On methods for radiometric surveying in radiotherapy bunkers.

Radiometric surveys in radiotherapy bunkers have been carried out in Brazil for many years, both by the same radiotherapy facility for verification of shielding as by the regulatory agency for licensing and control purposes. In recent years, the Intensity Modulated Radiation Therapy (IMRT) technique has been gradually incorporated into many facilities. Therefore, it has been necessary to consider the increased leakage component that has an important impact on the secondary walls. For that, a radiometric survey method has been used that considers an increased 'time of beam-on' for the secondary walls. In this work we discuss two methods of doing this: the first considers that this 'time of beam-on' affects the sum of the two components, leakage and scattered. In another method it is considered that only the leakage component is affected by this extended 'time of beam-on'. We compare the methods and show that for secondary walls withU= 1 the first method overestimates dose rates by important percentages and for secondary walls withU< 1 it can both overestimate or underestimate the dose rates, depending on the parameters of the project. An optimized procedure is proposed, according to the use factor (U) of the secondary wall to be measured.

Risk of ovarian hyperstimulation syndrome in women with malignancies undergoing treatment with long-acting gonadotropin-releasing hormone agonist after controlled ovarian hyperstimulation for fertility preservation: a systematic review.

Background: Fertility preservation is an important quality of life issue for women of reproductive age undergoing gonadotoxic treatment. The possibility of administering an adjuvant long-acting gonadotropin-releasing hormone agonist (GnRHa) with the aim of reducing the number of follicles susceptible to the effects of chemotherapy and thus reducing the risk of ovarian damage is considered in some international society guidelines, particularly in certain cancers such as breast cancer. Nowadays, the administration of long-acting GnRHa after controlled ovarian hyperstimulation (COH) for fertility preservation by cryopreservation of oocytes or embryos is increasingly used. However, cases of ovarian hyperstimulation syndrome (OHSS) have been reported following the use of long-acting GnRHa after COH for fertility preservation, indicating that the potential adverse effects of this treatment need to be further investigated. Objectives: The aim of this systematic review was to comprehensively characterize patients who developed OHSS after treatment with long-acting GnRHa following COH for fertility preservation. Methods: A comprehensive search of major electronic databases through January 2023 was performed. Studies reporting the use of long-acting GnRHa after COH for fertility preservation and the development of OHSS were included. Risk of bias was assessed using a modified version of the Newcastle-Ottawa scale. Results were synthesized qualitatively. Results: Three studies with five patients met the eligibility criteria. The majority of patients were diagnosed with breast cancer and all patients underwent COH for oocyte cryopreservation. OHSS occurred in all patients after administration of long-acting GnRHa. The interval between ovulation induction and administration of long-acting GnRHa thereafter ranged from 3 to 5 days. All patients were treated conservatively and recovered without complications. Conclusion: Current evidence suggests that the use of long-acting GnRHa after COH for fertility preservation may be associated with OHSS. Healthcare providers should thoroughly discuss the benefits and risks of this intervention with their patients before making a decision. Further studies are needed to fully elucidate the causal relationship between long-acting GnRHa and OHSS in this population.

Feasibility and safety of combined laparoscopic and transvaginal oocyte retrieval in a woman with vaginal recurrence of cervical adenocarcinoma: a case report.

Introduction: Oocyte cryopreservation is an established technique for fertility preservation in women diagnosed with cancer. However, some clinical scenarios may preclude the commonly used transvaginal approach to oocyte retrieval. In such cases, a laparoscopic approach may be required. Here, we report the feasibility and safety of a combined laparoscopic and transvaginal approach for oocyte retrieval in a woman with vaginal recurrence of cervical adenocarcinoma. This approach allowed for oocyte cryopreservation prior to cancer treatment, representing a novel application in this clinical context. Methods: A 31-year-old woman with endocervical adenocarcinoma underwent laparoscopic radical hysterectomy and pelvic lymph node dissection. She presented with vaginal recurrence and was referred for fertility preservation by oocyte cryopreservation before chemotherapy and radiotherapy/brachytherapy. Ovarian stimulation was initiated with a gonadotropin antagonist protocol combined with aromatase inhibitors, and oocyte retrieval was performed with a combined laparoscopic and transvaginal approach. Results: A total of 18 oocytes were retrieved and 10 mature oocytes were cryopreserved. Peritoneal fluid cytology was negative for malignancy. The patient underwent chemotherapy and radiotherapy/brachytherapy and was disease-free after oocyte retrieval. Conclusion: The combined laparoscopic and transvaginal approach for oocyte retrieval emerges as a practical and efficacious method for fertility preservation in cases of cervical adenocarcinoma with vaginal recurrence. Further comprehensive studies are warranted to establish the reproducibility, safety, and long-term outcomes associated with this innovative approach.

Implementing a multisector public-private partnership to improve urban hypertension management in low-and middle- income countries.

BACKGROUND: Cardiovascular disease presents an increasing health burden to low- and middle-income countries. Although ample therapeutic options and care improvement frameworks exist to address its prime risk factor, hypertension, blood pressure control rates remain poor. We describe the results of an effectiveness study of a multisector urban population health initiative that targets hypertension in a real-world implementation setting in cities across three continents. The initiative followed the "CARDIO4Cities" approach (quality of Care, early Access, policy Reform, Data and digital technology, Intersectoral collaboration, and local Ownership). METHOD: The approach was applied in Ulaanbaatar in Mongolia, Dakar in Senegal, and São Paulo in Brazil. In each city, a portfolio of evidence-based practices was implemented, tailored to local priorities and available data. Outcomes were measured by extracting hypertension diagnosis, treatment and control rates from primary health records. Data from 18,997 patients with hypertension in primary health facilities were analyzed. RESULTS: Over one to two years of implementation, blood pressure control rates among enrolled patients receiving medication tripled in São Paulo (from 12·3% to 31·2%) and Dakar (from 6·7% to 19·4%) and increased six-fold in Ulaanbaatar (from 3·1% to 19·7%). CONCLUSIONS: This study provides first evidence that a multisectoral population health approach to implement known best-practices, supported by data and digital technologies, and relying on local buy-in and ownership, can improve hypertension control in high-burden urban primary care settings in low-and middle-income countries.

Effect of thyroid function on assisted reproduction outcomes in euthyroid infertile women: A single center retrospective data analysis and a systematic review and meta-analysis.

Background: The influence of thyroid-stimulating hormone (TSH) on gestational outcomes have been studied and checked whether differing TSH levels are relevant on human reproduction outcomes. International guidelines recommend TSH values <2.5 mIU/L in women trying to conceive, since values above this level are related to a higher frequency of adverse reproductive outcomes. This study aimed to evaluate whether TSH values correlate with different gestational outcomes in euthyroid infertile women without autoimmune thyroid disease. Methods: A retrospective cohort study was conducted involving 256 women who underwent in vitro fertilization (IVF) treatment. The participants were divided into two groups: TSH 0.5-2.49 mIU/L (n=211) and TSH 2.5-4.5 mIU/L (n=45). The clinical data, hormonal profiles and reproductive outcomes were compared between groups. Additionally, a systematic review with meta-analysis following the PRISMA protocol was carried out in PubMed/MEDLINE, EMBASE, and SciELO, with no time or language restrictions, for articles comparing TSH groups named "low TSH" (<2,5 mIU/L) and "high TSH" (≥2.5 mIU/L). A meta-analysis of proportions was performed with pooled estimates expressed as relative risk (RR) of events and a random effects model. Results: Age, BMI, free thyroxine levels (FT4) hormonal profile and IVF outcomes were not different between groups, neither gestational outcomes (p=0.982). Also, no difference was observed when the TSH and FT4 levels were compared between patients with positive or negative gestational outcomes (p=0.27 and p=0.376). Regarding the systematic review with meta-analysis, 17 studies from 2006 to 2022 were included, and added by this original retrospective research comprising 13.247 women undergoing IVF. When comparing the proportions of clinical pregnancy between the TSH groups, no significant difference was found (RR 0.93, 95% CI 0.80-1.08), with high between studies heterogeneity (I²: 87%; τ2: 0.0544; p<0.01). The number of deliveries was not significantly different between groups, despite a trend towards higher frequency in the high-TSH group (RR 0.96, 95% CI 0.90-1.02). Conclusion: Variation in TSH levels within the normal range was not associated with pregnancy and delivery rates in women, without autoimmune thyroid disease, who underwent IVF treatment. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD 42022306967.

Impact of blood levels of progesterone on the day of ovulation onset on clinical, laboratory and reproductive parameters of young patients undergoing assisted reproduction: a cross-sectional study.

OBJECTIVE: To assess whether there is an association between the level of progesterone on the day of administration of human chorionic gonadotropin and clinical and laboratory characteristics, in addition to the results of in vitro fertilization of patients with a good prognosis. METHODS: A cross-sectional study comprising 103 women who underwent intracytoplasmic sperm injection treatment, between November 2009 and May 2015, aged ≤35 years, with no comorbidities, with fresh embryo transfer. Data were collected from patient medical records. RESULTS: There was a weak positive correlation between the level of progesterone on the day of human chorionic gonadotropin and the number of follicles larger than 14mm (ß=0.02, p=0.001), retrieved oocytes (ß=0.01, p=0.01) and oocytes in metaphase II (MII) (ß=0.02, p=0.02); that is, the increase in progesterone level has a slight association with increased values of these variables. Body mass index was inversely correlated with progesterone level on the day of human chorionic gonadotropin (ß=-0.01, p=0.02). No association was found between the level of progesterone on the day of human chorionic gonadotropin and the protocols used for controlled ovarian stimulation, quality of transferred embryos and the pregnancy rate. CONCLUSION: There is an association between the value of progesterone on the day of human chorionic gonadotropin administration with body mass index, number of follicles larger than 14mm, number of retrieved oocytes and oocytes in metaphase II. Unlike embryo quality and pregnancy rate, which do not have a statistically significant relation with this value in the population studied.

Epidemiology of Urological Cancers in Brazil: Trends in Mortality Rates Over More Than Two Decades.

BACKGROUND: Considering the socioeconomic disparities and inequalities observed in the healthcare resources among the Brazilian regions, we aimed to analyze the mortality trends of urological cancers in Brazil to identify areas with differential risks. METHODS: Deaths related to prostate (PCa), bladder (BCa), kidney (KC), penile (PeC), and testis (TCa) cancers from 1996 to 2019 were retrieved from the Mortality Information System database (Brazil). Geographic and temporal patterns were analyzed using age-standardized mortality rates (ASMRs). A joinpoint regression model was used to identify changes in the trends and calculate the average annual percentage change (AAPC) for each region. RESULTS: In Brazil, the ASMRs (per 100,000 persons/year) were 11.76 for PCa; 1.37, BCa; 1.13, KC; 0.33, and PeC; 0.26, TCa over the period. Increasing mortality trends were registered for BCa (AAPC = 0.45 in men; 0.57 in women), KC (AAPC = 2.03 in men), PeC (AAPC = 1.01), and TCa (AAPC = 2.06). The PCa mortality presented a significant reduction after 2006. The Northeast and North regions showed the highest increases in the PCa mortality. The South registered the highest ASMRs for BCa and KC, but the highest increasing trends occurred in the men from the Northeast. The North presented the highest ASMR for PeC, while the South registered the highest ASMR for TCa. CONCLUSION: Differences among regions may be partly explained by disparities in the healthcare systems. Over the study period, the North and Northeast regions presented more discrepant mortality rates. Efforts should be made to ensure access to the healthcare resources for people at risk, particularly in these regions.

Should obesity be associated with worse urinary continence outcomes after robotic-assisted radical prostatectomy? a propensity score matching analysis.

PURPOSE: To analyze the association between obesity and urinary incontinence rate in men submitted to robot-assisted radical prostatectomy (RARP) in a high-volume cancer center. MATERIALS AND METHODS: We reported 1.077 men who underwent RARP as the primary treatment for localized prostate cancer from 2013 to 2017. Patients were classified as non-obese (normal BMI or overweight) or obese men (BMI ≥30kg/m2). They were grouped according to the age, PSA level, D'Amico risk group, Gleason score, ASA classification, pathological stage, prostate volume, salvage/adjuvant radiotherapy, perioperative complications, and follow-up time. Urinary continence was defined as the use of no pads. For the analysis of long-term urinary continence recovery, we conducted a 1:1 propensity-score matching to control confounders. RESULTS: Among the obese patients, mean BMI was 32.8kg/m2, ranging 30 - 45.7kg/m2. Only 2% was morbidly obese. Obese presented more comorbidities and larger prostates. Median follow-up time was 15 months for the obese. Complications classified as Clavien ≥3 were reported in 5.6% of the obese and in 4.4% of the non-obese men (p=0.423). Median time for continence recovery was 4 months in both groups. In this analysis, HR was 0.989 for urinary continence recovery in obese (95%CI=0.789 - 1.240; p=0.927). CONCLUSIONS: Obese can safely undergo RARP with similar continence outcomes comparing to the non-obese men when performed by surgeons with a standardized operative technique. Future studies should perform a subgroup analysis regarding the association of obesity with other comorbidities, intending to optimize patient counseling.

Impact of blood levels of progesterone on the day of ovulation onset on clinical, laboratory and reproductive parameters of young patients undergoing assisted reproduction: a cross-sectional study

ABSTRACT Objective: To assess whether there is an association between the level of progesterone on the day of administration of human chorionic gonadotropin and clinical and laboratory characteristics, in addition to the results of in vitro fertilization of patients with a good prognosis. Methods: A cross-sectional study comprising 103 women who underwent intracytoplasmic sperm injection treatment, between November 2009 and May 2015, aged ≤35 years, with no comorbidities, with fresh embryo transfer. Data were collected from patient medical records. Results: There was a weak positive correlation between the level of progesterone on the day of human chorionic gonadotropin and the number of follicles larger than 14mm (ß=0.02, p=0.001), retrieved oocytes (ß=0.01, p=0.01) and oocytes in metaphase II (MII) (ß=0.02, p=0.02); that is, the increase in progesterone level has a slight association with increased values of these variables. Body mass index was inversely correlated with progesterone level on the day of human chorionic gonadotropin (ß=-0.01, p=0.02). No association was found between the level of progesterone on the day of human chorionic gonadotropin and the protocols used for controlled ovarian stimulation, quality of transferred embryos and the pregnancy rate. Conclusion: There is an association between the value of progesterone on the day of human chorionic gonadotropin administration with body mass index, number of follicles larger than 14mm, number of retrieved oocytes and oocytes in metaphase II. Unlike embryo quality and pregnancy rate, which do not have a statistically significant relation with this value in the population studied.

Evaluation of anaesthetic depth and cardiopulmonary effects of propofol infusion rate in Sapajus apella previously chemically contained with dextroketamine-midazolam.

BACKGROUND: This study evaluated the cardiopulmonary effects and anaesthetic depth induced by a propofol infusion rate of 0.8 mg/kg/min in monkeys (Sapajus apella). MATERIALS AND METHODS: Five capuchin monkeys received dextroketamine-midazolam intramuscularly. After a maximum duration of 5 min, the values of the physiological parameters were recorded, and a venous catheter was placed. After recovery from chemical restraint, the animals were anaesthetized with propofol intravenously, which was maintained for 1 h. Physiological parameters, anaesthetic depth, the time and quality of anaesthetic recovery were evaluated. RESULTS: Heart and respiratory rates, systolic blood pressure and rectal temperature during propofol infusion were lower than those during anaesthesia induction with dextroketamine-midazolam. Unconsciousness, muscle relaxation and lack of response to tail clamping were observed during propofol infusion. No animals showed excitement or vocalization during anaesthetic recovery. CONCLUSION: Propofol infusion rate of 0.8 mg/kg/min promoted surgical general anaesthesia, with transient hypotension, which showed excellent anaesthetic recovery.

Prostate Cancer Screening in Brazil: a single center experience in the public health system.

PURPOSE: Incidence and mortality of prostate cancer (PCa) are still increasing in developing countries. Limited access to the health system or more aggressive disease are potential reasons for this. Ethnic and social differences in developed countries seem to make inappropriate to extrapolate data from other centers. We aim to report the epidemiological profile of a PSA-screened population from a cancer center in Brazil. MATERIALS AND METHODS: We retrospectively selected 9.692 men enrolled in a PCa prevention program, comprising total PSA level and digital rectal examination at the first appointment, associated with complementary tests when necessary. Men aged over 40 years-old were included after shared decision-making process. Prostate biopsy (TRUS) was performed when clinically suspected for PCa. After the diagnosis, patients underwent appropriate treatment. RESULTS: TRUS was performed in 5.5% of men and PCa incidence was 2.6%. Overall ratio between number of patients who needed to be screened in order to diagnose one cancer was 38.9 patients, with 2.1 biopsies performed to diagnose a cancer. Positive predictive value (PPV) of TRUS biopsy in this strategy was 47.2%, varying from 38.5% (<50 years-old) to 60% (>80 years-old). We evidenced 70 patients (27.9%) classified as low risk tumors, 74 (29.5%) as intermediate risk, and 107 (42.6%) as high-risk disease. CONCLUSIONS: PSA-screening remains controversial in literature. In front of a huge miscegenated people and considering the big proportion of high-risk PCa, even in young men diagnosed with the disease, it is imperative to inform patients and health providers about these data particularities in Brazil.

Cost-effectiveness analysis of robotic-assisted versus retropubic radical prostatectomy: a single cancer center experience.

Prostate cancer (PCa) treatment has been greatly impacted by the robotic surgery. The economics literature about PCa is scarce. We aim to carry-out cost-effectiveness and cost-utility analyses of the robotic-assisted radical prostatectomy (RALP) using the "time-driven activity-based cost" methodology. Patients who underwent radical prostatectomy in 2013 were retrospectively analyzed in a cancer center over a 5-year period. Fifty-six patients underwent RALP and 149 patients underwent retropubic radical prostatectomy (RRP). The amounts were subject to a 5% discount as correction of monetary value considering time elapsed. Calculation of the Incremental Cost-Effectiveness Ratios (ICER) related to events avoided and the Incremental Cost-Utility Ratio (ICUR) related to "QALY saved" were performed. QALY was performed using values of utility and "disutility" weights from the "Cost-Effectiveness Analysis Registry". Hypothetical cohorts were simulated with 1000 patients in each group, based on the treatment outcomes. Total and average costs were R$1,903,671.93, and R$12,776.32 for the RRP group, and R$1,373,987.26, and R$24,535.49 for the RALP group, respectively. The costs to treat the hypothetical cohorts were R$10,010,582.35 for RRP, and R$19,224,195.90 for RALP. ICER calculation evidenced R$9,213,613.55 of difference between groups. ICUR was R$ 22,690.83 per QALY saved. Limitations were the lack of cost-effectiveness analyses related to re-hospitalization rates and complications, single center perspective, and currency-translation differences. Medical fees were not included. RALP showed advantages in cost-effectiveness and cost-utility over RRP in the long term. Despite the increased costs to the introduction of robotic technology, its adoption should be encouraged due to the gains.

Prevalence of preeclampsia and eclampsia in adolescent pregnancy: A systematic review and meta-analysis of 291,247 adolescents worldwide since 1969.

OBJECTIVE: Hypertensive disorders are among the main causes of maternal and perinatal morbidity and mortality, and the findings regarding the occurrence of preeclampsia (PE) and eclampsia (E) in adolescent pregnancy are conflicting. We performed a systematic review and meta-analysis aimed to determining the prevalence of PE and E in adolescent pregnancy considering socioeconomic and temporal characteristics. STUDY DESIGN: MEDLINE, EMBASE and SciELO databases, with no time span restrictions. Studies that reported the occurrence of PE and E in adolescent pregnancy. Study selection, data extraction and bias assessment were performed by three independent investigators. Meta-analysis techniques comprised random-effects model and double-arcsine transformation; χ1 and I2 tests were used to assess heterogeneity. Meta-regression used Hunter-Schmidt model; publication bias were assessed by funnel and Baujat plots. RESULTS: Seventy studies were included, ranging from 1969 to 2019 and comprising 30 countries and 291,247 adolescents. The overall prevalence rate of PE/E was 6.7 % (95 % CI = 5.8-7.6). Subgroup analysis revealed association of PE/E (P = 0.050) and E (P = 0.0113) with country income, and the highest prevalences were found in low-and medium-income country groups (11.5 %, 95 % CI=7.8-15.8 and 10.6 %, 95 % CI=6.05-16.2). Association of PE with publication year (P = 0.0022) was also found with an observable reduction in prevalence rate across the years. CONCLUSIONS: The findings seem to confirm that socioeconomic and demographic characteristics play a role for the risk of PE/E in adolescent pregnancy. Although the occurrence of PE has declined worldwide, the problem has broader dimensions beyond health issues.

The role of Kisspeptin levels in polycystic ovary syndrome: a systematic review and meta-analysis.

PURPOSE: Polycystic ovarian syndrome (PCOS) is a complex and not fully elucidated pathology. This prevalent endocrinopathy affects patients in reproductive age, impacts on estrogen-dependent diseases, as well as in infertility. In this context, Kisspeptin (KP) may be considered a potential biomarker for PCOS diagnosis and follow-up. Here, we aimed to verify the levels of KP in obese and non-obese patients with PCOS, their relationship with other hormones, in comparison to healthy controls. METHODS: A systematic review and meta-analysis were performed according to the PRISMA guidelines. We searched MEDLINE, EMBASE, PsycINFO, Global Health, The Cochrane Library, Health Technology Assessment Database, and Web of Science for eligible studies. A random effects model meta-analysis of standardized mean difference (SMD) was conducted and the I2 was used to assess heterogeneity. Meta-regression was conducted through mixed-effects model. RESULTS: A total of 12 studies were included, comprising 660 PCOS patients and 600 controls. The KP levels were lower in the control group (0.76: 0.17-1.35; 95% CI). In the subgroup analyses, patients were divided in non-overweight/obese (BMI < 25) and overweight/obese (BMI ≥ 25) groups. The meta-regression revealed a difference between the obese and non-obese groups (z = 2.81; p = 0.0050). CONCLUSIONS: PCOS patients showed higher KP levels than control, and obese non-PCOS patients also showed altered KP levels. All studies had poor descriptions of sample collection, pre-analytical and analytical procedures, which is critical considering structural characteristics of the KP molecule.

Effects of a Polymorphism in the Promoter Region of the Follicle-Stimulating Hormone Subunit Beta (FSHB) Gene on Female Reproductive Outcomes.

BACKGROUND: Follicle-stimulating hormone (FSH) is essential to the hypothalamic-pituitary-gonadal axis, playing a key role in human reproduction. It is a heterodimer comprised of a hormone-specific ß-chain (FSH-ß) that is associated with an α-chain. It exerts its biological activities by binding to the FSH receptor (FSHR). The ß-subunit, which is encoded by the FSHB gene, is responsible for ensuring binding specificity to the FSHR. There is a promoter polymorphism in this gene, c.-211G>T (rs10835638), upstream of the transcription start site; and in vitro studies have reported that the T allele decreases FSHB transcription in gonadotrophic cells. AIMS: Investigate the possible effects of the FSHB c.-211G/T polymorphism on hormonal profile and in in vitro fertilization (IVF)/intracytoplasmic sperm injection outcomes in normoovulatory Brazilian women. METHODS: A cross-sectional study of 140 women (median age = 33 years [CI: 32-34]) with infertility mainly caused by male (n = 85) or tuboperitoneal (n = 55) factors. In this study we evaluated FSH, estradiol, luteinizing hormone (LH), progesterone, prolactin and anti-Mullerian hormone levels, and antral follicle counting (AFC). Genotyping was performed using the TaqMan real-time polymerase chain reaction methodology. RESULTS: The wild-type allele G was found in 86.4% and the polymorphic allele T in 13.6% of the women respectively. The TT genotype was not found in any women. Women carrying the GT genotype had a poorer response more frequently to controlled ovarian hyperstimulation when compared to individuals with the GG genotype (47.4% vs. 26.5%, p = 0.010), higher LH levels (3.1 IU/mL vs. 2.4 IU/mL, p = <0.001), lower AFC (8.0 vs. 10.0, p = 0.03), oocytes retrieved (3.0 vs. 5.0, p = 0.03), MII (3.0 vs. 4.0, p = 0.02), and embryos (2.0 vs. 3.0, p = 0.02). Despite these findings, no difference was observed in pregnancy rate. CONCLUSION: Our findings suggest that the FSHB c.-211G/T polymorphism may modestly alter some aspects of the female reproductive system, but they are not associated with significantly different IVF outcomes.

Kisspeptin/GPR54 System: What Do We Know About Its Role in Human Reproduction?

Kisspeptin is involved in the control of human reproduction bridging the gap between the sex steroid levels and feedback mechanisms that control the gonadotropin releasing hormone (GnRH) secretion; however, studies considering this peptide and infertility are limited. We conducted a review and critical assessment of available evidence considering kisspeptin structure, physiology, function in puberty and reproduction, its role in assisted reproduction treatments, kisspeptin dosage and the impact on KISS1 and GPR54 genes. Literature searches were conducted in PubMed using keywords related to: (i) kisspeptin or receptors, kisspeptin-1 (ii) reproduction or infertility or fertility (iii) gene and (iv) dosage or measurement or quantification or serum level, in human. Kisspeptin is a product of KISS1 gene that binds to a G-protein-coupled receptor (GPR54/KISS1R) stimulating the release of GnRH by hypothalamic neurons, leading to secretion of pituitary gonadotropins (LH and FSH) and sexual steroids, which in turn will act in the gonads to produce the gametes. Kisspeptin is being recognized as a crucial regulator of the onset of puberty, the regulation of sex hormone mediated secretion of gonadotropins, and the control of fertility. Inactivating and activating mutations in both KISS1 or GPR54 genes were associated with hypogonadotropic hypogonadism and precocious puberty. Despite this, studies considering kisspeptin and infertility are scarce. The understanding of the role of kisspeptin may lead to its use as a biomarker in infertility treatments and use in controlled ovarian hyperstimulation.

PROGINS Polymorphism of the Progesterone Receptor Gene and the Susceptibility to Uterine Leiomyomas: A Systematic Review and Meta-Analysis.

AIMS: Steroid hormones play a central role in modulating the growth of uterine leiomyoma, and several studies have suggested that polymorphisms in genes encoding these hormones and their receptors may be risk factors for developing the disease. Progesterone is a potent antagonist of estrogen-induced proliferation in the endometrium, and the PROGINS polymorphisms have been associated with leiomyoma, but the results are inconsistent. In this study, we aimed to investigate the possible associations between the PROGINS polymorphisms and uterine leiomyoma. MATERIALS AND METHODS: MEDLINE using PubMed, Science Direct, and Google Scholar databases was searched using the terms "PROGINS," "progesterone receptor," "polymorphism," and "leiomyoma." We estimated risk with odds ratios [ORs] and 95% confidence intervals using standard genetic models (homozygous, recessive, dominant, and codominant). RESULTS: Six studies were included in this meta-analysis based on 837 cases and 1011 controls. Subjects in three studies were Asian (365 cases/391 controls), and five were non-Asian (472 cases/620 controls). Our findings showed no association between PROGINS and leiomyoma in the overall analysis (OR 0.91-1.07, p = 0.15-0.57) nor in either of the subgroups (Asian: OR 0.84-1.04, p = 0.68-0.98; or non-Asian: OR 0.77-1.34, p = 0.33-0.93), in all genetic models. CONCLUSION: The PROGINS polymorphisms cannot be considered a risk factor for developing uterine leiomyoma.

CYP genes in osteosarcoma: Their role in tumorigenesis, pulmonary metastatic microenvironment and treatment response.

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The present study investigated the expression of Cytochrome P-450 (CYP) genes: CYP1A2, CYP3A4 and CYP3A5 by qRT-PCR in 135 specimens obtained from OS patients, including biopsy (pre-chemotherapy), tumor resected in surgery (post-chemotherapy), adjacent bone to tumor (nonmalignant tissue), pulmonary metastasis and adjacent lung to metastasis (nonmalignant tissue). Normal bone and normal lung tissues were used as control. We also investigated in five OS cell lines the modulation of CYPs expression by cisplatin, doxorubicin and methotrexate. As result, the adjacent lung specimens presented CYP1A2 overexpression compared to the normal lung (p=0.0256). Biopsy specimens presented lower CYP3A4 expression than normal bone (p=0.0314). The overexpression of both CYP1A2 and CYP3A4 in post-chemotherapy specimens were correlated with better event free-survival (p=0.0244) and good response (p=0.0484), respectively. Furthermore, in vitro assays revealed that CYP1A2 was upregulated by doxorubicin (p=0.0034); CYP3A4 was upregulated by cisplatin, doxorubicin and methotrexate (p=0.0004, p=0.0024, p<0.0001, respectively); and CYP3A5 was downregulated by doxorubicin (p=0.0285) and upregulated in time-dependent manner by methotrexate (p=0.0239). In conclusion, our findings suggest that CYP genes play an important role in OS tumorigenesis, at primary and metastatic sites, as well in treatment response.

Implementation of the trauma registry as a tool for quality improvement in trauma care in a brazilian hospital: the first 12 months.

OBJECTIVE: to analyze the implementation of a trauma registry in a university teaching hospital delivering care under the unified health system (SUS), and its ability to identify points for improvement in the quality of care provided. METHODS: the data collection group comprised students from medicine and nursing courses who were holders of FAPESP scholarships (technical training 1) or otherwise, overseen by the coordinators of the project. The itreg (ECO Sistemas-RJ/SBAIT) software was used as the database tool. Several quality "filters" were proposed to select those cases for review in the quality control process. RESULTS: data for 1344 trauma patients were input to the itreg database between March and November 2014. Around 87.0% of cases were blunt trauma patients, 59.6% had RTS>7.0 and 67% ISS<9. Full records were available for 292 cases, which were selected for review in the quality program. The auditing filters most frequently registered were laparotomy four hours after admission and drainage of acute subdural hematomas four hours after admission. Several points for improvement were flagged, such as control of overtriage of patients, the need to reduce the number of negative imaging exams, the development of protocols for achieving central venous access, and management of major TBI. CONCLUSION: the trauma registry provides a clear picture of the points to be improved in trauma patient care, however, there are specific peculiarities for implementing this tool in the Brazilian milieu.

Prognostic factors in patients with penile carcinoma and inguinal lymph node metastasis.

OBJECTIVES: To identify prognostic factors in patients with penile carcinoma and confirmed lymph node metastasis. METHODS: Patients were selected from a historical series of patients with penile carcinoma. An experienced pathologist reviewed all cases. Information regarding the total number of lymph nodes excised, the number of positive lymph nodes and the presence of extranodal extension were used. Lymph node ratio was categorized as <0.15 and >0.15. RESULTS: The 5-year recurrence-free survival and disease-specific survival rates were 55.3% and 64.1%, respectively. Lymphovascular invasion, lymph node ratio and pN status influenced survival rates in univariate analysis. Lymphovascular invasion and lymph node ratio remained as independent predictors of disease-specific survival and recurrence-free survival in the multivariate analysis. A risk stratification of death and tumor recurrence was observed when patients were grouped into three categories: absence of risk factors; the presence of one risk factor; and the presence of two or more risk factors. CONCLUSIONS: The presence of one or more of the following parameters is correlated with a significantly higher risk of death and tumor recurrence in patients with penile carcinoma and inguinal lymph node metastasis: extranodal extension, lymph node ratio >0.15 and lymphovascular invasion.