Machine learning-based immune phenotypes correlate with STK11/KEAP1 co-mutations and prognosis in resectable NSCLC: a sub-study of the TNM-I trial.

BACKGROUND: We aim to implement an immune cell score model in routine clinical practice for resected non-small-cell lung cancer (NSCLC) patients (NCT03299478). Molecular and genomic features associated with immune phenotypes in NSCLC have not been explored in detail. PATIENTS AND METHODS: We developed a machine learning (ML)-based model to classify tumors into one of three categories: inflamed, altered, and desert, based on the spatial distribution of CD8+ T cells in two prospective (n = 453; TNM-I trial) and retrospective (n = 481) stage I-IIIA NSCLC surgical cohorts. NanoString assays and targeted gene panel sequencing were used to evaluate the association of gene expression and mutations with immune phenotypes. RESULTS: Among the total of 934 patients, 24.4% of tumors were classified as inflamed, 51.3% as altered, and 24.3% as desert. There were significant associations between ML-derived immune phenotypes and adaptive immunity gene expression signatures. We identified a strong association of the nuclear factor-κB pathway and CD8+ T-cell exclusion through a positive enrichment in the desert phenotype. KEAP1 [odds ratio (OR) 0.27, Q = 0.02] and STK11 (OR 0.39, Q = 0.04) were significantly co-mutated in non-inflamed lung adenocarcinoma (LUAD) compared to the inflamed phenotype. In the retrospective cohort, the inflamed phenotype was an independent prognostic factor for prolonged disease-specific survival and time to recurrence (hazard ratio 0.61, P = 0.01 and 0.65, P = 0.02, respectively). CONCLUSIONS: ML-based immune phenotyping by spatial distribution of T cells in resected NSCLC is able to identify patients at greater risk of disease recurrence after surgical resection. LUADs with concurrent KEAP1 and STK11 mutations are enriched for altered and desert immune phenotypes.

Characterization of different endoscopic imaging systems in ultraviolet range for combustion applications.

Endoscopic optical diagnostics for IC engines offer the advantage of retaining the full operating range and thermal properties of the production engine. The custom-designed modular hybrid UV endoscope system is optimized for application in IC engines.; however, its hybrid refractive/diffractive relay element is expensive and has a narrow operating wavelength range. To make the endoscopic imaging more universally applicable, the hybrid relay element of the mentioned endoscope system was replaced by commercial UV camera lenses, and several combinations were characterized in terms of resolution, brightness, and chromatic aberration. With an unintensified CCD camera, endoscope systems using commercial camera lenses had better resolution at investigated magnifications of 0.5 and 1. However, with an intensified camera, the system with the hybrid relay lens had the best overall performance in its design wavelength range. Selected imaging systems were used in a spark-ignition engine to image O H ∗-chemiluminescence, with results consistent with those from bench-top characterization.

Study protocol P-MAPS: microbiome as predictor of severity in acute pancreatitis-a prospective multicentre translational study.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disorder that causes a considerable economic health burden. While the overall mortality is low, around 20% of patients have a complicated course of disease resulting in increased morbidity and mortality. There is an emerging body of evidence that the microbiome exerts a crucial impact on the pathophysiology and course of AP. For several decades multiple clinical and laboratory parameters have been evaluated, and complex scoring systems were developed to predict the clinical course of AP upon admission. However, the majority of scoring systems are determined after several days and achieve a sensitivity around 70% for early prediction of severe AP. Thus, continued efforts are required to investigate reliable biomarkers for the early prediction of severity in order to guide early clinical management of AP patients. METHODS: We designed a multi-center, prospective clinical-translational study to test whether the orointestinal microbiome may serve as novel early predictor of the course, severity and outcome of patients with AP. We will recruit 400 AP patients and obtain buccal and rectal swabs within 72 h of admission to the hospital. Following DNA extraction, microbiome analysis will be performed using 3rd generation sequencing Oxford Nanopore Technologies (ONT) for 16S rRNA and metagenomic sequencing. Alpha- and beta-diversity will be determined and correlated to the revised Atlanta classification and additional clinical outcome parameters such as the length of hospital stay, number and type of complications, number of interventions and 30-day mortality. DISCUSSION: If AP patients show a distinct orointestinal microbiome dependent on the severity and course of the disease, microbiome sequencing could rapidly be implemented in the early clinical management of AP patients in the future. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04777812.

Higher levels of bodily pain in people with long-term type 1 diabetes: associations with quality of life, depressive symptoms, fatigue and glycaemic control - the Dialong study.

AIMS: To compare reported level of bodily pain, overall and health-related quality of life (QoL), depression and fatigue in people with long-term type 1 diabetes vs. a comparison group without diabetes. Further, to examine the associations of total bodily pain with QoL, depression, fatigue and glycaemic control in the diabetes group. METHODS: Cross-sectional study of 104 (76% of eligible) people with type 1 diabetes of ≥ 45 years' duration attending the Norwegian Diabetes Centre and 75 persons without diabetes who completed questionnaires measuring bodily pain (RAND-36 bodily pain domain), shoulder pain (Shoulder Pain and Disability Index), hand pain (Australian/Canadian Osteoarthritis Hand Index), overall QoL (World Health Organization Quality of Life - BREF), health-related QoL (RAND-36), diabetes-specific QoL (Audit of Diabetes-Dependent Quality of Life; only diabetes group), depression (Patient Health Questionnaire) and fatigue (Fatigue questionnaire). For people with type 1 diabetes, possible associations between the bodily pain domain (lower scores indicate higher levels of bodily pain) and other questionnaire scores, were measured with regression coefficients (B) per 10-unit increase in bodily pain score from linear regression. RESULTS: The diabetes group reported higher levels of bodily (P = 0.003), shoulder and hand pain (P < 0.001) than the comparison group. In the diabetes group, bodily pain was associated with lower overall and diabetes-specific QoL [B (95% confidence intervals)]: 0.2 (0.1, 0.2) and 0.2 (0.1, 0.3); higher levels of depression -1.0 (-1.3, -0.7) and total fatigue -1.5 (-1.9, -1.2); and worse glycaemic control HbA1c (mmol/mol; %) -0.8 (-1.5, -0.1); -0.1 (-0.1, -0.01). CONCLUSIONS: People with long-term type 1 diabetes experience a high level of bodily pain compared with a comparison group. Total bodily pain was associated with worse QoL and glycaemic control.

Variation in the achievement of HbA1c , blood pressure and LDL cholesterol targets in type 2 diabetes in general practice and characteristics associated with risk factor control.

AIMS: To identify population, general practitioner, and practice characteristics associated with the achievement of HbA1c , blood pressure and LDL cholesterol targets, and to describe variation in the achievement of risk factor control. METHODS: We conducted a cross-sectional survey of 9342 people with type 2 diabetes, 281 general practitioners and 77 general practices in Norway. Missing values (7.4%) were imputed using multiple imputation by chained equations. We used three-level logistic regression with the achievement of HbA1c , blood pressure and LDL cholesterol targets as dependent variables, and factors related to population, general practitioners, and practices as independent variables. RESULTS: Treatment targets were achieved for HbA1c in 64%, blood pressure in 50%, and LDL cholesterol in 52% of people with type 2 diabetes, and 17% met all three targets. There was substantial heterogeneity in target achievement among general practitioners and among practices; the estimated proportion of a GPs diabetes population at target was 55-73% (10-90 percentiles) for HbA1c , 36-63% for blood pressure, and 47-57% for LDL cholesterol targets. The models explained 11%, 5% and 14%, respectively, of the total variation in the achievement of HbA1c , blood pressure and LDL cholesterol targets. Use among general practitioners of a structured diabetes form was associated with 23% higher odds of achieving the HbA1c target (odds ratio 1.23, 95% confidence interval (CI) 1.02-1.47) and 17% higher odds of achieving the LDL cholesterol target (odds ratio 1.17, 95% CI 1.01-1.35). CONCLUSIONS: Clinical diabetes management is difficult, and few people meet all three risk factor control targets. The proportion of people reaching target varied among general practitioners and practices. Several population, general practitioner and practice characteristics only explained a small part of the total variation. The use of a structured diabetes form is recommended.

[Spectroscopic investigation of the middle ear mucosa]. / Spektroskopische Untersuchung der Mittelohrschleimhaut.

BACKGROUND: The middle ear mucosa (MEM) plays a central role in the middle ear due to its function of providing regular ventilation. To date, assessment of the state of the MEM is only possible subjectively by the surgeon. An objective characterization of the state of the MEM is desirable. OBJECTIVE: The aim of this study was to enable objective characterization of the MEM and test infrared (IR) spectroscopy as a possible diagnostic tool for clinical use. MATERIALS AND METHODS: During middle ear surgery, 48 MEM samples were collected and divided into four groups according to clinical appearance: group I: normal MEM; group II: sclerotic MEM; group III: inflammatory thickened MEM; group IV: granulated MEM. After collection, samples were analyzed by IR spectroscopy to identify characteristic IR spectra. RESULTS: In the supervised analysis of the selected images, the biochemical differences representing the decisive factors for classification into groups I to IV were characterized. The differences in amide bands, carbohydrates, lipids, and proteins permit reliable separation of the clinical categories. CONCLUSION: Spectroscopic investigations enable objective characterization of the MEM. Conclusions regarding biochemical differences make it possible to weigh up treatment options. Routine use of IR spectroscopy in the operating theater requires histopathological comparison and an extended dataset with reference values of the individual groups.

Plasma levels of the cardiovascular protective endogenous nucleoside adenosine are reduced in patients with primary aldosteronism without affecting ischaemia-reperfusion injury: A prospective case-control study.

BACKGROUND: Patients with primary aldosteronism (PA) experience more cardiovascular events compared to patients with essential hypertension (EHT), independent from blood pressure levels. In animals, mineralocorticoid receptor antagonists limit ischaemia-reperfusion (IR) injury by increasing extracellular adenosine formation and adenosine receptor stimulation. Adenosine is an endogenous compound with profound cardiovascular protective effects. Firstly, we hypothesized that patients with PA have lower circulating adenosine levels which might contribute to the observed increased cardiovascular risk. Secondly, we hypothesized that by this mechanism, patients with PA are more susceptible to IR compared to patients with EHT. DESIGN: In our prospective study in 20 patients with PA and 20 patients with EHT, circulating adenosine was measured using a pharmacological blocker solution that halts adenosine metabolism after blood drawing. Brachial artery flow-mediated dilation (FMD) before and after forearm IR was used as a well-established method to study IR injury. RESULTS: Patients with PA had a 33% lower adenosine level compared to patients with EHT (15.3 [13.3-20.4] vs 22.7 [19.4-36.8] nmol/L, respectively, P < .01). The reduction in FMD after IR, however, did not differ between patients with PA and patients with EHT (-1.0 ± 2.9% vs -1.6 ± 1.6%, respectively, P = .52). CONCLUSIONS: As adenosine receptor stimulation induces various powerful protective cardiovascular effects, its lower concentration in patients with PA might be an important novel mechanism that contributes to their increased cardiovascular risk. We suggest that modulation of the adenosine metabolism is an exciting novel pharmacological opportunity to limit cardiovascular risk in patients with PA that needs further exploration.

Population, general practitioner and practice characteristics are associated with screening procedures for microvascular complications in Type 2 diabetes care in Norway.

AIMS: To assess population, general practitioner (GP) and practice characteristics associated with the performance of microvascular screening procedures and to propose strategies to improve Type 2 diabetes care. METHODS: A cross-sectional survey in Norway (281 GPs from 77 practices) identified 8246 people with a Type 2 diabetes duration of 1 year or more. We used multilevel regression models with either the recording of at least two of three recommended screening procedures (albuminuria, monofilament, eye examination) or each procedure separately as dependent variable (yes/no), and characteristics related to the person with diabetes, GP or practice as independent variables. RESULTS: The performance of recommended screening procedures was recorded in the following percentages: albuminuria 31.5%, monofilament 27.5% and eye examination 60.0%. There was substantial heterogeneity between practices, and between GPs within practices for all procedures. Compared with people aged 60-69 years, those aged < 50 years were less likely to have an albuminuria test performed [odds ratio (OR) 0.75, 95% CI 0.61 to 0.93] and eye examination (OR 0.79, 95% CI 0.66 to 0.95). People with macrovascular disease had fewer screening procedures recorded (OR 0.68, 95% CI 0.59 to 0.78). Use of an electronic diabetes form was associated with improved screening  (OR 2.65, 95% CI 1.86 to 3.78). GPs with high workload recorded fewer procedures (OR 0.59, 95% CI 0.39 to 0.90). CONCLUSIONS: Performance of screening procedures was suboptimal overall, and in people who should be prioritized. Performance varied substantially between GPs and practices. The use of a structured diabetes form should be mandatory.

[Requirements for outpatient care after implantation of a ventricular assist device : Views of patients and their relatives]. / Anforderungen an die ambulante Versorgung nach Implantation eines ventrikulären Herzunterstützungssystems : Sichtweise von Patienten und Angehörigen.

Ventricular assist device (VAD) implantation has developed into a well-established option when conservative treatment of terminal heart failure has been exhausted. Figures from 2015 make this clear: only 283 heart transplantations were performed nationwide but 959 VAD systems were implanted. It is noteworthy that the survival times with a VAD are approaching the survival times after heart transplantation. Patients with VADs have a life-long dependency on their proximity to specialists. So far, the requirements for outpatient care have not been systematically recorded from the perspective of VAD patients and their relatives. In September 2016, VAD patients (n = 30) and their relatives (n = 25) were anonymously questioned about their views on postoperative outpatient care. For this purpose, the VAD Patient Satisfaction Survey was adapted to the needs of this study. Patients with VADs and their relatives were found to experience their daily life with a VAD in a positive manner. Information, training, accessibility and regular contacts with the implantation clinic and the VAD coordinator are important pillars of outpatient care after VAD implantation. Almost 95% of surveyed patients regarded good home support as an important factor that makes life with a VAD easier. These aspects should be taken into account in the care of patients living with a VAD.

The prevalence of radiological glenohumeral osteoarthritis in long-term type 1 diabetes: the Dialong shoulder study.

OBJECTIVES: This study compares the prevalence of radiological osteoarthritis (OA) in patients with type 1 diabetes mellitus (DM1) for > 45 years and controls, and explores the association with shoulder pain and glycaemic burden in patients with DM1. METHOD: The Dialong study is a cross-sectional, observational study with 30 years of historical data on long-term glycaemic control. We included 102 patients with DM1 and 73 diabetes-free controls. Demographic data, worst shoulder pain last week [numeric rating scale (NRS) 0-10], pain on abduction at examination (NRS 0-10), and current and historical glycosylated haemoglobin (HbA1c) levels were collected. Standardized shoulder X-rays were taken and interpreted for OA applying the Kellgren-Lawrence classification. RESULTS: In the diabetes group (49% women), the mean ± sd duration of DM1 was 50.6 ± 4.8 years, mean 30 year HbA1c 7.4%, and age 61.9 ± 7.1 years. The mean age of controls (57% women) was 62.6 ± 7.0 years. Radiological glenohumeral OA was found in 36 diabetes patients (35%) and 10 controls (14%) [odds ratio (OR) 3.4, 95% confidence interval (CI) 1.6 to 7.5; p = 0.002]. Few persons had moderate and severe OA [6.9% vs 1.3%, OR 5.3 (95% Cl 0.6 to 44.1); p = 0.1]. Fifteen diabetes patients had painful OA versus two controls (adjusted OR 5.4, 95% CI 0.6 to 47.9; p = 0.13). There was no association between OA and long-term glycaemic burden (mean 30 year HbA1c) in the diabetes group (p > 0.2). CONCLUSIONS: Radiological glenohumeral OA was more common in patients with DM1 than in controls for mild, but not moderate and severe OA. The radiological findings were not associated with shoulder pain or long-term glycaemic burden.

Surgical resection versus watchful waiting in low-grade gliomas.

BACKGROUND: Infiltrating low-grade gliomas (LGG; WHO grade 2) typically present with seizures in young adults. LGGs grow continuously and usually transform to higher grade of malignancy, eventually causing progressive disability and premature death. The effect of up-front surgery has been controversial and the impact of molecular biology on the effect of surgery is unknown. We now present long-term results of upfront surgical resection compared with watchful waiting in light of recently established molecular markers. MATERIALS AND METHODS: Population-based parallel cohorts were followed from two Norwegian university hospitals with different surgical treatment strategies and defined geographical catchment regions. In region A watchful waiting was favored while early resection was favored in region B. Thus, the treatment strategy in individual patients depended on their residential address. The inclusion criteria were histopathological diagnosis of supratentorial LGG from 1998 through 2009 in patients 18 years or older. Follow-up ended 1 January 2016. Making regional comparisons, the primary end-point was overall survival. RESULTS: A total of 153 patients (66 from region A, 87 from region B) were included. Early resection was carried out in 19 (29%) patients in region A compared with 75 (86%) patients in region B. Overall survival was 5.8 years (95% CI 4.5-7.2) in region A compared with 14.4 years (95% CI 10.4-18.5) in region B (P < 0.01). The effect of surgical strategy remained after adjustment for molecular markers (P = 0.001). CONCLUSION: In parallel population-based cohorts of LGGs, early surgical resection resulted in a clinical relevant survival benefit. The effect on survival persisted after adjustment for molecular markers.

Functional connectivity alterations in patients with chronic hepatitis C virus infection: A multimodal MRI study.

Chronic hepatitis C virus (HCV) infection is associated with fatigue and depression. Cognitive impairments are also reported in a smaller number of HCV-positive patients. Recent studies linked HCV to low-grade inflammation in brain. Here, we test the hypothesis that chronic HCV is associated with 3T-neuroimaging-derived grey matter volume (GMV) and functional connectivity alterations in a sample of chronic HCV (1b), without severe liver disease. Regional GMV and resting-state fMRI-derived eigenvector centrality (EC) were compared between 19 HCV-positive patients and 23 healthy controls (all females, 50-69 and 52-64 years, respectively), controlling for white matter hyperintensities and age. Standard tests were used to assess fatigue, depression and cognitive performance. Also, liver fibrosis stage and viral load were quantified among patients. In comparison with controls, HCV-positive patients had higher scores in fatigue and depression, and worse alertness scores. The groups performed similarly in other cognitive domains. We report higher EC in a cluster in the right anterior superior parietal lobule in patients, while no differences are found in GMV. Post hoc functional connectivity analysis showed increased connectivity of this cluster with primary and secondary somatosensory cortex, and temporal and occipital lobes in patients. Higher mean EC in the superior parietal cluster, adjusted for mean framewise displacement, was associated with better memory and attention performance, but not with fatigue, depression, viral load or level of liver fibrosis, among patients. These results suggest a compensatory mechanism in chronic hepatitis C and explain equivocal results in the literature about cognitive deficits in infected persons. Further studies should define the relation of these connectivity changes to the brain's inflammatory activity.

Real-world experience with the all-oral, interferon-free regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir for the treatment of chronic hepatitis C virus infection in the German Hepatitis C Registry.

Real-world studies are relevant to complement clinical trials on novel antiviral therapies against chronic hepatitis C; however, clinical practice data are currently limited. This study investigated effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r)±dasabuvir (DSV)±ribavirin (RBV) for treatment of HCV genotype (GT) 1 and GT4 infection in a large real-world cohort. The German Hepatitis C Registry is an observational cohort study prospectively collecting clinical practice data on direct-acting antiviral therapies. Patients with GT1/4 infection treated with OBV/PTV/r±DSV±RBV were analysed. Effectiveness was assessed by sustained virologic response in 558 patients who reached post-treatment week 12 (SVR12). Safety is reported in 1017 patients who initiated treatment. Of the patients, 892 (88%) had GT1 and 125 (12%) had GT4 infection. Prior treatment experience and cirrhosis were reported in 598 (59%) and 228 (22%) patients, respectively. Overall, SVR12 (mITT) was 96% (486/505) in GT1- and 100% (53/53) in GT4 patients. SVR12 rates were high across subgroups including patients with cirrhosis (95%, 123/129), patients with moderate to severe renal impairment (100%, 34/34), and subgroups excluded from registrational trials like patients ≥70 years (96%, 64/67) and failures to prior protease inhibitor treatment (96%, 46/48). Adverse events (AEs) and serious AEs were reported in 52% (525/1017) and 2% (21/1017) of patients, respectively, and led to treatment discontinuation in 1.5% (15/1017) of patients. OBV/PTV/r±DSV±RBV was effective and generally well tolerated for treatment of HCV infection in clinical practice.

Characterization of buffy coat-derived granulocytes for clinical use: a comparison with granulocyte colony-stimulating factor/dexamethasone-pretreated donor-derived products.

BACKGROUND AND OBJECTIVES: Buffy coat-derived granulocytes have been described as an alternative to the apheresis product from donors pretreated with dexamethasone and granulocyte colony-stimulating factor (G-CSF). The latter is - dependent on the local and national settings - obtained following a demanding and time-consuming procedure, which is undesirable in critically ill septic patients. In contrast, buffy coat-derived products have a large volume and are often heavily contaminated with red cells and platelets. We developed a new pooled buffy coat-derived product with high purity and small volume, and performed a comprehensive functional characterization of these granulocytes. MATERIALS AND METHODS: We pooled ten buffy coats following the production of platelet concentrates. Saline 0·9% was added to decrease the viscosity and the product was split into plasma, red cells and a 'super' buffy coat. Functional data of the granulocytes were compared to those obtained with granulocytes from healthy controls and G-CSF/dexamethasone-pretreated donors. RESULTS: Buffy coat-derived granulocytes showed adhesion, chemotaxis, reactive oxygen species production, degranulation, NETosis and in vitro killing of Staphylococcus aureus, Escherichia coli and Aspergillus species comparable to control and G-CSF/dexamethasone-derived granulocytes. Candida killing was superior compared to G-CSF/dexamethasone-derived granulocytes. Immunophenotyping was normal; especially no signs of activation in the buffy coat-derived granulocytes were seen. Viability was reduced. Buffy coats are readily available in the regular blood production process and would take away the concerns around the apheresis product. CONCLUSION: The product described appears a promising alternative for transfusion purposes.

Bispectral Index Guided Target Controlled Midazolam Sedation: a new advanced technique for dental procedures.

Objectives: To assess the efficacy and safety of Bispectral Index (BIS) guided Target Controlled Infusion (TCI) of midazolam for anxiolysis or minimal sedation during extensive periodontal or implant surgery in a single operator/sedationist model. Methods: Retrospective analysis of thirty adult ASA 1 or ASA 2 patients undergoing periodontal surgery or dental implant surgery under local anaesthesia were included. The calculated effect site concentration (Ce) of midazolam applied by TCI, BIS, heart rate (HR), and peripheral oxygen saturation (SpO2) were monitored continuously. Non-invasive blood pressure (NIBP) and mean arterial pressure (MAP) were measured every 10 minutes. All peri-operative parameters were recorded every 10 minutes. All patients were interviewed 1 week after the procedure to explore their experience of sedation and the periodontal or implant surgery procedure. Results: Extensive periodontal or implant surgery treatment in all 30 patients was completed in a mean time of 120 min (range 50-180 min). The calculated mean effect site concentration for midazolam was 50 ng/ml (range 24-80). The mean BIS was 85 (74-100) during induction and was maintained between 80 and 90 during the oral surgical procedure by adjusting TCI Ce. There were no clinically significant cardiopulmonary changes during midazolam infusion with regard to SpO2, NIBP, MAP and heart rate. Patients experienced profound anterograde amnesia and were very satisfied with the sedation and the surgical procedure. Conclusions: BIS guided TCI sedation with midazolam facilitates predictable minimal sedation enabling long periodontal or implant surgery procedures by a single operator/sedationist within safe physiological limits.

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.

Hepatitis C viral dynamics during ribavirin priming differ according to prior treatment response and HCV type.

The mode of action of ribavirin is not completely understood. Ribavirin monotherapy has a measurable antiviral effect, which shows great variability. It might lead to an earlier steady state of plasma concentration and therefore enhance the effect of following combination treatment. The aim of this study was to evaluate the antiviral effect of ribavirin priming and its influence on sustained virologic response after combination treatment in a group of patients with different hepatitis C virus (HCV) types with or without prior treatment experience. Retrospective analysis of 75 patients (37 treatment naïve, 20 prior relapse, 16 prior nonresponse, genotype 1 present in 60 patients) from five centres who received ribavirin priming as part of an individual strategy in order to improve treatment outcome. All patients received ribavirin monotherapy with a mean dose of 14.5 mg kg-1 body weight for a mean of 28 days. After ribavirin priming, dual combination treatment with pegylated interferon alfa and ribavirin was started. The mean HCV RNA decline after ribavirin priming was 0.6 log10  IU mL-1 (P<.001). The initial viral decline depended on HCV type and previous treatment status being highest among prior relapsers (0.8 log10  IU mL-1 ; P=.002) and HCV type 2/3 (1.2 log10  IU mL-1 ; P=.05) and lowest among those with prior nonresponse (0.3 log10  IU mL-1 , P=.01). IFNL4 (formerly IL28B) genotype for rs12979860 and IFNL3 genotype rs8099917 did not influence the initial viral decline. The study demonstrates a significant variability in the viral dynamics and antiviral efficacy of ribavirin monotherapy, which is mainly influenced by prior treatment status. The fact that the lowest response pattern was observed in prior nonresponder patients to pegylated interferon alfa plus ribavirin combination therapy can be taken as a hint that not only the individual interferon, but also the ribavirin sensitivity contributes significantly to the nonresponsive state.

The national web-based outbreak rapid alert system in Norway: eight years of experience, 2006-2013.

In 2005, the Norwegian Institute of Public Health established a web-based outbreak rapid alert system called Vesuv. The system is used for mandatory outbreak alerts from municipal medical officers, healthcare institutions, and food safety authorities. As of 2013, 1426 outbreaks have been reported, involving 32913 cases. More than half of the outbreaks occurred in healthcare institutions (759 outbreaks, 53·2%). A total of 474 (33·2%) outbreaks were associated with food or drinking water. The web-based rapid alert system has proved to be a helpful tool by enhancing reporting and enabling rapid and efficient information sharing between different authorities at both the local and national levels. It is also an important tool for event-based reporting, as required by the International Health Regulations (IHR) 2005. Collecting information from all the outbreak alerts and reports in a national database is also useful for analysing trends, such as occurrence of certain microorganisms, places or sources of infection, or route of transmission. This can facilitate the identification of specific areas where more general preventive measures are needed.

HBsAg and anti-HCV screening in elderly hospitalized patients of a German tertiary referral centre.

BACKGROUND: Elderly patients are under-represented in hepatitis B and C screening approaches, but may be at increased risk for advanced liver disease. We therefore screened a hospitalized elderly population. MATERIALS AND METHODS: 6011 admissions to the department of internal medicine and neurology within one year were screened for HBsAg and anti-HCV (Elecsys(®)-HBsAg and -anti-HCV). Positive anti-HCV results were confirmed with the INNO-LIA™ assay. HCV-RNA was analyzed by real-time PCR in the case of confirmed positive anti-HCV results, HBV-DNA in the confirmed HBsAg positive individuals. RESULTS: Patient´s mean age (62.4 years) was 19 years above that of the average German population. The confirmed HBsAg prevalence was 0.6 %. 34 % (n = 12/35) of HBsAg positive cases were newly diagnosed, three of them presented with HBV-DNA levels > 2000 IU/mL. The confirmed anti-HCV prevalence was 0.9 %. 14 % (n = 8/56) of anti-HCV positive patients were previously undiagnosed. HCV-RNA was positive in three of them. In newly diagnosed individuals cirrhosis was present in 1/12 of the HBsAg and in 3/8 of the anti-HCV positive individuals. Compared to non-infected controls, the following risk factors were significantly more frequent in infected patients: (i) HBsAg: sexual exposure (20 % vs. 2 %), blood transfusion before 1992 (13 % vs. 6 %), referrals from nursing homes (10 % vs. 1 %). (ii) Anti-HCV: blood transfusion before 1992 (41 % vs. 6 %), IVDU (25 % vs. 0.5 %), organ transplantation (20 % vs. 5 %), hemodialysis (11 % vs. 3 %). CONCLUSIONS: HBsAg and anti-HCV were underdiagnosed in a senescent population, however, only few cases presented with advanced liver disease. Referrals from nursing homes were at increased risk for HBV infection.