Integrative oncology: Addressing the global challenges of cancer prevention and treatment.

The increase in cancer incidence and mortality is challenging current cancer care delivery globally, disproportionally affecting low- and middle-income countries (LMICs) when it comes to receiving evidence-based cancer prevention, treatment, and palliative and survivorship care. Patients in LMICs often rely on traditional, complementary, and integrative medicine (TCIM) that is more familiar, less costly, and widely available. However, spheres of influence and tensions between conventional medicine and TCIM can further disrupt efforts in evidence-based cancer care. Integrative oncology provides a framework to research and integrate safe, effective TCIM alongside conventional cancer treatment and can help bridge health care gaps in delivering evidence-informed, patient-centered care. This growing field uses lifestyle modifications, mind and body therapies (eg, acupuncture, massage, meditation, and yoga), and natural products to improve symptom management and quality of life among patients with cancer. On the basis of this review of the global challenges of cancer control and the current status of integrative oncology, the authors recommend: 1) educating and integrating TCIM providers into the cancer control workforce to promote risk reduction and culturally salient healthy life styles; 2) developing and testing TCIM interventions to address cancer symptoms or treatment-related adverse effects (eg, pain, insomnia, fatigue); and 3) disseminating and implementing evidence-based TCIM interventions as part of comprehensive palliative and survivorship care so patients from all cultures can live with or beyond cancer with respect, dignity, and vitality. With conventional medicine and TCIM united under a cohesive framework, integrative oncology may provide citizens of the world with access to safe, effective, evidence-informed, and culturally sensitive cancer care.

Revisiting Biginelli-like reactions: solvent effects, mechanisms, biological applications and correction of several literature reports.

This study critically reevaluates reported Biginelli-like reactions using a Kamlet-Abboud-Taft-based solvent effect model. Surprisingly, structural misassignments were discovered in certain multicomponent reactions, leading to the identification of pseudo three-component derivatives instead of the expected MCR adducts. Attempts to replicate literature conditions failed, prompting reconsideration of the described MCRs and proposed mechanisms. Electrospray ionization (tandem) mass spectrometry, NMR, melting points, elemental analyses and single-crystal X-ray analysis exposed inaccuracies in reported MCRs and allowed for the proposition of a complete catalytic cycle. Biological investigations using both pure and "contaminated" derivatives revealed distinctive features in assessed bioassays. A new cellular action mechanism was unveiled for a one obtained pseudo three-component adduct, suggesting similarity with the known dihydropyrimidinone Monastrol as Eg5 inhibitors, disrupting mitosis by forming monoastral mitotic spindles. Docking studies and RMSD analyses supported this hypothesis. The findings described herein underscore the necessity for a critical reexamination and potential corrections of structural assignments in several reports. This work emphasizes the significance of rigorous characterization and critical evaluation in synthetic chemistry, urging a careful reassessment of reported synthesis and biological activities associated with these compounds.

Delivery of hereditary cancer genetics services to patients newly diagnosed with ovarian and endometrial cancers at three gynecologic oncology clinics in the USA, Brazil, and Mexico.

OBJECTIVE: Three gynecologic oncology clinics located in the USA, Brazil, and Mexico collaborated to evaluate their delivery of hereditary cancer genetics services. This descriptive retrospective review study aimed to establish baseline rates and timeliness of guideline-recommended genetics service delivery to patients with ovarian, fallopian tube, primary peritoneal (ovarian), and endometrial cancers at each clinic. METHODS: Patients who were newly diagnosed with ovarian and endometrial cancers between September 1, 2018 and December 31, 2020 were identified from the medical records of the clinics. Genetics service delivery metrics included the rates of mismatch repair deficiency tumor testing for patients with endometrial cancer (microsatellite instability/immunohistochemistry, MSI/IHC), referral to genetics services for patients with ovarian cancer, completed genetics consultations, and germline genetic testing for patients with ovarian and endometrial cancers. Timeliness was calculated as the average number of days between diagnosis and the relevant delivery metric. Descriptive statistics were used to analyze data. RESULTS: In total, 1195 patients (596 with ovarian cancer, 599 with endometrial cancer) were included in the analysis, and rates of genetics service delivery varied by clinic. For patients with ovarian cancer, referral rates ranged by clinic from 32.6% to 89.5%; 30.4-65.1% of patients completed genetics consultation and 32.6-68.7% completed genetic testing. The timeliness to genetic testing for patients with ovarian cancer ranged by clinic from 107 to 595 days. A smaller proportion of patients with endometrial cancer completed MSI/IHC testing (10.0-69.2%), with the average time to MSI/IHC ranging from 15 to 282 days. Rates of genetics consultation among patients with endometrial cancer ranged by clinic from 10.8% to 26.0% and 12.5-16.6% completed genetic testing. CONCLUSIONS: All clinics successfully established baseline rates and timeliness of delivering hereditary cancer genetics services to patients with ovarian and endometrial cancers. Lower rates of delivering genetics services to patients with endometrial cancer warrant additional research and quality improvement efforts.

Cyrene: a very reactive bio-based chiral ketone in diastereoselective Passerini reactions.

Cyrene, a green bioderived solvent from waste cellulose, was applied to the synthesis of novel α-acyloxyamide derivatives through a Passerini-3CR with carboxylic acids and isocyanides with good yields and diastereoselectivities under mild conditions. Cyrene showed exceptionally high reactivity and the degree of diastereoselection was dependent mostly on the isocyanide. DFT calculations as well as the experimental findings indicated that both kinetic and thermodynamic effects might explain the results.

Dental and periodontal dimensions stability after esthetic clinical crown lengthening surgery: a 12-month clinical study.

OBJECTIVES: To evaluate the stability of periodontal tissues 3 (T3), 6 (T6), and 12 (T12) months after esthetic crown lengthening (ACL) and the possible correlations between changes in those structures. MATERIALS AND METHODS: Twenty individuals were evaluated through clinical assessment, photography, and tomography. Measurements included gingival margin (GM), clinical crown length (CCL), interdental papilla height (PH) and width (PW), gingival thickness (GT), bone thickness (BT), probing depth (PD), distance between alveolar crest and GM, distance between alveolar crest and cementoenamel junction. Nonparametric and correlation statistics were performed (p < 0.05). RESULTS: CCL at T0 was 7.42 ± 0.70 mm and increased to 9.48 ± 0.49 mm immediately after ACL, but it decreased to 8.93 ± 0.65 mm at T12. PD decreased 0.60 mm from T0 to T6, and it increased 0.39 mm from T6 to T12. BT decreased 0.20 mm, while GT increased 0.29 mm from T0 to T12. Both PW and PH showed enlargement in T12. A positive moderate correlation was found between CCL/T0 and CCL/T12, GT/T0 and AC-GM/T12, BT/T0 and GT/T12. A few negative moderate correlations were PD/T0 and CCL/T12, PD/T0 and PH/T0, PD/T0 and BT/T12. CONCLUSIONS: ACL procedure was effective. Although some rebound occurred, that was not clinically important. PD tended to reestablish its original length, partially due to a migration of GM during the healing period. Besides, a thickening of supracrestal soft tissues was observed. CLINICAL RELEVANCE: The present study centers on the factors influencing the stability of periodontal tissues after esthetic crown lengthening, underscoring the procedure's influence on esthetics and biology and the need for careful treatment planning.

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines.

The imidazo[1,2-a]pyridine moiety is present in drugs with several biological activities. The most direct way of obtaining this nucleus is the Groebke-Blackburn-Bienaymé three-component reaction (GBB-3CR) between aminopyridines, aldehydes, and isocyanides under both Lewis and Brønsted acid catalysis. However, several catalysts for this reaction have major drawbacks such as being expensive, extremely dangerous, strong oxidizing, and even explosive. In this scenario, heteropolyacids emerge as greener and safer alternatives due to their very strong Brønsted acidity. In particular, phosphotungstic acid (HPW) is an economical and green attractive catalyst for being cheap, non-toxic, and is known for its chemical and thermal stability. Herein, we report a straightforward approach to the GBB-3CR using HPW as catalyst in ethanol under microwave (µw) heating. This convenient environmentally benign methodology is broad in scope, provides the heterobicyclic products in high yields (up to 99%), with a low catalyst loading (2 mol %) in only 30 minutes, and allows the successful use of aliphatic aldehydes, substrates not so frequently explored with most usual catalysts for this reaction. Furthermore, the aforementioned advantages make this methodology very attractive and superior to the existing ones.

Inequalities in the burden of non-communicable diseases across European countries: a systematic analysis of the Global Burden of Disease 2019 study.

BACKGROUND: Although overall health status in the last decades improved, health inequalities due to non-communicable diseases (NCDs) persist between and within European countries. There is a lack of studies giving insights into health inequalities related to NCDs in the European Economic Area (EEA) countries. Therefore, the aim of the present study was to quantify health inequalities in age-standardized disability adjusted life years (DALY) rates for NCDs overall and 12 specific NCDs across 30 EEA countries between 1990 and 2019. Also, this study aimed to determine trends in health inequalities and to identify those NCDs where the inequalities were the highest. METHODS: DALY rate ratios were calculated to determine and compare inequalities between the 30 EEA countries, by sex, and across time. Annual rate of change was used to determine the differences in DALY rate between 1990 and 2019 for males and females. The Gini Coefficient (GC) was used to measure the DALY rate inequalities across countries, and the Slope Index of Inequality (SII) to estimate the average absolute difference in DALY rate across countries. RESULTS: Between 1990 and 2019, there was an overall declining trend in DALY rate, with larger declines among females compared to males. Among EEA countries, in 2019 the highest NCD DALY rate for both sexes were observed for Bulgaria. For the whole period, the highest DALY rate ratios were identified for digestive diseases, diabetes and kidney diseases, substance use disorders, cardiovascular diseases (CVD), and chronic respiratory diseases - representing the highest inequality between countries. In 2019, the highest DALY rate ratio was found between Bulgaria and Iceland for males. GC and SII indicated that the highest inequalities were due to CVD for most of the study period - however, overall levels of inequality were low. CONCLUSIONS: The inequality in level 1 NCDs DALYs rate is relatively low among all the countries. CVDs, digestive diseases, diabetes and kidney diseases, substance use disorders, and chronic respiratory diseases are the NCDs that exhibit higher levels of inequality across countries in the EEA. This might be mitigated by applying tailored preventive measures and enabling healthcare access.

Does sentinel node mapping impact morbidity and quality of life in endometrial cancer?

OBJECTIVES: To evaluate the prevalence of post-operative complications and quality of life (QoL) related to sentinel lymph node (SLN) biopsy vs systematic lymphadenectomy in endometrial cancer. METHODS: A prospective cohort included women with early-stage endometrial carcinoma who underwent lymph node staging, grouped as follows: SLN group (sentinel lymph node only) and SLN+LND group (sentinel lymph node biopsy with addition of systematic lymphadenectomy). The patients had at least 12 months of follow-up, and QoL was assessed by European Organization for Research and Treatment of Cervical Cancer Quality of Life Questionnaire 30 (EORTC-QLQ-C30) and EORTC-QLQ-Cx24. Lymphedema was also assessed by clinical evaluation and perimetry. RESULTS: 152 patients were included: 113 (74.3%) in the SLN group and 39 (25.7%) in the SLN+LND group. Intra-operative surgical complications occurred in 2 (1.3%) cases, and all belonged to SLN+LND group. Patients undergoing SLN+LND had higher overall complication rates than those undergoing SLN alone (33.3% vs 14.2%; p=0.011), even after adjusting for confound factors (OR=3.45, 95% CI 1.40 to 8.47; p=0.007). The SLN+LND group had longer surgical time (p=0.001) and need for admission to the intensive care unit (p=0.001). Moreover, the incidence of lymphocele was found in eight cases in the SLN+LND group (0 vs 20.5%; p<0.001). There were no differences in lymphedema rate after clinical evaluation and perimetry. However, the lymphedema score was highest when lymphedema was reported by clinical examination at 6 months (30.1 vs 7.8; p<0.001) and at 12 months (36.3 vs 6.0; p<0.001). Regarding the overall assessment of QoL, there was no difference between groups at 12 months of follow-up. CONCLUSIONS: There was a higher overall rate of complications for the group undergoing systematic lymphadenectomy, as well as higher rates of lymphocele and lymphedema according to the symptom score. No difference was found in overall QoL between SLN and SLN+LND groups.

CYP broth: a tool for Yersinia pestis isolation in ancient culture collections and field samples.

We developed a simple new selective LB-based medium, named CYP broth, suitable for recovering long-term stored Y. pestis subcultures and for isolation of Y. pestis strains from field-caught samples for the Plague surveillance. It aimed to inhibit the growth contaminating microorganisms and enrich Y. pestis growth through iron supplementation. The performance of CYP broth on microbial growth from different gram-negative and gram-positive strains from American Type Culture Collection (ATCC®) and other clinical isolates, field-caught rodent samples, and more importantly, on several vials of ancient Y. pestis subcultures was evaluated. Additionally, other pathogenic Yersinia species such as Y. pseudotuberculosis and Y. enterocolitica were also successfully isolated with CYP broth. Selectivity tests and bacterial growth performance on CYP broth (LB broth supplemented with Cefsulodine, Irgasan, Novobiocin, nystatin and ferrioxamine E) were evaluated in comparison with LB broth without additive; LB broth/CIN, LB broth/nystatin and with traditional agar media including LB agar without additive, and LB agar and Cefsulodin-Irgasan-Novobiocin Agar (CIN agar) supplemented with 50 µg/mL of nystatin. Of note, the CYP broth had a recovery twofold higher than those of the CIN supplemented media or other regular media. Additionally, selectivity tests and bacterial growth performance were also evaluated on CYP broth in the absence of ferrioxamine E. The cultures were incubated at 28 °C and visually inspected for microbiological growth analysis and O.D.625 nm measurement between 0 and 120 h. The presence and purity of Y. pestis growth were confirmed by bacteriophage and multiplex PCR tests. Altogether, CYP broth provides an enhanced growth of Y. pestis at 28 °C, while inhibiting contaminant microorganisms. The media is a simple, but powerful tool to improve the reactivation and decontamination of ancient Y. pestis culture collections and for the isolation of Y. pestis strains for the Plague surveillance from various backgrounds. KEY POINTS: • The newly described CYP broth improves the recuperation of ancient/contaminated Yersinia pestis culture collections • CYP broth was also efficient in reducing environmental contamination in field-capture samples, improving Y. pestis isolation • CYP broth can also be used for the isolation of Y. enterocolitica and Y. pseudotuberculosis.

How Does Neural Network Model Capacity Affect Photovoltaic Power Prediction? A Study Case.

The use of models capable of forecasting the production of photovoltaic (PV) energy is essential to guarantee the best possible integration of this energy source into traditional distribution grids. Long Short-Term Memory networks (LSTMs) are commonly used for this purpose, but their use may not be the better option due to their great computational complexity and slower inference and training time. Thus, in this work, we seek to evaluate the use of neural networks MLPs (Multilayer Perceptron), Recurrent Neural Networks (RNNs), and LSTMs, for the forecast of 5 min of photovoltaic energy production. Each iteration of the predictions uses the last 120 min of data collected from the PV system (power, irradiation, and PV cell temperature), measured from 2019 to mid-2022 in Maceió (Brazil). In addition, Bayesian hyperparameters optimization was used to obtain the best of each model and compare them on an equal footing. Results showed that the MLP performs satisfactorily, requiring much less time to train and forecast, indicating that they can be a better option when dealing with a very short-term forecast in specific contexts, for example, in systems with little computational resources.

Rational Design and Multicomponent Synthesis of Lipid-Peptoid Nanocomposites towards a Customized Drug Delivery System Assembly.

Nanotechnology has assumed a significant role over the last decade in the development of various technologies applied to health sciences. This becomes even more evident with its application in controlled drug delivery systems. In this context, peptoids are a promising class of compounds for application as nanocarriers in drug delivery systems. These compounds can be obtained efficiently and with highly functionalized structural diversity via the Ugi 4-component reaction (U-4CR). Herein, we report the design of the process control strategy for the future development of lipid-peptoid-based customized drug delivery system assemblies. Over 20 lipid-peptoid nanocomposites were synthesized via the U-4CR in good to excellent yields. These products were successfully submitted to the nanoparticle formation by the emulsification-evaporation process from lipophilic solution and analyzed via Dynamic Light Scattering (DLS). Several molecules generated nanoparticles with a size ≤200 nm, making them good candidates for drug delivery systems, such as in cancer treatment.

Open Versus Minimally Invasive Radical Hysterectomy in Cervical Cancer: The CIRCOL Group Study.

PURPOSE: To analyze the survival outcomes of patients in a Brazilian cohort who underwent minimally invasive surgery (MIS) compared with open surgery for early stage cervical cancer. METHODS: A multicenter database was constructed, registering 1280 cervical cancer patients who had undergone radical hysterectomy from 2000 to 2019. For the final analysis, we included cases with a tumor ≤ 4 cm (stages Ia2 to Ib2, FIGO 2018) that underwent surgery from January 2007 to December 2017. Propensity score matching was also performed. RESULTS: A total of 776 cases were ultimately analyzed, 526 of which were included in the propensity score matching analysis (open, n = 263; MIS, n = 263). There were 52 recurrences (9.9%), 28 (10.6%) with MIS and 24 (9.1%) with open surgery (p = 0.55); and 34 deaths were recorded, 13 (4.9%) and 21 (8.0%), respectively (p = 0.15). We noted a 3-year disease-free survival (DFS) rate of 88.2% and 90.3% for those who received MIS and open surgery, respectively (HR 1.32; 95% CI: 0.76-2.29; p = 0.31) and a 5-year overall survival (OS) rate of 91.8% and 91.1%, respectively (HR 0.80; 95% CI: 0.40-1.61; p = 0.53). There was no difference in 3-year DFS rates between open surgery and MIS for tumors ≤ 2 cm (95.7% vs. 90.8%; p = 0.16) or > 2 cm (83.9% vs. 85.4%; p = 0.77). Also, the 5-year OS between open surgery and MIS did not differ for tumors ≤ 2 cm (93.1% vs. 93.6%; p = 0.82) or > 2 cm (88.9% vs. 89.8%; p = 0.35). CONCLUSIONS: Survival outcomes were similar between minimally invasive and open radical hysterectomy in this large retrospective multicenter cohort.

Cancer risk-reducing surgery: Brazilian society of surgical oncology guideline part 1 (gynecology and breast).

BACKGROUND: Risk-reducing operations are an important part of the management of hereditary predisposition to cancer. In selected cases, they can considerably reduce the morbidity and mortality associated with cancer in this population. OBJECTIVES: The Brazilian Society of Surgical Oncology (BSSO) developed this guideline to establish national benchmarks for cancer risk-reducing operations. METHODS: The guideline was prepared from May to December 2021 by a multidisciplinary team of experts to discuss the surgical management of cancer predisposition syndromes. Fourteen questions were defined and assigned to expert groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including risk-reduction bilateral salpingo-oophorectomy, hysterectomy, and mastectomy, major agreement was achieved by the participants, always using accessible alternatives. CONCLUSION: This and its accompanying article represent the first guideline in cancer risk reduction surgery developed by the BSSO, and it should serve as an important reference for the management of families with cancer predisposition.

Cancer risk-reducing surgery: Brazilian Society of Surgical Oncology Guideline Part 2 (Gastrointestinal and thyroid).

BACKGROUND: Risk-reducing operations are an important part of the management of hereditary predisposition to cancer. In selected cases, they can considerably reduce the morbidity and mortality associated with cancer in this population. OBJECTIVES: The Brazilian Society of Surgical Oncology (BSSO) developed this guideline to establish national benchmarks for cancer risk-reducing operations. METHODS: The guideline was prepared from May to December 2021 by a multidisciplinary team of experts to discuss the surgical management of cancer predisposition syndromes. Eleven questions were defined and assigned to expert groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including risk-reducing colectomy, gastrectomy, and thyroidectomy, a major agreement was achieved by the participants, always using accessible alternatives. CONCLUSION: This and its accompanying article represent the first guideline in cancer risk reduction surgery developed by the BSSO and it should serve as an important reference for the management of families with cancer predisposition.

Brazilian Society of Surgical Oncology consensus on fertility-sparing surgery for cervical cancer.

OBJECTIVE: Several controversies remain on conservative management of cervical cancer. Our aim was to develop a consensus recommendation on important and novel topics of fertility-sparing treatment of cervical cancer. METHODS: The consensus was sponsored by the Brazilian Society of Surgical Oncology (BSSO) from March 2020 to September 2020 and included a multidisciplinary team of 55 specialists. A total of 21 questions were addressed and they were assigned to specialists' groups that reviewed the literature and drafted preliminary recommendations. Further, the coordinators evaluated the recommendations that were classified by the level of evidence, and finally, they were voted by all participants. RESULTS: The questions included controversial topics on tumor assessment, surgical treatment, and surveillance in conservative management of cervical cancer. The two topics with lower agreement rates were the role of minimally invasive approach in radical trachelectomy and parametrial preservation. Additionally, only three recommendations had <90% of agreement (fertility preservation in Stage Ib2, anti-stenosis device, and uterine transposition). CONCLUSIONS: As very few clinical trials have been developed in surgery for cervical cancer, most recommendations were supported by low levels of evidence. We addressed important and novel topics in conservative management of cervical cancer and our study may contribute to literature.

Prognostic role of hydronephrosis in the treatment of patients with locally advanced cervical cancer: a retrospective cohort.

BACKGROUND: Obstructive uropathy is present in almost 50% of patients with advanced cervical cancer and is associated with worse outcomes. OBJECTIVE: To estimate the prognostic role of hydronephrosis and the impact of ureteral obstruction resolution in patients with locally advanced cervical cancer undergoing treatment. METHODS: A retrospective cohort study was conducted of patients with International Federation of Gynecology and Obstetrics 2018 stage IIIB to IVA treated in a tertiary oncologic referral center in Brazil between January 2009 and June 2018. Three different groups were evaluated: (I) without hydronephrosis, (II) with hydronephrosis and urinary diversion, and (III) with hydronephrosis but no urinary diversion. Kaplan-Meier curves and log-rank tests estimated overall survival and progression-free survival based on the presence of hydronephrosis and urinary diversion. Clinicopathological variables were evaluated using univariate and multivariate Cox proportional hazard regression model for overall survival and progression-free survival. RESULTS: A total of 151 patients were evaluated: group I - 62 (41.1%); II - 44 (29.1%), and III - 45 (29.8%). Stage, histological type or grade, tumor size, parametrial or lymph node involvement were not statistically different between groups. Group I had more favorable overall survival than groups II (p<0.003) and III (p<0.02); however, no difference was noted between groups II and III. Progression-free survival was similar between groups (log-rank test p=0.95). Univariate analysis revealed hydronephrosis (p=0.002) and concurrent chemoradiotherapy (p<0.001) as a prognostic factor for worse overall survival; while tumor size (p=0.023), pelvic lymphadenopathy (p=0.015), and histological type (p=0.03) were associated with worse progression-free survival. On multivariate analysis, hydronephrosis remained as an independently associated factor with worse overall survival (HR=2.06; 95% CI 1.12 to 3.79, p=0.02). CONCLUSION: Patients with locally advanced cervical cancer with hydronephrosis had lower overall survival even after controlling for potential confounding factors, but no difference in progression-free survival. Urinary diversion showed no impact on overall survival or progression-free survival.

Sentinel lymph node mapping versus sentinel lymph node mapping with systematic lymphadenectomy in endometrial cancer: an open-label, non-inferiority, randomized trial (ALICE trial).

BACKGROUND: Growing evidence suggest that sentinel lymph node (SLN) biopsy in endometrial cancer accurately detects lymph node metastasis. However, prospective randomized trials addressing the oncological outcomes of SLN biopsy in endometrial cancer without lymphadenectomy are lacking. PRIMARY OBJECTIVES: The present study aims to confirm that SLN biopsy without systematic node dissection does not negatively impact oncological outcomes. STUDY HYPOTHESIS: We hypothesized that there is no survival benefit in adding systematic lymphadenectomy to sentinel node mapping for endometrial cancer staging. Additionally, we aim to evaluate morbidity and impact in quality of life (QoL) after forgoing systematic lymphadenectomy. TRIAL DESIGN: This is a collaborative, multicenter, open-label, non-inferiority, randomized trial. After total hysterectomy, bilateral salpingo-oophorectomy and SLN biopsy, patients will be randomized (1:1) into: (a) no further lymph node dissection or (b) systematic pelvic and para-aortic lymphadenectomy. MAJOR INCLUSION AND EXCLUSION CRITERIA: Inclusion criteria are patients with high-grade histologies (endometrioid G3, serous, clear cell, and carcinosarcoma), endometrioid G1 or G2 with imaging concerning for myometrial invasion of ≥50% or cervical invasion, clinically suitable to undergo systematic lymphadenectomy. PRIMARY ENDPOINTS: The primary objective is to compare 3-year disease-free survival and the secondary objectives are 5-year overall survival, morbidity, incidence of lower limb lymphedema, and QoL after SLN mapping ± systematic lymphadenectomy in high-intermediate and high-risk endometrial cancer. SAMPLE SIZE: 178 participants will be randomized in this study with an estimated date for completing accrual of December 2024 and presenting results in 2027. TRIAL REGISTRATION NUMBER: NCT03366051.

Survival rate and peri-implant evaluation of immediately loaded dental implants in individuals with type 2 diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the survival rate, success rate, and peri-implant biological changes of immediately loaded dental implants (ILs) placed in type 2 diabetic patients (DM2). MATERIALS AND METHODS: The present study was registered on PROSPERO and followed the PRISMA checklist. The search was performed by the first reviewer in January 2021. The electronic databases used were MEDLINE via PubMed, Cochrane, BVS, Web of Science, Scopus, LIVIVO, and gray literature. The risk of bias analysis was performed using an instrument from the Joanna Briggs Institute. RESULTS: A total of 3566 titles and abstracts were obtained. The qualitative synthesis included 7 studies, while the quantitative synthesis included 5 studies. The meta-analysis of IL in individuals with DM2 compared to nondiabetic individuals showed no significant difference among the groups regarding the survival rate of dental implants (RR = 1.00, 95% CI 0.96-1.04; p = 0.91; I2 = 0%), even if the patient had poor glycemic control (RR = 1.08, 95% CI 0.87-1.33; p = 0.48; I2 = 70%). Meta-analysis of marginal bone loss in IL compared to conventional loading in DM2 patients also showed no significant difference (mean difference = - 0.08, 95% CI - 0.25-0.08; p = 0.33; I2 = 83%). CONCLUSIONS: Type 2 diabetes mellitus does not seem to be a risk factor for immediately loaded implants if the glycemic level is controlled, the oral hygiene is satisfactory, and the technical steps are strictly followed. Clinical relevance Rehabilitation in diabetic individuals is more common due to the highest prevalence of edentulism in this population. It is essential to establish appropriate protocols for loading dental implants.

Whole-exome sequencing of non-BRCA1/BRCA2 mutation carrier cases at high-risk for hereditary breast/ovarian cancer.

The current study aimed to identify new breast and/or ovarian cancer predisposition genes. For that, whole-exome sequencing (WES) was performed in the germline DNA of 52 non-BRCA1/BRCA2/TP53 mutation carrier women at high-risk for hereditary breast and ovarian cancer (HBOC). All variants were classified using information from population and disease specific databases, in silico prediction tools and the American College of Medical Genetics and Genomics (ACMG) criteria. Loss of heterozygosity (LOH) of tumor samples and segregation analyses were performed whenever possible. The variants identified were investigated in a second, independent cohort of 17 BC cases. Pathogenic/Likely Pathogenic variants were identified in known cancer genes such as CHEK2, MUTYH, PMS2, and RAD51C. Rare and potentially pathogenic variants were identified in DNA repair genes (FAN1, POLQ, and RAD54L) and other cancer-related genes such as DROSHA and SLC34A2. Interestingly, the variant c.149T>G in the FAN1 gene was identified in two unrelated families, and exhibited LOH in the tumor tissue of one of them. In conclusion, this is the largest Brazilian WES study involving families at high-risk for HBOC which has brought novel insights into the role of potentially new genetic risk factors for hereditary breast and ovarian cancer.

Premature rupture of membranes - A cause of foetal complications among lupus: A cohort study, systematic review and meta-analysis.

OBJECTIVE: The present study aimed to analyse the frequency of premature rupture of membranes (PROMs) among 190 women with systemic lupus erythematosus (SLE) followed up at the Hospital Universitário Pedro Ernesto from 2011 to 2018 and to review the literature on PROM in patients with SLE. METHODS: A cohort study of SLE patients was conducted by analysing the following variables: sociodemographic characteristics, clinical manifestations of lupus, modified disease activity index for pregnancy, drugs used during pregnancy, intercurrent maternal infections and obstetric outcomes. Additionally, seven electronic databases (PubMed, Embase, Cochrane, Scielo, Scielo Brazil, Virtual Health Library Regional Portal and Google Scholar) were systematically searched. The search was updated on 3 February 2020. RESULTS: Infections (relative risk (RR): 3.26, 95% confidence interval (CI): 1.5-6.7, p = .001), history of serositis (RR: 2.59, 95% CI: 1.31-5.11, p = .006) and anti-RNP positivity (RR: 3.08, 95% CI: 1.39-6.78, p = .005) were associated risk factors for PROM, while anti-RNP positivity (RR: 3.37, 95% CI: 1.35-8.40; p = .009) were associated with premature PROM (PPROM). The prevalence of PROM and PPROM was 28.7% and 12.9%, respectively. In the systematic review, the prevalence of PROM and PPROM was 2.7%-35% (I2 = 87.62%) and 2.8%-20% (I2 = 79.56%), respectively. CONCLUSIONS: PROM, both at term and preterm, occurs more frequently in women with lupus than in the general population. A history of serositis, anti-RN, infections and immunosuppression during pregnancy may increase the susceptibility to PROM. The systematic review did not find any study with the main objective of evaluating PROM/PPROM in women with lupus.