New perspectives in the management of public health systems

The following pages try to offer some ways of arguing against pesimism in our health administration culture. In fact, the review of a wide range of feasible reforms of our health system undertaken in this paper gives some clues for a better implementation of the a priori advantages of public health systems. These advantages are not achieved today because of some dysfunctionalities of daily management. To rationalize resources distribution, to evaluate the results, to eliminate unnecessary administrative control, to coordinate responsibility and budgeting centers, to introduce free choice as a response to public demand, and to simulate marketing by private production of public services are elements suggested in this paper to improve public health services management.     

Transthyretin amyloidosis with cardiomyopathy after domino liver transplantation: Results of a cross-sectional study

Domino liver transplantation (DLT) has been used widely in patients with hereditary amyloid transthyretin (ATTR) amyloidosis. New-onset polyneuropathy in recipients of DLT has been reported, but there are few cases of cardiac involvement reported. We aimed to perform a cross-sectional study for ATTR amyloidosis with cardiomyopathy (ATTR-CM) in DLT recipients. We evaluated 23 living DLT recipients a median of 9 years since DLT at 2 referral centers with a systematic cardiac evaluation, including bone scintigraphy. Median age was 72 years, 91% had hypertension, 35% had diabetes mellitus, 67% had chronic renal failure, and 8 patients (35%) developed new-onset polyneuropathy. Only 13% had a normal electrocardiogram and a normal echocardiography, and most of them showed some conduction disturbance or increase in left ventricular wall thickness, but only 1 patient with a Glu89Lys mutation developed ATTR-CM diagnosed by bone scintigraphy and endomyocardial biopsy. None of the recipients of a DLT with Val30Met mutation showed cardiac involvement by bone scintigraphy. In conclusion, DLT from Val30Met donors seems to be safe regarding the development of ATTR-CM. Evaluation of cardiomyopathy in DLT recipients is challenging due to concomitant comorbidities and in this context, bone scintigraphy can be helpful to evaluate ATTR-CM.     

Immunological classification of acute myeloblastic leukemias: relevance to patient outcome.

Immunophenotyping is a major tool to assign acute leukemia blast cells to the myeloid lineage. However, because of the large heterogeneity of myeloid-related lineages, no clinically relevant immunological classification of acute myeloblastic leukemia (AML) has been devised so far. To attempt at formulating such a classification, we analyzed the pattern of expression of selected antigens, on blast cells collected at AML diagnosis. Patients were eligible if they had a first diagnosis of de novo AML and a sufficient number of blast cells for proper immunophenotyping. The relative expression of CD7, CD13, CD14, CD15, CD33, CD34, CD35, CD36, CD65, CD117, and HLA-DR were analyzed by cytometry in a test series of 176 consecutive AML cases. Statistical tools of clusterization allowed to remove antigens with overlapping distribution, leading us to propose an AML classification that was validated in a second AML cohort of 733 patients. We identified five AML subsets (MA to ME) based on the expression of seven antigens within four groups (CD13/CD33/CD117, CD7, CD35/CD36, CD15).-MA and MB-AML have exclusively myeloid features with seldom extramedullary disease and rare expression of lymphoid antigens. No cases of acute promyelocytic leukemia (APL) were observed within MB AML. MC AML have either myeloid or erythroblastic features. MD AML have more frequently high WBC counts than other subsets, which were related to the expression of CD35/CD36 and CD14 and to monoblastic differentiation. ME AML lack CD13, CD33, and CD117 but display signs of terminal myeloid differentiation. Specific independent prognostic factors were related to poor overall survival in each immunological subset: CD34+ (P<3 x 10(-4)) in MA AML, CD7+ in MB AML, non-APL cases (P<0.03) in MC AML, CD34+ (P<0.002) and CD14+ (P<0.03) in MD AML, CD14+ in ME AML (P<0.01). The inclusion of seven key markers in the immunophenotyping of AML allows a stratification into clinically relevant subsets with individual prognostic factors, which should be considered to define high-risk AML populations.     

Control of cholesterolemia in Spain, 2000. A tool for cardiovascular prevention

The document "Cholesterolemia Control in Spain, 2000: A Tool for Cardiovascular Disease Prevention" reviews the current evidence on cardiovascular disease prevention and the therapeutic advances achieved in recent years, in order to aid risk-based clinical decision-making. Cardiovascular diseases rank as the first cause of death in Spain. Their demographic, health and social impact is increasing and it is likely to continue to do so in the next decades. Appropriate treatment for high blood cholesterol and other major risk factors is crucial in cardiovascular disease prevention. Individual risk stratification is essential to determine follow-up periodicity and treatment. Priorities for the control of cholesterolemia and the consequent cardiovascular risk are based on risk stratification. In primary prevention, the therapeutic objective in high risk patients has been established as LDL-cholesterol < 130 mg/dl. In secondary prevention, drug treatment is indicated when LDL-cholesterol > or = 130 mg/dl and the therapeutic objective is LDL-cholesterol < 100 mg/dl. Statins are first line drugs for treatment of high blood cholesterol. In moderate-severe hypertriglyceridemia or low HDL-cholesterol, fibrates are preferred. In acute coronary syndrome, hypolipemiant treatment, should be started as soon as possible, when indicated. Secondary prevention programmes that continually provide good clinical and risk factor control should be provided to coronary heart disease patients.     

Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19 patients

SARS-CoV-2 infection causes an abrupt response by the host immune system, which is largely responsible for the outcome of COVID-19. We investigated whether the specific immune responses in the peripheral blood of 276 patients were associated with the severity and progression of COVID-19. At admission, dramatic lymphopenia of T, B, and NK cells is associated with severity. Conversely, the proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh) and CD56^–CD16⁺ NK-cells increased. Regarding humoral immunity, levels of IgM, IgA, and IgG were unaffected, but when degrees of severity were considered, IgG was lower in severe patients. Compared to healthy donors, complement C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, while the activation peptide of C5 (C5a) increased from the admission in every patient, regardless of their severity. Moreover, total IgG, the IgG1 and IgG3 isotypes, and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Our study provides important clues to understand the immune response observed in COVID-19 patients, associating severity with an imbalanced humoral response, and identifying new targets for therapeutic intervention.     

Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma. A clinicobiological study of the GELA

Background In angioimmunoblastic T-cell lymphoma, symptoms linked to B-lymphocyte activation are common, and variable numbers of CD20(+) large B-blasts, often infected by Epstein-Barr virus, are found in tumor tissues. We postulated that the disruption of putative B-T interactions and/or depletion of the Epstein-Barr virus reservoir by an anti-CD20 monoclonal antibody (rituximab) could improve the clinical outcome produced by conventional chemotherapy. DESIGN AND METHODS: Twenty-five newly diagnosed patients were treated, in a phase II study, with eight cycles of rituximab + chemotherapy (R-CHOP21). Tumor infiltration, B-blasts and Epstein-Barr virus status in tumor tissue and peripheral blood were fully characterized at diagnosis and were correlated with clinical outcome. RESULTS: A complete response rate of 44% (95% CI, 24% to 65%) was observed. With a median follow-up of 24 months, the 2-year progression-free survival rate was 42% (95% CI, 22% to 61%) and overall survival rate was 62% (95% CI, 40% to 78%). The presence of Epstein-Barr virus DNA in peripheral blood mononuclear cells (14/21 patients) correlated with Epstein-Barr virus score in lymph nodes (P<0.004) and the detection of circulating tumor cells (P=0.0019). Despite peripheral Epstein-Barr virus clearance after treatment, the viral load at diagnosis (>100 copy/μg DNA) was associated with shorter progression-free survival (P=0.06). Conclusions We report here the results of the first clinical trial targeting both the neoplastic T cells and the microenvironment-associated CD20(+) B lymphocytes in angioimmunoblastic T-cell lymphoma, showing no clear benefit of adding rituximab to conventional chemotherapy. A strong relationship, not previously described, between circulating Epstein-Barr virus and circulating tumor cells is highlighted.     

Comparison study of full and subthreshold bulimia nervosa: Personality,clinical characteristics,and short-term response to therapy

Abstract

This study compared symptomatological and personality differences between individuals with threshold bulimia nervosa (BN; n=39) and those with subthreshold BN (n=39) and their short-term response to a brief outpatient intervention. Participants were matched using a pairwise matching procedure, taking into account age, age of onset, and duration of the disorder. Both groups received the same brief outpatient psychoeducational therapy. The same assessment measures were used before and after treatment. With the exception of some clinical and psychopathological symptoms (higher depression and phobic anxiety in threshold BN), there were no significant between-group differences on scales of general psychopathology or personality traits. At the end of treatment, there were no significant between-group differences on abstinence rates for binge eating and vomiting, number of sessions attended, or dropout rates. Threshold BN and subthreshold BN share common psychopathological symptoms and personality traits. No differences in therapy outcome were observed for the two groups after a brief group psychoeducational intervention.