Association of endothelial activation assessed through endothelin-I precursor peptide measurement with mortality in COVID-19 patients: an observational analysis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has been linked to thrombotic complications and endothelial dysfunction. We assessed the prognostic implications of endothelial activation through measurement of endothelin-I precursor peptide (proET-1), the stable precursor protein of Endothelin-1, in a well-defined cohort of patients hospitalized with COVID-19. METHODS: We measured proET-1 in 74 consecutively admitted adult patients with confirmed COVID-19 and compared its prognostic accuracy to that of patients with community-acquired pneumonia (n = 876) and viral bronchitis (n = 371) from a previous study by means of logistic regression analysis. The primary endpoint was all-cause 30-day mortality. RESULTS: Overall, median admission proET-1 levels were lower in COVID-19 patients compared to those with pneumonia and exacerbated bronchitis, respectively (57.0 pmol/l vs. 113.0 pmol/l vs. 96.0 pmol/l, p < 0.01). Although COVID-19 non-survivors had 1.5-fold higher admission proET-1 levels compared to survivors (81.8 pmol/l [IQR: 76 to 118] vs. 53.6 [IQR: 37 to 69]), no significant association of proET-1 levels and mortality was found in a regression model adjusted for age, gender, creatinine level, diastolic blood pressure as well as cancer and coronary artery disease (adjusted OR 0.1, 95% CI 0.0009 to 14.7). In patients with pneumonia (adjusted OR 25.4, 95% CI 5.1 to 127.4) and exacerbated bronchitis (adjusted OR 120.1, 95% CI 1.9 to 7499) we found significant associations of proET-1 and mortality. CONCLUSIONS: Compared to other types of pulmonary infection, COVID-19 shows only a mild activation of the endothelium as assessed through measurement of proET-1. Therefore, the high mortality associated with COVID-19 may not be attributed to endothelial dysfunction by the surrogate marker proET-1.

Phlegmasia cerulea dolens - an uncommon but alarming manifestation of deep vein thrombosis.

In phlegmasia cerulea dolens (PCD), immediate diagnosis and prompt treatment is crucial for limb salvage. Aggressive treatment options including venous intervention, thrombolysis and/or surgical thrombectomy should be considered. Due to the lack of data, the most appropriate intervention depends upon etiology of PCD, clinical presentation and patient's bleeding risk.

The Shapiro-Procalcitonin algorithm (SPA) as a decision tool for blood culture sampling: validation in a prospective cohort study.

PURPOSE: Blood cultures (BC) are the gold standard for bacteremia detection despite a relatively low diagnostic yield and high costs. A retrospective study reported high predictive values for BC positivity when combining the clinical Shapiro score with procalcitonin (PCT). METHODS: Single-center, prospective cohort study between 01/2016 and 02/2017 to validate SPA algorithm, including a modified Shapiro score ≥ 3 points (S) PLUS admission PCT > 0.25 µg/l (P), or presence of overruling safety criteria (A) in patients with systemic inflammatory response syndrome. The diagnostic yield of SPA compared to non-standardized clinical judgment in predicting BC positivity was calculated and results presented as odds ratios (OR) with 95% confidence intervals. RESULTS: Of 1438 patients with BC sampling, 215 (15%) had positive BC which increased to 31% (173/555) in patients fulfilling SP criteria (OR for BC positivity 9.07 [6.34-12.97]). When adding 194 patients with overruling safety criteria (i.e., SPA), OR increased to 11.12 (6.99-17.69), although BC positivity slightly decreased to 26%. With an area under the receiver operating curve of 0.742, SPA indicated better diagnostic performance than its individual components. Positive BC in 689 patients not fulfilling SPA (sampling according to non-standardized clinical judgment) were rare (3%; OR for BC positivity 0.09 [0.06-0.14]). Eight out of 21 missed pathogens were still identified by sampling the primary infection focus. CONCLUSIONS: This study validates the high predictive value of SPA for bacteremia, increasing true BC positivity from 15 to 26%. Restricting BC sampling to SPA would have reduced BC sampling by 48%, while still detecting 194/215 organisms (90%), which makes SPA a valuable diagnostic stewardship tool.

What Are They Worth? Six 30-Day Readmission Risk Scores for Medical Inpatients Externally Validated in a Swiss Cohort.

BACKGROUND: Several clinical risk scores for unplanned 30-day readmission have been published, but there is a lack of external validation and head-to-head comparison. OBJECTIVE: Retrospective replication of six clinical risk scores (LACE, HOSPITAL, SEMI, RRS, PARA, Tsui et al.)f DESIGN: Models were fitted with the original intercept and beta coefficients as reported. Otherwise, a logistic model was refitted (SEMI and Tsui et al). We performed subgroup analyses on main admission specialty. This report adheres to the TRIPOD statement for reporting of prediction models. PARTICIPANTS: We used our prospective cohort of 15,639 medical patients from a Swiss tertiary care institution from 2016 through 2018. MAIN MEASURES: Thirty-day readmission rate and area under the curve (AUC < 0.50 worse than chance, > 0.70 acceptable, > 0.80 excellent) CONCLUSIONS: Among several readmission risk scores, HOSPITAL, PARA, and the score from Tsui et al. showed the best predictive abilities and have high potential to improve patient care. Interventional research is now needed to understand the effects of these scores when used in clinical routine. KEY RESULTS: Among the six risk scores externally validated, calibration of the models was overall poor with overprediction of events, except for the HOSPITAL and the PARA scores. Discriminative abilities (AUC) were as follows: LACE 0.53 (95% CI 0.50-0.56), HOSPITAL 0.73 (95% CI 0.72-0.74), SEMI 0.47 (95% CI 0.46-0.49), RRS 0.64 (95% CI 0.62-0.66), PARA 0.72 (95% CI 0.72-0.74), and the score from Tsui et al. 0.73 (95% CI 0.72-0.75). Performance in subgroups did not differ from the overall performance, except for oncology patients in the PARA score (0.57, 95% CI 0.54-0.60), and nephrology patients in the SEMI index (0.25, 95% CI 0.18-0.31), respectively.

Outcome of Clostridioides difficile infections treated in a Swiss tertiary care hospital: an observational study.

AIMS OF THE STUDY: Clostridioides difficile infection (CDI) is associated with high morbidity, recurrence rates and mortality. We assessed the local epidemiology, treatment outcomes and risk factors for recurrence and mortality. METHODS: This was a retrospective study of all adult CDI episodes treated in our tertiary care hospital between 2014 and 2016. Patients were followed up for 60 days, with recurrence and death as endpoints. Antibiotic treatment as well as epidemiological, clinical and laboratory parameters were studied using logistic regression analysis. Risk factors for recurrent CDI (age >70 years, haematological malignancy, chronic kidney disease, severe infection, continued antibiotics other than for CDI, proton pump inhibitor / antacid use) and indicators of severe CDI (temperature ≥38.5°C, leucocytes >15 × 109/l, creatinine increase ≥1.5 × baseline, albumin <25 g/l) were analysed. We considered episodes with ≥2 indicators as severe. RESULTS: We identified 210 CDI episodes (66 severe) in 191 patients with a median age of 71 years (interquartile range 59–79). Hypervirulent ribotype 027/NAP1/BI accounted for four episodes (2%). Overall, 176, 30 and 4 patients, respectively, received a first, second and third treatment. Metronidazole was used in 94% of the first episodes and in 73% and 50% of the first and second recurrences, respectively. The recurrence rate after the first metronidazole treatment was 20%. Recurrence rates were higher when ≥2 risk factors were present (25 vs 10%, p = 0.03). The 60-day mortality was 17% (4% attributable to CDI) and increased with the presence of ≥2 indicators of severe CDI. CONCLUSIONS: The high 60-day mortality suggests that CDI is a strong indicator of frailty. Metronidazole was associated with low recurrence rates at minimal costs in patients with uncomplicated CDI, but had relevant shortcomings in patients with severe CDI and/or a high risk of recurrence, suggesting that these vulnerable patients might better be treated with oral vancomycin and fidaxomicin, according to the latest guidelines.  .

Diagnostic and prognostic value of the D-dimer test in emergency department patients: secondary analysis of an observational study.

Background D-dimer measurement improves the rule-out of thromboembolic disease. However, little is known about the risk of false positive results for the diagnosis of thromboembolic disease and its prognostic value. Herein, we investigated factors influencing the accuracy of D-dimer and its prognostic value in a large cohort of emergency department (ED) patients. Methods This is a secondary analysis of a prospective observational single center, cohort study. Consecutive patients, for whom a D-dimer test was requested by the treating physician, were included. Associations of clinical parameters on admission with false positive D-dimer results for the diagnosis of thromboembolic disease were investigated with logistic regression analysis. Results A total of 3301 patients were included, of which 203 (6.1%) had confirmed thromboembolic disease. The negative and positive predictive values of the D-dimer test at the 0.5 mg/L cut-off were 99.9% and 11.4%, respectively. Several factors were associated with positive D-dimer results potentially falsely indicating thromboembolic disease in multivariate analysis including advanced age (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.04-1.05, p < 0.001), congestive heart failure (CHF) (OR 2.79, 95% CI 1.77-4.4, p < 0.01), renal failure (OR 2.00, 95% CI 1.23-3.24, p = 0.005), history of malignancy (OR 2.6, 95% CI 1.57-4.31, p < 0.001), C-reactive protein (CRP) (OR 1.02, 95% CI 1.01-1.02, p < 0.001) and glomerular filtration rate (GFR) (OR 0.99, 95% CI 0.99-1.00, p = 0.003). Regarding its prognostic value, D-dimer was associated with a 30-day mortality (adjusted OR 1.05, 95% CI 1.02-1.09, p = 0.003) with an area under the curve (AUC) of 0.79. Conclusions While D-dimer allows an accurate rule-out of thromboembolic disease, its positive predictive value in routine ED patients is limited and largely influenced by age, comorbidities and acute disease factors. The strong prognostic value of D-dimer in this population warrants further investigation.

A high C-reactive protein/procalcitonin ratio predicts Mycoplasma pneumoniae infection.

Background Discriminating Mycoplasma pneumoniae (MP) from Streptococcus pneumoniae (SP) and viral etiologies of community-acquired pneumonia (CAP) is challenging but has important implications regarding empiric antibiotic therapy. We investigated patient parameters upon hospital admission to predict MP infection. Methods All patients hospitalized in a tertiary care hospital between 2013 and 2017 for CAP with a confirmed etiology were analyzed using logistic regression analyses and area under the receiver operator characteristics (ROC) curves (AUC) for associations between demographic, clinical and laboratory features and the causative pathogen. Results We analyzed 568 patients with CAP, including 47 (8%) with MP; 152 (27%) with SP and 369 (65%) with influenza or other viruses. Comparing MP and SP by multivariate logistic regression analysis, younger age (odds ration [OR] 0.56 per 10 years, 95% CI 0.42-0.73), a lower neutrophil/lymphocyte ratio (OR 0.9, 0.82-0.99) and an elevated C-reactive protein/procalcitonin (CRP/PCT) ratio (OR 15.04 [5.23-43.26] for a 400 mg/µg cut-off) independently predicted MP. With a ROC curve AUC of 0.91 (0.80 for the >400 mg/µg cutoff), the CRP/PCT ratio was the strongest predictor of MP vs. SP. The discriminatory value resulted from significantly lower PCT values (p < 0.001) for MP, while CRP was high in both groups (p = 0.057). Comparing MP and viral infections showed similar results with again the CRP/PCT ratio providing the best information (AUC 0.83; OR 5.55 for the >400 mg/µg cutoff, 2.26-13.64). Conclusions In patients hospitalized with CAP, a high admission CRP/PCT ratio predicts M. pneumoniae infection and may improve empiric management.

Combination of the National Early Warning Score (NEWS) and inflammatory biomarkers for early risk stratification in emergency department patients: results of a multinational, observational study.

OBJECTIVES: The National Early Warning Score (NEWS) helps to estimate mortality risk in emergency department (ED) patients. This study aimed to investigate whether the prognostic value of the NEWS at ED admission could be further improved by adding inflammatory blood markers (ie, white cell count (WCC), procalcitonin (PCT) and midregional-proadrenomedullin (MR-proADM). DESIGN: Secondary analysis of a multinational, observational study (TRIAGE study, March 2013-October 2014). SETTING: Three tertiary care centres in France, Switzerland and the USA. PARTICIPANTS: A total of 1303 adult medical patients with complete NEWS data seeking ED care were included in the final analysis. NEWS was calculated retrospectively based on admission data. MAIN OUTCOME MEASURES: The primary outcome was all-cause 30-day mortality. Secondary outcome was intensive care unit (ICU) admission. We used multivariate regression analyses to investigate associations of NEWS and blood markers with outcomes and area under the receiver operating curve (AUC) as a measure of discrimination. RESULTS: Of the 1303 included patients, 54 (4.1%) died within 30 days. The NEWS alone showed fair prognostic accuracy for all-cause 30-day mortality (AUC 0.73), with a multivariate adjusted OR of 1.26 (95% CI 1.13 to 1.40, p<0.001). The AUCs for the prediction of mortality using the inflammatory markers WCC, PCT and MR-proADM were 0.64, 0.71 and 0.78, respectively. Combining NEWS with all three blood markers or only with MR-proADM clearly improved discrimination with an AUC of 0.82 (p=0.002). Combining the three inflammatory markers with NEWS improved prediction of ICU admission (AUC 0.70vs0.65 when using NEWS alone, p=0.006). CONCLUSION: NEWS is helpful in risk stratification of ED patients and can be further improved by the addition of inflammatory blood markers. Future studies should investigate whether risk stratification by NEWS in addition to biomarkers improve site-of-care decision in this patient population. TRIAL REGISTRATION NUMBER: NCT01768494; Post-results.

Procalcitonin-guided Antibiotic Treatment in Patients With Positive Blood Cultures: A Patient-level Meta-analysis of Randomized Trials.

BACKGROUND: Whether procalcitonin (PCT)-guided antibiotic management in patients with positive blood cultures is safe remains understudied. We performed a patient-level meta-analysis to investigate effects of PCT-guided antibiotic management in patients with bacteremia. METHODS: We extracted and analyzed individual data of 523 patients with positive blood cultures included in 13 trials, in which patients were randomly assigned to receive antibiotics based on PCT levels (PCT group) or a control group. The main efficacy endpoint was duration of antibiotic treatment. The main safety endpoint was mortality within 30 days. RESULTS: Mean duration of antibiotic therapy was significantly shorter for 253 patients who received PCT-guided treatment than for 270 control patients (-2.86 days [95% confidence interval [CI], -4.88 to -.84]; P = .006). Mortality was similar in both arms (16.6% vs 20.0%; P = .263). In subgroup analyses by type of pathogen, we noted a trend of shorter mean antibiotic durations in the PCT arm for patients infected with gram-positive organisms or Escherichia coli and significantly shorter treatment for subjects with pneumococcal bacteremia. In analysis by site of infection, antibiotic exposure was shortened in PCT subjects with Streptococcus pneumoniae respiratory infection and those with E. coli urogenital infections. CONCLUSIONS: This meta-analysis of patients with bacteremia receiving PCT-guided antibiotic management demonstrates lower antibiotic exposure without an apparent increase in mortality. Few differences were demonstrated in subgroup analysis stratified by type or site of infection but notable for decreased exposure in patients with pneumococcal pneumonia and E. coli urogenital infections.

Peripheral monocytosis as a predictive factor for adverse outcome in the emergency department: Survey based on a register study.

Monocytosis is associated with chronic infections such as tuberculosis or endocarditis as well as rheumatic and myeloproliferative disorders. Monocytes are also involved in the pathogenesis of atherosclerosis, coronary artery disease, and stroke. The value of monocytosis as a prognostic marker in different diagnostic groups in the emergency setting, however, has not been investigated so far.The aim of the article is to study monocytosis as an outcome factor in the emergency setting.In a Swiss register study, we analyzed monocyte counts in 4238 patients aged >18 years who were admitted to the emergency department of a regional tertiary care hospital. Monocytosis was defined as 0.8×10 cells/L. Diagnoses were grouped into infection, cardiovascular, neurological, metabolic, gastrointestinal, pulmonary, or other. Thirty-day mortality was defined as the primary endpointA total of 1217 patients with monocytosis were identified. Patients with monocytosis at admission suffered more frequently from respiratory symptoms (17.7% vs 8.9%, P <.001) and infection as the final diagnosis (20.8% vs 10.3%, P <.001) while neurological diagnoses were significantly lower in the monocytosis group (15.3% vs 30.9%, P <.001). Patients with monocytosis suffered from more comorbidities such as congestive heart failure, chronic obstructive pulmonary disease, tumor, diabetes, or renal failure but not dementia. When adjusted for age, gender, comorbidities, and main diagnosis, the 30-day mortality (P = .002) and length of stay (P = .001) were significantly higher in patients with monocytosis. The 30-day mortality in patients with monocytosis was most notably influenced by a cardiological diagnosis (odds ratio 3.91).An increased monocyte count predicts adverse outcome in patients admitted to the emergency department. Mechanistic studies will be necessary to specify the potentially detrimental role of monocytosis in critical illness.

Fungemia and necrotic lymph node infection with Sporopachydermia cereana in a patient with acute myeloid leukemia.

Sporopachydermia cereana is a rare yeast found in necrotic cactus tissue, predominantly in the Americas. Infection in humans with clinical data has only been reported in four patients so far, all of whom died, either directly from the pathogen or from other complications of immunosuppression. Treatment of the yeast is complicated by difficulties in identification of the pathogen with conventional diagnostic techniques and by intrinsic resistance to echinocandins. The first patient to survive a disseminated infection with S. cereana is presented herein. The patient had acute myeloid leukemia and was treated successfully with antifungal therapy and subsequently underwent a successful allogeneic hematopoietic stem cell transplantation.

Procalcitonin improves the Glasgow Prognostic Score for outcome prediction in emergency patients with cancer: a cohort study.

The Glasgow Prognostic Score (GPS) is useful for predicting long-term mortality in cancer patients. Our aim was to validate the GPS in ED patients with different cancer-related urgency and investigate whether biomarkers would improve its accuracy. We followed consecutive medical patients presenting with a cancer-related medical urgency to a tertiary care hospital in Switzerland. Upon admission, we measured procalcitonin (PCT), white blood cell count, urea, 25-hydroxyvitamin D, corrected calcium, C-reactive protein, and albumin and calculated the GPS. Of 341 included patients (median age 68 years, 61% males), 81 (23.8%) died within 30 days after admission. The GPS showed moderate prognostic accuracy (AUC 0.67) for mortality. Among the different biomarkers, PCT provided the highest prognostic accuracy (odds ratio 1.6 (95% confidence interval 1.3 to 1.9), P < 0.001, AUC 0.69) and significantly improved the GPS to a combined AUC of 0.74 (P = 0.007). Considering all investigated biomarkers, the AUC increased to 0.76 (P < 0.001). The GPS performance was significantly improved by the addition of PCT and other biomarkers for risk stratification in ED cancer patients. The benefit of early risk stratification by the GPS in combination with biomarkers from different pathways should be investigated in further interventional trials.

Streamlining antibiotic therapy with procalcitonin protocols: consensus and controversies.

Accumulating evidence supports procalcitonin (PCT) as an accurate surrogate biomarker for likelihood and severity of bacterial infections. In community-acquired pneumonia and other respiratory infections, PCT-guided antibiotic therapy algorithms resulted in reduced antibiotic exposure while maintaining a similar or even better level of safety compared with standard care. Reductions in antibiotic use translate into lower treatment costs, decreased risk of side effects and decreased bacterial multiresistance. This is especially important, as acute respiratory infections represent the most frequent reason for antibiotic prescriptions worldwide. Still, there is some controversy about the benefits of PCT measurement in sepsis patients in the intensive care unit and for nonrespiratory infections. Highly sensitive PCT assays are readily available in many hospitals today, and point-of-care assays with high enough sensitivity for antibiotic guidance are expected to be available soon. Herein, the authors provide an overview of recent studies evaluating PCT in different clinical situations and an outlook of currently enrolling or upcoming interventional trials.