tbuckley/cabot-search huggingface dataset:
Phase Ib trial of erdafitinib (E) combined with enfortumab vedotin (EV) following platinum and PD-1/L1 inhibitors for metastatic urothelial carcinoma (mUC) with FGFR2/3 genetic alterations (GAs).
Authors: Rohit K. Jain, Youngchul Kim, Jennifer Rembisz, Richard Piekarz, Timothy W. Synold, Jingsong Zhang, Guru P. Sonpavde
Journal: Journal of Clinical Oncology (2022)

TPS595 Background: Erdafitinib and enfortumab vedotin are available treatment options in mUC patients with somatic FGFR2/3 GAs after progression on platinum-based chemotherapy and PD-1/L1 inhibitors. However, due to decline in their clinical condition, the sequential delivery of these agents is challenging. Tubulin antagonists induce a G2-M cell-cycle block, while FGFR inhibitors cause a G1 block, with studies suggesting that their combination may be additive or synergistic. Retrospective studies suggest that the activity of EV is not compromised by somatic FGFR2/3 GAs. Hence, there is rationale to evaluate the feasibility of the combination of EV and E, to overcome the difficulties of resistance and sequencing these agents in mUC patients with FGFR2/3 GAs. Methods: This is a phase Ib, single arm, multicenter study in patients with mUC harboring somatic FGFR2/3 GAs who have progressed after platinum and PD-1/L1 inhibitor therapies with enrollment of up to 30 patients. Pts are required to have predominant urothelial component, ECOG-PS 0-2, neuropathy ≤ grade 1 and no ophthalmologic conditions precluding treatment with E. FGFR2/3 GAs may be identified by tumor tissue or circulating tumor (ct)-DNA profiling. The primary objective is feasibility and establishing a recommended phase-2 dose (RP2D). Secondary objectives include objective response rate, duration of response, progression-free survival and overall survival. The dose-escalation component will enroll up to 18 pts with 3+3 design (dosing cohorts in table), followed by dose-expansion component of 12 pts. The dose limiting toxicities (DLTs) will be evaluated using a sequential Bayesian toxicity monitoring that allows a maximum DLT rate of 0.33 during the dose-expansion phase. Exploratory biomarker analyses will be performed including 1) tumor PD-L1, Nectin-4 assessment by immunohistochemistry and association with response 2) ct-DNA evaluation at baseline and progression to evaluate resistance pathways 3) pharmacokinetic studies will assess plasma levels of E and free monomethyl auristatin-E (MMAE). This is led by North American Star Consortium as part of Experimental Therapeutics. Clinical trial information: NCT04963153. [Table: see text]
Understanding Resistance to Cancer Immunotherapy
Journal: Cancer Discovery (2015)

Abstract New research shows that spontaneous antitumor immunity, which predicts clinical benefit from immune checkpoint inhibitors, is absent in some patients with melanoma due to tumor-intrinsic Wnt/β-catenin signaling. Active β-catenin disrupts CD103+ dendritic cell recruitment, preventing T cells from infiltrating tumors and undermining immunotherapy's effectiveness.
Polyarteritis nodosa.
Authors: C. T. Dollery
Journal: BMJ (1969)

There are few diseases with a more varied clinical picture than polyarteritis nodosa.Any organ may be the first to be affected, and this disease should always be kept in mind in patients who present diagnostic problems, because it can mimic so many other conditions.The aetiology of polyarteritis nodosa is un- known, and diagnosis is complicated by the wide range of other conditions associated with arteritis.These include Wegener's granuloma, lupus erythematosus, rheumatoid arthritis, temporal arteritis, hypersensitivity angiltis, and malignant hypertension.Recently Bywaters1 described a small group of patients with an illness which had many of the clinical features associated with systemic polyarteritis nodosa but no pathological evidence of arteritis.He named this the " Cheshire Cat Syndrome," be- cause-like the cat in Alice in Wonderland, of which only the grin remained-an essential criterion of the disease was missing.Whatever the form of its clinical presentation polyarteritis nodosa usually has a poor prognosis.It is important to make the diagnosis before serious renal damage occurs, because of the possibility that treatment may slow the progression of the disease.
Clinical outcomes in advanced urothelial cancer (UC) patients who experienced immune-related adverse events (irAEs) after immune checkpoint inhibitor monotherapy (ICI).
Authors: Gregory E. Sanda, Julie M. Shabto, Subir Goyal, Yuan Liu, Dylan J. Martini, Bassel Nazha, Jacqueline T Brown, Lauren Beth Yantorni, Greta Russler, Sarah Caulfield, Shreyas S. Joshi, Vikram M. Narayan, Haydn Kissick, Kenneth Ogan, Viraj A. Master, Bradley Curtis Carthon, Omer Kucuk, Mehmet Asim Bilen
Journal: Journal of Clinical Oncology (2022)

544 Background: Immune checkpoint inhibitors (ICIs) continue to demonstrate promise in treatment of advanced urothelial carcinoma (UC). Some patients undergoing ICIs experience immune related adverse events (irAEs) and may serve as a marker of response. We investigated the relationship between irAEs and clinical outcomes in UC patients treated with ICIs. Methods: A retrospective study of 70 UC patients treated with ICI monotherapies at Winship Cancer Institute from 2015-2020 was done. Overall survival (OS) and progression-free survival (PFS), defined as time from ICI initiation to death and clinical or radiographic progression, respectively as well as clinical benefit (CB), defined as best radiographic response of complete response, partial response, or stable disease for ≥ 6 months per RECIST v1.1, were used to measure clinical outcomes. Cox proportional hazards and multivariable analyses (MVA) were used to model associations with OS and PFS. Results: Most patients were male (70%) with a median age of 68.7 years (28.0-91.0). Most patients (95%) had urothelial carcinoma and most (81%) received at least 1 prior treatment. One third of patients had ECOG PS greater than or equal to 2. Of patients that experienced an irAE (35%), the most common were dermatologic (12.9%) and arthralgia (0.5%). In addition to significantly longer treatment duration, irAE patients had significantly increased OS (HR:0.38, 95% CI:0.18-0.79, p=0.009), significantly longer PFS (HR:0.27, 95% CI:0.14-0.53, p &lt; 0.001), and significantly greater CB (OR:4.20, 95% CI:1.35-13.06, p=0.013). Patients who experienced dermatologic irAEs had significantly increased OS, PFS, and CB (Table). Conclusions: Our results demonstrate that UC patients undergoing ICI therapy who experience irAEs, especially dermatologic irAEs, had improved clinical outcomes. This suggests that irAEs may serve as a clinical biomarker of advantageous response in patients receiving ICI. Future prospective studies are needed for validation.[Table: see text]
Medical News
Journal: JAMA (1933)

(Physicians will confer a favor by sending for this department items of news of more or less general interest: such as relate to society activities, new hospitals, education, public health, etc.) <h3>COLORADO</h3><h3>State Medical Meeting at Colorado Springs.</h3> —The sixty-third annual session of the Colorado State Medical Society will be held in Colorado Springs, September 14-16, at the City Auditorium. Dr. Olin West, Chicago, secretary and general manager, American Medical Association, will be the guest speaker at the annual banquet Friday evening, on "Preserving the Professional Aspects of Medical Practice." Guest speakers at the scientific sessions will be: Dr. John Jay Keegan, Omaha, Surgical Indications in Head Injuries. Dr. Claud R. G. Forrester, Chicago, Use of Local Anesthesia in Treatment of Fractures. Dr. Budd C. Corbus, Chicago, Transurethral Resection of Bladder Neck Obstructions. Dr. George Piness, Los Angeles, The Food Factor in Allergy. The following Colorado physicians, among others, will
Abstract 108: Pulselessness Despite Cardiopulmonary Resuscitation for Bradycardia in Hospitalized Children: Prevalence, Predictors of Survival, and Implications for Hospital Profiling
Authors: Rohan Khera, Yuanyuan Tang, Saket Girotra, Vinay M Nadkarni, Mark S Link, Tia Raymond, Anne-Marie Guerguerian, Robert Berg, Paul S Chan
Journal: Circulation (2018)

Background: Cardiopulmonary resuscitation (CPR) is initiated in hospitalized children with bradycardia and poor perfusion. However, it is unknown how often these children progress to pulseless in-hospital cardiac arrest (IHCA) despite CPR, and whether survival differs from primary pulseless IHCA. Methods: In Get With The Guidelines-Resuscitation (2000-2016), we identified all pediatric patients (age&gt;30 days, &lt;18 years) receiving CPR, and assessed the prevalence and predictors of survival among those progressing from bradycardia to pulselessness after initiation of CPR using multilevel Poisson regression that accounted for the pulseless rhythm. Results: Overall, 5592 pediatric patients were treated with CPR, of whom over half (2799) were for bradycardia with poor perfusion and the remaining 2793 were primary pulseless IHCAs. Among those with bradycardia, 869 (31%, or 16% of entire cohort) progressed to pulselessness after a median of 3 min of CPR (IQR 1- 9). Survival to discharge was 70% for bradycardia without pulselessness, 30% with bradycardia progressing to pulselessness, and 38% with primary pulseless IHCA (P&lt;.001). Children who became pulseless while receiving CPR for bradycardia had a 19% lower likelihood (RR 0.81 [0.70 - 0.93]) of surviving to hospital discharge than those initially pulseless. Among children who progressed to pulselessness while receiving CPR for bradycardia, longer time to pulselessness was an independent predictor of lower survival (ref: &lt;2 min, for 2-5 min: RR 0.54 [0.41 - 0.70]; for &gt;5 min: RR 0.41 [0.32 - 0.53], Figure ). Conclusions: Among non-neonatal pediatric patients in whom CPR is initiated, half have bradycardia with poor perfusion, and nearly one-third of these progress to IHCA despite CPR. Survival was lower for pediatric patients who subsequently became pulseless as compared to those who were initially pulseless. These findings have implications for care delivery and profiling hospital performance for pediatric IHCA.
Contamination of pharmaceutical products.
Journal: BMJ (1967)

PointersChest Injuries : Dr. WV. Bargh and colleagues emphasize the value of intermittent positivepressure ventilation in the management of severe crush injuries of the chest (p.131).Insulin Resistance: Dr. W. G. Oakley and col- leagues found that treatment with steroids was almost always successful in cases associated with P.C.A. antibodies and unsuccessful when the P.C.A. test is negative (p. 134).Premixed Gases: Dr
Council on Physical Therapy
Journal: JAMA (1942)

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
Longitudinal personalized urinary tumor DNA analysis in muscle-invasive bladder cancer from the neoadjuvant immunotherapy trial RJBLC-I2N003.
Authors: Ruiyun Zhang, Jingyu Zang, Feng Xie, Yue Zhang, Akezhouli Shahatiaili, Yiqiu Wang, Pan Du, Shidong Jia, Guanglei Zhuang, Yiran Huang, Haige Chen
Journal: Journal of Clinical Oncology (2022)

552 Background: RJBLC-I2N003 is an investigator-initiated study to evaluate the clinical activity and predictive biomarkers for neoadjuvant immunotherapy with toripalimab (anti-PD-1) in muscle invasive bladder cancer (MIBC). Methods: Twenty patients with pathologically confirmed MIBC were enrolled and received toripalimab (3 mg/kg Q2W, 4 cycles) before radical cystectomy. The safety and efficacy of neoadjuvant toripalimab were assessed. Serial urinary cell-free DNA (ucfDNA) and blood cell-free DNA (bcfDNA) were obtained at baseline and after each cycle of toripalimab treatment. Personalized minimal residual disease (MRD) assays and low-pass whole genome sequencing (LP-WGS) were applied to analyze liquid biopsy samples. Results: Eighteen patients (90%) completed all 4 cycles of neoadjuvant treatment. Grade 3-4 immune-related adverse events occurred in two patients (10%). Eight patients (40%) achieved a pathological complete response (pCR). Thirteen patients (65%) had no remaining invasive disease (pCR or pTisN0/pTaN0). Pre-treatment somatic variants and copy number abnormalities were prevalently detected in ucfDNA as compared to bcfDNA. On-treatment urinary tumor DNA (utDNA) clearance was associated with objective responses. Preliminary concordance was observed between molecular and pathological MRD status. Conclusions: These findings suggest that neoadjuvant administration of PD-1 blockade followed by surgical resection represents a feasible and efficacious approach to treat MIBC. The exploratory biomarker assessment demonstrates the potential utility of longitudinal personalized utDNA analysis to complement existing trial endpoints.
Evaluating the contribution of virtual peer-led support to comprehensive prostate cancer (PCa ) care: The AnCan experience.
Authors: Herbert M. Geller, John Ivory, Howard Wolinsky, James Schraidt, Rick Davis
Journal: Journal of Clinical Oncology (2022)

58 Background: Comprehensive care for PCa patients extends well beyond selecting therapies based on available guidelines. Patients should be supported to understand the disease, diagnostics, optimal treatment strategies, side-effects, avert morbidity and improve diet and exercise while combating stress. We present data supporting that patient participation in a video peer-led support group is integral to attaining these goals. Face-to-face peer groups are not readily accessible to many patients. AnCan has hosted virtual meeting support groups across the spectrum of malignancies and stages since 2010. We offer navigation, advocacy, and educational webinars. PCa is our cornerstone, including groups focusing on active surveillance/ high risk/recurrent/advanced disease, as well as under-60 patients. Methods: During spring 2021, a survey questionnaire focused on all disease stages was sent to 1174 men in the AnCan database; a second survey focused on active surveillance was send to 1200 active surveillance patients in the AnCan, Active Surveillance Patients International and Prostate Cancer International databases. We evaluated patient experience and how information acquired informed their treatment, interactions with their medical team, lifestyle, stress, and quality of life (QoL). Results: 238 responses were received for the AnCan survey, and 165 for the active aurveillance Survey, totaling. 389 independent responses. 228 (33%) were on Active Surveillance for low risk, and 93 (23%) had advanced PCa, largely distributed across North America. 154 (40%) repeatedly attend AnCan meetings. All (100%) indicated that meetings helped understand disease, navigate their treatment options, improve interaction with their medical teams and improve their quality of life (QoL). In the AnCan Suvey, 48 (19%) patients opted to move to different care teams and 32 (13 %) of those elected PCa specialists. 138 (58%) improved exercise, 90 (38%) improved diet, and 119 (50% ) reported stress reduction. 202 patients (85%) felt the groups to be welcoming, 102 (43%) connected with others, and 70 (30%) developed friendships. Of those who attend Active Surveillance meetings, 75 (68%) said that attendance helped them be their own best advocate, while 25 (23%) said that attendance informed them of new insights and treatments. Conclusions: The AnCan Support Group model increases patient knowledge, positively impacts treatment planning, and promotes lifestyle improvements while providing support to reduce stress, boosts confidence in navigating the disease, and improves QoL. AnCan empower patients to self-advocate and improve their disease experience. This is integral to optimize physician/patient interactions and improve outcomes. We advocate that virtual peer group attendance, based on our model, be included in NCCN treatment recommendations for PCa patients, especially with advanced disease.
Abstract 17230: Acute Flash Pulmonary Edema Leads to a Spot Diagnosis of Acute Mitral Regurgitation From Impella LP 5 Induced Chordae Rupture: A Success Story!!
Authors: Umama Gorsi, Kenneth Wong, Michail Vitellas
Journal: Circulation (2018)

Introduction: Impella devices are used as a temporary mechanical support for cardiogenic shock. Acute Mitral Regurgitation is a very rare complication after Impella placement. We present a case of sub-acute mitral regurgitation 2 days after removal of the Impala in a patient with cardiogenic shock after an acute anterior myocardial infarction. Case History: 37-year-old male with no significant past medical history was brought to the Emergency Room because of cardiac arrest at home. Patient had prolonged resuscitation time of about 45 minutes. After return of spontaneous circulation 12-lead electrocardiogram EKG showed typical anterior ST segment elevation MI. Right heart cath confirmed reflecting cardiogenic shock. Coronary angiogram revealed near ostial thrombotic occlusion of the LAD which was successfully treated with a drug-eluting stent. For severely reduced LV systolic function and severe cardiogenic shock Impella CP was inserted. Patient had an episode of cardiac arrest post procedure which was successfully resuscitated. On CCU day one we had a concern about positioning of Impella as it was considered to be under papillary muscle and under fluoroscopy and Echocardiogram guidance we attempted to reposition his Impella. Impella was removed on day 3. However all along we had difficulty adequately oxygenating him. His FiO2 was never below 50%. Eventually 2 days after Impella was removed (day 5 of admission) he had severe flash pulmonary edema. We could not oxygenate him on the ventilator on FiO2 of 100%. There was a concern of acute mitral regurgitation. This was confirmed by transthoracic and transesophageal echocardiogram showed flail anterior mitral leaflet P2 A3 likely chordae rupture. The patient was emergently taken to the operating room by cardiothoracic surgeon to undergo successful mitral valve replacement with a mechanical Saint Jude valve. From there patient slowly recovered. Patient was discharged home directly. Discussion: From the beginning it was felt that patient’s event is secondary to chordae rupture from the Impella device as the patient has otherwise demonstrated very good recovery post revascularization and therefore mechanical complication of MI would not be expected, also provided this was LAD territory along with the fact that the flail leaflet was not mediated by a papillary muscle rupture. Conclusion: It is pertinent to be very careful while repositioning Impella and one should always aim for a fluoroscopic guidance to reposition the device to avoid any damage to the surrounding structure.
Avelumab first-line (1L) maintenance + best supportive care (BSC) versus BSC alone in Asian patients with advanced urothelial carcinoma (UC): JAVELIN Bladder 100 subgroup analysis.
Authors: Masatoshi Eto, Jae-Lyun Lee, Se Hoon Park, Norihiko Tsuchiya, Po-Jung SU, T.W. Chan, Chirag Jyotiker Desai, Alessandra Di Pietro, Jing Wang, Robert J Laliberte, Seasea Gao, Howard Gurney
Journal: Journal of Clinical Oncology (2022)

486 Background: In the phase 3 JAVELIN Bladder 100 trial (NCT02603432), avelumab 1L maintenance therapy + BSC showed significantly longer overall survival (OS) vs BSC alone in patients with advanced UC that had not progressed with 1L platinum-based chemotherapy. We report efficacy and safety results in patients enrolled in Asia. Methods: Patients with unresectable locally advanced or metastatic UC without disease progression after 4-6 cycles of gemcitabine + cisplatin or carboplatin were randomized 1:1 to receive avelumab 1L maintenance + BSC or BSC alone, stratified by best response to 1L chemotherapy and visceral vs nonvisceral disease when initiating 1L chemotherapy. The primary endpoint was OS, assessed from randomization in all patients and patients with PD-L1+ tumors (Ventana SP263 assay). Results: 147 Asian patients were enrolled at sites in Japan, South Korea, Taiwan, Hong Kong, and India; 73 and 74 were randomized to receive avelumab + BSC or BSC alone, respectively. Median OS (95% CI) was 25.3 mo (18.6 mo-not estimable [NE]) with avelumab+ BSC vs 18.7 mo (12.8 mo-NE) with BSC alone (HR, 0.74 [95% CI, 0.434-1.260]) in all patients, and 26.1 mo (18.2 mo-NE) vs 19.4 mo (11.9 mo-NE), respectively (HR, 0.66 [95% CI, 0.279-1.541]), in the PD-L1+ subgroup (n = 71). With avelumab + BSC vs BSC alone, median (95% CI) progression-free survival was 5.6 (2.0-7.5) vs 1.9 (1.9-1.9) months (HR, 0.58 [95% CI, 0.383-0.864]) in all patients and 6.8 (1.9-11.2) vs 1.9 (1.9-3.8) months (HR, 0.63 [95% CI, 0.336-1.172]) in the PD-L1+ subgroup; objective response rates (95% CI) were 9.6% (3.9%-18.8%) vs 2.7% (0.3%-9.4%) and 12.5% (4.2%-26.8%) vs 3.2% (0.1%-16.7%), respectively. The most common treatment-emergent adverse events (TEAEs) of any grade (any causality) in the avelumab + BSC arm were pyrexia (23.6%), constipation, nasopharyngitis, and rash (19.4% each); grade ≥3 TEAEs were anemia (9.7%), amylase increased (5.6%), and urinary tract infection (4.2%). Conclusions: Efficacy and safety data support the use of avelumab 1L maintenance as the standard of care in Asian patients with advanced UC that has not progressed with 1L platinum-based chemotherapy. Clinical trial information: NCT02603432.