tbuckley/cabot-search huggingface dataset:
P14.13 Severe hematological toxicity during chemoradiation for glioblastoma: Identification of clinical and pharmacological risk factors and consequences for the individual patient
Authors: N Grun, C A den Otter, M Sintemaartensdijk, J Osinga, F E L van den Elzen, A N van der Vegt, J de Haan, A M E Bruynzeel, M E van Linde, T J Postma, M Schuur, P C de Witt Hamer, F Y F L De Vos, J J C Verhoeff, J L M Jongen, B I Lissenberg-witte, M C M Kouwenhoven
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Besides early tumour progression, standard first-line radiation with concurrent and adjuvant temozolomide in de novo glioblastoma patients is abrogated frequently by severe haematological toxicity. This leads to treatment delays with unknown effect on efficacy and to more hospital visits with increased disease burden. In the present study, we identified clinical and pharmacological risk factors for temozolomide induced severe hematological toxicity. Furthermore, we describe the burden of toxicity for patients and evaluate the effect of severe toxicity on prognosis. METHODS A retrospective cohort study of adult patients with a histological confirmed glioblastoma (n=363), treated with standard treatment regimen at the Brain Tumor Center Amsterdam between 2000 and -2020. Severe haematological toxicity was defined as a CTCAE (version 5.0) grade ≥3. We used Pearson Chi-Square test to analyze differences in patient characteristics between the groups (no vs. severe toxicity) and paired samples T- Test to analyze fluctuations in cell counts. Univariate and multivariate logistic regression were used to identify patient- and treatment characteristics associated with severe hematological toxicity. Cox Proportional Hazards models were used to estimate Hazard Ratio’s for the association between survival and severe hematological toxicity. RESULTS Female gender (OR 8.05, 95%CI 2.96–21.89, p&amp;lt;0.001) and older age (age &amp;gt; 70 years; OR 2.44, 95%CI 1.12–5.31, p=0.025) were independent risk factors for severe toxicity. Concurrent and adjuvant temozolomide was discontinued in respectively 56% and 35% of the patients. In general, patients with severe hematological toxicity had a treatment delay of 22 ± 48 days. Of all patients with severe hematological toxicity during chemoradiation, 96% developed toxicity after ≥4 weeks of treatment (p&amp;lt;0.001). Females who received highest temozolomide-doses (4th quartile) had a longer survival than females with low cumulative temozolomide doses (1st quartile). Patients, who developed severe toxicity had much more hospital visits (20; range 12–26), and were admitted more frequently to the hospital. Severe haematological toxicity was not related to survival (HR 1.04; 95%CI 0.74–1.45). CONCLUSION Female gender and age &amp;gt;70 years are risk factors for severe hematological toxicity. Severe hematological toxicity relates to temozolomide exposure and results in a significant treatment burden for patients. Low temozolomide exposure results in decreased survival. Patient tailored therapy may result in better treatment outcomes.
RhoA drives actin compaction to restrict axon regeneration and astrocyte reactivity after CNS injury
Authors: Sina Stern, Brett J. Hilton, Emily R. Burnside, Sebastian Dupraz, Emily E. Handley, Jessica M. Gonyer, Cord Brakebusch, Frank Bradke
Journal: Neuron (2021)

An inhibitory extracellular milieu and neuron-intrinsic processes prevent axons from regenerating in the adult central nervous system (CNS). Here we show how the two aspects are interwoven. Genetic loss-of-function experiments determine that the small GTPase RhoA relays extracellular inhibitory signals to the cytoskeleton by adapting mechanisms set in place during neuronal polarization. In response to extracellular inhibitors, neuronal RhoA restricts axon regeneration by activating myosin II to compact actin and, thereby, restrain microtubule protrusion. However, astrocytic RhoA restricts injury-induced astrogliosis through myosin II independent of microtubules by activating Yes-activated protein (YAP) signaling. Cell-type-specific deletion in spinal-cord-injured mice shows that neuronal RhoA activation prevents axon regeneration, whereas astrocytic RhoA is beneficial for regenerating axons. These data demonstrate how extracellular inhibitors regulate axon regeneration, shed light on the capacity of reactive astrocytes to be growth inhibitory after CNS injury, and reveal cell-specific RhoA targeting as a promising therapeutic avenue.
Quality of Care Before and After Mergers and Acquisitions of Rural Hospitals
Authors: H. Joanna Jiang, Kathryn R. Fingar, Lan Liang, Rachel M. Henke, Teresa P. Gibson
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Rural hospitals are increasingly merging with other hospitals. The associations of hospital mergers with quality of care need further investigation. <h3>Objectives</h3> To examine changes in quality of care for patients at rural hospitals that merged compared with those that remained independent. <h3>Design, Setting, and Participants</h3> In this case-control study, mergers at community nonrehabilitation hospitals in Federal Office of Rural Health Policy–eligible zip codes during 2009 to 2016 in 32 states were identified from Irving Levin Associates and the American Hospital Association Annual Survey. Outcomes for inpatient stays for select conditions and elective procedures were derived from the Healthcare Cost and Utilization Project State Inpatient Databases. Difference-in-differences linear probability models were used to assess premerger to postmerger changes in outcomes for patients discharged from merged vs comparison hospitals that remained independent. Data were analyzed from February to December 2020. <h3>Exposures</h3> Hospital mergers. <h3>Main Outcomes and Measures</h3> The main outcome was in-hospital mortality among patients admitted for acute myocardial infarction (AMI), heart failure, stroke, gastrointestinal hemorrhage, hip fracture, or pneumonia, as well as complications during stays for elective surgeries. <h3>Results</h3> A total of 172 merged hospitals and 266 comparison hospitals were analyzed. After matching, baseline patient characteristics were similar for 303 747 medical stays and 175 970 surgical stays at merged hospitals and 461 092 medical stays and 278 070 surgical stays at comparison hospitals. In-hospital mortality among AMI stays decreased from premerger to postmerger at merged hospitals (9.4% to 5.0%) and comparison hospitals (7.9% to 6.3%). Adjusting for patient, hospital, and community characteristics, the decrease in in-hospital mortality among AMI stays 1 year postmerger was 1.755 (95% CI, −2.825 to −0.685) percentage points greater at merged hospitals than at comparison hospitals (<i>P</i> &lt; .001). This finding held up to 4 years postmerger (DID, −2.039 [95% CI, −3.388 to −0.691] percentage points;<i>P</i> = .003). Greater premerger to postmerger decreases in mortality at merged vs comparison hospitals were also observed at 5 years postmerger among stays for heart failure (DID, −0.756 [95% CI, −1.448 to −0.064] percentage points;<i>P</i> = .03), stroke (DID, −1.667 [95% CI, −3.050 to −0.283] percentage points;<i>P</i> = .02), and pneumonia (DID, −0.862 [95% CI, −1.681 to −0.042] percentage points;<i>P</i> = .04). <h3>Conclusions and Relevance</h3> These findings suggest that rural hospital mergers were associated with better mortality outcomes for AMI and several other conditions. This finding is important to enhancing rural health care and reducing urban-rural disparities in quality of care.
Fully automated magnetically controlled capsule endoscopy for examination of the stomach and small bowel: a prospective, feasibility, two-centre study
Authors: Yu-Feng Xiao, Zhi-Xuan Wu, Song He, Yuan-Yuan Zhou, Yong-Bing Zhao, Jia-Lin He, Xue Peng, Zhao-Xia Yang, Qing-Jian Lv, Huan Yang, Jian-Ying Bai, Chao-Qiang Fan, Bo Tang, Chang-Jiang Hu, Meng-Meng Jie, En Liu, Hui Lin, Anastasios Koulaouzidis, Xiao-Yan Zhao, Shi-Ming Yang, Xia Xie
Journal: The Lancet. Gastroenterology & hepatology (2021)
A quality improvement initiative to increase screening for financial coverage for breast cancer patients to decrease financial toxicity.
Authors: Preethi John, Mary P. Hodges, Gaurav Shah, Umber Dickerson, Julie Dreadin-Pulliam, Julie Smith, Carolyn B. Hendricks, Ashraf Mahmoud Mohamed
Journal: Journal of Clinical Oncology (2021)

259 Background: In April 2021, it was found that 35% of our breast cancer patients seen in the breast surgery and medical oncology clinics had no financial coverage leading to significant financial toxicity at Parkland Memorial Hospital, a safety net hospital for Dallas county in Texas. In addition, only 8% of all our breast cancer patients were financially screened in April 2021. We aimed to increase pre-visit phone calls to financially screen patients within a week of their subsequent visit with a provider from a baseline rate of 8% to 20% for all breast cancer patients in hopes of capturing more unfunded patients and providing appropriate resources. Methods: We used the Institute for Health Improvement (IHI) model as our quality improvement framework. Based on our fish bone and pareto chart analysis, it was discovered that the lack of consistent financial screening was likely due to lack of standardized training across our ancillary staff, lack of standardized processes for financial screening, and lack of education of both providers and patients regarding the financial coverage process. To address these issues, we created a standardized process of financial screening called “pre-visit planning (PVP)” involving a telephone call by our schedulers to breast oncology patients within 1 week of their next visit. Screening included checking financial application status and educating patients on methods of application submission including epic my-chart enrollment. Screening also included checking financial coverage status and if unfunded, a referral to a financial counselor was made. Formal training of staff was performed with mock trial phone calls. We initiated implementation in the breast surgery clinic initially with plans to expand to the medical oncology clinic. Results: At baseline, in April 2021, 300 patients were seen in the breast surgery clinic of which 19 were financially screened (6.3%). Implementation of PVP for all patients in the breast surgery clinic began in May 2021 with data representing 2 weeks of financial screening by our staff. Total number of patients seen over the span of 2 weeks in the breast surgery clinic was 165 of which 59 were financially screened making up 36% of patients. In addition, 8 patients in the breast surgery clinic were screened by a financial counselor increasing the rate of financial screening to 40.6%. Conclusions: We successfully implemented PVP to better assist our patients in several ways including updating their financial coverage, educating them on the financial process, as well as referring them to a financial counselor for additional aid. Increased follow up time is needed to assess the downstream effects of PVP such as increase in financial counselor visits and decrease in unfunded patients.
Mixed evidence on the relationship between socioeconomic position and atopic dermatitis: A systematic review
Authors: Harsimran Bajwa, Mohsen Baghchechi, Mahasin Mujahid, Mi-Suk Kang Dufour, Sinéad M. Langan, Katrina Abuabara
Journal: Journal of the American Academy of Dermatology (2021)
Patient- and provider-level predictors of mortality among patients with metastatic renal cell carcinoma receiving oral anticancer agents.
Authors: Lisa Spees, Michaela Ann Dinan, Bradford E. Jackson, Christopher Baggett, Lauren E. Wilson, Melissa A. Greiner, Deborah Kaye, Tian Zhang, Daniel J. George, Charles D. Scales, Jessica Pritchard, Michael S. Leapman, Cary Philip Gross, Stephanie B. Wheeler
Journal: Journal of Clinical Oncology (2021)

116 Background: It is important to understand how emerging new therapies, such as oral anti-cancer agents (OAAs), diffuse across and can improve outcomes within real-world populations, which include age groups and racial groups not well-represented in clinical trials, such as people older than age 65 and Black patients. Our objectives were to examine whether disparities in mortality persist among patients with metastatic renal cell carcinoma (mRCC) receiving OAAs and whether these disparities may be partially explained by patient’s clinical characteristics or provider-level factors. Methods: We used linked state cancer registry data and multi-payer claims data to identify patients with mRCC who were diagnosed in 2004 through 2015 and had initiated an OAA and survived ≥ 90 days after initiating. Provider data were obtained from North Carolina Health Professions Data System and the National Plan &amp; Provider Enumeration System. A patient’s modal provider was the provider most frequently on claims with a diagnosis code of RCC or metastatic cancer between 2 months prior to and 3 months following the index date. We estimated hazard ratios (HR) and corresponding 95% confidence limits (CL) using Cox proportional hazard models to evaluate which patient demographics, patient clinical characteristics, and provider-level factors were associated with 2-year all-cause mortality. Results: The cohort included 207 patients with mRCC. In unadjusted analyses, public insurance (Medicaid or Medicare), de novo metastatic diagnosis, frailty, polypharmacy, and a visit to a skilled nursing facility were associated with increased all-cause mortality. In multivariable models, clinical variables such as frailty (HR: 1.36, 95% CL: 1.11-1.67) and de novo metastatic diagnosis (HR: 2.63, 95%CL: 1.67-4.16) were associated with higher all-cause mortality. Additionally, Medicare-insured patients continued to have higher all-cause mortality compared to privately insured patients (HR: 2.35, 95% CL: 1.32-4.18). None of the provider-level covariates (i.e., specialization, experience, volume, or practice location) investigated were associated with all-cause mortality. Conclusions: Even when adjusting for age, frailty, and comorbidities, Medicare-insured patient had lower overall survival than privately-insured patients. Patient survival did not differ based on modal provider’s characteristics.
Bedaquiline can act as core drug in a standardised treatment regimen for fluoroquinolone-resistant rifampicin-resistant tuberculosis
Authors: Tom Decroo, Kya Jai Maug Aung, Mohamed Anwar Hossain, Mourad Gumusboga, Nimer Ortuno-Gutierrez, Bouke Catherine De Jong, Armand Van Deun
Journal: European Respiratory Journal (2021)

Previous studies showed that a fluoroquinolone-based short treatment regimen is effective for the treatment of tuberculosis (TB) resistant to the most important first-line TB drug, rifampicin. How to replace the fluoroquinolone in case of resistance to fluroquinolone, the most potent second-line drug, is unknown. Our findings show that replacing a fluoroquinolone by bedaquiline in the same short treatment regimen resulted in an early and sustained treatment response. When linezolid was used to the strengthen the fluoroquinolone-based regimen during the first treatment months the same early effect was not shown. Our findings suggest that bedaquiline, but probably not linezolid, can act as the treatment's core drug and can assure relapse-free cure. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflicts of interest: B.C. de Jong reports grant funding from USAID for the STREAM trial on Bedaquiline for MDR-TB; and membership of a Panacea scientific advisort board, both within the 36 months prior to manuscript submission. All other authors declare no conflicts of interest.
Overcoming Acquired Epigenetic Resistance to BTK Inhibitors
Authors: Arthur L. Shaffer, James D. Phelan, James Q. Wang, DaWei Huang, George W. Wright, Monica Kasbekar, Jaewoo Choi, Ryan M. Young, Daniel E. Webster, Yandan Yang, Hong Zhao, Xin Yu, Weihong Xu, Sandrine Roulland, Michele Ceribelli, Xiaohu Zhang, Kelli M. Wilson, Lu Chen, Crystal McKnight, Carleen Klumpp-Thomas, Craig J. Thomas, Björn Häupl, Thomas Oellerich, Zachary Rae, Michael C. Kelly, Inhye E. Ahn, Clare Sun, Erika M. Gaglione, Wyndham H. Wilson, Adrian Wiestner, Louis M. Staudt
Journal: Blood Cancer Discovery (2021)

Abstract The use of Bruton tyrosine kinase (BTK) inhibitors to block B-cell receptor (BCR)–dependent NF-κB activation in lymphoid malignancies has been a major clinical advance, yet acquired therapeutic resistance is a recurring problem. We modeled the development of resistance to the BTK inhibitor ibrutinib in the activated B-cell (ABC) subtype of diffuse large B-cell lymphoma, which relies on chronic active BCR signaling for survival. The primary mode of resistance was epigenetic, driven in part by the transcription factor TCF4. The resultant phenotypic shift altered BCR signaling such that the GTPase RAC2 substituted for BTK in the activation of phospholipase Cγ2, thereby sustaining NF-κB activity. The interaction of RAC2 with phospholipase Cγ2 was also increased in chronic lymphocytic leukemia cells from patients with persistent or progressive disease on BTK inhibitor treatment. We identified clinically available drugs that can treat epigenetic ibrutinib resistance, suggesting combination therapeutic strategies. Significance: In diffuse large B-cell lymphoma, we show that primary resistance to BTK inhibitors is due to epigenetic rather than genetic changes that circumvent the BTK blockade. We also observed this resistance mechanism in chronic lymphocytic leukemia, suggesting that epigenetic alterations may contribute more to BTK inhibitor resistance than currently thought. See related commentary by Pasqualucci, p. 555. This article is highlighted in the In This Issue feature, p. 549
Menstrual changes after covid-19 vaccination
Authors: Victoria Male
Journal: BMJ (2021)

<h3>Objectives</h3> Low back pain (LBP) is common in rowers and leads to considerable disability and even retirement. The athlete voice can help clinicians to better understand sport-related pain disorders. We aimed to capture the lived experience of LBP in rowers. <h3>Methods</h3> Cross-sectional qualitative study using a grounded theory approach. Adult competitive rowers with a rowing-related LBP history were recruited in Australia and Ireland. Data were collected through interviews that explored: context around the time of onset of their LBP and their subsequent journey, experiences of management/treatment, perspectives around present beliefs, fears, barriers and expectations for the future. <h3>Results</h3> The 25 rowers (12 women/13 men) who participated were aged 18–50 years; they had a mean 12.1 years of rowing experience. They discussed a culture of concealment of pain from coaches and teammates, and fear of being judged as ‘weak’ because of the limitations caused by LBP. They reported fear and isolation as a result of their pain. They felt that the culture within rowing supported this. They reported inconsistent messages regarding management from medical staff. Some rowers reported being in a system where openness was encouraged—they regarded this a leading to better outcomes and influencing their LBP experience. <h3>Conclusions</h3> Rowers’ lived experience of LBP was influenced by a pervasive culture of secrecy around symptoms. Rowers and support staff should be educated regarding the benefits of early disclosure and rowers should be supported to do so without judgement.
Endoscopic Approaches to Obesity Management
Authors: Russell D. Dolan, Allison R. Schulman
Journal: Annual Review of Medicine (2021)

The field of endoscopic bariatric and metabolic therapy has rapidly evolved from offering endoscopic treatment of weight regain following bariatric surgery to providing primary weight loss options as alternatives to pharmacologic and surgical interventions. Gastric devices and remodeling procedures were initially designed to work through a mechanism of volume restriction, leading to earlier satiety and reduced caloric intake. As the field continues to grow, small bowel interventions are evolving that may have some effect on weight loss but focus on the treatment of obesity-related comorbidities. Future implementation of combination therapy that utilizes both gastric and small bowel interventions offers an exciting option to further augment weight loss and alleviate metabolic disease. This review considers gastric devices and techniques including space-occupying intragastric balloons, aspiration therapy, endoscopic tissue suturing, and plication interventions, followed by a review of small bowel interventions including endoluminal bypass liners, duodenal mucosal resurfacing, and endoscopically delivered devices to create incisionless anastomoses.
機能獲得シグナル伝達物質と転写1変異の活性化因子を有する患者における造血幹細胞移植【JST・京大機械翻訳】
Authors: W Leiding Jennifer, Okada Satoshi, Hagin David, Abinun Mario, Shcherbina Anna, N Balashov Dmitry, H D Kim Vy, Ovadia Adi, L Guthery Stephen, Pulsipher Michael, Lilic Desa, A Devlin Lisa, Christie Sharon, Depner Mark, Fuchs Sebastian, van Royen-Kerkhof Annet, Lindemans Caroline, Petrovic Aleksandra, E Sullivan Kathleen, Bunin Nancy, Kilic Sara Sebnem, Arpaci Fikret, Calle-Martin Oscar de la, Martinez-Martinez Laura, Aldave Juan Carlos, Kobayashi Masao, Ohkawa Teppei, Imai Kohsuke, Iguchi Akihiro, M Roifman Chaim, R Gennery Andrew, Slatter Mary, D Ochs Hans, Morio Tomohiro, R Torgerson Troy
Journal: Journal of Allergy and Clinical Immunology (2018)
MHC class II in renal tubules plays an essential role in renal fibrosis
Authors: Yunfeng Zhou, Zhaokang Luo, Chenghui Liao, Rong Cao, Zain Hussain, Jie Wang, Yeting Zhou, Tie Chen, Jie Sun, Zhong Huang, Baohua Liu, Xiaoyan Zhang, Youfei Guan, Tuo Deng
Journal: Cellular and Molecular Immunology (2021)
Inclusion criteria: how NK cells gain access to T cells
Authors: Tonya J. Webb
Journal: Journal of Clinical Investigation (2021)

Natural killer (NK) cells play an important role in host defense against viral infections and malignancy, and their role for regulating other components of the antiviral response is being investigated. In this issue of the JCI, Ali et al. examine the mechanisms by which NK cells migrate into the white pulp and mediate suppression of virus-specific T cells. Herein, the authors show that an acute lymphocytic choriomeningitis virus (LCMV) infection induced a potent type I IFN (IFN-I) response that resulted in the expression of chemokine receptor CXCR3 ligands and permitted NK cell trafficking to T cell zones. Collectively, these findings have broad implications for vaccination strategies and warrant further investigation into the transcriptomic profiles of these regulatory NK cells.
An International Agreement on Pandemic Prevention and Preparedness
Authors: Lawrence O. Gostin, Sam F. Halabi, Kevin A. Klock
Journal: JAMA (2021)

On March 30, 2021, the heads of state of 26 nations, joined by the executive director of the World Health Organization (WHO) and the president of the European Council, called for an international treaty on pandemic prevention and preparedness-the highest level of political action to avert and respond to future health crises. 1 In an historic action, 194 countries passed a World Health Assembly (WHA) resolution to host a special session devoted solely to an international pandemic agreement, now scheduled for November 29, 2021. 2 The WHA special session will be preceded by the United Nations (UN) General Assembly and the G20 group of nations on September 14 and October 30, 2021, respectively.WHO Director-General Tedros Ghebreyesus referred to these 3 events as critical in shaping global health security.