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Purpose To assess the percentage of computed tomography pulmonary angiography (CTPA) procedures that could have been avoided by methodical application of the Revised Geneva Score (RGS) coupled with age-adjusted D-dimer cut-offs rather than only clinical judgment in Emergency Department patients with suspected pulmonary embolism (PE). Material and methods Between November 2019 and May 2020, 437 patients with suspected PE based on symptoms and D-dimer test were included in this study. All patients underwent to CTPA. For each patient, we retrospectively calculated the age-adjusted D-dimer cut-offs and the RGS in the original version. Finally, CT images were retrospectively reviewed, and the presence of PE was recorded. Results In total, 43 (9.84%) CTPA could have been avoided by use of RGS coupled with age-adjusted D-dimer cut-offs. Prevalence of PE was 14.87%. From the analysis of 43 inappropriate CTPA, 24 (55.81%) of patients did not show any thoracic signs, two (4.65%) of patients had PE, and the remaining patients had alternative thoracic findings. Conclusion The study showed good prevalence of PE diagnoses in our department using only physician assessment, although 9.84% CTPA could have been avoided by methodical application of RGS coupled with age-adjusted D-dimer cut-offs.

Purpose: Skeletal muscle mass (SMM) depletion and sarcopenia as predictors of postoperative complications and poorer overall survival (OS) have been validated in many surgical fields through cross-sectional imaging (CT, MRI), with potential limitations. We evaluated it in a stage III–IV head and neck squamous cell carcinoma (HNSCC) surgical cohort through ultrasound (US) of rectus femoris muscle (RF), a quick, cheap, repeatable alternative. Methods: Patients submitted to surgical treatment with curative purpose were recruited and prospectively evaluated through clinical, biometric, biochemical, surgical, pathological and functional prognosticators and with preoperative US of RF with regards to 30-day complications and OS. Results: Forty-seven patients completed the study. RF cross-sectional area (RF-CSA) was used to identify patients with low SMM (CSA ≤ 0.97cm2: 18/47, 38.3%). RF-CSA was lower in complicated cases (0.95 ± 0.48 vs 1.41 ± 0.49cm2; p = 0.003), remaining the only independent predictor of postoperative complications at multivariate analysis, with a model including ASA score and modified Frailty index (OR 9.84; p = 0.004). SMM depletion significantly impaired OS (13.6 ± 2.9 vs 26.3 ± 2.1months; p = 0.017), being its only independent prognosticator at multivariate Cox regression analysis (OR 4.42; p = 0.033). Conclusion: RF-CSA, evaluated with US, seems a reliable method for identification of patients with low SMM in a stage III–IV HNSCC cohort, defining a subset at high-risk of 30-day complications and poorer OS.

The Transplant Centers belonging to Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO) conducted a survey with the aim of evaluating the effect of SARS-CoV2 pandemic on the allogeneic transplant activity in Italy. The pandemic period from 1/3/2020 to 31/7/2020 was compared with the same period in 2019. Overall, in 2020 there was a 2.4% reduction in the number of allo-HCT cases compared to 2019. Interestingly, this deflection did not affect the acute leukemia cases (+5.7% in 2020). The use of peripheral blood-derived stem cells (+10.7%) and cryopreservation (97.4% of the centers) was highly adopted in 2020. Despite the sanitary emergency, almost all of the surveyed centers declared no impact of SARS-CoV2 pandemic on the transplant timing and outcomes, and the sanitary policy was positively evaluated by the majority of centers. The emergency measures ensured that only a minority of the allo-HCT patients had been infected by SARS-CoV2; however, a mortality of 42.1% among the allo-HCT patients hospitalized for COVID-19 was recorded. This survey gives us the information that the GITMO Group reacted positively to the pandemic. Thanks to the emergency strategies, the Italian allo-HCT activity continued safely, showing only a minor deflection and offering the same probability of cure to the transplanted patients.

Highlights • Mesenteric lipodystrophy is a rare fibroinflammatory disease of unknown origin. • The detection of mesenteric lipodystrophy is challenging and requires early clinical suspicion. • Clinical and imaging findings can mimick other pathological conditions affecting the mesenteric fat tissue. • Contrast enhanced CT is the most accurate imaging technique for diagnosing mesenteric lipodystrophy., Introduction Mesenteric lipodystrophy is a rare fibroinflammatory disease of unknown origin with clinical and radiological non specific findings. Presentation of the case The case of a 42-years-old man affected by a pedunculated mesenteric lipodystrophy mimicking Meckel’s diverticulum is reported. Clinical, imaging and histological findings are discussed. Discussion Mesenteric lipodystrophy affects the mesenteric fat of the abdomen with a typical diffuse thickening of the mesentery, nodular thickening of the mesenteric root and presence of mass-like lesions. Ultrasound (US) and Multiphasic Computed Tomography (CT) represent the main imaging tools used for diagnosis. Clinical and imaging findings can mimick other pathological conditions affecting the mesenteric fat tissue. Contrast enhanced CT is the most accurate imaging technique for diagnosing mesenteric lipodystrophy due to the high panoramicity and accuracy with multiplanar imaging. Multiphasic technique helps to characterize the lesion and to recognize vascular anatomy. Oral administration of iodinated contrast medium may help to assess the relationship with bowel loops. All these diagnostic elements are crucial for the surgical timing and approach. Conclusions Due to the heterogeneous mesenteric involvement, the nonspecific CT findings and the high number of diseases for differential diagnosis, the detection of mesenteric lipodystrophy is challenging and requires early clinical suspicion. An histological examination is always necessary.

Glaucoma is a neurodegenerative disease, our study aimed to evaluate the potential effects of Palmitoylethanolamide (PEA) supplementation on RGCs function by PERG examination, and to record effects on intraocular pressure, visual field and quality of life. It was a single centre, randomized, prospective, single blind, two treatment, two period crossover study on stable glaucoma patients on topical monotherapy comparing current topical therapy alone or additioned with PEA 600 mg one tablet a day. At baseline, at 4 and at 8 months, all patients underwent to complete ophthalmic examination, pattern electroretinogram, visual field, and quality of life evaluation. 40 patients completed the study: mean age 66.6 ± 7.6 years; 21 (52.5%) male; 35 POAG (87.5%). At baseline, most patients had an early visual field defect, the IOP was well controlled. At the end of the PEA 600 mg supplementation, a significantly higher (mean 0.56 μV, 95% CI 0.30–0.73, p

Background: The onset of chronic kidney disease (CKD) is an important prognostic factor in young adults with congenital heart disease (CHD). Although it is likely that CKD is manifest early in CHD patients, the prevalence among adolescents is still unknown. The National Kidney Foundation’s Kidney Disease Improving Global Outcomes guidelines 2012 recommend new equations for the estimated glomerular filtration rate (eGFR) and highlight the importance of albuminuria for CKD screening. The objective of the present study was to estimate the prevalence of CKD in CHD adolescents. Methods: This observational cross-sectional study included 115 patients aged 10–18 years attending the cardiologic outpatient clinic at our institution as a follow-up after cardiac surgery in infancy related to various CHDs. CKD assessment used the CKD criteria 2012, including eGFR equations based on serum creatinine and cystatin C, and measurement of albuminuria. Results: No patient had an eGFR –1 1.73 m–2. However, 28.7% of all patients (95% CI 20.7–37.9) had eGFRbetween 60 and 89 mL min–1 1.73 m–2 when estimated by the bedside Schwartz creatinine-based equation,and 17.4% (95% CI 11.2–24.1) had eGFRbetween 60 and 89 mL min–1 1.73 m–2 when estimated by the Zappitelli equation, combining creatinine and cystatin C. Of all patients, 20.0% (95% CI 12.1–26.7) had orthostatic proteinuria, and none had persistent albuminuria. Conclusions: There was no evidence of CKD in the present population aged 10–18 years. The significance of an eGFR between 60 and 90 mL min–1 1.73 m–2 is not concordant for this age range and requires further investigations.

Simple Summary The number of druggable tumor-specific molecular alterations in the treatment of non-small cell lung cancer (NSCLC) has grown significantly in the past decade. Emerging technologies such as liquid biopsy and single-cell methods allow for studying targetable drivers and develop personalized treatments. However, although new therapies confer prolonged disease control and high tumor response rates, most patients eventually progress on targeted treatments. Intratumoral heterogeneity is a frequent event in NSCLC, driving the tumor cells to develop adaptive or new resistance mechanisms within the drug environment. This review summarizes the current and upcoming research on the biological role of tumor heterogeneity, highlighting the link between early and acquired drug resistance and tumoral heterogeneity in targetable driver mutated NSCLC. Abstract Tailored therapies based on the identification of molecular targets currently represent a well-established therapeutic scenario in the treatment of non-small cell lung cancer (NSCLC) patients. However, while aiming to improve patients’ response to therapy, development of resistance is frequently observed in daily clinical practice. Intratumoral heterogeneity is a frequent event in NSCLC, responsible for several critical issues in patients’ diagnosis and treatment. Advances in single-cell sequencing technologies have allowed in-depth profiling of tumors and attributed intratumoral heterogeneity to genetic, epigenetic, and protein modification driven diversities within cancer cell populations. This review highlights current research on the biological role of tumor heterogeneity and its impact on the development of acquired resistance in NSCLC patients.

Objectives: To identify and validate baseline magnetic resonance imaging (b-MRI) radiomic features (RFs) as predictors of disease outcomes in effectively cured head and neck squamous cell carcinoma (HNSCC) patients. Materials and methods: Training set (TS) and validation set (VS) were retrieved from preexisting datasets (HETeCo and BD2Decide trials, respectively). Only patients with both pre- and post-contrast enhancement T1 and T2-weighted b-MRI and at least 2years of follow-up (FUP) were selected. The combination of the best extracted RFs was used to classify low risk (LR) vs. high risk (HR) of disease recurrence. Sensitivity, specificity, and area under the curve (AUC) of the radiomic model were computed on both TS and VS. Overall survival (OS) and 5-year disease-free survival (DFS) Kaplan–Meier (KM) curves were compared for LR vs. HR. The radiomic-based risk class was used in a multivariate Cox model, including well-established clinical prognostic factors (TNM, sub-site, human papillomavirus [HPV]). Results: In total, 57 patients of TS and 137 of VS were included. Three RFs were selected for the signature. Sensitivity of recurrence risk classifier was 0.82 and 0.77, specificity 0.78 and 0.81, AUC 0.83 and 0.78 for TS and VS, respectively. VS KM curves for LR vs. HR groups significantly differed both for 5-year DFS (p

Simple Summary The therapeutic strategies employed for anaplastic thyroid cancer patients seems to be insufficient to prolong their survival, but some characteristics could predict a good prognosis, so that, starting from our experience we offer a systematic review of the literature to better understand anaplastic thyroid cancers behavior and their prognostic factors, in order to recognize and select the patients with the higher probability of better outcome even if metastatic. Moreover, we described an uncommon site of metastasis in order to improve scientific knowledge about this rare and highly aggressive pathology. Abstract Anaplastic thyroid carcinoma (ATC) is a very rare, highly aggressive malignant thyroid tumor with an overall survival from 3 to 5 months in most of the cases. Even the modern and intensive treatments seem not to be enough to provide a cure, also for the resectable ones, and the role of chemotherapy is still unclear but does not seem to prolong survival. Nevertheless, some patients survive longer and have a better outcome, even in the presence of metastasis, than what the literature reports. We present the case of a 64-year-old female affected by ATC, treated on February 2018 with surgery followed by chemoradiation. One year after surgery, the patient developed a subcutaneous recurrence that was radically resected and is still alive 29 months after the diagnosis. We propose a systematic review of the literature to deepen the knowledge of the prognostic factors of ATC with the aim to recognize and select the patients with a better outcome, even if metastatic, and to describe a very uncommon site of metastatization.

Paolo Bossi,1 Andrea Antonuzzo,2 Grazia Armento,3 Francesca Consoli,1 Jacopo Giuliani,4 Raffaele Giusti,5 Maurizio Lucchesi,6 Aurora Mirabile,7 Loredana Palermo,8 Sarah Scagliarini9 1Department of Medical Oncology, ASST-Spedali Civili, Brescia, Italy; 2Medical Oncology Unit 1 SSN, Oncology Center, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; 3Department of Medical Oncology, Campus Bio-Medico University Hospital, Rome, Italy; 4Unit Department Medical Oncology, Mater Salutis, Hospital, Legnago, Italy; 5Unit Department Medical Oncology, Sant ‘Andrea University Hospital, Rome, Italy; 6Pneumology Unit - Thoracic Oncology Service, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; 7Department of Oncology, San Raffaele University Hospital, Milan, Italy; 8Unit Department Medical Oncology, IRCCS Giovanni Paolo, Bari, Italy; 9Unit Department Medical Oncology, AORN Cardarelli, Napoli, ItalyCorrespondence: Paolo BossiDepartment of Medical Oncology, ASST-Spedali Civili, Brescia, 1, Brescia, 25123, ItalyTel +39 0303998969Fax +39 0303995072Email paolo.bossi@unibs.itBackground: Despite the prevalence of pain among patients with cancer and the availability of pertinent guidelines, the clinical management of oncological pain is decisively insufficient. To address this issue, we evaluated current trends in clinical practice and subsequently generated a list of ten corrective actions—five things to do and five things not to do—for the diagnosis, management, and monitoring of cancer pain.Methods: The survey included 18 questions about clinical practice surrounding background pain and breakthrough cancer pain (BTcP). Survey questions were developed by a scientific board of 10 physician experts and communicated via email to an expanded panel of physicians in Italy. Responses were tabulated descriptively for analysis.Results: Of 51 invited physicians, 32 (63%) provided complete survey responses. The responses revealed several incongruencies with current guideline recommendations: physicians did not always diagnose or monitor pain using diagnostically validated or disease-specific instruments; frequently based clinical decision-making on time availability or convenience; and pharmacological therapy was often inappropriate (eg, prescribing NSAIDs or corticosteroids for BTcP). The list of corrective actions generated by the scientific board favored a guideline-oriented approach that systematically characterizes oncological pain and implements treatment based on pain characteristics (eg, fast-acting transmucosal opioids for BTcP) and evidence-based recommendations.Conclusion: Oncologists require better education and training about the diagnosis, treatment, and monitoring of oncological pain. Physicians should be aware of current guideline recommendations as well as available pharmacological tools for BTcP.Keywords: cancer pain, pain management, precision medicine, digital medicine

Purpose To evaluate persistence rate on repeated transurethral resection of the bladder (re-TURB) 6 weeks after the first TURB in patients with pT1HG disease undergoing resection of the margins and bed on Narrow Band Imaging. Materials and methods A consecutive series of patients undergoing TURB and a diagnosis of pT1 high grade disease were prospectively enrolled. On initial TURB patients underwent classic white light resection of the tumour followed by narrow band image (NBI) resection of margins and bed. After 6 weeks from the initial TURB, patients underwent a re-TURB under white light. Persistence rates on re-TURB were recorded. Results Overall 797 patients underwent TURB, out of them 126 patients with pT1 high grade disease were included in the study. The total number of lesions was 226 meaning 1.79 lesions per patient. On re-TURB 24/126 (19%) of the patients presented residual disease with a total of 28/226 (12%) lesions identified. All these patients presented a pTa residual disease. Out of them 8/21 (38%) presented bladder cancer on the resection bed and 13/21 (62%) presented bladder cancer on margins. Conclusion Narrow Band Imaging trans-urethral resection of the bladder is an oncological effective procedure in the treatment of pT1HG disease. The procedure has a 19% of persistence rate which is inferior when compared to the available evidence on white light TURB. Further multicenter studies are needed in order to validate our results.

Immunotherapy, and in particular immune-checkpoints blockade therapy (ICB), represents a new pillar in cancer therapy. Antibodies targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) and Programmed Death 1 (PD-1)/Programmed Death Ligand-1 (PD-L1) demonstrated a relevant clinical value in a large number of solid tumors, leading to an improvement of progression free survival and overall survival in comparison to standard chemotherapy. However, across different solid malignancies, the immune-checkpoints inhibitors efficacy is limited to a relative small number of patients and, for this reason, the identification of positive or negative predictive biomarkers represents an urgent need. Despite the expression of PD-L1 was largely investigated in various malignancies, (i.e., melanoma, head and neck malignancies, urothelial and renal carcinoma, metastatic colorectal cancer, and pancreatic cancer) as a biomarker for ICB treatment-patients selection, it showed an important, but still imperfect, role as positive predictor of response only in nonsmall cell lung cancer (NSCLC). Importantly, other tumor and/or microenvironments related characteristics are currently under clinical evaluation, in combination or in substitution of PD–L1 expression. In particular, tumor-infiltrating immune cells, gene expression analysis, mismatch- repair deficiency, and tumor mutational landscape may play a central role in predicting clinical benefits of CTLA-4 and/or PD-1/PD-L1 checkpoint inhibitors. In this review, we will focus on the clinical evaluation of emerging biomarkers and how these may improve the naïve vision of a single- feature patients-based selection.

Purpose: Patients with suprasystemic idiopathic pulmonary hypertension (S-PAH) have a poor prognosis. Therapeutic options are limited. Reverse Potts shunt creation modifies physiology transforming patients with PAH into Eisenmenger physiology with a better outcome. Percutaneous transcatheter stent secured aortopulmonary connection (transcatheter Potts Shunt, TPS) is a feasible very high-risk procedural option in such patients. We report our experience with patients undergoing TPS at our institution requiring extracorporeal membrane oxygenation (ECMO) support. Methods: A prospective observational study of patients with drug-refractory PAH, worsening NYHA class, and right ventricular failure undergoing TPS. Two patients required rescue ECMO for cardiac arrest during the procedure. Subsequently, “standby ECMO” was available in all the following cases and elective support was provided in patients with extremely poor conditions. Results: Ten pediatric patients, underwent TPS at our institution. Two patients were rescued by ECMO after cardiac arrest during the shunt creation. This occurred as a result of the acute loading of the left ventricle (LV) after retrograde aortic arch filling through the Potts shunt. Following this, another two patients underwent elective ECMO after the uneventful induction of anesthesia. They all died postoperatively despite a successful TPS procedure. The causes of death were not related to the use of ECMO, but the complication of severe PAH. Six patients with successful TPS did not require ECMO and survived. Conclusions: TPS is a pioneering procedure offering the opportunity to treat high-risk idiopathic drug-refractory PAH patients. Acute LV failure is a complication of TPS in patients with S-PAH. Elective ECMO, an option to avoid circulatory arrest and acute profound hypoxia secondary to exclusive right-to left shunt systemic perfusion by Potts shunt and LV dysfunction with resulting pulmonary edema, may be used at the early stage of the learning curve, but it does not influence the prognosis of these patients which remains poor.

The traditional cancer drug development pathway is increasingly being superseded by trials that address multiple clinical questions. These are collectively termed Complex Innovative Design (CID) trials. CID trials not only assess the safety and toxicity of novel anticancer medicines but also their efficacy in biomarker-selected patients, specific cancer cohorts or in combination with other agents. They can be adapted to include new cohorts and test additional agents within a single protocol. Whilst CID trials can speed up the traditional route to drug licencing, they can be challenging to design, conduct and interpret. The Experimental Cancer Medicine Centres (ECMC) network, funded by the National Institute for Health Research (NIHR), Cancer Research UK (CRUK) and the Health Boards of Wales, Northern Ireland and Scotland, formed a working group with relevant stakeholders from clinical trials units, the pharmaceutical industry, funding bodies, regulators and patients to identify the main challenges of CID trials. The working group generated ten consensus recommendations. These aim to improve the conduct, quality and acceptability of oncology CID trials in clinical research and, importantly, to expedite the process by which effective treatments can reach cancer patients.

Autologous hematopoietic stem cell transplantation (AHSCT) has been used in the treatment of highly active multiple sclerosis (MS) for over two decades. It has been demonstrated to be highly efficacious in relapsing–remitting (RR) MS patients failing to respond to disease-modifying drugs (DMDs). AHSCT guarantees higher rates of no evidence of disease activity (NEDA) than those achieved with any other DMDs, but it is also associated with greater short-term risks which have limited its use. In the 2019 updated EBMT and ASBMT guidelines, which review the clinical evidence of AHSCT in MS, AHSCT indication for highly active RRMS has changed from “clinical option” to “standard of care”. On this basis, AHSCT must be proposed on equal footing with second-line DMDs to patients with highly active RRMS, instead of being considered as a last resort after failure of all available treatments. The decision-making process requires a close collaboration between transplant hematologists and neurologists and a full discussion of risk–benefit of AHSCT and alternative treatments. In this context, we propose a standardized protocol for decision-making and informed consent process.

This paper focuses on the complex conservation of the multi-material sculpture Love Me (1998) made by the British artist Sarah Lucas. The fragility of the constituent materials, combined with frequent transportations and installation/de-installation in art shows worldwide, had produced a deformation on one leg of the artwork. The goal of this experimental study was to develop a treatment methodology to ease out the dent and find a consolidant able to secure the area from further damage. A novel traction system, borrowed from medical limb-lengthening surgery, was developed and several types of tie rods and protecting layers were tested. Moreover, innovative materials based on nanocellulose particles were evaluated as strengthening agents for the papier-mâche layers and compared to traditional strengthening products. Due to the lack of information obtained from the experimentation, the use of nanocellulose particles was not considered safe for the treatment, which was done using more traditional materials, namely wheat starch and Kozo Japanese paper. Nevertheless, the results of the preliminary trials laid the foundation for the use of these novel products for conservation purposes.

Patients diagnosed with head and neck cancer, besides a potentially life-threatening diagnosis, have to face highly visible disfigurement and disruptions of essential functioning, such as eating, swallowing, breathing, and speech, and have to endure complex and often debilitating treatments such as chemotherapy, radiotherapy, and surgery. One of the most frequent side effects of oncological treatments is pain that often leads to a disruption of quality of life and of psychophysical well-being. Unfortunately, most of clinical trials omit to study these aspects; hence, there is a lack of standardized care protocols. However, a timely and multidisciplinary approach could improve these distresses.

Aim of our study is to compare the surgery outcomes and safety of button bipolar enucleation of the prostate vs. open prostatectomy in patients with large prostates (> 80 g) in a single-centre cohort study. All patients with lower urinary tract symptoms due to benign prostatic enlargement undergoing button bipolar enucleation of the prostate (B-TUEP) or open prostatectomy (OP) between May 2012 and December 2013 were enroled in our study. Data on clinical history, physical examination, urinary symptoms, erectile function, uroflowmetry and prostate volume were collected at 0, 1, 3, 6, 12, 24 and 36 months. Early and long-term complications were recorded. Overall, 240 patients were enroled. Out of them 111 patients (46%) performed an OP and 129 patients (54%) performed a B-TUEP. In terms of efficacy, both procedures showed durable results at three years with a reintervention rate of 7.5% in the OP group and 5% in the B-TUEP group. In terms of safety, B-TUEP presented less high-grade complications when compared with OP. In our single-centre study, B-TUEP represents a valid alternative to OP with excellent outcomes at three years. Further multicentre studies should confirm our results.

Introduction: Understaging after initial transurethral resection is common in patients with high-risk non muscle infiltrating bladder cancer (NMIBC) and can delay accurate diagnosis and definitive treatment. The rate of upstaging from T1 to T2 disease after repeated transurethral resection ranges from 0 to 28%, although the rate of upstaging may be even higher up to 49% when muscularis propria is absent in the first specimen. A restaging classic transurethral resection of bladder tumour (re-cTURBT) is the better predictor of early stage progression. According to some reports, the rate of positivity for tumor in re-cTURBT performed within eight weeks after initial cTURBT was as high as 18-77%, and in about 40% of the patients a change in tumor stage was reported. We aimed to investigate, in high risk group, the presence of residual tumor following white light classical transurethral resection of bladder tumor (WLre-cTURBT) and the different recurrence and progression rate between patients with persistent or negative (pT0) oncological disease after WLre-cTURBT. Materials and methods: A cohort of 285 patients presenting with primitive bladder cancer underwent to WLcTURBT from January 2011 to December 2015; out of them 92 (32.28%) were T1HG. In according to EAU guidelines 2011, after 4-6 weeks all HG bladder cancer patients underwent a WL recTURBT . All patients were submitted to a subsequent followup including cystoscopy every 3 months with multiple biopsies, randomly and in the previous zone of resection; urinary citology on 3 specimens and kidney/bladder ultrasound every 6 months. The average follow-up was 48 months. Results: Following WLre-cTURBT we observed a persistent disease in 18 (15.2%) patients: 14 (77.7%) with a HG-NMIBC and 4 (22.2%) with a high grade (HG) muscle invasive bladder cancer (pT2HG). After follow up of all 92 patients according to the guidelines EAU, we observed recurrence in 36/92 (39.1%) and progression in 14/92 (15.2%). Of 14 NMIBC with persistent disease, 10 patients (71.4%) showed recurrence: 4 patients (40%) were pT1HG with concomitant carcinoma in situ (CIS), 3 patients (30%) multifocal pTaHG, 2 (20%) patients CIS and one patient (10%) a muscle invasive neoplasm (pT2HG). Instead of the group of 48 patients pT0 following WL recTURBT, we observed recurrence in 26 patients (54.1%) and in two patients (4.1%) progressions, who presented after 3 months in association with CIS. The remaining 22 patients (45.9%) with initial pT1HG are still progression free. Multivariate analysis showed that the most important variable of early progression were persistent neoplasm and histopathological findings at WLre-cTURBt (p = 0.01), followed by the Summary No conflict of interest declared. INTRODUCTION Bladder cancer is a common genito-urinary malignancy, with transitional cell carcinoma comprising nearly 90% of all primary bladder tumours. At the first diagnosis 70% to 80% of urothelial tumours are confined to the epithelium, the remainder is characterized by muscle invasion. A significant number of patients with high risk non-muscle invasive bladder tumours (HG-NMIBT) treated with white light classic transurethral resection of bladder tumours (WLcTURBT) and intravesical BCG will progress to invasive disease (1-3). Progression to muscle invasion (pT2) mandates immediate radical cystectomy (4). WLcTURBT is the standard initial therapy for NMIBT, but the high percentage of recurrence after surgery is still an unresolved problem (5). High grade pT1 bladder neoplasm (pT1HG) really represents a therapeutic challenge due to the high risk of progression (about 15-30%) to muscle-invasive disease, usually within 5 years (6). However, no consensus exists regarding the treatment of patients with recurrent bladder tumours that invade the lamina propria (pT1) (7-9). Recent studies suggested that the first cTURBT may be incomplete in a significant number of cases (10). Understaging at the time of the initial transurethral resection is common for patients with high-risk NMIBC and can delay accurate diagnosis and definitive treatment. It is therefore recommended for patients with high-risk disease and in those with large or multiple tumors or when the initial transurethral resection is incomplete, to repeat WLre-cTURBT within 2-6 DOI: 10.4081/aiua.2017.4.272 result of the first cystoscopy (p = 0.002) and presence of CIS (p = 0.02). Discussion: Following WLre-cTURBt in HG-NMIBC patients we identified in 15% of cases a persistent disease with a 4.3% of MIBC. In the high risk persistent bladder neoplasms group we observed recurrent and progression rate higher than in T0 bladder tumours group (Δ = + 17.3% and = Δ + 62.5%, p < 0.05

Background In pediatric cardiac surgery, early extubation has been proved to be a safe and beneficial practice in most situations. However, it is not known if it is feasible in high-risk infants, notably neonates and infants undergoing complex surgical procedures. The aim of the study was to compare the prevalence of early extubation in a population of high-risk infants at two different eras and the factors associated with the duration of mechanical ventilation. Methods We compared two historical matched cohorts of 27 neonates and infants under 1 year of age. One cohort included patients of the year 2014 and the other patients of 2018 and 2019. The main endpoint was early extubation defined as extubation in the first 24 hours (H24) after surgery. We also analyzed hemodynamic variables, inotropic drugs use and presence or absence of delayed sternal closure. Results The duration of mechanical ventilation was significantly shorter in the more recent cohort (median of 40 h versus 69 h in the former cohort), data using the Kaplan–Meier method are presented in Fig. 1, with a log-rank test not significant. The rate of extubation before H24 after surgery, though more elevated, was not significantly different. This was associated with the use of a different inodilator (milrinone in the first era and enoximone in the second era) and a less frequent use of vasopressors. We also observed less delayed sternal closures in the second period (only 2 patients whereas there were 10 patients in the first period). In a subgroup analysis comparing infants without delayed sternal closure, the observed trends were still present but there was no significant difference on the main endpoint and the duration of mechanical ventilation. Conclusion Early extubation after pediatric cardiac surgery in high-risk infants tends to be more prevalent in recent times. Facilitating factors and best practices are not yet precisely defined especially concerning the hemodynamic management of patients.

Baseline clinical prognostic factors for recurrent and/or metastatic (RM) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy are lacking. CT-based radiomics may provide additional prognostic information. A total of 85 patients with RM-HNSCC were enrolled for this study. For each tumor, radiomic features were extracted from the segmentation of the largest tumor mass. A pipeline including different feature selection steps was used to train a radiomic signature prognostic for 10-month overall survival (OS). Features were selected based on their stability to geometrical transformation of the segmentation (intraclass correlation coefficient, ICC > 0.75) and their predictive power (area under the curve, AUC > 0.7). The predictive model was developed using the least absolute shrinkage and selection operator (LASSO) in combination with the support vector machine. The model was developed based on the first 68 enrolled patients and tested on the last 17 patients. Classification performance of the radiomic risk was evaluated accuracy and the AUC. The same metrics were computed for some baseline predictors used in clinical practice (volume of largest lesion, total tumor volume, number of tumor lesions, number of affected organs, performance status). The AUC in the test set was 0.67, while accuracy was 0.82. The performance of the radiomic score was higher than the one obtainable with the clinical variables (largest lesion volume: accuracy 0.59, AUC = 0.55; number of tumoral lesions: accuracy 0.71, AUC 0.36; number of affected organs: accuracy 0.47; AUC 0.42; total tumor volume: accuracy 0.59, AUC 0.53; performance status: accuracy 0.41, AUC = 0.47). Radiomics may provide additional baseline prognostic value compared to the variables used in clinical practice.

Background While lung ultrasonography (LUS) has utility for the evaluation of the acute phase of COVID-19 related lung disease, its role in long-term follow-up of this condition has not been well described. The objective of this study is to compare LUS and chest computed tomography (CT) results in COVID-19 survivors with the intent of defining the utility of LUS for long-term follow-up of COVID-19 respiratory disease. Methods Prospective observational study that enrolled consecutive survivors of COVID-19 with acute hypoxemic respiratory failure (HARF) admitted to the Respiratory Intensive Care Unit. Three months following hospital discharge, patients underwent LUS, chest CT, body plethysmography and laboratory testing, the comparison of which forms the basis of this report. Results 38 patients were enrolled, with a total of 190 lobes analysed: men 27/38 (71.1%), mean age 60.6 y (SD 10.4). LUS findings and pulmonary function tests outcomes were compared between patients with and without ILD, showing a statistically significant difference in terms of LUS score (p: 0.0002), FEV1 (p: 0.0039) and FVC (p: 0.012). ROC curve both in lobe by lobe and in patient's overall analysis revealed an outstanding ILD discrimination ability of LUS (AUC: 0.94 and 0.95 respectively) with a substantial Cohen's coefficient (K: 0.74 and 0.69). Conclusions LUS has an outstanding discrimination ability compared to CT in identifying an ILD of at least mild grade in the post COVID-19 follow-up. LUS should be considered as the first-line tool in follow-up programs, while chest CT could be performed based on LUS findings.

Objective: The aim of this study was to compare, in order to increase our ability to detect bladder cancer, the predictive power of narrow band imaging (NBI) versus white light cystoscopy (WL). The secondary objective was to evaluate how the preoperative use of NBI cystoscopy can increase the ability to detect bladder lesions in terms of status, multi-focality and dimensions. Materials and methods: Between June 2010 and April 2012, 797 consecutive patients, 423 male and 374 female, affected by suspected bladder cancer lesions, underwent to WL plus NBI cystoscopy and subsequently to WL Bipolar Gyrus PK (Olympus, Tokyo, Japan) transurethral resection of bladder tumour (WL-TURBT). The average follow-up was 24 (16-38) months. Mean age was 67.7 yrs. (range 46-88). All the patients underwent by same surgeon to WL resection (WL-TURBT) of the previously identified lesions by same surgeon. All the removed tissue was sent separately for histological evaluation after mapping the areas of resection on a topographic sheet. Results: In our study we considered 797 patients that matched our inclusion criteria. Through the use of WL cystoscopy, we identified 603 patients (75.53%) with suspicious lesions, instead, with the use of light NBI, we found 786 patients with suspicious lesions (98.49%).The use of NBI cystoscopy increases by approximately 30% the specific ability to detect lesions not otherwise visible with WL cystoscopy (OR 21.9 and RR 1.30), in particular for patients with lesions size < 3 cm (OR 24.00; RR 1.40), unifocal (OR: 22.28; RR 1.47) and recurrent (OR 58.4; RR 1.34). Pathology demonstrated the presence of cancer in 512 (64.2%) patients, of whom 412 (51.8%) were visible both with WL cystoscopy and NBI cystoscopy. In our experience, only 11 (1.38%) lesions were only positive at WL cystoscopy (negative at NBI cystoscopy) thus 501 (62.8%, OR 10.13; RR 1.21) patients showed bladder oncological lesions positive at NBI cystoscopy. In these patients, the use the NBI Cystoscopy has better highlighted a recurrence (p < 0.005; OR 22.8, RR 1.23; 95% CI-1.13 to 0.24) or a lesion < 3 cm (p < 0.05; OR 11.4 , RR 1.30; 95% CI-0.18 to 0.29) or a unifocal lesion (p < 0.005; OR 10.38, RR 1.34, CI 0.18 to 0.30). Conclusions: The use of NBI cystoscopy, significantly increases by approximately 30% our predictive power to identify neoplastic lesions, especially unifocal or < 3 cm or recurrent lesions. Following WLTURBT, stage, dimension and focaliity are statistically significant determinants (p < 0.001) of the bladder oncological lesions detected by NBI cystoscopy rather than by WL cystoscopy.

Background The reversed Potts shunt improves right ventricular (RV) function in patients with suprasystemic pulmonary arterial hypertension (PAH). The proximity of the left pulmonary artery (LPA) to the descending aorta (DAo) permits the creation of a transcatheter connection. We sought to assess the safety, feasibility, and hemodynamic efficacy of the transcatheter Potts shunt (TPS) in children. Methods The TPS procedure was performed using radiofrequency energy for vessel perforation and deployment of a covered stent to connect the DAo and LPA. Procedural details and clinical follow-up data were collected prospectively. Results A TPS was successfully created in 6 children (mean age, 11.0 ± 4.2 years) with drug-refractory suprasystemic PAH and deteriorating RV function. All patients exhibited nearly complete equalization of aortic and pulmonary pressures and improvement in RV contractility within days after TPS placement. Two patients with pre-existing severe biventricular dysfunction and pericardial effusion experienced acute low-output states immediately after shunt creation because of sudden reductions in left ventricular (LV) preload, resulting in cardiac arrest, irreversible brain damage, and death. Stent dislodgement and embolization into the iliac artery occurred in 1 patient. The stent was successfully secured and followed by placement of a second stent at the target location. The procedure was uncomplicated in 4 patients, who remain alive after a mean follow-up of 10 ± 2.6 months. Intravenous vasodilator therapy was weaned uneventfully after TPS in 3 patients. Conclusions TPS creation in children is feasible and results in hemodynamic improvement. Further insights into high-risk markers, such as reduced preprocedural LV function and preload reserves, are important for guiding patient selection.

To investigate numerous endoscopic techniques that have been described for the treatment of benign prostate enlargement. Plasma-button enucleation of the prostate (B-TUEP) is a successful treatment option because the large surface creates a fast enucleation process, vaporization, and concomitant hemostasis. The aim of this study was to evaluate the efficacy of bipolar button electrode transurethral adenoma enucleation (B-TUEP) in saline solution. The second end point was to determine the change of International Prostate Symptom Score (IPSS), post-void residual urine, International Index of Erectile Function, transrectal ultrasound gland volume evaluation, and prostate-specific antigen.Between July 2011 and March 2012, 50 consecutive patients underwent B-TUEP in our facility, all performed by a single surgeon (R.G.). All patients were preoperatively assessed with maximum urinary flow rate, single-question quality of life assessment, IPSS and the International Index of Erectile Function questionnaires, transrectal ultrasound gland volume evaluation, prostate-specific antigen, and post-void residual urine.We observed a significant improvement at 12, 24, and 36 months in terms of maximum urinary flow rate (22.3 ± 4.74 mL/s, 23.2 ± 0.30 mL/s, and 23.6 ± 1.26 mL/s, respectively, P .01) and quality of life (5.28 ± 0.97, 5.69 ± 0.90, and 5.73 ± 0.87). IPSS and IEEF scores improved significantly (P .05). Gland volume evaluation and post-void residue decreased (P .001). The prostate-specific postoperative antigen levels were 0.76 ± 0.61 ng/mL, 0.7 ± 0.51 ng/mL, and 0.62 ± 0.18 ng/mL, at 12, 24, and 36 months, respectively. Two patients (4%) had persistent bladder outlet obstruction requiring reoperation.After 3-year follow-up, B-TUEP represents an effective, durable, and safe form of surgical intervention. B-TUEP is an alternative treatment for symptomatic benign prostate enlargement.

We describe the case of a boy with spondyloepiphyseal dysplasia congenita. At birth, he experienced severe respiratory distress necessitating tracheotomy. Endoscopy done because mechanical ventilation failed to resolve desaturations disclosed severe tracheo-bronchomalacia. A Polyflex silicone stent was placed in the trachea (replaced by Y-Dumon stent) and 2 Palmaz metallic stents in the mainstem bronchi (overlapped with 2 Jomed stents 5 years later). Airway stenting guaranteed a suitable respiratory status and allowed a child who was expected to die at birth, to reach 13.5 years old in good conditions.

Gastric mucosal injury is frequently observed in nonclinical studies of nonhuman primates. Because microscopic evaluation of stomach is generally a terminal procedure, our objective was to determine whether serum pepsinogen I (PG I) could serve as a noninvasive biomarker for detection of gastric mucosal injury in monkey. Serum PG I was measured using a commercial human immunoassay in cynomolgus monkeys ( n = 166) prior to dosing and/or terminally in 11 studies of up to 1 month duration. Mean ( SD) PG I values (ug/L) for monkeys with ( n = 59) and without ( n = 100) gastric mucosal degeneration were 101 (215) and 28 (12.6), respectively. For monkeys with baseline and terminal PG I data, mean ( SD) fold change (ratio of terminal to baseline PG I) for monkeys with ( n = 57) and without ( n = 76) glandular degeneration were 4.1 (11.3) and 1 (0.28). Receiver operating characteristic area under the curve (AUC) data demonstrated moderate diagnostic accuracy for serum PG I for glandular degeneration, AUC ( SE) 0.789 (0.04), with improved diagnostic accuracy as a fold change of baseline, AUC ( SE) 0.816 (0.04), consistent with the large interindividual but low intraindividual variability of serum PG I values in control monkeys. These data demonstrate that serum PG I is a useful biomarker of drug-induced gastric mucosal injury in the cynomolgus monkey.

Background Pre-clinical and clinical evidence suggests a rationale for the use of anti-angiogenic agents, including sorafenib, in recurrent and/or metastatic salivary gland carcinomas (RMSGCs). This study evaluates the activity of sorafenib in patients with RMSGCs and also investigates whether the activity of sorafenib could be related to its main tailored targets (i.e. BRAF, vascular endothelial growth factor receptor 2 [VEGFR2], platelet-derived growth factor receptor α [PDGFRα] and β, RET, KIT). Patients and methods Patients received sorafenib at 400 mg BID. The primary end-point was response rate (RR) including complete response or partial response (PR); secondary end-points included RR according to Choi criteria, disease control rate (DCR), overall survival (OS), and progression-free survival (PFS). Results Thirty-seven patients (19 adenoid cystic cancers, ACC) were enrolled. Six PRs were recorded. RR was 16% (95% confidence interval [CI]: 6–32; 11% in ACC and 22% in non-ACC). Choi criteria could be applied in 30 out of 37 cases with a RR of 50% (95% CI: 31–69%); DCR was 76% (95% CI: 59–88%). Incidence of ≥G3 adverse events was 29.7%. Median PFS and OS for the entire population were 5.9 months and 23.4 months, respectively. Median PFS and OS were 8.9 and 26.4 months for ACC versus 4.2 and 12.3 months for non-ACC patients. All the cases showed expression of PDGFRβ in the stroma and VEGFR2 in endothelial cells; PDGFRα positivity was found in the stroma of four (27%) cases. All except for two cases showed no PDGFRβ, VEGFR2 and PDGFRα expression in the tumour cells. KIT expression was restricted to ACC and a weak RET expression was limited to one adenocarcinoma, not otherwise specified (NOS). No BRAF mutation was found. No correlation was observed between the sorafenib activity and the expression of its markers although all six responders (two ACC, one adenocarcinoma, NOS, one salivary duct cancer [SDC], one high-grade mucoepidermoid [HG-MEC] and one poorly-differentiated cancer) are enriched in the stromal component showing a PDGFRβ immunodecoration. In ACCs, immunohistochemistry revealed MYB protein expression in 15/16 cases (94%) and the MYB-NFIB fusion oncogene was observed in 9/14 (64%). Conclusions Sorafenib is the first anti-angiogenic agent to demonstrate activity in RMSGC patients, particularly in some histotypes such as HG-MEC, SDC and adenocarcinoma, NOS. The PDGFRβ-positive rich stromal component characterising these histotypes and the lack of correlation between the activity of sorafenib and its targets suggests anti-angiogenic effect as the prevalent mechanism of action of sorafenib in SGCs.

Intraoperative pneumothorax during general anesthesia is a dangerous event. It is a possible cause of sudden intraoperative hypoxia, which can be critical especially in high-risk patients such as those with end-stage heart failure. Early diagnosis and effective treatment are essential. We describe the case of a pneumothorax during cardiac transplantation, diagnosed by ultrasound and immediately treated. A good skill in lung ultrasound is advantageous in the management of intraoperative hypoxia, particularly for prompt diagnosis of pneumothorax.

The aim of this study was to evaluate the in vivo effects at 3 years of preservative-free tafluprost on corneal health. It was a prospective, masked, study on consecutive patients with a new prescription of preservative-free (PF) tafluprost (naïve-N or switched-S, 44 and 14 patients), and preserved (P) bimatoprost 0.003% or travoprost 0.004% (P-group, 35 patients). A complete ophthalmic examination and an in vivo corneal confocal microscopy evaluation were performed at baseline and every 6 months for 3 years. Ninety-three patients were enrolled, clinical parameters were similar in the groups at baseline, apart from intraocular pressure (IOP) which was lower in the S-group (p = 0.012). Both at baseline and over time, confocal microscopy parameters had different trends. At baseline, keratocyte activation was similar in the three groups (p = 0.43) but over the next months naïve patients treated with PF-tafluprost presented a significant (p = 0.004) reduction in keratocyte activation. Sub-basal nerves tended to increase in patients switched to PF-tafluprost (p = 0.07) while were stable in the other two groups (p = 0.11 in PF and 0.40 in P group). Grade of tortuosity was stable over time in the three groups. Beading-like formations were stable over time for the P- and the PF-group, while significantly increased in the S-group (p = 0.027). Endothelial density values were statistically different at baseline (p = 0.007), they decreased both in PF-group and in S-group (p = 0.048 and 0.001, respectively), while increased in P-group (p = 0.006). Our study is the first to show that a PF-tafluprost formulation does not significantly alter the corneal structures as examined by confocal microscopy after 36 months of topical daily therapy, while improving corneal alterations due to chronic preserved therapies.

Background Left pulmonary artery (LPA) sling (PAS) is a vascular ring, which is frequently associated with long-segment tracheal stenosis (TS). Mortality rate in operated children is still high, especially in cases of severe tracheal hypoplasia and/or associated congenital heart defects (CHDs). We report our experience of treatment and follow-up in a pediatric cohort of patients affected by PAS with severe tracheobronchial involvement. Methods From 2005 to 2017, we enrolled 11 children diagnosed with PAS and congenital TS requiring surgical intervention. Echocardiography, computed tomography, and bronchoscopy were performed in all patients. Associated CHD were present in 5 (45%) patients. Tracheal reconstruction techniques included slide tracheoplasty (7/11; 63%), slide tracheoplasty and costal cartilage graft (2/11; 18%), and Hazekamp technique (2/11; 18%).Nine patients underwent LPA direct reimplantation and concomitant tracheoplasty; concomitant surgical repair for CHD was performed in three children. Results Over a mean follow-up of 30 months (range: 3–75 months), a late mortality of 18% was registered; no early death occurred. Good flow through LPA could be documented in all patients. Ten children required operative bronchoscopies (mean: 16/patients) aimed at stent positioning/removal, treatment of granulomas, and tracheobronchial dilatation. Conclusions Severe tracheobronchial stenosis and associated CHD were the main determinants for hospitalization time, intensive assistance, and repeated endoscopic procedures.Patients affected by PAS/TS complex require a careful management at high-specialized centers providing multidisciplinary team.Respiratory endoscopy may play a central role both in preoperatory assessment and in postoperative management of patients showing severe tracheobronchial involvement.

Echocardiography is the primary imaging method for the diagnosis and assessment of congenital heart disease in the pediatric and adult groups of patients. In the group of congenital septal defects, transthoracic echocardiography (TTE) is the primary modality to characterize the type of defect (atrial septal defect, ventricular septal defect, and atrioventricular septal defect) and to describe the echoanatomic and physiopathological features of a singular lesion that is generally involved in a shunt and the associated defects. Particularly in the adult patient with substandard echocardiographic precordial windows, transesophageal echocardiography (TEE) has permitted the acquisition of anatomic and hemodynamic information not obtainable by TTE. In this chapter, we accentuate the role of color Doppler echocardiography and contrast echocardiography for the accurate diagnosis of a septal defect; these techniques are useful also during reparation of defects, particularly by percutaneous closure: in this case use of 2-D TEE is mandatory, but today use of 3-D echocardiography and intracardiac echocardiography is growing. We underline that echocardiography is fundamental for intensivists because it permits primarily immediate diagnosis and clinical treatment of adult patients with a congenital septal defect and so it is possible to send these kinds of patients at an early stage to a center which routinely manages congenital heart diseases. Echocardiography plays an essential role in the diagnosis and management of congenital septal abnormalities because it has high sensitivity. As well as cardiologists, intensivists and anesthesiologists also are frequent users of it in their daily work.

Fatigue is one of the most distressing symptoms of cancer patients. Its characteristics and impact on quality of life have not been fully explored and treatment of cancer-related fatigue in Italian oncological centers has not been codified. A cross-sectional study was carried out on all patients attending for any reason the 24 participating centers in two non-consecutive days. Patients with fatigue filled out the Brief Fatigue Inventory (BFI) questionnaire and reported any pharmacological or non-pharmacological treatment for fatigue. From October 2014 to May 2015, 1394 cancer patients agreed to participate in the study. Fatigue was referred by 866 (62.1%) of patients; its duration was > 4 months in 441 patients (50.9%). In the investigators’ opinion, the most important (probable or almost sure) determinants of fatigue were reduced physical activity (271 patients), anxiety (149), pain (131), insomnia (125), anemia (123), and depression (123). Fatigue of moderate/severe intensity was reported by 43%/29.2% of patients, while usual fatigue in the last 24 h by 45%/33.1%, and the worst fatigue in the last 24 h by 33%/54.8%, respectively. Concerning the impact on quality of life, fatigue interfered moderately/severely with general activity in 30.8%/38.6% of patients, with mood in 26.1%/32.8%, with the ability to work in 27.9%/35.6%, with normal work in 26.7%/38.9%, with relationships with others in 21%/23.4% and with the ability to amuse themselves in 22.2%/33.1%. Only 117/866 patients (13.5%) received a pharmacological treatment represented by a corticosteroid in 101 patients (86.3%) while 188 patients (21.7%) received a non-pharmacological treatment such as physical exercise (120 patients, 63.8%) and various alimentary supplements (52 patients, 27.6%). Cancer-related fatigue is frequently reported by oncological patients; its intensity and impact on quality of life is relevant.

Simple Summary Small cell lung cancer (SCLC) remains the most aggressive form of neuroendocrine tumor of the lung, for which treatment options remain limited. The introduction of immune checkpoint inhibitors has modified for the first time the therapeutic strategies in patients with extensive disease after decades. New therapeutic approaches are required. Deeper knowledge of tumor biology is required to gain new insights into this complex disease. Abstract Several trials have tried for decades to improve the outcome of extensive disease small cell lung cancer (ED-SCLC) through attempts to modify the standard treatments. Nevertheless, platinum/etoposide combination and topotecan have remained respectively the first and the second line standard treatments for the last 40 years. With the advent of immunotherapy, this scenario has finally changed. Our review aims to provide an overview of the primary studies on the actual therapeutic strategies available for ED-SCLC patients, and to highlight emerging evidence supporting the use of immunotherapy in SCLC patients.

This study evaluates the effects of dietary supplementation of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) glycoside on the performance, tibia mineral concentrations, and inflammatory responses of broilers challenged with lipopolysaccharides (LPS). At 20 days old, 144 male broilers were weighed and distributed in a completely randomized design with three treatments, eight replicates, and six birds per experimental unit. The treatments were a basal diet without LPS administration (CON), a basal diet with LPS administration (CON + LPS), and a basal diet supplemented with 5 μg of 1,25(OH)2D3-glycoside/kg of diet with LPS administration (SUP + LPS). The LPS challenge was administered as intraperitoneal applications at 21 and 23 days of age (1 and 1.12 mg/kg of body weight, respectively). Four hours after the first LPS application, one bird per experimental unit was euthanized to collect blood, spleen, duodenum, and jejunum samples. We evaluated the broilers’ performance at 25 days of age, when all birds were slaughtered to analyze calcium and phosphorus levels in the tibia. We analyzed the data using a one-way ANOVA and compared the means with the Tukey test at 0.05 significance. The CON + LPS birds showed less weight gain (WG) than the CON and SUP + LPS groups (P = 0.019). The treatments had no effect on feed intake, feed conversion, serum levels of bone alkaline phosphatase, calcium, and phosphorus, or calcium and phosphorus in the tibia of birds (P > 0.05). The IL-10 level in the jejunum was higher (P = 0.011) in SUP+LPS birds than in the CON and CON+LPS groups. Among birds challenged with LPS, those supplemented with 1,25(OH)2D3-glycoside showed greater mRNA expression of IL-10 (P = 0.014) and IL-1β (P = 0.045) in the spleen; however, no effect was observed on the expression of these cytokines in the duodenum and jejunum of the birds (P > 0.05). In conclusion, dietary supplementation with 1,25(OH)2D3-glycoside preserves WG and modulates the inflammatory response by increasing the production of IL-10 in the jejunum and the mRNA expression of IL-10 and IL-1β in the spleens of broilers challenged with LPS, although bone mineralization is unaffected.

OBJECTIVES: We describe the way we treated 7 children with critical long-term complications after metallic balloon-expandable stenting in the left mainstem bronchus. METHODS: Endoscopic follow-up included a first bronchoscopy 3 weeks after stenting, then monthly for 3 months, every 4-6 months up to 1 year and at scheduled times to calibrate stent diameter up to final calibration. When major complications occurred, patients underwent chest computed tomographic angiography. RESULTS: In 1 of the 7 children (median age 2.8 years), metallic left bronchial stenting served as a bridge to surgery. After a median 4-year follow-up, all 7 children experienced recurrent stent ovalizations with stent breakage in 3 and erosion in 1. In 4 children, computed tomographic angiography showed abundant peribronchial fibrous tissue, in 2 left mediastinal rotation and in 1 displacement along the left bronchus after pulmonary re-expansion as the cause of stent-related complication. Of the 7 children, 6 underwent surgery (5 posterior aortopexy and 1 section of the ligamentum arteriosus) and 3 required nitinol stents placement within the metallic ones. One patient completed the follow-up, and 1 patient was lost to follow-up. All 5 remaining children still have permanent bronchial stents in place, patent and re-epithelialized after a median 10.5-year follow-up. There were no deaths. CONCLUSIONS: Satisfactory anatomical relationships when children have stents placed in the left mainstem bronchus alone do not guarantee the final success. Several mechanisms intervene to cause critical stent-related complications in children during growth. Permanent metallic stents should be used carefully, and only in selected patients.

Background Gram-negative bacteremia (GNB) is a major cause of illness and death after hematopoietic stem cell transplantation (HSCT), and updated epidemiological investigation is advisable. Methods We prospectively evaluated the epidemiology of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods. we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant. Results The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis, variables associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA-mismatched donor and from cord blood, older age, and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant pathogen was significantly associated with an increased risk of posttransplant infection by the same microorganism in allo-HSCT. Colonization by resistant gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4 months both in allo-HSCT (hazard ratio, 2.13; 95% confidence interval, 1.45–3.13; P Conclusions Pre-engraftment GNB is an independent factor associated with increased mortality rate at 4 months after auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB. Clinical Trials registration NCT02088840.

Background Oral mucositis (OM)-related pain affects most patients with head and neck cancer during treatments, but its management is not standardized. Methods We retrospectively collected data about the opioid therapy used for OM-induced pain in all patients with oropharyngeal cancer treated with chemoradiotherapy (CRT) between 2009 and 2013. To compare the different opioids, a conversion into oral morphine equivalent daily dose (OMEDD) was performed. The highest OMEDD (h-OMEDD) and the opioids' weekly increase were associated with patient, tumor, or treatment-related characteristics in order to identify predictive factors of opioid consumption. Results Ninety-seven percent of patients received opioids. The h-OMEDD was significantly correlated with a higher OM-grade and a lower smoking history. The weekly opioids' increase was higher in patients with lower smoking history and human papillomavirus (HPV) positivity. Conclusion Opioid therapy remains the mainstay for OM-related pain management during CRT. The role of previous smoking and HPV on opioid use needs further confirmations. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

6553 Background: Emerging data suggest that radiomics can be used to predict outcomes in SCCHN. At present, only few data are available for pre-treatment MRI. Methods: Study population was retrieved from an ongoing multicenter, randomized, prospective trial (NCT02262221, HETeCo) evaluating health and economic outcomes of two different follow-up (FUP) strategies (intensive vs non-intensive) in effectively cured stage III-IV (VIII TNM ed.) SCCHN. We selected only patients with both pre- and post-contrast enhancement T1 and T2-weighted baseline MRI (b-MRI) and at least 2 years (2y) of FUP. A radiomic model was developed to identify high risk (HR) and low risk (LR) of disease recurrence. Radiomic features (RF) were extracted from the primary tumor in the b-MRI. The best RF combination was selected by Least Absolute Shrinkage and Selection Operator (LASSO). Ten-fold cross-validation was used to compute sensitivity, specificity and area under the curve (AUC) of the classifier. Kaplan-Meier (KM) curves were estimated for HR and LR, for both overall survival (OS) and disease-free survival (DFS) and log rank test was performed. Three years (3y)-DFS and OS were also estimated for the two groups. The radiomic risk class was used as a new variable in a multivariate Cox model including well established prognostic factors in SCCHN (TNM stage, subsite and HPV). Results: Out of 155 enrolled HETeCO patients, 98 baseline imaging were retrieved of which 57 b-MRI. Of these, 51 met the eligibility criteria (25 in intensive and 26 in non-intensive arm). Baseline patients’ characteristics were: median age 66 yr (38-86); sex (M 42; F 9); median smoking history: 30 packs/y (1-100); 25 oral cavity (49%), 18 oropharynx (35%, 14 HPV+), 6 larynx (12%), 2 hypopharynx (4%). At a median FUP of 42 months (25-64), 45 (88%) patients are still alive. The recurrence rate was 20% (10/51, of which 2 distant). In total, 1608 RF were extracted. The sensitivity, specificity and AUC of the classifier were 90%, 76%, and 80%, respectively. The radiomic risk class was found to be an independent prognostic factor for both DFS and OS (p=0.01 and p=0.046, respectively). KM curves for DFS and OS were significantly different between HR and LR groups (p=0.002 and p=0.04, respectively). In HR vs LR, 3-y DFS and OS were: 78% [61-100%] vs 97% [90-100%], and 88% [75-100%] vs 96% [88-100%], respectively. Conclusions: Radiomics of pre-treatment MRI can predict outcomes in SCCHN. External validation of this preliminary radiomics-based model is currently ongoing.

Infective endocarditis (IE) rarely causes ACS from septic emboli. When this occurs, the mortality rate is very high. We present a case of STEMI secondary to IE. A 77-year-old male with hypertension and dyslipidemia presented with presyncope. ECG initially revealed normal sinus rhythm without acute

Background: Head and neck cancer (HNC) patients can experience symptoms due to the tumor itself or to the treatment, with an impact on health-related quality of life (HRQoL). Patient-reported outcome (PRO) measures pertaining to HRQoL are used in medical research and to support clinical decisions. PRO instrument applicability and cultural adaptation must be tested for each population. The aim of this study is to linguistically validate the Italian translation of the M.D. Anderson Symptom Inventory—Head and Neck Module (MDASI-HN). Methods: Following forward and backward translation of the items of the English MDASI-HN into Italian, it was administered along with a cognitive debriefing to HNC patients able to read and understand Italian language. Individual and group responses are presented using descriptive statistics. Results: From May 2013 through September 2013, 56 patients with HNC (18 during curative treatment, 20 in palliative chemotherapy, and 18 in follow-up period) completed the MDASI-HN followed by accompanying cognitive debriefing. Ninety-nine percent of the individual MDASI-HN items were completed. Average time to complete the MDASI-HN was 8.5min (range 3–15). Results suggested overall ease of completion, relevance, and comprehensibleness of this translated self-report instrument in this Italian patient population. Conclusions: The Italian version of the MDASI-HN is linguistically valid; future research should explore dimensionality, reliability, and convergent, discriminant, and predictive validity of this patient-reported instrument, in order to use this translated version in outcomes research and clinical settings.

Background Urotensin II receptor has been poorly studied in prostate cancer. To evaluate the expression of urotensin II receptor (UII-R) in patients undergoing radical prostatectomy. Methods Overall, we identified 140 patients treated with retropubic radical prostatectomy (RP) in one center. UII-R was evaluated in prostate biopsies with immunohistochemical staining, resulting in a granular cytoplasmic positivity, through automated system using the kit Urotensin II Receptor Detection System provided by Pharmabullet srl. Immunostained slides were independently and blindly evaluated by ten uro-pathologists. To evaluate UTII-R expression three different parameters were considered: localization, granules dimensions and intensity of expression. A score from 0 to 3 was applied to each parameter to obtain a score from 0 to 9. Each parameter and the total score were evaluated as predictors of high grade disease on surgical pathology and of advanced stage disease. Accuracy of total score for the prediction of upgrading and upstaging was analyzed using receiver operator characteristics curve and decision curve analysis (DCA). Results On radical prostatectomy 92/140 (66%) presented high grade disease on surgical pathology. Patients with high grade disease presented an apical distribution of the receptor, larger granules and a more intense expression when compared to patients with low grade disease. A well they presented a higher total score. Subscores and total scores were found to be predictors of upgrading and upstaging. On ROC analysis total score presented an AUC of 0.72 and 0.70, respectively, for the prediction of upgrading and upstaging. On DCA total score showed a clinical benefit in the prediction of adverse pathological outcomes. Conclusion Urotensin II receptor is a potential marker of adverse pathological outcomes. Further studies should confirm our data and evaluate its role as a prognostic marker.

The aim of this cross-sectional study is to evaluate the factors associated with patient-reported dysphagia in patients affected by locally advanced oropharyngeal cancer (OPC) treated with definitive intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy (CHT), with or without induction CHT. We evaluated 148 OPC patients treated with IMRT and concurrent CHT, without evidence of disease and who had completed their treatment since at least 6 months. At their planned follow-up visit, patients underwent clinical evaluation and completed the M.D. Anderson dysphagia inventory (MDADI) questionnaire. The association between questionnaire composite score (MDADI-CS) and different patients' and tumor's characteristics and treatments (covariates) was investigated by univariable and multivariable analyses, the latter including only covariates significant at univariable analysis. With a median time from treatment end of 30 months [range 6-74 months, interquartile range (IQR) 16-50 months], the median (IQR) MDADI-CS was 72 (63-84). The majority of patients (82.4%) had a MDADI-CS ≥ 60. At multivariable analysis, female gender, human papilloma virus (HPV)-negative status, and moderate and severe clinician-rated xerostomia were significantly associated with lower MDADI-CS. Patient-perceived dysphagia was satisfactory or acceptable in the majority of patients. HPV status and xerostomia were confirmed as important predictive factors for swallowing dysfunction after radiochemotherapy. Data regarding female gender are new and deserve further investigation.