Suitability and Usefulness of a Flexible Dosing Timing of Oral Semaglutide to Maximize Benefit in Clinical Practice: An Expert Panel.

From clinical trials and observational data, oral semaglutide has proven to be the most effective second-line oral therapy for the management of patients with type 2 diabetes. This review aims to describe the perspective of an Italian expert panel that addressed the potential challenges arising during the use of oral semaglutide in the free-living conditions of routine clinical care. A group of Italian experts discussed and generated insights into the use of oral semaglutide in clinical practice. Key topics included the effectiveness of oral semaglutide in clinical practice, the positioning of the agent to optimize the treatment benefits, the possibility to adopt flexibility in the administration schedule, critical issues encountered, the role of patient communication and information in the importance of dose escalation and management of adverse events. Available data on efficacy and effectiveness of oral semaglutide from randomized clinical trials and real-world studies were reported, along with factors that determine tolerability and persistence on treatment. The debate over a fixed versus a flexible dosing schedule was critically addressed, providing anecdotical clues from a small case series and a real-world database. Additionally, a set of recommendations for clinicians to consider when prescribing oral semaglutide and during the process of patient monitoring were provided.

Urban diabetes: analysis of diabetes prevalence in cities of the Lombardy region participating in the cities changing diabetes project.

AIM: The urban population increases by about 60 million people/year. Urbanization, unhealthy lifestyle and aging of the population are reflected in a constant growth in the prevalence of diabetes. In 2014, Steno Diabetes Centre in Copenhagen, University College London and Novo Nordisk, launched the Cities Changing Diabetes® program with the aim of creating a unified movement that would stimulate policy-makers to prioritize urban diabetes. METHODS: The socio-demographic data derive from (1) ISTAT (National Institute of Statistics of Italy), (2) ATS Metropolitan City of Milan, (3) ATS Val Padana-Cremona, (4) ATS Insubria-Varese, (5) The unemployment rates of the various municipalities have been extrapolated from an ISTAT-MEF elaboration published by Sole 24 Ore journal. RESULTS: In the different sanitary districts of the Metropolitan City of Milan, a strong linear correlation was found between the prevalence of diabetes and the prevalence of heart disease (R = 0.695, p < 0.001), as well as between the prevalence of diabetes and of nephropathies (R = 0.316, p < 0.001). The analysis concerning the province of Cremona showed a fair correlation between the prevalence of diabetes and cardiovascular disease (R = 0.658, p < 0.001). Even for the municipalities of Varese, the analysis documented a good correlation between the prevalence of diabetes and heart disease (R = 0.419, p < 0.001), but not between diabetes and nephropathies. CONCLUSIONS: Interesting differences in the relationship of diabetes prevalence with several diseases and socio-demographic factors have been found when comparing the metropolitan City of Milan with two smaller size cities as Varese and Cremona. Our present data confirm the hypothesis that urban diabetes will be the challenge for our society during the next decades.

Cyclic Fatigue Resistance of Rotary versus Reciprocating Endodontic Files: A Systematic Review and Meta-Analysis.

(1) Background: The failure of nickel-titanium (NiTi) rotary files is a complication related to endodontic instruments. The aim of this study was to compare the resistance to cyclic fatigue between rotary and reciprocating file systems. (2) Methods: Specific PICO: Population (P): artificial root canals; Interventions (I): instrumentation with NiTi rotary and reciprocating files; Comparison (C): rotary versus reciprocating files; Outcome (O): cyclic fatigue resistance. Studies were identified through bibliographic research using electronic databases (Medline, Embase, Scopus, SciELO, and WOS). The studies were combined using a random effects model by the inverse variance method. The effect size was the mean of the time to fracture (TTF) and number of cycles to fracture (NCF). Heterogeneity was assessed using the p value of the Q test for heterogeneity and the I2. (3) Results: TTF for rotary files was determined in 474.5 s and 839.1 for reciprocating without statistically significant differences. NCF for rotary systems was determined in 1444.2 and for reciprocating file systems in 4155.9 with statistically significant differences (p = 0.035), making reciprocating files more resistant. (4) Conclusions: Reciprocating files have better resistance to cyclic fatigue than rotary files. When tested in double curvature canals, reciprocating files also showed higher resistance.

Mandibular third molar extraction: perceived surgical difficulty in relation to professional training.

BACKGROUND: Establishing the level of surgical difficulty pre-operatively is an essential step in ensuring correct treatment planning. This study set out to determine whether the knowledge and experience acquired by dentists who had received different levels of training influenced, firstly, the perceived levels of difficulty of a variety of cases of mandibular third molar (MTM) extraction and, secondly, the perceived difficulty deriving from a series of factors (patient-related factors, anatomical and radiographic factors, operative factors). METHODS: This cross-sectional, descriptive, observational study took the form of a survey. Using a visual analog scale (VAS), participants evaluated both the perceived difficulty of 30 cases of MTM extraction described by means of digital panoramic radiographs and the perceived difficulty deriving from a series of factors conditioning MTM extraction. The results underwent statistical analysis with SPSS Statistics 28.0 software. Non-parametric tests (Mann Whitney test for independent samples and the Kruskal-Wallis test) were applied. RESULTS: A total of 389 surveys were available for analysis. Dental practioners with no surgical training saw the intervention as presenting greater difficulty. Professionals with postgraduate training in oral surgery considered patient-related factors more important than operative factors, in contrast to dentists who had not received oral surgery training. CONCLUSIONS: Dental training has a signficant influence on the perceived difficulty of MTM extraction and also affects opinions about which factors have greater or lesser influence on surgical difficulty.

Analysis of the Importance of the Motion Used in the Resistance of Different Mechanical Instrumentation Systems in Endodontics: A Comparative Study.

Aim: The aim of this study was to compare the cyclic fatigue strength of different reciprocating rotary systems depending on the movement used. Methods: Four study groups were analyzed (n = 30): (1) Reciproc®, (2) Reciproc Blue®, (3) Wave One Gold® and (4) Procodile®. Each group was divided into three subgroups according to the motion used: (A) Reflex Dynamic® (n = 10), (B) ReFlex Smart® (n = 10) and (C) conventional reciprocating motion (n = 10). They were used in a dynamic cyclic fatigue prototype until their fracture, and the time was measured in seconds. The results obtained were analyzed with the ANOVA method, and for two-to-two comparisons, the Tukey method and Weibull statistics were used. Results: Procodile ReFlex Smart had the longest time to failure, and statistically significant differences were found between Procodile ReFlex Smart and the other files and motions (p < 0.05). Conclusion: Smart motions increase cyclic fatigue strength. ReFlex Smart® motion increases the cyclic fatigue strength of reciprocating rotary systems, and Procodile® ReFlex Smart was the most resistant system file.

Real world effectiveness of subcutaneous semaglutide in type 2 diabetes: A retrospective, cohort study (Sema-MiDiab01).

Introduction: Aim of the present study was to evaluate the real-world impact of once-weekly (OW) subcutaneous semaglutide on different end-points indicative of metabolic control, cardiovascular risk factors, and beta-cell function in type 2 diabetes (T2D). Methods: This was a retrospective, observational study conducted in 5 diabetes clinics in Italy. Changes in HbA1c, fasting blood glucose (FBG), body weight, blood pressure, lipid profile, renal function, and beta-cell function (HOMA-B) during 12 months were evaluated. Results: Overall, 594 patients (97% GLP-1RA naïve) were identified (mean age 63.9 ± 9.5 years, 58.7% men, diabetes duration 11.4 ± 8.0 years). After 6 months of treatment with OW semaglutide, HbA1c levels were reduced by 0.90%, FBG by 26 mg/dl, and body weight by 3.43 kg. Systolic blood pressure, total and LDL-cholesterol significantly improved. Benefits were sustained at 12 months. Renal safety was documented. HOMA-B increased from 40.2% to 57.8% after 6 months (p<0.0001). Discussion: The study highlighted benefits of semaglutide on metabolic control, multiple CV risk factors, and renal safety in the real-world. Semaglutide seems to be an advisable option for preservation of ß-cell function and early evidence suggests it might have a role in modifying insulin resistance (HOMA-IR), the pathogenetic basis of prediabetes and T2D.

Adding Two Antimicrobial Glasses to an Endodontic Sealer to Prevent Bacterial Root Canal Reinfection: An In Vivo Pilot Study in Dogs.

Current endodontic procedures continue to be unsuccessful for completely removing pathogens present inside the root canal system, which can lead to recurrent infections. In this study, we aimed to assess the antimicrobial capacity and tissue response of two inorganic bactericidal additives incorporated into a paste root canal sealer on contaminated root dentin in vivo. An experimental study was performed in 30 teeth of five Beagle dogs. After inducing microbiological contamination, root canal systems were treated by randomly incorporating one of two antimicrobial additives into a commercial epoxy-amine resin sealer (AH Plus), i.e., G3T glass-ceramic (n = 10) and ZnO-enriched glass (n = 10); 10 samples were randomized as a control group. After having sacrificed the animals, microbiological, radiological, and histological analyses were performed, which were complemented with an in vitro bactericidal test and characterization by field emission scanning electron microscopy. The tested groups demonstrated a non-significant microbiological reduction in the postmortem periapical index values between the control group and the bactericidal glass-ceramic group (p = 0.885), and between the control group and the ZnO-enriched glass group (p = 0.169). The histological results showed low values of inflammatory infiltrate, and a healing pattern characterized by fibrosis in 44.4% of the G3T glass-ceramic and 60.0% of ZnO-enriched glass. Bactericidal glassy additives incorporated in this root canal sealer are safe and effective in bacterial reduction.

A Comparative Study of Biocompatibility in Rat Connective Tissue of a New Mineral Trioxide Compound (Theracal) versus MTA and a Bioactive G3 Glass.

The aim of this paper was to assess the differences in tissue response to implantation during 15, 30 and 45 days in the subcutaneous connective tissue of Wistar rats from three biomaterials: Angelus MTA®, Theracal LC®, and Angelus MTA® to which 25% bioglass G3 was added. Twenty-four Wistar rats were used, the materials were inserted into the rat's dorsal area in silicone tubes 5 mm long by 1.5 mm diameter. Histological reaction was assessed at 15, 30, and 45 days after implantation. They were then stained with hematoxylin eosin and evaluated by two observers. Data were analyzed using Fisher's exact test and Mann-Whitney's U test was used to determine the association between variables. Angelus MTA induced the formation of dystrophic calcifications twice as much as Theracal LC (p < 0.05). The addition of G3 did not affect the greater or lesser occurrence of calcifications (p > 0.05). Theracal LC and MTA plus G3 caused an inflammatory reaction, which was chronic at 15 days and decreased in intensity, almost disappearing after 45 days. Theracal LC, as well as Angelus MTA plus G3, were well tolerated when implanted in the subcutaneous connective tissue of rat. Histologically, no inconvenience was found for the use by direct contact of Theracal LC, and the mixture of MTA with 25% bioactive glass G3, in the tissue of Wistar rats.

Photodynamic therapy in endodontic root canal treatment significantly increases bacterial clearance, preventing apical periodontitis.

OBJECTIVE: To analyze the antimicrobial activity of photodynamic therapy as an adjunct to conventional endodontic treatment, particularly against Enterococcus faecalis. METHOD AND MATERIALS: A total of 42 single-rooted teeth obtained from 33 patients with apical periodontitis were included. Sampling was developed in three stages: (1) immediately after accessing the root canal, (2) after chemical and mechanical instrumentation, and finally, (3) after photodynamic therapy application. The bacterial load of each sample was quantified by seeding on blood agar plates and selective M-Enterococcus agar. All growing colonies were identified using MALDI-TOF (Bruker; matrix-assisted laser desorption/ionization time-of-flight), and the entire bacterial microbiota composition was determined in the first sample by PCR-DGGE (polymerase chain reaction denaturing gradient gel electrophoresis), using 16 rDNA primers and selective nucleotide sequencing. RESULTS: The endodontic therapy obtained a mean reduction in the cultivable bacterial load of 1.12 log, whereas the photodynamic therapy combination significantly increased the bacterial clearance (P < .0001). Viable cells of E faecalis were detected in 16.6% of root canals, with a mean value of 93 CFU per tooth, which was reduced to 67 and 9 CFU/tooth after conventional endodontic and photodynamic therapy treatments, respectively. Molecular E faecalis detection demonstrated that this species was present in 23.2% of baseline samples. DGGE analysis demonstrated the existence of a more complex microbiota than those observed using classical cultures. CONCLUSION: Photodynamic therapy as an adjunct to root canal treatment produces a significant reduction in E faecalis bacterial load, and it should be considered in the prevention of apical periodontitis.

Endodontic re-treatment and restorative treatment of a dens invaginatus type II through new technologies.

BACKGROUND: The complex anatomy of dens invaginatus makes access cavity to root canal system difficult, which has an impact on the prognosis of these teeth. A novel technique, based on new technologies, is proposed to make access cavity conservative and guided with minimal dental structure lost. MATERIAL AND METHODS: This case report shows the root canal retreatment and the endodontic surgery of a dens invaginatus type II in a left lateral upper incisor previously treated which was affected by a chronic apical abscess and an apical fracture. A Cone Beam Computed Tomography was performed to better diagnosis the dental anatomy. An intraoral scan was performed to get a digital 3D model. A computer-guided implant planning software was used to plan the access cavity and design the splint guided. Finally, the clinical crown was restored by a resin nanoceramic veneer made by a chairside system made up of an intraoral scanning unit and a grinding unit. Last, the authors carried through the endodontic surgery to extract the apical fractured fragment. RESULTS: Follow-up appointments at 6, 12 and 18 months showed a radiographic reduction of the periapical lesion and absence of clinical signs. CONCLUSIONS: The splint guide allowed a guided and conservative access cavity to root canal system. It facilitates the root canal retreatment and improves the prognosis of the teeth with dental malformations. Key words:CAD-CAM, Cone-Beam Computed Tomography, dens in dente, dens invaginatus, dental pulp cavity, endodontics.

Histological analysis of different local haemostatic agents used for periapical surgery: An experimental study with Sprague-Dawley rats.

The aim of the present study was to analyse differences in the tissue response to the different haemostatic agents used for periapical surgery (BloodSTOP iX® (oxicellulose), Expazen® (aluminum chloride), calcium sulphate (CS), Gelatamp® (gelatin sponge) and Hemocor® (ferric sulphate). Seventy-two bone defects were made on the calvarium of 36 Sprague-Dawley rats. The specimens were euthanised at 3, 6 and 12 weeks. Histological analysis revealed a giant cell foreign body reaction against BloodStop iX® , Gelatamp® and Hemocor® . Leukocytes persisted at the surgical bed during the healing process longer as expected with Gelatamp® (6 weeks) and Hemocor® (12 weeks). We confirmed a generalised delay in bone formation. Calcium sulphate did not cause any foreign body reaction. CS showed excellent results with a high degree of compatibility, there was no inflammatory reaction with this agent after 12 weeks and was not associated with a significant foreign body reaction at any time during the study.

Endodontic treatment of dens evaginatus by performing a splint guided access cavity.

AIM: Dens evaginatus (DE) is described as an unusual dental malformation. Tooth structure variations attached to this anatomical disturbance complicates the performance of a conservative access cavity for a conventional root canal treatment. Author's purpose is to describe the treatment of a type V DE by using splits as guides to perform access cavity. CLINICAL CONSIDERATIONS: This clinical case shows a root canal treatment of a type V DE diagnosed by using a cone beam computed tomography (CBCT). Access cavity was planned through an osseointegrated implant planning software and guided by a stereolithographied split. After endodontic treatment, tooth was sculpted for placing a veneer, processed by a chair-side system in a single session. CONCLUSIONS: CBCT is an effective method for obtaining internal anatomical information of teeth with anatomical malformations. The osseointegrated implant planning software is an effective method for planning root canal treatment and designing stereolithograped splits (for performing minimally invasive access cavities). CLINICAL SIGNIFICANCE: Stereolithographed splints allow performing a guided and conservative access cavity of teeth affected by dental malformations whereas digital technology allows us to esthetically reconstruct a tooth in a single session.

An analysis in vivo of intracanal bacterial load before and after chemo-mechanical preparation: A comparative analysis of two irrigants and two activation techniques.

BACKGROUND: The goals of this randomized double-blind trial were to assess the antimicrobial activity in vivo of Sodium hypochlorite (NaOCl) vs. chlorhexidine gluconate (CHX) used in combination either with EndoActivator® or IRRI S® files in patients with apical periodontitis. MATERIAL AND METHODS: A total of 120 patients with apical periodontitis (in single or multiple root canals) were randomly assigned to the four irrigation protocols outlined below: Group A: 5.25% sodium hypochlorite (NaOCl) + EndoActivator®; Group B: 5.25% NaOCl + IRRI S® files; Group C: 2% chlorhexidine gluconate (CHX) + EndoActivator®; Group D: 2% CHX + IRRI S® files. Paper points were used to collect microbiological samples before (1A samples) and after (1B samples) irrigation. Viable colony-forming units (CFU) were quantified twice: (1) without speciation, and (2) only for Enterococcus Faecalis(EF). Statistical analysis was performed using SPSS 22.0 for Windows. RESULTS: No significant differences were observed between NaOCl and CHX in the reduction of CFU; in fact, reduction was < 93% for the two irrigants. Conversely, statistically significant differences were found between the two activation techniques (sonic and ultrasonic) in the reduction of Enterococcus Faecalis(EF). Thus, the effectiveness of ultrasonic activation was significantly higher (< 93%; p=0.012) as compared to sonic activation. Following the combination of the two irrigants with the two activation techniques (groups A, B, C and D), significant differences were observed between group A and B (p=0.025) in the reduction of EF populations, reaching up to 94%. CONCLUSIONS: NaClO and CHX are effective in reducing intracanal bacterial load. Ultrasonic activation is the most effective activation technique in reducing EF populations. KEY WORDS: Chlorhexidine gluconate, sodium hypochlorite, ultrasonic irrigation, sonic irrigation, apical periodontitis, Enterococcus faecalis.

Diagnosis and endodontic treatment of type II dens invaginatus by using cone-beam computed tomography and splint guides for cavity access: a case report.

BACKGROUND AND OVERVIEW: Dens invaginatus (DI) is defined as a rare dental malformation. The inherent structural variants of this anatomic disorder make it difficult to perform conventional endodontic treatment procedures by means of a conservative access cavity. In this clinical case report, the authors describe the treatment of a type II DI by means of guided splints for cavity access. CASE DESCRIPTION: This is a clinical report of a case of type II DI in a maxillary lateral incisor. The authors established the diagnosis by means of cone-beam computed tomography (CBCT). The authors manufactured 3 splint guides from a Digital Imaging and Communications in Medicine file and a stereolithography file obtained from a plaster model of the patient by using software for guided implant placement, for access opening, and for locating the root canals. CONCLUSIONS: CBCT is an effective method for obtaining information about the root canal system in teeth with DI. In addition, guided implant surgery software is effective for manufacturing splint guides for endodontic treatment with conservative pulp chamber access. PRACTICAL IMPLICATIONS: Information obtained from CBCT allows the clinician to fabricate splint guides for minimally invasive access opening in this type of case, thus reducing the loss of dental tissue.

Lactobacillus rhamnosus as additive for maize and sorghum ensiling.

The effects of Lactobacillus rhamnosus AT195, a potential probiotic microorganism cultured in buffalo "scotta" whey, on chemical and microbiological composition in maize and sorghum ensiling were evaluated. Both crops were harvested, chopped, and treated or not with the selected strain prior to ensiling in fiberglass vertical silos; 90 days after ensiling, silages were sensorially evaluated and sampled. Different chemical components were evaluated both on fresh crops and silages: in particular, the water-soluble carbohydrates content was investigated by high-field NMR spectroscopy and the carbohydrate fermentation profile was performed by GC. Besides phenotypic identification and typing, microbiological studies included Lb. rhamnosus genotype typing by RAPD-PCR. All silages, inoculated or not, were well preserved, as their chemical and microbiological data along with the fermentation profiles showed. The selected strain used as inoculum influenced the lactic acid population of silages and evidenced a good survival performance during the ensiling process of both maize and sorghum. Moreover, the use of Lb. rhamnosus strain efficiently improved the quality of the multifactorial ensiling process by significantly reducing the ammonia nitrogen content of both maize and sorghum silages.

Evaluation of three antimicrobial regimens used as metaphylaxis in stocker calves at high risk of developing bovine respiratory disease.

A total of 894 calves at high risk for bovine respiratory disease were processed at two sites and randomly assigned to receive one of three antimicrobial metaphylactic regimens to determine if a two-drug regimen offered any advantage over the more conventional one-course regimens. On arrival, calves received either a two-course regimen of ceftiofur crystalline free acid (CCFA) followed by tulathromycin 8 days later (Group 1) or a one-course regiment of CCFA (Group 2) or tilmicosin (Group 3). At Site A, morbidity was significantly lower (52%) in Group 1 than in Group 2 (76.3%) and Group 3 (78.4%). At Site B, morbidity was significantly lower in Group 1 (2.6%) than in Group 2 (9.4%) and Group 3 (7.2%).