An Uncommon Presentation of Secondary Syphilis.

Syphilis is a chronic venereal disease caused by Treponema pallidum (TP). Destructive arthritis is rare in its primary and secondary stages but can occur in the tertiary stage and its congenital form.

Severe infections in Portuguese patients with rheumatoid arthritis under biologic treatment - a multicenter, nationwide study (SIPPRA-B Study).

INTRODUCTION: Despite years of experience with biological disease modifying anti-rheumatic drugs (bDMARD) in rheumatoid arthritis (RA), little is known about differences in infectious risk among bDMARDs. The aim of this study was to assess the incidence and type of infections in RA patients on bDMARDs and to determine possible predictors. METHODS: A retrospective multicenter cohort study that included patients registered in the Rheumatic Diseases Portuguese Registry (Reuma.pt) with RA, and exposed to at least one bDMARD until April 2021. RA patients under bDMARD and with at least one episode of severe infection (SI), defined as infection that requires hospitalization, use of parenteral antibiotics or that resulted in death, were compared to patients with no report of SI. Demographic and clinical data at baseline and at the time of each SI were collected to establish comparisons between different groups of bDMARDs. Comparisons between different bDMARDs were assessed and logistic regression was performed to identify predictors of SI. RESULTS: We included 3394 patients, 2833 (83.5%) female, with a mean age at RA diagnosis of 45.5±13.7 years. SI was diagnosed in 142 of the 3394 patients evaluated (4.2%), totaling 151 episodes of SI. At baseline, patients with SI had a significantly higher proportion of prior orthopedic surgery, asthma, interstitial lung disease, chronic kidney disease and corticosteroid use, higher mean age and longer median disease duration at first bDMARD. Nine patients died (6.0%). Ninety-two SI (60.9%) occurred with the first bDMARD, the majority leading to discontinuation of the bDMARD within 6 months (n=75, 49.7%), while 65 (43.0%) restarted the same bDMARD and 11 (7.3%) switched to another bDMARD (6 of them to a different mechanism of action). In the multivariate analysis, we found that chronic kidney disease, asthma, infliximab, corticosteroid use, interstitial lung disease, previous orthopedic surgery, higher Health Assessment Questionnaire and DAS284V-ESR are independent predictors of SI. CONCLUSION: This study described the incidence and types of SI among Portuguese RA patients on biologics, identifying several predictors of SI, both globally and with different bDMARDs. Physicians should be aware of the real-word infectious risk in RA patients on bDMARDs when making treatment decisions.

Tuberculous Osteomyelitis of The Pubic Symphysis - a Case Report of a Rare Entity Mimicking Spondyloarthritis.

Tuberculosis (TB) osteomyelitis of the pubic symphysis is an extremely rare diagnosis. Axial spondyloarthritis (SpA) is characterized by inflammatory back pain and enthesitis, and involvement of pubic symphysis is very unusual at presentation. A 36-year-old female patient with a history of inflammatory back and pubic pain was referred to Rheumatology. She had a pelvic magnetic resonance imaging (MRI) suggestive of osteitis pubis. She was started on etoricoxib 90mg/day as axial spondyloarthritis was suspected, with no improvement. Pelvic MRI was repeated and showed osteomyelitis of the iliopubic branches. An ultrasound-guided biopsy was performed, and culture was positive for Mycobacterium tuberculosis. Further imaging studies revealed small cavitations and several centrilobular micronodules with a tree-in-bud pattern in the upper lung lobes and in the upper segment of the lower left lobe. She was started on anti-tuberculous treatment for 1 year and had a good clinical and radiological response. TB osteomyelitis of the pubic symphysis is a rare entity and has seldom been reported. However, this is the first case, to our knowledge, where the clinical picture mimicked an itself unusual presentation of SpA.

Oculomotor nerve palsy, an unusual onset of polyarteritis nodosa.

Introduction: Cranial nerve involvement in polyarteritis nodosa(PAN) is underrecognized and rarely reported. The aim of this article is to review the available literature and present an example of oculomotor nerve palsy in the course of PAN. Material and methods: Evaluation of texts describing the analyzed problem using the terms "polyarteritis nodosa", "nerve", "oculomotor", "cranial nerve" and "cranial neuropathy" for searching the PubMed database was done. Only full-text articles in English language with titles and abstracts were included in the analysis. As a guideline for the analysis of articles, the methodology described in the Principles of Individual Patient Data systematic reviews (PRISMA-IPD) was used. Results: After screening articles only 16 reported cases of PAN with cranial neuropathy were included in the analysis. In 10 the cranial neuropathy was reported as the initial manifestation of PAN with optic nerve involvement as the most frequent (62.5%); among these cases the oculomotor nerve was involved in 3 cases. Treatment with glucocorticosteroids and cyclophosphamide was the most common. Conclusions: Although cranial neuropathy, especially oculomotor nerve palsy is a rare first neurological manifestation of PAN, this clinical problem should be considered in the differential diagnosis.Especially patients with peripheral neuropathy, general symptoms, skin lesions and hepatitis B virus infection should be evaluated for cranial nerve involvement in the course of vasculitis.In the case of unclear involvement of the cranial nerves, PAN should also be considered in the differential diagnosis as the cause of symptoms and the first manifestation of the disease.

SARS-CoV-2 variants induce distinct disease and impact in the bone marrow and thymus of mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved to variants associated with milder disease. We employed the k18-hACE2 mouse model to study how differences in the course of infection by SARS-CoV-2 variants alpha, delta, and omicron relate to tissue pathology and the immune response triggered. We documented a variant-specific pattern of infection severity, inducing discrete lung and blood immune responses and differentially impacting primary lymphoid organs. Infections with variants alpha and delta promoted bone marrow (BM) emergency myelopoiesis, with blood and lung neutrophilia. The defects in the BM hematopoietic compartment extended to the thymus, with the infection by the alpha variant provoking a marked thymic atrophy. Importantly, the changes in the immune responses correlated with the severity of infection. Our study provides a comprehensive platform to investigate the modulation of disease by SARS-CoV-2 variants and underscores the impact of this infection on the function of primary lymphoid organs.

Possible relationship between hydroxychloroquine and electrocardiographic and echocardiographic abnormalities in patients with inflammatory rheumatic diseases--a monocentric study.

OBJECTIVE: Hydroxychloroquine (HCQ) is used in the treatment of inflammatory rheumatic diseases and is considered a safe drug. The role of HCQ in the COVID-19 pandemic highlighted some deleterious cardiac effects of HCQ. We aim to evaluate the prevalence and development of cardiac-adverse events in HCQ-treated patients with inflammatory rheumatic diseases. METHODS: We performed a cross-sectional study where patients aged ≥18 years with a diagnosis of inflammatory rheumatic disease currently exposed or not to hydroxychloroquine underwent electrocardiogram (ECG) and echocardiogram. Comparisons between groups were evaluated using chi-square, t test, and Mann-Whitney U test. Logistic regression was performed to determine predictors of changes in ECG and echocardiography. RESULTS: Eighty patients were included, 75 (93.8%) female, aged 52 ± 13 years. ECG changes were seen in higher proportion in patients with hypertension (40.6% vs 12.5%, p = .004) and higher median potassium levels-4.5 (4.1-4.8) versus 4.2 (4.0-4.4), p = .023. Echocardiography changes were seen in older patients (59 ± 11 vs 50 ± 13 years, p = .003) and in patients with higher cumulative dose-1752 (785-2190) versus 438 (328-1022) g, p = 0.008 - and time of exposure to HCQ - 12 (6-15) versus 4 (2-9) years, p = 0.028. HCQ cumulative dose (OR 1.001, CI95% 1.000-1.002, p = .033) and exposure time (OR 1.136, CI95% 1.000-1.289, p = .049) were predictors of echocardiography changes, but when adjusted for age, neither HCQ cumulative dose nor exposure time were predictors of echocardiography changes. CONCLUSION: No association was found between changes in ECG and echocardiogram in patients under HCQ, which remains a safe drug in patients with inflammatory rheumatic diseases.

IoT Sensing Platform as a Driver for Digital Farming in Rural Africa.

Small-scale farming can benefit from the usage of information and communication technology (ICT) to improve crop and soil management and increase yield. However, in order to introduce digital farming in rural areas, related ICT solutions must be viable, seamless and easy to use, since most farmers are not acquainted with technology. With that in mind, this paper proposes an Internet of Things (IoT) sensing platform that provides information on the state of the soil and surrounding environment in terms of pH, moisture, texture, colour, air temperature, and light. This platform is coupled with computer vision to further analyze and understand soil characteristics. Moreover, the platform hardware is housed in a specifically designed robust casing to allow easy assembly, transport, and protection from the deployment environment. To achieve requirements of usability and reproducibility, the architecture of the IoT sensing platform is based on low-cost, off-the-shelf hardware and software modularity, following a do-it-yourself approach and supporting further extension. In-lab validations of the platform were carried out to finetune its components, showing the platform's potential for application in rural areas by introducing digital farming to small-scale farmers, and help them delivering better produce and increasing income.

Reuma.pt/vasculitis - the Portuguese vasculitis registry.

BACKGROUND: The vasculitides are a group of rare diseases with different manifestations and outcomes. New therapeutic options have led to the need for long-term registries. The Rheumatic Diseases Portuguese Register, Reuma.pt, is a web-based electronic clinical record, created in 2008, which currently includes specific modules for 12 diseases and > 20,000 patients registered from 79 rheumatology centres. On October 2014, a dedicated module for vasculitis was created as part of the European Vasculitis Society collaborative network, enabling prospective collection and central storage of encrypted data from patients with this condition. All Portuguese rheumatology centres were invited to participate. Data regarding demographics, diagnosis, classification criteria, assessment tools, and treatment were collected. We aim to describe the structure of Reuma.pt/vasculitis and characterize the patients registered since its development. RESULTS: A total of 687 patients, with 1945 visits, from 13 centres were registered; mean age was 53.4 ± 19.3 years at last visit and 68.7% were females. The most common diagnoses were Behçet's disease (BD) (42.5%) and giant cell arteritis (GCA) (17.8%). Patients with BD met the International Study Group criteria and the International Criteria for BD in 85.3 and 97.2% of cases, respectively. Within the most common small- and medium-vessel vasculitides registered, median [interquartile range] Birmingham Vasculitis Activity Score (BVAS) at first visit was highest in patients with ANCA-associated vasculitis (AAV) (17.0 [12.0]); there were no differences in the proportion of patients with AAV or polyarteritis nodosa who relapsed (BVAS≥1) or had a major relapse (≥1 major BVAS item) during prospective assessment (p = 1.00, p = 0.479). Biologic treatment was prescribed in 0.8% of patients with GCA, 26.7% of patients with AAV, and 7.6% of patients with BD. There were 34 (4.9%) deaths reported. CONCLUSIONS: Reuma.pt/vasculitis is a bespoke web-based registry adapted for routine care of patients with this form of rare and complex diseases, allowing an efficient data-repository at a national level with the potential to link with other international databases. It facilitates research, trials recruitment, service planning and benchmarking.

Siboglinidae Tubes as an Additional Niche for Microbial Communities in the Gulf of Cádiz-A Microscopical Appraisal.

Siboglinids were sampled from four mud volcanoes in the Gulf of Cádiz (El Cid MV, Bonjardim MV, Al Gacel MV, and Anastasya MV). These invertebrates are characteristic to cold seeps and are known to host chemosynthetic endosymbionts in a dedicated trophosome organ. However, little is known about their tube as a potential niche for other microorganisms. Analyses by scanning and transmission electron microscopy showed dense biofilms on the tube in Al Gacel MV and Anastasya MV specimens by prokaryotic cells. Methanotrophic bacteria were the most abundant forming these biofilms as further supported by 16S rRNA sequence analysis. Furthermore, elemental analyses with electron microscopy and energy-dispersive X-ray spectroscopy point to the mineralization and silicification of the tube, most likely induced by the microbial metabolisms. Bacterial and archaeal 16S rRNA sequence libraries revealed abundant microorganisms related to these siboglinid specimens and certain variations in microbial communities among samples. Thus, the tube remarkably increases the microbial biomass related to the worms and provides an additional microbial niche in deep-sea ecosystems.

Comparative outcome assessment of epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of advanced non-small-cell lung cancer: a network meta-analysis.

Introduction: Tyrosine kinase inhibition of the epidermal growth factor receptor (EGFR) is the standard in the first line treatment of patients with advanced non-small-cell lung cancer (NSCLC) harbouring EGFR activating mutations. Here we aim to discern efficacy and toxicity measures through a meta-analysis of published studies that could aid treatment selection. Materials And Methods: We performed a meta-analysis of the main randomized clinical trials evaluating the currently approved EGFR-TKIs in first-line of treatment of EGFR-positive advanced NSCLC. Cochrane guidelines were used for statistical analysis. Results: 3,179 patients were included. All EGFR TKIs showed improved outcomes with respect to ORR and PFS when compared to standard platinum-doublet chemotherapy. Comparative ORR for gefitinib, erlotinib and afatinib were 52.1%, 67.3% and 61.6% respectively. HRs for PFS were 0.62 (95% CI, 0.38-1.00) for gefitinib, 0.28 (95% CI, 0.17-0.45) for erlotinib and 0.40 (95% CI, 0.20-0.83) for afatinib. HRs for OS were not statistically significant for any agent. Conclusions: Our results suggest similar clinical efficacy and higher toxicity of Afatinib treatment. As this still remains the agent with best CSF penetration, we suggest its use is limited to patients presenting with brain metastasis. We suggest the use of Gefitinib in patients without CNS involvement. Faced with the impossibility to dose-reduce Gefitinib, Erlotinib represents a tolerable and effective alternative to Afatinib and Gefitinib if response to EGFR inhibition is considered still effective.

Structural polymeric features that contribute to in vitro immunostimulatory activity of instant coffee.

An instant coffee fraction, rich in arabinogalactans, obtained by ultrafiltration, using 1 and 5kDa membranes, has previously shown in vitro stimulatory activity on BALB/c mice spleen B lymphocytes. The compounds inducing lymphocytic activation were shown to elute, mainly near the void volume by size-exclusion chromatography, using Bio-Gel P6 (1-6kDa). Treatment of the compounds with chymotrypsin, a digestive protease, did not affect the induced B lymphocyte activation. On the contrary, hydrolysis with an α-l-arabinofuranosidase, removing single terminally-linked arabinose residues, decreased the extent of B cell activation. The immunostimulatory activity of these compounds was also observed by in vitro experiments, using bone marrow-derived macrophages and dendritic cells as responders. Altogether, these results show the relevance of single arabinose residues, present at the non-reducing end of polymeric compounds, to the coffee stimulatory activity in cells mediating innate and acquired immunity.

Silent acute myocarditis in eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis is a rare multisystemic disorder, characterized by necrotizing vasculitis affecting small to medium-sized vessels, associated with asthma and eosinophilia. Cardiac involvement is the most important predictor of mortality and it seems to be more frequent in anti-neutrophil cytoplasmic antibodies-negative patients. Cardiomyopathy and congestive heart failure can occur but a significant proportion of patients are asymptomatic. We present a case of this condition in a 65-year-old woman with a past medical history of rhinosinusitis and recent episodes of asthma, that developed palpable purpura, sensory deficiency and excruciating pain mainly in the lower limbs. A significant hypereosinophilia and elevated troponin level were found, although she had not cardiac symptomatology. Cardiovascular magnetic resonance revealed late gadolinium enhancement and a severe reduction of the left ventricular ejection fraction. Mononeuritis multiplex was documented and diagnosis was confirmed by biopsy. Complementary cardiac investigation is mandatory in any patient with suspicion of Eosinophilic granulomatosis with polyangiitis. Early detection and the appropriate treatment are crucial due to the possible life-threatening manifestations.

Sarcoidosis: an unusual presentation / Sarcoidosis: un cuadro clínico inicial poco frecuente

A 35-year-old man presented with a 3-year history of arthralgia and purple coloration of the skin of his fingers and feet. Hand and foot radiography showed cystic bone lesions on phalanges suggestive of sarcoidosis. Lab tests revealed increased liver enzymes. Liver MRI evidenced an enlarged liver and retroperitoneal lymphadenopathy. Histological analysis of the finger skin, lymph nodes and liver demonstrated the presence of granulomas, confirming the diagnosis of sarcoidosis. The patient started prednisolone with rapid improvement of the symptoms. Skin lesions are divided into two groups: specific for sarcoidosis (with granulomas, lupus pernio-like) and nonspecific (without granulomas, erythema nodosum-like). Specific cutaneous lesions usually cause no other symptoms beyond cosmetic changes. Lupus pernio stands out for having distinctive features but, to the best of our knowledge, the simultaneous involvement of both hands and feet has never been reported (AU)

Se presenta el caso de un hombre de 35 años con una historia de artralgia y con la piel de los dedos y los pies de color violáceo, de 3 años de duración. La radiografía de pies y manos mostró lesiones quísticas óseas en las falanges, indicativas de sarcoidosis. Las pruebas de laboratorio revelaron una elevación de las enzimas hepáticas. La resonancia magnética hepática puso de manifiesto hepatomegalia y linfadenopatía retroperitoneal. El análisis histológico de la piel de los dedos, los ganglios linfáticos y el hígado mostró la existencia de granulomas, lo que confirmó el diagnóstico de sarcoidosis. El paciente comenzó el tratamiento con prednisolona con una rápida mejoría de los síntomas. Las lesiones de la piel se dividen en 2 grupos: específicas de la sarcoidosis (con granulomas y lupus característico del eritema pernio) e inespecíficas (sin granulomas y de tipo eritema nudoso). Las lesiones cutáneas específicas generalmente no causan más síntomas que los cambios estéticos. El lupus pernio destaca por presentar características distintivas, pero no nos consta que se haya descrito nunca la afectación simultánea de ambas manos y pies (AU)