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Outcomes of chronic limb-threatening ischemia revascularization in patients with chronic kidney disease in the BEST-CLI trial.
No full textBACKGROUND: Chronic limb-threatening ischemia (CLTI) in patients with chronic kidney disease (CKD) has a high risk of poor outcomes. We aimed to compare the outcomes of lower extremity revascularization in patients with CLTI stratified by CKD severity in patients enrolled in the prospective, randomized Best Endovascular vs Best Surgical Therapy in Patients with CLTI (BEST-CLI) trial.
METHODS: The BEST-CLI trial dataset was queried to categorize patients into three groups according to CKD stage. Group A includes non-CKD and CKD stages
RESULTS: A total of 1797 patients were included. Group C patients had double the risk of amputation (hazard ratio [HR], 2.13; P \u3c .001), MALE, or all-cause mortality (HR, 2.05; P \u3c .001) and more than triple the risk of all-cause mortality (HR, 3.40; P \u3c .001) compared with group A. In dialysis-dependent patients, endovascular therapy was associated with better survival, but twice the risk of reintervention compared with surgical revascularization. According to spline model analysis, hazard of MALE or all-cause mortality increased sharply at eGFR
CONCLUSIONS: The progressive nature of renal impairment in patients with CLTI threatens their survival and limb salvage and may reduce the relative benefit of open vs endovascular revascularization seen in the overall BEST-CLI trial population. In dialysis-dependent patients, endovascular therapy was associated with lower mortality but increased reintervention rate
Risk of Severe Hypoglycemia After Initiation of Noninsulin Glucose-Lowering Therapies in Adults With Type 2 Diabetes at Moderate Cardiovascular Disease Risk.
No full textIn this emulated comparative effectiveness target trial of glucagon-like peptide 1 (GLP-1) receptor agonist, sodium-glucose cotransporter 2 (SGLT2) inhibitor, dipeptidyl peptidase 4 (DPP-4) inhibitor, and sulfonylurea therapy among adults with type 2 diabetes at moderate cardiovascular disease risk, sulfonylurea use was associated with a significantly higher risk of hypoglycemia requiring emergency department or hospital care than treatment with DPP-4 inhibitors, GLP-1 receptor agonists, or SGLT2 inhibitors. This consideration can guide the choice of glucose-lowering therapy in this highly prevalent patient population, in whom avoidance of hypoglycemia is important, yet among whom the risk of severe hypoglycemia has not been examined previously
Spine surgery and readmission: Risk factors in lumbar corpectomy patients.
No full textBACKGROUND: A corpectomy of the lumbar spine is a widely performed surgical procedure with numerous indications. Previous research predominantly focused on various surgical techniques and their outcomes, lacking a general and comprehensive analysis of factors affecting this procedure. With this study, we aimed to assess the all-cause 90-day readmission rate and identify risk factors for adverse events following a lumbar corpectomy.
METHODS: Utilizing the 2020 Nationwide Readmissions Database adults (\u3e18 years) were selected by ICD-10 procedure category codes for lumbar corpectomy. Patients with adult deformity or degenerative conditions were excluded due to coding inconsistencies. Demographic information and clinical data, including comorbidities, was extracted. Patients were categorized by their readmission status. The primary outcome was readmission, with multivariable logistic regression analysis used to identify independent risk factors.
RESULTS: A total of 3,238 patients were included, with 20.8% readmitted. The readmission group was significantly older and had higher comorbidity burdens. Malignancy had the greatest odds of readmission (OR 3.172, p=.002), with spondylodiscitis also showing significant association (OR 2.177, p=.030). Fractures were significantly more frequent in the single admission group and not associated with readmission (OR 1.235, p=.551). Medical comorbidities differed significantly between the groups with a variety of them being identified as risk factors.
CONCLUSIONS: We established an all-cause 90-day readmission rate of 20.8%, which is in range of other procedures in spine surgery but underscores the severity of lumbar corpectomy. Underlying pathologies have a greater impact on the readmission rate compared to medical comorbidities. These findings highlight the importance of preoperative patient selection, especially when performing more invasive procedures. However, the study\u27s limitations may limit the generalizability of the findings
Differential associations of somatic and cognitive-affective symptoms of depression with inflammation and insulin resistance: cross-sectional and longitudinal results from the Emotional Distress Sub-Study of the GRADE study.
No full textAIMS/HYPOTHESIS: Insulin resistance and inflammation are components of a biological framework that is hypothesised to be shared by type 2 diabetes and depression. However, depressive symptoms include a large heterogeneity of somatic and cognitive-affective symptoms, and this may obscure the associations within this biological framework. Cross-sectional and longitudinal data were used to disentangle the contributions of insulin resistance and inflammation to somatic and cognitive-affective symptoms of depression.
METHODS: This secondary analysis used data from the Emotional Distress Sub-Study of the GRADE trial. Insulin resistance and inflammation were assessed using the HOMA-IR estimation and high-sensitivity C-reactive protein (hsCRP) levels, respectively, at baseline and at the study visits at year 1 and year 3 (HOMA-IR) and every 6 months (hsCRP) for up to 3 years of follow-up. Depressive symptoms were assessed at baseline using the Patient Health Questionnaire (PHQ-8), and a total score as well as symptom cluster scores for cognitive-affective and somatic symptoms were calculated. For the cross-sectional analyses, linear regression analyses were performed, with inflammation and insulin resistance at baseline as dependent variables. For the longitudinal analyses, linear mixed-effect regression analyses were performed, with inflammation and insulin resistance at the various time points as dependent variables. In all analyses, depressive symptoms (total score and symptom cluster scores) were the independent variables, controlled for important demographic, anthropometric and metabolic confounders. For the analysis of insulin resistance (HOMA-IR), data from 1321 participants were analysed. For the analysis of inflammation (hsCRP), data from 1739 participants were analysed.
RESULTS: In cross-sectional analysis and after adjustment for potential confounders, a one-unit increase in PHQ-8 total score was significantly associated with a 0.8% increase in HOMA-IR (p=0.007), but not with hsCRP (0.6% increase, p=0.283). The somatic symptom score was associated with a 5.8% increase in HOMA-IR (p=0.004). Single-item analyses of depressive symptoms showed that fatigue (3.6% increase, p=0.002) and increased/decreased appetite (3.5% increase, p=0.009) were significantly associated with HOMA-IR cross-sectionally. The cognitive-affective symptom score was not significantly associated with HOMA-IR at baseline. In longitudinal analyses, a one-unit increase in PHQ-8 total score was significantly associated with a 0.8% increase in hsCRP over time (p=0.014), but not with HOMA-IR over time (0.1% decrease, p=0.564). Again, only the somatic symptom cluster was significantly associated with hsCRP over time (5.2% increase, p=0.017), while the cognitive-affective symptom score was not.
CONCLUSION/INTERPRETATION: The results highlight the associations of depressive symptoms with markers of inflammation and insulin resistance, both cross-sectionally and longitudinally, in individuals with type 2 diabetes. In particular, somatic symptoms of depression appear to be the driver of these associations, even after controlling for concomitant conditions, with a potential role for fatigue and issues with appetite.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01794143
Combination therapy: an upcoming paradigm to improve kidney and cardiovascular outcomes in chronic kidney disease.
No full textIn this article the authors review recent advances in the treatment of chronic kidney disease (CKD) with diabetes, and summarize evidence supporting combination therapy approaches to improve patient outcomes. Driven by the global rise in diabetes, the worldwide burden of CKD has nearly doubled since the 1990s. People with CKD have notably increased risks for premature cardiovascular disease (heart and blood vessels disease), kidney failure and death. CKD, diabetes, obesity and cardiovascular disease are closely interrelated and share common risk factors. These health conditions therefore comprise what is now known as cardiovascular-kidney-metabolic (CKM) syndrome. Recently approved medications, including sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the non-steroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone, represent agents capable of reducing metabolic, kidney and cardiovascular risk through complementary mechanisms of action. Current evidence supports use of these therapies in combination. Besides providing additive protective effects, combination therapy may also help reduce side effects. For instance, using an SGLT2 inhibitor in combination with finerenone helps decrease the risk for high potassium levels. Through the multipronged approach, combination therapy allows tailoring treatment for the individual patient characteristics and needs. Several planned and ongoing clinical trials continue to study the benefits of combination therapy in people with CKM syndrome. With building evidence supporting the use of combination therapy, it is crucial to raise awareness of the importance of this treatment approach and develop processes to incorporate new therapies into every day practice to support optimal care and improved outcomes.
Abstract: The global burden of chronic kidney disease (CKD) increased by nearly 90% in the period spanning 1990 to 2016, mostly attributed to an increase in the prevalence of CKD in diabetes. People living with CKD have an elevated lifetime risk for cardiovascular disease (CVD) when compared with the general population, with risk increasing in parallel with albuminuria and kidney function decline. Metabolic disease, CKD and CVD share common risk factors including neurohumoral activation, systemic inflammation and oxidative stress, thus prompting the introduction of a broader construct of cardiovascular-kidney-metabolic (CKM) syndrome. An important rationale for the introduction of this concept are recent and ongoing therapeutic advancements fundamentally changing CKM management. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the non-steroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone have shifted the therapeutic paradigm for patients with CKD and have emerged in rapid succession as cornerstones of guideline-directed medical therapy (GDMT). Recently completed clinical trials of aldosterone synthase inhibitors and endothelin receptor antagonists have additionally reported additive antiproteinuric effects on the background of renin-angiotensin system and SGLT2 inhibition, with acceptable safety profiles. The sum of current evidence from both preclinical and clinical studies support combination therapy in the setting of CKD to achieve additive and potentially synergistic kidney and heart protection by addressing metabolic, hemodynamic, and pro-inflammatory and pro-fibrotic mechanistic pathways. This narrative review will discuss available evidence supporting combination GDMT in CKD with diabetes and additionally discuss ongoing and future trials evaluating the efficacy and safety of combination therapies for CKD with or without diabetes
Nursing and Climate Mitigation: Decarbonization.
No full textThe consequences of climate change have led to a planetary crisis. This article reviews climate change causes and what is required to mitigate, or decrease, planet-warming greenhouse gas (GHG) pollution. The international Greenhouse Gas Protocol, which provides the framework for understanding how GHGs are identified and measured, is discussed, including actions nurses can take in all practice settings. We highlight nurse leaders working to find solutions globally and the necessary elements in nursing education that will help nursing and interdisciplinary students understand and prepare for a career in a warming world. Examples are included concerning how professional organizations can drive change at scale to tackle this critical challenge
Pan-cancer immune and stromal deconvolution predicts clinical outcomes and mutation profiles.
No full textTraditional gene expression deconvolution methods assess a limited number of cell types, therefore do not capture the full complexity of the tumor microenvironment (TME). Here, we integrate nine deconvolution tools to assess 79 TME cell types in 10,592 tumors across 33 different cancer types, creating the most comprehensive analysis of the TME. In total, we found 41 patterns of immune infiltration and stroma profiles, identifying heterogeneous yet unique TME portraits for each cancer and several new findings. Our findings indicate that leukocytes play a major role in distinguishing various tumor types, and that a shared immune-rich TME cluster predicts better survival in bladder cancer for luminal and basal squamous subtypes, as well as in melanoma for RAS-hotspot subtypes. Our detailed deconvolution and mutational correlation analyses uncover 35 therapeutic target and candidate response biomarkers hypotheses (including CASP8 and RAS pathway genes)
Responsiveness of the Japanese version of the lumbar stiffness disability index.
No full textPURPOSE: We aimed to investigate the psychometric characteristics of the Japanese version of the Lumbar Stiffness Disability Index (J-LSDI) in patients undergoing lumbar spinal surgery, with a focus on its responsiveness and minimal clinically important differences (MCID).
METHODS: This prospective, single-institution cohort study enrolled adult individuals diagnosed with degenerative spinal pathologies who underwent surgical intervention approximately 1 year prior inclusion in the study. Participants were stratified into three groups according to the number of lumbar segments included in the arthrodesis construct: Group 1 (no fusion or single-level fusion); Group 2 (fusion across two to four levels); and Group 3 (fusion involving five or more levels). Within the distribution-based framework, responsiveness was quantified using effect size (ES) and standardized response mean (SRM). Areas under the receiver operating characteristic curves (AUCs) and MCID were determined for participants who reported either minimal or moderate improvement.
RESULTS: A total of 488 participants completed the J-LSDI at baseline and 1 year. In Group 1, the LSDI scores improved from preoperatively to postoperatively, with moderate ES and SRM values (ES = 0.78; SRM = 0.59). In Group 2, the preoperative and postoperative LSDI scores did not differ, with low ES and SRM values (ES = 0.13; SRM = 0.12). In Group 3, the LSDI scores worsened from preoperatively to postoperatively, with high ES and SRM values (ES = 1.20; SRM = 0.90). The optimal cutoff points for the MCID in Groups 1, 2, and 3 were - 8.0, 0.2, and 17.1, respectively. The AUCs for the MCID in Groups 1, 2, and 3 were 0.72, 0.73, and 0.76, respectively, indicating moderate accuracy. Between-group analysis of variance revealed no significant differences in preoperative LSDI scores (p = 0.40), while significant differences were observed in postoperative scores at 1 year (p \u3c 0.01).
CONCLUSION: This study underscores the clinical relevance and measurement reliability of the J-LSDI as an effective tool for evaluating the functional impact of spinal stiffness on activities of daily living among Japanese patients, in both the preoperative and postoperative phases of spinal surgery