Carboxylic acids in the hindgut of rats fed highly soluble inulin and Bifidobacterium lactis (Bb-12), Lactobacillus salivarius (UCC500) or Lactobacillus rhamnosus (GG)

Background: Propionic and butyric acids are important nutrients for the mucosal cells and may therefore increase the nutritional status and reduce the permeability of the colonic mucosa. These acids have also been suggested to counteract diseases in the colon, e.g. ulcerative colitis and colon cancer. Different substrates lead to different amounts and patterns of carboxylic acids (CAs). Objective: To study the effect of probiotics on CA formation in the hindgut of rats given inulin. Design: The rats were given inulin, marketed as highly soluble by the producer, together with the probiotic bacteria Bifidobacterium lactis (Bb-12), Lactobacillus salivarius (UCC500) or Lactobacillus rhamnosus (GG), or a mixture of all three. Results: Rats fed inulin only had comparatively high proportions of propionic and butyric acids throughout the hindgut. When diets were supplemented with Bb-12 and UCC500, the caecal pool of CAs increased compared with inulin only. In the caecum the proportion of butyric acid generally decreased when the rats were fed probiotics. In the distal colon the proportion of propionic and butyric acid was lower, while that of lactic acid was generally higher. The caecal pH in rats fed GG and Bb-12 was lower than expected from the concentration of CAs. Further, rats fed GG had the lowest weight gain and highest caecal tissue weight. Conclusions: It is possible to modify the formation of CAs by combining inulin with probiotics. Different probiotics had different effects

Are gadolinium-based contrast media really safer than iodinated media for digital subtraction angiography in patients with azotemia?

Gadolinium chelates, intended as intravenous contrast media for magnetic resonance imaging, have been regarded as nonnephrotoxic and recommended to replace iodinated contrast media in patients with azotemia who are undergoing digital subtraction angiography (DSA). High intraarterial doses (up to 220 mmol of gadodiamide) have been used, with a 40% incidence of nephropathy. The authors discourage the use of gadolinium for DSA for several reasons. (a) There exist no randomized studies comparing the nephrotoxic effects of gadolinium-based and iodinated media at equal-attenuating concentrations and doses. (b) Gadolinium-based media are hypertonic, a pathogenetic factor in contrast medium-induced nephropathy after renal angiography, with an osmolality two to seven times that of plasma. Iodinated media in concentrations that are equally attenuating with gadolinium-based media can be made isotonic. (c) In vitro measurements indicate that 0.5 mol/L gadolinium chelates are equally attenuating with 60-80 mg iodine per milliliter at the commonly used 70-90-kV range used for DSA. Thus, 50 mL of 0.5 mol/L gadolinium chelate ( approximately 0.3 mmol/kg in an 80-kg person) would be equally attenuating with a dose of 3-4 g of iodine in an iodinated medium (eg, 50 mL iohexol at 60-80 mg I/mL or 10-13 mL at 300 mg I/mL). (d) By combining these data on attenuation and results of toxicity studies in mice, the general toxicity of gadolinium chelates may be six to 25 times higher than that of equal-attenuating doses of iodinated media at 70-kV DSA. Thus, the authors believe that at equal-attenuating doses for DSA, modern iodinated contrast media should result in a lower toxic load on the body than with presently available gadolinium chelates

Estimated glomerular filtration rates are higher when creatinine-based equations are compared with a cystatin C-based equation in coronavirus disease 2019

Funding Information: The study was funded by the SciLifeLab/Knut and Alice Wallenberg national COVID‐19 research program (Michael Hultström; KAW 2020.0182, KAW 2020.0241), the Swedish Heart‐Lung Foundation (Michael Hultström; 20210089, 20190639, 20190637), the Swedish Research Council (Robert Frithiof; 2014‐02569, 2014‐07606), The Swedish Kidney Foundation (Robert Frithiof; F2020‐0054), and The Swedish Society of Medicine (Michael Hultström; SLS‐938101). Funding bodies had no role in the design of the study, data collection, interpretation, or in the writing of the article. Funding Information: Medicinska Forskningsrådet; SciLifeLab/Knut and Alice Wallenberg National COVID‐19 Research Program, Grant/Award Numbers: KAW 2020.0182, KAW 2020.0241; Swedish Heart‐Lung Foundation, Grant/Award Numbers: 20210089, 20190639, 20190637; Swedish Kidney Foundation, Grant/Award Number: F2020‐0054; Swedish Society of Medicine, Grant/Award Number: SLS‐938101; the Swedish Research Council, Grant/Award Numbers: 2014‐07606, 2014‐02569 Funding information Publisher Copyright: © 2022 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.Objectives: Estimations of glomerular filtration rate (eGFR) are based on analyses of creatinine and cystatin C, respectively. Coronavirus disease 2019 (COVID-19) patients in the intensive care unit (ICU) often have acute kidney injury (AKI) and are at increased risk of drug-induced kidney injury. The aim of this study was to compare creatinine-based eGFR equations to cystatin C-based eGFR in ICU patients with COVID-19. Methods: After informed consent, we included 370 adult ICU patients with COVID-19. Creatinine and cystatin C were analyzed at admission to the ICU as part of the routine care. Creatinine-based eGFR (ml/min) was calculated using the following equations, developed in chronological order; the Cockcroft–Gault (C-G), Modified Diet in Renal Disease (MDRD)1999, MDRD 2006, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Lund–Malmö revised (LMR) equations, which were compared with eGFR calculated using the cystatin C-based Caucasian Asian Pediatric Adult (CAPA) equation. Results: The median eGFR when determined by C-G was 99 ml/min and interquartile range (IQR: 67 ml/min). Corresponding estimations for MDRD1999 were 90 ml/min (IQR: 54); MDRD2006: 85 ml/min (IQR: 51); CKD-EPI: 91 ml/min (IQR: 47); and for LMR 83 ml/min (IQR: 41). eGFR was calculated using cystatin C and the CAPA equation value was 70 ml/min (IQR: 38). All differences between creatinine-based eGFR versus cystatin C-based eGFR were significant (p <.00001). Conclusions: Estimation of GFR based on various analyses of creatinine are higher when compared with a cystatin C-based equation. The C-G equation had the worst performance and should not be used in combination with modern creatinine analysis methods for determination of drug dosage in COVID-19 patients.publishersversionepub_ahead_of_prin

Persistent collateral perfusion of abdominal aortic aneurysm after endovascular repair does not lead to progressive change in aneurysm diameter

AbstractPurpose: To differentiate between the phenomenon of collateral perfusion from a side branch versus graft-related endoleaks after endovascular repair of abdominal aortic aneurysms (AAA), with respect to aneurysm size and prognosis. Methods: We successfully treated 64 AAA patients with endovascular grafting. We followed all the patients postoperatively with spiral computed tomography at one, three, six and 12 months, and biannually thereafter. We measured aneurysm diameters preoperatively and postoperatively. We calculated preoperatively the relation of maximum aortic diameter (D) to the thrombus-free lumen diameter (L) expressed as an L/D ratio. Median follow-up was 15 months. Results: Sixteen patients had collateral perfusion during follow-up. We successfully treated two patients with embolization. One patient showed resolution of collateral perfusion after we stopped warfarin treatment. Two patients died of unrelated causes during follow-up. One patient was converted to surgical treatment, and two patients showed spontaneous resolution of their collateral perfusion. The group of patients with perfusion showed no statistically significant change of their aortic diameter on follow-up. The group of patients without perfusion showed a median decrease in aortic diameter of 8mm (p < 0.0001) at 18 months postoperatively. The group of patients with perfusion had significantly less thrombus in their aneurysm sac preoperatively than the group without perfusion, as expressed by the L/D ratio (mean L/D 0,61 versus 0,78, respectively; p = 0.0021.) Conclusion: There was no significant increase in aortic diameter on an average 18 months postoperatively despite persistent collateral perfusion. This may indicate a halted disease progression in the short term. Embolization of collateral vessels is associated with risk of paraplegia. We recommend a conservative approach with close observation if aneurysm diameter is stable. (J Vasc Surg 1998;28:242-9.

Aortic dissection: Percutaneous management of ischemic complications with endovascular stents and balloon fenestration

AbstractPurpose: The purpose of this study was to evaluate endovascular stenting (EVS) and balloon fenestration (BF) of intimal flaps for the management of lower extremity, renal, and visceral ischemia in acute or chronic aortic dissection.Methods: Twenty-two patients (16 male, 6 female) with a median age of 53 years (range 35 to 77 years) underwent percutaneous treatment for peripheral ischemic complications of 12 type A (five acute, seven chronic) and 10 type B (nine acute, one chronic) aortic dissections.Results: Ten patients had leg ischemia, 13 had renal ischemia, and 6 had visceral ischemia. Sixteen patients were treated with EVS including 11 with renal, 6 with lower extremity, 2 with superior mesenteric artery, and 2 with aortic stents. Three patients had BF of the intimal flap, and three had BF in combination with EVS. Revascularization with clinical success was achieved in all 22 patients. Two patients died 3 days and 13.4 months after the procedure was performed, respectively. Of the remaining 20 patients, 1 is lost to follow-up, and 19 have persistent relief of clinical symptoms. Mean follow-up time is 13.7 months (range 1.1 to 46.5 months). One case was complicated by guidewire-induced perinephric hematoma.Conclusion: EVS and BF provide a safe and effective percutaneous method for managing peripheral ischemic complications of aortic dissection. (J VASC SURG 1996;23:241-53.

Endovascular repair of descending thoracic aortic aneurysms: an early experience with intermediate-term follow-up

AbstractPurpose: The purpose of this study was to report an initial experience with the endovascular repair of descending thoracic aortic aneurysm. Complications and intermediate-term morphologic changes were identified with the intent of altering patient selection and device design. Methods: Endografts were placed into 25 patients at high-risk for conventional surgical repair over a 3 ½–year period. Devices were customized on the basis of preoperative imaging information. Follow-up computed tomography scans were obtained at 1, 3, 6, and 12 months and yearly thereafter. Additional interventions occurred in the setting of endoleaks, migration, and aneurysm growth. Results: The overall 30-day mortality rate was 20% (12.5% for elective cases; 33% for emergent cases). There were 3 conversions to open repair. Neurologic deficits developed in 3 patients; 1 insult resulted in permanent paraplegia. Neurologic deficits were associated with longer endografts (P = .019). Three endoleaks required treatment, and 1 fatal rupture of the thoracic aneurysm treated occurred 6 months after the initial repair. Migrations were detected in 4 patients. The maximal aneurysm size decreased yearly by 9.15% (P = .01) or by 13.5% (P = .0005) if patients with endoleaks (n = 3 patients) were excluded. Both the proximal and distal neck dilated slightly over the course of follow-up (P = .019 and P = .001, respectively). The length of the proximal neck was a significant predictor of the risk for endoleakage (P = .02). Conclusion: The treatment of descending thoracic aortic aneurysms with an endovascular approach is feasible and may, in some patients, offer the best means of therapy. Early complications were primarily related to device design and patient selection. All aneurysms without endoleaks decreased in size after treatment. Late complications were associated with changing aneurysm morphologic features and device migration. The morphologic changes remain somewhat unpredictable; however, alterations in device design may result in improved fixation and more durable aneurysm exclusion. (J Vasc Surg 2000;31:147-56.

Nucleon-nucleon potential in finite nuclei

We consider the spin-isospin-independent central part of the residual nucleon-nucleon potential in finite spherical nuclei taking into account the deformation effects of the nucleons within the surrounding nuclear environment. It is shown that inside the nucleus the short-range repulsive contribution of the potential is increased and the intermediate attraction is decreased. We identify the growth of the radial component of the spin-isospin independent short-range part of the in-medium nucleon-nucleon interaction as the responsible agent that prevents the radial collapse of the nucleus.Comment: 9 pages, 3 eps figure

Study protocol for locoregional precision treatment of hepatocellular carcinoma with transarterial chemoembolisation (TACTida), a clinical study:idarubicin dose selection, tissue response and survival

INTRODUCTION: Hepatocellular carcinoma (HCC) is a common cause of cancer-related death, often detected in the intermediate stage. The standard of care for intermediate-stage HCC is transarterial chemoembolisation (TACE), where idarubicin (IDA) is a promising drug. Despite the fact that TACE has been used for several decades, treatment success is unpredictable. This clinical trial has been designed believing that further improvement might be achieved by increasing the understanding of interactions between local pharmacology, tumour targeting, HCC pathophysiology, metabolomics and molecular mechanisms of drug resistance. METHODS AND ANALYSIS: The study population of this single-centre clinical trial consists of adults with intermediate-stage HCC. Each tumour site will receive TACE with two different IDA doses, 10 and 15 mg, on separate occasions. Before and after each patient's first TACE blood samples, tissue and liquid biopsies, and positron emission tomography (PET)/MRI will be performed. Blood samples will be used for pharmacokinetics (PK) and liver function evaluation. Tissue biopsies will be used for histopathology analyses, and culturing of primary organoids of tumour and non-tumour tissue to measure cell viability, drug response, multiomics and gene expression. Multiomics analyses will also be performed on liquid biopsies. PET/MRI will be used to evaluate tumour viability and liver metabolism. The two doses of IDA will be compared regarding PK, antitumour effects and safety. Imaging, molecular biology and multiomics data will be used to identify HCC phenotypes and their relation to drug uptake and metabolism, treatment response and survival. ETHICS AND DISSEMINATION: Participants give informed consent. Personal data are deidentified. A patient will be withdrawn from the study if considered medically necessary, or if it is the wish of the patient. The study has been approved by the Swedish Ethical Review Authority (Dnr. 2021-01928) and by the Medical Product Agency, Uppsala, Sweden. TRIAL REGISTRATION NUMBER: EudraCT number: 2021-001257-31