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Background: Cardiovascular diseases in the context of renal and liver transplants remain the leading cause of morbidity and mortality. Physical exercise at a moderate intensity is allowed to contrast the risk profile. Echocardiographic evaluation is essential to stratifying potential cardiotoxicity by the standard and, more recently, the deformation and dynamic study of the intracardiac vortex. This study aims to investigate the vortex echo parameters of solid-organ-transplanted subjects who are physically active compared to a control group of healthy subjects., Methods: A group of 33 transplanted subjects (16 kidneys and 17 livers) was studied via a transthoracic echocardiography exam, comprehending the myocardial deformation parameters of global longitudinal strain (GLS), twisting of the left ventricle (LV) chamber, and HyperDoppler image acquisition., Results: The subjects enrolled in this study were 50 in total: there were 33 transplanted and 17 healthy subjects. The transplanted subjects presented higher values of interventricular septum in diastole (IVSd p = 0.001), posterior wall diastolic (PWd p = 0.05), and left ventricle mass index (LVMI p = 0.029); ejection fraction (EF) was found to be higher in athletes ( p < 0.001). Transplanted subjects presented mild diastolic dysfunction, emerging only from septal E values ( p = 0.001). The 4DStrain ( p = 0.018) and GLS2c ( p = 0.017) were significantly better in the athletes. All of the geometrical and energetical vortex data were in the normal range and no significant differences were found. An interesting positive correlation was evident for the diastolic parameter, particularly the E/A ratio ( p = 0.023) and E' septal value ( p = 0.049), along with the vorticity fluctuation. This behavior was present for all subjects, particularly those that were transplanted ( p = 0.005)., Conclusions: In the vortex investigation, especially in cases of normal EF, the positive correlation of some diastolic parameters with the flow dynamic patterns corroborates this hypothesis. The HyperDoppler analysis could be helpful to detecting potential damage earlier in the diastolic time before a systolic deficiency.

Background: Pancreatoduodenectomy (PD) is recommended in fit patients with a resectable ampullary adenocarcinoma (AA). We aimed to identify predictors of five-year recurrence/survival., Methods: Data were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD patients with a confirmed head of pancreas or periampullary malignancy (June 1st, 2012-May 31st, 2015). Patients with AA who developed recurrence/died within five-years were compared to those who did not., Results: 394 patients were included and actual five-year survival was 54%. Recurrence affected 45% and the median time-to-recurrence was 14 months. Local only, local and distant, and distant only recurrence affected 34, 41 and 94 patients, respectively (site unknown: 7). Among those with recurrence, the most common sites were the liver (32%), local lymph nodes (14%) and lung/pleura (13%). Following multivariable tests, number of resected nodes, histological T stage > II, lymphatic invasion, perineural invasion (PNI), peripancreatic fat invasion (PPFI) and ≥1 positive resection margin correlated with increased recurrence and reduced survival. Furthermore, ≥1 positive margin, PPFI and PNI were all associated with reduced time-to-recurrence., Conclusions: This multicentre retrospective study of PD outcomes identified numerous histopathological predictors of AA recurrence. Patients with these high-risk features might benefit from adjuvant therapy., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Individuals with pathologic conditions and restorative deficiencies might benefit from a combinatorial approach encompassing stem cells and dental implants; however, due to the various surface textures and coatings, the influence of titanium dental implants on cells exhibits extensive, wide variations. Three-dimensional (3D) cultures of stem cells on whole dental implants are superior in testing implant properties and were used to examine their capabilities thoroughly., Materials and Methods: The surface micro-topography of five titanium dental implants manufactured by sandblasting with titanium, aluminum, corundum, or laser sintered and laser machined was compared in this study. After characterization, including particle size distribution and roughness, the adhesion, proliferation, and viability of adipose-derived stem cells (ADSCs) cultured on the whole-body implants were tested at three time points (one to seven days). Finally, the capacity of the implant to induce ADSCs' spontaneous osteoblastic differentiation was examined at the same time points, assessing the gene expression of collagen type 1 ( coll-I ), osteonectin ( osn ), alkaline phosphatase ( alp ), and osteocalcin ( osc )., Results: Laser-treated (Laser Mach and Laser Sint) implants exhibited the highest adhesion degree; however, limited proliferation was observed, except for Laser Sint implants, while viability differences were seen throughout the three time points, except for Ti Blast implants. Sandblasted surfaces (Al Blast, Cor Blast, and Ti Blast) outpaced the laser-treated ones, inducing higher amounts of coll - I , osn , and alp , but not osc . Among the sandblasted surfaces, Ti Blast showed moderate roughness and the highest superficial texture density, favoring the most significant spontaneous differentiation relative to all the other implant surfaces., Conclusions: The results indicate that 3D cultures of stem cells on whole-body titanium dental implants is a practical and physiologically appropriate way to test the biological characteristics of the implants, revealing peculiar differences in ADSCs' adhesion, proliferation, and activity toward osteogenic commitment in the absence of specific osteoinductive cues. In addition, the 3D method would allow researchers to test various implant surfaces more thoroughly. Integrating with preconditioned stem cells would inspire a more substantial combinatorial approach to promote a quicker recovery for patients with restorative impairments.

Background: Pancreatoduodenectomy is still hampered by significant morbidity. So far, there is no universally accepted technique aimed at minimizing postoperative complications. Herein, we compare three different reconstruction techniques., Methods: This is a retrospective study of a prospectively maintained database including 283 patients operated between January 2010 and December 2020. Three reconstruction techniques were compared: (1) the Neuhaus-style telescope pancreatojejunostomy, (2) the pancreatogastrostomy, and (3) the modified Blumgart-style, duct-to-mucosa pancreatojejunostomy. The primary endpoint consisted in determining the rates of clinically relevant postoperative pancreatic fistulas (CR-POPF); the secondary endpoints included 90 days morbidity and mortality rates. A propensity score matching analysis was used., Results: Rates of CR-POPF did not differ significantly between the groups (Neuhaus-style pancreatojejunostomy 16%, pancreatogastrostomy 17%, modified Blumgart-style pancreatojejunostomy 15%), neither in the unmatched nor in the matched analysis ( p = 0.993 and p = 0.901, respectively). Similarly, no significant differences could be observed with regard to major morbidity (unmatched p = 0.596, matched p = 0.188) and mortality rates (unmatched p = 0.371, matched p = 0.209) within the first 90 days following surgery. Propensity-score matching analyses revealed, however, a higher occurrence of post-pancreatectomy hemorrhage after pancreatogastrostomy ( p = 0.015)., Conclusion: Similar CR-POPF rates suggest no crucial role of the applied reconstruction technique. Increased incidence of intraluminal post-pancreatectomy hemorrhages following pancreatogastrostomy demands awareness for meticulous hemostasis.

Enzymes are more selective and efficient than synthetic catalysts but are limited by difficult recycling. This is overcome by immobilisation, namely through encapsulation, with the main drawback of this method being slow diffusion of products and reactants, resulting in effectively lowered enzyme activity. Fluorinated dendritic amphiphiles were reported to self-assemble into regularly perforated bilayer vesicles, so-called "stomatosomes". It was proposed that they could be promising novel reaction vessels due to their increased porosity while retaining larger biomolecules at the same time. Amphiphiles were synthesised and their aggregation was analysed by cryogenic transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS) in buffered conditions necessary for enzyme encapsulation. Urease and albumin were encapsulated using the thin-film hydration method and investigated by confocal and time-gated stimulated emission depletion microscopy (gSTED). Their release was then used to probe the selective retention of cargo by stomatosomes. Free and encapsulated enzyme activity were compared and their capacity to be reused was evaluated using the Berthelot method. Urease was successfully encapsulated, did not leak out at room temperature, and showed better activity in perforated vesicles than in closed vesicles without perforations. Encapsulated enzyme could be reused with retained activity over 8 cycles using centrifugation, while free enzyme had to be filtrated. These results show that stomatosomes may be used in enzyme immobilisation applications and present advantages over closed vesicles or free enzyme.

Long-term results following solid organ transplantation do not mirror the excellent short-term results achieved in recent decades. It is therefore clear that current immunosuppressive maintenance protocols primarily addressing the adaptive immune system no longer meet the required clinical need. Identification of novel targets addressing this shortcoming is urgently needed. There is a growing interest in better understanding the role of the innate immune system in this context. In this review, we focus on macrophages, which are known to prominently infiltrate allografts and, during allograft rejection, to be involved in the surge of the adaptive immune response by expression of pro-inflammatory cytokines and direct cytotoxicity. However, this active participation is janus-faced and unspecific targeting of macrophages may not consider the different subtypes involved. Under this premise, we give an overview on macrophages, including their origins, plasticity, and important markers. We then briefly describe their role in acute allograft rejection, which ranges from sustaining injury to promoting tolerance, as well as the impact of maintenance immunosuppressants on macrophages. Finally, we discuss the observed immunosuppressive role of the vitamin-like compound tetrahydrobiopterin and the recent findings that suggest the innate immune system, particularly macrophages, as its target.

Background: The European registry for minimally invasive pancreatic surgery (E-MIPS) collects data on laparoscopic and robotic MIPS in low- and high-volume centers across Europe., Methods: Analysis of the first year (2019) of the E-MIPS registry, including minimally invasive distal pancreatectomy (MIDP) and minimally invasive pancreatoduodenectomy (MIPD). Primary outcome was 90-day mortality., Results: Overall, 959 patients from 54 centers in 15 countries were included, 558 patients underwent MIDP and 401 patients MIPD. Median volume of MIDP was 10 (7-20) and 9 (2-20) for MIPD. Median use of MIDP was 56.0% (IQR 39.0-77.3%) and median use of MIPD 27.7% (IQR 9.7-45.3%). MIDP was mostly performed laparoscopic (401/558, 71.9%) and MIPD mostly robotic (234/401, 58.3%). MIPD was performed in 50/54 (89.3%) centers, of which 15/50 (30.0%) performed ≥20 MIPD annually. This was 30/54 (55.6%) centers and 13/30 (43%) centers for MIPD respectively. Conversion rate was 10.9% for MIDP and 8.4% for MIPD. Overall 90 day mortality was 1.1% (n = 6) for MIDP and 3.7% (n = 15) for MIPD., Conclusion: Within the E-MIPS registry, MIDP is performed in about half of all patients, mostly using laparoscopy. MIPD is performed in about a quarter of patients, slightly more often using the robotic approach. A minority of centers met the Miami guideline volume criteria for MIPD., (Copyright © 2022. Published by Elsevier Ltd.)

A positive crossmatch (XM+) is considered a contraindication to solid abdominal organ transplantation except liver transplantation (LT). Conflicting reports exist regarding the effects of XM+ on post-transplant outcomes. The goal of this retrospective single-center analysis is to evaluate the influence of XM+ on relevant outcome parameters such as survival, graft rejection, biliary and arterial complications. Forty-nine adult patients undergoing LT with a XM+ between 2002 and 2017 were included. XM+ LT recipients were matched 1:2 with crossmatch negative (XM-) LT recipients based on the balance of risk (BAR) score. Patient and graft survival were compared using Kaplan-Meier survival analysis and the log-rank test. Comparative analysis of clinical outcomes in XM+ and XM- groups were conducted. Patient and graft survival were similar in XM+ and XM- patients. Rejection episodes did not differ either. Recipients with a strong XM+ were more likely to develop a PCR+ CMV infection. A XM+ was not associated with a higher incidence of biliary or arterial complications. Donor age, cold ischemia time, PCR+ CMV infection and a rejection episode were associated with the occurrence of ischemic type biliary lesions. A XM+ has no effects on patient and graft survival or other relevant outcome parameters following LT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Krendl, Fodor, Messner, Balog, Vales, Cardini, Resch, Maglione, Margreiter, Riedmann, Ulmer, Öfner, Oberhuber, Schneeberger and Weissenbacher.)

At presynaptic active zones (AZs), conserved scaffold protein architectures control synaptic vesicle (SV) release by defining the nanoscale distribution and density of voltage-gated Ca 2+ channels (VGCCs). While AZs can potentiate SV release in the minutes range, we lack an understanding of how AZ scaffold components and VGCCs engage into potentiation. We here establish dynamic, intravital single-molecule imaging of endogenously tagged proteins at Drosophila AZs undergoing presynaptic homeostatic potentiation. During potentiation, the numbers of α1 VGCC subunit Cacophony (Cac) increased per AZ, while their mobility decreased and nanoscale distribution compacted. These dynamic Cac changes depended on the interaction between Cac channel's intracellular carboxyl terminus and the membrane-close amino-terminal region of the ELKS-family protein Bruchpilot, whose distribution compacted drastically. The Cac-ELKS/Bruchpilot interaction was also needed for sustained AZ potentiation. Our single-molecule analysis illustrates how the AZ scaffold couples to VGCC nanoscale distribution and dynamics to establish a state of sustained potentiation.

Pancreatic ductal adenocarcinoma (PDAC) is still hampered by a dismal prognosis. A better understanding of the tumor microenvironment within the pancreas and of the factors affecting its composition is of utmost importance for developing new diagnostic and treatment tools. In this context, the complement system plays a prominent role. Not only has it been shown to shape a T cell-mediated immune response, but it also directly affects proliferation and apoptosis of the tumor cells, influencing angiogenesis, metastatic spread and therapeutic resistance. This makes complement proteins appealing not only as early biomarkers of PDAC development, but also as therapeutic targets. Fungal dysbiosis is currently the new kid on the block in tumorigenesis with cancer-associated mycobiomes extracted from several cancer types. For PDAC, colonization with the yeast Malassezia seems to promote cancer progression, already in precursor lesions. One responsible mechanism appears to be complement activation via the lectin pathway. In the present article, we review the role of the complement system in tumorigenesis, presenting observations that propose it as the missing link between fungal dysbiosis and PDAC development. We also present the results of a small pilot study supporting the crucial interplay between the complement system and Malassezia colonization in PDAC pathogenesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may present with a wide variety of symptoms, including neurological manifestations. We investigated clinical, demographic, laboratory, neurophysiological and imaging characteristics of SARS-CoV-2-positive children with seizures and analyzed differences between children admitted during the periods with prevalent circulation of the Alpha/Delta and Omicron variants, respectively. Patients' characteristics were analyzed according to the presence or absence of seizures and then according to the SARS-CoV-2 variants. Five-hundred and four SARS-CoV-2-positive patients were included: 93 (18.4%) with seizures and 411 (81.6%) without. Patients with seizures were older, had more commonly an underlying epilepsy and had more frequently altered C-reactive protein than those without seizures. Electroencephalography was abnormal in 5/38 cases. According to the SARS-CoV-2 variant, seizures were recorded in 4.7% of the total number of hospitalized patients during the Alpha/Delta period, and in 16.9% of patients admitted during the Omicron period. During the Alpha/Delta variants, seizures were more commonly observed in patients with epilepsy compared to those observed during the Omicron period. Our findings suggest that although SARS-CoV-2 may potentially trigger seizures, they are generally not severe and do not require intensive care admission.

This study investigated the effect of low-dose aspirin in primary adult liver transplantation (LT) on acute cellular rejection (ACR) as well as arterial patency rates. The use of low-dose aspirin after LT is practiced by many transplant centers to minimize the risk of hepatic artery thrombosis (HAT), although solid recommendations do not exist. However, aspirin also possesses potent anti-inflammatory properties and might mitigate inflammatory processes after LT, such as rejection. Therefore, we hypothesized that the use of aspirin after LT has a protective effect against ACR. This is an international, multicenter cohort study of primary adult deceased donor LT. The study included 17 high-volume LT centers and covered the 3-year period from 2013 to 2015 to allow a minimum 5-year follow-up. In this cohort of 2365 patients, prophylactic antiplatelet therapy with low-dose aspirin was administered in 1436 recipients (61%). The 1-year rejection-free survival rate was 89% in the aspirin group versus 82% in the no-aspirin group (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.63-0.94; p = 0.01). The 1-year primary arterial patency rates were 99% in the aspirin group and 96% in the no-aspirin group with an HR of 0.23 (95% CI, 0.13-0.40; p < 0.001). Low-dose aspirin was associated with a lower risk of ACR and HAT after LT, especially in the first vulnerable year after transplantation. Therefore, low-dose aspirin use after primary LT should be evaluated to protect the liver graft from ACR and to maintain arterial patency., (© 2022 The Authors. Liver Transplantation published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Competing Interests: Disclosure: The authors declare no conflict of interest.

Background: Although the influence of titanium implants' micro-surface properties on titanium discs has been extensively investigated, the research has not taken into consideration their whole-body effect, which may be considered possible using a combinatorial approach., Methods: Five titanium dental implants with a similar moderate roughness and different surface textures were thoroughly characterized. The cell adhesion and proliferation were assessed after adipose-tissue-derived stem cells (ADSCs) were seeded on whole-body implants. The implants' inductive properties were assessed by evaluating the osteoblastic gene expression., Results: The surface micro-topography was analyzed, showing that hydroxyapatite (HA)-blasted and bland acid etching implants had the highest roughness and a lower number of surface particles. Cell adhesion was observed after 24 h on all the implants, with the highest score registered for the HA-blasted and bland acid etching implants. Cell proliferation was observed only on the laser-treated and double-acid-etched surfaces. The ADSCs expressed collagen type I, osteonectin, and alkaline phosphatase on all the implant surfaces, with high levels on the HA-treated surfaces, which also triggered osteocalcin expression on day seven., Conclusions: The findings of this study show that the morphology and treatment of whole titanium dental implants, primarily HA-treated and bland acid etching implants, impact the adherence and activity of ADSCs in osteogenic differentiation in the absence of specific osteo-inductive signals.

Multisystem inflammatory syndrome in children (MIS-C) is a rare, severe complication of COVID-19. A better knowledge of immunological, cellular, and genetic characteristics of MIS-C could help better understand the pathogenesis of the disease and contribute to identifying specific diagnostic biomarkers and develop targeted therapies. We studied 37 MIS-C children at hospital admission and 24 healthy controls analyzing serum cytokines (IFN-α, IFN-β, IFN-γ, IL-6, IL-10, IL-17A, IL-12p70 and TNF), lymphocyte populations by flow cytometry and 386 genes related to autoimmune diseases, autoinflammation and primary immunodeficiencies by NGS. MIS-C patients showed a significant increase of serum IFNγ (despite a significant reduction of activated Th1) and ILs, even if with a great heterogeneity among patients, revealing different pathways involved in MIS-C pathogenesis and suggesting that serum cytokines at admission may help to select the inflammatory pathways to target in each patient. Flow cytometry demonstrated a relevant reduction of T populations while the percentage of B cell was increased in agreement with an autoimmune pathogenesis of MIS-C. Genetic analysis identified variants in 34 genes and 83.3% of patients had at least one gene variant. Among these, 9 were mutated in more patients. Most genes are related to autoimmune diseases like ATM , NCF1 , MCM4 , FCN3 , and DOCK8 or to autoinflammatory diseases associated to the release of IFNγ like PRF1 , NOD2 , and MEF . Thus, an incomplete clearance of the Sars-CoV2 during the acute phase may induce tissue damage and self-antigen exposure and genetic variants can predispose to hyper-reactive immune dysregulation events of MIS-C-syndrome. Type II IFN activation and cytokine responses (mainly IL-6 and IL-10) may cause a cytokine storm in some patients with a more severe acute phase of the disease, lymphopenia and multisystemic organ involvement. The timely identification of such patients with an immunocytometric panel might be critical for targeted therapeutic management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gelzo, Castaldo, Giannattasio, Scalia, Raia, Esposito, Maglione, Muzzica, D’Anna, Grieco, Tipo, La Cava and Castaldo.)

Several reports highlighted how public health measures aimed at limiting severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) circulation have likely contributed to reducing the circulation of other respiratory viruses, particularly during the first year of the COVID-19 pandemic. We evaluated the epidemiology of acute respiratory infections in a large cohort of hospitalized children during the third year of the pandemic (2021−2022). We retrospectively analyzed data from the health records of children (<14 years) hospitalized for acute respiratory infections between 1 July 2021 and 31 March 2022. A total of 1763 respiratory panels were collected. Overall, 1269 (72%) panels hadpositive results for at least one pathogen. Most positive panels (53.8%) belonged to patients aged 1−12 months. The most detected pathogen was respiratory syncytial virus (RSV) (57.8% of positive panels). The RSV peak occurred in November 2021. Nine hundred and forty-five (74.5%) panels were positive for one pathogen while three hundred and twenty-four (25.5%) showed multiple infections. Patients with multiple infections were significantly older than those with a single infection. The 2021−2022 peak of RSV infection in Italy occurred earlier than in the previous pre-pandemic seasons. A high number of children have been hospitalized because of acute viral infections also due to less aggressive viruses.

Endothelial hyperinflammation and vasculitis are known hallmarks of acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C). They are due to the direct effect of the virus on endothelial cells enhanced by pro-inflammatory modulators and may cause venous/arterial thrombosis. Therefore, it is essential to identify patients with endothelial damage early in order to establish specific therapies. We studied the monocyte chemoattractant protein 1 (MCP-1), the perinuclear anti-neutrophil cytoplasmic antibodies (pANCA), and the vascular endothelial growth factor A (VEGF-A) in serum from 45 MIS-C patients at hospital admission and 24 healthy controls (HC). For 13/45 MIS-C patients, we measured the three serum biomarkers also after one week from hospitalization. At admission, MIS-C patients had significantly higher levels of MCP-1 and VEGF-A than the HC, but no significant differences were observed for pANCA. While after one week, MCP-1 was significantly lower, pANCA was higher and VEGF-A levels were not significantly different from the admission values. These findings suggest an involvement of epithelium in MIS-C with an acute phase, showing high MCP-1 and VEGF-A, followed by an increase in pANCA that suggests a vasculitis development. The serum biomarker levels may help to drive personalized therapies in these phases with anticoagulant prophylaxis, immunomodulators, and/or anti-angiogenic drugs.

Normothermic machine perfusion (NMP) allows for ex vivo viability and functional assessment prior to liver transplantation (LT). Hyperspectral imaging represents a suitable, non-invasive method to evaluate tissue morphology and organ perfusion during NMP. Liver allografts were subjected to NMP prior to LT. Serial image acquisition of oxygen saturation levels (StO2), organ hemoglobin (THI), near-infrared perfusion (NIR) and tissue water indices (TWI) through hyperspectral imaging was performed during static cold storage, at 1h, 6h, 12h and at the end of NMP. The readouts were correlated with perfusate parameters at equivalent time points. Twenty-one deceased donor livers were included in the study. Seven (33.0%) were discarded due to poor organ function during NMP. StO2 ( p < 0.001), THI ( p < 0.001) and NIR ( p = 0.002) significantly augmented, from static cold storage (pre-NMP) to NMP end, while TWI dropped ( p = 0.005) during the observational period. At 12-24h, a significantly higher hemoglobin concentration (THI) in the superficial tissue layers was seen in discarded, compared to transplanted livers ( p = 0.036). Lactate values at 12h NMP correlated negatively with NIR perfusion index between 12 and 24h NMP and with the delta NIR perfusion index between 1 and 24h (rs = -0.883, p = 0.008 for both). Furthermore, NIR and TWI correlated with lactate clearance and pH. This study provides first evidence of feasibility of hyperspectral imaging as a potentially helpful contact-free organ viability assessment tool during liver NMP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fodor, Lanser, Hofmann, Otarashvili, Pühringer, Cardini, Oberhuber, Resch, Weissenbacher, Maglione, Margreiter, Zelger, Pallua, Öfner, Sucher, Hautz and Schneeberger.)

Alzheimer's disease (AD) is the most common form of dementia with millions of people affected worldwide. Pathophysiological manifestations of AD include the extracellular accumulation of amyloid beta (Abeta) pep-tides, products of the proteolytic cleavage of the amy-loid precursor protein APP. Increasing evidence sug-gests that Abeta peptides also accumulate intracellular-ly, triggering neurotoxic events such as mitochondrial dysfunction. However, the molecular factors driving formation and toxicity of intracellular Abeta are poorly understood. In our recent study [EMBO Mol Med 2022 - e13952], we used different eukaryotic model systems to identify such factors. Based on a genetic screen in yeast and subsequent molecular analyses, we found that both the yeast chaperone Ydj1 and its human ortholog DnaJA1 physically interact with Abeta, facili-tate the aggregation of Abeta peptides into small oli-gomers and promote their translocation to mitochon-dria. Deletion or downregulation of this chaperone pro-tected from Abeta-mediated toxicity in yeast and Dro-sophila AD models, respectively. Most importantly, the identified chaperone is found to be dysregulated in post-mortem human samples of AD patients. Here, we aim to outline our key findings, highlighting pathological functions of a heat shock protein (Hsp) family member, which are generally considered protective rather than toxic during neurodegeneration. Our results thus chal-lenge the concept of developing generalized chaperone activation-based therapies and call for carefully consid-ering also maladaptive functions of specific heat shock proteins., Competing Interests: Conflict of Interest: Authors declare no conflict of interest., (Copyright: © 2022 Tadic et al.)

Amyloid beta 42 (Abeta42) is the principal trigger of neurodegeneration during Alzheimer's disease (AD). However, the etiology of its noxious cellular effects remains elusive. In a combinatory genetic and proteomic approach using a yeast model to study aspects of intracellular Abeta42 toxicity, we here identify the HSP40 family member Ydj1, the yeast orthologue of human DnaJA1, as a crucial factor in Abeta42-mediated cell death. We demonstrate that Ydj1/DnaJA1 physically interacts with Abeta42 (in yeast and mouse), stabilizes Abeta42 oligomers, and mediates their translocation to mitochondria. Consequently, deletion of YDJ1 strongly reduces co-purification of Abeta42 with mitochondria and prevents Abeta42-induced mitochondria-dependent cell death. Consistently, purified DnaJ chaperone delays Abeta42 fibrillization in vitro, and heterologous expression of human DnaJA1 induces formation of Abeta42 oligomers and their deleterious translocation to mitochondria in vivo. Finally, downregulation of the Ydj1 fly homologue, Droj2, improves stress resistance, mitochondrial morphology, and memory performance in a Drosophila melanogaster AD model. These data reveal an unexpected and detrimental role for specific HSP40s in promoting hallmarks of Abeta42 toxicity., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Liver and pancreatic involvement in children with Multisystem Inflammatory Syndrome related to SARS-CoV-2 (MIS-C) has been poorly investigated so far. We reviewed a cohort of MIS-C patients to analyze the prevalence of acute liver injury (ALI) and pancreatic injury and their correlation with clinical outcomes. Demographic, clinical, laboratory and imaging features of children with MIS-C at admission and during hospital stay were prospectively collected. Fifty-five patients (mean age 6.5 ± 3.7 years) were included. At admission, 16 patients showed ALI and 5 had increased total serum lipase. During observation, 10 more patients developed ALI and 19 more subjects presented raised pancreatic enzymes. In comparison to those with normal ALT, subjects with ALI were significantly older ( p = 0.0004), whereas pancreatic involvement was associated to a longer duration of hospital stay compared with patients with normal pancreatic enzymes ( p = 0.004). Time between hospital admission and onset of ALI was shorter compared to the onset of raised pancreatic enzymes (3.2 ± 3.9 versus 5.3 ± 2.7 days, respectively; p = 0.035). Abdominal ultrasound showed liver steatosis in 3/26 (12%) and hepatomegaly in 6/26 (16%) patients with ALI; 2 patients presented enlarged pancreas. Although liver and pancreatic involvement is commonly observed in MIS-C patients, it is mild in most cases with a complete recovery.

Background: HyperDoppler is a new echocardiographic color Doppler-based technique that can assess intracardiac flow dynamics. The aim of this study was to verify the feasibility and reproducibility of this technique in unselected patients and its capability to differentiate measures of vortex flow within the left ventricle (LV) in normal sedentary subjects, athletes, and patients with heart failure. Methods: Two hundred unselected, consecutive patients presenting at the echocardiographic laboratory, 50 normal subjects, 30 athletes, and 50 patients with chronic heart failure and LV ejection fraction <50% were enrolled. Images were acquired using a MyLab X8 echo-scanner. Area, intensity, depth, length, and kinetic energy dissipation (KED) of vortex flow were measured. Results: The HyperDoppler technique feasibility was 94.5%. According to the intraclass correlation coefficient evaluations, repeatability and reproducibility of vortex flow measures were good for vortex area (0.82, 0.85), length (0.83, 0.82), and depth (0.87, 0.84) and excellent for intensity (0.92, 0.90) and KED (0.98, 0.98). Combining different vortex flow measures, the LV flow profile of healthy sedentary individuals, athletes, and heart failure patients could be differentiated. Conclusions: HyperDoppler is a feasible, reliable, and practical technique for the assessment of LV flow dynamics and may distinguish normal subjects and patients with heart failure.

The aim of this study was to determine if the risk of neurological injury to the inferior alveolar nerve (IAN) and the lingual nerve (LN) following the extraction of lower third molars is affected by the anesthetic modality (local anesthesia (LA) vs. general anesthesia (GA)). A systematic search was performed through the PubMed, Scopus, Cochrane Library, and Web of Science databases; furthermore, a manual search was performed by analyzing the references of full-text articles. From a total of 309 studies (collected after the removal of duplicates), 6 studies were selected. Of these, 4 reported a correlation between GA and nerve damage, while the other 2 did not show an obvious association. The level of bias in the studies was also calculated. Only 2 studies showed a medium risk of bias, while 4 studies showed a high risk of bias; no study showed a low risk of bias. Four of the 6 studies highlighted a higher incidence of IAN and LN injury following the extractions performed under GA. Although no scientific evidence is yet available, due to the scarcity and the limited quality of the studies in the literature, considering the risk–benefit ratio, LA should be the first choice in lower third molar surgery.

Background: Normothermic machine perfusion (NMP) has become a clinically established tool to preserve livers in a near-physiological environment. However, little is known about the predictive value of perfusate parameters toward the outcomes after transplantation., Methods: Fifty-five consecutive NMP livers between 2018 and 2019 were included. All of the livers were perfused on the OrganOx metra device according to an institutional protocol. Transplant and perfusion data were collected prospectively., Results: Forty-five livers were transplanted after NMP. Five livers stem from donors after circulatory death and 31 (68.9%) from extended criteria donors. Mean (SD) cold ischemia time was 6.4 (2.3) h; mean (SD) total preservation time was 21.4 (7.1) h. Early allograft dysfunction (EAD) occurred in 13 of 45 (28.9%) patients. Perfusate aspartate aminotransferase (P = 0.008), alanine aminotransferase (P = 0.006), lactate dehydrogenase (P = 0.007) and their development over time, alkaline phosphatase (P = 0.013), and sodium (P = 0.016) correlated with EAD. Number of perfusate platelets correlated with cold ischemia time duration and were indicative for the occurrence of EAD. Moreover, von Willebrand Factor antigen was significantly higher in perfusates of EAD livers (P < 0.001), and Δ von Willebrand factor antigen correlated with EAD. Although perfusate lactate and glucose had no predictive value, EAD was more likely to occur in livers with lower perfusate pH (P = 0.008). ΔPerfusate alkaline phosphatase, Δperfusate aspartate aminotransferase, Δperfusate alanine aminotransferase, and Δperfusate lactate dehydrogenase correlated closely with model for early allograft function but not liver graft assessment following transplantation risk score. Bile parameters correlated with extended criteria donor and donor risk index., Conclusions: Biomarker assessment during NMP may help to predict EAD after liver transplantation. The increase of transaminases and lactate dehydrogenase over time as well as platelets and vWF antigen are important factors indicative for EAD., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Despite the high prevalence of ischemic heart diseases worldwide, no antibody-based treatment currently exists. Starting from the evidence that a specific isoform of the Bone Morphogenetic Protein 1 (BMP1.3) is particularly elevated in both patients and animal models of myocardial infarction, here we assess whether its inhibition by a specific monoclonal antibody reduces cardiac fibrosis. We find that this treatment reduces collagen deposition and cross-linking, paralleled by enhanced cardiomyocyte survival, both in vivo and in primary cultures of cardiac cells. Mechanistically, we show that the anti-BMP1.3 monoclonal antibody inhibits Transforming Growth Factor β pathway, thus reducing myofibroblast activation and inducing cardioprotection through BMP5. Collectively, these data support the therapeutic use of anti-BMP1.3 antibodies to prevent cardiomyocyte apoptosis, reduce collagen deposition and preserve cardiac function after ischemia., (© 2022. The Author(s).)

Background: The pathogenesis of the novel described multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) is still debated as it is not clear if they are the same or different nosological entities. However, for both the diseases a rapid and unequivocal diagnosis is mandatory to start the therapy before the onset of severe complications. In this study, we aimed to evaluate the white cell populations in MIS-C and KD as potential markers to discriminate between the two diseases., Methods: We studied white cell populations by flow cytometry in 46 MIS-C and 28 KD patients in comparison to 70 age-matched healthy children., Results: MIS-C patients had a significant lymphopenia that involved both B and T populations while KD patients showed a significant neutrophilia and thrombocythemia. Granulocyte/lymphocyte ratio helped to diagnose both MIS-C and KD with a high diagnostic sensitivity, while a multivariate analysis of granulocyte and T lymphocyte number contributed to discriminate between the two diseases., Conclusions: The relevant lymphopenia observed in MIS-C patients suggests that the disease would be a post-infectious sequel of COVID-19 immunologically amplified by a massive cytokine release, while the significant neutrophilia and thrombocythemia observed in KD confirmed that the disorder has the genesis of a systemic vasculitis. The analysis of a panel of circulating cells may help to early diagnose and to discriminate between the two diseases., Supplementary Information: The online version contains supplementary material available at 10.1186/s41231-022-00128-2., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2022.)

Objective: Fertility loss due to cancer treatment can be a devastating experience for women and the couple. Undergoing fertility preservation can be a complex decision from both a medical and emotional point of view. The aim of the present study was to evaluate which socio-demographic and psychological factors predict a high motivation to undergo fertility preservation. Methods: Fifty-eight female cancer patients who accessed an Oncofertility Unit completed: a questionnaire to collect socio-demographic characteristics and the level of motivation, the Beck-Depression Inventory-II, the State-Trait Anxiety Inventory-Y, and the Fertility Problem Inventory. Results: Almost half of the sample (44.8%) declared a high motivation. At multiple logistic regression analysis only the "Need for parenthood" subscale of the FPI predicted a high motivation. We alternatively evaluated as possible predictor the construct "Representations about the importance of parenthood" (i.e., the sum of the "Need for Parenthood" and "Rejection of childfree lifestyle" subscales) in place of the two separate subscales. At multiple logistic regression analysis, only this variable predicted a high motivation to undergo fertility preservation. Conclusion: The most important predictor of a high motivation to undergo fertility preservation is the individual desire for parenthood. This implies that, regardless of socio-demographic characteristics, any woman of childbearing age should receive an appropriate counseling about fertility preservation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Di Mattei, Perego, Taranto, Rancoita, Maglione, Notarianni, Mangili, Bergamini, Cioffi, Papaleo and Candiani.)

Objective: The aims of the present study were to identify independent risk factors for conduit occlusion, compare outcomes of different AC placement sites, and investigate whether postoperative platelet antiaggregation is protective., Background: Arterial conduits (AC) in liver transplantation (LT) offer an effective rescue option when regular arterial graft revascularization is not feasible. However, the role of the conduit placement site and postoperative antiaggregation is insufficiently answered in the literature., Study Design: This is an international, multicenter cohort study of adult deceased donor LT requiring AC. The study included 14 LT centers and covered the period from January 2007 to December 2016. Primary endpoint was arterial occlusion/patency. Secondary endpoints included intra- and perioperative outcomes and graft and patient survival., Results: The cohort was composed of 565 LT. Infrarenal aortic placement was performed in 77% of ACs whereas supraceliac placement in 20%. Early occlusion (≤30 days) occurred in 8% of cases. Primary patency was equivalent for supraceliac, infrarenal, and iliac conduits. Multivariate analysis identified donor age >40 years, coronary artery bypass, and no aspirin after LT as independent risk factors for early occlusion. Postoperative antiaggregation regimen differed among centers and was given in 49% of cases. Graft survival was significantly superior for patients receiving aggregation inhibitors after LT., Conclusion: When AC is required for rescue graft revascularization, the conduit placement site seems to be negligible and should follow the surgeon's preference. In this high-risk group, the study supports the concept of postoperative antiaggregation in LT requiring AC., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Early graft dysfunction (EAD) complicates liver transplantation (LT). The aim of this analysis was to discriminate between the weight of each variable as for its predictive value toward patient and graft survival. Methods: We reviewed all LT performed at the Medical University of Innsbruck between 2007 and 2018. EAD was recorded when one of the following criteria was present: (i) aspartate aminotransferase (AST) levels >2,000 IU/L within the first 7 days, (ii) bilirubin levels ≥10mg/dL or (iii) international normalized ratio (INR) ≥1.6 on postoperative day 7. Results: Of 616 LT, 30.7% developed EAD. Patient survival did not differ significantly ( P = 0.092; log rank-test = 2.87), graft survival was significantly higher in non-EAD patients ( P = 0.008; log rank-test = 7.13). Bilirubin and INR on postoperative day 7 were identified as strong mortality predictors (Bilirubin HR = 1.71 [1.34, 2.16]; INR HR = 2.69 [0.51, 14.31]), in contrast to AST (HR = 0.91 [0.75, 1.10]). Similar results were achieved for graft loss estimation. A comparison with the Model for Early Allograft Function (MEAF) and the Liver Graft Assessment Following Transplantation (L-GrAFT) score identified a superior discrimination potential but lower specificity. Conclusion: Contrarily to AST, bilirubin and INR have strong predictive capacity for patient and graft survival. This fits well with the understanding, that bile duct injury and deprivation of synthetic function rather than hepatocyte injury are key factors in LT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fodor, Woerdehoff, Peter, Esser, Oberhuber, Margreiter, Maglione, Cardini, Resch, Weissenbacher, Sucher, Zoller, Tilg, Öfner and Schneeberger.)

Chronic immunosuppression is associated with an increased risk of malignancy. The main objective of this study is to evaluate the incidence and effect of post-transplant malignancies (PTMs) following pancreas transplantation. The 348 first pancreas transplants performed between 1985 and 2015 were retrospectively analyzed in this study. Incidences of PTMs, as well as patient and graft survival, were evaluated. Out of 348 patients, 71 (20.4%) developed a PTM. Median time to diagnosis was 130 months. Thirty-six patients (50.7%) developed skin cancers (four patients with melanoma, 32 with NMSCs). Solid organ malignancy occurred in 25 (35.2%), hematologic malignancy in ten patients (14.1%). Affected patients were transplanted earlier [2000 (IQR 1993-2004) vs. 2003 (IQR 1999-2008); p < 0.001]. No differences in induction therapy were seen, both groups demonstrated comparable patient and graft survival. Pancreas transplant recipients with solid organ and hematologic malignancies had a three- and six-fold increased hazard of death compared to those with skin cancers [aHR 3.04 (IQR 1.17-7.91); p = 0.023; aHR 6.07 (IQR 1.87-19.71); p = 0.003]. PTMs affect every fifth patient following pancreas transplantation. Skin cancers are the most common malignancies accounting for 50% of all PTMs. These results underscore the importance of close dermatologic follow-up.

Background: Given the susceptibility of organs to ischaemic injury, alternative preservation methods to static cold storage (SCS), such as normothermic machine perfusion (NMP) are emerging. The aim of this study was to perform a comparison between NMP and SCS in liver transplantation with particular attention to bile duct lesions., Methods: The outcomes of 59 consecutive NMP-preserved donor livers were compared in a 1 : 1 propensity score-matched fashion to SCS control livers. Postoperative complications, patient survival, graft survival and bile duct lesions were analysed., Results: While patients were matched for cold ischaemia time, the total preservation time was significantly longer in the NMP group (21 h versus 7 h, P < 0.001). Patient and graft survival rates at 1 year were 81 versus 82 per cent (P = 0.347) and 81 versus 79 per cent (P = 0.784) in the NMP and SCS groups, respectively. The postoperative complication rate was comparable (P = 0.086); 37 per cent NMP versus 34 per cent SCS patients had a Clavien-Dindo grade IIIb or above complication. There was no difference in early (30 days or less) (NMP 22 versus SCS 19 per cent, P = 0.647) and late (more than 30 days) (NMP 27 versus SCS 36 per cent, P = 0.321) biliary complications. However, NMP-preserved livers developed significantly fewer ischaemic-type bile duct lesions (NMP 3 versus SCS 14 per cent, P = 0.047)., Conclusion: The use of NMP allowed for a significantly prolonged organ preservation with a lower rate of observed ischaemic-type bile duct lesions., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: Declaration of competing interest The authors have no conflict of interest relevant to this article.

In search for novel biomarkers to assess graft quality, we investigated whether defined candidate genes are predictive for outcome after liver transplantation (LT). Zero-hour liver biopsies were obtained from 88 livers. Gene expression of selected candidate markers was analyzed and correlated with clinical parameters as well as short and long-term outcomes post LT. Whereas both, the calculated Eurotransplant Donor-Risk-Index and the donor body mass index, had either a poor or no predictive value concerning serum levels indicative for liver function (ALT, AST, GGT, bilirubin) after 6 months, chronological donor age was weakly predictive for serum bilirubin (AUC=0.67). In contrast, the major histcompatibility complex class I related chain A (MICA) mRNA expression demonstrated a high predictive value for serum liver function parameters revealing an inverse correlation (e.g. for ALT: 3 months p=0.0332; 6 months p=0.007, 12 months 0.0256, 24 months p=0.0098, 36 months, p=0.0153) and proved significant also in a multivariate regression model. Importantly, high expression of MICA mRNA revealed to be associated with prolonged graft survival (p=0.024; log rank test) after 10 years of observation, whereas low expression was associated with the occurrence of death in patients with transplant related mortality (p=0.031). Given the observed correlation with short and long-term graft function, we suggest MICA as a biomarker for pre-transplant graft evaluation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Resch, Hackl, Esser, Günther, Schwelberger, Ritschl, Ebner, Maglione, Mellitzer, Biebl, Öllinger, Zoller, Schneeberger and Kotsch.)

Background: Dysbiosis of the intestinal flora has emerged as an oncogenic contributor in different malignancies. Recent findings suggest a crucial tumor-promoting role of micro- and mycobiome alterations also in the development of pancreatic ductal adenocarcinoma (PDAC)., Methods: To summarize the current knowledge about this topic, a systematic literature search of articles published until October 2020 was performed in MEDLINE (PubMed)., Results: An increasing number of publications describe associations between bacterial and fungal species and PDAC development. Despite the high inter-individual variability of the commensal flora, some studies identify specific microbial signatures in PDAC patients, including oral commensals like Porphyromonas gingivalis and Fusobacterium nucleatum or Gram-negative bacteria like Proteobacteria . The role of Helicobacter spp. remains unclear. Recent isolation of Malassezia globosa from PDAC tissue suggest also the mycobiota as a crucial player of tumorigenesis. Based on described molecular mechanisms and interactions between the pancreatic tissue and the immune system this review proposes a model of how the micro- and the mycobial dysbiosis could contribute to tumorigenesis in PDAC., Conclusions: The presence of micro- and mycobial dysbiosis in pancreatic tumor tissue opens a fascinating perspective on PDAC oncogenesis. Further studies will pave the way for novel tumor markers and treatment strategies.

Due to the lack of suitable organs transplant surgeons have to accept unfavorable extended criteria donor (ECD) organs. Recently, we demonstrated that the perfusion of kidney organs with anti-human T-lymphocyte globulin (ATLG) prior to transplantation ameliorates ischemia-reperfusion injury (IRI). Here, we report on the results of perioperative ATLG perfusion in a randomized, single-blinded, placebo-controlled, feasibility trial (RCT) involving 30 liver recipients (LTx). Organs were randomly assigned for perfusion with ATLG/Grafalon ® (AP) ( n = 16) or saline only (control perfusion = CP) ( n = 14) prior to implantation. The primary endpoint was defined as graft function reflected by aspartate transaminase (AST) values at day 7 post-transplantation (post-tx). With respect to the primary endpoint, no significant differences in AST levels were shown in the intervention group at day 7 (AP: 53.0 ± 21.3 mg/dL, CP: 59.7 ± 59.2 mg/dL, p = 0.686). Similarly, exploratory analysis of secondary clinical outcomes (e.g., patient survival) and treatment-specific adverse events revealed no differences between the study groups. Among liver transplant recipients, pre-operative organ perfusion with ATLG did not improve short-term outcomes, compared to those who received placebo perfusion. However, ATLG perfusion of liver grafts was proven to be a safe procedure without the occurrence of relevant adverse events.

Background: Understanding the safety of vaccines is critical to inform decisions about vaccination. Our objective was to conduct a systematic review of the safety of vaccines recommended for children, adults, and pregnant women in the United States., Methods: We searched the literature in November 2020 to update a 2014 Agency for Healthcare Research and Quality review by integrating newly available data. Studies of vaccines that used a comparator and reported the presence or absence of key adverse events were eligible. Adhering to Evidence-based Practice Center methodology, we assessed the strength of evidence (SoE) for all evidence statements. The systematic review is registered in PROSPERO (CRD42020180089)., Results: Of 56,603 reviewed citations, 338 studies reported in 518 publications met inclusion criteria. For children, SoE was high for no increased risk of autism following measles, mumps, and rubella (MMR) vaccine. SoE was high for increased risk of febrile seizures with MMR. There was no evidence of increased risk of  intussusception with rotavirus vaccine at the latest follow-up (moderate SoE), nor of diabetes (high SoE). There was no evidence of increased risk or insufficient evidence for key adverse events for newer vaccines such as 9-valent human papillomavirus and meningococcal B vaccines. For adults, there was no evidence of increased risk (varied SoE) or insufficient evidence for key adverse events for the new adjuvanted inactivated influenza vaccine and recombinant adjuvanted zoster vaccine. We found no evidence of increased risk (varied SoE) for key adverse events among pregnant women following tetanus, diphtheria, and acellular pertussis vaccine, including stillbirth (moderate SoE)., Conclusions: Across a large body of research we found few associations of vaccines and serious key adverse events; however, rare events are challenging to study. Any adverse events should be weighed against the protective benefits that vaccines provide., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Synaptic plasticity is a cellular model for learning and memory. However, the expression mechanisms underlying presynaptic forms of plasticity are not well understood. Here, we investigate functional and structural correlates of presynaptic potentiation at large hippocampal mossy fiber boutons induced by the adenylyl cyclase activator forskolin. We performed 2-photon imaging of the genetically encoded glutamate sensor iGluu that revealed an increase in the surface area used for glutamate release at potentiated terminals. Time-gated stimulated emission depletion microscopy revealed no change in the coupling distance between P/Q-type calcium channels and release sites mapped by Munc13-1 cluster position. Finally, by high-pressure freezing and transmission electron microscopy analysis, we found a fast remodeling of synaptic ultrastructure at potentiated boutons: Synaptic vesicles dispersed in the terminal and accumulated at the active zones, while active zone density and synaptic complexity increased. We suggest that these rapid and early structural rearrangements might enable long-term increase in synaptic strength., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The aim was to investigate the efficacy of citric acid and ethylenediaminetetraacetic acid (EDTA)-based treatments on smear layer removal and blood clot formation and stabilization., Method and Materials: After scaling and root planing, 126 root samples were divided into seven groups treated with: deionized water; saline; citric acid solution; Ultradent Citric Acid gel; EDTA solution; EDTA-based PrefGel; or untreated. Each group was divided into three subgroups: I for the evaluation of smear layer removal and surface wettability, II and III for the evaluation of blood clot formation and stabilization in static or dynamic rinsing conditions., Results: Conditioning agent treatments increased surface wettability with respect to untreated samples (Ultradent: 45 ± 1 degrees, P = 6.2 × 10-3; EDTA: 36 ± 5 degrees, P = 8.9 × 10-7; PrefGel: 47 ± 7 degrees, P = 3.2 × 10-2). Smear layer removal (30% to 60% with respect to untreated samples) was observed for all the conditioning agents. Clot was absent on untreated samples and samples treated with deionized water. Clot quality was significantly higher for samples treated with conditioning agents (P < .05) and similar between group II and III (P > .05). A statistically significant difference (P = .027) was observed for clot coverage of the saline group, comparing static and dynamic rinsing, confirming the positive effect of treatments on clot stabilization., Conclusions: The use of conditioning agents improves smear layer removal and clot formation and stabilization with respect to scaling and root planing procedure only, which is, however, considered an essential procedure to promote wound healing in periodontal surgery.

Objectives: To assess the frequency of major complications after multi-probe stereotactic radiofrequency ablation (SRFA) in a large cohort of patients over 15 years and to elucidate risk factors for adverse events., Materials and Methods: A retrospective study was carried out between July 2003 and December 2018. Seven hundred ninety-three consecutive patients (median 65.0 years (0.3-88), 241 women and 552 men, were treated in 1235 SRFA sessions for 2475 primary and metastatic liver tumors with a median tumor size of 3.0 cm (0.5-18 cm). The frequency of major complications was evaluated according to SIR guidelines and putative predictors of adverse events analyzed using simple and multivariable logistic regression., Results: Thirty-day mortality after SRFA was 0.5% (6/1235) with an overall major complication rate of 7.4% (91/1235). The major complication rate decreased from 11.5% (36/314) (before January 2011) to 6.0% (55/921) (p = 0.001). 50.5% (46/91) of major complications were successfully treated in the same anesthetic session by angiographic coiling for hemorrhage and chest tube insertion for pneumothorax. History of bile duct surgery/intervention, number of coaxial needles, and location of tumors in segment IVa or VIII were independent prognostic factors for major complications following multivariable logistic regression analysis. Simple logistic regression revealed the number of tumors, tumor size, location close to the diaphragm, tumor conglomerate, and segment VII as other significant predictors., Conclusion: SRFA of liver tumors is safe and can extend the treatment spectrum of conventional RFA. Adaptations over time combined with increasing experience resulted in a significant decrease in complications., Key Points: • In 1235 ablation sessions in 793 patients over 15 years, we found a mortality rate of 0.5% (6/1235) and an overall major complication rate of 7.4%, which fell from 11.5 (36/314) to 6.0% (55/921, p = 0.001) after January 2011, likely due to procedural adaptations. • History of bile duct surgery/intervention (p = 0.013, OR = 3.290), number of coaxial needles (p = 0.026, OR = 1.052), and location of tumors in segment IVa (p = 0.016, OR = 1.989) or VIII (p = 0.038, OR = 1.635) were found to be independent prognostic factors. • Simple logistic regression revealed that number of tumors, tumor size, location close to the diaphragm, tumor conglomerates, and segment VII were other significant predictors of major complications.

Purpose: To assess the effects of grade IV titanium ultrasonic tip instrumentation on different grade IV titanium implant surfaces and compare the decontamination of different implant surfaces using chlorhexidine, blue laser, or ozone., Materials and Methods: Profilometry and energy-dispersive x-ray spectroscopy (EDS) analyses were performed on smooth, laser-micropatterned, and sandblasted grade IV titanium sample disks before (t 0 ) and after (t 1 ) ultrasonic instrumentation with an ultrasonic grade IV titanium tip. Samples were also incubated with a Streptococcus sanguinis culture. Each surface type was then treated with chlorhexidine, blue laser, or ozone (three test groups + control group). Scanning electron microscopy (SEM) images were taken after bacterial growth and after decontamination., Results: After ultrasonic instrumentation, surface roughness (R a ) decreased on sandblasted and micropatterned surfaces, whereas it remained substantially unvaried on the smooth surface. SEM images revealed that the laser-micropatterned structure remained substantially unvaried after instrumentation. EDS revealed a minimal quantity of carbon and iron, found in the laser-treated and sandblasted group at t0. A minimal quantity of aluminum and oxygen was found on the sandblasted surface at t 0 and t 1 . Ozone therapy achieved the highest decontaminating effect, regardless of implant surface topography., Conclusion: Among the alternative therapies to ultrasonic instrumentation with titanium tips, ozone appears to be effective regardless of the type of implant surface; it can be used for the decontamination treatment of implants without altering the surface structure.