Practical guidance for assessing and reporting lymphovascular space invasion (LVSI) in endometrial carcinoma.

Lymphovascular space invasion (LVSI) is an important prognostic parameter in endometrial carcinoma (EC) and has gained increasing interest in recent years due to an expanding body of evidence of its independent prognostic value, especially when the presence of LVSI is quantified. A key strength of LVSI as a prognostic factor is that it can be detected on routine microscopic examination, without ancillary tests, and thus can be used in low-resource settings. A weakness, however, is the lack of uniformly applied criteria for assessment and quantification of LVSI, resulting in interobserver variation in diagnosis. This is confounded by artefacts and other morphological features that may mimic LVSI (commonly referred to as pseudo-LVSI). Despite these issues, multiple studies have shown that LVSI is strongly associated with lymph node (LN) metastasis and is an independent risk factor for LN recurrence and distant metastasis. Consequently, the presence of substantial/extensive LVSI has become an important consideration in formulating adjuvant treatment recommendations in patients with EC, and this has been incorporated in the recent International Federation of Gynecology and Obstetrics (FIGO) 2023 staging system. Herein, we review the current literature on LVSI in EC and discuss its role as a prognostic marker, the reproducibility of LVSI assessment and distinction between LVSI and its mimics. We provide illustrations of key diagnostic features and discuss the two-tiered (none/focal versus substantial) system of LVSI classification. This work is intended to provide guidance to practising pathologists and unify the approach towards LVSI assessment in EC.

[Social pediatric care situation and needs during the COVID-19 pandemic from 2020 to 2022. What is needed now?] / Sozialpädiatrische Versorgungssituation und -bedarfe in Zeiten der COVID-19-Pandemie 2020 bis 2022. Was wird jetzt gebraucht?

BACKGROUND: Children and adolescents with social pediatric care needs represent a group with special challenges. The aim of this qualitative study was to describe social pediatric care during the pandemic from the perspective of experts. From this, conclusions were to be drawn for any social pediatric care needs that may have arisen. METHODS: Between May and November 2022, 25 experts from the field of social pediatrics were interviewed using guided interviews on the following topics: deviations in care, utilization behavior of families, individual burdens and resources, and sustainable needs. The interviews were analyzed by two research assistants. RESULTS: Overall, the social pediatric care offer was temporarily clearly limited. While families who were already well connected before the pandemic could be adequately cared for with the help of telephone/video contacts, an unreported number of at-risk groups, were described, for example, those with low competence to act, who did not make use of services or did so with delays. It was observed that there was a need for care for newly developed mental disorders and regression in therapy due to limited opportunities for support, as well as a need to catch up on missed opportunities for early support in the case of developmental disorders. DISCUSSION: To meet the needs that have arisen, underserved families should be identified and cared for promptly, taking individual characteristics into account. To this end, for example, more outreach services should be established that reach affected families unbureaucratically.

Prognostic relevance of the molecular classification in high-grade endometrial cancer for patients staged by lymphadenectomy and without adjuvant treatment.

INTRODUCTION: The clinical role of the molecular endometrial cancer (EC) classification has not been fully explored in patients staged with lymphadenectomy or without adjuvant treatment, conditions that could potentially moderate the prognostic value of the classification. We aimed to evaluate the clinical outcome of the molecular subgroups in patients with high-grade EC staged by lymphadenectomy and those without adjuvant treatment. METHODS: DNA-sequencing for the detection of pathogenic POLE-exonuclease domain mutations and immunohistochemistry for mismatch repair (MMR) proteins and p53 expression were performed on 412 high-grade EC from the Danish Gynaecological Cancer Database (2005-2012) to classify them as POLE-ultramutated (POLEmut), MMR-deficient (MMRd), p53-mutant (p53abn), or no specific molecular profile (NSMP). Patients with stage IV or residual disease after surgery were excluded. Kaplan-Meier method, log-rank test and Cox proportional hazard models were used for analysis. RESULTS: Molecular analysis was successful in 367 EC; 251 patients had undergone lymphadenectomy. Five-year recurrence rates in this subgroup of patients was 36.7% for women with p53abn EC, 0.0% for POLEmut EC, 13.4% for MMRd EC and 42.9% for NSMP EC (p < 0.001). Similar results were observed among stage IA-IB patients. Among patients without adjuvant treatment (n = 264), none with POLEmut EC (n = 26) had a recurrence. CONCLUSION: The molecular EC classification has strong prognostic value, independent of clinicopathological factors, also among high-grade EC patients staged by lymphadenectomy and those without adjuvant treatment. The unfavourable prognosis of early-stage p53abn EC is not due to undetected lymph node metastasis, and the indolent behaviour of POLEmut EC is independent of adjuvant treatment.

Substantial Lymphovascular Space Invasion Is an Adverse Prognostic Factor in High-Risk Endometrial Cancer.

Approximately 15% of patients with endometrial cancer present with high-risk disease (HREC). Moreover, assessing the extent of lymphovascular space invasion (LVSI) may provide prognostic insight among patients with HREC. The aim of this study was to determine whether the extent of LVSI can serve as a prognostic factor in HREC. All cases of ESMO-ESGO-ESTRO 2016 classified HREC in the Danish Gynecological Cancer Database (DGCD) diagnosed from 2005 to 2012 were reviewed for the presence and extent of LVSI (categorized using a 3-tiered definition). We used the Kaplan-Meier analysis to calculate actuarial survival rates, both adjusted and unadjusted Cox regression analyses were used to calculate the proportional hazard ratio (HR). A total of 376 patients were included in our analysis. Among 305 patients with stage I/II HREC, 8.2% and 6.2% had focal or substantial LVSI, respectively, compared with 12.7% and 38.0% of 71 patients with stage III/IV HREC, respectively. Moreover, the estimated 5-yr recurrence-free survival rate was significantly lower among patients with substantial LVSI compared with patients with no LVSI for both stage I/II (HR: 2.8; P=0.011) and stage III/IV (HR: 2.9; P=0.003) patients. Similarly, overall survival was significantly lower among patients with substantial LVSI for both stage I/II (HR: 3.1; P<0.001) and stage III/IV (HR: 3.2; P=0.020) patients. In patients with HREC, substantial LVSI is an independent adverse prognostic factor for lymph node and distant metastases, leading to reduced survival. Thus, the extent of LVSI should be incorporated into routine pathology reports in order to guide the appropriate choice of adjuvant treatment.

Defining Substantial Lymphovascular Space Invasion in Endometrial Cancer.

Lymphovascular space invasion (LVSI) occurs in a minority of endometrial cancer (EC) cases, and the extent of LVSI is an important risk factor for recurrence and/or metastases. Our aim was to improve the reproducibility of measuring clinically meaningful LVSI by performing a quantitative analysis of the correlation between LVSI and the risk of pelvic lymph node recurrence in EC. EC samples from PORTEC-1 and PORTEC-2 trials were retrieved and used to collect quantitative data, including the number of LVSI-positive vessels per H&E-stained slide. Using a predefined threshold for clinical relevance, the risk of pelvic lymph node recurrence risk was calculated (Kaplan-Meier method, with Cox regression) using a stepwise adjustment for the number of LVSI-positive vessels. This analysis was then repeated in the Danish Gynecological Cancer Database (DGCD) cohort. Among patients in PORTEC-1 and PORTEC-2 trials who did not receive external beam radiotherapy, the 5-yr pelvic lymph node recurrence risk was 3.3%, 6.7% (P=0.51), and 26.3% (P<0.001), respectively when 0, 1 to 3, or ≥4 vessels had LVSI involvement; similar results were obtained for the DGCD cohort. Furthermore, both the average number of tumor cells in the largest embolus and the number of LVSI-positive H&E slides differed significantly between focal LVSI and substantial LVSI. On the basis of these results, we propose a numeric threshold (≥4 LVSI-involved vessels in at least one H&E slide) for defining clinically relevant LVSI in EC, thereby adding supportive data to the semiquantitative approach. This will help guide gynecologic pathologists to differentiate between focal and substantial LVSI, especially in borderline cases.

Reproducibility of lymphovascular space invasion (LVSI) assessment in endometrial cancer.

AIMS: Lymphovascular space invasion (LVSI) in endometrial cancer (EC) is an important prognostic variable impacting on a patient's individual recurrence risk and adjuvant treatment recommendations. Recent work has shown that grading the extent of LVSI further improves its prognostic strength in patients with stage I endometrioid EC. Despite this, there is little information on the reproducibility of LVSI assessment in EC. Therefore, we designed a study to evaluate interobserver agreement in discriminating true LVSI from LVSI mimics (Phase I) and reproducibility of grading extent of LVSI (Phase II). METHODS AND RESULTS: Scanned haematoxylin and eosin (H&E) slides of endometrioid EC (EEC) with a predefined possible LVSI focus were hosted on a website and assessed by a panel of six European gynaecological pathologists. In Phase I, 48 H&E slides were included for LVSI assessment and in Phase II, 42 H&E slides for LVSI grading. Each observer was instructed to apply the criteria for LVSI used in daily practice. The degree of agreement was measured using the two-way absolute agreement average-measures intraclass correlation coefficient (ICC). Reproducibility of LVSI assessment (ICC = 0.64, P < 0.001) and LVSI grading (ICC = 0.62, P < 0.001) in EEC was substantial among the observers. CONCLUSIONS: Given the good reproducibility of LVSI, this study further supports the important role of LVSI in decision algorithms for adjuvant treatment.

Tenosynovitis caused by Mycobacterium malmoense in two kidney transplant recipients and review of the literature.

We report two unrelated cases of tenosynovitis caused by Mycobacterium malmoense in kidney transplant recipients. Both patients received immunosuppression and were referred to our tertiary hospital because of persisting complaints lasting >6 months not responding to corticosteroids or surgery. The mycobacterial cultures were positive for the slow-growing M. malmoense after several weeks of incubation. The patient in Case 1 was treated with a combination of surgical debridement and antibiotics, whereas the patient in Case 2 was only treated surgically. Both cases illustrate the doctor's delay in diagnosing mycobacterial infections, and remind us that nontuberculous mycobacterial infections should be part of the differential diagnosis of tenosynovitis, especially in immunocompromised patients.

Influence of social support among employees on mental health and work ability-a prospective cohort study in 2013-15.

Background: The study examined the association of social support with mental health, subjective work ability and psychological consultation. Methods: The cohort study included 1886 German employees (40-54 years) with sickness absence exceeding six weeks in 2012. Postal surveys were carried out in 2013 and 2015. Results: After adjustment for socio-demographic data, work-related characteristics and personality factors, persons with low social support compared to high social support had poorer mental health (b=-4.96; 95% CI: -7.11 to -2.81) and a lower work ability index (b=-1.10; 95% CI -2.00 to -0.21). Low social support was not associated with increased odds of consulting a psychologist (OR =1.30; 95% CI: 0.86-1.96). Conclusions: Low social support is an independent predictor of poorer mental health and lower work ability. This study highlights the importance of identifying people who have limited access to social support.

Self-Reported Work Ability Predicts Rehabilitation Measures, Disability Pensions, Other Welfare Benefits, and Work Participation: Longitudinal Findings from a Sample of German Employees.

Purpose The study examined the performance of the Work Ability Index in predicting rehabilitation measures and disability pensions, sickness absence and unemployment benefits, and work participation among a sample of workers previously receiving sickness absence benefits. Methods Workers aged 40 to 54 years who received sickness absence benefits in 2012 completed the Work Ability Index in 2013. Outcomes were extracted from administrative data records. Results Data for 2149 participants were included (mean age: 47.8 years; 54.4% women). Mean follow-up was 19 months. Work Ability Index scores were poor (7-27 points) in 21% of the participants, and moderate (28-36 points) in 38.4%. In all, 224 rehabilitation measures and 35 disability pensions were approved. Fully adjusted analyses showed increased risk of rehabilitation measures in workers with poor (HR 4.55; 95% CI 3.14-6.60) and moderate scores (HR 2.08; 95% CI 1.43-3.01) compared to workers with good or excellent scores (37-49 points). The risk of a disability pension increased significantly for workers with poor scores (HR 7.78; 95% CI 2.59-23.35). In addition, poor scores were prospectively associated with a longer duration of sickness absence and employment benefits, and fewer employment days and less income from regular employment. Conclusions The Work Ability Index is a potential tool for following up workers who already have an increased risk of permanent work disability due to previous long-term sickness absence.

Associations between organizational injustice and work ability, self-reported disability days, and medical consultations: cross-sectional findings from employees with prior sickness absence payments.

PURPOSE: The aim of the study was to identify associations between organizational injustice and work ability, disability days, and consultations with general practitioners. METHODS: Cross-sectional data of persons previously receiving sickness absence benefits were used for analyses. Organizational injustice was assessed using a German version of the "organizational justice questionnaire". Dependent variables were the Work Ability Index, self-reported disability days, and consultations with general practitioners. Associations were adjusted for sociodemographic characteristics, behavioral health risks, neuroticism, effort-reward imbalance, and overcommitment. RESULTS: The analysis included 2983 employed persons (54.1% women, mean age: 47.9 years). High organizational injustice was associated with poor work ability (OR = 2.04, 95% CI 1.55-2.69). There were also slight associations with frequent self-reported disability days (OR = 1.34, 95% CI 1.06-1.68). The dependent variables were also associated with the effort-reward ratio and overcommitment. CONCLUSION: Organizational injustice is associated with work ability, self-reported disability days, and health-care utilization. Results support the notion of a complementary role of the models of organizational justice and effort-reward imbalance.

[Occupational Health Physicians and Rehabilitation - A Cross-sectional Study on Occupational Health Care in Schleswig-Holstein and Baden-Württemberg]. / Betriebsärzte und Rehabilitation ­ Eine Querschnittsstudie zum betriebsärztlichen Handeln in Schleswig-Holstein und Baden-Württemberg.

Objective Description and explanation of involvement of occupational health physicians in rehabilitation Methods Data were collected by a survey of occupational health physicians in Schleswig-Holstein and Baden-Württemberg. Logistic regression models were calculated to identify determinants of the involvement of occupational health physicians before, during and after rehabilitation. Results During the last year 70% of the occupational health physicians have supported at least one worker when applying for medical rehabilitation. About a half has had at least once contact to a rehabilitation facility during the rehabilitation treatment of an employee, and 9 out of 10 physicians have supported at least one employee after her or his rehabilitation when returning to work. Support by occupational health physicians is more likely when they feel responsible for rehabilitation, are well informed and frequently involved in occupational reintegration management. Conclusions Occupational health physicians may be important stakeholders for preparing and supporting rehabilitation.

[Motivational and Volitional Processes in the Context of Applying for Medical Rehabilitation Services]. / Motivationale und volitionale Prozesse im Kontext der Beantragung einer medizinischen Rehabilitationsleistung.

OBJECTIVES: We analyzed if intention and planning of an application for medical rehabilitation can be described using the health action process approach. MATERIAL AND METHODS: Data were used from the "Third German Sociomedical Panel of Employees". A questionnaire comprising 8 scales was developed. The scales assess outcome expectancies (3 scales), support by family and physicians (2 scales), self-efficacy, intention and action planning (1 scale each). A confirmatory factor analysis was performed to examine the factorial validity of the questionnaire. Structural equation modeling was used to explain intention and planning of an application for medical rehabilitation. RESULTS: 3 294 persons participated in the survey. The average age was 47.9 years (range 40-54 years, SD=4.1). 53% of the participants were women. Further analyses included data of 2 911 (listwise deletion) and 3 288 participants (estimated missing values), respectively. The anticipated 8-factor structure of the questionnaire was confirmed. The model fit of the structural equation model was good. Intention was explained by family-related negative outcome expectancies, self-efficacy, and support by family and physicians. Intention and support by physicians directly affected planning. Additionally, family-related negative outcome expectancies, family and physician support, and self-efficacy were indirectly associated with planning. This indirect effect was mediated by intention. 51% of the variance of intention and 65% of the variance of planning were explained. DISCUSSION: The findings of the structural equation model indicate that the health action process approach is useful to describe the process of applying for medical rehabilitation. A validation of the model needs longitudinal data on actual applications. CONCLUSION: The health action process approach supports our understanding of motivational and volitional determinants of an application for medical rehabilitation. Our results underline the important role that family doctors and occupational physicians have if an application for medical rehabilitation is needed.

[Quality assurance follow-up survey of the ELISA cohort study on the prevalence of COVID-19: The view of study participants - What is well received?] / Nachbefragung zur Qualitätssicherung der ELISA-Kohortenstudie zur COVID-19-Prävalenz: Die Sicht von Studienteilnehmerinnen und Studienteilnehmern ­ Was kommt gut an?

INTRODUCTION: With the outbreak of the Corona pandemic, the LübEcker longitudinal study on infections with SARS-CoV-2 (ELISA study) was conducted in the Lübeck area to provide information on the prevalence, unreported cases and symptoms of COVID-19. The aim of the present study is to evaluate defined structure and process indictors of the study conduct of the ELISA study by subjects. METHODS: After defining and operationalizing participant-oriented quality indicators, 3,710 participants were surveyed online via LimeSurvey. Indicators defined were access to the study, time requirements, reporting of findings, ratings of the study apps used, communication, study center, tolerability of sample collection, and willingness to re-participate. In addition, comments on push and pull factors of study participation could be made. The evaluation was both quantitative and qualitative. RESULTS: 45% of the follow-up respondents (n=1,684) answered the questions on the defined structural and process indicators. In the quantitative part of the survey, tolerability of venous blood sampling was rated as significantly better than that of nasopharyngeal smears. 91% of the follow-up respondents welcomed the offer to view their findings in the personal results portal. Overall, the indicators were mostly rated positively. According to the qualitative data, the study participants found the win-win situation of the test opportunity to contribute to research, the local relevance of the study, the small incentives, and the low-threshold nature of the study registration to be positive aspects of the study. According to the quantitative data, participants suggested improving the usability of the digital applications in terms of more user-friendly identification solutions, reminder functions, announcements of software updates and avoidance of double entries. DISCUSSION: The defined structure and process indicators appear to be suitable for assessing the quality of study implementation from the subjects' point of view and indicate a good quality of study implementation under pandemic conditions. The lowest participation rate (75%) was measured at the fifth test time of strongly declining COVID-19 infections during the summer holidays in Schleswig-Holstein. Obviously, the benefit and meaningfulness of further study participation as well as competing factors were weighted differently by the subjects at this point. The follow-up survey suggests a variety of options for motivating participants to maintain a high level of participation. Possible limitations are that a non-response bias cannot be excluded for the follow-up survey and that no suitable standardised questionnaire was available. CONCLUSION: The present study provides recommendations for the planning of future cohort studies. It makes sense to continuously evaluate the motives for participation or non-participation and to explicitly consider them in the course of the study. Therefore, the definition of general quality indicators for the practical implementation of studies seems desirable. Positive experiences of the participants in connection with study participation are important, such as good time management, short response times, technical support offers and additional services such as a study homepage with frequently asked questions (FAQs), timely individual notifications of results and transparent, generally understandable information about study results during the study. Digital solutions are well received, but can still be improved for specific studies.

One-year surveillance of SARS-CoV-2 transmission of the ELISA cohort: A model for population-based monitoring of infection risk.

With newly rising coronavirus disease 2019 (COVID-19) cases, important data gaps remain on (i) long-term dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates in fixed cohorts (ii) identification of risk factors, and (iii) establishment of effective surveillance strategies. By polymerase chain reaction and antibody testing of 1% of the local population and >90,000 app-based datasets, the present study surveilled a catchment area of 300,000 inhabitants from March 2020 to February 2021. Cohort (56% female; mean age, 45.6 years) retention was 75 to 98%. Increased risk for seropositivity was detected in several high-exposure groups, especially nurses. Unreported infections dropped from 92 to 29% during the study. "Contact to COVID-19-affected" was the strongest risk factor, whereas public transportation, having children in school, or tourism did not affect infection rates. With the first SARS-CoV-2 cohort study, we provide a transferable model for effective surveillance, enabling monitoring of reinfection rates and increased preparedness for future pandemics.

[Stress, coping strategies and health-related quality of life during the corona pandemic in April 2020 in Germany]. / Stress, Copingstrategien und gesundheitsbezogene Lebensqualität während der Corona-Pandemie im April 2020 in Deutschland.

INTRODUCTION: International studies indicate that pandemics and quarantine can lead to significantly increased stress levels and mental illness in those affected. Stress levels and quality of life in selected population groups in the early phase of the lockdown of the corona pandemic were examined. Associations of coping strategies with perceived stress levels and associations of activities to increase well-being with health-related quality of life as an aspect of well-being are presented. METHODS: Data from the first survey wave of the CoPa study were evaluated, which were collected via online survey. Group differences regarding stress and quality of life were explorative tested by means of Chi-square tests and T-tests. Associations of coping strategies with stress and of activities to increase well-being with health-related quality of life were calculated using linear regression analysis. RESULTS: Among the 5315 participants, persons at risk of mental health and those who did not go out in public showed signs of depression, anxiety disorders and stress significantly more often than other participants. Persons with children under 12 years of age showed significantly higher stress levels than others and their health-related quality of life was comparable. Perceived social support and self-efficacy proved to be resources for stress. Humor, physical activity, healthy eating, maintaining daily routines and pursuing specific goals were positively associated with health-related quality of life. DISCUSSION: Persons with mental health risks need therapeutic services in times of reduced contact. Selected measures to increase well-being appear to be effective and should be recommended.

Prognostic impact of histological review of high-grade endometrial carcinomas in a large Danish cohort.

The aim of this study was to investigate the outcome of histological subtype review of high-grade endometrial carcinoma (EC) and its prognostic impact in a large well-documented Danish nationwide cohort. From the Danish Gynecological Cancer Database (DGCD) 2005-2012 cohort, we included 425 patients with an original diagnosis of high-grade EC, independent of histologic subtype. Of these, at least one hematoxylin and eosin (H&E)-stained slide from 396 cases (93.2%) was available for review. The histologic subtype was reviewed by specialized gynecopathologists blinded to the original diagnosis and clinical outcome. Interobserver variability between original and revised histologic subtypes was analyzed using simple Kappa statistics. Hazard ratios (HR), recurrence-free survival (RFS), and overall survival were calculated for original and revised subtypes, respectively. Overall histologic subtype agreement was moderate (kappa = 0.42) with the highest agreement for endometrioid-type EC (EEC; 75.5%) and serous-type EC (SEC; 63.8%). For clear cell carcinoma and un-/dedifferentiated EC, agreement was significantly lower: 30.1% and 33.3% respectively. Of the 396 reviewed cases, only two (0.5%) were re-classified as low-grade EEC upon revision. Interestingly, GR3 EEC had better RFS than SEC with stronger significance after revision (HR 2.36 (95% CI 1.43-3.89), p = 0.001), compared to original diagnosis (HR 1.74 (95% CI 1.07-2.81), p = 0.024). In conclusion, this study confirmed that pathology review results in substantial shift in histological subtype in high-grade EC. After review, a stronger prognostic benefit for GR3 EEC as compared to other histological subtypes was observed. This work supports maintaining a low threshold for pathology revision of high-grade EC in clinical practice.

Projection of Morbidity 2030 and 2050: Impact for the National Health System and Blood Supply.

BACKGROUND: The German population will decrease by 16% until 2050, and the ratio of young to old people is shifting towards the elderly. Because risk of disease rises with age, an aging society will be confronted with a higher burden of diseases. METHODS: A projection of status quo case numbers and crude rates of selected diseases was done for the years 2030 and 2050. Actual sex- and age-specific rates were transferred to the predicted population figures (11th coordinated population prediction). RESULTS: Cancer incidence will rise from 461,000 (2007) to 588,000 cases (2050) (+27%). Crude incidence rate will increase by 52%. Number of femoral neck fractures will rise by 88% (rate +122%). For other diseases incidence and prevalence will increase up to 144%. CONCLUSION: Blood (products) will be necessary for the therapy of many of the presented diseases. Therefore, it can be assumed that future demand of blood will rise in a similar manner as the rising number of diseases. The projected developments describe an extraordinary challenge for the German health care system and in particular for transfusion medicine. It is necessary to develop new concepts to meet this future demands and to ensure a high-performance health care system.

Effects of galanin and leptin on gonadotropin-releasing hormone-stimulated luteinizing hormone release from the pituitary.

BACKGROUND: A number of peptides regulate luteinizing hormone (LH) release. In some cases, these peptides exert an effect at the pituitary, to directly regulate LH release and/or to modulate the effects of gonadotropin-releasing hormone (GnRH). A link between nutrition and reproductive function is well established. In this study we investigated the effects of two peptides associated with appetite control, galanin and leptin, on the regulation of LH release from the pituitary. METHODS: Using perifused anterior pituitary tissue from freely fed rats, we investigated the effect of galanin on basal LH release and GnRH-stimulated LH release from pituitaries in a high-estrogen (proestrus) and a low-estrogen (metestrus) environment. In addition, we examined the effect of galanin on LH release following GnRH self-priming. The effect of inhibiting protein synthesis, with cycloheximide, was also studied under these conditions. Finally, the effects of leptin alone and on a galanin-modulated LH response were investigated. RESULTS: There was no detectable effect of leptin, either alone or in conjunction with galanin. We observed that galanin enhanced GnRH stimulation of LH secretion, an effect that was dependent on protein synthesis and on an estrogenized environment. In addition, importantly, galanin also enhanced the LH response in GnRH self-primed pulses. CONCLUSION: Our results provide further details on the effect of galanin on the LH surge, particularly the effect on the response to pulsatile GnRH and the effect of protein production, and thereby indicate a means by which appetite- and nutrition-related peptides may act on the ovulatory cycle at the pituitary.

Injustice at work affects work ability and role functioning: findings of a cohort study.

OBJECTIVES: The aim was to analyze the longitudinal effects of organizational injustice (OIJ) and effort-reward imbalance (ERI) on work ability, emotional role functioning and physical role functioning. METHODS: Longitudinal data with a two-year follow-up of people previously receiving sickness absence benefits were used for analyses. OIJ and ERI were included separately and mutually in logistic regression models. Effects were tested for additivity. All analyses were additionally performed stratified by sex. All models were adjusted for sociodemographics and neuroticism. RESULTS: 1886 participants (44.5% men, mean age: 48 years) were included. When mutually adjusted, OIJ and ERI affected work ability, and OIJ affected emotional role functioning. In stratified analyses, OIJ affected all outcomes in women, and ERI affected work ability in men. Additive effects of OIJ and ERI were not identified. CONCLUSIONS: OIJ and ERI are important risk factors of limited participation. People with experiences of health-related and work-related impairments are in need of reliable structures and just working conditions.

Vasculitis in Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia: A Report of Two Cases.

There is a clear association between myelodysplastic syndrome (MDS)/chronic myelomonocytic leukemia (CMML) and autoimmune manifestations such as vasculitis. It is not clear if autoimmune manifestations in myelodysplastic syndrome are a cause or consequence. We describe two patients with polyarteritis nodosa and large vessel vasculitis, as presenting symptom of a myelodysplastic syndrome with excess blasts type 2 and chronic myelomonocytic leukemia respectively. Immunosuppressive treatment resulted in amelioration of the vasculitis with improvement of the myelodysplastic features in the first patient and rapid evolution to acute myeloid leukemia in the other patient. The association between MDS/CMML and autoimmune manifestations, such as vasculitis, emphasizes the role of autoimmunity in the clinical features and even pathogenesis of MDS/CMML.