tbuckley/cabot-search huggingface dataset:
Analysis of feasibility and survival in repeated cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in appendiceal cancer with peritoneal dissemination.
Authors: Josh Karpes, Roneil Parikh, Raphael Shamavonian, Nayef Alzahrani, David L. Morris
Journal: Journal of Clinical Oncology (2019)

e15702 Background: CRS/HIPEC has been established as the method of choice for the management of peritoneal dissemination from appendiceal cancer. With recurrence rates after first surgery as high as 44%, re-do CRS/HIPEC is evolving as an effective recurrent treatment regime. This analysis examines the feasibility of repeated CRS/HIPEC for patients with appendiceal cancer with peritoneal dissemination and evaluates the survival outcomes. Methods: A retrospective cohort study of 1074 patients who had CRS/HIPEC procedures and had a recorded tumour grade from 1996 to 2017 was performed. Morbidity and mortality as well as the survival effect was analysed. Tumour grade was divided into low grade: diffuse peritoneal adenomucinosis (DPAM); and high grade: peritoneal mucinous carcinomatosis (PMCA). Results: Initial CRS/HIPEC comprised of 991 patients, with 148 of those undergoing repeated CRS/HIPEC for appendiceal cancer with peritoneal dissemination. The overall survival for patients with DPAM who had only one CRS/HIPEC was 248 months with a five-year survival of 80%, compared to an overall survival of 75 months and five-year survival of 54% in those who had repeated CRS/HIPEC. For patients with PMCA, the overall survival of those who only had one CRS/HIPEC was 63 months with a five-year survival of 47%, compared to an overall survival of 52 months and five-year survival of 44% in those who had repeated CRS/HIPEC. There was no statistically significant difference in the morbidity and mortality for patients who had repeated CRS/HIPEC for management of appendiceal cancer with peritoneal metastases when compared to those who only had one. Conclusions: This study suggests that re-do CRS/HIPEC is a feasible and effective treatment regime in the management of tumour recurrence in appendiceal cancer with peritoneal dissemination, with no difference in the morbidity and mortality of patients who had repeated CRS/HIPEC compared to only one procedure.
Surface bioactivation of PEEK by neutral atom beam technology
Authors: Joseph Khoury, Irina Selezneva, Sergei Pestov, Vadim Tarassov, Artem Ermakov, Andrey Mikheev, Mikhail Lazov, Sean R. Kirkpatrick, Dmitry Shashkov, Alexandre Smolkov
Journal: Bioactive Materials (2019)

Polyetheretherketone (PEEK) is an alternative to metallic implants and a material of choice in many applications, including orthopedic, spinal, trauma, and dental. While titanium (Ti) and Ti-alloys are widely used in many intraosseous implants due to its biocompatibility and ability to osseointegrate, negatives include stiffness which contributes to shear stress, radio-opacity, and Ti-sensitivity. Many surgeons prefer to use PEEK due to its biocompatibility, similar elasticity to bone, and radiolucency, however, due to its inert properties, it fails to fully integrate with bone. Accelerated Neutral Atom Beam (ANAB) technology has been successfully employed to demonstrate enhanced bioactivity of PEEK both in vitro and in vivo. In this study, we further characterize surfaces of PEEK modified by ANAB as well as elucidate attachment and genetic effects of dental pulp stem cells (DPSC) exposed to these surfaces. ANAB modification resulted in decreased contact angle at 72.9 ± 4.5° as compared to 92.4 ± 8.5° for control (p < 0.01) and a decreased average surface roughness, however with a nano-textured surface profile. ANAB treatment also increased the ability of DPSC attachment and proliferation with considerable genetic differences showing earlier progression towards osteogenic differentiation. This surface modification is achieved without adding a coating or changing the chemical composition of the PEEK material. Taken together, we show that ANAB processing of PEEK surface enhances the bioactivity of implantable medical devices without an additive or a coating.
Author's reply to: Ankylosing spondylitis: evidence for a non-HLA-B*27 protective effect, Sjef Van Der Linden, Desieree Van Der Heijde
Authors: Matthew Brown, Paul Wordsworth
Journal: Annals of the Rheumatic Diseases (1998)

As mentioned in the letter by van der Linden and van der Heijde, Jurgen Braun’s excellent recent paper describing a survey of blood donors by questionnaire, clinical, and magnetic resonance imaging examinations revealed a prevalence of ankylosing spondylitis in B27 positive blood donors (6.4%)1-1 very similar to that reported by Gran et al(6.7%).1-2 It is probable that some of the differences in reported prevalence of ankylosing spondylitis by the various studies are because of methodological differences.
Evaluation of cancer patients’ perspectives on weight management counseling at a comprehensive cancer center.
Authors: Damien Mikael Hansra, Cynthia Daniels, Ricardo H. Alvarez
Journal: Journal of Clinical Oncology (2019)

e18041 Background: Over 2/3 of Americans are Overweight (OW) or obese (OB). Being OW or OB is a risk factor for a variety of cancers &amp; denotes a worse prognosis for some. Evidenced based strategies on management of OW &amp; OB patients (pts) are lacking. Data shows the majority of physicians are OW &amp; OB and confidence in obesity counseling in these individuals is less compared with normal weight (NW) counterparts. Here we report the results of a survey on cancer pt’s opinions weight management counseling. Methods: An HRPP exemption was obtained. Pts asked to complete a 20-question (Q) survey. Clinical info collected: age, race, cancer type, weight class (underweight, NW, OW, OB, unsure but likely overweight). Survey Qs asked about optimal timing, type of weight counseling preferences. Also, Qs regarding importance of their oncologists (ONCO) BMI assessed. Secondary Qs about pt risk factors for obesity, pt willingness, &amp; pt preferred modalities to change dietary &amp; exercise habits also assessed. Statistical analysis: One-way ANOVA used to compare mean responses. P-values reported α = 0.05. Results: 245 cancer pts completed the survey. Demographics: 53% white, 37% black, 8% multiracial, 1% American Indian, 1% Asian. Majority of pts 51-65 years old (55%) and female ( &gt; 75%). 71% (175/245) of pts were OW or OB vs. 29% (70/245) of pts with normal weight. 78% (191/245) of pts had breast cancer vs. 22% (54/245) other cancers. Main results: The best time for an ONCO to address weight reduction with pts is? “Anytime” = 45% (111/245), “First visit” = 27% (65/245), “After primary treatment” = 27% (65/245), “Never” = 1% (2/245) (p &lt; 0.01). The approach pts prefer ONCO use to counsel on weight reduction is? “Educational approach” = 26% (65/245), “Direct approach” = 24% (59/245), “Passive approach” = 8% (20/245), “Passive &amp; educational” = 18% (44/245), “Direct &amp; educational” = 18% (43/245), “Other approaches” = 5% (12/245), “No approach, I don’t want counseling” = 1% (2/245) (p &lt; 0.01). Who would you listen to MOST about weight loss advice? “Normal weight ONCO” = 41% (101/245), “The BMI of my ONCO does not matter” = 53% (131/245), “OB or OW” 5% (13/245) (p &lt; 0.01). Results of secondary Qs included in presentation. Conclusions: Almost all pts would like to discuss weight loss with their oncologist on the first visit or after primary treatment has been completed. Also, most pts would like to receive counseling by their oncologist regardless of their oncologist’s weight. Furthermore, pts seem to prefer education about why weight loss is important be included in their weight loss counseling.
Correlation of HERVK with efficacy on anti-PD-1/PD-L1 therapy in a pilot metagenomics study on Chinese advanced lung cancer patients.
Authors: Haitao Tao, Yi Hu
Journal: Journal of Clinical Oncology (2019)

e14046 Background: Patient selection for PD-1 inhibitors in NSCLC is still based on imperfect screening biomarkers, including PD-L1 expression and tumor mutational burden(TMB).There are several reports show certain bacteria or virus infections are correlated with efficacy and prognosis on PD-1 inhibitors treatment. In order to explore more potential biomarkers for anti-PD-1 therapy, we investigate whether we can discover microorganisms in Chinese lung cancer patients and whether certain microorganism are correlated with efficacy or prognosis on anti-PD-1 therapy using metagenomics technology. Methods: In this study, 30 advanced lung cancer patient were enrolled, including 15 cases of adenocarcinoma, 12 cases of squamous carcinoma, 2 cases of Small cell lung cancer. 10 patients received PD-1/PD-L1 inhibitors as first-line therapy and other patients as second-line therapy. Among these 30 patients, 15 PR,1 CR, 10 PD, 4 SD according to RECIST 1.1. Plasma cell-free DNA (cfDNA) were collected from these patients prior to anti-PD-1 treatment and whole-genome sequencing of cfDNA at average coverage 5X was performed on Illumina NovaSeq in 2 ×150bp length model. A bioinformatics pipeline composed of 4 tools: BWA/Sambama/Kraken2/Bracken, was constructed to analyze the sequencing data. Non-human derived reads were extracted by sambama from the bam file that generated by BWA. Bacteria/Virus abundance in each sample was estimated through Bracken, followed by bac/vir database alignment in Kraken2. Results: In our pilot study, 4 patients were selected for metagenomics sequencing(1CR, 1PR, 2PD). Interestingly, over 100 different microbial sequence were detected in every patient. Compare microorganism in CR+PR patients to PD patients, Human endogenous retrovirus K (HERVK) were quite abundant in CR/PR patients but not in PD patients: 5.6 times more abundant in CR/PR patients comparing to PD patients. (HERVK abundance: CR:PR:PD = 1.20% : 0.32% : (0.17%, 0.10%)). HERVK is a family of human endogenous retroviruses associated with certain malignant tumors, studies have indicated that HERVK may trigger an antigen specific immune response for certain cancer patients. Conclusions: Metagenomics sequencing on plasma cfDNA could be a potential biomarker discovery approach to identify prognostic biomarkers for anti-PD-1 therapy. HERVK are correlated with efficacy on anti-PD-1 treatment in our pilot study, however more thorough investigation need to be conducted to confirm whether HERVK can be served as efficacy biomarkers for anti-PD-1.
FRI0226 LOW EXPRESSION OF ESTROGEN RECEPTOR BETA IN RENAL TUBULAR EPITHELIAL CELL MAY CONTRIBUTE TO HYPERURICEMIA IN PREMENOPAUNITED STATES OF AMERICAL FEMALE SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS
Authors: Haijun Liu, Xiaoyan Cai, Lie Dai, MA Jianda, Yingqian Mo, Minyan Xie
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> We have reported that the incidence of hyperuricemia of young female systemic lupus erythematosus (SLE) patients was higher than that of healthy young women<sup>[1]</sup>.Whether the estrogen receptor (ER) expressed in renal tubular tissue contributes to it? There are few reports yet. <h3>Objectives</h3> To investigate the expression of ERs in the renal tubular cells and their relationship with serum uric acid (UA) levels in premenopausal female SLE patients. <h3>Methods</h3> Eighteen kidney biopsy specimens of premenopausal female SLE patients served as the lupus nephritis group (LN group), and 12 specimens of premenopausal female IgA nephropaty patients served as the IgA group. Serum UA levels and kidney index were collected, and the expression of ERs in the renal tubular epithelial cell of the two groups were determined by immunohistochemistry. According to the percentage of the positive stained cells, the semiquantitative analysis was made. The expressions of ERs, including ERα and ERβ, of the two groups were compared, and the relationship between the expression of ERs and serum UA levels were analyzed with linear regression analysis. <h3>Results</h3> 1. The mean ages of the LN group and the IgA group were 27.39±8.09 years and 33.08±5.45 years, respectively, with significantly different (t=2.128, p=0.042). There was no renal failure subject in both groups (CRE level above 120μmol/l), and all the SLE patients were at stage of onset. 2. Mean UA level of the LN group was significantly higher than that of the IgA group (t=-3.149, P=0.004), and the CRE level of the two groups were similar (t=-0.109, P=0.914) (table1). 3. In each group, ERβ was well expressed in the tubular epithelial cells, and no in kidney glomeruli. In contrast, ERα was not expresssed in the renal tissues of both groups (figure1). 4. The median score of ERβ expression in the LN group was remarkable lower than that of the IgA group (z=-2.080, P=0.038, table 1). 5.Linear regression analysis indicated that ERβ expression scores of the total 30 patients had significantly negative correlation with serum UA levels (t=-2.141, P= 0.041, table2). <h3>Conclusion</h3> 1. Low expression of ERβ in renal tubular epithelial cell may contribute to hyperuricemia in premenopausal female SLE patients. 2. ERα showed no expression in LN and IgA nephropaty kidney tissues. <h3>References</h3> [1] Haijun Liu, Xiaoyan Cai, Lie Dai, et al. Elevated uric acid levels in premenopausal female systemic lupus erythematosus patients: association with potential or existing renal damage. Eur J Inflamm,2018,16:1-6. <h3>Disclosure of Interests</h3> None declared
Sustained correction of associative learning deficits after brief, early treatment in a rat model of Fragile X Syndrome
Authors: Antonis Asiminas, Adam D. Jackson, Susana R. Louros, Sally M. Till, Teresa Spano, Owen Dando, Mark F. Bear, Sumantra Chattarji, Giles E. Hardingham, Emily K. Osterweil, David J. A. Wyllie, Emma R. Wood, Peter C. Kind
Journal: Science Translational Medicine (2019)

Brief, early treatments with lovastatin provide long-lasting rescue of associative memory deficits in a rat model of Fragile X.
The Highly Recurrent PP2A Aα-Subunit Mutation P179R Alters Protein Structure and Impairs PP2A Enzyme Function to Promote Endometrial Tumorigenesis
Authors: Sarah E. Taylor, Caitlin M. O'Connor, Zhizhi Wang, Guobo Shen, Haichi Song, Daniel Leonard, Jaya Sangodkar, Corinne LaVasseur, Stefanie Avril, Steven Waggoner, Kristine Zanotti, Amy J. Armstrong, Christa Nagel, Kimberly Resnick, Sareena Singh, Mark W. Jackson, Wenqing Xu, Shozeb Haider, Analisa DiFeo, Goutham Narla
Journal: Cancer Research (2019)

Somatic mutation of the protein phosphatase 2A (PP2A) Aα-subunit gene PPP2R1A is highly prevalent in high-grade endometrial carcinoma. The structural, molecular, and biological basis by which the most recurrent endometrial carcinoma-specific mutation site P179 facilitates features of endometrial carcinoma malignancy has yet to be fully determined. Here, we used a series of structural, biochemical, and biological approaches to investigate the impact of the P179R missense mutation on PP2A function. Enhanced sampling molecular dynamics simulations showed that arginine-to-proline substitution at the P179 residue changes the protein's stable conformation profile. A crystal structure of the tumor-derived PP2A mutant revealed marked changes in A-subunit conformation. Binding to the PP2A catalytic subunit was significantly impaired, disrupting holoenzyme formation and enzymatic activity. Cancer cells were dependent on PP2A disruption for sustained tumorigenic potential, and restoration of wild-type Aα in a patient-derived P179R-mutant cell line restored enzyme function and significantly attenuated tumorigenesis and metastasis in vivo. Furthermore, small molecule-mediated therapeutic reactivation of PP2A significantly inhibited tumorigenicity in vivo. These outcomes implicate PP2A functional inactivation as a critical component of high-grade endometrial carcinoma disease pathogenesis. Moreover, they highlight PP2A reactivation as a potential therapeutic strategy for patients who harbor P179R PPP2R1A mutations. SIGNIFICANCE: This study characterizes a highly recurrent, disease-specific PP2A PPP2R1A mutation as a driver of endometrial carcinoma and a target for novel therapeutic development.See related commentary by Haines and Huang, p. 4009.
Trainee GP is given written warning for faking antibiotic prescription to treat herself
Authors: Clare Dyer
Journal: BMJ (2019)

A trainee general practitioner who faked a prescription for antibiotics from another doctor to treat her own “embarrassing medical condition” has been given a written warning by a medical practitioners tribunal.

Ashleigh Williams, 28, wrote another doctor’s name on the top of a prescription for amoxicillin, even though she had already signed her own name at the bottom. She then presented it at the outpatient pharmacy of Burnley General Hospital, where she works.

But a suspicious pharmacist told her that she had called the doctor named on the prescription, who denied writing it. Williams then spoke to the doctor on the phone from the pharmacy, claiming that the prescription was for her younger sister, who …
The role of proinflammatory immune (IFN-gamma) gene signature in predicting prognosis and response to chemotherapy in uterine carcinoma.
Authors: Haider Mahdi, Peter Graham Rose, Fadi W Abdul-Karim, Bradley J. Monk, Ying Ni
Journal: Journal of Clinical Oncology (2019)

e14209 Background: Immunotherapy is promising option given low toxicity and potential durable response. In mismatch repair proficient endometrial and ovarian cancers, the reported response rate is ranging from 10-15% in recurrent setting. We need to better identify subset of patients who benefits from immunotherapy. Multigene immune signatures represent a robust means of capturing a complex, T cell–inflamed phenotype necessary for the clinical activity of PD-1–/PD-L1–directed monoclonal antibodies. IFN-γ is a key cytokine produced by activated T cells, as well as natural killer (NK) and NK T cells, in the tumor microenvironment. An immune-related IFN-γ 18-gene profile was derived through a cross-validated penalized regression modeling strategy to predict response to anti-PD1 therapy across 9 different tumor types. We want to test if this gene panel can also predict cancer outcome and response to chemotherapy. Methods: We used whole transcriptome sequencing of RNA matched tumor-normal samples from 38 high stage (Stage III and IV) uterine serous cancer patients. All patients received chemotherapy with platinum and taxanes. IFN-18 gene expression score was calculated by averaging the normalized and log transformed individual gene read counts. The optimized score cut off was selected to best separating the progression free survival. Then the cut off score was tested in The Cancer Genomic Atlas (TCGA) uterine and ovarian cancer RNAseq datasets. Results: The IFN score of 2.46 was determined based on 18-gene expression derived from 38 high-stage uterine serous cancer samples. Average age was 67 years (range: 56-82 years). Uterine serous cancer is known to be MSI stable. Patients with score higher than 2.46 showed significantly longer progression free survival (PFS – 57.6 months vs 15months, p = 0.002) and longer overall survival (73.1 months vs 51.1 months), not statistically significant given our small sample size, p = 0.13) compared to the patients with score lower than 2.46. Then this IFN based gene signature was then applied to TCGA 541 uterine cancer samples with RNAseq data. Similarly, this signature predicted significant improvement in both progression-free survival (p = 0.001) and overall survival (p = 0.005). Interestingly, this score cannot separate outcome for TCGA ovarian cancer cohort. Conclusions: Immune-related IFN-γ gene signature predicted prognosis and response to chemotherapy. We plan to assess if this signature will predict endometrial cancer patients who benefits from anti-PD1 therapy.
Annual lung cancer screening by chest x-ray results in higher profits for the exclusion of lung cancer.
Authors: Tatsuo Kimura, Shinya Fukumoto, Hiroyasu Morikawa, Akemi Nakano, Koji Otani, Yukie Tauchi, Risa Uemura, Tomohiro Suzumura, Koichi Ogawa, Tomoya Kawaguchi, Norifumi Kawada
Journal: Journal of Clinical Oncology (2019)

e23050 Background: Chest X ray (CXR) has been the most common screen procedure for detection of lung cancer. However, if patients had old inflammatory shadows such as tuberculosis, calcification and fibrotic changes, it would become increasingly difficult to detect the lung cancer. In that case, the previous CXR helps the detection of new shadows. We examine whether the repeat participants (pts) who received the medical checkup annually, may improve the rate of lung cancer detection. Methods: Our clinic “MedCity21” was a university outpatient clinic to undergo a complete medical checkup in private health screening program. The pts with abnormalities detected in CXR were announced by call request and invited to our specialty clinic for chest CT scan as further examination. We examined the varieties of abnormal shadows by CXR and CT scans in recent 3 years. Furthermore, we compared the differences between the repeat and the first-time pts using the chi-square tests. Results: In 2016, 2017 and 2018, a total of 10020, 11925 and 12540 pts were enrolled, respectively. The CXR abnormalities for further examinations were detected in 282 (2.8%), 344 (2.9%) and 335 (2.6%) pts, respectively. After the call requests, 203 (72.0%), 239 (69.4%) and 239 (71.3%) pts received chest CT scan in our clinic. In 2016 and 2017, 7 and 9 pts were diagnosed as lung cancer within 12 months follow-up. In 2018, 6 pts were diagnosed as lung cancer, and another 4 pts were now observed. The numbers of lung cancer detections by CXR per 100,000 people were 70.0, 75.5 and ≥47.8, respectively. The repeat / first time pts in 2018 were 6898/5642 pts (55/45%), and 142/193 pts (2.1/3.4%) had CXR abnormalities (p &lt; 0.01), respectively. The varieties of abnormal shadows by CT scans showed that 8.3/20.8% of old inflammatory shadows (p &lt; 0.01), 11.9/20.7% of nodule or GGO (p = 0.47), 12.8/12.3% of Mycobacterial infections or suspected (p = 0.46), and 11.0/6.9% of acute bacterial infections (p = 0.98). Lung cancer was detected in 3/3 pts (p = 0.86), respectively. Conclusions: The repeat pts had significantly lower rate of CXR abnormalities detection, and the first time pts had higher rate of error detection old inflammatory changes as significant. In private health screening program, the repeat pts may have higher profits for the exclusion of lung cancer than the first time pts.