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Article ; Online: Ketamine dose reporting and dose responsiveness for chronic pain.

Cohen, Steven P / Khunsriraksakul, Chachrit / Cohen, Seffrah J / Moon, Jee Youn

2023 Volume 24, Issue 10, Page(s) 1211–1212

MeSH term(s)	Humans ; Ketamine/therapeutic use ; Chronic Pain/drug therapy ; Anesthetics, Dissociative ; Analgesics/therapeutic use
Chemical Substances	Ketamine (690G0D6V8H) ; Anesthetics, Dissociative ; Analgesics
Language	English
Publishing date	2023-05-11
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Comment
ZDB-ID	2015903-1
ISSN	1526-4637 ; 1526-2375
ISSN (online)	1526-4637
ISSN	1526-2375
DOI	10.1093/pm/pnad059
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Article ; Online: Construction and Application of Polygenic Risk Scores in Autoimmune Diseases.

Khunsriraksakul, Chachrit / Markus, Havell / Olsen, Nancy J / Carrel, Laura / Jiang, Bibo / Liu, Dajiang J

Frontiers in immunology

2022 Volume 13, Page(s) 889296

Abstract: Genome-wide association studies (GWAS) have identified hundreds of genetic variants associated with autoimmune diseases and provided unique mechanistic insights and informed novel treatments. These individual genetic variants on their own typically ... ...

Abstract	Genome-wide association studies (GWAS) have identified hundreds of genetic variants associated with autoimmune diseases and provided unique mechanistic insights and informed novel treatments. These individual genetic variants on their own typically confer a small effect of disease risk with limited predictive power; however, when aggregated (e.g.,
MeSH term(s)	Autoimmune Diseases/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study/methods ; Humans ; Lupus Erythematosus, Systemic/diagnosis ; Lupus Erythematosus, Systemic/genetics ; Risk Factors
Language	English
Publishing date	2022-06-27
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.889296
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Article ; Online: Real-World Data: Applications and Relevance to Cancer Clinical Trials.

Gross, Andrew J / Pisano, Courtney E / Khunsriraksakul, Chachrit / Spratt, Daniel E / Park, Henry S / Sun, Yilun / Wang, Ming / Zaorsky, Nicholas G

Seminars in radiation oncology

2023 Volume 33, Issue 4, Page(s) 374–385

Abstract: Randomized controlled trials (RCTs) are the gold standard for comparative-effectiveness research (CER). Since the 1980s, there has been a rise in the creation and utilization of large national cancer databases to provide readily accessible "real-world ... ...

Abstract	Randomized controlled trials (RCTs) are the gold standard for comparative-effectiveness research (CER). Since the 1980s, there has been a rise in the creation and utilization of large national cancer databases to provide readily accessible "real-world data" (RWD). This review article discusses the role of RCTs in oncology, and the role of RWD from the national cancer database in CER. RCTs remain the preferred study type for CER because they minimize confounding and bias. RCTs have challenges to conduct, including extensive time and resources, but these factors do not impact the internal validity of the result. Generalizability and external validity are potential limitations of RCTs. RWD is ideal for studying cancer epidemiology, patterns of care, disparities in care delivery, quality-of-care evaluation, and applicability of RCT data in specific populations excluded from RCTs. However, retrospective databases with RWD have limitations in CER due to unmeasured confounders and are often suboptimal in identifying causal treatment effects.
MeSH term(s)	Humans ; Comparative Effectiveness Research ; Databases, Factual ; Medical Oncology ; Neoplasms/epidemiology ; Neoplasms/therapy ; Research Design ; Clinical Trials as Topic
Language	English
Publishing date	2023-09-06
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1146999-7
ISSN	1532-9461 ; 1053-4296
ISSN (online)	1532-9461
ISSN	1053-4296
DOI	10.1016/j.semradonc.2023.06.003
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Article ; Online: Factors associated with pregnancy termination in women of childbearing age in 36 low-and middle-income countries.

Ba, Djibril M / Zhang, Yue / Pasha-Razzak, Omrana / Khunsriraksakul, Chachrit / Maiga, Mamoudou / Chinchilli, Vernon M / Ssentongo, Paddy

PLOS global public health

2023 Volume 3, Issue 2, Page(s) e0001509

Abstract: Lack of access to safe, affordable, timely and adequate pregnancy termination care, and the stigma associated with abortion in low-middle income countries (LMICs), pose a serious risk to women's physical and mental well-being throughout the lifespan. ... ...

Abstract	Lack of access to safe, affordable, timely and adequate pregnancy termination care, and the stigma associated with abortion in low-middle income countries (LMICs), pose a serious risk to women's physical and mental well-being throughout the lifespan. Factors associated with pregnancy termination and their heterogeneity across countries in LMICs previously have not been thoroughly investigated. We aim to determine the relative significance of factors associated with pregnancy termination in LMICs and its variation across countries. Analysis of cross-sectional nationally representative household surveys carried out in 36 LMICs from 2010 through 2018. The weighted population-based sample consisted of 1,236,330 women of childbearing aged 15-49 years from the Demographic and Health Surveys. The outcome of interest was self-report of having ever had a pregnancy terminated. We used multivariable logistic regression models to identify factors associated with pregnancy termination. The average pooled weighted prevalence of pregnancy termination in the present study was 13.3% (95% CI: 13.2%-13.4%), ranging from a low of 7.8 (95% CI: 7.2, 8.4%) in Namibia to 33.4% (95% CI: 32.0, 34.7%) in Pakistan. Being married showed the strongest association with pregnancy termination (adjusted OR, 2.94; 95% CI, 2.84-3.05; P < 0.001) compared to unmarried women. Women who had more than four children had higher odds of pregnancy termination (adjusted OR, 2.45; 95% CI, 2.33-2.56; P < 0.001). Moreover, increased age and having primary and secondary levels of education were associated with higher odds of pregnancy termination compared to no education. In this study, married women, having one or more living children, those of older age, and those with at least primary level of education were associated with pregnancy termination in these 36 LMICs. The findings highlighted the need of targeted public health intervention to reduce unintended pregnancies and unsafe abortions.
Language	English
Publishing date	2023-02-28
Publishing country	United States
Document type	Journal Article
ISSN	2767-3375
ISSN (online)	2767-3375
DOI	10.1371/journal.pgph.0001509
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Article ; Online: Analysis of anemia and iron supplementation among glioblastoma patients reveals sex-biased association between anemia and survival.

Shenoy, Ganesh / Slagle-Webb, Becky / Khunsriraksakul, Chachrit / Pandya Shesh, Bhavyata / Luo, Jingqin / Khristov, Vladimir / Smith, Nataliya / Mansouri, Alireza / Zacharia, Brad E / Holder, Sheldon / Lathia, Justin D / Barnholtz-Sloan, Jill S / Connor, James R

Scientific reports

2024 Volume 14, Issue 1, Page(s) 2389

Abstract: The association between anemia and outcomes in glioblastoma patients is unclear. We analyzed data from 1346 histologically confirmed adult glioblastoma patients in the TriNetX Research Network. Median hemoglobin and hematocrit levels were quantified for ... ...

Abstract	The association between anemia and outcomes in glioblastoma patients is unclear. We analyzed data from 1346 histologically confirmed adult glioblastoma patients in the TriNetX Research Network. Median hemoglobin and hematocrit levels were quantified for 6 months following diagnosis and used to classify patients as anemic or non-anemic. Associations of anemia and iron supplementation of anemic patients with median overall survival (median-OS) were then studied. Among 1346 glioblastoma patients, 35.9% of male and 40.5% of female patients were classified as anemic using hemoglobin-based WHO guidelines. Among males, anemia was associated with reduced median-OS compared to matched non-anemic males using hemoglobin (HR 1.24; 95% CI 1.00-1.53) or hematocrit-based cutoffs (HR 1.28; 95% CI 1.03-1.59). Among females, anemia was not associated with median-OS using hemoglobin (HR 1.00; 95% CI 0.78-1.27) or hematocrit-based cutoffs (HR: 1.10; 95% CI 0.85-1.41). Iron supplementation of anemic females trended toward increased median-OS (HR 0.61; 95% CI 0.32-1.19) although failing to reach statistical significance whereas no significant association was found in anemic males (HR 0.85; 95% CI 0.41-1.75). Functional transferrin-binding assays confirmed sexually dimorphic binding in resected patient samples indicating underlying differences in iron biology. Anemia among glioblastoma patients exhibits a sex-specific association with survival.
MeSH term(s)	Adult ; Humans ; Male ; Female ; Iron ; Glioblastoma/complications ; Anemia/complications ; Hemoglobins/metabolism ; Dietary Supplements
Chemical Substances	Iron (E1UOL152H7) ; Hemoglobins
Language	English
Publishing date	2024-01-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-52492-8
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Article ; Online: Association of Spinal Cord Stimulator Implantation With Persistent Opioid Use in Patients With Postlaminectomy Syndrome.

Vu, To-Nhu / Khunsriraksakul, Chachrit / Vorobeychik, Yakov / Liu, Alison / Sauteraud, Renan / Shenoy, Ganesh / Liu, Dajiang J / Cohen, Steven P

JAMA network open

2022 Volume 5, Issue 1, Page(s) e2145876

Abstract: Importance: The results of studies evaluating spinal cord stimulation (SCS) for postlaminectomy syndrome (PLS) have yielded mixed results. This has led to an increased emphasis on objective outcome measures such as opioid prescribing.: Objective: To ... ...

Abstract	Importance: The results of studies evaluating spinal cord stimulation (SCS) for postlaminectomy syndrome (PLS) have yielded mixed results. This has led to an increased emphasis on objective outcome measures such as opioid prescribing. Objective: To determine the association between SCS and long-term opioid therapy (LOT) for PLS. Design, setting, and participants: In this cohort study, adults with PLS were identified using the TriNetx Diamond Network and separated based on whether they underwent SCS. Patients were stratified according to baseline opioid use (opioid-naive or receiving LOT) and subsequent opioid therapy over the 12-month period ranging from 3 to 15 months post-SCS implantation or post-PLS index date. Statistical analysis was performed from June to December 2021. Exposure: SCS. Main outcomes and measures: The main outcome was cessation of opioid use among patients receiving LOT or abstinence from opioids among opioid-naive patients. Opioid-naive patients were defined as those receiving at most 2 opioid prescriptions per year, and patients on LOT were those receiving at least 6 opioid prescriptions per year. Results: Among 552 937 eligible patients treated between December 2015 and May 2021, 26 179 with PLS received an SCS implant. The median (IQR) patient age was 60 (51-69) years; 305 802 patients (55.3%) were female. Among those reporting racial identify (37.0% [204 758 patients]), 9.3% (18 971 patients) were African American, 0.3% (648 patients) were Asian, and 90.4% (185 139 patients) were White. Compared with those who did not receive an SCS, individuals who received an SCS were more likely to be using opioids preimplantation (mean [SD] prescriptions: 4.3 [8.5] vs 4.1 [9.3]; P < .001) but less likely to be using opioids after SCS implantation (mean [SD] prescriptions: 3.8 [8.2] vs 4.0 [9.4]; P = .006). In the 12-month study period, similar proportions in the SCS and no-SCS groups receiving baseline LOT remained on LOT (70.3% [n = 74 585] vs 69.2% [n = 3882], respectively; P = .10). In opioid-naive patients, SCS was associated with a small decreased likelihood of patients subsequently receiving LOT (7.6% vs 7.0%; difference, -0.6% [95% CI, -1.0% to -0.2%]; P = .003). In multivariable analysis, SCS was associated with an increased likelihood of not being on opioids in both opioid-naive (adjusted odds ratio [OR], 0.90 [95% CI, 0.85-0.96]; P < .001) and LOT patients (adjusted OR, 0.93 [95% CI, 0.88-0.99]; P = .02). White patients were significantly more likely to be diagnosed with PLS (ie, underwent surgery) (90.4% vs 85.2%; difference, 5.2% [95% CI, 5.1%-5.4%]; P < .001) and receive an SCS (93.7% vs 90.3%; difference, 3.4% [95% CI, 2.9% to 4.0%]; P < .001) than patients of other racial identities. Conclusions and relevance: These findings suggest that under real-life conditions, SCS was associated with small, clinically questionable associations with opioid discontinuation and not starting opioids in the context of PLS.
MeSH term(s)	Aged ; Analgesics, Opioid/therapeutic use ; Drug Prescriptions/statistics & numerical data ; Failed Back Surgery Syndrome/therapy ; Female ; Humans ; Laminectomy/adverse effects ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Postoperative Period ; Practice Patterns, Physicians'/statistics & numerical data ; Prosthesis Implantation ; Spinal Cord Stimulation/statistics & numerical data
Chemical Substances	Analgesics, Opioid
Language	English
Publishing date	2022-01-04
Publishing country	United States
Document type	Evaluation Study ; Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2574-3805
ISSN (online)	2574-3805
DOI	10.1001/jamanetworkopen.2021.45876
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Article ; Online: Future trends in incidence and long-term survival of metastatic cancer in the United States.

Hudock, Nicholas L / Mani, Kyle / Khunsriraksakul, Chachrit / Walter, Vonn / Nekhlyudov, Larissa / Wang, Ming / Lehrer, Eric J / Hudock, Maria R / Liu, Dajiang J / Spratt, Daniel E / Zaorsky, Nicholas G

Communications medicine

2023 Volume 3, Issue 1, Page(s) 76

Abstract: Background: Previous studies have demonstrated epidemiological trends in individual metastatic cancer subtypes; however, research forecasting long-term incidence trends and projected survivorship of metastatic cancers is lacking. We assess the burden of ...

Abstract	Background: Previous studies have demonstrated epidemiological trends in individual metastatic cancer subtypes; however, research forecasting long-term incidence trends and projected survivorship of metastatic cancers is lacking. We assess the burden of metastatic cancer to 2040 by (1) characterizing past, current, and forecasted incidence trends, and (2) estimating odds of long-term (5-year) survivorship. Methods: This retrospective, serial cross-sectional, population-based study used registry data from the Surveillance, Epidemiology, and End Results (SEER 9) database. Average annual percentage change (AAPC) was calculated to describe cancer incidence trends from 1988 to 2018. Autoregressive integrating moving average (ARIMA) models were used to forecast the distribution of primary metastatic cancer and metastatic cancer to specific sites from 2019 to 2040 and JoinPoint models were fitted to estimate mean projected annual percentage change (APC). Results: The average annual percent change (AAPC) in incidence of metastatic cancer decreased by 0.80 per 100,000 individuals (1988-2018) and we forecast an APC decrease by 0.70 per 100,000 individuals (2018-2040). Analyses predict a decrease in metastases to liver (APC = -3.40, 95% CI [-3.50, -3.30]), lung (APC (2019-2030) = -1.90, 95% CI [-2.90, -1.00]); (2030-2040) = -3.70, 95% CI [-4.60, -2.80]), bone (APC = -4.00, 95% CI [-4.30, -3.70]), and brain (APC = -2.30, 95% CI [-2.60, -2.00]). By 2040, patients with metastatic cancer are predicted to have 46.7% greater odds of long-term survivorship, driven by increasing plurality of patients with more indolent forms of metastatic disease. Conclusions: By 2040, the distribution of metastatic cancer patients is predicted to shift in predominance from invariably fatal to indolent cancers subtypes. Continued research on metastatic cancers is important to guide health policy and clinical intervention efforts, and direct allocations of healthcare resources.
Language	English
Publishing date	2023-05-27
Publishing country	England
Document type	Journal Article
ISSN	2730-664X
ISSN (online)	2730-664X
DOI	10.1038/s43856-023-00304-x
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Article ; Online: Iron inhibits glioblastoma cell migration and polarization.

Shenoy, Ganesh / Kheirabadi, Sina / Ataie, Zaman / Sahu, Aurosman Pappus / Palsa, Kondaiah / Wade, Quinn / Khunsriraksakul, Chachrit / Khristov, Vladimir / Slagle-Webb, Becky / Lathia, Justin D / Wang, Hong-Gang / Sheikhi, Amir / Connor, James R

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2023 Volume 37, Issue 12, Page(s) e23307

Abstract: Glioblastoma is one of the deadliest malignancies facing modern oncology today. The ability of glioblastoma cells to diffusely spread into neighboring healthy brain makes complete surgical resection nearly impossible and contributes to the recurrent ... ...

Abstract	Glioblastoma is one of the deadliest malignancies facing modern oncology today. The ability of glioblastoma cells to diffusely spread into neighboring healthy brain makes complete surgical resection nearly impossible and contributes to the recurrent disease faced by most patients. Although research into the impact of iron on glioblastoma has addressed proliferation, there has been little investigation into how cellular iron impacts the ability of glioblastoma cells to migrate-a key question, especially in the context of the diffuse spread observed in these tumors. Herein, we show that increasing cellular iron content results in decreased migratory capacity of human glioblastoma cells. The decrease in migratory capacity was accompanied by a decrease in cellular polarization in the direction of movement. Expression of CDC42, a Rho GTPase that is essential for both cellular migration and establishment of polarity in the direction of cell movement, was reduced upon iron treatment. We then analyzed a single-cell RNA-seq dataset of human glioblastoma samples and found that cells at the tumor periphery had a gene signature that is consistent with having lower levels of cellular iron. Altogether, our results suggest that cellular iron content is impacting glioblastoma cell migratory capacity and that cells with higher iron levels exhibit reduced motility.
MeSH term(s)	Humans ; Glioblastoma/metabolism ; Cell Movement/genetics ; Brain/metabolism ; Cell Line, Tumor ; Brain Neoplasms/metabolism ; Cell Proliferation
Language	English
Publishing date	2023-11-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202202157RR
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Zs.A 2266: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Multi-ancestry and multi-trait genome-wide association meta-analyses inform clinical risk prediction for systemic lupus erythematosus.

Khunsriraksakul, Chachrit / Li, Qinmengge / Markus, Havell / Patrick, Matthew T / Sauteraud, Renan / McGuire, Daniel / Wang, Xingyan / Wang, Chen / Wang, Lida / Chen, Siyuan / Shenoy, Ganesh / Li, Bingshan / Zhong, Xue / Olsen, Nancy J / Carrel, Laura / Tsoi, Lam C / Jiang, Bibo / Liu, Dajiang J

Nature communications

2023 Volume 14, Issue 1, Page(s) 668

Abstract: Systemic lupus erythematosus is a heritable autoimmune disease that predominantly affects young women. To improve our understanding of genetic etiology, we conduct multi-ancestry and multi-trait meta-analysis of genome-wide association studies, ... ...

Abstract	Systemic lupus erythematosus is a heritable autoimmune disease that predominantly affects young women. To improve our understanding of genetic etiology, we conduct multi-ancestry and multi-trait meta-analysis of genome-wide association studies, encompassing 12 systemic lupus erythematosus cohorts from 3 different ancestries and 10 genetically correlated autoimmune diseases, and identify 16 novel loci. We also perform transcriptome-wide association studies, computational drug repurposing analysis, and cell type enrichment analysis. We discover putative drug classes, including a histone deacetylase inhibitor that could be repurposed to treat lupus. We also identify multiple cell types enriched with putative target genes, such as non-classical monocytes and B cells, which may be targeted for future therapeutics. Using this newly assembled result, we further construct polygenic risk score models and demonstrate that integrating polygenic risk score with clinical lab biomarkers improves the diagnostic accuracy of systemic lupus erythematosus using the Vanderbilt BioVU and Michigan Genomics Initiative biobanks.
MeSH term(s)	Humans ; Female ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Lupus Erythematosus, Systemic ; Autoimmune Diseases ; Phenotype ; Polymorphism, Single Nucleotide
Language	English
Publishing date	2023-02-07
Publishing country	England
Document type	Meta-Analysis ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-36306-5
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Article ; Online: Integrating 3D genomic and epigenomic data to enhance target gene discovery and drug repurposing in transcriptome-wide association studies.

Khunsriraksakul, Chachrit / McGuire, Daniel / Sauteraud, Renan / Chen, Fang / Yang, Lina / Wang, Lida / Hughey, Jordan / Eckert, Scott / Dylan Weissenkampen, J / Shenoy, Ganesh / Marx, Olivia / Carrel, Laura / Jiang, Bibo / Liu, Dajiang J

Nature communications

2022 Volume 13, Issue 1, Page(s) 3258

Abstract: Transcriptome-wide association studies (TWAS) are popular approaches to test for association between imputed gene expression levels and traits of interest. Here, we propose an integrative method PUMICE (Prediction Using Models Informed by Chromatin ... ...

Abstract	Transcriptome-wide association studies (TWAS) are popular approaches to test for association between imputed gene expression levels and traits of interest. Here, we propose an integrative method PUMICE (Prediction Using Models Informed by Chromatin conformations and Epigenomics) to integrate 3D genomic and epigenomic data with expression quantitative trait loci (eQTL) to more accurately predict gene expressions. PUMICE helps define and prioritize regions that harbor cis-regulatory variants, which outperforms competing methods. We further describe an extension to our method PUMICE +, which jointly combines TWAS results from single- and multi-tissue models. Across 79 traits, PUMICE + identifies 22% more independent novel genes and increases median chi-square statistics values at known loci by 35% compared to the second-best method, as well as achieves the narrowest credible interval size. Lastly, we perform computational drug repurposing and confirm that PUMICE + outperforms other TWAS methods.
MeSH term(s)	Drug Repositioning ; Epigenomics ; Genetic Predisposition to Disease ; Genome-Wide Association Study/methods ; Genomics ; Humans ; Polymorphism, Single Nucleotide ; Transcriptome/genetics
Language	English
Publishing date	2022-06-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-30956-7
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