Impacto de la fragilidad en la supervivencia intrahospitalaria en pacientes mayores con infección por COVID-19: la importancia de su identificación temprana. Registro Nacional SEMI-COVID / The impact of frailty on intra-hospital survival in older patients with COVID-19 infection: The importance of early identification. SEMI-COVID National Registry

Introducción La evidencia reciente sugiere que la fragilidad puede ser un importante predictor de resultados adversos en personas mayores hospitalizadas por COVID-19. El objetivo de este estudio es determinar el valor pronóstico de la fragilidad en la supervivencia intrahospitalaria de estos pacientes. Métodos Estudio observacional, multicéntrico y de ámbito nacional de pacientes ≥70 años hospitalizados a consecuencia de la COVID-19 en España desde el 1 de marzo hasta el 31 de diciembre de 2020. Los datos de los pacientes se obtuvieron del Registro SEMI-COVID-19 de la Sociedad Española de Medicina Interna. Se utilizó la escala de fragilidad Clínica (CFS, por sus siglas en inglés) para evaluar la fragilidad. El resultado primario fue la supervivencia hospitalaria. Se realizó un modelo de riesgos proporcionales de Cox para evaluar los predictores de supervivencia. Resultados Se incluyeron 1.878 participantes (52% varones y 48% mujeres). Mil trescientos cincuenta y un supervivientes (71,9%) y 527 no supervivientes (28,1%). El grupo de no supervivientes presentaba en comparación con los supervivientes una media de edad superior (83,5 frente a 81 años), más comorbilidades (6,3 frente a 5,3 puntos en el índice de Charlson), mayor grado de dependencia (26,8 frente al 12,4% de pacientes con dependencia severa) y de fragilidad (34,5 frente al 14,7% de pacientes con fragilidad severa), sin embargo, no hubo diferencias en cuanto al sexo. Nuestros resultados muestran que un grado de fragilidad moderado-grave es el principal factor asociado de forma independiente con una menor supervivencia (HR: 2,344; 1,437-3,823; p<0,001 para SFC 5-6 y HR: 3,694; 2,155-6,330; p<0,001 para SFC 7-9. Conclusiones La fragilidad es el principal predictor de resultados adversos en pacientes mayores con COVID-19. El uso de herramientas como la CFS es fundamental para la detección precoz de fragilidad en esta población (AU)

Background Emerging evidence suggests that frailty may be a significant predictor of poor outcomes in older individuals hospitalized due to COVID-19. This study aims to determine the prognostic value of frailty on intrahospital patient survival. Methods This observational, multicenter, nationwide study included patients aged 70 years and older who were hospitalized due to COVID-19 in Spain between March 1 and December 31, 2020. Patient data were obtained from the SEMI-COVID-19 Registry of the Spanish Society of Internal Medicine. Frailty was assessed using the Clinical Frailty Scale. The primary outcome was hospital survival. Cox proportional hazards models were used to assess predictors of survival. Results A total of 1878 participants (52% men and 48% women) were included, with 1351 (71.9%) survivors and 527 (28.1%) non-survivors. The non-survivor group had higher mean age (83.5 vs. 81 years), comorbidities (6.3 vs. 5.3 points on the Charlson index), degree of dependency (26.8% vs. 12.4% severely dependent patients), and frailty (34.5% vs. 14.7% severely frail patients) compared to survivors. However, there were no differences in terms of sex. Our results demonstrate that a moderate–severe degree of frailty is the primary factor independently associated with shorter survival (HR 2.344; 1.437-3.823; p < 0.001 for CFS 5-6 and 3.694; 2.155–6.330; p < 0.001 for CFS 7-9). Conclusion Frailty is the main predictor of adverse outcomes in older patients with COVID-19. The utilization of tools such as the Clinical Frailty Scale is crucial for early detection in this population (AU)

Características de los pacientes hospitalizados con hipercalcemia en la provincia de Málaga: estudio longitudinal, retrospectivo y multicéntrico / Characteristics of hospitalized patients with hypercalcemia in the province of Malaga: A longitudinal, retrospective, multicenter study

Antecedentes y objetivo Existen escasos estudios que analicen la hipercalcemia en pacientes hospitalizados. Nuestros objetivos fueron: describir las características clínicas de los pacientes hospitalizados con hipercalcemia, estimar su prevalencia en el medio hospitalario, analizar la tasa de corrección de la hipercalcemia, e identificar variables pronósticas. Materiales y métodos Estudio observacional, longitudinal, retrospectivo y bicéntrico. Se incluyeron pacientes adultos ingresados en dos hospitales de Málaga (2014-2018) con diagnóstico de hipercalcemia. El seguimiento mínimo fue de 2años o hasta el fallecimiento. Resultados Se incluyeron 205 pacientes con hipercalcemia (incidencia: 0,13%). La edad media (DE) fue de 68,2 (13,1) años, con predominio de varones (55,1%). La calcemia mediana (RIC) al ingreso fue de 13,1 (11,8-14,6) mg/dL. Las etiologías más frecuentes fueron: neoplasias (75,1%), hiperparatiroidismo primario y fármacos (ambas, 8,8%). La mediana (RIC) de seguimiento fue de 5,1 (1,7-60,3) semanas. Los tratamientos más usados fueron: fluidoterapia (86,8%), diuréticos de asa (70,9%), bifosfonatos (60,7%) y glucocorticoides (46,2%). La tasa de corrección de la hipercalcemia fue del 65,2%, con una mediana (RIC) de 6 (3-10) días La tasa de mortalidad fue del 81,5%. La mediana (IC95%) de supervivencia fue de 5,1 (3-7,3) semanas. Los factores asociados a una mayor mortalidad fueron: edad avanzada, etiología neoplásica, calcemia al ingreso y no corrección de la hipercalcemia. Conclusiones La hipercalcemia en pacientes hospitalizados se debe principalmente a procesos neoplásicos y se asocia a una elevada mortalidad. Observamos una baja tasa de seguimiento de las recomendaciones para el manejo de la hipercalcemia (AU)

Background and objective There are limited studies analyzing hypercalcemia in hospitalized patients. Our objectives were to describe the clinical characteristics of hospitalized patients with hypercalcemia, estimate its prevalence in the hospital setting, analyze the rate of correction of hypercalcemia, and identify prognostic variables. Materials and methods Observational, longitudinal, retrospective, and bicentric study. Adult patients admitted to two hospitals in Málaga (2014-2018) with a diagnosis of hypercalcemia were included. The minimum follow-up was 2years or until death. Results A total of 205 patients with hypercalcemia were included (incidence: 0.13%). The mean age (SD) was 68.2 (13.1) years, with a predominance of males (55.1%). The median (IQR) serum calcium at admission was 13.1 (11.8-14.6) mg/dL. The most common etiologies were neoplasms (75.1%), primary hyperparathyroidism, and medications (both 8.8%). The median (IQR) follow-up period was 5.1 (1.7-60.3) weeks. The most commonly used treatments were fluid therapy (86.8%), loop diuretics (70.9%), bisphosphonates (60.7%), and glucocorticoids (46.2%). The rate of correction of hypercalcemia was 65.2%, with a median (IQR) of 6 (3-10) days. The mortality rate was 81.5%. The median (95%CI) survival was 5.1 (3-7.3) weeks. Factors associated with higher mortality were advanced age, neoplastic etiology, serum calcium at admission, and failure to correct hypercalcemia. Conclusions Hypercalcemia in hospitalized patients is mainly due to neoplastic processes and is associated with high mortality. We observed a low rate of adherence to recommendations for the management of hypercalcemia (AU)

Characteristics of hospitalized patients with hypercalcemia in the province of Malaga: a longitudinal, retrospective, multicenter study.

BACKGROUND AND OBJECTIVE: There are limited studies analyzing hypercalcemia in hospitalized patients. Our objectives were to describe the clinical characteristics of hospitalized patients with hypercalcemia, estimate its prevalence in the hospital setting, analyze the rate of correction of hypercalcemia, and identify prognostic variables. MATERIALS AND METHODS: Observational, longitudinal, retrospective, and bicentric study. Adult patients admitted to two hospitals in Málaga (2014-2018) with a diagnosis of hypercalcemia were included. The minimum follow-up was 2 years or until death. RESULTS: A total of 205 patients with hypercalcemia were included (incidence: 0.13%). The mean age (SD) was 68.2 (13.1) years, with a predominance of males (55.1%). The median (IQR) serum calcium at admission was 13.1 (11.8-14.6) mg/dl. The most common etiologies were neoplasms (75.1%), primary hyperparathyroidism, and medications (both 8.8%). The median (IQR) follow-up period was 5.1 (1.7-60.3) weeks. The most commonly used treatments were fluid therapy (86.8%), loop diuretics (70.9%), bisphosphonates (60.7%), and glucocorticoids (46.2%). The rate of correction of hypercalcemia was 65.2%, with a median (IQR) of 6 (3-10) days. The mortality rate was 81.5%. The median (95% CI) survival was 5.1 (3-7.3) weeks. Factors associated with higher mortality were advanced age, neoplastic etiology, serum calcium at admission, and failure to correct hypercalcemia. CONCLUSIONS: Hypercalcemia in hospitalized patients is mainly due to neoplastic processes and is associated with high mortality. We observed a low rate of adherence to recommendations for the management of hypercalcemia.

The impact of frailty on intra-hospital survival in older patients with COVID-19 infection: the importance of early identification. SEMI-COVID National Registry.

BACKGROUND: Emerging evidence suggests that frailty may be a significant predictor of poor outcomes in older individuals hospitalized due to COVID-19. This study aims to determine the prognostic value of frailty on intrahospital patient survival. METHODS: This observational, multicenter, nationwide study included patients aged 70 years and older who were hospitalized due to COVID-19 in Spain between March 1 and December 31, 2020. Patient data were obtained from the SEMI-COVID-19 Registry of the Spanish Society of Internal Medicine. Frailty was assessed using the Clinical Frailty Scale. The primary outcome was hospital survival. Cox proportional hazards models were used to assess predictors of survival. RESULTS: A total of 1,878 participants (52% men and 48% women) were included, with 1,351 (71.9%) survivors and 527 (28.1%) non-survivors. The non-survivor group had higher mean age (83.5 vs. 81 years), comorbidities (6.3 vs. 5.3 points on the Charlson index), degree of dependency (26.8% vs. 12.4% severely dependent patients), and frailty (34.5% vs. 14.7% severely frail patients) compared to survivors. However, there were no differences in terms of sex. Our results demonstrate that a moderate-severe degree of frailty is the primary factor independently associated with shorter survival [HR 2.344 (1.437-3.823; p<0.001) for CFS 5-6 and 3.694 (2.155-6.330; p<0.001) for CFS 7-9]. CONCLUSION: Frailty is the main predictor of adverse outcomes in older patients with COVID-19. The utilization of tools such as the Clinical Frailty Scale is crucial for early detection in this population.

Síndrome de COVID-19 persistente. Una revisión narrativa / Persistent COVID-19 syndrome. A narrative review

A medida que ha avanzado la pandemia de la enfermedad por coronavirus 2019 (COVID-19), originada por la infección por el coronavirus de tipo 2, causante del síndrome respiratorio agudo severo (SARS-CoV-2), el síndrome de COVID-19 persistente es un problema cada vez más reconocido y sobre el que se está desarrollando un importante volumen de publicaciones. Los síntomas pueden ser persistentes o aparecer, tras un periodo asintomático, semanas o meses después de la infección inicial. El cuadro clínico es tan marcadamente heterogéneo y multisistémico como en la fase aguda, por lo que se requiere un manejo multidisciplinar. Además, su aparición no está relacionada con la gravedad de la infección inicial, por lo que pueden afectar tanto a pacientes leves, incluso asintomáticos, como a enfermos graves que han requerido hospitalización. Aunque puede afectar a personas de cualquier edad, es más frecuente en mujeres de edad media. Las secuelas pueden generar un elevado impacto en la calidad de vida y en el ámbito laboral y social. El objetivo de este trabajo es hacer una revisión sobre el síndrome de COVID-19 persistente, conocer sus manifestaciones clínicas y las estrategias para el manejo y el seguimiento de estos pacientes (AU)

As the coronavirus-2019 disease (COVID-19) pandemic, caused by the infection with severe acute respiratory syndrome (SARS-CoV-2) coronavirus type 2, has progressed, persistent COVID-19 syndrome is an increasingly recognized problem on which a significant volume of medical literature is developing. Symptoms may be persistent or appear, after an asymptomatic period, weeks or months after the initial infection. The clinical picture is as markedly heterogeneous and multisystemic as in the acute phase, so multidisciplinary management is required. In addition, their appearance is not related to the severity of the initial infection, so they can affect both mild patients, even asymptomatic, and seriously ill patients who have required hospitalization. Although it can affect people of any age, it is more common in middle-aged women. The sequelae can generate a high impact on the quality of life, and in the work and social environment. The objective of this paper is to review persistent COVID-19 syndrome, to know its clinical manifestations and the strategies for the management and follow-up of these patients (AU)

Persistent COVID-19 syndrome. A narrative review.

As the coronavirus-2019 disease (COVID-19) pandemic, caused by the infection with severe acute respiratory syndrome (SARS-CoV-2) coronavirus type 2, has progressed, persistent COVID-19 syndrome is an increasingly recognized problem on which a significant volume of medical literature is developing. Symptoms may be persistent or appear, after an asymptomatic period, weeks or months after the initial infection. The clinical picture is as markedly heterogeneous and multisystemic as in the acute phase, so multidisciplinary management is required. In addition, their appearance is not related to the severity of the initial infection, so they can affect both mild patients, even asymptomatic, and seriously ill patients who have required hospitalization. Although it can affect people of any age, it is more common in middle-aged women. The sequelae can generate a high impact on the quality of life, and in the work and social environment. The objective of this paper is to review persistent COVID-19 syndrome, to know its clinical manifestations and the strategies for the management and follow-up of these patients.

[Persistent COVID-19 syndrome. A narrative review]. / Síndrome de COVID-19 persistente. Una revisión narrativa.

As the coronavirus-2019 disease (COVID-19) pandemic, caused by the infection with severe acute respiratory syndrome (SARS-CoV-2) coronavirus type 2, has progressed, persistent COVID-19 syndrome is an increasingly recognized problem on which a significant volume of medical literature is developing. Symptoms may be persistent or appear, after an asymptomatic period, weeks or months after the initial infection. The clinical picture is as markedly heterogeneous and multisystemic as in the acute phase, so multidisciplinary management is required. In addition, their appearance is not related to the severity of the initial infection, so they can affect both mild patients, even asymptomatic, and seriously ill patients who have required hospitalization. Although it can affect people of any age, it is more common in middle-aged women. The sequelae can generate a high impact on the quality of life, and in the work and social environment. The objective of this paper is to review persistent COVID-19 syndrome, to know its clinical manifestations and the strategies for the management and follow-up of these patients.

Chronic lymphocytic leukemia B cells inhibit spontaneous Ig production by autologous bone marrow cells: role of CD95-CD95L interaction.

A variable degree of humoral immunodeficiency is a common feature in patients with B-cell chronic lymphocytic leukemia (B-CLL). The aim of this study was to explore the possibility that B-CLL cells play a direct role in this phenomenon. To this end, patients' bone marrow (BM) immunoglobulin (Ig)-secreting cells were cocultured with autologous purified B-CLL cells. The results show that tumoral cells inhibited the spontaneous IgG secretion by BM plasma cells, and this effect increased after PMA-induction of B-CLL cells. This inhibitory process was proportional to the number of B-CLL cells added and depended on cellular contact. Adhesion molecules did not appear to be involved in the cellular interaction, because the inclusion of blocking antibody to a variety of these proteins did not reverse the inhibitory phenomenon. However, the addition of monoclonal antibody that blocked the function of either CD95 or CD95L clearly reversed B-CLL cell inhibition on autologous BM plasma cells. These latter cells were shown to express CD95, and B-CLL cells contained detectable quantities of CD95L at the level of messenger RNA and protein. Annexin V-binding experiments revealed increased apoptosis of BM Ig-secreting cells when cocultured with autologous B-CLL cells. Finally, this inhibitory phenomenon might be operative in vivo because (a) there was a good correlation between the intensity of the inhibitory effect in vitro and the serum IgG level exhibited by every patient and (b) B-CLL cells also inhibited in vivo antigen-induced IgG-tetanus toxoid-secreting cells obtained from normal immunized subjects. Collectively, these data suggest that B-CLL cells inhibit autologous CD95-bearing Ig-secreting cells by the interaction with CD95L present on B-CLL cells and, hence, contribute to the state of humoral immunodeficiency that occurs in these patients.

[Listeria monocytogenes infection in HIV patients: 2 new cases]. / Infección por Listeria monocytogenes en pacientes VIH: dos nuevos casos.

Two new cases of infection due to Listeria monocytogenes in two females with HIV are discussed, one of them with full blown AIDS and the other pregnant and without knowledge of her seropositivity until that moment. Its clinical manifestation as a meningeal manifestation and bacteremia, coincide with the few cases described until now; different hypothesis invoked until now are reviewed to justify this infrequent association HIV-Listeria.

CD5+ B lymphocytes in HIV infection: relationship to immunological progression of disease.

We analyzed CD5+ B cells in HIV-seropositive individuals because there is accumulating evidence of the involvement of this subset in natural immunity against virus and bacteria. There are also arguments maintaining that CD5+ B cells play a role in autoimmunity and lymphoid malignancies, both phenomena which are strongly associated with HIV infection. Seventy-two HIV-positive subjects (58 drug abusers, 7 homosexual men, 4 heterosexuals, and 3 hemophiliacs) were included in a phenotypic study of mononuclear cells. A direct immunofluorescence with doubly conjugated monoclonal antibodies was performed, and analysis was carried out in a FACScan cytometer. HIV-infected patients showed a striking increase in the percentage of CD5+ B lymphocytes (54.7 +/- 19% of circulating B cells) compared with HIV-negative drug users (35.5 + 14%) and with healthy controls (17 +/- 5%), P < 0.01 and P < 0.0001, respectively. In addition, levels of CD5+ B cells were correlated with CD4+ cell counts (r = -0.50373), WR staging (r = 0.5295), lymphocytopenia (r = 0.57356), and T4/T8 ratio (r = -0.3151) and showed a close association with the progression of immune system damage by HIV. Patients who developed hypergammaglobulinemia, thrombocytopenia, or other autoimmune manifestations associated with HIV infection showed levels of CD5+ B cells increased over those of the remaining HIV-seropositive individuals (P < 0.001, P < 0.001, and P < 0.05).

[Effect of cimetidine on free fatty acid liberation]. / Influencia de la cimetidina en la liberación de ácidos grasos libres.

Certain studies have brought to light the relationship between the administration of cimetidine and alterations of the lipidic metabolism. The changes in cholesterol levels observed after cimetidine administration have not yet been satisfactorily explained, at least in certain aspects. This paper studies free fatty acid behavior in a group of healthy volunteers who were given a 600 mg infusion of cimetidine. A significant drop (p less than 0.05) in fatty acids was found in these subjects in comparison with isolated physiological saline solution infusion. Our results imply that this fatty acid process may be involved in the lipid metabolism changes brought on by cimetidine administration.

Mononuclear cell subpopulations in human follicular fluid from stimulated cycles.

The study of lymphocyte subsets from human follicular fluid (FF) provides an opportunity to evaluate immunological features of the ovary. We investigated the mononuclear cell subsets in FF and peripheral blood obtained at the time of laparoscopy from ten in vitro fertilization (IVF) patients. Midcycle nonpregnant peripheral blood was used as the control. A marked increase in the proportion of monocytes (CD14+) was observed in FF. Although FF was enriched with CD8+ lymphocytes, a decrease in the proportion of CD4+ lymphocytes was observed. "Memory" T cells in FF, identified by the CD4+ CD45R- phenotype, predominated over "naive" T cells (CD4+ CD45R+) at a ratio of 2:1, which differs from the ratio yielded by control blood samples (1:1). The percentage of activated T cells (CD3+ HLA-DR+ cell) increased significantly in FF. When lymphocyte subsets were studied in the peripheral blood of IVF patients, changes similar to but less significant than those in FF were found. These data support the concept that lymphocytes play an important role in ovarian physiology.

[Changes in the activity of plasma renin and aldosterone induced by a pattern of increasing administration of zinc sulphate in normotensive individuals]. / Modificaciones en la actividad de renina plasmática y aldosterona provocadas por una pauta de administración creciente de sulfato de cinc en individuous normotensos.

The behavior of the renin-angiotensin-aldosterone system was evaluated in response to an increasing zinc intake. This oligoelement can modify the activity of the angiotensin I converting enzyme (ACE). Six healthy normotensive volunteers received 30 mg of zinc sulphate orally for 4 days and 600 mg for 4 additional days. On the first, fifth and ninth days plasma renin activity (PRA) and serum aldosterone were measured, and the possible changes in blood pressure were evaluated. PRA and aldosterone showed significant increases, with a stepwise distribution throughout the zinc overload. On the first day, PRA was 0.40 +/- 0.08 ng/ml/h; on the fifth day it was 0.80 +/- 0.21 ng/ml/h, and on the ninth day 1.39 +/- 0.34 ng/ml/h (1st-5th day; p less than 0.05; 1st-9th day: p less than 0.02). On the first day, the aldosterone levels were 81 +/- 17 pg/ml, on the fifth day they were 119 +/- 26 pg/ml, and on the ninth day 164 +/- 30 pg/ml (1st-5th day: nonsignificant difference; 1st-9th day: p less than 0.02). The values of arterial pressure did not change significantly after zinc overload. It is concluded that zinc overload can modify PRA and aldosterone levels, and that these changes are dose-related.