Analysis of phytocannabinoids in hemp seeds, sprouts and microgreens.

Hemp-sprouts are emerging as a new class of attractive functional food due to their numerous health benefits when compared to other sprout species. Indeed, the high content of beneficial components including polyphenols and flavonoids makes this type of food a promising and successful market. However, the available literature on this topic is limited and often conflicting as regards to the content of phytocannabinoids. High-performance liquid chromatography coupled to high-resolution mass spectrometry (HPLC-HRMS) was applied in an untargeted metabolomics fashion to extracts of hemp seeds, sprouts and microgreens of nine different genotypes. Both unsupervised and supervised multivariate statistical analysis was performed to reveal variety-specific profiles of phytocannabinoids with surprisingly remarkable levels of phytocannabinoids even in chemotype V samples. Furthermore, a targeted HPLC-HRMS analysis was carried out for the quantitative determination of the major phytocannabinoids including CBDA, CBD, CBGA, CBG, CBCA, CBC, THCA, and trans-Δ9-THC. The last part of the study was focused on the evaluation of the enantiomeric composition of CBCA in hemp seeds, sprouts and microgreens in the different varieties by HPLC-CD (HPLC with online circular dichroism). Chiral analysis of CBCA showed a wide variability of its enantiomeric composition in the different varieties, thus contributing to the understanding of the intriguing stereochemical behavior of this compound in an early growth stage. However, further investigation is needed to determine the genetic factors responsible for the low enantiopurity of this compound.

Clinical and radiological risk factors for poor outcomes in patients with spontaneous muscle hematomas.

PURPOSE: Spontaneous muscle hematomas (SMH) are frequently seen in the Emergency Department (ED), particularly as a complication of anticoagulation treatments. To date, there are no standard guidelines for the management of this condition in the ED. This work aims to identify clinical-radiological parameters of SMH at risk of poor outcomes. METHOD: This is a retrospective, observational cohort study conducted in an urban teaching hospital from 2016 to 2019. A multivariate logistic regression analysis was performed to identify parameters independently associated with an adverse outcome defined as the need for treatment (blood products, TAE, surgery) or hospitalization. The parameters analyzed were hematoma size, anticoagulation therapy, age, and the Charlson Comorbidity Index (CCI). ROC analysis was performed to identify the best cut-off hematoma size value to predict poor outcomes. RESULTS: Our study enrolled 231 patients aged between 18 and 96 years, with a mean age of 67 years. In our population, 125 patients (54.1 % %) were on anticoagulant therapy. Multivariate analysis showed that an SMH diameter > 5.5 cm was independently associated with poor outcome ((odds Ratio [95 % CI] 4,009 [1,786-9,001], p 0.001). Among clinical parameters, only advanced age was proved to be an independent predictor of adverse outcomes (odds Ratio [95 % CI] 1,035 [1,003-1,069], p = 0.033) CONCLUSIONS: Our data suggest that an SMH diameter greater than 5.5 cm on a CT scan and advanced age are predictors of poor outcomes. Surprisingly, anticoagulant therapy seems to play a minor role in the outcome of SMHs.

Predictors of Efficacy of Janus Kinase Inhibitors in Patients Affected by Ulcerative Colitis.

Personalised medicine and the identification of predictors of the efficacy of specific drugs represent the ultimate goal for the treatment of ulcerative colitis (UC) in order to break the current therapeutic ceiling. JAK inhibitors are a new class of advanced therapies, orally administered, showing a good profile of efficacy and safety in both randomised controlled trials (RCTs) and real-world studies. Unfortunately, to date, it is not possible to draw the ideal profile of a patient maximally benefiting from this class of drugs to guide clinicians' therapeutic choices. Baseline clinical activities and inflammatory biomarkers, as well as their early variation after treatment initiation, emerged as the main predictors of efficacy from post hoc analyses of RCTs with tofacitinib. Similar findings were also observed in the real-life studies including mainly patients with a history of pluri-refractoriness to biological therapies. At last, a few new biomarkers have been explored, even though they have not been validated in large cohorts. This paper provides a review of the current knowledge on clinical variables and biomarkers predicting response to JAK inhibitors in UC.

Optimizing the "Time to pregnancy" in women with multiple sclerosis: the OPTIMUS Delphi survey.

Background: The debate on how to manage women affected by multiple sclerosis (MS) during reproductive age is still open, as is the issue of fertility in such patients. Main issue regard the identification of the optimal window for pregnancy and how to deal with medical therapy before and during conception. The aim of this Delphi consensus was to collect the opinions of a multidisciplinary group, involving reproductive medicine specialists and neurologists with experience in the management of multiple sclerosis women with reproductive desire. Methods: Four experts plus scientific coordinators developed a questionnaire distributed online to 10 neurologists and later discussed the responses and amended a list of statements. The statements were then distributed via an online survey to 23 neurologists (comprising the first 10), who voted on their level of agreement/disagreement with each statement. Consensus was achieved if agreement or disagreement with a statement exceeded 66%. Results: Twenty-one statements reached consensus after two rounds of voting, leading to the following main recommendations: (1) Fertility evaluation should be suggested to wMS, in case of the need to shorten time to pregnancy and before treatment switch in women on DMTs contraindicated in pregnancy, particularly in case of highly active disease and age > 35 years. (2) ART should not be discouraged in wMS, but the use of DMTs until pregnancy confirmation should be suggested; ART may be considered in order to reduce time to pregnancy in MS women with a reduced ovarian reserve and/or age > 35 years, but in case of an expected poor ART prognosis and the need for more than one ART cycle, a switch to a high-efficacy DMD before ART should be offered. (3) Oocyte cryopreservation may be considered in women with reduced ovarian reserve, with unpredictable time to complete diagnostic workup and achieve disease control; a risk/cost-benefit analysis must be performed in women >35 years, considering the diminished ovarian reserve. Conclusion: This consensus will help MS neurologists to support family planning in wMS, respecting MS therapeutic needs while also taking into account the safety and impact of advancing age on fertility.

Assisted Reproductive Technology and Disease Management in Infertile Women with Multiple Sclerosis.

Multiple sclerosis (MS) predominantly affects women of fertile age. Various aspects of MS could impact on fertility, such as sexual dysfunction, endocrine alterations, autoimmune imbalances, and disease-modifying therapies (DMTs). The proportion of women with MS (wMS) requesting infertility management and assisted reproductive technology (ART) is increasing over time. In this review, we report on data regarding ART in wMS and address safety issues. We also discuss the clinical aspects to consider when planning a course of treatment for infertility, and provide updated recommendations to guide neurologists in the management of wMS undergoing ART, with the goal of reducing the risk of disease activation after this procedure. According to most studies, there is an increase in relapse rate and magnetic resonance imaging activity after ART. Therefore, to reduce the risk of relapse, ART should be considered in wMS with stable disease. In wMS, especially those with high disease activity, fertility issues should be discussed early as the choice of DMT, and fertility preservation strategies might be proposed in selected cases to ensure both disease control and a safe pregnancy. For patients with stable disease taking DMTs compatible with pregnancy, treatment should not be interrupted before ART. If the ongoing therapy is contraindicated in pregnancy, then it should be switched to a compatible therapy. Prior to beginning fertility treatments in wMS, it would be reasonable to assess vitamin D serum levels, thyroid function and its antibody serum levels; start folic acid supplementation; and ensure smoking and alcohol cessation, adequate sleep, and food hygiene. Cervico-vaginal swabs for Ureaplasma urealyticum, Mycoplasma hominis, and Chlamydia trachomatis, as well as serology for viral hepatitis, HIV, syphilis, and cytomegalovirus, should be performed. Steroids could be administered under specific indications. Although the available data do not clearly show a definite raised relapse risk associated with a specific ART protocol, it seems reasonably safe to prefer the use of gonadotropin-releasing hormone (GnRH) antagonists for ovarian stimulation. Close clinical and radiological monitoring is reasonably recommended, particularly after hormonal stimulation and in case of pregnancy failure.

Ectrodactyly-ectodermal dysplasia-clefting syndrome. Prenatal prospective ultrasound diagnosis.

OBJECTIVE: Prenatal diagnosis of the Ectrodactyly-Ectodermal dysplasia-clefting (EEC) syndrome has been based upon the detection of ectrodactyly, in association with facial clefting and/or positive family history. Our aim is to describe other ultrasonographic features indicating the presuntive diagnosis, regardless of genetic diagnosis, especially in cases of negative family history. MATERIALS AND METHODS: A case report and a review of the literature was assessed. RESULTS: Our case report showed a singleton foetus "lobster claw" deformities of hands and feet. Paternal history revealed bilateral agenesia of two fingers. Through literature, 15 case reports of prenatal diagnosis of EEC syndrome were found, 14 of which were eligible for our systematic review. The 33% of cases (5/15) had a familiar history of EEC, thus, we found one case of consanguinity of parents. Anomalies EEC-related were recognized in the 40% of cases (6/15). An association with genitourinary anomalies was found in 30% (5/15) of them. CONCLUSIONS: A strong suspicion of final diagnosis of EEC may be done in the presence of ectrodactyly, facial clefting and urinary malformation especially in cases of negative family history. More attention should be given to a genetic counseling, especially to understand a possible relation to other genetic syndromes.

Synthesis and pharmacological activity of the epimers of hexahydrocannabinol (HHC).

Cannabis is a multifaceted plant with numerous therapeutic properties on one hand, and controversial psychotropic activities on the other hand, which are modulated by CB1 endocannabinoid receptors. Δ9-Tetrahydrocannabinol (Δ9-THC) has been identified as the main component responsible for the psychotropic effects, while its constitutional isomer cannabidiol (CBD) has shown completely different pharmacological properties. Due to its reported beneficial effects, Cannabis has gained global popularity and is openly sold in shops and online. To circumvent legal restrictions, semi-synthetic derivatives of CBD are now frequently added to cannabis products, producing "high" effects similar to those induced by Δ9-THC. The first semi-synthetic cannabinoid to appear in the EU was obtained through cyclization and hydrogenation of CBD, and is known as hexahydrocannabinol (HHC). Currently, there is limited knowledge regarding HHC, its pharmacological properties, and its prevalence, as it is not commonly investigated in routine toxicological assays. In this study, synthetic strategies were explored to obtain an excess of the active epimer of HHC. Furthermore, the two epimers were purified and individually tested for their cannabinomimetic activity. Lastly, a simple and rapid chromatographic method employing a UV detector and a high-resolution mass spectrometer was applied to identify and quantify up to ten major phytocannabinoids, as well as the HHC epimers, in commercial cannabis samples.

Predicting ICU admission and death in the Emergency Department: A comparison of six early warning scores.

AIM: To compare the ability of the most used Early Warning Scores (EWS) to identify adult patients at risk of poor outcomes in the emergency department (ED). METHODS: Single-center, retrospective observational study. We evaluated the digital records of consecutive ED admissions in patients ≥ 18 years from 2010 to 2019 and calculated NEWS, NEWS2, MEWS, RAPS, REMS, and SEWS based on parameters measured on ED arrival. We assessed the discrimination and calibration performance of each EWS in predicting death/ICU admission within 24 hours using ROC analysis and visual calibration. We also measured the relative weight of clinical and physiological derangements that identified patients missed by EWS risk stratification using neural network analysis. RESULTS: Among 225,369 patients assessed in the ED during the study period, 1941 (0.9%) were admitted to ICU or died within 24 hours. NEWS was the most accurate predictor (area under the receiver operating characteristic [AUROC] curve 0.904 [95% CI 0.805-0.913]), followed by NEWS2 (AUROC 0.901). NEWS was also well calibrated. In patients judged at low risk (NEWS < 2), 359 events occurred (18.5% of the total). Neural network analysis revealed that age, systolic BP, and temperature had the highest relative weight for these NEWS-unpredicted events. CONCLUSIONS: NEWS is the most accurate EWS for predicting the risk of death/ICU admission within 24 h from ED arrival. The score also had a fair calibration with few events occurring in patients classified at low risk. Neural network analysis suggests the need for further improvements by focusing on the prompt diagnosis of sepsis and the development of practical tools for the measurement of the respiratory rate.

Ovarian reserve in patients with multiple sclerosis: A systematic review and meta-analysis.

OBJECTIVE: To summarize recent evidence about ovarian reserve markers in women affected by multiple sclerosis (MS) compared with healthy controls, as women with MS seem to be characterized by lower anti-Müllerian hormone (AMH) levels. METHODS: The research was conducted using PubMed (MEDLINE), Scopus, ClinicalTrial.gov, OVID and Cochrane Library from inception of each database to June 30, 2022. Studies comparing ovarian reserve markers between women with MS and healthy controls were considered eligible for inclusion. The primary outcome was serum AMH (ng/mL) levels. Results were reported as pooled odds ratio (OR) for categorical outcomes and as mean difference (MD) for continuous variables, with their 95% confidence intervals (CIs). The random effect model of DerSimonian and Laird was adopted for all analyses. A P-value less than 0.05 was considered significant. RESULTS: Serum AMH circulating levels were not significantly different (MD -0.25, 95% CI -0.83 to 0.32; P = 0.390), as well as blood levels of follicle-stimulating hormone or ovarian volume. However, antral follicle count (AFC) and estradiol blood levels were significantly lower, and luteinizing hormone (LH) levels were significantly higher in women with MS than in controls. CONCLUSION: A significant difference in AFC, estradiol and LH levels was observed, but not for AMH levels.

The impact of COVID-19 pandemic on obstetrics and gynecology hospitalization rate and on reasons for seeking emergency care: a systematic review and meta-analysis.

BACKGROUND: During the lockdown due to COVID-19 pandemic, utilization of emergency care units has been reported to be reduced for obstetrical and gynaecological reasons. The aim of this systematic review is to assess if this phenomenon reduced the rate of hospitalizations for any reason and to evaluate the main reasons for seeking care in this subset of the population. METHODS: The search was conducted using the main electronic databases from January 2020 to May 2021. The studies were identified with the use of a combination of: "emergency department" OR "A&E" OR "emergency service" OR "emergency unit" OR "maternity service" AND "COVID-19" OR "COVID-19 pandemic" OR "SARS-COV-2" and "admission" OR "hospitalization". All the studies that evaluated women going to obstetrics & gynecology emergency department (ED) during the COVID-19 pandemic for any reason were included. RESULTS: The pooled proportion (PP) of hospitalizations increased from 22.7 to 30.6% during the lockdown periods, in particular from 48.0 to 53.9% for delivery. The PP of pregnant women suffering from hypertensive disorders increased (2.6 vs 1.2%), as well as women having contractions (52 vs 43%) and rupture of membranes (12.0 vs 9.1%). Oppositely, the PP of women having pelvic pain (12.4 vs 14.4%), suspected ectopic pregnancy (1.8 vs 2.0), reduced fetal movements (3.0 vs 3.3%), vaginal bleeding both for obstetrical (11.7 vs 12.8%) and gynecological issues (7.4 vs 9.2%) slightly reduced. CONCLUSION: During the lockdown, an increase in the proportion of hospitalizations for obstetrical and gynecological reasons has been registered, especially for labor symptoms and hypertensive disorders.

Enantioseparation of chiral phytocannabinoids in medicinal cannabis.

The evaluation of the chiral composition of phytocannabinoids in the cannabis plant is particularly important as the pharmacological effects of the (+) and (-) enantiomers of these compounds are completely different. Chromatographic attempts to assess the presence of the minor (+) enantiomers of the main phytocannabinoids, cannabidiolic acid (CBDA) and trans-Δ9-tetrahydrocannabinolic acid (trans-Δ9-THCA), were carried out on heated plant extracts for the determination of the corresponding decarboxylated species, cannabidiol (CBD) and trans-Δ9-tetrahydrocannabinol (trans-Δ9-THC), respectively. This process produces an altered phytocannabinoid composition with several new and unknown decomposition products. The present work reports for the first time the stereoselective synthesis of the pure (+) enantiomers of the main phytocannabinoids, trans-CBDA, trans-Δ9-THCA, trans-CBD and trans-Δ9-THC, and the development and optimization of an achiral-chiral liquid chromatography method coupled to UV and high-resolution mass spectrometry detection in reversed phase conditions (RP-HPLC-UV-HRMS) for the isolation of the single compounds and evaluation of their actual enantiomeric composition in plant. The isolation of the peaks with the achiral stationary phase ensured the absence of interferences that could potentially co-elute with the analytes of interest in the chiral analysis. The method applied to the Italian medicinal cannabis variety FM2 revealed no trace of the (+) enantiomers for all phytocannabinoids under investigation before and after decarboxylation, thus suggesting that the extraction procedure does not lead to an inversion of configuration.

Green Synthesis of Iridium Nanoparticles from Winery Waste and Their Catalytic Effectiveness in Water Decontamination.

An environmentally friendly procedure was adopted for the first time to prepare green iridium nanoparticles starting from grape marc extracts. Grape marcs, waste of Negramaro winery production, were subjected to aqueous thermal extraction at different temperatures (45, 65, 80, and 100 °C) and characterized in terms of total phenolic contents, reducing sugars, and antioxidant activity. The results obtained showed an important effect of temperature with higher amounts of polyphenols and reducing sugars and antioxidant activity in the extracts with the increase of temperature. All four extracts were used as starting materials to synthesize different iridium nanoparticles (Ir-NP1, Ir-NP2, Ir-NP3, and Ir-NP4) that were characterized by Uv-Vis spectroscopy, transmission electron microscopy, and dynamic light scattering. TEM analysis revealed the presence of very small particles in all samples with sizes in the range of 3.0-4.5 nm with the presence of a second fraction of larger nanoparticles (7.5-17.0 nm) for Ir-NPs prepared with extracts obtained at higher temperatures (Ir-NP3 and Ir-NP4). Since the wastewater remediation of toxic organic contaminants on catalytic reduction has gained much attention, the application of the prepared Ir-NPs as catalysts towards the reduction of methylene blue (MB), chosen as the organic dye model, was evaluated. The efficient catalytic activity of Ir-NPs in the reduction of MB by NaBH4 was demonstrated and Ir-NP2 was prepared using the extract obtained at 65 °C, showing the best catalytic performance, with a rate constant of 0.527 ± 0.012 min-1 and MB reduction of 96.1% in just six min, with stability for over 10 months.

Malignant Solitary Fibrous Tumours of the Pleura Are Not All the Same: Analysis of Long-Term Outcomes and Evaluation of Risk Stratification Models in a Large Single-Centre Series.

Introduction: Malignant solitary fibrous tumours of the pleura (mSFTP) are extremely rare diseases (<5% of all pleural neoplasms) with unpredictable behaviour. Surgery remains the standard of care for these tumours; however, estimating patient prognosis and planning follow-up remain challenging. Several risk stratification models have been proposed, but a classification with diagnostic and prognostic potential has not been well standardised yet. The aim of this study was to analyse the clinicopathological data of mSFTP to investigate their prognostic features and to compare the performance of three risk stratification models proposed in the literature. Methods: Observational retrospective cohort study on all proven cases of mSFTP surgically resected with radical intent between 2000 and 2019 in a single centre. Demographic, surgical and pathological data were examined. All patients were risk-stratified by using three prediction models: modified Demicco, De Perrot and Tapias. Overall survival (OS) and disease-free survival (DFS) were analysed. Results: There were 21 men and 13 women (median age, 67 years, range, 23-83 years). Twenty-one patients (62%) were symptomatic. The median follow-up was 111 months (range, 6-258 months). The 5-year OS and DFS were 81.2% and 77.4%, respectively. Nine patients (26.5%) experimented recurrences. At univariate analysis, the presence of necrosis (p = 0.019), nuclear atypia (p = 0.006), dimension greater than 11.5 cm (median value of our cohort) (p = 0.037) and relapse/disease progression (p = 0.001) were independent prognostic factor of worse OS. The administration of adjuvant treatment was a protective independent factor for survival (p = 0.001). Radicality of resection (p = 0.005); tumour dimension (p = 0.013), presence of necrosis (p = 0.041) and nuclear atypia (p = 0.007) and pleural pattern (p = 0.011) were independent prognostic factors of worse DFS. Analysing the three risk stratification models, the Tapias score was revealed as the best index to predict both OS (p = 0.002) and DFS (p = 0.047) in patients with mSFTP. Conclusions: Using the risk stratification model proposed by Tapias, patients with the highest risk of recurrence could be identified at the time of surgery to establish a more frequent imaging surveillance and longer follow-up. The role of adjuvant treatment in mSFTP therapy has not been established yet, but further analysis on patients with a high risk of recurrence, stratified according to risk models, along with biomolecular panels may tailor future post-surgical therapies.

Do Anti-SARS-CoV-2 Monoclonal Antibodies Have an Impact on Pregnancy Outcome? A Systematic Review and Meta-Analysis.

Monoclonal antibodies (mAbs) have been used as a rescue strategy for pregnant women affected by COVID-19. To explore its impact on maternal-fetal health, we included all observational studies reporting maternal, fetal, delivery and neonatal outcomes in women who underwent mAbs infusion for COVID-19. Primary outcome was the percentage of preterm delivery. We used meta-analyses of proportions to combine data for maternal, fetal, delivery and neonatal outcome of women treated with mAbs for COVID-19 and reported pooled proportions and their 95% confidence intervals (CIs) for categorical variables or mean difference (MD) with their 95% confidence intervals for continuous variables. Preterm birth was observed in 22.8% of cases (95% CI 12.9-34.3). Fetal distress was reported in 4.2% (95% CI 1.6-8.2). Gestational hypertension and pre-eclampsia were observed in 3.0% (95% CI 0.8-6.8) and 3.4% (95% CI 0.8-7.5) of cases, respectively. Fetal growth restriction was observed in 3.2% of fetuses (95% CI 0.8-7.0). Secondary prophylaxis with mAbs is currently considered the best treatment option for people with mild to moderate COVID-19 disease. More attention should be paid to infants born from mothers who were treated with mAbs, for the risk of immunosuppression.

The role of ultrasound in the diagnosis and management of postpartum hemorrhage.

Postpartum hemorrhage (PPH) is the leading cause of death or severe morbidity for the mother after delivery. As a consequence healthcare staff working in the delivery room should be trained to perform a prompt diagnosis and adequate management of PPH. Uneventful outcome is induced correct identification of the underlying cause of hemorrhage. Ultrasound is a promising technique for the prompt diagnosis of PPH etiology. Indeed, it is easily available, with relatively low cost, not using ionizing radiation, and can be used in different settings including the labor room, the operating theater and at the bedside of an affected women. In order to be effective Obstetricians should have an adequate knowledge of postpartum ultrasonography. In this article, we will review the sonographic findings occurring in PPH, in the differential diagnosis of the underlying cause of hemorrhage, that include retained placenta, morbidly adherent placenta, rupture of the uterus uterine, vascular anomalies of the uterine arteries and uterine inversion. We will also provide an algorithm to manage PPH according to the ultrasonographic findings.

Clinical, laboratory and ultrasonographic risk factors for uterine artery arteriosclerosis: Insights for uterus transplantation.

OBJECTIVE: To assess uterine artery arteriosclerosis prevalence in women undergoing total hysterectomy for benign diseases, and any associations between clinical, laboratory, and ultrasound factors and uterine artery arteriosclerosis occurrence. METHODS: A single center, observational, prospective, cohort study was performed enrolling all symptomatic patients scheduled for total hysterectomy from May to December 2021. Our outcomes were: uterine artery arteriosclerosis prevalence and the difference in clinical, laboratory, and ultrasonographic factors between patients with and without uterine artery arteriosclerosis. RESULTS: Forty women were included. Uterine artery arteriosclerosis prevalence was 70%. Body mass index (BMI) (P = 0.04) and triglycerides (P = 0.04) were significantly higher in patients with uterine artery arteriosclerosis than in patients without; while high-density lipoprotein (HDL) (P = 0.02) was significantly lower. Uterine arteries with arteriosclerosis showed higher peak systolic velocity (PSV) values compared with vessels without arteriosclerosis (P = 0.05). CONCLUSIONS: Uterine artery arteriosclerosis shows a high prevalence in women undergoing total hysterectomy for benign diseases. Higher BMI, serum triglycerides, and PSV, and lower serum HDL appear as risk factors for uterine artery arteriosclerosis.

Use of artificial intelligence in obstetrics: not quite ready for prime time.

Artificial intelligence is finding several applications in healthcare settings. This study aimed to report evidence on the effectiveness of artificial intelligence application in obstetrics. Through a narrative review of literature, we described artificial intelligence use in different obstetrical areas as follows: prenatal diagnosis, fetal heart monitoring, prediction and management of pregnancy-related complications (preeclampsia, preterm birth, gestational diabetes mellitus, and placenta accreta spectrum), and labor. Artificial intelligence seems to be a promising tool to help clinicians in daily clinical activity. The main advantages that emerged from this review are related to the reduction of inter- and intraoperator variability, time reduction of procedures, and improvement of overall diagnostic performance. However, nowadays, the diffusion of these systems in routine clinical practice raises several issues. Reported evidence is still very limited, and further studies are needed to confirm the clinical applicability of artificial intelligence. Moreover, better training of clinicians designed to use these systems should be ensured, and evidence-based guidelines regarding this topic should be produced to enhance the strengths of artificial systems and minimize their limits.

Toward Plasmonic Neural Probes: SERS Detection of Neurotransmitters through Gold-Nanoislands-Decorated Tapered Optical Fibers with Sub-10 nm Gaps.

Integration of plasmonic nanostructures with fiber-optics-based neural probes enables label-free detection of molecular fingerprints via surface-enhanced Raman spectroscopy (SERS), and it represents a fascinating technological horizon to investigate brain function. However, developing neuroplasmonic probes that can interface with deep brain regions with minimal invasiveness while providing the sensitivity to detect biomolecular signatures in a physiological environment is challenging, in particular because the same waveguide must be employed for both delivering excitation light and collecting the resulting scattered photons. Here, a SERS-active neural probe based on a tapered optical fiber (TF) decorated with gold nanoislands (NIs) that can detect neurotransmitters down to the micromolar range is presented. To do this, a novel, nonplanar repeated dewetting technique to fabricate gold NIs with sub-10 nm gaps, uniformly distributed on the wide (square millimeter scale in surface area), highly curved surface of TF is developed. It is experimentally and numerically shown that the amplified broadband near-field enhancement of the high-density NIs layer allows for achieving a limit of detection in aqueous solution of 10-7  m for rhodamine 6G and 10-5  m for serotonin and dopamine through SERS at near-infrared wavelengths. The NIs-TF technology is envisioned as a first step toward the unexplored frontier of in vivo label-free plasmonic neural interfaces.

Cryopreservation of ovarian tissue: the biggest challenge of oncofertility.

Survival rates after cancer diagnosis and treatment have been raising through the last decades. Nowadays, oncofertility represents a useful strategy for young women affected by cancer to preserve their ovarian function and their family planning opportunity. Apart from more diffused techniques as cryopreservation of mature oocytes after controlled ovarian stimulation and gonadal downregulation with gonadotropin-releasing hormone agonist depots, the cryopreservation of the cortical region of the ovarian tissue, which contains 90% of the follicular reserve, and later autologous transplant represent a possible and intriguing strategy. Nonetheless, the safety of the procedure is still a matter of debate and is a topic of great interest in both oncologic and reproductive fields. Especially, in order to improve the efficacy of the strategy the open questions are: 1) how to search for malignant cells; 2) slow freezing vs. vitrification; 3) state of the art on the "artificial ovary." The aim of this review was to summarize the recent advances in ovarian tissue cryopreservation and present future perspectives.

Post-intubation tracheal lacerations: Risk-stratification and treatment protocol according to morphological classification.

Background: Post-intubation tracheal laceration (PITL) is a rare condition (0.005% of intubations). The treatment of choice has traditionally been surgical repair. Following our first report in 2010 of treatment protocol tailored to a risk-stratified morphological classification there is now clear evidence that conservative therapy represents the gold standard in the majority of patients. In this paper we aim to validate our risk-stratified treatment protocol through the largest ever reported series of patients. Methods: This retrospective analysis is based on a prospectively collected series (2003-2020) of 62 patients with PITL, staged and treated according to our revised morphological classification. Results: Fifty-five patients with Level I (#8), II (#36) and IIIA (#11) PITL were successfully treated conservatively. Six patients with Level IIIB injury and 1 patient with Level IV underwent a surgical repair of the trachea. No mortality was reported. Bronchoscopy confirmed complete healing in all patients by day 30. Statistical analysis showed age only to be a risk factor for PITL severity. Conclusions: Our previously proposed risk-stratified morphological classification has been validated as the major tool for defining the type of treatment in PITL.