tbuckley/cabot-search huggingface dataset:
Severe early hepatitis B reactivation in a patient receiving anti-CD19 and anti-CD22 CAR T cells for the treatment of diffuse large B-cell lymphoma
Authors: Jia Wei, Xiaojian Zhu, Xia Mao, Liang Huang, Fankai Meng, Jianfeng Zhou
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Hepatitis B virus (HBV) reactivation is commonly seen in HBsAg-positive hematologic patients undergoing immunosuppressive chemotherapy. Little is known about the risk of HBV reactivation after chimeric antigen receptor T-cell (CAR T) immunotherapy for the treatment of refractory/relapsed malignant B-cell lymphoma. <h3>Case presentation</h3> We report a patient who underwent antiviral prophylaxis for 26 months and who discontinued treatment by herself 1 month after the sequential infusion of two specific, third-generation anti-CD19 and anti-CD22 CAR T cell immunotherapies for refractory/relapsed diffuse large B-cell lymphoma. Remission of the primary disease was achieved after two and half months, but she was admitted with a 7-day history of vomiting, jaundice, itching and dark urine. After excluding other possible causes of acute liver damage, HBV reactivation was suspected. HBV-DNA was 4,497,000 IU/mL at that time. Following the reintroduction of entecavir, a decline in the HBV-DNA copies was observed, but ALT, AST and bilirubin were elevated, and there was no improvement of the clinical conditions. She passed away because of hepatic encephalopathy and multiple organ dysfunction syndrome 40 days after admission. <h3>Conclusions</h3> Our study provides the first report of the severe, early reactivation of an inactive HBsAg carrier after CAR T cell therapy in DLBCL. <h3>Trial registration</h3> ChiCTR-OPN-16008526.
Institutional-based prospective molecular profiling of advanced solid tumours in Hong Kong: A report of 253 cases
Authors: H. Loong, C. Chow, K. Ho, J. Fung, J. Koh, T.-C. Chan, L.K.S. Leung, W. Yeo, B.B.Y. Ma, S.L. Chan, E.P. Hui, K.W.C. Lee, A.C.Y. Wong, D.C.M. Lam, K.C.W. Wong, S.-T. Mok, K.-F. To
Journal: Annals of Oncology (2019)
Results from a focus group evaluating TrialTALK, a designed conversation to facilitate cancer treatment shared decision making.
Authors: Toby Christopher Campbell, Erin Kennedy, Selina Schmocker
Journal: Journal of Clinical Oncology (2019)

34 Background: Cancer treatment decision making involves timely, high-risk, shared decision-making conversations between patients, their families, and their oncologists. These conversations are a prime target for a carefully designed, easy to interpret approach to facilitate preference-sensitive decision-making. The TrialTALK approach has two core elements: a verbal approach and a pen &amp; paper diagram. The diagram includes the diagnosis with prognostic implications, available treatment options along with estimates for efficacy and anticipated impact on daily life. The verbal conversation corresponds to the diagram and includes a phrase to encourage deliberation and empathic responses. Here, we report the results of a focus group conducted in Toronto comparing two approaches to a cancer decision making conversation. Methods: Our focus group was comprised of 9 patients, all with incurable malignancy. They observed a live reading of an actual transcript of a cancer treatment decision making conversation between a patient and oncologist who presented three options: observation, chemotherapy, and a clinical trial. The investigators re-organized the conversation, reusing as many words as possible, into the TrialTALK framework. No new information was introduced. After watching each scene, participants discussed and rated the conversation for information needs and indicated the decision. Results: Three (33%) said rated the standard conversation as meeting their informational needs while 7/9 (78%) reported needs were met by the designed approach. Decision making preferences following the conversations are shown in the table. Patients reported feeling the physician in the designed conversation was more prepared; they felt greater trust and confidence; they valued the paper diagram; they felt more empowered and engaged in the decision. Conclusions: A designed conversation may improve patient understanding, influence decision making, while also enhancing the patient-physician relationship. Clinical trial information: NCT03656276. [Table: see text]
Oral steroids in asthma: a double-edged sword
Authors: Mina Gaga, Eleftherios Zervas
Journal: European Respiratory Journal (2019)

<b>There is poor evidence on the benefits of long-term systemic steroid use in asthma while the risks of morbidity and mortality are high. Systemic steroids should be a last resort and should be withdrawn in non-responders.</b>http://bit.ly/343fs3T
EAU–ESMO consensus statements on the management of advanced and variant bladder cancer—an international collaborative multi-stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees
Authors: A. Horwich, M. Babjuk, J. Bellmunt, H.M. Bruins, T.M. De Reijke, M. De Santis, S. Gillessen, N. James, S. Maclennan, J. Palou, T. Powles, M.J. Ribal, S.F. Shariat, T. Van Der Kwast, E. Xylinas, N. Agarwal, T. Arends, A. Bamias, A. Birtle, P.C. Black, B.H. Bochner, M. Bolla, J.L. Boormans, A. Bossi, A. Briganti, I. Brummelhuis, M. Burger, D. Castellano, R. Cathomas, A. Chiti, A. Choudhury, E. Compérat, S. Crabb, S. Culine, B. De Bari, W. DeBlok, P.J.L. De Visschere, K. Decaestecker, K. Dimitropoulos, J.L. Dominguez-Escrig, S. Fanti, V. Fonteyne, M. Frydenberg, J.J. Futterer, G. Gakis, B. Geavlete, P. Gontero, B. Grubmüller, S. Hafeez, D.E. Hansel, A. Hartmann, D. Hayne, A.M. Henry, V. Hernandez, H. Herr, K. Herrmann, P. Hoskin, J. Huguet, B.A. Jereczek-Fossa, R. Jones, A.M. Kamat, V. Khoo, A.E. Kiltie, S. Krege, S. Ladoire, P.C. Lara, A. Leliveld, E. Linares-Espinós, V. Løgager, A. Lorch, Y. Loriot, R. Meijer, M. Carmen Mir, M. Moschini, H. Mostafid, A.-C. Müller, C.R. Müller, J. N’Dow, A. Necchi, Y. Neuzillet, J.R. Oddens, J. Oldenburg, S. Osanto, W.J.G. Oyen, L. Pacheco-Figueiredo, H. Pappot, M.I. Patel, B.R. Pieters, K. Plass, M. Remzi, M. Retz, J. Richenberg, M. Rink, F. Roghmann, J.E. Rosenberg, M. Rouprêt, O. Rouvière, C. Salembier, A. Salminen, P. Sargos, S. Sengupta, A. Sherif, R.J. Smeenk, A. Smits, A. Stenzl, G.N. Thalmann, B. Tombal, B. Turkbey, S. Vahr Lauridsen, R. Valdagni, A.G. Van Der Heijden, H. Van Poppel, M.D. Vartolomei, E. Veskimäe, A. Vilaseca, F.A. Vives Rivera, T. Wiegel, P. Wiklund, A. Williams, R. Zigeuner, J.A. Witjes
Journal: Annals of Oncology (2019)
Who is at risk for palliative care misconceptions and how do we address them? A mixed-methods study of metastatic lung cancer patients.
Authors: Laurie McLouth, Jennifer Gabbard, Beverly J Levine, Chandylen L Nightingale, Kate Furgurson, Thomas Lycan, William J. Petty, Kathryn E. Weaver
Journal: Journal of Clinical Oncology (2019)

67 Background: A major misperception of palliative care (PC) is that it is only for people who are about to die. We recently identified this misperception as a barrier to PC in metastatic non-small cell lung cancer (mNSCLC) patients, patients who should all receive early PC per guidelines. The goal of this study was to assess patient characteristics associated with misperceptions about PC and to elicit patient perspectives on how to address them. Methods: We conducted a mixed-methods study of mNSCLC patients on immunotherapy or chemo-immunotherapy. A survey assessed sociodemographics, health literacy, and PC misperceptions. Semi-structured interviews queried perceptions of PC, experiences discussing PC with providers, and reactions to our institutional definition of PC. Qualitative data from interviews were analyzed using directed content analysis approach. Results: Sixty patients (Mean age = 63, 40% male; 18% African American, 45% inadequate health literacy) completed the survey. Twelve of the survey participants (Mean age = 65, 50% male, 25% African American, 67% inadequate health literacy; 50% with caregivers participating) also completed a semi-structured interview. Quantitative survey results showed equating PC with death and/or hospice did not differ based on gender, health literacy, rural vs. urban residence, or time since diagnosis (p’s &gt; .05). Qualitative results showed patients and caregivers consistently associated PC with death (e.g., “the next step to the graveyard”) and hospice. Though some patients noted differences between our institution’s definition of PC and their perceptions (e.g., “delivered at any stage”), the definition did not increase interest and sometimes reinforced misperceptions (e.g., “See, that's a death spiral”). To address misconceptions, patients and caregivers suggested distinguishing PC from end of life and hospice, presenting it positively, and discussing it early into treatment. Conclusions: Lung cancer patients may associate PC with death even if they have adequate health literacy. Commonly used definitions of PC may not quell patient fears. PC needs to be presented as a positive service to patients early into treatment.
Overall survival in patients with EGFRm+ NSCLC receiving sequential afatinib and osimertinib: Updated analysis of the GioTag study
Authors: M.J. Hochmair, A. Morabito, D. Hao, C.-T. Yang, R.A. Soo, J.C.-H. Yang, R. Gucalp, B. Halmos, L. Wang, A. Märten, T. Cufer
Journal: Annals of Oncology (2019)
Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treatment (ICON8): primary progression free survival analysis results from a GCIG phase 3 randomised controlled trial
Authors: Andrew R Clamp, Elizabeth C James, Iain A McNeish, Andrew Dean, Jae-Weon Kim, Dearbhaile M O'Donnell, Jane Hook, Christopher Coyle, Sarah Blagden, James D Brenton, Raj Naik, Tim Perren, Sudha Sundar, Adrian D Cook, Gosala S Gopalakrishnan, Hani Gabra, Rosemary Lord, Graham Dark, Helena M Earl, Marcia Hall, Susana Banerjee, Rosalind M Glasspool, Rachel Jones, Sarah Williams, Ann Marie Swart, Sally Stenning, Mahesh Parmar, Richard Kaplan, Jonathan A Ledermann
Journal: The Lancet (2019)

Carboplatin and paclitaxel administered every 3 weeks is standard-of-care first-line chemotherapy for epithelial ovarian cancer. The Japanese JGOG3016 trial showed a significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly carboplatin. In this study, we aimed to compare efficacy and safety of two dose-dense weekly regimens to standard 3-weekly chemotherapy in a predominantly European population with epithelial ovarian cancer.
Long‐term effects of Na<sup>+</sup>/Ca<sup>2+</sup> exchanger inhibition with ORM‐11035 improves cardiac function and remodelling without lowering blood pressure in a model of heart failure with preserved ejection fraction
Authors: Uwe Primessnig, Taja Bracic, Jouko Levijoki, Leena Otsomaa, Piero Pollesello, Martin Falcke, Burkert Pieske, Frank R. Heinzel
Journal: European Journal of Heart Failure (2019)

Aims Heart failure with preserved ejection fraction (HFpEF) is increasingly common but there is currently no established pharmacological therapy. We hypothesized that ORM‐11035, a novel specific Na + /Ca 2+ exchanger (NCX) inhibitor, improves cardiac function and remodelling independent of effects on arterial blood pressure in a model of cardiorenal HFpEF. Methods and results Rats were subjected to subtotal nephrectomy (NXT) or sham operation. Eight weeks after intervention, treatment for 16 weeks with ORM‐11035 (1 mg/kg body weight) or vehicle was initiated. At 24 weeks, blood pressure measurements, echocardiography and pressure–volume loops were performed. Contractile function, Ca 2+ transients and NCX‐mediated Ca 2+ extrusion were measured in isolated ventricular cardiomyocytes. NXT rats (untreated) showed a HFpEF phenotype with left ventricular (LV) hypertrophy, LV end‐diastolic pressure (LVEDP) elevation, increased brain natriuretic peptide (BNP) levels, preserved ejection fraction and pulmonary congestion. In cardiomyocytes from untreated NXT rats, early relaxation was prolonged and NCX‐mediated Ca 2+ extrusion was decreased. Chronic treatment with ORM‐11035 significantly reduced LV hypertrophy and cardiac remodelling without lowering systolic blood pressure. LVEDP [14 ± 3 vs. 9 ± 2 mmHg; NXT ( n = 12) vs. NXT + ORM ( n = 12); P = 0.0002] and BNP levels [71 ± 12 vs. 49 ± 11 pg/mL; NXT ( n = 12) vs. NXT + ORM ( n = 12); P &lt; 0.0001] were reduced after ORM treatment. LV cardiomyocytes from ORM‐treated rats showed improved active relaxation and diastolic cytosolic Ca 2+ decay as well as restored NCX‐mediated Ca 2+ removal, indicating NCX modulation with ORM‐11035 as a promising target in the treatment of HFpEF. Conclusion Chronic inhibition of NCX with ORM‐11035 significantly attenuated cardiac remodelling and diastolic dysfunction without lowering systemic blood pressure in this model of HFpEF. Therefore, long‐term treatment with selective NCX inhibitors such as ORM‐11035 should be evaluated further in the treatment of heart failure.
The immune landscape of esophageal cancer
Authors: Tu-Xiong Huang, Li Fu
Journal: Cancer Communications (2019)

Esophageal cancer (EC) seriously threatens human health, and a promising new avenue for EC treatment involves cancer immunotherapy. To improve the efficacy of EC immunotherapy and to develop novel strategies for EC prognosis prediction or clinical treatment, understanding the immune landscapes in EC is required. EC cells harbor abundant tumor antigens, including tumor-associated antigens and neoantigens, which have the ability to initiate dendritic cell-mediated tumor-killing cytotoxic T lymphocytes in the early stage of cancer development. As EC cells battle the immune system, they obtain an ability to suppress antitumor immunity through immune checkpoints, secreted factors, and negative regulatory immune cells. Cancer-associated fibroblasts also contribute to the immune evasion of EC cells. Some factors of the immune landscape in EC tumor microenvironment are associated with cancer development, patient survival, or treatment response. Based on the immune landscape, peptide vaccines, adoptive T cell therapy, and immune checkpoint blockade can be used for EC immunotherapy. Combined strategies are required for better clinical outcome in EC. This review provides directions to design novel and effective strategies for prognosis prediction and immunotherapy in EC.
Irinotecan and cisplatin therapy-induced neutropenia as a prognostic factor in patients with extensive-disease small cell lung cancer
Authors: H. Ishikawa, D. Tsuji, T. Miyagi, Y. Kawasaki, K. Yamamoto, M. Nakao, S. Nakagaki, T. Hayashi, H. Ayuhara, T. Harada, S. Tamaki, A. Maeda, Y. Ohashi, Y. Arakawa, Y. Fujita, Y. Miyamoto, T. Yano, R. Tanaka, K. Itou
Journal: Annals of Oncology (2019)
Brigatinib in Crizotinib-Refractory ALK+ NSCLC: 2-Year Follow-up on Systemic and Intracranial Outcomes in the Phase 2 ALTA Trial
Authors: Rudolf M. Huber, Karin H. Hansen, Luis Paz-Ares Rodríguez, Howard L. West, Karen L. Reckamp, Natasha B. Leighl, Marcello Tiseo, Egbert F. Smit, Dong-Wan Kim, Scott N. Gettinger, Maximilian J. Hochmair, Sang-We Kim, Corey J. Langer, Myung-Ju Ahn, Edward S. Kim, David Kerstein, Harry J.M. Groen, D. Ross Camidge
Journal: Journal of Thoracic Oncology (2019)

We report updated data from a phase 2 randomized study evaluating brigatinib in crizotinib-refractory anaplastic lymphoma kinase-positive NSCLC.Patients were randomized 1:1 to take either oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (arm B), stratified by central nervous system (CNS) metastases and best response to crizotinib. The primary end point was investigator-assessed confirmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included independent review committee (IRC)-assessed progression-free survival (PFS), intracranial PFS (iPFS), and overall survival (OS). Exploratory analyses included CNS versus ex-CNS target lesion response and correlation of depth of response with PFS and OS.Among 222 randomized patients (112 and 110 in arms A and B, respectively), 59 (27%) remained on brigatinib at analysis (median follow-up: 19.6 versus 24.3 months). At baseline, 71% and 67% had brain lesions among A and B arms, respectively. Investigator-assessed confirmed objective response rate was 46% versus 56%. Median IRC-assessed PFS was 9.2 months (95% confidence interval: 7.4-12.8) versus 16.7 months (11.6-21.4). Median OS was 29.5 months (18.2-not reached) versus 34.1 months (27.7-not reached). IRC-confirmed intracranial objective response rate in patients with measurable baseline brain lesions was 50% (13 of 26) versus 67% (12 of 18); median duration of intracranial response was 9.4 versus 16.6 months. IRC-assessed iPFS was 12.8 versus 18.4 months. Across arms, median IRC-assessed PFS was 1.9, 5.5, 11.1, 16.7, and 15.6 months for patients with no, 1%-25%, 26%-50%, 51%-75%, and 76%-100% target lesion shrinkage, respectively. No new safety findings were observed with longer follow-up.Brigatinib (180 mg once daily with lead-in) continues to demonstrate robust PFS, long iPFS and duration of intracranial response, and high intracranial objective response rate in crizotinib-refractory patients. Depth of response may be an important end point to capture in future targeted therapy trials.
Consistency of Recommendations for Evaluation and Management of Hypertension
Authors: Brian S. Alper, Amy Price, Esther J. van Zuuren, Zbys Fedorowicz, Allen F. Shaughnessy, Peter Oettgen, Glyn Elwyn, Amir Qaseem, Ilkka Kunnamo, Urvi Gupta, Deborah D. Carter, Michael Mittelman, Carla Berg-Nelson, Martin Mayer
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Hypertension is very common, but guideline recommendations for hypertension have been controversial, are of increasing interest, and have profound implications. <h3>Objective</h3> To systematically assess the consistency of recommendations regarding hypertension management across clinical practice guidelines (CPGs). <h3>Design, Setting, and Participants</h3> This cross-sectional study of hypertension management recommendations included CPGs that had been published as of April 2018. Two point-of-care resources that provided graded recommendations were included for secondary analyses. Discrete and unambiguous specifications of the population, intervention, and comparison states were used to define a series of reference recommendations. Three raters reached consensus on coding the direction and strength of each recommendation made by each CPG. Three independent raters reached consensus on the importance of each reference recommendation. <h3>Main Outcomes and Measures</h3> The main outcomes were rates of consistency for direction and strength among CPGs. Sensitivity analyses testing the robustness were conducted by excluding recommendation statements that were described as insufficient evidence, excluding single recommendation sources, and stratifying by importance of recommendations. <h3>Results</h3> The analysis included 8 CPGs with a total of 71 reference recommendations, 68 of which had clear recommendations from 2 or more CPGs. Across CPGs, 22 recommendations (32%) were consistent in direction and strength, 18 recommendations (27%) were consistent in direction but inconsistent in strength, and 28 recommendations (41%) were inconsistent in direction. The rate of consistency was lower in secondary analyses. When insufficient evidence ratings were excluded, there was still substantial inconsistency, and a leave-one-out sensitivity analysis suggested the inconsistency could not be attributed to any single recommendation source. Inconsistency in direction was more common for recommendations deemed to be of lower importance (11 of 20 recommendations [55%]), but 17 of 48 high-importance recommendations (35%) had inconsistency in direction. <h3>Conclusions and Relevance</h3> Hypertension is a common chronic condition with widespread expectations surrounding guideline-based care, yet CPGs have a high rate of inconsistency. Further investigations should determine the reasons for inconsistency, the implications for recommendation development, and the role of synthesis across recommendations for optimal guidance of clinical care.
Everything I Really Needed to Know to Be a Clinical Ethicist, I Learned From Elisabeth Kübler-Ross*
Authors: Mark G. Kuczewski
Journal: The American Journal of Bioethics (2019)

I analyze the insights present in Elisabeth Kübler-Ross's seminal work, On Death and Dying that have laid the foundation for contemporary clinical bioethics as it is practiced by clinical ethics consultants. I highlight the landmark insight of Elisabeth Kübler-Ross that listening to dying patients reveals their needs and enables them to enjoy a better death. But more important for contemporary clinical ethics is that the text highlights three tensions that the clinical ethicist must navigate but can never truly resolve. Clinical ethicists must balance: (1) the need to hear the patient's voice with the temptation to overly medicalize the case, (2) helping the patient achieve a better death with enabling the patient to die in the way he or she chooses, and (3) keeping professional distance with engaging the patient in a way that respects the intimacy of the patient's disclosures.
Semisynthetic, self-adjuvanting vaccine development: Efficient, site-specific sortase A-mediated conjugation of Toll-like receptor 2 ligand FSL-1 to recombinant protein antigens under native conditions and application to a model group A streptococcal vaccine
Authors: Zhenghui Xu, Tania Rivera-Hernandez, Oishee Chatterjee, Mark J. Walker, Peter M. Moyle
Journal: Journal of Controlled Release (2019)
The Milroy Lectures on Changes of Type in Epidemic Diseases: Delivered at the Royal College of Physicians
Authors: B. A. Whitelegge
Journal: BMJ (1893)

Xedical Officer to the County Council of the West Riding of Yorkshire.LECTURE II.Diseease of More Stable Type.-Evidence of Change.-ScarletFever.-Small-pox.-Measle8.IT has long been recognised that scarlet fever changes greatly in character, and that while some epidemics are mild, others are severe.In Sydenham's time it was persistently mild.In Dublin, from 1804 to 1834, the epidemics of scarlet fever were of non-fatal type, but after, as well as before this period, they assumed a malignant form.In New York the scarlet fever death-rate, after being low for thirty years, suddenly increased tenfold in 1828-9, and remained high for sixteen years.Very many instances of this kind are on record, but, nevertheless, they are excep- tional, and, as a rule, the changes in type, which are neither rare nor unimportant, are of slower and more orderly Kraus, has now been formally, appointed to the post.THB Chancellor of the Duchy of Lancaster has appointed Dr. Wm. Graham to be a justice of the peace for the borough of Middleton.