Higher testosterone is associated with increased inflammatory markers in women with SARS-CoV-2 pneumonia: preliminary results from an observational study.

PURPOSE: Objective of this study was to assess the association between testosterone (T) levels and biochemical markers in a cohort of female patients admitted for SARS-CoV-2 infection in a respiratory intensive care unit (RICU). METHODS: A consecutive series of 17 women affected by SARSCoV-2 pneumonia and recovered in the RICU of the Hospital of Mantua were analyzed. Biochemical inflammatory markers as well as total testosterone (TT), calculated free T (cFT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were determined. RESULTS: TT and cFT were significantly and positively associated with PCT, CRP, and fibrinogen as well as with a worse hospital course. We did not observe any significant association between TT and cFT with LH; conversely, both TT and cFT showed a positive correlation with cortisol. By LOWESS analysis, a linear relationship could be assumed for CRP and fibrinogen, while a threshold effect was apparent in the relationship between TT and procalcitonin, LDH and ferritin. When the TT threshold value of 1 nmol/L was used, significant associations between TT and PCT, LDH or ferritin were observed for values above this value. For LDH and ferritin, this was confirmed also in an age-adjusted model. Similar results were found for the association of cFT with the inflammatory markers with a threshold effect towards LDH and ferritin with increased LDH and ferritin levels for values above cFT 5 pmol/L. Cortisol is associated with serum inflammatory markers with similar trends observed for TT; conversely, the relationship between LH and inflammatory markers had different trends. CONCLUSION: Opposite to men, in women with SARS-CoV-2 pneumonia, higher TT and cFT are associated with a stronger inflammatory status, probably related to adrenal cortex hyperactivity.

Mechanical hysteroscopic tissue removal or hysteroscopic morcellator: understanding the past to predict the future. A narrative review.

BACKGROUND: In recent years, the available evidence revealed that mechanical hysteroscopic tissue removal (mHTR) systems represent a safe and effective alternative to conventional operative resectoscopic hysteroscopy to treat a diverse spectrum of intrauterine pathology including endometrial polyps, uterine myomas, removal of placental remnants and to perform targeted endometrial biopsy under direct visualisation. This innovative technology simultaneously cuts and removes the tissue, allowing one to perform the procedure in a safer, faster and more effective way compared to conventional resectoscopic surgery. OBJECTIVE: To review currently available scientific evidence concerning the use of mechanical hysteroscopic morcellators and highlight relevant aspects of the technology. MATERIAL AND METHODS: A narrative review was conducted analysing the available literature regarding hysteroscopic tissue removal systems. MAIN OUTCOME MEASURES: Characteristics of available mHTR systems, procedures they are used for, their performance including safety aspects and their comparison. RESULTS: A total of 7 hysteroscopic morcellators were identified. The diameter of the external sheet ranged from 5.25 to 9.0 mm, optics ranged from 0.8 to 6.3 mm with 0o angle. The cutter device diameter ranged from 2.9 to 4.5 mm most of them with rotation and reciprocation. CONCLUSION: We conclude that the adoption of mHTR has shown to reduce operating time, simultaneously cutting and suctioning tissue fragments avoiding the need for multiple removal and reinsertions of the device into the uterine cavity as well as reducing the volume of distension media required to complete the procedure compared to using the hysteroscopic resectoscope.

Mortality from COVID-19.

Abstract: The differences of the epidemiology (incidence, case-to-death rate, mortality, etc) of COVID-19 between USA and Italy are analyzed taking into account the social, economic and sanitary characteristics of the two countries, both severely hit be the pandemic; and the causes of the so many different behaviors of the disease in each of them are discussed and explained.

The impact of social complexity on the visual exploration of others' actions in preschoolers with autism spectrum disorder.

BACKGROUND: Typical development of socio-communicative skills relies on keen observation of others. It thus follows that decreased social attention negatively impacts the subsequent development of socio-communicative abilities in children with autism spectrum disorders (ASD). In addition, studies indicate that social attention is modulated by context and that greater social difficulties are observed in more socially demanding situations. Our study aims to investigate the effect of social complexity on visual exploration of others' actions in preschoolers. METHODS: To investigate the impact of social complexity, we used an eye-tracking paradigm with 26 typically developing preschoolers (TD, age = 3.60 ± 1.55) and 37 preschoolers with ASD (age = 3.55 ± 1.21). Participants were shown videos of two children engaging in socially simple play (parallel) versus socially complex play (interactive). We subsequently quantified the time spent and fixation duration on faces, objects, bodies, as well as the background and the number of spontaneous gaze shifts between socially relevant areas of interest. RESULTS: In the ASD group, we observed decreased time spent on faces. Social complexity (interactive play) elicited changes in visual exploration patterns in both groups. From the parallel to the interactive condition, we observed a shift towards socially relevant parts of the scene, a decrease in fixation duration, as well as an increase in spontaneous gaze shifts between faces and objects though there were fewer in the ASD group. LIMITATIONS: Our results need to be interpreted cautiously due to relatively small sample sizes and may be relevant to male preschoolers, given our male-only sample and reported phenotypic differences between males and females. CONCLUSION: Our results suggest that similar to TD children, though to a lesser extent, visual exploration patterns in ASD are modulated by context. Children with ASD that were less sensitive to context modulation showed decreased socio-communicative skills or higher levels of symptoms. Our findings support using naturalistic designs to capture socio-communicative deficits in ASD.

Impact of pathogen-reduction technologies on COVID-19 convalescent plasma potency.

Pathogen reduction technologies (PRT) have been recommended by many regulatory authorities to minimize the residual risk of transfusion-transmitted infections associated with COVID19 convalescent plasma. While its impact on safety and its cost-effectiveness are nowadays well proven, there is theoretical concern that PRT could impact efficacy of convalescent plasma by altering concentration and/or function of the neutralizing antibodies (nAb). We review here the evidence supporting a lack of significant detrimental effect from PRTs on nAbs.

Sensitization to Gibberellin-Regulated Protein (Peamaclein) Among Italian Cypress Pollen-Sensitized Patients.

BACKGROUND AND OBJECTIVES: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen-allergic patients. MATERIAL AND METHODS: A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. RESULTS: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. CONCLUSION: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

Patient blood management during the COVID-19 pandemic: a narrative review.

As COVID-19 disease escalates globally, optimising patient outcome during this catastrophic healthcare crisis is the number one priority. The principles of patient blood management are fundamental strategies to improve patient outcomes and should be given high priority in this crisis situation. The aim of this expert review is to provide clinicians and healthcare authorities with information regarding how to apply established principles of patient blood management during the COVID-19 pandemic. In particular, this review considers the impact of the COVID-19 pandemic on blood supply and specifies important aspects of donor management. We discuss how preventative and control measures implemented during the COVID-19 crisis could affect the prevalence of anaemia, and highlight issues regarding the diagnosis and treatment of anaemia in patients requiring elective or emergency surgery. In addition, we review aspects related to patient blood management of critically ill patients with known or suspected COVID-19, and discuss important alterations of the coagulation system in patients hospitalised due to COVID-19. Finally, we address special considerations pertaining to supply-demand and cost-benefit issues of patient blood management during the COVID-19 pandemic.

Variability in Verbal and Nonverbal Communication in Infants at Risk for Autism Spectrum Disorder: Predictors and Outcomes.

Early communication impairment is among the most-reported first concerns in parents of young children with autism spectrum disorder (ASD). Using a parent-report questionnaire, we derived trajectory groups for early language and gesture acquisition in siblings at high risk for ASD and in children at low risk, during their first 2 years of life. Developmental skills at 6 months were associated with trajectory group membership representing growth in receptive language and gestures. Behavioral symptoms also predicted gesture development. All communication measures were strongly related to clinical and developmental outcomes. Trajectory groups further indicated slowest language/gesture acquisition in infants with later ASD diagnoses, in particular when associated with language delay. Overall, our results confirm considerable variability in communication development in high-risk infants.

First nationwide antimicrobial susceptibility surveillance for Neisseria gonorrhoeae in Brazil, 2015-16.

Objectives: Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are major public health concerns globally. Enhanced AMR surveillance for gonococci is essential worldwide; however, recent quality-assured gonococcal AMR surveillance in Latin America, including Brazil, has been limited. Our aims were to (i) establish the first nationwide gonococcal AMR surveillance, quality assured according to WHO standards, in Brazil, and (ii) describe the antimicrobial susceptibility of clinical gonococcal isolates collected from 2015 to 2016 in all five main regions (seven sentinel sites) of Brazil. Methods: Gonococcal isolates from 550 men with urethral discharge were examined for susceptibility to ceftriaxone, cefixime, azithromycin, ciprofloxacin, benzylpenicillin and tetracycline using the agar dilution method, according to CLSI recommendations and quality assured according to WHO standards. Results: The levels of resistance (intermediate susceptibility) to tetracycline, ciprofloxacin, benzylpenicillin and azithromycin were 61.6% (34.2%), 55.6% (0.5%), 37.1% (60.4%) and 6.9% (8.9%), respectively. All isolates were susceptible to ceftriaxone and cefixime using the US CLSI breakpoints. However, according to the European EUCAST cefixime breakpoints, 0.2% (n = 1) of isolates were cefixime resistant and 6.9% (n = 38) of isolates had a cefixime MIC bordering on resistance. Conclusions: This study describes the first national surveillance of gonococcal AMR in Brazil, which was quality assured according to WHO standards. The high resistance to ciprofloxacin (which promptly informed a revision of the Brazilian sexually transmitted infection treatment guideline), emerging resistance to azithromycin and decreasing susceptibility to extended-spectrum cephalosporins necessitate continuous surveillance of gonococcal AMR and ideally treatment failures, and increased awareness when prescribing treatment in Brazil.

Phosphorescent iridium-containing nanomicelles: synthesis, characterization and preliminary applications in nanomedical imaging.

Diagnostic nanomedicine constantly requires the development of novel contrast agents with intrinsic imaging capabilities. Phosphorescent Ir(iii)-complexes represent good candidates when delivered through polymeric nanoparticles. In this work, we propose a biocompatible nanoparticle made from an intrinsically phosphorescent copolymer, synthesized directly with an imaging tag present on its backbone. Polymeric nanoparticles can be obtained with the exact amount of phosphorescent moieties needed to maximize their output signal. Complete characterization and ex vivo studies confirmed that this nanosystem is suitable as a future diagnostic tool.

One-step transvaginal three-dimensional hysterosalpingo-foam sonography (3D-HyFoSy) confirmation test for Essure® follow-up: a multicenter study.

OBJECTIVE: To evaluate, in patients who underwent Fallopian-tube sterilization by hysteroscopic insertion of an Essure® device, the feasibility and accuracy of three-dimensional (3D) transvaginal sonography (TVS) to check the position of the device and 3D hysterosalpingo-foam sonography (3D-HyFoSy) using contrast-enhanced gel foam to assess consequent tubal occlusion. METHODS: This was a prospective multicenter study conducted from June 2012 to July 2014 in four Italian centers, which included 50 women who underwent hysteroscopic Essure microinsert placement in a total of 95 Fallopian tubes. Placement of the microinserts was performed in an outpatient setting following standard procedure recommendations. All patients underwent transvaginal 3D-HyFoSy and hysterosalpingography (HSG) approximately 12-14 weeks after the procedure. The position of the devices was first checked on 3D-TVS and classified according to specific criteria (Positions A, B, C and D). Then, 3D-HyFoSy with ExEm® gel foam as the ultrasound contrast agent was performed to confirm tubal occlusion by the absence of contrast agent within the tubes and/or around the ovaries. To evaluate the feasibility of 3D-HyFoSy, consecutive volume acquisitions were performed while injecting the gel foam. After sonographic evaluation, women underwent HSG to assess the success of sterilization, as standard methodology. Side effects and pain evoked during and after 3D-HyFoSy and HSG were evaluated using a numeric pain rating scale. RESULTS: On 3D-TVS, 10 devices (10.5%) were in Position A, two (2.1%) in Position B, 59 (62.1%) in Position C and 24 (25.3%) in Position D. During 3D-HyFoSy, tubal occlusion was observed in 89 of 95 tubes (93.7%). In the six cases in which the passage of the contrast was observed, one device (16.7%) was in Position B, one device (16.7%) in Position D and four devices (66.7%) were found to lie in Position C. Tubal patency was confirmed at HSG with a concordance rate of 100%. The mean pain score associated with 3D-HyFoSy was significantly lower than that on HSG. CONCLUSIONS: 3D-TVS with HyFoSy allows accurate assessment of the position of Essure microinserts and tubal occlusion. It can be considered a safe, reliable, non-invasive alternative to HSG. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

The human pegivirus: A new name for an "ancient" virus. Can transfusion medicine come up with something new?

Human pegivirus (HPgV, formerly called GB virus C/hepatitis G virus) is a poorly understood RNA virus of the Flaviviridae family. The HPgV infection is common worldwide and the virus is likely transmitted by blood products. At this time, no causal association between HPgV and human diseases has been identified. While waiting for new findings to better understand the Pegivirus genus, the aim of our narrative review is to discuss the currently available information on HPgV focusing on its prevalence in blood donors and its potential threat to transfusion safety.

Laboratory monitoring of replacement therapy for major surgery in von Willebrand disease.

Von Willebrand disease (VWD) is an inherited haemorrhagic disorder caused by a quantitative or qualitative defect of von Willebrand factor (VWF), a multimeric plasma glycoprotein that plays a key role in platelet adhesion to the subendothelium and acts as a carrier of factor VIII (FVIII) in blood. Patients with VWD experience bleeding symptoms that are mainly localized in mucous membranes and soft tissues, and their severity depends on the degree of the primary reduction in VWF and the secondary deficiency of FVIII in plasma. Because VWD patients are also at increased risk of perioperative bleeding, a prophylactic treatment aimed to correct the dual haemostatic defect (i.e. VWF and FVIII) is warranted. This review summarizes knowledge on the current management of patients undergoing major surgery, focusing on the peri-surgical laboratory monitoring of replacement therapy with VWF/FVIII concentrates. We suggest to monitor plasma levels of FVIII coagulant activity in the postoperative period rather than a surrogate maker of platelet-binding VWF activity as the ristocetin cofactor assay and its recent modifications.

Tailoring hemostatic therapies to lower inhibitor development in previously untreated patients with severe hemophilia A.

After technological progress provided safer therapeutic products for patients with hemophilia A, the development of alloantibodies (inhibitors) neutralizing the coagulant activity of infused factor VIII (FVIII) remains the most serious complication of replacement therapy, predisposing patients to greater morbidity and causing higher treatment costs. The pathogenesis of inhibitors, which develop at a high rate in previously untreated children with severe hemophilia A, is multifactorial, resulting from complex interactions between genetic and environmental factors. Among non-genetic determinants, a key role is played by treatment-related factors, including the source of FVIII product (i.e., plasma derived or recombinant) and the mode of replacement therapy delivery (i.e., intensity, prophylaxis vs. on demand). We review the potential interventions on these modifiable factors that may help to lower the rate of inhibitor development. In addition, interest is currently directed toward the potential for lesser immunogenicity of novel hemostatic agents designed to decrease the dosing frequency or avoid/delay the need of FVIII replacement therapy.

Straightforward synthesis of a novel ring-fused pyrazole-lactam and in vitro cytotoxic activity on cancer cell lines.

In this paper a straightforward synthesis of a novel pyrazole derivative is reported. Prominent feature of this synthetic process is a 1,3-Dipolar Cycloaddition of a suitable nitrile imine with an activated α,ß-unsaturated lactam to afford directly and regioselectively the corresponding ring-fused pyrazole. Having obtained the central core of the synthetic target, a double stepwise functionalization with a "side chain" characterized by a terminal cyclic aliphatic amine was carried out. This molecular structure was designed to interact strongly with typical biological residues, and indeed it showed potent anticancer capability: in vitro cytotoxicity test on five different cancer cell lines showed interesting IC50 values in the range of 15-60 µM for exposure time of 24-72 h, thus resulting comparable with commercially available and nowadays therapeutically exploited anticancer compounds, such as 5-FU and NVP-BEZ235.

Gait analysis in children with haemophilia: first Italian experience at the Turin Haemophilia Centre.

AIM: To investigate the functional status in haemophilia patients referred to an Italian paediatric haemophilia centre using gait analysis, verifying any differences between mild, moderate or severe haemophilia at a functional level. METHODS: Forty-two patients (age 4-18) presenting to the Turin Paediatric Haemophilia Centre who could walk independently were included. Therapy included prophylaxis (n = 21), on-demand (n = 17) or immune tolerance induction + inhibitor (n = 4). Patients performed a test of gait analysis. Temporal, spatial and kinematic parameters were calculated for patient subgroups by disease severity and background treatment, and compared with normal values. RESULTS: Moderate (35.7%) or severe (64.3%) haemophilia patients showed obvious variations from normal across a variety of temporal and spatial gait analysis parameters, including step speed and length, double support, swing phase, load asymmetry, stance phase, swing phase and speed. Kinematic parameters were characterized by frequent foot external rotation with deficient plantar flexion during the stance phase, retropelvic tilt, impaired power generation distally and reduced ground reaction forces. Both Gait Deviation Index and Gait Profile Score values for severe haemophilia patients indicated abnormal gait parameters, which were worst in patients with a history of past or current use of inhibitors and those receiving on-demand therapy. CONCLUSION: Functional evaluation identified changes in gait pattern in patients with severe and moderate haemophilia, compared with normal values. Gait analysis may be a useful tool to facilitate early diagnosis of joint damage, prevent haemophilic arthropathy, design a personalized rehabilitative treatment and monitor functional status over time.