Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.

Is prostatic adenocarcinoma detectable by urine cytology-A multicenter retrospective review.

INTRODUCTION: Urine cytology is robust for the diagnosis of urothelial lesions, but data on the detection rates of prostatic adenocarcinoma in urine cytology is limited. In this study, a multicenter review was performed to define the clinical role of urine cytology in diagnosis of prostatic adenocarcinoma. METHODS: Cytologic diagnoses of lower tract urine cytology specimens with histology-proven prostatic adenocarcinoma from three institutions, from a period of over two decades, were reviewed. Clinicopathological parameters-tumor grade, stage, histologic features, and preanalytical factors-prostate-specific antigen (PSA) level and lesion size, were retrieved and compared with cytologic diagnoses. RESULTS: In total, 2115 urine cytology specimens from 1119 patients were retrieved. The atypia (or above/C3+) and suspicious (or above/C4+) rates were 19.48% and 3.36%. Bilobar and extracapsular involvement, lymphovascular invasion, Gleason score, and International Society of Urological Pathology grade were associated with a positive urine diagnosis (p < 0.05). The atypia (C3+) and suspicious (C4+) rates of urine cytology in patients with a PSA level of ≤4.0 ng/mL was paradoxically higher (p < 0.01), but PSA levels correlated positively with urine diagnosis at higher cutoffs (>10, >20, >50, >100 ng/mL). All these factors remained significant on multivariate analysis (p < 0.05), including a negative correlation with low-PSA (≤4.0 ng/mL, p = 0.001) and positive correlation with high-PSA (>20 ng/mL, p = 0.020). Lesion size and multifocality were not associated with urine cytology diagnosis (p > 0.05). CONCLUSION: Urine cytology showed low sensitivity in detection of prostatic adenocarcinoma. Detection rates were largely positively correlated with PSA levels but not for lesion size nor multifocality, limiting its clinical utility.

Comparison of infection risk between enzalutamide and abiraterone in patients with prostate cancer.

BACKGROUND: Enzalutamide and abiraterone may differ in their immunomodulatory effects, and the prednisone coadministered with abiraterone can be immunosuppressive. This study aimed to compare the risk of different types of infection in patients with prostate cancer receiving enzalutamide or abiraterone in combination with androgen deprivation therapy. METHODS: Patients with prostate cancer receiving enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between December 1999 to March 2021 were identified in this retrospective cohort study and followed up until September 2021, death, or crossover. Outcomes, including any sepsis, pneumonia, urinary tract infection, cellulitis or skin abscess, central nervous system infections, and tuberculosis, were analyzed as both time-to-event outcomes (multivariable Fine-Gray regression, with mortality considered a competing event) and recurrent-event outcomes (multivariable negative binomial regression). RESULTS: Altogether, 1582 patients were analyzed (923 abiraterone users; 659 enzalutamide users) with a median follow-up of 10.6 months (interquartile range: 5.3-19.9 months). Compared to abiraterone users, enzalutamide users had lower cumulative incidences of sepsis (adjusted subhazard ratio [SHR] 0.70 [0.53-0.93], p = .014), pneumonia (adjusted SHR 0.76 [0.59-0.99], p = .040), and cellulitis or skin abscess (adjusted SHR 0.55 [0.39-0.79], p = .001), but not urinary tract infection (adjusted SHR 0.91 [0.62-1.35], p = .643). Associations between exposure and central nervous system infections and tuberculosis were not assessed because of low event rates. Analyzing the outcomes as recurrent events gave similar results. Enzalutamide use may be associated with a lower risk of urinary tract infection in patients with diabetes mellitus. CONCLUSIONS: Compared to abiraterone users, enzalutamide users have significantly lower risks of sepsis, pneumonia, cellulitis, or skin abscess.

Spatial Distribution and Densities of CD103+ and FoxP3+ Tumor Infiltrating Lymphocytes by Digital Analysis for Outcome Prediction in Breast Cancer.

BACKGROUND: The evaluation of tumor-infiltrating lymphocytes (TILs) for breast cancer prognosis is now established. However, the clinical value for their spatial distributions of specific immune subsets, namely CD103+ tissue-resident memory T cells FoxP3+ regulatory T ells, have not been thoroughly examined. METHOD: Representative whole sections of breast cancers were subjected to CD103 and FoxP3 double staining. Their density, ratio, and spatial features were analyzed in tumor area and tumor-stromal interface. Their associations with clinicopathological parameters and patient's prognosis were analyzed. RESULTS: CD103 TILs were closer to tumor nests than FoxP3 TILs in the tumor-stromal interface. Their densities were associated with high-grade disease, TNBC, and stromal TILs. High stromal FoxP3 (sFoxP3) TILs and close proximity of sCD103 TILs to tumor were independently associated with better survival at multivariate analysis. Subgroup analysis showed the high FoxP3 TILs density associated better survival was seen in HER2-OE and TNBC subtypes while the proximity of CD103 TILs to tumor nests associated better survival was seen in luminal cancers. CONCLUSION: The prognostic impact of CD103 and FoxP3 TILs in breast cancer depends on their spatial localization. High sFoxP3 TIL density and the lower distance of CD103 TILs from the tumor nests had independent favorable prognostic values.

Cardiac contractility modulation in patients with heart failure - A review of the literature.

Experimental in vivo and in vitro studies showed that electric currents applied during the absolute refractory period can modulate cardiac contractility. In preclinical studies, cardiac contractility modulation (CCM) was found to improve calcium handling, reverse the foetal myocyte gene programming associated with heart failure (HF), and facilitate reverse remodeling. Randomized control trials and observational studies have provided evidence about the safety and efficacy of CCM in patients with HF. Clinically, CCM therapy is indicated to improve the 6-min hall walk, quality of life, and functional status of HF patients who remain symptomatic despite guideline-directed medical treatment without an indication for cardiac resynchronization therapy (CRT) and have a left ventricular ejection fraction (LVEF) ranging from 25 to 45%. Although there are promising results about the role of CCM in HF patients with preserved LVEF (HFpEF), further studies are needed to elucidate the role of CCM therapy in this population. Late gadolinium enhancement (LGE) assessment before CCM implantation has been proposed for guiding the lead placement. Furthermore, the optimal duration of CCM application needs further investigation. This review aims to present the existing evidence regarding the role of CCM therapy in HF patients and identify gaps and challenges that require further studies.

Evaluation of breast-specific marker expression in metastatic breast cancers: Correlation with subtype switch.

AIMS: This study evaluates the utility of breast specific markers in identifying breast cancer subtypes within metastatic settings. The subtype alteration in metastatic disease and its consequent impact on breast-specific marker expression is also examined. MATERIALS AND METHODS: GATA-binding protein 3 (GATA3), mammaglobin (MMG), transcriptional repressor GATA binding 1 (TRSP1) and SRY-box transcription factor 10 (SOX10) expression were assessed in a large cohort of metastatic breast cancer (MBC) cases and correlated with the characteristics of both MBC and primary breast cancer (PBC). RESULTS: GATA3 was the most sensitive in MBC (83.1%), followed by TRPS1 (77.0%), MMG (58.5%) and SOX10 (7.1%). This trend was consistent in hormonal receptor (HR)+ and HR- MBC. Combining GATA3/TRPS1 yielded the highest detection rates in the overall cohort (90.1%) and HR+ MBC (97.1%), while TRSP1/MMG was most effective in HR- (76.2%) and TN (71.1%) MBC. Marker expression did not correlate with metastatic site, except SOX10 in lung metastases (P = 0.031). Subtype discordance between MBC and PBC occurred in 43 cases (24.4%), with GATA3 expression in HR- MBC significantly linked to subtype discordance (P = 0.005). Conversely, SOX10 expression was significantly associated with subtype concordance in HR- and TNBC (P ≤ 0.003). Despite a higher expression of GATA3 in all HR- cases, TRSP1 outperformed GATA3 in detecting concordant HR- cases (64.0% versus 38.5%). TRPS1 and SOX10 were expressed in more than 50% of concordant TNBC cases. CONCLUSIONS: The expression of breast-specific markers is mainly determined by the PBC subtype. GATA3 retains high sensitivity in HR+ cancers, even after HR loss during metastasis. TRPS1 and SOX10 are identified as valuable markers in TNBC metastasis.

TRPS1 is a promising marker for all subtypes of breast cancer.

AIMS: Trichorhinophalangeal syndrome-1 (TRPS1) has been proposed as a novel breast marker with equally high expression in breast cancer (BC) subtypes, making it a useful diagnostic tool. Here, its expression was evaluated alongside other commonly used markers [GATA3, GCDFP15, mammaglobin (MGB) and SOX10] in a large cohort of BCs (n = 1852) and their corresponding nodal metastases. Its usefulness as a diagnostic tool and its correlation with clinicopathological features were assessed. METHODS AND RESULTS: TRPS1 was expressed at 75.8% overall in the BC cohort, with at least 58% expression among BC subtypes. It was less sensitive than GATA3 for luminal and HER2-overexpressing (HER2-OE) cancers (luminal A: 82 versus 97%; luminal B: 80 versus 95%; HER2-OE: 62 versus 76%), but it was the most sensitive for TNBC (60 versus ≤ 41%). It showed a stable expression in nodal metastases (primary tumour 76 versus nodal metastasis 78%), unlike a reduced nodal expression for GATA3 (86 versus 77%). TRPS1 outperformed GATA3 in detecting non-luminal cancers when paired with other breast markers. TRPS1 and GCDFP15 was the most sensitive combination in TNBC detection, with a 76% detection rate. For TRPS1-negative and GCDFP15-negative TNBCs, SOX10 was more sensitive than GATA3 (29 versus 24%). CONCLUSIONS: TRPS1 is a highly sensitive marker for all breast cancer subtypes, outperforming GATA3 in non-luminal cancers and displaying the highest sensitivity for TNBC detection when combined with GCDFP15. It is a valuable addition to the breast marker panel for accurate identification of BC.

Human epidermal growth factor receptor 2 (HER2) status in breast cancer: practice points and challenges.

Human epidermal growth factor receptor 2 (HER2)-enriched breast cancer benefits significantly from anti-HER2 targeted therapies. This highlights the critical need for precise HER2 immunohistochemistry (IHC) interpretation serving as a triage tool for selecting patients for anti-HER2 regimens. Recently, the emerging eligibility of patients with HER2-low breast cancers for a novel HER2-targeted antibody-drug conjugate (T-DXd) adds challenges to HER2 IHC scoring interpretation, notably in the 0-1+ range, which shows high interobserver and interlaboratory staining platform variability. In this review, we navigate evolving challenges and suggest practical recommendations for HER2 IHC interpretation.

Neutrophil-lymphocyte ratio reflects tumour-infiltrating lymphocytes and tumour-associated macrophages and independently predicts poor outcome in breast cancers with neoadjuvant chemotherapy.

AIMS: The neutrophil-lymphocyte ratio (NLR) is a systemic reflection of cancer-associated inflammation and a prognostic marker for breast cancer. For the local tumour microenvironment, tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) are also highly correlated with breast cancer survival. This study aimed to explore the relationship between the circulating and local immune microenvironment, and to further delineate the prognostic role of NLR in breast cancer patients receiving neoadjuvant chemotherapy (NAC). METHODS: A cohort of breast cancer patients receiving NAC with subsequent surgery was retrieved. Clinical data were reviewed. Histological slides and CD8 immunohistochemistry from biopsy (pre-chemotherapy) and excision (postchemotherapy) specimens were assessed for TILs and TAMs. RESULTS: A total of 146 patients were included. There was a significant positive correlation between pre- and postsurgery NLR at a cut-off of 2.6 (median pre-chemotherapy NLR) (P < 0.001). NLR pre-chemotherapy was associated positively with necrosis on biopsy (P = 0.027) and excision (P = 0.021) and TAMs on excision (P = 0.049). NLR 1 year postsurgery was associated with high tumour stage (P = 0.050) and low histological grade (P = 0.008). TIL count was lower in NLR-high cases at almost all time-points by histological assessment and CD8 immunostaining (P < 0.050). In multivariate analysis, postsurgery NLR is an independent predictor for overall survival [OS; hazard ratio (HR) = 9.524, P < 0.001], breast cancer-specific survival (BCSS) (HR = 10.059, P = 0.001) and disease-free survival (DFS; HR = 2.824, P = 0.016). CONCLUSIONS: The association between NLR with tumour necrosis, TAMs and TILs illustrates an interaction between the circulating and local immune microenvironment. Late NLR is a strong indicator of outcome and may be useful for prognostication and disease monitoring.

Left Atrial Electrophysiological Properties after Pulmonary Vein Isolation Predict the Recurrence of Atrial Fibrillation: A Cohort Study.

Background: The aim of this work was to investigate left atrial electrophysiological properties for their ability to predict the recurrence of atrial fibrillation (AF) following pulmonary vein isolation (PVI). Methods: The study comprised 53 patients with AF [62 (interquartile range (IQR): 52-68) years old; 47.2% females]. High-density, three-dimensional electro-anatomic mapping using PentaRay was conducted during sinus rhythm in the left atrium (LA) immediately after PVI. LA conduction time, conduction velocity in predefined anterior and posterior routes, low voltage area percentage and distribution were assessed. Results: The AF recurrence group had longer LA conduction time compared to the non-recurrence group [11 (IQR: 10-12) ms vs. 9 (IQR: 8-10) ms, p = 0.001). The percent low voltage area was greater in the recurrence group than the non-recurrence group [31.2 (IRQ: 7.1-49.3)% vs. 7.7 (IQR: 4.3-15.2)%, p = 0.008]. Multivariate Cox regression revealed that LA conduction time independently predicted AF recurrence following ablation over a median follow-up of 235 days [IQR: 154-382 days; hazard ratio (HR): 2.37, 95% confidence interval (CI): 1.08-5.23, p = 0.031]. The optimal cut-off for LA conduction time was 98 ms [area under curve (AUC): 0.926, sensitivity: 0.833, specificity: 0.894, p < 0.01]. Kaplan-Meier analysis revealed that patients with a conduction time > 98 ms had a higher rate of AF recurrence following ablation (p < 0.001). Conclusions: Patients with longer LA conduction time after PVI had more frequent AF recurrence.

TRPV2 calcium channel promotes breast cancer progression potential by activating autophagy.

Breast cancer, the most prevalent and aggressive tumor affecting women, requires identification of disease determinants to facilitate the development of effective therapeutic strategies. Transient receptor potential vanilloid 2 (TRPV2), an ion channel highly permeable for calcium (Ca2+), is implicated in physiological and pathological processes. Nevertheless, the role of TRPV2 in breast cancer remains poorly elucidated. In this study, we found high levels of TRPV2 expression associated with advanced malignancy, thereby suggesting its potential as a biomarker for breast cancer staging. We demonstrated that TRPV2 activation promotes breast cancer cell proliferation, migration, and invasion, while silencing of TRPV2 suppresses breast cancer progression, highlighting the oncogenic role of TRPV2. Moreover, we reveal that TRPV2 facilitates cancer progression by modulating the CaMKKß/AMPK/ULK1-autophagic axis through mediating calcium influx, providing new insights into TRPV2 as a novel therapeutic target for breast cancer treatment.

Outcomes of transcatheter closure for coronary artery fistulas with or without aneurysm: A comparative study.

BACKGROUND: Coronary Artery Fistulas (CAFs) Patients with aneurysm may face severe complications, necessitating prompt treatment. However, data on the outcomes of transcatheter closure in CAFs patients with aneurysm are notably scarce. METHODS: This retrospective study included all consecutive CAFs patients who underwent transcatheter closure at Fuwai Hospital from January 2010 to December 2023. Patients were divided into two groups based on the presence of aneurysm, and baseline characteristics, anatomical features, and transcatheter closure outcomes were further compared. RESULTS: The study ultimately included 104 patients, consisting of 56 in the aneurysm group and 48 in the non-aneurysm group. Patients in the aneurysm group were younger [39.79 (16.35) versus 50.69 (13.31) years, p < 0.001] and more frequently present with heart murmurs (21.43% vs. 6.25%, p = 0.03). Multivariate logistic regression indicated that a larger fistula diameter and the presence of CCFs are independent risk factors for the presence of aneurysm in CAF patients. The procedural success rate (75% vs. 75%, P = 1), fistula recanalization rate (11.11% vs. 16.67%, p = 0.42), and reintervention rate (3.7% vs. 6.25%, p = 0.89) were similar between the aneurysm and non-aneurysm groups. CONCLUSION: A larger fistula diameters and the presence of coronary-cameral fistulas are independent risk factors for the occurrence of aneurysms in patients with CAFs. The outcomes of transcatheter closure are comparable for CAFs patients with and without aneurysm, though post-closure thrombosis within the fistula appears to be more common in patients with aneurysm.

Lower Risks of New-Onset Hepatocellular Carcinoma in Patients With Type 2 Diabetes Mellitus Treated With SGLT2 Inhibitors Versus DPP4 Inhibitors.

BACKGROUND: Type 2 diabetes mellitus (T2DM) may be a risk factor for development of hepatocellular carcinoma (HCC). The association between risk of developing HCC and treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP4i) is currently unknown. This study aimed to compare the risk of new-onset HCC in patients treated with SGLT2i versus DPP4i. METHODS: This was a retrospective cohort study of patients with T2DM in Hong Kong receiving either SGLT2i or DPP4i between January 1, 2015, and December 31, 2020. Patients with concurrent DPP4i and SGLT2i use were excluded. Propensity score matching (1:1 ratio) was performed by using the nearest neighbor search. Multivariable Cox regression was applied to identify significant predictors. RESULTS: A total of 62,699 patients were included (SGLT2i, n=22,154; DPP4i, n=40,545). After matching (n=44,308), 166 patients (0.37%) developed HCC: 36 in the SGLT2i group and 130 in the DPP4i group over 240,269 person-years. Overall, SGLT2i use was associated with lower risks of HCC (hazard ratio [HR], 0.42; 95% CI, 0.28-0.79) compared with DPP4i after adjustments. The association between SGLT2i and HCC development remained significant in patients with cirrhosis or advanced fibrosis (HR, 0.12; 95% CI, 0.04-0.41), hepatitis B virus (HBV) infection (HR, 0.32; 95% CI, 0.17-0.59), or hepatitis C virus (HCV) infection (HR, 0.41; 95% CI, 0.22-0.80). The results were consistent in different risk models, propensity score approaches, and sensitivity analyses. CONCLUSIONS: SGLT2i use was associated with a lower risk of HCC compared with DPP4i use after adjustments, and in the context of cirrhosis, advanced fibrosis, HBV infection, and HCV infection.

Initial Experience with Embolization using a Shear-Thinning Conformable Hydrogel Embolic.

A new conformable embolic agent, brand name Obsidio (Boston Scientific Inc), is indicated for embolizing hypervascular tumors and treating peripheral vessel bleeding. It is a non-Newtonian hydrogel that becomes less viscous when shear force is applied. This retrospective study examines the safety and effectiveness of the shear-thinning embolic in a single-academic-center experience. Technical and clinical success were assessed. Adverse events were defined per the SIR Adverse Events Classification. Twenty-seven patients were treated with the shear-thinning embolic in 39 vessels over 28 procedures. Technical success was achieved in 37/39 vessels (95%), with clinical success in 26/28 procedures (93%). There was one treatment-related severe adverse event (3.6%): left gastric artery embolization resulting in ischemia and subtotal gastrectomy (Grade 3). Two patients had mild adverse events (7.1%). Initial experience shows promising effectiveness of this shear-thinning embolic, though because of differences between this embolic and conventional liquid embolics, operator training is required for safe use.

Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for new-onset gastric cancer and gastric diseases in patients with type 2 diabetes mellitus: a population-based cohort study.

OBJECTIVE: To compare the risks of gastric cancer and other gastric diseases in patients with type-2 diabetes mellitus (T2DM) exposed to sodium-glucose cotransporter 2 inhibitors (SGLT2I), dipeptidyl peptidase-4 inhibitors (DPP4I) or glucagon-like peptide-1 receptor agonists (GLP1a). DESIGN: This was a population-based cohort study of prospectively collected data on patients with T2DM prescribed SGLT2I, DPP4I or GLP1a between January 1st 2015 and December 31st 2020 from Hong Kong. The outcomes were new-onset gastric cancer, peptic ulcer (PU), acute gastritis, non-acute gastritis, and gastroesophageal reflux disease (GERD). Propensity score matching (1:1) using the nearest neighbour search was performed, and multivariable Cox regression was applied. A three-arm comparison between SGLT2I, DPP4I and GLP1a was conducted using propensity scores with inverse probability of treatment weighting. RESULTS: A total of 62,858 patients (median age: 62.2 years old [SD: 12.8]; 55.93% males; SGLT2I: n = 23,442; DPP4I: n = 39,416) were included. In the matched cohort, the incidence of gastric cancer was lower in SGLT2I (Incidence rate per 1000 person-year, IR: 0.32; 95% confidence interval, CI 0.23-0.43) than in DPP4I (IR per 1000 person-year: 1.22; CI 1.03-1.42) users. Multivariable Cox regression found that SGLT2I use was associated with lower risks of gastric cancer (HR 0.30; 95% CI 0.19-0.48), PU, acute gastritis, non-acute gastritis, and GERD (p < 0.05) compared to DPP4I use. In the three-arm analysis, GLP1a use was associated with higher risks of gastric cancer and GERD compared to SGLT2I use. CONCLUSIONS: The use of SGLT2I was associated with lower risks of new-onset gastric cancer, PU, acute gastritis, non-acute gastritis, and GERD after matching and adjustments compared to DPP4I use. SGLT2I use was associated with lower risks of GERD and gastric cancer compared to GLP1a use.

The advent of RNA-based therapeutics for metabolic syndrome and associated conditions: a comprehensive review of the literature.

Metabolic syndrome (MetS) is a prevalent and intricate health condition affecting a significant global population, characterized by a cluster of metabolic and hormonal disorders disrupting lipid and glucose metabolism pathways. Clinical manifestations encompass obesity, dyslipidemia, insulin resistance, and hypertension, contributing to heightened risks of diabetes and cardiovascular diseases. Existing medications often fall short in addressing the syndrome's multifaceted nature, leading to suboptimal treatment outcomes and potential long-term health risks. This scenario underscores the pressing need for innovative therapeutic approaches in MetS management. RNA-based treatments, employing small interfering RNAs (siRNAs), microRNAs (miRNAs), and antisense oligonucleotides (ASOs), emerge as promising strategies to target underlying biological abnormalities. However, a summary of research available on the role of RNA-based therapeutics in MetS and related co-morbidities is limited. Murine models and human studies have been separately interrogated to determine whether there have been recent advancements in RNA-based therapeutics to offer a comprehensive understanding of treatment available for MetS. In a narrative fashion, we searched for relevant articles pertaining to MetS co-morbidities such as cardiovascular disease, fatty liver disease, dementia, colorectal cancer, and endocrine abnormalities. We emphasize the urgency of exploring novel therapeutic avenues to address the intricate pathophysiology of MetS and underscore the potential of RNA-based treatments, coupled with advanced delivery systems, as a transformative approach for achieving more comprehensive and efficacious outcomes in MetS patients.

The association between urine ketone and new-onset atrial fibrillation in critically ill patients.

BACKGROUND AND AIMS: New-onset atrial fibrillation (NOAF) is a common manifestation in critically ill patients. There is a paucity of evidence indicating a relationship between urinary ketones and NOAF. METHODS: Critically ill patients with urinary ketone measurements from the Medical Information Mart for Intensive Care (MIMIC-IV) database were included. The primary outcome was NOAF Propensity score matching was performed following by multivariable logistic regression. RESULTS: A total of 24,688 patients with available data of urine ketone were included in this study. The urine ketone of 4014 patients was tested positive. The average age of the included participants was 63.8 years old, and 54.5% of them were male. Result of the fully-adjusted binary logistic regression model showed that patients with positive urinary ketone was associated with a significantly lower risk of NOAF (Odds ratio, 0.79, 95% CI 0.7-0.9), compared with those with negative urinary ketone. In the subgroup analysis according to diabetic status, compared with nondiabetics, patients with diabetes had lower risk of NOAF (p-values for interaction < 0.05). Results of other subgroup analyses according to gender, age, infection, myocardial infarction, and congestive heart failure were consistent with the primary analysis. CONCLUSIONS: Positive urinary ketone body may be associated with reduced risk of NOAF in critically ill patients during intensive care unit hospitalization. Further studies are needed to clarify the underlying mechanisms.

Long-term efficacy and safety of cryoballoon ablation of atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis evaluated long-term efficacy and safety of cryoballoon ablation (CB) of atrial fibrillation (AF). METHODS: PubMed, Cochrane Library, and Web of Science were searched until July 31, 2023, for published works investigating efficacy and safety of CB of AF in which mean/median follow-up time was not less than 36 months. Safety was assessed by adverse events. Efficacy was assessed by AF recurrence, defined as any atrial arrhythmias lasting more than 30 s. RESULTS: A total of 19 clinical studies were included. After an average of 58.1 months of follow-up, the overall AF recurrence rate was about 37%. The predictors of recurrence were duration of AF (HR 1.00; 95% CI [1.00 ∼ 1.01]), early recurrence of atrial fibrillation (HR 3.96; 95%CI [1.12 ∼ 14.02]), left atrial diameter (HR 1.04; 95%CI [1.02 ∼ 1.06]), and persistent AF (HR1.47; 95% CI [1.19 ∼ 1.82]). In terms of safety, the incidence of transient phrenic paralysis (PNP) was the highest, about 3%; followed by vascular complications (about 2%); pseudoaneurysm, permanent PNP, and all-cause death was (about 1%); and pericardial effusion and stroke / TIA was very low. CONCLUSION: CB is associated with low rates of severe complications and reasonable success rates.

Application of artificial intelligence in the diagnosis and treatment of cardiac arrhythmia.

The rapid growth in computational power, sensor technology, and wearable devices has provided a solid foundation for all aspects of cardiac arrhythmia care. Artificial intelligence (AI) has been instrumental in bringing about significant changes in the prevention, risk assessment, diagnosis, and treatment of arrhythmia. This review examines the current state of AI in the diagnosis and treatment of atrial fibrillation, supraventricular arrhythmia, ventricular arrhythmia, hereditary channelopathies, and cardiac pacing. Furthermore, ChatGPT, which has gained attention recently, is addressed in this paper along with its potential applications in the field of arrhythmia. Additionally, the accuracy of arrhythmia diagnosis can be improved by identifying electrode misplacement or erroneous swapping of electrode position using AI. Remote monitoring has expanded greatly due to the emergence of contactless monitoring technology as wearable devices continue to develop and flourish. Parallel advances in AI computing power, ChatGPT, availability of large data sets, and more have greatly expanded applications in arrhythmia diagnosis, risk assessment, and treatment. More precise algorithms based on big data, personalized risk assessment, telemedicine and mobile health, smart hardware and wearables, and the exploration of rare or complex types of arrhythmia are the future direction.

The combination of high uric acid and high C-reactive protein increased the risk of cardiovascular disease: A 15-year prospective cohort study.

BACKGROUND AND AIMS: Uric acid (UA) and C-reactive protein (CRP) may interact synergistically to accelerate the initiation and progression of cardiovascular disease (CVD). This study investigated the effects of a combination of high UA and high CRP on the risks of CVD. METHODS AND RESULTS: A total of 90,270 participants recruited from the Kailuan study were included, who were divided into four groups according to the presence/absence of hyperuricemia and inflammation. Cox regression was applied to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CVD. C-statistics, net classification index (NRI), and integrated discrimination improvement (IDI) were used to compare the incremental predictive of UA, CRP, and their combined effects on CVD. Mediation analysis was to explore the impact of CRP on the association between UA and CVD. Over a median follow-up of 14.95 years, we identified 11398 incident CVD cases. Compared to the low UA/low CRP group, the high UA/low CRP, low UA/high CRP and high UA/high CRP groups showed progressively higher risks of CVD, HR (95% CI): 1.18(1.10-1.27), 1.27(1.21-1.33) and 1.50 (1.33-1.69), respectively. The incorporation of UA and CRP into the traditional China-PAR model led to improvement in the C-statistic, NRI, and IDI, and was better than incorporation of either UA or CRP alone. Mediation analysis showed that CRP mediated the association between UA and CVD, accounting for 11.57% of the total effects. CONCLUSIONS: High UA/high CRP is associated with increased risks of CVD. Incorporation of both UA and CRP provided additional value for risk stratification.