Trace Element Imbalances in Acquired Hepatocerebral Degeneration and Changes after Liver Transplant.

Brain manganese (Mn) accumulation is a key feature in patients with acquired hepatocerebral degeneration (AHD). The role of trace elements other than Mn in AHD needs to be clarified. In this study, using inductively coupled plasma mass spectrometry, we aimed to evaluate blood levels of trace elements in patients with AHD before and after liver transplantation (LT). Trace element levels in the AHD group were also compared with those of healthy controls (blood donors, n = 51). Fifty-one AHD patients were included in the study (mean age: 59.2 ± 10.6 years; men: 72.5%). AHD patients had higher levels of Mn, Li, B, Ni, As, Sr, Mo, Cd, Sb, Tl and Pb and a higher Cu/Se ratio, and lower levels of Se and Rb. Six patients (two women; mean age 55 ± 8.7 years) underwent LT, and there was an improvement in neurological symptoms, a significant increase in the Zn, Se and Sr levels, and a decrease in the Cu/Zn and Cu/Se ratios. In summary, several trace element imbalances were identified in AHD patients. Liver transplantation resulted in the improvement of neurological manifestations and the oxidant/inflammatory status. It is possible that observed changes in trace element levels may play a role in the pathophysiology and symptomatology of AHD.

Variation of Hg concentration and accumulation in the soil of maritime pine plantations along a coast-inland transect in SW Europe.

Climatic conditions have been shown as a major driver of the fate of Hg in forest ecosystems at a global scale, but less is known about climatic effects at shorter scales. This study assesses whether the concentration and pools of Hg in soils collected from seventeen Pinus pinaster stands describing a coastal-inland transect in SW Europe vary along a regional climatic gradient. In each stand, samples of the organic subhorizons (OL, OF + OH) and the mineral soil (up to 40 cm) were collected and some general physico-chemical properties and total Hg (THg) were analyzed. Total Hg was significantly higher in the OF + OH than in the OL subhorizons (98 and 38 µg kg-1, respectively), favored by a greater organic matter humification in the former. In the mineral soil, mean THg values decreased with depth, ranging from 96 µg kg-1 in the 0-5 cm layers to 54 µg kg-1 in the deepest layers (30-40 cm), respectively. The average Hg pool (PHg) was 0.30 mg m-2 in the organic horizons (92% accumulated in the OF + OH subhorizons), and 27.4 mg m-2 in the mineral soil. Changes in climatic factors, mainly precipitation, along the coast-inland transect resulted in a remarkable variation of THg in the OL subhorizons, consistent with their role as the first receiver of atmospheric Hg inputs. The high precipitation rate and the occurrence of fogs in coastal areas characterized by the oceanic influence would explain the higher THg found in the uppermost soil layers of pine stands located close to the coastline. The regional climate is key to the fate of mercury in forest ecosystems by influencing the plant growth and subsequent atmospheric Hg uptake, the atmospheric Hg transference to the soil surface (wet and dry deposition and litterfall) and the dynamics that determine net Hg accumulation in the forest floor.

Mercury in a birch forest in SW Europe: Deposition flux by litterfall and pools in aboveground tree biomass and soils.

Atmospheric mercury (Hg) is largely assimilated by vegetation and subsequently transferred to the soil by litterfall, which highlights the role of forests as one of the largest global Hg sinks within terrestrial ecosystems. We assessed the pool of Hg in the aboveground biomass (leaves, wood, bark, branches and twigs), the Hg deposition flux through litterfall over two years (by sorting fallen biomass in leaves, twigs, reproductive structures and miscellaneous) and its accumulation in the soil profile in a deciduous forest dominated by Betula alba from SW Europe. The total Hg pool in the aboveground birch biomass was in the range 532-683 mg ha-1, showing the following distribution by plant tissues: well-developed leaves (171 mg ha-1) > twigs (160 mg ha-1) > bark (159 mg ha-1) > bole wood (145 mg ha-1) > fine branches (25 mg ha-1) > thick branches (24 mg ha-1) > newly sprouted leaves (20 mg ha-1). The total Hg deposition fluxes through litterfall were 15.4 and 11.7 µg m-2 yr-1 for the two years studied, with the greatest contribution coming from birch leaves (73 %). In the soil profile, the pool of Hg in the mineral soil (37.0 mg m-2) was an order of magnitude higher than in the organic horizons (1.0 mg m-2), mostly conditioned by parameters such as soil bulk density and thickness, total C and N contents and the presence of certain Al compounds.

Needle age and precipitation as drivers of Hg accumulation and deposition in coniferous forests from a southwestern European Atlantic region.

Vegetation and climate are critical in the biogeochemical cycle of Hg in forest ecosystems. The study assesses the influence of needle age and precipitation on the accumulation of Hg in needle biomass and its deposition by litterfall in thirty-one pine plantations spread throughout two biogeographical regions in SW Europe. Well-developed branches of Pinus pinaster were sampled and pine needles were classified according to 4 age classes (y0, y1, y2, y3). The concentration of total Hg (THg) was analyzed in the samples and Hg content in needle biomass and its deposition by litterfall were estimated. The concentration of total Hg (THg) increased with needle age ranging from 9.1 to 32.7 µg Hg kg-1 in the youngest and oldest needles, respectively. The rate of Hg uptake (HgR) three years after needle sprouting was 10.2 ± 2.3 µg Hg kg-1 yr-1, but it decreased with needle age probably due to a diminution in photosynthetic activity as needles get older. The average total Hg stored in needle biomass (HgWt) ranged from 5.6 to 87.8 mg Hg ha-1, with intermediate needle age classes (y1 and y2) accounting for 70% of the total Hg stored in the whole needle biomass. The average deposition flux of Hg through needle litterfall (HgLt) was 1.5 µg Hg m-2 yr-1, with the y2 and y3 needles contributing most to the total Hg flux. The spatial variation of THg, HgWt and HgLt decreased from coastal pine stands, characterized by an oceanic climate, to inland pine stands, a feature closely related to the dominant precipitation regime in the study area. Climatic conditions and needle age are the main factors affecting Hg accumulation in tree foliage, and should be considered for an accurate assessment of forest Hg pools at a regional scale and their potential consequences in the functioning of terrestrial ecosystems.

Susceptibility and risk of SARS-COV-2 infection among middle-aged and older adults in Tarragona area, Spain.

Objective: To analyse susceptibility/risk of suffering COVID-19 among adults with distinct underlying medical conditions. Methods: Population-based cohort study involving 79,083 individuals ≥50 years old in Tarragona (Southern Catalonia, Spain). Baseline cohort characteristics (demographic, pre-existing comorbidities, chronic medications and vaccinations history) were established at study start (01/03/2020) and primary outcome was laboratory-confirmed COVID-19 occurred among cohort members throughout 01/03/2020-30/06/2020. Risk of suffering COVID-19 was evaluated by Cox regression, estimating multivariable hazard ratios (HRs) adjusted for age/sex and pre-existing comorbidities. Results: Across study period, 536 laboratory-confirmed COVID-19 cases were observed (mean incidence: 39.5 cases per 100,000 persons-week). In multivariable-analysis, increasing age/years (HR: 1.01; 95% CI: 1.00-1.02), nursing-home (HR: 20.19; 95% CI: 15.98-25.51), neurological disease (HR: 1.35; 95% CI: 1.03-1.77), taking diuretics (HR: 1.39; 95% CI: 1.10-1.75), antiplatelet (HR: 1.36; 95% CI: 1.05-1.76) and benzodiazepines (HR: 1.24; 95% CI: 1.00-1.53) increased risk; conversely, taking angiotensin-converting-enzyme inhibitors (HR: 0.78; 95% CI: 0.61-1.00), angiotensin-receptor-blockers (HR: 0.70; 95%CI: 0.51-0.96) and statins (HR: 0.75; 95% CI: 0.58-0.96) were associated with reduced risk. Among community-dwelling individuals, pre-existing cancer, renal and cardiac disease appeared also related with an increased risk, whereas influenza vaccination was associated with reduced risk. Conclusion: In a setting with relatively low incidence of COVID-19 across the first wave of pandemic period, increasing age, nursing-home residence and multiple comorbidities appear predisposing for COVID-19 among middle-aged/older adults. Conversely, statins, angiotensin-receptor blockers/inhibitors and influenza vaccination were related with decreased risk.

Objetivo: Analizar incidencia y riesgo/susceptibilidad de sufrir la COVID-19 en adultos según distintas condiciones médicas preexistentes. Métodos: Cohorte de base poblacional que incluyó 79.083 personas ≥50 años en Tarragona. Características basales de la cohorte (edad/sexo, comorbilidades, medicaciones crónicas) se establecieron a 01-03-2020 y se registraron todos los casos de COVID-19 confirmada ocurridos en miembros de la cohorte hasta el 30-06-2020. Para estimación de riesgos se realizó regresión de Cox, con cálculo de hazard ratio (HR) ajustados por edad, sexo y comorbilidad. Resultados: Se observaron 536 casos confirmados de COVID-19 (incidencia media: 39,5 casos por 100.000 personas-semana). En análisis multivariante, edad/años (HR: 1,01; IC el 95%: 1,00-1,02; p = 0,050), estar institucionalizado/residencia (HR: 20,19; IC 95%: 15,98-25,51; p<0,001), enfermedad neurológica (HR: 1,35; IC el 95%: 1,03-1,77), diuréticos (HR: 1,39; IC 95%: 1,10-1,75), antiagregantes plaquetarios (HR: 1,36; IC 95%: 1,05-1,76) y benzodiacepinas (HR: 1,24; IC 95%: 1,00-1,53) se asociaron con un riesgo aumentado de la COVID-19 analizando la totalidad de la cohorte; contrariamente, medicación IECA (HR: 0,78; IC el 95%: 0,61-1,00), ARA-II (HR: 0,70; IC el 95%: 0,51-0,96) y estatinas (HR: 0,75; IC el 95%: 0,58-0,96) se asociaron con menor riesgo. Entre personas no institucionalizadas, cáncer, nefropatía y cardiopatía se asociaron con mayor riesgo y vacunación antigripal con menor riesgo. Conclusión: En un área con relativamente baja incidencia de COVID-19, edad, institucionalización y múltiples comorbilidades aumentaron el riesgo/susceptibilidad de sufrir la COVID-19. Contrariamente, estatinas, inhibidores del sistema renina-angiotensina y vacunación antigripal se asociaron con menor riesgo.

Extramedullary Acute Leukemia-Still an Unforeseen Presentation.

Myeloid sarcomas (MS) are rare extramedullary (EM) hematological tumors that generally arise during the natural course of acute myeloid leukemia (AML), occurring concomitantly with the onset of systemic leukemia; it can also occur following onset but rarely before. Common sites of EM involvement include the lymph nodes, skin, soft tissue, bone and peritoneum. Herein, we report the case of a 63-year-old man who presented EM AML upon initial diagnosis involving the bone marrow, lymph nodes and skin (leukemia cutis). A diagnosis was made based on immunohistochemistry (IHC). This case presents a diagnostic dilemma due to its atypical presentation and the sites involved. It also highlights the importance of IHC in the diagnosis of EM AML. The potential role of hypomethylating agents and Venetoclax in cases not eligible for hematopoietic stem cell transplant are also discussed.

Efficacy of Telemedicine and At-Home Telemonitoring following Hospital Discharge in Patients with COVID-19.

Aim: This work aims to evaluate the safety and utility of an at-home telemedicine with telemonitoring program for discharged COVID-19 patients. Methods: This is a retrospective cohort study of all patients discharged home in Galicia between 6 March 2020 and 15 February 2021. We evaluated a structured, proactive monitoring program conducted by the ASLAM (Área Sanitaria de Lugo, A Mariña y Monforte de Lemos) Healthcare Area team compared to patients discharged in the rest of the Autonomous Community of Galicia. Results: During the study period, 10,517 patients were hospitalized for COVID-19 and 8601 (81.8%) were discharged. Of them, 738 (8.6%) were discharged in ASLAM and 7863 (91.4%) were discharged in the rest of Galicia. Of those discharged in ASLAM, 475 (64.4%) patients were monitored. Compared to patients in the rest of Galicia, the group monitored via telemedicine had a significantly shorter first hospital stay (p < 0.0001), a lower readmission rate (p = 0.05), and a shorter second hospital stay (p = 0.04), with no differences in emergency department visits or 90-day all-cause mortality. Conclusion: A structured, proactive telemedicine with telemonitoring program for discharged COVID-19 patients is a safe, useful tool that reduces the mean length of hospital stay and readmissions.

Susceptibility and risk of SARS-COV-2 infection among middle-aged and older adults in Tarragona area, Spain / Susceptibilidad y riesgo de infección por SARS-CoV-2 en adultos mayores de 50 años en el área de Tarragona

Objective:To analyse susceptibility/risk of suffering COVID-19 among adults with distinct underlying medical conditions.Methods:Population-based cohort study involving 79,083 individuals ≥50 years old in Tarragona (Southern Catalonia, Spain). Baseline cohort characteristics (demographic, pre-existing comorbidities, chronic medications and vaccinations history) were established at study start (01/03/2020) and primary outcome was laboratory-confirmed COVID-19 occurred among cohort members throughout 01/03/2020–30/06/2020. Risk of suffering COVID-19 was evaluated by Cox regression, estimating multivariable hazard ratios (HRs) adjusted for age/sex and pre-existing comorbidities. Results:Across study period, 536 laboratory-confirmed COVID-19 cases were observed (mean incidence: 39.5 cases per 100,000 persons-week). In multivariable-analysis, increasing age/years (HR: 1.01; 95% CI: 1.00–1.02), nursing-home (HR: 20.19; 95% CI: 15.98–25.51), neurological disease (HR: 1.35; 95% CI: 1.03–1.77), taking diuretics (HR: 1.39; 95% CI: 1.10–1.75), antiplatelet (HR: 1.36; 95% CI: 1.05–1.76) and benzodiazepines (HR: 1.24; 95% CI: 1.00–1.53) increased risk; conversely, taking angiotensin-converting-enzyme inhibitors (HR: 0.78; 95% CI: 0.61–1.00), angiotensin-receptor-blockers (HR: 0.70; 95%CI: 0.51–0.96) and statins (HR: 0.75; 95% CI: 0.58–0.96) were associated with reduced risk. Among community-dwelling individuals, pre-existing cancer, renal and cardiac disease appeared also related with an increased risk, whereas influenza vaccination was associated with reduced risk.Conclusion:In a setting with relatively low incidence of COVID-19 across the first wave of pandemic period, increasing age, nursing-home residence and multiple comorbidities appear predisposing for COVID-19 among middle-aged/older adults. Conversely, statins, angiotensin-receptor blockers/inhibitors and influenza vaccination were related with decreased risk.(AU)

Objetivo:Analizar incidencia y riesgo/susceptibilidad de sufrir la COVID-19 en adultos según distintas condiciones médicas preexistentes. Métodos:Cohorte de base poblacional que incluyó 79.083 personas ≥50 años en Tarragona. Características basales de la cohorte (edad/sexo, comorbilidades, medicaciones crónicas) se establecieron a 01-03-2020 y se registraron todos los casos de COVID-19 confirmada ocurridos en miembros de la cohorte hasta el 30-06-2020. Para estimación de riesgos se realizó regresión de Cox, con cálculo de hazard ratio (HR) ajustados por edad, sexo y comorbilidad.Resultados:Se observaron 536 casos confirmados de COVID-19 (incidencia media: 39,5 casos por 100.000 personas-semana). En análisis multivariante, edad/años (HR: 1,01; IC el 95%: 1,00-1,02; p=0,050), estar institucionalizado/residencia (HR: 20,19; IC 95%: 15,98-25,51; p<0,001), enfermedad neurológica (HR: 1,35; IC el 95%: 1,03-1,77), diuréticos (HR: 1,39; IC 95%: 1,10-1,75), antiagregantes plaquetarios (HR: 1,36; IC 95%: 1,05-1,76) y benzodiacepinas (HR: 1,24; IC 95%: 1,00-1,53) se asociaron con un riesgo aumentado de la COVID-19 analizando la totalidad de la cohorte; contrariamente, medicación IECA (HR: 0,78; IC el 95%: 0,61-1,00), ARA-II (HR: 0,70; IC el 95%: 0,51-0,96) y estatinas (HR: 0,75; IC el 95%: 0,58-0,96) se asociaron con menor riesgo. Entre personas no institucionalizadas, cáncer, nefropatía y cardiopatía se asociaron con mayor riesgo y vacunación antigripal con menor riesgo.Conclusión:En un área con relativamente baja incidencia de COVID-19, edad, institucionalización y múltiples comorbilidades aumentaron el riesgo/susceptibilidad de sufrir la COVID-19. Contrariamente, estatinas, inhibidores del sistema renina-angiotensina y vacunación antigripal se asociaron con menor riesgo. (AU)

Susceptibility and risk of SARS-COV-2 infection among middle-aged and older adults in Tarragona area, Spain.

OBJECTIVE: To analyse susceptibility/risk of suffering COVID-19 among adults with distinct underlying medical conditions. METHODS: Population-based cohort study involving 79,083 individuals ≥50 years old in Tarragona (Southern Catalonia, Spain). Baseline cohort characteristics (demographic, pre-existing comorbidities, chronic medications and vaccinations history) were established at study start (01/03/2020) and primary outcome was laboratory-confirmed COVID-19 occurred among cohort members throughout 01/03/2020-30/06/2020. Risk of suffering COVID-19 was evaluated by Cox regression, estimating multivariable hazard ratios (HRs) adjusted for age/sex and pre-existing comorbidities. RESULTS: Across study period, 536 laboratory-confirmed COVID-19 cases were observed (mean incidence: 39.5 cases per 100,000 persons-week). In multivariable-analysis, increasing age/years (HR: 1.01; 95% CI: 1.00-1.02), nursing-home (HR: 20.19; 95% CI: 15.98-25.51), neurological disease (HR: 1.35; 95% CI: 1.03-1.77), taking diuretics (HR: 1.39; 95% CI: 1.10-1.75), antiplatelet (HR: 1.36; 95% CI: 1.05-1.76) and benzodiazepines (HR: 1.24; 95% CI: 1.00-1.53) increased risk; conversely, taking angiotensin-converting-enzyme inhibitors (HR: 0.78; 95% CI: 0.61-1.00), angiotensin-receptor-blockers (HR: 0.70; 95%CI: 0.51-0.96) and statins (HR: 0.75; 95% CI: 0.58-0.96) were associated with reduced risk. Among community-dwelling individuals, pre-existing cancer, renal and cardiac disease appeared also related with an increased risk, whereas influenza vaccination was associated with reduced risk. CONCLUSION: In a setting with relatively low incidence of COVID-19 across the first wave of pandemic period, increasing age, nursing-home residence and multiple comorbidities appear predisposing for COVID-19 among middle-aged/older adults. Conversely, statins, angiotensin-receptor blockers/inhibitors and influenza vaccination were related with decreased risk.

Evaluación a los dos meses del alta hospitalaria tras la primera ola de COVID-19: presencia de síntomas persistentes / Assessment of hospitalized covid-19 patients two month after discharge: characterization of persistent symptoms

Introduction: a series of symptoms have been reported after COVID-19, which have been encompassed in the so-named “postCOVID syndrome”. PostCOVID syndrome is a heterogeneous disorder with an uncertain pathophysiology. The aim of this study is to describe the characteristics and frequence of symptoms after COVID-19 discharge and to analyze the possible implicated factors. Methods: this is an observational propective study with COVID-19 patients hospitalized from March to April 2020. Patients were assessed in an outpatient clinic two months after discharge, and serological, radiological and laboratory workup was conducted. Previous medical history, length of stay (LOS) and intensive care unit (ICU) admission were recorded. Persistent symptons (PS) were defined as those appearing after the acute infection and present at follow-up. Results: 74 patients were included. Mean age was 66±13 years, and 54.4% patients were men. Six (8.1%) patients needed ICU admission, and median LOS was 8 (6-12) days. Forty (54.8%) patients presented PS, the most frequent being fatigue and dyspnea (20.3% each). 77% patients presented laboratory abnormalities but just in 11 cases (15.1%) were they severe. Ten (13.5%) had radiological abnormalities. 71 (95.9%) had positive IgG serology. There were no differences between patients with and without PS regarding previous medical history or acute infection course. PS patients had a higher heart rate 83 (75-93) vs 76 65-85) bpm; p=0.038) at assessment. Conclusion: symptoms and laboratory abnormalities are frequent two months after COVID-19, although usually mild. No predictors... (AU)

Introducción: se han notificado tras el alta por COVID-19 una serie de síntomas englobados dentro del llamado “síndrome post-COVID”, un cuadro heterogéneo cuya fisiopatología es incierta. Nuestro objetivo es describir las características y frecuencia de síntomas tras el alta y analizar los posibles factores relacionados. Métodos: estudio observacional prospectivo con pacientes ingresados por COVID-19 durante marzo-abril de 2020. Se evaluó en consulta a los dos meses tras el alta con valoración clínica, analítica, serología y radiografía de tórax. Se recogieron los antecedentes, la estancia hospitalaria y la necesidad de UCI. Se definieron síntomas persistentes (SP) como síntomas que aparecieron desde la infección aguda y que se mantenían al seguimiento. Resultados: se revisaron 74 pacientes. La edad media fue 66±13 años, siendo un 51,4% hombres. Seis (8,1%) ingresaron en UCI, y la mediana de estancia fue 8 (6-12) días. Cuarenta (54,8%) presentaron SP, siendo los más frecuentes astenia y disnea (20,3% ambos). Un 77% tenía alteraciones analíticas pero solo en 11 (15,1%) fueron relevantes. Diez (13,5%) presentaban alteraciones radiológicas y 71 (95,9%) tenían IgG positiva. No hubo diferencias entre los pacientes con y sin SP en sus antecedentes o evolución hospitalaria. Los pacientes con SP estaban más taquicárdicos [83 (75-93) lpm vs 76 (65-85) lpm; p=0,038], no existiendo diferencias significativas en el resto de variables... (AU)

Influence of prior comorbidities and chronic medications use on the risk of COVID-19 in adults: a population-based cohort study in Tarragona, Spain.

OBJECTIVE: To investigate possible relationships between pre-existing medical conditions (including common comorbidities and chronic medications) and risk for suffering COVID-19 disease in middle-aged and older adults. DESIGN: Population-based retrospective cohort study. SETTING: Twelve primary care centres (PCCs) in Tarragona (Spain). PARTICIPANTS: 79 083 people (77 676 community-dwelling and 1407 nursing-home residents), who were all individuals aged >50 years affiliated to the 12 participating PCCs. OUTCOMES: Baseline cohort characteristics (age, sex, vaccinations, comorbidities and chronic medications) were established at study start (1st. March 2020) and primary outcome was time to COVID-19 confirmed by PCR among cohort members throughout the epidemic period (from 1st. March 2020 to 23rd. May 2020). Risk for suffering COVID-19 was evaluated by Cox regression, estimating multivariable HRs adjusted for age, sex, comorbidities and medications use. RESULTS: During the study period, 2324 cohort members were PCR-tested, with 1944 negative and 380 positive results, which means an incidence of 480.5 PCR-confirmed COVID-19 cases per 100 000 persons-period. Assessing the total study cohort, only age (HR 1.02; 95% CI 1.01 to 1.03; p=0.002), nursing-home residence (HR 21.83; 95% CI 16.66 to 28.61; p<0.001) and receiving diuretics (HR 1.35; 95% CI 1.04 to 1.76; p=0.026) appeared independently associated with increased risk. Smoking (HR 0.62; 95% CI 0.41 to 0.93; p=0.022), ACE inhibitors (HR 0.68; 95% CI 0.47 to 0.99; p=0.046) and antihistamine (HR 0.47; 95% CI 0.22 to 1.01; p=0.052) were associated with a lower risk. Among community-dwelling individuals, cancer (HR 1.52; 95% CI 1.03 to 2.24; p=0.035), chronic respiratory disease (HR 1.82; 95% CI 1.08 to 3.07; p=0.025) and cardiac disease (HR 1.53; 95% CI 1.06 to 2.19; p=0.021) emerged to be also associated with an increased risk. Receiving ACE inhibitors (HR 0.66; 95% CI 0.44 to 0.99; p=0.046) and influenza vaccination (HR 0.63; 95% CI 0.44 to 0.91; p=0.012) was associated with decreased risk. CONCLUSION: Age, nursing-home residence and multiple comorbidities appear predisposing for COVID-19. Conversely, receiving ACE inhibitors, antihistamine and influenza vaccination could be protective, which should be closely investigated in further studies specifically focused on these concerns.

Use of distinct anti-hypertensive drugs and risk for COVID-19 among hypertensive people: A population-based cohort study in Southern Catalonia, Spain.

The use of some anti-hypertensive drugs in the current COVID-19 pandemic has become controversial. This study investigated possible relationships between anti-hypertensive medications use and COVID-19 infection risk in the ambulatory hypertensive population. This is a population-based retrospective cohort study involving 34 936 hypertensive adults >50 years in Tarragona (Southern Catalonia, Spain) who were retrospectively followed through pandemic period (from 01/03/2020 to 30/04/2020). Two data sets including demographic/clinical characteristics (comorbidities and cardiovascular medications use) and laboratory PCR codes for COVID-19 were linked to construct an anonymized research database. Cox regression was used to calculate multivariable hazard ratios (HRs) and estimate the risk of suffering COVID-19 infection. Across study period, 205 PCR-confirmed COVID-19 cases were observed, which means an overall incidence of 586.8 cases per 100 000 persons-period. In multivariable analyses, only age (HR: 1.03; 95% CI: 1.02-1.05; P < .001) and nursing home residence (HR: 19.60; 95% CI: 13.80-27.84; P < .001) appeared significantly associated with increased risk of COVID-19. Considering anti-hypertensive drugs, receiving diuretics (HR: 1.22; 95% CI: 0.90-1.67; P = .205), calcium channel blockers (HR: 1.29; 95%CI: 0.91-1.82; P = .148), beta-blockers (HR: 0.97; 95% CI: 0.68-1.37; P = .844), and angiotensin-converting enzyme inhibitors (HR: 0.83; 95% CI: 0.61-1.13; P = .238) did not significantly alter the risk of PCR-confirmed COVID-19, whereas receiving angiotensin II receptor blockers was associated with an almost statistically significant reduction risk (HR: 0.67; 95% CI: 0.44-1.01; P = .054). In conclusion, our data support that receiving renin-angiotensin-aldosterone system inhibitors does not predispose for suffering COVID-19 infection in ambulatory hypertensive people. Conversely, receiving angiotensin II receptor blockers could be related with a reduced risk.

[Evaluation of incidence and risk profile for suffering Covid-19 infection by underlying conditions among middle-aged and older adults in Tarragona.] / Evaluación de la incidencia y perfil de riesgo de Covid-19 según comorbilidad previa en adultos ≥50 años del área de Tarragona.

OBJECTIVE: Population-based data on the current Covid-19 pandemic is scarce. This study investigated incidence and risk to suffer Covid-19 by baseline underlying conditions in people ≥50 years in Tarragona region across march-april 2020. METHODS: Population-based retrospective cohort study involving 79,071 adults ≥50 years-old in Tarragona region (Southern Catalonia, Spain). Cohort characteristics (age, sex, residence, vaccinations history and comorbidities) were established at baseline, and Covid-19 cases occurring between 01/03/2020-30/04/2020 were registered. Cox regression analysis calculating Hazard ratios (HRs) adjusted by age, sex and comorbidities was used to estimate risk for Covid-19. RESULTS: Across study period, 1,547 cohort members were PCR tested (22.6% positive) and 367 were presumptive cases without PCR tested. Considering PCR-confirmed Covid-19, incidence (per 100,000 persons-period) was 441 overall (248, 141, 424, 1,303 and 3,135 in 50-59, 60-69, 70-79, 80-89 and ≥90 years-old, respectively; 380 in men and 497 in women; 259 in community-dwelling and 10,571 in nursing-home). By comorbidities, maximum incidence emerged among persons with neurological disease (2,723), atrial fibrillation (1,348), chronic renal failure (1,050), cardiac disease (856), respiratory disease (798) and diabetes (706). Lower incidence appeared in rheumatic diseases (230) and smokers (180). In multivariable analysis focused on community-dwelling individuals (N=77,671), only cardiac disease (HR: 1.47; 95% CI: 1.01-2.15; p=0.045) and respiratory disease (HR: 1.75; 95% CI: 1.00-3.02; p=0.051) were associated with an increased risk, whereas smoking (HR:0.43; 95% CI: 0.25-0.74; p=0.002) and influenza vaccinated (HR: 0.63; 95% CI: 0.43-0.92; p=0.015) appeared associated with a decreased risk. CONCLUSIONS: Apart of increasing age and nursing-home residence, chronic respiratory and cardiac disease appear at increased risk for suffering covid19. This study investigated population-based incidence of Covid-19 infection by underlying conditions among adults ≥50 years in Tarragona (Southern Catalonia, Spain) across two first months pandemic period.

OBJETIVO: Los datos clínico-epidemiológicos de base poblacional durante la actual pandemia de Covid-19 son escasos. Este estudio investigó la incidencia y riesgo de sufrir Covid-19 según condiciones basales subyacentes en la población ≥50 años de Tarragona durante marzo-abril 2020. METODOS: Estudio de cohortes retrospectivo que incluyó a 79.071 personas ≥50 años en el área de Tarragona. Se establecieron características basales de la cohorte (edad, sexo, residencia, vacunaciones y comorbilidades previas), y se registró la ocurrencia de Covid-19 entre 01/03/2020-30/04/2020. Para la estimación de riesgos se realizó regresión de Cox, con cálculo de Hazard ratios (HRs) ajustados por edad, sexo y comorbilidad. RESULTADOS: Se realizaron PCR-tests en 1.547 personas (22,6% positivos) y 367 fueron codificados como presuntos casos sin realizarse PCR-test. Considerando Covid-19 confirmada (PCR positivo), la incidencia (por 100.000 personas-periodo) fue de 441 (248, 141, 424, 1.303 y 3.135 en 50-59, 60-69, 70-79, 80-89 y ≥90 años, respectivamente; 380 en hombres frente a 497 en mujeres; 259 residentes en la comunidad respecto a 10.571 en institucionalizados). Según comorbilidades, las máximas incidencias aparecieron en enfermedad neurológica (2.723), fibrilación auricular (1.348), insuficiencia renal crónica (1.050), cardiopatía (856), enfermedad respiratoria (798) y diabetes (706). Menores incidencias aparecieron en enfermedad reumatológica (230) y fumadores (180). En personas no institucionalizadas (N=77.671), solo la enfermedad cardiaca (HR: 1,47; IC95%: 1,01-2,15; p=0,045) y respiratoria (HR: 1,75; IC95%: 1,00-3,02; p=0,051) se asociaron con incremento del riesgo, mientras que ser fumador (HR: 0,43; IC95%: 0,25-0,74; p=0,002) y vacunación antigripal en otoño previo (HR: 0,63; IC95%: 0,43-0,92; p=0,015) se asociaron con menor riesgo. CONCLUSIONES: Aparte de la edad y la institucionalización, la existencia de enfermedad respiratoria y/o cardiaca crónicas se asocia con una mayor incidencia de Covid-19 en adultos.

Evaluación de la incidencia y perfil de riesgo de Covid-19 según comorbilidad previa en adultos ≥ 50 años del área de Tarragona / Evaluation of incidence and risk profile for suffering Covid-19 infection by underlying conditions among middle-aged and older adults in Tarragona

OBJETIVO: Los datos clínico-epidemiológicos de base poblacional durante la actual pandemia de Covid-19 son escasos. Este estudio investigó la incidencia y riesgo de sufrir Covid-19 según condiciones basales subyacentes en la población ≥50 años de Tarragona durante marzo-abril 2020. MÉTODOS: Estudio de cohortes retrospectivo que incluyó a 79.071 personas ≥50 años en el área de Tarragona. Se establecieron características basales de la cohorte (edad, sexo, residencia, vacunaciones y comorbilidades previas), y se registró la ocurrencia de Covid-19 entre 01/03/2020-30/04/2020. Para la estimación de riesgos se realizó regresión de Cox, con cálculo de Hazard ratios (HRs) ajustados por edad, sexo y comorbilidad. RESULTADOS: Se realizaron PCR-tests en 1.547 personas (22,6% positivos) y 367 fueron codificados como presuntos casos sin realizarse PCR-test. Considerando Covid-19 confirmada (PCR positivo), la incidencia (por 100.000 personas-periodo) fue de 441 (248, 141, 424, 1.303 y 3.135 en 50-59, 60-69, 70-79, 80-89 y ≥90 años, respectivamente; 380 en hombres frente a 497 en mujeres; 259 residentes en la comunidad respecto a 10.571 en institucionalizados). Según comorbilidades, las máximas incidencias aparecieron en enfermedad neurológica (2.723), fibrilación auricular (1.348), insuficiencia renal crónica (1.050), cardiopatía (856), enfermedad respiratoria (798) y diabetes (706). Menores incidencias aparecieron en enfermedad reumatológica (230) y fumadores (180). En personas no institucionalizadas (N=77.671), solo la enfermedad cardiaca (HR: 1,47; IC95%: 1,01-2,15; p = 0,045) y respiratoria (HR: 1,75; IC95%: 1,00-3,02; p = 0,051) se asociaron con incremento del riesgo, mientras que ser fumador (HR: 0,43; IC95%: 0,25-0,74; p = 0,002) y vacunación antigripal en otoño previo (HR: 0,63; IC95%: 0,43-0,92; p = 0,015) se asociaron con menor riesgo. CONCLUSIONES: Aparte de la edad y la institucionalización, la existencia de enfermedad respiratoria y/o cardiaca crónicas se asocia con una mayor incidencia de Covid-19 en adultos

OBJECTIVE: Population-based data on the current Covid-19 pandemic is scarce. This study investigated incidence and risk to suffer Covid-19 by baseline underlying conditions in people ≥50 years in Tarragona region across march-april 2020. METHODS: Population-based retrospective cohort study involving 79,071 adults ≥50 years-old in Tarragona region (Southern Catalonia, Spain). Cohort characteristics (age, sex, residence, vaccinations history and comorbidities) were established at baseline, and Covid-19 cases occurring between 01/03/2020-30/04/2020 were registered. Cox regression analysis calculating Hazard ratios (HRs) adjusted by age, sex and comorbidities was used to estimate risk for Covid-19. RESULTS: Across study period, 1,547 cohort members were PCR tested (22.6% positive) and 367 were presumptive cases without PCR tested. Considering PCR-confirmed Covid-19, incidence (per 100,000 persons-period) was 441 overall (248, 141, 424, 1,303 and 3,135 in 50-59, 60-69, 70-79, 80-89 and ≥90 years-old, respectively; 380 in men and 497 in women; 259 in community-dwelling and 10,571 in nursing-home). By comorbidities, maximum incidence emerged among persons with neurological disease (2,723), atrial fibrillation (1,348), chronic renal failure (1,050), cardiac disease (856), respiratory disease (798) and diabetes (706). Lower incidence appeared in rheumatic diseases (230) and smokers (180). In multivariable analysis focused on community-dwelling individuals (N=77,671), only cardiac disease (HR: 1.47; 95% CI: 1.01-2.15; p = 0.045) and respiratory disease (HR: 1.75; 95% CI: 1.00-3.02; p = 0.051) were associated with an increased risk, whereas smoking (HR:0.43; 95% CI: 0.25-0.74; p = 0.002) and influenza vaccinated (HR: 0.63; 95% CI: 0.43-0.92; p = 0.015) appeared associated with a decreased risk. CONCLUSIONS: Apart of increasing age and nursing-home residence, chronic respiratory and cardiac disease appear at increased risk for suffering covid19. This study investigated population-based incidence of Covid-19 infection by underlying conditions among adults ≥50 years in Tarragona (Southern Catalonia, Spain) across two first months pandemic period

Multiple myeloma in elderly patients-a Portuguese multicentric real-life study.

Patients older than 75 years old with multiple myeloma (MM) have shorter survival and are usually treated differently from what features in clinical trials. In this study, the authors characterized the Portuguese population of MM patients above 75 years old, treated between 2009 and 2016. We compared the outcomes obtained with bortezomib-based protocols (BBP), thalidomide-based protocols (TBP), and chemotherapy (CT) using univariate and multivariate controlling for age, performance status, International Staging System score, renal impairment, and number of comorbidities. We retrieved data from 386 patients, treated in 12 hospitals. Three hundred thirty-one cases were analyzed: 119 patients treated with BBP, 65 with TBP, 147 with CT. Median age was 79 years; CT-treated patients were older, had a worse performance status, and have more comorbidities. The median follow-up was 25 months. The 2-year OS was 58% and the median OS was 29.5 months. Patients treated with BBP had more frequently very good partial response (VGPR) or better response, and the subgroup of more fit patients had a significantly longer progression-free survival (PFS) and OS. The most frequently grade 3-4 toxicities were hematologic, infectious, and neurologic and were significantly lower in TBP and CT groups vs BBP. The most common second line was CT, followed by lenalidomide. Patients treated with lenalidomide had a higher probability of VGPR or better and a superior 1-year PFS. Despite the limitations of a retrospective study, our cohort represents the reality of older patients with MM in a western country. The hazard of death or progression was higher for old, fit patients treated, in first line, with CT and with TBP compared with that of BBP.

Once- versus twice-daily dosing of eliglustat in adults with Gaucher disease type 1: The Phase 3, randomized, double-blind EDGE trial.

Eliglustat is a first-line oral therapy for adults with Gaucher disease type 1 (GD1) with compatible CYP2D6-metabolizer phenotypes (>90% of patients). The randomized, double-blind EDGE trial (NCT01074944, Sanofi Genzyme) evaluated once-daily eliglustat dosing compared with the approved twice-daily regimen at the same total daily dose in adults with GD1. Subjects received twice-daily dosing during a 6- to 18-month lead-in period. Only subjects who attained prespecified treatment goals for hemoglobin, platelet count, spleen and liver volumes, and bone symptoms during the lead-in period were randomized to once- or twice-daily dosing. Of 170 enrolled patients, 156 completed the lead-in period and 131 met all requirements to enter the double-blind treatment period. To achieve the composite primary endpoint in the double-blind period, patients had to maintain clinical stability relative to baseline on all five endpoints (hemoglobin, platelet count, spleen and liver volumes, and bone symptoms) and meet pharmacokinetic and other tolerability requirements as determined by the investigator after 1year of eliglustat treatment. After 1year, 80.4% (95% CI: 67.6, 89.8) of once-daily patients were stable compared with 83.1% (95% CI: 71.0, 91.6) of twice-daily patients. The 95% CI for the mean difference of -2.7% between groups was -17.7, 11.9. Because the lower bound of the CI exceeded the pre-defined non-inferiority margin of -15%, once-daily dosing could not be declared non-inferior to twice-daily dosing. Both once-daily and twice-daily patients maintained mean values for hematologic and visceral measures within established therapeutic goals during the double-blind treatment and long-term extension periods. Eliglustat was generally well-tolerated during this long-term trial (mean treatment duration: 3.3years), with just four withdrawals (2%) for related adverse events (AE), and similar AE profiles for both dosing regimens. Patients on twice-daily eliglustat showed more stability overall, and this dose regimen was better tolerated, confirming the dosing regimen for most patients specified in the drug label.

Management and monitoring recommendations for the use of eliglustat in adults with type 1 Gaucher disease in Europe.

PURPOSE: In Gaucher disease, diminished activity of the lysosomal enzyme, acid ß-glucosidase, leads to accumulation of glucosylceramides and related substrates, primarily in the spleen, liver, and bone marrow. Eliglustat is an oral substrate reduction therapy approved in the European Union and the United States as a first-line treatment for adults with type 1 Gaucher disease who have compatible CYP2D6 metabolism phenotypes. A European Advisory Council of experts in Gaucher disease describes the characteristics of eliglustat that are distinct from enzyme augmentation therapy (the standard of care) and miglustat (the other approved substrate reduction therapy) and recommends investigations and monitoring for patients on eliglustat therapy within the context of current recommendations for Gaucher disease management. RESULTS: Eliglustat is a selective, potent inhibitor of glucosylceramide synthase, the enzyme responsible for biosynthesis of glucosylceramides which accumulate in Gaucher disease. Extensive metabolism of eliglustat by CYP2D6, and, to a lesser extent, CYP3A of the cytochrome P450 pathway, necessitates careful consideration of the patient's CYP2D6 metaboliser status and use of concomitant medications which share metabolism by these pathways. Guidance on specific assessments and monitoring required for eliglustat therapy, including an algorithm to determine eligibility for eliglustat, are provided. CONCLUSIONS: As a first-line therapy for type 1 Gaucher disease, eliglustat offers eligible patients a daily oral therapy alternative to biweekly infusions of enzyme therapy. Physicians will need to carefully assess individual Gaucher patients to determine their appropriateness for eliglustat therapy. The therapeutic response to eliglustat and use of concomitant medications will require long-term monitoring.

Carriers of the Complex Allele HFE c.[187C>G;340+4T>C] Have Increased Risk of Iron Overload in São Miguel Island Population (Azores, Portugal).

Iron overload is associated with acquired and genetic conditions, the most common being hereditary hemochromatosis (HH) type-I, caused by HFE mutations. Here, we conducted a hospital-based case-control study of 41 patients from the São Miguel Island (Azores, Portugal), six belonging to a family with HH type-I pseudodominant inheritance, and 35 unrelated individuals fulfilling the biochemical criteria of iron overload compatible with HH type-I. For this purpose, we analyzed the most common HFE mutations- c.845G>A [p.Cys282Tyr], c.187C>G [p.His63Asp], and c.193A>T [p.Ser65Cys]. Results revealed that the family's HH pseudodominant pattern is due to consanguineous marriage of HFE-c.845G>A carriers, and to marriage with a genetically unrelated spouse that is a -c.187G carrier. Regarding unrelated patients, six were homozygous for c.845A, and three were c.845A/c.187G compound heterozygous. We then performed sequencing of HFE exons 2, 4, 5 and their intron-flanking regions. No other mutations were observed, but we identified the -c.340+4C [IVS2+4C] splice variant in 26 (74.3%) patients. Functionally, the c.340+4C may generate alternative splicing by HFE exon 2 skipping and consequently, a protein missing the α1-domain essential for HFE/ transferrin receptor-1 interactions. Finally, we investigated HFE mutations configuration with iron overload by determining haplotypes and genotypic profiles. Results evidenced that carriers of HFE-c.187G allele also carry -c.340+4C, suggesting in-cis configuration. This data is corroborated by the association analysis where carriers of the complex allele HFE-c.[187C>G;340+4T>C] have an increased iron overload risk (RR = 2.08, 95% CI = 1.40-2.94, p<0.001). Therefore, homozygous for this complex allele are at risk of having iron overload because they will produce two altered proteins--the p.63Asp [c.187G], and the protein lacking 88 amino acids encoded by exon 2. In summary, we provide evidence that the complex allele HFE-c.[187C>G;340+4T>C] has a role, as genetic predisposition factor, on iron overload in the São Miguel population. Independent replication studies in other populations are needed to confirm this association.