Management of postinfectious inflammatory arthritis.

PURPOSE OF REVIEW: Postinfectious inflammatory arthritis can result from various pathogens, including bacteria, viruses, fungi, and parasites. Prompt identification and treatment of acute infection is vital, but some cases progress to chronic arthritis despite successful treatment of infection. Postinfectious inflammatory arthritis varies from mild, self-limited arthralgia to severe, refractory arthritis, necessitating ongoing disease-modifying treatment. This review explores the spectrum of postinfectious inflammatory arthritis to provide insights into effective management. RECENT FINDINGS: Research continues regarding the benefit of antimicrobial therapy, beyond treatment of the acute infection, to diminish the severity of postinfectious inflammatory arthritis. Following treatment of acute infection, most cases are self-limited so treatment is symptomatic. However, a difficult-to-predict fraction of cases develop chronic postinfectious inflammatory arthritis that can be challenging to manage. Recently, as more biologic, and targeted synthetic DMARDs have become available, treatment options have expanded. SUMMARY: In this article, we use the term 'postinfectious inflammatory arthritis' rather than 'reactive arthritis' because it describes a broader spectrum of diseases and emphasizes the common pathogenesis of a postinfectious inflammatory process. We summarize the conventional therapies and recent management developments for the most frequently encountered postinfectious inflammatory arthritides.

Extra-articular Manifestations of Chikungunya.

Chikungunya fever (CHIK) is a neglected tropical disease associated with chronic arthritis. CHIK is usually a self-limiting condition; however, extra-articular manifestations present as atypical illness in a minority of patients. These atypical features may mimic other conditions and potentially distract physicians from the true diagnosis. This review analyzes the evidence of many unusual extra-articular manifestations reported in cases of CHIK. Depending on the affected system, these unusual manifestations include encephalitis, myocarditis, acute interstitial nephritis, cutaneous manifestations, acute anterior uveitis, abdominal pain, and depression. In addition, coinfections and comorbidities may cause atypical illness and obscure the diagnosis. Further studies are required to clarify the pathophysiology and natural history of CHIK, as it remains a burdening condition. Exploring its atypical symptoms may be the missing scientific piece of this puzzle.

Mineral bioaccessibility in 3D printed gels based on milk/starch/ĸ-carrageenan for dysphagic people.

Dysphagia is a condition that affects the ability to chew and swallow food and beverages, having a major impact on people's health and wellbeing. This work developed gel systems with a customized texture suitable for intake by dysphagic people using 3D printing and milk. Gels were developed using skim powdered milk, cassava starch (native and modified by the Dry Heating Treatment (DHT)), and different concentrations of kappa-carrageenan (ĸC). The gels were evaluated in relation to the starch modification process and concentration of gelling agents, 3D printing performance, and suitability for dysphagic people (following both the standard fork test described by the International Dysphagia Diet Standardization Initiative (IDDSI), and also using a new device coupled to a texture analyzer). Moreover, the best formulations were evaluated for mineral bioaccessibility through simulated gastrointestinal digestion based on INFOGEST 2.0 standardized method. The results showed that ĸC had a dominant effect compared to the DHT-modified starch on gel texture, 3D printing performance, and fork tests. The gels obtained by molding or 3D printing resulted in different behaviors during the fork test, which was associated with the gel extrusion process that breaks down their initial structure. The strategies applied to tailor the texture of the milk did not affect the mineral bioaccessibility, which was kept high (>80%).

Pathogenesis of chronic chikungunya arthritis: Resemblances and links with rheumatoid arthritis.

Chikungunya virus (CHIKV) infection results from transmission by the mosquito vector. Following an incubation period of 5-7 days, patients develop an acute febrile illness, chikungunya fever (CHIKF), characterized by high fevers, maculopapular rash, headaches, polyarthritis/arthralgias, myalgias, nausea, vomiting, and diarrhea. Joint pain is often severe, and most often involves the hands, the wrists, the ankles, and the metatarsal-phalangeal joints of the feet. Many patients recover within several weeks, but up to 50% develop chronic joint pain and swelling for more than 12 weeks, then we refer to these symptoms as chronic chikungunya arthritis (CCA). The pathogenesis of CCA is not well understood. In this article, we suggest that mesenchymal stem cells (MSCs) may play an important role in this pathogenesis. This heterogeneous group of multipotent cells, morphologically similar to fibroblasts, may undergo epigenetic changes capable of generating aberrant progenies. However, we believe that there is no need for a latent infection. In our pathogenic hypothesis, CHIKV infection of MSCs would cause epigenetic changes both in MSCs themselves and in their progenies, without the need for reactivation of dormant viruses.

Breast cancer patient-reported outcomes on level 1 and level 2 oncoplastic procedures using BREAST-Q®.

PURPOSE: In breast cancer management not only mortality and surgical morbidity measurements are important but also patient satisfaction indexes. The authors evaluated the satisfaction and health-related quality of life (HRQOL) using the breast-conserving therapy (BCT) and breast reduction (BR) modules of BREAST-Q®. METHODS: This is a cross-sectional study that analyzed breast cancer patients consecutively submitted to breast surgery between January 2011 and April 2018 using two modules of BREAST-Q®. 968 patients were contacted and 232 answers were gathered: 171 patients submitted to oncoplastic level 1 surgery answered the BCT module and 61 submitted to oncoplastic level 2 surgery answered the BR module. Clinical data were retrieved from patients' medical records. RESULTS: Among the 232 questionnaires received, the median scores for psychosocial well-being, sexual well-being and (postoperative) satisfaction with breasts for BCT and BR modules were, respectively, 77.0 and 73.5 (p = 0.17); 62.0 and 53.0 (p = 0.14); 72.0 and 66.0 (p = 0.66). The median of adverse effects of radiation in the BCT module was 87.0. The median satisfaction with outcome in the BR module was 86.0. Both groups of patients revealed high scores of satisfaction with care. For the BCT patients, satisfaction with breasts strongly correlated with sexual well-being and was moderately correlated with psychosocial and physical well-being. For the BR patients, the satisfaction with outcome strongly correlated with satisfaction with medical team and moderately correlated with the remaining scales. CONCLUSION: Both oncoplastic surgery levels yielded similar satisfaction outcomes when assessed using BCT and BR modules of BREAST-Q®.

Extra-articular Manifestations of Chikungunya

ABSTRACT Chikungunya fever (CHIK) is a neglected tropical disease associated with chronic arthritis. CHIK is usually a self-limiting condition; however, extra-articular manifestations present as atypical illness in a minority of patients. These atypical features may mimic other conditions and potentially distract physicians from the true diagnosis. This review analyzes the evidence of many unusual extra-articular manifestations reported in cases of CHIK. Depending on the affected system, these unusual manifestations include encephalitis, myocarditis, acute interstitial nephritis, cutaneous manifestations, acute anterior uveitis, abdominal pain, and depression. In addition, coinfections and comorbidities may cause atypical illness and obscure the diagnosis. Further studies are required to clarify the pathophysiology and natural history of CHIK, as it remains a burdening condition. Exploring its atypical symptoms may be the missing scientific piece of this puzzle.

Evaluation of the Impact of Exposure To Heat and to By-Products of Combustion on the Health of Firefighters.

Firefighters are often exposed to high temperatures and by-products of combustion, which can affect their health. In this study, we assessed the impact of acute exposure of firefighters in fire simulators. Twenty male firefighters were exposed to fire simulators, and observed in four phases: pre-exposure (group 0, control) and after the end of the first (group 1), second (group 2), and fourth (group 3) weeks of training. Blood samples were collected and dosed to evaluate the response of the immune, inflammatory (C-reactive protein, IL6, and IL10), and endocrine systems (cortisone, total testosterone, free testosterone, SHBG, bioavailable testosterone, TSH, and free T4). In groups 0, 1, and 3, a thermographic evaluation was also carried out to study the temperature and body heat flow of the participants. Regarding the inflammatory process, an increase in C-reactive protein and a reduction in IL-10 were observed. With respect to hormonal markers, an increase in cortisol and reduced levels of free T4 and bioavailable testosterone were found after exposure, with recovery of testosterone levels in the final week of training. Thermoregulatory adaptation of the organism has been associated with changes in heat flow in the organism in people subjected to extreme temperatures, with emphasis on the performance of the lower limbs. Our findings demonstrate an inflammatory response with hormonal changes after exposure to fire and an adaptive response of thermal balance, which could aid understanding of the physiology of the human body in extreme situations.

Les sapeurs-pompiers (SP) sont régulièrement exposés à la chaleur et aux produits de combustion, qui peuvent avoir un retentissement sur leur santé. Nous avons évalué l'effet d'une exposition aiguë de 22 SP (tous des hommes) à incendie simulé grâce à la répétition à 4 reprises d'une même batterie d'examens (avant- T0, et à la fin des 1ère -T1 2ème - T2 et 3ème - T3 semaines d'entraînement). Des paramètres sanguins relatifs à l'inflammation et l'immunité (CRP, IL6, IL10) ainsi qu'au système endocrinien (cortisol, testostérones totale, libre et biodisponible, SHBG, TSH et T4 libre) étaient prélevés à chaque évaluation. Une étude thermographique, évaluant la température corporelle et le flux thermique corporel était réalisée à T0, T1 et T3. On constatait une augmentation de la CRP et une baisse de IL10. On observait une augmentation de la cortisolémie ainsi qu'une baisse de thyroxine libre et testostérone biodisponible, cette dernière se normalisant à T3. L'adaptation corporelle à la chaleur se traduit par une augmentation du flux thermique, en particulier aux membres inférieurs. Nous observons donc des réponses inflammatoire comme endocrinienne et une adaptation de la thermorégulation en cas d'exposition à un incendie, constatations pouvant contribuer à la compréhension de la physiologie humaine en situations extrêmes.

Shifts in gut microbiome across five decades of repeated guppy translocations in Trinidadian streams.

An organism's gut microbiome can alter its fitness, yet we do not know how gut microbiomes change as their hosts evolve in the wild. We took advantage of a five-decade 'chronosequence' of translocated fish populations to examine associated changes in the gut microbiome. Populations of Trinidadian guppies have displayed parallel phenotypic convergence six times when moved from high predation (HP) to low predation (LP) environments. Across four drainages, we found microbiomes of fish translocated 5-6 years prior to sampling were already distinct from the microbiomes of their HP source populations. Changes in environmental conditions were most important in driving this shift, followed by phenotypic shifts in gut morphology. After 30-60 years in LP environments, microbiome composition was still distinct from native LP populations, but microbiome function was not. We found some evidence that nitrogen fixation enhanced gut nutrient absorption, but most functional shifts were not parallel across drainages. Stream-and drainage-specific signatures were present for both composition and function, despite our overall finding of consistent microbiome change across drainages. As we unravel the complexities of host-microbiome evolution in the wild, studies should consider environmental microbial colonization, host phenotypic plasticity in nature, and more realistic environmental conditions excluded from laboratory studies.

Initial experience with targeted axillary dissection after neoadjuvant therapy in breast cancer patients.

BACKGROUND: Targeted axillary dissection (TAD) combines sentinel node biopsy (SNB) with the removal of the previously marked metastatic node. TAD is a promising concept for axillary restaging in node-positive breast cancer patients with pathological complete response (pCR) to neoadjuvant therapy (NAT). We aimed to evaluate TAD feasibility in this context. METHODS: A prospective observational study was conducted in biopsy-confirmed cN1 patients. The removal of the clipped node (CN) was guided by intraoperative ultrasound. SNB used indocyanine green and patent blue V dye. If the CN or sentinel lymph nodes (SLN) had any metastatic foci, or the TAD procedure was unsuccessful, the patient underwent axillary lymph node dissection (ALND). RESULTS: Thirty-seven patients were included. TAD and SNB identification rates were 97.3%. Every retrieved CN was also a SLN. At the individual level, SNB identification rate was 89.2% with indocyanine green and 85.5% with patent blue V dye. The CN identification rate was 81.1%, being higher when the CN was localized on the intraoperative ultrasound (84.4% vs 60.0%). Nodal pCR was achieved by 54.1% of our patients and was more frequent in HER2-positive and triple-negative tumors (p = 0.039). Nineteen patients were spared from ALND. CONCLUSION: TAD with intraoperative ultrasound-guided excision of the CN and SNB with indocyanine green and patent blue V dye is a feasible concept to identify patients without axillary residual disease after NAT, that can be spared from ALND, although the need for marking the biopsied node should be further investigated.

Fire simulator exposure alters the innate epithelial response and inflammatory status in the airways of firefighters.

BACKGROUND: Firefighters are often exposed to high temperatures and by-products of combustion, which can compromise their health. We aimed to evaluate the effect of fire exposure in fire simulators on the airways of firefighters at different time-points. METHODOLOGY: Thirty-seven male firefighters exposed to fire simulators were evaluated in three phases: pre-exposure, at the end of the first week, and 4 weeks after. Pulmonary function by spirometry, nasal mucociliary clearance; peripheral oxygen saturation, inflammatory markers in the nasal lavage and CC16 in the sputum, nasal obstruction, and quality of life (using the questionnaires NOSE and SNOT-22) were assessed. RESULTS: Higher levels of IL-8, IL-10, and exhaled carbon monoxide were found more in phase 2 than in phase 1. Higher CC16 levels and lower peripheral oxygen saturation were observed in phase 3 as compared to phase 1. Lower levels of IL-2 and peripheral oxygen saturation were found in phase 3 than in phase 2. Higher nasal mucociliary clearance, as well as the worst quality of life and nasal obstruction, were observed in phases 2 and 3 as compared to phase 1. CONCLUSIONS: The firefighters’ exposures to high temperatures and by-products of combustion in the fire simulators elicit an inflammatory process in the airways with impairment in the innate epithelial response of the upper airway lining. Furthermore, changes in O2 transport affected the professionals’ quality of life negatively.

Oxidative stress and regulated cell death in Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Motor deficits usually associated with PD correlate with dopaminergic axonal neurodegeneration starting at the striatum, which is then followed by dopaminergic neuronal death in the substantia nigra pars compacta (SN), with both events occurring already at the prodromal stage. We will overview the main physiological characteristics responsible for the higher susceptibility of the nigrostriatal circuit to mitochondrial dysfunction and oxidative stress, as hinted by the acting mechanisms of the PD-causing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Then, we will present multiple lines of evidence linking several cell death mechanisms involving mitochondria and production of reactive oxygen species to neuronal loss in PD, namely intrinsic and extrinsic apoptosis, necroptosis, ferroptosis, parthanatos and mitochondrial permeability transition-driven necrosis. We will focus on gathered data from postmortem PD samples and relevant in vivo models, especially MPTP-based models.

Effective production of multifunctional magnetic-sensitive biomaterial by an extrusion-based additive manufacturing technique.

A calcium phosphate (CaP)-based scaffold used as synthetic bone grafts, which smartly combines precise dimensions, controlled porosity and therapeutic functions, presents benefits beyond those offered by conventional practices, although its fabrication is still a challenge. The sintering step normally required to improve the strength of the ceramic scaffolds precludes the addition of any biomolecules or functional particles before this stage. This study presents a proof of concept of multifunctional CaP-based scaffolds, fabricated by additive manufacturing from an innovative ink composition, with potential for bone regeneration, cancer treatment by local magnetic hyperthermia and drug delivery platforms. Highly loaded inks comprising iron-doped hydroxyapatite and ß-tricalcium phosphate powders suspended in a chitosan-based solution, in the presence of levofloxacin (LEV) as model drug and magnetic nanoparticles (MNP), were developed. The sintering step was removed from the production process, and the integrity of the printed scaffolds was assured by the polymerization capacity of the ink composite, using genipin as a crosslinking agent. The effects of MNP and LEV on the inks' rheological properties, as well as on the mechanical and structural behaviour of non-doped and iron-doped scaffolds, were evaluated. Magnetic and magneto-thermal response, drug delivery and biological performance, such as cell proliferation in the absence and presence of an applied magnetic field, were also assessed. The addition of a constant amount of MNP in the iron-doped and non-doped CaP-based inks enhances their magnetic response and induction heating, with these effects more pronounced for the iron-doped CaP-based ink. These results suggest a synergistic effect between the iron-doped CaP-based powders and the MNP due to ferro/ferrimagnetic interactions. Furthermore, the iron presence enhances human mesenchymal stem cell metabolic activity and proliferation.

TNF-α inhibition decreases MMP-2 activity, reactive oxygen species formation and improves hypertensive vascular hypertrophy independent of its effects on blood pressure.

Systemic arterial hypertension is a public health problem associated with an increased risk of cardiovascular disease. Matrix metalloproteinases (MMP) are endopeptidases that participate in hypertension-induced cardiovascular remodeling, which may be activated by oxidative stress. Angiotensin II (Ang II), a potent hypertrophic and vasoconstrictor peptide, increases oxidative stress, MMP-2 activity and tumor necrosis factor (TNF-α) expression. In vitro studies have shown that TNF-α is essential for Ang II-induced MMP-2 expression. Thus, this study evaluated whetherTNF-α inhibition decreases the development of hypertension-induced vascular remodeling via reduction of MMP-2 activity and reactive oxygen species (ROS) formation. Two distinct pharmacological approaches were used in the present study: Pentoxifylline (PTX), a non-selective inhibitor of phosphodiesterases that exerts anti- inflammatory effects via inhibition of TNF-α, and Etanercept (ETN), a selective TNF-α inhibitor. 2-kidney and 1-Clip (2K1C). 2-kidney and 1-Clip (2K1C) and Sham rats were treated with Vehicle, PTX (50 mg/Kg and 100 mg/kg daily) or ETN (0.3 mg/Kg and 1 mg/kg; three times per week). Systolic blood pressure (SBP) was measured weekly by tail cuff plethysmography. Plasma TNF-α and IL-1ß levels were evaluated by enzyme-linked immunosorbent assay (ELISA) technique. The vascular hypertrophy was examined in the aorta sections stained with hematoxylin/eosin. ROS in aortas was evaluated by dihydroethidium and chemiluminescence lucigenin assay. Aortic MMP-2 levels and activity were evaluated by gel zymography and in situ zymography, respectively. The 2K1C animals showed a progressive increase in SBP levels and was accompanied by significant vascular hypertrophy (p < 0.05 vs Sham). Treatment with PTX at higher doses decreased SBP and vascular remodeling in 2K1C animals (p < 0.05 vs 2K1C vehicle). Although the highest dose of ETN treatment did not reduce blood pressure, the vascular hypertrophy was significantly attenuated in 2K1C animals treated with ETN1 (p < 0.05). The increased cytokine levels and ROS formation were reversed by the highest doses of both PTX and ETN. The increase in MMP-2 levels and activity in 2K1C animals were reduced by PTX100 and ETN1 treatments (p < 0.05 vs vehicle 2K1C). Lower doses of PTX and ETN did not affect any of the evaluated parameters in this study, except for a small reduction in TNF-α levels. The findings of the present study suggest that PTX and ETN treatment exerts immunomodulatory effects, blunted excessive ROS formation, and decreased renovascular hypertension-induced MMP-2 up-regulation, leading to improvement ofvascular remodeling typically found in 2K1C hypertension. Therefore, strategies using anti-hypertensive drugs in combination with TNF alpha inhibitors could be an attractive therapeutic approach to tackle hypertension and its associated vascular remodeling.

Chronic Chikungunya Arthritis and Rheumatoid Arthritis: What They Have in Common.

Chikungunya virus (CHIKV) is a single-stranded RNA virus belonging to the family Togaviridae and genus Alphavirus that causes an acute febrile illness, chikungunya fever, which is transmitted to humans by Aedes species mosquitoes. During acute illness, patients have high fever, polyarthralgias or polyarthritis, maculopapular rash, headache, and myalgia that lasts for days to weeks. Following resolution of acute infection, a significant proportion of patients develop chronic chikungunya arthritis that can resemble rheumatoid arthritis. In this review, we first consider the historical background of infectious causes of inflammatory arthritis, and then the pathogenic and clinical manifestations of chronic chikungunya arthritis as a rheumatoid arthritis mimic. We believe that chronic chikungunya arthritis may be a postinfectious inflammatory process, and that an understanding of the parallels and differences between chronic chikungunya arthritis and rheumatoid arthritis may offer insights into better diagnosis and treatment of both diseases.

Brief report: the disability of chronic chikungunya arthritis.

In 50% of patients, chikungunya fever (CHIKF) is followed by arthritic pain that is often chronic, painful, and disabling. To better define the spectrum of pain and disability in chronic CHIK arthritis (CCA), we evaluated 35 consecutive CCA patients seen in a Brazilian rheumatology clinic, using a pain Visual Analog Scale and the Health Assessment Questionnaire Disability Index. In our patients, pain and disability levels were of the same magnitude as are seen in other serious rheumatic diseases. The mean score for 19 patients with moderate disability was 1.42± 0.20 (median 1.37). The median HAQ-DI score for the entire group was 1.25. These findings underscore the morbidity imposed by CCA and the urgent need for improvements in management.

The Clinical Features, Pathogenesis and Methotrexate Therapy of Chronic Chikungunya Arthritis.

Chikungunya fever (CHIKF) is an emerging viral infection that has spread widely, along with its Aedes vectors, throughout the tropics and beyond, causing explosive epidemics of acute illness and persistent disabling arthritis. The rheumatic symptoms associated with chikungunya virus (CHIKV) infection include polyarthralgia, polyarthritis, morning stiffness, joint edema, and erythema. Chronic CHIK arthritis (CCA) often causes severe pain and associated disability. The pathogenesis of CCA is not well understood. Proposed hypotheses include the persistence of a low level of replicating virus in the joints, the persistence of viral RNA in the synovium, and the induction of autoimmunity. In this review, we describe the main hypotheses of CCA pathogenesis, some of which support methotrexate (MTX) treatment which has been shown to be effective in preliminary studies in CCA.

Treatment of Chronic Chikungunya Arthritis With Methotrexate: A Systematic Review.

OBJECTIVE: Chikungunya virus infection is a rapidly emerging global viral infection that can cause chronic, debilitating arthritis that in some ways mimics rheumatoid arthritis. The aim of this study was to evaluate the available evidence regarding the efficacy and safety of methotrexate (MTX), a therapy that is widely used in rheumatoid arthritis, for the treatment of chronic chikungunya arthritis. METHODS: A systematic literature search was performed to identify all published trials that evaluated MTX as monotherapy or combination therapy in patients with chronic chikungunya arthritis. PubMed, SciELO, Scopus, and Cochrane Library databases were searched from study inception to August 2017. We also searched Google Scholar, the International Clinical Trials Registry Platform Search Portal, and clinicaltrials.gov. RESULTS: Among 131 possibly relevant studies, 6 met our criteria for evaluation: 4 were retrospective studies, 1 was a non-controlled prospective study, and 1 was an unblinded randomized clinical trial of combination MTX therapy. In the randomized clinical trial, triple therapy with MTX, hydroxychloroquine, and sulfasalazine was superior to hydroxychloroquine monotherapy, as assessed by the mean ± SD Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (3.39 ± 0.87 versus 4.74 ± 0.65; P < 0.0001) and the Health Assessment Questionnaire score (1.14 ± 0.31 versus 1.88 ± 0.47; P < 0.0001). CONCLUSION: The number of available studies is limited, but taken together, these studies demonstrate that MTX is sufficiently efficacious to justify further study of MTX for the treatment of chronic chikungunya arthritis. The trials lacked rigorous study designs and used different treatment strategies and outcome measures. This systematic review underscores the need for randomized, prospective, placebo-controlled studies of MTX monotherapy for the treatment of chronic chikungunya arthritis.