bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can nasal Staphylococcus aureus screening and decolonization prior to elective total joint arthroplasty reduce surgical site and prosthesis-related infections? A systematic review and meta-analysis
Authors: Zhu Xingyang , Sun Xiaobo , Zeng Yuqing , Feng Wenjun , Li Jie , Zeng Jianchun , Zeng Yirong 
Published: February 2020

Abstract
Background
Nasal Staphylococcus aureus (S. aureus) screening and decolonization has been widely used to reduce surgical site infections (SSIs) prior to total knee and hip arthroplasty (TKA and THA). However, it remains considerably controversial. The aim of this study was to ascertain whether this scheme could reduce SSIs and periprosthetic joint infections (PJIs) following elective primary total joint arthroplasty (TJA).

Methods
A systematic search was performed in MEDLINE, Embase, and the Cochrane Library until October, 2019. Outcomes of interest included SSI, PJI, superficial infection, and different bacterial species that caused infections. Data from eligible studies were then extracted and synthesized. Pooled odds ratios (OR) and 95% confidence intervals (CIs) were calculated. We also performed additional analyses to evaluate whether there were differences in postoperative SSIs caused by S. aureus or other bacteria.

Results
Nine studies were included in our meta-analysis. The pooled data elucidated that nasal S. aureus screening and decolonization dramatically mitigated the risk of SSI, PJI, and superficial infection compared to nondecolonization group. The analysis of bacterial species causing infection also showed that the S. aureus infections postoperative were significantly decreased in the decolonization group. However, there was no statistical difference in the SSI caused by other bacteria between the two groups.

Conclusion
S. aureus screening and decolonization prior to elective primary THA and TKA could significantly decrease the risk of SSI and PJI. However, more robust studies are needed to further evaluate the impact of S. aureus screening and decolonization on infection risk after TJA.
Acute kidney injury after primary total hip arthroplasty: a risk multiplier for complication, mortality, and healthcare utilization
Authors: Singh Jasvinder A. , Cleveland John D. 
Published: February 2020

Abstract
Objective
To assess whether acute kidney injury (AKI) is associated with more complications and higher healthcare utilization in people undergoing primary total hip arthroplasty (THA).

Methods
Using a retrospective cohort study design, we performed multivariable-adjusted logistic regression of the 1998–2014 US National Inpatient Sample data to assess the association of AKI with complications (infection, transfusion, revision, and mortality) and healthcare utilization (total hospital charges, discharge to a rehabilitation facility, length of hospital stay) post-THA. We calculated the odds ratio (OR) and 95% confidence intervals (CI).

Results
Adjusted for age, gender, race, income, underlying diagnosis, medical comorbidity, and the insurance payer, AKI in people who underwent primary THA was associated with significantly higher OR (95% CI) of (1) implant infection, 2.34 (95% CI, 1.87, 2.93); (2) transfusion, 2.46 (95% CI, 2.37, 2.56); (3) revision, 2.54 (95% CI, 2.16, 2.98); (4) death, 8.52 (95% CI, 7.47, 9.73); (5) total hospital charges above the median, 2.29 (95% CI, 1.99, 2.65); (6) discharge to a rehabilitation facility, 2.11 (95% CI, 2.02, 2.20); and (7) hospital stay > 3 days, 4.34 (95% CI, 4.16, 4.53).

Conclusion
Quality improvement initiatives with optimization of the peri-operative care to reduce AKI and subsequently AKI-associated complications and healthcare utilization are needed. Mechanisms of AKI-associated post-THA complications need further examination.
Strong convergence of an inertial iterative algorithm for variational inequality problem, generalized equilibrium problem, and fixed point problem in a Banach space
Authors: Alansari Monairah , Ali Rehan , Farid Mohammad 
Published: February 2020

AbstractWe propose and analyze an inertial iterative algorithm to approximate a common solution of generalized equilibrium problem, variational inequality problem, and fixed point problem in the framework of a 2-uniformly convex and uniformly smooth real Banach space. Further, we study the convergence analysis of our proposed iterative method. Finally, we give application and a numerical example to illustrate the applicability of the main algorithm.
Role of serum biomarkers and transcranial Doppler in predicting cerebral vasospasm after aneurysmal subarachnoid hemorrhage
Authors: Abdelnaseer Maged Mohammad , Nemr Ahmed Abdelkader , Ahmed Sandra Mohammad , Aboul fotouh Alshaimaa M. , Soliman Amro Mohammad Ahmed , El-Fiki Ahmed Abdullah , Osman Safinaz Hassan 
Published: February 2020

Abstract
Background
Aneurysmal subarachnoid hemorrhage (aSAH) can have serious consequences related to vasospasm and delayed cerebral ischemia (DCI). Serum biomarkers have emerged as a promising assessment tool to facilitate earlier diagnosis of cerebral vasospasm (CV) and to identify pre-clinical vessel narrowing.

Objectives
Our aim was to detect the predictive value of serum biomarkers such as von Willebrand factor (vWF), vascular endothelial growth factor (VEGF) and matrix metalloproteinase9 (MMP-9) in CV after aSAH.

Subjects and methods
Thirty five patients with recent aSAH were included. Patients were divided into two groups; 19 patients (CV group) and 16 patients (non-CV group). The CV group was further subdivided into 9 symptomatic (DCI) and 10 asymptomatic patients. All patients underwent transcranial Doppler (TCD) evaluations three times a week for 2 weeks measuring the mean flow velocities. Serum level of vWF, MMP-9, and VEGF were assessed twice (at onset and within 2 weeks).

Results
A statistically significant increase in serum biomarker levels was found in the CV group. Cutoff value for vWF, MMP-9, and VEGF were > 4985 ng/ml, > 495 ng/ml, and > 184 pg/ml, respectively. Statistically significant positive correlations were found between serum levels of biomarkers and degree of vasospasm. No difference was found in the biomarkers between symptomatic CV and asymptomatic CV.

Conclusion
Serum biomarkers are a reliable tool to predict CV following aSAH, their levels reflect the severity of vascular vasospasm, yet, they cannot predict DCI. TCD has a strong role in early detection, monitoring of post subarachnoid vasospasm and successfully capturing asymptomatic DCI.
Improvement in Patient-Reported Outcomes With Intensity-Modulated Radiotherapy (RT) Compared With Standard RT: A Report From the NRG Oncology RTOG 1203 Study
Authors: Yeung Anamaria R. , Pugh Stephanie L. , Klopp Ann H. , Gil Karen M. , Wenzel Lari , Westin Shannon N. , Gaffney David K. , Small William , Thompson Spencer , Doncals Desiree E. , Cantuaria Guilherme H.C. , Yaremko Brian P. , Chang Amy , Kundapur Vijayananda , Mohan Dasarahally S. , Haas Michael L. , Kim Yong Bae , Ferguson Catherine L. , Deshmukh Snehal , Bruner Deborah W. , Kachnic Lisa A. 
Published: February 2020

PURPOSE In oncology trials, the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) is the standard tool for reporting adverse events (AEs), but it may underreport symptoms experienced by patients. This analysis of the NRG Oncology RTOG 1203 compared symptom reporting by patients and clinicians during radiotherapy (RT). PATIENTS AND METHODS Patients with cervical or endometrial cancer requiring postoperative RT were randomly assigned to standard 4-field RT or intensity-modulated RT (IMRT). Patients completed the 6-item patient-reported outcomes version of the CTCAE (PRO-CTCAE) for GI toxicity assessing abdominal pain, diarrhea, and fecal incontinence at various time points. Patients reported symptoms on a 5-point scale. Clinicians recorded these AEs as CTCAE grades 1 to 5. Clinician- and patient-reported AEs were compared using McNemar’s test for rates > 0%. RESULTS Of 278 eligible patients, 234 consented and completed the PRO-CTCAE. Patients reported high-grade abdominal pain 19.1% ( P < .0001), high-grade diarrhea 38.5% ( P < .0001), and fecal incontinence 6.8% more frequently than clinicians. Similar effects were seen between grade ≥ 1 CTCAE toxicity and any-grade patient-reported toxicity. Between-arm comparison of patient-reported high-grade AEs revealed that at 5 weeks of RT, patients who received IMRT experienced fewer GI AEs than patients who received 4-field pelvic RT with regard to frequency of diarrhea (18.2% difference; P = .01), frequency of fecal incontinence (8.2% difference; P = .01), and interference of fecal incontinence (8.5% difference; P = .04). CONCLUSION Patient-reported AEs showed a reduction in symptoms with IMRT compared with standard RT, whereas clinician-reported AEs revealed no difference. Clinicians also underreported symptomatic GI AEs compared with patients. This suggests that patient-reported symptomatic AEs are important to assess in this disease setting.
Prostate-directed radiation therapy and overall survival for men with M1a prostate cancer.
Authors: Yang David Dewei , Butler Santino , Muralidhar Vinayak , Mahal Brandon Arvin Virgil , Martin Neil E. , Mouw Kent William , Nguyen Paul L. , King Martin T. , Orio Peter F. 
Published: February 2020

101 Background: A recent randomized controlled trial demonstrated that radiation therapy to the prostate improves overall survival for men with newly diagnosed metastatic prostate cancer with a low metastatic burden. Most patients in this trial had bony metastases (stage M1b). The benefit of prostate-directed radiation therapy for men with metastases limited to non-regional lymph nodes (stage M1a) is unknown. We investigated the association between prostate-directed radiation therapy and overall survival for men with M1a prostate cancer. Methods: We identified 2,079 men from the National Cancer Database who were newly diagnosed with M1a prostate adenocarcinoma from 2004 through 2014 and had data on the use of androgen deprivation therapy, chemotherapy, and radiation therapy. Median follow-up was estimated using the reverse Kaplan-Meier method. The association between radiation therapy to the prostate and overall survival was examined using multivariable Cox proportional hazards regression analysis. Results: Overall, 12.7% (264) of patients received radiation therapy to the prostate. Median follow-up was 4.6 years (95% confidence interval 4.3-4.8 years). On multivariable analysis, when accounting for the use of androgen deprivation therapy and chemotherapy, Gleason grade group, clinical tumor and nodal stage, and prostate-specific antigen level at diagnosis, the use of radiation therapy to the prostate was associated with a significant improvement in overall survival (adjusted hazard ratio 0.60, 95% confidence interval 0.49-0.74, P<0.001). Adjusted median overall survival was 3.3 years for patients who did not receive radiation therapy to the prostate compared to 5.5 years for patients who did. Conclusions: Similar to newly diagnosed M1b prostate cancer with a low metastatic burden, patients with M1a prostate cancer may also derive a significant overall survival benefit from receiving radiation therapy to the primary prostate tumor. The use of prostate-directed radiation therapy for M1a patients should be further investigated.
Overall survival using radium-223 (Ra223) in metastatic castrate-resistant prostate cancer (mCRPC) patients with and without DNA damage repair (DDR) defects.
Authors: van der Doelen Maarten J. , Isaacsson Velho Pedro , Slootbeek Peter H.J. , Pamidimarri Naga Samhita , Bormann Maren , van Helvert Sjoerd , Kroeze Leonie I. , van Oort Inge M. , Gerritsen Winald R. , Antonarakis Emmanuel S. , Mehra Niven 
Published: February 2020

121 Background: Ra223 is a therapeutic option for mCRPC patients (pts) with symptomatic bone metastases. DDR-defective prostate cancers, specifically those with homologous recombination deficiency (HRD), accumulate irreparable DNA damage following genotoxic treatment. This study assessed presence or absence of DDR alterations in mCRPC pts treated with Ra223, investigating the effect on efficacy and overall survival (OS). Methods: All pts included were treated with Ra223 and had genomic results from a comprehensive next-generation sequencing panel of DDR genes that directly or indirectly led to HRD, from primary or metastatic tissue. Exclusion criteria were prior platinum-based chemotherapy or treatment with poly-ADP ribose polymerase inhibitors (PARPi). Pts were grouped by presence (DDR+) or absence (DDR-) of pathogenic somatic and/or germline aberrations in DDR genes. Primary endpoint was OS, and secondary endpoints were time to alkaline phosphatase (ALP) progression, time to next systemic therapy and biochemical responses; comparing DDR+ and DDR– groups. Results: 93 pts were included in this two-centre retrospective study. Median age was 68 years. 56% received prior chemotherapy. Baseline characteristics where comparable between DDR status subgroups. 28 (30%) pts had mutations in DDR genes, most frequently occurring in ATM (8.6%), BRCA2 (6.5%), and CDK12 (4.3%) genes. DDR+ pts showed prolonged OS (median 36.3 vs. 17.0 months; HR 2.29; 95% CI 1.21-4.32; P= 0.01). Median time to alkaline phosphatase progression was 6.9 months for DDR+ pts and 5.8 months for DDR- pts (HR 1.48; 95% CI 0.87-2.50; P =0.15), and median time to next systemic therapy was 8.9 months for DDR+ pts and 7.3 months for DDR- pts (HR 1.58; 95% CI 0.94-2.64; P =0.08). A higher proportion of DDR+ pts completed Ra223 therapy (79% vs 47%; P= 0.05). No differences in biochemical (prostate-specific antigen, ALP) responses were seen. Conclusions: Pts harboring deleterious DDR aberrations more commonly completed Ra223, and derived a greater OS benefit. These findings need prospective confirmation, but support combination of Ra223 with PARPi or ATR inhibitors in DDR-defective mCRPC pts.
Surgical management versus combination radiotherapy in Gleason score 9-10 prostate cancer.
Authors: Dee Edward Christopher , King Martin T. , Butler Santino , Yu Zizi , Sha Sybil , Yang David Dewei , Mahal Brandon Arvin Virgil , Mouw Kent William , D'Amico Anthony Victor , Nguyen Paul L. , Muralidhar Vinayak 
Published: February 2020

135 Background: For men with Gleason score 9-10 prostate cancer, studies have demonstrated conflicting results on the outcomes from combination radiation therapy (ComboRT) with external beam radiation therapy plus brachytherapy boost versus radical prostatectomy (RP), with or without adjuvant radiation therapy (ART). Differences in patient selection and management may explain some of the disparate outcomes of prior reports. Methods: The Surveillance, Epidemiology, and End Results database identified 10,396 men managed with ComboRT versus RP (+/-ART). Competing-risks regression analysis with treatment propensity adjustment defined hazard ratios (aHR) for prostate cancer-specific mortality (PCSM), controlling for patient-specific demographic factors. To explore the possible effect of patient selection, analyses were conducted before and after excluding men from analysis if they had evidence-based indications for ART (adverse pathology, i.e. pT3-T4 or positive margins) but did not receive it. Results: Median age was 64 years; median follow-up was 69 months. Five-year PCSM was similar between patients treated with RP (with or without ART, regardless of pathologic features, N=8,934) and ComboRT (N=1,462) (6.9% vs 8.1%, aHR=0.94, 95% confidence interval [CI] 0.78–1.13, P=0.51). After excluding RP-treated men with adverse pathology who did not receive ART (N=4,527 excluded), patients treated with RP+/-ART (N=4,407) had improved 5-year PCSM compared with those treated with ComboRT (5.3% vs 8.1%, aHR=0.74, 95% CI 0.60–0.91, P=0.004). Conclusions: For Gleason 9-10 prostate cancer, ComboRT was associated with similar PCSM compared to RP, but risk-tailored surgical management may be associated with superior PCSM.
Circulating tumor cell (CTC) genomic signatures of hormone therapy resistance in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Gupta Santosh , Halabi Susan , Kemeny Gabor , Anand Monika , Nanus David M. , Giannakakou Paraskevi , George Daniel J. , Gregory Simon , Armstrong Andrew J. 
Published: February 2020

147 Background: Men with CTC AR-V7 + mCRPC have very poor outcomes when treated with enzalutamide/abiraterone. However, many men lack AR-V7. Here, we determined whether baseline or post-treatment DNA alterations in CTCs from AR-V7 negative mCRPC men could provide clinical utility in predicting outcomes with these hormonal therapies. Methods: We analyzed whole-genome copy number alterations (CNA) using array-comparative genomic hybridization (aCGH) in CTCs from 48 men (45 baseline and 28 progression), and whole-exome sequencing (WES) from 11 mCRPC men treated with abi/enza, longitudinally, and focused exclusively on AR-V7 negative men (N = 40) by the Epic-AR-V7 nuclear protein assay, and comparing those men who benefit from therapy vs. who do not. Results: We observed broad heterogeneity of CNAs between patients; common genomic alterations included gain in KDM6A (44%), FOXA1 (44%), MYCN (32%), and AR (38%), and loss in BRCA1 (30%) and PTEN (25%). Men who had the clinical benefit to abi/enza (n = 23, median PFS 10 mo) were more likely to have CTCs with genomic gains of ATM, HSD17B4, or PTEN, and loss of BRAF, ABL1, or NKX3-1. Likewise, men who did not benefit from abi/enza (n = 14, median PFS 2.6 mo) had CTCs with more copy number alterations than men who had clinical benefit (median 19.5 vs. 14, p = 0.01), and were enriched for gain of BRCA2, APC, KDM5D, SPARC, MYCN, AR, and CYP11B1, and loss of PTEN, CHD1, PHLPP1, and NCOR2. After progression on abi/enza, we observed clonal evolution of CTCs harboring gain of ATM, FOXA1, KDM6A, CYP11B1, MYC, APC, and NCOR2, and loss of NCOR1, ERG, and RUNX2. Several COSMIC-validated non-synonymous pathogenic exome mutations were detected in progressed or non-responding patients’ CTC DNA; TP53 (55 vs 27% at baseline), AKAP9 (36 vs 9%), CDK12, KMT2D, and BRAF (each 36 vs 18%), and BRD4 and SPOP (each 18 vs 0%). Conclusions: We demonstrate that specific CTC genomic profiles associated with TP53, PTEN, WNT, DNA repair, epigenetic, and AR signaling, as well as lineage plasticity pathways are associated with worse clinical outcomes in AR-V7 negative men with mCRPC treated with abi/enza. Further mechanistic and validation studies are warranted. Clinical trial information: NCT02269982.
MiR-27a-3p: An AR-modulatory microRNA with a distinct role in prostate cancer progression and therapy.
Authors: Kalofonou Foteini , Sita-Lumsden Ailsa , Leach Damien , Fletcher Claire , Waxman Jonathan , Bevan Charlotte L. 
Published: February 2020

193 Background: Prostate cancer (PCa) is an androgen dependent malignancy. PCa patients initially respond to androgen ablation but eventually the disease becomes castrate resistant. MicroRNAs (miRs) are considered to be master regulators of gene expression and could be potential biomarkers and therapeutic targets for PCa. We previously showed miR-27a-3p to be an androgen receptor (AR)-modulatory oncomiR, with a role in PCa progression. Methods: RNA sequencing was carried out on xenograft tumours treated with an inhibitory antisense oligonucleotide for miR-27a (ASO-27a), or control. Differentially expressed genes were cross-referenced with publicly available patient tissue datasets. ASO-27a was transfected in a panel of PCa cell lines mirroring disease progression, to verify changes in transcriptional and translational levels. Immunohistochemical analysis of encoded proteins was undertaken in a cohort of 46 PCa patients with Gleason 3+4 or 4+3 disease and compared with normal tissue-control. Results: Putative target genes tested included the tumour suppressor HIP2, the oncogenes SRC3, YAP, and PAX3, which can act both as oncogene and tumour suppressor. MRNA or protein levels of the majority of those genes tested were upregulated after ASO-27a treatment of PCa cell lines. In 22Rv1 cells, HIPK2 mRNA levels were significantly upregulated with ASO-27a (p = 0.0137), while protein levels were downregulated . PAX3 mRNA levels were significantly reduced by ASO-27a in 22Rv1 cells (p = 0.0364), while protein levels were significantly increased (p = 0.0112). Immunohistochemically, PAX3 protein was lower in Gleason 7 tumours than in normal tissue, while YAP expression was higher in patients with Gleason 4+3, relative to those with 3+4. SRC3 immunostaining was slightly, but not significantly, higher in patients with 3+4 compared to 4+3. Conclusions: MiR-27a-3p is an AR-modulatory oncomiR in PCa, with potential as a therapeutic target. MiR-27a interaction with its target genes and especially HIPK2, YAP, SRC3 and PAX3 could provide the basis for therapeutic advance in screening and in the treatment of castrate resistant disease, through ASO-27a inhibition.
Next-generation sequencing (NGS) of tumor tissue from >4000 men with metastatic castration-resistant prostate cancer (mCRPC): The PROfound phase III study experience.
Authors: Hussain Maha H. A. , Mateo Joaquin , Sandhu Shahneen Kaur , Fizazi Karim , Saad Fred , Shore Neal D. , Olmos David , Corcoran Claire , Sibilla Caroline , Kohlmann Alexander , Adelman Carrie A. , Elvin Julia Andrea , Goessl Carsten Dietrich , Burgents Joseph , De Bono Johann S. 
Published: February 2020

195 Background: The PROfound study (NCT02987543) showed that olaparib provides a statistically significant improvement in radiographic progression-free survival versus physician’s choice of enzalutamide or abiraterone in mCRPC patients (pts) with alterations in genes with a direct or indirect role in the homologous recombination repair (HRR) pathway. This is the largest study to date with central, prospective tumor tissue testing in pts with mCRPC. Here, we report learnings during testing in the PROfound study. Methods: An investigational clinical trial assay, based on the FoundationOne CDx NGS test developed in partnership with Foundation Medicine, Inc (FMI), was used to prospectively identify pts with qualifying alterations in ≥1 of 15 prespecified genes, including BRCA1, BRCA2 or ATM. Tumor testing was conducted centrally using archival or recent biopsy from primary or metastatic tissue. Results: Of 4047 pts who submitted tumor samples, 2792 (69%) were successfully sequenced and yielded a biomarker status. Categories for test failure (n=1255; 31%) were pathology review failure in 277 (6.8%) pts (eg estimated tumor fraction <20% or tumor volume <0.2 mm2), DNA extraction failure in 533 (13.2%) pts, and failure after DNA extraction in 280 (6.9%) pts, with 165 (4.1%) pts in >1 category. Regarding the sample disposition, approximately two-thirds of samples were from core needle biopsies, although higher success rates were observed with larger samples (ie prostatectomy). Samples were mainly from the prostate gland, with <5% from bone. Most samples were from archived tissue of primary tumors; only ~10% were from newly collected tissue. Test turnaround time, as well as representation of sample characteristics and country of origin relative to success rate, will be presented. Conclusions: The PROfound study has demonstrated that tissue testing to identify HRR alterations in men with mCRPC is feasible. Careful selection of high-quality tumor tissue samples is key to ensure success both at pathology review and during downstream steps of the NGS tissue testing process. Clinical trial information: NCT02987543.