tbuckley/cabot-search huggingface dataset:
Early prediction of pathological complete response (pCR) of rectal cancer after 1 week of preoperative radiochemotherapy (RCT) using positron emission computererized tomography (PET-CT) imaging.
Authors: O. Purim, N. Goldberg, Y. Kundel, R. Brenner, N. Efremov, N. Gordon, S. Morgenstern, N. Wasserberg, B. Brenner
Journal: Journal of Clinical Oncology (2011)

572 Background: Preoperative radiochemotherapy (RCT) is the standard treatment of locally advanced rectal cancer (LARC), obtaining pathological complete response (pCR) in 15%-30% of cases. Post-RCT reduction of 18F-fluorodeoxyglucose (FDG) uptake within the tumor compared with the baseline, i.e. the tumor's metabolic response, correlates with pCR. However, an earlier prediction of pCR could enable tailored modifications of the treatment. We hence evaluated the correlation between the metabolic response after only one week of RCT for LARC and the actual pCR at the post-RCT surgery. Methods: Patients (pts) were eligible for this prospective study if they had LARC, defined as T3-4NX or TxN+ tumors by pre-treatment PET-CT and endoscopic ultrasound. Pts received standard RCT regimen, consisting of 50.4Gy radiotherapy concurrently with a fluoropyrimidine-based chemotherapy, followed by surgery. Pts underwent baseline FDG-PET-CT imaging within 2 weeks prior to the initiation of RCT and a second one on day 8 of RCT. Maximum standardized uptake value (SUV-max) was measured in both scans and changes in FDG- uptake were recorded. Man-Whitney test was used to evaluate differences in the SUV-max between baseline and day 8 in pts obtaining pCR and those who did not. Results: Twenty pts participated in the study. Half were males and the median age was 64 years. Ten pts had T3N0 tumors and 10 had T3N+ disease. Radical surgery was done in 19 pts and local excision in one. Considering the entire group, there was a borderline-significant difference between the metabolic response of pts with pCR and those without pCR (Chi-square = 3.429, p = 0.064). Yet, the changes in FGD-uptake were able to identify pts who achieved pCR and those who did not: only pts with a decrease of more than 33% in SUV-max had pCR while none of the pts who had less than 8.9% decrease in SUV-max had pCR. Conclusions: A decrease in SUV-max between baseline-PET-CT scans and scans done after only one week of RCT for LARC may be able to predict the achievement of pCR in the post-RCT surgical specimen. Validation in a larger independent cohort is planned. No significant financial relationships to disclose.
Phase II trial of docetaxel, cisplatin, 5-fluorouracil (TPF) in locally advanced and metastatic squamous cell carcinoma (SCC) of the penis (CRUK/09/001).
Authors: Amit Bahl, Steve Nicholson, Stephen John Harland, John D. Chester, Lisa M. Pickering, Jim Barber, Clare Cruickshank, Stephanie M. Burnett, Rachel Waters, Emma Hall
Journal: Journal of Clinical Oncology (2012)

326 Background: Chemotherapy for penis cancer is used to palliate metastatic disease and treat locally-advanced disease. Pathologic similarities to head and neck SCC suggest that adding docetaxel (T) to platinum-based regimens may enhance efficacy. Methods: A single-stage single-arm phase II trial was conducted. Eligible patients had measurable, histologically proven penile SCC staged M1; or T4, any N, M0; or any T, N3/inoperable N2, M0; or any T, N1, M0 with Multi-Disciplinary Team agreement for chemotherapy as first-line therapy. Treatment was three 21-day cycles of TPF (day 1: T 75mg/m 2 , P 60mg/m 2 ; days 1-5: F 750mg/m 2 /day). In 26 evaluable patients ≥14 responses were required to conclude a response rate of ≥60% (p0=0.35, p1=0.60, α=0.1, β=0.2; Fleming-A’Hern design). Primary endpoint was overall response rate at completion/discontinuation of trial treatment. Secondary endpoints included safety, tolerability, progression-free survival (PFS) and overall survival (OS). Results: 29 patients (median age 61 years) were recruited from 9 UK centres between Sept 2009 and Dec 2010. 8 patients were M1. 17 patients had performance status (PS) 0, 11 PS1, 1 PS2. 3 patients discontinued treatment early for reasons other than progression. Dose reductions/delays were reported for 13 patients. 28 patients have on-treatment toxicity data: 19 (68%) experienced grade 3/4 toxicity, with neutropenia most common (n=13, 46%). 7 patients (25%) experienced febrile neutropenia and/or neutropenic sepsis. 10/26 patients (38.5%, 95% CI: 20.2% - 59.4%) in the evaluable population responded. Twelve month PFS was 39.1% (95% CI: 20.9% - 56.8%; median PFS (all 29 patients/M1/M0): 7.1/ 3.1/ 9.6- months). Twelve month OS was 54.6% (34.9% - 70.6%; median OS (all patients/M1/M0): 13.7/ 6.9/ not reached yet-months). Conclusions: UK clinicians successfully recruited to a multi-centre trial in penis cancer, establishing a network of centres for future studies. Toxic effects of TPF were common but not unexpected. The trial did not reach its target response rate of ≥60% to justify further investigation although PFS and OS in this cohort compares favourably to reported data in literature.
Evolution of the immune system influences speciation rates in teleost fishes
Authors: Martin Malmstrøm, Michael Matschiner, Ole K Tørresen, Bastiaan Star, Lars G Snipen, Thomas F Hansen, Helle T Baalsrud, Alexander J Nederbragt, Reinhold Hanel, Walter Salzburger, Nils C Stenseth, Kjetill S Jakobsen, Sissel Jentoft
Journal: Nature Genetics (2016)

Kjetill S. Jakobsen, Sissel Jentoft and colleagues assemble partial draft genomes and analyze sequences from 66 teleost fish species to determine major histocompatibility complex (MHC) class I and class II gene status. They find that MHC II is absent from the Gadiformes lineage, while MHC I gene expansions have occurred multiple times. Teleost fishes constitute the most species-rich vertebrate clade and exhibit extensive genetic and phenotypic variation, including diverse immune defense strategies. The genomic basis of a particularly aberrant strategy is exemplified by Atlantic cod, in which a loss of major histocompatibility complex (MHC) II functionality coincides with a marked expansion of MHC I genes. Through low-coverage genome sequencing (9–39×), assembly and comparative analyses for 66 teleost species, we show here that MHC II is missing in the entire Gadiformes lineage and thus was lost once in their common ancestor. In contrast, we find that MHC I gene expansions have occurred multiple times, both inside and outside this clade. Moreover, we identify an association between high MHC I copy number and elevated speciation rates using trait-dependent diversification models. Our results extend current understanding of the plasticity of the adaptive immune system and suggest an important role for immune-related genes in animal diversification.
Coffee, Caffeine, and Health Outcomes: An Umbrella Review
Authors: Giuseppe Grosso, Justyna Godos, Fabio Galvano, Edward L. Giovannucci
Journal: Annual Review of Nutrition (2017)

To evaluate the associations between coffee and caffeine consumption and various health outcomes, we performed an umbrella review of the evidence from meta-analyses of observational studies and randomized controlled trials (RCTs). Of the 59 unique outcomes examined in the selected 112 meta-analyses of observational studies, coffee was associated with a probable decreased risk of breast, colorectal, colon, endometrial, and prostate cancers; cardiovascular disease and mortality; Parkinson's disease; and type-2 diabetes. Of the 14 unique outcomes examined in the 20 selected meta-analyses of observational studies, caffeine was associated with a probable decreased risk of Parkinson's disease and type-2 diabetes and an increased risk of pregnancy loss. Of the 12 unique acute outcomes examined in the selected 9 meta-analyses of RCTs, coffee was associated with a rise in serum lipids, but this result was affected by significant heterogeneity, and caffeine was associated with a rise in blood pressure. Given the spectrum of conditions studied and the robustness of many of the results, these findings indicate that coffee can be part of a healthful diet.
Time from Diagnosis to Treatment Initiation Predicts Survival in Acute Myeloid Leukemia (AML).
Authors: Mikkael A. Sekeres, Paul Elson, Xuemei Wang, Matt Kalaycio, Anjali Advani, Edward Copelan, Stefan Faderl, Hagop Kantarjian, Elihu Estey
Journal: Blood (2007)
Effectiveness of bronchial thermoplasty in patients with severe refractory asthma: Clinical and histopathologic correlations
Authors: Marina Pretolani, Anders Bergqvist, Gabriel Thabut, Marie-Christine Dombret, Dominique Knapp, Fatima Hamidi, Loubna Alavoine, Camille Taillé, Pascal Chanez, Jonas S. Erjefält, Michel Aubier
Journal: Journal of Allergy and Clinical Immunology (2016)
Short-term Effects of Laparoscopic Adjustable Gastric Banding Versus Roux-en-Y Gastric Bypass
Authors: Amalia Gastaldelli, Amerigo Iaconelli, Melania Gaggini, Maria Chiara Magnone, Augusto Veneziani, Francesco Rubino, Geltrude Mingrone
Journal: Diabetes Care (2016)

OBJECTIVE Bariatric surgery has been shown to have important long-term metabolic effects resulting in enhanced insulin sensitivity and improved glucose tolerance in patients with type 2 diabetes. The contribution of reduced caloric intake to these beneficial effects of surgery remains unclear. The aim of this study was to compare the short-term effects (1 week) of bariatric surgical procedures with a very low caloric intake (VLCI) on insulin sensitivity (IS) and insulin secretion (ISR) in nondiabetic obese subjects. RESEARCH DESIGN AND METHODS Twenty obese patients without diabetes (BMI 44.2 ± 0.7 kg/m2) were admitted to the clinic for 1 week. At baseline and 1 week after VLCI (600 kcal/day), subjects received a hyperinsulinemic-euglycemic clamp with tracer infusion to quantify endogenous glucose production (EGP), lipolysis (rate of appearance of glycerol [RaGlycerol]), peripheral insulin sensitivity (insulin-stimulated glucose disposal [M value] divided by the steady-state plasma insulin concentration [M/I]), hepatic insulin sensitivity (Hep-IS [= 1/(EGP ⋅ insulin)]), and adipose insulin sensitivity (Adipo-IS [= 1/(RaGlycerol ⋅ insulin)]). An intravenous glucose bolus was administered at the end of the insulin clamp to measure ISR and β-cell function (disposition index [DI]). Approximately 3 months later, patients were admitted for laparoscopic adjustable gastric banding (LAGB) (n = 10) or Roux-en-Y gastric bypass (RYGB) (n = 10), and were restudied 1 week after surgery under the same caloric regimen (600 kcal/day). RESULTS After 1 week of VLCI, patients lost 2.1 kg without significant changes in Hep-IS, Adipo-IS, M/I, or DI. RYGB and LAGB led to greater weight loss (5.5 and 5.2 kg, respectively) and to significant improvement in Hep-IS, EGP, and lipolysis. Only RYGB improved Adipo-IS and M/I. No change in ISR or DI was observed in either surgical group. CONCLUSIONS Bariatric surgery improves IS within 1 week. These metabolic effects were independent of caloric intake and more pronounced after RYGB compared with LAGB.
Epidemiology of Varicella During the 2-Dose Varicella Vaccination Program — United States, 2005–2014
Authors: Adriana S. Lopez, John Zhang, Mona Marin
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Before availability of varicella vaccine in the United States, an estimated 4 million varicella cases, 11,000-13,500 varicella-related hospitalizations, and 100-150 varicella-related deaths occurred annually. The varicella vaccination program was implemented in the United States in 1996 as a 1-dose routine childhood program. Based on data from two varicella active surveillance sites, the varicella vaccination program led to 90% decline in incidence over the next decade (1). However, because of continued varicella outbreaks, a routine 2-dose schedule (at ages 12-15 months and 4-6 years) was recommended and has been in place since 2006 (2). The declines in incidence (1,3-6) made it feasible for states to implement varicella case-based surveillance and to report varicella data to CDC through the National Notifiable Diseases Surveillance System (NNDSS). State data have become the primary source for monitoring trends in varicella incidence nationally (7). Using NNDSS data, CDC previously reported nationwide declines in varicella incidence of 72% from the end of the 1-dose to the early years of the 2-dose varicella vaccination program (2006-2010) (7). This report updates varicella incidence trends to include the most recent years in the 2-dose varicella vaccination program. Between the period 2005-2006 (before the 2-dose recommendation) and 2013-2014, overall varicella incidence declined 84.6%, with the largest declines reported in children aged 5-9 years (89.3%) and 10-14 years (84.8%). The availability of varicella-specific data varied over time. During the last 2 years examined (2013 and 2014), completeness of reporting of two critical variables monitored by CDC, vaccination status (receipt of at least 1 dose of varicella vaccine) of cases and severity of disease based on number of lesions, were 54.2% and 39.1%, respectively. State and local health departments, in collaboration with CDC, should continue working to improve reporting of cases and completeness of critical varicella-specific variables to better monitor impact of the varicella vaccination program.
Edoxaban Versus Warfarin in Atrial Fibrillation Patients at Risk of Falling
Authors: Jan Steffel, Robert P. Giugliano, Eugene Braunwald, Sabina A. Murphy, Michele Mercuri, Youngsook Choi, Phil Aylward, Harvey White, Jose Luis Zamorano, Elliott M. Antman, Christian T. Ruff
Journal: Journal of the American College of Cardiology (2016)

Anticoagulation is often avoided in patients with atrial fibrillation who are at an increased risk of falling. This study assessed the relative efficacy and safety of edoxaban versus warfarin in the ENGAGE AF–TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis In Myocardial Infarction 48) trial in patients with atrial fibrillation judged to be at increased risk of falling. We performed a pre-specified analysis of the ENGAGE AF–TIMI 48, comparing patients with versus without increased risk of falling. Nine hundred patients (4.3%) were judged to be at increased risk of falling. These patients were older (median, 77 vs. 72 years; p < 0.001), and had a higher prevalence of comorbidities including prior stroke/transient ischemic attack, diabetes, and coronary artery disease. After multivariable adjustment, patients at increased risk of falling experienced more bone fractures caused by falling (adjusted hazard ratio [HRadj]: 1.88; 95% confidence interval [CI]: 1.49 to 2.38; p < 0.001), major bleeding (HRadj: 1.30; 95% CI: 1.04 to 1.64; p = 0.023), life-threatening bleeding (HRadj: 1.67; 95% CI: 1.11 to 2.50; p = 0.013), and all-cause death (HRadj: 1.45; 95% CI: 1.23 to 1.70; p < 0.001), but not ischemic events including stroke/systemic embolic event (HRadj: 1.16; 95% CI: 0.89 to 1.51; p = 0.27). No treatment interaction was observed between either dosing regimens of edoxaban and warfarin for the efficacy and safety outcomes. Treatment with edoxaban resulted in a greater absolute risk reduction in severe bleeding events and all-cause mortality compared with warfarin. Edoxaban is an attractive alternative to warfarin in patients at increased risk of falling, because it is associated with an even greater absolute reduction in severe bleeding events and mortality. (Effective aNticaoGulation with factor xA next Generation in Atrial Fibrillation [ENGAGE AF-TIMI 48]; NCT00781391)
Final analysis of the phase II randomized discontinuation trial (RDT) of tivozanib (AV-951) versus placebo in patients with renal cell carcinoma (RCC).
Authors: D. Nosov, P. Bhargava, W. B. Esteves, A. L. Strahs, O. N. Lipatov, O. O. Lyulko, A. O. Anischenko, R. T. Chacko, D. Doval, W. J. Slichenmyer
Journal: Journal of Clinical Oncology (2011)

4550 Background: Tivozanib is a potent and selective small molecule tyrosine kinase inhibitor (TKI) of VEGFR-1, -2, and -3. Methods: Patients (pts) with advanced RCC (all histologies) and no prior VEGF-targeted therapy were enrolled. All pts received 16 wks of open-label tivozanib 1.5 mg/d, following which pts were stratified: pts with ≥25% tumor shrinkage continued tivozanib, pts with ≥25% tumor increase were discontinued, and pts with <25% tumor change from baseline (SD) were randomized to 12 wks of double-blind (DB) tivozanib or placebo; randomized pts were un-blinded at the time of progressive disease (PD) or at the end of the DB phase, and those on placebo were allowed to restart tivozanib. CT scans were read by blinded, independent reviewers. Results: 272 pts were enrolled: 83% had clear cell RCC, 73% had undergone nephrectomy, and 46% had received prior therapy. In the overall study population, 84% of pts demonstrated PR or SD by Week 16. In the overall population, the ORR was 30%, DCR was 85% and median PFS 11.7 mo. Pts with clear cell histology who had undergone a nephrectomy demonstrated the highest efficacy, with an ORR of 36%, DCR of 88% and median PFS of 14.8 mo. Hypertension (45%) and dysphonia (22%) were the most common drug-related AEs of any grade. There was a low incidence of drug-related diarrhea (12%), asthenia (10%), fatigue (8%), dyspnea (6%), cough (5%), anorexia (5%), stomatitis (4%), hand-foot syndrome (4%) and proteinuria (3%). Grade 3/4 AEs were infrequent; the most common grade 3/4 AE was hypertension, reported in 12% of pts. Conclusions: Tivozanib shows promising efficacy and acceptable safety and tolerability as a selective VEGFR TKI for pts with advanced or metastatic RCC. In the overall study population, the median PFS, DCR and ORR were 11.7 mo, 85% and 30%, respectively. In pts with clear cell RCC who had undergone nephrectomy, tivozanib demonstrated the greatest efficacy, with PFS of 14.8 mo and ORR of 36%. The safety profile was acceptable with a low incidence of off-target toxicities, such as hand-foot syndrome and proteinuria. Based on these results, tivozanib is being evaluated in nephrectomized pts with advance clear cell RCC in the global phase III TIVO-1.
A retrospective analysis of High-Dose Interleukin-2 (HD IL-2) following Ipilimumab in metastatic melanoma
Authors: Elizabeth I. Buchbinder, Anasuya Gunturi, Jessica Perritt, Janice Dutcher, Sandra Aung, Howard L. Kaufman, Marc S. Ernstoff, Girald P. Miletello, Brendan D. Curti, Gregory A. Daniels, Sapna P. Patel, John M. Kirkwood, Sigrun Hallmeyer, Joseph I. Clark, Rene Gonzalez, John M. Richart, Joe Lutzky, Michael A. Morse, Ryan J. Sullivan, David F. McDermott
Journal: Journal for ImmunoTherapy of Cancer (2016)

<h3>Background</h3> High dose interleukin-2 (HD IL-2) can induce durable responses in a subset of patients leading to long-term survival. Immune checkpoint blockade (ICB) has demonstrated similarly durable responses in a larger proportion of patients. However, not all patients respond to immune checkpoint blockade and subsequent therapeutic options need to be explored. <h3>Methods</h3> The PROCLAIM database was queried for patients with metastatic melanoma who had received HD IL-2 after treatment with ipilimumab or without prior ICB. Patient characteristics, toxicity and efficacy were analyzed. <h3>Results</h3> A total of 52 metastatic melanoma patients were treated with high dose IL-2 after ipilimumab and 276 patients were treated with high dose IL-2 without prior ICB. The overall response rate in the prior ipilimumab group was 21&nbsp;% as compared to 12&nbsp;% in the group that had not received prior ipilimumab. The median overall survival, measured from the initiation of HD IL-2 therapy, was 19.3&nbsp;months in the prior ipilimumab group and 19.4&nbsp;months in the no prior ICB group. Toxicities observed on HD IL-2 were relatively equivalent between the groups although there were cases of CTLA4 antibody-induced colitis reported after HD IL-2 treatment and a CTLA4 antibody-induced colitis related death. <h3>Conclusion</h3> In this retrospective analysis HD IL-2 therapy displayed antitumor activity in melanoma patients who progressed following treatment with ipilimumab. Most HD IL-2 toxicity was not worsened by prior ipilimumab therapy except for one treatment related death from colitis. Care should be taken to avoid reactivation of CTLA4 antibody-induced colitis.
Extended-hours hemodialysis is associated with lower mortality risk in patients with end-stage renal disease
Authors: Matthew B. Rivara, Scott V. Adams, Sooraj Kuttykrishnan, Kamyar Kalantar-Zadeh, Onyebuchi A. Arah, Alfred K. Cheung, Ronit Katz, Miklos Z. Molnar, Vanessa Ravel, Melissa Soohoo, Elani Streja, Jonathan Himmelfarb, Rajnish Mehrotra
Journal: Kidney International (2016)
Protection Against Endometrial Carcinoma by Combination-Product Oral Contraceptives
Authors: John R. Evrard
Journal: JAMA (1982)

To the Editor.—  I was quite surprised by the conclusions that were drawn by Hulka and co-workers from a small sample of patients (79 patients with endometrial carcinoma and 203 control subjects) in an article published recently inThe Journal(1982; 247:475). The very factors that predisposed to endometrial carcinoma— hypertension, diabetes, and obesity— are also factors that are relative contraindications to the use of oral hormonal contraceptive agents. Perhaps the reason that fewer women in the endometrial cancer cohort had taken oral contraceptive agents was that their clinicians chose some other method of contraception as more suitable in the hypertensive, diabetic, and obese individual. This would seem to provide a more logical explanation of why fewer individual patients with endometrial cancer had been using oral contraceptive agents, rather than to indicate that the oral contraceptive agents had a protective effect against cancer. The authors' published data are incomplete, in
Incidence of Inflicted Traumatic Brain Injury in Infants—Reply
Authors: John F. P. Bridges
Journal: JAMA (2003)

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