Lyme borreliosis in Finland: a register-based linkage study

BackgroundIn Finland, the routine surveillance of Lyme borreliosis (LB) is laboratory-based. In addition, we have well established national health care registers where countrywide data from patient visits in public health care units are collected. In our previous study based on these registers, we reported an increasing incidence of both microbiologically confirmed and clinically diagnosed LB cases in Finland during the past years. Here, we evaluated our register data, refined LB incidence estimates provided in our previous study, and evaluated treatment practices considering LB in the primary health care.MethodsThree national health care registers were used. The Register for Primary Health Care Visits (Avohilmo) and the National Hospital Discharge Register (Hilmo) collect physician-recorded data from the outpatient and inpatient health care visits, respectively, whereas the National Infectious Diseases Register (NIDR) represents positive findings in LB diagnostics notified electronically by microbiological laboratories. We used a personal identification number in register-linkage to identify LB cases on an individual level in the study year 2014. In addition, antibiotic purchase data was retrieved from the Finnish Social Insurance Institution in order to evaluate the LB treatment practices in the primary health care in Finland.ResultsAvohilmo was found to be useful in monitoring clinically diagnosed LB (i.e. erythema migrans (EM) infections), whereas Hilmo did not add much value next to existing laboratory-based surveillance of disseminated LB. However, Hilmo gave valuable information about uncertainties related to physician-based surveillance of disseminated LB and the total annual number of EM infections in our country. Antibiotic purchases associated with the LB-related outpatient visits in the primary health care indicated a good compliance with the recommended treatment guidelines.ConclusionsAvohilmo and laboratory-based NIDR together are useful in monitoring LB incidence in Finland. A good compliance was observed with the recommended treatment guidelines of clinically diagnosed LB in the primary health care. In 2018, Avohilmo was introduced in the routine surveillance of LB in Finland next to laboratory-based surveillance of disseminated LB

External validation of a model to predict the survival of patients presenting with a spinal epidural metastasis

The surgical treatment of spinal metastases is evolving. The major problem is the selection of patients who may benefit from surgical treatment. One of the criteria is an expected survival of at least 3 months. A prediction model has been previously developed. The present study has been performed in order to validate externally the model and to demonstrate that this model can be generalized to other institutions and other countries than the Netherlands. Data of 356 patients from five centers in Germany, Spain, Sweden, and the Netherlands who were treated for metastatic epidural spinal cord compression were collected. Hazard ratios in the test population corresponded with those of the developmental population. However, the observed and the expected survival were different. Analysis revealed that the baseline hazard function was significantly different. This tempted us to combine the data and develop a new prediction model. Estimating iteratively, a baseline hazard was composed. An adapted prediction model is presented. External validation of a prediction model revealed a difference in expected survival, although the relative contribution of the specific hazard ratios was the same as in the developmental population. This study emphasized the need to check the baseline hazard function in external validation. A new model has been developed using an estimated baseline hazar

IL-6 and other biomarkers as predictors of severity in COVID-19

ObjectiveCytokine release syndrome is suggested to be the most important mechanism triggering acute respiratory distress syndrome and end organ damage in COVID-19. The severity of disease may be measured by different biomarkers.MethodsWe studied markers of inflammation and coagulation as recorded in 29 patients on admission to the hospital in order to identify markers of severe COVID-19 and need of ICU.ResultsPatients who were eventually admitted to ICU displayed significantly higher serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin. No statistical differences were found between the groups in median levels of lymphocytes, D-dimer or ferritin.ConclusionsIL-6 and CRP were the strongest predictors of severity in hospitalized patients with COVID-19.</p

Interobserver reliability and diagnostic performance of Chiari II malformation measures in MR imaging—part 2

PURPOSE: Brain MR imaging is essential in the assessment of Chiari II malformation in clinical and research settings concerning spina bifida. However, the interpretation of MR images of the malformation is not always straightforward. Morphometric analyses of the extent of Chiari II malformation may improve the assessment. In an attempt to select appropriate morphometric measures for this purpose, we investigated the interobserver reliability and diagnostic performance of several morphometric measures of Chiari II malformation on MR images. METHODS: Brain MR images of 79 children [26 with open spinal dysraphism, 17 with closed spinal dysraphism, and 36 without spinal dysraphism; mean age 10.6 (SD 3.2; range, 6-16) years] were evaluated. All children had been assessed for Chiari II malformation (defined as cerebellar herniation in combination with open spinal dysraphism; n = 23). Three observers blindly and independently reviewed the MR images for 21 measures of the cerebellum, brainstem, and posterior fossa in three planes. The interobserver reliability was assessed by an agreement index (AI = 1 - RRE) and the diagnostic performance by receiver operating characteristic analyses. RESULTS: Reliability was good for most measures, except for the degree of herniation of the vermis and tonsil. Most values differed statistically significantly between children with and without Chiari II malformation. The measures mamillopontine distance and cerebellar width showed excellent diagnostic performance. CONCLUSIONS: Morphometric measures may reliably quantify the morphological distortions of Chiari II malformation on MR images and provide additional tools to assess the severity of Chiari II malformation in clinical and research settings

Intestinal Damage Determines the Inflammatory Response and Early Complications in Patients Receiving Conditioning for a Stem Cell Transplantation

Contains fulltext : 87954.pdf (publisher's version ) (Open Access)BACKGROUND: Stem cell transplantation (SCT) is still complicated by the occurrence of fever and inflammatory complications attributed to neutropenia and subsequent infectious complications. The role of mucosal barrier injury (MBI) of the intestinal tract therein has received little attention. METHODS: We performed a retrospective analysis in 163 SCT recipients of which data had been collected prospectively on intestinal damage (citrulline), inflammation (C-reactive protein), and neutrophil count. Six different conditioning regimens were studied; 5 myeloablative (MA) and 1 non-myeloablative (NMA). Linear mixed model multivariate and AUC analyses were used to define the role of intestinal damage in post-SCT inflammation. We also studied the relationship between the degree of intestinal damage and the occurrence of early post-SCT complications. RESULTS: In the 5 MA regimen there was a striking pattern of inflammatory response that coincided with the occurrence of severe intestinal damage. This contrasted with a modest inflammatory response seen in the NMA regimen in which intestinal damage was limited. With linear mixed model analysis the degree of intestinal damage was shown the most important determinant of the inflammatory response, and both neutropenia and bacteremia had only a minor impact. AUC analysis revealed a strong correlation between citrulline and CRP (Pearson correlation r = 0.96). Intestinal damage was associated with the occurrence of bacteremia and acute lung injury, and influenced the kinetics of acute graft-versus-host disease. CONCLUSION: The degree of intestinal damage after myeloablative conditioning appeared to be the most important determined the inflammatory response following SCT, and was associated with inflammatory complications. Studies should explore ways to ameliorate cytotoxic therapy-induced intestinal damage in order to reduce complications associated with myeloablative conditioning therapy

Erythema nodosum leprosum in Nepal: a retrospective study of clinical features and response to treatment with prednisolone or thalidomide.

Contains fulltext : 70372.pdf (publisher's version ) (Open Access)INTRODUCTION: Erythema nodosum leprosum (ENL) is an inflammatory reaction, which may occur in the course of leprosy and may result in nerve function impairment and subsequent disability. METHODS: This retrospective study explores demographic and disease specific parameters. Severity of ENL was assessed using the Reaction Severity Scale (RSS). Records of 94 patients were reviewed. The study reports also on the treatment of 76 of these patients who were treated with prednisolone alone or thalidomide in addition to prednisolone. RESULTS Thirty percent of patients presented with ENL at time of diagnosis; 41% developed ENL-reaction in the first year of MDT. Forty-eight percent of patients were treated for ENL-reaction for less than 12 months; 13% for more than 5 years. High RSS-scores correlated with a longer duration of treatment. In group A (prednisolone) 51.7% and in group B (prednisolone and thalidomide) 76.6% of patients were male. Age, leprosy classification, delay of multidrug treatment (MDT) and interval between MDT and first ENL-symptoms did not differ significantly in both groups. Median duration of ENL-treatment was 15 months in group A versus 38 months in group B (P < 0.001). At the start of treatment, ENL-reaction was less severe in group A (RSS = 12) than in group B (RSS = 18; P = 0.003). DISCUSSION: ENL-symptoms may be of help in the early diagnosis and adequate treatment of ENL. Characterisation of (sub) groups of patients with ENL based on presence and severity of symptoms is important for future prospective studies to better evaluate the efficacy of interventions

Lymphocytes and liver fibrosis in HIV & HCV coinfection

Coinfection with HIV has an important impact on immunity against hepatitis C virus (HCV). In the present dissertation, phenotypes of lymphocytes derived from the peripheral blood of HCV-infected patients were studied into detail, with special attention to changes in phenotype of lymphocytes associated with HIV-coinfection and liver fibrosis. HCV-infection was associated with increased apoptosis of T lymphocytes in comparison to healthy controls. HCV-infection was also associated with increased cell activation and exhaustion of T lymphocytes and this was correlated to the level of HCV-viraemia, suggesting that HCV directly causes non-specific T cell activation and exhaustion in the periphery. T lymphocyte apoptosis, activation and exhaustion were independent of liver fibrosis. Together these findings suggest that, if left untreated, HCV might on long term contribute to dysfunction of T lymphocytes through non-specific immune activation, even in the absence of liver fibrosis. Coinfection with HIV was associated with even higher levels of peripheral T lymphocyte activation than HCV monoinfection. Natural killer (NK) cells are a type of lymphocytes belonging to the innate immune system. Of the NK cell subsets, the CD56dim NK cells have generally been considered as the primarily cytotoxic subset, whereas CD56bright NK cells are thought to merely exert cytokine-producing activity. Surprisingly, Feuth et al demonstrate that CD56bright NK cells typically display high levels of the cytotoxic molecule FasL on their surface. Furthermore, chronic infection with HCV is associated with upregulation of FasL as well as with the cytotoxic molecules granzyme B and perforin. Liver fibrosis has traditionally been diagnosed by liver biopsy, an invasive method with rare but severe complications. Transient elastography has recently been implemented as an non-invasive measurement for liver fibrosis. A retrospective analysis, presented in this dissertation, demonstrated that transient elastography has major clinical impact on clinical decision-making concerning treatment and follow-up of patients with viral hepatitis. Lastly, the CD4/CD8 T cell ratio was identified as an alternative non-invasive marker for liver fibrosis in HCV monoinfection. If this finding is to be confirmed in larger studies, the marker might be of value especially in settings where transient elastography is not available. Altogether, the studies presented in this dissertation shed new light on regulation of innate and adaptive immunity in HCV monoinfection and HIV-HCV coinfection and identify CD4/CD8 T cell ratio as a promising non-invasive marker of liver fibrosis in HCV monoinfection

Early detection of myocardial dysfunction in children with mitochondrial disease: An ultrasound and two-dimensional strain echocardiography study

Item does not contain fulltextBACKGROUND: Myocardial dysfunction in children diagnosed with mitochondrial disease is an ominous sign and has been associated with substantial increased mortality rates. Early detection of cardiac involvement would therefore be desirable. Two dimensional strain echocardiography (2DSTE) has proven to be more sensitive than conventional echocardiography for the detection of early myocardial dysfunction in various (cardiac) conditions. AIMS: To determine left ventricular systolic function in children with mitochondrial disorders by means of physical examination, electrocardiography (ECG), conventional echocardiography and 2DSTE. METHODS: A total of 27 children with established mitochondrial disease and 54 age-matched control subjects underwent cardiac evaluation. Longitudinal, circumferential and radial peak systolic strain (S) values were determined as well as peak systolic strain rate (Sr) and the time to peak global systolic strain (T2P). One Way analysis of Variance was performed to assess the influence of the presence of mitochondrial disease on conventional echocardiographic and 2DSTE outcomes. RESULTS: Conventional echocardiographic findings did not indicate systolic left ventricular dysfunction. Global peak S, Sr and T2P measurements in all three directions were significantly lower in children with mitochondrial disease (P<0.001) when compared to controls. CONCLUSION: 2DSTE detects alterations in myocardial systolic function in children diagnosed with mitochondrial disease, whose conventional echocardiographic findings did not indicate ventricular systolic dysfunction

Eustachian tube function before recurrence of otitis media with effusion.

Contains fulltext : 47450.pdf (publisher's version ) (Closed access)OBJECTIVE: To study the role of eustachian tube function in the development of recurrent otitis media with effusion (OME) in children treated with tympanostomy tubes for OME. DESIGN: Prospective cohort study. SETTING: Three academic and general hospitals. PATIENTS: Children aged 2 to 7 years with a first clinical episode of OME that persisted for at least 3 months; 136 (81%) of 168 eligible children participated. All children received tympanostomy tubes for bilateral OME at study entry. MAIN OUTCOME MEASURE: Recurrence of OME within 6 months of tube extrusion. RESULTS: No statistically significant differences were present in eustachian tube function test results between ears that developed recurrent OME and those that did not. The difference in passive ventilatory function between ears with and without OME recurrence was 10 daPa (95% confidence interval, -24 to 43 daPa) for opening pressure and -3 daPa (95% confidence interval, -18 to 11 daPa) for closing pressure. The overall difference in the proportion of ears with and without OME recurrence that could not equilibrate positive and negative applied pressures was 12% (95% confidence interval, -2% to 26%). The proportions of ears with and without OME recurrence that induced negative pressure in the middle ear by forcefully sniffing were 22% and 31%, respectively (P = .75). CONCLUSION: Measurement of ventilatory and protective eustachian tube function using the forced response test, the pressure equilibration test, and the sniff test has no value in predicting whether children have an increased risk of OME recurrence

Reference values for myocardial two-dimensional strain echocardiography in a healthy pediatric and young adult cohort

BACKGROUND: The accurate evaluation of intrinsic myocardial contractility in children with or without congenital heart disease (CHD) has turned out to be a challenge. Two-dimensional strain echocardiographic (2DSTE) imaging or two-dimensional speckle-tracking echocardiographic imaging appears to hold significant promise as a tool to improve the assessment of ventricular myocardial function. The aim of this study was to estimate left ventricular myocardial systolic function using 2DSTE imaging in a large cohort consisting of healthy children and young adults to establish reference strain values. METHODS: Transthoracic echocardiograms were acquired in 195 healthy subjects (139 children, 56 young adults) and were retrospectively analyzed. Longitudinal, circumferential, and radial peak systolic strain values were determined by means of speckle tracking. Nonlinear regression analysis was performed to assess the effect of aging on these 2DSTE parameters. RESULTS: There was a strong, statistically significant second-order polynomial relation (P < .001) between global peak systolic strain parameters and age. Global peak systolic strain values were lowest in the youngest and oldest age groups. CONCLUSION: This is the first report to establish age-dependent reference values per cardiac segment for myocardial strain in all three directions assessed using 2DSTE imaging in a large pediatric and young adult cohort. There is a need to use age-specific reference values for the adequate interpretation of 2DSTE measurements