The Role of Medical Thoracoscopy with Talc Poudrage in Spontaneous, Iatrogenic, and Traumatic Pneumothorax: A Prolonged Experience of a Tertiary Care Center.

INTRODUCTION: Medical thoracoscopy is a minimally invasive and safe procedure mostly performed for unexplained exudative pleural effusions but may be considered for pneumothorax (PNX). METHODS: This retrospective study included participants affected by PNX who underwent medical thoracoscopy with talc poudrage at a single academic hospital from 2008 to 2021. The primary endpoint was the observation of complete radiographical lung re-expansion and absence of air supply from the chest drain within 7 days of medical thoracoscopy. The secondary endpoint was achieving no recurrence of ipsilateral PNX at 24 months post-discharge. RESULTS: A total of 95 patients affected by primary spontaneous PNX (PSP), secondary spontaneous PNX (SSP), iatrogenic, and traumatic PNX were enrolled. An additional procedure was required by 17.89% of patients, and only one patient with SSP required subsequent surgery. Recurrence of PNX occurred on the same side within 24 months after discharge in 9.47% of patients, with a median time to recurrence of 13.5 months. The PSP group was significantly more likely to achieve the primary endpoint. Pleural morphology was significantly associated with reaching the primary endpoint, while receiving a cumulative dose of talc greater than or equal to 4 g during hospitalization was associated with a lower risk of meeting it. Receiving a cumulative dose of talc greater than or equal to 4 g led in all cases to the achievement of the secondary endpoint. Patients with iatrogenic and traumatic PNX had an excellent prognosis in both the short- and long-term evaluation. CONCLUSION: Medical thoracoscopy is an effective procedure for treating PNX in the acute setting in selected cases while preventing long-term relapses. Large prospective clinical studies are needed to support and better define the role of medical thoracoscopy in current clinical practice.

A systematic review of non-coding RNA therapeutics in early clinical trials: a new perspective against cancer.

Targeting non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), has recently emerged as a promising strategy for treating malignancies and other diseases. In recent years, the development of ncRNA-based therapeutics for targeting protein-coding and non-coding genes has also gained momentum. This review systematically examines ongoing and completed clinical trials to provide a comprehensive overview of the emerging landscape of ncRNA-based therapeutics. Significant efforts have been made to advance ncRNA therapeutics to early clinical studies. The most advanced trials have been conducted with small interfering RNAs (siRNAs), miRNA replacement using nanovector-entrapped miRNA mimics, or miRNA silencing by antisense oligonucleotides. While siRNA-based therapeutics have already received FDA approval, miRNA mimics, inhibitors, and lncRNA-based therapeutics are still under evaluation in preclinical and early clinical studies. We critically discuss the rationale and methodologies of ncRNA targeting strategies to illustrate this rapidly evolving field.

Non-surgical retreatment versus papillary preservation flap surgery for residual pockets: A randomized controlled trial with clinical and patient-reported outcomes.

AIM: To compare the efficacy of non-surgical re-instrumentation (NSR) and papillary preservation flap (PPF) surgery at single-rooted teeth with residual pockets. MATERIALS AND METHODS: Patients with at least a residual pocket depth (PD ≥ 5 mm) after Steps I and II were enrolled and randomly assigned to receive NSR or PPF surgery. The primary outcome was PD reduction, and secondary outcomes were clinical attachment level (CAL) change and patient-reported outcome measures (PROMs). Outcome variables were measured at baseline, 3 and 6 months. The examiner was blinded. Statistical analysis, one site for each patient, included descriptive statistics and analysis of covariance. RESULTS: Forty-six participants were enrolled, and one patient dropped out in the PPF group. After 6 months, both treatments resulted in significant PD reduction (1.3 ± 1.2 mm, p = .009 NSR; 2.0 ± 0.7 mm, p < .001 PPF) and CAL gain (1.0 ± 2.4 mm, p = .031 NSR; 1.4 ± 0.8 mm, p < .001 PPF). PD reduction between groups was not statistically significant (diff: 0.6 mm; 95% confidence interval [CI] [-0.3 to 1.5]; p = .167). Pocket closure was 61% NSR versus 86% PPF (p = .091). Smoking was associated with less PD reduction of almost 1 mm in both treatments. Treatment time was longer for PPF surgery, but PROMs and post-operative pain were similar between groups. CONCLUSIONS: Both NSR and PPF reduced PD without significant difference between treatments at 6 months. PPF surgery may offer faster PD reduction, but smoking habits reduce treatment efficacy.

Case-by-case combination of the prostate imaging reporting and data system version 2.1 with the Likert score to reduce the false-positives of prostate MRI: a proof-of-concept study.

OBJECTIVES: To retrospectively investigate whether a case-by-case combination of the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS) with the Likert score improves the diagnostic performance of mpMRI for clinically significant prostate cancer (csPCa), especially by reducing false-positives. METHODS: One hundred men received mpMRI between January 2020 and April 2021, followed by prostate biopsy. Reader 1 (R1) and reader 2 (R2) (experience of > 3000 and < 200 mpMRI readings) independently reviewed mpMRIs with the PI-RADS version 2.1. After unveiling clinical information, they were free to add (or not) a Likert score to upgrade or downgrade or reinforce the level of suspicion of the PI-RADS category attributed to the index lesion or, rather, identify a new index lesion. We calculated sensitivity, specificity, and predictive values of R1/R2 in detecting csPCa when biopsying PI-RADS ≥ 3 index-lesions (strategy 1) versus PI-RADS ≥ 3 or Likert ≥ 3 index-lesions (strategy 2), with decision curve analysis to assess the net benefit. In strategy 2, the Likert score was considered dominant in determining biopsy decisions. RESULTS: csPCa prevalence was 38%. R1/R2 used combined PI-RADS and Likert categorization in 28%/18% of examinations relying mainly on clinical features such as prostate specific antigen level and digital rectal examination than imaging findings. The specificity/positive predictive values were 66.1/63.1% for R1 (95%CI 52.9-77.6/54.5-70.9) and 50.0/51.6% (95%CI 37.0-63.0/35.5-72.4%) for R2 in the case of PI-RADS-based readings, and 74.2/69.2% for R1 (95%CI 61.5-84.5/59.4-77.5%) and 56.6/54.2% (95%CI 43.3-69.0/37.1-76.6%) for R2 in the case of combined PI-RADS/Likert readings. Sensitivity/negative predictive values were unaffected. Strategy 2 achieved greater net benefit as a trigger of biopsy for R1 only. CONCLUSION: Case-by-case combination of the PI-RADS version 2.1 with Likert score translated into a mild but measurable impact in reducing the false-positives of PI-RADS categorization, though greater net benefit in reducing unnecessary biopsies was found in the experienced reader only.

Public cancer screening services and participation: What meanings in users' narratives to promote engagement?

Despite the effectiveness of cancer screening (CS) in providing timely diagnoses and early treatments, the participation of citizens remains very low in particular in Southern Italy. This study aims to investigate the meanings that intervene in the relationship between the individual and their active participation in CSs within public healthcare. A total of 101 ad hoc semi-structured interviews were collected with CS users in public service of Campania Region, Italy. The interviews were analyzed through a qualitative-quantitative methodology by T-Lab software. A cluster analysis and multiple matching analysis were conducted. Findings show five clusters: prevention as a sensory and emotional burden; prevention as a strategy to manage the hereditary risk of death; individual's internal demand for health; the times and places of prevention; and the concreteness of doing prevention; and two factors: from the risk of disease diagnosis to preventive measures and from external healthcare settings to internal self-care settings. Findings shed light on how to construct better well-being promotion strategies and foster a subjective health and prevention demand accounting for the continuous experiences of those participating in CSs to encourage greater citizen engagement.

LNA-i-miR-221 activity in colorectal cancer: A reverse translational investigation.

Colorectal cancer (CRC) is one of the most common malignancies and a relevant cause of cancer-related deaths worldwide. Dysregulation of microRNA (miRNA) expression has been associated with the development and progression of various cancers, including CRC. Among them, miR-221 emerged as an oncogenic driver, whose high expression is associated with poor patient prognosis. The present study was conceived to investigate the anti-CRC activity of miR-221 silencing based on early clinical data achieved from a first-in-human study by our group. Going back from bedside to bench, we demonstrated that LNA-i-miR-221 reduces cell viability, induces apoptosis in vitro, and impairs tumor growth in preclinical in vivo models of CRC. Importantly, we disclosed that miR-221 directly targets TP53BP2, which, together with TP53INP1, is known as a positive regulator of the TP53 apoptotic pathway. We found that (1) both these genes are overexpressed following miR-221 inhibition, (2) the strong anti-tumor activity of LNA-i-miR-221 was selectively observed on TP53 wild-type cells, and (3) this activity was reduced in the presence of the TP53-inhibitor Pifitrin-α. Our data pave the way to further investigations on TP53 functionality as a marker predictive of response to miR-221 silencing, which might be relevant for clinical applications.

Identification of ADME genes polymorphic variants linked to trastuzumab-induced cardiotoxicity in breast cancer patients: Case series of mono-institutional experience.

BACKGROUND: Long-term survival induced by anticancer treatments discloses emerging frailty among breast cancer (BC) survivors. Trastuzumab-induced cardiotoxicity (TIC) is reported in at least 5% of HER2+BC patients. However, TIC mechanism remains unclear and predictive genetic biomarkers are still lacking. Interaction between systemic inflammation, cytokine release and ADME genes in cancer patients might contribute to explain mechanisms underlying individual susceptibility to TIC and drug response variability. We present a single institution case series to investigate the potential role of genetic variants in ADME genes in HER2+BC patients TIC experienced. METHODS: We selected data related to 40 HER2+ BC patients undergone to DMET genotyping of ADME constitutive variant profiling, with the aim to prospectively explore their potential role in developing TIC. Only 3 patients ("case series"), who experienced TIC, were compared to 37 "control group" matched patients cardiotoxicity-sparing. All patients underwent to left ventricular ejection fraction (LVEF) evaluation at diagnosis and during anti-HER2 therapy. Each single probe was clustered to detect SNPs related to cardiotoxicity. RESULTS: In this retrospective analysis, our 3 cases were homogeneous in terms of clinical-pathological characteristics, trastuzumab-based treatment and LVEF decline. We identified 9 polymorphic variants in 8 ADME genes (UGT1A1, UGT1A6, UGT1A7, UGT2B15, SLC22A1, CYP3A5, ABCC4, CYP2D6) potentially associated with TIC. CONCLUSION: Real-world TIC incidence is higher compared to randomized clinical trials and biomarkers with potential predictive value aren't available. Our preliminary data, as proof of concept, could suggest a predictive role of pharmacogenomic approach in the identification of cardiotoxicity risk biomarkers for anti-HER2 treatment.

Recipient hepatectomy technique may affect oncological outcomes of liver transplantation for hepatocellular carcinoma.

To date, caval sparing (CS) and total caval replacement (TCR) for recipient hepatectomy in liver transplantation (LT) have been compared only in terms of surgical morbidity. Nonetheless, the CS technique is inherently associated with an increased manipulation of the native liver and later exclusion of the venous outflow, which may increase the risk of intraoperative shedding of tumor cells when LT is performed for HCC. A multicenter, retrospective study was performed to assess the impact of recipient hepatectomy (CS vs. TCR) on the risk of posttransplant HCC recurrence among 16 European transplant centers that used either TCR or CS recipient hepatectomy as an elective protocol technique. Exclusion criteria comprised cases of non-center-protocol recipient hepatectomy technique, living-donor LT, HCC diagnosis suspected on preoperative imaging but not confirmed at the pathological examination of the explanted liver, HCC in close contact with the IVC, and previous liver resection for HCC. In 2420 patients, CS and TCR approaches were used in 1452 (60%) and 968 (40%) cases, respectively. Group adjustment with inverse probability weighting was performed for high-volume center, recipient age, alcohol abuse, viral hepatitis, Child-Pugh class C, Model for End-Stage Liver Disease score, cold ischemia time, clinical HCC stage within Milan criteria, pre-LT downstaging/bridging therapies, pre-LT alphafetoprotein serum levels, number and size of tumor nodules, microvascular invasion, and complete necrosis of all tumor nodules (matched cohort, TCR, n = 938; CS, n = 935). In a multivariate cause-specific hazard model, CS was associated with a higher risk of HCC recurrence (HR: 1.536, p = 0.007). In conclusion, TCR recipient hepatectomy, compared to the CS approach, may be associated with some protective effect against post-LT tumor recurrence.

Polynucleotides and Hyaluronic Acid (PN-HA) Mixture With or Without Deproteinized Bovine Bone Mineral as a Novel Approach for the Treatment of Deep Infra-Bony Defects: A Retrospective Case-Series.

Polynucleotides and Hyaluronic Acid (PN-HA) mixture showed several effects in modulation of healing process. The aim of this study was to assess the safety and clinical performance of PN-HA alone or in association with Deproteinized Bovine Bone Mineral (DBBM) with papillary preservation flaps (PPF) in the treatment of residual pockets. A total of 43 patients with 55 infra-bony defects were recruited; 30% were smokers. The mean baseline Probing Depth (PD) was 7.7 ±1.9 mm with a corresponding mean recession (Rec) of 1.9± 1.3 mm. The depth of infra-bony defect at the surgical measurement was 5.2±2.1 mm. DBBM was applied at 56% of the defects considered as not-containing based on clinical judgment. Healing was uneventful at all sites. After one year, PD reduction was 4.4±1.8 mm with a Rec increase of 1.0 ±0.8 mm. Detected bone fill at x-ray was 3.5 ± 1.9mm. The multilevel analysis showed that absence of smoking habits was associated with improved PD reduction (P =0.026) and bone gain (P= 0.039). PN-HA mixture is a safe product for periodontal surgery and seems to promote clinical benefit in the treatment of residual pockets associated to infra-bony defects.

Users' Experience of Public Cancer Screening Services: Qualitative Research Findings and Implications for Public Health System.

Following the One Health approach, designing multidimensional strategies to orient healthcare in promoting health and preventive processes has become paramount. In particular, in the prevention domain, cancer screening attendance is still unsatisfactory in many populations and requires specific consideration. To this end, following a research-intervention logic, this study aims to investigate the experiences and meanings that users of public cancer screening services associate with prevention, particularly participation in the screenings. The experiences of 103 users (96 females; Mage = 54.0; SD = 1.24) of public cancer screening programs in the Campania region (Italy) were collected through interviews. The data collected were analysed following the Grounded Theory Methodology, supported by the software Atlas.ti 8.0. The text material was organised into eight macro-categories: Health and Body; Relationship with Cancer and Diseases; Health Facilities and Health Providers; The Affective Determinants of Cancer Screening Participation; Partners and Children; Physical Sensations and Emotions in the Course of Action; Protective Actions; Promotion and Dissemination. The core category was named Family and Familiarity. Respondents perceived prevention as an act of care for the family and themselves. Our findings support a shift from the idea of taking care of personal health as an individual matter toward considering it as a community issue, according to which resistance to act is overcome for and through the presence of loved ones. The results of this study contribute to a deeper understanding of the perspectives of southern Italian users on participation in cancer screening, and provide important insights to guide future actions to promote these public programmes based primarily on the emerging theme of family and familiarity related to screening programs.

A New Method for Selective Extraction of Torularhodin from Red Yeast Using CO2-SFE Technique.

Torularhodin is a dark pink colored carotenoid belonging to the xanthophylls group that can be biologically synthesized by red yeasts, especially by Rhodotorula and Sporobolomyces genera. The growing interest in this molecule is due to its biological activities such as antioxidant, anticholesterolemic, anti-inflammatory, antimicrobial, and anticancer. To satisfy potential commercial markets, numerous methods have been proposed to develop a cost-effective and environmentally friendly downstream process for the purification of torularhodin. However, obtaining high purity products without resorting to the use of toxic solvents, which can leave residues in the final preparations, remains a major challenge. In this context, the present study aimed to develop a new efficient method for the isolation of torularhodin from the red yeast Rhodotorula strain ELP2022 by applying the extraction technique with supercritical CO2 (CO2-SFE) in two sequential steps. In particular, in the first step, the dried lysed biomass of yeast was subjected to the action of CO2 in supercritical conditions (CO2SC) as sole solvent for extraction of apolar carotenoids. In the second step, the residual biomass was subjected to the action of CO2SC using ethanol as a polar co-solvent for the extraction of torularhodin. Both steps were carried out at different operating parameters of temperature (40 and 60 °C) and pressure (from 300 to 500 bar) with a constant CO2 flow of 6 L min-1. Regardless of the operating conditions used, this method allowed to obtain an orange-colored oily extract and a red-colored extract after the first and second step, respectively. In all trials, torularhodin represented no less than 95.2% ± 0.70 of the total carotenoids in the red extracts obtained from the second step. In particular, the best results were obtained by performing both steps at 40 °C and 300 bar, and the maximum percentage of torularhodin achieved was 97.9% ± 0.88. Since there are no data on the selective recovery of torularhodin from red yeast using the SFE technique, this study may be a good starting point to optimize and support the development of industrial production of torularhodin by microbial synthesis. This new method can significantly reduce the environmental impact of torularhodin recovery and can be considered an innovation for which an Italian patent application has been filed. In a circular bioeconomy approach, this method will be validated up to a pilot scale, culturing the strain Rhodotorula spp. ELP2022 on low-cost media derived from agri-food wastes.

UMG1/CD3ε-bispecific T-cell engager redirects T-cell cytotoxicity against diffuse large B-cell lymphoma.

UMG1 is a unique epitope of CD43, not expressed by normal cells and tissues of haematopoietic and non-haematopoietic origin, except thymocytes and a minority (<5%) of peripheral blood T lymphocytes. By immunohistochemistry analysis of tissue microarray and pathology slides, we found high UMG1 expression in 20%-24% of diffuse large B-cell lymphomas (DLBCLs), including highly aggressive BCL2high and CD20low cases. UMG1 membrane expression was also found in DLBCL bone marrow-infiltrating cells and established cell lines. Targeting UMG1 with a novel asymmetric UMG1/CD3ε-bispecific T-cell engager (BTCE) induced redirected cytotoxicity against DLBCL cells and was synergistic with lenalidomide. We conclude that UMG1/CD3ε-BTCE is a promising therapeutic for DLBCLs.

Emotions and Narrative Reappraisal Strategies of Users of Breast Cancer Screening: Reconstructing the Past, Passing Through the Present, and Predicting Emotions.

Emotional forecasting, meaning how a person anticipates feeling as a consequence of their choices, drives healthcare decision-making. Research, however, suggests that people often do not fully anticipate or otherwise grasp the future emotional impacts of their decisions. Emotional reappraisal strategies, such as putting emotions into words and sharing emotions with others, may mitigate potential undesirable effects of emotions on decision-making. The use of such strategies is important for consequential decisions, such as obtaining timely mammography screening for breast cancer, whereby earlier diagnosis may impact the success of treatment. In this study, we explored the use of emotional reappraisal strategies for decision-making regarding breast cancer screening attendance among women aged 50-69 years. Data were collected through semi-structured interviews following mammography with a reflexive thematic methodological approach employed for analysis. Results shed light on how participants' emotional response narratives were reconstructed before the mammography, felt during the mammography, and forecasted while awaiting the results. Future research should consider how individuals experience and manage their emotions as they access breast screening services.

Extracellular vesicle features are associated with COVID-19 severity.

COVID-19 is heterogeneous; therefore, it is crucial to identify early biomarkers for adverse outcomes. Extracellular vesicles (EV) are involved in the pathophysiology of COVID-19 and have both negative and positive effects. The objective of this study was to identify the potential role of EV in the prognostic stratification of COVID-19 patients. A total of 146 patients with severe or critical COVID-19 were enrolled. Demographic and comorbidity characteristics were collected, together with routine haematology, blood chemistry and lymphocyte subpopulation data. Flow cytometric characterization of the dimensional and antigenic properties of COVID-19 patients' plasma EVs was conducted. Elastic net logistic regression with cross-validation was employed to identify the best model for classifying critically ill patients. Features of smaller EVs (i.e. the fraction of EVs smaller than 200 nm expressing either cluster of differentiation [CD] 31, CD 140b or CD 42b), albuminemia and the percentage of monocytes expressing human leukocyte antigen DR (HLA-DR) were associated with a better outcome. Conversely, the proportion of larger EVs expressing N-cadherin, CD 34, CD 56, CD31 or CD 45, interleukin 6, red cell width distribution (RDW), N-terminal pro-brain natriuretic peptide (NT-proBNP), age, procalcitonin, Charlson Comorbidity Index and pro-adrenomedullin were associated with disease severity. Therefore, the simultaneous assessment of EV dimensions and their antigenic properties complements laboratory workup and helps in patient stratification.

Stem Cells mobilization and collection in allogeneic related and unrelated donors: a single center experience with focus on plerixafor.

INTRODUCTION: Poor CD34 + cells mobilization in allogeneic donors could affect transplant outcome. In a subgroup of patient mobilization with granulocyte colony-stimulating factor (G-CSF) alone is unsatisfactory, and Plerixafor could be used to enhance CD34 + cells release from bone marrow niche. MATERIALS AND METHODS: We conducted a retrospective single-center, cohort study on healthy allogeneic donors both related and unrelated, treated by Udine Transfusion Center over the last 10 years (2012-2022). In the 195 allogeneic donors treated we analyzed age, sex, body weight, BMI, comorbidities, G-CSF dosage and even baseline white blood cell count as possible predictor of insufficient CD34 + cells mobilization on day 5. In the subgroup of related donors we evaluated even baseline CD34 + cells (measured before mobilization start). Processed donor blood volume, collection efficiency and apheresis product were examined. Additionally a comparative analysis was conducted between G-CSF alone treated donors and poor mobilizing ones, in which Plerixafor was administered at a dose of 0.24 mg/kg as a pre-emptive or rescue agent. RESULTS: In 9 donors, due to poor mobilization (defined as CD34 + < 20/µL or estimated yield < 1 ×106 kg/recipient body weight), the use of plerixafor was necessary. PLX at a dose of 0.24 mg/kg was administered 5 h before collection, inducing an average increase of 5.1 (1.7-12.6) in CD34 + circulating cells. In this subgroup of patients, BMI and weight were significantly lower (p = 0.03). Interestingly, baseline CD34 + cells (measured before the onset of mobilization) also seems to predict poor mobilization (p = 0.003). In donors additionally treated with Plerixafor compared to those who received G-CSF alone, collection efficiency was higher (p = 0.02) and CD34 + cells collected were comparable (p = 0.2). Side effects related to the administration of plerixafor, if they occurred, were well tolerated. CONCLUSIONS: Plerixafor is a safe and effective drug in the rescue and prevention of poor mobilization. New prospective studies on allogeneic donors should be performed to increase the treatable population to avoid inadequate collection and mobilization. New laboratory predictors such as baseline CD34 + cells should be investigated in larger cohorts and then used as early screening.

Eosinophil Cationic Protein Variation in Patients with Asthma and CRSwNP Treated with Dupilumab.

BACKGROUND: Asthma is a clinical syndrome characterized by recurrent episodes of airway obstruction, bronchial hyperresponsiveness and airway inflammation. Most patients with asthma present a "type 2" (TH2) inflammation. ILC2 and TH2 cells release cytokines IL4, IL-13 and IL-5. CRSwNP is a condition characterized by hyposmia or anosmia, nasal congestion, nasal discharge, and face pain or pressure that last for at least 12 weeks in a row without relief. Both asthma and CRSwNP are often characterized by a type 2 inflammation endotype and are often present in the same patient. Dupilumab is a fully human monoclonal antibody targeting the interleukin-4 receptor α (IL-4Rα) subunit, blocking IL4/IL-4Rα binding and IL13. It has been labelled for the treatment of moderate to severe asthma in patients from the age of 12 years with an eosinophilic phenotype, and it has demonstrated efficacy and acceptable safety. Our study aims to investigate the effects of dupilumab on type 2 inflammatory biomarkers, such as eosinophils and eosinophil cationic protein (ECP). ECP is an eosinophil-derived substance contained in granules that are released during inflammation and causes various biological effects, including tissue damage in asthmatic airways. METHODS: ECP, Eosinophil counts (EOS), and total immunoglobulin E (IgE) levels were longitudinally measured using immunoassays in the serum of 21 patients affected by CRSwNP, of which 17 had asthma as a comorbidity, receiving 300 mg dupilumab every two weeks. RESULTS: The EOS and ECP, after a first phase of significant increase due to the intrinsic characteristic of the block of IL-4 and IL-13, returned to the baseline 10 months after the initial administration of dupilumab. Fractional exhaled nitric oxide (FeNO) and serum total IgE decreased significantly after 9 months. Asthma Control Test (ACT) scores improved after dupilumab treatment. FEV1% and FEV1 absolute registered a significant improvement at 10 months. CONCLUSIONS: Patients who received 300 milligrams of dupilumab every two weeks first experienced a temporary increase in eosinophils (EOS) and eosinophil cationic protein (ECP), then exhibited a gradual decline in these variables with a subsequent return to the initial baseline levels. When compared to the baseline, we observed that the levels of IgE and FeNO decreased over time, while there was an increase in both FEV1 and FEV1%.

Influence of a regional network combined with a systematic multidisciplinary approach on the outcomes of patients with acute type A aortic dissection.

BACKGROUND: Whether in patients with acute type A aortic dissection reduction of intervals between onset of symptoms and diagnosis influences patient outcomes is still not completely defined. METHODS: In 199 patients with acute type A aortic dissection, the efficacy of a systematic multidisciplinary approach and institution of a regional network were evaluated; 90 patients operated before 2016 (Group1) were compared with 109 repaired after 2016 (Group2) for early and late outcomes. RESULTS: Mortality was reduced from 13% in Group1 to 4% in Group2 (p = 0.013). In Group2 a more patients (46%) had arch replacement compared to Group1 (29%)(p = 0.06). In Group2 axillary artery cannulation was almost routinely used (91% vs 67%, p < 0.001) with shorter circulatory arrest time (37 vs 44 min, p < 0.001). The interval from diagnosis to surgery dropped from 210 min in Group1 to 160 min in Group2 (p < 0.001); this reduction was evident both in patients admitted to the emergency department of a spoke and/or a hub center. Patients presenting with or developing shock were reduced from Group1 to Group2 and in particular those reaching the hub center from spoke centers. Survival at 1 and 5 years was 82 ± 4% and 70 ± 5% in Group1 vs 92 ± 3% and 87 ± 8% in Group2 (p = 0.007). CONCLUSIONS: Outcomes of patients with acute type A aortic dissection improved using a systematic multidisciplinary approach while a network between spoke and hub centers reduced intervals between diagnosis, transportation to hub center and repair, limiting the incidence of tamponade and shock.

Effect of Visual Booklets to Improve Bowel Preparation in Colonoscopy: Systematic Review with Meta-Analysis.

An optimal bowel preparation for colonoscopy is essential to increasing the quality of the examination. Visual booklets have been proposed with conflicting results to enhance bowel preparation. A literature search was performed in March 2023 in the most important databases. Only RCTs were selected. We calculated odd ratios (OR) for dichotomous outcomes. Mean differences (MD) or standardized mean differences (SMD) were used for continuous outcomes. We estimated heterogeneity with the Chi2 and the I2 statistics. In cases of high heterogeneity, a random effect model was used. Six studies were selected, enrolling 1755 patients overall. Adequate bowel preparation was observed in 86.7% of the booklet group versus 77.5% of the control group, with an OR = 2.31 in favor of the booklet. In studies using a 4-L PEG-based preparation, no difference compared to controls was observed, while in non-PEG formulations, preparation with booklets was better than in controls (OR = 5.10, 95% CI 1.82-14.27, p = 0.002). Two studies were performed in an inpatient setting without any differences between booklets and controls, while outpatients receiving booklets had better results (OR = 7.13, 95% CI 5.39-9.45, p < 0.001). The adenoma detection rate was similar between the two groups. In conclusion, booklets are useful to improve bowel preparation. Outpatient settings and preparations not containing PEG could benefit more from booklets.

Hit identification of novel small molecules interfering with MALAT1 triplex by a structure-based virtual screening.

Nowadays, RNA is an attractive target for the design of new small molecules with different pharmacological activities. Among several RNA molecules, long noncoding RNAs (lncRNAs) are extensively reported to be involved in cancer pathogenesis. In particular, the overexpression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays an important role in the development of multiple myeloma (MM). Starting from the crystallographic structure of the triple-helical stability element at the 3'-end of MALAT1, we performed a structure-based virtual screening of a large commercial database, previously filtered according to the drug-like properties. After a thermodynamic analysis, we selected five compounds for the in vitro assays. Compound M5, characterized by a diazaindene scaffold, emerged as the most promising molecule enabling the destabilization of the MALAT1 triplex structure and antiproliferative activity on in vitro models of MM. M5 is proposed as a lead compound to be further optimized for improving its affinity toward MALAT1.