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NaI(Tl) based scintillation detectors have become a staple in the field of direct dark matter searches, with the DAMA-LIBRA experiment being the standout for its reported observation of an annually modulating WIMP-like signal which is in direct contrast with other results. In order to accurately calibrate the energies of WIMP-induced nuclear recoil signals, precise measurements of the quenching factor of the NaI crystals are essential for each of these experiments, as it is well established that electron recoils and nuclear recoils have dissimilar scintillation light yields. In this contribution, we present first preliminary results of an ongoing systematic study that has been carried out by the COSINUS collaboration and Duke University to measure the quenching factor of Na recoils. Five ultra-pure NaI crystals, manufactured by the Shanghai Institute for Ceramics, each of which have varying Tl dopant concentrations, were irradiated with a mono-energetic neutron beam at the Triangle Universities National Laboratory, North Carolina, USA to extract the quenching factor values in the low recoil energies of 1-30keV$_{nr}$.

The increasing statistical significance of the DAMA/LIBRA annual modulation signal is a cause for tension in the field of dark matter direct detection. The COSINUS experiment aims at a model-independent cross-check of the DAMA/LIBRA signal claim, using NaI crystals operated as cryogenic scintillating calorimeters at millikelvin temperatures. Such a setup enables measurement of phonon and scintillation light signals via Transition Edge Sensors (TESs) and allows particle discrimination on an event-by-event basis. The non-standard properties of NaI cause an obstacle when attaching a TES directly onto the surface of the crystal. This can be overcome with the ``remoTES'' design, where the TES is attached to an external wafer crystal. We present the results from a first successful operation of NaI and other crystals as cryogenic calorimeters with the remoTES design.

Antioestrogen treatment by tamoxifen is a well-established adjuvant therapy for oestrogen receptor-alpha (ERα) positive breast cancer. Despite ERα expression some tumours do not respond to tamoxifen and we therefore delineated the potential link between the cell cycle regulator and ERα co-factor, cyclin D1, and tamoxifen response in a material of 167 postmenopausal breast cancers arranged in a tissue array. The patients had been randomised to 2 years of tamoxifen treatment or no treatment and the median follow-up time was 18 years. Interestingly in the 55 strongly ERα positive samples with moderate or low cyclin D1 levels, patients responded to tamoxifen treatment whereas the 46 patients with highly ERα positive and cyclin D1 overexpressing tumours did not show any difference in survival between tamoxifen and no treatment. Survival in untreated patients with cyclin D1 high tumours was slightly better than for patients with cyclin D1 low/moderate tumours. However, there was a clearly increased risk of death in the cyclin D1 high group compared to an age-matched control population. Our results suggest that cyclin D1 overexpression predicts for tamoxifen treatment resistance in breast cancer, which is line with recent experimental data using breast cancer cell lines and overexpression systems. [ABSTRACT FROM AUTHOR]

A response by S. Borgquist et al. to a letter to the editor about their article "Oestrogen Receptors α and β Show Different Associations to Clinicopathological parameters and Their Co-Expression Might Predict a Better Response to Endocrine Treatment in Breast Cancer" in the 2008 issue is presented.

Abstract: Keiner, M, Kierot, M, Stendahl, M, Brauner, T, and Suchomel, TJ. Maximum strength and power as determinants of match skating performance in elite youth ice hockey players. J Strength Cond Res 38(6): 1090-1094, 2024-Maximum strength has a strong influence on speed-strength performances such as sprints and jumps. Important for sports practice is whether these findings are also reflected in game performance. Therefore, the aim of this study was to explore the influence of maximum strength and power performance on linear on-ice skating performance in testing and during game play. A cross-sectional study was conducted, and 24 highly trained male youth ice hockey players participated. Jump performances (countermovement jump [CMJ], drop jumps), maximum strength (1 repetition maximum [1RM] squat and isometric trap bar pull [ITBP]), and on-ice linear sprints (15 m [LS15], 30 m [LS30], flying 15 m [FLY15]) were measured. Match performances (among others: peak skating speed) were collected of 4 regular league games using a local positioning system. Correlation coefficient and explained variance were calculated ( ρ ≤ 0.05). Correlations between maximum strength and jump with on-ice linear sprint performance showed 1-35% explained variance. Correlations between "off ice" test (CMJ, relative 1RM) and game data (peak skating speed) showed 22-30% explained variance, respectively, while ITBP and DJ missed significant level. Between linear sprint and game performance showed 15-59% explained variance. In this study, a clear influence of 1RM in squatting and CMJ performance on on-ice linear sprint as well as in-game peak skating speed was observed. These findings show that strength and jumping performance can be valuable tests within a comprehensive test battery and indicate the relevance of strength and jumping tasks within the regular exercise program to improve in-game skating performance., (Copyright © 2024 National Strength and Conditioning Association.)

In ice hockey, speed strength is one of the major physical key performance indicators, which is significantly influenced by maximum strength. The objective of this study was to evaluate the age-dependent relationship of off-ice maximum strength and vertical jump performance with on-ice linear sprint performance, considering age and performance level. Ninety-one male youth and adult professional ice hockey players (age: 19.3 ± 5.49 years) were recruited and divided into four age groups: under 16, 18, 21 years old and professional elite players (Pro) (i.e., > 21 years). They were tested in maximal isometric strength, squat jump (loaded and unloaded), countermovement jump and on-ice sprint performance (15 m and 30 m linear sprint; 15 m flying linear sprint). Statistical analysis revealed that on-ice sprint performance correlated with isometric strength performance (r = |0.34|-|0.63|) and with off-ice jump performance (r = |0.61|-|0.77|) without an influence of age group or performance level. However, performance differed between age groups and performance level, the largest differences being found between the youngest age group (U16) and the Pro group (g = 0.966-3.281). The present study shows that maximum strength influences on-ice sprint performances in ice hockey players, as well as performance differences between age groups and professional players. Strength and jumping performance should therefore be included in regular performance testing in ice hockey. Since performance differences are observed for almost all strength and speed-strength performances of the youth teams to the Pros, training of these variables is strongly recommended to improve in the transition phase from junior to elite level., Competing Interests: The authors declare no conflict of interest., (Copyright © Biology of Sport 2024.)

Background: Several studies have demonstrated an increased risk of severe coronavirus disease 2019 (COVID-19) in chronic kidney disease (CKD) patients. However, few have investigated the impact of CKD stage and dialysis modality. The primary aim of this study was to investigate the association between CKD stage, dialysis modality and risk of severe COVID-19. Secondly, we aimed to study the impact of comorbidities and drugs on the risk of severe COVID-19 in the CKD population., Methods: This nationwide observational study was based on data from the Swedish Renal Registry and three other national registries. Patients with non-dialysis CKD stage 3b-5 or dialysis on 1 January 2020 were included and followed until 31 December 2021. The primary outcome was COVID-19 hospitalization; the secondary outcome was COVID-19 mortality. Associations were investigated using logistic regression models, adjusting for confounders., Results: The study population comprised 7856 non-dialysis CKD patients and 4018 dialysis patients. The adjusted odds ratios (aOR) for COVID-19 hospitalization and mortality were highest in the dialysis group [aOR 2.24, 95% confidence interval (CI) 1.79-2.81; aOR 3.10, Cl 95% 2.03-4.74], followed by CKD 4 (aOR 1.33, 95% CI 1.05-1.68; aOR 1.66, Cl 95% 1.07-2.57), as compared with CKD 3b. No difference in COVID-19 outcomes was observed between patients on hemodialysis and peritoneal dialysis. Overall comorbidity burden was one of the strongest risk factors for severe COVID-19 and the risk was also increased in patients prescribed insulin, proton pump inhibitors, diuretics, antiplatelets or immunosuppressants., Conclusions: Worsening CKD stage and comorbidity are independent risk factors for severe COVID-19 in the Swedish CKD population., Competing Interests: No potential conflicts of interests relevant to this article were declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD). This paper is a summary of the ERA Registry Annual Report 2021, including a comparison across treatment modalities., Methods: Data was collected from 54 national and regional registries from 36 countries, of which 35 registries from 18 countries contributed individual patient data and 19 registries from 19 countries contributed aggregated data. Using this data, incidence and prevalence of KRT, kidney transplantation rates, survival probabilities and expected remaining lifetimes were calculated., Result: In 2021, 533.2 million people in the general population were covered by the ERA Registry. The incidence of KRT was 145 per million population (pmp). In incident patients, 55% were 65 years or older, 64% were male, and the most common primary renal disease (PRD) was diabetes (22%). The prevalence of KRT was 1040 pmp. In prevalent patients, 47% were 65 years or older, 62% were male, and the most common PRDs were diabetes and glomerulonephritis/sclerosis (both 16%). On 31 December 2021, 56% of patients received haemodialysis, 5% received peritoneal dialysis, and 39% were living with a functioning graft. The kidney transplantation rate in 2021 was 37 pmp, a majority coming from deceased donors (66%). For patients initiating KRT between 2012-2016, 5-year survival probability was 52%. Compared to the general population, life expectancy was 65% and 68% shorter for males and females receiving dialysis, and 40% and 43% shorter for males and females living with a functioning graft., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: Patients on kidney replacement therapy (KRT) have been identified as a vulnerable group during the coronavirus disease 2019 (COVID-19) pandemic. This study reports the outcomes of COVID-19 in KRT patients in Sweden, a country where patients on KRT were prioritized early in the vaccination campaign., Methods: Patients on KRT between January 2019 and December 2021 in the Swedish Renal Registry were included. Data were linked to national healthcare registries. The primary outcome was monthly all-cause mortality over 3 years of follow-up. The secondary outcomes were monthly COVID-19-related deaths and hospitalizations. The results were compared with the general population using standardized mortality ratios. The difference in risk for COVID-19-related outcomes between dialysis and kidney transplant recipients (KTRs) was assessed in multivariable logistic regression models before and after vaccinations started., Results: On 1 January 2020, there were 4097 patients on dialysis (median age 70 years) and 5905 KTRs (median age 58 years). Between March 2020 and February 2021, mean all-cause mortality rates increased by 10% (from 720 to 804 deaths) and 22% (from 158 to 206 deaths) in dialysis and KTRs, respectively, compared with the same period in 2019. After vaccinations started, all-cause mortality rates during the third wave (April 2021) returned to pre-COVID-19 mortality rates among dialysis patients, while mortality rates remained increased among transplant recipients. Dialysis patients had a higher risk for COVID-19 hospitalizations and death before vaccinations started {adjusted odds ratio [aOR] 2.1 [95% confidence interval (CI) 1.7-2.5]} but a lower risk after vaccination [aOR 0.5 (95% CI 0.4-0.7)] compared with KTRs., Conclusions: The COVID-19 pandemic in Sweden resulted in increased mortality and hospitalization rates among KRT patients. After vaccinations started, a distinct reduction in hospitalization and mortality rates was observed among dialysis patients, but not in KTRs. Early and prioritized vaccinations of KRT patients in Sweden probably saved many lives., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: The aim of this study was to describe the trends in the incidence, prevalence and survival of patients on kidney replacement therapy (KRT) for end-stage kidney disease (ESKD) across Europe from 2008 to 2017., Methods: Data from renal registries in 9 countries and 16 regions that provided individual patient data to the ERA Registry from 2008 to 2017 were included. These registries cover 34% of the general population in Europe. Crude and standardized incidence and prevalence per million population (pmp) were determined. Trends over time were studied using Joinpoint regression. Survival probabilities were estimated using Kaplan-Meier analysis and hazard ratios (HRs) using Cox regression analysis., Results: The standardized incidence of KRT was stable [annual percentage change (APC): -1.48 (-3.15; 0.21)] from 2008 (146.0 pmp) to 2011 (141.6 pmp), followed by a slight increase [APC: 1.01 (0.43; 1.60)] to 148.0 pmp in 2017, although trends in incidence varied across countries. This increase was primarily due to a rise in the incidence of KRT in men older than 65 years. Moreover, as a cause of kidney failure, diabetes mellitus is increasing. The standardized prevalence increased from 2008 (990.0 pmp) to 2017 (1166.8 pmp) [APC: 1.82 (1.75; 1.89)]. Patient survival on KRT improved in the time period 2011-13 compared with 2008-[adjusted HR: 0.94 (0.93; 0.95)]., Conclusion: This study showed an overall increase in the incidence and prevalence of KRT for ESKD as well as an increase in the KRT patient survival over the last decade in Europe., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Gluten immunogenic peptides (GIP) in feces and/or urine have recently been proposed as a sensitive and specific marker to detect ongoing gluten intake. Here, we compared GIP with the Celiac Disease Adherence Test (CDAT), a simple validated self-administered questionnaire that measures adherence to gluten-free diet (GFD). Of 70 subjects (59 women), six were classified as non-adherent by fecal GIP (mean 0.23 µg/g, standard deviation 0.08, range 0.082-0.319), including five classified as non-adherent by CDAT. GFD adherence was significantly higher by GIP than CDAT (p < 0.001). Fecal GIP may be useful as a biomarker for ongoing gluten intake that is not possible to detect with current clinical methods to assess GFD adherence, and may play a role in the management of persistent gastrointestinal symptoms in celiac disease., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Data from the Swedish Renal Registry (SRR) show that during the period March 16, 2020 to March 15, 2021 0.4% of all renal transplant recipients and 3% of all dialysis patients died due to COVID-19 in Sweden. Of all registered deaths, 20% were attributed to COVID-19.  In the age group 50-59 years the risk ratio for COVID-19 related mortality was 16 (95% CI 6.5-38) among transplant recipients and 22 (95% CI 7.1-69) among dialysis patients, compared to the background population in the same age group. Excess mortality, compared to the five years preceding the pandemic, was 30% for transplant recipients and 8.7% for dialysis patients, compared to 7.7% for the entire Swedish population. Detailed reports were sent to SRR for 864 patients with confirmed COVID-19 infection representing 5.0% of all transplant recipients and 13% of all dialysis patients. The case fatality rate was 7.0% and 21% respectively.

Background: Strict adherence to a gluten-free diet usually leads to clinical and histological remission in celiac disease. Few studies have investigated the prevalence of persistent symptoms in a celiac population. We aimed to study the impact of gastrointestinal symptoms on general health in a large number of treated celiac patients, and describe the prevalence of persistent gastrointestinal symptoms and investigate associated factors., Methods: Adults with celiac disease filled out background questions, the Celiac Symptom Index (CSI) and the celiac disease adherence test (CDAT) in a web-based national survey. Participants who reported gastrointestinal symptoms during the previous week also recorded the gastrointestinal symptom rating scale-irritable bowel syndrome version (GSRS-IBS). Statistical analysis included chi-squared test, t -test, correlation, and linear regression., Results: Of 3834 participants (82% women; mean age 47 years), 54% reported gastrointestinal symptoms the previous week, and 30% of these had CSI score ≥45, indicative of the relatively poor quality of life (vs. 5% among those without gastrointestinal symptoms). The prevalence of persistent gastrointestinal symptoms (GSRS-IBS ≥30) was 40% and the most prominent symptoms were bloating (44%) and pain (37%). Age, sex, symptoms at the time of diagnosis, comorbidity, dietary adherence and CeD-specific health were significantly associated with gastrointestinal symptoms ( p  < .001)., Conclusion: In this national cross-sectional study among participants with celiac disease, persistent gastrointestinal symptoms were frequent, and were associated with a high symptom burden and reduced CeD-specific health. Several factors were associated with gastrointestinal symptoms, but more research is needed to find the cause of persistent symptoms in patients with celiac disease.

Rationale & Objective: Chronic kidney disease (CKD) is a global health problem with increasing prevalence. Several sex-specific differences have been reported for disease progression and mortality. Selection and survival bias might have influenced the results of previous cohort studies. The objective of this study was to investigate sex-specific differences of CKD progression and mortality among patients with CKD not receiving maintenance dialysis., Study Design: Observational cohort study., Setting & Participants: Adult patients with incident CKD glomerular filtration rate categories 3b to 5 (G3b-G5) identified between 2010 and 2018 within the nationwide Swedish Renal Registry-CKD (SRR-CKD)., Exposure: Sex., Outcomes: Time to CKD progression (defined as a change of at least 1 CKD stage or initiation of kidney replacement therapy [KRT]) or death. Repeated assessments of estimated glomerular filtration rate (eGFR)., Analytical Approach: CKD progression and mortality before KRT were assessed by the cumulative incidence function methods and Fine and Gray models, with death handled as a competing event. Sex differences in eGFR slope were estimated using mixed effects linear regression models., Results: 7,388 patients with incident CKD G3b, 18,282 with incident CKD G4, and 9,410 with incident CKD G5 were identified. Overall, 19.6 (95% CI, 19.2-20.0) patients per 100 patient-years progressed, and 10.1 (95% CI, 9.9-10.3) patients per 100 person-years died. Women had a lower risk of CKD progression (subhazard ratio [SHR], 0.88 [95% CI, 0.85-0.92]), and a lower all-cause (SHR, 0.90 [95% CI, 0.85-0.94]) and cardiovascular (SHR, 0.83 [95% CI, 0.76-0.90]) mortality risk. Risk factors related to a steeper decline in eGFR included age, sex, albuminuria, and type of primary kidney disease., Limitations: Incomplete data for outpatient visits and laboratory measurements and regional differences in reporting., Conclusions: Compared to women, men had a higher rate of all-cause and cardiovascular mortality, an increased risk of CKD progression, and a steeper decline in eGFR., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Therapeutic developments have contributed to markedly improved clinical outcomes in peritoneal dialysis (PD) during the 1990s and 2000s. We investigated whether recent advances in PD treatment are implemented in routine Swedish care and whether their implementation parallels improved patient outcomes., Methods: We conducted an observational study of 3122 patients initiating PD in Sweden from 2006 to 2015. We evaluated trends of treatment practices (medications, PD-related procedures) and outcomes [patient survival, major adverse cardiovascular events (MACEs), peritonitis, transfer to haemodialysis (HD) and kidney transplantation] and analysed associations of changes of treatment practices with changes in outcomes., Results: Over the 10-year period, demographics (mean age 63 years, 33% women) and comorbidities remained essentially stable. There were changes in clinical characteristics (body mass index and diastolic blood pressure increased), prescribed drugs (calcium channel blockers, non-calcium phosphate binders and cinacalcet increased and the use of renin-angiotensin system inhibitors, erythropoietin and iron decreased) and dialysis treatment (increased use of automated PD, icodextrin and assisted PD). The standardized 1- and 2-year mortality and MACE risk did not change over the period. Compared with the general population, the risk of 1-year mortality was 4.1 times higher in 2006-2007 and remained stable throughout follow-up. However, the standardized 1- and 2-year peritonitis rate decreased and the incidence of kidney transplantation increased while transfers to HD did not change., Conclusions: Over the last decade, treatment advances in PD patients were accompanied by a substantial decline in peritonitis frequency and an increased rate of kidney transplantations, while 1- and 2-year survival and MACE risk did not change., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Purpose: End-stage renal disease (ESRD) is a known risk factor for the development of renal cell carcinoma (RCC). This case-control study was performed to assess the risk in a nationwide cohort and evaluate tumor characteristics and survival in the ESRD-RCC population., Methods: In this study, 9,299 patients with RCC identified in the National Swedish Kidney Cancer Register from 2005 until 2014 and 93,895 matched controls were linked to the Swedish Renal Registry and the National Patient Register. ESRD was defined as chronic kidney disease stage 5, kidney transplantation or kidney dialysis 0-40 years before the diagnosis of RCC., Results: A total of 117 patients with ESRD and subsequent RCC were identified and compared with 9,087 patients with RCC. There was a 4.5-times increased risk for RCC among ESRD patients (95% CI = 3.6-5.6; p  < 0.001) compared to matched controls. Longer time with ESRD increased the risk of RCC (ESRD > 9 years, OR = 10.2, 95% CI = 7.0-14.8). The ESRD-RCC patients were younger ( p  = 0.002), had smaller tumors ( p  < 0.001) and had lower tumor stage ( p  = 0.045). The incidence of papillary and chromophobe RCC was higher and clear cell RCC lower among the ESRD patients ( p  < 0.001). The 5-year overall survival was 50% in ESRD-RCC patients and 63% in RCC-only patients ( p  < 0.05)., Conclusion: More than 9 years with ESRD increased the risk of developing RCC 10-times compared to individuals without ESRD and the tumors showed a different histopathological pattern. Despite a less advanced tumor stage at diagnosis, the overall survival in ESRD-RCC patients was lower compared to patients with RCC-only.

Background: The European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Registry collects data on kidney replacement therapy (KRT) via national and regional renal registries in Europe and countries bordering the Mediterranean Sea. This article summarizes the 2018 ERA-EDTA Registry Annual Report, and describes the epidemiology of KRT for kidney failure in 34 countries., Methods: Individual patient data on patients undergoing KRT in 2018 were provided by 34 national or regional renal registries and aggregated data by 17 registries. The incidence and prevalence of KRT, the kidney transplantation activity and the survival probabilities of these patients were calculated., Results: In 2018, the ERA-EDTA Registry covered a general population of 636 million people. Overall, the incidence of KRT for kidney failure was 129 per million population (p.m.p.), 62% of patients were men, 51% were ≥65 years of age and 20% had diabetes mellitus as cause of kidney failure. Treatment modality at the onset of KRT was haemodialysis (HD) for 84%, peritoneal dialysis (PD) for 11% and pre-emptive kidney transplantation for 5% of patients. On 31 December 2018, the prevalence of KRT was 897 p.m.p., with 57% of patients on HD, 5% on PD and 38% living with a kidney transplant. The transplant rate in 2018 was 35 p.m.p.: 68% received a kidney from a deceased donor, 30% from a living donor and for 2% the donor source was unknown. For patients commencing dialysis during 2009-13, the unadjusted 5-year survival probability was 42.6%. For patients receiving a kidney transplant within this period, the unadjusted 5-year survival probability was 86.6% for recipients of deceased donor grafts and 93.9% for recipients of living donor grafts., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: The recent years have witnessed significant therapeutic advances for patients on hemodialysis. We evaluated temporal changes in treatments practices and survival rates among incident hemodialysis patients., Methods: Observational study of patients initiating hemodialysis in Sweden 2006-2015. Trends of hemodialysis-related practices, medications, and routine laboratory biomarkers were evaluated. The incidence of death and major cardiovascular events (MACE) across calendar years were compared against the age-sex-matched general population. Via Cox regression, we explored whether adjustment for implementation of therapeutic advances modified observed survival and MACE risks., Results: Among 6,612 patients, age and sex were similar, but the burden of co-morbidities increased over time. The proportion of patients receiving treatment by hemodiafiltration, >3 sessions/week, lower ultrafiltration rate, and working fistulas increased progressively, as did use of non-calcium phosphate binders, cinacalcet, and vitamin D3. The standardized 1-year mortality decreased from 13.2% in 2006/07 to 11.1% in 2014/15. The risk of death decreased by 6% (HR 0.94, 95% CI 0.90-0.99) every two years, and the risk of MACE by 4% (HR 0.96; 0.92-1.00). Adjustment for changes in treatment characteristics abrogated these associations (HR 1.00; 0.92-1.09 for death and 1.00; 0.94-1.06 for MACE). Compared with the general population, the risk of death declined from 6 times higher 2006/2007 [standardized incidence rate ratio, sIRR 6.0 (5.3-6.9)], to 5.6 higher 2014/15 [sIRR 5.57 (4.8-6.4)]., Conclusions: Gradual implementation of therapeutic advances over the last decade was associated with a parallel reduction in short-term risk of death and MACE among hemodialysis patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Although patient-reported outcome measures (PROMs) are gaining increased interest in developing health care quality and are a useful tool in person-centered care, their use in routine care is still limited. The aim of this study is to describe the implementation and initial results of PROMs via the Swedish Renal Registry (SRR) on a national level., Methods: After testing and piloting the electronic PROM application, nationwide measures were carried out in 2017 for completing the RAND-36 questionnaire online or by paper in a wide range of chronic kidney disease (CKD) patients (Stages 3-5, dialysis and transplantation) through the SRR. Cross-sectional results during the first year were analyzed by descriptive statistics and stratified by treatment modality., Results: A total of 1378 patients from 26 of 68 renal units (39%) completed the questionnaire. The response rate for all participating hemodialysis units was 38.9%. The CKD patients had an impaired health profile compared with a Swedish general population, especially regarding physical functions and assessed general health (GH). Transplanted patients had the highest scores, whereas patients on dialysis treatment had the lowest scores. The youngest age group assessed their physical function higher and experienced fewer physical limitations and less bodily pain than the other age groups but assessed their GH and vitality (VT) relatively low. The oldest age group demonstrated the lowest health profile but rated their mental health higher than the other age groups. The older the patient, the smaller the difference compared with persons of the same age in the general population., Conclusions: Nationwide, routine collection of PROMs is feasible in Sweden. However, greater emphasis is needed on motivating clinical staff to embrace the tool and its possibilities in executing person-centered care. CKD patients demonstrate impaired health-related quality of life, especially regarding limitations related to physical problems, GH and VT/energy/fatigue., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: This article provides a summary of the 2013 European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report (available at http://www.era-edta-reg.org), with a focus on patients with diabetes mellitus (DM) as the cause of end-stage renal disease (ESRD)., Methods: In 2015, the ERA-EDTA Registry received data on renal replacement therapy (RRT) for ESRD from 49 national or regional renal registries in 34 countries in Europe and bordering the Mediterranean Sea. Individual patient data were provided by 31 registries, while 18 registries provided aggregated data. The total population covered by the participating registries comprised 650 million people., Results: In total, 72 933 patients started RRT for ESRD within the countries and regions reporting to the ERA-EDTA Registry, resulting in an overall incidence of 112 per million population (pmp). The overall prevalence on 31 December 2013 was 738 pmp (n = 478 990). Patients with DM as the cause of ESRD comprised 24% of the incident RRT patients (26 pmp) and 17% of the prevalent RRT patients (122 pmp). When compared with the USA, the incidence of patients starting RRT pmp secondary to DM in Europe was five times lower and the incidence of RRT due to other causes of ESRD was two times lower. Overall, 19 426 kidney transplants were performed (30 pmp). The 5-year adjusted survival for all RRT patients was 60.9% [95% confidence interval (CI) 60.5-61.3] and 50.6% (95% CI 49.9-51.2) for patients with DM as the cause of ESRD.

Background: Renal function is often estimated using one of several glomerular filtration rate (GFR) estimating equations. However, there is no consensus which estimating equation performs best in patients with advanced renal failure., Methods: We compared the performance of five different estimated GFR (eGFR) equations [Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease (CKD) Epidemiology collaboration (CKD-EPI) and Mayo Clinic and Lund-Malmö] with measured GFR (plasma iohexol clearance) in 2098 referred CKD patients with mGFR <30 mL/min/1.73 m(2)., Results: There were 398 patients with an mGFR ≤ 10 mL/min/1.73 m(2), 1974 with a measured GFR (mGFR) 11-20 mL/min/1.73 m(2) and 749 patients with mGFR 21-30 mL/min/1.73 m(2). Across the entire range, the median bias of eGFR was lowest for the Lund-Malmö equation (0.7 mL/min/1.73 m(2)), followed by the CKD-EPI (1.2 mL/min/1.73 m(2)), the MDRD (1.6 mL/min/1.73 m(2)), Mayo Clinic equation (1.7 mL/min/1.73 m(2)) and Cockcroft-Gault equation (4.6 mL/min/1.73 m(2)). The best accuracy within 30% of mGFR was also for Lund-Malmö (76%), while it was similar for CKD-EPI, MDRD and Mayo (65-67%). The Cockcroft-Gault had the worst accuracy of only ∼54%.The median bias was stable across mGFR categories, while the accuracy within 30% of mGFR became worse with decreasing mGFR. All equations performed best among patients with hereditary kidney diseases and tubulointerstitial disease. Accuracy was generally worse for patients >65 years of age and for those with diabetic nephropathy., Conclusions: In patients with advanced renal failure, the GFR-estimating equations show reasonably good performance on the population level. On the individual patient level, they are inaccurate, especially in elderly patients and those with diabetic nephropathy.

Background: Renal replacement therapy (RRT) incidence has increased significantly in Sweden during the past decades. This study analyses variations in time and regional trends in RRT incidence in Sweden, adjusted for age and gender, focusing on the impact change in incidence during the last decade., Methods: Using data from the Swedish Renal Registry (SRR) (21 counties in Sweden, total population 9 million), we identified all incident subjects starting RRT from 1991 through 2010. Only individuals alive following 90 days of RRT start were included. Gender- and age-specific standardized RRT incidences on an annual and regional basis were calculated, and differences between counties and variations over time were examined. We compared the overall age and gender-adjusted RRT incidence rates for Sweden by calendar year. Furthermore, we also calculated the age and gender-adjusted RRT incidence in each county during two time periods (1991-1999 versus 2000-2010)., Results: There were 20 172 new subjects treated with RRT between January 1991 and December 2010. The most common cause of end-stage renal disease (ESRD) was diabetes (24%) and hypertension/renal vascular disease (19%), followed by glomerulonephritis (16%). Sixty-four percent of new patients were male; the median age when commencing RRT was 66 years (10-90 percentiles; 39-80). The overall standardized RRT incidence reached its peak in 2000, and slowly decreased thereafter. A decrease in RRT incidence was observed over the study period in eight regions. The standardized RRT incidence varied between the different counties, from 0.82 to 1.19., Conclusions: Adjusted for demographic changes in the population, an overall decrease in RRT incidence was observed from the year 2000 onwards-suggesting that the previously reported steady increase in RRT incidence is coming to an end in Sweden. Noteworthy differences were found between counties and in 8 out of 21 counties, a decreased incidence of RRT was found. Further studies need to identify the factors that contribute to this decrease.

The cell-cycle regulating protein p27(Kip1) (p27) has dual roles by acting as both a cdk inhibitor and as an assembly factor for different cdk complexes. Loss of p27 has been linked to malignant features in tumours; however, the exact role of p27 deregulation in breast cancer regarding prognostic and treatment predictive information has not been fully clarified. We have evaluated p27 expression in 328 primary, Stage II breast cancers from premenopausal patients who had been randomised to either tamoxifen treatment or no adjuvant treatment after surgery. p27 was associated with the oestrogen receptor and cyclin D1, and p27 downregulation was associated with high proliferation. There was no association between recurrence-free survival (RFS) and p27 (HR = 0.800, 95% CI 0.523-1.222, p = 0.300), indicating that p27 is not a prognostic marker. The predictive value of p27 was analysed by comparing RFS in tamoxifen-treated and untreated patients in subgroups of low and high p27 expression (HR = 0.747, 95% CI 0.335-1.664, p = 0.474 and HR = 0.401, 95% CI 0.240-0.670, p < 0.001, respectively). Only patients with p27-high tumours benefited from tamoxifen (multivariate interaction analysis p = 0.034). Our study suggests that p27 downregulation is associated with tamoxifen resistance in premenopausal breast cancer but is not linked to impaired prognosis., (Copyright © 2010 UICC.)

Aims: The majority of all breast cancers are hormone responsive, traditionally defined by the expression of oestrogen receptor (ER) alpha and/or progesterone receptors. In contrast to ERalpha, the clinical significance of the relatively recently identified ERbeta is still unclear. This study aimed to define the relationship between ERbeta and clinicopathological parameters in a mixed cohort of breast cancer and, furthermore, to investigate the impact of ERbeta expression on disease outcome., Methods: The immunohistochemical expression of ERalpha and ERbeta was analysed in tissue microarrays containing a total number of 512 tumours with all incident breast cancers diagnosed at the Malmö University Hospital between 1988 and 1992., Results: 78% of the tumours were ERalpha positive and 50% were ERbeta positive. ERbeta correlated positively with ERalpha (p = 0.001). In contrast to ERalpha, ERbeta was not associated with any important clinicopathological variables. Furthermore, no overall prognostic significance could be demonstrated for ERbeta. In the ERalpha-positive subgroup, however, a low expression of ERbeta correlated with a decreased disease-free survival in patients receiving endocrine treatment (p = 0.003)., Conclusions: Although interrelated, ERalpha and ERbeta seem to be differentially associated to clinicopathological parameters, and this would support the fact that they might have different functions in vivo. Furthermore, ERbeta might be a predictive marker of response to endocrine therapy, although this needs to be confirmed in additional studies, preferably randomised trials.

Purpose: Tamoxifen has long been the drug of choice in adjuvant endocrine therapy of steroid hormone receptor-positive breast cancer, and it still remains important due to its well-documented beneficial effect. Hormone receptor status is often reported as "positive" or "negative" using 10% positive nuclei as a cutoff. In this study, we aimed to assess whether a further subclassification of hormone receptor status could enhance the treatment predictive value., Experimental Design: The immunohistochemical expression of estrogen receptor (ER) and progesterone receptor (PR) was quantified in tissue microarrays with tumors from 500 premenopausal breast cancer patients previously included in a randomized trial of adjuvant tamoxifen compared with an untreated control group., Results: Our findings show a gradually increasing tamoxifen effect in tumors with >10% ER-positive nuclei. However, when analyzing tamoxifen response according to various PR fractions, we found that it was primarily patients with tumors showing >75% PR-positive nuclei that responded to tamoxifen treatment, with an improved recurrence-free [relative risk, 0.42 (0.25-0.70); P = 0.001] as well as overall [relative risk, 0.49 (0.28-0.84); P = 0.010] survival., Conclusions: Adjuvant tamoxifen improved recurrence-free and overall survival for premenopausal patients with tumors showing >75% PR-positive nuclei. No effect could be shown in tumors with fewer PR-positive nuclei. The PR was a stronger predictor of treatment response than the ER. Based on these findings, we suggest the implementation of a fractioned rather than dichotomized immunohistochemical evaluation of hormone receptors in clinical practice, possibly with greater emphasis on the PR than the ER.

Cyclins D1 and A2 are cell cycle regulators that also have the ability to interact with the estrogen receptor (ER) and consequently interfere with antiestrogen treatment in breast cancer. Experimental data support this concept, but the clinical relevance needs to be further established. In this study, we evaluated cyclin D1 and A2 protein expression by immunohistochemistry and cyclin D1 gene (CCND1) amplification by fluorescence in situ hybridization in 500 primary breast cancers arranged in tissue microarrays. Patients had been randomized to 2 years of adjuvant tamoxifen or no treatment with a median follow-up of 14 years, allowing for subgroup analysis of treatment response defined by cyclin status. We found that both cyclin D1 and A2 protein overexpression was associated with an impaired tamoxifen response, although not significant in multivariate interaction analyses, whereas tamoxifen-treated patients with CCND1-amplified tumors had a substantially increased risk for disease recurrence after tamoxifen treatment in univariate analyses [relative risk (RR), 2.22; 95% confidence interval (95% CI), 0.94-5.26; P = 0.06] in contrast to non-amplified tumors (RR, 0.39; 95% CI, 0.23-0.65; P < 0.0001). Consequently, a highly significant interaction between tamoxifen treatment and CCND1 amplification could be shown regarding both recurrence-free survival (RR, 6.38; 95% CI, 2.29-17.78; P < 0.001) and overall survival (RR, 5.34; 95% CI, 1.84-15.51; P = 0.002), suggesting an agonistic effect of tamoxifen in ER-positive tumors. In node-positive patients, the disparate outcome according to gene amplification status was even more accentuated. In summary, our data implicate that despite a significant correlation to cyclin D1 protein expression, amplification status of the CCND1 gene seems a strong independent predictor of tamoxifen response, and possibly agonism, in premenopausal breast cancer.

Vascular endothelial growth factor (VEGF-A) is considered a prognostic indicator for clinical outcome in breast cancer. Conflicting results nevertheless exist and there is a need for larger studies including untreated patients in order to clarify the importance of tumor-specific VEGF-A regarding prognosis as well as potential links to predictive treatment information. VEGF-A and its receptor, vascular endothelial growth receptor 2 (VEGFR2), were therefore analyzed by immunohistochemistry in postmenopausal breast cancers enrolled in a clinical trial where patients were randomized to adjuvant tamoxifen treatment (n = 124) for 2 years or no treatment (n = 127) with a median follow-up of 18 years. The tumors were arranged in a tumor tissue microarray system enabling parallel analysis of the angiogenic factors and hormone receptor status. Tumor-specific expression of VEGFR2 correlated strongly with expression of VEGF-A and progesterone receptor (PR) negativity, whereas VEGF-A was not associated with hormone receptor status. Among patients with estrogen receptor (ER) positive (fraction > 10%) tumors, there was a statistically significant tamoxifen response in VEGF-A negative tumors at both 10-year and 18-year disease-free survival (DFS), contrasting to VEGF-A positive tumors who had no beneficial effect of tamoxifen. A treatment-interaction variable indicated a marked difference in tamoxifen response depending on VEGFA-status in terms of DFS at 10 and 18 years of follow-up, p = 0.046 and p = 0.039, respectively. VEGFR2 status did not yield significant predicitve information for tamoxifen response in patients with ER fraction > 10%, whereas in patients with ER fraction > 90% both VEGF-A and VEGFR2 status were associated with tamoxifen treatment effect.