tbuckley/cabot-search huggingface dataset:
From sequential to combination and personalised therapy in lupus nephritis: moving towards a paradigm shift?
Authors: Ioannis Parodis, Frederic A Houssiau
Journal: Annals of the Rheumatic Diseases (2021)

The current treatment paradigm in lupus nephritis consists of an initial phase aimed at inducing remission and a subsequent remission maintenance phase. With this so-called sequential treatment approach, complete renal response is achieved in a disappointing proportion of 20–30% of the patients within 6–12 months, and 5–20% develop end-stage kidney disease within 10 years. Treat-to-target approaches are detained owing to uncertainty as to whether the target should be determined based on clinical, histopathological, or immunopathological features. Until reliable non-invasive biomarkers exist, tissue-based evaluation remains the gold standard, necessitating repeat kidney biopsies for treatment evaluation and therapeutic decision-making. In this viewpoint, we discuss the pros and cons of voclosporin and belimumab as add-on agents to standard therapy, the first drugs to be licenced for lupus nephritis after recent successful randomised phase III clinical trials. We also discuss the prospect of obinutuzumab and anifrolumab, also on top of standard immunosuppression, currently tested in phase III trials after initial auspicious signals. Undoubtably, the treatment landscape in lupus nephritis is changing, with combination treatment regimens challenging the sequential concept. Meanwhile, the enrichment of the treatment armamentarium shifts the need from lack of therapies to the challenge of how to select the right treatment for the right patient. This has to be addressed in biomarker surveys along with tissue-level mapping of inflammatory phenotypes, which will ultimately lead to person-centred therapeutic approaches. After many years of trial failures, we may now anticipate a heartening future for patients with lupus nephritis.
Suicide reduction in Canada during the COVID-19 pandemic: lessons informing national prevention strategies for suicide reduction
Authors: Roger S McIntyre, Leanna MW Lui, Joshua D Rosenblat, Roger Ho, Hartej Gill, Rodrigo B Mansur, Kayla Teopiz, Yuhua Liao, Ciyong Lu, Mehala Subramaniapillai, Flora Nasri, Yena Lee
Journal: Journal of the Royal Society of Medicine (2021)

Objective The objective of this research was to evaluate the impact of federal, public health and social support programs on national suicide rates in Canada. Design Cross-sectional study. Setting Canadian National Database (i.e., Statistics Canada) and Statista. Participants Population-level data, and economic and consumer market data. Main Outcome Measures Suicide mortality data, population data and unemployment data were obtained from available statistical databases (e.g. Statistics Canada). We quantified suicide rate by dividing the total number of suicide deaths by the national population expressed as a rate per 100,000 population. Results Overall suicide mortality rate decreased in Canada from 10.82 deaths per 100,000 in the March 2019 - February 2020 period to 7.34 per 100,000 (i.e. absolute difference of 1300 deaths) in the March 2020 - February 2021 period. The overall Canadian unemployment rate changed from an average monthly rate of 5.7% in 2019 to 9.5% in 2020. Conclusion Our results indicate that for the first post-pandemic interval evaluated (i.e., March 2020 - February 2021), suicide rates in Canada decreased against a background of extraordinary public health measures intended to mitigate community spread of COVID-19. An externality of public health measures was a significant rise in national unemployment rates in population measures of distress. Our results suggest that government interventions that broadly aim to reduce measures of insecurity (i.e., economic, housing, health), and timely psychiatric services, should be prioritised as part of a national suicide reduction strategy, not only during but after termination of the COVID-19 pandemic.
Antibacterial Zeolite Imidazole Frameworks with Manganese Doping for Immunomodulation to Accelerate Infected Wound Healing
Authors: Yao Wan, Jiao Fang, Yu Wang, Jiao Sun, Yue Sun, Xiaolin Sun, Manlin Qi, Wen Li, Chunyan Li, Yanmin Zhou, Lin Xu, Biao Dong, Lin Wang
Journal: Advanced Healthcare Materials (2021)

Numerous nanomedicines currently emerge to reduce the dramatic threat in antibiotics resistance for antibacterial application against severe bacterial infections, while it is restricted by over-reacted immune response to pathogenic bacteria. Herein, enzymatic activity is introduced into the zeolitic imidazolate framework-8 (ZIF-8) to achieve sterilization by releasing Zn ions, as well as inflammation regulation through the variable valence of Mn ions that are uniformly doped into its framework. Within this simple metal organic framework (MOF) structure design, Mn-ZIF-8 possesses the co-existence of Mn2+ /Mn4+ to endow the nanocomposite with the anti-inflammatory capabilities, which can be adjusted through the redox environment. The enzymatic activity of Mn ions and superiority of pore structure of ZIF-8 are effectively combined to realize the substrate selection via reactant molecular size and high-efficiency internal catalytic performance. By such design, this nanocomposite would not only exhibit an excellent antibacterial performance against pathogenic bacteria, but also reshape the inflammatory immunity by regulating macrophage polarization to suppress over-reacted inflammation, leading to a favorably therapeutic efficiency on bacteria-infected wound healing in animal models. Taken together, this nanoplatform provides effective approach for accelerating infected wound healing via bacteria killing and inflammation modulation, and may be extended for the therapy of other severe bacteria-induced infections.
The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria
Authors: Torsten Zuberbier, Amir Hamzah Abdul Latiff, Mohamed Abuzakouk, Susan Aquilina, Riccardo Asero, Diane Baker, Barbara Ballmer‐Weber, Christine Bangert, Moshe Ben‐Shoshan, Jonathan A. Bernstein, Carsten Bindslev‐Jensen, Knut Brockow, Zenon Brzoza, Herberto Jose Chong Neto, Martin K. Church, Paulo R. Criado, Inna V. Danilycheva, Corinna Dressler, Luis Felipe Ensina, Luz Fonacier, Matthew Gaskins, Krisztian Gáspár, Aslı Gelincik, Ana Giménez‐Arnau, Kiran Godse, Margarida Gonçalo, Clive Grattan, Martine Grosber, Eckard Hamelmann, Jacques Hébert, Michihiro Hide, Allen Kaplan, Alexander Kapp, Aharon Kessel, Emek Kocatürk, Kanokvalai Kulthanan, Désirée Larenas‐Linnemann, Antti Lauerma, Tabi A. Leslie, Markus Magerl, Michael Makris, Raisa Y. Meshkova, Martin Metz, Daniel Micallef, Charlotte G. Mortz, Alexander Nast, Hanneke Oude‐Elberink, Ruby Pawankar, Paolo D. Pigatto, Hector Ratti Sisa, María Isabel Rojo Gutiérrez, Sarbjit S. Saini, Peter Schmid‐Grendelmeier, Bulent E. Sekerel, Frank Siebenhaar, Hanna Siiskonen, Angele Soria, Petra Staubach‐Renz, Luca Stingeni, Gordon Sussman, Andrea Szegedi, Simon Francis Thomsen, Zahava Vadasz, Christian Vestergaard, Bettina Wedi, Zuotao Zhao, Marcus Maurer
Journal: Allergy (2021)

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
Impact of multidisciplinary tumor board (MTB) discussion on the outcome of patients with liver-limited metastasis from colorectal cancer (LMCRC).
Authors: Paula Tavares Guimarães, Felipe José Fernández Coimbra, Celso Lopes Mello, Tiago Felismino
Journal: Journal of Clinical Oncology (2021)

50 Background: MTB is a valuable tool in complex cases, since they involve different medical fields aiming for a more comprehensive decision-making process. Our aims are to describe MTB decisions in complex LMCRC, to analyze decisions compliance and evaluate outcomes. Methods: This is a retrospective analysis of medical records of patients diagnosed with liver metastasis of colorectal carcinoma (LMCRC) discussed at a single center, weekly-basis MTB from January 2019 to December 2020. Descriptive statistics was used for demographic and treatment characteristics and adhesion to MTB decisions. Survival was estimated by Kaplan-Meier method and log-rank tests. Results: Out of 1033 cases discussed at MTB, 63 met the inclusion criteria. Median age was 56.5 years (range 32 – 81), 61.9% were male, ECOG was 0-1 in 96.8%. Regarding primary tumor sidedness: 81% and 19% were left and right, respectively. Synchronous metastasis was present in 69.8% and wild-type RAS was found in 52.4% and MSI-H in 4.8%. At time of MTB, 68.3% and 4.8% had realized a first or second-line chemotherapy (CT) respectively. No previous therapy was described in 19% and 7.9% had received adjuvant CT. Previous hepatic resections occurred in 20.6%. After MTB, liver resection was recommended for 44.5%. Preoperative CT followed by one or two-stage surgery for 23.8%. Non-surgical treatments were offered for 17.5% and palliative CT for 14.3%. Decisions from the MTB were implemented in 93.6%. Reason for not performing (N = 4) were: one for disease progression, one for bureaucratic restriction and two for other reasons. Median follow-up time was 17.2m. At date of analysis, 31 patients (49.2%) had relapsed or progressed and 8 had died. Restricting for patients who underwent MTB decision (N = 59), mPFS was 14.71m. In resected cases (N = 40), who were discussed at the onset of liver metastasis diagnosis (without CT in the metastatic setting) had mPFS not reached, while who were discussed after first or second-line had mPFS of 9.39m (p 0.002). R0 resections were reached in 92.5%. Evaluating the 30-day postoperative mortality, there was one death. mPFS for palliative CT was 6.83m. Conclusions: In our analysis the adherence to MTB recommendation was high (above 90%) and patients selected for surgery presented a prolonged PFS. Our data suggest that selection of patients for liver metastasis resection in a MTB discussion should occur early in the course of treatment.
Convalescent plasma for SARS-CoV-2 infection: win or learn
Authors: Enric Contreras-Barbeta, Anna Millan, Jordi Rello
Journal: European Respiratory Journal (2021)

At the end of the 19th century, Emil von Behring (figure 1) demonstrated that serum from horses infected with diphtheria or tetanus was useful in treating people affected by these diseases, inaugurating passive immunisation as a new therapeutic strategy. He received the Nobel Prize in Physiology or Medicine in 1901. This finding opened the door to the use of plasma from convalescent patients to treat infectious diseases; and throughout history, convalescent plasma has been used to treat many diseases, such as Spanish influenza, poliomyelitis, Korean haemorrhagic fever and, more recently, Ebola virus disease and influenza A (influenza H1N1 virus). Current evidence does not support the use of convalescent plasma in the standard therapy for COVID-19 <https://bit.ly/3DGyz6t>
PL02.4.A Chromosome 1p19q codeletion frequency, but not survival, varies according to the IDH mutation subtypes: analysis of 1050 IDH-mutated diffuse gliomas
Authors: A Picca, G Berzero, A Di Stefano, N Trabelsi, F Bielle, M Sanson
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND recurring hotspot mutations in isocitrate dehydrogenase (IDH) 1 enzymes, and to a lesser extent IDH2, are the main oncogenic alteration in most of lower-grade diffuse gliomas and a subset of grade 4 gliomas. Although most commonly represented by the IDH1R132H mutation, non-canonical IDH1/2-nonR132H mutations are present in about 10% of cases. As the neomorphic enzymatic activity can vary depending on the type of the hotspot mutation, a different biological behaviour may be inferred. Nevertheless, the prognostic significance of the different IDH1/2 mutations remains a matter of debate. MATERIAL AND METHODS we queried the OncoNeuroTek tumor bank (Pitié-Salpêtrière Hospital, Paris) to identify all registered cases of IDH-mutated diffuse gliomas. Most relevant clinical and molecular data were collected. RESULTS We identified 1050 IDH mutated diffuse gliomas (481 grade 2 [46%], 459 grade 3 [44%], and 110 grade 4 [10%]), of which 1007 (96%) were IDH1 mutated (934 IDH1R132H [89%] and 73 IDH-nonR132H [7%]) and 43 (4%) were IDH2 mutated (24 IDH2R172K [2%] and 19 IDH2-nonR172K [2%]). The chromosomes 1p/19q codeletion was more frequent in IDH2-mutated tumors (25/42 [60%] versus 350/918 [38%] in IDH1-mutated cases, p=0.005). Nevertheless, only IDH2R172K mutation was associated with the codeletion (18/24 [75%], versus 7/18 [39%] in IDH2-nonR172K-mutated tumors, p=0.02). IDH1-nonR132H tumors showed the lowest rate of 1p/19q codeletion (9/69 [13%], versus 341/849 [40%] in IDH1R132H-mutated cases, p&amp;lt;0.001). At the time of observation, 536 patients were deceased (51%), with a median overall survival (OS) of 115 months (mo., 95% CI 108–125 mo.). Median follow up for censored patients was 77 mo. Codeleted patients had a significantly longer OS compared to non-codeleted ones (179 vs. 96 mo., p&amp;lt;0.001). No significant differences in survival were seen when stratifying according to IDH mutation type (115 mo. for IDH1R132H vs. 136 mo. for IDH1-nonR132H vs. 112 mo. for IDH2R172K vs. 150 mo. for IDH2-nonR172K, p=0.8). No differences were seen when restricting the analysis to codeleted or not-codeleted patients only, respectively. In a multivariate analysis including the main prognostic factors (age, sex, preoperative performance status, tumor grade, surgical resection, midline location, 1p/19q codeletion, and p16 homozygous deletion), no survival difference was associated with any of the IDH mutation subtype. CONCLUSION although significantly different rates of 1p/19q codeletion were seen according to the four main IDH mutation subgroups, these groups does not associate with different survival profiles in our cohort.
Further Considerations on the Association Between Flavored Tobacco Legislation and High School Student Smoking Rates
Authors: Eric C. Leas
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Effect of disease progression on the podocyte cell cycle in Alport Syndrome
Authors: Camille Nicolas Frank, Xiaogang Hou, Astgik Petrosyan, Valentina Villani, Rui Zhao, Joshua R. Hansen, Geremy Clair, Fadi Salem, Roger E. De Filippo, Paolo Cravedi, Kevin V. Lemley, Laura Perin
Journal: Kidney International (2021)

Progression of glomerulosclerosis is associated with loss of podocytes with subsequent glomerular tuft instability. It is thought that a diminished number of podocytes may be able to preserve tuft stability through cell hypertrophy associated with cell cycle reentry. At the same time, reentry into the cell cycle risks podocyte detachment if podocytes cross the G1/S checkpoint and undergo abortive cytokinesis. In order to study cell cycle dynamics during chronic kidney disease (CKD) development, we used a FUCCI model (fluorescence ubiquitination-based cell cycle indicator) of mice with X-linked Alport Syndrome. This model exhibits progressive CKD and expresses fluorescent reporters of cell cycle stage exclusively in podocytes. With the development of CKD, an increasing fraction of podocytes in vivo were found to be in G1 or later cell cycle stages. Podocytes in G1 and G2 were hypertrophic. Heterozygous female mice, with milder manifestations of CKD, showed G1 fraction numbers intermediate between wild-type and male Alport mice. Proteomic analysis of podocytes in different cell cycle phases showed differences in cytoskeleton reorganization and metabolic processes between G0 and G1 in disease. Additionally, in vitro experiments confirmed that damaged podocytes reentered the cell cycle comparable to podocytes in vivo. Importantly, we confirmed the upregulation of PDlim2, a highly expressed protein in podocytes in G1, in a patient with Alport Syndrome, confirming our proteomics data in the human setting. Thus, our data showed that in the Alport model of progressive CKD, podocyte cell cycle distribution is altered, suggesting that cell cycle manipulation approaches may have a role in the treatment of various progressive glomerular diseases characterized by podocytopenia.
Re: Guohua Zeng, Chao Cai, Xianzhong Duan, et al. Mini Percutaneous Nephrolithotomy Is a Noninferior Modality to Standard Percutaneous Nephrolithotomy for the Management of 20–40 mm Renal Calculi: A Multicenter Randomized Controlled Trial. Eur Urol 2021;80:114–21
Authors: Xiaoshuai Gao, Guo Chen, Tao Jin
Journal: European Urology (2021)
Effect of C reactive protein point-of-care testing on antibiotic prescribing for lower respiratory tract infections in nursing home residents: cluster randomised controlled trial
Authors: Tjarda M Boere, Laura W van Buul, Rogier M Hopstaken, Maurits W van Tulder, Jos W M R Twisk, Theo J M Verheij, Cees M P M Hertogh
Journal: BMJ (2021)

Abstract Objective To evaluate whether C reactive protein point-of-care testing (CRP POCT) safely reduces antibiotic prescribing for lower respiratory tract infections in nursing home residents. Design Pragmatic, cluster randomised controlled trial. Setting The UPCARE study included 11 nursing home organisations in the Netherlands. Participants 84 physicians from 11 nursing home organisations included 241 participants with suspected lower respiratory tract infections from September 2018 to the end of March 2020. Interventions Nursing homes allocated to the intervention group had access to CRP POCT. The control group provided usual care without CRP POCT for patients with suspected lower respiratory tract infections. Main outcome measures The primary outcome measure was antibiotic prescribing at initial consultation. Secondary outcome measures were full recovery at three weeks, changes in antibiotic management and additional diagnostics during follow-up at one week and three weeks, and hospital admission and all cause mortality at any point (initial consultation, one week, or three weeks). Results Antibiotics were prescribed at initial consultation for 84 (53.5%) patients in the intervention group and 65 (82.3%) in the control group. Patients in the intervention group had 4.93 higher odds (95% confidence interval 1.91 to 12.73) of not being prescribed antibiotics at initial consultation compared with the control group, irrespective of treating physician and baseline characteristics. The between group difference in antibiotic prescribing at any point from initial consultation to follow-up was 23.6%. Differences in secondary outcomes between the intervention and control groups were 4.4% in full recovery rates at three weeks (86.4% v 90.8%), 2.2% in all cause mortality rates (3.5% v 1.3%), and 0.7% in hospital admission rates (7.2% v 6.5%). The odds of full recovery at three weeks, and the odds of mortality and hospital admission at any point did not significantly differ between groups. Conclusions CRP POCT for suspected lower respiratory tract infection safely reduced antibiotic prescribing compared with usual care in nursing home residents. The findings suggest that implementing CRP POCT in nursing homes might contribute to reduced antibiotic use in this setting and help to combat antibiotic resistance. Trial registration Netherlands Trial Register NL5054
Validating a nodal regression system for gastric cancer: An ancillary cohort study of the GASTRODOC trial
Authors: Luca Saragoni, Leonardo Solaini, Daniele Marrelli, Maria Raffaella Ambrosio, Maria Bencivenga, Anna Tomezzoli, Carlo Milandri, Valentina Terrinazzi, Gian Luca Baiocchi, Carla Baronchelli, Flavia Foca, Giorgio Ercolani, Paolo Morgagni
Journal: International Journal of Surgery (2021)