Proteomic profile of human gingival crevicular fluid reveals specific biological and molecular processes during clinical progression of periodontitis.

BACKGROUND AND OBJECTIVE: There is no clear understanding of molecular events occurring in the periodontal microenvironment during clinical disease progression. Our aim was to explore qualitative and quantitative differences in gingival crevicular fluid (GCF) protein profiles from patients diagnosed with periodontitis between non-progressive and progressive periodontal sites. METHODS: Five systemically healthy patients diagnosed with periodontitis were monitored weekly in their progression of the disease and GCF samples from 10 candidate sites were obtained. Two groups of five sites, matched from an equal number of teeth, were selected from the five patients: Progression (PG) and Non-Progression (NP). Global protein identification was performed with high-throughput proteomic approaches and label-free analysis determined their relative abundances. Proteins were identified by Proteome Discoverer v2.4 and searched against human SwissProt protein databases. Enrichment bioinformatic analyses were performed in STRING-DB and ShinyGO environment. RESULTS: 1504 and 1500 proteins were identified in NP and PG respectively. Forty-eight proteins were exclusively identified in PG, while 52 were identified in NP. Moreover, 35 proteins were more abundant in PG and 29 proteins in NP (twofold change, p < .05). The NP group was mainly represented by proteins from "response to biotic stimuli and other organisms," "processes of cell death regulation," "peptidase regulation," "protein ubiquitination," and "ribosomal activity" GO categories. The most represented GO categories of the PG group were "assembly of multiprotein complexes," "catabolic processes," "lipid metabolism," and "binding to hemoglobin and haptoglobin." CONCLUSIONS: There are quantitative and qualitative differences in the proteome of GCF from periodontal sites according to the status of clinical progression of periodontitis. Progressive periodontitis sites are characterized by a protein profile associated with catabolic processes, immune response, and response to cellular stress, while stable periodontitis sites show a protein profile mainly related to wound repair and healing processes, cell death regulation, and chaperone-mediated autophagy. Understanding the etiopathogenic role of these profiles in progressive periodontitis may help to develop new diagnostic and therapeutic approaches.

Clinical effects of probiotic or azithromycin as an adjunct to scaling and root planning in the treatment of stage III periodontitis: a pilot randomized controlled clinical trial.

BACKGROUND: The aim of this triple-blind placebo-controlled parallel-arm randomized clinical trial was to evaluate the clinical effects of Lactobacillus rhamnosus SP1 or azithromycin as an adjunct to scaling and root planing (SRP) in patients with stage III periodontitis. METHODS: Forty-seven systemically healthy participants with stage III periodontitis were recruited. Following SRP, the participants were randomly assigned to one of three treatment modalities; (1) placebo (n = 15), (2) probiotics (n = 16) and (3) antibiotics-azithromycin (n = 16). The participants were monitored at baseline, 3, 6, 9 and 12 months after therapy. Probing pocket depth (PPD), bleeding on probing (BOP), clinical attachment loss (CAL) and plaque accumulation (PI) were evaluated. RESULTS: All 47 participants completed the study. At 12 months, all groups showed significant improvements of PPD and PI (p < 0.012) irrespective of the treatment modality and without significant differences between the groups. Probiotics and azithromycin showed no added benefit in terms of CAL. While the placebo (p = 0.002) and the antibiotic-azithromycin (p = 0.002) group showed a significant reduction of BOP, only the placebo group revealed a significant reduction of CAL at 12 months follow-up (p = 0.003). The number of sites and teeth with PPD ≥ 5, ≥ 6 and ≥ 7 mm were significantly reduced in all groups at 12 months follow-up (p < 0.025) irrespective of the treatment regime and without significant differences between the groups. CONCLUSION: The use of probiotics or azithromycin as an adjunct to SRP failed to provide additional benefits in the treatment of stage III periodontitis. The benefits of these two treatment regimes as an adjunct to SRP remain unclear. TRIAL REGISTRATION: NCT02839408, 10/28/2017, Clinicaltrial.gov.

Preclinical development of T-cell receptor-engineered T-cell therapy targeting the 5T4 tumor antigen on renal cell carcinoma.

5T4 (trophoblast glycoprotein, TPBG) is a transmembrane tumor antigen expressed on more than 90% of primary renal cell carcinomas (RCC) and a wide range of human carcinomas but not on most somatic adult tissues. The favorable expression pattern has encouraged the development and clinical testing of 5T4-targeted antibody and vaccine therapies. 5T4 also represents a compelling and unexplored target for T-cell receptor (TCR)-engineered T-cell therapy. Our group has previously isolated high-avidity CD8+ T-cell clones specific for an HLA-A2-restricted 5T4 epitope (residues 17-25; 5T4p17). In this report, targeted single-cell RNA sequencing was performed on 5T4p17-specific T-cell clones to sequence the highly variable complementarity-determining region 3 (CDR3) of T-cell receptor α chain (TRA) and ß chain (TRB) genes. Full-length TRA and TRB sequences were cloned into lentiviral vectors and transduced into CD8+ T-cells from healthy donors. Redirected effector T-cell function against 5T4p17 was measured by cytotoxicity and cytokine release assays. Seven unique TRA-TRB pairs were identified. All seven TCRs exhibited high expression on CD8+ T-cells with transduction efficiencies from 59 to 89%. TCR-transduced CD8+ T-cells demonstrated redirected cytotoxicity and cytokine release in response to 5T4p17 on target-cells and killed 5T4+/HLA-A2+ kidney-, breast-, and colorectal-tumor cell lines as well as primary RCC tumor cells in vitro. TCR-transduced CD8+ T-cells also detected presentation of 5T4p17 in TAP1/2-deficient T2 target-cells. TCR-transduced T-cells redirected to recognize the 5T4p17 epitope from a broadly shared tumor antigen are of interest for future testing as a cellular immunotherapy strategy for HLA-A2+ subjects with 5T4+ tumors.

Dental caries is associated with severe periodontitis in Chilean adults: a cross-sectional study.

BACKGROUND: The co-occurrence of caries and periodontitis and a possible association is still a matter of debate. Thus, the aim of the study was to determine the co-occurrence of caries and periodontitis in Chilean adults. METHODS: Evaluation of periodontal and dental status in 994 adults (35-44 years old) based on the First Chilean National Examination Survey 2007-2008. The prevalence of caries was defined as the percentage of participants with one or more teeth with untreated caries by using the D component of the DMFT index (DT ≠ 0). The prevalence of periodontitis was determined using standard case definitions for population-based surveillance of periodontitis described by the CDC-AAP. RESULTS: Individuals with caries had an approximately 40% higher prevalence of severe (29.3% vs 20.8%, p < 0.05) and a 13% higher prevalence of total periodontitis (89.3% vs 78.4%, p < 0.05) than those without caries. Ordinal logistic regression revealed a positive association between periodontitis and the number of teeth with caries (DT ≠ 0; 3 or 4 teeth with caries: OR 1.74; CI = 1.12-2.29 p < 0.05; 5 or more teeth with caries: OR 2.47; CI = 1.66-3.67 p < 0.01). CONCLUSION: Dental caries is associated with the severity and prevalence of periodontitis in Chilean adults. Individuals with 3 or more teeth with untreated caries are more likely to suffer from periodontal disease.

Prevalence and predictors for clinical attachment loss in adolescents in Latin America: cross-sectional study.

AIM: To describe the prevalence, severity and extension of clinical attachment loss (CAL) and to study the predictors in 15- to 19-year-old adolescents from high schools in the Latin America. MATERIALS AND METHODS: A cross-sectional, epidemiological study was performed. The sample included 1070 high school adolescents 15-19 years of age from Santiago de Chile (Chile), Buenos Aires, Córdoba, Mendoza (Argentina), Montevideo (Uruguay), Quito (Ecuador) and Medellín (Colombia). Calibrated examiners performed full mouth, six sites per tooth clinical examination. RESULTS: There was a response rate of 100%. The prevalence of CAL ≥3 mm in ≥1 site was 32.6%, probing pocket depth ≥4 mm was 59.3% and bleeding on probing (BoP) ≥25% was 28.6%. The logistic regression analysis adjusted for cities revealed that smoking (OR = 1.6), attending public school (OR = 2.3) and having a BoP ≥25% (OR = 4.2) were positively associated with CAL ≥3 mm in ≥ 1 site. CONCLUSION: Clinical attachment loss was prevalent in Latin America adolescents and it is associated with smoking, attendance public school and BoP.

A multi-platform analysis of human gingival crevicular fluid reveals ferroptosis as a relevant regulated cell death mechanism during the clinical progression of periodontitis.

Ferroptosis is implicated in the pathogenesis of numerous chronic-inflammatory diseases, yet its association with progressive periodontitis remains unexplored. To investigate the involvement and significance of ferroptosis in periodontitis progression, we assessed sixteen periodontitis-diagnosed patients. Disease progression was clinically monitored over twelve weeks via weekly clinical evaluations and gingival crevicular fluid (GCF) collection was performed for further analyses. Clinical metrics, proteomic data, in silico methods, and bioinformatics tools were combined to identify protein profiles linked to periodontitis progression and to explore their potential connection with ferroptosis. Subsequent western blot analyses validated key findings. Finally, a single-cell RNA sequencing (scRNA-seq) dataset (GSE164241) for gingival tissues was analyzed to elucidate cellular dynamics during periodontitis progression. Periodontitis progression was identified as occurring at a faster rate than traditionally thought. GCF samples from progressing and non-progressing periodontal sites showed quantitative and qualitatively distinct proteomic profiles. In addition, specific biological processes and molecular functions during progressive periodontitis were revealed and a set of hub proteins, including SNCA, CA1, HBB, SLC4A1, and ANK1 was strongly associated with the clinical progression status of periodontitis. Moreover, we found specific proteins - drivers or suppressors - associated with ferroptosis (SNCA, FTH1, HSPB1, CD44, and GCLC), revealing the co-occurrence of this specific type of regulated cell death during the clinical progression of periodontitis. Additionally, the integration of quantitative proteomic data with scRNA-seq analysis suggested the susceptibility of fibroblasts to ferroptosis. Our analyses reveal proteins and processes linked to ferroptosis for the first time in periodontal patients, which offer new insights into the molecular mechanisms of progressive periodontal disease. These findings may lead to novel diagnostic and therapeutic strategies.

Performance of the 2017 AAP/EFP case definition compared with the CDC/AAP definition in population-based studies.

BACKGROUND: Classification of the periodontal conditions is indispensable for epidemiological data in order to guide situational awareness and therapeutic strategies. The new classification of periodontal diseases and conditions introduced by the American Academy of Periodontology and the European Federation of Periodontology (AAP/EFP), however, has not yet been applied to population-based studies. The aim of the present study was to compare the prevalence of periodontitis between the AAP/EFP and the CDC/AAP classification system and to evaluate the accuracy of the new AAP/EFP classification system against the CDC/AAP case definition for population-based studies. METHODS: Epidemiological data from two cross-sectional studies were obtained. One of them was a population-based study on Chilean adults (1.456 individuals; 35-44 years; 65-74 years) and the other one a sample of adolescents (1.070 individuals; 15-19 years) from five countries; Argentina, Chile, Colombia, Ecuador, and Uruguay. All participants had undergone full-mouth periodontal examination by calibrated examiners. Epidemiological datasets were analyzed according to the AAP/EFP and the CDC/AAP case definitions. The accuracy of the AAP/EFP definition was examined by assessing the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating curve (ROC) using the CDC/AAP case definition as the reference standard. RESULTS: According to the AAP/EFP, the prevalence of periodontitis in adolescents was 75.6%. The majority of the adolescents were classified either as Stage I (39.2%) or Stage II (28.2%). By using the CDC/AAP classification the prevalence of periodontitis in adolescents was 27.2%. The most common form of periodontitis with the CDC/AAP classification was moderate periodontitis (15.3%) followed by mild periodontitis (11.4%). The AAP/EFP revealed high sensitivity in moderate (95.7%) and severe periodontitis (100%) as well as a moderate (75%) to high specificity (92%) in moderate and severe periodontitis, respectively. The PPV was 41.6% in moderate and 5.7% in severe periodontitis whereas the NPV was high in both categories (moderate = 99%; severe = 100%). The AUC was 0.91 (95% CI = 0.89-0.93). In adults, the prevalence of periodontitis was 99% according to the AAP/EFP. The majority of adults were classified as Stage IV (81.3%) whereas Stage III amounted to 12.8%. By using the CDC/AAP classification, the prevalence of periodontitis in adults was 88.3% and the most common form of periodontitis was moderate periodontitis (57.2%) followed by severe periodontitis (29.7%). In adults, the AAP/EFP revealed high sensitivity for moderate (99.7%) and severe periodontitis (100%), but low specificity for both categories (moderate = 6.8%; severe = 8.3%). The PPV was 88.7% in moderate and 31.7% in severe periodontitis. The NPV was high in both categories (moderate = 76.5%; severe = 100%). The AUC was 0.57 (95% CI = 0.53-0.62). CONCLUSIONS: This study revealed a clear discrepancy in the prevalence of periodontitis between the AAP/EFP and the CDC/AAP classification when using epidemiological data. The 2017 AAP/EFP classification system performs well when compared to the CDC/AAP case definition in identifying adolescents with periodontitis. The AAP/EFP system seems less accurate in adults with high prevalence of periodontitis.

Integrated TCR repertoire analysis and single-cell transcriptomic profiling of tumor-infiltrating T cells in renal cell carcinoma identifies shared and tumor-restricted expanded clones with unique phenotypes.

Objective responses of metastatic renal cell carcinoma (RCC) associated with systemic immunotherapies suggest the potential for T-cell-mediated tumor clearance. Recent analyses associate clonally expanded T cells present in the tumor at diagnosis with responses to immune checkpoint inhibitors (ICIs). To identify and further characterize tumor-associated, clonally expanded T cells, we characterized the density, spatial distribution, T-cell receptor (TCR) repertoire, and transcriptome of tumor-infiltrating T cells from 14 renal tumors at the time of resection and compared them with T cells in peripheral blood and normal adjacent kidney. Multiplex immunohistochemistry revealed that T-cell density was higher in clear cell RCC (ccRCC) than in other renal tumor histologies with spatially nonuniform T-cell hotspots and exclusion zones. TCR repertoire analysis also revealed increased clonal expansion in ccRCC tumors compared with non-clear cell histologies or normal tissues. Expanded T-cell clones were most frequently CD8+ with some detectable in peripheral blood or normal kidney and others found exclusively within the tumor. Divergent expression profiles for chemokine receptors and ligands and the Ki67 proliferation marker distinguished tumor-restricted T-cell clones from those also present in blood suggesting a distinct phenotype for subsets of clonally expanded T cells that also differed for upregulated markers of T-cell activation and exhaustion. Thus, our single-cell level stratification of clonally expanded tumor infiltrating T-cell subpopulations provides a framework for further analysis. Future studies will address the spatial orientation of these clonal subsets within tumors and their association with treatment outcomes for ICIs or other therapeutic modalities.

Developing a protocol for a preventive oral health exam for elderly people (EDePAM) using E-Delphi methodology.

The aim of this study was to develop a Preventive Oral Health Exam for Elderly People (EDePAM), using the e-Delphi technique, to diagnose oral health problems in people 65 or older. The e-Delphi technique was used with experts in multiple stages, and in a final workshop, where an agreement on an examination protocol was reached for diagnosing dental caries, oral mucosa lesions, periodontal diseases, and masticatory function disorders. Quantitative analyses of all the rounds of the e-Delphi method were conducted. It was agreed that the International Caries Detection and Assessment System (ICDAS) should be used together with a modified version of the Nyvad criteria to detect and assess caries lesions. It was also agreed that an assessment was needed of the different factors involved in determining caries risk, namely socioeconomic level, access to fluoride, level of dependence/functionality, salivary flow, history of head and neck cancer treatment, use of medications that decrease salivary flow, diet, use of removable dental prostheses, exposure of root surfaces, and caries history. Furthermore, patients would be required to undergo an examination of the oral mucosa, where any existing lesion should be described in terms of its clinical appearance, location, and risk potential. It was also agreed that an assessment of masticatory function should be performed using the Leake index, together with chewing-gum combined with a color scale to categorize masticatory performance. The number of pairs of occluding antagonist teeth was considered as the best predictor of masticatory function. The 2018 classification by the American Academy of Periodontology (AAP) / European Federation of Periodontology (EFP) was accepted as the standard to assess periodontal status, and it was agreed that this assessment should include an evaluation of clinical attachment loss and bleeding on probing. The novel EDePAM was considered as appropriate for conducting a functional assessment of oral health by providing a comprehensive diagnosis of oral diseases.

RNA helicase, DDX3X, is actively recruited to sites of DNA damage in live cells.

Recent studies have suggested that human RNA helicase, DDX3X, is important for DNA repair, but little is known about the nuclear activity of this protein. In vitro analysis of nuclear DDX3X interactions and localization with DNA damage pointed to a direct role for DDX3X in the DNA damage response. We aimed to investigate whether DDX3X plays a direct role in the DNA damage response in live cells. In order to track nuclear DDX3X, we generated a nuclear-export deficient DDX3X mutant construct and performed microirradiation in live cells. We found that DDX3X accumulates at sites of microirradiation shortly after DNA damage induction. We further found DDX3X recruitment to be mediated by its intrinsically disordered domains, similar to other RNA binding proteins that are recruited to sites of DNA damage. Inhibition of liquid-liquid phase separation also reduced DDX3X recruitment. CRISPR/Cas9-mediated knockout of PARP1 ablated DDX3X recruitment, which was restored upon transgenic expression of wild-type PARP1 but not catalytically inactive PARP1, suggesting that DDX3X recruitment is PARP1-dependent.

Comparison Between Pressure Swing Adsorption and Liquid Oxygen Enrichment Techniques in the Atacama Large Millimeter/Submillimeter Array Facility at the Chajnantor Plateau (5,050 m).

The Chilean workforce has over 200,000 people that are intermittently exposed to altitudes over 4,000 m. In 2012, the Ministry of Health provided a technical guide for high-altitude workers that included a series of actions to mitigate the effects of hypoxia. Previous studies have shown the positive effect of oxygen enrichment at high altitudes. The Atacama Large Millimeter/submillimeter Array (ALMA) radiotelescope operates at 5,050 m [Array Operations Site (AOS)] and is the only place in the world where pressure swing adsorption (PSA) and liquid oxygen technologies have been installed at a large scale. These technologies reduce the equivalent altitude by increasing oxygen availability. This study aims to perform a retrospective comparison between the use of both technologies during operation in ALMA at 5,050 m. In each condition, variables such as oxygen (O2), temperature, and humidity were continuously recorded in each AOS rooms, and cardiorespiratory variables were registered. In addition, we compared portable O2 by using continuous or demand flow during outdoor activities at very high altitudes. The outcomes showed no differences between production procedures (PSA or liquid oxygen) in regulating oxygen availability at AOS facilities. As a result, big-scale installations have difficulties reaching the appropriate O2 concentration due to leaks in high mobility areas. In addition, the PSA plant requires adequacy and maintenance to operate at a very high altitude. A continuous flow of 2-3 l/min of portable O2 is recommended at 5,050 m.

Assessment of Cardiovascular Risk in Women with Periodontal Diseases According to C-reactive Protein Levels.

Cardiovascular diseases (CVD) are highly prevalent non-communicable diseases worldwide. Periodontitis may act as a non-traditional cardiovascular risk (CVR) factor, linked by a low-grade systemic inflammation mediated by C-reactive protein (CRP). Patients with periodontitis reported higher serum CRP levels; however, a CRP systemic and periodontal correlation in gingival crevicular fluid (GCF) and its CVR impact have been barely studied. We aimed to assess the association between periodontal diseases and CVR in a group of adult women, based on serum high-sensitivity CRP (hs-CRP) levels; and secondly, to determine the association between serum and GCF CRP levels. Gingival crevicular fluid and blood samples were obtained from women with periodontitis, gingivitis, and healthy controls. Serum and GCF CRP were determined by turbidimetric method and Luminex technology, respectively. Data were analyzed and adjusted by CVR factors. All women presented moderate CVR, without an evident association between serum hs-CRP levels and periodontal diseases. While serum hs-CRP concentrations did not significantly differ between groups, patients with gingivitis and periodontitis showed higher CRP levels in GCF, which positively correlated to CRP detection in serum.

Periodontal Treatment Protocol for Decompensated Diabetes Patients.

Background: Decompensated diabetes is associated with a higher prevalence and severity of periodontitis and poorer response to periodontal therapy. It is conceivable that periodontal therapy may cause systemic and local complications in this type of patients. The aim of the present study was to identify and describe the best available evidence for the treatment of periodontitis in decompensated diabetics. Material and methods: An expert committee including participants from different areas gathered to discuss and develop a treatment guideline under the guidance of the Cochrane Associate Center, Faculty of Dentistry, University of Chile. In total, four research questions were prepared. The questions prepared related to decompensated diabetic patients (glycated hemoglobin >8) were, (1) Does the exposure to periodontal treatment increase the risk of infectious or systemic complications? (2) Does the antibiotic treatment or prophylaxis, compared to not giving it, reduce infectious complications? (3) Does the exposure to periodontal treatment, compared to no treatment, reduce the glycated hemoglobin levels (HbA1c)? Last question was related to diabetic patients, (4) Does the exposure to a higher level of HbA1c, compared to stable levels, increase the risk of infectious complications? Based on these questions, a search strategy was developed using MEDLINE and EPISTEMONIKOS. Only systematic reviews were considered. Results: For question 1, the search yielded 12 records in EPISTEMONIKOS and 23 in MEDLINE. None of these studies addressed the question. For question 2, the search yielded 58 records in EPISTEMONIKOS and 11 in MEDLINE. None of these studies addressed the question. For question 3, the search yielded 16 records in EPISTEMONIKOS and 11 in MEDLINE. Thirteen addressed the question. For question 4, the search yielded 7 records in EPISTEMONIKOS and 9 in MEDLINE. One addressed the question. Conclusions: In decompensated diabetic patients, there is lack of scientific information about risk of infectious or systemic complications as a result of periodontal treatment and about the impact of antibiotic treatment or prophylaxis on reduction if infectious complications. A defined HbA1c threshold for dental and periodontal treatment in diabetic patients has yet to be determined. Finally, periodontal treatment does have an impact on HbA1c levels.

Impact of COVID-19 Pandemic on Quality of Life of Type II Diabetes Patients With Periodontitis.

Background: Confinement due to the COVID-19 pandemic has made dental treatments impossible in Chile and many other countries, including diabetic patients with periodontitis. The aim of the present study was to evaluate the impact of periodontal therapy in terms of oral health-related quality of life (OHRQoL) during the COVID-19 pandemic in a cohort of diabetic patients with periodontitis. Material and Methods: Thirty-eight diabetic patients with stage III-IV periodontitis, enrolled for periodontal therapy, were screened. Periodontal clinical parameters including clinical attachment loss (CAL), probing pocket depth (PPD) and bleeding on probing (BOP) as well as glycated hemoglobin (HbA1c) were evaluated at baseline and 3 months follow-up prior the pandemic. The OHRQoL changes by means of Oral Health Impact Profile (OHIP-14) and a self-reported oral health questionnaire were assessed at baseline (prior pandemic) and during the pandemic via telemonitoring. Results: Thirty-one patients received non-surgical periodontal therapy prior to the pandemic. Out of the 31 patients, four died due to COVID-19 resulting in 27 patients available for telemonitoring at the time of the pandemic. Periodontal therapy significantly improved CAL, PPD and BOP (p < 0.05) but not HbA1c (p > 0.05) between baseline and 3 months follow-up pior to the pandemic. Total OHIP-14 scores significantly improved between baseline and the middle of pandemic (intragroup comparison p = 0.00411). In particular, OHIP-14 scores related to the "Physical pain" (intragroup comparison p = 0.04) and "Psychological disability" (intragroup comparison p = 0.00) significantly improved between baseline and the middle of pandemic. Conclusions: In diabetic type II patients with periodontitis periodontal therapy tends to improve the oral health-related quality of life despite the COVID-19 pandemic.

High-Throughput Drug Screening and Multi-Omic Analysis to Guide Individualized Treatment for Multiple Myeloma.

Multiple myeloma (MM) is a genetically heterogeneous malignancy characterized by variable treatment responses. Although numerous drugs have been approved in recent years, the ability to predict treatment response and tailor individual therapy is limited by the absence of robust predictive biomarkers. The goal of this clinical trial was to use ex vivo, high-throughput screening (HTS) of 170 compounds to predict response among patients with relapsed or refractory MM and inform the next treatment decisions. Additionally, we integrated HTS with multi-omic analysis to uncover novel associations between in vitro drug sensitivity and gene expression and mutation profiles. MATERIALS AND METHODS: Twenty-five patients with relapsed or refractory MM underwent a screening bone marrow or soft tissue biopsy. Sixteen patients were found to have sufficient plasma cells for HTS. Targeted next-generation sequencing was performed on plasma cell-free DNA from all patients who underwent HTS. RNA and whole-exome sequencing of bone marrow plasma cells were performed on eight and seven patients, respectively. RESULTS: Results of HTS testing were made available to treating physicians within a median of 5 days from the biopsy. An actionable treatment result was identified in all 16 patients examined. Among the 13 patients who received assay-guided therapy, 92% achieved stable disease or better. The expression of 105 genes and mutations in 12 genes correlated with in vitro cytotoxicity. CONCLUSION: In patients with relapsed or refractory MM, we demonstrate the feasibility of ex vivo drug sensitivity testing on isolated plasma cells from patient bone marrow biopsies or extramedullary plasmacytomas to inform the next line of therapy.

Periodontal disease and its impact on general health in Latin America. Section I: Introduction part I.

A high level of general and oral health are invaluable assets, a factor not always considered a basic human right for their better life quality. The mouth is a critical point of contact with the external environment, which is established when we talk, chew, swallow and when food digestion begins. From a perspective of the human condition, the mouth is crucial for the integration of sound, social appearance of the individual, and is one of the fundamental components of overall health. Therefore, not having an adequate level of oral health affects self-esteem, quality of life and people's general well-being.

Effect of periodontal treatment in patients with periodontitis and diabetes: systematic review and meta-analysis.

OBJECTIVE: The evidence is inconclusive regarding the effect of periodontal treatment on glycemic control and systemic inflammation in patients with type 2 diabetes (T2D) and periodontitis. To evaluate the effect of scaling and root planing (SRP) on the metabolic control and systemic inflammation of patients with type 2 diabetes (T2D). METHODOLOGY: A literature search was conducted using the MEDLINE database via PubMed and the Cochrane Central Register of Controlled Trials, from their oldest records up to July 2018. Only randomized clinical trials (RCT) were considered eligible for evaluating the effect of periodontal treatment on markers of metabolic control [glycated hemoglobin (HbA1C)] and systemic inflammation [C-reactive protein (CRP)] in patients with T2D. The quality of the studies was evaluated using the Cochrane Collaboration risk assessment tool. Meta-analyses were performed for HbA1c and CRP using random effects models. The size of the overall intervention effect was estimated by calculating the weighted average of the differences in means (DM) between the groups in each study. Heterogeneity was assessed using the Q-statistic method (x2 and I²). The level of significance was established at p<0.05. RESULTS: Nine RCT were included. SRP was effective in reducing HbA1c [DM=0.56 (0.36-0.75); p<0.01] and CRP [DM=1.89 (1.70-2.08); p<0.01]. No heterogeneity was detected (I2=0%, p>0.05). CONCLUSIONS: SRP has an impact on metabolic control and reduction of systemic inflammation of patients with T2D.

Breast cancer detection in Mexico City during 2017. / Detección del cáncer de mama en la Ciudad de México durante 2017.

BACKGROUND: Breast cancer is the leading cause of death of women in Mexico; its detection is among the priorities of Mexico City's (CDMX) Southern Local Office from the Instituto Mexicano del Seguro Social (IMSS: Mexican Institute for Social Security). OBJECTIVE: To describe the incidence and mortality related to breast cancer detection in the CDMX's Southern Local Office units from IMSS in 2017. MATERIAL AND METHODS: Databases from the Coordination of Prevention and Health Care (CPAS), Information and Strategic Analysis (CIAE) and the Breast Clinic (UDDC Mama) were analyzed. Among data, it was included age, study (mastography, ultrasound and biopsy), and histological type, incidence and mortality. For statistical analysis it was used Student's t, and Spearman correlation (p < 0.05). RESULTS: In a population of 589,683 women (40-69 years), 97,779 mastographs were performed. Out of these, there were 94,883 normal (BI-RADS 1) and 1933 suspicious (BIRADS 3-5). In 436 biopsies, infiltrating ductal carcinoma was the most frequent. The incidence rate was 39.3/100,000 and the mortality rate was 3.54/100,000 inhabitants (in 2015 and 2016 it was 6.84 and 7.02/100,000, respectively). CONCLUSIONS: An increase in the incidence and a decrease in breast cancer mortality has been observed, which is related to improvements in screening programs in 2017. It is important to maintain and optimize screening programs.

INTRODUCCIÓN: El cáncer de mama es la principal causa de muerte de mujeres en México; su detección se ubica entre las prioridades de la Delegación Sur de la Ciudad de México del Instituto Mexicano del Seguro Social (IMSS). OBJETIVO: Describir la incidencia y la mortalidad relacionadas con la detección del cáncer de mama en las unidades de la Delegación Sur de la Ciudad de México del IMSS en 2017. MATERIAL Y MÉTODOS: Se analizaron las bases de datos de las Coordinaciones de Prevención y Atención a la Salud (CPAS), de Información y Análisis Estratégico (CIAE) y de la Clínica de Mama (UDDC Mama). Entre los datos se incluyó edad, estudio (mastografía, ultrasonido y biopsia) y tipo histológico, incidencia y mortalidad. Para el análisis estadístico se empleó t de Student y correlación de Spearman (p ≤ 0.05). RESULTADOS: En una población de 589 683 mujeres (40-69 años), se realizaron 97 779 mastografías. De estas hubo 94 883 normales (BIRADS 1) y 1933 sospechosas (BIRADS 3-5). En 436 biopsias, el carcinoma ductal infiltrante fue el más frecuente. La tasa de incidencia fue 39.3/100 000 y de mortalidad de 3.54/100 000 habitantes (en 2015 y 2016 fue de 6.84 y 7.02/100 000, respectivamente). CONCLUSIONES: Se ha observado un incremento en la incidencia y disminución de mortalidad por cáncer de mama, el cual está relacionado con mejoras en programas de detección en 2017. Es importante mantener y optimizar los programas de detección.

[Lidocaine with epinephrine effect on arterial tension of children]. / Efecto de la lidocaína con epinefrina en la tensión arterial de una población infantil.

OBJECTIVE: to determine the effect of the epinephrine-lidocaine anaesthetic solutions on blood pressure in healthy children subjected to short dentistry procedures. METHODS: we performed a prospective, observational and analytical study in 39 children with 7 and 8 years of age, who were subjected to dentistry treatment of short duration in a dentistry service. The blood pressure was measured in three times: previous to the infiltration of lidocaine to 2 % with epinephrine; 10 minutes later; at the end of procedure. RESULTS: the systolic blood pressure, like diastolic and the average increased after 10 minutes of the infiltration with the anesthetic-vasoconstrictor solution, but this difference was not significant (p = 0.39, 0.14 and 0.40). We observed an increase of the systolic (6.0 mm Hg, 95 % CI = 4.6-7.5, F = 14.0, p = 0.0001), diastolic (9.9 mm Hg, 95 % CI = 7.3-12.5; F = 26.0, p = 0.0001) and average arterial tension (7.3 mm Hg, 95 % IC = 5.8-8.8; F = 23, p = 0.0001) to the 10 minutes after the treatment. CONCLUSIONS: the use of the epinephrine-lidocaine anaesthetic solutions does not have significant effect on the blood pressure of children subjected to short dentistry procedures.

Programa de atención de vacunación contra el COVID-19 al personal del hospital de Huaycán / COVID-19 vaccination program for Huaycán hospital personnel / Programa de vacinação contra a COVID-19 para a equipe do hospital de Huaycán

A la fecha las vacunas para prevenir el COVID-19, representan la mejor esperanza para combatir el virus, además que éstas constituyeron un reto en la cadena de participación de reparto y distribución para las autoridades estatales en Perú, con respecto a priorizar dentro de la ciudadanía la adecuada administración por parte de quienes participaron en el proceso de vacunación. Objetivo. Analizar la gestión de la distribución y aplicación de la vacuna contra el COVID-19 en el Hospital de Huaycán. Materiales y Métodos. Se diseñó un estudio no experimental, de nivel aplicativo de enfoque cuantitativo, tipo de análisis descriptivo de corte transversal. La población estuvo conformada por 700 profesionales que laboran en dicho hospital. Las técnicas que fueron utilizadas fue la entrevista y la encuesta usando como instrumento un formulario de tipo cuestionario. Resultados. En cuanto a las medidas de prevención del virus en el personal de salud se realizaban pruebas diagnósticas a los trabajadores (pruebas rápidas y PCR) para identificar los casos sospechosos a un total de 2590 trabajadores, de los cuales 2372 se les realizó pruebas rápidas y 218 hisopados. En cuanto al nivel de ejecución de la vacunación se pudo determinar que totalidad de los trabajadores del Hospital de Huaycán, no alcanzaron a estar vacunados en el tiempo de aplicación de vacuna. Conclusiones. La gestión de la distribución y aplicación de la vacuna contra el COVID-19 en el Hospital de Huaycán revela una serie de aspectos tanto positivos como preocupantes. Si bien se observan indicadores de gestión adecuados en la administración de la vacuna, es evidente que la cobertura no ha alcanzado el 100%, lo cual implica retos en términos de alcance y eficacia de la inmunización en la población hospitalaria.

To date, vaccines to prevent COVID-19 represent the best hope for combating the virus, and they represent a challenge in the chain of distribution and distribution participation for state authorities in Peru, with respect to prioritizing the adequate administration by those who participated in the vaccination process among the citizens. Objective. To analyze the management of the distribution and application of the vaccine against COVID-19 in the Huaycán Hospital. Materials and Methods. A non-experimental study was designed, with a quantitative approach, descriptive cross-sectional analysis. The population consisted of 700 professionals working in the hospital. The techniques used were the interview and the survey using a questionnaire-type form as an instrument. Results. Regarding virus prevention measures in health personnel, diagnostic tests were performed on workers (rapid tests and PCR) to identify suspected cases in a total of 2,590 workers, of whom 2,372 underwent rapid tests and 218 swabs. As for the level of implementation of vaccination, it was determined that all the workers of the Hospital de Huaycán were not vaccinated at the time of vaccine application. Conclusions. The management of the distribution and application of the vaccine against COVID-19 in the Huaycán Hospital reveals a series of both positive and worrying aspects. Although adequate management indicators are observed in the administration of the vaccine, it is evident that coverage has not reached 100%, which implies challenges in terms of scope and efficacy of immunization in the hospital population.

Até o momento, as vacinas para prevenir a COVID-19 representam a melhor esperança para o combate ao vírus e têm representado um desafio na cadeia de participação na distribuição e distribuição para as autoridades estatais no Peru, com relação à priorização da administração adequada por parte dos envolvidos no processo de vacinação entre os cidadãos. Objetivo. Analisar a gestão da distribuição e aplicação da vacina contra a COVID-19 no Hospital Huaycán. Materiais e métodos. Foi projetado um estudo não experimental, com uma análise quantitativa, descritiva, transversal e transversal. A população foi composta por 700 profissionais que trabalham no hospital. As técnicas utilizadas foram entrevistas e pesquisas usando um formulário do tipo questionário como instrumento. Resultados. Em termos de medidas de prevenção do vírus entre o pessoal de saúde, foram realizados testes diagnósticos nos trabalhadores (testes rápidos e PCR) para identificar casos suspeitos em um total de 2.590 trabalhadores, dos quais 2.372 foram submetidos a testes rápidos e 218 a swabs. Em termos do nível de implementação da vacinação, foi determinado que todos os trabalhadores do Hospital Huaycán não foram vacinados dentro do período de vacinação. Conclusões. O gerenciamento da distribuição e aplicação da vacina contra a COVID-19 no Hospital Huaycán revela uma série de aspectos positivos e preocupantes. Embora sejam observados indicadores de gestão adequados na administração da vacina, é evidente que a cobertura não atingiu 100%, o que implica desafios em termos de alcance e eficácia da imunização na população do hospital.