Purpose
The aim of this study was to describe the rate of amenorrhea in women treated with transcervical endometrial resection (TCER) or radiofrequency endometrial ablation combined with ...levonorgestrel intrauterine contraceptive device (LNG-IUD) six months post-operatively.
Methods
The study was performed as a prospective cohort study. All patients were included at four gynecological centers in Region of Southern Denmark. In total, 162 women referred due to menorrhagia, metrorrhagia or menometrorrhagia and offered TCER or radiofrequency endometrial ablation in combination with or without LNG-IUD included during November 2018 to June 2021 at the women’s own discretion and without any cost (covered by the hospital). Data were analyzed using a multivariate regression model.
Results
In total, 58 women were offered TCER and 31 (53.4%) combined treatment with TCER + LNG-IUD. Among 104 women who received radiofrequency endometrial ablation, 46 (44.2%) underwent combined treatment with LNG-IUD. The incidence of amenorrhea was 26% among women who underwent treatment with TCRE and 52% when treated with TCER + LNG-IUD (adjusted OR 5.16; 95% CI 1.35–19.6;
P
< 0.016). Radiofrequency endometrial ablation was followed by a 41% incidence of amenorrhea, and when radiofrequency endometrial ablation was combined with LNG-IUD, the incidence of amenorrhea was 63% (adjusted OR 2.15; 95% CI 0.86–5.37;
P
< 0.1). We observed no statistically significant differences when comparing the groups across.
Conclusion
Our study suggests that the combination of TCER or radiofrequency endometrial ablation with LNG-IUD was superior to TCER. However, the combined treatment of radiofrequency endometrial ablation with LNG-IUD did not reach statistical significance. Further studies are needed to evaluate the effects of different ablation techniques on the amenorrhea rate.
Objectives:
Extraosseous plasmacytoma (EOP) is a rare plasma cell neoplasm that tends to convert to plasma cell myeloma (PCM) in about 11% to 35% of cases. It has a predilection for the upper ...respiratory tract, prototypically affecting the nasal cavity and paranasal sinuses. Contemporary first-line treatment is radiotherapy, with more recent studies showing an added benefit of combining radiation with surgery. In this cohort study, we aimed to examine clinical presentation, treatment, and prognosis for all patients nationwide from 1980 through 2017. Furthermore, we determined the size and extension of tumors, investigating the rate at which minimally invasive surgery would have been possible.
Methods:
Patients were found in the national pathology registry, and all biopsies were collected for pathology review by a hematopathologist. We performed survival statistics for overall survival (OS), progression-free survival (PFS), and the cumulative incidence of conversion to PCM.
Results:
Twenty-three patients were included. The median age was 65, and patients were primarily men (78%). Tumors were located in either the nasal cavity (57%), maxillary sinus (39%), or sphenoid sinus (4%). In most cases, the tumor was <5 cm (65%) without extension to adjacent structures (60%). The national incidence was 0.02/100,000 person-years, the median symptom duration until diagnosis was 5 months, and none of the patients presented with contiguous spread to regional lymph nodes. Stand-alone radiotherapy was the predominant treatment (61%). In the entire cohort, one patient died from the initial disease, and six patients died from either relapse of EOP or PCM. The 5-year OS, PFS, and conversion rate to PCM were 78%, 56%, and 23%, respectively.
Conclusion:
SN-EOP responds well to radiotherapy, but relapse and conversion to PCM were not uncommon and entailed a poor prognosis. Most tumors were endoscopically resectable and non-invasive, making the majority of tumors suitable for surgery as an addition to radiation.
Compared to Asian and Latin American populations, sinonasal NK- or T-cell lymphoma is rare in Europe. All patients with sinonasal NK- or T-cell lymphoma in Denmark from 1980 to 2017 were validated ...histologically, and the disease behavior and demographics were extracted from medical records and national registries. Prognostic factors associated with mortality were determined using survival statistics. We included 56 patients: 40 extranodal NK/T-cell lymphoma (nasal type) (ENKTCL) and 16 peripheral T-cell lymphoma (not otherwise specified) (PTCL). The median age was 66, and most patients were male (72%). The ENKTCL and PTCL 5-year overall survival was 48% and 50%, respectively; progression-free survival was 38% for both. With ENKTCL, stage and performance status increased mortality significantly (HR = 8.6; p < 0.001 and HR = 4.23; p = 0.04). In conclusion, disseminated disease had a dismal outcome and the onset of ENKTCL in this ethnically homogeneous European cohort was about a decade later than reported in Asian populations.
Various strategies have been used to induce lifestyle changes to reduce ischaemic heart disease (IHD) with various successes. The aim of Inter99 is to assess the effect on IHD incidence of ...individually tailored non-pharmacological intervention on lifestyle using a newly developed computer-based health educational tool. The article describes the study and baseline results.
From a population of 61,301 individuals two random samples (high intensity intervention group (A), n = 11,708; low intensity intervention group (B), n = 1308) are screened to assess their absolute risk of IHD. Those at high risk receive individual lifestyle counselling. Individuals in group A are furthermore offered lifestyle counselling in groups on smoking cessation or physical activity/diet over a 6-month period. Individuals in group B are referred to their GP. High-risk persons are re-counselled after 1 and 3 years and the whole group is re-invited after 5 years. The remaining 48,285 (group C) are followed by questionnaire. The total population is followed through central registers. Intermediate end-points are changes in lifestyle, cholesterol, blood pressure and body mass index. Final end-point is reduction in incidence of IHD.
The randomization leads to comparable groups. Participation rate was 52.5%. A total of 60% fulfilled the predetermined criteria for being at high risk for developing IHD. After an individual lifestyle counselling 41% accepted group-based counselling.
This large randomized population based trial discloses a noticeable need for and acceptance of lifestyle intervention in the general population.
The mucus overlying mucosal epithelial surfaces presents not only a biological barrier to the penetration of potential pathogens, but also therapeutic modalities including RNAi-based nanocarriers. ...Movement of nanomedicines across the mucus barriers of the gastrointestinal mucosa is modulated by interactions of the nanomedicine carriers with mucin glycoproteins inside the mucus, potentiated by the large surface area of the nanocarrier. We have developed a fluorescence activation-based reporter system showing that the interaction between polyanionic mucins and the cationic chitosan/small interfering RNA (siRNA) nanocarriers (polyplexes) results in the disassembly and consequent triggered release of fluorescent siRNA. The quantity of release was found to be dependent on the molar ratio between chitosan amino groups and siRNA phosphate groups (NP ratio) of the polyplexes with a maximal estimated 48.6% release of siRNA over 30 min at NP 60. Furthermore, a microfluidic in vitro model of the gastrointestinal mucus barrier was used to visualize the dynamic interaction between chitosan/siRNA nanocarriers and native purified porcine stomach mucins. We observed strong interactions and aggregations at the mucin-liquid interface, followed by an NP ratio dependent release and consequent diffusion of siRNA across the mucin barrier. This work describes a new model of interaction at the nanocarrier-mucin interface and has important implications for the design and development of nucleic acid-based nanocarrier therapeutics for mucosal disease treatments and also provides insights into nanoscale pathogenic processes.
Autosomal dominant inheritance of congenital nephrogenic diabetes insipidus (CNDI) is rare and usually caused by variations in the AQP2 gene. We have investigated the genetic and molecular background ...underlying symptoms of diabetes insipidus (DI) in a Swedish family with autosomal dominant inheritance of the condition.
The proband and her father were subjected to water deprivation testing and direct DNA sequencing of the coding regions of the AQP2 and AVP genes. Madin-Darby canine kidney (MDCK) cells stably expressing AQP2 variant proteins were generated by lentiviral gene delivery. Localization of AQP2 variant proteins in the cells under stimulated and unstimulated conditions was analyzed by means of immunostaining and confocal laser scanning microscopy. Intracellular trafficking of AQP2 variant proteins was studied using transient expression of mutant dynamin2-K44A-GFP protein and AQP2 variant protein phosphorylation levels were assessed by Western blotting analysis.
Clinical and genetic data suggest that the proband and her father suffer from partial nephrogenic DI due to a variation (g.4807C > T) in the AQP2 gene. The variation results in substitution of arginine-254 to tryptophan (p.R254W) in AQP2. Analysis of MDCK cells stably expressing AQP2 variant proteins revealed disabled phosphorylation, impaired trafficking and intracellular accumulation of AQP2-R254W protein. Notably, blocking of the endocytic pathway demonstrated impairment of AQP2-R254W to reach the cell surface.
Partial CNDI in the Swedish family is caused by an AQP2 variation that seems to disable the encoded AQP2-R254W protein to reach the subapical vesicle population as well as impairing its phosphorylation at S256. The AQP2-R254W protein is thus unable to reach the plasma membrane to facilitate AVP mediated urine concentration.
Lymphomas of the nasal cavity and paranasal sinuses (NPS) are rare. Knowledge on sinonasal B‐cell lymphoma (SNBCL) primarily comes from case series or single‐center studies on small cohorts. We ...sought to determine the subtype distribution, clinical characteristics, disease behavior, and prognosis on a nationwide scale, with an emphasis on prognostic factors for the most common sinonasal lymphoma, primary sinonasal diffuse large B‐cell lymphoma (PSDLBCL). We collated all data from medical records and national databases on patients registered with SNBCL from 1980 through 2018 in the national pathology registry and collected all tissue samples for validation of diagnosis. We included 205 patients and found 10 different subtypes of lymphoma. Diffuse large B‐cell lymphoma (DLBCL) was the predominant subtype (80%). The incidence of SNBCL was 0.14/100,000 person‐years. The five‐year progression‐free survival (PFS) and overall survival rates for PSDLBCL were 50% and 56%, respectively. For PSDLBCL, Rituximab showed a statistically significant effect (Hazard Ratio 0.22, p < 0.001), whereas consolidative radiotherapy combined with immunochemotherapy was of limited value (PFS, p = 0.93). When treatment failure occurred, DLBCL showed a distinct pattern of recurrence/dissemination to the NPS, skin, breast, central nervous system (CNS), and/or testis. Collectively, DLBCL comprised a clear majority of SNBCLs, although nine other subtypes were represented. Data showed that immunochemotherapy increased survival for PSDLBCL and that the addition of radiotherapy did not benefit patients. Furthermore, treatment failure for sinonasal DLBCL showed a possible common pathogenesis with primary extranodal lymphomas of specific locations (e.g., CNS, skin, breast, and testis).
Background Due to marked regional differences in the incidence of coronary heart disease (CHD) in Europe, the recommendation by the European Society of Cardiology to use the Coronary Risk Chart based ...on data from the Framingham Heart Study, could be questioned. Methods Data from two population studies (The Glostrup Population Studies, n = 4757, the Framingham Heart Study, n = 2562) were used to examine three different levels of cross-validation. The first level of examination was whether a risk-score developed from one sample adequately ordered the risk of participants in the other sample, using the Area Under a Receiver Operating Characteristic (AUROC) curve. The second level compared the magnitude of coefficients in logistic models in the two studies; while the third level tested whether the level of risk of CHD death in one sample could be estimated based on a risk function from the other sample. Result Coronary heart disease mortality was 515 per 100 000 person-years in Framingham and 311 per 100 000 person-years in Glostrup. The AUROC curve was between 75% and 77% and regardless of which risk-score was used. Logistic coefficients did not differ significantly between studies. The Framingham risk-score significantly overestimated the risk in the Glostrup sample and the Glostrup risk-score underestimated in the Framingham sample. Conclusion Using this Framingham risk-score on a Danish population will lead to a significant overestimation of coronary risk. The validity of risk-scores developed from populations with different incidence of the disease should preferably be tested prior to their application.
Options for the prevention of cardiovascular disease, the greatest global cause of death, include population preventive measures (the Rose approach), or specifically seeking out and managing ...high-risk cases. However, the likely benefit of a population approach has been recently questioned.
To compare the estimated effects of population strategies at varying levels of population-wide risk factor reduction and high-risk strategies at varying rates of screening uptake on cardiovascular disease mortality.
Data (of 109 954 participants) were pooled from six European general population cohort studies the high-risk cohorts from the SCORE (Systematic COronary Risk Evaluation) dataset. The effects of various population and high-risk strategies for the reduction of risk factors were estimated by calculating the change in 10-year risk of cardiovascular disease mortality (SCORE risk) before and after the particular intervention. Risk factors studied were: total cholesterol, blood pressure and smoking.
At population level, if a 10-year reduction of blood cholesterol level of 10%, a BP reduction of 10% and a 10% reduction in the prevalence of smoking is considered possible, then 9125 lives per million of the population would be saved over 10 years. In contrast, an approach that treats all high-risk individuals with a polypill containing statin, three half-dose antihypertensives and aspirin, with a 20-80% uptake, would save 1861-7452 lives per million. However, the high-risk estimates are very optimistic, as their achievement would require complete compliance.
High-risk and population strategies are complementary. These estimates of the benefits of each may be useful to health planners, when combined with their local knowledge. Recently, benefits of population strategies have been underestimated.
Estimation of cardiovascular disease risk, using SCORE (Systematic COronary Risk Evaluation) is recommended by European guidelines on cardiovascular disease prevention. Risk estimation is inaccurate ...in older people. We hypothesized that this may be due to the assumption, inherent in current risk estimation systems, that risk factors function similarly in all age groups. We aimed to derive and validate a risk estimation function, SCORE O.P., solely from data from individuals aged 65 years and older.
20,704 men and 20,121 women, aged 65 and over and without pre-existing coronary disease, from four representative, prospective studies of the general population were included. These were Italian, Belgian and Danish studies (from original SCORE dataset) and the CONOR (Cohort of Norway) study. The variables which remained statistically significant in Cox proportional hazards model and were included in the SCORE O.P. model were: age, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, smoking status and diabetes. SCORE O.P. showed good discrimination; area under receiver operator characteristic curve (AUROC) 0.74 (95% confidence interval: 0.73 to 0.75). Calibration was also reasonable, Hosmer-Lemeshow goodness of fit test: 17.16 (men), 22.70 (women). Compared with the original SCORE function extrapolated to the ≥65 years age group discrimination improved, p = 0.05 (men), p < 0.001 (women). Simple risk charts were constructed. On simulated external validation, performed using 10-fold cross validation, AUROC was 0.74 and predicted/observed ratio was 1.02.
SCORE O.P. provides improved accuracy in risk estimation in older people and may reduce excessive use of medication in this vulnerable population.
PDF
