A single-dose strategy for immunization with live attenuated vaccines is an effective option before treatment initiation in multiple sclerosis patients.

BACKGROUND: Mumps-Measles-Rubella (MMR) and Varicella zoster vaccines (VAR) are live attenuated vaccines, usually administered in a two-dose scheme at least 4 weeks apart. However, single-dose immunization schemes may also be effective and can reduce delays in immunosuppressive treatment initiation in patients with multiple sclerosis (pwMS) who need to be immunized. OBJECTIVES: To evaluate the immunogenicity of a single-dose attempt (SDA) versus the standard immunization scheme (SIS) with VAR and/or MMR in pwMS. METHODS: Retrospective observational study in pwMS vaccinated against VAR and/or MMR. We compared seroprotection rates and antibody geometric mean titers (GMTs) between the two strategies. RESULTS: Ninety-six patients were included. Thirty-one patients received VAR and 67 MMR. In the SDA group, the seroprotection rate was 66.7% (95% confidence interval (CI): 53.3-78.3) versus 97.2% (95% CI: 85.5-99.9) in the SIS (p < 0.001). For the seroprotected patients, GMTs were similar for both schemes. CONCLUSION: An SDA of VAR and/or MMR vaccines could be sufficient to protect almost two-thirds of patients. Testing immunogenicity after a single dose of VZ and/or MMR could be included in routine clinical practice to achieve rapid immunization.

Kinetics of cellular and humoral immunogenicity and effectiveness of SARS-CoV-2 booster vaccination in hematologic neoplasms.

Data on the effect of booster SARS-CoV-2 vaccination are mainly focused on humoral immunogenicity, while the kinetics of vaccine-induced cellular response and its correlation with effectiveness in hematologic patients are less explored. Our aim was to evaluate the longitudinal cellular and humoral immunogenicity induced by two and three doses of the mRNA-1273 SARS-CoV-2 vaccine in 270 patients with hematologic malignancies, and its relationship with the severity of breakthrough SARS-CoV-2 infection. Results indicate that at 23 weeks after the second dose, the seroconversion rate declined from 68.5% to 59.3%, with a reduction in median anti-S titers from 1577 to 456 BAU/mL, mainly in patients over 65 years of age or chronic lymphocytic leukemia (CLL) patients undergoing active therapy. Cellular immunogenicity, however, remained positive in 84.4% of cases. A third vaccine dose seroconverted 42.7% (41/96) and triggered cellular response in 36.7% (11/30) of previously negative patients. Notably, only 7.2% (15/209) of patients failed to develop both humoral and cellular response. Active therapy, anti-CD20 antibodies, lymphopenia, hypogammaglobulinemia, and low CD19+ cell count were associated with poor humoral response, while active disease, GvHD immunosuppressive therapy, lymphopenia, and low CD3+ , CD4+ , CD56+ cell count determined an impaired cellular response. After 13.8 months of follow-up, the incidence of SARS-CoV-2 infection was 24.8% (67/270), including 6 (9%) severe/critical cases associated with a weaker cellular (median interferon gamma (IFN-γ) 0.19 vs. 0.35 IU/mL) and humoral response (median anti-S titer <4.81 vs. 788 BAU/mL) than asymptomatic/mild cases. In conclusion, SARS-CoV-2 booster vaccination improves humoral response and COVID-19 severity is associated with impaired vaccine-induced immunogenicity.

Recommendations for screening, monitoring, prevention, and prophylaxis of infections in adult and pediatric patients receiving CAR T-cell therapy: a position paper.

Chimeric antigen receptor (CAR) T-cell therapy is one of the most promising emerging treatments for B-cell malignancies. Recently, two CAR T-cell products (axicabtagene ciloleucel and tisagenlecleucel) have been approved for patients with aggressive B-cell lymphoma and acute lymphoblastic leukemia; many other CAR-T constructs are in research for both hematological and non-hematological diseases. Most of the patients receiving CAR-T therapy will develop fever at some point after infusion, mainly due to cytokine release syndrome (CRS). The onset of CRS is often indistinguishable from an infection, which makes management of these patients challenging. In addition to the lymphodepleting chemotherapy and CAR T cells, the treatment of complications with corticosteroids and/or tocilizumab increases the risk of infection in these patients. Data regarding incidence, risk factors and prevention of infections in patients receiving CAR-T cell therapy are scarce. To assist in patient care, a multidisciplinary team from hospitals designated by the Spanish Ministry of Health to perform CAR-T therapy prepared these recommendations. We reviewed the literature on the incidence, risk factors, and management of infections in adult and pediatric patients receiving CAR-T cell treatment. Recommendations cover different areas: monitoring and treatment of hypogammaglobulinemia, prevention, prophylaxis, and management of bacterial, viral, and fungal infections as well as vaccination prior and after CAR-T cell therapy.

Asymptomatic SARS-CoV-2 Infection in Nursing Homes, Barcelona, Spain, April 2020.

During the coronavirus disease pandemic in Spain, from April 10-24, 2020, a total of 5,869 persons were screened for severe acute respiratory syndrome coronavirus 2 at nursing homes. Among residents, 768 (23.9%) tested positive; among staff, 403 (15.2%). Of those testing positive, 69.7% of residents and 55.8% of staff were asymptomatic.

Multidisciplinary, evidence-based consensus guidelines for human papillomavirus (HPV) vaccination in high-risk populations, Spain, 2016.

INTRODUCTION: Although human papillomavirus (HPV) routine vaccination programmes have been implemented around the world and recommendations have been expanded to include other high-risk individuals, current recommendations often differ between countries in Europe, as well as worldwide. AIM: To find and summarise the best available evidence of HPV vaccination in high-risk patients aiding clinicians and public health workers in the day-to-day vaccine decisions relating to HPV in Spain. METHODS: We conducted a systematic review of the immunogenicity, safety and efficacy/effectiveness of HPV vaccination in high-risk populations between January 2006 and June 2016. HPV vaccination recommendations were established with levels of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: A strong recommendation about HPV vaccination was made in the following groups: HIV infected patients aged 9-26 years; men who have sex with men aged 9-26 years; women with precancerous cervical lesions; patients with congenital bone marrow failure syndrome; women who have received a solid organ transplant or hematopoietic stem cell transplantation aged 9-26 years; and patients diagnosed with recurrent respiratory papillomatosis. CONCLUSIONS: Data concerning non-routine HPV vaccination in populations with a high risk of HPV infection and associated lesions were scarce. We have developed a document to evaluate and establish evidence-based guidelines on HPV vaccination in high-risk populations in Spain, based on best available scientific evidence.

The diagnostic work-up of cancer-associated myositis.

PURPOSE OF REVIEW: Despite the well-recognized association between malignancy and myositis, definite data indicating the best strategy for diagnosing cancer in myositis patients is lacking. In this article, we review the data on cancer screening in patients with myositis, and propose an algorithm for this purpose based on recently published data. RECENT FINDINGS: Evidence has recently emerged supporting blind screening in patients with certain myositis phenotypes. In addition to the clinical examination, imaging techniques such as PET/computed tomography scanning and whole-body MRI, and determination of the autoantibody profile beyond anti-TIF1γ antibody, the well known cancer biomarker in dermatomyositis, will help the clinician face this complex clinical situation. Molecules related to the checkpoint inhibitor pathway, specifically soluble programmed death 1, may also have a role in the diagnostic work-up of cancer in myositis. In the future, blood tests analysing circulating DNA will certainly help in detecting patients with cancer-associated myositis (CAM). SUMMARY: A step forward has been achieved in the pathway to establish optimal cancer screening for myositis patients. International consensus guidelines for an effective diagnostic work-up of CAM are in progress and will be of paramount importance to improving the outcome in these patients.

Immunogenicity of hepatitis B vaccine in patients with inflammatory bowel disease and the benefits of revaccination.

BACKGROUND AND AIM: The vaccination against hepatitis B virus (HBV) is recommended in patients with inflammatory bowel disease (IBD). However, the response to this vaccine seems to be lower in IBD patients than in the general population. This study aims to evaluate the immunogenicity of the HBV vaccine in a cohort of patients with IBD, to associate factors with the response and to analyze the effects of a second schedule vaccination. METHODS: We conducted a retrospective cohort study of adults with IBD, susceptible to HBV infection. All patients received a three-dose standard schedule of HBV vaccine. Non-responders were revaccinated with a second three-dose standard schedule. Adequate immunity to HBV was defined as antibodies against hepatitis B surface antigen (anti-HBs) ≥ 10 mIU/mL. Age, comorbidities, treatment, and other variables were collected. RESULTS: One hundred seventy-two patients were included and received the first HBV vaccine schedule. Eighty-seven developed anti-HBs ≥ 10 mIU/mL (50.6%; 95% confidence interval [CI]: 42.9-58.3). From the non-responders, 53 were revaccinated and 28 showed an adequate serological response (52.8%; 95% CI: 38.6-66.7). Age older than 55 years (OR: 3.6; 95% CI: 1.3-10.2) and comorbidities (OR: 2.8; 95% CI: 1.1-7.1) were associated with suboptimal response. In the multivariate analysis, only age was a predictor of non-response (age higher than 55 years; OR: 3.9; 95% CI: 1.3-11.9) CONCLUSION: The response rate to the HBV vaccine is lower in patients with IBD compared with the general population, especially in those older than 55 years. Revaccination improved response rate by 50%.

[Carbapenem antibiotics in hospitalised paediatric patients. Adherence to a therapeutic protocol]. / Uso de antibióticos carbapenémicos en enfermos pediátricos hospitalizados. Adecuación de su prescripción a un protocolo terapéutico.

OBJECTIVE: To describe the use of carbapenems in children hospitalised outside intensive care and onco-haematology units, and assess adherence to a therapeutic protocol. PATIENTS AND METHODS: A retrospective observational study was conducted on the use of carbapenems between January 2009 and December 2010. The study included children with a community-acquired infectious disease or a health care-associated infectious disease, and who were admitted to paediatric areas of the Vall d'Hebron University Hospital (Barcelona, Spain), other than intensive care, neonatology and onco-haematology units. Clinical data were collected and antibiotic consumption data were provided by the Pharmacy Department. RESULTS: A total of 51 episodes fulfilled the inclusion criteria. Carbapenem as initial empirical treatment was indicated in 31.4%, and applied as rescue therapy in the remainder. The instructions of the protocol were adhered to in 70.6% of the empirical and 87.5% of the targeted prescriptions (77.6% overall). A better match was found for empirical carbapenem in patients with a previous admission or underlying condition. Factors such as diagnosis, age or antibiotic use prior to admission did not affect the empirical indication of carbapenem. CONCLUSIONS: The establishment of a treatment protocol with carbapenem indications in our centre since 2007 has yielded significantly better results on the appropriateness of the prescription than those obtained in other studies.

Vaccine Safety and Immunogenicity in Patients With Multiple Sclerosis Treated With Natalizumab.

Importance: Vaccination in patients with highly active multiple sclerosis (MS) requiring prompt treatment initiation may result in impaired vaccine responses and/or treatment delay. Objective: To assess the immunogenicity and safety of inactivated vaccines administered during natalizumab treatment. Design, Setting, and Participants: This self-controlled, prospective cohort study followed adult patients with MS from 1 study center in Spain from September 2016 to February 2022. Eligible participants included adults with MS who completed immunization for hepatitis B virus (HBV), hepatitis A virus (HAV), and COVID-19 during natalizumab therapy. Data analysis was conducted from November 2022 to February 2023. Exposures: Patients were categorized according to their time receiving natalizumab treatment at the time of vaccine administration as short-term (≤1 year) or long-term (>1 year). Main Outcomes and Measures: Demographic, clinical, and radiological characteristics were collected during the year before vaccination (prevaccination period) and the year after vaccination (postvaccination period). Seroprotection rates and postvaccination immunoglobulin G titers were determined for each vaccine within both periods. Additionally, differences in annualized relapse rate (ARR), new T2 lesions (NT2L), Expanded Disability Status Scale (EDSS) scores, and John Cunningham virus (JCV) serostatus between the 2 periods were assessed. Results: Sixty patients with MS (mean [SD] age, 43.2 [9.4] years; 44 female [73.3%]; 16 male [26.7%]; mean [SD] disease duration, 17.0 [8.7] years) completed HBV, HAV, and mRNA COVID-19 immunization during natalizumab treatment, with 12 patients in the short-term group and 48 patients in the long-term group. The global seroprotection rate was 93% (95% CI, 86%-98%), with individual vaccine rates of 92% for HAV (95% CI, 73%-99%), 93% for HBV (95% CI, 76%-99%), and 100% for the COVID-19 messenger RNA vaccine (95% CI, 84%-100%). Between the prevaccination and postvaccination periods there was a significant reduction in the mean (SD) ARR (0.28 [0.66] vs 0.01 [0.12]; P = .004) and median (IQR) NT2L (5.00 [2.00-10.00] vs 0.81 [0.00-0.50]; P = .01). No changes in disability accumulation were detected (median [IQR] EDSS score 3.5 [2.0-6.0] vs 3.5 [2.0-6.0]; P = .62). No differences in safety and immunogenicity were observed for all vaccines concerning the duration of natalizumab treatment. Conclusions and Relevance: The findings of this cohort study suggest that immunization with inactivated vaccines during natalizumab therapy was both safe and immunogenic, regardless of the treatment duration. Natalizumab may be a valuable option for proper immunization, averting treatment delays in patients with highly active MS; however, this strategy needs to be formally evaluated.

Calcineurin inhibitors in a cohort of patients with antisynthetase-associated interstitial lung disease.

OBJECTIVES: The aim of this paper is to assess the effect of calcineurin inhibitors (tacrolimus or cyclosporine) for treating patients with interstitial lung disease (ILD) associated with antisynthetase autoantibodies. METHODS: Sixty patients with antisynthetase autoantibodies were identified in our myositis cohort of 179 patients. The medical records of 15 patients with antisynthetase autoantibody-associated ILD treated with tacrolimus/cyclosporine (11 for refractory disease and 4 as first-line therapy) between 1980 and 2011 were retrospectively reviewed. Serial pulmonary function tests were used to assess the clinical response. Qualitative data are presented as a number and percentage, and quantitative data as the median and interquartile range (IQR). RESULTS: Patients were classified as having probable or definite idiopathic inflammatory myopathy (8 dermatomyositis and 4 polymyositis), and pure interstitial lung disease (3 cases). The 15 patients had received tacrolimus/cyclosporine for an average of 19 (IQR 14-30) months. Median age at onset of ILD was 42.3 (IQR 32.4-56.8) years and median duration of lung disease before administration of calcineurin inhibitors was 11 (IQR: 5-49) months. Median duration of follow-up was 24 (IQR 12-32) months. Thirteen patients had anti-histidyl-transfer RNA synthetase autoantibody (anti-Jo-1) and two had anti-alanyl-transfer RNA synthetase autoantibody (anti-PL-12). A more than 10% increase in FVC or stabilisation was observed in 13 (87%; 95%CI 56-98) patients who received calcineurin inhibitors (9 [81%] refractory cases and 4 [100%] as first-line therapy). CONCLUSIONS: Calcineurin inhibitors seem to be a good therapeutic option for managing ILD associated with antisynthetase autoantibodies, not only in refractory cases, but also as first-line treatment.

Usefulness of anti-p155 autoantibody for diagnosing cancer-associated dermatomyositis: a systematic review and meta-analysis.

OBJECTIVE: Anti-p155 autoantibody, which was recently described in adult patients with dermatomyositis (DM), seems to be associated with cancer in this population. We performed a systematic review and meta-analysis to ascertain the accuracy of anti-p155 testing for the diagnosis of cancer-associated myositis. METHODS: We searched relevant databases, with no restrictions on study design or language, for original studies that included adult patients with probable/definite DM or amyopathic DM who were evaluated for neoplasm and anti-p155 status. Pooled sensitivity and specificity were calculated using a bivariate model. We computed the diagnostic odds ratio (OR), likelihood ratios (LRs) for positive and negative test results, positive and negative predictive values, and the summary receiver operating characteristic (SROC) curve. Statistical heterogeneity between studies was assessed using the I(2) statistic, and 95% confidence intervals (95% CIs) were computed for the parameters studied. RESULTS: Six studies including a total of 312 adult patients with DM were selected. The pooled sensitivity of anti-p155 for diagnosing cancer-associated DM was 78% (95% CI 45-94%), and specificity was 89% (95% CI 82-93%). The diagnostic OR was 27.26 (95% CI 6.59-112.82), and LRs for positive and negative test results were 6.79 (95% CI 4.11-11.23) and 0.25 (95% CI 0.08-0.76), respectively. Heterogeneity was substantial except with regard to the LR for a positive test result. The area under the SROC curve was 0.91 (95% CI 0.88-0.93). Taking the pooled prevalence of 17% as pretest probability, anti-p155 had a positive predictive value of 58% and a negative predictive value of 95%. CONCLUSION: Our findings indicate that anti-p155 autoantibody determination is useful for diagnosing cancer-associated myositis and guiding disease management.

Enhanced safety surveillance of GSK's quadrivalent seasonal influenza vaccine in Germany and Spain (2021/2022 season) using an electronic patient-reported outcome system for vaccine safety remote monitoring.

BACKGROUND: Seasonal influenza epidemics are managed through vaccination each winter in the European Union, to prevent infections, complications, and deaths. As circulating virus strains vary unpredictably, vaccines are reformulated annually, and their safety monitored rapidly and continuously at the start of each season, following European Medicines Agency guidelines.Seasonal influenza epidemics are managed through vaccination each winter in the European Union, to prevent infections, complications, and deaths. As circulating virus strains vary unpredictably, vaccines are reformulated annually, and their safety monitored rapidly and continuously at the start of each season, following European Medicines Agency guidelines. METHODS: This enhanced safety surveillance study assessed pre-specified and other adverse events (AEs) occurring within 7 days of GSK's inactivated quadrivalent seasonal influenza vaccine (IIV4) in children and adults in Spain and Germany. As the study was conducted during the COVID-19 pandemic (2021/2022 season), data were collected electronically, using a web portal or call center. RESULTS: Safety was assessed in 737 participants (median age 49 and 9 years in Germany and Spain, respectively, 19.3% with a chronic medical condition). After Dose 1 and Dose 2, respectively, 332 (45.1%) and 5 (26.3%) participants reported at least one AE, primarily pre-specified AEs. The most common AEs after Dose 1 (adults and children) were injection site pain, swelling or erythema, headache, and fatigue. After Dose 2 (in children), the most common AEs were injection site pain, rhinorrhea, fatigue, and decreased appetite. No new or unexpected safety issues were identified. CONCLUSION: This study supports and confirms the safety profile of GSK's IIV4 in all age groups with a vaccine indication. The new electronic safety reporting method (with response rates of 75.4% following Dose 1 and 100% following Dose 2) provides an alternative for future studies to reduce the burden on sites or in case site visits are not feasible.

Suspected case of monkeypox reinfection versus reactivation in a immunocompetent patient, Barcelona, 2022.

Vaccines against smallpox are known to have cross-protective activity against monkeypox, and smallpox and monkeypox infections are believed to generate permanent immunity. Nevertheless, there are scarce data about the possibility of reinfection or reactivation. Recently, a case of apparent monkeypox reinfection has been reported. We present a suspected case of second episode of monkeypox in a healthy and previously vaccinated man, with a confirmed primary monkeypox infection occurring three months before the second confirmed presentation.

Influenza Vaccine Effectiveness against Hospitalization, Season 2021/22: A Test-Negative Design Study in Barcelona.

BACKGROUND: Vaccination is considered the most effective measure for preventing influenza and its complications. The influenza vaccine effectiveness (IVE) varies annually due to the evolution of influenza viruses and the update of vaccine composition. Assessing the IVE is crucial to facilitate decision making in public health policies. AIM: to estimate the IVE against hospitalization and its determinants in the 2021/22 season in a Spanish tertiary hospital. METHODS: We conducted a prospective observational test-negative design study within the Development of Robust and Innovative Vaccine Effectiveness (DRIVE) project. Hospitalized patients with severe acute respiratory infection (SARI) and an available influenza reverse transcription polymerase chain reaction (RT-PCR) were selected and classified as cases (positive influenza RT-PCR) or controls (negative influenza RT-PCR). Vaccine information was obtained from electronic clinical records shared by public healthcare providers. Information about potential confounders was obtained from hospital clinical registries. The IVE was calculated by subtracting the ratio of the odds of vaccination in cases and controls from one, as a percentage (IVE = (1 - odds ratio (OR)) × 100). Multivariate IVE estimates were calculated using logistic regression. RESULTS: In total, 260 severe acute respiratory infections (SARI) were identified, of which 34 were positive for influenza, and all were subtype A(H3N2). Fifty-three percent were vaccinated. Adjusted IVE against hospitalization was 26.4% (95% CI -69% to 112%). IVE determinants could not be explored due to sample size limitations. CONCLUSION: Our data revealed non-significant moderate vaccine effectiveness against hospitalization for the 2021/2022 season.

Reactogenicity to the mRNA-1273 Booster According to Previous mRNA COVID-19 Vaccination.

The objective of this study was to assess the local and systemic adverse reactions after the administration of a COVID-19 mRNA-1273 booster between December 2021 and February 2022 by comparing the type of mRNA vaccine used as primary series (mRNA-1273 or BNT162b2) and homologous versus heterologous booster in health care workers (HCW). A cross-sectional study was performed in HCW at a tertiary hospital in Barcelona, Spain. A total of 17% of booster recipients responded to the questionnaire. The frequency of reactogenicity after the mRNA-1273 booster (88.5%) was similar to the mRNA-1273 primary doses (85.8%), and higher than the BNT162b2 primary doses (71.1%). The reactogenicity was similar after receiving a heterologous booster compared to a homologous booster (88.0% vs. 90.2%, p = 0.3), and no statistically significant differences were identified in any local or systemic reactions. A higher frequency of medical leave was identified in the homologous booster dose group vs. the heterologous booster dose group (AOR 1.45; 95% CI: 1.00-2.07; p = 0.045). Our findings could be helpful in improving vaccine confidence toward heterologous combinations in the general population and in health care workers.

Exposing and Overcoming Limitations of Clinical Laboratory Tests in COVID-19 by Adding Immunological Parameters; A Retrospective Cohort Analysis and Pilot Study.

Background: Two years since the onset of the COVID-19 pandemic no predictive algorithm has been generally adopted for clinical management and in most algorithms the contribution of laboratory variables is limited. Objectives: To measure the predictive performance of currently used clinical laboratory tests alone or combined with clinical variables and explore the predictive power of immunological tests adequate for clinical laboratories. Methods: Data from 2,600 COVID-19 patients of the first wave of the pandemic in the Barcelona area (exploratory cohort of 1,579, validation cohorts of 598 and 423 patients) including clinical parameters and laboratory tests were retrospectively collected. 28-day survival and maximal severity were the main outcomes considered in the multiparametric classical and machine learning statistical analysis. A pilot study was conducted in two subgroups (n=74 and n=41) measuring 17 cytokines and 27 lymphocyte phenotypes respectively. Findings: 1) Despite a strong association of clinical and laboratory variables with the outcomes in classical pairwise analysis, the contribution of laboratory tests to the combined prediction power was limited by redundancy. Laboratory variables reflected only two types of processes: inflammation and organ damage but none reflected the immune response, one major determinant of prognosis. 2) Eight of the thirty variables: age, comorbidity index, oxygen saturation to fraction of inspired oxygen ratio, neutrophil-lymphocyte ratio, C-reactive protein, aspartate aminotransferase/alanine aminotransferase ratio, fibrinogen, and glomerular filtration rate captured most of the combined statistical predictive power. 3) The interpretation of clinical and laboratory variables was moderately improved by grouping them in two categories i.e., inflammation related biomarkers and organ damage related biomarkers; Age and organ damage-related biomarker tests were the best predictors of survival, and inflammatory-related ones were the best predictors of severity. 4) The pilot study identified immunological tests (CXCL10, IL-6, IL-1RA and CCL2), that performed better than most currently used laboratory tests. Conclusions: Laboratory tests for clinical management of COVID 19 patients are valuable but limited predictors due to redundancy; this limitation could be overcome by adding immunological tests with independent predictive power. Understanding the limitations of tests in use would improve their interpretation and simplify clinical management but a systematic search for better immunological biomarkers is urgent and feasible.

Brand-Specific Enhanced Safety Surveillance Study of GSK's Quadrivalent Seasonal Influenza Vaccine, Conducted During the COVID-19 Pandemic, in Belgium, Germany and Spain, for the 2020/21 Season.

INTRODUCTION: Seasonal influenza poses a major public health burden worldwide. Influenza vaccines, updated yearly to match circulating strains based on World Health Organization (WHO) recommendations, are the cornerstone of prevention and require regular monitoring. The COVID-19 pandemic is expected to cause logistical, site access and medical staff constraints and could affect the safety profile of influenza vaccines. METHODS: Following European Medicines Agency guidance, an enhanced safety surveillance (ESS) study assessed the frequency and severity of predefined and other adverse events (AEs) occurring within 7 days of receiving GSK's inactivated quadrivalent seasonal influenza vaccine (IIV4), in Belgium, Germany and Spain in 2020/21, using adverse drug reaction (ADR) cards. RESULTS: During the 2020/21 influenza season, 1054 participants vaccinated with GSK's IIV4 were enrolled (all adults in Belgium and Germany, 30% adults/70% children in Spain); 96 eligible children received a second dose. Overall, 1042 participants completed the study. After doses 1 and 2, 98.9% and 100% of participants, respectively, returned their completed ADR card. After doses 1 and 2, 37.8% (398/1054) and 13.5% (13/96) of participants, respectively, reported at least one AE. The most frequently reported categories of AEs were "general disorders and administration site conditions" (e.g. injection site pain) and "nervous system disorders" (e.g. headache). There were no deaths or serious AEs deemed related to GSK's IIV4. CONCLUSION: This ESS study assessed AEs in near real time. The COVID-19 pandemic did not alter the safety profile of GSK's IIV4. No safety signals were detected during the study, which confirms the excellent safety profile of GSK's IIV4.

Pretherapeutic extraperitoneal laparoscopic staging of bulky or locally advanced cervical cancer.

BACKGROUND: To assess the safety, feasibility, and impact on survival of extraperitoneal para-aortic lymphadenectomy in the staging of patients with bulky or locally advanced cervical cancer. MATERIALS AND METHODS: Between August 2001 and October 2009, 87 consecutive patients (median age 5 years) with bulky or locally advanced cervical cancer underwent extraperitoneal laparoscopic infrarenal aortic and common iliac dissection as a pretherapeutic staging procedure. Data on pathologic findings, details of surgery, postoperative complications, and disease status at follow-up were collected. RESULTS: The median operating time was 150 min (range 60-255 min). The mean (± standard deviation) para-aortic nodal yield was 15.5 ± 8.1 (range 4-62). In none of the patients, conversion to the transperitoneal approach or laparotomy was necessary. Histological examination revealed metastasis in 13 patients (macroscopic disease 10, microscopic disease 3). After a median follow-up of 33.4 months (range 13.3-65.9 months), 73.6% of patients were free of disease and 1.1% were alive with disease, 19.5% died from cervical cancer, and 3.3% died from other causes. After a follow-up of 3 years, no deaths or recurrences were documented, with an overall survival rate of 74.8% (95% CI 62.8%-83.4%) and disease-free survival of 86% (95% CI 74.7%-92.5%). There were no significant differences in overall survival and disease-free survival between patients with positive and negative para-aortic lymph nodes. CONCLUSION: The extraperitoneal laparoscopic para-aortic lymphadenectomy for pretherapeutic surgical staging in cervical cancer is a safe and feasible procedure that should be considered as a tool to identify lymph node positive patients who require extended-field radiation and/or chemotherapy.

Venous thromboembolism in patients with dermatomyositis and polymyositis.

OBJECTIVES: To assess the incidence of venous thromboembolic events in dermatomyositis and polymyositis patients, and associated factors. METHODS: We retrospectively studied a cohort of 123 myositis patients (87 dermatomyositis, 36 polymyositis) from a single centre and identified cases with deep vein thrombosis and/or pulmonary embolism. Type of myositis, association with cancer, presence of thrombophilia, disease activity, and intravenous immunoglobulin therapy were analysed. Incidence rates were calculated on the basis of time to first venous thrombotic event. Patients with less than 12 months' follow-up were excluded. RESULTS: Six new first thromboembolic events occurred in 6 of 96 patients studied (6.3%), all with dermatomyositis. Median time to development of venous thromboembolism was 4.3 months (IQR, 0.8-8.8) after the dermatomyositis diagnosis. Venous thromboembolism was significantly associated with intravenous immunoglobulin therapy (p<0.05) and older age (p<0.05), but not with cancer. All events (100%) occurred during active myositis. The incidence density of venous thromboembolism among patients with dermatomyositis according to the first year of follow-up was 9.3 per 1000 person-years (95% CI, 3.4 to 20.3). CONCLUSIONS: A trend toward venous thromboembolism was detected in patients with dermatomyositis.

Safety Profile of GSK's Inactivated Quadrivalent Seasonal Influenza Vaccine in Belgium, Germany and Spain: Passive Enhanced Safety Surveillance Study for the 2019/2020 Influenza Season.

INTRODUCTION: Seasonal influenza infects millions annually in Europe. Annual influenza vaccination is the most effective measure to reduce the risk of infection and its complications, especially among young children and older adults. OBJECTIVE: We assessed adverse event (AE) frequency after receiving GSK's inactivated quadrivalent seasonal influenza vaccine (IIV4). METHODS: A passive enhanced safety surveillance study was conducted in Belgium, Germany, and Spain. Adults who had received GSK's IIV4 or the parent(s)/guardian(s)/legally acceptable representative(s) of children given the vaccine were invited to complete an adverse drug reaction (ADR) card to document AEs experienced within 7 days post vaccination. RESULTS: A total of 1082 participants (51.6% females) received GSK's IIV4, including 115 children < 9 years of age who received two doses. The ADR card return rate was 97.0% (n = 1049) after dose 1 and 100% (n = 115) after dose 2. All participants in Belgium and Germany were adults. In Spain, 71.2% were children. After dose 1, 39.2% reported one or more AE. The most frequent AEs category was "general disorders and administration site conditions" (GDASC). AEs were most frequently reported in adults aged 18-65 years (47.2%), followed by children aged 6 months-17 years (38.1%), and adults aged > 65 years (31.6%). After dose 2, 7.8% reported one or more AE, and GDASC was again the most frequent AE category. There were no serious AEs related to GSK's IIV4 within 7 days post vaccination. CONCLUSION: No serious AEs related to GSK's IIV4 within 7 days post vaccination were reported. This study supports the favourable risk-benefit safety profile of GSK's IIV4.

Seasonal influenza infects millions annually in Europe, especially young children and older adults. Annual influenza vaccination is the most effective measure to reduce the risk of infection and its complications. As the wild influenza virus strains change every year, the composition of the influenza vaccine changes as well. Since the vaccine is produced in the same way over the years, extensive safety studies are no longer required by regulatory authorities. Instead, monitoring of any unwanted medical incidents (adverse events) after vaccination is required. For the 2019/2020 season, we monitored the adverse events reported by a representative sample of people in Belgium, Germany, and Spain within 7 days after receiving GSK's seasonal influenza vaccine.Of the 1082 people who received the first dose of the vaccine, 39% reported at least one adverse event, such as pain and swelling at the injection site, tiredness, fever, headache, or dizziness. A total of 115 children under 9 years of age received two doses 4 weeks apart. After their second dose, few of these children (8%) reported adverse events. The most frequent adverse events were fever, swelling and pain at the injection site, runny nose, or irritability. No serious adverse events were reported after either the first or second dose.No serious adverse events related to GSK's seasonal influenza vaccine within the 7 days after vaccination were reported. This study supports the favourable risk­benefit safety profile of GSK's seasonal influenza vaccine.