COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Influence of training level on cervical cone size and resection margin status at conization : a retrospective study

Objective To explore whether a surgeons training level influences the rate of incomplete resections or the amount of resected cervical tissue in women treated with large loop excision of the transformation zone (LLETZ). Methods The present study is a retrospective analysis of the data of women who had undergone LLETZ for cervical intraepithelial neoplasia (CIN) within the years 20042008 at the Medical University of Vienna. Women were grouped according to the level of training of the operating surgeon (i.e, resident or staff gynecologist) and univariate and multivariable analyses were performed to identify independent risk factors for excessive cone volume, depth and incomplete resection (i.e., positive resection margin). Results Data of 912 women were analysed. Residents had a significantly larger cone volume [median 2681 (interquartile range 14724109) mm3] than staff gynecologists [2094 (13093402) mm3] (p=0.001) in univariate analysis. The depth of resection and the rate of incomplete resection were comparable between both groups. In a binary logistic multivariable analysis, the level of training as well as patients age was significantly associated with a cone volume larger than 2500 mm3. Conclusion Conization performed by residents as opposed to staff gynecologists does not compromise the procedures effectiveness but may expose women to a potential additional risk for adverse obstetrical outcomes due to excessive resection of cervical tissue.(VLID)358039

A double-blind, randomized clinical study to determine the efficacy of benzocaine 10% on histamine-induced pruritus and UVB-light induced slight sunburn pain

<div><p></p><p><i>Introduction</i>: This study aims to explore the efficacy of the topical application of 10% benzocaine for treating pruritus and pain as compared to vehicle ointment. <i>Methods</i>: Twenty male subjects were treated in a randomized double-blind fashion with the investigational medicinal product (IMPD) and vehicle. Immediately after the injection of 100 µg histamine on both arms, subjects received topical treatment and pruritus was subsequently assessed with visual analogue scale (VAS_pruritus) and Eppendorfer questionnaire. Ultraviolet B radiation (UVB) was administered on the back to induce slight sunburn. Twelve hours after UVB application again the IMPD was applied on the right or left upper back and vehicle on the other side and pain related to sunburn was measured with VAS_pain and pressure algometry. <i>Results</i>: A trend towards better reduction of pruritus was shown for benzocaine in VAS_pruritus. For the VAS_pain significant differences in group comparison (<i>p</i> = 0.02) were observed. Algometer measurements showed onset of pain reduction in the verum group after 20 min whereas in the vehicle-treated area pain relief occurred only after 60 min after application. <i>Conclusions</i>: The topically administered ointment containing 10% benzocaine was found superior over vehicle for treating pain, but not pruritus.</p></div

Strahlentherapie und Onkologie / Increased genitourinary fistula rate after bevacizumab in recurrent cervical cancer patients initially treated with definitive radiochemotherapy and image-guided adaptive brachytherapy

Hintergrund und Ziel Patientinnen mit Rezidiv eines Zervixkarzinoms (RecCC), die primär eine bildgesteuerte adaptive Brachytherapie (IGABT) und kombinierte Radiochemotherapie (RCHT) erhalten hatten, werden derzeit in unserem Institut mit einer Kombination aus Chemotherapie (CHT) und Bevacizumab (BEV) behandelt. Ziel dieser Studie war es, das Risiko für das Auftreten gastrointestinaler (GI) sowie urogenitaler (GU) Fisteln unter CHT sowie CHT + BEV zu analysieren. Patienten und Methode In diese retrospektive Datenanalyse wurden insgesamt 35 konsekutive Patientinnen mit RecCC, die primär mit RCHT und IGABT behandelt worden waren, inkludiert. Klinisch-pathologische Risikofaktoren für das Auftreten einer GI- sowie GU-Fistel wurden erhoben. Die Raten an Fistelbildungen in der CHT-Gruppe und in der Gruppe mit CHT + BEV wurden verglichen. Ergebnisse Von 35 Patientinnen erhielten 25 eine CHT und 10 CHT + BEV. Insgesamt wurde bei 6 Patientinnen eine Fistel diagnostiziert, davon 2 in der Gruppe mit CHT (8 %) und 4 in der mit CHT + BEV (40 %). GU-Fisteln entwickelten sich ausschließlich in der Gruppe mit CHT + BEV (3/4; 75 %). Von den 6 Patientinnen (83 %) mit Fistelbildung hatten 5 eine vorangehende invasive diagnostische Abklärung und 1 Patientin wurde einer neuerlichen Radiotherapie unterzogen. Ein Lokalrezidiv hatten 3/6 Patientinnen entwickelt. Weitere Risikofaktoren für die Entwicklung einer Fistel konnten nicht identifiziert werden. Schlussfolgerung Die zusätzliche Gabe von BEV zur CHT bei RecCC-Patienten, die primär mit IGABT und RCHT behandelt wurden, könnte möglicherweise zu einer erhöhten Rate an GU-Fisteln führen. Zukünftige Studien sollten Risikofaktoren für Fistelbildung untersuchen, um eine gründliche Patientenselektion für die Gabe von BEV bei RecCC zu ermöglichen.Background and purpose Patients with recurrent cervical cancer (RecCC) who received definitive radiochemotherapy including image-guided adaptive brachytherapy (IGABT) as primary treatment are currently treated in our institution with palliative intent by chemotherapy (CHT) combined with bevacizumab (BEV). We aim to evaluate the risk of gastrointestinal (GI)/genitourinary (GU) fistula formation in these patients. Materials and methods Data of 35 consecutive patients with RecCC treated initially with radiochemotherapy and IGABT were collected. Known and presumed risk factors associated with fistula formation were evaluated. Fistula rate was compared between patients receiving CHT or CHT+BEV. Results Of the 35 patients, 25 received CHT and 10 patients received CHT+BEV. Clinical characteristics were comparable. Fistulae were reported in 6 patients: two fistulae (8%) in the CHT group, four (40%) in the CHT+BEV group. GU fistula occurred in the CHT+BEV group only (3/4). Of these 6 patients with fistulae, 5 (83%) had undergone previous invasive procedures after the diagnosis of RecCC and 1 patient had undergone pelvic re-irradiation; 3/6 patients had developed a local recurrence. No other risk factors for fistula formation were identified. Conclusion In patients with RecCC after definitive radiochemotherapy including IGABT, the addition of BEV to CHT may increase the risk for GU fistula formation, particularly after invasive pelvic procedures. Future clinical studies are required to identify predictors for fistula formation to subsequently improve patient selection for the addition of BEV in the RecCC setting.(VLID)363265

Strahlentherapie und Onkologie / The value of pretreatment serum butyrylcholinesterase level as a novel prognostic biomarker in patients with cervical cancer treated with primary (chemo-)radiation therapy

Hintergrund Für erniedrigte Butyrylcholinesterase(BChE)-Spiegel, die üblicherweise im Rahmen von Leberschäden, Entzündungsreaktionen oder Mangelernährung auftreten, wurden kürzlich auch Assoziationen mit schlechterem Überleben in verschiedenen onkologischen Erkrankungen beschrieben. Das Ziel dieser Studie war, die prognostische Bedeutung von prätherapeutischen BChE-Serumspiegeln für das Überleben von Zervixkarzinompatientinnen unter primärer (Chemotherapie- [Chemo-])Radiotherapie zu untersuchen. Methoden Prätherapeutische BChE-Werte im Serum aller Zervixkarzinompatientinnen, die im Zeitraum von 1998 bis 2015 mit einer primären (Chemo)Radiotherapie behandelt wurden, wurden retrospektiv erhoben und mit klinisch-pathologischen Parametern sowie dem Therapieansprechen korreliert. In uni- und multivariaten Überlebensanalysen wurde der Zusammenhang zwischen erniedrigten BChE-Spiegeln und progressionsfreiem (PFS), tumorspezifischem (CSS) und Gesamtüberleben (OS) untersucht. Ergebnisse Insgesamt konnten 356 Patientinnen mit einem medianen prätherapeutischen BChE-Spiegel (IQR) von 6180 IU/l (Spanne 49907710 IU/l) in die Analyse einbezogen werden. Die medianen BChE-Serumspiegel waren in Patientinnen mit niedrigerem Body-Mass-Index (p < 0,001), fortgeschrittenem Tumorstadium (p = 0,04), schlechtem Therapieansprechen (p = 0,002) und dem Auftreten eines Rezidivs signifikant erniedrigt (p = 0,003). In uni- und multivariaten Überlebensanalysen waren niedrigere BChE-Spiegel (<6180 IU/l) mit kürzerem PFS (HR 1,8 [1,22,6]; p = 0,002), CSS (HR 2,2 [1,43,5], p < 0,001) und OS (HR 2,0 [1,42,9]; p < 0,001) assoziiert. Schlussfolgerung Erniedrigte prätherapeutische BChE-Spiegel sind mit fortgeschrittenem Tumorstadium und schlechterem Therapieansprechen assoziiert und eignen sich als unabhängige Prognoseparameter für kürzeres PFS, CSS und OS bei Zervixkarzinompatientinnen unter primärer (Chemo-)Radiotherapie.Background Deficiency in butyrylcholinesterase (BChE), a condition commonly noticed in liver damage, inflammation, and malnutrition, has previously been associated with impaired prognosis in different malignancies. The aim of the present study was to investigate the value of pretreatment serum BChE levels as a prognostic biomarker in patients with cervical cancer treated with primary (chemotherapy-[chemo-])radiation therapy. Methods We retrospectively evaluated data of a consecutive series of patients with cervical cancer treated with primary (chemo-)radiation therapy between 1998 and 2015. Pretreatment serum BChE levels were correlated with clinico-pathological parameters and response to treatment. Uni- and multivariate survival analyses were performed to assess the association between decreased serum BChE levels and progression-free (PFS), cancer-specific (CSS), and overall survival (OS). Results A total of 356 patients were eligible for inclusion into the present study. The median (IQR) pretreatment serum BChE level was 6180 (49907710) IU/l. Lower serum BChE levels were associated with lower BMI (p < 0.001), advanced tumor stage (p = 0.04), poor treatment response (p = 0.002), the occurrence of disease recurrence (p = 0.003), and the risk of death (p < 0.001). In uni- and multivariate analyses, low pretreatment serum BChE levels were independently associated with shorter PFS (HR 1.8 [1.22.6]; p = 0.002), CSS (HR 2.2 [1.43.5], p < 0.001), and OS (HR 2.0 [1.42.9]; p < 0.001). Conclusions Low pretreatment serum BChE levels are associated with advanced tumor stage and poor response to treatment, and serve as an independent prognostic biomarker for shorter PFS, CSS, and OS in patients with cervical cancer treated with primary (chemo-)radiation therapy.(VLID)509263

TRICIN: A Phase II Trial on the Efficacy of Topical TRIchloroacetic Acid in Patients with Cervical Intraepithelial Neoplasia

Data on non-surgical treatment approaching persistent cervical intraepithelial neoplasia (CIN) are scarce. Retrospective analysis suggest high efficacy of topical treatment with trichloroacetic acid (TCA). This prospective phase II study set out to investigate the efficacy of a single application of 85% TCA in the treatment of CIN I/II. Patients with CIN I/II were treated a single time with 85% TCA. After three and six months colposcopic, histologic, and HPV evaluation was performed. The primary endpoint was treatment efficacy defined as complete histologic remission six months after treatment. The secondary endpoint was HPV clearance six months after treatment. A total of 102 patients with CIN I/II were included into this trial. Complete histologic remission rates were 75.5% and 78.4% three and six months after TCA treatment, respectively. Clearance rates of HPV 16, 18 and other high risk types were 76.5%, 91.7%, 68.7% after six months, respectively. Side effects of TCA were mild and lasted usually less than 30 min. This is the first prospective trial reporting high histologic complete remission rates in patients with CIN I/II after a single 85% TCA treatment. In the future, TCA may represent an effective and feasible non-surgical treatment approach for CIN

Risk Reclassification of Patients with Endometrial Cancer Based on Tumor Molecular Profiling: First Real World Data

Recently, guidelines for endometrial cancer (EC) were released that guide treatment decisions according to the tumors’ molecular profiles. To date, no real-world data regarding the clinical feasibility of molecular profiling have been released. This retrospective, monocentric study investigated the clinical feasibility of molecular profiling and its potential impact on treatment decisions. Tumor specimens underwent molecular profiling (testing for genetic alterations, (immune-)histological examination of lymphovascular space invasion (LVSI), and L1CAM) as part of the clinical routine and were classified according to the European Society for Medical Oncology (ESMO) classification system and to an integrated molecular risk stratification. Shifts between risk groups and potential treatment alterations are described. A total of 60 cases were included, of which twelve were excluded (20%), and eight of the remaining 48 were not characterized (drop-out rate of 16.7%). Molecular profiling revealed 4, 6, 25, and 5 patients with DNA polymerase-epsilon mutation, microsatellite instability, no specific molecular profile, and TP53 mutation, respectively. Three patients had substantial LVSI, and four patients showed high L1CAM expression. Molecular profiling took a median of 18.5 days. Substantial shifts occurred between the classification systems: four patients were upstaged, and 19 patients were downstaged. Molecular profiling of EC specimens is feasible in a daily routine, and new risk classification systems will change treatment decisions substantially