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Cardiovascular Diabetology May 2024Use of sodium-glucose-cotransporter-2 (SGLT2) inhibitors often causes an initial decline in glomerular filtration rate (GFR). This study addresses the question whether... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Use of sodium-glucose-cotransporter-2 (SGLT2) inhibitors often causes an initial decline in glomerular filtration rate (GFR). This study addresses the question whether the initial decline of renal function with SGLT2 inhibitor treatment is related to vascular changes in the systemic circulation.
METHODS
We measured GFR (mGFR) and estimated GFR (eGFR) in 65 patients with type 2 diabetes (T2D) at baseline and after 12 weeks of treatment randomized either to a combination of empagliflozin and linagliptin (SGLT2 inhibitor based treatment group) (n = 34) or metformin and insulin (non-SGLT2 inhibitor based treatment group) (n = 31). mGFR was measured using the gold standard clearance technique by constant infusion of inulin. In addition to blood pressure (BP), we measured pulse wave velocity (PWV) under standardized conditions reflecting vascular compliance of large arteries, as PWV is considered to be one of the most reliable vascular parameter of cardiovascular (CV) prognosis.
RESULTS
Both mGFR and eGFR decreased significantly after initiating treatment, but no correlation was found between change in mGFR and change in eGFR in either treatment group (SGLT2 inhibitor based treatment group: r=-0.148, p = 0.404; non-SGLT2 inhibitor based treatment group: r = 0.138, p = 0.460). Noticeably, change in mGFR correlated with change in PWV (r = 0.476, p = 0.005) in the SGLT2 inhibitor based treatment group only and remained significant after adjustment for the change in systolic BP and the change in heart rate (r = 0.422, p = 0.018). No such correlation was observed between the change in eGFR and the change in PWV in either treatment group.
CONCLUSIONS
Our main finding is that after initiating a SGLT2 inhibitor based therapy an exaggerated decline in mGFR was related with improved vascular compliance of large arteries reflecting the pharmacologic effects of SGLT2 inhibitor in the renal and systemic vascular bed. Second, in a single patient with T2D, eGFR may not be an appropriate parameter to assess the true change of renal function after receiving SGLT2 inhibitor based therapy.
TRIAL REGISTRATION
clinicaltrials.gov (NCT02752113).
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Glomerular Filtration Rate; Male; Diabetes Mellitus, Type 2; Middle Aged; Female; Benzhydryl Compounds; Aged; Treatment Outcome; Kidney; Glucosides; Time Factors; Linagliptin; Pulse Wave Analysis; Metformin; Insulin; Diabetic Nephropathies; Vascular Stiffness; Drug Therapy, Combination; Hypoglycemic Agents; Biomarkers; Clinical Relevance; Sodium-Glucose Transporter 2
PubMed: 38811998
DOI: 10.1186/s12933-024-02223-0 -
BMC Women's Health May 2024Perioperative urinary tract infections (PUTIs) are common in the United States and are a significant contributor to high healthcare costs. There is a lack of large...
INTRODUCTION
Perioperative urinary tract infections (PUTIs) are common in the United States and are a significant contributor to high healthcare costs. There is a lack of large studies on the risk factors for PUTIs after total hysterectomy (TH).
METHODS
We conducted a retrospective study using a national inpatient sample (NIS) of 445,380 patients from 2010 to 2019 to analyze the risk factors and annual incidence of PUTIs associated with TH perioperatively.
RESULTS
PUTIs were found in 9087 patients overall, showing a 2.0% incidence. There were substantial differences in the incidence of PUTIs based on age group (P < 0.001). Between the two groups, there was consistently a significant difference in the type of insurance, hospital location, hospital bed size, and hospital type (P < 0.001). Patients with PUTIs exhibited a significantly higher number of comorbidities (P < 0.001). Unsurprisingly, patients with PUTIs had a longer median length of stay (5 days vs. 2 days; P < 0.001) and a higher in-hospital death rate (from 0.1 to 1.1%; P < 0.001). Thus, the overall hospitalization expenditures increased by $27,500 in the median ($60,426 vs. $32,926, P < 0.001) as PUTIs increased medical costs. Elective hospitalizations are less common in patients with PUTIs (66.8% vs. 87.6%; P < 0.001). According to multivariate logistic regression study, the following were risk variables for PUTIs following TH: over 45 years old; number of comorbidities (≥ 1); bed size of hospital (medium, large); teaching hospital; region of hospital(south, west); preoperative comorbidities (alcohol abuse, deficiency anemia, chronic blood loss anemia, congestive heart failure, diabetes, drug abuse, hypertension, hypothyroidism, lymphoma, fluid and electrolyte disorders, metastatic cancer, other neurological disorders, paralysis, peripheral vascular disorders, psychoses, pulmonary circulation disorders, renal failure, solid tumor without metastasis, valvular disease, weight loss); and complications (sepsis, acute myocardial infarction, deep vein thrombosis, gastrointestinal hemorrhage, pneumonia, stroke, wound infection, wound rupture, hemorrhage, pulmonary embolism, blood transfusion, postoperative delirium).
CONCLUSIONS
The findings suggest that identifying these risk factors can lead to improved preventive strategies and management of PUTIs in TH patients. Counseling should be done prior to surgery to reduce the incidence of PUTIs.
THE MANUSCRIPT ADDS TO CURRENT KNOWLEDGE
In medical practice, the identification of risk factors can lead to improved patient prevention and treatment strategies. We conducted a retrospective study using a national inpatient sample (NIS) of 445,380 patients from 2010 to 2019 to analyze the risk factors and annual incidence of PUTIs associated with TH perioperatively. PUTIs were found in 9087 patients overall, showing a 2.0% incidence. We found that noted increased length of hospital stay, medical cost, number of pre-existing comorbidities, size of the hospital, teaching hospitals, and region to also a play a role in the risk of UTI's.
CLINICAL TOPICS
Urogynecology.
Topics: Humans; Female; Retrospective Studies; Urinary Tract Infections; Hysterectomy; Risk Factors; Middle Aged; Incidence; Adult; Postoperative Complications; United States; Aged; Length of Stay; Perioperative Period
PubMed: 38811924
DOI: 10.1186/s12905-024-03153-5 -
Pharmaceutics Apr 2024Plasminogen activators, such as recombinant tissue-type plasminogen activators (rtPAs), while effective in treating thromboembolic diseases, often induce hemorrhagic...
Plasminogen activators, such as recombinant tissue-type plasminogen activators (rtPAs), while effective in treating thromboembolic diseases, often induce hemorrhagic complications due to non-specific enzyme activities in the systemic circulation. This study evaluated the targeting efficiency, efficacy, biodistribution, and potential toxicity of a rtPA covalently attached to chitosan-coated magnetic nanoparticles (chitosan-MNP-rtPA). The thrombolytic activity of a chitosan-MNP-rtPA was preserved by protection from an endogenous plasminogen activator inhibitor-1 (PAI-1) in whole blood and after circulation in vivo, as examined by thromboelastometry. Single-photon emission computed tomography (SPECT) demonstrated real-time retention of a Tc-MNP-rtPA induced by magnet application in a rat embolic model; an 80% reduction in rtPA dosage for a chitosan-MNP-rtPA with magnetic guidance was shown to restore blood flow. After treatment, iron deposition was observed in the reticuloendothelial systems, with portal edema and neutrophil infiltration in the liver at a ten-fold higher dose but not the regular dose. Nevertheless, no liver or renal toxicity was observed at this higher dose. In conclusion, the liver may still be the major deposit site of rtPA nanocomposites after targeted delivery; chitosan-coated MNPs are potentially amenable to target therapeutics with parenteral administration.
PubMed: 38794257
DOI: 10.3390/pharmaceutics16050596 -
Children (Basel, Switzerland) May 2024In neonates with acute lung injury (ALI), targeting lower oxygenation saturations is suggested to limit oxygen toxicity while maintaining vital organ function. Although...
In neonates with acute lung injury (ALI), targeting lower oxygenation saturations is suggested to limit oxygen toxicity while maintaining vital organ function. Although thresholds for cerebral autoregulation are studied for the management of premature infants, the impact of hypoxia on hemodynamics, tissue oxygen consumption and extraction is not well understood in term infants with ALI. We examined hemodynamics, cerebral autoregulation and fractional oxygen extraction, as measured by near-infrared spectroscopy (NIRS) and blood gases, in a neonatal porcine oleic acid injury model of moderate ALI. We hypothesized that in ALI animals, cerebral oxygen extraction would be increased to a greater degree than kidney or gut oxygen extraction as indicative of the brain's adaptive efforts to increase cerebral oxygen extraction at the expense of splanchnic end organs. Fifteen anesthetized, ventilated 5-day-old neonatal piglets were divided into moderate lung injury by treatment with oleic acid or control (sham injection). The degree of lung injury was quantified at baseline and after establishment of ALI by blood gases, ventilation parameters and calculated oxygenation deficit, hemodynamic indices by echocardiography and lung injury score by ultrasound. PaCO was maintained constant during ventilation. Cerebral, renal and gut oxygenation was determined by NIRS during stepwise decreases in inspired oxygen from 50% to 21%, correlated with PaO and PvO; changes in fractional oxygen extraction (ΔFOE) were calculated from NIRS and from regional blood gas samples. The proportion of cerebral autoregulation impairment attributable to blood pressure, and to hypoxemia, was calculated from autoregulation nomograms. ALI manifested as hypoxemia with increasing intrapulmonary shunt fraction, decreased lung compliance and increased resistance, and marked increase in lung ultrasound score. Brain, gut and renal NIRS, obtained from probes placed over the anterior skull, central abdomen and flank, respectively, correlated with concurrent SVC (brain) or IVC (gut, renal) PvO and SvO. Cerebral autoregulation was impaired after ALI as a function of blood pressure at all FiO steps, but predominantly by hypoxemia at FiO < 40%. Cerebral ΔFOE was higher in ALI animals at all FiO steps. We conclude that in an animal model of neonatal ALI, cerebrovascular blood flow regulation is primarily dependent on oxygenation. There is not a defined oxygenation threshold below which cerebral autoregulation is impaired in ALI. Cerebral oxygen extraction is enhanced in ALI, reflecting compensation for exhausted cerebral autoregulation due to the degree of hypoxemia and/or hypotension, thereby protecting against tissue hypoxia.
PubMed: 38790606
DOI: 10.3390/children11050611 -
The Egyptian Heart Journal : (EHJ) :... May 2024Perforation by pacemaker leads, although rare, is a complication reported since the introduction of pacemaker therapy. Although historically reported frequencies were as...
BACKGROUND
Perforation by pacemaker leads, although rare, is a complication reported since the introduction of pacemaker therapy. Although historically reported frequencies were as high as 5%, recent reports have cited frequencies ranging from 1 to 2%. We report a case where a screw-type atrial lead slightly penetrated the right atrial wall, causing chronic abrasion of the ascending aorta, resulting in shock.
CASE PRESENTATION
A 54-year-old male presented with dilated cardiomyopathy diagnosed at 40 years of age when he developed decompensated heart failure. Despite ongoing treatment, his heart failure worsened, leading to hospitalization at the age of 54. During his hospital stay, he experienced cardiac arrest that required cardiopulmonary resuscitation, followed by a return of spontaneous circulation. He was subsequently transferred to our institution after initiation of venoarterial extracorporeal membrane oxygenation (VA-ECMO) and an intra-aortic balloon pump (IABP). Echocardiography revealed an ejection fraction of 25%, left ventricular end-diastolic diameter of 60 mm, and severe mitral regurgitation (MR). Transcatheter mitral valve repair was performed to treat severe MR, followed by implantation of a cardiac resynchronization therapy defibrillator (CRT-D). Three months later, the patient was brought to our emergency department by ambulance because of hypotension. Contrast-enhanced computed tomography revealed pericardial effusion causing cardiac tamponade, necessitating emergency pericardial decompression via left fourth intercostal mini-thoracotomy and drain placement. Upon transfer to the intensive care unit, 1200 mL of blood was drained from the chest tube, prompting a return to the operating room for a median sternotomy. It was discovered that the pacemaker lead on the left side of the right atrium had slowly eroded into the aorta, leading to perforation. The ascending aorta was repaired and hemostasis was achieved; the patient recovered uneventfully and was discharged on postoperative day 18.
CONCLUSIONS
The pacemaker lead perforated the right atrium; chronic abrasion of the lead against the ascending aorta resulted in bleeding from the ascending aorta 3 months later.
PubMed: 38789703
DOI: 10.1186/s43044-024-00494-2 -
Scientific Reports May 2024Natriuretic peptides (NPs) are cardio-derived hormones that have a crucial role in maintaining cardiovascular homeostasis. Physiological effects of NPs are mediated by...
Natriuretic peptides (NPs) are cardio-derived hormones that have a crucial role in maintaining cardiovascular homeostasis. Physiological effects of NPs are mediated by binding to natriuretic peptide receptors 1 and 2 (NPR1/2), whereas natriuretic peptide receptor 3 (NPR3) acts as a clearance receptor that removes NPs from the circulation. Mouse studies have shown that local NP-signaling in the kidney glomerulus is important for the maintenance of renal homeostasis. In this study we examined the expression of NPR3 in kidney tissue and explored its involvement in renal physiology and disease by generating podocyte-specific knockout mice (NPR3) as well as by using an NPR3 inhibitor (NPR3i) in rodent models of kidney disease. NPR3 was highly expressed by podocytes. NPR3 animals showed no renal abnormalities under healthy conditions and responded similarly to nephrotoxic serum (NTS) induced glomerular injury. However, NPR3i showed reno-protective effects in the NTS-induced model evidenced by decreased glomerulosclerosis and reduced podocyte loss. In a ZSF1 rat model of diabetic kidney injury, therapy alone with NPR3i did not have beneficial effects on renal function/histology, but when combined with losartan (angiotensin receptor blocker), NPR3i potentiated its ameliorative effects on albuminuria. In conclusion, these results suggest that NPR3 may contribute to kidney disease progression.
Topics: Animals; Receptors, Atrial Natriuretic Factor; Mice; Mice, Knockout; Podocytes; Rats; Kidney Glomerulus; Male; Disease Models, Animal; Kidney Diseases; Losartan; Diabetic Nephropathies
PubMed: 38782980
DOI: 10.1038/s41598-024-61603-4 -
Annals of Gastroenterology 2024Small intestinal bacterial overgrowth (SIBO) occurs frequently in patients with cirrhosis, particularly in those with ascites, and promotes the translocation of...
BACKGROUND
Small intestinal bacterial overgrowth (SIBO) occurs frequently in patients with cirrhosis, particularly in those with ascites, and promotes the translocation of gut-derived bacterial products into the portal and systemic circulation. We investigated the effects of SIBO on systemic inflammatory activity, circulatory and renal function, and the degree of liver fibrosis in patients with cirrhosis and ascites.
METHODS
Eighty patients with cirrhosis and ascites were prospectively enrolled. SIBO was determined by lactulose breath test. Serum levels of lipopolysaccharide-binding protein (LBP), tumor necrosis factor-α, and interleukin-6, mean arterial pressure (MAP), cardiac output (CO) by echocardiography, systemic vascular resistance (SVR) as MAP/CO ratio, plasma renin activity (PRA), plasma aldosterone, radioisotope-assessed glomerular filtration rate (GFR), and liver stiffness by shear wave elastography were evaluated.
RESULTS
SIBO was detected in 58 patients (72.5%). Compared to patients without SIBO, those diagnosed with SIBO had significantly higher LBP levels (P<0.001), significantly lower MAP (P<0.001) and SVR (P<0.001), and significantly higher CO (P=0.002) and PRA (P<0.001). Patients with SIBO had significantly lower GFR (P=0.02) and higher liver stiffness (P=0.04) compared to those without SIBO. The presence of SIBO was independently associated with LBP (P=0.007) and PRA (P=0.01). Among patients with SIBO, peak breath hydrogen concentration was significantly correlated with serum LBP (P<0.001), MAP (P<0.001), CO (P=0.008), SVR (P=0.001), PRA (P=0.005), plasma aldosterone (P<0.001), GFR (P<0.001), and liver stiffness (P=0.004).
CONCLUSION
SIBO in patients with cirrhosis and ascites may predispose to greater systemic inflammation, circulatory and renal dysfunction, and more advanced liver fibrosis.
PubMed: 38779647
DOI: 10.20524/aog.2024.0881 -
Experimental and Clinical... Apr 2024This brief overview is designed to address the options for increasing organ transplant rates to between 100 and 120 transplanted organs per million population globally.... (Review)
Review
This brief overview is designed to address the options for increasing organ transplant rates to between 100 and 120 transplanted organs per million population globally. The focus of this review is the data produced through the World Health Organization's Global Observatory on Donation and Transplantation, with consideration for the issues that different countries need to address to achieve higher transplant rates. Without both optimized living donation and optimized deceased donation, rates of transplant are not sufficient to provide for a level of self-dependency for transplant therapy. Deceased donation comprises both donation from donors declared dead after cessation of all functions of the brain and donors declared dead from irreversible cessation of circulation of the blood. The preservation strategies that hold the greatest chance of increasing the utility of marginal and older donors involve normothermic circulation to prevent ischemic damage and potentially restore function of damaged organs. Normothermic in situ perfusion of abdominal organs has demonstrated utility, and consideration must be given to normothermic perfusion of the thoracic organs to improve heart and lung transplants, but this may challenge the legal definitions of death. Each nation must endeavor to increase organ donation capacity across the spectrum of donor types and must address the opportunities that normothermic perfusion of organs at retrieval may offer to alleviate shortages of organs for transplant and provide selfdependency for the communities.
Topics: Humans; Organ Transplantation; Tissue Donors; Tissue and Organ Procurement; Organ Preservation; Health Services Accessibility; Donor Selection; Risk Factors
PubMed: 38775691
DOI: 10.6002/ect.BDCDSymp.L3 -
EMBO Reports May 2024Vitamin A (retinol) is distributed via the blood bound to its specific carrier protein, retinol-binding protein 4 (RBP4). Retinol-loaded RBP4 is secreted into the...
Vitamin A (retinol) is distributed via the blood bound to its specific carrier protein, retinol-binding protein 4 (RBP4). Retinol-loaded RBP4 is secreted into the circulation exclusively from hepatocytes, thereby mobilizing hepatic retinoid stores that represent the major vitamin A reserves in the body. The relevance of extrahepatic retinoid stores for circulating retinol and RBP4 levels that are usually kept within narrow physiological limits is unknown. Here, we show that fasting affects retinoid mobilization in a tissue-specific manner, and that hormone-sensitive lipase (HSL) in adipose tissue is required to maintain serum concentrations of retinol and RBP4 during fasting in mice. We found that extracellular retinol-free apo-RBP4 induces retinol release by adipocytes in an HSL-dependent manner. Consistently, global or adipocyte-specific HSL deficiency leads to an accumulation of retinoids in adipose tissue and a drop of serum retinol and RBP4 during fasting, which affects retinoid-responsive gene expression in eye and kidney and lowers renal retinoid content. These findings establish a novel crosstalk between liver and adipose tissue retinoid stores for the maintenance of systemic vitamin A homeostasis during fasting.
PubMed: 38769419
DOI: 10.1038/s44319-024-00158-x -
Frontiers in Nutrition 2024The French maritime pine bark extract Pycnogenol is a proprietary product from Aiton. It complies with the quality specifications in the monograph "Pine extract" in... (Review)
Review
The French maritime pine bark extract Pycnogenol is a proprietary product from Aiton. It complies with the quality specifications in the monograph "Pine extract" in the section of dietary supplements. Pycnogenol is standardized to contain 65-75% procyanidins which are a variety of biopolymers consisting of catechin and epicatechin monomeric units. The effects of Pycnogenol have been researched in a multitude of human studies. The basis for any activity is the bioavailability of constituents and metabolites of the extract. General principles of compound absorption, distribution, metabolism and elimination as well as specific data from studies with Pycnogenol are summarized and discussed in this review. Based on plasma concentration profiles it can be concluded that low molecular weight constituents of the extract, such as catechin, caffeic and ferulic acid, taxifolin are readily absorbed from the small intestine into systemic circulation. Procyanidin oligomers and polymers are subjected to gut microbial degradation in the large intestine yielding small bioavailable metabolites such as 5-(3',4'-dihydroxyphenyl)-γ-valerolactone. After intake of Pycnogenol, constituents and metabolites have been also detected in blood cells, synovial fluid and saliva indicating a substantial distribution in compartments other than serum. In studies simultaneously investigating concentrations in different specimen, a preferential distribution of individual compounds has been observed, e.g., of ferulic acid and 5-(3',4'-dihydroxyphenyl)-γ-valerolactone into synovial fluid compared to serum. The main route of elimination of constituents and metabolites of the French pine bark extract is the renal excretion. The broad knowledge accumulated regarding the pharmacokinetics of compounds and metabolites of Pycnogenol constitute a rational basis for effects characterized on a cellular level and observed in human clinical studies.
PubMed: 38757126
DOI: 10.3389/fnut.2024.1389422