miR-125 in Breast Cancer Etiopathogenesis: An Emerging Role as a Biomarker in Differential Diagnosis, Regenerative Medicine, and the Challenges of Personalized Medicine.

Breast Cancer (BC) is one of the most common cancer types worldwide, and it is characterized by a complex etiopathogenesis, resulting in an equally complex classification of subtypes. MicroRNA (miRNA or miR) are small non-coding RNA molecules that have an essential role in gene expression and are significantly linked to tumor development and angiogenesis in different types of cancer. Recently, complex interactions among coding and non-coding RNA have been elucidated, further shedding light on the complexity of the roles these molecules fulfill in cancer formation. In this context, knowledge about the role of miR in BC has significantly improved, highlighting the deregulation of these molecules as additional factors influencing BC occurrence, development and classification. A considerable number of papers has been published over the past few years regarding the role of miR-125 in human pathology in general and in several types of cancer formation in particular. Interestingly, miR-125 family members have been recently linked to BC formation as well, and complex interactions (competing endogenous RNA networks, or ceRNET) between this molecule and target mRNA have been described. In this review, we summarize the state-of-the-art about research on this topic.

Comparison of ECG Saline-Conduction Technique and ECG Wire-Based Technique for Peripherally Inserted Central Catheter Insertion: A Randomized Controlled Trial.

(1) Background: The peripherally inserted central catheter (PICC) is commonly used in medicine. The tip position was shown to be a major determinant in PICC function and related complications. Recent advances in ECG guidance might facilitate daily practice. This study aimed to compare two ECG techniques, in terms of their tip-position accuracy, puncture site layout, and signal quality; (2) Methods: This randomized open study (1:1) included 320 participants. One PICC guidance technique used ECG signal transmission with saline (ST); the other technique used a guidewire (WT). Techniques were compared by the distance between the catheter tip and the cavoatrial junction (DCAJ) on chest X-rays, insertion-point hemostasis time, and the extracorporeal catheter length between the hub and the insertion point; (3) Results: The mean DCAJs were significantly different between ST (1.36 cm, 95% CI: 1.22-1.37) and WT (1.12 cm, 95% CI: 0.98-1.25; p = 0.013) groups. When DCAJs were classified as optimal, suboptimal, or inadequate, the difference between techniques had limited clinical impact (p = 0.085). However, the hemostasis time at the puncture site was significantly better with WT (no delay in 82% of patients) compared to ST (no delay in 50% of patients; p < 0.001). Conversely, ST achieved optimal and suboptimal extracorporeal lengths significantly more frequently than WT (100% vs. 66%; p < 0.001); (4) Conclusions: ECG guidance technologies achieved significantly different tip placements, but the difference had minimal clinical impact. Nevertheless, each technique displayed an important drawback at the PICC insertion point: the extracorporeal catheter was significantly longer with WT and the hemostasis delay was significantly longer with ST.

Wernicke Syndrome: Case Report and Literature Review of Contributing Factors-Can Malpractice Dynamics Be Identified?

Wernicke Encephalopathy (WE) is a neurological acute syndrome related to vitamin B1 deficiency and is relatively common in patients with chronic alcoholism. In the case of Hyperemesis Gravidarum, thiamine body stores become unable to meet the increased demand, resulting in acute deficiency. WE is associated with typical clinical and radiological findings. Treatment pathways rely on thiamine replacement. The case herein reported is centered around a 33-year-old diabetic patient at 12 weeks of gestation, with WE due to hyperemesis gravidarum. The disease manifested itself with weakness, mental confusion, headache, and impaired vision. The diagnosis was established after the detection of typical findings by MRI. Thirty days after therapy was started, most of the patient's neurological disorders were resolved. The patient was discharged 40 days later with instructions to continue daily thiamine supplementation. The pregnancy outcome was good. Unfortunately, mild ataxia persisted in 2-year follow-up as a long-term consequence. When diagnosed and treated, WE has a favorable prognosis. However, roughly 80% of patients experience memory loss, which may continue for a long time, while gait disorders reportedly affect about 35% of patients. Mild ataxia and dysmetria may persist, too. We reviewed the scientific literature on WE in women with HG until February 2023. Hardly any authors report data on long-term sequelae. Our report emphasizes how important it is to take into consideration this complication in clinical practice, referring to published guidelines and recommendations. Neurological maternal sequelae can demonstrably persist despite early diagnosis and appropriate management. For this reason, a long-term follow-up is recommended. Wernicke syndrome management cannot yet rely on well-established conclusive guidelines; hence, a cautionary approach ought to be prioritized in order to ensure medicolegal soundness.

Measuring the composition of the tumor microenvironment with transcriptome analysis: past, present and future.

Interactions between tumor cells and immune cells in the tumor microenvironment (TME) play a vital role the mechanisms of immune evasion, by which cancer cells escape immune elimination. Thus, the characterization and quantification of different components in the TME is a hot topic in molecular biology and drug discovery. Since the development of transcriptome sequencing in bulk tissue, single cells and spatial dimensions, there are increasing methods emerging to deconvolute and subtype the TME. This review discusses and compares such computational strategies and downstream subtyping analyses. Integrative analyses of the transcriptome with other data, such as epigenetics and T-cell receptor sequencing, are needed to obtain comprehensive knowledge of the dynamic TME.

Stem Cells and Infertility: A Review of Clinical Applications and Legal Frameworks.

Infertility is a condition defined by the failure to establish a clinical pregnancy after 12 months of regular, unprotected sexual intercourse or due to an impairment of a person's capacity to reproduce either as an individual or with their partner. The authors have set out to succinctly investigate, explore, and assess infertility treatments, harnessing the potential of stem cells to effectively and safely treat infertility; in addition, this paper will present the legal and regulatory complexities at the heart of stem cell research, with an overview of the legislative state of affairs in six major European countries. For couples who cannot benefit from assisted reproductive technologies (ART) to treat their infertility, stem-cells-based approaches have been shown to be a highly promising approach. Nonetheless, lingering ethical and immunological uncertainties require more conclusive findings and data before such treatment avenues can become mainstream and be applied on a large scale. The isolation of human embryonic stem cells (ESCs) is ethically controversial, since their collection involves the destruction of human embryonic tissue. Overall, stem cell research has resulted in important new breakthroughs in the treatment of infertility. The effort to untangle the complex web of ethical and legal issues associated with such therapeutic approaches will have to rely on evidence-based, broadly shared standards, guidelines, and best practices to make sure that the procreative rights of patients can be effectively reconciled with the core values at the heart of medical ethics.

Advancing Tailored Treatments: A Predictive Nomogram, Based on Ultrasound and Laboratory Data, for Assessing Nodal Involvement in Endometrial Cancer Patients.

Assessing lymph node metastasis is crucial in determining the optimal therapeutic approach for endometrial cancer (EC). Considering the impact of lymphadenectomy, there is an urgent need for a cost-effective and easily applicable method to evaluate the risk of lymph node metastasis in cases of sentinel lymph node (SLN) biopsy failure. This retrospective monocentric study enrolled EC patients, who underwent surgical staging with nodal assessment. Data concerning demographic, clinicopathological, ultrasound, and surgical characteristics were collected from medical records. Ultrasound examinations were conducted in accordance with the IETA statement. We identified 425 patients, and, after applying exclusion criteria, the analysis included 313 women. Parameters incorporated into the nomogram were selected via univariate and multivariable analyses, including platelet count, myometrial infiltration, minimal tumor-free margin, and CA 125. The nomogram exhibited good accuracy in predicting lymph node involvement, with an AUC of 0.88. Using a cutoff of 10% likelihood of nodal involvement, the nomogram displayed a low false-negative rate of 0.04 (95% CI 0.00-0.19) in the training set. The adaptability of this straightforward model renders it suitable for implementation across diverse clinical settings, aiding gynecological oncologists in preoperative patient evaluations and facilitating the design of personalized treatments. However, external validation is mandatory for confirming diagnostic accuracy.

Obstetric and Gynecological Admissions and Hospitalizations in an Italian Tertiary-Care Hospital during COVID-19 Pandemic: A Retrospective Analysis According to Restrictive Measures.

BACKGROUND: The national lockdown and the different restrictions applied in 2020 during the COVID-19 pandemic brought several changes to hospitalization procedures. The aim of this study was to evaluate the patterns in access to emergency services and hospitalization in a tertiary-care obstetric and gynecological emergency department (OG-ED) throughout the restrictions applied during 2020. METHODS: A single-center retrospective comparative study on data from January to December 2020 was carried out on the following timeframes: January to February 2020 (before COVID-19 pandemic), March to June 2020 (nationwide lockdown period), July to September 2020 (removal of restrictive measures), October to December 2020 (regional lockdown) and compared to the same periods of 2019. All obstetric and gynecological patients with complete medical data admitted to the OG-ED were included. RESULTS: Overall, 4233 accesses for 2019 and 3652 for 2020 were reported, with a decreasing trend of -13.7%. Between March and June 2020 (nationwide lockdown) and 2019, the overall number of patients attending the OG-ED decreased compared to July-September and October-December differences (Δ -23.5% vs. -3.1% and -5.9%; p = 0.001 respectively) for 2020-2019, but this reduction was not statistically significant when compared to January-February (Δ -23.5% vs. -18.5%; p = 0.356). No significant differences for obstetric patients (Δ -1.8% vs. -1.0% vs. -2.3% and +1.9% respectively; p = 0.883) were noted. Hospitalizations showed a stable trend with an increase between October-December 2019 and 2020 (Δ +4.6%; p = 0.001 vs. January-February (+2.4%) and March-June (+2.6%) 2019-2020), mainly related to regional lockdowns. CONCLUSIONS: In contrast to available national studies, in our institution, the overall rate of OG-ED admissions was slightly reduced with a similar trend of decrease even before COVID-19, with an increase in admissions for serious issues, despite expectations that the suspension of elective admissions and outpatient services would have led to an increase in non-urgent hospitalizations during the COVID-19 lockdown period.

Investigating the Influence of High-Speed Gantry Rotation in Cardiac CT on Motion Artifacts in Aortic Stenosis Patients Not Premedicated with ß-Blockers: The FAST-CCT Randomized Trial Protocol.

BACKGROUND: Coronary CT angiography (CCTA) is increasingly used as a non-invasive tool to assess coronary artery disease (CAD). However, CCTA is subject to motion artifacts, potentially limiting its clinical utility. Despite faster (0.35 and 0.28 s/rot) gantry rotation times, low (60-65 bpm) heartbeat is recommended, and the use of ß-blockers is often needed. Technological advancements have resulted in the development of faster rotation speeds (0.23 s/rot). However, their added value in patients not premedicated with ß-blockers remains unclear. This prospective single-center, two-arm, randomized, controlled trial aims to assess the influence of fast rotation on coronary motion artifacts, diagnostic accuracy of CCTA for CAD, and patient safety. METHODS: We will randomize a total of 142 patients aged ≥ 50 scheduled for an aortic stenosis work-up to receive CCTA with either a fast (0.23) or standard (0.28 s/rot) gantry speed. PRIMARY OUTCOME: rate of CCTAs with coronary motion artifacts hindering interpretation. SECONDARY OUTCOMES: assessable coronary segments rate, diagnostic accuracy against invasive coronary angiography (ICA), motion artifact magnitude per segment, contrast-to-noise ratio (CNR), and patient ionizing radiation dose. The local ethics committee has approved the protocol. Potential significance: FAST-CCT may improve motion artifact reduction and diagnosis quality, thus eliminating the need for rate control and ß-blocker administration. CLINICALTRIALS: gov identifier: NCT05709652.

Comparison of Maternal and Neonatal Outcomes between SARS-CoV-2 Variants: A Retrospective, Monocentric Study.

The impact of SARS-CoV-2 variants on maternal and neonatal outcomes during pregnancy is still poorly understood, and the emergence of different variants has further complicated our understanding of the virus's effects. This retrospective, monocentric study aimed to fill this knowledge gap by analyzing the outcomes of pregnant women with acute SARS-CoV-2 infection caused by the Alpha, Delta, and Omicron variants. The study, conducted between December 2020 and March 2022 at San Marco Hospital, included 313 pregnant women with confirmed SARS-CoV-2 infection. The results showed that the Delta variant was associated with a significantly higher incidence of adverse outcomes, such as premature births, maternal intensive care unit admission, intrauterine growth restriction, and small for gestational age infants. Additionally, the Delta variant was linked to lower Apgar scores, higher maternal and fetal mortality rates, and increased levels of various biomarkers indicating more severe illness. Finally, the Delta variant also presented a greater possibility of vertical transmission. These findings underscore the complexity of understanding the impact of SARS-CoV-2 on pregnancy outcomes, especially considering the distinctive characteristics of different variants. By better understanding the specific impacts of each variant, appropriate preventive measures and management strategies can be implemented to optimize maternal and neonatal outcomes.

First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial.

BACKGROUND: Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression. METHODS: EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged ≥18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540. FINDINGS: Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 26·1 months (95% CI 22·1-31·8; 149 [52%] of 284 died) versus 13·3 months (10·5-16·2; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 0·57, 95% CI 0·46-0·71; p<0·0001), median progression-free survival was 8·1 months (95% CI 6·2-8·8; 214 events occurred) in the cemiplimab group versus 5·3 months (4·3-6·1; 236 events occurred) in the chemotherapy group (HR 0·51, 95% CI 0·42-0·62; p<0·0001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 6·6 months (6·1-9·3) and overall survival of 15·1 months (11·3-18·7). The most common grade 3-4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signals INTERPRETATION: At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer. FUNDING: Regeneron Pharmaceuticals and Sanofi.

Circulating miRNAs as a Tool for Early Diagnosis of Endometrial Cancer-Implications for the Fertility-Sparing Process: Clinical, Biological, and Legal Aspects.

This review article explores the possibility of developing an integrated approach to the management of the different needs of endometrial cancer (EC) patients seeking to become pregnant. Life preservation of the woman, health preservation of the baby, a precocious and-as much as possible-minimally invasive characterization of the health and fertility parameters of the patient, together with the concerns regarding the obstetric, neonatal, and adult health risks of the children conceived via assisted reproductive techniques (ART) are all essential aspects of the problem to be taken into consideration, yet the possibility to harmonize such needs through a concerted and integrated approach is still very challenging. This review aims to illustrate the main features of EC and how it affects the normal physiology of pre-menopausal women. We also focus on the prospect of a miR-based, molecular evaluation of patient health status, including both EC early diagnosis and staging and, similarly, the receptivity of the woman, discussing the possible evaluation of both aspects using a single specific panel of circulating miRs in the patient, thus allowing a relatively fast, non-invasive testing with a significantly reduced margin of error. Finally, the ethical and legal/regulatory aspects of such innovative techniques require not only a risk-benefit analysis; respect for patient autonomy and equitable health care access allocation are fundamental issues as well.

Quality of life with cemiplimab plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: Patient-reported outcomes from phase 3 EMPOWER-Lung 3.

BACKGROUND: EMPOWER-Lung 3, a randomized 2:1 phase 3 trial, showed clinically meaningful and statistically significant overall survival improvement with cemiplimab plus platinum-doublet chemotherapy versus placebo plus chemotherapy for first-line treatment of advanced non-small cell lung cancer. This study evaluated patient-reported outcomes (PROs). METHODS: PROs were assessed at day 1 (baseline), the start of each treatment cycle (every 3 weeks) for the first six doses, and then at start of every three cycles, using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) and Quality of Life-Lung Cancer Module (QLQ-LC13) questionnaires. Prespecified analyses included a longitudinal mixed-effect model comparing treatment arms and a time to definitive clinically meaningful deterioration (TTD) analysis performed for global health status/quality of life (GHS/QoL) and all scales from the questionnaires. Between-arm TTD comparisons were made using a stratified log-rank test and proportional hazards model. RESULTS: A total of 312 patients were assigned to receive cemiplimab plus platinum-doublet chemotherapy and 154 to receive placebo plus chemotherapy; 391 (83.9%) were male and the median age was 63.0 years (range, 25-84). For pain symptoms (EORTC QLQ-C30), a statistically significant overall improvement from baseline (-4.98, 95% confidence interval [CI] -8.36 to -1.60, p = .004) and a statistically significant delay in TTD (hazard ratio, 0.39; 95% CI, 0.26-0.60, p < .0001) favoring cemiplimab plus chemotherapy were observed. Statistically significant delays in TTD, all favoring cemiplimab plus chemotherapy, were also observed in functioning and symptom scales. A significant overall improvement from baseline in GHS/QoL was seen for cemiplimab plus chemotherapy compared with nonsignificant overall change from baseline for placebo plus chemotherapy (1.69, 95% CI, 0.20-3.19 vs. 1.08, 95% CI, -1.34 to 3.51; between arms, p = .673). No analyses yielded statistically significant PRO results favoring placebo plus chemotherapy for any QLQ-C30 or QLQ-LC13 scale. CONCLUSION: Cemiplimab plus chemotherapy resulted in significant overall improvement in pain symptoms and delayed TTD in cancer-related and lung cancer-specific symptoms and functions.

Assisted Reproductive Techniques and Risk of Congenital Heart Diseases in Children: a Systematic Review and Meta-analysis.

Infertility is a growing phenomenon and leads to an increased use of assisted reproductive techniques (ARTs). In recent years, concerns about the safety of these procedures emerged and ARTs were hypothesized to be a risk factor for developing congenital heart diseases (CHDs) in offspring. Our aim is to investigate the association between ART and CHD, specifying results according to various subtypes of defects. We performed a systematic review and random-effects meta-analysis following the PRISMA guidelines. MEDLINE and Google Scholar were searched from January 2011 to May 2022. Data about incidence of CHD in ART were tabulated and extracted from all the studies included. Twenty-four studies were included. Pooled incidence of CHDs after IVF pregnancies was 3% (95% CI 0.3-0.4; I2 = 99%), decreasing to 1% (95% CI 0.00-0.01; I2 = 93%) for major CHDs only. An increased risk of CHDs, especially minor (i.e., not requiring surgical correction), seems to occur in ART compared with non-ART pregnancies [RR 1.71 (95% CI 1.25-2.34; I2 = 99%)]. For major CHDs, not enough evidence is available to assess the real risk. Moreover, some confounding factors (i.e., maternal age and male infertility) seem to play a critical role to determine an increased risk of CHDs. Conflicting results emerged among the studies, setting the need for further research to validate the actual evidence and state the real risk of CHD following ART pregnancies.

Transplacental permeability of heavy metals in relation to newborn sex - evidence from the neurodevelopment project.

Introduction: Gender medicine is an innovative medical approach that studies how some biological variables are influenced by the male or female sex and gender. This issue is under debate because it characterizes the impact of tailored or individual medicine. In this scenario, the aim of this study is to study the correlation between heavy metal exposure and pathologies of neurodevelopment, according to the sex of newborns. In particular, this is an observational study under the name of the Neurosviluppo Project, involving 217 mother-child couples. Material and methods: The correlation with phenotype small for gestational age and congenital malformations were studied, but above all we focused on the pattern of placental permeability to heavy metals. Results: Our results are specifically related to foetal medicine and investigate the impact of foetal sex in transplacental metal exposure. Our results did not show any significant differences related to foetal sex in terms of congenital malformations or the other variables taken into consideration. However, because these conclusions are the first related to the gender medicine in transplacental foetal medicine, they could be a marked background for further studies. Conclusions: Considering the lack of data in literature regarding foetal sexual medicine and transplacental exposure, these study results are pioneering in terms of sexual foetal medicine. Possibly in the future, studies regarding the correlation between foetal sex and obstetrics outcomes will be performed.

Urinary incontinence and quality of life in high-performance swimmers: An observational study.

Each day more women around the world practice high impact physical activities and this may be a risk factor for urinary incontinence (UI) in young. We verified the prevalence of UI and the impact in quality of life (QoL) in high-performance swimmers, through a cross-sectional observational study with 9 high performance swimmers and 9 sedentary women who responded the International Consultation on incontinence Questionnaire - Short Form (ICIQ-SF), participated in a functional evaluation of pelvic floor muscles with bidigital palpation and pad test. We verifed that was present in 78% of high-performance swimmers, and the quality of life was significantly worse (p =.037) when compared to sedentary women. These findings led us to conclude that presence of UI affects the quality of life, even if it is not a factor of abandonment of the sport.

Virtually Augmented Self-Hypnosis in Peripheral Vascular Intervention: A Randomized Controlled Trial.

PURPOSE: Hypnosis is useful for diminishing distress during medical procedures. This study investigated the efficacy of virtually augmented self-hypnosis as an adjunctive non-pharmacological method for procedural pain and anxiety relief during endovascular interventions (EVI). METHODS: We compared an immersive distraction experience (clinicaltrials.gov identifier NCT04561596) featuring virtual reality (VR) using a head-mounted display versus treatment as usual (TAU). Patients followed the "Aqua" module (Oncomfort™) consisting of a scuba dive and breathing exercises. They experienced a self-induced dissociative state similar to clinical hypnosis without direct intervention of a professional. Enrollment followed a 1:1 randomized open study (VR or TAU). Patients' feelings were evaluated just before and after the procedure, and 3 months following intervention. Anxiety was evaluated using the State Trait Anxiety Inventory (STAI) and pain (sensory, emotional, and memory) with a visual analogue scale (VAS). RESULTS: This study included 100 patients. Mean anxiety (pre-post) was significantly reduced within groups and between groups (difference of 4.2 points, p = 0.016). The percentage of responders to anxiety lowering were 76 and 46% for VR and TAU, respectively (p = 0.004). The two groups did not significantly differ in mean sensory-intensity and affective emotional pain (pre-post) using VAS, in negative memories concerning remembered pain at 3 months (difference > 1 from immediate post-procedural reported pain intensity), mean procedural time, or the need for analgesic or sedative drugs. CONCLUSIONS: VR self-hypnosis has the potential to improve the management of patients' distress during radiological procedures. It is safe and effective for reducing anxiety during EVI.

Cemiplimab Plus Chemotherapy Versus Chemotherapy Alone in Advanced NSCLC: 2-Year Follow-Up From the Phase 3 EMPOWER-Lung 3 Part 2 Trial.

INTRODUCTION: EMPOWER-Lung 3 part 2 (NCT03409614), a double-blind, placebo-controlled phase 3 study, investigated cemiplimab (antiprogrammed cell death protein 1) plus chemotherapy versus placebo plus chemotherapy in patients with advanced NSCLC without EGFR, ALK, or ROS1 aberrations, with either squamous or nonsquamous histology, irrespective of programmed death-ligand 1 levels. At primary analysis, after 16.4 months of follow-up, cemiplimab plus chemotherapy improved median overall survival (OS) versus chemotherapy alone (21.9 versus 13.0 mo, hazard ratio [HR] = 0.71, 95% confidence interval [CI]: 0.53-0.93, p = 0.014). Here, we report protocol-specified final OS and 2-year follow-up results. METHODS: Patients (N = 466) were randomized 2:1 to receive histology-specific platinum-doublet chemotherapy, with 350 mg cemiplimab (n = 312) or placebo (n = 154) every 3 weeks for up to 108 weeks. Primary end point was OS; secondary end points included progression-free survival and objective response rates. RESULTS: After 28.4 months of median follow-up, median OS was 21.1 months (95% CI: 15.9-23.5) for cemiplimab plus chemotherapy versus 12.9 months (95% CI: 10.6-15.7) for chemotherapy alone (HR = 0.65, 95% CI: 0.51-0.82, p = 0.0003); median progression-free survival was 8.2 months (95% CI: 6.4-9.0) versus 5.5 months (95% CI: 4.3-6.2) (HR = 0.55, 95% CI: 0.44-0.68, p < 0.0001), and objective response rates were 43.6% versus 22.1%, respectively. Safety was generally consistent with previously reported data. Incidence of treatment-emergent adverse events of grade 3 or higher was 48.7% with cemiplimab plus chemotherapy and 32.7% with chemotherapy alone. CONCLUSIONS: At protocol-specified final OS analysis with 28.4 months of follow-up, the EMPOWER-Lung 3 study continued to reveal benefit of cemiplimab plus chemotherapy versus chemotherapy alone in patients with advanced squamous or nonsquamous NSCLC, across programmed death-ligand 1 levels.

Symptomatic COVID-19 in Pregnancy: Hospital Cohort Data between May 2020 and April 2021, Risk Factors and Medicolegal Implications.

Pregnancy does not appear to increase susceptibility to SARS-CoV-2 infection, but some physiological changes, such as the reduction of residual functional volumes, elevation of the diaphragm, and impaired cellular immunity, may increase the risk of severe disease and result in a higher risk of complications. The article's primary objective is to evaluate the factors associated with symptomatic COVID-19 disease in pregnancy. The secondary objective is to describe maternal and neonatal outcomes and cases of vertical transmission of the infection. All pregnant women hospitalized with SARS-CoV2 infection were included in a prospective study in the UOC of Obstetrics and Gynecology, AOOR Villa Sofia-Cervello, Palermo, between May 2020 and April 2021. The patients who requested the termination of the pregnancy according to Law 194/78 were excluded. We included 165 pregnancies with a total number of 134 deliveries. Overall, 88.5% of the patients were asymptomatic at the time of admission and 11.5% were symptomatic. Of them, 1.8% of the patients required hospital admission in the intensive care unit. Symptoms occurrences were positively associated with the increase in maternal BMI (OR 1.17; p = 0.002), the prematurity (OR 4.71; p = 0.022), and at a lower birth weight (OR 0.99; p = 0.007). One infant tested positive for SARS-CoV2 nasopharyngeal swab; 11.4% of newborns had IgG anti SARS-CoV2 at birth; IgM was positive in 2.4% of newborns. There was no difference statistically significant difference in the vertical transmission of the infection among the group of symptomatic pregnant women and that of asymptomatic pregnant women.

Factors Associated with Anti-SARS-CoV-2 Vaccine Acceptance among Pregnant Women: Data from Outpatient Women Experiencing High-Risk Pregnancy.

Pregnant women are at higher risk of severe Coronavirus disease 2019 (COVID-19) complications than non-pregnant women. The initial exclusion of pregnant women from anti-SARS-CoV-2 vaccines clinical trials has caused a lack of conclusive data about safety and efficacy for this vulnerable population. This cross-sectional study aims to define the factors related to vaccination adherence in a sample of women experiencing high-risk pregnancies. The recruited women completed a questionnaire based on the Health Belief Model. Data were analyzed to evaluate the associations between socio-demographic variables and vaccination acceptance through descriptive, univariate and multivariate logistic analyses. Among the 233 women enrolled, 65.2% (n = 152) declared that they would accept the anti-SARS-CoV-2 vaccine. Multivariate analysis showed that vaccination acceptance was associated with a high educational level (aOR = 4.52, p = 0.001), a low perception of barriers to vaccination (aOR = 1.58, p = 0.005) and the gynecologist's advice (aOR = 3.18, p = 0.01). About a third of pregnant women are still hesitant about the anti-SARS-CoV-2 vaccine, probably because of the conflicting information received from media, friends, acquaintances and health institutions. Determining factors linked to vaccine hesitancy among pregnant women is useful for creating vaccination strategies that increase vaccination uptake.