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Resumo Introdução: o Mesotelioma Peritoneal Maligno (MPM) é uma doença rara e letal com variável grau de agressividade. A morbimortalidade está relacionada com a carga de doença tumoral e a sobrevida mediana sem tratamento é de cerca de 12 meses. Quimioterapia baseada em cisplatina é o tratamento padrão nos casos de doença avançada irressecável, ou nos pacientes que declinam cirurgia, associado a quimioterapia hipertérmica intraperitoneal (HIPEC). Desenvolvimento: paciente, 54 anos, com histórico de perda ponderal, desconforto e aumento progressivo de volume abdominal, com imagem evidenciando espessamento peritoneal difuso e ascite, foi submetido a laparoscopia e biópsia com achados positivos para MPM, sendo realizada quimioterapia de 3ª linha com cisplatina e gemcitabine, seguido de manutenção com gemcitabine, apresentando resposta completa, sendo, portanto, caso de resposta excepcional e atípica para doença. Considerações finais: Apesar dos fatores de prognóstico desfavoráveis e rápida progressão aos esquemas iniciais, o paciente do caso apresentou melhora clínica importante e ausência de doença mensurável com esquema de cisplatina e gemcitabine, seguido de gemcitabine de manutenção. Comparado com dados vigentes na literatura, tal resposta é excepcional e atípica, haja vista as características biológicas tumorais da doença. Palavras-chave: Neoplasias Peritoneais; Oncologia; Antineoplásicos Alquilantes; Antimitóticos Abstract Objective: Malignant peritoneal mesothelioma (MPM) is a rare and lethal disease with variable degree of aggressiveness. Morbidity and mortality are related to the burden of tumor disease and median survival without treatment is about 12 months. Cisplatin-based chemotherapy is the standard of treatment in cases of advanced unresectable disease or in patients who decline surgery associated with intraperitoneal hyperthermic chemotherapy (HIPEC). Development: a 54-year-old patient with a history of discomfort, progressive increase in abdominal volume and weight loss, with an image showing diffuse peritoneal thickening and ascites, underwent laparoscopy and biopsy with positive findings for MPM, undergoing 3rd-line chemotherapy with cisplatin and gemcitabine, followed by maintenance with gemcitabine, showing a complete response, therefore being an exceptional and atypical response to disease. Final considerations: Despite the unfavorable prognostic factors and rapid progression to the initial regimens, the patient showed significant clinical improvement and absence of measurable disease with cisplatin and gemcitabine regimen, followed by maintenance gemcitabine. Compared with data from the literature, exceptional and atypical presentation, due to the tumor's biological characteristics of the disease. Keywords: Peritoneal Neoplasms; Medical Oncology; Antineoplastic Agents, Alkylating; Antimitotic Agents

Introduction The use of perioperative chemotherapy (CT) in patients with advanced gastric carcinoma increases their overall survival. This therapy may also increase the number of patients with R0 resection. Potential drawbacks of this therapy, besides its toxicity, include increased surgical morbidity. Methods We retrospectively evaluated the records of patients undergoing gastrectomy with curative intent, for carcinoma, at our institution between January 2009 and August 2018. They were divided into two groups: direct surgery (SURG) and perioperative CT (CHEMO). Patients with other neoadjuvant therapies and cardia Siewert I and II carcinomas were excluded. The primary objective was to evaluate the impact of perioperative CT on surgical morbidity. As secondary objectives, resection radicality and total lymph node count were compared between the two groups. Results A total of 307 patients (97 direct surgery and 210 perioperative CT) were evaluated. Median age was 67 years old. The overall major surgical morbidity (Clavien-Dindo 3–5) was 10.6% in the CHEMO group and 12.4 in the SURG group (p = 0.643). There was no statistically significant difference between the surgical radicality (R0 98% in the SURG group vs 97.5% CHEMO group (p = 0.865). There was an increase in the total number of lymph nodes retrieved in the specimen in the CHEMO group (25 vs 22, p = 0.001), a difference that was not maintained in the subgroup analysis as a function of the surgery performed. Conclusions Perioperative CT in gastric carcinoma does not increase surgical morbidity, surgical radicality and total lymph node count.

Introduction AKCEA-TTR-LRx is a ligand-conjugated antisense (LICA) drug in development for the treatment of hereditary transthyretin amyloidosis (hATTR), a fatal disease caused by mutations in the transthyretin (TTR) gene. AKCEA-TTR-LRx shares the same nucleotide sequence as inotersen, an antisense medicine approved for use in hATTR polyneuropathy (hATTR-PN). Unlike inotersen, AKCEA-TTR-LRx is conjugated to a triantennary N-acetylgalactosamine moiety that supports receptor-mediated uptake by hepatocytes, the primary source of circulating TTR. This advanced design increases drug potency to allow for lower and less frequent dosing. The NEURO-TTRansform study will investigate whether AKCEA-TTR-LRx is safe and efficacious, with the aim of improving neurologic function and quality of life in hATTR-PN patients. Methods/Design Approximately 140 adults with stage 1 (independent ambulation) or 2 (requires ambulatory support) hATTR-PN are anticipated to enroll in this multicenter, open-label, randomized, phase 3 study. Patients will be assigned 6:1 to AKCEA-TTR-LRx 45 mg subcutaneously every 4 weeks or inotersen 300 mg once weekly until the prespecified week 35 interim efficacy analysis, after which patients receiving inotersen will receive AKCEA-TTR-LRx 45 mg subcutaneously every 4 weeks. All patients will then receive AKCEA-TTR-LRx through the remainder of the study treatment period. The final efficacy analysis at week 66 will compare the AKCEA-TTR-LRx arm with the historical placebo arm from the phase 3 trial of inotersen (NEURO-TTR). The primary outcome measures are between-group differences in the change from baseline in serum TTR, modified Neuropathy Impairment Score + 7, and Norfolk Quality of Life—Diabetic Neuropathy questionnaire. Conclusion NEURO-TTRansform is designed to determine whether targeted delivery of AKCEA-TTR-LRx to hepatocytes with lower and less frequent doses will translate into clinical and quality-of-life benefits for patients with hATTR-PN. Trial Registration The study is registered at ClinicalTrials.gov (NCT04136184) and EudraCT (2019-001698-10). Supplementary Information The online version contains supplementary material available at 10.1007/s40120-021-00235-6., Plain Language Summary Hereditary transthyretin amyloidosis with peripheral neuropathy (hATTR-PN for short) is a rare inherited condition.In hATTR-PN, a protein called transthyretin (TTR for short) builds up and damages nerves throughout the body.This neuropathy causes symptoms such as weakness, loss of sensation, and pain.Currently available medicines can slow disease progression, but researchers are looking for more effective treatments with fewer side effects.AKCEA-TTR-LRx is an investigational treatment for hATTR-PN.AKCEA-TTR-LRx prevents the liver from making TTR, reducing the amount that causes disease progression.It is similar to an existing treatment called inotersen, but designed for better delivery to the liver and is more potent.This article describes the NEURO-TTRansform study that will evaluate how effective AKCEA-TTR-LRx is for treating hATTR-PN.Around 140 adults with hATTR-PN from the USA, Canada, and Europe will be able to take part in this study.The study treatment period will be 85 weeks long. People will receive injections underneath the skin of either:AKCEA-TTR-LRx every 4 weeks, orInotersen once a week for 35 weeks, followed by a switch to AKCEA-TTR-LRx every 4 weeks.People may continue to receive AKCEA-TTR-LRx after the study treatment period ends.In this study, researchers will compare results from people who received AKCEA-TTR-LRx to results from people who received no active ingredients (called placebo) in a similar study (called NEURO-TTR).Researchers will measure the differences in peoples’:Neuropathy symptoms.Quality of life.TTR protein levels in the blood. Supplementary Information The online version contains supplementary material available at 10.1007/s40120-021-00235-6.

Estima-se que até 75% dos pacientes com dispositivos cardíacos eletrônicos implantáveis (DCEIs) terão indicação de exame de ressonância nuclear magnética (RNM) ao longo da vida. Pelas características dos dispositivos, esses foram excluídos historicamente do rol de pacientes considerados elegíveis ao exame.

It is estimated that up to 75% of patients with cardiac implantable electronic devices (CIEDs) will have an indication for nuclear magnetic resonance imaging (MRI) throughout their lives. Th is population has been historically excluded from the list of patients considered eligible for this examination due to the characteristics of the devices.

Objective: Chemotherapeutic-induced peripheral neuropathy is one of the most common side effects of breast cancer treatment. Such a condition impacts on quality of life and has repercussions in treatment. The aim of this study was to correlate, by literature review, the risk factors and impact of peripheral neuropathy in women with breast cancer treated with taxanes. Methodology: This is a systematic review to assess the risk factors associated with peripheral neuropathy related to taxane. The literature review consisted of searching the MEDLINE database. The terms used were “neuropathy” or “chemotherapy” or “breast cancer” or “taxane,” using filters in accordance with the inclusion criteria. Only randomized controlled clinical trials were included in the selection, with full text available in the database, in English, published in the last 5 years, with women above 19 years old with breast cancer. Results: Six trials were included in this literature review. In total, 3,026 patients were evaluated and the main outcomes were to assess the main risk factors related to the shortand long-term effects of chemotherapy-induced peripheral neuropathy. Bandos et al. showed 41.9% of peripheral neuropathy within 2 years after starting treatment. Quintela et al. showed that patients with telomeric shortening had more toxicity related to paclitaxel. Hagoiwara et al. showed that peripheral neuropathy influenced lower scores on the quality of life scale. Ciruelos et al. showed greater delay and dose reduction in patients with neuropathy. Lam et al. showed a rate of neuropathy grade ≥1 in 67% of women. Conclusions: The results include presenting symptoms of peripheral neuropathy before the start of chemotherapy, the cumulative dose of the taxane agent, female gender, advanced age, body surface area, and hyperglycemia predispose to taxane-induced peripheral neuropathy. The heterogeneity between individuals with regard to susceptibility to taxane-induced peripheral neuropathy can be attributed to individual genetic differences.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract. Oesophageal GISTs are extremely uncommon, accounting for 0.7% of all GISTs, and their management is surrounded by some debate. We report a case of a 70-year-old man who was incidentally diagnosed with an oesophageal lesion on a 18F-fluorodeoxyglucose positron emission tomography. An endoscopic study revealed a non-obstructing 40 mm oesophageal lesion. Endoscopic ultrasound showed a well-circumscribed submucosal tumour on the middle oesophagus. Fine-needle aspiration was positive for CD117 and the overall features were of a GIST. After an initial thoracoscopic approach, the tumour was completely enucleated through a thoracotomy incision. The patient experienced no surgical complications and was discharged on day 4. Histopathology and immunohistochemical staining confirmed a low-risk GIST.

Purpose Neoadjuvant chemoradiotherapy (nCRT) followed by surgery in patients with resectable esophageal or esophagogastric junctional (GEJ) (Siewert I) cancer is associated with long term overall survival benefits. Up to one third of all patients submitted to nCRT present pathological complete response (pCR). 18F-fluorodeoxyglucose positron emission tomography with CT (18F-FDG PET-CT) is an important tool for assessing treatment response. Purpose was to assess retrospectively the power of 18F-FDG PET-CT in predicting pCR to evaluate the feasibility of a “watch and wait” approach. Patients and methods Retrospective analysis of a prospective database with esophageal or GEJ submitted to pre-operative chemoradiation. Pre and pos treatment 18F-FDG PET-CT were reviewed and classified using visual assessment and PERCIST criteria and the values of maximum standard uptake value were also recorded. Patients were classified as pCR or non-PCR. 18F-FDG PET-CT and pathological findings were compared against each other. Results Forty-three patients were included. The median age was 67 years and 90.7% were male. All patients underwent preoperative CRT and were evaluated with 18F-FDG PET-CT pre and post treatment. Transthoracic surgery was performed in all patients. Histological type was adenocarcinoma in 37% and squamous cell carcinoma in 58%. pCR was achieved in 56% of cases. Visual assessment of 18F-FDG PET-CT showed overall sensitivity 57.9%, specificity 62.5% and PERCIST criteria had 100% sensibility and 16.7% specificity. Conclusions 18F-FDG PET-CT is not an ideal predictor of pCR but if we use the PERCIST criteria we will have a high sensitivity and negative predictive value, avoiding false negative scans.

Background Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is a fatal condition, leading to heart failure (HF) and ultimately death. ATTR-CM is caused by misfolding and aggregation of transthyretin (TTR), a protein produced by the liver. Depending on the presence or absence of a destabilizing mutation in the TTR gene, the disease can be classified as hereditary ATTR-CM (hATTR-CM) or wild-type ATTR-CM (wtATTR-CM), respectively. Despite the treatment with a TTR stabilizer, tafamidis, recently approved in the United States for the treatment of ATTR-CM, disease progression still occurs. AKCEA-TTR-LRX (ION-682884) is an antisense oligonucleotide (ASO) that inhibits the production of TTR. It has a similar design and sequence as inotersen (the parent compound), but is conjugated to a triantennary N-acetyl galactosamine (GalNAc3) moiety for selective receptor-mediated delivery to hepatocytes, the principal source of systemically circulating TTR. This delivery approach has yielded an up to 30-fold increase in potency and improved the safety and tolerability profiles of ASOs in human clinical trials. Conjugation of this ligand allows the use of a lower dose to achieve improved pharmacodynamic results. In a phase 1, randomized, placebo-controlled study, AKCEA-TTR-LRX given at a 45 mg, 60 mg or 90 mg dose, by subcutaneous (SC) injection every four weeks in 36 healthy volunteers achieved a mean pre-steady state reduction in serum TTR of 86%, 91% and 94%, respectively, compared to baseline. The dosage regimen of 45 mg SC every four weeks (27-fold lower exposure vs the inotersen dose in NEURO-TTR trial) was chosen for the pivotal phase 3 study. Methods CARDIO-TTRansform (ClinicalTrials.gov NCT04136171) is a Phase 3 global, double-blind, randomized, placebo-controlled study assessing the efficacy and safety of AKCEA-TTR-L Rx in hATTR-CM or wtATTR-CM patients receiving available background standard of care (SoC) therapy. Approximately 750 patients around the world with a history of HF due to ATTR-CM will be randomized 1:1 to receive either AKCEA-TTR-LRx 45 mg or placebo administered by SC injection once every 4 weeks. Key inclusion criteria include diagnosis of ATTR-CM by biopsy or positive PYP/DPD/HMDP scan, interventricular septum thickness >12mm, NT-proBNP > 600 pg/mL, NYHA class I-III and 6-minute walk distance (6MWD) >150 m. Key exclusion criteria include, platelet count = 750 mg/g. Concomitant treatment with tafamidis as SoC for ATTR-CM is allowed. The study consists of a 120-week Treatment Period. Primary efficacy endpoint is the composite of cardiovascular (CV) mortality and recurrent CV clinical events at Week 120 study visit using the Andersen-Gill method. Secondary endpoints include the change from baseline in the 6MWD, KCCQ score, CV clinical events, CV death and all-cause of mortality at Week 120. Conclusions Despite recent advances, additional efficacious, safe and convenient treatment options for ATTR-CM are needed. The CARDIO-TTRansform trial is a large Phase 3 trial designed to evaluate the clinical efficacy and safety of AKCEA-TTR-LRx compared to placebo in patients with ATTR-CM receiving available SoC therapy.

Esta dissertação analisa a exceção de ofensa à ordem pública como causa de recusa do reconhecimento e/ou execução da sentença arbitral estrangeira. Busca-se inicialmente determinar o conceito de ordem pública e sua extensão. Antes disso, contudo, elabora-se um breve panorama sobre sentença estrangeira e arbitragem comercial internacional, faz-se um apanhado histórico da homologação de sentença estrangeira no Brasil, analisa-se os aspectos gerais da homologação de sentenças arbitrais estrangeiras, as normas de origem interna e os tratados internacionais com vigência no Brasil, o procedimento homologatório e os pressupostos positivos e negativos da homologação. Após, analisa-se a ordem pública interna, internacional e transnacional, assim como a ordem pública processual e material. Em seguida, examina-se a extensão que a doutrina e a jurisprudência têm conferido ao conceito de ordem pública de que trata o art. V (2) (b) da Convenção de Nova Iorque e o art. 39, II da Lei nº. 9.307/96. Posteriormente, analisa-se alguns temas que já suscitaram questionamentos de ofensa à ordem pública, os casos já julgados pelo STF e STJ de homologação de sentenças arbitrais estrangeiras com alegação de ofensa à ordem pública e como o posicionamento do Judiciário, sob o enfoque da Análise Econômica do Direito, afeta os custos de transação dos negócios comerciais. Defende-se ao final do trabalho a necessidade de se restringir o campo de aplicação e o alcance dos questionamentos de ofensa à ordem pública. O objetivo do estudo é demonstrar que a ordem pública deve ser interpretada restritivamente e que a intervenção deve ser excepcional. This Masters degree thesis analyzes the exception given to public policy offenses as a cause for the refusal of recognition and/or enforcement of foreign arbitral awards. This research initially attempts to define the concept of public policy and its extension. Prior to that, however, a brief analysis of foreign awards and international commercial arbitration as well as a historical overview of homologation in Brazil are drawn, and the general aspects of the recognition of foreign arbitral awards and the internal rules and international treaties which are effective in Brazil, the homologation proceeding itself, and both the positive and negative aspects of homologations are analyzed. Afterwards, the domestic, international and transnational public policies are analyzed, as well as the procedural and material public policy. Following, the meaning that the doctrine and jurisprudence have given to the concept of public policy presented in the Article V (2) (b) of the New York Convention, and in the Article 39 of Law No. II. 9.307/96 is examined. Later, some issues that have raised questionings related to public policy offenses are analyzed, as well as the cases already ruled by the Brazilian Supreme Court and the Superior Court of Justice for the homologation of foreign arbitral awards with alleged public order offenses and how the position of the judiciary, from the perspective of Economic Analysis of Law, affects transaction costs of business affairs. Finally, the need to limit both the scope of applications and the range of questionings concerning public policy offenses is defended. The main goal of this study is to demonstrate that public policy shall be strictly interpreted and that intervention must be exceptional.

Background: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is a life-threatening, irreversible condition, which can lead to heart failure (HF) and, ultimately, heart transplant or death. Despite the recent approval in United States of a TTR stabilizer (VYNDAQEL®-tafamidis meglumine;VYNDAMAX™-tafamidis) for the treatment of ATTR-CM, disease progression still occurs. This study aims to determine if treatment with AKCEA-TTR-LRx (ION-682884), an antisense oligonucleotide (ASO), is safe and superior to placebo in reducing the risk of cardiovascular (CV) death or CV clinical events in patients with hereditary (hATTR-CM) or wild-type ATTR-CM (wtATTR-CM). Study Design and Methods: AKCEA-TTR-LRx (ION-682884) is a follow-on compound that incorporates the Ligand-Conjugated Antisense (LICA) technology; in this case, a triantennary N-acetyl galactosamine (GalNAc) moiety which targets the asialoglycoprotein receptors (ASGPR) expressed abundantly on the hepatocyte cell surface. In comparison to inotersen, its parent compound, ION-682884 requires a lower dose and frequency of administration (27-fold smaller; 45mg SC Q4W) to achieve a similar reduction in ATTR, providing greater patient convenience. ION-682884-CS2 (EudraCT No: 2019-002835-27) is a Phase 3 global, double-blind, randomized, placebo-controlled study assessing the efficacy and safety of AKCEA-TTR-LRx (ION-682884) in hATTR-CM or wtATTR-CM patients receiving available background standard of care (SoC) therapy. Approximately 750 patients with a history of HF due to ATTR-CM will be randomized 1:1 to receive AKCEA-TTR-LRx (ION-682884) or placebo administered by subcutaneous injection once every 4 weeks. The main inclusion criteria include confirmed diagnosis of ATTR-CM by tissue biopsy or positive PYP/DPD scan, end-diastolic interventricular septum thickness of >12mm, NT-proBNP >600 pg/mL, NYHA class I-III and 6-minute walk distance (6MWD) >150 m. The main exclusion criteria include estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2, platelet count below the low limit of normality and urine protein/creatinine ratio (UPCR) ≥ 1000 mg/g. Patients are allowed to concomitantly receive tafamidis/tafamidis meglumine as SoC for ATTR-CM, if locally approved and available, per physician's discretion. The study consists of a 120-week Treatment Period and a 20-week Post-Treatment Evaluation Period. During each study visit, subjects will undergo laboratory tests, cardiac assessments (echocardiography), and functional evaluations. Patient-reported outcomes (PRO) will also be collected. Primary efficacy endpoint is the composite of CV mortality and frequency of CV clinical events (HF-related urgent visits requiring administration of IV diuretics and/or CV-related hospitalizations) at Week 120 study visit, analyzed by the Finkelstein-Shoenfeld method. This test is based on the principle of each patient in the study being compared with every other patient in a pairwise manner in hierarchical fashion. Secondary endpoints include the change from baseline in the 6MWD, Kansas City Cardiomyopathy Questionnaire score, rate of CV mortality, CV clinical events, and all-cause of mortality at Week 120. Additional exploratory endpoints include a change from baseline in cardiac imaging parameters, renal function, biomarkers, and PROs questionnaires and disease scores. An interim analysis on change from baseline in 6MWD is also planned at Week 60. All deaths and CV clinical events will be adjudicated by an independent, blinded Clinical Adjudication Committee, using predefined endpoint criteria. Conclusions: Despite recent advances, there is still a need for more efficacious, safe and convenient treatment options for ATTR-CM. The ION-682884-CS2 is a large Phase 3 trial designed to evaluate the clinical efficacy and safety of AKCEA-TTR-LRx (ION-682884) compared to placebo for the treatment of ATTR-CM. Figure Disclosures Falk: Ionis Pharmaceuticals: Consultancy. Gertz:Ionis/Akcea: Consultancy; Alnylam: Consultancy; Proclara: Membership on an entity's Board of Directors or advisory committees; Prothena Biosciences Inc: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Spectrum: Consultancy, Research Funding; Annexon: Consultancy; Appellis: Consultancy; Amgen: Consultancy; Medscape: Consultancy, Speakers Bureau; Physicians Education Resource: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Research to Practice: Consultancy; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; i3Health: Other: Development of educational programs and materials; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding; International Waldenstrom Foundation: Research Funding. Benson:Ionis Pharmaceuticals: Research Funding. Buchele:Ionis Pharmaceuticals: Employment. Brambatti:Ionis Pharmaceuticals: Employment. Tsimikas:Ionis Pharmaceuticals: Employment. Viney:Ionis Pharmaceuticals: Employment. Tai:Ionis Pharmaceuticals: Employment. Monteiro:Ionis Pharmaceuticals: Employment. Yang:Ionis Pharmaceuticals: Employment. O'Dea:Akcea Therapeutics: Employment. Karwatowska-Prokopczuk:Akcea Therapeutics: Employment. Schneider:Ionis Pharmaceuticals: Employment. Geary:Ionis Pharmaceuticals: Employment. Monia:Ionis Pharmaceuticals: Employment.

BACKGROUND: The aim of the study was to compare bone mineral density (BMD) before insertion and at 18 months of use of etonorgestrel- and levonorgestrel-releasing contraceptive implants. METHODS: One hundred and eleven women, 19–43 years of age, were randomly allocated to two groups: 56 to etonorgestrel and 55 to levonorgestrel. BMD was evaluated at the midshaft of the ulna and at the distal radius of the non-dominant forearm using dual-energy X-ray absorptiometry before insertion and at 18 months of use. RESULTS: There was no difference in baseline demographic or anthropometric characteristics, or in BMD of users of either model of implant. BMD was significantly lower at 18 months of use at the midshaft of the ulna in both groups of users. However, no difference was found at the distal radius. Multiple linear regression analysis showed that the variables associated with BMD at 18 months of use in both implant groups were baseline BMD, body mass index (BMI) and difference in BMI (0 versus 18 months of use). CONCLUSIONS: Women of 19–43 years of age using either one of the implants showed lower BMD at 18 months of use at the midshaft of the ulna, however, without a difference at the distal radius.

Patients with cancer are at risk for metabolic disorders. The pathophysiologies include organic dysfunction due to systemic dissemination, dysfunction due to anticancer treatment, paraneoplastic metabolic changes due to tumor proliferation mechanisms, and metabolites production. The main metabolic emergencies in cancer patients are the tumor lysis syndrome, hypercalcemia, hyponatremia, and adrenal insufficiency.

Background A common question among health care professionals is how to manage nonvisible strings in users of intrauterine contraceptives (IUCs) at repeat follow-up visits. This study assessed the position of the IUCs in women who consulted repeatedly with nonvisible IUC strings. Study Design The medical records of the clinic were reviewed to identify new acceptors and switchers who had an IUC inserted between 1990 and 2009. All women were identified whose IUC string could not be visualized at the external os of the cervix by the health care professional at any given follow-up visit, even after attempting a standard maneuver of sweeping the strings from the cervical canal using a cervical brush or trying to visualize the strings in the cervical canal using colposcopy. Data were also retrieved on the use of ultrasonography and/or pelvic X-ray to assess IUC position, as well as data from any subsequent visits at which the IUC strings were nonvisible. Results The medical charts of 14,935 patients using an IUC were reviewed, and 750 women (5.0%) presenting for the first time with missing IUC strings at any follow-up visit were identified. Ultrasound scans showed the IUC to be in situ in 735 cases (98.0%), while 9 women (1.2%) had expelled the device and, in 5 cases (0.7%), the device was found in the pelvis following uterine perforation. IUC strings were missing on a second occasion in 297 cases. The device was found to be in situ in 295 cases (99.3%) and had been expelled in 2 (0.7%). At subsequent consultations, (between 1 and 18 years after the first consultation), strings were missing in 113, 55, 19 and 5 cases. In 111 (98.2%), 54 (98.2%), 18 (94.7%) and 5 (100%) of these cases, respectively, the IUC was found to be in situ, while in the remaining cases, the device had been expelled. Conclusions Missing IUC strings are an uncommon finding, and ultrasonography confirmed that the device was in situ in the majority of these cases. For women with persistent missing IUC strings after one ultrasound scan that has verified appropriate intrauterine position, given the 2.4% likelihood that expulsion may have occurred at the time of subsequent visits, repeating the ultrasound (if available) should be considered for at least one (and possibly two) additional women's visit.

Orientador: Luis Guillermo Bahamondes Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas Resumo: O objetivo do estudo foi avaliar e comparar a densidade mineral óssea (DMO) em mulheres aos 18 meses de uso de implantes contraceptivos liberadores de etonogestrel ou levonorgestrel. Foram admitidas 111 mulheres, de 19 a 43 anos de idade, sendo 56 usuárias do implante liberador de etonogestrel (Implanon®) e 55 mulheres usuárias do implante liberador de levonorgestrel (Jadelle®). A DMO foi avaliada nas porções distal e ultradistal do rádio do antebraço não dominante, usando-se a técnica de absorciometria dupla (DXA), antes da inserção e aos 18 meses de uso. Não houve diferença nas características demográficas ou antropométricas, ou na DMO previamente à inserção de ambos os modelos de implantes. A DMO foi significativamente menor aos 18 meses de uso na região distal do rádio nos dois grupos de usuárias. Entretanto, não houve diferença na região ultradistal. A análise por regressão linear múltipla mostrou que as variáveis associadas com a diminuição da DMO aos 18 meses de uso em ambos os grupos de implantes foram a DMO inicial, índice de massa corporal (IMC) e diferença no IMC (zero versus 18 meses de uso). Mulheres de 19 a 43 anos de idade, usando um ou outro implante, tiveram significativamente menor DMO aos 18 meses de uso na região distal; entretanto sem diferença na região ultradistal do rádio, quando comparada com os valores obtidos antes da inserção Abstract: The objetive of this study was to compare bone mineral density (BMD) before insertion and at 18 months of use of etonogestrel (Implanon®) and levonorgestrel-releasing (Jadelle®) contraceptive implants. One-hundred eleven women, 19-43 years of age, were randomly allocated to 2 groups: 56 to Implanon and 55 to Jadelle. BMD was evaluated at the midshaft of the ulna and at the distal radius of the non-dominant forearm using dual energy X-ray absorptiometry before insertion and at 18 months of use. There was no difference in baseline demographic or anthropometric characteristics, or in BMD of users of either model of implant. BMD was significantly lower at 18 months of use at the midshaft of the ulna in both groups of users. However, no difference was found at the distal radius. Multiple linear regression analysis showed that the variables associated with BMD at 18 months of use in both implant groups were baseline BMD and body mass index (BMI) and difference in BMI (O versus 18 months of use). Women of 19-43 years of age using either one of the implants showed lower BMD at 18 months of use at the midshaft of the ulna, however, without a difference at the distal radius Mestrado Ciências Biomédicas Mestre em Tocoginecologia

To evaluate the prevalence of enlarged ovarian follicles among users of a 20 micrograms/d levonorgestrel-releasing intrauterine system (Mirena, Leiras Oy, Turku, Finland), of subdermal contraceptive implants releasing Nestorone (Population Council, New York, New York) and of the TCu 380A intrauterine device.A cohort study was conducted at the Universidade Estadual de Campinas, Brazil. Three hundred women were enrolled, with 100 participants in each group. Bimanual pelvic examination and vaginal ultrasound were performed during routine gynecologic examinations in women without complaints. In women with enlarged ovarian follicles (or = 25 mm), estradiol and progesterone levels were assessed weekly until disappearance or reduction of the ovarian image.Enlarged ovarian follicles were detected in 19%, 10% and 5% of users of the levonorgestrel system, implants and intrauterine device, respectively. Most of the enlarged ovarian images disappeared after 2 weeks of follow-up. Progesterone levels showed that the intrauterine system and TCu 380A IUD (FEI, North Tonawanda, New York) users had presumably ovulated before the first ultrasound examination in contrast to the implant users.Physicians and users should be aware that findings of enlarged ovarian follicles during the use of progestin-only contraceptives are transient and that no medical interventions are necessary.

Background The aim of this study was to evaluate bone mineral density (BMD) at baseline and at 18 and 36 months of use of etonogestrel (ENG)-and levonorgestrel (LNG)-releasing contraceptive implants. This is a continuation of a previous study in which BMD was evaluated at baseline and at 18 months of use. Methods A total of 111 women, 19–43 years of age, wererandomly allocated to use one of the two implants. At 36 months of follow-up, only 36 and 39 women were still using the ENG- and LNG-releasing implants, respectively. BMD was evaluated at the distal and at the ultra-distal radius of the non-dominant forearm using dual-energy X-ray absorptiometry. Results There was no difference in the BMD of users of either implant at 18 and at 36 months. BMD was significantly lower at 18 and at 36 months at the distal radius in both groups of users compared to pre-insertion values; however, no difference was found at the ultra-distal radius. Conclusion Women 19–43 years of age using either one of these two contraceptive implants for 36 months had lower BMD values at the distal radius compared to pre-insertion values; however, no difference was found at the ultra-distal radius.