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Although the immunotherapy advent has revolutionized cancer treatment, it, unfortunately, does not spare cancer patients from possible immune-related adverse events (irAEs), which can also involve the peripheral nervous system. Immune checkpoint inhibitors (ICIs), blocking cytotoxic T-lymphocyteassociated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death ligand 1 (PD-L1), can induce an immune imbalance and cause different peripheral neuropathies (PNs). Considering the wide range of PNs and their high impact on the safety and quality of life for cancer patients and the availability of large post-marketing surveillance databases, we chose to analyze the characteristics of ICI-related PNs reported as suspected drug reactions from 2010 to 2020 in the European real-world context. We analyzed data collected in the European pharmacovigilance database, Eudravigilance, and conducted a systematic and disproportionality analysis. In our study, we found 735 reports describing 766 PNs occurred in patients treated with ICIs. These PNs included Guillain-Barré syndrome, Miller-Fisher syndrome, neuritis, and chronic inflammatory demyelinating polyradiculoneuropathy. These ADRs were often serious, resulting in patient disability or hospitalization. Moreover, our disproportionality analysis revealed an increased reporting frequency of PNs with tezolizumab compared to other ICIs. Guillain-Barré syndrome is a notable potential PN related to ICIs, as it is associated with a significant impact on patient safety and has had unfavorable outcomes, including a fatal one. Continued monitoring of the safety profile of ICIs in real-life settings is necessary, especially considering the increased frequency of PNs associated with atezolizumab compared with other ICIs.

OBJECTIVE: Recently, Zirconia and polyaryletherketone (PEEK) have attracted increasing interest as reliable and safe materials in dental applications, mainly because of their good biomechanical characteristics. The aim of this study was to investigate the response to different loads by prosthetic frameworks for supported fixed partial dentures (FPDs), thus simulating osseointegrated implants. MATERIALS AND METHODS: The specimens were divided into two groups (n= 5 each). Group A: FDPs in zirconia-ceramic; Group B: FDPs in PEEK-composite. These 2 groups were subjected to vertical loads so to evaluate structural deformation; then, they have been analyzed by scanning electron microscopy (SEM) at different magnifications. RESULTS: In tested samples, different types of mechanical failures have been observed. In Zirconia-specimens, chipping is the main failure noticed in this study, mostly in distal margins of the structure. Also, peek-specimens show failure and fracture. CONCLUSIONS: Zirconia and PEEK could be considered both good materials, but several investigations are needed to use these materials as an alternative to metals for fixed partial dentures.

Background Coronary access after transcatheter aortic valve implantation (TAVI) with supra-annular self-expandable valves may be challenging or un-feasible. There is little data concerning coronary access following transcatheter aortic valve-in-valve implantation (ViV-TAVI) for degenerated surgical bioprosthesis Aims To evaluate the feasibility and challenge of coronary access after ViV-TAVI with the supra-annular self-expandable ACURATE neo valve. Methods Sixteen patients underwent ViV-TAVI with the ACURATE neo valve. Post-procedural computed tomography (CT) was used to create 3D-printed life-sized patient-specific models for bench-testing of coronary cannulation. Primary endpoint was feasibility of diagnostic angiography and PCI. Secondary endpoints included incidence of challenging cannulation for both diagnostic catheters (DC) and guiding catheters (GC). The association between challenging cannulations with aortic and transcatheter/surgical valve geometry was evaluated using pre and post-procedural CT scans. Results Diagnostic angiography and PCI were feasible for 97% and 95% of models respectively. All non-feasible procedures occurred in ostia that underwent prophylactic ‘chimney’ stenting. DC cannulation was challenging in 17% of models and was associated with a narrower SoV width (30mm vs. 35mm, p

Background Laparoscopic cholecystectomy is considered the gold standard for the treatment of gallbladder lithiasis; nevertheless, the incidence of bile duct injuries (BDI) is still high (0.3–0.8%) compared to open cholecystectomy (0.2%). In 1995, Strasberg introduced the "Critical View of Safety" (CVS) to reduce the risk of BDI. Despite its widespread use, the scientific evidence supporting this technique to prevent BDI is controversial. Methods Between March 2017 and March 2019, the data of patients submitted to laparoscopic cholecystectomy in 30 Italian surgical departments were collected on a national database. A survey was submitted to all members of Italian Digestive Pathology Society to obtain data on the preoperative workup, the surgical and postoperative management of patients and to judge, at the end of the procedure, if the isolation of the elements was performed according to the CVS. In the case of a declared critical view, iconographic documentation was obtained, finally reviewed by an external auditor. Results Data from 604 patients were analysed. The study population was divided into two groups according to the evidence (Group A; n = 11) or absence (Group B; N = 593) of BDI and perioperative bleeding. The non-use of CVS was found in 54.6% of procedures in the Group A, and 25.8% in the Group B, and evaluating the operator-related variables the execution of CVS was associated with a significantly lower incidence of BDI and intraoperative bleeding. Conclusions The CVS confirmed to be the safest technique to recognize the elements of the Calot triangle and, if correctly performed, it significantly impacted on preventing intraoperative complications. Additional educational programs on the correct application of CVS in clinical practice would be desirable to avoid extreme conditions that may require additional procedures.

Viene descritto un sistema (1) per l’acquisizione di immagini e la ricostruzione digitale tridimensionale di forme anatomiche umane comprendente una pluralità di elementi (2) per l’acquisizione istantanea e sincronizzata di immagini e per l’invio, opzionalmente in modalità wireless, di informazioni associate alle immagini acquisite, un’unità di elaborazione centrale (4) per la ricostruzione di un modello digitale tridimensionale a partire da queste informazioni, un dispositivo di controllo (9) in grado di trasmettere a detta unità di elaborazione centrale (4) le informazioni associate alle immagini acquisite e/o di ricevere informazioni relative al modello digitale tridimensionale ottenuto, nonché almeno un’unità (3) per la trasmissione, opzionalmente in modalità wireless, delle informazioni associate alle immagini acquisite da detta pluralità di elementi (2) per l’acquisizione istantanea e sincronizzata di immagini verso il dispositivo di controllo (9); viene descritto altresì un procedimento per l’acquisizione di immagini e la ricostruzione digitale tridimensionale di forme anatomiche umane.

Background: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal cancers of the gastrointestinal tract PDGFRA genes. Sporadic Multiple Primary GISTs (MPGs) are a rare entity that could occur in adult patients characterized by multiple synchronous lesions generally located in the same organ and even more rarely by metachronous neoplasms. The differential diagnosis among MPGs and disseminated disease or recurrent primary GIST is critical as it affects clinical management. Case report: Here, we present a case of an 86-year-old female who underwent emergency surgery in June 2016 for a giant GIST of the stomach occupying most of the left side of the abdomen. After two years, during adjuvant imatinib 400 mg daily, emergency sigmoid resection was performed due to subacute obstruction and a colonic GIST carrying the same KIT mutation (deletion 557-558 at exon 11) of the previous gastric neoplasm was detected. In this case, we hypothesized the primary nature of the two tumors despite being metachronous and occurring in different organs. However, the same mutational pattern suggested a clonal relationship between the two neoplasms. The onset of a third duodenal lesion, that could corroborate the assumption of the primary metachronous nature of the disease, still remains an unsolved question since its malignancy was not confirmed. Conclusion: Differentiating among metachronous multiple primary GISTs or relapse on imatinib is relevant for staging and choosing the most proper therapeutic approach. Further investigations are surely needed in order to asses a diagnostic tool that may help clinicians to distinguish this rare entity (both synchronous or metachronous) from recurrences. In this scenario, molecular analysis may add essential data to discriminate sporadic MPGs and recurrent or metastatic GISTs.

Background: The nipples-saving mastectomy (NSM), most recent technique, allows the whole mammary gland removal preserving the nipple-areola compound (NAC), obtaining oncologic safe results. When indicated, NSM is validated by the great aesthetic results obtained. Objectives: The objective of this review is the evaluation of the effectiveness and oncologic safety of the nipple-saving mastectomy, marking the most frequent complications. Moreover, the possibility to use the NSM procedure as prophylactic mastectomy in patients at high risk has been evaluated. Research Methods: A bibliographic research about clinical studies and previous reviews related to nipplessaving mastectomy has been conducted. No limitation about language was performed. Results: The study included 12 articles, for a total of 2859 patients and 3849 NSM. Patients candidate to NSM, either as a prophylactic or curative treatment of mammary carcinoma, must undergo a careful selection screening. Most frequently occurring surgery-related complications were necrosis and infections; though not altering the cosmetic results, that have been positively evaluated in almost all patients. Conclusion: Preservation of the areola-nipple compound seems to be oncologically safe and does not increase local recurrences, compared to the previous techniques. Moreover, it is associated with better aesthetic results and patients’ higher satisfaction.

Particular interest is now being given to the best treatment of papillary thyroid microcarcinoma (PTMC) due to its significantly increased incidence. PTMC typically shows indolent organic behavior but, in a low percentage of cases, it can express a relative aggressive behavior. Several risk factors have been shown to negatively influence the rate of regional recurrences and metastases such as tumor diameter, Romaage, sex, multifocality, capsular invasion, extracellular diffusion, lymph node metastases, histological variants, mutated Braf and incidentality. The identification of patients with aggressive PTMCs among the majority with low risk lesions is very important to plan an adequate clinical management, thus the most appropriate surgical treatment. The latter includes thyroid lobectomy and total thyroidectomy with central compartment lymphadenectomy, though several studies did not show statistically significant differences in terms of recurrence and mortality rates between the two techniques. At last, it seems crucial to better define those biological features able to improve selection making process of patients with PTMCs aiming to reserve more radical surgery to those patients carrying more aggressive clinicopathologic features and worse prognosis.

In the United States an explosive rise in the frequency of differentiated papillary thyroid cancer ( PTC) had been seen, resulting in a nearly 800% increase over the prior 35 years, according to Surveillance, Epidemiology And Results (SEER) registry data . Similar increases have been verified in Europe and Japan. Differentiated thyroid carcinoma, PTC and follicular thyroid carcinoma, are rare in children, representing 0 .5–3.0% of all childhood cancers. The incidence increases with age, and peak incidence is observed between 15 and 19 years of age . PTC is the most common hystotype comprising about 85% of all thyroid cancer. Lymph node metastasis ( LNM) occur early and often in PTC, initially located in compartment VI . They are often small, escaping the detection by the surgeon in up to 50%. The outcome of juvenile PTC was fair, but there were many recurrences. Is not recommended a prophylactic lymph node dissection (LND) in patients clinically negative for LNM, in accordance with the American Thyroid Association (ATA) guidelines for pediatric PTC.

Brain glucose metabolism is altered in sporadic Alzheimer’s disease (sAD), whose pathologies are reproduced in rodents by intracerebroventricular (icv) infusion of streptozotocin (STZ) in subdiabetogenic doses. The icv- STZ model also culminates in central cholinergic dysfunctions, which in turn are known to underlie both the sAD cognitive decline, and synaptic plasticity impairments. Considering the cognitive-enhancing potential of chronic nicotine (Nic), we investigated whether it attenuates icv- STZ-induced impairments in recognition memory and synaptic plasticity in a cognition-relevant substrate: the hippocampal CA1-medial prefrontal cortex (mPFC) pathway. Rats treated with icv-STZ were submitted to a chronic Nic regime, and were evaluated for recognition memory. We then examined long-term potentiation (LTP), paired-pulse facilitation (PPF) under urethane anesthesia, and brains were also evaluated for hippocampus-mPFC cell density. We found that Nic treatment prevents icv-STZ-induced disruptions in recognition memory and LTP. STZ did not precipitate neuronal death, while Nic alone was associated with higher neuronal density in CA1 when compared to vehicle-injected animals. Through combining behavioral, neurophysiological, and neuropathological observations into the Nic-STZ interplay, our study reinforces that cholinergic treatments are of clinical importance against earlystage Alzheimer’s disease and mild cognitive impairments