used to instruct participants in conducting the test.

Fecal Proteolytic Bacteria and Staphylococcal Superantigens are Associated with Abdominal Pain Severity in Irritable Bowel Syndrome.

INTRODUCTION: Changes in the composition of the gut microbiota have been associated with the development of Irritable Bowel Syndrome (IBS). However, to what extent specific bacterial species relate to clinical symptoms remains poorly characterized. We investigated the clinical relevance of bacterial species linked with increased proteolytic activity, histamine production, and superantigen (SAg) production in IBS patients. METHODS: Fecal (n=309) and nasal (n=214) samples were collected from patients with IBS and healthy volunteers (HV). Clinical symptoms and gut transit time were evaluated. Bacterial abundance in feces and nasal swabs as well as fecal trypsin-like activity were assessed. RESULTS: The percentage of fecal samples containing Staphylococcus aureus was significantly higher in IBS compared to HV. Forty-nine % of S. aureus-positive fecal samples from patients with IBS were also positive for SAgs, compared to 12% of HV. Patients with IBS and positive fecal SAg-producing S. aureus reported higher pain scores than those without S. aureus. Moreover, increased fecal proteolytic activity was associated with abdominal pain. Fecal abundance of Paraprevotella clara and Alistipes putredinis was significantly decreased in IBS, particularly in samples with higher proteolytic activity. Patients with lower Alistipes putredinis or Faecalibacterium prausnitzii abundance reported more severe abdominal pain. DISCUSSION: In keeping with our preclinical findings, we show that increased presence of SAg-producing S. aureus in fecal samples of patients with IBS is associated with increased levels of abdominal pain. We also show that increased fecal proteolytic activity is associated with increased abdominal pain in patients with IBS.

Genetic divergence and truncation and simultaneous selection in inbred families (S1) of elephant grass for bioenergetic purposes via mixed models.

The State University of North Fluminense Darcy Ribeiro (UENF) has been developing for fifteen years a breeding program that aims at the development of new cultivars of elephant grass due to its high potential and the low availability of cultivars developed by genetic breeding programs that meet the needs of producers in the State of Rio de Janeiro. In this sense, inbred families were also obtained as a way of fixing potential alleles for traits related to production, as the inbreeding process apparently does not strongly affect elephant grass in aspects related to inbreeding depression. This study aimed to estimate genetic diversity, variance components and prediction of genotypic values in 11 (S1) elephant grass families, and perform the truncation and simultaneous selection of traits using the selection index, by mixed models. The experimental design consisted of randomized blocks with 11 (S1) families, three replications, and six plants per plot. For variables dry matter production, percentage of dry matter, plant height, stem diameter, number of tillers and leaf blade width, was performed the estimation of genetic parameters and selection of the best genotypes based selection index using mixed model. The descriptors were subjected to correlation analysis, distance matrices were generated by the Mahalanobis method, and individuals were grouped by the UPGMA method. In the selection via mixed models (REML/BLUP), families 6, 11, 8, 1, 3, 7, and 9 contributed most of the genotypes selected for the evaluated traits, indicating their high potential to generate superior genotype. The selection indices via mixed models indicated that the multiplicative index presented a greater selection gain.The phenotypic correlations showed the possibility of performing an indirect selection from six evaluated traits.The genotypes were separated into 18 groups by the Mahalanobis distance, allowing the observation of a wide genetic diversity. The most divergent and productive genotypes were self-fertilized to obtain the second generation (S2), continuing the development program.

Ibero-American Consensus for the Management of Peritoneal Sarcomatosis: Updated Review and Clinical Recommendations.

Peritoneal sarcomatosis is a rare malignant disease with a poor prognosis, secondary to peritoneal dissemination of abdominopelvic soft tissue sarcomas. Its rarity, together with the characteristic histological heterogeneity and the historically poor response to systemic treatments, has prevented the establishment of widely accepted treatment criteria with curative intent. In this sense, radical cytoreductive surgery (CRS) with peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (HIPEC), widely used in peritoneal carcinomatosis with excellent results, have not had the same evolutionary development in patients with peritoneal sarcomatosis. A multidisciplinary working group of experts in sarcomas and peritoneal oncological surgery established a series of recommendations based on current scientific evidence for the management of peritoneal sarcomatosis, taking into account the different histological subgroups of abdominopelvic sarcomas that can cause it depending on their origin: retroperitoneal sarcomas, uterine sarcomas, and visceral/peritoneal sarcomas of GIST (gastrointestinal stromal tumor) and non-GIST origin. This article shows the results of sarcoma experts' voting on the recommendations presented during the I Ibero-American Consensus on the Management of Peritoneal Sarcomatosis, which took place during the recent celebration of the III Hispanic-Portuguese Meeting for Updates on the Treatment of Sarcomas.

Electronic Glycemic Management System Improved Glycemic Control and Reduced Complications in Patients With Diabetes Undergoing Coronary Artery Bypass Surgery: A Randomized Controlled Trial.

BACKGROUND: In-hospital hyperglycemia poses significant risks for patients with diabetes mellitus undergoing coronary artery bypass graft (CABG) surgery. Electronic glycemic management systems (eGMSs) like InsulinAPP offer promise in standardizing and improving glycemic control (GC) in these settings. This study evaluated the efficacy of the InsulinAPP protocol in optimizing GC and reducing adverse outcomes post-CABG. METHODS: This prospective, randomized, open-label study was conducted with 100 adult type 2 diabetes mellitus (T2DM) patients post-CABG surgery, who were randomized into two groups: conventional care (gCONV) and eGMS protocol (gAPP). The gAPP used InsulinAPP for insulin therapy management, whereas the gCONV received standard clinical care. The primary outcome was a composite of hospital-acquired infections, renal function deterioration, and symptomatic atrial arrhythmia. Secondary outcomes included GC, hypoglycemia incidence, hospital stay length, and costs. RESULTS: The gAPP achieved lower mean glucose levels (167.2 ± 42.5 mg/dL vs 188.7 ± 54.4 mg/dL; P = .040) and fewer patients-day with BG above 180 mg/dL (51.3% vs 74.8%, P = .011). The gAPP received an insulin regimen that included more prandial bolus and correction insulin (either bolus-correction or basal-bolus regimens) than the gCONV (90.3% vs 16.7%). The primary composite outcome occurred in 16% of gAPP patients compared with 58% in gCONV (P < .010). Hypoglycemia incidence was lower in the gAPP (4% vs 16%, P = .046). The gAPP protocol also resulted in shorter hospital stays and reduced costs. CONCLUSIONS: The InsulinAPP protocol effectively optimizes GC and reduces adverse outcomes in T2DM patients' post-CABG surgery, offering a cost-effective solution for inpatient diabetes management.

Safety of CoronaVac and ChAdOx1 vaccines against SARS-CoV-2 in patients with rheumatoid arthritis: data from the Brazilian multicentric study safer.

BACKGROUND: Patients with immune-mediated rheumatic diseases (IMRDs) have been prioritized for COVID-19 vaccination to mitigate the infection severity risks. Patients with rheumatoid arthritis (RA) are at a high risk of severe COVID-19 outcomes, especially those under immunosuppression or with associated comorbidities. However, few studies have assessed the safety of the COVID-19 vaccine in patients with RA. OBJECTIVE: To evaluate the safety of vaccines against SARS-CoV-2 in patients with RA. METHODS: This data are from the study "Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases," a Brazilian multicentric prospective phase IV study to evaluate COVID-19 vaccine in IMRDs in Brazil. Adverse events (AEs) in patients with RA of all centers were assessed after two doses of ChAdOx1 (Oxford/AstraZeneca) or CoronaVac (Sinovac/Butantan). Stratification of postvaccination AEs was performed using a diary, filled out daily and returned at the end of 28 days for each dose. RESULTS: A total of 188 patients with RA were include, 90% female. CoronaVac was used in 109 patients and ChAdOx1 in 79. Only mild AEs were observed, mainly after the first dose. The most common AEs after the first dose were pain at the injection (46,7%), headache (39,4%), arthralgia (39,4%), myalgia (30,5%) and fatigue (26,6%), and ChAdOx1 had a higher frequency of pain at the injection (66% vs 32 %, p < 0.001) arthralgia (62% vs 22%, p < 0.001) and myalgia (45% vs 20%, p < 0.001) compared to CoronaVac. The more common AEs after the second dose were pain at the injection (37%), arthralgia (31%), myalgia (23%), headache (21%) and fatigue (18%). Arthralgia (41,4% vs 25%, p = 0.02) and pain at injection (51,4% vs 27%, p = 0.001) were more common with ChAdOx1. No serious AEs were related. With Regard to RA activity level, no significant difference was observed between the three time periods for both COVID-19 vaccines. CONCLUSION: In the comparison between the two immunizers in patients with RA, local reactions and musculoskeletal symptoms were more frequent with ChAdOx1 than with CoronaVac, especially after the first dose. In summary, the AE occurred mainly after the first dose, and were mild, like previous data from others immunizing agents in patients with rheumatoid arthritis. Vaccination did not worsen the degree of disease activity.

Lipid biomarker profile of the Permian organic-rich shales (Irati Formation) in the northernmost of Parana Basin, Brazil.

The Irati Formation (Paraná Basin) is a mixed carbonate and organic-rich shale sequence intruded by Jurassic-Cretaceous basic rocks, featuring Brazil's most important oil shale deposits with different maturity levels. For the first time, the distribution of oil shale biomarkers from an outcrop section (quarry) of the Irati Formation in the northernmost Paraná Basin was analyzed by GC-MS and GC-MS/MS to determine the thermal evolution, organic matter origin and the depositional paleoenvironment. The organic-rich shale at the northernmost border of the basin has high similarity with the central and southernmost areas, indicating a primary control able to induce cyclic sedimentation in a broad (106 km2) and restricted environment. PCA and HCA analysis of bulk and molecular parameters showed changes in the organic matter composition and paleoenvironmental conditions throughout the stratigraphic column. Nonetheless, there are significant differences compared to the central-eastern and southern areas of the basin. Contrasting with the southern region, the north, predominates biphytane, low and medium gammacerane index. Pr/n-C17, Ph/n-C18, HI and OI values suggest type II/III kerogen from marine organic matter with freshwater input. Among the steranes, those of stereochemistry ααα 20R predominate over ααα 20S, and the presence of ßTm indicates the shales are less thermally evolved.

Profile of cattle breed sensitivity to the tick Rhipicephalus microplus.

Among cattle, Bos taurus breeds and their crosses are more sensitive to tick infestations than Bos indicus breeds that are more resistant to infestation and more adaptable to tropical climates. The presence of susceptible individuals in herds and inadequate tick control lead to direct and indirect losses in the meat production chain, in addition to increased mortality due to cattle tick fever. The objective of this study was to describe, compare and rank the sensitivity of different breeds of stabled cattle to the tick Rhipicephalus microplus and to present, as an innovative result, a scale called the Tick Ruler. Secondary data on the number of retrieved engorged females, engorged female ticks' weight, egg mass weight and number of larvae were extracted from research reports of experiments conducted over 18 years with eight breeds to describe and report the sensitivity of the breeds to artificial infestation by R. microplus larvae. For analyses, the recovery rate of engorged female ticks and the percentile of dispersion of individuals in their respective races were calculated, and comparison of these percentiles between races was performed. The ranking of the percentiles resulted in the organization of the breeds by their susceptibility to R. microplus; we call this scale the "Tick Ruler." The ruler is a simple, easy-to-understand tool that can be used by technicians and producers to evaluate the tick sensitivity of a breed of interest and can assist producers in decision-making to find a balance between increased production gains and the risk of economic losses depending on the breed composition in a cattle herd.

Multi-trait index: selection and recommendation of superior black bean genotypes as new improved varieties.

Common bean provides diet rich in vitamins, fiber, minerals, and protein, which could contribute into food security of needy populations in many countries. Developing genotypes that associate favorable agronomic and grain quality traits in the common bean crop could increase the chances of adopting new cultivars black bean. In this context, the present study aimed at selection of superior black bean lines using multi-variate indexes, Smith-Hazel-index, and genotype by yield*trait biplot analysis. These trials were conducted in Campos dos Goytacazes - RJ, in 2020 and 2021. The experimental design used was randomized blocks, with 28 treatments and three replications. The experimental unit consisted of four rows 4.0 m long, spaced at 0.50 m apart, with a sowing density of 15 seeds per meter. The two central rows were used for the evaluations. The selection of superior genotypes was conducted using the multiple trait stability index (MTSI), multi-trait genotype-ideotype distance index (MGIDI), multi-trait index based on factor analysis and genotype-ideotype distance (FAI-BLUP), Smith-Hazel index, and Genotype by Yield*Trait Biplot (GYT). The multivariate indexes efficiently selected the best black bean genotypes, presenting desirable selection gains for most traits. The use of multivariate indexes and GYT enable the selection of early genotypes with higher grain yields. These lines G9, G13, G17, G23, and G27 were selected based on their performance for multiple traits closest to the ideotype and could be recommended as new varieties.

Clinical profiles and treatment outcomes of outpatients with interstitial lung disease and mechanic's hands: A retrospective and observational cohort.

Idiopathic inflammatory myopathies, especially antisynthetase syndrome, often appear outside of the muscles as interstitial lung disease (ILD). Another typical finding is the presence of mechanic's hands. The aim of the present study was to describe the clinical, functional, tomographic, and serological data of patients with ILD and mechanic's hands and their response to treatment and survival rates. This is a retrospective study of ILD with concurrent myopathy. Among the 119 patients initially selected, 51 had mechanic's hands. All the patients were screened for anti-Jo-1 antibodies. An expanded panel of myopathy autoantibodies was also performed in 27 individuals. Of the 51 patients, 35 had 1 or more antibodies. The most common were anti-Jo-1, anti-PL-7, and anti-PL-12, while of the associated antibodies, anti-Ro52 was present in 70% of the 27 tested individuals. A significant response to treatment was characterized by an increase in predicted forced vital capacity (FVC) of at least 5% in the last evaluation done after 6 to 24 months of treatment. A decrease in predicted FVC of at least 5%, the need for oxygen therapy, or death were all considered treatment failures. All patients were treated with corticosteroids, and 71% with mycophenolate. After 24 months, 18 patients had an increase in FVC, 11 had a decrease, and 22 remained stable. After a median follow-up of 58 months, 48 patients remained alive and three died. Patients with honeycombing on high-resolution chest tomography (log-rank = 34.65; P < .001) and a decrease in FVC ≥5% (log-rank = 18.28, P < .001) had a poorer survival rate. Patients with ILD and mechanic's hands respond well to immunosuppressive treatment.

Effector CD4+ T-cell subsets in Takayasu arteritis-differences between the peripheral blood and the aorta.

Takayasu arteritis (TAK) is a granulomatous vasculitis that affects large arteries. T cells are important in TAK pathophysiology as these cells orchestrate granulomatous infiltration in arteries. This study aims to evaluate effector CD4+ T cells in the peripheral blood and the aortic wall of TAK patients and to analyze associations with disease activity and therapy. We performed a longitudinal study including 30 TAK patients and 30 controls. CD3+ T cells, CD3+CD4- T cells, CD4+ T cells, and Th1, Th2, and Th17 cells were evaluated in peripheral blood by flow cytometry, and the expression of CD4, CD8, Tbet, GATA-3, and RORγT was analyzed in the aorta of six patients by immunohistochemistry. TAK patients presented lower CD3+ T cells and CD4+ T cells (P = 0.031 and P = 0.039, respectively) than controls. Patients with active disease and those in remission had higher proportions of Th17 cells than controls (P = 0.016 and P = 0.004, respectively). Therapy for TAK did not result in significant differences concerning CD4+ effector T-cell subpopulations. Disease duration correlated with the number and percentage of Th2 cells (rho = -0.610 and rho = -0.463, respectively) and with Th17 cells (rho = -0.365 and rho = -0.568). In the aorta, the expression of CD8 was higher than CD4, whereas GATA-3, Tbet, and RORγT were expressed in this order of frequency. In conclusion, TAK patients present an increased Th17 response in the peripheral blood regardless of disease activity, whereas in the aortic tissue CD8 cells and the Th2 response were predominant.

Protein disulfide isomerase-mediated transcriptional upregulation of Nox1 contributes to vascular dysfunction in hypertension.

Nox1 signaling is a causal key element in arterial hypertension. Recently, we identified protein disulfide isomerase A1 (PDI) as a novel regulatory protein that regulates Nox1 signaling in VSMCs. Spontaneously hypertensive rats (SHR) have increased levels of PDI in mesenteric resistance arteries compared with Wistar controls; however, its consequences remain unclear. Herein, we investigated the role of PDI in mediating Nox1 transcriptional upregulation and its effects on vascular dysfunction in hypertension. We demonstrate that PDI contributes to the development of hypertension via enhanced transcriptional upregulation of Nox1 in vascular smooth muscle cells (VSMCs). We show for the first time that PDI sulfenylation by hydrogen peroxide contributes to EGFR activation in hypertension via increased shedding of epidermal growth factor-like ligands. PDI also increases intracellular calcium levels, and contractile responses induced by ANG II. PDI silencing or pharmacological inhibition in VSMCs significantly decreases EGFR activation and Nox1 transcription. Overexpression of PDI in VSMCs enhances ANG II-induced EGFR activation and ATF1 translocation to the nucleus. Mechanistically, PDI increases ATF1-induced Nox1 transcription and enhances the contractile responses to ANG II. Herein we show that ATF1 binding to Nox1 transcription putative regulatory regions is augmented by PDI. Altogether, we provide evidence that HB-EGF in SHR resistance vessels promotes the nuclear translocation of ATF1, under the control of PDI, and thereby induces Nox1 gene expression and increases vascular reactivity. Thus, PDI acts as a thiol redox-dependent enhancer of vascular dysfunction in hypertension and could represent a novel therapeutic target for the treatment of this disease.

IgG4-related disease-rare but you should not forget it.

Immunoglobulin G4-related disease is a systemic immune-mediated disease with insidious evolution characterized by fibroinflammatory lesions over virtually any organ system. Despite the remarkable progression of knowledge, its etiology remains undefined. Due to its relapse-remitting pattern, it could accumulate irreversible damage, increasing comorbidities and mortality. This paper emphasizes key concepts for diagnosing and treating patients with this condition.

Position statement of the Brazilian society of Rheumatology on mesna use as a preventive therapy for bladder disease in patients with systemic autoimmune diseases and systemic vasculitis under cyclophosphamide treatment.

OBJECTIVE: To review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune diseases and systemic vasculitis treated with cyclophosphamide. MATERIALS AND METHODS: The search for articles was conducted systematically through MEDLINE, LILACS, Cochrane Library, and Embase databases. Only articles in English were selected. For available records, titles and abstracts were selected independently by two investigators. RESULTS: Eighteen studies were selected for analysis. The known adverse effects of cyclophosphamide were hematological toxicity, infections, gonadal toxicity, teratogenicity, increased risk for malignancy and hemorrhagic cystitis. Long-term toxicity was highly dependent on cyclophosphamide cumulative dose. The risk of bladder cancer is especially higher in long-term exposure and with cumulative doses above 36 g. The risk remains high for years after drug discontinuation. Hemorrhagic cystitis is highly correlated with cumulative dose and its incidence ranges between 12 and 41%, but it seems to be lower with new regimens with reduced cyclophosphamide dose. No randomized controlled trials were found to analyze the use of mesna in systemic autoimmune rheumatic diseases and systemic vasculitis. Retrospective studies yielded conflicting results. Uncontrolled prospective studies with positive results were considered at high risk of bias. No evidence was found to support the use of mesna during the treatment with cyclophosphamide for autoimmune diseases or systemic vasculitis to prevent hemorrhagic cystitis and bladder cancer. In the scenarios of high cumulative cyclophosphamide dose (i.e., > 30 g), patients with restricted fluid intake, neurogenic bladder, therapy with oral anticoagulants, and chronic kidney disease, mesna could be considered. CONCLUSION: The current evidence was found to be insufficient to support the routine use of mesna for the prophylaxis of hemorrhagic cystitis and bladder cancer in patients being treated for systemic autoimmune diseases and systemic vasculitis with cyclophosphamide. The use may be considered for selected cases.

Distinct immunometabolic signatures in circulating immune cells define disease outcome in acute-on-chronic liver failure.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis characterized by multiple organ failure and high short-term mortality. The pathophysiology of ACLF involves elevated systemic inflammation leading to organ failure, along with immune dysfunction that heightens susceptibility to bacterial infections. However, it is unclear how these aspects are associated with recovery and nonrecovery in ACLF. APPROACH AND RESULTS: Here, we mapped the single-cell transcriptome of circulating immune cells from patients with ACLF and acute decompensated (AD) cirrhosis and healthy individuals. We further interrogate how these findings, as well as immunometabolic and functional profiles, associate with ACLF-recovery (ACLF-R) or nonrecovery (ACLF-NR). Our analysis unveiled 2 distinct states of classical monocytes (cMons). Hereto, ACLF-R cMons were characterized by transcripts associated with immune and stress tolerance, including anti-inflammatory genes such as RETN and LGALS1 . Additional metabolomic and functional validation experiments implicated an elevated oxidative phosphorylation metabolic program as well as an impaired ACLF-R cMon functionality. Interestingly, we observed a common stress-induced tolerant state, oxidative phosphorylation program, and blunted activation among lymphoid populations in patients with ACLF-R. Conversely, ACLF-NR cMon featured elevated expression of inflammatory and stress response genes such as VIM , LGALS2 , and TREM1 , along with blunted metabolic activity and increased functionality. CONCLUSIONS: This study identifies distinct immunometabolic cellular states that contribute to disease outcomes in patients with ACLF. Our findings provide valuable insights into the pathogenesis of ACLF, shedding light on factors driving either recovery or nonrecovery phenotypes, which may be harnessed as potential therapeutic targets in the future.

Cerebrovascular disease in patients with antiphospholipid antibody syndrome: a transcranial Doppler and magnetic resonance imaging study.

Objective: Transcranial Doppler (TCD) and brain MRI may be useful in evaluating patients with APS, helping to stratify the risk of cerebrovascular ischaemic events in this population. This study aimed to assess the frequency of brain MRI abnormalities in patients with primary antiphospholipid syndrome, secondary antiphospholipid syndrome and SLE and correlate to TCD findings. Methods: The study, conducted over four years at two autoimmune disease referral centres, included 22 primary antiphospholipid syndrome patients, 24 secondary antiphospholipid syndrome patients, 27 SLE patients without APS and 21 healthy controls. All participants underwent TCD to assess cerebral haemodynamics, detect microembolic signals and evaluate right-to-left shunts, followed by brain MRI and magnetic resonance angiography. MRI scans were reviewed for acute microembolism, localized cortical infarctions, border infarctions, lacunar infarctions, ischaemic lesions, white matter hyperintensity, micro and macro haemorrhages and arterial stenosis ≥50% of the cervical carotid artery, by two neuroradiologists blinded to the clinical data. Results: Brain MRI findings were similar between the groups, except for lacunar infarction, more frequent in patients with secondary antiphospholipid syndrome (P = 0.022). Patients with intracranial stenosis detected by TCD had a higher frequency of territorial infarction (40% vs 7.5%, P = 0.02), lacunar (40% vs 11.3%, P = 0.075) and border zone infarcts (20% vs 1.9%, P = 0.034). Conclusions: Patients with intracranial stenosis presented a higher frequency of territorial, lacunar and border zone infarcts, suggesting that evaluating the intracranial vasculature should not be neglected in patients with APS and stroke.

Evaluation of common femoral vein thickness as a diagnostic tool for Behçet's disease in a non-endemic area.

OBJECTIVES: To evaluate common femoral vein thickness (CFVT) as a diagnostic tool in Brazilian patients with Behçet's disease (BD) and to analyse associations between increased CFVT and disease features. METHODS: A cross-sectional study was performed including 100 BD patients and 100 controls. The CFVT and the diameters of great saphenous vein (GSV), and small saphenous vein (SSV) were measured by Doppler ultrasound. RESULTS: BD patients had higher right CFVT [0.600mm (0.500-0.700) vs. 0.525mm (0.450-0.637); p=0.012] and left CFVT [0.550mm (0.450-0.650) vs. 0.500mm (0.450-0.550); p=0.004] compared to controls. Vascular involvement of BD and previous deep venous thrombosis were associated with increased CFVT (p<0.05). The number of vascular events correlated with right and left CFVT (Rho = 0.475 p=0.030 and Rho = 0.429 p=0.052, respectively). The 0.575mm cut-off point of right and left CFVT had area under the curve (AUC) of 0.602; 95% confidence interval (95% CI): 0.524-0.680 and AUC: 0.615; 95% CI: 0.537-0.693, respectively. The right and left CFVT had a sensitivity for BD diagnosis of 52% and 43%, and a specificity of 64% and 77%, respectively. No significant differences were found between BD patients and controls regarding the GSV and SSV diameters in both legs (p>0.05). CONCLUSIONS: In this study, CFVT measurement was not shown to be a reliable diagnostic test for BD. CFVT was increased in BD patients presenting vascular involvement and correlated with the number of previous events.

Unveiling the clinical spectrum of relapsing polychondritis: insights into its pathogenesis, novel monogenic causes, and therapeutic strategies.

Relapsing polychondritis is a rare multisystem disease involving cartilaginous and proteoglycan-rich structures. The diagnosis of this disease is mainly suggested by the presence of flares of inflammation of the cartilage, particularly in the ears, nose or respiratory tract, and more rarely, in the presence of other manifestations. The spectrum of clinical presentations may vary from intermittent episodes of painful and often disfiguring auricular and nasal chondritis to an occasional organ or even life-threatening manifestations such as lower airway collapse. There is a lack of awareness about this disease is mainly due to its rarity. In 2020, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, a novel autoinflammatory syndrome, was described. VEXAS syndrome is attributed to somatic mutations in methionine-41 of UBA1, the major E1 enzyme that initiates ubiquitylation. This new disease entity connects seemingly unrelated conditions: systemic inflammatory syndromes (relapsing chondritis, Sweet's syndrome, and neutrophilic dermatosis) and hematologic disorders (myelodysplastic syndrome or multiple myeloma). Therefore, this article reviews the current literature on both disease entities.