Spina bifida and cardiorespiratory profile: the impact of leisure sport activities on physical fitness.

PURPOSE: The aim of the present study is to evaluate a population of young patients affected by Spina Bifida (SB) to describe their cardiorespiratory function and bone mineral density profile, analyzing any differences between people performing and those who do not perform sports activity. The study also aimed to rule out possible congenital heart disease associated with spina bifida, considering the common origin of certain cardiac structures with those found to be altered in SB patients. METHODS: Thirty-four young patients, aged between 12 and 22 years, diagnosed with spinal dysraphism (SD), have been clinically described and, in order to evaluate their physical fitness, functional capacity and bone mass, almost all of them underwent a complete cardiorespiratory assessment, including electrocardiogram (ECG), echocardiogram, Cardiopulmonary Exercise Test (CPET), body composition analysis using bioimpedance analysis (BIA) and Dual Energy X-ray Absorptiometry (DEXA), as well as the estimation of bone mineral density (BMD) with Computerized Bone Mineralometry (CBM). RESULTS: Collected data demonstrated that only 35% of the subjects practiced physical activity during the week. BMI and percentage FM values were pathological in at least 50% of the population. On cardiological investigations (ECG and echocardiogram), no significant alterations were found. In all patients who performed CPET (79.4%), pathological values of the main functional capacity parameters were revealed, especially peak oxygen consumption (VO2 peak), even when corrected for BCM or FFM estimated at BIA and DEXA, respectively. In the CBM analysis, out of 27 patients in whom the femoral T-score was evaluated, a condition of osteopenia was revealed in 40.7% of the patients (11/27) and osteoporosis in 18.5% (5/27); out of 27 patients in whom the lumbar T-score was evaluated, 37% of the patients showed osteopenia (10/27) and 29.6% osteoporosis (8/27). When the comparison between exercising and non-exercising patients was performed, the only statistically significant difference that emerged was the median lumbar T-score value, which appeared lower in the group not performing physical activity (p = 0,009). CONCLUSIONS: The extensive cardiorespiratory evaluation, including CPET, of our cohort of spina bifida patients showed altered values of the main parameters related to cardiorespiratory fitness and is the only study in the literature that analysed bone mineralization values in physically active and sedentary spina bifida patients and demonstrated a statistically significant difference. Furthermore, it is the only study to date that investigated the possible association of congenital heart diseases with SD, without demonstrating the existence of pathological conditions.

The role of coronary CT angiography in athletes.

The sudden death of a young or high-level athlete or adolescent during recreational sports is one of the events with the greatest impact on public opinion in modern society. Sudden cardiac death (SCD) is the principal medical cause of death in athletes and can be the first and last clinical presentation of underlying disease. To prevent such episodes, pre-participation screening has been introduced in many countries to guarantee cardiovascular safety during sports and has become a common target among medical sports/governing organizations. Different cardiac conditions may cause SCD, with incidence depending on definition, evaluation methods, and studied populations, and a prevalence and etiology changing according to the age of athletes, with CAD most frequent in master athletes, while coronary anomalies and non-ischemic causes prevalent in young. To detect silent underlying causes early would be of considerable clinical value. This review summarizes the pre-participation screening in athletes, the specialist agonistic suitability visit performed in Italy, the anatomical characteristics of malignant coronary anomalies, and finally, the role of coronary CT angiography in such arena. In particular, the anatomical conditions suggesting potential disqualification from sport, the post-treatment follow-up to reintegrate young athletes, the diagnostic workflow to rule-out CAD in master athletes, and their clinical management are analyzed.

Alcohol-Related Liver Disease in the Covid-19 Era: Position Paper of the Italian Society on Alcohol (SIA).

BACKGROUND: Coronavirus Disease 2019 (COVID-19), firstly reported in China last November 2019, became a global pandemic. It has been shown that periods of isolation may induce a spike in alcohol use disorder (AUD). In addition, alcohol-related liver disease (ALD) is the most common consequence of excessive alcohol consumption worldwide. Moreover, liver impairment has also been reported as a common manifestation of COVID-19. AIMS: The aim of our position paper was to consider some critical issues regarding the management of ALD in patients with AUD in the era of COVID-19. METHODS: A panel of experts of the Italian Society of Alcohology (SIA) met via "conference calls" during the lockdown period to draft the SIA's criteria for the management of ALD in patients with COVID-19 as follows: (a) liver injury in patients with ALD and COVID-19 infection; (b) toxicity to the liver of the drugs currently tested to treat COVID-19 and the pharmacological interaction between medications used to treat AUD and to treat COVID-19; (c) reorganization of the management of compensated and decompensated ALD and liver transplantation in the COVID-19 era. RESULTS AND CONCLUSIONS: The COVID-19 pandemic has rapidly carried us toward a new governance scenario of AUD and ALD which necessarily requires an in-depth review of the management of these diseases with a new safe approach (management of out-patients and in-patients following new rules of safety, telemedicine, telehealth, call meetings with clinicians, nurses, patients, and caregivers) without losing the therapeutic efficacy of multidisciplinary treatment.

Myocardial bridge evaluation towards personalized medicine: study design and preliminary results of the RIALTO registry.

Myocardial bridge (MB) is the most frequent inborn coronary artery variant in which a portion of the myocardium overlies an epicardial coronary artery segment. Although MB has long been considered a benign entity, a growing body of evidence has suggested its association with angina and adverse cardiac events. However, to date, no data on long-term prognosis are available, nor on therapies improving cardiovascular outcomes. We are currently conducting an ambispective, observational, multicentre, study in which we enrol patients with a clinical indication to undergo coronary angiography (CA) and evidence of MB, aiming to describe the incidence of symptoms and cardiovascular events at baseline and at long-term follow-up (FUP). The role of invasive full-physiology assessment in modifying the discharge therapy and eventually the perceived quality of life and the incidence of major cardiovascular events will be analysed. Basal clinical-instrumental data of eligible and consenting patients have been acquired after CA; FUP was performed 6, 12, and 24 months after the angiographic diagnosis of MB. The primary endpoint of the study is the incidence of major adverse cardiovascular events (MACE), defined as the composite of cardiac death, myocardial infarction, cardiac hospitalization, and target vessel revascularization; the secondary endpoints are the rate of patients with Seattle Angina Questionnaire (SAQ) summary score <70 and the incidence of MACE in patients undergoing invasive intracoronary assessment. Among patients undergone FUP visits, we recorded 31 MACE at 6 months (11.6%), 16 MACE at 12 months (6.5%), and 26 MACE at 24 months (13.5%). The rate of patients with SAQ <70 is 18.8% at 6 months, 20.6% at 12 months, and 21.8% at 24 months. To evaluate the prognostic role of invasive intracoronary assessment, we compared MB patients who underwent only angiographic evaluation (Angio group) to those who underwent acetylcholine (ACH) provocative test with indication to calcium-channel blockers (CCBs) at discharge (Angio + ACH + CCBs group) and those who underwent functional assessment with fractional flow reserve (FFR) with indication to beta-blockers (BBs) at discharge (Angio + FFR + BBs group). After 2 years of FUP, the rate of MACE was significantly reduced in both Angio + ACH + CCBs group (6 vs. 25%, P = 0.029) and Angio + FFR + BBs group (3 vs. 25%, P = 0.005) compared with Angio group. The preliminary results of our study showed that MB may be a cause of angina and adverse cardiac events in patients referred to CA for suspected coronary artery disease (CAD). Full-physiology assessment unmasking MB-related ischaemia mechanisms, allowed to guide the treatment, personalizing the clinical management, improving the quality of life, and cardiovascular outcomes in patients with MB.

Is extensive cardiopulmonary screening useful in athletes with previous asymptomatic or mild SARS-CoV-2 infection?

OBJECTIVE: During the COVID-19 pandemic, it is essential to understand if and how to screen SARS-CoV-2-positive athletes to safely resume training and competitions. The aim of this study is to understand which investigations are useful in a screening protocol aimed at protecting health but also avoiding inappropriate examinations. METHODS: We conducted a cohort study of a professional soccer team that is based on an extensive screening protocol for resuming training during the COVID-19 pandemic. It included personal history, antigen swabs, blood tests, spirometry, resting/stress-test ECG with oxygen saturation monitoring, echocardiogram, Holter and chest CT. We also compared the findings with prior data from the same subjects before infection and with data from SARS-CoV-2-negative players. RESULTS: None of the players had positive swab and/or anti-SARS-CoV-2 IgM class antibodies. Out of 30 players, 18 (60%) had IgG class antibodies. None had suffered severe SARS-CoV-2-related disease, 12 (66.7%) had complained of mild COVID-19-related symptoms and 6 (33.3%) were asymptomatic. None of the players we examined revealed significant cardiovascular abnormalities after clinical recovery. A mild reduction in spirometry parameters versus pre-COVID-19 values was observed in all athletes, but it was statistically significant (p<0.05) only in SARS-CoV-2-positive athletes. One SARS-CoV-2-positive player showed increased troponin I level, but extensive investigation did not show signs of myocardial damage. CONCLUSION: In this small cohort of athletes with previous asymptomatic/mild SARS-CoV-2 infection, a comprehensive screening protocol including blood tests, spirometry, resting ECG, stress-test ECG with oxygen saturation monitoring and echocardiogram did not identify relevant anomalies. While larger studies are needed, extensive cardiorespiratory and haematological screening in athletes with asymptomatic/mild SARS-CoV-2 infection appears unnecessary.

Sudden Cardiac Death in Athletes in Italy during 2019: Internet-Based Epidemiological Research.

Background and objectives: An Italian nationwide pre-participation screening approach for prevention of sudden cardiac death in athletes (SCD-A) in competitive sportspeople showed promising results but did not achieve international consensus, due to cost-effectiveness and the shortfall of a monitoring plan. From this perspective, we tried to provide an epidemiological update of SCD-A in Italy through a year-long internet-based search. Materials and Methods: One year-long Google search was performed using mandatory and non-mandatory keywords. Data were collected according to prevalent SCD-A definition and matched with sport-related figures from Italian National Institute of Statistics (ISTAT) and Italian National Olympic Committee (CONI). Results: Ninety-eight cases of SCD-A in 2019 were identified (48.0% competitive, 52.0% non-competitive athletes). Male/female ratio was 13:1. The most common sports were soccer (33.7%), athletics (15.3%) and fitness (13.3%). A conclusive diagnosis was achieved only in 37 cases (33 of cardiac origin), with the leading diagnosis being coronary artery disease in 27 and a notably higher occurrence among master athletes. Combining these findings with ISTAT and CONI data, the SCD-A incidence rate in the whole Italian sport population was found to be 0.47/100,000 persons per year (1.00/100,000 in the competitive and 0.32/100,000 in the non-competitive population). The relative risk of SCD-A is 3.1 (CI 2.1-4.7; p < 0.0001) for competitive compared to non-competitive athletes; 9.9 for male (CI 4.6-21.4; p < 0.0001) with respect to female. Conclusions: We provided an updated incidence rate of SCD-A in both competitive and non-competitive sport in Italy. A higher risk of SCD-A among competitive and male athletes was confirmed, thus corroborating the value of Italian pre-participation screening in this population.

Diagnostic Workflow in Competitive Athletes with Ventricular Arrhythmias and Suspected Concealed Cardiomyopathies.

The diagnosis of structural heart disease in athletes with ventricular arrhythmias (VAs) and an apparently normal heart can be very challenging. Several pieces of evidence demonstrate the importance of an extensive diagnostic work-up in apparently healthy young patients for the characterization of concealed cardiomyopathies. This study shows the various diagnostic levels and tools to help identify which athletes need deeper investigation in order to unmask possible underlying heart disease.

Gaining Back What Is Lost: Recovering the Sense of Smell in Mild to Moderate Patients After COVID-19.

The purpose of our cohort study was to quantify olfactory deficits in Coronavirus disease 2019 (COVID-19) patients using Sniffin' Sticks and a pre-post design to evaluate olfactory recovery. Thirty adult patients with laboratory-confirmed mild to moderate forms of COVID-19 underwent a quantitative olfactory test performed with the Sniffin' Sticks test (SST; Burghardt, Wedel, Germany), considering olfactory threshold (T), odor discrimination (D), and odor identification (I). Results were presented as a composite TDI score (range 1-48) that used to define functional anosmia (TDI ≤ 16.5), hyposmia (16.5 < TDI < 30.5), or functionally normal ability to smell (TDI ≥ 30.5). Patients also self-evaluated their olfactory function by rating their ability to smell on a visual analogue scale (Visual Analog Scale rating) and answering a validated Italian questionnaire (Hyposmia Rating Scale). Patients were tested during hospitalization and about 2 months after symptoms onset. During the hospitalization, the overall TDI score indicated that our cohort had impairments in their olfactory ability (10% was diagnosed with anosmia and more than 50% were hyposmic). Almost all patients showed a significant improvement at around 1 month following the first test and for all the parts of the SST except for odor identification. None of the subjects at 1 month was still diagnosed with anosmia. We also quantified the improvement in the TDI score based on initial diagnosis. Anosmic subjects showed a greater improvement than hyposmic and normosmic subjects. In conclusion, within a month time window and 2 months after symptoms' onset, in our cohort of patients we observed a substantial improvement in the olfactory abilities.

Clinical utility of genetic testing in the early diagnosis of Danon disease mimicking hypertrophic cardiomyopathy: a case report.

BACKGROUND: Danon disease (OMIM 300257) is an X-linked lysosomal storage disorder, characterized by hypertrophic cardiomyopathy (HCM), skeletal myopathy, variable intellectual disability, and other minor clinical features. This condition accounts for ~ 4% of HCM patients, with a more severe and early onset phenotype in males, causing sudden cardiac death (SCD) in the first three decades of life. Genetic alterations in the LAMP2 gene are the main cause of this inherited fatal condition. Up to date, more than 100 different pathogenic variants have been reported in the literature. However, the majority of cases are misdiagnosed as HCM or have a delay in the diagnosis. CASE PRESENTATION: Here, we describe a young boy with an early diagnosis of HCM. After 2 episodes of ventricular fibrillation within 2 years, genetic testing identified a novel LAMP2 pathogenic variant. Subsequently, further clinical evaluations showing muscle weakness and mild intellectual disability confirmed the diagnosis of Danon disease. CONCLUSIONS: This report highlights the role of genetic testing in the rapid diagnosis of Danon disease, underscoring the need to routinely consider the inclusion of LAMP2 gene in the genetic screening for HCM, since an early diagnosis of Danon disease in patients with a phenotype mimicking HCM is essential to plan appropriate treatment, ie cardiac transplantation.

Circulating CRP Levels Are Associated with Epicardial and Visceral Fat Depots in Women with Metabolic Syndrome Criteria.

Sexual dimorphism accounts for significant differences in adipose tissue mass and distribution. However, how the crosstalk between visceral and ectopic fat depots occurs and which are the determinants of ectopic fat expansion and dysfunction remains unknown. Here, we focused on the impact of gender in the crosstalk between visceral and epicardial fat depots and the role of adipocytokines and high-sensitivity C-reactive protein (hs-CRP). A total of 141 outward patients (both men and women) with one or more defining criteria for metabolic syndrome (MetS) were consecutively enrolled. For all patients, demographic and clinical data were collected and ultrasound assessment of visceral adipose tissue (VFth) and epicardial fat (EFth) thickness was performed. Hs-CRP and adipocytokine levels were assessed by enzyme-linked immunosorbent assay (ELISA). Men were characterized by increased VFth and EFth (p-value < 0.001 and 0.014, respectively), whereas women showed higher levels of adiponectin and leptin (p-value < 0.001 for both). However, only in women VFth and EFth significantly correlated between them (p = 0.013) and also with leptin (p < 0.001 for both) and hs-CRP (p = 0.005 and p = 0.028, respectively). Linear regression confirmed an independent association of both leptin and hs-CRP with VFth in women, also after adjustment for age and MetS (p = 0.012 and 0.007, respectively). In conclusion, men and women present differences in epicardial fat deposition and systemic inflammation. An intriguing association between visceral/epicardial fat depots and chronic low-grade inflammation also emerged. In women Although a further validation in larger studies is needed, these findings suggest a critical role of sex in stratification of obese/dysmetabolic patients.

Innovative Target for Production of Technetium-99m by Biomedical Cyclotron.

Technetium-99m (99mTc) is the most used radionuclide worldwide in nuclear medicine for diagnostic imaging procedures. 99mTc is typically extracted from portable generators containing 99Mo, which is produced normally in nuclear reactors as a fission product of highly enriched Uranium material. Due to unexpected outages or planned and unplanned reactor shutdown, significant 99mTc shortages appeared as a problem since 2008 The alternative cyclotron-based approach through the 100Mo(p,2n)99mTc reaction is considered one of the most promising routes for direct 99mTc production in order to mitigate potential 99Mo shortages. The design and manufacturing of appropriate cyclotron targets for the production of significant amounts of a radiopharmaceutical for medical use is a technological challenge. In this work, a novel solid target preparation method was developed, including sputter deposition of a dense, adherent, and non-oxidized Mo target material onto a complex backing plate. The latter included either chemically resistant sapphire or synthetic diamond brazed in vacuum conditions to copper. The target thermo-mechanical stability tests were performed under 15.6 MeV proton energy and different beam intensities, up to the maximum provided by the available GE Healthcare (Chicago, IL, USA) PET trace medical cyclotron. The targets resisted proton beam currents up to 60 µA (corresponding to a heat power density of about 1 kW/cm²) without damage or Mo deposited layer delamination. The chemical stability of the proposed backing materials was proven by gamma-spectroscopy analysis of the solution obtained after the standard dissolution procedure of irradiated targets in H2O2.

Sofosbuvir and ribavirin for genotype 2 HCV infected patients with cirrhosis: A real life experience.

BACKGROUND & AIMS: Sofosbuvir (SOF) and weight-based ribarivin (RBV) represented until recently the standard of care in hepatitis C virus (HCV) genotype (GT)2 patients. In registration studies 12-16weeks duration were associated with a 90% sustained virological response at 12weeks (SVR12). Real life cohorts showed lower SVR12 rates. METHODS: SVR12 rates attained in an Italian real life cohort and possible benefits of a duration extended up to 20weeks was investigated in HCV GT2 patients with cirrhosis. The role of 2k/1b chimeras as potential predictor of treatment failure was also analysed. RESULTS: Overall, 291 HCV GT2 infected patients with bridging fibrosis or cirrhosis were evaluated. Median age was 68years (18-87); 163 were treatment naïve. Of 168 cirrhotic patients, 149 had Child-Pugh score A and 19 B, 50 platelets count <100,000/mm3 and 62 albumin <3.5g/dl. SVR12 were 95.53% overall, with 99.15% in non-cirrhotic patients and 93.06% in cirrhotic patients. In patients who completed treatment, SVR rates for cirrhotic patients resulted in 94.51%, and 94.94% after 16 or 20weeks respectively. Predictors of SVR were low platelet count and esophageal varices (OR 7.2; 95% CI 1.67-31.25; p=0.0022 and OR 0.1; 95% CI 0.01-0.72; p=0.0079, respectively). Anemia was mild in 12.4%, moderate in 3.4%, and severe in 2.4% of cases. Anemia was slightly more frequent among longer duration but not associated with treatment discontinuations. No 2k/1b strains or genotypes different from those at baseline were identified at relapse. CONCLUSIONS: In GT2 cirrhotic patients, SOF/RBV for 16 or 20weeks is associated with real life SVR12 rates of 95%. LAY SUMMARY: A duration of treatment of 16-20weeks was recommended for treatment of HCV GT2 patients using the combination of sofosbuvir and ribavirin. Real life experiences, where patients received 12weeks of treatment regardless of the severity of liver disease, suggested that response rates are lower than expected, in particular in patients with liver cirrhosis. A misleading genotyping of a 2k/1b strain as GT2 was also hypothesized as a further explanation for less effectiveness. We demonstrated that using the recommended extended duration in patients with more severe disease 95% of patients with severe liver disease including cirrhosis can be cured and that 2k/1b strain plays only a secondary role in specific countries like Germany. Although this combination has been recently replaced by sofosbuvir and velpatasvir fixed dose combination as the standard of care for treating HCV GT2 patients, our findings may inform physicians from countries where the new regimen is not yet available.

Risperidone and Cardiometabolic Risk in Children and Adolescents: Clinical and Instrumental Issues.

PURPOSE/BACKGROUND: Although second-generation antipsychotics are used to treat and manage symptoms for several psychiatric disorders, data about their adverse effects in developmental age are limited. The aim of this prospective observational study was to verify the cardiovascular and metabolic risk in a sample of antipsychotic-naive children/adolescent patients starting risperidone therapy. METHODS: Twenty-two patients, younger than 18 years, were recruited. The assessment included anthropometric data, cardiovascular parameters, blood tests, and ultrasonographic abdominal study. RESULTS: After an average follow-up period of 7.6 months, statistically significant increases in mean values of waist circumference, body mass index (BMI), BMI percentile, BMI z score, total cholesterol, and prolactin were found. Other cardiometabolic parameters showed an upward trend in time. Subjects in pubertal/postpubertal stage and female patients were more susceptible to developing cardiometabolic changes. Moreover, significant correlations between changes in anthropometric and several metabolic parameters were found. A tendency to change in constitution of the liver parenchyma and distribution of the abdominal fat mass with ultrasonographic abdominal study was also evident. CONCLUSIONS: In our sample, several metabolic parameters showed a sensitivity to risperidone treatment. Because most of these parameters are age dependent, metabolic syndrome criteria used for adults were inappropriate in children and adolescents. Periodic clinical and instrumental evaluations and guidelines for monitoring of any metabolic, laboratory, and instrumental complications are necessary in the perspective of even long-time second-generation antipsychotics treatment in children and adolescents.

High dosage of a fixed combination oxycodone/naloxone prolonged release: efficacy and tolerability in patients with chronic cancer pain.

PURPOSE: Opioids are associated with side effects in the treatment of moderate-to-severe chronic cancer pain. Oral combination of opioid agonist-antagonist oxycodone-naloxone (OXN-PR) attenuates gastrointestinal side effects; however, evidence on high-dose OXN-PR treatment is scant. This study evaluates the efficacy and tolerability of high-dose OXN-PR in chronic cancer pain. PATIENTS AND METHODS: This was a multicenter, prospective 60-day observation on consecutive cancer patients with uncontrolled moderate-severe chronic pain or intolerant to other analgesics, who were switched at entry visit (T0) to OXN-PR ≥80 mg daily. Patients were reassessed 14, 30, 45, and 60 days later (T60). Primary endpoint of the study was analgesic response rate (decrease ≥30% of pain intensity from baseline, measured on a 0-10 numerical rating scale, NRS) after 30 days on OXN-PR. Additional endpoints assessed at every visit were the impact of pain on quality of life (QoL), breakthrough cancer pain (BTCP) episodes, opioid dosage escalation index, bowel dysfunction, safety, and other side effects. RESULTS: One hundred nineteen patients were included (age 64 ± 12, metastatic disease in 91.6%); 101 of them (84.9%) completed the 60-day observation. At T0, the majority had severe pain (NRS ≥7 in 79.8%; neuropathic features in 83.2%). Response rate at 30-day visit was 79.8% (n = 95). OXN-PR resulted in a significant reduction in pain over time (T0: 7.4 ± 1.3; T60: 3.3 ± 1.8; p < 0.001), and the number of daily (BTCP) declined (3.9 ± 2.2 vs. 2.0 ± 0.6, p < 0.001). Daily dosage of OXN-PR slightly increased (T0: 81.3 ± 6.0; T60: 93.6 ± 34.0; p < 0.001). The impact of pain on QoL abated (p < 0.0001), and bowel function improved overtime (p < 0.001). After the switch to OXN-PR, the number of patients complaining for side effects decreased overall (p < 0.0001); laxatives and antiemetic use also declined significantly. CONCLUSIONS: OXN-PR was highly effective and well tolerated even at high doses in cancer patients with chronic pain. The agonist-antagonist combination rapidly alleviated pain and its impact on life style, reducing the number of BTCP and improving opioid side effects.

Bile Acids and Cancer: Direct and Environmental-Dependent Effects.

Bile acids (BAs) regulate the absorption of fat-soluble vitamins, cholesterol and lipids but have also a key role as singalling molecules and in the modulation of epithelial cell proliferation, gene expression and metabolism. These homeostatic pathways, when disrupted, are able to promote local inflammation, systemic metabolic disorders and, ultimately, cancer. The effect of hydrophobic BAs, in particular, can be linked with cancer in several digestive (mainly oesophagus, stomach, liver, pancreas, biliary tract, colon) and extra-digestive organs (i.e. prostate, breast) through a complex series of mechanisms including direct oxidative stress with DNA damage, apoptosis, epigenetic factors regulating gene expression, reduced/increased expression of nuclear receptors (mainly farnesoid X receptor, FXR) and altered composition of gut microbiota, also acting as a common interface between environmental factors (including diet, lifestyle, exposure to toxics) and the molecular events promoting cancerogenesis. Primary prevention strategies (i.e. changes in dietary habits and lifestyle, reduced exposure to environmental toxics) mainly able to modulate gut microbiota and the epigenome, and the therapeutic use of hydrophilic BAs to counterbalance the negative effects of the more hydrophobic BAs might be, in the near future, part of useful tools for cancer prevention and management.

QTc Interval in Adolescents and Young Athletes: Influence of Correction Formulas.

A QTc interval at the upper limits in young athletes can be challenging. Regardless of factors able to influence it (age, electrolytes, etc.), several authors underlined that rate correction formulas can often underestimate/overestimate it. Our objective was to identify the most reliable formula and relative upper normal limit of QTc for this population. The rest ECG of 701 healthy elite male athletes was analyzed. QTc was calculated with 4 formulas (Bazett, Fridericia, Framingham, Hodges). Correlation/regression analysis of QTc vs. heart rate and upper limits were calculated and compared considering different age groups. Abnormal ECGs were compared considering different upper limits. Correlation between QTc and heart rate was highly significant using Bazett's and Framingham's formulas, lower using Hodges' formula, and not significant using Fridericia's formula. Except for Framingham's, the number of abnormal ECGs was identical considering an upper limit of 480 msec, and significantly different for lower limits. Upper limits were: Bazett 469 msec, Fridericia 451 msec, Framingham 458 msec, and Hodges 461 msec. Except for Framingham's, no difference among other formulas in individuating abnormal ECGs for QTc≥480 msec was found. QTc obtained with the Bazett's formula appears highly dependent on heart rate. This, especially in the grey zone (440-480 msec), can lead to overtesting. Framingham's formula shows similar limits. Hodges' formula offers uncertain reliability. Fridericia's formula seems the most reliable.

The p66Shc protein controls redox signaling and oxidation-dependent DNA damage in human liver cells.

The p66Shc protein mediates oxidative stress-related injury in multiple tissues. Steatohepatitis is characterized by enhanced oxidative stress-mediated cell damage. The role of p66Shc in redox signaling was investigated in human liver cells and alcoholic steatohepatitis. HepG2 cells with overexpression of wild-type or mutant p66Shc, with Ser36 replacement by Ala, were obtained through infection with recombinant adenoviruses. Reactive oxygen species and oxidation-dependent DNA damage were assessed by measuring dihydroethidium oxidation and 8-hydroxy-2'-deoxyguanosine accumulation into DNA, respectively. mRNA and protein levels of signaling intermediates were evaluated in HepG2 cells and liver biopsies from control and alcoholic steatohepatitis subjects. Exposure to H2O2 increased reactive oxygen species and phosphorylation of p66Shc on Ser36 in HepG2 cells. Overexpression of p66Shc promoted reactive oxygen species synthesis and oxidation-dependent DNA damage, which were further enhanced by H2O2. p66Shc activation also resulted in increased Erk-1/2, Akt, and FoxO3a phosphorylation. Blocking of Erk-1/2 activation inhibited p66Shc phosphorylation on Ser36. Increased p66Shc expression was associated with reduced mRNA levels of antioxidant molecules, such as NF-E2-related factor 2 and its target genes. In contrast, overexpression of the phosphorylation defective p66Shc Ala36 mutant inhibited p66Shc signaling, enhanced antioxidant genes, and suppressed reactive oxygen species and oxidation-dependent DNA damage. Increased p66Shc protein levels and Akt phosphorylation were observed in liver biopsies from alcoholic steatohepatitis compared with control subjects. In human alcoholic steatohepatitis, increased hepatocyte p66Shc protein levels may enhance susceptibility to DNA damage by oxidative stress by promoting reactive oxygen species synthesis and repressing antioxidant pathways.