Preoperative portal vein or portal and hepatic vein embolization: DRAGON collaborative group analysis.

BACKGROUND: The extent of liver resection for tumours is limited by the expected functional reserve of the future liver remnant (FRL), so hypertrophy may be induced by portal vein embolization (PVE), taking 6 weeks or longer for growth. This study assessed the hypothesis that simultaneous embolization of portal and hepatic veins (PVE/HVE) accelerates hypertrophy and improves resectability. METHODS: All centres of the international DRAGON trials study collaborative were asked to provide data on patients who had PVE/HVE or PVE on 2016-2019 (more than 5 PVE/HVE procedures was a requirement). Liver volumetry was performed using OsiriX MD software. Multivariable analysis was performed for the endpoints of resectability rate, FLR hypertrophy and major complications using receiver operating characteristic (ROC) statistics, regression, and Kaplan-Meier analysis. RESULTS: In total, 39 patients had undergone PVE/HVE and 160 had PVE alone. The PVE/HVE group had better hypertrophy than the PVE group (59 versus 48 per cent respectively; P = 0.020) and resectability (90 versus 68 per cent; P = 0.007). Major complications (26 versus 34 per cent; P = 0.550) and 90-day mortality (3 versus 16 per cent respectively, P = 0.065) were comparable. Multivariable analysis confirmed that these effects were independent of confounders. CONCLUSION: PVE/HVE achieved better FLR hypertrophy and resectability than PVE in this collaborative experience.

Mouse Models of Nonalcoholic Steatohepatitis: Head-to-Head Comparison of Dietary Models and Impact on Inflammation and Animal Welfare.

A variety of dietary nonalcoholic steatohepatitis (NASH) mouse models are available, and choosing the appropriate mouse model is one of the most important steps in the design of NASH studies. In addition to the histopathological and metabolic findings of NASH, a sufficient mouse model should guarantee a robust clinical status and good animal welfare. Three different NASH diets, a high-fat diet (HFD60), a western diet (WD), and a cafeteria diet (CAFD), were fed for 12 or 16 weeks. Metabolic assessment was conducted at baseline and before scheduled sacrifice, and liver inflammation was analyzed via fluorescence-associated cell sorting and histopathological examination. Clinical health conditions were scored weekly to assess the impact on animal welfare. The HFD60 and WD were identified as suitable NASH mouse models without a significant strain on animal welfare. Furthermore, the progression of inflammation and liver fibrosis was associated with a decreased proportion of CD3+ NK1.1+ cells. The WD represents a model of advanced-stage NASH, and the HFD60 is a strong model of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. However, the CAFD should not be considered a NASH model.

Elastic TPU Mesh as Abdominal Wall Inlay Significantly Reduces Defect Size in a Minipig Model.

Background: The open abdomen with mesh implantation, followed by early reoperation with fascial closure, is a modern surgical approach in difficult clinical situations such as severe abdominal sepsis. As early fascial closure is not possible in many cases, mesh-mediated fascial traction is helpful for conditioning of a minimized ventral hernia after open abdomen. The aim of this study was to evaluate the clinical utilization of an innovative elastic thermoplastic polyurethane mesh (TPU) as an abdominal wall inlay in a minipig model. Methods: Ten minipigs were divided in two groups, either receiving an elastic TPU mesh or a nonelastic polyvinylidene fluoride (PVDF) mesh in inlay position of the abdominal wall. After 8 weeks, mesh expansion and abdominal wall defect size were measured. Finally, pigs were euthanized and abdominal walls were explanted for histological and immunohistochemical assessment. Results: Eight weeks after abdominal wall replacement, transversal diameter of the fascial defect in the TPU group was significantly smaller than in the PVDF group (4.5 cm vs. 7.4 cm; p = 0.047). Immunhistochemical analysis showed increased Ki67 positive cells (p = 0.003) and a higher number of apoptotic cells (p = 0.047) after abdominal wall replacement with a TPU mesh. Collagen type I/III ratio was increased in the PVDF group (p = 0.011). Conclusion: Implantation of an elastic TPU mesh as abdominal wall inlay is a promising approach to reduce the size of the ventral hernia after open abdomen by mesh-mediated traction. However, this effect was associated with a slightly increased foreign body reaction in comparison to the nonelastic PVDF.

Long-term outcome and quality of life after initial and repeat resection of colorectal liver metastasis: A retrospective analysis.

BACKGROUND: Repeat hepatectomy is a widely accepted treatment for patients with recurrent colorectal liver metastasis (CRLM). The aim of this study was to compare initial and repeat hepatic resection concerning overall survival, prognostic factors and postoperative quality of life. METHODS: Data on patients who underwent initial or repeat hepatic resection for CRLM between 2010 and 2016 were prospectively collected and retrospectively evaluated. Follow-up data, EORTC QLQ-C30 and QLQ-LMC21 questionnaire results for quality of life (QoL) evaluation were analyzed. RESULTS: 160 patients at a median age of 62.8 ± 11.8 years were analyzed. 122 were initially resected and 38 underwent a repeat hepatic resection. Disease-free survival (DSF) was superior in the initial resection group (p < 0.001), while there was no difference in overall survival (OS) (p = 0.288). BMI >30 (p = 0.012), extrahepatic tumor manifestation (p = 0.037), >1 CRLM manifestation (p = 0.009), and perioperative chemotherapy (p = 0.006) in the initial resection group and primary left colon tumor (p = 0.001) in the repeat resection group were identified as prognostic factors in multivariate Cox regression analysis. EORTC QLQ-LMC-21 module symptom score displayed an increased occurrence of a dry mouth in the initial hepatectomy group (p = 0.003). EORTC QLQ-C30 general functioning and symptom scores showed no difference. CONCLUSION: Repeat hepatic resection for CRLM is as effective as primary surgical treatment in terms of OS and QoL. Patients should be selected carefully concerning prognostic factors as DFS is decreased after repeat hepatic resection.

Influence of continuous renal replacement therapy on cardiac output measurement using thermodilution techniques.

BACKGROUND: Acute renal failure (ARF) ranks among the most frequent complications in critically ill patients and continuous renal replacement therapy (CRRT) is a typical treatment regimen in intensive care patients. Contributing factors to ARF, such as septic shock and hemodynamic instability require extended hemodynamic monitoring, and the simultaneous use of CRRT and cardiac output measurement is common. In view of this, a systematic analysis of the interaction between CRRT and cardiac output measurements by thermodilution is warranted. Cardiac output (CO) is commonly measured with thermodilution-based methods in critically ill patients. The methods are accurate but the measurements are affected by inconstant indicator volumes or changes in blood temperature. Because continuous renal replacement therapy (CRRT) may alter blood volume and temperature, we investigated its effect on thermodilution-based CO measurement. METHODS: Thirty-two intensive care patients with both CRRT and CO monitoring were studied. Hemodynamic parameters were first measured in quintuple with bolus injections of cold saline during CRRT. Further five measurements were performed after CRRT had been shut off, and a final five measurements were performed after it had been restarted. Fifty measurement series were performed in patients with a pulmonary artery catheter and 25 in patients using a transpulmonary thermodilution method (PiCCO®). RESULTS: The first measurements in each series after switching CRRT off or on deviated most markedly from the average. When these measurements were excluded, the averaged CO values with and without CRRT differed significantly but by <7% (P<0.05). CONCLUSION: Substantial measurement error was only observed immediately after CRRT was switched off or on. Subsequent CO measurements did not depend on the CRRT status. Interrupting CRRT before measuring CO is not generally recommended, however, if interrupted, it is crucial to wait for blood temperature to reach a steady state before initiating the first measurements.

Body plethysmography--its principles and clinical use.

Body plethysmography allows to assess functional residual capacity (FRC(pleth)) and specific airway resistance (sRaw) as primary measures. In combination with deep expirations and inspirations, total lung capacity (TLC) and residual volume (RV) can be determined. Airway resistance (Raw) is calculated as the ratio of sRaw to FRC(pleth). Raw is a measure of airway obstruction and indicates the alveolar pressure needed to establish a flow rate of 1 L s(-1). In contrast, sRaw can be interpreted as the work to be performed by volume displacement to establish this flow rate. These measures represent different functional aspects and should both be considered. The measurement relies on the fact that generation of airflow needs generation of pressure. Pressure generation means that a mass of air is compressed or decompressed relative to its equilibrium volume. This difference is called "shift volume". As the body box is sealed and has rigid walls, its free volume experiences the same, mirror image-like shift volume as the lung. This shift volume can be measured via the variation of box pressure. The relationship between shift volume and alveolar pressure is assessed in a shutter maneuver, by identifying mouth and alveolar pressure under zero-flow conditions. These variables are combined to obtain FRC(pleth), sRaw and Raw. This presentation aims at providing the reader with a thorough and precise but non-technical understanding of the working principle of body plethysmography. It also aims at showing that this method yields significant additional information compared to spirometry and even bears a potential for further development.

[Preoperative prewarming as a routine measure. First experiences]. / Präoperative Vorwärmung in der klinischen Routine. Erste Erfahrungen.

BACKGROUND: Despite the broad application of intraoperative warming new studies still show a high incidence of perioperative hypothermia. Therefore a prewarming program in the preoperative holding area was started. METHODS: The efficacy of the prewarming program was assessed with an accompanying quality assurance check sheet over a period of 3 months. RESULTS: During the 3 month test period 127 patients were included. The median length from arrival in the holding area to beginning prewarming was 6 min and the average duration of prewarming was 46±38 min. During prewarming the core temperature rose by 0.3±0.4°C to 37.1±0.5°C and decreased to 36.3±0.5°C after induction of anesthesia. At the end of the operation the core temperature was 36.4±0.5°C and 14% of the patients were hypothermic. CONCLUSION: These data allow 2 conclusions: 1. Prewarming in the holding area is possible with a sufficient duration. 2. Prewarming is highly efficient even when performed over a relatively short duration.

Utility of cystatin C for assessment of renal function after cardiac surgery.

BACKGROUND: Though acute renal failure among cardiac surgery patients is associated with increased mortality, diagnosis of renal failure is often delayed due to the late detectability of laboratory markers for kidney failure. Recently, a number of clinical studies have shown that glomerular filtration rate (GFR) can be estimated by measuring the serum concentration of cystatin C (CysC). However, comparisons between the diagnostic effectiveness of CysC and serum creatinine have been inconsistent. The present study compares the diagnostic effectiveness of both serum markers in cardiac surgery patients. METHODS: In 50 cardiac surgery patients, GFR was quantified by measuring creatinine clearance and estimated from serum concentrations of both creatinine and CysC. The sensitivity and specificity of serum creatinine and CysC for detection of reduced GFR values were compared as well as correlation between estimated GFR values and creatinine clearance. RESULTS: GFR values <60 ml/min/1.73 m(2) were detected with equal effectiveness using creatinine or CysC, whereas for the detection of GFR <90 ml/min/1.73 m(2) the area under the curve of serum creatinine was significantly higher. Correlation between estimated GFR values and creatinine clearance was higher when creatinine-based formulae were used. CONCLUSION: In patients after cardiac surgery, CysC is not superior to serum creatinine for assessment of GFR.

[Teaching and simulation. Methods, demands, evaluation and visions]. / Lehre und Simulation. Methoden, Anforderungen, Evaluation und Visionen.

Since 1st October 2003 the new German "Approbationsordnung für Arzte" (Medical Licensing Regulations) requires an increasing amount of small group teaching sessions and encourages a multidisciplinary and more practical approach to the related topics. In 2004 the German Society of Anaesthesiology and Intensive Care Medicine has provided almost all anaesthesia faculties of German Universities with equipment for full-scale simulation. This article describes methods for a simulation-based medical education training program. Basic requirements for a successful training program using full scale simulators are the provision of an adequate logistical and material infrastructure, teacher attendance of train-the-trainer courses, implementation in the medical curriculum and an instructor-student ratio of 1:3, equivalent to that for bedside teaching. If these requirements were fulfilled, medical students scored the simulation scenarios "induction of anaesthesia", "acute pulmonary embolism", "acute management of a multiple trauma patient" and "postoperative hypotension" as 1.5, 1.6, 1.5 and 1.5, respectively, on a scale of 1-6. These scores were better than those given for other segments of the curriculum.

Dysregulation of TNF/TNFR superfamily members: a systemic link between intra- and extrathyroidal manifestations in Graves' disease.

Graves' disease (GD) coincides with the occurrence of disease-associated intrathyroidal dendritic cells (DC) and intraorbital inflammatory macrophages (Mphi). Physiologically, tumour necrosis factor-alpha (TNF-alpha) strongly affects the differentiation of DC and Mphi from monocytic precursors; we thus hypothesized that dysregulation of the TNF/TNFR superfamilies may provide a systemic pathogenic link in GD. In patients without eye symptoms, percentages of TNF-alpha-stimulated blood monocytes were highly significantly (P < 0.001) elevated, corresponding to both intrathyroidal DC maturation as well as increases in mature blood DC (MHC-II(hi)/CD40+/RFD1(hi)) and B cells (CD20(hi)/CD40+). GD patients also displaying eye symptoms revealed a striking reduction in blood monocytes, yet significantly (P < 0.05) increased CD40(hi) and TNF-alpha(hi) leucocytes. These findings suggest for GD that excess TNF-alpha induces monocytes to differentiate into hyperactivated thyroidal DC that, once emigrated, initiate systemic humoral autoimmunity associated with CD40/TNF-alpha upregulation. Such overexpression may instigate differentiation of periorbital inflammatory Mphi from CD14(hi)/CD16+ monocytes as a likely precursor subset. These results indicate that dysregulation of TNF/TNFR superfamily members provides a systemic pathogenic link in GD in that hyperactivated circulating monocytic precursors give rise to locally restricted, disease-associated DC and Mphi. Monocytes, therefore, may serve as a suitable target to therapeutically address the common precursor of key promoters of GD.

Leishmania major lipophosphoglycan modulates the phenotype and inhibits migration of murine Langerhans cells.

Langerhans cells (LC), members of the dendritic cell family, play a central role in the initiation and regulation of the immune response against the protozoan parasite Leishmania major. LC take up antigens in the skin and transport them to the regional lymph nodes for presentation to T cells. However, it is not known whether LC functions are modulated by parasite antigens. In the present study, we examined the effect of a major parasite surface molecule, L. major lipophosphoglycan (LPG), on the maturation of LC and their migratory properties. The results show that exposure to LPG did not affect the expression of major histocompatibility complex (MHC) class II and B7, but induced an up-regulation of CD25, CD31 and vascular endothelial (VE)-cadherin expression and a down-regulation of Mac-1 expression, by LC. Importantly, LPG treatment inhibited the migratory activity of LC, as it reduced their efflux from skin explants and their migration in transwell cultures. These results suggest that Leishmania LPG impairs LC migration out of the skin and thus may modulate their immunostimulatory functions, which require LC translocation from skin to lymph nodes.

In-vitro differentiation of mature dendritic cells from human blood monocytes.

Representing the most potent antigen-presenting cells, dendritic cells (DC) can now be generated from human blood monocytes. We recently presented a novel protocol employing GM-CSF, IL-4, and IFN-gamma to differentiate monocyte-derived DC in vitro. Here, such cells are characterized in detail. Cells in culture exhibited both dendritic and veiled morphologies, the former being adherent and the latter suspended. Phenotypically, they were CD1a-/dim, CD11a+, CD11b++, CD11c+, CD14dim/-, CD16a-/dim, CD18+, CD32dim/-, CD33+, CD40+, CD45R0+, CD50+, CD54+, CD64-/dim, CD68+, CD71+, CD80dim, CD86+/++, MHC class I++/ , HLA-DR++/ , HLA-DP+, and HLA-DQ+. The DC stimulated a strong allogeneic T-cell response, and further evidence for their autologous antigen-specific stimulation is discussed. Although resembling a mature CD11c+ CD45R0+ blood DC subset identified earlier, their differentiation in the presence of the Th1 and Th2 cytokines IFN-gamma and IL-4 indicates that these DC may conform to mature mucosal DC.

[Causes of failure and dangers in the use of motor driven infusion pumps. Accidental closure of the infusion system]. / Fehlerquellen und Gefahren beim Einsatz von Motorspritzenpumpen. Akzidenteller Verschluss des Infusionssystems.

UNLABELLED: Syringe drivers are used in anaesthetics, intensive care and emergency medicine to deliver small volumes of highly potent drugs with continuous, constant and reproducible flow. For early recognition of interruptions of the drug delivery caused by occlusion of the infusion system, an alarm is triggered as soon as the system pressure exceeds a certain limit. The sensitivity of this alarm depends on the flow rate, type-specific cut-off pressure and the elastic parameters of the infusion system. The sudden release of pressure built up in the system after occlusion occurred can cause delivery of an uncontrolled drug bolus and hence an additional hazard. METHODS: Six syringe drivers that are widely used in clinical practice were tested for alarm delay and bolus delivery in the event of an occlusion in the system. First, the alarm pressures at flow rates of 10, 50 and 100 ml/h were measured. Then the alarm delay time and bolus volumes post-occlusion were assessed, using a basic infusion system (syringe + single infusion set). Finally, several alterations to the system like extension, tap battery with germ filters or branching were made and their impact on alarm delay and bolus volume measured. RESULTS: Because of the great differences in alarm pressures between the devices tested, there were marked differences in the alarm delay at same flow rates. Predictably, there was an indirect proportional link between alarm delay and flow rate. Using the basic infusion system, alarm delays between 23 s and 143 min were measured. In two of the tested syringe drivers, a pressure-release mechanism is activated with the pressure alarm, which prevented bolus application. In the other devices, release of the pressure in the occluded system caused boli of 0.5-7 ml. Variations in the actual syringe volume and insertion of a second connection tube had no impact on alarm delay and bolus volume. Tap batteries, parallel running syringe drivers or trapped air in the system, however, caused marked increase in both alarm delay (107%) and bolus volume (+147%). DISCUSSION: Unidentified occlusions of the system cause grave malfunctioning of syringe drivers. While applying highly potent drugs, the discontinuation of drug delivery with subsequent bolus application can cause vital danger to the patient. As a result of the significant time delays in the pressure alarms, the devices tested do not provide sufficient protection against unrecognized system occlusion. Syringe drivers with adjustable alarm pressure can be set close to the actual infusion pressure. A further important point is that one should aim at a reduction in the elastic properties of the infusion set because of the great impact on alarm delay and bolus volume.

[Severe, accidental hypothermia: active rewarming with a simple extracorporeal veno-venous warming-circuit]. / Schwere, akzidentelle Hypothermie: Aktive Wiedererwärmung durch einen einfachen extrakorporalen veno-venösen Wärmekreislauf.

We report the case of a 35-year-old male who was admitted to the intensive care unit because of somnolence due to accidental hypothermia. Initial examination showed a Glasgow coma score of 10 and a rectal temperature of 27.4 degrees C. Because of stable circulatory conditions, there was no mandatory indication for rewarming by means of cardiopulmonary bypass. We rewarmed the patient with an extracorporeal veno-venous haemofiltration device combined with a countercurrent fluid warmer. An average increase in body temperature of 1.34 degrees Ch-1 could be obtained. We conclude that the described technique represents an effective and well-controllable method for treatment of hypothermia in patients with stable haemodynamic conditions. Because of the availability of the required equipment, this method can also be practised in hospitals without cardiac surgical departments and cardiopulmonary bypass facilities.

[Tamm-Horsfall protein, alpha-1- and beta-2-microglobulin as kidney function markers in heart surgery]. / Tamm-Horsfall-Protein, alpha 1- und beta 2-Mikroglobulin als Nierenfunktionsmarker in der Herzchirurgie.

After cardiac surgery, transient renal dysfunction often occurs. Regional differentiation of these processes is possible only using invasive techniques, including renal biopsy. Approximately 30 different plasma protein components have been identified in the urine of healthy individuals by means of qualitative and quantitative immunochemical methods. The detection of microalbuminuria has high diagnostic relevance for the early diagnosis of renal damage at a reversible stage. One typical urinary protein is Tamm-Horsfall protein (THp). After histochemical staining of human kidney sections, activity is seen in the loop of Henle and initial distal tubule. The assay of alpha-1 microglobulin (MG) in urine is considered one of the most efficient laboratory parameters for the diagnosis of tubular lesions. Serum concentrations of alpha-1 MG are less dependent on extrarenal changes than are those of other low-molecular-weight proteins. beta-2 MG is also one of the standards used in recent years for diagnostic relevance. Urinary albumin excretion, normally less than 30 mg per day, sometimes increases after glomerular damage. Some renal function tests are used daily in many intensive care units, e.g. creatinine clearance (CCr) or urea and sodium excretion. Renal dysfunction should, however, be further examined to localise regional damage and to seek new clinical standards in addition to the conventional tests. METHODS. After obtaining the agreement of the local ethics committee, 30 patients were divided into two groups of 15 each: group I without renal dysfunction and CCr more than 60 ml/min; and group II with CCr below 60 ml/min. THp and alpha-1 MG were measured pre- and postoperatively after open heart surgery with the ELISA and beta-2 MG with the nephelometric technique. These parameters were compared with clinical standards such as albumin excretion, blood urea nitrogen (BUN), urea clearance, and fractional sodium excretion. RESULTS. The CCr did not change in group I from the pre- to postoperative period (81.5 to 85.1 and 91.4 ml/min), nor did excretion of THp (20.1 to 25.0 and 24.8 mg/day), correlation r = 0.7; P < 0.001). The elimination of alpha-1 and beta-2 MG was significantly higher in the postoperative period in this group (alpha-1: 7.2 to 44.1 and 100.6 mg/day; beta-2: 0.3 to 2.1 and 3.2 mg/day). In group II CCr showed pathological values (36.8 to 31.1 and 36.3 ml/min), as did simultaneous THp (13.5 to 9.7 and 12.7 mg/day). alpha-1 and beta-2 MG values became more pathological in the postoperative period than in group I (alpha-1: 32.8 to 113.9 and 198.5 mg/day; beta-2: 0.7 to 5.8 and 16.9 mg/day). DISCUSSION. Measurement of the excretion of THp and alpha-1 and beta-2 MG is a useful addition to present clinical standards for recognising early changes in renal function. The increases in the postoperative period after cardiac surgery showed tubular damage even in patients without predictive risk factors or clinical signs. In patients with renal dysfunction open heart surgery and extracorporeal circulation led to significant tubular damage.

[The histamine provocation test: are 1 second capacity and specific conductance competing or complementary measurement values?]. / Histaminprovokationstest: Sind Einsekundenkapazität und spezifische Conductance konkurrierende oder einander ergänzende Messwerte?

We tested criteria for the decision, whether a provocation challenge with histamine is positive. The combination of spirometry and bodyplethysmography by the condition sGaw less than or equal to 0.04 x PC-FEV overcomes the contradictions due to conventional criteria as PC-FEV greater than or equal to 20% or PC-sGaw greater than or equal to 50%.

[Clinical use of an expert system for interpreting lung function tests--relation of results to the respective examiner]. / Klinische Anwendung eines Expertensystems zur Interpretation von Lungenfunktionsprüfungen--Abhängigkeit der Ergebnisse vom jeweiligen Anwender.

We used a new expert system for interpretation of lung function tests to check the differences between four investigators. The data base of the program system consists of vectors which yield statistical informations concerning the decisions of the users.

An expert system for synoptic interpretation of lung function tests.

We simulate the interpretation process by the testing of preformed working hypotheses. A clinical syndrome, "bronchial obstruction," is described by a set of suitable parameters (FEV1, MMEF, Raw, etc.). For a given patient, this set forms a normalized vector. It has to be compared with equivalent data derived from patients which fulfilled the criteria for the clinical syndrome in question. If the patient's vector has a similar direction as the vector of the collective, the working hypothesis is accepted. The length of the vector is then used to quantify the severity of the functional disturbances in verbal terms ("slight," "moderate," "severe"). The limits used for severity grading and the typical parameter pattern for the given syndrome are adapted to the user's criteria by a built-in learning capability. On the other hand, the assembled data may be used for the training of newcomers. The use of vector algorithms allows for a high flexibility of our program with respect to all methods used in lung function testing.