Eastern Asian Population Research Articles

A nomogram incorporating Psoas muscle index for predicting tumor recurrence after liver transplantation: A retrospective study in an Eastern Asian population

Background and aimsTumor recurrence significantly affects the prognostic outcomes for liver cancer patients following liver transplantation. However, existing predictive models often neglect the inclusion of body composition indicators. Hence, this research aimed to investigate the significance of the psoas muscle index (PMI) in evaluating the post-transplant prognosis of liver cancer. MethodsA retrospective analysis was conducted on liver cancer patients who underwent liver transplantation surgery. Imaging analysis was performed using CT data to calculate PMI based on the left and right psoas muscle areas. Subsequently, the patients were categorized into PMI-Low and PMI-High groups using the established cut-off values. Univariate and multivariate analyses were performed using Cox proportional hazards regression to assess the correlation between PMI and clinical outcomes, and a nomogram was constructed accordingly. ResultsAmong the 225 patients included in the analysis, the PMI-High group exhibited significantly improved overall survival (P < 0.001) and disease-free survival (DFS, P < 0.001) rates compared to the PMI-Low group. PMI exhibited a positive correlation with body mass index (R = 0.25, P < 0.001), but no significant correlations were observed. In the multivariate analysis, PMI (HR = 4.596, P < 0.001), MELD score (HR = 1.591, P = 0.038), and Hangzhou criteria (HR = 2.557, P < 0.001) emerged as significant predictors of DFS. The constructed nomogram, incorporating these predictors, demonstrated outstanding predictive performance. Decision curve analysis revealed the superiority of the nomogram over conventional methods. ConclusionsPMI serves as a valuable prognostic factor for tumor recurrence in liver cancer patients after liver transplantation. The established nomogram is pivotal in delivering personalized predictions of DFS.

Real-World Effectiveness and Safety of Ramucirumab as a Second-Line Treatment for Patients with Unresectable Advanced or Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma in Japan and South Korea: A Systematic Literature Review.

Gastric cancer has the highest incidence and mortality in Eastern Asia. The efficacy and safety of ramucirumab (RAM) monotherapy or in combination with paclitaxel (PTX) for patients with unresectable advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (G/GEA) have been established in clinical trials. To assess the effectiveness and safety of RAM or RAM-based therapy as a second-line treatment in real-world clinical practice in Eastern Asia and to pave the way for future research, a systematic literature review (SLR) was conducted. Studies published between January 2014 and December 2021 were identified in PubMed, Embase, Cochrane Library, CNKI, Wanfang, and CBM databases. This SLR included 23 studies from Japan and South Korea, of which 22 were retrospective and 11 were full-text articles. Most studies investigated RAM + PTX (range of median overall survival [mOS] 7.4-12.2months; median progression-free survival [mPFS] 3.35-7.0months). Data were limited for RAM, RAM + albumin-bound paclitaxel, and RAM + taxane. RAM + PTX was associated with longer survival (mOS 9.3-12.2months vs. 5.2-9.7months; mPFS 4.1-5.1months vs. 3.0-4.1months) than PTX. Patients with prior anti-programmed cell death1 (anti-PD-1) exposure experienced longer mPFS (4.8 vs. 3.4months) from RAM + taxane than those without prior anti-PD-1 exposure. Few patients (3.3-6.3%) discontinued RAM or RAM-based therapy because of adverse events (AEs). Hematological toxicities were most frequently occurring AEs and no new safety signals were identified compared to clinical trials. RAM + PTX as a second-line treatment is effective and associated with an acceptable toxicity profile in patients with advanced or metastatic G/GEA in real-world settings of Japan and South Korea. More studies are recommended to further evaluate effectiveness and safety of RAM or RAM-based therapy, especially after anti-PD-1 therapy, in a wider Eastern Asian population. INPLASY registration number INPLASY2022120023.

FRI550 Case Of Thyrotoxic Periodic Paralysis In African American Man With Cannabis Use

Abstract Disclosure: H. Al Jumaili: None. A. Mahaldar: None. S. Campbell: None. A. Gosmanova: None. Introduction: Recent changes in cannabis use (CU) laws led to growing interest in its use for recreational and therapeutic purposes. may have serious health problems such as hypokalemia, paralysis and rhabdomyolysis. Thyrotoxic Periodic Paralysis (TPP) is a rare and life-threatening complication of the thyrotoxicosis characterized by acute reversable painless muscle weakness or paralysis and hypokalemia due to massive intracellular shift of potassium. This condition is mainly seen males of Asian descent. Case: A 31-year-old African American man with Graves’ disease admitted to the hospital for upper and lower extremities weakness after Thanksgiving Day. He woke up with sudden inability to move any of his extremities with. He had high carbohydrate meal, on the evening. Patient reported having similar periodic episodes of paralysis, usually worse in the lower extremities for the last 2 years. This episode lasted longer than usual. On exam, he had enlarged thyroid gland and tachycardia. motor weakness, worse on lower extremities, hyporeflexia and intact sensation. Potassium was 1.8 mmol/l, magnesium 1.5 mg/dl, TSH &amp;lt;0.01 mIU/ml, FT4 4.3 ng/dl, FT3 18.3 ng/dl, anti-thyroid antibodies were elevated at 18 IU/L, and urine screen was positive for cannabinoid. Potassium was replaced, he was given propranolol and continued on methimazole. Patient's paralysis had improved in all four limbs, with serum potassium of 4.1 mmol/L. Discussion: TPP is a rarely seen condition in US but is known in an eastern Asian population, and in US the incidence rate was reported to be around 0.1 to 0.2%. American Indian are thought to be the higher risk. Underlying mechanism is imbalance in potassium homeostasis due to increased cellular Na-K ATPase pump activity with shift of potassium to the intracellular space. There are many theories regarding the cause of exaggerated intracellular potassium influx in TPP. Na-K ATPase activity is directly stimulated by thyroid hormone and insulin response to carbohydrate ingestion which promotes potassium uptake into muscle correlating with clinical observation that paralysis seen after a high carbohydrate meal. KCNJ18 gene mutations which alter the function of an inwardly rectifying potassium channel named Kir2.6 have been detected in some patients. In our patient, additional factor such as cannabis use potentiated intracellular potassium shift and hypokalemia. Recent evidence suggests that the CB1 receptor is expressed not only in the brain, but also found in lungs, heart, and skeletal muscle. Stimulation of (CB1) and activation of G protein-coupled inwardly rectifying potassium (GIRK) channels through intra-cellular signal cascades promotes hypokalemia and paralysis. Conclusion: This case raises awareness of TPP in non-Asian population and highlights the importance to consider cannabis as additional trigger for hypokalemia and paralysis. Presentation: Friday, June 16, 2023

Five-Year Physical and Psychosocial Outcomes in Obese Adolescents With and Without Metabolic Bariatric Surgery

PurposeMetabolic bariatric surgery (MBS) is increasingly accepted as a treatment for severely obese adolescents. However, its long-term efficacy and safety are not well characterized, particularly in the Eastern Asian population. We aimed to explore the long-term effects of MBS on Chinese adolescents with severe obesity. MethodsA total of 44 obese adolescents (≤18 years old) underwent MBS at our institution from May 2011 to May 2017. A matched nonsurgical control group, including 43 patients, was recruited from lifestyle modification programs in the same period. All patients completed assessments at presurgery/baseline and five years after surgery. The data were collected and analyzed using the χ2 test and an independent sample t-test. ResultsComparing the surgical and control groups revealed that the surgical patients showed significant weight loss and improvement in comorbidities, while the nonsurgical patients showed a trend of weight gain and increased comorbidities (p < .05). Furthermore, the surgical patients had a higher composite physical quality of life (as determined by the Short Form-36 questionnaire). On the other hand, the patients who underwent MBS had a higher risk of malnutrition. DiscussionCompared with nonsurgical patients, severely obese adolescents who undergo MBS exhibit more effective long-term weight loss, remission of comorbidities, and improved quality of life. Furthermore, more attention should be paid to helping adolescents avoid malnutrition after they undergo MBS.

Parameters of Iliopsoas Plane Immediately Caudal to the Indirect Tendon of Rectus Femoris in Axial Plane Measured on Magnetic Resonance Images in an Adult Eastern Asian Population.

The iliopsoas plane (IP) is a fascial plane deep to the iliopsoas complex and is the target of several novel ultrasound-guided analgesic interventions for hip. Currently, limited information is known about its parameters. From the pelvic magnetic resonance (MR) images of an adult Eastern Asian population (n = 49), the IP width, depth, and needle-beam angle in the axial plane immediately caudal to the level of indirect tendon of rectus femoris (RF) were found to be 10.7 ± 1.6 mm, 48.5 ± 15.5 mm, and 84.2 ± 8.2 degrees, respectively. There was a statistically significant difference in the age categories for IP width, and older patients seemed to have wider IP. Our data may provide applications for the technical modification of ultrasound-guided iliopsoas plane block (IPB) in acute hip pain management and the future development of ultrasound-guided single-needle-entry radiofrequency neuroablation in chronic hip pain management.

Lobular Difference in Heritability of Brain Atrophy among Elderly Japanese: A Twin Study.

Background and Objectives: Brain atrophy is related to cognitive decline. However, the heritability of brain atrophy has not been fully investigated in the Eastern Asian population. Materials and Methods: Brain imaging of 74 Japanese twins registered in the Osaka University Twin Registry was conducted with voxel-based morphometry SPM12 and was processed by individual voxel-based morphometry adjusting covariates (iVAC) toolbox. The atrophy of the measured lobes was obtained by comparing the focal volume to the average of healthy subjects. Classical twin analysis was used to measure the heritability of its z-scores. Results: The heritability of brain atrophy ranged from 0.23 to 0.97, depending upon the lobes. When adjusted to age, high heritability was reported in the frontal, frontal-temporal, and parietal lobes, but the heritability in other lobes was lower than 0.70. Conclusions: This study revealed a relatively lower heritability in brain atrophy compared to other ethnicities. This result suggests a significant environmental impact on the susceptibility of brain atrophy the Japanese. Therefore, environmental factors may have more influence on the Japanese than in other populations.

The effect of polymorphisms (M235T and T174M) on the angiotensinogen gene (AGT) in coronary artery disease in the Eastern Asian population: A systematic review and meta-analysis.

Background:It is thought that genetic factors may play an important role in the development of coronary artery disease (CAD). Several studies report that AGT polymorphism is implicated in CAD susceptibility, but these results contradict those of the other studies with the associations being unclear in the Eastern Asian population. Therefore, meta-analysis was performed to evaluate this relationship.Methods:Publication databases were used to search for eligible relevant studies and valid data were extracted from studies meeting the inclusion criteria. Subsequently, odds ratios (ORs) with 95 % confidence intervals (CIs), were used to assess the strength of the association between AGT polymorphism and CAD risk.Results:Seven eligible studies published only in English were included in the present meta-analysis. In the Eastern Asian population, CAD susceptibility was shown to be related to AGT M235T under the heterozygote model (OR = 0.19). Stratified analysis indicated there was a significant relationship between AGT M235T and CAD risk in China under allelic (OR = 1.34), dominant (OR = 1.43), and heterozygote (OR = 1.62) models. The results showed that the T174M polymorphism was significantly associated with CAD risk in recessive (OR = 2.28) and homozygote (OR = 2.37) models in the Eastern Asian population.Conclusions:In the Eastern Asian population, especially the Chinese, the M235T of AGT is associated with CAD susceptibility. The T174M polymorphisms were associated with CAD risk in the Eastern Asian population.

CT psoas calculations on the prognosis prediction of emergency laparotomy: a single-center, retrospective cohort study in eastern Asian population

BackgroundEmergency laparotomy (EL) has a high mortality rate. Clinically, frail patients have a poor tolerance for EL. In recent years, sarcopenia has been used as an important indicator of frailty and has received much attention. There have been five different calculation methods of psoas for computed tomography (CT) to measure sarcopenia, but lack of assessment of these calculation methods in Eastern Asian EL patients.MethodsWe conducted a 2-year retrospective cohort study of patients over 18 years of age who underwent EL in our institution. Five CT measurement values (PMI: psoas muscle index, PML3: psoas muscle to L3 vertebral body ratio, PMD: psoas muscle density, TPG: total psoas gauge, PBSA: psoas muscle to body face area ratio) were calculated to define sarcopenia. Patients with sarcopenia defined by the sex-specific lowest quartile of each measurement were compared with the rest of the cohort. The primary outcome was "ideal outcome", defined as: (1) No postoperative complications of Clavien-Dindo Grade ≥ 4; (2) No mortality within 30 days; (3) When discharged, no need for fluid resuscitation and assisted ventilation, semi-liquid diet tolerated, and able to mobilize independently. The second outcome was mortality at 30-days. Multivariate logistic regression and receiver operating characteristic (ROC) analysis were used.ResultsTwo hundred and twenty-eight patients underwent EL met the inclusion criteria, 192 (84.2%) patients had an ideal outcome after surgery; 32 (14%) patients died within 30 days. Multivariate analysis showed that, except PMD, each calculation method of psoas was independently related to clinical outcome (ideal outcome: PML3, P < 0.001; PMI, P = 0.001; PMD, P = 0.157; TPG, P = 0.006; PBSA, P < 0.001; mortality at 30-days: PML3, P < 0.001; PMI, P = 0.002; PMD, P = 0.088; TPG, P = 0.002; PBSA, P = 0.001). In ROC analysis, the prediction model containing PML3 had the largest area under the curve (AUC) value (AUC value = 0.922 and 0.920, respectively).ConclusionThe sarcopenia determined by CT psoas measurements is significantly related to the clinical outcome of EL. The calculation of CT psoas measurement is suitable for application in outcome prediction of EL. In the future, it is necessary to develop a scoring tool that includes sarcopenia to evaluate the risk of EL better.

Comprehensive Analysis of Somatic Reversion Mutations in Homologous Recombination Repair (HRR) Genes in A Large Cohort of Chinese Pan-cancer Patients.

Purpose: Mutations leading to homologous recombination deficiency (HRD) increase the tumor sensitivity to platinum-based chemotherapy and PARP inhibitors. However, reversion mutations often develop conferring acquired drug resistance. There is still a lack of comprehensive investigation on HRR reversion mutations in large pan-cancer cohorts, especially in the Eastern Asian population. This study aims to characterize reversion mutations in homologous recombination repair (HRR)-related genes in a large cohort of Chinese pan-cancer patients.Methods: Sequencing data from 23,375 patients across over 17 cancer types were retrospectively analyzed for pathogenic/likely pathogenic (P/LP) germline mutations in 15 HRR genes. Somatic mutations detected in tumor or circulating cell-free DNA predicted to restore the open reading frame of the deleterious allele were subsequently identified as reversion mutations.Results: 654 cases out of 23,375 (2.8%) unselected pan-cancer patients were identified with HRR germline mutations. Secondary somatic mutations were further analyzed in their matched tumor/plasma samples. The overall frequency of reversion mutation was 1.7% (11/654). The reversion mutations occurred only in 3 out of the 15 HRR genes: BRCA1 (3.8%), BRCA2 (3.5%) and PALB2 (2.0%) from 11 patients (6 breast cancers, 1 ovarian cancer, 1 pancreatic cancer, 1 lung cancer and 2 breast and ovarian dual cancers). We identified total 25 reversion events (BRCA1, n=9; BRCA2, n=8; PALB2, n=8), including 12 pure deletions, 10 missense single nucleotide variants, 2 insertions and 1 splice site mutation. Besides, we detected microhomology length >1bp in seven out of the reversion deletions (58.3%), suggestive of microhomology-mediated end-joining (MMEJ) repair signature. Intriguingly, a positive correlation (r=0.85, p=0.001) between the length of deletion and the microhomology length was also observed. We obtained disease courses from 6/11 patients with reversion events. Four acquired reversions after the failure of the PARP inhibitor treatment. Two patients had somatic reversion mutations identified after progressing on platinum-based treatment.Conclusion: This study comprehensively depicts the prevalence and characteristics of HRR reversion mutation of germline mutations in an unselected Chinese pan-cancer cohort. The reversion mutations predominantly occurred in BRCA1, BRCA2 and PALB2. The results revealed that reversion mutations frequently occurred after resistance to platinum-based chemotherapy and/or PARP inhibitor. Our study provides insight into the underlying mechanism of drug resistance in HRD tumors and suggests that monitoring HRR mutation status along the disease course could be beneficial especially for informing resistance mechanisms and guiding subsequent therapies.

Efficacy and Cardiovascular Safety of Alpha Glucosidase Inhibitors.

Alpha Glucosidase Inhibitors (AGIs) are a group of drugs which act on the gastrointestinal tract and help in reducing fasting and postprandial hyperglycemia by reducing the absorption of carbohydrates. This group comprises Acarbose, Miglitol and Voglibose. They are available on the market for almost three decades now. When used as monotherapy, Glycated Haemoglobin (HbA1c) reduction can be as high as 0.77%, which is predominantly noted in the Eastern Asian population and those on a high carbohydrate diet. There is a more pronounced reduction in HbA1c in those who present with higher baseline values. Despite not showing a significant cardiovascular benefit with regards to mortality and morbidity, they have proven to be a safe class of drugs which can be used in patients not tolerating various other anti-diabetic agents due to their local site of action and poor systemic absorption. Though they are available worldwide, AGIs are used more often in the Far East and South Asia. They have shown benefits in reducing the development of diabetes when used in those with impaired glucose tolerance or pre-diabetes. They have been shown to improve postprandial hyperglycemia, which in itself is an independent risk factor for cardiovascular morbidity. These have proven their safety from both cardiovascular and non-cardiovascular perspectives and can be combined with any class of anti-diabetic agents. They are not favoured in most of the current Western Guidelines due to their modest HbA1c reduction, neutrality with cardiovascular benefit as well as their significant gastrointestinal side effect profile.

Biochemical Markers and Alterations in Keratoconus.

Keratoconus (KC) is a corneal ectatic condition characterized by focal structural changes, resulting in progressive thinning, biomechanical weakening, and steeping of the cornea that can lead to worsening visual acuity due to irregular astigmatism and corneal scarring in more advanced cases. It is a relatively common ectatic disease of the cornea predominantly affecting the younger population. Despite its worldwide prevalence, its incidence is rather varied with a higher incidence among the Middle Eastern and South Asian population. Dysregulated corneal extracellular matrix remodeling underlies KC pathogenesis. However, a lack of absolute clarity regarding the factors that initiate and drive progression poses a significant challenge in its prevention and management. KC is a complex multifactorial disease as it is associated with a wide variety of etiological factors such as environmental stimuli/insults, oxidative stress, genetic predisposition, comorbidities, and eye rubbing. A series of studies using corneal tissues (epithelium, stroma), cultured corneal fibroblasts/keratocytes, tear fluid, aqueous humor, and blood from KC subjects has reported significant alterations in various biochemical factors such as extracellular matrix components, cellular homeostasis regulators, inflammatory factors, hormones, metabolic products, and chemical elements. It has become apparent that alterations in the biochemical mediators (related to various etiologies) could contribute to KC pathogenesis by altering the dynamics of extracellular matrix remodeling events such as collagen deposition, degradation, and cross-linking in the cornea. Determining key disease contributing biochemical mediators would aid in disease monitoring, prediction or abatement of disease progression, and development of targeted therapeutics to improve disease prognosis.

Determinants of Breast-Conserving Therapy in the Asian Population: A Systematic Review.

Treatment guidelines recommend breast-conserving therapy (BCT) for patients with early-stage breast cancer. However, Asian patients choose mastectomy over BCT, and the factors influencing this choice are unknown. This review aimed to identify the factors most frequently reported in the Eastern and Southeastern Asian population influencing the choice of BCT for treatment of early-stage breast cancer. PRISMA guidelines were followed, and PubMed and EMBASE databases were used. The literature search initially identified 4619 articles; abstract screening and full-text screening were performed on 150 and 19 articles, respectively, and 9 articles were finally included in the study. Selection of BCT was associated with sociodemographic factors, such as high socioeconomic status and education level and young age at diagnosis; clinicopathological factors, such as small tumor size and mammographically detected tumors; and healthcare provider factors, such as treatment from a female doctor or from a breast specialist. However, not selecting BCT was associated with personal factors, such as fear of recurrence and avoidance of further treatment. The process of making a treatment decision is complicated and involves many factors influencing patients' choice of surgery type. Exploring these factors helps to elucidate why patients do not choose BCT as their treatment option.

Host Genetic Variants Potentially Associated With SARS-CoV-2: A Multi-Population Analysis.

BackgroundClinical outcomes of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) showed enormous inter-individual and inter-population differences, possibly due to host genetics differences. Earlier studies identified single nucleotide polymorphisms (SNPs) associated with SARS-CoV-1 in Eastern Asian (EAS) populations. In this report, we aimed at exploring the frequency of a set of genetic polymorphisms that could affect SARS-CoV-2 susceptibility or severity, including those that were previously associated with SARS-CoV-1.MethodsWe extracted the list of SNPs that could potentially modulate SARS-CoV-2 from the genome wide association studies (GWAS) on SARS-CoV-1 and other viruses. We also collected the expression data of these SNPs from the expression quantitative trait loci (eQTLs) databases. Sequences from Qatar Genome Programme (QGP, n = 6,054) and 1000Genome project were used to calculate and compare allelic frequencies (AF).ResultsA total of 74 SNPs, located in 10 genes: ICAM3, IFN-γ, CCL2, CCL5, AHSG, MBL, Furin, TMPRSS2, IL4, and CD209 promoter, were identified. Analysis of Qatari genomes revealed significantly lower AF of risk variants linked to SARS-CoV-1 severity (CCL2, MBL, CCL5, AHSG, and IL4) compared to that of 1000Genome and/or the EAS population (up to 25-fold change). Conversely, SNPs in TMPRSS2, IFN-γ, ICAM3, and Furin were more common among Qataris (average 2-fold change). Inter-population analysis showed that the distribution of risk alleles among Europeans differs substantially from Africans and EASs. Remarkably, Africans seem to carry extremely lower frequencies of SARS-CoV-1 susceptibility alleles, reaching to 32-fold decrease compared to other populations.ConclusionMultiple genetic variants, which could potentially modulate SARS-CoV-2 infection, are significantly variable between populations, with the lowest frequency observed among Africans. Our results highlight the importance of exploring population genetics to understand and predict COVID-19 outcomes. Indeed, further studies are needed to validate these findings as well as to identify new genetic determinants linked to SARS-CoV-2.

Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese Family

Purpose To screen out pathogenic genes in a Chinese family with congenital cataract and iris coloboma. Material and Methods. A three-generation family with congenital cataract and iris coloboma from a Han ethnicity was recruited. DNA was extracted from peripheral blood samples collected from all individuals in the family. Whole exon sequencing was employed for screening the disease-causing gene mutations in the proband, and Sanger sequencing was used for other members of the family and a control group of 500 healthy individuals. Bioinformatics analysis and three-dimensional structure predictions were used to predict the impact of amino acid changes on protein structure and function. Results The candidate genes of cataract and iris coloboma were successfully screened out. A heterozygote mutation, CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, Conclusions We report a novel mutation, WFS1 p.C505S, and a known mutation, CRYGD p.P24T, that cosegregate with iris coloboma and congenital cataract, respectively, in a Chinese family. This is the first time the association of WFS1 p.C505S with iris coloboma has been demonstrated, although CRYGD p.P24T has been widely reported as being associated with congenital cataract, especially in the Eastern Asian population. These findings may have future therapeutic benefit for the diagnosis of iris coloboma and congenital cataract. The results may also be relevant in further studies aiming to investigate the molecular pathogenesis of iris coloboma and congenital cataract.WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation,

Suzuki Toru, “Eastern Asian Population History and Contemporary Population Issues” Springer, Springer Briefs in Population Studies, Population Studies of Japan, 2019, 84p

Suzuki Toru, “Eastern Asian Population History and Contemporary Population Issues” Springer, Springer Briefs in Population Studies, Population Studies of Japan, 2019, 84p

A Combination of the Mayo Adhesive Probability Score and the RENAL Score to Predict Intraoperative Complications in Small Renal Masses

Introduction: To evaluate the potential predictive value of the Mayo Adhesive Probability (MAP) score combined with the RENAL score for intraoperative outcomes in retroperitoneal laparoscopic nephron-sparing surgery (NSS) in an Eastern Asian population. Methods: An initial of 388 patients undergoing retroperitoneal laparoscopic NSS were identified. MAP and RENAL scores were calculated according to CT and a logistic regression model was adopted as a combination of the RENAL score and the MAP score. Results: A total of 293 patients were included. The overall intraoperative complication rate was 7.5% (21 cases). The MAP score was found to correlate with operation time (OT; r = 0.169), estimated blood loss (EBL; r = 0.318), and intraoperative complications (r = 0.242). The RENAL score was correlated with warm is­chemia time (r = 0.503), OT (r = 0.334), intraoperative complications (r = 0.178), and EBL (r = 0.218). The MAP score and the RENAL score were reliable predictors of overall intraoperative complications, with areas under the curve (AUC) of 0.728 and 0.759, respectively. After combination of these 2 scores, the AUC of overall intra-operative complications was improved with statistical significance (AUC = 0.847, combination vs. RENAL score: p = 0.044 < 0.05; combination vs. MAP score: p = 0.005 < 0.05). Conclusion: The MAP score is an important predictor of EBL, OT, and intraoperative complications in retroperitoneal laparoscopic NSS and its combination with the RENAL score showed a superior predictive value compared to a single score in overall intraoperative complications. The MAP score might be considered in preoperative radiologic aspects as regularly as the RENAL score.

Prostate cancer risk prediction models in Eastern Asian populations: current status, racial difference, and future directions.

Prostate cancer (PCa) risk calculators (RCs) with prostate-specific antigen (PSA) and other risk factors can greatly improve the accurate prediction of potential risk of PCa compared to PSA. The European Randomized Study of Screening for PCa Risk Calculator (ERSPC-RC) and the Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) are developed on the Western population. However, the Western RCs showed limited diagnostic efficacy in the Eastern Asian population, mainly due to racial differences between the two populations. We aimed to review the application of Western RCs and Eastern Asian RCs in Eastern Asian cohorts and to identify the characteristics and efficacy of these RCs.

Abstract TP193: Epidemiology of Intracerebral Hemorrhage in Qatar

Background: Intracerebral hemorrhage (ICH) accounts for 10 to 30 % of all strokes. However, the clinical outcome is worse than ischemic stroke with 50 % mortality rate at 30 days follow up. Qatar has a unique multi-cultural demography which may make the etiology and mechanism of ICH different from the west. There are no reports on the epidemiology of ICH from Qatar. Our study thus aims to evaluate the main risk factors and etiology based on the age and race of our current population. Method: Using our stroke database a retrospective analysis of prospectively collected data of patients with suspected stroke was undertaken . Our study sample included all ICH’s based on head CT imaging and clinical presentation. The etiology of ICH was based on age, risk factors and neurovascular imaging findings. Etiology was classified as: hypertension, CAA, vascular malformation, drug related and others (eg: vasculitis). Baseline characteristics of ICH population were assessed using univariate analysis (χ 2 test, ANOVA &amp; student t test). Multiple logistic regression analysis was performed to define predictors of ICH using SPSS 23 and P value of 0.05 was considered significant. Result: Out of 2525 strokes, 518 (20.5%) were ICH. Patients with ICH were younger with a mean age of 51.72±13.1 compared to ischemic strokes 56.12±13.38. (P value 0.68) Due to the population distribution of races, ICH was more common in the South Asians 201/518 (38.8%) followed by Filipino and Far East [FFE] 96/518 (18.5%), then Nepali 76/518 (14.7%) then Qatari and Arabic population 12% and 9.8% (P &lt; 0.001). The main risk factors for ICH were FFE and Nepali race followed by hypertension, obesity and diabetes. Hypertensive ICH remained the main mechanism across the different races. In the multiple logistic regression analysis, the main predictors of ICH were the FFE race (adjOR: 2.297, CI: 1.77-2.97, P-Value: 0.00) and hypertension (adj OR: 1.85 CI: 1.46-2.36, P-Value: 0.00, NIHSS (adjOR: 1.15 CI: 1.13-1.17, P-value: 0.00) and age (adjOR: 0.9, CI: 0.96-0.98, P-value: 0.00) Conclusion: The rate of ICH in Qatar is similar to the west. It is substantially low in the Qatari’s compared to the Far Eastern and South Asian population. Across all races the main risk factor and etiology remains uncontrolled hypertension.

The c.1085A>G Genetic Variant of CSF1R Gene Regulates Tumor Immunity by Altering the Proliferation, Polarization, and Function of Macrophages.

Purpose: Targeting tumor-associated macrophages with colony-stimulating factor 1 receptor (CSF-1R) inhibition reveals a strategy for cancer therapy. Here, we studied the impact of CSF1R germline genetic variant on CSF-1R signaling and the susceptibility to CSF-1R inhibitors.Experimental designs:CSF1R germline genetic variants were studied in 140 cancer patients. CSF-1R phosphorylation, endocytosis, and macrophage polarization were measured as the response to CSF-1 stimulation. Tumor-associated macrophages in surgical specimens and sensitivity to CSF-1R inhibitors were used to determine macrophage function.Results: A CSF1R c.1085A>G genetic variant causing the change of histidine to arginine in the domain of receptor dimerization was identified as a high allele frequency in Eastern Asian population. Cancer patients with this variant allele had less M2-like tumor-associated macrophages accompanied by low VEGF expression in tumor tissues. Importantly, CSF1R genetic variant was significantly associated with disease-free survival in colorectal, endometrial, and ovarian cancer. In terms of differentiation, macrophages with CSF1R c.1085A>G genetic variant displayed a refractory response to CSF-1 stimulation and macrophage survival was sensitive to CSF-1R inhibitors with IC50 of 0.1 to 1 nmol/L range. On contrast, CSF-1 induced a prominent phosphorylation and rapid endocytosis of CSF-1R, leading to an M2-like dominant polarization in macrophages with CSF1R c.1085 genotype A_A, in which CSF-1R inhibitors of PLX3397, BLZ945, and GW2580 inhibited macrophage survival with IC50 of 10 to 100 nmol/L range.Conclusions: The CSF1R c.1085A>G genetic variant regulates tumor immunity by altering the polarization and function of macrophages. This genetic variant confers the sensitivity to CSF-1R inhibitors, implying as a biomarker in targeting CSF-1R signaling for cancer treatment. Clin Cancer Res; 23(20); 6021-30. ©2017 AACR.

Determination of complete mitogenome sequence for Eastern Asian population of Cheilonereis cyclurus (Harrington, 1897) (Polychaeta: Nereididae)

Complete mitogenome sequence for eastern Asian population of Cheilonereis cyclurus (Polychaeta: Nereididae) was determined for the first time. The length of circular genome of C. cyclurus is 14,917 bp including 13 protein-coding genes, two rRNA genes, 22 tRNA genes, and a non-coding region of 383 bp. The gene order of C. cyclurus is identical to that of the following four nereidid species: Hediste diadroma, Namalycastis abiuma, Paraleonnates uschakovi, Tylorrhynchus heterochaetus. The phylogenetic position of C. cyclurus compared to 16 selected polychaetes was conducted and present species is closely related to the clade containing Perinereis nuntia, P. aibuhitensis, and Platynereis dumerilii with high bootstrap value.