tbuckley/cabot-search huggingface dataset:
Statin type and survival of patients with metastatic castrate-resistant prostate cancer receiving abiraterone and enzalutamide: A nationwide retrospective cohort study.
Authors: Harrison Yoon, Suhong Luo, Kristen Marie Sanfilippo, Travis Linneman, Alison Whitmer, Martin W. Schoen
Journal: Journal of Clinical Oncology (2022)

50 Background: Studies have suggested that statin use is associated with prostate cancer mortality. However, uncertainties exist in how the solubility profile of statins impact cancer outcomes. Lipophilic statins have greater accessibility in extrahepatic tissues, which may lead to stronger inhibitory effects on cancer cells, whereas hydrophilic statins exhibit greater hepato-selectivity and therefore less likely to cause drug interactions and adverse events. Abiraterone (ABI) and enzalutamide (ENZ) are antiandrogen agents used in metastatic castrate-resistant prostate cancer (mCRPC). In this study, we sought to examine whether statin usage and lipophilicity of statins is associated with survival benefits in mCRPC patients receiving ABI or ENZ. Methods: We conducted a nationwide retrospective cohort study of the Veteran Affairs population. Patients with mCRPC who received statin therapy one year prior to initiation of either ABI or ENZ between 9/10/2014 and 6/3/2017 were included and followed until April 2020. Statins were categorized as lipophilic (atorvastatin, simvastatin, lovastatin, fluvastatin, cerivastatin, pitavastatin) and hydrophilic (rosuvastatin and pravastatin). A cox proportional hazards model was used to estimate adjusted hazards ratio (aHR) with 95% confidence interval (CI) of overall survival after controlling for known prognostic factors including age, Charlson-Romano Comorbidity Index, use of bone-modifying agents, Body-Mass Index, and prostate specific antigen levels. Results: A total of 4919 patients (mean age 75.0 years) were included in our cohort. Of those, 969 patients (19.7%) received lipophilic statins and 452 patients (9.2%) received hydrophilic statins. After adjusting for known factors, statin use was not associated with improved overall survival (aHR 0.93; 95% CI 0.87 – 1.00). Similarly, the use of lipophilic statins (aHR 0.98; 95% CI 0.90 – 1.06) or hydrophilic statins (aHR 0.90; 95% CI 0.80 – 1.01) were not associated with improved overall survival in mCRPC. Conclusions: Our study found no differences in overall survival between mCRPC patients with statin use compared to those without statins. When analyzing statin lipophilicity, we saw a higher trend towards survival in the hydrophilic statin group compared to the lipophilic statin group, which contradicts the direct anticancer benefits of lipophilic statins, but neither group reached statistical significance. Further studies analyzing statin usage and types with specific outcome measures such as cardiovascular events, duration of antiandrogen therapy, and adverse events related to ABI or ENZ will support in optimal therapy choices for mCRPC.
Re: Abiraterone Acetate and Prednisolone With or Without Enzalutamide for High-risk Non-metastatic Prostate Cancer: A Meta-analysis of Primary Results from Two Randomized Controlled Phase 3 Trials of the STAMPEDE Platform Protocol
Authors: Viktor Grünwald, Carsten-Henning Ohlmann, Boris Hadaschik
Journal: European Urology (2022)
Potentiation of humoral response to the BNT162b2 vaccine after the third dose in patients with solid cancer
Authors: V. Di Noia, F. Pimpinelli, D. Renna, M.T. Maccallini, L. Gariazzo, F. Riva, E. Sperandio, D. Giannarelli, F. Cognetti
Journal: Annals of Oncology (2022)
Rubella vaccination.
Authors: N Black
Journal: BMJ (1979)

<h3></h3> The efficacy of neurovascular thrombectomy depends on several fluid dynamic and material property considerations. Only an entirely impermeable clot that completely obstructs the tip of a thrombectomy device will be governed in its removal by force (of suction) divided by area (of the catheter lumen). However, nearly all blood clots are both porous and deformable. Clot porosity enables continuous fluid flow, which results in drag forces on the solid elements of the network<sup>1</sup> that promote ingestion. Clot permeability is closely related to clot perviousness, which is a measure of contrast agent accumulation within clots, detectable by computed tomography angiography.<sup>2</sup> Moreover, clot perviousness is associated with first pass success with thrombectomy.<sup>3</sup> Clot deformation also promotes clot ingestion into a narrow bore catheter. Benchtop data has demonstrated that clots can elongate from 20% to 100% prior to breakage.<sup>4 5</sup> Therefore, greater fluid flow during thrombectomy promotes greater clot ingestion through multiple mechanisms. Greater fluid flow can also promote more rapid clot ingestion during thrombectomy since the higher velocities convect clots faster during ingestion. Decreases in thrombectomy procedure time will reduce risk and post-procedure complications. New benchtop experimental and pre-clinical data will be presented that support the relevance of these mechanical mechanisms of effective blood clot removal in neurovascular applications. <h3>References</h3> Stanford, Sabra, <i>et al</i>. <i>BMC Neurol</i> 2015;<b>15</b>:35. Benson, Fitzgerald, <i>et al</i>. <i>Journal of NeuroInterventional Surgery</i> 2020;<b>12</b>(1):38–42. Mokin, Waqas, <i>et al</i>. <i>J Neurointerv Surg</i>, 2020. Tutwiler, Singh, <i>et al</i>., <i>Sci Adv</i> 2020;<b>6</b>(35): eabc0496. Krasokha, Theisen, <i>et al</i>. Mat.-wiss. u.<i>Werkstofftech</i> 2010;<b>41</b>(12):1019–1024. <h3>Disclosures</h3> <b>N. Chesler:</b> 1; C; MIVI Neuroscience. 2; C; Inari Medical, MIVI Neuroscience.
Efficacy and safety of lenvatinib (LEN) plus pembrolizumab (PEMBRO) versus sunitinib (SUN) in the East Asian subset of patients with advanced renal cell carcinoma (aRCC) from the phase 3 CLEAR trial.
Authors: Sun Young Rha, Toni K. Choueiri, Vsevolod B. Matveev, Anna Alyasova, Sung-Hoo Hong, Teresa Alonso Gordoa, Howard Gurney, Georg A. Bjarnason, Tomas Buchler, Paolo Pedrazzoli, Toshio Takagi, Se Hoon Park, Jae-Lyun Lee, Rodolfo F. Perini, Cixin He, Jodi A. McKenzie, Masatoshi Eto
Journal: Journal of Clinical Oncology (2022)

338 Background: In the phase 3 CLEAR trial that included patients with aRCC, LEN + PEMBRO demonstrated significant improvements in progression-free survival (PFS; hazard ratio [HR] 0.39; 95% CI 0.32, 0.49; P &lt; 0.001), overall survival (OS; HR 0.66; 95% CI 0.49, 0.88; P = 0.005) and objective response rate (ORR; odds ratio 4.35; 95% CI 3.16, 5.97) vs SUN. Here we report the efficacy and safety results of the East Asian population subset of the CLEAR trial. Methods: Patients with aRCC and no prior systemic therapy were randomized (1:1:1) to receive 1 of 3 treatments including LEN 20 mg PO QD + PEMBRO 200 mg IV Q3W and SUN 50 mg PO QD (4 weeks on/2 weeks off). Randomization was stratified by geographic region and MSKCC prognostic groups. This analysis compares the efficacy and safety of LEN + PEMBRO vs SUN in the East Asian subset of the CLEAR trial including patients from Japan and the Republic of Korea. The primary endpoint was PFS; secondary endpoints included OS, ORR and safety. An independent review committee assessed tumors per RECIST v1.1. Median PFS and OS were calculated using the Kaplan-Meier method; HR and 95% CI were estimated by a stratified Cox model. Odds ratios were estimated by a stratified Cochran-Mantel-Haenszel test. Results: Of the 1069 patients randomized, 75 patients in the LEN + PEMBRO group and 65 patients in the SUN group were from East Asia. PFS was improved with LEN + PEMBRO vs SUN (median 22.1 vs 11.1 mo; HR 0.38, 95% CI 0.23, 0.62). Median OS was not reached for both arms; the HR for OS comparing LEN + PEMBRO vs SUN was 0.71, 95% CI 0.30, 1.71. ORR was improved with LEN + PEMBRO vs SUN (65.3% vs 49.2%; odds ratio 2.14, 95% CI 1.07, 4.28). Grade ≥3 treatment emergent adverse events (TEAEs) occurred in 88.0% of patients in the LEN + PEMBRO group and in 79.7% of patients in the SUN group. The incidences and types of TEAEs were generally similar to the overall CLEAR population and were manageable with dose adjustments and appropriate concomitant therapies. Conclusions: Efficacy results for patients in the East Asian subset of the CLEAR trial were consistent with the results of the overall population. The safety profile of LEN + PEMBRO in the East Asian subset was also generally consistent with that of the overall population. Clinical trial information: NCT02811861. [Table: see text]
Another "first" exposed
Authors: S. Vaisrub
Journal: JAMA (1978)

Having cast many stones at those who report "first," allegedly previously unreported observations, I now find myself living in a glass house. "A Dithyramb to the Dictionary" (239:2159, 1978) contains a transgression to which N. G. Demy of East Hampton, NY, calls attention in an eloquent letter. The letter reads: I beg to differ with your editorial that "No muse of the dictionary resided on Parnassus" and that "No poet dedicated an ode to a dictionary" or that "No chorus chanted paeans to a lexicographer." Franklin Pierce Adams did all that, and since you are unlikely to find him on the shelves of a library today, I give you his paeans of praise in "A Lexicographer's Love-Poem" in "Lines on Reading Frank J. Wilstach's 'A Dictionary of Similes' " (which should delight those interested in metaphors), and "To a Thesaurus." As for me, I'm with Alice who protested "What good is
Clinical and molecular features of low prostate-specific membrane antigen (PSMA) expression in patients (pts) with metastatic castration resistant prostate cancer (mCRPC).
Authors: Ivan de Kouchkovsky, Li Zhang, Jiaoti Huang, Kai Trepka, Jonathan Chou, Adam Foye, David Shui, Chris Wong, Verena Friedl, Alana Weinstein, Thomas A Hope, David A. Quigley, Josh Stuart, Tomasz M. Beer, Robert Evan Reiter, Martin E. Gleave, Christopher P Evans, Felix Y Feng, Eric Jay Small, Rahul Raj Aggarwal
Journal: Journal of Clinical Oncology (2022)

167 Background: Low PSMA uptake on positron-emission tomography is seen in up to 30% of mCRPC pts and represents a clinically distinct subgroup with adverse outcomes. We assessed transcriptional and clinical features associated with low PSMA ( FOLH1) gene expression in mCRPC. Methods: A retrospective analysis of mCRPC biopsy samples with RNA-seq data was undertaken. Normalized FOLH1 expression was compared across histologic subtypes and sites of disease. We assessed the association between FOLH1 expression, selected androgen receptor (AR) target genes, master regulators of neuroendocrine differentiation, and previously validated AR activity and treatment-associated small cell neuroendocrine carcinoma (t-SCNC) transcriptional signature scores using Pearson correlations. Associations between FOLH1 and both PSA 50 response to subsequent AR-targeted therapy and overall survival (OS) were examined by logistic regression and Cox proportional hazard models, respectively. Results: Samples from 97 pts were identified, of which 18% harbored t-SCNC histology. 45% of pts had visceral metastases at the time of biopsy, and 41% received subsequent AR-targeted therapy. Median FOLH1 expression was lower in pts with visceral metastases vs no visceral metastases (14.7 vs 15.6, p = 0.02) but was not significantly different across t-SCNC vs adenocarcinoma biopsies (14.3 vs 15.4, p = 0.13). FOLH1 expression was positively correlated with AR transcriptional activity and AR target genes, and negatively correlated with master regulators of neuroendocrine differentiation and t-SCNC transcriptional signature scores (Table). Low FOLH1 expression did not predict PSA 50 response to subsequent AR-targeted therapy (OR 0.97, p = 0.8), but was associated with shorter OS on univariate analysis (HR 1.09, 95% CI 1.02-1.16, p=0.01). A post-hoc analysis revealed a trend towards decreased median OS in pts with FOLH1 expression &lt;12 (7.5 vs 17.1 months, log-rank p = 0.06). Conclusions: In this retrospective analysis of mCRPC pts, low FOLH1 expression was associated with transcriptional features of t-SCNC, decreased AR activity, and shorter OS. These findings are hypothesis-generating and prospective validation is needed.[Table: see text]
Real-world treatment outcomes of first-line axitinib plus pembrolizumab in patients with advanced renal cell carcinoma in the United States.
Authors: Yousef Zakharia, Despina Thomaidou, Benjamin Li, Gordan Siu, Rebecca Levin, Anna Vlahiotis, Giovanni Zanotti
Journal: Journal of Clinical Oncology (2022)

314 Background: The combination of axitinib plus pembrolizumab (AXI+PEM) is a standard of care in the first-line (1L) treatment of patients with advanced clear cell renal cell carcinoma (RCC). This analysis describes the demographic and clinical characteristics, treatment and outcomes of patients receiving 1L AXI+PEM in a real-world setting. Methods: Medical record data were extracted from the Flatiron Health Database, which includes ̃280 cancer clinics across 800 sites in the US. Patients had confirmed Stage IV or metastatic RCC and initiated 1L AXI+PEM on or after 1/1/2018 to 3/31/2021. Tumor response is reported as best overall response to 1L therapy; real-world progression-free survival (rwPFS) and overall survival (rwOS) are reported as patients without a clinical event (rwPFS; progression/death; rwOS; death) at landmark time periods (3, 6, 9, and 12 months); denominators include censored patients. Other data are reported as medians (min, max) unless otherwise noted. Results: Three hundred and fifty-five patients received 1L AXI+PEM, with follow-up of 9.7 (0.1–24.3) months. Most patients were male (69.6%), and age was 68.0 (21.0–84.0) years. At diagnosis, 55.5% of patients had Stage IV RCC and 77.2% of patients had clear cell histology. IMDC Risk Score was favorable, intermediate, and poor in 27 (7.6%), 126 (35.5%), and 76 (24.4%) patients, respectively. At the time of analysis, 270 patients (76.1%) received only 1L therapy with AXI+PEM, while 85 patients (24.3%) received ≥1 subsequent line of treatment. VEGF-R inhibitors were the most commonly used second-line (2L) treatment (51 patients, 60.0%), with cabozantinib as the most frequently used VEGF-R inhibitor (40 patients, 47.1%). rwPFS at 3 months and 1 year was achieved by 248 patients (69.9%) and 77 patients (21.7%), respectively. rwOS ranged from 293 patients (82.5%) surviving at 3 months to 142 patients (40.0%) surviving at 1 year. Best overall response rate to 1L was 47.9% (complete or partial response observed in 170/355 patients). Conclusions: This study provides real-world evidence for the use and effectiveness of 1L AXI+PEM in patients with advanced RCC. AXI+PEM was used across all IMDC risk groups. While these initial finding support the use of AXI+PEM, additional follow-up is warranted to provide further understanding of the clinical outcomes and treatment patterns of patients with advanced RCC in the US receiving 1L AXI+PEM.
Experimental models of acute kidney injury for translational research
Authors: Neil A. Hukriede, Danielle E. Soranno, Veronika Sander, Tayla Perreau, Michelle C. Starr, Peter S. T. Yuen, Leah J. Siskind, Michael P. Hutchens, Alan J. Davidson, David M. Burmeister, Sarah Faubel, Mark P. de Caestecker
Journal: Nature Reviews Nephrology (2022)
New Conception of Angina Pectoris
Authors: R. Wyburn-Mason
Journal: BMJ (1948)

labour delivered by caesarean section in the Birmingham Maternity Hospital; positive cultures were obtained twice (anaerobic streptococci, and B. coli), and both infants made normal progress.It would therefore seem possible that infection of the foetus during prolonged labour is far more common than is generally imagined, and this might well account for the increase in rate of the foetal heart so commonly observed in these circumstances.It would also appear that neonatal immunity or resistance to infection is remarkably high.-Iam, etc., Birmingham.
Retinal detachment.
Authors: A H Chignell
Journal: BMJ (1987)

positive controls.Mossman and Blau (p 680) studied Tinel's sign in a smaller group of patients and showed that the sensitivity of the test was increased by extending the wrist, to tense the contents of the carpal tunnel, and by percussing with a broad based "Queen Square" tendon hammer.The proportion of false positive results was not increased.Treatments for carpal tunnel syndrome include rest, night splints, diuretics, steroid injection into the carpal tunnel, and wide surgical division of the flexor retinaculum.Many hospital studies report a poor or only temporary response to non-surgical treatment, but uncontrolled experience from general practice suggests some benefit from rest and diuretics' and considerable benefit from one or two injections of hydrocortisone for patients who have only acroparaesthesia.Perhaps some patients with milder symptoms' have self limiting swelling of the synovium and flexor tendon sheaths and reach hospital less often.An operation is essential, however, if the patient has muscular weakness or wasting.Dysaesthesia is common after operation, and sensory recovery may take up to 12 months; in contrast, there may be little or no motor recovery.Gellman's study is a stimulus and a challenge.The doctor must progressively refine his differential diagnosis, and to do this he needs to choose those tests that most quickly and certainly discriminate between one condition and another.General practice teachers have emphasised the need to know the specificity as well as the sensitivity of factors that constitute a diagnosis.5Yet, although there are some data on the prevalence of symptoms in healthy people,67 the specificity of the various parts of the clinical examination and tests used by doctors are largely unknown.This study is a small but useful step in the right direction.
Real-world assessment of changing treatment patterns and sequence for patients with metastatic renal cell carcinoma (mRCC) in the first-line (1L) setting.
Authors: Neil J. Shah, Sneha Sura, Reshma Shinde, Junxin Shi, Rodolfo F. Perini, Singhal Puneet, Nicholas J. Robert, Nicholas J. Vogelzang, Robert J. Motzer
Journal: Journal of Clinical Oncology (2022)

302 Background: Several immune-oncology (IO) agents and/or tyrosine kinase inhibitors (TKIs) have received approval for treatment of mRCC in 1L setting by Food and Drug Administration (FDA) over last few years. Limited data exists on evolving real-world treatment patterns and sequence in mRCC patients receiving these agents, especially at the community oncology setting. Methods: We used data from The US Oncology Network of over 1,300 providers from over 480 sites across United States from 01/01/2018 to 12/31/2020 (study period). Eligible study population included mRCC patients who received ipilimumab + nivolumab (Ipi+nivo) (IO+IO); pembrolizumab + axitinib (Pembro+axi) (IO+TKI); and axitinib (Axi) or cabozantinib (Cabo) or pazopanib (Pazo) or sunitinib (Suni) (TKIs monotherapy) in 1L setting until 09/30/2020. Descriptive statistics were used for cohort characterization. Results: We identified 3,756 mRCC patients, of which 1,538 were eligible including 42% (n=641) IO+IO, 18% (n=279) IO+TKI, and 40% (n=618) TKI monotherapy. The median age for the entire cohort was 67.1 years (range 25.0, 93.3), 70% (n=1,076) were male, 70% (n=1,081) were white, 38% (n=587) had BMI ≥ 30 and 79% (n=1,208) had clear cell histology. Among entire cohort, 87% (n=1,338) had intermediate/poor risk score as per International mRCC Database Consortium risk model. We noted a trend towards increased utilization of IO+IO and IO+TKI following their respective FDA approvals (IO+IO: April 2018, IO+TKI: April 2019) (Table). During the study period, overall, 35% (n=535), 12% (n=184), and 4% (n=62) mRCC patients received second-line (2L), third-line (3L) and fourth-line (4L) treatments, respectively. Cabo (49%) and pazo (12%); cabo (51%) and ipi+nivo (23%); and nivo (45%) and ipi+nivo (20%) were the most common 2L treatments in IO+IO, IO+TKI, and TKI monotherapy cohorts, respectively. Conclusions: This large real-world study examined use of new FDA approved mRCC treatments and their impact on treatment paradigm. The results show a rapid adaptation of these newer treatments in the community oncology settings. A longer follow-up is needed to assess their clinical impact and optimal treatment strategy in subsequent setting.[Table: see text]
Flatulence.
Authors: N B Eastwood
Journal: BMJ (1971)

largeness in body, nor no sickness, nor lack of natural functions in those things that properly belong to the procreation of child- ren, but contrarywise, by judgement of physicians that know her estate on those things and by the opinion of women, being most acquainted with her Majesty's body in such things as properly appertain, to show probability of her aptness to have children, even at this day."3If the evidence of this memorandum is accepted, the factors which influenced Elizabeth against marriage were probably political, psychological, and religious, not to mention personal survival, rather than any physical complaint.
The Diagnosis of Gastric Cancer.
Journal: JAMA (1884)

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Bronchography
Authors: E. J. G. Glass
Journal: BMJ (1939)

SumimaryAntigonadotrophic activity was demonstrable in the serum of nine patients with undescended testes who were injected intramuscularly, either daily or twice weekly, for twelve weeks with an extract of the serum of pregnant mares.The antigonadotrophic activity (a) developed after four to six weeks' treatment, and subsequently in most cases rose rapidly; (b) was not proportional to the amount of extract which was injected ; (c) usually decreased at the end of treatment, but was still present for three months or more-in two patients, however, activity increased for about three weeks after injections were dis- continued ; (d) was greater in patients who received twice-weekly injections of extract.The previous observation of Rowlands (1938) on the specificity of a similar antiserum, raised in rabbits, was confirmed.The human antiserum did not inhibit, in immature rats, the action of extracts of either human pituitary gland or urine of pregnancy.No improvement in the position of the testes of the patients was observed during treatment with this extract, but in three of six patients subsequently treated with extract of urine of pregnancy descent of the testes was successfully obtained.We desire to thank Dr. A. N. Macbeth of N.V. Organon for supplies of the extract of pregnant mares' serum and extract of human urine of pregnancy ("pregnyl ").