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Thus, we examined the umbilical artery (UA) and middle cerebral artery (MCA) Doppler in appropriate for gestational age (AGA) fetuses of healthy and HDP pregnancies at 32 weeks. Hypertensive disorders of pregnancy (HDP) include gestational hypertension (GH), chronic hypertension (CH) and pre-eclampsia (PE). [Extracted from the article]

Cell-free fetal DNA (cffDNA) testing represents the best screening method for common aneuploidies. Conclusions In conclusion, our results highlighted the importance of an adequate counselling to pregnant women with high BMI regarding the test reliability and its clinical implications. [Extracted from the article]

Conclusions In conclusion, our study shows that low serum PAPP-A levels in the first trimester were strongly associated with an increased risk of pregnancy complications. EP01.42: First trimester screening: the increasing value of adding serum PAPP-A levels in predicting pregnancy outcomes The aim of this study is to investigate the ability of first trimester maternal serum pregnancy associated plasma protein A (PAPP-A) in the prediction of pregnancy complications. [Extracted from the article]

The cell density and incorporation of 35SO4 and 3H-glycine into human articular cartilage from 8 osteoarthrotic and 7 normal (subcapital fracture) femoral heads were studied. It was found that osteoarthrotic cartilage incorporates on a per cell basis about twice as much 35SO4 and 2--5 times as much 3H-glycine as normal cartilage. There was no relationship between the intensity of incorporation and either the location of the cartilage (weight-bearing versus non weight-bearing areas) in normal cartilage or the degree of damage (normal-like, fibrillated, and ulcerated) in osteoarthrotic articular cartilage. In the latter tissue the increased synthetic capacity of the cells seems to be a diffuse rather than a localised process, for it was also found in cartilage from peripheral osteophytes. Histo-autoradiographic studies showed that the osteoarthrotic chondrocytes are metabolically hyperactive all over the femoral head, including wedge-shaped margins of the zone of exposed bone. These results support the hypothesis that much of the articular cartilage from osteoarthrotic femoral heads is of an immature chondroblastic type. It is suggested that de-novo synthesis of articular cartilage occurs during the process of regional remodelling of the femoral head, which would account for the observed hyperactivity. [ABSTRACT FROM AUTHOR]

The primary intervention for pre-eclampsia (PE) remains iatrogenic delivery, which can be very preterm and not optimal for the fetus. Although many efforts have been made to prevent and manage PE, there is still a dearth of drugs to treat its pathophysiological progression. Pravastatin (PRA), a hydrophilic statin, has gained interest for the prevention and treatment of PE. The aim of the present study was to evaluate the ability of PRA to modulate factors involved in placentation, such as Epidermal Growth Factor-Like Domain 7 (EGFL7), in human chorionic villous culture from healthy controls and women with PE. A total of 18 women were enrolled: 10 controls and 8 cases. Chorionic villous explants were maintained in culture for 24 h with or without 10 μM Pravastatin, and the expression of EGFL7 and NOTCH1 pathway members was evaluated by qRT-PCR and Western blot analysis. The rationale of the present study was to establish an ex vivo model to identify potential different responses to PRA treatment of chorionic villous explants in order to clarify the molecular mechanism of PRA in the prevention and treatment of PE and to predict whether there are specific clinical conditions that modulate the response to the drug treatment. Within PE patients, two different groups were identified: the high responders, whose villous cultures exhibit significantly increased expressions of the EGFL7 and Notch pathways after PRA incubation; and the low responders, who are high-risk PE patients in which prophylaxis failed to prevent PE and PRA was not able to modulate EGFL7 expression. In conclusion, we identified EGFL7 as a new factor regulated by PRA, placing interest in early discrimination between low- and high- risk women, in which the well-known pharmacological prophylaxis seems to be ineffective, and to explore new potential prevention strategies.

Competing Interests: The authors declare that they have no conflict of interest.

Purposes: To investigate the effects for Ultra 3D cochlear implant (CI) positioning on MR imaging quality, looking at a comprehensive description of intracranial structures in cases of unilateral and bilateral CI placement., Methods: Four CI angular positions (90°, 120°, 135° and 160°) at 9 cm distance from the outer-ear canal were explored. The 1.5 T MRI assessment included our institutional protocol for the investigation of brain pathologies without gadolinium application. Three investigators (two experienced neuroradiologists and one experienced otoneurosurgeon) independently evaluated the MR findings. A 4-point scale was adopted to describe 14 intracranial structures and to determine which CI positioning allowed the best image quality score and how bilateral CI placement modified MRI scan visibility., Results: A high positive correlation was found between the three blinded observers. Structures situated contralateral from the CI showed high-quality values in all four placements. Structures situated ipsilaterally provided results suitable for diagnostic purposes for at least one position. At 90°, artifacts mainly involved brain structures located cranially and anteriorly (e.g., temporal lobe); on the contrary, at 160°, artifacts mostly influenced the posterior fossa structures (e.g., occipital lobe). For the bilateral CI condition, MR imaging examination revealed additional artifacts involving all structures located close to either CI, where there was a signal void/distortion area., Conclusions: Suitable unilateral CI positioning can allow the visualization of intracranial structures with sufficient visibility for diagnostic purposes. Bilateral CI positioning significantly deteriorates the anatomical visibility. CI positioning might play a crucial role for patients who need post-operative MRI surveillance., (© 2021. The Author(s).)

Purpose: Coronavirus infection disease 2019 (COVID-19) causes in 10% of patients a severe respiratory distress syndrome managed with invasive mechanical ventilation (IMV), sometimes difficult to wean. The role of tracheotomy is debated for the possible risks for patients and staff. We are going to describe here our experience with surgical tracheotomy in COVID-19 positive patients., Methods: We enrolled all intensive care unit (ICU) patients requiring longer than 10 days of IMV. Demographic, clinical, respiratory, complications, and outcomes data were collected, in a particular length of weaning from sedation and IMV, in-ICU and in-hospital mortality rate. All healthcare operators involved were tested for SARS-CoV2 by pharyngeal swab and blood test (antibody test)., Results: 13 out of 68 ICU patients (19.1%) underwent surgical tracheotomy after a median intubation period of 14 days. The mean age was 60 (56-65) years. 85% were male patients. Postoperative mild bleeding was seen in 30.7%, pneumothorax in 7.7%. Mean weaning from sedation required 3 days, 19 days from IMV. In-ICU and in-hospital COVID-infection-related mortality was 23.1% and 30.7%, respectively. None of the healthcare operators was found SARS-CoV2 positive during the period of the study., Conclusions: In COVID-19 pandemic surgical tracheotomy enables to wean from sedation and subsequently from IMV in a safe way for both patients and personnel., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Purposes: To primarily evaluate MRI-induced effects for Ultra 3D cochlear implantation in human cadavers in terms of artifact generation and MR image quality., Methods: Three human cadaveric heads were submitted to imaging after unilateral and bilateral cochlear implantation. The 1.5 T MR examination protocol was chosen in accordance with our institutional protocol for the assessment of brain pathology. The maximal signal void size was measured according to each sequence and plane. Two experienced neuro-radiologists and one experienced otoneurosurgeon independently evaluated the MR image quality findings. A 4-point scale was used to describe the diagnostic usefulness of 14 brain structures., Results: Shape and size of the artifacts were found to be highly related to MRI sequences and acquisition planes. MRI sequences and processing algorithms affected the ability to assess anatomical visibility. Image quality appeared either high or assessable for diagnostic purposes in 9 out of 14 of the ipsilateral structures, in at least one plane. Anatomical structures contralateral to the cochlear implant were highly visible in all conditions. Artifact intrusion clearly improved after application of metal artifact-reduction techniques. In the case of bilateral cochlear implant, a mutual interaction between the two implant magnets produced an additional artifact., Conclusions: We performed the first cadaver study aimed at systematically evaluating the MRI-induced artifacts produced by a cochlear implant with a novel four bar magnet system. Specific brain structures can be assessable for diagnostic purposes under 1.5 T MRI, with the cochlear implant magnet in place., (© 2020. The Author(s).)

Gut microbiota plays an important role in human health. It may promote carcinogenesis and is related to several diseases of the gastrointestinal tract. This study of microbial dysbiosis in the etiology of colorectal adenoma aimed to investigate the possible causative role of microbiota in the adenoma-carcinoma sequence and its possible preventive role. A systematic, PRISMA-guided review was performed. The PubMed database was searched using "adenoma microbiota" and selecting original articles between January 2010 and May 2020 independently screened. A higher prevalence of Proteobacteria, Fusobacteria, and Bacteroidetes phyla was observed in the fecal luminal and mucosa-associated microbiota of patients with adenoma. However, other studies provided evidence of depletion of Clostridium , Faecalibacterium , Bacteroides and Romboutsia . Results on the relationship between adenoma endoscopic resection and microbiota were inconsistent. In conclusion, none of the analyzed studies developed a predictive model that could differentiate adenoma from non-adenoma patients, and therefore, to prevent cancer progression. The impact of adenoma's endoscopic resection on microbiota was investigated, but the results were inconclusive. Further research in the field is required.

Background Cirrhosis leads to portal hypertension and to the consequent formation of spontaneous portosystemic shunts (SPSSs), leading to complications related to the diversion of portal blood into the systemic circulation, which is called portosystemic shunt syndrome. Purpose To investigate the characteristics of patients with cirrhosis and an SPSS and secondarily to assess the prognostic impact of SPSSs on portal hypertension-related complications and transplant-free survival. Materials and Methods A retrospective database review of patients with cirrhosis (observed from March 2015 to July 2019) was performed to identify patients with CT imaging and outcomes data. For each patient, clinical and biochemical data were collected, and the presence, types, and sizes of SPSSs were investigated with CT. Patients were followed for a mean of 27.5 months ± 22.8. Multivariable logistic analysis was used to identify the clinical characteristics associated with the presence of SPSSs (any size) and presence of SPSSs 1 cm or larger. Competitive risk analysis (Fine and Gray model) was used to identify the association between SPSSs and complications and mortality. Results Two hundred twenty-two patients with cirrhosis (157 male, 65 female; mean age, 62 years ± 12 [standard deviation]) were evaluated. An SPSS was found in 141 of 222 patients (63.5%), and 40 of 222 (18%) had a shunt diameter of at least 1 cm. At presentation, variables independently associated with the presence of SPSSs (any size) were portal vein thrombosis (odds ratio, 5.5; P = .008) and Child-Pugh class C (odds ratio, 3.0; P = .03). Previous hepatic encephalopathy (odds ratio, 4.4; P = .001) and portal vein thrombosis (odds ratio, 5.3; P = .001) were the only variables associated with SPSSs larger than 1 cm. Patients with SPSSs of any size had higher mortality (subdistribution hazard ratio, 1.9; P < .001) and higher frequency of hepatic encephalopathy (subdistribution hazard ratio, 2.3; P = .023), gastrointestinal bleeding (subdistribution hazard ratio, 2.9; P = .039), and portal vein thrombosis (subdistribution hazard ratio, 7.6; P = .005). Conclusion The presence of spontaneous portosystemic shunts on CT images in patients with cirrhosis was associated with higher mortality and complications, including portal vein thrombosis, hepatic encephalopathy, and gastrointestinal bleeding. © RSNA, 2021 See also the editorial by Reeder in this issue.

Copper resistance mechanisms provide an important adaptive advantage to plant pathogenic bacteria under exposure to copper treatments. Copper resistance determinants have been described in Pseudomonas syringae pv. syringae (Pss) strains isolated from mango intimately associated with 62 kb plasmids belonging to the pPT23A family (PFP). It has been previously described that the indiscriminate use of copper-based compounds promotes the selection of copper resistant bacterial strains and constitutes a selective pressure in the evolution of copper resistance determinants. Hence, we have explored in this study the copper resistance evolution and the distribution of specific genetic determinants in two different Pss mango populations isolated from the same geographical regions, mainly from southern Spain with an average of 20 years of difference. The total content of plasmids, in particular the 62 kb plasmids, and the number of copper resistant Pss strains were maintained at similar levels over the time. Interestingly, the phylogenetic analysis indicated the presence of a phylogenetic subgroup (PSG) in the Pss mango phylotype, mostly composed of the recent Pss population analyzed in this study that was strongly associated with a hyper-resistant phenotype to copper. Genome sequencing of two selected Pss strains from this PSG revealed the presence of a large Tn7-like transposon of chromosomal location, which harbored putative copper and arsenic resistance genes (COARS Tn7-like). Transformation of the copper sensitive Pss UMAF0158 strain with some putative copper resistance genes and RT-qPCR experiments brought into light the role of COARS Tn7-like transposon in the hyper-resistant phenotype to copper in Pss. IMPORTANCE Copper compounds have traditionally been used as standard bactericides in agriculture in the past few decades. However, the extensive use of copper has fostered the evolution of bacterial copper resistance mechanisms. Pseudomonas syringae is a plant pathogenic bacterium used worldwide as a model to study plant-pathogen interactions. The adaption of P. syringae to plant surface environment is the most important step prior to an infection. In this scenario, copper resistance mechanisms could play a key role in improving its epiphytic survival. In this work, a novel Tn7-like transposon of chromosomal location was detected in P. syringae pv. syringae strains isolated from mango. This transposon conferred the highest resistance to copper sulfate described to date for this bacterial phytopathogen. Understanding in depth the copper resistance mechanisms and their evolution are important steps to the agricultural industry to get a better improvement of disease management strategies., (Copyright © 2020 American Society for Microbiology.)

Introduction: The retrosigmoidal (RS) placement of the Bonebridge system (BB) has been advocated for cases of unfavourable anatomical or clinical conditions which contraindicate transmastoid-presigmoidal positioning. However, these disadvantageous conditions, combined with the considerable dimensions of the implant, may represent a challenge, especially for surgeons with no skull base experience. Moreover, the literature reports only limited experience concerning RS implantation of the BB system., Methods: A multicentre, retrospective study was conducted to analyse the surgical and functional outcomes of a wide population of patients undergoing RS placement of the BB system by means of a surgical technique specifically developed to overcome the intraoperative issues related to this surgery. Twenty patients with conductive or mixed hearing loss and single sided deafness were submitted to RS implantation of the BB system., Results: Audiological assessment concerning the measurement of the functional and effective gain by pure-tone audiometry (28 dB HL and -12.25 dB HL, respectively) and speech audiometry (24.7 dB HL and -21 dB HL, respectively) was conducted. A high overall subjective improvement of quality of life was recorded with the Glasgow Benefit Inventory questionnaire. No major complications, such as device extrusions or other conditions requiring revision surgery, were reported during the follow-up period (median: 42 months)., Conclusions: In our study, which has one of the largest cohort of patients reported in the literature, RS placement of the BB system was safe and effective. Our functional results showed comparable hearing outcomes with presigmoidal placement. The effective gain, rarely investigated in this field, may be the object of further research to improve our understanding of bone conduction mechanisms exploited by bone conduction hearing implants., (Copyright © 2021 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

This review explores the latest guidelines on nutrition in patients with chronic liver diseases of the European Association for the Study of the Liver (EASL) and recent studies on physiopathology, clinical outcomes and possible treatments of malnutrition and sarcopenia in liver cirrhosis. Chronic liver diseases are frequently associated with malnutrition, changes in skeletal muscle and bone quality and quantity. About 20% of patients with compensated liver cirrhosis and 50% of those with decompensated cirrhosis are sarcopenic. Malnutrition and sarcopenia are associated with a higher complication rate (ascites, bacterial infections and hepatic encephalopathy) and are independent predictors of lower survival in cirrhotic patients. In recent years, concomitant with the decline of post-viral cirrhosis, patients affected by post-metabolic cirrhosis are increasing. These patients are more frequently overweight or obese, but sarcopenia may also coexist. Sarcopenic obesity has been shown to worsen the prognosis in patients with liver cirrhosis. There is a general consensus about the need of improving the nutritional status and implementing skeletal muscle mass in cirrhotic patients, but this is not always achievable. Osteoporosis is present in about 30% of cirrhotic patients, with a higher prevalence in patients with cholestasis. Treatment with phosphonates, calcium and vitamin D are recommended in association with a periodic follow-up.

Background: Splanchnic vein thrombosis (SVT) is an uncommon but potentially life-threatening disease usually related to different underlying clinical conditions. The risk of SVT recurrences is high over time in patients with an underlying permanent prothrombotic condition. Vitamin K antagonists (VKA) represent the mainstay of treatment for SVT. Data about the efficacy and safety of direct oral anticoagulants (DOACs) are reported in the literature for the treatment of acute SVT, but less is known about their application for the secondary prophylaxis of venous thromboembolism (VTE). The aim of this study was to assess the efficacy and safety of long-term DOACs therapy in patients at high-risk of thrombosis, compared to VKA., Methods: This is a retrospective single-centre study including 70 patients with SVT on long-term anticoagulant treatment with VKA followed-up at our Units between January 2017 and December 2019. All the patients were at high thrombotic risk defined as the presence of a permanent prothrombotic condition requiring long-term anticoagulation. During follow-up, 28 patients were shifted to DOACs and their clinical outcomes were compared to those of the patients who continued VKA therapy. All the arterial and venous thrombotic events of the splanchnic and extra-splanchnic districts as well as the haemorrhagic adverse events occurring during follow-up were recorded., Results: Of the seventy patients enrolled in the study, 36 patients (51.4%) had a single-segment involvement thrombosis (28.5% of portal vein, 7.1% of superior mesenteric vein, 4.3% of splenic vein, 11.5% of hepatic veins) and 34 patients (48.6%) had multi-segment involvement at the time of diagnosis. 42 patients (60%) continued VKA therapy and 28 (40%) were switched to DOACs. Median follow-up was 6 years (range 2-8) during VKA and 1.9 years (range 1-5.2) during DOACs. The incidence of thrombotic events was similar between patients on VKA and those on DOACs. Patients on VKA developed deep vein thrombosis (DVT), and of the patients on DOACs 1 developed NSTEMI and 1 DVT. No major haemorrhagic events occurred. Minor bleedings occurred in 26% of patients on VKA and in none of the DOACs patients (P: 0.09)., Conclusions: Our results highlight that DOACs could represent an effective and safe alternative to the VKA for secondary prophylaxis in SVT patients at high risk of thrombosis., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: The electrocardiographic (ECG) definition of Brugada syndrome (BS) can be challenging because benign ECG abnormalities, such as right bundle branch block (RBBB), may mimic pathological ECG characteristics of BrS. However, although myocardial delay and deformation can be quantified by advanced imaging, it has not yet been used to differentiate between BrS and RBBB. The aim of this study was to characterize the electro-mechanical behavior of the heart of patients with type-1 BrS and isolated complete RBBB in order to differentiate these conditions., Methods: In this two-center study, 66 subjects were analyzed by standard and speckle-tracking echocardiography (STE): 22 type-1 BrS, 24 isolated complete RBBB, and 20 healthy subjects. The participants were not treated by any drug potentially influencing myocardial conduction., Results: Standard echocardiographic parameters did not differ among the groups. The greatest right ventricular (RV) mechanical dispersion was found in RBBB. Mean absolute deviations (MADs) of time-to-peak longitudinal strain calculated for each left ventricular (LV) region were greater in patients with RBBB as compared to BrS (p < .01). No differences were found between BrS and controls (p = .36). MADs in the basal segments in RBBB group were greater than MADs found in BrS group and controls (37.3 ms vs. 26.7 ms and 29.0 ms, respectively, p < .05). The greatest differences were found in the antero-septal, anterior, lateral, and infero-septal basal segments., Conclusions: Advanced echocardiographic techniques may help to differentiate between BrS and RBBB. Indeed, STE allows to identify an electro-mechanical conduction delay in RBBB patients that is not found in patients affected by type-1 BrS., Competing Interests: Declaration of Competing Interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purposes: To explore the feasibility of 3D printed salivary duct models for the sialendoscopic skills training., Methods: Healthy volunteers and patients affected by obstructive salivary gland disorders were submitted to 3 Tesla MR sialography. The MR data underwent an image segmentation process to produce the 3D printed salivary duct prototypes. Sialendoscopies were carried out by three groups of investigators with different levels of endoscopic experience. Realism, usefulness of the training process and potential advantages of the 3D printed models in the preoperative surgical planning were evaluated by means of a specific survey., Results: Four cases were included in our study: one healthy parotid, one submandibular gland, one case of lithiasis and one of stenosis involving the parotid gland. In all cases, the three groups of investigators successfully explored the salivary ducts up to the tertiary branches, detected the cause of obstruction and correctly treated it. Seven untoward events occurred during the operative sialendoscopies. Overall, the questionnaire score was about 79.3%, reflecting a positive impression regarding the models on behalf of all the investigators., Conclusions: 3D printed salivary duct models resulted feasible for the sialendoscopic skills training. The opportunity to reproduce the patient-specific anatomy may add further information useful in the preoperative decision making. These positive results should be verified by further researches and experiences.

Background: Some concerns exist about possible detrimental effects on cardiac function of ultra-endurance competitions. The aim of this study was to evaluate the acute effects of an ultramarathon by comparing pre- and post-race 12-lead ECG features., Methods: A total of 301 competitive athletes (mean age: 48 ± 9 years) running a 50-km ultramarathon were analyzed. Twelve-lead ECG was collected the day before the race and immediately at the finish line. According to the Italian law, athletes could have participated only after undergoing pre-participation screening that ruled out the presence of an underlying heart disease., Results: After the race a significant increase in P-wave voltage (P < .001) and P-wave duration (P < .001) was found as compared to pre-race data with a higher percentage of athletes fulfilling the ECG criteria for right atrial enlargement (RAE; from 3% to 17%, P < .001). The presence of RAE post-race significantly correlated with age, hours of training/week, and years of training and inversely with time at the finish line and the final position in the ranking. T-wave and R-wave amplitude (P < .001) and QTc-interval duration (P < .001) significantly increased after the race. No significant differences in terms of supraventricular or ventricular arrhythmias were found., Conclusions: A sizeable proportion of athletes running a 50-km ultramarathon demonstrated post-race ECG signs of right heart overload but no arrhythmias. This finding supports the hypothesis that ultra-endurance races may induce transient right heart overload., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)