First-line therapy with palbociclib in patients with advanced HR+/HER2- breast cancer: The real-life study PALBOSPAIN.

PURPOSE: To evaluate the efficacy and safety of first-line therapy with palbociclib in a Spanish cohort treated after palbociclib approval. METHODS: PALBOSPAIN is an observational, retrospective, multicenter study evaluating real-world patterns and outcomes with 1 L palbociclib in men and women (any menopausal status) with advanced HR+/HER2- BC diagnosed between November 2017 and November 2019. The primary endpoint was real-world progression-free survival (rw-PFS). Secondary endpoints included overall survival (OS), the real-world response rate (rw-RR), the clinical benefit rate, palbociclib dose reduction, and safety. RESULTS: A total of 762 patients were included. The median rw-PFS and OS were 24 months (95% CI 21-27) and 42 months (40-not estimable [NE]) in the whole population, respectively. By cohort, the median rw-PFS and OS were as follows: 28 (95% CI 23-39) and 44 (95% CI 38-NE) months in patients with de novo metastatic disease, 13 (95% CI 11-17) and 36 months (95% CI 31-41) in patients who experienced relapse < 12 months after the end of ET, and 31 months (95% CI 26-37) and not reached (NR) in patients who experienced relapse > 12 months after the end of ET. rw-PFS and OS were longer in patients with oligometastasis and only one metastatic site and those with non-visceral disease. The most frequent hematologic toxicity was neutropenia (72%; grade ≥ 3: 52.5%), and the most common non-hematologic adverse event was asthenia (38%). CONCLUSION: These findings, consistent with those from clinical trials, support use of palbociclib plus ET as 1 L for advanced BC in the real-world setting, including pre-menopausal women and men. TRIAL REGISTRATION NUMBER: NCT04874025 (PALBOSPAIN). Date of registration: 04/30/2021 retrospectively registered.

Analysis and applications of respiratory surface EMG: report of a round table meeting.

Surface electromyography (sEMG) can be used to measure the electrical activity of the respiratory muscles. The possible applications of sEMG span from patients suffering from acute respiratory failure to patients receiving chronic home mechanical ventilation, to evaluate muscle function, titrate ventilatory support and guide treatment. However, sEMG is mainly used as a monitoring tool for research and its use in clinical practice is still limited-in part due to a lack of standardization and transparent reporting. During this round table meeting, recommendations on data acquisition, processing, interpretation, and potential clinical applications of respiratory sEMG were discussed. This paper informs the clinical researcher interested in respiratory muscle monitoring about the current state of the art on sEMG, knowledge gaps and potential future applications for patients with respiratory failure.

Early complications and quality of life in patients with immediately loaded implant-supported maxillary partial rehabilitations: A prospective cohort study.

BACKGROUND: Immediate loading of dental implants is considered an excellent option to reestablish function and aesthetics in a short period of time, thereby reducing the psychological impact of edentulism. The aim of this study was to describe the incidence of complications in immediately loaded implant-supported single or partial maxillary provisional rehabilitations; to assess changes in patient quality of life (QoL); to evaluate patient overall satisfaction; and to determine whether the occurrence of complications affects these outcomes. MATERIAL AND METHODS: Patients requiring partial rehabilitation with implants in the maxilla were included in a prospective cohort study. In all cases, implant-based restoration with an immediate loading protocol was indicated. A provisional restoration was placed within 72 hours after implant placement. Patient QoL was measured at the first appointment and just before placing the final restoration, using two validated questionnaires. All mechanical and biological complications occurring up until placement of the final restoration were documented. A descriptive and bivariate analysis of the data was performed. RESULTS: Thirty-five patients with 40 prostheses supported by 60 implants were analyzed. Three implant failures were observed, yielding a 95% survival rate. Five provisional prosthesis fractures and two prosthetic screw loosenings were recorded in four patients. A significant reduction in OHIP-14 score was observed. Likewise, significant differences were found in the results of the QoLFAST-10, with a mean difference in score of 7.3 between the initial and final evaluation. CONCLUSIONS: Patients receiving immediately loaded implant-supported single or partial maxillary provisional rehabilitations seem to have a low risk of developing early mechanical (13.3%) or biological complications (5%). These patients appear to experience significant improvement in QoL and report excellent overall satisfaction with the treatment received - though the occurrence of complications seems to affect these outcomes.

Has the 8th American joint committee on cancer TNM staging improved prognostic performance in oral cancer? A systematic review.

BACKGROUND: The 8th edition of the American Joint Committee on Cancer (AJCC) classification has introduced two new parameters: depth of invasion (DOI) and extranodal extension (ENE). The aim of this systematic review was to determine whether this 8th edition referred to oral squamous cell carcinoma (OSCC) offers performance superior to that of the 7th edition in relation to overall survival (OS) and disease-specific survival (DSS). MATERIAL AND METHODS: The review was carried out following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. The PubMed (MEDLINE), Scopus and Cochrane Library databases were searched covering the period up until April 7th, 2022. RESULTS: Thirteen retrospective cohort studies were finally included. The introduction of DOI and ENE in the 8th edition of the AJCC classification resulted in improved prognostic performance of the classification. CONCLUSIONS: Patients with OSCC can be better classified in relation to OS and DSS, while maintaining the simplicity and ease of use of the classification. This allows more appropriate treatment protocols to be applied and affords a better estimation of the prognosis of each patient.

Diagnosis and indications for the extraction of third molars - The SECIB clinical practice guideline.

BACKGROUND: The removal of third molars (3Ms) is the most frequent surgical procedure in the field of Oral Surgery. As a result, the Spanish Society of Oral Surgery (SECIB) aims to create a Clinical Practice Guideline (CPG) that offers evidence-based recommendations for optimal clinical practice. Specifically, the CPG will focus on providing guidance regarding the indications and criteria for clinical and radiological diagnosis of patients with 3Ms. MATERIAL AND METHODS: This CPG was developed by the SECIB, following the methodological guidelines described in the methodological manual for the "Development of Clinical Practice Guidelines in the National Health System". Several PICO questions related to the diagnosis and indications for the extraction of 3Ms were formulated. The leading experts carried out the evaluation of the evidence and the formulation of specific recommendations. RESULTS: A total of 17 PICO questions were evaluated, addressing the indications, prognosis, diagnosis, and cost-benefit relationship of 3M extraction. CONCLUSIONS: The present Clinical Practice Guideline provides evidence-based recommendations on the diagnosis and indications for 3M extraction. These evidence-based recommendations can assist healthcare professionals and the general population in making informed decisions regarding the management of 3Ms.

Effect of polygenic risk score, family load of schizophrenia and exposome risk score, and their interactions, on the long-term outcome of first-episode psychosis.

BACKGROUND: Consistent evidence supports the involvement of genetic and environmental factors, and their interactions, in the etiology of psychosis. First-episode psychosis (FEP) comprises a group of disorders that show great clinical and long-term outcome heterogeneity, and the extent to which genetic, familial and environmental factors account for predicting the long-term outcome in FEP patients remains scarcely known. METHODS: The SEGPEPs is an inception cohort study of 243 first-admission patients with FEP who were followed-up for a mean of 20.9 years. FEP patients were thoroughly evaluated by standardized instruments, with 164 patients providing DNA. Aggregate scores estimated in large populations for polygenic risk score (PRS-Sz), exposome risk score (ERS-Sz) and familial load score for schizophrenia (FLS-Sz) were ascertained. Long-term functioning was assessed by means of the Social and Occupational Functioning Assessment Scale (SOFAS). The relative excess risk due to interaction (RERI) was used as a standard method to estimate the effect of interaction of risk factors. RESULTS: Our results showed that a high FLS-Sz gave greater explanatory capacity for long-term outcome, followed by the ERS-Sz and then the PRS-Sz. The PRS-Sz did not discriminate significantly between recovered and non-recovered FEP patients in the long term. No significant interaction between the PRS-Sz, ERS-Sz or FLS-Sz regarding the long-term functioning of FEP patients was found. CONCLUSIONS: Our results support an additive model of familial antecedents of schizophrenia, environmental risk factors and polygenic risk factors as contributors to a poor long-term functional outcome for FEP patients.

The role of Human Development Index in the epidemiology of asthma in adolescents in Kosovo: A cross-sectional multicentre Global Asthma Network (GAN) study.

BACKGROUND: Very limited information is available on the prevalence and risk factors of asthma in adolescents in Kosovo, and no study has previously addressed the role of Human Development Index (HDI) on asthma in the region. The present study addresses these two issues. METHODS: Following the Global Asthma Network (GAN) methodology, a cross-sectional survey, through standardised self-completed questionnaires, was conducted in the following six centres of Kosovo: Ferizaj, Gjakova, Gjilan, Peja, Prishtina and Prizren. Current asthma symptoms (CAS) and severe current asthma symptoms (sCAS) were defined according to the GAN standards. Environmental questionnaire inquired about gender, exercise, screening time, siblings, truck traffic, use of paracetamol, pet ownership, and smoking habits. Height and weight were also measured. Multivariate logistic regression analyses were performed in each centre along with meta-analyses to summarise the overall effects of each factor in the centres as a whole. Meta-regression of the prevalence rates was calculated using HDI as a moderator. RESULTS: Participation rate was high (80.0-99.9%). Prevalence of CAS ranged from 4.6% to 11.3%, and sCAS from 1.7% to 4.5%. Factors associated with CAS were exercise, computer time, paracetamol use and dog ownership. sCAS was associated with paracetamol use and physical exercise. HDI explained 46% and 80% of prevalence variability of CAS and sCAS between centres, respectively. CONCLUSIONS: Prevalence of CAS and sCAS in Kosovo varies highly between centres. This variability is explained partly by HDI. Individual risk factors are common, with some determined in other studies conducted in other regions.

Relationship between cognition and age at onset of first-episode psychosis: comparative study between adolescents, young adults, and adults.

Psychotic disorders typically manifest from late adolescence to early adulthood, and an earlier onset might be associated with greater symptom severity and a worse long-term prognosis. This study aimed to compare the cognitive characteristics of patients with first-episode psychosis (FEP) by their age at onset. We included 298 patients diagnosed with FEP and classified them as having an early onset (EOS), youth onset (YOS), or adult onset (AOS) based on age limits of ≤ 18 years (N = 61), 19-24 years (N = 121), and ≥ 25 years (N = 116), respectively. Socio-demographic and clinical variables included age at baseline, gender, socio-economic status, antipsychotic medication, DSM-IV diagnoses assessed by clinical semi-structured interview, psychotic symptom severity, and age at onset. Neuropsychological assessment included six cognitive domains: premorbid intelligence, working memory, processing speed, verbal memory, sustained attention, and executive functioning. The EOS group had lower scores than the YOS or AOS groups in global cognition, executive functioning, and sustained attention. Although the scores in the YOS group were intermediate to those in the EOS and AOS groups for most cognitive factors, no statistically significant differences were detected between the YOS and AOS groups. Age at onset results in specific patterns of cognitive interference. Of note, impairment appears to be greater with EOS samples than with either YOS or AOS samples. A longitudinal study with a larger sample size is needed to confirm our findings.

Comparative analysis of risk factors for COVID-19 mortality before, during and after the vaccination programme in Mexico.

OBJECTIVES: The purpose of this study was to compare case fatality rates (CFRs) and odds for mortality by risk factors of patients with COVID-19 in Mexico, before, during and after the implementation of the national COVID-19 vaccination programme. STUDY DESIGN: A large database including COVID-19 monitoring cases was used to perform an observational retrospective study. METHODS: The Chi-squared test and multivariate logistic regression analyses were applied to data from COVID-19-positive patients in Mexico. Data were analysed over 3 years, 2020, 2021 and 2022, corresponding with pre-, during and post-vaccination periods. The unadjusted odds ratios and 95% confidence interval were used to estimate the risk factors for COVID-19 mortality in each of the years. RESULTS: Statistically significant differences in CFR and odds ratio were found in the studied years, favouring postvaccination period. Significant changes in CFR by age, sex and main comorbidities indicated changes in the epidemic dynamics after the implementation of the COVID-19 vaccination campaign. The likelihood of death increased for hospitalised cases and for patients who were middle-aged or older in 2021 and 2022, whereas the odds of death associated with sex and comorbidities remained similar or reduced over the 3 years. CONCLUSIONS: Implementation of the COVID-19 vaccination programme during 2021 showed positive consequences on CFR. The increased odds of dying in hospitalised patients are likely to be due to the unvaccinated proportion of patients.

Clinical evaluation of subcutaneous immunotherapy with a polymerized molecular allergoid of Alt a 1 in patients with allergic rhinoconjunctivitis and/or allergic asthma caused by the mould Alternaria alternata.

Summary: This is a retrospective analysis of the clinical evolution of 14 patients diagnosed with allergic rhinoconjunctivitis (AR) and/or allergic asthma (AA) caused by Alternaria alternata, who were attended by the allergology service of Vega Baja Hospital of Orihuela (Alicante, Spain). The purpose was to assess the clinical impact and safety of 1-year of subcutaneous immunotherapy with a polymerized molecular allergoid of Alt a 1. Impact of the treatment on allergic diseases (mean number AR/AA episodes and ARIA/GINA classifications), changes in symptoms and prescribed medication, change in the global subjective clinical status of patients and satisfaction with the treatment were also evaluated. Adverse reactions were also recorded and analyzed. After 1-year of treatment, fewer AR and AA episodes (p less than 0.05) and improvements in ARIA/GINA classifications were observed. Significant improvements of symptoms (p less than 0.05) and a resulting general reduction of the medication prescribed was also detected. Improvements in the global subjective clinical status and good satisfaction rates were observed. Only 1 patient presented a local and not clinically relevant adverse reaction. The treatment showed promising effects with a significant improvement in the clinical status of all patients with a good safety profile.

Predictors of surgical difficulty in upper third molar removal: a prospective cohort study.

BACKGROUND: Upper third molar (U3M) removal is a common surgical procedure. The aims of this study were to assess the patient-specific, radiological and surgical factors related to the difficulty of U3M removal, and to determine the incidence of intraoperative and postoperative complications. MATERIAL AND METHODS: A prospective cohort study was carried out in adult patients undergoing U3M removal. Operative time, surgeon-reported difficulty and the Parant classification were used to assess extraction difficulty. Clinical, radiological and surgical factors were recorded to determine their relationship with surgical difficulty. A descriptive, bivariate and multivariate statistical analysis was carried out. RESULTS: A total of 250 patients were included. The mean operative time was 10.4 (±12.3) minutes, mean surgeon-reported difficulty was 3.2/10 (±2.3). The multivariate analysis showed greater impaction against the second molar and greater soft tissue and bony impaction to significantly increase operative time and surgeon-perceived difficulty. Additionally, surgeon experience was related to perceived difficulty. The overall incidence of intraoperative complications was 0.8%, and no postoperative events were recorded. CONCLUSIONS: Upper third molars in close relation with the roots of the adjacent second molar and with soft tissue and bony impaction are significantly more difficult to extract. Perceived difficulty was related to surgeon experience. This procedure appears to produce few intra- and postoperative complications.

The burden of asthma, hay fever and eczema in children in 25 countries: GAN Phase I study.

AIMS: There have been no worldwide standardised surveys of prevalence and severity of asthma, rhinoconjunctivitis and eczema in school children for 15 years. The present study aims to provide this information. METHODS: Following the exact International Study of Asthma and Allergies in Childhood (ISAAC) methodology (cross-sectional questionnaire-based survey), Global Asthma Network (GAN) Phase I was carried out between 2015 and 2020 in many centres worldwide. RESULTS: The study included 157 784 adolescents (13-14 years of age) in 63 centres in 25 countries and 101 777 children (6-7 years of age) in 44 centres in 16 countries. The current prevalence of symptoms, respectively, was 11.0% and 9.1% for asthma, 13.3% and 7.7% for rhinoconjunctivitis and 6.4% and 5.9% for eczema. The prevalence of asthma ever was 10.5% and 7.6%, hay fever ever was 15.2% and 11.1% and eczema ever was 10.6% and 13.4%, respectively. Centres in low or lower middle gross national income countries (LICs or LMICs) had significantly lower prevalence of the three disease symptoms and diagnoses (except for hay fever). In children, the prevalence of asthma and rhinoconjunctivitis symptoms was higher in boys, while the reverse occurred among adolescents. For eczema, while the prevalence among female adolescents was double that of males, there was no sex difference among children. Centre accounted for non-negligible variability in all disease symptoms (10-20%). CONCLUSION: The burdens of asthma, rhinoconjunctivitis and eczema vary widely among the limited number of countries studied. Although symptom prevalence is lower in LICs and LMICs, it represents a considerable burden everywhere studied.

Third molar surgical difficulty scales: systematic review and preoperative assessment form.

BACKGROUND: The main objective of this systematic review was to collect the pre-existing scales for assessing the difficulty of third molar extraction. The secondary objective was to design a proposal for a preoperative evaluation protocol for the difficulty of third molar extraction. MATERIAL AND METHODS: Two independent researchers conducted an electronic search in Pubmed (MEDLINE), Cochrane, and Scopus databases during March 2021. Included studies evaluated the prediction of the difficulty of surgical removal of impacted upper or lower third molars using new indices/scales or pre-existing scales with or without modifications. Articles referring to coronectomies or assessing pre-surgical difficulty using other tools were excluded. Neither language nor publication date restrictions were applied. RESULTS: Out of 242 articles, 13 prospective cohort studies were finally selected. Seven developed new indices/scales, and 6 assessed the predictive ability of some pre-existing scales. Most of the indices/scales contained radiological variables and few added any patient-related variables. We proposed a preoperative assessment protocol of the difficulty of third molar extraction to facilitate treatment planning and/or considerate referral in cases of high difficulty. This proposal used patient-related, radiological and surgical variables. CONCLUSIONS: Using a preoperative protocol to evaluate the surgical difficulty, including different patient-specific, radiological and surgical variables, could facilitate treatment planning, help clinicians prevent complications and assess the possibility of referral.

Alterations in the non-neuronal cholinergic system induced by in-vitro exposure to diazoxon in spleen mononuclear cells of Nile tilapia (O. niloticus).

Organophosphate pesticides as diazinon disrupt the neuroimmune communication, affecting the innate and adaptive immune response of the exposed organisms. Since the target molecule of diazinon is typically the acetylcholinesterase enzyme (AChE), the existence of a non-neuronal cholinergic system in leukocytes makes them susceptible to alterations by diazinon. Therefore, the aim of this work was to evaluate the activity of AChE, acetylcholine (ACh) concentration, and the expression of nicotinic ACh receptors (nAChR) and muscarinic ACh receptors (mAChR) in spleen mononuclear cells (SMNC) of Nile tilapia (O. niloticus) exposed in vitro to diazoxon, a diazinon metabolite. SMNC were exposed in-vitro to 1 nM, 1 µM, and 10 µM diazoxon for 24 h. The enzyme activity of AChE was then evaluated by spectrophotometry, followed by ACh quantification by ultra-performance liquid chromatography. Finally, mAChR and nAChR expression was evaluated by RT-qPCR. The results indicate that AChE levels are significantly inhibited at 1 and 10 µM diazoxon, while the relative expression of (M3, M4, and M5) mAChR and (ß2) nAChR is reduced significantly as compared against SMNC not exposed to diazoxon. However, ACh levels show no significant difference with respect to the control group. The data indicate that diazoxon directly alters elements in the cholinergic system of SMNC by AChE inhibition or indirectly through the interaction with AChR, which is likely related to the immunotoxic properties of diazinon and its metabolites.

Real-world corticosteroid use in severe pneumonia: a propensity-score-matched study.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide despite correct antibiotic use. Corticosteroids have long been evaluated as a treatment option, but heterogeneous effects on survival have precluded their widespread implementation. We aimed to evaluate whether corticosteroids might improve clinical outcomes in patients with severe CAP and high inflammatory responses. STUDY DESIGN AND METHODS: We analyzed two prospective observational cohorts of patients with CAP in Barcelona and Rome who were admitted to intensive care with a high inflammatory response. Propensity score (PS) matching was used to obtain balance among the baseline variables in both groups, and we excluded patients with viral pneumonia or who received hydrocortisone. RESULTS: Of the 610 patients admitted with severe CAP, 198 (32%) received corticosteroids and 387 had major criteria for severe CAP. All patients had a baseline serum C-reactive protein above 15 mg/dL. Patients who received corticosteroids were more commonly male, had more comorbidities (e.g., cancer or chronic obstructive pulmonary disease), and presented with significantly higher sequential organ failure assessment scores. Eighty-nine patients met major severity criteria (invasive mechanical ventilation and/or septic shock) and were matched per group. Twenty-eight-day mortality was lower among patients receiving corticosteroids (16 patients, 18%) than among those not receiving them (28 patients, 31%; p = 0.037). After PS matching, corticosteroid therapy reduced the 28-day mortality risk in patients who met major severity criteria (hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.29-0.98) (p = 0.043). In patients who did not meet major severity criteria, no benefits were observed with corticosteroid use (HR 0.88 (95%CI 0.32-2.36). CONCLUSIONS: Corticosteroid treatment may be of benefit for patients with CAP who have septic shock and/or a high inflammatory response and requirement for invasive mechanical ventilation. Corticosteroids appear to have no impact on mortality when these features are not present.

Outcomes After Vascular Surgery Procedures in Patients with COVID-19 Infection: A National Multicenter Cohort Study (COVID-VAS).

OBJECTIVES: To analyze the outcome of vascular procedures performed in patients with COVID-19 infection during the 2020 pandemic. METHODS: This is a multicenter, prospective observational cohort study. We analyzed data from 75 patients with COVID-19 infection undergoing vascular surgery procedures in 17 hospitals across Spain and Andorra between March and May 2020. The primary end point was 30-day mortality. Clinical Trials registry number NCT04333693. RESULTS: The mean age was 70.9 (45-94) and 58 (77.0%) patients were male. Around 70.7% had postoperative complications, 36.0% of patients experienced respiratory failure, 22.7% acute renal failure, and 22.7% acute respiratory distress syndrome (ARDS). All-cause 30-days mortality rate was 37.3%. Multivariate analysis identified age >65 years (P = 0.009), American Society of Anesthesiologists (ASA) classification IV (P = 0.004), preoperative lymphocyte count <0.6 (×109/L) (P = 0.001) and lactate dehydrogenase (LDH) >500 (UI/L) (P = 0.004), need for invasive ventilation (P = 0.043), postoperative acute renal failure (P = 0.001), ARDS (P = 0.003) and major amputation (P = 0.009) as independent variables associated with mortality. Preoperative coma (P = 0.001), quick Sepsis Related Organ Failure Assessment (qSOFA) score ≥2 (P = 0.043), lymphocytes <0.6 (×109/L) (P = 0.019) leucocytes >11.5 (×109/L) (P = 0.007) and serum ferritin >1800 mg/dL (P = 0.004), bilateral lung infiltrates on thorax computed tomography (P = 0.025), and postoperative acute renal failure (P = 0.009) increased the risk of postoperative ARDS. qSOFA score ≥2 was the only risk factor associated with postoperative sepsis (P = 0.041). CONCLUSIONS: Patients with COVID-19 infection undergoing vascular surgery procedures showed poor 30-days survival. Age >65 years, preoperative lymphocytes <0.6 (x109/L) and LDH >500 (UI/L), and postoperative acute renal failure, ARDS and need for major amputation were identified as prognostic factors of 30-days mortality.

The influence of the correlation-covariance structure of measurement errors over uncertainties propagation in online monitoring: application to environmental indicators in SUDS.

This paper presents a methodology to assess the influence of the correlation-covariance structure of measurement errors in online monitoring over the propagation of uncertainties, applied to wet-weather environmental indicators in sustainable urban drainage systems (SUDSs). The effect of auto-correlated and heteroskedastic errors in measured time-series over the estimated probability density function (PDF) of different environmental indicators is analyzed for a wide variety of possible error structures in the data. For this purpose, multiple correlation-covariance structures are randomly generated from exploring the parametric space of a linear exponent autoregressive (LEAR) model, employing a Bayesian-based Markov Chain Monte Carlo sampling technique. Significant differences tests are proposed to identify the most correlated parameters of the correlation-covariance error model with statistics of the environmental indicator PDFs. The method is applied to total suspended solids (TSS) and chemical oxygen demand (COD) time-series recorded during 13 rainfall events at the inlet and outlet of a SUDS train (stormwater settling tank-horizontal constructed wetland). In this case, results showed that the total error in the estimation of the analyzed environmental indicators is mostly explained by standard uncertainties (flattening of the PDFs) rather than bias contributions (displacement of the PDFs). The correlation-covariance model parameters related to the temporal delimitation of hydrographs/pollutographs and the intensity of the autocorrelation showed to have the strongest influence in the propagation of measurement errors (flattening/displacement of the PDFs).

Retrograde filling material in periapical surgery: a systematic review.

BACKGROUND: Periapical surgery focuses on the treatment of teeth with persistent periapical lesions when orthograde root canal treatment fails. Although MTA® is the gold standard material for retrograde filling, Biodentine® - a tricalcium silicate-based cement - has been proposed in order to resolve several of its limitations. A systematic review has been carried out to compare the physicochemical properties of Biodentine® versus MTA® as root-end filling material in periapical surgery. MATERIAL AND METHODS: An electronic search was conducted by two independent examiners during March 2020 in the Cochrane, PubMed-MEDLINE and Scopus databases. In addition, a manual search was made in specialized journals. Comparative human or in vitro studies that evaluated bond strength, the presence of marginal gap and sealing ability were included. No restriction on publication date was applied. Animal studies, clinical cases, cases series and expert opinions were excluded. RESULTS: After analyzing 147 initially selected studies, 13 publications were included. Regarding bond strength, the studies seemed to evidence better performance of Biodentine® in both acidic and blood contaminated environments. In relation to the presence of marginal gap and sealing ability, the studies yielded contradictory results. According to some authors, the sealing ability of Biodentine® is greater than that of MTA® during the first 24 hours, though both materials prove equal after one week. Other authors recorded no significant differences. CONCLUSIONS: Considering the limitations and heterogeneity of the studies included, there is not sufficient evidence to confirm the clinical superiority of Biodentine® as a root-end filling material in periapical surgery.

Efficacy of Telavancin in Comparison to Linezolid in a Porcine Model of Severe Methicillin-Resistant Staphylococcus aureus Pneumonia.

Current guidelines recommend vancomycin and linezolid as first-line agents against methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. Telavancin is a potential new therapeutic alternative, specifically in monomicrobial MRSA pneumonia. This study compared the efficacies of telavancin versus linezolid in a porcine model of severe MRSA pneumonia. In 18 mechanically ventilated pigs (32.11 ± 1.18 kg), 75 ml of 106 CFU/ml of MRSA was administered into each pulmonary lobe. After the onset of pneumonia, pigs were randomized into three groups: a control group, a group receiving 22.5 mg/kg of body weight every 24 h (q24h) of telavancin, and a group receiving 10 mg/kg q12h of linezolid intravenously. Tracheal aspirate and bronchoalveolar lavage (BAL) fluids were cultured every 24 h. After 48 h of treatment, tissue samples were collected from the ventral and dorsal sections of each lobe. Microbiological and histopathological analyses were performed. Lung tissue concentrations differed among the groups (P = 0.019), with the lowest MRSA lung burden in the telavancin group (P < 0.05 versus the control). MRSA was detected in 46.7%, 40.0%, and 21.7% of the lung tissue samples from the control, linezolid, and telavancin groups, respectively (P < 0.001). MRSA concentrations differed among the groups in tracheal aspirate fluid (P = 0.011) but not in BAL fluid. Furthermore, there was no increased risk of kidney injury during telavancin use. Thus, telavancin has higher bactericidal efficacy than linezolid during the first 48 h of treatment in a porcine model of severe MRSA pneumonia. However, studies are needed to confirm the benefits of telavancin in treating MRSA nosocomial pneumonia.

Origin of cell contrast in offset aperture adaptive optics ophthalmoscopy.

Offset aperture and split detector imaging are variants of adaptive optics scanning ophthalmoscopy recently introduced to improve the image contrast of retinal cells. Unlike conventional confocal scanning ophthalmoscopy, these approaches collect light laterally decentered from the optical axis. A complete explanation of how these methods enhance contrast has not been described. Here, we provide an optical model with supporting in vivo data that show contrast is generated from spatial variations in the refractive index as it is in phase contrast microscopy. A prediction of this model is supported by experimental data that show contrast is optimized when the detector is placed conjugate with a deeper backscattering screen such as the retinal pigment epithelium and choroid, rather than with the layer being imaged as in conventional confocal imaging. This detection strategy provides a substantial improvement in the contrast these new methods can produce.