Resection of the primary tumor was linked to longer survival. Bone marrow toxicity grade 3-4 occurred in 10.8%. One patient (1.0 %) developed acute myeloid leukemia. Bone marrow toxicity was unrelated to type and length of previous chemotherapy, amount of administered activity and absorbed dose to the bone marrow. CONCLUSION 177Lu-DOTATATE therapy was feasible, highly effective and safe in patients with advanced panNETs heavily pretreated with chemotherapy. More than one line of chemotherapy was a therapy related independent risk factor for shorter PFS and OS. © 2020 S. Karger AG, Basel.Hyponatremia is a frequent complication in patients with advanced cirrhosis. Patients with cirrhosis can develop two types of hyponatremia, hypovolemic or hypervolemic (dilutional) hyponatremia. Hypervolemic hyponatremia is the most common type and it develops as a consequence of an impairment in the renal capacity to eliminate solute-free water. The key mechanism leading to solute-free water retention is a non-osmotic hypersecretion of vasopressin (AVP), secondary to a reduction in effective arterial blood pressure existing in patients with advanced cirrhosis. Hypervolemic hyponatremia is associated with increased morbidity and mortality in patients with cirrhosis, and it has also been associated with increased complications after liver transplantation. Currently, the management of hypervolemic hyponatremia in cirrhosis is based on fluid restriction. Vaptans, oral selective vasopressin V2-receptor antagonists, and particularly tolvaptan, have been investigated as a pharmacological approach for the management of hypervolemic hyponatremia in cirrhosis. However, existing information on its efficacy in cirrhosis is still scarce and a recent warning has been raised about their potential role on inducing liver injury at high doses. © 2019 S. Karger AG, Basel.Chronic hyponatremia may not cause overt symptoms, and therefore frequently remains untreated. More recently, growing evidence indicate that this condition is not benign, and can lead to unsteady gait, deterioration of bone mass and strength, increased fragility, and increased all-cause mortality. We provided the first evidence for hyponatremia-induced osteoporosis based on markedly reduced bone mineral density and bone structural changes in hyponatremic rats, which is an experimental model of the syndrome of inappropriate antidiuresis (SIAD). These animal data were supported by results of the analysis of the National Health and Nutrition Examination Survey III dataset showing a 2.5-fold increased OR of osteoporosis in participants with serum sodium concentration [Na+] below 135 mmol/L. A subsequent cross-sectional study from Michigan analyzed data from 25,000 patients and found a strong association between the odds of osteoporosis by bone density and hyponatremia. This study pointed out that age-dependent decline in bone density may mask hyponatremia-induced bone loss. Multiple independent retrospective studies, epidemiological studies, and prospective clinical studies have since confirmed and extended our findings, reporting evidence for increased bone fractures and increased mortality in patients with hyponatremia. Cell culture studies have elucidated some of the adaptive mechanisms by which low extracellular fluid [Na+] increases osteoclast formation and bone resorbing activity, thereby liberating stored sodium from the bone matrix. Studies on older SIAD rats indicated that the damage may not be restricted to bone alone, but may involve other organs, including the heart, testis, kidney, and the brain. Finally, compelling open questions and future research directions about the effect of hyponatremia on bone are outlined. © 2019 S. Karger AG, Basel.Background Carcinoid heart disease (CHD) can develop in patients with carcinoid syndrome (CS), itself caused by overproduction of hormones and other products from some neuroendocrine tumours. The most common hormone is serotonin, detected as high 5-hydroxyindoleacetic acid (5-HIAA). This systematic literature review summarises current literature on the impact of CHD on survival, and the relationship between 5-HIAA levels and CHD development, progression and mortality. Methods MEDLINE, Embase, Cochrane databases and grey literature were searched using terms for CHD, 5-HIAA, disease progression, and mortality/survival. Eligible articles were non-interventional and included patients with CS and predefined CHD and 5-HIAA outcomes. Results Publications reporting on 31 studies were included. The number and disease states of patients varied between studies. Estimates of CHD prevalence and incidence among patients with a diagnosis/symptoms indicative of CS were 3-65% and 3-42%, respectively. Most studies evaluating survival found significantly higher mortality rates among patients with vs without CHD. Patients with CHD reportedly had higher 5-HIAA levels; median urinary levels in patients with vs without CHD were 266-1381 vs 67.5-575 µmol/24 h. Higher 5-HIAA levels were also found to correlate with disease progression (median progression/worsening-associated levels 791-2247 µmol/24 h) and increased odds of death (7% with every 100 nmol/L increase). Conclusions Despite the heterogeneity of studies, the data indicate that CHD reduces survival, and higher 5-HIAA levels are associated with CHD development, disease progression and increased risk of mortality; 5-HIAA levels should be carefully managed in these patients. © 2020 S. Karger AG, Basel.Osteogenic differentiation of human adipose tissue-derived stem cells (hASCs) is a complex process that is regulated by multiple factors, including microRNAs (miRNAs). The miRNA miR-20a was shown to promote bone formation from bone marrow-derived mesenchymal stem cells. However, the role of miR-20a in osteogenic differentiation of hASCs remains unclear. In this study, we systematically evaluated the function of miR-20a in regulating hASC osteogenesis in vitro. hASCs were transduced with miR-20a-overexpressing and miR-20a-sponge lentiviral vectors, with green fluorescent protein (GFP) as a control. The results showed that miR-20a transcription was upregulated after hASC mineralization. Compared with the miR-20a-sponge, GFP, and hASC groups, the miR-20a-overexpressing group showed higher alkaline phosphatase (ALP) activity on days 7 and 14. Moreover, the mRNA level of ALP increased significantly in the miR-20a-overexpressing group on day 14. Furthermore, the protein of the target gene PPARγ was decreased, and the osteogenic differentiation-associated proteins ALP, osteocalcin, and RUNX2 were upregulated. hASCs anchored to HA/β-TCP revealed a healthy polygonal morphology and developed cytoplasmic extensions. miR-20a promoted osteogenic differentiation of the cell scaffold. Taken together, these data -confirm that miRNA-20a promotes the osteogenesis of hASCs in vitro, and its essential role in vivo needs further -investigation. © 2020 S. Karger AG, Basel.BACKGROUND Spontaneous preterm birth is the leading cause of perinatal morbidity and mortality worldwide and continues to present a major clinical dilemma. We previously reported that a number of protein species were dysregulated in maternal serum collected at 11-13+6 weeks’ gestation from pregnancies that continued to labour spontaneously and deliver preterm. OBJECTIVES AND METHODS In this study, we aimed to validate changes seen in 4 candidate protein species alpha-1-antitrypsin, vitamin D-binding protein (VDBP), alpha-1beta-glycoprotein and apolipoprotein A-1 in a larger cohort of women using a western blot approach. RESULTS Serum levels of all 4 proteins were reduced in women who laboured spontaneously and delivered preterm. This reduction was significant for VDBP (p = 0.04), which has been shown to be involved in a plethora of essential biological functions, including actin scavenging, fatty acid transport, macrophage activation and chemotaxis. CONCLUSIONS The decrease in select proteoforms of VDBP may result in an imbalance in the optimal intrauterine environment for the developing foetus as well as to a successful uncomplicated pregnancy. Thus, certain (phosphorylated) species of VDBP may be of value in developing a targeted approach to the early prediction of spontaneous preterm labour. Importantly, this study raises the importance of a focus on proteoforms and the need for any biomarker validation process to most effectively take these into account rather than the more widespread practice of simply focussing on the primary amino acid sequence of a protein. © 2020 S. Karger AG, Basel.Hyponatremia is a frequently encountered clinical finding, and by far the most common disorder of electrolyte and water homeostasis throughout the world. Given the complex pathophysiology of hyponatremia as well as its clinical implications, which range from apparently asymptomatic presentations to life-threatening conditions, a comprehensive understanding of its possible causes and of the frequencies of occurrence of the various types of hyponatremia in distinct clinical settings is essential for successful disease management. In this chapter, the diverse etiologies of hyponatremia are summarized, explained, and classified according to the patients’ extracellular volume status. An in-depth review of the existing literature on epidemiologic data on incidence and prevalence of hyponatremia is provided covering the general population as well as the patient groups with community-acquired and hospital-acquired hyponatremia. Selected clinical scenarios that are described in detail are hyponatremia in the geriatric population, in the emergency department, in the postoperative state, and in the intensive care setting. Distinct diseases and circumstances that are often associated with hyponatremia are reviewed briefly, while a more detailed discussion is covered in later chapters. © 2019 S. Karger AG, Basel.BACKGROUND In patients with suspected stroke, brain imaging is recommended in the acute phase for appropriate management and treatment. Both computed tomography (CT) and magnetic resonance imaging (MRI) are considered reasonable choices for initial brain imaging. When both techniques are available, choosing one or the other might be associated with specific factors related either to patients, stroke symptoms, and severity or management organization. METHODS The study was performed within the STROKE 69 database, a population-based cohort of all adult patients with suspected stroke admitted in one of the emergency departments (ED), primary stroke center, or stroke center of the Rhône County, from November 2015 to December 2016. Patients were included if they were admitted within 24 h following either symptom onset or last known normal. To identify factors potentially associated with the choice of initial brain imaging, a multivariate logistic regression was performed. RESULTS Among the 3,244 patients with suspe choice of first imaging in case of stroke suspicion. These are related to patient characteristics, type of stroke symptoms, and type of organization. © 2020 S. Karger AG, Basel.PURPOSE To investigate the epidemiological status of diabetes mellitus (DM)-related complications in Japan. METHODS The subjects were 3.11 million Japanese individuals who were registered in the Japanese claim database between 2005 and 2014. Subjects with a diagnosis associated with codes related to DM and/or DM-related complications as classified by the International Classification of Diseases version 10 and those who were prescribed any therapeutic agents for DM were considered to have DM. The status of ocular, renal, and neural complications was investigated. RESULTS A total of 66,923 patients with DM were included. The prevalence of subjects with DM was 3.8% in 2005 and 4.2% in 2014. The most frequent complication was diabetic retinopathy (23.6%, 95% CI 21.7%-25.5%), followed by diabetic nephropathy (14.8%, 95% CI 14.0%-15.6%) and diabetic neuropathy (4.9%, 95% CI 4.5%-5.3%). Among the subjects with ocular complications, 1.8% had proliferative diabetic retinopathy, 1.1% had diabetic macular edema (DME), 0.