Variants in CLDN5 cause a syndrome characterized by seizures, microcephaly and brain calcifications.

The blood-brain barrier ensures CNS homeostasis and protection from injury. Claudin-5 (CLDN5), an important component of tight junctions, is critical for the integrity of the blood-brain barrier. We have identified de novo heterozygous missense variants in CLDN5 in 15 unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications. All variants clustered in one subregion/domain of the CLDN5 gene and the recurrent variants demonstrate genotype-phenotype correlations. We modelled both patient variants and loss of function alleles in the zebrafish to show that the variants analogous to those in patients probably result in a novel aberrant function in CLDN5. In total, human patient and zebrafish data provide parallel evidence that pathogenic sequence variants in CLDN5 cause a novel neurodevelopmental disorder involving disruption of the blood-brain barrier and impaired neuronal function.

De Novo Variants in MAPK8IP3 Cause Intellectual Disability with Variable Brain Anomalies.

Using exome sequencing, we have identified de novo variants in MAPK8IP3 in 13 unrelated individuals presenting with an overlapping phenotype of mild to severe intellectual disability. The de novo variants comprise six missense variants, three of which are recurrent, and three truncating variants. Brain anomalies such as perisylvian polymicrogyria, cerebral or cerebellar atrophy, and hypoplasia of the corpus callosum were consistent among individuals harboring recurrent de novo missense variants. MAPK8IP3 has been shown to be involved in the retrograde axonal-transport machinery, but many of its specific functions are yet to be elucidated. Using the CRISPR-Cas9 system to target six conserved amino acid positions in Caenorhabditis elegans, we found that two of the six investigated human alterations led to a significantly elevated density of axonal lysosomes, and five variants were associated with adverse locomotion. Reverse-engineering normalized the observed adverse effects back to wild-type levels. Combining genetic, phenotypic, and functional findings, as well as the significant enrichment of de novo variants in MAPK8IP3 within our total cohort of 27,232 individuals who underwent exome sequencing, we implicate de novo variants in MAPK8IP3 as a cause of a neurodevelopmental disorder with intellectual disability and variable brain anomalies.

Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathy caused by bi-allelic loss-of-function variants in GAD1, as presented by 11 patients from six independent consanguineous families. Seizure onset occurred in the first 2 months of life in all patients. All 10 patients, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1-/- mouse model. Four patients died before 4 years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the γ-aminobutyric acid (GABA) metabolism as it catalyses the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele.

Isolated Central Nervous System Vasculitis as a Manifestation of Neurosarcoidosis.

A 62-year-old male presented to our clinic with recurrent fever, skin lesions (petechiae), scleral wounds, and hilar adenomegaly. A diagnosis of sarcoidosis was established, which resolved with corticosteroid treatment. After a few months, the patient developed confusion and behavioral changes, with few objective neurological deficits. Brain magnetic resonance imaging showed slight focal meningeal enhancement (prepontine region). The level of angiotensin-converting enzymes was normal in the serum and increased in the cerebrospinal fluid. The patient was diagnosed with neurosarcoidosis, and corticosteroid treatment was prescribed, yielding good clinical response. Nine months later, the patient presented with multiple ischemic strokes, and arteriography demonstrated multiple distal irregularities in all arterial territories, suggesting cerebral vasculitis. Even with corticosteroids, cyclophosphamide, and intravenous immunoglobulin, the patient died. Vasculitis is rarely seen in association with sarcoidosis, and in this case, no systemic manifestation was observed at the time that the patient developed vasculitis.

Medication-overuse headache-a review of different treatment strategies.

Medication-overuse headache (MOH) can develop from primary headaches. MOH is usually the result of overuse of symptomatic medications. It is a noteworthy personal and societal burden. The identification and treatment of patients at risk for MOH is an essential component of MOH management. Medication overuse can be modifiable and can advance from episodic to chronic migraine. Treatment for MOH is complex, and experts in the field have varied views on the most appropriate strategy for MOH treatment. The objective of this review is to give a comprehensive synopsis of the literature for the management of MOH. Treatment strategies, such as detoxification and prevention, are the debatable issues. Medication withdrawal is the foundation for management. The available literature suggested abrupt withdrawal with preventive approaches for early management. Bridging therapy could be useful to get relief from withdrawal symptoms. Multidisciplinary choices proved beneficial in supporting withdrawal and preventing relapse. Worldwide, the termination of overused medications has been observed as a standard treatment strategy; however, patient-specific approaches should be taken.

GIGYF1 disruption associates with autism and impaired IGF-1R signaling.

Autism spectrum disorder (ASD) represents a group of neurodevelopmental phenotypes with a strong genetic component. An excess of likely gene-disruptive (LGD) mutations in GIGYF1 was implicated in ASD. Here, we report that GIGYF1 is the second-most mutated gene among known ASD high-confidence risk genes. We investigated the inheritance of 46 GIGYF1 LGD variants, including the highly recurrent mutation c.333del:p.L111Rfs*234. Inherited GIGYF1 heterozygous LGD variants were 1.8 times more common than de novo mutations. Among individuals with ASD, cognitive impairments were less likely in those with GIGYF1 LGD variants relative to those with other high-confidence gene mutations. Using a Gigyf1 conditional KO mouse model, we showed that haploinsufficiency in the developing brain led to social impairments without significant cognitive impairments. In contrast, homozygous mice showed more severe social disability as well as cognitive impairments. Gigyf1 deficiency in mice led to a reduction in the number of upper-layer cortical neurons, accompanied by a decrease in proliferation and increase in differentiation of neural progenitor cells. We showed that GIGYF1 regulated the recycling of IGF-1R to the cell surface. KO of GIGYF1 led to a decreased level of IGF-1R on the cell surface, disrupting the IGF-1R/ERK signaling pathway. In summary, our findings show that GIGYF1 is a regulator of IGF-1R recycling. Haploinsufficiency of GIGYF1 was associated with autistic behavior, likely through interference with IGF-1R/ERK signaling pathway.

Loss of FOCAD, operating via the SKI messenger RNA surveillance pathway, causes a pediatric syndrome with liver cirrhosis.

Cirrhosis is usually a late-onset and life-threatening disease characterized by fibrotic scarring and inflammation that disrupts liver architecture and function. While it is typically the result of alcoholism or hepatitis viral infection in adults, its etiology in infants is much less understood. In this study, we report 14 children from ten unrelated families presenting with a syndromic form of pediatric liver cirrhosis. By genome/exome sequencing, we found recessive variants in FOCAD segregating with the disease. Zebrafish lacking focad phenocopied the human disease, revealing a signature of altered messenger RNA (mRNA) degradation processes in the liver. Using patient's primary cells and CRISPR-Cas9-mediated inactivation in human hepatic cell lines, we found that FOCAD deficiency compromises the SKI mRNA surveillance pathway by reducing the levels of the RNA helicase SKIC2 and its cofactor SKIC3. FOCAD knockout hepatocytes exhibited lowered albumin expression and signs of persistent injury accompanied by CCL2 overproduction. Our results reveal the importance of FOCAD in maintaining liver homeostasis and disclose a possible therapeutic intervention point via inhibition of the CCL2/CCR2 signaling axis.

MECP2-related conditions in males: A systematic literature review and 8 additional cases.

OBJECTIVE: To present a cohort of 8 males and perform a systematic review of all published cases with a single copy of MECP2 carrying a pathogenic variant. METHODS: We reviewed medical records of males with a single copy of MECP2 carrying a pathogenic variant. We searched in Medline (Pubmed) and Embase to collect all articles which included well-characterized males with a single copy of MECP2 carrying a pathogenic or likely pathogenic variant in MECP2 (1999-2020). RESULTS: The literature search yielded a total of 3,185 publications, of which 58 were included in our systematic review. We were able to collect information on 27 published patients with severe neonatal encephalopathy, 47 individuals with isolated or familial mental retardation X-linked 13 (XLMR13), as well as 24 individuals with isolated or familial Pyramidal signs, parkinsonism, and macroorchidism (PPM-X). In our cohort, we met eight individuals aged 4 to 19-year-old at the last evaluation. Three MECP2-associated phenotypes were seen in male carriers of a single copy of the gene: severe neonatal encephalopathy (n = 5); X-linked intellectual deficiency 13 (n = 2); and pyramidal signs, parkinsonism, and macroorchidism (PPM-X) (n = 1). Two novel de novo variants [p.(Gly252Argfs∗7) and p.(Tyr132Cys)] were detected. CONCLUSION: In males, the MECP2 pathogenic variants can be associated with different phenotypes, including neonatal severe encephalopathy, intellectual deficiency, or late-onset parkinsonism and spasticity. The typical RS phenotype is not expected in males, except in those with Klinefelter syndrome or somatic mosaicism for MECP2.

Additional observation of a de novo pathogenic variant in KCNT2 leading to epileptic encephalopathy with clinical features of frontal lobe epilepsy.

INTRODUCTION: KCNT2 was recently recognized as a gene associated with neurodevelopmental disorder and epilepsy. CASE REPORT: We present an additional observation of a 16-year-old male patient with a novel de novo KCNT2 likely pathogenic variant and review the five previously reported cases of de novo variants in this gene. DISCUSSION: Whole exome sequencing identified the missense variant c.725C > A p.(Thr242Asn), which was confirmed by Sanger sequencing. Our patient has a refractory stereotyped and monomorphic type of hyperkinetic focal motor seizure, similar to what is seen in frontal lobe epilepsy, occurring only during sleep. This type of seizure is not usually seen in epileptic encephalopathies.

ATP6V1B2-related epileptic encephalopathy.

ATP6V1B2 encodes a subunit of the lysosomal transmembrane proton pump necessary for adequate functioning of several acid hydrolases. De novo monoallelic variants of this gene have been associated with two distinct phenotypes: Zimmermann-Laband syndrome 2 (ZLS2), an intellectual deficiency/multiple malformation syndrome, and dominant deafness onychodystrophy (DDOD), a multiple malformation syndrome without cognitive involvement. Epilepsy is not observed in DDOD, is variably present in ZLS2, but is a common feature in Zimmermann-Laband syndrome 1 (ZLS1) (caused by monoallelic pathogenic variants in KCNH1) and Zimmermann-Laband syndrome-like (ZLSL) (associated with KCNK4 variants). Herein, we report a case of an infant with severe epileptic encephalopathy with microcephaly and profound developmental delay, associated with a novel de novo loss-of-function variant in ATP6V1B2, diagnosed by whole-exome sequencing. This finding expands the spectrum of ATP6V1B2-associated disorders and adds ATP6V1B2 as a new member for the growing list of early-onset epileptic encephalopathy genes. [Published with video sequence].

Application of Whole-Exome Sequencing in Detecting Copy Number Variants in Patients with Developmental Delay and/or Multiple Congenital Malformations.

Overcoming challenges for the unambiguous detection of copy number variations is essential to broaden our understanding of the role of genomic variants in the clinical phenotype. With the improvement of software and databases, whole-exome sequencing quickly can become an excellent strategy in the routine diagnosis of patients with a developmental delay and/or multiple congenital malformations. However, even after a detailed analysis of pathogenic single-nucleotide variants and indels in known disease genes, using whole-exome sequencing, some patients with suspected syndromic conditions are left without a conclusive diagnosis. These negative results could be the result of different factors including nongenetic etiologies, lack of knowledge about the genes that cause different disease phenotypes, or, in some cases, a deletion or duplication of genomic information not routinely detectable by whole-exome sequencing variant calling. Although copy number variant detection is possible using whole-exome sequencing data, such analysis presents significant challenges and cannot yet be used to replace chromosomal arrays for identification of deletions or duplications.

Heterozygous loss of function of NR4A2 is associated with intellectual deficiency, rolandic epilepsy, and language impairment.

Recognition of a de novo mutation in NR4A2 associated with a neurodevelopmental phenotype reinforces its role in 2q23q24 microdeletion syndrome. Using the proband WES data and the probability of loss-of-function intolerance index (pLi) set at 1.0 (highest intolerance constraint), we could target NR4A2 as the candidate gene in this patient.

Impact of mammography screening on thetreatment of women diagnosed with breast cancer

Objective: To evaluate the influence of mammographic screening on the treatment of women with previous diagnosis of breast cancer. Method: Cross-sectional, descriptive, observational study, with primary and secondary data collection and quantitative approach. It was performed in a high complexity hospital in the South region of Santa Catarina, Brazil, where patients with previous history of breast cancer were evaluated during the period from 2012 to 2017, and who were undergoing oncological follow-up at the same hospital. The variables were expressed as frequency and percentage. Inferential statistical analyses were performed with a significance level of alpha = 0.05 and, therefore, 95% confidence interval. Therefore, the confidence interval was 95%. Associations between variables were investigated using the Pearson's χ² and the likelihood ratio tests. Results: Among the 99 analyzed patients, 58.6% annually performed the examination and 49.5% had elapsed less than 12 months between the last performed mammogram and the diagnosis. There was a higher frequency of stage I disease, corroborating the results that 74.7% of patients underwent breastconserving surgeries and 68.7% underwent sentinel lymph node biopsy, rather than extensive surgeries. Regarding the treatment of choice, patients with annual or biennial mammographic frequency had similar surgical and chemotherapeutic outcomes in relation to patients who had a mammogram without defined frequency or who had never undergone it. Conclusion: Patients who underwent mammography on an annual frequency and those whose time between the last mammogram and the diagnosis of cancer was less than 12 months had tumors of lesser extent at diagnosis; however, it did not influence the type of treatment chosen.

Níveis de vitamina D em mulheres climatéricas no sul do Brasil / Vitamin D levels in climacteric women in southern Brazil

Sendo a hipovitaminose D um tema de extrema importância e evidência atualmente, nós dosamos os níveis séricos de vitamina D em pacientes no climatério para conhecer a prevalência de deficiência desta vitamina em diferentes períodos do ano. Foram coletados dados demográficos, de exposição solar e vitamina D sérica de 43 pacientes climatéricas com idade entre 40 e 65 anos, em dois períodos do ano: junho, julho e agosto de 2013 (grupo I) e março abril e maio de 2014 (grupo II). Das pacientes estudadas, 16% apresentaram deficiência (<20 ng/ml) e 34% insuficiência (entre 20 e 29 ng/mml). Não houve diferença estatística entre os grupos avaliados quanto às características demográficas, de exposição solar e quanto aos outros resultados laboratoriais. O nível médio de Vitamina D sérica no grupo I foi 26,46 ng/ml e no grupo II foi 31,64 ng/ml (p 0,05). A prevalência de deficiência foi maior no grupo I (p<0,001). O nosso estudo foi realizado em Florianópolis, cidade litorânea, que tem latitude 27º S e apesar de não ser uma latitude tão alta, também encontramos altas taxas de deficiência e insuficiência de vitamina D, sendo que as taxas de deficiência foram significativamente maiores nos meses mais frios (p<0,001). Os níveis médios de vitamina D também foram menores no inverno (p 0,05).

Since hypovitaminosis D is a currently important subject, we measure the levels of vitamin D in climacteric patients to know the prevalence of vitamin D deficiency in different seasons. We collect demographic information, as well as sun exposure habits and serum levels of vitamin D from 43 climacteric patients with 40-65 years old in two different periods: june, july and august of 2013 (group I), and march, april and may of 2014 (group II). Sixteen percent of the patients included in the study present vitamin D deficiency (< 20ng/ml) and 34% insufficiency (20-29 ng/ml). There was no statistic difference between the groups with respect to demographic characteristics, sun exposure and the others laboratorial results. The mean level of vitamin D for group I was 26,46ng/ml e for group II was 31,64 ng/ml (p 0,05). The deficiency´s prevalence was higher in group I (p<0,001). Our study was performed in Florianópolis, a seaside city, 27°S latitude. Despite the localization, we found high rates of deficiency and insufficiency of vitamin D. The deficiency rates was significantly higher in the winter months (p< 0,001). The mean levels of vitamin D was lower in winter (p 0,05).

Reações dos familiares frente à descoberta da deficiência dos filhos / Reactions and feelings of families towards the discovery of the disability of their children

The birth of an impaired child is of great impact to the family, causing changes in the family dynamics. Different feelings and reactions are experienced uniquely by each family member. The lack of preparation of health professionals to deal with this delicate time of diagnosis might exacerbate feelings, complicating the acceptance of the child and the search for treatment. Based on these considerations, the present study aimed to investigate the reactions and feelings that permeate and pervade the lives of parents of impaired children, trying to contribute to the practice of occupational therapists and other professionals. The study was conducted with parents of children aged between two and seven years old who presented disabilities in which motor function was the most affected item. Four mothers and three fathers of different ages participated in the study. Semi-structured interviews were conducted based on a questionnaire prepared by the researchers. The results showed the emotional fragility of parents toward the matter and the lack of preparation of health professionals at the time of diagnosis. In general, shock, negation, guilt, and sadness appeared as the most common feelings and reactions when participants are impacted by the diagnosis. Knowing that the parental role is very important for child development, occupational therapy can develop an important work with families of impaired children.

O nascimento de uma criança deficiente é algo de grande impacto para a família, provocando mudanças na dinâmica familiar. Diversos sentimentos e reações são vividos de forma única por cada membro. A falta de preparo dos profissionais de saúde para lidar com esse momento delicado de diagnóstico pode vir a agravar os sentimentos, dificultando a aceitação do filho e a busca por tratamento. Com base nessas considerações, o presente estudo teve por objetivo investigar, junto aos pais de crianças com deficiência, as reações e sentimentos que permearam e permeiam sua vida, buscando, assim, contribuir para a prática de terapeutas ocupacionais e outros profissionais da área. O estudo foi realizado com pais de crianças com idade entre dois e sete anos que apresentassem deficiências nas quais o quesito motor se mostrava o mais afetado. Participaram quatro mães e três pais de diferentes faixas etárias. Foram realizadas entrevistas semiestruturadas com base em questionário elaborado pelas investigadoras. Os resultados demonstraram fragilidade emocional dos pais frente ao assunto e falta de preparo dos profissionais da área da saúde no momento do diagnóstico. De forma geral, choque, negação, culpa e tristeza apareceram como os sentimentos e reações mais comuns quando os participantes são impactados pela noticia desse diagnóstico. Sabendo que é de suma importância o papel dos pais no desenvolvimento de seus filhos, a terapia ocupacional pode vir a atuar também junto à família das crianças com deficiência.

Marcadores clínicos e laboratoriais para doença hipertensiva específica da gravidez / Clinical and laboratory markers for preeclampsia pregnancy

A doença hipertensiva específica da gravidez (DHEG)é uma patologia prevalente e de etiologia desconhecidaque tem grande impacto na morbimortalidade materno--fetal, dessa forma o objetivo deste trabalho foi avaliarqual o melhor marcador clínico e laboratorial para predizero desenvolvimento da DHEG. Foi realizado análisede prontuário de 57 pacientes com risco aumentadopara a doença, atendidas no Centro de Gestação de AltoRisco de Itajaí ? CRESCEM, analisando os marcadoresclínicos ? idade, paridade, história mórbida pregressa,índice de massa corpórea (IMC), história da doença atual? e marcadores laboratoriais ? colesterol total, HDL,LDL, triglicerídeos, proteína C reativa, cálcio sérico, fatorantinucléico, KPTT, anticorpo anticardiolipina IgG eIgM, hormônio tireoestimulante e dopplerfluxometriadas artérias uterinas. Os resultados obtidos foram: omais sensível para detecção de DHEG foi a anticardiolipinaIgM que apresentou sensibilidade de 66,6%, comespecificidade igualmente elevada de 64%. Os valorespreditivos positivo e negativos foram respectivamente,9 e 94%. O parâmetro que se mostrou mais específicofoi o IMC elevado com 79% de especificidade, 46% desensibilidade, 73% de preditividade positiva e 54% depreditividade negativa. O elemento com o maior valorpreditivo positivo foi o cálcio sérico com valor de 90%e preditividade negativa de 15%. Sua especificidadefoi de 71% e sensibilidade 39%. Os autores concluíramque dentre todos os marcadores analisados a anticardiolipinaIgM é o mais indicado para screening depré-eclampsia, porém estudos com amostra estendida,faz-se necessário.

The hypertensive disorders of pregnancy (HDP) is aprevalent disease of unknown etiology that has greatimpact on morbidity and mortality and fetal outcome,therefore the purpose was to determine the best clinicaland laboratory marker to predict the development ofpreeclampsia. The research was conducted by analyzing57 medical reports from patients?s with increased riskfor this disease, attended at Center for High-Risk PregnancyItajaí - CRESCEM, analyzing the clinical markers- age, parity, previous disease history, body mass index,history of present illness - and laboratory markers - totalcholesterol, HDL, LDL, triglycerides, C-reactive protein,serum calcium, antinuclear antibodies, KPTT, anticardiolipinantibody IgG and IgM antibodies, thyroid-stimulatinghormone and uterine artery Doppler. The resultsshowed that the most sensitive test for detectionof preeclampsia was the anticardiolipinIgM which hada sensitivity of 66.6%, with equally high specificity64%. The negative and positive predictive values wererespectively 9 and 94%. The most specific parameterwas BMI wich presented79% specificity, 46% sensitivity,73% positive predictivity and negative predictivity54%.Serum calcium revealed to have the highest positivepredictive value, 90% and negative predictivityvalue of 15%, while its specificity was 71% and sensitivityof 39%. The authors concluded that among allthe markers analyzed the anticardiolipinIgM is the mostsuitable for screening of pre-eclampsia,but studies withextended samples, are necessary.

Perfil epidemiológico das mortes maternas em Itajaí no período de 1997-2007 / Epidemiologic profile of maternal mortality in Itajai from 1997 to 2007

Introdução: A morte materna está entre as 10 principaiscausas de óbitos de mulheres em idade fértil naAmérica Latina e Brasil. Dados epidemiológicos apontamíndices e tendências da mortalidade materna, permitindoa análise de diversas variáveis diretamenterelacionadas com fatores causais evitáveis. Objetivo:Descrever o perfil epidemiológico das mortes maternasdas residentes em Itajaí no período de 1997-2007.Material e Métodos: Estudo epidemiológico, descritivo.Através de dados processados pela Secretaria da Saúde,a amostra foi de 25 óbitos maternos. Participaramda amostra mulheres de 10 a 49 anos, que na ocasiãodo óbito estavam grávidas, parturientes ou que estiveramgrávidas nos últimos 12 meses. O coeficiente demortalidade materna foi calculado através da relaçãoentre o número de óbitos maternos e o total de nascidosvivos. Resultados e Discussão: A Razão de MortalidadeMaterna (RMM) média nos últimos 11 anos foi90,47 óbitos/100.000 nascidos vivos, mostrando-semaior do que a média nacional. A análise da série históricamostra oscilações irregulares com um aumentocontínuo e progressivo nos últimos 4 anos, culminandocom um expressivo aumento em 2007. Pôde-seobservar que 40% dos óbitos ocorreram no puerpérioimediato por complicações infecciosas. A maiorprevalência das mortes situou-se entre 30 e 39 anos.Houve maior prevalência de óbitos maternos (44%)em mulheres com baixa escolaridade. A maioria daspacientes teve número de consultas pré-natais insuficientes(52%). Quanto ao tipo de parto, 44% foramsubmetidas à cesariana. Conclusão: A RMM sofreu oscilaçõesno período de 1997 a 2007, com tendênciaa um aumento significativo neste último ano. O perfilepidemiológico não difere daquelas com maior riscode óbito segundo a literatura: baixa escolaridade, faixaetária, parto por cesariana e pré-natal inadequado.O preenchimento incorreto das declarações de óbitolimitou conclusões, principalmente das causas de óbitos,que poderiam elucidar fatores causais importantespara estratégias de melhora na assistência à saúde dasmulheres de Itajaí.

Introduction: The maternal mortality is among the 10leading causes of death during reproductive age in themajority of the countries of Latin America. Epidemiologicaldata indicates rates and trends of maternal mortality,allowing the analysis of several variables directly relatedto preventable factors. Objective: To describe theepidemiological profile of maternal mortality in Itajaífrom 1997 to 2007. Methods: This is an epidemiological,descriptive study. The data was collected from ItajaíPublic Health Authorities database. The sample includedwomen aged among 10 and 49 years, that in the occasionof the death were pregnant, parturient or that hadbeen pregnant in the last 12 months, reaching a totalof 25 maternal deaths. The maternal mortality rate wascalculated according to the relation between the numberof deaths and total live-births in the same area andperiod. The statistical analysis was calculated by relativefrequency of the variables. Results: Maternal mortalityrate in the last 11 years was 90.47 maternal deaths per100.000 live-births. After considering the correctionfactor for maternal deaths (2.04), the maternal mortalityrate was adjusted to 184.55, being higher than the Braziliannational rate. The historical series analysis shows irregularoscillations in this period, with a continuous andgradual increase for the last 4 years, culminating withthe highest mark in 2007. It was observed that 40% ofthe deaths had occurred in the immediate puerperal period,probably linked to hemorrhagic complications. Regardingmaternal age, the higher prevalence was placedbetween 30 and 39 years of age, totalizing 48%, whatis not in concordance with the consulted literature?sdata. When instruction degree and deaths distributionwas analyzed, it was observed that the highest prevalenceof maternal death was among women who had 4to 7 years of studies, representing 44% of the total. Themajority of patients had insufficient number of prenatalvisits (52%). Regarding the mode of delivery, 44% werec-sections. Conclusion: The maternal mortality rate inItajai had irregular oscillations between 1997 and 2007with a significant increase in this last year. The epidemiologicalprofile of the patients does not differ fromthose with higher risk of death according to the literature.The incomplete data of Obituary Registry, the officialsource of data on deaths, limited this research and conclusions,which would have been important to detectcause factors, with the aim of improving public women?shealth care in this city.

Avaliação dos fatores hormonais em mulheres com diagnóstico de neoplasia de mama com idade superior a 40 anos / Evaluation of hormonal factors in women diagnosed with breast neoplasia at age superior than 40 years

Introdução: O câncer de mama apresenta elevada incidência e mortalidade em todo o mundo, representando um grave problema de saúde pública. Ele é o segundo tipo de câncer mais frequente no mundo e o mais frequente entre as mulheres. Objetivo: Compreender como os fatores de risco hormonais podem influenciar no desenvolvimento de câncer de mama em mulheres com idade superior a 40 anos. Materiais e métodos: Estudo retrospectivo e transversal através da revisão de prontuários de pacientes com idade superior a 40 anos e portadoras de câncer de mama, atendidas no ambulatório de mastologia da Universidade do Vale do Itajaí (UNIVALI), em Itajaí (SC), de janeiro de 2003 até março de 2009; 484 pacientes foram incluídas no estudo. Foi analisada a relação de cada fator hormonal estudado em cada faixa etária. Os dados foram analisados através do teste de t e por regressão logística. Consideramos um nível de significância estatística de 0,05. Resultados: A menarca precoce confirmou-se como fator de risco para o aparecimento precoce do câncer de mama assim como o uso de contraceptivo oral hormonal, ambos com p<0,05. Ausência de aleitamento , abortamento, idade da menopausa e uso de terapia hormonal não foram fatores com significância estatística para o desenvolvimento de câncer de mama. Observou-se que o número elevado de gestações confirma-se como fator protetor. Conclusão: Uma vez que não sabemos quais os exatos fatores de risco para o desenvolvimento de neoplasia mamária, sugerimos que o screening para câncer de mama seja modificado e individualizado no sentido de intervir de maneira mais eficiente.

Background: Breast cancer presents high incidence and mortality all over the world, representing an important problem for public health. It is the second most common type of cancer in the world and the commonest malignancy in women. Objective: Understand how hormonal risk factors influence the breast cancer development in women with age higher than 40 years. Methods: retrospective and transversal study through charts review of patients aged over 40 years, diagnosed with breast cancer, in mastology service of University of Vale do Itajaí (UNIVALI), Itajaí (SC) from January 2003 until March 2009. We found 484 patients. We analized the relationship of each hormonal factor with age estratified by decades. The data were analized through t test and logistic regression. We consider a statistical significance level of 0.05. Results: Early menarche and hormonal contraceptive were confirmed as risk factors for breast cancer (p<0,05). Lack of breastfeeding, abortion, menopause age and hormonal therapy were not significanthy statistical for breast cancer diagnosis. The high number of pregnancies persists as a protective factor. Conclusions: Once we don?t know exactly wich risk factors act in the development of breast cancer, we sugest to modify and individualize the screening for breast cancer, so we can interact in a efficiently way.