tbuckley/cabot-search huggingface dataset:
Gene Expression Assays to Tailor Adjuvant Endocrine Therapy for HR+/HER2− Breast Cancer
Authors: Michele Bottosso, Federica Miglietta, Grazia Maria. Vernaci, Tommaso Giarratano, Maria Vittoria Dieci, Valentina Guarneri, Gaia Griguolo
Journal: Clinical Cancer Research (2024)

Adjuvant endocrine therapy (ET) represents the standard of care for almost all hormone receptor (HR)+/HER2- breast cancers, and different agents and durations are currently available. In this context, the tailoring and optimization of adjuvant endocrine treatment by reducing unnecessary toxic treatment while taking into account the biological heterogeneity of HR+/HER2- breast cancer represents a clinical priority. There is therefore a significant need for the integration of biological biomarkers in the choice of adjuvant ET beyond currently used clinicopathological characteristics. Several gene expression assays have been developed to identify patients with HR+/HER2- breast cancer who will not derive benefit from the addition of adjuvant chemotherapy. By enhancing risk stratification and predicting therapeutic response, genomic assays have also shown to be a promising tool for optimizing endocrine treatment decisions. In this study, we review evidence supporting the use of most common commercially available gene expression assays [Oncotype DX, MammaPrint, Breast Cancer Index (BCI), Prosigna, and EndoPredict] in tailoring adjuvant ET. Available data on the use of genomic tests to inform extended adjuvant treatment choice based on the risk of late relapse and on the estimated benefit of a prolonged ET are discussed. Moreover, preliminary evidence regarding the use of genomic assays to inform de-escalation of endocrine treatment, such as shorter durations or omission, for low-risk patients is reviewed. Overall, gene expression assays are emerging as potential tools to further personalize adjuvant treatment for patients with HR+/HER2- breast cancers.
Patients’ and dermatologists’ preferences in artificial intelligence–driven skin cancer diagnostics: A prospective multicentric survey study
Authors: Sarah Haggenmüller, Roman C. Maron, Achim Hekler, Eva Krieghoff-Henning, Jochen S. Utikal, Maria Gaiser, Verena Müller, Sascha Fabian, Friedegund Meier, Sarah Hobelsberger, Frank F. Gellrich, Mildred Sergon, Axel Hauschild, Michael Weichenthal, Lars E. French, Lucie Heinzerling, Justin G. Schlager, Kamran Ghoreschi, Max Schlaak, Franz J. Hilke, Gabriela Poch, Sören Korsing, Carola Berking, Markus V. Heppt, Michael Erdmann, Sebastian Haferkamp, Konstantin Drexler, Dirk Schadendorf, Wiebke Sondermann, Matthias Goebeler, Bastian Schilling, Jakob N. Kather, Stefan Fröhling, Katharina Kaminski, Astrid Doppler, Tabea Bucher, Titus J. Brinker, Carina Nogueira Garcia, Janis Thamm, Sandra Schuh, Julia Welzel, Lara Valeska Maul-Duwendag, Paul Georg, Laurence Feldmeyer, Falk Bechara, Julian Steininger, Sophia Lehr, Ricarda Rauschenberg, Anna-Lisa Eberle, Sören Manfred Hartmann, Helena Hasler, Sophia Bender-Säbelkampf, Jürgen P. Bauerschmitz, Matthias Kaufmann, Cornelia Erfurt-Berge, Wiebke Katharina Peitsch, Ulrike Wehkamp, Marion Jost, Cindy Franklin, Julia Holzgruber, Maximilian Haist, Mario Giulini, Sebastian Wohlfeil, Valentina Faihs, Elke Sattler, Suzan Stürmer, Sebastian Krammer, Benjamin Kendziora, Semra Larissa Akcetin, Mohammed Mitwalli, Pinar Avci, Zeno Fiocco, Daniela Hartmann, Manuel Pedro Fernandes Lobo Pereira, Alexander Thiem, Valentin Aebischer, Stephan Forchhammer, Isabel Wolff
Journal: Journal of the American Academy of Dermatology (2024)
Plasma Proteins Associated with Chronic Histopathologic Lesions on Kidney Biopsy
Authors: Taesoo Kim, Aditya L. Surapaneni, Insa M. Schmidt, Michael T. Eadon, Sahir Kalim, Anand Srivastava, Ragnar Palsson, Isaac E. Stillman, Jeffrey B. Hodgin, Rajasree Menon, Edgar A. Otto, Josef Coresh, Morgan E. Grams, Sushrut S. Waikar, Eugene P. Rhee
Journal: Journal of the American Society of Nephrology (2024)

Key Points Proteomic profiling identified 35 blood proteins associated with chronic histopathologic lesions in the kidney. Testican-2 was expressed in the glomerulus, released by the kidney into circulation, and inversely associated with glomerulosclerosis severity. NELL1 was expressed in tubular epithelial cells, released by the kidney into circulation, and inversely associated with interstitial fibrosis and tubular atrophy severity. Background The severity of chronic histopathologic lesions on kidney biopsy is independently associated with higher risk of progressive CKD. Because kidney biopsies are invasive, identification of blood markers that report on underlying kidney histopathology has the potential to enhance CKD care. Methods We examined the association between 6592 plasma protein levels measured by aptamers and the severity of interstitial fibrosis and tubular atrophy (IFTA), glomerulosclerosis, arteriolar sclerosis, and arterial sclerosis among 434 participants of the Boston Kidney Biopsy Cohort. For proteins significantly associated with at least one histologic lesion, we assessed renal arteriovenous protein gradients among 21 individuals who had undergone invasive catheterization and assessed the expression of the cognate gene among 47 individuals with single-cell RNA sequencing data in the Kidney Precision Medicine Project. Results In models adjusted for eGFR, proteinuria, and demographic factors, we identified 35 proteins associated with one or more chronic histologic lesions, including 20 specific for IFTA, eight specific for glomerulosclerosis, and one specific for arteriolar sclerosis. In general, higher levels of these proteins were associated with more severe histologic score and lower eGFR. Exceptions included testican-2 and NELL1, which were associated with less glomerulosclerosis and IFTA, respectively, and higher eGFR; notably, both of these proteins demonstrated significantly higher levels from artery to renal vein, demonstrating net kidney release. In the Kidney Precision Medicine Project, 13 of the 35 protein hits had cognate gene expression enriched in one or more cell types in the kidney, including podocyte expression of select glomerulosclerosis markers (including testican-2) and tubular expression of several IFTA markers (including NELL1). Conclusions Proteomic analysis identified circulating proteins associated with chronic histopathologic lesions, some of which had concordant site-specific expression within the kidney.
Grainyhead-like 2 Deficiency and Kidney Cyst Growth in a Mouse Model
Authors: Zeliha Yesim Yurtdas, Ergin Kilic, Peter Boor, Emanuel Wyler, Markus Landthaler, Klaus Jung, Kai M. Schmidt-Ott
Journal: Journal of the American Society of Nephrology (2024)

Key Points Our study reveals segment-specific mechanisms in cystic kidney disease and suggests Grhl2 as a modifier of collecting duct–derived cyst progression. Our data demonstrate that genetic deletion of Grhl2 accelerates disease progression in a cystic mouse model. Background The transcription factor grainyhead-like 2 (GRHL2) plays a crucial role in maintaining the epithelial barrier properties of the kidney collecting duct and is important to osmoregulation. We noticed a reduction in GRHL2 expression in cysts derived from the collecting ducts in kidneys affected by autosomal dominant polycystic kidney disease (ADPKD). However, the specific role of GRHL2 in cystic kidney disease remains unknown. Methods The functional role of the transcription factor Grhl2 in the context of cystic kidney disease was examined through analysis of its expression pattern in patient samples with ADPKD and generating a transgenic cystic kidney disease (TCKD) mouse model by overexpressing the human proto-oncogene c-MYC in kidney collecting ducts. Next, TCKD mice bred with collecting duct–specific Grhl2 knockout mice (Grhl2KO). The resulting TCKD- Grhl2 KO mice and their littermates were examined by various types of histological and biochemical assays and gene profiling analysis through RNA sequencing. Results A comprehensive examination of kidney samples from patients with ADPKD revealed GRHL2 downregulation in collecting duct–derived cyst epithelia. Comparative analysis of TCKD and TCKD- Grhl2 KO mice exhibited that the collecting duct–specific deletion of Grhl2 resulted in markedly aggravated cyst growth, worsened kidney dysfunction, and shortened life span. Furthermore, transcriptomic analyses indicated sequential downregulation of kidney epithelial cyst development regulators ( Frem2 , Muc1 , Cdkn2c , Pkd2 , and Tsc1 ) during cyst progression in kidneys of TCKD- Grhl2 KO mice, which included presumed direct Grhl2 target genes. Conclusions These results suggest Grhl2 as a potential progression modifier, especially for cysts originating from collecting ducts.
The efficacy and safety of stereotactic body radiotherapy combined with systematic therapy for metastatic renal cell carcinoma: a systematic review and meta‐analysis
Authors: Shiyu Zhang, Xingyu Xiong, Nan Xie, Weitao Zheng, Yongjun Li, Tianhai Lin, Qiang Wei, Ping Tan
Journal: MedComm (2024)

Abstract There is considerable interest in the potential of stereotactic body radiation therapy (SBRT) combined with systemic therapy such as tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs). However, its efficacy and safety remain unclear. The purpose of this study was to evaluate the efficacy and safety of conducting SBRT during ICI or TKI treatment in different disease settings for patients with metastatic renal cell carcinoma (mRCC). A total of 16 studies were ultimately included. Under the random effects model, the pooled 1‐year local control rate (1‐yr LCR) and objective response rate (ORR) were 90% (95% confidence interval [CI]: 80%–95%, I 2 = 67%) and 52% (95% CI: 37%–67%, I 2 = 90%), respectively. SBRT concomitant with different systemic therapy yield significant different 1‐yr LCR ( p &lt; 0.01) and ORR ( p = 0.02). Regarding survival benefits, the pooled 1‐year progression‐free survival (1‐yr PFS) and 1‐year overall survival (1‐yr OS) rates were 45% (95% CI: 29%–62%, I 2 = 91%) and 85% (95% CI: 76%–91%, I 2 = 66%), respectively. 1‐yr PFS and 1‐yr OS in different disease settings demonstrated significant difference ( p &lt; 0.01). As for toxicity, the pooled incidence of grade 3–4 adverse events was 14% (95% CI: 5%–26%, I 2 = 90%). This study highlights the feasibility of utilizing these strategies in mRCC patients, especially those with a low metastatic tumor burden.
Reversals in the Decline of Heart Failure Mortality in the US, 1999 to 2021
Authors: Ahmed Sayed, Dmitry Abramov, Gregg C. Fonarow, Mamas A. Mamas, Ofer Kobo, Javed Butler, Marat Fudim
Journal: JAMA Cardiology (2024)

This cohort study evaluates recent reversals in declines in cardiovascular mortality and whether they vary across sociodemographic categories.
Magnetic Seizure Therapy vs Electroconvulsive Therapy for Major Depressive Episode
Authors: William V. McCall, Mark S. George, Harold A. Sackeim
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Staffing and Antipsychotic Medication Use in Nursing Homes and Neighborhood Deprivation
Authors: Jasmine L. Travers, Erinn M. Hade, Steven Friedman, Aasha Raval, Kimberly Hadson, Jason R. Falvey
Journal: JAMA Network Open (2024)

Importance Inappropriate use of antipsychotic medications in nursing homes is a growing public health concern. Residents exposed to higher levels of socioeconomic deprivation in the area around a nursing home may be currently exposed, or have a long history of exposure, to more noise pollution, higher crime rates, and have less opportunities to safely go outside the facility, which may contribute to psychological stress and increased risk of receiving antipsychotic medications inappropriately. However, it is unclear whether neighborhood deprivation is associated with use of inappropriate antipsychotic medications and whether this outcome is different by facility staffing levels. Objective To evaluate whether reported inappropriate antipsychotic medication use differs in severely and less severely deprived neighborhoods, and whether these differences are modified by higher levels of total nurse staffing. Design, Setting, and Participants This was a cross-sectional analysis of a national sample of nursing homes that linked across 3 national large-scale data sets for the year 2019. Analyses were conducted between April and June 2023. Exposure Neighborhood deprivation status (severe vs less severe) and total staffing hours (registered nurse, licensed practical nurse, certified nursing assistant). Main Outcome and Measures This study estimated the association between neighborhood deprivation and the percentage of long-stay residents who received an antipsychotic medication inappropriately in the nursing home at least once in the past week and how this varied by nursing home staffing through generalized estimating equations. Analyses were conducted on the facility level and adjusted for state fixed effects. Results This study included 10 966 nursing homes (1867 [17.0%] in severely deprived neighborhoods and 9099 [83.0%] in less deprived neighborhoods). Unadjusted inappropriate antipsychotic medication use was greater in nursing homes located in severely deprived neighborhoods (mean [SD], 15.9% [10.7%] of residents) than in those in less deprived neighborhoods (mean [SD], 14.2% [8.8%] of residents). In adjusted models, inappropriate antipsychotic medication use was higher in severely deprived neighborhoods vs less deprived neighborhoods (19.2% vs 17.1%; adjusted mean difference, 2.0 [95% CI, 0.35 to 3.71] percentage points) in nursing homes that fell below critical levels of staffing (less than 3 hours of nurse staffing per resident-day). Conclusions and Relevance These findings suggest that levels of staffing modify disparities seen in inappropriate antipsychotic medication use among nursing homes located in severely deprived neighborhoods compared with nursing homes in less deprived neighborhoods. These findings may have important implications for improving staffing in more severely deprived neighborhoods.
The Diagnosis of Cancer After Recent Weight Loss—Reply
Authors: Qiao-Li Wang, Chen Yuan, Brian M. Wolpin
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Neurodevelopmental Outcomes After Late Preterm Antenatal Corticosteroids
Authors: Cynthia Gyamfi-Bannerman, Rebecca G. Clifton, Alan T. N. Tita, Sean C. Blackwell, Monica Longo, Jessica A. de Voest, T. Michael O’Shea, Sabine Z. Bousleiman, Felecia Ortiz, Dwight J. Rouse, Torri D. Metz, George R. Saade, Kara M. Rood, Kent D. Heyborne, John M. Thorp, Geeta K. Swamy, William A. Grobman, Kelly S. Gibson, Yasser Y. El-Sayed, George A. Macones
Journal: JAMA (2024)

The Antenatal Late Preterm Steroids (ALPS) trial changed clinical practice in the United States by finding that antenatal betamethasone at 34 to 36 weeks decreased short-term neonatal respiratory morbidity. However, the trial also found increased risk of neonatal hypoglycemia after betamethasone. This follow-up study focused on long-term neurodevelopmental outcomes after late preterm steroids. To evaluate whether administration of late preterm (34-36 completed weeks) corticosteroids affected childhood neurodevelopmental outcomes. Prospective follow-up study of children aged 6 years or older whose birthing parent had enrolled in the multicenter randomized clinical trial, conducted at 13 centers that participated in the Maternal-Fetal Medicine Units (MFMU) Network cycle from 2011-2016. Follow-up was from 2017-2022. Twelve milligrams of intramuscular betamethasone administered twice 24 hours apart. The primary outcome of this follow-up study was a General Conceptual Ability score less than 85 (-1 SD) on the Differential Ability Scales, 2nd Edition (DAS-II). Secondary outcomes included the Gross Motor Function Classification System level and Social Responsiveness Scale and Child Behavior Checklist scores. Multivariable analyses adjusted for prespecified variables known to be associated with the primary outcome. Sensitivity analyses used inverse probability weighting and also modeled the outcome for those lost to follow-up. Of 2831 children, 1026 enrolled and 949 (479 betamethasone, 470 placebo) completed the DAS-II at a median age of 7 years (IQR, 6.6-7.6 years). Maternal, neonatal, and childhood characteristics were similar between groups except that neonatal hypoglycemia was more common in the betamethasone group. There were no differences in the primary outcome, a general conceptual ability score less than 85, which occurred in 82 (17.1%) of the betamethasone vs 87 (18.5%) of the placebo group (adjusted relative risk, 0.94; 95% CI, 0.73-1.22). No differences in secondary outcomes were observed. Sensitivity analyses using inverse probability weighting or assigning outcomes to children lost to follow-up also found no differences between groups. In this follow-up study of a randomized clinical trial, administration of antenatal corticosteroids to persons at risk of late preterm delivery, originally shown to improve short-term neonatal respiratory outcomes but with an increased rate of hypoglycemia, was not associated with adverse childhood neurodevelopmental outcomes at age 6 years or older.
Incisional Wound Irrigation for the Prevention of Surgical Site Infection
Authors: Hannah Groenen, Nathan Bontekoning, Hasti Jalalzadeh, Dennis R. Buis, Yasmine E. M. Dreissen, Jon H. M. Goosen, Haitske Graveland, Mitchel Griekspoor, Frank F. A. IJpma, Maarten J. van der Laan, Roald R. Schaad, Patrique Segers, Wil C. van der Zwet, Ricardo G. Orsini, Anne M. Eskes, Niels Wolfhagen, Stijn W. de Jonge, Marja A. Boermeester
Journal: JAMA Surgery (2024)

Importance Surgical site infections (SSIs) are common postoperative complications and associated with significant morbidity, mortality, and costs. Prophylactic intraoperative incisional wound irrigation is used to reduce the risk of SSIs, and there is great variation in the type of irrigation solutions and their use. Objective To compare the outcomes of different types of incisional prophylactic intraoperative incisional wound irrigation for the prevention of SSIs in all types of surgery. Data Sources PubMed, Embase, CENTRAL, and CINAHL databases were searched up to June 12, 2023. Study Selection Included in this study were randomized clinical trials (RCTs) comparing incisional prophylactic intraoperative incisional wound irrigation with no irrigation or comparing irrigation using different types of solutions, with SSI as a reported outcome. Studies investigating intracavity lavage were excluded. Data Extraction and Synthesis This systematic review and network meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Two reviewers independently extracted the data and assessed the risk of bias within individual RCTs using the Cochrane Risk of Bias 2 tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. A frequentist network meta-analysis was conducted, and relative risks (RRs) with corresponding 95% CIs were reported. Main Outcome and Measure The primary study outcome was SSI. Results A total of 1587 articles were identified, of which 41 RCTs were included in the systematic review, with 17 188 patients reporting 1328 SSIs, resulting in an overall incidence of 7.7%. Compared with no irrigation, antiseptic solutions (RR, 0.60; 95% CI, 0.44-0.81; high level of certainty) and antibiotic solutions (RR, 0.46; 95% CI, 0.29-0.73; low level of certainty) were associated with a beneficial reduction in SSIs. Saline irrigation showed no statistically significant difference compared with no irrigation (RR, 0.83; 95% CI, 0.63-1.09; moderate level of certainty). Conclusions and Relevance This systematic review and network meta-analysis found high-certainty evidence that prophylactic intraoperative incisional wound irrigation with antiseptic solutions was associated with a reduction in SSIs. It is suggested that the use of antibiotic wound irrigation be avoided due to the inferior certainty of evidence for its outcome and global antimicrobial resistance concerns.
Stigmatization and Mental Health Impact of Chronic Pediatric Skin Disorders
Authors: Amy S. Paller, Stephanie M. Rangel, Sarah L. Chamlin, Aleena Hajek, Sheshanna Phan, Marcia Hogeling, Leslie Castelo-Soccio, Irene Lara-Corrales, Lisa Arkin, Leslie P. Lawley, Tracy Funk, Fabiana Castro Porto Silva Lopes, Richard J. Antaya, Michele L. Ramien, Karina L. Vivar, Joyce Teng, Carrie C. Coughlin, Wingfield Rehmus, Deepti Gupta, Lionel Bercovitch, Sarah L. Stein, Christina Boull, Wynnis L. Tom, Marilyn G. Liang, Raegan Hunt, Minnelly Luu, Kristen E. Holland, Jennifer J. Schoch, David Cella, Jin-Shei Lai, James W. Griffith
Journal: JAMA Dermatology (2024)

Chronic skin disorders in children frequently are visible and can cause stigmatization. However, the extent of stigmatization from chronic skin disease and association with mental health needs further study.