tbuckley/cabot-search huggingface dataset:
Correspondence on ‘Re-examining remission definitions in rheumatoid arthritis: considering the 28-joint Disease Activity Score, C reactive protein level and patient global assessment’
Authors: Ricardo J O Ferreira, Paco M J Welsing, Johannes WG Jacobs, Laure Gossec, Mwidimi Ndosi, Pedro M Machado, Désirée van der Heijde, Jose AP Da Silva
Journal: Annals of the Rheumatic Diseases (2022)
Quantifying molecular imaging patterns of treatment response or progression using a novel traffic light workflow within a prospective phase I/II trial of <sup>177</sup>LuPSMA-617 and NOX66 (LuPIN).
Authors: Sarennya Pathmanandavel, Megan Crumbaker, Andrew O. Yam, Andrew Nguyen, Remy Niman, Peter Wilson, Shikha Sharma, Maria Ayers, Peter Eu, Martin R. Stockler, Andrew James Martin, Anthony M. Joshua, Louise Emmett
Journal: Journal of Clinical Oncology (2022)

166 Background: 177 Lutetium PSMA-617 (LuPSMA) is an effective therapy for metastatic castrate-resistant prostate cancer (mCRPC). However, treatment resistance may occur. We developed a quantitative workflow for serial PSMA PET/CT to optimise predictive and prognostic imaging biomarker capability for progression free (PFS) and overall survival (OS). Methods: 56 men with mCRPC previously treated with taxane chemotherapy and androgen signaling inhibitor were enrolled, receiving up to 6 doses of LuPSMA and a radiation sensitizer idronoxil (NOX66). 68 Ga-PSMA-11 PET/CT was performed at study entry and exit. Traffic Light (TL) quantification workflow was developed to track changes in both tumour volume and intensity at a total body and lesional level. Lesions were classified as responding in green (&gt;30% decline in volume), stable in yellow (&lt;30% change in volume/intensity), progressive in red (&gt;30% increase in volume/intensity, or new). Overall response pattern was categorised as responding ( green/yellow), low volume red (&lt;50% progressive disease) or high volume red (&gt;50% progressive disease). TL workflow results were correlated with PFS and OS. Results: 37/56 men underwent both entry and exit imaging. The median PSA decline was 77% (IQR 34-92%), and 70% (26/37) achieved PSA response &gt;50%. PSA progression occurred in 54% (20/37) at exit imaging. Median PFS was 8.6 months (95%CI 5.6-11.6) and median OS 22 months (95% CI 18.6-25.6). 95% (35/37) had reduction in PSMA SUVmax (-26.1 (IQR +11.7 to -89.4)) and SUVmean (-3.3 (+2.9 to -14.2)). PSMA total tumor volume reduced in 68% (25/37) (median -0.64 liters (range +1.44 to -1.1)). On TL workflow, 24% (9/37) had responding/stable disease ( green/ yellow), 76% (28/37) had progressive disease ( red) of whom 41% (15/37) had low volume progression and 35% (13/37) high volume progression. Men with high volume progression had worse OS compared to responders (HR 0.18 (0.05-0.59), p 0.005), and low volume progression (HR 0.30 (0.11-0.80), p 0.02). 68% (19/28) had progression on both TL workflow and PSA, while 32% (9/28) had progression on TL workflow without PSA progression. In multivariable analysis, TL workflow and PSA progression at time of exit scans were independent predictors of OS (Table). Conclusions: This study demonstrates the feasibility of characterizing lesional response on molecular imaging with a quantification TL workflow. TL workflow response independently correlated with survival outcomes, indicating serial PSMA PET has prognostic biomarker potential. Clinical trial information: ACTRN12618001073291.[Table: see text]
Report of the Meeting of the Eastern Branch of the Provincial Association at Bury St. Edmond's
Journal: BMJ (1840)

20th.The patient has been allowed to sit up a few hours to-dav.'llhe stone is globular, somewlhat less than an inch in diameter, of a brown colouir, and its sturface is covered with conical eminences, lhaving an elevation of more than the eighth of an inclh, and giviog the stone somewlhat thte appearanice of a lhorse-chesnuit.At one part there are two parallel lines or belts of these projections; over the re- mainder of the surface they are disposed at irregular distances; the greater tiuimber of them are very muclh pointed; the diameter of the cotnes at thie base is sonme- wlmat less tlian the eiglhth of an inchl.The following woo&i-cut exxhibits the form anid general appearance of the calculus.CATARACT.
Ichthyosis Scoring System—A Powerful Tool in the Era of Immune Pathway–Targeted Therapies for Ichthyosis
Authors: Masashi Akiyama
Journal: JAMA Dermatology (2022)

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 Dermatology 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 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 Dermatology journal
ARTIFICIAL PNEUMOTHORAX
Authors: C. Riviere
Journal: BMJ (1921)

Apparently in this case there is as yet -no evidence of familial affection.The patient lhas several brothers, all younger than himselr, who are healthy.Our reason for reporting this case lies in the fact that myopathy starting in the thiglh muscles and described as the type of Leyden, Moebius, and Zimmerlin is of some rarity.
<i>QuickStats:</i>Age-Adjusted Death Rates,* by Sex — United States, 1979–2014
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

The age-adjusted death rate for the United States declined from 1,010.6 deaths per 100,000 population in 1979 to 724.6 per 100,000 population in 2014, the lowest rate ever recorded.Over the same period, rates for females declined 21.9% from 789.9 to 616.7, while rates for males declined 35.0% from 1,316.2 to 855.1, thus narrowing the mortality gap between males and females.
Targeting resistant prostate cancer, with or without DNA repair defects, using the combination of ceralasertib (ATR inhibitor) and olaparib (the TRAP trial).
Authors: Zachery R Reichert, Michael Edward Devitt, Joshi J. Alumkal, David C. Smith, Megan Veresh Caram, Philip Palmbos, Ulka N. Vaishampayan, Ajjai Shivaram Alva, Thomas Braun, Sarah Elizabeth Yentz, Phoebe A. Tsao, Robert Dreicer, Frank Cameron Cackowski, Neel Shah, Emma Dean, Simon Smith, Elisabeth I. Heath
Journal: Journal of Clinical Oncology (2022)

88 Background: Men with metastatic, castration resistant prostate cancer (mCRPC) harboring DNA repair defects (̃20%) achieve a radiographic progression free survival of 7.4 months with PARP inhibitors (PARPi). Preclinical studies combining a PARPi (olaparib) and DNA damage checkpoint inhibitor (ATR inhibitor, ceralasertib) show synergy, providing the rationale to test this combination in men with mCRPC, including where single agent olaparib has been shown to be active. Methods: Two cohorts were accrued to a trial combining ceralasertib with olaparib in men a) with or b) without DNA repair defects. All patients progressed on ≥1 prior mCRPC therapy with no prior PARPi or platinum chemotherapy. The primary endpoint was disease response (confirmed PSA decline ≥50% and/or RECIST response), while disease progression was defined per Prostate Cancer Working Group 3 definition. Each cohort is analyzed independently for disease endpoints, while both groups were combined for toxicity assessments. Results: The 12 person DNA repair-deficient (DRDef) cohort allowed patients with germline BRCA2 loss (n = 4), somatic BRCA2 loss (n = 1) and ATM loss (n = 1 germline, n = 5 somatic and n = 1 somatic with unknown germline). 35 men without BRCA2/BRCA1 or ATM genomic loss were accrued to the DNA repair-proficient (DRPro) cohort. These men had next-generation sequencing (NGS) on contemporary biopsies (prior to enrolment without intervening therapy, 12), prior NGS on metastatic tissue (10), prior NGS on primary prostatic tissue (n = 3), or cell-free analyses (5). Five patients have incomplete cell-free analyses. At data cutoff (October 2021), in the DRDef cohort, the response rate by confirmed ≥50% PSA decline was 4/10 (40%) including 3 of 4 BRCA2 patients, and another is awaiting sufficient follow up; 1 of 6 ATM-deficient patients responded and another is awaiting sufficient follow up. All 4 DRDef responders remain on therapy (median of 8 months). For patients in the DRPro cohort who have completed therapy and response assessment (n = 21), 3 responded, one with a duration of 12 months, two with 6 months. An updated analysis will be presented. Conclusions: This analysis suggests potential activity of the doublet for DRDef (BRCA2 mainly) and DRPro mCRPC. Ongoing biomarker analysis (e.g. ATM IHC, contemporaneous cell-free DNA analysis rather than archived tissue) may help guide selection of patients most likely to benefit. Clinical trial information: NCT03787680.
CHEMICAL WARFARE AND THE DOCTOR--II
Authors: E. M. Cowell
Journal: BMJ (1939)

<h3>Objective:</h3> Perform an updated characterization of medication utilization among PD patients prescribed levodopa or dopamine agonist (DA) treatments. <h3>Background:</h3> About 1% of individuals age 60+, or 1.5 million persons, are diagnosed with Parkinson’s disease (PD) in the US. Levodopa and DA are most the most common PD treatments. An updated analysis of PD medication use is needed. <h3>Design/Methods:</h3> Retrospective analysis using medical and pharmacy claims data from commercial and Medicare Advantage with Part D (MAPD) insurance enrollees, age 40+ with coverage between 09/01/2011–12/31/2019. Patients had ≥1 claim for levodopa or DA; first claim=index date. Patients had ≥2 PD diagnoses, continuous enrollment for 12 months pre- and post-index, and were excluded if prescribed the index treatment during the pre-index period, or both levodopa and DA on index. Kaplan-Meier analyses estimated time to index treatment discontinuation. <h3>Results:</h3> Patients prescribed levodopa (n=11,125) and DA (n=1,562) differed by age (mean=75 vs. 68 years, p&lt;0.001). The levodopa cohort had higher percentages with MAPD coverage (82.4% vs. 59.8%, p&lt;0.001) and pre-index cognitive decline (12.4% vs. 8.7%, p&lt;0.001). The mean proportion of days covered (medication adherence measure) was higher for levodopa (0.73 vs. 0.61, p&lt;0.001) and a higher percentage of levodopa patients continued index monotherapy throughout the post-index period (81.5% vs. 54.0%, p&lt;0.001). The DA cohort had higher percentages with concomitant treatment (17.6% vs. 5.1%, p&lt;0.001), switched treatment (37.2% vs. 12.9%, p&lt;0.001) and discontinuation (50.3% vs. 35.3%, p&lt;0.001), with shorter mean time to first treatment change (77 days vs. 100, p&lt;0.001). Kaplan-Meier analyses predict the proportion of patients who continued index treatment after 12 months was higher for levodopa patients with commercial (64.4% vs 56.1%, p&lt;0.001) and MAPD (64.8% vs 45.4%, p&lt;0.001) health coverage. <h3>Conclusions:</h3> Results suggest levodopa treatment occurs more consistently than DA treatment, as DA patients had relatively high treatment modification and discontinuation rates, and low medication adherence. <b>Disclosure:</b> Dr. Frazer has received personal compensation for serving as an employee of Optum. Lisa Le has nothing to disclose. Dr. Arcona has received personal compensation for serving as an employee of Cerevel. Dr. Arcona has received stock or an ownership interest from Cerevel. Dr. Sasane has nothing to disclose.
Abstract 144: Differing Pattern of ECG Changes During Resuscitation From Pulseless Electrical Activity Depending on Etiology
Authors: Gunnar W Skjeflo, Trond Nordseth, Jan Pål Loennechen, Daniel Bergum, Eirik Skogvoll
Journal: Circulation (2018)

Introduction: Pulseless electrical activity (PEA) is a frequent initial rhythm in in-hospital cardiac arrest. ECG changes during cardiopulmonary resuscitation (CPR) have been linked to prognosis; QRS complex narrowing and increase in QRS-rate/heart rate was observed before return of spontaneous circulation (ROSC). Our hypothesis was that ECG changes during CPR of patients with cardiac arrest with initial PEA could also be different depending on etiology of arrest. Methods: Patients with cardiac arrest with initial PEA at St. Olav University Hospital (Trondheim, Norway) between January 2009 and January 2012 were prospectively included. QRS duration and heart rate were measured at all pauses in chest compressions. Etiologies were categorized as ‘Cardiac’ or ‘Other’. Trends in the material were inspected using additive mixed effects models for the last 18 minutes before ROSC or end of CPR and development of QRS width was analyzed using linear mixed effects models based on these trends. Results: A total of 63 patients for whom a reliable cause of arrest could be identified retrospectively were included. 1844 combined measurements of QRS width and heart rate were made. According to the additive mixed effects model the development in heart rate was similar in both etiology groups. The change in QRS width differed in patients who obtained ROSC, with the Cardiac group narrowing more than the other group, and both groups ending at essentially the same QRS widths at ROSC (figure). By the linear mixed effects model this difference in change was statistically significant (p=0.04). In patients who did not have ROSC, the cardiac group had significantly (p=0.001, linear mixed effects model) wider QRS complexes, but the change towards ROSC was the same in both groups. Conclusion: During the last 18 minutes before ROSC ECG characteristics differed depending on etiology, with cardiac etiologies having wider QRS complexes in the no-ROSC groups and narrowing more towards ROSC in the ROSC groups.
Cardiovascular Disease Screening in Women: Leveraging Artificial Intelligence and Digital Tools
Authors: Demilade A. Adedinsewo, Amy W. Pollak, Sabrina D. Phillips, Taryn L. Smith, Anna Svatikova, Sharonne N. Hayes, Sharon L. Mulvagh, Colleen Norris, Veronique L. Roger, Peter A. Noseworthy, Xiaoxi Yao, Rickey E. Carter
Journal: Circulation Research (2022)

Cardiovascular disease remains the leading cause of death in women. Given accumulating evidence on sex- and gender-based differences in cardiovascular disease development and outcomes, the need for more effective approaches to screening for risk factors and phenotypes in women is ever urgent. Public health surveillance and health care delivery systems now continuously generate massive amounts of data that could be leveraged to enable both screening of cardiovascular risk and implementation of tailored preventive interventions across a woman’s life span. However, health care providers, clinical guidelines committees, and health policy experts are not yet sufficiently equipped to optimize the collection of data on women, use or interpret these data, or develop approaches to targeting interventions. Therefore, we provide a broad overview of the key opportunities for cardiovascular screening in women while highlighting the potential applications of artificial intelligence along with digital technologies and tools.
Address in Medicine
Authors: F. Sibson
Journal: BMJ (1870)

PRESIDENT AND GENTLE1MENT,-Our age is marked by experiment and exact inquiry, directness of aim, and the skilled power to do the work required of us with completeness and economy.The labour of the past surpassed, but not superseded; and while nothing that has been done is lost; invention awakes invention, discovery discovery.Each advance is a fresh starting point for the future labourer.
Journal of Investigative Dermatology, Baltimore
Journal: JAMA (1967)

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
M2 macrophage increase in prostate adenocarcinoma after high-dose rate brachytherapy.
Authors: Palak Kundu, Nathanael Kane, Andrew Lim, Ting Martin Ma, Yunfeng Li, Rong Rong Huang, Huihui Ye, Alan Lee, Nicholas George Nickols, Albert Chang
Journal: Journal of Clinical Oncology (2022)

271 Background: Brachytherapy delivers high doses of hypofractionated radiation (RT) internally within the prostate tumor. While radiation has been shown to exhibit immunomodulatory effects, the success of combining radiation and immunotherapy in prostate cancer has been limited. M2 macrophages can contribute to an immunosuppressive tumor environment, and we therefore hypothesize that radiation may increase the abundance of M2 macrophage in the prostate tumor immune infiltrate. Methods: 10 Patients with intermediate risk prostate cancer (age 51-78; 7 GS 3+4, 3 GS 4+3) underwent high-dose rate brachytherapy (2 implants, 13.5Gy per implant, 1 week apart). Patients consented to biopsies before each fraction at the first and second implant. Bulk RNA-seq gene expression was performed on formalin-fixed, paraffin-embedded pre- vs. post-RT tumor samples, and then analyzed with a machine learning deconvolution model to resolve immune cell abundances. CD68+CD163+ M2 macrophages were analyzed with multiplex immunohistochemistry and quantified with tissue analysis software. Paired t-test was used to compare M2 macrophage abundance pre- versus post-RT. Results: Bulk RNA-seq deconvolution demonstrated that the most prevalent immune cell types in the pre-RT samples were resting CD4 memory T cells (39.7%), resting mast cells (38.5%), and M2 macrophages (30.4%), while those in the post-RT samples were M2 Macrophages (78.7%), resting mast cells (58.1%), and resting CD4 memory T cells (48%). M2 macrophages demonstrated the greatest increase, which was corroborated by multiplex IHC: average CD68+CD163+ cell counts were significantly elevated after RT (pre-RT 63.7 vs. post-RT 200.1 per mm 2 , p=0.015). Conclusions: Hypofractionated radiation increases the immunosuppressive M2 macrophage population in prostate cancer, which may present a therapeutic target to augment the efficacy of radiation and immunotherapy combinations.
Even common diseases can be complex
Authors: W. R. Barclay
Journal: JAMA (1977)

Frequently we lose sight of the fact that illness is not a matter of just an infection, an injury, a neoplasm, or a metabolic disorder, but of a combination of factors, not the least important of which may be life-style or behavior. Unless the multiple factors underlying an illness are recognized, the diagnosis may be missed or the treatment fail. Such a situation is described in the CLINICAL NOTE in this issue ofThe Journal(p 2718). Fiumara's account of diagnosing gonococcal proctitis in a married woman illustrates once more that the practice of medicine is as much an art as it is a science, and that the securing of a complete and detailed history is an important part of that art. The time constraints of medical practice frequently pressure us into making a hurried diagnosis or instituting a routine form of treatment. Although this approach may suffice for most,
Highlights
Journal: JAMA (2019)

Experimental data suggest that intravenous vitamin C may attenuate infl ammation and vascular injury associated with sepsis and acute respiratory distress syndrome.Fowler and colleagues randomized 167 patients with sepsis and acute respiratory distress syndrome and found that a 96-hour infusion of vitamin C, compared with placebo, did not signifi cantly improve organ dysfunction scores or alter markers of infl ammation and vascular injury.In an Editorial, Brant and Angus suggest that a larger trial could address the dosing and timing of vitamin C for subtypes of patients with sepsis.
A phase 2 study of onvansertib in combination with abiraterone and prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: David Johnson Einstein, Atish Dipankar Choudhury, Philip James Saylor, Jesse Christopher Patterson, Peter Croucher, Maya Ridinger, Mark G. Erlander, Michael B. Yaffe, Glenn Bubley
Journal: Journal of Clinical Oncology (2022)

TPS219 Background: Metastatic CRPC is a leading cause of cancer death worldwide. Although abiraterone (abi) + prednisone in either castration-sensitive or castration-resistant disease increases survival, resistance is universal and generally occurs within 9-16 months of initiating treatment. Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase that regulates mitotic function and is upregulated in prostate cancer following androgen-deprivation therapy (ADT). Onvansertib is an oral and highly-selective PLK1 inhibitor that demonstrated safety and tolerability as a single agent in a Ph1 trial. Preclinical studies showed that PLK1 inhibition enhanced abi anti-tumor effect in cell line models and in patient-derived tumor xenografts via an AR-independent mechanism. Transcriptomic analyses revealed that abi induced mitosis-related gene sets in cells synergistic for abi + onvansertib, and identified an abi-onvansertib synergy gene signature. Methods: The goal of this phase 2 study (NCT03414034) is to observe the effects of onvansertib + abi on disease control, as assessed by prostate-specific antigen (PSA) decline or stabilization after 12 weeks of study treatment, in subjects with mCRPC and early resistance to abi. Patients are enrolled at time of PSA progression while on standard abi. Prior treatment with enzalutamide or apalutamide is not permitted. Three onvansertib dosing schedules are tested in noncomparative arms: arm A (24 mg/m 2 on days 1-5 of a 21-day cycle), arm B (18 mg/m 2 on days 1-5 of a 14-day cycle), and arm C (12 mg/m 2 on days 1-14 of a 21-day cycle). To-date, 24 patients were enrolled in Arm A, and 20 patients each in Arms B and C. With 32 patients in each arm, there will be 90% power to detect a change in disease-control rate from 10% (null) to 30% (alternative). Based on a Simon’s two-stage optimal design, the study will terminate early if &lt; 2 of the first 13 patients in each arm achieve disease control. Exploratory analyses include evaluation of the presence of the androgen receptor variant 7 (AR-V7) in circulating tumor cells and targeted genomic profiling of circulating tumor DNA to assess associations between genomic alterations and response to treatment. Additionally, transcriptomic analysis of archived tumor tissue will be performed to identify gene expression signatures associated with clinical responses. Clinical trial information: NCT03414034.