Esophageal achalasia compressing the left atrium and mimicking an extracardiac tumor on the transthoracic echocardiography: A case report.

Achalasia is an uncommon disorder affecting esophageal motility. Occasionally, the appearance of a dilated esophagus in achalasia may resemble an extracardiac tumor when observed through transthoracic echocardiography. Left atrial compression due to extensive esophageal dilation is also rare, potentially leading to hemodynamic compromise. Here, we present a rare case involving left atrial compression caused by esophageal dilation in achalasia, with echocardiographic findings mimicking those of an extracardiac tumor.

Primaquine for uncomplicated Plasmodium vivax malaria in children younger than 15 years: a systematic review and individual patient data meta-analysis.

BACKGROUND: Primaquine, the only widely available treatment to prevent relapsing Plasmodium vivax malaria, is produced as 15 mg tablets, and new paediatric formulations are being developed. To inform the optimal primaquine dosing regimen for children, we aimed to determine the efficacy and safety of different primaquine dose strategies in children younger than 15 years. METHODS: We undertook a systematic review (Jan 1, 2000-July 26, 2024) for P vivax efficacy studies with at least one treatment group that was administered primaquine over multiple days, that enrolled children younger than 15 years, that followed up patients for at least 28 days, and that had data available for inclusion by June 30, 2022. Patients were excluded if they were aged 15 years or older, presented with severe malaria, received adjunctive antimalarials within 14 days of diagnosis, commenced primaquine more than 7 days after starting schizontocidal treatment, had a protocol violation in the original study, or were missing data on age, sex, or primaquine dose. Available individual patient data were collated and standardised. To evaluate efficacy, the risk of recurrent P vivax parasitaemia between days 7 and 180 was assessed by time-to-event analysis for different total mg/kg primaquine doses (low total dose of ∼3·5 mg/kg and high total dose of ∼7 mg/kg). To evaluate tolerability and safety, the following were assessed by daily mg/kg primaquine dose (low daily dose of ∼0·25 mg/kg, intermediate daily dose of ∼0·5 mg/kg, and high daily dose of ∼1 mg/kg): gastrointestinal symptoms (vomiting, anorexia, or diarrhoea) on days 5-7, haemoglobin decrease of at least 25% to less than 7g/dL (severe haemolysis), absolute change in haemoglobin from day 0 to days 2-3 or days 5-7, and any serious adverse events within 28 days. This study is registered with PROSPERO, CRD42021278085. FINDINGS: In total, 3514 children from 27 studies and 15 countries were included. The cumulative incidence of recurrence by day 180 was 51·4% (95% CI 47·0-55·9) following treatment without primaquine, 16·0% (12·4-20·3) following a low total dose of primaquine, and 10·2% (8·4-12·3) following a high total dose of primaquine. The hazard of recurrent P vivax parasitaemia in children younger than 15 years was reduced following primaquine at low total doses (adjusted hazard ratio [HR] 0·17, 95% CI 0·11-0·25) and high total doses (0·09, 0·07-0·12), compared with no primaquine. In 525 children younger than 5 years, the relative rates of recurrence were also reduced, with an adjusted HR of 0·33 (95% CI 0·18-0·59) for a low total dose and 0·13 (0·08-0·21) for a high total dose of primaquine compared with no primaquine. The rate of recurrence following a high total dose was reduced compared with a low dose in children younger than 15 years (adjusted HR 0·54, 95% CI 0·35-0·85) and children younger than 5 years (0·41, 0·21-0·78). Compared with no primaquine, children treated with any dose of primaquine had a greater risk of gastrointestinal symptoms on days 5-7 after adjustment for confounders, with adjusted risks of 3·9% (95% CI 0-8·6) in children not treated with primaquine, 9·2% (0-18·7) with a low daily dose of primaquine, 6·8% (1·7-12·0) with an intermediate daily dose of primaquine, and 9·6% (4·8-14·3) with a high daily dose of primaquine. In children with 30% or higher glucose-6-phosphate dehydrogenase (G6PD) activity, there were few episodes of severe haemolysis following no primaquine (0·4%, 95% CI 0·1-1·5), a low daily dose (0·0%, 0·0-1·6), an intermediate daily dose (0·5%, 0·1-1·4), or a high daily dose (0·7%, 0·2-1·9). Of 15 possibly drug-related serious adverse events in children, two occurred following a low, four following an intermediate, and nine following a high daily dose of primaquine. INTERPRETATION: A high total dose of primaquine was highly efficacious in reducing recurrent P vivax parasitaemia in children compared with a low dose, particularly in children younger than 5 years. In children treated with high and intermediate daily primaquine doses compared with low daily doses, there was no increase in gastrointestinal symptoms or haemolysis (in children with 30% or higher G6PD activity), but there were more serious adverse events. FUNDING: Medicines for Malaria Venture, Bill & Melinda Gates Foundation, and Australian National Health and Medical Research Council.

Rare complications of chronic cholangitis: Pseudoaneurysm of the hepatic artery causing serious gastrointestinal bleeding.

Gastrointestinal bleeding due to hemobilia is a rare condition but can be very serious, even life-threatening. The main causes of biliary bleeding are invasive procedures in treatment, trauma, or malignant diseases. Chronic obstruction of the biliary tract can cause inflammation, erosion, and leakage of adjacent vascular structures and lead to pseudoaneurysm or hemorrhage, but this is very rare. In this article, we present a clinical case of upper gastrointestinal bleeding due to a pseudoaneurysm of the hepatic artery believed to have formed due to chronic cholangitis. An 81-year-old female patient with a medical history of chronic cholangitis was admitted to the hospital with recurrent inflammation accompanied by progressive upper gastrointestinal bleeding, potentially life-threatening. Ultrasound images and blood tests confirmed that the patient had anemia and cholangitis caused by stones. Gastrointestinal endoscopy showed bleeding suspected to be from the biliary tract. Hepatobiliary computed tomography confirmed that the common hepatic artery pseudoaneurysm located at the upper end of the common bile duct had active bleeding.

Geographical variation in patient characteristics and outcomes in heart failure with mildly reduced and preserved ejection fraction.

AIMS: Compared to heart failure (HF) with reduced ejection fraction, HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF) are increasing in prevalence, yet little is known about the geographic variation in patient characteristics, treatments and outcomes among these two HF phenotypes. The aim of this study was to investigate geographic differences in HFpEF and HFmrEF. METHODS AND RESULTS: We conducted an individual patient analysis of five clinical trials enrolling patients with HFpEF or HFmrEF from North America (NA), Latin America (LA), Western Europe (WE), Central/Eastern Europe and Russia (CEER), and Asia-Pacific (AP). We compared regions using descriptive statistics and multivariable regression models. Among the 19 959 patients included, 4066 (23.1%) had HFmrEF and 15 353 (76.9%) HFpEF. Regardless of HF phenotype, patients from WE were oldest, and those in CEER youngest. LA had the largest portion of females and NA most black patients. Obesity and diabetes were most prevalent in NA and hypertension and coronary heart disease most common in CEER. Self-reported health status varied strikingly and was the worst in NA and best in AP. Among patients with HFmrEF, rates of the primary composite endpoint (cardiovascular death or HF hospitalization) were: NA 12.56 per 100 patient-years (/100py), AP 11.67/100py, CEER 10.12/100py, LA 8.90/100py, and WE 8.43/100py, driven by differences in the rate of HF hospitalization. The corresponding values in HFpEF were 11.47/100py, 7.80/100py, 5.47/100py, 5.92/100py, and 7.80/100py, respectively. CONCLUSIONS: There is substantial geographic variation in patient characteristics, treatment and outcomes among patients with HFpEF and HFmrEF. These findings have implications for interpretation and generalizability of trial results, design and conduct of future trials, and optimization of care for these patients.

Conservative versus Surgical Treatment of Pneumatosis Intestinalis: Experience from a Multidisciplinary Center.

BACKGROUND Pneumatosis intestinalis (PI) is an uncommon condition that is not specific to any particular disease. Currently, there is no specific clinical guideline for treating and diagnosing PI. Furthermore, there are numerous causes of PI, which makes it difficult for clinicians - internal medicine physicians as well as surgeons - to take a clinical approach to diagnosis and treatment. CASE REPORT We present 3 clinical scenarios with PI. In the first patient there was a solitary image of PI, which was treated successfully with parenteral nutrition and intravenous antibiotics, and he was discharged after 5 days. The other 2 cases, which involve gas in the hepatic portal vein (HPVG), were handled in 2 distinct ways: surgically and conservatively. One needed diagnostic laparoscopy with necrotic segmentectomy and was discharged from the hospital on postoperative day 16. The last patient, received resuscitation treatment due to severe comorbidities and inability to tolerate surgery. After 3 days, abdominal CT scan revealed no signs of remaining PI. However, the patient was terminally discharged after 7 weeks of treatment due to septic shock caused by sacrococcygeal ulcer and urinary tract infection. By drawing comparisons among these 3 scenarios, we aim to highlight certain indicators for conservative treatment success. CONCLUSIONS PI with HPVG is a sign of severe prognosis, which often requires surgical intervention. However, the decision to manage conservatively or surgically depends on the patient's condition and other criteria such as peritonitis, free fluid in the abdominal cavity, and the presence of shock. Physicians should also weigh the benefits and risks of surgical intervention in critically ill patients.

Effects of Dapagliflozin in Patients in Asia: A Post Hoc Subgroup Analysis From the DELIVER Trial.

Background: Patients with heart failure (HF) with mildly reduced or preserved ejection fraction in Asia may have different clinical characteristics and outcomes compared with patients from other parts of the world. Objectives: The purpose of this study was to investigate the clinical characteristics, safety, and efficacy of dapagliflozin in patients in Asia vs outside Asia in the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trial. Methods: In the DELIVER trial, patients with HF and left ventricular ejection fraction >40% were enrolled across 353 sites in 20 countries. The effects of dapagliflozin vs placebo on primary (composite of worsening HF or cardiovascular death) and secondary outcomes were compared in patients from Asia vs outside Asia. Results: Among 6,263 participants, 1,226 (19.6%) were enrolled in Asia. Participants from Asia were less likely to have diabetes, hypertension, history of myocardial infarction, or obesity. After adjusting for clinically relevant characteristics, those in Asia had similar risks of primary composite outcome compared with those from outside Asia (HR: 0.97; 95% CI: 0.82-1.15). Those in Asia had a lower risk of all-cause mortality compared with those enrolled outside Asia (HR: 0.54; 95% CI: 0.44-0.66). Enrollment from Asia did not modify the effect of dapagliflozin on the primary outcome (Pinteraction = 0.54). Serious adverse events and rates of drug discontinuation were also balanced in both treatment arms, irrespective of enrollment in Asia vs outside Asia. Conclusions: In the global DELIVER trial, dapagliflozin reduced the risk of CV death or worsening HF events and was well tolerated among participants enrolled in both Asia and other geographic regions.

Effect of adherence to primaquine on the risk of Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.

BACKGROUND: Imperfect adherence is a major barrier to effective primaquine radical cure of Plasmodium vivax. This study investigated the effect of reduced adherence on the risk of P. vivax recurrence. METHODS: Efficacy studies of patients with uncomplicated P. vivax malaria, including a treatment arm with daily primaquine, published between January 1999 and March 2020 were identified. Individual patient data from eligible studies were pooled using standardized methodology. Adherence to primaquine was inferred from i) the percentage of supervised doses and ii) the total mg/kg dose received compared to the target total mg/kg dose per protocol. The effect of adherence to primaquine on the incidence of P. vivax recurrence between days 7 and 90 was investigated by Cox regression analysis. RESULTS: Of 82 eligible studies, 32 were available including 6917 patients from 18 countries. For adherence assessed by percentage of supervised primaquine, 2790 patients (40.3%) had poor adherence (≤ 50%) and 4127 (59.7%) had complete adherence. The risk of recurrence by day 90 was 14.0% [95% confidence interval: 12.1-16.1] in patients with poor adherence compared to 5.8% [5.0-6.7] following full adherence; p = 0.014. After controlling for age, sex, baseline parasitaemia, and total primaquine dose per protocol, the rate of the first recurrence was higher following poor adherence compared to patients with full adherence (adjusted hazard ratio (AHR) = 2.3 [1.8-2.9]). When adherence was quantified by total mg/kg dose received among 3706 patients, 347 (9.4%) had poor adherence, 88 (2.4%) had moderate adherence, and 3271 (88.2%) had complete adherence to treatment. The risks of recurrence by day 90 were 8.2% [4.3-15.2] in patients with poor adherence and 4.9% [4.1-5.8] in patients with full adherence; p < 0.001. CONCLUSION: Reduced adherence, including less supervision, increases the risk of vivax recurrence.

Asymptomatic congenital ductus arteriosus aneurysm in a newborn: Case by approach.

A ductus arteriosus aneurysm is a rare congenital lesion with a localized saccular or tubular dilation of the ductus arteriosus. This lesion usually appears in all ages. Some case reports suggest the most common age of diagnosis is less than 2 months. We reported a case of an asymptomatic ductus arteriosus aneurysm in neonates. Echocardiography at 2 days of age revealed a tubular dilation of the ductus arteriosus connected to the pulmonary artery. Computed tomography angiogram showed a ductus arteriosus aneurysm with thrombus at the pulmonary end. It resolved spontaneously in the six months of life without serious complications.

Laparoscopic treatment of Mirizzi syndrome with subtotal cholecystectomy and electrohydraulic lithotripsy: A case report.

Mirizzi syndrome is a rare chronic cholecystitis complication. However, the current consensus on managing this condition remains controversial, especially through laparoscopic surgery. This report describes the feasibility of treating type I Mirizzi syndrome with laparoscopic subtotal cholecystectomy and electrohydraulic lithotripsic gallstone removal. A 53-year-old woman presented with dark urine and right upper quadrant pain for 1 month. On examination, she was jaundiced. Blood tests showed highly elevated liver and biliary enzyme levels. Abdominal ultrasound showed a slightly dilated common bile duct with suspicion of choledocholithiasis. However, endoscopic retrograde cholangiopancreatography showed a narrowed common bile duct extrinsically compressed by a gallstone in the cystic duct, establishing a Mirizzi syndrome diagnosis. Elective laparoscopic cholecystectomy was planned. At operation, the trans-infundibulum approach was used since dissection around the cystic duct was difficult due to severe local inflammation of Calot's triangle. The gallbladder's neck was opened, and the stone was removed by lithotripsy via a flexible choledochoscope. Common bile duct exploration through the cystic duct was normal. The fundus and body of the gallbladder were resected, followed by T-tube drainage and suturing of the gallbladder's neck. The patient's postoperative clinical course was uneventful. Treating Mirizzi syndrome remains a major challenge for hepatobiliary specialists even with open surgery due to high complication rates, including bile duct injuries. Treatment is primarily to clear out the responsible stone and necrotic tissue. Due to advances in endoscopic surgery and equipment, subtotal cholecystectomy with laparoscopic gallstone extraction provides a safe and effective option for patients with Mirizzi syndrome. Laparoscopic subtotal cholecystectomy with electrohydraulic lithotripsy is a feasible and useful approach for treating Mirizzi syndrome that avoids iatrogenic bile duct injury.

Novel Multidisciplinary Approach for Outpatient Antimicrobial Stewardship Using an Emergency Department Follow-Up Program.

Purpose: Outpatient antimicrobial stewardship programs (ASPs) are becoming increasingly prevalent in healthcare. Many programs have demonstrated the effectiveness of pharmacist-driven outpatient consultations or follow-up programs to ensure appropriate antimicrobial prescribing. However, there is a paucity of literature describing multidisciplinary approaches in large healthcare systems for patients discharged from the emergency department (ED). The objective of this study was to describe the feasibility and impact of a combined effort between ASP pharmacotherapy specialists and nurse practitioners (NPs) in managing an ED follow-up center. Methods: A retrospective analysis was conducted for patients discharged from the ED between January 2018 and June 2019. Patients were identified for inclusion based on documentation by ASP pharmacotherapy specialists in the electronic health record for patient-specific inquiries from ED follow-up center NPs. The primary outcome of this study was to describe the number and types of interventions made by ASP pharmacotherapy specialists. Results: A total of 1088 patients were included in the study, for 1114 documented ASP calls. The urinary tract was the most common source of positive culture (79%), and third-generation cephalosporins were the most frequent antibiotic associated with calls (20%). Out of total calls, 60% lead to ASP interventions. Among total calls, the most frequent interventions were to correct drug-bug mismatches (20%), initiate new therapy (10%), and discontinue therapy (7%). Conclusion: This report describes a novel initiative that combines the efforts of ED NPs and ASP pharmacotherapy specialists in managing an ED follow-up center at a large healthcare system.

Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death among patients with chronic heart failure and a left ventricular ejection fraction of 40% or less. Whether SGLT2 inhibitors are effective in patients with a higher left ventricular ejection fraction remains less certain. METHODS: We randomly assigned 6263 patients with heart failure and a left ventricular ejection fraction of more than 40% to receive dapagliflozin (at a dose of 10 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of worsening heart failure (which was defined as either an unplanned hospitalization for heart failure or an urgent visit for heart failure) or cardiovascular death, as assessed in a time-to-event analysis. RESULTS: Over a median of 2.3 years, the primary outcome occurred in 512 of 3131 patients (16.4%) in the dapagliflozin group and in 610 of 3132 patients (19.5%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.92; P<0.001). Worsening heart failure occurred in 368 patients (11.8%) in the dapagliflozin group and in 455 patients (14.5%) in the placebo group (hazard ratio, 0.79; 95% CI, 0.69 to 0.91); cardiovascular death occurred in 231 patients (7.4%) and 261 patients (8.3%), respectively (hazard ratio, 0.88; 95% CI, 0.74 to 1.05). Total events and symptom burden were lower in the dapagliflozin group than in the placebo group. Results were similar among patients with a left ventricular ejection fraction of 60% or more and those with a left ventricular ejection fraction of less than 60%, and results were similar in prespecified subgroups, including patients with or without diabetes. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction. (Funded by AstraZeneca; DELIVER ClinicalTrials.gov number, NCT03619213.).

Whole-genome analysis and secondary metabolites production of a new strain Brevibacillus halotolerans 7WMA2: A potential biocontrol agent against fungal pathogens.

The extensive usage of synthetic fungicides against fungal diseases has caused adverse impacts on both human and agricultural crops. Therefore, the current study aims to establish a new bacterium 7WMA2, as a biocontrol agent to achieve better antifungal results. The strain 7WMA2 was isolated from marine sediment, displayed a broad spectrum of several fungi that includes Alternaria alternata, Cladosporium sp., Candida albicans, Fusarium oxysporum, Trichosporon pullulans, and Trichophyton rubrum. The 16S rRNA phylogeny inferred that strain 7WMA2 was a member of Brevibacillus. The phylogenetic and biochemical analyses revealed that the strain 7WMA2 belongs to the species of Brevibacillus halotolerans. The complete genome sequence of Brevibacillus halotolerans 7WMA2 consists of a circular chromosome of 5,351,077 bp length with a GC content of 41.39 mol %, including 4433 CDS, 111 tRNA genes, and 36 rRNA genes. The genomic analysis showed 23 putative biosynthetic secondary metabolite gene clusters responsible for non-ribosomal peptides, polyketides and siderophores. The antifungal compounds concentrated from cell-free fermentation broth demonstrated strong inhibition of fungi, and the compounds are considerably thermal stable and adaptable to pH range 2-12. This complete genome sequence has provided insight for further exploration of antagonistic ability and its secondary metabolite compounds indicated feasibility as biological control agents against fungal infections.

Frequency equation and semi-empirical mechanical coupling strength of microcantilevers in an array.

A characteristic equation for the frequencies of the T-shaped and overhang-shaped cantilevers is derived for the first time. We show that there are optimum values of the overhang lengths and widths that maximize the frequency and the number of maxima is corresponding to the mode number. The frequency of higher-order modes could be tuned by changing the overhang dimensions. Especially, a semi-empirical formula for the coupling strength κ between cantilevers in an array is proposed where the strength presents a cubic decrease with the overhang width ξ and a linear increase with the overhang length η , κ = η / ξ 3 . There is a very good agreement between the proposed formula and the values obtained in recent experiments by other researchers.

Ultrasound Imaging of Pancreatic Perfusion Dynamics Predicts Therapeutic Prevention of Diabetes in Preclinical Models of Type 1 Diabetes.

In type 1 diabetes (T1D), immune-cell infiltration into islets of Langerhans (insulitis) and ß-cell decline occur years before diabetes presents. There is a lack of validated clinical approaches for detecting insulitis and ß-cell decline, to diagnose eventual diabetes and monitor the efficacy of therapeutic interventions. We previously determined that contrast-enhanced ultrasound measurements of pancreas perfusion dynamics predict disease progression in T1D pre-clinical models. Here, we test whether these measurements predict therapeutic prevention of T1D. We performed destruction-reperfusion measurements with size-isolated microbubbles in non-obese diabetic (NOD)-severe combined immunodeficiency (SCID) mice receiving an adoptive transfer of diabetogenic splenocytes. Mice received vehicle control or the following treatments: (i) anti-CD3 to block T-cell activation; (ii) anti-CD4 to deplete CD4+ T cells; (iii) verapamil to reduce ß-cell apoptosis; or (iv) tauroursodeoxycholic acid (TUDCA) to reduce ß-cell endoplasmic reticulum stress. We compared measurements of pancreas perfusion dynamics with subsequent progression to diabetes. Anti-CD3, anti-CD4, and verapamil delayed diabetes development. Blood flow dynamics was significantly altered in treated mice with delayed/absent diabetes development compared with untreated mice. Conversely, blood flow dynamics in treated mice with unchanged diabetes development was similar to that in untreated mice. Thus, measurement of pancreas perfusion dynamics predicts the successful prevention of diabetes. This strategy may provide a clinically deployable predictive marker for therapeutic prevention in asymptomatic T1D.

Morpho-Anatomical Study And Botanical Identification of Pogostemon auricularius (L.) Hassk. (Lamiaceae).

Pogostemon Desf. includes a wide range of taxa found in subtropical and tropical areas. Few works, however, have studied microanatomical characteristics of Pogostemon species and as yet identified features of Pogostemon auricularius (L.) Hassk. Thus, in this paper, we examined the taxonomic implications of root, stem and leaf morphology for species P. auricularius collected from Quang Tri Province. Light microscopy was mainly used in our study. Qualitative characters like stem quadrangular, hirsute; leaves opposite, ovate, margin serrulate; calyx campanulate; corolla small with separate equal lobes have been found in P. auricularius. Epidermal anatomy on the aerial parts of the species like epidermal cell shape, anticlinal walls, trichomes types, stomata types and calcium oxalate crystals types were examined as well. Quantitative characters like the length and width of leaf blade and inflorescence; the size of oil droplet, stomata and calcium oxalate crystals measured provided taxonomic significance. Based on identifying morphological characteristics of P. auricularius, we aimed to contribute to the taxonomic investigation into the genus Pogostemon and give relative morphological and microanatomical features compared with other taxa.

Application of machine learning in screening for congenital heart diseases using fetal echocardiography.

There is a growing body of literature supporting the utilization of machine learning (ML) to improve diagnosis and prognosis tools of cardiovascular disease. The current study was to investigate the impact that the ML framework may have on the sensitivity of predicting the presence or absence of congenital heart disease (CHD) using fetal echocardiography. A comprehensive fetal echocardiogram including 2D cardiac chamber quantification, valvar assessments, assessment of great vessel morphology, and Doppler-derived blood flow interrogation was recorded. The postnatal echocardiogram was used to ascertain the diagnosis of CHD. A random forest (RF) algorithm with a nested tenfold cross-validation was used to train models for assessing the presence of CHD. The study population was derived from a database of 3910 singleton fetuses with maternal age of 28.8 ± 5.2 years and gestational age at the time of fetal echocardiography of 22.0 weeks (IQR 21-24). The proportion of CHD was 14.1% for the studied cohort confirmed by post-natal echocardiograms. Our proposed RF-based framework provided a sensitivity of 0.85, a specificity of 0.88, a positive predictive value of 0.55 and a negative predictive value of 0.97 to detect the CHD with the mean of mean ROC curves of 0.94 and the mean of mean PR curves of 0.84. Additionally, six first features, including cardiac axis, peak velocity of blood flow across the pulmonic valve, cardiothoracic ratio, pulmonary valvar annulus diameter, right ventricular end-diastolic diameter, and aortic valvar annulus diameter, are essential features that play crucial roles in adding more predictive values to the model in detecting patients with CHD. ML using RF can provide increased sensitivity in prenatal CHD screening with very good performance. The incorporation of ML algorithms into fetal echocardiography may further standardize the assessment for CHD.

The frequency of the known mitochondrial variants associated with drug-induced toxicity in a Korean population.

BACKGROUND: Few studies have annotated the whole mitochondrial DNA (mtDNA) genome associated with drug responses in Asian populations. This study aimed to characterize mtDNA genetic profiles, especially the distribution and frequency of well-known genetic biomarkers associated with diseases and drug-induced toxicity in a Korean population. METHOD: Whole mitochondrial genome was sequenced for 118 Korean subjects by using a next-generation sequencing approach. The bioinformatic pipeline was constructed for variant calling, haplogroup classification and annotation of mitochondrial mutation. RESULTS: A total of 681 variants was identified among all subjects. The MT-TRNP gene and displacement loop showed the highest numbers of variants (113 and 74 variants, respectively). The m.16189T > C allele, which is known to reduce the mtDNA copy number in human cells was detected in 25.4% of subjects. The variants (m.2706A > G, m.3010A > G, and m.1095T > C), which are associated with drug-induced toxicity, were observed with the frequency of 99.15%, 30.51%, and 0.08%, respectively. The m.2150T > A, a genotype associated with highly disruptive effects on mitochondrial ribosomes, was identified in five subjects. The D and M groups were the most dominant groups with the frequency of 34.74% and 16.1%, respectively. CONCLUSIONS: Our finding was consistent with Korean Genome Project and well reflected the unique profile of mitochondrial haplogroup distribution. It was the first study to annotate the whole mitochondrial genome with drug-induced toxicity to predict the ADRs event in clinical implementation for Korean subjects. This approach could be extended for further study for validation of the potential ethnic-specific mitochondrial genetic biomarkers in the Korean population.

Development of population pharmacokinetics model of isoniazid in Indonesian patients with tuberculosis.

OBJECTIVES: No population pharmacokinetics (PK) model of isoniazid (INH) has been reported for the Indonesian population with tuberculosis (TB). Therefore, we aimed to develop a population PK model to optimize pharmacotherapy of INH on the basis of therapeutic drug monitoring (TDM) implementation in Indonesian patients with TB. MATERIALS AND METHODS: INH concentrations, N-acetyltransferase 2 (NAT2) genotypes, and clinical data were collected from Dr. Soetomo General Academic Hospital, Indonesia. A nonlinear mixed-effect model was used to develop and validate the population PK model. RESULTS: A total of 107 patients with TB (with 153 samples) were involved in this study. A one-compartment model with allometric scaling for bodyweight effect described well the PK of INH. The NAT2 acetylator phenotype significantly affected INH clearance. The mean clearance rates for the rapid, intermediate, and slow NAT2 acetylator phenotypes were 55.9, 37.8, and 17.7 L/h, respectively. Our model was well-validated through visual predictive checks and bootstrapping. CONCLUSIONS: We established the population PK model for INH in Indonesian patients with TB using the NAT2 acetylator phenotype as a significant covariate. Our Bayesian forecasting model should enable optimization of TB treatment for INH in Indonesian patients with TB.

Echocardiographic Reference Ranges of Non-invasive Myocardial Work Indices in Children.

Global myocardial work (GMW) is an emerging method to characterize left ventricle (LV) function with potential advantages over both ejection fraction and global longitudinal strain (GLS). We aimed to determine the feasibility and reproducibility for echocardiographic-derived GMW in a healthy pediatric population; establish normal reference values; and investigate the influence of age, gender, and other clinical factor on normal reference ranges. We prospectively enrolled 212 individuals (median age of 9 years; interquartile range, 6 to 12 years, 112 female). Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were measured from LV pressure-strain loops. Quantification of GMW was performed using a GE Vivid E95 system and available software package (Echopac V.203, GE). The mean LV EF was 64 ± 3% with GLS of -21.3 ± 1.5%. GWI was 1688 ± 219 mmHg% with mean GWE of 96.5 ± 1.4%. The GCW was 1959 ± 207 mmHg%, and the mean GWW of 61.1 ± 30.9 mmHg%. No significant difference was found in MW indices across age group and gender (p > 0.05 for all). There were significant correlations between both GWI and GCW with GLS and systolic blood pressure (p < 0.001), but not with GWE and GWW. Linear regression model revealed that GWI and GCW were more closely correlated with systolic blood pressure than GLS. LV MW indices had good intra-observer and inter-observer reproducibility. This study establishes both the feasibility and reference ranges for non-invasive echocardiographic indices of GMW in healthy children. Myocardial work appears to be a complementary modality to assess LV performance in children.