tbuckley/cabot-search huggingface dataset:
‘Finding the right one’
Authors: Abhishek Arvind Zanwar
Journal: Annals of the Rheumatic Diseases (2020)

The authors concluded in the abstract that, 'Our data reveal a need for a waiting period of at least 6 months to perform an MRI-SIJ in postpartum women with back pain'.But 69% of study subjects do not have back pain and are asymptomatic.Though the study is very systematically planned and has achieved its primary aim, the inferences drawn seem a little far-fetched and are applicable to only a limited set of individuals in real life.The fear of overdiagnosing spondyloarthritis (SpA) comes into the picture only when the dedicated sacroiliac joint (SIJ) is ordered, which may not be the case for most of the study population (69%) in real life.So, the study would have been more pragmatic if only subjects with chronic back pain 8/35 (22.85%) were included.Assessment of SpondyloArthritis international Society (ASAS) criteria mandate presence of 'Inflammatory back pain' for more than 3 months before proceeding to MRI-SIJ. 2 So, only 4/35 (11.4%) would have qualified for imaging in real life.It would have been more useful had the authors compared Spondyloarthritis Research Consortium of Canada (SPARCC) scores in individuals with/without inflammatory back pain than just back pain.The number of individuals with 'inflammatory back pain' and the number of individuals showing sacroiliitis and positive SPARCC Score at 1 year are the same (4/35).Whether these are the same subjects or different should be looked into.Also, the data related to acute phase reactants, like C reactive protein, would have added value to the results and analysis.The study definitely emphasises the importance of avoiding overdiagnosis of SpA based on incidental SIJ findings.But, delaying diagnosis in 'true' SpA can lead to the progression of disease, damage accrual and increased disability duration.As evident from the recent population-based study, individuals in the 'imaging arm' (positive findings on MRI) have faster progression from non-radiographic SpA to radiographic SpA. 3 Studies have also shown more delay in diagnosis for women than males. 4he reason for this is, in part, the classical teaching of higher male to female ratio in SpA.But a recent cohort study doesn't show any gender difference. 5So, delaying imaging for 6 months altogether for all postpartum women with back pain seems unjust.Future studies comparing likelihood ratios with MRI findings alone and with the inclusion of inflammatory back pain, acute phase reactants, other SpA features, positive family history and response to non-steroidal anti-inflammatory agents would help us in finding 'The right one' who needs dedicated MRI-SIJ in the postpartum period.
Pd-1 inhibitors plus nab-paclitaxel with S1 (AS) as first line in patients with advanced biliary tract cancer.
Authors: Miaomiao Gou, Liu Tie E, Huan Yan, Haiyan Si, Zhikuan Wang, Niansong Qian, Guanghai Dai
Journal: Journal of Clinical Oncology (2020)

e15195 Background: The way to treat advanced biliary tract cancers (BTCs) including Intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, gallbladder cancer was disappointing. Hence, we explore the efficacy and safety of pd-1 inhibitors plus chemotherapy (nab-paclitaxel with S1, AS) as first line in patients with BTC. Methods: BTC patients from oncology department of Chinese PLA general hospital receiving PD-1 inhibitors with AS or AS alone were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). The second endpoint was objective response rate (ORR), disease control rate (DCR) and safety. Results: 32 patients given pd-1 inhibitors (Pembrolizumab, Nivolumab, Sintilimab, Toripalimab) plus AS and 26 patients used AS alone were included in the study. The median PFS was 5.43m in combined group, significantly longer than the 2.82m with monotherapy alone group (HR 0.46, 95% CI 0.25–0.84, P = 0.01). OS was not matured in the pd-1 inhibitors group. PFS of Intrahepatic cholangiocarcinoma subgroup seemed better than extrahepatic group in the AS group (5.54m VS 2.57m, P = 0.004).however, there was no evidence of difference in intrahepatic group compared the other group in the pd-1 inhibitor group (5.07m vs 5.43m, P = 0.453). liver metastatic was poor predictor of PFS in both Pd-1 combined or not group (2.43m vs 7.63m, P = 0.01; 2.14m vs 5.54m, P = 0.04 ).ORR was 25% and DCR were 84.3% in Pd-1 inhibitor group and ORR was 15.3% and DCR was 69.2% in chemotherapy alone group respectively. No significant difference was seen for ORR and DCR compared between two groups (P = 0.364, P = 0.169). Grade 3 or 4 treatment-related adverse events(AE) in pd-1 inhibitor group were hypothyroidism (n = 3), rash (n = 2), hepatitis (n = 1). No AE related death. Myelosuppression was similar between the anti-PD-1 combination group and the chemotherapy alone group (12.5% and15.3 %, respectively). Conclusions: Anti-PD-1 therapy plus nab-paclitaxel with S1 prolonged the PFS and improved the ORR, DCR compared the nab-paclitaxel with S1 alone in advanced BTC with controllable AE. Further clinical trials were needed and we conduct the phrase II clinic trail of Toripalimab with AS (TSA-01 study) is ongoing (clinical registration number: NCT04027764).
Associations between safety and tolerability and reporting of health-related quality of life in phase III randomized trials in common solid tumors.
Authors: Ramy Saleh, Nick Meti, Domen Ribnikar, Hadar Goldvaser, Alberto Ocana, Arnoud J. Templeton, Bostjan Seruga, Eitan Amir
Journal: Journal of Clinical Oncology (2020)

e19206 Background: Anti-cancer drugs are approved typically on the basis of efficacy and safety as evaluated in phase III randomized trials (RCTs). Health related quality of life (HRQoL) is a direct measure of patient benefit from drugs. Despite this, HRQoL is not reported universally for all anti-cancer drugs. Here we explore associations with reporting of HRQoL data in phase III RCTs in common solid tumors. Methods: We searched ClinicalTrials.gov to identify phase III oncology RCTs evaluating new drugs in adult patients with breast, colorectal, lung, or prostate cancers. We included all completed or active trials that completed accrual between January 1, 2005 and October 31, 2016. Data were extracted from published trials including HRQoL data and toxicity data on toxic death, treatment discontinuation and commonly reported grade 3 or 4 adverse events (AEs). Then, we explored associations between these safety and tolerability measures and the odds of reporting HRQoL data and whether HRQoL were favourable or not. Analysis comprised logistic regression and was performed in SPSS version 25. Results: A total of 377 phase III RCTs were initially identified. After excluding ineligible studies, a total of 143 studies were analysed. All trials (100%) were in the metastatic setting with 79 (55%) being positive trials. 40 (28%) were breast cancer trials, 38 (26%) were focused on evaluating chemotherapy, and 128 (90%) of trials were industry sponsored. 84 (59%) trials reported measuring HRQoL data, however of these, only 47 (56%) reported HRQoL data. In 14 (30%) HRQoL was improved with experimental therapy. There was no association between treatment related death (OR 1.25, 95%CI 0.74-2.12, p = 0.398) or treatment discontinuation (OR 1.12, 95%CI 0.73-1.72, p = 0.61) with reporting of HRQoL data. Associations with grade 3 or 4 AEs are shown in the Table. Conclusions: HRQoL is reported for only around a half of RCTs that collect such data. Reporting of HRQoL is not associated with safety and tolerability of anti-cancer drugs. [Table: see text]
The Predictive Approaches to Treatment effect Heterogeneity (PATH) Statement
Authors: Stuart G. Baker
Journal: Annals of Internal Medicine (2020)

Letters2 June 2020The Predictive Approaches to Treatment effect Heterogeneity (PATH) StatementStuart G. Baker, ScDStuart G. Baker, ScDNational Cancer Institute, Bethesda, Maryland (S.G.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L20-0426 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In discussing effect modeling for heterogeneity of treatment effect, Kent and colleagues (1) restricted their prediction models to include multiplicative treatment-by-covariate interaction terms. An informative alternative is the subpopulation treatment effect pattern plot (STEPP) using a benefit function involving multiple predictive markers (2). To implement the STEPP approach, investigators split the data in a randomized trial into training and test samples.Using the training sample, investigators fit a benefit function on the basis of the predictive markers. Two possible benefit functions are risk difference (for standard treatment trials) and responders-only (for prevention trials with a rare outcome). ...References1. Kent DM, Paulus JK, van Klaveren D, et al. The Predictive Approaches to Treatment effect Heterogeneity (PATH) Statement. Ann Intern Med. 2019;171:34-45. [PMID: 31711134]. doi:10.7326/M18-3667 LinkGoogle Scholar2. Baker SG, Bonetti M. Evaluating markers for guiding treatment. J Natl Cancer Inst. 2016;108. [PMID: 27193772] doi:10.1093/jnci/djw101 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: National Cancer Institute, Bethesda, Maryland (S.G.B.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L20-0426. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Predictive Approaches to Treatment effect Heterogeneity (PATH) Statement David M. Kent , Jessica K. Paulus , David van Klaveren , Ralph D'Agostino , Steve Goodman , Rodney Hayward , John P.A. Ioannidis , Bray Patrick-Lake , Sally Morton , Michael Pencina , Gowri Raman , Joseph S. Ross , Harry P. Selker , Ravi Varadhan , Andrew Vickers , John B. Wong , and Ewout W. Steyerberg The Predictive Approaches to Treatment effect Heterogeneity (PATH) Statement David van Klaveren , Ravi Varadhan , and David M. Kent Metrics Cited byProtocol for the development of a reporting guideline for causal and counterfactual prediction models in biomedicine 2 June 2020Volume 172, Issue 11Page: 775-776KeywordsConflicts of interestDisclosureRandomized trials ePublished: 2 June 2020 Issue Published: 2 June 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Use of artificial intelligence for analyzing emotion vs patient global impression of change of melanoma treatments.
Authors: Ashley Su, Léonie Dupuis, Jeremy Jueng, Anuj Kunadia, Ian Brooks, Ritika Sinha, Fahad Siddiqui, Brittany Maner, Tanner Harding, Vernon Burton, Robert Dellavalle, Jennifer Seyffert, James A. Solomon
Journal: Journal of Clinical Oncology (2020)

e24177 Background: The link between melanoma patients’ emotions and their impressions of treatments response are poorly understood. With the rise of social media, patients use online platforms to communicate their concerns related to melanoma treatments. In this study, we utilize real-world data collected from social media with search terms focused on treatment-specific Patients’ Global Impression of Change (PGIC) compared with their emotions. We aim to identify and focus melanoma patient perspective trends to improve patient-centered care. Methods: Social media data mining of search terms were extracted from millions of publicly available interactions on Twitter and other online platforms from May/2008 to January/2020 using Crimson Hexagon (database of real-time social media posts). Results: For chemotherapy posts, the top three emotions by volume were negative alongside negative PGIC “worse” (Worse/Sadness 700, Worse/Fear 596, Worse/Disgust 403, and “decline” (Decline/Sadness 262, Decline/Fear 186, Decline/Disgust 57). Interestingly, Sadness, Fear, and Disgust were as prevalent alongside positive PGIC “well” and “cured” (Well/Sadness 3577, Well/Fear 2545, and Well/Disgust 1770; Cured/Sadness 518, Cured/Disgust 275, and Cured/Fear 167). For Keytruda treatment posts, emotions in negative PGIC “worse” were (Worse/Fear 117, Worse/Anger 68, Worse/Sadness 6). In positive PGIC “well”, results were (Well/Fear 880, Well/Sadness 366, Well/Anger 186). Further analysis will compare these emotional sentiments with a spectrum of PGIC terms and specific types of melanoma treatments. Conclusions: To our knowledge, this is the first investigation of online patient melanoma treatments associated with PGIC terms. The findings indicate a trend of negative emotions even when patients have reported wellness or being cured by treatment. While treatments may be effective, patients are not necessarily satisfied. Correlating changes in emotions with perceived changes in disease severity can provide insight into patient perspectives, which has implications in translating clinical response and a need for continued emotional support in patients with treatment response.
Towards elimination of childhood and adolescent tuberculosis in the Netherlands: an epidemiological time-series analysis of national surveillance data
Authors: Fajri Gafar, Taichi Ochi, Natasha van't Boveneind-Vrubleuskaya, Onno W. Akkerman, Connie Erkens, Susan van den Hof, Tjip S. van der Werf, Jan-Willem C. Alffenaar, Bob Wilffert
Journal: European Respiratory Journal (2020)

Background Tuberculosis (TB) in children and adolescents is a sentinel event for ongoing transmission. In the Netherlands, epidemiological characteristics of childhood and adolescent TB have not been fully evaluated. Therefore, we aimed to assess TB epidemiology within this population to provide guidance for TB elimination. Methods A retrospective time-series analysis using national surveillance data from 1993–2018 was performed in children (aged &lt;15 years) and adolescents (aged 15–19 years) with TB. Poisson regression models offset with log-population size were used to estimate notification rates and rate ratios. Trends in notification rates were estimated using average annual percentage changes (AAPC) based on the segmented linear regression analysis. Results Among 3899 children and adolescents with TB notified during 1993–2018, 2418 (62%) were foreign-born (725 (41.3%) out of 1755 children and 1693 (78.9%) out of 2144 adolescents). The overall notification rate in children was 2.3 per 100 000 person-years, declining steadily during the study period (AAPC −10.9%, 95% CI −12.6–−9.1). In adolescents, the overall notification rate was 8.4 per 100 000 person-years, strongly increasing during 1993–2001 and 2012–2018. Compared to Dutch-born children and adolescents, substantially higher notification rates were observed among African-born children and adolescents (116.8 and 316.6 per 100 000 person-years, respectively). Additionally, an increasing trend was observed in African-born adolescents (AAPC 18.5%, 95% CI 11.9–25.5). Among the foreign-born population, those from countries in the horn of Africa contributed most to the TB caseload. Conclusion TB notification rate among children was low and constantly declining across different demographic groups. However, heterogeneities were shown in adolescents, with an increasing trend in the foreign-born, particularly those from Africa.
Diabetic foot
Authors: Mishra Satish Chandra, Chhatbar Kunal C, Kashikar Aditi, Mehndiratta Abha, 李佳正, 吴巍巍
Journal: BMJ (2018)

有近6%的糖尿病患者发生足部病变1，包括足部感染、溃疡、组织坏死2。足部病变会损害糖尿病患者的生活质量，降低社会参与度，破坏生活能力3。0.03%~1.5%的糖尿病足患者需要截肢4。通过良好的足部医疗和筛查高危糖尿病足的危险因素，可以预防大部分的糖尿病足溃疡5。本文对在初级医疗中如何预防和早期管理糖尿病足进行了知识更新。
小疏忽引起的大问题
Authors: 曾昭耆
Journal: BMJ (2006)

多年前,一个60多岁的男性糖尿病患者,因发生重度酮症酸中毒住院,经积极抢救后逐渐好转,即将出院.在初期的治疗过程中,为便于及时给药,主管医生通过右侧股静脉插入了中心静脉导管.随着病情好转,这根导管本已不必保留.但主管医生认为,导管至今仍通畅,无感染,故打算干脆等到患者出院当天再拔除,以备万一需临时静脉给药时不必另行穿刺.应该说,他的这种想法是合理的。
Novel approaches in marginal zone lymphoma: Systematic review.
Authors: Seren Durer, Ceren Durer, Gilles Jad Hoilat, Rashad Khan, David B. Duggan, Hani M. Babiker, Faiz Anwer
Journal: Journal of Clinical Oncology (2020)

e20089 Background: Marginal zone lymphoma represents no more than 17% of NHLs and there is no standard of care. We reviewed the efficacy of novel drugs with main focus on ORR and PFS/OS (when available). Methods: Literature search was performed based on PRISMA guidelines in PubMed, Cochrane, EMBASE, Clinicaltrials.gov. Studies which did not give separate results for MZL were excluded. Results: 23 trials (n = 1491 patients) were included. 57% were refractory to previous line of therapy. 9 studies were conducted specifically in MZL (n = 440). The most common intervention was Rituximab and its combinations. PFS and OS were inconsistently reported. 1. Monotherapy in untreated MZL: In a phase III study, ORR was reported at 82.8% vs 81.3% with PFS of 75% vs 78% at 3 years in Obinutuzumab vs Rituximab. In Phase II Ibritumumumab tiuxetan showed 100% ORR in 11 patients with 5-year PFS of 82%. Most common grade 3-4 AE were hematological. Lenalidomide was studied in 18 EMZL patients, with 60% being untreated. In this study, ORR was reported at 61% with CR 33%. 2. Combination therapy in untreated MZL: Lenalidomide+Rituximab showed 93% ORR and median PFS 59.8 months with manageable toxicities. Ibrutinib in combination with Rituximab and Lenalidomide produced ORR of 90% with CR 60%. The addition of Bendamustine to Rituximab showed ORR and CR of 91% and 73% with 3-year PFS of 93% in a study of only SMZL (n = 56). 3. Monotherapy in R/R MZL: Ibrutinib demonstrated ORR of 50%, 54% and 41% in EMZL, SMZL and NMZL, respectively with median PFS of 14.2 months. Less hematologic toxicity was seen in MZL patients receiving Ibrutinib monotherapy compared to other regimens. In 30 patients receiving Everolimus, ORR was reported at 25%. Bortezomib has significant activity in EMZL with ORR of 48%. PI3Kδ inhibitors Idelalisib, Copanlisib and Duvelisib showed clinical activity. Umbrelisib and Ofatumumab demonstrated ORR &gt; 50%. Vorinostat demonstrated an ORR of 22%. 4. Combination therapy in R/R MZL: Rituximab+Lenalidomide had a higher ORR (39.4 vs. 14.1%) and higher PFS (58 vs. 36% at 2-year) compared to Rituximab monotherapy. Combination of Tirabrutinib and Entospletinib showed 20% ORR in a small group of MZL patients. Addition of Idelalisib to Tirabrutinib demonstrated ORR 40%. Ibrutinib and Venetoclax combination demonstrated ORR &gt; 50%. Ublituximab and Umbralisib showed clinical activity. Conclusions: With expanding armamentarium of targeted agents, our review has demonstrated positive results especially in terms of ORR in patients with MZL. Further studies are required to explore the role of these drugs and their impact on survival.
Adipocytes in hematopoiesis and acute leukemia: friends, enemies, or innocent bystanders?
Authors: Julia Zinngrebe, Klaus-Michael Debatin, Pamela Fischer-Posovszky
Journal: Leukemia (2020)

The bone marrow is home to well-balanced normal hematopoiesis, but also the stage of leukemia's crime. Marrow adipose tissue (MAT) is a unique and versatile component of the bone marrow niche. While the importance of MAT for bone health has long been recognized, its complex role in hematopoiesis has only recently gained attention. In this review article we summarize recent conceptual advances in the field of MAT research and how these developments impact our understanding of MAT regulation of hematopoiesis. Elucidating routes of interaction and regulation between MAT and cells of the hematopoietic system are essential to pinpoint vulnerable processes resulting in malignant transformation. The concept of white adipose tissue contributing to cancer development and progression on the cellular, metabolic, and systemic level is generally accepted. The role of MAT in malignant hematopoiesis, however, is controversial. MAT is very sensitive to changes in the patient's metabolic status hampering a clear definition of its role in different clinical situations. Here, we discuss future directions for leukemia research in the context of metabolism-induced modifications of MAT and other adipose tissues and how this might impact on leukemia cell survival, proliferation, and antileukemic therapy.
Efficacy and safety of different drugs by balloon catheter injection for no-reflow following percutaneous coronary intervention
Authors: Yuping Wang, Haibin Zhang, Zhenghai Zhang
Journal: BMJ (2019)

Objective
To evaluate the efficacy and safety of different drugs injected via balloon catheter for no-reflow after percutaneous coronary intervention (PCI) in patients with ST segment elevation myocardial infarction (STEMI).


Methods
From January 2016 to December 2017, 1 280 patients with STEMI were treated in Department of Cardiology, Beijing Luhe Hospital. All patients were underwent PCI and stent implantation in related infarct vessels (IRA). Among 1 280 patients no-reflow occurred in 164 cases (12.81%) during the procedure. No-reflow patients were divided into three study groups according to the order of consultation, who were given verapamil (verapamil group,55 cases),tirofiban (tirofiban group, 55 cases) or nitroglycerin (nitroglycerin group, 54 cases) by injection through balloon catheter. Coronary blood flow recovery (TIMI grading),myocardial perfusion level TMP grading (TMPG),average dose of drugs (mg) and adverse drug reactions (ADR) were compared among the three groups. Left ventricular ejection fraction (LVEF) and left ventricular end diastolic volume (LVEDV) were evaluated by echocardiography 7 and 30 d after operation. The incidence of major adverse cardiovascular events (MACE) was followed up.


Results
TIMI-3 ratio in verapamil, tirofiban and nitroglycerin groups was 89.90% (49/55), 91.82% (45/55) and 61.11% (33/54), respectively (Hc=13.920, P 0.05). There was no significant difference in LVEF and LVEDV among three groups on the d7 after operation (all P>0.05). The improvement of LVEF and LVEDV was more significant in verapamil group on d30 after operation (all P 0.05).


Conclusion
Verapamil can be injected throμgh balloon catheter to restore coronary blood flow rapidly, effectively and safely,and improve left ventricular function in STEMI patients with no-reflux during PCI.


Key words: 
Myocardial infarction; No-reflow phenomenon; Percutaneous coronary intervention; Vera pammy