tbuckley/cabot-search huggingface dataset:
Incretin based treatments and mortality in patients with type 2 diabetes: systematic review and meta-analysis
Authors: Jiali Liu, Ling Li, Ke Deng, Chang Xu, Jason W Busse, Per Olav Vandvik, Sheyu Li, Gordon H Guyatt, Xin Sun
Journal: BMJ (2017)

To assess the impact of incretin based treatment on all cause mortality in patients with type 2 diabetes.
Long term follow up (LTFU) of adjuvant zoledronic acid (ZOL) in high risk early stage breast cancer (ESBC) defined by bone marrow (BM) disseminated tumor cells (DTC).
Authors: Neelima Vidula, Jimmy Hwang, Sally Greenberg, Michelle E. Melisko, Andrei Goga, Mark Moasser, Ariadna Gasol Cudos, Austin Nicholas Angelidakis, Amy DeLuca, Laura A Petrillo, Mark Jesus Mendoza Magbanua, John Park, Hope S. Rugo
Journal: Journal of Clinical Oncology (2017)

e12001 Background: BM DTC &amp; peripheral blood CTC indicate metastatic potential. Adjuvant bisphosphonates in postmenopausal patients (pts) result in less bone metastases and better survival. We studied ZOL’s impact on DTC, CTC, and outcomes in ESBC (ASCO, 2010) and now report updated LTFU. Methods: Forty-five pts with ESBC and DTC &gt; 4/mL BM were given ZOL every 4 weeks for 24 months (mo). DTC were quantified at baseline (BL), 12 and 24 mo of ZOL with immunomagnetic enrichment and flow cytometry (Clin Cancer Res, 2015). Serial CTC, survival, recurrence and toxicity were studied. Results: Forty-five pts received ZOL (56% HR+, 18% HER2+, 40% TN, 96% prior chemo). BL median DTC was 13.3/mL (range 4-333). Median DTC decreased from BL to 12 mo (median reduction 6.5/mL, range -57.2 to 23.6) and from BL to 24 mo (median reduction 4.6/mL, range -43.1 to 160.1). For 33 pts with BM at all 3 times, DTC decreased: BL median 11.5/mL (range 4-59.3), 12 mo median 6.8/mL (range 0-28.5), 24 mo median 6.5/mL (range 0.3-168.6). At 12 &amp; 24 mo, 32% &amp; 26% had undetectable DTC respectively. Median CTC was 0.2/mL at BL (n = 45), 0.25/mL at 6 mo (n = 30), 0/mL at 12 mo (n = 22) &amp; 0.2/mL at 24 mo (n = 23). At 123 mo median FU (range 5-154), 9 (20%) pts recurred. Median time to recurrence was 21 mo (range 6-105); 67 % (6/9) TN, 22% (2/9) ER+/HER2+. The first sites of recurrence were CNS in 33% (3), bone &amp; viscera in 22% (2), viscera in 22% (2) and local in 22% (2). BL DTC &gt; 30/mL was associated with higher recurrence (50% &gt; 30 vs. 14% &lt; 30, p = 0.039). All 3 pts with CNS disease had BL DTC &gt; 30/mL. Of the pts who recurred, 4 had ≥ 1 serial BMA; 2/4 had increasing DTC before recurrence. Of 32 disease free pts with BMA at all 3 times, 72% (23) had decreased DTC from BL to 24 mo. Of the 13.3% (6) pts who died, 67% (4) had BL DTC &gt; 30/mL, which was associated with a greater risk of death (50% &gt; 30 vs. 5% &lt; 30, p = 0.006). BL CTC &gt; 0.8/mL was associated with higher recurrence (60% &gt; 0.8 vs. 15% &lt; 0.8, p = 0.047) &amp; death (60% &gt; 0.8 vs. 8% &lt; 0.8, p = 0.013). ZOL was well tolerated. Conclusions: At 123 mo FU, BL DTC &gt; 30/mL and CTC &gt; 0.8/mL correlated with recurrence &amp; death. In this single arm phase II study, adjuvant ZOL decreased DTC over time, supporting the anti-tumor effect of bisphosphonates. Clinical trial information: NCT00295867.
Seasonal changes in cyclists' performance. Part II. The British Olympic track squad.
Authors: J. A. White, G. Quinn, M. Al-Dawalibi, J. Mulhall
Journal: British Journal of Sports Medicine (1982)

In Part II of the study, the British Olympic track (sprint) squad cyclists demonstrated reductions in body fat index, % body fat and endomorphy (p greater than .05), increased Hb and PCV % (p greater than .05), and lowered HR at rest and in warm-up exercise (p greater than .05), but no change in leg power. Repeated interval sprints of short duration, maximal exercise on an "ergowheel" ergometer, at standardised power output, showed increased anaerobic index (p greater than .05) and acceleratory power (p greater than .01) but no change in sustained power output. Compared with "non-select" riders, a case study of the single "select" rider showed anthropometric differences in terms of lower height, weight, body fat index, % body fat and endomorphy, but enhanced mesomorphy and FEV %. Furthermore, the "select" rider demonstrated temporarily latent functional performance capabilities, in that increased anaerobic index, acceleratory and sustained power indices, as well as enhanced relative power output, were not identified until late in the competitive season.
Eribulin in combination with pertuzumab plus trastuzumab for HER2-positive advanced or recurrent breast cancer (JBCRG-M03).
Authors: Kazutaka Narui, Toshinari Yamashita, Masahiro Kitada, Hidetoshi Kawaguchi, Masaya Hattori, Tetsuhiro Yoshinami, Nobuki Matsunami, Kazuhiro Yanagihara, Teru Kawasoe, Takeshi Nagashima, Hiroko Bando, Hiroshi Yano, Yoshie Hasegawa, Rikiya Nakamura, Masahiro Kashiwaba, Norikazu Masuda, Satoshi Morita, Shinji Ohno, Masakazu Toi
Journal: Journal of Clinical Oncology (2017)

1025 Background: Pertuzumab (P) provided overall and progression-free survival (PFS) benefits in HER2-positive metastatic breast cancer (MBC) in the CLEOPATRA study as a first-line therapy. However, long-term administration of intravenous docetaxel at a dose of 75 mg/m 2 every 3 weeks in MBC patients is difficult. Eribulin (E) is a well-tolerated cytotoxic agent. We report the efficacy and safety of E in combination with trastuzumab (T) plus P as first- and second-line therapy for metastatic or advanced BC in a multicenter, open-label phase II study (UMIN000012232). Methods: HER2-positive advanced or recurrent BC patients with no or a single prior therapy as advanced or recurrent chemotherapy were enrolled. All patients were administered T and taxane as adjuvant or first-line chemotherapy. Treatment consisted of E 1.4 mg/m 2 on days 1 and 8 of a 21-day cycle and T (8 mg/kg loading dose &gt; 6 mg/kg) plus P (840 mg loading dose &gt; 420 mg) once every 3 weeks, all given intravenously. The primary end point was PFS. Results: From November 2013 to April 2016, 50 patients were enrolled. Forty-nine patients were eligible for safety analysis; full analysis set (FAS) includes 46 patients. The median patient age was 56 years (range 23–70), and 8 (16%) and 41 (84%) patients were treated in first- and second-line settings, respectively. Twenty-eight patients out of 49 patients (57%) continued the protocol therapy at the end of 8 cycles and median PFS was not yet reached. The response rate by RECIST ver.1.1 was 56.5% in FAS. The relative dose intensity of E, T, and P were 93.3% (range 77.0%–100%), 100% (range 96.0%–100%) and 100% (range 89.7%–100%), respectively in FAS. The grade 3/4 adverse effects (AE) were neutropenia in 5 patients (10.2%) including 2 patients (4.1%) with febrile neutropenia, hypertension in 3 patients (6.1%), and other AEs in only one patient. Average of the ejection fraction did not decrease significantly. Symptomatic left ventricular systolic dysfunction was not observed. Conclusions: E in combination with T plus P was well-tolerated and could be an alternative to docetaxel-based combination therapy for HER2-positive MBC. Clinical trial information: 000012232.
Remission of Hematuria Improves Renal Survival in IgA Nephropathy
Authors: Angel M. Sevillano, Eduardo Gutiérrez, Claudia Yuste, Teresa Cavero, Evangelina Mérida, Paola Rodríguez, Ana García, Enrique Morales, Cristina Fernández, Miguel Angel Martínez, Juan Antonio Moreno, Manuel Praga
Journal: Journal of the American Society of Nephrology (2017)

Hematuria is a cardinal symptom in IgA nephropathy, but its influence on the risk of disease progression has been scarcely investigated. We followed a cohort of 112 patients with IgA nephropathy for a mean±SEM period of 14±10.2 years, during which clinical and analytic risk factors (including urine sediment examination) were regularly recorded. According to the magnitude of time-averaged hematuria, we classified patients as those with persistent hematuria and those with negative or minimal hematuria. We also classified patients according to the magnitude of time-averaged proteinuria (>0.75 or ≤0.75 g/d). The proportion of patients reaching ESRD or a 50% reduction of renal function was significantly greater among patients with persistent hematuria than patients with minimal or negative hematuria (30.4% and 37.0% versus 10.6% and 15.2%, respectively; P=0.01). Multivariable analysis revealed time-averaged hematuria, time-averaged proteinuria, renal function at baseline, and the presence of tubulointerstitial fibrosis on renal biopsy as independent predictors of ESRD. After hematuria disappearance, which occurred in 46% of the patients, the rate of renal function decline changed from -6.45±14.66 to -0.18±2.56 ml/min per 1.73 m2 per year (P=0.001). Patients with time-averaged proteinuria >0.75 g/d had significantly poorer renal survival than those with time-averaged proteinuria ≤0.75 g/d. However, on further classification by time-averaged hematuria, only those patients with time-averaged proteinuria >0.75 g/d and persistent hematuria had significantly worse renal survival than those in the other three groups. In conclusion, remission of hematuria may have a significant favorable effect on IgA nephropathy outcomes.
Environmental Exposures to Lead, Mercury, and Cadmium and Hearing Loss in Adults and Adolescents: KNHANES 2010–2012
Authors: Yoon-Hyeong Choi, Sung Kyun Park
Journal: Environmental Health Perspectives (2017)

The prevalence of hearing loss increases rapidly with aging. Hearing loss is common in all age groups, even in young adults and adolescents. A growing body of evidence has suggested that heavy metals have ototoxic effects, yet few epidemiological studies have investigated the association between heavy metals and hearing loss in a general population that includes adults and adolescents.We examined the association between environmental exposures to lead, mercury, and cadmium and the risk of hearing loss in adults and adolescents while controlling for potential confounding factors, including noise exposures and clinical factors.We analyzed cross-sectional data from 5,187 adults and 853 adolescents in the Korean National Health and Nutrition Examination Survey 2010-2012. Pure-tone average (PTA) of hearing thresholds at high frequency (3, 4, and 6 kHz) were computed, and hearing loss was defined as a PTA>25 dB in adults and PTA>15 dB in adolescents.In adults, the highest (vs. lowest) quartiles of blood lead and cadmium were associated with 1.70 (95% CI: 1.25, 2.31) and 1.47 (95% CI: 1.05, 2.05) odds ratios for high-frequency hearing loss (p-trend<0.001 and=0.007), respectively. In adolescents, the highest quartile (vs. lowest) of blood cadmium had an odds ratio of 3.03 (95% CI: 1.44, 6.40) for high-frequency hearing loss (p-trend=0.003), but blood lead was not associated with hearing loss. No significant association between blood mercury and hearing loss was suggested in either adults or adolescents.The results of the present study suggest that exposure to environmental lead and cadmium in adults and exposure to environmental cadmium in adolescents may play a role in the risk of hearing loss. https://doi.org/10.1289/EHP565.
Outcome of marked tumor marker increase in patients with advanced gastric cancer during chemotherapy without progression.
Authors: Keisho Chin, Mariko Ogura, Eiji Shinozaki, Mitsukuni Suenaga, Masato Ozaka, Takashi Ichimura, Takeru Wakatsuki, TOMOHIRO MATSUSHIMA, Nobuyuki Mizunuma
Journal: Journal of Clinical Oncology (2015)

e15034 Background: In case of marked tumor marker (TM) increase during chemotherapy (CTx) for advanced gastric cancer, sometimes we hesitate to continue the chemotherapy and few paper has been reported about the problem. Methods: In case of marked tumor marker (TM) increase during chemotherapy (CTx) for advanced gastric cancer, sometimes we hesitate to continue the chemotherapy and few paper has been reported about the problem. Results: Patient characteristics; Age median 69(37-89), Male 17/ Female 8, PS0/1/2 = 16/8/1,diffuse type histology 18/Intestinal type histology 6, Type3 or 4 gross type 17/other 8, 8 with target lesion (TL)/ without TL 17, 21 with evaluable lesion/4 no evaluable lesion, 1st/2nd /3rdline CTx = 21/3/1, 2xincreased TM; CEA/ CA19-9/CA125 = 8/15/2. PFS from 2xTM was 104days (median) and 3months PFS rate 64%. In 6 cases TM decreased to half without change the treatment after 2xTM increase. In 16 cases TM increased to 4 times of minimum. PFS from 4xTM was 55days (median) and 3months PFS rate 25%. Site of PD was 10 peritoneum metastasis, 4 local recurrence lesion, 4 gastric primary, 4 liver tumor and 2 ovary and uterus metastasis. Although we considered to be possible to do next line chemotherapy in 24(96%) patients at the 2xTM, it was not administered in 7 patients finally. In 11(44%), hospitalization for palliation or ascites drainage were needed within 1 months after PD and it is more frequent in patients without TL (P = 0.04, Fisher's exact test). Conclusions: It was suggested that many gastric cancer patients deteriorated rapidly at PD if the same CTx continued after doubled increase of TM without PD.
Abstract MIP-070: THE IMPACT OF HBO1 IN OVARIAN CANCER
Authors: M. Quintela, L. Francis, D.H. Sieglaff, P. Webb, S. Conlan
Journal: Clinical Cancer Research (2017)

Abstract Epithelial ovarian cancer (OC) is now the fifth leading cause of cancer death among women in the U.S. and the leading cause of death in gynecological cancers. OC comprises a variety of tumor types (histotypes) that differ in morphology, prognosis, etiology and molecular biology. Despite the knowledge of OC heterogeneity, current treatment strategies are very similar, and unfortunately, very ineffectual. New approaches, to inhibit OC growth and progression are therefore being sought, with few obvious targets for directed therapy. Currently, large–scale gene expression, DNA copy number and mutational screens have not been able to pinpoint new high frequency drugable targets. Epigenetic therapy conceives a whole genome approach, potentially circumventing the reliance on therapies that target infrequently mutated genes. Histone acetyl–transferases like GCN5 and PCAF have been targeted in cancer previously, and the main purpose of this study is to assess the role of one such acetyl–transferase, Histone acetyl–transferase binding to origin of replication complex 1” (HBO1, also known as KAT7 and MYST2) in the progression of OC. HBO1 is a histone acetyltransferase (HAT) that plays important roles in diverse molecular processes including DNA replication, transcription and DNA repair. Importantly, HBO1 is overexpressed in primary cancers (breast, testis, ovarian), although the molecular basis of its role is still unclear. To better understand HBO1's role in OC, we characterized its expression in well–defined OC cell lines both at the mRNA and protein level. Observed in vitro patterns of HBO1 expression correlate well with previous observations; HBO1 is overexpressed in several OC cell lines. Interestingly, the serous histotype generally shows the highest expression. Thus far, we have now analyzed HBO1's downstream regulatory pathways in several OC cell lines through use of siRNA knock–down coupled to microarray analysis. Comparisons of the various datasets have revealed pathways common to all cell lines studied, as well as distinction. Our approach aims to identify known epigenomic signatures that may be associated with HBO1 binding and downstream signaling which may drive differentiation toward the most advanced stages of the disease. Translating this new information through epigenetic targeting and structural inhibition may lead to novel, next–generation therapies for this most complex of disease presentations. Citation Format: M.Quintela, L.Francis, D.H.Sieglaff, P.Webb, S.Conlan. THE IMPACT OF HBO1 IN OVARIAN CANCER [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr MIP-070.
A case–control study to assess the effectiveness of pertussis vaccination during pregnancy on newborns, Valencian community, Spain, 1 March 2015 to 29 February 2016
Authors: Juan Bellido-Blasco, Silvia Guiral-Rodrigo, Ana Míguez-Santiyán, Antonio Salazar-Cifre, Francisco González-Morán
Journal: Eurosurveillance (2017)

In the Valencian Community (Spain), the programme of maternal pertussis vaccination during pregnancy started in January 2015. The objective of this study was to estimate in this region the vaccine effectiveness (VE) in protecting newborns against laboratory-confirmed pertussis infection. A matched case–control study was undertaken in the period between 1 March 2015 and 29 February 2016. Twenty-two cases and 66 controls (+/− 15 days of age difference) were included in the study. Cases were non-vaccinated infants &lt; 3 months of age at disease onset testing positive for pertussis by real-time PCR. For every case three unvaccinated controls were selected. Odds ratios (OR) were calculated by multiple conditional logistic regression for association between maternal vaccination and infant pertussis. Other children in the household, as well as mother- and environmental covariates were taken into account. The VE was calculated as 1 − OR. Mothers of five cases (23%) and of 41 controls (62%) were vaccinated during pregnancy. The adjusted VE was 90.9% (95% confidence interval (CI): 56.6 to 98.1). The only covariate in the final model was breastfeeding (protective effect). Our study provides evidence in favour of pertussis vaccination programmes for pregnant women in order to prevent whooping cough in infants aged less than 3 months.
Randomized phase III clinical study comparing postoperative UFT/LV,UFT+LV/UFT and UFT+LV+PSK/UFT+PSK as adjuvant therapy for curatively resected stage III colorectal cancer HGCSG-CAD study.
Authors: Toshiaki Shichinohe, Yoshito Komatsu, Kohei Akazawa, Satoshi Yuki, Hiraku Fukushima, Kouichi Ohno, Fumitaka Nakamura, Takaya Kusumi, Takayuki Morita, Naoto Senmaru, Naoko Kumagai, Satoshi Hirano
Journal: Journal of Clinical Oncology (2013)

3638 Background: Study showed that the oral anticancer agent UFT/LV is useful as postoperative adjuvant chemotherapy for stage III colorectal cancer. PSK, a protein-bound polysaccharide extracted from the mycelia of Coriolus versicolor, is an immunomodulator widely used in gastric, colorectal and lung cancers. Methods: Patients aged 20-80 years with stage III colorectal cancer registered in 35 facilities were randomized to: group A (UFT/LV 28 days/5 weeks for 6 months); group B (UFT+LV 28 days/5 weeks for 6 months, then UFT for 12 months); and group C (UFT+LV+PSK 28 days/5 weeks for 6 months, then UFT+PSK for 12 months). Treatment was started within 6 months after curative resection. Outcome measures were relapse-free survival (RFS), overall survival (OS), incidence and severity of adverse events, and QOL. Results: Of 342 patients registered, 340 eligible patients were analyzed (84 in group A, 85 in group B, and 171 in group C). At baseline, variation in QOL score was observed but histopathological parameters were not different among 3 groups. Median observation period was 36 months. 3-year RFS was 73.8%, 77.6% and 73.9% in groups A, B, and C [A vs C: hazard ratio (HR) 0.960, 95% confidence interval (CI) 0.575-1.601; B vs C: HR 0.837, CI 0.488-1.433; A vs B: HR 1.151, CI 0.623-2.126]. 3-year OS was 95.2%, 91.8% and 89.9% in groups A, B, and C (A vs C: HR 0.460, CI 0.155-1.367; B vs C: HR 0.814, CI 0.338-1.963 A vs B: HR 0.570, CI 0.167-1.947). Adverse events ≥grade 3 included gastrointestinal symptoms and general status. There was no treatment-related death. Excluding high fatigue score in QOL scale that showed pretreatment variation, stratification analysis showed interaction between family score and group, and efficacy was suggested especially in group C with high score (3-yesr RFS: 66.7%, 68.2% and 88.1% in groups A, B, and C. A vs C: HR 3.289, CI 0.951-11.375, B vs C: HR 3.070, CI 0.973-9.685, A vs B: HR 1.084, CI 0.344-3.417). Conclusions: A significant difference in primary endpoint was not detected. Variation in QOL at treatment initiation probably greatly affected outcome. Clinical trial information: NCT00209742.
Performance on the Cardiovascular In-Training Examination in Relation to the ABIM Cardiovascular Disease Certification Examination
Authors: Julia H. Indik, Lauren M. Duhigg, Furman S. McDonald, Rebecca S. Lipner, Jonathan D. Rubright, Steven A. Haist, Naomi F. Botkin, Jeffrey T. Kuvin
Journal: Journal of the American College of Cardiology (2017)
Abnormal bone marrow signal on MRI heralding oncologic diagnoses: A single institution review.
Authors: Gunjan L. Shah, Jamie Michelle Bunch Jarboe, Aaron Seth Rosenberg, Andreas Kirschmer Klein, Furha Iram Cossor
Journal: Journal of Clinical Oncology (2013)

1580 Background: The increased use of magnetic resonance imaging (MRI) has resulted in increased numbers of incidental findings. Oncologists often receive consults for workup of "abnormal marrow signal." As there is no standard evaluation for such findings and the yield of additional evaluation is unclear, we performed a retrospective study of patients evaluated with MRI at Tufts Medical Center (TMC). Methods: With IRB approval, TMC radiology reports were searched from 5/9/05-12/31/08 with GE Centricity Radiology Information System 2.2. Included patients had MRI reports containing the phrases “abnormal bone marrow” or “heterogeneous bone marrow”, but no clear etiology stated. Further workup, including referral to a subspecialist, laboratory, radiographic, or pathologic evaluations, final diagnosis, and last follow up were collected. Results: 29,508 MRIs were performed and 77 patients met search criteria. Median age was 58 years with a median follow-up of 41 months at TMC after qualifying MRI. 40/77 (52%) of patients had either an MRI of the lumbar spine or hip with 21/77 (27%) undergoing work-up for the marrow findings. Evaluations included CBC (38%), SPEP (24%), quantitative immunoglobulins (14%), free light chains (10%), peripheral blood flow cytometry (5%), bone marrow biopsy (19%), skeletal survey (14%), bone scan (48%), CT scan (24%), biopsy of other site (24%), and subspecialty referal (48%, 29% to oncology). Definitive diagnosis was assigned in 11/21 (52%) cases, with 5 being malignancies (1 follicular lymphoma, 2 multiple myeloma, 2 lung cancer). Three patients were later diagnosed with malignancy (breast cancer, myelodysplastic syndrome, merkel cell carcinoma) at a median of 19 months. Overall, 10% of patients with abnormal marrow on MRI were diagnosed with a malignancy. Conclusions: Incidentally noted abnormal or heterogeneous bone marrow signal on MRI was not inconsequential. Of those patients who underwent evaluation for the finding, 24% were diagnosed with a malignancy. We conclude that abnormal bone marrow findings on MRI should not be ignored, and given the rates of malignancy in our series, oncologists are ideally suited for this task.