Increased erythroferrone levels in malarial anaemia.

We assessed the diagnostic potential of erythroferrone as a biomarker for iron homeostasis comparing iron deficiency cases with anaemia of inflammation and controls. The dysregulation of the hepcidin axis was observed by Latour et al. in a mouse model of malarial anaemia induced by prolonged Plasmodium infection leading to increased erythroferrone concentrations. In line with that, we found significantly higher erythroferrone levels in cases with malaria and anaemia in an African population, compared to asymptomatic controls. Therefore, our findings extend the previous ones of the mouse model, suggesting also a dysregulation of the hepcidin axis in humans, which should be further corroborated in prospective studies and may lay the basis for the development of improved treatment strategies according to ERFE concentrations in such patients.

Exploring the host factors affecting asymptomatic Plasmodium falciparum infection: insights from a rural Burkina Faso study.

BACKGROUND: Asymptomatic Plasmodium falciparum parasitaemia forms a reservoir for the transmission of malaria disease in West Africa. Certain haemoglobin variants are known to protect against severe malaria infection. However, data on the potential roles of haemoglobin variants and nongenetic factors in asymptomatic malaria infection is scarce and controversial. Therefore, this study investigated the associations of iron homeostasis, inflammation, nutrition, and haemoglobin mutations with parasitaemia in an asymptomatic cohort from a P. falciparum-endemic region during the high transmission season. METHODS: A sub-study population of 688 asymptomatic individuals (predominantly children and adolescents under 15 years, n = 516) from rural Burkina Faso previously recruited by the NOVAC trial (NCT03176719) between June and October 2017 was analysed. Parasitaemia was quantified with conventional haemocytometry. The haemoglobin genotype was determined by reverse hybridization assays targeting a selection of 21 HBA and 22 HBB mutations. Demographics, inflammatory markers (interleukins 6 and 10, hepcidin), nutritional status (mid upper-arm circumference and body mass index), and anaemia (total haemoglobin, ferritin, soluble transferrin receptor) were assessed as potential predictors through logistic regression. RESULTS: Malaria parasites were detected in 56% of subjects. Parasitaemia was associated most strongly with malnutrition. The effect size increased with malnutrition severity (OR = 6.26, CI95: 2.45-19.4, p < 0.001). Furthermore, statistically significant associations (p < 0.05) with age, cytokines, hepcidin and heterozygous haemoglobin S were observed. CONCLUSIONS: According to these findings, asymptomatic parasitaemia is attenuated by haemoglobin S, but not by any of the other detected genotypes. Aside from evidence for slight iron imbalance, overall undernutrition was found to predict parasitaemia; thus, further investigations are required to elucidate causality and inform strategies for interventions.

Distinct smell and taste disorder phenotype of post-acute COVID-19 sequelae.

PURPOSE: Olfactory dysfunction (OD) commonly accompanies coronavirus disease 2019 (COVID-19). We investigated the kinetics of OD resolution following SARS-CoV-2 infection (wild-type and alpha variant) and its impact on quality of life, physical and mental health. METHODS: OD prevalence was assessed in an ambulatory COVID-19 survey (n = 906, ≥ 90 days follow-up) and an observational cohort of ambulatory and hospitalized individuals (n = 108, 360 days follow-up). Co-occurrence of OD with other symptoms and effects on quality of life, physical and mental health were analyzed by multi-dimensional scaling, association rule mining and semi-supervised clustering. RESULTS: Both in the ambulatory COVID-19 survey study (72%) and the observational ambulatory and hospitalized cohort (41%) self-reported OD was frequent during acute COVID-19. Recovery from self-reported OD was slow (survey: median 28 days, observational cohort: 90 days). By clustering of the survey data, we identified a predominantly young, female, comorbidity-free group of convalescents with persistent OD and taste disorders (median recovery: 90 days) but low frequency of post-acute fatigue, respiratory or neurocognitive symptoms. This smell and taste disorder cluster was characterized by a high rating of physical performance, mental health, and quality of life as compared with convalescents affected by prolonged fatigue or neurocognitive complaints. CONCLUSION: Our results underline the heterogeneity of post-acute COVID-19 sequelae calling for tailored management strategies. The persistent smell and taste disorder phenotype is characterized by good clinical, physical, and mental recovery and may pose a minor challenge for public health. STUDY REGISTRATION: ClinicalTrials.gov: NCT04661462 (survey study), NCT04416100 (observational cohort).

Phenotyping of Acute and Persistent Coronavirus Disease 2019 Features in the Outpatient Setting: Exploratory Analysis of an International Cross-sectional Online Survey.

BACKGROUND: Long COVID, defined as the presence of coronavirus disease 2019 (COVID-19) symptoms ≥28 days after clinical onset, is an emerging challenge to healthcare systems. The objective of the current study was to explore recovery phenotypes in nonhospitalized individuals with COVID-19. METHODS: A dual cohort, online survey study was conducted between September 2020 and July 2021 in the neighboring European regions Tyrol (TY; Austria, n = 1157) and South Tyrol (STY; Italy, n = 893). Data were collected on demographics, comorbid conditions, COVID-19 symptoms, and recovery in adult outpatients. Phenotypes of acute COVID-19, postacute sequelae, and risk of protracted recovery were explored using semi-supervised clustering and multiparameter least absolute shrinkage and selection operator (LASSO) modeling. RESULTS: Participants in the study cohorts were predominantly working age (median age [interquartile range], 43 [31-53] years] for TY and 45 [35-55] years] for STY) and female (65.1% in TY and 68.3% in STY). Nearly half (47.6% in TY and 49.3% in STY) reported symptom persistence beyond 28 days. Two acute COVID-19 phenotypes were discerned: the nonspecific infection phenotype and the multiorgan phenotype (MOP). Acute MOP symptoms encompassing multiple neurological, cardiopulmonary, gastrointestinal, and dermatological symptoms were linked to elevated risk of protracted recovery. The major subset of individuals with long COVID (49.3% in TY; 55.6% in STY) displayed no persistent hyposmia or hypogeusia but high counts of postacute MOP symptoms and poor self-reported physical recovery. CONCLUSIONS: The results of our 2-cohort analysis delineated phenotypic diversity of acute and postacute COVID-19 manifestations in home-isolated patients, which must be considered in predicting protracted convalescence and allocating medical resources.

Wastewater surveillance of SARS-CoV-2 in Austria: development, implementation, and operation of the Tyrolean wastewater monitoring program.

Wastewater-based epidemiology (WBE) is an effective approach for tracking information on spatial distribution and temporal trends of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the community level. Herein, the development, implementation, and operation of the wastewater monitoring program serving Tyrol - a federal province of Austria - are described. The development of this program was initiated by Tyrolean health authorities at the end of the first phase of the Coronavirus disease 2019 (COVID-19) pandemic (May 2020). In close co-operation with the water sector and academic institutions, efficient and effective workflows and processes for wastewater surveillance were established. The monitoring program went into operation in November 2020. By the end of July 2021, a total of 5,270 wastewater influent samples collected at 43 sites were analyzed. The monitoring program provided valuable insights into the development of the pandemic situation in Tyrol and fulfilled several tasks that are of importance in different phases of the pandemic. It represented an early-warning system, provided independent confirmation of temporal trends in COVID-19 prevalence, enabled the assessment of the effectiveness of measures, alerted about bursts of disease activity, and provided evidence for the absence of COVID-19. These findings underline the importance of establishing national wastewater monitoring programs as a complementary source of information for efficient and effective pandemic management.

[Attitudes toward persons with dementia : A population survey from Switzerland]. / Einstellungen gegenüber Menschen mit Demenz : Eine Bevölkerungsbefragung aus der Schweiz.

BACKGROUND: Dementia diseases, primarily Alzheimer's disease, are on the rise worldwide. Adequate management of this development requires the involvement of the general population in appropriate measures; it also requires knowledge of the attitudes of the population with respect to the disease and the people it affects. A survey was thus conducted to discover the Swiss population's attitude towards people with Alzheimer's disease or related forms of dementia (ADRD) and identify the factors that influence this attitude. MATERIAL AND METHODS: A nationwide standardized telephone survey of 862 people aged 18 years and older was conducted in German, French, and Italian between July and September 2018. RESULTS: Age and attitude toward age were found to be significant predictors of attitudes towards people with ADRD. Subdividing this attitude into a cognitive and an affective conative component helped to more precisely assign the influences of independent variables. Regression models showed a positive effect on the affective conative component for contact with people with ADRD, being well informed, experienced pleasures, and a positive attitude toward age, while education, gender, and age had a positive impact on the cognitive component. Nevertheless, the independent variables could explain only part of the variance. CONCLUSION: Despite the overall positive attitude toward people with ADRD in the Swiss population, the results of this study have certain practical implications: in addition to being well informed, experience with people with ADRD has a positive influence on attitudes toward persons with this disease. Therefore, such contact should be encouraged to revise any negative perceptions of people with ADRD.

FTIR Nanospectroscopy Shows Molecular Structures of Plant Biominerals and Cell Walls.

Plant tissues are complex composite structures of organic and inorganic components whose function relies on molecular heterogeneity at the nanometer scale. Scattering-type near-field optical microscopy (s-SNOM) in the mid-infrared (IR) region is used here to collect IR nanospectra from both fixed and native plant samples. We compared structures of chemically extracted silica bodies (phytoliths) to silicified and nonsilicified cell walls prepared as a flat block of epoxy-embedded awns of wheat (Triticum turgidum), thin sections of native epidermis cells from sorghum (Sorghum bicolor) comprising silica phytoliths, and isolated cells from awns of oats (Avena sterilis). The correlation of the scanning-probe IR images and the mechanical phase image enables a combined probing of mechanical material properties together with the chemical composition and structure of both the cell walls and the phytolith structures. The data reveal a structural heterogeneity of the different silica bodies in situ, as well as different compositions and crystallinities of cell wall components. In conclusion, IR nanospectroscopy is suggested as an ideal tool for studies of native plant materials of varied origins and preparations and could be applied to other inorganic-organic hybrid materials.

Hyperspectral time-domain terahertz nano-imaging.

Terahertz (THz) near-field microscopy has wide and unprecedented application potential for nanoscale materials and photonic-device characterization. Here, we introduce hyperspectral THz nano-imaging by combining scattering-type scanning near-field optical microscopy (s-SNOM) with THz time-domain spectroscopy (TDS). We describe the technical implementations that enabled this achievement and demonstrate its performance with a heterogeneously doped Si semiconductor sample. Specifically, we recorded a hyperspectral image of 40 by 20 pixels in 180 minutes and with a spatial resolution of about ~170 nm by measuring at each pixel with a time domain spectrum covering the range from 0.4 to 1.8 THz. Fitting the spectra with a Drude model allows for measuring-noninvasively and without the need for Ohmic contacts-the local mobile carrier concentration of the differently doped Si areas. We envision wide application potential for THz hyperspectral nano-imaging, including nanoscale carrier profiling of industrial semiconductor structures or characterizing complex and correlated electron matter, as well as low dimensional (1D or 2D) materials.

Association of serum sphingomyelin profile with clinical outcomes in patients with lower respiratory tract infections: results of an observational, prospective 6-year follow-up study.

Background Sphingolipids - the structural cell membrane components - and their metabolites are involved in signal transduction and participate in the regulation of immunity. We investigated the prognostic implications of sphingolipid metabolic profiling on mortality in a large cohort of patients with lower respiratory tract infections (LRTIs). Methods We measured 15 different sphingomyelin (SM) types in patients with LRTIs from a previous Swiss multicenter trial that examined the impact of procalcitonin-guided antibiotic therapy on total antibiotic use and rates and duration of hospitalization. Primary and secondary end points were adverse outcomes - defined as death or intensive care unit admission within 30 days - and 6-year mortality. Results Of 360 patients, 8.9% experienced an adverse outcome within 30 days and 46% died within 6 years. Levels of all SM types were significantly lower in pneumonia patients vs. those with chronic obstructive pulmonary disease (COPD) exacerbation (p<0.0001 for all comparisons). Sphingomyelin subspecies SM (OH) C22:1 and SM (OH) C22:2 were associated with lower risk for short-term adverse outcomes (sex-, gender- and comorbidity-adjusted odds ratios [OR]: 0.036; 95% confidence interval [CI], 0.002-0.600; p=0.021 and 0.037; 95% CI, 0.001-0.848; p=0.039, respectively). We found no significant associations with 6-year mortality for any SM. Conclusions Circulating sphingolipid levels are lower in inflammatory conditions such as pneumonia and correlate with adverse short-term outcomes. Further characterization of the physiological, pathophysiological and metabolic roles of sphingolipids under inflammatory conditions may facilitate understanding of their roles in infectious disease.

Comparison of Five TSH-Receptor Antibody Assays in Graves' disease: results from an observational pilot study.

BACKGROUND: Early diagnosis and relapse prediction in Graves' disease influences treatment. We assessed the abilities of four TSH-receptor antibody tests [TRAb] and one cyclic adenosine monophosphate bioassay to predict relapse of Graves' disease. METHODS: Observational study investigating patients presenting with Graves' disease at a Swiss hospital endocrine referral center or an endocrine outpatient clinic. Main outcomes were diagnosis and relapse of Graves' disease after stop of anti-thyroid drugs. We used Cox regression to study associations of TRAb levels with relapse risk and calculated c-statistics [AUC] to assess discrimination. Blood draws took place as close as possible to treatment initiation. RESULTS: AUCs ranged from 0.90 (TSAb Biossay by RSR) to 0.97 (IMMULITE TSI by Siemens). Highest sensitivity (94.0%) was observed for IMMULITE TSI and RSR TRAb Fast, while the greatest specificity (97.9%) was found with the EliA anti-TSH-R (by Thermo Fisher). In Cox regression analysis comparing the highest versus the lower quartiles, the highest hazard ratio [HR] for relapse was found for BRAHMS TRAK (by Thermo Fisher) (2.98, 95% CI 1.13-7.84), IMMULITE TSI (2.40, 95% CI 0.91-6.35), EliA anti-TSH-R (2.05, 95% CI 0.82-5.10), RSR Fast TRAb (1.80, 95% CI 0.73-4.43), followed by RSR STIMULATION (1.18, 95% CI 0.46-2.99). Discrimination analyses showed respective AUCs of 0.68, 0.65, 0.64, 0.64, and 0.59. CONCLUSION: The assays tested had good diagnostic power and relapse risk prediction with few differences among the new assays. Due to the small sample size and retrospective design with possible selection bias, our data need prospective validation.

Dihydrotestosterone is a predictor for mortality in males with community-acquired pneumonia: results of a 6-year follow-up study.

BACKGROUND: Adrenal hormone metabolite levels are altered in acute illnesses such as community-acquired pneumonia (CAP). Our aim was to investigate associations of sex and mineralocorticoid hormone metabolites with short- and long-term mortality and severity of CAP in male and female patients. METHODS: We prospectively followed 285 patients (60.4% male, mean age 71 years) with CAP from a previous multicenter trial. At baseline, levels of different metabolites of sex hormones and mineralocorticoids were measured by liquid chromatography coupled to tandem mass spectrometry. We calculated Cox regression models adjusted for age and comorbidities. RESULTS: All-cause mortality was 5.3% after 30 days and increased to 47.4% after 6 years. In males, high levels of dihydrotestosterone were associated with higher 6-year mortality (adjusted HR 2.84, 95%CI 1.15-6.99, p = 0.023), whereas high levels of 17-OH-progesterone were associated with lower 6-year mortality (adjusted HR 0.72, 95%CI 0.54-0.97, p = 0.029). Testosterone levels in males correlated inversely with inflammatory markers (CRP rho = - 0.39, p < 0.001; PCT rho = - 0.34, p < 0.001) and disease severity as assessed by the Pneumonia severity index (PSI) (rho = - 0.23, p = 0.003). No similar association was found for female patients. CONCLUSION: Whereas in males with CAP, sex and mineralocorticoid hormone metabolite levels correlated with inflammation, disease severity and long-term survival, no similar association was found for females. Further study of sex and mineralocorticoid hormones in acute illness could generate predictive signatures with implementation in clinical practice.

Association of the Tyrosine/Nitrotyrosine pathway with death or ICU admission within 30 days for patients with community acquired pneumonia.

BACKGROUND: Oxidative stress is a modifiable risk-factor in infection causing damage to human cells. As an adaptive response, cells catabolize Tyrosine to 3-Nitrotyrosine (Tyr-NO2) by nitrosylation. We investigated whether a more efficient reduction in oxidative stress, mirrored by a lowering of Tyrosine, and an increase in Tyr-NO2 and the Tyrosine/Tyr-NO2 ratio was associated with better clinical outcomes in patients with community-acquired pneumonia (CAP). METHODS: We measured Tyrosine and Tyr-NO2 in CAP patients from a previous randomized Swiss multicenter trial. The primary endpoint was adverse outcome defined as death or ICU admission within 30-days; the secondary endpoint was 6-year mortality. RESULTS: Of 278 included CAP patients, 10.4% experienced an adverse outcome within 30 days and 45.0% died within 6 years. After adjusting for the pneumonia Severity Index [PSI], BMI and comorbidities, Tyrosine nitrosylation was associated with a lower risk for short-term adverse outcome and an adjusted OR of 0.44 (95% CI 0.20 to 0.96, p = 0.039) for Tyr-NO2 and 0.98 (95% CI 0.98 to 0.99, p = 0.043) for the Tyrosine/Tyr-NO2 ratio. There were no significant associations for long-term mortality over six-years for Tyr-NO2 levels (adjusted hazard ratio 0.81, 95% CI 0.60 to 1.11, p = 0.181) and Tyrosine/Tyr-NO2 ratio (adjusted hazard ratio 1.00, 95% CI 0.99 to 1.00, p = 0.216). CONCLUSIONS: Tyrosine nitrosylation in our cohort was associated with better clinical outcomes of CAP patients at short-term, but not at long term. Whether therapeutic modulation of the Tyrosine/Tyr-NO2 pathway has beneficial effects should be evaluated in future studies. TRIAL REGISTRATION: ISRCTN95122877. Registered 31 July 2006.

Association of adrenal hormone metabolites and mortality over a 6-year follow-up in COPD patients with acute exacerbation.

BACKGROUND: The release of hormones from the adrenal gland is vital in acute and chronic illnesses such as chronic obstructive pulmonary disease (COPD) involving recurrent exacerbations. Using a metabolomic approach, we aim to investigate associations of different adrenal hormone metabolites with short- and long-term mortality in COPD patients. METHODS: We prospectively followed 172 COPD patients (median age 75 years, 62% male) from a previous Swiss multicenter trial. At baseline, we measured levels of a comprehensive spectrum of adrenal hormone metabolites, including glucocorticoid, mineralocorticoid and androgen hormones by liquid chromatography coupled with tandem mass spectrometry (MS). We calculated Cox regression models adjusted for gender, age, comorbidities and previous corticosteroid therapy. RESULTS: Mortality was 6.4% after 30 days and increased to 61.6% after 6 years. Higher initial androgen hormones predicted lower long-term mortality with significant results for dehydroepiandrosterone (DHEA) [adjusted hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.70-0.98; p=0.026] and dehydroepiandrosterone sulfate (DHEA-S) (adjusted HR, 0.68; 95% CI, 0.50-0.91; p=0.009). An activation of stress hormones (particularly cortisol and cortisone) showed a time-dependent effect with higher levels pointing towards higher mortality at short term, but lower mortality at long term. Activation of the mineralocorticoid axis tended to be associated with increased short-term mortality (adjusted HR of aldosterone, 2.76; 95% CI, 0.79-9.65; p=0.111). CONCLUSIONS: Independent of age, gender, corticosteroid exposure and exacerbation type, adrenal hormones are associated with mortality at short and long term in patients with COPD exacerbation with different time-dependent effects of glucocorticoids, androgens and mineralocorticoids. A better physiopathological understanding of the causality of these effects may have therapeutic implications.

Copeptin levels and commonly used laboratory parameters in hospitalised patients with severe hypernatraemia - the "Co-MED study".

BACKGROUND: Hypernatraemia is common in inpatients and is associated with substantial morbidity. Its differential diagnosis is challenging, and delayed treatment may have devastating consequences. The most important hormone for the regulation of water homeostasis is arginine vasopressin, and copeptin, the C-terminal portion of the precursor peptide of arginine vasopressin, might be a reliable new parameter with which to assess the underlying cause of hypernatraemia. METHODS: In this prospective, multicentre, observational study conducted in two tertiary referral centres in Switzerland, 92 patients with severe hyperosmolar hypernatraemia (Na+ > 155 mmol/L) were included. After a standardised diagnostic evaluation, the underlying cause of hypernatraemia was identified and copeptin levels were measured. RESULTS: The most common aetiology of hypernatraemia was dehydration (DH) (n = 65 [71%]), followed by salt overload (SO) (n = 20 [22%]), central diabetes insipidus (CDI) (n = 5 [5%]) and nephrogenic diabetes insipidus (NDI) (n = 2 [2%]). Low urine osmolality was indicative for patients with CDI and NDI (P < 0.01). Patients with CDI had lower copeptin levels than patients with DH or SO (both P < 0.01) or those with NDI. Copeptin identified CDI with an AUC of 0.99 (95% CI 0.97-1.00), and a cut-off value ≤ 4.4pmol/L showed a sensitivity of 100% and a specificity of 99% to predict CDI. Similarly, urea values were lower in CDI than in DH or SO (P < 0.05 and P < 0.01, respectively) or NDI. The AUC for diagnosing CDI was 0.98 (95% CI 0.96-1.00), and a cut-off value < 5.05 mmol/L showed high specificity and sensitivity for the diagnosis of CDI (98% and 100%, respectively). Copeptin and urea could not differentiate hypernatraemia induced by DH from that induced by SO (P = 0.66 and P = 0.30, respectively). CONCLUSIONS: Copeptin and urea reliably identify patients with CDI and are therefore helpful tools for therapeutic management in patients with severe hypernatraemia. TRIALS REGISTRATION: ClinicalTrials.gov, NCT01456533 . Registered on 20 October 2011.

Prediction of post-acute care demand in medical and neurological inpatients: diagnostic assessment of the post-acute discharge score - a prospective cohort study.

BACKGROUND: Early identification of patients requiring transfer to post-acute care (PAC) facilities shortens hospital stays. With a focus on interprofessional assessment of biopsychosocial risk, this study's aim was to assess medical and neurological patients' post-acute care discharge (PACD) scores on days 1 and 3 after hospital admission regarding diagnostic accuracy and effectiveness as an early screening tool. The transfer to PAC facilities served as the outcome ("gold standard"). METHODS: In this prospective cohort study, registered at ClinicalTrial.gov (NCT01768494) on January 2013, 1432 medical and 464 neurological patients (total n = 1896) were included consecutively between February and October 2013. PACD scores and other relevant data were extracted from electronic records of patient admissions, hospital stays, and interviews at day 30 post-hospital admission. To gauge the scores' accuracy, we plotted receiver operating characteristic (ROC) curves, calculated area under the curve (AUC), and determined sensitivity and specificity at various cut-off levels. RESULTS: Medical patients' day 1 and day 3 PACD scores accurately predicted discharge to PAC facilities, with respective discriminating powers (AUC) of 0.77 and 0.82. With a PACD cut-off of ≥8 points, day 1 and 3 sensitivities were respectively 72.6% and 83.6%, with respective specificities of 66.5% and 70.0%. Neurological patients' scores showed lower accuracy both days: using the same cut-off, respective day 1 and day 3 AUCs were 0.68 and 0.78, sensitivities 41.4% and 68.7% and specificities 81.4% and 83.4%. CONCLUSION: PACD scores at days 1 and 3 accurately predicted transfer to PAC facilities, especially in medical patients on day 3. To confirm and refine these results, PACD scores' value to guide discharge planning interventions and subsequent impact on hospital stay warrants further investigation. TRIAL REGISTRATION: ClinialTrials.gov Identifier, NCT01768494 .

Evaluation of copeptin and commonly used laboratory parameters for the differential diagnosis of profound hyponatraemia in hospitalized patients: 'The Co-MED Study'.

OBJECTIVE: Hyponatraemia is common and its differential diagnosis is challenging. Commonly used diagnostic algorithms have limited diagnostic accuracy. Copeptin, the c-terminal portion of the precursor peptide of arginine vasopressin might help in the differential diagnosis of hyponatraemia. DESIGN: Prospective multicentre observational study. PATIENTS/METHODS: A total of 298 patients admitted with profound hypoosmolar hyponatraemia (Na < 125 mmol/l) were evaluated. Three experts uninvolved in the patients' care determined the aetiology of hyponatraemia after standardized diagnostic evaluation. RESULTS: Hyponatraemia differential diagnoses were as follows: syndrome of inappropriate antidiuresis (SIAD), 106 patients (35·6%); 'diuretic-induced', 72 (24·2%); 'hypovolaemic', 59 (19·8%); 'hypervolaemic', 33 (11·1%); primary polydipsia (PP), 24 (8·1%); and cortisol deficiency, 4 (1·3%). Copeptin levels <3·9 pmol/l identified patients with PP with high specificity (91%). Further, copeptin levels >84 pmol/l were highly predictive for hypovolaemic hyponatraemia (specificity: 90%). Urinary sodium levels and copeptin/urinary sodium ratio in patients with SIAD were higher and lower as compared to other hyponatraemia aetiologies (P < 0·0001). However, the specificity to identify SIAD was moderate for both parameters (31% and 61%). Fractional uric acid excretion (FEUA ) and fractional urea excretion (FEurea ) were higher in patients with SIAD compared to other hyponatraemia aetiologies (both P < 0·0001). FEurea values >55% and FEUA values >12% had a specificity of 96% and 77% to detect patients with SIAD. These results remained similar after excluding patients taking diuretics. CONCLUSIONS: Overall, there is only limited diagnostic utility of copeptin in the differential diagnosis of profound hyponatraemia. Very low copeptin levels are seen in patients with PP and highest copeptin levels in hypovolaemic hyponatraemia. To discriminate between SIAD and other hyponatraemia aetiologies, FEurea and FEUA levels are valuable irrespective of diuretics use.

Admission levels of asymmetric and symmetric dimethylarginine predict long-term outcome in patients with community-acquired pneumonia.

BACKGROUND: During infection, there is an activation of the L-arginine-nitric-oxide pathway, with a shift from nitric oxide synthesis to a degradation of L-arginine to its metabolites, asymmetric and symmetric dimethylarginine (ADMA and SDMA). However, the prognostic implications for short-term or long-term survival remains unclear. We investigated the association of L-arginine, ADMA, and SDMA with adverse clinical outcomes in a well-defined cohort of patients with community-acquired pneumonia (CAP). METHODS: We measured L-arginine, ADMA, and SDMA in 268 CAP patients from a Swiss multicenter trial by mass spectrometry and used Cox regression models to investigate associations between blood marker levels and disease severity as well as mortality over a period of 6 years. RESULTS: Six-year mortality was 44.8%. Admission levels of ADMA and SDMA (µmol/L) were correlated with CAP severity as assessed by the pneumonia severity index (r = 0.32, p < 0.001 and r = 0.56, p < 0.001 for ADMA and SDMA, respectively) and higher in 6-year non-survivors versus survivors (median 0.62 vs. 0.48; p < 0.001 and 1.01 vs. 0.85; p < 0.001 for ADMA and SDMA, respectively). Both ADMA and SDMA were significantly associated with long-term mortality (hazard ratios [HR] 4.44 [95% confidence intervals (CI) 1.84 to 10.74] and 2.81 [95% CI 1.45 to 5.48], respectively). The effects were no longer significant after multivariate adjustment for age and comorbidities. No association of L-arginine with severity and outcome was found. CONCLUSIONS: Both ADMA and SDMA show a severity-dependent increase in patients with CAP and are strongly associated with mortality. This association is mainly explained by age and comorbidities. TRIAL REGISTRATION: ISRCTN95122877 . Registered 31 July 2006.