Determination of glomerular filtration rate "en passant" after high doses of iohexol for computed tomography in intensive care medicine-a proof of concept.

Accurate assessment of renal function is of great clinical and scientific importance, as it is an important pharmacokinetic covariate of pivotal drugs. The iohexol clearance is nearly identical to the glomerular filtration rate, but its determination usually requires an intravenous injection and therefore bears intrinsic risks. This motivates to showcase an "en passant" approach to quantification of renal function without additional risk or blood sampling beyond routine care using real-world data. We enrolled 37 intensive care patients who received high doses of iohexol for computed tomography imaging, and quantified series of iohexol plasma concentrations by high-performance liquid chromatography (HPLC-UV). Iohexol clearance was derived by both log-linear regression and nonlinear least squares fitting and compared to glomerular filtration rate estimated by the CKD-EPI-2021 formulas. Nonlinear fitting not only turned out to be more accurate but also more robust in handling the irregularly timed data points. Concordance of iohexol clearance against estimations based on both creatinine and cystatin C showed a slightly higher bias (-3.44 mL/min/1.73 m2) compared to estimations based on creatinine alone (-0.76 mL/min/1.73 m2), but considerably narrower limits of agreement (±42.8 vs. 56 mL/min/1.73 m2) and higher Lin's correlation (0.84 vs. 0.72). In summary, we have demonstrated the feasibility and performance of the "en passant" variant of the iohexol method in intensive care medicine and described a working protocol for its application in clinical practice and pharmacologic studies.

Array-Based Comparative Genomic Hybridization for the Detection of Copy Number Alterations in Single Cells.

Comprehensive genome-wide analyses of single cells represent an important tool for clinical applications, such as pre-implantation diagnostic and prenatal diagnosis, as well as for cancer research purpose. For the latter, studies of tumor heterogeneity, circulating tumor cells (CTCs), and disseminated cancer cells (DCCs) require the analysis of single-cell genomes. Here we describe a reliable and robust array-based comparative genomic hybridization (aCGH) protocol based on Ampli 1™ whole genome amplification that allows the detection of copy number alterations (CNAs) in single cancer cells as small as 100 kb.

Isolation and Genomic Analysis of Circulating Tumor Cell Clusters in Cancer Patients.

The role of circulating tumor cell (CTC) clusters in the metastatic dissemination process is gaining increased attention. Besides homotypic clusters, heterotypic clusters that contain tumor cells admixed with normal cells are frequently observed in patients with solid tumors. Current methods used for cluster detection and enumeration do not allow an accurate estimation of the relative fractions of tumor cells. Here we describe a method for estimating tumor fraction of clusters including isolation and collection of single clusters, assessment of copy number alterations of single clusters by low-pass whole genome sequencing, and bioinformatic analysis of sequencing data.

The benefits of haptic feedback in robot assisted surgery and their moderators: a meta-analysis.

Robot assisted surgery (RAS) provides medical practitioners with valuable tools, decreasing strain during surgery and leading to better patient outcomes. While the loss of haptic sensation is a commonly cited disadvantage of RAS, new systems aim to address this problem by providing artificial haptic feedback. N = 56 papers that compared robotic surgery systems with and without haptic feedback were analyzed to quantify the performance benefits of restoring the haptic modality. Additionally, this study identifies factors moderating the effect of restoring haptic sensation. Overall results showed haptic feedback was effective in reducing average forces (Hedges' g = 0.83) and peak forces (Hedges' g = 0.69) applied during surgery, as well as reducing the completion time (Hedges' g = 0.83). Haptic feedback has also been found to lead to higher accuracy (Hedges' g = 1.50) and success rates (Hedges' g = 0.80) during surgical tasks. Effect sizes on several measures varied between tasks, the type of provided feedback, and the subjects' levels of surgical expertise, with higher levels of expertise generally associated with smaller effect sizes. No significant differences were found between virtual fixtures and rendering contact forces. Implications for future research are discussed.

Zero-fluoro atrioventricular-nodal reentrant tachycardia ablation.

BACKGROUND: Atrioventricular-nodal reentrant tachycardia (AVNRT) is a common supraventricular tachycardia, particularly in younger patients. The treatment of choice is radiofrequency catheter ablation (RFCA), traditionally necessitating ionizing radiation for catheter guidance. OBJECTIVE: The authors aimed to demonstrate the feasibility and safety of zero-fluoroscopy RFCA of AVNRT using EnSite™ NavX™ as a three-dimensional (3D) electroanatomical mapping system (EAM). METHODS: The authors retrospectively analyzed 68 patients that underwent AVNRT-RFCA. One group was a priori allocated to conventional fluoroscopy mapping (convFluoro, n = 30). In 38 cases, the electrophysiologist chose to use 3D-EAM for ablation. Of these patients, 20 could be ablated without fluoroscopy use (zeroFluoro). In 18 cases that were initially intended as 3D-EAM, additional fluoroscopy use was necessary due to difficult anatomic conditions (convertedFluoro). Procedure duration, fluoroscopy duration and dose, as well as complications were analyzed. RESULTS: Procedure duration was similar for the convFluoro and zeroFluoro groups (74 ± 24 min vs. 80 ± 26 min, p = ns). The convertedFluoro group showed longer procedure duration compared to the convFluoro group (94 ± 30 min vs. 74 ± 24 min, p < 0.05). The use of 3D-EAM significantly reduced fluoroscopy duration comparing the convFluoro with the convertedFluoro group (12 ± 9 min vs. 7 ± 6 min, p < 0.05). The difference in fluoroscopy dose between convFluoro and convertedFluoro did not reach significance (169 ± 166 cGycm2 vs. 134 ± 137 cGycm2, p = ns). In zeroFluoro cases, no radiation was used at all. 3D-EAM-guided RFCA was primarily successful in all patients. Overall, there were only few minor complications in the different groups. No major complications occurred. CONCLUSION: Zero-fluoro RFCA in patients with AVNRT is feasible and safe. 3D-EAM can reduce radiation exposure in the majority of patients without prolonging procedure duration or increasing complications.

Clinical Insights into the Treatment of Patellofemoral Instability with Medial Patellofemoral Ligament Reconstruction: Pearls and Pitfalls-Lessons Learned from 20 Years.

Patellofemoral instability is a prevalent cause of pain and disability in young individuals engaged in athletic activities. Adolescents face a particularly notable risk of patellar dislocation, which can be attributed to rapid skeletal growth, changes in q-angle, ligamentous laxity, higher activity levels, and increased exposure to risk. Specific sports activities carry an elevated risk of patellar dislocation. Younger age and trochlear dysplasia present the highest risk factors for recurrent patellar dislocations. International guidelines recommend conservative therapy following a single patellar dislocation without osteochondral lesions but suggest surgical intervention in recurrent cases. In this study, we have compiled current scientific data on therapy recommendations, focusing on MPFL (medial patellofemoral ligament) reconstruction. We discuss patient selection, surgical indications, graft selection, location and choice of fixation, graft tensioning, and postoperative care.

Frame-rate reduction to reduce radiation dose for cardiac device implantation is safe.

Background: Radiation exposure to patient and surgeon during cardiac implantable electrical device (CIED) procedures remains a substantial health hazard to date. Advanced technical options for radiation dose reduction often pose considerable financial hurdles. We propose a near-zero cost, low-effort modification to a clinical x-ray system significantly reducing radiation dose during CIED implantation. Objective: We aim to evaluate a reduced frame rate protocol in CIED implantation for complication rates and reduction in radiation exposure. Methods: Starting May 2019, the frame rate during CIED implantations at our hospital was halved from 7.5 frames/s to 3.8 frames/s, and no further technical changes were made. During the following year, 264 patients were operated using this protocol and retrospectively compared with 231 cases implanted in the year before the protocol change, totaling 495 cases. Of these, 17%, 63%, and 19% were single-chamber, dual-chamber, or resynchronization devices, respectively. Incidence of complication prior to hospital discharge was considered the primary endpoint of the analysis. Radiation dose and procedural parameters were secondary endpoints. Results: There was no increase in complications with the reduced frame rate protocol. Regression analysis further supported that the reduced frame rate radiation protocol was not associated with complication rates. Radiation exposure measured as dose area product was significantly reduced by ∼62% (median 369 [interquartile range 154-1207] cGy·cm2 via the reduced frame rate protocol vs median 970 [interquartile range 400-1906] cGy·cm2 with the standard frame rate; P < 0.01). Conclusion: A reduction of frame rate during CIED implantation is safe in terms of complication incidence and effective in terms of reducing radiation exposure.

Intraoperative suggestions to prevent postoperative delirium in patients undergoing transaortic valvular replacement: a randomized placebo-controlled trial.

BACKGROUND: Postoperative delirium (POD) is a serious complication following anaesthesia and surgery and significantly influences postoperative outcome especially in the elderly population. Intraoperative music and positive suggestions influence postoperative outcomes by attenuating analgesic demand and increasing patient satisfaction. AIMS: Here, we examined the effect of intraoperative music and positive suggestions on the development of POD in aged patients undergoing transcatheter aortic valve replacement (TAVR) procedure under general anaesthesia. METHODS: For this randomized placebo-controlled study, eligible patients without cognitive deficit, indicated by a MMSE < 10 points, were anesthetized using remifentanil and sevoflurane. Anaesthetic depth was guide with bispectral index. An audiotape with positive suggestions was applied from a MP3 player via headphones. POD, pain and PONV was assessed. CAM-ICU and Nu-DESC were done twice daily for the first 5 days. RESULTS: Of 140 patients 118 patients could be analysed (57 male, 80.6 ± 5.1 years). POD was diagnosed in 16 patients (12.7%). POD was significantly more often observed in male (12, 21.1%) than in female (4, 6.6%, p = 0.02) and in patients with a low MMSE (23.6 ± 4.5 vs. 26.8 ± 2.8, p = 0.001). Anaesthetic depth did not influence the incidence of POD. Intraoperative music and suggestions did not affect the rate of POD, pain, analgesic requirement or PONV. DISCUSSION: In patients undergoing TAVR male sex and low MMSE scoring are associated with an increase in POD. CONCLUSIONS: Intraoperative music and positive suggestions do not influence the incidence of POD in this patient group. STUDY REGISTRATION: DRKS: 00024444, start of registration: 4.02.202, final registration: 17.09.2021.

Efficacy of CytoSorb®: a systematic review and meta-analysis.

INTRODUCTION: Cytokine adsorption using the CytoSorb® adsorber has been proposed in various clinical settings including sepsis, ARDS, hyperinflammatory syndromes, cardiac surgery or recovery after cardiac arrest. The aim of this analysis is to provide evidence for the efficacy of the CytoSorb® adsorber with regard to mortality in various settings. METHODS: We searched PubMed, Cochrane Library database and the database provided by Cytosorbents™ (01.1.2010-29.5.2022). We considered randomized controlled trials and observational studies with control groups. The longest reported mortality was defined as the primary endpoint. We computed risk ratios and 95%-confidence intervals and used DerSimonian and Lairds random effects model. We analysed all studies combined and divided them into the subgroups: sepsis, cardiopulmonary bypass surgery (CPB), other severe illness, SARS-CoV-2 infection and recovery from cardiac arrest. The meta-analysis was registered in advance (PROSPERO: CRD42022290334). RESULTS: Of an initial 1295 publications, 34 studies were found eligible, including 1297 patients treated with CytoSorb® and 1314 controls. Cytosorb® intervention did not lower mortality (RR [95%-CI]: all studies 1.07 [0.88; 1.31], sepsis 0.98 [0.74; 1.31], CPB surgery 0.91 [0.64; 1.29], severe illness 0.95 [0.59; 1.55], SARS-CoV-2 1.58 [0.50; 4.94]). In patients with cardiac arrest, we found a significant survival advantage of the untreated controls (1.22 [1.02; 1.46]). We did not find significant differences in ICU length of stay, lactate levels, or IL-6 levels after treatment. Of the eligible 34 studies only 12 were randomized controlled trials. All observational studies showed moderate to serious risk of bias. INTERPRETATION: To date, there is no evidence for a positive effect of the CytoSorb® adsorber on mortality across a variety of diagnoses that justifies its widespread use in intensive care medicine.

Long-term effects of retrograde approach on the knee after motorized femoral limb lengthening.

BACKGROUND AND PURPOSE: The retrograde femoral approach is an established technique for implantation of nails for leg lengthening and correction and in cases of distal femoral fractures. The purpose of this study was to determine the 10-year outcome of this technique by analyzing the clinical long-term effects and radiological status of the knee after leg lengthening via a retrograde femoral approach. PATIENTS AND METHODS: This retrospective single-center study included 13 patients (median age at surgery 17 [range 15-20] years) who underwent unilateral, retrograde, femoral lengthening with a motorized nail. Outcome measurements were graded variables of the SF-36, ISKD score, and Lysholm score. MRI of both knees was performed in all patients. MRI was evaluated for the presence of degenerative changes and compared with the healthy contralateral knee. Cartilage condition was graded according to the International Cartilage Repair Society (ICRS) scoring system. RESULTS: All patients were pain-free and had a full range of motion 10 (range 10.0-12.2) years after surgery. All postoperative knees showed fibrosis of Hoffa's fat pad and moderate to severe cartilage defects (ICRS Grade 2-4) of the trochlear groove (nail entry site). 6 out of 13 operated knees exhibited retropatellar cartilage defects. CONCLUSION: Our study showed that patients were pain-free, but cartilage defects at the entry point and arthrofibrosis at Hoffa's fat pad were observed without causing clinical impairment.

Comparative analysis of EpCAM high-expressing and low-expressing circulating tumour cells with regard to their clonal relationship and clinical value.

BACKGROUND: Circulating tumour cells (CTCs) are mainly enriched based on the epithelial cell adhesion molecule (EpCAM). Although it was shown that an EpCAM low-expressing CTC fraction is not captured by such approaches, knowledge about its prognostic and predictive relevance and its relation to EpCAM-positive CTCs is lacking. METHODS: We developed an immunomagnetic assay to enrich CTCs from metastatic breast cancer patients EpCAM independently using antibodies against Trop-2 and CD-49f and characterised their EpCAM expression. DNA of single EpCAM high expressing and low expressing CTCs was analyzed regarding chromosomal aberrations and predictive mutations. Additionally, we compared CTC-enrichment on the CellSearch system using this antibody mix and the EpCAM based enrichment. RESULTS: Both antibodies acted synergistically in capturing CTCs. Patients with EpCAM high-expressing CTCs had a worse overall and progression-free survival. EpCAM high- and low-expressing CTCs presented similar chromosomal aberrations and mutations indicating a close evolutionary relationship. A sequential enrichment of CTCs from the EpCAM-depleted fraction yielded a population of CTCs not captured EpCAM dependently but harbouring predictive information. CONCLUSIONS: Our data indicate that EpCAM low-expressing CTCs could be used as a valuable tumour surrogate material-although they may be prognostically less relevant than EpCAM high-expressing CTCs-and have particular benefit if no CTCs are detected using EpCAM-dependent technologies.

Concomitant Valve Replacement and Coronary Artery Bypass Grafting Surgery: Lessons from the Past, Guidance for the Future? A Mortality Analysis in 294 Patients.

OBJECTIVE: The aims of this study were to analyze parameters influencing early and late mortality after concomitant valve replacement and coronary artery bypass grafting surgery, using early and long-term information from an institutionally available data registry, and to discuss the results in relation to the current treatment strategies and perspectives. METHODS: The study population consisted of 294 patients after combined valve replacement with mechanical prosthesis and CABG surgery. RESULTS: There were 201 men (68.4%) and 93 women (31.6%). Concurrent to the coronary artery bypass grafting, 238 patients (80.9%) underwent aortic-, 46 patients (15.6%) mitral- and 10 patients (3.4%) doublevalve replacement. Cumulative duration of follow up was 1007 patient-years (py) with a maximum of 94 months and was completed in 92.2% (271 cases). Overall hospital mortality (30 days) rate was 6.5% (n = 19). It was significantly higher in patients of female gender, older than 70 y, in those suffering preoperative myocardial infarction, presenting with an additive EuroScore > 8 and being hemodynamically unstable after the operation. Cumulative survival rate at 7.6 y was 78.6%. Determinants of prolonged survival were male gender, age at operation < 70 y, preoperative sinus rhythm, normal renal function, additive EuroScore < 8 and the use of internal thoracic artery for grafting. Subsequent multivariate analysis revealed preoperative atrial fibrillation (HR: 2.1, 95% CI: 0.82-5.44, p: 0.01) and risk group of ES > 8 (HR: 3.63, 95% CI: 1.45-9.07, p < 0.01) as independent predictors for lower long-term survival. CONCLUSIONS: Hospital mortality (30 d) was nearly 2.5-fold higher in female and/or older than 70 y patients. Preoperative atrial fibrillation and/ or a calculated ES > 8 were independent predisposing factors of late mortality for combined VR and CABG surgery. Tailoring the approach, with the employment of the newest techniques and hybrid procedures, to the individual patient clinical profile enables favorable outcomes for concomitant valvular disease and CAD, especially in high-risk patients.

Design and synthesis of a tetracyclic tripeptide mimetic frozen in a polyproline type II (PP2) helix conformation.

A synthesis of the new tetracyclic scaffold ProM-19, which represents a XPP tripeptide unit frozen in a PPII helix conformation, was developed. As a key building block, N-Boc-protected ethyl (1S,3S,4R)-2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate was prepared through a diastereoselective aza-Diels-Alder reaction and subsequent hydrogenolytic removal of the chiral N-1-phenylethyl substituent under temporary protection of the double bond through dihydroxylation and reconstitution by Corey-Winter olefination. The target compound Boc-[ProM-19]-OMe was then prepared via subsequent peptide coupling and Ru-catalyzed ring-closing metathesis steps employing (S)-N-Boc-allylgylcine and cis-5-vinyl-proline methyl ester as additional building blocks. In addition, Ac-[2-Cl-Phe]-[Pro]-[ProM-19]-OMe was prepared by solution phase peptide synthesis as a potential ligand for the ena-VASP EVH1 domain.

Prospective randomized trial of skin closure for pacemaker implantation: absorbable vs. non-absorbable suture : PRO-PACE.

BACKGROUND: Pacemaker implantations have been performed for > 50 years, reaching 1.25 million implants worldwide per year. Despite this, only few randomized studies exist regarding technical aspects of the implantation procedure-in particular, wound closure. Accordingly, the authors compared absorbable vs. non-absorbable suture regarding wound healing. METHODS: Consecutive patients scheduled for de novo pacemaker implantation without defibrillation therapy were prospectively randomized into two groups: non-absorbable (Prolene®, Ethicon Inc.) or absorbable suture (Monocryl®, Ethicon Inc.). The wound was systematically assessed for cosmetic outcome at 1 day, 6 weeks, and 1 year post implantation using the patient and observer scar assessment scale (POSAS). Adverse events noted included bleeding, pocket hematoma, infection, suture insufficiency, and revision surgery. RESULTS: A total of 114 patients (mean age: 79 ± 10 years, n = 60 male) were randomized into the two groups. Of these, 105 completed follow-up (lost to follow-up: 7.9%). Groups were comparable for clinical characteristics or use of oral anticoagulants. There was no difference in cosmetic outcome and incidence of adverse events at any follow-up visit. POSAS scores were: 1 day: 1.4 ± 0.4 vs. 1.3 ± 0.4, P = 0.44, 6 weeks: 1.4 ± 0.6 vs. 1.4 ± 0.7, P = 0.57; 1 year: 1.4 ± 1.4 vs. 2.1 ± 3, P = 0.60. No pocket hematoma or infection occurred in either group. No additional surgery was necessary for local findings. Retrospectively, scar development was straight in the Prolene® group and slightly wavy with Monocryl®. CONCLUSION: Suture material does not influence wound healing as represented by the cosmetic result and the occurrence of adverse events. The choice of suture material used should be left to the physician's discretion.

Renal events in patients receiving neprilysin inhibitors: a systematic review and meta-analysis.

BACKGROUND: While it is well known that angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs) increase the risk of acute renal failure, the role of neprilysin inhibition (NEPi) is unclear and some physicians are reluctant to prescribe sacubitril/valsartan because of safety concerns. This meta-analysis aimed to examine the risk for renal events, progression of chronic kidney disease (CKD) or progression to dialysis on combined NEPi and ACEi/ARBs compared with ACEi or ARBs. METHODS: We performed a systematic meta-analysis including 17 randomized controlled trials (study drug sacubitril/valsartan or omapatrilat), involving a total of 23 569 patients, after searching PubMed, Cochrane, ClinicalTrials.org and Embase for eligible studies. From the included trials, all renal endpoints, including long- and short-term outcomes and hyperkalemia, were extracted. Pooled odds ratios (ORs) were calculated using the DerSimonian and Laird method. The study was registered at PROSPERO. RESULTS: Overall, treatment with sacubitril/valsartan or omapatrilat showed a slightly lower risk of any renal event [OR 0.82 (0.7-0.97)] compared with treatment with an ACEi or ARB alone. Also, there was a decreased risk of severe acute renal events [OR 0.8 (0.69-0.93)] and a decrease in estimated glomerular filtration rate decline [mean difference -0.58 mL/min (-0.83 to -0.33 mL/min)]. There was no difference in chronic renal events [OR 0.92 (0.8-1.05)] or hyperkalemia [OR 1.02 (0.84-1.23)]. CONCLUSION: NEPi + ACEi/ARBs are safe in terms of renal adverse events. Longer trials focusing on CKD are needed to evaluate the effect of NEPi on decreasing progression of CKD.

[Insulin autoimmune syndrome : A rare, but important differential diagnosis of hypoglycemia]. / Insulinautoimmunsyndrom : Eine seltene, aber wichtige Differentialdiagnose der Hypoglykämie.

A 69-year-old female patient was referred to the Medical University of Hanover for further diagnostic evaluation of recurrent severe hypoglycemia. The patient had previously been started on clopidogrel after arterial stenting for peripheral arterial obstructive disease (PAOD). The presence of an insulinoma and paraneoplastic syndrome was excluded. Increased serum insulin and insulin autoantibodies levels were confirmed, despite normal to low blood sugar levels. An insulin autoimmune syndrome was diagnosed, most likely induced by the prior intake of clopidogrel. Treatment with immunoadsorption was initiated, achieving a significant reduction in hypoglycemic events and a lasting response to treatment over 3 months.

Renal Recovery after the Implementation of an Electronic Alert and Biomarker-Guided Kidney-Protection Strategy following Major Surgery.

Background: The facilitation of early recovery of acute kidney injury (AKI) is an important step to improve outcome, particularly because of the limited therapeutic interventions currently available for AKI. The combination of an electronic alert and biomarker-guided kidney-protection strategy implemented in the routine care may have an impact on the incidence of early complete reversal of AKI after major non-cardiac surgery. Methods: We studied 294 patients in two cohorts before (n = 151) and after protocol implementation (n = 143). Data collection required 6 months for each cohort. The kidney-protection protocol included an electronic alert to detect patients who were eligible for urinary biomarker [TIMP2 × IGFBP7]-guided kidney-protection intervention. Intervention was stratified according to three levels of immediate AKI risk: low, moderate, and high. After intervention, postoperative changes in the glomerular filtration rate (eGFR) were identified with a tracking software that included an alert for nephrology consultation if the eGFR had declined by >25% from the preoperative reference value. Primary outcome was early AKI recovery, i.e., the complete reversal of any AKI stage to absence of AKI within the first 7 postoperative days. Results: Protocol implementation significantly increased the recovery of AKI (36/46, 78% compared to control 27/48, 56%, (p = 0.025)) and reduced the length of the ICU stay (p < 0.001). There was no significant difference in the overall incidence of all AKI and moderate and severe AKI in the first 7 postoperative days: 46/143 (32%) and 12/151 (8%) in the protocol implementation group compared to 48/151 (32%) and 18/151 (12%) in the historical control group. Patients with AKI reversal within the first 7 postoperative days had lower in-hospital mortality than patients without AKI reversal. Conclusions: Implementing a combined electronic alert and biomarker-guided kidney-protection strategy in routine care improved early recovery of AKI after major surgery.

Neutron Diffraction Study of a Sintered Iron Electrode In Operando.

Iron is a promising, earth-abundant material for future energy applications. In this study, we use a neutron diffractometer to investigate the properties of an iron electrode in an alkaline environment. As neutrons penetrate deeply into materials, neutron scattering gives us a unique insight into what is happening inside the electrode. We made our measurements while the electrode was charging or discharging. Our key questions are: Which phases occur for the first and second discharge plateaus? And why are iron electrodes less responsive at higher discharge rates? We conclude that metallic iron and iron hydroxide form the redox pair for the first discharge plateau. For the second discharge plateau, we found a phase similar to feroxyhyte but with symmetrical and equally spaced arrangement of hydrogen atoms. The data suggest that no other iron oxide or iron (oxy)hydroxide formed. Remarkable findings include the following: (1) substantial amounts of iron hydroxide are always present inside the electrode. (2) Passivation is mostly caused by iron hydroxide that is unable to recharge. (3) Iron fractions change as expected, while iron hydroxide fractions are delayed, resulting in substantial amounts of amorphous, undetectable iron phases. About 40% of the participating iron of the first plateau and about 55% of the participating iron for the second plateau are undetectable. (4) Massive and unexpected precipitation of iron hydroxide occurs in the transition from discharging to charging. (2), (3), and (4) together cause accumulation of iron hydroxide inside the electrode.

The additional use of methylene blue has a decatecholaminisation effect on cardiac vasoplegic syndrome after cardiac surgery.

BACKGROUND: Postoperative vasoplegia with minimal responsiveness to vasopressors is common after cardiac surgery. Called cardiac vasoplegic syndrome (CVS), it is caused by multiple factors. Treating CVS involves a high dose of fluids and catecholamines, however high doses of catecholamines and fluids are associated with serious side effects. There is evidence that new therapeutic strategies can lead to a reduction in norepinephrine doses and mortality in CVS. Specifically, the use of non-adrenergic vasopressors such as methylene blue (MB) can be beneficial. METHODS: We retrospectively analyzed the electronic records of 8716 adult cardiac surgery patients from November 2008 to December 2016. Medication, hemodynamic and outcome parameter data were analyzed for CVS until discharge. We determined CVS according to the following parameters: a postoperative onset of ≤24 h, a reduced mean arterial pressure (MAP) of < 70 mmHg, a dose of norepinephrine ≥0.8 mg*h- 1 and a continuously increasing need for catecholamine, without ventricular dysfunction. RESULTS: We identified 513 patients with CVS. Perioperative risk factors were higher in patients treated with methylene blue (MB). Before MB administration patients had a significantly higher dose of norepinephrine, and MAP increased after MB administration. Norepinephrine could be reduced after MB administration and MAP remained stable at the same level even after the reduction of norepinephrine. CONCLUSIONS: CVS patients have a severe systemic disease accompanied by significant operative stress and a high catecholamine requirement. The administration of MB in addition to standard treatment for CVS in the first 24 h was accompanied by an increase in MAP followed by a decrease in vasopressor requirement, indicating that early MB administration can be beneficial.