Rising serum sodium levels are associated with a concurrent development of metabolic alkalosis in critically ill patients

PURPOSE Changes in electrolyte homeostasis are important causes of acid-base disorders. While the effects of chloride are well studied, only little is known of the potential contributions of sodium to metabolic acid-base state. Thus, we investigated the effects of intensive care unit (ICU)-acquired hypernatremia on acid-base state. METHODS We included critically ill patients who developed hypernatremia, defined as a serum sodium concentration exceeding 149 mmol/L, after ICU admission in this retrospective study. Data on electrolyte and acid-base state in all included patients were gathered in order to analyze the effects of hypernatremia on metabolic acid-base state by use of the physical-chemical approach. RESULTS A total of 51 patients were included in the study. The time of rising serum sodium and hypernatremia was accompanied by metabolic alkalosis. A transient increase in total base excess (standard base excess from 0.1 to 5.5 mmol/L) paralleled by a transient increase in the base excess due to sodium (base excess sodium from 0.7 to 4.1 mmol/L) could be observed. The other determinants of metabolic acid-base state remained stable. The increase in base excess was accompanied by a slight increase in overall pH (from 7.392 to 7.429, standard base excess from 0.1 to 5.5 mmol/L). CONCLUSIONS Hypernatremia is accompanied by metabolic alkalosis and an increase in pH. Given the high prevalence of hypernatremia, especially in critically ill patients, hypernatremic alkalosis should be part of the differential diagnosis of metabolic acid-base disorders.

Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial

IMPORTANCE International guidelines advocate a 7- to 14-day course of systemic glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease (COPD). However, the optimal dose and duration are unknown. OBJECTIVE To investigate whether a short-term (5 days) systemic glucocorticoid treatment in patients with COPD exacerbation is noninferior to conventional (14 days) treatment in clinical outcome and whether it decreases the exposure to steroids. DESIGN, SETTING, AND PATIENTS REDUCE: (Reduction in the Use of Corticosteroids in Exacerbated COPD), a randomized, noninferiority multicenter trial in 5 Swiss teaching hospitals, enrolling 314 patients presenting to the emergency department with acute COPD exacerbation, past or present smokers (≥20 pack-years) without a history of asthma, from March 2006 through February 2011. INTERVENTIONS Treatment with 40 mg of prednisone daily for either 5 or 14 days in a placebo-controlled, double-blind fashion. The predefined noninferiority criterion was an absolute increase in exacerbations of at most 15%, translating to a critical hazard ratio of 1.515 for a reference event rate of 50%. MAIN OUTCOME AND MEASURE Time to next exacerbation within 180 days. RESULTS Of 314 randomized patients, 289 (92%) of whom were admitted to the hospital, 311 were included in the intention-to-treat analysis and 296 in the per-protocol analysis. Hazard ratios for the short-term vs conventional treatment group were 0.95 (90% CI, 0.70 to 1.29; P = .006 for noninferiority) in the intention-to-treat analysis and 0.93 (90% CI, 0.68 to 1.26; P = .005 for noninferiority) in the per-protocol analysis, meeting our noninferiority criterion. In the short-term group, 56 patients (35.9%) reached the primary end point; 57 (36.8%) in the conventional group. Estimates of reexacerbation rates within 180 days were 37.2% (95% CI, 29.5% to 44.9%) in the short-term; 38.4% (95% CI, 30.6% to 46.3%) in the conventional, with a difference of -1.2% (95% CI, -12.2% to 9.8%) between the short-term and the conventional. Among patients with a reexacerbation, the median time to event was 43.5 days (interquartile range [IQR], 13 to 118) in the short-term and 29 days (IQR, 16 to 85) in the conventional. There was no difference between groups in time to death, the combined end point of exacerbation, death, or both and recovery of lung function. In the conventional group, mean cumulative prednisone dose was significantly higher (793 mg [95% CI, 710 to 876 mg] vs 379 mg [95% CI, 311 to 446 mg], P < .001), but treatment-associated adverse reactions, including hyperglycemia and hypertension, did not occur more frequently. CONCLUSIONS AND RELEVANCE In patients presenting to the emergency department with acute exacerbations of COPD, 5-day treatment with systemic glucocorticoids was noninferior to 14-day treatment with regard to reexacerbation within 6 months of follow-up but significantly reduced glucocorticoid exposure. These findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN19646069.

Identification of a SIRT1 mutation in a family with type 1 diabetes.

Type 1 diabetes is caused by autoimmune-mediated β cell destruction leading to insulin deficiency. The histone deacetylase SIRT1 plays an essential role in modulating several age-related diseases. Here we describe a family carrying a mutation in the SIRT1 gene, in which all five affected members developed an autoimmune disorder: four developed type 1 diabetes, and one developed ulcerative colitis. Initially, a 26-year-old man was diagnosed with the typical features of type 1 diabetes, including lean body mass, autoantibodies, T cell reactivity to β cell antigens, and a rapid dependence on insulin. Direct and exome sequencing identified the presence of a T-to-C exchange in exon 1 of SIRT1, corresponding to a leucine-to-proline mutation at residue 107. Expression of SIRT1-L107P in insulin-producing cells resulted in overproduction of nitric oxide, cytokines, and chemokines. These observations identify a role for SIRT1 in human autoimmunity and unveil a monogenic form of type 1 diabetes.

Differential uptake of (68)Ga-DOTATOC and (68)Ga-DOTATATE in PET/CT of gastroenteropancreatic neuroendocrine tumors

PURPOSE Abundant expression of somatostatin receptors (sst) is a characteristic of neuroendocrine tumors (NET). Thus, radiolabeled somatostatin analogs have emerged as important tools for both in vivo diagnosis and therapy of NET. The two compounds most often used in functional imaging with positron emission tomography (PET) are (68)Ga-DOTATATE and (68)Ga-DOTATOC. Both analogs share a quite similar sst binding profile. However, the in vitro affinity of (68)Ga-DOTATATE in binding the sst subtype 2 (sst2) is approximately tenfold higher than that of (68)Ga-DOTATOC. This difference may affect their efficiency in detection of NET lesions, as sst2 is the predominant receptor subtype on gastroenteropancreatic NET. We thus compared the diagnostic value of PET/CT with both radiolabeled somatostatin analogs ((68)Ga-DOTATATE and (68)Ga-DOTATOC) in the same patients with gastroenteropancreatic NET. PATIENTS AND METHODS Twenty-seven patients with metastatic gastroenteropancreatic NET underwent (68)Ga-DOTATOC and (68)Ga-DOTATATE PET/CT as part of the workup before prospective peptide receptor radionuclide therapy (PRRT). The performance of both imaging methods was analyzed and compared for detection of individual lesions per patient and for eight defined body regions. A region was regarded as positive if at least one lesion was detected in that region. In addition, radiopeptide uptake in terms of the maximal standardized uptake value (SUV(max)) was compared for concordant lesions and renal parenchyma. RESULTS Fifty-one regions were found positive with both (68)Ga-DOTATATE and (68)Ga-DOTATOC. Overall, however, significantly fewer lesions were detected with (68)Ga-DOTATATE in comparison with (68)Ga-DOTATOC (174 versus 179, p < 0.05). Mean (68)Ga-DOTATATE SUV(max) across all lesions was significantly lower compared with (68)Ga-DOTATOC (16.9 ± 6.8 versus 22.1 ± 12.0, p < 0.01). Mean SUV(max) for renal parenchyma was not significantly different between (68)Ga-DOTATATE and (68)Ga-DOTATOC (12.6 ± 2.6 versus 12.6 ± 2.7). CONCLUSIONS (68)Ga-DOTATOC and (68)Ga-DOTATATE possess similar diagnostic accuracy for detection of gastroenteropancreatic NET lesions (with a potential advantage of (68)Ga-DOTATOC) despite their evident difference in affinity for sst2. Quite unexpectedly, maximal uptake of (68)Ga-DOTATOC tended to be higher than its (68)Ga-DOTATATE counterpart. However, tumor uptake shows high inter- and intraindividual variance with unpredictable preference of one radiopeptide. Thus, our data encourage the application of different sst ligands to enable personalized imaging and therapy of gastroenteropancreatic NET with optimal targeting of tumor receptors.

CT dose and image quality in the last three scanner generations.

AIM To compare the computed tomography (CT) dose and image quality with the filtered back projection against the iterative reconstruction and CT with a minimal electronic noise detector. METHODS A lung phantom (Chest Phantom N1 by Kyoto Kagaku) was scanned with 3 different CT scanners: the Somatom Sensation, the Definition Flash and the Definition Edge (all from Siemens, Erlangen, Germany). The scan parameters were identical to the Siemens presetting for THORAX ROUTINE (scan length 35 cm and FOV 33 cm). Nine different exposition levels were examined (reference mAs/peek voltage): 100/120, 100/100, 100/80, 50/120, 50/100, 50/80, 25/120, 25/100 and 25 mAs/80 kVp. Images from the SOMATOM Sensation were reconstructed using classic filtered back projection. Iterative reconstruction (SAFIRE, level 3) was performed for the two other scanners. A Stellar detector was used with the Somatom Definition Edge. The CT doses were represented by the dose length products (DLPs) (mGycm) provided by the scanners. Signal, contrast, noise and subjective image quality were recorded by two different radiologists with 10 and 3 years of experience in chest CT radiology. To determine the average dose reduction between two scanners, the integral of the dose difference was calculated from the lowest to the highest noise level. RESULTS When using iterative reconstruction (IR) instead of filtered back projection (FBP), the average dose reduction was 30%, 52% and 80% for bone, soft tissue and air, respectively, for the same image quality (P < 0.0001). The recently introduced Stellar detector (Sd) lowered the radiation dose by an additional 27%, 54% and 70% for bone, soft tissue and air, respectively (P < 0.0001). The benefit of dose reduction was larger at lower dose levels. With the same radiation dose, an average of 34% (22%-37%) and 25% (13%-46%) more contrast to noise was achieved by changing from FBP to IR and from IR to Sd, respectively. For the same contrast to noise level, an average of 59% (46%-71%) and 51% (38%-68%) dose reduction was produced for IR and Sd, respectively. For the same subjective image quality, the dose could be reduced by 25% (2%-42%) and 44% (33%-54%) using IR and Sd, respectively. CONCLUSION This study showed an average dose reduction between 27% and 70% for the new Stellar detector, which is equivalent to using IR instead of FBP.

Electrocardiographic ST-segment monitoring during controlled occlusion of coronary arteries

Background: Ischemia monitoring cannot always be performed by 12-lead ECG. Hence, the individual performance of the ECG leads is crucial. No experimental data on the ECG's specificity for transient ischemia exist. Methods: In 45 patients a 19-lead ECG was registered during a 1-minute balloon occlusion of a coronary artery (left anterior descending artery [LAD], right coronary artery [RCA] or left circumflex artery [LCX]). ST-segment shifts and sensitivity/specificity of the leads were measured. Results: During LAD occlusion, V3 showed maximal ST-segment elevation (0.26 mV [IQR 0.16–0.33 mV], p = 0.001) and sensitivity/specificity (88% and 80%). During RCA occlusion, III showed maximal ST-elevation (0.2 mV [IQR 0.09–0.26 mV], p = 0.004), aVF had the best sensitivity/specificity (85% and 68%). During LCX occlusion, V6 showed maximal ST-segment elevation (0.04 mV [IQR 0.02–0.14 mV], p = 0.005), and sensitivity/specificity was (31%/92%) but could be improved (63%/72%) using an optimized cut-off for ischemia. Conclusion: V3, aVF and V6 show the best performance to detect transient ischemia.

Tastend von Gott reden : drei systematisch-theologische Antrittsvorlesungen aus Bern

Nach Gott tasten ist die Grundbewegung, die die drei in diesem Band versammelten Vorlesungen verknüpft und für die Paul Klees «Engel, noch tastend» zum hermeneutischen Leitbild wird. Torsten Meireis, inspiriert durch Karl Barth, reflektiert inmitten religiöser und weltanschaulicher Pluralität ein moralisches Verhalten, das dem Handeln des in Jesus Christus offenbaren Gottes entspricht. Wegweisend wird ihm dabei ein dreifacher Begriff des Guten: unverfügbares, intendiertes und realisiertes Gutes. Um angesichts des Sinnverlustes religiöser Rede dennoch nicht von Gott zu schweigen, plädiert Andreas Krebs, angeregt durch Ludwig Wittgensteins Spätphilosophie, für ein «halbes Sagen, halbes Verstehen», das sich in der Nähe zur Sprache der Poesie weiss – eine Gottesrede, die sich ihrer selbst nicht mehr sicher ist und gerade so Gott Gewicht zu geben sucht. Als Baustein einer um den Eigennamen kreisenden Eschatologie entwirft Magdalene L. Frettlöh die Hoffnung auf eine als neuschöpferischen göttlichen Namensruf an die Toten verstandene Auferweckung. Diese schliesst Rettung wie Verwandlung des irdischen Lebens ein.