[Perioperative fluid management in major abdominal surgery]. / Perioperatives Flüssigkeitsmanagement bei großen viszeralchirurgischen Eingriffen.

Intravascular fluid administration belongs to the cornerstones of perioperative treatment with a substantial impact on surgical outcome especially with respect to major abdominal surgery. By avoidance of hypovolemia and hypervolemia, adequate perioperative fluid management significantly contributes to the reduction of insufficient tissue perfusion as a determinant of postoperative morbidity and mortality. The effective use of intravascular fluids requires detailed knowledge of the substances as well as measures to guide fluid therapy. Fluid management already starts preoperatively and should be continued in the postoperative setting (recovery room, peripheral ward) considering a patient-adjusted and surgery-adjusted hemodynamic monitoring. Communication between all team members participating in perioperative care is essential to optimize fluid management.

Implementation of the Sepsis-3 definition in German university intensive care units : A survey.

BACKGROUND: The old definition of sepsis was replaced by Sepsis-3 in February 2016. The new screening diagnostic tools sequential organ failure assessment (SOFA) score and quick SOFA (qSOFA) score were incorporated into the definition. The resulting scientific controversy led to several retrospective and prospective evaluations. In contrast no evaluation of the state of play of national implementation of Sepsis-3 has been conducted so far. OBJECTIVE: The aim of this study was to capture the current situation in German academic intensive care units 1 year after the implementation of Sepsis-3. METHODS: An internet-based questionnaire consisting of 22 items was developed. The identification of eligible departments was performed by an online search of the homepages of all university hospitals located in Germany. Departments regardless of the discipline with an explicit indication of involvement in intensive care were extracted. The link to the internet-based questionnaire was sent to all identified departments on 22 February 2017 and was accessible for 19 days. RESULTS: Out of 259 departments 76 answered the online survey. The response rate was 29.3% from 13 specializations. Anesthesiology, internal medicine and general surgery were the three main participants in this study. The majority of intensive care units (54.75%) treated more than 100 patients with sepsis or septic shock annually and more than 30% treated more than 250 patients. While 76.7% of respondents had a standard operating procedure, 55% of those were based on the Sepsis-3 definition. When asked to rate the usefulness of the Sepsis-3 definition, answers were heterogeneous with a slight tendency towards a higher usefulness and the majority (72.9%) were in favor of Sepsis-3 being included in the national S2K guidelines. CONCLUSION: The results demonstrate the heterogeneity of Sepsis-3 implementation in German intensive care units. Sepsis-3 is finding its way but there is a need for standardized implementation.

The impact of real life treatment strategies for Candida peritonitis-A retrospective analysis.

Candida species are commonly detected isolates from abdominal foci. The question remains as to who would benefit from early empiric treatment in cases of Candida peritonitis. This study collected real-life data on critically ill patients with Candida peritonitis to estimate the relevance of the chosen treatment strategy on the outcome of these patients. One hundred and thirty-seven surgical intensive care unit (ICU) patients with intra-abdominal invasive Candidiasis were included in the study. Fifty-six patients did not get any antifungal agent. Twenty-nine patients were empirically treated, and 52 patients were specifically treated. In the group without, with empiric and with specific antifungal treatment, the 30-day mortality rate was 33.9, 48.3 and 44.2 respectively. Candida albicans was the most frequently found species. Seven patients in the specific treatment group and one patient in the empiric treatment group emerged with candidaemia. Age, leucocyte count, APACHE II Score and acute liver failure were independent predictors of 30-day mortality in patients with Candida peritonitis. Not all patients with Candida peritonitis received antifungal treatment in real clinical practice. Patients with higher morbidity more often got antifungals. Early empirical therapy has not been associated with a better 30-day mortality.

Sepsis-induced long-term immune paralysis--results of a descriptive, explorative study.

BACKGROUND: Long-lasting impairment of the immune system is believed to be the underlying reason for delayed deaths after surviving sepsis. We tested the hypothesis of persisting changes to the immune system in survivors of sepsis for the first time. METHODS: In our prospective, cross-sectional pilot study, eight former patients who survived catecholamine-dependent sepsis and eight control individuals matched for age, sex, diabetes and renal insufficiency were enrolled. Each participant completed a questionnaire concerning morbidities, medications and infection history. Peripheral blood was collected for determination of i) immune cell subsets (CD4(+), CD8(+) T cells; CD25(+) CD127(-) regulatory T cells; CD14(+) monocytes), ii) cell surface receptor expression (PD-1, BTLA, TLR2, TLR4, TLR5, Dectin-1, PD-1 L), iii) HLA-DR expression, and iv) cytokine secretion (IL-6, IL10, TNF-α, IFN-γ) of whole blood stimulated with either α-CD3/28, LPS or zymosan. RESULTS: After surviving sepsis, former patients presented with increased numbers of clinical apparent infections, including those typically associated with an impaired immune system. Standard inflammatory markers indicated a low-level inflammatory situation in former sepsis patients. CD8(+) cell surface receptor as well as monocytic HLA-DR density measurements showed no major differences between the groups, while CD4(+) T cells tended towards two opposed mechanisms of negative immune cell regulation via PD-1 and BTLA. Moreover, the post-sepsis group showed alterations in monocyte surface expression of distinct pattern recognition receptors; most pronouncedly seen in a decrease of TLR5 expression. Cytokine secretion in response to important activators of both the innate (LPS, zymosan) and the adaptive immune system (α-CD3/28) seemed to be weakened in former septic patients. CONCLUSIONS: Cytokine secretion as a reaction to different activators of the immune system seemed to be comprehensively impaired in survivors of sepsis. Among others, this could be based on trends in the downregulation of distinct cell surface receptors. Based on our results, the conduct of larger validation studies seems feasible, aiming to characterize alterations and to find potential therapeutic targets to engage.

In vitro expansion of U87-MG human glioblastoma cells under hypoxic conditions affects glucose metabolism and subsequent in vivo growth.

Hypoxia is a characteristic feature of solid tumors leading to the over expression of hypoxia-inducible factor (HIF)-1α protein and therefore to a specific cellular behavior. However, even though the oxygen tension in tumors is low (<5 %), most of the cell lines used in cancer studies are grown under 21 % oxygen tension. This work focuses on the impact of oxygen conditions during in vitro cell culture on glucose metabolism using 1-(13)C-glucose. Growing U87-MG glioma cells under hypoxic conditions leads to a two- to threefold reduction of labeled glutamine and an accumulation of fructose. However, under both hypoxic and normoxic conditions, glucose is used for de novo synthesis of pyrimidine since the (13)C label is found both in the uracil and ribose moieties. Labeling of the ribose ring demonstrates that U87-MG glioma cells use the reversible branch of the non-oxidative pentose phosphate pathway. Interestingly, stereotactic implantation of U87-MG cells grown under normoxia or mild hypoxia within the striatum of nude mice led to differential growth; the cells grown under hypoxia retaining an imprint of the oxygen adaptation as their development is then slowed down.

[Metformin-induced lactic acidosis : Severe symptoms with difficult diagnostics]. / Metformininduzierte Laktatacidose : Schweres Krankheitsbild mit schwieriger Diagnosestellung.

Metformin-induced lactic acidosis is a rare but severe disease for the individual patients. A case of a 64-year-old patient with diabetes mellitus type 2 suffering from this disease is presented where metformin accumulation was caused by prerenal acute kidney failure. The clinical evaluation up to the final diagnosis, the pathophysiology and the appropriate therapy are presented in detail. Additionally, the current guidelines regarding the perioperative management of metformin administration are summarized. The case described aims to direct attention to the rare but, nevertheless, severe symptoms of metformin-induced lactic acidosis.

[Epigenetic regulation in sepsis : current state of knowledge]. / Epigenetische Regulation in der Sepsis : Aktueller Wissensstand.

Sepsis is known to be a severe systemic immune reaction based on an infection of various origins. The initial immune response is accompanied by excess activation of immune cells and release of proinflammatory cytokines. Simultaneously initiated compensatory mechanisms lead to high levels of anti-inflammatory mediators to counterbalance the generalized inflammatory reaction; however, the compensatory immunoreaction itself equally overreacts and results in a prolonged sepsis-induced immunosuppression. The underlying mechanisms for these exaggerated immune responses and the resulting global immunosuppression that increase the risk for secondary infection are still unknown. Recent findings indicate that epigenetic mechanisms change basic properties of important immune cells by mechanisms leading to changes in gene expression. Dynamic exchanges of histone modifications result in a variation of transcription and seem to play a key role in cell function of macrophages and other immune cells. This article provides a current overview of epigenetic sepsis research and the sepsis-induced effects on the immune system.

[Use of biomarkers in sepsis. Update and perspectives]. / Einsatz von Biomarkern in der Sepsis. Update und Ausblick.

Sepsis and related complications are a challenge for intensive care medicine. Despite many advances in antibiotic therapy sepsis remains one of the most common diseases of patients in intensive care units and is designated as the main cause of death in critically ill patients. Persisting sepsis leads to impaired immunity, resulting in immunosuppression. Unspecific predictive signs complicate an early diagnosis; however, an early initiation of adequate therapy is of crucial importance for the prognosis. Scoring systems can be applied for the initial evaluation but are controversially discussed concerning the monitoring of disease progression and therapy as well as outcome prediction. Biomarkers are considered as a complementary approach.

The serum growth hormone-binding protein is reduced in young patients with insulin-dependent diabetes mellitus.

Despite elevated serum concentrations of GH, longitudinal growth is stunted in a considerable number of children and adolescents with insulin-dependent diabetes mellitus (IDDM). To elucidate, whether reduced peripheral action of GH contributes to this phenomenon, GH-binding protein (GH-BP) activity was measured in 117 children and adolescents with IDDM (mean age 14.6 yr, range 4.5-28 yr) and 132 healthy controls (13.1 yr, 6.3-26 yr). Serum was incubated with 125I-GH, then chromatographed on a Sephacryl S200 column (1.8.100 cm), apparent binding of 125I-GH to GH-BP was corrected for the amount of endogenous GH present in the sample. GH-BP activity was significantly lower in IDDM patients, with a corrected binding of 16.8 +/- 0.6% compared to 21.3 +/- 0.7% in control children (mean +/- SE; P < 0.0001, Wilcoxon-test). Previous studies demonstrated that GH-BP is increased in healthy overweight children. In contrast, in IDDM children, GH-BP was reduced despite a moderate degree of overweight (z-score for weight: +0.94 +/- 0.12; mean +/- SE). Reduced serum GH-BP activity in IDDM children is further accentuated when compared to healthy children with a similar degree of overweight (22.8 +/- 0.5%; n = 44). Based on this novel finding, we conclude that decreased GH receptor density may explain reduced growth velocity despite increased secretion of GH in some IDDM children.

Binding protein for human growth hormone: effects of age and weight.

In human serum, a specific binding protein with high affinity for human growth hormone (GHBP) is found which is identical to the extracellular portion of the hepatic GH receptor. GHBP is assessed by incubating serum samples with [125I]-GH, followed by separation of bound and free radioactivity using gel chromatography. In newborns and children younger than 2 months, GHBP was practically absent and no 'big-big' GH could be found. GHBP values increased rapidly during the first 2 years of life, followed by a slower increase during childhood and puberty. No difference was found between male and female subjects. Apart from age, standardized weight (SDS = z score) had a major positive effect on GHBP concentration. Interestingly, SDS height correlated negatively with GHBP when weight and age were controlled for. These data may relate to two clinical findings: (1) the developmental switch between GH-independent intrauterine and GH-dependent postnatal growth mechanisms, and (2) the accelerated growth velocity encountered in adipose children.