Microbial Primer: Phase variation - survival and adaptability by generation of a diverse population.

Phase variation is defined as the rapid and reversible switching of gene expression, and typically occurs in genes encoding surface features in small genome bacterial pathogens. Phase variation has evolved to provide an extra survival mechanism in bacteria that lack multiple 'sense-and-respond' gene regulation systems. Many bacterial pathogens also encode DNA methyltransferases that are phase-variable, controlling systems called 'phasevarions' (phase-variable regulons). This primer will summarize the current understanding of phase variation, describing the role of major phase-variable factors, and phasevarions, in bacterial pathobiology.

Epigenetic Regulation of Driver Genes in Testicular Tumorigenesis.

In testicular germ cell tumor type II (TGCT), a seminoma subtype expresses an induced pluripotent stem cell (iPSC) panel with four upregulated genes, OCT4/POU5F1, SOX17, KLF4, and MYC, and embryonal carcinoma (EC) has four upregulated genes, OCT4/POU5F1, SOX2, LIN28, and NANOG. The EC panel can reprogram cells into iPSC, and both iPSC and EC can differentiate into teratoma. This review summarizes the literature on epigenetic regulation of the genes. Epigenetic mechanisms, such as methylations of cytosines on the DNA string and methylations and acetylations of histone 3 lysines, regulate expression of these driver genes between the TGCT subtypes. In TGCT, the driver genes contribute to well-known clinical characteristics and the driver genes are also important for aggressive subtypes of many other malignancies. In conclusion, epigenetic regulation of the driver genes are important for TGCT and for oncology in general.

Extended hard-X-ray emission in the inner few parsecs of the Galaxy.

The Galactic Centre hosts a puzzling stellar population in its inner few parsecs, with a high abundance of surprisingly young, relatively massive stars bound within the deep potential well of the central supermassive black hole, Sagittarius A* (ref. 1). Previous studies suggest that the population of objects emitting soft X-rays (less than 10 kiloelectronvolts) within the surrounding hundreds of parsecs, as well as the population responsible for unresolved X-ray emission extending along the Galactic plane, is dominated by accreting white dwarf systems. Observations of diffuse hard-X-ray (more than 10 kiloelectronvolts) emission in the inner 10 parsecs, however, have been hampered by the limited spatial resolution of previous instruments. Here we report the presence of a distinct hard-X-ray component within the central 4 × 8 parsecs, as revealed by subarcminute-resolution images in the 20-40 kiloelectronvolt range. This emission is more sharply peaked towards the Galactic Centre than is the surface brightness of the soft-X-ray population. This could indicate a significantly more massive population of accreting white dwarfs, large populations of low-mass X-ray binaries or millisecond pulsars, or particle outflows interacting with the surrounding radiation field, dense molecular material or magnetic fields. However, all these interpretations pose significant challenges to our understanding of stellar evolution, binary formation, and cosmic-ray production in the Galactic Centre.

Iridium thin-film coatings for the BabyIAXO hybrid X-ray optic.

Reflective coatings are an essential feature of X-ray telescopes. Their overall performance relies heavily on substrate compatibility and how well they conform to the optics assembly processes. We use X-ray reflectometry (XRR) to demonstrate the compatibility of shaping flat substrates coated with iridium, and show that specular and nonspecular reflectance before and after shaping is on par with traditional hot-slumped coated substrates. From 1.487 and 8.048keV measurements, we find that the substrates have rms roughness of 0.38nm and magnetron sputtered iridium deposits with rms surface roughness of 0.27-0.35nm. A hydrocarbon overlayer from atmospheric contamination is present with a thickness of 1.4-1.6nm and a density of 1.2-1.6g/cm3. Both the traditional hot slumped and the flat substrates undergoing post-coating shaping have a similar characteristic surface morphology and are equally well-suited for use with X-ray optics. Finally, we demonstrate by simulation the improved effective area achieved by using a low-Z overlayer, and illustrate the performance of a hybrid optic coated with optimized bilayers for a Primakoff axion spectrum emitted by the sun.

Maternal age and risk of cesarean section in women with induced labor at term-A Nordic register-based study.

INTRODUCTION: Over the last decades, induction of labor has increased in many countries along with increasing maternal age. We assessed the effects of maternal age and labor induction on cesarean section at term among nulliparous and multiparous women without previous cesarean section. MATERIAL AND METHODS: We performed a retrospective national registry-based study from Denmark, Finland, Iceland, Norway, and Sweden including 3 398 586 deliveries between 2000 and 2011. We investigated the impact of age on cesarean section among 196 220 nulliparous and 188 158 multiparous women whose labor was induced, had single cephalic presentation at term, and no previous cesarean section. Confounders comprised country, time-period, and gestational age. RESULTS: In nulliparous women with induced labor the rate of cesarean section increased from 14.0% in women less than 20 years of age to 39.9% in women 40 years and older. Compared with women aged 25-29 years, the corresponding relative risks were 0.60 (95% confidence interval [95% CI] 0.57 to 0.64) and 1.72 (95% CI 1.66 to 1.79). In multiparous induced women the risk of cesarean section was 3.9% in women less than 20 years rising to 9.1% in women 40 years and older. Compared with women aged 25-29 years, the relative risks were 0.86 (95% CI 0.54 to 1.37) and 1.98 (95% CI 1.84 to 2.12), respectively. There were minimal confounding effects of country, time-period, and gestational age on risk for cesarean section. CONCLUSIONS: Advanced maternal age is associated with increased risk of cesarean section in women undergoing labor induction with a single cephalic presentation at term without a previous cesarean section. The absolute risk of cesarean section is 3-5 times higher across 5-year age groups in nulliparous relative to multiparous women having induced labor.

Specimen-Specific Finite Element Models for Predicting Fretting Wear in Total Hip Arthroplasty Tapers.

Products from fretting wear and corrosion in the taper junction of total hip arthroplasty (THA) devices can lead to adverse local tissue reactions. Predicting damage as a function of design parameters would aid in the development of more robust devices. The objectives of this study were to develop an automated method for identifying areas of fretting wear on THA taper junctions, and to assess the predictive ability of a finite element model to simulate fretting wear in THA taper junctions. THA constructs were fatigue loaded, thus inducing damage on the stem taper. An automated imaging and analysis algorithm quantified fretting wear on the taper surfaces. Specimen-specific finite element models were used to calculate fretting work done (FWD) at the taper junction. Simulated FWD was correlated to imaged fretting wear. Results showed that the automated imaging approach identified fretting wear on the taper surface. Additionally, finite element models showed the greatest predictive ability for tapers exhibiting distal contact. Finite element models predicted an average of 30.3% of imaged fretting wear. With additional validation, the imaging and finite element techniques may be useful to manufacturers and regulators in the development and review of new THA devices.

The retropubic tension-free vaginal tape procedure-Efficacy, risk factors for recurrence and long-term safety.

INTRODUCTION: The retropubic tension-free vaginal tape has been the preferred method for primary surgical treatment of stress urinary incontinence and stress-dominated mixed urinary incontinence in women for more than 20 years. This study presents long-term safety and efficacy data and assesses risk factors for long-term recurrence. MATERIAL AND METHODS: In a case-series design we assessed a historical cohort of primary surgeries performed with the tension-free vaginal tape procedure in 596 women from 1998 to 2012 with follow up through 2015. Information from the medical records was transferred to a case report form comprising data on early and late complications and recurrence of urinary incontinence defined as bothersome stress urinary incontinence symptoms. All analyses were performed with SPSS using Pearson chi-square, survival and Cox regression analyses. RESULTS: After a 10-year follow up, mixed urinary incontinent women (hazard ratio 2.1, 95% confidence interval [CI] 1.4-3.0) had a significantly increased risk of recurrence of stress urinary incontinence symptoms compared with women with pure stress urinary incontinence as the indication for surgery. Overall cumulative cure rates after 1, 5 and 10 years were 92% (95% CI; 90%-94%), 79% (95% CI; 75%-83%) and 69% (95% CI; 63%-75%), respectively. Recurrent surgery (0.3%) and serious tape complications needing major surgical treatment (0.3%) were rare. Six patients (1.0%) had the tape cut due to urinary retention, and nine patients (1.5%) reported urinary retention more than 3 months after surgery. CONCLUSIONS: The tension-free vaginal tape procedure has a high long-term durability. Mixed urinary incontinence as an indication for surgery predicted long-term recurrence. Long-term complications were rare.

Corticosteroid injection is the best treatment in plantar fasciitis if combined with controlled training.

PURPOSE: Plantar fasciitis is a very common (lifetime incidence ~ 10%) and long-lasting injury with major impact on daily function. Combining corticosteroid injection and physical training (strength training and stretching) was hypothesized to result in a superior effect compared to each treatment separately. METHODS: A single blinded randomized controlled superiority trial conducted in 2013-2014 with a 2-year follow-up (end Sept 2016). 123 consecutive patients (20-65 years) referred to two study centers in Denmark: Institute of Sports Medicine, Bispebjerg Hospital, University of Copenhagen and a private rheumatology clinic with symptoms of plantar fasciitis, and ultrasound measured thickness above 4.0 mm were invited. 25 did not fulfill the inclusion criteria (mainly ultrasound criteria) and 8 refused participation. 90 patients were randomized (pulling sealed envelopes) to 3 groups: (1) 3 months strength training and stretching (n = 30), (2) corticosteroid injections with monthly intervals until thickness < 4.0 mm (maximum 3 injections) (n = 31), (3) combination of the two treatments (n = 29). During the 3 months intervention period load reduction was recommended (cushioning shoes and insoles and abstaining from running and jumping). The main outcome was improvement in Pain at function on a 100-mm VAS score and in Foot Function Index (FFI, range 0-230) at 6 months (Clinicaltrials.gov Identifier: NCT01994759). RESULTS: All groups improved significantly over time, but the combination of corticosteroid injection and training (strength training and stretching) had a superior effect at all time points. The mean difference between the combined treatment and training was 40 points in FFI (95% confidence interval (CI) 63-17 points, p < 0.001) and 20 mm for VAS function pain (CI 35-5 mm, p < 0.01). The mean difference between the combined treatment and corticosteroid injections only was 29 points in FFI (CI 52-7 points, p < 0.01) and 17 mm for VAS function pain (CI 32-2 mm, p < 0.05). All differences were clinically relevant. CONCLUSION: The best treatment for plantar fasciitis is the combination of corticosteroid injections and training (strength training and stretching). This combined treatment is superior both in the short- and in the longterm. Corticosteroid injections combined with controlled training are recommended as first line treatment in patients with plantar fasciitis. LEVEL OF EVIDENCE: 1.

Decreasing trends in number of depot medroxyprogesterone acetate starters in Norway - a cross-sectional study.

INTRODUCTION: In this study, we examined changes in depot medroxyprogesterone acetate (DMPA) prescriptions over a time-period when new professions started prescribing, and when the method gained some negative media attention. MATERIAL AND METHODS: The Norwegian Prescription Database provided data on hormonal contraception from 2006 through 2012. We estimated the annual number of DMPA users by calculating doses sold per day/1000 women and calculated, for each contraceptive method on annual basis, a proportion of defined daily doses of all hormonal contraceptives in five-year age groups at reproductive age. All analyses were done in SPSS, version 22, with Chi-square test, t-test, and survival analysis with p < 0.05 as significance level. RESULTS: There were minor differences in overall DMPA use during the study years. The take-out rate was equivalent to 11-12/1000 women aged 15-49 years. DMPA sales amounted to nearly 4% of all daily doses of hormonal contraceptives sold. General practitioners and physicians without a specialty were the major prescribers. The number of starters decreased by nearly 40% during the study years and was consistent across age groups. The average use duration among starters was 17.7 (95% CI 17.5-17.9) months (range 0-90). There were minor changes in the relative proportion of long-term users beyond 24 months during the study years. CONCLUSIONS: DMPA plays a minor role in the overall use of hormonal contraception in Norway, even among teenagers. The number of starters is decreasing, indicating a more restrictive attitude toward first use, especially among general practitioners.

Can oxytocin augmentation modify the risk of epidural analgesia by maternal age in cesarean sections?

INTRODUCTION: Maternal age is an established risk factor for cesarean section; epidural analgesia and oxytocin augmentation may modify this association. We investigated the effects and interactions of oxytocin augmentation, epidural analgesia and maternal age on the risk of cesarean section. MATERIAL AND METHODS: In all, 416 386 nulliparous women with spontaneous onset of labor, ≥37 weeks of gestation and singleton infants with a cephalic presentation during 2000-2011 from Norway and Denmark were included [Ten-group classification system (Robson) group 1]. In this case-control study the main exposure was maternal age; epidural analgesia, oxytocin augmentation, birthweight and time period were explanatory variables. Chi-square test and logistic regression were used to estimate associations and interactions. RESULTS: The cesarean section rate increased consistently with advancing maternal age, both overall and in strata of epidural analgesia and oxytocin augmentation. We observed strong interactions between maternal age, oxytocin augmentation and epidural analgesia for the risk of cesarean section. Women with epidural analgesia generally had a reduced adjusted odds ratio when oxytocin was used compared with when it was not used. In Norway, this applied to all maternal age groups but in Denmark only for women ≥30 years. Among women without epidural, oxytocin augmentation was associated with an increased odds ratio for cesarean section in Denmark, whereas no difference was observed in Norway. CONCLUSIONS: Oxytocin augmentation in nulliparous women with epidural analgesia is associated with a reduced risk of cesarean section in labor with spontaneous onset.

Contraceptive use in the Nordic countries.

INTRODUCTION: The aim was to compare contraceptive use in the Nordic countries and to assess compliance with recommendations from the European Medicines Agency regarding the use of combined oral contraception containing low-dose estrogen and levonorgestrel, norethisterone or norgestimate. MATERIAL AND METHODS: Data on hormonal contraceptive prescriptions and sales figures for copper intrauterine devices were obtained from national databases and manufacturers in Denmark, Finland, Iceland, Norway and Sweden in 2010-2013. RESULTS: Contraceptive use was highest in Denmark (42%) and Sweden (41%), followed by Finland (40%). Combined oral contraception was the most used method in all countries, with the highest use in Denmark (26%). The second most used method was the levonorgestrel-releasing intrauterine system, with the highest use in Finland (15%) and ≈10% in the other countries. Copper intrauterine devices (7%) and the progestin-only pill (7%) were most often used in Sweden. Combined oral contraception use decreased with increasing age and levonorgestrel-releasing intrauterine system and progestin-only pills use increased. The use of long-acting reversible methods of contraception (=levonorgestrel-releasing intrauterine system, copper intrauterine devices, and implants) increased with time and was highest in Sweden (20%) and Finland (18%). The highest use of European Medicines Agency recommended combined oral contraception was in Denmark, increasing from 13 to 50% between 2010 and 2013. In Finland, recommended combined oral contraception remained below 1%. CONCLUSIONS: Contraceptive use was highest in Denmark and Sweden, levonorgestrel-releasing intrauterine system use was highest in Finland and all long-acting methods were most common in Sweden. The use of combined oral contraception recommended by the European Medicines Agency was highest in Denmark.

High birth rates despite easy access to contraception and abortion: a cross-sectional study.

INTRODUCTION: The aim of this study was to describe and compare contraceptive use, fertility, birth, and abortion rates in the Nordic countries. MATERIAL AND METHODS: National data on births, abortions, fertility rate (1975-2013), redeemed prescriptions of hormonal contraceptives and sales figures of copper intrauterine devices (2008-2013) among women 15-49 years of age in the Nordic countries were collected and analyzed. RESULTS: Use of hormonal contraceptives and copper intrauterine devices varied between 31 and 44%. The highest use was in Denmark (39-44%) and Sweden (40-42%). Combined hormonal contraception followed by the levonorgestrel-releasing intrauterine system were the most common methods. During 1975-2013 abortion rates decreased in Denmark (from 27/1000 women to 15/1000 women aged 15-44/1000 women) and Finland (from 20 to 10/1000 women), remained stable in Norway (≈16) and Sweden (≈20) and increased in Iceland (from 6 to 15/1000 women). Birth rates remained stable around 60/1000 women aged 15-44 in all countries except for Iceland where the birth rate decreased from 95 to 65/1000 women. Abortion rates were highest in the age group 20-24 years. In the same age group, Sweden had a lower contraceptive use (51%) compared with Denmark (59%) and Norway (56%) and a higher abortion rate 33/1000 compared with Denmark (25/1000) and Norway (27/1000). CONCLUSIONS: In contrast to the declining average fertility and birth rates in Europe, rates in the Nordic countries remain high and stable despite high contraceptive use and liberal access to abortion on women's request.

Cesarean section trends in the Nordic Countries - a comparative analysis with the Robson classification.

INTRODUCTION: The cesarean rates are low but increasing in most Nordic countries. Using the Robson classification, we analyzed which obstetric groups have contributed to the changes in the cesarean rates. MATERIAL AND METHODS: Retrospective population-based registry study including all deliveries (3 398 586) between 2000 and 2011 in Denmark, Finland, Iceland, Norway and Sweden. The Robson group distribution, cesarean rate and contribution of each Robson group were analyzed nationally for four 3-year time periods. For each country, we analyzed which groups contributed to the change in the total cesarean rate. RESULTS: Between the first and the last time period studied, the total cesarean rates increased in Denmark (16.4 to 20.7%), Norway (14.4 to 16.5%) and Sweden (15.5 to 17.1%), but towards the end of our study, the cesarean rates stabilized or even decreased. The increase was explained mainly by increases in the absolute contribution from R5 (women with previous cesarean) and R2a (induced labor on nulliparous). In Finland, the cesarean rate decreased slightly (16.5 to 16.2%) mainly due to decrease among R5 and R6-R7 (breech presentation, nulliparous/multiparous). In Iceland, the cesarean rate decreased in all parturient groups (17.6 to 15.3%), most essentially among nulliparous women despite the increased induction rates. CONCLUSIONS: The increased total cesarean rates in the Nordic countries are explained by increased cesarean rates among nulliparous women, and by an increased percentage of women with previous cesarean. Meanwhile, induction rates on nulliparous increased significantly, but the impact on the total cesarean rate was unclear. The Robson classification facilitates benchmarking and targeting efforts for lowering the cesarean rates.

Mortality in myasthenia gravis: A nationwide population-based follow-up study in Denmark.

INTRODUCTION: In previous studies of myasthenia gravis (MG), increased mortality has been reported. The aim of this study was to estimate mortality in patients with acetylcholine receptor antibody-positive (AChR-Ab-seropositive) MG in a nationwide population-based, long-term follow-up study. METHODS: All AChR-Ab-seropositive MG patients, diagnosed between 1985 and 2005, were identified. Defined by age at diagnosis (≤ 50 or >50 years), patients were classified as having early- or late-onset MG. For comparison, 10 non-MG individuals from the general population were matched with each patient. All patients and controls were followed until January 1, 2009. Mortality rates and estimated mortality rate ratios (MRRs) were calculated. RESULTS: Of 702 AChR-Ab-seropositive MG patients, 302 died during follow-up. Overall mortality was higher for patients with MG (MRR = 1.41, range 1.24-1.60). In late-onset women and men, the MRRs were 1.64 (1.36-1.99) and 1.22 (1.02-1.46), respectively. Total MRR was highest during the first 5 years after diagnosis. CONCLUSIONS: MG diagnosis is still associated with increased mortality.

Navicular bone position determined by positional MRI: a reproducibility study.

OBJECTIVE: To examine intraobserver, interobserver and between-day reproducibility of positional MRI for evaluation of navicular bone height (NVH) and medial navicular position (MNP). MATERIALS AND METHODS: Positional MRI (pMRI) of the foot was performed on ten healthy participants (0.25 T G-scanner). Scanning was performed in supine and standing position, respectively. Two radiologists evaluated the images in a blinded manner. Reliability and agreement were assessed by calculation of intraclass correlation coefficient (ICC) and 95 % limits of agreement as a percentage of the mean (LOA%). RESULTS: Intraobserver and interobserver reliability was "substantial" in both supine and standing position (ICC 0.86-0.98) and showed good agreement (LOA% 4.9-14.7 %). Between-day reliability of navicular height and medial navicular position in standing position remained substantial (ICC 0.85-0.92) with adequate agreement (LOA% 8.3-19.8 %). In supine position between-day reliability was "moderate" for NVH (ICC 0.72) and "slight" for MNP (ICC 0.39). Agreement remained adequate between-days for MNP in supine position (LOA% 17.7 %), but it was less than adequate for NVH in supine position (LOA% 24.2 %). CONCLUSION: Navicular height and medial navicular position can be measured by pMRI in a very reproducible manner within and between observers. Increased measurement variation is observed between-days in supine position, which may be due to small positional differences or other unknown biomechanical factors.

Single-Electron Detection and Spectroscopy via Relativistic Cyclotron Radiation.

It has been understood since 1897 that accelerating charges must emit electromagnetic radiation. Although first derived in 1904, cyclotron radiation from a single electron orbiting in a magnetic field has never been observed directly. We demonstrate single-electron detection in a novel radio-frequency spectrometer. The relativistic shift in the cyclotron frequency permits a precise electron energy measurement. Precise beta electron spectroscopy from gaseous radiation sources is a key technique in modern efforts to measure the neutrino mass via the tritium decay end point, and this work demonstrates a fundamentally new approach to precision beta spectroscopy for future neutrino mass experiments.

Neonatal outcome of singleton term breech deliveries in Norway from 1991 to 2011.

INTRODUCTION: The objective of this study was to examine the association between planned mode of delivery and neonatal outcomes in breech deliveries. MATERIAL AND METHODS: In this retrospective cohort study we studied singleton term breech deliveries in Norway from 1991 to 2011 (n = 30 861) using the Medical Birth Registry of Norway. We compared planned vaginal delivery with planned cesarean delivery across two time periods: from 1 January 1991 to 31 October 2000 (first period) and from 1 November 2000 to 31 December 2011 (second period). Intrapartum and neonatal deaths were validated against source data in medical records, autopsy reports, and other relevant documents. The main outcome measures were intrapartum and neonatal mortality within the first 28 days of life, 5-min Apgar-scores <7 and <4, neonatal intensive care unit stays ≥4 days, respiratory morbidity, and intracranial bleeding disorders. RESULTS: Rate of planned cesarean delivery increased from 34.4 to 51.3% over the period. Simultaneously, early neonatal mortality rate (0-6 days) declined (from 0.10% to 0.04%, p = 0.04). During the second period, 30.7% of term breech presentations were delivered vaginally. Eight deaths in the planned vaginal vs. four in the planned cesarean groups were observed (OR 2.11 95% CI 0.64-7.01). Neonatal morbidity outcomes were significantly worse in planned vaginal deliveries compared with planned cesarean deliveries in both periods. CONCLUSION: Overall intrapartum and neonatal mortality decreased during the entire period. Higher mortality in planned vaginal delivery relative to planned cesarean delivery in the second period was not statistically significant. However, neonatal morbidity was significantly higher in planned vaginal than planned cesarean deliveries in both periods. This warrants continuous surveillance of breech deliveries.

Demonstration of multilayer reflective optics at photon energies above 0.6 MeV.

Focusing optics operating in the soft gamma-ray photon energy range can advance a range of scientific and technological applications that benefit from the large improvements in sensitivity and resolution that true imaging provides. An enabling technology to this end is multilayer coatings. We show that very short period multilayer coatings deposited on super-polished substrates operate efficiently above 0.6 MeV. These experiments demonstrate that Bragg scattering theory established for multilayer applications as low as 1 eV continues to work well into the gamma-ray band.

The increased risk of venous thromboembolism by advancing age cannot be attributed to the higher incidence of cancer in the elderly: the Tromsø study.

UNLABELLED: Whether the high incidence of venous thromboembolism (VTE) in the elderly can be attributed to cancer is not well studied. We assessed the impact of cancer on risk of VTE in young, middle-aged and elderly. 26,094 subjects without a history of cancer or VTE were recruited from the Tromsø study. Incident cancer (n = 2,290) and VTE (n = 531) were recorded from baseline (1994-1995) through December 31st, 2009. Cox regression with cancer as time-varying exposure was used to calculate hazard ratios with 95 % confidence intervals (CI). Overt cancer was associated with a fivefold (95 %CI 4.3, 6.7) increased risk of VTE, with an age-dependent gradient from 26-fold (95 %CI 12.1, 56.5) increased in the young, ninefold (95 % CI 6.6, 12.7) increased in the middle-aged, and threefold (95 % CI 2.5, 4.5) increased risk in the elderly. The population attributable risks were 14, 27 and 18 %, respectively. CONCLUSION: The relative risk of VTE by cancer were higher in young compared to elderly subjects, but the proportion of VTEs in the population due to cancer did not differ much across age groups. Our findings indicate that the increased risk of VTE by advancing age cannot be attributed to higher incidence of cancer in the elderly.

Incidence and Characteristics of the Hyperosmolar Hyperglycemic State: A Danish Cohort Study.

OBJECTIVE: The hyperosmolar hyperglycemic state (HHS) is a rare and life-threatening complication of diabetes. We aimed to estimate the incidence of HHS and describe the clinical and biomarker profiles of patients with HHS, including subgroups with acidosis and acute kidney injury. RESEARCH DESIGN AND METHODS: This nationwide, descriptive cohort study used Danish registry data during years 2016-2018 to identify acutely admitted patients fulfilling the hyperglycemia and hyperosmolarity criteria of HHS (glucose ≥33 mmol/L and osmolarity [2 × sodium + glucose] ≥320 mmol/L). RESULTS: We identified 634 patients (median age, 69 years (first quartile; third quartile: 58; 79) who met the criteria of HHS among 4.80 million inhabitants aged ≥18 years. The incidence rates were 16.5 and 3.9 per 10,000 person-years among people with known type 1 (n = 24,196) and type 2 (n = 251,357) diabetes, respectively. Thirty-two percent of patients with HHS were not previously diagnosed with diabetes. Patients were categorized as pure HHS (n = 394) and combined HHS and diabetic ketoacidosis (HHS-DKA; n = 240). The in-hospital mortality rate for pure HHS was 17% and 9% for HHS-DKA. CONCLUSIONS: The incidence of HHS was higher among patients with type 1 diabetes compared with type 2 diabetes. HHS is a spectrum of hyperglycemic crises and can be divided in pure HHS and HHS-DKA. In one-third of patients, HHS was the debut of their diabetes diagnosis.