tbuckley/cabot-search huggingface dataset:
Impact of CYP2D6 polymorphisms on adverse events in patients with breast cancer treated with tamoxifen: Insights from an early dose escalation trial in CYP2D6 poor metabolizers.
Authors: Isabel Blancas, Eduardo Martínez-De Dueñas, Fernando Rodríguez-Serrano
Journal: Journal of Clinical Oncology (2024)

547 Background: Tamoxifen is widely used in treating hormone receptor-positive breast cancer. It is primarily metabolized by the CYP2D6 enzyme to yield active metabolites. However, CYP2D6 polymorphisms have been associated with a differential response to tamoxifen. In a clinical trial involving an early dose escalation of tamoxifen in poor metabolizers, we found endoxifen concentration levels similar to those of patients with extensive phenotype, and no long-term survival differences among CYP2D6 phenotypes. However, the impact of that dose escalation on side effect incidence was not addressed. Methods: In this study, we analyzed the incidence of specific side effects - osteoarticular pain, hot flashes, asthenia, and uterine alterations - in 86 breast cancer patients, differentiated by their CYP2D6 phenotype estimated according to the Clinical Pharmacogenetics Implementation Consortium. In poor metabolizers, the tamoxifen standard dose of 20 mg/day was escalated to 40 mg/day and 60 mg/day for 4 months each, and then treated with 20 mg/day until completing the treatment. Kaplan-Meier analysis and Cox proportional hazards regression model were employed to assess the relationship between the CYP2D6 phenotype and the incidence of these side effects. Results: The median follow-up time was 139.5 months. The analyses revealed that only uterine changes showed significant differences between CYP2D6 phenotypes, with a lower incidence in extensive metabolizers (P-value &lt; 0.001 in Kaplan-Meier; HR in Cox of 0.195, 95% CI 0.073 - 0.521, P = 0.001). This finding persisted after adjustment for the covariates tumor grade, size, nodal status, chemotherapy, and radiotherapy in multivariate Cox regression (HR 0.098, 95% CI 0.020 - 0.466, P = 0.004). Selection of a subgroup through Propensity Score Matching (21 vs 21) corroborated these results. The spectrum of uterine changes and pathologies included endometrial hyperplasia, polyps, adenocarcinoma, myometrial or endometrial thickening, and the presence of multiple myomas. Conclusions: Our study indicates that an early increase in tamoxifen dose in poor metabolizer patients according to CYP2D6 polymorphisms may significantly affect the incidence of uterine changes, but not the incidence of osteoarticular pain, hot flashes, or asthenia. Clinical trial information: 2007-002942-40/ES .
Evolution and prognostic significance of HER-2 changes from primary to residual disease in patients with HER-2–negative breast cancer receiving neoadjuvant chemotherapy.
Authors: Xi Chen, Lei ji, Xiaoyan Qian, Min Xiao, Qing Li, Qiao Li, Jiayu Wang, Ying Fan, Yang Luo, Fei Ma, Binghe Xu, Pin Zhang
Journal: Journal of Clinical Oncology (2024)

583 Background: HER-2 changes during the neoadjuvant chemotherapy has not been thoroughly evaluated. The current study aimed to analyze the HER-2 status changes from primary to residual disease in HER-2 negative patients after neoadjuvant chemotherapy and evaluate its impact in survival outcomes. Methods: HER-2 negative breast cancer patients with residual disease after NACT who had paired pre- and post-therapeutic HER2 testing results were retrospectively analyzed. Data on clinical and pathological characteristics, treatment information, and survival outcomes were collected for all eligible patients. HER2 changes from the primary to residual disease were described and logistic regression were performed to identify factors associated with HER2 changes. The Kaplan–Meier method and multivariate Cox regression were used for survival analysis. Results: 571 HER-2 negative breast cancer patients with residual disease after NACT were enrolled, including HER2-zero (35.2%, n=201) and HER2-low (64.8%, n=370) patients before NAC. The overall rate of HER-2 changes rate was 32.4% (negative to positive 1.1%, low to zero 15.4%, zero to low 15.9%). Among the patients with HER-2-zero before NAC, patients with HER-2 changes (zero to low) were likely to be hormone receptor positive (68.1% vs 36.7%, P&lt;0.0001) and had a higher proportion of patients with Ki-67≤20 (Ki-67≤20 27.5% vs 15.6%, P=0.035). Among the patients with HER2-low before NAC, a higher proportion of hormone receptor negative were observed in HER2 changes patients (low to zero) (31.8% vs 18.4%, P=0.008) and the Ki-67 is relatively high in HER-2 changes patients (Ki-76 &gt; 20 73.9% vs 65.0% P=0.030). Multivariable logistic regression analyses showed patients with hormone receptor positive before NAC were related to underwent HER2-zero transferring to HER2-low (OR, 3.436, P&lt;0.0001). The median follow-up time was 50.0 months. In the HER-2 zero group, HER2 changes (zero to low) was significantly associated with better DFS comparing with constant HER2-zero (HR0.49, P=0.01) after adjustment, with 4-year DFS rate was 80.1%,55.7% (Log-rank P =0.033). Subgroup analysis showed that in the hormone receptor positive subgroup, patients with HER2 zero to low has a significant better DFS than patients with constant HER2-zero (Log-rank P=0.037). In the HER2-low group, no significant differences in survival outcomes between constant HER2-low and HER2 low to zero (HR1.07, P=0.778). Conclusions: HER2 status showed instability from primary tumor to residual disease after neoadjuvant treatment. HER2 changes (zero to low) was associated with better DFS in HER-2 zero patients.
Cost consequence model of the MammaPrint (70-gene signature) and 21-gene signature in patients with primary HR+HER2-, N1 early-stage breast cancer in Germany.
Authors: Michael Patrick Lux, Mariana Felicia Sandor, Viktoria Hofman, Lotta Ada Fischer, Sherko Kuemmel, Darina Pronin, Jelle Klinkhamer, Harald Mueller-Huesmann
Journal: Journal of Clinical Oncology (2024)

534 Background: The MammaPrint 70-gene and Oncotype DX 21-gene signatures serve to stratify breast cancer tumors, distinguishing between those with low or high risk of distant metastasis. Patients with a low genomic risk tumor have the option to avoid overtreatment by omitting chemotherapy and minimize associated toxicities. This analysis evaluates the economic impact of implementing MammaPrint, Oncotype DX (ODx), or no gene signature testing for patients with HR+ HER2- early breast cancer with 1 to 3 positive lymph nodes (N1) in Germany. Methods: We constructed a cost-consequence model to assess the budget implications of MammaPrint, ODx, and not employing a gene signature, considering both the healthcare payers and societal perspective. The model focuses on patients with HR+/HER2-/N1 breast tumors who, in the absence of a gene expression analysis, would receive chemotherapy in 63% of cases according to the data of the certified breast cancers in Germany. Input data were sourced from MINDACT, RxPONDER, literature, the EBM, the DRG system. The healthcare payer perspective covers testing, direct/indirect costs of chemotherapy, and disease recurrence costs. The societal perspective adds transport costs and productivity losses to these. Results: A projected 9,207 HR+/HER2-/N1 breast cancer patients were candidates for genomic testing. In MINDACT, patients were classified as MammaPrint Low Risk in 73% of cases, and in RxPONDER 83% of patients were categorized as ODx Low Risk (RS 0-25). The model demonstrated per patient savings from a healthcare payer perspective of €3.766 for MammaPrint and €900 for ODx compared to not using any gene signature for N1 breast cancer patients in Germany. Importantly, the savings are even more substantial from a societal perspective, reaching €11.815 for MammaPrint and €11.243 for ODx. When limiting the population to women &gt;50 years, similar results were observed with per patient savings from a payer perspective of €3.766 and €1.549, and from a societal perspective of €9.826 and €9.349, for MammaPrint and ODx, respectively. Conclusions: These data demonstrate that personalized treatment planning with genomic testing for breast cancer with HR+/HER2-/LN1 breast cancer, leads to a reduction in chemotherapy use and associated costs in Germany. Although MammaPrint designates a smaller proportion of genomically high risk patients compared to ODx, MammaPrint Low Risk patients without chemotherapy demonstrate higher survival outcomes. Consequently, any increased chemotherapy costs are offset by lower testing and distant recurrence expenses, making MammaPrint a cost-conscious option.
ChatGPT<i>versus</i>Bing: a clinician assessment of the accuracy of AI platforms when responding to COPD questions
Authors: Arouba Imtiaz, Joanne King, Steve Holmes, Ayushman Gupta, Mona Bafadhel, Marc L. Melcher, John R. Hurst, Daniel Farewell, Charlotte E. Bolton, Jamie Duckers
Journal: European Respiratory Journal (2024)

Chronic obstructive pulmonary disease (COPD) is a global respiratory challenge ranking third in morbidity and mortality, primarily caused by exposure to particulate matter, notably from tobacco smoke [1, 2]. The resulting inflammation and lung damage can lead to symptoms of symptoms such as shortness of breath, wheezing, cough and sputum production [1]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of Interest: All authors have nothing to disclose.
Genetic predisposition to high BMI increases risk of early life respiratory infections and episodes of severe wheeze and asthma
Authors: Signe Kjeldgaard Jensen, Casper-Emil Tingskov Pedersen, Kasper Fischer-Rasmussen, Mathias Elsner Melgaard, Nicklas Brustad, Julie Nyholm Kyvsgaard, Nilo Vahman, Ann-Marie Malby Schoos, Jakob Stokholm, Bo Chawes, Anders Eliasen, Klaus Bønnelykke
Journal: European Respiratory Journal (2024)

Background High body mass index (BMI) is an established risk factor for asthma, but the underlying mechanisms remain unclear. Objective To increase understanding of the BMI–asthma relationship by studying the association between genetic predisposition to higher BMI and asthma, infections and other asthma traits during childhood. Methods Data were obtained from the two ongoing Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) mother–child cohorts. Polygenic risk scores for adult BMI were calculated for each child. Replication was done in the large-scale register-based Integrative Psychiatric Research (iPSYCH) cohort using data on hospitalisation for asthma and infections. Results In the COPSAC cohorts (n=974), the adult BMI polygenic risk score was significantly associated with lower respiratory tract infections (incidence rate ratio (IRR) 1.20, 95% CI 1.08–1.33, false discovery rate p-value (pFDR)=0.005) at age 0–3 years and episodes of severe wheeze (IRR 1.30, 95% CI 1.06–1.60, pFDR=0.04) at age 0–6 years. Lower respiratory tract infections partly mediated the association between the adult BMI polygenic risk score and severe wheeze (proportion mediated: 0.59, 95% CI 0.28–2.24, p-value associated with the average causal mediation effect (pACME)=2e −16 ). In contrast, these associations were not mediated through the child's current BMI and the polygenic risk score was not associated with an asthma diagnosis or reduced lung function up to age 18 years. The associations were replicated in iPSYCH (n=114 283), where the adult BMI polygenic risk score significantly increased the risk of hospitalisations for lower respiratory tract infections and wheeze or asthma throughout childhood to age 18 years. Conclusion Children with genetic predisposition to higher BMI had increased risk of lower respiratory tract infections and severe wheeze, independent of the child's current BMI. These results shed further light on the complex relationship between body mass BMI and asthma.
Video-based direct observation physiotherapy in children with cystic fibrosis: a randomised controlled trial
Authors: Sheetal Agarwal, Kana Ram Jat, Sumita Gupta, Jhuma Sankar, Rakesh Lodha, S.K. Kabra
Journal: European Respiratory Journal (2024)

Airway clearance therapy (ACT) is integral to management of cystic fibrosis (CF) [1]. Adherence to therapy in patients with CF is generally poor for inhaled medications and ACT as they are time-consuming [2]. The reported adherence rate to ACT ranges from 33% to 91%, and the variation may be due to the differences in parameters used to assess the ACT [3]. However, the "adherence rate with the correct technique" was only 37% in the REACT program [4]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflicts of Interest: There are no conflicts of interest
Chronic Pruritus
Authors: Daniel C. Butler, Timothy Berger, Sarina Elmariah, Brian Kim, Sarah Chisolm, Shawn G. Kwatra, Nicholas Mollanazar, Gil Yosipovitch
Journal: JAMA (2024)

Chronic pruritus, defined as itch experienced for 6 weeks or longer, affects approximately 22% of people in their lifetime. Approximately 1% of physician visits are for the chief concern of chronic pruritus. Chronic pruritus is associated with adverse outcomes, including impaired sleep and reduced quality of life.
<i>Helicobacter pylori</i> Treatment and Gastric Cancer Risk Among Individuals With High Genetic Risk for Gastric Cancer
Authors: Heng-Min Xu, Yuting Han, Zong-Chao Liu, Zhou-Yi Yin, Meng-Yuan Wang, Canqing Yu, Jun-Ling Ma, Dianjianyi Sun, Wei-Dong Liu, Yang Zhang, Tong Zhou, Jing-Ying Zhang, Pei Pei, Ling Yang, Iona Y. Millwood, Robin G. Walters, Yiping Chen, Huaidong Du, Zhengming Chen, Wei-Cheng You, Liming Li, Kai-Feng Pan, Jun Lv, Wen-Qing Li
Journal: JAMA Network Open (2024)

Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown.
Laparoscopic Sentinel Node Navigation Surgery for Quality of Life Gains
Authors: Marion Liu, Vivian Strong
Journal: JAMA Surgery (2024)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 2024 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 Surgery journal
Differential Outcomes of Placebo Treatment Across 9 Psychiatric Disorders
Authors: Tom Bschor, Lea Nagel, Josephine Unger, Guido Schwarzer, Christopher Baethge
Journal: JAMA Psychiatry (2024)

Importance Placebo is the only substance systematically evaluated across common psychiatric diagnoses, but comprehensive cross-diagnostic comparisons are lacking. Objective To compare changes in placebo groups in recent high-quality randomized clinical trials (RCTs) across a broad spectrum of psychiatric disorders in adult patients. Data Sources MEDLINE and the Cochrane Database of Systematic Reviews were systematically searched in March 2022 for the latest systematic reviews meeting predetermined high-quality criteria for 9 major psychiatric diagnoses. Study Selection Using these reviews, the top 10 highest-quality (ie, lowest risk of bias, according to the Cochrane Risk of Bias tool) and most recent placebo-controlled RCTs per diagnosis (totaling 90 RCTs) were selected, adhering to predetermined inclusion and exclusion criteria. Data Extraction and Synthesis Following the Cochrane Handbook, 2 authors independently carried out the study search, selection, and data extraction. Cross-diagnosis comparisons were based on standardized pre-post effect sizes (mean change divided by its SD) for each placebo group. This study is reported following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. Main Outcome and Measure The primary outcome, pooled pre-post placebo effect sizes ( d av ) with 95% CIs per diagnosis, was determined using random-effects meta-analyses. A Q test assessed statistical significance of differences across diagnoses. Heterogeneity and small-study effects were evaluated as appropriate. Results A total of 90 RCTs with 9985 placebo-treated participants were included. Symptom severity improved with placebo in all diagnoses. Pooled pre-post placebo effect sizes differed across diagnoses ( Q = 88.5; df = 8; P &amp;amp;lt; .001), with major depressive disorder ( d av = 1.40; 95% CI, 1.24-1.56) and generalized anxiety disorder ( d av = 1.23; 95% CI, 1.06-1.41) exhibiting the largest d av . Panic disorder, attention-deficit/hyperactivity disorder, posttraumatic stress disorder, social phobia, and mania showed d av between 0.68 and 0.92, followed by OCD ( d av = 0.65; 95% CI, 0.51-0.78) and schizophrenia ( d av = 0.59; 95% CI, 0.41-0.76). Conclusion and Relevance This systematic review and meta-analysis found that symptom improvement with placebo treatment was substantial in all conditions but varied across the 9 included diagnoses. These findings may help in assessing the necessity and ethical justification of placebo controls, in evaluating treatment effects in uncontrolled studies, and in guiding patients in treatment decisions. These findings likely encompass the true placebo effect, natural disease course, and nonspecific effects.
Author Correction: Cicer super-pangenome provides insights into species evolution and agronomic trait loci for crop improvement in chickpea
Authors: Aamir W. Khan, Vanika Garg, Shuai Sun, Saurabh Gupta, Olga Dudchenko, Manish Roorkiwal, Annapurna Chitikineni, Philipp E. Bayer, Chengcheng Shi, Hari D. Upadhyaya, Abhishek Bohra, Chellapilla Bharadwaj, Reyazul Rouf Mir, Kobi Baruch, Bicheng Yang, Clarice J. Coyne, Kailash C. Bansal, Henry T. Nguyen, Gil Ronen, Erez Lieberman Aiden, Erik Veneklaas, Kadambot H. M. Siddique, Xin Liu, David Edwards, Rajeev K. Varshney
Journal: Nature Genetics (2024)

In the version of the article initially published, various numbers in the main text did not match the corresponding data in Table 1 and Supplementary Table 6.In the "Genome assembly and annotation of annual wild Cicer genomes" section, "25,761" was corrected to "25,546" in the sentence "…we predicted an average of 25,546 gene models for each Cicer species"; "23,486" and "29,642" have been corrected to "23,516" and "28,627" in the sentence "The number of genes ranged from 23,516 for C. judaicum to 29,627 for C. reticulatum"; "11,505" has been corrected to "11,590" in the sentence "…and 11,505 ribosomal RNA (rRNA) genes for each Cicer species"; and "1,292" has been corrected to "1,297" in the sentence "…with the highest number recorded for C. reticulatum (1,297)".In the first sentence of the "Graph super-pangenome for Cicer genus and SV genotyping" section, "460, 311" has been amended to "465,535".These corrections have been made in the HTML and PDF versions of the article.
Quality of Life and Nutritional Outcomes of Stomach-Preserving Surgery for Early Gastric Cancer
Authors: Bang Wool Eom, Hong Man Yoon, Young-Woo Kim, Jae-Seok Min, Ji Yeong An, Hoon Hur, Young Joon Lee, Gyu Seok Cho, Young Kyu Park, Mi Ran Jung, Ji Ho Park, Woo Jin Hyung, Sang Ho Jeong, Myeong-Cherl Kook, Mira Han, Byung-Ho Nam, Keun Won Ryu, Seok-Ki Kim, Ji Yoon Rho, Chi Lan Won, Kyoung Lae Kim
Journal: JAMA Surgery (2024)

The Sentinel Node Oriented Tailored Approach (SENORITA) randomized clinical trial evaluated quality of life (QoL) and nutritional outcomes between the laparoscopic sentinel node navigation surgery (LSNNS) and laparoscopic standard gastrectomy (LSG). However, there has been no report on the QoL and nutritional outcomes of patients who underwent stomach-preserving surgery among the LSNNS group.
Revisiting Race and the Benefit of RAS Blockade in Heart Failure
Authors: Li Shen, Matthew M. Y. Lee, Pardeep S. Jhund, Christopher B. Granger, Inder S. Anand, Aldo P. Maggioni, Marc A. Pfeffer, Scott D. Solomon, Karl Swedberg, Salim Yusuf, John J. V. McMurray
Journal: JAMA (2024)

Concerns have arisen that renin-angiotensin system (RAS) blockers are less effective in Black patients than non-Black patients with heart failure and reduced ejection fraction (HFrEF).