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EgeUn###, Importance: Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster. Objective: To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients. Design, Setting, and Participants: Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT. Interventions: Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n = 922) or placebo (n = 924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter. Main Outcomes and Measures: The primary end point was occurrence of confirmed herpes zoster cases. Results: Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P, Cornell University University of Manchester Universitat de València University of Kansas Medical Center, KUMC University of Manchester College of Medicine, Korea University Chonnam National University, CNU North Carolina GlaxoSmithKline Foundation Università degli Studi del Piemonte Orientale, UPO Gilead Sciences Pfizer National Institute of Allergy and Infectious Diseases, NIAID Amgen Merck GlaxoSmithKline foundation, GSK National and Kapodistrian University of Athens Chung Hua University, CHU University of Melbourne Thomas Jefferson University, TJU National Center for Medical Rehabilitation Research, NCMRR Cancer Center, University of Colorado National Cancer Center Helsingin Yliopisto Hacettepe Üniversitesi Tufts Medical Center City, University of London, City Gachon University Chung Hua University, CHU Uniwersytet Jagiellonski Collegium Medicum Manchester Biomedical Research Centre, BRC China Medical University Hospital, CMUH Chonbuk National University Hospital Seoul National University Hospital, SNUH Universitair Medisch Centrum Utrecht, UMC Universiti Kebangsaan Malaysia University of Seoul, UOS University of Minnesota, UM Ankara Universitesi Cleveland Clinic Foundation, CCF City, University of London, City University of North Carolina at Chapel Hill, UNC-CH Kyungpook National University, KNU, Author Affiliations: GlaxoSmithKline, Wavre, Belgium (Bastidas, Campora, Lopez-Fauqued); Hospital Universitario 12 de Octubre, Madrid, Spain (de la Serna); GlaxoSmithKline, Rixensart, Belgium (El Idrissi); CureVac AG, Tübingen, Germany (Oostvogels); University Hospital of Montpellier, Montpellier, France (Quittet); Hospital Ramón y Cajal, Madrid, Spain (López-Jiménez); Ege University Medical School, Izmir, Turkey (Vural); Charles University Hospital, Prague, Czech Republic (Pohlreich); Rambam Health Care Campus, Haifa, Israel (Zuckerman); Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts (Issa); Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy (Gaidano); Chonnam National University Hwasun Hospital, Jellanamdo, Republic of Korea (J.-J. Lee); University of Kansas Cancer Center, Westwood (Abhyankar); Hospital Clínico Universitario, School of Medicine, University of Valencia, Valencia, Spain (Solano); Centro Integral Oncológico Clara Campal (CIOCC), Universidad CEU San Pablo, Madrid, Spain (Perez de Oteyza); Weill Medical College of Cornell University, New York, New York (Satlin); Department of Hematology and Oncology, Charité University Medical Center, Berlin, Germany (Schwartz); Preventive Medicine and Epidemiology Department, University Hospital Vall d’Hebron, Barcelona, Spain (Campins); Haematology Department, Manchester University NHS Foundation Trust, Manchester Royal Infirmary, Manchester, England (Rocci); Faculty of Biology, Medicine and Health, School of Medical Science, Division of Cancer Sciences, University of Manchester, Manchester, England (Rocci); Hospital de Donostia, San Sebastián, Spain (Vallejo Llamas); Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, Catholic University of Korea, Seoul, South Korea (D.-G. Lee); Hospital Ampang, Selangor, Malaysia (Tan); Royal Hobart Hospital, Hobart, Australia (Johnston); Department of Clinical Haematology, Austin Health, Heidelberg, Australia (Grigg); Fred Hutchinson Cancer Research Center, Seattle, Washington (Boeckh); Halozyme Therapeutics, San Diego, California (Heineman); University of Pennsylvania, Philadelphia (Stadtmauer); Duke University Medical Center, Durham, North Carolina (Sullivan). -- reported being employed by and holding stock options in GlaxoSmithKline (GSK). Dr El Idrissi reported being employed by and holding stock options in GSK. Dr Oostvogels reported being employed by GSK during conception and/or conduct of the study and being currently employed by CureVac AG; being an inventor on a patent owned by GSK relevant to recombinant zoster vaccine; and holding stock in GSK. Dr López-Jiménez reported receipt of grants from Hospital Ramon y Cajal. Dr Vural reported receipt of grants and personal fees from GSK. Dr Issa reported receipt of grants from GSK, Merck, and Astellas and personal fees from Akros Pharma. Dr Gaidano reported receipt of trial patient fees from GSK and personal fees from Abbvie, Roche, Gilead, Janssen, and Morphosys. Dr Perez de Oteyza reported receipt of grants from GSK, Pharmacyclics, Vivia-Biotech, Morphosys, and Helsinn; grants and personal fees from Roche, Janssen, Takeda, and Celgene; and personal fees from Servier and Gilead. Dr Satlin reported receipt of grants from GSK, Allergan, Merck, Biofire Diagnostics, and Biomerieux and consulting fees from Achaogen and Shionogi. Dr Schwartz reported receipt of grants from GSK and personal fees and nonfinancial support from Amgen, Basilea Pharmaceutica, Gilead, Jazz Pharmaceuticals, Merck Sharp & Dohme, and Pfizer. Dr Campins reported receipt of grants and personal fees from GSK; participation as an investigator in clinical trials from GSK and Novartis; and participation in expert meetings and symposiums organized by Pfizer, GSK, Sanofi-Pasteur, Merck Sharp & Dohme, and Novartis. Dr Rocci reported receipt of consultancy fees from Takeda and Sanofi and honoraria from Takeda, Celgene, Novartis, Amgen, and Janssen and advisory board membership for Novartis, Amgen, and Janssen. Dr Johnston reported receipt of personal fees from Roche, Janssen Cilag, Celgene, and Merck Sharp & Dohme. Dr Grigg reports advisory board membership for Novartis, Gilead, Roche, Merck Sharp & Dohme, Takeda, and Bristol-Myers Squibb. Dr Boeckh reported receipt of grants and personal fees from GSK, Merck, and Chimerix and personal fees from Clinigen. Dr Campora reported being an employee of GSK; owning shares in GSK; and receipt of personal fees from GSK. Dr Lopez-Fauqued reported being an employee of GSK. Dr Heineman reported being an employee of GSK during conception and/or conduct of the study; holding stock and stock options in GSK; being an inventor on a patent owned by GSK relevant to recombinant zoster vaccine; being a paid consultant for GSK. Dr Stadtmauer reported receipt of grants from GSK. Dr Sullivan reported receipt of grants and personal fees from GSK; personal fees from Kiadis Pharmaceutical and Roche Genentech; and a grant from the National Institute of Allergy and Infectious Diseases awarded to his university. No other disclosures were reported. -- (Hematology Department, National and Kapodistrian University of Athens, “Laikon” General Hospital, Athens, Greece), Veli-Jukka Anttila, MD, PhD (Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland), Mickael Aoun, MD (Microbiologie Infectious Diseases, Institut Jules Bordet, Bruxelles, Belgium), Ibrahim Barista, MD (Hacettepe University Medical Faculty, Ankara, Turkey), Leanne Berkahn, MB, ChB (Department of Heamatology, Auckland City Hospital, Grafton, New Zealand), Adrian J. C. Bloor, PhD, FRCP (Haematology and Transplant Unit, Christie NHS Foundation Trust, Manchester, England), Raewyn Broady, MB, ChB (Vancouver General Hospital, Vancouver, British Columbia, Canada), Peter Brossart, MD (Universitaetsklinikum Bonn, Bonn, Germany), Francis K. Buadi, MB, ChB (Mayo Clinic, Rochester, Minnesota), Claude-Eric Bulabois, MD (Service d’Hématologie, CHU de Grenoble–Hôpital Michallon, Grenoble, France), Guy Cantin, MD (CHU de Quebec–Hopital de l’Enfant-Jesus, Quebec City, Quebec, Canada), Claudia Cellini, MD (UO di Ematologia, Ospedale Santa Maria delle Croci, Ravenna, Italy), Pranatharthi Haran Chandrasekar, MD (Karmanos Cancer Institute, Detroit, Michigan), Thomas Chauncey, MD (Veterans Administration Puget Sound Health Care System, Seattle, Washington), Antonio Cuneo, MD (Unità Operativa di Ematologia, Azienda Ospedale Universitaria Arcispedale S. Anna, Venice, Italy), Sanjeet Singh Dadwal, MD (City of Hope National Medical Center, Duarte, California) , Michael Dickinson, MBBS(hons), DMedSci, FRACP, FRCPA (Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia), HyeonSeok Eom, MD, PhD (National Cancer Center, Kyunggi-do, Korea), Albert Esquirol Sanfeliu, MD (Hospital Santa Creu i Sant Pau, Barcelona, Spain), Christelle Ferra Coll, MD, PhD (Hospital Germans Trias i Pujol, Barcelona, Spain), Phyllis R. Flomenberg, MD (Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania), Ana Pilar González-Rodríguez, MD, PhD (Hospital Central de Asturias, Oviedo, Spain), David J. Gottlieb, MD (Department of Haematology, Westmead Hospital, Westmead, Australia), Sigal Grisariu, MD (Hadassah Medical Center, Jerusalem, Israel), Andreas Guenther, MD (Universitaetsklinikum Schleswig-Holstein, Kiel, Germany), Jonathan Gutman, MD (University of Colorado Cancer Center, Aurora), Uwe Hahn, MD (Department of Haematology and Oncology, Queen Elizabeth Hospital, Woodville, Australia), Werner J. Heinz, MD (Universitaetsklinikum Wuerzburg, Wuerzburg, Germany), Inmaculada Heras, MD, PhD (Hospital General Universitario J. M. Morales Meseguer, Murcia, Spain), Takashi Ikeda, MD, PhD (Shizuoka Cancer Center, Shizuoka, Japan), Isidro Jarque, MD, PhD (Hospital Universitario y Politécnico La Fe, Valencia, Spain), Meinolf Karthaus, MD (Staedtisches Krankenhaus Muenchen, Muenchen, Germany), Tessa Kerre, MD, PhD (Hematologie, UZ Gent, Gent, Belgium), Alexander Kiani, MD (Klinikum Bayreuth, Bayreuth, Germany), Andreas K. Klein, MD (Tufts Medical Center, Boston, Massachusetts), Grzegorz Kofla, MD (Charite, Berlin, Germany), Irina V. Kryuchkova, MD, PhD (Research Institute of Clinical Immunology, Novosibirsk, Russia), Ching-Yuan Kuo, MD (Chang Gung Memorial Hospital–Kaoshiung, Kaohsiung, Taiwan), John Kuruvilla, MD (Princess -- Margaret Hospital, Toronto, Ontario, Canada), Aleksey Kuvshinov (Russian Hematology and Transfusiology Research Center, St Petersburg, Russia), Jae-Yong Kwak, MD, PhD (Chonbuk National University Hospital, Jeonju, South Korea), Jae Hoon Lee, MD, PhD (Hematology, Gachon University Gil Hospital, Incheon, South Korea), Stéphane Lepretre, MD (Département d’Hématologie, Centre Henri Becquerel, Rouen, France), Albert Kwok-Wai Lie, MBBS (Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Medicine, Queen Mary Hospital, Hong Kong, China), Alessandro Lucchesi, MD (Oncologia Medica, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy), Johan Maertens, MD, PhD (Hematologie, UZ Leuven–Campus Gasthuisberg, Leuven, Belgium), Erik W. A. Marijt, MD, PhD (Leids UMC, Leiden, Netherlands), Carmen Martínez Muñoz, MD (Hospital Clinic i Provincial, Barcelona, Spain), Mariagrazia Michieli, MD (UOS Dipartimento Terapia Cellulare-Chemioter Alte Dosi, Centro di Riferimento Oncologico IRCCS, Aviano, Italy), Samuel T. Milliken, MBBS (Department of Haematology, St Vincent’s Hospital, Darlinghurst, Australia), Noël Milpied, MD (Hématologie Clinique et Thérapie Cellulaire, CHU de Bordeaux–Hôpital du Haut Lévêque, Pessac, France), Jorge Monserrat Coll, MD (Hospital Virgen de la Arrixaca, Murcia, Spain), Sherif Beniameen Mossad, MD (Department of Infectious Diseases, Cleveland Clinic Foundation, Cleveland, Ohio), John Murphy, MB, ChB (Monklands Hospital, Airdrie, Scotland), María Belén Navarro Matilla, MD (Hospital Puerta de Hierro, Madrid, Spain), Jan Novak, MD, PhD (Oddeleni Klinicke Hematologie, Fakultni Nemocnice Kralovske Vinohrady, Prague, Czech Republic), Harold J. Olney, MD, CM (Centre Hospitalier de l’Universite de Montreal, Montreal, Quebec, Canada), Raquel Oña Navarrete, MD, PhD (M. D. Anderson, Madrid, Spain), María Jesús Pascual Cascón, MD (Hospital Carlos Haya, Málaga, Spain), Andy Peniket (Oxford University Biomedical Research Centre, Oxford, England), Ganeva Penka (CTH Sofia, Sofia, Bulgaria), Beata Piatkowska-Jakubas, DSc, MD (Department of Haematology, Jagiellonian University Medical College, Krakow, Poland), Marta Polo Zarzuela, MD (Hospital Clínico San Carlos, Madrid, Spain), Dimas Quiel, MD (Complejo Hospitalario Dr Arnulfo Arias Madrid, Panama City, Panama), Scott D. Rowley, MD, FACP (John Theuer Cancer Center, Hackensack University Medical Center, Hackensack, New Jersey), Waleed Sabry, MD, MSc, PhD (Saskatoon Cancer Centre, Saskatoon, Saskatchewan, Canada), Tommi Mikael Salmi, MD (Sisatautien Klinikka, Hematologian Yksikko os 015, Turun Yliopistollinen Keskussairaala, Turku, Finland), Dominik L. D. Selleslag, MD (Hematologie, AZ Sint-Jan Brugge– Oostende AV–Campus Sint-Jan, Brugge, Belgium), Thomas C. Shea, MD (Division of Hematology and Medical Oncology, University of North Carolina at Chapel Hill), Gerda Silling, MD (Universitaetsklinikum Muenster, Muenster, Germany), Ulla Marjatta Sinisalo, MD, PhD (Hematology Unit, Department of Internal Medicine, Tampere University Hospital, Tampere, Finland), Sang Kyun Sohn, MD, PhD (School of Medicine, Kyungpook National University, Daegu, South Korea), Peter Staib, MD, PhD (St Antonius Hospital, Eschweiler, Germany), Jeff Szer, MBBS (Haematology Department, Royal Melbourne Hospital, Parkville, Australia), Koen Theunissen, MD (Hematologie, Jessa Ziekenhuis–Campus Virga Jesse, Hasselt, Belgium), Pervin Topcuoglu, MD (Ankara University, Ankara, Turkey), Natalya G. Tyurina, PhD (Moscow Oncology Reserach Institute NA Herzen, Moscow, Russia), Mikhail Uvarov, MD, PhD (City Clinical Hospital No. 31, St Petersburg, Russia), Fadilah S. Abdul Wahid, PhD (Department of Medicine, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia), Lucrecia Yáñez San Segundo, MD, PhD (Hospital Marqués de Valdecilla, Santander, Spain), Zeynep Arzu Yegin (Gazi University Medical Faculty, Ankara, Turkey), Su-Peng Yeh, MD (Department of Hematology, China Medical University Hospital, Taichung, Taiwan), Sze-Fai Yip, MD (Department of Medicine and Geriatrics, Tuen Mun Hospital, Tuen Mun, Hong Kong), Sung Soo Yoon, MD, PhD (Seoul National University Hospital, Seoul, South Korea), Jo-Anne H. Young, MD (University of Minnesota, Minneapolis), Pierre Zachée, MD, PhD (Hematologie-Oncologie, Ziekenhuisnetwerk Antwerpen, ZNA Stuivenberg and ZNA Middelheim, Antwerpen, Belgium), Francesco Zaja, MD (Clinica Ematologica, Azienda Ospedaliero Universitaria S. Maria Misericordia, Udine, Italy). Principal investigators and study sites are listed in eTable 9 and committees and GSK team members are listed in the eBox in Supplement 3. -- --

The primary aim of this study was to describe the use of primary anti-infective prophylaxis (AP) in common clinical practice in patients affected by immune thrombocytopenia (ITP) and treated with RTX. Population studied consisted of patients affected by ITP (age ≥ 18 years) who had received at least one dose of RTX from January 2008 to June 2018. Five Italian haematology centres participated in the current study. Data were retrospectively collected: demographic data (age, gender), concomitant comorbidities and previous therapies for ITP, characteristics of AP, the occurrence of infections and their management. The ITP cohort consisted of 67 patients sub-grouped into two categories according to the administration of AP: (1) treated with AP (N= 34; 51%) and (2) not treated with AP (N=33, 49%). AP consisted of combined trimethoprim/sulfamethoxazole (TMP/SMX) and acyclovir (AC) in half of patients. TPM/SMX as a single agent was adopted in 32% patients and one patient received only AC. Overall, infections were experienced in 15% of patients during follow-up with a similar proportion in the 2 groups (treated and not treated) of patients (14.7% vs 15%). Clinical course of infections was however, less severe in patients treated with AP, where all infections were grade 2 and did not require hospitalization. In neither group of patients was reported Pneumocystis pneumonia. In conclusion, despite the absence of clear evidence, our analysis shows that AP in patients with ITP receiving RTX is frequently adopted, even if in the absence of well-defined criteria. Prophylaxis administration is quite consistent within the same haematological Center; thus, it seems related to clinicians' experience.

Background: Blood culturing remains the mainstream tool to inform an appropriate treatment in hospital-acquired bloodstream infections and to diagnose any bacteremia. Methods: A retrospective investigation on the prevalence of Gram-negative bacteria (GNB) and their resistance in hospitalized patients by age, sex, and units from blood cultures (BCs) was conducted from January 2018 to April 2020 at Sant’Elia hospital, Caltanissetta, southern Italy. We divided the patient age range into four equal intervals. Results: Multivariate demographic and microbiological variables did not show an association between bacteria distributions and gender and age. The distribution by units showed a higher prevalence of Klebsiella pneumoniae and Acinetobacter baumannii in the intensive care unit (ICU) and Escherichia coli in the non-intensive care units (non-ICUs). The analysis of antibiotic resistance showed that E. coli was susceptible to a large class of antibiotics such as carbapenem and trimethoprim-sulfamethoxazole. K. pneumoniae showed a significant susceptibility to colistin, tigecycline, and trimethoprim-sulfamethoxazole. From the survival analysis, patients with E. coli had a higher survival rate. Conclusions: The authors stress the importance of the implementation of large community-level programs to prevent E. coli bacteremia. K. pneumoniae and E. coli susceptibility patterns to antibiotics, including in the prescription patterns of general practitioners, suggest that the local surveillance and implementation of educational programs remain essential measures to slow down the spread of resistance and, consequently, increase the antibiotic lifespan.

Current cytoreductive and antithrombotic strategies in MPNs are mostly based on cell counts and on patient’s demographic and clinical history. Despite the numerous studies conducted on platelet function and on the role of plasma factors, an accurate and reliable method to dynamically quantify the hypercoagulability states of these conditions is not yet part of clinical practice. Starting from our experience, and after having sifted through the literature, we propose an in-depth narrative report on the contribution of the clonal platelets of MPNs—rich in tissue factor (TF)—in promoting a perpetual procoagulant mechanism. The whole process results in an unbalanced generation of thrombin and is self-maintained by Protease Activated Receptors (PARs). We chose to define this model as a “circulating wound”, as it indisputably links the coagulation, inflammation, and fibrotic progression of the disease, in analogy with what happens in some solid tumours. The platelet contribution to thrombin generation results in triggering a vicious circle supported by the PARs/TGF-beta axis. PAR antagonists could therefore be a good option for target therapy, both to contain the risk of vascular events and to slow the progression of the disease towards end-stage forms. Both the new and old strategies, however, will require tools capable of measuring procoagulant or prohaemorrhagic states in a more extensive and dynamic way to favour a less empirical management of MPNs and their potential clinical complications.

The last decade has been very important for the quantity of preclinical information obtained regarding chronic myeloproliferative neoplasms (MPNs) and the following will be dedicated to the translational implications of the new biological acquisitions. The overcoming of the mechanistic model of clonal evolution and the entry of chronic inflammation and dysimmunity into the new model are the elements on which to base a part of future therapeutic strategies. The innate immune system plays a major role in this context. Protagonists of the initiation and regulation of many pathological aspects, from cytokine storms to fibrosis, the NLRP3 and AIM2 inflammasomes guide and condition the natural history of the disease. For this reason, MPNs share many biological and clinical aspects with non-neoplastic diseases, such as autoimmune disorders. Finally, cardiovascular risk and disturbances in iron metabolism and myelopoiesis are also closely linked to the role of inflammasomes. Although targeted therapies are already being tested, an increase in knowledge on the subject is desirable and potentially translates into better care for patients with MPNs.

The use of hydroxychloroquine (HCL) has been very common in countries with a rapid spread of coronavirus disease 2019 (COVID-19), although controversial and the subject of heated scientific discussions with implications for the whole society. This article is protected by copyright. All rights reserved.

INTRODUCTION: Primary Immune thrombocytopenia (ITP) in the elderly is a major clinical challenge which is increasingly frequent due to global ageing population. MATERIALS AND METHODS: To describe baseline ITP features, management, and outcome, a centralized electronic database was established, including data of 451 patients aged ≥60years that were treated from 2000 onwards and were observed for ≥1year (total observation of 2704 patient-years). RESULTS: At ITP diagnosis, median age was 71.1years (age≥75: 42.8%); 237 (53.9%) patients presented with haemorrhages (grade≥3: 7.5%). First-line therapy included prednisone (82.9%), dexamethasone (14.6%), thrombopoietin-receptor agonists (TRAs, 1.3%), and oral immunosuppressive agents (1.1%). Prednisone starting dose ≥1mg/kg/d (p=.01) and dexamethasone 40mg/d (p&nbsp

// Andrea Casadei Gardini 1, * , Silvia Carloni 2, * , Emanuela Scarpi 3 , Paolo Maltoni 4 , Romolo M. Dorizzi 4 , Alessandro Passardi 1 , Giovanni Luca Frassineti 1 , Pietro Cortesi 1 , Maria Benedetta Giannini 1 , Giorgia Marisi 2 , Dino Amadori 1 , Alessandro Lucchesi 1 1 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 2 Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 3 Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 4 Corelab Unit, AVR Laboratory, Cesena, Italy * These authors contributed equally to this work Correspondence to: Andrea Casadei Gardini, e-mail: andrea.casadei@irst.emr.it Keywords: metastatic colorectal cancer, high-sensitivity C-reactive protein, thrombosis, progression-free survival, overall survival Received: October 15, 2015 Accepted: January 24, 2016 Published: February 03, 2016 ABSTRACT Serum levels of C-reactive protein are (CRP) higher in patients with neoplastic conditions and numerous studies have been performed to clarify the etiologic and prognostic role of the high-sensitivity CRP (hs-CRP) in cancer. Our study was conducted on patients enrolled in the prospective randomized “Italian Trial in Advanced Colorectal Cancer (ITACa)” to assess hs-CRP levels and their impact on overall survival (OS) and progression-free survival (PFS). Serum samples from 132 ITACa patients were collected at baseline and 2 months after starting first-line chemotherapy. The supernatant was immediately transferred to cryovials and stored at –80°C. After thawing, hs-CRP was measured with the Cobas c501 analyzer. High levels of hs-CRP (≥ 13.1 mg/L) were associated with poorer median PFS ( p < 0.0001) and OS ( p < 0.0001) than low hs-CRP levels (< 13.1 mg/L). hs-CRP values in 107 patients were evaluated again after 2 months of therapy, revealing that patients with low hs-CRP levels in both baseline and second serum samples had the best median PFS and OS. Our study confirms the prognostic value of hs-CRP in patients with metastatic colorectal carcinoma.

Background: Sorafenib is a multi-targeted kinase inhibitor with a demonstrated activity in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC), and it is currently used for the treatment of these pathologies. Ongoing clinical trials are studying its activity in other malignancies, such as non-small-cell lung cancer (NSCLC). However, no biological marker is known to define either the sensitivity or resistance to the drug. Case presentation: Here we report a case of a patient with two synchronous tumors, HCC and NSCLC, with metastases in the contralateral lung and bone. The patient was treated with gemcitabine as first line, with a resulting progressive disease after two months, and then with sorafenib at standard dosage in the second line setting. After 6 months of treatment CT scan showed a partial response in the primary lesion of the lung, complete response of the metastasis in the contralateral lung, and stability of HCC. The patient had progression in the lung, liver and bone after 13 months of therapy. A molecular characterization of NSCLC and HCC lesions was performed, revealing a BRAF exon 11 mutation (G469V) only in NSCLC. We hypothesize that the response observed in NSCLC lesions could be due to the presence of BRAF mutation, and that this alteration could be responsible in determining sorafenib sensitivity. Conclusions: Results observed in this case encourage further research on the activity of sorafenib in both HCC and NSCLC, based on the presence of BRAF mutation. This could lead to a selection of HCC patients to be treated with this drug, and could help identify a novel treatment strategy for BRAF-mutated NSCLC patients.

Dear Editor, In the current clinical practice, minimal criteria to define thrombotic thrombocytopenic purpura (TTP) are the presence of signs of microangiopathic haemolytic anaemia and low platelet (PLT) count [1]. TTP relapses (20–50 % of cases) are defined as the recurrence of acute TTP symptoms 30 days after the first episode, while exacerbations occur within 30 days [2]. We here report on an atypical case of acquired TTP where minimal criteria were met only after many recurrent macrovascular ischemic events. A 42-year old Caucasian woman with a history of coronary and cerebral ischemic events was admitted on June 2013, following a recurrent transient ischemic attack (TIA). She had severe anaemia and thrombocytopenia with laboratory signs of intravascular haemolysis and mild renal impairment. In her past medical history, recurrent ischemic events occurred from 2008 to 2012, without known risk factors and regardless of treatment. The patient was treated with acetyl salicylic acid (100 mg daily) after the first ischemic event (stroke, in 2008) plus anticoagulation with warfarin after the third stroke (in 2010), with a good compliance . Screening for autoimmune disease, Factor V Leiden and Factor II (G20210A) gene mutations and circulating anticoagulants were normal. Blood cell count and peripheral blood smear did not show any significant abnormalities in the past, without evidence of schistocytes; a slight decrease in PLT count (92×109/L) was observed only once (in 2012), at that time, ADAMTS13 activity (ADAMTS-13: AC) was 65 %. At the current admission, ADAMTS-13: AC was 6 %, inhibitors were at high titer (2 Bethesda Units, BU). A genetic test for Upshaw-Schulman syndrome was normal. Therapeutic plasma exchange (TPE) and prednisone (1 mg/kg body weight) treatment was started and maintained until clinical and haematological remission [3]. TPE (Gambro®, Italy) was performed daily for 3 weeks with an increase of ADAMTS13: AC to 50 %. TTP exacerbated after 10 days, it was well controlled with weekly rituximab (375 mg/m body surface), for 4 weeks. A relapse occurred after 37 days with the patient presenting seizures: ADAMTS-13: AC, which was 54 % after the last treatment, had decreased to 6 %. A second course of weekly rituximab, followed by maintenance with azathioprine (50 mg twice daily for 10 days, then 50 mg, daily) was followed by clinical and haematological remission. Rituximab was re-administered for its previous rapid efficacy and to prevent further complications [4]. The patient is alive and free from recurrences for 18 months; azathioprine maintenance is still on course. ADAMTS13: AC is monitored every 4 months, and it ranges from 45 to 51 %; inhibitors are no longer detectable. * Alessandro Lucchesi alessandro.lucchesi@irst.emr.it

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Background: Systemic capillary leak syndrome is a rare disease with a high mortality rate. This syndrome is characterised by generalised edema, hypotension, hemoconcentration, and hypoproteinemia. The cause is the sudden onset of capillary hyperpermeability with extravasations of plasma from the intravascular to the extravascular compartment. We present the case of a patient who experienced two episodes of systemic capillary leak syndrome and pulmonary hypertension; the first after gemcitabine in an adjuvant setting and the second three years later after treatment with nab-paclitaxel for metastatic disease.Case presentation: A 65-year-old patient underwent a pancreatectomy in January 2010 for ductal carcinoma (pT3 N0 M0, stage IIa), followed by adjuvant chemotherapy. Seven days after the last cycle, she developed dyspnea associated with orthopnea and cough. A transthoracic cardiac ecocolordoppler was performed, with evidence of pulmonary hypertension (58 mmHg). Blood tests showed an increase in creatinine, pro-BNP and D-Dimer. She began high-dose diuretic therapy combined with cortisone. After a month, the patient was eupneic and the anasarca had resolved. We decided gradually to reduce the steroid and diuretic therapy. After ten days of the reduction, the patient began to re-present the same symptoms after treatment with gemcitabine. Corticosteroid therapy was restored with rapid clinical benefit and decreased pro-BNP after a week of treatment. After two years, the disease returned. As a first line treatment, it was decided to use nab-paclitaxel 100 mg/m2 weekly. After two doses, followed by approximately 14 days of treatment, the patient developed acute respiratory distress syndrome. The clinical suspicion was a relapse of capillary leak syndrome and treatment with a high-dose diuretic (furosemide 250 mg daily) was started combined with cortisone (40 mg methylprednisolone). The patient showed a progressive clinical benefit.Conclusions: In patients treated with gemcitabine and nab-paclitaxel who experience a sudden onset of diffuse edema with respiratory distress, capillary leak syndrome should be suspected. Immediate treatment with corticosteroids may be life-saving. © 2013 Casadei Gardini et al.; licensee BioMed Central Ltd.