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Circulation Apr 2019Glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as 2 new classes of antihyperglycemic agents that... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus.
BACKGROUND
Glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as 2 new classes of antihyperglycemic agents that also reduce cardiovascular risk. The relative benefits in patients with and without established atherosclerotic cardiovascular disease for different outcomes with these classes of drugs remain undefined.
METHODS
We performed a systematic review and trial-level meta-analysis of GLP1-RA and SGLT2i cardiovascular outcomes trials using the PubMed and EMBASE databases (Excerpta Medica Database). The primary outcomes were the composite of myocardial infarction, stroke, and cardiovascular death (MACE); hospitalization for heart failure; and progression of kidney disease.
RESULTS
In total, data from 8 trials and 77 242 patients, 42 920 (55.6%) in GLP1-RA trials, and 34 322 (44.4%) in SGLT2i trials, were included. Both drug classes reduced MACE in a similar magnitude with GLP1-RA reducing the risk by 12% (hazard ratio [HR], 0.88; 95% CI, 0.84-0.94; P<0.001) and SGLT2i by 11% (HR, 0.89; 95% CI, 0.83-0.96; P=0.001). For both drug classes, this treatment effect was restricted to a 14% reduction in those with established atherosclerotic cardiovascular disease (HR, 0.86; 95% CI, 0.80-0.93; P=0.002), whereas no effect was seen in patients without established atherosclerotic cardiovascular disease (HR, 1.01; 95% CI, 0.87-1.19; P=0.81; P interaction, 0.028). SGLT2i reduced hospitalization for heart failure by 31% (HR, 0.69; 95% CI, 0.61-0.79; P<0.001), whereas GLP1-RA did not have a significant effect (HR, 0.93; 95% CI, 0.83-1.04; P=0.20). Both GLP1-RA (HR, 0.82; 95% CI, 0.75-0.89; P<0.001) and SGLT2i (HR, 0.62; 95% CI, 0.58-0.67; P<0.001) reduced the risk of progression of kidney disease including macroalbuminuria, but only SGLT2i reduced the risk of worsening estimated glomerular filtration rate, end-stage kidney disease, or renal death (HR, 0.55; 95% CI, 0.48-0.64; P<0.001).
CONCLUSIONS
In trials reported to date, GLP1-RA and SGLT2i reduce atherosclerotic MACE to a similar degree in patients with established atherosclerotic cardiovascular disease, whereas SGLT2i have a more marked effect on preventing hospitalization for heart failure and progression of kidney disease. Their distinct clinical benefit profiles should be considered in the decision-making process when treating patients with type 2 diabetes mellitus.
Topics: Aged; Atherosclerosis; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Diabetic Nephropathies; Female; Glucagon-Like Peptide Receptors; Humans; Hypoglycemic Agents; Kidney Diseases; Male; Middle Aged; Proportional Hazards Models; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 30786725
DOI: 10.1161/CIRCULATIONAHA.118.038868 -
Journal of Neurology Apr 2020Rhabdomyolysis (RML) is an interdisciplinary condition due to muscle cell injury followed by the release of cell components into circulation. Etiology of RML has a broad...
BACKGROUND
Rhabdomyolysis (RML) is an interdisciplinary condition due to muscle cell injury followed by the release of cell components into circulation. Etiology of RML has a broad range; a serious complication is acute kidney injury (AKI). Despite its high relevance, there is no established formal definition for RML.
OBJECTIVES
A systematic review, focusing on RML definition, providing a recommendation for clinicians.
METHOD
Systematic literature research in PubMed and Embase (1968-07/2018).
RESULTS
The database research presented 8136 articles in PubMed and 2151 in Embase. After screening, 614 papers were retained for statistical analysis. A retrospective study was the most used design (44%). A definition of RML was stated in 231 studies (37.6%), including a precise creatine kinase level (CK) cut-off most frequently (67.1%). In 53/231 (22.9%) studies the CK cut-off was > 5 × upper limit of normal (ULN), and in 64/231 (27.7%) studies > 1000 IU/L. Further components of definitions were elevated CK without specific thresholds, and clinical symptoms. Exclusion criteria referring to the definition of RML were established in 113 studies, including myocardial, renal, cerebral and neuromuscular characteristics.
CONCLUSION
At present, we recommend a clinical syndrome of acute muscle weakness, myalgia, and muscle swelling combined with a CK cut-off value of > 1000 IU/L/ or CK > 5 × ULN for the standard definition of a mild RML. Additionally measured myoglobinuria and AKI indicate a severe type of RML. Exclusion criteria as well as the chronological sequence need to be considered for a conclusive RML definition.
Topics: Acute Kidney Injury; Creatine Kinase; Humans; Muscle Weakness; Myalgia; Rhabdomyolysis; Syndrome
PubMed: 30617905
DOI: 10.1007/s00415-019-09185-4 -
Clinical Toxicology (Philadelphia, Pa.) Jun 2010Colchicine is used mainly for the treatment and prevention of gout and for familial Mediterranean fever (FMF). It has a narrow therapeutic index, with no clear-cut... (Review)
Review
INTRODUCTION
Colchicine is used mainly for the treatment and prevention of gout and for familial Mediterranean fever (FMF). It has a narrow therapeutic index, with no clear-cut distinction between nontoxic, toxic, and lethal doses, causing substantial confusion among clinicians. Although colchicine poisoning is sometimes intentional, unintentional toxicity is common and often associated with a poor outcome.
METHODS
We performed a systematic review by searching OVID MEDLINE between 1966 and January 2010. The search strategy included "colchicine" and "poisoning" or "overdose" or "toxicity" or "intoxication."
TOXICOKINETICS
Colchicine is readily absorbed after oral administration, but undergoes extensive first-pass metabolism. It is widely distributed and binds to intracellular elements. Colchicine is primarily metabolized by the liver, undergoes significant enterohepatic re-circulation, and is also excreted by the kidneys. THERAPEUTIC AND TOXIC DOSES: The usual adult oral doses for FMF is 1.2-2.4 mg/day; in acute gout 1.2 mg/day and for gout prophylaxis 0.5-0.6 mg/day three to four times a week. High fatality rate was reported after acute ingestions exceeding 0.5 mg/kg. The lowest reported lethal doses of oral colchicine are 7-26 mg.
DRUG INTERACTIONS
CYP 3A4 and P-glycoprotein inhibitors, such as clarithromycin, erythromycin, ketoconazole, ciclosporin, and natural grapefruit juice can increase colchicine concentrations. Co-administration with statins may increase the risk of myopathy.
MECHANISMS OF TOXICITY
Colchicine's toxicity is an extension of its mechanism of action - binding to tubulin and disrupting the microtubular network. As a result, affected cells experience impaired protein assembly, decreased endocytosis and exocytosis, altered cell morphology, decreased cellular motility, arrest of mitosis, and interrupted cardiac myocyte conduction and contractility. The culmination of these mechanisms leads to multi-organ dysfunction and failure. REPRODUCTIVE TOXICOLOGY AND LACTATION: Colchicine was not shown to adversely affect reproductive potential in males or females. It crosses the placenta but there is no evidence of fetal toxicity. Colchicine is excreted into breast milk and considered compatible with lactation.
CLINICAL FEATURES
Colchicine poisoning presents in three sequential and usually overlapping phases: 1) 10-24 h after ingestion - gastrointestinal phase mimicking gastroenteritis may be absent after intravenous administration; 2) 24 h to 7 days after ingestion - multi-organ dysfunction. Death results from rapidly progressive multi-organ failure and sepsis. Delayed presentation, pre-existing renal or liver impairment are associated with poor prognosis. 3) Recovery typically occurs within a few weeks of ingestion, and is generally a complete recovery barring complications of the acute illness.
DIAGNOSIS
History of ingestion of tablets, parenteral administration, or consumption of colchicine-containing plants suggest the diagnosis. Colchicine poisoning should be suspected in patients with access to the drug and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis, and prerenal azotemia).
MANAGEMENT
Timely gastrointestinal decontamination should be considered with activated charcoal, and very large, recent (<60 min) ingestions may warrant gastric lavage. Supportive treatments including administration of granulocyte colony-stimulating factor are the mainstay of treatment. Although a specific experimental treatment (Fab fragment antibodies) for colchicine poisoning has been used, it is not commercially available.
CONCLUSION
Although colchicine poisoning is relatively uncommon, it is imperative to recognize its features as it is associated with a high mortality rate when missed.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Adult; Charcoal; Clarithromycin; Clinical Trials as Topic; Colchicine; Colony-Stimulating Factors; Drug Interactions; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Familial Mediterranean Fever; Female; Granulocyte Colony-Stimulating Factor; Humans; Male
PubMed: 20586571
DOI: 10.3109/15563650.2010.495348 -
Journal of Traditional Chinese Medicine... Jun 2023To evaluate the efficacy and safety of activating blood circulation and removing blood stasis in terms of Traditional Chinese Medicine (TCM) for managing renal fibrosis... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of activating blood circulation and removing blood stasis of Traditional Chinese Medicine for managing renal fibrosis in patients with chronic kidney disease: a systematic review and Meta-analysis.
OBJECTIVE
To evaluate the efficacy and safety of activating blood circulation and removing blood stasis in terms of Traditional Chinese Medicine (TCM) for managing renal fibrosis (RF) in patients with chronic kidney disease (CKD).
METHODS
We searched randomized controlled trials (RCTs) from eight databases.
RESULTS
Sixteen eligible studies with 1,356 participants were included in this study. Compared to treatment with Western Medicine (WM) alone, the combined treatment with activating blood circulation and removing blood stasis in terms of TCM (ARTCM) and WM to manage RF in patients with CKD significantly ameliorated type Ⅳ collagen (CⅣ) (: 2.17, 95% : 3.01 to 1.34), type Ⅲ procollagen (PCⅢ) (: 1.08, 95% : 1.64 to 0.53), laminin (LN) (: 1.28, 95% : 1.65 to 0.90), transforming growth factor β 1 (TGFβ1) (: 0.65, 95% : 1.18 to 0.12), serum creatinine (Scr) (: 1.36, 95% : 1.85 to 0.87), blood urea nitrogen (BUN) (: 1.51, 95% : 2.59 to 0.43), and 24 h urine protein (24hUpro) (: 1.23; 95% : 1.96 to 0.50). The level of hyaluronic acid (HA) was similar in both types of treatment (: 0.74, 95% : 1.91 to 0.44). The subgroup analysis showed that the duration of 8 weeks might affect the concentration of C-Ⅳ, PC-Ⅲ, and LN (<0.05). The effectiveness of the longer duration to C-Ⅳ, PC-Ⅲ, and LN was not certain. However, the result should be interpreted in care. The safety of the treatment using ARTCM and WM could not be evaluated because a few studies had reported adverse effects. The results of the Metaanalysis were not stable enough. There was publication bias for the reports on Scr ( 0.001), C-Ⅳ ( 0.001), PC-Ⅲ ( 0.026), and LN ( 0.030) and no publication bias for the reports on BUN ( 0.293). The quality of evidence varied from low to very low.
CONCLUSIONS
The combined treatment using ARTCM and WM to manage RF in patients with CKD has some advantages over treatment with WM alone. Highquality RCTs need to be conducted for the strong support.
Topics: Humans; Medicine, Chinese Traditional; Drugs, Chinese Herbal; Renal Insufficiency, Chronic; Phytotherapy; Fibrosis
PubMed: 37147744
DOI: 10.19852/j.cnki.jtcm.20230308.003 -
Surgical Endoscopy Feb 2007The precise physiologic consequences of insufflating carbon dioxide into the abdominal cavity during laparoscopy are not yet fully understood. This systematic review... (Review)
Review
BACKGROUND
The precise physiologic consequences of insufflating carbon dioxide into the abdominal cavity during laparoscopy are not yet fully understood. This systematic review aimed to investigate whether pneumoperitoneum results in decreased renal blood flow (RBF) or renal function.
METHODS
A literature search was conducted electronically using Medline, Embase, and the Cochrane libraries on 1 July 2005. Various combinations of the medical subject headings--renal blood flow, pneumoperitoneum, renal function, and laparoscopy--were searched in all three databases. Reference lists from articles fulfilling the search criteria were used to identify additional articles.
RESULTS
The literature search retrieved 20 articles concerning RBF and 25 articles concerning renal function during pneumoperitoneum. It was found that 17 of the 20 studies identified a decrease in RBF, and 20 of the 25 studies identified a decrease in renal function during pneumoperitoneum.
CONCLUSION
There appears to be sufficient evidence to conclude that both renal function and RBF are decreased during pneumoperitoneum. The magnitude of the decrease is dependent on factors such as preoperative renal function, level of hydration, level of pneumoperitoneum, patient positioning, and duration of pneumoperitoneum.
Topics: Animals; Case-Control Studies; Creatinine; Glomerular Filtration Rate; Humans; Kidney Function Tests; Laparoscopy; Pneumoperitoneum, Artificial; Reference Values; Renal Circulation; Risk Assessment
PubMed: 17160650
DOI: 10.1007/s00464-006-0250-x -
JTCVS Open Dec 2021A meta-analysis of randomized controlled trials was performed to compare the effects of miniaturized extracorporeal circulation (MECC) and conventional extracorporeal...
OBJECTIVE
A meta-analysis of randomized controlled trials was performed to compare the effects of miniaturized extracorporeal circulation (MECC) and conventional extracorporeal circulation (CECC) on morbidity and mortality rates after cardiac surgery.
METHODS
A comprehensive literature search was conducted using Ovid, PubMed, Medline, EMBASE, and the Cochrane databases. Randomized controlled trials from the year 2000 with n > 40 patients were considered. Key search terms included variations of "mini," "cardiopulmonary," "bypass," "extracorporeal," "perfusion," and "circuit." Studies were assessed for bias using the Cochrane Risk of Bias tool. The primary outcomes were postoperative mortality and stroke. Secondary outcomes included arrhythmia, myocardial infarction, renal failure, blood loss, and a composite outcome comprised of mortality, stroke, myocardial infarction and renal failure. Duration of intensive care unit, and hospital stay was also recorded.
RESULTS
The 42 studies eligible for this study included a total of 2154 patients who underwent CECC and 2196 patients who underwent MECC. There were no significant differences in any preoperative or demographic characteristics. Compared with CECC, MECC did not reduce the incidence of mortality, stroke, myocardial infarction, and renal failure but did significantly decrease the composite of these outcomes (odds ratio, 0.64; 95% confidence interval [CI], 0.50-0.81; = .0002). MECC was also associated with reductions in arrhythmia (odds ratio, 0.67; 95% CI, 0.54-0.83; = .0003), blood loss (mean difference [MD], -96.37 mL; 95% CI, -152.70 to -40.05 mL; = .0008), hospital stay (MD, -0.70 days; 95% CI, -1.21 to -0.20 days; = .006), and intensive care unit stay (MD, -2.27 hours; 95% CI, -3.03 to -1.50 hours; < .001).
CONCLUSIONS
MECC demonstrates clinical benefits compared with CECC. Further studies are required to perform a cost-utility analysis and to assess the long-term outcomes of MECC. These should use standardized definitions of endpoints such as mortality and renal failure to reduce inconsistency in outcome reporting.
PubMed: 36004169
DOI: 10.1016/j.xjon.2021.09.037 -
Frontiers in Cardiovascular Medicine 2022Patients with a Fontan circulation are at risk for sequelae of Fontan physiology during follow-up. Fontan physiology affects all organ systems and an overview of...
INTRODUCTION
Patients with a Fontan circulation are at risk for sequelae of Fontan physiology during follow-up. Fontan physiology affects all organ systems and an overview of end-organ damage is needed.
METHODS
We performed a systematic review of abnormalities in multiple organ systems for patients with a longstanding Fontan circulation. We searched online databases for articles describing abnormalities in multiple organ systems. Cardio-pulmonary abnormalities, protein losing enteropathy, and Fontan associated liver disease have already extensively been described and were excluded from this systematic review.
RESULTS
Our search returned 5,704 unique articles. After screening, we found 111 articles relating to multiple organ systems. We found abnormalities in, among others, the nervous system, pituitary, kidneys, and musculoskeletal system. Pituitary edema-relating to the unique pituitary vasculature- may affect the thyroid axis. Renal dysfunction is common. Creatinine based renal function estimates may be inappropriate due to myopenia. Both lean muscle mass and bone mineral density are decreased. These abnormalities in multiple organ systems may be related to Fontan physiology, cyanosis, iatrogenic factors, or lifestyle.
CONCLUSIONS
Health care providers should be vigilant for hypothyroidism, visual or hearing deficits, and sleep disordered breathing in Fontan patients. We recommend including cystatin C for assessment of renal function. This review may aid health care providers and guide future research. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021232461, PROSPERO, identifier: CRD42021232461.
PubMed: 35391839
DOI: 10.3389/fcvm.2022.826096 -
Magma (New York, N.Y.) Feb 2020Phase-contrast magnetic resonance imaging (PC-MRI) is a non-invasive method used to compute blood flow velocity and volume. This systematic review aims to discuss the...
OBJECTIVE
Phase-contrast magnetic resonance imaging (PC-MRI) is a non-invasive method used to compute blood flow velocity and volume. This systematic review aims to discuss the current status of renal PC-MRI and provide practical recommendations which could inform future clinical studies and its adoption in clinical practice.
METHODOLOGY
A comprehensive search of all the PC-MRI studies in human healthy subjects or patients related to the kidneys was performed.
RESULTS
A total of 39 studies were included in which PC-MRI was used to measure renal blood flow (RBF) alongside other derivative hemodynamic parameters. PC-MRI generally showed good correlation with gold standard methods of RBF measurement, both in vitro and in vivo, and good reproducibility. Despite PC-MRI not being routinely used in clinical practice, there are several clinical studies showing its potential to support diagnosis and monitoring of renal diseases, in particular renovascular disease, chronic kidney disease and autosomal dominant polycystic kidney disease.
DISCUSSION
Renal PC-MRI shows promise as a non-invasive technique to reliably measure RBF, both in healthy volunteers and in patients with renal disease. Future multicentric studies are needed to provide definitive normative ranges and to demonstrate the clinical potential of PC-MRI, likely as part of a multi-parametric renal MRI protocol.
Topics: Adult; Aged; Blood Flow Velocity; Contrast Media; Female; Healthy Volunteers; Humans; Kidney; Magnetic Resonance Imaging; Male; Middle Aged; Perfusion; Polycystic Kidney Diseases; Renal Artery Obstruction; Renal Circulation; Reproducibility of Results
PubMed: 31422518
DOI: 10.1007/s10334-019-00772-0 -
Nephrology, Dialysis, Transplantation :... Sep 2018Renal perfusion provides the driving pressure for glomerular filtration and delivers the oxygen and nutrients to fuel solute reabsorption. Renal ischaemia is a major...
Renal perfusion provides the driving pressure for glomerular filtration and delivers the oxygen and nutrients to fuel solute reabsorption. Renal ischaemia is a major mechanism in acute kidney injury and may promote the progression of chronic kidney disease. Thus, quantifying renal tissue perfusion is critically important for both clinicians and physiologists. Current reference techniques for assessing renal tissue perfusion have significant limitations. Arterial spin labelling (ASL) is a magnetic resonance imaging (MRI) technique that uses magnetic labelling of water in arterial blood as an endogenous tracer to generate maps of absolute regional perfusion without requiring exogenous contrast. The technique holds enormous potential for clinical use but remains restricted to research settings. This statement paper from the PARENCHIMA network briefly outlines the ASL technique and reviews renal perfusion data in 53 studies published in English through January 2018. Renal perfusion by ASL has been validated against reference methods and has good reproducibility. Renal perfusion by ASL reduces with age and excretory function. Technical advancements mean that a renal ASL study can acquire a whole kidney perfusion measurement in less than 5-10 min. The short acquisition time permits combination with other MRI techniques that might inform drug mechanisms and renal physiology. The flexibility of renal ASL has yielded several variants of the technique, but there are limited data comparing these approaches. We make recommendations for acquiring and reporting renal ASL data and outline the knowledge gaps that future research should address.
Topics: Acute Kidney Injury; Humans; Kidney; Magnetic Resonance Imaging; Practice Guidelines as Topic; Renal Artery; Renal Circulation; Spin Labels
PubMed: 30137581
DOI: 10.1093/ndt/gfy180 -
Vascular Aug 2017Introduction Acute mesenteric ischaemia is associated with a significant morbidity and mortality. Endovascular techniques have emerged as a viable alternative treatment... (Meta-Analysis)
Meta-Analysis Review
Introduction Acute mesenteric ischaemia is associated with a significant morbidity and mortality. Endovascular techniques have emerged as a viable alternative treatment option to conventional surgery. Our objective was to conduct a systematic review of the literature and perform a meta-analysis of reported outcomes. Methods Our review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards and the protocol was registered in PROSPERO (CRD42016035667). We searched electronic information sources (MEDLINE, EMBASE, CINAHL, CENTRAL) and bibliographic lists of relevant articles to identify studies reporting outcomes of endovascular treatment for acute mesenteric ischaemia of embolic or thrombotic aetiology. We defined 30-day or in-hospital mortality and bowel resection as the primary outcome measures. We used the Newcastle-Ottawa scale to assess the methodological quality of observational studies. We calculated combined overall effect sizes using random effects models; results are reported as the odds ratio and 95% confidence interval. Results We identified 19 observational studies reporting on a total of 3362 patients undergoing endovascular treatment for acute mesenteric ischaemia. The pooled estimate of peri-interventional mortality was 0.245 (95% confidence interval 0.197-0.299), that of the requirement for bowel resection 0.326 (95% confidence interval 0.229-0.439), and the pooled estimate for acute kidney injury was 0.132 (95% confidence interval 0.082-0.204). Eight studies reported comparative outcomes of endovascular versus surgical treatment for acute mesenteric ischaemia (endovascular group, 3187 patients; surgical group, 4998 patients). Endovascular therapy was associated with a significantly lower risk of 30-day mortality (odds ratio 0.45, 95% confidence interval 0.30-0.67, P = 0.0001), bowel resection (odds ratio 0.45, 95% confidence interval 0.34-0.59, P < 0.00001) and acute renal failure (odds ratio 0.58, 95% confidence interval 0.49-0.68, P < 0.00001). No differences were identified in septic complications or the development of short bowel syndrome. Conclusion Endovascular treatment for acute mesenteric ischaemia is associated with a considerable mortality and requirement of bowel resection. However, endovascular therapy confers improved outcomes compared to conventional surgery, as indicated be reduced mortality, risk of bowel resection and acute renal failure. An endovascular-first approach should be considered in patients presenting with acute mesenteric ischaemia.
Topics: Chi-Square Distribution; Endovascular Procedures; Humans; Mesenteric Ischemia; Mesenteric Vascular Occlusion; Odds Ratio; Risk Assessment; Risk Factors; Splanchnic Circulation; Stents; Treatment Outcome
PubMed: 28121281
DOI: 10.1177/1708538116689353