Nutritional support during the hospital stay reduces mortality in patients with different types of cancers: secondary analysis of a prospective randomized trial.

BACKGROUND: Nutritional support in patients with cancer aims at improving quality of life. Whether use of nutritional support is also effective in improving clinical outcomes requires further study. PATIENTS AND METHODS: In this preplanned secondary analysis of patients with cancer included in a prospective, randomized-controlled, Swiss, multicenter trial (EFFORT), we compared protocol-guided individualized nutritional support (intervention group) to standard hospital food (control group) regarding mortality at 30-day (primary endpoint) and other clinical outcomes. RESULTS: We analyzed 506 patients with a main admission diagnosis of cancer, including lung cancer (n = 113), gastrointestinal tumors (n = 84), hematological malignancies (n = 108) and other types of cancer (n = 201). Nutritional risk based on Nutritional Risk Screening (NRS 2002) was an independent predictor for mortality over 180 days with an (age-, sex-, center-, type of cancer-, tumor activity- and treatment-) adjusted hazard ratio of 1.29 (95% CI 1.09-1.54; P = 0.004) per point increase in NRS. In the 30-day follow-up period, 50 patients (19.9%) died in the control group compared to 36 (14.1%) in the intervention group resulting in an adjusted odds ratio of 0.57 (95% CI 0.35-0.94; P = 0.027). Interaction tests did not show significant differences in mortality across the cancer type subgroups. Nutritional support also significantly improved functional outcomes and quality of life measures. CONCLUSIONS: Compared to usual hospital nutrition without nutrition support, individualized nutritional support reduced the risk of mortality and improved functional and quality of life outcomes in cancer patients with increased nutritional risk. These data further support the inclusion of nutritional care in cancer management guidelines.

Cytokines and Cortisol - predictors of treatment response to corticosteroids in community-acquired pneumonia?

BACKGROUND: A previous study found community-acquired pneumonia (CAP) patients with imbalance of high inflammation and discordantly low cortisol levels to benefit most from adjunctive corticosteroid treatment. Our aim was to validate this hypothesis in a preplanned secondary analysis of the randomized controlled STEP trial. METHODS: Patients included in the STEP trial receiving 50 mg prednisone or placebo for 5 days were categorized based on pro-inflammatory cytokines (Interleukin-6/8/MCP-1), CRP and cortisol levels on admission into four groups (high/low inflammation and high/low cortisol). The primary combined end-point was mortality or ICU admission within 30 days. RESULTS: In total, 632 patients (315 prednisone, 317 placebo) were included in this analysis. Prednisone did not significantly reduce the risk for the primary end-point in patients with high cytokines/low cortisol and in any other subgroups. However, we noted some differences in the strength of corticosteroid effect in the different subgroups with stronger effects in patients with high cytokines [OR 0.44 (0.10,1.72)] compared to patients with low cytokines [OR 0.68 (0.30,1.5)] (P-interaction = 0.600). The effects did not differ according to cortisol levels. CONCLUSION: The imbalance of high inflammation state and low cortisol levels did not predict treatment response to corticosteroids in patients with CAP. However, in line to previous research, inflammation as measured by cytokine levels irrespective of cortisol tended to predict treatment response to corticosteroids in CAP. Whether this concept may help to personalize corticosteroids to patients most likely benefitting from this treatment needs to be tested in future intervention trials.

Hyponatremia and activation of vasopressin secretion are both independently associated with 30-day mortality: results of a multicenter, observational study.

BACKGROUND: Hyponatremia is a common feature of acute illness and associated with increased mortality. This may be explained by a stress-mediated activation of the vasopressin system with an increase in free-water reabsorption. OBJECTIVES: To investigate whether the association between hyponatremia and mortality could be explained by activation of the vasopressin system. METHODS: We prospectively enrolled adult, medical patients seeking emergency care in three centres in Switzerland, France and the United States. We investigated associations between admission plasma sodium and copeptin, a stable portion of the vasopressin-precursor peptide, with 30-day mortality. We performed uni- and multivariate regression analysis. RESULTS: Of 6962 included patients, 18% had hyponatremia (sodium ≤135 mmol L-1 ), which doubled their risk for mortality compared to patients with normonatremia (8.3% vs. 3.8%). This association was confirmed in a multivariate-adjusted logistic regression analysis [adjusted odds ratio (OR) 1.47, 95% CI 1.12-1.93, P = 0.005]. Vasopressin levels, mirrored by copeptin, were also increased in nonsurvivors and strongly associated with mortality (adjusted OR 3.42, 95% CI 2.76-4.25, P < 0.001). The association between hyponatremia and mortality remained unchanged when adding copeptin levels to the regression model (fully adjusted OR 1.53, 95% CI 1.16-2.00, P = 0.002). CONCLUSION: This prospective study including medical patients upon emergency room admission found hyponatremia as well as an activation of the vasopressin system to be independently associated with mortality. This suggests that stress- and vasopressin-independent mechanisms are responsible for the association of low sodium levels with mortality.

The association of admission hyperglycaemia and adverse clinical outcome in medical emergencies: the multinational, prospective, observational TRIAGE study.

AIMS: The clinical relevance of hyperglycaemia in an emergency department population remains incompletely understood. We investigated the association between admission blood glucose levels and adverse clinical outcomes in a large emergency department cohort. METHODS: We prospectively enrolled 7132 adult medical patients seeking emergency department care in three tertiary care hospitals in Switzerland, France and the USA. We used adjusted multivariable logistic regression models to examine the association between admission blood glucose levels and 30-day mortality, as well as adverse clinical course stratified by pre-existing diabetes and principal medical diagnoses. RESULTS: In 6044 people without diabetes (84.7%), severe hyperglycaemia, defined as a glucose level of > 11.1 mmol/l (200 mg/dl), was associated with a doubling in the risk of 30-day mortality [adjusted odds ratio (OR) 1.9; 95% confidence interval (95% CI), 1.1 to 3.3; P = 0.018] and a three-fold increase in the risk of intensive care unit admission (adjusted OR 3.0; 95% CI, 1.9 to 4.9; P < 0.001). These associations were similar among different diagnoses. In the population with diabetes (n = 1088), no association with 30-day mortality was found (adjusted OR 1.0; 95% CI, 0.6 to 1.8; P for interaction = 0.001), whereas the association with intensive care unit admission was weaker (adjusted OR 2.4; 95% CI, 1.5 to 4.1; P for interaction = 0.011). Overall 30-day mortality was higher in those with diabetes than in those without (6.1 vs. 4.4%, P = 0.015). CONCLUSIONS: In this large medical emergency department patient cohort, admission hyperglycaemia was strongly associated with adverse clinical course in people without diabetes. (Clinical Trial Registry No: NCT01768494).

Clinical risk scores and blood biomarkers as predictors of long-term outcome in patients with community-acquired pneumonia: a 6-year prospective follow-up study.

OBJECTIVE: Prediction of long-term outcomes in patients with community-acquired pneumonia (CAP) is incompletely understood. We investigated the value of clinical risk scores [pneumonia severity index (PSI) and CURB-65] (Confusion, Urea, Respiratory rate, Blood Pressure, Age >65 years) and blood biomarkers of different physiopathological pathways in predicting long-term survival in a well-characterized cohort of patients with CAP enrolled in an antibiotic stewardship trial. DESIGN, SETTING AND SUBJECTS: Patients admitted with CAP to six medical centres in Switzerland were prospectively followed for 6 years. Cox regression models and area under the receiver operating characteristics curve (AUC) were used to investigate associations between initial risk assessment and all-cause mortality. MAIN OUTCOME MEASURE: All-cause mortality during a 6-year follow-up period. RESULTS: Six-year mortality in the present cohort (median age 73 years) was 45.1% [95% confidence interval (CI) 41.8-48.3%]. Initial PSI and CURB-65 scores both had excellent long-term prognostic accuracy, with a stepwise increase in mortality per risk class. The hazard ratios (95% CI) of the highest PSI and CURB-65 classes (reference: lowest class) were 38.0 (14.0-103.0) and 7.8 (2.2-14.5), respectively, after 6 years. The addition of inflammatory (pro-adrenomedullin) and cardiac (pro-atrial natriuretic peptide) blood biomarkers measured upon hospital admission further improved the prognostic capabilities of the PSI (AUC increase from 0.79 to 0.83; P < 0.0001) and the CURB-65 score (AUC increase from 0.73 to 0.80; P < 0.001). CONCLUSION: Risk assessment using clinical scores allowed accurate long-term prognostication, which was further improved by the addition of two inflammatory (pro-adrenomedullin) and cardiac (pro-atrial natriuretic peptide) blood biomarkers. These data provide a rationale for a more risk-adapted, 'personalized' strategy for long-term management of patients with CAP.

Mid-regional pro-atrial natriuretic peptide and the assessment of volaemic status and differential diagnosis of profound hyponatraemia.

BACKGROUND: Hyponatraemia is common and its differential diagnosis and consequent therapy management is challenging. The differential diagnosis is mainly based on the routine clinical assessment of volume status, which is often misleading. Mid-regional pro-atrial natriuretic peptide (MR-proANP) is associated with extracellular and cardiac fluid volume. METHODS: A total of 227 consecutive patients admitted to the emergency department with profound hypo-osmolar hyponatraemia (Na < 125 mmol L(-1) ) were included in this prospective multicentre observational study conducted in two tertiary centres in Switzerland. A standardized diagnostic evaluation of the underlying cause of hyponatraemia was performed, and an expert panel carefully evaluated volaemic status using clinical criteria. MR-proANP levels were compared between patients with hyponatraemia of different aetiologies and for assessment of volume status. RESULTS: MR-proANP levels were higher in patients with hypervolaemic hyponatraemia compared to patients with hypovolaemic or euvolaemic hyponatraemia (P = 0.0002). The area under the curve (AUC) to predict an excess of extracellular fluid volume, compared to euvolaemia, was 0.73 [95% confidence interval (CI) 0.62-0.84]. Additionally, in multivariate analysis, MR-proANP remained an independent predictor of excess extracellular fluid volume after adjustment for congestive heart failure (P = 0.012). MR-proANP predicted the syndrome of inappropriate antidiuresis (SIAD) versus hypovolaemic and hypervolaemic hyponatraemia with an AUC of 0.77 (95% CI 0.69-0.84). CONCLUSION: MR-proANP is associated with extracellular fluid volume in patients with hyponatraemia and remains an independent predictor of hypervolaemia after adjustment for congestive heart failure. MR-proANP may be a marker for discrimination between the SIAD and hypovolaemic or hypervolaemic hyponatraemia.

Muscle matters: Prognostic implications of malnutrition and muscle health parameters in patients with cancer. A secondary analysis of a randomised trial.

BACKGROUND: Low muscle mass and malnutrition are independently associated with an increased risk of adverse outcomes in patients with cancer. However, it is not yet clear which parameter is most indicative of these risks. This study investigates the prognostic significance of different parameters reflecting malnutrition and muscle health in a well-characterised oncology population at nutritional risk. METHODS: This preplanned secondary analysis included patients with cancer from a Swiss-wide, randomised-controlled nutritional trial. We investigated associations among malnutrition markers (i.e., malnutrition diagnosis based on modified Global Leadership Initiative on Malnutrition (GLIM) criteria, albumin concentration) and muscle health markers (i.e., hand grip strength, computed tomography (CT)-based muscle mass and radiodensity) with 180-day all-cause mortality (primary outcome). RESULTS: We included 269 patients with a main admission diagnosis of cancer and available CT scans. In a mutually adjusted model, four parameters contributed to risk assessment including modified malnutrition diagnosis (GLIM) (HR 1.78 (95%CI 1.17 to 2.69), p = 0.007, AUC 0.58), low albumin concentration (HR 1.58 (95%CI 1.08 to 2.31), p = 0.019, AUC 0.62), low handgrip strength (HR 2.05 (95%CI 1.43 to 2.93), p = 0.001, AUC 0.62) and low muscle radiodensity (HR 1.39 (95%CI 0.90 to 2.16), p = 0.139, AUC 0.63). Combining these parameters resulted in a model with high prognostic power regarding 180-day mortality (overall AUC 0.71). CONCLUSIONS: In this study of inpatients with cancer at nutritional risk, several malnutrition and muscle health parameters emerged as independent prognostic indicators for mortality. The use of these parameters may improve risk stratification and guide nutritional interventions in this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02517476.

Promising new assays and technologies for the diagnosis and management of infectious diseases.

In the first decade of the 21st century, we have seen the completion of the human genome project and marked progress in the human microbiome project. The vast amount of data generated from these efforts combined with advances in molecular and biomedical technologies have led to the development of a multitude of assays and technologies that may be useful in the diagnosis and management of infectious diseases. Here, we identify several new assays and technologies that have recently come into clinical use or have potential for clinical use in the near future. The scope of this review is broad and includes topics such as the serum marker procalcitonin, gene expression profiling, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and nucleic acid aptamers. Principles that underlie each assay or technology, their clinical applications, and potential strengths and limitations are addressed.

Influence of procalcitonin on decision to start antibiotic treatment in patients with a lower respiratory tract infection: insight from the observational multicentric ProREAL surveillance.

Procalcitonin (PCT)-guided antibiotic stewardship is a successful strategy to decrease antibiotic use. We assessed if clinical judgement affected compliance with a PCT-algorithm for antibiotic prescribing in a multicenter surveillance of patients with lower respiratory tract infections (LRTI). Initiation and duration of antibiotic therapy, adherence to a PCT algorithm and outcome were monitored in consecutive adults with LRTI who were enrolled in a prospective observational quality control. We correlated initial clinical judgment of the treating physician with algorithm compliance and assessed the influence of PCT on the final decision to initiate antibiotic therapy. PCT levels correlated with physicians' estimates of the likelihood of bacterial infection (p for trend <0.02). PCT influenced the post-test probability of antibiotic initiation with a greater effect in patients with non-pneumonia LRTI (e.g., for bronchitis: -23 % if PCT ≤ 0.25 µg/L and +31 % if PCT > 0.25 µg/L), in European centers (e.g., in France -22 % if PCT ≤ 0.25 µg/L and +13 % if PCT > 0.25 µg/L) and in centers, which had previous experience with the PCT-algorithm (-16 % if PCT ≤ 0.25 µg/L and +19 % if PCT > 0.25 µg/L). Algorithm non-compliance, i.e. antibiotic prescribing despite low PCT-levels, was independently predicted by the likelihood of a bacterial infection as judged by the treating physician. Compliance was significantly associated with identification of a bacterial etiology (p = 0.01). Compliance with PCT-guided antibiotic stewardship was affected by geographically and culturally-influenced subjective clinical judgment. Initiation of antibiotic therapy was altered by PCT levels. Differential compliance with antibiotic stewardship efforts contributes to geographical differences in antibiotic prescribing habits and potentially influences antibiotic resistance rates.

Influence of diabetes on endothelial cell response during sepsis.

AIMS/HYPOTHESIS: Several endothelial pathways of cell adhesion, coagulation and vascular endothelial growth factor (VEGF) signalling are activated during sepsis. The objective of this analysis was to investigate the influence of diabetes on biomarkers of endothelial cell activation in sepsis. METHODS: This was a prospective observational cohort study of a convenience sample of adult patients (age ≥ 18 years) for whom infection was clinically suspected and who presented to an urban tertiary care emergency department between February 2005 and November 2008. We investigated the association of diabetes and sepsis with various endothelial activation biomarkers of cell adhesion (E-selectin, vascular cell adhesion molecule 1 [VCAM-1] and intercellular adhesion molecule 1 [ICAM-1]), coagulation (plasminogen activator inhibitor 1 [PAI-1]) and VEGF signalling (soluble fms-like tyrosine kinase-1 [sFLT-1]). RESULTS: A total of 207 patients (34% with sepsis, 32% with severe sepsis and 34% with septic shock) were studied, including 63 (30%) with diabetes. Compared with patients without diabetes, patients with diabetes had significantly increased E-selectin and sFLT-1 levels overall; this was most pronounced during septic shock in the stratified analysis. Multivariate models including age, sex, sepsis severity and other variables as potential covariates confirmed the association of diabetes with elevated circulating plasma levels of E-selectin (standardised ß 0.24, p < 0.001) and sFLT-1 (standardised ß 0.19, p < 0.01), but there was no significant association with VCAM-1, ICAM-1 or PAI-1. CONCLUSIONS/INTERPRETATION: During septic shock, patients with diabetes had higher levels of circulating biomarkers of endothelial cell adhesion (E-selectin) and VEGF signalling (sFLT-1). Future studies should address whether enhanced activation of the endothelium places patients with diabetes at increased risk for the development of sepsis and worsening morbidity and mortality.

Prognostic value of procalcitonin in community-acquired pneumonia.

The prognostic value of procalcitonin (PCT) levels to predict mortality and other adverse events in community-acquired pneumonia (CAP) remains undefined. We assessed the performance of PCT overall, stratified into four predefined procalcitonin tiers (< 0.1, 0.1-0.25, > 0.25-0.5, >0.5 µg·L⁻¹) and stratified by Pneumonia Severity Index (PSI) and CURB-65 (confusion, urea >7 mmol·L⁻¹, respiratory frequency ≥ 30 breaths·min⁻¹, systolic blood pressure < 90 mmHg or diastolic blood pressure ≤ 60 mmHg, and age ≥ 65 yrs) risk classes to predict all-cause mortality and adverse events within 30 days follow-up in 925 CAP patients. In receiver operating characteristic curves, initial PCT levels performed only moderately for mortality prediction (area under the curve (AUC) 0.60) and did not improve clinical risk scores. Follow-up measurements on days 3, 5 and 7 showed better prognostic performance (AUCs 0.61, 0.68 and 0.73). For prediction of adverse events, the AUC was 0.66 and PCT significantly improved the PSI (from 0.67 to 0.71) and the CURB-65 (from 0.64 to 0.70). In Kaplan-Meier curves, PCT tiers significantly separated patients within PSI and CURB-65 risk classes for adverse events prediction, but not for mortality. Reclassification analysis confirmed the added value of PCT for adverse event prediction, but not mortality. Initial PCT levels provide only moderate prognostic information concerning mortality risk and did not improve clinical risk scores. However, PCT was helpful during follow-up and for prediction of adverse events and, thereby, improved the PSI and CURB65 scores.

Inflammatory responses predict long-term mortality risk in community-acquired pneumonia.

Long-term outcomes in patients surviving community-acquired pneumonia (CAP) are still incompletely understood. This study investigates the association of clinical parameters and blood markers with long-term mortality. We prospectively followed 877 CAP patients from a previous multicentre trial for 18 months follow-up and investigated all-cause mortality following hospital discharge. Overall mortality was 17.3% (95% CI 14.8-19.8%) with a 12.8% (95% CI 10.9-15.0%) mortality incidence rate per year. Initial risk assignment using the Pneumonia Severity Index was accurate during the 18 month follow-up. Multivariable regression models (hazard ratio, 95% CI) designated the following as independent risk factors for long-term mortality: male sex (1.7, 1.2-2.5); chronic obstructive pulmonary disease (1.5, 1.1-2.1); neoplastic disease (2.5, 1.7-3.7); and highest quartile of peak pro-adrenomedullin level (3.3, 1.7-6.2). Initial presentation with temperature>38.7°C (0.4, 0.2-0.6), chills (0.6, 0.4-0.99) and highest quartile of the inflammatory marker C-reactive-protein (0.3, 0.2-0.5) were independent protective factors. A weighted risk score based on these variables showed good discrimination (area under receiver operating characteristic curve 0.78, 95% CI 0.74-0.82). Pronounced clinical and laboratory signs of systemic inflammatory host response upon initial hospital stay were associated with favourable long-term prognosis. Further studies should address whether closer monitoring of high-risk CAP patients after hospital discharge favourably impacts long-term mortality.

Anterior pituitary axis hormones and outcome in acute ischaemic stroke.

BACKGROUND: Early and accurate prediction of outcome in acute stroke is important and influences risk-optimized therapeutic strategies. Endocrine alterations of the hypothalamic-pituitary axis are amongst the first measurable alterations after cerebral ischaemia. We therefore evaluated the prognostic value of cortisol, triiodothyronine (T3), free thyroxine (fT4), thyroid-stimulating hormone (TSH) and growth hormone (GH) in patients with an acute ischaemic stroke. METHODS: In an observational study including 281 patients with ischaemic stroke, anterior pituitary axis hormones (i.e. cortisol, T3, fT4, TSH and GH) were simultaneously assessed to determine their value to predict functional outcome and mortality within 90 days and 1 year. RESULTS: In receiver operating characteristic curve analysis, the prognostic accuracy of cortisol was higher compared to all measured hormones and was in the range of the National Institutes of Health Stroke Scale (NIHSS). Cortisol was an independent prognostic marker of functional outcome and death [odds ratio (OR) 1.0 (1.0-1.01) and 1.62 (1.37-1.92), respectively, P<0.0002 for both, adjusted for age and the NIHSS] in patients with ischaemic stroke, but added no significant additional predictive value to the clinical NIHSS score. CONCLUSION: Cortisol is an independent prognostic marker for death and functional outcome within 90 days and 1 year in patients with ischaemic stroke. By contrast, other anterior pituitary axis hormones such as peripheral thyroid hormones and GH are only of minor value to predict outcome in stroke.

Effectiveness of a procalcitonin algorithm to guide antibiotic therapy in respiratory tract infections outside of study conditions: a post-study survey.

All published evidence on procalcitonin (PCT)-guided antibiotic therapy was obtained in trials where physicians knew that they were being monitored, possibly resulting in higher adherence to the PCT algorithm. This study investigates the effectiveness of PCT guidance in an observational quality control survey. We monitored antibiotic therapy and algorithm adherence in consecutive patients with respiratory tract infections admitted to the Kantonsspital Aarau, Switzerland, between May 2008 and February 2009. The results were compared to the site-specific results of the former ProHOSP study. Overall and more pronounced for patients with community-acquired pneumonia, the median duration of antibiotic treatment in this survey was shorter than the ProHOSP control patients (6 vs. 7 days, P = 0.048 and 7 vs. 9 days, P < 0.001). In 72.5% of patients, antibiotics were administered according to the prespecified PCT algorithm. No significant differences concerning adverse medical outcome could be detected. This study mirrors the use of PCT-guided antibiotic therapy in clinical practice, outside of trial conditions. If algorithm adherence is reinforced, antibiotic exposure can be markedly reduced with subsequent reduction of antibiotic-associated side effects and antibiotic resistance. The integration of the PCT algorithm into daily practice requires ongoing reinforcement and involves a learning process of the prescribing physicians.

Prognostic value of procalcitonin in Legionella pneumonia.

The diagnostic reliability and prognostic implications of procalcitonin (PCT) (ng/ml) on admission in patients with community-acquired pneumonia (CAP) due to Legionella pneumophila are unknown. We retrospectively analysed PCT values in 29 patients with microbiologically proven Legionella-CAP admitted to the University Hospital Basel, Switzerland, between 2002 and 2007 and compared them to other markers of infection, namely, C-reactive protein (CRP) (mg/l) and leukocyte count (10(9)/l), and two prognostic severity assessment scores (PSI and CURB65). Laboratory analysis demonstrated that PCT values on admission were >0.1 in over 93%, >0.25 in over 86%, and >0.5 in over 82% of patients with Legionella-CAP. Patients with adverse medical outcomes (59%, n = 17) including need for ICU admission (55%, n = 16) and/or inhospital mortality (14%, n = 4) had significantly higher median PCT values on admission (4.27 [IQR 2.46-9.48] vs 0.97 [IQR 0.29-2.44], p = 0.01), while the PSI (124 [IQR 81-147] vs 94 [IQR 75-116], p = 0.19), the CURB65 (2 [IQR 1-2] vs 1 [1-3], p = 0.47), CRP values (282 [IQR 218-343], p = 0.28 vs 201 [IQR 147-279], p = 0.28), and leukocyte counts (12 [IQR 10-21] vs 12 [IQR 9-15], p = 0.58) were similar. In receiver operating curves, PCT concentrations on admission had a higher prognostic accuracy to predict adverse outcomes (AUC 0.78 [95%CI 0.61-96]) as compared to the PSI (0.64 [95%CI 0.43-0.86], p = 0.23), the CURB65 (0.58 [95%CI 0.36-0.79], p = 0.21), CRP (0.61 [95%CI 0.39-0.84], p = 0.19), and leukocyte count (0.57 [95%CI 0.35-0.78], p = 0.12). Kaplan-Meier curves demonstrated that patients with initial PCT values above the optimal cut-off of 1.5 had a significantly higher risk of death and/or ICU admission (log rank p = 0.003) during the hospital stay. In patients with CAP due to Legionella, PCT levels on admission might be an interesting predictor for adverse medical outcomes.

How to: implement procalcitonin testing in my practice.

BACKGROUND: Adding procalcitonin (PCT) to antibiotic stewardship algorithms may improve antibiotic use. However, PCT protocols need to be adapted to clinical settings and patient populations. OBJECTIVES: To review PCT use in different medical settings and patient populations. SOURCES: Most recent trials and meta-analyses investigating PCT for antibiotic stewardship were reviewed. CONTENT: Several trials found PCT-guided antibiotic stewardship to reduce antibiotic exposure and associated side-effects among patients with respiratory infection and sepsis. Decisions regarding antibiotic use in an individual patient are complex and should be based on the pre-test probability for bacterial infection, the severity of presentation and the results of PCT. In the context of a low pre-test probability for bacterial infections and a low-risk patient, a low PCT level helps to rule out bacterial infection and empiric antibiotic therapy can be avoided. In the context of a high pre-test probability for bacterial infections and/or a high-risk patient with sepsis, monitoring of PCT over time helps to track the resolution of infection and decisions regarding early stop of antibiotic treatment. Although these concepts have been successful in several respiratory infection and sepsis trials, some studies failed to show an added benefit of PCT due to factors such as low protocol adherence and relying on single rather than repeat PCT measurements. IMPLICATION: As an adjunct to other clinical and laboratory parameters, PCT provides information about risk for bacterial infection and resolution of infection, and improves antibiotic stewardship decisions, thereby offering more individualized treatment courses with overall reduced antibiotic exposure.

Serum procalcitonin for discrimination between septic and non-septic arthritis.

BACKGROUND: Early differentiation between septic and non-septic arthritis is difficult. A previous study showed promising diagnostic accuracy of serum Procalcitonin (PCT) in septic arthritis, limited by a low sensitive PCT test kit. OBJECTIVE: To investigate the diagnostic value of PCT in patients with septic and non-septic arthritis using a novel test with low detection limit. METHODS: Forty-two patients, 28 with non-septic and 14 with septic arthritis were prospectively included. For each patient, gram stain, culture and polarization microscopy of synovial fluid was done and PCT, C-reactive protein (CRP), white blood cell count, uric acid and blood cultures were taken. Patients with septic arthritis, patients with non-septic arthritis with and without concomitant infection were compared. RESULTS: Patients with septic arthritis had a significant higher PCT concentration than patients with non-septic arthritis (p<0.0001). At a cut-off of 0.1 (0.25) ng/ml, sensitivity for septic arthritis was 100(93)% and specificity 46(75)%. Specificity rose to 93% after exclusion of patients with non-septic arthritis and concomitant infection. Both sensitivity and specificity for the diagnosis of septic arthritis were higher for PCT than CRP. CONCLUSIONS: Our data suggest that PCT seems to be a highly sensitive and specific marker for septic arthritis, depending on the clinical setting. Further studies are warranted.

Revisiting nutritional support for allogeneic hematologic stem cell transplantation-a systematic review.

In 2009, the American Society of Parenteral and Enteral Nutrition and its European counterpart (Euopean Society for Parenteral and Enteral Nutrition) published guidelines regarding nutritional support of patients with hematologic stem cell transplantation. Our aim was to do an up-to-date literature review regarding benefit of nutritional interventions and treatment recommendations. We searched MEDLINE, EMBASE and Cochrane Library for interventional and observational clinical studies. We extracted data based on a predefined case report form and assessed bias. Out of 459 potential abstracts, 13 studies of mostly moderate quality with a total of 18 167 patients were included. Two very large trials reported negative associations of malnutrition and survival, transplant-related mortality and relapse risk. Some trials found enteral nutrition (EN) to be as effective as parenteral nutrition (PN) with lower complication rates. In addition, EN was associated with better survival, less acute GvHD and faster neutrophil recovery. A neutropenic diet was not superior regarding overall survival, but in contrast resulted in higher infection risk. Current moderate quality studies show negative associations of malnutrition and clinical outcomes, with EN being superior to PN. There was no benefit of neutropenic diets. Large, randomized controlled studies are needed to better understand optimal nutritional support in this patient population.