Perioperative management of positioning in gynecological cancersurgery: a national NOGGO-AGO intergroup survey.

INTRODUCTION: The daily clinical routine in the operating room includes patient positioning. The number of perioperative positioning-related complications is growing, along with the legal proceedings concerning this topic, and only a few guidelines exist to provide specific recommendations. The aim of this survey was to assess perioperative positioning and associated adverse events during gynecological cancer surgery in Germany. METHODS: A total of 633 gynecological departments of primary, secondary, and maximum healthcare hospitals in Germany were invited to participate in this multiple-choice online questionnaire. The survey was conducted anonymously for a period of six months. The survey was divided into five different sections: descriptive information about the respondent department, pre- and postoperative management, management of positioning in the operating room based on two fictional case examples, and quality management. RESULTS: The response rate of our survey was 29.1 % (184/633). Nearly half of the departments (46.7 %) reported to have had one to five patients with positioning-related complications during the prior 12 months, and 29.1 % had experienced a legal dispute due to positioning-related complications. Departments with more than 50 gynecologic-oncological surgeries per year more often reported positioning-related complications (p=0.003). Standard operating procedures exist in almost every department for laparoscopic (97 %) and open surgery (95.1 %), respectively. DISCUSSION: The high number of positioning-related complications throughout all departments of different healthcare levels underlines the relevance of this issue and supports the need for a prospective European registry for further analysis. Training and education for all staff members should be routinely implemented to reduce and prevent positioning-related complications.

Current practice and physicians' opinion about preoperative hair removal as a part of ERAS pathway implementation in gynecology and gynecology-oncology: a NOGGO-AGO survey of 148 gynecological departments in Germany.

PURPOSE: To gather standardized information about current practices and doctors' opinions on preoperative hair removal (PHR) from the surgical site and to evaluate the extent of PHR as one of the elements of enhanced recovery after surgery (ERAS) pathways that is established in the clinical routine in gynecology and gynecology-oncology departments in Germany. METHODS: We performed a nationwide survey among 638 primary, secondary and tertiary health care gynecological departments in Germany. Data were obtained by sending a multiple-choice questionnaire about preoperative management of hair removal. The authors also evaluated the awareness of doctors regarding PHR as well as the method and time frames of PHR. The results were compared to the existing standard of procedure (SOP) and guidelines. RESULTS: 148 units (23.2%) took part in the survey; participants in the survey were mostly chief physicians in 47.3% of the cases. Half (50.7%) of all the responses came from certified gynecological cancer centers. A SOP regarding PHR was reported as present in 113 clinics (76.4%). 83.8% of all units are performing PHR for midline laparotomy, 52.7% in laparoscopic operations, and 45.3% in vaginal operations. 48% used a clipper, while 43.2% utilized a single-use razor. 56.1% shaved instantly before the operation, whereas 35.8% did it the day before and earlier. 40.3% of chief physicians believe that PHR causes more surgical site infections (SSI) compared to only 11.5% of junior doctors. CONCLUSION: PHR in gynecological departments in Germany is performed very heterogeneously and SOPs are often not based on guidelines and ERAS principles. Around one-third of the German gynecological clinics keep strictly to the guidelines. The awareness on PHR and SSI among junior doctors is very low.

European trainee exchange: experiences due the ENTOG exchange programme 2015 in Utrecht, the Netherlands.

BACKGROUND: The European Network of Trainees in Obstetrics and Gynaecology (ENTOG) is a Europe wide association of trainees in gynaecology and obstetric. It is closely associated with the European Board and College of Obstetrics and Gynaecology. Both organisations aim to improve the training in gynaecology and obstetrics as the fundamental step to overcome large differences in women's health across Europe. Annually, ENTOG meeting takes place which brings together trainees from the member countries to share their professional experience. The training session of the meeting which is preceded by an exchange programme. The exchange programme aims to learn something about the everyday work of the host country. METHOD: This article reports about the ENTOG exchange program that took place in the Netherlands this year and outlines difference to the German health system. RESULT AND PERSPECTIVE: The inter-collegiate exchange within Europe represents both a challenge as well as an opportunity to learn from each other. The 2016 ENTOG exchange will take place in Turkey.

Effects of chronic SDMA infusion on glomerular filtration rate, blood pressure, myocardial function and renal histology in C57BL6/J mice.

BACKGROUND: Symmetrical dimethylarginine (SDMA), the structural isomer of the nitric oxide synthase inhibitor asymmetrical dimethylarginine, has long been regarded as an inert substance. Recent epidemiological and preclinical data suggest that it might be involved in the pathophysiology of renal and cardiovascular diseases. Therefore, we aimed to investigate the effect of chronic SDMA infusion on renal and cardiac function in mice. METHODS: Eight-week-old male C57Bl/6 mice received vehicle-controlled infusion of SDMA (250 µmol/kg/days) for 28 days using osmotic minipumps (n = 24/group). The following parameters were monitored: glomerular filtration rate (GFR; fluoresceinyl thiocarbamoyl-inulin excretion kinetic), cardiac function (echocardiography) and blood pressure (tail cuff). Blood samples for SDMA determination were obtained at baseline, 2 and 4 weeks. Mice were euthanized at 4 weeks to obtain tissue for renal histology. RESULTS: Chronic SDMA infusion led to a significant increase of SDMA levels from 0.26 ± 0.10 to 3.49 ± 1.66 µmol/L (P < 0.001) at 4 weeks. Despite this SDMA increase, the GFR did not change (1224 ± 351 versus 1017 ± 345 mL/min/g body weight, n.s.) at 4 weeks, when compared with baseline. We did not find any histological changes, particularly no effect on fibrosis or endothelias nitric oxide synthase expression. There was neither an effect of SDMA on systolic blood pressure (106 ± 12 versus 111 ± 18 mmHg, n.s.) nor on ejection fraction (54.2 ± 1.7 versus 58.4 ± 1.9%, n.s.). CONCLUSIONS: Based on our experiments, it seems unlikely that chronically elevated SDMA alone has an effect on renal and cardiac function in otherwise healthy mice. Future studies have to clarify the potential pathophysiological role of SDMA in cardiovascular disease.

Unilateral nephrectomy causes an abrupt increase in inflammatory mediators and a simultaneous decrease in plasma ADMA: a study in living kidney donors.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthases (NOS). Reducing inducible NOS activity in acute inflammation seems to be desirable. In vitro data show that ADMA increases in response to inflammatory mediators, yet the effect of acute inflammation in vivo is scarcely studied. The aim of the study was to evaluate ADMA plasma levels before, during, and after the acute (nonbacterial) inflammatory-like state. Plasma ADMA, l-arginine, C-reactive protein, and IL-6 were determined in 24 healthy subjects undergoing living related kidney donation before as well as 1, 6, 12, 24, 72, and 168 h thereafter. Six hours after nephrectomy, ADMA levels decreased compared with baseline (0.488 ± 0.075 vs. 0.560 ± 0.060 µmol/l, P < 0.05). This difference became even more marked 24 h after the operation (0.478 ± 0.083 µmol/l, P < 0.01 vs. baseline), when the proinflammatory cytokine IL-6 peaked. Seven days after unilateral nephrectomy, ADMA levels were elevated above baseline (0.63 ± 0.05 µmol/l, P < 0.001 vs. baseline). l-Arginine levels decreased already 1 h after nephrectomy (97.5 ± 22.5 µmol/l, P < 0.01 vs. baseline) and paralleled the change in ADMA thereafter. At the end of the observation period when inflammation markers were regressing, l-arginine levels were significantly elevated above baseline (160.6 ± 25.1 µmol/l, P < 0.001 vs. baseline). In summary, this is the first study showing that both ADMA and l-arginine decrease temporarily after unilateral nephrectomy coinciding with the increase in inflammatory mediators. The l-arginine/ADMA ratio, a surrogate for NO production capacity, was only altered for <24 h.

SDMA is an early marker of change in GFR after living-related kidney donation.

BACKGROUND: Early detection of changes in the glomerular filtration rate (GFR) is crucial in detecting acute kidney injury. There is burgeoning evidence from preclinical and clinical studies that symmetrical dimethylarginine (SDMA) correlates well with different parameters of renal function. In some studies, SDMA even outperformed creatinine as a marker of GFR. It is however unknown how fast SDMA is increasing after reduction in GFR. The aim of our study was therefore to determine the temporal change of SDMA in comparison with cystatin C after a defined reduction in GFR. METHODS: Blood samples from 24 healthy living-related kidney donors (19 F/5 M), mean age 55.2 ± 8.3 years, were collected prior to donation of the kidney as well as 1, 6, 12, 24, 72 and 168 h after unilateral nephrectomy. SDMA levels were measured using a liquid chromatography-mass spectrometry-based method. RESULTS: Within 6 h after unilateral nephrectomy, i.e. reduction of GFR by 50%, SDMA rose from 0.571 ± 0.120 to 0.659 ± 0.135 µmol/L (P < 0.001). Baseline cystatin C levels increased from 0.87 ± 0.16 to 1.07 ± 0.15 mg/L (P < 0.001). Also, serum creatinine rose significantly within 6 h after removal of one kidney from 65.4 ± 8.4 to 88.8 ± 10.2 µmol/L (P < 0.001). DISCUSSION: SDMA might be a valuable and early marker of change in GFR in the clinical and experimental setting. Future studies will have to clarify whether sensitivity, specificity and temporal resolution of SDMA make it an attractive candidate for the assessment of renal function in both the experimental and clinical setting.

Circulating levels of osteopontin are closely related to glomerular filtration rate and cardiovascular risk markers in patients with chronic kidney disease.

BACKGROUND: The pleiotropic cytokine osteopontin (OPN) is thought to be involved in the pathogenesis of atherosclerosis. However, the relationship between OPN and renal function, a cardiovascular risk factor itself, is not known. Therefore, we assessed the relationship between OPN plasma levels and renal function in patients at different stages of chronic kidney disease (CKD). METHODS: We studied 49 non-diabetic and non-smoking patients with primary kidney disease at different CKD stages (K/DOQI 1-5). True glomerular filtration rate (GFR) in patients was assessed using the inulin-clearance technique. To examine the role of an abrupt change in GFR on circulating OPN, 15 living related kidney donors were studied before and after unilateral nephrectomy. Twenty matched non-smoking healthy subjects served as controls. RESULTS: OPN plasma levels in patients with CKD stage 1 (i.e. GFR above 90 mL min(-1) 1.73 m(-2)) were comparable with controls. OPN levels increase in a linear fashion with declining GFR (r = -0.9, P < 0.0001), so that the increase in OPN mirrors the severity of renal impairment. After unilateral nephrectomy, circulating OPN increased significantly in parallel to the decrease in GFR. We found a direct association between OPN and other markers of renal function (serum-creatinine, homocysteine and symmetric dimethylarginine,) as well as with cardiovascular risk factors such as asymmetric dimethylarginine (r = 0.36, P = 0.0213). CONCLUSION: There is a close inverse association between GFR and circulating OPN in patients with CKD. Furthermore, OPN plasma levels correlate with established cardiovascular risk markers in patients with CKD. Assessment of renal function is important for the interpretation of OPN levels in patients with atherosclerotic disease.

Asymmetric dimethylarginine and symmetric dimethylarginine: axis of evil or useful alliance?

Almost 40 years ago, in 1970, Kakimoto and Akazawa were the first to isolate and describe N-N, N-G- and N-G,N'-G-dimethyl-arginine from human urine. Today, these substances are known as asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). In their detailed and meticulous publication, Kakimoto and Akazawa speculated about these two compounds: "They may have functional importance in proteins in which they are formed. If they are excreted into the urine as metabolites of body proteins, amounts of these substances in human urine may reflect methylation rate of body proteins and their turnover rates and determination of these substances might be important for the study of various pathological states." The following decades proved them to be right. ADMA, the most potent endogenous nitric oxide synthase (NOS) inhibitor was first found to be elevated in hemodialysis patients. It has been shown to correlate with traditional and nontraditional cardiovascular risk factors. ADMA is also a strong predictor of cardiovascular events and death in both patients with chronic kidney disease (CKD, stage 2-5) and in the general population. Moreover, ADMA predicts the progression of CKD. SDMA, the structural isomer of ADMA, has been shown to be an excellent marker of renal function in human and animal studies. There is emerging evidence that SDMA might also be involved in inflammation and atherosclerosis although it is only thought to be a (weak) indirect inhibitor of NOS. There is burgeoning evidence that these two substances may indeed damage normal physiological functions, or interfere with physiological defense mechanisms in CKD, play a role in the progression of renal disease, induce uremic symptoms, and may even contribute to dialysis-related complications. Hence these compounds are considered uremic toxins. This review summarizes our current concept how these two compounds might play a crucial part in the pathophysiology of uremia, either alone or in their combination. We also allude to the potential physiological role these substances might have.