tbuckley/cabot-search huggingface dataset:
A TLR3 Ligand Reestablishes Chemotherapeutic Responses in the Context of FPR1 Deficiency
Authors: Julie Le Naour, Peng Liu, Liwei Zhao, Sandy Adjemian, Zsofia Sztupinszki, Julien Taieb, Claire Mulot, Aymeric Silvin, Charles-Antoine Dutertre, Florent Ginhoux, Allan Sauvat, Giulia Cerrato, Francesca Castoldi, Isabelle Martins, Gautier Stoll, Juliette Paillet, Khady Mangane, Cornelia Richter, Oliver Kepp, Maria Chiara Maiuri, Federico Pietrocola, Peter Vandenabeele, Fabrice André, Suzette Delaloge, Zoltan Szallasi, Pierre Laurent-Puig, Jessica Zucman-Rossi, Laurence Zitvogel, Jonathan G. Pol, Erika Vacchelli, Guido Kroemer
Journal: Cancer Discovery (2020)

Abstract For anthracycline-based chemotherapy to be immunogenic, dying cancer cells must release annexin A1 (ANXA1) that subsequently interacts with the pattern recognition receptor, formyl peptide receptor 1 (FPR1), on the surface of dendritic cells (DC). Approximately 30% of individuals bear loss-of-function alleles of FPR1, calling for strategies to ameliorate their anticancer immune response. Here, we show that immunotherapy with a ligand of Toll-like receptor-3, polyinosinic:polycytidylic acid (pIC), restores the deficient response to chemotherapy of tumors lacking ANXA1 developing in immunocompetent mice or those of normal cancers growing in FPR1-deficient mice. This effect was accompanied by improved DC- and T-lymphocyte–mediated anticancer immunity. Of note, carcinogen-induced breast cancers precociously developed in FPR1-deficient mice as compared with wild-type controls. A similar tendency for earlier cancer development was found in patients carrying the loss-of-function allele of FPR1. These findings have potential implications for the clinical management of FPR1-deficient patients. Significance: The loss-of-function variant rs867228 in FPR1, harbored by approximately 30% of the world population, is associated with the precocious manifestation of breast, colorectal, esophageal, and head and neck carcinomas. pIC restores deficient chemotherapeutic responses in mice lacking Fpr1, suggesting a personalized strategy for compensating for the FPR1 defect. This article is highlighted in the In This Issue feature, p. 211
Thrombosis of the Iliac Vein Detected by 64Cu–Prostate-Specific Membrane Antigen (PSMA) PET/CT
Authors: Salvatore Annunziata, Sandra Rea, Luisa Romano, Costanza Mazzone, Silvia Di Traglia, Rosa Sciuto
Journal: Clinical Nuclear Medicine (2020)

An 82-year-old man had a diagnosis of prostate cancer and underwent curative radiotherapy. During the oncological follow-up, the patient showed biochemical relapse and underwent whole-body Cu-prostate-specific membrane antigen PET/CT for restaging purpose. Cu-prostate-specific membrane antigen PET/CT showed a pathological uptake in left iliac venous axis, subsequently confirmed as venous thrombosis.
Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults
Authors: Michael S. Saag, Rajesh T. Gandhi, Jennifer F. Hoy, Raphael J. Landovitz, Melanie A. Thompson, Paul E. Sax, Davey M. Smith, Constance A. Benson, Susan P. Buchbinder, Carlos del Rio, Joseph J. Eron, Gerd Fätkenheuer, Huldrych F. Günthard, Jean-Michel Molina, Donna M. Jacobsen, Paul A. Volberding
Journal: JAMA (2020)

<h3>Importance</h3> Data on the use of antiretroviral drugs, including new drugs and formulations, for the treatment and prevention of HIV infection continue to guide optimal practices. <h3>Objective</h3> To evaluate new data and incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV. <h3>Evidence Review</h3> New evidence was collected since the previous International Antiviral (formerly AIDS) Society–USA recommendations in 2018, including data published or presented at peer-reviewed scientific conferences through August 22, 2020. A volunteer panel of 15 experts in HIV research and patient care considered these data and updated previous recommendations. <h3>Findings</h3> From 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. Monitoring before and during therapy for effectiveness and safety is recommended. Switching therapy for virological failure is relatively rare at this time, and the recommendations for switching therapies for convenience and for other reasons are included. With the survival benefits provided by therapy, recommendations are made for older individuals with HIV. The current coronavirus disease 2019 pandemic poses particular challenges for HIV research, care, and efforts to end the HIV epidemic. <h3>Conclusion and Relevance</h3> Advances in HIV prevention and management with antiretroviral drugs continue to improve clinical care and outcomes among individuals at risk for and with HIV.
Association of Violence Against Female Sex Workers Who Use Drugs With Nonfatal Drug Overdose in Kazakhstan
Authors: Nabila El-Bassel, Andrea Norcini Pala, Trena I. Mukherjee, Tara McCrimmon, Gaukhar Mergenova, Assel Terlikbayeva, Sholpan Primbetova, Susan S. Witte
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Female sex workers (FSWs) who use drugs face increased risk of intimate partner violence (IPV) and nonpartner violence (NPV). The association between violence and drug overdose is unknown. <h3>Objective</h3> To examine the association between IPV, NPV, and nonfatal drug overdose among FSWs who use drugs in Kazakhstan. <h3>Design, Setting, and Participants</h3> This cross-sectional study included 400 adult FSWs in Kazakhstan who reported illicit drug use in the past year, exchanged sex for money or drugs, and reported having unprotected sex in the past 90 days. Baseline data were collected from February 2015 to May 2017 from Project Nova, an HIV prevention study among FSWs who use drugs in Kazakhstan. Data analysis was conducted from April 2019 to March 2020. <h3>Exposures</h3> Lifetime and recent (past 90 day) experiences of physical, sexual, and psychological IPV and NPV using the Revised Conflict Tactics Scale. Subtypes of violence were identified using exploratory factor analysis. <h3>Main Outcomes and Measures</h3> Lifetime and recent incidence of nonfatal overdose; sociodemographic characteristics as well as lifetime and recent sex work and drug use behaviors were also collected. <h3>Results</h3> The 400 participants had a mean (SD) age of 34.1 (8.4) years. Most experienced food insecurity (358 [89.5%]) and homelessness (232 [58.0%]) in the past 90 days; one-third (130 [32.5%]) reported a history of incarceration. Most (359 [89.7%]) experienced some form of violence; 150 (37.5%) reported a lifetime nonfatal overdose, of whom 27 (18.0%) reported nonfatal overdose in the past 90 days. Lifetime severe physical violence (adjusted odds ratio [aOR], 1.27; 95% CI, 1.02-1.59;<i>P</i> = .03), engagement in sex work for more than 10 years (aOR, 2.54; 95% CI, 1.50-4.28;<i>P</i> &lt; .001), and a history of incarceration (aOR, 4.34; 95% CI, 2.58-7.32;<i>P</i> &lt; .001) were associated with greater odds of nonfatal overdose. Engaging in sex work for more than 10 years (aOR, 3.97; 95% CI, 1.36-11.61;<i>P</i> = .01) and a history of incarceration (aOR, 3.63; 95% CI, 1.39-9.48;<i>P</i> = .008) were associated with greater odds of recent nonfatal overdose. <h3>Conclusions and Relevance</h3> In this study, violence against FSWs who use drugs in Kazakhstan was associated with increased odds of nonfatal overdose. Harm reduction programs for women should consider including services to address gender-based violence and the needs of women after incarceration.
Out-of-season increase of puerperal fever with group A Streptococcus infection: a case–control study, Netherlands, July to August 2018
Authors: Jossy van den Boogaard, Susan JM Hahné, Margreet JM te Wierik, Mirjam J Knol, Sooria Balasegaram, Brechje de Gier
Journal: Eurosurveillance (2020)

We observed an increase in notifications of puerperal group A Streptococcus (GAS) infections in July and August 2018 throughout the Netherlands without evidence for common sources. General practitioners reported a simultaneous increase in impetigo. We hypothesised that the outbreak of puerperal GAS infections resulted from increased exposure via impetigo in the community. We conducted a case–control study to assess peripartum exposure to possible, non-invasive GAS infections using an online questionnaire. Confirmed cases were recruited through public health services while probable cases and controls were recruited through social media. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) with logistic regression analysis. We enrolled 22 confirmed and 23 probable cases, and 2,400 controls. Contact with persons with impetigo were reported by 8% of cases and 2% of controls (OR: 3.26, 95% CI: 0.98–10.88) and contact with possible GAS infections (impetigo, pharyngitis or scarlet fever) by 28% and 9%, respectively (OR: 4.12, 95% CI: 1.95–8.68). In multivariable analysis, contact with possible GAS infections remained an independent risk factor (aOR: 4.28, 95% CI: 2.02–9.09). We found an increased risk of puerperal fever after community contact with possible non-invasive GAS infections. Further study of this association is warranted.
Effect of hospital volume on outcome of stage IV pancreatic cancer.
Authors: Suleyman Yasin Goksu, Muhammet Ozer, Busra N Bacik Goksu, Syed Mohammad Ali Kazmi, Nina Niu Sanford, David Hsieh, Aravind Sanjeevaiah, Leticia Khosama, Todd Anthony Aguilera, Muhammad Shaalan Beg
Journal: Journal of Clinical Oncology (2020)

123 Background: The effect of hospital volume on the outcome of stage 4 pancreatic cancer is not well known. We evaluated the effect of hospital volume on time to treatment and survival in patients with stage 4 pancreatic adenocarcinoma (PDAC). Methods: We used the National Cancer Database, including 1,319 hospitals to identify the study population. Adult (≥ 18 years) patients with stage 4 PDAC were included. We excluded the patients who had other histologies, unknown follow-up, and survival of less than 30 days. We categorized the hospital volume as three groups: low- (&lt;25th centile), medium- (25th–75th centile), and high-volume hospitals (HVH) (&gt;75th centile). Time from diagnosis to chemotherapy initiation was classified as early (≤ 6 weeks) or late (&gt; 6 weeks). Kaplan-Meier and Cox regression methods were used to evaluate the overall survival (OS) between HVH and low-volume hospital (LVH) groups. Results: Among 72,531 patients with stage 4 PDAC; 65% received chemotherapy. Patients treated at HVH had higher rates of chemotherapy ( 73% vs. 60%, p&lt;.001), and late chemotherapy initiation ( 27% vs. 20%, p&lt;.001) compared to LVH. Patients at HVH were more likely to be younger, have less comorbidity score, private insurance, treated at the academic center, and need to travel more than 50 miles (all p&lt;.001). Patients treated at HVH had better OS than LVH (6 vs. 4 months, p&lt;.001). In multivariable analysis, HVH was independently associated with better OS versus LVH ( HR 0.79 [0.72-0.87]). In addition, HVH was associated with better OS in patients who received chemotherapy ( HR 0.78 [0.69-0.88]), while early treatment initiation, age, black race, uninsured status was not. Conclusions: Treatment at an HVH is independently associated with improved survival among patients with stage 4 PDAC. Patients seen at HVH had a higher rate of chemotherapy administration but a longer time to treatment initiation. [Table: see text]
細胞表面免疫グロブリン(SIG)、ターミナルデオキシヌクレオチジルトランスフェラーゼ(TDT)および組換え活性化遺伝子1(RAG-1)の同時発現:2症例と派生株化細胞
Authors: Tatsumi E, Nakamura F, Yoneda N, Kawano S, Tani A
Journal: Blood (1994)
Appropriate Analysis of Duration of Response Data in Cancer Trials—Reply
Authors: Michael Weller, Kay Tatsuoka, David A. Reardon
Journal: JAMA Oncology (2020)

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Digital technology for anaphylaxis management impact on patient behaviour: A randomized clinical trial
Authors: Anna Sala‐Cunill, Olga Luengo, Adrian Curran, Nuria Moreno, Moises Labrador‐Horrillo, Mar Guilarte, Mónica Gonzalez‐Medina, Paula Galvan‐Blasco, Victoria Cardona
Journal: Allergy (2020)

Epinephrine is the first-line treatment for anaphylaxis. Patients at risk should always carry an epinephrine autoinjector (EAI). Several EAI gaps have been identified. We sought to evaluate satisfaction using a medical device (digital technology comprising an EAI smart case connected to a mobile APP) with functions that overcome most of the EAI limitations and to determine whether patient behaviour and anaphylaxis management improve with its use.This was a randomized, open-label, crossover clinical trial in a tertiary hospital involving patients with history of anaphylaxis carrying an EAI. The study was conducted in two three-month periods, one with and one without the medical device. The primary endpoint was satisfaction with the medical device. Usability, adherence, anxiety and anaphylaxis episodes were evaluated as secondary endpoints.A total of 100 patients were included (mean age 38.1 years, 74% female), and 95 completed the trial. The satisfaction visual analogue scale (VAS) after using the medical device was higher than before its use (89.1 [95% CI, 60.2-99.1] vs 56.3 [95% CI, 48.1-81.4]; P < .0001). The adherence VAS improved from 59.7 (95% CI, 54.0-65.3) to 88.6 (95% CI, 84.2-92.9) (P < .0001). Overall, 90% patients found the medical device easy to use. Patients' anxiety decreased from 52.2% to 29.3% (P < .001). Seven episodes of anaphylaxis occurred during the study, all in patients without the medical device (P = .025). Eighty-eight per cent of patients felt more involved in the management of anaphylaxis when using the medical device.This is the first clinical trial evaluating digital technology for EAIs, showing a change of behaviour in patients at risk of anaphylaxis, increasing satisfaction, improving adherence, and reducing anxiety, with good usability.
Oncologist- versus hospitalist-led service: Differences in hospital utilization for solid tumor patients.
Authors: Lesley Wu, Minira Aslanova, Haley Hines Theroux, Hsin-hui Huang, Cardinale B. Smith
Journal: Journal of Clinical Oncology (2020)

53 Background: Hospitalists have been practicing alongside oncologists to provide high quality care for hospitalized cancer patients. We examined the differences in hospital utilization and outcomes among solid tumor patients admitted to oncologist-led teams (OT) versus hospitalist-led teams (HT). Methods: We performed a retrospective cohort study of patients with solid tumors admitted to the OT or HT at Mount Sinai Hospital from July to December 2019. We excluded patients less than 18 years of age, primary hematologic malignancies, or admission to intensive care or surgical units. We used the Activity Measure for Post Acute Care (AMPAC) and Charlson Comorbidity Index as a measure of functional ability and illness severity, respectively. We performed bivariate and multivariate analyses comparing differences in length of stay, ICU transfers, palliative care consults, healthcare proxy (HCP) decision, new DNR decision, readmission within 30 days and inpatient mortality by type of admitting service (OT vs HT). Results: A total of 544 patients were identified; 61% (334) admitted to HT. There were significant differences according to race and cancer type (p= 0.001 for both). HT patients had more functional impairment (p&lt;0.0001) and poorer prognosis (p=0.0002). In bivariate analysis, HT had significantly more ICU transfers (OT, 2% vs HT, 8%; p=0.008), new DNR decisions (OT, 7% vs HT, 16%; p=0.002), and inpatient mortality (OT, 4% vs HT, 9%; p=0.02) while OT had significantly more palliative care consults (OT, 45% vs HT, 20%; p&lt;0.0001). Multivariate analysis (Table) demonstrates HT had significantly more new DNR decisions (odds ratio [OR]: 0.46, 95% confidence interval [CI]: 0.23-0.93) and OT had significantly more palliative care consults (OR: 4.01, 95% CI: 2.51-6.43). Conclusions: At our academic hospital, inpatient cancer care led by hospitalists is comparable to that of oncologists despite HT caring for more severely ill oncology patients. From a value perspective, hospitalists facilitating care for hospitalized cancer patients will allow oncologists to maximize ambulatory time and focus on active cancer treatment. [Table: see text]
Health-related quality of life and its predictors in patients receiving first-line treatment for newly diagnosed glioblastoma multiforme in EU5: A real-world study.
Authors: Bryan Bennett, Roelien Postema, Jennifer P. Hall, Abigail Bailey, Lucy Massey, Alex Z Fu
Journal: Journal of Clinical Oncology (2020)

157 Background: This study describes health-related quality of life (HRQoL) and its predictors including the role of O6-methylguanine DNA methyltransferase promoter (MGMT) testing in first-line (1L) patients (pts) with newly diagnosed glioblastoma multiforme (GBM). Methods: Real-world data were drawn from the GBM Disease-Specific Programme – a cross-sectional study administered to medical and neuro-oncologists who provided information on demographic/clinical status and treatment (tx) patterns for their next 4 consulting 1L GBM pts from May to July 2016 in EU5 countries. Pts voluntarily completed self-completion forms (PSCs), comprising the EORTC QLQ-C30, BN20, and EQ-5D-3L. Linear regressions were conducted using QLQ-C30 global health status (GHS), EQ-5D-3L utility, and EQ-5D visual analogue scale (VAS) scores as dependent variables. Demographic and clinical factors were included as independent variables. Statistically significant results with P&lt;0.05 are presented. Results: 279 1L GBM pts completed a PSC, with a mean age 58.7 years old, 63% were male. 68% (n=189) were MGMT-tested with known results, of which 58% (n=110) were methylated and 42% (n=79) unmethylated. Mean GHS was 45.6 (SD=19.4), utility was 0.57 (SD=0.35), and VAS was 53.5 (SD=18.3). All functional domain scores of the QLQ-C30 were below reference values for general brain cancer population, with differences larger than published thresholds for clinical importance. Age &gt;75 years and ECOG score of 2+ were associated with decreased HRQoL. Longer 1L tx duration, stable/responding disease, and receiving care in Germany, Italy, Spain, or UK (vs France) were associated with increased HRQoL. Results were similar for the subset of pts that was MGMT-tested; however, a greater Charlson index score and not receiving steroids (or RT) were associated with increased HRQoL. MGMT status did not appear to be an independent predictor of HRQoL. Conclusions: HRQoL in pts with GBM receiving 1L treatment is poor. Functional domain scores indicate clinically meaningful problems for these patients. Important predictors of HRQoL include age, performance status, time since tx initiation, country of care, comorbidities, and steroid use alongside RT. Results suggest there remains an unmet need in the tx management of GBM.
Mutant SF3B1 promotes AKT- and NF-κB–driven mammary tumorigenesis
Authors: Bo Liu, Zhaoqi Liu, Sisi Chen, Michelle Ki, Caroline Erickson, Jorge S. Reis-Filho, Benjamin H. Durham, Qing Chang, Elisa de Stanchina, Yiwei Sun, Raul Rabadan, Omar Abdel-Wahab, Sarat Chandarlapaty
Journal: Journal of Clinical Investigation (2020)

Mutations in the core RNA splicing factor SF3B1 are prevalent in leukemias and uveal melanoma, but hotspot SF3B1 mutations are also seen in epithelial malignancies such as breast cancer. Although hotspot mutations in SF3B1 alter hematopoietic differentiation, whether SF3B1 mutations contribute to epithelial cancer development and progression is unknown. Here, we identify that SF3B1 mutations in mammary epithelial and breast cancer cells induce a recurrent pattern of aberrant splicing leading to activation of AKT and NF-κB, enhanced cell migration, and accelerated tumorigenesis. Transcriptomic analysis of human cancer specimens, MMTV-cre Sf3b1K700E/WT mice, and isogenic mutant cell lines identified hundreds of aberrant 3' splice sites (3'ss) induced by mutant SF3B1. Consistently between mouse and human tumors, mutant SF3B1 promoted aberrant splicing (dependent on aberrant branchpoints as well as pyrimidines downstream of the cryptic 3'ss) and consequent suppression of PPP2R5A and MAP3K7, critical negative regulators of AKT and NF-κB. Coordinate activation of NF-κB and AKT signaling was observed in the knockin models, leading to accelerated cell migration and tumor development in combination with mutant PIK3CA but also hypersensitizing cells to AKT kinase inhibitors. These data identify hotspot mutations in SF3B1 as an important contributor to breast tumorigenesis and reveal unique vulnerabilities in cancers harboring them.