Analysis of intracardiac electrocardiogram during ill-sustained tachycardia - door to a successful troubleshooting of 'unnecessary' defibrillator discharge.

A 50-year-old gentleman with old anterior wall myocardial infarction with implantable cardioverter defibrillator (ICD, Abbott Medical, Fortify ST VR 1235-40) presented with recurrent appropriate ICD shock. The ICD stored EGM indicated a possibility of supraventricular tachycardia (SVT) rather than ventricular tachycardia (VT) when the morphology match was found high. Bundle brunch re-entry (BBR) VT was another differential. An EP study conducted on antiarrhythmic drugs (AAD) induced reproducible but only ill-sustained tachycardia too short to perform any SVT maneuvers during tachycardia. However, critical analysis of the tachycardia electrograms suggested atypical AVNRT as the most likely mechanism. The other differentials were atrial tachycardia (AT) and BBR VT. Manoeuvres during sinus rhythm and ventricular pacing excluded other diagnosis. A single point radiofrequency ablation (RFA) near the SP region cured the arrhythmia. The reason for misclassification of SVT as VT was also sought for. It was found that the shocks were received due to fulfilment of 2/3 criteria (sudden onset and regular tachycardia). Hence, he received therapy despite an appropriate morphology match favouring SVT. This is one of the known limitations of ICDs where regular SVTs (AVNRT/AVRT or AT) may receive inappropriate ICD therapies. After slow pathway modification there was no further recurrence of either SVT or VT; hence , a substrate modification was deferred.

Self-Reported ICD-11 Personality Disorder Severity in Peruvian Adolescents: Structure, Validity, and Tentative Cutoffs.

Personality disorder (PD) is particularly common in adolescents, which underscores the significance of early screening, diagnosis, and intervention. To date, the definition of PD in the new ICD-11 has not yet been investigated in adolescents. This study therefore aimed to investigate the unidimensionality and criterion validity of self-reported ICD-11 PD features in Peruvian adolescents using the Personality Disorder Severity ICD-11 (PDS-ICD-11) scale. A total of 1,073 students (63% female; age range 12-16 years) were administered the PDS-ICD-11 scale along with criterion measures of personality pathology and symptom distress. The PDS-ICD-11 score showed adequate unidimensionality and conceptually meaningful associations with external criterion variables. The findings indicate that ICD-11 PD features, as measured with the PDS-ICD-11 scale, are structurally and conceptually sound when employed with adolescents. Norm-based cutoffs derived from the present study may be used for clinical interpretation. The PDS-ICD-11 may be employed as an efficient screening tool for personality dysfunction in adolescents.

Effect of posture on the position of the subcutaneous implantable defibrillator.

BACKGROUND: The PRAETORIAN score is developed as an alternative for defibrillation testing (DFT) post subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation, and assess three aspects of implant position on a bidirectional chest X-ray. The score is validated on a standard standing chest X-ray with arms elevated in the lateral view. OBJECTIVE: We aim to evaluate the effect of different anatomical positions on the PRAETORIAN score. METHODS: Thirty S-ICD patients underwent standard posterior-anterior (PA) and lateral chest X-rays, including additional lateral views in two positions: standing with arms down and supine with arms alongside the body. PRAETORIAN score and weighted kappa coefficient were calculated for each position. RESULTS: In 8 out of 30 patients the PRAETORIAN score was ≥90 in standard position. The agreement in PRAETORIAN score was substantial (κ=0.677) for the position with the arms down and fair (κ =0.399) for the supine position. In 10 patients (33%) with the arms down the PRAETORIAN score decreased, of whom 4 changed to a lower risk category. In 16 patients (53%) the PRAETORIAN score decreased in supine position, of whom 7 changed to a lower risk category of which one patient changed from high to low risk. CONCLUSION: A supine or arms-down position during chest X-rays can result in lower PRAETORIAN scores and underestimation of associated risk on DFT failure. This emphasizes the importance of correct anatomical positioning ('arms up') during chest X-rays when using the PRAETORIAN score.

Unsupervised Feature Selection to Identify Important ICD-10 and ATC Codes for Machine Learning on a Cohort of Patients With Coronary Heart Disease: Retrospective Study.

Background: The application of machine learning in health care often necessitates the use of hierarchical codes such as the International Classification of Diseases (ICD) and Anatomical Therapeutic Chemical (ATC) systems. These codes classify diseases and medications, respectively, thereby forming extensive data dimensions. Unsupervised feature selection tackles the "curse of dimensionality" and helps to improve the accuracy and performance of supervised learning models by reducing the number of irrelevant or redundant features and avoiding overfitting. Techniques for unsupervised feature selection, such as filter, wrapper, and embedded methods, are implemented to select the most important features with the most intrinsic information. However, they face challenges due to the sheer volume of ICD and ATC codes and the hierarchical structures of these systems. Objective: The objective of this study was to compare several unsupervised feature selection methods for ICD and ATC code databases of patients with coronary artery disease in different aspects of performance and complexity and select the best set of features representing these patients. Methods: We compared several unsupervised feature selection methods for 2 ICD and 1 ATC code databases of 51,506 patients with coronary artery disease in Alberta, Canada. Specifically, we used the Laplacian score, unsupervised feature selection for multicluster data, autoencoder-inspired unsupervised feature selection, principal feature analysis, and concrete autoencoders with and without ICD or ATC tree weight adjustment to select the 100 best features from over 9000 ICD and 2000 ATC codes. We assessed the selected features based on their ability to reconstruct the initial feature space and predict 90-day mortality following discharge. We also compared the complexity of the selected features by mean code level in the ICD or ATC tree and the interpretability of the features in the mortality prediction task using Shapley analysis. Results: In feature space reconstruction and mortality prediction, the concrete autoencoder-based methods outperformed other techniques. Particularly, a weight-adjusted concrete autoencoder variant demonstrated improved reconstruction accuracy and significant predictive performance enhancement, confirmed by DeLong and McNemar tests (P<.05). Concrete autoencoders preferred more general codes, and they consistently reconstructed all features accurately. Additionally, features selected by weight-adjusted concrete autoencoders yielded higher Shapley values in mortality prediction than most alternatives. Conclusions: This study scrutinized 5 feature selection methods in ICD and ATC code data sets in an unsupervised context. Our findings underscore the superiority of the concrete autoencoder method in selecting salient features that represent the entire data set, offering a potential asset for subsequent machine learning research. We also present a novel weight adjustment approach for the concrete autoencoders specifically tailored for ICD and ATC code data sets to enhance the generalizability and interpretability of the selected features.

Prediction of heart failure events based on physiologic sensor data in HINODE defibrillator patients.

AIMS: Hospitalizations are common in patients with heart failure and are associated with high mortality, readmission and economic burden. Detecting early signs of worsening heart failure may enable earlier intervention and reduce hospitalizations. The HeartLogic algorithm is designed to predict worsening heart failure using diagnostic data from multiple device sensors. The main objective of this analysis was to evaluate the sensitivity of the HeartLogic alert calculation in predicting worsening heart failure events (HFEs). We also evaluated the false positive alert rate (FPR) and compared the incidence of HFEs occurring in a HeartLogic alert state to those occurring out of an alert state. METHODS: The HINODE study enrolled 144 patients (81 ICD and 63 CRT-D) with device sensor data transmitted via a remote monitoring system. HeartLogic alerts were then retrospectively simulated using relevant sensor data. Clinicians and patients were blinded to calculated alerts. Reported adverse events with HF symptoms were adjudicated and classified by an independent HFE committee. Sensitivity was defined as the ratio of the number of detected usable HFEs (true positives) to the total number of usable HFEs. A false positive alert was defined as an alert with no usable HFE between the alert onset date and the alert recovery date plus 30 days. The patient follow-up period was categorized as in alert state or out of alert state. The event rate ratio was the HFE rate calculated in alert to out of alert. RESULTS: The patient cohort was 79% male and had an average age of 68 ± 12 years. This analysis yielded 244 years of follow-up data with 73 HFEs from 37 patients. A total of 311 HeartLogic alerts at the nominal threshold (16) occurred across 106 patients providing an alert rate of 1.27 alerts per patient-year. The HFE rate was 8.4 times greater while in alert compared with out of alert (1.09 vs. 0.13 events per patient-year; P < 0.001). At the nominal alert threshold, 80.8% of HFEs were detected by a HeartLogic alert [95% confidence interval (CI): 69.9%-89.1%]. The median time from first true positive alert to an adjudicated clinical HFE was 53 days. The FPR was 1.16 (95% CI: 0.98-1.38) alerts per patient-year. CONCLUSIONS: Results suggest that signs of worsening HF can be detected successfully with remote patient follow-up. The use of HeartLogic may predict periods of increased risk for HF or clinically significant events, allowing for early intervention and reduction of hospitalization in a vulnerable patient population.

Unveiling a Unique Presentation of Superior Vena Cava Syndrome Succeeding a Traumatic Motor Vehicle Crash and Implantable Cardioverter-Defibrillator Lead Placement.

Superior vena cava (SVC) syndrome, once a rarity, has seen an uptick in cases with diverse origins. While this disease process is clinically diagnosable, imaging modalities and tissue biopsies further refine interventions. The clinical presentation includes but is not limited to edema of the arms, neck, and head, facial plethora, cyanosis, and or distention of subcutaneous vessels. SVC syndrome can be attributed to extrinsic compression or thrombosis in many cases. If symptoms are not life-threatening, the overall morbidity is based on the underlying root cause. Few cases have been reported with associated death due to epistaxis. However, the obstruction itself can be initially asymptomatic and then slowly progress over months to years. This case report highlights a distinct instance of SVC syndrome with notable risk factors: implantable cardioverter defibrillator placement and prior cardiac trauma status post-intervention.

Positive predictive value and sensitivity of cancer-associated venous thromboembolism diagnoses in the Danish National Patient Register.

INTRODUCTION: Hospital discharge diagnoses from administrative registries are frequently used in studies of cancer-associated venous thromboembolism, but the validity of International Classification of Diseases (ICD) codes for identifying such events is unknown. MATERIALS AND METHODS: Using patient samples from the Danish National Patient Register, we calculated positive predictive values (PPV), i.e., the proportion of registered ICD codes, which could be confirmed after manual search of the electronic health record. Sensitivity was estimated in a sample of patients with imaging-verified venous thromboembolism but without prior knowledge about their ICD coding status. Sensitivity was calculated as the proportion of these patients, who were discharged with an ICD code for venous thromboembolism. RESULTS: The overall PPV of an ICD-10 diagnosis of cancer-associated venous thromboembolism was 75.9 % (95 % confidence interval 71.3-80.0). In subgroups, the PPV was particularly low for recurrent venous thromboembolism (44.2 %), diagnoses in a secondary position (55.7 %), outpatient diagnoses (65.3 %), and diagnoses given at surgical (66.7 %), emergency wards (48.4 %), or via hospices/palliative teams (0 %). The overall sensitivity was 68 %, meaning 32 % of patients with cancer diagnosed in hospital with venous thromboembolism were discharged without any registered ICD code for venous thromboembolism. CONCLUSIONS: The positive predictive value of an ICD diagnosis of cancer-associated venous thromboembolism in the Danish Patient Register was overall adequate for research purposes, but with notable variation across subgroups. Sensitivity was limited, as 1/3 of patients with venous thromboembolism were discharged without any relevant ICD code. Cautious interpretation of incidence of cancer-associated venous thromboembolism based on administrative register-based data is warranted.

Somatic and psychiatric comorbidity in people with diagnosed gambling disorder: A Finnish nation-wide register study.

BACKGROUND AND AIMS: This is the first nation-wide register study based on a total population sample measuring the gender-specific incidences of chronic diseases and conditions among adults diagnosed with gambling disorder (GD). DESIGN, SETTING AND PARTICIPANTS: The study used aggregated data for 2011-22 retrieved from the Register of Primary Health Care visits, Care Register for Health Care and Care Register for Social Welfare, including specialized outpatient and inpatient health care, inpatient social care and institutional care and housing services with 24-hour or part-time assistance, set in mainland Finland. Participants comprised people aged 18-90+ years with GD diagnosis [corresponding to pathological gambling, International Classification of Diseases 10th revision (ICD-10) code F63.0, n = 3605; men n = 2574, women n = 1031] and the general population (n = 4 374 192). MEASUREMENTS: Incidences of somatic diseases and psychiatric disorders were calculated for the people with diagnosed GD and for the general population, separately for women and men. FINDINGS: After standardizing for age, the incidence of each diagnostic group was systematically higher for people with GD compared with the general population, except for cancer. The highest standardized incidence ratio (SIR) values were for psychiatric disorders [SIR = 234.2; 95% confidence interval (CI) = 226.1-242.4], memory disorders (SIR = 172.1; 95% CI = 119.1-234.8), nervous system diseases (SIR = 162.8; 95% CI = 152.8-173.1), chronic respiratory diseases (SIR = 150.6; 95% CI = 137.6-164.2), diabetes (SIR = 141.4; 95% CI = 127.9-155.5) and digestive diseases (SIR = 134.5; 95% CI = 127.1-142.2). CONCLUSIONS: In Finland, the incidence of chronic diseases and conditions among people with gambling disorder is higher compared with the general population, apart from cancer.

Predictors of appropriate therapies delivered by the implantable cardioverter-defibrillator in patients with coronary artery disease during long-term period.

This prospective study aimed to investigate the ability of cardiac autonomic nervous system (CANS) activity assessment to predict appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with coronary artery disease (CAD) during long-term follow-up period. We enrolled patients with CAD and ICD implantation indications that included both secondary and primary prevention of sudden cardiac death. Before ICD implantation CANS was assessed by using heart rate variability (HRV), myocardium scintigraphy with 123I-meta-iodobenzylguanidine (123I-MIBG) and erythrocyte membranes ß-adrenoreactivity (EMA). The study's primary endpoint was the documentation of appropriate ICD therapy. Of 45 (100.0%) patients, 15 (33.3%) had appropriate ICD therapy during 36 months follow-up period. Patients with appropriate ICD therapy were likely to have a higher summed 123I-MIBG score delayed (p < 0.001) and lower 123I-MIBG washout rate (p = 0.008) indicators. These parameters were independently associated with endpoint in univariable and multivariable logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.933 (95% confidence interval 0.817-0.986; sensitivity 100.00%; specificity 93.33%). Combined CANS activity assessment is useful in prediction of appropriate ICD therapy in patients with CAD during long-term follow-up period after device implantation.

Electrical storm after acute myocardial infarction treated with Radiofrequency ablation under the Escort of ICD.

The occurrence of ventricular tachycardia (VT) in patients with acute myocardial infarction (AMI) is associated with poor prognosis. Drug therapy and implantable cardioverter-defibrillators (ICDs) are effective methods to prevent sudden death. Radiofrequency (RF) catheter ablation can map the matrix and mechanism of VT, thereby effectively reducing the occurrence of ICD discharge. This paper reports on the case of a middle-aged man who underwent emergency percutaneous coronary intervention for AMI and developed VT and ventricular fibrillation on day 7 after reperfusion. An ICD was implanted. On day 19, he received catheter ablation because of refractory monomorphic ventricular tachycardia and frequent discharge of the ICD. After three months, the patient had not experienced any further ventricular tachycardia attacks. The conclusion is that RF catheter ablation can resolve the ES after myocardial infarction and significantly reduce the occurrence of ICD discharges.

Golf Swing-Induced Pacemaker Atrial Noise and Extraction: A Case Report and Literature Review.

Implantable medical devices, such as pacemakers, have significantly improved the quality of life for patients with cardiac conditions, allowing them to maintain active lifestyles. Nonetheless, these devices can present unique challenges when interacting with the wearer's physical activities, potentially leading to unforeseen complications. Here, we present a case of an 81-year-old male golfer, with a history of atrial fibrillation, congestive heart failure, and sick sinus syndrome, who experienced atrial lead noise from his pacemaker, exclusively triggered by his golf swing. This incident, which led to multiple interventions including lead extraction, reimplantation, and eventually a switch to a unipolar lead configuration, represents the first documented case of its kind. It underscores the intricate relationship between the biomechanical forces of certain sports and the functionality of implanted cardiac devices. Through detailed electrophysiology testing, this case demonstrates how specific movements inherent to the patient's golf swing could induce micro-damage to the pacemaker leads, causing noise and malfunction. The findings from this case emphasize the need for healthcare providers to perform sport-specific biomechanical evaluations and create tailored rehabilitation strategies that consider the unique physical demands placed on patients with implanted devices. This approach is important not only for diagnosing and managing similar cases but also for advancing our understanding of how to best support the active lifestyles of patients with implanted cardiac devices, ensuring their safety and longevity.

From mono to multi-causality: Towards a comprehensive perspective on understanding death.

Cause-of-death statistics are an age-old source of information for health policy and medical research. In these statistics, the presentation of data is based on the idea of an underlying cause of death, i.e. one ("the") cause of death per deceased. This idea reflects an 18th Century causal thinking and is less and less applicable to contemporary patterns of dying in high income countries with an aging population suffering from chronic diseases and multi- or comorbidity at the end of life. Therefore, today's clinical reality calls for an innovation of cause-of-death statistics. For this, I will consider contemporary philosophical ideas on causality and their application to death. I will argue multi-causality is a more comprehensive way to understand death than mono-causality, implying a change of perspective with regard to current cause-of-death statistics.

Copper-Based Composites Nanoparticles Improve Triple-Negative Breast Cancer Treatment with Induction of Apoptosis-Cuproptosis and Immune Activation.

The synergistic effect of apoptosis and cuproptosis, along with the activation of the immune system, presents a promising approach to enhance the efficacy against triple-negative breast cancer (TNBC). Here, two prodrugs are synthesized: a reactive oxygen species (ROS)-responsive prodrug PEG-TK-DOX and a glutathione (GSH)-responsive prodrug PEG-DTPA-SS-CPT. These prodrugs are self-assembled and chelated Cu2+ to prepare nanoparticle PCD@Cu that simultaneously loaded doxorubicin (DOX), camptothecin (CPT), and Cu2+. The elevated levels of ROS and GSH in TNBC cells disrupted the PCD@Cu structure, leading to the release of Cu+, DOX, and CPT and the depletion of GSH. DOX and CPT triggered apoptosis with immunogenic cell death (ICD) in TNBC cells. Simultaneously, PCD@Cu downregulated the expression of copper transporting ATPase 2 (ATP7B), causing a significant accumulation of copper ions in TNBC cells. This further induced the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT) and downregulation of iron-sulfur (Fe-S) cluster proteins, ultimately leading to cuproptosis and ICD in TNBC. In vitro and in vivo experiments confirmed that PCD@Cu induced apoptosis and cuproptosis in TNBC and activated the immune system, demonstrating strong anti-tumor capabilities. Moreover, PCD@Cu exhibited an excellent biosafety profile. Overall, this study provides a promising strategy for effective TNBC therapy.

The effects of empagliflozin on ventricular arrhythmias in heart failure patients with an implantable cardioverter-defibrillator: a double-blind randomized controlled trial.

Sodium-glucose transporter 2 (SGLT2) inhibitors such as empagliflozin are one of the main treatments for type 2 diabetes mellitus (DM2) and heart failure (HF). They have also demonstrated anti-arrhythmic effects in some preclinical and clinical studies. The purpose of this study was to assess the effects of empagliflozin on ventricular arrhythmias in HF patients with an implantable cardioverter-defibrillator (ICD). In a prospective double-blinded, randomized controlled trial of Iran County, Mashhad (72 patients 1:1), we compared the frequency and proportion of ventricular arrhythmias and ICD therapies during the 24 weeks to the prior 24 weeks. Results revealed that empagliflozin significantly reduced the frequency and proportion of ventricular tachycardia (VT)/fibrillation (VF) episodes (P = 0.019 and 0.039, respectively). Moreover, it tended to reduce the frequency and proportion of ICD therapies, including anti-tachycardia pacing (ATP) and shock. Subgroup analysis of patients with or without any antiarrhythmic drugs (digoxin, mexiletine, amiodarone, or sotalol) revealed that only patients who were previously on the antiarrhythmic drugs benefit from empagliflozin antiarrhythmic effects. In conclusion, empagliflozin exhibits anti-arrhythmic effects in HF patients with an ICD. Larger and long-term clinical studies are still needed to investigate and confirm all positive effects of SGLT2 inhibitors in this regard. Trial registration number: IRCT20120520009801N7 (Approval date: June 11, 2022).

Incidence and economics of transvenous ICD lead complications: Implications for tricuspid valve function and interventions.

BACKGROUND: Implantable cardioverter-defibrillators are used globally and are reliable, but complications related to transvenous leads remain a concern. Evidence related to the incidence and costs of those complications is heterogeneous with respect to scope and healthcare system. This analysis aims to create estimates of the incidence and costs of tricuspid valve (TV) complications, lead failures, and lead extractions from a single large real-world data set. METHODS AND RESULTS: This retrospective longitudinal cohort study used the deidentified Medicare Fee for Service administrative claims database. A total of 116 036 patients with de novo transvenous ICD implant were analyzed. Mean hospital costs were $26 903 for tricuspid valve complications, $20 851 for lead failures, and $22 278 for lead extractions. CONCLUSIONS: Transvenous ICD lead complications incur significant costs to patients, hospitals, and payers when they occur. Advancements in lead technology that reduce these complications could bring significant clinical and economic value.

A novel tool for arrhythmic risk stratification in desmoplakin gene variant carriers.

BACKGROUND AND AIMS: Pathogenic desmoplakin (DSP) gene variants are associated with the development of a distinct form of arrhythmogenic cardiomyopathy known as DSP cardiomyopathy. Patients harbouring these variants are at high risk for sustained ventricular arrhythmia (VA), but existing tools for individualized arrhythmic risk assessment have proven unreliable in this population. METHODS: Patients from the multi-national DSP-ERADOS (Desmoplakin SPecific Effort for a RAre Disease Outcome Study) Network patient registry who had pathogenic or likely pathogenic DSP variants and no sustained VA prior to enrolment were followed longitudinally for the development of first sustained VA event. Clinically guided, step-wise Cox regression analysis was used to develop a novel clinical tool predicting the development of incident VA. Model performance was assessed by c-statistic in both the model development cohort (n = 385) and in an external validation cohort (n = 86). RESULTS: In total, 471 DSP patients [mean age 37.8 years, 65.6% women, 38.6% probands, 26% with left ventricular ejection fraction (LVEF) < 50%] were followed for a median of 4.0 (interquartile range: 1.6-7.3) years; 71 experienced first sustained VA events {2.6% [95% confidence interval (CI): 2.0, 3.5] events/year}. Within the development cohort, five readily available clinical parameters were identified as independent predictors of VA and included in a novel DSP risk score: female sex [hazard ratio (HR) 1.9 (95% CI: 1.1-3.4)], history of non-sustained ventricular tachycardia [HR 1.7 (95% CI: 1.1-2.8)], natural logarithm of 24-h premature ventricular contraction burden [HR 1.3 (95% CI: 1.1-1.4)], LVEF < 50% [HR 1.5 (95% CI: .95-2.5)], and presence of moderate to severe right ventricular systolic dysfunction [HR 6.0 (95% CI: 2.9-12.5)]. The model demonstrated good risk discrimination within both the development [c-statistic .782 (95% CI: .77-.80)] and external validation [c-statistic .791 (95% CI: .75-.83)] cohorts. The negative predictive value for DSP patients in the external validation cohort deemed to be at low risk for VA (<5% at 5 years; n = 26) was 100%. CONCLUSIONS: The DSP risk score is a novel model that leverages readily available clinical parameters to provide individualized VA risk assessment for DSP patients. This tool may help guide decision-making for primary prevention implantable cardioverter-defibrillator placement in this high-risk population and supports a gene-first risk stratification approach.

Subcutaneous versus transvenous implantable cardioverter defibrillator in hypertrophic cardiomyopathy: a systematic review and meta-analysis.

Background: A subcutaneous implantable cardioverter-defibrillator (S-ICD) is an alternative to a transvenous implantable cardio defibrillator (TV-ICD). An S-ICD reduces the risk of transvenous lead placement. However, further research is required to determine how S-ICDs affect patients with hypertrophic cardiomyopathy (HCM). In this study, we investigated the comparative efficacy and safety of S-ICDs versus TV-ICDs in HCM. Methods: On December 6th, 2023, we performed a comprehensive search of the PubMed, Embase, Scopus, and Cochrane databases to identify randomized clinical trials (RCTs) and observational studies comparing S-ICDs with TV-ICDs in HCM patients published from 2004 until 2023. No language restrictions were applied. The primary outcome was appropriate shocks (AS), with inappropriate shocks (IAS), and device-related complications considered as secondary outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using a random effects model. The ROBINS-I tool was used to assess the risk of bias of the studies. Results: The search yielded 1,114 records. Seven studies comprising 4,347 HCM patients were included, of whom 3,325 (76.0%) had TV-ICDs, and 1,022 (22.6%) had S-ICDs. There were 2,564 males (58.9%). The age range was from 39.1 to 49.4 years. Compared with the TV-ICD group, the S-ICD cohort had a significantly lower incidence of device-related complications (OR 0.52; 95% CI: 0.30-0.89; P=0.02; I2=4%). Contrastingly, there were no statistically significant differences in the occurrences of AS (OR 0.49; 95% CI: 0.22-1.08; P=0.08; I2=75%) and IAS (OR 1.03; 95% CI: 0.57-1.84; P=0.93; I2=65%) between the two device modalities. In the analysis of the overall risk of bias in the studies, we found 42% of them with several, 28% with moderate, and 14% with low risk of bias. Conclusions: In HCM patients, S-ICDs were associated with a lower incidence of device-associated problems than TV-ICDs. AS and IAS incidence rates were similar between groups. These findings may assist clinicians in determining the most suitable device for treating patients with HCM.

Advancements in nanomedicine delivery systems: unraveling immune regulation strategies for tumor immunotherapy.

This review highlights the significant role of nanodrug delivery systems (NDDS) in enhancing the efficacy of tumor immunotherapy. Focusing on the integration of NDDS with immune regulation strategies, it explores their transformative impacts on the tumor microenvironment and immune response dynamics. Key advancements include the optimization of drug delivery through NDDS, targeting mechanisms like immune checkpoint blockade and modulating the immunosuppressive tumor environment. Despite the progress, challenges such as limited clinical efficacy and complex manufacturing processes persist. The review emphasizes the need for further research to optimize these systems, potentially revolutionizing cancer treatment by improving delivery efficiency, reducing toxicity and overcoming immune resistance.

[Box: see text].

Synergistic action of gemcitabine and celecoxib in promoting the antitumor efficacy of anti-programmed death-1 monoclonal antibody by triggering immunogenic cell death.

Background: Emerging evidence suggests that immunogenic chemotherapy not only kills tumor cells but also improves the immune-suppressive tumor microenvironment by inducing immunogenic cell death (ICD), leading to sustained anti-tumor effects. The lack of ICD inducers explored in lung cancer necessitates investigation into new inducers for this context, therefore, this study aims to explore whether the gemcitabine (GEM) and celecoxib can activate the immunogenic chemotherapy progress in lung cancer tissue. Methods: We assessed five chemotherapeutic agents for their ability to trigger ICD using ex vivo and in vivo experiments, including western blotting (WB), flow cytometry, and tumor preventive vaccine assays. Additionally, we evaluated the synergistic effects of GEM, celecoxib, and anti-programmed death 1 monoclonal antibody (aPD-1) in tumor-bearing mice to understand how GEM activates antitumor immunity and enhances immunochemotherapy. Results: GEM was identified as an effective ICD inducer, showing high expression of calreticulin (CRT) and heat shock protein 90 (HSP90). Co-culture with GEM-treated cells [Lewis lung carcinoma (LLC) and CMT-64] enhanced dendritic cell (DC) activity, evidenced by maturation markers and increased phagocytic capacity. Moreover, celecoxib was found to enhance ICD by reducing indoleamine 2,3-dioxygenase 1 (IDO1) expression and increasing reactive oxygen species (ROS)-based endoplasmic reticulum (ER) stress. The combination therapy [GEM, celecoxib, and aPD-1 (GCP)] exhibited potent and sustained antitumor activity in immunocompetent mice, with enhanced recruitment of tumor-infiltrating lymphocytes. Conclusions: These findings support the potential use of GCP therapy as a treatment option for lung cancer patients.