Attitudes and barriers to pulmonary arterial hypertension screening in systemic sclerosis patients: A survey of UK-based rheumatologists.

Objectives: The objectives were to explore rheumatologists' current clinical screening practices of pulmonary arterial hypertension in patients with systemic sclerosis in the United Kingdom and to identify barriers to screening and consider potential solutions. Methods: A survey of 31 questions was developed and included six sections: clinician demographics, the importance of screening, screening practices, barriers to screening, treatment and patient education. The survey was disseminated among rheumatologists working in the United Kingdom. Results: Forty-four rheumatologists working in the United Kingdom participated in the study, and the majority completed all the questions. Around one-third (37.0%) worked in specialised systemic sclerosis units (university or general hospitals (54.5% and 45.4%, respectively)). The majority recognised that systemic sclerosis-pulmonary arterial hypertension is a major cause of morbidity and mortality. Over half (60.0%) reported using the DETECT algorithm to screen for systemic sclerosis-pulmonary arterial hypertension, although other algorithms were also sometimes used. All of the respondents utilised transthoracic echocardiogram, and almost all (95.0%) performed pulmonary function tests for screening purposes. Various challenges and barriers were identified relating to systemic sclerosis-pulmonary arterial hypertension screening, with the difficulty in interpreting results from other hospitals and extended wait times for diagnostic tests being the most reported (76.0% and 74.0%, respectively). Most respondents agreed that access to key investigations (87.0%), ongoing clinician education (82.0%), multidisciplinary meetings (79.5%) and a better understanding of proposed screening algorithms (79.5%) could be potential solutions. Conclusion: Screening patients with systemic sclerosis for pulmonary arterial hypertension is crucial to improve survival, but variable practices exist among UK rheumatologists. Solutions include educating healthcare professionals on guidelines, sharing information between centres and integrating care services.

Miettinen and Nurminen score statistics revisited.

It is commonly necessary to perform inferences on the difference, ratio, and odds ratio of two proportions p1 and p2 based on two independent samples. For this purpose, the most common asymptotic statistics are based on the score statistics (S-type statistics). As these do not correct the bias of the estimator of the product pi (1-pi), Miettinen and Nurminen proposed the MN-type statistics, which consist of multiplying the statistics S by (N-1)/N, where N is the sum of the two sample sizes. This paper demonstrates that the factor (N-1)/N is only correct in the case of the test of equality of two proportions, providing the estimation of the correct factor (AU-type statistics) and the minimum value of the same (AUM-type statistics). Moreover, this paper assesses the performance of the four-type statistics mentioned (S, MN, AU and AUM) in one and two-tailed tests, and for each of the three parameters cited (d, R and OR). We found that the AUM-type statistics are the best, followed by the MN type (whose performance was most similar to that of AU-type). Finally, this paper also provides the correct factors when the data are from a multinomial distribution, with the novelty that the MN and AU statistics are similar in the case of the test for the odds ratio.

Specific Cellular and Humoral Response after the Third Dose of Anti-SARS-CoV-2 RNA Vaccine in Patients with Immune-Mediated Rheumatic Diseases on Immunosuppressive Therapy.

OBJECTIVE: Data on cellular and humoral immunogenicity after the third dose of anti-SARS-CoV-2 vaccines in patients with immune-mediated rheumatic diseases (IMRDs) are scarce. Herein, we evaluated the adaptive immune response in IMRD patients treated with different immunosuppressive therapies (conventional synthetic disease-modifying antirheumatic drugs [csDMARDs], biological disease-modifying antirheumatic drugs [bDMARDs], and targeted synthetic disease-modifying antirheumatic drugs [tsDMARDs]) after the booster of the anti-SARS-CoV-2 vaccine to determine whether any drug reduced the vaccine's response. METHODS: A single-center prospective study was conducted, including patients presenting with IMRD and healthy controls (HC). Specific anti-SARS-CoV-2 interferon-gamma (IFN-γ) production was evaluated between 8-12 weeks after the third dose of the SARS-CoV-2 vaccine. In addition, anti-Spike IgG antibody titers were also measured. RESULTS: Samples were obtained from 79 IMRD patients (51 women, 28 men; mean age 57 ± 11.3 years old): 43 rheumatoid arthritis, 10 psoriatic arthritis, 14 ankylosing spondylitis, 10 undifferentiated spondyloarthritis, and 2 inflammatory bowel disease-associated spondyloarthritis (IBD-SpA). In total, 31 HC (mean age 50.9 ± 13.1 years old, 67.7% women) were included in the study. Post-vaccine results displayed positive T-cell immune responses in 68 out of 79 (86.1%) IMRD patients (82.3% of those without prior COVID-19). All HC and IMRDs patients had an antibody response against the SARS-CoV-2 receptor-binding domain; however, the HC response was significantly higher (median of 18,048 AU/mL) than in IMRDs patients (median of 6590.3 AU/mL, p < 0.001). MTX and leflunomide were associated with lower titers of IgG and IFN-γ responses. Among bDMARDs, adalimumab, etanercept, and guselkumab are associated with reduced cellular responses. CONCLUSION: Our preliminary data show that the majority of our IMRD patients develop cellular and humoral responses after the SARS-CoV-2 booster vaccination, emphasizing the relevance of vaccination in this group. However, the magnitude of specific responses was dependent on the immunosuppressive therapy administered. Specific vaccination protocols and personalized decisions about boosters are essential for these patients.

Long-Term Benefit of Perlingual Polybacterial Vaccines in Patients with Systemic Autoimmune Diseases and Active Immunosuppression.

INTRODUCTION: We have previously shown that trained-immunity-based vaccines, namely TIbV, significantly reduce the rate of recurrent infections, both of the respiratory tract (RRTI) and urinary tract infections (RUTI) in SAD patients on disease-modifying drugs (DMARDs). OBJECTIVE: We evaluated the frequency of RRTI and RUTI from 2018 to 2021 in those SAD patients that received TIbV until 2018. Secondarily, we evaluated the incidence and clinical course of COVID-19 in this cohort. METHODS: A retrospective observational study was conducted in a cohort of SAD patients under active immunosuppression immunized with TIbV (MV130 for RRTI and MV140 for RUTI, respectively). RESULTS: Forty-one SAD patients on active immunosuppression that were given TIbV up to 2018 were studied for RRTI and RUTI during the 2018-2021 period. Approximately half of the patients had no infections during 2018-2021 (51.2% no RUTI and 43.5% no RRTI at all). When we compared the 3-year period with the 1-year pre-TIbV, RRTI (1.61 ± 2.26 vs. 2.76 ± 2.57; p = 0.002) and RUTI (1.56 ± 2.12 vs. 2.69 ± 3.07; p = 0.010) episodes were still significantly lower. Six SAD patients (four RA; one SLE; one MCTD) with RNA-based vaccines were infected with SARS-CoV-2, with mild disease. CONCLUSIONS: Even though the beneficial protective effects against infections of TIbV progressively decreased, they remained low for up to 3 years, with significantly reduced infections compared to the year prior to vaccination, further supporting a long-term benefit of TIbV in this setting. Moreover, an absence of infections was observed in almost half of patients.

Beamforming Techniques for Passive Radar: An Overview.

Passive radar is an interesting approach in the context of non-cooperative target detection. Because the signal source takes advantage of the so-called illuminator of opportunity (IoO), the deployed system is silent, allowing the operator cheap, portable, and practically undetectable deployments. These systems match perfectly with the use of antenna arrays to take advantage of the additional gains provided by the coherent combination of the signals received at each element. To obtain these benefits, linear processing methods are required to enhance the system's performance. In this work, we summarize the main beamforming methods in the literature to provide a clear picture of the current state of the art. Next, we perform an analysis of the benefits and drawbacks and explore the chance of increasing the number of antenna elements. Finally, we identify the major challenges to be addressed by researchers in the future.

Hubert's multi-rater kappa revisited.

There is a frequent need to measure the degree of agreement among R observers who independently classify n subjects within K nominal or ordinal categories. The most popular methods are usually kappa-type measurements. When R = 2, Cohen's kappa coefficient (weighted or not) is well known. When defined in the ordinal case while assuming quadratic weights, Cohen's kappa has the advantage of coinciding with the intraclass and concordance correlation coefficients. When R > 2, there are more discrepancies because the definition of the kappa coefficient depends on how the phrase 'an agreement has occurred' is interpreted. In this paper, Hubert's interpretation, that 'an agreement occurs if and only if all raters agree on the categorization of an object', is used, which leads to Hubert's (nominal) and Schuster and Smith's (ordinal) kappa coefficients. Formulae for the large-sample variances for the estimators of all these coefficients are given, allowing the latter to illustrate the different ways of carrying out inference and, with the use of simulation, to select the optimal procedure. In addition, it is shown that Schuster and Smith's kappa coefficient coincides with the intraclass and concordance correlation coefficients if the first coefficient is also defined assuming quadratic weights.

Megaesófago por persistencia del cuarto arco aórtico derecho en un perro pastor alemán / Megaesophagus due to persistence of the fourth right aortic arch in a german shepherd dog

Se diagnosticó un megaesófago secundario por anomalías de anillo vascular a una hembra, de raza Pastor Alemán, de nueve semanas de edad, con historia de regurgitación intermitente posterior al destete, problemas respiratorios, pérdida de peso y retraso en el crecimiento. Un estudio radiográfico simple de tórax y un esofagograma usando como material de contraste el bario, confirmaron la presencia de una gran dilatación esofágica craneal a la base del corazón, conformada por tres saculaciones. Un mes después, la paciente fue sometida a una toracotomía intercostal izquierda para seccionar el ligamento arterioso y liberar la constricción esofágica, lo que permitió establecer el diagnóstico definitivo de megaesófago secundario adquirido, por persistencia del cuarto arco aórtico derecho. Luego de la cirugía, se inició un método de alimentación en un plano elevado, con una dieta blanda, la cual se mantuvo con leves variaciones de manera permanente. La paciente mostró remisión completa de los signos clínicos a pesar de la persistencia del megaesófago, reafirmando que la corrección quirúrgica del anillo vascular y un método de alimentación apropiado, permiten controlar la enfermedad a largo plazo. Se presenta la evolución clínica de la paciente durante 11 años, y los resultados de los estudios radiográficos realizados durante ese período.

A secondary megaesophagus, as a result of vascular ring anomalies, was diagnosed in a nine-week old female German Shepherd dog, with a history of intermittent regurgitation soon after weaning, respiratory disturbances, weight loss and growth retardation. A survey thoracic radiographs and a barium esophagogram confirmed the presence of a large esophageal dilatation cranial to the base of the heart, formed by three sacculations. A month later, the patient underwent a left intercostal thoracotomy to transect the ligamentum arteriosum to release the esophageal constriction. This procedure allowed to establish the definitive diagnosis of acquired secondary megaesophagus due to persistence of the fourth right aortic arch. After surgery, a feeding method was restarted in an upright position, with a soft diet, which was maintained with slight variations on a permanent basis. The patient showed a complete remission of clinical signs, despite the persistence of the megaesophagus, reaffirming that both the surgical correction of the vascular ring and an appropriate feeding method, help in controlling the disease in the long term. A report of the clinical evolution of the patient over 11 years and the results of radiographic studies conducted throughout this period are shown.