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Purpose: We aimed to analyze the risk of hereditary hemochromatosis (HH) among first-generation and second-generation immigrants in Sweden using Swedish-born individuals and Swedish-born individuals with Swedish-born parents as referents, respectively. Methods: All individuals aged 18 years of age and older, n = 6,180,500 in the first-generation study, and n = 4,589,930 in the second-generation study were included in the analyses. HH was defined as at least one registered diagnosis International Classification of Diseases 10th edition (E83.1) in the National Patient Register between January 1, 1998 and December 31, 2018. Cox regression was used to estimate the hazard ratios (HRs) with 99% confidence intervals (CI) owing to multiple testing, of incident HH with adjustments for age, cancer, other comorbidities, and socio-demographics. Results: In the first-generation study, there were 5,112 cases of HH, and in the second-generation study 4,626 cases of HH. The adjusted HRs for first-generation men and women overall were 0.72 (99% CI: 0.63-0.82) and 0.61 (99% CI: 0.52-0.72), respectively, and for the second-generation men and women 0.72 (99% CI: 0.62-0.83) and 0.97 (99% CI: 0.83-1.14), respectively, with a higher risk found only among first-generation men from Western Europe, HR 1.47 (99% CI: 1.05-2.06), compared to the control group. Conclusions: Our findings indicate that the overall risk of HH was lower among both first-generation and second-generation immigrants when compared to individuals born in Sweden or with Swedish-born parents. An elevated risk for HH was observed exclusively among first-generation men originating from Western Europe. These findings represent new knowledge and should be of global interest.
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Emigrantes e Imigrantes , Hemocromatose , Humanos , Suécia/epidemiologia , Hemocromatose/genética , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos de Coortes , Idoso , Fatores de Risco , Modelos de Riscos Proporcionais , Adulto Jovem , Adolescente , Sistema de Registros , IncidênciaRESUMO
INTRODUCTION: Accumulating evidence suggests the significant involvement of GADD45G in the development of various cancers. This study investigates GADD45G's involvement and methylation status in endometrial cancer (EC), along with molecular mechanisms and potential therapies. METHODS: The expression of GADD45G in EC tissues and controls was evaluated using RNA-seq, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting (WB). Methylation-specific PCR (MSP) evaluated GADD45G's methylation status. Protein-protein interaction (PPI) prediction identified potential interactors of GADD45G, and co-immunoprecipitation (co-IP) confirmed GADD45G interact with Cyclin-dependent kinase 1 (CDK1) and cyclin B1 (CCNB1). Several cell behavior assays were conducted in both in vitro and in vivo settings to comprehensively understand the impact of GADD45G dysregulation in EC. RESULTS: Our findings revealed a significant decrease in the expression of GADD45G in endometrial cancer tissues and cells, which was attributed to its methylation status. Reduced GADD45G expression correlated with increased invasive behaviors in EC cells. Furthermore, GADD45G negatively regulated CDK1 and CCNB1, promoting invasive behaviors at transcript and protein levels. CONCLUSION: This study demonstrated that the downregulation of GADD45G, mediated by methylation, facilitates the invasive behaviors of EC cells through interaction with the CDK1/CCNB1. These findings enhance understanding of the molecular mechanisms underlying endometrial cancer and suggest potential therapeutic strategies targeting GADD45G for treatment.
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Proteína Quinase CDC2 , Ciclina B1 , Metilação de DNA , Neoplasias do Endométrio , Proteínas GADD45 , Regulação Neoplásica da Expressão Gênica , Animais , Feminino , Humanos , Camundongos , Proteína Quinase CDC2/metabolismo , Proteína Quinase CDC2/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Ciclina B1/genética , Ciclina B1/metabolismo , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/metabolismo , Proteínas GADD45/genética , Proteínas GADD45/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
AIMS: To examine whether vulvovaginal candidiasis (VVC) precedes type 2 diabetes and to quantify the possible time period between VVC and subsequent diabetes. MATERIAL AND METHODS: We conducted a nationwide retrospective primary healthcare study including 1 838 929 women aged 35-65 years in Sweden (2007-2018). Cox regression models were used to examine associations between VVC and type 2 diabetes, while controlling for possible confounders. Propensity-score-weighted analysis was also conducted. RESULTS: The incidence rate of diabetes per 1000 person-years was 3.06 (95% confidence interval [CI] 3.05-3.08) in women without preceding VVC and 4.05 (95% CI 3.86-4.24) in women with preceding VVC. The incidence rate was particularly high in women aged 55 years and older with VVC: 9.56 (95% CI 8.01-11.11). Women with VVC had a hazard ratio (HR) of 1.41 (95% CI 1.28-1.55) for diabetes compared to women without VVC in the multivariable-adjusted model. The corresponding HR was 1.63 (95% CI 1.53-1.74) in propensity-score-weighted analysis. Women with prior VVC also seemed to have a stronger risk of diabetes with older age, particularly after the age of 55 years. The mean (range) time between VVC and subsequent diabetes was 0.57 (0-2) years, depending on the age of the woman. CONCLUSION: We found temporal associations between VVC and diabetes. The findings demonstrate that the presence of VVC may indicate a future diagnosis of diabetes, especially in women aged 55 years and older. This knowledge could be valuable for clinicians when treating women with VVC.
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Candidíase Vulvovaginal , Diabetes Mellitus Tipo 2 , Humanos , Feminino , Pessoa de Meia-Idade , Candidíase Vulvovaginal/epidemiologia , Candidíase Vulvovaginal/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Estudos Retrospectivos , Adulto , Suécia/epidemiologia , Idoso , Incidência , Fatores de Risco , Estudos de CoortesRESUMO
The effects of cast iron pipe corrosion on water quality risk and microbial ecology in drinking water distribution systems (DWDSs) were investigated. It was found that trihalomethane (THMs) concentration and antibiotic resistance genes (ARGs) increased sharply in the old DWDSs. Under the same residual chlorine concentration conditions, the adenosine triphosphate concentration in the effluent of old DWDSs (Eff-old) was significantly higher than that in the effluent of new DWDSs. Moreover, stronger bioflocculation ability and weaker hydrophobicity coexisted in the extracellular polymeric substances of Eff-old, meanwhile, iron particles could be well inserted into the structure of the biofilms to enhance the mechanical strength and stability of the biofilms, hence enhancing the formation of THMs. Old DWDSs significantly influenced the microbial community of bulk water and triggered stronger microbial antioxidant systems response, resulting in higher ARGs abundance. Corroded cast iron pipes induced a unique interaction system of biofilms, chlorine, and corrosion products. Therefore, as the age of cast iron pipes increases, the fluctuation of water quality and microbial ecology should be paid more attention to maintain the safety of tap water.
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Biofilmes , Ferro , Qualidade da Água , Abastecimento de Água , Corrosão , Microbiologia da Água , Água Potável/microbiologia , Água Potável/química , Resistência Microbiana a Medicamentos/genética , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Trialometanos/análiseRESUMO
The human sex ratio at birth (SRB) undergoes temporary changes around a mean proportion of 0.51 male births. SRB has been well studied for historical, geographical, and secular trends, but until now not linked to health outcomes in the total population, e.g. for cardiovascular disease (CVD) or mortality during follow-up of birth cohorts. We used linkage analysis based on national registers in Sweden that cover all births from 1900 to 2016. SRB at birth was calculated by every 10-year birth cohort in all survivors living in 1997 for a follow-up analysis of risk of CVD and mortality with data from national registers. When the highest quartile of SRB was used as reference, a slightly increased risk of fatal CVD (HR 1.03 (95% confidence intervals, CI): 1.02-1.04), non-fatal CVD (HR 1.01; 95%CI: 1.01-1.02) and mortality (HR 1.02; 95%CI, 1.01-1.03) was found after full adjustments in men belonging to the lowest SRB quartile. A similar pattern was also found for fatal CHD in women. in the lowest SBR quartile compared to the highest, HR 1.03 (95%CI: 1.02-1.05). In conclusion, in birth cohorts with a relatively lower than expected number of males born, long-term adverse health effects were observed with slightly increased cardiovascular risk and total mortality at the population level. This could indicate that men belonging to so-called "culled cohorts" in a developed country during the 20th century are characterized by a slightly increased risk that could reflect negative early life influences and environmental exposures in pregnant women resulting in selective loss of male embryos or fetuses. In a public health perspective SRB could be of some importance to monitor as an aspect of birth statistics linked to relatively minor population health effects.
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PURPOSE: We aimed at analysing the risk of congestive heart failure (CHF) among first- and second-generation immigrants in younger age groups. METHODS: All individuals aged 18-54 years, n = 3 973 454 in the first-generation study and n = 3 817 560 in the second-generation study, were included. CHF was defined as at least one registered diagnosis in the National Patient Register between 1 January 1998 and 31 December 2018. Cox regression analysis was used to estimate the relative risk [hazard ratios (HRs) with 99% confidence intervals (CIs)] of incident CHF with adjustments for age, co-morbidities and socio-demographics. RESULTS: In the first-generation study, a total of 85 719 cases of CHF were registered, 54 369 men and 31 350 women, where fully adjusted models showed HRs for all foreign-born men of 1.12 (99% CI 1.06-1.17) and for women of 0.99 (0.92-1.05). Groups with higher risk included men from Eastern Europe, Central Europe, Africa and Asia and women from Africa and Asia, and a lower risk was found among Latin American women. In the second-generation study, a total of 88 999 cases of CHF were registered, 58 403 men and 30 596 women, where fully adjusted models showed HRs for second-generation men of 1.04 (0.99-1.09) and women of 0.97 (0.90-1.04). CONCLUSIONS: The higher risk in some foreign-born groups needs to be paid attention to in clinical practice. The fact that almost all increased risks were attenuated and absent in second-generation immigrants suggests that lifestyle and environmental factors are more important than genetic differences in the risk of CHF.
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BACKGROUND: The impact of bacterial vaginosis on women's health is an increasing concern; however, the effect of the obesity index on bacterial vaginosis is controversial. We investigated the association between body mass index and bacterial vaginosis in women in the United States. METHODS: This was a cross-sectional study which obtained the data from the National Health and Nutrition Examination Survey from 2001 to 2004, in which weighted multivariate regression and logistic regression analyses were performed to explore the independent relationship between body mass index and bacterial vaginosis. Subgroup analyses and smoothed curve fitting were also performed. RESULTS: A total of 5,428 participants were enrolled, and the findings show that the participants with higher body mass index tended to have a higher incidence of bacterial vaginosis. In the fully adjusted model, a positive association between bacterial vaginosis and body mass index was observed (Odd's ratio = 1.03, 95% Confidence interval, 1.01-1.04). The subgroup analysis showed that this positive association was significant in non-Hispanic White individuals (Odd's ratio = 1.0327, 95% Confidence interval, 1.0163, 1.0493). CONCLUSION: Increased bacterial vaginosis positivity may be associated with an increased body mass index.
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Índice de Massa Corporal , Inquéritos Nutricionais , Vaginose Bacteriana , Humanos , Vaginose Bacteriana/epidemiologia , Vaginose Bacteriana/microbiologia , Feminino , Adulto , Estudos Transversais , Estados Unidos/epidemiologia , Prevalência , Pessoa de Meia-Idade , Adulto Jovem , Obesidade/epidemiologia , Obesidade/complicaçõesRESUMO
BACKGROUND: There is a lack of studies on sarcoidosis among immigrants, which is of interest as there may be genetic and environmental characteristics affecting immigrants from certain countries. We aimed to study hazard ratios (HRs) of sarcoidosis in first- and second-generation immigrants, comparing them with native Swedes in the total adult Swedish population. METHODS: We conducted a nationwide study of individuals ≥18 y of age. Sarcoidosis was defined as at least two registered diagnoses in the National Patient Register between 1 January 1998 and 31 December 2018. Cox regression analysis was used to estimate HRs with 99% confidence intervals (CIs) of first registration of sarcoidosis in first- and second-generation immigrants compared with native Swedes. The Cox regression models were stratified by sex and adjusted for age, comorbidities and sociodemographic characteristics. RESULTS: In total, 6 175 251 were included in the first-generation study, with 12 617 cases of sarcoidosis, and 4 585 529 in the second-generation study, with 12 126 cases. The overall sarcoidosis risk was lower in foreign-born men (fully adjusted HR 0.63 [99% CI 0.57 to 0.69]) but not in foreign-born women (fully adjusted HR 0.98 [99% CI 0.90 to 1.06]). The overall risk was slightly lower in second-generation immigrants (HR 0.82 [99% CI 0.78 to 0.88]). Women from Asia exhibited a higher risk (HR 1.25 [99% CI 1.02 to 1.53)], while a potential trend was observed among women from Africa (HR 1.47 [99% CI 0.99 to 2.19]). CONCLUSIONS: Sarcoidosis risk was lower in foreign-born men but not in women and also lower in second-generation immigrants.
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BACKGROUND: Little is known about risks of hypertensive disorders of pregnancy in both first- and second-generation immigrant women in Europe and other Western countries; such knowledge may help elucidate the influence of genetic versus social factors on such risks. We aimed to study both first- and second-generation immigrant women for the presence of all types of hypertension (preexisting hypertension, gestational hypertension, preeclampsia, and eclampsia) during pregnancy. METHODS AND RESULTS: A cohort study was conducted using data derived from the Swedish National Birth Register, the National Patient Register, and the Total Population Register. We used Cox regression analysis to compute hazard ratios (HRs) and 99% CIs while adjusting for sociodemographic factors and comorbidities. The first-generation study included a total of 1 084 212 deliveries and 68 311 hypertension cases, and the second-generation study included 989 986 deliveries and 67 505 hypertension cases. The fully adjusted HR (with 99% CI) for hypertension in pregnancy among first-generation immigrant women was 0.69 (0.66-0.72), and among second-generation immigrant women, it was 0.88 (0.86-0.91), compared with Swedish-born women with 2 Swedish-born parents. Women born in Finland or with parent(s) from Finland had higher risks, with fully adjusted HRs (99% CIs) of 1.30 (1.18-1.43) and 1.12 (1.07-1.17), respectively. CONCLUSIONS: Both first- and second-generation immigrant women had overall lower risks of hypertension in pregnancy compared with other Swedish women. However, the risk reduction was less pronounced in second-generation compared with first-generation immigrant women, suggesting that environmental factors in Sweden may have an important influence on risk of hypertension during pregnancy.
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Emigrantes e Imigrantes , Hipertensão Induzida pela Gravidez , Humanos , Feminino , Gravidez , Estudos de Coortes , Gestantes , Suécia/epidemiologia , Hipertensão Induzida pela Gravidez/epidemiologia , Parto , Fatores de RiscoRESUMO
Patients with bipolar disorder have higher rates of type 2 diabetes (T2D) compared to the general population. Neighbourhood deprivation is associated with T2D and bipolar disorder. The aim of this study was to explore the potential effect of neighbourhood deprivation on incident T2D in patients with bipolar disorder. This nationwide open cohort study (1997-2018) included adults in Sweden ≥20 years with bipolar disorder (90,780 patients) to examine the subsequent risk of T2D. The association between neighbourhood deprivation and T2D was explored using Cox regression analysis, with hazard ratios (HRs) and 95% confidence intervals (95% CIs). All models were conducted in both men and women and adjusted for individual-level sociodemographic factors and comorbidities. Neighbourhood deprivation was significantly associated with T2D in patients with bipolar disorder. The HRs were 1.61 (95% CI 1.40-1.86) for men and 1.83 (1.60-2.10) for women living in high deprivation neighbourhoods compared to those from low deprivation neighbourhoods. After adjustment, these results remained significant: 1.35 (1.17-1.56) in men and 1.39 (1.20-1.60) in women living in high deprivation neighbourhoods. The suggested graded association of higher incident T2D among patients with bipolar disorder, observed when levels of neighbourhood deprivation increased, raises important clinical and public health concerns. The results may help develop a contextual approach to prevention of T2D in patients with bipolar disorder that includes the neighbourhood environment.
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Transtorno Bipolar , Diabetes Mellitus Tipo 2 , Adulto , Masculino , Humanos , Feminino , Seguimentos , Diabetes Mellitus Tipo 2/epidemiologia , Estudos de Coortes , Transtorno Bipolar/epidemiologia , Suécia/epidemiologia , Características de Residência , Fatores SocioeconômicosRESUMO
Studying the mechanisms of the spin Hall effect (SHE) is essential for the fundamental understanding of spintronic physics. By now, despite the intensive studies of SHE on heavy metal (HM)/metallic magnet heterostructures, the SHE on HM/ferrimagnetic insulator (FMI) heterostructures still remains elusive. Here, we study the mechanism of SHE in the Pt/Tm3Fe5O12 (TmIG) heterostructure. We first tune the crystallinity and resistivity of Pt by an annealing method, and then study the spin-orbit torque (SOT) in the tuned-Pt/TmIG devices. The SOT generation efficiency per unit electric field and spin Hall angle were obtained, which are insensitive to the annealing temperature. We further demonstrate that the intrinsic contribution in the moderately dirty regime is responsible for the SHE in our Pt/TmIG bilayer. Our study provides an important piece of information for the SHE in FMI-based spintronic physics.
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BACKGROUND: Associations between different cancer types are known. The affirmation of the risk for non-ovarian cancer after ovarian borderline tumors (BOT) is, however, sparse. AIM: To analyze the risk of subsequent or simultaneous cancers in women with BOTs compared with the general female Swedish population. METHODS: An open cohort study (1995-2018) was conducted where a diagnosis of BOTs as well as subsequent or simultaneous cancer diagnoses were obtained from the Swedish Cancer Register and matched to the Total Population Register. Each woman with BOT was followed until non-ovarian cancer, death or emigration and could only be included once for the outcome. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) for specific non-ovarian cancers were analyzed. RESULTS: The 4998 women with serous and mucinous BOTs were diagnosed during 1995-2018 with a mean age of 55.7 years (SD 16.0) at diagnosis. Compared with the general female population, women with BOTs had increased risks for non-ovarian cancer in colon (SIR = 2.5; 95% CI 2.0-3.1), rectum (SIR = 1.7; 95% CI 1.1-2.5), small intestine (SIR = 5.0; 95% CI 2.3-9.5), cervix (SIR = 2.5; 95% CI 1.4-4.2), endometrium (SIR = 2.4; 95% CI 1.9-3.1), pancreas (SIR = 2.3; 95% CI 1.4-3.5), upper aerodigestive tract (SIR = 2.2; 95% CI 1.2-3.8), lung (SIR = 1.8; 95% CI 1.4-2.3), kidney (SIR = 2.3; 95% CI 1.4-3.7) and bladder (SIR = 1.8; 95% CI 1.1-2.8). Among women with serous BOTs, the risk of thyroid gland cancer (SIR = 3.1; 95% CI 1.2-6.4) was also increased. Lung and pancreas cancer showed increased risks more than 1 year after a diagnosis of BOT. CONCLUSIONS: This Swedish population-based study demonstrated an increased risk of multiple malignancies including lung and pancreatic cancers beyond the first year of diagnosis in patients with borderline ovarian tumors (BOTs), suggesting a potential shared etiology.
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Neoplasias Ovarianas , Humanos , Feminino , Pessoa de Meia-Idade , Estudos de Coortes , Suécia/epidemiologia , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Fatores de Risco , IncidênciaRESUMO
Poorly cohesive duodenal carcinoma mixed with signet ring cell carcinoma is very rare, and no cases have been reported. When distant metastasis occurs, it is very easy to be misdiagnosed. We report the first case of a 52-year-old man with poorly cohesive carcinoma of the duodenum mixed with signet ring cell carcinoma with systemic metastasis. The process of its diagnosis and differential diagnosis is highlighted.
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BACKGROUND AND AIMS: Gestational diabetes is more common in many first-generation immigrant women in Europe and other Western countries. Less is known about second-generation immigrant women; such knowledge is needed to understand generational influences on diabetes risk. We aimed to study second-generation immigrant women regarding the presence of all types of diabetes during pregnancy. METHODS AND RESULTS: A cohort study was conducted using the Swedish National Birth Register, the National Patient Register, and the Total Population Register. We used Cox regression analysis to compute hazard ratios (HRs) and 99% confidence intervals (99% CI) for any diabetes during pregnancy and specific subtypes (gestational diabetes, pre-existing diabetes type 1, pre-existing diabetes type 2) in second-generation immigrant women compared with Swedish-born women with two Swedish-born parents while adjusting for sociodemographic factors, family history of diabetes, body mass index, smoking habits, and comorbidities. The study population included a total of 989,986 deliveries and 17,938 diabetes cases. The fully adjusted HR (with 99% CI) for any type of diabetes during pregnancy among second-generation immigrant women was 1.11 (1.05-1.18). Higher risks were found in women with parents from Africa, Asia, or Eastern Europe, as well as Denmark. A lower risk for pre-existing type 1 diabetes was found overall and for women with parents from most geographic regions. CONCLUSION: In this national cohort study, the risk of all types of diabetes during pregnancy was increased in second-generation immigrant women. Diabetes prevention and treatment is especially important in these women both before and during pregnancy.
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Diabetes Mellitus Tipo 1 , Diabetes Gestacional , Emigrantes e Imigrantes , Gravidez , Humanos , Feminino , Estudos de Coortes , Suécia/epidemiologia , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Europa (Continente)/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Neighborhood deprivation has been found associated with both type 2 diabetes and lung cancer. The aim of this study was to examine the potential association between neighborhood deprivation and lung cancer incidence or mortality in individuals diagnosed with type 2 diabetes. The results may identify a new risk or prognostic factor for lung cancer in this important subgroup and help develop a more contextual approach to prevention that includes neighborhood environment. METHODS AND FINDINGS: The study population included adults (n = 613,650) aged ≥ 30 years with type 2 diabetes during 2005 to 2018 in Sweden. Cox regression was used to compute hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incidence or mortality of lung cancer associated with neighborhood deprivation. All models were conducted in both men and women and adjusted for individual-level characteristics (e.g. age, smoking- and alcohol-related comorbidities, sociodemographic factors). The cumulative incidence and mortality for lung cancer were 1.08% (95% CI, 1.06 to 1.11) and 0.93% (0.90 to 0.95), respectively, in the study population during the study period. Neighborhood deprivation was associated with both incidence and mortality of lung cancer in patients with type 2 diabetes independently of the individual-level characteristics. In the fully adjusted models, comparing high- with low-deprivation neighborhoods, the HRs for lung cancer incidence were 1.21 (1.10 to 1.33) in men and 1.08 (0.95 to 1.21) in women. The corresponding HRs for lung cancer mortality were 1.04 (1.00 to 1.07) in men and 0.97 (0.94 to 1.00) in women. Competing risk analyses including cardiovascular mortality attenuated the results. CONCLUSION: In this large cohort of individuals with type 2 diabetes, we found higher lung cancer incidence and mortality in patients living in areas with high neighborhood deprivation, even after adjusting for individual-level characteristics. These findings may help develop a more contextual approach that includes the neighborhood environment when allocating resources for disease prevention and care in patients with type 2 diabetes. These findings could also help inform clinical care for patients with type 2 diabetes, particularly those living in deprived neighborhoods.
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Diabetes Mellitus Tipo 2 , Neoplasias Pulmonares , Adulto , Masculino , Humanos , Feminino , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Neoplasias Pulmonares/epidemiologia , Comorbidade , Fumar , Características de Residência , Fatores SocioeconômicosRESUMO
INTRODUCTION: Pelvic girdle pain during and after pregnancy is a major public health problem with significant daily problems for affected women and their families. There is now accumulating evidence that pregnancy-related pelvic girdle pain originates from the sacroiliac joints and the pubic symphysis as well as their extra-articular ligaments. However, the heritability of the disease remains to be determined. We hypothesized that there is an increased familial risk of pregnancy-related pelvic girdle pain. MATERIAL AND METHODS: A population-based national database linkage registry study of approximately 9.3 million individuals within 4.2 million families in Sweden with a recruitment period from 1997 to 2018. The Swedish Multi-generation register was used to find female pairs of twins, full siblings, half-siblings and first cousins where both in the pairs had a completed pregnancy. The outcome measure was diagnosis of pregnancy-related pelvic girdle pain (International Classification of Diseases-10 O26.7 [1997-2018]) in the first pregnancy. Data was obtained from the Swedish Hospital Discharge Register, the Swedish Outpatient Care Register, the Swedish Medical Birth Register, the Primary Healthcare Register, and Medical Treatment Register. Cox regression analysis was used to calculate adjusted estimated effect of the exposure variable familial history of pregnancy-related pelvic girdle pain on the outcome variable pregnancy-related pelvic girdle pain at first birth. RESULTS: From the registers, 1 010 064 women pregnant with their first child within 795 654 families were collected. In total, 109 147 women were diagnosed with pregnancy-related pelvic girdle pain. The adjusted hazard ratio for a familial risk of pregnancy-related pelvic girdle pain was 2.09 (95% CI 1.85-2.37) among twins (monozygotic and dizygotic), 1.78 (95% CI 1.74-1.82) in full siblings, 1.16 (95% CI 1.06-1.28) in half-siblings from the mother, 1.09 (95% CI 1.024-1.16) in half-siblings from the father and 1.09 (95% CI 1.07-1.12) in first cousins. CONCLUSIONS: This nationwide observational study showed a familial clustering of pregnancy-related pelvic girdle pain. The hazard ratio for the condition was associated with the degree of relatedness, suggesting that heredity factors contribute to the development of pregnancy-related pelvic girdle pain. There is no causal treatment available for pregnancy-related pelvic girdle pain and further studies are now encouraged to clarify the specific genetic factors that contribute to the disease and for future targeted interventions.
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Hereditariedade , Dor da Cintura Pélvica , Complicações na Gravidez , Feminino , Humanos , Gravidez , Família , Predisposição Genética para Doença , Dor da Cintura Pélvica/epidemiologia , Dor da Cintura Pélvica/genética , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/genética , Suécia/epidemiologiaRESUMO
Sepsis is a severe condition, representing a significant public health concern, especially in the elderly. There is, however, little insight into the potential effects of sociodemographic factors and comorbidities on sepsis incidence and how these factors interact. This was a nationwide open cohort study including individuals (N = 6 746 010) in Sweden ≥ 18 years of age spanning from 1997 to 2018, with 116 175 995 person years of follow-up. The outcome was time to first occurrence of sepsis. The following variables were included in the analysis: sociodemographic factors (age, sex, income, education, marital status, region of residency, and country of origin), severe mental disorders (schizophrenia and bipolar disorders), and Charlson Comorbidity Index. Interaction tests were conducted. A total of 161 558 individuals were diagnosed with sepsis during the study period, corresponding to an incidence rate of 13.9 per 10 000 person years (95% CI: 13.8 - 14.0). The main findings were that male sex, high age, low education, and comorbid conditions were positively associated with sepsis, after adjustments for the other covariates. Being aged 80 years and above yielded a HR of 18.19 (95% CI: 17.84 - 18.55) and the effect of high age was more than twice as high in men than in women. In conclusion, this large nationwide cohort found that several sociodemographic factors and comorbid conditions were independently associated with sepsis and men were more affected by higher age than women. These findings can help improve sepsis awareness and preventive work in risk groups.
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BACKGROUND: We aim to estimate population-attributable fractions (PAF) for 13 comorbidities potentially predisposing to hepatobiliary cancer of hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cancers of the intrahepatic and extrahepatic bile ducts (ICC and ECC), and ampullary cancer. METHODS: Patients were identified from the Swedish Inpatient Register from 1987 to 2018 and cancers from the Swedish Cancer Registry from 1997 through 2018. PAFs were calculated for each comorbidity-associated cancer using a cohort study design. RESULTS: For male HCC, the major individual comorbidities (PAF > 10) were diabetes, alcohol-related liver disease, and hepatitis C virus infection. For female HCC, diabetes and autoimmune diseases were important contributors. For female GBC, gallstone disease was an overwhelming contributor, with a PAF of 30.57%, which was also important for men. The overall PAF for male ICC was almost two times higher than the female one. For ECC and ampullary cancer, infection of bile ducts was associated with the highest PAF. CONCLUSIONS: The 13 comorbidities accounted for 50% or more of the potential etiological pathways of each hepatobiliary cancer except female ICC. The underlying convergent mechanism for these cancers may be chronic inflammation lasting for decades and thus offering possibilities for intervention and disease monitoring.
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BACKGROUND: Squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the uterine cervix have distinct biological behaviors and different treatment responses. Studies on immune features and genomic profiling of these two pathologic types were limited and mainly focused on small patient cohorts. METHODS: From 2014 to 2021, 336 (254 SCC vs. 82 AC) cervical cancer patients who were diagnosed/treated in 7 medical centers in China were enrolled in the study. Next-generation sequencing of 425 cancer-relevant genes was performed on tumor tissues and liquid biopsies. Somatic alterations and immune response-related biomarkers were analyzed. Patient prognosis and immune infiltration were analyzed using data from The Cancer Genome Atlas (TCGA). RESULTS: AC tended to have more immunotherapy resistance-related STK11 alterations (P = 0.039), a higher proportion of microsatellite instability (P = 0.21), and more actionable mutations (P = 0.161). In contrast, higher tumor mutational burdens (TMB; P = 0.01), a higher proportion of TMB-high patients (P = 0.016), and more PD-L1-high patients (P = 0.0013) were observed in SCC. Multiple genetic alterations and aberrant signaling pathways were specifically enriched in AC (e.g., TP53, KRAS, ERBB2, and ARID1A alterations) or SCC (e.g., PIK3CA, FBXW7, EP300, and BAP1 mutations). Notably, AC-enriched genetic changes were significantly associated with decreased infiltrations of various B cells, T cells, and dendritic cells, whereas SCC-associated molecular features tended to be associated with increased CD4+ T cell infiltrations. CONCLUSIONS: This was the first multi-center study revealing the immunologic and genomic features between SCC and AC in Chinese patients with cervical cancer. Our findings have illustrated the difference in genetic profiles of those two cervical cancer subtypes, which may suggest the possibility of differential treatment regimens, with better immunotherapy efficacy in SCC and targeted therapy options more favorable in AC.