Bronchiectasis, lymphadenopathies related to BAFF overexpression and lymphoplasmacytic cystitis as adverse events associated with prolonged use of rituximab in systemic autoimmune rheumatic diseases.

BACKGROUND: The long-term use of rituximab (RTX) has been gaining ground in the treatment of systemic autoimmune diseases. The adverse events (AEs) associated with its use different to infections are being reported. METHODS: A cohort of patients with SAIDs treated at a high-complexity center in Cali (southwestern Colombia) with follow-up from January 2008 to December 2022 were examined to search for potential AEs associated with prolonged use of RTX. RESULTS: From 178 patients with long-term use of RTX 3 (1.68%) had lymphadenopathies with lymphoid follicular hyperplasia related to BAFF overexpression, 4 (2.24%) with bronchiectasis, and 4 (2.24%) with lymphoplasmacytic cystitis. CONCLUSION: Bronchiectasis, lymphoid follicular hyperplasia related to BAFF overexpression, and lymphoplasmacytic cystitis may be life-threatening long-term AEs in patients with prolonged use of RTX.

Elevation of serum ferritin levels for predicting a poor outcome in hospitalized patients with influenza infection.

OBJECTIVES: There is increasing evidence that ferritin is a key marker of macrophage activation, but its potential role in influenza infection remains unexplored. Our aim was to assess whether hyperferritinaemia (ferritin ≥500 ng/mL) could be a marker of poor prognosis in hospitalized patients with confirmed influenza A infection. METHODS: We prospectively recruited all hospitalized adult patients who tested positive for the influenza A rRT-PCR assay performed on respiratory samples in two consecutive influenza periods (2016-17 and 2017-18). Poor outcome was defined as the presence of at least one of the following: respiratory failure, admission to the intensive care unit, or in-hospital mortality. RESULTS: Among 494 patients, 68 (14%) developed poor outcomes; 112 patients (23%) had hyperferritinaemia (39/68, 57% in the poor-outcome group versus 73/426, 17% in the remaining patients, p < 0.0001). Median serum ferritin levels were significantly higher in the subgroup of patients with poor outcomes (609 ng/mL, range 231-967 versus 217 ng/mL, range 140-394, p < 0.0001). In multivariate analysis, hyperferritinaemia was associated with a five-fold increase in the odds ratio of developing poor outcome. After adjusting for classic influenza risk factors, ferritin remained as a significant predictive factor in all exploratory models. Ferritin levels had a good discriminative capacity with an area under the ROC curve of 0.72 (95% confidence interval (CI) 0.65-0.8, p < 0.001) and an overall diagnostic accuracy for predicting poor outcome of 79.3% (95%CI 75.4-82.7%). CONCLUSIONS: Serum ferritin may discriminate a subgroup of patients with influenza infection who have a higher risk of developing a poor outcome.

Neutrophil CD64 expression, procalcitonin and presepsin are useful to differentiate infections from flares in SLE patients with SIRS.

Background/Objective Differentiating systemic lupus erythematosus (SLE) activity from infections in febrile patients is difficult because of similar initial clinical presentation. The aim of this study is to evaluate the usefulness of a number of biomarkers for differentiating infections from activity in SLE patients admitted with systemic inflammatory response (SIRS). Methods Patients with SLE and SIRS admitted to the emergency room were included in this study. Measurements of different markers including procalcitonin, neutrophil CD64 expression and presepsin, were performed. Infection was considered present when positive cultures and/or polymerase chain reaction were obtained. Sensitivity and specificity were calculated for all biomarkers. Results Twenty-seven patients were admitted, 23 women (82.5%), mean age 33.2 years. An infectious disease was confirmed in 12 cases. Markers for SLE activity including anti-DNA titers by IIF ( p = 0.041) and enzyme-linked immunosorbent assay ( p = 0.009) were used for differentiating SLE flares from infection. On the contrary, increased procalcitonin ( p = 0.047), neutrophil CD64 expression by flow cytometry ( p = 0.037) and presepsin ( p = 0.037) levels were observed in infected SLE patients. Conclusions High neutrophil CD64 expression, presepsin and procalcitonin levels are useful to differentiate infections from activity in SLE patients. In most cases, a positive bioscore that includes these three markers demonstrate the presence of an infectious disease.

Blend design tools for Medium Combustion Plants (MCP) firing biomass wastes.

A feasible alternative for agricultural or forestry waste management is the operation of a distributed network of sustainable Medium Combustion Plants (MCPs). However, one of the main factors that hinder its development is the propensity to operational problems derived from corrosion, slagging and fouling characteristics of both bottom and fly ashes. Therefore, a cost-effective approach for these multi-product MCP could be based on predictive tools for an optimal formulation of a fuel blend. This work focuses on the assessment of the ability of these methods to provide guidance for preventing ash-related operational problems and to provide fuel-blending rules. The more widespread tools pertain to two types: compositional classification based on chemical analysis of laboratory ashes, and thermodynamic prediction of the most likely species and phases. Both criterion numbers and compositional maps are ranking methods based on the chemical analysis at a given ashing temperature. Thermodynamic equilibrium modeling is not constrained by any difference in the physical conditions of the MCP compared to those in the laboratory. Both kind of prediction tools have been validated in an MCP firing olive tree pruning residues as well as its typical blends in order to mimic a plausible pattern of fuels along a full year operating campaign. An intensive experimental campaign encompasses plant monitoring and off-line analysis of the ashes along the process line. Interpretation of compositional plots has revealed to be potentially sensitive to ashing temperature. Here are presented examples showing how this variable could lead to either insignificant differences or to a substantial disparity in the a priori fuel diagnosis. Some inconsistencies have been observed between the predictions based on criterion numbers, even for the same fuel and for ranking rules specifically formulated for biomasses. Moreover, it does not match consistently with the information obtained from phase diagrams. Therefore, their use should be limited to the case of a well-established selection of a fuel index for a well-defined fuel provided empirical evidence of an enough good description of the ash behavior, which is not the most frequent case. Thermodynamic equilibrium calculations allow a more precise prediction of the main species in the condensed phase, without the constraint of the ashing temperature. Elemental closure of main ash-forming elements with the chemical analysis of the process ashes presents small differences, and their proximity localization on the phase diagrams denote similar prediction between predicted and process ashes.

Profile of BAFF and its receptors' expression in lupus nephritis is associated with pathological classes.

Background/Objective B-cell activating factor (BAFF) plays an important role in the pathogenesis of systemic lupus erythematosus. However, the role of BAFF in lupus nephritis (LN) is not understood. Our aim was to evaluate the expression of BAFF and its three receptors in renal biopsy samples from patients with LN and investigate a relationship with pathological class. Methods We conducted a prospective descriptive study (2011-2014) on 52 kidney biopsy samples from patients with LN. Immunohistochemistry for BAFF, its receptors (transmembrane activator and calcium modulator and cyclophilin ligand interaction (TACI), protein maturation of B cells (BCMA), and BAFF-receptor (BAFF-R)), and CD20 expression was performed. Samples were scored according to the percentage of cells with positive expression. Results In class II LN, BAFF-R and TACI were not expressed, whereas BCMA and BAFF were lowly expressed in the interstitial inflammatory infiltrates. Proliferative class III/IV had elevated BAFF expression in the glomeruli, and TACI was expressed in interstitial inflammatory infiltrates and the glomeruli. Interestingly, the class IV cases with vasculopathy ( n = 4) had endothelial BAFF expression, which was not visible in thrombotic microangiopathy ( n = 4). Class V was characterized by low BAFF expression in interstitial inflammatory infiltrates and by BAFF, TACI, and BCMA expression in the glomeruli. BAFF expression was associated with inflammatory scores and CD20 positive infiltrates, mainly in class IV. Conclusions Expression patterns of BAFF and its receptors differ according to LN class. Our study provides evidence that BAFF could be used as a routine marker in LN biopsies and to determine which patients will benefit from anti-BAFF therapy.

Worsening of calcinosis cutis with teriparatide treatment in two osteoporotic patients.

We present two cases of patients with systemic autoimmune diseases (one with dermatomyositis and one with CREST syndrome) who presented with a worsening of calcinosis cutis after treatment of osteoporosis with teriparatide. To our knowledge, this association is not described in the literature and might be considered in the spectrum of adverse reactions to teriparatide.

Direct oral anticoagulants in antiphospholipid syndrome: a real life case series.

AIM: The aim of this study was to describe a case series of patients with primary or secondary antiphospholipid syndrome (APS) treated with direct oral anticoagulants (DOACs). PATIENTS AND METHODS: Clinical charts of eight patients with thrombotic primary or secondary APS treated with direct oral anticoagulants (DOACs) between January 2012 and May 2015 were reviewed. RESULTS: The mean age was 45 ± 14.36 (range 27-69 years). Four patients had secondary APS (50%). All patients were initially treated with warfarin by a mean time of 70.87 ± 57.32 months (range 17-153 months). Changes in anticoagulation were defined by recurring thrombosis in five patients (62.5%) and life-threatening bleeding in the other three cases. Seven patients (87.5%) received rivaroxaban treatment and one patient (12.5%) apixaban. The mean follow-up period with DOACs was 19 ± 10.06 months (range 2-36 months). There was no recurrence of thrombosis by the time of data collection. CONCLUSIONS: Despite not being the standard treatment in APS, we propose DOACs as a rational alternative for the management of patients with this diagnosis. Further interventional clinical studies are necessary for possible standardization of this therapy in APS patients.

Soluble or soluble/membrane TNF-α inhibitors protect the brain from focal ischemic injury in rats.

Tumor Necrosis Factor-alpha (TNF-α) is an immunomodulatory and proinflammatory cytokine implicated in neuro-inflammation and neuronal damage in response to cerebral ischemia. The present study tested the hypothesis that anti-TNF-α agents may be protective against cerebral infarction. Transient focal ischemia was artificially induced in anesthetized adult male Wistar rats (300-350 g) by middle cerebral artery occlusion (MCAO) with an intraluminal suture. TNF-α function was interfered with either a chimeric monoclonal antibody against TNF-α (infliximab-7 mg/kg) aiming to TNF-α soluble and membrane-attached form; or a chimeric fusion protein of TNF-α receptor-2 with a fragment crystallizable (Fc) region of IgG1 (etanercept-5 mg/kg) aiming for the TNF-α soluble form. Both agents were administered intraperitoneally 0 or 6 h after inducing ischemia. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride staining. Cerebral infarct volume was significantly reduced in either etanercept or infliximab-treated group compared with non-treated MCAO rats 24 h after reperfusion. These results suggest that anti-TNF-α agents may reduce focal ischemic injury in rats.

The importance of evolution in the development and course of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a complex autoimmune disease of recent evolutionary origin. Genetic drift determines diverse polymorphisms implicated in the susceptibility to RA including the major histocompatibility complex (MHC) class II genes in the so-called shared epitope. These genes originated after the divergence between Homo and Pan from their common ancestry Ardipithecus ramidus about 5 million years ago. Natural selection determined the particular changes in the legs (bipedal position), hands, neck, brain and eusociality in humans which influence the clinical presentation of RA. In this article, we hypothesized that the origin and course of RA may be explainable in the light of evolution.

Pneumocystis jirovecii pneumonia in two patients with systemic lupus erythematosus after rituximab therapy.

New cases of Pneumocystis jirovecii pneumonia (PJP) have recently been reported in patients with systemic lupus erythematosus (SLE) after rituximab therapy. Several factors may contribute to susceptibility to P. jirovecii infection in this type of patients, including the immunological characteristics of the disease, the mechanisms of rituximab action, environmental factors, and the biological characteristics of the fungus. We report two patients with SLE who developed PJP after rituximab therapy.

Multiple endovascular stent-graft implantations in a patient with aortic thoracic and abdominal aneurysms due Takayasu arteritis.

We report an adult female patient with Takayasu arteritis (TA) receiving conventional medical treatment and anti-TNF therapy, which developed progressive thoracic and abdominal aortic aneurysms. She developed imminent rupture of the thoracic aneurysm and an endovascular stent-graft (EVSG) was emergency implanted and a year after this procedure the abdominal aneurysm increased in size requiring reoperation and placement of another EVSG. Both procedures had a very good outcome. This case shows the effectivity and security of multiple EVSG implantations in multiple aortic aneurisms in patients with TA.

Is primary hyperparathyroidism a pathogenic factor in some conditions mediated by B lymphocytes hyperactivity?

Several clinical cases have shown the association of primary hyperparathyroidism and immune conditions related to B-cell hyperactivity. In some of these cases the treatment of hyperparathyroidism led to the resolution of the autoimmune phenomena. Thus, this paper hypothesizes that high levels of parathyroid hormone (PTH) may modify B lymphocytes function and induce the development of autoimmunity mediated by B-cell hyperactivity.

Overinfection by Paracoccidioides brasiliensis in Gouty Crystal Arthritis.

Paracoccidioidomycosis is an endemic South American systemic mycosis caused by the dimorphic fungus Paracoccidioides brasiliensis (P. brasiliensis). The main clinical form of disease is pulmonary, but all organs may be involved. We report a case of overinfection by P. brasiliensis in chronic gouty arthritis affecting the proximal phalanx of the right hallux. The patient required proximal amputation and long-term antifungal therapy.

Psychiatric manifestations in patients with dysautonomy associated with systemic lupus erythematosus.

The psychiatric manifestations of three patients with systemic lupus erythematosus (SLE) and neuropathic dysautonomic processes are described. All patients had a severe form of SLE with neurological, renal, articular, pulmonary or haematological manifestations. All three have two types of psychiatric manifestations: (1) a chronic and progressive depression and (2) a complex dissociative disorder during the acute episodes of postural hypotension. A provocative test with SPECT with 99mTc-HmPAO to be done during the episode of orthostatic hypotension may contribute to clinical assessment of complex changes in cerebral regional perfusion.

Acute Generalized Exanthematous Pustulosis due to Tocilizumab in a Rheumatoid Arthritis Patient.

We report a female patient with rheumatoid arthritis which was refractory to methotrexate, leflunomide, and anti-TNF therapy. She was treated with anti-IL-6 tocilizumab (TCZ), with an early appearance of sterile pustules on erythematous swollen skin of trunk, back, and abdominal area. The lesions were consistent with the diagnosis of acute drug-related generalized exanthematous pustulosis (AGEP). This adverse event was controlled with medical treatment without requiring removal of TCZ.

Patients with relapsing polychondritis and previous cartilage trauma present more autoimmunity phenomena.

Relapsing polychondritis (RP) is an autoimmune disease characterized by inflammation and destruction of all type of body cartilage, and the cartilage trauma may be a trigger of the disease in a susceptible person. We describe the clinical and laboratory findings in a group of 18 patients with RP with (7 cases) or without (11 cases) anteceding cartilage trauma. The mean age was 41 years in the group with cartilage trauma and 55 years in the group without cartilage trauma. For both groups, female gender was predominant. All patients presented with auricular chondritis. Systemic manifestations and autoimmunity were more common in patients with anteceding trauma.

Biochemical comparison of venoms from young Colombian Crotalus durissus cumanensis and their parents

Crotalus durissus cumanensis, a rattlesnake endemic to Colombia and Venezuela, is considered one of the most lethal snake species in Latin America. The aim of the present study was to compare the protein content and biological activity of the venom obtained from eight specimens of C. durissus cumanensis, namely two adults from different localities of Colombia and six offspring born in captivity. Protein profiles of crude venoms were analyzed by SDS-PAGE and RP-HPLC, and biological activities were evaluated for lethality, edema, defibrination, hemolytic and coagulant activities to assess individual venoms of adults and a pool of young snake venoms. Transient edema appeared rapidly after venom inoculation, whereas hemorrhagic effect was not observed. Differences in protein profiles, lethality, hemolytic, coagulant and defibrinating activities between both adult snake venoms were observed; those from the mother snake exhibited higher activities. Venoms from young snakes were similar to the one obtained from the mother, but the coagulant effect was stronger in offspring venoms. Notably, biological effects of the father snake venom were not comparable to those previously described for C. durissus cumanensis from Venezuela and C. durissus terrificus from Brazil, confirming the high variability of the venom from Crotalus species.

Clinical and virological effects during two years of ongoing adefovir dipivoxil in the treatment of lamivudine-resistant chronic hepatitis B infection.

OBJECTIVE: Our aim was to evaluate the efficacy and safety of adding adefovir to lamivudine therapy for hepatitis B virus (HBV)-infected patients resistant to Ramivudine. PATIENTS AND METHODS: Among 17 studied patients, 7 had chronic active HBV infection and 10 were posttransplant with HBV infection (9 with de novo HBV). They received lamivudine plus adefovir therapy for 2 years. We assessed reductions in serum HBV-DNA and alanine aminotransferase (ALT) levels, loss of HBeAg (in HBeAg+ cases), and HBsAg clearance. RESULTS: A virological response, as defined by HBV-DNA below the cut off by hybridization, was observed in 12 (70.6%) patients and loss of HBeAg in 4 (44.4%) of the 9 initially HBeAg-positive cases. A biochemical response, defined as a decreased serum ALT to the normal range, occurred in 4 (26.7%) patients. Median serum creatinine increased in 3 of 15 (20%) patients, excluding those on hemodialysis. There were two noteworthy cases of sustained HBsAg seroconversion with adefovir (11.8%): one patient with de novo HBV infection posttransplantation and positive hepatitis C virus-RNA serology, and one patient with decompensated HBV cirrhosis in whom viral replication ceased, making him eligible for transplantation. CONCLUSIONS: Currently, adefovir is an effective rescue therapy that broadens the existing range of options for patients with lamivudine-resistant chronic hepatitis B infection, particularly those with decompensated cirrhosis awaiting a liver graft, and those with recurrent posttransplantation HBV. The relatively small biochemical response seen in these patients may be attributable to the high prevalence of concomitant hepatitis C virus infection (41%).

Quantifying energy dissipation by grazing animals in harsh environments.

Grazing systems in harsh environments are common throughout the world, and animal production is the mainstay of the livelihoods of many resource-poor farmers. The energy cost of the various activities involved in the process of harvesting the pasture to transform it into animal product can be estimated through an energy balance. This cost would be the difference between the metabolizable energy intake (MEI) and the energy expenditures for maintenance (MEm), temperature regulation (MEtr), and the energy for production (MEp). Each of the ME has its own net energy (NE) and its associated efficiency (K). When MEI>MEm+MEtr+MEp, the difference is attributable to the energy dissipated during grazing. The efficiency of converting the energy consumed into animal products depends on the magnitude of the dissipation. The inefficiency is associated with the energy spent in locomotion and the stress produced when there is low availability of energy in the pasture. This paper presents a method to quantify the dissipation of energy by grazing animals by considering it as a function of available energy. Such an understanding is required in order to develop management strategies to increase conversion efficiency.