Incidence of myeloproliferative neoplasms - trends by subgroup and age in a population-based study in Sweden.

BACKGROUND: The reported incidence of Philadelphia-negative myeloproliferative neoplasms (MPNs) differs substantially between previous reports, likely due to true regional differences in incidence and/or variations in the quality and coverage of the cancer registers. OBJECTIVE: We therefore assessed MPN incidence in Sweden during recent years using prospectively collected information captured in Swedish health registers. METHODS: Patients with MPNs were identified through the Swedish Cancer Register and Swedish Blood Cancer Register between 2000 and 2014. Information on the Swedish population was obtained from the Human Mortality Database. Crude and age-standardized incidence rates of MPNs with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 6281 MPN cases were reported to the Swedish Cancer Register and Swedish Blood Cancer Register during 2000-2014. The age-standardized, to the Swedish population in 2000, incidence for all MPNs was 4.45 (95% confidence interval [CI] 4.34-4.56)/100 000 person-years. The age-standardized incidence for polycythemia vera was 1.48 (1.42-1.54), for essential thrombocythemia 1.60 (1.53-1.66) and for primary myelofibrosis 0.52 (0.48-0.56)/100 000 person-years, respectively. The incidence rate of MPNs was substantially higher in the older compared to the younger age groups. The incidence increased during the study period, likely to do better reporting and increasing age of the general population. CONCLUSION: The reported MPN incidences in our study, which were in the higher interval of previously published studies, are likely more accurate compared to previous reports due to the population-based setting and high level of coverage in the Swedish Cancer and Blood Cancer Registers.

Prevalence of myeloma precursor state monoclonal gammopathy of undetermined significance in 12372 individuals 10-49 years old: a population-based study from the National Health and Nutrition Examination Survey.

We studied the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in younger individuals, age 10-49 years, using samples from the National Health and Nutritional Examination Survey (NHANES) III. NHANES prevalence rates were standardized to the 2000 US total population. Among 12 372 individuals (4073 blacks, 4146 Mexican-Americans, 3595 whites, and 558 others), MGUS was identified in 63 persons (0.34%, 95% CI 0.23-0.50). The prevalence of MGUS was significantly higher in blacks (0.88%, 95% CI 0.62-1.26) compared with whites (0.22%, 95% CI 0.11-0.45), P=0.001. The prevalence of MGUS in Mexican-Americans was at an intermediate level (0.41%, 95% CI 0.23-0.73). The disparity in prevalence of MGUS between blacks and whites was most striking in the 40-49 age-group; 3.26% (95% CI 2.04-5.18) versus 0.53% (95% CI 0.20-1.37), P=0.0013. There was a trend to earlier age of onset of MGUS in blacks compared with whites. MGUS was seen in only two persons in the 10-19 age-group (both Mexican-American), and in three persons in the 20-29-year age-group (all of whom were black). In persons less than 50 years of age, MGUS is significantly more prevalent, with up to 10 years earlier age of onset, in blacks compared with whites.

Peripheral facial palsy: Speech, communication and oral motor function.

OBJECTIVES: The aim of the present study was to examine the effect of acquired unilateral peripheral facial palsy on speech, communication and oral functions and to study the relationship between the degree of facial palsy and articulation, saliva control, eating ability and lip force. MATERIALS AND METHODS: In this descriptive study, 27 patients (15 men and 12 women, mean age 48years) with unilateral peripheral facial palsy were included if they were graded under 70 on the Sunnybrook Facial Grading System. The assessment was carried out in connection with customary visits to the ENT Clinic and comprised lip force, articulation and intelligibility, together with perceived ability to communicate and ability to eat and control saliva conducted through self-response questionnaires. RESULTS: The patients with unilateral facial palsy had significantly lower lip force, poorer articulation and ability to eat and control saliva compared with reference data in healthy populations. The degree of facial palsy correlated significantly with lip force but not with articulation, intelligibility, perceived communication ability or reported ability to eat and control saliva. CONCLUSION: Acquired peripheral facial palsy may affect communication and the ability to eat and control saliva. Physicians should be aware that there is no direct correlation between the degree of facial palsy and the possible effect on communication, eating ability and saliva control. Physicians are therefore recommended to ask specific questions relating to problems with these functions during customary medical visits and offer possible intervention by a speech-language pathologist or a physiotherapist.

Synkinesis in Bell's palsy in a randomised controlled trial.

OBJECTIVES: To study the development of synkinesis in Bell's palsy. Frequency, severity, gender aspects and predictors were analysed. DESIGN: Data from the randomised controlled Scandinavian Bell's palsy trial including 829 patients. MAIN OUTCOME MEASURES: Frequency and severity of synkinesis at 12 months were the main outcome measures. Mean Sunnybrook synkinesis scores, voluntary movement scores and composite scores between 6 and 12 months were compared. RESULTS: In 743 patients with a 12-month follow-up, synkinesis frequency was 21.3%. There was no gender difference. Synkinesis was moderate to severe in 6.6% of patients. Those with synkinesis at 6 months had a synkinesis score of 4.1 (±2.8 sd), which increased to 4.7 (±3.2) (P = 0.047) at 12 months (n = 93). Sunnybrook composite score at 1 month was the best predictor for synkinesis development with receiver operating characteristics and area under the curve (AUC) 0.87. Risk for synkinesis increased with a lower Sunnybrook composite score. Furthermore, at 1 month, symmetry of voluntary movement had higher predictive value for synkinesis than resting symmetry with AUC 0.87 and 0.77, respectively. Gentle eye closure and open-mouth smile were the only independent significant predictive items (AUC 0.86). CONCLUSIONS: Moderate-to-severe synkinesis was present in 6.6% of patients. The mean synkinesis score increased between 6 and 12 months, and outcome should therefore be evaluated after at least 12 months. Sunnybrook composite score and symmetry of voluntary movement at 1 month were good predictors for synkinesis.

Elevated risk of venous but not arterial thrombosis in Waldenström macroglobulinemia/lymphoplasmacytic lymphoma.

BACKGROUND: Many malignancies, including multiple myeloma and its precursor, monoclonal gammopathy of unknown significant, are associated with an elevated risk of thromboembolism. There is limited information on the risk of thrombosis in patients with Waldenström macroglobulinemia (WM) and lymphoplasmacytic lymphoma (LPL). OBJECTIVES: To assess the risk of venous and arterial thrombosis in WM/LPL patients in a large population-based cohort study in Sweden. PATIENTS/METHODS: A total of 2190 patients with WM/LPL and 8086 matched controls were identified through Swedish registers between 1987 and 2005. Information on occurrence of venous and arterial thrombosis after the diagnosis of WM/LPL was obtained through the centralized Swedish Patient Register, with follow-up to 2006. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Patients with WM/LPL had a significantly increased risk of venous thrombosis and the highest risk was observed during the first year following diagnosis (HR = 4.0, 95% CI 2.5-6.4). The risk was significantly elevated 5 (HR = 2.3, 95% CI 1.7-3.0) and 10 years after diagnosis (HR = 2.0, 95% CI 1.6-2.5). There was no increased risk of arterial thrombosis during any period of follow-up time (10-year HR = 1.0, 95% CI 0.9-1.1). CONCLUSIONS: Venous thrombosis is a significant cause of morbidity in patients with WM/LPL. The potential role of thromboprophylaxis in WM/LPL, especially during the first year after diagnosis and in patients treated with thrombogenic agents, needs to be assessed to further improve outcome in WM/LPL patients.

Limited evidence for the use of imaging to detect prostate cancer: a systematic review.

OBJECTIVE: To assess the diagnostic accuracy of imaging technologies for detecting prostate cancer in patients with elevated PSA-values or suspected findings on clinical examination. METHODS: The databases Medline, EMBASE, Cochrane, CRD HTA/DARE/NHS EED and EconLit were searched until June 2013. Pre-determined inclusion criteria were used to select full text articles. Risk of bias in individual studies was rated according to QUADAS or AMSTAR. Abstracts and full text articles were assessed independently by two reviewers. The performance of diagnostic imaging was compared with systematic biopsies (reference standard) and sensitivity and specificity were calculated. RESULTS: The literature search yielded 5141 abstracts, which were reviewed by two independent reviewers. Of these 4852 were excluded since they did not meet the inclusion criteria. 288 articles were reviewed in full text for quality assessment. Six studies, three using MRI and three using transrectal ultrasound were included. All were rated as high risk of bias. Relevant studies on PET/CT were not identified. CONCLUSION: Despite clinical use, there is insufficient evidence regarding the accuracy of imaging technologies for detecting cancer in patients with suspected prostate cancer using TRUS guided systematic biopsies as reference standard.

Infants under the age of six months with acute mastoiditis. A descriptive study of 15 years in Sweden.

OBJECTIVE: To investigate the occurrence, clinical signs and outcome of acute mastoiditis in infants under the age of 6 months in Sweden between the years 1993-2007. METHODS: All ENT departments in Sweden reported children 0-5 months treated for acute mastoiditis 1993-2007 and all records were reviewed. The clinical course and various characteristics were recorded. RESULTS: Seventeen young infants with acute mastoiditis were identified. Three patients had suffered acute otitis media earlier, otherwise the children were previously healthy. Preceding the episode of acute mastoiditis, the children had an upper respiratory tract infection or fever for seven days in mean (median three days) and the mean number of days with ear-symptoms was three days (median two days). Three patients were treated with antibiotics prior to admittance. Almost all children presented with clear retroauricular signs with protruding ear and redness behind the ear. The children were hospitalised for six days (mean and median). Eight patients (47%) suffered from a subperiosteal abscess. All but one patient underwent surgery: myringotomy (13); incision or punction of the mastoid (5); mastoidectomy (3). Streptococcus pneumoniae was the most frequent bacterium identified in cultures. No intracranial complications or other severe complications were found. CONCLUSION: Acute mastoiditis is extremely rare in infants under the age of 6 months. The patients in this study did not have any predisposing diseases. An upper respiratory tract infection had preceded the episode of acute mastoiditis for some time in the majority of cases, but the time from first ear symptoms to hospitalization was very short. Acute mastoiditis is a potentially life-threatening disease, but the timely administration of intravenous antibiotics and surgical intervention prevented the occurrence of severe complications in these young infants.

National assessment of validity of coding of acute mastoiditis: a standardised reassessment of 1966 records.

OBJECTIVES: To investigate the internal validity of the diagnosis code used at discharge after treatment of acute mastoiditis. DESIGN: Retrospective national re-evaluation study of patient records 1993-2007 and make comparison with the original ICD codes. SETTING: All ENT departments at university hospitals and one large county hospital department in Sweden. PARTICIPANTS: A total of 1966 records were reviewed for patients with ICD codes for in-patient treatment of acute (529), chronic (44) and unspecified mastoiditis (21) and acute otitis media (1372). MAIN OUTCOME MEASURES: ICD codes were reviewed by the authors with a defined protocol for the clinical diagnosis of acute mastoiditis. Those not satisfying the diagnosis were given an alternative diagnosis. RESULTS: Of 529 records with ICD coding for acute mastoiditis, 397 (75%) were found to meet the definition of acute mastoiditis used in this study, while 18% were not diagnosed as having any type of mastoiditis after review. Review of the in-patients treated for acute media otitis identified an additional 60 cases fulfilling the definition of acute mastoiditis. Overdiagnosis was common, and many patients with a diagnostic code indicating acute mastoiditis had been treated for external otitis or otorrhoea with transmyringeal drainage. CONCLUSIONS: The internal validity of the diagnosis acute mastoiditis is dependent on the use of standardised, well-defined criteria. Reliability of diagnosis is fundamental for the comparison of results from different studies. Inadequate reliability in the diagnosis of acute mastoiditis also affects calculations of incidence rates and statistical power and may also affect the conclusions drawn from the results.

Healing of laser-induced tympanic membrane perforations in rats: no contribution of granulocyte colony-stimulating factor or Gelfoam.

OBJECTIVES: To study whether granulocyte colony-stimulating factor together with Gelfoam (absorbable gelatin sponge, USP) could enhance the healing of freshly perforated tympanic membranes. The frequency and occurrence of different immunocompetent cells and collagen types was noted. METHODS: Laser perforations were made in the tympanic membrane of rats that were sacrificed at different time intervals post-myringotomy: Day 1, 3, 6, and 12. Tympanic membrane specimens were embedded and sections were stained with hematoxylin/eosin and an immunohistochemical technique was used, with antibodies against macrophages, B-cells, T-cells, and type I-IV collagens. Semi-quantification was performed after counting positive cells, mean values were calculated and analyzed statistically. RESULTS: All perforations, except one, had closed by Day 12 and no difference was observed between experimental and control ears at the other time points. Gelfoam was still present in a high amount at Day 12. The sections were initially stained positive for type I and II collagen, but after Day 6, the regenerating tissue stained positive for mainly type III and IV collagens. Results showed that the recruitment of macrophages, B-cells, and T-cells could not be mapped with a statistical significance. CONCLUSIONS: This study showed that at 6-12 days post-laser myringotomy, type III and IV collagen has replaced the collagen type II that normally constitutes the healthy tympanic membrane. There is a concern for excessive scarring involving adjacent structures. It was also seen that the combination of Gelfoam and granulocyte colony-stimulating factor or saline did not affect the healing times in perforated tympanic membranes. No significant results regarding the inflammatory cell recruitment could be obtained on the studied time points or between experimental and control ears, except for in the Gelfoam matrix.

Alloreactivity but failure to reject human islet transplants by humanized Balb/c/Rag2gc mice.

A human islet transplant can cure patients with type 1 diabetes. A drawback of islet transplantation is the life-long immunosuppressive medication, often associated with severe side effects. Moreover, in spite of the immunosuppressive therapy, islets are lost in the majority of transplanted patients over time. An improved small animal model for studies on human islet allograft rejection mechanisms and the development of new measures for its prevention is clearly warranted. Here, we evaluated the potential of Balb/cRag2(-/-)gammac(-/-) mice carrying a human-like immune system (so-called humanized mice) as a tool for studies on the rejection of transplanted human islets. Human T cells from Balb/cRag2(-/-)gammac(-/-) mice, which as neonates had been transplanted with CD34(+) human cord blood haematopoietic stem cells (HIS mice), proliferated in response to allogeneic human dendritic cells, but failed to reject a human islet allograft transplanted to the renal subcapsular space as assessed by immunohistochemistry and analysis of human serum C-peptide levels. Histological analysis revealed that few if any T cells had migrated to the grafted tissue. These observations question the usefulness of the HIS mouse model for studies on human islet allograft rejection mechanisms and highlight the need for further improvements.

The menopause triggers hearing decline in healthy women.

BACKGROUND: Epidemiological studies have shown that women have better high-frequency thresholds than men in virtually all age groups, and that age-related hearing decline starts after 30 in men but not until after the age of 50 in women. This coincides with the menopausal transition in most women, thus leading us to hypothesize that the menopause triggers auditory deterioration, possibly due to reduced levels of endogenous estrogens, which are known to have protective effects on the auditory system. METHODS: 104 women with a mean age 51.2 at baseline, were tested with pure tone audiometry twice with an average interval of 7.5 years. The age at the final menstrual period (FMP) was reported by all women. Hearing decline at individual frequencies was calculated. RESULTS: Women with a FMP 0-4 years ago, had a rate of high frequency hearing decline of 0.9-1.5dB/year in the left ear, those with 5-7 years since the FMP had a corresponding rate of 1.1-1.5dB/year in the right ear, and 8-13 years after the FMP the decline was more subtle, 0.7-1.1dB/year in both ears. CONCLUSION: The menopause appears to act as a trigger of a relatively rapid age-related hearing decline in healthy women, starting in the left ear.

The target cell response to cytokines governs the autoreactive T cell repertoire in the pancreas of NOD mice.

AIMS/HYPOTHESIS: The pancreatic beta cell response to cytokines is crucial for the development of type 1 diabetes in the NOD mouse. For example, beta cell production of suppressor of cytokine signalling-1 (SOCS-1) protects against diabetes. This finding and other recent studies indicated that cytokine-stressed beta cells might contribute to disease progression by affecting the pancreatic lymphocyte infiltrate. The aim of this study was to provide insight into how the beta cell influences the pancreas-infiltrating T cell repertoire. METHODS: Lymphocytes isolated from Socs1-transgenic (tg) and non-tg NOD mice were analysed by flow cytometry. mRNA and protein levels in pancreatic islets were measured by real-time PCR and immunofluorescence analysis, respectively. RESULTS: The percentages of regulatory T cells, total counts and ratios between infiltrating CD8+ and CD4+ T cells, and the expression of killer cell lectin-like receptor subfamily K, member 1 (NKG2D) on CD8+ T cells did not differ in pancreases from prediabetic Socs1-tg and non-tg NOD mice. However, a striking difference in the percentages of CD8+ T cells specific for glucose 6-phosphatase catalytic subunit-related protein 206-214 was found, showing that SOCS-1 prevents the accumulation of high percentages of self-reactive CD8+ T cells in the pancreas. It was also found that protection from diabetes in Socs1-tg NOD mice correlated with a reduced expression of Cxcl10 mRNA in IFN-gamma treated islets. CONCLUSIONS/INTERPRETATION: This study highlights an important role for the beta cell in the local regulation of the diabetogenic process. By responding to the pro-inflammatory pancreas milieu it strongly influences the islet-reactive T cell repertoire in the pancreas.

Psychosocial work environment and lifestyle as related to lipid profiles in perimenopausal women.

OBJECTIVE: The aim of the study was to characterize lipid profiles of perimenopausal women and to relate these to the psychosocial work environment and lifestyle using a longitudinal design. METHODS: A population-based sample of 107 women, aged 47-53 years, participated in a baseline study and in a follow-up 2 years later. Psychosocial work stress was measured using the Job Content Questionnaire. The women also completed a health questionnaire and participated in a psychological interview. Fasting blood samples were analyzed for concentrations of total cholesterol, high and low density lipoprotein (HDL, LDL) cholesterol and triglycerides. RESULTS: Multiple regression analyses showed that work control was a significant predictor of higher HDL cholesterol (p<0.05), lower LDL cholesterol/HDL cholesterol ratio (p<0.01) and lower total cholesterol/HDL cholesterol ratio (p<0.01). Job strain predicted a higher LDL cholesterol/HDL cholesterol ratio (p<0.01) and higher total cholesterol/HDL cholesterol ratio (p<0.05). Lifestyle variables smoking, body mass index and waist/hip ratio predicted an unfavorable lipid profile, whereas alcohol consumption predicted a favorable lipid profile. Age but not menopausal status was associated with lipid levels at baseline and on follow-up. Use of hormone replacement therapy was a significant predictor of lower cholesterol levels in the multivariate analyses. CONCLUSIONS: Our results demonstrated a significant association between the psychosocial work environment and women's cardiovascular health at menopause. Job strain was a significant contributor to an atherogenic lipid profile, whereas work control predicted a favorable profile. Hence, the argument is now compelling that psychosocial factors should be included in the risk profiles for cardiovascular disease in women.

Estrogen and hearing: a summary of recent investigations.

Is the female sex steroid estrogen the key to preserved hearing in the aging human? This question remains unanswered, but hearing loss is more profound in elderly males than females. There are also well-known sex differences in the auditory brainstem response (ABR), i.e. women have shorter latencies than men. Moreover, menopausal women who are administered hormone replacement therapy have slightly better hearing than those who are not, and women with Turner's syndrome (45,X), who are biologically estrogen-deficient, show longer ABR latencies and early presbyacusis. These findings are also supported by animal experiments. When boosted with estrogen or testosterone the non-reproductive female midshipman fish alters its inner ear auditory mechanism so that it can hear the male's hum-like call. If estrogen receptor beta is knocked out in mice, severe progressive hearing loss occurs, leading to early deafness. In apparent contradiction to these findings, there have been case reports suggesting that hormone replacement therapy and oral contraceptive use can lead to hearing loss, but of another type, namely acute sudden deafness. Such contradictory aspects of the action of estrogen are commonly found and may spring from the fact that there are two estrogen receptors, alpha and beta, both of which are present in the inner ear of mice, rats and humans. Knowing how sex steroids can alter hearing ability may give important clues as to how estrogen can preserve hearing in humans. In this review we present a summary of current knowledge about hearing and estrogen.

Effect of estrogen and antiestrogens on the estrogen receptor content in the cochlea of ovariectomized rats.

Older women in the normal population tend to develop less severe hearing loss as compared to males in the same age. In Turner syndrome (45,X), estrogen deficiency is one of the predominant problems. Ear and hearing problems are common among these patients. Does estrogen have an impact on the hearing organ? Twenty-four rats were ovariectomized and treated with vehicle (controls), estradiol or selective estrogen receptor modulators such as tamoxifen and ICI182780, in order to study the effects on the estrogen receptor levels and distribution in the inner ear. The cochleas were stained immunohistochemically using antibodies against estrogen receptor alpha and beta. No major difference in estrogen receptor content in the cochleas was observed among groups. There was however a potential down regulation of estrogen receptor alpha in the marginal cells of stria vascularis in the rats that were substituted with ICI182780 (pure antiestrogen) as compared to those given estradiol or tamoxifen. When investigating the tissues with light microscopy no change in inner ear anatomy could be observed.

Ear and hearing problems in Turner's syndrome.

OBJECTIVES: To report hearing results in Swedish women with Turner's syndrome (TS), describe the recommendations of the Otologic Section of the Swedish Turner Academy for handling these patients and discuss the effect of estrogen on hearing in animals. MATERIAL AND METHODS: Audiometric and karyotype tests were performed in 325 Swedish women with TS. A questionnaire was completed by 143 females with TS. Immunohistochemical staining of inner ear specimens was undertaken using antibodies against estrogen receptors in both human fetuses with TS and middle-aged women. Temporal bones obtained from various animal species were also studied immunohistochemically. RESULTS: A total of 61% of the women had suffered from otitis media. A senorineural dip in hearing could be observed as early as the age of 6 years, progressed over time and was related to karyotype. The results of the questionnaire revealed that hearing impairment was rated as the fourth most serious problem associated with TS. The immunohistochemical study confirmed that estrogen receptors are present in the inner ear of humans. The animal experiments showed that estrogen receptors were present at almost equal amounts in rats, mice, TS mice, beta knockout mice and ovariectomized rats and at the same localization as in the human inner ear. CONCLUSIONS: Both the senorineural dip in hearing and the karyotype can be used to predict the future course of hearing problems in TS patients. Estrogen may have an effect on hearing loss in TS patients but this phenomenon requires further investigation.