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1.
Ann Acad Med Singap ; 53(1): 23-33, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38920212

RESUMO

Introduction: In 2022, the Minister for Health of Singapore launched Healthier SG, a national strategy in championing the shift towards a population health approach. Method: The Singapore Heart Foundation conducted a series of roundtable discussions, also attended by representatives of the Singapore Cardiac Society and the Chapter of Cardiologists of the Academy of Medicine Singapore. During the meetings, the authors formulated interventions supportive of Healthier SG that specifically aimed to uplift the state of cardiovascular (CV) preventive care in Singapore. Results: In line with Healthier SG, the authors propose a 3-pronged approach ("Healthier Heart SG") to augment the success of Healthier SG in achieving good CV outcomes. This proposal includes the following components: (1) a call to update the standards of care in addressing the 5 main modifiable risk factors of cardiovascular disease (CVD); (2) patient education through cooperation between healthcare professionals and community partners for a whole-of-system approach; and (3) support for integrated care, including access to cardiac rehabilitation in the community, improved referral processes and access to nutrition/dietetics counselling and tobacco cessation, optimal use of information technology, and continued CV research. Conclusion: Healthier Heart SG would bring the standards of care and CV care delivery in Singapore closer to achieving the vision of proactive prevention of CVD and CV morbidity and mortality. This can only be achieved through the concerted efforts of healthcare professionals, policymakers and community partners, coupled with the cooperation of community members.


Assuntos
Doenças Cardiovasculares , Sociedades Médicas , Singapura/epidemiologia , Humanos , Doenças Cardiovasculares/prevenção & controle , Cardiologia/organização & administração , Educação de Pacientes como Assunto , Reabilitação Cardíaca/métodos , Fundações/organização & administração , Fatores de Risco de Doenças Cardíacas
2.
Postgrad Med J ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899828

RESUMO

BACKGROUND: The utilization of postdilatation in primary percutaneous coronary intervention (PCI) is feared to induce suboptimal coronary blood flow and compromise the outcome of the patients. This meta-analysis sought to verify whether postdilatation during primary PCI is associated with worse angiographic or long-term clinical outcomes. METHODS: Systematic literature searches were conducted on PubMed, The Cochrane Library, ClinicalTrials.gov, EBSCO, and Europe PMC on 10 March 2024. Eligible studies reporting the outcomes of postdilatation among ST-segment elevation myocardial infarction patients were included. The primary outcome was no-reflow condition during primary PCI based on angiographic finding. The secondary clinical outcome was major adverse cardiovascular events (MACEs) comprising all-cause death, myocardial infarction, target vessel revascularization (TVR), and stent thrombosis. RESULTS: Ten studies were finally included in this meta-analysis encompassing 3280 patients, which was predominantly male (76.6%). Postdilatation was performed in 40.7% cases. Postdilatation was associated with increased risk of no-reflow during primary PCI [Odd Ratio (OR) = 1.33, 95% Confidence Interval (CI): 1.12-1.58; P = .001)]. Conversely, postdilatation had a tendency to reduce MACE (OR = 0.70, 95% CI: 0.51-0.97; P = .03) specifically in terms of TVR (OR = 0.41, 95% CI: 0.22-0.74; P = .003). No significant differences between both groups in relation to mortality (OR = 0.58, 95% CI: 0.32-1.05; P = .07) and myocardial infarction (OR = 1.5, 95% CI: 0.78-2.89; P = .22). CONCLUSIONS: Postdilatation after stent deployment during primary PCI appears to be associated with an increased risk of no-reflow phenomenon after the procedure. Nevertheless, postdilatation strategy has demonstrated a significant reduction in MACE over the course of long-term follow-up. Specifically, postdilatation significantly decreased the occurrence of TVR. Key messages: What is already known on this topic?  Optimizing stent deployment by performing postdilatation during percutaneous coronary intervention (PCI) is essential for long-term clinical outcomes. However, its application during primary PCI is controversial due to the fact that it may provoke distal embolization and worsen coronary blood flow. What this study adds?  In this systematic review and meta-analysis of 10 studies, we confirm that postdilatation during primary PCI is associated with worse coronary blood flow immediately following the procedure. On the contrary, this intervention proves advantageous in improving long-term clinical outcomes, particularly in reducing target vessel revascularization. How this study might affect research, practice, or policy?  Given the mixed impact of postdilatation during primary PCI, this strategy should only be applied selectively. Future research should focus on identifying patients who may benefit from such strategy.

3.
Expert Rev Cardiovasc Ther ; 22(6): 203-215, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38739469

RESUMO

INTRODUCTION: Anticoagulants play a vital role as part of the antithrombotic therapy of myocardial infarction and are complementary to antiplatelet therapies. In the acute setting, the rationale for their use is to antagonize the ongoing clotting cascade including during percutaneous coronary intervention. Anticoagulation may be an important part of the longer-term antithrombotic strategy especially in patients who have other existing indications (e.g. atrial fibrillation) for their use. AREAS COVERED: In this narrative review, the authors provide a contemporary summary of the anticoagulation strategies of patients presenting with NSTEMI, both in terms of anticoagulation during the acute phase as well as suggested antithrombotic regimens for patients who require long-term anticoagulation for other indications. EXPERT OPINION: Patients presenting with non-ST-elevation myocardial infarction (NSTEMI) should be initiated on anticoagulation (e.g. heparin/low molecular weight heparin) for the initial hospitalization period for those medically managed or until percutaneous coronary intervention. Longer term management of NSTEMI for patients with an existing indication for long-term anticoagulation should comprise triple antithrombotic therapy of anticoagulant (preferably DOAC) with aspirin and clopidogrel for up to 1 month (typically 1 week or until hospital discharge), followed by DOAC plus clopidogrel for up to 1 year, and then DOAC monotherapy thereafter.


Assuntos
Anticoagulantes , Fibrinolíticos , Infarto do Miocárdio sem Supradesnível do Segmento ST , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Humanos , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/administração & dosagem , Infarto do Miocárdio sem Supradesnível do Segmento ST/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Fibrinolíticos/administração & dosagem , Quimioterapia Combinada , Fatores de Tempo
4.
Circulation ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38742915

RESUMO

Background: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarct (MI) size in the pre-clinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction (MVO) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Methods: This was a Phase 2, multi-center, randomized, double-blind, placebo controlled clinical trial conducted between November 2017 to November 2021 in six cardiac centers in Singapore (NCT03102723). Patients were randomized to receive either cangrelor or placeboinitiated prior to the PPCI procedure on top of oral ticagrelor. The key exclusion criteria included: presenting <6 hours of symptom onset, prior MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance (CMR). The primary efficacy endpoint was acute MI size by CMR within the first week expressed as percentage of the left ventricle mass ( %LVmass). MVO was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety endpoint was Bleeding Academic Research Consortium (BARC)-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test [reported as median (1st quartile- 3rd quartile)] and categorical variables were compared by Fisher's exact test. A 2-sided P<0.05 was considered statistically significant. Results: Of 209 recruited patients, 164 patients (78% ) completed the acute CMR scan. There were no significant differences in acute MI size [placebo: 14.9 (7.3 - 22.6) %LVmass versus cangrelor: 16.3 (9.9 - 24.4)%LVmass, P=0.40] or the incidence [placebo: 48% versus cangrelor: 47%, P=0.99] and extent of MVO [placebo:1.63 (0.60 - 4.65)%LVmass versus cangrelor: 1.18 (0.53 - 3.37)%LVmass, P=0.46] between placebo and cangrelor despite a two-fold decrease in platelet reactivity with cangrelor. There were no BARC-defined major bleeding events in either group in the first 48 hours. Conclusions: Cangrelor administered at time of PPCI did not reduce acute MI size or prevent MVO in STEMI patients given oral ticagrelor despite a significant reduction of platelet reactivity during the PCI procedure.

5.
Eur Heart J Open ; 4(2): oeae025, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38659665

RESUMO

Aims: Aging-related cardiovascular disease and frailty burdens are anticipated to rise with global aging. In response to directions from major cardiovascular societies, we investigated frailty knowledge, awareness, and practices among cardiologists as key stakeholders in this emerging paradigm a year after the European Frailty in Cardiology consensus document was published. Methods and results: We launched a prospective multinational web-based survey via social networks to broad cardiology communities representing multiple World Health Organization regions, including Western Pacific and Southeast Asia regions. Overall, 578 respondents [38.2% female; ages 35-49 years (55.2%) and 50-64 years (34.4%)] across subspecialties, including interventionists (43.3%), general cardiologists (30.6%), and heart failure specialists (HFSs) (10.9%), were surveyed. Nearly half had read the consensus document (38.9%). Non-interventionists had better perceived knowledge of frailty assessment instruments (fully or vaguely aware, 57.2% vs. 45%, adj. P = 0.0002), exercise programmes (well aware, 12.9% vs. 6.0%, adj. P = 0.001), and engaged more in multidisciplinary team care (frequently or occasionally, 52.6% vs. 41%, adj. P = 0.002) than interventionists. Heart failure specialists more often addressed pre-procedural frailty (frequently or occasionally, 43.5% vs. 28.2%, P = 0.004) and polypharmacy (frequently or occasionally, 85.5% vs. 71%, adj. P = 0.014) and had consistently better composite knowledge (39.3% vs. 21.6%, adj. P = 0.001) and practice responses (21% vs. 11.1%, adj. P = 0.018) than non-HFSs. Respondents with better knowledge responses also had better frailty practices (40.3% vs. 3.6%, adj. P < 0.001). Conclusion: Distinct response differences suggest that future strategies strengthening frailty principles should address practices peculiar to subspecialties, such as pre-procedural frailty strategies for interventionists and rehabilitation interventions for HFSs.

6.
J Thromb Thrombolysis ; 57(3): 408-417, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38300500

RESUMO

This study aim to investigate if remote intensive coaching for the first 6 months post-AMI will improve adherence to the twice-a-day antiplatelet medication, ticagrelor. Between July 8, 2015, to March 29, 2019, AMI patients were randomly assigned to remote intensive management (RIM) or standard care (SC). RIM participants underwent 6 months of weekly then two-weekly consultations to review medication side effects and medication adherence coaching by a centralized nurse practitioner team, whereas SC participants received usual cardiologist face-to-face consultations. Adherence to ticagrelor were determined using pill counting and serial platelet reactivity measurements for 12 months. A total of 149 (49.5%) of participants were randomized to RIM and 152 (50.5%) to SC. Adherence to ticagrelor was similar between RIM and SC group at 1 month (94.4 ± 0.7% vs. 93.6±14.7%, p = 0.537), 6 months (91.0±14.6% vs. 90.6±14.8%, p = 0.832) and 12 months (87.4±17.0% vs. 89.8±12.5%, p = 0.688). There was also no significant difference in platelet reactivity between the RIM and SC groups at 1 month (251AU*min [212-328] vs. 267AU*min [208-351], p = 0.399), 6 months (239AU*min [165-308] vs. 235AU*min [171-346], p = 0.610) and 12 months (249AU*min [177-432] vs. 259AU*min [182-360], p = 0.678). Sensitivity analysis did not demonstrate any association of ticagrelor adherence with bleeding events and major adverse cardiovascular events. RIM, comprising 6 months of intensive coaching by nurse practitioners, did not improve adherence to the twice-a-day medication ticagrelor compared with SC among patients with AMI. A gradual decline in ticagrelor adherence over 12 months was observed despite 6 months of intensive coaching.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Ticagrelor/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/induzido quimicamente , Inibidores da Agregação Plaquetária/uso terapêutico , Plaquetas , Hemorragia/induzido quimicamente , Resultado do Tratamento
7.
Lancet Reg Health West Pac ; 37: 100803, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37693863

RESUMO

Background: Understanding the trajectories of metabolic risk factors for acute myocardial infarction (AMI) is necessary for healthcare policymaking. We estimated future projections of the incidence of metabolic diseases in a multi-ethnic population with AMI. Methods: The incidence and mortality contributed by metabolic risk factors in the population with AMI (diabetes mellitus [T2DM], hypertension, hyperlipidemia, overweight/obesity, active/previous smokers) were projected up to year 2050, using linear and Poisson regression models based on the Singapore Myocardial Infarction Registry from 2007 to 2018. Forecast analysis was stratified based on age, sex and ethnicity. Findings: From 2025 to 2050, the incidence of AMI is predicted to rise by 194.4% from 482 to 1418 per 100,000 population. The largest percentage increase in metabolic risk factors within the population with AMI is projected to be overweight/obesity (880.0% increase), followed by hypertension (248.7% increase), T2DM (215.7% increase), hyperlipidemia (205.0% increase), and active/previous smoking (164.8% increase). The number of AMI-related deaths is expected to increase by 294.7% in individuals with overweight/obesity, while mortality is predicted to decrease by 11.7% in hyperlipidemia, 29.9% in hypertension, 32.7% in T2DM and 49.6% in active/previous smokers, from 2025 to 2050. Compared with Chinese individuals, Indian and Malay individuals bear a disproportionate burden of overweight/obesity incidence and AMI-related mortality. Interpretation: The incidence of AMI is projected to continue rising in the coming decades. Overweight/obesity will emerge as fastest-growing metabolic risk factor and the leading risk factor for AMI-related mortality. Funding: This research was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03) and National Medical Research Council Research Training Fellowship (MOH-001131). The SMIR is a national, ministry-funded registry run by the National Registry of Diseases Office and funded by the Ministry of Health, Singapore.

8.
Am J Cardiol ; 205: 369-378, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37639763

RESUMO

Patients with chronic kidney disease (CKD) have traditionally been excluded from randomized trials. We aimed to compare percutaneous coronary intervention versus conservative management, and early intervention (EI; within 24 hours of admission) versus delayed intervention (DI; after 24 to 72 hours of admission) in patients with non-ST-segment elevation myocardial infarction (NSTEMI) and concomitant CKD. An electronic literature search was performed to search for studies comparing invasive management to conservative management or EI versus DI in patients with NSTEMI with CKD. The primary outcome was all-cause mortality; secondary outcomes were acute kidney injury (AKI) or dialysis, major bleeding, and recurrent MI. Hazard ratios (HRs) for the primary outcome and odds ratios for secondary outcomes were pooled in random-effects meta-analyses. Eleven studies (140,544 patients) were analyzed. Invasive management was associated with lower mortality than conservative management (HR 0.62, 95% confidence interval 0.57 to 0.67, p <0.001, I2 = 47%), with consistent benefit across all CKD stages, except CKD 5. There was no significant mortality difference between EI and DI, but subgroup analyses showed significant benefit for EI in stage 1 to 2 CKD (HR 0.75, 95% confidence interval 0.58 to 0.97, p = 0.03, I2 = 0%), with no significant difference in stage 3 and 4 to 5 CKD. Invasive strategy was associated with higher odds of AKI or dialysis and major bleeding, but lower odds of recurrent MI compared with conservative management. In conclusion, in patients with NSTEMI and CKD, an invasive strategy is associated with significant mortality benefit over conservative management in most patients with CKD, but at the expense of higher risk of AKI and bleeding. EI appears to benefit those with early stages of CKD. Trial Registration: PROSPERO CRD42023405491.


Assuntos
Injúria Renal Aguda , Infarto do Miocárdio sem Supradesnível do Segmento ST , Insuficiência Renal Crônica , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio sem Supradesnível do Segmento ST/complicações , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Tratamento Conservador , Hospitalização , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia
9.
Front Cardiovasc Med ; 10: 1230894, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37564912

RESUMO

Rheumatic heart disease (RHD) remains a significant cardiovascular burden in the world even though it is no longer common in affluent countries. Centuries of history surrounding this disease provide us with a thorough understanding of its pathophysiology. Infections in the throat, skin, or mucosa are the gateway for Group A Streptococcus (GAS) to penetrate our immune system. A significant inflammatory response to the heart is caused by an immunologic cascade triggered by GAS antigen cross-reactivity. This exaggerated immune response is primarily responsible for cardiac dysfunction. Recurrent inflammatory processes damage all layers of the heart, including the endocardium, myocardium, and pericardium. A vicious immunological cycle involving inflammatory mediators, angiotensin II, and TGF-ß promotes extracellular matrix remodeling, resulting in myocardial fibrosis. Myocardial fibrosis appears to be a prevalent occurrence in patients with RHD. The presence of myocardial fibrosis, which causes left ventricular dysfunction in RHD, might be utilized to determine options for treatment and might also be used to predict the outcome of interventions in patients with RHD. This emerging concept of myocardial fibrosis needs to be explored comprehensively in order to be optimally utilized in the treatment of RHD.

10.
Nat Rev Cardiol ; 20(12): 830-844, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37474795

RESUMO

Conventional dual antiplatelet therapy (DAPT) for patients with acute coronary syndromes undergoing percutaneous coronary intervention comprises aspirin with a potent P2Y purinoceptor 12 (P2Y12) inhibitor (prasugrel or ticagrelor) for 12 months. Although this approach reduces ischaemic risk, patients are exposed to a substantial risk of bleeding. Strategies to reduce bleeding include de-escalation of DAPT intensity (downgrading from potent P2Y12 inhibitor at conventional doses to either clopidogrel or reduced-dose prasugrel) or abbreviation of DAPT duration. Either strategy requires assessment of the ischaemic and bleeding risks of each individual. De-escalation of DAPT intensity can reduce bleeding without increasing ischaemic events and can be guided by platelet function testing or genotyping. Abbreviation of DAPT duration after 1-6 months, followed by monotherapy with aspirin or a P2Y12 inhibitor, reduces bleeding without an increase in ischaemic events in patients at high bleeding risk, particularly those without high ischaemic risk. However, these two strategies have not yet been compared in a head-to-head clinical trial. In this Consensus Statement, we summarize the evidence base for these treatment approaches, provide guidance on the assessment of ischaemic and bleeding risks, and provide consensus statements from an international panel of experts to help clinicians to optimize these DAPT approaches for individual patients to improve outcomes.


Assuntos
Síndrome Coronariana Aguda , Trombose Coronária , Intervenção Coronária Percutânea , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Trombose Coronária/etiologia , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/etiologia , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Aspirina/efeitos adversos , Hemorragia/induzido quimicamente , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento
11.
Front Cardiovasc Med ; 10: 1142078, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37435049

RESUMO

Introduction: Obesity is an important risk factor for acute myocardial infarction (AMI), but the interplay between metabolic health and obesity on AMI mortality has been controversial. In this study, we aimed to elucidate the risk of short- and long-term all-cause mortality by obesity and metabolic health in AMI patients using data from a multi-ethnic national AMI registry. Methods: A total of 73,382 AMI patients from the national Singapore Myocardial Infarction Registry (SMIR) were included. These patients were classified into four groups based on the presence or absence of metabolic diseases, diabetes mellitus, hyperlipidaemia, and hypertension, and obesity: (1) metabolically-healthy-normal-weight (MHN); (2) metabolically-healthy-obese (MHO); (3) metabolically-unhealthy-normal-weight (MUN); and (4) metabolically-unhealthy-obese (MUO). Results: MHO patients had reduced unadjusted risk of all-cause in-hospital, 30-day, 1-year, 2-year, and 5-year mortality following the initial MI event. However, after adjusting for potential confounders, the protective effect from MHO on post-AMI mortality was lost. Furthermore, there was no reduced risk of recurrent MI or stroke within 1-year from onset of AMI by the MHO status. However, the risk of 1-year mortality was higher in female and Malay AMI patients with MHO compared to MHN even after adjusting for confounders. Conclusion: In AMI patients with or without metabolic diseases, the presence of obesity did not affect mortality. The exception to this finding were female and Malay MHO who had worse long-term AMI mortality outcomes when compared to MHN suggesting that the presence of obesity in female and Malay patients may confer worsened outcomes.

12.
Front Public Health ; 11: 1178054, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37342279

RESUMO

Background: The Coronavirus Disease 2019 (COVID-19) pandemic has had a significant impact on all walks of life, in particular, environmental services workers in healthcare settings had higher workload, increased stress and greater susceptibility to COVID-19 infections during the pandemic. Despite extensive literature describing the impact of the pandemic on healthcare workers such as doctors and nurses, studies on the lived experiences of environmental services workers in healthcare settings are sparse and none has been conducted in the Asian context. This qualitative study thus aimed to examine the experiences of those who worked for a year of the COVID-19 pandemic. Methods: A purposive sample of environmental services workers was recruited from a major tertiary hospital in Singapore. Semi-structured interviews were conducted in-person, lasting around 30min, and included open-ended questions pertaining to five main domains: work experiences during COVID-19, training and education needs, resource and supplies availability, communication with management and other healthcare staff, and perceived stressors and support. These domains were identified based on team discussions and literature review. The interviews were recorded and transcribed for thematic analysis, as guided by Braun and Clarke. Results: A total of 12 environmental services workers were interviewed. After the first seven interviews, no new themes emerged but an additional five interviews were done to ensure data saturation. The analysis yielded three main themes and nine subthemes, including (1) practical and health concerns, (2) coping and resilience, and (3) occupational adaptations during the pandemic. Many expressed confidence in the preventive efficacy of proper PPE, infection control practice and COVID-19 vaccination in protecting them against COVID-19 and severe illness. Having prior experience with infectious disease outbreaks and previous training in infection control and prevention appeared to be useful as well for these workers. Despite the various challenges presented by the pandemic, they could still find meaning in their everyday work by positively impacting the wellbeing of patients and other healthcare workers in the hospital. Conclusion: Besides uncovering the concerns shared by these workers, we identified helpful coping strategies, resilience factors and certain occupational adaptations, which have implications for future pandemic planning and readiness.


Assuntos
COVID-19 , Pandemias , Humanos , Centros de Atenção Terciária , Vacinas contra COVID-19 , COVID-19/epidemiologia , Ásia
13.
Asia Pac J Clin Oncol ; 19(3): 312-319, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35950298

RESUMO

INTRODUCTION: Combination therapy with immune checkpoint inhibitor (ICI) and antivascular endothelial growth factor (anti-VEGF) is currently the first line treatment for advanced hepatocellular carcinoma (aHCC). However, there are many patients who may not be able to receive combination therapy due to underlying comorbidities or resource limitations. For these patients, systemic treatment options include single agent tyrosine kinase inhibitors (TKIs) or ICI monotherapy. However, whether an optimal sequence of systemic therapy exists remains unknown. We aim to explore the impact of sequencing of TKI and ICI therapy in terms of response rates and to examine the safety of their use in sequential order. METHODS: Patients with aHCC treated with both ICI and TKI between December 30, 2013 and June 13, 2018 were retrospectively identified. Patients were classified into two groups: those who received TKI in the first-line (TKI1), followed by ICI (ICI2) and those who received ICI (ICI1) in the first-line followed by TKI (TKI2). The primary objective of the study was to identify differences in objective response rate (ORR) and disease control rate (DCR), as evaluated based on response evaluation criteria in solid tumor v1.1 for TKI1, TKI2, ICI1, and ICI2. Secondary objectives included comparison of progression free survival (PFS) for each line of therapy, overall survival (OS) and adverse events (AEs). RESULTS: Twenty-seven and 23 patients were classified into group 1 and 2, respectively. Objective response rates of TKI1 and TKI2 were 3.8% and 17.6%, respectively (p = .28); DCR to TKI1 versus TKI2 was 23.1% versus 35.3% (p = .49). ORRs of ICI1 and ICI2 were 8.7% and 14.3%, respectively (p = .66); DCR to ICI2 versus ICI1 was 56.5% versus 42.9% (p = .37). Median PFS was not significant between TKI1 and TKI2 (PFS 3.06 versus 1.61 months, p = .097) as well as between ICI2 and ICI1 (PFS 1.84 versus 2.37 month, p = .32). Median OS was also not significantly different between both groups (OS 20.63 versus 13.93 months, p = .20) on univariable and multivariable analysis (OS adjusted hazard ratio [HR] 2.07, 95% CI .83-5.18, p = .118). The proportion of patients who experienced adverse events of any grade was similar in both groups (TKI1 59.3% versus TKI2 52.2%; ICI1 78.3% versus ICI2 70.4%). CONCLUSION: Our study suggests that the sequence of TKI versus ICI therapy in patients with aHCC may not matter, given similar efficacy and toxicity profile when either agent is received in the first or second-line setting. This finding is of value in the real-world setting, where patients may be frail or have comorbidities that render them unable to tolerate combination therapy (ICI and TKI/anti-VEGF). For these patients, sequential exposure to both classes of drugs (ICI and TKI) may be a suitable option.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Estudos Retrospectivos , Neoplasias Hepáticas/tratamento farmacológico
15.
Front Bioinform ; 2: 857577, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36304315

RESUMO

Epilepsy affects more than three million people in the United States. In approximately one-third of this population, anti-seizure medications do not control seizures. Many patients pursue surgical treatment that can include a procedure involving the implantation of electrodes for intracranial monitoring of seizure activity. For these cases, accurate mapping of the implanted electrodes on a patient's brain is crucial in planning the ultimate surgical treatment. Traditionally, electrode mapping results are presented in static figures that do not allow for dynamic interactions and visualizations. In collaboration with a clinical research team at a Level 4 Epilepsy Center, we developed N-Tools-Browser, a web-based software using WebGL and the X-Toolkit (XTK), to help clinicians interactively visualize the location and functional properties of implanted intracranial electrodes in 3D. Our software allows the user to visualize the seizure focus location accurately and simultaneously display functional characteristics (e.g., results from electrical stimulation mapping). Different visualization modes enable the analysis of multiple electrode groups or individual anatomical locations. We deployed a prototype of N-Tools-Browser for our collaborators at the New York University Grossman School of Medicine Comprehensive Epilepsy Center. Then, we evaluated its usefulness with domain experts on clinical cases.

16.
Sci Rep ; 12(1): 14270, 2022 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-35995801

RESUMO

Risk stratification plays a key role in identifying acute myocardial infarction (AMI) patients at higher risk of mortality. However, current AMI risk scores such as the Global Registry of Acute Coronary Events (GRACE) score were derived from predominantly Caucasian populations and may not be applicable to Asian populations. We previously developed an AMI risk score from the national-level Singapore Myocardial Infarction Registry (SMIR) confined to ST-segment elevation myocardial infarction (STEMI) patients and did not include non-STEMI (NSTEMI) patients. Here, we derived a modified SMIR risk score for both STEMI and NSTEMI patients and compared its performance to the GRACE 2.0 score for predicting 1-year all-cause mortality in our multi-ethnic population. The most significant predictor of 1-year all-cause mortality in our population using the GRACE 2.0 score was cardiopulmonary resuscitation on admission (adjusted hazards ratio [HR] 6.50), while the most significant predictor using the SMIR score was age 80-89 years (adjusted HR 7.78). Although the variables used in the GRACE 2.0 score and SMIR score were not exactly the same, the c-statistics for 1-year all-cause mortality were similar between the two scores (GRACE 2.0 0.841 and SMIR 0.865). In conclusion, we have shown that in a multi-ethnic Asian AMI population undergoing PCI, the SMIR score performed as well as the GRACE 2.0 score.


Assuntos
Infarto do Miocárdio , Infarto do Miocárdio sem Supradesnível do Segmento ST , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Idoso de 80 Anos ou mais , Humanos , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/efeitos adversos , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Singapura/epidemiologia
17.
Eur Cardiol ; 17: e16, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35795612

RESUMO

Obstructive sleep apnoea (OSA) is strongly associated with cardiovascular disease (CVD). However, evidence supporting this association in the Asian population is scarce. Given the differences in the epidemiology of CVD and cardiovascular risk factors, as well as differences in the availability of healthcare resources between Asian and Western countries, an Asian Pacific Society of Cardiology (APSC) working group developed consensus recommendations on the management of OSA in patients with CVD in the Asia-Pacific region. The APSC expert panel reviewed and appraised the available evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed and put to an online vote. Consensus was reached when 80% of votes for a given recommendation were in support of 'agree' or 'neutral.' The resulting statements provide guidance on the assessment and treatment of OSA in patients with CVD in the Asia-Pacific region. The APSC hopes for these recommendations to pave the way for screening, early diagnosis and treatment of OSA in the Asia-Pacific region.

18.
J Mol Cell Cardiol ; 170: 121-123, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35764120

RESUMO

BACKGROUND: There is growing recognition that COVID-19 does cause cardiac sequelae. The underlying mechanisms involved are still poorly understood to date. Viral infections, including COVID-19, have been hypothesized to contribute to autoimmunity, by exposing previously hidden cryptic epitopes on damaged cells to an activated immune system. Given the high incidence of cardiac involvement seen in COVID-19, our aim was to determine the frequency of anti-DSG2 antibodies in a population of post COVID-19 patients. METHODS AND RESULTS: 300 convalescent serum samples were obtained from a group of post COVID-19 infected patients from October 2020 to February 2021. 154 samples were drawn 6 months post-COVID-19 infection and 146 samples were drawn 9 months post COVID infection. 17 samples were obtained from the same patient at the 6- and 9- month mark. An electrochemiluminescent-based immunoassay utilizing the extracellular domain of DSG2 for antibody capture was used. The mean signal intensity of anti-DSG2 antibodies in the post COVID-19 samples was significantly higher than that of a healthy control population (19 ± 83.2 in the post-COVID-19 sample vs. 2.1 ± 7.2 (p < 0. 0001) in the negative control healthy population). Of note, 29.3% of the post COVID-19 infection samples demonstrated a signal higher than the 90th percentile of the control population and 8.7% were higher than the median found in ARVC patients. The signal intensity between the 6-month and 9-month samples did not differ significantly. CONCLUSIONS: We report for the first time that recovered COVID-19 patients demonstrate significantly higher and sustained levels of anti-DSG2 autoantibodies as compared to a healthy control population, comparable to that of a diagnosed ARVC group.


Assuntos
COVID-19 , Autoanticorpos/imunologia , COVID-19/sangue , COVID-19/complicações , COVID-19/imunologia , Desmogleína 2/imunologia , Humanos , Síndrome de COVID-19 Pós-Aguda
19.
Immunology ; 167(2): 263-274, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35751563

RESUMO

To determine the antibody responses elicited by different vaccines against SARS-CoV-2, we compared antibody responses in individuals 3 months post-vaccination in those who had received different vaccines in Sri Lanka. Abs to the receptor binding domain (RBD) of the ancestral (wild type) virus (WT) as well as to variants of concern (VoCs), and ACE2 blocking Abs, were assessed in individuals vaccinated with Moderna (n = 225), Sputnik V (n = 128) or Sputnik light (n = 184) and the results were compared with previously reported data on Sinopharm and AZD1222 vaccinees. A total of 99.5% of Moderna, >94% of AZD1222 or Sputnik V and >70% of Sputnik light, >60% of Sinopharm vaccine recipients, had a positive response to ACE2 blocking antibodies. The ACE2 blocking antibody levels were highest to lowest was Moderna > Sputnik V/AZD1222 (had equal levels) > Sputnik light > Sinopharm. All Moderna recipients had antibodies to the RBD of WT, alpha and beta, while positivity rates for delta variant was 80%. The positivity rates for Sputnik V vaccinees for the WT and VoCs were higher than for AZD1222 vaccinees while those who received Sinopharm had the lowest positivity rates (<16.7%). The total antibodies to the RBD were highest for the Sputnik V and AZD1222 vaccinees. The Moderna vaccine elicited the highest ACE2 blocking antibody levels followed by Sputnik V/AZD1222, while those who received Sinopharm had the lowest levels. These findings highlight the need for further studies to understand the effects on clinical outcomes.


Assuntos
COVID-19 , Vacinas , Enzima de Conversão de Angiotensina 2 , Anticorpos Bloqueadores , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , ChAdOx1 nCoV-19 , Humanos , SARS-CoV-2 , Sri Lanka
20.
Front Cardiovasc Med ; 9: 876465, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35497977

RESUMO

Background: Acute myocardial infarction (AMI) cases have decreased in part due to the advent of targeted therapies for standard modifiable cardiovascular disease risk factors (SMuRF). Recent studies have reported that ST-elevation myocardial infarction (STEMI) patients without SMuRF (termed "SMuRF-less") may be increasing in prevalence and have worse outcomes than "SMuRF-positive" patients. As these studies have been limited to STEMI and comprised mainly Caucasian cohorts, we investigated the changes in the prevalence and mortality of both SMuRF-less STEMI and non-STEMI (NSTEMI) patients in a multiethnic Asian population. Methods: We evaluated 23,922 STEMI and 62,631 NSTEMI patients from a national multiethnic registry. Short-term cardiovascular and all-cause mortalities in SMuRF-less patients were compared to SMuRF-positive patients. Results: The proportions of SMuRF-less STEMI but not of NSTEMI have increased over the years. In hospitals, all-cause and cardiovascular mortality and 1-year cardiovascular mortality were significantly higher in SMuRF-less STEMI after adjustment for age, creatinine, and hemoglobin. However, this difference did not remain after adjusting for anterior infarction, cardiopulmonary resuscitation (CPR), and Killip class. There were no differences in mortality in SMuRF-less NSTEMI. In contrast to Chinese and Malay patients, SMuRF-less patients of South Asian descent had a two-fold higher risk of in-hospital all-cause mortality even after adjusting for features of increased disease severity. Conclusion: SMuRF-less patients had an increased risk of mortality with STEMI, suggesting that there may be unidentified nonstandard risk factors predisposing SMuRF-less patients to a worse prognosis. This group of patients may benefit from more intensive secondary prevention strategies to improve clinical outcomes.

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