Clinical significance of perioperative Q-wave myocardial infarction: The Emory Angioplasty versus Surgery Trial

AbstractObjective: The primary end point of the Emory Angioplasty versus Surgery Trial was a composite of three events: death, Q-wave infarction, and a new large defect on 3-year postoperative thallium scan. This study examines the clinical significance of Q-wave infarction in the surgical cohort (194 patients) of the Emory trial. Methods: Twenty patients (10.3%) with Q-wave infarctions were identified: 13 patients had inferior Q-wave infarctions and seven patients had anterior, lateral, septal, or posterior Q-wave infarctions (termed anterior Q-wave infarctions). Results: In the inferior Q-wave infarction group, postoperative cardiac catheterization (at 1 year or 3 years) in 11 patients revealed normal ejection fraction (ejection fraction >55%) in 10 (91%), no wall motion abnormalities in 10 (91%), and all grafts patent in 10 (91%). In the anterior Q-wave infarction group, postoperative catheterizatiOn in six patients revealed normal ejection fractions in five (83%), no wall motion abnormalities in three (50%), and all grafts patent in three (50%). Average peak postoperative creatine kinase MB levels were as follows: no Q-wave infarction (n = 174) 37 ± 43 IU/L, inferior Q-wave infarction 40 ± 27 IU/L, and anterior Q-wave infarction 58 ± 38 IU/L. Mortality in the 20 patients with Q-wave infarctions was 5% (1/20) at 3 years; in patients without a Q-wave infarction it was 6.3% (11/174) (p = 0.64). Of 17 patients with a Q-wave infarction who underwent postoperative catheterization, 11 (65%) had a normal ejection fraction, normal wall motion, and all grafts patent with an uneventful 3-year postoperative course. Conclusions: The core laboratory screening of postoperative electrocardiograms, particularly in the case of inferior Q-wave infarctions, appears to identify a number of patients as having a Q-wave infarction with minimal clinical significance. Q-wave infarction identified in the postoperative period seems to be a weak end point with little prognostic significance and therefore not valuable for future randomized trials. (J Thorac Cardiovasc Surg 1996;112:1447-54

Radiofrequency-based chondroplasty creates a precise area of targeted chondrocyte death with minimal necrosis outside the target zone: A systematic review

PURPOSE: To systematically examine the effects of radiofrequency (RF) ablation or coblation (controlled ablation) on chondrocyte viability following knee chondroplasty in preclinical literature to determine the effectiveness and safety of RF-based techniques. METHODS: A literature search was performed in September 2022 using PubMed and Scopus using the following search terms combined with Boolean operators: chondroplasty, radiofrequency, thermal, knee, chondral defect, articular cartilage, and cartilage. The inclusion criteria consisted of preclinical studies examining the effect of RF ablation or coblation on chondrocytes during knee chondroplasty. Exclusion criteria consisted of studies reporting chondroplasty in joints other than the knee, clinical studies, in vitro studies using animal models, case reports, non-full-text articles, letters to editors, surveys, review articles, and abstracts. The following data were extracted from the included articles: author, year of publication, chondral defect location within the knee and chondral characteristics, RF probe characteristics, cartilage macroscopic description, microscopic chondrocyte description, and extracellular matrix characteristics. RESULTS: A total of 17 articles, consisting of 811 cartilage specimens, were identified. The mean specimen age was 63.4 ± 6.0 (range, 37-89) years. Five studies used monopolar RF devices, 7 studies used bipolar RF devices, whereas 4 studies used both monopolar and bipolar RF devices. Time until cell death during ablation at any power was reported in 5 studies (n = 351 specimens), with a mean time to cell death of 54.4 seconds (mean range, 23.1-64) for bipolar RF and 56.3 seconds (mean range, 12.5-64) for monopolar RF devices. Chondrocyte cell death increased with increased wattage, while treatment time was positively correlated with deeper cell death. CONCLUSIONS: In this systematic review, histologic analysis demonstrated that RF-based chondroplasty creates a precise area of targeted chondrocyte death, with minimal evidence of necrosis outside the target zone. Caution must be exercised when performing RF-based chondroplasty due to the risk of cell death with increased application time and wattage. CLINICAL RELEVANCE: Although RF ablation has demonstrated favorable results in preliminary trials, including smoother cartilage and less damage to the surrounding healthy tissue, the risks versus benefits of the procedure are largely unknown. Caution must be exercised when performing RF-based chondroplasty in the clinical setting due to the risk of cell death with increased application time and wattage

Sleep disordered breathing and fibroblast growth factor 23 in the Hispanic Community Health Study/Study of Latinos

Preclinical data suggest that hypoxia stimulates fibroblast growth factor 23 (FGF23) transcription and cleavage in osteocytes, resulting in elevated circulating c-terminal (cFGF23) levels but normal intact FGF23 (iFGF23) levels. We conducted a case-control study within the Hispanic Community Health Study/Study of Latinos to investigate whether sleep disordered breathing, as a model of hypoxemia, is independently associated with elevated cFGF23 levels in the general population and with elevated cFGF23 and iFGF23 levels in patients with chronic kidney disease (CKD), in whom FGF23 cleavage may be impaired. Cases (n = 602) had severe sleep disordered breathing defined as an apnea/hypopnea index (AHI) of ≥30. Controls without severe sleep disordered breathing (n = 602) were matched for sex and CKD stage. The median AHI in the cases was 45.8 (IQR 35.5–62.5) compared to 2.6 (IQR 0.6–8.2) in the controls. Cases had higher cFGF23 levels than controls (66.2 RU/mL, IQR 52.8–98.4 vs. 61.2 RU/mL, IQR 49.5–80.1, p value <0.001). There were no differences in iFGF23 levels between cases and controls. In adjusted linear regression and multinomial regression analyses, body mass index attenuated the relationship between severe sleep disordered breathing and cFGF23 levels. No significant relationships were seen in analyses of severe sleep disordered breathing and iFGF23 levels or in analyses of iFGF23 and cFGF23 stratified by CKD status. Additional studies using other models of intermittent and chronic hypoxia are needed to confirm whether hypoxia stimulates FGF23 transcription in humans and to determine the impact on iFGF23 levels in CKD

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Analysis of patient-directed search content and online resource quality for ulnar collateral ligament injury and surgery

Background: Patients use the Internet to learn information about injuries, yet online content remains largely unstudied. This study analyzed patient questions posed online regarding ulnar collateral ligament (UCL) tears or UCL surgical management. Methods: Three separate search strings about UCL tear and UCL surgery were queried on the Google search engine. The 300 most commonly asked questions were compiled for each topic and associated webpage information was collected from the “People also ask” section. Questions were categorized using the Rothwell classification and webpages by Journal of the American Medical Association (JAMA) benchmark criteria. Results: The most frequent UCL tear questions were “how long does it take to heal a torn UCL?” and “what is nonsurgical treatment for the UCL?” The most frequent UCL surgery question was “can you retear your UCL after surgery?” The Rothwell classification of questions for UCL tear/UCL surgery was 55%/32% policy, 38%/57% fact, and 7%/11% value with highest subcategories being indications/management (46%/25%) and technical details (24%/25%). The most common webpages were academic (39%/29%) and medical practice (24%/26%). Mean JAMA score for all 600 webpages was low (1.2), with journals (mean = 3.4) having the highest score. Medical practice (mean = 0.5) and legal websites (mean = 0.0) had the lowest JAMA scores. Only 30% of webpages provided UCL-specific information. Conclusion: Online UCL patient questions commonly pertain to technical details and injury management. Webpages suggested by search engines contain information specific to UCL tears and surgery only one-third of the time. The quality of most webpages provided to patients is poor, with minimal source transparency

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA-KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5-2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62-0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16-1·59), representing a 50% (42-58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council