[Clinical characteristics and risk factors for mortality upon admission in patients with heart failure hospitalized due to COVID-19 in Spain]. / Características clínicas y factores de riesgo de mortalidad al ingreso en pacientes con insuficiencia cardíaca hospitalizados por COVID-19 en España.

Background: There are few studies on patients with heart failure (HF) hospitalized for COVID-19. Our aim is to describe the clinical characteristics of patients with HF hospitalized for COVID-19 and identify risk factors for in-hospital mortality upon admission. Methods: We conducted a retrospective, multicenter study in patients with HF hospitalized for COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry). A multivariate logistic regression analysis was performed to identify admission risk factors associated with in-hospital mortality. Results: A total of 1,718 patients were analyzed (56.5% men; median age 81.4 years). The overall case fatality rate was 47.6% (n=819). The independent risk factors at admission for in-hospital mortality were: age (adjusted odds ratio [AOR]: 1.03; 95% confidence interval [95%CI]: 1.02-1.05; p< .001); severe dependence (AOR: 1.62; 95%CI: 1.19-2.20; p=.002); tachycardia (AOR: 1.01; 95%CI: 1.00-1.01; p=.004); and high C-reactive protein (AOR: 1.004; 95%CI:1.002-1.004; p< .001), LDH (AOR: 1.001; 95%CI: 1.001-1.002; p< .001), and serum creatinine levels (AOR: 1.35; 95%CI: 1.18-1.54; p< .001). Conclusions: Patients with HF hospitalized for COVID-19 have a high in-hospital mortality rate. Some simple clinical and laboratory tests can help to identify patients with a worse prognosis.

Recommendations on the comprehensive, multidimensional assessment of hospitalized elderly people. Position of the Spanish Society of Internal Medicine. / Recomendaciones sobre la valoración integral y multidimensional del anciano hospitalizado. Posicionamiento de la Sociedad Española de Medicina Interna.

This position paper describes the most relevant and essential aspects of a comprehensive, multidimensional assessment of hospitalized elderly people. The change in demographic patterns and the epidemiological profiles of diseases makes it necessary for internal medicine departments to adapt in order to take into account the vulnerabilities of the elderly in this context. A comprehensive, multidimensional assessment and the multidisciplinary development of a care plan during hospitalization can have an impact in terms of preventing mortality, disability, and institutionalization at discharge. It is necessary for all internists to acquire skills to improve the hospitalization experience in the elderly and obtain better health outcomes in our patients. This document has been developed by the Focus Group on Aging and the Polypathological and Advanced Age Working Group and endorsed by the Spanish Society of Internal Medicine.

Assessment of long-term cognitive dysfunction in older patients who undergo heart surgery.

INTRODUCTION: Older patients are more likely to have cognitive dysfunction, and a great proportion of patients undergone surgical procedures are older adults. Postoperative cognitive dysfunction (POCD) has been shown as a consistent complication after major surgical procedures such as heart surgery. AIM: To determine the presence of long-term POCD in ≥65-year-old patients undergoing coronary artery bypass grafting and aortic valve replacement, and to establish related risk factors. METHODS: We prospectively and sequentially included 44 patients with coronary disease and aortic stenosis scheduled for heart surgery. Follow-up of all patients was standardized and a neurocognitive evaluation were performed preoperatively and at 1, 6 and 12 months after surgery. RESULTS: Patients experienced a significantly postoperative cognitive dysfunction (33.5%, 63.4% and 38.9% at 1, 6 and 12 months, respectively) from baseline (20.5%). Patient-associated aspects such as age (p<0.01), history of smoking (p<0.01), arterial hypertension (p=0.022), diabetes mellitus (p=0.024), heart failure (p=0.036) and preoperative cognitive dysfunction (p<0.01), and surgery-associated aspects such as EuroSCORE (p<0.01) and operation time (p<0.01) were identified as related risk factors. CONCLUSIONS: Older patients who underwent heart surgery had long-term POCD. Both patient- and surgery-related risk factors were established as related risk factors. These findings suggest that the prevalence of cognitive dysfunction after cardiac surgery in older patients could be related to a possible progression to dementia. In addition, many of the risk factors identified may be modifiable but in practice, these patients are not attended to for their possible cognitive impairment.

Clinical characteristics and risk factors for mortality upon admission in patients with heart failure hospitalized due to COVID-19 in Spain.

BACKGROUND: There are few studies on patients with heart failure (HF) hospitalized for COVID-19. Our aim is to describe the clinical characteristics of patients with HF hospitalized for COVID-19 and identify risk factors for in-hospital mortality upon admission. METHODS: We conducted a retrospective, multicenter study in patients with HF hospitalized for COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry). A multivariate logistic regression analysis was performed to identify admission factors associated with in-hospital mortality. RESULTS: A total of 1718 patients were analyzed (56.5% men; median age 81.4 years). The overall case fatality rate was 47.6% (n = 819). The independent risk factors at admission for in-hospital mortality were: age (adjusted odds ratio [AOR]: 1.03; 95% confidence interval [95%CI]: 1.02-1.05; p < 0.001); severe dependence (AOR: 1.62; 95%CI: 1.19-2.20; p = 0.002); tachycardia (AOR: 1.01; 95%CI: 1.00-1.01; p = 0.004); and high C-reactive protein (AOR: 1.004; 95%CI:1.002-1.004; p < 0.001), LDH (AOR: 1.001; 95%CI: 1.001-1.002; p < 0.001), and serum creatinine levels (AOR: 1.35; 95%CI: 1.18-1.54; p < 0.001). CONCLUSIONS: Patients with HF hospitalized for COVID-19 have a high in-hospital mortality rate. Some simple clinical and laboratory tests can help to identify patients with a worse prognosis.

Recommendations on the comprehensive, multidimensional assessment of hospitalized elderly people. Position of the Spanish Society of Internal Medicine.

This position paper describes the most relevant and essential aspects of a comprehensive, multidimensional assessment of hospitalized elderly people. The change in demographic patterns and the epidemiological profiles of diseases makes it necessary for internal medicine departments to adapt in order to take into account the vulnerabilities of the elderly in this context. A comprehensive, multidimensional assessment and the multidisciplinary development of a care plan during hospitalization can have an impact in terms of preventing mortality, disability, and institutionalization at discharge. It is necessary for all internists to acquire skills to improve the hospitalization experience in the elderly and obtain better health outcomes in our patients. This document has been developed by the Focus Group on Aging and the Polypathological and Advanced Age Working Group and endorsed by the Spanish Society of Internal Medicine.

Assessment of long-term cognitive dysfunction in older patients who undergo heart surgery.

INTRODUCTION: Older patients are more likely to have cognitive dysfunction, and a great proportion of patients undergone surgical procedures are older adults. Postoperative cognitive dysfunction (POCD) has been shown as a consistent complication after major surgical procedures such as heart surgery. AIM: To determine the presence of long-term POCD in ≥65-year-old patients undergoing coronary artery bypass grafting and aortic valve replacement, and to establish related risk factors. METHODS: We prospectively and sequentially included 44 patients with coronary disease and aortic stenosis scheduled for heart surgery. Follow-up of all patients was standardized and a neurocognitive evaluation were performed preoperatively and at 1, 6 and 12 months after surgery. RESULTS: Patients experienced a significantly postoperative cognitive dysfunction (33.5%, 63.4% and 38.9% at 1, 6 and 12 months, respectively) from baseline (20.5%). Patient-associated aspects such as age (p<0.01), history of smoking (p<0.01), arterial hypertension (p=0.022), diabetes mellitus (p=0.024), heart failure (p=0.036) and preoperative cognitive dysfunction (p<0.01), and surgery-associated aspects such as EuroSCORE (p<0.01) and operation time (p<0.01) were identified as related risk factors. CONCLUSIONS: Older patients who underwent heart surgery had long-term POCD. Both patient- and surgery-related risk factors were established as related risk factors. These findings suggest that the prevalence of cognitive dysfunction after cardiac surgery in older patients could be related to a possible progression to dementia. In addition, many of the risk factors identified may be modifiable but in practice, these patients are not attended to for their possible cognitive impairment.

Efficacy and safety of replacing sitagliptin with canagliflozin in real-world patients with type 2 diabetes uncontrolled with sitagliptin combined with metformin and/or gliclazide: The SITA-CANA Switch Study.

AIM: To analyze the efficacy and safety of replacing sitagliptin with canagliflozin in patients with type 2 diabetes (T2D) and poor metabolic control despite treatment with sitagliptin in combination with metformin and/or gliclazide. MATERIALS AND METHODS: In this multicentre observational, retrospective, 26-week clinical study of patients with T2D and poor glycaemic control (HbA1c: 7.5-9.5%) treated with sitagliptin in combination with metformin and/or gliclazide, sitagliptin (and gliclazide if appropriate) were replaced by canagliflozin. The main outcome of the study was the proportion of patients who achieved good glycaemic control (HbA1c<7%) by the end of the study. RESULTS: The study sample comprised 50 patients (baseline HbA1c 8.0±0.6%) treated with sitagliptin 100mg/day, 14 of whom were also taking gliclazide 60mg/day while 38 were taking metformin 1700mg/day. Sitagliptin treatment was replaced by either canagliflozin 100mg (n=17) or 300mg (n=33). After 26 weeks of follow-up, these patients presented with significant decreases in HbA1c (-1.1%; P<0.000), weight (-3.89kg; P<0.000), BMI (-1.37kg/m2; P<0.022), abdominal circumference (-5.42cm; P<0.004), systolic and diastolic blood pressure (-5.3mmHg and -4.4mmHg, respectively; P=0.005), triglycerides (-42mg/dL; P=0.005) and LDL/HDL cholesterol ratio (-0.34; P=0.005). By the end of the study, 42% of patients had achieved HbA1c levels<7%. CONCLUSION: In patients with T2D poorly controlled with sitagliptin, whether alone or in combination with metformin and/or gliclazide, replacing it with canagliflozin may be a simple yet effective intensification strategy. Our results, which may have important implications for clinical practice, now need to be confirmed in larger observational studies.

Delayed gastric emptying and altered antrum protein metabolism during activity-based anorexia.

BACKGROUND: Anorexia nervosa, a restrictive eating disorder, is often associated with gastrointestinal disorders, particularly a delayed gastric emptying. However, the mechanisms remained poorly documented. Thus, we aimed to evaluate gastric emptying and antrum protein metabolism in the Activity-Based Anorexia model (ABA). METHODS: Females C57Bl/6 mice were randomized into 3 groups: Control, ABA, and Limited Food Access (LFA). Food access has been progressively limited from 6 h/day at day 6 to 3 h/day at day 9 and until day 17. ABA mice had free access to an activity wheel. Gastric emptying was assessed. On gastric extracts, a proteomic analysis was performed, as well as an evaluation of protein synthesis and protein oxidation. KEY RESULTS: Both LFA and ABA mice exhibited a delayed gastric emptying compared with Controls (P < .05). Proteomic approach revealed 15 proteins that were differentially expressed. Among these proteins, we identified 2 clusters of interest contributing to (i) the organization of muscle fiber with ACTA2, VCL, KRT19, KRT8, and DES proteins and (ii) "heat shock proteins" with STIP1, HSPD1, and HSPA8 proteins. ABA mice specifically exhibited an increased rate of gastric oxidized proteins. CONCLUSIONS AND INFERENCES: Delayed gastric emptying observed in anorectic conditions appears to be secondary to malnutrition. However, an oxidative stress is specifically present in the stomach of ABA mice. Its role remains to be further studied.

Concordance of Barthel Index, ECOG-PS, and Palliative Performance Scale in the assessment of functional status in patients with advanced medical diseases.

OBJECTIVE: Analysing most relevant clinical features and concordance between different functional scales in patients with advanced medical diseases (PAMD). METHODS: Cross-sectional multicentre study that included PAMD (heart, lung, kidney, liver, and neurological diseases) in hospital settings from February 2009 to October 2010. We analysed clinical, biological and functional features in performing activities of daily living (ADL) by medians of Barthel Index (BI); additionally we assessed their performance status by medians of Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) and Palliative Performance Scale (PPS) scores. We evaluated the concordance of these instruments in assessing functional impairment by κ and intraclass correlation coefficient tests. RESULTS: 1847 patients were included (average age 79 years, 50.1% men). Most common symptoms were dyspnoea (62.31%), asthenia (23%) and delirium (20.14%). Functional assessment showed a high prevalence of severe or total impairment in performing basic ADL by medians of used instruments (BI median=35 (IQR=70), and 52.1% of patients with severe-total impairment; ECOG-PS median=2 (IQR 30), and 44% of patients with severe-total impairment; and PPS median=50 (IQR 30), and 32% of patients with severe-total impairment). Concordance among these instruments was acceptably good (κ indexes ranging from 0.653 to 0.745 (p<0.0001)). CONCLUSIONS: PAMD represent a population with severe functional impairment, which requires a multidisciplinary approach for proper management. Assessment of functional ability in this population by BI, ECOG-PS, and PPS showed good concordance.

Reservoirs of HIV replication after successful combined antiretroviral treatment.

Sustained reduction of viral replication can be achieved in HIV infected patients after treatment with combinations of drugs (HAART) that inhibit the viral reverse transcriptase, and protease enzymes. However, replication competent virus can still be recovered from latently infected resting memory CD4+ T-cell lymphocytes. Moreover, "covert" virus replication has been demonstrated in patients who experienced reductions in plasma viremia to levels below the limit of detection of the most sensitive PCR assays. In most studies, preferential attention has been given to latent resting CD4+ T-lymphocytes as a source of HIV persistence. However, insufficient suppression of HIV replication could also lead to viral re-emergence after HAART interruption. In addition to CD4+ T- lymphocytes, other host cells such as long-lived resident macrophages or recently infected blood monocytes could also contribute to maintain persistent HIV replication after HAART. Establishing the origin of re-emerging HIV in patients under HAART upon treatment interruption is important to design optimal treatment schemes. Therapeutic strategies aimed at reducing the number of latently infected cells involve immune activation with IL-2, or other stimulatory factors, in the presence of antiretroviral drugs. Elimination of replication-competent virus would require intensification of HAART, or the use of antiretroviral drugs achieving an effective concentration at the site of HIV replication. In this review the mechanisms of HIV persistence and the methods that can be used to distinguish latent from covert HIV replication in different cell types will be discussed.

[Human immunodeficiency virus (HIV) co-receptors expression in mononuclear leucocytes (ML) of HIV+ patients]. / Expresion de co-receptores para el virus de la inmunodeficiencia humana (VIH) luego del cultivo de leucocitos mononucleares (LM) de pacientes VIH+.

Variations of the expression of CXCR4 and CCR5 HIV co-receptors after non stimulated culture of peripheral blood mononuclear cells (PBMC) from HIV+ patients were studied. Expression of CCR5 on both CD4+ and CD8+ T lymphocytes was reduced after 7 days and remained low throughout the culture. CXCR4 levels remained stable in both lymphocyte subpopulations. No significant changes were observed in control HIV- PBMC cultures. In order to ascertain if the CCR5 changes were associated to in vitro HIV replication, 6 days pre-cultured HIV- PBMC were infected with HIV+ culture supernatants. After 3 days CCR5 expression was reduced both in CD4+ and in CD8+ T lymphocytes, while CXCR4 expression was not, coincident with initiation of HIV replication in culture. These results suggest that CCR5 down modulation in CD4+ or CD8+ T lymphocytes is a consequence of HIV replication.

[Apoptosis and human immunodeficiency virus infection (HIV]. / Apoptosis e infección por el virus de la inmunodeficiencia humana (HIV).

Generalized activation of the immune system after HIV infection leads to an exacerbation of all apoptotic mechanisms. CD4+, CD8+ T lymphocytes and B lymphocytes are sensitized to apoptotic stimuli. Macrophages are important in the removal of apoptotic cells, they prevent apoptotic cell accumulation during in vitro culture and they may lead to enhanced CD4+ T lymphocyte cell death through indirect mechanisms. A simple procedure for prolonged culture of peripheral blood mononuclear cells from HIV+ patients is discussed, in relation to its convenience to evaluate apoptosis, cell to cell interaction and HIV replication in the absence of exogenously added stimuli or co-culture of allogeneic cells. In this system, HIV replication takes place primarily in cells of macrophage lineage that may be activated into differentiation through removal of apoptotic debris during the culture.

[HIV infected macrophages isolated from HIV+ patients with undetectable viral load undergoing combined antiretroviral treatment]. / Macrófagos infectados por HIV aislados de pacientes HIV+ con carga viral indetectable luego del tratamiento antirretroviral combinado.

A new method of culture of peripheral blood leukocytes (PBMC) from HIV+ patients, in the absence of exogenous stimuli (allogeneic cells or cytokines) (PBMC w/s) was used for the detection of persistent viral infection in HIV patients who had undergone successful highly active antiretroviral therapy (HAART) lowering their viral burden to undetectable levels (< 50 RNA copies/ml). Infected cells were always of the monocyte/macrophage lineage (M). No infection could be detected in these patients using the classical system (co-culture with HIV-CMP activated with PHA and IL-2). Differences in the class of target cells (higher proportion of proliferating M and CCR5 expressing cells in the PBMC w/s system than in PBMC-PHA cultures) may determine the relative sensitivity of each technique to achieve successful isolation of HIV from different patients.

Factors involved in the generation of memory CD8+ T cells in patients with X-linked lymphoproliferative disease (XLP).

UNLABELLED: We have analysed the phenotype of T lymphocytes in two X-linked lymphoproliferative disease (XLP) patients with the same SH2D1A mutation differing in initial exposure to Epstein-Barr virus (EBV) and treatment. While memory T lymphocytes (with low CCR7 and CD62L expression) prevailed in both XLP patients, in patient 9, who developed acute infectious mononucleosis (AIM) and received B cell ablative treatment, the predominant phenotype was that of late effector CD8 T cells (CD27-, CD28-, CCR7-, CD62L-, CD45 RA+, perforin+), while in patient 4 (who did not suffer AIM) the prevalent phenotype of CD8 T lymphocytes was similar to that of normal controls (N) or to that of adult individuals who recovered from AIM: CD27+ , CD28+, CCR7-, CD62L-, CD45 RO+ and perforin-. CD57 expression (related to senescence) was also higher in CD8 T cells from patient 9 than in patient 4, AIM or N. Persistently high EBV viral load was observed in patient 9. The results obtained from this limited number of XLP patients suggest that events related to the initial EBV encounter (antigen load, treatment, cytokine environment) may have more weight than lack of SH2D1A in determining the long-term differentiation pattern of CD8 memory T cells.

Immortalized Epstein-Barr virus-positive B-cell lines obtained by prolonged culture of peripheral blood mononuclear cells from human immunodeficiency virus type 1-positive patients.

OBJECTIVES: To study the factors that determine malignant B cell growth in human immunodeficiency virus type 1 (HIV-1)-infected patients. STUDY DESIGN: B-cell lines (lymphocyte cell lines [LCL]) were developed after nonstimulated culture of peripheral blood mononuclear cells (PBMC) from HIV-1-positive (HIV-1(+)) patients. Human immunodeficiency virus type 1 replication in culture, Epstein-Barr virus (EBV) latent oncogene expression, and cell-to-cell interaction were studied after nonstimulated culture of HIV-1(+) PBMC, analyzing their contribution to LCL appearance. METHODS: Nonstimulated PBMC cultures of HIV-1(+) PBMC and controls (N-PBMC) were established. Lymphocyte cell lines were characterized. Epstein-Barr virus latent membrane protein 1 (LMP-1) and Epstein-Barr nuclear antigen 2 were detected by polymerase chain reaction (PCR). Clonality of LCL was determined by light chain restriction (flow cytometry) and immunoglobulin H chain rearrangement (semi-nested PCR). Peripheral blood mononuclear cell phenotypes were studied at different intervals of culture. RESULTS: Lymphocyte cell lines were obtained in 73% of HIV-1(+) PBMC cultures, compared with 6% in N-PBMC. All LCL were EBV-positive (EBV(+)). B-cell lineage was established, and up to 12 different B-cell clones were expanded from the same individual. Occurrence of LCL was more frequent in cultures with HIV-1 replication, high LMP-1 expression in viable B cells, and high CD4:CD8 ratio. Human immunodeficiency virus type 1 replication persisted in 53% of the LCL. CONCLUSIONS: In vitro HIV-1 replication and persistence of viable EBV(+) lymphoblasts favor spontaneous in vitro outgrowth of LCL in HIV-1(+) patients.

HCV recovery from peripheral blood mononuclear cell culture supernatants derived from HCV-HIV co-infected haemophilic patients with undetectable HCV viraemia.

Hepatitis C viraemia, in 38 human immunodeficiency virus positive (HIV+)/hepatitis C virus positive (HCV+) patients, was determined in haemophilic patients during the 4 years since initiation of highly active antiretroviral therapy (HAART). Six of 38 patients had persistently HCV-negative viraemia for more than 2 years. No correlation between HCV-negative viraemia and CD4+ T-cell counts, HIV viral load, age, type or severity of haemophilia could be established. Reduced levels of HIV viral load and the immune reconstitution that follows the initiation of HAART were not enough to explain the disappearance of HCV from plasma. Individuals who cleared plasma HCV had significantly higher CD8+ T-cell counts (P=0.0013) (mean +/- SE: 1153 +/- 117.8 cells microL(-1)) than those with HCV-positive viraemia (819.1 +/- 40.72 cells microL(-1)). Because HCV could maintain a low replication level in peripheral blood mononuclear cells (PBMC), we cultured PBMC of five of six patients with undetectable HCV viraemia. We found four of five HCV RNA-positive cultures. The presence of HCV RNA in our cultures proved that these cells may be an important viral reservoir that could contribute to HCV recurrence in plasma even after long periods of negative viraemia. In summary, our results indicate that in spite of prolonged HCV-negative plasma viraemia, HCV patients that are co-infected with HIV may harbour replication-competent HCV in their PBMC. Therefore, true clearance of HCV infection is difficult to achieve in these patients.