bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic evaluation of CA19-9, D-dimer and TNFAIP3/A20 in patients with pancreatic ductal adenocarcinoma
Authors: Xu Peng , Wang XiaoDong , Qian JianJun , Li ZhengNan , Yao Jie , Xu AMan 
Published: February 2021

Abstract
This study aimed to explore the significance and prognostic value of serum tumor-associated carbohydrate antigen 19-9 (CA19-9), D-dimer, and tumor necrosis factor alpha-induced protein 3 (TNFAIP3/A20) in patients with pancreatic ductal adenocarcinoma (PDAC).
Our study included 148 patients treated for PDAC at Northern Jiangsu People's Hospital Affiliated to Yangzhou University from January 2012 to December 2016. Cutoff prognostic values were predicted using the receiver operating characteristic (ROC) curve. The Kaplan–Meier method was used to assess the survival rates of patients. Univariate and multivariate COX regression analyses were used to evaluate the prognostic factors.
The recommended cutoff values of neutrophil–lymphocyte rate (NLR), platelet-lymphocyte rate (PLR), CA19-9, and D-dimer were 2.04 (sensitivity, 0.59; specificity, 0.9; area under the ROC curve [AUC], 0.749; P < .001), 52.94 (sensitivity, 0.73; specificity, 0.95; AUC, 0.829; P < .001), 176.66 U/mL (sensitivity, 0.7; specificity, 0.9; AUC, 0.794; P < .001), and 1.18 mg/L (sensitivity, 0.82; specificity, 0.9; AUC, 0.845; P < .001), respectively. Positive TNFAIP3/A20 expression was considered as an inclusion criterion. Serum CA19-9 expression was related with lymph node metastasis (P = .010), tumor-lymph node-metastasis (TNM) stage (P < .001), and survival rate (P < .001). D-dimer was correlated with tumor differentiation grade (P = .014), tumor size (P = .045), TNM stage (P < .001), and survival rate (P < .001). TNFAIP3/A20 was correlated with tumor differentiation grade (P < .001), body mass index (BMI) (P < .001), TNM stage (P = .014), and survival rate (P < .001). Kaplan–Meier curves showed that PDAC patients had significant differences in CA19-9, D-dimer, and TNFAIP3/A20 expressions (P < .05). CA19-9, D-dimer, TNM stage, tumor differentiation grade, and TNFAIP3/A20 were independent prognostic markers for PDAC in univariate and multivariate COX analyses.
CA19-9, D-dimer, and TNFAIP3/A20 were found to be independent prognostic markers for PDAC patients.
Associations Between Copays, Coverage Limits for Opioid Use Disorder Medications, and Prescribing in Medicaid, 2018
Authors: Barenie Rachel E. , Kesselheim Aaron S. , Tsacogianis Theodore , Fischer Michael A. 
Published: February 2021

Background:
Opioid use disorder (OUD) affects millions of Americans, but only a fraction receive treatment. Many patients with OUD are enrolled in Medicaid, but elements of different state Medicaid programs’ drug benefit designs may impact patients’ access to life-saving care.

Objective:
To describe medication for OUD (mOUD) use in Medicaid and examine the relationship between mOUD use and state drug benefit design plans.

Design/Subjects:
Cross-sectional study using Medicaid State Drug Utilization Data from 2018 to quantify office-based mOUD and the Medicaid Behavioral Health Services Database to extract copay amounts and coverage limits for mOUD. We excluded states with <5% coverage and assessed for associations between copays or coverage limits and mOUD dispensing using simple linear regression.

Measures:
Proportion of mOUD prescriptions relative to all prescriptions, opioid prescriptions, and the state-level prevalence of pain reliever use disorder and association between copays, coverage limits and these proportions.

Results:
There was substantial variability in mOUD use. Although state Medicaid drug benefit designs also varied, we found no significant relationship between copay requirements (yes/no), coverage limits (yes/no), copay amount ($0–$0.99 vs. $1 or more), and mOUD utilization measures.

Conclusions:
Substantial state-level variation exists in mOUD use, but we did not find a significant association between copays or coverage limits and use in Medicaid. Further research is needed to assess other potential impacts of mOUD drug benefit design elements in Medicaid.
Circulating Cell-Free DNA in Pancreatic Head Adenocarcinoma Undergoing Pancreaticoduodenectomy
Authors: Wang Shin-E , Shyr Bor-Uei , Shyr Bor-Shiuan , Chen Shih-Chin , Chang Shih-Ching , Shyr Yi-Ming 
Published: February 2021

Objective
Circulating cell-free DNA (cfDNA) analysis is recently reported as a promising prognostic biomarker in various types of cancer. This study aimed to evaluate the role of cfDNA in pancreatic head adenocarcinoma.

Methods
Data for pancreatic head adenocarcinoma undergoing pancreaticoduodenectomy were studied for cfDNA. Prognostic factors were determined, and their correlation with cfDNA level was evaluated.

Results
The median of cfDNA for 97 cases was 7724 copies/mL, with a mean of 10,467, and ranging from 1856 to 44,203. Cell-free DNA was significantly higher in positive lymph node involvement and advanced stage III. Poor prognostic factors included high cfDNA level (>7724 copies/mL), abnormal carbohydrate antigen 19-9, abnormal carcinoembryonic antigen, and advanced stage. The 1- and 5-year survivals for those with high cfDNA were poorer, 70.2% and 21.2%, respectively, as compared with 93.4% and 23.7% for those with low cfDNA level. Only cfDNA level and stage were independent prognostic factors after multivariate analysis.

Conclusions
The level of cfDNA was correlated with tumor burden. Therefore, it could be an emerging survival predictor for resectable pancreatic head adenocarcinoma, and its detection might be a promising liquid biopsy to monitor both tumor progression and treatment response.
An Updated Systematic Review With Meta-analysis
Authors: Yu Chen , Zhang Yuelun , Yang Qiao , Lee Peter , Windsor John Albert , Wu Dong 
Published: February 2021

Objectives
The aim of this study was to systematically review the clinical outcomes of all randomized controlled trials of patients with severe acute pancreatitis (SAP) and treated with pre/pro/synbiotics.

Methods
A systematic literature search of the MEDLINE, Embase, clinicaltrials.gov, and the Cochrane Central Register of Controlled Trials was conducted. Eligible studies were randomized controlled trials that evaluated the clinical outcomes of patients with SAP treated with pre/pro/synbiotics.

Results
Eleven trials comprising 930 patients were included. Patients treated with pre/pro/synbiotics had a significantly shorter hospital stay [weighted mean difference, −4.33 days; 95% confidence interval (CI), −7.71 to −0.95; P = 0.010; I
2 = 66.9%] compared with control. In a subgroup analysis where only patients classified as SAP were included, those treated with pre/pro/synbiotics had lower risk of single- or multiple-organ failure (relative risk, 0.62; 95% CI, 0.44–0.88; P = 0.995; I
2 = 0.0%) and decreased hospital stay (weighted mean difference, −0.65 days; 95% CI, −0.90 to −0.41; P = 0.121; I
2 = 45.3%) compared with control.

Conclusions
Patients with SAP treated with pre/pro/synbiotics did not have a worse clinical outcome and had lower risk of organ failure and duration of hospital stay. Further studies should examine the optimal timing, type, and dosages of these promising treatments.
Inhibition of Stearoyl-CoA Desaturase Induces the Unfolded Protein Response in Pancreatic Tumors and Suppresses Their Growth
Authors: Skrypek Kaitlin , Balog Steven , Eriguchi Yoshihiro , Asahina Kinji 
Published: February 2021

Objective
Pancreatic ductal adenocarcinoma is the fourth-leading cause of cancer death in the United States, and there is an urgent need for effective therapies. Stearoyl-CoA desaturase (SCD) is an enzyme localized in the endoplasmic reticulum and generates monounsaturated fatty acid from saturated fatty acid. In this study, we examined the role of SCD in pancreatic cancer.

Methods
We isolated epithelial cell adhesion molecule-positive pancreatic tumors from the Pdx1
Cre;LSL-Kras
G12D mouse and formed organoids in Matrigel. Using a SCD inhibitor, A939572, we tested its effects on growth and cell death in tumor organoids, tumors developed in the Pdx1
Cre;LSL-Kras
G12D mouse, and a human pancreatic ductal adenocarcinoma cell line, PANC-1.

Results
A939572 treatment rapidly induced degeneration of mouse tumor organoids and activated the unfolded protein response (UPR). Cotreatment of oleic acid, but not stearic acid, reduced the UPR in the organoids and rescued the inhibitory effect of the SCD inhibitor on their growth. Administration of A939572 to Pdx1
Cre;LSL-Kras
G12D mice caused cell death in early pancreatic tumors, but not in acini or islets. The SCD inhibitor induced the UPR in PANC-1 and suppressed their growth but did not induce cell death.

Conclusions
The inhibition of the SCD enzyme causes an UPR and cell death in early pancreatic tumors.
The Unique Microbiome and Immunity in Pancreatic Cancer
Authors: Wei Xin , Mei Chunlei , Li Xixi , Xie Yingjun 
Published: February 2021

Abstract
Microorganisms can help maintain homeostasis in humans by providing nutrition, maintaining hormone balance, and regulating inflammatory responses. In the case of imbalances, these microbes can cause various diseases, even malignancy. Pancreatic cancer (PC) is characterized by high tumor invasiveness, distant metastasis, and insensitivity to traditional chemotherapeutic drugs, and it is confirmed that PC is closely related to microorganisms. Recently, most studies based on clinical samples or case reports discussed the positive or negative relationships between microorganisms and PC. However, the specific mechanisms are blurry, especially the involved immunological pathways, and the roles of beneficial flora have usually been ignored. We reviewed studies published through September 2020 as identified using PubMed, MEDLINE, and Web of Science. We mainly introduced the traits of oral, gastrointestinal, and intratumoral microbes in PC and summarized the roles of these microbes in tumorigenesis and tumoral development through immunological pathways, in addition to illustrating the relationships between metabolic diseases with PC by microorganism. In addition, we identified microorganisms as biomarkers for early diagnosis and immunotherapy. This review will be significant for greater understanding the effect of microorganisms in PC and provide more meaningful guidance for future clinical applications.
Increasing Prevalence of Anxiety and Depression Disorders After Diagnosis of Chronic Pancreatitis
Authors: Alkhayyat Motasem , Abou Saleh Mohannad , Coronado Wendy , Abureesh Mohammad , Al-otoom Omaymah , Qapaja Thabet , Mansoor Emad , Simons-Linares C. Roberto , Stevens Tyler , Chahal Prabhleen 
Published: February 2021

Objectives
Chronic pancreatitis (CP) is often associated with poor quality of life. Only a few small associative studies have reported the prevalence of mood disorders in CP. Using a large database, we sought to describe the epidemiology and risk association of anxiety and depression in CP and evaluate their outcomes.

Methods
A multicenter database (Explorys), an aggregate of electronic health record data from 26 US healthcare systems, was surveyed. A cohort of patients with a diagnosis of CP between 2014 and 2019 was identified. Within this cohort, rates of anxiety and depression were calculated. Demographics, comorbidities, and outcomes were described.

Results
Of the 30,276,810 individuals in the database (2014–2019), 67,260 patients had a CP diagnosis (0.22%). When compared with patients with no history of CP, patients with CP were more likely to develop anxiety (odds ratio, 6.94; 95% confidence interval, 6.85–7.04) and depression (odds ratio, 5.09; 95% confidence interval, 5.01–5.17). Chronic pancreatitis patients with depression had an increased risk of suicidal ideation compared with controls.

Conclusions
Patients with CP are at a higher risk of developing anxiety and depression compared with those without CP, with overall worse outcomes. Clinicians should screen CP patients and make appropriate referral to psychiatry when indicated.
Clinical Significance of Inflammation Markers in Predicting the Severity of Acute Pancreatitis
Authors: Pian Guangzhe , Li Hao , Piao Yongjun 
Published: February 2021

Objectives
Acute pancreatitis (AP) is an inflammatory disease of the pancreas. We analyzed changes in inflammation markers to explore the clinical significance of using these markers to predict the severity of AP.

Methods
The study included 169 patients (severe AP = 50 and nonsevere AP = 119) admitted to Yanbian University Hospital between January 2015 and July 2017. The neutrophil-to-lymphocyte ratio (NLR), prognostic nutrition index (PNI), lymphocyte-to-monocyte ratio, red blood cell distribution width coefficient of variation, mean platelet volume, platelet-to-lymphocyte ratio, and red blood cell distribution width-to-platelet ratio of the patients were detected after admission. Correlations between AP severity and various inflammatory markers were statistically analyzed.

Results
The results indicated that the NLR on the first day after admission (area under the curve, 0.824; 95% confidence interval, 0.753–0.896) and the PNI on the third day after admission (area under the curve, 0.814; 95% confidence interval, 0.753–0.896) had more significance than other inflammation markers in predicting the severity of AP. In AP patients, the NLR showed a gradual decline, and the PNI initially decreased and then increased.

Conclusions
The NLR and PNI can provide new reference values for predicting the severity of AP.
Sex Cord Stromal Tumors in Children and Adolescents: A First Report by The South African Children’s Cancer Study Group (1990-2015)
Authors: Hendricks Marc , Cois Annibale , Geel Jennifer , van Heerden Jaques , Naidu Gita , du Plessis Jan , Bassingthwaighte Mairi , van Zyl Anel , Uys Ronelle , Bϋchner Ane , Rowe Biance , Omar Fareed , Mahlachana Ngoakoane , Thomas Karla , Vermeulen Johani , Davidson Alan , Donald Kirsty A. , Kruger Mariana 
Published: February 2021

Objectives:
Pediatric sex cord stromal tumors (SCSTs) are extremely rare and there are no reported data from Africa. The authors evaluated the outcomes of children and adolescents with biopsy-proven SCSTs in preparation for the introduction of a national protocol.

Materials and Methods:
Retrospective data were collated from 9 South African pediatric oncology units from January 1990 to December 2015. Kaplan-Meier analysis was performed to estimate overall survival (OS) and event-free survival.

Results:
Twenty-three patients were diagnosed with SCSTs, 3 male and 20 female individuals, during the study period. Histologies included 1 thecoma, 9 Sertoli-Leydig cell tumors, and 13 juvenile granulosa cell tumors. Stage I tumors predominated (n=14; 60.9%), with 2 stage II (8.7%), 5 stage III (21.7%), and 2 stage IV tumors (8.7%). The upfront resection rate was 91.3% with no reported surgical morbidity or mortality and an OS of 82.1%. Chemotherapy approaches were not standardized. Most children (81.8%), except 2, had recognized platinum-based regimens. Chemotherapy-related toxicity was minimal and acceptable. Assessment of glomerular filtration rate and audiology assessments were infrequent and not standardized. Three patients were lost to follow-up.

Conclusions:
Although the numbers in this cohort are small, this study represents the first national cohort in Africa. The 5-year OS of 82.1% was encouraging. Standardized management of rare tumors like SCSTs is critical to improve ensure OS and address potential long-term sequelae.
Is Posaconazole Really Effective in Adolescent patients as a Prophylactic Agent: Experience of a Tertiary Care Center
Authors: Arikan Kamile , Aytac Selin , Büyükcam Ayse , Cengiz Ali B. , Cetinkaya Fahriye D. , Cetin Mualla , Ozsurekci Yasemin , Ceyhan Mehmet , Kara Ates 
Published: February 2021

Background:
Invasive fungal infections (IFIs) are a leading cause of morbidity and death in immunocompromised patients. Data on efficacy and pharmacokinetics of posaconazole in pediatric patients are rare (1 to 5). Herein, we retrospectively analyzed adolescent patients who had received posaconazole as antifungal prophylaxis.

Methods:
We retrospectively analyzed patients who received posaconazole as primary or secondary antifungal prophylaxis.

Results:
A total of 34 adolescent patients, 19 men (55.9%) and 15 women (44.1%) with a mean age of 15.8±2.1 years were included. Twenty-five of 34 (73.5%) patients were on primary and nine of 34 (26.5%) patients were on secondary antifungal prophylaxis. Diagnosis of the patients receiving posaconazole as primary antifungal prophylaxis were acute myeloid leukemia (n=12, 48%), hematopoietic stem cell transplantation (n=7, 28%), acute lymphoblastic leukemia (n=5, 20%), and Fanconi aplastic anemia (n=1, 4%). Five patients (55.6%) with hematopoietic stem cell transplantation, 1 patient with acute myeloid leukemia (11.1%), 1 patient with Fanconi aplastic anemia (11.1%), and 2 (22.2%) patients with chronic granulomatous disease received posaconazole as secondary antifungal prophylaxis. Twelve of 25 (48%) patients receiving posaconazole as primary antifungal prophylaxis were complicated by IFI; 4 of them were proven, 6 probable, and 2 with possible IFI. Three of 9 patients (33.3%) receiving posaconazole as secondary antifungal prophylaxis was complicated by IFI (P=0.29), 2 of them were probable and 1 was possible IFI. Five of 25 patients (20%) receiving posaconazole as primary prophylaxis died because of IFI.

Conclusion:
Improvement of antifungal prophylaxis in patients with high risk of invasive infections seems clearly necessary, and analyzing serum posaconazole levels and individualizing dosing may be 1 approach to improve outcomes.
Pediatric Neurodevelopmental Delays in Children 0 to 5 Years of Age With Sickle Cell Disease: A Systematic Literature Review
Authors: Knight La’Kita M.J. , King Allison A. , Strouse John J. , Tanabe Paula 
Published: February 2021

Introduction:
Sickle cell disease (SCD) is the most common abnormal genetic blood disease that affects ∼100,000 Americans. Approximately 20% to 37% of children with sickle cell anemia have silent cerebral infarcts by the age of 14 years old. Neurocognitive deficits are identified in infants and preschool children with SCD. The purpose of this systematic literature review is to provide a comprehensive understanding of the prevalence, severity, and the associated risk factors for neurodevelopmental delays (NDDs) in children with SCD 5 years of age and younger.

Methods:
Systematic search of 6 databases identified 2467 potentially relevant publications and 8 were identified through a manual search. Only 24 articles met the inclusion criteria.

Results:
We identified an increased prevalence of NDDs (cognitive, motor, or both). Children experienced deficits with language, attention and behavior, executive functioning, school readiness and/or academic performance, and motor skills (fine and gross motor functioning). Risk factors include silent cerebral infarcts and strokes, SCD genotype (HbSS>HbSC), other biologic, and social factors.

Conclusion:
NDDs are common in children ages 0 to 5 years old with SCD. There is an opportunity to improve adherence to national guideline recommendations and early detection practices by pediatricians, hematologists, and other health care providers.
Impact of the COVID-19 pandemic on the pharmacological, physical, and psychological treatments of pain: findings from the Chronic Pain & COVID-19 Pan-Canadian Study
Authors: Lacasse Anaïs , Pagé M. Gabrielle , Dassieu Lise , Sourial Nadia , Janelle-Montcalm Audrée , Dorais Marc , Nguena Nguefack Hermine Lore , Godbout-Parent Marimée , Hudspith Maria , Moor Gregg , Sutton Kathryn , Thompson James M. , Choinière Manon 
Published: February 2021

Abstract

Introduction:
Multimodal treatment is recognized as the optimal paradigm for the management of chronic pain (CP). Careful balance between pharmacological and physical/psychological approaches is thus desirable but can be easily disrupted.

Objectives:
This study aimed at exploring the impact of the COVID-19 pandemic on pharmacological and physical/psychological treatments of CP.

Methods:
A Pan-Canadian cross-sectional web-based study was conducted between April 16th and May 31st 2020 among adults living with CP when the country was in the ascending slope of the first COVID-19 pandemic wave.

Results:
A total of 2864 participants shared their treatment experience (mean age: 49.7 years and women: 83.5%). Among medication users (n = 2533), 38.3% reported changes in their pharmacological pain treatment. The main reasons were as follows: (1) changes in pain symptoms, (2) lack of access to prescribers/cancellation of medical appointments, and (3) increased medication intake in compensation for stopping physical/psychological treatments because of the pandemic. Among participants who used physical/psychological pain management approaches before the pandemic (n = 2467), 68.3% had to modify their treatments or self-management strategies. Common reasons were lack of access to clinics/exercise facilities and the need to compensate for having to stop another type of physical/psychological treatment because of the pandemic-related public health safety measures.

Conclusions:
Our study underlines the negative impact of the COVID-19 pandemic on access to pain relief, which is considered a fundamental human right. Results will help to justify resource allocation and inform the development of interventions to be better prepared for waves to come and future health crises.
Population Viral Load, Viremia, and Recent HIV-1 Infections: Findings From Population-Based HIV Impact Assessments (PHIAs) in Zimbabwe, Malawi, and Zambia
Authors: Farahani Mansoor , Radin Elizabeth , Saito Suzue , Sachathep Karampreet K. , Hladik Wolfgang , Voetsch Andrew C. , Auld Andrew F. , Balachandra Shirish , Tippett Barr Beth A. , Low Andrea , Smart Theodore F. , Musuka Godfrey , Jonnalagadda Sasi , Hakim Avi J. , Wadonda-Kabondo Nellie W. , Jahn Andreas , Mugurungi Owen , Williams Daniel B. , Barradas Danielle T. , Payne Danielle , Parekh Bharat , Patel Hetal , Wiesner Lubbe , Hoos David , Justman Jessica E. 
Published: February 2021

Background:
HIV population viral load (PVL) can reflect antiretroviral therapy program effectiveness and transmission potential in a community. Using nationally representative data from household surveys conducted in Zimbabwe, Malawi, and Zambia in 2015–16, we examined the association between various VL measures and the probability of at least one recent HIV-1 infection in the community.

Methods:
We used limiting-antigen avidity enzyme immunoassay, viral load suppression (VLS) (HIV RNA <1000 copies/mL), and antiretrovirals in the blood to identify recent HIV-1 cases.

Results:
Among 1510 enumeration areas (EAs) across the 3 surveys, 52,036 adults aged 15–59 years resided in 1363 (90.3%) EAs with at least one HIV-positive adult consenting to interview and blood draw and whose VL was tested. Mean HIV prevalence across these EAs was 13.1% [95% confidence intervals (CI) 12.7 to 13.5]. Mean VLS prevalence across these EAs was 58.7% (95% CI: 57.3 to 60.0). In multivariable analysis, PVL was associated with a recent HIV-1 case in that EA (adjusted odds ratio: 1.4, 95% CI: 1.2 to 1.6, P = 0.001). VLS prevalence was inversely correlated with recent infections (adjusted odds ratio: 0.3, 95% CI: 0.1 to 0.6, P = 0.004). The 90-90-90 indicators, namely, the prevalence of HIV diagnosis, antiretroviral therapy coverage, and VLS at the EA level, were inversely correlated with HIV recency at the EA level.

Conclusions:
We found a strong association between PVL and VLS prevalence and recent HIV-1 infection at the EA level across 3 southern African countries with generalized HIV epidemics. These results suggest that population-based measures of VLS in communities may serve as a proxy for epidemic control.