Teaching ultrasound in a curricular course according to certified EFSUMB standards during undergraduate medical education: a prospective study

Background: As a non-invasive and readily available diagnostic tool, ultrasound is one of the most important imaging techniques in medicine. Ultrasound is usually trained during residency preferable according to German Society of Ultrasound in Medicine (DEGUM) standards. Our curriculum calls for undergraduate training in ultrasound of medical students in their 4th year of undergraduate education. An explorative pilot study evaluated the acceptance of this teaching method, and compared it to other practical activities in medical education at Muenster University. Methods: 240 medical students in their 4th year of undergraduate medical education participated in the training and completed a pre- and post-questionnaire for self-assessment of technical knowledge, self-assurance of the procedure, and motivation in performing ultrasound using a Likert scale. Moreover, students were asked about their interest in pursuing a career in internal medicine. To compare this training to other educational activities a standardized online evaluation tool was used. A direct observation of procedural skills assessment (DOPS) for the first time applied on ultrasound aimed to independently assess the success of our teaching method. Results: There was a significant increase in technical knowledge and self-assurance (p < 0.001) of the students’ self-assessments. The clinical relevance and self-motivation of the teaching were evaluated positively. The students’ DOPS results demonstrated proficiency in the understanding of anatomic structures shown in ultrasonographic images, including terminology, machine settings, and transducer frequencies. Conclusions: Training ultrasound according to certified DEGUM standards was successful and should be offered in undergraduate medical education. The evaluation of the course affirmed the necessity, quality and clinical relevance of the course with a top ranking score of hands-on training courses within the educational activities of the Medical Faculty of Muenster.<br

K(2P)18.1 translates T cell receptor signals into thymic regulatory T cell development

It remains largely unclear how thymocytes translate relative differences in T cell receptor (TCR) signal strength into distinct developmental programs that drive the cell fate decisions towards conventional (Tconv) or regulatory T cells (Treg). Following TCR activation, intracellular calcium (Ca2+) is the most important second messenger, for which the potassium channel K(2P)18.1 is a relevant regulator. Here, we identify K(2P)18.1 as a central translator of the TCR signal into the thymus-derived Treg (tTreg) selection process. TCR signal was coupled to NF-kappa B-mediated K(2P)18.1 upregulation in tTreg progenitors. K(2P)18.1 provided the driving force for sustained Ca2+ influx that facilitated NF-kappa B- and NFAT-dependent expression of FoxP3, the master transcription factor for Treg development and function. Loss of K(2P)18.1 ion-current function induced a mild lymphoproliferative phenotype in mice, with reduced Treg numbers that led to aggravated experimental autoimmune encephalomyelitis, while a gain-of-function mutation in K(2P)18.1 resulted in increased Treg numbers in mice. Our findings in human thymus, recent thymic emigrants and multiple sclerosis patients with a dominant-negative missense K(2P)18.1 variant that is associated with poor clinical outcomes indicate that K(2P)18.1 also plays a role in human Treg development. Pharmacological modulation of K(2P)18.1 specifically modulated Treg numbers in vitro and in vivo. Finally, we identified nitroxoline as a K(2P)18.1 activator that led to rapid and reversible Treg increase in patients with urinary tract infections. Conclusively, our findings reveal how K(2P)18.1 translates TCR signals into thymic T cell fate decisions and Treg development, and provide a basis for the therapeutic utilization of Treg in several human disorders.Peer reviewe

Risk factors for severe outcomes for COVID-19 patients hospitalised in Switzerland during the first pandemic wave, February to August 2020: prospective observational cohort study.

As clinical signs of COVID-19 differ widely among individuals, from mild to severe, the definition of risk groups has important consequences for recommendations to the public, control measures and patient management, and needs to be reviewed regularly. The aim of this study was to explore risk factors for in-hospital mortality and intensive care unit (ICU) admission for hospitalised COVID-19 patients during the first epidemic wave in Switzerland, as an example of a country that coped well during the first wave of the pandemic. This study included all (n = 3590) adult polymerase chain reaction (PCR)-confirmed hospitalised patients in 17 hospitals from the hospital-based surveillance of COVID-19 (CH-Sur) by 1 September 2020. We calculated univariable and multivariable (adjusted) (1) proportional hazards (Fine and Gray) survival regression models and (2) logistic regression models for in-hospital mortality and admission to ICU, to evaluate the most common comorbidities as potential risk factors. We found that old age was the strongest factor for in-hospital mortality after having adjusted for gender and the considered comorbidities (hazard ratio [HR] 2.46, 95% confidence interval [CI] 2.33&amp;minus;2.59 and HR 5.6 95% CI 5.23&amp;minus;6 for ages 65 and 80 years, respectively). In addition, male gender remained an important risk factor in the multivariable models (HR 1.47, 95% CI 1.41&amp;minus;1.53). Of all comorbidities, renal disease, oncological pathologies, chronic respiratory disease, cardiovascular disease (but not hypertension) and dementia were also risk factors for in-hospital mortality. With respect to ICU admission risk, the pattern was different, as patients with higher chances of survival might have been admitted more often to ICU. Male gender (OR 1.91, 95% CI 1.58&amp;minus;2.31), hypertension (OR&amp;nbsp; 1.3, 95% CI 1.07&amp;minus;1.59) and age 55&amp;ndash;79 years (OR 1.15, 95% CI 1.06&amp;minus;1.26) are risk factors for ICU admission. Patients aged 80+ years, as well as patients with dementia or with liver disease were admitted less often to ICU. We conclude that increasing age is the most important risk factor for in-hospital mortality of hospitalised COVID-19 patients in Switzerland, along with male gender and followed by the presence of comorbidities such as renal diseases, chronic respiratory or cardiovascular disease, oncological malignancies and dementia. Male gender, hypertension and age between 55 and 79 years are, however, risk factors for ICU admission. Mortality and ICU admission need to be considered as separate outcomes when investigating risk factors for pandemic control measures and for hospital resources planning

K18.1 translates T cell receptor signals into thymic regulatory T cell development.

It remains largely unclear how thymocytes translate relative differences in T cell receptor (TCR) signal strength into distinct developmental programs that drive the cell fate decisions towards conventional (Tconv) or regulatory T cells (Treg). Following TCR activation, intracellular calcium (Ca2+) is the most important second messenger, for which the potassium channel K2P18.1 is a relevant regulator. Here, we identify K2P18.1 as a central translator of the TCR signal into the thymus-derived Treg (tTreg) selection process. TCR signal was coupled to NF-κB-mediated K2P18.1 upregulation in tTreg progenitors. K2P18.1 provided the driving force for sustained Ca2+ influx that facilitated NF-κB- and NFAT-dependent expression of FoxP3, the master transcription factor for Treg development and function. Loss of K2P18.1 ion-current function induced a mild lymphoproliferative phenotype in mice, with reduced Treg numbers that led to aggravated experimental autoimmune encephalomyelitis, while a gain-of-function mutation in K2P18.1 resulted in increased Treg numbers in mice. Our findings in human thymus, recent thymic emigrants and multiple sclerosis patients with a dominant-negative missense K2P18.1 variant that is associated with poor clinical outcomes indicate that K2P18.1 also plays a role in human Treg development. Pharmacological modulation of K2P18.1 specifically modulated Treg numbers in vitro and in vivo. Finally, we identified nitroxoline as a K2P18.1 activator that led to rapid and reversible Treg increase in patients with urinary tract infections. Conclusively, our findings reveal how K2P18.1 translates TCR signals into thymic T cell fate decisions and Treg development, and provide a basis for the therapeutic utilization of Treg in several human disorders