Inflammatory and Cardiovascular Biomarkers to Monitor Fabry Disease Progression.

Fabry disease is an invalidating multisystemic disorder affecting α-Galactosidase, a rate-limiting hydrolase dedicated to lipid catabolism. Non-metabolized substrates, such as Globotriaosylceramide and its derivatives trigger the direct or indirect activation of inflammatory events and endothelial dysfunction. In spite of the efficacy demonstrated by enzyme replacement therapy or pharmacological chaperones in delaying disease progression, few studies have analyzed whether these treatments can improve the pro-inflammatory state of FD patients. Therefore, the aim of this work was to assess cytokines and cardiovascular risk-related proteins detectable in plasma from FD patients, whether treated or not with ERT, to evaluate the reliability of these markers in monitoring disease stage and treatment effects. We identified inflammatory and endothelial dysfunction markers (ADAMTS-13, TNF-α, GDF-15, MIP-1ß, VEGFA, MPO, and MIC-1) that cooperate in a common pathway and are increased in FD patients' plasma samples. As shown by the assessment of these proteins over time, they can help to evaluate the risk of higher severity in FD, as well as ERT effects. Even though the analyzed proteins cannot be considered as proper biomarkers due to their non-specificity to FD, taken together they can provide a signature of reference molecules with prognostic value for early diagnosis, and evaluation of disease progression and treatment efficacy, using blood samples.

Characterization of the plasma proteomic profile of Fabry disease: Potential sex- and clinical phenotype-specific biomarkers.

Fabry disease (FD) is a X-linked rare lysosomal storage disorder caused by deficient α-galactosidase A (α-GalA) activity. Early diagnosis and the prediction of disease course are complicated by the clinical heterogeneity of FD, as well as by the frequently inconclusive biochemical and genetic test results that do not correlate with clinical course. We sought to identify potential biomarkers of FD to better understand the underlying pathophysiology and clinical phenotypes. We compared the plasma proteomes of 50 FD patients and 50 matched healthy controls using DDA and SWATH-MS. The >30 proteins that were differentially expressed between the 2 groups included proteins implicated in processes such as inflammation, heme and haemoglobin metabolism, oxidative stress, coagulation, complement cascade, glucose and lipid metabolism, and glycocalyx formation. Stratification by sex revealed that certain proteins were differentially expressed in a sex-dependent manner. Apolipoprotein A-IV was upregulated in FD patients with complications, especially those with chronic kidney disease, and apolipoprotein C-III and fetuin-A were identified as possible markers of FD with left ventricular hypertrophy. All these proteins had a greater capacity to identify the presence of complications in FD patients than lyso-GB3, with apolipoprotein A-IV standing out as being more sensitive and effective in differentiating the presence and absence of chronic kidney disease in FD patients than renal markers such as creatinine, glomerular filtration rate and microalbuminuria. Identification of these potential biomarkers can help further our understanding of the pathophysiological processes that underlie the heterogeneous clinical manifestations associated with FD.

Genetic and clinical characterization of a novel FH founder mutation in families with hereditary leiomyomatosis and renal cell cancer syndrome.

BACKGROUND: Hereditary leiomyomatosis and renal cell cancer syndrome is a rare autosomal dominant hereditary syndrome. Previously, we published the largest cohort of FH mutation carriers in Spain and observed a highly recurrent missense heterozygous variant, FH(NM_000143.4):c.1118A > G p.(Asn373Ser), in 104 individuals from 31 apparently unrelated families. Here, we aimed to establish its founder effect and characterize the associated clinical phenotype. RESULTS: Haplotype analysis confirmed that families shared a common haplotype (32/38 markers) spanning 0.61-0.82 Mb, indicating this recurrent variant was inherited from a founder ancestor. Cutaneous and uterine leiomyomatosis were diagnosed in 64.6% (64/99) and 98% (50/51) of patients, respectively, and renal cell cancer was present in 10.4% (10/96). The pathogenic FH_c.1118A > G variant is a Spanish founder mutation that originated 12-26 generations ago. We estimate that the variant may have appeared between 1370 and 1720. Individuals carrying this founder mutation had similar frequency of renal cell cancer and a higher frequency of renal cysts and leiomyomas than those in other cohorts of this syndrome. CONCLUSIONS: In the Spanish province of Alicante there is a high prevalence of HLRCC because of the founder mutation FH c.1118A > G; p.(Asn373Ser). The characterization of founder mutations provides accurate and specific information regarding their penetrance and expressivity. In individuals with suspected HLRCC from the province of Alicante, genetic testing by direct analysis of the founder FH c.1118A > G; p.(Asn373Ser) mutation may be a faster and more efficient diagnostic tool compared with complete gene sequencing.

Severe Spontaneous Hematomas in Patients Hospitalized with COVID-19.

Objective: To describe the epidemiological, clinical, laboratory, and radiological characteristics, medical treatment, and outcomes of a case series of severe spontaneous hematoma in COVID-19. Material and Methods. This retrospective study included patients hospitalized for COVID-19 who were diagnosed with severe spontaneous bleeding complications by following a standardized treatment protocol that included computed tomography angiography (CTA) from 1 March 2020 to 28 February 2022. The main outcomes were embolization and all-cause mortality. Baseline variables were analyzed for their association with mortality using bivariable logistic regression, and results were expressed as odds ratios (OR) and 95% confidence intervals (CI). Results: In total, 2450 adults were hospitalized for COVID-19 in our center during the study period. 20 patients presented severe and spontaneous intramuscular bleeding (8.1 per 1000 COVID-19 admission vs. 0.47 per 1000 non-COVID-19 admissions, p < 0.001); their median age was 68.5 years (interquartile range (IQR) 63, 80), they had high comorbidity (median Charlson comorbidity index 4.5), and 95% were receiving high doses of heparin. The median interval from COVID-19 symptoms to bleeding was 17 days (IQR 13, 24), and 70% reported cough as a previous symptom. Hypovolemic shock, hypotension, and abdominal pain were the most frequent symptoms of the hematoma. All presented decreased hemoglobin, and 95% required transfusion. Intramuscular hematoma occurred most frequently in the rectus sheath, iliopsoas compartment, and femoral-iliac compartment. All patients underwent embolization; mortality was 45%. We did not identify risk factors associated with an increased risk of death. Conclusion: Although severe bleeding is an uncommon complication of COVID-19, its prevalence is higher than in inpatients without COVID-19, it usually needs embolization, and it is associated with high mortality.

Association between Clinical Frailty Scale (CFS) and clinical presentation and outcomes in older inpatients with COVID-19.

BACKGROUND: Frailty is a physiological condition characterized by a decreased reserve to stressors. In patients with COVID-19, frailty is a risk factor for in-hospital mortality. The aim of this study was to assess the relationship between clinical presentation, analytical and radiological parameters at admission, and clinical outcomes according to frailty, as defined by the Clinical Frailty Scale (CFS), in old people hospitalized with COVID-19. MATERIALS AND METHODS: This retrospective cohort study included people aged 65 years and older and admitted with community-acquired COVID-19 from 3 March 2020 to 31 April 2021. Patients were categorized using the CFS. Primary outcomes were symptoms of COVID-19 prior to admission, mortality, readmission, admission in intensive care unit (ICU), and need for invasive mechanical ventilation. Analysis of clinical symptoms, clinical outcomes, and CFS was performed using multivariable logistic regression, and results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of the 785 included patients, 326 (41.5%, 95% CI 38.1%-45.0%) were defined as frail (CFS ≥ 5 points): 208 (26.5%, 95% CI 23.5%-29.7%) presented mild-moderate frailty (CFS 5-6 points) and 118 (15.0%, 95% CI 12.7%-17.7%), severe frailty (7-9 points). After adjusting for epidemiological variables (age, gender, residence in a nursing home, and Charlson comorbidity index), frail patients were significantly less likely to present dry cough (OR 0.58, 95% CI 0.40-0.83), myalgia-arthralgia (OR 0.46, 95% CI 0.29-0.75), and anosmia-dysgeusia (OR 0.46, 95% CI 0.23-0.94). Confusion was more common in severely frail patients (OR 3.14; 95% CI 1.64-5.97). After adjusting for epidemiological variables, the risk of in-hospital mortality was higher in frail patients (OR 2.79, 95% CI 1.79-4.25), including both those with mild-moderate frailty (OR 1.98, 95% CI 1.23-3.19) and severe frailty (OR 5.44, 95% CI 3.14-9.42). Readmission was higher in frail patients (OR 2.11, 95% CI 1.07-4.16), but only in mild-moderate frailty (OR 2.35, 95% CI 1.17-4.75).. CONCLUSION: Frail patients presented atypical symptoms (less dry cough, myalgia-arthralgia, and anosmia-dysgeusia, and more confusion). Frailty was an independent predictor for death, regardless of severity, and mild-moderate frailty was associated with readmission.

Current clinical spectrum of common variable immunodeficiency in Spain: The multicentric nationwide GTEM-SEMI-CVID registry.

Common variable immunodeficiency (CVID) constitutes a heterogenic group of primary immunodeficiency disorders with a wide-ranging clinical spectrum. CVID-associated non-infectious morbidity constitutes a major challenge requiring a full understanding of its pathophysiology and its clinical importance and global variability, especially considering the broad clinical, genetic, and regional heterogeneity of CVID disorders. This work aimed to develop a nationwide, multicenter, retrospective study over a 3-year period describing epidemiological, clinical, laboratory, therapeutic, and prognostic features of 250 CVID patients in Spain. The mean diagnostic delay was around 10 years and most patients initially presented with infectious complications followed by non-infectious immune disorders. However, infectious diseases were not the main cause of morbimortality. Non-infectious lung disease was extraordinarily frequent in our registry affecting approximately 60% of the patients. More than one-third of the patients in our cohort showed lymphadenopathies and splenomegaly in their follow-up, and more than 33% presented immune cytopenias, especially Evans' syndrome. Gastrointestinal disease was observed in more than 40% of the patients. Among biopsied organs in our cohort, benign lymphoproliferation was the principal histopathological alteration. Reaching 15.26%, the global prevalence of cancer in our registry was one of the highest reported to date, with non-Hodgkin B lymphoma being the most frequent. These data emphasize the importance of basic and translational research delving into the pathophysiological pathways involved in immune dysregulation and diffuse lymphocytic infiltration. This would reveal new tailored strategies to reduce immune complications, and the associated healthcare burden, and ensure a better quality of life for CVID patients.

Pathological Findings Associated With SARS-CoV-2 on Postmortem Core Biopsies: Correlation With Clinical Presentation and Disease Course.

Background: Autopsies can shed light on the pathogenesis of new and emerging diseases. Aim: To describe needle core necropsy findings of the lung, heart, and liver in decedents with COVID-19. Material: Cross-sectional study of needle core necropsies in patients who died with virologically confirmed COVID-19. Histopathological analyses were performed, and clinical data and patient course evaluated. Results: Chest core necropsies were performed in 71 decedents with a median age of 81 years (range 52-97); 47 (65.3%) were men. The median interval from symptoms onset to death was 17.5 days (range 1-84). Samples of lung (n = 62, 87.3%), heart (n = 48, 67.6%) and liver (n = 39, 54.9%) were obtained. Fifty-one lung samples (82.3%) were abnormal: 19 (30.6%) showed proliferative diffuse alveolar damage (DAD), 12 (19.4%) presented exudative DAD, and 10 (16.1%) exhibited proliferative plus exudative DAD. Of the 46 lung samples tested for SARS-CoV-19 by RT-PCR, 39 (84.8%) were positive. DAD was associated with premortem values of lactate dehydrogenase of 400 U/L or higher [adjusted odds ratio (AOR) 21.73; 95% confidence interval (CI) 3.22-146] and treatment with tocilizumab (AOR 6.91; 95% CI 1.14-41.7). Proliferative DAD was associated with an onset-to-death interval of over 15 days (AOR 7.85, 95% CI 1.29-47.80). Twenty-three of the 48 (47.9%) heart samples were abnormal: all showed fiber hypertrophy, while 9 (18.8%) presented fibrosis. Of the liver samples, 29/39 (74.4%) were abnormal, due to steatosis (n = 12, 30.8%), cholestasis (n = 6, 15.4%) and lobular central necrosis (n = 5, 12.8%). Conclusion: Proliferative DAD was the main finding on lung core needle necropsy in people who died from COVID-19; this finding was related to a longer disease course. Changes in the liver and heart were common.

Bacteraemia and quick Sepsis Related Organ Failure Assessment (qSOFA) are independent risk factors for long-term mortality in very elderly patients with suspected infection: retrospective cohort study.

BACKGROUND: In older adult patients, bloodstream infections cause significant mortality. However, data on long-term prognosis in very elderly patients are scarce. This study aims to assess 1-year mortality from bacteraemia in very elderly patients. METHODS: Retrospective cohort study in inpatients aged 80 years or older and suspected of having sepsis. Patients with (n = 336) and without (n = 336) confirmed bacteraemia were matched for age, sex, and date of culture, and their characteristics were compared. All-cause mortality and risk of death were assessed using the adjusted hazard ratio (aHR). RESULTS: Compared to controls, cases showed a higher 1-year mortality (34.8% vs. 45.2%) and mortality rate (0.46 vs. 0.69 deaths per person-year). Multivariable analysis showed significant risk of 1-year mortality in patients with bacteraemia (aHR: 1.31, 95% confidence interval [CI] 1.03-1.67), quick Sepsis Related Organ Failure Assessment (qSOFA) score of 2 or more (aHR: 2.71, 95% CI 2.05-3.57), and age of 90 years or older (aHR 1.53, 95% CI 1.17-1.99). CONCLUSIONS: In elderly patients suspected of sepsis, bacteraemia is associated with a poor prognosis and higher long-term mortality. Other factors related to excess mortality were age over 90 years and a qSOFA score of 2 or more.

[Valproic Acid Could Help in the Fight Against COVID-19: a case-control study]. / El ácido valproico podría ayudar en la lucha contra el COVID-19: un estudio de casos y controles.

OBJECTIVE: There is early evidence about Valproic acid (VPA) antiviral effect. Our aim was to investigate the incidence and severity of SARS-CoV-2 infection in VPA users as compared with the general population. MATERIAL AND METHODS: A case-control study nested within a cohort, carried out between March 1 and December 17, 2020. Retrospectively, we identified confirmed SARS-CoV-2 infection patients exposed to VPA in our health department (defined as case). We ascertained VPA regimen (all the time (AT)(292 days) or at least 20% of the study period (notAT)(≥58 days) and if VPA levels were in therapeutic range (ATR) (50-100 mcg/mL) in the last 24 months. We calculated the cumulative incidence of SARS-CoV-2 infection and hospital admission in the cases, comparing it with the general unexposed VPA population (controls). RESULTS: During the study period, 6183 PCR+ were detected among 281035 inhabitants, of these, 746 were hospitalized. 691 patients were on VPA notAT and 628 (90.1%) AT. The indication for VPA use was epilepsy in 54.9%. The incidence of PCR+ was 1.736 % (OR 0.785 (95%CI 0.443-1.390) and 1.910 % (OR 0.865 (95%CI 0.488-1.533), on VPA notAT and VPA AT patients, respectively vs. 2.201% in people without VPA regimen. Those patients with VPA ATR had a lower risk of PCR + (OR 0.233 (95%CI 0.057-0.951) notAT; OR 0.218 (95%CI 0.053-0.890) AT). Hospital admission incidence was lower in patient on VPA (OR was 0.543 (95% CI 0.076 to 3.871). CONCLUSION: Patients with VPA within the therapeutic range had a reduction of SARS-Cov-2 infection incidence greater than 75%. There is a downward trend in the risk of COVID-19 admission by SARS-CoV-2 in patients on VPA therapy. These findings warrant further investigation.

Hospitalized patients with breakthrough COVID-19: Clinical features and poor outcome predictors.

OBJECTIVES: To describe breakthrough COVID-19 infection in patients who needed hospitalization and the factors associated with poor outcomes. METHODS: We conducted a retrospective study on patients hospitalized with COVID-19 between December 27, 2020, and October 17, 2021, with either a complete vaccination (CV) scheme (diagnosed 2 weeks after the second dose of the Pfizer/Moderna/AstraZeneca or first dose of the Janssen vaccine was administered) or a partial vaccination (PV) scheme. The main outcomes were all-cause mortality and the need for invasive mechanical ventilation (IMV). The baseline factors associated with the outcomes were analyzed by multiple logistic regression to estimate the odds ratios (odds ratio [OR]; 95% confidence interval [CI]). RESULTS: A total of 145 (101 CV) patients were included. The CV subgroup was mainly composed of older males with high comorbidity (Charlson Index ≥3, 72%; immunosuppression, 20%) and with bilateral pneumonia in 63.4%. Limited therapeutic effort (LTE) was agreed upon for 28% of the patients. In the CV subgroup, endotracheal intubation was required in 10.9% of patients, reaching 15.3% when excluding LTE patients; the global mortality was 22.8%, reaching 41.4% in the subgroup with LTE. Although the patients with PV were younger and had fewer comorbidities, the main outcomes did not differ significantly between the CV and PV groups. The predictors of poor outcomes were age ≥ 65 years, confusion, ferritin > 500 mg/L, extensive lung infiltrates, and a Charlson Index ≥ 3. CONCLUSIONS: Patients with CV hospitalized because of breakthrough COVID-19 infection tend to be older persons, with comorbidities, and have a high mortality.

Nasopharyngeal Microbiota as an early severity biomarker in COVID-19 hospitalised patients.

This study aimed to analyse the diversity and taxonomic composition of the nasopharyngeal microbiota, to determine its association with COVID-19 clinical outcome. To study the microbiota, we utilized 16S rRNA sequencing of 177 samples that came from a retrospective cohort of COVID-19 hospitalized patients. Raw sequences were processed by QIIME2. The associations between microbiota, invasive mechanical ventilation (IMV), and all-cause mortality were analysed by multiple logistic regression, adjusted for age, gender, and comorbidity. The microbiota α diversity indexes were lower in patients with a fatal outcome, whereas the ß diversity analysis showed a significant clustering in these patients. After multivariate adjustment, the presence of Selenomonas spp., Filifactor spp., Actinobacillus spp., or Chroococcidiopsis spp., was associated with a reduction of more than 90% of IMV. Higher diversity and the presence of certain genera in the nasopharyngeal microbiota seem to be early biomarkers of a favourable clinical evolution in hospitalized COVID-19 patients.

Palliative Sedation in COVID-19 End-of-Life Care. Retrospective Cohort Study.

Background and Objectives: Descriptions of end-of-life in COVID-19 are limited to small cross-sectional studies. We aimed to assess end-of-life care in inpatients with COVID-19 at Alicante General University Hospital (ALC) and compare differences according to palliative and non-palliative sedation. Material and Methods: This was a retrospective cohort study in inpatients included in the ALC COVID-19 Registry (PCR-RT or antigen-confirmed cases) who died during conventional admission from 1 March to 15 December 2020. We evaluated differences among deceased cases according to administration of palliative sedation. Results: Of 747 patients evaluated, 101 died (13.5%). Sixty-eight (67.3%) died in acute medical wards, and 30 (44.1%) received palliative sedation. The median age of patients with palliative sedation was 85 years; 44% were women, and 30% of cases were nosocomial. Patients with nosocomial acquisition received more palliative sedation than those infected in the community (81.8% [9/11] vs 36.8% [21/57], p = 0.006), and patients admitted with an altered mental state received it less (20% [6/23] vs. 53.3% [24/45], p = 0.032). The median time from admission to starting palliative sedation was 8.5 days (interquartile range [IQR] 3.0-14.5). The main symptoms leading to palliative sedation were dyspnea at rest (90%), pain (60%), and delirium/agitation (36.7%). The median time from palliative sedation to death was 21.8 h (IQR 10.4-41.1). Morphine was used in all palliative sedation perfusions: the main regimen was morphine + hyoscine butyl bromide + midazolam (43.3%). Conclusions: End-of-life palliative sedation in patients with COVID-19 was initiated quite late. Clinicians should anticipate the need for palliative sedation in these patients and recognize the breathlessness, pain, and agitation/delirium that foreshadow death.

Clinical Frailty Score vs Hospital Frailty Risk Score for predicting mortality and other adverse outcome in hospitalised patients with COVID-19: Spanish case series.

OBJECTIVES: Frailty can be used as a predictor of adverse outcomes in people with coronavirus disease 2019 (COVID-19). The aim of the study was to analyse the prognostic value of two different frailty scores in patients hospitalised for COVID-19. MATERIAL AND METHODS: This retrospective cohort study included adult (≥18 years) inpatients with COVID-19 and took place from 3 March to 2 May 2020. Patients were categorised by Clinical Frailty Score (CFS) and Hospital Frailty Risk Score (HFRS). The primary outcome was in-hospital mortality, and secondary outcomes were tocilizumab treatment, length of hospital stay, admission in intensive care unit (ICU) and need for invasive mechanical ventilation. Results were analysed by multivariable logistic regression and expressed as odds ratios (ORs), adjusting for age, sex, kidney function and comorbidity. RESULTS: Of the 290 included patients, 54 were frail according to the CFS (≥5 points; prevalence 18.6%, 95% confidence interval [CI]: 14.4-23.7) vs 65 by HFRS (≥5 points; prevalence: 22.4%, 95% CI 17.8-27.7). Prevalence of frailty increased with age according to both measures: 50-64 years, CFS 1.9% vs HFRS 12.3%; 65-79 years, CFS 31.5% vs HFRS 40.0%; and ≥80 years, CFS 66.7% vs HFRS 40.0% (P < .001). CFS-defined frailty was independently associated with risk of death (OR 3.67, 95% CI 1.49-9.04) and less treatment with tocilizumab (OR 0.28, 95% CI 0.08-0.93). HFRS-defined frailty was independently associated with length of hospital stay over 10 days (OR 2.89, 95% CI 1.53-5.44), ICU admission (OR 4.18, 95% CI 1.84-9.52) and invasive mechanical ventilation (OR 5.93, 95% CI 2.33-15.10). CONCLUSION: In the spring 2020 wave of the COVID-19 pandemic in Spain, CFS-defined frailty was an independent predictor for death, while frailty as measured by the HFRS was associated with length of hospital stay over 10 days, ICU admission and use of invasive mechanical ventilation.

Effectivity of a Program for the Control and Prevention of COVID-19 Healthcare-Associated Infections in a Spanish Academic Hospital.

BACKGROUND: Although recommendations to prevent COVID-19 healthcare-associated infections (HAIs) have been proposed, data on their effectivity are currently limited. OBJECTIVE: The aim was to evaluate the effectivity of a program of control and prevention of COVID-19 in an academic general hospital in Spain. METHODS: We captured the number of COVID-19 cases and the type of contact that occurred in hospitalized patients and healthcare personnel (HCP). To evaluate the impact of the continuous use of a surgical mask among HCP, the number of patients with COVID-19 HAIs and accumulated incidence of HCP with COVID-19 was compared between the preintervention and intervention periods. RESULTS: Two hundred fifty-two patients with COVID-19 have been admitted to the hospital. Seven of them had an HAI origin (6 in the preintervention period and 1 in the intervention period). One hundred forty-two HCP were infected with SARS-CoV-2. Of them, 22 (15.5%) were attributed to healthcare (2 in the emergency department and none in the critical care departments), and 120 (84.5%) were attributed to social relations in the workplace or during their non-work-related personal interactions. The accumulated incidence during the preintervention period was 22.3 for every 1000 HCP and 8.2 for every 1000 HCP during the intervention period. The relative risk was 0.37 (95% confidence interval, 0.25 to 0.55) and the attributable risk was -0.014 (95% confidence interval, -0.020 to -0.009). CONCLUSIONS: A program of control and prevention of HAIs complemented with the recommendation for the continuous use of a surgical mask in the workplace and social environments of HCP effectively decreased the risk of COVID-19 HAIs in admitted patients and HCP.

Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disease with autosomal dominant inheritance. Disease-causing variants in endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1) genes are detected in more than 90% of cases submitted to molecular diagnosis. METHODS: We used data from the RiHHTa (Computerized Registry of Hereditary Hemorrhagic Telangiectasia) registry to describe genetic variants and to assess their genotype-phenotype correlation among HHT patients in Spain. RESULTS: By May 2019, 215 patients were included in the RiHHTa registry with a mean age of 52.5 ± 16.5 years and 136 (63.3%) were women. Definitive HHT diagnosis defined by the Curaçao criteria were met by 172 (80%) patients. Among 113 patients with genetic test, 77 (68.1%) showed a genetic variant in ACVRL1 and 36 (31.8%) in ENG gene. The identified genetic variants in ACVRL1 and ENG genes and their clinical significance are provided. ACVRL1 mutations were more frequently nonsense (50%) while ENG mutations were more frequently, frameshift (39.1%). ENG patients were significantly younger at diagnosis (36.9 vs 45.7 years) and had pulmonary arteriovenous malformations (AVMs) (71.4% vs 24.4%) and cerebral AVMs (17.6% vs 2%) more often than patients with ACVRL1 variants. Patients with ACVRL1 variants had a higher cardiac index (2.62 vs 3.46), higher levels of hepatic functional blood tests, and anemia (28.5% vs 56.7%) more often than ENG patients. CONCLUSIONS: ACVRL1 variants are more frequent than ENG in Spain. ACVRL1 patients developed symptomatic liver disease and anemia more often than ENG patients. Compared to ACVRL1, those with ENG variants are younger at diagnosis and show pulmonary and cerebral AVMs more frequently.

The quick Sepsis-related Organ Failure Assessment (qSOFA) is a good predictor of in-hospital mortality in very elderly patients with bloodstream infections: A retrospective observational study.

People over 80 years old are now the fastest-growing age group. Bloodstream infections (BSI) in these patients may present with specific characteristics. The objective of this study was to analyze independent factors affecting in-hospital mortality (IHM) due to BSI in very elderly patients (≥80 years of age) and to compare the clinical presentation of BSI in patients aged 80-89 years versus those aged 90 or more. Retrospective, cross-sectional and observational study of BSI in patients aged 80 years or older. The study used IHM as the primary outcome. Stepwise multiple logistic regression models were used to identify associations between potential predictors and IHM. Of the 336 included patients, 76.8% (n = 258) were in the 80-89-year age group and 23.2% (n = 78) in the 90+ age group; 17.3% (n = 58) of patients died during admission. This outcome was independently associated with quick Sepsis Related Organ Failure Assessment (qSOFA) of 2 or more (adjusted odds ratio [aOR] 4.7, 95% confidence interval [CI] 2.3-9.4; p < 0.001). Other predictors included an origin of BSI outside the urinary tract (aOR 5.5, 95% CI 2.4-12.6; p < 0.001), thrombocytopenia (aOR 4.9, 95% CI 1.8-13.4; p = 0.002), hospital-acquired infection (aOR 3.0, 95% CI 1.2-7.5; p = 0.015), and inappropriate empiric antibiotics (aOR 2.0, 95% CI 1.1-3.9; p = 0.04). IHM was 23.1% in the 90+ age group and 15.5% in patients aged 80 to 89 (p = 0.012). However, the 90+ age group was more likely to have a score of at least 2 on the qSOFA (29.9% vs. 19.1%, p = 0.043) and Pitt bacteremia scales (44.9% vs. 30.2%; p = 0.02), as well as chronic kidney disease (56.4% vs. 36.0%; p = 0.001) and altered mental state (40.3% vs. 25.7%; p = 0.013). In conclusion: A qSOFA score of 2 or more and a BSI originating outside the urinary tract were independent predictors of IHM. The 90+ age group was at higher risk than the 80-89-year age group of having a qSOFA score and Pitt bacteremia score of 2 or more as well as an altered mental state.

Seasonal influenza in octogenarians and nonagenarians admitted to a general hospital: epidemiology, clinical presentation and prognostic factors / Gripe estacional en octogenarios y nonagenarios ingresados en un hospital general: epidemiología, clínica y factores pronósticos

Background. Seasonal influenza is responsible for high annual morbidity and mortality worldwide, especially in elderly patients. The aim of the study was to analyse the epidemiological, clinical and prognostic features of influenza in octogenarians and nonagenarians admitted to a general hospital, as well as risk factors associated with mortality. Methods. Retrospective, cross-sectional, descriptive study in patients admitted and diagnosed with influenza by molecular biology in the General University Hospital of Alicante from 1 January to 31 April 2015. Results. A total of 219 patients were diagnosed with influenza in the study period: 55 (25.1%) were ≤64 years-old; 77 (35.2%) were aged 65-79; 67 (30.6%) were aged 80-89 years; and 20 (9.1%) were aged ≥90 years. Most flu episodes were caused by influenza A (n=181, 82.6%). Patients aged 80 years or older had lower glomerular filtration rate (mean: 49.7 mL/min vs. 62.2 mL/min; p=0.006), a greater need for non-invasive mechanical ventilation (22% vs 9.3%; p=0.02), greater co-morbidity due to cardiac insufficiency (40.5% vs. 16.4%; p<0.001) and chronic renal disease (32.9 vs. 20%, p=0.03), and greater mortality (19% vs. 2.9%; p<0.001). In a multivariate analysis, mortality was higher in those aged 80 or over (adjusted odds ratio [ORa] 9.2, 95% confidence interval [CI] 1.65-51.1), those who had acquired the flu in a longterm care facility (ORa 11.9, 95% CI 1.06-134), and those with hyperlactataemia (ORa 1.89, 95% CI 1.20-3.00). Conclusions. Seasonal influenza is a serious problem leading to elevated mortality in octogenarian and nonagenarian patients admitted to a general hospital (AU)

Introducción. La gripe epidémica estacional es responsable de una elevada morbi-mortalidad cada año en el mundo especialmente en pacientes de edad avanzada. El objetivo del estudio fue presentar las características epidemiológicas, clínicas y pronósticas de la gripe estacional en octogenarios y nonagenarios ingresados en un hospital general y analizar los factores asociados con la mortalidad. Material y métodos. Estudio descriptivo transversal retrospectivo de los pacientes ingresados con gripe diagnosticados por biología molecular en el Hospital General Universitario de Alicante desde el 1 de enero del 2015 hasta 31 de abril del 2015. Resultados. En el periodo de estudio fueron diagnosticados 219 pacientes, de ellos 55 (25,1%) eran ≤64 años, 77 (35,2%) adultos de entre 65 y 79 años, 67 (30,6%) entre 80-89 años y 20 (9,1%) ≥90 años. La mayoría de los episodios fueron gripe causada por influenza A (n=181; 82,6%). Los pacientes ≥ 80 años tenían unos valores medios de un filtrado glomerular inferior (media: 49,7 mL/ min vs. 62.2 mL/min; p=0,006), mayor requerimiento de ventilación mecánica no invasiva (22% vs 9,3%; p=0,02), una mayor comorbilidad por insuficiencia cardiaca (40,5% vs. 16,4%p<0,001) y enfermedad renal crónica (32,9 vs. 20%, p=0,03), así como mayor mortalidad (19% vs. 2,9%; p<0,001). En el análisis multivariado, la mortalidad fue superior en los mayores de 80 años (odds ratio ajustada [ORa]: 9,2, intervalo de confianza [IC] del 95%: 1,65-51,1), con adquisición de la gripe en un centro socio sanitarios (ORa: 11,9, IC 95%: 1,06-134) y la hiperlactacidemia (ORa: 1,89, IC 95%: 1,20-3,00). Conclusiones. La gripe es un grave problema con elevada mortalidad en pacientes octogenarios y nonagenarios ingresados en un hospital general (AU)