Clinical Indications Research Articles

Cross-Sectional Analysis of Exome Sequencing Diagnosis in Patients With Neurologic Phenotypes Facing Barriers to Clinical Testing.

Exome sequencing (ES) demonstrates a 20-50 percent diagnostic yield for patients with a suspected monogenic neurologic disease. Despite the proven efficacy in achieving a diagnosis for such patients, multiple barriers for obtaining exome sequencing remain. This study set out to assess the efficacy of ES in patients with primary neurologic phenotypes who were appropriate candidates for testing but had been unable to pursue clinical testing. A total of 297 patients were identified from the UCLA Clinical Neurogenomics Research Center Biobank, and ES was performed, including bioinformatic assessment of copy number variation and repeat expansions. Information regarding demographics, clinical indication for ES, and reason for not pursuing ES clinically were recorded. To assess diagnostic efficacy, variants were interpreted by a multidisciplinary team of clinicians, bioinformaticians, and genetic counselors in accordance with the American College of Medical Genetics and Genomics variant classification guidelines. We next examined the specific barriers to testing for these patients, including how frequently insurance-related barriers such as coverage denials and inadequate coverage of cost were obstacles to pursuing exome sequencing. The cohort primarily consisted of patients with sporadic conditions (n = 126, 42.4%) of adult-onset (n = 239, 80.5%). Cerebellar ataxia (n = 225, 75.8%) was the most common presenting neurologic phenotype. Our study found that in this population of mostly adult patients with primary neurologic phenotypes that were unable to pursue exome sequencing clinically, 47 (15.8%) had diagnostic results while an additional 24 patients (8.1%) had uncertain results. Of the 297 patients, 206 were initially recommended for clinical exome but 88 (42.7%) could not pursue ES because of insurance barriers, of whom 14 (15.9%) had diagnostic findings, representing 29.8% of all patients with diagnostic findings. In addition, the incorporation of bioinformatic repeat expansion testing was valuable, identifying a total of 8 pathogenic repeat expansions (17.0% of all diagnostic findings) including 3 of the common spinocerebellar ataxias and 2 patients with Huntington disease. These findings underscore the importance and value of clinical ES as a diagnostic tool for neurogenetic disease and highlight key barriers that prevent patients from receiving important clinical information with potential treatment and psychosocial implications for patients and family members.

Levothyroxine management in Hashimoto’s thyroiditis: A comprehensive revie

Hashimoto thyroiditis and hypothyroidism are related thyroid conditions with different aetiologies and clinical manifestations. Insufficient synthesis of thyroid hormones causes hypothyroidism, which may lead to systemic symptoms that impact energy, metabolism, and overall wellness. Thyroid tissue damage mediated by the immune system is the hallmark of the autoimmune thyroid condition known as Hashimoto thyroiditis, which is the most prevalent cause of hypothyroidism. A wide range of symptoms, such as fatigue, weight gain, cold sensitivity, constipation, dry skin, and cognitive impairment, are clinical indications of hypothyroidism and Hashimoto thyroiditis. Thyroid function tests, which measure serum levels of free thyroxine, thyroid-stimulating hormone, and thyroid autoantibodies, must be performed for the diagnosis. Imaging techniques, such ultrasonography, may aid with nodular changes detection and thyroid morphology assessment. The goals of management plans for Hashimoto thyroiditis and hypothyroidism are to stop complications, relieve symptoms, and return the body to normal. The cornerstone of treatment is levothyroxine-based thyroid hormone replacement medication, which is customized for each patient depending on their clinical presentation and thyroid function testing. Dietary restrictions, patient education, and lifestyle changes are essential components of illness management.

C-Reactive Protein-Albumin Ratio Predicts Objective Response to Enfortumab Vedotin in Metastatic Urothelial Carcinoma.

Enfortumab vedotin (EV), an antibody-drug conjugate that targets Nectin-4, is used for patients with metastatic urothelial carcinoma who have experienced progression on platinum-based chemotherapy and checkpoint inhibitors. Despite the widespread use of the drug, evidence remains scarce regarding clinical indicators that can predict the response to EV treatment. We aimed to explore the predictive value of clinical indicators derived from peripheral blood tests for treatment responses to EV. We utilized records of 109 patients with metastatic urothelial carcinoma treated by EV from our multi-institutional dataset. Receiver operating characteristic curve analyses for predicting objective responses including several indicators from blood examinations, such as C-reactive protein-albumin ratio (CAR), hemoglobin, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and lactate dehydrogenase, were performed. The optimal cutoff points were determined by the Youden index. Logistic regression analyses for achieving objective responses to EV treatment were performed among these indicators. The median age of the cohort was 74 years, and the median follow-up duration was 10 months for the entire group. Median overall survival and progression-free survival from the initiation of EV were 12 and 6 months, respectively. The objective response rate and disease control rate were 48% and 70%, respectively. The receiver operating characteristic curve analysis aimed at predicting the achievement of an objective response to EV showed that the concordant index for the CAR was 0.774, significantly surpassing other indicators such as hemoglobin level, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and serum lactate dehydrogenase. The Youden index identified an optimal cutoff value of 1 for CAR (mg/L for C-reactive protein and g/dL for serum albumin level) in predicting the objective response to EV treatment. Using the cutoff value for the CAR, the cohort was divided into 32 patients (29%) with lower CAR and 77 patients (71%) with higher CAR. The objective response rate was observed to be 84% in the lower CAR group and 32% in the higher CAR group (p < 0.0001). A logistic regression analysis revealed that an Eastern Cooperative Oncology Group Performance Status ≥1 (p = 0.04) and a CAR ≥1 (p < 0.001) were identified as independent predictors for the objective response to EV. The evaluation of the CAR from a concise blood examination at the initiation of EV could effectively predict the treatment response to EV in patients with metastatic urothelial carcinoma after the progression of platinum-based chemotherapy and checkpoint inhibitors.

Written communication of whole genome sequencing results in the NHS Genomic Medicine Service: a multi-centre service evaluation.

Whole genome sequencing (WGS) is being used in diagnostic testing for certain clinical indications within the NHS Genomic Medicine Service (GMS) in England. Letter writing is an integral part of delivering results. However, no national guidelines for writing results from WGS exist. This multi-centre service evaluation used mixed methods to understand the content and readability of letters returning diagnostic, variant of uncertain significance (VUS), and no-finding results to paediatric rare disease patients. Eight Regional Genetics Services (response rate 47%) in England provided a total of 37 letters returning diagnostic (n = 13), VUS (n = 10), and no-finding (n = 14) results. Diagnostic and VUS results were usually delivered during an appointment; no-finding results were typically delivered by letter only. Letters were diverse in which content topics they covered and level of detail. No-finding letters (14/14) explained the result but were less likely to cover other topics. Diagnostic letters discussed the result (13/13), the condition (13/13), clinical genetics follow-up (13/13), clinical management (10/13), and adapting to the result (9/13). VUS letters explained the result (10/10), diagnostic uncertainty (10/10), and clinical genetics follow-up (10/10). Uncertainty was a common component of letters (33/37), irrespective of the result. Reanalysis or review after one or more years was suggested in 6/13 diagnostic, 7/10 VUS, and 6/14 no-finding letters. The mean reading level of letters corresponded to 15-17 years. Understanding how WGS results are conveyed to families during appointments, as well as how families interpret that information, is needed to provide a more comprehensive overview of results communication and inform best practices.

Diagnostic potential of TSH to HDL cholesterol ratio in vulnerable carotid plaque identification

ObjectiveThis study aimed to investigate the predictive value of the thyroid-stimulating hormone to high-density lipoprotein cholesterol ratio (THR) in identifying specific vulnerable carotid artery plaques.MethodsIn this retrospective analysis, we included 76 patients with carotid plaques who met the criteria for admission to Zhejiang Hospital from July 2019 to June 2021. High-resolution magnetic resonance imaging (HRMRI) and the MRI-PlaqueView vascular plaque imaging diagnostic system were utilized to analyze carotid artery images for the identification of specific plaque components, including the lipid core (LC), fibrous cap (FC), and intraplaque hemorrhage (IPH), and recording of the area percentage of LC and IPH, as well as the thickness of FC. Patients were categorized into stable plaque and vulnerable plaque groups based on diagnostic criteria for vulnerable plaques derived from imaging. Plaques were categorized based on meeting one of the following consensus criteria for vulnerability: lipid core area over 40% of total plaque area, fibrous cap thickness less than 65 um, or the presence of intraplaque hemorrhage. Plaques meeting the above criteria were designated as the LC-associated vulnerable plaque group, the IPH-associated group, and the FC-associated group. Multivariate logistic regression was employed to analyze the factors influencing carotid vulnerable plaques and specific vulnerable plaque components. Receiver operating characteristic (ROC) curves were used to assess the predictive value of serological indices for vulnerable carotid plaques.ResultsWe found that THR (OR = 1.976; 95% CI = 1.094–3.570; p = 0.024) and TSH (OR = 1.939, 95% CI = 1.122–3.350, p = 0.018) contributed to the formation of vulnerable carotid plaques. THR exhibited an area under the curve (AUC) of 0.704 (95% CI = 0.588–0.803) (p = 0.003), and the AUC for TSH was 0.681 (95% CI = 0.564–0.783) (p = 0.008). THR was identified as an independent predictor of LC-associated vulnerable plaques (OR = 2.117, 95% CI = 1.064–4.212, p = 0.033), yielding an AUC of 0.815. THR also demonstrated diagnostic efficacy for LC-associated vulnerable plaques.ConclusionThis study substantiated that THR and TSH have predictive value for identifying vulnerable carotid plaques, with THR proving to be a more effective diagnostic indicator than TSH. THR also exhibited predictive value and specificity in the context of LC-associated vulnerable plaques. These findings suggest that THR may be a promising clinical indicator, outperforming TSH in detecting specific vulnerable carotid plaques.

Instructions for the use of L-PRF in different clinical indications.

Autologous platelet concentrates (APCs) have demonstrated clear benefits across various clinical applications, including alveolar ridge preservation, guided tissue regeneration, guided bone regeneration, sinus floor elevation (both lateral window approach and transcrestal technique), endodontic surgery, the treatment of medication-related osteonecrosis of the jaw bones, and periodontal plastic surgery. To ensure an optimal clinical outcome, clinicians must adhere strictly to the protocol to prepare the APCs and, especially follow evidence-based surgical guidelines, often simple but crucial, to minimize the likelihood of errors. The majority of clinical trials reported on second-generation APCs [the leukocyte- and platelet-rich fibrin (L-PRF) family, including its modifications (A-PRF, A-PRF+, CGF, T-PRF, H-PRF, etc.)]. These second-generation APCs offer additional benefits compared to the first-generation APCs, making them the preferred choice for the development of clinical recommendations. These recommendations have been formulated through a meticulous examination of the available clinical data and the clinical experience of the authors of this paper.

Initial evaluation of the relationship between maximal axial vertebra rotation and the rotation deformity in adolescent idiopathic scoliosis.

This study evaluated the relationship between maximal axial vertebra rotation (maxAVR) and other clinical and radiological indexes, compared to apical vertebra rotation (AVR) in idiopathic adolescent scoliosis (AIS). Forty consecutive patients of AIS with Cobb angle of major curve > 40° were included. They were scanned by an EOS imaging system and had trunk rotational angle (TRA) measured by scoliometer. The correlation between variables was assessed using Pearson's correlation coefficient and loaded onto a meta-analysis model. There were (34 girls and 6 boys) with an average age of 13.8 ± 1.6years. AVR was maxAVR in only 47.5% (19/40) cases of the major curves and 42.3% (11/26) cases of the minor curves. The correlation between maxAVR and TRA was significantly higher than the correlation between AVR and TRA for the MT curves (p = 0.0001) and TL/L curves (p = 0.0001). On multivariate regression analysis, the magnitude of maxAVR showed a significant correlation with TRA (p = 0.0002), Cobb angle (p = 0.001), and coronal deformity angular ratio (C-DAR) (p = 0.027). The apical vertebra was not the most rotated in most cases. The correlation between maxAVR and TRA was significantly higher than the correlation between AVR and TRA. Moreover, the maxAVR was multivariately related to TRA, Cobb angle, and C-DAR. Level II, diagnostic.

Direct MR arthrography without image guidance: a practical guide, joint-by-joint.

Direct MR arthrography (dMRA) is a fundamental technique in diagnosing pathology in major peripheral joints, allowing for precise evaluation of intra-articular structures. Although injection guidance is typically performed using imaging techniques such as ultrasound or fluoroscopy, puncture via anatomical landmarks may be useful in certain circumstances where it has been proven to be a safe and effective procedure. This paper describes the indications and injection technique of dMRA, joint by joint, focusing on the different technical details, from the most common locations, like the shoulder or hip, to those with more restricted clinical indications, such as the wrist, knee, elbow, or ankle. The most relevant anatomical landmarks are detailed for each joint, aiding in the intra-articular introduction of diluted contrast, highlighting the most accessible trajectories and structures to avoid when inserting the needle. Additionally, tips are provided to facilitate proper joint distension. With all this information, this paper aims to serve as a suitable reference guide for performing dMRA without image guidance if needed.

Metabolomic-derived endotypes of age-related macular degeneration (AMD): a step towards identification of disease subgroups.

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide, with a complex pathophysiology and phenotypic diversity. Here, we apply Similarity Network Fusion (SNF) to cluster AMD patients into putative metabolomics-derived endotypes. Using a discovery cohort of 163 AMD patients from Boston, US, and a validation cohort of 214 patients from Coimbra, Portugal, we identified four distinct metabolomics-derived endotypes with varying retinal structural and functional characteristics, confirmed across both cohorts. Patients clustered into Endotype 1 exhibited a milder form of AMD and were characterized by low levels of amino acids in specific metabolic pathways. Meanwhile, patients clustered into both Endotype 3 and 4 were associated with more severe AMD and exhibited low levels of fatty acid metabolites and elevated levels of sphingomyelins and fatty acid metabolites, respectively. These preliminary findings indicate that metabolomics-derived endotyping may offer a refined strategy for categorizing AMD patients based on their specific pathophysiological underpinnings, rather than relying solely on traditional observational clinical indicators.

Future of factor XI inhibitors in cardiovascular practice.

Anticoagulation is indicated for treatment and prevention of arterial and venous thrombosis. Targeting different steps of the coagulation process, currently available anticoagulants entail an increased risk of bleeding, which detrimentally impacts on prognosis and hinders the administration of an effective antithrombotic regimen. Factor XI (FXI) inhibition has emerged as a strategy to uncouple prevention of thrombosis from bleeding. Indeed, while FXI is crucial for the amplification phase in pathological thrombosis, it is ancillary in physiological hemostasis. A comprehensive search in several scientific databases has been performed to identify relevant studies in the field. In addition, ongoing trials have been searched for in proper datasets to provide an updated and comprehensive assessment of the current state of investigations on FXI inhibition. Many compounds have been tested to inhibit FXI at different stages (i.e., synthesis, activation, or interactions with target molecules and coagulation factors). These include antisense oligonucleotides, monoclonal antibodies, small molecules, natural peptides and aptamers. In phase 2 studies, FXI inhibitors reduced thrombotic complications without any corresponding increase in bleeding. FXI inhibitors were noninferior and potentially superior to low-molecular-weight heparin in orthopedic surgery and reduced bleeding compared to apixaban in patients with atrial fibrillation. FXI inhibition is also under testing in other conditions, including end-stage renal disease, cancer, or noncardioembolic stroke. FXI inhibition represents a promising and rapidly emerging approach for a number of clinical indications. This article reviews the rationale, evidence, pharmacology, and future applications of FXI inhibition.

Nurse-sensitive quality and benchmarking in hospitals striving for Magnet® or Pathway® designation: A qualitative study.

To examine if and how selected German hospitals use nurse-sensitive clinical indicators and perspectives on national/international benchmarking. Qualitative study. In 2020, 18 expert interviews were conducted with key informants from five purposively selected hospitals, being the first in Germany implementing Magnet® or Pathway®. Interviews were analyzed using content analysis with deductive-inductive coding. The study followed the COREQ guideline. Three major themes emerged: first, limited pre-existence of and necessity for nurse-sensitive data. Although most interviewees reported data collection for hospital-acquired pressure ulcers and falls with injuries, implementation varied and interviewees highlighted the necessity to develop additional nurse-sensitive indicators for the German context. Second, the theme creating an enabling data environment comprised building clinicians' acceptance, establishing a data culture, and reducing workload by using electronic health records. Third, challenges and opportunities in establishing benchmarking were identified but most interviewees called for a national or European benchmarking system. The need for further development of nurse-sensitive clinical indicators and its implementation in practice was highlighted. Several actions were suggested at hospital level to establish an enabling data environment in clinical care, including a nationwide or European benchmarking system. Involving nurses in data collection, comparison and benchmarking of nurse-sensitive indicators and their use in practice can improve quality of patient care. Nurse-sensitive indicators were rarely collected, and a need for action was identified. The study results show research needs on nurse-sensitive indicators for Germany and Europe. Measures were identified to create an enabling data environment in hospitals. An initiative was started in Germany to establish a nurse-sensitive benchmarking capacity. Clinical practitioners and nurse/clinical managers were interviewed.

Radiomics of Intrahepatic Cholangiocarcinoma and Peritumoral Tissue Predicts Postoperative Survival: Development of a CT-Based Clinical-Radiomic Model.

For many tumors, radiomics provided a relevant prognostic contribution. This study tested whether the computed tomography (CT)-based textural features of intrahepatic cholangiocarcinoma (ICC) and peritumoral tissue improve the prediction of survival after resection compared with the standard clinical indices. All consecutive patients affected by ICC who underwent hepatectomy at six high-volume centers (2009-2019) were considered for the study. The arterial and portal phases of CT performed fewer than 60days before surgery were analyzed. A manual segmentation of the tumor was performed (Tumor-VOI). A 5-mm volume expansion then was applied to identify the peritumoral tissue (Margin-VOI). The study enrolled 215 patients. After a median follow-up period of 28months, the overall survival (OS) rate was 57.0%, and the progression-free survival (PFS) rate was 34.9% at 3years. The clinical predictive model of OS had a C-index of 0.681. The addition of radiomic features led to a progressive improvement of performances (C-index of 0.71, including the portal Tumor-VOI, C-index of 0.752 including the portal Tumor- and Margin-VOI, C-index of 0.764, including all VOIs of the portal and arterial phases). The latter model combined clinical variables (CA19-9 and tumor pattern), tumor indices (density, homogeneity), margin data (kurtosis, compacity, shape), and GLRLM indices. The model had performance equivalent to that of the postoperative clinical model including the pathology data (C-index of 0.765). The same results were observed for PFS. The radiomics of ICC and peritumoral tissue extracted from preoperative CT improves the prediction of survival. Both the portal and arterial phases should be considered. Radiomic and clinical data are complementary and achieve a preoperative estimation of prognosis equivalent to that achieved in the postoperative setting.

Update to the essential genomic nursing competencies and outcome indicators.

Genomic healthcare applications have relevance to all healthcare professionals including nursing, and most evidence-based clinical applications impact the quality and safety of healthcare. To guide nursing genomic competency initiatives, the Essential Nursing Competencies and Curricula Guidelines for Genetics and Genomics were established through a process of consensus in 2005. A 2009 update incorporated outcome indicators consisting of specific areas of knowledge and clinical performance indicators, to help support academic integration. Almost 20 years have elapsed since these competencies were first established, yet incorporating the competencies into general and specialty scope and standards of nursing practice is inconsistent, competency integration into curricula is highly uneven, continuing education in genomics for nurses is limited, and the genomic capacity of the nursing workforce remains low. These deficits have persisted despite substantial advances in genomic technology which substantially reduced costs and increased evidence-based clinical applications, including direct to consumer genomic tests, the integration of genomics into evidence-based guidelines, and evidence that genomics impacts the quality and safety of healthcare. The aim of this project was to update and achieve consensus on genomic competencies applicable to all registered nurses. This was a mixed methods study. The update to the competencies was performed based first on a literature review to update the competencies based on the current state of the evidence. Using the updated content, a modified Delphi study was conducted with registered nurse panelists from clinical, academic, and research settings. Once consensus was achieved, the competencies were made available through the American Nurses Association for public comment. Public comments were then reviewed and integrated as needed. The literature review resulted in a transition from genetics to genomics, given the reduction in costs, which resulted in an expansion of the scope of testing in both the germline and somatic contexts. Two Delphi rounds were required to reach consensus prior to the public comment period. Public comments were solicited through the American Nurses Association, and each comment was reviewed by the authors and addressed as indicated. The Essentials of Genomic Nursing: Competencies and Outcome Indicators constitute the minimum competency in genomics required of all registered nurses regardless of the level of academic training, role, or specialty. Evidence-based genomic applications span the entire healthcare continuum and, therefore, are relevant for all registered nurses regardless of academic training, role, practice setting, or clinical expertise. These competencies serve as the guide for the minimum requirements for registered nurse practice as well as guide curricula and continuing education for all registered nurses, including but not limited to administrators, educators, nursing leaders, practicing nurses, and researchers.

Association of clinical indicators in TMJ, craniofacial, occlusal, and upper airway changes with symptoms of pediatric obstructive sleep apnea and mouth-breathing

ABSTRACT Objective To assess the association between self-reported symptoms of pediatric OSA and clinical signs in MB children. Methods Seventy-three MB children aged 7–14 years answered an interview questionnaire on OSA symptoms in childhood, focusing on chewing, nasal, and sleep disturbances. MB children were checked for changes on the craniofacial, occlusion, TMJ, upper airway, and body posture by a multi-disciplinary team, consisting of medical residents, dental, and psychology postgraduate students. Multiple logistic regression analysis verified the association between clinical signs and self-reported symptoms. Results Reported symptoms of chewing disturbance as TMD noise, muscle pain, and morning headache were significantly associated with the presence of lip incompetence and Class II malocclusion. Sleep disturbances as snoring, waking up at night, daytime sleepiness, and sleeping with the mouth open were significantly associated with the presence of hypertrophic tonsils and obstructive Mallampati score. Conclusion Symptoms of pediatric OSA were found in mouth-breathing children, which should be carefully investigated in order to prevent OSA in the future.

Clinical observation on treatment of Alzheimer's disease with Sun's scalp-abdominal acupuncture combined with donepezil hydrochloride.

To observe the effect of scalp-abdominal acupuncture combined with donepezil hydrochloride on cognition and life ability of patients with Alzheimer's disease (AD), so as to evaluate its clinical efficacy. Sixty AD patients were collected and randomly divided into control group (30 cases) and observation group (30 cases). Patients in the control group were treated with oral donepezil hydrochloride (5 mg, once daily). Patients in the observation group were treated with scalp-abdominal acupuncture at Baihui (GV20), Yintang (GV24+), Sishencong (EX-HN1), "emotional area", Shenting (GV24), "abdominal area 1""abdominal area 8", and bilateral Fengchi (GB20), Taixi (KI3), Xuanzhong (GB39), Zusanli (ST36) on the basis of control group, and electroacupuncture (10 Hz/50 Hz, 0.5 to 5.0 mA) was applied to EX-HN1, "emotional area""abdominal area 1" and "abdominal area 8", once daily, 30 min each time. Four weeks as a course of treatment, both the two groups were treated for two consecutive courses. Before and after treatment, the mini-mental state examination (MMSE), AD assessmennt scale-cognitive subscale (ADAS-Cog) and activity of daily living scale (ADL) were evaluated. The clinical efficacy index was calculated and safety was evaluated. After treatment, the MMSE and ADL scores were higher (P<0.05) and the ADAS-Cog score was lower (P<0.05) than those before treatment in both groups. Compared with the control group, the MMSE and ADL scores were increased (P<0.05) and ADAS-Cog score was decreased (P<0.05) in the observation group. The total effective rate of the observation group (26/30, 86.67%) was higher (P<0.05) than that of the control group (23/30, 76.67%). No adverse reactions occurred in both groups during the treatment. Scalp-abdominal acupuncture combined with donepezil hydrochloride can effectively improve the cognitive ability and daily living ability of AD patients, and the efficacy is better than that of oral donepezil hydrochloride alone.

A propensity score matched comparison of pulsed field versus hybrid ablation in patients with long standing persistent atrial fibrillation

Abstract Introduction On one hand pulsed-field ablation (PFA) has shown favourable data in terms of safety and efficiency for pulmonary veins isolation (PVI). One the other hand, hybrid ablation results in better outcomes in patients with persistent atrial fibrillation (AF), as it combines a thoracoscopic epicardial and transvenous endocardial approach in a single procedure. Purpose Aim of this study was to to compare 1-year follow-up data of patients with long standing persistent AF undergoing PVI and posterior wall isolation using PFA, and hybrid AF ablation. Methods Consecutive patients with long standing persistent AF undergoing a first PVI with PFA at our institution were included. For comparison, patients with long standing persistent AF undergoing a first PVI with hybrid ablation were selected using a 1:1 nearest neighbor propensity score matching. Hybrid AF ablation was performed in a one-step procedure: (i) thoracoscopic ablation followed by (ii) endocardial mapping and eventual ablation. All patients received PVI and posterior wall isolation in both group. Additional lesions were performed based on clinical indication and physician judgement. The primary endpoint was recurrence of atrial tachyarrhythmia after 12 months of follow-up (with a blanking period of 3 months). Results A total of 130 patients with persistent AF underwent hybrid ablation and 72 patients underwent PFA. 85 patients (age:67.5±9.7 years, 68.2% males, CHA2DS2-VASc: 2.5±1.3) with long standing persistent AF underwent their first AF ablation (PFA N= 39; Hybrid N = 46). After a 1-year follow-up, freedom from atrial tachyarrhythmia recurrence was 74.4% with PFA and 71.7% with hybrid ablation (p = 0.786). After propensity score matching, a total of 39 matched pairs of PFA and hybrid first AF ablation remained. The result remained unchanged and no significant difference was observed between treatment cohorts after matching (Figure 1, p=0.039). Conclusion In a propensity score matched analysis of patients with long standing persistent AF, freedom from any atrial tachyarrhythmia 1 year after AF ablation using PFA was favourable and at least as good as with hybrid ablation.

Construction and alidation of a severity prediction model for acute pancreatitis based on CT severity index: A retrospective case-control study.

To construct and internally and externally validate a nomogram model for predicting the severity of acute pancreatitis (AP) based on the CT severity index (CTSI).A retrospective analysis of clinical data from 200 AP patients diagnosed at the Hefei Third Clinical College of Anhui Medical University from June 2019 to June 2022 was conducted. Patients were classified into non-severe acute pancreatitis (NSAP, n = 135) and severe acute pancreatitis (SAP, n = 65) based on final clinical diagnosis. Differences in CTSI, general clinical features, and laboratory indicators between the two groups were compared. The LASSO regression model was used to select variables that might affect the severity of AP, and these variables were analyzed using multivariate logistic regression. A nomogram model was constructed using R software, and its AUC value was calculated. The accuracy and practicality of the model were evaluated using calibration curves, Hosmer-Lemeshow test, and decision curve analysis (DCA), with internal validation performed using the bootstrap method. Finally, 60 AP patients treated in the same hospital from July 2022 to December 2023 were selected for external validation.LASSO regression identified CTSI, BUN, D-D, NLR, and Ascites as five predictive factors. Unconditional binary logistic regression analysis showed that CTSI (OR = 2.141, 95%CI:1.369-3.504), BUN (OR = 1.378, 95%CI:1.026-1.959), NLR (OR = 1.370, 95%CI:1.016-1.906), D-D (OR = 1.500, 95%CI:1.112-2.110), and Ascites (OR = 5.517, 95%CI:1.217-2.993) were independent factors influencing SAP. The established prediction model had a C-index of 0.962, indicating high accuracy. Calibration curves demonstrated good consistency between predicted survival rates and actual survival rates. The C-indexes for internal and external validation were 0.935 and 0.901, respectively, with calibration curves close to the ideal line.The model based on CTSI and clinical indicators can effectively predict the severity of AP, providing a scientific basis for clinical decision-making by physicians.

The relationship between adipose tissue RAAS activity and the risk factors of prediabetes in different ethnicities: A protocol for a systematic review and meta-analysis.

The incidence and prevalence of prediabetes has become a global concern. The risk factors of prediabetes, such as insulin resistance, adiposity, lipotoxicity and obesity, in conjunction with the alteration of the renin-angiotensin-aldosterone system (RAAS), have been positively correlated with the high morbidity and mortality rate. Thus, this systematic review seeks to establish the relationship between the risk factors of prediabetes, namely insulin resistance adiposity, lipotoxicity, obesity and the RAAS. Therefore, a synthesis of these risk factors, their clinical indicators and the RAAS components will be compiled in order to establish the association between the RAAS alteration and obesity in prediabetic patients. This protocol for a systematic review was developed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) standards. This will be accomplished by searching clinical Medical Subject Headings categories in MEDLINE with full texts, EMBASE, Web of Science, PubMed, Cochrane Library, Academic Search Complete, ICTRP and ClinicalTrial.gov. Reviewers will examine all of the findings and select the studies that meet the qualifying criteria. To check for bias, the Downs and Black Checklist will be used, followed by a Review Manager v5. A Forrest plot will be used for the meta-analysis and sensitivity analysis. Furthermore, the strength of the evidence will be assessed utilizing the Grading of Recommendations Assessment, Development, and Evaluation procedure (GRADE). The protocol has been registered with PROSPERO CRD42022320252. This systematic review and meta-analysis will include published randomized clinical trials, observational studies and case-control studies from the years 2000 to 2022.

Cardioneuroablation for vasovagal syncope. Results from an EHRA Survey

Abstract Background Cardioneuroablation (CNA) is a recently introduced catheter-based therapy for vasovagal syncope (VVS), involving the modulation of the cardiac autonomic nervous system. Over the past decade, the body of evidence supporting CNA has consistently grown, sparking increased interest, and leading to broader adoption of this novel therapy for VVS treatment. However, several knowledge gaps persist, particularly concerning clinical indications, methodology, and long-term outcomes. Purpose The aim of this survey is to provide a comprehensive overview of the daily utilization of CNA in Europe. Methods and Results Among 204 participants, half reported that they are already performing CNA in their centres. The survey indicated CNA as an emerging therapy, with most centres initiating this treatment within the last two years. A significant majority of those who responded (71%) adopted a systematic approach by targeting ganglionated plexuses (GPs) in both the right atrium (RA) and left atrium (LA) as their first-line approach. The second most common approach (16%) involved performing ablation LA GPs only in the cases where there is no response following RA ablation. Figure 1 shows the GPs usually targeted for ablation. The most frequent procedural endpoint was the increase in the heart rate. Ninety percent of respondents relied on an anatomical approach for GP localization, while 59% also guided the procedure using electrogram analysis. Less frequently used approaches included pre-procedural imaging (20%), high-frequency stimulation (17%), and spectral analysis (10%). Only 11% of physicians discharged patients who underwent CNA without anticoagulation or antiplatelet therapy. In most cases (58%), respondents discharged their patients with anticoagulation, while 28% on single antiplatelet therapy. Overall, CNA is considered an effective procedure (80% of responders rating its effectiveness at or above 70%) and a safe procedure (with an estimated 1% rate of procedure-related complications, with symptomatic sinus tachycardia being the most frequently reported). Conclusions This survey confirmed high expectations for the future of this therapy, as most responders anticipate that CNA will be indicated as a first-line therapy for patients with recurrent cardioinhibitory VVS. Future efforts are necessary to standardize the procedural flow and peri-procedural patient management.

A Self-Polymerizing Mesh of Nano-Tethers for the Mechanical Constraint of Degraded Intervertebral Discs—A Review of 25 Years of Pre-Clinical and Early Clinical Research

Genipin polymers are self-forming tensile-load-carrying oligomers, derived from the gardenia fruit, that covalently bond to amines on collagen. The potential therapeutic mechanical benefits of a non-discrete in situ forming mesh of genipin oligomers for degraded spinal discs were first conceived in 1998. Over more than two decades, numerous studies have demonstrated the immediate mechanical effects of this injectable, intra-annular polymeric mesh including an early demonstration of an effect on clinical outcomes for chronic or recurrent discogenic low back pain. This literature review focused on articles investigating mechanical effects in cadaveric animal and human spinal discs, biochemical mechanism of action studies, articles describing the role of mechanical degradation in the pathogenesis of degenerative disc disease, initial clinical outcomes and articles describing current discogenic low back pain treatment algorithms. On the basis of these results, clinical indications that align with the capabilities of this novel injectable polymer-based treatment strategy are discussed. It is intended that this review of a novel nano-scale material-based solution for mechanical deficiencies in biologically limited tissues may provide a helpful example for other innovations in spinal diseases and similarly challenging musculoskeletal disorders.