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How histopathological diagnosis interacts with kidney ultrasound parameters to predict glomerular filtration rate

Abstract Background eGFR evaluation is a pivotal staging step in patients with chronic kidney disease (CKD), and renal ultrasound plays an important role in diagnosis, prognosis and progression of CKD. The role of the interaction between histopathological diagnosis and ultrasound parameters in the eGFR determination has not been fully investigated yet.Methods The study examined the results of native kidney biopsies performed in 48 Italian centers between 2012 and 2020. The primary goal was if and how the histopathological diagnosis influences the relationship between eGFR and ultrasound parameters.Results After exclusion of children, patients with acute kidney injury and patients without measure of kidney length or parenchymal thickness, 2795 patients have been selected for analysis. The median values were 52 years for patient age, 11 cm for bipolar kidney diameter, 16 mm for parenchymal thickness, 2.5 g/day for proteinuria and 70 ml/min/1.73 m2 for eGFR. The bipolar kidney diameter and the parenchymal thickness predict eGFR values (R square 0.064). Diabetes and proteinuria were associated with a consistent reduction of eGFR, improving the adjusted R square up to 0.100. Addition of histopathological diagnosis in the model increased the adjusted R square to 0.216. There is a significant interaction between histopathological diagnosis and longitudinal kidney diameter (P 0.006).Conclusions Renal bipolar length and parenchymal thickness are directly related with eGFR. The magnitude of proteinuria and histopathological kidney diagnosis increased the prediction of eGFR. The association between the kidney length and the level of eGFR depends on the nature of the kidney disease.

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High-resolution CT phenotypes in pulmonary sarcoidosis: a multinational Delphi consensus study

One view of sarcoidosis is that the term covers many different diseases. However, no classification framework exists for the future exploration of pathogenetic pathways, genetic or trigger predilections, patterns of lung function impairment, or treatment separations, or for the development of diagnostic algorithms or relevant outcome measures. We aimed to establish agreement on high-resolution CT (HRCT) phenotypic separations in sarcoidosis to anchor future CT research through a multinational two-round Delphi consensus process. Delphi participants included members of the Fleischner Society and the World Association of Sarcoidosis and other Granulomatous Disorders, as well as members' nominees. 146 individuals (98 chest physicians, 48 thoracic radiologists) from 28 countries took part, 144 of whom completed both Delphi rounds. After rating of 35 Delphi statements on a five-point Likert scale, consensus was achieved for 22 (63%) statements. There was 97% agreement on the existence of distinct HRCT phenotypes, with seven HRCT phenotypes that were categorised by participants as non-fibrotic or likely to be fibrotic. The international consensus reached in this Delphi exercise justifies the formulation of a CT classification as a basis for the possible definition of separate diseases. Further refinement of phenotypes with rapidly achievable CT studies is now needed to underpin the development of a formal classification of sarcoidosis.

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Stroke pathway performance assessment: a retrospective observational study

Background and AimPerformance assessment of the Stroke Pathway is a key element in healthcare quality. The aim of this study has been to carry out a retrospective assessment of the Stroke Pathway in a first level Stroke Unit in Italy, analyzing the temporal trend of the Stroke Pathway performance and the impact of the COVID-19 pandemic.MethodsA retrospective observational study was carried out analyzing data from 1/01/2010 to 31/12/2020. The following parameters were considered: volume and characteristics of patients with ischemic stroke undergoing intravenous thrombolysis, baseline modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) scores, Onset-to-Door (OTD), Door-To-Imaging (DTI) and Door-To-Needle (DTN) Times, mRS score 3 months after the ischemic event onset (3 m-mRS) and NIHSS score 24 h after the ischemic event onset (24 h-NIHSS). The study also compared the pre-COVID-19 pandemic period (March-December 2019) with the one immediately following it (March-December 2020).Results418 patients were included. Over time, treatment was extended to older patients (mean age from 66.3 to 75.51 years; p = 0.006) and with a higher level of baseline disability (baseline mRS score from 0.22 to 1.22; p = 0.000). A statistically significant reduction over the years was found for DTN, going from 90 min to 61 min (p = 0.000) with also an increase in the number of thrombolysis performed within the “golden hour” – more than 50% in 2019 and more of 60% in 2020. Comparing pre- and during COVID-19 pandemic periods, the number of patients remained almost unchanged, but with a significantly higher baseline disability (mRS = 1.18 vs. 0.72, p = 0.048). The pre-hospital process indicator OTD increased from 88.13 to 118.48 min, although without a statistically significant difference (p = 0.197). Despite the difficulties for hospitals due to pandemic, the hospital process indicators DTI and DTN remained substantially unchanged, as well as the clinical outcome indicators 3 m-mRS, NHISS and 24 h-NHISS.ConclusionsThe results of the retrospective assessment of the Stroke Pathway highlighted its positive impact both on hospital processes and patients’ outcomes, even during the COVID-19 pandemic, so that the current performance is aligning itself with international goals. Moreover, the analysis showed the need of improvement actions for both hospital and pre-hospital phases. The Stroke Pathway should be improved with the thrombolysis starting in the diagnostic imaging department in order to further reduce the DTN score. Moreover, health education initiatives involving all the stakeholders should be promoted, also by using social media, to increase population awareness on timely recognition of stroke signs and symptoms and emergence medical services usage.

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Endoscopic full-thickness resection vs. endoscopic submucosal dissection of residual/recurrent colonic lesions on scars: a retrospective Italian and Japanese comparative study.

Endoscopic treatment of recurrent/residual colonic lesions on scars is a challenging procedure. In this setting, endoscopic submucosal dissection (ESD) is considered the first choice, despite a significant rate of complications. Endoscopic full-thickness resection (eFTR) has been shown to be well-tolerated and effective for these lesions. The aim of this study is to conduct a comparison of outcomes for resection of such lesions between ESD and eFTR in an Italian and a Japanese referral center. From January 2018 to July 2020, we retrospectively enrolled patients with residual/recurrent colonic lesions, 20 treated by eFTR in Italy and 43 treated by ESD in Japan. The primary outcome was to compare the two techniques in terms of en-bloc and R0-resection rates, whereas complications, time of procedure, and outcomes at 3-month follow-up were evaluated as secondary outcomes. R0 resection rate was not significantly different between the two groups [18/20 (90%) and 41/43 (95%); P= 0.66]. En-bloc resection was 100% in both groups. No significant difference was found in the procedure time (54 min vs. 61 min; P= 0.9). There was a higher perforation rate in the ESD group [11/43 (26%) vs. 0/20 (0%); P= 0.01]. At the 3-month follow-up, two lesions relapsed in the eFTR cohort and none in the ESD cohort (P= 0.1). eFTR is a safer, as effective and equally time-consuming technique compared with ESD for the treatment of residual/recurrent colonic lesions on scars and could become an alternative therapeutic option for such lesions.

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Role of CDK4 as prognostic biomarker and synergistic effect of its inhibition in dedifferentiated liposarcoma sequential treatment

Abstract Background Soft tissue sarcomas represent a heterogeneous group of rare mesenchymal tumors comprising 1% of all solid malignancies. Among them liposarcoma is one of the most common histotypes, with atypical lipomatous tumor/well differentiated liposarcoma and dedifferentiated liposarcoma (ALT/WDLPS and DDLPS) as the major sub entities. The unavailability of predictive, prognostic and druggable biomarkers make the management of these lesions challenging. In recent years, CDK4 and its inhibitors have emerged as potential weapons for these lesions especially for ALT/WDLPS and DDLPS but the results are not conclusive and need to be elucidated. Methods This study involved 21 ALT/WDLPS and DDLPS patients. Histological analyses of MDM2 and CDK4 were carried out. Moreover, a DDLPS patient-derived cancer model was established in vitro and in vivo assessing the efficacy of palbociclib in combination and sequential treatment. Finally, in silico analyses on CDK4 expression were carried out. Results The results showed a higher expression of CDK4 and MDM2 in DDLPS compared to ALT/WDLPS. Moreover, no correlation between MDM2 expression and CDK4 was observed. In addition, CDK4 expression seemed to correlate with specific anatomic regions. Next, in vitro analysis of CDK4 inhibitor palbociclib showed an antagonistic effect when combined to other chemotherapeutics, while it exhibited a significant synergy when administered in sequential schedule in both 2D and 3D culture models with ifosfamide, ifosfamide plus epirubicin, trabectedin, dacarbazine, eribulin and lenvatinib. The data were further corroborated by scratch wound healing assay and live-dead analysis. Next, in vivo analysis on DDLPS xenotransplanted embryos assessing the efficacy and safety profile of the in vitro tested schedules confirmed the observed data. Finally, in silico analysis supported the role of CDK4 in sarcoma management, especially DDLPS. Conclusion This proof-of-concept study sheds light on the natural history of ALT/WDLPS and DDLPS and provides the rationale for the clinical applicability of sequential treatment with palbociclib in the management of DDLPS.

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Cytoreduction Plus Hyperthermic Intraperitoneal Chemotherapy in Primary and Recurrent Ovarian Cancer: A Single-Center Cohort Study

Epithelial ovarian cancer (EOC) is the most frequent cause of death among women with gynecologic malignant tumors. Primary debulking surgery (PDS) with maximal surgical effort to reach completeness of cytoreduction, followed by chemotherapy, has become the standard of care; moreover, some experiences have shown that a comprehensive treatment approach of surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) could improve the prognosis of ovarian cancer. We carried out a retrospective analysis of all consecutive sixty-six patients diagnosed with primary advanced or recurrent ovarian cancer who underwent debulking surgery plus HIPEC in a single center between September 2005 and October 2020. For 33 patients with primary EOC, with a median follow-up period of 70 months, the median overall survival was 56 months (range: 48.1–96.9); and the median disease-free survival (DFS) was 13 months (range: 19.9–53.7). In the recurrent population, the median follow-up period was 78 months, the median overall survival (OS) was 82 months (range: 48.1–96.9), and the median DFS was 17 months (range: 19.7–53.0). In our study, we have found that CRS plus HIPEC is feasible, with very low rates of major complications and good results in terms of overall survival.

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