Higher mortality risk from gynaecological neoplasms and non-Hodgkin's lymphoma in patients with systemic lupus erythematosus: an observational study from the Spanish National Registry.

OBJECTIVE: To evaluate the impact of the different types of neoplasms and lineages on mortality of patients with SLE. METHODS: Retrospective and observational comparison of the neoplasm-related deaths in patients with SLE and the general Spanish population reported in the Spanish Hospital Discharge Database. To determine the impact of SLE on the risk of dying from each neoplasm lineage, a binary logistic regression considering age, female sex, tobacco and alcohol consumption, was performed. RESULTS: During 2016-2019, 139 531 in-hospital deaths from neoplasms were certified in Spain (91 in patients with SLE). Patients with SLE presented a lower mortality rate from solid organ neoplasms, (80.2% vs 91.1%, OR 0.393), linked to their lower risk of colorectal carcinoma (1.1% vs 10.8%, OR 0.110). By contrast, gynaecological neoplasms presented a higher risk (8.8% vs 3%, OR 3.039) in the deceased patients with SLE, associated with the higher frequency of vulvar neoplasms (2% vs 0.2%, OR 14.767) and cervical carcinomas (3.3% vs 0.5%, OR 3.809). Haematological neoplasm-related deaths were also more prevalent in patients with SLE (19.8% vs 8.9%, OR 2.546), mostly attributable to the higher proportion of deaths due to non-Hodgkin's lymphoma (11% vs 2.9%, OR 4.060) of B cell lineage (9.9% vs 2.5%, OR 4.133). CONCLUSIONS: Patients with SLE present a higher risk of death from vulvar neoplasms, cervical carcinomas and B-cell non-Hodgkin's lymphoma in comparison with the general Spanish population. In addition to developing strategies that might help to attenuate their occurrence and impact, such as decreasing the immunosuppressive burden, specific early detection programmes for these conditions should be investigated and considered carefully.

Prospects for Controlling Hepatitis B Globally.

Infection with the hepatitis B virus (HBV) is highly prevalent globally. Over 250 million people suffer from chronic hepatitis B, and more than 800,000 patients die each year due to hepatitis B complications, including liver cancer. Although protective HBV vaccines are recommended for all newborns, global coverage is suboptimal. In adults, sexual transmission is by far the most frequent route of contagion. The WHO estimates that 1.5 million new HBV infections occur annually. Oral nucleos(t)ide analogues entecavir and tenofovir are the most frequent antivirals prescribed as HBV therapy. Almost all patients adherent to the medication achieve undetectable plasma viremia beyond 6 months of monotherapy. However, less than 5% achieve anti-HBs seroconversion, and viral rebound occurs following drug discontinuation. Therefore, nucleos(t)ide analogues need to be lifelong. New long-acting formulations of tenofovir and entecavir are being developed that will maximize treatment benefit and overcome adherence barriers. Furthermore, new antiviral agents are in development, including entry inhibitors, capside assembly modulators, and RNA interference molecules. The use of combination therapy pursues a functional HBV cure, meaning it is negative for both circulating HBV-DNA and HBsAg. Even when this goal is achieved, the cccDNA reservoir within infected hepatocytes remains a signal of past infection, and HBV can reactivate under immune suppression. Therefore, new gene therapies, including gene editing, are eagerly being pursued to silence or definitively disrupt HBV genomes within infected hepatocytes and, in this way, ultimately cure hepatitis B. At this time, three actions can be taken to push HBV eradication globally: (1) expand universal newborn HBV vaccination; (2) perform once-in-life testing of all adults to identify susceptible HBV persons that could be vaccinated (or re-vaccinated) and unveil asymptomatic carriers that could benefit from treatment; and (3) provide earlier antiviral therapy to chronic HBV carriers, as being aviremic reduces the risk of both clinical progression and transmission.

Sarcoidosis and lymphoma mortality risk: An observational study from the Spanish National Registry.

Introduction: Patients with sarcoidosis have a lower survival rate than the general population, in part due to cardiovascular disease, infections and neoplasms. Our objective was to evaluate the impact of haematological neoplasms (HN) and lymphomas on sarcoidosis patient mortality in a nation-wide analysis conducted in Spain, a country with a population of 47 million. Methods: Retrospective and observational comparison of the HN related deaths in sarcoidosis patients and the general Spanish population reported in the Spanish Hospital Discharge Database. To determine the impact of sarcoidosis on the risk of dying from each HN lineage, a binary logistic regression considering age, female sex, tobacco and alcohol consumption, was performed. Results: In the period 2016 and 2019, 139,531 in-hospital deaths from neoplasms were certified in Spain (77 in patients with sarcoidosis). Patients with sarcoidosis died at younger age than the general Spanish population (72.9 vs 77.6, p<0.001). Sarcoidosis patients presented a higher mortality risk from HN (20.8% vs 8.9%, p=0.001, OR=2.64, 95% CI 1.52-4.59), attributable to the higher proportion of deaths from non-Hodgkin lymphoma (NHL), (9.2% vs 2.9%, p=0.006, OR= 3.33, 95% CI 1.53-7.25) from both B cell (6.6% vs 2.5%, p=0.044, OR= 2.62, 95% 1.06-6.5) and T/NK cell lineages (2.6% vs 0.3%, p=0.024, OR= 7.88, 95% CI 1.92-32.29) as well as HN with uncertain behavior and myeloproliferative disorders (2.6% vs 0.3%, p=0.018, OR= 11.88, 95% CI 2.88-49.02). The mean age of sarcoidosis patients who died from HN (63.6 vs 71.9, p=0.032) and non-Hodgkin lymphoma (56.9 vs 71, p=0.009) was lower than that of the general population. Conclusion: Patients with sarcoidosis present a higher risk of premature death from HN, including NHL from B, T/NK cell lineage and myeloproliferative disorders in comparison with the general Spanish population. In addition to developing strategies that might help to attenuate their occurrence and impact, such as decreasing the immunosuppressive burden, specific early-detection programs for these conditions should be investigated and considered carefully.

Trends in epidemiology, surgical management, and prognosis of infective endocarditis during the XXI century in Spain: A population-based nationwide study.

BACKGROUND: Few population-based studies have evaluated the epidemiology of infective endocarditis (IE). Changes in population demographics and guidelines on IE may have affected both the incidence and outcomes of IE. Therefore, the aim of our study is to provide contemporary population-based epidemiological data of IE in Spain. METHODS: Retrospective nationwide observational study using data from the Spanish National Health System Discharge Database. We included all patients hospitalized with IE from January 2000 to December 2019. RESULTS: A total of 64,550 IE episodes were included. The incidence of IE rose from 5.25 cases/100,000 person-year in 2000 to 7.21 in 2019, with a 2% annual percentage change (95% CI 1.3-2.6). IE incidence was higher among those aged 85 or older (43.5 cases/100.000 person-years). Trends across the study period varied with sex and age. Patients with IE were progressively older (63.9 years in 2000-2004 to 70.0 in 2015-2019, p < 0.001) and had more frequent comorbidities and predispositions, including, previous valvular prosthesis (12.1% vs 20.9%, p < 0.001). After adjustment, a progressive reduction in mortality was noted including in 2015-2019 compared to 2010-2014 (adjusted odds ratio 0.93, 95% confident interval 0.88-0.99, p = 0.023)., which was associated with more frequent cardiac surgery in recent years (15.1% in 2010-2014 vs 19.9% in 2015-2019). CONCLUSIONS: In Spain, the incidence of IE has increased during the XXI century, with a more pronounced increase in elderly individuals. Adjusted-mortality decreased over the years, which could be related to a higher percentage of surgery. Our results highlight the changing epidemiology of IE.

Methyl-Prednisolone Pulses and Prolonged Remission in Systemic Lupus Erythematosus: A Propensity Score Analysis of the Longitudinal Lupus-Cruces-Bordeaux Inception Cohort.

OBJECTIVES: To analyze the effect of methyl-prednisolone pulses (MP), given during the first year after the diagnosis of systemic lupus erythematosus (SLE), in achieving prolonged remission according to the degree of lupus activity at presentation. METHODS: Observational study of routine clinical care data of the Lupus Cruces-Bordeaux cohort. The endpoint was prolonged remission, i.e. during 5 consecutive yearly visits. The effect on remission of MP during the first year was analyzed in the whole cohort and according to the baseline SLEDAI-2K score: <6, 6-12 and >12, reflecting mild, moderate and severe activity, respectively. For adjustment, logistic regression with propensity score (PE) and other therapeutic covariates was performed. RESULTS: Two hundred thirty-three patients were included. Prolonged remission was achieved by 132 (57%) patients. MP were associated with prolonged remission (PE-adjusted OR 2.50, 95%CI 1.04-623, p=0.042). A strong clinical effect was seen among patients with moderate (adjusted OR 5.28, 95%CI 1.27-21.97, p=0.022) and with moderate-severe SLE activity (adjusted OR 4.07, 95%CI 1.11-14.82, p=0.033). The administration of MP resulted in reduced average doses of prednisone during the first year among patient with moderate (mean 6.6 vs 10.2 mg/d, p=0.017) and severe activity (mean 14 vs. 28 mg/d, p= 0.015). The odd of prolonged remission was increased by longer-term use of HCQ and decreased by higher initial doses of prednisone. CONCLUSIONS: This study supports the use of MP to induce prolonged remission in patients with SLE, particularly in those with moderate and severe activity. The extended use of HCQ also contributes to achieve prolonged remission. This article is protected by copyright. All rights reserved.

Pre-exposure prophylaxis of non-HIV viral infections and the role of long-acting antivirals.

Viruses cause a large burden of human infectious diseases. During the past 50 years, antivirals have been developed to treat many pathogenic viruses, including herpesviruses, retroviruses, hepatitis viruses, and influenza. Besides being used as treatment, antivirals have shown efficacy for preventing certain viral infections. Following the success in the HIV field, a renewed interest has emerged on the use of antivirals as prophylaxis for other viruses. The development of formulations with extended half-life has pushed further this consideration in persons at risk for a wide range of viral infections. In this way, long-acting antivirals might behave as "chemovaccines" when classical vaccines do not exist, cannot be recommended, immune responses are suboptimal, escape mutants emerge, and/or immunity wanes. Five main caveats would temper its use, namely, selection of drug resistance, drug interactions, short- and long-term side effects, potential teratogenicity in women of child-bearing age, and high cost. Herein, we discuss the prospects for long-acting antivirals as prophylaxis of human viral infections other than HIV.

Genetic signature detected in T cell receptors from patients with severe COVID-19.

Characterization of host genetic factors contributing to COVID-19 severity promises advances on drug discovery to fight the disease. Most genetic analyses to date have identified genome-wide significant associations involving loss-of-function variants for immune response pathways. Despite accumulating evidence supporting a role for T cells in COVID-19 severity, no definitive genetic markers have been found to support an involvement of T cell responses. We analyzed 205 whole exomes from both a well-characterized cohort of hospitalized severe COVID-19 patients and controls. Significantly enriched high impact alleles were found for 25 variants within the T cell receptor beta (TRB) locus on chromosome 7. Although most of these alleles were found in heterozygosis, at least three or more in TRBV6-5, TRBV7-3, TRBV7-6, TRBV7-7, and TRBV10-1 suggested a possible TRB loss of function via compound heterozygosis. This loss-of-function in TRB genes supports suboptimal or dysfunctional T cell responses as a major contributor to severe COVID-19 pathogenesis.

Impact of the COVID-19 pandemic on hospital admissions due to viral hepatitis in Spain.

BACKGROUND: Before the advent of COVID-19 vaccines, hospitalizations due to SARS-CoV-2 infection during 2020 collapsed most medical centers worldwide. Disruptions in health care for clinical conditions other than COVID-19 were not uniform. Herein, we report the impact of COVID-19 on hospitalizations due to viral hepatitis in Spain. METHODS: Retrospective study of all hospitalizations in Spain during 10 months before (pre-pandemic period) and after (pandemic period) March 1st 2020. Admissions with a diagnosis of hepatitis B, C and/or delta were retrieved and compared using the Spanish National Registry of Hospital Discharges. RESULTS: Nationwide hospitalizations declined 14.6% during the pandemic period, from 3,144,164 to 2,684,845. This reduction was significantly more pronounced for admissions due to viral hepatitis (18.1% drop), falling from 46,521 to 38,115. During the pandemic period, patients admitted with viral hepatitis died significantly more frequently than during the pre-pandemic period (7.2% vs 6.1%; p < 0.001). Liver transplants significantly declined during the pandemic period. COVID-19 was diagnosed in 10.3% of patients hospitalized with viral hepatitis during the pandemic period. This subset of patients was older and died 2.4-fold more frequently than the rest, despite having advanced liver disease less frequently. CONCLUSION: Hospitalizations due to viral hepatitis significantly declined in Spain during the COVID-19 pandemic. Patients admitted with viral hepatitis experienced a greater mortality during the pandemic period. Deaths were more pronounced when coinfected with SARS-CoV-2 despite having advanced liver disease less frequently.

Prevalence and impact of cerebrovascular risk factors in patients with giant cell arteritis: An observational study from the Spanish national registry / Prevalencia e impacto de los factores de riesgo cerebrovascular en pacientes con arteritis de células gigantes: un estudio observacional del registro nacional español

Objective To assess the prevalence and impact of cerebrovascular risk factors (CRF) on cerebrovascular events (CVE) in patients with giant cell arteritis (GCA). Methods Analysis of the patients diagnosed with GCA identified in the Spanish Hospital Discharge Database between 2016 and 2018. Results 8,474 hospital admissions from patients diagnosed with GCA were identified. 3.4% of the admissions were motivated by CVE (stroke in 2.8% and transient ischemic attack in 0.6%). When compared with the admissions due to other causes, the patients who suffered from CVE presented a higher rate of male sex (36.2% vs 43.5%, p=0.007), hypertension (66.9% vs 74.4%, p=0.004), diabetes (27.6% vs 33.7%, p=0.016) and atherosclerosis (6.6% vs 10.2%, p=0.0.017). After adjustment, male sex (OR=1.35, 95% CI 1.06–1.72) and mainly hypertension (OR=1.44, 95% CI 1.11–1.90) were associated with a higher risk of CVE. Conclusion Hypertension, along with male sex, was the strongest risk factor for cerebrovascular events in GCA patients. In these high-risk patients, antiplatelet therapy should be re-considered and evaluated in prospective studies (AU)

Objetivo Evaluar la prevalencia e impacto de los factores de riesgo cerebrovasculares en los episodios cerebrovasculares (ECV) de pacientes con arteritis de células gigantes (ACG). Métodos Análisis de los pacientes diagnosticados con ACG identificados en la base de altas hospitalarias española entre 2016 y 2018. Resultados Se identificaron 8.474 ingresos hospitalarios en pacientes diagnosticados de ACG. El 3,4% de los ingresos se atribuyó a ECV (ictus en 2,8% y accidente isquémico transitorio en 0,6%). En comparación con los ingresos por otras causas, los pacientes que presentaron ECV mostraron una mayor tasa de sexo masculino (36,2 frente a 43,5%, p=0,007), hipertensión (66,9 frente a 74,4%, p=0,004), diabetes (27,6 frente a 33,7%, p=0,016) y aterosclerosis (6,6 frente a 10,2%, p=0,0017). Tras el ajuste, el sexo masculino (OR=1,35, IC 95% 1,06-1,72) y principalmente la hipertensión (OR=1,44, IC 95% 1,11-1,90) se asociaron con un mayor riesgo de ECV. Conclusión La hipertensión, junto con el sexo masculino, fueron los principales factores de riesgo de ECV en los pacientes con ACG. En estos pacientes de alto riesgo, el tratamiento con antiagregantes debería reconsiderarse y evaluarse en estudios prospectivos (AU)

COVID-19 in hospitalized solid organ transplant recipients in a nationwide registry study.

OBJECTIVES: Underlying immunodeficiency has been associated with worse clinical presentation and increased mortality in patients with COVID-19. We evaluated the mortality of solid organ transplant (SOT) recipients (SOTR) hospitalized in Spain due to COVID-19. METHODS: Nationwide, retrospective, observational analysis of all adults hospitalized because of COVID-19 in Spain during 2020. Stratification was made according to SOT status. The National Registry of Hospital Discharges was used, using the International Classification of Diseases, 10th revision coding list. RESULTS: Of the 117,694 adults hospitalized during this period, 491 were SOTR: kidney 390 (79.4%), liver 59 (12%), lung 27 (5.5%), and heart 19 (3.9%). Overall, the mortality of SOTR was 13.8%. After adjustment for baseline characteristics, SOTR was not associated with higher mortality risk (odds ratio [OR] = 0.79, 95% confidence interval [CI] 0.60-1.03). However, lung transplantation was an independent factor related to mortality (OR = 3.26, 95% CI 1.33-7.43), while kidney, liver, and heart transplantation were not. Being a lung transplant recipient was the strongest prognostic factor in SOT patients (OR = 5.12, 95% CI 1.88-13.98). CONCLUSION: This nationwide study supports that the COVID-19 mortality rate in SOTR in Spain during 2020 did not differ from the general population, except for lung transplant recipients, who presented worse outcomes. Efforts should be focused on the optimal management of lung transplant recipients with COVID-19.

Effect of the implementation of clinical guidelines on management of candidemia in elderly patients.

INTRODUCTION: Mortality from candidemia is higher in elderly population than in younger patients, which may be related to suboptimal management. The aim of the present study is to evaluate adherence to the recommendations for the clinical management of candidemia in a population over 75 years before and after implementing specific training. PATIENTS AND METHODS: We recorded retrospectively data from candidemia episodes in elderly patients during two periods of time: 2010-2015 years (before training) and 2017-2022 years (after training), as well as adherence to the recommendations of the clinical practice guidelines, mortality and consultation to infectious disease specialists. RESULTS: Forty-five episodes of candidemia were recorded in the first period and 29 episodes in the second period. A better compliance to the recommendations of the clinical practice guidelines was observed in the second period: echocardiogram performance (75.9% vs. 48.9% p = .021), fundoscopy (65.5% vs. 44.4% p = .076), follow-up blood cultures (72.4% vs. 42.2% p = .011), removal of central venous catheter (80% vs. 52.9% p = .080) and adequate antifungal treatment (82.6% vs. 52.6% p = .018). A trend towards lower mortality was observed during the second period (27.6% vs. 44.4% p = .144). CONCLUSION: The improvement of knowledge of clinical guidelines on candidemia and the participation of infectious disease specialists may increase the quality of care in elderly patients with candidemia. It would be necessary to enlarge the sample size to evaluate the real impact of this intervention on mortality.

Safety considerations in the management of hepatitis C and HIV co-infection.

INTRODUCTION: Both HCV and HIV are highly prevalent infections with current estimates of 57 and 38 million people infected worldwide, respectively. Oral antivirals can be curative for HCV and rescue HIV patients from disease progression. Dual therapy in coinfected patients requires expertise. AREAS COVERED: Four major issues challenge dual HCV and HIV treatment, including overlapping drug-related side effects, hepatitis B reactivation, immune reconstitution inflammatory syndromes (IRIS), and drug-drug interactions (DDI). A search was conducted in PubMed from January 2010 to March 2023. EXPERT OPINION: The advent of second-generation direct-acting antivirals (DDA) that depict higher antiviral potency, fewer side effects, pangenotypic activity and are co-formulated has expanded the indication of HCV therapy and particularly in HIV-coinfected individuals. Sequential initiation of antiretrovirals (ARV) followed by DAA is generally preferred to start dual treatment concomitantly. Close monitoring of rare episodes of HBV reactivation and IRIS is warranted. The most frequent DDI between DAA and ARV affect drug metabolism by CYP450 induction/inhibition, leading to abnormal drug exposures. Throughout this mechanism interact most HCV and HIV protease inhibitors and non-nucleoside polymerase inhibitors. Exposure to some HIV and HCV nucleos(t)ide analogues (e.g. tenofovir and sofosbuvir, respectively) is subject to induction/inhibition of drug transporters and requires special attention in patients with renal insufficiency.

Prevalence and impact of cerebrovascular risk factors in patients with giant cell arteritis: An observational study from the Spanish national registry.

OBJECTIVE: To assess the prevalence and impact of cerebrovascular risk factors (CRF) on cerebrovascular events (CVE) in patients with giant cell arteritis (GCA). METHODS: Analysis of the patients diagnosed with GCA identified in the Spanish Hospital Discharge Database between 2016 and 2018. RESULTS: 8,474 hospital admissions from patients diagnosed with GCA were identified. 3.4% of the admissions were motivated by CVE (stroke in 2.8% and transient ischemic attack in 0.6%). When compared with the admissions due to other causes, the patients who suffered from CVE presented a higher rate of male sex (36.2% vs 43.5%, p=0.007), hypertension (66.9% vs 74.4%, p=0.004), diabetes (27.6% vs 33.7%, p=0.016) and atherosclerosis (6.6% vs 10.2%, p=0.0.017). After adjustment, male sex (OR=1.35, 95% CI 1.06-1.72) and mainly hypertension (OR=1.44, 95% CI 1.11-1.90) were associated with a higher risk of CVE. CONCLUSION: Hypertension, along with male sex, was the strongest risk factor for cerebrovascular events in GCA patients. In these high-risk patients, antiplatelet therapy should be re-considered and evaluated in prospective studies.

Increased incidence of giant cell arteritis and associated stroke during the COVID-19 pandemic in Spain: A nation-wide population study.

INTRODUCTION: SARS-CoV-2 infection and COVID-19 vaccines might have increased the incidence of giant-cell arteritis (GCA) and the risk of associated stroke in Spain. METHODS: Retrospective nation-wide observational analysis of all adults hospitalized with GCA in Spain during 5 years (Jan-2016 and Dec-2021). The incidence and proportion of admissions with or because of GCA and GCA-associated stroke were compared between pre-pandemic (2016-2019) and pandemic (2020 and 2021) years. Sensitivity analyses were conducted for the different COVID-19 waves and vaccine timing schedules. RESULTS: A total of 17,268 hospital admissions in patients diagnosed with GCA were identified. During 2020 there were 79.3 and 8.1 per 100,000 admissions of GCA and GCA-associated stroke, respectively. During 2021 these figures were 80.8 and 7.7 per 100,00 admissions, respectively. As comparison, yearly admissions due to GCA and GCA-associated stroke were 72.4 and 5.7 per 100,00, respectively, during the pre-pandemic period (p < 0.05). Coincident with the third wave of COVID-19 (and first vaccine dosing), the rate of GCA-associated stroke admissions increased significantly (from 6.7 to 12%; p < 0.001). Likewise, there was an increase in GCA-associated stroke (6.6% vs 4.1%, p = 0.016) coincident with the third dose vaccination (booster) in patients older than 70 at the end of 2021. In multivariate analysis, only patients admitted during the third COVID-19 wave (and first vaccine dosing) (OR = 1.89, 95% CI 1.22-2.93), and during the third vaccination dosing in patients older than 70 (booster) (OR = 1.66, CI 1.11-2.49), presented a higher GCA-associated stroke risk than the same months of previous years after adjustment by age, sex, classical cardiovascular risk factors and COVID-19 diagnosis. CONCLUSIONS: The COVID-19 pandemic led to an increased incidence of GCA during 2020 and 2021. Moreover, the risk of associated stroke significantly risen accompanying times of COVID-19 vaccine dosing, hypothetically linked to an increased thrombotic risk of mRNA-SARS-CoV-2 vaccines. Hence, forthcoming vaccine policies and indications must weigh the risk of severe COVID-19 with the risk of flare or stroke in patients with GCA.