Elevated Blood Homocysteine and Risk of Alzheimer's Dementia: An Updated Systematic Review and Meta-Analysis Based on Prospective Studies.

OBJECTIVE: To investigate whether high serum homocysteine (Hcy) levels is associated with the risk of developing Alzheimer's disease (AD) by performing a meta-analysis based on updated published data. METHODS: We conducted a comprehensive research using Medline (Pubmed), Scopus, Web of Science and EMBASE databases to identify all prospective studies published any time to July 7, 2020 evaluating the association between elevated Hcy levels and AD risk. RESULTS: From an initial screening of 269 published papers, 9 prospective investigations conducted on a total of 7474 subjects with mean follow-up of 9.5 years (range: 3.7-10) were included in the meta-analysis. Eight seventy-five of these subjects converted to AD. Hcy was significantly higher in these individuals (HRadjusted:1.48, 95% CI:1.23-1.76, I2=65.6%, p<0.0001) compared with who did not convert to AD. There was a significant publication bias (Egger's test, t=6.39, p=0.0003) and this was overcome by the trim and fill method, which allowed to calculate a bias-corrected imputed risk estimate of HRadjusted:1.20, 95% CI:1.01-1.44, Q value=41.92. CONCLUSIONS: The present meta-analysis found that having higher Hcy increases the risk of AD in the elderly and this finding is consistent with the widely suggested role of this non-proteinogenic α-amino acid in AD neurodegeneration.

Ensiled biomass of Solaris tobacco variety used as forage: chemical characteristics and effects on growth, welfare, and follow-up of Holstein heifers.

This study examined the use of an innovative tobacco variety, Nicotiana tabacum L., cv. Solaris, as forage. The whole plant biomass was ensiled, and the composition of SiloSolaris from bunker-silo and mini-silos was investigated. The effects of dietary inclusion of SiloSolaris on the growth, welfare, and nutritional profile of sixteen Holstein heifers, divided into two groups (n = 8), SiloSolaris (SS) and Control (CTR), were investigated. Heifers were group-fed diets with a 70:30 forage to concentrate ratio (on a DM basis). Both groups received 16.24 kg DM of concentrate mixture daily, including corn meal, wheat middlings and soybean meal. The CTR group was fed 39.43 kg DM of hay daily, and the SS group received 23.00 kg DM of the same hay and 12.69 kg DM SiloSolaris blended with the concentrate mixture. The feeding trial lasted eighty-one days with a thirty-six day adaptation phase. Data on forty-five days of diet administration are reported. At the end of the feeding trial, the plasma constituents of the heifers were studied. Moreover, heifers were monitored during a follow-up period, lasting up to 1 year after calving, for age at first insemination, age at first calving and daily milk yield. The SiloSolaris chemical composition showed an average DM content of 24.1 (±0.65) g/100 g. During ensiling, a decrease in CP and an increase in ammonia nitrogen contents were observed. The lactic acid content was variable (9.00 ± 2.66 g/100 g DM), while the acetic acid concentration was stable (4.27 ± 0.21 g/100 g DM). No butyric acid was detected in SiloSolaris, whose ammonia nitrogen content accounted for 15.7 (±1.86)% of the total nitrogen on average, and the mean pH value was 5.02 (±0.08). The SiloSolaris diet did not affect heifer growth performance. No differences were detected for body condition, fecal consistency, or locomotion scores. All the investigated plasma constituents were within or very close to the ranges reported for heifers; however, significant differences between the experimental groups were observed for triglycerides, cholesterol, albumin, and magnesium. The follow-up results did not differ between the experimental groups. These initial findings suggest that Nicotiana tabacum cv. Solaris is a promising ensiled forage for growing heifers that deserve to be further investigated.

Dyslipidaemia and mortality in COVID-19 patients: a meta-analysis.

BACKGROUND: The prevalence and prognostic implications of pre-existing dyslipidaemia in patients infected by the SARS-CoV-2 remain unclear. AIM: To assess the prevalence and mortality risk in COVID-19 patients with pre-existing dyslipidaemia. DESIGN: Systematic review and meta-analysis. METHODS: Preferred reporting items for systematic reviews and meta-analyses guidelines were followed in abstracting data and assessing validity. We searched MEDLINE and Scopus to locate all the articles published up to 31 January 2021, reporting data on dyslipidaemia among COVID-19 survivors and non-survivors. The pooled prevalence of dyslipidaemia was calculated using a random-effects model and presenting the related 95% confidence interval (CI), while the mortality risk was estimated using the Mantel-Haenszel random-effect models with odds ratio (OR) and related 95% CI. Statistical heterogeneity was measured using the Higgins I2 statistic. RESULTS: Of about 18 studies, enrolling 74 132 COVID-19 patients (mean age 70.6 years), met the inclusion criteria and were included in the final analysis. The pooled prevalence of dyslipidaemia was 17.5% of cases (95% CI: 12.3-24.3%, P < 0.0001), with high heterogeneity (I2 = 98.7%). Pre-existing dyslipidaemia was significantly associated with higher risk of short-term death (OR: 1.69, 95% CI: 1.19-2.41, P = 0.003), with high heterogeneity (I2 = 88.7%). Due to publication bias, according to the Trim-and-Fill method, the corrected random-effect ORs resulted 1.61, 95% CI 1.13-2.28, P < 0.0001 (one studies trimmed). CONCLUSION: Dyslipidaemia represents a major comorbidity in about 18% of COVID-19 patients but it is associated with a 60% increase of short-term mortality risk.

The risk of thrombosis after acute-COVID-19 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has been associated with coagulation dysfunction which predisposes patients to an increased risk of both venous and arterial thromboembolism, increasing the short-term morbidity and mortality. Current data evidenced that the rate of post-discharge thrombotic events in COVID-19 patients is lower compared to that observed during hospitalization. Rather than 'true thrombotic events', these complications seem more probably 'immunothrombosis' consequent to the recent infection. Unfortunately, the absence of data from randomized controlled trials, large prospective cohorts and ambulatory COVID-19 patients, left unresolved the question regarding the need of post-discharge thromboprophylaxis due to the absence of strong-level recommendations.

CRISP: A compact RF ion source prototype for emittance scanner testing.

A movable Allison type emittance scanner is being developed to characterize the phase-space distribution of the beamlets of spectral phase interferometry for direct electric-field reconstruction, the prototype RF negative ion source of the ITER heating neutral beam injector. To test the electronics and verify the capability of the device to resolve nearby beamlets, a compact RF ion source prototype has been set up, capable of accelerating 1 mA of helium ions up to a voltage of 2 kV. A commercial 100 W RF generator creates a plasma inside a Pyrex tube, with a density between 1015 and 1016 m-3 and an electron temperature up to 15 eV. Three multi-aperture grids in accel-decel configuration extract and accelerate the ions, which are measured with a Faraday cup. We present in this paper the characterization of the ion source and its first operation, showing that it is suitable for the commissioning of the Allison scanner.

Rectal advancement flap plus adipose lipofilling (RAFAL) for the treatment of rectourethral fistulas after radical prostatectomy.

BACKGROUND: Rectourethral fistula (RUF) is a rare but significant complication after radical prostatectomy. Many different approaches have been used, but none of them has become the standard of care. METHODS: We present our series of seven patients treated with a transanal rectal advancement flap plus the injection of mesenchymal stem cells, to facilitate the healing of the fistula. Mesenchymal cells were obtained by a new mechanical device known as LIPOGEMS®. We called this technique RAFAL (rectal advancement flap plus adipose lipofilling). In all patients the RUF was a complication of laparoscopic radical prostatectomy. Fistula size ranged from 0.3 to 0.5 cm (median 0.4 cm). RESULTS: After a median follow-up of 53 months (range 6-163 months), 2 out of 7 patients experienced RUF recurrence. In both cases recurrence was successfully treated by the York-Mason technique in one case and by redo RAFAL in the other. Success rate of RAFAL was 71% (5 of 7). The total success rate of primary RAFAL and redo- RAFAL was 85.7% (6 of 7). No short- or long-term complications were seen. CONCLUSIONS: In our patient population this new procedure was safe and effective.

Very long-term outcomes of transcatheter secundum atrial septal defect closure using intracardiac echocardiography without balloon sizing.

AIM: To assess the long-term outcomes of device-based closure of atrial septal defects (ASDs) with no sizing balloon. MATERIAL AND METHODS: Two hundred and eighty-one consecutive patients (mean age 34±13 years, 178 women) underwent intracardiac echocardiography (ICE)-aided transcatheter closure of secundum ASDs over a 15-year period (September 2002 to March 2017). Sizing of the ASDs was calculated under ICE guidance (UltraICE, EP Technologies, Boston Scientific Corporation, San Jose, CA, USA) using the concept of "supportive rim" for ASDs without the aid of a sizing balloon. Follow-up was conducted by transoesophageal and transthoracic echocardiography. RESULTS: The procedure was carried out successfully in all patients with 0% related mortality and 5.7% procedural complications. The Amplatzer ASD Occluder was implanted in 251 patients (89.3%, mean size 26.4±10.2 mm) whereas the Gore Cardioform was used in 30 patients (10.6%). Over 10.3±3 years of follow-up (range 1-15) 100% of patients were alive. The complete occlusion rate was 97.8%. No aortic or atrial free wall erosions, device thrombosis, or device frame fractures were detected during the follow-up period. CONCLUSION: The present study suggested that ICE-guided closure of ASDs with current devices without sizing balloons is safe and effective with very low procedural and late complications even in the very long-term follow-up.

Metastatic pattern and new primary tumours after neoadjuvant therapy and surgery in rectal cancer.

AIM: Current follow-up guidelines for distant tumour recurrence after rectal cancer surgery are not defined or agreed. The aim was to elucidate the pattern of recurrence over time and provide information that could help direct a strategy for surveillance. METHOD: In all, 378 patients with locally advanced rectal cancer were treated with preoperative chemoradiotherapy and surgery with curative intent. Patients were followed up with a standard protocol, and data were prospectively collected in a dedicated database. Disease-free survival and overall survival were calculated. RESULTS: Within a median follow-up time of 75 months, rates of local and distant recurrence were 2.6% and 21.7%, respectively. Risk factors for recurrence were a baseline carcinoembryonic antigen > 5.0 ng/ml, a distance from the anal verge ≤ 5 cm, R1 resection margins, G3 grading, ypT staging > 2, positive lymph node status and a tumour regression grade of 3-5. Disease-free survival did not vary significantly between patients with lung and extra-pulmonary metastases (P = 0.59). The only factor associated with increased risk of lung metastases was a distance of the tumour from the anal verge of ≤ 5 cm (P = 0.01). Most recurrences occurred within the first 3 years after surgery (74.4%). The first site of recurrence was most frequently the lung (52.0%). The most frequent new primary malignancy was lung cancer (22.5%). CONCLUSIONS: Patients undergoing curative therapy for rectal cancer often experience distant recurrence; the majority of recurrences occur within the first 3 years after surgery and lung metastases are the most common. A predictive factor for pulmonary recurrence is a tumour in the lower rectum.

Allogeneic mesenchymal stem cells improve the wound healing process of sheep skin.

BACKGROUND: Skin wound healing includes a system of biological processes, collectively restoring the integrity of the skin after injury. Healing by second intention refers to repair of large and deep wounds where the tissue edges cannot be approximated and substantial scarring is often observed. The objective of this study was to evaluate the effects of mesenchymal stem cells (MSCs) in second intention healing using a surgical wound model in sheep. MSCs are known to contribute to the inflammatory, proliferative, and remodeling phases of the skin regeneration process in rodent models, but data are lacking for large animal models. This study used three different approaches (clinical, histopathological, and molecular analysis) to assess the putative action of allogeneic MSCs at 15 and 42 days after lesion creation. RESULTS: At 15 days post-lesion, the wounds treated with MSCs showed a higher degree of wound closure, a higher percentage of re-epithelialization, proliferation, neovascularization and increased contraction in comparison to a control group. At 42 days, the wounds treated with MSCs had more mature and denser cutaneous adnexa compared to the control group. The MSCs-treated group showed an absence of inflammation and expression of CD3+ and CD20+. Moreover, the mRNA expression of hair-keratine (hKER) was observed in the MSCs-treated group 15 days after wound creation and had increased significantly by 42 days post-wound creation. Collagen1 gene (Col1α1) expression was also greater in the MSCs-treated group compared to the control group at both days 15 and 42. CONCLUSION: Peripheral blood-derived MSCs may improve the quality of wound healing both for superficial injuries and deep lesions. MSCs did not induce an inflammatory response and accelerated the appearance of granulation tissue, neovascularization, structural proteins, and skin adnexa.

High efficacy of direct-acting anti-viral agents in hepatitis C virus-infected cirrhotic patients with successfully treated hepatocellular carcinoma.

BACKGROUND: The efficacy of direct-acting anti-viral (DAA) therapy in patients with a history of hepatocellular carcinoma (HCC) is unknown. AIM: We prospectively evaluated whether previously treated HCC affects DAA efficacy in a large real-life cohort of cirrhotic patients. METHODS: From January to December 2015 all consecutive HCV mono-infected patients with cirrhosis and/or history of HCC attending 10 Italian tertiary liver centres were enrolled. Baseline characteristics and response to therapy were recorded. 1927 patients were enrolled (mean age: 62.1 ± 10.9 years; 1.205 males). Genotype 1 was the most frequent (67.9%) followed by genotypes 3 (12.4%), 2 (11.2%) and 4 (8.6%). 88.4% and 10.9% of cases were classified Child A and B, respectively, and 14 (<1%) cases were classified Child C. Ascites and hepatic encephalopathy occurred in 10.7% and 3.2% of patients, respectively. Varices were detected in 39.3% of patients. Suboptimal and optimal treatment was prescribed: 15.9% of patients received sofosbuvir/simeprevir, 33.4% sofosbuvir/ledipasvir, 20.2% a Viekirax + Exviera regimen, 15.7% sofosbuvir/ribavirin, 9.9% sofosbuvir/daclatasvir and 3.4% Viekirax; 1.3% of patients received an interferon-based regimen. RESULTS: The sustained virologic response (SVR) rate at intention-to-treat analysis was 95.1%. It differed significantly across Child classes, that is, 96.3%, 86.1% and 71.4% Child A, B and C, respectively (P < 0.0001) and across genotypes (P = 0.002). The SVR rate did not differ between patients with (95.0%) and those without previous HCC (95.1%). At multivariable analysis, SVR was significantly associated with HCV genotype, Child class. CONCLUSION: This large real-life study proves that the efficacy of DAA in cirrhotic patients is not impaired by successfully treated HCC.

Antibacterial efficacy and mechanisms of action of low power atmospheric pressure cold plasma: membrane permeability, biofilm penetration and antimicrobial sensitization.

AIM: The objective of this study was to determine the efficacy and mechanisms of inactivation of two clinically relevant ESKAPE bacteria namely Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus by atmospheric pressure cold plasma. METHODS AND RESULTS: Plasma was generated between two brass grids by applying a radiofrequency electric field to a flow of helium. Intracellular generation of reactive species, alterations in cell membrane, and inactivation of bacteria in planktonic or biofilm growth were studied. Results were compared with commonly used antimicrobial drugs. Plasma exposure generated reactive oxygen and nitrogen species in bacteria, disrupted membrane integrity and reduced bacterial load. The efficacy in bacterial inactivation was comparable to antibiotics but exhibited a quicker killing rate. The antibacterial effect of plasma synergistically increased in association with antibiotics and did not diminish over repeated exposures, suggesting no development in bacterial resistance. CONCLUSIONS: Through generation of reactive species, cold plasma altered cell membrane and effectively inactivated clinically important bacteria, both in suspension and in biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: As cold plasma damages different targets in bacterial cells, it emerges as an effective strategy used alone or in combination with antimicrobial drugs to control microbial infections and prevent the selection of resistant bacterial strains.

In-hospital mortality, 30-day readmission, and length of hospital stay after surgery for primary colorectal cancer: A national population-based study.

INTRODUCTION: The simultaneous assessment of multiple indicators for quality of care is essential for comparisons of performance between hospitals and health care systems. The aim of this study was to assess the rates of in-hospital mortality and 30-day readmission and length of hospital stay (LOS) in patients who underwent surgical procedures for colorectal cancer between 2005 and 2014 in Italy. METHODS: All patients in the National Italian Hospital Discharge Dataset who underwent a surgical procedure for colorectal cancer during the study period were included. The adjusted odd ratios for risk factors for in-hospital mortality, 30-day readmission, and LOS were calculated using multilevel multivariable logistic regression. RESULTS: Among the 353 941 patients, rates of in-hospital mortality and 30-day readmission were 2.5% and 6%, respectively, and the median LOS was 13 days. High comorbidity, emergent/urgent admission, male gender, creation of a stoma, and an open approach increased the risks of all the outcomes at multivariable analysis. Age, hospital volume, hospital geographic location, and discharge to home/non-home produced different effects depending on the outcome considered. The most frequent causes of readmission were infection (19%) and bowel obstruction (14.6%). CONCLUSIONS: We assessed national averages for mortality, LOS and readmission and related trends over a 10-year time. Laparoscopic surgery was the only one that could be modified by improving surgical education. Higher hospital volume was associated with a LOS reduction, but our findings only partially support a policy of centralization for colorectal cancer procedures. Surgical site infection was identified as the most preventable cause of readmission.

Seroepidemiology of HEV and HAV in two populations with different socio-economic levels and hygienic/sanitary conditions.

The epidemiological scenarios of hepatitis E virus (HEV) and hepatitis A virus (HAV) infections have changed in the last few decades, but precise epidemiological data on the prevalence of anti-HEV and anti-HAV, alone or in combination, in the general population are scanty. We investigated HEV and HAV seroprevalence comparing two population samples living in Northern (Abbiategrasso, Milan) and Southern Italy (Cittanova, Reggio Calabria), the latter being characterized by a poorer socio-economic level and hygienic/sanitary conditions. Based on census records, we randomly enrolled and tested 3,365 subjects (Abbiategrasso, n = 2,489; Cittanova, n = 876) aged 18-75 years for anti-HAV and anti-HEV. Anti-HAV (71.3 % vs 52.5 %) and anti-HEV (17.8 % vs 9.0 %) prevalence rates were higher in Southern Italy (both p < 0.001). Most anti-HEV-positive subjects also had anti-HAV. Subjects testing positive for anti-HAV, alone or with anti-HEV, were older (p < 0.001 in both populations) and showed a trend toward declining prevalence in the youngest birth cohorts. The prevalence of subjects with a positive result for anti-HEV alone did not change in birth cohorts in the two towns. Detection of anti-HEV was independently associated with anti-HAV, town, birth cohort, and education level in multivariate analysis. Low socio-economic level and hygienic/sanitary conditions are associated with high HAV and HEV seroprevalence rates in Italy. Recent improvements, especially in the South, have led to a declining prevalence of anti-HAV, alone or with anti-HEV. Seroprevalence of HEV alone is uniformly low and does not change in birth cohorts born between 1938 and 1993.

Effects of the Antihypertensive Fixed-Dose Combinations on an Early Marker of Hypertensive Cardiac Damage in Subjects at Low Cardiovascular Risk.

BACKGROUND: In hypertensive subjects (HTs), isolated left ventricular diastolic dysfunction (LVDD) is an early marker of cardiac damage and is associated with poor prognosis. However, few intervention trials investigated the effects of antihypertensive therapy on isolated LVDD regression. This study investigates the blood pressure (BP)-lowering efficacy and the effect on LVDD of antihypertensive drugs administered as fixed-dose combinations in untreated HTs with isolated LVDD. METHODS: A total of 168 HTs (23% of them having impaired fasting glucose (IFG)) aged 48±4.2 years were randomized to receive open-label once-daily oral treatment of beta-blocker + diuretic, angiotensin-converting enzyme inhibitor (ACEI) + diuretic, angiotensin II receptor blocker (ARB) + diuretic, ARB + calcium channel blocker (CCB), or ACEI + CCB. Clinic and 24-hour ambulatory BP values were measured before randomization and at the follow-up. Regression of LVDD was defined as normalization of both the E/A (ratio of early-to-late ventricular filling wave velocity) and E/E' (mitral velocity to early diastolic velocity of the mitral annulus) ratios. Comparisons were made between categorical variables using the χ(2) test and between continuous variables by gender using analysis of variance for repeated measures. RESULTS: BP reduction did not differ between groups. LVDD regression was significantly more prevalent in the ARB + CCB or ACEI + CCB groups than with other combinations; in HTs with IFG, it was most prevalent (46%) with ACEI + CCB. CONCLUSIONS: Independently of BP reduction, the fixed-dose combinations ARB + CCB and ACEI + CCB led to regression of isolated LVDD. In those with an IFG, ACEI + CCB was most effective.

(99m)Tc-DTPA scintigraphy assesses the absence of glomerular filtration rate impairment of Aliskiren in high-risk hypertensive subjects. A 12-month follow-up study.

AIM: Glomerular filtration rate (GFR) is commonly calculated using the modification of diet in renal disease (MDRD) and Cockroft-Gault (CG) formulas and recently by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) algorithm and not directly measured, so that the real impact of antihypertensive therapy on GFR could not be well defined. In this study, the effect of Aliskiren on the GFR measured by radionuclide clearance of 99mTc-diethylene triamine penta-acetic acid (DTPA) was investigated. METHODS: In 106 hypertensive subjects (53% men) aged 61.9±12.7 years with uncontrolled blood pressure (BP) receiving at least 2 antihypertensive medications, Aliskiren was added once-daily at a dose of 150-300 mg for 12 months. Clinic BP measurements were taken at every follow-up visit (1st, 6th and 12th month), while 24-hours ambulatory BP and GFR (in mL/min/1.73 m2) were evaluated at baseline and at the end of the follow-up. Analysis of variance for repeated measures of BP, GFR and microalbuminuria was provided. RESULTS: With the use of Aliskiren a significant reduction of BP and microalbuminuria was found (P<0.0001). Only in male population, a significant reduction in GFR calculated with CKD-EPI (82.4±15 vs. 78.6±18.2, P<0.01) and CG (81.6±29.5 vs. 74.2±28.4, P<0.0001) formulas was observed. This impairment of GFR was not found either with MDRD formula (70.5±19.6 vs. 68.3±23.4) or by radionuclide clearance (62.4±18.6 vs. 61.4±20.5). CONCLUSION: This study seems to demonstrate that the efficacy on BP control of Aliskiren is not accompanied by an impairment of GFR. In order to evaluate the effect of Aliskiren on GFR scintigraphy technique or MDRD formula resulted to be the most accurate methods.