Citations

Background/Objective: Clostridioides difficile infection (CDI) is a common healthcare-associated ailment, presenting major health and economic challenges, especially for the elderly. Despite its prevalence, comprehensive data about CDI’s impact on the elderly are limited. Methods: This study used the Global Burden of Disease Study 2019 data to analyze CDI trends from 2000 to 2019, considering factors like sex, region, and sociodemographic index (SDI). Results: This study revealed that CDI caused approximately 18,181 deaths and 252,709 disability-adjusted life years (DALYs) among the elderly worldwide. The Americas showed the highest CDI burden, while the Eastern Mediterranean saw the steepest rate increase from 2000 to 2019. Regions with a high SDI also displayed substantial CDI impact. Conclusions: The escalating burden of CDI in the elderly, especially in high-SDI areas and the Americas, emphasizes an urgent need for targeted public health strategies.

Thyroid Ultrasound (US) is the primary method to evaluate thyroid nodules. Deep learning (DL) has been playing a significant role in evaluating thyroid cancer. We propose a DL-based pipeline to detect and classify thyroid nodules into benign or malignant groups relying on two views of US imaging. Transverse and longitudinal US images of thyroid nodules from 983 patients were collected retrospectively. Eighty-one cases were held out as a testing set, and the rest of the data were used in five-fold cross-validation (CV). Two You Look Only Once (YOLO) v5 models were trained to detect nodules and classify them. For each view, five models were developed during the CV, which was ensembled by using non-max suppression (NMS) to boost their collective generalizability. An extreme gradient boosting (XGBoost) model was trained on the outputs of the ensembled models for both views to yield a final prediction of malignancy for each nodule. The test set was evaluated by an expert radiologist using the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS). The ensemble models for each view achieved a mAP0.5 of 0.797 (transverse) and 0.716 (longitudinal). The whole pipeline reached an AUROC of 0.84 (CI 95%: 0.75–0.91) with sensitivity and specificity of 84% and 63%, respectively, while the ACR-TIRADS evaluation of the same set had a sensitivity of 76% and specificity of 34% (p-value = 0.003). Our proposed work demonstrated the potential possibility of a deep learning model to achieve diagnostic performance for thyroid nodule evaluation.

Background: While criteria for the diagnosis of nosocomial pneumonias exist, objective definitions are a challenge and there is no gold standard for diagnosis. We analyzed the impact of the implementation of a logical, consensus-based diagnostic and treatment protocol for managing nosocomial pneumonias in the cardiovascular surgery intensive care unit (CVS-ICU). Methods: We conducted a quasi-experimental, interrupted time series analysis to evaluate the impact of a diagnostic and treatment protocol for nosocomial pneumonias in the CVS-ICU. Impacts were measured relative to patient outcomes, diagnostic processes, and antimicrobial stewardship improvement. Descriptive statistics were used to analyze results. Results: Overall, 35 pre-protocol and 39 post-protocol patients were included. Primary clinical variables suggesting pneumonia in pre- and post-protocol patients were new lung consolidation (50% vs. 71%), new leukocytosis (59% vs. 64%), and positive culture (32% vs. 55%). Appropriate diagnostic testing improved (23% vs. 54%, p = 0.008) after protocol implementation. The proportion of patients meeting the criteria for nosocomial pneumonia (77% vs. 87%) was not statistically significant, though more patients in the post-protocol group met probable diagnostic criteria (51% vs. 77%). Duration of therapy was not significantly different (6 days [IQR = 5.0, 10.0] vs. 7 days [IQR = 6.0, 9.0]). Conclusions: The implementation of a diagnostic and treatment protocol for management of nosocomial pneumonias in the CVS-ICU resulted in improved diagnostic accuracy, advanced antimicrobial and diagnostic stewardship efforts, and laboratory cost savings without an adverse impact on patient-centered outcomes.

Abstract Background Celiac disease (CeD) has an estimated prevalence of 1%–3%. The classical clinical presentation is malabsorption, but now patients may present with more subtle symptoms such as constipation, osteoporosis, or iron deficiency anemia. Children may also present with poor growth. CeD has a strong genetic component, and high-risk groups include first-degree relatives with CeD, patients with co-existing autoimmune diseases, and patients with chromosomal aberrations. Content Diagnostic tests for CeD include duodenal histology, serology, and genetic testing. Duodenal histology has traditionally been the gold standard of diagnosis. However, serological tests, especially IgA tissue transglutaminase antibodies (TTG-IgA), are widely used and diagnostic algorithms are based primarily on TTG-IgA as a starting point. Human leukocyte antigen typing may also be incorporated to determine genetic risk for CeD. Guidelines for children endorse biopsy avoidance provided high levels of TTG-IgA, with diagnostic accuracy being comparable to duodenal biopsy. Confirmation may be achieved by identifying IgA endomysial antibodies in a separate blood sample. Subjects with low positive TTG-IgA levels and subjects with IgA deficiency need a biopsy to establish a diagnosis of CeD. The clinical follow-up of CeD usually includes a repeat TTG-IgA examination. In adults, healing may be delayed or incomplete, and a rare consequence of refractory celiac disease is transformation to enteric T-cell lymphoma. Summary Laboratory testing, in particular TTG-IgA, plays a central role in the diagnosis and has an accuracy comparable to histology. Diagnostic algorithms utilizing laboratory testing are critical for the development of novel strategies to improve diagnosis.

Abstract Purpose: Lenvatinib, a potent multikinase inhibitor, improves progression-free survival (PFS) in patients with radioiodine (RAI)-refractory differentiated thyroid cancer; however, most patients experience disease progression, warranting further therapy. We evaluated the efficacy and safety of lenvatinib plus pembrolizumab in these patients. Patients and Methods: We enrolled patients with progressive, RAI-refractory differentiated thyroid cancer who were either naïve to multikinase inhibitors (cohort 1) or who had progressed on lenvatinib (cohort 2). Patients received oral lenvatinib daily (cohort 1, 20 mg; cohort 2, dose at progression) and intravenous pembrolizumab (200 mg) every 21 days. Results: In cohorts 1 and 2, 30 and 27 patients were enrolled, respectively. Adverse events were consistent with those observed in other cancers. In cohort 1, the confirmed overall response rate was 65.5%. There were no complete responses (primary endpoint). The 12- and 18-month PFS were 72.0% and 58.0%, respectively, and the median PFS was 26.8 months. In cohort 2, the confirmed overall response rate was 16% (primary endpoint), and the median PFS was 10.0 months (95% confidence interval, 7.0–17.9 months). Tumor histology, driver mutations, and immune-related biomarkers, including PD-L1 expression, thyroid-specific antibody levels, and CD8+ T-cell tumor infiltrate, did not correlate with response to therapy. Increased baseline peripheral blood monocytes and neutrophil to lymphocyte ratio were associated with a worse PFS in cohort 1. Conclusions: Lenvatinib plus pembrolizumab may enhance the durability of lenvatinib monotherapy in lenvatinib-naïve patients. Furthermore, the addition of pembrolizumab may be a viable salvage therapy for patients who have progressed on lenvatinib.

Purpose of review This review provides an update on current management strategies for giant cell arteritis (GCA), emphasizing the need for alternative therapies to reduce disease relapses and mitigate glucocorticoid (GC)-related morbidity. Recent findings The standard of care for GCA has traditionally involved prolonged use of GC, and recent studies are exploring faster GC tapering regimens in an effort to reduce adverse effects while maintaining disease control. Randomized clinical trials have highlighted the efficacy of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, in reducing disease flares and sparing GCs. However, the optimal treatment duration with TCZ is unknown and patients remain at risk of relapse after treatment discontinuation. An unmet therapeutic need persists for patients who are not candidates for TCZ, and for those who have inadequate response to this biologic. Therefore, investigations into alternative therapies such as targeting interleukin-17A, blocking T-cell activation or inhibiting the Janus kinase–signal transducer and activator of transcription pathway, showcase potential avenues for tailored treatments. Summary While GCs remain the cornerstone of therapy, TCZ emerges as a promising GC-sparing agent. Ongoing research targeting different pathways implicated in GCA pathogenesis have led to encouraging results. However, the preliminary nature of these findings necessitates larger randomized controlled trials to establish their efficacy conclusively.

The long-term survivorship of patients diagnosed with cancer has improved due to accelerated detection and rapidly evolving cancer treatment strategies. As such, the evaluation and management of cancer therapy related complications has become increasingly important, including cardiovascular complications. These have been captured under the umbrella term “cardiotoxicity” and include left ventricular dysfunction and heart failure, acute coronary syndromes, valvular abnormalities, pericardial disease, arrhythmia, myocarditis, and vascular complications. These complications add to the burden of cardiovascular disease (CVD) or are risk factors patients with cancer treatment are presenting with. Of note, both pre- and newly developing CVD is of prognostic significance, not only from a cardiovascular perspective but also overall, potentially impacting the level of cancer therapy that is possible. Currently, there are varying recommendations and practices regarding CVD risk assessment and mitigating strategies throughout the cancer continuum. This article provides an overview on this topic, in particular, the role of cardiac imaging in the care of the patient with cancer. Furthermore, it summarizes the current evidence on the spectrum, prevention, and management of chemotherapy-related adverse cardiac effects.

Abstract Aims Compared with those without obesity, patients with obesity-related heart failure with preserved ejection fraction (HFpEF) have worse symptoms, haemodynamics, and outcomes. Current weight loss strategies (diet, drug, and surgical) work through decreased energy intake rather than increased expenditure and cause significant loss of skeletal muscle mass in addition to adipose tissue. This may have adverse implications for patients with HFpEF, who already have reduced skeletal muscle mass and function and high rates of physical frailty. Mitochondrial uncoupling agents may have unique beneficial effects by producing weight loss via increased catabolism rather than reduced caloric intake, thereby causing loss of adipose tissue while sparing skeletal muscle. HU6 is a controlled metabolic accelerator that is metabolized to the mitochondrial uncoupling agent 2,4-dinotrophenol. HU6 selectively increases carbon oxidation from fat and glucose while also decreasing toxic reactive oxygen species (ROS) production. In addition to sparing skeletal muscle loss, HU6 may have other benefits relevant to obesity-related HFpEF, including reduced specific tissue depots contributing to HFpEF; improved glucose utilization; and reduction in systemic inflammation via both decreased ROS production from mitochondria and decreased cytokine elaboration from excess, dysfunctional adipose. Methods We describe the rationale and design of HuMAIN-HFpEF, a Phase 2a randomized, double-blind, placebo-controlled, dose-titration, parallel-group trial in patients with obesity-related HFpEF to evaluate the effects of HU6 on weight loss, body composition, exercise capacity, cardiac structure and function, metabolism, and inflammation, and identify optimal dosage for future Phase 3 trials. Conclusions HuMAIN will test a promising novel agent for obesity-related HFpEF.

Asymptomatic high-grade carotid stenosis is an important therapeutic target for stroke prevention. For decades, the ACAS (Asymptomatic Carotid Atherosclerosis Study) and ACST (Asymptomatic Carotid Surgery Trial) trials provided most of the evidence supporting endarterectomy for patients with asymptomatic high-grade stenosis who were otherwise good candidates for surgery. Since then, transfemoral/transradial carotid stenting and transcarotid artery revascularization have emerged as alternatives to endarterectomy for revascularization. Advances in treatments against atherosclerosis have driven down the rates of stroke in patients managed without revascularization. SPACE-2 (Stent-Protected Angioplasty Versus Carotid Endarterectomy-2), a trial that included endarterectomy, stenting, and medical arms, failed to detect significant differences in stroke rates among treatment groups, but the study was stopped well short of its recruitment goal. CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) will be able to clarify whether revascularization by stenting or endarterectomy remains efficacious under conditions of intensive medical management. Transcarotid artery revascularization has a favorable periprocedural risk profile, but randomized trials comparing it to intensive medical management are lacking. Features like intraplaque hemorrhage on MRI and echolucency on B-mode ultrasonography can identify patients at higher risk of stroke with asymptomatic stenosis. High-grade stenosis with poor collaterals can cause hemispheric hypoperfusion, and unstable plaque can cause microemboli, both of which may be treatable risk factors for cognitive impairment. Evidence that there are patients with carotid stenosis who benefit cognitively from revascularization is presently lacking. New risk factors are emerging, like exposure to microplastics and nanoplastics. Strategies to limit exposure will be important without specific medical therapies.

Introduction: Improved treatments for children with congenital heart disease (CHD) have led to a growing interest in long-term functional outcomes such as health-related quality of life (HRQOL). Studies on HRQOL in children with CHD have yielded contradictory results. In this study, we aimed to perform a systematic review and meta-analysis to analyze the effect of surgery on HRQOL outcomes in children with CHD in low-income and middle-income countries. Methods: A comprehensive search for articles was performed using the Medline (PubMed), Scopus, and Embase databases from their inception to September 5, 2023. Studies reporting QOL outcomes in children <18 years and published in English were included. Results: Of the 1239 records screened, 10 studies, including 1721 participants, were included in the study. The overall QOL was significantly better in the control group than in the children who underwent surgery for CHD (P=0.04, standard mean difference of −0.62, 95% CI: −1.2 to −0.04), and the overall QOL was significantly better in the children with CHD after surgery than before surgery (P=0.05, standard mean difference of −0.56, 95% CI: −1.11 to −0.01). Conclusion: The QOL of children from low-income and middle-income countries who undergo surgery for CHD is significantly poorer than that of controls in all dimensions except the emotional domain. Meanwhile, surgery has the greatest impact on improving the physical domain in children with CHD after surgery. Strategies to improve HRQOL in this subgroup of patients should be further investigated.