Predictors of Mortality in Acute Myocardial Infarction Complicated by Cardiogenic Shock despite Intra-Aortic Balloon Pump: Opportunities for Advanced Mechanical Circulatory Support in Asia.

Introduction: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) mortality remains high despite revascularization and the use of the intra-aortic balloon pump (IABP). Advanced mechanical circulatory support (MCS) devices, such as catheter-based ventricular assist devices (cVAD), may impact mortality. We aim to identify predictors of mortality in AMI-CS implanted with IABP and the proportion eligible for advanced MCS in an Asian population. Methods: We retrospectively analyzed a cohort of Society for Cardiovascular Angiography and Intervention (SCAI) stage C and above AMI-CS patients with IABP implanted from 2017-2019. We excluded patients who had IABP implanted for indications other than AMI-CS. Primary outcome was 30-day mortality. Binary logistic regression was used to calculate adjusted odds ratios (aOR) for patient characteristics. Results: Over the 3-year period, 242 patients (mean age 64.1 ± 12.4 years, 88% males) with AMI-CS had IABP implanted. 30-day mortality was 55%. On univariate analysis, cardiac arrest (p < 0.001), inotrope/vasopressor use prior to IABP (p = 0.004) was more common in non-survivors. Non-survivors were less likely to be smokers (p = 0.001), had lower ejection fraction, higher creatinine/ lactate and lower pH (all p < 0.001). On multi-variate analysis, predictors of mortality were cardiac arrest prior to IABP (aOR 4.00, CI 2.28-7.03), inotrope/vasopressor prior to IABP (aOR 2.41, CI 1.18-4.96), lower arterial pH (aOR 0.02, CI 0.00-0.31), higher lactate (aOR 2.42, CI 1.00-1.19), and lower hemoglobin (aOR 0.83, CI 0.71-0.98). Using institutional MCS criteria, 106 patients (44%) would have qualified for advanced MCS. Conclusions: Early mortality in AMI-CS remains high despite IABP. Many patients would have qualified for higher degrees of MCS.

The clinical value of iodine-125 seed implantation in the treatment of iodine-refractory differentiated thyroid carcinoma.

Objective: To explore the clinical benefits of 125I seed implantation for iodine-refractory differentiated thyroid cancer (RAIR-DTC). Methods: A retrospective analysis was conducted on 36 patients with RAIR-DTC who underwent radioactive 125I seed implantation from January 2015 to February 2022, involving 73 lesions. Prescription dose: 80~120 Gy. All cases were followed up at 1, 3, and 5 months postoperatively to monitor changes in tumor size, serum thyroglobulin (Tg), and serum anti-thyroglobulin antibody levels in thyrotropin-inhibited states, pain scores, and postoperative adverse reactions. The data were processed and analyzed using IBM SPSS 26.0. LER (Local Effective Rate) and LCR (Local Control Rate) were expressed as n (%), tumor diameter, Tg, and pain scores were represented as Median (Q1, Q3). Pairwise comparisons were conducted using the Wilcoxon signed-rank test, and a p-value of less than 0.05 indicated statistical significance. Results: Tumor size was significantly reduced after treatment (all P < 0.001): tumor length diameters were 32.67 (17.70, 45.72) mm, 27.45 (12.30, 39.98) mm, 20.70 (11.98, 37.58) mm, and 20.39 (10.56, 33.20) mm in the preoperative, 1-, 3-, and 5-months postoperative periods, respectively. Additionally, two consecutive post-treatment results were more minor and statistically significant than the previous results (P < 0.001). The LER at 1-, 3-, and 5-months post-surgery was 23.73%, 38.98%, and 52.54%, respectively, while the LCR at the same time points was 98.31%, 96.61%, and 94.92%, respectively. Patients' serum Tg levels decreased significantly after surgery. (P < 0.001). Serum Tg levels were measured before surgery and 1-, 3-, and 5-months post-surgery. The results showed that serum Tg levels were 249.45 (79.39, 4718.75) ng/ml, 193.40 (44.53, 2829.00) ng/ml, 192.10 (25.58, 1758.00) ng/ml, and 136.25 (16.57, 1553.25) ng/ml, respectively. Two consecutive post-treatment results were more minor and statistically significant than the previous results (P < 0.001). The patients' pain symptoms were significantly relieved after 125I brachytherapy (P < 0.001). The pain scores before 125I seed implantation and at 1, 3, and 5 months after the operation were 5.00 (4.00, 6.00), 3.00 (2.25, 4.00), 2.00 (2.00, 3.00), and 2.00 (1.00, 3.00), respectively. Conclusion: Most lesions treated with 125I seed implantation in RAIR-DTC patients showed shrinkage and improved pain symptoms. Clinical trial registration: https://www.clinicaltrials.gov, identifier NCT06362772.

CMTM 6 promotes the development of thyroid cancer by inhibiting NIS activity through activating the MAPK signaling pathway.

Thyroid cancer is the most common type of endocrine cancer. Chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing 6 (CMTM6) is recognized as one of its potential immunotherapy targets. The purpose of this study was to investigate the role and molecular mechanism of CMTM6 in regulating the development of thyroid cancer cells. In this study, expression levels of CMTM6 and the sodium/iodide symporter (NIS) were detected by qRT-PCR. Additionally, colony formation assay and flow cytometry were used to detect cell proliferation and apoptosis, while expression levels of various proteins were assessed using Western blotting. Further, the apoptosis and invasion capacity of cells were investigated by scratch and transwell experiments. Finally, the effect of CMTM6 on the epithelial-mesenchymal transition (EMT) of thyroid cancer cells was determined by immunofluorescence assay, which measured the expression levels of epithelial and mesenchymal phenotypic markers. The results of qRT-PCR experiments showed that CMTM6 was highly expressed in thyroid cancer tissues and cells. In addition, knockdown of CMTM6 expression significantly increased NIS expression. Function experiments demonstrated that small interfering (si)-CMTM6 treatment inhibited the proliferation, migration, invasion, and EMT of thyroid cancer cells, while promoting apoptosis of FTC133 cells. Furthermore, mechanistic studies showed that mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) phosphorylation were inhibited by si-CMTM6, as demonstrated by Western blot experiments. In conclusion, our findings demonstrated the role of CMTM6 in the metastasis of thyroid cancer. Briefly, CMTM6 exerts its tumor-promoting effect through the MAPK signaling pathway and could potentially be used as a valuable biomarker for thyroid cancer diagnosis and prognosis.

Non-Vitamin K Antagonist Oral Anticoagulants versus Low Molecular Weight Heparin for Cancer-Related Venous Thromboembolic Events: Individual Patient Data Meta-Analysis.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in cancer patients. Low molecular weight heparin (LMWH) has been the standard of care but new guidelines have approved the use of non-vitamin K antagonist oral anticoagulants (NOAC). By conducting an individual patient data (IPD) meta-analysis of randomised controlled trials (RCTs) comparing the outcomes of NOAC versus LMWH in cancer patients, we aim to determine an ideal strategy for the prophylaxis of VTE and prevention of VTE recurrence. Three databases were searched from inception until 19 October 2022. IPD was reconstructed from Kaplan-Meier curves. Shared frailty, stratified Cox and Royston-Parmar models were fit to compare the outcomes of venous thromboembolism recurrence and major bleeding. For studies without Kaplan-Meier curves, aggregate data meta-analysis was conducted using random-effects models. Eleven RCTs involving 4844 patients were included. Aggregate data meta-analysis showed that administering NOACs led to a significantly lower risk of recurrent VTE (RR = 0.65; 95%CI: 0.50-0.84) and deep vein thrombosis (DVT) (RR = 0.60; 95%CI: 0.40-0.90). In the IPD meta-analysis, NOAC when compared with LMWH has an HR of 0.65 (95%CI: 0.49-0.86) for VTE recurrence. Stratified Cox and Royston-Parmar models demonstrated similar results. In reducing risks of recurrent VTE and DVT among cancer patients, NOACs are superior to LMWHs without increased major bleeding.

Global Registry of Acute Coronary Events Score Underestimates Post-Acute Coronary Syndrome Mortality among Cancer Patients.

Background Patients with prior cancer are at increased risk of acute coronary syndrome (ACS) with poorer post-ACS outcomes. We aimed to ascertain if the Global Registry of Acute Coronary Events (GRACE) score accurately predicts mortality risk among patients with ACS and prior cancer. Methods We linked nationwide ACS and cancer registries from 2007 to 2018 in Singapore. A total of 24,529 eligible patients had in-hospital and 1-year all-cause mortality risk calculated using the GRACE score (2471 prior cancer; 22,058 no cancer). Results Patients with prior cancer had two-fold higher all-cause mortality compared to patients without cancer (in-hospital: 22.8% versus 10.3%, p < 0.001; 1-year: 49.0% vs. 18.7%, p < 0.001). Cardiovascular mortality did not differ between groups (in-hospital: 5.2% vs. 4.8%, p = 0.346; 1-year: 6.9% vs. 6.1%, p = 0.12). The area under the receiver operating characteristic curve of the GRACE score for prediction of all-cause mortality was less for prior cancer (in-hospital: 0.64 vs. 0.80, p < 0.001; 1-year: 0.66 vs. 0.83, p < 0.001). Among patients with prior cancer and a high-risk GRACE score > 140, in-hospital revascularization was not associated with lower cardiovascular mortality than without in-hospital revascularization (6.7% vs. 7.6%, p = 0.50). Conclusions The GRACE score performs poorly in risk stratification of patients with prior cancer and ACS.

Analysis of the Influencing Factors of Tumor Volume, Body Immunity, and Poor Prognosis after 125I Particle Therapy for Differentiated Thyroid Cancer.

Objective: To analyze the influencing factors of tumor volume, body immunity, and poor prognosis after 125I particle therapy for differentiated thyroid cancer. Methods: A total of 104 patients with differentiated TC who were treated with 125I particles during January 2020 to January 2021 was picked. These subjects were graded as low-dose group (80Gy-110Gy) and high-dose group (110Gy-140Gy) according to the minimum dose received by 90% of the target volume (D90) after surgery. The tumor volume before and after treatment was compared, and fasting venous blood was collected before and after treatment. The content of thyroglobulin (Tg) was detected by electrochemiluminescence immunoassay. The levels of absolute lymphocyte count (ALC), lymphocytes, neutrophils, and monocytes were detected on automatic blood cell analyzer. The lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ration (PLR) were calculated. The changes in the condition of patients were closely observed, and the occurrence of adverse reactions in the two groups were compared. The risk factors influencing the efficacy of 125I particle therapy for differentiated TC were analyzed through multivariate logistic regression analysis. Results: The total effective rate of patients in the low- and high-dose groups was 78.85% and 82.69%, respectively (P > 0.05). Compared with the pretreatment period, the tumor volume and Tg level in both groups were much lower (P < 0.05), and the differences in tumor volume and Tg level had no statistically significant difference between the two groups before and after treatment (P > 0.05). At 1 week of the treatment, the total incidence of adverse reactions such as nausea, radiation gastritis, radiation parotitis, and neck discomfort was obviously higher in the high-dose group than in the low-dose group (P < 0.05). At 1 month of treatment, the incidence of adverse reactions such as nausea was markedly higher in the high-dose group than in the low-dose group (P < 0.05). After treatment, serum NLR and PLR contents were memorably elevated and LMR level was sharply decreased in both groups, and serum NLR and PLR contents were higher and LMR content was lower in the high-dose group than in the low-dose group (P < 0.05). Multivariate logistic regression analysis showed that the pathological type of follicular adenocarcinoma, tumor size ≥ 2 cm, clinical stage of III~IV, distant metastasis, and high TSH level before 125I particle treatment were all risk factors related to the efficacy of 125I particle treatment of TC (P < 0.05). Conclusion: The efficacy of low-dose and high-dose 125I particles in the treatment of differentiated thyroid cancer is comparable, among which low-dose 125I particles have fewer adverse effects and have less impact on the immunity of the body, which is well tolerated by patients and can be widely used in clinical practice. In addition, the pathological type of follicular adenocarcinoma, tumor size ≥ 2 cm, clinical stage III~IV, distant metastasis, and high TSH level before 125I particle treatment are all risk factors that affect the poor effect of 125I particles on thyroid cancer treatment, and early monitoring of the above index changes can help evaluate the prognosis.

Natural Progression of Left Ventricular Function following Anthracyclines without Cardioprotective Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: Anthracyclines form the backbone of many systemic chemotherapy regimens but are accompanied by dose-limiting cardiotoxicity. We elucidate the progression and severity of cardiac function over time, in the absence of cardioprotection, which less is known about. METHODS: This PRISMA-guideline-adherent review was registered on PROSPERO (CRD42022373496). RESULTS: 26 studies met the eligibility criteria including a total of 910 patients. The overall reduction in post-anthracycline pooled mean left ventricular ejection fraction (LVEF) in placebo arms of the included randomised-controlled trials was 4.5% (95% CI, 2.6 to 6.4). The trend in LVEF showed a progressive decline until approximately 180 days, after which there was no significant change. Those receiving a cumulative anthracycline dose of 300 mg/m2 experienced a more profound reduction. The overall pooled risk of a 10% absolute decline in LVEF from baseline, or a decline to an LVEF below 50%, was 17% (95% CI: 11 to 24; I2 = 71%). Sensitivity analyses of baseline LVEF and trastuzumab treatment status did not yield significant differences. CONCLUSION: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines is required.

Branched-chain amino acid transaminase 1 inhibition attenuates childhood asthma in mice by effecting airway remodeling and autophagy.

Childhood asthma is a common chronic childhood disease. Branched-chain amino acid transaminase 1 (BCAT1) was reported to be upregulated in chronic airway diseases, while its role in childhood asthma is unclear. Asthma mouse models were established in neonatal mice by 10 µg ovalbumin (OVA) intraperitoneal injection and 3% OVA inhalational challenge. In OVA-challenged mice, BCAT1 levels were upregulated. BCAT1 inhibitor alleviated airway structure and inflammation by suppressing IgE, OVA-specific IgE and inflammatory cytokine release and inflammatory cell infiltration. BCAT1 inhibitor alleviated airway remodeling by inhibiting goblet cell hyperplasia, mucus secretion and the expression of α-SMA and collagen I/III. The BCAT1 inhibitor prevented OVA-enhanced autophagy by decreasing Beclin-1, Atg5 and LC3I/II and increasing p65 levels. In IL-13-stimulated BEAS-2B cells, rapamycin promoted inflammatory cytokine release and autophagy after BCAT1 inhibitor administration. Our research revealed that BCAT1 was upregulated in neonatal asthmatic mice and that a BCAT1 inhibitor might restrain airway inflammation and remodeling by decreasing autophagy, which offered a novel mechanistic understanding of childhood asthma.

First Medical Contact-to-Device Time and Heart Failure Outcomes Among Patients Undergoing Primary Percutaneous Coronary Intervention.

Background Expediting reperfusion during primary percutaneous coronary intervention is aimed at salvaging myocardium in ST-segment-elevation myocardial infarction. Few studies have examined the relation between reperfusion time and heart failure (HF) events. Methods and Results: We studied 7597 patients undergoing primary percutaneous coronary intervention from 2007 to 2013 in the Singapore Myocardial Infarct Registry, which captures HF at admission, postadmission in-hospital HF, and HF rehospitalization. We studied the relation of first medical contact to deployment of first device to achieve reperfusion (FTD) time with in-hospital HF events and HF rehospitalization, with mortality modeled as a competing risk. At the population level, median FTD time decreased from 91 minutes (interquartile range, 69-114) in 2007 to 58 minutes (45-75) in 2013 ( P=0.001), whereas mortality remained unchanged (in-hospital: range 5.3%-7.3%; P=0.190 and 1-year: range 7.8%-10.9%; P=0.505). HF at admission increased from 12.2% in 2007 to 18.4% in 2013, P=0.020, whereas postadmission in-hospital HF decreased from 12.8% in 2007 to 7.1% in 2013, P=0.030. HF rehospitalization increased from 1.2% in 2007 to 2.6% in 2013 ( P=0.003), for 30-day HF rehospitalization, and 3.8% in 2007 to 5.6% in 2013 ( P=0.037), for 1-year HF rehospitalization. At the individual level, among patients with HF at admission (N=1191), longer FTD time was associated with more 30-day HF rehospitalization (compared with ≤60 minutes, adjusted hazard ratio, 1.68 [0.73-3.86] for 60-90 minutes, 2.88 [1.19-6.92], for 90-120 minutes, and 2.84 [1.08-7.44] for >120 minutes). Longer FTD time was associated with a greater risk of postadmission in-hospital HF (compared with ≤60 minutes, adjusted hazard ratio, 1.18 [0.96-1.44] for 60-90 minutes, 1.59 [1.25-2.03] for 90-120 minutes, and 1.67 [1.26-2.21] for >120 minutes). Conclusions: Temporal reductions in FTD time were associated with decrease in postadmission in-hospital HF. Among patients presenting with HF at admission, delays in FTD beyond 90 minutes were associated with more 30-day HF rehospitalization.

Sleep Apnea Evolution and Left Ventricular Recovery After Percutaneous Coronary Intervention for Myocardial Infarction.

STUDY OBJECTIVES: Sleep apnea is often newly diagnosed in patients presenting with ST-segment elevation myocardial infarction (STEMI). We assessed longitudinal changes in apnea-hypopnea index (AHI) and sleep apnea phenotype after STEMI and determined its association with changes in the left ventricular ejection fraction (LVEF). METHODS: A total of 101 eligible patients with STEMI underwent consecutive sleep studies and echocardiographic studies within 5 days of admission and at 6-month follow-up. Sleep apnea (AHI ≥ 15 events/h) was further divided into obstructive sleep apnea (OSA) or central sleep apnea (CSA). RESULTS: Both AHI (mean difference -6.4 events/h, 95% confidence interval [CI] -9.6 to 3.3, P < .001) and LVEF (mean difference 2.6%, 95% CI 1.3 to 4.0, P < .001) improved from baseline to 6 months. The improvement in AHI was associated with an increase in LVEF (ß = -.47, 95% CI -.86 to -.07, P = .023) and a decrease in left ventricular end-systolic volume (LVESV) (ß = .25, 95% CI .07 to .43, P = .007). Of the patients with OSA at baseline (46%), resolution of OSA was seen in 48% at 6 months. Of those with CSA at baseline (12%), conversion to OSA was seen in 83%. In contrast, among those with no sleep apnea (42%) at baseline, the diagnosis remained the same in 93% at 6 months. CONCLUSIONS: Concurrent changes in AHI, LVEF, and LVESV were seen after STEMI. Sleep studies performed on admission are reliable in excluding sleep apnea. However, patients with OSA or CSA on admission warrant re-evaluation due to evolution of the sleep apnea phenotype.

Role of Biomarkers in Prediction of Cardiotoxicity During Cancer Treatment.

PURPOSE OF REVIEW: As cancer survivor rates improve with early screening and modern treatment options, cardiotoxicity is becoming an increasing problem. It is imperative for physicians to recognize adverse events early so that appropriate measures can be taken before advanced and permanent cardiac dysfunction ensues. In this review, we will evaluate the literature surrounding current cardiac biomarkers in the detection of cardiotoxicity during cancer treatment as well as discuss the role of emerging novel biomarkers. RECENT FINDINGS: Troponin and brain natriuretic peptides show promise in the detection of subclinical cardiotoxicity during cancer treatment. In addition to identifying late complications among cancer survivors, they have the potential to predict patients who are at risk of developing cardiotoxicity prior to the initiation of cancer therapy. However, there are also conflicting data due to varying study design. Although biomarkers are an attractive option in the detection of cardiotoxicity among cancer patients, current recommendations surrounding its role are based on expert consensus opinion. Further research with appropriately designed prospective trials is required to guide optimal clinical practice.

Watch-PAT versus level III device in diagnosing sleep disordered breathing in first myocardial infarction.

BACKGROUND: Watch-PAT 200, a novel portable sleep device worn on the wrist, has been validated against polysomnography. Although sleep disordered breathing (SDB) screening is recommended in patients with cardiovascular disease, no study has reported a comparison of results from Watch-PAT 200 and level III portable devices. METHODS: Patients (n = 140) admitted with a first ST-segment elevation myocardial infarction (STEMI) participated in a hospital-based sleep study using the Watch-PAT 200 and a level III portable device (Embletta Gold) simultaneously within five days of admission. SDB was defined as an apnea-hypopnea index (AHI) of >15 events/h. RESULTS: The left ventricular ejection fraction was normal (≥50%), impaired (30%-49%) and poor (<30%) in 66 (47.1%), 71 (50.7%), and three (2.2%) patients, respectively. Among 116 patients with a successful paired sleep study, the prevalence of SDB was 53.5% (Watch-PAT 200) and 51.7% (Embletta Gold). The agreement of AHI measured by the two devices was moderately good, with an intra-class correlation value of 0.72 (95% confidence interval, 0.62-0.80; P < .01). Agreement between the two devices in diagnosing at least mild (AHI ≥5), moderate-to-severe (AHI ≥15) and severe (AHI ≥30) SDB was 78% (kappa 0.47; P < .01), 77% (kappa 0.55; P < .01) and 80% (kappa 0.49; P < .01), respectively. At a 15-month follow-up, SDB status based on the two devices was associated with the occurrence of adverse cardiovascular events in 48.3% and 44.8%, respectively (P = .56). CONCLUSION: We found a high prevalence of SDB in patients presenting with a first STEMI. Agreement between two portable sleep devices was moderately good.

Effect of extracellular matrix composition on airway epithelial cell and fibroblast structure: implications for airway remodeling in asthma.

BACKGROUND: Airway remodeling in asthma is characterized by structural changes to the airways including extracellular matrix (ECM) deposition and epithelial metaplasia. Extracellular matrix deposition in the subepithelial region may play an important role in modulation of epithelial cell and fibroblast structure and function because it lies in immediate contact with these cell types and exists within the functional epithelial mesenchymal trophic unit. OBJECTIVE: To investigate the effect of aberrant ECM components on airway epithelial cells and fibroblasts and the relationship among subepithelial ECM deposition, other remodeling changes, and airway hyperresponsiveness. METHODS: BEAS-2B human airway epithelial cells and WI-38 human airway fibroblast cells were cultured on various ECM protein substrates (Matrigel, representing normal basement membrane matrix, or aberrant matrix proteins collagen I, collagen III, and fibronectin). Airway remodeling changes were determined using morphometry in sections from a murine model of chronic allergic airway disease. Airway reactivity to methacholine was determined, and these parameters correlated. RESULTS: Abnormal ECM substrates induced epithelial and fibroblast proliferation and altered the cell morphology of both human airway epithelial cells and fibroblasts when compared with normal basement membrane ECM. Subepithelial matrix deposition in the mouse correlated with epithelial thickness, but only weak correlations were noted among the other parameters. CONCLUSIONS: We have demonstrated that ECM may affect the growth of airway epithelial cells and fibroblasts in vitro and may influence epithelial thickness in the mouse. These findings may have implications for understanding the pathogenesis of asthma and future therapeutic targeting of airway remodeling.