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Purpose: To investigate and analyze the effects of different prosthetic protocols under different loading and occlusal conditions on the survival rates of single implants immediately placed into fresh extraction sockets of maxillary or mandibular premolars with single-stage surgery. Materials and Methods: Patients needing replacement of a single premolar in the maxilla or mandible were included and randomly divided into three groups based on the different loading protocols: group 1 = healing abutment; group 2 = provisional crown left out of occlusion without functional loading; and group 3 = provisional crown in functional occlusion in maximum intercuspation without contact in excursions. The hypothesis was that single implants inserted into fresh extraction sockets and immediately connected to a temporary crown under functional loading would demonstrate survival rates comparable to single implants placed in the same conditions connected to a healing abutment or to an immediate temporary crown left out of occlusion. Results: A total of 112 patients were treated, and 126 implants were placed (92 in the maxilla and 34 in the mandible). After a mean follow-up of 2.5 years (range 1 to 5 years), there were no failures in groups 1 or 2. Two implants failed in group 3 (one in the maxilla, one in the mandible). The cumulative survival rate was 98.5% across all groups, with 100% in groups 1 and 2 and 95% in group 3. Statistical analysis showed that group 3 displayed a survival rate comparable to groups 1 and 2 (P = .08). Conclusion: Within the limitations of this study, no significant differences were found in terms of implant survival rates between implants inserted into fresh extraction sockets without loading vs with immediate nonfunctional or functional loading. [ABSTRACT FROM AUTHOR]

Despite the common belief that the granting of a patent is a neutral act, patent protection is intended to encourage technological innovations that are acceptable from an ethical point of view: in fact, both international and supranational legislation exclude from patentability inventions whose commercial exploitation would be contrary to ordre public, a notion that certainly encompasses also the prevention of serious damage to the environment. However, the provisions excluding the patentability of inventions whose commercial exploitation is contrary to ordre public (and in particular to environmental ordre public) have rarely been applied in Europe. After outlining the reasons why ordre public exceptions have had very limited application in Europe so far, the paper offers a new perspective through which such exceptions should be interpreted and suggests how patent offices can play a new and more decisive role in promoting environmentally sustainable innovation. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the role of different healing abutment designs in compensating for the buccolingual volumetric tissue change that occurs following flapless single-tooth immediate extraction placement in the molar area. Materials and Methods: Patients in need of extraction and replacement of a first or second molar in the mandible or maxilla were consecutively recruited. Immediately after extraction and implant placement, an abutment was connected. Five different types of abutments were randomly selected to be used for each case. The study population was divided into five categories according to abutment design: 5-mm diameter healing abutment (group 1); 6-mm diameter healing abutment (group 2); 7.5-mm diameter healing abutment (group 3); provisional restoration (group 4); and customized healing abutment (group 5). The buccopalatal dimension (BPD) was measured on the study casts at 1, 3, and 5 mm apical to the free gingival margin, and horizontal volumetric changes were compared between baseline and 2, 4, and 6 months. Results: A total of 267 implants were inserted in 246 patients. The breakdown of placed implants for each group was as follows: 67 implants in group 1; 64 in group 2; 71 in group 3; 33 in group 4; and 32 in group 5. Changes in the mean horizontal ridge dimension were as follows. After 6 months in group 1, BPD diminished at 1-, 3-, and 5-mm distance from the free gingival margin, respectively, by 4.21 ± 0.158, 3.38 ± 0. 178 and 2.35 ± 0.178 mm. In group 2, BPD diminished at 1-, 3-, and 5-mm distance from the free gingival margin, respectively, by 3.16 ± 0.198, 2.56 ± 0.198, and 1.62 ± 0.198 mm. In group 3, BPD diminished at 1-, 3-, and 5-mm distance from the free gingival margin, respectively, by 2.53 ± 0.138, 2.16 ± 0.144, and 1.56 ± 0.144 mm. In group 4, BPD diminished at 1-, 3-, and 5-mm distance from the free gingival margin, respectively, by 1.11 ± 0.179, 1.23 ± 0.179, and 1.12 ± 0.179 mm. In group 5, BPD diminished at 1-, 3-, and 5-mm distance from the free gingival margin, respectively, by 0.25 ± 0.225, 0.30 ± 0.225, and 0.19 ± 0.225 mm. Mixed-effect regression and post hoc means comparisons were used to model the impact of the restoration technique, height of measurement, and time on BPD using a significance reference level of .05. Statistical analysis showed that the type of abutment, the height of measurement, and the time significantly influenced the BPD and that there were complex interaction effects between these variables. Conclusion: The observed volumetric soft tissue changes in the 6-month short-term follow-up appeared to vary based on the use of different healing abutment sizes that were connected to implants placed immediately after tooth extraction in the molar area. In particular, the use of a customized healing abutment resulted in preservation of the original horizontal dimension of the molar soft tissue. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the survival and success rate of and the incidence of complications affecting implants inserted and immediately loaded in sites where an impacted tooth was present in the maxilla. Materials and methods: A total of 10 patients were treated and 14 implants were inserted, 4 in healed sites and 10 in extraction sites. The implant site preparation started in the crestal bone and continued in the enamel and dentine of the impacted tooth. The radiographic depth of implant penetration into the impacted tooth, peri-implant soft tissue and hard tissue condition at the 1-year follow-up and the last follow-up appointment, marginal bone loss at the 1-year follow-up and the last follow-up appointment, and the final aesthetic result were evaluated. Results: The implants healed uneventfully with an adequate hard and soft tissue response and no adverse clinical or radiographic signs or symptoms. They were in function for a minimum of 3 and a maximum of 11 years (mean 7.2 years). Conclusion: Although further studies with a larger sample size are required to validate this unconventional approach, it can be considered a valuable clinical option to replace teeth in an area of impaction. [ABSTRACT FROM AUTHOR]

This article aims to evaluate the effect of anatomically designed, single-unit provisional restorations on soft tissue preservation following immediate implant placement. Patients in need of a single-tooth replacement in the esthetic area were recruited for this study. An immediate provisional restoration with a transmucosal area anatomically designed to support the soft tissue was used for every patient. The horizontal volumetric tissue changes and the presence and amount of vertical recession were measured at baseline (T0) and after 1 month (T1), 3 months (T2), and 6 months (T3). Sixty-three patients received 66 implants that were placed into fresh extraction sites. The average follow-up time was 48 months (range: 24 to 60 months). All implant restorations were successful, and the cumulative implant survival rate and success of restorations was 100%. After 6 months, the mean horizontal ridge measured midbuccally had increased by 0.10 ± 0.10 mm at 1 mm from the free gingival margin, had decreased by 0.09 ± 0.10 mm at 3 mm, and had decreased by 0.20 ± 0.10 mm at 5 mm. In addition, the mean recession at the midbuccal surfaces was 0.04 ± 0.37 mm. Measurements were made clinically and compared to measurements made on the casts. According to the results of this study, the use of customized anatomically designed immediate provisional restorations following single-tooth extraction and immediate implant placement appeared to minimize the loss of tissue volume that results from postextraction bone remodeling, thus optimizing the final esthetic result. [ABSTRACT FROM AUTHOR]

The goal of this study was to evaluate the cumulative survival rate and marginal bone loss (MBL) of extra-short (5- and 6-mm-long) and short (6.5-mm-long) implants inserted into severely atrophic, partially edentulous posterior maxillae and mandibles that were immediately restored with provisional fixed dental prostheses. Materials and Methods: Between October 2013 and December 2017, partially edentulous patients with severe vertical bone atrophy in the posterior area in need of replacement of premolars and/or molars with fixed prostheses were enrolled in the study. Analysis of cumulative survival rate and MBL was determined with respect to implant length at the longest, biannual follow-up period (38 ± 10 months; range: 25 to 48 months). Results: Fifty-five patients were included in the study. A total of 62 extra-short (5 and 6 mm), 15 short (6.5 mm), and 69 standard-length (≥ 10 mm) implants were immediately placed and loaded. Cumulative survival rates were similar for all implants (99.3%). One mandibular extra-short implant failed and was removed but was replaced 2 months later with another implant of the same length and diameter and successfully reloaded. Implant length did not impart any significant differences in MBL, though the presence or absence of platform switching was influential. Conclusion: The cumulative survival rate and MBL reported in this study encourage the use of short and extra-short implants to immediately restore with fixed prostheses partially edentulous patients with severe vertical bone atrophy in posterior areas. Thus, it could be an alternative treatment to vertical bone augmentation. [ABSTRACT FROM AUTHOR]

Background. Alpha-1 antitrypsin deficiency (AATD) can result in severe liver and respiratory disorders. The uninhibited elastase activity on the elastic tissue of arterial walls suggests that AATD may also impact vascular health. Thus, we performed a meta-analysis of the studies evaluating cardiovascular risk in individuals with AATD and non-AATD controls. Methods. A systematic literature search was conducted in the main scientific databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Differences between cases and controls were expressed as odds ratios (OR) with 95% confidence intervals (95%CI). The protocol was registered on PROSPERO under the identification number CRD42023429756. Results. The analysis of eight studies showed that, with a prevented fraction of disease of 15.0% and a corresponding OR of 0.779 (95%CI: 0.665–0.912; p = 0.002), a total of 24,428 individuals with AATD exhibited a significantly lower risk of ischemic heart disease compared to 534,654 non-AATD controls. Accordingly, given a prevented fraction of disease of 19.5%, a lower risk of acute myocardial infarction was documented when analyzing four studies on 21,741 cases and 513,733 controls (OR: 0.774; 95%CI: 0.599–0.999; p = 0.049). Sensitivity and subgroup analyses substantially confirmed results. Meta-regression models suggested that these findings were not influenced by AATD genotypes or prevalence of chronic obstructive pulmonary disease (COPD) among cases and controls, while higher differences in the prevalence of male sex (Z-score: 3.40; p < 0.001), hypertension (Z-score: 2.31; p = 0.021), and diabetes (Z-score: 4.25; p < 0.001) were associated with a lower effect size. Conclusions. Individuals with AATD may exhibit a reduced risk of ischemic heart disease, even in the presence of mild deficiency of the serine protease inhibitor. Although caution is warranted due to the observational nature of the data, future pharmacological and rehabilitation strategies should also take this controversial relationship into account. [ABSTRACT FROM AUTHOR]

Background and Objectives: The treatment of end-stage ankle osteoarthritis (OA) and associated hindfoot deformities remains a major challenge for orthopedic surgeons. Numerous techniques and surgical approaches have been proposed for tibiotalar (TT) and tibiotalocalcaneal (TTC) arthrodesis, from arthroscopic to open, as well as numerous devices proposed for internal fixation (retrograde intramedullary nails, cannulated screws, and plating systems). The aim of this study was to retrospectively analyze the results, with at least 18 months of follow-up, with SilverbackTM TT/TTC Plating System Paragon28 in a group of 20 patients with severe OA and hindfoot deformities (mainly secondary post-traumatic OA). Materials and Methods: The demographic characteristics and past medical history of the patients were collected and analyzed to identify the cause of the pathology. The degree of OA and deformity were quantified based on foot and ankle weight-bearing radiography and CT examination. Pre- and post-operative clinical and functional scores (ROM, VAS, AOFAS, FFI, and SF-36) and radiographic parameters (anterior distal tibial angle, tibiotalar angle, coronal tibiotalar angle, and hindfoot alignment angle) were evaluated. Results: All of the patients showed clinical and radiographic fusion at an average of 14 weeks (range 12–48), with improvement in pain and functional scores, without major surgical complications and/or infections. Conclusions: Despite the limitations of our study, the results with this new plating system showed good results in terms of bone consolidation, post-operative complications, and improvement of pain and quality of life in patients with severe OA and deformities of the ankle and hindfoot. [ABSTRACT FROM AUTHOR]

To provide clinical information on overcorrection to be included in the initial digital setup to make clear aligner therapy (CAT) more efficient. Prescription data for 150 patients (80 women and 70 men; mean age 33.7 ± 12.7 years) treated successfully with CAT (F22 Aligners, Sweden & Martina, Due Carrare, Italy) and requiring only a single, minimal finishing phase were acquired retrospectively. The inclusion criteria were Class I dental malocclusion with only minimal crowding (≤3 mm), 12–20 aligner steps per arch, no use of auxiliaries or interarch elastics, and rotations ≤25° for round-shaped teeth. The prescribed and corrective movements to be achieved in the main and finishing treatment phases, respectively, were quantified by the dedicated clear aligner setup software. The magnitudes of inclination (buccal-lingual crown tipping), angulation (mesial-distal crown tipping), rotation, intrusion, and extrusion were extracted and analyzed by tooth type, maxilla and mandible, and both arches. Descriptive statistics, that is, mean, standard deviation, and percentage, were calculated for each movement investigated. Classification and regression trees (CART) were generated using the model-based recursive partitioning approach, and the corrective movements were correlated with respect to both the amount of the movements prescribed and the tooth type. Statistical significance was set at 5%. Inclination and rotation required the greatest correction, whereas angulation, intrusion, and extrusion required only minimal correction. Expressed as a percentage of prescribed movement, mean corrective movements were 20.5% for inclination, 14.5% angulation, 28.4% rotation, 11.7% extrusion, and 22% intrusion. According to CART, all corrective movements except extrusion depended on both tooth type and the magnitude of prescribed movement. To achieve more efficient CAT, approximately 20% overcorrection should be added to the initial planning phase when planning challenging movements such as inclination and rotation. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the buccopalatal volumetric tissue change that occurs following flapless single-tooth immediate extraction placement in the esthetic area and to analyze the role of four different variables. Materials and Methods: Patients in need of a single-tooth replacement in the anterior maxillary or mandibular area (premolar to premolar) were recruited for the study. Patients were treated using four different therapeutic modalities: group 1 (healing abutment), group 2 (healing abutment + bone graft), group 3 (provisional restoration) and group 4 (provisional + bone graft). Alginate impressions were taken the day of implant insertion before tooth extraction (T0), at 1 month (T1), at 3 months (T2), and at 6 months (T3). Buccopalatal dimension (BPD) was measured on the study casts at 1, 3, and 5 mm apical to the free gingival margin and compared between T0 and T1 and T2 and T3. Results: Seventy-seven patients were included in the study, 29 men and 48 women with a mean age of 54 years (range: 24 to 76 years) and 80 implants were inserted. Thirteen implants were inserted in group 1, 13 in group 2, 20 in group 3, and 34 in group 4. The BPD contraction was more evident for group 1, smaller in group 2 and group 3, and minimal in group 4. Repeated measures analysis of variance (ANOVA) and post hoc tests were used. The data analyzed were considered statistically significant with a level of α = .05. The interaction effect P value was numerically zero. Conclusion: The results of this study seem to indicate that volumetric tissue changes after immediate extraction placement in the esthetic area can be minimized if a provisional is immediately connected and a bone graft is inserted simultaneously [ABSTRACT FROM AUTHOR]

Endothelial dysfunction has been proposed to play a key role in the pathogenesis of coronavirus disease 2019 (COVID-19) and its post-acute sequelae. Flow-mediated dilation (FMD) is recognized as an accurate clinical method to assess endothelial function. Thus, we performed a meta-analysis of the studies evaluating FMD in convalescent COVID-19 patients and controls with no history of COVID-19. A systematic literature search was conducted in the main scientific databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using the random effects method, differences between cases and controls were expressed as mean difference (MD) with 95% confidence intervals (95% CI). The protocol was registered on PROSPERO with reference number CRD42021289684. Twelve studies were included in the final analysis. A total of 644 convalescent COVID-19 patients showed significantly lower FMD values as compared to 662 controls (MD: −2.31%; 95% CI: −3.19, −1.44; p < 0.0001). Similar results were obtained in the sensitivity analysis of the studies that involved participants in either group with no cardiovascular risk factors or history of coronary artery disease (MD: −1.73%; 95% CI: −3.04, −0.41; p = 0.010). Interestingly, when considering studies separately based on enrolment within or after 3 months of symptom onset, results were further confirmed in both short- (MD: −2.20%; 95% CI: −3.35, −1.05; p < 0.0001) and long-term follow-up (MD: −2.53%; 95% CI: −4.19, −0.86; p = 0.003). Meta-regression models showed that an increasing prevalence of post-acute sequelae of COVID-19 was linked to a higher difference in FMD between cases and controls (Z-score: −2.09; p = 0.037). Impaired endothelial function can be documented in convalescent COVID-19 patients, especially when residual clinical manifestations persist. Targeting endothelial dysfunction through pharmacological and rehabilitation strategies may represent an attractive therapeutic option. The mechanisms underlying the post-acute sequelae of coronavirus disease 2019 (COVID-19) have not been fully elucidated. Impaired endothelial function can be documented in convalescent COVID-19 patients for up to 1 year after infection, especially when residual clinical manifestations persist. Targeting endothelial dysfunction may represent an attractive therapeutic option in the post-acute phase of COVID-19. [ABSTRACT FROM AUTHOR]

Background: The use of fractional exhaled nitric oxide (FeNO) has been proposed for identifying and monitoring eosinophilic airway inflammation in chronic obstructive pulmonary disease (COPD). To explore the clinical utility of FeNO in COPD, we aimed to assess its short-term variability in a clinically stable COPD cohort. Methods: Consecutive COPD patients, formerly smokers, underwent FeNO assessment at the baseline and six time-points through serial sampling spaced 3 days apart. Results: A total of 41 patients (mean age 72.9, 87.8% males) showed a median baseline value of FeNO of 11.7 (8.0–16.8) ppb. A weak linear relationship was documented between baseline FeNO values and both eosinophil counts (r = 0.341, p = 0.029) and the percentage of eosinophils (r = 0.331, p = 0.034), confirmed in multiple linear regressions after adjusting for steroid use. The overall individual variability of FeNO between time-points was 3.90 (2.53–7.29) ppb, with no significant difference in the distribution of FeNO values measured at different time-points (p = 0.204). A total of 28 (68.3%) patients exhibited FeNO always below the 25 ppb cut-off at all determinations, while the remining 13 (31.7%) had at least one value above the established limit. Interestingly, none of these 13 participants had FeNO stably above 25 ppb, all showing at least one normal value during serial sampling. Compared to these patients with more fluctuating values, the 28 with stably normal FeNO only exhibited a significantly higher body weight (80.0 ± 18.2 kg vs. 69.0 ± 8.8 kg, p = 0.013) and body mass index (29.7 ± 6.5 kg/m2 vs. 25.9 ± 3.7 kg/m2, p = 0.026), confirmed in multiple logistic regressions after adjusting for major potential confounders. Conclusions: A certain degree of FeNO variability, apparently unrelated to eosinophil counts but somehow influenced by body weight, must be considered in COPD patients. Further studies are needed to clarify whether this biomarker may be effectively used to plan more personalized pharmacological and rehabilitation strategies in this clinical setting. [ABSTRACT FROM AUTHOR]

The aim of the present study was to identify a cut-off of c-reactive protein (c-RP) potentially predictive of high-lethality suicide attempts (SA) in an inpatient psychiatric sample. After attempting suicide, subjects were admitted to the emergency ward of the IRCCS Ospedale Policlinico San Martino and later to the section of Psychiatry from 1 August 2013 to 31 July 2018. C-reactive protein was measured. The Area Under the Receiver Operating Characteristic (ROC_AUC) was used to assess the discriminative capacity of c-RP for high- vs. low-lethality SA, and a logistic regression was performed to detect the odds ratio, adjusted for age and sex. High-lethality suicide attempters were 133 (30.8%), while low-lethality suicide attempters were 299 (69.2%). The optimal cut-off threshold (and corresponding sensitivity and specificity values) for c-RP was 4.65 mg/L (68/71%). This cut-off corresponds to an AUC of 73.5%. An odds ratio of 4.70 was generated for current high-lethality SA after a logistic regression, adjusted for age and sex. Research on social and biological factors underlying the lethality of SA is crucial for a better understanding of this complex phenomenon. Identifying potential predictors of SA, especially those at high lethality, is essential to implement personalized preventive strategies. [ABSTRACT FROM AUTHOR]

Background: The criteria of the Diagnostic and Statistical Manual of Mental Disorders 5th edition "with mixed features specifier" (DSM‐5 MFS) are considered controversial since they include only typical manic symptoms. By contrast, Koukopoulos developed an alternative model of mixed depression (MxD) focusing primarily on the excitatory component. Objective: To compare DSM‐5 MFS and Koukopoulos' MxD (KMxD) in terms of prevalence, associated clinical variables, and discriminative capacity for bipolar depression in patients with major depressive episode (MDE). Methods: A total of 300 patients with MDE—155 with major depressive disorder and 145 with bipolar disorder (BD)—were recruited. The discriminative capacity of DSM‐5 MFS and KMxD criteria for BD was estimated using the area under the curves of receiver operating characteristic (ROC_AUC). The clinical variables associated with these two diagnostic constructs were assessed by performing a logistic regression. Results: A total of 44 and 165 patients met the DSM‐5 MFS and KMxD criteria, respectively. The ROC_AUCs and their confidence intervals for BD according to DSM‐5 MFS and KMxD were 77.0% (72.0%‐82.1%) and 71.9% (66.2%‐77.7%), respectively. The optimal thresholds (combining sensitivity and specificity measures) for BD diagnosis were ≥1 (77%/68%) for DSM‐5 MFS and ≥3 symptoms (78%/66%) for KMxD. However, considering the DSM‐5 MFS cut‐off (≥3 symptoms), the specificity (97%) increased at the expense of sensitivity (26%). Conclusions: KMxD and DSM‐5‐MFS showed an overlapping discriminative capacity for bipolar depression. The current diagnostic threshold of DSM‐5 MFS did not prove to be very inclusive, if compared with the greater diagnostic sensitivity of KMxD, which also yielded better association with clinical variables related to mixedness. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluates if the addition of a curcumin formulation with a polyvinylpyrrolidone-hydrophilic carrier (CHC; Diabec®, Alfa Intes, Italy) to intravitreal injections of dexamethasone (DEX-IVT) can affect the morphological retinal characteristics, extending the steroid re-treatment period in patients with diabetic macular edema (DME). Methods: A randomized controlled clinical trial was carried out in DME patients, randomly assigned to receive DEX-IVT or DEX-IVT and a CHC. The evaluation of the mean difference of central retinal thickness (CRT) was the primary aim. Secondary aims were the evaluations of best-corrected visual acuity, differences in the predetermined retinal layer thickness, the number/time of re-treatment, and the assessment of safety. Results: A total of 73 DME patients were included (35 in the control group and 38 in the combined therapy group). In both the control and combined therapy groups, the mean CRT change from T0 to the 6 months' evaluation was significant (p = 0.00). The mean CRT result was significantly different at month 4 (p = 0.01) between the control and combined therapy groups, with a greater reduction in the combined therapy group, in particular, in patients with ≤10 years of diabetes. A trend of CRT reduction in the combined therapy group has been observed also considering patients with subfoveal neuroretinal detachment. In addition, we observed that the reduction of inner retinal layer thickness was greater in the combination group, in comparison with controls. Conclusion: The combination of a CHC to DEX-IVT is a promising therapeutic option in case of DME, in particular, for patients with early-stage diabetes and with an inflammatory phenotype. Further studies will be necessary to confirm these findings. [ABSTRACT FROM AUTHOR]

Objectives: Upper urinary tract urothelial carcinoma (UTUC) represents about 5–10% of all urothelial malignancies with an increasing incidence. The standard diagnostic tools for the detection of UTUC are cytology, computed tomography (CT) urography, and ureterorenoscopy (URS). No biomarker to be included in the daily clinical practice has yet been identified. The aim of our study was to evaluate the potential role of Xpert® Bladder-Cancer (BC)-Detection in the diagnosis of UTUC. Methods: Eighty-two patients underwent 111 URS with Xpert® BC-Detection, cytology, or Urovysion® analysis of UT for suspicion of UTUC. Twenty-four cases were excluded from the analysis due to a non-diagnostic Xpert® BC-Detection, cytology, or Urovysion®. Samples were analyzed with upper tract (UT) urinary cytology, with Xpert® BC-Detection on UT urines, and with Urovysion® Fluorescence in situ hybridization (FISH) test. After urine collection, the patients underwent retrograde pyelography and/or URS, and if positive a UT biopsy. The Xpert® BC-Detection was reported by the software as negative or positive [cut-off total Linear Discriminant Analysis (LDA) = 0.45]. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of cytology, Xpert® BC-Detection and Urovysion-FISH were calculated using URS and/or histology results as reference. Results: In all, 27 (31%) of 87 URS resulted positive, with 20 low-grade (LG) and 7 high-grade (HG) tumors. Overall sensitivity was 51.9% for cytology, 100% for Xpert® BC-Detection, and 92.6% for Urovysion. The sensitivity of cytology increased from 26% in LG to 100% in HG tumors. For Xpert® BC-Detection, sensitivity was 100% both in LG and in HG, and for Urovysion-FISH, it increased from 90% in LG to 100% in HG tumors. PPV was 82.4% for cytology, 35% for Xpert® BC-Detection, and 73.5% for Urovysion. NPV was 81.4% for cytology, 100% for Xpert® BC-Detection, and 96.2% for Urovysion. Conclusion: The excellent NPV of Xpert® BC-Detection allows to avoid unnecessary endoscopic exploration of the UT, reducing invasiveness and URS complications in the follow-up of UTUC. [ABSTRACT FROM AUTHOR]

Background. Subthreshold hypomania during a major depressive episode challenges the bipolar-unipolar dichotomy. In our study we employed a cross-diagnostic cluster analysis - to identify distinct subgroups within a cohort of depressed patients. Methods. A k-means cluster analysis— based on the domain scores of the Mood Spectrum Self-Report (MOODS-SR) questionnaire—was performed on a data set of 300 adults with either bipolar or unipolar depression. After identifying groups, between-clusters comparisons were conducted on MOODS-SR domains and factors and on a set of sociodemographic, clinical and psychometric variables. Results. Three clusters were identified: one with intermediate depressive and poor manic symptomatology (Mild), one with severe depressive and poor manic symptomatology (Moderate), and a third one with severe depressive and intermediate manic symptomatology (Mixed). Across the clusters, bipolar patients were significantly less represented in the Mild one, while the DSM-5 “Mixed features”specifier did not differentiate the groups. When compared to the other patients, those of Mixed cluster exhibited a stronger association with most of the illness-severity, quality of life, and outcomes measures considered. After performing pairwise comparisons significant differences between “Mixed” and “Moderate” clusters were restricted to: current and disease-onset age, psychotic ideation, suicidal attempts, hospitalization numbers, impulsivity levels and comorbidity for Cluster B personality disorder. Conclusions. In the present study, a clustering approach based on a spectrum exploration of mood symptomatology led to the identification of three transdiagnostic groups of patients. Consistent with our hypothesis, the magnitude of subthreshold (hypo)manic symptoms was related to a greater clinical severity, regardless of the main categorical diagnosis. [ABSTRACT FROM AUTHOR]

Background. Chronic cough is a disabling condition with a high proportion of diagnostic and therapeutic failures. Fractional exhaled nitric oxide (FeNO) has been considered a useful biomarker for predicting inhaled corticosteroids (ICS) response. We evaluated the relationship between FeNO and ICS response in chronic cough by performing a systematic review with meta-analysis. Methods. PubMed, Web of Science, Scopus and EMBASE databases were systematically searched. Differences were expressed as Odds Ratio (OR) with 95% confidence intervals (95%CI). Pooled sensitivity, specificity, positive (PLR) and negative likelihood ratio (NLR), and area under the hierarchical summary receiver operating characteristic curve (HSROCAUC) were estimated. Results. Nine articles on 740 chronic-cough patients showed that the response rate to ICS was 87.4% (95%CI: 83.8–91.0) in 317 patients with a high FeNO and 46.3% (95%CI: 41.6–51.0) in 423 controls, with an attributable proportion of 47.0% and a diagnostic OR of 9.1 (95%CI: 3.7–22.4, p <.001). The pooled estimate of diagnostic indexes resulted in a sensitivity of 68.5% (95%CI: 46.7–84.4) and specificity of 81.9% (95%CI: 63.0–92.3), with a HSROCAUC of 0.82 (95%CI: 0.64–0.90). In a realistic scenario with a pre-test probability set at 30%, based on a pooled PLR of 3.79 (95%CI: 1.24–7.47) and NLR of 0.38 (95%CI: 0.22–0.66), the post-test probability was 62% with a high FeNO and 14% if the test was negative. Subgroup analyses confirmed a better performance for the recommended FeNO cut-off greater than 25 ppb. Meta-regression and sensitivity analyses showed no impact of major demographic and clinic variables on results. Conclusions. A high FeNO before starting ICS therapy may help identify chronic-cough patients responding to treatment, with a better performance ofhigher cut-off values. Further studies are needed to evaluate the real usefulness of this biomarker to guide cough therapy and optimise strategies in different healthcare settings (community, hospital, rehabilitation). Chronic cough is a disabling condition with a high proportion of diagnostic and therapeutic failures. Fractional exhaled nitric oxide (FeNO) may be a useful biomarker for identifying chronic cough patients who respond to steroid treatment. A FeNO cut-off lower than 25 ppb should be considered irrelevant for this clinical application. [ABSTRACT FROM AUTHOR]

To compare the degree of accuracy of the Face Hunter facial scanner and the Dental Pro application for facial scanning, with respect to both manual measurements and each other. Twenty-five patients were measured manually and scanned using each device. Six reference markers were placed on each subject's face at the cephalometric points Tr, Na′, Prn, Pog′, and L–R Zyg. Digital measurement software was used to calculate the distances between the cephalometric reference points on each of the scans. Geomagic X Control was used to superimpose the scans, automatically determining the best-fit alignment and calculating the percentage of overlapping surfaces within the tolerance ranges. Individual comparisons of the four distances measured anthropometrically and on the scans yielded an intraclass correlation coefficient index greater than.9. The t-test for matched samples yielded a P value below the significance threshold. Right and left cheeks reached around 60% of the surface, with a margin of error between 0.5 mm and −0.5 mm. The forehead was the only area in which most of the surface fell within the poorly reproducible range, presenting values out of tolerance of more than 20%. Three-dimensional scans of the facial surface provide an excellent analytical tool for clinical evaluation; it does not appear that one or the other of the measuring tools is systematically more accurate, and the cheeks are the area with the highest average percentage of surface in the highly reproducible range. [ABSTRACT FROM AUTHOR]

Background: Endothelial dysfunction is a key mechanism in the development of cardiac remodelling and diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF). Flow‐mediated (FMD) and nitrate‐mediated dilation (NMD) are noninvasive methods to assess endothelial function. We performed a meta‐analysis evaluating the impact of HFpEF on FMD and NMD. Methods: PubMed, Web of Science, Scopus and EMBASE databases were systematically searched according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Differences were expressed as mean difference (MD) with 95% confidence intervals (95%CI). The random effects method was used. Results: A total of seven studies were included in the final analysis, 7 with data on FMD (326 HFpEF patients and 417 controls) and 3 on NMD (185 HFpEF patients and 271 controls). Compared to controls, HFpEF patients showed significantly lower FMD (MD: −1.929; 95%CI: −2.770, −1.088; P <.0001) and NMD values (MD: −2.795; 95%CI: −3.876, −1.715; P <.0001). Sensitivity analyses substantially confirmed results. Meta‐regression models showed that increasing differences in E/A ratio (Z‐score: −2.002; P =.045), E/E' ratio (Z‐score: −2.181; P =.029) and left atrial diameter (Z‐score: −1.951; P =.050) were linked to higher differences in FMD values between cases and controls. Conclusions: Impaired endothelial function can be documented in HFpEF, with the possibility of a direct association between the severity of diastolic and endothelial dysfunction. Targeting endothelial dysfunction through pharmacological and rehabilitation strategies may represent an attractive therapeutic option. [ABSTRACT FROM AUTHOR]

Objective: To verify the existence of a correlation between the mesio-distal size of teeth and the arch width by analyzing the data separately for maxillary and mandibular arch in patients with ideal occlusion. Material and Methods: 58 patients with ideal occlusion were studied, for a total of 276 files analyzed. Dental casts were then scanned using a professional scanner (Epson Perfection v 330) and images were obtained in TIFF format at 600 dpi. All single teeth measurements were carried out for all teeth of both arches using the VAM software (Vectra, Canfield Scientific, Fairfield, NJ, USA). The repeatability and reproducibility of the measurement method were evaluated using the Gauge R&R method. In case a correlation between tooth size and arch size is found to be significant, a linear regression analysis can be applied through the following statistical relationship: y=a+b*x, where y is the result (inter-molar distance "AvgB66" or inter-canine distance "Cusp 33"), and x the specific tooth. The a and b respectively represent the intercept (point of intersection between the line and the y axis) and the slope of the line that describes the regression ratio. Results: The statistical analysis highlights a significant correlation (p<1%) between the results of the mesio-distal measurements of each tooth and the two variables considered to define the size of each arch ("AvgB66" and "Cusp 33"). Based on these results, a numerical relationship "y=a+b*x" has been extrapolated. Thus, it is possible to calculate the estimated inter-molar or inter canine distance necessary to have the teeth aligned. Conclusion: The inter-canine and inter-molar distances can be estimated starting from measuring the mesio-distal diameter of a single tooth. [ABSTRACT FROM AUTHOR]

Objective: To obtain reference values for tip, torque and in-out from digital models of Italian and Mozambican subjects in ideal occlusion using a repeatable and validated method and to compare these measurements with previously reported values. Material and Methods: Dental parameters were acquired from digital models of each subject, categorized to one of two groups: Italians (23 males, 27 females; mean age 28.3 years, ±5.7 years) and Mozambicans (14 males, 15 females; mean age, 23.4 years, ±5.9), using VAM software. All subjects had ideal occlusion, permanent dentition and no previous orthodontic treatment, fillings or prostheses. After normality of data was assumed (p<0.05), a paired t-test was performed to detect any statistical differences between the two groups (p<0.05). Then, classical inference (ttest and power analysis) was used to compare our data to those reported by other authors. Results: Mozambicans' incisors were more proclined, while their upper molars appeared to be more prominent regarding Italians'. Italians shown greater tip values, especially at the upper first premolars and lower first molars. In-out values were comparable between the two groups, except for the upper molars (more prominent in Mozambicans) and lower first molar (more prominent in Italians). Unlike other reports, upper second molars displayed negative tip in our samples. Conclusion: Pre-adjusted appliances with standard prescription should not be expected to guarantee optimal outcomes. Prescriptions specific for ethnicities are recommended and reference values should be reconsidered. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of passive self-ligating appliances (PSLAs) and conventional ligating appliances (CLAs) during orthodontic treatment regarding torque, tip, and transversal dental changes. Material and Methods: Dental parameters were digitally acquired from pre- and post-treatment models of each subject belonging to two groups of patients treated with PSLAs (23 patients; 11 females and 12 males with a mean age of 14.2 ± 1.6 years) and CLAs (18 patients; 10 females and 8 males with a mean age of 14.3 ± 1.9 years), respectively. All subjects had Class I or slight Class II malocclusion (= 2mm), permanent dentition and no previous orthodontic treatment. After normality of data was assumed, a paired sample ttest rejected any side differences at T0 and, therefore, the data were grouped by tooth group. Statistical analyses were performed using a linear mixed-effect framework, assuming the appliance, time, and interactions as fixed effects and the tooth type as random effects. Finally, post-hoc effect analysis was used to contrast modeled marginal effects (p<0.05). Results: For both appliances, there is a general increase of both torque and transverse values at T1, especially for PSLAs. Tip shows a general reduction in the lateral sectors for both appliances is registered. The only significant statistical difference referred to appliances' efficacy is located to mandibular intermolar width. Conclusion: Both appliances have an expansive potential for both torque and transverse dental changes. No evident differences are detectable between appliances except for the rate of the mandibular intermolar width increase. [ABSTRACT FROM AUTHOR]

Objective: To evaluate how the lower arch spontaneously change after upper rapid palatal expansion in a group of patients with transversal skeletal deficit. Material and Methods: Twenty-four patients treated by the same orthodontist with a rapid palatal expander (RPE) bounded on a deciduous molar have been selected. The sample was divided into two groups: no treatment was provided for group one, while group two was treated using a lip bumper or Schwarz appliance. For each patient, dental casts were collected when the RPE was bounded (T0) and at the end of treatment, 9 months ± 3 months later (T1). Each outcome was analyzed, providing descriptive statistics, main effects significance tests and post-hoc analyses with the objective to evaluate the variations between pre-treatment (TO) and post-treatment (T1) of each of them. Results: If the linear measurements are considered, a significant beneficial effect on both arches is observed. However, the upper arch always shows a major increase of all values at T1 with respect to the lower arch. Even though the post-hoc tables indicate that time differences are all statistically significant across considered partitions, the lower arch's increase is more pronounced in group two, where patients were treated in both arches. If the angular measurements are concerned, the increase of lingual crown inclination was found in all patients, independently from the type of treatment in lower arch. Conclusion: All patients show normalization of upper diameters, regardless of whether the lower arch was treated or not. [ABSTRACT FROM AUTHOR]

Aims: Xpert® Bladder Cancer Monitor is a urinary marker based on the evaluation of five target mRNAs overexpressed in patients with bladder cancer (BC). The aim of our study is to update our results regarding the diagnostic accuracy of the Xpert® Bladder Cancer Monitor test in the follow-up of patients with non-muscle invasive bladder cancer (NMIBC). Methods: We conducted a prospective study on 1015 samples of 416 patients (mean age 72.2 ± 10.3 years) under follow-up for NMIBC. Patients underwent voided urinary cytology, the Xpert® Bladder Cancer Monitor test and cystoscopy and, if positive, a transurethral resection of the bladder. Xpert® Bladder Cancer Monitor was reported as negative or positive: cut-off total Linear Discriminant Analysis (LDA) = 0.5. Results: We identified 168 recurrent tumours: 126 (75%) were low-grade (LG) and 42 (25%) high-grade (HG). Overall sensitivity was 17.9% for cytology, 52.4% for Xpert® Bladder Cancer Monitor and 54.2% for the two tests combined. The sensitivity of cytology increased from 6.3% in LG to 52.4% in HG tumours whereas Xpert® Bladder Cancer Monitor showed a sensitivity ranging from 42.9% in LG to 80.9% in HG tumours. Combined cytology and Xpert® Bladder Cancer Monitor yielded an overall sensitivity of 45.2% for LG and 80.9% for HG tumours. Overall specificity was 98.5% for cytology and 78.4% for Xpert® Bladder Cancer Monitor and 78.2% for the two tests combined. The area under the curve (AUC) for Xpert® Bladder Cancer Monitor was 0.71; stratifying the patients according to the European Association of Urology risk groups, the AUC was 0.69, 0.67 and 0.85 for low, intermediate and high risk, respectively (p = 0.0003). Conclusion: Our data confirm a significantly higher sensitivity of Xpert® Bladder Cancer Monitor than for cytology in a larger patient cohort. The test performed very well in terms of specificity but could not reach the high value of cytology. Along with voided urinary cytology the test could allow to reduce cystoscopies in follow-up patients, reducing discomfort to the patients and costs. [ABSTRACT FROM AUTHOR]

BACKGROUND: The objective of the current study was to compare the diagnostic accuracy of 2 new real-time polymerase chain reaction--based urinary markers with each other and with urinary cytology, cystoscopy, and/or histology in patients being followed for non--muscle-invasive bladder cancer. METHODS: A total of 487 patients were enrolled in the study. Patients were evaluated using voided urine cytology, the Xpert Bladder Cancer Monitor, the Bladder EpiCheck test, and white light cystoscopy. RESULTS: The overall sensitivity was 27.17% for cytology, 64.13% for the Bladder EpiCheck test, and 66.3% for the Xpert Bladder Cancer Monitor. The overall specificity was 98.82% for cytology, 82.06% for the Bladder EpiCheck test, and 76.47% for the Xpert Bladder Cancer Monitor. The negative predictive value was very similar for the 3 tests at 83.56% for cytology, 89.42% for the Bladder EpiCheck test, and 89.35% for the Xpert Bladder Cancer Monitor. When combined, the Bladder EpiCheck test and Xpert Bladder Cancer Monitor detected overall 79.35% of the tumors: 70.37% in low-grade and 92.11% in high-grade tumors. CONCLUSIONS: The Xpert Bladder Cancer Monitor and Bladder EpiCheck test were found to perform very well in terms of sensitivity. Together, the 2 tests detected approximately 92.11% of high-grade tumors. Their specificity was high but could not reach the excellent value of cytology. The negative predictive value was the same for both tests and was higher than that for cytology, especially when the tests were used together (92.24%). These 2 new tests hold promise as urinary biomarkers. They may be used in combination to maximize sensitivity in a less invasive way, thereby reducing invasiveness in the follow-up of patients with non--muscle-invasive bladder cancer and decreasing discomfort for the patients as well as complications and costs. [ABSTRACT FROM AUTHOR]

The markovchain package aims to provide S4 classes and methods to easily handle Discrete Time Markov Chains (DTMCs), filling the gap with what is currently available in the CRAN repository. In this work, I provide an exhaustive description of the main functions included in the package, as well as hands-on examples. [ABSTRACT FROM AUTHOR]

Objective: To assess the agreement between adolescents and their parents/caregivers regarding the impact of malocclusion on adolescents' oral health-related quality of life (OHRQoL). Materials and Methods: A consecutive sample of 141 adolescent and parent/caregiver pairs was selected. Adolescents answered the short version of the Child Perceptions Questionnaire (CPQ11-14), while parents answered the Parental-Caregiver Perceptions Questionnaire (P-CPQ). The CPQ11-14 and the P-CPQ have 14 items in common that are organized through four subscales: oral symptoms (OS), functional limitations (FL), emotional well-being (EW), and social well-being (SW). Agreement on the overall score and agreement on the subscales were determined using comparison and correlation analysis. The comparison analysis was carried out by comparing the mean directional and absolute differences, and the correlation analysis was performed using the intraclass correlation coefficient (ICC). Results: A total of 135 pairs of adolescents and parents/caregivers agreed to answer the questionnaires, providing a response rate of 95.7%. The mean age of the adolescents was 11.50 years. The mean directional difference was significant for the OS (P < .001) and FL (P?=?.040) subscales as well as for the overall score (P?=?.007). Adolescents' reports were higher than parents/caregivers' reports. The mean absolute difference for the overall score was 7.26, representing 12.9% of the maximum possible overall score. The ICC was 0.16 for the overall score, indicating poor agreement. Conclusion: Poor agreement was observed between adolescents and their parents/caregivers in rating the impact of malocclusion on adolescents' OHRQoL. [ABSTRACT FROM AUTHOR]