Treatment of COVID-19 pneumonia with low-dose radiotherapy plus standard of care versus standard of care alone in frail patients : The SEOR-GICOR IPACOVID comparative cohort trial.

PURPOSE: To assess the efficacy of lung low-dose radiotherapy (LD-RT) in the treatment of patients with COVID-19 pneumonia. MATERIALS AND METHODS: Ambispective study with two cohorts to compare treatment with standard of care (SoC) plus a single dose of 0.5 Gy to the whole thorax (experimental prospective cohort) with SoC alone (control retrospective cohort) for patients with COVID-19 pneumonia not candidates for admission to the intensive care unit (ICU) for mechanical ventilation. RESULTS: Fifty patients treated with LD-RT were compared with 50 matched controls. Mean age was 85 years in both groups. An increase in arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (PAFI) in the experimental LD-RT-treated group compared to the control group could not be found at 48 h after LD-RT, which was the primary endpoint of the study. However, PAFI values significantly improved after 1 month (473 vs. 302 mm Hg; p < 0.0001). Pulse oxymetric saturation/fraction of inspired oxygen (SAFI) values were also significantly higher in LD-RT-treated patients than in control patients at 1 week (405 vs. 334 mm Hg; p = 0.0157) and 1 month after LD-RT (462 vs. 326 mm Hg; p < 0.0001). All other timepoint measurements of the respiratory parameters were similar across groups. Patients in the experimental group were discharged from the hospital significantly earlier (23 vs. 31 days; p = 0.047). Fifteen and 26 patients died due to COVID-19 pneumonia in the experimental and control cohorts, respectively (30% vs. 48%; p = 0.1). LD-RT was associated with a decreased odds ratio (OR) for 1­month COVID-19 mortality (OR = 0.302 [0.106-0.859]; p = 0.025) when adjusted for potentially confounding factors. Overall survival was significantly prolonged in the LD-RT group compared to the control group (log-rank p = 0.027). No adverse events related to radiation treatment were observed. CONCLUSION: Treatment of frail patients with COVID-19 pneumonia with SoC plus single-dose LD-RT of 0.5 Gy improved respiratory parameters, reduced the period of hospitalization, decreased the rate of 1­month mortality, and prolonged actuarial overall survival compared to SoC alone.

Preliminary study on serum paraoxonase-1 status and chemokine (C-C motif) ligand 2 in hospitalized elderly patients with catheter-associated asymptomatic bacteriuria.

Urinary tract infections (UTI) are common among elderly patients in residential care facilities, as well as in the hospital setting. Identifying new biochemical markers of UTI is an active line of research since UTI management is resource intensive. Paraoxonase-1 (PON1) forms part of the patient's immune system, the response-to-injury and inflammation. Our study sought to evaluate alterations in inflammation-related paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2) in patients with an indwelling catheter to assess their potential usefulness as biomarkers of infection. Patients (n = 142) who had had the urinary catheter removed and 100 healthy volunteers were recruited. In all participants we measured serum PON1 activity, PON1 concentration, CCL2, procalcitonin and C-reactive protein (CRP). Results indicated that patients had higher CCL2, CRP and procalcitonin concentrations than the control group, and lower paraoxonase activity. There were no significant differences in PON1 concentrations. When comparing the diagnostic accuracy of CRP, procalcitonin, CCL2 and the PON1-related variables in discriminating between patients with and those without UTI, we found a considerable degree of overlap between groups, i.e., a low diagnostic accuracy. However, there were significant inverse logarithmic correlations between serum paraoxonase activity and the number of days the urinary catheter had been in situ. Our results suggest that measurement of these biochemical variables may be useful in investigating complications of long-term use of these devices and help to improve the economic and clinical investment required in the management of the often-associated infection.

[Differential pressure as an independent factor of cardiovascular risk]. / La presión diferencial como factor independiente de riesgo cardiovascular.

OBJECTIVES: To confirm that high differential pressure (DP) supposes greater risk of ischaemic cardiopathy and to assess whether it is also an independent risk factor of suffering a cerebrovascular accident. DESIGN: An analytical, observational, retrospective and longitudinal study with historic cohorts. SETTING: Urban population of about 18 000 inhabitants. PARTICIPANTS: 300 patients aged between 15 and 75 with hypertension of > or =2 years evolution, who have had their blood pressure taken by nurses 4 or more times (excluding casualty) and have not suffered a cardiovascular event (CVE), whether coronary accident, cerebrovascular accident or peripheral vasculopathy. MAIN MEASUREMENTS: The history relating to cardiovascular risk was recorded: lipaemia, obesity, tobacco dependency, diabetes mellitus, left ventricular hypertrophy (LVH). These factors were considered present if their diagnosis preceded the CVE diagnosis. They were placed in 2 groups, depending on the degree of differential pressure: "high" if >60 mm Hg and "not high" if (3/4)60 mm Hg. They were analysed for intention to treat over 10 years, with the appearance or not of a CVE as a response variable. RESULTS: 300 participants (73.3% women), 150 exposed to risk and 150 not exposed. The initial analysis showed significant differences between the 2 groups for age (P<.0001), diabetes (P<.0001), and LVH (P<.001). After logistic regression, the OR of suffering LVH was 2.38 (95% CI, 1.19-4.74) in the group with high DP; the OR of ischaemic cardiopathy, 2.84 (95% CI, 1.16-6.96); and of cerebrovascular accident, 2.70 (95% CI, 1.09-6.68). There were no significant differences for peripheral arteriopathy. CONCLUSIONS: DP was confirmed as an independent factor of cardiovascular risk and, despite the limitations of the study, it was pointed to as a possible independent factor of cerebrovascular risk.

La presión diferencial como factor independiente de riesgo cardiovascular / Differential pressure as an independent factor of cardiovascular risk

Objetivo. Confirmar que la presión diferencial alta supone más riesgo de cardiopatía isquémica y valorar si también es factor de riesgo independiente de padecer un accidente cerebrovascular. Diseño. Estudio longitudinal, analítico y observacional, retrospectivo de cohortes históricas. Emplazamiento. Población urbana de aproximadamente 18.000 habitantes. Participantes. Se incluyó en el estudio a 300 pacientes de 15 a 75 años de edad con hipertensión de 2 años de evolución o más, en los que constaban 4 o más determinaciones de presión arterial por enfermería (excluyendo urgencias) y que no habían padecido un episodio cardiovascular (ECV): coronariopatía, accidente cerebrovascular o vasculopatía periférica. Mediciones principales. Se registraron los antecedentes asociados a riesgo cardiovascular: dislipemia, obesidad, tabaquismo, diabetes mellitus e hipertrofia ventricular izquierda, y se consideraron presentes si su diagnóstico precedía al del ECV. Se realizó una clasificación en 2 grupos en función del grado de presión diferencial: alta si superaba los 60 mmHg (pacientes expuestos) y no alta si era >= 60 mmHg o inferior (pacientes no expuestos). Se realizó un análisis por intención de tratar durante 10 años señalando la aparición o no de ECV como variable de respuesta. Resultados. De los 300 participantes (un 73,3% mujeres), 150 se consideraron expuestos y 150 no expuestos. El análisis inicial mostró diferencias significativas entre ambos grupos respecto a la edad (p < 0,0001), presencia de diabetes (p < 0,0001) y de hipertrofia ventricular izquierda (p < 0,001). Tras la regresión logística, la odds ratio para padecer un ECV fue 2,38 (intervalo de confianza [IC] del 95%, 1,19-4,74) en el grupo de presión diferencial elevada. Para la cardiopatía isquémica la odds ratio fue de 2,84 (IC del 95%, 1,16-6,96) y para el accidente cerebrovascular, de 2,70 (IC del 95%, 1,09-6,68). Para arteriopatía periférica no hubo diferencias significativas. Conclusiones. Se confirma la presión diferencial como factor independiente de riesgo cardiovascular y se apunta, a pesar de las limitaciones del estudio, la posibilidad de que también sea un factor independiente de riesgo cerebrovascular

Objectives. To confirm that high differential pressure (DP) supposes greater risk of ischaemic cardiopathy and to assess whether it is also an independent risk factor of suffering a cerebrovascular accident. Design. An analytical, observational, retrospective and longitudinal study with historic cohorts. Setting. Urban population of about 18 000 inhabitants. Participants. 300 patients aged between 15 and 75 with hypertension of >=2 years evolution, who have had their blood pressure taken by nurses 4 or more times (excluding casualty) and have not suffered a cardiovascular event (CVE), whether coronary accident, cerebrovascular accident or peripheral vasculopathy. Main measurements. The history relating to cardiovascular risk was recorded: lipaemia, obesity, tobacco dependency, diabetes mellitus, left ventricular hypertrophy (LVH). These factors were considered present if their diagnosis preceded the CVE diagnosis. They were placed in 2 groups, depending on the degree of differential pressure: "high" if >60 mm Hg and "not high" if ¾60 mm Hg. They were analysed for intention to treat over 10 years, with the appearance or not of a CVE as a response variable. Results. 300 participants (73.3% women), 150 exposed to risk and 150 not exposed. The initial analysis showed significant differences between the 2 groups for age (P<.0001), diabetes (P<.0001), and LVH (P<.001). After logistic regression, the OR of suffering LVH was 2.38 (95% CI, 1.19-4.74) in the group with high DP; the OR of ischaemic cardiopathy, 2.84 (95% CI, 1.16-6.96); and of cerebrovascular accident, 2.70 (95% CI, 1.09-6.68). There were no significant differences for peripheral arteriopathy. Conclusions. DP was confirmed as an independent factor of cardiovascular risk and, despite the limitations of the study, it was pointed to as a possible independent factor of cerebrovascular risk

Instability of lipoprotein(a) in plasma stored at -70 degrees C: effects of concentration, apolipoprotein(a) genotype, and donor cardiovascular disease.

BACKGROUND: There is considerable evidence to suggest that plasma lipoprotein(a) [Lp(a)] concentration is a cardiovascular risk factor. Confusing results in epidemiologic studies, however, suggest that the effects of storage should be further investigated. The influence of the assay method, the initial plasma Lp(a) concentration, and the apolipoprotein(a) [apo(a)] genotype are all factors that should be considered. METHODS: Blood was obtained from 65 survivors of premature myocardial infarction and 95 age-matched controls. The plasma samples were stored in sterile conditions at -70 degrees C for 5 years in the presence of antioxidant and antiproteolytic substances. Plasma Lp(a) was measured by immunoturbidimetry, and apo(a) alleles were determined by pulsed-field gel electrophoresis and Southern blotting. RESULTS: Plasma Lp(a) was significantly higher in patients. The mean kringle number for the smallest isoform was also lower in patients than in controls, but no differences were found in the distribution of the largest isoform. All patients and controls were heterozygotes. During storage, mean Lp(a) decreased significantly in samples from patients (-23%; P <0.001) but not in samples from controls (-9%; P, not significant). This was not related to the kringle number and was limited to samples with initial plasma Lp(a) concentrations between 41 and 345 mg/L. CONCLUSIONS: Plasma Lp(a) from patients is less stable than Lp(a) from controls, and the difference is not related to distribution of apo(a) genotypes but may be concentration-dependent. Differential sample stability may complicate the interpretation of several studies.

Polymorphisms in human apolipoprotein(a) kringle IV-10 and coronary artery disease: relationship to allele size, plasma lipoprotein(a) concentration, and lysine binding site activity.

Elevated plasma levels of lipoprotein(a) [Lp(a)] represent a major independent risk factor for the development of atherosclerosis. The kringle IV type 10 of apolipoprotein(a) [apo(a)] is the primary lysine binding site (LBS) of Lp(a) and is associated with lesion formation in transgenic mice. The purpose of this study was to search for mutations in the apo(a) kringle IV type 10 which could alter the LBS activity of Lp(a) from patients with coronary artery disease. We found the DNA region of kringle IV type 10 of apo(a) to be mutable but relatively well preserved in the Spanish population. We identified a novel mutation which probably leads to a truncated form of apo(a) in a patient heterozygous for the mutation and with low lysine binding activity and low plasma Lp(a) concentration. Two other mutations have been previously identified in humans, the substitutions W81R and M75T. The W81R was not found in our sample, but the M75T mutation was present in 43% of patients with coronary artery disease and 23% of age-matched controls. The genotype TT conferred a significant risk for myocardial infarction (odds ratio 2.53). This association was not due to linkage disequilibrium with kringle IV repeats. The M75T polymorphism was not associated with the LBS function of apo(a), but it influenced plasma Lp(a) concentration.

Impact of apolipoprotein(a) isoform size heterogeneity on the lysine binding function of lipoprotein(a) in early onset coronary artery disease.

Elevated plasma Lp(a) is an independent risk factor for cardiovascular disease. Unique to Lp(a) is the apoprotein, apo(a) which can vary from 250 to 800 kDa in molecular weight. Small isoforms are also associated with the risk of cardiovascular disease. The purpose of this study was to examine the association of Lp(a) concentration, apo(a) size, and Lp(a) lysine-binding site(s) (LBS) function in patients with early onset heart disease, and age-matched controls. Mean values of Lp(a) were significantly higher in the patients than for the age-matched group. The smallest molecular weight isoform for each subject had significantly fewer kringles for the patients than the age-matched controls. There was a significant correlation between LBS activity and kringle number in the single-banded phenotypes of the patients, but not the controls. LBS activity was significantly higher in patients with small isoforms (< or =18 kringles) compared to controls. The odds ratio for coronary artery disease for high LBS activity and high Lp(a) concentration was 4.4 (p = 0.002) and for high LBS activity and small isoforms was 10.1 (p = 0.002). In the patients, Lp(a) concentration was higher, apo(a) size was smaller, and LBS activity higher in the small isoforms compared to the controls. This study suggests an association of high LBS activity in small isoforms of Lp(a) with disease in humans.

Evaluation of a particle-enhanced turbidimetric immunoassay for the measurement of ferritin: application to patients participating in an autologous blood transfusion program.

OBJECTIVES: To evaluate a turbidimetric immunoassay for the measurement of ferritin, and to assay this method in a group of patients undergoing an autologous blood transfusion program. DESIGN AND METHODS: We used an ILab 900 analyzer. This instrument automates a particle-enhanced immunoturbidimetric assay with an analysis time of 9 min. This technique was compared with a microparticle immunoassay. The turbidimetric assay was used to measure ferritin in a group of 30 patients undergoing an autologous blood transfusion program. RESULTS: The assay was linear in the range 3-1400 microg/L (r = 0.9999). The intra- and inter-assay imprecision (CV) at 20, 97 and 469 microg/L were <3.0 and <5.0%, respectively. Recovery was 88. 7 to 97.4%. The detection limit was 3 microg/L. Hemoglobin (

[Benefits of treatment to eradicate Helicobacter pylori infection in patients with ulcer at a primary care center]. / Beneficios del tratamiento erradicador de la infección por Helicobacter pylori en pacientes ulcerosos en un centro de atención primaria.

OBJECTIVES: To evaluate the clinical evolution and the use of Primary Care health resources one year after treatment to eradicate Helicobacter pylori (Hp) infection in patients with peptic ulcers and Hp infection. DESIGN: Retrospective study on the effect of an intervention. SETTING: Urban, reformed primary care centre. PATIENTS: 102 patients with peptic ulcers and Hp infection. INTERVENTION: Treatment to eradicate Hp. MEASUREMENTS AND MAIN RESULTS: a) Total medical attendance; b) attendance for dyspepsia; c) number of ulcerous outbreaks; d) medicines taken to treat dyspepsia. 79.4% of the patients treated were male. Overall mean age was 47.8 +/- 12.4. After the intervention, total attendance (from 8.3 to 6.6, p < 0.001), attendance for dyspepsia (from 3.1 to 1.1, p < 0.00001), and ulcerous outbreaks (from 1.2 to 0.06, p < 0.00001) all dropped sharply. The mean number of medicines prescribed for dyspepsia per patient fell from 1.24 to 0.43, p < 0.0001. Ranitidine prescription fell from 72.7 to 13.8 days (p < 0.001); and omeprazol from 35.1 to 12.2 days (p < 0.03). Estimated total saving per patient was 26,792 pesetas at 1998 values. CONCLUSIONS: Treatment in primary care to eradicate Hp(+) in ulcerous patients reduced the needs of attendance and the prescription of drugs for ulcers. Just in the first year this supposed a clinical benefit for these patients and important economic savings for the public health service.

Beneficios del tratamiento erradicador de la infección por Helicobacter pylori en pacientes ulcerosos en un centro de atención primaria / Benefits of treatment to eradicate Helicobacter pylori infection in patients with ulcers attending a primary care centre

Objetivo. Evaluar la evolución clínica y la utilización de recursos sanitarios en atención primaria un año después del tratamiento erradicador de Helicobacter pylori (Hp) en pacientes con úlcera péptica e infección por Hp. Diseño. Estudio retrospectivo sobre el efecto de una intervención. Ámbito del estudio. Centro de atención primaria urbano y reformado. Pacientes. Ciento dos pacientes con enfermedad ulcerosa péptica e infección por Hp. Intervención. Tratamiento erradicador de Hp. Mediciones y resultados principales. a) número de visitas totales (VT); b) visitas por dispepsia (VD); c) número de brotes ulcerosos (BU), y d) fármacos consumidos para tratamiento de la dispepsia. De los pacientes tratados un 79,4 por ciento era varón. La edad media global fue de 47,8 ñ 12,4 años. Después de la intervención, disminuyeron significativamente las VT (de 8,3 a 6,6; p < 0,001), las VD (3,1 a 1,1; p < 0,00001), y los BU (de 1,2 a 0,06; p < 0,00001). El número medio de fármacos prescritos para la dispepsia por paciente disminuyó de 1,24 a 0,43 (p < 0,0001). La prescripción de ranitidina pasó de 72,7 a 13,8 días (p < 0,001) y la de omeprazol disminuyó de 35,1 a 12,2 días (p < 0,03). El ahorro total estimado por paciente fue de 26.792 pts. con valores económicos de 1998. Conclusiones. En nuestro medio el tratamiento erradicador en pacientes ulcerosos Hp (+) disminuye las necesidades de asistencia y la prescripción de medicamentos antiulcerosos. Ya durante el primer año esto supone un beneficio clínico para estos pacientes y un ahorro económico importante para la sanidad pública (AU)

Evaluation of a particle-enhanced turbidimetric immunoassay for the measurement of immunoglobulin E in an ILab 900 analyzer.

BACKGROUND: The measurement of immunoglobulin E (IgE) in serum is widely used in the diagnosis of allergic reactions and parasitic infections. We describe here a fully automated assay for human IgE suitable for routine application in a general chemistry analyzer. METHODS: We used an ILab 900 analyzer. This instrument automates a particle-enhanced immunoturbidimetric assay with an analysis time of 9 min. RESULTS: The assay was linear in the range 4-1000 kIU/L (r = 0.9998). The intra- and interassay CVs at 57, 235, and 434 kIU/L were <3.5% and <7.4%, respectively. The detection limit was 4 kIU/L. Hemoglobin (

Plasma homocysteine and the methylenetetrahydrofolate reductase C677T gene variant: lack of association with schizophrenia.

Disturbances in methyl-carbon metabolism, which result in hyperhomocysteinemia, have been associated with schizophrenia. Homozygosity for the T677 allele of the methylenetetrahydrofolate reductase (MTHFR) gene, which encodes for a thermolabile enzyme associated with hyperhomocysteinemia, has been found to be increased in schizophrenic patients. We have investigated whether plasma homocysteine concentration and the frequency of C677T MTHFR variant were increased in schizophrenic inpatients of a psychiatric hospital (n=210) compared with controls (n=218). There were no significant differences in plasma homocysteine concentrations between the schizophrenia and the control group. The distributions of T allele and TT genotype frequencies were similar in both groups (40% and 15%). These results show that impaired homocysteine metabolism is unlikely in schizophrenia.

Lipoprotein(a) and the significance of the association between platelet glycoprotein IIIa polymorphisms and the risk of premature myocardial infarction.

Platelet glycoprotein IIb/IIIa may be involved in the pathogenesis of myocardial infarction as the key element in platelet aggregation and as the binding site of lipoprotein(a) to platelets, inhibiting plasminogen binding and activation. Recently, a strong association between the P1A2 polymorphism of the glycoprotein IIIa gene and acute coronary thrombosis has been reported. although this has not been confirmed. In an associated study, we determined plasma lipoprotein levels, the apo E genotype and the P1A genotype in 250 males under 55 years with myocardial infarction and they were compared with 250 age- and sex-matched controls. Patients showed an over-representation of the epsilon3/4 genotype with respect to the control group. We found that there were no differences in the allelic frequency of P1A2 between case patients and age-matched controls (chi2 = 0.05, P = 0.92) and that subjects bearing the P1A2 allele showed higher plasma lipoprotein(a) concentration than p1A1/P1A1 individuals. Therefore, in this population there is no association between carriage of p1A2 allele and increased risk of myocardial infarction but the carriage of P1A2 is associated with higher plasma Lp(a) concentration.

Evaluation of a homogeneous assay for high-density lipoprotein cholesterol: limitations in patients with cardiovascular, renal, and hepatic disorders.

We evaluated the performance of a homogeneous assay for the automated measurement of high-density lipoprotein cholesterol (HDL-C) and compared it with a conventional precipitation technique in the following groups of people: control subjects (group A), clinically-healthy elderly (group B), myocardial infarction patients (group C), nephrotic syndrome patients (group D), and liver cirrhosis patients (group E). The performance of the technique was acceptable with respect to precision, accuracy, linearity, and detection limit. Triglycerides up to 40 mmol/L and bilirubin up to 150 micromol/L did not cause interferences. Hemoglobin decreased HDL-C measurements. Samples were stable at -20 degrees C for up to four months. Bland-Altman plots showed a good agreement between both techniques in the control group but with a progressive divergence in the patient groups B to E. Results indicate limitations of the technique in certain clinical conditions and, coincidentally, the need for reliable calibration materials.

The influence of hypoalbuminemia in the generation of nephrotic hyperlipidemia.

Lipoprotein measurements in a group of 29 patients with massive proteinuria and without hypoalbuminemia, were compared with those observed in matched controls and patients with overt nephrotic syndrome to assess the influence of plasma albumin concentration and proteinuria in modulating blood lipid levels. Plasma apoprotein B and apo B containing lipoproteins were not increased in proteinuric normoalbuminemic patients. There was a good correlation between plasma albumin and oncotic pressure (r = 0.937; P < 0.001). Plasma oncotic pressure was inversely correlated with plasma apoprotein B in nephrotic patients (r = -0.44, P = 0.017) but not in normoalbuminemics (r = 0.17, P = 0.369), suggesting that plasma albumin affects apoprotein B secretion. Other findings, however, indicate that multiple processes are ocurring simultaneously in these patients. There was an accumulation of very low- and intermediate density lipoproteins in normoalbuminemics, suggesting a residual defect in the lipoprotein removal. Also, raised (P < 0.05) lipoprotein(a) levels respect to controls (median, 0.15 g/l) were noted in both, normoalbuminemics (median, 0.72 g/l) and hypoalbuminemics (median, 0.84 g/l) with similar degree of proteinuria (6.4 vs. 6.6 g/24 h), suggesting that other mechanisms may be operative in lipoprotein(a) derangements. Our findings suggest that there is no unique mechanism in the pathogenesis of nephrotic hyperlipidemia but that both hypoalbuminemia and proteinuria can have a distinct contribution, individually or in combination.