tbuckley/cabot-search huggingface dataset:
Platinum-based neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC): A systematic review and meta-analysis of randomized controlled trials (RCTs).
Authors: Francesca Poggio, Marco Bruzzone, Marcello Ceppi, Noam Falbel Ponde, Giovanni La Valle, Christos Sotiriou, Lucia Del Mastro, Evandro De Azambuja, Matteo Lambertini
Journal: Journal of Clinical Oncology (2018)

595 Background: The role of platinum-based NACT in TNBC is highly controversial and its use is not endorsed by current guidelines in unselected TNBC patients. Our meta-analysis aimed to better evaluate the activity, efficacy and safety of platinum-based NACT in TNBC. Methods: A systematic search of MEDLINE, Web of Knowledge and conference proceedings up to October 31th 2017 was performed to identify RCTs evaluating platinum-based vs. platinum-free NACT in TNBC patients. Summary risk estimates (odds ratio [OR] and hazard ratio [HR] with 95% confidence intervals [CI]) were calculated for the effect of platinum-based vs. platinum-free NACT in terms of pathological complete response (pCR: ypT0/is pN0), event-free survival (EFS), overall survival (OS), and grade 3-4 adverse events (AEs: neutropenia, anemia, thrombocytopenia and neuropathy). Pooled analyses were performed using the fixed- and random-effect models. This study is registered in the PROSPERO website (CRD42018080042). Results: Nine RCTs (n = 2,107 patients) were included. Overall, platinum-based NACT significantly increased pCR rates from 35.7% to 52.1% (OR 1.99, 95% CI 1.51-2.62). The result did not change and remained significant when considering only the 7 RCTs using anthracycline-and taxane-based NACT in both arms (54.1% vs. 38.7%; OR 1.88, 95% CI 1.34-2.63) or the 3 RCTs using the same standard regimen of weekly paclitaxel (± platinum) followed by anthracycline and cyclophosphamide in both arms (54.9% vs. 33.3%; OR 2.53, 95% CI 1.37-4.66). Two RCTs (n = 748) reported on survival outcomes. A non-significant trend for improved EFS favoring platinum-based NACT (HR 0.72, 95% CI 0.49-1.06) was observed, with no difference in OS (HR 0.86, 95% CI 0.46-1.63). Platinum-based NACT was associated with a significantly higher risk of grade 3-4 hematological AEs and no increased risk of grade 3-4 neuropathy. Conclusions: Platinum-based NACT significantly improved pCR with a trend towards improved EFS at the cost of higher risk of hematological toxicities in TNBC. Our findings question the current recommendation to limit the use of platinum-based NACT only to BRCA-mutated breast cancer patients.
Development of Macrolide Resistance and Reinfection in Refractory <i>Mycobacterium avium</i> Complex Lung Disease
Authors: Byung Woo Jhun, Su-Young Kim, Seong Mi Moon, Kyeongman Jeon, O Jung Kwon, Hee Jae Huh, Chang-Seok Ki, Nam Yong Lee, Sung Jae Shin, Charles L. Daley, Won-Jung Koh
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Patients with refractory Mycobacterium avium complex lung disease (MAC-LD) undergo long-term macrolide therapy, but macrolide resistance develops infrequently.Objectives: The aim of this study was to determine whether reinfection was a factor in the low incidence of macrolide resistance in patients with refractory MAC-LD.Methods: Among 481 patients with treatment-naive MAC-LD who started antibiotic treatment between January 2002 and December 2013, we identified 72 patients with refractory disease, characterized by persistently positive sputum cultures despite ≥12 months of treatment. Molecular analyses of the 23S ribosomal RNA gene responsible for macrolide resistance and serial mycobacterial genotyping were performed using stored MAC isolates.Measurements and Main Results: The median duration of treatment was 32 months (interquartile range, 24–41 mo) in 72 patients. After treatment for a median of 33 months (interquartile range, 21–44 mo), macrolide resistance developed in 16 (22%) patients. Molecular analysis of isolates from 15 patients revealed that 80% (12 of 15) had a point mutation at position 2,058 or 2,059 of the 23S ribosomal RNA gene. Of the 49 patients who had stored pre- and post-treatment isolates, mycobacterial genotyping revealed that reinfection by new MAC strains occurred in 36 (73%) patients. New MAC strains were found in 24 (49%) patients, and mixed infections with original and new strains occurred in 12 (24%) patients. Only 13 (27%) patients had persistent infections with their original MAC strains.Conclusions: Refractory MAC-LD is commonly caused by reinfection with new strains rather than persistence of the original strain, which may explain the infrequent development of macrolide resistance in refractory MAC-LD.Clinical trial registered with www.clinicaltrials.gov (NCT00970801).
Neutropenia and response to single agent palbociclib.
Authors: Nicholas Patrick McAndrew, Mark Andrew Dickson, Amy Sanders Clark, Andrea Troxel, Christopher Colameco, Maryann Gallagher, Kristi Gramlich, Kelly Zafman, David J. Vaughn, Gary K. Schwartz, Peter J. O'Dwyer, Angela DeMichele
Journal: Journal of Clinical Oncology (2018)

1043 Background: CDK 4/6 inhibitors have been practice-changing in the treatment of metastatic breast cancer. Their activity against retinoblastoma protein positive (Rb+) breast cancer cells is mediated through cell-cycle arrest at the G1/S checkpoint. The most frequent dose-limiting toxicity is neutropenia (NTP), which, in preclinical studies, also occurs via reversible cell-cycle inhibition. The goal of this study is to determine whether NTP is associated with disease response to single agent palbociclib (PAL) as a predictive biomarker of efficacy. Methods: Blood count and response data were analyzed from two phase II clinical trials at different institutions using single agent PAL in 1) advanced Rb+ solid tumors (the “Penn trial”, n = 137) and 2) advanced liposarcoma (the “MSK trial”, n = 59). The majority of subjects in the Penn trial had breast cancer (45%). The primary endpoint was progression free survival (PFS). For each patient, NTP was examined as cycle 1 nadir absolute neutrophil count (C1ANC) and occurrence of any NTP ≥ Grade 1 (per CTCAE version 3) at any point on trial. Results: Results are shown in the table below. Subjects with C1ANCs in the lower quartile had significant improvement in PFS (compared to those in the upper quartile), as did those with any grade NTP (compared to those without NTP). Results were similar in breast cancer subjects, as well as in multivariate cox regression models. Increasing depth of NTP was also associated with increasing PFS days, and subjects requiring dose modification for NTP also had improved PFS. Conclusions: NTP on single agent PAL is significantly and independently associated with improved PFS. This should prompt both physicians and patients to avoid stopping the drug prematurely because of neutropenic concerns. Future studies should address dosing based on target ANC. Clinical trial information: NCT01037790; NCT01209598.Parameter Subgroup Median PFS (Days) HR (95% CI) C1ANC > 1.9 K/μL 47 - < 0.9 K/μL 144 0.56 (0.37-0.84) Max Grade NTP None 42 - 1 56 0.65 (0.38-1.09) 2 109 0.33 (0.21-0.50) 3 145 0.29 (0.20-0.44) 4 291 0.15 (0.06-0.39) Any Grade 120 0.32 (0.23-0.47) NTP, Breast Only None 28 - Any 121 0.34 (0.12-0.95) Dose Modification No 60 - Yes 128 0.08 (0.03-0.18) C1ANC ≤ 0.9 K/μL (Multivariate Cox) - - 0.54 (0.36-0.81) Any Grade NTP (Multivariate Cox) - - 0.33 (0.23-0.48)
Impact of age on the efficacy of oxaliplatin in the preoperative chemoradiotherapy and adjuvant chemotherapy of rectal cancer: a post hoc analysis of the CAO/ARO/AIO-04 phase III trial
Authors: R.-D. Hofheinz, D. Arnold, E. Fokas, M. Kaufmann, T. Hothorn, G. Folprecht, R. Fietkau, W. Hohenberger, M. Ghadimi, T. Liersch, G.G. Grabenbauer, R. Sauer, C. Rödel, U. Graeven
Journal: Annals of Oncology (2018)

BackgroundThe German rectal cancer trial CAO/ARO/AIO-04 has shown a significant benefit in 3-year disease-free survival (DFS) of adding oxaliplatin to a standard preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy (CRT) and adjuvant chemotherapy in patients with locally advanced rectal cancer. The use of oxaliplatin as adjuvant treatment in elderly patients with colon cancer is controversial. We therefore investigated the impact of age on clinical outcome in the CAO/ARO/AIO-04 phase III trial.Patients and methodsWe carried out a post hoc analysis of the CAO/ARO/AIO-04 phase III trial evaluating primary and secondary end points according to age. Patient and tumor characteristics, NCI CTC adverse events grades 3–4 (version 3.0), dose intensities as well as survival and recurrence data were analyzed in three specified age groups (<60, 60–70, and ≥70 years). The influence of age as a continuous variable on DFS was modeled using a subpopulation treatment effect pattern plot (STEPP) analysis.ResultsA total of 1232 patients were assessable. With the exception of Eastern Cooperative Oncology Group status (P< 0.001), no differences in patient and tumor characteristics were noticed between age groups. Likewise, toxicity pattern, dose intensities of CRT and surgical results were similar in all age groups. After a median follow-up of 50 months, in patients aged <60 years a significant benefit of adding oxaliplatin to 5-FU-based CRT and adjuvant chemotherapy was observed for local (P= 0.013) and systemic recurrences (P= 0.023), DFS (P= 0.011), and even overall survival (OS; P= 0.044). The STEPP analysis revealed improved hazard ratios for DFS in patients aged 40–70 years compared with elderly patients treated with oxaliplatin.ConclusionThe addition of oxaliplatin significantly improved DFS and OS in younger patients aged <60 years with advanced rectal cancer. Patients aged ≥70 years had no benefit.Clinical Trials NumberNCT00349076
Infectious diseases during the European Union training mission Mali (EUTM MLI) – a four-year experience
Authors: Hagen Frickmann, Ralf Matthias Hagen, Florian Geiselbrechtinger, Nagpal Hoysal
Journal: Military Medical Research (2018)

The European Union Training Mission Mali (EUTM MLI) is a multinational military training deployment to the Western African tropical nation of Mali. Based on routinely collected disease and non-battle injury surveillance data, this study quantifies the true impact of infectious diseases for this tropical mission and potential seasonal variations in infectious disease threats. Categorized health events during the EUTM MLI mission and associated lost working days were reported using the EpiNATO-2 report. Infection-related health events were descriptively analyzed for a 4-year period from the 12th week in 2013 to the 13th week in 2017. Aggregated EpiNATO-2 data collected from all missions other than EUTM MLI were used as a comparator. Among the infectious diseases reported by EUTM MLI, non-severe upper respiratory infections and gastrointestinal diseases dominated quantitatively, accounting for 1.65 and 1.42 consultations per 100 person-weeks, respectively. The number of recorded infectious disease-associated lost working days during the whole study interval was 723. Seasonal changes in disease frequency were detectable. More gastrointestinal infections were seen in the rainy season, and more respiratory infections occurred in the dry season; these were associated with peaks of more than 2.5 consultations per 100 person-weeks for both categories. Despite initial concerns focused on tropical infectious diseases during this mission in tropical Mali, upper respiratory tract and gastrointestinal infections predominate. The relatively low number of reported lost working days may indicate that these infections are at the milder end of the spectrum of infectious diseases despite a likely reporting bias.
Optimizing the Balance Between Supervision and Autonomy in Training
Authors: J. Paul Happel, Joan B. Ritter, Brian E. Neubauer
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
EEG for evaluation of “chemobrain.”
Authors: Halle C. F. Moore, Michael W. Parsons, Guang H. Yue, Lisa A. Rybicki, Vlodek Siemionow
Journal: Journal of Clinical Oncology (2012)

1076 Background: Cognitive impairment is a poorly understood and worrisome potential complication of adjuvant chemotherapy (CT). We sought to evaluate electroencephalography (EEG) as a means to measure neurophysiologic function in women receiving CT for early breast cancer. Methods: Women planning to undergo CT for operable breast cancer and age-similar controls were evaluated at baseline, during CT and at 1 year with neurophysiologic assessments. Testing included a brief fatigue inventory (BFI), brief mental fatigue assessment (BMF), Processing Speed Index (PSI) derived from Digit Symbol Coding and Symbol Search subtests of the Wechsler Adult Intelligence Scale, and a sustained elbow flexion physical task (PT). EEG recordings were obtained at rest and after the cognitive and physical tasks. Data were analyzed using repeated measures of analysis of variance. Results: Eight patient/control pairs completed baseline and on-treatment evaluations; 7 pairs also completed the 1 year assessment (1 pair withdrawn due to a second malignancy). Subjective mental fatigue measured by BMF is similar for patients and controls at baseline but BMF scores increase significantly during CT for patients relative to controls (p=0.033), recovering to no difference at one year. Differences in PSI are not observed between patients and controls or at the different time points. BFI scores are greater in patients at all 3 time points but endurance on the PT is no different from controls. During chemotherapy EEG total spectrum amplitudes in patients are greater than in controls at rest (p=0.05) and following both the cognitive (p&lt;0.001) and physical (p&lt;0.001) tasks. EEG activity prior to chemotherapy and at one year is not different between patients and controls. For patients but not controls EEG readings after the cognitive task demonstrate greater amplitude than pre-task readings during the time of CT treatment only (p=0.012) with a similar trend seen for the physical task (p=0.06). Conclusions: Patient-perceived mental and physical fatigue during chemotherapy correspond to significant changes in EEG brain activity patterns but not to cognitive testing or physical endurance testing. EEG may offer a sensitive means to measure alterations in brain function associated with CT.
Association of Maternal Eligibility for the Deferred Action for Childhood Arrivals Program With Citizen Children’s Participation in the Women, Infants, and Children Program
Authors: Maya Venkataramani, Craig Evan Pollack, Lisa Ross DeCamp, Kathryn M. Leifheit, Zackary D. Berger, Atheendar S. Venkataramani
Journal: JAMA Pediatrics (2018)

This study examines the association of maternal eligibility for Deferred Action for Childhood Arrivals (DACA) immigration program with participation of citizen children in the Women, Infants, and Children (WIC) health care and supplemental nutrition program.
Nuclear factor (erythroid-derived 2)-like-2 pathway modulates substance P–induced human mast cell activation and degranulation in the hair follicle
Authors: Laura Jadkauskaite, Rajia Bahri, Nilofer Farjo, Bessam Farjo, Gail Jenkins, Ranjit Bhogal, Iain Haslam, Silvia Bulfone-Paus, Ralf Paus
Journal: Journal of Allergy and Clinical Immunology (2018)
Multifactorial Brugada Phenocopy—Reply
Authors: Mark Heckle, Shadwan Alsafwah, Manyoo Agarwal
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
Abstract 11520: Defective Cardiac Natriuretic Peptide Signaling Leads to Lactation-induced Postpartum Cardiomyopathy
Authors: Kentaro Otani, Takeshi Tokudome, Ichiro Kishimoto, Yuanjie Mao, Kenichi Yamahara, Kenji Kangawa, Tomoaki Ikeda
Journal: Circulation (2012)

Volume overload during pregnancy results in transient and reversible cardiac hypertrophy in pregnant females. Endogenous atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) acts th...
Cosensitization to profilin is associated with less severe reactions to foods in ns<scp>LTP</scp>s and storage proteins reactors and with less severe respiratory allergy
Authors: E. Scala, D. Abeni, E. C. Guerra, M. Locanto, L. Pirrotta, G. Meneguzzi, M. Giani, R. Asero
Journal: Allergy (2018)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Gene therapy and genome surgery in the retina
Authors: James E. DiCarlo, Vinit B. Mahajan, Stephen H. Tsang
Journal: Journal of Clinical Investigation (2018)

Precision medicine seeks to treat disease with molecular specificity. Advances in genome sequence analysis, gene delivery, and genome surgery have allowed clinician-scientists to treat genetic conditions at the level of their pathology. As a result, progress in treating retinal disease using genetic tools has advanced tremendously over the past several decades. Breakthroughs in gene delivery vectors, both viral and nonviral, have allowed the delivery of genetic payloads in preclinical models of retinal disorders and have paved the way for numerous successful clinical trials. Moreover, the adaptation of CRISPR-Cas systems for genome engineering have enabled the correction of both recessive and dominant pathogenic alleles, expanding the disease-modifying power of gene therapies. Here, we highlight the translational progress of gene therapy and genome editing of several retinal disorders, including RPE65-, CEP290-, and GUY2D-associated Leber congenital amaurosis, as well as choroideremia, achromatopsia, Mer tyrosine kinase– (MERTK–) and RPGR X-linked retinitis pigmentosa, Usher syndrome, neovascular age-related macular degeneration, X-linked retinoschisis, Stargardt disease, and Leber hereditary optic neuropathy.
Association of Medical Liability Reform With Clinician Approach to Coronary Artery Disease Management
Authors: Steven A. Farmer, Ali Moghtaderi, Samantha Schilsky, David Magid, William Sage, Nori Allen, Frederick A. Masoudi, Avi Dor, Bernard Black
Journal: JAMA Cardiology (2018)

Physicians often report practicing defensive medicine to reduce malpractice risk, including performing expensive but marginally beneficial tests and procedures. Although there is little evidence that malpractice reform affects overall health care spending, it may influence physician behavior for specific conditions involving clinical uncertainty.To examine whether reducing malpractice risk is associated with clinical decisions involving coronary artery disease testing and treatment.Difference-in-differences design, comparing physician-specific changes in coronary artery disease testing and treatment in 9 new-cap states that adopted damage caps between 2003 and 2005 with 20 states without caps. We used the 5% national Medicare fee-for-service random sample between 1999 and 2013. Physicians (n = 75 801; 36 647 in new-cap states) who ordered or performed 2 or more coronary angiographies. Data were analyzed from June 2015 to January 2018.Changes in ischemic evaluation rates for possible coronary artery disease, type of initial evaluation (stress testing or coronary angiography), progression from stress test to angiography, and progression from ischemic evaluation to revascularization (percutaneous coronary intervention or coronary artery bypass grafting).We studied 36 647 physicians in new-cap states and 39 154 physicians in no-cap states. New-cap states had younger populations, more minorities, lower per-capita incomes, fewer physicians per capita, and lower managed care penetration. Following cap adoption, new-cap physicians reduced invasive testing (angiography) as a first diagnostic test compared with control physicians (relative change, -24%; 95% CI, -40% to -7%; P = .005) with an offsetting increase in noninvasive stress testing (7.8%; 95% CI, -3.6% to 19.3%; P = .17), and referred fewer patients for angiography following stress testing (-21%; 95% CI, -40% to -2%; P = .03). New-cap physicians also reduced revascularization rates after ischemic evaluation (-23%; 95% CI, -40% to -4%; P = .02; driven by fewer percutaneous coronary interventions). Changes in overall ischemic evaluation rates were similar for new-cap and control physicians (-0.05%; 95% CI, -8.0% to 7.9%; P = .98).Physicians substantially altered their approach to coronary artery disease testing and follow-up after initial ischemic evaluations following adoption of damage caps. They performed a similar number of ischemic evaluations but conducted fewer initial left heart catheterizations, referred fewer stress-tested patients for left heart catheterizations, and referred fewer patients for revascularization. These findings suggest that physicians tolerate greater clinical uncertainty in coronary artery disease testing and treatment if they face lower malpractice risk.
Letter by Hernandez-Gonzalez et al Regarding Article, “Phenotypic Characterization of <i>EIF2AK4</i> Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension”
Authors: Ignacio Hernandez-Gonzalez, Paula Navas, Pilar Escribano-Subias
Journal: Circulation (2018)