Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA.

BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.

Does third molar agenesis influence the second lower molar mineralization?

Different studies have established that the mineralization stages of the second mandibular molar can be used in forensic age estimation. Nowadays, the estimate's accuracy is an ethical concern, producing as few false positives (individuals incorrectly classified as older than a determined threshold) and false negatives (individuals incorrectly classified as younger than a determined threshold) as possible. Some have hypothesized that changes in teeth number may influence tooth mineralization, altering the age estimate process. This paper analyzes whether third molar agenesis affects the second mandibular molar mineralization time frame. To do so, 355 orthopantomograms were evaluated for third molar agenesis, and the second mandibular molar mineralization stage was assessed using the Demirjian stages. Student's t-test was used to compare the difference in the mean age at which the various stages of 37 mineralization were reached in the groups with and without third molar agenesis. The level of statistical significance was set at 5%. The results pointed to a delay in second mandibular molar mineralization in the case of agenesis, suggesting the need to consider this when estimating age using dental techniques.

Portuguese version of Parent-reported Drug Hypersensitivity Quality of Life Questionnaire (P-DrHy-Q): assessment of reliability and validity.

Summary: Background. Drug hypersensitivity in children impacts the quality of life of the patients and their caregivers. The parent-reported drug hypersensitivity quality of life questionnaire (P-DrHy-Q), the first disease-specific quality-of-life questionnaire for caregivers who have children with drug hypersensitivity, was recently developed. The aim of this study was to assess the validity and reliability of the portuguese version of the P-DrHy-Q. Methods. A translation of the Parent-reported Drug Hypersensitivity Quality of Life Questionnaire (P-DrHy-Q) to the Portuguese population was performed, assessing its applicability in 74 caregivers from two allergy departments. The analyses included internal consistency (Cronbach's alpha) and test-retest reliability: 14 caregivers completed the P-DrHy-Q without any intervention one week after answering the first questionnaire. Results. The 12-item scale assessed the mental health and social activity. The internal consistency of the scale was good (Cronbach's alpha = 0.884) and the test-retest associations were excelent (intra-class correlation coefficient = 0.985; p < 0.001). The mean value of the questionnaire was 37.01 (SD 18.57) with Mental Health being more affected than Social Activity. Employed caregivers had a significant higher score (p < 0.001). No other factor was statistically significant. Conclusions. The Portuguese version of the P-DrHy-Q is valid for evaluating quality of life impairment in Portuguese caregivers of children with drug hypersensitivity. Its application might be relevant for future research and provide clinicians and researchers with a tool to define which psychosocial support is required to provide more comprehensive care in drug hypersensitivity.

Early decrease in lean mass and bone mass in postmenopausal women: a cross-sectional study.

OBJECTIVE: The effect of menopause transition in body composition was evaluated in a cross-sectional study. METHOD: The study was carried out in an outpatient clinic of Brazil enrolling premenopausal (n = 64) and postmenopausal (n = 42) women aged between 44 and 52 years, with weight stability (±2 kg) for at least 6 months before evaluation. Participants answered a sociodemographic semi-structured questionnaire, the Menopause Rating Scale, the International Physical Activity Questionnaire, 24-h dietary recall and a visual analogue scale of appetite. Blood biochemical, anthropometry and densitometry measurements were used for body composition estimation. RESULTS: Most participants were overweight (31.4%) or obese (45.7%) and categorized as 'high active' in physical activity (65.7%). Lean mass and bone mass decreased in the first few years of menopause. A metabolic turn to an increase of lipids was observed, represented by greater total cholesterol and high-density lipoprotein cholesterol levels. Menopause transition did not alter body fat distribution. Total body fat, android fat and gynoid fat were positively related to smoking habit, and android fat was also positively related to waist circumference. CONCLUSION: Taken together, early postmenopause can be considered a time window of opportunity for preventing ailments such as atherogenic profile, obesity, increased cardiovascular risk and osteoporosis.

Polycystic ovary syndrome: clinical and laboratory variables related to new phenotypes using machine-learning models.

PURPOSE: Polycystic Ovary Syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. Machine learning (ML) is the area of artificial intelligence with a focus on predictive computing algorithms. We aimed to define the most relevant clinical and laboratory variables related to PCOS diagnosis, and to stratify patients into different phenotypic groups (clusters) using ML algorithms. METHODS: Variables from a database comparing 72 patients with PCOS and 73 healthy women were included. The BorutaShap method, followed by the Random Forest algorithm, was applied to prediction and clustering of PCOS. RESULTS: Among the 58 variables investigated, the algorithm selected in decreasing order of importance: lipid accumulation product (LAP); abdominal circumference; thrombin activatable fibrinolysis inhibitor (TAFI) levels; body mass index (BMI); C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-c), follicle-stimulating hormone (FSH) and insulin levels; HOMA-IR value; age; prolactin, 17-OH progesterone and triglycerides levels; and family history of diabetes mellitus in first-degree relative as the variables associated to PCOS diagnosis. The combined use of these variables by the algorithm showed an accuracy of 86% and area under the ROC curve of 97%. Next, PCOS patients were gathered into two clusters in the first, the patients had higher BMI, abdominal circumference, LAP and HOMA-IR index, as well as CRP and insulin levels compared to the other cluster. CONCLUSION: The developed algorithm could be applied to select more important clinical and biochemical variables related to PCOS and to classify into phenotypically different clusters. These results could guide more personalized and effective approaches to the treatment of PCOS.

Relationship of cow and calf circulating lipidomes with colostrum lipid composition and metabolic status of the cow.

Newborn calves rely on lipids in colostrum for energy and immune function. The lipid concentration in colostrum, however, is highly variable, and little is known about its composition and maternal factors that influence its composition. The first objective was to measure plasma lipid composition of multiparous cows at 35 d before calving (BC; 35 ± 3 d; ± standard deviation) and 7 d BC (7 ± 2 d), their colostrum, and serum lipid composition of calves (24 h after birth) using multiple reaction monitoring profiling, which is an exploratory and highly sensitive lipidomic analysis method that screens lipids based on chemical functionality. Second, data were analyzed to determine if there were relationships between circulating lipids in the cow, colostrum lipids, and calf serum lipids. Third, relationships between markers of metabolic status of the cows and circulating and colostrum lipids were analyzed with correlation analysis. Blood was sampled and plasma prepared from multiparous cows (n = 16) at 35 and 7 d BC. Within 3 h of parturition, colostrum was collected from cows and fed to her calf. Calves received another feeding of colostrum within 12 h after birth and a serum sample was collected from each calf 24 h after the first feeding of colostrum. The metabolic status of cows was evaluated using insulin, glucose, and nonesterified fatty acid area under the curve in response to an intravenous glucose tolerance test performed at 3 wk BC. Lipids were extracted from plasma, colostrum, and calf serum and were analyzed using multiple reaction monitoring profiling. Concentration of lipids were calculated using spiked in standards and expressed as percent of lipids identified. Data were uploaded into MetaboAnalyst 5.0 for multivariate and univariate analysis. Principal component analysis indicated that circulating lipids in the cow and calf were distinct from lipids in colostrum. Phosphatidylglycerol (PG) concentration was greater in colostrum and calf serum than in cow plasma, with 23 of the 24 PG found in colostrum also found in calf serum. In response to intravenous glucose tolerance test in late gestation, nonesterified fatty acid area under the curve was positively related to total triacylglycerols lipids in 7 d BC plasma (r = 0.63) but negatively related to total membrane lipids in colostrum (r = -0.55). Thus, the metabolic status of the dam influences circulating lipids and colostrum lipid content. Moreover, the circulating lipidome of the cow and calf are similar to one another and distinct from the colostrum lipidome, except for PG, where it appears that colostrum serves as the source for PG in the calf's circulation.

Protective effects of antioxidants on striatal dopamine release induced by organophosphorus pesticides.

Although the toxic effects of organophosphorus (OP) pesticides have been classically attributed to inhibition of the acetylcholinesterase, other neurotoxic mechanisms, as oxidative stress can also occur. Here we evaluated if antioxidants prevent the excessive dopamine release induced by OP pesticides in conscious and freely moving rats, using cerebral microdialysis technique. Intrastriatal infusion of paraoxon (5 mM), glufosinate (10 mM) or glyphosate (5 mM) significantly increased the dopamine release (1006 ± 106%, 991 ± 142%, and 1164 ± 128%, relative to baseline, respectively). To evaluate if these increased dopamine release could be related to oxidative stress, we pretreated animals with antioxidants glutathione (GSH, 400 or 800 µM), dithiothreitol (DTT, 5 or 10 µM), trolox (1 or 3 mM), and α-lipoic acid (ALA, 400 or 800 µM) before administration of OP pesticides. Intrastriatal administration of the antioxidants GSH, DTT, trolox, and ALA was highly effective in preventing the glyphosate and glufosinate-induced dopamine overflow. However, only GSH (800 µM) significantly decreased the effect of paraoxon on dopamine levels. The high toxicity of this pesticide and the low concentrations used could explain this lack of effect in our experimental conditions. The fact that ROS scavengers prevent the excessive dopamine release induced by OP pesticides, further supports the view that dopamine overflow can cause neuronal damage mediated, at least in part, by oxidative stress.

Body image shame in men: confirmatory factor analysis and psychometric properties of the Body Image Shame Scale.

PURPOSE: Body image shame plays a key role in disordered eating symptoms and psychological adjustment. Nonetheless, research has been mainly focussed on women. The Body Image Shame Scale (BISS) was previously developed and tested in a nonclinical sample of women. This study examines the BISS in a sample of men comprising students and community participants. METHODS: Participants were 420 men, who completed the BISS and self-report measures of shame, self-criticism, body weight and shape concerns, and psychopathological symptoms. RESULTS: The previously identified structure of the BISS, with an external and internal dimension, fitted the data well. All items presented high reliability. The BISS total score and its subscales in men present high construct reliability, and convergent and discriminant validity. Correlation analyses indicated that BISS and its subscales in men present positive associations with general shame and self-criticism, body weight and shape concerns, and with indices of poorer psychological adjustment. CONCLUSION: Findings supported that the BISS is a reliable measure to assess body shame in men. LEVEL OF EVIDENCE: III: Evidence obtained from well-designed cohort or case-control analytic studies.

Assessing the effects of PMM2 variants on protein stability.

Phosphomannomutase 2 deficiency, PMM2-CDG, is the most frequent disorder of protein N-glycosylation. It is an autosomal recessive disease with a broad clinical and biochemical phenotype. Trying to predict the impact of novel variants is often a challenge due to the high number of variants and the difficulty to establish solid genotype-phenotype correlations. A potential useful strategy is to use computational chemistry calculations as a tool from which relevant information on the structural impact of novel variants may be deduced. Here we present our analyses based on four well-known PMM2 deleterious variants (p.(Leu32Arg), p.(Asp65Tyr), p.(Phe119Leu), p.(Arg141His)) and the polymorphic p.(Glu197Ala) for which we have predicted the effect on protein stability. Our work predicts the effect of different amino acid residues on the conformation and stability of PMM2. These computational simulations are, therefore, an extremely useful methodology which, in combination with routinely used in silico methods of pathogenicity prediction, may help to reveal the structural impact of novel variants at the protein level, potentially leading to a better understanding of target biological molecules.

Influence of variations in the environmental pH on the solubility and water sorption of a calcium silicate-based root canal sealer.

AIM: To evaluate the influence of pH variation on the solubility and water sorption of a premixed calcium silicate-based root canal sealer (EndoSequence BC Sealer) compared to the gold standard based on epoxy resin (AH Plus Jet) after immersion in distilled water and phosphate-buffered saline (PBS). METHODOLOGY: Solubility and water sorption were evaluated after immersion in distilled water or PBS at several pHs (5, 7 and 12) and the values were calculated as percentages of the original mass after 24 h, 7 and 30 days of immersion. The crystalline structures present in the sealers and surface precipitates were assessed by X-ray diffraction. The Shapiro-Wilk's test revealed that data were normally distributed; thus, statistical analysis was performed using one-way anova and Tukey's tests or independent t-test, assuming a 5% α-error. RESULTS: EndoSequence BC Sealer was associated with significantly greater water sorption and solubility compared to AH Plus Jet in all tested conditions (P < 0.05). The acid environment increased the 24 h solubility of EndoSequence BC Sealer immersed in PBS (P < 0.05) and did not induce significative changes in the water sorption (P > 0.05). Alkaline pH reduced the solubility of EndoSequence BC Sealer and increased that of AH Plus Jet at all experimental times and soaking media (P < 0.05). Alkaline environment also significantly increased the water sorption of AH Plus Jet immersed in PBS (P < 0.05). Immersion in PBS significantly reduced the solubility of EndoSequence BC Sealer and significantly increased that of AH Plus Jet (P < 0.05). Precipitates on the surface of EndoSequence BC Sealer corresponding to hydroxyapatite and calcium carbonate were detected after immersion in PBS at pH 5 and 7 for 30 days. CONCLUSIONS: EndoSequence BC Sealer had significantly greater solubility and water sorption than AH Plus Jet. Although the alkaline pH and soaking media directly influenced the solubility and water sorption of the sealers, the solubility of AH Plus Jet remained within the limits recommended by ISO 6876, whilst the solubility of the EndoSequence BC Sealer did not comply with ISO recommendations in all the conditions tested.

Influence of ultraconservative access cavities on instrumentation efficacy with XP-endo Shaper and Reciproc, filling ability and load capacity of mandibular molars subjected to thermomechanical cycling.

AIM: To evaluate the influence of ultraconservative access cavities (UltraAC) on canal shaping and filling ability and load capacity of mandibular molars after root canal preparation with XP-endo Shaper (XP) or Reciproc (RC), under simulated clinical conditions. Traditional access cavities (TradAC) were used for comparison. METHODOLOGY: Forty extracted mandibular molars were scanned by micro-computed tomographic and, based on similar anatomical features, were divided into four groups (n = 10), according to the type of access cavity and canal instrumentation protocol: TradAC/RC, TradAC/XP, UltraAC/RC and UltraAC/XP. All root canal procedures were performed with the teeth placed in a dental mannequin. Teeth were scanned after root canal instrumentation and filling. Unprepared canal area, dentine removed, accumulated hard tissue debris (AHTD), canal transportation, presence of voids and filling material remnants within the pulp chamber were analysed. After restorative procedures, the teeth were subjected to thermomechanical cycling and to a load capacity test. Statistical analyses were performed using two-way anova test, considering the randomized blocks design (P < 0.05). RESULTS: The percentage of unprepared canal area was significantly lower in TradAC groups when compared to UltraAC groups (P < 0.05), regardless of the instrument used. The UltraAC/XP group had significantly lower percentage of root dentine removed when compared to other groups (P < 0.05). UltraAC/XP and TradAC/XP groups had significantly lower percentages of AHTD than UltraAC/RC and TradAC/RC groups (P < 0.05). Regarding canal transportation, in the MB root canals, the TradAC/XP group had significantly lower values than other groups (P < 0.05). In general, in ML and distal root canals, TradAC/XP and UltraAC/XP groups had significantly lower values of canal transportation when compared to other groups (P < 0.05). Moreover, the UltraAC/RC had the greatest canal transportation values in MB and distal canals. The UltraAC groups had significantly greater percentages of voids and volume of remaining root filling material within the pulp chamber after cleaning procedures than TradAC groups (P < 0.05). There was no difference in the load capacity amongst groups (P < 0.05). CONCLUSION: The UltraAC/XP and UltraAC/RC groups had significantly greater areas of unprepared canal walls, significantly more voids and volume of root filling material remnants within the pulp chamber after canal filling. UltraAC/XP was associated with significantly less root dentine removal and significantly more AHTD whilst TradAC/XP had overall significantly less canal transportation. No differences were observed in the load capacity amongst groups.

Emerging new avian reovirus variants from cases of enteric disorders and arthritis/tenosynovitis in Brazilian poultry flocks.

1. The objective of this study was to characterise circulating Brazilian avian reovirus (ARV) strains by genetic analysis of the σC protein encoded by segment 1 of the viral genome and compare these with those of viral strains used for immunising commercial poultry.2. The analysis detected the presence of ARV genomes by quantitative reverse transcriptase PCR (RT-qPCR) in the enteric samples and the joint tissues (JT) of birds with signs of viral arthritis/tenosynovitis. Nucleotide sequencing used 16 strains (three commercial vaccines, 10 from enteric tissues and three from JT). The results indicated high variability in the amino acid sequences of 13 wild strains, showing between 40% and 75% similarity compared with the vaccine strains (S1133 and 2177).3. The sequences were grouped into three well-defined clusters in a phylogenetic tree, two of these clusters together with previous Brazilian σC ARV sequences, and one cluster (VII) that was novel for Brazilian strains. Antigenic analysis showed that there were amino acids within putative epitopes located on the surface of the receptor-binding region of the σC protein with a high degree of variability.4. The study confirmed the presence of ARV genetic variants circulating in commercial birds in Brazil, and according to the antigenic prediction, the possibility of antigenic variants appears to be high.

Taking the inner route: spatial and demographic factors affecting vulnerability to COVID-19 among 604 cities from inner São Paulo State, Brazil.

Even though the impact of COVID-19 in metropolitan areas has been extensively studied, the geographic spread to smaller cities is also of great concern. We conducted an ecological study aimed at identifying predictors of early introduction, incidence rates of COVID-19 and mortality (up to 8 May 2020) among 604 municipalities in inner São Paulo State, Brazil. Socio-demographic indexes, road distance to the state capital and a classification of regional relevance were included in predictive models for time to COVID-19 introduction (Cox regression), incidence and mortality rates (zero-inflated binomial negative regression). In multivariable analyses, greater demographic density and higher classification of regional relevance were associated with both early introduction and increased rates of COVID-19 incidence and mortality. Other predictive factors varied, but distance from the State Capital (São Paulo City) was negatively associated with time-to-introduction and with incidence rates of COVID-19. Our results reinforce the hypothesis of two patterns of geographical spread of SARS-Cov-2 infection: one that is spatial (from the metropolitan area into the inner state) and another which is hierarchical (from urban centres of regional relevance to smaller and less connected municipalities). Those findings may apply to other settings, especially in developing and highly heterogeneous countries, and point to a potential benefit from strengthening non-pharmaceutical control strategies in areas of greater risk.

Adherence to treatment in children with growth hormone deficiency, small for gestational age and Turner syndrome in Mexico: results of the Easypod™ connect observational study (ECOS).

BACKGROUND: Assessing adherence to growth hormone (GH) is challenging. The Easypod™ connect device delivers pre-set doses of recombinant human GH (r-hGH) and stores a digital record of adherence that can be shared with healthcare provider. We assessed adherence to r-hGH delivered with Easypod™ according to the approved pediatric indications for r-hGH: growth hormone deficiency (GHD), born small for gestational age (SGA) who failed to show catch-up growth and Turner syndrome (TS). METHODS: ECOS (NCT01555528) was a multicenter (24 countries), 5-year, longitudinal, observational study, which aimed to evaluate country-specific adherence to r-hGH therapy prescribed via the Easypod™ electronic injection device. The primary endpoint was yearly adherence. Secondary endpoints were height velocity, height velocity standard deviation scores (SDS), height, height SDS and IGF-1 concentrations. Clinical and auxological data were obtained from medical records and adherence from Easypod™ logs. RESULTS: This study included 147 Easypod™-naïve Mexican children assessed during 3 years (mean age: 9.96 ± 3.41 years, 56.8% boys, mean height SDS at baseline: - 2.17 ± 0.97): 118 with GHD, 24 SGA and 5 with TS. A total of 105 (71.4%) patients were GH naïve. Overall median adherence was > 90% over the first year of treatment and > 80% at 3 years. Adherence was not different by r-hGH indication or between GH-naïve or experienced patients. At 1-year follow-up, mean change in height SDS was 0.57 ± 0.34, whereas mean height velocity SDS was 2.85 ± 2.51. In all, 84.7% patients had normal IGF-1 concentrations at 1-year follow-up. Adherence was associated with change in height SDS (r = 0.239, p = 0.005) and height velocity SDS (r = 0.194, p = 0.027). CONCLUSION: Adherence rates with the Easypod™ device are high and maintained over time in GHD, SGA and TS Easypod™-naïve Mexican patients. High adherence is associated with better outcomes. Easypod™ assists physicians in monitoring adherence to r-hGH.

Does tobacco smoking predispose to apical periodontitis and endodontic treatment need? A systematic review and meta-analysis.

BACKGROUND: Controversial findings exist in the literature regarding the association between tobacco smoking and development of apical periodontitis or need for root canal treatment, with some studies reporting an increase in the prevalence of these outcomes in smokers, whilst others reporting no association. AIM: To evaluate if there is scientific evidence to support an association between tobacco smoking and a greater prevalence of apical periodontitis and/or root canal treatments. DATA SOURCES: A systematic search was performed using MeSH terms and free terms in the PubMed, Scopus, Virtual Health Library (VHL), Cochrane library and Open Gray databases. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Observational studies that evaluated the association between smoking and the development or healing of periapical lesion and/or the prevalence of root canal treatment in humans were included. STUDY APPRAISAL AND SYNTHESIS METHODS: A quality assessment of included studies was performed, and the relevant information and findings were evaluated. A meta-analysis using nine included studies was performed through RevMan software, and the certainty of evidence was evaluated through GRADE. RESULTS: Fifteen studies were included, of which 10 were classified as low risk of bias, 4 were considered as moderate risk of bias and 1 as high risk of bias. Ten studies reported that smoking was associated with a greater prevalence of periapical periodontitis and/or root canal treatment. Five studies reported no association. Nine studies were included in the pooled meta-analysis, comprising two subgroups: apical periodontitis and root canal treatment. From these nine studies, eight studies were included in the apical periodontitis subgroup meta-analysis and demonstrated that this condition was significantly more prevalent in smokers when compared to the nonsmokers (odds ratio = 2.78[CI: 1.60, 4.85], P < 0.001; I2  = 79%; no adjusted odds ratio). Three studies were included in the root canal treatment subgroup meta-analysis and demonstrated an increased prevalence in smokers when compared to the nonsmokers (odds ratio = 2.73 [CI: 1.06, 2.83], P < 0.001; I2  = 72%; no adjusted odds ratio). The pooled meta-analysis demonstrated that smokers had twice the chance of having apical periodontitis and/or root canal treatment when compared to nonsmokers (odds ratio of 2.42 [CI: 1.59, 3.68], P < 0.01; I2  = 85%). The GRADE analysis demonstrated moderate certainty of evidence. LIMITATIONS: Several confounding factors were identified such as misinformation regarding the period of time subjects had smoked, as well as the frequency of smoking and the number of cigarettes consumed. No adjustment in odds ratio data for confounding was performed. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: This systematic review and meta-analysis indicate that tobacco smokers have an increased prevalence of periapical periodontitis and root canal treatments with moderate certainty of evidence.

Current status on minimal access cavity preparations: a critical analysis and a proposal for a universal nomenclature.

In the last decade, several access cavity designs involveing minimal removal of tooth tissue have been described for gaining entry to pulp chambers during root canal treatment. The premise behind this concept assumes that maximum preservation of as much of the pulp chamber roof as possible during access preparation would maintain the fracture resistance of teeth following root canal treatment. However, the smaller the access cavity, the more difficult it may be to visualize and debride the pulp chamber as well as locate, shape, clean and fill the canals. At the same time, a small access cavity may increase the risk of iatrogenic complications as a result of poor visibility, which may have an impact on treatment outcome. This study aimed to critically analyse the literature on minimal access cavity preparations, propose new nomenclature based on self-explanatory abbreviations and highlight the areas in which more research is required. The search was conducted without restrictions using specifics terms and descriptors in four databases. A complementary screening of the references within the selected studies, as well as a manual search in the highest impact journals in endodontics, namely International Endodontic Journal and Journal of Endodontics, was also performed. The initial search retrieved 1831 publications. The titles and abstracts of these papers were reviewed, and the full text of 94 studies was assessed. Finally, a total of 28 studies were identified as evaluating the influence of minimally invasive access cavity designs on the fracture resistance of teeth and on the different stages of root canal treatment (orifice location, canal shaping, canal cleaning, canal filling and retreatment). Overall, the studies had major methodological drawbacks and reported inadequate and/or inconclusive results on the utility of minimally invasive access preparations. Furthermore, they offered limited scientific evidence to support the use of minimally invasive access cavities to improve the outcome of root canal treatment and retreatment; they also provided little evidence that they preserved the fracture resistance of root filled teeth to a greater extent than traditional access cavity preparations. It was concluded that at present, there is a lack of supporting evidence for the introduction of minimally invasive access cavity preparation into routine clinical practice and/or training of undergraduate and postgraduate students.

The influence of endodontic access cavity design on the efficacy of canal instrumentation, microbial reduction, root canal filling and fracture resistance in mandibular molars.

AIM: To assess the impact of conservative endodontic access cavities (CEC) and truss access cavities (TAC) during root canal treatment performed on mandibular molars in terms of: ability to shape and fill root canals, microbial reduction in canals, and cleaning of the pulp chamber. In addition, the fracture resistance of the teeth after coronal restoration was assessed. Traditional endodontic cavities (TEC) were used as a reference technique for comparison. METHODOLOGY: Thirty extracted intact mandibular molars were scanned in a microcomputed tomography device (micro-CT), matched based on similar anatomical features and assigned to TEC, CEC or TAC groups (n = 10). The specimens were accessed accordingly, and root canals were contaminated with bacterial suspensions of Enterococcus faecalis (21 days). Subsequently, the first microbial sample was collected from root canals (S1). The canals were initially prepared with Reciproc Blue R25 instrument followed by a second instrumentation using Reciproc Blue R40. Eight mL of 0.5% NaOCl were used as an irrigant for each instrument. A final irrigation protocol was performed with 2 mL of 0.5% NaOCl, 2 mL of 17% EDTA and another 2 mL of 0.5% NaOCl. Microbial samples were collected from root canals after R25 (S2), R40 (S3) and final irrigation (S4). The teeth were rescanned after S4. Then, root canals were filled, rescanned, restored and the teeth subjected to fracture resistance tests. The statistical analysis was performed with type I negative binomial and beta 0-1 inflation regression models for microbiological analysis. Instrumentation, filling and resistance to fracture results were subjected to anova and Tukey tests (P < 0.05). RESULTS: S4 revealed no significant variations in microbial reduction amongst the groups (P > 0.05). TEC had a significantly lower percentage of unprepared surface area than CEC (P < 0.05). No differences were found regarding the percentage of dentine removed, transportation, centring ability and filling voids amongst the groups (P > 0.05). The TEC group had a significantly lower volume of remaining root filling material within the pulp chamber than CEC and TAC groups (P < 0.05). There was no difference regarding fracture resistance amongst the groups (P > 0.05). CONCLUSION: Conservative access cavities did not offer any advantage in comparison with the traditional endodontic cavities in any of the parameters considered. Furthermore, conservative methods were associated with larger percentages of unprepared canal surface area and larger volumes of remaining root filling material within the pulp chamber.

The impact of minimally invasive root canal preparation strategies on the ability to shape root canals of mandibular molars.

AIM: To evaluate the use of a reduced taper endodontic instrument system (Bassi Logic™ .03 taper) and expandable heat-treated system (XP-endo Shaper) on the ability to shape canals in mandibular molars, by means of microcomputed tomography (micro-CT) analysis. The Reciproc system was used as the reference for comparison. METHODOLOGY: Twenty-four mandibular molars were scanned in a micro-CT, matched based on similar anatomical features and sorted into three groups (n = 8 per group), according to root canal preparation system: Bassi Logic™ .03, XP-endo Shaper and Reciproc. The teeth were mounted onto a mannequin and the pulp chambers were accessed with traditional access cavities. In Bassi Logic™ .03 and Reciproc groups, mesial canals were prepared with size 25, .03 taper or R25 (size 25, .08v taper) instruments and the distal root canal with size 25, .03 taper and size 40, .03 taper or R25 and R40 (size 40, .06v taper), respectively. In XP-endo Shaper groups, all root canals were prepared with XP-endo Shaper (size 30, .04v taper). After root canal preparation, the teeth were rescanned. The percentage of untouched canal areas and the percentage of removed dentine were evaluated separately for mesial and distal root canals. The data were analysed using one-way anova and Tukey tests (P < 0.05). RESULTS: The Bassi Logic™ .03 group was associated with a greater percentage of untouched canal areas when compared to XP-endo Shaper and Reciproc groups for mesial and distal root canals (P < 0.05), but no differences were found between XP-endo Shaper and Reciproc groups (P > 0.05). No significant difference was observed in the percentage of dentine removed amongst the groups for mesial and distal root canals (P > 0.05). CONCLUSION: The use of a reduced taper system (Bassi Logic™ .03) during root canal preparation resulted in a greater percentage of untouched canal areas when compared to XP-endo Shaper and Reciproc instruments. No differences were observed amongst the systems regarding the percentage of dentine removed.

A laboratory study of the impact of ultraconservative access cavities and minimal root canal tapers on the ability to shape canals in extracted mandibular molars and their fracture resistance.

AIM: To evaluate the influence of ultraconservative endodontic access cavities (UEC) and the use of instruments with various tapers (.03 or .05) and tip diameters (25 or 40) on the ability to shape canals in mandibular molars and their fracture resistance in comparison with traditional endodontic access cavities (TEC). METHODOLOGY: Thirty-two intact extracted mandibular molars were scanned in a micro-computed tomography device, matched based on similar anatomical features and assigned to UEC or TEC groups and to subgroups according to mechanical canal preparation with Bassi Logic™ rotary NiTi instruments with .03 or .05 taper (n = 8 per group). The teeth were mounted onto a mannequin head, and the pulp chambers were accessed and the root canals subjected to instrumentation. In the first stage, size 25 endodontic instruments were used, with .03 or .05 tapers. The teeth were re-scanned. Subsequently, a second canal instrumentation was performed with the size 40 instruments with .03 or .05 tapers and scanned again. The root canals were filled and then the teeth restored before being subjected to fracture resistance tests. The data on untouched canal areas, canal transportation, centring ability, the percentage of removed dentine and maximum load at fracture were analysed. One-way anova and Tukey's tests were performed for inter-group analysis. The paired-samples t-test was performed on the results between size 25 and size 40 apical preparations for each individual specimen (P < 0.05). RESULTS: No significant difference was observed for the percentage of untouched canal area when comparing UEC and TEC groups or between the .03 and .05 tapers with the same instrument tip size (P > 0.05). There was a significantly lower percentage of untouched canal area after instrumentation with size 40 instruments when compared to size 25 (P < 0.05). No significant difference in the percentage of dentine removed was observed between the access cavities or the different tapers (P > 0.05). Size 40 apical preparations removed significantly more dentine than size 25 preparations (P < 0.05). No significant differences were observed in canal transportation, centring ability and fracture resistance in any of the tested groups (P > 0.05). CONCLUSIONS: Ultraconservative endodontic access cavities did not offer any advantages in comparison with traditional endodontic access cavities on the ability to shape canals, nor the fracture resistance of mandibular molars. No differences were observed in shaping ability and fracture resistance between .03 and .05 taper canal preparations. Apical preparation with larger instruments resulted in significantly less untouched canal area in all groups.

Effects of alcohol and nicotine consumption on the development of apical periodontitis in rats: a correlative micro-computed tomographic, histological and immunohistochemical study.

AIM: To evaluate the effects of alcohol and nicotine, when used alone or simultaneously, in the development of apical periodontitis induced in rats, using a correlative analytic approach with micro-CT, histological and immunohistochemical analysis. METHODOLOGY: Twenty-eight male Wistar rats were arranged into four groups: Control, Nicotine, Alcohol and Alcohol + Nicotine. The alcohol groups were exposed to self-administration of a 25% alcohol solution, whilst the other groups drunk only filtered water. The nicotine groups received daily intraperitoneal injections of a solution with 0.19 µL of nicotine per mL, whilst the other groups received saline solution. The pulps of the left mandibular first molars were exposed for 28 days to induce periapical lesions. Throughout the experiment, drug administration was maintained, and the animals had their weight and solid and liquid consumption measured. After euthanasia, the mandibles were removed and the area, volume and major diameter of the periapical lesions were measured using micro-computed tomography images. The samples were submitted to histopathological evaluation and immunohistochemistry for RANKL and PTHrP. Statistical analysis was undertaken with a significance level of 5%. Nonparametric data were analysed using the Kruskal-Wallis test followed by Dunn's test, whilst one-way anova followed by Tukey's test was performed for parametric data. RESULTS: The alcohol groups had lower solid and liquid consumption and gained less weight when compared to the nonalcohol groups (P < 0.05). The Alcohol + Nicotine group had lesions with significantly larger volume and area when compared to the other groups (P < 0.05), whilst the Alcohol or Nicotine groups had significantly larger lesions than the control group (P < 0.05). There was no significant difference in the largest diameter of the lesions amongst groups (P > 0.05). The experimental groups had greater inflammatory response scores than the control group (P < 0.05), and the representative samples had more pronounced immunoreaction against RANKL and PTHrP antibodies. CONCLUSIONS: Alcohol and nicotine consumption exacerbated the inflammatory response and the development of periradicular lesions in rats. The association of both substances enhanced their harmful effects.