Basophil activation test with progressively less heated forms of egg distinguishes egg allergic from tolerant children.

BACKGROUND AND OBJECTIVE: Diagnosis of egg allergy through basophil activation testing (BAT) has been mainly performed with an egg white extract or individual egg allergens rather than clinically more representative whole-egg extracts. Impact of heating on whole-egg extract allergenicity remains unassessed.Validating BAT with gradually less heated whole-egg extracts in egg allergy diagnosis and as tolerance marker. METHODS: CD63-based BAT was performed with five progressively less heated extracts from cake, hard-boiled egg, omelet, soft-boiled, and raw egg in 10 egg allergic (EA), 10 complete egg tolerant (ET) and 12 non-egg-sensitized non-allergic (NEA) children. Cutoffs and diagnostic accuracy measures were established through ROC analysis. Changes in basophil response were assessed in 12 baked egg tolerant children undergoing an 8-month gradual egg reintroduction protocol with BAT and oral food challenges prior to each reintroduction step. RESULTS: Basophil responses to all egg extracts were increased in EA, but not in ET and NEA children. Responses decreased progressively with more heated egg extracts. Compared to ET children, EA children showed higher basophil sensitivity for all egg extracts. Negative BAT responses predicted clinical tolerance with a 90-100% sensitivity, 100% specificity, and false positive rate of 2.78%. In comparison, egg sIgE's (<0.35 kUA/L) had a lower specificity of 50-78% with a false positive rate of 40%. Basophil reactivity and sensitivity tended to decrease in baked egg tolerant children undergoing gradual egg reintroduction, concurrent with tolerance development. CONCLUSION: BAT with progressively less heated egg preparations is a sensitive and highly specific tool to discriminate EA from ET children.

Surgical Myocardial Revascularization with a Composite T-graft from the Left Internal Mammary Artery-Comparison of the Great Saphenous Vein with the Radial Artery.

BACKGROUND: Composite T-grafts between left internal mammary artery (LIMA) and radial artery (RA) are a common concept in complete arterial myocardial revascularization. The aim of the present study was to investigate whether the use of the great saphenous vein (SV) instead of RA leads to comparably good results in terms of outcome in this context. METHODS: Patients who underwent myocardial revascularization with a T-graft using RA or a segment of SV to the right coronary artery or circumflex artery between the beginning of 2014 and the end of 2019 at the Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel were included. To minimize surgical variation, only patients were observed by a single senior surgeon in the department. Exclusion criteria were previous cardiac surgery, preoperative extracorporeal circulatory support, off-pump surgery, additional aortocoronary bypasses, and cardiac combination procedures. RESULTS: A total of 115 patients were studied. In 55 patients, the T-graft was placed between the LIMA and SV, and in 60 patients, the T-graft was placed between the LIMA and RA. Patients in the SV group were older (70.6 ± 7.8 vs. 58.5 ± 10.0 years; p < 0.001), suffered more frequently from non-ST elevation myocardial infarction (12.7 vs. 1.7%; p = 0.027), arterial hypertension (83.6 vs. 61.7%; p = 0.009), and atrial fibrillation (18.2 vs. 1.7%; p = 0.003). They were less likely to be active smokers (16.4 vs. 38.3%; p = 0.009) and less likely to have a history of variceal surgery (0 vs. 15.0%; p = 0.003). Calcification of the ascending aorta was also found more frequently in the saphenous group (18.2 vs. 3.3%, p = 0.009). Operative times and number of distal anastomoses did not differ significantly between the two groups. Postoperative deliriums (16.7 vs. 5.0%; p = 0.043) were observed more frequently in venous patients. Wound healing disorders of the leg (11.1 vs. 0%; p = 0.011) did only occur in SV group and wound infections of the arm only in the RA group. Complete follow-up was achieved in 74.8% of cases. Median follow-up was 60.3 (39.6; 73.2) months. Serious adverse cardiac-cerebral events (19.0 vs. 22.7%; p = 0.675) and mortality (14.5 vs. 6.7%; p = 0.167) did not differ significantly between the groups at follow-up. Myocardial infarction (0 vs. 2.5%; p = 1.000) and stroke (0 vs. 7.5%; p = 0.245) were observed exclusively in RA group. Percutaneous coronary intervention was required in single patients of RA group (0 vs. 15.0%; p = 0.028). No patient from either group underwent repeat coronary artery bypass grafting (CABG). The patients of SV group had angiographically competent grafts and open anastomoses. Graft failure was noted in a single patient in RA group, in which case both grafts and native coronary vessels were stented. Kaplan-Meier analysis revealed no significant survival disadvantage for SV group compared with RA group. CONCLUSION: CABG with a composite T-graft between LIMA and a segment of SV may be comparable to bypass surgery with a composite T-graft between LIMA and RA. This might be true in terms of morbidity and mortality over an intermediate-term observation period. The results of our studies give rise to the hypothesis that the decision not to perform aortic bypass anastomosis may be more important than the choice of graft material.

Health-related quality of life, emotional burden, and neurocognitive function in the first generation of metastatic melanoma survivors treated with pembrolizumab: a longitudinal pilot study.

PURPOSE: The aim of this study was to assess the evolution of health-related quality of Life (HRQoL), emotional burden, and neurocognitive function in the first-generation metastatic melanoma survivors treated with pembrolizumab. METHODS: Survivors were defined as patients who achieved a durable remission for at least 6 months after initiating pembrolizumab in a single-center observational study (N = 141). A semi-structured interview was performed at baseline. Neurocognitive computerized testing and patient-reported outcomes were collected at 4 time points to assess HRQoL using the EORTC QLQ-C30 and the HADS to assess anxiety and depression. RESULTS: Out of 35 eligible patients, 25 were recruited and completed baseline assessment (18 female; median age 58 years [range 28-86]; 24 completed the 1-year follow-up phase. Median time since diagnosis was 30 months (range 12-84); median time since initiation of pembrolizumab was 19 months (range 6-42). At all visits, survivors reported a significantly lower global HRQoL, lower physical, emotional, cognitive, role, and social functioning compared with the European Mean of the healthy population. Fifteen patients (64%) had clinical levels of anxiety/depression at one time point during follow-up. The clinical interview revealed that 12 patients (48%) suffered from Cancer-Related-Post-Traumatic-Stress disorder, of whom 7 (28%) developed transient suicidal ideation, 1 patient made a suicide attempt. Neurocognitive testing revealed cognitive impairment in 8 patients (32%). CONCLUSIONS: Metastatic melanoma survivors, treated successfully with pembrolizumab, are at risk for suffering from emotional distress and neurocognitive impairment with a persistent impact on their HRQOL. Timely detection in order to offer tailored care is indicated.

Disease burden of congenital cytomegalovirus infection at school entry age: study design, participation rate and birth prevalence.

Congenital cytomegalovirus infection (cCMV) may lead to symptoms at birth and long-term consequences. We present a nationwide, retrospective cohort study on the outcome of cCMV up to age 6 years. For this study we identified cCMV, using polymerase chain reaction, by analysing dried blood spots, which are taken shortly after birth for neonatal screening. The group of children with cCMV were compared to a group of children who were cCMV negative at birth. Data were collected about their health and development up to age 6 years. Parents of 73 693 children were invited to participate, and 32 486 (44·1%) gave informed consent for testing of their child's dried blood spot for CMV. Of the 31 484 dried blood spots tested, 156 (0·5%) were positive for cCMV. Of these, four (2·6%) children had been diagnosed with cCMV prior to this study. This unique retrospective nationwide study permits the estimation of long-term sequelae of cCMV up to the age of 6 years. The birth prevalence of cCMV in this study was 0·5%, which is in line with prior estimates. Most (97·4%) children with cCMV had not been diagnosed earlier, indicating under-diagnosis of cCMV.

The German Aortic Valve Registry (GARY): in-hospital outcome.

BACKGROUND: Aortic stenosis is a frequent valvular disease especially in elderly patients. Catheter-based valve implantation has emerged as a valuable treatment approach for these patients being either at very high risk for conventional surgery or even deemed inoperable. The German Aortic Valve Registry (GARY) provides data on conventional and catheter-based aortic procedures on an all-comers basis. METHODS AND RESULTS: A total of 13 860 consecutive patients undergoing repair for aortic valve disease [conventional surgery and transvascular (TV) or transapical (TA) catheter-based techniques] have been enrolled in this registry during 2011 and baseline, procedural, and outcome data have been acquired. The registry summarizes the results of 6523 conventional aortic valve replacements without (AVR) and 3464 with concomitant coronary bypass surgery (AVR + CABG) as well as 2695 TV AVI and 1181 TA interventions (TA AVI). Patients undergoing catheter-based techniques were significantly older and had higher risk profiles. The stroke rate was low in all groups with 1.3% (AVR), 1.9% (AVR + CABG), 1.7% (TV AVI), and 2.3% (TA AVI). The in-hospital mortality was 2.1% (AVR) and 4.5% (AVR + CABG) for patients undergoing conventional surgery, and 5.1% (TV AVI) and AVI 7.7% (TA AVI). CONCLUSION: The in-hospital outcome results of this registry show that conventional surgery yields excellent results in all risk groups and that catheter-based aortic valve replacements is an alternative to conventional surgery in high risk and elderly patients.

Cardiac surgery in Germany during 2013: a report on behalf of the German Society for Thoracic and Cardiovascular Surgery.

On the basis of a voluntary registry of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS), data of all cardiac surgical procedures performed in 79 German cardiac surgical units during the year 2013 are presented. In 2013, a total of 99,128 cardiac surgical procedures (implantable cardioverter defibrillator [ICD] and pacemaker procedures excluded) were submitted to the registry. More than 13.8% of the patients were older than 80 years, which remains equal in comparison to the previous year. In-hospital mortality in 40,410 isolated coronary artery bypass grafting procedures (84.5% on-pump and 15.5% off-pump) was 2.9%. In 29,672 isolated valve procedures (including 7,722 catheter-based procedures), an in-hospital mortality of 4.7% was observed. This long-lasting registry of the GSTCVS will continue to be an important tool for quality control and voluntary public reporting by illustrating current facts and developments of cardiac surgery in Germany.

[Basic standards for a department of cardiac surgery. Quality requirements for the care of cardiac patients in connection with operations on the heart, the heart vessels and thoracic organ transplantation]. / Basisstandards einer Fachabteilung für Herzchirurgie. Qualitätsanforderungen für die Versorgung von herzkranken Patientinnen und Patienten im Zusammenhang mit Operationen/Eingriffen am Herzen, den herznahen Gefäßen und der thorakalen Organtransplantation.

Current evolutions and substantial amendments of the German health care system in combination with distinguished progress in cardiac surgery over the past years require both a reflection of principles in patient-centered care and an update of basic standard requirements for a department of cardiac surgery in Germany. In due consideration of the data from the voluntary registry of the German Society for Thoracic and Cardiovascular Surgery, this article accurately defines core requirements for a cardiac surgical department (cardiac surgery on-site), subdivided into facilities, staff and processes. If based on these standards, one may anticipate that cardiac surgical care is performed under appropriate conditions leading to an intrinsic benefit for patients.

Unprotected left main coronary artery disease. Surgical therapy.

Coronary artery bypass grafting (CABG) has been established as a safe concept in the treatment of unprotected left main coronary artery (ULMCA) disease and is considered the first-line treatment in current interdisciplinary guidelines. Regardless of the complexity of the lesion and the concomitant diseases, CABG is associated with excellent long-term results. Randomized controlled trials investigating the role of percutaneous coronary intervention in the setting of ULMCA lesions are frequently underpowered and suggest that, when restricted to less complex lesions, percutaneous coronary intervention is associated with results comparable to surgery. Thus, there is an urgent need for further randomized controlled trials RCTs with all-comers design to supply precise data under real-life conditions representative of the left main stem anatomy. Until then, an interdisciplinary approach to patients with ULMCA lesions is mandatory in view of the existing guidelines.

Comparison of the hepatitis B virus core, surface and polymerase gene substitution rates in chronically infected patients.

For phylogenetic comparison of hepatitis B virus (HBV) isolates, often a region of the HBV surface gene is analysed. Because the surface gene completely overlaps the polymerase gene, its evolution is constrained, and it may not be the best choice for genetic comparison of HBV isolates. Analysing serial sample pairs of 33 chronically HBV-infected, untreated patients, with a cumulative follow-up of 184 years, the synonymous and nonsynonymous substitution rates of a part of the overlapping HBV surface and polymerase genes were compared to those of a nonoverlapping part of the HBV core gene. The substitution rate of the HBV core gene was higher (8.15 × 10(-4) vs 4.57 × 10(-4) substitutions/site/year) than that of the surface gene. The difference was mainly due to a significantly lower synonymous substitution rate in the surface gene, with dN/dS ratios of 0.412 in the core gene and 0.986 in the surface gene. Contrary to the core gene, the number of substitutions in the surface gene was higher in low viraemic hosts, who control HBV infection by suppressing replication. The number of substitutions in the core gene correlated more strongly with the duration of follow-up. The overlapping HBV surface and polymerase genes experience strong negative selection, which limits the number of substitutions. Because the HBV core gene reflects the duration of infection more accurately, it is more suitable for the analysis of short-term viral evolution and of hepatitis B transmission chains.

aepEX monitor for the measurement of hypnotic depth in patients undergoing balanced xenon anaesthesia.

BACKGROUND: Previously, we showed a significant difference in the measurements of hypnotic depth by the bispectral index (BIS) and auditory-evoked potentials (AEPs) using the A-line autoregressive index during xenon anaesthesia. In the present study, we evaluate the alternative AEP-based auditory-evoked potential index (aepEX) for the measurement of hypnotic depth in patients undergoing general anaesthesia with xenon. METHODS: Forty-two patients undergoing elective abdominal surgery were enrolled in this controlled, double-blinded, randomized, clinical study. Patients were randomized to receive either xenon (n=21) or sevoflurane anaesthesia (n=21). During anaesthesia, BIS values were recorded simultaneously with the aepEX monitoring. The anaesthetist performing the anaesthesia was blinded to the hypnotic depth monitors. After surgery, the incidence of recalls and awareness was evaluated. RESULTS: Patients' characteristics such as gender, age, and weight did not differ between the groups. The aepEX and BIS values behaved similarly during anaesthesia. The comparison of aepEX values during xenon and sevoflurane anaesthesia revealed significantly lower aepEX values in the xenon group after 25 min [xenon: 32.9 (4.8) vs sevoflurane: 39.3 (9.0); P=0.008] and after 35 min [xenon: 31.4 (6.6) vs sevoflurane: 37.0 (6.8); P=0.012]. During anaesthesia, aepEX values correlated with the clinical evaluation of depth of anaesthesia (e.g. >20% changes of the baseline arterial pressure or heart rate, spontaneous breathing and/or intolerance of mechanical ventilation, coughing, abdominal pressing, sweating, eye tearing). CONCLUSIONS: We found the aepEX monitor to provide index in the range of adequate depth of xenon anaesthesia, when combined with remifentanil infusion in intubated patients undergoing elective abdominal surgery.

The German Aortic Valve Registry (GARY): a nationwide registry for patients undergoing invasive therapy for severe aortic valve stenosis.

Background The increasing prevalence of severe aortic valve defects correlates with the increase of life expectancy. For decades, surgical aortic valve replacement (AVR), under the use of extracorporeal circulation, has been the gold standard for treatment of severe aortic valve diseases. In Germany ~12,000 patients receive isolated aortic valve surgery per year. For some time, percutaneous balloon valvuloplasty has been used as a palliative therapeutic option for very few patients. Currently, alternatives for the established surgical procedures such as transcatheter aortic valve implantation (TAVI) have become available, but there are only limited data from randomized studies or low-volume registries concerning long-time outcome. In Germany, the implementation of this new technology into hospital care increased rapidly in the past few years. Therefore, the German Aortic Valve Registry (GARY) was founded in July 2010 including all available therapeutic options and providing data from a large quantity of patients.Methods The GARY is assembled as a complete survey for all invasive therapies in patients with relevant aortic valve diseases. It evaluates the new therapeutic options and compares them to surgical AVR. The model for data acquisition is based on three data sources: source I, the mandatory German database for external performance measurement; source II, a specific registry dataset; and source III, a follow-up data sheet (generated by phone interview). Various procedures will be compared concerning observed complications, mortality, and quality of life up to 5 years after the initial procedure. Furthermore, the registry will enable a compilation of evidence-based indication criteria and, in addition, also a comparison of all approved operative procedures, such as Ross or David procedures, and the use of different mechanical or biological aortic valve prostheses.Results Since the launch of data acquisition in July 2010, almost all institutions performing aortic valve procedures in Germany joined the registry. By now, 91 sites which perform TAVI in Germany participate and more than 15,000 datasets are already in the registry.Conclusion The implementation of new or innovative medical therapies needs supervision under the conditions of a well-structured scientific project. Up to now relevant data for implementation of TAVI and long-term results are missing. In contrast to randomized controlled trials, GARY is a prospective, controlled, 5-year observational multicenter registry, and a real world investigation with only one exclusion criterion, the absence of patients' written consent.

Impact of the Eurotransplant high-urgency heart allocation system on the outcome of transplant candidates in Germany.

BACKGROUND: In 2000, the Eurotransplant Foundation changed the allocation criteria following the enactment of the German Transplantation Law (GTL). Our study investigated the impact of the new allocation system on outcomes after heart transplantation (HTx) in Germany. METHODS: We compared 2 cohorts of patients who underwent HTx at our institution in two different 3-year periods before (Group 1: 01/1995-12/1997) and after (Group 2: 01/2003-12/2005) implementation of the new system. RESULTS: An increase in the ratio of HTx performed on an urgency basis was found in Group 2 (8.3 % vs. 87.2 %; P < 0.001). The median waiting time and the ischemia time were significantly lower in Group 1 ( P < 0.05). Postoperatively, the length of ICU stay was significantly higher in Group 2 ( P = 0.04). CONCLUSION: The new allocation system decreased the proportion of local and regional organ harvesting. It generates a higher ischemia time without increasing the number of transplantations and without improving the clinical outcome after HTx. The severity of heart failure, rate of secondary organ impairment, and comorbidity is markedly elevated in patients waiting for HTx on HU.

[Modern coronary surgery, the SYNTAX trial and updated guidelines]. / Moderne Koronarchirurgie in Zusammenhang mit der SYNTAX-Studie und aktuellen Leitlinien.

Coronary artery bypass grafting (CABG), a modern and safe procedure, is considered the therapy of choice in the care of patients with multi-vessel disease. The 3-year results of the SYNTAX trial not only showed surgical advantages in terms of repeat revascularisation, but the results also demonstrated significant surgical benefit for myocardial infarction and survival rates. More differentiated analyses showed distinct disadvantages in percutaneous coronary intervention (PCI) associated with the greater complexity of coronary pathology. PCI tends to be a comparable therapeutic option only in certain cases of left main stem lesions or multi-vessel disease. The findings from the SYNTAX study herald a new era in the treatment of coronary heart disease in which, as recommended in the updated guidelines issued by the EACTS/ESC in 2010, the interventionalist and the surgeon, working closely together as a"heart team", provide a sound therapy plan for affected patients.

Mumps epidemic in orthodox religious low-vaccination communities in the Netherlands and Canada, 2007 to 2009.

We assessed the epidemiological characteristics of a mumps virus epidemic (genotype D) that occurred in the Netherlands between August 2007 and May 2009 and its association with a subsequent mumps outbreak in Canada. In the Netherlands, five data sources were used: notifications (only mandatory since the end of 2008) (56 cases), laboratory confirmation data (177 cases), a sentinel general practitioner (GP) database (275 cases), hospitalisation data (29 cases) and weekly virological reports (96 cases). The median age of cases in the notification, laboratory and GP databases ranged from 13 to 15 years. The proportion of cases that were unvaccinated ranged from 65% to 85% in the notification, laboratory and GP databases. Having orthodox Protestant beliefs was the main reason for not being vaccinated. In Canada, a mumps virus strain indistinguishable from the Dutch epidemic strain was detected between February and October 2008 in an orthodox Protestant community with historical and family links to the affected community in the Netherlands, suggesting that spread to Canada had occurred. Prevention and control of vaccine-preventable diseases among population subgroups with low vaccination coverage remains a priority.

Persistent and transient hepatitis B virus (HBV) infections in children born to HBV-infected mothers despite active and passive vaccination.

Combined passive and active immunization for newborns very effectively prevents perinatal hepatitis B virus (HBV) infections. In the Netherlands, babies born to hepatitis B surface antigen (HBsAg)-positive women receive passive immunization with hepatitis B and at least three active HBsAg vaccinations. Serological testing for the presence of HBV markers was offered for all infants born to HBsAg-positive mothers between January 2003 and July 2007, after completion of their vaccination schedule. About 75% of the infants (n = 1743) completed their HB-vaccination schedule and participated in the serologic evaluation. Twelve of them (0.7%) were found to be HBV infected. Furthermore, we identified three older children with high levels of anti-HBc, anti-HBs and anti-HBe, while they were HBsAg and HBV DNA negative. This serologic profile is evidence for a resolved HBV infection. In the group of older children (1.5-5 years of age, n = 728), about half of the HBV-infected children (3 of 7) had already cleared their infection at the time of sampling. For a proper evaluation of the efficacy of a new intervention programme to prevent vertical HBV transmission, it is also important to analyse the HBV markers in serum collected when the children are older than 1.5 years. In a programmatic setting, all children born to HBV-infected mothers should be tested not only for the level of anti-HBs but also for the absence of HBsAg, because 2 of the 12 HBV-infected children (17%) had a high level of anti-HBs.

Octogenarians undergoing combined aortic valve replacement and myocardial revascularization: perioperative mortality and medium-term survival.

OBJECTIVE: Aim of the study was to answer the question whether the mortality and morbidity of octogenarians undergoing combined aortic valve replacement and myocardial revascularization (AVR + CABG) is higher than that of younger patients. PATIENTS AND METHODS: Between 01/1995 and 12/2002, 242 patients underwent AVR + CABG in our institution. 37 patients were older than 80 years (16 male, 21 female, median pressure gradient over the aortic valve: 53 mmHg, median EF: 62%), 205 patients were younger than 80 years (133 male, 72 female, median gradient 48 mmHg, median EF: 61%). NYHA class, aortic valve area and valve calcification were worse in the 80+ group. Biological valve prostheses were implanted in 94.6% of the older and in 45.4% of the younger patients (p < 0.001). RESULTS: Perioperative complications occurred more often (p = 0.0188) in the 80+ group (86.5% experienced 1 or more complications) than in the 80- group (66.3%). Similarly, the MACE (Major Adverse Cardiovascular Events) rate was higher (p = 0.0448) in the 80+ group than in the 80- group. Bleeding occurred (p = 0.092) more often in younger (9.3%) than in older (0%) patients, while renal insufficiency was more frequent (p = 0.0164) in older (21.6%) than in younger patients (7.8 %). The 30-day mortality was higher (p = 0.0045) in older (21.6%) than in younger patients (5.8%). Multivariate analysis revealed an odds ratio for early death of 2.9 (CI 1.014-8.397) for patients older than 80 years. The late death rate within the first 5 years after surgery was comparable in both groups (80- group 24.4%, 80+ group 24.3%). Postoperative quality of life was significantly worse in the 80+ group in 4 out of 8 functions. CONCLUSIONS: Octogenarians undergoing AVR + CABG have a relatively high perioperative complication rate and mortality, but show a stable medium-term survival. The perioperative complication rate is higher in older than in younger patients, and the postoperative quality of life with regard to bodily functions is acceptable but significantly worse than that of younger patients.

Cooperation in Microbial Populations: Theory and Experimental Model Systems.

Cooperative behavior, the costly provision of benefits to others, is common across all domains of life. This review article discusses cooperative behavior in the microbial world, mediated by the exchange of extracellular products called public goods. We focus on model species for which the production of a public good and the related growth disadvantage for the producing cells are well described. To unveil the biological and ecological factors promoting the emergence and stability of cooperative traits we take an interdisciplinary perspective and review insights gained from both mathematical models and well-controlled experimental model systems. Ecologically, we include crucial aspects of the microbial life cycle into our analysis and particularly consider population structures where ensembles of local communities (subpopulations) continuously emerge, grow, and disappear again. Biologically, we explicitly consider the synthesis and regulation of public good production. The discussion of the theoretical approaches includes general evolutionary concepts, population dynamics, and evolutionary game theory. As a specific but generic biological example, we consider populations of Pseudomonas putida and its regulation and use of pyoverdines, iron scavenging molecules, as public goods. The review closes with an overview on cooperation in spatially extended systems and also provides a critical assessment of the insights gained from the experimental and theoretical studies discussed. Current challenges and important new research opportunities are discussed, including the biochemical regulation of public goods, more realistic ecological scenarios resembling native environments, cell-to-cell signaling, and multispecies communities.

C2 therapeutic drug monitoring of cyclosporine is a safe and feasible method in de novo heart transplant patients.

BACKGROUND: The narrow therapeutic window of cyclosporine (CsA) requires close therapeutic drug monitoring (TDM). While C2-TDM has been established after renal and liver transplantations, clinical experience is limited for patients after de novo heart transplantation (HTX). PATIENTS AND METHODS: In a retrospective study, we investigated 40 patients undergoing HTX; 34 patients received induction therapy using antithymocyte globulin (ATG Mérieux). Immunosuppression was administered with CsA (Sandimmun-Optoral), with dosages adjusted according to C2 levels (800-1100 ng/mL during the first 6 months and reduced to 400-600 ng/mL from the beginning of the first year). At different times TI (months 1-3). TII (months 12-14) TIII (months 24-26), and TIV (months 34-36), we obtained measures of acute cellular rejections (ARs), cytomegalovirus (CMV) infections, creatinine, and safety laboratory parameters. RESULTS: The cumulative survival was 95% after 1 year, and 88% after 3.8 years. Eight ARs were diagnosed at a mean of 7.6 months after HTX in 7 patients. Twenty-four CMV infections/reactivations were verified. In 10 cases, treatment was started because of clinical symptoms. The mean creatinine values significantly rose in the early postoperative phase (TI: 1.23+/-0.47 mg/dL, TII: 1.49+/-0.41 mg/dL; P<.0001). Thereafter the creatinine values declined; however, this was not statistically significant (TIII: 1.38+/-0.57 mg/dL, TIV: 1.15+/-0.30 mg/dL). All other safety parameters showed no significant changes. CONCLUSIONS: C2 allows individualization of immunosuppression with reduced CsA toxicity, but without loss in safety among de novo patients after HTX. We obtained freedom from severe AR, a low number of CMV infections, and excellent patient survival.

Serum anticholinergic activity in patients following cardiac surgery and healthy individuals following amitriptyline application.

The serum anticholinergic activity (SAA) is used as a marker for cognitive impairment. Here, two studies have been performed characterizing the SAA profile. In Study 1 the endogenous SAA in relation to the total serum protein concentration was monitored for 24 h in five healthy individuals and compared with that in four inpatients following cardiac surgery. In Study 2 the SAA of seven healthy individuals was assessed following a single amitriptyline dose. In both studies SAA was assessed by an ex vivo assay. In Study 1, the absolute SAA varied in a wide range of 1.2 and 14.5 atropine equivalents (AEs) over 24 h. A circadian pattern was not observed. The mean total serum protein concentration, but not the SAA, was significantly lower in inpatients than in healthy individuals. In Study 2, the SAA increased following amitriptyline to a maximum. The mean SAA increased by 6.39 AE at the amitriptyline peak concentration. High SAA variability showed a low statistical relation to amitriptyline concentrations. Both studies characterize the SAA as an individual parameter not affected per se by surgery or clinical care and poorly correlated with the total serum protein concentration. The relation with amitriptyline concentration helps to quantify SAA values towards a better understanding of the clinical implications and limitations of SAA changes.