Cardiovascular risk in patients with acromegaly vs. non-functioning pituitary adenoma following pituitary surgery: an active-comparator cohort study.

PURPOSE: Given the increased cardio-metabolic risk in patients with acromegaly, this study compared cardiovascular outcomes, mortality, and in-hospital outcomes between patients with acromegaly and non-functioning pituitary adenoma (NFPA) following pituitary surgery. METHODS: This was a nationwide cohort study using data from hospitalized patients with acromegaly or NFPA undergoing pituitary surgery in Switzerland between January 2012 and December 2021. Using 1:3 propensity score matching, eligible acromegaly patients were paired with NFPA patients who underwent pituitary surgery, respectively. The primary outcome comprised a composite of cardiovascular events (myocardial infarction, cardiac arrest, ischemic stroke, hospitalization for heart failure, unstable angina pectoris, cardiac arrhythmias, intracranial hemorrhage, hospitalization for hypertensive crisis) and all-cause mortality. Secondary outcomes included individual components of the primary outcome, surgical re-operation, and various hospital-associated outcomes. RESULTS: Among 231 propensity score-matched patients with acromegaly and 491 with NFPA, the incidence rate of the primary outcome was 8.18 versus 12.73 per 1,000 person-years (hazard ratio [HR], 0.64; [95% confidence interval [CI], 0.31-1.32]). Mortality rates were numerically lower in acromegaly patients (2.43 vs. 7.05 deaths per 1,000 person-years; HR, 0.34; [95% CI, 0.10-1.17]). Individual components of the primary outcome and in-hospital outcomes showed no significant differences between the groups. CONCLUSION: This cohort study did not find an increased risk of cardiovascular outcomes and mortality in patients with acromegaly undergoing pituitary surgery compared to surgically treated NFPA patients. These findings suggest that there is no legacy effect regarding higher cardio-metabolic risk in individuals with acromegaly once they receive surgical treatment.

Association of admission cortisol levels with outcomes and treatment response in patients at nutritional risk : A secondary analysis of a randomized clinical trial.

INTRODUCTION: Cortisol is a metabolically active stress hormone that may play a role in the pathogenesis of malnutrition. We studied the association between admission cortisol levels and nutritional parameters, disease severity, and response to nutritional support among medical inpatients at nutritional risk. METHODS: Admission cortisol was measured in a subset of 764 patients participating in the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a multicentre, randomized-controlled trial that compared individualized nutritional support with usual nutritional care. RESULTS: Overall, mean cortisol levels were 570 (± 293) nmol/L and significantly higher in patients with high nutritional risk (NRS ≥ 5) and in patients reporting loss of appetite. Cortisol levels in the highest quartile (> 723 nmol/l) were associated with adverse outcomes including mortality at 30 days and 5 years (adjusted HR 2.31, [95%CI 1.47 to 3.62], p = 0.001 and 1.51, [95%CI 1.23 to 1.87], p < 0.001). Nutritional treatment tended to be more effective regarding mortality reduction in patients with high vs. low cortisol levels (adjusted OR of nutritional support 0.54, [95%CI 0.24 to 1.24] vs. OR 1.11, [95%CI 0.6 to 2.04], p for interaction = 0.134). This effect was most pronounced in the subgroup of patients with severe malnutrition (NRS 2002 ≥ 5, p for interaction = 0.047). CONCLUSION: This secondary analysis of a randomized nutritional trial suggests that cortisol levels are linked to nutritional and clinical outcome among multimorbid medical patients at nutritional risk and may help to improve risk assessment, as well as response to nutritional treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02517476.

Adjunct prednisone in community-acquired pneumonia: 180-day outcome of a multicentre, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Several trials and meta-analyses found a benefit of adjunct corticosteroids for community-acquired pneumonia with respect to short-term outcome, but there is uncertainty about longer-term health effects. Herein, we evaluated clinical outcomes at long term in patients participating in the STEP trial (Corticosteroid Treatment for Community-Acquired Pneumonia). METHODS: This predefined secondary analysis investigated 180-day outcomes in 785 adult patients hospitalized with community-acquired pneumonia included in STEP, a randomised, placebo-controlled, double-blind trial. The primary endpoint was time to death from any cause at 180 days verified by telephone interview. Additional secondary endpoints included pneumonia-related death, readmission, recurrent pneumonia, secondary infections, new hypertension, and new insulin dependence. RESULTS: From the originally included 785 patients, 727 were available for intention-to-treat analysis at day 180. There was no difference between groups with respect to time to death from any cause (HR for corticosteroid use 1.15, 95% CI 0.68 to 1.95, p = 0.601). Compared to placebo, corticosteroid-treated patients had significantly higher risks for recurrent pneumonia (OR 2.57, 95% CI 1.29 to 5.12, p = 0.007), secondary infections (OR 1.94, 95% CI 1.25 to 3.03, p = 0.003) and new insulin dependence (OR 8.73, 95% CI 1.10 to 69.62, p = 0.041). There was no difference regarding pneumonia-related death, readmission and new hypertension. CONCLUSIONS: In patients with community-acquired pneumonia, corticosteroid use was associated with an increased risk for recurrent pneumonia, secondary infections and new insulin dependence at 180 days. Currently, it is uncertain whether these long-term adverse effects outweigh the short-term effects of corticosteroids in moderate CAP. TRIAL REGISTRATION: This trial was registered with ClinicalTrials. gov, number NCT00973154 before the recruitment of the first patient. First posted: September 9, 2009. Last update posted: April 21, 2015.

Call, chosen, HA2T2, ANDC: validation of four severity scores in COVID-19 patients.

PURPOSE: To externally validate four previously developed severity scores (i.e., CALL, CHOSEN, HA2T2 and ANDC) in patients with COVID-19 hospitalised in a tertiary care centre in Switzerland. METHODS: This observational analysis included adult patients with a real-time reverse-transcription polymerase chain reaction or rapid-antigen test confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection hospitalised consecutively at the Cantonal Hospital Aarau from February to December 2020. The primary endpoint was all-cause in-hospital mortality. The secondary endpoint was disease progression, defined as needing invasive ventilation, ICU admission or death. RESULTS: From 399 patients (mean age 66.6 years ± 13.4 SD, 68% males), we had complete data for calculating the CALL, CHOSEN, HA2T2 and ANDC scores in 297, 380, 151 and 124 cases, respectively. Odds ratios for all four scores showed significant associations with mortality. The discriminative power of the HA2T2 score was higher compared to CALL, CHOSEN and ANDC scores [area under the curve (AUC) 0.78 vs. 0.65, 0.69 and 0.66, respectively]. Negative predictive values (NPV) for mortality were high, particularly for the CALL score (≥ 6 points: 100%, ≥ 9 points: 95%). For disease progression, discriminative power was lower, with the CHOSEN score showing the best performance (AUC 0.66). CONCLUSION: In this external validation study, the four analysed scores had a lower performance compared to the original cohorts regarding prediction of mortality and disease progression. However, all scores were significantly associated with mortality and the NPV of the CALL and CHOSEN scores in particular allowed reliable identification of patients at low risk, making them suitable for outpatient management.

Glucose control after glucocorticoid administration in hospitalized patients - a retrospective analysis.

BACKGROUND: Glucocorticoid (GC)-induced hyperglycemia is a frequent adverse effect in hospitalized patients. Guidelines recommend insulin treatment to a target range of 6-10 mmol/L (108-180 mg/dl), but efficacies of particular regimes have not been well-studied. METHODS: In this retrospective cohort study, hospitalized patients receiving GCs at the medical ward were analyzed by treatment (basal-bolus vs. bolus-only vs. pre-mixed insulin) and compared to a non-insulin-therapy reference group. Coefficients of glucose variation (CV), percentage of glucose readings in range (4-10 mmol/L (72-180 mg/dl)) and hypoglycemia (< 4 mmol/L (< 72 mg/dl)) were evaluated. RESULTS: Of 2424 hospitalized patients receiving systemic GCs, 875 (36%) developed GC-induced hyperglycemia. 427 patients (17%) had a previous diagnosis of diabetes. Adjusted relative risk ratios (RRR) for the top tertile of CV (> 29%) were 1.47 (95% Cl 1.01-2.15) for bolus-only insulin, 4.77 (95% CI 2.67-8.51) for basal-bolus insulin, and 4.98 (95% CI 2.02-12.31) for premixed insulin, respectively. Adjusted RRR for percentages of glucose readings in range were 0.98 (95% Cl 0.97-0.99) for basal-bolus insulin, 0.99 (95% Cl 0.98-1.00) for premixed insulin, and 1.01 (95% Cl 1.00-1.01) for bolus-only insulin, respectively. Adjusted RRR for hypoglycemia was 13.17 (95% Cl 4.35-39.90) for basal-bolus insulin, 8.92 (95% Cl 2.60-30.63) for premixed insulin, and 2.99 (95% Cl 1.01-8.87) for bolus-only insulin, respectively. CONCLUSIONS: Current guidelines recommend a basal-bolus regimen for treatment of GC-induced hyperglycemia, but we found similar outcomes with pre-mixed and bolus-only insulin regimens. As GC-induced hyperglycemia is a frequent issue in hospitalized patients, it might be reasonable to prospectively study the ideal regimen.

Effect of Bedside Compared With Outside the Room Patient Case Presentation on Patients' Knowledge About Their Medical Care : A Randomized, Controlled, Multicenter Trial.

BACKGROUND: Although bedside case presentation contributes to patient-centered care through active patient participation in medical discussions, the complexity of medical information and jargon-induced confusion may cause misunderstandings and patient discomfort. OBJECTIVE: To compare bedside versus outside the room patient case presentation regarding patients' knowledge about their medical care. DESIGN: Randomized, controlled, parallel-group trial. (ClinicalTrials.gov: NCT03210987). SETTING: 3 Swiss teaching hospitals. PATIENTS: Adult medical patients who were hospitalized. INTERVENTION: Patients were randomly assigned to bedside or outside the room case presentation. MEASUREMENTS: The primary endpoint was patients' average knowledge of 3 dimensions of their medical care (each rated on a visual analogue scale from 0 to 100): understanding their disease, the therapeutic approach being used, and further plans for care. RESULTS: Compared with patients in the outside the room group (n = 443), those in the bedside presentation group (n = 476) reported similar knowledge about their medical care (mean, 79.5 points [SD, 21.6] vs. 79.4 points [SD, 19.8]; adjusted difference, 0.09 points [95% CI, -2.58 to 2.76 points]; P = 0.95). Also, an objective rating of patient knowledge by the study team was similar for the 2 groups, but the bedside presentation group had higher ratings of confusion about medical jargon and uncertainty caused by team discussions. Bedside ward rounds were more efficient (mean, 11.89 minutes per patient [SD, 4.92] vs. 14.14 minutes per patient [SD, 5.65]; adjusted difference, -2.31 minutes [CI, -2.98 to -1.63 minutes]; P < 0.001). LIMITATION: Only Swiss hospitals and medical patients were included. CONCLUSION: Compared with outside the room case presentation, bedside case presentation was shorter and resulted in similar patient knowledge, but sensitive topics were more often avoided and patient confusion was higher. Physicians presenting at the bedside need to be skilled in the use of medical language to avoid confusion and misunderstandings. PRIMARY FUNDING SOURCE: Swiss National Foundation (10531C_ 182422).

A Copeptin-Based Approach in the Diagnosis of Diabetes Insipidus.

BACKGROUND: The indirect water-deprivation test is the current reference standard for the diagnosis of diabetes insipidus. However, it is technically cumbersome to administer, and the results are often inaccurate. The current study compared the indirect water-deprivation test with direct detection of plasma copeptin, a precursor-derived surrogate of arginine vasopressin. METHODS: From 2013 to 2017, we recruited 156 patients with hypotonic polyuria at 11 medical centers to undergo both water-deprivation and hypertonic saline infusion tests. In the latter test, plasma copeptin was measured when the plasma sodium level had increased to at least 150 mmol per liter after infusion of hypertonic saline. The primary outcome was the overall diagnostic accuracy of each test as compared with the final reference diagnosis, which was determined on the basis of medical history, test results, and treatment response, with copeptin levels masked. RESULTS: A total of 144 patients underwent both tests. The final diagnosis was primary polydipsia in 82 patients (57%), central diabetes insipidus in 59 (41%), and nephrogenic diabetes insipidus in 3 (2%). Overall, among the 141 patients included in the analysis, the indirect water-deprivation test determined the correct diagnosis in 108 patients (diagnostic accuracy, 76.6%; 95% confidence interval [CI], 68.9 to 83.2), and the hypertonic saline infusion test (with a copeptin cutoff level of >4.9 pmol per liter) determined the correct diagnosis in 136 patients (96.5%; 95% CI, 92.1 to 98.6; P<0.001). The indirect water-deprivation test correctly distinguished primary polydipsia from partial central diabetes insipidus in 77 of 105 patients (73.3%; 95% CI, 63.9 to 81.2), and the hypertonic saline infusion test distinguished between the two conditions in 99 of 104 patients (95.2%; 95% CI, 89.4 to 98.1; adjusted P<0.001). One serious adverse event (desmopressin-induced hyponatremia that resulted in hospitalization) occurred during the water-deprivation test. CONCLUSIONS: The direct measurement of hypertonic saline-stimulated plasma copeptin had greater diagnostic accuracy than the water-deprivation test in patients with hypotonic polyuria. (Funded by the Swiss National Foundation and others; ClinicalTrials.gov number, NCT01940614 .).

Association of mannose-binding lectin, ficolin-2 and immunoglobulin concentrations with future exacerbations in patients with chronic obstructive pulmonary disease: secondary analysis of the randomized controlled REDUCE trial.

BACKGROUND: The innate and adaptive immune system is involved in the airway inflammation associated with acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). We evaluated the association of mannose-binding lectin (MBL), immunoglobulin (Ig) and ficolin-2 concentrations with COPD exacerbations and according to the glucocorticoid treatment duration for an index exacerbation. METHODS: Post-hoc analysis of the randomized, double-blind, placebo-controlled REDUCE trial of 5 vs. 14 days of glucocorticoid treatment for an index exacerbation. MBL, ficolin-2 and total IgG/IgA and subclass concentrations were determined in stored samples drawn (n = 178) 30 days after the index exacerbation and associated with the risk of re-exacerbation during a 180-day follow-up period. RESULTS: IgG and subclass concentrations were significantly lower after 14 days vs. 5 days of glucocorticoid treatment. Patients with higher MBL concentrations were more likely to suffer from a future exacerbation (multivariable hazard ratio 1.03 per 200 ng/ml increase (95% confidence interval (CI) 1.00-1.06), p = 0.048), whereas ficolin-2 and IgG deficiency were not associated. The risk was most pronounced in patients with high MBL concentrations, IgG deficiency and 14 days of glucocorticoid treatment pointing towards an interactive effect of MBL and IgG deficiency in the presence of prolonged glucocorticoid treatment duration [Relative excess risk due to interaction 2.13 (95% CI - 0.41-4.66, p = 0.10)]. IgG concentrations were significantly lower in patients with frequent re-exacerbations (IgG, 7.81 g/L vs. 9.53 g/L, p = 0.03). CONCLUSIONS: MBL modified the short-term exacerbation risk after a recent acute exacerbation of COPD, particularly in the setting of concurrent IgG deficiency and recent prolonged systemic glucocorticoid treatment. Ficolin-2 did not emerge as a predictor of a future exacerbation risk.

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.

Effect of different corticosteroid regimes for hospitalised patients with exacerbated COPD: pooled analysis of individual participant data from the REDUCE and CORTICO-COP trials.

BACKGROUND: Systemic corticosteroid administration for severe acute exacerbations of COPD (AECOPD) reduces the duration of hospital stays. Corticosteroid-sparing regimens have showed non-inferiority to higher accumulated dose regimens regarding re-exacerbation risk in patients with AECOPD. However, it remains unclear whether 14-day or 2-5-day regimens would result in shorter admission durations and changes in mortality risk. We explored this by analysing the number of days alive and out of hospital based on two randomised controlled trials with different corticosteroid regimens. METHODS: We pooled individual patient data from the two available multicentre randomised trials on corticosteroid-sparing regimens for AECOPD: the REDUCE (n = 314) and CORTICO-COP (n = 318) trials. In the 14-day regimen group, patients were older, fewer patients received pre-treatment with antibiotics and more patients received pre-treatment with systemic corticosteroids. Patients randomly allocated to the 14-day and 2-5-day regimens were compared, with adjustment for baseline differences. RESULTS: The number of days alive and out of hospital within 14 days from recruitment was higher for the 2-5 day regimen group (mean 8.4 days; 95% confidence interval [CI] 8.0-8.8) than the 14-day regimen patient group (4.2 days; 95% CI3.4-4.9; p < 0.001). The 14-day AECOPD group had longer hospital stays (mean difference, 5.4 days [standard error ± 0.6]; p < 0.0001) and decreased likelihood of discharge within 30 days (hazard ratio [HR] 0.5; 95% CI 0.4-0.6; p < 0.0001). Comparing the 14-day regimen and the 2-5 day regimen group showed no differences in the composite endpoint 'death or ICU admission' (odds ratio [OR] 1.4; 95% CI 0.8-2.3; p = 0.15), new or aggravated hypertension (OR 1.5; 95% CI 0.9-2.7; p = 0.15), or mortality risk (HR 0.8; 95% CI 0.4-1.5; p = 0.45) during the 6-month follow-up period. CONCLUSION: 14-day corticosteroid regimens were associated with longer hospital stays and fewer days alive and out of hospital within 14 days, with no apparent 6-month benefit regarding death or admission to ICU in COPD patients. Our results favour 2-5 day regimens for treating COPD exacerbations. However, prospective studies are needed to validate these findings.

Does mid-regional pro-adrenomedullin (MR-proADM) improve the sequential organ failure assessment-score (SOFA score) for mortality-prediction in patients with acute infections? Results of a prospective observational study.

OBJECTIVES: Risk stratification in patients with infection is usually based on the Sequential Organ Failure Assessment-Score (SOFA score). Our aim was to investigate whether the vasoactive peptide mid-regional pro-adrenomedullin (MR-proADM) improves the predictive value of the SOFA score for 30-day mortality in patients with acute infection presenting to the emergency department (ED). METHODS: This secondary analysis of the prospective observational TRIAGE study included 657 patients with infection. The SOFA score, MR-proADM, and traditional inflammation markers were all measured at time of admission. Associations of admission parameters and 30-day mortality were investigated by measures of logistic regression, discrimination analyses, net reclassification index (NRI), and integrated discrimination index (IDI). RESULTS: MR-proADM values were higher in non-survivors compared with survivors (4.5±3.5 nmol/L vs. 1.7 ± 1.8 nmol/L) with an adjusted odds ratio of 26.6 (95% CI 3.92 to 180.61, p=0.001) per 1 nmol/L increase in admission MR-proADM levels and an area under the receiver operator curve (AUC) of 0.86. While the SOFA score alone revealed an AUC of 0.81, adding MR-proADM further improved discrimination (AUC 0.87) and classification within predefined risk categories (NRI 0.075, p-value <0.05). An admission MR-proADM threshold of 1.75 nmol/L provided the best prognostic accuracy for 30-day mortality; with a sensitivity of 81% and a specificity of 75%, and a negative predictive value of 98%. CONCLUSIONS: MR-proADM improved the mortality risk stratification in patients with infection presenting to the ED beyond SOFA score alone and may further improve initial therapeutic site-of-care decisions. TRIAL REGISTRATION: ClinicalTrials.gov NCT01768494. Registered January 15, 2013.

The vasoactive peptide MR-pro-adrenomedullin in COVID-19 patients: an observational study.

OBJECTIVES: Midregional pro-adrenomedullin (MR-proADM) is a vasoactive peptide with key roles in reducing vascular hyperpermeability and thereby improving endothelial stability during infection. While MR-proADM is useful for risk stratification in patients with sepsis, clinical data about prediction accuracy in patients with severe acute respiratory syndrome coronavirus 2 disease (COVID-19) is currently missing. METHODS: We included consecutively adult patients hospitalized for confirmed COVID-19 at a tertiary care center in Switzerland between February and April 2020. We investigated the association of MR-proADM levels with in-hospital mortality in logistic regression and discrimination analyses. RESULTS: Of 89 included COVID-19 patients, 19% (n=17) died while in the hospital. Median admission MR-proADM levels (nmol/L) were increased almost 1.5-fold increased in non-survivors compared to survivors (1.3 [interquartile range IQR 1.1-2.3]) vs. 0.8 [IQR 0.7-1.1]) and showed good discrimination (area under the curve 0.78). An increase of 1 nmol/L of admission MR-proADM was independently associated with a more than fivefold increase in in-hospital mortality (adjusted odds ratio of 5.5, 95% confidence interval 1.4-21.4, p=0.015). An admission MR-proADM threshold of 0.93 nmol/L showed the best prognostic accuracy for in-hospital mortality with a sensitivity of 93%, a specificity of 60% and a negative predictive value of 97%. Kinetics of follow-up MR-proADM provided further prognostic information for in-hospital treatment. CONCLUSIONS: Increased levels of MR-proADM on admission and during hospital stay were independently associated with in-hospital mortality and may allow a better risk stratification, and particularly rule-out of fatal outcome, in COVID-19 patients.

Duration of antibiotic treatment using procalcitonin-guided treatment algorithms in older patients: a patient-level meta-analysis from randomized controlled trials.

BACKGROUND: Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients. OBJECTIVE AND DESIGN: We performed an individual patient data meta-analysis to investigate the association of age on effects of PCT-guided antibiotic stewardship regarding antibiotic use and outcome. SUBJECTS AND METHODS: We had access to 9,421 individual infection patients from 28 randomized controlled trials comparing PCT-guided antibiotic therapy (intervention group) or standard care. We stratified patients according to age in four groups (<75 years [n = 7,079], 75-80 years [n = 1,034], 81-85 years [n = 803] and >85 years [n = 505]). The primary endpoint was the duration of antibiotic treatment and the secondary endpoints were 30-day mortality and length of stay. RESULTS: Compared to control patients, mean duration of antibiotic therapy in PCT-guided patients was significantly reduced by 24, 22, 26 and 24% in the four age groups corresponding to adjusted differences in antibiotic days of -1.99 (95% confidence interval [CI] -2.36 to -1.62), -1.98 (95% CI -2.94 to -1.02), -2.20 (95% CI -3.15 to -1.25) and - 2.10 (95% CI -3.29 to -0.91) with no differences among age groups. There was no increase in the risk for mortality in any of the age groups. Effects were similar in subgroups by infection type, blood culture result and clinical setting (P interaction >0.05). CONCLUSIONS: This large individual patient data meta-analysis confirms that, similar to younger patients, PCT-guided antibiotic treatment in older patients is associated with significantly reduced antibiotic exposures and no increase in mortality.

Quality of life after hospitalization predicts one-year readmission risk in a large Swiss cohort of medical in-patients.

PURPOSE: Estimating the probability of readmission following hospitalization using prediction scores can be complex. Quality of life (QoL) may provide an easy and effective alternative. METHODS: Secondary analysis of the prospective "TRIAGE" cohort. All medical in-patients admitted to a Swiss tertiary care institution (2016-2019) ≥18 years with a length of stay of ≥2 days (23,309 patients) were included. EQ-5D VAS, EQ-5D index, and Barthel index were assessed at a single telephone interview 30-day after admission. Patients lost to follow-up were excluded. Readmission was defined as a non-elective hospital stay at our institution >24 h within 1 year after discharge and assessed using area under the curve (AUC) analysis with adjustment for confounders. RESULTS: 12,842 patients (43% females, median age 68, IQR 55-78) were included. Unadjusted discrimination was modest at 0.59 (95% CI 0.56-0.62) for EQ-5D VAS. Partially adjusted discrimination (for gender) was identical. Additional adjustment for insurance, Charlson comorbidity index, length of stay, and native language increased the AUC to 0.66 (95% CI 0.63-0.69). Results were robust irrespective of time to event (12, 6 or 3 months). A cut-off in the unadjusted model of EQ-5D VAS of 55 could separate cases with a specificity of 80% and a sensitivity of 30%. CONCLUSION: QoL at day 30 after admission can predict one-year readmission risk with similar precision as more intricate tools. It might help for identification of high-risk patients and the design of tailored prevention strategies.

Selective resection of cushing microadenoma guided by preoperative hybrid 18-fluoroethyl-L-tyrosine and 11-C-methionine PET/MRI.

PURPOSE: 11-C-methionine (MET)-positron emission tomography (PET) as an adjunct to magnetic resonance imaging (MRI) has been proposed as a suitable molecular imaging modality for localizing pituitary adenomas in Cushing's disease. 18-F-Fluoroethyl-L-tyrosine (FET)-PET, which is more widely available has not yet been reported in this context. METHODS: Retrospective double-center cohort study on 15 patients who underwent transsphenoidal surgery for biochemically proven Cushing's disease between 2011 and 2019. Preoperative MET-PET/MRI and/or FET-PET/MRI were compared with intraoperative and histopathological examinations using the Mann Whitney U test and the Fisher's Exact test, along with positive predictive value calculations. RESULTS: Fifteen patients were included, with a mean age of 47.2 (18-69) years. Six patients received either a MET-PET/MRI or a FET-PET/MRI and 3 patients both exams, respectively. 67% of the tumors were detected by MRI (MET-PET-group [56%]; FET-PET-group [78%]). All tumors were microadenomas with a mean adenoma volume of 0.19 cm3 (0.02-0.78), all of which displayed a circumscribed pathological FET- and/or MET-uptake. FET-PET/MRI results positively correlated with the localization of the tumor confirmed intraoperatively and histopathologically in all cases, resulting in a sensitivity and specificity of FET-PET/MRI for tumor localization of 100% (95% CI 66.37-100%). One MET-PET/MRI suggested a localization contralateral to the expected spot. The sensitivity and specificity of MET-PET for tumor localization hence was 89% (95% CI 51.75-99.72%). CONCLUSIONS: Preoperative hybrid FET-PET/MRI and MET-PET/MRI have a high predictive value in localizing corticotroph adenoma for selective adenomectomy in Cushing's disease.

Adrenal function testing in dialysis patients - a review of the literature.

BACKGROUND: Secondary adrenal insufficiency is a frequent issue in patients with renal replacement therapy. There are concerns about metabolism and clearance for adrenocorticotropic hormone (ACTH) and cortisol in addition to hemoconcentration as confounding factors during hemodialysis (HD). Therefore, ACTH testing is currently performed before or in between HD sessions. This review of the literature aims to evaluate the current evidence for validity of testing for adrenal insufficiency in patients on chronic renal replacement therapy. METHODS: A literature search of PubMed database for interventional and observational clinical trials was performed. Case reports and reviews were excluded. The search included all articles published until July 2020. RESULTS: Of 218 potentially eligible articles, 16 studies involving 381 participants were included. Seven studies performed an ACTH test before HD or in between HD sessions. There was no data available regarding ACTH testing during HD. But there was evidence of decreased cortisol levels during HD as compared to afterwards. All included 16 studies measured basal cortisol, and seven studies performed an ACTH test. Seven trials had comparable data of baseline cortisol for a quantitative analysis. Standardized mean difference of overall cortisol was 0.18 nmol/l (95%CI - 0.08 to 0.44) in the case group. CONCLUSIONS: In patients undergoing renal replacement therapy, basal serum cortisol values are comparable to healthy volunteers. There is limited data on the validity of stimulated cortisol in these patients, especially during HD. TRIAL REGISTRATION: Registration no. CRD42020199245 .

Prevalence and outcome of comorbidities associated with acromegaly.

BACKGROUND: Acromegaly is associated with various comorbidities, such as arterial hypertension (aHT), type 2 diabetes mellitus (DM2), obstructive sleep apnoea syndrome (OSAS), carpal tunnel syndrome (CTS) and polyposis coli. For therapeutic decisions, it is essential to know if, and to what extent, these associated morbidities are reversible or preventable. The aim of this study is to assess the prevalence and course of aHT, obesity, OSAS, CTS, DM2 and polyposis coli in acromegalic patients. METHODS: The following criteria for inclusion in this database study were used: treatment for acromegaly at the authors' institutions; full endocrinological and radiological work- and follow-up; screening for aHT, DM2, CTS, OSAS, obesity and polyposis coli. All patients were followed-up for > 3 months, and treatments were indicated with the intent of biochemical remission (normal IGF-1 and random growth hormone level). RESULTS: Sixty-three patients were included. Twelve (19%), 45 (71%) and 6 (10%) patients harboured micro-, macro- and giant adenomas, respectively. Nineteen tumours (30%) invaded the cavernous sinus. Mean tumour volume was 5.4 cm3. Mean follow-up time was 42 months. Sixty-one (97%) patients had transsphenoidal surgery; two patients only had drug therapy. Surgery led to remission in 31 (51%) patients. Intracavernous growth and larger tumour volume were negative predictors for cure. Drug therapy lead to remission in 22 (73%) patients within a mean follow-up of 54 months. The pretherapeutic prevalence of associated morbidities was as follows: aHT, 56%; DM2, 25%; OSAS, 29%; CTS, 29%; polyposis coli, 5%. There were neither age nor gender preferences for the respective prevalences. Surgery leads to remission of aHT and DM2 in 6% and 25%, respectively. Additional drug therapy resulted in remission of aHT, DM2 and CTS in 17%, 14% and 14%, respectively. Other associated morbidities persisted regardless of therapeutic efforts. Even if criteria for remission were not met, no new comorbidities of acromegaly developed during follow-up. CONCLUSIONS: Treating acromegaly may relieve threatening associated morbidities such as aHT and DM2; nevertheless, only few comorbidities are reversible, which highlights the importance of treating acromegaly as early as possible.

The Shape grading system: a classification for growth patterns of pituitary adenomas.

BACKGROUND: Long-term tumor control of pituitary adenomas may be achieved by gross total resection (GTR). Factors, which influence the extent of resection, are invasiveness, tumor size, and possibly tumor shape. Nevertheless, the latter factor has not been assessed so far and there is no classification for the different shapes. The aim of this study was to evaluate the impact of different tumor shapes on GTR rates and outcome according to our proposed "Shape grading system." METHODS: In this retrospective single center study, the radiological outcome of nonfunctioning pituitary adenomas was assessed with respect to the following previously defined growth patterns: spherical (Shape I), oval (Shape II), dumbbell (Shape III), mushroom (Shape IV), and polylobulated (Shape V). RESULTS: A total of 191 patients were included (Shape I, n = 28 (15%); Shape II, n = 91 (48%); Shape III, n = 37 (19%); Shape IV, n = 12 (6%); Shape V, n = 23 (12%)). GTR was achieved in 101 patients (53%) with decreasing likelihood of GTR in higher shape grades (Shape I, n = 23 (82%); Shape II, n = 67 (74%); Shape III, n = 9 (24%); Shape IV, n = 2 (17%); Shape V, n = 0 (0%)). This correlated with larger tumor remnants, a higher risk of tumor recurrence/regrowth and therefore necessity of re-surgery and/or radiotherapy/radiosurgery. CONCLUSION: The "Shape grading system" may be used as a predictor of the outcome in nonfunctioning pituitary adenomas. The higher the "Shape grade," the higher the likelihood for lower GTR rates, larger tumor remnants, and need for further therapies.

Individualised nutritional support in medical inpatients at nutritional risk: a randomised clinical trial.

BACKGROUND: Guidelines recommend the use of nutritional support during hospital stays for medical patients (patients not critically ill and not undergoing surgical procedures) at risk of malnutrition. However, the supporting evidence for this recommendation is insufficient, and there is growing concern about the possible negative effects of nutritional therapy during acute illness on recovery and clinical outcomes. Our aim was thus to test the hypothesis that protocol-guided individualised nutritional support to reach protein and caloric goals reduces the risk of adverse clinical outcomes in medical inpatients at nutritional risk. METHODS: The Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) is a pragmatic, investigator-initiated, open-label, multicentre study. We recruited medical patients at nutritional risk (nutritional risk screening 2002 [NRS 2002] score ≥3 points) and with an expected length of hospital stay of more than 4 days from eight Swiss hospitals. These participants were randomly assigned (1:1) to receive either protocol-guided individualised nutritional support to reach protein and caloric goals (intervention group) or standard hospital food (control group). Randomisation was done with variable block sizes and stratification according to study site and severity of malnutrition using an interactive web-response system. In the intervention group, individualised nutritional support goals were defined by specialist dietitians and nutritional support was initiated no later than 48 h after admission. Patients in the control group received no dietary consultation. The composite primary endpoint was any adverse clinical outcome defined as all-cause mortality, admission to intensive care, non-elective hospital readmission, major complications, and decline in functional status at 30 days, and it was measured in all randomised patients who completed the trial. This trial is registered with ClinicalTrials.gov, number NCT02517476. FINDINGS: 5015 patients were screened, and 2088 were recruited and monitored between April 1, 2014, and Feb 28, 2018. 1050 patients were assigned to the intervention group and 1038 to the control group. 60 patients withdrew consent during the course of the trial (35 in the intervention group and 25 in the control group). During the hospital stay, caloric goals were reached in 800 (79%) and protein goals in 770 (76%) of 1015 patients in the intervention group. By 30 days, 232 (23%) patients in the intervention group experienced an adverse clinical outcome, compared with 272 (27%) of 1013 patients in the control group (adjusted odds ratio [OR] 0·79 [95% CI 0·64-0·97], p=0·023). By day 30, 73 [7%] patients had died in the intervention group compared with 100 [10%] patients in the control group (adjusted OR 0·65 [0·47-0·91], p=0·011). There was no difference in the proportion of patients who experienced side-effects from nutritional support between the intervention and the control group (162 [16%] vs 145 [14%], adjusted OR 1·16 [0·90-1·51], p=0·26). INTERPRETATION: In medical inpatients at nutritional risk, the use of individualised nutritional support during the hospital stay improved important clinical outcomes, including survival, compared with standard hospital food. These findings strongly support the concept of systematically screening medical inpatients on hospital admission regarding nutritional risk, independent of their medical condition, followed by a nutritional assessment and introduction of individualised nutritional support in patients at risk. FUNDING: The Swiss National Science Foundation and the Research Council of the Kantonsspital Aarau, Switzerland.

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.