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Introduction: Three-dimensional liver modeling can lead to substantial changes in choosing the type and extension of liver resection. This study aimed to explore whether 3D reconstruction helps to better understand the relationship between liver tumors and neighboring vascular structures compared to standard 2D CT scan images. Methods: Contrast-enhanced CT scan images of 11 patients suffering from primary and secondary hepatic tumors were selected. Twenty-three experienced HBP surgeons participated to the survey. A standardized questionnaire outlining 16 different vascular structures (items) having a potential relationship with the tumor was provided. Intraoperative and histopathological findings were used as the reference standard. The proper hypothesis was that 3D accuracy is greater than 2D. As a secondary endpoint, inter-raters’ agreement was explored. Results: The mean difference between 3D and 2D, was 2.6 points (SE: 0.40; 95 % CI: 1.7–3.5; p < 0.0001). After sensitivity analysis, the results favored 3D visualization as well (mean difference 1.7 points; SE: 0.32; 95 % CI: 1.0–2.5; p = 0.0004). The inter-raters’ agreement was moderate for both methods (2D: W = 0.45; 3D: W = 0.44). Conclusion: 3D reconstruction may give a significant contribution to better understanding liver vascular anatomy and the precise relationship between the tumor and the neighboring structures.

Translation of cell therapies into clinical practice requires the adoption of robust production protocols in order to optimize and standardize the manufacture and cryopreservation of cells, in compliance with good manufacturing practice regulations. Between 2012 and 2020, we conducted two phase I clinical trials (EudraCT 2009-014484-39, EudraCT 2015-004855-37) on amyotrophic lateral sclerosis secondary progressive multiple sclerosis patients, respectively, treating them with human neural stem cells. Our production process of a hNSC-based medicinal product is the first to use brain tissue samples extracted from fetuses that died in spontaneous abortion or miscarriage. It consists of selection, isolation and expansion of hNSCs and ends with the final pharmaceutical formulation tailored to a specific patient, in compliance with the approved clinical protocol. The cells used in these clinical trials were analyzed in order to confirm their microbiological safety; each batch was also tested to assess identity, potency and safety through morphological and functional assays. Preclinical, clinical and in vitro nonclinical data have proved that our cells are safe and stable, and that the production process can provide a high level of reproducibility of the cultures. Here, we describe the quality control strategy for the characterization of the hNSCs used in the above-mentioned clinical trials.

Background: In the aftermath of COVID-19 outbreak, there is a strong need to find strategies to monitor SARSCoV-2 transmission. While the application of screening techniques plays a major role to this end, there is evidence challenging the real significance of seroconversion. We reported a case of COVID-19 reactivation associated with a neurosurgical operation with early neuropsychiatric involvement presumably promoted by olfactory and gustatory impairment in the first infection. Case Descriptio: A 57-year-old man was referred for a 2-month history of progressive development of imbalance, dizziness, and vomiting. Magnetic resonance imaging showed two bilateral hemispheric cerebellar lesions. In line with our triage protocol, the patient underwent a nasopharyngeal swab for RNA of SARS-CoV-2 detection, which resulted positive. Of note, the patient had reported in the previous month hyposmia and hypogeusia. After a period of 14 days, three new swabs were performed with negative results, leading the way to surgery. In the early post-operative period, the patient manifested acute onset of psychotic symptoms with hyperactive delirium, followed by fever and acute respiratory failure. A chest computed tomography revealed a specific pattern of ground-glass opacities in the lower lobes bilaterally, suggesting a viral pneumonia. Serological tests demonstrated the seroconversion and a new nasopharyngeal swab confirmed SARS-CoV-2 infection. Conclusion: Our report highlights the importance of comprehensive screening assessments in sensitive cases highly susceptible to COVID-19 recurrence.

Background: The management of rectal cancer is multimodal and involves a multidisciplinary team of cancer specialists with expertise in medical oncology, surgical oncology, radiation oncology and radiology. It is crucial for highly specialized centers to collaborate via networks that aim to maintain uniformity in every aspect of treatment and rigorously gather patients’ data, from the first clinical evaluation to the last follow-up visit. The Advanced International Mini-Invasive Surgery (AIMS) academy clinical research network aims to create a rectal cancer registry. This will prospectively collect the data of patients operated on for non-metastatic rectal cancer in high volume colorectal surgical units through a well design pre-fashioned database for non-metastatic rectal cancer, in order to take all multidisciplinary aspects into consideration. Methods/Design: The protocol describes a multicenter prospective observational cohort study, investigating demographics, frailty, cancer-related features, surgical and radiological parameters, and oncological outcomes among patients with non-metastatic rectal cancer who are candidates for surgery with curative intent. Patients enrolled in the present registry will be followed up for 5 years after surgery. Discussion: Standardization and centralization of data collection for neoplastic diseases is a virtuous process for patient care. The creation of a register will allow the control of the quality of treatments provided and permit prospective and retrospective studies to be carried out on complete and reliable high quality data. Establishing data collection in a prospective and systematic fashion is the only possibility to preserve the enormous resource that each patient represents.

Introduction: Adjuvant chemotherapy for locally advanced rectal cancer is associated with improved overall survival. However, recent evidence from randomized trials showed a compliance rate of 43 to 73%, which may affect efficacy. The aim of this multicenter retrospective analysis was to investigate the compliance rate to adjuvant treatment for patients who underwent rectal surgery for cancer. Methods: Patients who underwent surgery with curative intent for rectal cancer in six Italian colorectal centers between January 2013 and December 2017 were retrospectively reviewed. Exclusion criteria were age less than 18 years, palliative or emergency surgery, and stage IV disease. Parameters of interest were patients’ characteristics, preoperative tumor stage, neo-adjuvant chemoradiation therapy, intra-operative and postoperative outcomes. Although the participating centers referred to the same treatment guidelines for treatment, the chemotherapy regiment was not standardized across the institutions. Reasons for not starting adjuvant chemotherapy when indicated, interruption, and modification of drug regimen were collected to investigate compliance. Results: A total of 572 patients were included in the analysis. Two hundred and fifty-two (44.1%) patients received neo-adjuvant chemoradiation therapy. All patients underwent high anterior rectal resection, low anterior rectal resection, or Miles’ procedure. Of 399 patients with an indication to adjuvant chemotherapy, 176 (44.1%) completed the treatment as planned. Compliance for patients who started chemotherapy was 56% (95% CI 50.4–61.6%). Sixty-six patients interrupted the treatment, 76 patients significantly reduced the drug dose, and 41 patients had to switch to other therapeutic regimens. Conclusions: The present multicenter investigation reports a low compliance rate to adjuvant chemotherapy after rectal resection for cancer. Multidisciplinary teams should focus on future effort to improve compliance for these patients.

Activated microglia/macrophages infiltration, astrocyte migration, and increased production of inhibitory chondroitin sulfate proteoglycans (CSPGs) are standard harmful events taking place after the spinal cord injuries (SCI). The gliotic scar, viz. the outcome of chronic SCI, constitutes a long-lasting physical and chemical barrier to axonal regrowth. In the past two decades, various research groups targeted the hostile host microenvironments of the gliotic scar at the injury site. To this purpose, biomaterial scaffolds demonstrate to provide a promising potential for nervous cell restoration. We here focused our efforts on two self-assembling peptides (SAPs), featuring different self-assembled nanostructures, and on different methods of drug loading to exploit the neuroregenerative potential of Chondroitinase ABC (ChABC), a thermolabile pro-plastic agent attenuating the inhibitory action of CSPGs. Enzymatic activity of ChABC (usually lasting less than 72 hours in vitro) released from SAPs was remarkably detected up to 42 days in vitro. ChABC was continuously released in vitro from a few days to 42 days as well. Also, injections of ChABC loaded SAP hydrogels favored host neural regeneration and behavioral recovery in chronic SCI in rats. Hence, SAP hydrogels showed great promise for the delivery of Chondroitinase ABC in future therapies targeting chronic SCI.

OBJECTIVE The COVID-19 pandemic has forced many countries into lockdown and has led to the postponement of nonurgent neurosurgical procedures. Although stress has been investigated during this pandemic, there are no reports on anxiety in neurosurgical patients undergoing nonurgent surgical procedures. METHODS Neurosurgical patients admitted to hospitals in eastern Lombardy for nonurgent surgery after the lockdown prospectively completed a pre- and postoperative structured questionnaire. Recorded data included demographics, pathology, time on surgical waiting list, anxiety related to COVID-19, primary pathology and surgery, safety perception during hospital admission before and after surgery, and surgical outcomes. Anxiety was measured with the State-Trait Anxiety Inventory. Descriptive statistics were computed on the different variables and data were stratified according to pathology (oncological vs nononcological). Three different models were used to investigate which variables had the greatest impact on anxiety, oncological patients, and safety perception, respectively. Because the variables (Xs) were of a different nature (qualitative and quantitative), mostly asymmetrical, and related to outcome (Y) by nonlinear relationships, a machine learning approach composed of three steps (1, random forest growing; 2, relative variable importance measure; and 3, partial dependence plots) was chosen. RESULTS One hundred twenty-three patients from 10 different hospitals were included in the study. None of the patients developed COVID-19 after surgery. State and trait anxiety were reported by 30.3% and 18.9% of patients, respectively. Higher values of state anxiety were documented in oncological compared to nononcological patients (46.7% vs 25%; p = 0.055). Anxiety was strongly associated with worry about primary pathology, surgery, disease worsening, and with stress during waiting time, as expected. Worry about positivity to SARS-CoV-2, however, was the strongest factor asso

Background: To verify the prognostic value of the pathologic and radiological tumor response after neoadjuvant chemotherapy in the treatment of locally advanced gastric adenocarcinoma. Methods: A total of 67 patients with locally advanced gastric cancer (clinical ≥ T2 or nodal disease and without evidence of distant metastases) underwent perioperative chemotherapy (ECF or ECX regimen) from December 2009 through June 2015 in two surgical units. Histopathological and radiological response to chemotherapy were evaluated by using tumor regression grade (TRG) (Becker's criteria) and volume change assessed by CT. Results: Fifty-one (86%) patients completed all chemotherapy scheduled cycles successfully and surgery was curative (R0) in 64 (97%) subjects. The histopathological analysis showed 19 (29%) specimens with TRG1 (less than 10% of vital tumor left) and 25 (37%) patients had partial or complete response (CR) assessed by CT scan. Median disease free survival (DFS) and overall survival (OS) were 25.70 months (range, 14.52-36.80 months) and 36.60 months (range, 24.3-52.9 months), respectively. The median follow up was 27 months (range, 5.00-68.00 months). Radiological response and TRG were found to be a prognostic factor for OS and DFS, while tumor histology was not significantly related to survival. Conclusions: Both radiological response and TRG have been shown as promising survival markers in patients treated with perioperative chemotherapy for locally advanced gastric cancer. Other predictive markers of response to chemotherapy are strongly required.

Three-dimensional cell cultures are leading the way to the fabrication of tissue-like constructs useful to developmental biology and pharmaceutical screenings. However, their reproducibility and translational potential have been limited by biomaterial and culture media compositions, as well as cellular sources. We developed a construct comprising synthetic multifunctionalized hydrogels, serum-free media, and densely seeded good manufacturing practice protocol-grade human neural stem cells (hNSC). We tracked hNSC proliferation, differentiation, and maturation into GABAergic, glutamatergic, and cholinergic neurons, showing entangled electrically active neural networks. The neuroregenerative potential of the "engineered tissue" was assessed in spinal cord injuries, where hNSC-derived progenitors and predifferentiated hNSC progeny, embedded in multifunctionalized hydrogels, were implanted. All implants decreased astrogliosis and lowered the immune response, but scaffolds with predifferentiated hNSCs showed higher percentages of neuronal markers, better hNSC engraftment, and improved behavioral recovery. Our hNSC-construct enables the formation of 3D functional neuronal networks in vitro, allowing novel strategies for hNSC therapies in vivo

Wayforlight.eu is the gateway to finding the most suitable instruments for experiments with synchrotron, FEL, and laser light sources. The portal's main asset is a detailed searchable catalogue of facilities, beamlines, and instrumentation available at European light sources. Thanks to its advanced search tools, a visitor can filter beamlines by scientific discipline, by technique, but also by energy range or sample type.

Stem-cell behavior is regulated by the material properties of the surrounding extracellular matrix, which has important implications for the design of tissue-engineering scaffolds. However, our understanding of the material properties of stem-cell scaffolds is limited to nanoscopic-to-macroscopic length scales. Herein, a solid-state NMR approach is presented that provides atomic-scale information on complex stem-cell substrates at near physiological conditions and at natural isotope abundance. Using self-assembled peptidic scaffolds designed for nervous-tissue regeneration, we show at atomic scale how scaffold-assembly degree, mechanics, and homogeneity correlate with favorable stem cell behavior. Integration of solid-state NMR data with molecular dynamics simulations reveals a highly ordered fibrillar structure as the most favorable stem-cell scaffold. This could improve the design of tissue-engineering scaffolds and other self-assembled biomaterials.

BACKGROUND Preoperative chemotherapy improves the outcome in patients with colorectal cancer with liver metastases. In the current study, the authors evaluated the activity of a conversion treatment with the combination of capecitabine plus oxaliplatin (XELOX) used in association with panitumumab in patients with unresectable, liver-only, metastatic colon cancer. METHODS Chemotherapy-naive patients with unresectable liver metastases from colon cancer with no other metastatic disease sites were enrolled. All patients received upfront therapy with XELOX plus panitumumab (P-XELOX) and were reevaluated for resectability every 4 cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints were overall survival (OS), progression-free survival, the percentage of patients whose disease became radically resectable, and the safety of the P-XELOX combination. RESULTS A total of 49 patients were recruited, 35 of whom had wild-type KRAS (wtKRAS) and 14 of whom (who were enrolled before study amendment) had unknown (9 patients) or mutated (5 patients) KRAS mutational status. Forty-six patients were evaluable for response. After conversion P-XELOX therapy, the ORR in the general population was 54%, with 2 complete responses, 23 partial responses, and 14 cases of stable disease. In patients with wtKRAS, the ORR of the patients reached 65% (2 CRs and 19 PRs), which allowed 15 patients with initial unresectable liver metastasis to be reclassified as having resectable disease. Survival analysis demonstrated a median progression-free survival of 8.5 months and a median OS of 21.9 months. Patients who underwent surgery were found to have a significantly better OS when compared with those who did not undergo surgery (P <.001). Overall, toxicities were found to be predictable and manageable, with the most common being cutaneous, gastrointestinal, and neurologic toxicities. CONCLUSIONS Conversion P-XELOX therapy yields high response and resectability rates for pa

Aim: To evaluate by immumohistochemistry the presence of DR subtype 2 (D2R) in well differentiated NETs of different sites and in normal islet cells. Background: Recent data in vitro and in vivo support that dopaminergic drugs might exert an inhibitory effect on hormone secretion and, possibly, on tumor growth in neuroendocrine tumors (NET)s. Their potential therapeutic role needs the demonstration of dopamine receptors (DR) in tumor cells. Little is known on the expression of DR in NETs. Results: 85% of samples (100% of bronchial carcinoids and 93% of islet cell tumors) showed positivity for D2R; intensity of immunoreaction in NETs was similar or higher than in pituitary (54% and respectively 31% of cases). D2R positivity in more than 70% of tumor cells was observed in 46% of samples. Same intensity of D2R-immunoreactivity was found in pituitary and normal islet cells. No differences in D2R expression were recorded on considering tumor grading, size, proliferative activity, presence of metastases, endocrine activity and gender. A significant difference (62.5% vs 96.4%, p = 0.039) was observed in the prevalence of D2R expression between patients with more aggressive tumors and patients without recurrence/progression of disease during follow-up. Methods: 46 NET samples from 44 patients and normal endocrine pancreatic tissue were studied. D2R-staining was performed on NETs and compared with six non-secreting pituitary adenomas and related to clinical-pathological data. Conclusion: The present data demonstrate a high expression of D2R in NETs; this finding is of clinical relevance in view of the potential role of dopaminergic drugs in inhibiting secretion and/or cell proliferation in NETs. ©2008 Landes Bioscience.

The impact of an azimuthal slot in the antenna flair on the performance of a bowtie antenna has been analyzed. It has been shown that the slot is equivalent to resistance-capacitance loading. The resistance of the slot is physically caused by radiation of electromagnetic energy from the slot. Equivalent resistance and capacitance of the slot have been analyzed against geometrical parameters and frequency. The azimuthal slot has been used to improve the bowtie performance and to optimize this antenna for an ultrawideband impulse radio system under development. After optimization, the antenna exhibits a better performance than the conventional bowtie in terms of efficiency, late-time ringing, and matching to the generator/receiver. The performance of the optimized antenna has been verified experimentally; good agreement between theory and experiment has been observed., Telecommunications, Electrical Engineering, Mathematics and Computer Science