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Purpose: Novel interventions for the prevention or treatment of acute kidney injury (AKI) are currently lacking. To facilitate the evaluation and adoption of new treatments, the use of the most appropriate design and endpoints for clinical trials in AKI is critical and yet there is little consensus regarding these issues. We aimed to develop recommendations on endpoints and trial design for studies of AKI prevention and treatment interventions based on existing data and expert consensus. Methods: At the 31st Acute Disease Quality Initiative (ADQI) meeting, international experts in critical care, nephrology, involving adults and pediatrics, biostatistics and people with lived experience (PWLE) were assembled. We focused on four main areas: (1) patient enrichment strategies, (2) prevention and attenuation studies, (3) treatment studies, and (4) innovative trial designs of studies other than traditional (parallel arm or cluster) randomized controlled trials. Using a modified Delphi process, recommendations and consensus statements were developed based on existing data, with > 90% agreement among panel members required for final adoption. Results: The panel developed 12 consensus statements for clinical trial endpoints, application of enrichment strategies where appropriate, and inclusion of PWLE to inform trial designs. Innovative trial designs were also considered. Conclusion: The current lack of specific therapy for prevention or treatment of AKI demands refinement of future clinical trial design. Here we report the consensus findings of the 31st ADQI group meeting which has attempted to address these issues including the use of predictive and prognostic enrichment strategies to enable appropriate patient selection. [ABSTRACT FROM AUTHOR]

Angiotensin II (ANGII) is a peptide that increases blood pressure and is part of the renin-angiotensin-aldosterone system (RAAS). It has recently been approved as a vasopressor drug for the treatment of vasodilatory hypotension and shock in the ICU. The ATHOS-3 trial demonstrated that ANGII was effective in increasing mean arterial pressure and achieving target blood pressure in patients with catecholamine-refractory vasodilatory shock. Subgroup analyses showed that ANGII was particularly beneficial for patients on renal replacement therapy and those with elevated plasma renin concentration. Further studies are needed to determine the optimal timing, patient selection, and duration of ANGII therapy, as well as its use in combination with other agents. [Extracted from the article]

Acute kidney injury (AKI) is a common clinical condition with various causes and is associated with increased mortality. Despite advances in supportive care, AKI increases not only the risk of premature death compared with the general population but also the risk of developing chronic kidney disease and progressing towards kidney failure. Currently, no specific therapy exists for preventing or treating AKI other than mitigating further injury and supportive care. To address this unmet need, novel therapeutic interventions targeting the underlying pathophysiology must be developed. New and well-designed clinical trials with appropriate end points must be subsequently designed and implemented to test the efficacy of such new interventions. Herein, we discuss predictive and prognostic enrichment strategies for patient selection, as well as primary and secondary end points that can be used in different clinical trial designs (specifically, prevention and treatment trials) to evaluate novel interventions and improve the outcomes of patients at a high risk of AKI or with established AKI. Several factors complicate the identification of effective interventions that can improve the outcomes of patients with acute kidney injury (AKI). Here, the authors discuss key design considerations for clinical trials in hospitalized patients with AKI, including the selection of adequate patient cohorts and study end points. Key points: Acute kidney injury (AKI) is a very heterogeneous syndrome; therefore, enrichment strategies are required to reduce heterogeneity within the study patient cohort and to reduce sample size. Several factors, including risk scores, biomarkers and clinical features, can be used for prognostic and predictive enrichment. Careful selection of end points is crucial for any trial. Different end points are required for phase II and phase III trials, and for prevention, attenuation and treatment trials. The occurrence of AKI is a key end point in prevention or attenuation trials and is mainly assessed based on current AKI definitions (based on serum creatinine and urine output) but biomarkers can be used as surrogate end points in phase II trials. Major adverse kidney events cannot be used in prevention trials, but different components in this composite end point should always be reported when used in treatment trials. The trajectory of AKI is an important outcome in intervention trials, because clinical measures or drugs might influence the course of AKI and subsequently influence the mortality rate. [ABSTRACT FROM AUTHOR]

Sepsis is a host's deleterious response to infection, which could lead to life-threatening organ dysfunction. Sepsis-associated acute kidney injury (SA-AKI) is the most frequent organ dysfunction and is associated with increased morbidity and mortality. Sepsis contributes to ≈50% of all AKI in critically ill adult patients. A growing body of evidence has unveiled key aspects of the clinical risk factors, pathobiology, response to treatment and elements of renal recovery that have advanced our ability to detect, prevent and treat SA-AKI. Despite these advancements, SA-AKI remains a critical clinical condition and a major health burden, and further studies are needed to diminish the short and long-term consequences of SA-AKI. We review the current treatment standards and discuss novel developments in the pathophysiology, diagnosis, outcome prediction and management of SA-AKI. [ABSTRACT FROM AUTHOR]

Purpose: The incidence, patient features, risk factors and outcomes of surgery-associated postoperative acute kidney injury (PO-AKI) across different countries and health care systems is unclear. Methods: We conducted an international prospective, observational, multi-center study in 30 countries in patients undergoing major surgery (> 2-h duration and postoperative intensive care unit (ICU) or high dependency unit admission). The primary endpoint was the occurrence of PO-AKI within 72 h of surgery defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary endpoints included PO-AKI severity and duration, use of renal replacement therapy (RRT), mortality, and ICU and hospital length of stay. Results: We studied 10,568 patients and 1945 (18.4%) developed PO-AKI (1236 (63.5%) KDIGO stage 1500 (25.7%) KDIGO stage 2209 (10.7%) KDIGO stage 3). In 33.8% PO-AKI was persistent, and 170/1945 (8.7%) of patients with PO-AKI received RRT in the ICU. Patients with PO-AKI had greater ICU (6.3% vs. 0.7%) and hospital (8.6% vs. 1.4%) mortality, and longer ICU (median 2 (Q1-Q3, 1–3) days vs. 3 (Q1-Q3, 1–6) days) and hospital length of stay (median 14 (Q1-Q3, 9–24) days vs. 10 (Q1-Q3, 7–17) days). Risk factors for PO-AKI included older age, comorbidities (hypertension, diabetes, chronic kidney disease), type, duration and urgency of surgery as well as intraoperative vasopressors, and aminoglycosides administration. Conclusion: In a comprehensive multinational study, approximately one in five patients develop PO-AKI after major surgery. Increasing severity of PO-AKI is associated with a progressive increase in adverse outcomes. Our findings indicate that PO-AKI represents a significant burden for health care worldwide. [ABSTRACT FROM AUTHOR]

Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients and is strongly associated with adverse outcomes, including an increased risk of chronic kidney disease, cardiovascular events and death. The pathophysiology of SA-AKI remains elusive, although microcirculatory dysfunction, cellular metabolic reprogramming and dysregulated inflammatory responses have been implicated in preclinical studies. SA-AKI is best defined as the occurrence of AKI within 7 days of sepsis onset (diagnosed according to Kidney Disease Improving Global Outcome criteria and Sepsis 3 criteria, respectively). Improving outcomes in SA-AKI is challenging, as patients can present with either clinical or subclinical AKI. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Accordingly, the discovery of biomarkers associated with AKI that can aid in early diagnosis is an area of intensive investigation. Additionally, high-quality evidence on best-practice care of patients with AKI, sepsis and SA-AKI has continued to accrue. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches. Here we provide graded recommendations for managing SA-AKI and highlight priorities for future research. Sepsis-associated acute kidney injury (SA-AKI) is linked with poor outcomes in critically ill patients. This Consensus Statement from the Acute Disease Quality Initiative discusses the definition, epidemiology and pathophysiology of SA-AKI, fluid, resuscitation and extracorporeal therapies, and the role of biomarkers in risk stratification and diagnosis. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most common aging-associated neurodegenerative disease; nevertheless, the etiology and progression of the disease is still incompletely understood. We have previously shown that the microbially-derived metabolite trimethylamine N-oxide (TMAO) is elevated in the cerebrospinal fluid (CSF) of individuals with cognitive impairment due to AD and positively correlates with increases in CSF biomarkers for tangle, plaque, and neuronal pathology.Objective: We assessed the direct impact of TMAO on AD progression.Methods: To do so, transgenic 5XFAD mice were supplemented with TMAO for 12 weeks. Neurite density was assessed through quantitative brain microstructure imaging with neurite orientation dispersion and density imaging magnetic resonance imaging (MRI). Label-free, quantitative proteomics was performed on cortex lysates from TMAO-treated and untreated animals. Amyloid-β plaques, astrocytes, and microglia were assessed by fluorescent immunohistochemistry and synaptic protein expression was quantified via western blot.Results: Oral TMAO administration resulted in significantly reduced neurite density in several regions of the brain. Amyloid-β plaque mean intensity was reduced, while plaque count and size remained unaltered. Proteomics analysis revealed that TMAO treatment impacted the expression of 30 proteins (1.5-fold cut-off) in 5XFAD mice, including proteins known to influence neuronal health and amyloid-β precursor protein processing. TMAO treatment did not alter astrocyte and microglial response nor cortical synaptic protein expression.Conclusion: These data suggest that elevated plasma TMAO impacts AD pathology via reductions in neurite density. [ABSTRACT FROM AUTHOR]

Background: Acutely occurring organ damage significantly contributes to morbidity and mortality in the perioperative context. Objective: This article highlights new clinical perspectives on how perioperative organ damage can be prevented and ameliorated by influencing the high mobility group box 1 protein (HMGB1) signaling. Material and methods: A MEDLINE search was performed in the fields of clinical and basic research. The presentation of basic mechanisms of perioperative organ damage and the discussion of the importance of HMGB1 in prevention and treatment by pharmaceutical and nonpharmaceutical interventions are the focus of the review. Results: The HMGB1 is a central element in the pathogenesis of septic and aseptic inflammation-induced organ damage. Remote ischemic preconditioning (RIPC) and dexmedetomidine are highly effective approaches to mitigate or prevent organ damage. Conclusion: The RIPC and dexmedetomidine offer protective properties in ischemia-reperfusion injury as well as in inflammation-related organ damage, which are mediated by HMGB1, among others. This effectively protects the kidneys, heart, lungs, liver and brain. The application of these concepts should be considered in routine clinical practice. [ABSTRACT FROM AUTHOR]

Indeed, systemic concentrations of pro-inflammatory cytokines in patients with severe COVID-19 are not as high as has been reported in patients with other causes of acute respiratory distress syndrome. On April 10, 2020, the U.S. Food and Drug Administration granted Emergency Use Authorization for CytoSorb use in critically ill COVID-19 patients with confirmed or imminent respiratory failure. Keywords: COVID-19; cytokine adsorber; organ failure; vasoplegic shock EN COVID-19 cytokine adsorber organ failure vasoplegic shock 1026 1029 4 05/27/22 20220601 NES 220601 "However beautiful the strategy, you should occasionally look at the results." is a famous saying by Sir Winston Churchill. In a prospective, randomized, open-label study, Supady et al ([11]) investigated 34 COVID-19 patients with ECMO therapy and showed that the median IL-6 drop over 72 hours occurred regardless of the use of CytoSorb ([11]). [Extracted from the article]

Auchet et al. et al. reported 90 days survival of 40% in patients receiving vasopressor > 1 µg/kg/min underlining fair survival on very high doses of vasopressors [[17]]. There is no maximal dose of vasopressors Not surprisingly, high doses of vasopressors have been associated with a higher risk of death given the higher severity of illness of these patients. Vasopressors induce an endogenous fluid recruitment and may limit positive fluid balance Vasopressors increase blood pressure through the increase of systemic vascular resistance. [Extracted from the article]

We read with interest the paper by White et al. [[1]] reporting that up to 18% of patients admitted to the intensive care unit (ICU) met sepsis-associated acute kidney injury (SA-AKI) criteria. This is three times the occurrence of sepsis reported by some of the same authors in a prior publications, suggesting an occurrence of sepsis (then referred to as severe sepsis) in Australia of 9.7% [[2]]. [Extracted from the article]

Accessory and anomalous muscles are common in humans, although their unique morphologic characteristics can make accurate identification difficult. In this case report, we attempt to identify an anomalous accessory muscle of the posterior compartment of the leg [Compartimentum posterius cruris] detected during cadaveric dissection and discuss its clinical significance. The muscle was found on the right lower limb of an 81-year-old female cadaver and extended from the distal femur to attach to the gastrocnemius muscle at the point where the medial and lateral heads fuse. At its origin, the muscle was found lateral to the popliteal vessels and crossed posterior to these vessels and tibial nerve. It displayed characteristics similar to both an accessory plantaris muscle and gastrocnemius tertius, thus making its ultimate identification difficult. Though the muscle displayed a morphologically similar appearance to the plantaris, we suggest that its common insertion with the gastrocnemius best identifies it as a gastrocnemius tertius. In addition, due to its relationship with the popliteal neurovasculature, it is possible that this muscle could have resulted in neurovascular entrapment although it is unknown whether or not this cadaver exhibited symptoms. [ABSTRACT FROM AUTHOR]

Craniotomy or decompressive craniectomy are among the therapeutic options to prevent or treat secondary damage after severe brain injury. The choice of procedure depends, among other things, on the type and severity of the initial injury. It remains controversial whether both procedures influence the neurological outcome differently. Thus, estimating the risk of brain herniation and death and consequently potential organ donation remains difficult. All patients at the University Hospital Münster for whom an isolated craniotomy or decompressive craniectomy was performed as a treatment after severe brain injury between 2013 and 2022 were retrospectively included. Proportion of survivors and deceased were evaluated. Deceased were further analyzed regarding anticoagulants, comorbidities, type of brain injury, potential and utilized donation after brain death. 595 patients were identified, 296 patients survived, and 299 deceased. Proportion of decompressive craniectomy was higher than craniotomy in survivors (89% vs. 11%, p < 0.001). Brain death was diagnosed in 12 deceased and 10 donations were utilized. Utilized donations were comparable after both procedures (5% vs. 2%, p = 0.194). Preserved brain stem reflexes as a reason against donation did not differ between decompressive craniectomy or craniotomy (32% vs. 29%, p = 0.470). Patients with severe brain injury were more likely to survive after decompressive craniectomy than craniotomy. Among the deceased, potential and utilized donations did not differ between both procedures. This suggests that brain death can occur independent of the previous neurosurgical procedure and that organ donation should always be considered in end-of-life decisions for patients with a fatal prognosis. [ABSTRACT FROM AUTHOR]

Importance: Although current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses.Objective: To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality.Design, Setting, and Participants: A parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled.Interventions: Patients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy.Main Outcomes and Measures: Coprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections.Results: Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P < .001). Ninety-day all-cause mortality occurred in 150 of 300 patients vs 156 of 296 patients (Kaplan-Meier estimator percentages, 51.2% vs 53.6%; unadjusted difference, -2.4% [95% CI, -10.5% to 5.8%]; unadjusted hazard ratio, 0.91 [95% CI, 0.72 to 1.13]; unadjusted P = .38; adjusted difference, -6.1% [95% CI, -12.6% to 0.4%]; primary adjusted hazard ratio, 0.79 [95% CI, 0.63 to 1.004]; primary adjusted P = .054). Of 38 prespecified secondary end points, 34 showed no significant difference. Compared with the systemic heparin group, the regional citrate group had significantly fewer bleeding complications (15/300 [5.1%] vs 49/296 [16.9%]; difference, -11.8% [95% CI, -16.8% to -6.8%]; P < .001) and significantly more new infections (204/300 [68.0%] vs 164/296 [55.4%]; difference, 12.6% [95% CI, 4.9% to 20.3%]; P = .002).Conclusions and Relevance: Among critically ill patients with acute kidney injury receiving continuous kidney replacement therapy, anticoagulation with regional citrate, compared with systemic heparin anticoagulation, resulted in significantly longer filter life span. The trial was terminated early and was therefore underpowered to reach conclusions about the effect of anticoagulation strategy on mortality.Trial Registration: ClinicalTrials.gov Identifier: NCT02669589. [ABSTRACT FROM AUTHOR]

Schema therapy has shown good effectiveness in individual and group settings. Experiential techniques, in particular, seem to contribute to those effects. In a randomized controlled trial with 12 couples, we compared the effects of couple imagery rescripting exercises and a cognitive intervention based on the schema therapy model in a crossover design. We measured the couples' sense of closeness, using daily VAS-scales, and on mood (BDI-II). Imagery rescripting showed significantly stronger effects on the felt closeness and mood of both partners than schema model-based cognitive therapy techniques. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) remains a common clinical syndrome associated with increased morbidity and mortality. In the last several years there have been several advances in the identification of patients at increased risk for AKI through the use of traditional and newer functional and damage biomarkers of AKI. This article will specifically focus on the impact of biomarkers of AKI on individual patient care, focusing predominantly on the markers with the most expansive breadth of study in patients and reported literature evidence. Several studies have demonstrated that close monitoring of widely available biomarkers such as serum creatinine and urine output is strongly associated with improved patient outcomes. An integrated approach to these biomarkers used in context with patient risk factors (identifiable using electronic health record monitoring) and with tests of renal reserve may guide implementation and targeting of care bundles to optimize patient care. Besides traditional functional markers, biochemical injury biomarkers have been increasingly utilized in clinical trials both as a measure of kidney injury as well as a trigger to initiate other treatment options (e.g. care bundles and novel therapies). As the novel measures are becoming globally available, the clinical implementation of hospital-based real-time biomarker measurements involves a multidisciplinary approach. This literature review discusses the data evidence supporting both the strengths and limitations in the clinical implementation of biomarkers based on the authors' collective clinical experiences and opinions. [ABSTRACT FROM AUTHOR]

Platelets have long been known for their role in hemostasis. In this, platelet adhesion and activation leads to the formation of a firm thrombus and thus the sealing of a damaged blood vessel. More recently, inflammatory modes of function have been attributed to these non-nuclei-containing cellular fragments. Interaction with leukocytes, secretion of proinflammatory mediators, and migratory behavior are some of the recent discoveries. Nonetheless, platelets also have anti-inflammatory potential by regulating macrophage functions, regulatory T cells, and secretion of proresolving mediators. This review summarizes current knowledge of platelet functions with a special focus on inflammation and resolution of inflammation. [ABSTRACT FROM AUTHOR]

The article discusses the use of 20% albumin for fluid bolus therapy after cardiac surgery. The study, called the HAS FLAIR-II RCT, aimed to evaluate the effect of albumin on the duration of vasopressor therapy compared to crystalloid. The results showed that albumin did not have a significant effect on vasopressor duration or mortality, but it was associated with a reduced fluid balance. The study also explored the potential benefits of albumin for hypoalbuminemic patients and its role in reducing the incidence of acute kidney injury. The article concludes by suggesting that further research is needed to provide definitive evidence on the topic. [Extracted from the article]

Prevention of cardiac surgery-associated acute kidney injury by implementing the KDIGO guidelines in high-risk patients identified by biomarkers: the PrevAKI-multicenter randomized controlled trial. The PrevAKI-1 trial used a personalised approach using novel renal biomarkers (tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein-7) to identify cardiac surgical patients at risk of AKI. Bundle effectiveness was not restricted to cardiac surgical patients but could also be demonstrated in patients undergoing abdominal surgery, suggesting that the biomarker-guided implementation of the KDIGO bundle is effective in surgical patients [[2], [4]]. [Extracted from the article]

LINKED CONTENT: This article is linked to Wong et al papers. To view these articles, visit https://doi.org/10.1111/apt.17195 and https://doi.org/10.1111/apt.17323 [ABSTRACT FROM AUTHOR]

Background: Cardiac surgery is associated with a high risk of postoperative acute kidney injury (AKI) and subsequent loss of kidney function. We explored the clinical utility of urinary dickkopf-3 (DKK3), a renal tubular stress marker, for preoperative identification of patients at risk for AKI and subsequent kidney function loss.Methods: This observational cohort study included patients who had cardiac surgery in a derivation cohort and those who had cardiac surgery in a validation cohort (RenalRIP trial). The study comprised consecutive patients who had elective cardiac surgery at the Saarland University Medical Centre (Homburg, Germany; derivation cohort) and those undergoing elective cardiac surgery (selected on the basis of a Cleveland Clinical Foundation score of 6 or higher) who were enrolled in the prospective RenalRIP multicentre trial (validation cohort) and who were randomly assigned to remote ischaemic preconditioning or a sham procedure. The association between the ratio of preoperative urinary concentrations of DKK3 to creatinine (DKK3:creatinine) and postoperative AKI, defined according to the Kidney Disease Improving Global Outcomes criteria, and subsequent kidney function loss, as determined by estimated glomerular filtration rate, was assessed.Findings: In the 733 patient in the derivation cohort, urinary concentrations of DKK3 to creatinine that were higher than 471 pg/mg were associated with significantly increased risk for AKI (odds ratio [OR] 1·65, 95% CI 1·10-2·47, p=0·015), independent of baseline kidney function. Compared with clinical and other laboratory measurements, urinary concentrations of DKK3:creatinine significantly improved AKI prediction (net reclassification improvement 0·32, 95% CI 0·23-0·42, p<0·0001). High urinary DKK3:creatinine concentrations were independently associated with significantly lower kidney function at hospital discharge and after a median follow-up of 820 days (IQR 733-910). In the RenalRIP trial, preoperative urinary DKK3:creatinine concentrations higher than 471 pg/mg were associated with a significantly higher risk for AKI (OR 1·94, 95% CI 1·08-3·47, p=0·026), persistent renal dysfunction (OR 6·67, 1·67-26·61, p=0·0072), and dialysis dependency (OR 13·57, 1·50-122·77, p=0·020) after 90 days compared with DKK3:creatinine concentrations of 471 pg/mg or less. Urinary DKK3:creatinine concentrations higher than 471 pg/mg were associated with significantly higher risk for AKI (OR 2·79, 95% CI 1·45-5·37) and persistent renal dysfunction (OR 3·82, 1·32-11·05) only in patients having a sham procedure, but not remote ischaemic preconditioning (AKI OR 1·35, 0·76-2·39 and persistent renal dysfunction OR 1·05, 0·12-9·45).Interpretation: Preoperative urinary DKK3 is an independent predictor for postoperative AKI and for subsequent loss of kidney function. Urinary DKK3 might aid in the identification of patients in whom preventive treatment strategies are effective.Funding: No study funding. [ABSTRACT FROM AUTHOR]

Background: The incidence of acute kidney injury (AKI) has increased over the last decades. Renal replacement therapy (RRT) is increasingly being used. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines define AKI by serum creatinine (SCr) elevation and decrease in urinary output (UO) and suggest prevention strategies and recommendations on the management of RRT. Treatment options are limited and RRT remains the gold standard as supportive treatment but implies a substantial escalation of treatment. With respect to the indications and management of RRT, there are only a few evidence-based recommendations.Objective: This review summarizes the clinical relevance of AKI and presents the most important aspects on the indications and implementation of RRT.Material and Methods: The available evidence is summarized based on the current literature.Results: Implementation of the KDIGO bundles to prevent AKI in high-risk patients reduces the incidence of AKI. In the absence of absolute indications, the evidence-based recommendations on when to initiate RRT are limited and controversial. Intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) procedures can be considered as complementary therapeutic strategies. The CRRT is recommended in hemodynamically unstable patients. Regional citrate anticoagulation is the recommended anticoagulation in CRRT. The optimal effluent dose is effectively 20-25 ml/kg body weight and hour. Spontaneous diuresis is a best predictor of successful cessation of RRT.Conclusion: Risk identification and prevention of AKI are essential. In the absence of absolute indications, initiation and accomplishment of RRT should be patient-adapted and carried out in the clinical context. Newly developed biomarkers could be helpful in the future for a better estimation of the prognosis and for a more precise definition of therapeutic strategies of RRT. [ABSTRACT FROM AUTHOR]

Background: Adults with congenital heart disease (CHD) represent an increasing proportion of patients undergoing non-cardiac surgery.Objective: To identify the most important parameters for management of anesthesia.Material and Methods: Evaluation and discussion of the current original research and guideline recommendations.Results: There are approximately 300,000 patients with CHD living in Germany. The preoperative evaluation is an important influencing factor affecting perioperative morbidity and mortality. Echocardiography is the key instrument for identifying cardiac conditions predisposing to adverse events. The subdivision of CHD into lesions with left-to-right shunt, obstructive lesions and complex congenital heart diseases facilitates the classification of the pathophysiology.Conclusion: Decisive for the perioperative outcome of patients with CHD are the identification of high-risk patients, understanding of the individual situation with respect to the underlying pathophysiology and the intraoperative maintenance of cardiac output. [ABSTRACT FROM AUTHOR]

We advocate that after more than 170,000 human CytoSorb treatments performed in the last decade, it is the highest time for compelling evidence from RCTs showing improvement of clinically relevant endpoints before using the CytoSorb in ever expanding indications. We appreciate the letter by Kogelmann ([1]) raising concerns that our editorial comment concentrated only on a few negative studies from various application. Kogelmann ([1]) argued that some studies investigated the CytoSorb in patient populations who had low cytokine levels and that the device only works in patients who have high cytokine levels. [Extracted from the article]

The role of the renin-angiotensin-aldosterone axis in vasoplegia after cardiac surgery remains unclear. We tested the hypothesis that, compared with norepinephrine, infusion of angiotensin II titrated to achieve similar mean arterial pressure (MAP) would suppress plasma renin concentration (PRC) while maintaining aldosterone levels. In a double-blind, randomised controlled trial, subjects received either an infusion of angiotensin II or norepinephrine to maintain MAP 70–80 mm Hg from induction of anaesthesia. We compared PRC, aldosterone, dipeptidyl peptidase-3, and angiotensin-converting enzyme 2 activity between treatment groups, before surgery, on ICU admission, and 24 h after surgery. In 60 patients (11.7% female; mean age 68 yr [11 yr]), norepinephrine increased median PRC at ICU admission (median difference [MD] 46 [inter-quartile range, IQR, 3–88] μU ml−1; P <0.001) but angiotensin II did not (MD −3 [IQR −62 to 35] μU ml−1; P =0.36). Aldosterone levels increased with both. The aldosterone:PRC ratio did not change with norepinephrine (MD −0.01 [IQR −0.14 to 0.03] μU ml−1 per ng dl−1, P =0.76) but increased with angiotensin II (MD 0.05 [IQR 0.004–0.26] μU ml−1 per ng dl−1, P <0.001). The upper quartile of PRC before surgery was associated with higher vasopressor requirements when norepinephrine was used to maintain MAP, but not angiotensin II. Dipeptidyl peptidase-3 levels and angiotensin-converting enzyme 2 activities were similar at all time points. Angiotensin II suppressed renin release while maintaining aldosterone levels compared with norepinephrine. Higher plasma renin concentration before surgery was associated with greater vasopressor requirement for norepinephrine, but not angiotensin II. Australian and New Zealand Clinical Trials Registry—ACTRN12621000195853 23/02/2021. [ABSTRACT FROM AUTHOR]

Background: In a multicenter, randomized trial, the authors enrolled patients at high-risk for acute kidney injury as identified by a Cleveland Clinic Foundation score of 6 or more. The authors enrolled 240 patients at four hospitals and randomized them to remote ischemic preconditioning or control. The authors found that remote ischemic preconditioning reduced acute kidney injury in high-risk patients undergoing cardiac surgery. The authors now report on the effects of remote ischemic preconditioning on 90-day outcomes.Methods: In this follow-up study of the RenalRIP trial, the authors examined the effect of remote ischemic preconditioning on the composite endpoint major adverse kidney events consisting of mortality, need for renal replacement therapy, and persistent renal dysfunction at 90 days. Secondary outcomes were persistent renal dysfunction and dialysis dependence in patients with acute kidney injury.Results: Remote ischemic preconditioning significantly reduced the occurrence of major adverse kidney events at 90 days (17 of 120 [14.2%]) versus control (30 of 120 [25.0%]; absolute risk reduction, 10.8%; 95% CI, 0.9 to 20.8%; P = 0.034). In those patients who developed acute kidney injury after cardiac surgery, 2 of 38 subjects in the remote ischemic preconditioning group (5.3%) and 13 of 56 subjects in the control group (23.2%) failed to recover renal function at 90 days (absolute risk reduction, 17.9%; 95% CI, 4.8 to 31.1%; P = 0.020). Acute kidney injury biomarkers were also increased in patients reaching the major adverse kidney event endpoint compared to patients who did not.Conclusions: Remote ischemic preconditioning significantly reduced the 3-month incidence of a composite endpoint major adverse kidney events consisting of mortality, need for renal replacement therapy, and persistent renal dysfunction in high-risk patients undergoing cardiac surgery. Furthermore, remote ischemic preconditioning enhanced renal recovery in patients with acute kidney injury. [ABSTRACT FROM AUTHOR]

A Novel Approach for the Targeted Inhibition of Platelet Activation - Separating the Good From the Bad* But more importantly, ADP by itself is a rather weak platelet agonist, but it might act synergistically with other platelet agonists (e.g., thrombin or TxA SB 2 sb ) to booster the response of platelets. They used the nucleoside triphosphate hydrolase (NTPase) CD39 to convert the platelet agonist ADP into inactive adenosine monophosphate by hydrolysis, thus limit platelet activation. Thus, the hydrolytic activity of CD39 enriched in the proximity of activated platelets, as only these platelets possess the platelet integrin glycoprotein IIb/IIIa in its activated state. [Extracted from the article]

Background: Continuous positive airway pressure is a noninvasive respiratory support technique that may prevent pulmonary complications following cardiac surgery. This study was conducted to determine the efficacy of prophylactic nasal continuous positive airway pressure (nCPAP) compared with standard treatment. The primary end points were pulmonary adverse effects defined as hypoxemia (Pao(2)/fraction of inspired oxygen [Fio(2)] <100), pneumonia, and reintubation. The secondary end point was the readmission rate to the ICU or intermediate care unit (IMCU).Methods: We prospectively randomized 500 patients scheduled for elective cardiac surgery. Following extubation either in the operating room (early) or in the ICU (late), patients were allocated to standard treatment (control) including 10 min of intermittent nCPAP at 10 cm H(2)O every 4 h or prophylactic nCPAP (study) at an airway pressure of 10 cm H(2)O for at least 6 h.Results: Prophylactic nCPAP significantly improved arterial oxygenation (Pao(2)/Fio(2)) without altering heart rate and mean arterial BP. Pulmonary complications including hypoxemia (defined as Pao(2)/Fio(2) <100), pneumonia, and reintubation rate were reduced in study patients compared to controls (12 of 232 patients vs 25 of 236 patients, respectively; p = 0.03). The readmission rate to the ICU or IMCU was significantly lower in nCPAP-treated patients (7 of 232 patients vs 14 of 236 patients, respectively; p = 0.03).Conclusions: The long-term administration of prophylactic nCPAP following cardiac surgery improved arterial oxygenation, reduced the incidence of pulmonary complications including pneumonia and reintubation rate, and reduced readmission rate to the ICU or IMCU. Thus noninvasive respiratory support with nCPAP is a useful tool to reduce pulmonary morbidity following elective cardiac surgery. [ABSTRACT FROM AUTHOR]

Objective: Acute renal failure remains a major challenge in critical care medicine. Both neutrophils and chemokines have been proposed as key components in the development of acute renal failure. Although the Duffy antigen receptor for chemokines (DARC) is present in several tissues and a highly specific ligand for various chemokines, its exact role in vivo remains unclear.Design: Prospective, controlled experimental study.Setting: University-based research laboratory.Subjects: C57BL/6 wild-type and DARC gene-deficient mice (DARC-/-).Interventions: To unravel the functional relevance of DARC in vivo, we compared wild-type and DARC-/- using neutrophil-dependent models of acute renal failure, induced by either local (renal ischemia-reperfusion) or systemic (endotoxemia, lipopolysaccharide) injury.Measurements and Main Results: Plasma creatinine and blood urea nitrogen concentrations served as indicators of renal function or dysfunction. Enzyme-linked immunosorbent assays were used to measure tissue and plasma chemokine concentrations. We also performed immunostaining to localize chemokine expression and flow cytometry to evaluate neutrophil recruitment into the kidney. Following renal injury, wild-type mice developed moderate renal ischemia-reperfusion(lipopolysaccharide, 300% increase in plasma creatinine concentrations) to severe acute renal failure (renal ischemia-reperfusion, 40% mortality) as well as extensive renal neutrophil recruitment. DARC-/- mice exhibited no renal dysfunction (renal ischemia-reperfusion) or only very mild renal dysfunction (lipopolysaccharide, 20% increase in serum creatinine concentrations). DARC-/- mice showed no postischemic neutrophil infiltration. Although DARC-/- and wild-type mice exhibited similar global renal neutrophil-recruitment during endotoxemia, DARC-/- mice showed significantly impaired neutrophil extravasation. Total renal concentrations of the chemokine macrophage inflammatory protein 2, which has been shown to bind to DARC and to be crucial in postischemic acute renal failure, were either identical (lipopolysaccharide) or only moderately different (renal ischemia-reperfusion) between wild-type and DARC-/- mice. Immunostaining revealed an absence of macrophage inflammatory protein-2 in renal endothelial cells of DARC-/- mice.Conclusions: We suggest that DARC predominantly exerts its effects by controlling spatial chemokine distribution, which in turn regulates neutrophil recruitment and subsequent acute renal failure. [ABSTRACT FROM AUTHOR]

IMPORTANCE: Optimal timing of initiation of renal replacement therapy (RRT) for severe acute kidney injury (AKI) but without life-threatening indications is still unknown. OBJECTIVE: To determine whether early initiation of RRT in patients who are critically ill with AKI reduces 90-day all-cause mortality. DESIGN, SETTING, AND PARTICIPANTS: Single-center randomized clinical trial of 231 critically ill patients with AKI Kidney Disease: Improving Global Outcomes (KDIGO) stage 2 (≥2 times baseline or urinary output <0.5 mL/kg/h for ≥12 hours) and plasma neutrophil gelatinase-associated lipocalin level higher than 150 ng/mL enrolled between August 2013 and June 2015 from a university hospital in Germany. INTERVENTIONS: Early (within 8 hours of diagnosis of KDIGO stage 2; n=112) or delayed (within 12 hours of stage 3 AKI or no initiation; n=119) initiation of RRT. MAIN OUTCOMES AND MEASURES: The primary end point was mortality at 90 days after randomization. Secondary end points included 28- and 60-day mortality, clinical evidence of organ dysfunction, recovery of renal function, requirement of RRT after day 90, duration of renal support, and intensive care unit (ICU) and hospital length of stay. RESULTS: Among 231 patients (mean age, 67 years; men, 146 [63.2%]), all patients in the early group (n=112) and 108 of 119 patients (90.8%) in the delayed group received RRT. All patients completed follow-up at 90 days. Median time (Q1, Q3) from meeting full eligibility criteria to RRT initiation was significantly shorter in the early group (6.0 hours [Q1, Q3: 4.0, 7.0]) than in the delayed group (25.5 h [Q1, Q3: 18.8, 40.3]; difference, -21.0 [95% CI, -24.0 to -18.0]; P<.001). Early initiation of RRT significantly reduced 90-day mortality (44 of 112 patients [39.3%]) compared with delayed initiation of RRT (65 of 119 patients [54.7%]; hazard ratio [HR], 0.66 [95% CI, 0.45 to 0.97]; difference, -15.4% [95% CI, -28.1% to -2.6%]; P=.03). More patients in the early group recovered renal function by day 90 (60 of 112 patients [53.6%] in the early group vs 46 of 119 patients [38.7%] in the delayed group; odds ratio [OR], 0.55 [95% CI, 0.32 to 0. 93]; difference, 14.9% [95% CI, 2.2% to 27.6%]; P=.02). Duration of RRT and length of hospital stay were significantly shorter in the early group than in the delayed group (RRT: 9 days [Q1, Q3: 4, 44] in the early group vs 25 days [Q1, Q3: 7, >90] in the delayed group; P=.04; HR, 0.69 [95% CI, 0.48 to 1.00]; difference, -18 days [95% CI, -41 to 4]; hospital stay: 51 days [Q1, Q3: 31, 74] in the early group vs 82 days [Q1, Q3: 67, >90] in the delayed group; P<.001; HR, 0.34 [95% CI, 0.22 to 0.52]; difference, -37 days [95% CI, -∞ to -19.5]), but there was no significant effect on requirement of RRT after day 90, organ dysfunction, and length of ICU stay. CONCLUSIONS AND RELEVANCE: Among critically ill patients with AKI, early RRT compared with delayed initiation of RRT reduced mortality over the first 90 days. Further multicenter trials of this intervention are warranted. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury remains a common complication in critically ill patients and despite multiple trials and observational studies, the optimal timing for initiation of renal replacement therapy is still unclear. The early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury (ELAIN) study is a randomized, single-center, prospective, two-arm, parallel group trial to reduce mortality in patients with severe acute kidney injury. We describe the study design and discuss aspects of the need for a trial in this patient cohort.Methods/design: Our plan is to randomize critically ill patients with acute kidney injury to 'early' or 'late' initiation of renal replacement therapy according to stage 2 and 3 of the KDIGO classification using a specific trial protocol. We plan to guide data collection and analysis using pre-existing definitions and testing. The primary endpoint is overall survival in a 90-day follow-up period. Secondary endpoints include 28-day, 60-day, 90-day and 1-year all-cause mortality, recovery of renal function, ICU and hospital length-of-stay. The primary analysis will be an intention-to-treat analysis; secondary analyses include treated analyses. We will also specify rules for handling data and determining outcome.Discussion: Several challenges for study design and execution can be seen in our trial, and it should generate results that will inform and influence the practice of renal replacement therapy in critically ill patients with acute kidney injury.Trial Registration: German Clinical Trials Register: DRKS00004367 ( www.germanctr.de ); 28 May 2013. [ABSTRACT FROM AUTHOR]

Objective: Acute kidney injury is a common complication in critically ill patients and is associated with increased morbidity and mortality. Sepsis, major surgery, and nephrotoxic drugs are the most common causes of acute kidney injury. There is currently no effective strategy available to prevent or treat acute kidney injury. Therefore, novel treatment regimens are required to decrease acute kidney injury prevalence and to improve clinical outcomes. Remote ischemic preconditioning, triggered by brief episodes of ischemia and reperfusion applied in distant tissues or organs before the injury of the target organ, attempts to invoke adaptive responses that protect against acute kidney injury. We sought to evaluate the clinical evidence for remote ischemic preconditioning as a potential strategy to protect the kidney and to review the underlying mechanisms in light of recent studies.Data Sources: We searched PubMed for studies reporting the effect of remote ischemic preconditioning on kidney function in surgical patients (search terms: "remote ischemic preconditioning," "kidney function," and "surgery"). We also reviewed bibliographies of relevant articles to identify additional citations.Study Selection: Published studies, consisting of randomized controlled trials, are reviewed.Data Extraction: The authors used consensus to summarize the evidence behind the use of remote ischemic preconditioning.Data Synthesis: In addition, the authors suggest patient populations and clinical scenarios in which remote ischemic preconditioning might be best applied.Conclusions: Several experimental and clinical studies have shown tissue-protective effects of remote ischemic preconditioning in various target organs, including the kidneys. Remote ischemic preconditioning may offer a novel, noninvasive, and inexpensive treatment strategy for decreasing acute kidney injury prevalence in high-risk patients. Although many new studies have further advanced our knowledge in this area, the appropriate intensity of remote ischemic preconditioning, its mechanisms of action, and the role of biomarkers for patient selection and monitoring are still unknown. [ABSTRACT FROM AUTHOR]

Platelets have a longstanding recognition as an essential cellular component of the coagulation system. However, substantial research over the last decade has added another important aspect to platelet function in that they are also an integral part of the innateimmunesystem. Complex organisms are facing a constant threatof infections by invading pathogens, and they have developed a sophisticated and elegant measure to combat this threat, namely the immune system. Leucocyte recruitment to sites of infections is an essential step at the forefront of theimmuneresponse. Platelets have been shownto be involved in several steps of this process and they are an integrated connecting element among haemostasis, host defence, and additional immunological functions (e.g. neutrophil extracellular traps formation). However, the immune system also requires a tight regulation, as an overshooting immune response carries the risk of harming the host itself. This reviewaims at highlighting the unique features and molecular mechanisms that allow for the interactions of platelets and leucocytes and the regulation of this process. Furthermore, this article identifies the functional relevance of these events for the immune response. [ABSTRACT FROM AUTHOR]

Diffuse parenchymal lung diseases (DPLDs) are characterized by chronic inflammation and fibrotic remodeling of the interstitial tissue. A small fraction of DPLD cases can be genetically defined by mutations in certain genes, with ABCA3 being the gene most commonly affected. However, the pathomechanisms underlying ABCA3-induced DPLD are far from clear. To investigate whether ABCA3 plays a role in cellular cholesterol homeostasis, phospholipids, free cholesterol, and cholesteryl esters were quantified in cells stably expressing ABCA3 using mass spectrometry. Cellular free cholesterol and lipid droplets were visualized by filipin or oil red staining, respectively. Expression of SREBP regulated genes was measured using qPCR. Cell viability was assessed using the XTT assay. We found that wild type ABCA3 reduces cellular free cholesterol levels, induces the SREBP pathway, and renders cells more resistant to loading with exogenous cholesterol. Moreover, ABCA3 mutations found in patients with DPLD interfere with this protective effect of ABCA3, resulting in free cholesterol induced cell death. We conclude that ABCA3 plays a previously unrecognized role in the regulation of cellular cholesterol levels. Accumulation of free cholesterol as a result of a loss of ABCA3 export function represents a novel pathomechanism in ABCA3-induced DPLD. [ABSTRACT FROM AUTHOR]

IMPORTANCE No interventions have yet been identified to reduce the risk of acute kidney injury in the setting of cardiac surgery. OBJECTIVE To determine whether remote ischemic preconditioning reduces the rate and severity of acute kidney injury in patients undergoing cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS In this multicenter trial, we enrolled 240 patients at high risk for acute kidney injury, as identified by a Cleveland Clinic Foundation score of 6 or higher, between August 2013 and June 2014 at 4 hospitals in Germany. We randomized them to receive remote ischemic preconditioning or sham remote ischemic preconditioning (control). All patients completed follow-up 30 days after surgery and were analyzed according to the intention-to-treat principle. INTERVENTIONS Patients received either remote ischemic preconditioning (3 cycles of 5-minute ischemia and 5-minute reperfusion in one upper arm after induction of anesthesia) or sham remote ischemic preconditioning (control), both via blood pressure cuff inflation. MAIN OUTCOMES AND MEASURES The primary end point was the rate of acute kidney injury defined by Kidney Disease: Improving Global Outcomes criteria within the first 72 hours after cardiac surgery. Secondary end points included use of renal replacement therapy, duration of intensive care unit stay, occurrence of myocardial infarction and stroke, in-hospital and 30-day mortality, and change in acute kidney injury biomarkers. RESULTS Acute kidney injury was significantly reduced with remote ischemic preconditioning (45 of 120 patients [37.5%]) compared with control (63 of 120 patients [52.5%]; absolute risk reduction, 15%; 95% CI, 2.56%-27.44%; P = .02). Fewer patients receiving remote ischemic preconditioning received renal replacement therapy (7 [5.8%] vs 19 [15.8%]; absolute risk reduction, 10%; 95% CI, 2.25%-17.75%; P = .01), and remote ischemic preconditioning reduced intensive care unit stay (3 days [interquartile range, 2-5]) vs 4 days (interquartile range, 2-7) (P = .04). There was no significant effect of remote ischemic preconditioning on myocardial infarction, stroke, or mortality. Remote ischemic preconditioning significantly attenuated the release of urinary insulinlike growth factor-binding protein 7 and tissue inhibitor of metalloproteinases 2 after surgery (remote ischemic preconditioning, 0.36 vs control, 0.97 ng/mL2/1000; difference, 0.61; 95% CI, 0.27-0.86; P < .001). No adverse events were reported with remote ischemic preconditioning. CONCLUSIONS AND RELEVANCE Among high-risk patients undergoing cardiac surgery, remote ischemic preconditioning compared with no ischemic preconditioning significantly reduced the rate of acute kidney injury and use of renal replacement therapy. The observed reduction in the rate of acute kidney injury and the need for renal replacement warrants further investigation. [ABSTRACT FROM AUTHOR]

In the 10 years since schema therapy was first recognized in Germany it has become widespread among practitioners and has taken a place among the so-called third wave therapies. The overall goal of schema therapy is conceptualizing and treating personality disorders or traits reinforcing axis I disorders. Early maladaptive schemas result from a child's unmet emotional core needs. In a limited reparenting therapy relationship these interpersonal situations are re-experienced and rescripted under the therapist's control. Schema therapy integrates elements of existing models and techniques into a consistent case conceptualization as the bedrock for understanding and changing maladaptive coping behavior. This review article gives a comprehensive overview about the model, the therapy relationship and the application of the experiential techniques in relation to already developed approaches (including the current evidence). The strengths and weaknesses are briefly discussed. [ABSTRACT FROM AUTHOR]

By the late 1970s, eutrophic conditions in Tampa Bay raised concerns by many local stakeholders and led to the establishment of the Agency on Bay Management (ABM). In 1991, the Tampa Bay National Estuary Program (NEP) continued the ABM efforts, particularly as they addressed the Bay's water quality problems. The NEP Water Quality Subcommittee recognized the need to identify, and importantly quantify, the pollutant sources responsible for those water quality problems. As a result, the NEP facilitated and led a stakeholder effort to address excess nutrient loading. Seven primary nitrogen sources were identified, including domestic and industrial point sources, nonpoint sources, groundwater and springs, the loading due to fertilizer handling at the bay ports, and atmospheric deposition. Tampa Bay managers and scientists early recognized the potential effect of atmospheric deposition of nitrogen on estuarine loading. Consistent loading estimation methods were applied to a long-term record beginning in 1985, and monthly loading estimates have been reported every year since. This long-term record has allowed the assessment of how population growth and land use change have affected the bay. Other critical drivers that have also been examined include the Grizzle-Figg Act of 1978 and the statewide permitting requirements for non-agricultural stormwater systems enacted in 1986. Local ordinances such as those that limit fertilizer use can also be assessed. The effects of El Nino rains and the unexpected loading due to spills have also been put into the context of the natural variability in nitrogen loading. This paper will present the long-term trends in nitrogen loading to each of the seven bay segments and show how the bay has responded to the variation in loading over time. We also examine how they have been applied as part of the management of Tampa Bay water quality. [ABSTRACT FROM AUTHOR]

The article explores the selection of endpoints to use for clinical trials in acute kidney injury (AKI). It describes the use of AKI itself as the primary endpoint in prevention or diagnostic trials. It also discusses the inclusion of biomarkers in the definition of endpoints and the application of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for AKI.

The incidence of acute kidney injury (AKI) in critically ill patients is very high and is associated with an increased morbidity and mortality. In 2012 the Kidney Disease: Improving Global Outcome (KDIGO) guidelines were published in which evidence-based practical recommendations are given for the evaluation and management of patients with AKI. The first section of the KDIGO guidelines deals with the unification of earlier consensus definitions and staging criteria for AKI. The subsequent sections of the guidelines cover the prevention and treatment of AKI as well as the management of renal replacement therapy (RRT) in patients with AKI. In each section the existing evidence is discussed and a specific treatment recommendation is given. The guidelines appreciates that there is insufficient evidence for many of the recommendations. As a specific pharmacological therapy is missing, an early diagnosis, aggressive hemodynamic optimization, tight volume control, and avoidance of nephrotoxic drugs are the only interventions to prevent AKI. If renal replacement therapy is required different modalities are available to provide an effective therapy with a low rate of adverse effects. [ABSTRACT FROM AUTHOR]

The incidence of acute kidney injury (AKI) in critically ill patients is very high and is associated with an increased morbidity and mortality. In 2012 the Kidney Disease: Improving Global Outcome (KDIGO) guidelines were published in which evidence-based practical recommendations are given for the evaluation and management of patients with AKI. The first section of the KDIGO guidelines deals with the unification of earlier consensus definitions and staging criteria for AKI. The subsequent sections of the guidelines cover the prevention and treatment of AKI as well as the management of renal replacement therapy (RRT) in patients with AKI. In each section the existing evidence is discussed and a specific treatment recommendation is given. The guidelines appreciates that there is insufficient evidence for many of the recommendations. As a specific pharmacological therapy is missing, an early diagnosis, aggressive hemodynamic optimization, tight volume control, and avoidance of nephrotoxic drugs are the only interventions to prevent AKI. If renal replacement therapy is required different modalities are available to provide an effective therapy with a low rate of adverse effects. [ABSTRACT FROM AUTHOR]

Integrins are recognized as vital players in leukocyte recruitment. Integrin malfunction causes severe disease patterns characterized by the inability to fight pathogens. Although inflammatory reactions are beneficial and necessary for host defense, these reactions have to be controlled to prevent tissue destruction and harmful sequelae. In this review, we discuss the different signaling pathways leading to the change of integrin adhesiveness in neutrophils, monocytes, and lymphocytes. We thereby focus on the importance of integrin activation for the different steps of the leukocyte recruitment cascade, including rolling, adhesion, postadhesion strengthening, intravascular crawling, and transmigration, as each step necessitates the proper functioning of a distinct set of integrin molecules that has to be activated specifically. Additionally, we discuss endogenous mechanisms that balance and counteract integrin activation and limit leukocyte recruitment at the site of inflammation. Further insight into these complex mechanisms may provide new approaches for developing new anti-inflammatory therapies. [ABSTRACT FROM AUTHOR]

The wound healing response after myocardial infarction (MI) involves a cascade of molecular and cellular events that lead to a replacement of the necrotic area with a collagen-rich scar. Clearance of necrotic debris by neutrophils, monocytes, and macrophages is a critical component of infarct healing; however, tight control and timely repression of this inflammatory response is important to prevent excessive tissue degradation leading to infarct expansion and heart failure. Genetic ablation or blockade of anti-inflammatory pathways tends to be detrimental after MI, whereas genetic ablation of pro-inflammatory pathways tends to be beneficial. Accordingly, therapies enhancing endogenous anti-inflammatory pathways or blocking endogenous pro-inflammatory pathways have been found to improve wound healing and to reduce the risk of heart failure in rodent models of acute MI. Besides their scavenger function, inflammatory cells promote healing by stimulating angiogenesis and granulation tissue formation via paracrine factors. Moreover, signaling mediators that are active in inflammatory cells may be active also in non-inflammatory cell types involved in infarct healing. Some anti-inflammatory interventions are therefore deleterious. However, interventions that carefully adjust the balance between the essential and detrimental facets of inflammation may provide new therapeutic opportunities for patients with large MIs who continue to be at risk of developing heart failure, despite modern reperfusion and anti-remodeling strategies. [ABSTRACT FROM AUTHOR]

Leukocyte recruitment into tissue forms the basis of immune surveillance and direct immune defense. It proceeds in a cascade-like fashion. The first contact of leukocytes with the endothelium is mediated by selectins and their counter receptors, followed by rolling and integrin-mediated arrest. While rolling, neutrophils collect different inflammatory signals which can activate several signaling pathways leading to leukocyte adhesion to the endothelium and transmigration through the blood vessel wall into the inflamed tissue. Whereas inflammatory reactions are beneficial and necessary for host defense, they need to be balanced and controlled to prevent harmful consequences and tissue destruction. In this article, we discuss the different signaling pathways that ensure rapid and efficient integrin activation on leukocytes. In addition, we report on a recently identified novel endogenous mechanism that counteracts and balances integrin activation, thereby limiting leukocyte recruitment and the extent of inflammation. Further investigation of this new mechanism may allow providing new approaches for the development of the next generation of anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Recruitment of leukocytes into inflamed tissue is a key component of the immune system. The activation of integrins on leukocytes is required for their recruitment into the inflamed tissue. Btk is a cytoplasmic nonreceptor tyrosine kinase belonging to the Tec-kinase family. It plays a key role in B-cell development and function, and recently published studies revealed important roles of Btk in myeloid cells. Btk might be activated through a variety of receptors leading to activation of integrins as the pivotal element in leukocyte recruitment. This review focuses on the role of Btk in B-lymphocyte homing and in neutrophil recruitment. [ABSTRACT FROM AUTHOR]

Hintergrund: Die Psychotherapieausbildung wird mehr und mehr zum Gegenstand empirischer Forschung. In Deutschland hat sich die Psychotherapeutenausbildung nach Inkrafttreten des Psychotherapeutengesetzes erheblich verändert. In Bezug auf die neuen Ausbildungsgänge beginnt nun die Phase der empirischen Evaluation. Ziel der vorliegenden Studie war es, zu dieser Entwicklung im Hinblick auf die Ausbildung in der Verhaltenstherapie (VT) beizutragen. Methode: Eine Stichprobe von n = 2106 Ausbildungskandidaten in VT konnte mit einem Fragebogen zu Ausbildungsbedingungen, Ausbildungserfahrungen und subjektiven Kompetenzerwartungen in Bezug auf psychotherapeutische Kompetenzen befragt werden. Der Fragebogen wurde in Anlehnung an Instrumente zum Hochschulranking in einem mehrstufigen Prozess entwickelt. Durch hierarchische, mehrfach lineare Regressionsanalysen wurde versucht, 5 psychotherapeutische Kompetenzbereiche durch soziodemografische, ausbildungsbezogene und institutionsstrukturelle Prädiktoren vorherzusagen. Ergebnisse: Insgesamt war die erklärte Varianz gering. Ein als angemessen beurteiltes Aufwand/Nutzen-Verhältnis bei der Ausbildung und die persönliche Unterstützung durch einen kompetenten Supervisor konnten jedoch in allen untersuchten Kompetenzbereichen signifikant zur Erklärung der Varianz beitragen. Schlussfolgerungen: Um unterschiedliche Bedürfnisse von Ausbildungskandidaten zu berücksichtigen, sollten unterschiedliche Ausbildungsangebote gemacht werden. Persönliche Unterstützung in der Supervision durch einen erfahrenen Kollegen ist wesentlich für die Entwicklung einer positiven professionellen Kompetenzerwartung. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]