tbuckley/cabot-search huggingface dataset:
The impact of the COVID-19 pandemicon cancer patients
Authors: L. Rahib, Z. Kaufman, E. V. Monteverdi
Journal: Clinical Cancer Research (2020)

As overwhelmed health care systems are dealing with the COVID-19 pandemic, changes to oncology care havebeen implemented to minimize patients' exposure to the virus  We aim to understand the impact of COVID-19 oncancer patients through a questionnaire completed by cancer patients or their caregivers  From 3/24/2020 to4/15/2020, a total of 112 patients/caregivers completed the questionnaire  Of the 112, 81 (72%) of those whocompleted the survey were the patients themselves, 14 (13%) were caregivers, and for 17 (15%) it was unknown The majority of patients (48%) were between the ages of 50 and 69, 13% were 70-79, and for 22% of the patients, their age was unknown  66 (59%) were females, 30 (27%) were male, and for 14% the sex was unknown  Thirteentypes of cancers were reported;the most common cancer were breast, lung, and colorectal  Most of the participants were from the US (70%) with 12 countries represented, including Italy (7%), Canada (4%), Australia (3%), and theUK (3%)  Of the 112 patients and caregivers who completed the survey, 78 (70%) reported that they or the patientsthey care for were currently receiving cancer treatment  Those not currently receiving cancer treatment reported thelast time they received treatment as far back as March 2008 to March 2020  Canceled or postponed appointmentsdue to COVID-19 were reported by 32 (29%) participants  Thirteen (12%) reported treatment delay because ofCOVID-19  Six patients (5%) were newly diagnosed and had to make a treatment decision about a new cancerdiagnosis during the COVID-19 pandemic  Twenty-one (19%) patients had to make a decision about a treatmentchange  Eighty-three reported on whether COVID-19 affected any treatment decisions they had to make  Of these83, 24 (29%) reported that COVID-19 affected their treatment decision, and 23 gave an explanation  The mostcommon explanations of how COVID-19 affected treatment decisions were “changes to travel for treatment/changein place of treatment,” “changes in travel/living situations/other personal changes,” “changes to surveillance,“changes, delays, or not receiving treatment to decrease risk of COVID-19 infection,” “continued on treatment that isnot working,” and “did not continue to pursue a clinical trial ” Symptoms of COVID-19 (coughing, fever, shortness ofbreath) were reported by 16 (14%) patients and caregivers  Six (5%) patients had COVID-19 testing, with onepatient still awaiting results, and all of the other five tested negative  Increased anxiety about cancer treatment dueto COVID-19 was reported by 72 (64%) participants  Personalized support through follow-ups was implemented inan attempt to help patients relieve some of their anxiety about their cancer treatment  Overall, changes toappointments, treatment delays, and the impact of COVID-19 on treatment decisions were reported by patients andcaregivers  A general sense of uncertainty about appointments and treatment plans was reported
Outcomes of patients with multiplemyeloma with COVID-19 infection
Authors: M. J. Lunski, K. Tawagi, D. Maslov, L. Finn
Journal: Clinical Cancer Research (2020)

Introduction: While many data have been emerging regarding the outcomes of cancer patients infected with SARS-CoV-2 and their increased risk of mortality, emphasis on patients with hematologic malignancies and how they havebeen affected during this pandemic is lacking  Louisiana, particularly New Orleans, one of the pandemic epicenters, has a higher-than-average cancer diagnosis rate of multiple myeloma as well as cancer-related deaths  OchsnerCancer Institute was fortunately prepared for the crisis, which allowed our center to continue taking care of bothinpatients and outpatients as needed during the pandemic  Hence, we accumulated ample data among cancerpatients and the effects of COVID-19  Here we provide novel initial mortality data on multiple myeloma patientsinfected with SARS-CoV-2  Methods: Our retrospective, electronic medical record review included 15 patients with a history of multiplemyeloma who tested positive for SARS-CoV-2 PCR from March 1st to April 30th, 2020  Medical records werereviewed for inpatient/outpatient status of infection, outcome of infection, multiple myeloma disease and treatmenthistory, and history of autologous stem cell transplant  Results: Out of the 15 patients infected, there were 6 deaths (40%)  A total of 11 patients were on active treatment, including all 6 patients who died (54 5%), though active treatment did not appear to be a significant risk factor whencompared to off-therapy patients (p= 103)  Patients older than 65 years seem to be at increased risk of death whencompared to patients less than 65 years of age (p= 011)  Hospitalized patients were more likely to succumb to infection compared to non-hospitalized patients (p= 044)  Of the 15 patients, 4 had a history of autologous stem celltransplant and this was not found to affect mortality (p= 103)  Chronic kidney disease was present in 7 patients anddid not appear to impact mortality (p= 315)  Of these (n=9), 7 patients had hypogammaglobulinemia and 5 of thesepatients died (71 4%)  Overall, 5 of the 6 patients who died were found to have hypogammaglobulinemia (the 6thdeath did not have immunoglobulins eligible for review)  However, the presence of hypogammaglobulinemia did notappear to increase mortality overall (p= 167)  Conclusion: Patients older than 65 years of age with a history of multiple myeloma seem to be at risk of death fromCOVID-19  Interestingly, a history of autologous stem cell transplant did not appear to affect mortality  While thepresence of hypogammaglobulinemia did not affect mortality, its overwhelming finding in the patients who diedwarrants further discussion in the future  Larger studies are needed to expand on these findings and uncover furthercharacteristics to help stratify at-risk patients in the future
Results of a phase Ib study of regorafenib (REG) 80 mg/day plus pembrolizumab (PEMBRO) for first-line treatment of advanced hepatocellular carcinoma (HCC).
Authors: Richard D. Kim, William P. Harris, Max W. Sung, Dirk Thomas Waldschmidt, Roniel Cabrera, Udo Mueller, Flavia Menezes, Tatiane Ishida, Peter R. Galle, Anthony B. El-Khoueiry
Journal: Journal of Clinical Oncology (2021)

323 Background: In a phase Ib study, REG 120 mg/day plus PEMBRO for first-line treatment of advanced HCC showed no unexpected safety signals and encouraging anti-tumor activity. At the maximum tolerated dose (MTD) of REG (120 mg/day), approximately three-quarters of patients (pts) had a REG dose reduction or interruption due to a treatment-emergent adverse event (TEAE). Here, we present preliminary data for the REG 80 mg/day cohort. Methods: This is an ongoing, dose-finding study in pts who had no prior systemic therapy. In the first cohort, pts received REG 120 mg/day orally for 3 weeks on/1 week off plus PEMBRO 200 mg intravenously q 3 weeks. In later cohorts, the REG dose could be escalated (160 mg/day) or reduced (80 mg/day); the PEMBRO dose is fixed. The primary objective is safety and tolerability. Secondary objectives are to define the MTD and recommended phase II dose and assess anti-tumor activity. Results: By July 24, 2020, 16 pts were treated with REG 80 mg/day. Median age was 67 years (range 56–79), 25%/75% were Barcelona Clinic Liver Cancer stage B/C, 100% Child–Pugh A, and 69%/31% had Eastern Cooperative Oncology Group performance status 0/1. Grade (Gr) 3 TEAEs occurred in 8/16 pts (50%) and there were no Gr 4 TEAEs (Table); one pt experienced Gr 5 pneumonitis (not drug related). There were no reports of Gr 3 hand–foot skin reaction or Gr 3 maculopapular rash, and one report (6%) of Gr 3 rash. TEAEs led to a REG dose reduction or interruption in 50% of pts and to a PEMBRO dose interruption in 25% of pts. Median treatment duration (range) including pts ongoing was 4.1 months (0.4–7.1) for REG and 3.8 months (0.03–7.2) for PEMBRO. Of 13 evaluable pts, 2 (15%) had a partial response and 9 (69%) had stable disease (Response Evaluation Criteria in Solid Tumors v1.1); disease control rate was 85%. Conclusions: These preliminary results for the combination of REG 80 mg/day plus PEMBRO for first-line treatment of advanced HCC were consistent with the REG 120 mg/day cohort. The combination showed no unexpected safety signals and encouraging anti-tumor activity. Assessment of REG 80 mg/day plus PEMBRO is ongoing. Clinical trial information: NCT03347292. [Table: see text]
AB0237 National registry for children with juvenile idiopathic arthritis (jia) and systemic connective tissue diseases
Authors: T Garen, M Haugen, O Vinje, D Sørskaar, B Flatø, Ø Førre
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Centre for Rheumatic Diseases is a National Centre for children with JIA and Connective Idiopathic Arthritis. In 1999 we established a registry to increase the knowledge about JIA and Connective Idiopathic Arthritis in addition to insure diagnosis and the treatment of the patients. The registry will also serve as a research database for the centre. <h3>Objectives</h3> <h3>Methods</h3> To get an impression of disease development one uses seven questionnaires covering different areas. The medical part consists of 5 elements; Disease debut and diagnosis, classifications, doctors evaluation of disease activity, use of medicine and eventual side effects, and laboratory results. The parents and if the patients are 15 years or older the patients themselves will fill inn questionnaires covering Child Health Assessment Questionnaire (CHAQ) and the family history. The patients in the registry will be registered ones every year with a tolerance of ± 3 months. The questionnaires have been prepared in the software program TELEFORM, and the data is read automatically with help of a scanner. However, to assure that the data is read correctly they have to be assured by personnel viewing in addition to the programs own verifier program. The data is put in the database program Access and SPSS is used for statistical calculations. When the data of the patients is put into the database we get with the help of TELEFORM?s merging program new questionnaires for each patient to be used at the next registration. <h3>Results</h3> We have until now about 280 patients registered for the first time and 55 of these are also registered for a second time. <h3>Conclusion</h3>
Tuberculosis, COVID-19 and hospital admission: Consensus on pros and cons based on a review of the evidence
Authors: Giovanni Battista Migliori, Dina Visca, Martin van den Boom, Simon Tiberi, Denise Rossato Silva, Rosella Centis, Lia D’Ambrosio, Tania Thomas, Emanuele Pontali, Laura Saderi, H. Simon Schaaf, Giovanni Sotgiu
Journal: Pulmonology (2021)

The scientific debate on the criteria guiding hospitalization of tuberculosis (TB) and COVID-19 patients is ongoing. The aim of this review is to present the available evidence on admission for TB and TB/COVID-19 patients and discuss the criteria guiding hospitalization. Furthermore, recommendations are made as derived from recently published World Health Organization documents, based on Global Tuberculosis Network (GTN) expert opinion. The core published documents and guidelines on the topic have been reviewed. The proportion of new TB cases admitted to hospital ranges between 50% and 100% while for multidrug-resistant (MDR) TB patients it ranges between 85 and 100% globally. For TB patients with COVID-19 the proportion of cases admitted is 58%, probably reflecting different scenarios related to the diagnosis of COVID-19 before, after or at the same time of the active TB episode. The hospital length of stay for drug-susceptible TB ranges from 20 to 60 days in most of countries, ranging from a mean of 10 days (USA) to around 90 days in the Russian Federation. Hospitalization is longer for MDR-TB (50–180 days). The most frequently stated reasons for recommending hospital admission include: severe TB, infection control concerns, co-morbidities and drug adverse events which cannot be managed at out-patient level. The review also provides suggestions on hospital requirements for safe admissions as well as patient discharge criteria, while underlining the relevance of patient-centred care through community/home-based care.
Presence of Minimal Residual Disease at End of Induction in Acute Myeloid Leukemia Is Predictive of Poor Outcome
Authors: Chinmayee Kakirde, Rohan Kodgule, Goutham Raval, Sanjay Talole, Shraddha Kadechkar, Nikhil Rabade, Yajamanam Badrinath, Sitaram Ghogale, Nilesh Deshpande, Shruti Chaudhary, Swapnali Joshi, Russel Mascarenhas, Dhanlaxmi Shetty, Hari Menon, Manju Sengar, Navin Khattry, Hasmukh Jain, Bhausaheb Bagal, Anant Gokarn, Prashant Tembhare, Sumeet Gujral, Papagudi Ganesan Subramanian, Nikhil Patkar
Journal: Blood (2017)
<i>MYCN</i>-Amplified Neuroblastoma Is Addicted to Iron and Vulnerable to Inhibition of the System Xc-/Glutathione Axis
Authors: Konstantinos V. Floros, JinYang Cai, Sheeba Jacob, Richard Kurupi, Carter K. Fairchild, Mayuri Shende, Colin M. Coon, Krista M. Powell, Benjamin R. Belvin, Bin Hu, Madhavi Puchalapalli, Sivapriya Ramamoorthy, Kimberly Swift, Janina P. Lewis, Mikhail G. Dozmorov, John Glod, Jennifer E. Koblinski, Sosipatros A. Boikos, Anthony C. Faber
Journal: Cancer Research (2021)

Abstract MYCN is amplified in 20% to 25% of neuroblastoma, and MYCN-amplified neuroblastoma contributes to a large percent of pediatric cancer–related deaths. Therapy improvements for this subtype of cancer are a high priority. Here we uncover a MYCN-dependent therapeutic vulnerability in neuroblastoma. Namely, amplified MYCN rewires the cell through expression of key receptors, ultimately enhancing iron influx through increased expression of the iron import transferrin receptor 1. Accumulating iron causes reactive oxygen species (ROS) production, and MYCN-amplified neuroblastomas show enhanced reliance on the system Xc- cystine/glutamate antiporter for ROS detoxification through increased transcription of this receptor. This dependence creates a marked vulnerability to targeting the system Xc-/glutathione (GSH) pathway with ferroptosis inducers. This reliance can be exploited through therapy with FDA-approved rheumatoid arthritis drugs sulfasalazine (SAS) and auranofin: in MYCN-amplified, patient-derived xenograft models, both therapies blocked growth and induced ferroptosis. SAS and auranofin activity was largely mitigated by the ferroptosis inhibitor ferrostatin-1, antioxidants like N-acetyl-L-cysteine, or by the iron scavenger deferoxamine (DFO). DFO reduced auranofin-induced ROS, further linking increased iron capture in MYCN-amplified neuroblastoma to a therapeutic vulnerability to ROS-inducing drugs. These data uncover an oncogene vulnerability to ferroptosis caused by increased iron accumulation and subsequent reliance on the system Xc-/GSH pathway. Significance: This study shows how MYCN increases intracellular iron levels and subsequent GSH pathway activity and demonstrates the antitumor activity of FDA-approved SAS and auranofin in patient-derived xenograft models of MYCN-amplified neuroblastoma.
Pharmacological treatment of hyperglycemia in type 2 diabetes
Authors: Simeon I. Taylor, Zhinous Shahidzadeh Yazdi, Amber L. Beitelshees
Journal: Journal of Clinical Investigation (2021)

Diabetes mellitus is a major public health problem, affecting about 10% of the population. Pharmacotherapy aims to protect against microvascular complications, including blindness, end-stage kidney disease, and amputations. Landmark clinical trials have demonstrated that intensive glycemic control slows progression of microvascular complications (retinopathy, nephropathy, and neuropathy). Long-term follow-up has demonstrated that intensive glycemic control also decreases risk of macrovascular disease, albeit rigorous evidence of macrovascular benefit did not emerge for over a decade. The US FDA’s recent requirement for dedicated cardiovascular outcome trials ushered in a golden age for understanding the clinical profiles of new type 2 diabetes drugs. Some clinical trials with sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP1) receptor agonists reported data demonstrating cardiovascular benefit (decreased risk of major adverse cardiovascular events and hospitalization for heart failure) and slower progression of diabetic kidney disease. This Review discusses current guidelines for use of the 12 classes of drugs approved to promote glycemic control in patients with type 2 diabetes. The Review also anticipates future developments with potential to improve the standard of care: availability of generic dipeptidylpeptidase-4 (DPP4) inhibitors and SGLT2 inhibitors; precision medicine to identify the best drugs for individual patients; and new therapies to protect against chronic complications of diabetes.
SAT0583 DIPEPTIDYL PEPTIDASE-4 AND RISK OF PSORIASIS IN PATIENTS WITH TYPE 2 DIABETES
Authors: W. S. Chen, Y. S. Chang, C. Y. Tsai, C. C. Chang
Journal: Annals of the Rheumatic Diseases (2020)

Background: The risk of psoriasis in diabetic patients has rarely been explored. Objectives: This study aimed to investigate the association between dipeptidyl peptidase-4 (DPP4) inhibitors and the risk of psoriasis in type 2 diabetes mellitus (T2DM) patients. Methods: We conducted a population-based propensity score-matched cohort study on the basis of Taiwan’s National Health Insurance Research Database that included initiators of combination therapy with DPP4i (DPP4i plus metformin) and sulfonylurea (sulfonylurea plus metformin). Psoriasis (PSO) was identified with ≥2 diagnoses. Diabetes complications severity index (DCSI) was calculated. A total of 22721 DPP4 initiator and 227684 sulfonylurea initiator were identified. A 1:10 matched-pair cohort based on propensity score(PS) was created. PS-stratified Cox proportional hazards models compared the risk of PSO in DPP4i versus sulfonylurea initiator within 2 years, controlling for potential confounders. Results: After propensity score matching, 9962 patients with T2DM starting DPP4i combination therapy and 39848 starting sulfonylurea combination therapy were selected. The incidence rate of PSO was lower in DPP4i group (188/100000 person- years) than in sulfonylurea group (467/100000 person-years). Risks of incident psoriasis were significantly lower in the DPP4i group versus sulfonylurea with the PS-stratified HR of 0.422 (95% CI 0.273 to 0.716). Conclusion: DPP4i plus metformin was associated with a reduced risk of psoriasis than sulfonylurea plus metformin. These findings merit further investigation. Disclosure of Interests: None declared
An Immunomodulatory Miniaturized 3D Screening Platform Using Liquefied Capsules
Authors: Sara Nadine, Clara R. Correia, João F. Mano
Journal: Advanced Healthcare Materials (2021)

Abstract A critical determinant of successful clinical outcomes is the host's response to the biomaterial. Therefore, the prediction of the immunomodulatory bioperformance of biomedical devices following implantation is of utmost importance. Herein, liquefied capsules are proposed as immunomodulatory miniaturized 3D platforms for the high‐content combinatorial screening of different polymers that could be used generically in scaffolds. Additionally, the confined and liquefied core of capsules affords a cell‐mediated 3D assembly with bioinstructive microplatforms, allowing to study the potential synergistic effect that cells in tissue engineering therapies have on the immunological environment before implantation. As a proof‐of‐concept, three different polyelectrolytes, ranging in charge density and source, are used. Poly(L‐lysine)‐, alginate‐, and chitosan‐ending capsules with or without encapsulated mesenchymal stem/stromal cells (MSCs) are placed on top of a 2D culture of macrophages. Results show that chitosan‐ending capsules, as well as the presence of MSCs, favor the balance of macrophage polarization toward a more regenerative profile, through the up‐regulation of anti‐inflammatory markers, and the release of pro‐regenerative cytokines. Overall, the developed system enables the study of the immunomodulatory bioperformance of several polymers in a cost‐effective and scalable fashion, while the paracrine signaling between encapsulated cells and the immunological environment can be simultaneously evaluated.
Variable 131I Activity in Renal Stone in a Patient With Thyroid Cancer
Authors: Shihong Liu, Li Chen, Deping Zhang, Chengjian Cao, Fuqiang Shao
Journal: Clinical Nuclear Medicine (2021)

A 42-year-old woman underwent 131I radiotherapy for thyroid papillary cancer. A focal elevated 131I activity in the right kidney was revealed on the initial whole-body posttherapeutic images, which was located in the region of a renal stone. However, on the follow-up 131I images acquired 6 months later, there was no longer any increased activity in the region of this stone, which had moved into right ureter. Our case indicates that the 131I activity accumulated in the region of urinary stone is due to stagnated radioactive urine rather than due to the stone per se.