A Cohort Study

[Posted 29/Feb/2024]

AUDIENCE: Internal Medicine

KEY FINDINGS: Patients achieving surgical remission of CD have higher incidence of autoimmune disease than age- and sex-matched patients with NFPAs. Family history of autoimmune disease is a potential risk factor. Adrenal insufficiency may be a trigger.

BACKGROUND: Glucocorticoids suppress inflammation. Autoimmune disease may occur after remission of Cushing’s disease (CD). However, the development of autoimmune disease in this context is not well described. Purpose of this study is to determine 1) the incidence of autoimmune disease in patients with CD after surgical remission compared with patients with nonfunctioning pituitary adenomas (NFPAs) and 2) the clinical presentation of and risk factors for development of autoimmune disease in CD after remission.

DETAILS: Cumulative incidence of new-onset autoimmune disease at 3 years after surgery. Assessment for hypercortisolemia included late-night salivary cortisol levels, 24-hour urine free cortisol (UFC) ratio (UFC value divided by the upper limit of the normal range for the assay), and dexamethasone suppression tests. Cumulative incidence of new-onset autoimmune disease at 3 years after surgery was higher in patients with CD (10.4% [95% CI, 5.7% to 15.1%]) than in those with NFPAs (1.6% [CI, 0% to 4.6%]) (hazard ratio, 7.80 [CI, 2.88 to 21.10]). Patients with CD showed higher prevalence of postoperative adrenal insufficiency (93.8% vs. 16.5%) and lower postoperative nadir serum cortisol levels (63.8 vs. 282.3 nmol/L) than patients with NFPAs. Compared with patients with CD without autoimmune disease, those who developed autoimmune disease had a lower preoperative 24-hour UFC ratio (2.7 vs. 6.3) and a higher prevalence of family history of autoimmune disease (41.2% vs. 20.9%).

Copyright © American College of Physicians. All Rights Reserved.

Source: Nyanyo, D. D., Mikamoto, M., Galbiati, F., et al. (2024). Autoimmune Disorders Associated With Surgical Remission of Cushing's Disease: A Cohort Study. Annals of Internal Medicine. Published: February 20, 2024. DOI: 10.7326/M23-2024.

A Systematic Review and Meta-Analysis

[Posted 14/Jul/2024]

AUDIENCE: Endocrinology, Cardiology

KEY FINDINGS: SGLT2 inhibitors reduced heart failure events and cardiovascular death in patients with heart failure, type 2 diabetes, chronic kidney disease, and atherosclerotic cardiovascular disease. These effects were consistent across a wide range of subgroups within these populations. This supports the eligibility of a large population with cardiorenal-metabolic diseases for treatment with SGLT2 inhibitors.

BACKGROUND: Sodium-glucose co-transporter-2 (SGLT2) inhibitors have been studied in patients with heart failure, type 2 diabetes, chronic kidney disease, atherosclerotic cardiovascular disease, and acute myocardial infarction. Individual trials were powered to study composite outcomes in one disease state. We aimed to evaluate the treatment effect of SGLT2 inhibitors on specific clinical endpoints across multiple demographic and disease subgroups.

DETAILS: In this systematic review and meta-analysis, authors queried online databases (PubMed, Cochrane CENTRAL, and SCOPUS) up to Feb 10, 2024, for primary and secondary analyses of large trials (n>1000) of SGLT2 inhibitors in patients with heart failure, type 2 diabetes, chronic kidney disease, and atherosclerotic cardiovascular disease (including acute myocardial infarction). Outcomes studied included composite of first hospitalisation for heart failure or cardiovascular death, first hospitalisation for heart failure, cardiovascular death, total (first and recurrent) hospitalisation for heart failure, and all-cause mortality. Effect sizes were pooled using random-effects models. Authors included 15 trials (N=100,952). Compared with placebo, SGLT2 inhibitors reduced the risk of first hospitalisation for heart failure by 29% in patients with heart failure (hazard ratio [HR] 0.71 [95% CI 0.67-0.77]), 28% in patients with type 2 diabetes (0.72 [0.67-0.77]), 32% in patients with chronic kidney disease (0.68 [0.61-0.77]), and 28% in patients with atherosclerotic cardiovascular disease (0.72 [0.66-0.79]). SGLT2 inhibitors reduced cardiovascular death by 14% in patients with heart failure (HR 0.86 [95% CI 0.79-0.93]), 15% in patients with type 2 diabetes (0.85 [0.79-0.91]), 11% in patients with chronic kidney disease (0.89 [0.82-0.96]), and 13% in patients with atherosclerotic cardiovascular disease (0.87 [0.78-0.97]). The benefit of SGLT2 inhibitors on both first hospitalisation for heart failure and cardiovascular death was consistent across the majority of the 51 subgroups studied. Notable exceptions included acute myocardial infarction (22% reduction in first hospitalisation for heart failure; no effect on cardiovascular death) and heart failure with preserved ejection fraction (26% reduction in first hospitalisation for heart failure; no effect on cardiovascular death).

Copyright © Elsevier Ltd. All rights reserved.

Source: Usman, M. S., Bhatt, D. L., Hameed, I., et al. (2024). Effect of SGLT2 Inhibitors on Heart Failure Outcomes and Cardiovascular Death Across the Cardiometabolic Disease Spectrum: A Systematic Review and Meta-Analysis. The Lancet. 2024; Published: July, 2024. DOI: 10.1016/S2213-8587(24)00102-5.

Pooled Analysis of 5 Clinical Trials

[Posted 13/Jul/2024]

AUDIENCE: Hematology, Family Medicine

KEY FINDINGS: The safety profile of acalabrutinib-based therapy in this population was consistent with the known safety profile of acalabrutinib in a broad CLL population. The analysis demonstrates long-term benefit of acalabrutinib-based regimens in patients with higher-risk CLL, regardless of line of therapy.

BACKGROUND: Before targeted therapies, patients with higher-risk chronic lymphocytic leukemia (CLL), defined as del(17p) and/or TP53 mutation (TP53m), unmutated immunoglobulin heavy chain variable region genes (uIGHV), or complex karyotype (CK), had poorer prognosis with chemoimmunotherapy.

DETAILS: Bruton tyrosine kinase inhibitors (BTKis) have demonstrated benefit in higher-risk patient populations with CLL in individual trials. To better understand the impact of the second-generation BTKi acalabrutinib, authors pooled data from 5 prospective clinical studies of acalabrutinib as monotherapy or in combination with obinutuzumab (ACE-CL-001, ACE-CL-003, ELEVATE-TN, ELEVATE-RR, and ASCEND) in patients with higher-risk CLL in treatment-naive (TN) or relapsed/refractory (R/R) cohorts. A total of 808 patients were included (TN cohort, n = 320; R/R cohort, n = 488). Median follow-up was 59.1 months (TN cohort) and 44.3 months (R/R cohort); 51.3% and 26.8% of patients in the TN and R/R cohorts, respectively, remained on treatment at last follow-up. In the del(17p)/TP53m, uIGHV, and CK subgroups in the TN cohort, median progression-free survival (PFS) and median overall survival (OS) were not reached (NR). In the del(17p)/TP53m, uIGHV, and CK subgroups in the R/R cohort, median PFS was 38.6 months, 46.9 months, and 38.6 months, respectively, and median OS was 60.6 months, NR, and NR, respectively.

Copyright © The American Society of Hematology. All rights reserved.

Source: Davids, M. S., Sharman, J. P., Ghia, P., et al. (2024). Acalabrutinib-Based Regimens in Frontline or Relapsed/Refractory Higher-Risk CLL: Pooled Analysis of 5 Clinical Trials. Blood Advances. 2024; 8(13): 3345-3359. Published: July, 2024. DOI: 10.1182/bloodadvances.2023011307.

[Posted 12/Jul/2024]

AUDIENCE: Internal Medicine

KEY FINDINGS: The challenge is defining the optimal combination of biomarkers, imaging and morbidity/mortality outcomes and ensuring that they are included in future trials while minimizing the burden on patients, trialists and trial sponsors. This paper provides an overview of some of the wide array of CV, liver and kidney measurements that were discussed at the MOSAIC meeting.

BACKGROUND: Steatotic liver disease (SLD) is a worldwide public health problem, causing considerable morbidity and mortality. Patients with SLD are at increased risk for major adverse cardiovascular (CV) events, type 2 diabetes mellitus and chronic kidney disease.

DETAILS: Conversely, patients with cardiometabolic conditions have a high prevalence of SLD. In addition to epidemiological evidence linking many of these conditions, there is evidence of shared pathophysiological processes. In December 2022, a unique multi-stakeholder, multi-specialty meeting, called MOSAIC (Metabolic multi Organ Science Accelerating Innovation in Clinical Trials) was convened to foster collaboration across metabolic, hepatology, nephrology and CV disorders. One of the goals of the meeting was to consider approaches to drug development that would speed regulatory approval of treatments for multiple disorders by combining liver and cardiorenal endpoints within a single study. Non-invasive tests, including biomarkers and imaging, are needed in hepatic and cardiorenal trials. They can be used as trial endpoints, to enrich trial populations, to diagnose and risk stratify patients and to assess treatment efficacy and safety. Although they are used in proof of concept and phase 2 trials, they are often not acceptable for regulatory approval of therapies.

Copyright © John Wiley & Sons, Inc. All rights reserved

Source: Zannad, F., Sanyal, A. J., Butler, J., et al. (2024). MASLD and MASH At the Crossroads of Hepatology Trials and Cardiorenal Metabolic Trials. Journal of Internal Medicine. 2024; 296(1): 24-38. Published: July, 2024. DOI: 10.1111/joim.13793.

[Posted 11/Jul/2024]

AUDIENCE: Gastroenterology, Oncology, Internal Medicine

KEY FINDINGS: While identifying GIST or leiomyoma, the performance of CNN model was robust, which is highlighting its promising role in supporting less-experienced endoscopists and reducing interobserver agreement.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) and leiomyomas are the most common submucosal tumors of the upper digestive tract, and the diagnosis of the tumors is essential for their treatment and prognosis. However, the ability of endoscopic ultrasonography (EUS) which could correctly identify the tumor types is limited and closely related to the knowledge, operational level, and experience of the endoscopists. Therefore, the convolutional neural network (CNN) is used to assist endoscopists in determining GISTs or leiomyomas with EUS.

DETAILS: A model based on CNN was constructed according to GoogLeNet architecture to distinguish GISTs or leiomyomas. All EUS images collected from this study were randomly sampled and divided into training set (n=411) and testing set (n=103) in a ratio of 4:1. The CNN model was trained by EUS images from the training set, and the testing set was utilized to evaluate the performance of the CNN model. In addition, there were some comparisons between endoscopists and CNN models. It was shown that the sensitivity and specificity in identifying leiomyoma were 95.92%, 94.44%, sensitivity and specificity in identifying GIST were 94.44%, 95.92%, and accuracy in total was 95.15% of the CNN model. It indicates that the diagnostic accuracy of the CNN model is equivalent to skilled endoscopists, or even higher than them.

Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Source: Liu, J., Huang, J., Song, Y., et al. (2024). Differentiating Gastrointestinal Stromal Tumors From Leiomyomas of Upper Digestive Tract Using Convolutional Neural Network Model by Endoscopic Ultrasonography. Journal of Clinical Gastroenterology. 2024; 58(6): 574-579. Published: July, 2024. DOI: 10.1097/MCG.0000000000001907.

A Quasi-Experimental Study.

[Posted 10/Jul/2024]

AUDIENCE: Nursing, Family Medicine

KEY FINDINGS: Resuscitation training through the use of a high-similarity simulator was significantly more effective than utilizing a low-similarity simulator when performing basic neonatal resuscitation

BACKGROUND: Nursing graduates must have sufficient skills to perform adequately in newborn resuscitations. New nurses should be provided with appropriate situations in order to practice the necessary skills required during a newborn resuscitation. This study aimed to improve the performance of nursing students during neonatal resuscitations through the use of a Helping Babies Breathe Program.

DETAILS: This quasi-experimental study with a control group (simulator with low similarity) and an interventional group (Helping Babies Breathe Program) was conducted on 84 eighth-semester nursing students studying at Isfahan University of Medical Sciences, Iran. A resuscitation workshop was held for a single day for 5 h with students performing standard practices for each step of the resuscitation. Knowledge and skills of students were assessed using two scenarios and a standardized checklist. The mean score of knowledge and basic neonatal resuscitation skills were significantly different between the two groups before and immediately after training, as well as Post-Internship (p < 0.05). The highest score of knowledge (17.38) belonged to the intervention group. Appropriate skills are critically important when performing bag-valve-mask ventilation. Before the intervention occurred, students in the interventional group obtained the lowest scores in resuscitation skills; however, after the intervention, all interventional group students obtained a full score and demonstrated the necessary skills required for effective newborn resuscitations.

Copyright © Neonatal Nurses Association. Published by Elsevier Ltd. All rights reserved.

Source: Nazari, A., Namnabati, M., and Ajoodanian, N. (2024). Improving the Ability of Nursing Students in Neonatal Resuscitation by Using the Helping Babies Breathe Program: A Quasi-Experimental Study. Journal of Neonatal Nursing. 2024; 29(3): 453-458. Published: June, 2024. DOI: 10.1016/j.jnn.2022.06.005.