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.

Retroperitoneal abscess after urgent resection of the stomach in a geriatric patient treated with a surgical extraperitoneal approach - case report.

Retroperitoneal abscess after abdominal and retroperitoneal surgery is a relatively rare but serious complication that most often occurs as a result of a healing disorder in the postoperative period. The incidence is not high, in the literature the cases are mostly reported as case reports with a serious clinical course, high morbidity and mortality. The most important factor of effective treatment, after successful diagnosis by CT examination is rapid evacuation of the abscess and retroperitoneal drainage, in which mini-invasive surgical or radiological drainage dominate as methods of choice. Surgical drainage, burdened by higher morbidity and mortality is considered the last resort after failure of mini-invasive methods. In our case report, we present a case of retroperitoneal abscess, arising as a complication after gastric resection, which was evacuated and drained primarily surgically due to unsuitability for radiological intervention.

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.

Malignant Mesothelioma of the Tunica Vaginalis Testis. A Clinicopathologic Analysis of Two Cases with a Review of the Literature.

Paratesticular malignant mesothelioma is an extremely rare type of mesothelioma with only a limited number of reported cases. Its clinical differentiation is challenging, and its diagnosis is almost exclusively accidental. The major risk factor is exposure to asbestos, typically with a long latency between exposure and diagnosis. The current study presents the clinical data of two patients diagnosed with paratesticular malignant mesothelioma. We evaluated a large spectrum of risk factors in the patients histories. The histomorphological and immunohistochemical characteristics were analysed and put into the perspective of a broad differential diagnosis. Both cases of malignant epithelial mesothelioma of the tunica vaginalis testis clinically presented as unilateral hydroceles. Patients underwent surgery with the perioperative finding of a tumour. Radical inguinal orchiectomy was the treatment of choice for both patients. After comprehensive staging, the second patient underwent a second step of inguinal and pelvic lymph node dis- section. Follow-up visits revealed recurrence of the disease in the first patient. Resection of the tumour was performed. The histology confirmed the relapse of a tumour with identical features to those of the first tumour. Chemotherapy and radiotherapy were not indicated. Both patients are currently in complete remission. In conclusion, surgical treatment had a determinative role in the prognosis of these patients. Radical orchiectomy is the treatment of choice for localized disease. Lymph node dissection can be considered in the case of lymph node enlargement. There is a lack of evidence-based data for adjuvant chemotherapy and radiotherapy. Patients should be referred to experienced multidisciplinary cancer centres for a second opinion on histology, treatment, and a follow-up plan.Key words: mesothelioma - tunica vaginalis testis - hydrocele - asbestos exposure.

Performance of dose calculation algorithms from three generations in lung SBRT: comparison with full Monte Carlo-based dose distributions.

The accuracy of dose calculation is a key challenge in stereotactic body radiotherapy (SBRT) of the lung. We have benchmarked three photon beam dose calculation algorithms--pencil beam convolution (PBC), anisotropic analytical algorithm (AAA), and Acuros XB (AXB)--implemented in a commercial treatment planning system (TPS), Varian Eclipse. Dose distributions from full Monte Carlo (MC) simulations were regarded as a reference. In the first stage, for four patients with central lung tumors, treatment plans using 3D conformal radiotherapy (CRT) technique applying 6 MV photon beams were made using the AXB algorithm, with planning criteria according to the Nordic SBRT study group. The plans were recalculated (with same number of monitor units (MUs) and identical field settings) using BEAMnrc and DOSXYZnrc MC codes. The MC-calculated dose distributions were compared to corresponding AXB-calculated dose distributions to assess the accuracy of the AXB algorithm, to which then other TPS algorithms were compared. In the second stage, treatment plans were made for ten patients with 3D CRT technique using both the PBC algorithm and the AAA. The plans were recalculated (with same number of MUs and identical field settings) with the AXB algorithm, then compared to original plans. Throughout the study, the comparisons were made as a function of the size of the planning target volume (PTV), using various dose-volume histogram (DVH) and other parameters to quantitatively assess the plan quality. In the first stage also, 3D gamma analyses with threshold criteria 3%/3mm and 2%/2 mm were applied. The AXB-calculated dose distributions showed relatively high level of agreement in the light of 3D gamma analysis and DVH comparison against the full MC simulation, especially with large PTVs, but, with smaller PTVs, larger discrepancies were found. Gamma agreement index (GAI) values between 95.5% and 99.6% for all the plans with the threshold criteria 3%/3 mm were achieved, but 2%/2 mm threshold criteria showed larger discrepancies. The TPS algorithm comparison results showed large dose discrepancies in the PTV mean dose (D50%), nearly 60%, for the PBC algorithm, and differences of nearly 20% for the AAA, occurring also in the small PTV size range. This work suggests the application of independent plan verification, when the AAA or the AXB algorithm are utilized in lung SBRT having PTVs smaller than 20-25 cc. The calculated data from this study can be used in converting the SBRT protocols based on type 'a' and/or type 'b' algorithms for the most recent generation type 'c' algorithms, such as the AXB algorithm.

Integration of the e-Learning into the medical university curricula.

OBJECTIVES: The aim of this contribution was to present the e-Learning introduction in the Slovak Medical University (SMU) with a focus on the implementation phase of the two blended courses - Healthcare Quality and Healthcare Professionals' Ethics. BACKGROUND: The introduction of the e-Learning was realized during the period 2008-2009 in the partnership of SMU and IBM Company, following strictly the project management approach. METHODS: The development of the e-module beta-versions was evaluated by the modules' authors using a structured interview. In a consequent pilot testing, the blended courses were evaluated by 23 students of the bachelor program in Rescue health care, and by 61 public health students at the master level program, respectively, using the standardized questionnaires. RESULTS: The tangible results included the documented SMU strategy for the e-Learning integration, six e-Learning modules and evaluation results. The authors' evaluation showed high scores for the experience in collaboration with IBM, as well as for the experience with the LMS environment. The students' evaluation showed a high acceptance of the e-Learning by both part-time and full-time students. The access to Internet was not recognized as a serious barrier. CONCLUSION: The first experience with the integration of the e-Learning into the curricula of the Slovak Medical University showed the advantage of the systematic approach. The experience with developing the strategy in an interdisciplinary/ intercultural team, the knowledge about specific characteristics of distance learning by the involved SMU staff, and the know-how and skills represented the important benefits. It was demonstrated that the blended learning is recommended as optimal for the education in medical environment (Tab. 4, Fig. 1, Ref. 22).

Early changes in osteochondral tissues in a rabbit model of post-traumatic osteoarthritis.

Concurrent osteoarthritic (OA) manifestations in bone and cartilage are poorly known. To shed light on this issue, this study aims to investigate changes in subchondral bone and articular cartilage at two time points after anterior cruciate ligament transection (ACLT) in a rabbit model. 2 (N = 16) and 8 (N = 10) weeks after ACLT, the subchondral bone structure, cartilage thickness, Osteoarthritis Research Society International (OARSI) score, fixed charged density (FCD), and collagen orientation angle were analyzed. OA related changes were evaluated by comparing the ACLT to the contralateral (C-L) and control knees. Already 2 weeks after ACLT, higher trabecular number in the medial femoral condyle and femoral groove, greater OARSI score in the femoral condyles, and thinner trabeculae in the lateral tibial plateau and femoral groove were observed in ACLT compared to C-L knees. Only minor changes of cartilage collagen orientation in the femoral condyles and femoral groove and smaller FCD in the femoral condyles, medial tibial plateau, femoral groove and patella were observed. 8 weeks post-ACLT, the surgical knees had thinner subchondral plate and trabeculae, and smaller trabecular bone volume fraction in most of the knee locations. OARSI score was greater in the femoral condyle and lateral tibial plateau cartilage. FCD loss was progressive only in the femoral condyle, femoral groove, and patellar cartilage, and minor changes of cartilage collagen orientation angle were present in the femoral condyles, femoral groove, and lateral tibial plateau. We conclude that ACLT induces progressive subchondral bone loss, during which proteoglycan loss occurs followed by their partly recovery, as indicated by FCD results.

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.

A randomized trial on the effect of mannitol on postoperative renal function in patients with obstructive jaundice.

A randomized trial was undertaken to reassess the effectiveness of mannitol in preventing postoperative renal impairment in patients with obstructive jaundice. The study included 31 patients with obstructive jaundice (bilirubin, 3 mg/dl or higher) randomly allocated in two groups to receive (n = 17) or not receive (n = 14) preoperative mannitol. Sixty-five percent of patients had a creatinine clearance below 70 ml/min before surgery. Serum bilirubin and bacteribilia had no relation with preoperative renal function. No relation was found between serum bilirubin value and the percentage fall in postoperative creatinine clearance. Compared with the preoperative values, the postoperative creatinine clearance was significantly impaired in the mannitol group (p = 0.03) and remained almost unaltered in the no-mannitol group. Three patients (9.7%) died of acute renal failure; two were in the mannitol group and one was in the no-mannitol group. Serum fibrin degradation products were not sensitive markers for impending renal failure. There was no significant difference in postoperative serum sodium concentration or in the urinary sodium excretion. Administration of mannitol did not improve the postoperative renal function of jaundiced patients, nor did it prove beneficial in preventing renal failure. Our results suggest that severe disturbances of body-fluid compartments may be the basic mechanism underlying kidney dysfunction in obstructive jaundice and that further water depletion induced by mannitol may indeed prove detrimental.

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.

Congenital giant hydronephrosis in adults.

Giant hydronephrosis is the term designating the presence of more than 1,000 ml. of fluid in the collecting system. Of 4 cases of congenital hydronephrosis found over a three-year period at the Ochsner Medical Institutions, 2 were associated with unsuspected carcinomas. Hydronephrosis may first be detected as a mass palpable in the abdomen and displacing the intestines on gastrointestinal films. Excretory urography, retrograde pyelography, and angiography confirm the diagnosis. The treatment of choice is nephrectomy.

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 (

Numerical instabilities in bone remodeling simulations: the advantages of a node-based finite element approach.

Long bone structure occurs in two distinct forms. The bone mass near the joint is primarily found in a distributed, porous trabecular structure, while in the diaphyses a tubular cortical structure is formed. It seems likely that these two observed morphologies come about, at least in part, as a mechanical adaptation to the different mechanical demands in the two regions. Mathematical formulations of this dependency have been proposed, thus facilitating numerical simulations of bone adaptation. Recently two types of discontinuities have been observed in these simulations. The first type (near-field) appears in areas near distributed load application and is characterized by a 'checkerboard' pattern of density wherein adjacent remodeled elements alternate between low and high density. The second type of discontinuity (far-field) appears remote from the load application and is characterized by strut or column-like regions of elements which become fully compact bone while adjacent regions are fully resorbed. In fact, the far-field discontinuity is an accurate representation of bone physiology and morphology since it is consistent with the appearance of cortical bone in the diaphysis. On the other hand, the near-field discontinuity, appears in a region where continuous distributions of intermediate apparent densities (trabecular bone) are expected. This finding may cause some to question whether a single continuum formulation of bone remodeling can predict both discontinuous far-field behavior and continuous near-field behavior. We describe a node-based implementation of current continuum bone remodeling theories which eliminates the spurious near-field discontinuities and preserves the anatomically correct far-field discontinuities, thus indicating that a single biological process may be at work in forming and maintaining both far-field and near-field morphologies.

Adaptive bone remodeling incorporating simultaneous density and anisotropy considerations.

Over 100 years ago, Wolff hypothesized that cancellous bone altered both its apparent density and trabecular orientation in response to mechanical loads. A mathematical counterpart of this principle is derived by adding a remodeling rule for the rate-of-change of the full anisotropic stiffness tensor (all 21 independent terms) to the density rate-of-change rule adapted from an existing isotropic theory. As a result, anisotropy and density patterns develop such that the local stiffness tensor is optimal for the given series of applied loadings. The method does not rely on additional morphological measures of trabecular orientation. Furthermore, assumptions of material symmetry are not required, and any observed regions of orthotropy, transverse isotropy, or isotropy are a result entirely of the functional adaptation of the bone and not the consequence of a modeling assumption. This approach has been implemented with the finite element method and applied to a two-dimensional model of the proximal femur with encouraging results.

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.

High cervical disc herniation and Brown-Sequard syndrome. A case report and review of the literature.

We describe a rare herniation of the disc at the C2/C3 level in a 73-year-old woman. It caused hemicompression of the spinal cord and led to the Brown-Sequard syndrome. The condition was diagnosed clinically and by MRI six months after onset. Discectomy and fusion gave complete neurological resolution.