Early referral of patients with suspected polymyalgia rheumatica - A systematic review.

INTRODUCTION: Prompt diagnosis and treatment of polymyalgia rheumatica (PMR) is crucial to prevent long-term complications and improve patient outcomes. However, there is currently no standardized approach to referral of suspected PMR patients to rheumatologists, leading to inconsistent management practices. The objective of this systematic review was to clarify the existing evidence regarding the following aspects of early management strategies in patients with suspected PMR: diagnostic strategies, GCA screening, glucocorticoid initiation prior to referral, value of shared care and value of fast track clinic. METHODS: Two authors performed a systematic literature search, data extraction and risk of bias assessment independently. The literature search was conducted in Embase, MEDLINE (PubMed) and Cochrane. Studies were included if they contained cohorts of suspected PMR patients and evaluated the efficacy of different diagnostic strategies for PMR, screening for giant cell arteritis (GCA), starting glucocorticoids before referral to secondary care, shared care, or fast-track clinics. RESULTS: From 2,437 records excluding duplicates, 14 studies met the inclusion criteria. Among these, 10 studies investigated the diagnostic accuracy of various diagnostic strategies with the majority evaluating different clinical approaches, but none of them showed consistently high performance. However, 4 studies on shared care and fast-track clinics showed promising results, including reduced hospitalization rates, lower starting doses of glucocorticoids, and faster PMR diagnosis. CONCLUSION: This review emphasizes the sparse evidence of early management and referral strategies for patients with suspected PMR. Additionally, screening and diagnostic strategies for differentiating PMR from other diseases, including concurrent GCA, require clarification. Fast-track clinics may have potential to aid patients with PMR in the future, but studies will be needed to determine the appropriate pre-referral work-up.

Remission and low disease activity in Polish patients with systemic lupus erythematosus - real-life, five-year follow-up outcomes.

OBJECTIVE: Remission in systemic lupus erythematosus (SLE) or Lupus Low Disease Activity State (LLDAS) are associated with less organ damage and thus create new perspectives for effective damage-limiting treatment. The aim of this study was to assess the occurrence of remission defined by The Definition of Remission In SLE (DORIS) and of LLDAS as well as their predictors in the Polish SLE cohort. PATIENTS AND METHODS: In this retrospective study data were collected on patients with SLE that achieved at least one year of DORIS remission or LLDAS and were followed up for 5 years. Clinical and demographic data were gathered; DORIS and LLDAS predictors were determined by univariate regression analysis. RESULTS: The full analysis set included 80 patients at baseline and 70 at follow-up. Over half of patients with SLE (39; 55.7%) fulfilled the DORIS remission criteria. In this group, 53.8% (21) of patients were in remission on-treatment and 46.1% (18) in remission off-treatment. LLDAS was fulfilled by a cohort of 43 (61.4%) patients with SLE. Among patients that achieved DORIS or LLDAS at follow-up, 77% were not treated with glucocorticoids (GCs). The most important predictors for DORIS and LLDAS off-treatment were mean SLEDAI-2K score with cut-off of ≤8.0, treatment with mycophenolate mofetil or antimalarials, and the age at disease onset above 43 years. CONCLUSIONS: Remission and LLDAS are achievable goals in treating SLE as over half of study patients fulfilled the DORIS remission and LLDAS criteria. The identified predictors for DORIS and LLDAS indicate the importance of effective therapy leading to reduction of GC use.

Characterization data of reference materials used for phase II of the priority program DFG SPP 2005 "Opus Fluidum Futurum - Rheology of reactive, multiscale, multiphase construction materials".

A thorough characterization of base materials is the prerequisite for further research. In this paper, the characterization data of the reference materials (CEM I 42.5 R, limestone powder, calcined clay and a mixture of these three components) used in the second funding phase of the priority program 2005 of the German Research Foundation (DFG SPP 2005) are presented under the aspects of chemical and mineralogical composition as well as physical and chemical properties. The data were collected based on tests performed by up to eleven research groups involved in this cooperative program.

Development and validation of COVID-19 Radiological Risk Score (COVID-RRS): a multivariable radiological score to estimate the in-hospital mortality risk in COVID-19 patients.

OBJECTIVE: To develop and validate in-hospital mortality risk score comprising radiological aberrances in chest computed tomography (CT) performed on admission. PATIENTS AND METHODS: Single-center, longitudinal cohort study in adult patients admitted with Coronavirus Disease 2019 (COVID-19) to our ward. Patients were followed-up during hospitalization until discharge or death. Eligibility criteria for the study comprised positive real-time reverse transcription-polymerase chain reaction test (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ground-glass opacities in chest CT. In-hospital death was the outcome of interest. Radiological, laboratory, and clinical data were analyzed. Radiological determinants of mortality were used as variables in multivariate logistic regression analysis, and results were used to build a radiological risk score. RESULTS: 371 patients were enrolled in development and validation cohorts (181 and 190 respectively), with a total of 47 non-survivors. Univariate analysis data determined 12 predictive factors (nine risk and three protective). In multivariate analysis, we developed COVID-RRS (COVID-19 Radiological Risk Score) - a radiological score predicting in-hospital COVID-19 mortality risk comprising estimated lung involvement percentage, pleural effusion, and domination of consolidation-type changes in chest CT. Our score was superior in the prediction of COVID-19 mortality to the percentage of lung involvement alone, Chest Computed Tomography Severity Score (CTSS), and Total Severity Score (TSS) in both groups with AUC of 0.910 and 0.902, respectively (p <0.001). CONCLUSIONS: Additional imaging features independently contribute to COVID-19 mortality risk. Our model comprising lung involvement estimation, pleural effusion, and domination of consolidations performed significantly better than scores based on the extent of the changes alone. COVID-RRS is a simple, reliable, and ready-to-use tool for clinical practice.

Active Learning: Action Potential and Clinical Applications in Neuroscience Medical Education.

Active learning in medical education engages adult learners and increases collaborative opportunities for consolidation of concepts. An innovative learning activity was used to engage medical students in an activity about action potentials and its clinical applications, resulting in increased understanding, application, and retention of the clinical relevance of the topic.

Association of ultrasound-confirmed axillary artery vasculitis and clinical outcomes in giant cell arteritis.

OBJECTIVES: The aim of this observational study was to compare clinical outcomes including glucocorticoid treatment and relapses between giant cell arteritis (GCA) patients with (axGCA) and without axillary artery involvement (non-axGCA). METHODS: Axillary artery ultrasound was performed in 101 GCA patients at multiple time points. Patients with signs of vasculitis of the axillary arteries at baseline were compared to patients without signs of axillary artery involvement. Cumulative GC doses and relapse rates were calculated as well as survival curves to compare the time until GC discontinuation and occurrence of the first clinical relapse. A linear mixed model was used to assess the effect of a clinical relapse on the intima media thickness (IMT) in axGCA patients. RESULTS: Sixty-seven patients were classified as axGCA, 34 as non-axGCA patients. Compared with non-axGCA, axGCA patients yielded a higher (albeit not significant) median time until GC discontinuation (42 months (95% CI: 33-84) vs 30 months (95% CI: 21-42), p=0.060) and median cumulative GC dose (6801mg (range 1748-34169) vs 5633mg (range: 2553-19967), p=0.051). Time until the first relapse (axGCA: 12 months (95% CI: 8-42) vs non-axGCA: 13.5 months (95% CI: 6-27), p=0522) and relapse rates (2 (range: 0-16) vs 1 (range: 0-13), p=0.67) were similar in both groups. Relapses resulted in an increase of the IMT by 0.18mm (95% CI: 0.07-0.30, p=0.003). CONCLUSION: Patients with axGCA have a trend towards longer treatment duration and higher GC requirements as compared to non-axGCA patients. A relapse leads to an increase of the IMT by 0.18mm.

A recurrent single-amino acid deletion (p.Glu500del) in the head domain of ß-cardiac myosin in two unrelated boys presenting with polyhydramnios, congenital axial stiffness and skeletal myopathy.

BACKGROUND: Alterations in the MYH7 gene can cause cardiac and skeletal myopathies. MYH7-related skeletal myopathies are extremely rare, and the vast majority of causal variants in the MYH7 gene are predicted to alter the rod domain of the of ß-cardiac myosin molecule, resulting in distal muscle weakness as the predominant manifestation. Here we describe two unrelated patients harboring an in-frame deletion in the MYH7 gene that is predicted to result in deletion of a single amino acid (p.Glu500del) in the head domain of ß-cardiac myosin. Both patients display an unusual skeletal myopathy phenotype with congenital axial stiffness and muscular hypertonus, but no cardiac involvement. RESULTS: Clinical data, MRI results and histopathological data were collected retrospectively in two unrelated boys (9 and 3.5 years old). Exome sequencing uncovered the same 3-bp in-frame deletion in exon 15 (c.1498_1500delGAG) of the MYH7 gene of both patients, a mutation which deletes a highly conserved glutamate residue (p.Glu500del) in the relay loop of the head domain of the ß-cardiac myosin heavy chain. The mutation occurred de novo in one patient, whereas mosaicism was detected in blood of the father of the second patient. Both boys presented with an unusual phenotype of prenatal polyhydramnios, congenital axial stiffness and muscular hypertonus. In one patient the phenotype evolved into an axial/proximal skeletal myopathy without distal involvement or cardiomyopathy, whereas the other patient exhibited predominantly stiffness and respiratory involvement. We review and compare all patients described in the literature who possess a variant predicted to alter the p.Glu500 residue in the ß-cardiac myosin head domain, and we provide in-silico analyses of potential effects on polypeptide function. CONCLUSION: The data presented here expand the phenotypic spectrum of mutations in the MYH7 gene and have implications for future diagnostics and therapeutic approaches.

A cluster-randomised trial to evaluate an intervention to promote handwashing in rural Nigeria.

Handwashing with soap at critical times helps prevent diarrhoeal diseases. Changing handwashing practices through behaviour change communication remains a challenge. This study designed and tested a scalable intervention to promote handwashing with soap. A cluster-randomised, controlled trial compared our intervention against standard practice. Subjects were men, women and children in 14 villages in Cross-River state, Nigeria. The primary outcome was the proportion of observed key events on which hands were washed with soap. Binomial regression analysis calculated prevalence differences between study arms. The intervention had minimal effect on the primary outcome (+2.4%, p = 0.096). The intervention was associated with increased frequency of handwashes without soap before food contact (+13%, p = 0.017). The intervention failed to produce significant changes in handwashing with soap at key times. The low dose delivered (two contact points) may have increased scalability at the cost of effectiveness, particularly in the challenging context of inconvenient water access.

A study on echocardiographic findings in hospitalized patients with connective tissue diseases.

OBJECTIVE: To determine the prevalence of echocardiographic findings and their change over time in patients with connective tissue diseases (CTDs) and to analyse which findings were associated with escalation of immunosuppressive therapy. METHOD: We conducted a retrospective cohort study of consecutive hospitalized patients from a tertiary rheumatology referral centre who received transthoracic echocardiography between 1 January 2006 and 31 December 2015. We tested for associations between echocardiographic findings and treatment escalation via Fisher's exact test; p < 0.05 was considered significant. Escalation of therapy was defined by dosage of glucocorticoids and type of disease-modifying anti-rheumatic drug. The clinical relevance of echocardiographic findings concerning change in immunosuppressive therapy was recorded. RESULTS: In total, 1004 patients were included (865 females), with a total of 1660 echocardiographic examinations. The most frequent findings were mitral, tricuspid, and aortic valve regurgitation (found in 36.7%, 25.4%, and 17.7% of all patients), aortic valve sclerosis (20.1%), left ventricular dysfunction (21.5%), and left atrial dilatation (19.2%). Only pericardial effusions were more frequent in cases with treatment escalation (10.9% of cases with escalated therapy vs 6.9% of cases without, p = 0.007). In 314 patients who received follow-up examinations, echocardiographic findings were found to change between examinations. Only 73 of all 1660 examinations were discussed in depth considering the treatment strategy in the hospital discharge letter. CONCLUSION: Patients with CTDs exhibited a wide, dynamically changing spectrum of echocardiographic abnormalities. Most findings neither reflected disease activity nor appeared to influence the therapeutic regimen.

Utilizing optical spectroscopy and 2',7'-difluorofluorescein to characterize the early stages of cement hydration.

The increasingly sophisticated nature of modern, more environmentally friendly cementitious binders requires a better understanding and control particularly of the complex, dynamic processes involved in the early phase of cement hydration. In-situ monitoring of properties of a constantly changing system over a defined period of time calls for simple, sensitive, fast, and preferably also non-invasive methods like optical spectroscopy. Here, we exploit the time-dependent changes in the absorbance and fluorescence features of the negatively charged optical probe 2',7'-difluorofluorescein (DFFL) for the study of the hydration processes in pastes of white cement (WC), cubic tricalcium aluminate (C3A), and tricalcium silicate (C3S), the main phases of cement, and in pastes of quartz (Q) over 24 h after addition of the dye solution. For comparison, also conventional techniques like isothermal heat flow calorimetry were applied. Based upon the time-dependent changes in the spectroscopic properties of DFFL, that seem to originate mainly from dye aggregation and dye-surface interactions and considerably vary between the different pastes, molecular pictures of the hydration processes in the cement pastes are derived. Our results clearly demonstrate the potential of optical spectroscopy, i.e., diffuse reflectance, steady state and time-resolved fluorometry in conjunction with suitable optical reporters, to probe specific hydration processes and to contribute to a better understanding of the early hydration processes of cement at the molecular scale.

Charge disproportionation and nano phase separation in [Formula: see text].

We have successfully grown centimeter-sized layered [Formula: see text] single crystals under high oxygen pressures of 120-150 bar by the floating zone technique. This enabled us to perform neutron scattering experiments where we observe close to quarter-integer magnetic peaks below [Formula: see text] that are accompanied by steep upwards dispersing spin excitations. Within the high-frequency Ni-O bond stretching phonon dispersion, a softening at the propagation vector for a checkerboard modulation can be observed. We were able to simulate the magnetic excitation spectra using a model that includes two essential ingredients, namely checkerboard charge disproportionation and nano phase separation. The results thus suggest that charge disproportionation is preferred instead of a Jahn-Teller distortion even for this layered [Formula: see text] system.

Vibration-Driven Self-Doping of Dangling-Bond Wires on Si(553)-Au Surfaces.

Density-functional theory is used to explore the Si(553)-Au surface dynamics. Our study (i) reveals a complex two-stage order-disorder phase transition where with rising temperature first the ×3 order along the Si step edges and, subsequently, the ×2 order of the Au chains is lost, (ii) identifies the transient modification of the electron chemical potential during soft Au chain vibrations as instrumental for disorder at the step edge, and (iii) shows that the transition leads to a self-doping of the Si dangling-bond wire at the step edge. The calculations are corroborated by Raman measurements of surface phonon modes and explain previous electron diffraction, scanning tunneling microscopy, and surface transport data.

Characterization data of reference cement CEM III/A 42.5N used for priority program DFG SPP 2005 "Opus Fluidum Futurum - Rheology of reactive, multiscale, multiphase construction materials".

Two types of cements were selected as the reference cement in the priority program 2005 of the German Research Foundation (DFG SPP 2005). A thorough characterization of CEM I 42.5 R has been made in a recent publication [1]. In this paper, the characterization data of the other reference cement CEM III/A 42.5 N are presented from the aspects of chemical and mineralogical compositions as well as physical and chemical properties. The characterization data of the slag, which is the second main constituent of this specific cement besides the clinker, are presented independently. For all data received, the mean values and the corresponding errors were calculated. The data shall be used for the ongoing research within the priority program. Also, researchers from outside this priority program can benefit from these data if the same materials are used.

A photoredox catalysed Heck reaction via hole transfer from a Ru(ii)-bis(terpyridine) complex to graphene oxide.

The attachment of homoleptic Ru bis-terpy complexes on graphene oxide significantly improved the photocatalytic activity of the complexes. These straightforward complexes were applied as photocatalysts in a Heck reaction. Due to covalent functionalization on graphene oxide, which functions as an electron reservoir, excellent yields were obtained. DFT investigations of the charge redistribution revealed efficient hole transfer from the excited Ru unit towards the graphene oxide.

Characterization data of reference cement CEM I 42.5 R used for priority program DFG SPP 2005 "Opus Fluidum Futurum - Rheology of reactive, multiscale, multiphase construction materials".

A thorough characterization of starting materials is the precondition for further research, especially for cement, which contains various phases and presents quite a complex material for fundamental scientific investigation. In the paper at hand, the characterization data of the reference cement CEM I 42.5 R used within the priority program 2005 of the German Research Foundation (DFG SPP 2005) are presented from the aspects of chemical and mineralogical compositions as well as physical and chemical properties. The data were collected based on tests conducted by nine research groups involved in this cooperative program. For all data received, the mean values and the corresponding errors were calculated. The results shall be used for the ongoing research within the priority program.

[Imaging diagnostics in large vessel vasculitis]. / Bildgebende Diagnostik bei Großgefäßvaskulitiden.

Imaging procedures have become an important diagnostic tool in vasculitis. In large vessel vasculitides, such as giant-cell arteritis (GCA) and Takayasu arteritis, ultrasound, magnetic resonance imaging (MRI), computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) can depict specific abnormalities of the arterial wall. A clinically suspected diagnosis can be confirmed by imaging if performed by a trained specialist using appropriate equipment, without histological investigations. Ultrasound, MRI and CT show a homogeneous, concentric thickening of the arterial wall and PET can detect increased glucose metabolism of the arterial wall. Ultrasound is the method of choice, especially in predominantly cranial GCA. Imaging should be performed before or within the first few days of glucocorticoid treatment as the PET findings of all arteries as well as ultrasound and MRI findings in temporal arteries normalize quickly with treatment. A planned imaging examination must not delay initiation of glucocorticoid treatment.