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Purpose The incidence of inguinal hernia is higher in elderly because of aging-related diseases like prostatism, bronchitis, collagen laxity. A conservative management is common in elderly to reduce surgery-related risks, however watchful waiting can expose to obstruction and strangulation. The aim of the present study was to assess the impact of emergency surgery in a large series of elderly with complicated groin hernia and to identify the independent risk factors for postoperative morbidity and mortality. The predictive performance of prognostic risk scores has been also assessed. Methods This is a prospective observational study carried out between January 2017 and June 2018 in elderly patients who underwent emergency surgery for complicated hernia in 38 Italian hospitals. Pre-operative, surgical and postoperative data were recorded for each patient. ASA score, Charlson’s comorbidity index, P-POSSUM and CR-POSSUM were assessed. Results 259 patients were recruited, mean age was 80 years. A direct repair without mesh was performed in 62 (23.9%) patients. Explorative laparotomy was performed in 56 (21.6%) patients and bowel resection was necessary in 44 (17%). Mortality occurred in seven (2.8%) patients. Fifty-five (21.2%) patients developed complications, 12 of whom had a major one. At univariate and multivariate analyses, Charlson’s comorbidity index ≥ 6, altered mental status, and need for laparotomy were associated with major complications and mortality Conclusion Emergency surgery for complicated hernia is burdened by high morbidity and mortality in elderly patients. Preoperative comorbidity played a pivotal role in predicting complications and mortality and therefore Charlson’s comorbidity index could be adopted to select patients for elective operation

HBeAg is a marker of HBV-activity, and HBeAg-loss predicts a favorable clinical outcome. Here, we characterize HBeAg-levels across different phases of HBV infection, their correlation with virological/biochemical markers and the virological response to anti-HBV therapy. Quantitative HBeAg (qHBeAg, DiaSorin) is assessed in 101 HBeAg+ patients: 20 with acute-infection, 20 with chronic infection, 32 with chronic hepatitis and 29 with immunosuppression-driven HBV-reactivation (HBV-R). A total of 15/29 patients with HBV-R are monitored for &gt, 12 months after starting TDF/ETV. qHBeAg is higher in immunosuppression-driven HBV-R (median[IQR]:930[206–1945]PEIU/mL) and declines in chronic hepatitis (481[28–1393]PEIU/mL, p = 0.03), suggesting HBeAg production, modulated by the extent of immunological pressure. This is reinforced by the negative correlation between qHBeAg and ALT in acute infection (Rho = −0.66, p = 0.006) and chronic hepatitis (Rho = −0.35, p = 0.05). Interestingly, qHBeAg strongly and positively correlates with qHBsAg across the study groups, suggesting cccDNA as a major source of both proteins in the setting of HBeAg positivity (with limited contribution of integrated HBV-DNA to HBsAg production). Focusing on 15 patients with HBV-R starting TDF/ETV, virological suppression and HBeAg-loss are achieved in 60% and 53.3%. Notably, the combination of qHBeAg &gt, 2000 PEIU/mL + qHBsAg &gt, 52,000 IU/mL at HBV-R is the only factor predicting no HBeAg loss (HBeAg loss: 0% with vs. 72.7% without qHBeAg &gt, 52,000 IU/mL, p = 0.03). In conclusion, qHBeAg varies over the natural course of HBV infection, according to the extent of immunological pressure. In the setting of HBV-R, qHBeAg could be useful in predicting the treatment response under immunosuppression.

Background: A limited number of studies investigating perioperative risk factors associated with emergency appendectomy in elderly patients have been published to date. Whether older age may be associated with poorer outcomes following appendectomy is still a matter of debate. The primary aim of this study was to determine the predictors of postoperative morbidity following appendectomy in patients aged ≥ 65years. Methods: Data regarding all elderly patients who underwent emergency appendectomy from January 2017 to June 2018 admitted 36 Italian surgical departments were prospectively collected and analyzed. Baseline demographics and perioperative variables were evaluated. Uni- and multivariate analyses adjusted for differences between groups were carried out to determine possible predictors of adverse outcomes after appendectomy. Results: Between January 2017 and June 2018, 135 patients aged ≥ 65years with a diagnosis of AA met the study inclusion criteria. Twenty-six patients (19.3%) were diagnosed with some type of postoperative complication. Decreasing the preoperative hemoglobin level showed a statistically significant association with postoperative complications (OR 0.77, CI 0.61–0.97, P = 0.03). Preoperative creatinine level (P = 0.02, OR 2.04, CI 1.12–3.72), and open appendectomy (P = 0.03, OR 2.67, CI 1.11–6.38) were significantly associated with postoperative morbidity. After adjustment, the only independent predictor of postoperative morbidity was preoperative creatinine level (P = 0.04, OR 2.01, CI 1.05–3.89). Conclusions: In elderly patients with AA, perioperative risk assessment in the emergency setting must be as accurate as possible to identify modifiable risk factors that can be addressed before surgery, such as preoperative hemoglobin and creatinine levels.

Background The aim of this study was to investigate the impact of anti-HBc (HBcAb) positivity on the progression of liver fibrosis (Fibrosis-4 score >3.25) in the Italian cohort of HIV-infected individuals naïve to antiretroviral treatment (ICONA). Methods All patients with FIB-4 Results Patients who were HBcAb+/HCV-/HBs antigen (HBsAg)- and HCV+/HBcAb+/HBsAg- or HBsAg+/HBcAb+/HCV- had CD4+ cell counts below the nadir and significantly higher prevalence of AIDS diagnosis at baseline than the other groups (P < .0001). A Cox regression model adjusted for age, HIV transmission mode, country of birth, and alcohol consumption showed a higher relative risk (HR) of progression to FIB-4 >3.25 in HCV+/HBcAb+/HBsAg- patients (HR, 7.2; 95% CI, 3 8–13.64). Conclusions HBcAb+ contributes to liver damage in HIV+/HCV+/HBcAb+/HBsAg- subjects. A careful monitoring for signs of previous HBV infection is needed in this kind of patients.

Purpose: To assess the efficacy of radiomics features obtained by computed tomography (CT) examination as biomarkers in order to select patients with lung adenocarcinoma who would benefit from immunotherapy. Methods: Seventy-four patients (median age 63 years, range 42–86 years) with histologically confirmed lung cancer who underwent immunotherapy as first- or second-line therapy and who had baseline CT studies were enrolled in this approved retrospective study. As a control group, we selected 50 patients (median age 66 years, range 36–86 years) from 2005 to 2013 with histologically confirmed lung adenocarcinoma who underwent chemotherapy alone or in combination with targeted therapy. A total of 573 radiomic metrics were extracted: 14 features based on Hounsfield unit values specific for lung CT images, 66 first-order profile features based on intensity values, 43 second-order profile features based on lesion shape, 393 third-order profile features, and 57 features with higher-order profiles. Univariate and multivariate statistical analysis with pattern recognition approaches and the least absolute shrinkage and selection operator (LASSO) method were used to assess the capability of extracted radiomics features to predict overall survival (OS) and progression free survival (PFS) time. Results: A total of 38 patients (median age 61, range 41–78 years) with confirmed lung adenocarcinoma and subjected to immunotherapy satisfied inclusion criteria, and 50 patients in a control group were included in the analysis The shift in the center of mass of the lesion due to image intensity was significant both to predict OS in patients subjected to immunotherapy and to predict PFS in patients subjected to immunotherapy and in patients in the control group. With univariate analysis, low diagnostic accuracy was reached to stratify patients based on OS and PFS time. Regarding multivariate analysis, considering the robust (two morphological features, three textural features and three higher-order statistical metrics) application of the LASSO approach and all patients, a support vector machine reached the best results for stratifying patients based on OS (area under curve (AUC) of 0.89 and accuracy of 81.6%). Alternatively, considering the robust predictors (six textural features and one higher-order statistical metric) and application of the LASSO approach including all patients, a decision tree reached the best results for stratifying patients based on PFS time (AUC of 0.96 and accuracy of 94.7%). Conclusions: Specific radiomic features could be used to select patients with lung adenocarcinoma who would benefit from immunotherapy because a subset of imaging radiomic features useful to predict OS or PFS time were different between the control group and the immunotherapy group.

The role of novel HBV markers in predicting Hepatitis B virus reactivation (HBV-R) in HBsAg-negative/anti-HBc-positive oncohaematological patients was examined. One hundred and seven HBsAg-negative/anti-HBc-positive oncohaematological patients, receiving anti-HBV prophylaxis for > 18 months were included. At baseline, all patients had undetectable HBV DNA, and 67.3% were anti-HBs positive. HBV-R occurred in 17 (15.9%) patients: 6 during and 11 after the prophylaxis period. At HBV-R, the median (IQR) HBV-DNA was 44 (27–40509) IU/ml, and the alanine aminotransferase upper limit of normal (ULN) was 44% (median [IQR]: 81[49–541] U/L). An anti-HBc>3 cut-off index (COI) plus anti-HBs persistently/declining to 2 time points, also predicts HBV-R (OR [95% CI ]: 13.8 [3.6–52.6]; 50% of positive vs. 7% of negative patients to these markers experienced HBV-R, P=0.001).HS-HBs and anti-HBc titration proved useful early markers of HBV-R.The use of these markers demonstrated that HBV-R frequently occurs in oncohaematological patients with signs of resolved HBV infection, raising issues of proper HBV-R monitoring.

Background Our study gives a clear result about sealants treatment in preventing dental caries manifestation and reducing its prevalence in children aged 6–11 years old. Aim and objective This study aims to compare and evaluate the progress of dental caries in the first and second permanent molars and also to evaluate, within a period of 24 months, the clinical effects of dental sealants, used in the treatment of occlusive cavities, among children 6–11 years old. Materials and methods Participants: The overall sample was composed of 120 children, to whom we randomly chose 480 posterior teeth, which were divided into two groups. Intervention: The first group was the control group with 240 untreated teeth, while the second group had an equal number of teeth, which underwent the sealant treatment. The study participants were evaluated within the periods 0, 6, 12, 18, and 24 months. The study participants were checked every 6 months. Basic design: This observational, analytical, and descriptive research was designed as a longitudinal study. The study started in January 2019 and ended in January 2020. The study was conducted in five dental clinics in the city of Vlore, Albania. Results After 24 months of observation, we noticed that the number of dental caries in the untreated group is three times higher than the number of dental caries in the treated group. In the group of teeth treated with sealant, 189 (78.8%) teeth remained unaffected by dental caries. The present study showed that there is a significant correlation between period and caries manifestation (p < 0.05). It also proved that sealant treatment is an important measure and it is highly significant in the caries reduction (p = 0.000). Conclusion This study proved that sealant treatment is highly successful in reducing dental caries. In the future, it is worthwhile to go further in this research. Clinical significance Dental caries is a problem in children aged 6–11 years old and not only. That is why this study recommends that sealants treatment should be used to prevent and reduce the prevalence of dental caries. How to cite this article Canga M, Malagnino G, Malagnino VA, et al. Effectiveness of Sealants Treatment in Permanent Molars: A Longitudinal Study. Int J Clin Pediatr Dent 2021;14(1):41–45.

Background In the last two pandemic years, the Emergency Departments (ED) have been overrun with COVID-19 suspicious patients, creating a pressing need to optimize resources through risk stratification for those patients. For this reason, the assessment of prognostic tools and biomarkers have been necessary. Some dataon the role played by laboratory biomarkers in the early risk stratification of COVID-19 patients have been recently published. The aim of this study is to assess the potential role of the new biomarker mid-regional proadrenomedullim (MR-proADM) in stratifying the in-hospital mortality risk of COVID-19 patients at the triage in order to help the emergency physician in the decision-making process. A further goal of the present study is to evaluate whether MR-proADM together with other biochemical markers could play a key role in assessing the correct care level of these patients by predicting who could need intensive care and ventilation. Methods Data from 321 consecutive patients admitted to the triage of the emergency department with a COVID-19 infection were analyzed. Epidemiological, demographic, clinical, laboratory, and outcome data were assessed. C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), d-dimer and MR-proADM blood levels were also evaluated. Results All the biomarkers evaluated showed significant increased values at admission in the emergency department in non-survivorsvs survivors as well in ventilated as compared to non-ventilated patients. Moreover, all the biomarkers analyzed showed animportant role in predicting mortality, need of invasive mechanical ventilation (IMV) and non-invasive mechanical ventilation (NIMV) in patients admitted at the emergency department with COVID-19 infection as analyzed by the univariate Cox regression analysis. Pooling together both clinical and laboratory variables in a multivariate analysis, all biomarkers, except for PCT, seem to play a significant role in the mortality risk stratification at admission in the emergency department. Similarly, an increase of MR-proADM level at ED admission resulted independently associated with a threefold times higher risk of IMV. LDH showed a smaller but still significant power. CRP only showed a significant predictive value for the need of NIMV. In patients COVID-19 positive, MR-proADM assessed at the admission in the triage showed a good discriminative performance both for in-hospital mortality (AUC 0,85) and for prediction of IMV (AUC 0,81), whereas it was less effective for NIMV prediction (AUC 0,71). ROC curves and AUC resulted significantly greater for MR-proADM as compared to other laboratory biomarkers for the primary endpoint, i.e. in-hospital mortality, with the exception of CRP. Conclusion This study shows that MR-proADM seems to be particularly effective for early predicting mortality and the need of ventilation in COVID-19 patients admitted to the emergency department.

As the world population is aging rapidly, emergency abdominal surgery for acute abdomen in the elderly represents a global issue, both in developed and developing countries. Data regarding all the elderly patients who underwent emergency abdominal surgery from January 2017 to December 2017 at 36 Italian surgical departments were analyzed with the aim to appraise the contemporary reality regarding the use of emergency laparoscopy for acute abdomen in the elderly. 1993 patients were enrolled. 1369 (68.7%) patients were operated with an open technique; whereas, 624 (31.3%) underwent a laparoscopic operation. The postoperative morbidity rate was 32.6%, with a statically significant difference between the open and the laparoscopic groups (36.2% versus 22.1%, p < 0.001). The reported mortality rate was 8.8%, with a statistically significant difference between the open and the laparoscopic groups (11.2% versus 2.2%, p < 0.001). Our results demonstrated that patients in the ASA II (58.1%), ASA III (68.7%) and ASA IV (88.5%) groups were operated with the traditional open technique in most of the cases. Only a small percentage of patients underwent laparoscopy for perforated gastro-duodenal ulcer repair (18.9%), adhesiolyses with/without small bowel resection (12.2%), and large bowel resection (10.7%). Conversion to open technique was associated with a higher mortality rate (11.1% versus 2.2%, p < 0.001) and overall morbidity (38.9% versus 22.1%, p = 0.001) compared with patients who did not undergo conversion. High creatinine (p < 0.001) and glycaemia (p = 0.006) levels, low hemoglobin levels (p < 0.001), oral anticoagulation therapy (p = 0.001), acute respiratory failure (p < 0.001), presence of malignancy (p = 0.001), SIRS (p < 0.001) and open surgical approach (p < 0.001) were associated with an increased risk of postoperative morbidity. Regardless of technical progress, elderly patients undergoing emergency surgery are at very high risk for in-hospital complications. A detailed analysis of complications and mortality in the present study showed that almost 9% of elderly patients died after surgery for acute abdomen, and over 32% developed complications.

BackgroundCurrently, no data are available on the burden of morbidity and mortality in people with HIV-1 (PWH) harboring a 4-class drug-resistant (4DR) virus (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase strand transfer inhibitors). The study aimed to assess the incidence of clinical events and death in this population.MethodsThis was a cohort study on PWH from the PRESTIGIO Registry with a documented 4DR virus. Burden of disease was defined as the occurrence of any new event including an AIDS-defining event (ADE) or non-AIDS-defining event (NADE) or death from any cause after 4DR evidence (baseline). Cox regression models evaluated factors associated with the risk of new clinical events/death.ResultsAmong 148 PWH followed for a median (interquartile range) of 47 (32–84) months after 4DR evidence, 38 PWH had 62 new events or died from any cause (incidence rate, 9.12/100 person-years of follow-up; 95% CI = 6.85–11.39): 12 deaths (6 AIDS-related and 6 non-AIDS-related), 18 ADEs, 32 NADEs; 20 of the 38 NADEs (45%) of the incident clinical events were malignancies. The 4-year cumulative incidence of death was 6% (95% CI, 3%–13%), and that of ≥1 event or death was 22% (95% CI, 16%–31%). A higher risk of new clinical events/death was more likely in PWH with previous clinical events (adjusted hazard ratio [aHR], 2.67; 95% CI, 1.07–6.67) and marginally associated with lower baseline CD4+/CD8+ ratio (aHR, 0.82; 95% CI, 0.65–1.02).ConclusionsPWH harboring 4DR have a high burden of disease with a worrying incidence of malignancies, strongly advising for close prevention and monitoring interventions as well as access to innovative therapeutic strategies, especially in people with a history of clinical events and low CD4+/CD8+ ratio.

During the last decades, society has increasingly moved towards the adoption of digital solutions in almost every aspect of people's lives with the aim of enhancing daily activities. At the same time, the environmental impact of the built environment has attracted the attention of public opinion that is gradually perceiving the necessity of limiting its negative effects in order to safeguard the Earth and people's wellbeing. The Internet of Things is one of the biggest ecosystems that is bringing innovations encompassing digital solutions in almost every sector. On the other hand, the Building Information Modeling approach allows for data sharing among stakeholders, traceability, and the integrated management of the building or infrastructure life-cycle through a 3D informative virtual model. Our study reviews existing research works and technological solutions that integrate these two important topics to enhance the sustainability of the built environment, making it smarter. The presented review analyses the existing papers available in literature from January 2015 to December 2020, to present the best practices in this integration and discuss limitations of the identified solutions. Based on the outcomes of the analysis and aiming at the creation of a solid knowledge basis for the community interested in the sector, a comprehensive modular architecture has been proposed. Finally, new directions for future works are presented by discussing how the proposed architecture can actually facilitate the design and development phases.

Objectives: To determine the reproducibility of the National Comprehensive Cancer Network (NCCN) resectability status classification for pancreatic cancer. Background: The NCCN classification defines 3 resectability classes (resectable, borderline resectable, locally advanced), according to vascular invasion. It is used to recommend different approaches and stratify patients during clinical trials. Methods: Prospective, multicenter, observational study (trial ID: NCT03673423). Main outcome measure was the interobserver agreement of tumor assignment to different resectability classes and quantification of vascular invasion degrees. Agreement was measured by Fleiss' k (k = 1 perfect agreement; k = 0 agreement by chance). Sixty-nine computed tomography (CT) scans of pathologically confirmed pancreatic adenocarcinoma were independently reviewed in a blinded fashion by 22 observers from 11 hospitals (11 surgeons and 11 radiologists). Rating differences between surgeons or radiologists and between hospitals with different volumes (≥60 or 180° (k range: 0.619-0.756). Neither reviewers' specialty nor hospital volume influenced the agreement. Conclusions: There is high variability in the assignment to resectability categories, which may compromise the reliability of treatments recommendations and the evidence of trials stratifying patients in resectability classes. Criteria should be revised to allow a reproducible classification.

The research aims to assess whether the Living-Lab methodology can facilitate the introduction of new technologies within a Public Administration (PA). Previous research explored the challenges and benefits derived from the introduction of ICT into public organizations through the presentation of qualitative case studies. None of these works evaluates if, and eventually how, the introduction of new technologies in Public Administrations (PAs) can be facilitated by the Living Lab (LL). This paper attempts to close this gap by presenting the results of B@ARCA - BIM at ARCA, a research project where the development of Building Information Modelling (BIM) based methodologies and technologies and their introduction into a Public Organization has been carried out embracing the Living Lab methodology. In detail, the project objective is to equip the ARCA agency, the authority in charge of the management of the social housing asset in the Puglia Region, with innovative technological solutions useful to improve the maintenance work of the old and great heritage. The level of acceptance of the new technology, measured through quantitative questionnaires, resulted in increased after the completion of the Living Lab development activities. These initial results may encourage public administrations to use the Living Lab to expose their employees to not just BIM but also the series of new technologies needed for the digitization of the public administration.

ObjectivesTo evaluate HIV-1 tropism in 1382 combined antiretroviral therapy (cART)-experienced patients failing therapy to characterize those with exhausted therapeutic options.MethodsHIV-1 genotypic tropism was inferred through Geno2Pheno by estimating the false-positive-rate (FPR) values. Cumulative resistance and drug activity were evaluated by Stanford algorithm.ResultsOverall, median (IQR) CD4 count (cells/mm3) nadir and at last genotypic resistance test (GRT) available were 98 (33–211) and 312 (155–517), respectively. Considering HIV-1 tropism, 30.5% had X4/dual-mixed strains (FPR ≤5%: 22.2%; FPR 5%–10%: 8.3%). By stratifying according to tropism, by decreasing FPR, a significant decrease of CD4 nadir and at last GRT was observed. The proportion of individuals with CD4 count ConclusionsOur findings showed that a small proportion of cART failing individuals have limited therapeutic options. However, tropism determination might help to identify people who have accumulated a high level of resistance and have a greater risk of advanced disease.

Background Disease modifying therapies for multiple sclerosis (MS) can impair the specific immune response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Specifically, it is recognized that ocrelizumab reduces or abrogates anti-SARS-CoV-2 antibody production after natural infection or vaccination, while very little is known about T-cell responses. Methods We developed an interferon (IFN)-γ release assay (IGRA) to detect T-cell responses specific to SARS-CoV-2 after overnight stimulation of whole blood with peptide libraries covering the immunodominant sequence domains of the Spike glycoprotein (S) and the Nucleocapsid phosphoprotein (N). Results Five patients with MS receiving ocrelizumab treatment for at least 1 year and recovered from SARS-CoV-2 infection were enrolled in the study. Despite the absence or the very low concentration of anti-S antibodies, a T-cell response was detectable in all the five MS patients. These results are in accordance with the marked reduction of peripheral B-lymphocyte absolute counts induced by ocrelizumab, that, conversely, did not affect peripheral blood T-lymphocyte subset absolute and relative counts and CD4/CD8 ratio. Conclusions The detection of specific T-cell responses to SARS-CoV-2 in patients receiving B-cell depleting therapies represents a useful tool to improve the diagnostic approach in SARS-CoV-2 infection and to accurately assess the immunological response after natural infection or vaccination.

The morbidity and mortality rates of human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfection are higher than that of either infection alone. Outcomes and the virological response to antiretrovirals (combination antiretroviral therapy, cART) were explored in HIV/HBV subjects in a cohort of Italian patients treated with cART. A single-center retrospective analysis of patients enrolled from January 2007 to June 2018 was conducted by grouping patients by HBV status and recording baseline viro-immunological features, the history of virological failure, the efficacy of cART in achieving HIV viral undetectability, viral blip detection and viral rebound on follow up. Among 231 enrolled patients, 10 (4.3%) were HBV surface (s) antigen (HBsAg)-positive, 85 (36.8%) were positive for antibodies to HBV c antigen (HBcAb) and with or without antibodies to HBV s antigen (HBsAb), and 136 were (58.9%) HBV-negative. At baseline, HBcAb/HBsAb+/−-positive patients had lower CD4+ cell counts and CD4+ nadirs (188 cell/mmc, IQR 78–334, p = 0.02 and 176 cell/mmc, IQR 52–284, p = 0,001, respectively). There were significantly higher numbers of AIDS and non-AIDS events in the HBcAb+/HBsAb+/−-positive subjects than in the HBV-negative patients (41.1% vs 19.1%, p = 0.002 and 56.5% vs 28.7%, respectively, p ≤ 0.0001); additionally, HIV viremia undetectability was achieved a significantly longer time after cART was begun in the former than in the latter population (6 vs 4 months, p = 0.0001). Cox multivariable analysis confirmed that after starting cART, an HBcAb+/HBsAb+/−-positive status is a risk factor for a lower odds of achieving virological success and a higher risk of experiencing virological rebound (AHR 0.63, CI 95% 0.46–0.87, p = 0.004 and AHR 2.52, CI 95% 1.09–5.80, p = 0.030). HBcAb-positive status resulted in a delay in achieving HIV

The aim of this study was to evaluate the role of baseline lymphocyte subset counts in predicting the outcome and severity of COVID-19 patients. Hospitalized patients confirmed to be infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were included and classified according to in-hospital mortality (survivors/nonsurvivors) and the maximal oxygen support/ventilation supply required (nonsevere/severe). Demographics, clinical and laboratory data, and peripheral blood lymphocyte subsets were retrospectively analyzed. Overall, 160 patients were retrospectively included in the study. T-lymphocyte subset (total CD3+, CD3+ CD4+, CD3+ CD8+, CD3+ CD4+ CD8+ double positive [DP] and CD3+ CD4− CD8− double negative [DN]) absolute counts were decreased in nonsurvivors and in patients with severe disease compared to survivors and nonsevere patients (p

This study describes 6 cases of endodontic overfilling with successful clinical outcomes during long-term (up to 35 years) radiographic follow-up. Successful endodontic treatment depends on proper shaping, disinfection, and obturation of root canals. Filling materials should completely fill the root canal space without exceeding the anatomical apex. Overfilling may occur when the filling material extrudes into the periapical tissues beyond the apex. The present case series describes 6 root canal treatments in which overfilling of root canal sealer and gutta-percha accidentally occurred. Patients' teeth were periodically checked with periapical radiographs in order to evaluate the outcomes during long-term follow-up. All cases showed healing and progressive resorption of the extruded materials in the periapex. The present cases showed that if a 3-dimensional seal was present at the apical level, overfilling did not negatively affect the long-term outcomes of root canal treatment.

Background Frailty assessment has acquired an increasing importance in recent years and it has been demonstrated that this vulnerable profile predisposes elderly patients to a worse outcome after surgery. Therefore, it becomes paramount to perform an accurate stratification of surgical risk in elderly undergoing emergency surgery. Study design 1024 patients older than 65 years who required urgent surgical procedures were prospectively recruited from 38 Italian centers participating to the multicentric FRAILESEL (Frailty and Emergency Surgery in the Elderly) study, between December 2016 and May 2017. A univariate analysis was carried out, with the purpose of developing a frailty index in emergency surgery called “EmSFI”. Receiver operating characteristic curve analysis was then performed to test the accuracy of our predictive score. Results 784 elderly patients were consecutively enrolled, constituting the development set and results were validated considering further 240 consecutive patients undergoing colorectal surgical procedures. A logistic regression analysis was performed identifying different EmSFI risk classes. The model exhibited good accuracy as regard to mortality for both the development set (AUC = 0.731 [95% CI 0.654–0.772]; HL test χ2 = 6.780; p = 0.238) and the validation set (AUC = 0.762 [95% CI 0.682–0.842]; HL test χ2 = 7.238; p = 0.299). As concern morbidity, our model showed a moderate accuracy in the development group, whereas a poor discrimination ability was observed in the validation cohort. Conclusions The validated EmSFI represents a reliable and time-sparing tool, despite its discriminative value decreased regarding complications. Thus, further studies are needed to investigate specifically surgical settings, validating the EmSFI prognostic role in assessing the procedure-related morbidity risk.

In emergency situations, such as building fires, the rescue team must quickly undertake the most appropriate intervention strategy aimed at preventing loss of human life. Emerging hardware and software technologies such as sensors, embedded systems, drones, lidar, Cloud, Artificial Intelligence and Building Information Modeling tools, offer exceptional opportunities in this context. In particular, the attempt to combine and integrate the Internet of Things technologies with Building Information Modeling tools is very interesting in the context of future smart cities. In this paper, a potential integration proposal between Building Information Modeling tools and Internet of Things technologies for fire prevention and emergency management has been presented. The architecture system has been described and a simple functional validation of the proposed system has been carried out. Finally, a discussion about the advantages of this integration for the creation of innovative systems for fire safety in buildings has been tackled.

Among the many plants used in traditional medicine we have the plants of the genus Asphodelus, which are present in the Mediterranean area in North Africa and South East Asia, and have been used by indigenous peoples until recently for various pathologies, including: Psoriasis, alopecia areata, acne, burns, nephrolithiasis, toothache, and local inflammation. The scientific literature over the last five years has investigated the various effects of the metabolites extracted from plants of the genus Asphodelus, paying attention to the diuretic, antihypertensive, antimicrobial, anti-inflammatory, and antioxidant effects, and it also has begun to investigate the antitumor properties on tumor cell lines. Studies have been identified through bibliographic research on electronic databases. A total of 574 records were identified on the PubMed, Scopus, Web of Science, and EBSCO databases. After having proceeded to the screening of the articles with the application of the eligibility criteria (all the articles pertaining to the issue Asphodelus), we arrived at a number of 163 articles, and then after the elimination of overlaps, to 82 articles. There are 11 articles which investigate the possible uses of plants of the genus Asphodelus in oral medicine. In oral medicine, the possible uses investigated by the scientific literature are for the treatment of neoplastic (melanoma and oral cancer), viral (herpetic viruses), and microbial diseases (candida, bacteriosis, leishmaniasis), and in the affection of the skin.

Background Despite an impressive effort in clinical research, no standard therapeutic approach for coronavirus disease 2019 (COVID-19) patients has been established, highlighting the need to identify early biomarkers for predicting disease progression and new therapeutic interventions for patient management. The present study aimed to evaluate the involvement of the human endogenous retrovirus -W envelope (HERV-W ENV) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection considering recent findings that HERVs are activated in response to infectious agents and lead to various immunopathological effects. We analysed HERV-W ENV expression in blood cells of COVID-19 patients in correlation with clinical characteristics and have discussed its potential role in the outcome of the disease. Methods We analysed HERV-W ENV expression in blood samples of COVID-19 patients and healthy donors by flow cytometry and quantitative reverse transcriptase PCR analysis, and evaluated its correlation with clinical signs, inflammatory markers, cytokine expression, and disease progression. Findings HERV-W ENV was highly expressed in the leukocytes of COVID-19 patients but not in those of healthy donors. Its expression correlated with the markers of T-cell differentiation and exhaustion and blood cytokine levels. The percentage of HERV-W ENV-positive lymphocytes correlated with inflammatory markers and pneumonia severity in COVID-19 patients. Notably, HERV-W ENV expression reflects the respiratory outcome of patients during hospitalization. Interpretation Given the known immuno- and neuro-pathogenicity of HERV-W ENV protein, it could promote certain pathogenic features of COVID-19 and therefore serve as a biomarker to predict clinical progression of disease and open to further studies for therapeutic intervention. Funding Information available at the end of the manuscript.

Low CD4+ cell count in patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection during combination antiretroviral therapy (cART) has been described; however, notably few studies have investigated coinfected patients positive for antibodies to the HBV c antigen (HBcAb). An observational retrospective study enrolling 190 patients was conducted by grouping patients with respect to HBV status and recording CD4+ T cell counts and percentages (CD4%), CD8+ T cell counts and percentages (CD8%), and the CD4+ to CD8+ T cell ratio (CD4/CD8) at the time of HIV diagnosis, at the start of treatment and at months 1, 2, 3, 4, 5, 6, 12, and 24 after beginning cART. One hundred and twenty patients (63.2%) were negative for previous HBV infection, while 70 (36.8%) were HBcAb-positive. A significant increase in the CD4/CD8 ratio was recorded in HIV monoinfected subjects compared to HBV coinfected patients from months 4 to 12 from the beginning of cART (p value = 0.02 at month 4, p value = 0.005 at month 5, p value = 0.006 at month 6, and p value = 0.008 at month 12). A significant increase in the absolute count of CD8+ T lymphocytes was described from months 2 to 24 from the start of cART in the subgroup of HBV coinfected patients with an AIDS event at the onset of HIV infection. The presence of HBcAb was observed to be associated with reduced CD4/CD8 ratio growth and a significantly higher proportion of subjects with CD4/CD8

Objectives The purpose of this systematic review of the literature is to investigate which of the epoxy-based cements and those based on Tricalciumsilicate (MTA, Bioceramic) have the best sealing capacity through the analysis of studies that have provided a survey model in vitro of bacteria leakage. Source The articles were identified using electronic databases such as PubMed, Scopus, the search was conducted between 8.12.2020 and 31.12.2020 and a last search was conducted on 2.12.2021. Study selection 678 records were identified and after removing the duplicates we obtain 481 records, with the first phase of screening and selection of records we reached 204 and with the application of the inclusion and exclusion criteria we selected 31 articles, only 9 studies made a direct comparison between the two endodontic cement categories and presented data that could be included in the metaanalysis. Data The meta-analysis of first outcome shows an odds ratio of 2.70 C.I.(Confidence Interval) [1.54, 4.73], the test for overall effect has a p value = 0.0005 with a heterogeneity index of I 2 of 9%; The second outcome meta-analysis shows an Odds Ratio of 1.50 C.I. (Confidence Interval) [0.92, 2.46] with a p value of 0.10 with an I 2 of 79%. Conclusion the sealing ability is higher for epoxy resins than for tricalcium silicate-based cements, for observation periods longer than 90 days. Clinical relevance The knowledge of the cement that determines the best sealing ability and resistance to microbial leakage, can be of help for the dentist who has to face clinical situations such as endodontic retreatments whose failure is determined by the persistence of bacteria in the endodontic canals., sealing ability; microbial leakage; endodontic; epoxy resin; MTA

Droplet digital PCR is an innovative and promising approach for highly sensitive quantification of nucleic acids that is being increasingly used in the field of clinical virology, including the setting of hepatitis B virus (HBV). Here, we comprehensively report a robust and reproducible ddPCR assay for the highly sensitive quantification of serum HBV-DNA. The assay showed a limit of detection of 4 copies/ml ( Overall, the availability of assays for the highly sensitive quantification of serum HBV-DNA can provide an added value in optimizing the diagnosis of occult hepatitis B infection, improving the therapeutic management of chronically HBV infected patients, also in the light of innovative drugs (upcoming in clinical practise) aimed at achieving HBV functional cure.

The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of Human Immunodeficiency Virus (HIV) viremia in patients living with HIV (PLWH) who switch a to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC). A retrospective observational multicenter study was conducted on 166 PLWH switching to the 2DR-3TC-based regimen: 58 HBcAb-positive and 108 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly higher percentage of subjects with very low-level viremia at all time points after switching (6th month: &lt, 31% vs 17.6%, p = 0.047, 12th month 34% vs 27.5%, p = 0.001, 24th month 37% vs 34.2, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively) and a higher percentage of subjects with detectable HIV RNA greater than 20 copies/mL 12 and 24 months after switching (12 months 32% vs 11%, p = 0.001, 24 months 37% vs 13.9%, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively). Logistic regression analysis showed that an increase in age of ten years (OR 2.48 (95% CI 1.58–3.89), p &lt, 0.0001) and the presence of HBcAb positivity (OR 2.7 (5% CI 1.05–6.9), p = 0.038) increased the risk of detectability of HIV RNA by nearly three-fold after switching to 2DR-3TC.

Background: Despite an impressive effort in clinical research, no standard therapeutic approach for coronavirus disease 2019 (COVID-19) patients has been established, highlighting the need to identify early biomarkers for predicting disease progression and new therapeutic intervention for patient management. The present study aimed to evaluate the involvement of the human endogenous retrovirus -W envelope (HERV-W ENV) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection considering recent findings that HERVs are activated in response to infectious agents and lead to various immunopathological effects. We analysed HERV-W ENV expression in blood cells of COVID-19 patients in correlation with clinical characteristics and have discussed its potential role in the outcome of the disease. Methods: We analysed HERV-W ENV expression in blood samples of Covid-19 patients and healthy donors by flow cytometry and quantitative reverse transcriptase PCR analysis, and evaluated its correlation with clinical signs, inflammatory markers, cytokine expression, and disease progression. Findings: HERV-W ENV was highly expressed in the leukocytes of COVID-19 patients but not in those of healthy donors. Its expression correlated with the markers of T-cell differentiation and exhaustion and blood cytokine levels. The percentage of HERV-W ENV-positive lymphocytes correlated with inflammatory markers and pneumonia severity in COVID-19 patients. Notably, HERV-W ENV expression reflects the respiratory outcome of patients during hospitalization. Interpretation: Given the known immuno- and neuro-pathogenicity of HERV-W ENV protein, it could promote certain pathogenic features of COVID-19 and therefore serve as a biomarker to predict clinical progression of disease and as a potential therapeutic target. Funding: Genero Innovation Declaration of Interests: C.M. reports grant from Gilead, outside the submitted work; L.S. reports personal fees and other from Merck, Gilead, and Abbvie, grants from Gilead, outside the submitted work; HP and BC receive compensation for their work by Geneuro-Innovation. The other authors declare no competing interests. Ethics Approval Statement: Ethical approval for the collection and use of human samples was obtained from the ethical board of the Hospital, COronaVIrus Disease: Safety and Efficacy of Experimental Treatment (COVID_SEET prot.7562/2020, 9th April 2020, experimental register 46.20).

Our study aimed to investigate the kinetics of SARS-CoV-2 RNA in bile and in different body fluids of two SARS-CoV-2 positive patients with acute cholecystitis by innovative droplet digital PCR (ddPCR) assays. For each patient, nasopharyngeal- and rectal swabs, bile, urine, and plasma samples were collected at different time points for SARS-CoV-2 RNA quantification by two ddPCR assays. For both patients, ddPCR revealed persistent and prolonged detection of viral RNA in the nasopharyngeal swab despite triple-negative or single-positive results by qRT-PCR. In Patient 1, SARS-CoV-2 RNA dropped more rapidly in bile and rectal-swab and declined slowly in nasopharyngeal swab and plasma, becoming undetectable in all compartments 97 days after symptoms started. Conversely, in patient 2, SARS-CoV-2 RNA was detected, even if at low copies, in all body samples (with the exception of urine) up to 75 days after the onset of symptoms. This study highlights that SARS-CoV-2 RNA can persist for a prolonged time in respiratory samples and in several biological samples despite negativity to qRT-PCR, supporting SARS-CoV-2’s ability to provoke persistent and disseminated infection and therefore to contribute to extra-pulmonary clinical manifestations.

The anti-HBc-positive/HBsAg-negative status is frequent in HIV-infection and correlates with poor survival. Here, by highly-sensitive assays, we evaluate cryptic HBV replication and factors correlated with its detection in 81 anti-HBc-positive/HBsAg-negative HIV-infected patients. Patients were treated for &gt, 12 months with HBV-active modern combined antiretroviral-therapy (cART) and had serum HBV-DNA &lt, 20 IU/mL by commercial Real-Time PCR. Serum HBV-DNA was quantified by droplet digital PCR, serum HBV-RNA by an Abbott research assay, and anti-HBc titer (proposed to infer intrahepatic cccDNA) by Lumipulse/Fujirebio. Cryptic serum HBV-DNA was detected in 29.6% of patients (median (IQR): 4(1&ndash, 15) IU/mL) and serum HBV-RNA in 3.7% of patients despite HBsAg-negativity and HBV-active cART. Notably, cryptic serum HBV-DNA correlated with an advanced CDC-stage (p = 0.01) and a lower anti-HBs titer (p = 0.05), while serum HBV-RNA correlated with lower nadir CD4+ cell-count (p = 0.01). By analyzing serological HBV-markers, the combination of anti-HBs &lt, 50 mIU/mL (indicating lower immune response) plus anti-HBc &gt, 15COI (reflecting higher HBV replicative activity) was predictive of cryptic serum HBV-DNA (OR: 4.7(1.1&ndash, 21.7), p = 0.046, PPV = 62.5%, and NPV = 72%). In conclusion, cryptic HBV-replication (not detected by classical assays) characterizes a conspicuous set of anti-HBc-positive HIV-infected patients despite HBsAg-negativity and HBV-active combined antiretroviral therapy (cART). The integration of classical and novel markers may help identify patients with cryptic HBV-replication, thus optimizing the monitoring of anti-HBc-positive/HBsAg-negative HIV-infected patients.

Propionibacterium are anaerobic/aero-tolerant rod Gram-positive bacteria, and numerous studies are associated with primary and secondary endodontic infections. The data in the literature on the prevalence of Propionibacterium are conflicting, and there are studies that report conflicting data on the prevalence in primary and secondary endodontic infections. This review aims to clarify the prevalence of bacteria of the genus Propionibacterium in endodontic lesions. The present systematic review work was performed on the basis of the Prisma protocol. A search was carried out on the PubMed and Scopus databases with the use of keywords. The research produced 410 records, which, after the elimination of the overlaps and the application of the inclusion and exclusion criteria, led to a number of 36 included articles divided by the three outcomes. The first outcome concerns prevalence of bacteria of the genus Propionibacterium in primary and secondary endodontic lesions. The secondary outcome, differences in the prevalence of bacteria of the genus Propionibacterium between primary endodontic infections and secondary endodontic infections. The tertiary outcome, differences in the prevalence of Propionibacterium Acnes compared to Propionibacterium propionicum in endodontic infections. The results of the meta-analysis show that the genus Propionibacterium bacteria are more prevalent in secondary endodontic infections and that P. Acnes has a higher prevalence than P. propionicum.

INTRODUCTION Infection with hepatitis B virus (HBV) genotype G has been associated with increased liver fibrosis levels compared with other genotypes in cross-sectional studies, yet its role in fibrosis evolution remains to be established. METHODS In this prospective cohort study, 158 human immunodeficiency virus (HIV)-HBV coinfected patients had available HBV genotyping at baseline. Liver fibrosis was assessed at baseline and every 6 to 12 months by the FibroTest (BioPredictive, Paris, France). Risk factors for fibrosis regression (F3-F4 to F0-F1-F2) and progression (F0-F1-F2 to F3-F4) between baseline and end of follow-up were evaluated. RESULTS Most patients were male (88.6%) with a median age of 39 years. HBV genotype A was more prevalent compared with other HBV genotypes (62.7% vs D = 10.8%, E = 10.8%, and G = 15.8%). Patients were followed up for a median of 83 months (IQR = 37-97). In the 43 (27.2%) patients with F3-F4 baseline liver fibrosis, 7 (16.2%) regressed to F0-F1-F2 fibrosis at the last follow-up visit. In the 115 (72.8%) with F0-F1-F2 fibrosis at baseline, 19 (16.5%) progressed to F3-F4 fibrosis at last visit. In multivariable analysis, fibrosis progression was independently associated with older age (P

Objective:The purpose of this study was to evaluate dentinal microcrack formation during root canal treatment using Mtwo NiTi rotary instruments and MicroSeal filling technique.Materials and Methods:Forty-five single-rooted teeth were selected for the present study and divided into 3 different groups ( n = 15): Group 1, in which root canals were instrumented with Mtwo rotary files; Group 2, in which root canals were instrumented with Mtwo rotary files and filled using the MicroSeal technique; and Group 3, that acts as a control group in which no instrumentation nor obturation were performed. Then, roots were sectioned 3 mm, 6 mm, and 9 mm from the apex and the cut surface has been observed under a stereomicroscope to check for the presence or absence of dentinal microcracks. Number of dentinal microcracks was registered for each group at different levels and data were statistically analyzed using the Chi-square test with a level of significance set at P < .05.Results:No statistically significant differences were registered among groups ( P < .05). No microcracks were detected in Groups 1 and 3, while two dentinal microcracks were registered in Group 2.Conclusions:Mtwo rotary instruments and the MicroSeal root canal filling technique did not significantly induce dentinal microcrack formation.

ObjectivesTo evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy.MethodsDynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999–2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm).ResultsAmong 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P ConclusionsA dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.

In recent years, a decrease in the incidence of tuberculosis (TB) has been recorded worldwide. However, an increase in TB cases has been reported in foreign people living in low-incidence countries, with an increase in extrapulmonary TB (EPTB) in the western region of the world. In the present work, a retrospective study was conducted in two Italian infectious diseases wards to evaluate the clinical characteristics of TB admission in the time period 2013&ndash, 2017. A significant increase in TB was shown in the study period: 166 (71% males) patients with TB were enrolled, with ~70% coming from outside Italy (30% from Africa, 25% from Europe, and 13% from Asia and South America). Compared to foreign people, Italians were significantly older (71.5 (interquartile range, IQR: 44.5&ndash, 80.0) vs. 30 (IQR: 24&ndash, 40) years, p &lt, 0.0001) more immunocompromised (48% vs. 17%, 0.0001), and affected by comorbidities (44% vs. 14%, 0.0001). EPTB represented 37% of all forms of the disease, and it was more incident in subjects coming from Africa than in those coming from Europe (39.3% vs. 20%, respectively). In logistic regression analysis, being European was protective (odd ratio, OR (95% CI): 0.2 (0.1&ndash, 0.6), p = 0.004) against the development of EPTB forms. In conclusion, an increase in the rate of TB diagnosis was documented in two Italian reference centers in the period 2013&ndash, 2017, with 39% of EPTB diagnosed in patients from outside Europe.

Worldwide, approximately 10% of all human immunodeficiency virus (HIV)-infected people are also chronically coinfected with hepatitis B virus (HBV). HBV infection has a poor prognosis in HIV-positive people and has been documented by an increased risk of developing chronic HBV infection (CHB), progression to liver fibrosis and end-stage liver disease (ESLD) and evolution of hepatocellular carcinoma (HCC). Furthermore, in HIV patients, HBV-resolved infection is often associated with the appearance of HBV-DNA, which configures occult HBV infection (OBI) as a condition to be explored in coinfected patients. In this narrative review we summarize the main aspects of HBV infection in HIV-positive patients, emphasizing the importance of carefully considering the coinfected patient in the context of therapeutic strategies of antiretroviral therapy.

Background Although several cases of hepatitis B virus reactivation have been described in patients with a history of hepatitis B virus infection while undergoing treatment for hepatitis C virus infection with direct acting antivirals, the question of whether hepatitis B virus surface antigen immune-escape mutations might play a role has not been addressed so far. Case presentation We report a case of hepatitis B virus reactivation in a Caucasian patient infected with hepatitis C virus during treatment with sofosbuvir and velpatasvir. A 50-year-old man with a genotype 1a hepatitis C virus infection was considered for therapy. His serological profile was hepatitis B virus surface antigen-negative, hepatitis B virus core antibody-positive, hepatitis B virus surface antibody-negative, and anti-hepatitis D virus-positive. The detection of hepatitis B virus deoxyribonucleic acid (DNA) indicated active viral replication during the direct acting antiviral treatment that spontaneously returned to undetectable levels after treatment completion. Starting from week 12 after the end of treatment, hepatitis B virus surface antibody titers and hepatitis B virus e antibody developed. Sequencing analysis revealed the hepatitis B virus genotype D3 and the presence of two relevant immune-escape mutations (P120S and T126I) in the major hydrophilic region by analyzing the S region. Conclusions We speculate that the presence of the hepatitis B virus surface antigen mutations, endowed with the enhanced capability to elude the immune response, could play a role in hepatitis B virus reactivation. This observation confirms that occult hepatitis B infection should also be carefully monitored, through surveillance of the hepatitis B virus viral load before and during direct acting antiviral treatment of hepatitis C virus.

Hepatitis B virus (HBV) persistence is at the basis of HBV reactivation as a consequence of chemotherapy and immunosuppressive treatments. The identification of early viral replication indicators and markers of effective HBV immunological control would be useful in monitoring patients who are at risk of potential viral reactivation during the course of immunosuppressive treatment. Currently, international guidelines have shared some criteria to identify patients with a low, medium or high risk of HBV reactivation; however, permanently placing a patient in a definitive category is not always easy. More often, patients move from one category to another during the course of their immunosuppressive treatment; therefore, in many cases, there are no precise indicators or tools for monitoring possible reactivation and establishing the duration and suspension of antiviral prophylaxis. Historically, the sequence of HBV antigens and antibodies and HBV DNA levels has been used to evaluate the different stages of the acute and chronic phases of an HBV infection. In the last few years, new biomarkers, such as anti-HBs and anti-HBc titres, HBV core-related antigen (HBcrAg), ultra-sensitive HBsAg evaluation and HBV RNA, have been used in patients with an HBV infection to evaluate their diagnostic and prognostic potential. The aim of this review is to evaluate the published results on the use of new infection markers in the diagnosis and monitoring of HBV reactivation over the course of immunosuppressive treatments. Moreover, the importance of viral genotypic studies was emphasized, given the diagnostic and therapeutic implications of the mutational profiles of HBsAg during the HBV reactivation phase.

Electric production from renewable resources, such as solar photovoltaic (PV), is playing an increasingly essential role in the agricultural industry because of the progressive increase in the energy price from fossil fuels and the simultaneous decrease in the income deriving from farming activities. A central issue in the sustainable diffusion of PV technologies is represented by the actual energy efficiency of a PV system. For these reasons, a performance analysis has been carried out in order to assess the potentials offered by different PV plants within a defined geographical context with the aim of investigating the impact of each component has on the PV generator global efficiency and defining the main technical parameters that allow to maximise the annual specific electric energy yield of an architectonically integrated plant, installed in a dairy house, compared to a ground-mounted plant. The annual performances of three grid connected PV plants installed in the same dairy cattle farm have been analysed: two are architectonically integrated plants - i.e., a rooftop unidirectional and a multi-field systems (both 99 kWp) - and the other is a ground-mounted plant (480 kWp). Furthermore, the electrical performances, estimated by the photovoltaic geographical information system (PVGIS), developed by the EU Joint Research Centre, and by an analytical estimation procedure (AEP), developed on the basis of a meteo-climatic database related to the records of the nearest weather station and integrated by the components’ technical specifications, have been compared with the actual yields. The best annual performance has been given by the ground-mounted PV system, with an actual increase of 26% and in the range of 6÷12% according to different estimations, compared to the integrated systems, which were globally less efficient (average total loss of 26÷27% compared to 24% of the ground-mounted system). The AEP and PVGIS software estimates showed a good level of reliability for mean deviations between the annual actual and estimated electrical power yields have been equal to 11.5% for each PV system given the actual irradiation’ s uncertainty during the examined year. The main technical parameters, crucial to maximise the energy yield from a ground-mounted PV system to an integrated one, have been identified in the Tilt and Azimuth angles. Indeed, once a variance of 3÷4% in the global efficiency has been confirmed when the type of PV system is changed, in the case of the unidirectional integrated PV plant, the high roof pitch and the almost South orientation guarantee a solar energy increase up to 18% higher than that obtainable on the horizontal plane and similar to the increase estimated for the ground-mounted generator (+20%). Hence, integrated PV systems, besides reaching the same levels of energy efficiency as those ground-mounted, are also more sustainable than the latter. This is true providing that there are both a suitable orientation and an accurate design, especially to prevent the PV panels’ warming during summer, on an already available surface that is, however, functional to the roof’s architecture.

Cultural heritage is a complex ecosystem requiring innovative methods and techniques to facilitate its restoration, management and valorization. In detail, restoration processes have to preserve the original characteristics of historical buildings or sites, by involving different professional figures, each one with different roles, responsibilities and skills. In this light, a system that facilitates the information management, supported by new technologies, could allow more precise, efficient and traceable information exchange and could optimize the construction and management operative phase. Starting from these assumptions, the research proposes the application of a new integrated approach to a restoration process of a historical building. It consists of applying Business Process Management (BPM) approach and Building Information Modeling (BIM) methodology to provide valuable insights to optimize the data flow, to gather information and to share knowledge during the restoration process, by optimizing the whole lifecycle management process, by facilitating the ordinary and extraordinary maintenance. All these aspects are essential and strategic for the Italian cultural heritage.

The development of biogas production exacerbated the competition for land availability between crops dedicated to human consumption and those intended for energy production. Residual biomasses have been often proposed for their positive outcomes in terms of reduced pressure on land use. However, literature did not assess optimization options for existing biogas plants feeding. This paper developed a bio-economic model for the optimization of agricultural biogas supply chains using artichoke byproducts in existing plants. A multiple goal linear programming approach was adopted, using two objective functions, calculating respectively net present value and land use from energy crops, associated to a regional biogas network. Three scenarios were defined using primary and secondary data on the residues of a specific artichoke variety - globe - and an Italian region - Sardinia. In the Business As Usual scenario, net present value is about 7 million € with a land use of about 2720 ha. When using artichoke residues, the economic impact increases by 28% and land use is reduced by 83% if net present value is optimized. When land use is optimized, the economic impact still grows by 25% and land use is reduced by 100%. Results from this study confirm that, under certain conditions, locally available residual biomasses can replace energy crops in existing biogas networks, coupling viability and sustainability.

Highlights • Ocrelizumab is not associated to increased severity in MS patients with COVID-19. • B-cell depleting treatment could impact on virus-specific antibody production. • B-cell depleting therapies can reduce IL-6 production, thus modulating inflammation., Background Recently SARS-CoV-2 has spread worldwide causing a pandemic. Little is known about disease severity in immunocompromised hosts and people receiving disease modifying therapies (DMTs). In the last decades DMTs have been widely employed, and ocrelizumab represents one of the newest therapies for the relapsing remitting and progressive forms of multiple sclerosis (MS). Objectives to describe SARS-CoV-2 related pneumonia in two MS patients under ocrelizumab treatment. Methods Case series. Results Patients showed a mild clinical course of SARS-CoV-2 related pneumonia without complications or sequelae. Conclusion Ocrelizumab treatment is not necessarily associated to increased severity in MS patients with SARS-CoV-2 infection.

OBJECTIVES: The aim of the study was to compare the intra-individual plasma and intracellular peripheral blood mononuclear cell (PBMC) pharmacokinetics (PK) of tenofovir (TFV) and its intracellular metabolite, tenofovir-diphosphate (TFV-DP) in patients switched from a fixed dose combination (FDC) tablet of tenofovir disoproxil fumarate (TDF)/ emtricitabine (FTC)/ elvitegravir (EVG)/ cobicistat (COBI) to a FDC containing tenofovir alafenamide (TAF)/FTC/EVG/COBI. DESIGN: A single arm, prospective, non-randomized, cross-over, PK study in patients receiving a TDF-containing regimen (TDF 300mg/ FTC 200mg/ EVG 150mg/ COBI 150mg) switched to a TAF-containing FDC regimen (TAF 10mg/ FTC 200mg/ EVG 150mg/ COBI 150mg). METHODS: Single, sparse plasma and PBMC samples were collected during TDF therapy and 4 to 8 weeks post-switch to the TAF-containing regimen. Plasma TFV and cell associated TFV-DP concentrations were determined with validated liquid chromatography tandem mass spectrometry methods. PBMC cell enumeration was performed by quantification of RNaseP (RPP30) gene copy numbers using a highly sensitive droplet digital PCR (ddPCR) assay. Plasma and PBMC PK were summarized as geometric mean (GSD) and compared as a geometric mean ratio with a Wilcoxon Signed Rank test. RESULTS: In 30 participants with evaluable data, TFV plasma concentrations decreased 90% [TDF: 99.98 (2.24) ng/mL vs TAF: 10.2 (1.6) ng/mL, p

Background Occult hepatitis B infection (OBI) is recognized as a risk factor for cirrhosis and hepato-cellular carcinoma. However, OBI brings together a large spectrum of patients who might harbor different characteristics and prognosis. Methods We analyzed the databases of a university hospital in Paris to identify OBI among patients (n = 3966) concomitantly tested for hepatitis B virus (HBV) DNA and serology during a 7-year period. OBI patients were gathered into clinical entities according to their clinical records. Results Forty-seven OBIs were identified (1.2%). All patients had detectable anti-HBc, isolated (n = 26) or associated with anti-HBs (n = 21). The proportion of OBIs was 3.4% for patients with isolated anti-HBc and 4.2% for patients with both anti-HBc and anti-HBs. Four clinical categories of OBI patients were identified: patients with a passed HBV infection with HBs Ag clearance (group A, 23.4%); HBV-exposed patients receiving immunosuppressive therapy (group B, 29.8%); HIV/HBV-coinfected patients with therapy discontinuation (group C, 17%); HBV-exposed patients with severe liver conditions (group D, 29.8%). Significant follow-up was available for 32 patients, showing a more deleterious prognosis in group D patients, associated more with their underlying condition than the OBI status. Conclusions OBI is a heterogeneous condition with various clinical implications.

Hepatitis B virus (HBV) genotype E almost exclusively occurs in African people, and its presence is more commonly associated with the development of chronic HBV (CHB) infection. Moreover, an epidemiological link has been found between the distribution of HBV genotype E infection and African countries with high incidences of hepatocellular carcinoma. As part of a programme for the health assessment of migrants, we evaluated 358 young African subjects for HBV infection; 58.1% (208/358) were positive for an HBV marker, and 54 (25.5%) had CHB. Eighty-one percent of the CHB subjects were infected with HBV genotype E, with a median serum HBV-DNA of 3.2 (IQR: 2.7-3.6) logIU/ml. All patients had high serum HBsAg titres (10,899 [range 5,359-20,272] IU/ml), and no correlation was found between HBsAg titres and HBV-DNA plasma levels. RT sequence analysis showed the presence of a number of immune escape mutations: strains from all of the patients had a serine at HBsAg position 140; 3 also had T116N, Y100C, and P142L+S143L substitutions; and 1 had a G112R substitution. Six (18%) patients had stop-codons at position 216. In 5 of the 9 (26.5%) CHB patients, ultrasound liver biopsy, quantification of total intrahepatic HBV-DNA and cccDNA, and RT/HBsAg sequencing were performed. The median (IQR) total intrahepatic HBV-DNA was 766 (753-1139) copies/1000 cells, and the median (IQR) cccDNA was 17 (10-27) copies/1000 cells. Correlations were observed for both total intrahepatic HBV-DNA and cccDNA with serum HBV-DNA, while no correlation was found for the HBsAg titres. A difference of 2.5/1,000 nucleotides was found in the HBsAg sequences obtained from plasma and from liver tissue, with 3 cases of possible viral anatomical compartmentalization. In conclusion, a high rate of CHB infection due to the E genotype was demonstrated in a group of immigrants from Western Africa. An analysis of the viral strains obtained showed the virological characteristics of immune escape, which may be the cause of viral replication persistence. Moreover, a fair percentage of stop codon mutations were found. The lack of correlation between HBsAg titres and plasma or intrahepatic HBV-DNA found in these subjects suggests a pathway of virus production that is not linked to HBsAg secretion. Studies with a larger number of patients with CHB due to the E genotype are advisable to corroborate these observations.

Objectives Increasing line of evidence indicates that the NKG2D-activating receptor plays a relevant role in the effector functions of cytotoxic lymphocytes. In this study, we investigated the expression and function of NKG2D in CD8⁺ T cells from chronically HIV-1-infected patients with or without antiretroviral therapy (ART). Methods We measured by flow cytometry the expression of NKG2D on CD8⁺ T-cell subsets of ART-naive and ART patients as well as seronegative healthy subjects (HIV-neg). An intrapatient analysis before and after ART initiation was also performed. Results were correlated with viral load, CD4⁺ T-cell counts, markers of immune activation (CD38, sCD14), and soluble NKG2D ligands (sMICA and sULBP2). The function of NKG2D on CD8⁺ T cell cytotoxicity was tested by ex vivo degranulation assays. Results We showed that NKG2D was downregulated on all CD8⁺ T-cell subsets of ART-naive patients. The expression of NKG2D on CD8⁺ T cells inversely correlated with viral load and CD38 expression but not with plasma levels of sMICA and sULBP2. Importantly, we found that NKG2D-mediated costimulation of CD8⁺ T-cell lytic activity was strongly reduced in ART-naive patients if compared with HIV-neg and ART subjects. Finally, intrapatient analysis demonstrated that effective anti-HIV-1 therapy restores NKG2D expression and NKG2D-induced cytotoxicity by CD8⁺ T cells. Conclusions These data underscore that NKG2D downregulation contributes to impaired CD8⁺ T-cell responses in untreated HIV-1 infection and have implications for monitoring immune functions and response to treatments, and for the development of novel anti-HIV-1 strategies combining ART with drugs that stimulate NKG2D expression and function.

Aim Aim of this study is to analyze the real movement, influenced by anatomical difficulties, of nickel-titanium rotary instruments within root canal systems; then the objective is to point out the physical and geometrical characteristics of an ideal instrument, able to overcome the most complex anatomies. Methodology At first, observation of the behavior of nickel-titanium rotary instruments within root canal systems and of the influence on them of root canal anatomy. Then, attempt to avoid the anatomical obstructions exploiting, with manual rotation, the advantages of a zero/low torque. Results Given that, in some root canals the severity of the curves prevents instruments to advance in rotation, we obtained significant results by manually advancing and rotating NiTi rotary instruments. Conclusions Therefore, in some cases, we would need an instrument that can reconcile efficiency with a reduction of mass and torque; the ideal instrument should have a very contained working part, combining efficiency with the decrease of mass and, consequently, of torsional stresses too.

Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N= 200) and whenever possible at baseline (N= 70). Results: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P= 2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure. Conclusions: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring.