Efficacy of ultrasound-guided infiltration with levobupivacaine and triamcinolone for myofascial pain syndrome of the quadratus lumborum: a retrospective observational study

Abstract Introduction and objectives: Myofascial Pain Syndrome (MPS) of the Quadratus Lumborum muscle (QL) is a frequent cause of chronic low back pain. With this study, we aimed to assess the efficacy of ultrasound-guided infiltration with 0.25% levobupivacaine and 40 mg triamcinolone for MPS of the QL. Methods: Observational and retrospective study of participants submitted to ultrasound-guided infiltration of the QL muscle from January 1, 2015 to June 31, 2019. Pain intensity was assessed using the five-point pain Numeric Rating Scale (NRS): pre-intervention, at 72 hours, 1 month, 3 months and 6 months post-intervention. Additional data collected were demographic characteristics, opioid consumption, and adverse effects. Results: We assessed 90 participants with mean age of 55.2 years. Sixty-eight percent of participants were female. Compared to the pre-intervention assessment, there was an improvement in pain at 72 hours (Mean Difference [MD = 3.085]; 95% CI: 2.200-3.970, p < 0.05), at the 1st month (MD = 2.644; 95% CI: 1.667-3.621, p < 0.05), at the 3rdmonth (MD = 2.017; 95% CI: 0.202-2.729, p < 0.05) and at the 6th month (MD = 1.339; 95% CI 0.378-2.300, p < 0.05), post-intervention. No statistically significant differences in opioid consumption were observed. No adverse effects associated with the technique were reported. Conclusions: Ultrasound-guided infiltration of the QL muscle is a safe and effective procedure for the treatment of pain in the QL MPS within 6 months post-intervention.

GO-DACT: a phase 3b randomised, double-blind, placebo-controlled trial of GOlimumab plus methotrexate (MTX) versus placebo plus MTX in improving DACTylitis in MTX-naive patients with psoriatic arthritis.

OBJECTIVES: To assess the efficacy of golimumab in combination with methotrexate (MTX) versus MTX monotherapy in psoriatic arthritis (PsA) dactylitis. METHODS: Multicentre, investigator-initiated, randomised, double-blind, placebo-controlled, parallel-design phase 3b trial in 11 Portuguese rheumatology centres. Patients with PsA along with active dactylitis and naive to MTX and biologic disease-modifying antirheumatic drugs (bDMARDs) were randomly assigned to golimumab or placebo, both in combination with MTX. The primary endpoint was Dactylitis Severity Score (DSS) change from baseline to week 24. Key secondary endpoints included DSS and Leeds Dactylitis Index (LDI) response, and changes from baseline in the LDI and MRI dactylitis score. Analysis was by intention-to-treat for the primary endpoint. RESULTS: Twenty-one patients received golimumab plus MTX and 23 MTX monotherapy for 24 weeks. One patient from each arm discontinued. Patient inclusion was halted at 50% planned recruitment due to a favourable interim analysis. Median baseline DSS was 6 in both arms. By week 24, patients treated with golimumab plus MTX exhibited significantly greater improvements in DSS relative to MTX monotherapy (median change of 5 vs 2 points, respectively; p=0.026). In the golimumab plus MTX arm, significantly higher proportions of patients achieved at least 50% or 70% improvement in DSS and 20%, 50% or 70% improvement in LDI in comparison to MTX monotherapy. CONCLUSIONS: The combination of golimumab and MTX as first-line bDMARD therapy is superior to MTX monotherapy for the treatment of PsA dactylitis. TRIAL REGISTRATION NUMBER: NCT02065713.

Seroprevalence of IgG and IgM anti-SARS-CoV-2 among voluntary blood donors in Rio de Janeiro, Brazil

Background: In Brazil, mathematical models for derivingestimates and projections of COVID-19 cases have been developed without data on asymptomatic SARS-CoV-2 infection. We estimated the seroprevalence of antibodies to SARS-CoV-2 among blood donors in the State of Rio de Janeiro. Methods: Data were collected on 2,857 blood donors from April 14 to 27, 2020. We report the crude prevalence of antibodies to SARS-CoV-2, the weighted prevalence by the total state population, and adjusted prevalence estimates for test sensitivity and specificity. To establish the correlates of SARS-CoV-2 prevalence, we used logistic regression models. The analysis included period and site of blood collection, sociodemographic characteristics, and place of residence. Results: The proportion of SARS-Cov-2 positive tests without any adjustment was 4.0% (95% CI 3.3-4.7%), and the weighted prevalence was 3.8% (95% CI 3.1-4.5%). Further adjustment by test sensitivity and specificity produced lower estimates, 3.6% (95% CI 2.7-4.4%) and 3.3% (95% CI 2.6-4.1%), respectively. The variable most significantly associated with the crude prevalence was the period of blood collection: the later the period, the higher the prevalence. Regarding socio-demographic characteristics, the younger the blood donors, the higher the prevalence, and the lower the educational level, the higher the odds of a positive SARS-Cov-2 antibody. Similar results were found for the weighted prevalence. Discussion: Although our findings resulted from a convenience sample, they match some basic premises: the increasing trend over time, since the epidemic curve in the state is still on the rise; the higher prevalence among the youngest who are more likely to circulate; and the higher prevalence among the less educated as they have more difficulties in following the social distancing recommendations. Despite the study limitations, it is possible to infer that protective levels of natural herd immunity to SARS-CoV-2 are far from being reached in Rio de Janeiro. (AU)

Impact of postoperative cognitive decline in quality of life: a prospective study / Impacto do declínio cognitivo pós-operatório na qualidade de vida: estudo prospectivo

Abstract Background Regardless the progress in perioperative care postoperative cognitive decline (PCD) has been accepted unequivocally as a significant and frequent complication of surgery in older patients. The aim of this study was to evaluate the incidence of postoperative cognitive decline and its influence on quality of life three months after surgery. Methods Observational, prospective study in a Post-Anesthesia Care Unit (PACU) in patients aged above 45 years, after elective major surgery. Cognitive function was assessed with Montreal Cognitive Assessment (MOCA); Quality of life (QoL) was assessed using SF-36 Health Survey (SF-36). Assessments were performed preoperatively (T0) and 3 months after surgery (T3). Results Forty-one patients were studied. The incidence of PCD 3 months after surgery was 24%. At T3 MOCA scores were lower in patients with PCD (median 20 vs. 25, p = 0.009). When comparing the median scores for each of SF-36 domains, there were no differences between patients with and without PCD. In patients with PCD, and comparing each of SF-36 domains obtained before and three months after surgery, had similar scores for every of the 8 SF-36 areas while patients without PCD had better scores for six domains. At T3 patients with PCD presented with higher levels of dependency in personal activities of daily living (ADL). Conclusion Three months after surgery patients without PCD had significant improvement in MOCA scores. Patients with PCD obtained no increase in SF-36 scores but patients without PCD improved in almost all SF-36 domains. Patients with PCD presented higher rates of dependency in personal ADL after surgery.

Resumo Justificativa e objetivo Independente do progresso do tratamento no período perioperatório, o declínio cognitivo no pós-operatório (DCPO) é inequivocamente aceito como uma complicação importante e frequente da cirurgia em pacientes mais velhos. O objetivo deste estudo foi avaliar a incidência de DCPO e sua influência na qualidade de vida três meses após a cirurgia. Métodos Estudo prospectivo observacional conduzido em Sala de Recuperação Pós-anestesia (SRPA) com pacientes de idade superior a 45 anos, após cirurgia eletiva de grande porte. A função cognitiva foi avaliada com o teste de Avaliação Cognitiva de Montreal (MOCA) e a qualidade de vida (QV) com o Questionário sobre Qualidade de Vida (SF-36). As avaliações foram realizadas no pré-operatório (T0) e três meses após a cirurgia (T3). Resultados Foram avaliados 41 pacientes. A incidência de DCPO três meses após a cirurgia foi de 24%. Em T3, os escores MOCA foram menores nos pacientes com DCPO (mediana 20 vs. 25, p = 0,009). Ao comparar as medianas dos escores para cada um dos domínios do SF-36, não observamos diferenças entre os pacientes com e sem DCPO. Ao comparar cada um dos domínios do SF-36 obtidos antes e após três meses de cirurgia, os pacientes com DCPO apresentaram resultados semelhantes para cada uma das oito áreas do SF-36, enquanto pacientes sem DCPO apresentaram resultados melhores em seis domínios. Em T3, os pacientes com DCPO apresentaram níveis mais elevados de dependência na realização de atividades cotidianas. Conclusão Três meses após a cirurgia, os pacientes sem DCPO apresentaram melhora significativa dos escores MOCA. Os pacientes com DCPO não apresentaram aumento dos escores SF-36, mas os pacientes sem DCPO apresentaram melhora em quase todos os domínios do SF-36. Os pacientes com DCPO apresentaram taxas mais elevadas de dependência na realização de atividades cotidianas após a cirurgia.

Anticentromere antibody positive Ackerman's Syndrome with Granulomatous Anterior Uveitis.

Ackerman's Syndrome or Intersticial Granulomatous Dermatitis with Arthritis has been an issue of increasing number of reports in the last decade which had focused its heterogeneous cutaneous and rheumatologic expression besides the initial manifestations reported by Ackerman and his group. Granulomatosis anterior uveitis has not been previously described. Some patients are reported to have positive autoantibodies but association with anticentromere antibodies has not been previously described as well, to our knowledge. We report a new case of Ackerman Syndrome with cutaneous, articular and ocular involvement with positive anticentromere antibodies successfully treated with systemic steroids, methotrexate, hydroxychloroquine and cyclosporine. The ocular involvement and the association of anticentromere antibodies lead us to hypothesize that constellation of symptoms and autoimmune mechanisms of this uncommon multisystemic syndrome are yet to be clarified.

[Impact of postoperative cognitive decline in quality of life: a prospective study]. / Impacto do declínio cognitivo pós­operatório na qualidade de vida: estudo prospectivo.

BACKGROUND: Regardless the progress in perioperative care postoperative cognitive decline (PCD) has been accepted unequivocally as a significant and frequent complication of surgery in older patients. The aim of this study was to evaluate the incidence of postoperative cognitive decline and its influence on quality of life three months after surgery. METHODS: Observational, prospective study in a Post-Anesthesia Care Unit (PACU) in patients aged above 45 years, after elective major surgery. Cognitive function was assessed with Montreal Cognitive Assessment (MOCA); Quality of life (QoL) was assessed using SF-36 Health Survey (SF-36). Assessments were performed preoperatively (T0) and 3 months after surgery (T3). RESULTS: Forty-one patients were studied. The incidence of PCD 3 months after surgery was 24%. At T3 MOCA scores were lower in patients with PCD (median 20 vs. 25, p=0.009). When comparing the median scores for each of SF-36 domains, there were no differences between patients with and without PCD. In patients with PCD, and comparing each of SF-36 domains obtained before and three months after surgery, had similar scores for every of the 8 SF-36 areas while patients without PCD had better scores for six domains. At T3 patients with PCD presented with higher levels of dependency in personal activities of daily living (ADL). CONCLUSION: Three months after surgery patients without PCD had significant improvement in MOCA scores. Patients with PCD obtained no increase in SF-36 scores but patients without PCD improved in almost all SF-36 domains. Patients with PCD presented higher rates of dependency in personal ADL after surgery.

Effectiveness of early adalimumab therapy in psoriatic arthritis patients from Reuma.pt - EARLY PsA.

Objective To compare outcomes in psoriatic arthritis (PsA) patients initiating adalimumab (ADA), with short- and long-term disease duration and to evaluate the potential effect of concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARD) or glucocorticoids. Methods Analyses included adult PsA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) between June 2008-June 2016 who received ADA for ≥3 months. Psoriatic Arthritis Response Criteria (PsARC) response, tender and swollen joint count, inflammatory parameters, patient (PtGA) and physician global assessment (PhGA), Disease Activity Score-28 joints (DAS28), and Health Assessment Questionnaire Disability Index (HAQ-DI) were compared between patients with <5 years of disease (early PsA) and those with ≥5 years of disease duration (late PsA). Time to achieving PsARC response was estimated using the Kaplan-Meier method. Results Of 135 PsA patients treated with ADA, 126 had information on disease duration (earlyPsA, n=41). PsARC response was achieved by 72.9% of the patients (88.0% early PsA vs 62.2% late PsA; P=0.022) after 3 months and by 85.4% after 24 months (100% early PsA vs 75.9% late PsA; P=0.044). Early PsA patients achieved significantly less painful joints (2.7 vs 6.7, p=0.006), lower mean C-reactive protein (0.5 mg/dL vs 1.3 mg/dL; P=0.011), and PhGA (18.3 vs 28.1; P=0.020) at 3 months. In the long term, early PsA patients also had fewer swollen joints (0.3 vs 1.7; P=0.030) and lower PhGA (6.3 vs 21.9; P<0.001), C-reactive protein (0.4 mg/dL vs 1.0 mg/dL; P=0.026), and DAS28 (2.2 vs 3.2; P=0.030). HAQ-DI decreased in both groups reaching a mean value at 24 months of 0.4 and 0.8 (P=ns) in early and late PsA, respectively. Early PsA patients obtained PsARC response more rapidly than late PsA (3.8 and 7.4 months, respectively; P=0.008). Concomitant csDMARDs showed clinical benefit (2-year PsARC response, 88.3% vs 60.0%; P=0.044). Concomitant glucocorticoids had no effect on PsARC response over 2 years of follow-up. Persistence on ADA was similar in both groups. Conclusion Early PsA patients had a greater chance of improvement after ADA therapy and better functional outcome, and achieved PsARC response more rapidly than late PsA. In this cohort, comedication with csDMARDs was beneficial over 2 years.

Erk5 nuclear location is independent on dual phosphorylation, and favours resistance to TRAIL-induced apoptosis.

Nucleocytoplasmic shuttling of multiple signalling proteins is critical in the control of processes such as cell proliferation, differentiation, or apoptosis. One group of proteins whose activity depends on this nucleocytoplasmic traffic includes the mitogen-activated protein kinases. Usually, these kinases reside in the cytoplasm and move to the nucleus upon dual phosphorylation. One of these kinases, Erk5, has been found to reside in the nucleus of breast cancer cells that overexpress the ErbB2 receptor. This raises questions with respect to the mechanisms implicated in Erk5 nuclear location in these cells, as well as the biological consequences of this nuclear residency. In breast cancer cells overexpressing ErbB2, Erk5 dual phosphorylation required ErbB2 tyrosine kinase activity; however, Erk5 nuclear residency did not require ErbB2 activity. Furthermore, translocation of Erk5 from the cytosol to the nucleus occurred in the absence of dual phosphorylation. Nuclear residency of Erk5 in these cells depended on the integrity of a nuclear localization signal present in the unique C-terminus of Erk5. The Erk5 form expressed by these breast cancer cells included the N- and C-terminal cytoplasmic targeting signals, yet Erk5 was nuclear, and remained at this location throughout the interphase without being tightly bound to DNA. Biological studies using a mutant Erk5 that accumulates in the nucleus indicate that nuclear Erk5 favours MEF2-dependent transcriptional activity, and inhibits TRAIL-induced cell death.

The extracellular linker of pro-neuregulin-alpha2c is required for efficient sorting and juxtacrine function.

The neuregulins (NRGs) play important roles in animal physiology, and their disregulation has been linked to diseases such as cancer or schizophrenia. The NRGs may be produced as transmembrane proteins (proNRGs), even though they lack an N-terminal signal sequence. This raises the question of how NRGs are sorted to the plasma membrane. It is also unclear whether in their transmembrane state, the NRGs are biologically active. During studies aimed at solving these questions, we found that deletion of the extracellular juxtamembrane region termed the linker, decreased cell surface exposure of the mutant proNRG(DeltaLinker), and caused its entrapment at the cis-Golgi. We also found that cell surface-exposed transmembrane NRG forms retain biological activity. Thus, a mutant whose cleavage is impaired but is correctly sorted to the plasma membrane activated ErbB receptors in trans and also stimulated proliferation. Because the linker is implicated in surface sorting and the regulation of the cleavage of transmembrane NRGs, our data indicate that this region exerts multiple important roles in the physiology of NRGs.

ERK5 activates NF-kappaB in leukemic T cells and is essential for their growth in vivo.

MAPK cascades play a central role in the cellular response to the environment. The pathway involving the MAPK ERK5 mediates growth factor- and stress-induced intracellular signaling that controls proliferation or survival depending upon the cell context. In this study, we show that reducing ERK5 levels with a specific small hairpin RNA 5 (shERK5) reduced cell viability, sensitized cells to death receptor-induced apoptosis, and blocked the palliative effects of phorbol ester in anti-Fas Ab-treated cells. shERK5 decreased nuclear accumulation of the NF-kappaB p65 subunit, and conversely, ectopic activation of ERK5 led to constitutive nuclear localization of p65 and increased its ability to trans activate specific reporter genes. Finally, the T lymphoma cell line EL-4, upon expression of shERK5, proliferated in vitro, but failed to induce s.c. tumors in mice. Our results suggest that ERK5 is essential for survival of leukemic T cells in vivo, and thus represents a promising target for therapeutic intervention in this type of malignancy.