Islet of Langerhans isolation from pediatric and juvenile donor pancreases

Islet grafts isolated from young donors allow superior functional outcomes but are often associated with poor islet isolation yields. The objective of this study was to comparatively analyze the outcomes of islet isolation between young and older donors. We retrospectively analyzed 564 pancreas isolations performed at our institution. Isolation outcomes were compared between donors aged ≤20 years (n = 42, YD) and >20 years (n = 522, OD). Isolation procedure was identical in both groups. Prepurification percentage of embedded islets was higher in YD (44.3 ± 22.7% vs. 24.9 ± 20.9%, P < 0.001). This led to a lower recovery rate in YD (48% vs. 76%, P = 0.002) and hence lower postpurification IEQ/g pancreas in YD (2 412 ± 1 789 IEQ/g vs. 3 194 ± 1 892 IEQ/g, P = 0.01). Final yield was 180 982 ± 128 073 IEQ in YD and 244 167 ± 134 137 IEQ in OD, (P = 0.006). In vitro function was markedly, albeit nonsignificantly, higher in YD (SI: 4.5 ± 5.1 vs. 3.0 ± 5.7, P = 0.350). Proportion of transplanted preparations was similar in both groups, 38% (16/42) in YD vs. 43% (224/522) in OD, P = 0.628. In spite of isolation and purification difficulties, pancreases from young donors allowed similar islet transplantation rates as older donors. Efforts should be directed at improving islet extraction in these donors to realize their full potential for islet transplantation.     

Poor intraoperative blood glucose control is associated with a worsened hospital outcome after cardiac surgery in diabetic patients

BACKGROUND: Tight perioperative control of blood glucose improves the outcome of diabetic patients undergoing cardiac surgery. Because stress response and cardiopulmonary bypass can induce profound hyperglycemia, intraoperative glycemic control may become difficult. The authors undertook a prospective cohort study to determine whether poor intraoperative glycemic control is associated with increased intrahospital morbidity. METHODS: Two hundred consecutive diabetic patients undergoing on-pump heart surgery were enrolled. A standard insulin protocol based on subcutaneous intermediary insulin was given the morning of the surgery. Intravenous insulin therapy was initiated intraoperatively from blood glucose concentrations of 180 mg/dl or greater and titrated according to a predefined protocol. Poor intraoperative glycemic control was defined as four consecutive blood glucose concentrations greater than 200 mg/dl without any decrease in despite insulin therapy. Postoperative blood glucose concentrations were maintained below 140 mg/dl by using aggressive insulin therapy. The main endpoints were severe cardiovascular, respiratory, infectious, neurologic, and renal in-hospital morbidity. RESULTS: Insulin therapy was required intraoperatively in 36% of patients, and poor intraoperative glycemic control was observed in 18% of patients. Poor intraoperative glycemic control was significantly more frequent in patients with severe postoperative morbidity (37% vs. 10%; P < 0.001). The adjusted odds ratio for severe postoperative morbidity among patients with a poor intraoperative glycemic control as compared with patients without was 7.2 (95% confidence interval, 2.7-19.0). CONCLUSION: Poor intraoperative control of blood glucose concentrations in diabetic patients undergoing cardiac surgery is associated with a worsened hospital outcome after surgery.     

The PROPKD Score: A New Algorithm to Predict Renal Survival in Autosomal Dominant Polycystic Kidney Disease

The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0–3 points), intermediate risk (4–6 points), and high risk (7–9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD.     

Poor Intraoperative Blood Glucose Control Is Associated with a Worsened Hospital Outcome after Cardiac Surgery in Diabetic Patients

Background: Tight perioperative control of blood glucose improves the outcome of diabetic patients undergoing cardiac surgery. Because stress response and cardiopulmonary bypass can induce profound hyperglycemia, intraoperative glycemic control may become difficult. The authors undertook a prospective cohort study to determine whether poor intraoperative glycemic control is associated with increased intrahospital morbidity.

Methods: Two hundred consecutive diabetic patients undergoing on-pump heart surgery were enrolled. A standard insulin protocol based on subcutaneous intermediary insulin was given the morning of the surgery. Intravenous insulin therapy was initiated intraoperatively from blood glucose concentrations of 180 mg/dl or greater and titrated according to a predefined protocol. Poor intraoperative glycemic control was defined as four consecutive blood glucose concentrations greater than 200 mg/dl without any decrease in despite insulin therapy. Postoperative blood glucose concentrations were maintained below 140 mg/dl by using aggressive insulin therapy. The main endpoints were severe cardiovascular, respiratory, infectious, neurologic, and renal in-hospital morbidity.

Results: Insulin therapy was required intraoperatively in 36% of patients, and poor intraoperative glycemic control was observed in 18% of patients. Poor intraoperative glycemic control was significantly more frequent in patients with severe postoperative morbidity (37% vs. 10%; P < 0.001). The adjusted odds ratio for severe postoperative morbidity among patients with a poor intraoperative glycemic control as compared with patients without was 7.2 (95% confidence interval, 2.7-19.0).     

Malaria-Antigene in der Ära der mRNA-Impfstoffe

Monatsschrift Kinderheilkunde - Bereits in den frühen 1990er-Jahren wurde erstmals eine durch einen mRNA-Impfstoff ausgelöste Immunantwort beschrieben. Seitdem wurden mRNA-Impfstoffe...     

What's wrong with fear conditioning?

Fear conditioning is one of the prime paradigms of behavioural neuroscience and a source of tremendous insight in the fundamentals of learning and memory and the psychology and neurobiology of emotion. It is also widely regarded as a model for the pathogenesis of anxiety disorders in a diathesis-stress model of psychopathology. Starting from the apparent paradox between the adaptive nature of fear conditioning and the dysfunctional nature of pathological anxiety, we present a critique of the human fear conditioning paradigm as an experimental model for psychopathology. We discuss the potential benefits of expanding the human fear conditioning paradigm by (1) including action tendencies as an important index of fear and (2) paying more attention to “weak” (i.e., ambiguous) rather than “strong” fear learning situations (Lissek et al., 2006), such as contained in selective learning procedures. We present preliminary data that illustrate these ideas and discuss the importance of response systems divergence in understanding individual differences in vulnerability for the development of pathological anxiety.     

The Hippo pathway: Horizons for innovative treatments of peripheral nerve diseases

Initially identified in Drosophila, the Hippo signaling pathway regulates how cells respond to their environment by controlling proliferation, migration and differentiation. Many recent studies have focused on characterizing Hippo pathway function and regulation in mammalian cells. Here, we present a brief overview of the major components of the Hippo pathway, as well as their regulation and function. We comprehensively review the studies that have contributed to our understanding of the Hippo pathway in the function of the peripheral nervous system and in peripheral nerve diseases. Finally, we discuss innovative approaches that aim to modulate Hippo pathway components in diseases of the peripheral nervous system.     

N-terminal pro-brain natriuretic peptide predicts myocardial ischemia and is related to postischemic left-ventricular dysfunction in patients with stable coronary artery disease.

BACKGROUND: The N-terminal-pro-B natriuretic peptide (Nt-pro-BNP) is of diagnostic and prognostic value in coronary artery disease (CAD). We assessed the relationship between Nt-pro-BNP and (1) the extent of ischemia on stress myocardial perfusion imaging (MPI), and (2) changes between the basal and postexercise ejection fraction (EF), in stable patients with a normal EF. METHODS AND RESULTS: One hundred and two patients with stable, documented CAD (EF, 62% +/- 8%) underwent an exercise-rest thallium-201 gated-MPI and serial Nt-pro-BNP assays. Myocardial perfusion imaging produced abnormal results in 57 patients (56%; group 1), and normal results in 45 patients (44%; group 2). Median baseline, immediate postexercise, and 3-hour postexercise Nt-pro-BNP values were higher in group 1 than in group 2: 182 vs 85, 201 vs 86, and 212 vs 99 pg/mL, respectively (P < .001 for all). Postexercise EF decreased in group 1 (53% +/- 11% vs 62% +/- 10%, P < .001), but not in group 2 (61% +/- 9% vs 62% +/- 7%, NS). The Nt-pro-BNP ruled out significant ischemia with a negative predictive value of 0.90, whereas patients within the higher tertile of Nt-pro-BNP had a fivefold higher risk of ischemia compared with patients within the lower tertile. CONCLUSIONS: The post-stress increase in Nt-pro-BNP is related to myocardial ischemia and to postischemic left-ventricular dysfunction, and accurately predicts the presence or absence of myocardial perfusion defects.