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Purpose To investigate prevalence and predictors of renal function variation in a multicenter cohort treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Methods Patients from 17 tertiary centers were included. Renal function variation was evaluated at postoperative day (POD)—1, 6 and 12 months. Timepoints differences were Δ1 = POD-1 eGFR − baseline eGFR; Δ2 = 6 months eGFR − POD-1 eGFR; Δ3 = 12 months eGFR − 6 months eGFR. We defined POD-1 acute kidney injury (AKI) as an increase in serum creatinine by ≥ 0.3 mg/dl or a 1.5 1.9-fold from baseline. Additionally, a cutoff of 60 ml/min in eGFR was considered to define renal function decline at 6 and 12 months. Logistic regression (LR) and linear mixed (LM) models were used to evaluate the association between clinical factors and eGFR decline and their interaction with follow-up. Results A total of 576 were included, of these 409(71.0%) and 403(70.0%) had an eGFR p p = 0.003), POD-1 AKI (OR 2.88, p p p p = 0.007), POD-1 AKI (OR 1.83, p = 0.02), and preoperative eGFR p p = 0.019), hydronephrosis (p p p = 0.001) influenced renal function variation (ß 9.2 ± 0.7, p Conclusion Age, preoperative eGFR and POD-1 AKI are independent predictors of 6 and 12 months renal function decline after RNU for UTUC.

The study's aim was two-fold: to describe the trend of hip subluxation in the largest sample of Italian nonambulatory cerebral palsy (CP) children ever published; to investigate its determinants. This single-centre retrospective cohort study included patients with spastic or dyskinetic CP, Gross Motor Function Classification System (GMFCS) level IV or V, age 0-18 years, having been referred to our unit before March 2020. The hip subluxation was measured by means of the migration percentage (MP). Other data were gathered such as sex, CP subtype, GMFCS level, presence of drug-resistant epilepsy, age, use of walkers with weight relief or standing devices, previous botulinum injection or hip surgery, oral or intrathecal baclofen and hip pain. Multiple linear stepwise regression was performed and descriptive statistics are provided. Spastic CP had MP maximum increase in early ages, with GMFCS level V values persistently higher than level IV. The dyskinetic subtype showed a slower increase of the MP, with GMFCS level IV presenting similar or higher values, compared to level V. Age, CP severity and spastic subtype are the main determinants. The stepwise multiple regression analysis demonstrated that weight relief walking and standing assistive devices, combined with botulinum contributed to reduce the MP progression. Dyskinetic CP showed overall lower MP values and a more variable behaviour relative to age and GMFCS level, compared to the spastic subtype. Standing and walking assistive devices, with partial or total weight relief, combined with individually targeted botulinum injections, should be considered in the management of bilateral nonambulatory CP patients, to prevent hip subluxation or its recurrence after surgery.

Several publications show that superselective conventional TransArterial ChemoEmbolization (cTACE), meaning cTACE performed selectively with a microcatheter positioned as close as possible to the tumor, improves outcomes, maximizing the anti-tumoral effect and minimizing the collateral damages of the surrounding liver parenchyma. Recent recommendations coming from the European Association for the Study of the Liver (EASL) and European Society of Medical Oncology (ESMO) highlighted that TACE must be used in Hepatocellular Carcinoma (HCC) “selectively targetable” and “accessible to supraselective catheterization.” The goal of the manuscript is to better define such population and to standardize superselective cTACE (ss-cTACE) technique. An expert panel with extensive clinical-procedural experience in TACE, have come together in a virtual meeting to generate recommendations and express their consensus. Experts recommend that anytime cTACE is proposed, it should be ss-cTACE, preferably with a 1.5–2.0 Fr microcatheter. Ideally, ss-cTACE should be proposed to patients with less than five lesions and a maximum number of two segments involved, with largest tumor smaller than 5 cm. Angio Cone-Beam Computed Tomography (CBCT) should be used to detect enhancing tumors, tumor feeders and guide tumor targeting. Whole tumor volume should be covered to obtain the best response. Adding peritumoral margins is encouraged but not mandatory. The treatment should involve a water-in-oil emulsion, whose quality is assessable with the “drop test.” Additional particulate embolization should be systematically performed, as per definition of cTACE procedure. Non-contrast CBCT or Multi-Detector Computed Tomography (MDCT) combined with angiography has been considered the gold standard for imaging during TACE, and should be used to assess tumor coverage during the procedure. Experts convene that superselectivity decreases incidence of adverse effects and improves tolerance. Experts recommend contrast-enhanced Computed Tomography (CT) as initial imaging on first follow-up after ss-cTACE, and Magnetic Resonance Imaging (MRI) if remaining tumor viability cannot be confidently assessed on CT. If no response is obtained after two ss-cTACE sessions within six months, patient must be considered unsuitable for TACE and proposed for alternative therapy. Patients are best served by multidisciplinary decision-making, and Interventional Radiologists should take an active role in patient selection, treatment allocation, and post-procedural care.

Colorectal cancer (CRC) incidence and mortality seems to be lower in women than in men. The present study aims to evaluate the impact of gender on CRC diagnosis, treatment, and survival. This is a retrospective cohort study based on a single-center dataset of CRC patients from the University Hospital of Trieste (Italy). Data of 1796 consecutive CRC patients referred to our center from November 11th, 2004, to December 31st, 2017, were analyzed. Right-sided carcinomas are more frequent in women than in men; furthermore, women had a lower surgical complication rate. Men showed a higher 5- and 10-year mortality. This survival benefit for women was observed independently of the tumor localization. The 5-year hazard ratio (HR) for women vs men was 0.776 (p 0.003), and after 10-year 0.816 (p 0.017). Regarding the disease-free survival (DFS), 5 and 10-year HR was 0.759 (p 0.034) and 0.788 (p 0.07), respectively. On multivariable analysis, respecting tumor localization, the odds of female gender were higher than man with right colon disease. Male gender was more independently associated with age at the surgery time. Women survival advantage was higher than men, except for patients older than 80. Surgical outcome and survival after CRC surgical treatment seem to be gender related. For this reason, gender could play an important role in CRC diagnosis and therapy, allowing an earlier diagnosis in women.

Purpose To retrospectively evaluate a cohort of athletically active patients who underwent surgery for adolescent idiopathic scoliosis (AIS), and to determine which clinical, surgical and anthropometric variables influenced their return to sport after surgery. Methods 112 adolescents who underwent high-density posterior fusion for AIS by a single surgeon were analyzed for clinical, surgical and demographic predictors of return to presurgical physical activity levels. Data were retrospectively collected by charts and X-rays analysis and patients interviews. Results Preoperative main curve Cobb was 64.4 ± 14.12° and obtained correction was 70.0 ± 12.5%. Included patients played many different sports (Table 4), most of all ballet (44/112, 39.2%), swimming (40/112, 35.7%) and gymnastics (32/112, 28.6%). At an average of 50.3 months follow-up, 76 (67.8%) patients returned to sports (RTS) at an equal or higher level than preoperatively. Younger age, lower Lenke curve type and lower main curve Cobb were significantly associated with RTS. As for RTS timing, patients who returned within the first 6 months were younger, with a higher Lenke and a less severe main curve, a more distal UIV and a more proximal LIV. No complications related to RTS were registered. Conclusion In conclusion, patients with adolescent idiopathic scoliosis safely returned to physical activity after surgery. Younger age, higher Lenke type and lower main curve severity predicted a quicker return to sport. However, prospective studies are needed to confirm these findings.

Objective: To disclose the nature of cognitive deficits in a cohort of patients with idiopathic autonomic failure (IAF) by exploring the relation among cognitive functions, cardiovascular autonomic failure (AF) and clinical progression to another α-synucleinopathy (phenoconversion). Methods: We retrospectively identified all patients with a clinical diagnosis of IAF who underwent a comprehensive neuropsychological evaluation, clinical examination and cardiovascular autonomic tests from the IAF-BO cohort. Brain magnetic resonance imaging (MRI) studies and cerebrospinal fluid (CSF) analysis, including neurofilament light chain (NfL), Alzheimer disease core biomarkers, and α-synuclein seeding activity were further evaluated when available. Correlations among cognitive functions, clinical features, cardiovascular AF, cerebral white matter hyperintensities (WMH) load, and CSF biomarkers were estimated using Spearman correlation coefficient. Results: Thirteen out of 30 (43%) patients with IAF displayed cognitive deficits (CI) mainly concerning executive functioning. Seven out of 30 (23%) met the criteria for mild cognitive impairment (MCI). The diagnosis of CI and MCI was not associated with phenoconversion or autonomic function parameters, including duration and severity of neurogenic orthostatic hypotension, presence and severity of supine hypertension, and nocturnal dipper profile. Twenty patients underwent a brain MRI and CSF analysis. MCI was related to WMH load (r = 0.549) and NfL levels (r = 0.656), while autonomic function parameters were not associated with either WMH or NfL levels. Interpretation: Cardiovascular AF and phenoconversion, underlying the spreading of neurodegeneration to the central nervous system, were not independent drivers of cognitive dysfunction in IAF. We identified WMH load and NfL levels as potential biomarkers of the neural network disruption associated with cognitive impairment in patients with IAF.

Aims: To evaluate the role of bisoprolol to control symptoms and left ventricular outflow tract obstruction (LVOTO) in a consecutive cohort of adults with hypertrophic cardiomyopathy (HCM). Methods and results: In this retrospective study, patients with HCM with an LVOT gradient ≥50 mmHg after Valsalva manoeuvre and New York Heart Association (NYHA) class II-III symptoms were assigned to receive bisoprolol (starting at 1.25 mg daily). The initial dose was increased every two weeks to achieve the target in LVOT gradient

Purpose The definition of chronic adult hydrocephalus encompasses different pathological entities with overlapping characteristics, including long-standing overt ventriculomegaly in adults (LOVA), late-onset idiopathic aqueductal stenosis (LIAS) and idiopathic normal pressure hydrocephalus (iNPH). The aim of our study was to identify preoperative clinical and radiological features peculiar of these diseases providing some pathophysiology inferences on these forms of hydrocephalus. Methods Clinical and radiological preoperative records, type of surgical treatment and clinical outcome of patients with chronic adult hydrocephalus who were surgically treated between 2013 and 2019 were retrospectively reviewed. Univariate and multivariate analyses were performed to evaluate the contribution of each variable to the differential diagnosis. Results In total, 105 patients were included: 18 with LOVA, 23 with LIAS and 64 with iNPH. On multivariate analysis, an enlarged cisterna magna and a more severe ventriculomegaly were associated with the diagnosis of LOVA, while an older age and DESH with iNPH. LIAS patients tend to have an higher prevalence of raised ICP symptoms. Based on that, a clinical and radiological scoring system was developed to distinguish between iNPH and no iNPH cases. A precise cut-off value with a sensitivity of 95.1% and a specificity of 90.6% was identified. Conclusions LOVA, LIAS and iNPH are different forms of chronic adulthood hydrocephalus and present different and peculiar clinical and radiological features, with an impact on the treatment and outcome prediction. The implementation of a clinical-radiological score for differential diagnosis may help the differentiation. Further studies are warranted.

BACKGROUND Dupilumab has been demonstrated to be an effective treatment for patients with moderate-to-severe atopic dermatitis (AD) in clinical trials. However, evidence of real-world experience with dupilumab in a broader population is limited to date. METHODS Adult patients with moderate-to-severe AD, defined as an Eczema Area Severity Index (EASI) score of 24 or higher, treated with dupilumab at ten Italian academic centers, were included in the study. Physician-reported outcome measures (EASI), patient-reported outcome measures (pruritus and sleep score, Dermatology Life Quality Index, DLQI) and serological markers [immunoglobulin (Ig) E and eosinophil count] after 16 weeks were analyzed. RESULTS We enrolled 543 patients with moderate-to-severe AD. Two patients (0.4%) discontinued treatment. The median ± interquartile percentage change from baseline to 16 weeks of treatment in the EASI score was -87.5±22.0 (p

Background Typical late gadolinium enhancement (LGE) patterns in dilated cardiomyopathy (DCM) include intramyocardial and subepicardial distribution. However, the ischemic pattern of LGE (subendocardial and transmural) has also been reported in DCM without coronar y arter y disease (CAD), but its correlates and prognostic significance are still not known. On these bases, this study sought to describe the prevalence and prognostic significance of the ischemic LGE pattern in DCM. Methods A total of 611 DCM patients with available cardiac magnetic resonance were retrospectively analyzed. A composite of all-cause-death, major ventricular arrhythmias (MVAs), heart transplantation (HTx) or ventricular assist device (VAD) implantation was the primary outcome of the study. Secondary outcomes were a composite of sudden cardiac death or MVAs and a composite of death for refractory heart failure, HTx or VAD implantation. Results Ischemic LGE was found in 7% of DCM patients without significant CAD or history of myocardial infarction, most commonly inferior/inferolateral/anterolateral. Compared to patients with non-ischemic LGE, those with ischemic LGE had higher prevalence of hypertension and atrial fibrillation or flutter. Ischemic LGE was associated with worse long-term outcomes compared to non-ischemic LGE (36% vs 23% risk of primary outcome events at 5 years respectively, P = .006), and remained an independent predictor of primary outcome after adjustment for clinically and statistically significant variables (adjusted hazard ratio 2.059 [1.055-4.015], P = .034 with respect to non-ischemic LGE). Conclusions The ischemic pattern of LGE is not uncommon among DCM patients without CAD and is independently associated with worse long-term outcomes. (Am Heart J 2022;246:117-124.)

The increasing use of ionizing radiation in healthcare is causing growing alarm about radiation protection of patients and the doses they receive during procedures. Radiation dose assessment for patients in radiodiagnostic procedures is the subject of interest in view of the recent Italian D.Lgs 31 July 2020, n. 101 (Decreto Legislativo 31 luglio 2020, n. 101) and one of its most important focuses is the prescription to provide patient exposure information as an integral part of the examination report. Dose monitoring systems are therefore essential for the collection of the dosimetric data. In order to analyse potential and critical issues of these software, different systems, adopted at the Antonio Cardarelli Hospital in Naples, were employed. Data extracted from the DoseWatch software (GE Healthcare) and Gray Detector (EL.CO. S.r.l. Healthcare Solutions, Italy) and relating to several protocols adopted for computed tomography (CT), were retrospectively analysed for the purpose of identifying critical issues in the data acquisition and recording phase, comparing with Italian nationwide diagnostic reference levels (DRLs), as provided for in regulatory provisions for radiation safety. Multiphase examinations were also included in this study. Once the distributions of volumetric CT Dose Index (CTDIvol) and dose-length product (DLP) were determined for each acquisition phase and total DLP (DLPtot) for each examination, the 25th, 50th and 75th percentiles were calculated for each distribution and then compared with the relevant Italian nationwide DRLs. In addition, to improve protocol optimization and dose reduction the magnitude of the CT acquisition settings chosen in each procedure was evaluated. In conclusion, these systems allow accurate analysis of radiation dose according to equipment and protocol over time. For the application of optimization measures, a constant use of the dose tracking software is required, which can be translated into actions on scan parameters and prospective data analysis.

Purpose: Robotic-assisted simple prostatectomy (RASP) is a novel surgical procedure for the management of obstructive symptoms caused by enlarged prostate glands. Before the introduction of minimally invasive techniques, the standard approach was the open simple prostatectomy (OSP). The aim of our study was to compare intraoperative and perioperative outcomes of robotic (RASP) and laparoscopic (LSP) simple prostatectomy. Methods: We retrospectively analyzed data from patients who underwent minimally invasive simple prostatectomy at the Urological Department of Portogruaro Hospital, Portogruaro, and at the Urological Department of “San Bassiano” Hospital, in Bassano del Grappa, from March 2015 to December 2020. Data collected from medical records included age, body mass index, prostate volume, operative time, preoperative International Prostatic Symptoms Score (IPSS), postoperative IPSS, time with drainage, blood transfusion, intraoperative complications, perioperative complications and length of hospital stay. Results: Robotic-assisted (n = 25) and laparoscopic simple prostatectomy (n = 25) were performed with a transvesical approach. No significant differences were observed regarding baseline characteristics, body mass index, prostate volume and IPSS. Operative time was lower in the laparoscopic group (122 min vs 139 min) (p = 0.024), while hospital stay was lower in the robotic group (4 days vs 6 days) (p = 0.047). Conclusions: Robotic-assisted simple prostatectomy is a safe technique with results comparable to laparoscopic simple prostatectomy, encompassing the advantage of a shorter hospitalization. Considering the costs and the limited availability of robotic-assisted simple prostatectomy, laparoscopic simple prostatectomy is a valid and safe alternative for experienced surgeons.

Objective: The aim of the study was to evaluate the accuracy of multiparametric Magnetic Resonance Imaging (mpMRI) in the detection of local recurrence of prostate cancer (PCa) with the evaluation of the added value of signal Intensity/Time (I/T) curves. Materials and methods: A retrospective analysis of 22 patients undergoing mpMRI from 2015 to 2020 was carried out, with the following inclusion criteria: performing transrectal ultrasound guided biopsy within 3 months in the case of positive or doubtful findings and undergoing biopsy and/or clinical follow-up for 24 months in the case of negative results. The images were reviewed, and the lesions were catalogued according to morphological, diffusion-weighted imaging (DWI) and dynamic contrast- enhanced (DCE) features. Results: The presence of local recurrence was detected in 11/22 patients (50%). Greater diameter, hyperintensity on DWI, positive contrast enhancement and type 2/3 signal I/T curves were more frequently observed in patients with local recurrence (all p < 0.05). Of all the sequences, DCE was the most accurate; however, the combination of DCE and DWI showed the best results, with a sensitivity of 100%, a specificity of 82%, a negative predictive value of 100% and a positive predictive value of 85%. Conclusions: The utility of MRI in the detection of local recurrence is tied to the multiparametric approach, with all sequences providing useful information. A combination of DCE and DWI is particularly effective. Moreover, specificity could be additionally improved using analysis of the signal I/T curves.

Background Hereditary transthyretin amyloidosis (ATTRv) is a rare, debilitating and fatal disease, mostly characterized by progressive axonal peripheral neuropathy. Diagnosis is still challenging and diagnostic delay in non-endemic area is about 3–4 years. The aim of this study was to arrange a clinical and electrophysiological score to select patients with axonal neuropathy that deserve screening for TTR mutation. Methods Thirty-five ATTRv patients and 55 patients with chronic idiopathic axonal polyneuropathy (CIAP) were retrospectively analyzed. Clinical and electrophysiological findings at first evaluation were collected. Based on significant results between the two groups, a compound (clinical and electrophysiological) score was arranged, and ROC analysis was performed to identify the ideal cut-off able to discriminate between the two groups. Results ATTRv patients presented a later age at onset, more frequent muscle weakness and carpal tunnel syndrome history. On the other hand, electrophysiological analysis showed that ATTRv patients had lower CMAP and SAP amplitude in all examined nerves. We arranged a compound score constituted by 7 total items, ranging from 0 to 12. ROC analysis showed an Area Under the Curve = 0.8655 and we set the cut-off ≥ 5 points to discriminate ATTRv patients with a sensitivity of 96.6% and a specificity of 63.6%. Conclusion Our study demonstrated that our compound score with cut-off ≥ 5 allows to discriminate ATTRv patients among subject affected by axonal polyneuropathy with a sensitivity > 95%. Thus, our compound score is a quick, easy and effective screening tool.

Most patients with ischemic colitis have a favourable evolution; nevertheless, the location in the right colon has been associated with a worse prognosis. The purpose of this study is to compare the clinical presentation and results of right colon ischemic colitis (CICD) with ischemic colitis of other colonic segments (non-CIDC).Retrospective, observational study of patients admitted to our hospital with ischemic colitis between 1993 and 2014, identified through a computerized search of ICD9 codes. They were divided into 2 groups: CICD and non-CICD. Comorbidities, clinical presentation, need for surgery, and mortality were compared. Multivariate analysis was performed using logistic regression adjusting for age and sex. Statistical significance was established at a value of P 0.05.A total of 204 patients were identified, 61 (30%) with CICD; 61% of CICD patients required surgery compared to 22% of non-CICD patients (P 0.001). Differences in post-surgical mortality (32% vs 55%) and overall mortality (20% vs 15%) were not statistically significant. CICD patients had more commonly unfavourable outcomes than non-CICD patients (61% vs 25%, P 0.001). The odds ratio (OR) for surgery was 5.28 and 4.47 for unfavourable outcomes for patients with CICD.CICD patients have a worse prognosis than non-CICD patients, 5 times more likely to need surgery and 4 times more likely to have unfavourable outcomes.

Although the use of specific MRI criteria has significantly increased the diagnostic accuracy of multiple sclerosis (MS), reaching a correct neuroradiological diagnosis remains a challenging task, and therefore the search for new imaging biomarkers is crucial. This study aims to evaluate the incidence of one of the emerging neuroradiological signs highly suggestive of MS, the central vein sign (CVS), using data from Fabry disease (FD) patients as an index of microvascular disorder that could mimic MS.In this retrospective study, after the application of inclusion and exclusion criteria, MRI scans of 36 FD patients and 73 relapsing-remitting (RR) MS patients were evaluated. Among the RRMS participants, 32 subjects with a disease duration inferior to 5 years (early MS) were also analyzed. For all subjects, a Fazekas score (FS) was recorded, excluding patients with FS = 0. Different neuroradiological signs, including CVS, were evaluated on FLAIR T2-weighted and spoiled gradient recalled echo sequences.Among all the recorded neuroradiological signs, the most striking difference was found for the CVS, with a detectable prevalence of 78.1% (57/73) in RRMS and of 71.4% (25/32) in early MS patients, while this sign was absent in FD (0/36).Our results confirm the high incidence of CVS in MS, also in the early phases of the disease, while it seems to be absent in conditions with a different etiology. These results corroborate the possible role of CVS as a useful neuroradiological sign highly suggestive of MS.• The search for new imaging biomarkers is crucial to achieve a correct neuroradiological diagnosis of MS. • The CVS shows an incidence superior to 70% in MS patients, even in the early phases of the disease, while it appears to be absent in FD. • These findings further corroborate the possible future central role of CVS in distinguishing between MS and its mimickers.

Background Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children Methods An observational retrospective study investigating the rate and the outcomes of off-label prescription of HAART was conducted on 225 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. Results 22.2% (50/225) of included children were receiving an off-label HAART regimen at last check. Only 26% (13/50) of off-label children had an undetectable viral load (VL) before the commencing of the regimen and the 52.0% (26/50) had a CD4 + T lymphocyte percentage > 25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13–5.19; p = 0.024). Moreover, children Conclusion The prescription of an off-label HAART regimen in perinatally HIV-1 infected children was common, in particular in children with detectable VL despite previous HAART and in younger children, especially those receiving their first regimen. Our data suggest similar proportions of virological and immunological successes at last check among children receiving off-label or on-label HAART. Larger studies are needed to better clarify efficacy and safety of off-label HAART regimens in children, in order to allow the enlargement of on-label prescription in children.

Background/Aim: Endometriosis is a gynecological estrogen-dependent inflammatory disease due to ectopic endometrial tissue and often associated with pelvic pain. Despite its high prevalence, there are still uncertainties about its pathogenesis, diagnosis, and therapy. Patients and Methods: This study presents a retrospective study conducted on 4,401 endometriosis patients, 584 of which underwent laparoscopic procedures. The archived data about clinical signs, magnetic resonance imaging (MRI) results, topography of the endometriosis lesions (obtained via laparoscopy) associated diseases, sample analysis and histological findings were analyzed. Next, the statistical associations between the information for each case, provided by these diagnostic tools were determined. Results: MRI is the most sensitive and specific diagnostic system for ovarian lesions, but poor in sensitivity and specificity for deep endometriosis lesions and not indicated for peritoneal lesions which remain the exclusive prerogative of laparoscopy. Clinical signs are essential for diagnosing deep lesions. The Ca125 and Ca19.9 markers have a poor reliability and their negativity in symptomatic patients has no clinical value, while in positive cases it could probably be used as a monitoring parameter. Conclusion: The results generated will help provide an accurate picture of the topography and distribution of endometriotic lesions. Correlation analyses between the data generated by the clinical-instrumental examinations and those on the site of the disease identified by laparoscopy, allow to define the predictive value of the clinical-instrumental signs in the diagnosis and localization of endometriotic disease.

Objectives: Here, we aim at describing the pattern of care, survival outcome and prognostic factors of ABC patients (pts) receiving third-line chemotherapy. Methods: Institutional registries across three academic medical centers were retrospectively reviewed. Kaplan–Meier estimators were used to calculate survival, the log-rank test to make comparisons, and the Cox proportional hazard models to assess the progostic impact of variables. Results: Among 101 pts included in the analysis. 68 (67.3%), 19 (18.8%) and 14 (13.8%) had intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer, respectively. Atotal of 63 (62.3%) pts received monochemotherapy, while 38 (37.6%) were treated with adoublet. The median OS and PFS were 5 and 3 months, respectively. Disease control rate was achieved in 23 (22.7%) pts, with 2 (2%) partial responses. Grade 3–4 treatment-related adverse events were reported in 22 (21.7%) pts. At multivariate analysis, ECOG PS (p

Background To detect the optimal timing of intervention based on different cervical vertebral maturation stage (CS1-2 vs. CS3-4) for the treatment of Class III malocclusion with early Class III protocol. Methods A total sample of 43 patients (23 females, 20 males) ranging between 7 and 13 years of age with dentoskeletal Class III malocclusion treated with the modified SEC III (Splints, Elastic and Chincup) protocol divided into two groups based on the cervical vertebral maturation stages (CS1-2 and CS3-4) was included in this retrospective observational longitudinal study. Patient compliance was assessed using a 2-point Likert scale. Statistical comparisons between the two groups were performed with independent sample t tests. Results No statistically significant differences for any of the cephalometric variables describing the baseline dentoskeletal features were found between the two groups except for the mandibular unit length that was significantly greater in the pubertal group (P = 0.005). The modified SEC III protocol produced favorable sagittal outcomes in both groups, whereas no statistically significant T1-T2 changes were found between the CS1-2 and CS3-4 groups for any of the angular and linear measurements. No significant differences were found in the prevalence rates of the degree of collaboration between the two groups (P = 1.000). Conclusions No significant differences between prepubertal and pubertal patients were found in the sagittal and vertical dentoskeletal changes with the modified SEC III protocol. Thus, this early Class III treatment produced similar favorable effects in growing subjects regardless of the cervical vertebral maturation stages from CS1 to CS4.

Thyroid nodules with indeterminate cytology represent 20% of all thyroid nodules. Inflammation plays an important role in cancer. Lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are independent prognostic scores in numerous cancers, although no study has documented their role in cytology indeterminate nodules. The aim of this study is to evaluate the role of LMR, NLR and PLR values as predictors of malignancy in patients with cytology indeterminate nodules.This retrospective study analysed data from 298 patients with indeterminate thyroid nodule. Anatomopathological and haematological data were analysed, dividing the population into two groups. LMR, NLR and PLR values were determined using ROC curve and data were analysed using independent samples t-test, test of proportions, Fisher's exact test and univariate and multivariate logistic regression.We found that a baseline LMR value ≥ 4.09 was indicative of benignity of indeterminate nodule. The probability of malignancy in patients with LMR4.09 was 26 times higher than patients with a LMR value ≥ 4.09.This study showed that only LMR has shown a concrete probability to find a thyroid cancer in patients with indeterminate nodules. Further studies are necessary to implement tailored treatment.Valutazione di LMR, NLR e PLR come predittori di malignità in noduli tiroidei indeterminati.I noduli tiroidei a citologia indeterminata rappresentano il 20% di tutti i noduli tiroidei. L’infiammazione gioca un ruolo importante nel cancro. LMR, NLR e PLR sono fattori prognostici indipendenti in numerosi tumori; tuttavia, nessuno studio ha mostrato il loro ruolo nei noduli a citologia indeterminata. Questo studio si propone di valutare il ruolo di LMR, NLR e PLR come predittori di malignità in pazienti con noduli a citologia indeterminata.Abbiamo analizzato retrospettivamente i dati di 298 pazienti con nodulo tiroideo indeterminato. Abbiamo analizzato i dati anatomopatologici ed ematologici, dividendo la popolazione in due gruppi. I valori cut-off di LMR, NLR e PLR sono stati determinati con la curva ROC e i dati sono stati esaminati utilizzando il t-test per campioni indipendenti, il test delle proporzioni, il Fisher exact test e la regressione univariata e multivariata.Un valore LMR basale ≥ 4,09 è indicativo di benignità. La probabilità di neoplasia nei pazienti con LMR4,09 è 26 volte superiore rispetto ai pazienti con valore LMR ≥ 4,09.Questo studio ha dimostrato che solo un valore di LMR4,09 ha una probabilità concreta che un nodulo a citologia indeterminata possa essere un cancro.

BACKGROUND & AIMS: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) has been shown to predict outcomes of patients with primary biliary cholangitis (PBC) in small-size studies. We aimed to validate the prognostic value of LSM in a large cohort study. METHODS: We performed an international, multicentre, retrospective follow-up study of 3,985 patients with PBC seen at 23 centres in 12 countries. Eligibility criteria included at least 1 reliable LSM by VCTE and a follow-up ≥ 1 year. Independent derivation (n = 2,740) and validation (n = 568) cohorts were built. The primary endpoint was time to poor clinical outcomes defined as liver-related complications, liver transplantation, or death. Hazard ratios (HRs) with CIs were determined using a time-dependent multivariable Cox regression analysis. RESULTS: LSM was independently associated with poor clinical outcomes in the derivation (5,324 LSMs, mean follow-up 5.0 ± 3.1 years) and validation (1,470 LSMs, mean follow-up 5.0 ± 2.8 years) cohorts: adjusted HRs (95% CI) per additional kPa were 1.040 (1.026-1.054) and 1.042 (1.029-1.056), respectively (p

Background: Gastro-bronchial and gastro-colic fistulas (GB-GC) represent a rare, but serious complication after laparoscopic sleeve gastrectomy (LSG). The aim of this study is to evaluate the efficacy of endoscopic first-line approach with endoscopic internal drainage (EID) by inserting double pigtail stents (DPS) Methods: We retrospectively analyzed data from 40 consecutive patients referred at two tertiary centers for gastro-bronchial (N=30) and gastrocolic (N=10) fistulas following LSG. Nineteen patients previously experienced emergency surgical drainage. The mean interval between the index surgery and endoscopic fistula treatment was 265.6±521 days. Results: Healing of the fistulous tract was achieved in 19 patients (47.5%), with complete resolution at an average follow-up of 16 months. Mean time of treatment duration was 157.8±141 days with 5.0±2.9 endoscopic sessions. No major adverse events were registered. Conclusions: Despite complete fistula healing was achieved in less than 50% of our population, EID for GB/GC fistula after LSG still represents the most conservative approach with low complications rate. Previous surgical drainage seems to be a positive prognostic factor for endoscopic healing. While the longer the interval between the index surgery and endoscopic treatment, the lower was the rate of treatment success. Graphical abstract: [Figure not available: see fulltext.]

Background: Adjuvant chemotherapy demonstrated a clear benefit in resected non-small cell lung cancer (NSCLC) with nodal disease (stages II-III), and a minimal benefit in tumors >4 cm (stage II, TNM 8th edition). Pleural invasion (PL), classified as visceral pleural invasion (VPI, which includes PL1 and PL2, and parietal pleural invasion (PL3), is an established negative prognostic factor. However, whether PL should influence the decisional algorithm of postoperative chemotherapy is controversial. Methods: A survival analysis of NSCLC patients who underwent radical surgery between 2010 and 2015 included in the SEER database was performed. Tumor stage and size, number of examined and positive nodes, histology, PL, and treatment data were extracted. Propensity score matching was performed. The benefit of chemotherapy was analyzed in two subgroups: standard of care (SOC), including patients with positive nodes or tumors ≥ 4 cm; non-SOC, including patients with tumors < 4 cm and negative nodes. Results: Records of 30,858 patients were extracted. 11,708 patients were included in the propensity score-matched analysis. In the SOC subgroup, including 8089 patients, all pleural invasion degrees were associated with progressively increased risk for death and shorter overall survival (OS), independently from chemotherapy administration. However, chemotherapy significantly improved the median OS regardless of the extent of PL. In the non-SOC subgroup, including 3619 patients, only PL3 was associated with increased mortality. The administration of chemotherapy did not improve survival outcomes. Conclusion: Chemotherapy should be strongly recommended in patients in the SOC-subgroup with pleural invasion. VPI is not associated with unfavorable prognosis in the non-SOC subgroup.

OBJECTIVE To investigate factors predicting the risk of developing 90-day postoperative complications and lymphatic-specific morbidity in patients undergoing surgical staging for high-risk endometrial cancer. METHODS This is a multi-institutional retrospective cohort study. Patients affected by apparent early-stage high-risk endometrial cancer (endometrioid FIGO grade 3 with deep myometrial invasion and non-endometrioid endometrial cancer) undergoing surgical staging between 2007 and 2019. Complications were graded according to the Clavien-Dindo classification system. Martin criteria were applied to improve quality of complications reporting. RESULTS Charts of 279 patients were evaluated. Lymphadenectomy, sentinel node mapping (SNM), and SNM followed by back-up lymphadenectomy were performed in 83 (29.7%), 50 (17.9%), and 146 (52.4%) patients, respectively. The former group of patients included 13 patients who had lymphadenectomy after the failure of the SNM technique. Thirteen (4.6%) patients developed severe postoperative events (grade 3 or worse). At multivariate analysis, body mass index (OR: 1.08 (95%CI: 1.01, 1.17)) and open abdominal surgery (OR: 2.27 (95%CI: 1.02, 5.32)) were the two independent factors predictive of surgery-related morbidity. Seven severe lymphatic complications occurred. The adoption of laparoscopic approach (p��

Introduction Irritable bowel syndrome is a common functional gastrointestinal disorder in children, characterized by recurrent abdominal pain associated with altered bowel habits in terms of both frequency and consistency. According to change in stool consistency it is categorized into 4 subtypes. From the etiological perspective, it is a multifactorial functional disorder with both central (psychosocial) and peripheral factors (altered bowel sensitivity, motility and microbiota) implied in the genesis of the symptoms. Several treatment options, addressing each underlying pathophysiological mechanism have been proposed. However, since in most cases a combination of factors takes part in symptoms' generation, the overall treatment response rate is often unsatisfactory if a multidisciplinary is not pursued. Areas covered The aim of this manuscript is to summarize the current pharmacotherapy in paediatric irritable bowel syndrome in order to aid clinicians in treating this challenging disorder. Expert opinion Most evidence involving paediatric populations rely on open label or retrospective studies and/or are not specifically designed for irritable bowel syndrome but tend to generalise their results to mixed populations of children with functional gastrointestinal disorders. A high placebo response rate combined with poor patients' selection could account for the overall weak evidence supporting the use of pharmacological agents in paediatric irritable bowel syndrome. Given the multifaceted nature of the disorder, multidisciplinary approaches combining pharmacotherapy with alternative treatments is highly recommendable.

Background Biological drugs have improved the management of immune-mediated inflammatory diseases (IMIDs) despite being associated with important safety issues such as immunogenicity, infections, and malignancies in real-world settings. Objective The aim of this study was to explore the potential of a large Italian multi-database distributed network for use in the postmarketing surveillance of biological drugs, including biosimilars, in patients with IMID. Methods A retrospective cohort study was conducted using 13 Italian regional claims databases during 2010–2019. A tailor-made R-based tool developed for distributed analysis of claims data using a study-specific common data model was customized for this study. We measured the yearly prevalence of biological drug users and the frequency of switches between originator and biosimilars for infliximab, etanercept, and adalimumab separately and stratified them by calendar year and region. We then calculated the cumulative number of users and person-years (PYs) of exposure to individual biological drugs approved for IMIDs. For a number of safety outcomes (e.g., severe acute respiratory syndrome coronavirus 2 [SARS-COV-2] infection), we conducted a sample power calculation to estimate the PYs of exposure required to investigate their association with individual biological drugs approved for IMIDs, considering different strengths of association. Results From a total underlying population of almost 50 million inhabitants from 13 Italian regions, we identified 143,602 (0.3%) biological drug users, with a cumulative exposure of 507,745 PYs during the entire follow-up. The mean age ± standard deviation of biological drug users was 49.3 ± 16.3, with a female-to-male ratio of 1.2. The age-adjusted yearly prevalence of biological drug users increased threefold from 0.7 per 1000 in 2010 to 2.1 per 1000 in 2019. Overall, we identified 40,996 users of biosimilars of tumor necrosis factor (TNF)-α inhibitors (i.e., etanercept, adalimumab, and infliximab) in the years 2015–2019. Of these, 46% (N = 18,845) switched at any time between originator and biosimilars or vice versa. To investigate a moderate association (incidence rate ratio 2) between biological drugs approved for IMIDs and safety events of interest, such as optic neuritis (lowest background incidence rate 10.4/100,000 PYs) or severe infection (highest background incidence rate 4312/100,000 PYs), a total of 43,311 PYs and 104 PYs of exposure to individual biological drugs, respectively, would be required. As such, using this network, of 15 individual biological drugs approved for IMIDs, the association with those adverse events could be investigated for four (27%) and 14 (93%), respectively. Conclusion The VALORE project multi-database network has access to data on more than 140,000 biological drug users (and > 0.5 million PYs) from 13 Italian regions during the years 2010–2019, which will be further expanded with the inclusion of data from other regions and more recent calendar years. Overall, the cumulated amount of person-time of exposure to biological drugs approved for IMIDs provides enough statistical power to investigate weak/moderate associations of almost all individual compounds and the most relevant safety outcomes. Moreover, this network may offer the opportunity to investigate the interchangeability of originator and biosimilars of several TNFα inhibitors in different therapeutic areas in real-world settings. Supplementary Information The online version contains supplementary material available at 10.1007/s40259-021-00498-3.

Background: Persistent type II endoleaks (ELIIp) occur in 8–23% of patients submitted to endovascular aneurysm repair (EVAR) and may lead to aneurysm progression and rupture. Intraoperative embolization of the abdominal aortic aneurysm (AAA) sac is effective to prevent their occurrence, however a method to achieve complete sac thrombosis has not been standardized yet. Aim of our study was to identify factors associated with prevention of ELIIp after intraoperative embolization, in order to optimize technical details. Methods: Patients at high risk for ELIIp, who underwent EVAR with AAA - sac coil embolization were prospectively collected into a dedicated database from January 2012 to March 2015. The endoluminal residual sac volume (ERV), not occupied by the endograft [ERV= AAA total volume (TV) – (AAA-thrombus volume (THV) + endograft volume (EgV)] was calculated on preoperative computed tomography and the concentration of coils implanted (CCoil= n coils implanted/ERV) for each patient was evaluated. AAA volumetric evaluation was conducted by dedicated vessels analysis software (3Mensio). ELIIp presence was evaluated by contrast-enhanced ultrasound at 6 and 12-month. Patients with ELIIp at 12 months (Group 1) were clustered and compared to patients without ELIIp (Group 2), in order to evaluate the incidence of ELIIp in patients undergone to preventive AAA-sac embolization, and identify the predictors of ELIIp prevention. Morphological potential risk factors for ELIIp such as TV, THV, VR% and EgV were also considered in all patients. Statistical correlation was assessed by Fisher Exact Test. Results: Among 326 patients undergone to standard EVAR, 61 (19% - M: 96.7%, median age: 72 [IQR: 8] years, median AAA diameter: 57 [IQR: 7] mm) were considered at high risk for ELIIp and were submitted to coil embolization. The median AAA total volume (TV) and median ERV were 156 (IQR: 59) cc and 46 (IQR: 26) cc, respectively. The median number and concentration of coils (IMWCE-38-16-45 Cook M-Ray) positioned in AAA-sac were 5 (IQR: 1) coils and 0.17 coil/cm3 (range 0.02-1.20). Among this high-risk population, the incidence of ELIIp was 29.5% and 23% at 6 and 12-month, respectively. Fourteen patients (23%) were clustered in Group1 and 47 (77%) in Group 2. Both groups were homogeneous for clinical characteristics and preoperative morphological risk factors. There were no differences in the preoperative median TV, AAA-thrombus volume (THV), %VR, EgV and number of implanted coils between Group1 and Group2. Patients in Group1 had a significantly higher ERV (59 [IQR: 13] cm3 vs. 42 [IQR: 27] cm3, P = 0.002) and lower CCoil (0.09 [IQR: 0.03] vs. 0.18 [IQR: 0.21], P = 0.006) than patients of Group2. ELIIp was significantly related to the presence of ERV > 49 cm3 (86 % vs. 42 %, Group1 and Group2 respectively, P = 0.006) and CCoil < 0.17coil/ cm3 (100% vs. 68%, Group1 e Group2 respectively, P = 0.014). Conclusion: According with our results, Coil concentration and endoluminal residual volume can affect the efficacy of the AAA – sac embolization in the prevention of ELIIp, moreover CCoil ≥0.17coil/ cm3 maight be considered to determine the tailored number of coils.

In 2010-2018 Northern Patagonia featured the longest severe drought of the last millennium. This extreme dry spell triggered widespread growth decline and forest dieback. Nonetheless, the roles played by the two major mechanisms driving dieback, hydraulic failure and carbon starvation, are still not clear and understudied in this seasonally dry region. Here, for the 1800-2017 period, we apply a retrospective analysis of radial growth, wood anatomical traits (lumen area, cell-wall thickness) and δ13 C and δ18 O stable isotopes to assess dieback causes of the iconic conifer Araucaria araucana. We selected three stands where declining (defoliated) and non-declining (not defoliated) trees coexisted along a precipitation gradient from the warm-dry Coastal Range to the cool-wet Andes. At all sites declining trees showed lower radial growth and lower theoretical hydraulic conductivity, suggesting a long-lasting process of hydraulic deterioration in their water transport system compared to non-declining, coexisting trees. Wood anatomical traits evidenced that this divergence between declining and non-declining trees started at least seven decades before canopy dieback. In the drier stands, declining trees showed higher water-use efficiency throughout the whole period, which we attributed to early stomatal closure, suggesting a greater carbon starvation risk consistent with thinner cell walls. In the wettest stand, we found the opposite pattern. Here, a reduction in water-use efficiency coupled with thicker cell walls suggested increased carbon assimilation rates and exposure to drought-induced hydraulic failure. The δ18 O values indicated different strategies of gas-exchange between sites which are likely a consequence of microsite conditions and water sources. Multi-proxy, retrospective quantifications of xylem anatomical traits and tree-ring isotopes provide a robust tool to identify and forecast which stands or trees will show dieback or, on the contrary, which will likely withstand and be more resilient to future hotter droughts.

Purpose: Data regarding vitamin D status in patients affected by gastroenteropancreatic (GEP) neuroendocrine tumor (NET) are limited and often showing contrasting results. The aim of the study was to evaluate the incidence of vitamin D deficiency (

Background: Acute Rheumatic Fever and Rheumatic Heart Disease are the leading cause of acquired heart disease in Low-Income Countries, and a common cause in High-Income Countries. We compared rheumatic carditis, its echocardiographic presentation at diagnosis and its progression in Italy and Rwanda. Methods: Retrospective study including all consecutive patients diagnosed with rheumatic carditis in an Italian (IT) and two Rwandan Hospitals (RW). Echocardiography was performed at diagnosis and three follow-up visits. Baseline characteristics, history of primary and secondary prophylaxis and cardiovascular complications data were collected. Results: Seventy-nine and 135 patients were enrolled in IT and RW, respectively. Mitral regurgitation was the most common lesion (IT: 70%, RW: 96%) in both cohorts; mixed valve lesions and severe lesions were more prevalent in RW. Age at diagnosis (IT: 8.4 ± 2.9 yrs.; RW: 11.1 ± 2.7 yrs.; P < 0.001), adherence to secondary prophylaxis (IT: 99%; RW: 48%; P < 0.001) and history of primary prophylaxis (IT: 65%; RW: 6%; P < 0.001) were different. During the follow-up, native valve lesions completely resolved in 38% of IT and in 2% of RW patients (P < 0.001). By contrast, cardiac surgery was performed in 31% of RW and 5% of IT patients (P < 0.001). Cardiovascular complications and death were only observed in RW. Conclusions: The more severe cardiac involvement, the higher rate of valve surgery, CV complications and deaths in RW, could be due to delayed diagnosis and treatment, scarce adherence to secondary prophylaxis and differences in social determinants of health.

Background: The cost-effectiveness of minimally invasive distal pancreatectomy (MIDP) is still a matter of debate. This study compares the cost-effectiveness of open (ODP), laparoscopic (LDP) and robotic distal pancreatectomy (RDP).Methods: Pubmed, Web of Science and Cochrane Library databases were searched. Studies comparing cost-effectiveness of ODP and MIDP were included.Results: A total of 1052 titles were screened and 16 articles were included in the study, 2431 patients in total. LDP resulted the most cost-efficient procedure, with a mean total cost of 14,682 +/- 5665 V and the lowest readmission rates. ODP had lower surgical procedure costs, 3867 +/- 768 V. RDP was the safest approach regarding hospital stay costs (5239 +/- 1741 V), length of hospital stay, morbidity, clinically relevant pancreatic fistula and reoperations.Conclusion: In this meta-analysis MIDP resulted as the most cost-effective approach. LDP seems to be protective against high costs, but RDP seems to be safer. (C) 2021 Elsevier Inc. All rights reserved.

Aims Although increasingly recognized as a distinct pathological entity, left bundle branch block‐induced cardiomyopathy (LBBB‐ICMP) is not included among the possible aetiologies of acquired dilated cardiomyopathies (DCM). While diagnostic criteria have been proposed, its recognition remains principally retrospective, in the presence of clinical and instrumental red flags. We aimed to assess the prevalence and clinical and instrumental features of LBBB‐ICMP in a large cohort of patients with DCM. Methods and results We analysed a cohort of 242 DCM patients from a two‐centre registry. Inclusion criteria were age > 18, non‐ischaemic or non‐valvular DCM, and LBBB on electrocardiogram. LBBB‐ICMP was defined according to previously proposed diagnostic criteria: (i) neither family history nor clinically identifiable potential causes for DCM; (ii) negative genetic testing; (iii) echocardiographic features including non‐severe chamber dilation, normal absolute and relative wall thickness, marked dyssynchrony, and normal right ventricular function; and (iv) absence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). From the entire cohort, we identified 30 subjects (similar in terms of New York Heart Association class I or II in 80% vs. 75%, P = 0.56; QRS width of 150 ± 22 vs. 151 ± 24 ms, P = 0.82; and cardiac remodelling of baseline end‐diastolic diameter 66 ± 8 vs. 65 ± 10 mm, P = 0.53) with a comprehensive dataset including CMR and genetic testing, required to verify the presence of the diagnostic criteria proposed for LBBB‐ICMP. The main characteristics of this subgroup were 73% males, age 45 ± 13 years, left ventricular ejection fraction (LVEF) 30 ± 10%, LGE in 38% of patients, and QRS complex of 150 ± 22 ms. Patients were under guideline‐directed medical therapy, and 57% of them were treated with cardiac resynchronization therapy (CRT). Two patients (6.67%, 50% males, age 53 ± 13 years) fulfilled the diagnostic criteria proposed for LBBB‐ICMP. After a follow‐up of 44 (12–76) months, LVEF was normal and QRS width significantly reduced (from 154 ± 25 to 116 ± 52 ms) in patients with LBBB‐ICMP. Both patients were under optimal medical treatment, and one was implanted with CRT‐D. Neither of the two patients experienced death, malignant ventricular arrhythmia, or heart failure hospitalization at follow‐up. Conclusions Left bundle branch block‐induced cardiomyopathy emerges as a distinct pathological entity, promptly identifiable in a minority but not negligible proportion of patients with newly diagnosed DCM and LBBB, using a series of diagnostic criteria including CMR and genetic testing. Further studies are needed to better elucidate the clinical course of LBBB‐ICMP.

The coronavirus disease 2019 (COVID-19) pandemic has led to lockdowns for much of the world. In Italy, all health procedures not directly related to COVID-19 were reduced or suspended, thus limiting patient access to hospitals. Any delay in cancer treatment presents the additional risk of tumors progressing from being curable to incurable. Specifically, melanoma survival rate strictly depends on tumor thickness, which, in turn, is a function of time. To estimate the impact on melanoma progression caused by the reduction in dermatologic services during the COVID-19 lockdown, a retrospective observational cohort study was conducted. This study was designed to compare the clinical and histologic characteristics of the primary melanomas removed in the first 2 months after the end of the lockdown (May-July 2020) in 12 Italian centers characterized by different COVID-19 case frequencies. The control group was represented by the melanomas removed during the same period in the previous 3 years. Overall, 1,124 melanomas were considered: 237 as part of the study group and 887 from the control group (average, 295), with a 20% reduction. Breslow thickness, as well as high-risk histotypes and melanomas with vertical growth, increased for all melanomas. Ulcerated and high mitotic index melanomas increased, particularly in northern Italy. In Italy, the lockdown led to a significant worsening of melanoma severity, causing a staging jump, with a consequent worsening of outcomes.

ImportanceDelays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis.ObjectiveTo evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer.Design, Setting, and ParticipantsThis retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery.ExposuresAny type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections.Main Outcomes and MeasuresThe primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable.ResultsA total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95% CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95% CI, 1.15-1.53; P P = .03).Conclusions and RelevanceThis cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients.

Background The diagnosis of periprocedural myocardial infarction (PMI) after coronary artery bypass graft (CABG) is based on biochemical markers along with clinical and instrumental findings. However, there is not a clear cutoff value of high-sensitivity cardiac troponin (hs-cTn) to identify PMI. We hypothesized that isolated hs-cTn concentrations in the first 24 h following CABG could predict cardiac adverse events (in-hospital death and PMI) and/or left ventricular ejection fraction (LVEF) decrease. Methods We retrospectively enrolled all consecutive adult patients undergoing CABG, alone or in association with other cardiac surgery procedures, over 1 year. Hs-cTn I concentrations (Access, Beckman Coulter) were serially measured in the post-operative period and analyzed according to post-operative outcomes. Results 300 patients were enrolled; 71.3% underwent CABG alone, 33.7% for acute coronary syndrome. Most patients showed hs-cTn I values superior to the limit required by the latest guidelines for the diagnosis of PMI. Five patients (1.7%) died, 8% developed a PMI, 10.6% showed a LVEF decrease ≥ 10%. Hs-cTn I concentrations did not significantly differ with respect to death and/or PMI whereas they were associated with LVEF decrease ≥ 10% (p value Conclusions Hs-cTn I at 9–12 h post-CABG may be useful to early identify patients at risk for LVEF decrease and to guide early investigation and management of possible post-operative complications.

The COVID-19 pandemic poses major challenges to healthcare systems. We aimed to investigate the impact of the pandemic on prescription and adherence patterns of chronic cardiovascular therapies (lipid-lowering [LL], oral antidiabetic drugs [AD], and antihypertensives [AH]) using administrative pharmaceutical databases. For each treatment, two cohorts of prevalent cases in 2019 and 2020 were compared. We evaluated the percentage change in dispensed packages and treatment adherence as a proportion of days covered (PDC). For all therapies, an increase was observed during March–April 2020 (LL: +4.52%; AD: +2.72%; AH: +1.09%), with a sharp decrease in May–June 2020 (LL: −8.40%; AD: −12.09%; AH: −10.54%) compared to 2019. The impact of the COVID-19 pandemic on chronic cardiovascular treatments appears negligible on adherence: 533,414 patients showed high adherence to LL (PDC ≥ 80%) in January–February 2020, and 2.29% became poorly adherent (PDC < 20%) in the following four-month period (vs. 1.98% in 2019). A similar increase was also observed for AH (1.25% with poor adherence in 2020 vs. 0.93% in 2019). For AD, the increase was restrained (1.55% with poor adherence in 2020 vs. 1.37% in 2019). The rush to supply drugs at the beginning of lockdown preserved the continuity of chronic cardiovascular therapies.

Our institution (University Hospital “L. Vanvitelli” - Naples, Italy) is a high-volume (HV) center in Naples metropolitan area and many patients are referred there to repeat thyroid fine-needle aspiration cytology (FNAC) after initial FNAC performed in low-volume institutions (LV). The aims of the study were to 1) examine the inter-observer agreement between HV and LV institutions according to the Italian thyroid cytology system, and 2) explore how the discordant FNAC reports were distributed in the European Thyroid Imaging and Reporting Data System (EU-TIRADS) categories. All consecutive cases of repeat FNAC performed at University Hospital “L. Vanvitelli” from January 2016 to December 2021 were retrospectively reviewed. Fleiss’ kappa (κ) was used to assess the inter-observer agreement, and categorical variables were compared by chi-square testing. P < 0.05 was considered statistically significant. A total of 124 nodules from 124 adults (mean age 49 years; mean maximum diameter 19 mm) were evaluated. Initial FNAC reports at LV were: 4 (3.2%) TIR1c, 64 (51.6%) TIR2, 48 (38.7%) TIR3A, 8 (6.5%) TIR3B, 0 TIR4, 0 TIR5. The overall FNAC reports were significantly different between the LV and HV institutions. At repeated FNAC, cytological diagnosis was unchanged in 64 (51.6%) cases including TIR2 and TIR3A results. A downgraded FNAC diagnosis (i.e., TIR2 vs TIR3A, TIR2 vs TIR3B) was observed in 36 (29%) nodules. An upgraded FNAC diagnosis (i.e., TIR3B vs TIR2, TIR3B vs TIR3A, TIR4 vs TIR3A, TIR5 vs TIR2, TIR5 vs TIR3B) was recorded in 24 (19.4%) nodules. The weighted inter-observer agreement between LV and HV institutions was poor (κ=0.133). Changed FNAC results were significantly (p=0.0023) more frequent in nodules at intermediate/high-risk (i.e., EU-TIRADS 4/5) than in those at no/low risk (EU-TIRADS 2/3) [i.e., 32/48 (66.7%) and 28/76 (36.8%), respectively]. Downgraded FNAC results were significantly more frequent in EU-TIRADS 2/3 (p=0.001) while upgraded FNAC were present only in EU-TIRADS 4/5 (24/24, 100.0%). The inter-observer agreement among LV and HV thyroid services was poor. The EU-TIRADS 4 and 5 categories included all the malignant nodules with FNAC results reclassified as higher risk (i.e., TIR3B-TIR4-TIR5) by the high-volume cytology service.

Aims Elevated maternal cholesterol during pregnancy (MCP) enhances atherogenesis in childhood, but its possible impact on acute myocardial infarction (AMI) in adults is unknown. Methods and results We retrospectively evaluated 310 patients who were admitted to hospital and whose MCP data were retrievable. Eighty-nine AMI patients with typical chest pain, transmural infarction Q-waves, elevated creatinine kinase, and 221 controls hospitalized for other reasons were identified. The AMI cohort was classified by MI severity (severe = involving three arteries, left ventricle ejection fraction ≤35, CK-peak >1200 mg/dL, or CK-MB >200 mg/dL). The association of MCP with AMI severity was tested by linear and multiple regression analysis that included conventional cardiovascular risk factors, gender, age, and treatment. Associations of MCP with body mass index (BMI) in patients were assessed by linear correlation. In the AMI cohort, MCP correlated with four measures of AMI severity: number of vessels (β = 0.382, P = 0.001), ejection fraction (β = −0.315, P = 0.003), CK (β = 0.260, P = 0.014), and CK-MB (β = 0.334, P = 0.001), as well as survival time (β = −0.252, P = 0.031). In multivariate analysis of patients stratified by AMI severity, MCP predicted AMI severity independently of age, gender, BMI, and CHD risk factors (odds ratio = 1.382, 95% confidence interval 1.046–1.825; P = 0.023). Survival was affected mainly by AMI severity. Conclusions Maternal cholesterol during pregnancy is associated with adult BMI, atherosclerosis-related risk, and severity of AMI.

Palliative radiotherapy (PRT) is known to be effective in relieving cancer related symptoms. However, many studies and clinical practice show several barriers hindering its use and worsening the quality of patient support during PRT. Various solutions were proposed to overcome these barriers: training on PRT for supportive and palliative care specialists and training on palliative care for radiation oncologists, and introduction of pathways and organizational models specifically dedicated to PRT. Evidence on innovative organizational models and mutual training experiences is few and sparse. Therefore, the aim of this literature review is to present a quick summary of the information available on improving the PRT quality through training, new pathways, and innovative organizational models. The majority of studies on the integration of PRT with other palliative and supportive therapies present low levels of evidence being mostly retrospective analyses. However, it should be emphasized that all reports uniformly showed advantages coming from the integration of PRT with supportive therapies. To actively participate in the integration of PRT and palliative care, providing comprehensive support to the needs of patients with advanced cancer, radiation oncologists should not only plan PRT but also: (i) assess and manage symptoms and stress, (ii) rapidly refer patients to specialists in management of more complex symptoms, and (iii) participate in multidisciplinary palliative care teams. To this end, improved education in palliative care both in residency schools and during professional life through continuous medical education is clearly needed. In particular, effective training is needed for radiotherapy residents to enable them to provide patients with comprehensive palliative care. Therefore, formal teaching of adequate duration, interactive teaching methods, attendance in palliative care services, and education in advanced palliative care should be planned in post-graduated schools of radiotherapy.

Purpose: We aimed to investigate the clinical performance of edoxaban for the treatment of pulmonary embolism (PE) in hospitalized COVID-19 patients. Methods: We conducted a retrospective analysis selecting hospitalized patients with COVID-19 admitted to our Institution from 20 May 2020 to 20 November 2020 with computer tomography (CT) detected PE at admission, treated with edoxaban after initial parenteral therapy. Clinical outcomes were compared between patients with and without ARDS at admission and between those with and without CT confirmed PE resolution. Results: 50 patients were included. Mean follow-up was 42.5±10days. No baseline differences were found between patients with ARDS (30%) and those without ARDS at admission. Patients with PE resolution (84%) were younger (P =0.03), had a shorter duration of fondaparinux therapy (9.9±3.8 vs 15.8±7.5days; P =0.0015) and length of hospitalization (36±8 vs 46±9days: P =0.0023) compared with those without PE resolution. 2 patients experienced major bleedings. At multivariate analysis the time to edoxaban switch was the only predictor of the PE resolution (HR: 0.92; 95% C.I. 0.86 to 0.99). Conclusion: Edoxaban was an effective and safe treatment for acute PE in COVID-19 setting.

Objective: The introduction of new endograft models improved long-term results of abdominal aortic aneurysm (AAA) endovascular repair (EVAR), but most of them maintained an old and unchanged design: a short body and long legs shifting up the flow divider. This study assessed the long-term results of EVAR with unimodular endoprosthesis fixed at the aorto-iliac bifurcation (Anatomical FiXation), in a large, unselected cohort. Materials and Methods: In a single-center, retrospective cohort study, 623 patients selectively treated between 1999 and 2016, were analyzed. Follow-up protocol included at least a computed tomography angiography within 3 months and a duplex ultrasound and clinical exam yearly. All enrolled patients were analyzed by 2020. The primary outcomes were technical success, clinical success, and survival. Secondary outcomes included survival-free from late-open-conversion (LOC), reintervention, and endoleaks. Results: Median age was 74±11 years and the follow-up 93±54 months. The technical success was achieved in 99.4% and the 30-day clinical success was 98.4%. A 5-year clinical success of 97.7% was registered and at 10 years success was 96.7%. The overall survival at 1, 5, 10, and 15 years was 92.4%, 79.5%, 64.9%, and 45.5%, respectively. Six (0.98%) AAA-related death were registered, 3 caused by infection of the endograft and 3 for secondary rupture. LOCs were 9 (1.47%) and reintervention-free survival at 1, 5, 10, and 15 years were 88.4%, 78.0%, 76.2%, and 74.6%, respectively. Freedom from endoleaks was 88.8% at 1 year and 72.7% at 15 years. A total of 63 high-flow endoleaks were registered (43 type I, 7 type IIIa, 12 type IIIb, and 1 type Ib+IIIb). No migrations were recorded, and the graft limb thrombosis rate was 1.14%. From a multivariate analysis resulted that long-term clinical success appeared to be reduced in patients affected by diabetes [odds ratio (OR) 0.24; p=0.04] and in presence of calcified and thrombotic iliac accesses (OR 0.16; p=0.006). Conclusion: EVAR with the Anatomical FiXation was confirmed to be safe, feasible, and effective to prevent AAA rupture in the long term as well. However, the overall survival remains afflicted by cardiovascular accident. The original concept of unibody bifurcated design allowed a very low rate of graft thrombosis and zeroed the risk of migration and related reintervention.

Background Intracranial hemorrhage (ICH) is a rare but devastating complication of thoracoabdominal aortic aneurysm (TAAA) repair with fenestrated/branched endograft (f/bEVAR). The cerebrospinal fluid drainage (CSFD) is considered one of the leading causes; however, other possible concomitant factors have not been individualized yet. The aim of the present work was to evaluate the pattern of ICH events after f/bEVAR for TAAA and to identify possible associated factors. Materials and Methods All f/bEVAR procedures for TAAA performed in a single academic center from 2012 to 2020 were evaluated. ICH was assessed by cerebral computed tomography if neurological symptoms arose. Pre-, intra-, and postoperative characteristics were analyzed in order to identify possible factors associated. Results A total of 135 f/bEVAR were performed for 72 (53%) type I, II, III and 63 (47%) type IV TAAA; 74 (55%) were staged procedures, 101 (73%) required CSFD, and 24 (18%) were performed urgently. The overall 30-day mortality was 8% (5% in elective cases); spinal-cord ischemia occurred in 11(8%) and ICH in 8 (6%) patients. All ICH occurred in patients with CSFD. ICH occurred intraoperatively in 1 case, inter-stage in 4 and after F/BEVAR completion in 3, after a median of 6 days the completion stage. Three (38%) of 8 patients with ICH died at 30 days and ICH was associated with 30-day mortality: odds ratio (OR) 13.2, 95% confidence interval (CI): 2.3–76, p=0.01. The analysis of the perioperative characteristics identified platelet reduction >60% (OR 11, 95% CI 1.6–77, p=0.03), chronic kidney disease (16% vs 0%, p=0.002), and total volume of liquor drained >50 mL (OR 8.1, 95% CI 1.1–69, p=0.03) as associated with ICH. Conclusions Current findings may suggest that ICH is a potential lethal complication of the endovascular treatment for TAAAs and it mainly occurs in patients with CSFD. High-volume liquor drainage, platelet reduction, and chronic kidney disease seems increase significantly the risk of ICH and should be considered during the perioperative period and for further studies.

OBJECTIVES: Hepatocellular carcinoma (HCC) has become a major issue in coinfected HIV/HCV patients with liver cirrhosis. We aimed to determine the rate of HCC occurrence after a direct-acting antiviral (DAA) treatment and to evaluate the factors associated with the risk of HCC in this population. DESIGN: We conducted a retrospective multicenter observational study including cirrhotic HIV/HCV-coinfected patients treated with DAAs, between October 2014 and January 2017. METHODS: We collected demographics characteristics, data regarding HIV and HCV infections and treatment with DAAs. We investigated the rate and the time of occurrence of HCC. Statistical analysis explored the factors associated to development of liver cancer. RESULTS: During a median follow-up of 55 months, 24 out of 232 patients developed HCC, after a median of 22.5 months from starting DAAs. Factors associated with HCC were a higher Child--Pugh Turcotte (CPT) score (P = 0.002), HCV genotype 3 (P = 0.04), previous HCC (P