RESUMO
BACKGROUND: Information on cause of death may help appraise the degree to which the high excess mortality after hip fracture reflects pre-existing comorbidities or the injury itself. We aimed to describe causes of death and cause-specific excess mortality through the first year after hip fracture. METHODS: For studying the distribution of causes of death by time after hip fracture, we calculated age-adjusted cause-specific mortality at 1, 3, 6 and 12 months in patients hospitalized with hip fracture in Norway 1999-2016. Underlying causes of death were obtained from the Norwegian Cause of Death Registry and grouped by the European Shortlist for Causes of Death. For estimating excess mortality, we performed flexible parametric survival analyses comparing mortality hazard in patients with hip fracture (2002-2017) with that of age- and sex matched controls drawn from the Population and Housing Census 2001. RESULTS: Of 146,132 Norwegians with a first hip fracture, a total of 35,498 (24.3%) died within one year. By 30 days post-fracture, external causes (mainly the fall causing the fracture) were the underlying cause for 53.8% of deaths, followed by circulatory diseases (19.8%), neoplasms (9.4%), respiratory diseases (5.7%), mental and behavioural disorders (2.0%) and diseases of the nervous system (1.3%). By one-year post-fracture, external causes and circulatory diseases together accounted for approximately half of deaths (26.1% and 27.0%, respectively). In the period 2002-2017, cause-specific one-year relative mortality hazard in hip fracture patients vs. population controls ranged from 1.5 for circulatory diseases to 2.5 for diseases of the nervous system in women, and correspondingly, from 2.4 to 5.3 in men. CONCLUSIONS: Hip fractures entail high excess mortality from all major causes of death. However, the traumatic injury of a hip fracture is the most frequently reported underlying cause of death among older patients who survive less than one year after their fracture.
Assuntos
Doenças Cardiovasculares , Fraturas do Quadril , Osteoporose , Masculino , Humanos , Feminino , Noruega/epidemiologia , Fraturas do Quadril/epidemiologia , Osteoporose/epidemiologia , Comorbidade , Fatores de Risco , Doenças Cardiovasculares/epidemiologiaRESUMO
BACKGROUND: Reliable statistics on the underlying cause of death are essential for monitoring the health in a population. When there is insufficient information to identify the true underlying cause of death, the death will be classified using less informative codes, garbage codes. If many deaths are assigned a garbage code, the information value of the cause-of-death statistics is reduced. The aim of this study was to analyse the use of garbage codes in the Norwegian Cause of Death Registry (NCoDR). METHODS: Data from NCoDR on all deaths among Norwegian residents in the years 1996-2019 were used to describe the occurrence of garbage codes. We used logistic regression analyses to identify determinants for the use of garbage codes. Possible explanatory factors were year of death, sex, age of death, place of death and whether an autopsy was performed. RESULTS: A total of 29.0% (290,469/1,000,128) of the deaths were coded with a garbage code; 14.1% (140,804/1,000,128) with a major and 15.0% (149,665/1,000,128) with a minor garbage code. The five most common major garbage codes overall were ICD-10 codes I50 (heart failure), R96 (sudden death), R54 (senility), X59 (exposure to unspecified factor), and A41 (other sepsis). The most prevalent minor garbage codes were I64 (unspecified stroke), J18 (unspecified pneumonia), C80 (malignant neoplasm with unknown primary site), E14 (unspecified diabetes mellitus), and I69 (sequelae of cerebrovascular disease). The most important determinants for the use of garbage codes were the age of the deceased (OR 17.4 for age ≥ 90 vs age < 1) and death outside hospital (OR 2.08 for unknown place of death vs hospital). CONCLUSION: Over a 24-year period, garbage codes were used in 29.0% of all deaths. The most important determinants of a death to be assigned a garbage code were advanced age and place of death outside hospital. Knowledge of the national epidemiological situation, as well as the rules and guidelines for mortality coding, is essential for understanding the prevalence and distribution of garbage codes, in order to rely on vital statistics.
Assuntos
Classificação Internacional de Doenças , Autopsia , Causas de Morte , Progressão da Doença , Humanos , Sistema de RegistrosRESUMO
INTRODUCTION: Falls in older aged adults are an important public health problem. Insight into differences in fall-related injury rates between countries can serve as important input for identifying and evaluating prevention strategies. The objectives of this study were to compare Global Burden of Disease (GBD) 2017 estimates on incidence, mortality and disability-adjusted life years (DALYs) due to fall-related injury in older adults across 22 countries in the Western European region and to examine changes over a 28-year period. METHODS: We performed a secondary database descriptive study using the GBD 2017 results on age-standardised fall-related injury in older adults aged 70 years and older in 22 countries from 1990 to 2017. RESULTS: In 2017, in the Western European region, 13 840 per 100 000 (uncertainty interval (UI) 11 837-16 113) older adults sought medical treatment for fall-related injury, ranging from 7594 per 100 000 (UI 6326-9032) in Greece to 19 796 per 100 000 (UI 15 536-24 233) in Norway. Since 1990, fall-related injury DALY rates showed little change for the whole region, but patterns varied widely between countries. Some countries (eg, Belgium and Netherlands) have lost their favourable positions due to an increasing fall-related injury burden of disease since 1990. CONCLUSIONS: From 1990 to 2017, there was considerable variation in fall-related injury incidence, mortality, DALY rates and its composites in the 22 countries in the Western European region. It may be useful to assess which fall prevention measures have been taken in countries that showed continuous low or decreasing incidence, death and DALY rates despite ageing of the population.
Assuntos
Acidentes por Quedas , Efeitos Psicossociais da Doença , Saúde Global , Acidentes por Quedas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Europa (Continente) , Carga Global da Doença , Grécia , Humanos , Incidência , Pessoa de Meia-Idade , Países Baixos , Noruega , Anos de Vida Ajustados por Qualidade de VidaRESUMO
BACKGROUND: Falls can lead to severe health loss including death. Past research has shown that falls are an important cause of death and disability worldwide. The Global Burden of Disease Study 2017 (GBD 2017) provides a comprehensive assessment of morbidity and mortality from falls. METHODS: Estimates for mortality, years of life lost (YLLs), incidence, prevalence, years lived with disability (YLDs) and disability-adjusted life years (DALYs) were produced for 195 countries and territories from 1990 to 2017 for all ages using the GBD 2017 framework. Distributions of the bodily injury (eg, hip fracture) were estimated using hospital records. RESULTS: Globally, the age-standardised incidence of falls was 2238 (1990-2532) per 100 000 in 2017, representing a decline of 3.7% (7.4 to 0.3) from 1990 to 2017. Age-standardised prevalence was 5186 (4622-5849) per 100 000 in 2017, representing a decline of 6.5% (7.6 to 5.4) from 1990 to 2017. Age-standardised mortality rate was 9.2 (8.5-9.8) per 100 000 which equated to 695 771 (644 927-741 720) deaths in 2017. Globally, falls resulted in 16 688 088 (15 101 897-17 636 830) YLLs, 19 252 699 (13 725 429-26 140 433) YLDs and 35 940 787 (30 185 695-42 903 289) DALYs across all ages. The most common injury sustained by fall victims is fracture of patella, tibia or fibula, or ankle. Globally, age-specific YLD rates increased with age. CONCLUSIONS: This study shows that the burden of falls is substantial. Investing in further research, fall prevention strategies and access to care is critical.
Assuntos
Acidentes por Quedas , Carga Global da Doença , Saúde Global , Humanos , Incidência , Expectativa de Vida , Morbidade , Prevalência , Anos de Vida Ajustados por Qualidade de VidaRESUMO
BACKGROUND: For injury deaths, the underlying cause of death is defined as the circumstances leading to the injury. When this information is missing, the ICD-10 code X59 (Exposure to unspecified factor) is used. Lack of knowledge of factors causing injuries reduces the value of the cause of death statistics. The aim of this study was to identify predictors of X59-coded deaths in Norway, and to assess methods to identify the true underlying cause of injury deaths. METHODS: We used data from the Norwegian Cause of Death Registry from 2005 to 2014. We used logistic regression to identify determinants of X59-coded deaths. For redistribution of the X59 deaths, we used a multinomial logistic regression model based on the cases where injury circumstances were known. The data were divided into training and test sets. The model was developed on the training set and assessed on the test set before it was applied to the X59 deaths. The models used death certificate information on the nature of injury and demographic characteristics as predictor variables. Furthermore, we mailed a query to the certifying physicians of X59 deaths reported in the year 2015, where we asked for additional information on the circumstances leading to the fatal injury. RESULTS: There were 24,963 injury deaths reported to the Cause of Death Registry of Norway 2005-2014. Of these, 6440 (25.8%) lacked information on the circumstances leading to the death. The strongest predictor for a X59 death was the nature of injury (hip fracture), followed by lack of information on the scene of injury. Applying our redistribution algorithm, we estimated that 97% of the X59-coded deaths were accidental falls. The strongest covariate was the nature of injury, followed by place of death and age at death. In 2015, there were 591 X59-coded deaths. Queries were sent to the certifying doctors in 559 cases. Among the informative replies to the query, 88% of the deaths were reclassified to accidental falls. CONCLUSIONS: A large proportion of injury deaths in Norway lack information on the circumstances leading to the fatal injury. Typically, these deaths represent accidental falls causing hip fracture in elderly individuals.
Assuntos
Atestado de Óbito , Ferimentos e Lesões/mortalidade , Acidentes por Quedas/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Codificação Clínica , Feminino , Lesões do Quadril/mortalidade , Humanos , Classificação Internacional de Doenças , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Sistema de RegistrosRESUMO
OBJECTIVE: Ruptured infrarenal abdominal aortic aneurysms (rAAAs) represent both a life-threatening emergency for the affected patient and a considerable health burden globally. The aim of this study was to investigate the contemporary epidemiology of rAAA in a defined Norwegian population for which both hospital and autopsy data were available. METHODS: This was a retrospective, single-center population-based study of rAAA. The study includes all consecutively diagnosed prehospital and in-hospital cases of rAAA in the catchment area of Stavanger University Hospital between January 2000 and December 2012. Incidence and mortality rates (crude and adjusted) were calculated using national demographic data. RESULTS: A total of 216 patients with primary rAAA were identified. The adjusted incidence rate for the study period was 11.0 per 100,000 per year (95% confidence interval [CI], 9.6-12.5). Twenty patients died out of the hospital, and 144 of the 196 patients (73%) admitted to the hospital underwent surgery. The intervention rate varied from 48% to 81% during the study period. The adjusted mortality rate was 7.5 per 100,000 per year (95% CI, 6.3-8.8). No differences in the incidence and mortality rates were found in comparing early and late periods. The 90-day standardized mortality ratio for the study period was 37.2 (95% CI, 31.6-43.7). The overall 90-day mortality was 68% (146 of 216 persons) and 51% (74 of 144 persons) for the patients treated for rAAA. CONCLUSIONS: We found a stable incidence and mortality rate during a decade. The prehospital death rate was lower (9%), the intervention rate (73%) higher, and the total mortality (68%) lower than in most other studies. Geographic and regional differences may influence the epidemiologic description of rAAA and hence should be taken into consideration in comparing outcomes for in-hospital mortality and intervention rates.
Assuntos
Aneurisma Roto/mortalidade , Aneurisma Roto/cirurgia , Aneurisma da Aorta Abdominal/mortalidade , Aneurisma da Aorta Abdominal/cirurgia , Comparação Transcultural , Idoso , Idoso de 80 Anos ou mais , Feminino , Mortalidade Hospitalar , Hospitais Universitários/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Noruega , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: The increasing incidence of prosthesis revision surgery in the Western world has led to an increased focus on the capacity for stem removal. We previously reported on a femoral stem implanted in goats with an approximate 15% reduction in retention force by drilling longitudinally orientated grooves on the side of the stem. In this current study, we aimed to histologically evaluate the bony apposition towards this stem and correlate this apposition with the pullout force. METHODS: We analyzed the femora of 22 goats after stem removal. All stems remained in place for 6 months, and the goats were allowed regular loading of the hip during this time. For histological evaluation, all femora were immersed in EDTA and decalcified until sufficiently soft for standard technique preparation. We evaluated bone apposition, the presence of foreign particle debris and other factors. The apposition was evaluated with a scoring system based on semi-quantitative bone apposition in four quadrants. Kappa statistics were calculated for the score. We correlated the retention force with the amount of bone apposition. RESULTS: The stem drilling was the only significant factor influencing the retention force (p = 0.020). The bone apposition Kappa score comparing poor and good apposition scores was fair (κ = 0.4, 95% CI 0.00-0.88). Signs of foreign body reaction were noted in 5 of 22 goats. CONCLUSIONS: Based on the current findings in an experimental goat model, it appears that the effect of drilling tissue/bone out of the longitudinal grooves has a more significant impact on the retention force required to remove the stem than the amount of bone apposition outside the stem grooves. This observation may be further explored in the research of stem designs that are potentially easier to remove.
Assuntos
Artroplastia de Quadril/instrumentação , Fêmur/cirurgia , Articulação do Quadril/cirurgia , Prótese de Quadril , Animais , Artroplastia de Quadril/efeitos adversos , Fenômenos Biomecânicos , Fêmur/fisiopatologia , Cabras , Articulação do Quadril/fisiopatologia , Modelos Animais , Desenho de Prótese , Falha de Prótese , Estresse Mecânico , Fatores de Tempo , Suporte de CargaRESUMO
BACKGROUND: The quality of the data in the Cause of Death Registry is crucial to produce reliable statistics on causes of death. The Cancer Registry of Norway uses data from the Norwegian Patient Register to request information from hospitals regarding patients registered with cancer in the patient registry, but not in the cancer registry. We wanted to investigate whether data from the Norwegian Patient Register can also be used to advantage in the Cause of Death Registry. MATERIAL AND METHOD: Data from the Cause of Death Registry on deaths that occurred during the period 2009 2011 (N = 124,098) were collated with data on contact with somatic hospitals and psychiatric institutions during the last year of life, retrieved from the Norwegian Patient Register. Causes of death were grouped in the same way as in standard statistics on causes of death. RESULTS: Out of 124,098 deaths, altogether 34.9% occurred in somatic hospitals. A total of 80.9% of all deceased had been admitted to a somatic hospital and/or had attended an outpatient consultation during their last year of life. The proportion with hospital contact was highest for those whose cause of death was cancer. In cases of unknown/unspecified cause of death, more than half also had contact with hospitals, but the majority of these were registered with only outpatient consultations. Altogether 5.4% of all deceased had been admitted to and/or had an outpatient consultation in a psychiatric institution during their last year of life. For those whose cause of death was suicide, this proportion amounted to 41.8%. INTERPRETATION: In case of incomplete information on the cause of death, data from the Norwegian Patient Register can supply valuable information on where the patient has been treated, thus enabling the Cause of Death Registry to contact the hospitals in question. However, any potential benefit is restricted by the fact that deceased persons with unknown/unspecified causes of death had less frequently been admitted to hospital during their last year of life.
Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Causas de Morte , Hospitalização/estatística & dados numéricos , Hospitais Psiquiátricos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/mortalidade , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Noruega/epidemiologia , Garantia da Qualidade dos Cuidados de Saúde , Sistema de Registros , Suicídio/estatística & dados numéricosRESUMO
One hundred years ago, forensic examination of deceased infants was not an uncommon task for doctors in Norway. The key questions were whether the infant had been born alive and whether the manner of death could be explained. The decomposition of the corpses, which had often lain hidden long before they were examined, posed a considerable problem. Notwithstanding the known shortcomings in the criteria used for assessment of breathing (the lung flotation test), and the fact that the bodies were often severely decomposed, the lung flotation test and the supposed signs of asphyxiation were used indiscriminately. This absence of association between theoretical knowledge and practice may have had its origin in societal conditions in which clandestine birth and the killing of newborns was not uncommon.
Assuntos
Patologia Legal/história , Mortalidade Infantil/história , Pulmão/patologia , Causas de Morte , Feminino , História do Século XX , Humanos , Recém-Nascido , Infanticídio/história , Nascido Vivo , Noruega , Gravidez , NatimortoRESUMO
BACKGROUND: Geographical differences in health outcomes are reported in many countries. Norway has led an active policy aiming for regional balance since the 1970s. Using data from the Global Burden of Disease Study (GBD) 2019, we examined regional differences in development and current state of health across Norwegian counties. METHODS: Data for life expectancy, healthy life expectancy (HALE), years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) in Norway and its 11 counties from 1990 to 2019 were extracted from GBD 2019. County-specific contributors to changes in life expectancy were compared. Inequality in disease burden was examined by use of the Gini coefficient. FINDINGS: Life expectancy and HALE improved in all Norwegian counties from 1990 to 2019. Improvements in life expectancy and HALE were greatest in the two counties with the lowest values in 1990: Oslo, in which life expectancy and HALE increased from 71·9 years (95% uncertainty interval 71·4-72·4) and 63·0 years (60·5-65·4) in 1990 to 81·3 years (80·0-82·7) and 70·6 years (67·4-73·6) in 2019, respectively; and Troms og Finnmark, in which life expectancy and HALE increased from 71·9 years (71·5-72·4) and 63·5 years (60·9-65·6) in 1990 to 80·3 years (79·4-81·2) and 70·0 years (66·8-72·2) in 2019, respectively. Increased life expectancy was mainly due to reductions in cardiovascular disease, neoplasms, and respiratory infections. No significant differences between the national YLD or DALY rates and the corresponding age-standardised rates were reported in any of the counties in 2019; however, Troms og Finnmark had a higher age-standardised YLL rate than the national rate (8394 per 100â000 [95% UI 7801-8944] vs 7536 per 100â000 [7391-7691]). Low inequality between counties was shown for life expectancy, HALE, all level-1 causes of DALYs, and exposure to level-1 risk factors. INTERPRETATION: Over the past 30 years, Norway has reduced inequality in disease burden between counties. However, inequalities still exist at a within-county level and along other sociodemographic gradients. Because of insufficient Norwegian primary data, there remains substantial uncertainty associated with regional estimates for non-fatal disease burden and exposure to risk factors. FUNDING: Bill & Melinda Gates Foundation, Research Council of Norway, and Norwegian Institute of Public Health.
Assuntos
Carga Global da Doença , Expectativa de Vida , Efeitos Psicossociais da Doença , Expectativa de Vida Saudável , Humanos , Noruega/epidemiologiaRESUMO
BACKGROUND: At the turn of 2007/2008, four Norwegian men died after ingestion of commercially available supposedly denatured ethanol. MATERIAL AND METHODS: The four deaths are presented and discussed. RESULTS: Methanol concentrations, consistent with lethal methanol poisoning, were detected in blood and urine for all four. The imbibed mixture was subsequently shown to contain a 70/30 mixture of methanol/ethanol. INTERPRETATION: The events emphasize the importance of investigating methanol findings from deceased to identify the source, and that investigations are instigated promptly to prevent further exposure.
Assuntos
Metanol/intoxicação , Solventes/intoxicação , Evolução Fatal , Toxicologia Forense , Humanos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologiaRESUMO
OBJECTIVE: This study aimed to determine the level of misattribution of prostate cancer deaths in Norway based on the county of Vestfold in the years 2009-2014. MATERIALS AND METHODS: The study included 328 patients registered as dead from prostate cancer (PCD; part I of death certificate), 126 patients with prostate cancer as other significant condition at death (OCD; part II of death certificate) and 310 patients who died with a diagnosis of prostate cancer not registered on the death certificate (PC-DCneg) in Vestfold County in 2009-2014. The complete cohort with patients' names and dates of birth was provided by the Norwegian Institute of Public Health and the Norwegian Cancer Registry. The true cause of death of all patients was evaluated based on patient journals. RESULTS: Over-reporting of prostate cancer deaths in the PCD group was 33% while under-reporting in the OCD and PC-DCneg groups was 19% and 5%, respectively. The correlation between registered and observed causes of death was 0.81 (95% confidence interval 0.78-0.83). Misattribution of prostate cancer deaths increased significantly with patient age and decreasing Gleason score. CONCLUSIONS: Prostate cancer mortality statistics in Norway are relatively accurate for patients aged <75 years at death. However, overall accuracy of cause of death assignment is significantly reduced by misattribution among older patients (> 75 years), who represent the large majority of prostate cancer deaths. Over-reporting of prostate cancer deaths among elderly people may not be an exclusively Norwegian phenomenon and may affect prostate cancer mortality statistics in other countries.
Assuntos
Causas de Morte , Atestado de Óbito , Neoplasias da Próstata/mortalidade , Estatística como Assunto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Noruega/epidemiologia , Neoplasias da Próstata/patologia , Sistema de RegistrosRESUMO
Amniotic fluid embolism (AFE) is a rare, but potentially fatal complication of pregnancy, with an incidence between 1 in 8000 and 1 in 80,000 pregnancies. The pathogenesis is not fully understood, but the generally accepted belief is that amniotic fluid enters the mother's circulation, most commonly via tears in the lower uterine segment. In the fluid there are substances with pro-inflammatory, vasospastic and pro-coagulative properties. AFE after blunt trauma is very rare, only described a few times in the literature. We report a case of fatal AFE after probable minor blunt trauma to the abdomen and give a review of the literature.
Assuntos
Traumatismos Abdominais/complicações , Embolia Amniótica/etiologia , Parada Cardíaca/etiologia , Ferimentos não Penetrantes/complicações , Traumatismos Abdominais/terapia , Adulto , Embolia Amniótica/terapia , Evolução Fatal , Feminino , Parada Cardíaca/terapia , Humanos , Gravidez , Ressuscitação , Ferimentos não Penetrantes/terapiaRESUMO
Mechanical chest compression may be necessary to make coronary intervention possible during resuscitation. We report our experience using the Lund University Cardiac Arrest System (LUCAS, Jolife, Lund, Sweden) which is a gas-driven sternal compression device that incorporates a suction cup for active decompression. During the last 13 months LUCAS has been used in our catheterisation laboratory to maintain adequate organ perfusion pressure in 13 patients with cardiac arrest or severe hypotension and bradycardia (male/female ratio 1.6, mean age 59+/-19). The mean compression time was 105+/-60min (range 45-240), and the mean systolic and diastolic blood pressure obtained was 81+/-23 and 34+/-21mmHg, respectively. Angiography and eventually percutanous coronary intervention was possible in all cases during ongoing automatic chest compression. Three patients survived the procedure, but no patients were discharged alive. In two cases we found inadequate flow in the anterior descending artery, and in one case the invasive measurements revealed inadequate coronary perfusion pressure. There were no excessive intra-thoracic or intra-abdominal injuries. We conclude that the LUCAS device is suitable during cardiac catheterisation and intervention, and the device ensures an adequate systemic blood pressure in most patients without life-threatening injuries.
Assuntos
Circulação Assistida/instrumentação , Cateterismo Cardíaco , Reanimação Cardiopulmonar/métodos , Parada Cardíaca/terapia , Massagem Cardíaca/instrumentação , Adulto , Idoso , Circulação Assistida/estatística & dados numéricos , Reanimação Cardiopulmonar/efeitos adversos , Desenho de Equipamento , Feminino , Parada Cardíaca/diagnóstico , Massagem Cardíaca/efeitos adversos , Massagem Cardíaca/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Sudden cardiac death in a young person is rare. In contrast to older persons, where atherosclerotic heart disease is the most common cause; cardiomyopathies, myocarditis, commotio cordis and coronary artery anomalies are more common in the young. MATERIAL AND METHODS: This report comprises the autopsy findings in two young persons who died suddenly and a short review of relevant literature. RESULTS: Coronary artery anomalies were demonstrated in both cases. The left coronary artery emerged from the right sinus of Valsalva and passed between the aorta and the pulmonary artery. In one of the cases there was a recent myocardial infarction. INTERPRETATION: The most frequent coronary anomalies are of no clinical significance, but some are associated with an increased risk of sudden death. One of the most important anomalies is where the left coronary artery arises from the right sinus of Valsalva and passes between the aorta and the pulmonary artery.
Assuntos
Anomalias dos Vasos Coronários/complicações , Morte Súbita Cardíaca/etiologia , Morte Súbita/etiologia , Adolescente , Adulto , Autopsia , Anomalias dos Vasos Coronários/patologia , Morte Súbita/patologia , Feminino , Patologia Legal , Humanos , Masculino , Infarto do Miocárdio/patologia , Fatores de RiscoRESUMO
Multiple intestinal atresia (MIA) is a rare cause of bowel obstruction that is sometimes associated with a combined immunodeficiency (CID), leading to increased susceptibility to infections. The factors underlying this rare disease are poorly understood. We characterized the immunological and intestinal features of 6 unrelated MIA-CID patients. All patients displayed a profound, generalized lymphocytopenia, with few lymphocytes present in the lymph nodes. The thymus was hypoplastic and exhibited an abnormal distribution of epithelial cells. Patients also had profound disruption of the epithelial barrier along the entire gastrointestinal tract. Using linkage analysis and whole-exome sequencing, we identified 10 mutations in tetratricopeptide repeat domain7A (TTC7A), all of which potentially abrogate TTC7A expression. Intestinal organoid cultures from patient biopsies displayed an inversion of apicobasal polarity of the epithelial cells that was normalized by pharmacological inhibition of Rho kinase. Our data indicate that TTC7A deficiency results in increased Rho kinase activity, which disrupts polarity, growth, and differentiation of intestinal epithelial cells, and which impairs immune cell homeostasis, thereby promoting MIA-CID development.