Enriched human embryonic stem cells-derived CD133+, CD24+ renal progenitors engraft and restore function in a gentamicin-induced kidney injury in mice.

Introduction: Acute kidney injury (AKI) is a common health problem that leads to high morbidity and potential mortality. The failure of conventional treatments to improve forms of this condition highlights the need for innovative and effective treatment approaches. Regenerative therapies with Renal Progenitor Cells (RPCs) have been proposed as a promising new strategy. A growing body of evidence suggests that progenitor cells differentiated from different sources, including human embryonic stem cells (hESCs), can effectively treat AKI. Methods: Here, we describe a method for generating RPCs and directed human Embryoid Bodies (EBs) towards CD133+CD24+ renal progenitor cells and evaluate their functional activity in alleviating AKI. Results: The obtained results show that hESCs-derived CD133+CD24+ RPCs can engraft into damaged renal tubules and restore renal function and structure in mice with gentamicin-induced kidney injury, and significantly decrease blood urea nitrogen levels, suppress oxidative stress and inflammation, and attenuate histopathological disturbances, including tubular necrosis, tubular dilation, urinary casts, and interstitial fibrosis. Conclusion: The results suggest that RPCs have a promising regenerative potential in improving renal disease and can lay the foundation for future cell therapy and disease modeling.

[Significance of phosphate in internal medicine]. / Phosphat in der Inneren Medizin.

Phosphate is essential for bone metabolism and for energy provision. Phosphate homeostasis is achieved by hormonal feedback mechanisms, predominantly parathyroid hormone, fibroblast growth factor 23 and calcitriol, with renal phosphate absorption taking on a special role. Although even large deviations from the serum normal range are rarely symptomatic, the health consequences can be significant. Essentially, the clinically relevant disturbances in phosphate balance can be attributed to three mechanisms: 1. shifts of phosphate between the extracellular space and the cytosol; 2. inadequate phosphate reabsorption in the kidney; 3. decreased intestinal phosphate absorption. Knowledge of physiology enables diagnosis and therapy of phosphate disorders.

Near-peer compared to faculty teaching of abdominal ultrasound for medical students - A randomized-controlled trial.

PURPOSE: Medical schools increasingly rely on near-peer tutors for ultrasound teaching. We set out to compare the efficacy of a blended near-peer ultrasound teaching program to that of a faculty course in a randomized controlled trial. METHODS: 152 medical students received 21 hours of ultrasound teaching either by near-peer teachers or medical doctors. The near-peer course consisted of blended learning that included spaced repetition. The faculty-led course was the European common course for abdominal sonography. The primary outcome measurement was the students' ultrasound knowledge at month 6, assessed by structured examination (score 0 to 50). Secondary outcomes included scores at month 0 and changes in scores after the course. RESULTS: Students in the near-peer group scored 37 points, and students in the faculty group scored 31 points six months after course completion. The difference of 5.99 points (95% CI 4.48;7.49) in favor of the near-peer group was significant (p<0.001). Scores immediately after the course were 3.8 points higher in the near-peer group (2.35; 5.25, p<0.001). Ultrasound skills decreased significantly in the six months after course completion in the faculty group (-2.41 points, [-3.39; -1.42], p<0.001]) but barely decreased in the near-peer group (-0.22 points, [-1.19; 0.75, p=0.66]). CONCLUSION: The near-peer course that combined blended learning and spaced repetition outperformed standard faculty teaching in basic ultrasound education. This study encourages medical schools to use peer teaching combined with e-learning and spaced repetition as an effective means to meet the increasing demand for ultrasound training.

Rosuvastatin-induced rhabdomyolysis: case report and call for proactive multifactorial risk assessment and preventive management of statin therapy in high-risk patients.

Cholesterol-lowering statins are frequently prescribed for primary and secondary prevention of ischaemic vascular events. Whereas most patients tolerate statins without problems, statin-associated myopathy is well documented, as are several risk factors. We present a case report of an 80-90-year-old man with coronary artery disease who rapidly developed severe rhabdomyolysis during treatment with rosuvastatin while in intensive care. He had several concomitant risk factors for statin-induced myopathy including high dosage, old age, renal and hepatic impairment, and a pharmacogenetic SLCO1B1*1 a/*5 variant. Single known risk factors have a low predictive value for statin-induced myopathy and may therefore be underestimated in clinical practice. However, adverse drug reactions frequently involve the joint action of a multitude of environmental and genetic component causes, and statin-induced myopathy should be regarded as a multicausal event. We therefore advocate a proactive multifactorial risk assessment to guide and individualise statin therapy in high-risk patients.

[Perspectives and Challenges of hand-held Ultrasound]. / Entwicklungen, Herausforderung und Perspektiven des Handheld-Ultraschalls (HHUS).

The use of handheld ultrasound devices from a technical and data protection point of view, device properties, functionality, documentation, indications, delegation of performance, applications by doctors, students and non-medical staff is examined and discussed.

Recombinant ADAMTS13 for Hereditary Thrombotic Thrombocytopenic Purpura.

A 27-year-old patient with a history of severe obstetrical complications and arterial thrombosis received a diagnosis of hereditary thrombotic thrombocytopenic purpura (TTP) due to severe ADAMTS13 deficiency when she presented with an acute episode in the 30th week of her second pregnancy. When the acute episode of hereditary TTP became plasma-refractory and fetal death was imminent, weekly injections of recombinant ADAMTS13 at a dose of 40 U per kilogram of body weight were initiated. The patient's platelet count normalized, and the growth of the fetus stabilized. At 37 weeks 1 day of gestation, a small-for-gestational-age boy was delivered by cesarean section. At the time of this report, the patient and her son were well, and she continued to receive injections of recombinant ADAMTS13 every 2 weeks. (Funded by the Swiss National Science Foundation.).

Cost-Effectiveness of Treating Patients with Chronic Kidney Disease and Prior Hyperkalemia with Renin-Angiotensin-Aldosterone System Inhibitor and Patiromer: A Swiss Public Healthcare Perspective.

INTRODUCTION: Hyperkalemia is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD). Patiromer (Veltassa®) is an oral potassium binder indicated for the treatment of hyperkalemia in adults. We evaluated the impact of patiromer on the Swiss healthcare resources when used in patients with CKD and hyperkalemia who were on renin-angiotensin-aldosterone system inhibitor (RAASi) treatment. METHODS: We built a decision tree and calculated the number needed to treat (NNT) to prevent hyperkalemia, hospitalization, and death based on published aggregated data. The decision tree was populated with available data from relevant patiromer clinical trials and data were applied to create a simple model showing the expected effectiveness of adding patiromer to the treatment of patients with medium-to-severe stage CKD on RAASi compared to RAASi only. Adapting the model to the Swiss healthcare system allowed us to estimate the impact of the new treatment on healthcare expenditures from a payer as well as a Swiss public healthcare perspective. RESULTS: Patiromer reduced the absolute risk for recurrent hyperkalemia by 48% within 8 weeks, resulting in an NNT of 2.1 [95% CI 1.4, 3.7]. If one assumes that 90%, 50%, or 10% of all moderate-to-severe hyperkalemic events lead to hospitalization, the NNT to prevent one hospitalization would be 2.5, 4.4, and 22.2, respectively. On the basis of the death rate of patients with mild or moderate-to-severe hyperkalemia, and the prevalence of mild or moderate-to-severe hyperkalemia in the treatment and control groups, the NNT was 78.7 [95% CI 64.0, 99.3] to prevent one death. Patiromer resulted in expected cost offsets of CHF 303 (1 CHF = 0.95 EUR as of 2022) per patient over 8 weeks in Switzerland. CONCLUSION: Patiromer used for the treatment of CKD reduces hyperkalemia recurrence leading to improved patient care. This results in substantial offset costs for the Swiss healthcare system.

Clinical Relevance of a 16-Gene Pharmacogenetic Panel Test for Medication Management in a Cohort of 135 Patients.

There is a growing number of evidence-based indications for pharmacogenetic (PGx) testing. We aimed to evaluate clinical relevance of a 16-gene panel test for PGx-guided pharmacotherapy. In an observational cohort study, we included subjects tested with a PGx panel for variants of ABCB1, COMT, CYP1A2, CYP2B6, CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, CYP4F2, DPYD, OPRM1, POR, SLCO1B1, TPMT and VKORC1. PGx-guided pharmacotherapy management was supported by the PGx expert system SONOGEN XP. The primary study outcome was PGx-based changes and recommendations regarding current and potential future medication. PGx-testing was triggered by specific drug-gene pairs in 102 subjects, and by screening in 33. Based on PharmGKB expert guidelines we identified at least one "actionable" variant in all 135 (100%) tested patients. Drugs that triggered PGx-testing were clopidogrel in 60, tamoxifen in 15, polypsychopharmacotherapy in 9, opioids in 7, and other in 11 patients. Among those, PGx variants resulted in clinical recommendations to change PGx-triggering drugs in 33 (32.4%), and other current pharmacotherapy in 23 (22.5%). Additional costs of panel vs. single gene tests are moderate, and the efficiency of PGx panel testing challenges traditional cost-benefit calculations for single drug-gene pairs. However, PGx-guided pharmacotherapy requires specialized expert consultations with interdisciplinary collaborations.

Implementation and management outcomes of pharmacogenetic CYP2C19 testing for clopidogrel therapy in clinical practice.

PURPOSE: The antiplatelet prodrug clopidogrel is bioactivated by the polymorphic enzyme CYP2C19. Prospective clinical studies demonstrated an association between CYP2C19 loss of function (LoF) variants and an increased risk of thrombotic events under clopidogrel, but pharmacogenetic (PGx) testing is not frequently implemented in clinical practice. We report our experience with PGx-guided clopidogrel therapy with particular regard to clinically relevant patient management changes. METHODS: We conducted an observational study analyzing patients that underwent PGx testing for clopidogrel therapy at two Swiss hospitals. Primary outcome was the proportion of patients with clinically relevant PGx-based management recommendations and their implementation. The association of recurrent ischemic events under clopidogrel with CYP2C19 LoF variants and other factors was explored in a multivariate case-control analysis. RESULTS: Among 56 patients undergoing PGx testing, 18 (32.1%) were classified as CYP2C19 intermediate or poor metabolizers. This resulted in 17 recommendations for a change of antiplatelet therapy, which were implemented in 12 patients (70.1%). In the remaining five patients, specific reasons for non-implementation could be identified. Recurrent ischemic events under clopidogrel were associated with LoF variants (OR 2.2, 95% CI 0.3-14.4) and several cardiovascular risk factors. Associations were not statistically significant in our small study, but plausible and in line with estimates from large prospective studies. CONCLUSION: PGx-guided clopidogrel therapy can identify patients with an elevated risk of ischemic events and offer evidence-based alternative treatments. Successful implementation in clinical practice requires a personalized interdisciplinary service that evaluates indications and additional risk factors, provides specific recommendations, and proactively follows their implementation.

EFSUMB 2020 Proposal for a Contrast-Enhanced Ultrasound-Adapted Bosniak Cyst Categorization - Position Statement.

The well-established Bosniak renal cyst classification is based on contrast-enhanced computed tomography determining the malignant potential of cystic renal lesions. Ultrasound has not been incorporated into this pathway. However, the development of ultrasound contrast agents coupled with the superior resolution of ultrasound makes it possible to redefine the imaging of cystic renal lesions. In this position statement, an EFSUMB Expert Task Force reviews, analyzes, and describes the accumulated knowledge and limitations and presents the current position on the use of ultrasound contrast agents in the evaluation of cystic renal lesions.

[CME Sonography 91: Differential Diagnosis of Lower Abdominal Pain]. / CME-Sonografie 91: Differenzialdiagnose von Unterbauchschmerzen CME-Fragen.

CME Sonography 91: Differential Diagnosis of Lower Abdominal Pain Abstract. Pain in the lower abdomen is a frequent reason for further imaging clarification by sonography. The most frequent causes are appendicitis and diverticulitis, in addition to ureteral stones, ovarian and tubal pathology as well as various hernias. Appendicitis has a characteristic clinical presentation and can be diagnosed by CT or ultrasound. In children, the differential diagnosis is that of mesenteric lymphadenitis. Diverticulitis, often right-sided, can also be reliably diagnosed with CT or ultrasound. Not to be forgotten is the left-sided diverticulitis, which occurs more frequently in Asian persons. Appendicitis epiploica should be recognized to avoid unnecessary operations. The iliopsoas syndrome, which is diagnosed by sonopalpation, often remains undetected.

Comparing Blended Learning with Faculty-Led Ultrasound Training: Protocol for a Randomised Controlled Trial (The SIGNATURE Trial).

Background: Ultrasound is increasingly used in clinical practice as a bedside tool. As medical graduates first encounter the technique in early residency, ultrasound training needs to be integrated into the undergraduate curriculum. In Switzerland, abdominal ultrasound skills have been taught by a faculty-led, 21-hour course. However, this course does not have sufficient capacity to meet the increasing demand, and there have been doubts about its effectiveness as a teaching method. We therefore developed a 21-hour blended-learning course, comprising five hours of e-learning and 16 hours of near-peer tutoring. This study investigates whether this new teaching format is as good as, or superior to, the faculty-led method. Methods: The SIGNATURE study is an investigator-initiated, two-arm, randomised controlled trial, enrolling 152 medical students at the Universities of Bern, Fribourg and Zurich. Stratified by study site, students are 1:1 randomised to either the blended-learning course or the faculty-led 2.5-day ultrasound course. Students undergo a six-station objective structured clinical examination (OSCE) and complete an online questionnaire immediately after the course and 6 months later. Discussion: If demonstrated to be effective, the blended-learning course would allow an increase in the number of undergraduate medical students that can acquire ultrasound skills before starting their residencies.

[Introduction of an Ultrasound Course Based on Peer-Tutoring - An Update on the Blended Learning Basic Course Sonography]. / Einführung eines «Peer Tutoring¼ -basierten, Ultraschallkurses ­ ein Update zum «Blended-Learning¼-Basiskurs Sonografie.

Introduction of an Ultrasound Course Based on Peer-Tutoring - An Update on the Blended Learning Basic Course Sonography Abstract. Following the introduction of the new Swiss learning objectives catalogue 'PROFILES', the ability to carry out simple ultrasound examinations has become mandatory for undergraduates. Thanks to a collaboration between the Bern Institute of Primary Health Care and the 'Young Sonographers' SGUM section, the SGUM's classic-format basic abdomen teaching module has been changed into a 'blended learning' teaching format with 'peer tutoring'. It is particularly intended for students and junior doctors. Since the beginning of 2019, local 'Young Sonographers' subsections have gradually introduced the basic ultrasound course for students at four different Swiss universities. This article describes the implementation of the 'Blended Learning Basic Sonography Course' in Switzerland and the current student peer tutor activity at Swiss universities. We discuss the project's successes and current challenges, the Young Sonographers section, and look into the future of ultrasound training in Switzerland.

[Renal Monomorphology in COVID-19 with Acute Renal Insufficiency]. / Nierensonomorphologie bei COVID-19 mit akuter Niereninsuffizienz.

Renal Monomorphology in COVID-19 with Acute Renal Insufficiency Abstract. A 78-year-old ventilator-dependent COVID-19 patient developed severe renal failure with an estimated glomerular filtration rate of 20 ml/min per 1.73 m2 and nephrotic proteinuria. Sonography showed echo-dense and enlarged kidneys with high resistance indices (>0.8). Echocontrast sonography showed a delayed renal perfusion. In the further course of the disease renal function recovered, kidney size decreased and the renal perfusion normalized. An acute COVID-19-associated interstitial nephritis is postulated.

Medical Student Ultrasound Education, a WFUMB Position Paper, Part II. A consensus statement of ultrasound societies.

Ultrasound is becoming a fundamental first-line diagnostic tool for most medical specialties and an innovative tool to teach anatomy, physiology and pathophysiology to undergraduate and graduate students. However, availability of structured training programs during medical school is lagging behind and many physicians still acquire all their ultrasound skills during postgraduate training.There is wide variation in medical student ultrasound education worldwide. Sharing successful educational strategies from early adopter medical schools and learning from leading education programs should advance the integration of ultrasound into the university medical school curricula. In this overview, we present current approaches and suggestions by ultrasound societies concerning medical student educa-tion throughout the world. Based on these examples, we formulate a consensus statement with suggestions on how to integrate ultrasound teaching into the preclinical and clinical medical curricula.

[CME Sonography 89: Differential Diagnosis of Kidney Masses]. / CME-Sonografie 89: Differenzialdiagnose von Nierenraumforderungen.

CME Sonography 89: Differential Diagnosis of Kidney Masses Abstract. Cystic and solid renal lesions are common in ultrasound diagnostics. The solid pseudotumor of the kidney, the so-called renal parenchymal cone, is found in up to 50 % of patients. Pathologically-anatomically it is either a hypertrophy of the column of Bertini or the entire renal lobus, which is located in the renal sinus. Renal cysts were found in a dissected section in 50 % of those over 50 years old. The cystic lesions are subdivided into five categories with the Bosniak classification. This classification is possible with CECT, CEMR and CEUS. The solid lesions are also evaluated by these methods, but the distinction is more difficult here. By measuring the echo intensity in ultrasound, the differentiation of the hyperechoic angiomyolipomas from other solid tumors and pseudotumors is possible. In color-coded Doppler sonography (CCDS), the clear-cell renal cell carcinoma (RCC) is often depicted with many tumor vessels, the remaining tumors with few or only single vessels. In CEUS and TIC, this tumor is shown to be highly perfused, and the influx in the TIC is often faster and stronger than in the surrounding healthy renal cortex. The other tumors are mostly perfused to a lesser extent, especially the papillary carcinomas are significantly less perfused than the renal cortex.

[Ultrasound Course in Ifakara (Tanzania) with Case Studies]. / Ultraschallkurs in Ifakara (Tansania) mit Fallbeispielen.

Ultrasound Course in Ifakara (Tanzania) with Case Studies Abstract. Presentation of two practical cases from the ultrasound course in Ifakara, Tanzania. Case 1 shows the diagnostic value of abdominal and thorax ultrasound in a polytraumatized patient with splenic rupture. In case 2 the sonographic signs of pulmonary and extrapulmonary tuberculosis are presented.