Assessment of hydroxychloroquine blood levels in Sjögren's disease patients: drug adherence and clinical associations.

Hydroxychloroquine (HCQ) has been used to treat Sjögren's disease (SjD) patients. However, there are no studies evaluating drug adherence through HCQ blood levels, pharmacy refill (PR) and medication adherence questionnaires. The relationship of HCQ blood levels with glandular/extraglandular disease parameters was also poorly assessed. This cross-sectional observational study included 74 adult SjD patients, who were receiving a stable HCQ dose (4-5.5 mg/kg/day, actual weight) for at least 3 months before study inclusion. HCQ blood levels were quantified by high-performance liquid chromatography coupled to mass spectrometry. Adherence was assessed by PR and Medida de Adesão aos Tratamentos (MAT) questionnaire. The following parameters were evaluated: Xerostomia Inventory, Ocular Surface Disease Index, EULAR (European League Against Rheumatism) Sjögren's Syndrome Disease Activity Index, EULAR Sjögren's Syndrome Patient Reported Index, Schirmer's I test and non-stimulated/stimulated salivary flow rates. HCQ blood levels were 775.3(25.0-2,568.6)ng/mL. Eleven patients (14.9%) had HCQ blood levels < 200ng/mL (non-adherent group); 11(14.9%), 200-499ng/mL (sub-therapeutic levels group); and 52(70.2%), ≥ 500ng/mL (adherent group). PR classified incorrectly all non-adherent/sub-therapeutic patients and 2/52(3.9%) adherent patients. Using MAT, the overall misclassification was 24/52(46.2%) in the adherent group, and were correctly identified 9/11(81.8%) patients in non-adherent and 7/11(63.6%) in sub-therapeutic groups. MAT sensitivity and specificity to identify non-adherent/sub-therapeutic patients were 72.7% and 53.9%, respectively. The three groups were comparable regarding glandular/extraglandular disease parameters (p > 0.05). The assessment of HCQ blood levels is a promising tool for evaluating drug adherence in SjD. This is particularly crucial as one-third of patients exhibited non-adherence/sub-therapeutic levels, and neither PR nor MAT reliably identified these patients.

Acaricidal activity of a 2-methoxy-clovan-9-ol rich fraction from Eugenia copacabanensis (Myrtaceae) extract on Rhipicephalus microplus (Acari: Ixodidae).

Rhipicephalus microplus (Ixodidae, canestrini, 1888) is an invasive ectoparasite of cattle which causes high economic losses in emerging countries such as Brazil. Phytochemical compounds have been tested as an alternative to synthetic acaricides due to potentially lower mammalian toxicity. This study evaluated the acaricidal activity against R. microplus of the 2-methoxy-clovan-9-ol rich fraction obtained from Eugenia copacabanensis Kiaersk.leaves, a little known Myrtaceae species from the Brazilian Atlantic Forest. This fraction was obtained by maceration with methanol, partition with n-hexane and purification by normal-phase column chromatography. GC-MS, 1H and 13C NMR and IR analysis contributed to the identification of a major compound as the sesquiterpene 2-methoxy-clovan-9-ol, reported for the first time for the Myrtaceae family. The fraction was tested against R. microplus unfed larvae and engorged females and a 93% larval mortality was observed at the concentration of 50 mg mL-1. Lower concentrations of the solution tested demonstrated a significant difference in egg mass weight, hatching and control percentage. Experiments with 50.0 mg mL-1 showed significative results, with lower concentration and maximum efficacy for both assays. The IC50 values for unfed larvae and engorged females were 21.76 and 11.13 mg mL-1, respectively. These results were similar to those obtained in other studies with isolated botanical compounds and essential oils. The lower IC50 for engorged females than for unfed R. microplus larvae had also been described for other plant materials, including plants from the same Myrtaceae family. The present result suggested different mechanisms of action of the compound on the reproductive biology of engorged females, improving its effect against egg viability. These results are important for tick control, suggesting that 2-methoxy-clovan-9-ol could be a potential natural acaricidal product against both R. microplus unfed larvae and engorged females.

Robust immunogenicity to the H3N2 component of influenza A vaccine in primary Sjögren syndrome.

INTRODUCTION: Influenza A (H3N2) virus is the major cause of morbidity/mortality due to seasonal influenza over 50 years. Data about the safety/immunogenicity of influenza A/Singapore (H3N2) vaccine are scarce in primary Sjögren syndrome (pSS). METHODS: Twenty-one consecutive pSS patients and 42 HC (healthy control individuals) were immunized with influenza A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus. Rates of SP (seroprotection) and SC (seroconversion), GMT (geometric mean titers), FI-GMT (factor increase in GMT), ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index), and adverse events were appraised before and 4 weeks post-vaccination. RESULTS: pSS and HC had similar mean age (51.2 ± 14.2 vs. 50.6 ± 12.1 years, p = 0.886). Pre-vaccination SP rates were high in pSS and HC (90.5% vs. 71.4%, p = 0.114), and GMT were higher in pSS [80.0 (52.4-160.0) vs. 40.0 (20.0-80.0), p = 0.001]. The percentage of influenza vaccination in the preceding two years was elevated and similar in pSS and HC (94.1% vs. 94.6%, p = 1.000). GMT values augmented in both groups four weeks after vaccination and persisted higher in the first group [160.0 (80.0-320.0) vs. 80.0 (40.0-80.0), p < 0.001] with equivalent FI-GMT [1.4 (1.0-2.8) vs. 1.4 (1.0-2.0), p = 0.410]. Both groups had low and similar SC rates (19.0% vs. 9.5%, p = 0.423). ESSDAI values persisted steadily during the study (p = 0.313). No serious adverse events have occurred. CONCLUSION: The novel demonstration that the influenza A/Singapore (H3N2) vaccine induces a different pattern of immunogenicity from other influenza A constituents in pSS, featured by a desirable high pre- and post-vaccination immunogenicity, is in line with reported differences in immune responses between strains in trivalent vaccines and may be related to pre-existing immunity. CLINICALTRIALS: gov: #NCT03540823. Key Points • This prospective study demonstrated a robust pre- and post-vaccination immunogenicity to influenza A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus in primary Sjögren's syndrome (pSS). • This high immunogenicity pattern may be related to pre-existing immunization, or else it is related to immunogenicity differences of each strain. • This vaccine had an adequate safety profile in pSS, with no impact on disease activity.

Post-acute COVID-19 in three doses vaccinated autoimmune rheumatic diseases patients: frequency and pattern of this condition.

BACKGROUND: Data on post-acute COVID-19 in autoimmune rheumatic diseases (ARD) are scarce, focusing on a single disease, with variable definitions of this condition and time of vaccination. The aim of this study was to evaluate the frequency and pattern of post-acute COVID-19 in vaccinated patients with ARD using established diagnosis criteria. METHODS: Retrospective evaluation of a prospective cohort of 108 ARD patients and 32 non-ARD controls, diagnosed with SARS-CoV-2 infection (RT-PCR/antigen test) after the third dose of the CoronaVac vaccine. Post-acute COVID-19 (≥ 4 weeks and > 12 weeks of SARS-CoV-2 symptoms) were registered according to the established international criteria. RESULTS: ARD patients and non-ARD controls, balanced for age and sex, had high and comparable frequencies of ≥ 4 weeks post-acute COVID-19 (58.3% vs. 53.1%, p = 0.6854) and > 12 weeks post-acute COVID-19 (39.8% vs. 46.9%, p = 0.5419). Regarding ≥ 4 weeks post-acute COVID-19, frequencies of ≥ 3 symptoms were similar in ARD and non-ARD controls (54% vs. 41.2%, p = 0.7886), and this was also similar in > 12 weeks post-acute COVID-19 (68.3% vs. 88.2%, p = 0.1322). Further analysis of the risk factors for ≥ 4 weeks post-acute COVID-19 in ARD patients revealed that age, sex, clinical severity of COVID-19, reinfection, and autoimmune diseases were not associated with this condition (p > 0.05). The clinical manifestations of post-acute COVID-19 were similar in both groups (p > 0.05), with fatigue and memory loss being the most frequent manifestations. CONCLUSION: We provide novel data demonstrating that immune/inflammatory ARD disturbances after third dose vaccination do not seem to be a major determinant of post-acute COVID-19 since its pattern is very similar to that of the general population. Clinical Trials platform (NCT04754698).

Anti-SARS-CoV-2 inactivated vaccine in patients with ANCA-associated vasculitis: Immunogenicity, safety, antibody decay and the booster dose.

OBJECTIVE: To evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients. METHODS: Fifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vaccine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Antibodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240). RESULTS: At D69 SC (65.1% vs. 96.8%, p = 0.0001), GMT (21.3 UA/mL vs. 67.7 UA/mL, p < 0.001) and NAb- positivity (53.7% vs. 80.6%, p = 0.001) were moderate but lower in naïve-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p = 0.015), mycophenolate mofetil (20% vs. 0%, p = 0.037) and prednisone (60.0% vs. 28.6%, p = 0.057) than seroconverted. NAb negativity in AAV patients was associated with prednisone treatment (57.9% vs. 18.2%, p = 0.015) and IS (84.2% vs. 55.0%, p = 0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR = 0.2, 0,95% CI 0.05‒0.86, p = 0.030) and with lower NAb positivity (OR = 0.2, 0,95% CI 0.05‒0.88, p = 0.034). After six months (D69‒D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p = 0.074) and 32 CG (18.7%, p = 0.041). For the NAb positivity, the 6-month decrease was not significant (p = 0.114) whereas a major reduction occurred for CG (p < 0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p = 0.023) and NAb-positivity (34.4%, p = 0.006) in AAV patients. No moderate/severe adverse events attributable to the vaccine were observed. CONCLUSION: This study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698).

Synovial chondromatosis of the temporomandibular joint-clinical, surgical, and imaging findings of a Milgram stage III case series.

Synovial chondromatosis of the temporomandibular joint (TMJ) is a rare disease characterized by cartilaginous metaplasia of the mesenchymal remnants of the synovial membrane with formation of loose cartilaginous nodules. It is prevalent in middle-aged women and the main clinical characteristics are swelling, pain, and limited jaw movements. Diagnosis is difficult, especially in the early stages, because the signs and symptoms are like other TMJ diseases such as internal derangements and tumors. Imaging exams are fundamental in differential diagnosis for detection of synovitis and free cartilaginous bodies. Magnetic resonance imaging with a gadolinium contrast would be of particular interest for this purpose. Treatment involves the removal of the cartilaginous nodules and synovectomy. It can be performed by arthroscopy or arthrotomy depending on the size of the lesion, the number of corpuscles, and the need for auxiliary surgical procedures. Final diagnosis is anatomopathologic. Postoperative follow-up is necessary due to the risk of recurrence.

Effect of low temperature and room temperature on the depth of cure of bulk-fill composite resins

The study analyzed the influence of temperature on the depth of cure of bulk-fill composite resins. Three discs (ISO 4049/2000) from each group were made, and four restorative materials were investigated: Opus Bulk-Fill Flow, Opus Bulk-Fill APS, Filtek™ One Bulk-Fill, and Filtek™ Bulk-Fill Flow. They were light-cured (Gnatus ± 1,200 mW/cm2) for 20 seconds, varying the temperature (23°C and 5°C) and simulating the use of the product both at room temperature and under refrigeration. The materials were inserted in aluminum matrices with 10 mm in depth and 4 mm in diameter. A clear film strip and a glass microscope slide were positioned at the top and bottom surfaces. The material was condensed and light-cured with the tip of the light source in close contact, for 20 seconds on the top surface. Immediately after irradiation, the samples were removed from the mold, and the uncured part was removed with a plastic spatula. The measurement was performed with a micrometer ± 0.1 mm, and the value was divided by 2. The data were analyzed with two-way ANOVA at a significance of 0.05. There was a statistical difference in the temperature between the results obtained in Opus Bulk-Fill APS (p <0.001) and Filtek™ Bulk-Fill Flow (p = 0.018) resins. For the temperature of 5°C, Filtek™ Bulk-Fill Flow showed a statistical difference compared to the other resins, while Opus Bulk-Fill Flow and Opus Bulk-Fill APS did not. For the temperature of 23°C, Filtek™ Bulk-Fill Flow maintained the statistical difference from the others, but Filtek™ One Bulk-Fill and Opus Bulk-Fill APS did not present statistical differences. Storing the Filtek™ Bulk-Fill Flow composite resin in the refrigerator caused a greater depth of cure than the other resins, and the depth of cure decreased at room temperature. As for Opus Bulk-Fill APS, the depth of cure decreased proportionally to the temperature decrease. The temperature may affect the depth of cure of some composite resins.

Anti-SARS-CoV-2 inactivated vaccine in patients with ANCA-associated vasculitis: Immunogenicity, safety, antibody decay and the booster dose

Abstract Objective: To evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients. Methods: Fifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vaccine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Antibodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240). Results: At D69 SC (65.1% vs. 96.8%, p = 0.0001), GMT (21.3 UA/mL vs. 67.7 UA/mL, p < 0.001) and NAb- positivity (53.7% vs. 80.6%, p = 0.001) were moderate but lower in naïve-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p = 0.015), mycophenolate mofetil (20% vs. 0%, p = 0.037) and prednisone (60.0% vs. 28.6%, p = 0.057) than seroconverted. NAb negativity in AAV patients was associated with prednisone treatment (57.9% vs. 18.2%, p = 0.015) and IS (84.2% vs. 55.0%, p = 0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR = 0.2, 0,95% CI 0.05-0.86, p = 0.030) and with lower NAb positivity (OR = 0.2, 0,95% CI 0.05-0.88, p = 0.034). After six months (D69-D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p = 0.074) and 32 CG (18.7%, p = 0.041). For the NAb positivity, the 6-month decrease was not significant (p = 0.114) whereas a major reduction occurred for CG (p < 0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p = 0.023) and NAb-positivity (34.4%, p = 0.006) in AAV patients. No moderate/severe adverse events attributable to the vaccine were observed. Conclusion: This study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698).

Post-acute COVID-19 in three doses vaccinated autoimmune rheumatic diseases patients: frequency and pattern of this condition

Abstract Background Data on post-acute COVID-19 in autoimmune rheumatic diseases (ARD) are scarce, focusing on a single disease, with variable definitions of this condition and time of vaccination. The aim of this study was to evaluate the frequency and pattern of post-acute COVID-19 in vaccinated patients with ARD using established diagnosis criteria. Methods Retrospective evaluation of a prospective cohort of 108 ARD patients and 32 non-ARD controls, diagnosed with SARS-CoV-2 infection (RT-PCR/antigen test) after the third dose of the CoronaVac vaccine. Post-acute COVID-19 (≥ 4 weeks and > 12 weeks of SARS-CoV-2 symptoms) were registered according to the established international criteria. Results ARD patients and non-ARD controls, balanced for age and sex, had high and comparable frequencies of ≥ 4 weeks post-acute COVID-19 (58.3% vs. 53.1%, p = 0.6854) and > 12 weeks post-acute COVID-19 (39.8% vs. 46.9%, p = 0.5419). Regarding ≥ 4 weeks post-acute COVID-19, frequencies of ≥ 3 symptoms were similar in ARD and non-ARD controls (54% vs. 41.2%, p = 0.7886), and this was also similar in > 12 weeks post-acute COVID-19 (68.3% vs. 88.2%, p = 0.1322). Further analysis of the risk factors for ≥ 4 weeks post-acute COVID-19 in ARD patients revealed that age, sex, clinical severity of COVID-19, reinfection, and autoimmune diseases were not associated with this condition (p > 0.05). The clinical manifestations of post-acute COVID-19 were similar in both groups (p > 0.05), with fatigue and memory loss being the most frequent manifestations. Conclusion We provide novel data demonstrating that immune/inflammatory ARD disturbances after third dose vaccination do not seem to be a major determinant of post-acute COVID-19 since its pattern is very similar to that of the general population. Clinical Trials platform (NCT04754698).

Óleos essenciais e extratos vegetais como ferramentas alternativas ao controle químico de larvas de Aedes spp, Anopheles spp e Culex spp / Essential oils and plant extracts as alternative tools for chemical control of Aedes spp, Anopheles spp, and Culex spp

Objetivos: Realizar um levantamento das contribuições científicas produzidas entre 2017 e 2021 acerca do efeito larvicida de óleos essenciais e extratos vegetais no controle de Aedes spp, Anopheles spp e Culex spp. Métodos: de setembro a outubro de 2022, foi realizado um levantamento de artigos científicos publicados entre os anos de 2017 e 2021, nas bases de dados Portal Periódicos Capes, Scielo, Science Direct e Scopus. Foram utilizados os descritores "larvicide", "essential oil" e "plant extracts" com a interposição do operador boleano "AND". Resultados: inicialmente, foram obtidos 246 artigos, dos quais 110 foram excluídos (68 não estavam disponíveis na íntegra e 42 apareceram em mais de uma base de dados). Dos 136 artigos restantes, 36 foram excluídos por não terem realizado ensaio larvicida. Dos 100 artigos remanescentes, 63 foram excluídos por não mencionarem valores de CL50, enquanto 3 não especificaram a estrutura vegetal de obtenção dos produtos naturais, restando, portanto, 34 artigos para análise. Foram utilizadas 57 espécies vegetais para a obtenção dos produtos vegetais utilizados contra larvas de Aedes spp; 11 espécies nos ensaios contra Anopheles spp, e 36 espécies nos ensaios contra Culex spp. Os óleos essenciais predominaram nos ensaios contra Aedes spp, enquanto os extratos, contra Anopheles spp. A maior parte dos produtos testados exibiu CL50 < 100 ppm. Conclusão: a atividade larvicida demonstrada por uma grande variedade de extratos vegetais e óleos essenciais representa uma alternativa promissora ao tradicional controle químico feito à base de inseticidas sintéticos em programas de manejo integrado de vetores.

Objectives: Conduct a survey of the scientific contributions produced between 2017 and 2021 on the larvicidal effect of essential oils and plant extracts in the control of Aedes spp, Anopheles spp, and Culex spp. Methods: from September to October 2022, a survey was carried out of scientific articles published between 2017 and 2021 in the Portal Periódicos Capes, Scielo, Science Direct, and Scopus databases. The descriptors "larvicide", "essential oil" and "plant extracts" were used with the Boolean operator "AND". Results: initially, 246 articles were obtained, of which 110 were excluded (68 were not available, and 42 appeared in more than one database). Of the remaining 136 articles, 36 were excluded because they did not perform a larvicide assay. Of the 100 remaining articles, 63 were excluded for not mentioning LC50 values, while three did not specify the plant structure for obtaining natural products, thus leaving 34 articles for analysis. A total of 57 plant species were used to obtain plant products used against Aedes spp larvae; 11 species in the tests against Anopheles spp, and 36 species in the tests against Culex spp. Essential oils predominated in the tests against Aedes spp, while extracts against Anopheles spp. Most of the products tested exhibited an LC50 < 100 ppm. Conclusion: the larvicidal activity demonstrated by a wide variety of plant extracts and essential oils represents a promising alternative to traditional chemical control based on synthetic insecticides in integrated vector management programs.

Immunogenicity decay and case incidence six months post Sinovac-CoronaVac vaccine in autoimmune rheumatic diseases patients.

The determination of durability and vaccine-associated protection is essential for booster doses strategies, however data on the stability of SARS-CoV-2 immunity are scarce. Here we assess anti-SARS-CoV-2 immunogenicity decay and incident cases six months after the 2nd dose of Sinovac-CoronaVac inactivated vaccine (D210) in 828 autoimmune rheumatic diseases patients compared with 207 age/sex-balanced control individuals. The primary outcome is the presence of anti-S1/S2 SARS-CoV-2 IgG at 6 months compared to 6 weeks after 2nd vaccine dose for decay evaluation. Secondary outcomes are presence of neutralizing antibodies, percent inhibition by neutralizing, geometric mean titers and cumulative incident cases at 6 months after 2nd dose. Anti-S1/S2 IgG positivity and titers reduce to 23.8% and 38% in patients (p < 0.001) during the six-month follow up and 20% and 51% in controls (p < 0.001), respectively. Neutralizing antibodies positivity and percent inhibition declines 41% and 54% in patients (p < 0.001) and 39.7% and 47% in controls (p < 0.001). Multivariate logistic regression analysis show males (OR = 0.56;95% CI0.40-0.79), prednisone (OR = 0.56; 95% CI0.41-0.76), anti-TNF (OR = 0.66;95% CI0.45-0.96), abatacept (OR = 0.29; 95% CI0.15-0.56) and rituximab (OR = 0.32;95% CI0.11-0.90) associate with a substantial reduction in IgG response at day 210 in patients. Although cellular immunity was not assessed, a decrease of COVID-19 cases (from 27.5 to 8.1/100 person-years; p < 0.001) is observed despite the concomitant emergence and spread of the Delta variant. Altogether we show a reduction in immunity 6-months of Sinovac-CoronaVac 2nd dose, particularly in males and those under immunosuppressives therapies, without a concomitant rise in COVID-19 cases. (CoronavRheum clinicaltrials.gov:NCT04754698).

Primary dental care treatment in primary Sjögren's syndrome: a possible role in improving salivary flow rate.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is an inflammatory chronic disorder that mainly affects exocrine glands. Additionally, oral infections can aggravate the glandular dysfunction. However, data on primary dental care (PDC) treatment in pSS are scarce. This study aimed to appraise the impact of PDC on the Xerostomia Inventory (XI), unstimulated/stimulated salivary flow rates and salivary cytokine profile in pSS. METHODS: Fifty-two pSS patients and 52 sex- and age-matched control participants without systemic autoimmune diseases were included in a prospective study. At inclusion, all participants were assessed through a standardised protocol, measurement of salivary pro-inflammatory cytokines, and underwent PDC. Dental procedures included: oral hygiene guidance, restorative treatment of caries, surgical removal of residual roots and impacted or partially erupted teeth, cysts, supra and subgingival periodontal scaling and treatment of soft tissue disorders (removal of lesions and treatment of opportunistic infections). After 3 months, the clinical/laboratorial assessments were repeated. RESULTS: At inclusion, the Decayed, Missing and Filled Teeth (DMFT) index was higher in the pSS patients than in the control group (13.3±8.2 vs. 8.6±6.2, p=0.002), whereas periodontal parameters were comparable in both groups (p>0.05). After PDC, 26.9% of pSS patients showed a reduction of at least 6 points (clinical improvement) in XI, but mean XI remained unchanged (p=0.285). PDC resulted in an increase in mean unstimulated (p<0.001) and stimulated (p=0.001) salivary flow rates in pSS, with no change in salivary cytokine profile (p≥0.05). CONCLUSIONS: PDC promoted improvement in unstimulated and stimulated salivary flow rates in pSS. This novel finding reinforces the recommendation of this strategy for pSS patients. CLINICALTRIALS: gov (Identifier: NCT03711214).

Tuberculous Aortic Pseudoaneurysm: An Unexpected Encounter with an Old Acquaintance.

Introduction: Mycobacterium tuberculosis (MT) is a rare cause of mycotic aneurysms. Diagnosis and management of tuberculous arterial infection is challenging. A case of a patient diagnosed and successfully treated for an aortic pseudoaneurysm caused by MT infection is reported. Report: An 83 year old man was admitted with recurrent back pain over five months associated with constitutional symptoms. Computed tomography angiography (CTA) revealed a psoas collection associated with terminal aorta and proximal left common iliac artery posterolateral wall ulceration. Percutaneous drainage was performed and both the acid fast bacillus test and the molecular test for MT DNA were positive. The patient started on anti-tuberculous treatment, showing an excellent response. Three month CTA revealed arterial ulceration stability. However, the six month CTA revealed evolution to an asymptomatic 40 mm pseudoaneurysm. He was submitted to open repair with an aorto-bi-iliac interposition silver acetate/triclosan collagen coated polyester graft. The post-operative course was uneventful. Discussion: Increased awareness and pursuit of an histological and microbiological diagnosis along with close surveillance allow anticipation of complications that can develop without any warning symptoms, as reported in this case. Agent identification and a combination of prolonged anti-tuberculous drug therapy with extensive excision of the infected field along with aortic reconstruction contributed to a good outcome.

Frequency of lipid-poor adrenal adenomas in magnetic resonance imaging examinations of the abdomen.

Objective: To estimate the frequency of lipid-poor adenomas (LPAs) in magnetic resonance imaging (MRI) examinations. Materials and Methods: We retrospectively investigated adrenal lesions on MRI examinations performed in a total of 2,014 patients between January 2016 and December 2017. After exclusions, the sample comprised 69 patients with 74 proven adenomas. Two readers (reader 1 and reader 2) evaluated lesion size, laterality, homogeneity, signal drop on out-of-phase (OP) images, and the signal intensity index (SII). An LPA was defined as a lesion with no signal drop on OP images and an SII < 16.5%. For 68 lesions, computed tomography (CT) scans (obtained within one year of the MRI) were also reviewed. Results: Of the 69 patients evaluated, 42 (60.8%) were women and 27 (39.2%) were men. The mean age was 59.2 ± 14.1 years. Among the 74 confirmed adrenal adenomas evaluated, the mean lesion size was 18.5 ± 7.7 mm (range, 7.0-56.0 mm) for reader 1 and 21.0 ± 8.3 mm (range, 7.0-55.0 mm) for reader 2 (p = 0.055). On the basis of the signal drop in OP MRI sequences, both readers identified five (6.8%) of the 74 lesions as being LPAs. When determined on the basis of the SII, that frequency was three (4.0%) for reader 1 and four (5.4%) for reader 2. On CT, 21 (30.8%) of the 68 lesions evaluated were classified as LPAs. Conclusion: The prevalence of LPA was significantly lower on MRI than on CT. That prevalence tends to be even lower when the definition of LPA relies on a quantitative analysis rather than on a qualitative (visual) analysis.

Objetivo: Estimar a frequência de adenomas pobres em lipídios (APLs) em exames de ressonância magnética (RM). Materiais e Métodos: Investigaram-se, retrospectivamente, as lesões adrenais em exames de RM realizados de janeiro de 2016 a dezembro de 2017. Um total de 2.014 pacientes foi submetido a exames abdominais e, após exclusões, 69 pacientes com 74 adenomas foram recuperados. Determinaram-se o tamanho da lesão, a lateralidade, a homogeneidade, a queda do sinal em imagens fora-de-fase (FF) e o índice de intensidade do sinal (IIS). Foram utilizadas as seguintes definições para APLs: sem queda de sinal nas imagens FF e IIS < 16,5%. Para 68 lesões, havia imagens de tomografia computadorizada (TC), com intervalo de até um ano da RM, que também foram analisadas. Resultados: Sessenta e nove pacientes foram incluídos, sendo 42 mulheres (60,8%) e 27 homens (39,2%). A média de idade foi 59,2 ± 14,1 anos. O tamanho médio do adenoma adrenal foi 18,5 ± 7,7 mm para o leitor 1 (7,0-56,0 mm) e 21,0 ± 8,3 mm (7,0-55,0 mm) para o leitor 2 (p = 0,055). A queda de sinal nas imagens FF mostrou que a frequência de APLs para ambos os leitores foi 6,8% (5/74). Para a análise quantitativa, a frequência foi 4,0% (3/74) para o leitor 1 e 5,4% (4/74) para o leitor 2. A frequência de APLs nas imagens de TC foi 21/68 lesões (30,8%). Conclusão: A prevalência de APLs em imagens de RM foi significativamente menor do que em exames de TC. Essa prevalência tende a ser ainda menor quando a definição de APL é baseada na análise quantitativa (IIS < 16,5%), em vez da análise visual.

Early versus delayed debridement for surgical site infection after oncological neurosurgery.

Background: There are no guidelines on the management of surgical site infection (SSI) in neurosurgery. This study sought to analyze whether early debridement improved survival compared to antibiotic therapy alone in patients with postcraniotomy infections after oncological neurosurgeries. Methods: We retrospectively reviewed patient records from 2011 to 2019 to identify patients that had been reoperated for the debridement of SSI after brain tumor resection. If SSI was suspected but not clinically evident, the diagnosis was confirmed by cerebrospinal fluid (CSF) analysis or contrast-based imaging examinations. Immediately after diagnosis, broad-spectrum antibiotics were started for all patients. Results: Out of 81 SSI cases, 57 underwent debridement. Two patients were reoperated 3 times, and three had two surgeries, resulting in a total of 64 procedures. The number of days between SSI diagnosis and surgical intervention did not influence mortality in both univariate and multivariable analyses (Hazard ratio [HR] 1.03, 95% CI 0.93-1.13). Early debridement (<24 h) did not influence rates of antibiotic prescription at discharge (P = 0.53) or hospital length of stay (LOS) (P = 0.16). Higher neutrophil-lymphocyte ratios (NLRs) were associated with the lower survival (HR 1.05, 95% Confidence interval [CI] 1.01-1.08). Multiple cutoffs were tested and values above 3.5 are more significantly associated with worse outcomes (HR 2.2; 95%CI 1.1-4.2). Conclusion: Early debridement does not seem to influence the survival, rates of antibiotic at discharge, or hospital LOS of patients presenting with SSI after neurosurgery for intracranial tumors. High NLRs are strong predictors of worse prognosis in this population.

Disrespect and abuse during childbirth in maternity hospitals in Piauí, Brazil: A cross-sectional study.

OBJECTIVES: To assess the prevalence and associated factors of disrespect and abuse during childbirth in Piauí, Brazil. METHODS: A cross-sectional study was performed with 698 postpartum women in 21 maternity hospitals in 14 municipalities between August 2018 and September 2019. Face-to-face interviews were performed at least 6 h after birth, with an assessment of disrespect and abuse during childbirth. Robust Poisson regression was used, with calculation of the adjusted prevalence ratio (aPR) and 95% confidence intervals (95% CIs). RESULTS: There was evidence that 19.8% of women experienced at least one type of disrespect and abuse during childbirth, with verbal abuse (12.6%), noncompliance with professional standards (11.6%), and health service restrictions being more common (8.3%). There was an association of disrespect and abuse during childbirth with women aged 10 to 19 years (aPR, 1.97; 95% CI, 1.58-2.44), absence of companions (aPR, 2.43; 95% CI, 1.85-2.89), cesarean sections after labor (aPR, 2.19; 95% CI, 1.64-3.59), public hospitals (aPR, 1.87; 95% CI, 1.42-2.85), and in the countryside (aPR, 2.29; 95% CI, 1.81-3.98). CONCLUSION: There was a high prevalence of disrespect and abuse during childbirth in Piauí, Brazil, associated with structural conditions of the services, care practices, and characteristics of women.

Analysis of the structural adequacy of maternity hospitals in Piauí, Brazil, 2018-2019 / Análise da adequação estrutural das maternidades do Piauí, Brasil, 2018-2019

Abstract Objectives: to evaluate the structure and adequacy of maternal healthcare facilities in Piauí. Methods: cross-sectional study in 26 hospitals with more than 200 births/year between 2018-2019. The structure was assessed by direct observation and interview with manager, in four domains: physical aspects, human resources, equipment, and drugs. Fisher's chi-square/exact tests were used to assess differences in adequacy of structure. Results: only 46.2% of the maternal healthcare facilities had pre-delivery, parturition and immediate post-partum room. Pediatricians (73.1%) and anesthesiologists (61.5%) were the least present professionals on-duty regime. Regarding drugs, magnesium sulfate and oxytocin were observed in 76.9% of hospitals. Overall adequacy was 23.1%, being higher in maternal healthcare facilities in the capital (p=0.034) and in private ones (p=0.031). Conclusions: Data show inequalities in the structure of maternity hospitals of the state. The absence of health professionals, essential drugs, and appropriate physical structure can expose women and newborns to unnecessary and avoidable risks.

Resumo Objetivos: avaliar a estrutura e adequação das maternidades do Piauí. Métodos: estudo transversal em 26 hospitais com mais de 200 partos/ano entre 2018 e 2019. A estrutura foi avaliada por observação direta e entrevista com gestor, em quatro domínios: aspectos físicos, recursos humanos, equipamentos e medicamentos. Foram empregados os testes do quiquadrado/exato de Fisher para avaliar diferenças na adequação da estrutura. Resultados: apenas 46,2% das maternidades tinham quarto pré-parto, parto e puerpério. Pediatras (73,1%) e anestesistas (61,5%) foram os profissionais menos presentes em regime de plantão. Dos medicamentes, sulfato de magnésio e ocitocina foram observados em 76,9% dos hospitais. A adequação global foi de 23,1%, sendo maior em maternidades da capital (p=0,034) e privadas (p=0,031) Conclusões: os dados exibem desigualdades na estrutura das maternidades do estado. A ausência de profissionais de saúde, medicamentos essenciais e estrutura física apropriada pode expor mulheres e recém-nascidos a riscos desnecessários e evitáveis.

Frequency of lipid-poor adrenal adenomas in magnetic resonance imaging examinations of the abdomen / Frequência de adenomas adrenais pobres em lipídios em exames de ressonância magnética abdominal

Abstract Objective: To estimate the frequency of lipid-poor adenomas (LPAs) in magnetic resonance imaging (MRI) examinations. Materials and Methods: We retrospectively investigated adrenal lesions on MRI examinations performed in a total of 2,014 patients between January 2016 and December 2017. After exclusions, the sample comprised 69 patients with 74 proven adenomas. Two readers (reader 1 and reader 2) evaluated lesion size, laterality, homogeneity, signal drop on out-of-phase (OP) images, and the signal intensity index (SII). An LPA was defined as a lesion with no signal drop on OP images and an SII < 16.5%. For 68 lesions, computed tomography (CT) scans (obtained within one year of the MRI) were also reviewed. Results: Of the 69 patients evaluated, 42 (60.8%) were women and 27 (39.2%) were men. The mean age was 59.2 ± 14.1 years. Among the 74 confirmed adrenal adenomas evaluated, the mean lesion size was 18.5 ± 7.7 mm (range, 7.0-56.0 mm) for reader 1 and 21.0 ± 8.3 mm (range, 7.0-55.0 mm) for reader 2 (p = 0.055). On the basis of the signal drop in OP MRI sequences, both readers identified five (6.8%) of the 74 lesions as being LPAs. When determined on the basis of the SII, that frequency was three (4.0%) for reader 1 and four (5.4%) for reader 2. On CT, 21 (30.8%) of the 68 lesions evaluated were classified as LPAs. Conclusion: The prevalence of LPA was significantly lower on MRI than on CT. That prevalence tends to be even lower when the definition of LPA relies on a quantitative analysis rather than on a qualitative (visual) analysis.

Resumo Objetivo: Estimar a frequência de adenomas pobres em lipídios (APLs) em exames de ressonância magnética (RM). Materiais e Métodos: Investigaram-se, retrospectivamente, as lesões adrenais em exames de RM realizados de janeiro de 2016 a dezembro de 2017. Um total de 2.014 pacientes foi submetido a exames abdominais e, após exclusões, 69 pacientes com 74 adenomas foram recuperados. Determinaram-se o tamanho da lesão, a lateralidade, a homogeneidade, a queda do sinal em imagens fora-de-fase (FF) e o índice de intensidade do sinal (IIS). Foram utilizadas as seguintes definições para APLs: sem queda de sinal nas imagens FF e IIS < 16,5%. Para 68 lesões, havia imagens de tomografia computadorizada (TC), com intervalo de até um ano da RM, que também foram analisadas. Resultados: Sessenta e nove pacientes foram incluídos, sendo 42 mulheres (60,8%) e 27 homens (39,2%). A média de idade foi 59,2 ± 14,1 anos. O tamanho médio do adenoma adrenal foi 18,5 ± 7,7 mm para o leitor 1 (7,0-56,0 mm) e 21,0 ± 8,3 mm (7,0-55,0 mm) para o leitor 2 (p = 0,055). A queda de sinal nas imagens FF mostrou que a frequência de APLs para ambos os leitores foi 6,8% (5/74). Para a análise quantitativa, a frequência foi 4,0% (3/74) para o leitor 1 e 5,4% (4/74) para o leitor 2. A frequência de APLs nas imagens de TC foi 21/68 lesões (30,8%). Conclusão: A prevalência de APLs em imagens de RM foi significativamente menor do que em exames de TC. Essa prevalência tende a ser ainda menor quando a definição de APL é baseada na análise quantitativa (IIS < 16,5%), em vez da análise visual.

Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases.

OBJECTIVE: To determine the immunogenicity of the third dose of CoronaVac vaccine in a large population of patients with autoimmune rheumatic diseases (ARD) and the factors associated with impaired response. METHODS: Adult patients with ARD and age-balanced/sex-balanced controls (control group, CG) previously vaccinated with two doses of CoronaVac received the third dose at D210 (6 months after the second dose). The presence of anti-SARS-CoV-2 S1/S2 IgG and neutralising antibodies (NAb) was evaluated previously to vaccination (D210) and 30 days later (D240). Patients with controlled disease suspended mycophenolate mofetil (MMF) for 7 days or methotrexate (MTX) for 2 weekly doses after vaccination. RESULTS: ARD (n=597) and CG (n=199) had comparable age (p=0.943). Anti-S1/S2 IgG seropositivity rates significantly increased from D210 (60%) to D240 (93%) (p<0.0001) in patients with ARD. NAb positivity also increased: 38% (D210) vs 81.4% (D240) (p<0.0001). The same pattern was observed for CG, with significantly higher frequencies for both parameters at D240 (p<0.05). Multivariate logistic regression analyses in the ARD group revealed that older age (OR=0.98, 95% CI 0.96 to 1.0, p=0.024), vasculitis diagnosis (OR=0.24, 95% CI 0.11 to 0.53, p<0.001), prednisone ≥5 mg/day (OR=0.46, 95% CI 0.27 to 0.77, p=0.003), MMF (OR=0.30, 95% CI 0.15 to 0.61, p<0.001) and biologics (OR=0.27, 95% CI 0.16 to 0.46, p<0.001) were associated with reduced anti-S1/S2 IgG positivity. Similar analyses demonstrated that prednisone ≥5 mg/day (OR=0.63, 95% CI 0.44 to 0.90, p=0.011), abatacept (OR=0.39, 95% CI 0.20 to 0.74, p=0.004), belimumab (OR=0.29, 95% CI 0.13 to 0.67, p=0.004) and rituximab (OR=0.11, 95% CI 0.04 to 0.30, p<0.001) were negatively associated with NAb positivity. Further evaluation of COVID-19 seronegative ARD at D210 demonstrated prominent increases in positivity rates at D240 for anti-S1/S2 IgG (80.5%) and NAb (59.1%) (p<0.0001). CONCLUSIONS: We provide novel data on a robust response to the third dose of CoronaVac in patients with ARD, even in those with prevaccination COVID-19 seronegative status. Drugs implicated in reducing immunogenicity after the regular two-dose regimen were associated with non-responsiveness after the third dose, except for MTX. Trial registration number NCT04754698.

Inactivated SARS-CoV-2 vaccine in primary Sjögren's syndrome: humoral response, safety, and effects on disease activity.

INTRODUCTION: There is no study specifically focused on SARS-CoV-2 vaccine in primary Sjögren's syndrome (pSS). OBJECTIVES: To assess the immunogenicity, safety, possible effects on disease activity, and autoantibody profile of the Sinovac-CoronaVac vaccine in pSS. METHODS: Fifty-one pSS patients and 102 sex- and age-balanced controls without autoimmune diseases were included in a prospective phase 4 trial of the Sinovac-CoronaVac vaccine (two doses 28 days apart, D0/D28). Participants were assessed in three face-to-face visits (D0/D28 and six weeks after the 2nd dose (D69)) regarding adverse effects; clinical EULAR Sjögren's Syndrome Disease Activity Index (clinESSDAI); anti-SARS-CoV-2 S1/S2 IgG (seroconversion (SC) and geometric mean titers (GMT)); neutralizing antibodies (NAb); and pSS autoantibody profile. RESULTS: Patients and controls had comparable female sex frequency (98.0% vs. 98.0%, p = 1.000) and mean age (53.5 ± 11.7 vs. 53.4 ± 11.4 years, p = 0.924), respectively. On D69, pSS patients presented moderate SC (67.5% vs. 93.0%, p < 0.001) and GMT (22.5 (95% CI 14.6-34.5) vs. 59.6 (95% CI 51.1-69.4) AU/mL, p < 0.001) of anti-SARS-CoV-2 S1/S2 IgG but lower than controls, and also, moderate NAb frequency (52.5% vs. 73.3%, p = 0.021) but lower than controls. Median neutralizing activity on D69 was comparable in pSS (58.6% (IQR 43.7-63.6)) and controls (64% (IQR 46.4-81.1)) (p = 0.219). Adverse events were mild. clinESSDAI and anti-Ro(SS-A)/anti-La(SS-B) levels were stable throughout the study (p > 0.05). CONCLUSION: Sinovac-CoronaVac vaccine is safe in pSS, without a deleterious impact on disease activity, and has a moderate short-term humoral response, though lower than controls. Thus, a booster dose needs to be studied in these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04754698. Key Points • Sinovac-CoronaVac vaccine is safe in pSS, without a detrimental effect on systemic disease activity, and has a moderate short-term humoral response • A booster dose should be considered in these patients.