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.

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.

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.

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.

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.

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.

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 (

Serum fructosamine concentration in patients with nephrotic syndrome and with cirrhosis of the liver: the influence of hypoalbuminaemia and hypergammaglobulinaemia.

We have investigated the influence of variation of the concentrations of serum albumin and immunoglobulins on serum fructosamine concentration in 33 patients with nephrotic syndrome, and 18 patients with cirrhosis of the liver. Protein alterations were evident in these patients and they were compared with 109 normal subjects, 43 patients with type II diabetes mellitus and nine diabetic patients with nephrotic syndrome. The mean serum fructosamine concentration in diabetic patients (2.76 +/- 0.53 mmol/L) was significantly increased (P less than 0.001) by comparison with normal subjects (1.93 +/- 0.20 mmol/L) and the other patients studied. Patients with diabetic nephropathy had higher (P less than 0.01) serum fructosamine concentrations (2.23 +/- 0.54 mmol/L) than non-diabetic patients with the nephrotic syndrome (1.57 +/- 0.37 mmol/L) but remained with the normal range. Positive correlations were observed between fructosamine and immunoglobulins G and M in nephrotic and cirrhotic patients. Serum immunoglobulin A was also directly correlated with serum fructosamine in patients with cirrhosis of the liver. An inverse correlation between albumin and fructosamine in serum of patients with cirrhosis of the liver was also noted. We conclude that the fructosamine assay is not useful in the assessment of glycemic control in patients with cirrhosis of the liver, nephrotic syndrome or in any other clinical situation in which protein metabolism is altered.

[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.

Automated latex agglutination immunoassay of serum ferritin with a centrifugal analyzer.

A considerable demand for convenient, rapid, inexpensive assays of ferritin in serum has been generated in recent years in hospital laboratories and blood banks. We describe a simple and rapid particle-enhanced turbidimetric immunoassay suitable for routine application in a Monarch 2000 centrifugal analyzer with commercially available reagents. This fully automated assay (y) requires no pretreatment of sample, and correlation with a two-step sandwich ELISA (x) is excellent (y = 1.018x + 0.397, Sy/x = 0.027). The analytical range extends from 5 to 900 micrograms/L. Intraassay imprecision (CV) ranged from 1.1% to 5% for various specimen concentrations. Interassay imprecision ranged from 2.2% for above-normal concentrations (755 micrograms/L) to 9.5% for low concentrations (39 micrograms/L). No specimen-related carryover was detected. The method has been useful in our predeposit autologous blood transfusion program for rapid assessment of iron status in patients undergoing repeated phlebotomies.

Accumulation of atherogenic remnants and lipoprotein(a) in the nephrotic syndrome: relation to remission of proteinuria.

Although lipoprotein abnormalities of the nephrotic syndrome are assumed to be related to the presence of proteinuria, this topic has not been investigated extensively. We measured lipoproteins from 19 nonuremic patients during and after remission of the nephrotic syndrome in an effort to determine the extent of their putative atherogenicity. As expected, disturbances involved primarily the apoprotein B-containing lipoproteins. No patient showed serum lipoprotein(a) [Lp(a)] < 300 mg/L during the acute phase. Lp(a) concentrations correlated significantly with those of apoprotein B, and both values decreased dramatically with the remission of the nephrotic syndrome. Surprisingly, despite the resolution of proteinuria, concentrations of intermediate-density lipoproteins and Lp(a) remained above normal in hypertriglyceridemic patients, suggesting a residual effect of nephrosis in the overall lipoprotein transport. Accumulation of atherogenic remnants should be considered a characteristic of the hyperlipidemia of the nephrotic syndrome, and aggressive treatment to reduce proteinuria is mandatory.

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 (

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.

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.