Kidney transplantation is associated with harmful processes affecting the viability of the graft. One of these processes is associated with the phenomenon of ischaemia–reperfusion injury. Anaesthetic ...conditioning is a widely described strategy to attenuate ischaemia–reperfusion injury. We therefore conducted the Volatile Anaesthetic Protection of Renal Transplants-1 trial, a pilot project evaluating the influence of two anaesthetic regimens, propofol- vs sevoflurane-based anaesthesia, on biochemical and clinical outcomes in living donor kidney transplantation.
Sixty couples were randomly assigned to the following three groups: PROP (donor and recipient propofol), SEVO (donor and recipient sevoflurane), and PROSE (donor propofol and recipient sevoflurane). The primary outcome was renal injury reflected by urinary biomarkers. The follow-up period was 2 yr.
Three couples were excluded, leaving 57 couples for analysis. Concentrations of kidney injury molecule-1 (KIM-1), N-acetyl-β-d-glucosaminidase (NAG), and heart-type fatty acid binding protein (H-FABP) in the first urine upon reperfusion showed no differences. On day 2, KIM-1 concentrations were higher in SEVO 952.8 (interquartile range 311.8–1893.0) pg mmol−1 compared with PROP 301.2 (202.0–504.7) pg mmol−1. This was the same for NAG: SEVO, 1.835 (1.162–2.457) IU mmol−1vs PROP, 1.078 (0.819–1.713) IU mmol−1. Concentrations of H-FABP showed no differences. Measured glomerular filtration rate at 3, 6, and 12 months showed no difference. After 2 yr, there was a difference in the acute rejection rate (P=0.039). Post hoc testing revealed a difference between PROP (35%) and PROSE (5%; P=0.020). The difference between PROP and SEVO (11%) was not significant (P=0.110).
The SEVO group showed higher urinary KIM-1 and NAG concentrations in living donor kidney transplantation on the second day after transplantation. This was not reflected in inferior graft outcome.
NCT01248871.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
OBJECTIVES: To examine the effects of general anesthesia on the risk of incident postoperative delirium in older adults undergoing hip surgery.
DESIGN: Secondary analysis of haloperidol prophylaxis ...for delirium clinical trial data. Predefined risk factors for delirium were assessed prior to surgery. Primary outcome was postoperative delirium. Study outcome was compared across patient groups who received either general or regional anesthesia, and for individuals receiving various perioperative medications (benzodiazepines, anticholinergics, and opioids), using multivariable logistic regression after controlling for potential confounders. Subgroup analyses based on baseline cognitive impairment and delirium risk were also undertaken.
SETTING: Large medical school‐affiliated general hospital in Alkmaar, the Netherlands.
PARTICIPANTS: Five hundred twenty‐six adults aged 70 and older undergoing hip surgery.
MEASUREMENTS: The primary outcome was the incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria).
RESULTS: Sixty participants (11.4%) had incident postoperative delirium. One hundred eighty‐nine (35.9%) received general anesthesia, 18 (9.5%) of whom developed postoperative delirium, and 337 (64.1%) received regional anesthesia, 42 (12.5%) of whom developed postoperative delirium (adjusted odds ratio=0.81, 95% confidence interval=0.43–1.52, P=.51). Results were stratified for baseline cognitive impairment, age, acute admission, perioperative medication and other delirium risk factors. Delirium was not independently associated with specific drugs or the medication classes opioids, benzodiazepines, and anticholinergics.
CONCLUSION: General anesthesia has no distinct effect on incident postoperative delirium in older adults undergoing hip surgery. This also holds for individuals suffering from cognitive impairment or who are otherwise at risk for postoperative delirium. Perioperative use of narcotics, benzodiazepines, and anticholinergic agents was not associated with incident delirium in this cohort of older adults undergoing hip surgery.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Electrically induced birefringence experiments were performed on dispersions consisting of sulfate latex nanospheres of two different sizes and charges dispersed in an electrolyte solution, at ...various ionic strengths. The induced birefringence was found to have an important contribution increasing as a quadratic power law of the volume fraction of the spheres. This shows that interparticle interactions play a role in the observed birefringence. The data were analyzed, using a theory from Hafkenscheid and Vlieger Physica 75 (1974) 57, in terms of the changes of the interparticle separations in the directions parallel and perpendicular to the applied electric field.
Electrically induced birefringence experiments were performed on dispersions consisting of sulfate latex nanospheres of two different sizes and charges dispersed in an electrolyte solution, at various ionic strengths. The induced birefringence was found to have an important contribution increasing as a quadratic power law of the volume fraction of the spheres. This shows that interparticle interactions play a role in the observed birefringence. The data were analyzed, using a theory from Hafkenscheid and Vlieger Physica 75 (1974) 57, in terms of the changes of the interparticle separations in the directions parallel and perpendicular to the applied electric field.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Organic acidurias (OAD) and urea‐cycle disorders (UCD) are rare inherited disorders affecting amino acid and protein metabolism. As dietary practice varies widely, we assessed their long‐term ...prescribed dietary treatment against published guideline and studied plasma amino acids levels. We analyzed data from the first visit recorded in the European registry and network for intoxication type metabolic diseases (E‐IMD, Chafea no. 2010 12 01). In total, 271 methylmalonic aciduria (MMA) and propionic aciduria (PA) and 361 UCD patients were included. Median natural protein prescription was consistent with the recommended daily allowance (RDA), plasma L‐valine (57%), and L‐isoleucine (55%) levels in MMA and PA lay below reference ranges. Plasma levels were particularly low in patients who received amino acid mixtures (AAMs‐OAD) and L‐isoleucine:L‐leucine:L‐valine (BCAA) ratio was 1.0:3.0:3.2. In UCD patients, plasma L‐valine, L‐isoleucine, and L‐leucine levels lay below reference ranges in 18%, 30%, and 31%, respectively. In symptomatic UCD patients who received AAM‐UCD, the median natural protein prescription lay below RDA, while their L‐valine and L‐isoleucine levels and plasma BCAA ratios were comparable to those in patients who did not receive AAM‐UCD. Notably, in patients with ornithine transcarbamylase syndrome (OTC‐D), carbamylphosphate synthetase 1 syndrome (CPS1‐D) and hyperammonemia‐hyperornithinemia‐homocitrullinemia (HHH) syndrome selective L‐citrulline supplementation resulted in higher plasma L‐arginine levels than selective L‐arginine supplementation. In conclusion, while MMA and PA patients who received AAMs‐OAD had very low BCAA levels and disturbed plasma BCAA ratios, AAMs‐UCD seemed to help UCD patients obtain normal BCAA levels. In patients with OTC‐D, CPS1‐D, and HHH syndrome, selective L‐citrulline seemed preferable to selective L‐arginine supplementation.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed ...to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR).
This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests.
The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively).
In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The sedimentary succession along the Belaya River (North Caucasus) provides a record of middle Eocene to Miocene sediments. This time interval is well known for its important climatic transitions ...(e.g., Middle Eocene Climate Optimum (MECO) and Eocene-Oligocene Transition (EOT)), and changes in basin configuration from Peri-Tethys to Paratethys. The Belaya section contains two intervals marked by oxygen-depleted sediments; the Eocene Kuma Formation of the Peri-Tethys and the Oligocene Maikop Group of the Paratethys. Both are considered important source rocks for hydrocarbon exploration in the Black Sea and Caspian Sea. We present integrated stratigraphic results of the Belaya River section using calcareous nannoplankton biostratigraphy, magnetostratigraphy and 40Ar/39Ar dating. Furthermore, we investigate the geochemical character of the sediments using X-ray fluorescence (XRF) and stable carbon and oxygen isotopes. A middle Eocene age for the lower part of the succession is established from nannoplankton biostratigraphy. The Kuma Formation is dated between 42.1 and 38.4 Ma based on the assumption of constant sediment accumulation rates. A negative oxygen isotope excursion in the middle part of the Kuma Formation could be related to the MECO (~40 Ma). The onset of the Maikop Group is dated around the base of chron C13n at an age of ~33.7 Ma, close to the Eocene-Oligocene boundary. Based on geochemical results, we show that the Kuma Formation and Maikop Group correspond to two different episodes of intensified oceanic oxygen depletion in the succession. We hypothesise that oxygen-depletion as recorded in the Kuma Formation is linked to an increased nutrient input in the open marine Peri-Tethys due to widespread volcanism in the Neotethys subduction zone, while oxygen-depletion as recorded in the Maikop Group is linked to basin restriction caused by the eustatic sea-level fall straddling the Eocene – Oligocene boundary triggering stratified conditions in the semi-isolated Paratethys Sea.
•Integrated stratigraphy from Eocene to Oligocene at the Maikop group type section.•Section comprises sedimentary record through important climate transitions.•XRF results indicate two oxygen-depleted episodes in the succession.•Section contains the Middle Eocene Climatic Optimum in oxygen-depleted sediments.•Succession is probably continuous through Eocene-Oligocene transition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Small synthetic molecules termed growth hormone secretagogues (GHSs) act on the pituitary gland and the hypothalamus to stimulate and amplify pulsatile growth hormone (GH) release. A heterotrimeric ...GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. On the basis of its pharmacological and molecular characterization, this GPC-R defines a neuroendocrine pathway for the control of pulsatile GH release and supports the notion that the GHSs mimic an undiscovered hormone.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Recombinant human erythropoietin (rhEPO) is receiving increasing attention as a potential therapy for prevention of injury and restoration of function in nonhematopoietic tissues. However, the ...minimum effective dose required to mimic and augment these normal paracrine functions of erythropoietin (EPO) in some organs (e.g., the brain) is higher than for treatment of anemia. Notably, a dose-dependent risk of adverse effects has been associated with rhEPO administration, especially in high-risk groups, including polycythemia- hyperviscosity syndrome, hypertension, and vascular thrombosis. Of note, several clinical trials employing relatively high dosages of rhEPO in oncology patients were recently halted after an increase in mortality and morbidity, primarily because of thrombotic events. We recently identified a heteromeric EPO receptor complex that mediates tissue protection and is distinct from the homodimeric receptor responsible for the support of erythropoiesis. Moreover, we developed receptor-selective ligands that provide tools to assess which receptor isoform mediates which biological consequence of rhEPO therapy. Here, we demonstrate that rhEPO administration in the rat increases systemic blood pressure, reduces regional renal blood flow, and increases platelet counts and procoagulant activities. In contrast, carbamylated rhEPO, a heteromeric receptor-specific ligand that is fully tissue protective, increases renal blood flow, promotes sodium excretion, reduces injury-induced elevation in procoagulant activity, and does not effect platelet production. These preclinical findings suggest that nonerythropoietic tissue-protective ligands, which appear to elicit fewer adverse effects, may be especially useful in clinical settings for tissue protection.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Patients with methylmalonic acidemia (MMA) and propionic acidemia (PA) and urea cycle disorders (UCD), treated with a protein restricted diet, are prone to growth failure. To obtain optimal growth ...and thereby efficacious protein incorporation, a diet containing the essential and functional amino acids for growth is necessary. Optimal growth will result in improved protein tolerance and possibly a decrease in the number of decompensations. It thus needs to be determined if amino acid deficiencies are associated with the growth retardation in these patient groups. We studied the correlations between plasma L-arginine levels, plasma branched chain amino acids (BCAA: L-isoleucine, L-leucine and L-valine) levels (amino acids known to influence growth), and height in MMA/PA and UCD patients.
We analyzed data from longitudinal visits made in stable metabolic periods by patients registered at the European Registry and Network for Intoxication Type Metabolic Diseases (E-IMD, Chafea no. 2010 12 01).
In total, 263 MMA/PA and 311 UCD patients were included, all aged below 18 years of age. In patients with MMA and PA, height z-score was positively associated with patients' natural-protein-to-energy prescription ratio and their plasma L-valine and L-arginine levels, while negatively associated with the amount of synthetic protein prescription and their age at visit. In all UCDs combined, height z-score was positively associated with the natural-protein-to-energy prescription ratio. In those with carbamylphosphate synthetase 1 deficiency (CPS1-D), those with male ornithine transcarbamylase deficiency (OTC-D), and those in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome subgroup, height z-score was positively associated with patients' plasma L-leucine levels. In those with argininosuccinate synthetase deficiency (ASS-D) and argininosuccinate lyase deficiency (ASL-D), height was positively associated with patients' plasma L-valine levels.
Plasma L-arginine and L-valine levels in MMA/PA patients and plasma L-leucine and L-valine levels in UCD patients, as well as the protein-to-energy prescription ratio in both groups were positively associated with height. Optimization of these plasma amino acid levels is essential to support normal growth and increase protein tolerance in these disorders. Consequently this could improve the protein-to-energy intake ratio.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
The aim of this study was to evaluate whether a relation exists between surgical expertise and incidence of chronic postoperative inguinal pain (CPIP) after inguinal hernia repair using the ...Lichtenstein procedure .
Background
CPIP after inguinal hernia repair remains a major clinical problem despite many efforts to address this problem. Recently, case volume and specialisation have been found correlated to significant improvement of outcomes in other fields of surgery; to date these important factors have not been reviewed extensively enough in the context of inguinal hernia surgery.
Methods
A systematic literature review was performed to identify randomised controlled trials reporting on the incidence of CPIP after the Lichtenstein procedure and including the expertise of the surgeon. Surgical expertise was subdivided into expert and non-expert.
Results
In a total of 16 studies 3086 Lichtenstein procedures were included. In the expert group the incidence of CPIP varied between 6.9 and 11.7 % versus an incidence of 18.1 and 39.4 % in the non-expert group. Due to the heterogeneity between groups no statistical significance could be demonstrated.
Conclusion
The results of this evaluation suggest that an association between surgical expertise and CPIP is highly likely warranting further analysis in a prospectively designed study.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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