Jan Jesper Andreasen

Human galanin: Primary structure and indentification of two molecular forms

From acid/ethanol extracts of surgical specimens of human large intestine we isolated two peptides, in approximately equal amounts, that reacted with an antiserum against porcine galanin. By amino acid analysis, sequence analysis and mass spectrometry, the larger of the two peptides was found to consist of 30 amino acid residues, the sequence of which was identical to that of porcine galanin except for the following substitutions: Val16, Asn17, Asn36, Thr20 and Scr30. Unlike porcine galanin, the caboxy‐terminus was not amidated. The smaller peptide corresponded to the first 19 amino acid residues counted from the N‐terminus of the 30 residue peptide (again without amidation). The structural analysis was repeated on another batch of tissue with identical results. By HPLC analysis of extracts of specimens from a further 4 patients, the same peptides were identified. Thus, human galanin includes two peptides of 19 and 30 amino acids that share the sequence of the N‐terminal 15 residues with other mammalian galanins, but exhibit characteristic differences in the remaining part of the molecules.

Transfusion of blood during cardiac surgery is associated with higher long-term mortality in low-risk patients

OBJECTIVE Numerous reports have emphasized the need for reduction in transfusions of allogeneic red blood cells (RBC) due to increased morbidity and mortality. Nevertheless, transfusion rates are still high in several cardiac surgery institutions. Reports on long-term survival after cardiac surgery and RBC transfusion are few. METHODS Data from the Western Denmark Heart Registry (WDHR) were used to identify all (25,117) adult cardiac surgery performed in four centres during 1999-2010. Patients with multiple entries (1049), re-do cardiac surgery (985), special/complex procedures (2329), dying within 30 days (668) and not eligible for follow-up (85) were excluded leaving a cohort of 20,001. Registration in the WDHR is mandatory. WDHR and the unique Danish Civil Registration System with continuous sequential updates of the Danish population ensure that all patients and outcomes are accounted for. RESULTS Kaplan-Meier survival plot for low-risk patients (EuroSCORE 0-4), undergoing simple cardiac surgery showed a significantly lower estimated survival after >4500 days (0.637 vs. 0.745) when receiving perioperative RBC transfusion (P<0.0001). The difference was less evident in patients with EuroSCORE 5-9 (0.373 vs. 0.4436, P<0.0001), while high-risk patients showed no difference. Adjusted risk ratio, after RBC transfusion, containing among others age, sex, EuroSCORE and diabetes, was 1.83 (95% CI (confidence interval) 1.67-2.01). The survival rate was independent of up till six units of RBC. CONCLUSION Long-term follow-up of low-risk patients undergoing simple cardiac surgery demonstrates a more than 10% higher mortality when receiving perioperative RBC transfusion. Even transfusion of 1-2 units seems to carry a risk of that magnitude.

Secretion of glucagon-like peptide-1 and reactive hypoglycemia after partial gastrectomy

Glucagon-like peptide-1 is a peptide hormone from the distal small intestine which stimulates insulin secretion and inhibits glucagon secretion and thereby lowers blood glucose. This hormone, therefore, could be involved in the pathogenesis of postprandial reactive hypoglycemia. We subjected 8 patients showing symptoms of early dumping after partial gastrectomy to an oral 100 g glucose load and measured blood glucose and plasma insulin, C-peptide, glucagon, enteroglucagon and GLP-1 concentrations for 3.5 h after ingestion. Ten matched controls were treated similarly. The patients had higher blood glucose concentrations for the initial 60 min, but lower values for the remaining test period with a nadir of 2.76 +/- 0.19 mmol/l at 146 +/- 17 min after glucose (controls: 3.36 +/- 0.21 mmol/l at 210 +/- 9 min). GLP-1 and enteroglucagon responses were grossly elevated in patients compared to controls and insulin and C-peptide levels were higher during the initial 60 min. Glucagon concentrations increased in patients and decreased in controls. When hypoglycemia occurred, GLP-1 levels were only moderately elevated and insulin and C-peptide levels were lower and glucagon levels higher in patients than in controls. Thus, mechanisms other than release of GLP-1 seem to be responsible for the observed changes in the concentrations of glucose and glucoregulatory hormones.

Storage time of allogeneic red blood cells is associated with risk of severe postoperative infection after coronary artery bypass grafting

OBJECTIVE The storage time of allogeneic red blood cells (RBCs) has been linked with the risk of severe postoperative infections following cardiac surgery. However, existing data are sparse and inconsistent. We therefore examined the association between the age of transfused RBCs and development of severe postoperative infection following coronary artery bypass grafting (CABG) in a large population-based cohort study. METHODS The study included patients undergoing CABG with or without concomitant cardiac surgery between June 2003 and July 2008 in the North and Central Denmark regions. Data on demography, perioperative variables, allogeneic blood transfusion and severe postoperative infections (deep sternal wound infection, bacteremia or septicemia) were retrieved from medical databases and medical records. We used logistic regression analyses to compute the crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for the association between storage time of transfused RBCs and the risk of severe infection. RESULTS A total of 4240 patients were included in the final analyses, and 1748 of these patients (41%) were transfused with RBCs. Among transfused patients, 953 were exclusively transfused with RBC stored for < 14 days and 548 were exclusively transfused with RBC stored for ≥ 14 days. Severe infection was identified in 165 patients (3.9%). The adjusted ORs for severe infection among all transfused patients and patients transfused with RBCs stored exclusively for either < 14 days or ≥ 14 days were 1.6 (95% CI: 0.9-2.8), 1.1 (95% CI: 0.6-2.1), and 2.3 (95% CI: 1.2-4.2), respectively, when compared with non-transfused patients. There was a dose-response relationship between the number of transfused RBC units and the risk of severe infection among patients exclusively transfused with RBCs stored for ≥ 14 days. CONCLUSION Although the risk of possible confounding could not be eliminated entirely in this observational study, the findings add further support for the hypothesis that storage time of RBCs is positively associated with the risk of transfusion-related severe postoperative infection in patients undergoing CABG.

Effect of selective serotonin reuptake inhibitors on requirement for allogeneic red blood cell transfusion following coronary artery bypass surgery

BackgroundSelective serotonin reuptake inhibitors (SSRIs) inhibit platelet function, and use of these drugs has been associated with bleeding events. The objective of this study was to examine whether the requirement for red blood cell transfusion was increased following preoperative use of SSRIs among patients undergoing coronary artery bypass grafting (CABG).MethodsA population-based cohort study of transfusion requirements (red blood cells, fresh frozen plasma, and/or platelets) was conducted among patients undergoing CABG at either Aalborg or Skejby Hospitals between 1 January 1998 and 31 December 2003. All prescriptions for antidepressants, including SSRIs, filled before the date of admission for CABG were identified using prescription databases. Patients were categorized according to use of antidepressants (never users, current users [<90 days before admission for CABG], and former users). Antidepressants were classified according to their action on serotonin and norepinephrine reuptake mechanisms. Relative risk (RR) for transfusion were adjusted for: age; sex; preoperative use of platelet inhibitors (low-dose aspirin [acetylsalicylic acid], clopidogrel, and dipyridamole), NSAIDs and oral anticoagulants; place of surgery; extracorporeal circulation; concomitant valve surgery; and Charlson comorbidity index score.ResultsThere were 124 (3.5%) current users of SSRIs among 3454 patients. Adjusted RRs for transfusion among current users of SSRIs, users of nonselective serotonin reuptake inhibitor antidepressants, and users of other antidepressants were 1.1 (95% CI 0.9, 1.3), 0.9 (95% CI 0.6, 1.3), and 1.0 (95% CI 0.7, 1.5), respectively, when compared with never users of any type of antidepressant. The adjusted RR among former SSRI users was 1.0 (95% CI 0.7, 1.4). Risk of re-exploration for bleeding and mortality within 30 days did not differ according to the examined drug-exposure categories.ConclusionPreoperative use of SSRIs was not associated with any substantially increased requirement for allogeneic red blood cell transfusion among patients undergoing CABG. The main strengths of this study are its relatively large size, the use of prospectively collected data obtained from population-based databases with complete follow-up, and the ability to examine specific types of antidepressants. The limitations include a lack of detailed clinical data regarding other factors that may influence transfusion requirements.

Failure to detect Chlamydia pneumoniae in calcific and degenerative arteriosclerotic aortic valves excised during open heart surgery.

Chlamydia pneumoniae has been associated with atherosclerosis, although no causal association has been established. Employing culture and polymerase chain reaction in aortic valves with calcific and degenerative arteriosclerotic changes from 23 non‐consecutive patients undergoing aortic valve replacement, C. pneumoniae was not detected in any of the valves. 19/22 patients had serological evidence of past infection with C. pneumoniae. Our findings do not provide supportive evidence for the hypothesis that C. pneumoniae is associated with calcific or degenerative arteriosclerotic aortic heart valve disease.

Acute Kidney Injury and Long-term Risk of Cardiovascular Events After Cardiac Surgery: A Population-Based Cohort Study

OBJECTIVE To examine the impact of postoperative acute kidney injury (AKI) on the long-term risk of myocardial infarction, heart failure, stroke, and all-cause mortality after elective cardiac surgery. The authors investigated whether time of onset of AKI altered the association between AKI and the adverse events. DESIGN Population-based cohort study in 2006-2011. SETTING Two university hospitals. PARTICIPANTS Adult elective cardiac surgical patients. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS AKI was defined as an increase in baseline creatinine according to the Kidney Disease Improving Global Outcomes criteria. AKI was defined within 30 days of surgery, and also analyzed as early- or late-onset AKI. The authors followed patients from postoperative day 30 until hospitalization with myocardial infarction, heart failure, stroke, or death. Adjustment for confounding factors was done using propensity scores and standardized-mortality-ratio weights. A total of 1,457 (30.7%) of 4,742 patients developed AKI within 30 days of surgery and 470 (9.9%) patients experienced a composite cardiovascular endpoint. Comparing patients with and without postoperative AKI, weighted hazard ratio (HR) and 95% confidence intervals (CI) of 5-year risk of the composite cardiovascular endpoint was 1.41 (95% CI: 1.11-1.80). For each endpoint separately the weighted HR was similarly increased. Ninety-one days to 5-year weighted HR of all-cause mortality was 1.37 (95% CI: 1.05-1.80). The effect of AKI was similar for early- and late-onset AKI. CONCLUSIONS Early- and late-onset AKI within 30 days of elective cardiac surgery was associated with a similarly increased 5-year risk of myocardial infarction, heart failure, stroke, and increased all-cause mortality.

Precautions related to midline sternotomy in cardiac surgery A review of mechanical stress factors leading to sternal complications

Background: After midline sternotomy patients are instructed on activity precautions to avoid sternal wound complications. We questioned how restrictive these precautions must be, since they can lead to a postoperative decrease in quality of life. Aims: To identify mechanical stress factors causing sternal instability and infection in order to create evidence based guidelines for activity following sternotomy. Methods: Literature review. Results: No evidence was found to support weight limitation regarding activity, as long as the upper arms are kept close to the body and activity is within a pain-free range. Recommendations: Avoid stretching both arms backwards at the same time (10 days); loaded activities should be done with the elbows close to the body (eight weeks); only move arms within a pain-free range; use leg rolling with counterweighing when getting in and out of bed; when coughing cross the arms in a “self-hugging” posture; supportive bra or vest is recommended when breast cup ≥ D, body mass index ≥ 35 or frequent cough. Conclusion: This study provides insights into mechanical stress factors acting upon sternum and the overlying skin. Recommendations on activity precautions based on these finding have a patient supportive approach focusing on possibilities and not restrictions.

The release of gastric inhibitory peptide, glucagon-like peptide-I, and insulin after oral glucose test in colectomized subjects

BACKGROUND The physiologic role of the colon as an endocrine organ is not clear. We therefore studied the enteroinsular axis in patients with ulcerative colitis after colectomy. METHODS The subjects included 11 patients with a conventional ileostomy, 10 patients with an ileoanal reservoir, and 10 normal controls. The concentrations of glucose, insulin, gastric inhibitory peptide (GIP), and glucagon-like peptide-I (GLP-I) were measured in plasma during an oral glucose test. RESULTS The peak level of glucose and peak levels and area under the curve (AUC) of insulin and GIP were higher in patients (P < 0.05). Neither the peak level nor the AUC of GLP-I differed between patients and controls, but time to peak level was four times longer in patients with an ileoanal reservoir (P < 0.05). CONCLUSION Colectomy seems to affect the enteroinsular axis, leading to hyperinsulinemia and an impaired glucose tolerance. Moreover, patients with an ileoanal reservoir have a slower GLP-I response after intake of glucose.

Cardiac Patients’ Walking Activity Determined by a Step Counter in Cardiac Telerehabilitation: Data From the Intervention Arm of a Randomized Controlled Trial

Background Walking represents a large part of daily physical activity. It reduces both overall and cardiovascular diseases and mortality and is suitable for cardiac patients. A step counter measures walking activity and might be a motivational tool to increase and maintain physical activity. There is a lack of knowledge about both cardiac patients’ adherence to step counter use in a cardiac telerehabilitation program and how many steps cardiac patients walk up to 1 year after a cardiac event. Objective The purpose of this substudy was to explore cardiac patients’ walking activity. The walking activity was analyzed in relation to duration of pedometer use to determine correlations between walking activity, demographics, and medical and rehabilitation data. Methods A total of 64 patients from a randomized controlled telerehabilitation trial (Teledi@log) from Aalborg University Hospital and Hjoerring Hospital, Denmark, from December 2012 to March 2014 were included in this study. Inclusion criteria were patients hospitalized with acute coronary syndrome, heart failure, and coronary artery bypass grafting or valve surgery. In Teledi@log, the patients received telerehabilitation technology and selected one of three telerehabilitation settings: a call center, a community health care center, or a hospital. Monitoring of steps continued for 12 months and a step counter (Fitbit Zip) was used to monitor daily steps. Results Cardiac patients walked a mean 5899 (SD 3274) steps per day, increasing from mean 5191 (SD 3198) steps per day in the first week to mean 7890 (SD 2629) steps per day after 1 year. Adherence to step counter use lasted for a mean 160 (SD 100) days. The patients who walked significantly more were younger (P=.01) and continued to use the pedometer for a longer period (P=.04). Furthermore, less physically active patients weighed more. There were no significant differences in mean steps per day for patients in the three rehabilitation settings or in the disease groups. Conclusions This study indicates that cardiac telerehabilitation at a call center can support walking activity just as effectively as telerehabilitation at either a hospital or a health care center. In this study, the patients tended to walk fewer steps per day than cardiac patients in comparable studies, but our study may represent a more realistic picture of walking activity due to the continuation of step counter use. Qualitative studies on patients’ behavior and motivation regarding step counter use are needed to shed light on adherence to and motivation to use step counters. Trial Registration ClinicalTrails.gov NCT01752192; https://clinicaltrials.gov/ct2/show/NCT01752192 (Archived by WebCite at http://www.webcitation.org/6fgigfUyV)