tbuckley/cabot-search huggingface dataset:
Prescription Drug Monitoring Program Mandates and Opioids Dispensed Following Emergency Department Encounters for Patients With Sickle Cell Disease or Cancer With Bone Metastasis
Authors: Hao Zhang, Austin S. Kilaru, Zachary F. Meisel, Yuhua Bao
Journal: JAMA (2021)

This study examines the association between prescription drug monitoring program mandates and changes in opioids dispensed to patients with sickle cell disease or cancer with bone metastasis who presented to the emergency department in 29 US states.
The Expansion of Health Care Services in the US—Reply
Authors: Timothy M. Westmoreland, M. Gregg Bloche, Lawrence O. Gostin
Journal: JAMA (2021)

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Efficacy of HX008 in high microsatellite instability/mismatch repair–defificient (MSI-H/dMMR) solid tumors: Results from a multicenter phase II open-label study.
Authors: Jing Huang, Yan Song, Suxia Luo, Xianli Yin, Enxiao LI, Hui Wang, Yifu He, Zhihui Liu, Qingxia Fan, Xinjun Liang, Yongqian Shu, Yunpeng Liu, Nong Xu, Shu Zhang, Zhixiang Zhuang, Jingdong Zhang, Xiaoge Kou, Fen Wang, Xiaodong Zhu, Shengmian Li
Journal: Journal of Clinical Oncology (2021)

2572 Background: The subsequent treatment choices are limited for the patients with advanced solid tumors who had failed the standard therapies. PD-1 blockade monotherapy demonstrated robust antitumor activity in patients with MSI-H/dMMR. The aim of this study is to identify the efficacy and safety of HX008, an anti-PD-1 monoclonal antibody, in patients with advanced MSI-H/dMMR solid tumors. Methods: Eligible patients were age ≥18 years with histologically/cytologically confirmed advanced MSI-H/dMMR solid tumors, who have failed at least one line of standard systemic therapy. MSI-H/dMMR status was assessed centrally. Patients received HX008 200 mg once every 3 weeks until disease progression, unacceptable toxicity, or patient withdrawal. Radiologic imaging was performed 9 weeks after the first treatment, then every 6 weeks for the first year of therapy, and every 12 weeks thereafter. The primary end point was objective response rate (ORR) per RECIST1.1. Results: One hundred patients were enrolled from October 2018 to December 2020, with a median age of 53 (range 20-74) years. All of the patients were ≥ second-line patients. The most common cancer types were colorectal cancer (N=74) and gastric cancer (N=10). Median follow-up is 8.97 (range 0.03-25.53) months at the time of data cutoff. Among 86 patients who had reached the initial response evaluation, there were 8 CR, 33 PR, 24 SD, 17 PD and 4 NE. ORR was 47.67% (95%CI 36.79%-58.73%), and DCR was 75.58% (95%CI 65.13%-84.20%). ORR and DCR for the 66 colorectal cancer patients were 50% (95%CI 37.43-62.57%) and 75.76% (95%CI 63.64-85.46%). Median PFS was not reached (95%CI 6.18-NR) for all enrolled patients, while the 6-month and 12-month PFS rates were 62.66% (95%CI 50.98%-72.31%) and 52.70% (95%CI 39.96%-63.94%), respectively. Median OS was not reached. Treatment-related adverse events occurred in 77 patients (77%). Twelve patients (12%) had grade 3 or 4 treatment-related adverse events and there were no grade 5 treatment-related adverse events. The grade 3 or 4 treatment-related adverse events with incidence &gt;1% included anemia (2%) and leukopenia (2%). Immune-related adverse events were observed in 15 patients (15%), including hypothyroidism in 9 patients (all were grade 1-2), and hepatitis, hyperglycemia, myocarditis, creatin kinase/creatin kinase MB increased, hypopigmentation of the vulva, rash, each in 1 patient. Conclusions: HX008 as a ≥second-line therapy showed promising efficacy and a manageable safety profile in patients with MSI-H/dMMR advanced solid tumors. Clinical trial information: NCT03704246.
Improving pneumococcal vaccination rates in pediatric acute lymphoblastic leukemia/lymphoblastic lymphoma.
Authors: Simone Chang, Alexandra Cheerva, Michael Angelo Huang, Kerry McGowan, Esther E Knapp, Ashok Raj, Natalie Slone, Jun Zhao, William T Tse, Mustafa Barbour
Journal: Journal of Clinical Oncology (2021)

e18666 Background: Pediatric Acute Lymphoblastic Leukemia/ Lymphoblastic Lymphoma (ALL/LLy) is the most common pediatric cancer. Invasive pneumococcal disease (IPD) is prevalent in this population and the Centers for Disease Control and Prevention recommends pneumococcal vaccination to decrease morbidity and mortality. Despite these recommendations, vaccination rates remain low and the incidence of IPD among children with hematologic malignancy is significantly higher compared to the average pediatric population. An interventional study was designed to improve the vaccination rate and reduce the incidence of IPD in our institution. Methods: A plan-do-study-act (PDSA) model of quality improvement (QI) was used. Chart review at our institute was done for the 6-month period of January 2020 - June 2020 and baseline rates for pneumococcal polysaccharide (PPSV23) vaccination were calculated. Patients were included if they were ≥ 2 years old, diagnosed with ALL/LLy, and undergoing maintenance. A multidisciplinary team performed the root cause analysis. Immunization records were obtained and reviewed and targeted interventions were implemented. The interventions used are outlined in Table. The percentage of pediatric ALL/LLy patients per month in maintenance who received age-appropriate pneumococcal vaccinations was monitored before and after the interventions. Results: Analysis of the 6-month retrospective cohort (n=36) showed a baseline vaccination rate of 5.5%. During the subsequent 6-month phase with interventions, 40 patients were prospectively enrolled. Demographics showed a mean age of 10.2 years (range, 2-21) and a predominantly male (66.7%) cohort. B-cell ALL/LLy comprised the majority (78.9%); the rest included T-cell ALL/LLy and mixed phenotype acute leukemia. As seen in Table, the percentage receiving at least 1 pneumococcal vaccine increased from 5.5% to 84.8% over the first 3 months, this plateaued around 81%. Completion of the series mirrored this and increased to 74.2%. Pre-visit planning and cues proved to be the most helpful interventions. Conclusions: Use of a PDSA model successfully improved pneumococcal vaccination rates in the pediatric ALL/LLy population. We suggest these results can be achieved with planning and implementation of the outlined interventions. [Table: see text]
Challenging the Prognostic Value of MRD: Sequential Tumor-Ablative Conditioning of FA5-Bucy for Ph-Positive Acute Lymphoblastic Leukemia
Authors: Jianda Hu, Min Xiao, Jinhua Ren, Xiaozhu Yang, Yuxin Zhang, Zhizhe Chen, Ting Yang, Haojie Zhu, Issa Hajjially
Journal: Blood (2017)
Maximal Wall Thickness Measurement in Hypertrophic Cardiomyopathy
Authors: Gabriella Captur, Charlotte H. Manisty, Betty Raman, Alberto Marchi, Timothy C. Wong, Rina Ariga, Anish Bhuva, Elizabeth Ormondroyd, Ilaria Lobascio, Claudia Camaioni, Savvas Loizos, Jenade Bonsu-Ofori, Aslan Turer, Vlad G. Zaha, João B. Augutsto, Rhodri H. Davies, Andrew J. Taylor, Arthur Nasis, Mouaz H. Al-Mallah, Sinitsyn Valentin, Diego Perez de Arenaza, Vimal Patel, Mark Westwood, Steffen E. Petersen, Chunming Li, Lijun Tang, Shiro Nakamori, Reza Nezafat, Raymond Y. Kwong, Carolyn Y. Ho, Alan G. Fraser, Hugh Watkins, Perry M. Elliott, Stefan Neubauer, Guy Lloyd, Iacopo Olivotto, Petros Nihoyannopoulos, James C. Moon
Journal: JACC. Cardiovascular imaging (2021)
Rheumatoid arthritis: NICE recommends more treatments for patients with moderate disease
Authors: Jacqui Wise
Journal: BMJ (2021)

Doctors can now prescribe the biological treatments adalimumab, etanercept, and infliximab for patients with moderate rheumatoid arthritis who have not responded to conventional therapies, following updated guidance from the National Institute for Health and Care Excellence (NICE).1 Biological treatments were previously recommended only for patients with severe rheumatoid arthritis.2

NICE reviewed the evidence again because of the availability of biosimilar versions of adalimumab and etanercept and changes in the prices for …
A Series of Patients With Myocarditis Following SARS-CoV-2 Vaccination With mRNA-1279 and BNT162b2
Authors: John B. Dickey, Elisabeth Albert, Mai Badr, Kristin M. Laraja, Laureen M. Sena, David S. Gerson, Jason E. Saucedo, Waqas Qureshi, Gerard P. Aurigemma
Journal: JACC. Cardiovascular imaging (2021)
Perianal disease remains an understudied and difficult complication in leukemia patients.
Authors: Shreya Gupta, Nirav Patil, Emily Steinhagen-Golbig, Benjamin Kent Tomlinson, Sharon Stein, Ronald Charles
Journal: Journal of Clinical Oncology (2021)

e19016 Background: Perianal infection is a rare and poorly understood complication of patients with acute myeloid/lymphocytic leukemia (AML/ALL). With the advancements in oncology, patients are living longer in an immunocompromised state and thus bearing the inherent problems such as infections that arise with it. Perianal infection and its management impacts patients' quality of life as well as interrupts their ongoing oncologic treatment. The optimal treatment strategy for perianal infections in this highly immunocompromised group remains unclear, as does the selection and outcomes of patients for operative intervention. The aim of this study is to identify patient characteristics associated with perianal infection and to delineate outcomes in patients that undergo operative intervention. Methods: The National Inpatient Sample (NIS) database was used to identify hospitalized patients with diagnoses of perianal abscess and AML/ALL between 2007 and 2015. Patient data were weighted to obtain national estimates. Demographics and clinical characteristics were compared between patients with and without perianal disease using Rao-Scott Chi-square test for categorical variables, and weighted simple linear regression for continuous variables. Characteristics and outcomes were compared between patients who underwent operative or non-operative management. Results: There were 12,626 (0.7%) patients with perianal disease among 1,782,778 AML/ALL patient admissions. Patients with perianal disease were more likely to be younger (43.9 (42.5 – 45.3) years, p &lt; 0.001), male (67.4% vs 32.6%, p &lt; 0.001) and white (65.8% vs 54.8%, p &lt; 0.001). Length of stay (18.4 days vs 9 days, p &lt; 0.001) and hospital cost ($54K vs $25K, p &lt; 0.001) were higher in those with perianal disease, but there was no difference in in-hospital mortality (5.5% in those with perianal diseases vs 6.2% in those without, p = 0.150). Greater proportion of patients without perianal disease were discharged to hospice (12.6% patients without perianal disease vs 5.1% patients with perianal disease, p &lt; 0.001). Receiving a surgical intervention did not improve outcomes with respect to in-hospital mortality (5.9% operative vs 5.4 non-operative, p = 0.596), length of stay (20.2 days vs 18.2 days, p = 0.582) or hospital cost ($67K vs $53K, p = 0.525). Conclusions: Perianal disease is a rare but distressing complication in AML/ALL patients associated with longer hospital stays and higher hospital costs. Operative intervention for perianal disease did not reduce rates of in-hospital mortality, length of stay or hospital cost but it does impact the probability of discharge to hospice. Non-operative and operative intervention both remain equivocal in changing the outcomes these patients. Further studies are required to examine these associations and determine best practices for treatment of this condition in this complex patient population.
Impact of the azoximer bromide concomitant therapy on patient outcomes in patients with melanoma.
Authors: Natalya Shendaleva, Aleksei Viktorovich Novik, Anton Zozulya, Tatyana Leonidovna Nekhaeva, Anna Semenova, Gulfiya Midhatovna Teletaeva, Dilorom Khamidovna Latipova, Tatiana Semiglazova, Svetlana Protsenko, Irina Alexandrovna Baldueva
Journal: Journal of Clinical Oncology (2021)

e21574 Background: Immunomodulators are used in the treatment of patients with melanoma. However, their role as anticancer therapeutic agents requires further investigation. Azoximer bromide (AB) is a well-tolerated immunomodulator that has been used in cases of melanoma. We investigated the impact of AB when used concomitantly with other melanoma treatment modalities on the overall survival (OS) and time to progression (TTP). Methods: We reviewed per protocol, a single-center real practice database that included 1,391 patients. Forty-two patients had received AB as a concomitant therapeutic agent. Concomitant medications included immune checkpoint inhibitors, cytokines, vaccines, targeted therapy and surgery alone in the adjuvant or metastatic setting. We built Cox proportional-hazards models for OS and TTP stratified by stage in SPSS v19. All known prognostic factors (LDH, TNM stage and sub-stage, mutations, sex, age, therapy by type, and by immunologic action) were included in the model along with AB therapy. Known factors were separated from unknown (AB therapy) by different variable blocks. A step forward method was used for model construction. Results: Significant (p &lt; 0.05) factors to emerge in the OS model were LDH (Hazards ration [HR]: 1.458 for high LDH), sub-stage (HR: 1.718 for M1b-d sub-stage), BRAF mutation (HR: 0.698 if present), current therapy type (HR: 0.501 for immune checkpoint inhibitors (ICI), HR: 0.656 for targeted therapy (TT), HR: 1.275 for systemic immunotherapy, HR: 0.825 per added method for complex treatment, HR: 0.605 for surgery), previous treatment (HR: 0.778 for ICI, HR: 1.207 for single-agent chemotherapy, HR 1.176 for targeted or local treatment, HR: 1.315 for combination chemotherapy, HR: 2.039 for immunosuppressive factors reduction methods), male sex (HR: 1.204) and AB therapy (HR: 0.475). Significant factors in the TTP model were LDH (HR: 1.348 for high LDH), sub-stage (HR: 1.434 for B-D sub-stage), current therapy type (HR: 0.432 for (ICI), HR: 0.541 for TT, HR: 0.692 per added method for complex therapy HR: 0.705 for surgery), previous therapy (HR: 0.789 for ICI), male sex (HR: 1.167) and AB therapy (HR: 0.478). Conclusions: The addition of AB to standard therapy in melanoma appears to be an independent favorable prognostic factor. Prospective, randomized, clinical trials are needed to investigate these findings further.
Assessing the Subclonal Genetic Landscape of KMT2A -Rearranged Infant Acute Lymphoblastic Leukemia By Single-Cell Genomics
Authors: Mattias Pilheden, Axel Hyrenius Wittsten, Veronica Gonzalez-Pena, Helena Sturesson, Michael P Walsh, Guangchun Song, Hanne Vibeke Marquart, Birgitte Lausen, Anders Castor, Jinghui Zhang, James R. Downing, Jing Ma, Charles Gawad, Anna K. Andersson
Journal: Blood (2017)
Outcomes of KRAS mutated, EGFR mutated, ALK mutated and wildtype patients in non-small cell lung cancer brain metastases.
Authors: Yasmeen Rauf, Vineeth Tatineni, Patrick joseph Oshea, Xuefei Jia, David M. Peereboom, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2021)

e21028 Background: Non-small cell lung cancer (NSCLC) is the most common primary tumor leading to brain metastases. Multiple genetic markers have been profiled in NSCLC patients for potential targeted therapies. EGFR is mutated in up 50% of NSCLCs, while ALK is mutated in around 4-7%. KRAS is the most commonly overexpressed marker, seen in up to 85% of all lung cancers. In this retrospective study, we evaluated the overall survival (OS) and progression-free survival (PFS) between NSCLCBM patients with KRAS mutations, ALK mutations, EGFR mutations, and wildtype. Methods: NSCLCBM patients diagnosed between 2010 and 2019 were analyzed. We collected information regarding molecular marker status, systemic therapies, and date of progression. We defined OS as the date of diagnosis of brain metastases to the date of last follow-up or death. OS and PFS were estimated by the Cox proportional model. Results: We found a total of 2989 NCSLCBM patients, 184 were KRAS mutated, 68 had an ALK gene rearrangement, 184 were EGFR mutated, and 1469 were wildtype. The respective median age was 64.3 years, 64.5 years, 58.2 years, and 64.2 years. Females made up 61.8% of KRAS-positive, 51.8% of ALK-positive, 63% of EGFR-positive, and 46.4% of wildtype patients. The median OS (mOS) in patients who were KRAS-positive, ALK-positive, EGFR-positive, and wildtype were 43.3 months, 119.2 months, 57.9 months, and 33.1 months, respectively. The median PFS (mPFS) for the same cohort was 38.0 months, 112.4 months, 55.3 months, and 30.5 months, respectively. ALK-positive patients showed statistically significant mOS (p-value (p) &lt; 0.001) and mPFS (p = 0.002) when compared to EGFR-positive, KRAS-positive, and wildtype patients. Conclusions: Molecular mutations serve as both prognostic predictors and alternative targeted therapies for NSCLCBM treatment. Our retrospective study showed improved mOS and mPFS in NSCLCBM patients with ALK rearrangements when compared to patients with EGFR mutations, KRAS mutations, and the wildtype. While these results looked at patient outcomes with specific tumor markers, further investigation needs to be done regarding outcomes of specific therapies in each cohort, as well as, intracranial lesion response.
Molecular classification and diagnostics of upper urinary tract urothelial carcinoma
Authors: Yoichi Fujii, Yusuke Sato, Hiromichi Suzuki, Nobuyuki Kakiuchi, Tetsuichi Yoshizato, Andrew T. Lenis, Shigekatsu Maekawa, Akira Yokoyama, Yasuhide Takeuchi, Yoshikage Inoue, Yotaro Ochi, Yusuke Shiozawa, Kosuke Aoki, Kenichi Yoshida, Keisuke Kataoka, Masahiro M. Nakagawa, Yasuhito Nannya, Hideki Makishima, Jimpei Miyakawa, Taketo Kawai, Teppei Morikawa, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Genta Nagae, Masashi Sanada, Eiji Sugihara, Taka-Aki Sato, Tohru Nakagawa, Masashi Fukayama, Tetsuo Ushiku, Hiroyuki Aburatani, Satoru Miyano, Jonathan A. Coleman, Yukio Homma, David B. Solit, Haruki Kume, Seishi Ogawa
Journal: Cancer Cell (2021)
Humoral Response after SARS-CoV-2 mRNA Vaccination in a Cohort of Hemodialysis Patients and Kidney Transplant Recipients
Authors: Clément Danthu, Sébastien Hantz, Arthur Dahlem, Marion Duval, Bacary Ba, Manon Guibbert, Zhour El Ouafi, Séverine Ponsard, Insaf Berrahal, Jean-Michel Achard, Frédérique Bocquentin, Vincent Allot, Jean-Philippe Rerolle, Sophie Alain, Fatouma Touré
Journal: Journal of the American Society of Nephrology (2021)

Kidney transplant recipients and patients receiving hemodialysis are immunocompromised populations that are prioritized for COVID-19 vaccination but were excluded from clinical trials of SARS-CoV-2 mRNA vaccines. Antibody titers and rates of seroconversion after vaccination are lower among patients with CKD and those taking immunosuppressants compared with controls. Data are lacking regarding their humoral response to vaccination to prevent COVID-19.This investigation of early serological response after COVID-19 vaccination with the Pfizer/BioNTech (BNT162b2) mRNA vaccine included 78 patients undergoing hemodialysis, 74 kidney transplant recipients, and seven healthy controls. We recorded data from the medical file for various clinical parameters, including response to hepatitis B vaccination, and measured antibody titers against SARS-CoV-2 at 0, 14, 28, 36, and 58 days after the first injection.In controls, we detected antibodies at a positive level (>13 arbitrary units per ml; AU/ml) at day 14 postinjection, which increased progressively to peak at day 36 (1082 AU/ml; interquartile range [IQR], 735.0-1662.0). Patients undergoing hemodialysis had lower titers that peaked at day 58 (276 AU/ml; IQR, 83.4-526.0). We detected a positive antibody level in only three transplant recipients at day 36. In patients on hemodialysis, those aged <75 years had a higher antibody response versus those aged >75 years, and serum albumin and Kt/V were positively correlated with serological response (P<0.04 and P<0.0, respectively); nonresponders to HBV vaccine had the lowest anti-SARS-CoV-2 antibody titers.Our results suggest that the postvaccination humoral response is strongly inhibited by immunosuppressant therapy in kidney transplant recipients, and is reduced by the uremic condition in patients undergoing hemodialysis.