Clustered regularly interspaced palindromic repeats-cas9-based strategies towards HIV eradication: A literature review.

OBJECTIVE: Despite Human Immunodeficiency Virus (HIV) being a major global health burden, no currently available therapy can eliminate it. One of the major challenges in developing treatment is the presence of latent HIV reservoirs. On the other hand, development of Clustered Regularly Interspaced Palindromic Repeats-Cas9 (CRISPR-Cas9) has made genome editing possible and thus can be used to address HIV latency and successfully treat HIV. This literature review aims to identify and appraise existing CRISPR-Cas9 strategies that address HIV treatment, particularly during latency. METHODS: The PubMed Database was used to retrieve relevant articles. This review included articles that mentioned the use of CRISPR-Cas9 as a treatment for HIV and are written in English and/or Indonesian language. RESULTS: The included studies (n = 17) showed that the CRISPR-Cas9 system can be utilized to disrupt the HIV-1 genome to inhibit viral reproduction and virulence. This system can be further optimized by combining several CRISPR-Cas9 systems. However, the use of CRISPR-Cas9 may cause HIV resistance, particularly to its guide RNA. This technique has also never been applied in vivo, thus more research is needed before wider implementation. A limitation of this review is the lack of data regarding CRISPR-Cas9 systems quality in some studies, thus limiting appraisal. CONCLUSIONS: While the use of CRISPR-Cas9 to cure HIV seems promising, further studies regarding CRISPR-Cas9 quality, potential for development of gRNA-resistant HIV-1 strains and in vivo demonstration of the techniques are needed to progress this concept toward HIV eradication.

Delayed menarche in children and adolescents with type 1 diabetes mellitus: a systematic review and meta-analysis.

Several studies have reported an association between age at menarche and the onset of type-1 diabetes mellitus (T1DM). This review compared the age at menarche in patients who had menarche after T1DM diagnosis with that of patients who were healthy and/or had menarche before T1DM diagnosis. Searches were conducted using four databases. The outcome was the age at menarche of patients who had menarche after T1DM diagnosis and patients who were healthy and/or had menarche before T1DM diagnosis. A qualitative analysis was performed using the JBI (Joanna Briggs Institute) Critical Appraisal. Quantitative analysis of the mean differences was performed using Revman 5.4 tool. A total of 1952 studies were obtained from the initial search. The final results were 13 articles that met the inclusion criteria for the qualitative assessment and eight for the quantitative assessment. Eight studies included 1030 patients who had menarche after being diagnosed with T1DM and 1282 patients who were healthy and/or had menarche before T1DM diagnosis. The meta-analysis showed a cumulative effect on a mean difference of 0.87 (95% CI: 0.75; 0.99, p-value < 0.00001), indicating a later age at menarche in patients who had menarche after T1DM diagnosis. The age at menarche was later in patients who had menarche after T1DM diagnosis compared to healthy subjects and those who had menarche beforehand.

Immunogenicity and Safety of Half-Dose Heterologous mRNA-1273 Booster Vaccination for Adults Primed with the CoronaVac® and ChAdOx1-S Vaccines for SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) has been extensively researched, particularly with regard to COVID-19 vaccines. However, issues with logistics and availability might cause delays in vaccination programs. Thus, the efficacy and safety of half-dose heterologous mRNA should be explored. This was an open-label observational study to evaluate the immunogenicity and safety of half-dose mRNA-1273 as a booster vaccine among adults aged >18 years who underwent a complete primary SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination regimen with CoronaVac® and ChAdOx1-S. Adverse events (AEs), seropositivity rate, seroconversion, geometric mean titer (GMT) of SARS-CoV-2 antibodies, neutralizing antibodies, and T cells (CD4+ and CD8+) specific for SARS-CoV-2 were analyzed. Two hundred subjects were included in the final analysis, with 100 subjects in each priming vaccine group. Most of the AEs were mild, with systemic manifestations occurring between 1 and 7 days following vaccination. A significant difference was observed in the GMT and seropositivity rate following booster dose administration between the two groups. CD8+/CD3+, IFN (interferon)-producing CD8+, and TNF (tumor necrosis factor)-producing CD8+ cells showed significant increases in both groups. The administration of the half-dose mRNA-1273 booster is safe and effective in increasing protection against SARS-CoV-2 infection.

Factors Associated with All-Cause 30-Day Mortality in Indonesian Inpatient COVID-19 Patients at Cipto Mangunkusumo National General Hospital.

Introduction: Indonesia, as a developing country, has limited data on the factors associated with 30-day mortality in COVID-19 patients in Indonesia. As a matter of fact, study analyzing factors associated with 30-day mortality of COVID-19 infection in Indonesia has never been conducted. This study aims to fill this gap in the literature by conducting a large-scale analysis of factors associated with 30-day mortality in COVID-19 patients in Indonesia. Method: This study employed a single-center retrospective cohort observational design, and was conducted at Cipto Mangunkusumo National General Hospital between the years 2022 and 2023. Sampling was conducted using the consecutive sampling method. The study included patients aged 18 years and above who had been confirmed to have COVID-19 infection. Survival analysis was conducted using Kaplan-Meier and multivariate Cox regression analysis. Result: Our study included a total of 644 patients, with 120 patients (18.6%) expiring within 30 days. In the multivariate analysis using the backward Wald method, severe COVID-19 (HR: 7.024; 95% CI: 3.971-12.744; p value: <0.0001), moderate COVID-19 infection (HR: 1.660; 95% CI: 1.048-2.629; p value: 0.031), liver cirrhosis (HR: 3.422; 95% CI: 1.208-9.691; p value: 0.021), female sex (HR: 1.738; 95% CI: 1.187-2.545; p value: 0.004), old age (HR: 2.139; 95% CI: 1.279-3.577; p value: 0.004), high leukocyte (HR: 11.502; 95% CI: 1.523-86.874; p value: 0.018), high NLR (HR: 1.720; 95% CI: 1.049-2.819; p value: 0.032), high CRP (HR: 1.906; 95% CI: 1.092-3.329; p value: 0.023), high procalcitonin (HR: 3.281; 95% CI: 1.780-6.049; p value: 0.001), and high creatinine (HR: 1.863; 95% CI: 1.240-2.800; p value: 0.003) were associated with 30-day mortality from COVID-19 infection. Subgroup analysis excluding cancer patients showed that age, D-Dimer, CRP, and PCT were associated with 30-day mortality in COVID-19 patients, while steroid therapy is protective. Conclusions: This study finds that COVID-19 severity, liver cirrhosis, sex, age, leukocyte, NLR, CRP, creatinine, and procalcitonin were associated with COVID-19 mortality within 30 days. These findings underscore the multifactorial nature of COVID-19 infection mortality. It is important, therefore, that patients which exhibit these factors should be treated more aggressively to prevent mortality.

Carbohydrate counting implementation on pediatric type 1 diabetes mellitus: systematic review and meta-analysis.

PURPOSE: Type 1 diabetes mellitus, which is the most common type of diabetes among children, is not curable but can be managed well without a negative effect on quality of life. One of the treatments of type 1 diabetes mellitus is carbohydrate counting. This systematic review and meta-analysis sought to evaluate the efficacy of carbohydrate counting with regard to hemoglobin A1c (HbA1c) reduction in children with type 1 diabetes mellitus. METHODS: Nine studies were assessed, with the primary outcome being glycemic control (HbA1c changes). We searched the following electronic databases: ProQuest, PubMed, Scopus, and ScienceDirect. The quality of studies included was assessed using the risk of bias for randomized control trials and the JBI Critical Appraisal Checklist for observational and cross-sectional studies. Quantitative analyses were made and extrapolated into a forest plot. RESULTS: A total of 1,693 articles were identified. Four reviewers independently screened titles and abstracts. Of the 36 articles screened, 34 articles were found to be eligible. Of these, 25 studies were excluded because of unsuitable outcomes and study designs. Nine articles were included in the final analysis. Meta-analysis showed that there was a reduction in HbA1c in the carbohydrate counting group as compared to the control group. The cumulative effect of carbohydrate counting on HbA1c was a mean difference of -0.55 (95% confidence interval, -0.81 to -0.28, P<0.001). All of the studies exhibited similar results with the mean difference reduction favoring the interventional group. However, the heterogeneity analysis revealed an I2 value of 88%, implying high heterogeneity in the meta-analysis. CONCLUSION: The meta-analysis showed evidence favoring the use of carbohydrate counting in the management of type 1 diabetes mellitus.

Exploring the Potential of Poguntano Extract on Diabetes Management: Systematic Review and Meta-Analysis.

Background: Poguntano (Picria fel-terrae Merr) is a traditional herb commonly used as a blood glucose lowering agent in Indonesia. However, the effectiveness of the herb has not yet been established. Objective: This systematic review and meta-analysis aim to review the hypoglycemic effect of Poguntano extract in lowering plasma glucose levels. Methods: We conducted a literature search using peer-reviewed databases for relevant articles on Poguntano extract in animal models of diabetes. The effect size was pooled using a random effect model. Results: Two animal studies were included in the systematic review and meta-analysis. There was a significant difference in plasma glucose levels between diabetic control and rats treated with Puguntano extract (MD: 28.77; 95%CI: 6.20-51.34; p=0.01). There was no significant difference between non-diabetic control and Poguntano extract. Conclusion: Poguntano extract lowers the blood glucose levels in diabetic rats compared to control.

The Impact of Recombinant Versus Plasma-Derived Factor VIII Concentrates on Inhibitor Development in Previously Untreated Patients With Hemophilia A: A 2021 Update of a Systematic Review and Meta-Analysis.

Hemophilia A, the most common hereditary disorder, is caused by clotting factor deficiency. Challenges encountered in the current treatment of hemophilia A [factor VIII (FVIII) replacement therapy] due to inhibitor development have caused ineffective treatment as well as morbidity and mortality among patients. However, there are no studies comparing the two types of FVIII treatments in terms of inhibitor development rate. Therefore, we conducted this systematic review to devise a better treatment option with a lower risk of inhibitor development. The systematic review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and by searching several databases. Data extraction on study characteristics and outcomes was conducted. Reviewers also conducted a risk of bias assessment on all studies. All eligible studies for quantitative analysis were then processed using RevMan 5.4.1 and the data was extrapolated into cumulative outcomes and expressed in forest and funnel plots. Nine studies were included in the meta-analysis, involving a total of 2,531 hemophilia A patients who were followed up from birth until death. A higher incidence of inhibitor development was found to be associated with recombinant FVIII (rFVIII) [odds ratio (OR)=1.57, 95% confidence interval (CI): 0.95-2.59; hazard ratio (HR)=1.89, 95% CI: 1.15-3.12]. The same trend was also found for high-responding inhibitors (OR=1.38, 95% CI: 0.70-2.70; HR=1.42, 95% CI: 0.84-2.39). rFVIII is associated with a higher risk of overall and high-responding inhibitor development compared to plasma-derived FVIII (pdFVIII).

Efficacy and Safety of Insulin Degludec/Insulin Aspart (IDegAsp) in Type 2 Diabetes: Systematic Review and Meta-Analysis.

Type 2 diabetes mellitus is a prevalent metabolic disease requiring tight glycemic control of basal and postprandial glucose levels. Treatment intensification using separate basal and bolus injections increased the number of injections and reduced cost-effectivity, leading to decreased compliance and failure of glycemic control. Insulin Degludec/Insulin Aspart (IDegAsp), a novel premix of basal and bolus insulin, is one of the potential treatments for reducing the number of injections. However, its efficacy and safety have not been reviewed clearly. Therefore, this systematic review aims to compare the efficacy and safety of IDegAsp with standard basal and basal plus bolus insulin regimens. A systematic review of four databases (Pubmed, Scopus, Science Direct, and Proquest) was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Search results were screened by eligibility criteria and critically appraised by the Oxford Centre for Evidence-Based Medicine (CEBM) tool and the Cochrane risk-of-bias assessment tool. Meta-Analysis was done using Review Manager to obtain cumulative outcomes from hemoglobin A1C (HbA1C) changes, hypoglycemia incidents, and weight gain from all studies. Out of 132 search results, 10 studies were reviewed. IDegAsp once-daily administration was proven beneficial in reducing HbA1c levels and nocturnal hypoglycemia incidences, while IDegAsp twice-daily administration was proven beneficial in lowering hypoglycemia incidence and nocturnal hypoglycemia incidence. IDegAsp yielded better glycemic index results and lowered hypoglycemic incidents in the meta-analysis. Thus, it is concluded that IDegAsp once daily with stepwise titration on the largest meal of the day achieved most benefits with minimal risks.

Role of Anti-B-Cell Maturation Antigen (BCMA) in the Management of Multiple Myeloma.

Over the past few decades, treatment options have become more advanced for multiple myeloma (MM), one of the most prevalent hematological cancers; however, multiple myeloma remains an incurable disease due to its poor response to therapy and high rates of resistance, which cause relapsed/refractory or multiple myeloma. Researchers have described anti-BCMA (B-cell maturation antigen) as a promising treatment regimen that targets the BCMA biomarker in the affected plasma cells. BCMA is a protein that is specifically expressed in plasma-cell neoplasms by using several mechanisms, such as CAR T cells (Chimeric Antigen Receptor T cells), antibody-drug conjugates, and bispecific T-cell engagers, thus allowing for a rapid response in the treatment of resistant or relapsed/refractory multiple myeloma patients. Anti-BCMA treatment is novel and specific in its mechanisms of action, with noninferior complete responses, higher overall survival rates, and fewer reported adverse events compared to other currently available treatment of MM. In this review, we compared anti-BCMA mechanisms with those of previously available therapies, such as those using immunomodulators and proteasome inhibitors, and discussed the advantages of using anti-BCMA as a potential first-line treatment for multiple myeloma patients.

The potential of volatile organic compounds-based breath analysis for COVID-19 screening: a systematic review & meta-analysis.

COVID-19 is a major problem with an increasing incidence and mortality. The discovery of Volatile Organic Compounds (VOCs) based on breath analysis offers a reliable, rapid, and affordable screening method. This study examined VOC-based breath analysis diagnostic performance for SARS-COV-2 infection compared to RT-PCR. A systematic review was conducted in 8 scientific databases based on the PRISMA guideline. Original English studies evaluating human breaths for COVID-19 screening and mentioning sensitivity and specificity value compared to RT-PCR were included. Six studies were included with a total of 4093 samples from various settings. VOCs-based breath analysis had the cumulative sensitivity of 98.2% (97.5% CI 93.1%-99.6%) and specificity of 74.3% (97.5% CI 66.4%-80.9%). Subgroup analysis on chemical analysis (GC-MS) and pattern recognition (eNose) revealed higher sensitivity in the eNose group. VOC-based breath analysis shows high sensitivity and promising specificity for COVID-19 public screening.

Efficacy and safety profile of COVID-19 mRNA vaccine in patients with hematological malignancies: Systematic review and meta-analysis.

Patient populations, including those with hematological malignancies, have different responses to COVID-19 vaccines. This study aimed to quantitatively analyze the efficacy and safety of COVID-19 mRNA vaccines in patients with hematological malignancies. Studies reporting on the efficacy and safety of COVID-19 mRNA vaccines in cohorts with hematological malignancies compared to healthy controls were systematically searched in four databases. Meta-analysis and subgroup analyses were performed to generate quantitative synthesis. Fifteen studies with 2,055 cohorts with hematological malignancies and 1,105 healthy subjects as control were included. After two doses of COVID-19 vaccination, only 60% of cohorts with hematological malignancies were seroconverted compared to healthy controls (RR 0.60; 95%CI 0.50-0.71). A single dose of the vaccine resulted in a significantly lower seroconversion rate (RR 0.30; 95%CI 0.16-0.54). Non-Hodgkin lymphoma cohorts had the lowest rate of seroconversion (RR 0.5; 95%CI 0.35-0.71) and those who received active treatments had lower immunological responses (RR 0.59; 95%CI 0.46-0.75). Antibody titers were lower in cohorts with hematological malignancies without any differences in adverse effects in both groups. In conclusion, cohorts with hematological malignancies showed a lower seroconversion rate and antibody titers after receiving COVID-19 mRNA vaccines. The type of malignancy and the status of treatment had a significant impact on the response to vaccination. The vaccines were shown to be safe for both patients with hematological malignancies and healthy controls. Booster doses and stricter health protocols might be beneficial for patient populations.

Reverse Transcriptase Loop Mediated Isothermal Amplification (RT-LAMP) for COVID-19 diagnosis: a systematic review and meta-analysis.

COVID-19 pandemic has become a global public health priority. The rapid increase in infection numbers, along with a significant number of deaths, has made the virus a serious threat to human health. Rapid, reliable, and simple diagnostic methods are critical to controlling the disease. While Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is the current diagnostic gold standard, Reverse Transcriptase Loop-Mediated Isothermal Amplification (RT-LAMP) appears to be a compelling alternative diagnostic test due to its greater simplicity, shorter time to obtain a result, and lower cost. This study examined RT-LAMP application for rapid identification of SARS-CoV-2 infection compared to the RT-PCR assay. A systematic review and meta-analysis was conducted over six scientific databases in accordance with PRISMA guidelines. Original studies published in English conducted on human clinical samples were included. Articles evaluating the sensitivity and specificity of RT-LAMP relative to RT-PCR were considered eligible. Quality assessment of bias and applicability was examined based on QUADAS-2. A total of 351 studies were found based on the keywords and search queries. Fourteen eligible case-control studies fit the mentioned criteria. Quality assessment using QUADAS-2 indicated alow risk of bias for all included studies. All case studies, containing 2,112 samples, had acumulative sensitivity of 95.5% (CI 97.5% = 90.8-97.9%) and cumulative specificity of 99.5% (CI 97.5% = 97.7-99.9%). The RT-LAMP assay could be areliable alternative COVID-19 diagnostic method due to its reduced cost and processing time compared to RT-PCR. RT-LAMP could potentially be utilized during critical high-throughput and high-demand situations.

Evaluation of Right Ventricular Outflow Tract Stenting as Palliative Treatment in Severely Cyanotic Tetralogy of Fallot: A Systematic Review and Meta-Analysis of Observational Studies.

Background: Tetralogy of Fallot (ToF) is a cardiac malformation that accounts for up to 1/10 of all congenital diseases. Although surgical repair serves as a treatment of choice, it cannot be performed unless weight and anatomical key factors are favorable. The stenting of the right ventricular outflow tract (RVOT) has become an alternative palliative procedure for ToF as an option to alleviate infundibular obstruction with minimal invasion. Methods: A literature search was conducted through 7 databases, followed by the screening and independent assessment of 6 final studies, using the Newcastle-Ottawa Quality Assessment Scale (NOS). Analysis was then conducted using inverse variance analysis, and cumulative data were presented with forest and funnel plots. Results: Studied patients were referred for RVOT stenting due to the marked obstruction of the pulmonary blood flow, a low birth weight, or a small pulmonary artery size. The analysis revealed a significant increase in O2 saturation (mean difference [MD=18%; 13-23.78). The same trend was observed concerning an increase in the Nakata index (MD=54.59; 10.05-99.14), the right pulmonary artery diameter (MD=2.28; 1.20-3.36), and the left pulmonary artery diameter (MD=1.77; 0.22-3.32). Several complications were found, including tricuspid regurgitation and frequent premature beats. Conclusion: RVOT stenting is considered a feasible palliative treatment for ToF, with its high effectiveness in improving patients' condition, especially their pulmonary flow. While complications are scarce, several conditions should be noted, particularly for fatal complications. Finally, this study has limitations as catheterization details in studies and diverse infants' conditions may have caused potential bias.

Strengthening Virology Research in the Association of Southeast Asian Nations: Preparing for Future Pandemics.

The Association of Southeast Asian Nations (ASEAN) region is known to be a global hotspot to viral outbreaks because of many factors. To limit the impact of future outbreaks, it is crucial for the ASEAN governments to strengthen regional virology research capacity. The ASEAN governments have collaborated in several virology initiatives, with the most recent being the establishment of the ASEAN Regional Center for Public Health Emergencies and Emerging Diseases. However, several challenges, including technology disparities, nationalistic tendencies, and the lack of public acceptance toward virus sharing, need to be addressed to maximize the region's collaboration potential in virology research. We recommend the governments to 1) prioritize the strengthening of research capacities; 2) develop stronger cooperation and possible centralization of efforts on top of national capacities; 3) develop an equitable and secure research framework; and 4) improve the public awareness regarding the importance of regional public health responses.

Dengue and COVID-19 infections in the ASEAN region: a concurrent outbreak of viral diseases.

Member countries of the Association of Southeast Asian Nations (ASEAN) have faced dengue outbreaks for decades, and the region has one of the highest rates of dengue globally. Outbreaks continue to occur concurrently with the coronavirus disease 2019 (COVID-19) pandemic in the 10 ASEAN countries. Both infectious diseases pose a tremendous burden in these countries related to both infection control and the economy. Increases in the number of dengue cases occurred in part due to disruptions in the pathogen-host-vector relationship caused by changes in human behaviour in response to the COVID-19 pandemic. The spread of dengue was further aggravated by the implementation of lockdowns and social distancing policies. These measures limited the coverage of dengue preventive programs and delayed the medical management of both diseases due to co-infection and misdiagnosis. It is of the utmost importance for the population to remain aware of both diseases, and dengue vector control strategies must be devised to properly address outbreaks using digitalization and remote surveillance. Similarly, critical triage algorithms and further research are also needed to combat co-infection and misdiagnosis. Controlling the spread of COVID-19 though vaccination should also be undertaken to reduce the impact of the pandemic.