A Computational Fluid Dynamics Investigation of a Flapping Hydrofoil as a Thruster.

The paper features a computational fluid dynamics study of a flapping NACA0015 hydrofoil moving with a combination of sinusoidal heaving and pitching. Several kinematic configurations are explored, varying sequentially pitch and heave amplitude, Strouhal number and phase angle, in an attempt to determine the influence of each parameter on the propulsive performance. To optimize efficiency the angle of attack should assume the highest value that also avoids the arise of the leading edge vortex generated in the dynamic stall state. At low Strouhal number optimum is reached at high heave amplitudes, which correspond to the configurations minimizing the hysteresis in the (Cy,Cx) plane. The same outcome in terms of hysteresis minimization has been verified to occur when optimal phase shift was considered. Differently, when the Strouhal number and the angle of attack become higher, to exploit efficiently the lift increment owed to dynamic stall it emerged the necessity of adopting low heave amplitude to improve separation resistance, avoiding the occurrence of deep stall.

Diagnostic performance of image-guided vacuum-assisted breast biopsy after neoadjuvant therapy for breast cancer: prospective pilot study.

BACKGROUND: Image-guided vacuum-assisted breast biopsy (VABB) of the tumour bed, performed after neoadjuvant therapy, is increasingly being used to assess residual cancer and to potentially identify to identify pathological complete response (pCR). In this study, the accuracy of preoperative VABB specimens was assessed and compared with surgical specimens in patients with triple-negative or human epidermal growth factor receptor 2 (HER2)-positive invasive ductal breast cancer after neoadjuvant therapy. As a secondary endpoint, the performance of contrast-enhanced MRI of the breast and PET-CT for response prediction was assessed. METHODS: This single-institution prospective pilot study enrolled patients from April 2018 to April 2021 with a complete response on imaging (iCR) who subsequently underwent VABB before surgery. Those with a pCR at VABB were included in the primary analysis of the accuracy of VABB. The performance of imaging (MRI and PET-CT) was analysed for prediction of a pCR considering both patients with an iCR and those with residual disease at postneoadjuvant therapy imaging. RESULTS: Twenty patients were included in the primary analysis. The median age was 44 (range 35-51) years. At surgery, 18 of 20 patients showed a complete response (accuracy 90 (95 per cent exact c.i. 68 to 99) per cent). Only two patients showed residual ductal intraepithelial neoplasia of grade 2 and 3 respectively. In the secondary analysis, accuracy was similar for MRI and PET-CT (77 versus 78 per cent; P = 0.76). CONCLUSION: VABB in patients with an iCR might be a promising method to select patients for de-escalation of surgical treatment in triple-negative or HER2-positive breast cancer. The present results support such an approach and should inform the design of future trials on de-escalation of surgery.

Cardiac magnetic resonance predictors of left ventricular remodelling following acute ST elevation myocardial infarction: The VavirimS study.

BACKGROUND: Left ventricular (LV) remodelling (REM) ensuing after ST-elevation myocardial infarction (STEMI), has typically been studied by echocardiography, which has limitations, or cardiac magnetic resonance (CMR) in early phase that may overestimate infarct size (IS) due to tissue edema and stunning. This prospective, multicenter study investigated LV-REM performing CMR in the subacute phase, and 6 months after STEMI. METHODS AND RESULTS: patients with first STEMI undergoing successful primary angioplasty were consecutively enrolled. CMR was done at 30-days and 6-months. Primary endpoint was prevalence at 6 months of LV-REM [≥12% increase in LV end-diastolic volume index (LV-REMEDV)]; LV-REM by end-systolic volume index increase ≥12% (LV-REMESV) was also calculated. Of 325 patients enrolled, 193 with a full set of research-quality CMR images were analyzed. LV-REMEDV and LV-REMESV were present in 36/193 (19%) and 34/193 (18%) patients, respectively. At follow up, LV ejection fraction (EF) improved in patients with or without LV-REMEDV, whilst it decreased in those with LV-REMESV (p < 0.001 for interaction). Considering predictors of LV-REM, IS in the highest tertile was clearly separated from the two lower tertiles. In LV-REMEDV, the highest tertile was associated with significantly higher LV-EDV, LV-ESV, and lower EF. CONCLUSIONS: In a contemporary cohort of STEMI patients studied by CMR, prevalence of LV-REMEDV was lower than previously reported. Importantly, our data indicate that LV-REMEDV might not be "adverse" per se, but rather "compensatory", being associated with LV-EF improvement at follow-up. Conversely, LV-REMESV might be an "adverse" phenomenon associated with decreased LV-EF, driven by IS.

A propensity score-matched analysis of breast-conserving surgery plus whole-breast irradiation versus mastectomy in breast cancer.

PURPOSE: Recent observations regarding long-term outcomes among patients with early-stage breast cancer (BC) who underwent breast-conserving surgery (BCS) plus whole-breast irradiation (WBI) or mastectomy are from a small number of registry-based studies. Therefore, these findings may overestimate differences in survival between the two groups, compared with randomized controlled trials conducted in the 1980s. The aim of this study is to compare long-term outcomes and clinicopathologic characteristics between patients treated with BCS + WBI or mastectomy for BC. METHODS: We performed a propensity score-matched analysis in a cohort of 9710 patients aged < 70 years who underwent BCS + WBI or mastectomy without external radiotherapy for a first primary BC (pT1-2, N0-3a) at the European Institute of Oncology between 2000 and 2008. Patients were matched by propensity score. RESULTS: Median follow-up was 8.4 years (interquartile range 6.5-10.2). The cumulative incidence of axillary lymph node recurrence at 10 years was lower in the BCS + WBI group [2.4% (95% CI, 1.7-3.3%)] than in the mastectomy group [4.4% (95% CI, 3.5-5.5%)] (P = .0005), and the cumulative incidence of contralateral BC was higher in the BCS + WBI group [3.9% (95% CI, 2.8-5.1%)] than in the mastectomy group [2.5% (95% CI, 1.7-3.4%)] (P = .01). Among the 366 patients with HER2 subtype BC, BCS + WBI was associated with a fivefold higher risk [hazard ratio 4.97 (95% CI, 2.28-10.8)] of  ipsilateral breast tumor recurrence (IBTR), compared with mastectomy (P < .0001); however, among patients with other BC subtypes, the rates of IBTR were not statistically significantly different. CONCLUSION: Patients with HER2 subtype BC (T1-2, N0-3) who underwent BCS + WBI had a statistically significantly higher risk of IBTR than patients who underwent mastectomy. Survival was not statistically significantly different between the groups.

Breast Cancer Surgery: New Issues.

Since ancient times, breast cancer treatment has crucially relied on surgeons and clinicians making great efforts to find increasingly conservative approaches to cure the tumor. In the Halstedian era (mid-late 19th century), the predominant practice consisted of the radical and disfiguring removal of the breast, much to the detriment of women's psycho-physical well-being. Thanks to enlightened scientists such as Professor Umberto Veronesi, breast cancer surgery has since impressively progressed and adopted a much more conservative approach. Over the last three decades, a better understanding of tumor biology and of its significant biomarkers has made the assessment of genetic and molecular profiles increasingly important. At the same time, neo-adjuvant treatments have been introduced, and great improvements in genetics, imaging technologies and in both oncological and reconstructive surgical techniques have been made. The future of breast cancer management must now rest on an ever more precise and targeted type of surgery that, through an increasingly multidisciplinary and personalized approach, can ensure oncological radicality while offering the best possible quality of life.

Stochastic modelling of solute mass discharge to identify potential source zones of groundwater diffuse pollution.

In heavily urbanised areas, groundwater diffuse pollution is recognised as one of the most insidious threats to groundwater quality. Diffuse pollution originates from multiple small sources releasing a low contaminant mass over a relatively large area; the lack of a defined plume in groundwater, the limited leaked mass, and the fact that leakage may have occurred in the past and be now ceased, make these sources difficult to locate and characterise. In addressing this environmental issue, an inverse approach based on the Null space Monte Carlo stochastic method has been applied in the framework of an innovative methodology with the aim to locate potential source areas distributed in a large (120 km2) urban area. To simplify the problem and better understand the limitations and effectiveness of the proposed methodology, the analysis has been performed using a groundwater model with fixed (i.e., determined by a previous calibration) hydraulic conductivity and flow boundary conditions. The only source of uncertainty considered in the study is the PCE mass discharge from all model cells of the topmost layer. After implementing and calibrating a deterministic solute transport model, multiple random realisations of mass discharge fields were generated, all of which are history-match constrained and hydrogeologically plausible. The obtained stochastic parameter sets were used to investigate the statistical distribution of the solute mass discharge and map the areas that are more likely to host unknown sources of PCE. Although the application of the NSMC stochastic method on the synthetic case study has provided promising results, it has also highlighted that multiple sources of uncertainty (e.g., continuity and duration of each source, attenuation processes) could adversely affect the reliability of the results in a real-world context, in which the effect of other uncertain parameters (hydraulic conductivity amongst all) would need to be considered in addition. This study offers new insights to the problem of aquifer diffuse pollution by providing key information on the potential source zones and on the areas that urgently need to be prioritised for further investigations.

Pretreatment Primary Tumor Stage is a Risk Factor for Recurrence in Patients with Esophageal Squamous Cell Carcinoma Who Achieve Pathological Complete Response After Neoadjuvant Chemoradiotherapy.

BACKGROUND: Although pathological complete response (pCR) after multimodal treatment for esophageal cancer is associated to the best prognosis, recurrence may occur in 20-40% of cases. The present study investigated the recurrence pattern and predictive factors of recurrence after pCR in patients with esophageal cancer. METHODS: In this study, 427 patients received preoperative treatment for either esophageal squamous cell carcinoma (SCC) or adenocarcinoma at Verona University Hospital between 2000 and 2018. Of these, 145 patients (34%) achieved a pCR. Long-term prognosis, recurrence pattern, and risk factors for relapse in pCR patients were analysed. RESULTS: During a median follow-up of 52 months, 37 relapses (25.5%) occurred, mostly at distant level (n = 28). Nearly all locoregional relapses (8/9) were detected in SCC cases. The 5-year overall survival and cancer-related survival were 71.7% (95% confidence interval [CI] 62.6-78.9%) and 77.5% (95% CI 68.5-84.2%) respectively. Male sex, higher body mass index, and cT4 were significant risk factors for recurrence at univariate analysis. The multivariate analysis confirmed the role of cT4 as predictor of recurrence only in SCCs. CONCLUSIONS: Esophageal cancer recurs in about one-fourth of pCR cases. A fair number of local recurrences occurs in SCCs, but the main problem is the systemic disease control. According to our analysis, SCCs patients with cT4 stage have an increased risk to recur, so they should be managed differently by a personalized approach in terms of adjuvant treatment and follow-up.

Effect of Pyloroplasty on Gastric Conduit Emptying and Patients' Quality of Life After Ivor Lewis Esophagectomy.

Background: Delayed gastric emptying (DGE) is a common complication after esophagectomy with gastric tube reconstruction. It is still unclear whether a pyloric drainage procedure might reduce the risk of DGE. Methods: We identified in our database all patients subjected to Ivor Lewis esophagectomy after neoadjuvant chemoradiotherapy in the period 2000-2012. In the period 2000-2009, we performed a routine pyloroplasty (pyloroplasty group, PP group, 15 patients), after 2009 we did not perform any type of pyloric drainage procedure (nonpyloroplasty group, NPP group, 11 patients). We compared the groups with subjective questionnaires to assess the perceived quality of life (QoL) (QLQ-C30 and OES-18) and with objective test to study the gastric tube emptying (timed barium swallow test, scintigraphy, 24 hours' pH-metry). Results: No difference was observed in questionnaires QLC-C30 and OES-18 scores: 73% of patients in PP group and 63% in NPP group scored their overall QoL as good to excellent (QLC-C30). We did not report difference in timed barium swallow test results and in scintigraphy results. Twenty-four-hour pH-metry results showed in PP group a nonsignificant higher number of acid reflux episodes (NPP group 23.2 ± 9.5 versus PP group 41.3 ± 10.7, P = .29) and a longer time with pH <4 (NPP group 0.89% ± 1.6% versus PP group 3.1% ± 2.1%, P = .24). Conclusions: In our series, pyloroplasty was not associated with improved long-term QoL nor with better gastric conduit emptying. Further studies are needed to confirm these findings.

PCE point source apportionment using a GIS-based statistical technique combined with stochastic modelling.

To meet the continuous growth of urbanised areas with the ever-increasing demand for safe water supplies, the implementation of new scientifically based methodologies can represent a key support for preventing groundwater quality deterioration. In this study, a new combined approach based on the application of the Weights of Evidence and the Null-Space Monte Carlo particle back-tracking methods was set up to assess tetrachloroethylene (PCE) contamination due to Point Sources in the densely urbanised north-eastern sector of the Milano FUA (Functional Urban Area). This combined approach offers the advantage of further enhancing the power of each individual technique by integrating both the advective transport mechanism, neglected by the Weights of Evidence, and the influence of specific factors, such as the land use variation, not considered by the Null-Space Monte Carlo particle tracking. To accurately test and explore the performance of this new approach, the analysis was carried out based on the simulation of synthetic PCE plumes using a groundwater numerical model already implemented in a previous study. The Weights of Evidence method revealed that the areas characterised by a groundwater depth lower than 17 m, a groundwater velocity higher than 2.6 × 10-6 m/s, a recharge higher than 0.26 m/y and a significant variation of the industrial activities extent are the most susceptible to groundwater pollution. The Null-Space Monte Carlo particle back-tracking has proved to be effective in delineating the potential source zones and contaminant travel path. The proposed approach can offer additional insights for the protection of groundwater resource. The end-product provides crucial information on the zones that require to be prioritised for investigations and can be easily understood by non-expert decision-makers constituting an advanced tool for enhancing groundwater protection strategies.

Feasibility and safety of an enhanced recovery protocol (ERP) for upper GI surgery in elderly patients (≥ 75 years) in a high-volume surgical center.

Enhanced recovery protocols (ERP) have demonstrated their efficacy after esophagectomy and gastrectomy but little is known about their feasibility and safety in elderly patients. Patients submitted to Ivor-Lewis esophagectomy or gastrectomy for cancer between January 2016 and June 2019 were divided into three age groups: young-age group, YG (≤ 65 years, n = 130); middle-age group, MG (66-74 years, n = 101); old-age group, OG (≥ 75 years, n = 74). The groups were compared for adherence to our ERP, morbidity and mortality rates. After esophagectomy, adherence to ERP was comparable between the three groups, overall morbidity was higher in OG, without statistically significant difference, while the incidence of cardiac complications was significantly higher in OG (p = 0.02). After gastrectomy, OG presented a lower adherence to urinary catheter removal and to early mobilization. No difference in overall morbidity rate was observed (p = 0.13). The median length of stay was comparable both after esophagectomy (p = 0.075) and gastrectomy (p = 0.07). Multivariable analysis showed that age ≥ 75 years was not associated with a higher risk of ERP failure either after esophagectomy (p = 0.59) or after gastrectomy (p = 0.83). After esophagectomy, the risk of failure of the ERP program was higher for patients with ASA grade 3-4 (p = 0.03) and for those with postoperative complications (p < 0.001) while after gastrectomy only postoperative complications were associated to higher risk of ERP failure (p < 0.001). In our series, adherence to ERP protocol of patients ≥ 75 years old was similar to that of younger patients after esophagectomy and gastrectomy, without a significant increase in morbi-mortality rates.

De-escalating dual antiplatelet therapy in patients with acute coronary syndromes: the right strategy to harmonize time-dependent ischemic and bleeding risk in elderly patients?

: The European Society of Cardiology guidelines for myocardial revascularization state that de-escalation of P2Y12 inhibitor treatment guided by platelet function testing may be considered for acute coronary syndrome (ACS) patients deemed unsuitable for 12-month potent platelet inhibition. De-escalation strategy aim is to harmonize the time-dependency of thrombotic risk, which is high in the first month after ACS, then decreases exponentially, with bleeding risk, which tends to remain more stable after the procedure-related peak. Harmonizing time-dependency of clinical events may be particularly relevant in those at high risk, such as the elderly patients with ACS in whom an individualized antiplatelet therapy may be more appropriate than a 'one-size-fits all' approach. In this review, we outline the current medical evidence on the topic of dual antiplatelet therapy de-escalation. In addition, we include insights from the Elderly ACS 2 study and recently published post-hoc analyses conducted by the authors' consortium, which further expands current knowledge.

Assessing bleeding in acute coronary syndrome using the Bleeding Academic Research Consortium definition.

BACKGROUND: The Bleeding Academic Research Consortium (BARC) definition was proposed to overcome the heterogeneity among the many bleeding definitions. The aim of this study-level meta-analysis was to explore the incidence of BARC-assessed bleeding in acute coronary syndrome (ACS) studies and to ascertain the relation between these events and variables related to bleeding risk. METHODS AND RESULTS: We searched the literature for studies that reported bleeding events according to BARC criteria in ACS patients. An analysis on heterogeneity between studies in bleeding reports was performed with I test. A meta-regression was conducted to explore the relation between different types of BARC bleedings and patient and procedural features. Nine studies were included in the analysis. Overall, BARC 2 rates were higher than BARC 3 or 5 rates (6.3 versus 2.6%). An extremely high level of heterogeneity was detected both for BARC 2 (I 99.3%) and BARC 3 or 5 (I 97.5%) bleedings. Increasing age [ß coefficient 0.4% (0.2-0.6%); P < 0.001] and renal impairment [ß coefficient 1 6.5% (1-32.1%); P = 0.037] were associated with increased BARC 3 or 5 rates, whereas the use of glycoprotein IIb/IIIa inhibitors was the only factor related to an increased incidence of BARC 2 bleeding [ß coefficient 2 2.3% (5.5-39%); P = 0.009]. CONCLUSION: The high level of heterogeneity in BARC bleeding reports only partially explained by bleeding risk profile suggests that a regulatory guidance to properly evaluate bleedings and to estimate the risk--benefit in clinical trials investigating different antithrombotic treatments in ACS patients is needed.

Percutaneous coronary interventions for stable ischemic heart disease in Italy.

AIMS: Although the benefits of percutaneous coronary interventions (PCIs) in patients with stable chronic ischemic heart disease (SIHD) are controversial, a large number of PCIs are currently performed in SIHD patients, frequently after coronary angiography (ad-hoc procedures), without the use of fractional flow reserve (FFR) to identify patients most likely to benefit from PCI. METHODS: Assessment of regional variations in PCI for SIHD performed in Italy in 2017 and correlation of the regional number of PCI per million inhabitants with the use of FFR were performed using the data reported in the registry of the Italian Society of Interventional Cardiology (SICI-GISE) registry for the year 2017. RESULTS: PCI for SIHD accounted for 44.5% of all PCI performed in Italy with large variations among the Italian regions. There was a significant and inverse relationship between the use of FFR and the PCI number per million inhabitants performed for SIHD in the various Italian regions (P = 0.01). In the Veneto region, where local authorities mandated Heart Team reports to select the most appropriate treatment choice in multivessel disease patients, the rate of ad-hoc procedures was significantly lower than the national average. CONCLUSION: PCI for SIHD patients represent almost half of all procedures currently performed in Italy with regional variations inversely related to physiologic guidance use. The mandatory assessment by the Heart Team to select the most appropriate treatment choice in multivessel disease patients is associated with a significantly lower number of ad-hoc procedures.

Validation of a new score for outcome prediction in patients with heart failure with reduced ejection fraction.

BACKGROUND: Most models for outcome prediction in heart failure are under-utilized because complex or including non-routine clinical use variables. We aimed to develop a prognostic score for patients with stable heart failure, including only easily obtainable parameters. METHODS: In 376 outpatients with heart failure (ejection fraction ≤40%), twelve variables were individually correlated with 5-year mortality. Those resulted significant predictors of cardiac and overall mortality were used to obtain a risk score. It was validated on a different sample of 325 patients previously enrolled in other clinical studies, according to tertiles of score. RESULTS: Previous acute decompensated heart failure, atrial fibrillation, ejection fraction <30%, not-taking beta-blockers, chronic renal failure were the variables included in the final model. There was a significant difference in 5-year cardiac (P=0.004) and all-cause (P=0.003) mortality risk. Compared to the first tertile of the score, the second tertile and the third tertile had an increasing risk for cardiac cause admission (respectively, HR: 2.7; 95% CI: 1.5-4.9 and HR: 3.2; 95% CI: 1.7-6.1) and for heart failure worsening hospitalization (HR:4.3; 95% CI: 1.3-14.5 and HR: 3.8; 95% CI: 1.03-14.1) as well as the third tertile (respectively, HR:3.2; 95% CI: 1.7-6.1 and HR:3.8; 95% CI: 1.03-14.1.). CONCLUSIONS: Our prognostic model, named OSR HF Risk Score, is a simple, quick, inexpensive tool for predicting patient outcome in 5 years. It might be used as an adjunctive tool in outpatients evaluation alongside more complex scores.

Groundwater diffuse pollution in functional urban areas: The need to define anthropogenic diffuse pollution background levels.

Groundwater status in highly urbanized areas is particularly affected by anthropogenic influence due to diffuse pollution deriving from many sources. This makes very often challenging to determine whether the observed groundwater conditions are the result of localized pollutant sources (PS-Point Sources). In the EU legislative framework it is accepted that, when Natural Background Levels (NBLs) of undesirable elements are proven to be higher than specific Groundwater Quality Standards (GQSs), NBLs should be assumed as GQSs. No procedure is instead defined when anthropogenic Diffuse Pollution Background levels (DBPLs) are higher than GQSs and make unfeasible any remediation strategy. Among the many contaminants affecting groundwater, the chlorinated solvents, tetrachloroethylene (PCE), trichloroethylene (TCE) and trichloromethane (TCM) among the organics and hexavalent chromium, among the inorganics, having been widely used in several industries all over Europe, are very often the most prevalent contaminants in soil and groundwater. Aim of this paper is to discuss a multivariate statistical approach to address the issue of identification of anthropogenic Diffuse Pollution Background Levels. With such aim, an area of about 1600 km2, including the Functional Urban Area of Milan, was considered and 10 independent geochemical datasets, provided by local and regional agencies, and covering the period 2003-2014 were merged into a single database after homogenization and multiple quality checks. A total of 618,258 chemical analyses from 3477 sampling wells were considered, being all samples collected and analyzed through internally consistent protocols. The analysis enabled to identify five main clusters, having specific hydrogeological characteristics, different temporal profiles and pollutant background concentration levels, which were also found to respond differently to meteo-climatic changes. This study offers a robust knowledge basis for drafting a diffuse pollution management plan of the area.

37Cl-compound specific isotope analysis and assessment of functional genes for monitoring monochlorobenzene (MCB) biodegradation under aerobic conditions.

A laboratory approach was adopted in this study to explore the potential of 37Cl-CSIA in combination with 13C-CSIA and Biological Molecular Tools (BMTs) to estimate the occurrence of monochloroenzene (MCB) aerobic biodegradation. A new analytical method for 37Cl-CSIA of MCB was developed in this study. This methodology using a GC-IRMS allowed to determine δ37Cl values within an internal error of ±0.3‰. Samples from a heavily MCB contaminated site were collected and MCB aerobic biodegradation microcosms with indigenous cultures in natural and enhanced conditions were set up. The microcosms data show a negligible fractionation for 13C associated to MCB mass decrease of >95% over the incubation time. Conversely, an enrichment factor of -0.6±0.1‰ was estimated for 37Cl, which is a reflection of a secondary isotope effect. Moreover, the dual isotope approach showed a pattern for aerobic degradation which differ from the theoretical trend for reductive dehalogenation. Quantitative Polymerase Chain Reaction (qPCR) results showed a significant increase in todC gene copy number with respect to its initial levels for both natural attenuation and biostimulated microcosms, suggesting its involvement in the MCB aerobic degradation, whereas phe gene copy number increased only in the biostimulated ones. Indeed, 37Cl fractionation in combination with the dual carbon­chlorine isotope approach and the todC gene copy number represent valuable indicators for a qualitative assessment of MCB aerobic biodegradation in the field.