Publications by authors named "Paul Wallace"

226 Publications

Phase I Clinical Trial of Combination Propranolol and Pembrolizumab in Locally Advanced and Metastatic Melanoma: Safety, Tolerability, and Preliminary Evidence of Antitumor Activity.

Clin Cancer Res 2021 Jan 30;27(1):87-95. Epub 2020 Oct 30.

Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

Purpose: Increased β-adrenergic receptor (β-AR) signaling has been shown to promote the creation of an immunosuppressive tumor microenvironment (TME). Preclinical studies have shown that abrogation of this signaling pathway, particularly β2-AR, provides a more favorable TME that enhances the activity of anti-PD-1 checkpoint inhibitors. We hypothesize that blocking stress-related immunosuppressive pathways would improve tumor response to immune checkpoint inhibitors in patients. Here, we report the results of dose escalation of a nonselective β-blocker (propranolol) with pembrolizumab in patients with metastatic melanoma.

Patients And Methods: A 3 + 3 dose escalation study for propranolol twice a day with pembrolizumab (200 mg every 3 weeks) was completed. The primary objective was to determine the recommended phase II dose (RP2D). Additional objectives included safety, antitumor activity, and biomarker analyses. Responders were defined as patients with complete or partial response per immune-modified RECIST at 6 months.

Results: Nine patients with metastatic melanoma received increasing doses of propranolol in cohorts of 10, 20, and 30 mg twice a day. No dose-limiting toxicities were observed. Most common treatment-related adverse events (TRAEs) were rash, fatigue, and vitiligo, observed in 44% patients. One patient developed two grade ≥3 TRAEs. Objective response rate was 78%. While no significant changes in treatment-associated biomarkers were observed, an increase in IFNγ and a decrease in IL6 was noted in responders.

Conclusions: Combination of propranolol with pembrolizumab in treatment-naïve metastatic melanoma is safe and shows very promising activity. Propranolol 30 mg twice a day was selected as RP2D in addition to pembrolizumab based on safety, tolerability, and preliminary antitumor activity.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-2381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785669PMC
January 2021

CD319 (SLAMF7) an alternative marker for detecting plasma cells in the presence of daratumumab or elotuzumab.

Cytometry B Clin Cytom 2020 Oct 5. Epub 2020 Oct 5.

Department of Flow and Image Cytometry, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.

Background: Daratumumab is an anti-CD38 immunotherapeutic drug that has increasingly been used to treat patients with heavily pre-treated and relapsed/refractory multiple myeloma. In so doing, the detection of CD38 antigen on plasma cells by flow cytometry is impeded. We hypothesized that alternative markers can be used in place or in addition to CD38 when detecting plasma cells post-treated with daratumumab.

Methods: A total of 16 alternative markers were tested using 22 bone marrow aspirates from patients with plasma cell neoplasm. The ability of selected markers to discern plasma cells from other hematopoietic cells were evaluated. The stability of tested markers when stored at 4 or 25°C after T = 0, 24, 48, and 72 h was also established. Finally, selected markers were incorporated into a panel used for monitoring multiple myeloma measurable residual disease to test their utility to identify plasma cells in the presence of daratumumab and/or elotuzumab (anti-CD319) drugs.

Results: Out of the 16 tested markers, CD319, CD54, CD229, CD317, and p63 were expressed by >90% of the plasma cells. Only CD319, CD54, and CD229 achieved 100% detection sensitivity. Further analysis showed that CD319 was better than CD229 and CD54 at resolving plasma cells from background hematopoietic cells, with CD54 being the worst (resolution metric, mean ± SD: CD319 [2.04 ± 0.86]; CD229 [1.47 ± 0.45]; and CD54 [1.22 ± 0.60]). CD229 was expressed by >90% of T lymphocytes, whereas CD319 was expressed preferentially by the CD8+ T cells and less frequently in CD4+ T cells. Additionally, CD229 was found on >60% of B and NK cells, as well as minor subsets of monocytes and granulocytes. CD319 was expressed on most NK cells and a minor subset of B cells, granulocytes, and monocytes. Even though CD229 and CD319 were expressed by different leukocyte subsets, their expression levels were highest on plasma cells. The expression of CD138 on plasma cells was significantly lower after storage at 4°C, while the expression levels of CD38, CD229, and CD319 remained stable at 4 or 25°C. Using limiting dilution experiments, the treatment of cells with daratumumab severely impeded the detection of CD38 antigen on plasma cells, whereas elotuzumab treatment did not block detection of CD319 on plasma cells.

Conclusions: CD319 is a suitable alternative to CD38 for identifying plasma cells. Our results showed that a panel used for monitoring multiple myeloma measurable residual disease could be modified by using CD319 alone or in combination with CD38 to detect PCs in daratumumab or elotuzumab treated patients.
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http://dx.doi.org/10.1002/cyto.b.21961DOI Listing
October 2020

Circulating CD14 HLA-DR monocytic cells as a biomarker for epithelial ovarian cancer progression.

Am J Reprod Immunol 2021 Mar 21;85(3):e13343. Epub 2020 Sep 21.

Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

Problem: Previous studies identified circulating CD14 HLA-DR monocytic cells as an immune suppressive subset in solid malignancies, such as prostate, renal cell carcinoma, and pancreatic cancer. Such monocytic cells have been implicated not only in tumour progression but also as a potential barrier for immunotherapy. This study examined the relationship between the frequency of circulating monocytic cells and epithelial ovarian cancer (EOC) progression pre- and post-frontline chemotherapy, defined by disease stage, which is a leading prognostic factor for this malignancy.

Method Of Study: Incident cases of 236 women with EOC were recruited and comprehensive flow cytometry was utilized to assess the frequency of peripheral blood CD33 CD11b HLA-DR CD14 CD15 monocytic cells, henceforth termed CD14 HLA-DR monocytic cells, prior to and after completion of frontline chemotherapy. Multivariable odds ratios (OR) were used to estimate the association between CD14 HLA-DR monocytic cell percentages and disease stage. Wilcoxon signed-rank tests evaluated changes in these monocytic cell levels pre- and post-chemotherapy in a patient subset (n = 70).

Results: Patients with elevated frequencies of circulating CD14 HLA-DR monocytic cells at diagnosis were at 3.33-fold greater odds of having advanced stage (III/IV) EOC (CI: 1.04-10.64), with a significant trend in increasing CD14 HLA-DR monocytic cell levels (P = .04). There was a 2.02% median decrease of these monocytic cells post-chemotherapy among a subset of patients with advanced stage disease (P < .0001).

Conclusion: These findings support the potential clinical relevance of CD14 HLA-DR monocytic cells in EOC for prognosis and may indicate a non-invasive biomarker to measure disease progression.
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http://dx.doi.org/10.1111/aji.13343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897210PMC
March 2021

Low-Level Cytomegalovirus Antigenemia Promotes Protective Cytomegalovirus Antigen-Specific T Cells after Allogeneic Hematopoietic Cell Transplantation.

Biol Blood Marrow Transplant 2020 11 25;26(11):2147-2154. Epub 2020 Jul 25.

Department of Medicine, Transplant and Cellular Therapy Program, Roswell Park, Buffalo, New York.

Previous studies have reported a beneficial effect from cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplantation (alloHCT) on immune reconstitution. We determined the CMV antigenemia level associated with increased CMV antigen-specific T cells (CASTs) at day +100 and decreased CMV reactivation after day +100. CMV reactivation and CASTs were measured with CMV antigenemia and CMV-specific major histocompatibility complex multimers. The analysis consisted of 775 CAST measurements obtained before and 30, 100, and 365 days post-alloHCT from 327 consecutive patients treated between 2008 and 2016. Detectable CASTs correlated with recipient (P < .0001) and donor (P < .0001) CMV seropositivity pre-alloHCT. CMV reactivation before day +100 was associated with a higher proportion of patients who achieved ≥3 CASTs/µL by day +100 (61% with versus 39% without reactivation, P < .001). In alloHCT recipients at high risk for CMV reactivation (RD) with a maximum of grade II acute graft-versus-host-disease, reactivating CMV before day +100 and achieving ≥3 versus <3 CASTs/µL at day +100 was associated with reduced CMV reactivation from day +100 to +365 (27% versus 62%, P = .04). This protective effect was observed with low-level but not high-level CMV reactivation (<5 versus ≥5/50,000 polymorphonuclear leukocytes + pp65, respectively). These findings suggest low-level CMV reactivation may be beneficial and that treatment may be delayed until progression. These findings will need validation in prospective clinical trials using CMV PCR and antigenemia assays.
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http://dx.doi.org/10.1016/j.bbmt.2020.07.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609607PMC
November 2020

International external quality assessment for SARS-CoV-2 molecular detection and survey on clinical laboratory preparedness during the COVID-19 pandemic, April/May 2020.

Euro Surveill 2020 07;25(27)

Details on these projects are noted in the Acknowledgements.

Laboratory preparedness with quality-assured diagnostic assays is essential for controlling the current coronavirus disease (COVID-19) outbreak. We conducted an external quality assessment study with inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) samples to support clinical laboratories with a proficiency testing option for molecular assays. To analyse SARS-CoV-2 testing performance, we used an online questionnaire developed for the European Union project RECOVER to assess molecular testing capacities in clinical diagnostic laboratories.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.27.2001223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364759PMC
July 2020

Blockade of p38 kinase impedes the mobilization of protumorigenic myeloid populations to impact breast cancer metastasis.

Int J Cancer 2020 Oct 28;147(8):2279-2292. Epub 2020 May 28.

Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.

Patients with metastatic breast cancer (MBC) have limited therapeutic options and novel treatments are critically needed. Prior research implicates tumor-induced mobilization of myeloid cell populations in metastatic progression, as well as being an unfavorable outcome in MBC; however, the underlying mechanisms for these relationships remain unknown. Here, we provide evidence for a novel mechanism by which p38 promotes metastasis. Using triple-negative breast cancer models, we showed that a selective inhibitor of p38 (p38i) significantly reduced tumor growth, angiogenesis, and lung metastasis. Importantly, p38i decreased the accumulation of myeloid populations, namely, myeloid-derived suppressor cells (MDSCs) and CD163 tumor-associated macrophages (TAMs). p38 controlled the expression of tumor-derived chemokines/cytokines that facilitated the recruitment of protumor myeloid populations. Depletion of MDSCs was accompanied by reduced TAM infiltration and phenocopied the antimetastatic effects of p38i. Reciprocally, p38i increased tumor infiltration by cytotoxic CD8 T cells. Furthermore, the CD163 /CD8 expression ratio inversely correlated with metastasis-free survival in breast cancer, suggesting that targeting p38 may improve clinical outcomes. Overall, our study highlights a previously unknown p38-driven pathway as a therapeutic target in MBC.
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http://dx.doi.org/10.1002/ijc.33050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484223PMC
October 2020

Barriers to learning and using point-of-care ultrasound: a survey of practicing internists in six North American institutions.

Ultrasound J 2020 Apr 19;12(1):19. Epub 2020 Apr 19.

Department of Medicine, Division of General Internal Medicine, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada.

Background: Point-of-care ultrasound (POCUS) is increasingly used in internal medicine, but a lack of trained faculty continues to limit the spread of POCUS education. Using a framework based on organizational change theories, this study sought to identify barriers and enablers for hospital-based practicing internists to learn and use POCUS in clinical practice.

Methods: We invited practicing internists at six North American institutions to participate in an electronic survey on their opinions regarding 39 barriers and enablers.

Results: Of the 342 participants invited, 170 participated (response rate 49.3%). The top barriers were lack of training (79%), lack of handheld ultrasound devices (78%), lack of direct supervision (65%), lack of time to perform POCUS during rounds (65%), and lack of quality assurance processes (53%). The majority of participants (55%) disagreed or strongly disagreed with the statement "My institution provides funding for POCUS training." In general, participants' attitudes towards POCUS were favourable, and future career opportunities and the potential for billing were not considered significant factors by our participants in the decision to learn or use POCUS.

Conclusions: This survey confirms the perceived importance of POCUS to practicing internists. To assist in closing faculty development gap, interventions should address training, supervision, quality assurance processes, availability of handheld devices, as well as dedicated time to perform POCUS during clinical care.
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http://dx.doi.org/10.1186/s13089-020-00167-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167384PMC
April 2020

Reply to: Using Point-of-Care Ultrasound on Home Visits.

J Am Geriatr Soc 2020 03 9;68(3):669. Epub 2020 Jan 9.

Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1111/jgs.16318DOI Listing
March 2020

Methodological considerations for the high sensitivity detection of multiple myeloma measurable residual disease.

Cytometry B Clin Cytom 2020 03 23;98(2):161-173. Epub 2019 Dec 23.

Department of Flow and Image Cytometry, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

Background: Recent advances in therapeutic interventions have dramatically improved complete response rates in patients with multiple myeloma (MM). The ability to identify residual myeloma cells (e.g., measurable residual disease [MRD]) can provide valuable information pertaining to patient's depth of response to therapy and risk of relapse. Multiparametric flow cytometry is an excellent technique to monitor MRD and has been demonstrated to correlate with patient outcome post-treatment. To achieve the high sensitivity (one abnormal cell in 10 -10 cells) required for MRD evaluation, millions of cells have to be acquired and conventional immunophenotyping protocols are unable to attain these numbers, indicating the needs for alternative flow cytometric staining procedures. A bulk, "Pre-lysis" method is the consensus approach for staining large number of cells, requires two red blood cell lysis steps, and can adversely affect epitope density. In this study, we tested the "Pooled-tube" and "Dextran Sedimentation" staining procedures and correlated them with the "Pre-lysis" method as potential alternative approaches.

Methods: A total of 22 bone marrow aspirates from patients with plasma cell (PC) dyscrasia were processed in parallel using the "Pre-lysis," "Pooled-tube," and "Dextran Sedimentation" techniques. Stain indices were calculated and compared to assess their impacts on staining performance for each antibody used in the consensus panel. The recovery of normal and abnormal PCs, mast cells, and B cell precursors was enumerated and compared after their counts were normalized using fluorescent beads. The limit of blank, limit of detection, and lower limit of quantification were established using serial dilution experiments.

Results: The staining performances of CD19 PECy7, CD27 BV510, CD81 APCH7, and CD138 BV421 were improved using the "Pooled-tube" method when compared to "Pre-lysis." "Pre-lysis" was better at resolving CD56 using clone C5.9 but our results demonstrated similar improvement can also be achieved by "Pooled-tube" when alternative CD56 PE clones were used. "Dextran sedimentation" yielded similar staining results when compared to "Pre-lysis" for all the markers analyzed. The "Pooled-tube" method, when normalized to "Pre-lysis," recovered higher numbers of total PCs (1.2 ± 0.2 times higher; p = .049), normal PCs (1.4 ± 0.26; p = .007), mast cells (1.46 ± 0.27; p = .003), and B cell precursors (1.42 ± 0.3; p = .011), but not abnormal PCs (1.09 ± 0.2; p = .352). There was no evidence that the recovery of cells was different between "Pre-lysis" versus "Dextran Sedimentation." All three flow cytometric assays achieved a minimum sensitivity of 10 and approached that of 10 for detecting rare events.

Conclusion: Both "Pooled-tube" and "Dextran Sedimentation" staining procedures were comparable to the "Pre-lysis" method and are suitable high sensitivity flow cytometric approaches that can be used to process bone marrow samples for MM MRD testing.
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http://dx.doi.org/10.1002/cyto.b.21862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7741435PMC
March 2020

MiSet RFC Standards: Defining a Universal Minimum Set of Standards Required for Reproducibility and Rigor in Research Flow Cytometry Experiments.

Cytometry A 2020 02 26;97(2):148-155. Epub 2019 Nov 26.

New York University School of Medicine, New York, New York.

Poor adherence to best practices, insufficient training, and pressure to produce data quickly may lead to publications of suboptimal biomedical research flow cytometry data, which contributes to the body of irreproducible research findings. In addition, documentation of compliance with best flow cytometry practices for submission, visualization, and publication of flow cytometry data is currently endorsed by very few scientific journals, which is particularly concerning as numerous peer-reviewed flow cytometry publications emphasize instrumentation, experimental design, and data analysis as important sources of variability. Guidelines and resources for adequate reporting, annotation and deposition of flow cytometry experiments are provided by MIFlowCyt and the FlowRepository database, and comprehensive expert recommendations covering principles and techniques of field-specific flow cytometry applications have been published. To facilitate the integration of quality-defining parameters into manuscript and grant submission and publication requirements across biomedical fields that rely on the use of flow-cytometry-based techniques, a single comprehensive yet easily and universally applicable document is needed. To produce such a list of gold-standard parameters that assess whether a research flow cytometry experiment has been planned, conducted, interpreted, and reported at the highest standard, a new initiative defining the minimum set of standards a robust and rigorous research flow experiment must fulfill (MiSet RFC Standards) was proposed at CYTO 2019. MiSet RFC Standards will integrate and simplify existing resources to provide a universal benchmark a flow cytometry experiment can easily be measured against. The goal of MiSET RFC Standards is its integration into peer-review and publication procedures through partnership with stakeholders, journals and publishers in biomedical and translational research. This article introduces the aims and anticipated timeline and discusses strategies for interdisciplinary consensus and implementation. A single-resource broadly applicable guideline will harmonize standards across different fields of biomedical research and lead to publication of more robust research findings. © 2019 International Society for Advancement of Cytometry.
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http://dx.doi.org/10.1002/cyto.a.23940DOI Listing
February 2020

Simultaneous Polychromatic Immunofluorescent Staining of Tissue Sections and Consecutive Imaging of up to Seven Parameters by Standard Confocal Microscopy.

Curr Protoc Cytom 2019 12;91(1):e64

Malaghan Institute of Medical Research, Wellington, New Zealand.

Confocal microscopy has been an important imaging tool for life scientists for over 20 years. Early techniques focused on indirect staining processes that involved staining with an unconjugated primary antibody, followed by incubation with a secondary fluorescent antibody that would reveal and amplify the signal of the primary antibody. With more and more directly conjugated fluorescent primary antibodies becoming commercially available, staining with multiple fluorescent primary antibodies is now more frequent. To date, staining with up to three primary antibodies and a nuclear dye is widely practiced. Here, we describe an important improvement to the standard polychromatic immunofluorescent staining protocol that allows the simultaneous detection of seven fluorescent parameters using a standard confocal laser scanning microscope with four laser lines and four photomultiplier tubes. By incorporating recently available tandem dyes that emit in the blue and violet regions of the visible light spectrum (Brilliant Blue and Brilliant Violet), we were able to differentiate several additional fluorochromes simultaneously. Due to the added complexity of 7-color immunofluorescent imaging, we developed a clear methodology to optimize antibody concentrations and simple guidelines on how to identify and correct non-specific signals. These are detailed in the following protocol. © 2019 by John Wiley & Sons, Inc. Basic Protocol: 7-Color immunofluorescent staining protocol using directly conjugated antibodies Support Protocol 1: Antibody titration protocol Support Protocol 2: Spillover optimization protocol.
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http://dx.doi.org/10.1002/cpcy.64DOI Listing
December 2019

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition).

Authors:
Andrea Cossarizza Hyun-Dong Chang Andreas Radbruch Andreas Acs Dieter Adam Sabine Adam-Klages William W Agace Nima Aghaeepour Mübeccel Akdis Matthieu Allez Larissa Nogueira Almeida Giorgia Alvisi Graham Anderson Immanuel Andrä Francesco Annunziato Achille Anselmo Petra Bacher Cosima T Baldari Sudipto Bari Vincenzo Barnaba Joana Barros-Martins Luca Battistini Wolfgang Bauer Sabine Baumgart Nicole Baumgarth Dirk Baumjohann Bianka Baying Mary Bebawy Burkhard Becher Wolfgang Beisker Vladimir Benes Rudi Beyaert Alfonso Blanco Dominic A Boardman Christian Bogdan Jessica G Borger Giovanna Borsellino Philip E Boulais Jolene A Bradford Dirk Brenner Ryan R Brinkman Anna E S Brooks Dirk H Busch Martin Büscher Timothy P Bushnell Federica Calzetti Garth Cameron Ilenia Cammarata Xuetao Cao Susanna L Cardell Stefano Casola Marco A Cassatella Andrea Cavani Antonio Celada Lucienne Chatenoud Pratip K Chattopadhyay Sue Chow Eleni Christakou Luka Čičin-Šain Mario Clerici Federico S Colombo Laura Cook Anne Cooke Andrea M Cooper Alexandra J Corbett Antonio Cosma Lorenzo Cosmi Pierre G Coulie Ana Cumano Ljiljana Cvetkovic Van Duc Dang Chantip Dang-Heine Martin S Davey Derek Davies Sara De Biasi Genny Del Zotto Gelo Victoriano Dela Cruz Michael Delacher Silvia Della Bella Paolo Dellabona Günnur Deniz Mark Dessing James P Di Santo Andreas Diefenbach Francesco Dieli Andreas Dolf Thomas Dörner Regine J Dress Diana Dudziak Michael Dustin Charles-Antoine Dutertre Friederike Ebner Sidonia B G Eckle Matthias Edinger Pascale Eede Götz R A Ehrhardt Marcus Eich Pablo Engel Britta Engelhardt Anna Erdei Charlotte Esser Bart Everts Maximilien Evrard Christine S Falk Todd A Fehniger Mar Felipo-Benavent Helen Ferry Markus Feuerer Andrew Filby Kata Filkor Simon Fillatreau Marie Follo Irmgard Förster John Foster Gemma A Foulds Britta Frehse Paul S Frenette Stefan Frischbutter Wolfgang Fritzsche David W Galbraith Anastasia Gangaev Natalio Garbi Brice Gaudilliere Ricardo T Gazzinelli Jens Geginat Wilhelm Gerner Nicholas A Gherardin Kamran Ghoreschi Lara Gibellini Florent Ginhoux Keisuke Goda Dale I Godfrey Christoph Goettlinger Jose M González-Navajas Carl S Goodyear Andrea Gori Jane L Grogan Daryl Grummitt Andreas Grützkau Claudia Haftmann Jonas Hahn Hamida Hammad Günter Hämmerling Leo Hansmann Goran Hansson Christopher M Harpur Susanne Hartmann Andrea Hauser Anja E Hauser David L Haviland David Hedley Daniela C Hernández Guadalupe Herrera Martin Herrmann Christoph Hess Thomas Höfer Petra Hoffmann Kristin Hogquist Tristan Holland Thomas Höllt Rikard Holmdahl Pleun Hombrink Jessica P Houston Bimba F Hoyer Bo Huang Fang-Ping Huang Johanna E Huber Jochen Huehn Michael Hundemer Christopher A Hunter William Y K Hwang Anna Iannone Florian Ingelfinger Sabine M Ivison Hans-Martin Jäck Peter K Jani Beatriz Jávega Stipan Jonjic Toralf Kaiser Tomas Kalina Thomas Kamradt Stefan H E Kaufmann Baerbel Keller Steven L C Ketelaars Ahad Khalilnezhad Srijit Khan Jan Kisielow Paul Klenerman Jasmin Knopf Hui-Fern Koay Katja Kobow Jay K Kolls Wan Ting Kong Manfred Kopf Thomas Korn Katharina Kriegsmann Hendy Kristyanto Thomas Kroneis Andreas Krueger Jenny Kühne Christian Kukat Désirée Kunkel Heike Kunze-Schumacher Tomohiro Kurosaki Christian Kurts Pia Kvistborg Immanuel Kwok Jonathan Landry Olivier Lantz Paola Lanuti Francesca LaRosa Agnès Lehuen Salomé LeibundGut-Landmann Michael D Leipold Leslie Y T Leung Megan K Levings Andreia C Lino Francesco Liotta Virginia Litwin Yanling Liu Hans-Gustaf Ljunggren Michael Lohoff Giovanna Lombardi Lilly Lopez Miguel López-Botet Amy E Lovett-Racke Erik Lubberts Herve Luche Burkhard Ludewig Enrico Lugli Sebastian Lunemann Holden T Maecker Laura Maggi Orla Maguire Florian Mair Kerstin H Mair Alberto Mantovani Rudolf A Manz Aaron J Marshall Alicia Martínez-Romero Glòria Martrus Ivana Marventano Wlodzimierz Maslinski Giuseppe Matarese Anna Vittoria Mattioli Christian Maueröder Alessio Mazzoni James McCluskey Mairi McGrath Helen M McGuire Iain B McInnes Henrik E Mei Fritz Melchers Susanne Melzer Dirk Mielenz Stephen D Miller Kingston H G Mills Hans Minderman Jenny Mjösberg Jonni Moore Barry Moran Lorenzo Moretta Tim R Mosmann Susann Müller Gabriele Multhoff Luis Enrique Muñoz Christian Münz Toshinori Nakayama Milena Nasi Katrin Neumann Lai Guan Ng Antonia Niedobitek Sussan Nourshargh Gabriel Núñez José-Enrique O'Connor Aaron Ochel Anna Oja Diana Ordonez Alberto Orfao Eva Orlowski-Oliver Wenjun Ouyang Annette Oxenius Raghavendra Palankar Isabel Panse Kovit Pattanapanyasat Malte Paulsen Dinko Pavlinic Livius Penter Pärt Peterson Christian Peth Jordi Petriz Federica Piancone Winfried F Pickl Silvia Piconese Marcello Pinti A Graham Pockley Malgorzata Justyna Podolska Zhiyong Poon Katharina Pracht Immo Prinz Carlo E M Pucillo Sally A Quataert Linda Quatrini Kylie M Quinn Helena Radbruch Tim R D J Radstake Susann Rahmig Hans-Peter Rahn Bartek Rajwa Gevitha Ravichandran Yotam Raz Jonathan A Rebhahn Diether Recktenwald Dorothea Reimer Caetano Reis e Sousa Ester B M Remmerswaal Lisa Richter Laura G Rico Andy Riddell Aja M Rieger J Paul Robinson Chiara Romagnani Anna Rubartelli Jürgen Ruland Armin Saalmüller Yvan Saeys Takashi Saito Shimon Sakaguchi Francisco Sala-de-Oyanguren Yvonne Samstag Sharon Sanderson Inga Sandrock Angela Santoni Ramon Bellmàs Sanz Marina Saresella Catherine Sautes-Fridman Birgit Sawitzki Linda Schadt Alexander Scheffold Hans U Scherer Matthias Schiemann Frank A Schildberg Esther Schimisky Andreas Schlitzer Josephine Schlosser Stephan Schmid Steffen Schmitt Kilian Schober Daniel Schraivogel Wolfgang Schuh Thomas Schüler Reiner Schulte Axel Ronald Schulz Sebastian R Schulz Cristiano Scottá Daniel Scott-Algara David P Sester T Vincent Shankey Bruno Silva-Santos Anna Katharina Simon Katarzyna M Sitnik Silvano Sozzani Daniel E Speiser Josef Spidlen Anders Stahlberg Alan M Stall Natalie Stanley Regina Stark Christina Stehle Tobit Steinmetz Hannes Stockinger Yousuke Takahama Kiyoshi Takeda Leonard Tan Attila 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Eur J Immunol 2019 Oct;49(10):1457-1973

Max Planck Institute for Infection Biology, Berlin, Germany.

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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http://dx.doi.org/10.1002/eji.201970107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350392PMC
October 2019

Monitoring of Measurable Residual Disease in Multiple Myeloma by Multiparametric Flow Cytometry.

Curr Protoc Cytom 2019 09 17;90(1). Epub 2019 Jul 17.

Roswell Park Comprehensive Cancer Center, Department of Flow and Image Cytometry, Elm & Carlton Streets, Buffalo, New York 14263.

Recent interest in high sensitivity multiple myeloma (MM) measurable residual disease (MRD) testing is a direct consequence of the high-quality responses achieved using novel therapeutic agents and better treatment strategies. Traditional diagnostic measures such as immunohistochemistry and morphology have detection sensitivities of only 10 - 10, which do not reliably predict progression free survival (PFS) or overall survival (OS) after these treatments. Contemporary monitoring of MM MRD has switched to more sensitive platforms such as quantitative allele-specific oligonucleotide polymerase chain reaction (ASO-qPCR), next-generation sequencing (NGS), and multiparametric flow cytometry (MFC). Though both ASO-qPCR and NGS have excellent detection sensitivities (10 - 10), both technologies have lower applicability when compared to MFC. Conventional MFC can easily reach a detection sensitivity of 10 and when optimized can achieve a sensitivity of 10 - 10. Current consensus guidelines require a minimum of 2 million and recommend 5 million events be acquired to reach a minimum sensitivity of 10. As conventional immunophenotyping protocols are unable to attain these numbers, alternative MFC staining procedures are required. This manuscript describes two high-sensitivity MFC approaches that can be used for MM MRD testing.
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http://dx.doi.org/10.1002/cpcy.63DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788635PMC
September 2019

Using Point-of-Care Ultrasound on Home Visits: The Home-Oriented Ultrasound Examination (HOUSE).

J Am Geriatr Soc 2019 12 6;67(12):2662-2663. Epub 2019 Oct 6.

Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1111/jgs.16188DOI Listing
December 2019

Correction: Immune profiling in diffuse large B-cell lymphoma and mantle cell lymphoma patients treated with autologous hematopoietic cell transplant.

Bone Marrow Transplant 2020 Jan;55(1):272

Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41409-019-0647-5DOI Listing
January 2020

Myeloablation followed by autologous stem cell transplantation normalises systemic sclerosis molecular signatures.

Ann Rheum Dis 2019 10 7;78(10):1371-1378. Epub 2019 Aug 7.

Hematologic Malignancy and Cellular Therapy, Duke University, Durham, North Carolina, USA.

Objective: In the randomised scleroderma: Cyclophosphamide Or Transplantation (SCOT trial) (NCT00114530), myeloablation, followed by haematopoietic stem cell transplantation (HSCT), led to improved clinical outcomes compared with monthly cyclophosphamide (CYC) treatment in systemic sclerosis (SSc). Herein, the study aimed to determine global molecular changes at the whole blood transcript and serum protein levels ensuing from HSCT in comparison to intravenous monthly CYC in 62 participants enrolled in the SCOT study.

Methods: Global transcript studies were performed at pretreatment baseline, 8 months and 26 months postrandomisation using Illumina HT-12 arrays. Levels of 102 proteins were measured in the concomitantly collected serum samples.

Results: At the baseline visit, interferon (IFN) and neutrophil transcript modules were upregulated and the cytotoxic/NK module was downregulated in SSc compared with unaffected controls. A paired comparison of the 26 months to the baseline samples revealed a significant decrease of the IFN and neutrophil modules and an increase in the cytotoxic/NK module in the HSCT arm while there was no significant change in the CYC control arm. Also, a composite score of correlating serum proteins with IFN and neutrophil transcript modules, as well as a multilevel analysis showed significant changes in SSc molecular signatures after HSCT while similar changes were not observed in the CYC arm. Lastly, a decline in the IFN and neutrophil modules was associated with an improvement in pulmonary forced vital capacity and an increase in the cytotoxic/NK module correlated with improvement in skin score.

Conclusion: HSCT contrary to conventional treatment leads to a significant 'correction' in disease-related molecular signatures.
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http://dx.doi.org/10.1136/annrheumdis-2019-215770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167108PMC
October 2019

IL12 and IFNγ secretion by donor mononuclear cells in response to host antigens may predict acute GVHD after HSCT.

Immunobiology 2019 09 20;224(5):659-665. Epub 2019 Jul 20.

Medical oncology Departments, NCI, Cairo University, Egypt.

One persistent problem of allogeneic hematopoietic stem cell transplantation (HSCT) is acute graft versus host disease (GVHD). The role of cytokines in the pathogenesis of GVHD has been acknowledged. We aimed, in the current study, to investigate the possibility of prediction of acute GVHD through investigating the pattern of interleukin 12 (IL12) and interferon gamma (IFNγ) production of both patients' origin and donors' origin. A total of 45 patients, receiving allogeneic peripheral blood (PB) stem cells from an identical sibling, were included in the study. Patients' plasma was collected after conditioning, during aplastic phase (representing patients' origin) and after engraftment (representing donors' origin). In addition an aliquot from the graft was used as responders in mixed lymphocyte culture (MLC) for 3 days with patients' mitomycin-treated mononuclear cells as stimulators. Culture supernatant was used for detection of IL12 and IFNγ of donors' origin. Fourteen patients developed acute GVHD. In culture supernatant, IL12 was detectable in 7/14 cases with and in none of 31 cases without acute GVHD (p= <0.001). The corresponding figures for IFNγ were 10/14 and 3/31 with significantly higher IFNγ level in cases with than in cases without acute GVHD (p = 0.001). At engraftment the corresponding figures were 7/14 and 5/31 for IL12 and 11/14 and 7/31 for IFNγ with significantly higher cytokine levels in cases with acute GVHD (p = 0.008 and p = 0.001 respectively). At a cutoff of 0.89 pg/ml, IL12 in culture supernatant may predict acute GVHD with absolute specificity of 100% and a sensitivity of 50%. In conclusion, IL12 and IFNγ of donors' origin not of patients' origin may predict the occurrence of acute GVHD. The MLC model may allow prediction of acute GVHD upfront before conditioning of the patient or mobilization of the donor.
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http://dx.doi.org/10.1016/j.imbio.2019.07.001DOI Listing
September 2019

Developing an opioid curriculum for medical students: A consensus report from a national symposium.

Subst Abus 2020 17;41(4):425-431. Epub 2019 Jul 17.

Meyers Primary Care Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

In June 2018, the Warren Alpert Medical School of Brown University hosted a national, multidisciplinary, interprofessional symposium on opioid curricula in undergraduate medical education. This article presents the consensus of an interprofessional group who attended a session focused on elements of an opioid curriculum, including key areas of content, teaching modalities, and learner assessment. This report also includes further directions and next steps for undergraduate medical education collaboration on opioid curricula.
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http://dx.doi.org/10.1080/08897077.2019.1635971DOI Listing
July 2019

Immune profiling in diffuse large B-cell lymphoma and mantle cell lymphoma patients treated with autologous hematopoietic cell transplant.

Bone Marrow Transplant 2020 01 21;55(1):77-85. Epub 2019 Jun 21.

Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

This is the first longitudinal study of immune profiles and autologous hematopoietic cell transplant (AHCT) survival in B-cell non-Hodgkin lymphoma (B-NHL) patients and the effect of plerixafor mobilization on immune reconstitution in this population. A comprehensive immunophenotyping panel was performed in 104 consecutive adult B-NHL patients (58% diffuse large B cell and 42% mantle cell) who received AHCT (1/2008-11/2014), at a median of 28 days pre-AHCT (N = 104) and Day +100 (N = 83) post-AHCT. Median follow-up post-AHCT was 61 months (range: 8-120 months). Compared to patients mobilized with filgrastim and plerixafor, patients mobilized with filgrastim alone had a higher proportion of CD4+ naïve (p = 0.006) and CD8+ central memory T-cells (p = 0.006) pre-AHCT. For patients transplanted in complete remission (CR), a higher proportion of CD8+ effector memory T-cells pre-AHCT was associated with worse progression-free survival (PFS; p < 0.01) and overall survival (OS; p < 0.01). A higher ratio of CD8:CD4+ central memory T-cells pre-AHCT was associated with worse PFS (p < 0.0001) and OS (p = 0.0034). This same ratio measured post-AHCT among patients in CR on Day +100 was associated with worse and OS (p = 0.008) but not PFS (p = not significant). These immune subsets are complementary biomarkers which identify patients transplanted in CR who have poor survival prognoses and may warrant further clinical interventions.
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http://dx.doi.org/10.1038/s41409-019-0591-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925359PMC
January 2020

Digital brief interventions for risky drinkers are not the panacea: A pilot study exploring barriers for its implementation according to professionals' perceptions.

Health Informatics J 2020 06 18;26(2):925-933. Epub 2019 Jun 18.

University of Barcelona, Spain.

Digital brief interventions have emerged as an instrument to improve the implementation of Screening, Brief Intervention and Referral to Treatment programs for risky drinkers. However, trials in Catalonia have been unsuccessful. This study was aimed at researching professionals' perceptions regarding the usefulness of digital brief interventions in overcoming traditional barriers of face-to-face Screening, Brief Intervention and Referral to Treatment and new barriers posed by the use of digital brief interventions. Professionals who participated in the Effectiveness of primary care based Facilitated Access to alcohol Reduction website (EFAR)digital brief intervention clinical trial were surveyed on April 2017 on the following areas: (1) satisfaction, (2) usefulness, (3) perceived ability of digital interventions on overcoming traditional barriers and (4) perceived new barriers of digital interventions. Sixty-eight professionals completed the survey. Univariate and multivariate analyses were performed using the level of professional engagement with the project as the dependent variable, barriers as independent variables and socio-demographic characteristics as covariables. Of all professionals, 79.4 percent were satisfied with their participation in the project, but only 26.5 percent perceived the website as useful. Low engagement was associated with the perceived lack of feedback (0.22; 95% confidence interval: 0.05 -0.88), perception that it was difficult to use among the elderly(0.22; 95 confidence interval: 0.05 -0.091) and among low socioeconomic population (0.14; 95% confidence interval: 0.03 -0.64). The majority of the participants indicated that digital brief intervention for risky drinkers succeeded in overcoming most of the traditional barriers. However, new barriers emerged as difficulties for implementing digital brief interventions in the Catalan Primary Health Care System. Usefulness perception is a key factor, which must be addressed in any proposed intervention in primary care.
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http://dx.doi.org/10.1177/1460458219855177DOI Listing
June 2020

Quality of molecular detection of vancomycin resistance in enterococci: results of 6 consecutive years of Quality Control for Molecular Diagnostics (QCMD) external quality assessment.

Eur J Clin Microbiol Infect Dis 2019 Sep 28;38(9):1633-1641. Epub 2019 May 28.

Department of Microbiology, National Reference Centre for Vancomycin-resistant Enterococci, University Hospital Antwerp, Edegem, Belgium.

The quality of PCR to detect vancomycin-resistant enterococci (VRE) was evaluated by analysing their performance in six consecutive external quality assessment (EQA) schemes, organized annually since 2013 by Quality Control for Molecular Diagnostics. VRE EQA panels consisted of 12-14 heat-inactivated samples. Sensitivity was tested with vanA-positive Enterococcus faecium (E. faecium), vanB-positive E. faecium, E. faecalis or E. gallinarum or vanC-positive E. gallinarum in different concentrations. Vancomycin-susceptible enterococci, Staphylococcus aureus or sample matrix was used to study the specificity. Participants were asked to report the VRE resistance status of each sample. The detection rate of vanA-positive samples was already 95% in the 2013 EQA panel (range 94-97%) and remained stable over the years. The 2013 detection rate of vanB-positive samples was 82% but increased significantly by more than 10% in subsequent years (96% in 2014, 95% in 2015, 92% in 2016 and 93% in 2017/2018, p < 0.05). The vanC detection rate by the limited number of assays specifically targeting this gene was lower compared to vanA/B (range 55-89%). The number of false positives in the true-negative sample (8% in 2013 to 1.4% in 2018) as well as the van-gene-negative bacterial samples (4% in 2013 to 0% in 2018) declined over the years. In the six years of VRE proficiency testing to date, the detection of vanA-positive strains was excellent and an increased sensitivity in vanB detection as well as an increase in specificity was observed. Commercial and in-house assays performed equally well.
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http://dx.doi.org/10.1007/s10096-019-03591-2DOI Listing
September 2019

Moving Ahead: What's Next for the eGEMs Community.

Authors:
Paul Wallace

EGEMS (Wash DC) 2019 May 16;7(1):22. Epub 2019 May 16.

AcademyHealth, US.

, in close partnership with our key sponsor and publisher, AcademyHealth, has provided a window to the transformational impact of electronic health data (EHD) on how we pursue health and deliver healthcare. This commentary traces key milestones in that journey and announces the next chapter for this community and the critical work it produces.
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http://dx.doi.org/10.5334/egems.313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524546PMC
May 2019

Factors affecting engagement of primary health care professionals and their patients in facilitated access to online alcohol screening and brief intervention.

Int J Med Inform 2019 07 24;127:95-101. Epub 2019 Apr 24.

GRAC. Addictions Unit, Department of Psychiatry, Clinical Institute of Neuroscience, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), RETICS (Red de Trastornos Adictivos), University of Barcelona, Villarroel 170, 08026, Barcelona, Spain. Electronic address:

Objective: Understanding the impact of Level of Information and Communication Technology Use, computer self-efficacy and perceived product usability of healthcare professionals regarding an alcohol consumption reduction website on facilitated access defined as referring patients to the webpage.

Methods: 52 nurses and 41 general practitioners were assessed before patient recruitment started, using a questionnaire designed to assess socio-demographic characteristics, professional engagement to the website, Level of Information and Communication Technology Use, Computer self-efficacy ("the judgment of one's capability to use a computer") and Perceived product usability ("the extent to which a product can be used by specified users to achieve specified goals with effectiveness, efficiency, and satisfaction in a specified context of use"). Dependent variable was the self-report of number of brochures distributed to patients.

Results: Professionals' engagement with facilitated access measured by brochures handed out was not predicted by Perceived product usability, Level of Information and Communication Technology Use or Computer self-efficacy. Professionals who had actively engaged with the website (customization) provided significantly more brochures compared with those who had not (Coefficient B 15.7 CI95% 3.5-27.8). Professional's socio-demographic characteristics did not predict engagement in facilitated access.

Conclusion: Professionals' Perceived product usability, Level of Information and Communication Technology Use and Computer self-efficacy were not associated to facilitated access. Active early engagement of health professionals with the website (customization) is a key predictor of subsequent engagement with facilitated access.

Practice Implications: Computer Self-Efficacy, Level of Information and Communication Technology Use and Perceived Product Usability are irrelevant for facilitated access and efforts should be focused on taking time to collaborate with providers and convincing them about the usefulness of the intervention (including customization). Website customization by health care professionals is a promising predictor of engagement.
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http://dx.doi.org/10.1016/j.ijmedinf.2019.04.018DOI Listing
July 2019

We've Only Just Begun - Insights from a 25-Year Journey to Accelerate Health Care Transformation Through Delivery System Research.

EGEMS (Wash DC) 2019 Apr 24;7(1):19. Epub 2019 Apr 24.

HealthPartners Institute, US.

Even though it is well known that quality, safety, and patient-centeredness of health care can be improved, leveraging the organizational apparatus of a care delivery environment to render improvement in a consistent and comprehensive manner has proven difficult. The Health Care Systems Research Network (HCSRN), which began as the HMO Research Network, emerged from a desire to improve health and study problems in health care in a systematic and collaborative way, spurring the delivery of true evidence-informed medicine. The HCSRN has honed network-wide data resources, a collaborative culture, and shared infrastructure, enabling multicenter health care research that is often more difficult for researchers working in less integrated settings and across organizational boundaries. The HCSRN's 25-year track record confers both an opportunity and obligation to share what we have learned through our research. Considering the quarter-century since the HCSRN was established, we describe three evolving areas-health data, new health care models, and diversified research teams that must be thoughtfully harnessed to realize a transformed health care ecosystem that generates and learns with research.
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http://dx.doi.org/10.5334/egems.310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484369PMC
April 2019

Palestinian health care is a global responsibility.

Lancet 2019 03;393(10177):1204

Department of Primary Care and Population Health, University College London, London, UK.

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http://dx.doi.org/10.1016/S0140-6736(19)30222-3DOI Listing
March 2019

Use of Phenobarbital in Alcohol Withdrawal Management - A Retrospective Comparison Study of Phenobarbital and Benzodiazepines for Acute Alcohol Withdrawal Management in General Medical Patients.

Psychosomatics 2019 Sep - Oct;60(5):458-467. Epub 2019 Feb 14.

Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD Massachusetts General Hospital, Boston, MA; Department of Psychiatry, Harvard Medical School, Boston, MA.

Background: Benzodiazepine-based protocols offer a standard of care for management of alcohol withdrawal, though they may not be safe or appropriate for all patients. Phenobarbital, a long-acting barbiturate, presents an alternative to conventional benzodiazepine treatment, though existing research offers only modest guidance to the safety and effectiveness of phenobarbital in managing alcohol withdrawal syndrome (AWS) in general hospital settings.

Methods: To compare clinical effectiveness of phenobarbital versus benzodiazepines in managing symptoms of alcohol withdrawal, we conducted a retrospective chart review of 562 patients admitted over a 2-year period to a general hospital and treated for AWS. The development of AWS-related complications (seizures, alcoholic hallucinosis, and alcohol withdrawal delirium) post-treatment initiation was the primary outcome examined in both treatment groups. Additional outcomes measured included hospital length of stay, intensive care unit (ICU) admission rates/length of stay, medication-related adverse events, and discharge against medical advice.

Results: Despite being significantly more likely to have a history of prior complications related to AWS (including seizures and delirium), patients initiated on phenobarbital (n = 143) had overall similar primary and secondary treatment outcomes to those in the benzodiazepine treatment protocol (n = 419). Additionally, a subset of patients (n = 16) initially treated with benzodiazepines displayed signs of treatment nonresponse, including significantly higher rates of AWS-related delirium and ICU admission rates, but were well-managed following transition to the phenobarbital protocol.

Conclusion: The data from this retrospective chart review lend further support to effectiveness and safety of phenobarbital for the treatment and management of AWS. Further randomized controlled trials are warranted.
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http://dx.doi.org/10.1016/j.psym.2019.02.002DOI Listing
July 2020

Impact of conditioning regimen on peripheral blood hematopoietic cell transplant.

World J Clin Oncol 2019 Feb;10(2):86-97

Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States.

Aim: To investigate infused hematopoietic cell doses and their interaction with conditioning regimen intensity +/- total body irradiation (TBI) on outcomes after peripheral blood hematopoietic cell transplant (PBHCT).

Methods: Our retrospective cohort included 247 patients receiving a first, T-replete, human leukocyte antigen-matched allogeneic PBHCT and treated between 2001 and 2012. Correlations were calculated using the Pearson product-moment correlation coefficient. Overall survival and progression free survival curves were generated using the Kaplan-Meier method and compared using the log-rank test.

Results: Neutrophil engraftment was significantly faster after reduced intensity TBI based conditioning [reduced intensity conditioning (RIC) + TBI] and > 4 × 10 CD34+ cells/kg infused. A higher total nucleated cell dose led to a higher incidence of grade II-IV acute graft-versus-host disease in the myeloablative + TBI regimen group ( = 0.03), but no significant difference in grade III-IV graft-versus-host disease. A higher total nucleated cell dose was also associated with increased incidence of moderate/severe chronic graft-versus-host disease, regardless of conditioning regimen. Overall and progression-free survival were significantly better in patients with a RIC + TBI regimen and total nucleated cell dose > 8 × 10/kg (3 years, overall survival: 70% 38%, = 0.02, 3 years, progression free survival: 64% 38%, = 0.02).

Conclusion: TBI and conditioning intensity may alter the relationship between infused cell doses and outcomes after PBHCT. Immune cell subsets may predict improved survival after unmanipulated PBHCT.
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http://dx.doi.org/10.5306/wjco.v10.i2.86DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390118PMC
February 2019

Innovation Through Collaboration: Creation of a Combined Emergency and Internal Medicine Point-of-Care Ultrasound Fellowship.

J Ultrasound Med 2019 08 28;38(8):2209-2215. Epub 2018 Dec 28.

Division of Emergency Ultrasound, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

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http://dx.doi.org/10.1002/jum.14908DOI Listing
August 2019