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During the coronavirus disease 2019 (COVID-19) pandemic, patients with humoral immunodeficiency are at higher risk of developing chronic infection and having a negative outcome. Few data are available on therapeutic options for this population. This case report discusses the treatment of disease relapse with remdesivir and monoclonal antibodies in an adult patient with X-linked agammaglobulinaemia.

COVID-19 spread in two pandemic waves in Italy between 2020 and 2021. The aim of this study is to compare the first with the second COVID-19 wave, analyzing modifiable and non-modifiable factors and how these factors affected mortality in patients hospitalized in Internal Medicine wards. Consecutive patients with SARS-CoV-2 infection and dyspnea requiring O

Recently, case series studies on patients with SARS-CoV-2 infection reported an association between remdesivir (RDV) administration and incidental bradycardia. However, the phenomenon has not yet been described in detail. We conducted a retrospective case-control study to evaluate the occurrence of RDV-related bradycardia in patients hospitalized for SARS-CoV2 pneumoniae. We retrospectively evaluated 71 patients, hospitalized in six internal medicine wards of the Milan area, affected by mild-to-moderate COVID-19 who received RDV (RDV group) and 54 controls, matched for sex, age and disease severity on admission (CTR group). The mean heart rate value recorded during the first two days of hospitalization was considered as baseline heart rate (HRb). Heart rate values relative to the 5-days treatment and the 5-days post-treatment were extracted for RDV group, while heart rate values relative to 10 days of hospitalization were considered for the CTR group. ΔHR values were calculated as maximum HR drop versus HRb. Possible associations between ΔHR and clinical-demographic factors were assessed through regression analysis. The RDV group experienced a significantly higher incidence of bradycardia compared to the CTR group (56% vs 33%, OR 2.6, 95% CI 1.2-5.4, p value = 0.011). Moreover, the RDV group showed higher ΔHR values than the CTR group. The HR progressively decreased with daily administration of RDV, reaching the maximun drop on day six (-8.6±1.9 bpm). In RDV group, patients who experienced bradycardia had higher drop in HR, higher alanine aminotransferase (ALT) values at the baseline (bALT) and during the RDV administration period. ΔHR was positively associated with HRb (β = 0.772, p 0.001) and bALT (β = 0.245, p = 0.005). In conclusion, our results confirmed a significant association between RDV administration and development of bradycardia. This effect was proportional to baseline HR and was associated with higher levels of baseline ALT, suggesting a possible interaction between RDV liver metabolism and a vagally-mediated effect on HR due to increased availability of RDV metabolites.

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a highly pleiotropic ∼0.9-Mb inversion polymorphism and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung., Andre Franke and David Ellinghaus were supported by a grant from the German Federal Ministry of Education and Research (01KI20197), Andre Franke, David Ellinghaus and Frauke Degenhardt were supported by the Deutsche Forschungsgemeinschaft Cluster of Excellence “Precision Medicine in Chronic Inflammation” (EXC2167). David Ellinghaus was supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the Computational Life Sciences funding concept (CompLS grant 031L0165). David Ellinghaus, Karina Banasik and Søren Brunak acknowledge the Novo Nordisk Foundation (grant NNF14CC0001 and NNF17OC0027594). Tobias L. Lenz, Ana Teles and Onur Özer were funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project numbers 279645989; 433116033; 437857095. Mareike Wendorff and Hesham ElAbd are supported by the German Research Foundation (DFG) through the Research Training Group 1743, "Genes, Environment and Inflammation". This project was supported by a Covid-19 grant from the German Federal Ministry of Education and Research (BMBF; ID: 01KI20197). Luca Valenti received funding from: Ricerca Finalizzata Ministero della Salute RF2016-02364358, Italian Ministry of Health ""CV PREVITAL – strategie di prevenzione primaria cardiovascolare primaria nella popolazione italiana; The European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS- and for the project ""REVEAL""; Fondazione IRCCS Ca' Granda ""Ricerca corrente"", Fondazione Sviluppo Ca' Granda ""Liver-BIBLE"" (PR-0391), Fondazione IRCCS Ca' Granda ""5permille"" ""COVID-19 Biobank"" (RC100017A). Andrea Biondi was supported by the grant from Fondazione Cariplo to Fondazione Tettamanti: "Biobanking of Covid-19 patient samples to support national and international research (Covid-Bank). This research was partly funded by a MIUR grant to the Department of Medical Sciences, under the program "Dipartimenti di Eccellenza 2018–2022". This study makes use of data generated by the GCAT-Genomes for Life. Cohort study of the Genomes of Catalonia, Fundació IGTP. IGTP is part of the CERCA Program / Generalitat de Catalunya. GCAT is supported by Acción de Dinamización del ISCIIIMINECO and the Ministry of Health of the Generalitat of Catalunya (ADE 10/00026); the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR 529). Marta Marquié received research funding from ant PI19/00335 Acción Estratégica en Salud, integrated in the Spanish National RDI Plan and financed by ISCIIISubdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER-Una manera de hacer Europa")., Beatriz Cortes is supported by national grants PI18/01512. Xavier Farre is supported by VEIS project (001-P-001647) (cofunded by European Regional Development Fund (ERDF), “A way to build Europe”). Additional data included in this study was obtained in part by the COVICAT Study Group (Cohort Covid de Catalunya) supported by IsGlobal and IGTP, EIT COVID-19 Rapid Response activity 73A and SR20-01024 La Caixa Foundation. Antonio Julià and Sara Marsal were supported by the Spanish Ministry of Economy and Competitiveness (grant numbers: PSE-010000-2006-6 and IPT-010000-2010-36). Antonio Julià was also supported the by national grant PI17/00019 from the Acción Estratégica en Salud (ISCIII) and the FEDER. The Basque Biobank is a hospitalrelated platform that also involves all Osakidetza health centres, the Basque government's Department of Health and Onkologikoa, is operated by the Basque Foundation for Health Innovation and Research-BIOEF. Mario Cáceres received Grants BFU2016-77244-R and PID2019-107836RB-I00 funded by the Agencia Estatal de Investigación (AEI, Spain) and the European Regional Development Fund (FEDER, EU). Manuel Romero Gómez, Javier Ampuero Herrojo, Rocío Gallego Durán and Douglas Maya Miles are supported by the “Spanish Ministry of Economy, Innovation and Competition, the Instituto de Salud Carlos III” (PI19/01404, PI16/01842, PI19/00589, PI17/00535 and GLD19/00100), and by the Andalussian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018, COVID-Premed, COVID GWAs). The position held by Itziar de Rojas Salarich is funded by grant FI20/00215, PFIS Contratos Predoctorales de Formación en Investigación en Salud. Enrique Calderón's team is supported by CIBER of Epidemiology and Public Health (CIBERESP), "Instituto de Salud Carlos III". Jan Cato Holter reports grants from Research Council of Norway grant no 312780 during the conduct of the study. Dr. Solligård: reports grants from Research Council of Norway grant no 312769. The BioMaterialBank Nord is supported by the German Center for Lung Research (DZL), Airway Research Center North (ARCN). The BioMaterialBank Nord is member of popgen 2.0 network (P2N). Philipp Koehler has received non-financial scientific grants from Miltenyi Biotec GmbH, Bergisch Gladbach, Germany, and the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany. He is supported by the German Federal Ministry of Education and Research (BMBF)., Oliver A. Cornely is supported by the German Federal Ministry of Research and Education and is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy – CECAD, EXC 2030 – 390661388. The COMRI cohort is funded by Technical University of Munich, Munich, Germany. Genotyping was performed by the Genotyping laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki. This work was supported by grants of the Rolf M. Schwiete Stiftung, the Saarland University, BMBF and The States of Saarland and Lower Saxony. Kerstin U. Ludwig is supported by the German Research Foundation (DFG, LU-1944/3-1). Genotyping for the BoSCO study is funded by the Institute of Human Genetics, University Hospital Bonn. Frank Hanses was supported by the Bavarian State Ministry for Science and Arts. Part of the genotyping was supported by a grant to Alfredo Ramirez from the German Federal Ministry of Education and Research (BMBF, grant: 01ED1619A, European Alzheimer DNA BioBank, EADB) within the context of the EU Joint Programme – Neurodegenerative Disease Research (JPND). Additional funding was derived from the German Research Foundation (DFG) grant: RA 1971/6-1 to Alfredo Ramirez. Philip Rosenstiel is supported by the DFG (CCGA Sequencing Centre and DFG ExC2167 PMI and by SH state funds for COVID19 research). Florian Tran is supported by the Clinician Scientist Program of the Deutsche Forschungsgemeinschaft Cluster of Excellence “Precision Medicine in Chronic Inflammation” (EXC2167). Christoph Lange and Jan Heyckendorf are supported by the German Center for Infection Research (DZIF). Thorsen Brenner, Marc M Berger, Oliver Witzke und Anke Hinney are supported by the Stiftung Universitätsmedizin Essen. Marialbert Acosta-Herrera was supported by Juan de la Cierva Incorporacion program, grant IJC2018-035131-I funded by MCIN/AEI/10.13039/501100011033. Eva C Schulte is supported by the Deutsche Forschungsgemeinschaft (DFG; SCHU 2419/2-1).

Aims To assess the appropriateness of oral anticoagulant (OAC) prescription and its associated factors in acutely hospitalized elderly patients. Methods Data were obtained from the prospective phase of SIM-AF (SIMulation-based technologies to improve the appropriate use of oral anticoagulants in hospitalized elderly patients with Atrial Fibrillation) randomized controlled trial, aimed to test whether an educational intervention improved OAC prescription, compared to current clinical practice, in internal medicine wards. In this secondary analysis, appropriateness of OAC prescription was assessed at hospital admission and discharge. Results For 246 patients, no significant differences were found between arms (odds ratio 1.38, 95% confidence interval [CI] 0.84-2.28) in terms of appropriateness of OAC prescription. Globally, 92 patients (37.4%, 95% CI = 31.6-43.6%) were inappropriately prescribed or not prescribed at hospital discharge. Among 51 patients inappropriately prescribed, 82% showed errors on dosage, being mainly under-dosed (n = 29, 56.9%), and among 41 inappropriately not prescribed, 98% were taking an antiplatelet drug. Factors independently associated with a lower probability of appropriateness at discharge were those related to a higher risk of bleeding (older age, higher levels of aspartate aminotransferase, history of falls, alcohol consumption) and antiplatelet prescription at admission. The prescription of OACs at admission was the strongest predictor of appropriateness at discharge (odds ratio = 7.43, 95% CI = 4.04-13.73). Conclusions A high proportion of hospitalized older patients with AF remains inappropriately prescribed or nonprescribed with OACs. The management of these patients at hospital admission is the strongest predictor of prescription appropriateness at discharge.

Aims: Although oral anticoagulants (OACs) are effective in preventing stroke in older people with atrial fibrillation (AF), they are often underused in this particularly high-risk population. The aim of the present study was to assess the appropriateness of OAC prescription and its associated factors in hospitalized patients aged 65years or older. Methods: Data were obtained from the retrospective phase of Simulation-based Technologies to Improve the Appropriate Use of Oral Anticoagulants in Hospitalized Elderly Patients With Atrial Fibrillation (SIM-AF) study, held in 32 Italian internal medicine and geriatric wards. The appropriateness of OAC prescription was assessed, grouping patients in those who were and were not prescribed OACs at hospital discharge. Multivariable logistic regression was used to establish factors independently associated with the appropriateness of OAC prescription. Results: A total of 328 patients were included in the retrospective phase of the study. Of these, almost 44% (N = 143) were inappropriately prescribed OACs, being mainly underprescribed or prescribed an inappropriate antithrombotic drug (N = 88). Among the patients prescribed OACs (N=221), errors in the prescribed doses were the most frequent cause of inappropriate use (N=55). Factors associated with a higher degree of patient frailty were inversely associated with the appropriateness of OAC prescription. Conclusions: In hospitalized older patients with AF, there is still a high prevalence of inappropriate OAC prescribing. Characteristics usually related to frailty are associated with the inappropriate prescribing. These findings point to the need for targeted interventions designed for internists and geriatricians, aimed at improving the appropriate prescribing of OACs in this complex and high-risk population.

Anemia is a common finding in elderly individuals. Several studies have shown a strong relationship between anemia, morbidity and mortality, suggesting anemia as a significant independent predictor of adverse outcome in elderly hospitalized patients. The pathophisiology of anemia in the elderly is not yet completely understood. Several mechanisms are involved. We investigated the prevalence of anemia in a cohort of 193 elderly patients admitted to the Internal Medicine Ward of Ca'Granda Policlinico Hospital along 6 months, and its relationship to comorbidities and to the length of hospitalization. Anemia was classified according to the WHO criteria. The majority of patients (48 %) had a mildmoderate, normocytic anemia; severe anemia was found in 8 out of 92 anemic patients. In a subgroup of patients erythropoietin was tested and resulted statistically higher if compared to non-anemic controls (p = 0.003). Considering the most common cause of anemia, nutritional deficiency, chronic renal disease and anemia of chronic disease were found respectively in 36, 15 and 25 % of cases. Unexplained anemia was diagnosed in 24 % of patients, according to the literature. Anemia was independently associated with increased length of hospital stay. Our study confirmed a high prevalence of anemia in elderly patients, and its association with a higher number of comorbidities and a longer stay. A correct clinical approach to anemia in elderly hospitalized patients is essential, considering its negative impact on patients' quality of life, and its social burden in term of healthcare needs and costs.

Dr. Spinelli We report a case of a 75-year-old woman with Child-Pugh Class 7 B HCV cirrhosis, admitted to our hospital for high fever (38.5 C), chills and fatigue. These symptoms started approximately 1 month prior, and progressively worsened. At home, she was treated with levofloxacin without benefit. She reported anorexia and loss of weight of 4 kg. A recent upper-digestive endoscopy (EGDS) showed fine caliber esophageal varices; the ultrasonography of the abdomen revealed signs of chronic liver disease and splenomegaly. The patient was alert and oriented, even if a bit slackened. On physical examination, she had no sign of meningismus and no jaundice. Vital signs: body temperature 37.5 C, heart rate 72 beats/min, blood pressure of 100/60 mmHg. Oxygen saturation by pulse oximetry was 95 % on room air. Body mass index (BMI): 19.9. Cranial nerve examination was normal. She had minimal ascites and hepatomegaly. There was edema of grade-2 in the lower extremity bilaterally. The rest of the general body examination was normal. Blood laboratory tests revealed a sever iron deficiency anaemia (haemoglobin 7.6 g/dl), increased transaminases, low pseudocholinesterase and hypoalbuminemia. Inflammation indices were negative. She was transfused with several red blood cells (RBC) units, and was initially treated with ceftriaxone without benefit. She was initially supported with a balanced hypoproteinemic low-sodium oral diet. Because of worsening deterioration of the general condition, she was also treated with parenteral nutrition (aminoacid solution, vitamins, glucose, electrolytes, lipids) for a total caloric contribution of 1,320 kcal/daily.

Case presentationDr. Giovanna Squiccimarro In December 2009, a previ-ously healthy 48-year-old man was admitted because ofhypertensive crisis and bilateral diffuse ground-glassshadows on the chest X-ray study.He presented at the Emergency Department (ED) com-plaining of worsening dyspnea.The respiratory rate was 35 breaths/min and SpO2 93%at pulse oximeter. His blood pressure (BP) was 220/120mmHg and the heart rate 120 beats/min.He was overweight, afebrile and diaphoretic. He had ahistory of alcohol and tobacco abuse (more than 20 ciga-rettes/day). He denied use of any medications, and reportedthat mild dyspnea and fever (TA 39 C) acutely began3 weeks prior. The fever resolved without any therapy in afew days but a mild dyspnea persisted.Ten days prior to admission, dyspnea was still presentand an isolated hemoptysis occurred.Normal lung breath sounds and a 3/6 heart systolicmurmur were heard on the examination. The electrocar-diogram (EKG) showed sinus tachycardia, right bundle-branch block and S1–Q3 pattern.Arterial blood gas (ABG) analysis while breathing roomair showed pH 7.47, PaO2 57 mmHg, pCO2 33 mmHg,HCO3- 25.4 mmol/L. Laboratory tests were normalexcept for WBC count 10,200/mmc (N = 80%), C-RP1.31 mg/dL (normal range\0.5), creatinine 1.4 mg/dL,K

This case report describes the previously-unreported clinical course of a patient with a so-called incomplete systemic lupus erythematosus (SLE), i.e. symptoms related to one organ system only, together with the presence of ANA. He had an indolent course initially and developed, 6 months after the first symptoms, a severe disease with rapid appearance of major and unusual manifestations. The possibility of fast progression and a grave course of an incomplete SLE should be kept in mind. This report is meant to heighten awareness of such an atypical presentation so that prompt and aggressive immunosuppressive therapy may be instituted.

The study compares the ability of the PSI (pneumonia severity index), CURB-65 (confusion, urea >7 mol·L(-1), respiratory rate ≥ 30 breaths·min(-1), blood pressure

Invasive fungal rhinosinusitis (IFR) is a life-threatening infection. Its onset is subtle and a late diagnosis leads to severe complications. Death may occur within a few weeks notwithstanding treatment. We describe a comprehensive pre- and post-operative approach to care for haematological patients with IFR. Five haematological patients with IFR were treated with systemic antifungal therapy and endoscopic surgical debridement of infected tissues, followed by amphotericin-B directly instilled in the sinuses by a new type of ethmoidal drainage. The IFR remitted in all cases; after 32 months of follow-up, three patients are still alive, and two have died of other causes. Two of the patients who experienced IFR progression to the brain at the IFR onset are still alive. The pharmacological and surgical approach with the post-operative local therapy by a new ethmoidal drainage system could support radical antifungal sinus treatment, thus improving the overall survival.

We studied Leu 7 + cell distribution and natural killer (NK) activity in the peripheral blood of six patients who had peripheral neuropathy and monoclonal IgM protein directed against myelin-associated glycoprotein (anti-MAG IgM). We did not find any difference between patients and control subjects (healthy or polyneuropathic, some with IgM monoclonal paraprotein but without anti-MAG activity). The presence of autologous sera did not interfere with these results. We noted an increase in Leu 11 + cell percentages after pre-incubation of the patient cells with autologous sera but the phenotypes of cells from control subjects did not changes after incubation with autologous or patient sera.