tbuckley/cabot-search huggingface dataset:
Evaluation of the clinical utility of kallikrein-related peptidase 6 gene (<i>KLK6</i>) downregulation in breast cancer.
Authors: Kleita Michaelidou, Alexandros Tzovaras, Nikolaos Tsoukalas, Konstantinos Mavridis, Grecory Tsoukalas, Nikos Tsapralis, Sofia Stamatopoulou, Dimosthenis Zylis, Ioannis Misitzis, Alexandros Ardavanis, Andreas Scorilas
Journal: Journal of Clinical Oncology (2012)

10606 Background: Breast cancer (BC), the most common malignancy among the female population, remains a crucial public health problem. The identification and exploitation of novel molecular biomarkers can contribute in the multidimensional approach which is required for optimal management of BC patients. The abnormal expression of several KLK members has been documented for breast cancer. Interestingly, many of these genes are found to be potential prognostic markers for this malignancy. KLK6 expression is positively associated with tumor progression in various human malignancies; however in breast cancer, it can restrain tumor progression. We therefore sought to investigate the possible clinical value of KLK6 as a breast cancer biomarker. Methods: Total RNA was isolated from 107 breast tumors and their matched normal compartments. After testing the quality of the extracted RNA, cDNA was prepared by reverse transcription. Quantitative Real-time PCR was performed, for KLK6 mRNA quantification, using the SYBR Green chemistry. Relative quantification analysis was made using the comparative Ct (2 -ΔΔC T ) method. HPRT1 was used as an endogenous control gene and BT-474 breast cancer cell line served as a calibrator. Results: KLK6 mRNA levels were significantly downregulated in the cancerous breast tissue specimens compared to their normal counterparts (p&lt;0.001). Additionally, a negative association was observed between KLK6 expression status and tumor stage, given the fact that 54.2% of less advanced breast tumors (TNM stage≤ T2a) were KLK6-positive compared to the 34.6% of more advanced-stage tumors (TNM &gt;T2a) (p=0.034). Moreover, a statistically significant negative correlation was documented between KLK6 mRNA levels and estrogen (p&lt;0.001) and progesterone receptor (p=0.003) statuses. Conclusions: The downregulation of KLK6 in cancerous compared to normal sections of breast tissue samples reflects the reported tumor suppressor properties of KLK6 gene in breast malignancies. Furthermore, the negative association of KLK6 mRNA expression with tumor stage, ER and PR statuses reveals the putative role of KLK6 as a promising prognostic breast cancer biomarker.
LACK OF ASSOCIATION OF MITRAL VALVE GRADIENT AFTER MITRACLIP WITH OUTCOMES IN FUNCTIONAL MITRAL REGURGITATION: RESULTS FROM THE COAPT TRIAL
Authors: Rim Halaby, Howard Herrmann, Scott Lim, Saibal Kar, None Kar, JoAnn Lindenfeld, William Abraham, Paul A. Grayburn, Federico M. Asch, Neil J. Weissman, Yiran Zhang, Michael Mack, Gregg Stone
Journal: Journal of the American College of Cardiology (2020)
Covid-19: GPs call for appraisals and CQC inspections to be suspended
Authors: Abi Rimmer
Journal: BMJ (2020)

GP leaders have called for assurances that they will not face contractional sanctions if a covid-19 pandemic forces them to suspend normal practice.

Delegates attending a special conference of local medical committees, held in London on 11 March, unanimously voted in favour of a motion that called on the BMA’s General Practitioners Committee in England to negotiate changes to protect practices in the event of a covid-19 pandemic.

The motion called for funding from the quality and outcomes framework (QOF) and directed enhanced services to be used to fund essential services and for any additional costs accrued by practices related to covid-19 infections to be reimbursed. It said that practices should be able to “prioritise frontline work and suspend other requirements including …
Estimating long-term efficacy of multi-catheter brachytherapy in Japanese breast cancer patients.
Authors: Kazuhiko Sato, Yoshio Mizuno, Takahiro Shimo, Masahiro Kato
Journal: Journal of Clinical Oncology (2013)

e12009 Background: The efficacy of an accelerated partial breast irradiation (APBI) has been investigated as an alternative method to whole breast irradiation (WBI) in breast-conserving treatment (BCT). We have previously reported that multi-catheter brachytherapy as APBI using intra-operative open-cavity implant (IOCI) technique is feasible for Japanese patients. Since the follow-up period of this technique was relatively short, a long-term efficacy has been evaluated using an individualized-case-control (ICC) analysis. Methods: 179 consequent patients with 183 lesions were treated with BCT using IOCI from October 2008 to January 2013. Patients with bilateral breast cancer were included in the database twice. After the confirmation of the free margin and negative sentinel-nodes for metastases using frozen section analysis, applicators were inserted. APBI was started the same day of the operation, delivering 32 Gy in 8 fractions. We performed an ICC analysis to estimate the number of patients with an ipsilateral breast recurrence (ILBR). The 10-year risk of ILBR for each patient if treated by BCT with WBI was calculated with web-based decision-making tool (IBTR!) and it was adjusted by the actual follow-up period using EBCTCG overview’s data. Results: 123 patients with pN0 and longer than 1 year follow-up were enrolled in this analysis. Their mean age was 54.9 years. Most tumors (94.3%) were 2 cm or less in diameter. The median follow-up period was 3.0 years (1.0-4.3 years). All toxicities related to radiation therapy were mild. When BCT was performed with and without WBI, we estimated that there should be 1.2-2.4 and 4.9-9.1 ILBR in this group, respectively. Although one ILBR was observed, there was no tumor-bed recurrence in this treatment group. Conclusions: There was only one ILBR (no tumor-bed recurrence), which was within an estimated range of local recurrences. Multi-catheter brachytherapy using this technique is expected to offer the same rates of long-term local control than WBI using ICC analysis.
Variability of gene expression profile in breast cancer core biopsy: Impact on prognostic and predictive multigene signatures.
Authors: Michal Jarzab, Wieslaw Bal, Malgorzata Kowalska, Malgorzata Oczko-Wojciechowska, Monika Kowal, Justyna Rembak-Szynkiewicz, Alicja Dyla, Ewa Chmielik, Ewa Stobiecka, Barbara Bobek-Billewicz, Rafal Tarnawski
Journal: Journal of Clinical Oncology (2012)

e21049 Background: Gene expression profiling has been shown to be effective in the analysis of postoperative tumor samples in breast cancer. However, when small specimens like core biopsy samples are considered, the small size of the collected material makes it difficult to obtain high tumor percentage in the specimen. Thus, we tested the strategy of obtaining three independent cores for molecular analysis and assessed the influence of the stability of different prognostic and predictive signatures. Methods: We prospectively collected breast core biopsies from 82 consecutive patients treated by pre-operative chemotherapy. In each patient, three cores from different tumor areas were sampled for molecular testing, independent of the cores collected for histopathological analysis. RNA was isolated by QIAGEN RNeasy kits, gene expression profiling was carried out using Affymetrix HG-U133 Plus 2.0 microarrays. Results: In 27 patients, three independent specimens were analyzed by microarray gene expression profiling (in total 81 samples). When this training set was analyzed by unsupervised Principal Component Analysis, the overall concordance between the three tumor cores was observed, but no such concordance was seen for three tumors (for each with one significant outlier). When we assessed the set of chosen 20 prognostic and predictive signatures, we confirmed that the homogeneity of gene expression within the signatures is significantly better than for random sets of genes, but we observed the notable differences between the signatures. The heterogeneity decreased when genes with low between-patient variance were excluded; they also showed a higher intra-patient variability of gene expression. We also assessed the heterogeneity of single expression markers and furher validated our findings on an independent set of 55 patients. Conclusions: The use of three independent cores for gene expression testing in breast cancer may be a successful strategy to overcome tumor heterogeneity and sampling error and result in more stable results of prognostic and/or predictive signatures. Supported by Polish National Science Center grant N402 6861 40
RENIN-ANGIOTENSIN SYSTEM AND BETA BLOCKERS IN PREVENTION OF ANTHRACYCLINE CARDIOTOXICITY: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Monica Avila, Suellen Siqueira, Lucas Waldeck, Silvia M. Ayub-Ferreira, Richard Takx, Marcio Bittencourt, Edimar Alcides Bocchi
Journal: Journal of the American College of Cardiology (2020)
A phase I study of S-1 plus weekly docetaxel in patients with metastatic gastric cancer
Authors: S. R. Park, M. S. Yu, C. G. Kim, I. J. Choi, J. S. Lee, Y. W. Kim, K. W. Ryu, J. H. Lee, J. M. Bae, H. K. Kim
Journal: Journal of Clinical Oncology (2006)

14005 Background: We conducted a study to define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of S-1 plus weekly docetaxel in pts with metastatic gastric cancer (MGC), and to recommend a dose for phase II study Methods: Pts with MGC, age ≥ 18 yrs, ECOG PS 0–2, adequate organ function, and no or 1–2 prior chemotherapy were eligible. S-1 was given twice daily, p.o. on D1–14 and docetaxel i.v. on D1, 8, q 3 wks. Each cohort of 3 pts was treated with escalating doses of S-1/docetaxel at 60/25 (level I), 70/25 (level II), 70/30 (level III), 80/30 (level IV), 80/35 (level V), 90/35 (level VI), and 90/40 mg/m 2 (level VII). The DLT pertaining to 1st cycle only was obtained. Results: Thirty pts with median age of 50 yrs (range: 27–71) with MGC received a median of 8 cycles (range: 1–12). A total of 222 cycles were administered. DLTs were; G3 elevated liver enzyme at level I (1/6 pts), gastric perforation at level V (1/6), G3 diarrhea and febrile neutropenia (FN) with G3 nausea/anorexia/fatigue at level VI (2/6), and FN and neutropenic infection (NI) with G3 stomatitis at level VII (2/3). After DLT occurred in 2 of 3 pts in level VII, 2 of additional 3 pts enrolled at level VI had DLT. Then, 1 pt developed DLT among additional 3 pts enrolled at level V. Therefore, MTD and recommended dose (RD) were level VI and V, respectively. There were 2 CRs, 17 PRs with response rate of 65.5% (95% CI 48.2–82.8%), 8 SDs and 2 PDs among 29 efficacy-evaluable pts. Conclusions: MTD for this regimen was S-1 90 mg/m 2 /d + docetaxel 35 mg/m 2 and RD was S-1 80 mg/m 2 /d (D1–14) + docetaxel 35 mg/m 2 (D1, 8). (Supported by National Cancer Center Grant; Docetaxel and S-1 were provided by Sanofi-Aventis Korea and Jeil Pharm. Co., respectively) [Table: see text] No significant financial relationships to disclose.
THE ASSOCIATION BETWEEN HEART FAILURE AND INCIDENT CANCER IN WOMEN: AN ANALYSIS OF THE WOMEN'S HEALTH INITIATIVE
Authors: Douglas Leedy, Kerryn Reding, Alexi L. Vasbinder, Garnet Anderson, Aladdin H. Shadyab, Ana Barac, Wayne Levy, Jean Wactawski-Wende, LiHong Qi, Richard Kar-Hang Cheng
Journal: Journal of the American College of Cardiology (2020)
ASSOCIATION OF BODY MASS INDEX AND OUTCOMES AFTER TRANSCATHETER MITRAL VALVE REPAIR
Authors: Sameer Arora, Zhuokai Li, Sreekanth Vemulapalli, Pedro Villablanca, Arman Qamar, Andrzej Kosinski, Taku Inohara, Matthew Aaron Cavender, John Vavalle
Journal: Journal of the American College of Cardiology (2020)
OUTCOMES OF CHRONIC TOTAL OCCLUSION PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH PRIOR CORONARY ARTERY BYPASS GRAFT SURGERY
Authors: Michael Megaly, Bishoy Abraham, Mohamed Omer, Ayman Elbadawi, Marwan Saad, Amgad Mentias, Iosif Xenogiannis, Mahesh Anantha Narayanan, Subhash Banerjee, Khaldoon Alaswad, Stéphane Rinfret, Santiago Garcia, Ashish Pershad, Lorenzo Azzalini, Paul Knaapen, Etsuo Tsuchikane, Anthony Gershlick, M. Nicholas Burke, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2020)
Comparison of two multimarker serum tests for the prediction of ovarian cancer in women with a pelvic mass.
Authors: David G. Grenache, Zivjena Vucetic
Journal: Journal of Clinical Oncology (2013)

5555 Background: Distinguishing between benign and malignant disease in women with a pelvic mass is difficult. OVA1 and ROMA are two multi-marker serum tests that are FDA-cleared to assess risk of malignancy in individuals with a pelvic mass. This study compared the accuracy of these tests for the prediction of ovarian cancer (OCa) in women with a pelvic mass. Methods: OVA1 and ROMA risk scores were determined in a subset of 146 serum samples obtained prospectively from pelvic mass patients. Patients were categorized by an initial cancer risk assessment (ICRA) performed by a physician and true cancer status determined surgically. 31 patients with malignancy (6 with a benign ICRA) and 115 patients with benign disease (25 with a malignant ICRA) were evaluated. Quest Diagnostics performed the OVA1 tests (CA-125, prealbumin, apolipoprotein A-1, β2-microglobulin, transferrin) and calculated and interpreted the risk score. ROMA tests (CA-125 and HE-4) were determined by automated immunoassay using an Abbott Architect analyzer. ROMA risk scores were calculated using published formulas and interpreted against cutpoints previously established for automated CA-125 and HE-4 performed by manual ELISA. Results: There were 70 pre- and 76 post-menopausal subjects. Of the 31 with malignancy, 26 had OCa (54% &gt;stage II), 5 with an ICRA of benign. ROC curve analysis of the entire cohort produced an AUC of 0.88 (95% CI 0.80-0.95) and 0.93 (95% CI 0.87-0.99) for OVA1 and ROMA, respectively. OVA1 had a sensitivity of 0.97 and a specificity of 0.55. ROMA had a sensitivity of 0.84 and a specificity of 0.83. The sensitivity of OVA1 for OCa in the ICRA benign cohort (N = 5) was 0.80 and for ROMA was 0.40. The respective specificity for benign disease in this cohort (N=90) was 0.64 and 0.90. The sensitivity of ROMA for OCa increased to 0.60 with a slight decrease in specificity (0.87) when a cutpoint determined by ROC curve analysis was used. Conclusions: Overall, OVA1 and ROMA have similar performance characteristics. In women with an ICRA of benign, OVA1 was more sensitive among those who had OCa but ROMA was more specific among those who did not. The use of a ROMA cutpoint specific for the combination of automated CA-125 and HE-4 tests improved sensitivity.
PRECISION MEDICINE OPPORTUNITIES FOR FAMILIAL ARRHYTHMIAS AND CARDIOMYOPATHIES IDENTIFIED WHEN COST OF GENETIC TESTING IS REMOVED AS A BARRIER
Authors: Thomas E. Callis, Rebecca Truty, Edward D. Esplin, Ana Morales, John Garcia, Matteo Vatta, Robert L. Nussbaum
Journal: Journal of the American College of Cardiology (2020)
REFRACTORY CARDIOGENIC SHOCK DUE TO ARRHYTHMOGENIC CARDIOMYOPATHY IN THE SETTING OF A RAPIDLY PROGRESSIVE SCLERODERMA-DERMATOMYOSITIS OVERLAP SYNDROME
Authors: Gregory T. Marecki, Leonid Garber, Xingchen Mai, Navneet Narula, Randal I. Goldberg, Stuart Katz, Claudia G. Gidea, Kazuhiro Hisamoto, Nader Moazami, Deane Smith, Nathaniel Smilowitz, Carlos L. Alviar
Journal: Journal of the American College of Cardiology (2020)
Novel pleural-bladder pump in malignant pleural effusions: from animal model to man
Authors: Philippe Astoul, Sophie Laroumagne, Jeroen Capel, Nicholas A Maskell
Journal: Thorax (2020)

Malignant pleural effusion is common and causes disabling symptoms such as breathlessness. Treatments are palliative and centred around improving symptoms and quality of life but an optimal management strategy is yet to be universally agreed. A novel pump system, allowing fluid to be moved from the pleural space to the urinary bladder, may have a role for the management of recurrent malignant pleural effusion. We hereby describe the first animal study using this device and the results of the first application in patients.
Pregnancy outcome in chronic myeloid leukemia patients on imatinib therapy.
Authors: Swati Dasgupta, Ashis Mukhopadhyay, Ujjal Kanti Ray, Firoj Hossain Gharami, Chinmay Kumar Basu, Soma Mukhopadhyay
Journal: Journal of Clinical Oncology (2013)

7114 Background: Now that imatinib is being used to treat thousands of chronic myeloid leukemia (CML) patients for more than 10 year it is highly probable that many patients will get pregnant during its use. Company warns against any such use. But the fact remains that there is need for planned pregnancies in indicated cases. So we selected few cases both male and female for such pregnancies by interrupting treatment and following the pregnancy closely. Their outcome was studied so that we have an idea about what best could be suggested in such instance. Methods: From November 2002 to May 2010, 634 patients with CML in any stage of the disease were treated with imatinib at our tertiary cancer research institute. We selected 22 (12 females and 10 males) cases of pregnancies by interrupting treatment. We reported 9 accidental pregnancies and 13 planned pregnancies involving 22 patients who or their wives conceived while receiving imatinib for the treatment of CML. Results: Among 22 pregnancies there were 3 spontaneous abortions and 4 elective abortions. In case of 7 female patients, 3 and 4 were male and female babies respectably and in case of six male patients 4 and 4 were male and female babies. Two babies were with congenital anomaly such as one Hypospandium and one Mild-Hydrocephalus (in case of unplanned pregnancies and imatinib exposure during the first trimester of organogenesis). Conclusions: In conclusion, exposure to Imatinib during pregnancy might result in an increased risk of serious fetal abnormalities or spontaneous abortions. Women of childbearing potential should use adequate contraception while using Imatinib. We can suggest that planned pregnancy during therapy should be encouraged but imatinib therapy in unplanned pregnancy can cause spontaneous abortion or minor congenital anomaly.
THE PREVALENCE OF VALVULAR HEART DISEASE IN PERSONS LIVING WITH HIV: A MIAMI HEALTH SYSTEM RETROSPECTIVE ANALYSIS
Authors: Jelani Kayode Grant, Louis Vincent, Bertrand Ebner, Fahim Payarali, Alexander Toirac, Kunal Kapoor, Gerardo Zablah, Johnny Galli, Alexis Powell, Catherine Boulanger, Dushyantha Jayaweera, Michael Kolber, Barry Hurwitz, Claudia A. Martinez
Journal: Journal of the American College of Cardiology (2020)
A randomized, double blind, placebo-controlled crossover trial of a sustained release methylphenidate in cancer-related fatigue.
Authors: Carmelita P. Escalante, Christina A. Meyers, James M. Reuben, Xuemei Wang, Wei Qiao, Ellen F. Manzullo, Ricardo H. Alvarez, Phuong Khanh H. Morrow, Ana M. Gonzalez-Angulo, Tito R. Mendoza, Xin Shelley Wang, Wenli Liu, Holly Michelle Holmes, Jessica Hwang, Katherine Pisters, Michael J. Overman, Charles S. Cleeland
Journal: Journal of Clinical Oncology (2012)

9072 Background: Cancer-related fatigue (CRF) is common and distressing. This study assessed the efficacy of OROS methylphenidate 18 mg daily (OM) vs. placebo (P) for CRF reduction. Other objectives were to compare the effects of OM vs. P on other symptoms, cognitive function, work yield, patient (pt) perceptions and preferences, and an exploratory analysis of cytokines. Methods: Initially, pts were randomly assigned (1:1) to receive OM-P or P-OM for 4 weeks (wks). Pts were crossed to the other treatment after 2 wks. Assessments were done at baseline, 2 and 4 wks. Continuous and categorical variables were assessed using Wilcoxon signed rank tests and McNemar tests, respectively. The primary efficacy end point was the change of “fatigue worst” on the Brief Fatigue Inventory (BFI) at the end of each 2 wk period. Results: 42 female breast cancer pts were enrolled (3 ineligible, 6 unevaluable); 33 pts were studied. The mean age was 58 (range, 32-79), 30% had metastasis, 82% were receiving chemotherapy (ctx), 9% hormonal therapy (ht), and 9% both ctx and ht. 94% were ECOG &lt;1 and 52% were employed. 45% were on pain medicines and none on antidepressants. The mean baseline BFI was 5.7 (range 4.1-8.6). Fatigue worst did not differ between OM and P (p= 0.54) or in other symptoms. There was significance in WAIS-III Digit Symbol between OM and P (p=0.01), and Hopkins Verbal Learning Test with BFI interfere and BFI active (p=0.04, p=0.03, respectively). Hours (hrs) missed due to health (p=0.03) and hrs worked (p=0.04) differed in OM vs. P. At study end, pts were asked if OM improved CRF and if they wanted to stay on OM. 64% felt improved. Of these, 58% wanted to continue. There were no serious adverse events due to OM. There were differences in serum IL6 (p=0.03), IL10 (p=0.0004), and TNFα (p=0.02) among OM and P. Conclusions: Low dose OM did not show improvement in CRF on fatigue worst of BFI. Pts taking OM had better cognition and less work absences. Pts tolerated OM well and a majority felt better and wanted to continue OM. Future studies examining higher doses or longer treatment duration with OM, pt preferences and impact on productivity are necessary. Changes in serum cytokine levels should be further explored.
CONSCIOUS SEDATION VERSUS GENERAL ANESTHESIA FOR TRANSCATHETER AORTIC VALVE REPLACEMENT: RESULTS OF AN INSTRUMENTAL VARIABLE ANALYSIS
Authors: Neel Butala, Mabel Chung, Eric Secemsky, Pratik Manandhar, Guillaume Marquis-Gravel, Andrzej Kosinski, Sreekanth Vemulapalli, Robert W. Yeh, David J. Cohen
Journal: Journal of the American College of Cardiology (2020)
ZERO CONTRAST APPROACH FOR MANAGEMENT OF SEVERE IN-STENT RESTENOSIS USING INTRAVASCULAR ULTRASOUND GUIDED LASER ATHERECTOMY AND BRACHYTHERAPY IN A PATIENT WITH CONTRAST INDUCED NEPHROPATHY
Authors: Joe Aoun, Apurva Patel, Isaac Tea, Hasan Rehman, Alpesh Shah
Journal: Journal of the American College of Cardiology (2020)