tbuckley/cabot-search huggingface dataset:
Phase 3 study evaluating efficacy and safety of veliparib (V) plus carboplatin (Cb) or Cb in combination with standard neoadjuvant chemotherapy (NAC) in patients (pts) with early stage triple-negative breast cancer (TNBC).
Authors: Charles E. Geyer, Joyce O'Shaughnessy, Michael Untch, William Sikov, Hope S. Rugo, Mark D. McKee, Jens Bodo Huober, Mehra Golshan, Vincent L. Giranda, Gunter Von Minckwitz, David Maag, Danielle Marie Sullivan, Norman Wolmark, Kristi McIntyre, Jose Juan Ponce Lorenzo, Otto Metzger Filho, Priya Rastogi, William Fraser Symmans, Xuan Liu, Sibylle Loibl
Journal: Journal of Clinical Oncology (2017)

520 Background: Clinical studies suggest that TNBC is sensitive to DNA-damaging agents, including Cb. V is a potent PARP inhibitor that may enhance the antitumor activity of such agents. We present primary response data from a phase 3 randomized, placebo-controlled study (NCT02032277) evaluating the addition of V + Cb or Cb to neoadjuvant paclitaxel (P) followed by doxorubicin + cyclophosphamide (AC). Methods: Pts with histologically confirmed, invasive TNBC (T2–T4 N0–2 or T1 N1–2) amenable to surgical resection were randomized 2:1:1 to (Arm A) P 80 mg/m 2 weekly + Cb AUC 6 mg/mL/min q3 weeks + V 50 mg PO BID; (Arm B) P + Cb + PO placebo; or (Arm C) P + IV placebo + PO placebo, for 12 weeks followed by AC (60 mg/m 2 or 600 mg/m 2 q2 or 3 weeks) × 4. Primary endpoint was pathologic complete response (pCR) in breast and nodes with &gt; 80% power at 2-sided α of 0.05 using pair-wise comparisons for A vs B and A vs C to detect significant treatment effects using Χ 2 test; secondary endpoint was rate of conversion to eligibility for breast conservation surgery (BCS). Adverse events (AEs) were assessed with NCI CTCAE V4.0. Results: Six hundred thirty-four pts (median age 50 years; range 22–79) were randomized to Arms A (n = 316), B (n = 160), or C (n = 158). Baseline characteristics were well balanced. No pCR difference was observed between Arms A and B (53.2% vs 57.5% p = 0.36), but pCR in Arm A was higher than Arm C (53.2% vs 31.0% p &lt; 0.001). In non-prespecified analysis, pCR in Arm B was also higher than Arm C (57.5% vs 31.0% p &lt; 0.001). Among pts ineligible for BCS at screening (n = 141), 62% were eligible after NAC in Arm A vs 44% each in Arms B (p = 0.13) and C (p = 0.14). Grade 3–4 AEs (Arms A/B/C, 86%/85%/45%) and serious AEs (30%/27%/14%) neutropenia, thrombocytopenia, anemia, nausea, and vomiting were increased with the addition of Cb; V did not impact toxicity. Median cycles of NAC were not reduced with V + Cb + P or Cb + P vs P. Conclusions: Addition of V to neoadjuvant Cb + P followed by AC did not increase pCR rate in breast and nodes in stage II–III TNBC, while addition of V + Cb or Cb alone to P followed by AC did. Cb (+/– V) increased toxicity but did not impact delivery of NAC. Clinical trial information: NCT02032277.
First genetic medicines available in five years
Authors: Zosia Kmietowicz
Journal: BMJ (2000)

The Nuffield Trust has called on the government to develop a policy framework to regulate developments in genetics.

In its report Genetics and Health the trust acknowledges that advances in genetic science will deliver a “revolution” in medicine and warns that ground work needs to done now to ensure that the potential benefits of genetic discoveries are delivered and that the public is prepared for what is to come and protected by agreements on confidentiality.

“In recent years …
Melatonin, electromagnetic fields, and cancer
Authors: Ravindra Tiwari, Yog Ahuja, K Lakshmi, C Bhargava
Journal: Clinical Cancer Research (2007)

A23   Melatonin production is a highly conserved evolutionary phenomenon. The indole hormone is synthesized in the pinealocytes derived from photoreceptors. Altered patterns and/or levels of melatonin secretion have been reported to coincide with sleep disorders, jetlag, depression, stress, reproductive activitives, some forms of cancer, and immuological disorders. An important hallmark of modern society is the pervasive use of electric power producing light at night (LAN) and electromagnetic fields (EMFs) which may alter the pineal function and synthesis of melatonin. According to the 9melatonin hypothesis9 of cancer, exposure to anthropogenic EMFs is related to increased incidence of breast cancer and childhood leukemia via melatonin disruption. Lately, the physiological and pathological role of melatonin has become a priority area of investigations, particularly in cancers of the breast, colon, lung, prostate, melanoma, and leuekmia. Melatonin9s hypothermic, antioxidant, and free radical scavenging properties attribute to it an oncostatic agent and an immunomodulator as well. Many clinical studies have envisaged the potential therapeutic role of melatonin in various pathophysiological disorders of cancer. Melatonin as an oncostatic agent promotes the stabilization of the disease and induces objective tumor regression in synergy with a chemotherapeutic agent. Current medical literature reveals that melatonin has a multidisciplinary anticancer action, as it reduces the toxicity after radiotheraphy, immuno-hormonal therapy and cancer surgery. A substantial reduction in risk of death and low adverse effects were reported from various randomized controlled trials of melatonin treatment in cancer patients with disease free progression of at least one year survival. The presentation focuses on melatonin hypothesis to represent the cause-effect relationship of the three aspects: LAN, EMFs and cancer. Furthermore, this review deals with physiological significance of melatonin and its potential role in cancer therapy.
Duration of second-line T-DM1 therapy: Is it associated with duration of first-line anti-Her2 therapy in metastatic HER2 + breast cancer?
Authors: Daniela Katz, Ilan Feldhamer, Sari Greenberg-Dotan, Ariel Hammerman
Journal: Journal of Clinical Oncology (2017)

e12512 Background: Tumors with HER2 overexpression usually respond to HER2-targeted therapies. Since the CLEOPATRA and EMILIA trials, a taxane plus trastuzumab and pertuzumab (TTP) are the first-line standard for the management of HER2 + metastatic breast cancer (MBC) and trastuzumab emtansine (TDM-1) is the second-line standard. Intrinsic subtypes existing within HER2+ tumors may impact the degree of a patient’s response to anti HER2 therapy; however HER2 subtyping for predicting response is still experimental and not in routine clinical use. In this retrospective population-based study, we aimed to assess whether duration of treatment (DOT) of second-line TDM1 is associated with the DOT of first-line TTP, and might serve as a hint for a HER2 subtype. Methods: Clalit Health Services (CHS) manages health care of 52% of the Israeli population. We identified 113 HER2+ CHS MBC patients, treated with TTP as first-line treatment that initiated TDM1 as second-line, until Dec. 31, 2016. Patient's (pts) demography, HER2 and HR status were recorded. A Cox proportional hazard model, stratified by HR status, adjusted for age and prior adjuvant trastuzumab, was used to explore the association between second-line and first-line DOT in HR positive and negative pts. Results: Pts baseline characteristics and DOT in first- and second-line treatment are presented in the table. A statistically significant association between DOT of both treatment lines was found in HR positive pts with a trend also in HR negative pts. Conclusions: The observed association between first- and second-line DOT, unrelated to hormonal status, may result from a primary characteristic of the intrinsic tumor subtype, that impacts acquired resistance. Longer observations in larger patient cohorts are required to confirm this observation. [Table: see text]
Does tumor size in T1-T2 early breast cancer (EBC) still have a prognostic role?
Authors: Anaid Anna Kasangian, Anna Moretti, Elena Biagioli, Elena Bernardin, Andrea Cordovana, Giorgio Gherardi, Gabriella Farina, Annalisa Bramati, Sheila Piva, Maria Chiara Dazzani, Emanuela Paterno, Nicla Maria La Verde
Journal: Journal of Clinical Oncology (2017)

e12087 Background: Theprognosis of EBC patients (pts) depends on pts characteristics and tumor biological/ histopathological features. The correlation between tumor size, expressed as the largest diameter in TNM staging, and overall survival (OS) and disease free survival (DFS) is well recognized. According to TNM, tumors classified as T2, could have different volumes (V); e.g. a tumor of 2,1 cm has a V of 4500 mm 3 , while a tumor of 4,9 cm has a V of 60000 mm 3 . Despite belonging to the same class, the two different V may have a different prognosis. The aim of the study is to establish if the role of tumor size has been surpassed by other factors. Methods: The purpose is to evaluate the correlation between V and DFS/OS, in a T1-T2 population, who underwent breast surgery and sentinel lymph node biopsy, in our institution from 01.01.2005 to 30.09.2013. V was evaluated with the measurement of three half-diameters of the tumor (a, b and c), and calculated with this formula: 4/3 * π * a * b * c. Results: 341 pts with T1-T2 EBC who underwent surgery were included. 86,5% were treated with conservative surgery. 85,1% had a luminal subtype, 9,1% triple negative (TN) and 7,4% Her2 positive (+). Median V was 942 mm 3 (range 0,52-31651,2). 44 pts (12,9%) relapsed and 23 pts died. With a median follow-up of 6,5 years, the univariate analysis for DFS showed a correlation between age (p 0,016), tumor size (p 0,032), V (p 0,078), histological grading (p 0,001), molecular subtype (p &lt; 0,001). The multivariate analysis confirmed the statistically significant correlation only for molecular subtype (p 0,005), showing a worse prognosis for TN and Her2+ subtypes. Regarding OS, a statistically significant correlation was shown by the univariate analysis both for histological grading (p 0,018) and molecular subtype (p 0,001). The multivariate analysis confirmed that TN and Her2+ subtypes negatively influence OS (p 0,005). Conclusions: In our study neither V nor tumor diameter seem to correlate with DFS and OS in T1-T2 tumors; the only parameter that strongly influences DFS and OS, is molecular subtype, confirming the worse prognosis of TN and Her2+ versus luminal tumors. These findings encourage clinics to choose adjuvant treatment not based on dimensional criteria but on biological features.
The natural history of progression to PSA recurrence and metastasis among at risk men following radical prostatectomy.
Authors: Ashley Ross, Mercedeh Ghadessi, Debasish Sundi, Misop Han, Elizabeth B. Humphreys, Elai Davicioni, Alan W. Partin, Patrick C. Walsh, Edward M. Schaeffer
Journal: Journal of Clinical Oncology (2014)

5036 Background: Active surveillance for low risk disease has been gaining acceptance with the aim of preferentially treating men with NCCN intermediate and high risk prostate cancer. Currently used outcome estimates however, were developed using cohorts, which included a high proportion of men with low or very low- risk disease. Here we describe the natural history of intermediate and high-risk prostate cancer treated only by radical prostatectomy (RP). Methods: Men who underwent RP in the PSA era, initially had undetectable PSAs after surgery, and received no post-RP therapy prior to metastasis were included (1,739 men). Biochemical recurrence (BCR) was defined by a PSA of ≥0.2 ng/ml and metastasis was diagnosed by axial imaging or bone scan. Results: Median follow up was 10 years and 17% developed BCR with a median time to BCR of 3 years (range 1-18). Of men with BCR, 41% developed metastasis (median time 3 years (range 0-11) after BCR). Median time from metastasis to death was 4 years (range 0-11). Men with metastasis had higher median CAPRA-S and Stephenson scores than those without metastatic progression (6 vs. 2 and 0.28 vs. 0.04, respectively, p<0.001 for both) but the range of scores was broad (1-12 vs. 0-10 and 0.02-0.95 vs. 0.01-0.71 respectively). Following BCR, the cumulative incidence of metastasis among intermediate and high-risk men was similar (p=0.57) as was the cumulative incidence of death after metastasis (p=0.69). The AUC for predicting metastasis after BCR was 0.67 for the Stephenson and 0.55 for CAPRA-S scores. Conclusions: As practice patterns shift towards the treatment of higher risk localized disease, point estimates for the time to BCR, metastatic progression, and death shorten accordingly. In addition, the predictive ability of clinicopathologic variables and nomograms is significantly diminished. This highlights the need for additional information (i.e. molecular markers) to help guide treatment decisions among at risk men following radical prostatectomy.
Genomic Medicine
Authors: Roger L Albin
Journal: New England Journal of Medicine (2003)

the authors reply: Drs.Cuzin and Alvarez report that "in cases of high-risk exposure" the highest rate of HIV transmission is around 0.3 percent.Prospective studies suggest that this rate represents the av-erage risk of transmission after percutaneous exposure to HIV-infected blood, but the risk is probably higher after exposure involving an increased volume of blood or a high viral load, 1,2 both of which might apply to health care workers exposed to patients with resistance to antiretroviral drugs -a possible reason for the failure of postexposure prophylaxis.We recommend the restricted use of prophylactic enfuvirtide in high-risk persons, 3 such as health care workers, in a setting where the storage, preparation, and administration of the drug are performed by skilled personnel.
Targeted intraoperative radiotherapy tumor bed boost during breast conserving surgery after neoadjuvant chemotherapy in hormone receptor positive HER2 negative breast cancer.
Authors: Hans-Christian Kolberg, Gyoergy Loevey, Leyla Akpolat-Basci, Miltiades Stephanou, Peter A. Fasching, Michael Untch, Max Bulsara, Jayant S. Vaidya, Cornelia Liedtke
Journal: Journal of Clinical Oncology (2017)

e12090 Background: Targeted intraoperative radiotherapy (TARGIT – IORT) as a tumor bed boost during breast conserving surgery is an established option for women with early breast cancer. In a previous study our group could show a beneficial effect of TARGIT-IORT on overall survival after neoadjuvant chemotherapy compared to an external boost in an unselected cohort. In this study we present an analysis of the hormone receptor positive HER2 negative subgroup. Methods: In this non-randomized cohort study involving 46 hormone receptor positive HER2 negative patients after NACT we compared outcomes of 21 patients who received a tumour bed boost with IORT (TARGIT-IORT) during lumpectomy versus 25 patients treated in the previous 13 months with external (EBRT) boost. All patients received whole breast radiotherapy. Disease free survival (DFS) and overall survival (OS) were compared. Results: There were no statistical differences between the two groups regarding tumor size, grading, nodal status and pCR rates. Median follow up was 49 months. Whereas DFS was not significantly different between the groups the 5-year Kaplan-Meier estimate of OS was significantly better by 21% with IORT: TARGIT-IORT 0 events 100%, EBRT 5 events 79%, log rank p = 0.028. Conclusions: Although our results have to be interpreted with caution due to a possible selection bias and the small numbers, we could show that the improved OS as previously demonstrated in our dataset for TARGIT-IORT during lumpectomy after neoadjuvant chemotherapy as a tumor bed boost compared to an external beam radiotherapy boost is driven by the hormone receptor positive HER2 negative subgroup. These data give further support to the inclusion of such patients in the TARGIT-B (Boost) randomised trial that is testing whether IORT boost is superior to EBRT boost and to the analysis of subgroups based on tumor biology in this trial.
PCSK9 Is Increased in Youth With Type 1 Diabetes
Authors: Amy E. Levenson, R. Paul Wadwa, Amy S. Shah, Philip R. Khoury, Thomas R. Kimball, Elaine M. Urbina, Sarah D. de Ferranti, Franziska K. Bishop, David M. Maahs, Lawrence M. Dolan, Sudha B. Biddinger
Journal: Diabetes Care (2017)

Type 1 diabetes (T1D) is associated with a 10-fold increase in cardiovascular disease (CVD) risk, due in part to dyslipidemia. Patients with poorly controlled T1D show an increase in total and LDL cholesterol as well as elevated apolipoprotein B (ApoB) levels. Moreover, even patients with well-controlled T1D can show increased levels of ApoB. Dyslipidemia is particularly important in females with T1D, as the atheroprotective lipoprotein profile and reduced risk of CVD usually observed in females without diabetes are lost in females with diabetes (1,2).

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has recently emerged as a novel regulator of plasma cholesterol levels: gain-of-function PCSK9 mutations increase LDL cholesterol and CVD risk, whereas inhibitors of PCSK9 lower LDL cholesterol. Although PCSK9 is increased in individuals with obesity and type 2 diabetes (3,4), it is not known whether PCSK9 levels are also changed in individuals with T1D.

Here, we measured PCSK9 levels in a subset of a previously described cohort of T1D and control subjects (5). For the current study, subjects with serum available for PCSK9 measurement were matched for age and sex between each group using the frequency matching method. Subjects who reported taking statin medications at the time of the study were excluded from the analyses ( n = 3, all from T1D …
Alcohol consumption and brain health
Authors: Killian A Welch
Journal: BMJ (2017)

Epidemiological studies often report better heath in moderate drinkers compared with abstainers. Observed first in studies of incidence of myocardial infarction,1 the “J shaped curve” (describing the graphical appearance of health measures plotted against consumption) reappears in studies of diabetes, stroke, and even chronic widespread pain.2 As methods of investigating the association between alcohol and health are refined, however, the size of the apparent benefits reduces substantially.3 Studies using “Mendelian randomisation,” purportedly impervious to confounding or reverse causality, do not support the original claim that moderate drinking improves cardiovascular health.4......
DRUGS AND BASAL METABOLISM
Journal: JAMA (1924)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Interrupted Glucagon Signaling Reveals Hepatic α Cell Axis and Role for L-Glutamine in α Cell Proliferation
Authors: E. Danielle Dean, Mingyu Li, Nripesh Prasad, Scott N. Wisniewski, Alison Von Deylen, Jason Spaeth, Lisette Maddison, Anthony Botros, Leslie R. Sedgeman, Nadejda Bozadjieva, Olga Ilkayeva, Anastasia Coldren, Greg Poffenberger, Alena Shostak, Michael C. Semich, Kristie I. Aamodt, Neil Phillips, Hai Yan, Ernesto Bernal-Mizrachi, Jackie D. Corbin, Kasey C. Vickers, Shawn E. Levy, Chunhua Dai, Christopher Newgard, Wei Gu, Roland Stein, Wenbiao Chen, Alvin C. Powers
Journal: Cell Metabolism (2017)
Number of cases of syphilis continue to rise
Authors: Anne Gulland
Journal: BMJ (2017)

The number of cases of syphilis has hit the highest level since 1949, according to figures published by Public Health England.1

There were 5920 cases of the infection reported in 2016, a 12% rise from 2015 when 5281 cases were reported. Since 2012—when there were 3001 infections—the number of cases has nearly doubled.

Public Health England (PHE) says that most of the increase is associated with transmission among gay, bisexual, and other men who have sex with men.

The figures show that there has been a slight decrease in the number of sexually transmitted infections (STIs) overall. In 2016 there were around 420 000 diagnoses of STIs, a decline of 4% compared …
Regulatory Science in Neonates
Authors: Mark A. Turner, Ronald J. Portman, Jonathan M. Davis
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Prediction of outcome in newly diagnosed myeloma: a meta-analysis of the molecular profiles of 1905 trial patients
Authors: V Shah, A L Sherborne, B A Walker, D C Johnson, E M Boyle, S Ellis, D B Begum, P Z Proszek, J R Jones, C Pawlyn, S Savola, M W Jenner, M T Drayson, R G Owen, R S Houlston, D A Cairns, W M Gregory, G Cook, F E Davies, G H Jackson, G J Morgan, M F Kaiser
Journal: Leukemia (2017)

Robust establishment of survival in multiple myeloma (MM) and its relationship to recurrent genetic aberrations is required as outcomes are variable despite apparent similar staging. We assayed copy number alterations (CNA) and translocations in 1036 patients from the NCRI Myeloma XI trial and linked these to overall survival (OS) and progression-free survival. Through a meta-anlysis of these data with data from MRC Myeloma IX trial, totalling 1905 newly diagnosed MM patients (NDMM), we confirm the association of t(4;14), t(14;16), t(14;20), del(17p) and gain(1q21) with poor prognosis with hazard ratios (HRs) for OS of 1.60 (P=4.77 × 10−7), 1.74 (P=0.0005), 1.90 (P=0.0089), 2.10 (P=8.86 × 10−14) and 1.68 (P=2.18 × 10−14), respectively. Patients with 'double-hit' defined by co-occurrence of at least two adverse lesions have an especially poor prognosis with HRs for OS of 2.67 (P=8.13 × 10−27) for all patients and 3.19 (P=1.23 × 10−18) for intensively treated patients. Using comprehensive CNA and translocation profiling in Myeloma XI we also demonstrate a strong association between t(4;14) and BIRC2/BIRC3 deletion (P=8.7 × 10−15), including homozygous deletion. Finally, we define distinct sub-groups of hyperdiploid MM, with either gain(1q21) and CCND2 overexpression (P<0.0001) or gain(11q25) and CCND1 overexpression (P<0.0001). Profiling multiple genetic lesions can identify MM patients likely to relapse early allowing stratification of treatment.