Genetic assessment of hyperuricemia and gout in Asian, Native Hawaiian, and Pacific Islander subgroups of pregnant women: biospecimens repository cross-sectional study

Abstract Background Gout, an inflammatory condition, is characterized by the precipitation of monosodium urate crystals (MSU) in or around distal joints. The latter is caused by chronic hyperuricemia (HU)—high urate levels in the blood. Genetic variations in urate transporters play a significant role in determining urate levels within the human body, rendering some racial and ethnic groups more or less susceptible to developing either HU or gout. This study aims to estimate the frequencies of HU and gout risk alleles in Asian, Native Hawaiian, and Pacific Islander subgroups, using biorepository DNA samples. Methods The biospecimens repository at the University of Hawai’i provided DNA samples of consented post-partum women of Japanese, Filipino, Korean, Native Hawaiian, Samoan, and Marshallese descent. The DNA was previously extracted from maternal blood and genotyped at the Genomics and Bioinformatics Shared Resource, Cancer Center (Honolulu, HI). Nine urate genes: ABCG2, SLC2A9, SLC16A9, GCKR, SLC22A11, SLC22A12, LRR16A, PDZK1, and SLC17A1, were selected due to their significant association with HU and gout risk. Hardy–Weinberg Equilibrium (HWE) for genotype frequencies was assessed, using the Chi-Square test with p < 0.006 for statistical significance. Allele frequencies in our study were then compared to EUR from the 1000 Genomes Project Database Phase III, using Chi-square or Fisher's exact test, when appropriate. Bonferroni correction for multiple comparisons was used, with p < 0.006 for statistical significance. Results Our study involved 1059 post-partum women 18-year-old or older who self-reported their respective race and ethnicity, including Asian, Native Hawaiian, and Pacific Islander ancestry. The Asian subgroups included Japanese, Filipino, and Korean. The Pacific Islander subgroups included Marshallese and Samoan. None of the study participants had a history of gout. We excluded the PDZK1 gene from the final analysis due to its deviation from HWE (p < 0.006) across all the population subgroups, with eight loci remaining for cross-subgroup comparisons. Compared to EUR, the genetic polymorphism frequencies were significantly different-8/8 in Japanese, 6/8 in Korean, 6/8 in Filipino, 8/8 in Samoan, 6/8 in Native Hawaiian, and 6/8 in Marshallese. HU and gout risk alleles indices were 8, 6, 5, 5, 4, and 4 in Japanese, Filipino, Korean, Samoan, Marshallese, and Native Hawaiian, respectively. The percentage of cumulative risk alleles was 100% in both Japanese and Filipino, followed by 83.5% in Korean. Conclusions Compared to EUR, Asian subgroups, particularly Japanese, Filipino, and Korean, had the highest percentage of the cumulative uric acid risk alleles. These results could partly explain the increased risk of developing gout among some Asian ancestral subgroups compared to EUR.

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Genetic Assessment of Hyperuricemia and Gout in Asian, Native Hawaiian, and Pacific Islander Subgroups of Pregnant Women: Biospecimens Repository Cross-Sectional Study

10.21203/rs.3.rs-663266/v1 ◽

2021 ◽

Author(s):

Ali Alghubayshi ◽

Alison Edelman ◽

Khalifa Alrajeh ◽

Youssef Roman

Keyword(s):

Native Hawaiian ◽

Post Partum ◽

Statistical Significance ◽

Pacific Islander ◽

Cancer Center ◽

Fisher Exact Test ◽

Chi Square ◽

Risk Alleles ◽

Genotype Frequencies ◽

Increased Risk

Abstract BackgroundGout, an inflammatory condition, is characterized by the precipitation of monosodium urate crystals (MSU) in or around joints. The latter is caused by chronic hyperuricemia (HU) - high urate levels in the blood. Genetic variations in urate transporters play a significant role in determining urate levels within the human body, rendering some racial and ethnic groups more or less susceptible to developing HU or gout. This study aims to estimate the frequencies of HU and gout risk alleles in Asian, Native Hawaiian, and Pacific Islander subgroups, using biorepository DNA samples. MethodsThe biospecimens repository center at the University of Hawaii provided DNA samples of consented post-partum women of Japanese, Korean, Filipino, Native Hawaiian, Samoan, and Marshallese descent. The DNA was previously extracted from the cord blood and genotyped at the Genomics and Bioinformatics Shared Resource, Cancer Center (Honolulu, HI). Nine urate genes: ABCG2, SLC2A9, SLC16A9, GCKR, SLC22A11, SLC22A12, LRR16A, PDZK1, and SLC17A1, were selected due to their significant association with HU and gout risk. Hardy-Weinberg equilibrium for genotype frequencies was assessed, using the Chi-Square test with p<0.05 for statistical significance. Allele frequencies in our study were then compared to EUR from the 1000 Genomes Project Database, using the Chi-square or Fisher exact test as appropriate. Bonferroni correction for multiple comparisons was used, with p<0.006 for statistical significance. ResultsOur study involved 1095 post-partum women 18-year-old or older who self-reported their respective race and ethnicity, including Asian and Pacific Islander ancestry. Asian groups involved Korean, Japanese, and Filipino. Besides, the Pacific Islander group includes Native Hawaiian, Marshallese, and Samoan. None of the study participants had a history of gout. We excluded the PDZK1 gene from the final analysis due to its deviation from HWE (p<0.05) across all the populations. Compared to EUR, the genetic polymorphism frequencies were significantly different-8/8 in Japanese, 6/8 in Korean, 6/8 in Filipino,8/8 in Samoan, 6/8 in Hawaiian, and 6/8 in Marshallese. HU and gout risk alleles indices were 8, 5, 6, 5, 4, and 4 in Japanese, Korean, Filipinos, Samoans, Marshallese, and Hawaiians, respectively. The percentage of cumulative risk alleles was 100 percent in Japanese and Filipino followed by 83.5% in Korean. ConclusionsCompared to EUR, Asian subgroups, particularly Filipinos, Japanese, and Korean, had the highest risk of allele index. These results could partly explain that Asian people have an increased risk of developing HU or gout.

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Advance in the Management of Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation

Journal of Clinical Medicine ◽

10.3390/jcm8050728 ◽

2019 ◽

Vol 8 (5) ◽

pp. 728 ◽

Cited By ~ 40

Author(s):

Toshiaki Iba ◽

Jerrold Levy ◽

Aditya Raj ◽

Theodore Warkentin

Keyword(s):

Disseminated Intravascular Coagulation ◽

Statistical Significance ◽

Phase Iii ◽

Endothelial Glycocalyx ◽

Absolute Difference ◽

Sepsis Management ◽

Intravascular Coagulation ◽

Intravascular Thrombosis ◽

Increased Risk ◽

Recombinant Thrombomodulin

Coagulopathy commonly occurs in sepsis as a critical host response to infection that can progress to disseminated intravascular coagulation (DIC) with an increased mortality. Recent studies have further defined factors responsible for the thromboinflammatory response and intravascular thrombosis, including neutrophil extracellular traps, extracellular vesicles, damage-associated molecular patterns, and endothelial glycocalyx shedding. Diagnosing DIC facilitates sepsis management, and is associated with improved outcomes. Although the International Society on Thrombosis and Haemostasis (ISTH) has proposed criteria for diagnosing overt DIC, these criteria are not suitable for early detection. Accordingly, the ISTH DIC Scientific Standardization Committee has proposed a new category termed “sepsis-induced coagulopathy (SIC)” to facilitate earlier diagnosis of DIC and potentially more rapid interventions in these critically ill patients. Therapy of SIC includes both treatment of the underlying infection and correcting the coagulopathy, with most therapeutic approaches focusing on anticoagulant therapy. Recently, a phase III trial of recombinant thrombomodulin was performed in coagulopathic patients. Although the 28-day mortality was improved by 2.6% (absolute difference), it did not reach statistical significance. However, in patients who met entry criteria for SIC at baseline, the mortality difference was approximately 5% without increased risk of bleeding. In this review, we discuss current advances in managing SIC and DIC.

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Predicting men at high risk for PSA failure after salvage radiotherapy for rising PSA following prostatectomy

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4570 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4570-4570

Author(s):

O. K. MacDonald ◽

A. V. D’Amico ◽

N. Sadetsky ◽

D. C. Shrieve ◽

A. W. Bakst ◽

...

Keyword(s):

Seminal Vesicle ◽

Multivariable Analysis ◽

Salvage Radiotherapy ◽

Phase Iii ◽

Chi Square ◽

Seminal Vesicle Invasion ◽

Increased Risk ◽

Psa Failure ◽

Psa Recurrence ◽

Cancer Of The Prostate

4570 Background: Single and multi-institutional reports have published results indicating 5-year PSA response rates of 30 to 50% in men following salvage radiotherapy (RT) for rising PSA after radical prostatectomy (RP) depending upon the patient and disease factors. We analyzed a longitudinal observational database of men who received salvage RT following RP for their prostate cancer to evaluate for predictors of PSA failure despite salvage RT. Methods: Data from the Cancer of the Prostate Strategic Urologic Research Endeavor database (CaPSURE) identified 5,336 men with RP between 1989 and 2004; 200 underwent salvage RT ≥6 months after RP. PSA recurrence following salvage RT was defined as a PSA >0.2 ng/mL. A measure of the association between clinical and pathologic characteristics in men experiencing PSA failure following salvage RT was examined using a chi-square metric. Univariable and multivariable analyses of predictors for PSA recurrence using a Cox proportional hazard regression model were performed. Results: After a mean follow-up of 18 months (range 1 to 131 months), 121 (62%) men experienced PSA recurrence at a mean 13.7 months after salvage RT. Significant associations between time to PSA recurrence after salvage RT were found with the clinical risk group (p < .01), clinical T category (p < .01), race/ethnicity (p = .04), extraprostatic extension (p < .01), seminal vesicle invasion (p < .01), and pre-salvage RT PSA level (p < .01). The pre-salvage RT PSA level (p = .003) and seminal vesicle invasion (p = .02) remained significantly associated with time to PSA recurrence on multivariable analysis. Conclusions: The pre-salvage RT PSA level and the presence of seminal vesicle invasion were significantly associated with time to PSA recurrence following salvage RT within the CaPSURE database. Men with these risk factors are at increased risk for PSA recurrence despite salvage RT suggesting that these men would be ideal candidates for entry onto phase III studies comparing salvage RT plus systemic therapy with salvage RT alone at the time of post-operative PSA failure. [Table: see text]

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Presence of variant histology (VarHst) in transurethral resection of bladder tumor (TURBT) biopsies and its prognostic significance on pathologic complete response (pCR) rates to neoadjuvant chemotherapy (neo-CTx).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.295 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 295-295

Author(s):

Jose Alexandre Pedrosa ◽

Kevin Rice ◽

Derek E. Thomas ◽

Paul Johnston ◽

Marietta L. Moore ◽

...

Keyword(s):

Multinomial Logistic Regression ◽

Statistical Significance ◽

Clinical Stage ◽

Pathologic Complete Response ◽

Prognostic Significance ◽

Phase Iii ◽

Cancer Center ◽

Clinical Value ◽

Curative Intent ◽

Clinical Databases

295 Background: Randomized phase III clinical trial data (S8710) supports an overall survival (OS) advantage with neo-CTx for muscle-invasive urothelial carcinoma (miUC) patients (pts) prior to cystectomy. Recent S8710 subset analyses have demonstrated an OS for pts with both pure UC and VarHst. pCR to neo-CTx has been suggested as a surrogate endpoint for OS. The relationship between VarHist in TURBT specimens and pCR rates is uncertain. Methods: A retrospective review of the Indiana University Simon Cancer Center urology and medical oncology clinical databases was performed spanning the years 1991 – 2012. Subjects with miUC, pathology reports available for both TURBT and cystectomy procedures, and confirmed receipt of neo-CTx with regimen details were included in this analysis. Pts with clinically positive lymph nodes (LN+) were included provided they underwent cystectomy with curative intent and distant metastases were not present. Associations between pCR and pt baseline age, gender, race, clinical stage (T2N0 vs. T3/T4/N+), chemotherapy regimen received (cisplatin combination therapy (CisCTx) vs. non-cisplatin based), and presence of VarHst on TURBT sample were tested by multinomial logistic regression analysis with statistical significance set at p<0.05. Results: 72 miUC pts satisfying the inclusion criteria were identified. Cohort demographics included: age (median) – 59 yrs, 76% male, 93% Caucasian, 63% T2N0, 32% LN+, 81% CisCTx neo-CTx regimen, 42% VarHst on TURBT, pCR for entire cohort 18%. The presence of VarHst on TURBT sample was not associated with decreased rates of pCR (6/30 vs. 7/42) p=0.610. A trend toward significance with age over 59 was also observed. Conclusions: The presence of VarHst in TURBT specimen is not associated with decreased rates of pCR at cystectomy in miUC pts treated with neo-CTx. Further characterization of the amount of VarHst and reproducibility of its recognition in TURBT samples is warranted to determine its ultimate clinical value.

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Variations in Nuss Procedure Operative Techniques and Complications: A Retrospective Review

European Journal of Pediatric Surgery ◽

10.1055/s-0041-1735164 ◽

2021 ◽

Author(s):

Centura R. Anbarasu ◽

Steven C. Mehl ◽

Raphael C. Sun ◽

Jorge I. Portuondo ◽

Andres F. Espinoza ◽

...

Keyword(s):

Retrospective Review ◽

Pectus Excavatum ◽

Statistical Significance ◽

Intercostal Nerve ◽

Nuss Procedure ◽

Operative Techniques ◽

Chi Square ◽

Patient Demographics ◽

Haller Index ◽

Increased Risk

Abstract Introduction The Nuss procedure is the most common and preferred operative correction of pectus excavatum. Surgeon preference and patient factors can result in variations in Nuss procedure technique. We hypothesize that certain techniques are associated with increased risk of complications. Materials and Methods We performed a single-center retrospective review of Nuss operations from 2016 to 2020. Variations in intraoperative techniques included sternal elevator (SE) use, number of bars placed, and usage of bilateral stabilizing sutures. Patient demographics, intraoperative data, and postoperative outcomes were reported as median with interquartile ranges or percentages. Statistical significance (p < 0.05) was determined with Wilcoxon's rank-sum and chi-square tests. Multivariate analysis was performed to control for introduction of intercostal nerve cryoablation and surgeon volume, and reported as odds ratio with 95% confidence interval. Results Two hundred and sixty-five patients were identified. Patients repaired with two bars were older with a larger Haller index (HI). Patient demographics were not significantly different for SE or stabilizing suture use. Placement of two bars was associated with significantly increased risk of readmission. Similarly, SE use was associated with increased risk of pleural effusion and readmission. Finally, the use of bilateral stabilizing sutures resulted in less frequent slipped bars without statistical significance. Conclusion Older patients with a larger HI were more likely to need two bars placed to repair pectus excavatum. Placement of multiple bars and SE use are associated with significantly higher odds of certain complications.

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Risk of Bleeding with Ibrutinib in Patients with B-Cell Malignancies: An Updated Meta-Analysis of Phase III Randomized Controlled Trials

Blood ◽

10.1182/blood-2018-99-120161 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5553-5553

Author(s):

Somedeb Ball ◽

Abhishek Maiti ◽

Meily Arevalo ◽

Avash Das ◽

Wasawat Vutthikraivit ◽

...

Keyword(s):

B Cell ◽

Meta Analysis ◽

Statistical Significance ◽

Final Analysis ◽

Phase Iii ◽

Controlled Trials ◽

B Cell Malignancies ◽

Major Hemorrhage ◽

Randomized Controlled ◽

Increased Risk

Abstract Introduction: Ibrutinib is an oral Bruton's tyrosine kinase (BTK) inhibitor which has transformed the management of several B-cell malignancies. Ibrutinib has been associated with an increased incidence of bleeding in retrospective studies. This phenomenon has been explained by potential effects of ibrutinib on different aspects of platelet function, including adhesion and aggregation, mainly through modification of BTK signaling pathways in platelets. A previous meta-analysis (Caron et al.) found a significant increase in overall bleeding in ibrutinib recipients. We conducted an updated systematic review and meta-analysis of all phase III randomized controlled trials (RCT) available till date to determine the relative risk of overall bleeding associated with ibrutinib use, relative risk of major hemorrhage, and to evaluate if the risk estimate has changed with emergence of new data since prior reports. Methods: We performed a systematic search of Embase, PubMed, Web of Science, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov with appropriate keywords through 07/10/18, to find all RCTs comparing ibrutinib with other agents or placebo in patients with B-cell malignancies and also reporting bleeding as a treatment-emergent adverse event. The search strategy, study selection, data extraction, and analysis were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. We pooled the point estimates using random effects model of the generic inverse-variance method described by Der Simonian and Laird. Statistical analyses were performed using the Stata/SE 15.1 (StataCorp LP, College Station, TX, USA). Results: A total of 6 phase III RCTs randomizing 1811 patients (pt; 935 on ibrutinib arms and 876 in the control arms) were included in the final analysis. Four trials were conducted in pts with CLL, one in pts with Waldenstrom macroglobulinemia and the other one in pts with mantle cell lymphoma. Characteristics of these trials are shown in Table 1. In 4 RCTs ibrutinib was compared with an active agent (i.e., ofatumumab, chlorambucil, temsirolimus, and rituximab) and in the other two trials, it was compared with placebo. Ibrutinib was administered as a 1st-line therapy in the RESONATE-2 trial and both as 1st line and in refractory cases in the iNNOVATE trial. The median duration of treatment across studies with ibrutinib was 17.7 months (range 9.4-38.7 months). Major hemorrhage was usually defined as grade 3-5 bleeding or central nervous system bleeding of any grade across trials. The pooled risk ratio (RR) for total number of bleeding events was 2.43 [95%CI: 1.47-4.00, p<0.001, I2=82.5%, figure 1A] in patients on ibrutinib across all B-cell malignancies, as compared to their counterparts in the control arms. The pooled RR for incidence of major hemorrhage in the ibrutinib arm was 1.71 [95%CI: 0.99-2.95, p=0.056, I2=0.0%, figure 1B], showing trend towards statistical significance as compared to control. In subgroup analysis of trials (n=4) in pts with CLL only, ibrutinib was again associated with a significantly increased risk of overall bleeding [pooled RR 3.23, 95%CI: 1.72-6.06, p<0.001, I2=72.7%, figure 2A], although the relative increase in risk was not significant [pooled RR 1.74, 95%CI: 0.83-3.67, p=0.142, I2=0.0%, figure 2B] in the patients on ibrutinib when number of major hemorrhages were compared in both groups. No publication bias was observed across all the studies included in final analysis. Conclusion: In this meta-analysis, ibrutinib was associated with a significantly increased risk of overall bleeding in patients with B-cell malignancies, and incidence of major hemorrhages in ibrutinib arm showed trend towards statistical significance. Knowledge about increased risk of this adverse event should help clinicians to contribute to alleviation of overall morbidity and mortality in patients. Disclosures Maiti: Celgene Corporation: Other: Research funding to the institution.

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128 Pregnancy and calving rates of beef cows comparing the sex-selected semen to conventional semen using timed artificial insemination

Journal of Animal Science ◽

10.1093/jas/skz397.002 ◽

2020 ◽

Vol 98 (Supplement_2) ◽

pp. 1-1

Author(s):

Jennifer McMurray ◽

Andrea N DeCarlo ◽

Nathan Long ◽

Scott Pratt

Keyword(s):

Artificial Insemination ◽

Post Partum ◽

Statistical Significance ◽

Fixed Time ◽

Beef Cows ◽

Pregnancy Rates ◽

Chi Square ◽

Estrous Synchronization ◽

Beef Cow ◽

Sexed Semen

Abstract A study was conducted over three years to determine if differences in pregnancy rates existed between the use of commercially available sex-selected (SEXED) or conventional semen (STD) coupled to fixed-time artificial insemination (TAI). A total of 240 (2016: n = 80; 2017: n = 95; 2018: n = 65) primi- or multiparous Angus or Angus-cross cows being at 45 days post-partum or greater were blocked by weight and BCS and assigned to be inseminated using SEXED semen or STD semen. Artificial insemination was performed by the same AI technicians (n = 3) across all years. All cows were subjected to estrous synchronization and insemination using the SEXED semen or STD semen with TAI between 63 and 66 h post-CIDR removal. Fourteen days post-TAI all cows were exposed to bulls for natural service. Cows were subjected to transrectal ultrasonography at day 30 and day 45 post-TAI to determine pregnancy rates and calving dates in the subsequent calving seasons were recorded to determine calving rates to TAI. Pregnancy rates were compared using a Chi-square test of two proportions. All statistical calculations were performed using JMP software and statistical significance was based on p-values less than 0.05. Pregnancy rates at day 30 and day 45 were 39.67% and 48.76% for SEXED and 47.90% and 54.62% for STD, respectively (P > 0.05). The percentage of calves born to TAI pregnancies for sex-selected semen and conventional semen were 22.31% and 40.34%, respectively (P < 0.05). These data indicate that the use of sex-selected semen can give similar pregnancy results to conventional semen in beef cow operations using TAI at day 30 of gestation; however, there was a reduction in the number of offspring to TAI comparing calving dates to animals pregnant at day 30.

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Abstract 15463: Pre-procedural Inr, Bleeding, and Mortality in the Catheterization Lab: Does INR Still Matter in the Radial First Era?

Circulation ◽

10.1161/circ.142.suppl_3.15463 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Shantum Misra ◽

Bruce W Andrus ◽

James T Devries

Keyword(s):

Hospital Mortality ◽

Statistical Significance ◽

Coronary Intervention ◽

Mitigation Strategies ◽

Categorical Variables ◽

Continuous Variables ◽

Access Site ◽

Chi Square ◽

Increased Risk ◽

Chi Square Analysis

Background: Warfarin anticoagulation presents a common barrier to undergoing cardiac catheterization procedures. Using radial access and other bleeding mitigation strategies, it is not known if elevated INR truly portends an increased risk of adverse events. We sought to understand the relationship between in hospital mortality and bleeding with INR in patients undergoing coronary interventional catheterization procedures. Methods: The prospectively-collected Dartmouth Dynamic Registry was queried for all patients who underwent catheterization with coronary intervention from 2014 to 2018. Of the 5015 patients identified, 2120 patients had a recorded INR value within 24 hours of the procedure. Demographics, procedural variables, and in hospital outcomes were collected. Patients were divided into two groups: INR &lt1.8 and INR &gt1.8. Incidence of bleeding (access site hematoma &gt5cm, post procedure blood transfusion) as well as in-hospital mortality were queried for each group. Stata was used to determine statistical significance, using chi-square analysis for categorical variables and standard t-test for continuous variables. Results: Of the 2120 patients with INR values, 1968 patients were identified with INR &lt1.8 (median INR 1.1; range 0.7-1.7) and 152 patients with INR &gt1.8 (median INR 2.2; range 1.8-11.1). Patients with elevated INRs had higher acuity (urgent or emergent cases) and were older. Other baseline and procedural characteristics were similar. Outcomes between those with elevated INR and those with lower INR values were similar, including access site injury, hematoma, and need for transfusion (Table I). Overall mortality did not differ between the two groups. Conclusion: When compared to patients with INR &lt1.8, patients with INR &gt1.8 are more likely to undergo coronary intervention on an urgent or emergent basis. Despite this, there is no difference in bleeding, need for transfusion, or overall in-hospital mortality.

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Diagnostic Lobectomy for Bethesda III Thyroid Nodules: Pathological Outcomes and Risk Factors for Malignancy

Annals of Otology Rhinology & Laryngology ◽

10.1177/0003489421993976 ◽

2021 ◽

pp. 000348942199397

Author(s):

Benjamin K. Walters ◽

Samuel L. Garrett ◽

James K. Aden ◽

Grant M. Williams ◽

Samantha L. Butler-Garcia ◽

...

Keyword(s):

Risk Factors ◽

Thyroid Nodules ◽

Medical Center ◽

Statistical Significance ◽

Retrospective Chart Review ◽

Needle Aspiration ◽

Chi Square ◽

Increased Risk ◽

Risk Of Malignancy ◽

History Of

Objective: An indeterminate thyroid nodule fine-needle aspiration (FNA) presents a unique dilemma. We evaluated our institution’s experience with Bethesda III thyroid nodules, including the risk of malignancy (ROM) of these nodules removed for diagnostic lobectomy and radiologic and clinical risk factors for malignancy. Study design: Retrospective chart review. Setting: San Antonio Military Medical Center (SAMMC; 483 bed Military Treatment Facility and Level 1 Trauma Center). Methods: We identified all patients with a Bethesda III thyroid FNA at our institution from 2010 to 2018 and determined which nodules were removed. The final histological diagnosis was recorded. Whether or not age, gender, body mass index (BMI), race, nodule size, margin regularity, rate of nodule growth, vascularity, internal calcifications, family history of thyroid cancer, personal history of radiation, and history of repeated AUS/FLUS on FNA had a significant impact on malignancy risk was evaluated with chi square and rank sum Wilcoxon tests. Results: 492 patients had 1 or more AUS result. 52% (258/492) underwent repeat FNA. This resulted in Bethesda II or III in 90% (232/258). In 10% (26/258), the repeat FNA resulted in a higher Bethesda grade. 183 lobectomies were performed on the side containing an AUS nodule. The malignancy percentage was 38.3% (70/183). Age less than 30 was the only variable showing statistical significance for increased risk of malignancy ( P = .04). Conclusion: The ROM of nodules characterized as AUS/FLUS on FNA may be higher than expected. Age may be a better predictor of malignancy than repeat FNA.

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Evaluation of the Relationship Between Cytochrome P450 Polymorphisms and T2DM Risk

10.21203/rs.3.rs-74188/v1 ◽

2020 ◽

Author(s):

QingBin Zhao ◽

Huiyi Wei ◽

Zhiying Li ◽

Haoyang Wei

Keyword(s):

Statistical Significance ◽

Nucleotide Polymorphisms ◽

Chi Square ◽

Single Nucleotide ◽

Gender Stratification ◽

Genotype Frequencies ◽

Chi Square Test ◽

The Relationship ◽

Control Study

Abstract Background: Recent studies have identified some genetic polymorphisms of CYP2C8 and CYP2D6 related to disease susceptibility. However, it has not been reported whether polymorphisms in CYP2C8 and CYP2D6 are associated with the risk of type 2 diabetes mellitus (T2DM). We designed a case-control study to evaluate the relationship between those CYP polymorphisms and T2DM risk. Methods: Four single nucleotide polymorphisms (SNPs) of CYP2C8 and CYP2D6 were genotyped from 512 patients and 515 healthy controls using Agena MassARRAY. The chi-square test was used to compare the differences in allele and genotype frequencies between the two groups. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression analysis to evaluate the relationship between polymorphism and T2DM risk. Results: The results found that the rs1065852 in CYP2D6 was correlated with the T2DM risk in overall (A vs. G: OR = 1.22, 95% CI: 1.03–1.45, P = 0.024; AA vs.GG: OR = 1.46, 95% CI: 1.04–2.06, P = 0.031; AA-AG vs. GG: OR = 1.36, 95% CI: 1.04–1.79, P = 0.026; additive: OR = 1.21, 95% CI: 1.02–1.44, P = 0.027). Gender stratification analysis results demonstrated that the rs1065852 in CYP2D6 was related with an increased the risk of T2DM in male and age < 59 years old. However, no statistical significance relation was found between CYP2C8 SNPs and T2DM risk. Conclusions: This study revealed that CYP2D6 (rs1065852) could be potential genetic markers of susceptibility to T2DM. Further studies are required to confirm our findings.

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