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Journal of Cardiothoracic Surgery Apr 2024Open arch surgery is technically demanding for the surgeon and surgically and biologically invasive for the patient, requiring a variably long period of hypothermic...
BACKGROUND
Open arch surgery is technically demanding for the surgeon and surgically and biologically invasive for the patient, requiring a variably long period of hypothermic circulatory arrest.
CASE PRESENTATION
Here we present a case of an elderly patient with chronic renal failure and multiple splanchnic artery disease successfully treated for a rupturing pseudoaneurysm of the aortic arch with a technique that we developed for particularly frail patients. The procedure includes: triple supra-aortic vessel perfusion; distal thoracic aorta antegrade perfusion; balloon endo-clamping of the descending aorta; and anastomosis of an off-the-shelf hybrid arch prosthesis in Ishimaru zone 0. These maneuvers allowed to maintain an extracorporeal circulation in the phase of distal anastomosis, instead of a period of circulatory arrest, employing just mild hypothermia: technical details are depicted and discussed also in comparison with other methods proposed in the literature.
CONCLUSIONS
Being able to take advantage of both open surgery advancements and endovascular methods is the key to cardiovascular surgery success today in front of complex pathologies of the aorta: increasing safety and reducing invasiveness of therapeutic options may progressively extend surgical candidacy to the frailest patients.
Topics: Aged; Humans; Aorta, Thoracic; Aorta; Heart Arrest; Perfusion; Blood Vessel Prosthesis Implantation
PubMed: 38615049
DOI: 10.1186/s13019-024-02671-5 -
Nutrients Mar 2024Only some of the nutrients consumed with food are able to be absorbed from the gastrointestinal (GI) tract and enter the systemic circulation (blood). Because some...
Only some of the nutrients consumed with food are able to be absorbed from the gastrointestinal (GI) tract and enter the systemic circulation (blood). Because some elements are essential minerals for humans, their beneficial effect on the body depends significantly on their bioavailable amount (the fraction that can be absorbed and used by the organism). The term bioavailability, which is very often used to describe the part of nutrients that is able to be absorbed, is influenced by various factors of exogenous and endogenous origin. The main purpose of the study was to assess the relative bioavailability of Cr from selected dietary supplements in the presence of various types of diets, which significantly influence the level of bioavailability. The research was performed using a previously developed and optimized two-stage in vitro digestion model using cellulose dialysis tubes of food rations with the addition of pharmaceutical products. Cr was determined using the ICP-OES and GF-AAS methods, depending on its concentration in particular fractions. The determined relative bioavailability ranged between 2.97 and 3.70%. The results of the study revealed that the type of diet, the chemical form of the molecule, and the pharmaceutical form of preparations have a significant influence on the bioavailability of Cr.
Topics: Humans; Biological Availability; Poland; Renal Dialysis; Dietary Supplements; Nutrients
PubMed: 38613055
DOI: 10.3390/nu16071022 -
Computer Methods and Programs in... Jun 2024In the current work, we present a descriptive fluid-structure interaction computational study of the end-to-side radio-cephalic arteriovenous fistula. This allows us to...
BACKGROUND AND OBJECTIVE
In the current work, we present a descriptive fluid-structure interaction computational study of the end-to-side radio-cephalic arteriovenous fistula. This allows us to account for the different thicknesses and elastic properties of the radial artery and cephalic vein.
METHODS
The core of the work consists in simulating different arteriovenous fistula configurations obtained by virtually varying the anastomosis angle, i.e. the angle between the end of the cephalic vein and the side of the radial artery. Since the aim of the work is to understand the blood dynamics in the very first days after the surgical intervention, the radial artery is considered stiffer and thicker than the cephalic vein.
RESULTS
Our results demonstrate that both the diameter of the cephalic vein and the anastomosis angle play a crucial role to obtain a blood dynamics without re-circulation regions that could prevent fistula failure.
CONCLUSIONS
When an anastomosis angle close to the perpendicular direction with respect to the radial artery is combined with a large diameter of the cephalic vein, the recirculation regions and the low Wall Shear Stress (WSS) zones are reduced. Conversely, from a structural point of view, a low anastomosis angle with a large diameter of the cephalic vein reduces the mechanical stress acting on the vessel walls.
Topics: Humans; Arteriovenous Shunt, Surgical; Blood Flow Velocity; Radial Artery; Arteriovenous Fistula; Renal Dialysis; Treatment Outcome
PubMed: 38593514
DOI: 10.1016/j.cmpb.2024.108146 -
Journal of Clinical Medicine Feb 2024Renal cell carcinoma (RCC) is a common diagnosis, of which a notable portion of patients present with an extension into the venous circulation causing an inferior vena... (Review)
Review
Renal cell carcinoma (RCC) is a common diagnosis, of which a notable portion of patients present with an extension into the venous circulation causing an inferior vena cava (IVC) tumor thrombus. Venous extension has significant implications for staging and subsequent treatment planning, with recommendations for more aggressive surgical removal, although associated surgical morbidity and mortality is relatively increased. The methods for surgical removal of RCC with IVC thrombus remain complex, particularly surrounding the use of robot-assisted surgery. Robot assistance for radical nephrectomy in this context is recently emerging. Thrombus level has important implications for surgical technique and prognosis. Other preoperative considerations may include location, laterality, size, and wall invasion. The urology literature on treatment of such tumors is largely limited to case series and institutional studies that describe the feasibility of various surgical options for these complex tumors. Further understanding of the outcomes and patient-specific risk factors would shed increased light on the optimal treatment for such cases. This narrative review provides a thorough overview on the previously reported use of robot-assisted nephrectomy in RCC with IVC thrombus to inform further studies which may optimize outcomes and guide shared decision-making.
PubMed: 38592152
DOI: 10.3390/jcm13051308 -
Frontiers in Pharmacology 2024Fusion of the fragment crystallizable (Fc) to protein therapeutics is commonly used to extend the circulation time by enhancing neonatal Fc-receptor (FcRn)-mediated...
Fusion of the fragment crystallizable (Fc) to protein therapeutics is commonly used to extend the circulation time by enhancing neonatal Fc-receptor (FcRn)-mediated endosomal recycling and slowing renal clearance. This study applied kinetic modeling to gain insights into the cellular processing contributing to the observed pharmacokinetic (PK) differences between the novel recombinant ADAMTS13 fragment (MDTCS) and its Fc-fusion protein (MDTCS-Fc). For MDTCS and MDTCS-Fc, their plasma PK profiles were obtained at two dose levels following intravenous administration of the respective proteins to mice. The plasma PK profiles of MDTCS were fitted to a kinetic model with three unknown protein-dependent parameters representing the fraction recycled (FR) and the rate constants for endocytosis (k, for the uptake into the endosomes) and for the transfer from the plasma to the interstitial fluid (k). For MDTCS-Fc, the model was modified to include an additional parameter for binding to FcRn. Parameter optimization was done using the Cluster Gauss-Newton Method (CGNM), an algorithm that identifies multiple sets of approximate solutions ("accepted" parameter sets) to nonlinear least-squares problems. As expected, the kinetic modeling results yielded the FR of MDTCS-Fc to be 2.8-fold greater than that of MDTCS (0.8497 and 0.3061, respectively). In addition, MDTCS-Fc was predicted to undergo endocytosis (the uptake into the endosomes) at a slower rate than MDTCS. Sensitivity analyses identified the association rate constant (k) between MDTCS-Fc and FcRn as a potentially important factor influencing the plasma half-life . Our analyses suggested that Fc fusion to MDTCS leads to changes in not only the FR but also the uptake into the endosomes, impacting the systemic plasma PK profiles. These findings may be used to develop recombinant protein therapeutics with extended circulation time.
PubMed: 38590637
DOI: 10.3389/fphar.2024.1352842 -
Circulation Jun 2024Sodium-glucose cotransporter-2 inhibitors (SGLT2i) consistently improve heart failure and kidney-related outcomes; however, effects on major adverse cardiovascular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) consistently improve heart failure and kidney-related outcomes; however, effects on major adverse cardiovascular events (MACE) across different patient populations are less clear.
METHODS
This was a collaborative trial-level meta-analysis from the SGLT2i Meta-analysis Cardio-Renal Trialists Consortium, which includes all phase 3, placebo-controlled, outcomes trials of SGLT2i across 3 patient populations (patients with diabetes at high risk for atherosclerotic cardiovascular disease, heart failure [HF], or chronic kidney disease). The outcomes of interest were MACE (composite of cardiovascular death, myocardial infarction , or stroke), individual components of MACE (inclusive of fatal and nonfatal events), all-cause mortality, and death subtypes. Effect estimates for SGLT2i versus placebo were meta-analyzed across trials and examined across key subgroups (established atherosclerotic cardiovascular disease, previous myocardial infarction, diabetes, previous HF, albuminuria, chronic kidney disease stages, and risk groups).
RESULTS
A total of 78 607 patients across 11 trials were included: 42 568 (54.2%), 20 725 (26.4%), and 15 314 (19.5%) were included from trials of patients with diabetes at high risk for atherosclerotic cardiovascular disease, HF, or chronic kidney disease, respectively. SGLT2i reduced the rate of MACE by 9% (hazard ration [HR], 0.91 [95% CI, 0.87-0.96], <0.0001) with a consistent effect across all 3 patient populations (=0%) and across all key subgroups. This effect was primarily driven by a reduction in cardiovascular death (HR, 0.86 [95% CI, 0.81-0.92], <0.0001), with no significant effect for myocardial infarction in the overall population (HR, 0.95 [95% CI, 0.87-1.04], =0.29), and no effect on stroke (HR, 0.99 [95% CI, 0.91-1.07], =0.77). The benefit for cardiovascular death was driven primarily by reductions in HF death and sudden cardiac death (HR, 0.68 [95% CI, 0.46-1.02] and HR, 0.86 [95% CI, 0.78-0.95], respectively) and was generally consistent across subgroups, with the possible exception of being more apparent in those with albuminuria (=0.02).
CONCLUSIONS
SGLT2i reduce the risk of MACE across a broad range of patients irrespective of atherosclerotic cardiovascular disease, diabetes, kidney function, or other major clinical characteristics at baseline. This effect is driven primarily by a reduction of cardiovascular death, particularly HF death and sudden cardiac death, without a significant effect on myocardial infarction in the overall population, and no effect on stroke. These data may help inform selection for SGLT2i therapies across the spectrum of cardiovascular-kidney-metabolic disease.
Topics: Sodium-Glucose Transporter 2 Inhibitors; Humans; Cardiovascular Diseases; Renal Insufficiency, Chronic; Diabetes Mellitus, Type 2; Female; Male; Treatment Outcome; Aged
PubMed: 38583093
DOI: 10.1161/CIRCULATIONAHA.124.069568 -
Physiological Reports Apr 2024Chronic kidney disease (CKD) is characterized by an elevated risk for cerebrovascular disease including stroke. One mechanism that may contribute to this heightened risk...
Chronic kidney disease (CKD) is characterized by an elevated risk for cerebrovascular disease including stroke. One mechanism that may contribute to this heightened risk is an impairment in cerebrovascular carbon dioxide reactivity (CVR). We compared CVR between CKD patients stages III-IV and controls (CON) without CKD but matched for hypertension and diabetes status. CVR was measured via 5% CO inhalation followed by voluntary hyperventilation in 14 CKD and 11 CON participants while mean arterial pressure, end-tidal carbon dioxide, and middle cerebral artery blood velocity (MCAv) were measured continuously. CVR was quantified as the linear relationship between etCO and MCAv. We observed no difference in CVR between groups. Hypercapnic CVR: CKD = 1.2 ± 0.9 cm/s/mm Hg, CON = 1.3 ± 0.8 cm/s/mm Hg, hypocapnic CVR: CKD = 1.3 ± 0.9 cm/s/mm Hg, CON = 1.5 ± 0.7 cm/s/mm Hg, integrated CVR: CKD = 1.5 ± 1.1 cm/s/mm Hg, CON = 1.7 ± 0.8 cm/s/mm Hg, p ≥ 0.48. Unexpectedly, CVR was inversely related to estimated glomerular filtration rate in CKD (R = 0.37, p = 0.02). We report that CVR remains intact in CKD and is inversely related to eGFR. These findings suggest that other mechanisms beyond CVR contribute to the elevated stroke risk observed in CKD.
Topics: Humans; Carbon Dioxide; Blood Flow Velocity; Cerebrovascular Circulation; Stroke; Renal Insufficiency, Chronic
PubMed: 38570312
DOI: 10.14814/phy2.15998 -
Frontiers in Oncology 2024Anesthetic management of patients with renal cell carcinoma with tumor thrombus in the inferior vena cava (IVC) is challenging. This paper reports the experience of...
Anesthetic management of patients with renal cell carcinoma with tumor thrombus in the inferior vena cava (IVC) is challenging. This paper reports the experience of anesthesia management in a patient with advanced renal cell carcinoma with thrombus accumulation in the IVC, right atrium, and pulmonary artery who underwent radical nephrectomy and tumor thrombus removal assisted by cardiopulmonary bypass. The emboli, measuring approximately 3 × 6 cm in the left inferior pulmonary artery and 4 × 13 cm in the right main pulmonary artery, were removed completely. During incision of the IVC under systemic heparinization, significant blood loss occurred in the surgical field. The surgery took 724 min, and cardiopulmonary bypass took 396 min. Intraoperative blood loss was 22,000 ml. The patient was extubated 39 hours after surgery and stayed in intensive care unit for 3 days. At 1 year follow-up, the patient was in good health and leading a normal life.
PubMed: 38562176
DOI: 10.3389/fonc.2024.1372625 -
Frontiers in Immunology 2024Activation of complement through the alternative pathway (AP) has a key role in the pathogenesis of IgA nephropathy (IgAN). We previously showed, by intraperitoneal...
INTRODUCTION
Activation of complement through the alternative pathway (AP) has a key role in the pathogenesis of IgA nephropathy (IgAN). We previously showed, by intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE), C57BL/6 mice develop mild kidney damage in association with glomerular IgA deposition. To further address complement activity in causing glomerular histological alterations as suggested in the pathogenesis of IgAN, here we used mice with factor H mutation (FH) to render AP overactivation in conjunction with LCWE injection to stimulate intestinal production of IgA.
METHODS
Dose response to LCWE were examined between two groups of FH mice. Wild type (FH) mice stimulated with LCWE were used as model control.
RESULTS
The FH mice primed with high dose LCWE showed elevated IgA and IgA-IgG complex levels in serum. In addition to 100% positive rate of IgA and C3, they display elevated biomarkers of kidney dysfunction, coincided with severe pathological lesions, resembling those of IgAN. As compared to wild type controls stimulated by the same high dose LCWE, these FH mice exhibited stronger complement activation in the kidney and in circulation.
DISCUSSION
The new mouse model shares many disease features with IgAN. The severity of glomerular lesions and the decline of kidney functions are further aggravated through complement overactivation. The model may be a useful tool for preclinical evaluation of treatment response to complement-inhibitors.
Topics: Mice; Animals; Complement Factor H; Lacticaseibacillus casei; Mice, Inbred C57BL; Glomerulonephritis, IGA; Complement System Proteins; Immunoglobulin A; Mutation
PubMed: 38558821
DOI: 10.3389/fimmu.2024.1368322 -
Frontiers in Immunology 2024T follicular (TFH) and peripheral helper (TPH) cells have been increasingly recognized as a pathogenic subset of CD4 T cells in systemic lupus erythematosus (SLE). The...
INTRODUCTION
T follicular (TFH) and peripheral helper (TPH) cells have been increasingly recognized as a pathogenic subset of CD4 T cells in systemic lupus erythematosus (SLE). The SLAM Associated Protein (SAP) regulates TFH and TPH function by binding to the co-stimulatory signaling lymphocyte activation molecule family (SLAMF) receptors that mediate T cell - B cell interactions. SAP and SLAMF are critical for TPH-dependent B cell maturation into autoantibody-producing plasma cells that characterize SLE pathogenesis. We hypothesized that SAP-expressing TPH cells are involved in the pathogenesis of lupus nephritis (LN).
METHODS
Peripheral blood mononuclear cells (PBMC) were isolated using density gradient separation from whole blood. Cells were stained for cell surface markers, followed by permeabilization and staining of intracellular SAP for spectral flow cytometry analysis. We also analyzed SAP expression from renal infiltrating LN T cells using the available single-cell RNA sequencing (scRNA seq) Accelerated Medicines Partnership (AMP) SLE dataset.
RESULTS
PBMC from 30 patients with SLE (34 ± 10 years old, 83% female), including 10 patients with LN, were analyzed. We found an increase in total SAP-positive CD4 and CD8 T cells in SLE compared with controls (55.5 ± 2.6 vs. 41.3 ± 3.4, p=0.007, and 52.5 ± 3.0 vs. 39.2 ± 2.8, p=0.007 respectively). In CD4 T cells, the highest SAP expression was in the TPH subset. The frequency of SAPTPH in circulation correlated with disease activity; SLE patients with renal disease had higher levels of circulating SAPTPH that remained significant after adjusting for age, sex, race, low complements, and elevated anti-dsDNA (p=0.014). scRNA-seq data of renal infiltrating T cells in LN identified SAP expression to localize to the TFH-like CD4 cluster and GZMK+ CD8 cluster. Increased SAP expression in LN was associated with the differential expression of SLAMF3 and SLAMF7 and granzyme K and EOMES. The existence of two predominant SAP-expressing subsets, the TFH-like CD4 T cells, and GZMK+ effector CD8 T cells, was verified using scRNA-seq data from a human transcriptomic atlas of fifteen major organs.
CONCLUSION
The expansion of SAP-expressing T helper cells was associated with LN in our cohort and verified using scRNA-seq data of renal infiltrating T cells. Improved SLAM and SAP signaling understanding can identify new therapeutic targets in LN.
Topics: Humans; Female; Young Adult; Adult; Male; Lupus Nephritis; Leukocytes, Mononuclear; Signaling Lymphocytic Activation Molecule Associated Protein; Lupus Erythematosus, Systemic; T-Lymphocytes, Helper-Inducer
PubMed: 38550577
DOI: 10.3389/fimmu.2024.1327437