Primary Aldosteronism and Drug Resistant Hypertension: A "Chicken-Egg" Story.

Drug-resistant arterial hypertension (RH) is a major risk factor for cardiovascular disease, often due to overlooked underlying causes. Identification of such causes poses significant clinical challenges. In this setting, primary aldosteronism (PA) is a frequent cause of RH and its prevalence in RH patients is likely higher than 20%.The pathophysiological link between PA and the development and maintenance of RH involves target organ damage and the cellular and extracellular effects of aldosterone excess that promote pro-inflammatory and pro-fibrotic changes in the kidney and vasculature.The feasibility of adrenal vein sampling in PA patients with RH, and the clinical benefit achieved by adrenalectomy, further emphasize the need to implement systematic screening for this common form of secondary hypertension in the management of a high-risk population as RH patients.: We herein review the current knowledge of the factors that contribute to the RH phenotype with a focus on PA and discuss the issues regarding the screening for PA in this setting and the therapeutic approaches (surgical and medical) aimed at resolving RH caused by PA.

A novel MRPS34 gene mutation with combined OXPHOS deficiency in an adult patient with Leigh syndrome.

We report a novel pathogenic variant (c.223G > C; p.Gly75Arg) in the gene encoding the small mitoribosomal subunit protein mS34 in a long-surviving patient with Leigh Syndrome who was genetically diagnosed at age 34 years. The patient presented with delayed motor milestones and a stepwise motor deterioration during life, along with brain MRI alterations involving the subcortical white matter, deep grey nuclei and in particular the internal globi pallidi, that appeared calcified on CT scan. The novel variant is associated with a reduction of mS34 protein levels and of the OXPHOS complex I and IV subunits in peripheral blood mononuclear cells of the case. This study expands the number of variants that, by affecting the stability of the mitoribosome, may cause an OXPHOS deficiency in Leigh Syndrome and reports, for the first time, an unusual long survival in a patient with a homozygous MRPS34 pathogenic variant.

SARS CoV2 infection in a young subject affected by arginosuccinate synthase deficiency: A case report of epilepsy worsening.

We describe a case of a 21 years old woman affected by Citrullinemia type 1- Arginosuccinate Synthase deficiency (ASSD)-who underwent a SARS CoV2 infection during the first phase of pandemic burst in Italy. She had no symptoms of infection nor a metabolic crisis. After recovery from SARS CoV2, she experienced a worsening in their epilepsy despite therapy, with one/two crisis a week.

Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA2 and cardiovascular diseases.

BACKGROUND: A large number of observational epidemiological studies have reported generally positive associations between circulating mass and activity levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular diseases. Few studies have been large enough to provide reliable estimates in different circumstances, such as in different subgroups (e.g., by age group, sex, or smoking status) or at different Lp-PLA2 levels. Moreover, most published studies have related disease risk only to baseline values of Lp-PLA2 markers (which can lead to substantial underestimation of any risk relationships because of within-person variability over time) and have used different approaches to adjustment for possible confounding factors. OBJECTIVES: By combination of data from individual participants from all relevant observational studies in a systematic 'meta-analysis', with correction for regression dilution (using available data on serial measurements of Lp-PLA2), the Lp-PLA2 Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age and sex-specific associations of plasma Lp-PLA2 with coronary heart disease (and, where data are sufficient, with other vascular diseases, such as ischaemic stroke). It will also help to determine to what extent such associations are independent of possible confounding factors and to explore potential sources of heterogeneity among studies, such as those related to assay methods and study design. It is anticipated that the present collaboration will serve as a framework to investigate related questions on Lp-PLA2 and cardiovascular outcomes. METHODS: A central database is being established containing data on circulating Lp-PLA2 values, sex and other potential confounding factors, age at baseline Lp-PLA2 measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of Lp-PLA2 and potential confounding factors has been sought to allow adjustment for possible confounding and correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available observational studies of Lp-PLA2 will yield information on a total of about 15 000 cardiovascular disease endpoints.

Immunocomplexes and primary lung cancer.

Circulating immune complexes (CIC) were found in 47% of 71 patients before treatment, in a horizontal study of the presence of CIC in primary lung cancer (PLC). The precipitation technique in PEG was used, and C1q, IgG and IgM fractions in the precipitate were assayed. Especially in epidermoid carcinoma, CIC were found in 1/6 cases with stage 1, 2/9 with stage II and 21/34 with stage III. The frequency was significantly higher in stage III cases, and showed a significant tendency to increase with progression of the clinical stage. If stage parameters are considered separately, this tendency correlates significantly (p less than 0.002) with the amount of lymph node involvement (N) but not to the tumor (T) size nor to the presence of metastases (M). Analysis of CIC behavior in comparison with the single fractions showed that C1q and/or IgG were elevated in 40% of cases. The presence of C1q and/or IgG associated with IgM is more characteristic of stage N2, while the presence of CIC with the fractions C1q and/or IgG not associated with IgM is more frequent in stage N1. There was a lower survival rate at 12 months in patients with CIC as compared to those without (p less than 0.05).

Studies on bronchoalveolar cells in human diseases. II. General morphology and ultrastructure of pulmonary macrophages and small mononuclear cells in sarcoidosis.

Data are presented from light and electron microscopic studies on bronchoalveolar lavage (BAC) in sarcoidosis, with particular emphasis on the ultrastructural morphology and functional characteristics of pulmonary macrophages (PM) and small mononuclear cells (SMC). Light microscopy showed an average of over 77% of the BAC to be PM, range 99-51%. SMC populations were also extremely variable. These variations may relate directly to the degree of disease activity. Electron microscopy demonstrated a wide range of morphological and implied functional (biosynthetic and phagocytic) characteristics of PM. Some of these are morphologically comparable to cells found in tissue granulomata. Our ultrastructural study has shown that the SMC population is made up of lymphocytes, monocytes and cells with intermediate characteristics (precursors).

Studies on bronchoalveolar cells in humans. I. Preliminary morphological studies in various respiratory diseases.

A preliminary investigation has been carried out on bronchoalveolar cells obtained following lavage in various respiratory diseases. Of 23 cases observed, 7 have been studied in detail, 6 cases provided insufficient material for investigation, and the data obtained from the remaining 10 cases were inconclusive. Considerations are made with regard to the value of bronchial lavage in clinical diagnosis and cell studies.

The spectrum of human tuberculosis.

Clinical, morphological and immunological studies of human tuberculosis have enabled the spectrum of the disease to be determined. We have investigated the cell-mediated immune responses by means of skin tests and leucocyte migration inhibition to PPD, and the humoral immune responses by means of immunodiffusion and haemagglutination tests. Patients with tuberculosis can be classified into two polar groups--reactive (RR) and unreactive (UU), the former showing good cell-mediated immunity and little or no antibody formation and the latter poor cellular responses and exuberant antibody production. The intermediate forms show characteristics of the neighbouring polar groups. The existence of a spectrum of immune response in tuberculosis, which has long been suspected, is now demonstrated.

Immunological aspects of sarcoidósis.

The results are reported of an immunological study conducted on 37 cases of active sarcoidosis, in which some in vivo and in vitro tests related to the cell-mediated immunitary response were effected. The results are discussed, with relation to the clinical use of the immunological tests adopted, and their immunopathogenetic significance. In particular, the occurrence of false-positive and false-negative results in the in vitro Kveim antigen test (LMT) using the antigen preparations currently available, limit its use in clinical practice.

[Immunological diagnosis of hilarmediastinal lymphadenopathies (author's transl)]. / Sulla diagnostica immunologica delle linfoadenopatie ilomediastiniche

In the last few years, we have adopted the following immunological techniques for the study of hilarmediastinal lymphadenopathies: the E and EAC rosette tests (composition of the lymphocyte population) for an evaluation of the general immunological picture, the delayed-type cutaneous tests to reveal the specific picture of cell-mediated immune responses, and the leucocyte migration inhibition test against related and unrelated antigens. This cellular technique was integrated with the determination of precipitating and agglutinating antibodies against the same antigens. Data are reported regarding tubercular and sarcoid lymphadenopathies, Hodgkin's disease, and secondary neoplastic lymphadenopathy with prevalent intratoracic localization. The techniques used demonstrated that tubercular lymphadenopathy is associated with a well defined immunological profile which is both humoral and cellular. Sarcoid lymphadenopathy (thoracic sarcoidosis) showed a specific, well characterized immunological picture as regards cell-mediated immune responses. In Hodgkin's disease (hilarmediastinal lymphadenopathy) the immunological technique showed up a general, depressed immunological picture, particularly as regards the cell-mediated immunitary response, presumably partly due to the treatment given (physical and pharmacological therapy). Secondary neoplastic lymphadenopathy showed a similar pattern, as far as the immunological parameters used until now are concerned. On the basis of experience gained to date, we believe that the immunological techniques can make a contribution to diagnostic and clinical studies of tubercular and sarcoid lymphadenopathies.

[Studies of cellular sensitization to BCG and PPD using leukocyte cell migration inhibition]. / Rilievo della sensibilizzazione cellulare al BCG ed al PPD mediante il test di inibizione della migrazione leucocitaria

Leucocyte inhibition migration test (LMT) with BCG and PPD was applied in pulmonary tuberculosis, lung cancer and sarcoidosis. No significant differences were noticed in the results obtained with each of the two antigenic materials; nevertheless, one case lobectomized of lung cancer successively treated with chemiotherapie and immunostimulation with BCG presented LMT positivity with BCG and negativity with PPD. The unpublished results of the former investigations carried out with brute tuberculin (LMT) on patients with pulmonary tuberculosis are here reported no significant difference was noticed between the results obtained with brute tuberculin, and the results with PPD. The still unsettled problem presented by the lack of inhibition in the presence of PPD in leucocyte migration test in patients with areactive (AA) and intermediate areactive (AI) tuberculosis is also briefly discussed. Finally, the existence of a dissociation between the cutaneous delayed test and the in vitro test for the detection of cellular sensibilisation is confirmed even when LMT is applied either in the presence of BCG or of PPD.