Background
Postoperative cognitive dysfunction (POCD) is a common complication in older patients with cancer and is associated with decreased quality of life and increased disability and mortality ...rates. Systemic inflammation resulting in neuroinflammation is considered important in the pathogenesis of POCD. The aim of this study was to explore the association between the early surgery‐induced inflammatory response and POCD within 3 months after surgery in older cancer patients.
Methods
Patients ≥65 years in need of surgery for a solid tumor were included in a prospective cohort study. Plasma levels of C‐reactive protein (CRP), interleukin‐1 beta (IL‐1β), IL‐6, IL‐10, and Neutrophil gelatinase‐associated lipocalin (NGAL) were measured perioperatively. Cognitive performance was assessed preoperatively and 3 months after surgery. POCD was defined as a decline in cognitive test scores of ≥25% on ≥2 of five tests within the different cognitive domains of memory, executive functioning, and information processing speed. Logistic regression analysis was performed.
Results
POCD was observed in 44 (17.7%) of 248 included patients. Age >75, preoperative Mini‐Mental State Examination (MMSE) score ≤26 and major surgery were independent significant predictors for POCD. In multivariate logistic regression analysis, no significant associations were shown between the early surgery‐induced inflammatory response and either POCD or decline within the different cognitive domains.
Conclusions
This study shows that one out of six older patients with cancer developed POCD within 3 months after surgery. The early surgery‐induced inflammatory response was neither associated with POCD, nor with decline in the separate cognitive domains. Further research is necessary for better understanding of the complex etiology of POCD.
Summary
Currently, there are no tools to predict postsurgery outcome after kidney transplantation. This study assesses whether frailty influence 30‐day postoperative complications after kidney ...transplantation. One‐hundred and fifty kidney transplantations were prospectively included. Frailty was assessed using a frailty indicator, consisting of 15 questions, covering most domains of functioning. Postoperative complications were measured by the Comprehensive Complication Index (CCI). Using a linear regression model, 30‐day postoperative complications and frailty correlation were adjusted for confounders, including sex, age, ASA Score, Charlson Comorbidity Index, hypertension, BMI, smoking, dialysis, duration of dialysis, type of transplantation, and retransplantation. The mean frailty score was 2.07(±1.6) and 23 patients were classified as frail (GFI ≥4). The mean CCI‐score was 18(±15.6), the mean CCI‐score for “frail” patients 30.1(±17.2) compared to 15.5 (±14.2) for “non‐frail” patients (N = 116). In a regression analysis, a significant relationship between CCI‐score and frailty (β = 13.3; 95% CI 5.7–20.9; P = 0.0007) and transplantation type (β = 4.9; 95% CI: 0.72–9.16; P = 0.02) was found, independent of confounders. In conclusion, frailty and type of transplantation are independent factors associated with an increased risk of postoperative complications.
Ischemia and reperfusion injury (IRI) is a complex pathophysiological phenomenon, inevitable in kidney transplantation and one of the most important mechanisms for non- or delayed function ...immediately after transplantation. Long term, it is associated with acute rejection and chronic graft dysfunction due to interstitial fibrosis and tubular atrophy. Recently, more insight has been gained in the underlying molecular pathways and signalling cascades involved, which opens the door to new therapeutic opportunities aiming to reduce IRI and improve graft survival. This review systemically discusses the specific molecular pathways involved in the pathophysiology of IRI and highlights new therapeutic strategies targeting these pathways.
Sevoflurane, a sigh of relief in COVID-19? Nieuwenhuijs-Moeke, Gertrude J.; Jainandunsing, Jayant S.; Struys, Michel M.R.F.
British journal of anaesthesia,
08/2020, Letnik:
125, Številka:
2
Journal Article
Early markers to predict delayed kidney graft function (DGF) may support clinical management. We studied the ability of four biomarkers (neutrophil gelatinase associated lipocalin (NGAL), liver-type ...fatty acid-binding protein (L-FABP), cystatin C, and YKL-40) to predict DGF after deceased donor transplantation, and their association with early graft function and GFR at three and twelve months.
225 deceased donor kidney transplant recipients were included. Biomarkers were measured using automated assays or ELISA. We calculated their ability to predict the need for dialysis post-transplant and correlated with the estimated time to a 50% reduction in plasma creatinine (tCr50), measured glomerular filtration rate (mGFR) and estimated GFR (eGFR).
All biomarkers measured at Day 1, except urinary L-FABP, significantly correlated with tCr50 and mGFR at Day 5. Plasma NGAL at Day 1 and a timed urine output predicted DGF (AUC = 0.91 and AUC 0.98). Nil or only weak correlations were identified between early biomarker levels and mGFR or eGFR at three or twelve months.
High plasma NGAL at Day 1 predicts DGF and is associated with initial graft function, but may not prove better than P-creatinine or a timed urine output. Early biomarker levels do not correlate with one-year graft function.
ClinicalTrials.gov NCT01395719.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ischemia reperfusion injury (IRI) is inevitable in kidney transplantation and negatively impacts graft and patient outcome. Reperfusion takes place in the recipient and most of the injury following ...ischemia and reperfusion occurs during this reperfusion phase; therefore, the intra-operative period seems an attractive window of opportunity to modulate IRI and improve short- and potentially long-term graft outcome. Commonly used volatile anesthetics such as sevoflurane and isoflurane have been shown to interfere with many of the pathophysiological processes involved in the injurious cascade of IRI. Therefore, volatile anesthetic (VA) agents might be the preferred anesthetics used during the transplantation procedure. This review highlights the molecular and cellular protective points of engagement of VA shown in in vitro studies and in vivo animal experiments, and the potential translation of these results to the clinical setting of kidney transplantation.
During ischemia−reperfusion injury (IRI), reactive oxygen species are produced that can be scavenged by free sulfhydryl groups (R-SH, free thiols). In this study, we hypothesized that R-SH levels ...decrease as a consequence of renal IRI and that R-SH levels reflect post-transplant graft function. Systemic venous, arterial, renal venous, and urinary samples were collected in donors and recipients before, during, and after transplantation. R-SH was measured colorimetrically. Systemic arterial R-SH levels in recipients increased significantly up to 30 sec after reperfusion (p < 0.001). In contrast, renal venous R-SH levels significantly decreased at 5 and 10 min compared to 30 sec after reperfusion (both p < 0.001). This resulted in a significant decrease in delta R-SH (defined as the difference between renal venous and systemic arterial R-SH levels) till 30 sec after reperfusion (p < 0.001), indicating a net decrease in R-SH levels across the transplanted kidney. Overall, these results suggest trans-renal oxidative stress as a consequence of IRI during kidney transplantation, reflected by systemic and renal changes in R-SH levels in transplant recipients.
Ischaemia-reperfusion injury in kidney transplantation leads to delayed graft function (DGF), which is associated with reduced long term graft function. Remote ischaemic conditioning (RIC) improved ...early kidney graft function in a porcine model of donation after brain death and was associated with improved long-term cardiac outcome after myocardial ischaemia. This randomised, double-blinded trial evaluated the effect of RIC on kidney graft outcome in the first year, and examined the predictive value of a new measure of initial kidney graft function, i.e. the estimated time to a 50% reduction in plasma creatinine post-transplantation (tCr50).
A total of 225 patients undergoing deceased donor kidney transplantation were randomised to RIC or a sham procedure performed prior to kidney reperfusion. Up to four repetitive cycles of five minutes of leg ischaemia and five minutes of reperfusion were given. GFR, plasma creatinine, cystatin C and neutrophil gelatinase associated lipocalin (NGAL) were measured at three and twelve months and estimated GFR was calculated using four different equations. Other secondary outcomes were identified from patient files.
RIC did not affect GFR or other outcomes when compared to the sham procedure at three or twelve months. tCr50 correlated with one year graft function (p<0.0001 for both mGFR and eGFR estimates). In contrast, DGF i.e. "need of dialysis the first week" did not correlate significantly with one year GFR.
RIC during deceased donor kidney transplantation did not improve one year outcome. However, tCr50 may be a relevant marker for studies aiming to improve graft onset.
www.ClinicalTrials.gov Identifier: NCT01395719.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this Pro-Con commentary article, we discuss whether all general anesthesia should be done using target-controlled propofol anesthesia guided by monitoring of depth of anesthesia. This is an ...ongoing debate since more than 25 years, representing a scientific, cultural as well as geographical divide in the anesthesia community. The Pro side argues that total intravenous anesthesia causes less postoperative nausea and higher patient satisfaction than anesthesia using volatile anesthetics. Target-controlled infusion (TCI) of anesthetic agents allows for better titration of intravenous anesthesia using pharmacokinetic models. Processed EEG monitors, such as bispectral index monitoring, allows for better assessing the effect of TCI anesthesia than solely assessment of clinical parameters, such as ECG or blood pressure. The combination of TCI propofol and objective depth of anesthesia monitoring allows creating a pharmacokinetic-pharmacodynamic profile for each patient. Finally, anesthesia using volatile anesthetics poses health risks for healthcare professionals and contributes to greenhouse effect. The Con side argues that for procedures accompanied with ischemia and reperfusion injury of an organ or tissue and for patients suffering from a severe inflammation' the use of volatile anesthetics might well have its advantages above propofol. In times of sudden shortage of drugs, volatile anesthetics can overcome the restriction in the operating theater or even on the intensive care unit, which is another advantage. Volatile anesthetics can be used for induction of anesthesia when IV access is impossible, end-tidal measurements of volatile anesthetic concentration allows confirmation that patients receive anesthetics. Taking environmental considerations into account, both propofol and volatile anesthetics bear certain harm to the environment, be it as waste product or as greenhouse gases. The authors therefore suggest to carefully considering advantages and disadvantages for each patient in its according environment. A well-balanced choice based on the available literature is recommended. The authors recommend careful consideration of advantages and disadvantages of each technique when tailoring an anesthetic to meet patient needs. Where appropriate, anesthesia providers are encouraged to account for unique features of anesthetic drug behavior, patient-reported and observed postoperative outcomes, and economic and environmental considerations when choosing any of the 2 described techniques.
During ischemia and reperfusion injury (IRI), mitochondria may release mitochondrial DNA (mtDNA). mtDNA can serve as a propagator of further injury but in specific settings has anti-inflammatory ...capacities as well. Therefore, the aim of this study was to study the perioperative dynamics of plasma mtDNA during living donor kidney transplantation (LDKT) and its potential as a marker of graft outcome. Fifty-six donor–recipient couples from the Volatile Anesthetic Protection of Renal Transplants-1 (VAPOR-1) trial were included. Systemic venous, systemic arterial, and renal venous samples were taken at multiple timepoints during and after LDKT. Levels of mtDNA genes changed over time and between vascular compartments. Several donor, recipient, and transplantation-related variables significantly explained the course of mtDNA genes over time. mtDNA genes predicted 1-month and 24-month estimated glomerular filtration rate (eGFR) and acute rejection episodes in the two-year follow-up period. To conclude, mtDNA is released in plasma during the process of LDKT, either from the kidney or from the whole body in response to transplantation. While circulating mtDNA levels positively and negatively predict post-transplantation outcomes, the exact mechanisms and difference between mtDNA genes are not yet understood and need further exploration.
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