A comprehensive AI-driven analysis of large-scale omic datasets reveals novel dual-purpose targets for the treatment of cancer and aging.

As aging and tumorigenesis are tightly interconnected biological processes, targeting their common underlying driving pathways may induce dual-purpose anti-aging and anti-cancer effects. Our transcriptomic analyses of 16,740 healthy samples demonstrated tissue-specific age-associated gene expression, with most tumor suppressor genes downregulated during aging. Furthermore, a large-scale pan-cancer analysis of 11 solid tumor types (11,303 cases and 4431 control samples) revealed that many cellular processes, such as protein localization, DNA replication, DNA repair, cell cycle, and RNA metabolism, were upregulated in cancer but downregulated in healthy aging tissues, whereas pathways regulating cellular senescence were upregulated in both aging and cancer. Common cancer targets were identified by the AI-driven target discovery platform-PandaOmics. Age-associated cancer targets were selected and further classified into four groups based on their reported roles in lifespan. Among the 51 identified age-associated cancer targets with anti-aging experimental evidence, 22 were proposed as dual-purpose targets for anti-aging and anti-cancer treatment with the same therapeutic direction. Among age-associated cancer targets without known lifespan-regulating activity, 23 genes were selected based on predicted dual-purpose properties. Knockdown of histone demethylase KDM1A, one of these unexplored candidates, significantly extended lifespan in Caenorhabditis elegans. Given KDM1A's anti-cancer activities reported in both preclinical and clinical studies, our findings propose KDM1A as a promising dual-purpose target. This is the first study utilizing an innovative AI-driven approach to identify dual-purpose target candidates for anti-aging and anti-cancer treatment, supporting the value of AI-assisted target identification for drug discovery.

Routine postaccess-closure angiography to detect vascular complications following transfemoral TAVR.

BACKGROUND: Vascular complications following transfemoral TAVR are associated with increased morbidity and mortality. Measures that may mitigate this risk are important. AIM: To evaluate the utility of routine, access-vessel angiography post sheath-removal in the detection and management of complications in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS: This was a retrospective study of 512 consecutive patients who underwent transfemoral TAVR with routine post access-closure angiography from the radial artery. Rates of mild angiographically evident bleeding, bleeding requiring surgery/interventional-radiology, ischemia, 90-day access-site-related events, and major and minor vascular complications using Valve Academic Research Consortium 3 definitions were recorded. RESULTS: Of 512 patients, digital subtraction angiography (DSA) was undertaken via the radial artery in 467 patients (91%). In the remaining patients (9%) DSA was either not attempted, due to concerns regarding kidney disease and contrast volume, or failed due to anatomical factors (aortic tortuosity/calcification). Significant chronic kidney disease was present at baseline in 72.4% of this cohort (stages III-IV or dialysis). Ninety-four percent of cases underwent TAVR using a balloon-expandable platform. Mild iliofemoral extravasation was observed in 7.7% of the DSA cases. These cases were managed by manual compression with none requiring any vascular intervention subsequently. Valve Academic Research Consortium 3 major and minor access-site-related complications were observed in 0.4% and 12.2%, respectively. Access-site-related bleeding and ischemic events requiring interventional-radiology or vascular-surgery were observed in 0.9% and 1.7% of the DSA cases, respectively. No new renal replacement therapy was needed in any of the DSA cases. Discharge to 90-day access-related complications was 0.8%. CONCLUSIONS: Routine post access-closure angiography is feasible via the radial artery in patients undergoing transfemoral TAVR and appears safe. It facilitates early identification of complications and mitigates risk by enabling prompt action to be taken. Larger studies are needed to confirm these findings.

What Are the Causes of Death among Patients Admitted to a Contemporary Tertiary-Level Cardiology Department? An Analysis of 10 Years of Morbidity and Mortality Meetings.

Despite the efforts to deliver the best evidence-based care, in-hospital death is an inevitable event among some patients hospitalized in cardiology departments. We conducted a retrospective evaluation of mortality events from inpatient admissions to the cardiology department between 2010 and 2019. Data were collected from morbidity and mortality meeting presentations that evaluated comorbidities, medical history, treatments, and causes of death for the overall cohort and according to age group and sex. There were 1182 registered deaths. The most common causes of death among patients were acute myocardial infarction (AMI, 53.0%), heart failure (HF, 11.7%), cardiac arrest (CA, 6.6%), HF with complication/defined cardiomyopathy (6.3%), and sepsis (4.4%). We observed a decline in deaths from AMI from 61.9% in 2010 to 46.7% in 2019, while there was a clear increase in deaths from HF (11.1% in 2010 to 25.9% in 2019). Compared to patients ≥65 years, younger patients were more likely to have died from CA (15.7% vs. 4.3%, p < 0.001) and other cardiac reasons (3.0% vs. 0.4%, p < 0.001). The majority of deaths were due to AMI, HF, and CA. We observed a significant declining trend in the proportion of deaths due to AMI in recent years, with an increase in deaths due to HF.

PARP14 inhibition restores PD-1 immune checkpoint inhibitor response following IFNγ-driven acquired resistance in preclinical cancer models.

Resistance mechanisms to immune checkpoint blockade therapy (ICBT) limit its response duration and magnitude. Paradoxically, Interferon γ (IFNγ), a key cytokine for cellular immunity, can promote ICBT resistance. Using syngeneic mouse tumour models, we confirm that chronic IFNγ exposure confers resistance to immunotherapy targeting PD-1 (α-PD-1) in immunocompetent female mice. We observe upregulation of poly-ADP ribosyl polymerase 14 (PARP14) in chronic IFNγ-treated cancer cell models, in patient melanoma with elevated IFNG expression, and in melanoma cell cultures from ICBT-progressing lesions characterised by elevated IFNγ signalling. Effector T cell infiltration is enhanced in tumours derived from cells pre-treated with IFNγ in immunocompetent female mice when PARP14 is pharmacologically inhibited or knocked down, while the presence of regulatory T cells is decreased, leading to restoration of α-PD-1 sensitivity. Finally, we determine that tumours which spontaneously relapse in immunocompetent female mice following α-PD-1 therapy upregulate IFNγ signalling and can also be re-sensitised upon receiving PARP14 inhibitor treatment, establishing PARP14 as an actionable target to reverse IFNγ-driven ICBT resistance.

The role of IFN-γ-signalling in response to immune checkpoint blockade therapy.

Treatment with immune checkpoint inhibitors, widely known as immune checkpoint blockade therapy (ICBT), is now the fourth pillar in cancer treatment, offering the chance of durable remission for patients with advanced disease. However, ICBT fails to induce objective responses in most cancer patients with still others progressing after an initial response. It is necessary, therefore, to elucidate the primary and acquired resistance mechanisms to ICBT to improve its efficacy. Here, we highlight the paradoxical role of the cytokine interferon-γ (IFN-γ) in ICBT response: on the one hand induction of IFN-γ signalling in the tumour microenvironment correlates with good ICBT response as it drives the cellular immune responses required for tumour destruction; nonetheless, IFN-γ signalling is implicated in ICBT acquired resistance. We address the negative feedback and immunoregulatory effects of IFN-γ signalling that promote immune evasion and resistance to ICBT and discuss how these can be targeted pharmacologically to restore sensitivity or circumvent resistance.

The Dysregulation of MicroRNAs in the Development of Cervical Pre-Cancer-An Update.

Globally in 2020, an estimated ~600,000 women were diagnosed with and 340,000 women died from cervical cancer. Compared to 2012, the number of cases increased by 7.5% and the number of deaths increased by 17%. MiRNAs are involved in multiple processes in the pathogenesis of cervical cancer. Dysregulation of miRNAs in the pre-stage of cervical cancer is the focus of this review. Here we summarize the dysregulated miRNAs in clinical samples from cervical pre-cancer patients and relate them to the early transformation process owing to human papillomavirus (HPV) infection in the cervical cells. When HPV infects the normal cervical cells, the DNA damage response is initiated with the involvement of HPV's E1 and E2 proteins. Later, cell proliferation and cell death are affected by the E6 and E7 proteins. We find that the expressions of miRNAs in cervical pre-cancerous tissue revealed by different studies seldom agreed with each other. The discrepancy in sample types, samples' HPV status, expression measurement, and methods for analysis contributed to the non-aligned results across studies. However, several miRNAs (miR-34a, miR-9, miR-21, miR-145, and miR-375) were found to be dysregulated across multiple studies. In addition, there are hints that the DNA damage response and cell growth response induced by HPV during the early transformation of the cervical cells are related to these miRNAs. Currently, no review articles analyse the relationship between the dysregulated miRNAs in cervical pre-cancerous tissue and their possible roles in the early processes involving HPV's protein encoded by the early genes and DNA damage response during normal cell transformation. Our review provides insight on spotting miRNAs involved in the early pathogenic processes and pointing out their potential as biomarker targets of cervical pre-cancer.

Misdiagnosis of aortic dissection: A systematic review of the literature.

BACKGROUND: Aortic dissection is a rare but potentially catastrophic condition. Misdiagnosis of aortic dissection is not uncommon as symptoms can overlap with other diagnoses. OBJECTIVE: We conducted a systematic review to better understand the factors contributing to incorrect diagnosis of this condition. METHODS: We searched MEDLINE and EMBASE for studies that evaluated the misdiagnosis of aortic dissection. The rate of misdiagnosis was pooled and results were narratively synthesized. RESULTS: A total of 12 studies with were included with 1663 patients. The overall rate of misdiagnosis of aortic dissection was 33.8%. The proportion of patients presenting with chest pain, back pain and syncope were 67.5%, 24.8% and 6.8% respectively. The proportion of patients with pre-existing hypertension was 55.4%, 30.5% were smokers while the proportion of patients with coronary artery disease, previous cardiovascular surgery or surgical trauma and Marfan syndrome was 14.7%, 5.8%, and 3.7%, respectively. Factors related to misdiagnosis included the presence of symptoms and features associated with other diseases (such as acute coronary syndrome, stroke and pulmonary embolism), the absence of typical features (such as widened mediastinum on chest X-ray) or concurrent conditions such congestive heart failure. Factors associated with more accurate diagnosis included more comprehensive history taking and increased use of imaging. CONCLUSIONS: Misdiagnosis in patients with an eventual diagnosis of aortic dissection affects 1 in 3 patients. Clinicians should consider aortic dissection as differential diagnosis in patients with chest pain, back pain and syncope. Imaging should be used early to make the diagnosis when aortic dissection is suspected.

Smoking cessation after acute coronary syndrome: A systematic review and meta-analysis.

BACKGROUND: Smoking cessation is an effective secondary prevention measure after acute coronary syndrome (ACS). We conducted a systematic review with the aim to better understand which patients have a greater propensity to quit smoking and the risk factors for continued smoking after ACS. METHODS: We searched MEDLINE and EMBASE for studies that evaluated smoking cessation after ACS. The pooled rate of smoking cessation across included studies was performed. Random effects meta-analysis for different variables and their association with smoking cessation was conducted. RESULTS: A total of 39 studies with 11 228 patients were included in this review. The pooled rate of smoking cessation following ACS across 38 studies was 45.0%. Factors associated with greater likelihood of smoking cessation were attendance at cardiac rehabilitation (OR 1.90 95% CI 1.44-2.51), married/not alone (OR 1.68 95% CI 1.32-2.13), intention/attempt to quit smoking (OR 1.27 95% CI 1.11-1.46), diabetes mellitus (OR 1.24 95% CI 1.03-1.51) and hospitalised duration (OR 1.09 95% CI 1.02-1.15). Variables associated with a lower likelihood of smoking cessation were depression (OR 0.57 95% CI 0.43-0.75), chronic obstructive pulmonary disease/lung disease (OR 0.73 95% CI 0.57-0.93), previous admission with acute myocardial infarction/cardiac admission (OR 0.61 95% CI 0.47-0.80), cerebrovascular disease/transient ischaemic attack (OR 0.42 95% CI 0.30-0.58) and unemployment (OR 0.37 95% CI 0.17-0.80). CONCLUSIONS: The majority of smokers with an ACS continue to smoke after admission. Patients attending cardiac rehabilitation show increased odds of quitting while people who are depressed and those with chronic lung disease were less likely to quit smoking and should be targeted for intensive smoking cessation interventions.

Misdiagnosis of Heart Failure: A Systematic Review of the Literature.

BACKGROUND: Heart failure (HF) is a chronic disease associated with a significant burden to patients, families, and health services. The diagnosis of HF can be easily missed owing to similar symptoms with other conditions especially respiratory diseases. METHODS AND RESULTS: We conducted a systematic review to determine the rates of HF and cardiomyopathy misdiagnosis and explored the potential causes. The included studies were narratively synthesized. Ten studies were identified including a total of 223,859 patients. There was a lack of definition of HF misdiagnosis in the studies and inconsistent diagnostic criteria were used. The rates of HF misdiagnosis ranged from 16.1% in hospital setting to 68.5% when general practitioner referred patients to specialist setting. The most common cause for misdiagnosis was chronic obstructive pulmonary disease (COPD). One study using a COPD cohort showed that HF was unrecognized in 20.5% of patients and 8.1% had misdiagnosis of HF as COPD. Another study suggests that anemia and chronic kidney disease are associated with an increase in the odds of unrecognized left ventricular systolic dysfunction. Other comorbidities such as obesity, old age, atrial fibrillation, and ischemic heart disease are prevalent in patients with a misdiagnosis of HF. CONCLUSIONS: The misdiagnosis of HF is an unfortunate part of everyday clinical practice that occurs with a variable rate depending on the population studied. HF is frequently misdiagnosed as COPD. More research is needed to better understand the missed opportunities to correctly diagnose HF so that harm to patients can be avoided and effective treatments can be implemented.

The role of the Tei index in assessing for cardiotoxicity from anthracycline chemotherapy: a systematic review.

BACKGROUND: Anthracycline agents are known to be effective in treating tumors and hematological malignancies. Although these agents improve survival, their use is associated with cardiotoxic effects, which most commonly manifests as left ventricular systolic dysfunction (LVSD). As such, guidelines recommend the periodic assessment of left ventricular ejection fraction (LVEF). However, as diastolic dysfunction likely proceeds systolic impairment in this setting, the role of Tei index may offer additional benefit in detecting subclinical LVSD. METHODS: We conducted a systematic review to investigate the evidence for the use of Tei index in assessing subclinical cardiotoxicity in patients receiving anticancer agents. A search of Medline and EMBASE was performed and relevant studies were reviewed and narratively synthesized. RESULTS: A total of 13 studies were included with a total of 800 patients (mean age range 46-62 years, percentage of male participants ranged from 0-86.9%). An increase in Tei index was observed in 11 studies, which suggested a decline in cardiac function following chemotherapy. Out of these, six studies indicated that the Tei index is a useful parameter in predicting cardiotoxic LVSD. Furthermore, five studies indicated Tei index to be superior to LVEF in detecting subclinical cardiotoxicity. CONCLUSIONS: Though there are some studies that suggest that Tei index may be a useful indicator in assessing subclinical anthracycline-related cardiotoxicity, the findings are inconsistent and so more studies are needed before the evaluation of Tei index is performed routinely in patients receiving chemotherapy.

Percutaneous coronary intervention in patients with cancer and readmissions within 90 days for acute myocardial infarction and bleeding in the USA.

AIMS: The post-discharge outcomes of patients with cancer who undergo PCI are not well understood. This study evaluates the rates of readmissions within 90 days for acute myocardial infarction (AMI) and bleeding among patients with cancer who undergo percutaneous coronary intervention (PCI). METHODS AND RESULTS: Patients treated with PCI in the years from 2010 to 2014 in the US Nationwide Readmission Database were evaluated for the influence of cancer on 90-day readmissions for AMI and bleeding. A total of 1 933 324 patients were included in the analysis (2.7% active cancer, 6.8% previous history of cancer). The 90-day readmission for AMI after PCI was higher in patients with active cancer (12.1% in lung, 10.8% in colon, 7.5% in breast, 7.0% in prostate, and 9.1% for all cancers) compared to 5.6% among patients with no cancer. The 90-day readmission for bleeding after PCI was higher in patients with active cancer (4.2% in colon, 1.5% in lung, 1.4% in prostate, 0.6% in breast, and 1.6% in all cancer) compared to 0.6% among patients with no cancer. The average time to AMI readmission ranged from 26.7 days for lung cancer to 30.5 days in colon cancer, while the average time to bleeding readmission had a higher range from 38.2 days in colon cancer to 42.7 days in breast cancer. CONCLUSIONS: Following PCI, patients with cancer have increased risk for readmissions for AMI or bleeding, with the magnitude of risk depending on both cancer type and the presence of metastasis.

Location of death among patients presenting with cardiovascular disease to the emergency department in the United states.

BACKGROUND: In-hospital deaths are an important outcome and little is known about deaths in the emergency department (ED). Among patients who died of cardiovascular diseases (CVD), we assessed causes of death, temporal trends and the relative distribution of deaths in the ED versus hospital. METHODS: Using the United States Nationwide Emergency Department Sample, we conducted a retrospective study of patients presenting to the ED with a primary diagnosis of CVD between 2006 and 2014. We used descriptive statistics to describe causes of deaths, temporal trends and location of death. RESULTS: During the study period, there were 27 144 508 visits to the ED with CVD diagnoses (~2% of all ED visits,). The most common CVD diagnoses were heart failure (n = 8 571 598), acute myocardial infarction (n = 4 827 518) and atrial fibrillation/flutter (n = 4 713 241). There were a total of 2.2 million deaths caused by the CVD, with the majority (57.6%) occurring in the ED. Cardiac arrest was the most common cause of in-hospital death (n = 1 225 095, 55.3%), followed by acute myocardial infarction (n = 279 310, 12.6%), heart failure (n = 217 367, 9.8%), intracranial hemorrhage (n = 168 009, 7.6%) and ischemic stroke (n = 151 615, 6.8%). The proportion of deaths in the ED for these causes were 91.9% cardiac arrest (n = 1 173 471), 3.6% acute myocardial infarction (n = 46 909), 1.0% heart failure (n = 12 599) and 1.1% intracranial hemorrhage (n = 13 579). There was a decrease in death for most CVDs over time. CONCLUSIONS: Inpatient CVD admissions and their associated death may not be a robust measure of the national burden of CVD since ED death-which are common for some conditions-are not captured.

Deep learning model for prediction of extended-spectrum beta-lactamase (ESBL) production in community-onset Enterobacteriaceae bacteraemia from a high ESBL prevalence multi-centre cohort.

Adequate empirical antimicrobial coverage is instrumental in clinical management of community-onset Enterobacteriaceae bacteraemia in areas with high ESBL prevalence, while balancing the risk of carbapenem overuse and emergence of carbapenem-resistant organisms. It is unknown whether machine learning offers additional advantages to conventional statistical methods in prediction of ESBL production. To develop a validated model to predict ESBL production in Enterobacteriaceae causing community-onset bacteraemia. 5625 patients with community-onset bacteraemia caused by Escherichia coli, Klebsiella species and Proteus mirabilis during 1 January 2015-31 December 2019 from three regional hospitals in Hong Kong were included in the analysis, after exclusion of blood cultures obtained beyond 48 h of admission. The prevalence of ESBL-producing Enterobacteriaceae was 23.7% (1335/5625). Deep neural network and other machine learning algorithms were compared against conventional statistical model via multivariable logistic regression. Primary outcomes compared consisted of predictive model area under curve of receiver-operator characteristic curve (AUC), and macro-averaged F1 score. Secondary outcomes included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Deep neural network yielded an AUC of 0.761 (95% CI 0.725-0.797) and F1 score of 0.661 (95% CI 0.633-0.689), which was superior to logistic regression (AUC 0.667 (95% CI 0.627-0.707), F1 score 0.596 (95% CI 0.567-0.625)). Deep neural network had a specificity of 91.5%, sensitivity of 37.5%, NPV of 82.5%, and PPV of 57.9%. Deep neural network is superior to logistic regression in predicting ESBL production in Enterobacteriaceae causing community-onset bacteraemia in high-ESBL prevalence area. Machine learning offers clinical utility in guiding judicious empirical antibiotics use.

Effectiveness of Scutellaria barbata water extract on inhibiting colon tumor growth and metastasis in tumor-bearing mice.

The plant Scutellaria barbata (SB) is commonly used as herbal medicines for treating cancer. The present pre-clinical study aimed to validate the Chinese Pharmacopoeia (CP) recommended dosages of SB water extract (SBW) in treating colon tumors. The content of chemical marker scutellarin in SBW was quantified using UPLC. Mice bearing human HCT116 xenografts or murine colon26 tumors received oral administration of SBW or scutellarin for 4 weeks. Results showed that SBW (615 and 1,230 mg/kg) and scutellarin (7 mg/kg) treatments significantly reduced human xenograft weights by 28.7, 36.9 and 28.8%, respectively. Lung metastasis area could be ameliorated after SBW (615 mg/kg) and scutellarin (7 mg/kg) treatments by 23.4 and 29.5%, respectively. Expressions of colon cancer metastasis-related proteins E-cadherin, Tspan 8 and CXCR4, as well as Src kinase in tumors were first shown to be regulated by SBW. Furthermore, in murine colon26 tumor-bearing mice, SBW (615 mg/kg) and scutellarin (7 mg/kg) treatments reduced the orthotopic tumor burden by 94.7% and lung metastatic tumor burden by 94.1%, respectively. Our findings provided evidences that SBW (at the mouse equivalent dosages to clinical dosages recommended by CP) could exert anti-tumor and anti-metastatic effects in colon cancer animal models.

Clinical features and outcomes of adults with coronavirus disease 2019: A systematic review and pooled analysis of the literature.

BACKGROUND: The 2019 coronavirus disease (COVID-19) has become a global pandemic and the published literature describing the virus has grown exponentially. METHODS: We conducted a systematic review of the literature to identify the symptoms, comorbidities present, radiological features and outcomes for adults testing positive for COVID-19 admitted to hospital. The results across multiple studies were numerically pooled to yield total estimated. RESULTS: A total of 45 studies were included in this review with 14 358 adult participants (average age 51 years, male 51%). The pooled findings suggest that the most common symptom among patients was fever (81.2%) followed by cough (62.9%), fatigue (38.0%) and anorexia/loss of appetite (33.7%). The comorbidities that were most prevalent among patients with the virus were hypertension (19.1%), cardiovascular disease (17.9%), endocrine disorder (9.3%) and diabetes (9.2%). Abnormal chest X-ray findings were present in 27.7% of patients and ground-glass opacity was demonstrated on chest computerized tomography in 63.0% of patients. The most frequent adverse outcomes were acute respiratory distress syndrome (27.4%), acute cardiac injury (16.2%) and acute kidney injury (12.6%). Death occurred in 8.2% of patients and 16.3% required intensive care admission and 11.7% had mechanical ventilation. Bacterial or secondary infections affected 8.5% of patients and 6.9% developed shock. CONCLUSIONS: COVID-19 most commonly presents with fever, cough, fatigue and anorexia and among patients with existing hypertension and cardiovascular disease. It is important as serious adverse outcomes can develop such as acute respiratory distress syndrome, acute cardiac injury, acute kidney injury and death.

Cardiac arrest and related mortality in emergency departments in the United States: Analysis of the nationwide emergency department sample.

AIMS: The aim of this study is to analyse the causes of cardiac arrests (CA) in the emergency departments (ED) in the United States and their clinical outcomes according to whether they had a primary or a secondary diagnosis of CA. METHODS: Data from the Nationwide Emergency Department Sample was assessed for episodes of CA in the emergency department (ED) for adults from 2006 to 2014. Primary and secondary diagnoses of CA and mortality outcomes were evaluated in ED, inpatient and the combined in-hospital setting. RESULTS: There were 2,852,347 ED episodes with a diagnosis of CA (50.5% primary diagnosis, 49.5% secondary diagnosis). Among patients with a secondary diagnosis of CA, ∼33% patients had a primary cardiac diagnosis, followed by infectious and respiratory diagnoses. The survival to ED discharge was 53.2%; lower for primary versus secondary CA diagnosis (20.4% vs 86.7%). The in-hospital survival rate for all CA was 28.7%, and was lower for primary versus secondary CA diagnosis (15.7% vs 41.9%). Survival to hospital discharge was highest in the age group of 41-60 years (33.0%) and was least among >80 years (20.9%). Survival was also noted to be lower among female patients (27.9% vs 29.2%) and in the winter months. CONCLUSIONS: Survival with CA in ED is <30% of patients and is greater among patients with a secondary diagnosis of CA. CAs are associated with significant mortality in ED and hospital settings and measures should be taken to better manage cardiac, infection and respiratory causes particularly in the winter months.

The prognostic value of Tei index in acute myocardial infarction: a systematic review.

BACKGROUND: Echocardiographic evaluation of left ventricular ejection fraction (LVEF) is used in the risk stratification of patients with an acute myocardial infarction (AMI). However, the prognostic value of the Tei index, an alternative measure of global cardiac function, in AMI patients is not well established. METHODS: We conducted a systematic review, using MEDLINE and EMBASE, to evaluate the prognostic value of the Tei index in predicting adverse outcomes in patients presenting with AMI. The data was collected and narratively synthesised. RESULTS: A total of 16 studies were including in this review with 2886 participants (mean age was 60 years from 14 studies, the proportion of male patients 69.8% from 14 studies). Patient follow-up duration ranged from during the AMI hospitalisation stay to 57.8 months. Tei index showed a significant association with heart failure episodes, reinfarction, death and left ventricular thrombus formation in 14 out of the 16 studies. However, in one of these studies, Tei index was only significantly predictive of cardiac events in patients where LVEF was <40%. In two further studies, Tei index was not associated with predicting adverse outcomes once LVEF, left ventricular end-systolic volume index and left ventricular early filling time was taken into consideration. In the two remaining studies, there was no prognostic value of Tei index in relation to patient outcomes. CONCLUSIONS: Tei index may be an important prognostic marker in AMI patients, however, more studies are needed to better understand when it should be used routinely within clinical practice.

A systematic review of the studies that evaluate the performance of the DAPT score.

BACKGROUND: The Dual Antiplatelet Therapy (DAPT) score was derived to determine which patients may benefit from prolonged DAPT therapy after 12 months based on the balance between ischaemic and bleeding events. Several studies have attempted to validate the score with inconsistent findings. METHODS: We conducted a systematic review of the studies that evaluated the DAPT score in PCI populations. A search was performed on MEDLINE and EMBASE and two independent reviewers reviewed the search results for study inclusion and extracted data from studies which met the inclusion criteria. Data are presented in tables and narrative synthesis was performed. RESULTS: A total of 13 studies were included in this review. The study designs included post hoc analysis of randomised trials, prospective cohorts, retrospective cohorts and a case-control study. In the derivation/validation study, the c-statistic for ischaemic and bleeding outcomes were 0.64/0.70 and 0.68/0.64, respectively. Among the validation studies, the C-statistics for composite outcomes ranged from 0.53 to 0.71 for ischaemic outcomes and 0.49 to 0.71 for bleeding outcomes. Only one study randomised patients with high DAPT score to different combinations of antiplatelet after 1 year of DAPT and found that continuation of DAPT was associated with fewer deaths because of myocardial infarction, but more bleeding. CONCLUSIONS: While not designed for this purpose many studies have shown that the DAPT score has modest predictive value for ischaemic and bleeding outcomes. A prospective randomised controlled trial is needed to evaluate the clinical benefits of utilising the DAPT score in guiding continued DAPT therapy beyond 1 year.

Topical application of Chinese herbal medicine DAEP relieves the osteoarthritic knee pain in rats.

BACKGROUND: The potential adverse effects of conventional oral pharmacotherapy of osteoarthritis (OA) restrict their long-term use. Topical application of a Chinese herbal paste for relieving OA knee pain can be effective and safe. However, evidence-based scientific research is insufficient to support its application worldwide. The aim of this study was to investigate the in vivo efficacy of a topical Chinese herbal paste on relieving OA knee pain and its underlying mechanism. METHODS: An OA rat model was developed by anterior cruciate ligament transection (ACLT) followed by treadmill running. A herbal paste including Dipsaci Radix, Achyranthis Bidentatae Radix, Eucommiae Cortex and Psoraleae Fructus, named as DAEP, was applied topically on the knee joint of the rats (DAEP). The rats without DAEP treatment served as Control. Rats with surgery but without ACLT, treadmill running and DAEP treatment acted as Sham. The morphologic change of the knee joint was observed radiographically. Nociception from the knee of the rats was assessed using Incapacitent test and CatWalk gait system. The therapeutic mechanism was investigated by analyzing the gene and protein expression of inflammatory markers via qPCR and Western blot, respectively. RESULTS: Radiographic images showed less destruction at the posterior tibial plateau of the DAEP group compared with the Control after 2 weeks of treatment. The static weight ratio and the gait parameters of the Control were reduced significantly via Incapacitance test and CatWalk gait analysis, respectively. DAEP treatment increased the Print Area and Maximum Intensity significantly compared with the Control. DAEP significantly suppressed the upregulation of gene expression of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS). CONCLUSIONS: DAEP exhibited its effect via the nuclear factor (NF)-κB pathway by suppressing the phosphorylation of IκB kinase αß (p-IKKαß) and cyclooxygenase-2 (COX-2) protein expression. This study provides scientific evidence to support the clinical application of the Chinese herbal paste on reliving OA pain.