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Background The worldwide COVID-19 pandemic has initiated a change in medical education and the development of new teaching concepts has become inevitable to maintain adequate training. Objective This pilot study aims to compare teledidactic teaching with traditional face-to-face teaching for abdominal, thoracic, and thyroid ultrasound. Design Concurrently, a teledidactic and a face-to-face ultrasound course were held. The students completed seven 90-min modules using mobile ultrasound probes (Butterfly IQ). Each module consisted of a lecture, a demonstration of probe guidance, and independent training. Participants A total of thirty medical students took part in the study and were randomly assigned to a teledidactic and a face-to-face group. Main Measures An objective structured assessment of ultrasound skills (OSAUS) was performed as a pre-test and as the final exam and ultrasound images obtained during the exam were evaluated using the brightness mode quality ultrasound imaging examination (B-QUIET) scale. Key Results No significant difference between the two cohorts on the OSAUS final exam was shown ( p > 0.05 in all modules). There was a significant difference in the assessment of the images in the focused assessment with sonography for trauma (FAST) ( p 0.015) and aorta ( p 0.017) modules. Students in the teledidactic group performed better in both modules, scoring 33.59 (± 2.61) out of 44 in the module FAST (face-to-face group 30.95 (± 1.76)) and aortic images averaged 35.41 (± 2.61) points (face-to-face group 32.35 (± 3.08)). Conclusions A teledidactic course for abdominal and thoracic ultrasound examinations is equally effective to traditional face-to-face teaching in this pilot study. Digital implementation with a portable ultrasound machine could be a great opportunity to promote ultrasound education worldwide and over great distances.

The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR)=0.76, 95% confidence interval (95% CI) of 0.65-0.89, P=0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR=0.89, 95% CI: 0.74-1.08, P=0.24). The incidence of SPM were similar between the two arms (7% each, P=0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size [egs]10%) and renal impairment at baseline (serum creatinine >2 mg dl-1 ) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR=1.02, P=0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM.

Acute Graft-versus-host disease (GVHD) is a major immunological complication after allogeneic hematopoietic cell transplantation and a better understanding of the molecular regulation of the disease could help to develop novel targeted therapies. Here we found that a G/C polymorphism within the human microRNA-146a (miR-146a) gene of transplant recipients, which causes reduced miR-146a levels, was strongly associated with the risk of developing severe acute GVHD ( n =289). In mice, deficiency of miR-146a in the hematopoietic system or transfer of recipient-type miR-146a −/− dendritic cells (DCs) enhanced GVHD, while miR-146a mimic-transfected DCs ameliorated disease. Mechanistically, lack of miR-146a enhanced JAK2–STAT1 pathway activity, which led to higher expression of class II-transactivator (CIITA) and consecutively increased MHCII-levels on DCs. Inhibition of JAK1/2 or CIITA knockdown in DCs prevented miR-146a −/− DC-induced GVHD exacerbation. Consistent with our findings in mice, patients with the miR-146a polymorphism rs2910164 in hematopoietic cells displayed higher MHCII levels on monocytes, which could be targeted by JAK1/2 inhibition. Our findings indicate that the miR-146a polymorphism rs2910164 identifies patients at high risk for GVHD before allo-HCT. Functionally we show that miR-146a acts as a central regulator of recipient-type DC activation during GVHD by dampening the pro-inflammatory JAK–STAT/CIITA/MHCII axis, which provides a scientific rationale for early JAK1/2 inhibition in selected patients.

We evaluated the frequency, genetic architecture, clinico-pathologic features and prognostic impact of RUNX1 mutations in 2439 adult patients with newly-diagnosed acute myeloid leukemia (AML). RUNX1 mutations were found in 245 of 2439 (10%) patients; were almost mutually exclusive of AML with recurrent genetic abnormalities; and they co-occurred with a complex pattern of gene mutations, frequently involving mutations in epigenetic modifiers ( ASXL1 , IDH2 , KMT2A, EZH2 ), components of the spliceosome complex ( SRSF2 , SF3B1 ) and STAG2 , PHF6 , BCOR . RUNX1 mutations were associated with older age (16–59 years: 8.5%; ⩾60 years: 15.1%), male gender, more immature morphology and secondary AML evolving from myelodysplastic syndrome. In univariable analyses, RUNX1 mutations were associated with inferior event-free (EFS, P <0.0001), relapse-free (RFS, P =0.0007) and overall survival (OS, P <0.0001) in all patients, remaining significant when age was considered. In multivariable analysis, RUNX1 mutations predicted for inferior EFS ( P =0.01). The effect of co-mutation varied by partner gene, where patients with the secondary genotypes RUNX1 mut / ASXL1 mut (OS, P =0.004), RUNX1 mut / SRSF2 mut (OS, P =0.007) and RUNX1 mut / PHF6 mut (OS, P =0.03) did significantly worse, whereas patients with the genotype RUNX1 mut / IDH2 mut (OS, P =0.04) had a better outcome. In conclusion, RUNX1 -mutated AML is associated with a complex mutation cluster and is correlated with distinct clinico-pathologic features and inferior prognosis.

BackgroundQuality of life in patients suffering from rheumatological diseases is negatively affected by sleep disturbances, a frequently observed phenomenon. In rheumatoid arthritis, the prevalence of sleep disturbances ranges from about 50% to 70% [1]. The non-restorative sleep patterns result in excessive daytime sleepiness, reduced physical and mental performance, depression, and concentration disorders, as well as increased cardiovascular morbidity and risk of accidents [2].ObjectivesTo investigate the prevalence of sleep-related breathing disorders (SRBD), including obstructive and central sleep apnea (oSA, cSA), in patients with rheumatoid arthritis, psoriatic arthritis, and peripheral spondyloarthritis and to examine the relation between deterioration in sleep quality and selected clinical parameters.MethodsThis cross-sectional assessment consisted of a diagnostic workup, encompassing a questionnaire regarding sociodemographic characteristics, the assessment of arthritis disease activity using the Disease Activity Score (DAS28CRP), and the evaluation of daytime sleepiness using the Epworth Sleepiness Scale (ESS). Cardiorespiratory polygraphy (RPG) was performed to detect SRBD.ResultsA total of 54 patients (26 RA, 24 PsA, 4 pSpA) and 28 age- and gender-matched controls were recruited. The prevalence of sleep apnea in this study accounted for 39.7%, with a more than twofold higher presence of oSA than cSA. However, sleep apnea was diagnosed in approximately equal proportions of arthritis patients (39.5%) and controls (40.0%) (Figure 1). Male gender (p=0.013) and an increased age of approximately 55 years (p<0.001) were found to be significant risk factors for the presence of sleep apnea. Furthermore, differences, but without statistical significance, were found between subjects with sleep apnea and subjects without sleep apnea with respect to body mass index (p=0.085), positive smoking status (p=0.191), and arthritis disease activity as assessed by DAS28CRP (p=0.275). 42.3% of subjects affected by oSA or cSA showed excessive daytime sleepiness rated by ESS (p=0.024).ConclusionDespite the fact that the prevalence of SRBD in arthritis patients and controls is the same, physicians should be especially cautious of male patients over the age of 55. ESS score assessment helps to estimate the clinical risk. An early diagnosis of sleep apnea in arthritis patients may improve physical and psychological quality of life.References[1]Bourguignon C, Labyak SE, Taibi D. Investigating sleep disturbances in adults with rheumatoid arthritis. Holistic nursing practice 2003;17(5):241–49. https://pubmed.ncbi.nlm.nih.gov/14596374/.[2]Randerath W (2014). Schlafbezogene Atmungsstörungen: Obstruktive und zentrale Schlafapnoe. Springer Medizin Verlag GmbH & Springer Verlag GmbH, Teile von SpringerNature, 22 December 2014. Available at: https://www.springermedizin.de/emedpedia/dgim-innere-medizin/schlafbezogene-atmungsstoerungen-obstruktive-und-zentrale-schlafapnoe?epediaDoi=10.1007%2F978-3-642-54676-1_397 Accessed November 04, 2022.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundThe use of musculoskeletal ultrasound improves patient care by increasing diagnostic and therapeutic safety. With its growing application and increasing evidence of its value, the demand for standardized training in musculoskeletal ultrasonography (MSUS) rises rapidly.ObjectivesIn this systematic literature review, we aim to provide a general overview of the various aspects of musculoskeletal ultrasound education worldwide, including target groups, teaching staff, didactic methods, and course formats, as well as to reflect on existing problems and future opportunities. No restrictions were made regarding the educational level of the course recipients nor the specialization of the course instructors.MethodsIn our methodological approach, we followed the PRISMA statement for reporting systematic reviews and meta-analyses of studies[1]. In January 2022, the databases Embase, PubMed, and Google Scholar were considered with all publications to date and were filtered for relevant publications using previously defined keywords. Title and abstract were then screened independently by two authors for inclusion using relevant study characteristics determined in advance according to the PICO scheme[1]. Finally relevant information was filtered from the full text version of the sixty-seven included publications.ResultsThe range of training programs has increased greatly in recent years, primarily aiming at residents in rheumatology, radiology and physical medicine and rehabilitation. However, MSUS is also receiving more attention as a training tool for medical students. Due to the COVID pandemic, didactic approaches using distance learning via simulators and handheld devices have gained additional importance. Given the existing lack of sufficient equipment and trained teaching staff, those approaches should continue to be explored post-pandemic. Another still existing problem is the low international comparability of MSUS training and competency assessment. Therefore, several international institutions, including the European League Against Rheumatism (EULAR) and the Pan-American League of Associations for Rheumatology (PANLAR) have proposed guidelines for training curricula to promote standardized ultrasound training.ConclusionThere is a broad consensus that the development of standardized curricula improves training and facilitates the implementation of new training centers. The development of alternative teaching methods incorporating e-learning, peer teaching, and distance learning on mobile ultrasound devices and the determination of international guidelines could facilitate overcoming the remaining major obstacles still to be passed.Reference[1]Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009;339:b2700. doi:10.1136/bmj.b2700Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundPulmonary impairment in rheumatic diseases is a common, but poorly understood and deficient screened and managed extraarticular manifestation, which causes a huge increase in morbidity and mortality[1]. As previous studies focused on rheumatoid arthritis (RA) and in some intent on psoriatic arthritis (PsA), data for patients with peripheral spondyloarthritis (pSpA) is lacking.ObjectivesTo investigate the prevalence of clinical and subclinical pulmonary manifestations in newly diagnosed patients with RA, PsA, and pSpA and to compare different baseline examination results to develop a screening proposal for detecting patients at risk.MethodsThis clinical-prospective, longitudinal cohort study included a diagnostic workup consisting of a questionnaire for patient history, a physical examination, a body plethysmography with CO diffusion capacity (DLCO), a 6-minute walk test, laboratory parameters, and a chest x-ray (CXR) at the time of the initial diagnosis of arthritis disease, and at four additional time points in three-month intervals. This paper focuses on the baseline characteristics.Results54 outpatients (26 RA, 24 PsA, 4 pSpA) and 26 age- and gender-matched controls were examined. Pulmonary impairment, in the sense of a morphologically abnormal CXR, was diagnosed in 19 arthritis patients (38.0%). 36.8% of these suffered from clinical symptoms, such as cough and/or dyspnea. However, 63.2% presented subclinical, asymptomatic pulmonary abnormalities (see Figure 1). The baseline results of several examinations are illustrated in Table 1. An elevation of rheumatoid factor (> 14 IU/ml) showed an association with the manifestation of RA (p=0.002) as well as with the presence of pulmonary affection (p=0.008). In addition, the mean age of patients with pulmonary abnormalities (57.0 ± 12.8 yrs.) was different from that of patients without such abnormalities (43.9 ± 14.3 yrs.), with a p-value of 0.002. The association between the activity of arthritis disease, assessed by Disease Activity Score in 28 joints using CRP (DAS28CRP), and CXR findings proved to be significant (p=0.011). A DAS28CRP less than 3.2 (remission or low disease activity) indicated non-pathological findings in CXR.ConclusionThe prevalence of pulmonary manifestations was more than one-third, of which more than two-thirds presented asymptomatic. The large proportion of asymptomatic subjects highlights the need for the implementation of a pulmonary screening at the initial diagnosis of arthritis disease. By alerting physicians, especially in the observed age cohort of 57 years with elevated RF levels, morbidity and mortality could be reduced.Reference[1] Esposito AJ, Chu SG, Madan R, et al. Thoracic Manifestations of Rheumatoid Arthritis. Clinics in Chest Medicine 2019;40:545–60. doi:10.1016/j.ccm.2019.05.003Table 1.Findings in bodyplethysmography with CO diffusion capacity and laboratory parametersPresence of rheumatic diseasePresence of pulmonary disorders in chest x-rayRAa/PsAb/pSpAc (n=54)Control proband (n=26)Present (n=19)Not present (n=31)Restrictive lung diseaseNot present3916152184.8%64.0%88.2%84.0%Present(FVC < 70%; TLC < 80%)792415.2%36.0%11.8%16.0%Obstructive lung diseaseNot present46251725100.0%100.0%100.0%100.0%Present(FEV1/FVC < 70%)00000.0%0.0%0.0%0.0%EmphysemaNot present3919142386.7%76.0%82.4%95.8%Present(RV > 140%)663113.3%24.0%17.6%4.2%Diffusion disturbanceNot present3721132186.0%91.3%81.3%91.3%Present(DLCO < 60%)623214.0%8.7%18.8%8.7%C-reactive proteinNon-pathological(≤ 3 mg/l)191941335.2%86.4%21.1%41.9%Pathological(> 3 mg/l)353151864.8%13.6%78.9%58.1%Rheumatoid factorNon-pathological(≤ 14 IU/ml)311962166.0%95.0%37.5%77.8%Pathological(> 14 IU/ml)16110634.0%5.0%62.5%22.2%PsA – psoriatic arthritis, RA – rheumatoid arthritis, pSpA – peripheral spondyloarthritisAcknowledgements:NIL.Disclosure of InterestsNone Declared.

Proteasome inhibitors are emerging as effective drugs for the treatment of multiple myeloma and possibly certain subtypes of non-Hodgkin's lymphoma. Bortezomib (Velcade) is the first proteasome inhibitor proven to be clinically useful and will soon be followed by a second generation of small molecule inhibitors with improved pharmacological properties. Although it is now understood that certain types of malignancies have an exquisite dependence on a functional proteasome for their survival, the underlying reason(s) remain unclear as of now. In this context, addiction to nuclear factor- κ B (NF- κ B)-induced survival signals, activation of the unfolded protein response as well as a reduced proteasomal activity in differentiated plasma cells have all been proposed to justify proteasome inhibitors' activity in susceptible tissues. In addition to their anticancer properties, bortezomib and related drugs modulate inflammatory and immune responses by affecting function and survival of immune cells such as lymphocytes and dendritic cells. The present review offers an overview of the biological effects that have been involved in proteasome inhibitors' antitumor activity and suggests prospective future applications for these drugs based on their recently characterized anti-inflammatory and immunomodulatory effects.

We describe genetic and clinical characteristics of acute myeloid leukemia (AML) patients according to age from an academic population-based registry. Adult patients with newly diagnosed AML at 63 centers in Germany and Austria were followed within the AMLSG BiO registry (NCT01252485). Between January 1, 2012, and December 31, 2014, data of 3525 patients with AML (45% women) were collected. The median age was 65 years (range 18–94). The comparison of age-specific AML incidence rates with epidemiological cancer registries revealed excellent coverage in patients < 70 years old and good coverage up to the age of 80. The distribution according to the European LeukemiaNet (ELN) risk categorization from 2010 was 20% favorable, 31% intermediate-1, 28% intermediate-2, and 21% adverse. With increasing age, the relative but not the absolute prevalence of patients with ELN favorable and intermediate-1 risk ( p  < 0.001), with activating FLT3 mutations ( p  < 0.001), with ECOG performance status < 2 ( p  < 0.001), and with HCT-CI comorbidity index < 3 ( p  < 0.001) decreased. Regarding treatment, obesity and favorable risk were associated with an intensive treatment, whereas adverse risk, higher age, and comorbidity index > 0 were associated with non-intensive treatment or best supportive care. The AMLSG BiO registry provides reliable population-based distributions of genetic, clinical, and treatment characteristics according to age.