Bilateral Femoral Cannulation Is Associated With Reduced Severe Limb Ischemia-Related Complications Compared With Unilateral Femoral Cannulation in Adult Peripheral Venoarterial Extracorporeal Membrane Oxygenation: Results From the Extracorporeal Life Support Registry.

OBJECTIVES: Peripheral venoarterial extracorporeal membrane oxygenation (ECMO) with femoral access is obtained through unilateral or bilateral groin cannulation. Whether one cannulation strategy is associated with a lower risk for limb ischemia remains unknown. We aim to assess if one strategy is preferable. DESIGN: A retrospective cohort study based on the Extracorporeal Life Support Organization registry. SETTING: ECMO centers worldwide included in the Extracorporeal Life Support Organization registry. PATIENTS: All adult patients (≥ 18 yr) who received peripheral venoarterial ECMO with femoral access and were included from 2014 to 2020. INTERVENTIONS: Unilateral or bilateral femoral cannulation. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the occurrence of limb ischemia defined as a composite endpoint including the need for a distal perfusion cannula (DPC) after 6 hours from implantation, compartment syndrome/fasciotomy, amputation, revascularization, and thrombectomy. Secondary endpoints included bleeding at the peripheral cannulation site, need for vessel repair, vessel repair after decannulation, and in-hospital death. Propensity score matching was performed to account for confounders. Overall, 19,093 patients underwent peripheral venoarterial ECMO through unilateral ( n = 11,965) or bilateral ( n = 7,128) femoral cannulation. Limb ischemia requiring any intervention was not different between both groups (bilateral vs unilateral: odds ratio [OR], 0.92; 95% CI, 0.82-1.02). However, there was a lower rate of compartment syndrome/fasciotomy in the bilateral group (bilateral vs unilateral: OR, 0.80; 95% CI, 0.66-0.97). Bilateral cannulation was also associated with lower odds of cannulation site bleeding (bilateral vs unilateral: OR, 0.87; 95% CI, 0.76-0.99), vessel repair (bilateral vs unilateral: OR, 0.55; 95% CI, 0.38-0.79), and in-hospital mortality (bilateral vs unilateral: OR, 0.85; 95% CI, 0.81-0.91) compared with unilateral cannulation. These findings were unchanged after propensity matching. CONCLUSIONS: This study showed no risk reduction for overall limb ischemia-related events requiring DPC after 6 hours when comparing bilateral to unilateral femoral cannulation in peripheral venoarterial ECMO. However, bilateral cannulation was associated with a reduced risk for compartment syndrome/fasciotomy, lower rates of bleeding and vessel repair during ECMO, and lower in-hospital mortality.

Potential utility of renal functional reserve testing in clinical nephrology.

PURPOSE OF REVIEW: The aim of this review is to discuss the concept of renal functional reserve (RFR) and its potential relevance in clinical practice. RECENT FINDINGS: The RFR is a measure of the change in glomerular filtration rate (GFR) from baseline to a peak value when the kidney is stimulated to increase its function. This concept has a strong physiologic basis in nephrology and the presence, magnitude or absence of RFR capacity may have prognostic significance in many clinical scenarios where individuals are at risk of hyperfiltration or kidney dysfunction. Unlike in other medical specialties, where organ reserve function is reliably measurable and used routinely, measurement of RFR in nephrology has not been integrated into clinical care. Methodologic challenges including standardization of methods to stimulate GFR and the ability of measures of GFR to discriminate acute dynamic changes in GFR upon kidney stimulation have hampered the robustness and use of RFR measurements in research and clinical care. SUMMARY: Given the emergence of many new disease-modifying therapies in nephrology, it is imperative that we move forward and develop more robust tools to further our understanding of kidney physiology and pathophysiology, such as the RFR, which should be integrated into research and clinical care to support optimal personalization of therapeutic kidney care strategies.

Donor Evaluation Tool: A New Technology Improves Donor Enrolment on ICU.

Uncertainties on the intensive care unit (ICU) regarding the eligibility of a patient to be a potential deceased organ donor may prevent their referral and enrolment in the pathway for organ donation. Healthcare staff may exclude potential donors for medical reasons, which are no longer applicable. Hence, Swisstransplant implemented a digital donor evaluation tool (DET) in 2021, which allows the local hospital's organ donation coordinator to send a direct request to medical advisors (MA) of the organ procurement organization before excluding potential donors. All 156 requests entered in 2022 were analyzed. 117 patients (75.0%) were primarily accepted by the MA as potential donors. Of those 60 patients (51.3%) became actual organ donors. Main reasons for using the DET were questions regarding malignancies (n = 33, 21.2%), infectious diseases (n = 35, 22.4%) and age/co-morbidities (n = 34, 21.8%). The average age of the actual "DET donor" compared to the regularly enrolled, actual "Non-DET donor" was 65.3 ± 15.8 vs. 56.8 ± 17.5 years, respectively (p = 0.008). On average 1.9 ± 1.1 organs compared to 3.2 ± 1.3 organs were retrieved from DET vs. Non-DET donors. In summary, this new digital donor evaluation tool supports reporting and facilitates eligibility decisions in uncertain, complex donor cases, potentially increasing the number of organ donations.

Initial outcomes and surgical techniques of prostatic urethral lift for benign prostatic hyperplasia in Japan.

OBJECTIVES: The prostatic urethral lift (PUL) has been used as a minimally invasive surgery for benign prostatic hyperplasia (BPH) since April 2022 in Japan. This study evaluated the initial outcomes and surgical techniques of PUL for BPH. METHODS: In this prospective, single-center study, indications were based on the proper use guidelines for PUL in Japan. Preoperative patient status, postoperative progress at 1 and 3 months, and perioperative complications were evaluated. The surgical technique was changed twice, and the subgroup analysis and technique were evaluated. RESULTS: Of the 50 patients who underwent surgeries performed by a single surgeon, the median age and prostate volume were 71 years and 42.0 mL, respectively. Furthermore, the median operative time and number of implants used were 20 min and 5, respectively. No postoperative fever or severe hematuria requiring reoperation occurred. All patients were discharged from the hospital the day following the PUL, as scheduled. Postoperative International Prostate Symptom Score, quality of life score, maximum flow rate, and postvoid residual volume at 1 and 3 months were significantly improved compared with the preoperative values. A significant improvement in maximum flow rate was observed in the subgroup analysis from 1 month postoperatively in the group with an anterior channel creation focus. CONCLUSIONS: PUL is effective and safe in cases with prostate volumes of <100 mL. Lifting the bladder neck is important for opening an anterior prostatic urethral channel and improving urinary function during the early postoperative period.

F16 Hybrids Derived from Steviol or Isosteviol Are Accumulated in the Mitochondria of Tumor Cells and Overcome Drug Resistance.

Steviol and isosteviol were prepared from the commercially available sweetener stevioside and converted into lipophilic F16 hybrids. Their cytotoxicity was determined in SRB assays and showed to depend on both the substitution pattern of the aromatic substituent as well as on the spacer length. Therefore, compound 25 held an IC50 (A2780) of 180 nM, thus surpassing the activity of comparable rhodamine hybrids. Several of the compounds were also able to overcome drug resistance in the A2780/A2780cis model. Extra staining experiments showed a similar subcellular accumulation pattern of the F16 hybrids as a well-established mitocan, hence proving preferential mitochondrial accumulation but also some other accumulation in other cellular areas.

On antigen-specific signals, immune class regulation and energetics: Report III from the workshops on foundational concepts of immune regulation.

This is a report from a one-week workshop held in Athens, Greece in July of 2022. The workshop aimed to identify emerging concepts relevant to the fundamentals of immune regulation and areas for future research. Theories of immune regulation emphasize the role of T cell help or co-stimulation (signal 2). The workshop participants considered how new data on the characteristics of agonist antigens, the role of the antigen receptor signals (signal 1) in driving fate decisions, the effect of energetics on immunity and a better understanding of class-control in the immune response, may impact theories of immune regulation. These ideas were discussed in the context of tumour immunology, autoimmunity, pregnancy and transplantation. Here we present the discussions as a narrative of different viewpoints to allow the reader to join the conversation. These discussions highlight the evolving understanding of the nature of specific antigen recognition and how both antigen-specific and non-specific mechanisms impact immune responses.

Access to expensive therapies and diagnostics for kidney care in Switzerland.

BACKGROUND: In Switzerland, nephrologists must frequently obtain pre-authorizations from health insurers for certain medications/tests for individual patients. These are time consuming and outcomes are inconsistent. Clinical experience suggest inequities in access to expensive medications, related to need for and processes involved with medication pre-authorization requests. METHODS: An anonymous survey was conducted between November 2021 and March 2022 regarding experiences in applying for pre-authorizations for medications and genetic testing required for kidney care conducted among nephrologists in Switzerland. RESULTS: Ninety-four responses were received. The most common medications reported to require pre-approvals were rituximab, sodium glucose cotransporter-2 inhibitors (SGLT2i), mycophenolate mofetil (MMF) and eculizumab. Rebuttals were reported to be most frequently required for rituximab, eculizumab and SGLT2i, also the most frequently denied medications. Most frequent genetic testing requests were for complement and Alports spectrum disorders. Requests for genetic testing were reported to be most frequently denied for cystic renal diseases, congenital syndromes and nephrotic syndrome.Most nephrologists found requests for further information from the health insurers were seldom reasonable; 72% reported it was rarely/never possible to engage with the insurance physicians, 69% were concerned insurance physicians did not have relevant expertise. Respondents reported receiving different responses from different insurers for similar requests more frequently than from the same insurer (58% vs 8%). One in three nephrologists reported that the pre-authorizations process frequently resulted in a clinically relevant delay in treatment. Four of five respondents reported that the pre-authorization process frequently made them feel that they could not do their best for the patient. CONCLUSION: From the perspective of nephrologists, the pre-authorizations process in Switzerland is cumbersome, not transparent and inequitable, may result in denial or delays of important treatment for patients and contributes to moral distress.

Dehydroabietylamine-substituted trifluorobenzene sulfonamide rhodamine B hybrids as anticancer agents overcoming drug resistance.

Attachment of a conjugate assembled from a novel fluorinated carbonic anhydrase inhibitor and rhodamine B onto dehydroabietylamine (DHA) or cyclododecylamine led to first-in-class conjugates of good cytotoxicity; thereby IC50 values (from SRB assays; employed tumor cell lines A2780, A2780Cis, A549, HT29, MCF7, and non-malignant human fibroblasts CCD18Co) between 0.2 and 0.7 µM were found. Both conjugates showed similar cytotoxic activity but the dehydroabietylamine derived conjugate outperformed its cyclododecyl analog in terms of tumor cell/non-tumor cell selectivity. Both conjugates accumulate intracellular, and the DHA conjugate was able to overcome drug resistance which is effective independent of the expression status of carbonic anhydrase IX.

Neutrophil extracellular traps - a potential trigger for the development of thrombocytopenia during extracorporeal membrane oxygenation.

Neutrophil extracellular traps (NETs) have recently emerged as a potential link between inflammation, immunity, and thrombosis, as well as other coagulation disorders which present a major challenge in the context of extracorporeal membrane oxygenation (ECMO). By examining blood from ECMO patients for NETs and their precursors and correlating them with clinical and laboratory biomarkers of coagulation and inflammation, this study aims to evaluate the association between the presence of NETs in the bloodstream of ECMO patients and the development of potentially severe coagulation disorders during ECMO therapy. Therefore, blood samples were collected from healthy volunteers (n=13) and patients receiving veno-venous (VV) ECMO therapy (n=10). To identify NETs and their precursors, DNA and myeloperoxidase as well as granulocyte marker CD66b were visualized simultaneously by immunofluorescence staining in serial blood smears. Differentiation of DNA-containing objects and identification of NETs and their precursors was performed semiautomatically by a specific algorithm using the shape and size of DNA staining and the intensity of MPO and CD66b signal. Neutrophil extracellular traps and their precursors could be detected in blood smears from patients requiring VV ECMO. Compared to volunteers, ECMO patients presented significantly higher rates of NETs and NET precursors as well as an increased proportion of neutrophil granulocytes in all detected nucleated cells. A high NET rate prior to the initiation of ECMO therapy was associated with both increased IL-6 and TNF-α levels as an expression of a high cytokine burden. These patients with increased NET release also presented an earlier and significantly more pronounced decrease in platelet counts and ATIII activity following initiation of therapy compared with patients with less elevated NETs. These findings provide further indications for the development of immune-mediated acquired thrombocytopenia in ECMO patients.

Prostatic urethral lift for subjects in urinary retention (PULSAR): 12-Month results of a prospective controlled trial compared with real-world outcomes.

Objective: To examine the safety and efficacy of prostatic urethral lift (PUL) in acute urinary retention (AUR) patients within a controlled (PULSAR) and real-world setting (Real-World Retrospective study). Materials and methods: PULSAR was a 12-month prospective study of PUL in AUR patients (n = 51) performed at six centres in the United Kingdom; enrolled BPH patients aged ≥50 years, with prostate volume of ≤100 cc. AUR was defined as being catheter dependent with at least one prior failed trial without catheter (TWOC) while on an alpha-blocker. RWR consisted of 3226 consecutive PUL patients across 22 international sites treated between July 2017 and March 2020; 469 of whom were in urinary retention (RWRr), that is, catheter-dependent at the time of their procedure. Symptom response, uroflow and catheter independence rates were compared between PULSAR and RWRr subjects. A logistical regression model was constructed to evaluate patient baseline and dynamic factors predicting success after the procedure. Results: Seventy-three percent of PULSAR subjects were catheter independent and free from surgical reintervention at 12 months post-PUL. Success was associated with higher voiding efficiency during the perioperative period. Slightly higher catheter-independent rates (80%) were seen in RWRr patients; variables that influenced success included age <70 years, lower baseline prostate-specific antigen (PSA), lower baseline post-void residual (PVR) and shorter pre-procedural catheter duration. Logistic regression of the combined PULSAR and RWRr retention groups revealed that procedural age <70 years and higher bladder voiding efficiency (BVE) were associated with success. Conclusions: Lower baseline PSA and PVR, younger age and shorter pre-procedure catheter durations drove successful outcomes in AUR patients undergoing PUL. Post-PUL voiding efficiencies may help ascertain long-term response to treatment.

Functionalized magnetic nanoparticles remove donor-specific antibodies (DSA) from patient blood in a first ex vivo proof of principle study.

The presence of donor-specific antibodies (DSA) such as antibodies directed against donor class I human leucocyte antigen (e.g., HLA-A) is a major barrier to kidney transplant success. As a proof of concept, functionalized magnetic nanoparticles have been designed to eliminate DSA from saline, blood and plasma of healthy donors and sensitized patients. Specific HLA-A1 protein was covalently bound to functionalized cobalt nanoparticles (fNP), human serum albumin (HSA) as control. fNP were added to anti-HLA class I-spiked saline, spiked volunteers' whole blood, and to whole blood and plasma of sensitized patients ex vivo. Anti-HLA-A1 antibody levels were determined with Luminex technology. Antibodies' median fluorescent intensity (MFI) was defined as the primary outcome. Furthermore, the impact of fNP treatment on blood coagulation and cellular uptake was determined. Treatment with fNP reduced MFI by 97 ± 2% and by 94 ± 4% (p < 0.001 and p = 0.001) in spiked saline and whole blood, respectively. In six known sensitized anti-HLA-A1 positive patients, a reduction of 65 ± 26% (p = 0.002) in plasma and 65 ± 33% (p = 0.012) in whole blood was achieved. No impact on coagulation was observed. A minimal number of nanoparticles was detected in peripheral mononuclear blood cells. The study demonstrates-in a first step-the feasibility of anti-HLA antibody removal using fNP. These pilot data might pave the way for a new personalized DSA removal technology in the future.

Refractory circulatory failure in COVID-19 patients treated with veno-arterial ECMO a retrospective single-center experience.

OBJECTIVE: In this retrospective case series, survival rates in different indications for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and differential diagnoses of COVID-19 associated refractory circulatory failure are investigated. METHODS: Retrospective analysis of 28 consecutive COVID-19 patients requiring VA-ECMO. All VA-ECMO's were cannulated peripherally, using a femoro-femoral cannulation. RESULTS: At VA-ECMO initiation, median age was 57 years (IQR: 51-62), SOFA score 16 (IQR: 13-17) and norepinephrine dosing 0.53µg/kg/min (IQR: 0.35-0.87). Virus-variants were: 61% wild-type, 14% Alpha, 18% Delta and 7% Omicron. Indications for VA-ECMO support were pulmonary embolism (PE) (n = 5, survival 80%), right heart failure due to secondary pulmonary hypertension (n = 5, survival 20%), cardiac arrest (n = 4, survival 25%), acute heart failure (AHF) (n = 10, survival 40%) and refractory vasoplegia (n = 4, survival 0%). Among the patients with AHF, 4 patients suffered from COVID-19 associated heart failure (CovHF) (survival 100%) and 6 patients from sepsis associated heart failure (SHF) (survival 0%). Main Complications were acute kidney injury (AKI) 93%, renal replacement therapy was needed in 79%, intracranial hemorrhage occurred in 18%. Overall survival to hospital discharge was 39%. CONCLUSION: Survival on VA-ECMO in COVID-19 depends on VA-ECMO indication, which should be considered in further studies and clinical decision making. A subgroup of patients suffers from acute heart failure due to inflammation, which has to be differentiated into septic or COVID-19 associated. Novel biomarkers are required to ensure reliable differentiation between these entities; a candidate might be soluble interleukin 2 receptor.

Combination of Betulinic Acid Fragments and Carbonic Anhydrase Inhibitors-A New Drug Targeting Approach.

Human carbonic anhydrase IX (hCA IX) is a zinc(II)-dependent metalloenzyme that plays a critical role in the conversion of carbon dioxide and water to protons and bicarbonate. It is a membrane-bound protein with an extracellular catalytic center that is predominantly overexpressed in solid hypoxic tumors. Sulfamates and sulfonamides, for example acetazolamide (AZA), have been used to inhibit hCA IX in order to improve the response to solid hypoxic tumors. In the present study, we propose a new drug targeting approach by attaching the natural cytotoxic substances betulin and betulinic acid (BA) via a linker to sulfonamides. The conjugate was designed with different spacer lengths to accumulate at the target site of hCA IX. Computational and cell biological studies suggest that the length of the linker may influence hCA IX inhibition. Cytotoxicity tests of the newly synthesized bifunctional conjugates 3, 5, and 9 show effective cytotoxicity in the range of 6.4 and 30.1 µM in 2D and 3D tumor models. The hCA IX inhibition constants of this conjugates, measured using an in vitro enzyme assay with p-nitrophenyl acetate, were determined in a low µM-range, and all compounds reveal a significant inhibition of hypoxia-induced CA activity in a cell-based assay using the Wilbur-Anderson method. In addition, the cells respond with G1 increase and apoptosis induction. Overall, the dual strategy to produce cytotoxic tumor therapeutics that inhibit tumor-associated hCA IX was successfully implemented.

Age and associated outcomes among patients receiving venovenous extracorporeal membrane oxygenation for acute respiratory failure: analysis of the Extracorporeal Life Support Organization registry.

PURPOSE: Venovenous extracorporeal membrane oxygenation (VV-ECMO) can be used to support patients with refractory acute respiratory failure, though guidance on patient selection is lacking. While age is commonly utilized as a factor in establishing the potential VV-ECMO candidacy of these patients, little is known regarding its association with outcome. We studied the association between increasing patient age and outcomes among patients with acute respiratory failure receiving VV-ECMO. METHODS: In this registry-based cohort study, we used individual patient data from 144 centres. We included adult patients (≥ 18 years of age) receiving VV-ECMO from 2017 to 2022. The primary outcome was hospital mortality. Secondary outcomes included a composite of complications following initiation of VV-ECMO. We conducted Bayesian analyses to estimate the association between chronological age and outcomes. RESULTS: We included 27,811 patients receiving VV-ECMO. Of these, 11,533 (41.5%) died in hospital. For the analysis conducted using weakly informed priors, and as compared to the reference category of age 18-29, the age brackets of 30-39 (odds ratio [OR] 1.17, 95% credible interval [CrI] 1.06-1.31), 40-49 (OR 1.65, 95% CrI 1.49-1.82), 50-59 (OR 2.39, 95% CrI 2.16-2.61), 60-69 (OR 3.29, 95% CrI 2.97-3.67), 70-79 (OR 4.57, 95% CrI 3.90-5.37), and ≥ 80 (OR 8.08, 95% CrI 4.85-13.74) were independently associated with increasing hospital mortality. Similar results were found between increasing age and post-ECMO complications. CONCLUSIONS: Among patients receiving VV-ECMO for acute respiratory failure, increasing age is significantly associated with poorer outcomes, and this association emerges as early as 30 years of age.

Frequency and impact on renal transplant outcomes of urinary tract infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species.

Background: Enterobacterales are often responsible for urinary tract infection (UTI) in kidney transplant recipients. Among these, Escherichia coli or Klebsiella species producing extended-spectrum beta-lactamase (ESBL) are emerging. However, there are only scarce data on frequency and impact of ESBL-UTI on transplant outcomes. Methods: We investigated frequency and impact of first-year UTI events with ESBL Escherichia coli and/or Klebsiella species in a prospective multicenter cohort consisting of 1,482 kidney transplants performed between 2012 and 2017, focusing only on 389 kidney transplants having at least one UTI with Escherichia coli and/or Klebsiella species. The cohort had a median follow-up of four years. Results: In total, 139/825 (17%) first-year UTI events in 69/389 (18%) transplant recipients were caused by ESBL-producing strains. Both UTI phenotypes and proportion among all UTI events over time were not different compared with UTI caused by non-ESBL-producing strains. However, hospitalizations in UTI with ESBL-producing strains were more often observed (39% versus 26%, p = 0.04). Transplant recipients with first-year UTI events with an ESBL-producing strain had more frequently recurrent UTI (33% versus 18%, p = 0.02) but there was no significant difference in one-year kidney function as well as longer-term graft and patient survival between patients with and without ESBL-UTI. Conclusion: First-year UTI events with ESBL-producing Escherichia coli and/or Klebsiella species are associated with a higher need for hospitalization but do neither impact allograft function nor allograft and patient survival.

European practices on antithrombotic management during percutaneous mechanical circulatory support in adults: a survey of the Association for Acute CardioVascular Care of the ESC and the European branch of the Extracorporeal Life Support Organization.

AIMS: Bleeding and thrombotic complications compromise outcomes in patients undergoing percutaneous mechanical circulatory support (pMCS) with veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and/or microaxial flow pumps like Impella™. Antithrombotic practices are an important determinant of the coagulopathic risk, but standardization in the antithrombotic management during pMCS is lacking. This survey outlines European practices in antithrombotic management in adults on pMCS, making an initial effort to standardize practices, inform future trials, and enhance outcomes. METHODS AND RESULTS: This online cross-sectional survey was distributed through digital newsletters and social media platforms by the Association of Acute Cardiovascular Care and the European branch of the Extracorporeal Life Support Organization. The survey was available from 17 April 2023 to 23 May 2023. The target population were European clinicians involved in care for adults on pMCS. We included 105 responses from 26 European countries. Notably, 72.4% of the respondents adhered to locally established anticoagulation protocols, with unfractionated heparin (UFH) being the predominant anticoagulant (Impella™: 97.0% and V-A ECMO: 96.1%). A minority of the respondents, 10.8 and 14.5%, respectively, utilized the anti-factor-Xa assay in parallel with activated partial thromboplastin time for UFH monitoring during Impella™ and V-A ECMO support. Anticoagulant targets varied across institutions. Following acute coronary syndrome without percutaneous coronary intervention (PCI), 54.0 and 42.7% were administered dual antiplatelet therapy during Impella™ and V-A ECMO support, increasing to 93.7 and 84.0% after PCI. CONCLUSION: Substantial heterogeneity in antithrombotic practices emerged from participants' responses, potentially contributing to variable device-associated bleeding and thrombotic complications.

Renal mass imaging modalities: does body mass index (BMI) matter?

PURPOSE: Accurate measurement of renal mass size is crucial in the management of renal cancer. With the burdensome cost of imaging yet its need for management, a better understanding of the variability among patients when determining mass size remains of urgent importance. Current guidelines on optimal imaging are limited, especially with respect to body mass index (BMI). The aim of this study is to discern which modalities accurately measure renal mass size and whether BMI influences such accuracy. METHODS: A multi-institutional chart review was performed for adult patients undergoing partial or radical nephrectomy between 2018 and 2021, with 236 patients ultimately included. Patients were categorized by BMI (BMI 1: 18.5-24.9, BMI 2: 25-29.9, BMI 3: 30-34.9, and BMI 4: ≥ 35). The greatest mass lengths were compared between the pathology report and the following: computerized tomography (CT), renal ultrasound, and magnetic resonance imaging (MRI). RESULTS: The difference between greatest length on CT with contrast and MRI were significantly different when compared to pathologic measurement. BMI groups 3 and 4 were found to have a significant difference in size estimates compared to BMI 2 for CT with contrast. No difference was found between size estimates by BMI group for any other imaging modality. CONCLUSION: CT with contrast becomes less accurate at estimating mass size for patients with BMI > 30. While contrast-enhanced CT remains a vital imaging modality for tissue enhancement in the context of unknown renal masses, caution must be used for mass size estimation in the obese population.

Extracorporeal Life Support Organization Registry International Report 2022: 100,000 Survivors.

The Extracorporeal Life Support Organization (ELSO) maintains the world's largest extracorporeal membrane oxygenation (ECMO) registry by volume, center participation, and international scope. This 2022 ELSO Registry Report describes the program characteristics of ECMO centers, processes of ECMO care, and reported outcomes. Neonates (0-28 days), children (29 days-17 years), and adults (≥18 years) supported with ECMO from 2009 through 2022 and reported to the ELSO Registry were included. This report describes adjunctive therapies, support modes, treatments, complications, and survival outcomes. Data are presented descriptively as counts and percent or median and interquartile range (IQR) by year, group, or level. Missing values were excluded before calculating descriptive statistics. Complications are reported per 1,000 ECMO hours. From 2009 to 2022, 154,568 ECMO runs were entered into the ELSO Registry. Seven hundred and eighty centers submitted data during this time (557 in 2022). Since 2009, the median annual number of adult ECMO runs per center per year increased from 4 to 15, whereas for pediatric and neonatal runs, the rate decreased from 12 to 7. Over 50% of patients were transferred to the reporting ECMO center; 20% of these patients were transported with ECMO. The use of prone positioning before respiratory ECMO increased from 15% (2019) to 44% (2021) for adults during the coronavirus disease-2019 (COVID-19) pandemic. Survival to hospital discharge was greatest at 68.5% for neonatal respiratory support and lowest at 29.5% for ECPR delivered to adults. By 2022, the Registry had enrolled its 200,000th ECMO patient and 100,000th patient discharged alive. Since its inception, the ELSO Registry has helped centers measure and compare outcomes across its member centers and strategies of care. Continued growth and development of the Registry will aim to bolster its utility to patients and centers.

α-Synuclein Oligomers Displace Monomeric α-Synuclein from Lipid Membranes.

Parkinson's disease (PD) is an increasingly prevalent and currently incurable neurodegenerative disorder linked to the accumulation of α-synuclein (αS) protein aggregates in the nervous system. While αS binding to membranes in its monomeric state is correlated to its physiological role, αS oligomerization and subsequent aberrant interactions with lipid bilayers have emerged as key steps in PD-associated neurotoxicity. However, little is known of the mechanisms that govern the interactions of oligomeric αS (OαS) with lipid membranes and the factors that modulate such interactions. This is in large part due to experimental challenges underlying studies of OαS-membrane interactions due to their dynamic and transient nature. Here, we address this challenge by using a suite of microfluidics-based assays that enable in-solution quantification of OαS-membrane interactions. We find that OαS bind more strongly to highly curved, rather than flat, lipid membranes. By comparing the membrane-binding properties of OαS and monomeric αS (MαS), we further demonstrate that OαS bind to membranes with up to 150-fold higher affinity than their monomeric counterparts. Moreover, OαS compete with and displace bound MαS from the membrane surface, suggesting that disruption to the functional binding of MαS to membranes may provide an additional toxicity mechanism in PD. These findings present a binding mechanism of oligomers to model membranes, which can potentially be targeted to inhibit the progression of PD.