Interleukin-10 negatively regulates local cytokine and chemokine production but does not influence antibacterial host defense during murine pneumococcal meningitis.

To determine the role of endogenous interleukin-10 (IL-10) in local host defense during pneumococcal meningitis, the inflammatory responses of IL-10-gene-deficient and wild-type mice after the induction of meningitis were compared. The absence of IL-10 was associated with higher cytokine and chemokine concentrations and a more pronounced infiltrate, but antibacterial defense or survival was not influenced

How non-functioning pituitary adenomas can affect health-related quality of life: a conceptual model and literature review

After treatment for a non-functioning pituitary adenoma (NFA) health-related quality of life (HR-QoL) improves considerably. However, the literature about the normalization of HR-QoL after treatment is inconclusive. Some researchers described a persistently decreased HR-QoL compared to reference data, while others did not. Considering this variety in observed HR-QoL outcomes, the aim of the present review was to provide a literature overview of health outcomes in patients with a NFA, using a conceptual HR-QoL model. A concrete conceptualization of the health outcomes of patients with a NFA can be helpful to understand the observed variety in HR-QoL outcomes and to improve clinical care and guidance of these patients. For this conceptualization, the Wilson and Cleary model was used. This model has a biopsychosocial character and has been validated in several patient populations. In the present review, health outcomes of patients with a NFA were described at each stage of the model e.g. biological and physiological variables, symptom status, functional status, general health perceptions and overall HR-QoL. The Wilson-Cleary model elucidates that elements at each stage of the model can contribute to the impairment in HR-QoL of patients with a NFA, which explains the reported variety in the literature. Furthermore, by applying the model, potential interventions targeting these elements can be identified. While optimal biomedical treatment has always been the focus, it is clearly not sufficient for good HR-QoL in patients with a NFA. Further improvement of HR-QoL should be supported by a pituitary specific care trajectory, including psychosocial care (e.g. self-management training), to beneficially affect characteristics of the patient and the (healthcare) environment, with the utmost goal to optimize HR-QoL in patients after treatment.Diabetes mellitus: pathophysiological changes and therap

The church and paediatric HIV care in rural South Africa

Religion has substantial – positive and negative – influence on South Africa’s HIV context. This qualitative study explored possibilities for positive church engagement in paediatric HIV care in a rural district in Limpopo Province, South Africa. Opinions, attitudes and experiences of various stakeholders including religious leaders, healthcare workers and people infected/affected with/by HIV were investigated through participant observation, semi-structured interviews and focus group discussions. During the research the original focus on paediatric HIV care shifted to HIV care in general in reaction to participant responses. Participants identified three main barriers to positive church engagement in HIV care: (a) stigma and disclosure; (b) sexual associations with HIV and (c) religious beliefs and practices. All participant groups appreciated the opportunity and relevance of strengthening church involvement in HIV care. Opportunities for positive church engagement in HIV care that participants identified included: (a) comprehensive and holistic HIV care when churches and clinics collaborate; (b) the wide social reach of churches and (c) the safety and acceptance in churches. Findings indicate that despite barriers great potential exists for increased positive church engagement in HIV care in rural South Africa. Recommendations include increased medical knowledge and dialogue on HIV/AIDS within church settings, and increased collaboration between churches and the medical sector

Study protocol: The Dutch 20|30 Postmeningitis study: a cross-sectional follow-up of two historical childhood bacterial meningitis cohorts on long-term outcomes

BACKGROUND: Bacterial meningitis (BM) is a serious, life-threatening infectious disease of the central nervous system that often occurs in young children. The most common severe to moderate sequelae following BM are sensorineural hearing loss, neuromotor disabilities and mental retardation, while subtle sequelae include academic and behavioral disabilities. It is largely unknown whether these more subtle sequelae persist into adolescence and adulthood. Therefore, this study will investigate the very long-term effects of childhood BM in later life. Better understanding of long-term effects and early identification of adverse outcomes after BM are essential for more timely interventions. Additionally, certain single nucleotide polymorphisms (SNPs) are associated with disease severity and might predict adverse sequelae. These include SNPs in genes encoding for pathogen recognition and immune response upon infection. Accordingly, a secondary objective of this study is to investigate the role of genetic variation in BM and use any insights to predict short- and long-term outcomes. METHODS: In the Dutch 20|30 Postmeningitis study, adolescents and young adults (n = 947) from two historical cohorts with a prior episode of BM during childhood will be enrolled into a cross-sectional follow-up investigation using mainly questionnaires that examine executive and behavioral functioning, health-related quality of life, subjective hearing, mood and sleeping disorders, academic performance, and economic self-sufficiency. The results will be compared to normative data by one-sample t-tests. Multivariable regression analysis will be used to assess for any associations with causative pathogens and severity of BM. Participants that complete the questionnaires will be approached to provide a swab for buccal DNA and subsequent sequencing analyses. Logistic regression models will be used to predict sequelae. DISCUSSION: The unique follow-up duration of this cohort will enable us to gain insights into the possible very long-term adverse effects of childhood BM and how these might impact on quality of life. The investigation of host genetic factors will contribute to the development of prediction models which will serve as prognostic tools to identify children who are at high risk of adverse outcome after BM. TRIAL REGISTRATION: Dutch Trial Register NTR-6891. Retrospectively registered 28 December 2017

Improvement in symptoms and health-related quality of life in acromegaly patients: a systematic review and meta-analysis

Background: Whereas biochemical response is often used as a primary study outcome, improvement in symptoms and health-related quality of life (HRQoL) is the relevant goal for patients to consider treatment successful. We performed a systematic review and meta-analysis to assess the effect of treatment on symptoms and HRQoL in acromegaly.Methods: Seven electronic databases were searched for longitudinal studies assessing patient-reported symptoms or HRQoL in acromegaly. Meta-analyses were performed to assess differences during treatment for the Acromegaly Quality of Life Questionnaire (AcroQoL) and Patient-Assessed Acromegaly Symptom Questionnaire (PASQ), and standardized mean difference (SMD) for individual symptoms (interpretation: 0.2 small, 0.5 moderate, and 0.8 large effect). Treatment-naive and previously treated patients were assessed separately.Results: Forty-six studies with 3301 patients were included; 24 contributed to quantitative analyses. Thirty-six studies used medication as main treatment, 1 transsphenoidal adenomectomy, and 9 various treatments. Symptoms and HRQoL both improved: AcroQoL increased 2.9 points (95% CI, 0.5 to 5.3 points), PASQ decreased -2.3 points (95% CI, -1.3 to -3.3 points), and individual symptom scores decreased for paresthesia -0.9 (95% CI, -0.6 to -1.2), hyperhidrosis -0.4 (95% CI, -0.1 to -0.6), fatigue -0.3 (95% CI, -0.1 to -0.6), arthralgia -0.3 (95% CI, -0.1 to -0.5), headache -0.3 (95% CI, 0.0 to -0.6), and soft-tissue swelling -0.2 (95% CI, 0.0 to -0.4).Conclusion: Symptoms and HRQoL improved during acromegaly treatment. Consensus is needed on which symptoms should be included in a potential core outcome set, taking into account symptom frequency, severity, and sensitivity to change, which can be used in clinical practice and as outcome in trials.Clinical epidemiolog

Postoperative diabetes insipidus: how to define and grade this complication?

Purpose Although transient diabetes insipidus (DI) is the most common complication of pituitary surgery, there is no consensus on its definition. Polyuria is the most overt symptoms of DI, but can also reflect several physiological adaptive mechanisms in the postoperative phase. These may be difficult to distinguish from and might coincide with DI. The difficulty to distinguish DI from other causes of postoperative polyuria might explain the high variation in incidence rates. This limits interpretation of outcomes, in particular complication rates between centers, and may lead to unnecessary treatment. Aim of this review is to determine a pathophysiologically sound and practical definition of DI for uniform outcome evaluations and treatment recommendations. Methods This study incorporates actual data and the experience of our center and combines this with a review of literature on pathophysiological mechanisms and definitions used in clinical studies reporting of postoperative DI. Results The occurrence of excessive thirst and/or hyperosmolality or hypernatremia are the best indicators to discriminate between pathophysiological symptoms and signs of DI and other causes. Urine osmolality distinguishes DI from osmotic diuresis. Conclusions To improve reliability and comparability we propose the following definition for postoperative DI: polyuria (urine production > 300 ml/hour for 3 h) accompanied by a urine specific gravity (USG) 300 mosmol/kg, or serum sodium > 145 mmol/L. To prevent unnecessary treatment with desmopressin, we present an algorithm for the diagnosis and treatment of postoperative DI.Diabetes mellitus: pathophysiological changes and therap

Endoscopic vs. microscopic transsphenoidal surgery for Cushing's disease: a systematic review and meta-analysis

Clinical epidemiolog

State of the art of patient-reported outcomes in acromegaly or GH deficiency: a systematic review and meta-analysis

Metabolic health: pathophysiological trajectories and therap

Progression of vertebral fractures in long-term controlled acromegaly: a 9-year follow-up study

Objective: Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) excess results in both reversible and irreversible musculoskeletal damage, including increased vertebral fracture (VF) risk. The prevalence of VFs is approximately 60% in controlled acromegaly patients, and these VFs can progress in time. We aimed to identify the course of VFs in a cohort of acromegaly patients in long-term remission and their associated risk factors during prolonged follow-up.Methods: Thirty-one patients with acromegaly (49% female, median age 60 years (IQR 53-66)), who were in remission for >= 2 years, were included in this longitudinal, prospective, follow-up study. Spine radiographs of vertebrae Th4 to L4 were assessed for VFs using the Genant score, at baseline, after 2.6 years and 9.1 years. Progression was defined as either a new fracture or a >= 1-point increase in Genant score.Results: The prevalence of VF at baseline was 87% (27/31 patients). Progression of VFs was observed in eleven patients (35.5%) during the 9.1-year follow-up period, with a total incidence rate of 65.5 per 1000 person years (males 59.8 per 1000 person years vs females 71.6 per 1000 person years). Patients treated with surgery or radiotherapy had a higher risk of VF progression in this cohort (P = 0.030).Conclusions: In this cohort of long-term, well-controlled acromegalic patients, the prevalence and progression of VFs was high, showing that the deleterious effects of GH and IGF-1 excess on bone persist despite achievement of longstanding remission.Diabetes mellitus: pathophysiological changes and therap