Publications by authors named "Marco Russo"

166 Publications

Pioglitazone even at low dosage improves NAFLD in type 2 diabetes: clinical and pathophysiological insights from a subgroup of the TOSCA.IT randomised trial.

Diabetes Res Clin Pract 2021 Jul 23:108984. Epub 2021 Jul 23.

Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.

Aims: Non-Alcoholic Fatty Liver Disease (NAFLD) and type 2 diabetes (T2D) share pathophysiological mechanisms and possible therapeutic strategies. We evaluated the effects of 1-year treatment with pioglitazone or sulphonylureas on indirect indices of NAFLD in people with T2D and the role of insulin-resistance and glucotoxicity in determining these effects.

Methods: patients with T2D (n=195) aged 50-75 years, poorly controlled with metformin 2 g/day, were randomly allocated to add-on pioglitazone (n=98) or sulphonylureas (n=97) within the TOSCA.IT trial. Plasma insulin, glucose, and liver enzymes were measured at baseline and after 1-year. Indirect indices of NAFLD (Liver Fat Equation [LFE], Hepatic Steatosis Index [HSI], and Index of NASH [ION]), and insulin resistance (HOMA-IR, Visceral Adiposity Index [VAI] and adipose tissue Insulin Resistance [ADIPO-IR]) were calculated.

Results: indices of NAFLD improved after pioglitazone, but not after sulphonylureas; differences between changes (1-year minus baseline) were respectively: -1.76±3.84 vs. 0.28±3.75 for LFE; -1.35±2.78 vs. -0.27±2.63 for HSI; -9.75±43 vs. 3.24±31 for ION; p<0.05 for all. Indices of insulin resistance decreased after pioglitazone, but not after sulphonylureas: -0.95±4.57 vs. 0.37±3.34 for HOMA-IR, p=0.032; -1.25±4.11 vs. 1.36±5.43 for ADIPO-IR, p=0.001; -0.53±1.88 vs. 0.03±2.36 for VAI, p=0.074. Changes in NAFLD indices were similar with different doses of pioglitazone (15, 30, or 45 mg/day), and were independent of blood glucose control.

Conclusions: one-year treatment with pioglitazone even at low dosage significantly improved liver steatosis and inflammation, systemic and adipose tissue insulin resistance in patients with T2D. The beneficial effects of pioglitazone on NAFLD were independent of blood glucose control. Clinical Trials.gov number:NCT00700856.
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http://dx.doi.org/10.1016/j.diabres.2021.108984DOI Listing
July 2021

Erucic acid concentration of rapeseed ( L.) oils on the German food retail market.

Food Sci Nutr 2021 Jul 11;9(7):3664-3672. Epub 2021 May 11.

Institute of Agronomy & Plant Breeding I Justus Liebig University Giessen Giessen Germany.

Rapeseed oil is one of the most important vegetable oils in Germany. It has a favorable fatty acid composition but also contains a certain amount of erucic acid (EA). As the result of toxicological considerations regarding this fatty acid, the European Food Safety Authority (EFSA) established a tolerable daily intake (TDI) for EA of 7 mg/kg body weight in 2016. On this basis, the maximum EA levels for vegetable oils allowed in the European Union have been reduced shortly from 50 to 20 g/kg, and for infant formula and follow-on formula from 10 to 4 g/kg. However, rapeseed oil is also recommended for the preparation of homemade food for infants and children. Little is known about the actual EA concentrations of rapeseed oils on the German retail market. Current data are especially important for the necessary reassessment of its recommendation in infant and child nutrition based on the established TDI. Three hundred representative rapeseed oil samples were purchased in retail stores across Germany. EA concentrations, determined by GC-FID, were in a range of 0.17-9.68 g/kg, with 241 samples being even below 4 g/kg. All oils were below the maximum level valid at the time of this investigation, and even below the newly established lower maximum level of 20 g/kg. The major part also met the requirements for infant and follow-on formula. The representative results provide valuable current data for the necessary reassessment of the dietary recommendations for infant and child nutrition based on the established TDI.
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http://dx.doi.org/10.1002/fsn3.2327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269665PMC
July 2021

Total knee arthroplasty in a young patient with achondroplasia.

BMJ Case Rep 2021 Jul 8;14(7). Epub 2021 Jul 8.

Villa Erbosa Hospital, Bologna, Italy.

Achondroplasia is a genetic skeletal dysplasia, characterised by dwarfism, with upper and lower limb deformities, that can lead to knee osteoarthritis; the surgical treatment is a challenge due to the particular joint anatomy variances. We present a 40-year-old woman, affected by achondroplasia with severe left knee osteoarthritis; the patient was treated conservatively with poor results. Between the ages of 12 and 17 years, she underwent multiple operative procedures for lower limb lengthening and a partial correction of the valgus deformity, by applying an external fixator. The patient was successfully treated with cemented posterior stabilised, fixed-bearing, total knee arthroplasty. The patient affected by achondroplasia, with severe knee osteoarthritis, should be considered for total joint replacement, which can be carried out with or without additional extra-articular osteotomy for alignment correction. Due to skeletal dysplasia in joint deformities, knee replacement requires careful preoperative planning and special technical considerations.
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http://dx.doi.org/10.1136/bcr-2021-242909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268906PMC
July 2021

G-quadruplex binders as cytostatic modulators of innate immune genes in cancer cells.

Nucleic Acids Res 2021 07;49(12):6673-6686

Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, via Selmi 3, 40126 Bologna, Italy.

G-quadruplexes (G4s) are non-canonical nucleic acid structures involved in fundamental biological processes. As G4s are promising anticancer targets, in past decades the search for effective anticancer G4 binders aimed at the discovery of more cytotoxic ligands interfering with specific G4 structures at oncogenes or telomeres. Here, we have instead observed a significant activation of innate immune genes by two unrelated ligands at non-cytotoxic concentrations. The studied G4 binders (pyridostatin and PhenDC3) can induce an increase of micronuclei triggering the activation of the cytoplasmic STING (stimulator of interferon response cGAMP interactor 1) signaling pathway in human and murine cancer cells. Ligand activity can then lead to type I interferon production and innate immune gene activation. Moreover, specific gene expression patterns mediated by a G4 binder in cancer cells correlate with immunological hot features and better survival in human TCGA (The Cancer Genome Atlas) breast tumors. The findings open to the development of cytostatic G4 binders as effective immunomodulators for combination immunotherapies in unresponsive tumors.
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http://dx.doi.org/10.1093/nar/gkab500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266585PMC
July 2021

Correction to article 'G-quadruplex-R-loop interactions and the mechanism of anticancer G-quadruplex binders'.

Nucleic Acids Res 2021 Jun;49(10):6000-6001

Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, via Selmi 3, 40126 Bologna, Italy.

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http://dx.doi.org/10.1093/nar/gkab483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191755PMC
June 2021

Imaging of Canine Neoplastic Reproductive Disorders.

Animals (Basel) 2021 Apr 22;11(5). Epub 2021 Apr 22.

Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy.

Diagnostic imaging plays an essential role in the diagnosis and management of reproductive neoplasia in dogs and cats. The initial diagnosis, staging, and planning of surgical and radiation treatment and the response to therapy all involve imaging to varying degrees. Routine radiographs, ultrasound, nuclear medicine, and cross-sectional imaging in the form of computed tomography (CT) and magnetic resonance imaging (MRI) are routinely used in canine reproductive disorders. The choice of imaging modality depends on many factors, including the level of referral and the pathological information required. The biological behaviour of the tumour also guides the choice of imaging in cancer staging, and imaging may play an important role in guiding serial tumour biopsy during the course of therapy. The sophistication of imaging modalities is increasing exponentially. Each modality has advantages and disadvantages in terms of cost, availability, sensitivity, specificity, and qualities of anatomic versus functional imaging.
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http://dx.doi.org/10.3390/ani11051213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146485PMC
April 2021

Robotic transareolar mitral valve repair.

Multimed Man Cardiothorac Surg 2021 04 21;2021. Epub 2021 Apr 21.

Cardiac Surgery and Heart Transplantation Department, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy

In recent years, the treatment of mitral valve disease with robotic surgery has been increasingly successful, having produced excellent postoperative results and significant cost-savings. However, minimal  experience exists with robotic mitral valve repair using transareolar access. We demonstrate mitral valve repair using the DaVinci Robot Xi through a transareolar approach, showing the technical details of our surgical technique.
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http://dx.doi.org/10.1510/mmcts.2021.022DOI Listing
April 2021

Beating vs Arrested Heart Isolated Tricuspid Valve Surgery: Long-term Outcomes.

Ann Thorac Surg 2021 Apr 5. Epub 2021 Apr 5.

Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.

Background: Isolated tricuspid valve (TV) surgery is a rare procedure generally considered at high risk of perioperative mortality and poor long-term outcomes. Surgical treatment can be performed with either an arrested heart (AH) or beating heart (BH) technique. Aim of this study is to compare the outcomes of isolated tricuspid surgery with two different approaches.

Methods: The SUR-TRI study is a multicenter international retrospective study enrolling adult patients who underwent isolated tricuspid valve procedures (n=406, 56±16 years; 56% female) at 13 international sites. AH and BH strategies were performed in 253 and 153 cases, respectively. Propensity score-matched analysis was used to compare groups.

Results: After matching, 129 pairs were obtained and analyzed. The 30-day mortality rate was 6.2 vs 5.0% in the AH and BH groups, respectively (p=0.9). The rates of acute renal failure requiring replacement therapy (3 vs 10%, p=0.02) and stroke (0 vs 1.8%, p=0.08) were numerically higher in the AH group. The 6-year survival rate was 67±6 vs 78±5% in the AH and BH groups, respectively (p=0.18), while freedom from cardiac death was 75±5 vs 84±4% (p=0.21). The six-year composite cardiac endpoint of cardiac death and reoperation rate was 60±9 vs 86±5% (p=0.024) comparing AH-TV replacement and BH-TV repair groups.

Conclusions: Isolated tricuspid valve surgery performed with a beating heart strategy is a safe option and resulted in a trend of increased long-term survival and freedom from reoperation when compared with the standard arrested heart technique. Patients undergoing beating heart valve repair had the best long-term outcome.
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http://dx.doi.org/10.1016/j.athoracsur.2021.03.070DOI Listing
April 2021

B-Mode and Contrast Enhanced Ultrasonography Features of Gastric Inflammatory and Neoplastic Diseases in Dogs.

Animals (Basel) 2021 Mar 3;11(3). Epub 2021 Mar 3.

Faculty of Veterinary Medicine, University of Teramo, SP 18, 64100 Teramo, Italy.

Canine gastric disorders are common in veterinary clinical practice and among these neoplasms require rapid identification and characterization. Standard ultrasound (US) is the imaging modality of choice for gastric wall assessment. The aim of this prospective study is to describe the specific B-mode and contrast enhanced US (CEUS) features of normal, inflammatory, and neoplastic gastric wall in dogs. B-mode US and CEUS of the stomach were performed in anesthetized dogs with or without gastric disorders. Gastric wall qualitative and quantitative parameters were evaluated on B-mode US and CEUS examination. A total of 41 dogs were included: 6 healthy (HEA) as the control group; 9 gastritis (INF); 8 adenocarcinoma (AC); 8 alimentary lymphoma (AL); 4 leiomyosarcoma (LEIS); 2 gastrointestinal stromal tumor (GIST); 2 leiomyoma; 1 undifferentiated sarcoma; 1 metastatic gastric hemangiosarcoma. Gastric tumors appear as a marked wall thickness with absent layers definition and possible regional lymphadenopathy (AC and AL) and steatitis (AC) while gastritis generally shows no/mild thickening and no other alterations on B-mode US. On CEUS, neoplasm shows a higher and faster wash in if compared to that of gastritis. B-mode and CEUS assessment may be useful in the evaluation of canine gastric disorders in the distinction between gastritis and gastric neoplasms, even if there are no specific features able to discriminate between the different tumor histotypes.
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http://dx.doi.org/10.3390/ani11030670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998525PMC
March 2021

Pseudo-Placentational Endometrial Hyperplasia in the Bitch: Case Series.

Animals (Basel) 2021 Mar 6;11(3). Epub 2021 Mar 6.

Department of Veterinary Medicine and Animal Production, University of Naples, Federico II, 80137 Naples, Italy.

Canine pseudo-placentational endometrial hyperplasia differs from the classical form of cystic endometrial hyperplasia for the well-organized tissue architecture resembling the canine placenta. After the discovery, it has been inconstantly reported. The present work reports the clinicopathological details of six spontaneous cases retrieved retrospectively from a large database. The lesion was found in young non-pregnant female dogs (median 2.0 years) at the end of dioestrus. It could be imaged by ultrasound and was always grossly detectable as single or multiple uterine enlargements of 2-3 cm in diameter with a villous whitish tissue growing on the mucosa and occluding the lumen. Histology confirmed the tissue architecture of the canine placenta with a basal glandular layer, a connective band, a spongy layer and a tortuous and compact labyrinth, often poorly recognizable. The pseudo-placentational hyperplasia is a non-inflammatory proliferative lesion although numerous mast cells inhabit the connective band, and a superimposed inflammatory infiltrate was seen in a case. Canine pseudo-placentational endometrial hyperplasia has very peculiar features, and it is a model for canine placentation and may help to better understand the cystic endometrial hyperplasia/pyometra complex.
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http://dx.doi.org/10.3390/ani11030718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000527PMC
March 2021

High efficacy of onabotulinumtoxinA treatment in patients with comorbid migraine and depression: a meta-analysis.

J Transl Med 2021 03 31;19(1):133. Epub 2021 Mar 31.

Department of Neuroscience, University of Uppsala, Uppsala, Sweden.

Background: Migraine and depression are highly prevalent and partly overlapping disorders that cause strong limitations in daily life. Patients tend to respond poorly to the therapies available for these diseases. OnabotulinumtoxinA has been proven to be an effective treatment for both migraine and depression. While many studies have addressed the effect of onabotulinumtoxinA in migraine or depression separately, a growing body of evidence suggests beneficial effects also for patients comorbid with migraine and depression. The current meta-analysis systematically investigates to what extent onabotulinumtoxinA is efficient in migraineurs with depression.

Methods: A systematic literature search was performed based on PubMed, Scopus and Web of Science from the earliest date till October [Formula: see text], 2020. Mean, standard deviation (SD) and sample size have been used to evaluate improvement in depressive symptoms and migraine using random-effects empirical Bayes model.

Results: Our search retrieved 259 studies, eight of which met the inclusion criteria. OnabotulinumtoxinA injections administered to patients with both chronic migraine and major depressive disorder led to mean reduction of [Formula: see text] points (CI [[Formula: see text]], [Formula: see text]) in the BDI scale, of [Formula: see text] points (CI [[Formula: see text]], [Formula: see text]) in the BDI-II scale and of [Formula: see text] points (CI [[Formula: see text]], [Formula: see text]) in the PHQ-9 scale, when evaluating depressive symptoms. In the case of the migraine-related symptoms, we found mean reductions of [Formula: see text] (CI [[Formula: see text]], [Formula: see text]) points in the HIT6 scale, [Formula: see text] (CI [[Formula: see text]], [Formula: see text]) in the MIDAS scale, [Formula: see text] (CI [[Formula: see text]], [Formula: see text]) points in the VAS scale and of [Formula: see text] (CI [[Formula: see text]], [Formula: see text]) migraine episodes per month. Comorbid patients showed slightly better improvements in BDI, HIT6 scores and migraine frequency compared to monomorbid patients. The latter group manifested better results in MIDAS and VAS scores.

Conclusion: Treatment with onabotulinumtoxinA leads to a significant reduction of disease severity of both chronic migraine and major depressive disorder in patients comorbid with both diseases. Comparative analyses suggest an equivalent strong effect in monomorbid and comorbid patients, with beneficial effects specifically seen for certain migraine features.
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http://dx.doi.org/10.1186/s12967-021-02801-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011097PMC
March 2021

Early Management of OnabotulinumtoxinA Treatment in Chronic Migraine: Insights from a Real-Life European Multicenter Study.

Pain Ther 2021 Jun 28;10(1):637-650. Epub 2021 Mar 28.

Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant'Andrea Hospital, Sapienza University, 00189, Rome, RM, Italy.

Introduction: OnabotulinumtoxinA (BT-A) quarterly was the first treatment approved specifically for chronic migraine (CM). It is unclear whether three cycles are better than two to assess early BT-A response.

Methods: We performed a retrospective analysis on real-life prospectively collected data in 16 European headache centers. All the centers provided data on patients treated with BT-A for CM over the first three cycles of treatment. For each treatment cycle we defined patients as "good responders" if reporting a ≥ 50% reduction in monthly headache days compared with the three months before starting BT-A, "partial responders" if reporting a 30-49% reduction in monthly headache days, and "non-responders" if reporting a < 30% reduction in monthly headache days or stopping the treatment before the third cycle.

Results: We included 2879 patients. Seven hundred and eighty-four (64.6%) of the 1213 patients reporting a good response during the first and/or the second cycle had a good response during the third cycle; 309 (49.3%) of the 627 patients reporting a partial response (but no good response) during the first and/or the second cycle had a good response during the third cycle; only 65 (6.3%) of the 1039 patients who did not respond during both the first two cycles achieved a good response during the third cycle. Multivariate analyses showed that partial or good response during the first or the second cycle were independently associated with good response during the third cycle.

Conclusions: Our data suggest that patients with CM responding to BT-A during the first two cycles will likely benefit from the third cycle of treatment, while the probability that non-responders to the first two cycles start responding during the third cycle is low. These results can help guide the individual decision to stop or continue treatment after the second cycle in patients who have not responded to the first two cycles.
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http://dx.doi.org/10.1007/s40122-021-00253-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119503PMC
June 2021

Contrast-Enhanced Ultrasound Imaging of Prostate Gland in Neutered Dogs.

Animals (Basel) 2021 Feb 20;11(2). Epub 2021 Feb 20.

Department of Veterinary Medicine and Animal Production, University of Naples, Federico II, 80137 Naples, Italy.

Prostatic neoplasia (PN) occurs in 5-7% of dogs with prostatic disease, with castrated dogs having the same or higher prevalence when compared to intact dogs. Considering the promising results achieved by performing contrast-enhanced ultrasound (CEUS) in intact dogs to detect PN, the present study aimed to acquire data on the prostatic perfusion pattern in neutered dogs. CEUS was performed in 64 neutered dogs, using a 5-7.5 MHz linear transducer with coded harmonic capability, dedicated analytical software, and a second-generation contrast agent, SonoVue. After B-mode evaluation was performed to assess mean prostate volume, the CEUS examination was undertaken. The flow of contrast agent was visible 10 s after injection. The subcapsular vessels were highlighted and produced rapid peripheral rim enhancement. Subsequently, the contrast agent reached the prostatic urethra via the parenchymal arterioles and gradually reached the entire prostate. Perfusion peak intensity (PPI) and time to peak (TTP) values were respectively 45.3% and 34.1 s. The measured parameters were compared with those obtained in previous studies on intact dogs with normal and with pathological patterns. In this study, CEUS showed features that may be promising for its use as a diagnostic tool for early detection of PN in neutered dogs.
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http://dx.doi.org/10.3390/ani11020559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924405PMC
February 2021

Artificial intelligence in health data analysis: The Darwinian evolution theory suggests an extremely simple and zero-cost large-scale screening tool for prediabetes and type 2 diabetes.

Diabetes Res Clin Pract 2021 Apr 27;174:108722. Epub 2021 Feb 27.

Department of Physics and Astronomy, University of Catania, Catania, Italy; INFN - Sezione di Catania, Catania, Italy.

Aims: The effective identification of individuals with early dysglycemia status is key to reduce the incidence of type 2 diabetes. We develop and validate a novel zero-cost tool that significantly simplifies the screening of undiagnosed dysglycemia.

Methods: We use NHANES cross-sectional data over 10 years (2007-2016) to derive an equation that links non-laboratory exposure variables to the possible presence of undetected dysglycemia. For the first time, we adopt a novel artificial intelligence approach based on the Darwinian evolutionary theory to analyze health data. We collected data for 47 variables.

Results: Age and waist circumference are the only variables required to use the model. To identify undetected dysglycemia, we obtain an area under the curve (AUC) of 75.3%. Sensitivity and specificity are 0.65 and 0.73 by using the optimal threshold value determined from external validation data.

Conclusions: The use of uniquely two variables allows to obtain a zero-cost screening tool of analogous precision than that of more complex tools widely adopted in the literature. The newly developed tool has clinical use as it significantly simplifies the screening of dysglycemia. Furthermore, we suggest that the definition of an age-related waist circumference cut-off might help to improve existing diabetes risk factors.
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http://dx.doi.org/10.1016/j.diabres.2021.108722DOI Listing
April 2021

Transcatheter Tricuspid Valve Intervention in Patients With Previous Left Valve Surgery.

Can J Cardiol 2021 Jul 19;37(7):1094-1102. Epub 2021 Feb 19.

Cardiology Department, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain.

Background: Scarce data exist on patients with previous left valve surgery (PLVS) undergoing transcatheter tricuspid valve intervention (TTVI). This study sought to investigate the procedural and early outcomes in patients with PLVS undergoing TTVI.

Methods: This was a subanalysis of the multicenter TriValve registry including 462 patients, 82 (18%) with PLVS. Data were analyzed according to the presence of PLVS in the overall cohort and in a propensity score-matched population including 51 and 115 patients with and without PLVS, respectively.

Results: Patients with PLVS were younger (72 ± 10 vs 78 ± 9 years; p < 0.01) and more frequently female (67.1% vs 53.2%; P = 0.02). Similar rates of procedural success (PLVS 80.5%; no-PLVS 82.1%; P = 0.73), and 30-day mortality (PLVS 2.4%, no-PLVS 3.4%; P = 0.99) were observed. After matching, there were no significant differences in both all-cause rehospitalisation (PLVS 21.1%, no-PLVS 26.5%; P = 0.60) and all-cause mortality (PLVS 9.8%, no-PLVS 6.7%; P = 0.58). At last follow-up (median 6 [interquartile range 1-12] months after the procedure), most patients (81.8%) in the PLVS group were in NYHA functional class I-II (P = 0.12 vs no-PLVS group), and TR grade was ≤ 2 in 82.6% of patients (P = 0.096 vs no-PVLS group). A poorer right ventricular function and previous heart failure hospitalization determined increased risks of procedural failure and poorer outcomes at follow-up, respectively.

Conclusions: In patients with PLVS, TTVI was associated with high rates of procedural success and low early mortality. However, about one-third of patients required rehospitalisation or died at midterm follow-up. These results would support TTVI as a reasonable alternative to redo surgery in patients with PLVS and suggest the importance of earlier treatment to improve clinical outcomes.
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http://dx.doi.org/10.1016/j.cjca.2021.02.010DOI Listing
July 2021

Transcatheter Tricuspid Valve Intervention in Patients With Right Ventricular Dysfunction or Pulmonary Hypertension: Insights From the TriValve Registry.

Circ Cardiovasc Interv 2021 02 5;14(2):e009685. Epub 2021 Feb 5.

Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain (R.E.-L., V.M.).

Background: Scarce data exist on patients with right ventricular dysfunction (RVD) or pulmonary hypertension (PH) undergoing transcatheter tricuspid valve intervention. This study aimed to determine the early and midterm outcomes and the factors associated with mortality in this group of patients.

Methods: This subanalysis of the multicenter TriValve (Transcatheter Tricuspid Valve Therapies) registry included 300 patients with severe tricuspid regurgitation with RVD (n=244), PH (n=127), or both (n=71) undergoing transcatheter tricuspid valve intervention. RVD was defined as a tricuspid annular plane systolic excursion <17 mm, and PH as an estimated pulmonary artery systolic pressure ≥50 mm Hg.

Results: Mean age of the patients was 77±9 years (54% women). Procedural success was 80.7%, and 9 patients (3%) died during the hospitalization. At a median follow-up of 6 (interquartile range, 2-12) months, 54 patients (18%) died, and the independent associated factors were higher gamma-glutamyl transferase values at baseline (hazard ratio, 1.02 for each increase of 10 u/L [95% CI, 1.002-1.04]), poorer renal function defined as an estimated glomerular filtration rate <45 mL/min (hazard ratio, 2.3 [95% CI, 1.22-4.33]), and the lack of procedural success (hazard ratio, 2.11 [95% CI, 1.17-3.81]). The grade of RVD and the amount of PH at baseline were not found to be predictors of mortality. Most patients alive at follow-up improved their functional class (New York Heart Association I-II in 66% versus 7% at baseline, <0.001).

Conclusions: In patients with severe tricuspid regurgitation and RVD/PH, transcatheter tricuspid valve intervention was associated with high procedural success and a relatively low in-hospital mortality, along with significant improvements in functional status. However, about 1 out of 5 patients died after a median follow-up of 6 months, with hepatic congestion, renal dysfunction, and the lack of procedural success determining an increased risk. These results may improve the clinical evaluation of transcatheter tricuspid valve intervention candidates and would suggest a closer follow-up in those at increased risk. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03416166.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.009685DOI Listing
February 2021

Transcatheter Replacement of Transcatheter Versus Surgically Implanted Aortic Valve Bioprostheses.

J Am Coll Cardiol 2021 01;77(1):1-14

Herzzentrum Duisburg, Duisburg, Germany.

Background: Surgical aortic valve replacement and transcatheter aortic valve replacement (TAVR) are now both used to treat aortic stenosis in patients in whom life expectancy may exceed valve durability. The choice of initial bioprosthesis should therefore consider the relative safety and efficacy of potential subsequent interventions.

Objectives: The aim of this study was to compare TAVR in failed transcatheter aortic valves (TAVs) versus surgical aortic valves (SAVs).

Methods: Data were collected on 434 TAV-in-TAV and 624 TAV-in-SAV consecutive procedures performed at centers participating in the Redo-TAVR international registry. Propensity score matching was applied, and 330 matched (165:165) patients were analyzed. Principal endpoints were procedural success, procedural safety, and mortality at 30 days and 1 year.

Results: For TAV-in-TAV versus TAV-in-SAV, procedural success was observed in 120 (72.7%) versus 103 (62.4%) patients (p = 0.045), driven by a numerically lower frequency of residual high valve gradient (p = 0.095), ectopic valve deployment (p = 0.081), coronary obstruction (p = 0.091), and conversion to open heart surgery (p = 0.082). Procedural safety was achieved in 116 (70.3%) versus 119 (72.1%) patients (p = 0.715). Mortality at 30 days was 5 (3%) after TAV-in-TAV and 7 (4.4%) after TAV-in-SAV (p = 0.570). At 1 year, mortality was 12 (11.9%) and 10 (10.2%), respectively (p = 0.633). Aortic valve area was larger (1.55 ± 0.5 cm vs. 1.37 ± 0.5 cm; p = 0.040), and the mean residual gradient was lower (12.6 ± 5.2 mm Hg vs. 14.9 ± 5.2 mm Hg; p = 0.011) after TAV-in-TAV. The rate of moderate or greater residual aortic regurgitation was similar, but mild aortic regurgitation was more frequent after TAV-in-TAV (p = 0.003).

Conclusions: In propensity score-matched cohorts of TAV-in-TAV versus TAV-in-SAV patients, TAV-in-TAV was associated with higher procedural success and similar procedural safety or mortality.
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http://dx.doi.org/10.1016/j.jacc.2020.10.053DOI Listing
January 2021

Correction to: G-quadruplex-R-loop interactions and the mechanism of anticancer G-quadruplex binders.

Nucleic Acids Res 2021 01;49(1):595

Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, via Selmi 3, 40126 Bologna, Italy.

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http://dx.doi.org/10.1093/nar/gkaa1206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797063PMC
January 2021

Structural valve deterioration after aortic valve replacement with the Trifecta valve.

Interact Cardiovasc Thorac Surg 2021 01;32(1):39-46

Division of Cardiac Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria.

Objectives: Despite promising short- and mid-term results for durability of the Trifecta valve, contradictory reports of early structural valve deterioration (SVD) do exist. We investigated the incidence of SVD after surgical aortic valve replacement (SAVR) with the Trifecta in our single-centre experience.

Methods: Data of 347 consecutive patients (mean age 71.6 ± 9.5 years, 63.4% male) undergoing SAVR with the Trifecta between 2011 and 2017 were analysed. Clinical and echocardiographic reports were obtained with a median follow-up of 41 months (1114 patient years).

Results: Isolated SAVR was performed in 122 patients (35.2%), whereas 225 patients (64.8%) underwent concomitant procedures. The median EuroSCORE II was 4.0 (0.9; 7.1) and 30-day mortality was 3.7% (n = 13). Kaplan-Meier estimates for the freedom of overall mortality at 1, 5 and 7 years were 88.7 ± 1.7%, 73.7 ± 2.6% and 64.7 ± 4.2%, respectively. SVD was observed in 25 patients (7.2%) with a median time to first diagnosis of 73 months. Freedom of SVD was 92.5 ± 0.9% at 5 years and 65.5 ± 7.1% at 7 years. Thirteen patients underwent reintervention for SVD (6 re-SAVR, 7 valve-in-valve), resulting in a freedom of reintervention for the SVD of 98.5 ± 1.1% at 5 years and 76.9 ± 6.9% at 7 years.

Conclusions: We herein report one of the highest rates of SVD after SAVR with the Trifecta. These data indicate that the durability of the prosthesis decreases at intermediate to long-term follow-up, leading to considerable rates of reintervention due to SVD.
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http://dx.doi.org/10.1093/icvts/ivaa236DOI Listing
January 2021

FSH Stimulation with Short Withdrawal Improves Oocyte Competence in Italian Mediterranean Buffalo ().

Animals (Basel) 2020 Oct 30;10(11). Epub 2020 Oct 30.

Department of Veterinary Medicine and Animal Production (DMVPA), Federico II University of Naples, 80137 Naples, Italy.

The aim of this work was to evaluate the efficiency of different FSH doses and FSH coasting times before ovum pick-up (OPU) on follicular growth and oocyte competence in buffalo. Experiment 1 involved two different FSH treatments: 40 mg FSH given three (FSH3) or six (FSH6) times, 2 days after dominant follicle removal were tested, with OPU carried out after 40-44 h of coasting. In experiment 2, OPU was carried out after FSH6 protocol followed by 28-32 h (C1), 40-44 h (C2), or 64-68 h (C3) of coasting time. Cumulus oocyte complexes (COCs) were classified, in vitro matured, fertilized, and cultured. The results demonstrated that FSH6 increased the total number of follicles, the number and percentages of medium and large follicles, the number and the proportion of good quality oocytes, and the number of grade 1,2 and fast-developing blastocysts compared to the control. C3 decreased the percentage of good quality oocyte and blastocyst rates compared to C1 and C2. A higher percentage of fast blastocysts and average number of grade 1,2 blastocysts was observed in C1 compared to C3, with intermediate values found in C2. The improved efficiency in terms of blastocyst yields suggests the use of FSH6 + C1 protocol for ovarian superstimulation in buffalo.
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http://dx.doi.org/10.3390/ani10111997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693096PMC
October 2020

G-quadruplex-R-loop interactions and the mechanism of anticancer G-quadruplex binders.

Nucleic Acids Res 2020 12;48(21):11942-11957

Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, via Selmi 3, 40126 Bologna, Italy.

Genomic DNA and cellular RNAs can form a variety of non-B secondary structures, including G-quadruplex (G4) and R-loops. G4s are constituted by stacked guanine tetrads held together by Hoogsteen hydrogen bonds and can form at key regulatory sites of eukaryote genomes and transcripts, including gene promoters, untranslated exon regions and telomeres. R-loops are 3-stranded structures wherein the two strands of a DNA duplex are melted and one of them is annealed to an RNA. Specific G4 binders are intensively investigated to discover new effective anticancer drugs based on a common rationale, i.e.: the selective inhibition of oncogene expression or specific impairment of telomere maintenance. However, despite the high number of known G4 binders, such a selective molecular activity has not been fully established and several published data point to a different mode of action. We will review published data that address the close structural interplay between G4s and R-loops in vitro and in vivo, and how these interactions can have functional consequences in relation to G4 binder activity. We propose that R-loops can play a previously-underestimated role in G4 binder action, in relation to DNA damage induction, telomere maintenance, genome and epigenome instability and alterations of gene expression programs.
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http://dx.doi.org/10.1093/nar/gkaa944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708042PMC
December 2020

Synaptic Organization of Anterior Olfactory Nucleus Inputs to Piriform Cortex.

J Neurosci 2020 12 28;40(49):9414-9425. Epub 2020 Oct 28.

Department of Neuroscience, Kavli Institute for Brain Science, Mortimer B. Zuckerman Mind Brain Behavior Institute, Department of Pharmacology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York

Odors activate distributed ensembles of neurons within the piriform cortex, forming cortical representations of odor thought to be essential to olfactory learning and behaviors. This odor response is driven by direct input from the olfactory bulb, but is also shaped by a dense network of associative or intracortical inputs to piriform, which may enhance or constrain the cortical odor representation. With optogenetic techniques, it is possible to functionally isolate defined inputs to piriform cortex and assess their potential to activate or inhibit piriform pyramidal neurons. The anterior olfactory nucleus (AON) receives direct input from the olfactory bulb and sends an associative projection to piriform cortex that has potential roles in the state-dependent processing of olfactory behaviors. Here, we provide a detailed functional assessment of the AON afferents to piriform in male and female C57Bl/6J mice. We confirm that the AON forms glutamatergic excitatory synapses onto piriform pyramidal neurons; and while these inputs are not as strong as piriform recurrent collaterals, they are less constrained by disynaptic inhibition. Moreover, AON-to-piriform synapses contain a substantial NMDAR-mediated current that prolongs the synaptic response at depolarized potentials. These properties of limited inhibition and slow NMDAR-mediated currents result in strong temporal summation of AON inputs within piriform pyramidal neurons, and suggest that the AON could powerfully enhance activation of piriform neurons in response to odor. Odor information is transmitted from olfactory receptors to olfactory bulb, and then to piriform cortex, where ensembles of activated neurons form neural representations of the odor. While these ensembles are driven by primary bulbar afferents, and shaped by intracortical recurrent connections, the potential for another early olfactory area, the anterior olfactory nucleus (AON), to contribute to piriform activity is not known. Here, we use optogenetic circuit-mapping methods to demonstrate that AON inputs can significantly activate piriform neurons, as they are coupled to NMDAR currents and to relatively modest disynaptic inhibition. The AON may enhance the piriform odor response, encouraging further study to determine the states or behaviors through which AON potentiates the cortical response to odor.
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http://dx.doi.org/10.1523/JNEUROSCI.0965-20.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724133PMC
December 2020

"Double-ring" combined aortic and mitral valve repair.

Indian J Thorac Cardiovasc Surg 2019 Oct 9;35(4):587-588. Epub 2018 Aug 9.

University Heart Center, UniversitätsSpital Zürich, University of Zürich, Rämistrasse 100, 8091 Zürich, Switzerland.

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http://dx.doi.org/10.1007/s12055-018-0716-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525895PMC
October 2019

Minimally invasive transatrial repair of posterior left ventricular aneurysm.

J Card Surg 2020 Dec 1;35(12):3564-3566. Epub 2020 Oct 1.

Department of CardioVascular Surgery, Cardiac Surgery and Heart Transplantation Institute, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy.

Left ventricular aneurysms (LVA) are a complication of myocardial infarction, that rarely involve the posterior wall; surgical repair of posterior LVA poses a technical challenge when associated with concomitant mitral regurgitation. We describe a minimally invasive treatment of ischemic MR and concomitant patch exclusion of posterior LVA through a right minithoracotomy. Using a transatrial approach, the aneurysm is closed with a "U" shaped dacron patch, whose base is anchored to the mitral annulus. Two patients were operated by this method with excellent results.
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http://dx.doi.org/10.1111/jocs.15059DOI Listing
December 2020

Evaluation of bovine sperm telomere length and association with semen quality.

Theriogenology 2020 Dec 15;158:227-232. Epub 2020 Sep 15.

Department of Veterinary Medicine and Animal Production, Federico II University of Naples, Via F. Delpino 1, 80137, Naples, Italy.

The study aimed to evaluate if the sperm telomere length can be considered as a new biomarker for sperm quality in bulls. Sperm Telomere Length was evaluated by Monochrome Multiplex Quantitative PCR in group A (n = 8) and group B (n = 8) bulls, classified according to standard semen analysis. Also, this parameter was measured before and after Percoll gradient separation within bulls that produced semen of satisfactory quality. Sperm telomere length, measured as T/S ratio (average ratio of telomere repeats copy number to a single copy gene), was higher in group A than in group B bulls (0.77 ± 0.03 vs 0.43 ± 0.06; P < 0.01). Sperm telomere length was positively correlated with motility, viability and membrane integrity, and it was negatively correlated with sperm anomalies. Furthermore, Percoll gradient selected sperms with higher T/S ratio than unselected sperms (1.19 ± 0.02 vs 0.67 ± 0.03). These results suggest that sperm telomere length can be used as a new marker of bovine semen quality.
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http://dx.doi.org/10.1016/j.theriogenology.2020.09.019DOI Listing
December 2020

Appropriateness of magnetic resonance angiography in the evaluation of migraine patients.

Neurol Sci 2020 12;41(Suppl 2):451-452

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, USA.

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http://dx.doi.org/10.1007/s10072-020-04655-4DOI Listing
December 2020

B-Mode and Contrast Enhanced Ultrasonography Features of Gastric Inflammatory and Neoplastic Diseases in Cats.

Animals (Basel) 2020 Aug 18;10(8). Epub 2020 Aug 18.

Faculty of Veterinary Medicine, University of Teramo, SP 18, 64100 Teramo, Italy.

Alimentary lymphoma (AL) is the most common malignancy of the feline gastrointestinal tract and may cause variable mild to severe alteration of the gastric wall on ultrasonography (US) that can be very similar to those caused by inflammation (INF). The aim of this prospective study is to establish the value of B-mode and contrast-enhanced US (CEUS) in describing specific features of normal, inflammatory, and neoplastic gastric diseases in feline species. B-mode US and CEUS of the stomach were performed in anesthetized cats with or without gastric disorders. Gastric wall qualitative and quantitative parameters were evaluated on B-mode US and CEUS examination. A total of 29 cats were included: six healthy (HEA) cats as the control group; nine INF; three low-grade lymphoma (LGAL); 10 high-grade lymphoma (HGAL). On B-mode US, there were significant differences in thickness, the wall's layer definition and echogenicity between HGAL and all the other groups (<0.001). For CEUS, statistical differences between groups were found in the following: HGAL vs. HEA, HGAL vs. INF; HGAL vs. LGAL; INF vs. HEA. Diagnostic accuracy (AUC) and cut-off value were calculated and found to be significant for thickness (3.8 mm) for INF vs. LGAL (AUC > 0.70) and "benign" vs. "malignant" (AUC > 0.90) as well as peak enhancement (34.87 dB) for "benign" vs. "malignant" (AUC > 0.70). INF and LGAL showed an overlap of qualitative and quantitative parameters both on B-mode and CEUS, while HGAL usually appears as a severe wall thickening with absent layer definition, high-contrast uptake, a specific enhancement pattern, regional lymphadenopathy and local steatitis. Thickness and peak enhancement can be useful parameters in the characterization of gastric infiltrates in cats.
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http://dx.doi.org/10.3390/ani10081444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460435PMC
August 2020

The Pro12Ala polymorphism of PPARγ2 modulates beta cell function and failure to oral glucose-lowering drugs in patients with type 2 diabetes.

Diabetes Metab Res Rev 2021 Mar 2;37(3):e3392. Epub 2020 Sep 2.

Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.

Background: We evaluate whether the Pro12Ala polymorphism of peroxisome proliferator-activated receptor γ2 (PPARγ2) has a role in the progression of diabetes by modulating the occurrence of treatment failure to glucose-lowering drugs.

Methods: We studied 215 patients with type 2 diabetes participating in the Thiazolidinediones Or Sulphonylureas and Cardiovascular Accidents Intervention Trial study. All participants were insufficiently controlled (glycated haemoglobin [HbA ] 7.0%-9.0%) with metformin 2 g/day and were randomly allocated to add-on pioglitazone or a sulfonylurea. Treatment failure was defined as HbA ≥8% on two consecutive visits, 3 months apart.

Results: Carriers or non-carriers of the polymorphism had similar age, body mass index, and diabetes duration. Ala carriers had lower fasting plasma insulin, better insulin sensitivity (Homeostasis Model Assessment [HOMA]2-%S), and worse beta cell secretion (HOMA2-%B) than non-carriers. During 24 months of follow-up, 32.5% among the Ala carriers and 8.6% among non-carriers (P < 0.001) developed treatment failure with a cumulative incidence of 18.6 vs 4.6/100 person-years. Those patients who developed treatment failure were older, had a younger age at diabetes diagnosis (48 ± 10 vs 52 ± 7 years; P = 0.032), higher HbA (8.1 ± 0.5 vs 7.7 ± 0.5%; P < 0.001), and lower HOMA2-%B (30 ± 12 vs 46 ± 29; P = 0.015) at study entry, as compared to those who did not develop treatment failure. At multivariate analysis, the Pro12Ala polymorphism was significantly associated with treatment failure (hazard ratio [HR] 4.45; 95% confidence interval [CI] 1.79-11.1; P < 0.001); HbA at study entry was the other independent predictor of failure in this study population.

Conclusion: The Pro12Ala polymorphism is associated with a greater insulin sensitivity, reduced beta cell function and a substantially increased risk of treatment failure.
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http://dx.doi.org/10.1002/dmrr.3392DOI Listing
March 2021

Seasonal effects on miRNA and transcriptomic profile of oocytes and follicular cells in buffalo (Bubalus bubalis).

Sci Rep 2020 08 11;10(1):13557. Epub 2020 Aug 11.

Dipartimento di Medicina Veterinaria e Produzioni Animali (DMVPA), Università Degli Studi di Napoli Federico II, Via F. Delpino 1, 80137, Naples, Italy.

Season clearly influences oocyte competence in buffalo (Bubalus bubalis); however, changes in the oocyte molecular status in relation to season are poorly understood. This study characterizes the microRNA (miRNA) and transcriptomic profiles of oocytes (OOs) and corresponding follicular cells (FCs) from buffalo ovaries collected in the breeding (BS) and non-breeding (NBS) seasons. In the BS, cleavage and blastocyst rates are significantly higher compared to NBS. Thirteen miRNAs and two mRNAs showed differential expression (DE) in FCs between BS and NBS. DE-miRNAs target gene analysis uncovered pathways associated with transforming growth factor β (TGFβ) and circadian clock photoperiod. Oocytes cluster in function of season for their miRNA content, showing 13 DE-miRNAs between BS and NBS. Between the two seasons, 22 differentially expressed genes were also observed. Gene Ontology (GO) analysis of miRNA target genes and differentially expressed genes (DEGs) in OOs highlights pathways related to triglyceride and sterol biosynthesis and storage. Co-expression analysis of miRNAs and mRNAs revealed a positive correlation between miR-296-3p and genes related to metabolism and hormone regulation. In conclusion, season significantly affects female fertility in buffalo and impacts on oocyte transcriptomic of genes related to folliculogenesis and acquisition of oocyte competence.
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http://dx.doi.org/10.1038/s41598-020-70546-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419291PMC
August 2020
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