Combined transepicardial and transseptal implantation of autologous CD 133+ bone marrow cells during bypass grafting improves cardiac function in patients with low ejection fraction.

OBJECTIVES: Autologous CD133+ bone marrow stem cells may improve cardiac function. This randomized, single-blind clinical trial inquired whether a combined transepicardial and transseptal implantation of CD133+ stem cells during coronary artery bypass grafting (CABG) improve cardiac function with ejection fraction (EF) changes as a primary endpoint in patients with low EF. METHODS: Thirty patients with coronary heart disease and EF <35% were randomized to undergo CABG alone or CABG with transseptal and transepicardial implantation of CD133+. Cardiac function was evaluated using cardiac magnetic resonance imaging (MRI) before and 6 months after CABG. RESULTS: Preoperative EF was lower in the intervention group (25.88% ± 5.66%) than in the control group (30.18% ± 3.85%; P = .04). The adverse event incidence was similar between both groups. At 6 months, EF changes were significantly higher (8.69% ± 9.49; P = .04) in the CD133+ group than in the CABG-only group. Compared to the control group, significant improvements were seen in the wall motion score index (P = .003) and scar size proportion (P = .047) in the CD133+ group. The quality of life (QOL), assessed by a 6-minute walking test, showed considerable improvement in the CD133+ group compared to that in the control group (P = .03). The Minnesota Living with Heart Failure Questionnaire (MLHFQ) scale did not show improvement in the intervention group (P = .09, vs control). CONCLUSION: Combined transepicardial and transseptal autologous CD133+ BMC implantation during bypass grafting improved cardiac function in low EF coronary artery disease patients.

Correlation P2Y12 Genetic Polymorphism As Risk Factor of Clopidogrel Resistance in Indonesian Stroke Patients.

Background: Stroke is one of the highest causes of disability and mortality in several countries worldwide. Secondary prevention is important in the management of stroke. Clopidogrel is widely used in Asia as secondary prevention for ischemic stroke, even though several studies in Western show limited data related to clopidogrel resistance in Asia. This study aims to determine the correlation between P2Y12 genetic polymorphism and clopidogrel resistance in Indonesia. Methods: This study was conducted on one-year duration, the subjects were chosen through the consecutive sampling method, all subjects were examined for genetics and resistance to clopidogrel. The data were analyzed through statistical analysis, a bivariate analysis was conducted to determine the correlation between several variables and the resistance variable. This study employed resistance diagnostic methods with VerifyNow. Polymorphism of receptor P2Y12 was tested with the Polymerase Chain Reaction method (PCR) and analysis of restriction fragment length polymorphism (RFLP). The genes tested in this study were G52T and C34T. Results: The number of participants in this study was 112. Examination of gene P2Y12 showed that the majority was homozygote, wild-type C34T allele (67%), and G52T (66.1%). There was no significant correlation between clopidogrel resistance and gene G52T and C34T of P2Y12 (p > 0.05). Hb levels significantly correlated with P2Y12 G52T (p = 0.024). Meanwhile, Fatty Liver significantly correlated with P2Y12 C34T (p = 0.037). Conclusion: Indonesia showed a low clopidogrel resistance rate and a very low C34T and G52T allele P2Y12 gene mutation, meaning that Indonesia had low mutations in the P2Y12. This is the cause of clopidogrel resistance in this study only 15%. Therefore, in a region with less clopidogrel resistance, examination of the P2Y12 gene would not give significant results.

The role of clopidogrel resistance-related genetic and epigenetic factors in major adverse cardiovascular events among patients with acute coronary syndrome after percutaneous coronary intervention.

Despite patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) and receiving clopidogrel therapy, some patients still experience major adverse cardiovascular events (MACEs). Clopidogrel resistance, which may be regulated by genetic and epigenetic factors, may play a role in MACEs. This study aimed to determine the association between genetic (CYP2C19 and P2Y12 polymorphisms) and epigenetic (DNA methylation of CYP2C19 and P2Y12 and miRNA-26a expression) factors and their effects on MACEs among post-PCI patients. Post-PCI patients who received a standard dosage of clopidogrel at Harapan Kita Hospital between September 2018 and June 2020 were included in this study. MACEs were observed in patients within 1 year after PCI. Platelet aggregation was assessed using light transmission aggregometry (LTA). DNA methylation of CYP2C19 and P2Y12 was assessed using the bisulfite conversion method. CYP2C19 and P2Y12 polymorphisms and miRNA-26a expression were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). Among a total of 201 subjects, 49.8% were clopidogrel-resistant, and 14.9% experienced MACEs within 1 year after PCI (death was 7.5%). Hypomethylation of CYP2C19 (p = 0.037) and miRNA-26a upregulation (p = 0.020) were associated with clopidogrel resistance. CYP2C19*2/*3 polymorphisms (p = 0.047) were associated with MACEs in 1 year. This study demonstrated that hypomethylation of CYP2C19 and miRNA-26a upregulation increased the risk of clopidogrel resistance in post-PCI patients, but there was no correlation between clopidogrel resistance and MACEs. However, CYP2C19*2/*3 polymorphisms were the factors that predicted MACEs within 1 year.

Enteric disease surveillance under the AFHSC-GEIS: current efforts, landscape analysis and vision forward.

The mission of the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) is to support global public health and to counter infectious disease threats to the United States Armed Forces, including newly identified agents or those increasing in incidence. Enteric diseases are a growing threat to U.S. forces, which must be ready to deploy to austere environments where the risk of exposure to enteropathogens may be significant and where routine prevention efforts may be impractical. In this report, the authors review the recent activities of AFHSC-GEIS partner laboratories in regards to enteric disease surveillance, prevention and response. Each partner identified recent accomplishments, including support for regional networks. AFHSC/GEIS partners also completed a Strengths, Weaknesses, Opportunities and Threats (SWOT) survey as part of a landscape analysis of global enteric surveillance efforts. The current strengths of this network include excellent laboratory infrastructure, equipment and personnel that provide the opportunity for high-quality epidemiological studies and test platforms for point-of-care diagnostics. Weaknesses include inconsistent guidance and a splintered reporting system that hampers the comparison of data across regions or longitudinally. The newly chartered Enterics Surveillance Steering Committee (ESSC) is intended to provide clear mission guidance, a structured project review process, and central data management and analysis in support of rationally directed enteric disease surveillance efforts.

Effect of PCSK9 E670G and R46L Polymorphisms on Major Adverse Cardio-Cerebrovascular Events in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

Major adverse cardio-cerebrovascular events (MACCE) in ST-segment elevation myocardial infarction (STEMI) are still high, although there have been advances in pharmacology and interventional procedures. Proprotein convertase subtilisin/Kexin type 9 ( PCSK9 ) is a serine protease regulating lipid metabolism associated with inflammation in acute coronary syndrome. The MACCE is possibly related to polymorphisms in PCSK9 . A prospective cohort observational study was designed to confirm the association between polymorphism of E670G and R46L in the PCSK9 gene with MACCE in STEMI. The Cox proportional hazards model and Spearman correlation were utilized in the study. The Genotyping of PCSK9 and ELISA was assayed. Sixty-five of 423 STEMI patients experienced MACCE in 6 months. The E670G polymorphism in PCSK9 was associated with MACCE (hazard ratio = 45.40; 95% confidence interval: 5.30-390.30; p = 0.00). There was a significant difference of PCSK9 plasma levels in patients with previous statin consumption (310 [220-1,220] pg/mL) versus those free of any statins (280 [190-1,520] pg/mL) ( p = 0.001). E670G polymorphism of PCSK9 was associated with MACCE in STEMI within a 6-month follow-up. The plasma PCSK9 level was higher in statin users.

Increase in the risk of clopidogrel resistance and consequent TIMI flow impairment by DNA hypomethylation of CYP2C19 gene in STEMI patients undergoing primary percutaneous coronary intervention (PPCI).

Clopidogrel resistance is an important risk factor of ischemic event recurrence after optimal antiplatelet therapy. This study aims to investigate the role of CYP2C19 gene DNA methylation as one of the epigenetic factors for the risk of clopidogrel resistance in STEMI patients undergoing PPCI. ST-segment elevation myocardial infarction (STEMI) patients undergoing PPCI were pretreated with clopidogrel, and their platelet function was measured using VerifyNow™ assay. The criteria for high on-treatment platelet reactivity (HPR) were defined according to the expert consensus criteria (PRU >208). DNA methylation of the CYP2C19 gene was performed using bisulfite genomic sequencing technology. Furthermore, clinical, laboratory, and angiographic data including TIMI flow were collected. Among 122 patients, clopidogrel resistance was found in 22%. DNA methylation level percentage was lower in the clopidogrel resistance group (76.7 vs. 88.8, p-value .038). But, the <50% methylation group was associated with increased risk of clopidogrel resistance (OR =4.5, 95%CI =2.1-9.3, p-value = .018). This group was also found to have suboptimal post-PCI TIMI flow (OR =3.4 95%CI =1.3-8.7, p-value =.045). The lower DNA methylation level of the CYP2C19 gene increases the risk of clopidogrel resistance and subsequent poorer clinical outcome.

Intronic Variant of MUTYH Gene Exhibits A Strong Association with Early Onset of Breast Cancer Susceptibility in Indonesian Women Population.

OBJECTIVE: Several studies have recently indicated a huge shifting pattern toward early age onset cases in breast cancer (BC) patients. However, the studies exerted relatively limited to the Caucasian population. This preliminary study is aimed to investigate the genetic risk factors for young BC patients specifically in Indonesia population. METHODS: DNA samples were extracted from 79 BC patients aged younger than 40 years old and 90 healthy samples. These DNA samples were sequenced using Illumina NextSeq 500 platform and preprocessed to extract the single-nucleotide polymorphisms (SNPs) data. Firstly, multiple univariate logistic regressions were performed to test the association between each SNP and BC incidence in young patients. Furthermore, to analyze the polygenic effects derived from multiple SNPs, we employed a multivariate logistics regression. RESULTS: There were only 15 SNPs passed our 95% call rate threshold thus subsequently were used in the association test. One of these variants, rs3219493, emerged to be significantly associated with early-onset BC (p-value = 0.025, OR = 3.750, 95% CI = 1.178-11.938). This result is consistent with the multivariate logistic regression model, where the pertinent variant was found statistically significant (p-value = 0.008, OR = 8.398, 95% CI = 1.720-40.920). This variant was identified as an intronic variant within MUTYH gene which has been reported in several published studies to exhibit an association with the incidence of breast cancer in China, Italy and Sephardi Jews population. However, there is no evident this gene impacting the risk of developing early onset of BC in Indonesia population. CONCLUSION: Despite our limitation in terms of sample size analyzed in this preliminary study, our finding on significant association of intronic MUTHY with the early onset of BC in Indonesia led to a broadened insight of population-based unique aspect to being taken into an in-depth account for and advancement of chemotherapy.

Influenza virus infection among pediatric patients reporting diarrhea and influenza-like illness.

BACKGROUND: Influenza is a major cause of morbidity and hospitalization among children. While less often reported in adults, gastrointestinal symptoms have been associated with influenza in children, including abdominal pain, nausea, vomiting, and diarrhea. METHODS: From September 2005 and April 2008, pediatric patients in Indonesia presenting with concurrent diarrhea and influenza-like illness were enrolled in a study to determine the frequency of influenza virus infection in young patients presenting with symptoms less commonly associated with an upper respiratory tract infection (URTI). Stool specimens and upper respiratory swabs were assayed for the presence of influenza virus. RESULTS: Seasonal influenza A or influenza B viral RNA was detected in 85 (11.6%) upper respiratory specimens and 21 (2.9%) of stool specimens. Viable influenza B virus was isolated from the stool specimen of one case. During the time of this study, human infections with highly pathogenic avian influenza A (H5N1) virus were common in the survey area. However, among 733 enrolled subjects, none had evidence of H5N1 virus infection. CONCLUSIONS: The detection of influenza viral RNA and viable influenza virus from stool suggests that influenza virus may be localized in the gastrointestinal tract of children, may be associated with pediatric diarrhea and may serve as a potential mode of transmission during seasonal and epidemic influenza outbreaks.

Group A rotavirus-associated diarrhea in children seeking treatment in Indonesia.

BACKGROUND: Globally, group A rotavirus causes significant morbidity and mortality among children. Limited data exist on the epidemiology of rotavirus disease among Indonesian children. OBJECTIVES: We describe the epidemiology of rotavirus-associated diarrhea among Indonesian children <6 years of age, including clinical symptoms and genotypes. STUDY DESIGN: We conducted a hospital-based, case series study at four referral hospitals between February 2004 and February 2005 among children with diarrhea. Rotavirus positivity was defined by a positive result from either EIA or RT-PCR. A semi-nested RT-PCR was used to determine specific rotavirus genotypes. RESULTS: 1660 stools were tested for pathogens. The overall rotavirus prevalence was 45.5%. Children with rotavirus-associated diarrhea were significantly younger (p<0.0001) and more likely to be hospitalized (81.3% versus 72.2%; p<0.0001). Symptoms associated with rotavirus included, vomiting, fever, nausea, fatigue and dehydration, while bloody stool was significantly less common with rotavirus-associated diarrhea. CONCLUSION: Rotavirus was an important contributor of morbidity to our study sample. Rotavirus genotyping demonstrated a temporal shift from G1-G4 to G9, but this was highly associated with the P[8] gene, suggesting that a multivalent rotavirus vaccine, incorporating G9 P[8] antigen, may reduce the burden of diarrheal illnesses among Indonesian children.

Early detection of dengue infections using cluster sampling around index cases.

A two-year study using a cluster investigation method was conducted in West Jakarta, Indonesia to demonstrate the detection of dengue cases prior to onset of clinical illness. The clusters consisted of family members and neighbors of 53 hospitalized dengue index cases. Among 785 adult and child volunteers enrolled, 17 (2.2%) post-enrollment dengue (PED) infections were identified. Eight PED cases were asymptomatic and nine were symptomatic. Symptomatic cases included eight with dengue fever and one with dengue hemorrhagic fever (DHF) (grade II). Among the eight asymptomatic PED cases, viremia was detected in two. Eleven volunteers had acute dengue infections at the time of enrollment. Four of the 11 developed DHF, resulting in a total of five DHF cases detected during the investigation. This study design can serve as a benchmark for future investigations that seek to define early immunologic events following dengue infections that contribute to the development of DHF.

Epidemiology of dengue and dengue hemorrhagic fever in a cohort of adults living in Bandung, West Java, Indonesia.

A prospective study of dengue fever (DF) and dengue hemorrhagic fever (DHF) was conducted in a cohort of adult volunteers from two textile factories located in West Java, Indonesia. Volunteers in the cohort were bled every three months and were actively followed for the occurrence of dengue (DEN) disease. The first two years of the study showed an incidence of symptomatic DEN disease of 18 cases per 1,000 person-years and an estimated asymptomatic/ mild infection rate of 56 cases per 1,000 person-years in areas of high disease transmission. In areas where no symptomatic cases were detected, the incidence of asymptomatic or mild infection was 8 cases per 1,000 person-years. Dengue-2 virus was the predominant serotype identified, but all four serotypes were detected among the cohort. Four cases of DHF and one case of dengue shock syndrome (DSS) were identified. Three of the four DHF cases were due to DEN-3 virus. The one DSS case occurred in the setting of a prior DEN-2 virus infection, followed by a secondary infection with DEN-1 virus. To our knowledge, this is the first report of a longitudinal cohort study of naturally acquired DF and DHF in adults.

Influenza surveillance in Indonesia: 1999-2003.

Although influenza is recognized for its worldwide importance, little is known about the disease from tropical countries like Indonesia. From August 1999 through January 2003, a surveillance study was conducted in clinics at 6 sentinel locations. Adults (age, >14 years) and children (age, 4-14 years) presenting with respiratory symptoms suggestive of influenza were asked to enroll in the study. Nasal and pharyngeal swabs were examined by virus isolation, polymerase chain reaction, and rapid immunochromatographic tests. A total of 3079 specimens were collected from 1544 participants. Influenza infection was confirmed in 172 volunteers (11.1%) presenting with influenza-like illness. Influenza A (H1N1 and H3N2) and B viruses were detected at all sites. Peak prevalence tended to coincide with the respective rainy seasons, regardless of location. In light of the recent epidemic of severe acute respiratory syndrome, continued influenza surveillance would be useful in strengthening the infrastructure of the Indonesian public health system.

A serological study of Chikungunya virus transmission in Yogyakarta, Indonesia: evidence for the first outbreak since 1982.

A study of epidemic transmission of Chikungunya virus (CHIK) was initiated in April 1999 in Yogyakarta, Indonesia. Three hundred seventeen volunteers from three kelurahans (sub-districts) were recruited. Anti-CHIK IgG antibodies were detected in 68% to 74% of cases and 28% to 32% of controls. In the kelurahan with no reported CHIK illness, 29% of cases and 28% of controls had anti-CHIK IgG antibodies. None of these cases demonstrated anti-CHIK IgM antibodies. In the two kelurahans with disease activity, anti-CHIK IgM antibodies were detected in 3% to 36% of cases, with the highest percentage from the kelurahan with recently reported cases. Ten percent of controls from Gowok had anti-CHIK IgM detected in their serum. Twelve acutely ill volunteers were later included from the kelurahan Pilahan for virus identification. Samples from two volunteers were culture- and RT-PCR-positive for CHIK. This is the first documentation of epidemic transmission of CHIK in Indonesia since 1982.

A serological study of Chikungunya virus transmission in Yogyakarta, Indonesia: evidence for the first outbreak since 1982.

A study of epidemic transmission of Chikungunya virus (CHIK) was initiated in April 1999 in Yogyakarta, Indonesia. Three hundred seventeen volunteers from three kelurahans (sub-districts) were recruited. Anti-CHIK IgG antibodies were detected in 68% to 74% of cases and 28% to 32% of controls. In the kelurahan with no reported CHIK illness, 29% of cases and 28% of controls had anti-CHIK IgG antibodies. None of these cases demonstrated anti-CHIK IgM antibodies. In the two kelurahans with disease activity, anti-CHIK IgM antibodies were detected in 3% to 36% of cases, with the highest percentage from the kelurahan with recently reported cases. Ten percent of controls from Gowok had anti-CHIK IgM detected in their serum. Twelve acutely ill volunteers were later included from the kelurahan Pilahan for virus identification. Samples from two volunteers were culture- and RT-PCR-positive for CHIK. This is the first documentation of epidemic transmission of CHIK in Indonesia since 1982.