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Background: The prognostic impact of electrolyte disorders in hospitalized COVID-19 patients is unclear. Methods: The study included all adult patients hospitalized for COVID-19 in four hospitals in Northern Italy between January 2020 and May 2021 with at least one serum potassium and sodium measurement performed within 3 days since admission. Primary outcome was in-hospital death; secondary outcome was Intensive Care Unit (ICU) admission. A cause-specific Cox proportional-hazards regression model was used for investigating the association between potassium and sodium (as either categorical or continuous variables) and mortality or admission to ICU. Results: Analyses included 3,418 adult hospitalized COVID-19 patients. At multivariable analysis, both hyperkalemia (Hazard Ratio, [HR] 1.833, 95% Confidence Interval [CI] 1.371–2.450) and sK above the median (K 5.1 vs 4.1 mmol/L: HR 1.523, 95% CI 1.295–1.798), and hypernatremia (HR 2.313, 95%CI 1.772–3.018) and sNa above the median (Na 149 vs 139 mmol/L: HR 1.442, 95% CI 1.234–1.686), were associated with in-hospital death, whereas hypokalemia and hyponatremia were not. Hyponatremia was associated with increased hazard of ICU admission (HR 1.884, 95%CI 1.389–2.556). Conclusions: Electrolyte disorders detected at hospital admission may allow early identification of COVID-19 patients at increased risk of adverse outcomes.

Background: Osteoporosis is a common concern in the elderly that leads to fragile bones. Calcium supplementation plays a crucial role in improving bone health, reducing fracture risk, and supporting overall skeletal strength in this vulnerable population. However, there is conflicting evidence on the safety of calcium supplements in elderly individuals. Aim: The aim of this study was to evaluate the adherence, safety and tolerability of calcium citrate supplementation in elderly osteopenic subjects. Methods: In this non-interventional, prospective, multicenter study, subjects received daily 500 mg calcium citrate supplementation for up to one year. Adherence was calculated based on compliance and persistence. Safety was assessed through adverse reactions (ARs), deaths, and clinical laboratory evaluations. Results: A total of 268 Caucasian subjects (91.4% female, mean age 70 ± 4.5 years) participated in the study. Mean adherence to treatment was 76.6 ± 29.5% and half of subjects had an adherence of 91% and ~ 33% of participants achieved complete (100%) adherence. ARs were reported by nine (3.9%) subjects, primarily gastrointestinal disorders, with no serious ARs. The frequency of all adverse events (including ARs) was significantly higher in subjects with adherence of < 80% (41.6%; 32/77) vs. those with adherence ≥ 80% (11%; 16/145, p < 0.0001). Both systolic and diastolic blood pressure decreased from baseline to follow-up visit (change of -2.8 ± 13.9 mmHg, p = 0.0102 and -2.1 ± 10.4 mmHg, p = 0.0116, respectively). Conclusion: This study demonstrated favorable adherence to calcium citrate supplementation in elderly osteopenic subjects. The occurrence of ARs, though generally mild, were associated with lower adherence to calcium supplementation.

Deucrictibant is a selective, orally-administered bradykinin B2 receptor antagonist under development for on-demand and prophylactic treatment of hereditary angioedema (HAE) attacks.

Issues related to the continuity of interest requirement for tax-free corporate reorganizations are examined, focusing on the latest final regulations issued by the IRS and Treasury Dept on Aug 30, 2000. Topics include an overview of the requirement, redemptions and extraordinary distributions, a comparison of the temporary and final regulations, implications of a prereorganization redemption by the target company, and use of IRC section 356 to determine how continuity of interest is affected by the redemption or distribution.

Issues surrounding the tax treatment of transaction costs for business expansion are examined, focusing on the August 2000 decision by the US 8th Circuit Court of Appeals in Wells Fargo & Co. v. Commissioner. Topics include the court's partial reversal of Tax Court's 1999 decision in Norwest Corp v. Commissioner, the historical importance of the US Supreme Court's 1992 decision in INDOPCO v. Commissioner, the taxpayers' victory in the Wells Fargo decision, history of investigatory costs, and the distinction between business expansion and new trade or business.

Issues concerning the taxation of transaction costs related to the acquisition of assets are examined, focusing on the US 8th Circuit Court of Appeals 2000 decision in Wells Fargo & Co. v. Commissioner and how it relates to the Tax Court's 1999 decision in Norwest Corp. v. Commissioner. Topics include history if investigatory costs, implications of the 8th Circuit's reversal of Norwest, and unresolved issues following the Wells Fargo decision.

Aim: Healthy lifestyle behaviors and a good adherence to pharmacological treatments are important predictors of lower recurrence rates and better overall outcomes among patients with an established acute coronary syndrome (ACS). The present study sought to investigate the longitudinal trajectories of these behaviors years after the onset of an ACS. Subject and methods: We recruited a sample of 275 newly diagnosed consecutive patients at their first ACS event (mean age: 57.1 ± 7.87 years; 84% males) admitted to a cardiac rehabilitation program from three large public hospitals in Northern Italy. Patients completed a battery of sociodemographic questionnaires, which evaluated healthy lifestyles (smoking status, alcohol intake, diet, and physical activity) and adherence to pharmacological treatments, at five time-points (pre-event, 6-, 12-, 24-, and 36-month follow-ups). Longitudinal trajectories were examined through hierarchical (generalized) linear models, controlling for several demographic and clinical variables. Results: We found significant changes in all healthy lifestyles from pre-event to the 6-month follow-up, suggesting the adoption of healthier behaviors soon after the cardiac event. However, from the 6-month up to the 3-year follow-up, patients experienced small but significant declines in their self-reported levels of healthy dietary behaviors and physical activity. Further, we found that the odds of being at medium risk of non-adherence to the pharmacological treatments significantly increased over the course of 3 years. Conclusion: Given the negative long-term trajectories in specific lifestyles and adherence to pharmacological treatments, cardiac rehabilitation programs are suggested to provide repeated psychological interventions aimed at fostering patients’ capabilities to self-regulate their habitual behaviors.

Background: Hyperuricemia is commonly observed in patients with chronic kidney disease (CKD). However, a better understanding of the relationship among uric acid (UA) values, glomerular filtration rate (GFR) and albuminuria may shed light on the mechanisms underlying the excess of cardiovascular mortality associated with both chronic kidney disease and hyperuricemia and lead to better risk stratification. Our main goal was to study the relationships between serum uric acid and kidney disease measures (namely estimated GFR [eGFR] and albuminuria) in a large cohort of individuals at cardiovascular risk from the URic acid Right for heArt Health (URRAH) Project database. Methods: Clinical data of 26,971 individuals were analyzed. Factors associated with the presence of hyperuricemia defined on the basis of previously determined URRAH cutoffs for cardiovascular and all-cause mortality were evaluated through multivariate analysis. Chronic kidney disease was defined as eGFR < 60 ml/min per 1.73 m2and/or abnormal urinary albumin excretion diagnosed as: (i) microalbuminuria if urinary albumin concentration was > 30 and ≤ 300 mg/L, or if urinary albumin-to-creatinine ratio (ACR) was > 3.4 mg/mmol and ≤ 34 mg/mmol; (ii) macroalbuminuria if urinary albumin concentration was > 300 mg/L, or if ACR was > 34 mg/mmol. Results: Mean age was 58 ± 15 years (51% males, 62% with hypertension and 12% with diabetes), mean eGFR was 81 ml/min per 1.73m22with a prevalence of eGFR < 60 and micro- or macroalbuminuria of 16, 15 and 4%, respectively. Serum uric acid showed a trend towards higher values along with decreasing renal function. Both the prevalence of gout and the frequency of allopurinol use increased significantly with the reduction of eGFR and the increase in albuminuria. Hyperuricemia was independently related to male gender, eGFR strata, and signs of insulin resistance such as body mass index (BMI) and triglycerides. Conclusions: The lower the eGFR the higher the prevalence of hyperuricemia and gout. In subjects with eGFR < 60 ml/min the occurrence of hyperuricemia is about 10 times higher than in those with eGFR > 90 ml/min. The percentage of individuals treated with allopurinol was below 2% when GFR was above 60 ml/min, it increased to 20% in the presence of CKD 3b and rose further to 35% in individuals with macroalbuminuria. Graphic abstract:

Background: Robust data on case fatality rate (CFR) among inpatients with COVID-19 are still lacking, and the role of patient characteristics in in-hospital deaths remains under-investigated. This study quantified the overall CFR and described its trend in a cohort of hospitalized patients with SARS-CoV-2 in Italy. Admission to ICU, death, or discharge were the secondary outcomes. Methods: This retrospective study is based on administrative health data and electronic case records of inpatients consecutively admitted to Niguarda Hospital between 21 February and 8 November 2020. Results: An overall CFR of 18% was observed. CFR was significantly reduced during the second wave of contagion (1 June to 30 September, 16%) compared with the first wave (21 February to 31 May, 21% p= 0.015). Such reduction was mainly observed among male inpatients between 40 and 80 years with limited comorbidities. Admission to ICU was associated with a high risk of mortality in both waves. The incidence of severe disease and the need for ICU admission were lower in the second wave. Conclusion: CFR in SARS-CoV-2 inpatients was demonstrated to decrease over time. This reduction may partly reflect the changes in hospital strategy and clinical practice. The reasons for this improvement should be further investigated to plan an exit strategy in case of future outbreaks. Key messages: What is already known on this topic

In this study, Dolce et al. investigated connections between Ctf4-mediated processes involved in drug resistance, and conducted a suppressor screen of ctf4Δ sensitivity to the methylating agent MMS. Their findings demonstrate a chromatin-based drug resistance mechanism in which defects in parental histone transfer after replication fork passage impair error-free recombination bypass and lead to up-regulation of TLS-mediated mutagenesis and drug resistance.

The baroreceptor-heart rate reflex in human is impaired 2 days after a myocardial infarction but it improves 10 days after the acute coronary event. This study investigated whether (1) the baroreceptor-heart rate reflex improvement takes the reflex back to normal, and (2) the cardiopulmonary reflex is affected by myocardial infarction. In subjects studied 8 to 11 days after a transmural anterior or inferior myocardial infarction the baroreceptor-heart rate reflex sensitivity (slope of the linear regression between negative neck chamber pressures and lengthenings in RR interval) was similar to that seen in control subjects (-6.2 [+ or -] 0.8 vs -6.0 [+ or -] 0.6 ms/mm Hg, mean [+ or -] SEM) and did not change when reassessed 10 days later. In contrast, the cardiopulmonary reflex sensitivity (changes in forearm vascular resistance induced by changing central venous pressure through non-hypotensive lower body suction and leg raising) was markedly less in subjects studied 8 to 11 days after myocardial infarction than in control subjects; the reduction amounted to 58.1 [+ or -] 8% (p

In professional athletes with marked cardiac hypertrophy, reflex influences originating from cardiopulmonary receptors are impaired. To determine whether the reflex is restored after termination of physical training and regression of cardiac hypertrophy 8 former athletes (age 31 [+ or -] 6 years, mean [+ or -] SD) who stopped agonistic activity for 5 [+ or -] 1 years were compared with 15 sedentary subjects (27 [+ or -] 7 years) and 19 active professional athletes (22 [+ or -] years). Cardiopulmonary receptor stimulation and deactivation were obtained by increasing and reducing left ventricular end-diastolic diameter (echocardiography) through leg raising and nonhypotensive lower body negative pressure, respectively. Left ventricular mass index (echocardiography) was markedly and significantly (p

OBJECTIVE--To evaluate the prevalence of β-cell autoimmunity and the usefulness of a type 1 diabetes screening in patients with celiac disease. RESEARCH DESIGN AND METHODS--We measured GAD antibodies (GADAs), insulinoma-associated [...]

AbstractThis article examines the limits that academics from peripheral countries might encounter while trying to influence the decision-making process inside an international organization. Although there are different mechanisms whereby academia might influence non-academic debates, we highlight here the use of policy papers, in order to examine and discuss the non-textual barriers which might be faced by those academics. After an analysis of primary sources this article presents some pragmatic limits in the use of policy papers and discusses the consequences of this condition for the legitimation of international organizations. As such, relevant international organizations still seem to be unresponsive to some initiatives in particular: closed to the spontaneous participation of academia; and not willing to call for contributions from academic communities. This is particularly relevant for contributions from peripheral academia and other non-state actors, who lack the capability to disturb the traditional ideational power exercised by core (Western) countries and by state-centric ideology in current international law.

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Substrate analysis of the left atrium in patients undergoing atrial fibrillation ablation has limitations when performed by means of simple bipolar acquisition. To evaluate the incidence of low‐voltage zones (LVZs) through maps constructed by means of various catheters: multipolar (MC), omnipolar (OC), and circular catheters (CMCs) with the 3D electro‐anatomical systems (3d‐S) CARTO3 and EnSite Precision. To assess LVZs, we acquired maps by means of CMC and MC in the voltage range 0.05‐0.5 mV in 70 consecutive patients in sinus rhythm. In the case of OC only, we made an intra‐patient comparison of bipolar maps constructed by means of the along and across, and HD‐Wave configurations of the EnSite 3d‐S in the ranges of 0.05‐0.5 and 0.5‐1.0 mV. On the basis of this comparison, we chose the range that best identified LVZs as a set of different colors (SDC) compatible with patchy fibrosis (qualitative analysis). Subsequently, we detected the voltage values corresponding to purple and gray points, close to SDC, and the value inside corresponding to blue, green, and red colors, and we evaluated the color change in other voltage ranges. Finally, we performed a quantitative analysis of LVZs by applying the qualitative characteristics described above. On the basis of our settings, for OC, the optimal range identifying LVZs was 0.3‐0.6 mV. OC revealed smaller LVZs than MC (P< .05 or P< .001), except in the lateral wall. No significant differences were observed between CMCs. In our experience, OC does not present the limits of bipolar HD maps, though further studies are needed in order to confirm that 0.3‐0.6 mV is the optimal voltage range within which to identify LVZs. This project aims to evaluate the incidence of low voltages through maps constructed by means of various catheters: multipolar (MC), omnipolar (OC), and circular catheters (CMCs) with the 3D electro‐anatomical systems (3d‐S) using an optimized voltage range (0.3‐0.6 mV) to identify better LVZs.

The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18–95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7 ± 61.8 months. A total of 14,588 subjects were included in the analysis. A prognostic cut-off value of SUA able to discriminate combined CBV events (>4.79 mg/dL or >284.91 µmol/L) was identified by means of receiver operating characteristic curve in the whole database. Multivariate Cox regression analysis adjusted for confounders (age, sex, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, body mass index, low-density lipoprotein cholesterol, and use of diuretics) identified an independent association between SUA and combined CBV events in the whole database (HR 1.249, 95% confidence interval, 1.041–1.497, p= 0.016). The results of the present study confirm that SUA is an independent risk marker for CBV events after adjusting for potential confounding variables, including arterial hypertension, and demonstrate that >4.79 mg/dL is a valid prognostic cut-off value.

Purpose of our study was to assess the prevalence of hypertension mediated organ damage (HMOD) in healthy subjects with high-normal Blood Pressure (BP) comparing them with subjects with BP values that are considered normal (<130/85 mmHg) or indicative of hypertension (≥140/90 mmHg). Seven hundred fifty-five otherwise healthy subjects were included. HMOD was evaluated as pulse wave velocity (PWV), left ventricular mass index (LVMI), and carotid intima-media thickness (IMT) and plaque. When subjects were classified according to BP levels we found that the high-normal BP group showed intermediate values of PWV and higher values of IMT. This corresponds to intermediate prevalence of arterial stiffness, while there were no differences for increased IMT or carotid plaque. No subjects showed left ventricular hypertrophy. At multivariable analysis, the odds of having arterial stiffness or carotid HMOD in the high-normal group resulted not different to the normal group. In conclusion, in our otherwise healthy population, high-normal BP values were not related to aortic, carotid or cardiac HMOD.

Epigenetic plasticity is a pivotal factor that drives metastasis. Here, we show that the promoter of the gene that encodes the ubiquitin ligase subunit FBXL7 is hypermethylated in advanced prostate and pancreatic cancers, correlating with decreased FBXL7mRNA and protein levels. Low FBXL7mRNA levels are predictive of poor survival in patients with pancreatic and prostatic cancers. FBXL7 mediates the ubiquitylation and proteasomal degradation of active c-SRC after its phosphorylation at Ser?104. The DNA-demethylating agent decitabine recovers FBXL7 expression and limits epithelial-to-mesenchymal transition and cell invasion in a c-SRC-dependent manner. In vivo, FBXL7-depleted cancer cells form tumours with a high metastatic burden. Silencing of c-SRC or treatment with the c-SRC inhibitor dasatinib together with FBXL7 depletion prevents metastases. Furthermore, decitabine reduces metastases derived from prostate and pancreatic cancer cells in a FBXL7-dependent manner. Collectively, this research implicates FBXL7as a metastasis-suppressor gene and suggests therapeutic strategies to counteract metastatic dissemination of pancreatic and prostatic cancer cells.