EFFECTS OF THYROTROPIN AND THYROID HORMONES ON THE ENDOTHELIUM IN THYROID DYSFUNCTIONS

Background: The relationship between thyroid hormones and cardiovascular system has been extensively analyzed in experimental and clinical studies in overt and subclinical thyroid dysfunctions. Endothelium and vascular smoot-muscle cells are biological target of thyroid hormones action and their role have been investigated in hypothyroidism and hyperthyroidism. On the contrary the potential pathophysiological role of thyrotropin (TSH) on the cardiovascular system has been poorly investigated. The studied conducted so far to assess the direct effects of TSH in the peripheral vascular endothelium in thyroidectomized patients produced conflicting results. Moreover the effect of TSH on coronary endothelial cells has never directly studied in humans before our study. Aim of the study: The present study was designed to investigate the endothelial response of coronary flow to recombinant human TSH (rhTSH) in patients with differentiated thyroid cancer (DTC) without cardiovascular risk factors to assess the direct effects of TSH on coronary endothelium. Methods: The study population consisted of 10 consecutive patients (mean age = 32.6±8 years) who were submitted to total thyroidectomy for DTC. All were receiving therapy with L-thyroxine to maintain TSH within the reference range. No patient enrolled presented obesity, hypertension or hyperglycemia. Patients underwent standard echocardiography-Doppler examination with evaluation of the coronary flow reserve (CFR) of the distal left anterior descending artery obtained by cold pressure test (CPT) before and 24 h after the second rhTSH injection. Results: Left ventricular morphology and systolic and diastolic function were normal in all patients. Thyroid hormones, thyroglobulin and antithyroglobulin antibodies levels did not differ before and after rhTSH. On the contrary TSH levels were higher after rhTSH administration. Blood pressure and heart rate were not affected by rhTSH. Coronary flow peak velocity at rest was similar at baseline and 24 hours post-rhTSH (22.3 ± 6 vs 23.2 ± 8.7; p = 0.66). On the contrary the post-CPT velocity (29.3 – 6.8 vs 34.4 – 10.9; p < 0.05) and the CFR were higher after rhTSH administration (1.32 – 0.2 vs. 1.53 – 0.2; p < 0.01) than at baseline in patients with DTC. Conclusion: In the present study, we demonstrated that CPT improves CFR after rhTSH administration in DTC patients receiving replacement doses of LT4. The increase of coronary blood flow after rhTSH suggests that TSH may exert a protective effect on the coronary endothelium

A real time loop-mediated isothermal amplification (RealAmp) assay for rapid detection of Pleurostoma richardsiae in declining olive plants

Pleurostoma richardsiae is associated with host trunk diseases, known to cause dieback, cankers and wilting of woody trees, and human infections. This fungus was isolated from wood tissues of declining olive trees and grapevines showing esca disease symptoms, in the Apulia region of Italy. Fungus detection has been based on morphological and molecular features, which are time-consuming to identify and require well-trained personnel. Improvement of Pl. richardsiae detection in olive was achieved through development of real time loop-mediated isothermal amplification targeting the intergenic spacer (IGS) region of the fungus. Specificity of the assay was confirmed using ten Pl. richardsiae strains and 36 other fungus strains of species usually isolated from declining olive trees. The achieved limit of detection was 7.5 × 10-2 ng μL-1 of Pl. richardsiae genomic DNA. A preliminary validation of RealAmp was also performed using material from infected olive plants artificially inoculated in a greenhouse

Endothelial-mediated coronary flow reserve in patients with mild thyroid hormone deficiency

ContextAlthough coronary flow reserve (CFR) is reduced in patients with subclinical hypothyroidism (SHypo), the endothelial response of coronary vasomotion has never been explored in this clinical setting.ObjectiveTo investigate the endothelial response of coronary flow in young and middle-aged patients with SHypo, without associated cardiovascular risk factors compared with healthy control subjects.Patients and methodsThe study population consisted of 20 women (mean age 38.4+12.1 years) with newly diagnosed, untreated and persistent SHypo due to Hashimoto's thyroiditis. A total of 15 volunteers served as controls. Age, gender, body surface area, glucose, insulin levels, heart rate, systolic, diastolic, and mean blood pressure were similar in patients and controls. Body mass index was significantly higher in SHypo patients. Total cholesterol and low-density lipoprotein cholesterol, despite not significant, tended to be higher, and high-density lipoprotein cholesterol to be lower in SHypo. Coronary blood flow velocities were recorded in patients at rest and after the cold pressor test (CPT), a stimulus that can be considered totally endothelium-dependent. CFR was calculated as the ratio of hyperemic-to-resting diastolic peak velocities.ResultsCoronary diastolic peak velocities at rest did not differ between the two groups but were significantly lower after CPT in patients with SHypo, thereby resulting in a lower CFR. The difference remained significant after adjusting resting and CPT velocities for the respective mean blood pressures. TSH was inversely correlated with CFR in the pooled population.ConclusionPatients with SHypo without associated cardiovascular risk factors have a coronary endothelial dysfunction that appears in response to a physiological stimulus (the CPT)

Relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine up to four months post administration in individuals aged 80 years or more in Italy. A retrospective matched cohort study

Several countries started a 2nd booster COVID-19 vaccination campaign targeting the elderly population, but evidence around its effectiveness is still scarce. This study aims to estimate the relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine in the population aged &gt;= 80 years in Italy, during predominant circulation of the Omicron BA.2 and BA.5 subvariants. We linked routine data from the national vaccination registry and the COVID-19 surveillance system. On each day between 11 April and 6 August 2022, we matched 1:1, according to several demographic and clinical characteristics, individuals who received the 2nd booster vaccine dose with individuals who received the 1st booster vaccine dose at least 120 days earlier. We used the Kaplan-Meier method to compare the risks of SARS-CoV-2 infection and severe COVID-19 (hospitalisation or death) between the two groups, calculating the relative vaccine effectiveness (RVE) as (1 - risk ratio)X100. Based on the analysis of 831,555 matched pairs, we found that a 2nd booster dose of mRNA vaccine, 14-118 days post administration, was moderately effective in preventing SARS-CoV-2 infection compared to a 1st booster dose administered at least 120 days earlier [14.3 %, 95 % confidence interval (CI): 2.2-20.2]. RVE decreased from 28.5 % (95 % CI: 24.7-32.1) in the time-interval 14-28 days to 7.6 % (95 % CI: -14.1 to 18.3) in the time-interval 56-118 days. However, RVE against severe COVID19 was higher (34.0 %, 95 % CI: 23.4-42.7), decreasing from 43.2 % (95 % CI: 30.6-54.9) to 27.2 % (95 % CI: 8.3-42.9) over the same time span. Although RVE against SARS-CoV-2 infection was much reduced 2-4 months after a 2nd booster dose, RVE against severe COVID-19 was about 30 %, even during prevalent circulation of the Omicron BA.5 subvariant. The cost-benefit of a 3rd booster dose for the elderly people who received the 2nd booster dose at least four months earlier should be carefully evaluated

Effectiveness of mRNA vaccines and waning of protection against SARS-CoV-2 infection and severe covid-19 during predominant circulation of the delta variant in Italy. Retrospective cohort study

Objectives: To estimate the effectiveness of mRNA vaccines against SARS-CoV-2 infection and severe covid-19 at different time after vaccination. Design: Retrospective cohort study. Setting: Italy, 27 December 2020 to 7 November 2021. Participants: 33 250 344 people aged ≥16 years who received a first dose of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine and did not have a previous diagnosis of SARS-CoV-2 infection. Main outcome measures: SARS-CoV-2 infection and severe covid-19 (admission to hospital or death). Data were divided by weekly time intervals after vaccination. Incidence rate ratios at different time intervals were estimated by multilevel negative binomial models with robust variance estimator. Sex, age group, brand of vaccine, priority risk category, and regional weekly incidence in the general population were included as covariates. Geographic region was included as a random effect. Adjusted vaccine effectiveness was calculated as (1-IRR)×100, where IRR=incidence rate ratio, with the time interval 0-14 days after the first dose of vaccine as the reference. Results: During the epidemic phase when the delta variant was the predominant strain of the SARS-CoV-2 virus, vaccine effectiveness against SARS-CoV-2 infection significantly decreased (P&lt;0.001) from 82% (95% confidence interval 80% to 84%) at 3-4 weeks after the second dose of vaccine to 33% (27% to 39%) at 27-30 weeks after the second dose. In the same time intervals, vaccine effectiveness against severe covid-19 also decreased (P&lt;0.001), although to a lesser extent, from 96% (95% to 97%) to 80% (76% to 83%). High risk people (vaccine effectiveness -6%, -28% to 12%), those aged ≥80 years (11%, -15% to 31%), and those aged 60-79 years (2%, -11% to 14%) did not seem to be protected against infection at 27-30 weeks after the second dose of vaccine. Conclusions: The results support the vaccination campaigns targeting high risk people, those aged ≥60 years, and healthcare workers to receive a booster dose of vaccine six months after the primary vaccination cycle. The results also suggest that timing the booster dose earlier than six months after the primary vaccination cycle and extending the offer of the booster dose to the wider eligible population might be warranted

The Polycomb BMI1 Protein Is Co-expressed With CD26+ in Leukemic Stem Cells of Chronic Myeloid Leukemia

The Polycomb gene BMI1 expression exerts a negative predictive impact on several hematological malignancies, such as acute and chronic myeloid leukemia (CML), myelofibrosis, and follicular lymphoma. As already demonstrated in CML, BMI1 is responsible for the resistance to the tyrosine kinase inhibitors (TKIs) in a BCR-ABL1-independent way. Even if, it is unknown where BMI1 in CML is expressed (in progenitors or more mature cells). We decided, therefore, to evaluate if and where the BMI1 protein is located, focusing mainly on the CD34+/CD38-/CD26+ CML progenitors. To begin we measured, by flow cytometry, the proportion of CD34+/CD26+ cells in 31 bone marrow samples from 20 CML patients, at diagnosis and during treatment with imatinib. After that the bone marrow blood smears were stained with antibodies anti-CD26, BCR-ABL1, and BMI1. These smears were observed by a confocal laser microscope and a 3D reconstruction was then performed. At diagnosis, CD34+/CD26+ cells median value/μL was 0.48; this number increased from diagnosis to the third month of therapy and then reduced during treatment with imatinib. The number and behavior of the CD26+ progenitors were independent from the BCR-ABL1 expression, but they summed up what previously observed about the BMI1 expression modulation. In this work we demonstrate for the first time that in CML the BMI1 protein is co-expressed with BCR-ABL1 only in the cytoplasm of the CD26+ precursors; on the contrary, in other hematological malignancies where BMI1 is commonly expressed (follicular lymphoma, essential thrombocytemia, acute myeloid leukemia), it was not co-localized with CD26 or, obviously, with BCR-ABL1. Once translated into the clinical context, if BMI1 is a marker of stemness, our results would suggest the combination of the BMI1 inhibitors with TKIs as an interesting object of research, and, probably, as a promising way to overcome resistance in CML patients

Predicting respiratory failure in patients infected by SARS-CoV-2 by admission sex-specific biomarkers

Background: Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. Methods: Plasma levels of sex hormones (testosterone and 17β-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. Results: Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. Conclusions: Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring

Impatto della vaccinazione e della pregressa diagnosi sul rischio di infezione e di malattia severa associata a SARS-CoV-2. Un’analisi dei casi diagnosticati nel mese di ottobre 2022

In Italia, l’epidemia di infezioni da SARS-CoV-2 nel corso del 2022 è stata influenzata dalla predominanza della variante Omicron, caratterizzata da alta trasmissibilità, e dalla progressiva eliminazione di quasi tutte le misure non farmacologiche di prevenzione. La combinazione di questi due elementi ha determinato una notevole circolazione virale di SARS-CoV-2 con oltre 24,5 milioni di casi da inizio epidemia. Dato l’alto numero di persone che ha superato almeno una infezione da SARS-CoV-2 e l’alta copertura vaccinale nella popolazione è necessario stimare il ruolo protettivo dell’immunità associata sia al vaccino che all’infezione pregressa nel prevenire l’infezione e la malattia severa da COVID-19. Il presente rapporto fornisce una stima del rischio di infezione e di malattia grave, per il mese di ottobre 2022, sulla base della vaccinazione e della precedente infezione. La massima protezione contro la diagnosi di infezione da SARS-CoV-2 e la malattia severa si realizza attraverso una immunità ibrida (l’effetto combinato della vaccinazione e della pregressa infezione) mentre livelli di rischio più alto si riscontrano sempre tra le persone non vaccinate e senza una precedente diagnosi di infezione. A parità di fascia di età e di pregressa infezione, si osserva una tendenza alla riduzione del rischio di malattia severa associata alla vaccinazione, in particolare se recente

Association between preoperative evaluation with lung ultrasound and outcome in frail elderly patients undergoing orthopedic surgery for hip fractures: study protocol for an Italian multicenter observational prospective study (LUSHIP)

Hip fracture is one of the most common orthopedic causes of hospital admission in frail elderly patients. Hip fracture fixation in this class of patients is considered a high-risk procedure. Preoperative physical examination, plasma natriuretic peptide levels (BNP, Pro-BNP), and cardiovascular scoring systems (ASA-PS, RCRI, NSQIP-MICA) have all been demonstrated to underestimate the risk of postoperative complications. We designed a prospective multicenter observational study to assess whether preoperative lung ultrasound examination can predict better postoperative events thanks to the additional information they provide in the form of "indirect" and "direct" cardiac and pulmonary lung ultrasound signs

A multi-parametric and multi-layer study to investigate the largest 2022 Hunga Tonga–Hunga Ha’apai eruptions

On 20 December 2021, after six quiet years, the Hunga Tonga-Hunga Ha'apai volcano erupted abruptly. Then, on 15 January 2022, the largest eruption produced a plume well registered from satellites and destroyed the volcanic cone previously formed in 2015, connecting the two islands. We applied a multi-parametric and multi-layer study to investigate all the possible pre-eruption signals and effects of this volcanic activity in the lithosphere, atmosphere, and ionosphere. We focused our attention on: (a) seismological features considering the eruption in terms of an earthquake with equivalent energy released in the lithosphere; (b) atmospheric parameters, such as skin and air temperature, outgoing longwave radiation (OLR), cloud cover, relative humidity from climatological datasets; (c) varying magnetic field and electron density observed by ground magnetometers and satellites, even if the event was in the recovery phase of an intense geomagnetic storm. We found different precursors of this unique event in the lithosphere, as well as the effects due to the propagation of acoustic gravity and pressure waves and magnetic and electromagnetic coupling in the form of signals detected by ground stations and satellite data. All these parameters and their detailed investigation confirm the lithosphere-atmosphere-ionosphere coupling (LAIC) models introduced for natural hazards such as volcano eruptions and earthquakes