Mohs micrographic technique in high-risk basal cell carcinoma: a 3D prediction of safety margins.

OBJECTIVE: Compared with standard excision with a two-dimensional histological examination, Mohs micrographic surgery offers a lower recurrence rate and a greater extent of healthy tissue sparing for the treatment of high-risk basal cell carcinoma (BCC). The aims of this study were to first quantify the healthy tissue spared through the micrographic technique compared to traditional surgery for high-risk tumours. Then, to speculate, through the analysis of the distal micrographic resection margin, the adequate width of safety margins for standard excision. METHOD: A cohort of patients with high-risk BCC was treated with Mohs surgery. Safety margins, tumours residual final breach and hypothetical standard excision safety margins areas were recorded. RESULTS: A total of 96 patients were included. A reduction of 27.96% (95% Confidence Interval (CI): 17.90-38.02) of healthy skin removed was observed using a micrographic method compared to the standard approach. Standard excision with a 6mm safety margin was associated with 86.46% (95% CI: 79.62-93.30) of complete excision. Greater margins were not associated with a statistically significant improvement of complete excision. CONCLUSION: Mohs surgery should be considered the gold standard operative treatment for high-risk BCC. However, if micrographic techniques are not feasible, the standard excision with a predetermined margin of 6 mm, should be considered as the best option.

Superb microvascular imaging (SMI) and elastosonography in thyroid nodule: diagnostic value in a real-time cohort.

PURPOSE: In clinical practice, thyroid nodules are classified according to TI-RADS by B-mode and color-flow Doppler study. The aim of the study is to evaluate the possible added value of Superb microvascular imaging (SMI) and elastosonography in the stratification of malignancy risk of thyroid nodules. METHODS: All patients with thyroid nodules who were candidates for needle aspiration were enrolled. Experienced operators performed a standard examination with TI-RADS calculation, followed by SMI and elastosonography on the nodules. The needle aspiration outcome was used as the gold standard. Statistical analysis calculated the ROC curves of the techniques applied individually and serially. RESULTS: In this prospective study, we analysed 260 nodules, found in 251 patients (mean age 58.6 yo ± 14). 11.2% were TI-RADS 1, 18.9% TI-RADS 2, 41.1% TI-RADS 3, 28.1% TI-RADS 4, and 0.8% TI-RADS 5. The SMI technique showed an AUC of 0.57 (95% CI 0.49; 0.66) while elastosonography had an AUC of 0.58 (95% CI 0.49; 0.67) when used individually. SMI together with elastosonography had AUC of 0.62 (95% CI 0.52; 0.71). TI-RADS had AUC of 0.67 (95% CI 0.59; 0.75). SMI and elastosonography applied together with TI-RADS had AUC of 0.69 (95% CI 0.61; 0.77). CONCLUSION: In the real-world cohort of patients, the SMI technique and elastosonography slightly increase the AUC of TI-RADS. Taken individually, SMI and elastosonography do not have a very strong AUC.

Human papillomavirus genotyping in high-grade vaginal intraepithelial neoplasia: A multicentric Italian study.

This study aimed to analyze the human papillomavirus (HPV) genotype distribution in a large cohort of high-grade vaginal intraepithelial neoplasia (VaIN) (vaginal HSIL, VaIN2/3) patients from two Italian referral centers. We included all patients with histologically confirmed VaIN2/3 from the Department of Surgical Sciences, Sant'Anna Hospital, University of Torino, Torino, Italy, and Ospedale Maggiore della Carità, Novara, Italy, between 2003 and 2022. After the histological evaluation of formalin-fixed paraffin-embedded samples, we performed HPV genotyping with VisionArray HPV Chip 1.0. We detected HPV DNA in 94.4% of VaIN2/3 (168/178), with HPV 16 as the most prevalent genotype, accounting for 51.8% of all infections, 41.2% of VaIN2 and 77.6% of VaIN3 cases. Other frequent genotypes were HPV 58 (8.3%, 10.9% of VaIN2 and 2.0% of VaIN3), HPV 73 (5.4%, 5.0% of VaIN2 and 6.1% of VaIN3), and HPV 31 (5.4%, 6.7% of VaIN2 and 2.0% of VaIN3). 73.2% of VaIN2/3 had a single HPV genotype infection and 26.8% a multiple infection (20.8% a double infection, 4.8% a triple infection, and 1.2% a quadruple infection). Single infection was more frequently present in VaIN3 than VaIN2 (81.6% vs. 69.8%). 69.1% of single infections and 73.3% of multiple infections had one or more genotypes covered by nine-valent HPV vaccine. HPV vaccination is expected to have a large impact on reducing the incidence of vaginal intraepithelial neoplasia.

Epidemiology and risk factors for multiple squamous cell carcinomas in a cohort of organ transplant recipients from northern Italy: a single center study.

BACKGROUND: Keratinocyte cancers account for the most frequent oncological complication in organ transplant recipients. To date, many different risk factors have been reported, unless variability among the studies exist. We aimed to determine the incidence and risk factors for keratinocyte neoplasms in a cohort of kidney transplant and liver transplant recipients. METHODS: A cohort of 338 patients were included in this retrospective study and followed-up from transplantation until the end of December 2021, with a 2-year minimum transplant time. Each skin cancer was collected in a specific database, together with all the demographic data and dermatological history and feature of patients. RESULTS: In our cohort, liver transplant patients presented a higher keratinocyte cancer incidence compared to kidney transplant recipients. Regarding the risk factors for skin cancer in the entire group of patients, we observed a significant association with the detection of actinic keratosis and solar lentigo, and such relation was stronger when considering patients developing multiple skin cancers, in which fair skin types and occupational sun exposure were also associated. Furthermore, while actinic keratosis and a history of previous dialysis were significantly associated with the development of a least one squamous cell carcinoma, the presence of keratotic lesions and azathioprine intake resulted connected with the appearance of multiple squamous neoplasms. CONCLUSIONS: We report here that, in our cohort, factors potentially leading to immune dysfunction were found to play a causative role in the development of the more aggressive histotype of keratinocyte tumors, and such association seemed more convincing in case of multiple squamous cell carcinomas.

Aquaporin 1, Aquaporin 8, and Aquaporin 9 Expressions in Malignant Melanoma: A Possible Correlation with Prognosis and Clinical Outcome.

Aquaporins (AQPs) are small transmembrane proteins able to facilitate the passive transport of water and small molecules throughout cells. Several studies have demonstrated that modulation of AQPs' expression contributes to cancer development and progression. However, to date, very little is known about their involvement in malignant melanoma (MM) progression. In this retrospective observational study, we evaluated the correlation between AQP1, -8, and -9 expression and the clinical outcomes of 58 patients diagnosed with MM from 2014 to 2016, of which 14 were diagnosed as nodular melanoma (NM) and 44 as superficial spreading melanoma (SSM). In general, we found that AQPs were more highly expressed in SSM than NM, suggesting a potential correlation with prognosis. While analyzing the expression of each AQP, we discovered that AQP1 was associated with a specific body site and low mitotic index, AQP8 with a negative sentinel lymph node, and AQP9 with the Breslow thickness and lack of ulcerations. Together with the survival analysis performed in this study, our results suggest that the expression of AQP1, -8, and -9 could be correlated with a better prognosis for malignant melanoma.

Laparoscopic Sleeve Gastrectomy in Patients Over 60 Years Old: A Long-Term Follow-Up.

Purpose: This study analyzed the safety and effectiveness of laparoscopic sleeve gastrectomy (LSG) in patients over 60 years old, in a long-term follow-up, in a high-volume bariatric center. Methods: We retrospectively analyzed all patients older than 60 years who underwent LSG in our center from January 2009 to December 2018. A prospectively collected database of 4991 consecutive LSG cases was reviewed. Results: One hundred seventy-nine sleeve gastrectomy procedures were performed in patients older than 60 years, 135 were aged 60-65 years (group A) and 44 were older than 65 years (group B). We reported five cases (2.7%) of early complications: three postoperative hemorrhages, one cardial leakage, and one perigastric abscess. No thromboembolic events or mortality rates were reported. The mean follow-up period was 5.5 years (66 months). The follow-up loss rate was about 29%. At last follow-up, the mean body-mass index/body mass/percentage of excess weight loss values were, respectively, 33.7 ± 7/86.1 ± 21/60.4 ± 28.6 in group A and 32.4 ± 6.4/82.6 ± 18/61.8 ± 33 in group B. We reported 5 (4.0%) trocar site hernias, 1 (0.8%) cardial junction stenosis, and 22 (18%) new outbreaks of gastroesophageal reflux (GERD). There were 7 reinterventions (5.7%): 5 for weight regain and 2 for GERD not responding to medical therapy. There were no statistically significant differences between the two age groups. Conclusions: LSG is a safe and effective treatment for severe obesity in people over 60 years old. There are no differences in results of patients over 65 years and between 60 and 65 years old. Scales that include associated medical problems and the patient's general condition must be considered.

Estimate of the prevalence of subjects with chronic diseases in a province of Northern Italy: a retrospective study based on administrative databases.

OBJECTIVE: To find a definition of chronic disease based on literature review and to estimate the population-based prevalence rate of chronicity in a province in Northern Italy. DESIGN: Retrospective observational study based on administrative databases. DATA SOURCES/SETTING: Archives of the National Health Service that contain demographic and administrative information linked with the archives of ticket exemptions (2000-2019), the hospital discharge and drug prescriptions (2016-2019). PARTICIPANTS: Subjects who lived in Vercelli Local Health Authority, a Northern Italian province (Piedmont region), and were alive in December 2019. MAIN OUTCOME MEASURES: Prevalence of subjects with at least one chronic disease identified by administrative sources and stratification of population according to the number of comorbidities. The pathologies considered were: chronic ischaemic heart disease, congestive heart failure, cardiac arrhythmias, hypertension, stroke, neoplasm, asthma, chronic obstructive pulmonary disease, diabetes, thyroid disorders, osteoporosis, rheumatoid arthritis, chronic kidney disease, dementia, autism spectrum disorder, depression, schizophrenia, hepatitis, HIV and substance use disorders. RESULTS: Our target population was about 164 344 subjects. The overall prevalence of subjects with at least one chronic condition was 21.43% (n=35 212): 19 541 were female and 15 671 were male with a raw prevalence of 22.96% and 19.77%, respectively. The overall prevalence increases with age until 85 years old, then a decrease is observed. Moreover, 16.39% had only one pathology, 4.30% two diseases and 0.74% had a more complex clinical condition (more than three diseases). CONCLUSIONS: Despite the difficulty of having a unique definition of chronic disease, the prevalence obtained was coherent with the estimates reported by other national surveillance systems such as Passi and Passi d'Argento. Underestimates were observed when international comparisons were done; however, when we used less stringent definitions of chronic diseases, similar results were obtained.

Formaldehyde and Acetaldehyde Exposure in "Non-Traditional" Occupational Sectors: Bakeries and Pastry Producers.

INTRODUCTION: Formaldehyde, a colorless and highly irritating substance, causes cancer of the nasopharynx and leukemia. Furthermore, it is one of the environmental mutagens to which humans are most abundantly exposed. Acetaldehyde was recently classified as carcinogen class 1B and mutagen class 2 in Annex VI EC regulation. Occupational exposure to the two aldehydes occurs in a wide variety of occupations and industries. The aim of this study is to deepen exposure to the two aldehydes in the non-traditional productive sectors of bakeries and pastry producers. METHODS: The evaluation of exposure to formaldehyde and acetaldehyde was conducted in Italy in 2019, in specific tasks and positions of 11 bakeries and pastry producers (115 measures, of which 57.4% were in fixed positions and the rest were personal air sampling). The measurements were performed using Radiello© radial diffusion samplers. A logarithmic transformation of the data was performed, and the correlation between the two substances was calculated. Moreover, linear models considering the log-formaldehyde as the outcome and adjusting for log-acetaldehyde values were used. RESULTS: The study identified high levels of acetaldehyde and formaldehyde exposure in the monitored workplaces. Higher mean values were observed in the leavening phase (8.39 µg/m3 and 3.39 µg/m3 for log-transformed data acetaldehyde and formaldehyde, respectively). The adjusted univariate analyses show statistically significant factors for formaldehyde as the presence of yeast, the presence of type 1 flour, the use of barley, the use of fats, the type of production, the use of spelt, and the presence of type 0 flour. CONCLUSIONS: The measurements confirmed the release of formaldehyde and acetaldehyde in bakeries and pastry industries, especially in some phases of the work process, such as leavening.

In-Hospital Predictors of Need for Ventilatory Support and Mortality in Chest Trauma: A Multicenter Retrospective Study.

Chest trauma management often requires the use of invasive and non-invasive ventilation. To date, only a few studies investigated the predictors of the need for ventilatory support. Data on 1080 patients with chest trauma managed in two different centers were retrospectively analyzed. Univariate and multivariate analyses were performed to identify the predictors of tracheal intubation (TI), non-invasive mechanical ventilation (NIMV), and mortality. Rib fractures (p = 0.0001) fracture of the scapula, clavicle, or sternum (p = 0.045), hemothorax (p = 0.0035) pulmonary contusion (p = 0.0241), and a high Injury Severity Score (ISS) (p ≤ 0001) emerged as independent predictors of the need of TI. Rib fractures (p = 0.0009) hemothorax (p = 0.0027), pulmonary contusion (p = 0.0160) and a high ISS (p = 0.0001) were independent predictors of NIMV. The center of trauma care (p = 0.0279), age (p < 0.0001) peripheral oxygen saturation in the emergency department (p = 0.0010), ISS (p < 0.0001), and Revised Trauma Score (RTS) (p < 0.0001) were independent predictors of outcome. In conclusion, patients who do not require TI, while mandating ventilatory support with selected types of injuries and severity scores, are more likely to be subjected to NIMV. Trauma team expertise and the level of the trauma center could influence patient outcomes.

Use of fluorescein sodium-assisted intraoperative sample validation to maximize the diagnostic yield of stereotactic brain biopsy: progress toward a new standard of care?

OBJECTIVE: In patients with contraindication to open resection, histological diagnosis is obtained through a stereotactic biopsy (SB). Missed diagnoses and sampling errors are important limitations of SB; therefore, various ways have been proposed to increase the diagnostic yield (DY). Intraoperative histopathology can obtain a DY exceeding 98% but with several drawbacks, namely prolonged operative times and logistic concerns. The objective of this study was to evaluate whether intraoperative validation of samples with fluorescein sodium can obtain a high DY with the same ease of use as standard SB. METHODS: One hundred three consecutive cases of frameless neuronavigated SB performed at the authors' center from May 2013 to June 2021 were included. Two groups were compared: 46 patients underwent standard nonassisted SB (nSB), and 57 patients underwent fluorescein sodium-assisted SB (fSB). Data were collected retrospectively before 2017 and prospectively thereafter. DY, operative time, and rate of complications were compared between the two groups. The surgical technique for fSB was standardized, and a novel classification system for intraoperative fluorescence findings was developed. RESULTS: Statistically significant differences between the two groups were identified. The DY of the fSB group (100%, 95% CI 93.73%-100%) was significantly greater than that of the nSB group (89.13%, 95% CI 80.14%-98.13%) (p = 0.0157). No statistically significant differences were observed in terms of mean operative time (p = 0.7104), intraoperative complications (p = 0.999), or postoperative complications (p = 0.5083). CONCLUSIONS: Compared with standard nSB, fSB showed a significantly higher DY and similar surgical time and rate of complications. The ease of use, wide diagnostic spectrum, and low cost make fluorescein sodium preferable to other fluorophores. The present study strengthens the limited data in the literature indicating routine use of fSB. The proposed workflow suggests that fSB should be the standard of care for contrast-enhanced cases. Intraoperative histopathology should be limited to nonenhancing cases, and nSB should be avoided. Future prospective multicenter studies will be useful for further validation of our findings.

AKASI and Near-Infrared Spectroscopy in the combined effectiveness evaluation of an actinic keratoses preventive product in immunocompetent and immunocompromised patients.

Introduction: The high incidence of actinic keratoses among both the elderly population and immunocompromised subjects and the considerable risk of progression from in situ to invasive neoplasms makes it essential to identify new prevention, treatment, and monitoring strategies. Objective: The aim of this study was to evaluate the efficacy on AKs of a topical product (®Rilastil AK Repair 100 +) containing high-protection sunscreens, a DNA Repair Complex with antioxidant and repairing action against UV-induced DNA damage, and nicotinamide, a water-soluble derivative of vitamin B3 that demonstrated several photoprotective effects both in vitro and in vivo. Methods: The study enrolled 74 Caucasian patients, which included 42 immunocompetent and 32 immunosuppressed subjects. The efficacy of the treatment has been evaluated through the clinical index AKASI score and the non-invasive Near-Infrared Spectroscopy method. Results: The AKASI score proved to be a valid tool to verify the efficacy of the product under study, highlighting an average percentage reduction at the end of treatment of 31.37% in immunocompetent patients and 22.76% in organ transplant recipients, in comparison to the initial values, with a statistically significant reduction also in the single time intervals (T0 vs. T1 and T1 vs. T2) in both groups. On the contrary, the Near-Infrared Spectroscopy (a non-invasive technique that evaluates hemoglobin relative concentration variations) did not find significant differences for O2Hb and HHb signals before and after the treatment, probably because the active ingredients of the product under study can repair the photo-induced cell damage, but do not significantly modify the vascularization of the treated areas. Conclusion: The results deriving from this study demonstrate the efficacy of the product under study, confirming the usefulness of the AKASI score in monitoring treated patients. Near-Infrared Spectroscopy could represent an interesting strategy for AK patients monitoring, even if further large-scale studies will be needed.

Comparative efficacy of novel combination strategies for unresectable hepatocellular carcinoma: A network metanalysis of phase III trials.

BACKGROUND: Dual programmed cell death-1 and vascular endothelial growth factor pathway inhibition is the novel standard of care for patients with unresectable hepatocellular carcinoma. Direct comparisons between first-line treatments are lacking. METHOD: We conducted a literature search in MEDLINE (https://pubmed.ncbi.nlm.nih.gov), the Cochrane library (https://www.cochranelibrary.com) and Embase (www.embase.com) between January 2007 and February 2022. We included phase III randomised controlled trials that tested immune-checkpoint inhibitors or tyrosine kinase inhibitors, including sorafenib, lenvatinib and donafenib, and evaluated as primary end-point overall survival (OS) or progression-free survival (PFS). Studies testing loco-regional therapies were excluded. The primary end-point was to compare the efficacy of first-line options in terms of OS and PFS. We extracted Hazard ratios (HR) and 95% confidence intervals (95% CI) for OS and PFS and performed a frequentist network meta-analysis with fixed effect multivariable meta-regression models. The research protocol was registered in PROSPERO, an international prospective register of systematic reviews (registration code CRD42022312489). FINDINGS: Literature review yielded 13709 results, after duplicates removal and exclusion of not relevant studies, 70 papers were available for screening. After full-text review, 9 studies were eligible for analysis. Atezolizumab plus bevacizumab reduced the risk of death compared to placebo (HR 0·40; 95% CI 0·28-0·57), sorafenib (HR 0·58; 95% CI 0·42-0·80), lenvatinib (HR 0·63; 95% CI 0·44-0·89), atezolizumab plus cabozantinib (HR 0·64; 95% CI 0·43-0·97), nivolumab (HR 0·68; 95% CI 0·48-0·98) and donafenib (HR 0·69; 95% CI 0·48-0·99). Atezolizumab plus bevacizumab was not statistically superior to durvalumab plus tremelimumab (HR 0·74; 95% CI 0·52-1·06) and sintilimab plus IBI305 (HR 1·02; 95% CI 0·67-1·55) in reducing the risk of death. Efficacy was associated with a higher risk of grade 3 adverse events.

Non-timely clinically applicable ADC ratio in prostate mpMRI: a comparison with fusion biopsy results.

PURPOSE: The purpose of the study was to assess the diagnostic accuracy of ADC ratio and to evaluate its efficacy in reducing the number of false positives in prostatic mpMRI. MATERIALS AND METHODS: All patients who underwent an mpMRI and a targeted fusion biopsy in our institution from 2016 to 2021 were retrospectively selected. Two experienced readers (R1 and R2) independently evaluated the images, blindly to biopsy results. The radiologists assessed the ADC ratios by tracing a circular 10 mm2 ROI on the biopsied lesion and on the apparently benign contralateral parenchyma. Prostate cancers were divided into non-clinically significant (nsPC, Gleason score = 6) and clinically significant (sPC, Gleason score ≥ 7). ROC analyses were performed. RESULTS: 167 patients and188 lesions were included. Concordance was 0.62 according to Cohen's K. ADC ratio showed an AUC for PCAs of 0.78 in R1 and 0.8 in R2. The AUC for sPC was 0.85 in R1 and 0.84 in R2. The 100% sensitivity cut-off for sPCs was 0.65 (specificity 25.6%) in R1 and 0.66 (specificity 27.4%) in R2. Forty-three benign or not clinically significant lesions were above the 0.65 threshold in R1; 46 were above the 0.66 cut-off in R2. This would have allowed to avoid an equal number of unnecessary biopsies at the cost of 2 nsPCs in R1 and one nsPC in R2. CONCLUSION: In our sample, the ADC ratio was a useful and accurate tool that could potentially reduce the number of false positives in mpMRI.

Teledermoscopy in the Diagnosis of Melanocytic and Non-Melanocytic Skin Lesions: NurugoTM Derma Smartphone Microscope as a Possible New Tool in Daily Clinical Practice.

Background: Due to the COVID-19 pandemic, teledermoscopy has been increasingly used in the remote diagnosis of skin cancers. In a study conducted in 2020, we demonstrated a potential role of an inexpensive device (NurugoTM Derma) as a first triage to select the skin lesions that require a face-to-face consultation with dermatologists. Herein, we report the results of a novel study that aimed to better investigate the performance of NurugoTM. Objectives: (i) verify whether the NurugoTM can be a communication tool between the general practitioner (GP) and dermatologist in the first assessment of skin lesions, (ii) analyze the degree of diagnostic-therapeutic agreement between dermatologists, (iii) estimate the number of potentially serious diagnostic errors. Methods: One hundred and forty-four images of skin lesions were collected at the Dermatology Outpatient Clinic in Novara using a conventional dermatoscope (instrument F), the NurugoTM (instrument N), and the latter with the interposition of a laboratory slide (instrument V). The images were evaluated in-blind by four dermatologists, and each was asked to make a diagnosis and to specify a possible treatment. Results: Our data show that F gave higher agreement values for all dermatologists, concerning the real clinical diagnosis. Nevertheless, a medium/moderate agreement value was obtained also for N and V instruments and that can be considered encouraging and indicate that all examined tools can potentially be used for the first screening of skin lesions. The total amount of misclassified lesions was limited (especially with the V tool), with up to nine malignant lesions wrongly classified as benign. Conclusions: NurugoTM, with adequate training, can be used to build a specific support network between GP and dermatologist or between dermatologists. Furthermore, its use could be extended to the diagnosis and follow-up of other skin diseases, especially for frail patients in emergencies, such as the current pandemic context.

Are Baseline Levels of Gas6 and Soluble Mer Predictors of Mortality and Organ Damage in Patients with Sepsis? The Need-Speed Trial Database.

Soluble tyrosine kinase receptor Mer (sMer) and its ligand Growth arrest-specific protein 6 (Gas6) are predictors of mortality in patients with sepsis. Our aim is to clarify whether their measurement at emergency department (ED) presentation is useful in risk stratification. We re-analyzed data from the Need-Speed trial, evaluating mortality and the presence of organ damage according to baseline levels of sMer and Gas6. 890 patients were eligible; no association with 7- and 30-day mortality was observed for both biomarkers (p > 0.05). sMer and Gas6 levels were significantly higher in acute kidney injury (AKI) patients compared to non-AKI ones (9.8 [4.1-17.8] vs. 7.9 [3.8-12.9] ng/mL and 34.8 [26.4-47.5] vs. 29.8 [22.1-41.6] ng/mL, respectively, for sMer and Gas6), and Gas6 also emerged as an independent AKI predictor (odds ratio (OR) 1.01 [1.00-1.02]). Both sMer and Gas6 independently predicted thrombocytopenia in sepsis patients not treated with anticoagulants (OR 1.01 [1.00-1.02] and 1.04 [1.02-1.06], respectively). Moreover, sMer was an independent predictor of both prothrombin time-international normalized ratio (PT-INR) > 1.4 (OR 1.03 [1.00-1.05]) and sepsis-induced coagulopathy (SIC) (OR 1.05 [1.02-1.07]). An early measurement of the sMer and Gas6 plasma concentration could not predict mortality. However, the biomarkers were associated with AKI, thrombocytopenia, PT-INR derangement and SIC, suggesting a role in predicting sepsis-related organ damage.

Effectiveness and feasibility of smoking counselling: a randomized controlled trial in an Italian emergency department.

BACKGROUND: 5A's counselling is recommended for screening and treating patients with smoking addiction. The emergency department (ED) setting might be a suitable environment for conducting interventions for smoking cessation. The present study aims to determine the feasibility and effectiveness on smoking cessation of 5A's counselling administered to ED patients by nurses. METHODS: Parallel group randomized trial assessing 5A's counselling for smoking cessation vs. usual care at a University Hospital in the North of Italy. The primary end-point was prevalence of tobacco-free patients. The secondary outcomes at 6- and 12-month follow-up were (i) consecutive past 30-day smoking abstinence; (ii) past 7-day 50%, or more, decrease in daily tobacco consumption over baseline; and (iii) number of attempts to quit smoking. RESULTS: A total of 480 patients were randomized to intervention (n = 262) or usual care (n = 218). Intention to treat analysis displayed no differences in primary and secondary outcomes between groups. A slight but not statistically significant enhancement in cessation was recorded in the intervention group [relative risk (RR) = 1.04, 95% confidence interval (CI) = 0.58-1.87] at 6 months, whereas a reversed observation at 12 months (RR = 0.86, 95% CI = 0.50-1.47). Similar results were obtained for the secondary outcomes. Per protocol analysis increased the size of the results. Of the 126 smokers receiving counselling, 18 were visited and treated at the local smoking cessation centre, with 12 of them successfully completing the treatment. CONCLUSION: The results of this study indicate that the ED is not a suited environment for 5A's counselling.

Use of State Sequence Analysis in Pharmacoepidemiology: A Tutorial.

While state sequence analysis (SSA) has been long used in social sciences, its use in pharmacoepidemiology is still in its infancy. Indeed, this technique is relatively easy to use, and its intrinsic visual nature may help investigators to untangle the latent information within prescription data, facilitating the individuation of specific patterns and possible inappropriate use of medications. In this paper, we provide an educational primer of the most important learning concepts and methods of SSA, including measurement of dissimilarities between sequences, the application of clustering methods to identify sequence patterns, the use of complexity measures for sequence patterns, the graphical visualization of sequences, and the use of SSA in predictive models. As a worked example, we present an application of SSA to opioid prescription patterns in patients with non-cancer pain, using real-world data from Italy. We show how SSA allows the identification of patterns in prescriptions in these data that might not be evident using standard statistical approaches and how these patterns are associated with future discontinuation of opioid therapy.

Is there a preferred first-line therapy for metastatic renal cell carcinoma? A network meta-analysis.

BACKGROUND: In recent years, new therapeutic combinations based on immunotherapy provided significant benefits as a first-line treatment for patients with advanced renal cell carcinoma (mRCC). OBJECTIVE: This work aims to address the lack of head-to-head comparisons and the uncertainty of the benefit from immunotherapy-based combinations in all the International Metastatic RCC Database Consortium (IMDC) subgroups. DESIGN SETTING AND PARTICIPANTS: A systematic review and a network meta-analysis were performed. Overall survival (OS) in the intention-to-treat (ITT) population was the primary endpoint. OS according to IMDC subgroups (favorable, intermediate, poor), PD-L1 expression, and grade ⩾3 adverse events (AEs) were secondary endpoints. A SUCRA analysis was performed. RESULTS AND LIMITATIONS: Six randomized phase III trials with 5121 patients were included. There was a high likelihood (82%) that nivolumab-cabozantinib was the preferred treatment in OS. The benefit of ICI-based combinations over sunitinib was unclear in the favorable-risk subgroup. Nivolumab-ipilimumab had the best risk/benefit ratio among all the ICI-based combinations. The limitations were the lack of individual patient data; the heterogeneity of patients' characteristics, trial designs, and follow-up times; and a limited number of studies for indirect comparisons. CONCLUSIONS: A customized approach for the first-line treatment of patients with mRCC should consider the risk/benefit profile of each treatment option, especially considering the likeliness of long-term survival finally reached in this setting.

4D Electromagnetic Navigation Bronchoscopy for the Sampling of Pulmonary Lesions: First European Real-Life Experience.

PURPOSE: The use of Electromagnetic navigation bronchoscopy (ENB) for the diagnosis of pulmonary peripheral lesions is still debated due to its variable diagnostic yield; a new 4D ENB system, acquiring inspiratory and expiratory computed tomography (CT) scans, overcomes respiratory motion and uses tracked sampling instruments, reaching higher diagnostic yields. We aimed at evaluating diagnostic yield and accuracy of a 4D ENB system in sampling pulmonary lesions and at describing their influencing factors. METHODS: We conducted a three-year retrospective observational study including all patients with pulmonary lesions who underwent 4D ENB with diagnostic purposes; all the factors potentially influencing diagnosis were recorded. RESULTS: 103 ENB procedures were included; diagnostic yield and accuracy were, respectively, 55.3% and 66.3%. We reported a navigation success rate of 80.6% and a diagnosis with ENB was achieved in 68.3% of cases; sensitivity for malignancy was 61.8%. The majority of lesions had a bronchus sign on CT, but only the size of lesions influenced ENB diagnosis (p < 0.05). Transbronchial needle aspiration biopsy was the most used tool (93.2% of times) with the higher diagnostic rate (70.2%). We reported only one case of pneumothorax. CONCLUSION: The diagnostic performance of a 4D ENB system is lower than other previous navigation systems used in research settings. Several factors still influence the reachability of the lesion and therefore diagnostic yield. Patient selection, as well as the multimodality approach of the lesion, is strongly recommended to obtain higher diagnostic yield and accuracy, with a low rate of complications.