Subacute Thyroiditis Complicating COVID-19 Infection.

Subacute thyroiditis (SAT) is a self-limited inflammatory disease and a rare cause of thyrotoxicosis. Although the exact etiology of SAT is not sufficiently understood, it is generally associated to viral infections. Current evidence highlights that SAT may be a potentially uncommon manifestation of ongoing Coronavirus disease 2019 (COVID-19) infection or a post-viral complication of the disease. Despite that SAT is a rare manifestation associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease both in ongoing and resolved COVID-19 infection, the ever-increasing numbers of COVID-19 patients strengthens the possibility that this particular disease entity will be of more immediate concern in the future. The current work aims to summarize the approach of SARS-CoV-2-associated SAT, present its pathophysiology, outline current research evidence found in the literature, and discuss potential differential diagnoses and diagnostic dilemmas through an illustrative case.

Refeeding Syndrome: A Critical Reality in Patients with Chronic Disease.

Malnutrition is one of the most frequent metabolic challenges in the population of chronically ill patients. This results in increased administration of nutritional therapy in inpatient settings, which poses the risk of side effects, in particular, the development of refeeding syndrome. If not managed accordingly, it leads to a significant rise in morbidity and mortality. However, despite its importance, evidence-based recommendations on the management of refeeding syndrome are largely lacking, and only a few randomized controlled trials have been conducted. In light of this, the aim of this review is to raise awareness of refeeding syndrome in chronically ill patients by critically reviewing recent literature and providing a short overview as well as diagnosis and treatment algorithms of this underreported metabolic condition. In summary, recent findings suggest undergoing risk assessment and stratification for every patient receiving nutritional therapy. According to this, adaptation of energy and fluid support during the replenishment phase should be implemented in the nutritional therapy for patients at high risk. Additionally, continuous monitoring should take place, and appropriate actions should be initiated when necessary.

Refeeding syndrome: update and clinical advice for prevention, diagnosis and treatment.

PURPOSE OF REVIEW: The aim of this review is to provide a brief overview of the refeeding syndrome, to discuss more recent advice on diagnosis and treatment, and to raise awareness of this still poorly understood metabolic condition. RECENT FINDINGS: To date, evidence regarding the refeeding syndrome has been very limited. A number of reviews and case reports exist, but only a few are randomized trials. Recently, it has been shown that the vast majority of physicians are unaware of this metabolic condition. Precise guidelines for diagnosis and treatment of this syndrome were lacking for a long time. Now, a consensus statement is available, providing guidance from experts in the field on the management of patients at increased risk of refeeding syndrome (RFS) receiving nutritional therapy. SUMMARY: Due to the increased use of nutritional therapy in inpatient settings, physicians should be aware of possible side effects, particularly in connection with the refeeding syndrome. In this context, every patient should undergo a risk assessment for refeeding syndrome and stratification before starting nutritional therapy. For patients at high risk, nutritional support should be administered with adapted energy and fluid support during the replenishment phase. In addition, the occurrence of RFS during nutritional therapy must be continuously evaluated, and appropriate steps taken if necessary.

Refeeding syndrome is associated with increased mortality in malnourished medical inpatients: Secondary analysis of a randomized trial.

BACKGROUND: Whether the occurrence of refeeding syndrome (RFS), a metabolic condition characterized by electrolyte shifts after initiation of nutritional therapy, has a negative impact on clinical outcomes remains ill-defined. We prospectively investigated a subgroup of patients included in a multicentre, nutritional trial (EFFORT) for the occurrence of RFS. METHODS: In this secondary analysis of a randomized-controlled trial investigating the effects of nutritional support in malnourished medical inpatients, we prospectively screened patients for RFS and classified them as "RFS confirmed" and "RFS not confirmed" based on predefined criteria (i.e. electrolyte shifts, clinical symptoms, clinical context, and patient history). We assessed associations of RFS and mortality within 180 days (primary endpoint) and other secondary endpoints using multivariable regression analysis. RESULTS: Among 967 included patients, RFS was confirmed in 141 (14.6%) patients. Compared to patients with no evidence for RFS, patients with confirmed RFS had significantly increased 180-days mortality rates (42/141 (29.8%) vs 181/826 (21.9%), adjusted odds ratio (OR) 1.53 (95% CI 1.02 to 2.29), P < .05). Patients with RFS also had an increased risk for ICU admission (6/141 (4.3%) vs 13/826 (1.6%), adjusted OR 2.71 (95% CI 1.01 to 7.27), P < .05) and longer mean length of hospital stays (10.5 ±â€Š6.9 vs 9.0 ±â€Š6.6 days, adjusted difference 1.57 days (95% CI 0.38-2.75), P = .01). CONCLUSION: A relevant proportion of medical inpatients with malnutrition develop features of RFS upon hospital admission, which is associated with long-term mortality and other adverse clinical outcomes. Further studies are needed to develop preventive strategies for RFS in this patient population.

Effects of procalcitonin testing on antibiotic use and clinical outcomes in patients with upper respiratory tract infections. An individual patient data meta-analysis.

BACKGROUND: Several trials found procalcitonin (PCT) helpful for guiding antibiotic treatment in patients with lower respiratory tract infections and sepsis. We aimed to perform an individual patient data meta-analysis on the effects of PCT guided antibiotic therapy in upper respiratory tract infections (URTI). METHODS: A comprehensive search of the literature was conducted using PubMed (MEDLINE) and Cochrane Library to identify relevant studies published until September 2016. We reanalysed individual data of adult URTI patients with a clinical diagnosis of URTI. Data of two trials were used based on PRISMA-IPD guidelines. Safety outcomes were (1) treatment failure defined as death, hospitalization, ARI-specific complications, recurrent or worsening infection at 28 days follow-up; and (2) restricted activity within a 14-day follow-up. Secondary endpoints were initiation of antibiotic therapy, and total days of antibiotic exposure. RESULTS: In total, 644 patients with a follow up of 28 days had a final diagnosis of URTI and were thus included in this analysis. There was no difference in treatment failure (33.1% vs. 34.0%, OR 1.0, 95% CI 0.7-1.4; p=0.896) and days with restricted activity between groups (8.0 vs. 8.0 days, regression coefficient 0.2 (95% CI -0.4 to 0.9), p=0.465). However, PCT guided antibiotic therapy resulted in lower antibiotic prescription (17.8% vs. 51.0%, OR 0.2, 95% CI 0.1-0.3; p<0.001) and in a 2.4 day (95% CI -2.9 to -1.9; p<0.001) shorter antibiotic exposure compared to control patients. CONCLUSIONS: PCT guided antibiotic therapy in the primary care setting was associated with reduced antibiotic exposure in URTI patients without compromising outcomes.

Pro-Adrenomedullin predicts 10-year all-cause mortality in community-dwelling patients: a prospective cohort study.

BACKGROUND: Several studies found mid-regional pro-adrenomedullin (ProADM), the prohormone of the cardiovascular protein adrenomedullin, to be strongly associated with short-term mortality, mostly in the inpatient setting. We evaluated associations of ProADM levels with 10-year mortality in community-dwelling primary care patients with respiratory tract infections. METHODS: This is a post-hoc analysis using clinical and biomarker data of 134 primary care patients with respiratory tract infections. ProADM was measured on admission and after 7 days in batch-analysis. 10-year follow-up data was collected by GP, patient and relative tracing through phone interviews. We calculated Cox regression models and area under the receiver operating characteristics curves to assess associations of ProADM with 10-year all-cause mortality. RESULTS: During the 10-year follow-up 6% of included patients died. Median baseline ProADM blood levels (nmol/l) were significantly higher in non-survivors compared to survivors (0.5, IQR 0.4-1.3; vs. 0.2, IQR 0.1-0.5; p = 0.02) and showed a significant association with 10-year all-cause mortality in an age-adjusted cox regression model (HR: 2.5, 95%-CI: 1.0-6.1, p = 0.04). ProADM levels on day 7 showed similar results. CONCLUSIONS: This posthoc analysis found an association of elevated ProADM blood levels and 10-year all-cause mortality in a primary care cohort with respiratory tract infections. Due to the methodological limitations including incomplete data regarding follow-up information and biomarker measurement, this study warrants validation in future larger studies. TRIAL REGISTRATION: Current Controlled Trials, SRCTN73182671.

The natriuretic peptide MR-proANP predicts all-cause mortality and adverse outcome in community patients: a 10-year follow-up study.

BACKGROUND: The precursor peptide of atrial natriuretic peptide (MR-proANP) has a physiological role in fluid homeostasis and is associated with mortality and adverse clinical outcomes in heart failure patients. Little is known about the prognostic potential of this peptide for long-term mortality prediction in community-dwelling patients. We evaluated associations of MR-proANP levels with 10-year all-cause mortality in patients visiting their general practitioner for a respiratory tract infection. METHODS: In this post-hoc analysis including 359 patients (78.5%) of the original trial, we calculated cox regression models and area under the receiver operating characteristic curve (AUC) to assess associations of MR-proANP blood levels with mortality and adverse outcome including death, pulmonary embolism, and major adverse cardiac or cerebrovascular events. RESULTS: After a median follow-up of 10.0 years, 9.8% of included patients died. Median admission MR-proANP levels were significantly elevated in non-survivors compared to survivors (80.5 pmol/L, IQR 58.6-126.0; vs. 45.6 pmol/L, IQR 34.2-68.3; p<0.001) and associated with 10-year all-cause mortality (age-adjusted HR 2.0 [95% CI 1.3-3.1, p=0.002]; AUC 0.79). Results were similar for day 7 blood levels and also for the prediction of other adverse outcomes. CONCLUSIONS: Increased MR-proANP levels were associated with 10-year all-cause mortality and adverse clinical outcome in a sample of community-dwelling patients. If diagnosis-specific cut-offs are confirmed in future studies, this marker may help to direct preventive measures in primary care.

Trimethylamine-N-oxide (TMAO) predicts fatal outcomes in community-acquired pneumonia patients without evident coronary artery disease.

INTRODUCTION: The pro-atherosclerotic metabolite trimethylamine-N-oxide (TMAO) is a risk factor for incident cardiovascular events and a potentially modifiable mediator of chronic inflammation through broad-spectrum antibiotic treatment by changing the microbiome. Whether TMAO is associated with adverse clinical outcomes in acute inflammatory community-acquired pneumonia (CAP) patients is unknown. METHODS: A total of 317 CAP patients from a previous Swiss multicenter trial were prospectively followed for a median of 6.1years. TMAO plasma levels were measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We used Cox regression models to investigate associations between baseline TMAO levels and all-cause mortality. RESULTS: Six-year mortality was 45.1%, and 18.9% of the patients had coronary artery disease (CAD). Median admission TMAO (µmolL-1) levels were significantly higher in non-survivors compared to survivors (4.1 [interquartile range (IQR), 2.2-7.2] vs. 2.5 [IQR, 1.5-4.1]; p<0.001). A strong association between TMAO and 6-year all-cause mortality was found for patients without CAD (adjusted hazard ratio (HR) 1.9 ([95% CI 1.2-3.1]; p<0.05). In patients with known CAD, no such association was found (adjusted HR 0.6 (0.2-1.6); p=0.309, interaction p=0.009). In patients without antibiotic pretreatment receiving antibiotic treatment, TMAO significantly decreased from admission to day seven (median, 3.9 [IQR, 2.1-7.5] vs. 3.1 [IQR, 1.4-6.6]; p<0.01). CONCLUSIONS: TMAO is associated with long-term fatal outcomes in CAP patients without evident CAD and modifiable through antibiotic treatment. Whether chronic modulation of TMAO by targeting the microbiome reduces mortality risk needs to be evaluated in future interventional trials.

Copeptin predicts 10-year all-cause mortality in community patients: a 10-year prospective cohort study.

BACKGROUND: Copeptin, the C-terminal part of the arginine vasopressin (AVP) precursor peptide, is secreted in response to stress and correlates with adverse clinical outcomes in the acute-care hospital setting. There are no comprehensive data regarding its prognostic value in the community. We evaluated associations of copeptin levels with 10-year mortality in patients visiting their general practitioner (GP) for a respiratory infection included in a previous trial. METHODS: This is a post hoc analysis including data from 359 patients included in the PARTI trial. Copeptin was measured in batch-analysis on admission and after 7 days. We calculated Cox regression models and area under the receiver operating characteristic curve (AUC) to assess an association of copeptin with mortality and adverse outcome. Follow-up data were collected by GP, patient and relative tracing through phone interviews 10 years after trial inclusion. RESULTS: After a median follow-up of 10.0 years, mortality was 9.8%. Median admission copeptin levels (pmol/L) were significantly elevated in non-survivors compared to survivors (13.8, IQR 5.9-27.8; vs. 6.3 IQR 4.1-11.5; p<0.001). Admission copeptin levels were associated with 10-year all-cause mortality [age-adjusted hazard ratio 1.7 (95% CI, 1.2-2.5); p<0.001, AUC 0.68]. Results were similar for discharge copeptin levels. Copeptin also predicted adverse outcomes defined as death, pulmonary embolism and major adverse cardiac and cerebrovascular events. CONCLUSIONS: In a sample of community-dwelling patients visiting their GP for a respiratory infection, copeptin levels were associated with 10-year all-cause mortality. In conjunction with traditional risk factors, this marker may help to better direct preventive measures in this population.

Extraocular light via the ear canal does not acutely affect human circadian physiology, alertness and psychomotor vigilance performance.

We aimed at testing potential effects of extraocular bright light via the ear canals on human evening melatonin levels, sleepiness and psychomotor vigilance performance. Twenty healthy young men and women (10/10) kept a regular sleep-wake cycle during the 2-week study. The volunteers reported to the laboratory on three evenings, 2 h 15 min before usual bedtime, on average at 21:45 h. They were exposed to three different light conditions, each lasting for 12 min: extraocular bright light via the ear canal, ocular bright light as an active control condition and a control condition (extraocular light therapy device with completely blacked out LEDs). The timing of exposure was on average from 22:48 to 23:00 h. During the 2-h protocol, saliva samples were collected in 15-min intervals for melatonin assays along with subjective sleepiness ratings, and the volunteers performed a 10-min visual psychomotor vigilance task (PVT) prior to and after each light condition. The evening melatonin rise was significantly attenuated after the 12-min ocular bright light exposure while no significant changes were observed after the extraocular bright light and sham light condition. Subjective sleepiness decreased immediately over a short period only after ocular light exposure. No significant differences were observed for mean reaction times and the number of lapses for the PVT between the three light conditions. We conclude that extraocular transcranial light exposure in the late evening does not suppress melatonin, reduce subjective sleepiness or improve performance, and therefore, does not acutely influence the human circadian timing system.