Safety, Effectiveness and Pitfalls of Carbon Dioxide Routine Use as a Contrast Agent for Endovascular Abdominal Aortic Repair.

BACKGROUND: Despite the evidence of good performance, carbon dioxide (CO2) routine employment as a contrast agent for endovascular procedures is far from being adopted with its use currently limited to patients with renal impairment and known allergy to iodinated contrast medium (ICM). The purpose of our study is to evaluate the safety and effectiveness of CO2 guided endovascular abdominal aortic aneurysm repair (EVAR) in a standard population and to assess the rationale for a future widespread use. METHODS: We retrospectively collected data of every patient who underwent CO2 guided standard EVAR from September 2020 to May 2021 and compared them with the data of every patient who underwent EVAR using ICM from December 2019 to August 2020 in our unit. The selection of the contrast medium was not based on any preoperative factor as the contrast medium was routinely used in every patient in both periods. The primary end point of the study was the technical success rate. Secondary end points were the early and late complication rates, radiation exposure and renal function impairment. RESULTS: 49 patients underwent ICM guided EVAR and 52 patients underwent CO2 guided EVAR in our unit in the time frames specified above. The technical success rate was 100% in both groups with no accidental coverage of any target vessel. Intraoperative endoleaks were observed in 14% of ICM patients and 25% of CO2 patients. The radiation exposure was higher in the CO2 group if compared to the ICM group (311.48 vs. 159.86 median mGy/cm2 - P < 0.001). The incidence of postoperative acute kidney injury was low and similar in the 2 groups. No significant worsening over time of the renal function has been reported in both groups. CONCLUSIONS: EVAR can be safely performed under CO2 guidance without the integration of any quantity of ICM but with an increase in radiation exposure. The nephroprotective role of CO2 guided EVAR in a standard population is unclear and the same role in renal impaired patients should be validated with further studies on selected populations.

Missed nursing care and stoma care: an Italian survey.

BACKGROUND: In Italy, nursing research has paid special attention to 'missed nursing care'. The studies carried out, varying in tools and settings, describe considerable percentages of missed care. In the field of stoma care, the phenomenon has not been investigated to date. AIM: To investigate the prevalence of missed nursing care (MNC) in the Italian ostomy patient population and the most relevant causes suggested for this by stoma care nurses. DESIGN: Cross-sectional study. METHOD: The Italian version of the MISSCARE survey was used with some questions related to the stoma care pathway. The survey was targeted at hospitals in the country with dedicated services and/or pathways for ostomy patients, between February and April 2023. FINDINGS: A total of 461 questionnaires were sent out, 214 (53.3%) were analysed. The majority of the participants were female (160, 76.2%), median age of 50 years (35.0-53.8). The most common qualification was a Bachelor's degree (n=117; 54.9%) and work experience in stoma care was more than 10 years in 95 cases (50.3%). Prominent instances of MNC were identified, with hand washing (score 4.6 out of 5), compilation of nursing documentation and hygiene/skin care (score 4.5 out of 5) and patient/family education (score 4.4 out of 5) emerging as the most prevalent. The most notable omissions in the stoma care process encompassed educational facets, clinical monitoring, a comprehensive discharge plan, and diligent follow-up. Among the most frequent reasons were staff shortages (score 3.1 out of 4), unsuitable nurse-patient ratios (score of 3 out of 4) and insufficient numbers of experienced stoma care personnel (score of 3 out of 4). CONCLUSION: A substantial number of basic and clinically relevant nursing interventions were perceived to be missed, and this may lead to an increase in negative outcomes for ostomy patients.

MRI-detected extramural vascular invasion (mrEMVI) as the best predictive factor to identify candidates to total neoadjuvant therapy in locally advanced rectal cancer.

BACKGROUND AND OBJECTIVES: Chemotherapy in locally advanced rectal cancer (LARC) is shifting from an adjuvant setting to a total neoadjuvant therapy (TNT) strategy, that relies on distant metastases (DM) risk prediction. This study aims to assess the accuracy of magnetic resonance imaging-detected extramural vascular invasion (mrEMVI) as predictive factor for DM in LARC, compared with other MRI-detected and pathologic factors. METHODS: This retrospective single-center study analyzed data extracted from a series of consecutive patients curatively resected for rectal cancer at Mauriziano Hospital in Turin (Italy) from January 2013 to December 2018. RESULTS: Data from 69 patients were analyzed. MrEMVI was detected in 31 (44.9%) cases. Median follow-up was 39.9 months. DM and local recurrence occurred in 19 (27.5%) and 4 (5.8%) patients. One- and 3-year cumulative incidence of DM were 32.3% (95% confidence interval [CI]: 0.17-0.49) and 56.8% (95% CI: 0.35-0.74) in the mrEMVI-positive group and 5.4% (95% CI: 0.01-0.16) and 14.0% (95% CI: 0.05-0.27) in the mrEMVI-negative group (log-rank test, p < 0.001). In the multivariate analysis of MRI factors, mrEMVI was the only independent predictor of DM (HR: 3.59, CI: 1.21-10.69, p = 0.02). CONCLUSIONS: This study confirmed that mrEMVI is a powerful predictor of DM in LARC. It should be routinely reported and considered during multidisciplinary care strategy planning.

A close adherence to a stoma-therapeutic pathway improves immediate stoma-related outcomes and reduces the length of hospital stay.

PURPOSE: New stoma creation is related to a wide range of implications and stoma-related complications could occur frequently. The aim was to assess the impact of a close stoma-therapeutic-care pathway (STCP) in terms of length of stay, autonomy in the management of the pouch, readmission rate, and stoma-related complications. METHODS: Patients undergoing surgery for colorectal disease and first stoma creation from January 2017 to December 2020 were analyzed. All patients enrolled had joined the Enhanced Recovery after Surgery (ERAS) protocol. RESULTS: Among 143 enrolled, 56 (40%) did not completely follow the STCP (group A), whereas 87 (60%) demonstrated strict compliance (group B). The hospital stay lasted 8 days in group B and 11.5 in group A (p = 0.001). The first look at the stoma needed 1 day in group B and 3 days in group A (p < 0.001), emptying the pouch 2 days in group B and 5 days in group A (p < 0.001). Finally, the ability to change the pouch was 3 days in group B and 6 days in group A (p < 0.001). Nine (16.1%) stoma-related complications were counted in group A and 16 (18.4%) in group B, and 30-day readmission was 10.1% in group B and 11.5% in group A (p = 0.82 and p = 1, respectively, not significant). CONCLUSIONS: The STCP has been shown to reduce the hospital stay and to have a protective role making the patient autonomous in the management of the stoma.

Long-term failure after endovascular aneurysm sealing in a real-life, single-center experience with the Nellix endograft.

BACKGROUND: Endovascular aneurysm sealing (EVAS) is an innovative alternative to conventional endovascular aneurysm repair (EVAR). EVAS relies on sac anchoring without proximal fixation to achieve sealing and should have allowed for the treatment of a broader range of anatomic features compared with standard EVAR. Despite the encouraging early reports, the mid- and long-term follow-up data have shown increased rates of failure. To address the issue, the manufacturer introduced revised instructions for use (IFU) in 2016. The present study reports the outcomes of this system after a median follow-up of 45 months. METHODS: Data for all patients electively treated with EVAS at our institution were retrospectively collected. The patients were retrospectively reclassified according to the 2016 revised IFU of the device. All patients in the present series had undergone EVAS for the treatment of infrarenal abdominal aortic aneurysms (AAAs). The primary end point was therapeutic failure: graft migration >5 mm, sac expansion >5 mm, type IA endoleak (Is2 and Is3 using the Van den Ham classification), type Ib endoleak, and secondary rupture. The overall mortality, aortic-related mortality, and reintervention rates were also analyzed. RESULTS: A total of 101 patients had undergone elective treatment by EVAS from 2013 to 2018 for infrarenal AAAs. The median follow-up was 3.75 years. Therapeutic failure was observed in 31 of the 101 patients (30.7%), with no significant difference between the in-IFU and off-IFU 2016 subgroups. Failure occurred at a median interval of 34 months from the index procedure. Of the 101 patients, 6.9% had presented with secondary rupture. Freedom from aneurysm-related mortality was 96.9% at 1 and 2 years and 89.9% at 5 years. Freedom from reintervention decreased over time: 94.7% at 1 year, 77% at 4 years, and 52.1% at 6 years. Of the 101 patients, 14 (13.9%) had undergone emergent or elective graft explantation. CONCLUSIONS: EVAS performed worse than conventional endografts for several critical end points, regardless of any preoperative anatomic parameters. The incidence of therapeutic failures tended to increase over time, especially 4 years after the index procedure.

CARotid plaqUe StabilizatiOn and regression with evolocumab: Rationale and design of the CARUSO study.

BACKGROUND: While the experience with PCSK9i in patients with coronary artery disease has been wide, and coronary plaque regression has been documented, little is known regarding the role of these drugs on carotid plaque regression. The CARotid plaqUe StabilizatiOn and regression with evolocumab (CARUSO) study is a randomized, single-center, investigator-initiated trial aiming at evaluating carotid plaque morphological stabilization and regression following, respectively, 6 and 12 months of therapy with evolocumab. METHODS: Asymptomatic patients with uni- or bilateral de novo carotid artery stenosis ≥50% and LDL-C values ≥100 mg/dl despite maximum tolerated lipid lowering therapy (LLT) will be randomized to evolocumab 140 mg s.c. every 2 weeks on top of ongoing LLT, or no additional treatment. 100 patients (50 in each arm) will be enrolled. Serial carotid duplex ultra-sonography will be performed to monitor the carotid plaque morphology and stenosis over time. RESULTS: The primary end point of the study is, (a) carotid plaque morphological stabilization at 6 months, defined as defined as the disappearance of ulcerations and fluffy components and the achievement of a regular plaque morphology with prevalence of fibrous atheroma and/or (b) carotid plaque regression at 12 months, defined as reduction of the entity of the stenosis and/or peak systolic velocity by at least 5%, as compared with baseline. CONCLUSION: The CARUSO trial will test the superiority of evolocumab on top of ongoing LLT versus ongoing LLT alone regarding carotid plaque morphological stabilization and regression. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Workplace well-being of Advanced Practice Nurses and patient outcomes.

BACKGROUND: Workplace well-being has been defined as a state of pleasure in doing your own job. Work engagement is an effective indicator to measure workplace well-being. AIM: To investigate the level of work engagement among the Advanced Practice Nurses and describe patient outcomes. METHODS: A survey based on Utrecht Work Engagement Scale-17 (ranging 0-6) was administered to 11 Advanced Practice Nurses; data were collected in August 2021. Different outcomes were detected: incidence of pressure ulcers in COVID 19 patients; postoperative issues; number of cornea donations in eligible patients (from 2017 to 2020); number of preoperative stoma site marking. RESULTS: The results showed a median age of 48 [41-52] years, most of the partecipants were women (63.64%). Advanced Practice Nurses showed high levels of engagement as a whole (5.18 0.30) and on vigor (4.91 0.82), dedication (5.51 0.80) and absorption categories (5.12 0.68). 360 patients with COVID-19 were observed and only 17 of them (4,5%) had Pressure Ulcers (density incidence: 2,72ulcers/1000 patients day). Intervention by case manager completely solved the patient's problem in 10 cases (71.43%) during the postoperative period. A 13% increase in corneal donations was observed in eligible patients from 2017 to 2020. Preoperative stoma site marking was present in 103 (99.3%) of eligible patients. CONCLUSIONS: Advanced Practice Nurses present high levels of work engagement. Outcome results are coherent with the literature; a high level of work engagement seems to correlate with better patient outcomes. NURSING IMPLICATIONS: Postgraduate nursing training improves clinical outcomes for patients and process indicators. Healthcare organizations management should value workplace well-being of their Advanced Practice Nurses.

Mechanism of Action of Inhaled Insulin on Whole Body Glucose Metabolism in Subjects with Type 2 Diabetes Mellitus.

In the current study we investigate the mechanisms of action of short acting inhaled insulin Exubera®, on hepatic glucose production (HGP), plasma glucose and free fatty acid (FFA) concentrations. 11 T2D (Type 2 Diabetes) subjects (age = 53 ± 3 years) were studied at baseline (BAS) and after 16-weeks of Exubera® treatment. At BAS and after 16-weeks subjects received: measurement of HGP (3-3H-glucose); oral glucose tolerance test (OGTT); and a 24-h plasma glucose (24-h PG) profile. At end of study (EOS) we observed a significant decrease in fasting plasma glucose (FPG, 215 ± 15 to 137 ± 11 mg/dl), 2-hour plasma glucose (2-h PG, 309 ± 9 to 264 ± 11 mg/dl), glycated hemoglobin (HbA1c, 10.3 ± 0.5% to 7.5 ± 0.3%,), mean 24-h PG profile (212 ± 17 to 141 ± 8 mg/dl), FFA fasting (665 ± 106 to 479 ± 61 µM), post-OGTT (433 ± 83 to 239 ± 28 µM), and triglyceride (213 ± 39 to 120 ± 14 mg/dl), while high density cholesterol (HDL-C) increased (35 ± 3 to 47 ± 9 mg/dl). The basal HGP decreased significantly and the insulin secretion/insulin resistance (disposition) index increased significantly. There were no episodes of hypoglycemia and no change in pulmonary function at EOS. After 16-weeks of inhaled insulin Exubera® we observed a marked improvement in glycemic control by decreasing HGP and 24-h PG profile, and decreased FFA and triglyceride concentrations.

Real-life efficacy and safety of cemiplimab in advanced cervical cancer from a nominal use program in Italy: The MITO 44 study.

BACKGROUND: cemiplimab is an immunoglobulin G4 monoclonal antibody targeting the programmed cell death-1 receptor. A nominal use program is available in Italy in advanced cervical cancer (CC) patients treated with platinum based chemotherapy based on the results of EMPOWER-Cervical 1/GOG-3016/ENGOTcx9 trial. This real-world, retrospective cohort, multicenter study aimed at describing clinical outcomes of patients with advanced CC treated with cemiplimab in Italy. METHODS: The primary objective of the study was to assess the feasibility and the replicability of the initial results in a real world setting of cemiplimab nominal use. The primary endpoint of our analysis was progression free survival (PFS). Secondary endpoints included overall response rate (ORR), overall survival (OS) and safety data. RESULTS: From March 2022 to December 2023, 135 patients were treated in 12 Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) Centers. Forty-two percent of patients had one or more comorbidities, hypertension being the most common (23.4%). Median PFS was 4.0 months (range 3.0-6.0) and median OS was 12.0 months (12.0- NR) with no differences according to PD-L1 status. Complete response (CR) or no evidence of disease (NED) were observed in 8.6%; partial response (PR) in 21.1%, stable disease (SD) in 14.8% and progression was recorded in 44.5% of patients. Most common drug related adverse events (AEs) were anemia (39.1%) and fatigue (27.8%). Immune related AEs occurred in 18.0%. CONCLUSIONS: This study confirms the feasibility and the replicability of the cemiplimab nominal use in advanced CC, in a real-world practice in Italy.

Transcatheter Ablation of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy: A Multicenter Propensity Score-Based Analysis.

Background: The prognostic impact of catheter ablation (CA) of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients has not yet been satisfactorily elucidated. Objectives: The aim of the study was to assess the impact of CA of AF on clinical outcomes in a large cohort of HCM patients. Methods: In this retrospective multicenter study, 555 HCM patients with AF were enrolled, 140 undergoing CA and 415 receiving medical therapy. 1:1 propensity score matching led to the inclusion of 226 patients (113 medical group, 113 intervention group) in the final analysis. The primary outcome was a composite of all-cause mortality, heart transplant and acute heart failure exacerbations. Secondary outcomes included AF recurrence and transition to permanent AF. Additionally, an inverse probability weighted (IPW) model was examined. Results: At propensity score matching analysis, after a median follow-up of 58.1 months, the primary endpoint occurred in 29 (25.7%) patients in intervention group vs 42 (37.2%) in medical group (P = 0.9). Thromboembolic strokes and major arrhythmic events in intervention vs medical group were 9.7% vs 7.1% (P = 0.144) and 4.4 vs 8.0% (P = 0.779), respectively. Fewer patients in intervention vs medical group experienced AF recurrences (63.7% vs 84.1%, P = 0.001) and transition to permanent AF pattern (20.4% vs 33.6%, P = 0.026). IPW analysis showed consistent results. Severe complications related to CA were uncommon (0.7%). Conclusions: After 5 years of follow-up, CA did not improve major adverse cardiac outcomes in a large cohort of patients with HCM and AF. Nevertheless, CA seems to facilitate the maintenance of sinus rhythm and slow the progression to permanent AF, without significant safety concerns.

Inverse probability of treatment weighting analysis of laparoscopic versus open Sg4b-5 bi-segmentectomy in patients with gallbladder cancer.

Sg4b-5 anatomical bi-segmentectomy with regional lymphadenectomy (Sg4b5) is a surgical option for gallbladder cancer (GBC) treatment. The laparoscopic approach to this challenging operation is still controversial. Aim of this study was to compare short- and long-term outcomes of laparoscopic versus open Sg4b5 in a single institution series of patients. All consecutive patients who underwent Sg4b5 for GBC from January 2000 to September 2021 were retrospectively reviewed. Inverse probability of treatment weighting (IPTW) analysis was performed. 75 patients were analyzed, 18 in the laparoscopic and 57 in the open group. After IPTW, laparoscopic approach was associated with a significantly decreased median intraoperative blood loss (100 vs 237.09 ml, p = 0.001), shorter median length of hospital stay (4 vs 8 days, p = < 0.001) and a higher median number of harvested nodes (9 vs 7, p = 0.026). Operation time was shorter in the open group (355 vs 259 min, p < 0.001). No significant differences were found regarding clear resection margins, overall and major (Clavien-Dindo ≥ 3) morbidity, bile leakage rate, 90 days post-operative mortality, overall and disease-free survival. Laparoscopic Sg4b-5 anatomical bi-segmentectomy and regional lymphadenectomy is feasible and safe with long term outcome comparable to open approach at least in early stages. Laparoscopic approach confirms its well-known short-term benefits with less intraoperative bleeding and shorter length of stay. Moreover, it might allow a better lymphadenectomy.

MITO39: Efficacy and Tolerability of Pegylated Liposomal Doxorubicin (PLD)-Trabectedin in the Treatment of Relapsed Ovarian Cancer after Maintenance Therapy with PARP Inhibitors-A Multicenter Italian Trial in Ovarian Cancer Observational Case-Control Study.

OBJECTIVE: While PLD-Trabectedin is an approved treatment for relapsed platinum-sensitive ovarian cancer, its efficacy and tolerability has so far not been tested extensively in patients who progress after poly ADP-ribose polymerase inhibitor (PARPi) treatment. METHODOLOGY: This multicenter, retrospective analysis had the objective of comparing patients receiving PLD-Trabectedin after being treated with PARP-I (cases) with PARPi-naïve patients. Descriptive and survival analyses were performed for each group. RESULTS: Data from 166 patients were collected, composed of 109 cases and 57 controls. In total, 135 patients were included in our analyses, composing 46 controls and 89 cases. The median PFS was 11 months (95% IC 10-12) in the control group vs. 8 months (95% IC 6-9) in the case group (p value 0.0017). The clinical benefit rate was evaluated, with an HR for progression of 2.55 (1.28-5.06) for the case group (p value 0.008), persisting when adjusted for BRCA and line with treatment. We compared hematological toxicity, gastro-intestinal toxicity, hand-foot syndrome (HFS), fatigue, and liver toxicity, and no statistically significant disparity was noted, except for HFS with a p value of 0.006. The distribution of G3 and G4 toxicities was also equally represented. CONCLUSION: The MITO39 study showed a statistically significant difference in terms of PFS, suggesting that previous exposure to PARPi might inhibit the efficacy of PLD-Trabectedin. Regarding tolerability, no remarkable disparity was noted; PLD-Trabectedin was confirmed to be a well-tolerated scheme in both groups. To our knowledge, these are the first data regarding this topic, which we deem to be of great relevance in the current landscape.

Challenges in providing special care dentistry during COVID-19 pandemic: a survey of public dental care services in Italy.

BACKGROUND: The aim of this paper was to assess COVID-19 pandemic impact over the public health care services (HCS) involved in special care dentistry (SCD). METHODS: Customized questionnaire was sent to 45 HCS involved in SCD. Healthcare personnel (HP) on duty, safety of HCS, time of suspension and reduction of routine dental practice in special needs patients (SNP), kind of SNP mostly penalized during pre-COVID period/T1, lockdown (phase 1/T2) and post pandemic reopening (phase 2/T3) were analyzed by statistical means (P<0.05). RESULTS: 21 questionnaires were returned. A significant decrease of median number of HP during T2 was observed. Prevalence of COVID-19 infection among HP was not significantly different between T2 vs. T3. Medical surveillance of HP during T2 was significantly lower than during T3. Patients with lack of cooperation were the most disadvantaged during both phases dental procedures were significantly lower between T1 and T2 and between T1 and T3 as well. Patients with lack of cooperation and/or living in residential care homes were the most disadvantaged in relation to access to dental care during both phases. CONCLUSIONS: COVID-19 pandemic determined significant restrictions in daily access to routine oral care resulting in reduction of preventive evaluations and decline of oral health in a population which is already at a higher risk of oral pathologies. Our data reveal that reduction of dental procedures, healthcare professionals and days of suspension of clinical activity were still considerable also in T3 with respect to T1 and in some cases not significantly different from T2.

Suicide spectrum among young people during the COVID-19 pandemic: A systematic review and meta-analysis.

Background: There are concerns that suicidal behaviors are arising among adolescents. The COVID-19 pandemic could have worsened the picture, however, studies on this topic reported contrasting results. This work aimed to summarise findings from the worldwide emerging literature on the rates of suicidality among young people during the COVID-19 pandemic. Methods: A systematic review and meta-analysis were performed, searching five electronic databases for studies published from January 1, 2020 until July 27, 2022. Studies reporting rates for each of the three considered outcomes (suicide, suicidal behaviors, and suicidal ideation) among young people under 19 years old during the COVID-19 pandemic were included. Random-effects meta-analyses were conducted, and the intra-study risk of bias was assessed. When pre-COVID-19 data were available, incidence rate ratio (IRR) and prevalence ratio (PR) estimates were calculated between the two periods. All the analyses were performed according to the setting explored: general population, emergency department (ED), and psychiatric services. The review protocol was registered on PROSPERO (CRD42022308014). Findings: Forty-seven observational studies were selected for more than 65 million subjects. The results of the meta-analysis showed a pooled annual incidence rate of suicides of 4.9 cases/100,000 during 2020, accounting for a non-statistically significant increase of 10% compared to 2019 (IRR 1.10, 95% CI: 0.94-1.29). The suicidal behaviors pooled prevalence during the COVID-19 pandemic was higher in the psychiatric setting (25%; 95% CI: 17-36%) than in the general population (3%; 1-13%) and ED (1%; 0-9%). The pooled rate of suicidal ideation was 17% in the general population (11-25%), 36% in psychiatric setting (20-56%) and 2% in ED (0-12%). The heterogeneity level was over 97% for both outcomes in all settings considered. The comparison between before and during COVID-19 periods highlighted a non-statistically significant upward trend in suicidal behaviors among the general population and in ED setting. The only significant increase was found for suicidal ideation in psychiatric setting among studies conducted in 2021 (PR 1.15; 95% CI: 1.04-1.27), not observed exploring 2020 alone. Interpretation: During the pandemic, suicide spectrum issues seemed to follow the known pattern described in previous studies, with higher rates of suicidal ideation than of suicidal behaviors and suicide events. Governments and other stakeholders should be mindful that youth may have unique risks at the outset of large disasters like the COVID-19 pandemic and proactive steps are necessary to address the needs of youth to mitigate those risks. Funding: The present study was funded by the University of Torino (CHAL_RILO_21_01).

Incidence and Prevalence Analysis of Non-Small-Cell and Small-Cell Lung Cancer Using Administrative Data.

Treatment of lung cancer depends on the stage of the tumor and the histological type. In recent years, the histological confirmation of lung non-small-cell lung cancer has become crucial since the availability of selective target therapeutic approaches. The aim of the study was to develop a validated procedure to estimate the incidence and prevalence of non-small-cell and small-cell lung cancer from healthcare administrative data. A latent class model for categorical variables was applied. The following observed variables were included in the analysis: ICD-9-CM codes in the Hospital Discharge Registry, ATC codes of medications dispensed present in the Drugs Prescriptions Registry, and the procedure codes in the Outpatient Registry. The proportion of non-small-cell lung cancer diagnoses was estimated to be 85% of the total number of lung cancer on the cohort of incident cases and 89% on the cohort of prevalent cases. External validation on a cohort of 107 patients with a lung cancer diagnosis and histological confirmation showed a sensitivity of 95.6% (95%CI: 89-98.8%) and specificity of 94.1% (95%CI: 71.3-99.9%). The procedure is an easy-to-use tool to design subpopulation-based studies on lung cancer and to better plan resource allocation, which is important since the introduction of new targeted therapies in non-small-cell lung carcinoma.

Radioembolization vs sorafenib in locally advanced hepatocellular carcinoma with portal vein tumor thrombosis: A propensity score and Bayesian analysis.

OBJECTIVE: In this study we aimed to compare patient outcomes between the use of transarterial radioembolization (TARE) and sorafenib in patients with hepatocellular carcinoma (HCC) and intrahepatic portal vein tumor thrombosis (PVTT). METHODS: A total of 65 patients with HCC and intrahepatic PVTT treated in five Italian hospitals between 2012 and 2018 were included in the analysis. Those with any previous treatment, extension of PVTT to the main portal tract and extrahepatic involvement were excluded. Propensity score matching analysis and Bayesian model averaging analysis were performed. RESULTS: Of the 41 patients treated with TARE and 24 with sorafenib, 11 patients were downstaged to curative-intent surgery (liver transplant in three and hepatectomy in eight), including 10 treated with TARE and one with sorafenib. TARE was more effective than sorafenib in downstaging patients to surgery, achieving a mean survival of 54 months. In the 54 patients without downstaging after treatment, of whom 31 were treated with TARE and 23 with sorafenib, median survival was 20.3 and 9.1 months, respectively (P = 0.001), with different 1-, 2- and 3-year OS rates (64.5%, 42.6% and 37.3% vs 39.1%, 13.0% and 0%). Both propensity score and Bayesian model averaging confirmed an improvement in overall survival in the TARE group compared with sorafenib treatment. CONCLUSIONS: TARE was more effective than sorafenib in downstaging patients with HCC to surgery, providing a significant improvement in survival. Even in patients who were not downstaged to surgery, survival appeared to be superior with TARE over sorafenib.

The role of cosubstrate and mixing on fungal biofilm efficiency in the removal of tannins.

Tannins are polyphenolic compounds produced by plants and they are used in industrial vegetable tanning of leather. Tannins represent one of the low biodegradability substances in tannery wastewaters with high recalcitrant soluble chemical oxygen demand, furthermore high concentration of tannins can inhibit biological treatment. In the present study, four novel rotating submerged packed bed reactors were inoculated with a selected fungal strain to reach a biological degradation of tannins in non-sterile conditions. The selected fungal strain, Aspergillus tubingensis MUT 990, was immobilised in polyurethane foam cubes carriers and inserted inside a submerged rotating cage reactors. The reactors were feed with a solution composed of four tannins: Quebracho (Schinopsis spp.), Wattle (Mimosa spp.), Chestnut (Castanea spp.) and Tara (Caesalpinia spp.). Four reactors with a volume of 4 L each were used, the co-substrate was pure malt extract, the hydraulic retention time was 24 h and the pH setpoint was 5.5. The reactors configuration was chosen to allow the study of the effect of rotation and the co-substrate addition on tannins removal. The experiment lasted two months and it was achieved 80% of chemical oxygen demand and up to 90% dissolved organic carbon removal, furthermore it was detected an important tannase activity.

Exenatide regulates pancreatic islet integrity and insulin sensitivity in the nonhuman primate baboon Papio hamadryas.

The glucagon-like peptide-1 receptor agonist exenatide improves glycemic control by several and not completely understood mechanisms. Herein, we examined the effects of chronic intravenous exenatide infusion on insulin sensitivity, ß cell and α cell function and relative volumes, and islet cell apoptosis and replication in nondiabetic nonhuman primates (baboons). At baseline, baboons received a 2-step hyperglycemic clamp followed by an l-arginine bolus (HC/A). After HC/A, baboons underwent a partial pancreatectomy (tail removal) and received a continuous exenatide (n = 12) or saline (n = 12) infusion for 13 weeks. At the end of treatment, HC/A was repeated, and the remnant pancreas (head-body) was harvested. Insulin sensitivity increased dramatically after exenatide treatment and was accompanied by a decrease in insulin and C-peptide secretion, while the insulin secretion/insulin resistance (disposition) index increased by about 2-fold. ß, α, and δ cell relative volumes in exenatide-treated baboons were significantly increased compared with saline-treated controls, primarily as the result of increased islet cell replication. Features of cellular stress and secretory dysfunction were present in islets of saline-treated baboons and absent in islets of exenatide-treated baboons. In conclusion, chronic administration of exenatide exerts proliferative and cytoprotective effects on ß, α, and δ cells and produces a robust increase in insulin sensitivity in nonhuman primates.

Coordinated defects in hepatic long chain fatty acid metabolism and triglyceride accumulation contribute to insulin resistance in non-human primates.

UNLABELLED: Non-alcoholic fatty liver disease (NAFLD) is characterized by accumulation of triglycerides (TG) in hepatocytes, which may also trigger cirrhosis. The mechanisms of NAFLD are not fully understood, but insulin resistance has been proposed as a key determinant. AIMS: To determine the TG content and long chain fatty acyl CoA composition profile in liver from obese non-diabetic insulin resistant (IR) and lean insulin sensitive (IS) baboons in relation with hepatic and peripheral insulin sensitivity. METHODS: Twenty baboons with varying grades of adiposity were studied. Hepatic (liver) and peripheral (mainly muscle) insulin sensitivity was measured with a euglycemic clamp and QUICKI. Liver biopsies were performed at baseline for TG content and LCFA profile by mass spectrometry, and histological analysis. Findings were correlated with clinical and biochemical markers of adiposity and insulin resistance. RESULTS: Obese IR baboons had elevated liver TG content compared to IS. Furthermore, the concentration of unsaturated (LC-UFA) was greater than saturated (LC-SFA) fatty acyl CoA in the liver. Interestingly, LC-FA UFA and SFA correlated with waist, BMI, insulin, NEFA, TG, QUICKI, but not M/I. Histological findings of NAFLD ranging from focal to diffuse hepatic steatosis were found in obese IR baboons. CONCLUSION: Liver TG content is closely related with both hepatic and peripheral IR, whereas liver LC-UFA and LC-SFA are closely related only with hepatic IR in non-human primates. Mechanisms leading to the accumulation of TG, LC-UFA and an altered UFA: LC-SFA ratio may play an important role in the pathophysiology of fatty liver disease in humans.