tbuckley/cabot-search huggingface dataset:
Efect of ALD518, a humanized anti-IL-6 antibody, on lean body mass loss and symptoms in patients with advanced non-small cell lung cancer (NSCLC): Results of a phase II randomized, double-blind safety and efficacy trial.
Authors: J. R. Rigas, M. Schuster, S. V. Orlov, B. Milovanovic, K. Prabhash, J. T. Smith
Journal: Journal of Clinical Oncology (2010)

7622 Background: ALD518 is a humanized anti-IL-6 antibody being developed for the treatment of anemia, cachexia, and fatigue. The primary objective of the study was to determine the efficacy and safety of ALD518. Methods: 124 patients (pts) with advanced NSCLC, ECOG 0-3, weight loss in the preceding 3 months of >5% body weight, hemoglobin >7g/dl and C-reactive protein (CRP) > 10 mg/L were dosed. Pts were randomized to 1 of 4 treatment groups (∼30/group). Placebo or ALD518 80 mg, 160 mg, or 320 mg was administered i.v. every 8 weeks. Pts were followed up for 24 weeks. Data included FACIT-F, FACT-L, body composition (DEXA), lab safety tests (LSTs) and adverse events (AEs). Results: 29 pts completed the study, 52 died of progressive disease, 5 withdrew because of AEs, and 38 failed to complete every visit. There were no DLTs or infusion reactions. 84 pts had serious AEs of which 1 was deemed possibly related to administration of ALD518 (rectal hemorrhage). Enough patients remained in the study up to week 12 to make a statistical comparison valid. The mean (±SD) values for lean body mass (LBM), FACT-L lung symptom subscale (LCS) and FACIT-F fatigue subscale (FS) are shown in the Table. Conclusions: ALD518 given to pts with NSCLC was safe and well tolerated. ALD518 improved the lung symptom score, reversed fatigue, and there was less loss of LBM (-0.19 kg on ALD518 vs. -1.50 kg on placebo). There were no major safety signals or infusion reactions related to the administration of ALD518. Visit n LBM (kg) n FACT-LLCS n FACIT-FFS ALD518 Pre-dose 93 41.90 (±9.35) 93 13.3 (±4.3) 93 20.5 (±9.6) (pooled) Week 2 - - 79 15.1 (±3.8)* 79 22.9 (±10.5)** Week 12 35 41.71 (±10.29) 39 15.6 (±5.2) 39 23.8 (±10.9) Placebo Pre-dose 31 41.58 (±10.74) 31 13.7 (±3.4) 31 21.9 (±9.6) Week 2 - - 29 14.1 (±4.2) 29 21.3 (±11.1) Week 12 20 40.08 (±11.00) 21 15.2 (±3.9) 21 22.1 (±13.2) * p ≤ 0.0006. ** p = 0.025 (paired t-test compared to baseline). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Alder Biopharmaceuticals Inc. Alder Biopharmaceuticals Inc. Alder Biopharmaceuticals Inc.
Screening Programs for SARS-CoV-2 Infections on a University Campus — Austin, Texas, September 30–November 30, 2020
Authors: Kayleigh J. Nerhood, Emily R. James, Allen Hardin, James E. Bray, Terrance S. Hines, Amy E. Young, Darlene Bhavnani
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Colleges and universities in the United States have relied on various measures during the COVID-19 pandemic to prevent transmission of SARS-CoV-2, the virus that causes COVID-19, including implementing testing programs (1-3).These programs have permitted a safer return to campus for students by identifying infected persons and temporarily isolating them from the campus population (2,3).The University of Texas at Austin (UT Austin) implemented COVID-19 prevention measures in Fall 2020* including the following testing programs: clinic-based diagnostic testing, voluntary community screening, and targeted screening (testing of specific student populations in situations of increased transmission risk).During September 30-November 30, 2020, UT Austin students participated in tests for SARS-CoV-2, which resulted in the detection of 401 unique student cases of COVID-19 from among 32,401 tests conducted.† Among students who participated in one targeted screening program for students attending campus events, 18 (37.5%) of 48 infected students were asymptomatic at the time of their positive test result compared with 45 (23%) of 195 students identified through community testing and nine (5.8%) of 158 students identified through clinic-based testing.Targeted screening also identified a different population of students than did clinic-based and community testing programs.Infected students tested through targeted screening were more likely to be non-Hispanic White persons (chi square = 20.42;p<0.03), less likely to engage in public health measures, and more likely to have had interactions in settings where the risk for SARS-CoV-2 transmission is higher, such as restaurants, gyms, and residence halls.In addition to clinic-based SARS-CoV-2 testing at colleges and universities, complementary testing programs such as community and targeted screening might enhance efforts to identify and control SARS-CoV-2 transmission, especially among asymptomatic persons and disproportionately affected populations that might not otherwise be reached.During September 30-November 30, 2020, UT Austin employed the following SARS-CoV-2 testing programs: 1) clinic-based diagnostic testing administered by University Health Services for persons who were symptomatic or reported * https://protect.utexas.edu/† A COVID-19 case was defined as a positive SARS-CoV-2 nucleic acid amplification test or antigen test result.
General practice rescue package: a mutually agreed framework of negotiation is essential
Authors: Richard Pratt
Journal: BMJ (2021)

For those of us working in primary care there’s much about the Royal College of GPs vision for tackling current challenges1 that appeals: increased GP numbers, reduction of bureaucratic burden, large numbers of non-doctors, enhanced physical and digital infrastructure, and making sure we are able to influence the direction of integrated care systems (ICSs).

There is value too in …
Reliability and Safety of Bedside Blind Bone Biopsy Performed by a Diabetologist for the Diagnosis and Treatment of Diabetic Foot Osteomyelitis
Authors: Florine Féron, Gauthier Péan de Ponfilly, Louis Potier, Diane-Cécile Gauthier, Laurence Salle, Marie Laloi-Michelin, Anne-Lise Munier, Hervé Jacquier, Tiphaine Vidal-Trécan, Jean-Baptiste Julla, Aurélie Carlier, Yawa Abouleka, Nicolas Venteclef, Nathalie Grall, Frédéric Mercier, Jean-Pierre Riveline, Éric Senneville, Jean-François Gautier, Ronan Roussel, Jean-Philippe Kevorkian
Journal: Diabetes Care (2021)

OBJECTIVE Bone biopsy (BB) performed by a surgeon or an interventional radiologist is recommended for suspicion of osteomyelitis underlying diabetic foot ulcer (DFU). To facilitate its practice, we developed a procedure allowing bedside blind bone biopsy (B4) by a diabetologist. RESEARCH DESIGN AND METHODS We conducted a three-step observational study consisting of a feasibility and safety phase (phase 1) to assess the success and side effects of B4, a validity phase (phase 2) to compare DFU outcomes between positive (B4+) and negative (B4−) bone cultures, and a performance phase (phase 3) to compare B4 with the conventional surgical or radiological procedure basic bone biopsy (B3). Primary end points were the presence of bone tissue (phase 1) and complete DFU healing with exclusive medical treatment at 12 months (phases 2 and 3). RESULTS In phase 1, 37 consecutive patients with clinical and/or radiological suspicion of DFU osteomyelitis underwent B4. Bone tissue was collected in all patients with few side effects. In phase 2, a B4+ bone culture was found in 40 of 79 (50.6%) participants. Among B4+ patients, complete wound healing after treatment was 57.5%. No statistical difference was observed with patients with B4− bone culture not treated with antibiotics (71.8%, P = 0.18). In phase 3, the proportion of patients with positive BB was lower in B4 (40 of 79, 50.6%) than in B3 (34 of 44, 77.3%, P &amp;lt; 0.01). However, complete healing was similar (64.6% vs. 54.6%, P = 0.28). No difference in rate of culture contamination was observed. CONCLUSIONS B4 is a simple, safe, and efficient procedure for the diagnosis of DFU osteomyelitis with a similar proportion of healing to conventional BB.
A large outbreak of giardiasis in a municipality of the Bologna province, north-eastern Italy, November 2018 to April 2019
Authors: Davide Resi, Stefania Varani, Anna Rosa Sannella, Alessandra M De Pascali, Margherita Ortalli, Giovanna Liguori, Marco Benvenuti, Maria C Re, Roberta Pirani, Luciana Prete, Claudia Mazzetti, Muriel Musti, Lorenzo Pizzi, Tiziana Sanna, Simone M Cacciò
Journal: Eurosurveillance (2021)

Giardiasis, the disease caused by the flagellate Giardia duodenalis (syn. G.lamblia, G. intestinalis), is the most commonly reported among the five food- and waterborne parasitic diseases under mandatory surveillance in 24 EU countries. From November 2018 to April 2019, an outbreak of giardiasis occurred in a municipality of the Bologna province, in north-eastern Italy. Microscopy and immunochromatography identified cysts and antigens, respectively, of the parasite in stool samples of 228 individuals. Molecular typing of 136 stool samples revealed a vast predominance (95%) of G. duodenalis assemblage B. Investigations into potential sources indicated tap water as the most likely vehicle of infection, although cysts were not detected in water samples. Control measures mostly aimed at preventing secondary transmission by informing citizens about the outbreak, and by treatment of patients with anti-parasitic drugs. This is the first documented human outbreak of giardiasis in Italy; its investigation has highlighted the difficulties in the timely detection and management of this parasite, which is often overlooked as a cause of human gastroenteritis. The long and variable incubation time, absence of specific symptoms and a general lack of awareness about this pathogen contributed to delay in diagnosis.
Association of Blood Donor Sex and Age With Outcomes in Very Low-Birth-Weight Infants Receiving Blood Transfusion
Authors: Ravi M. Patel, Joshua Lukemire, Neeta Shenvi, Connie Arthur, Sean R. Stowell, Martha Sola-Visner, Kirk Easley, John D. Roback, Ying Guo, Cassandra D. Josephson
Journal: JAMA Network Open (2021)

<h3>Importance</h3> There are conflicting data on the association between blood donor characteristics and outcomes among patients receiving transfusions. <h3>Objective</h3> To evaluate the association of blood donor sex and age with mortality or serious morbidity in very low-birth-weight (VLBW) infants receiving blood transfusions. <h3>Design, Setting, and Participants</h3> This is a cohort study using data collected from 3 hospitals in Atlanta, Georgia. VLBW infants (≤1500 g) who received red blood cell (RBC) transfusion from exclusively male or female donors were enrolled from January 2010 to February 2014. Infants received follow-up until 90 days, hospital discharge, transfer to a non–study-affiliated hospital, or death. Data analysis was performed from July 2019 to December 2020. <h3>Exposures</h3> Donor sex and mean donor age. <h3>Main Outcomes and Measures</h3> The primary outcome was a composite outcome of death, necrotizing enterocolitis (Bell stage II or higher), retinopathy of prematurity (stage III or higher), or moderate-to-severe bronchopulmonary dysplasia. Modified Poisson regression, with consideration of covariate interactions, was used to estimate the association between donor sex and age with the primary outcome, with adjustment for the total number of transfusions and birth weight. <h3>Results</h3> In total, 181 infants were evaluated, with a mean (SD) birth weight of 919 (253) g and mean (SD) gestational age of 27.0 (2.2) weeks; 56 infants (31%) received RBC transfusion from exclusively female donors. The mean (SD) donor age was 46.6 (13.7) years. The primary outcome incidence was 21% (12 of 56 infants) among infants receiving RBCs from exclusively female donors, compared with 45% (56 of 125 infants) among those receiving RBCs from exclusively male donors. Significant interactions were detected between female donor and donor age (<i>P</i> for interaction = .005) and between female donor and number of transfusions (<i>P</i> for interaction &lt; .001). For the typical infant, who received a median (interquartile range) of 2 (1-3) transfusions, RBC transfusion from exclusively female donors, compared with male donors, was associated with a lower risk of the primary outcome (relative risk, 0.29; 95% CI, 0.16-0.54). The protective association between RBC transfusions from female donors, compared with male donors, and the primary outcome increased as the donor age increased, but decreased as the number of transfusions increased. <h3>Conclusions and Relevance</h3> These findings suggest that RBC transfusion from female donors, particularly older female donors, is associated with a lower risk of death or serious morbidity in VLBW infants receiving transfusion. Larger studies confirming these findings and examining potential mechanisms are warranted.
Effector differentiation downstream of lineage commitment in ILC1s is driven by Hobit across tissues
Authors: Christin Friedrich, Renske L. R. E. Taggenbrock, Rémi Doucet-Ladevèze, Gosia Golda, Rebekka Moenius, Panagiota Arampatzi, Natasja A. M. Kragten, Katharina Kreymborg, Mercedes Gomez de Agüero, Wolfgang Kastenmüller, Antoine-Emmanuel Saliba, Dominic Grün, Klaas P. J. M. van Gisbergen, Georg Gasteiger
Journal: Nature Immunology (2021)
A stem cell-derived ovarian regenerative patch restores ovarian function and rescues fertility in rats with primary ovarian insufficiency
Authors: Sichen Zhang, Dashuai Zhu, Zhenhua Li, Ke Huang, Shiqi Hu, Halle Lutz, Mengjie Xie, Xuan Mei, Junlang Li, Genevieve Neal-Perry, Shaowei Wang, Ke Cheng
Journal: Theranostics (2021)

Primary ovarian insufficiency (POI) normally occurs before age 40 and is associated with infertility. Hormone replacement therapy is often prescribed to treat vasomotor symptom, but it cannot restore ovarian function or fertility. Stem cell therapy has been studied for the treatment of POI. However, the application of live stem cells has suffered from drawbacks, such as low cell retention/engraftment rate, risks for tumorigenicity and immunogenicity, and lack of off-the-shelf feasibility.
Dialytic Therapy for Irreversible Uremia
Authors: Thomas Manis, Eli A. Friedman
Journal: New England Journal of Medicine (1979)

(Second of Two Parts)Modifications of Hemodialysis TherapySequential Ultrafiltration and DialysisPatients on MH rely mainly on ultrafiltration to remove salt and water that accumulate despite insensible losses and residual urine output. During hemodialysis, a hydrostatic pressure gradient is created across the dialysis membrane so that fluid and solutes leave the blood and enter the dialysate. Ultrafiltrative extraction of 1 to 2 liters in four to six hours usually entails no difficulty. Removing large volumes of fluid (over 3 liters) from patients who gain excessive weight between dialyses may be poorly tolerated and is frequently associated with hypotension or . . .
Oral examinations---equal opportunities, ethnicity, and fairness in the MRCGP Commentary: Oral exams---get them right or don't bother
Authors: C. Roberts
Journal: BMJ (2000)

# Oral examinations—equal opportunities, ethnicity, and fairness in the MRCGP {#article-title-2} Oral examinations are widely used in undergraduate and postgraduate medical examinations, including those for membership of royal colleges. In recent years the validity and reliability of oral examinations have been questioned and they have been dropped from many assessment programmes.1-4 The Royal College of General Practitioners has a tradition of reflecting on these issues and has improved its membership examination through the careful selection and training of examiners, the use of an examination blueprint, the development of clear questions and criteria for marking, and continuing discussion of techniques and problems.5 None the less, the debate about equal opportunities and the possible discriminatory outcomes of the examination has continued as failed candidates and their colleagues have suggested that their lack of success might be due to racial discrimination. #### Ethnographic and sociolinguistic discourse analysis Discourse analysis is the detailed study of language in use. Unlike many traditional ways of assessing communication that use coding schemes, it examines the finegrained detail of interaction—sentence structure, intonation, taking turns, and non-verbal communication—as well as the content18 Ethnographic method involves observing and interviewing, taking the informant's perspective as far as possible in order to understand the cultural and communicative patterns which inform his or her behaviour and perceptions Sociolinguistics examines variety in language use and, in this context, studies how differences in talk and self presentation can lead to negative assessments and possibly to racial discrimination A study in 1995 showed that although the success rate among British Asians was not in question, Asian doctors trained abroad did less well than other groups.6 They were relatively more likely to fail the written examination, which meant that they were not called for the oral examination. But even among those called for the oral examination, ethnic minority candidates trained overseas did proportionately less well. The examination board's commitment to … Correspondence to: A Esmail
Validation of a high performing blood test for multiple major cancer screenings.
Authors: Linhao Xu, Jun Wang, Weifeng Ma, Xin Liu, Sihui Li, Siyu Chen, Qian Hu, Ting Yang, Zhujia Ye, Zhiwei Chen, Jianbing Fan
Journal: Journal of Clinical Oncology (2021)

10561 Background: Early detection at the localized stage is pivotal for the successful treatment of various cancer types. Although several cancers already have routine screening approaches, the comprehensive utilities are impeded for various reasons, e.g., low accuracy, high cost, limited availability of required facilities, especially in the developing countries. Therefore, an accurate, cost-effective, and non-invasive test for multiple major cancer screening is in high demand. We previously reported a cfDNA methylation test, which can detect five major cancer types with high specificity and sensitivity, especially at the early stage (stage I). These five major cancers, including lung cancer (LC), breast cancer (BC), colorectal cancer (CRC), gastric cancer (GC), and esophageal cancer (EC), account for 56% of new cancer cases and 60% of cancer-related deaths yearly in China. Here, we report the result in an independent cohort as a further validation of this multi-cancer screening test. Methods: The high-throughput targeted methylation profiling platform, Aurora, was used to analyze the plasma samples from an independent retrospective cohort containing 505 healthy controls and ̃200 cases for each cancer type. A locked model based on our previous pilot study (reported in AACR 2020 and 2021) was applied to this data set to assess the overall performance. Results: The Area Under Curves (AUC) of the classifier for LC, BC, CRC, GC and EC are 97.3%, 96.2%, 92.0%, 94.0% and 93.5%, respectively. At a fixed specificity of 99%, the sensitivities for LC, BC, CRC, GC and EC are 84%, 75%, 82%, 85% and 78%, respectively. Conclusions: A methylation blood test for five major cancer screening has been validated in a large retrospective cohort. Its high sensitivity for each cancer type, especially at the early stage (stage I), and easy to use suggests it can be implemented in real clinical world. A large prospective clinical trial is undergoing to further validate this test in asymptomatic populations.
SO-24 Circulating tumor DNA variant allelic fraction as a surrogate for disease burden estimation in patients with RAS wild-type metastatic colorectal cancer: A secondary endpoint of the VALENTINO study
Authors: P. Manca, S. Corallo, S. Lonardi, F. Corti, C. Antoniotti, L. Procaccio, V. Smiroldo, G. Tomasello, R. Murialdo, F. Pagani, G. Randon, A. Martinetti, E. Sottotetti, M. Prisciandaro, M. Ambrosini, A. Raimondi, F. Morano, F. Pietrantonio
Journal: Annals of Oncology (2021)
Unilateral Leg Swelling in a Young Woman
Authors: Jason P. Lambden, Denise K. Au, Aarati D. Didwania
Journal: JAMA Oncology (2021)

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Endoscopic submucosal dissection combined with clip for closure of gastrointestinal fistulas including those refractory to previous therapy
Authors: Pierre Lafeuille, Timothée Wallenhorst, Alexandru Lupu, Jérémie Jacques, Thomas Lambin, Marine Camus, Clara Yzet, Thierry Ponchon, Florian Rostain, Jérôme Rivory, Fabien Subtil, Mathieu Pioche
Journal: Endoscopy (2021)

Gastrointestinal (GI) fistula is a life-threatening condition and a therapeutic challenge. Endoscopic approaches include mucosal abrasion, clip closure, or stent diversion, with moderate success rates in the long term. We assessed whether fistula endoscopic submucosal dissection with clip closure (FESDC) could lead to complete resolution of fistulas even after failure of previous endoscopic therapy.Patients with GI fistulas, including those with previous failed treatment, were retrospectively included. The primary outcome was long-term (> 3 months) success of fistula healing. Secondary outcomes included technical success, safety, and factors associated with FESDC success.23 patients (13 refractory 57 %) were included. Tight immediate sealing was achieved in 19 patients (83 %; 95 % confidence interval [CI] 61 %-95 %). Long-term closure was achieved in 14 patients (61 %; 95 %CI 39 %-80 %), with median follow-up of 20 months. Complications occurred in two patients (9 %). Previous local malignancy (P = 0.08) and radiotherapy (P = 0.047) were associated with a higher risk of failure.This novel FESDC strategy was demonstrated to be safe and feasible for permanent endoscopic closure of GI fistulas. Further studies are warranted to determine the place of this technique in the management of chronic GI fistula.
Germline Genetic Testing for Women With Breast Cancer: Shifting the Paradigm From Whom to Test to Whom NOT to Test
Authors: Nadine Tung, Neelam Desai
Journal: Journal of Clinical Oncology (2021)

Approximately 3% of patients with breast cancer have a pathogenic or likely pathogenic variant (mutation) in a high-risk breast cancer gene, such as BRCA1 and BRCA2 (BRCA1/2) and PALB2, which increases breast cancer risk more than fourfold. 1,2Another roughly 3% have a germline mutation in a moderatepenetrance breast cancer gene, such as ATM or CHEK2, which confers a two-to threefold increased risk of breast cancer.