tbuckley/cabot-search huggingface dataset:
Sequential intravesical valrubicin and docetaxel for the treatment of nonmuscle invasive bladder cancer.
Authors: Ian Mitchell McElree, Vignesh T. Packiam, Ryan L. Steinberg, Sarah L. Mott, Paul T. Gellhaus, Kenneth G. Nepple, Michael A. O'Donnell
Journal: Journal of Clinical Oncology (2022)

496 Background: Intravesical gemcitabine-docetaxel (Gem/Doce) has emerged as an efficacious and well-tolerated therapy for NMIBC. At first cytoscopic evaluation, success rate for BCG failures is 75-80% with 60% of responders remaining disease free at 24 months. Success rates are even higher for BCG naïve patients with close to 90% disease free at 3 months, and 93% of responders HG disease free at 24 months. There is an unmet need for effective bladder-sparing regimens for Gem/Doce failures. FDA-approved agents in this setting have poor long-term efficacy; Valrubicin has an 8% 24-month disease free rate, and recently approved Pembrolizumab has less than 20% complete response at 1 year. Based on poor efficacy of alternatives, we evaluated sequential intravesical valrubicin-docetaxel (Val/Doce) as a rescue therapy for NMIBC. Methods: We retrospectively identified all patients with NMIBC who were treated with Val/Doce between April 2013 and June 2021. Patients were included with intent to receive 6 weekly intravesical instillations of sequential 800 mg valrubicin and 37.5 mg docetaxel after complete TURBT. Monthly maintenance of 2 years was initiated if disease free at 3-month cytoscopic evaluation. The primary outcome was recurrence-free survival (RFS). Progression events included the development of muscle invasive or metastatic disease as well as any cystectomy. Survival was assessed using the Kaplan-Meier method and log rank test, indexed from start of Val/Doce induction. Surveillance was performed according to AUA guidelines. Results: The final cohort included 75 patients with median follow-up of 21 months. Of these patients, 12 were treated with Val/Doce for low-grade Ta disease, with 60% disease free at 2 years and no subsequent HG occurrences. The remaining 63 patients had high-grade disease of which 86% were BCG failures and 89% were Gem/Doce unresponsive. The 2 year RFS for high-grade patients was 39%. CIS was present in 56% of the cohort. RFS was similar for those with and without CIS. Progression occurred in 12 of the patients with high-grade disease. Of note, 10 underwent cystectomy and 2 died of metastatic bladder cancer, yielding a bladder cancer specific death rate of 3%. Overall and cystectomy-free survival was 88 and 85% at 24 months, respectively. The most commonly reported side effects were bladder spasms (24%), urinary frequency (13%), and dysuria (11%). There were 3 patients who could not tolerant a full induction course. Conclusions: Sequential intravesical valrubicin-docetaxel will rescue a substantial portion of patients with HG NMIBC failing Gem/Doce or BCG. Thus, the regimen allows a high proportion of patients ( &gt; 80%) to retain their bladders with an acceptable ( &lt; 20%) progression rate without succumbing to bladder cancer-related death ( &lt; 5%).[Table: see text]
Associations of history of vaccination and hospitalization due to infection with risk of monoclonal B-cell lymphocytosis
Authors: Nicholas J. Boddicker, Sara J. Achenbach, Sameer A. Parikh, Geffen Kleinstern, Esteban Braggio, Aaron D. Norman, Kari G. Rabe, Celine M. Vachon, Connie E. Lesnick, Timothy G. Call, Janet E. Olson, James R. Cerhan, Neil E. Kay, Curtis A. Hanson, Tait D. Shanafelt, Susan L. Slager
Journal: Leukemia (2022)
A prospective study of the relationship between CRPC patient’s quality of life after enzalutamide and serum testosterone levels measured via LC-MS/MS.
Authors: Yoshiyuki Miyazawa, Toshiyuki Nakamura, Yutaka Takezawa, Nobuaki Shimizu, Yasushige Matsuo, Haruyuki Ogura, Tomoyuki Takei, Seiji Arai, Yoshitaka Sekine, Kazuhiro Suzuki
Journal: Journal of Clinical Oncology (2022)

79 Background: Enzalutamide (ENZ) is used to treat patients with castration-resistant prostate cancer (CRPC). Quality of life (QOL) during ENZ treatment for CRPC patients is very important, but the markers that predict QOL are unknown. We investigated the relationship between serum testosterone (T) levels before ENZ and QOL changes in CRPC patients. Methods: We conducted a prospective study from 2014 to 2018 at Gunma University Hospital and related facilities. We analyzed 95 patients who were able to evaluate QOL by FACT-P before, 4 weeks, and 12 weeks after ENZ administration. We measured serum T levels using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This study was approved by the institutional review board of Gunma University Hospital (No.1177). Results: The study population of 95 patients had a median age of 72 years and median PSA of 21.6 ng/ml. The median overall survival from the time of ENZ administration in 95 cases was 26.8 months. The median serum T levels before ENZ treatment was 50.0 pg/ml. The mean total FACT-P score before ENZ administration, 4 weeks and 12 weeks later were 95.8, 91.7, and 90.1, respectively. 95 patients were divided into two groups, a high T levels (T-High) group and a low T (Low-T) group, and changes in FACT-P were examined. The mean FCAT-P values in the High-T and Low-T groups were 98.5 and 84.6 after 4 weeks and 96.4 and 82.2 after 12 weeks, which were significantly higher in the High-T group (p &lt; 0.05, respectively). In the Low-T group, the mean FACT-P value after 12 weeks was significantly lower than that before administration (p &lt; 0.05). Conclusions: It was suggested that the serum T levels of CRPC patients before ENZ treatment may be useful for predicting marker of QOL changes after ENZ treatment.
Tumor genomic landscape in smokers compared to non-smoker patients with locally advanced or metastatic urothelial carcinoma.
Authors: Nishita Tripathi, Nicolas Sayegh, Yeonjung Jo, Haoran Li, Roberto Nussenzveig, Benjamin Haaland, Vinay Mathew Thomas, Sumati Gupta, Deepika Sirohi, Umang Swami, Neeraj Agarwal, Benjamin L. Maughan
Journal: Journal of Clinical Oncology (2022)

554 Background: Cigarette smoking is a known risk factor for bladder cancer. Smokers have been reported to have greater ERCC2-Signature mutations and APOBEC-Signature 13 mutations when compared to non-smokers in a TCGA based study (PMID: 33849962). Our objective was to assess the frequency of targetable genomic alterations in smokers (current or past) vs never smokers patients (pts) with locally advanced or metastatic urothelial carcinoma (mUC). Methods: In this IRB approved retrospective study, smokers vs non-smokers pts with mUC undergoing tumor comprehensive genomic profiling (CGP) from CLIA-certified laboratory were included. Genes with alterations (GA) in &lt; 5% pts and variants of unknown significance were excluded from the analysis. A chi square test was used to compare gene frequency aberration and the analysis was adjusted for false discovery using Benjamini-Hochberg (BH) correction. The median number of genomic aberrations per pt was compared using Wilcoxon rank-sum test. Results: 137 pts were eligible and included. Smokers (n=70) and non-smokers (n=67): median age, 67 vs 68 years; male vs female: 55/15 vs 42/25. The genomic aberrations enriched in smokers and non-smokers are shown in the table. The most common GA observed in smokers were TERT, TP53, CDKN2B, RB1 and KDM6A; and non-smokers were TERT, TP53, CDKN2B, PIK3CA and RB1 (Table). Tumor mutation burden and the frequency of genomic aberrations per pt were similar in both groups. Conclusions: Herein, we independently validate the findings by Walasek, Almassi et. al. (abstract B20, AACR 2020) of no significant difference in the tumor GA between smokers vs non-smokers pts with advanced urothelial carcinoma, despite high prevalence of targetable genomic aberrations in both cohorts. Future directions should include the investigation of epigenomic changes and transcriptomic profiling to further elucidate the effect of smoking on bladder cancer.[Table: see text]
Hearing voices.
Authors: J Cutting
Journal: BMJ (1989)

edited video tapes, and a group already exists-the British Cardiovascular Intervention Society-that could organise regular postgraduate programmes along these lines.As in the United States, such meetings will provide an essential forum for teaching and discussing new developments -such as lasers, stents, and atherectomy catheters -and are probably the cornerstone for training new and established practitioners alike.The number of angioplasties in Britain has doubled yearly from 712 in 1984 to 4200 in 1987.A further increase to around 5500 occurred in 1988.Faced with this growth, consultant cardiologists will in future probably wish to practise angio- plasty.Current and aspiring senior registrars should thus seriously consider fulfilling the American guidelines for acquiring this skill.On completion of the implementation of the recommended training programme most cardiologists will be competent to perform simple or single vessel coronary angioplasty procedures.More complex or multivessel lesions may be best tackled by subspecialists.7But the message is clear: an expanded well trained workforce is needed to tackle this growing workload.
Differential dendritic integration of long-range inputs in association cortex via subcellular changes in synaptic AMPA-to-NMDA receptor ratio
Authors: Mathieu Lafourcade, Marie-Sophie H. van der Goes, Dimitra Vardalaki, Norma J. Brown, Jakob Voigts, Dae Hee Yun, Minyoung E. Kim, Taeyun Ku, Mark T. Harnett
Journal: Neuron (2022)
Respiratory Effects of Ethyl Alcohol Intoxication
Authors: Richard L. Witt
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Death from acute alcohol intoxication is thought by many to be due to respiratory failure. Yet in recent laboratory studies, moderately intoxicating doses of ethyl alcohol (120 mg/100 ml) had no consistent effect on respiratory rate or minute volume and sometimes increased ventilation. We therefore studied ten severely intoxicated adults brought to the Cincinnati General Hospital emergency unit. Very high blood concentrations of ethyl alcohol (BEC) in these patients caused only moderate respiratory depression. The patients were chronic alcoholics without clinical evidence of cardiopulmonary disease. Screening of blood samples by means of gas chromatography excluded the presence of other drugs in addition to ethyl alcohol. Of the ten patients, two were unconscious and eight were conscious but lethargic, with slurred speech and incoordination. Arterial blood for pH and gas analysis was drawn while the patients breathed room air. Venous BEC were determined by gas chromatography. Arterial blood
Sex Differences in Peripheral Artery Disease
Authors: Maria Pabon, Susan Cheng, S. Elissa Altin, Sanjum S. Sethi, Michael D. Nelson, Kerrie L. Moreau, Naomi Hamburg, Connie N. Hess
Journal: Circulation Research (2022)

Peripheral artery disease (PAD) is a prevalent condition that confers substantial morbidity and mortality and remains underdiagnosed as well as undertreated in the overall population. Although PAD prevalence is similar or higher in women compared with men, associations of traditional and nontraditional risk factors with PAD and clinical manifestations of PAD differ by sex and may contribute to delayed or lack of diagnosis in women. Such sex-based differences in the manifestation of PAD may arise from sexual dimorphism in the vascular substrate in health as well as sex variation in the responses to vascular stressors. Despite the availability of proven therapies for improving symptoms and reducing risk of ischemic cardiovascular and limb events among patients with diagnosed PAD, important sex differences in treatment and outcomes have been observed. We provide an overview of current knowledge regarding sex differences in the epidemiology, pathophysiology, clinical presentation, and management of PAD.
Cor de ballet
Authors: S. Vaisrub
Journal: JAMA (1980)

Lest, carried away by our imagination, we read into the title "The Heart of a Dancer"<sup>1</sup>allusions to a great love affair in the life of a celebrated prima ballerina or a renowned male ballet star, the subtitle promptly reminds us that what it is all about is not romance but "the noninvasive cardiac evaluation of professional ballet dancers." This reminder may come as a bit of a jolt. We are accustomed to viewing dancers as artists in need of appreciation rather than as athletes in need of cardiac evaluation. To assess the effect of ballet training on the heart, Cohen and associates<sup>1</sup>compared some basic cardiovascular variables in 30 (15 women and 15 men) American Ballet Theatre dancers with those in 15 matched sedentary control subjects. On the basis of physical examination findings, echocardiography, phonocardiography, and ECGs, they established statistically significant differences. Male dancers, for instance, had
Abstract 134: Patients’ Perspectives on Enrollment in Research Using the Exception From Informed Consent: An Integrated Survey
Authors: Neal W Dickert, Michelle H Biros, Deneil K Harney, Elizabeth B Jones, Andrea R Mitchell, Victoria M Scicluna, Robert Silbergleit, Candace D Speight, David W Wright, Rebecca D Pentz
Journal: Circulation (2018)

Introduction: Relatively minimal data exist regarding perspectives of patients (or surrogate decision-makers) after enrollment in clinical trials using the exception from informed consent (EFIC) for emergency research, a regulation essential for resuscitation research. Prior studies have shown that attitudes are generally positive but have enrolled a small proportion of participants and may have been subject to selection bias. Methods: As part of the study protocol, a 10-item paper-and-pencil survey was integrated into the protocol for all sites of the Established Status Epilepticus Treatment Trial (ESETT) trial, a randomized trial of three treatments for benzodiazepine-refractory status epilepticus in pediatric and adult patients. All patients (or surrogate) were given the survey after being asked for consent to continue in ESETT. Primary domains included acceptance of trial enrollment, acceptance of EFIC, and views on which population to include in community consultation. Response items primarily used a 5-point Likert scale. Simple descriptive statistics were tabulated. Results: In total, 317 of 443 patients/surrogates completed the survey (71.6% response). Only 7.3% (23/317) disagreed with the statement “I am glad that my family member/I was included in the ESETT research study,” and 24.9% (79/317) disagreed with being included under EFIC. When asked whom researchers should consult during community consultation, 81.1% (257/317) said patients who have had seizures, 64.7% (205/317) said their family members, and individuals at particular risk for seizures (50.8%) (161/317) were most frequently chosen. Only 26.5% (84/317) felt that members of the general public should be consulted. Conclusions: This is the largest study to date of participants’ perspectives on being enrolled in an EFIC trial. Rates of enrollment acceptance were relatively high; acceptance of EFIC specifically was slightly lower. There is much greater support for consulting individuals with connections to the disease under study than the general public or other groups. These findings further suggest that targeted community consultation may be appropriate and the importance of clear communication with participants after enrollment regarding reasons for EFIC use.
399O Oxaliplatin plus fluoropyrimidines as adjuvant therapy for colon cancer in elderly patients: A subgroup analysis from TOSCA trial
Authors: G. Rosati, F. Galli, S. Lonardi, K.F. Dotti, M. Ronzoni, M.G. Zampino, M. Banzi, V. Pusceddu, F. Pasini, S. Bozzarelli, N. Pella, C. Codecà, V. Montesarchio, A. Mambrini, A. De Stefano, L. Ciuffreda, S.E. Rebuzzi, F. Galli, D. Bilancia, R. Labianca
Journal: Annals of Oncology (2020)
Aspartyl (Asparaginyl) <b><i>β</i></b>-hydroxylase (AABH) as a serum biomarker for prostate cancer, to identify prostate cancer, regardless of PSA level.
Authors: Mahmood Moshiri, Arsha Moshiri, Hamed Pashaei, Kiarash Moshiri, Reza Nazari, Hassan Monhemi
Journal: Journal of Clinical Oncology (2022)

226 Background: Prostate Cancer (PC) is the most common form of cancer in men in the United States. In their lifetime, approximately 1 out of every 6 American men will develop PC. The chances of developing PC increase dramatically after age 50 with more than 72% of cases occurring in individuals over 65 years of age. Methods: We have investigated the use of aspartyl (asparaginyl) β-hydroxylase (AABH) as a cancer biomarker. We have developed a sandwich ELISA for its detection. Here this assay was utilized to screen sera from patients with prostate cancer and PSA values in various ranges. Results: AABH levels were assessed in sera from 263 individuals with PC and 73 men over 50 years of age not known to have cancer. The levels of AABH in the two groups were &gt; 3.00 ng/ml and &lt; 3.00 ng/ml, respectively. The overall sensitivity and specificity of the test were 97.5% and 96%. AABH and PSA levels were also compared. The AABH values and sensitivities in individuals with PC and PSA values in the ranges &lt; 2 ng/ml, 2-4 ng/ml and &gt; 4 ng/ml were &gt; 3.00 ng/ml, 99% (n = 115); &gt; 3.00 ng/ml, 98% (n = 64) and &gt; 3.00 ng/ml, 95% (n = 114). Conclusions: The present study of AABH indicates that cancer group can be clearly distinguished from normal healthy controls. Moreover, the study indicates that AABH might be used to identify disease in individuals with questionable PSA values. These results support to the establishment of routine screening of serum AABH as a means to detect those who need referral for prostate biopsy. The use of AABH testing may enhance current prostate cancer screening practices by both identifying individuals with low but suspicious PSA values who should be recommended for biopsy and reducing the number of false biopsies indicated by positive PSA tests. Serum AABH levels are significantly elevated in individuals with prostate cancer. Using a cutoff value of 3ng/ml, overall sensitivity of the assay for prostate cancer is 97%. The test has a specificity of 96% in healthy men over 50 years of age. AABH is elevated in prostate cancer tissue but NOT in normal prostate or in Benign Prostatic Hyperplasia (BPH). Serum AABH levels are NOT correlate with PSA levels.
Clinical Lectures
Authors: C. F. Favell
Journal: BMJ (1845)

I select from the numerous patients at present in the wards, the case of Samuel Binghain, as the stubject of a few observations this evening.I will first relate to you as briefly as I can, the details of the case, and then add some explanatory remarks.Samuel Binghamii, aged 26, a sitigle man, of spare labit, and by trade a whitesuiiith, was admitted into
Preventive effect of levodopa on vitiligo development: a nationwide case–control study
Authors: Jung Min Bae, Miri Kim, Ju Hee Han, Solam Lee, Hyun Jeong Ju, Jee Woo Kim, Abdurrahman Almurayshid, Chong Won Choi
Journal: British Journal of Dermatology (2022)

Dear Editor, Levodopa, an amino acid precursor of dopamine and melanin, has been widely used to treat patients with Parkinson disease. Although the incidence of levodopa‐induced cutaneous adverse reactions has not been fully evaluated, recent studies have revealed that melanocyte‐associated skin adverse reaction is the most common.1 Cases of darkening of white hair following levodopa therapy for Parkinson disease have been reported.2 Notably, in vitro studies have revealed the protective effect of levodopa on neuronal cells.3 Therefore, we speculated that levodopa may exert a protective effect on melanocytes and could prevent vitiligo development. We conducted a nationwide, population‐based, case–control study to investigate the association between levodopa use and vitiligo development using the Korean National Health Insurance (NHI) claims database. We first identified all patients with vitiligo aged ≥ 40 years who met a physician at least four times between January 2007 and December 2017 with a diagnosis of vitiligo (vitiligo group). The control individuals had no history of vitiligo and were propensity score matched for age, sex and insurance type. We identified levodopa use in both groups before the first visit date when vitiligo was diagnosed (in the vitiligo group) and conducted conditional logistic regression analyses to explore the association of levodopa use and vitiligo development. All analyses were conducted using SAS software (version 9·4; SAS Institute, Cary, NC, USA). This study was approved by the institutional review board of St Vincent’s Hospital (VC17ZESI0090).
PP35. NEUTROPHIL LYMPHOCYTE COUNT RATIO (NLCR) IN PREDICTING THE HISTOLOGICAL GRADE OF PAEDIATRIC CNS TUMOURS
Authors: Dr Fozia Saeed, Mr Jamie Wilson, Mr Atul Tyagi, Mr John Goodden, Mr Gnanamurthy Sivakumar, Dr Martin Elliott, Prof Alan Melcher, Mr Paul Chumas
Journal: Neuro-Oncology (2017)

Neutrophil lymphocyte count ratio (NLCR) in predicting the histological grade of paediatric CNS tumours INTRODUCTION: Neutrophil Lymphocyte Count Ratio (NLCR) is an established prognostic marker for renal, lung and colorectal carcinomas, and has been suggested to be predictive of histological grade in adult intrinsic primary brain tumours. The purpose of this study was to determine the prognostic impact of pre-operative NLCR in paediatric CNS tumours, in view of disease specific survival and also the prognostic impact of pre-operative NLCR in paediatric CNS tumours stratified by intrinsic subtypes. METHODS: Retrospective analysis at a single centre. Patients less than 18 years old at the time of surgery who underwent tumour-related procedures from 2006–2015. Craniopharyngiomas, recurrent tumours, previous bone marrow transplants and metastases were excluded. Pre-operative NLCRs (collected before the diagnosis of intracranial pathology, and before administration of steroids) were matched with histological diagnosis for each patient. Post-operative NLCR was also recorded where possible. RESULTS: A total of 112 paediatric patients (71 males and 41 females) of an average age 8 ± 4 years, with a diagnosis of primary intrinsic CNS tumours had pre-operative NLCR that could be matched to final histological grade. WHO Grade 1 and 2 tumours (‘low grade’, n=53) had a mean NLCR of 2.42 (95% CI 1.81–3.02) compared to a mean NLCR of 3.56 (95% CI 2.73–4.79) for Grade 3 and 4 tumours (‘high grade’, n=59), which was statistically significant (p=0.035). One-way ANOVA showed a statistically significant variance for NLCR between each grade of tumour. The NLCR for Medulloblastoma was significantly higher (4.2) compared to the low grade cohort (2.42) which was statistically significant (p=0.006). Further analysis of the medullobalstomas showed NLCR for metastatic (n=8, 5.15) and non-metastatic (n=16, 4.9) tumours to have no difference between them (p=0.56). CONCLUSION: Our preliminary results are consistent with published literature on adult tumours and suggest that a larger pre-operative NLCR may correlate with a higher final histological grade in paediatric CNS tumours. Sub-group analysis showed that both metastatic and non-metastatic medulloblastomas have a significantly higher NLCR than low grade CNS tumours.