Thrombin regulates the ability of Schwann cells to support neuritogenesis and to maintain the integrity of the nodes of Ranvier

Schwann cells (SC) are characterized by a remarkable plasticity that enables them to promptly respond to nerve injury promoting axonal regeneration. In peripheral nerves after damage SC convert to a repair-promoting phenotype activating a sequence of supportive functions that drive myelin clearance, prevent neuronal death, and help axon growth and guidance. Regeneration of peripheral nerves after damage correlates inversely with thrombin levels. Thrombin is not only the key regulator of the coagulation cascade but also a protease with hormone-like activities that affects various cells of the central and peripheral nervous system mainly through the protease-activated receptor 1 (PAR1). Aim of the present study was to investigate if and how thrombin could affect the axon supportive functions of SC. In particular, our results show that the activation of PAR1 in rat SC cultures with low levels of thrombin or PAR1 agonist peptides induces the release of molecules, which favor neuronal survival and neurite elongation. Conversely, the stimulation of SC with high levels of thrombin or PAR1 agonist peptides drives an opposite effect inducing SC to release factors that inhibit the extension of neurites. Moreover, high levels of thrombin administered to sciatic nerve ex vivo explants induce a dramatic change in SC morphology causing disappearance of the Cajal bands, enlargement of the Schmidt-Lanterman incisures and calcium-mediated demyelination of the paranodes. Our results indicate thrombin as a novel modulator of SC plasticity potentially able to favor or inhibit SC pro-regenerative properties according to its level at the site of lesion

Surgical and Bioengineering Integration in the Anatomy Course of Medicine and Surgery High Technology: Knowledge and Perception of Anatomy

The Locomotor System Anatomy (LSA) course, placed in the first semester of the first year of the new Master’s degree in Medicine and Surgery High Technology (MSHT) at the Sapienza University of Rome, was integrated with surgical and bioengineering content. This study investigated the educational value and the students’ perceptions of the effectiveness of these two types of integration, comparing surgical integration (SI) with engineering integration (EI). Anatomy knowledge and students’ opinions attending the LSA course in MSHT degree (n = 30) were compared with those of students (n = 32) attending another medical and surgery course not comprising EI. Data show that students in the MSHT course like in-depth SI much more than in-depth EI. However, those who like in-depth SI also like in-depth EI. Significant differences were in anatomy knowledge between the two groups in the three sections of the test. There was no significant correlation between the three test scores and the levels of liking, while there was a significant correlation between students liking SI and those liking EI. A statistically significant correlation was also found in students who correctly responded to questions on the head and trunk, with students responding correctly to questions on the upper limbs. This study will be important in optimizing the deepening of SI and EI in the LSA course. Keywords: human anatomy; anatomical sciences education; gross anatomy teaching; locomotor system; neurosurgery; orthopedics; surgical integration; bioengineering integration; technical physician; technical medicin

Adult IDH wild-type glioblastoma ultrastructural investigation suggests a possible correlation between morphological biomarkers and Ki-67 index

Glioblastoma is an aggressive brain tumor with an average life expectancy between 14 and 16 months after diagnosis. The Ki-67 labeling index (LI), a measure of cellular proliferation, is emerging as a prognostic marker in GBM. In this study, we investigated the ultrastructure of glioblastoma tissue from 9 patients with the same molecular profile (adult IDH wild-type glioblastoma, wild-type ATRX, and positive for TP53 expression, GFAP expression, and EGFR overexpression) to find possible ultrastructural features to be used as biomarkers and correlated with the only parameter that differs among our samples, the Ki-67 LI. Our main results were the visualization of the anatomical basis of astrocyte-endothelial cells crosstalk; the ultrastructural in situ imaging of clusters of hyperactivated microglia cells (MsEVs); the ultrastructural in situ imaging of microglia cells storing lipid vesicles (MsLVs); the ultrastructural in situ imaging of neoplastic cells mitophagy (NCsM). The statistical analysis of our data indicated that MsEVs and MsLVs correlate with the Ki-67 LI value. We can thus assume they are good candidates to be considered morphological biomarkers correlating to Ki-67 LI. The role of NCsM instead must be further evaluated. Our study findings demonstrate that by combining ultrastructural characteristics with molecular information, we can discover biomarkers that have the potential to enhance diagnostic precision, aid in treatment decision-making, identify targets for therapy, and enable personalized treatment plans tailored to each patient. However, further research with larger sample sizes is needed to validate these findings and fully utilize the potential of ultrastructural analysis in managing glioblastoma

Clinically integrated neuroanatomy modules using neurosurgery and intraoperative MRI/DTI tractography: their contribution to long-term retention of neuroanatomical knowledge

Neuroanatomy is often considered the part of the human anatomy syllabus students find hardest to study. To motivate them and boost their learning, clinical cases and neurosurgical images, mainly DTI tractographies produced using an intraoperative magnetic resonance imaging apparatus (MRI/DTI), were presented and discussed during integrated second-year neuroanatomy, neuroradiology and neurosurgery lectures over the five-year 2007-2012 period. Anonymous questionnaires, rated on the Likert scale, showed that the students appreciated this teaching procedure. The academic performance (exam marks for neuroanatomy) of those who attended all the integrated lectures, was slightly, though significantly higher than for students who attended the lectures only occasionally or not at all (p=0.04). Moreover, significantly better results were obtained at the 2012 national progress test (focusing on morphology) by students who attended the MRI/DTI-assisted lectures, compared to those who did so in part or not at all and compared to the national average. These results were obtained by students attending the second, third and, in particular, the fourth, fifth and sixth year (p≤0.0001) courses during the five above-mentioned academic years. The early study of real medical cases, including the relative surgical and post-operative phases, if illustrated by a good collaborative interdisciplinary team, can help direct the students positively towards their future professional reality, without any extra expense to the university. In conclusion, interactive learning tools, like our intraoperative MRI/DTI, motivate students and enhance their learning of neuroanatomy. Most probably it improves long-term retention, which appears to prove helpful during the clinical phase of their undergraduate careers

RET/PTC3 translocation in a rare hemorrhagic brain metastasis of papillary thyroid cancer post Chernobyl radiation affects vessels ultrastructure

Abstract Background Slow progression and good prognosis are the usual characteristics of papillary thyroid carcinoma (PTC). The presence of brain metastases (0.4–1.2%) is suggestive of a worse prognosis. RET/PTC rearrangements were particularly prevalent in PTCs developed after Chernobyl nuclear accident. Case description A 50-year-old woman born in Slovakia, exposed to radiation resulting from the accident at the Chernobyl nuclear power plant, affected since 2017 by papillary thyroid cancer and in therapy at our hospital, experimented cerebral hemorrhagic metastasis. Biopsy analyses revealed a RET/PTC3 rearrangement, so our aim was to find possible morphological relation between hemorrhagic metastasis and RET/PTC3 translocation. Results Immunohistochemical analysis showed diffuse and intense positivity for VEGF in endothelial cells of the neoplasm’ vascular network. Transmission electron microscopy images showed vessels with unorganized pattern and uneven diameters. In particular, metastasis endothelial cells (MECs) showed irregular shape and size, thickened cytoplasm and swelling of endoplasmic reticulum. MECs organized in irregular monolayers or multiple layers, surrounded by a thickened but unstructured extracellular matrix. Absence of strong junctional complexes among MECs resulted in a further weakened vessels wall. Conclusion RET/PTC3 translocation causes VEGF overexpression via STAT3 signaling cascade and the increased amount of VEGF adds to the greater amount of VEGFRs expressed by MECs. Our ultrastructural investigation show that this condition creates a massive growth of altered vessels prone to bleeding. The clinical significance of our study consists in alert oncologist and surgeons on possible arising of hemorrhagic brain metastases in patients with PTC and RET/PTC3 translocation exposed to ionizing radiation as people living in areas caught up in Chernobyl or Fukushima disasters

Development of a Novel Device for Decompressive Craniectomy: An Experimental and Cadaveric Study and Preliminary Clinical Application

Background: Decompressive craniectomy is an intervention of established efficacy in patients with intractable cerebral edema. Objective: To evaluate a new device used in alternative to decompressive craniectomy. This device is designed to perform an augmentative craniotomy by keeping the bone flap elevated using specific cranial suspension titanium plates and giving the brain enough room to swell. Methods: We tested the mechanical characteristics of the cranial brackets on dried skulls, on 3D-printed skull models, and on a preserved cadaver head. The resistance of the device was examined through dynamometric testing, and the feasibility of the surgical technique, including the suspension of the bone flap and the skin closure, was investigated on the cadaveric model. A preliminary clinical series of 2 patients is also reported. Results: The laboratory tests have shown that this system allows an adequate expansion of the intracranial volume and it could withstand a force up to 637 ± 13 N in the synthetic model and up to 658 ± 9 N in the human skull without dislocation or failure of the brackets nor fractures of the bone ridges. Preliminary application in the clinical setting has shown that augmentative craniotomy is effective in the control of intracranial hypertension and could reduce the costs and complications associated with the classical decompressive craniectomy technique. Conclusion: Preliminary laboratory and clinical results show augmentative craniotomy to be a promising, alternative technique to decompressive craniectomy. Further clinical studies will be needed to validate its efficacy

Efficacy and safety of primary, early and late needle-knife fistulotomy for biliary access

European Society of Gastrointestinal Endoscopy recommends needle-knife fistulotomy (NKF) as the preferred precut technique. However, there is little information on whether NKF performed at different times is associated with different success and adverse event rates. We compared the outcomes of 3 different timings of NKF. This was an observational study conducted at 4 institutions and this was a retrospective analysis of prospectively collected data. We included 330 consecutive patients submitted to NKF attempt for biliary access. Patients were divided into three groups: NKF as an initial procedure for biliary access (group A, n = 121); early NKF defined as after 5 min, 5 attempts, or 2 pancreatic passages (group B, n = 99); and late NKF: after at least 10 min of unsuccessful standard biliary cannulation (group C, n = 110). We assessed the success rate of biliary cannulation at initial ERCP, time to perform NKF until biliary cannulation, overall biliary cannulation rate (second ERCP when initial failure), adverse event rate, and predictors of post-ERCP pancreatitis (PEP). The initial cannulation rate was 98%, 91% and 94% for groups A, B and C respectively, p = 0.08, whereas overall biliary cannulation rate was 100%, 95% and 98%, p = 0.115. The adverse event rate/PEP was 4.1%/2.5%, 7.1%/4% and 10.9%/8.2%, for groups A, B and C respectively, (p = 0.197 and p = 0.190). Median time for creating the fistula was A = 4.0 min, B = 3.2 min, and C = 5.6 min, p < 000.1. Each additional minute spent attempting cannulation increased the odds ratio (OR) for PEP by 1.072, and patients with 3 or more risk factors for pancreatitis had a higher chance of PEP. In conclusion, the timing of NFK does not appear to influence success rates but late NFK is associated with a higher time to create a fistula and an increased risk of pancreatitis. Primary NFK is associated with a high rate of success and a low rate of PEP and deserves additional investigation.publishersversionpublishe

Giant endobronchial hamartoma resected by fiberoptic bronchoscopy electrosurgical snaring

Less than 1% of lung neoplasms are represented by benign tumors. Among these, hamartomas are the most common with an incidence between 0.025% and 0.32%. In relation to the localization, hamartomas are divided into intraparenchymal and endobronchial

Influence of a novel classification of the papilla of Vater on the outcome of needle-knife fistulotomy for biliary cannulation

BACKGROUND: Existing proposed classification systems for the Papilla of Vater (PV) suboptimally account for all relevant, encountered PV appearances, are too complex or have not been assessed for intra- or interobserver variability. We proposed a novel endoscopic classification system for PV, determined its inter- and intraobserver rates and used the classification system to assess whether the success and complications of needle-knife fistulotomy (NKF) are influenced by the morphology of the PV. METHODS: The classification system was developed by expert endoscopists. To evaluate the inter- and intraobserver agreement, an online questionnaire was sent to 20 endoscopists from several countries (10 experts and 10 nonexperts) that included 50 images of papillae of Vater divided among various categories. Four weeks later, a second survey, with the images from the first questionnaire randomly reordered, was sent to the same endoscopists. The inter- and intraobserver agreements among the experts and nonexperts was calculated. Using the proposed classification system, all 361 consecutive patients who underwent NKF for biliary access to a naïve papilla were prospectively enrolled in the study. RESULTS: The novel classification system comprises 7 categories: type I, flat type, lacking an oral protrusion; type IIA, prominent tubular nonpleated type, with an oral protrusion and  2 transverse folds over the oral protrusion; type IIC: prominent bulging type, with an enlarged and bulging oral protrusion; type IIIA, diverticular-intradiverticular type, with a papillary orifice inside the diverticulum; type IIIB: diverticular-diverticular border type, with a papillary orifice less than 2 cm from the diverticular border; type IV: unclassified papilla, with no morphology classified in the other categories. The interobserver agreement between experts was substantial (K = 0.611, 95% CI 0.498-0.709) and was higher than that between nonexperts (K = 0.516; 95% CI 0.410-0.636). The intraobserver agreement was substantial among both experts (K = 0,651; 95% CI 0.586-0.715) and nonexperts (K = 0.646, 95% CI 0.615-0.677). In a multivariate model, type IIIA and IIIB were the only independent risk factors for difficult rescue NKF biliary cannulation (P = 0.003 and P = 0.019, respectively), and type I and type IIB were the only independent risk factors for a prolonged cannulation time using NKF (P < 0.001 and P = 0.005, respectively). CONCLUSIONS: The novel endoscopic classification system for PV is highly reproducible among experienced ERCPists according to the substantial level of agreement between experts. However, nonexperts require further training in its use. Using the novel classification system, we identified different types of papillae significantly associated with a lower efficacy of NKF and a prolonged time to obtain successful biliary cannulation using NKF.publishersversionpublishe