Triage tool for suspected COVID-19 patients in the emergency room: AIFELL score

Abstract Clinical prediction scores support the assessment of patients in the emergency setting to determine the need for further diagnostic and therapeutic steps. During the current COVID-19 pandemic, physicians in emergency rooms (ER) of many hospitals have a considerably higher patient load and need to decide within a short time frame whom to hospitalize. Based on our clinical experiences in dealing with COVID-19 patients at the University Hospital in Zurich, we created a triage score with the acronym "AIFELL" consisting of clinical, radiological and laboratory findings.The score was then evaluated in a retrospective analysis of 122 consecutive patients with suspected COVID-19 from March until mid-April 2020. Descriptive statistics, Student's t-test, ANOVA and Scheffe's post-hoc analysis confirmed the diagnostic power of the score. The results suggest that the AIFELL score has potential as a triage tool in the ER setting intended to select probable COVID-19 cases for hospitalization in spontaneously presenting or referred patients with acute respiratory symptoms.

Risk Factors of In-Hospital Mortality in Patients Treated for Pneumonia at a Tertiary Care Centre in Switzerland.

BACKGROUND: Little is known about risk factors upon hospital admission that are associated with in-hospital death of patients hospitalized for bacterial pneumonia. Identifying such factors may help to optimize the treatment and lower the mortality of these patients. OBJECTIVES: The aim of the study was to characterize baseline characteristics of patients hospitalized for bacterial pneumonia in Switzerland and to identify risk factors associated with all-cause in-hospital mortality. METHODS: Routinely collected electronic health record data of patients discharged from a large Swiss tertiary care hospital between August 2009 and 2017 were analysed. Potential risk factors such as patient demographics, physical examination findings, vital signs, laboratory results, and comorbidities were considered within ±24 h of admission. Univariable and multivariable logistic regression models identified risk factors for in-hospital death. The area under the receiver operating characteristic (ROC) curve was used to compare the identified factors to existing pneumonia scoring systems. RESULTS: Out of 1,781 hospital stays with initial and main diagnosis of bacterial pneumonia, 85 patients (4.85%) died (33.9% female, median age 62.3 years [interquartile range, 52-75]). Age, low systolic blood pressure, underweight, a missing value for body mass index, decreased haemoglobin level, raised C-reactive protein, high urea, high lactate dehydrogenase, concomitant pleural effusion, and cancer were independently associated with in-hospital death. The area under the ROC curve was 0.89 for the multivariable model containing the identified predictors. CONCLUSIONS: Our data are consistent with previous trials characterizing patients hospitalized for pneumonia. Additionally, we identified new and independent risk factors associated with in-hospital death among patients treated for bacterial pneumonia. Findings need to be further validated in larger multicentre cohorts.

Swiss Delphi study on iron deficiency.

AIMS OF THE STUDY: Iron deficiency (ID) and iron deficiency anaemia (IDA) are important conditions affecting a large proportion of the general population, causing the patients physical and psychosomatic symptoms, particularly fatigue, and significantly affecting their quality of life. General practitioners (GPs) are frequently consulted with nonspecific symptoms due to the ID. However, little evidence is available to guide iron treatment. The aim of the Swiss Delphi study was to generate a broad consensual Swiss expert opinion in various therapeutic areas on diagnosis and treatment of ID/IDA and their practical implications. METHODS: Specific statements regarding clinical relevance, practical diagnostic and therapeutic approaches, and treatment were evaluated by Swiss experts in various therapeutic areas using the Delphi method. “Consensus” was defined as ≥80% agreement; the agreement of 50–79% was defined as “critical”, of <50% as “disagreement”. RESULTS: Consensus was reached for most statements. In patients without systemic inflammation, the threshold of 30 μg/l provide a good accuracy for the diagnosis of ID without anaemia. Ferritin levels within the range 30–50 μg/l with TSAT <20% can indicate ID without anaemia. Iron replacement therapy is accepted for treatment, not only of IDA, but also of symptomatic ID without anaemia. GPs play a central role in diagnosis and management of ID. CONCLUSIONS: This consensus study provides potential therapeutic strategies for management of iron deficiency and is based on opinions of a high number of contributing specialists, providing their views from a wide range of clinical perspectives.  .

The Relevance of Vitamin and Iron Deficiency in Patients with Inflammatory Bowel Diseases in Patients of the Swiss IBD Cohort.

Background andAims: Vitamin and iron deficiencies are common in patients with inflammatory bowel disease (IBD) as a result of chronic intestinal inflammation, increase in demand, or dietary restrictions. Here, we assessed the frequency of complications in relation to deficiency of iron, folate acid, and vitamin B12 in patients enrolled in the nationwide Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). Methods: A total of 2666 patients were included in the study, 1558 with Crohn's disease (CD) and 1108 with ulcerative colitis (UC). Results: Iron deficiency anemia was detected in 19.6% of CD patients and 21.6% of UC patients. In CD patients low BMI and nonsmoker status were positively associated with anemia. In both CD and UC, malabsorption syndrome, defined as failure of the GI tract to absorb 1 or more substances from the diet, was found to be significantly associated with anemia (6.2% and 3.8%, respectively) and current steroid use (40% CD, 52.7% UC). In CD patients with ileal (31.7% vs 20%) and colonic (29.9% vs 25%) disease location folate deficiency was significantly higher than in patients with ileocolonic CD or upper GI involvement. In CD patients, vitamin B12 deficiency was associated with the onset of stenosis and intestinal surgery (42.9% vs 32.8% and 46% vs 33% for patients with versus without B12 deficiency). Conclusion: Our data indicate that due to frequent occurrence of deficiency states, regular monitoring and substitution of vitamins and iron are mandatory and may prevent long-term intestinal and extraintestinal complications in IBD patients.

Risk factors for gallstones and kidney stones in a cohort of patients with inflammatory bowel diseases.

BACKGROUND: Gallstones and kidney stones are known complications of inflammatory bowel diseases (IBD). Risk factors have been insufficiently studied and explanatory studies date back up to 30 years. It remains unclear, whether improved treatment options also influenced risk factors for these complications. OBJECTIVES: Identifying risk factors for gallstones and kidney stones in IBD patients. METHODS: Using data from the Swiss Inflammatory Bowel Disease Cohort Study we assessed associations of diseases characteristics with gallstones and kidney stones in univariate and multivariate logistic regression analyses. RESULTS: Out of 2323 IBD patients, 104 (7.8%) Crohn's disease (CD) and 38 (3.8%) ulcerative colitis (UC) patients were diagnosed with gallstones. Significant risk factors for gallstones were diagnosis of CD, age at diagnosis, disease activity and duration, NSAID intake, extra-intestinal manifestations and intestinal surgery. Kidney stones were described in 61 (4.6%) CD and 30 (3.0%) UC patients. Male gender, disease activity, intestinal surgery, NSAID usage and reduced physical activity were significant risk factors. Hospitalization was associated with gallstones and kidney stones. The presence of gallstones increased the risk for kidney stones (OR 4.87, p<0.001). CONCLUSION: The diagnosis of CD, intestinal surgery, prolonged NSAID use, disease activity and duration and bowel stenosis were significantly associated with cholecystonephrolithiasis in IBD.

Chronic Pain: How Challenging Are DDIs in the Analgesic Treatment of Inpatients with Multiple Chronic Conditions?

BACKGROUND: Chronic pain is common in multimorbid patients. However, little is known about the implications of chronic pain and analgesic treatment on multimorbid patients. This study aimed to assess chronic pain therapy with regard to the interaction potential in a sample of inpatients with multiple chronic conditions. METHODS AND FINDINGS: We conducted a retrospective study with all multimorbid inpatients aged ≥18 years admitted to the Department of Internal Medicine of University Hospital Zurich in 2011 (n = 1,039 patients). Data were extracted from the electronic health records and reviewed. We identified 433 hospitalizations of patients with chronic pain and analyzed their combinations of chronic conditions (multimorbidity). We then classified all analgesic prescriptions according to the World Health Organization (WHO) analgesic ladder. Furthermore, we used a Swiss drug-drug interactions knowledge base to identify potential interactions between opioids and other drug classes, in particular coanalgesics and other concomitant drugs. Chronic pain was present in 38% of patients with multimorbidity. On average, patients with chronic pain were aged 65.7 years and had a mean number of 6.6 diagnoses. Hypertension was the most common chronic condition. Chronic back pain was the most common painful condition. Almost 90% of patients were exposed to polypharmacotherapy. Of the chronic pain patients, 71.1% received opioids for moderate to severe pain, 43.4% received coanalgesics. We identified 3,186 potential drug-drug interactions, with 17% classified between analgesics (without coanalgesics). CONCLUSIONS: Analgesic drugs-related DDIs, in particular opioids, in multimorbid patients are often complex and difficult to assess by using DDI knowledge bases alone. Drug-multimorbidity interactions are not sufficiently investigated and understood. Today, the scientific literature is scarce for chronic pain in combination with multiple coexisting medical conditions and medication regimens. Our work may provide useful information to enable further investigations in multimorbidity research within the scope of potential interactions and chronic pain.

Assessing adherence to multiple medications and in daily life among patients with multimorbidity.

OBJECTIVE: Chronic conditions often require multiple medication intake. However, past research has focused on assessing overall adherence or adherence to a single index medication only. This study explored adherence measures for multiple medication intake, and in daily life, among patients with multiple chronic conditions (i.e. multimorbidity). DESIGN: Eighty-four patients with multimorbidity and multiple-medication regimens completed three monthly panel questionnaires. A randomly assigned subsample additionally completed a 30-day daily diary. MAIN OUTCOME MEASURE: The Non-Adherence Report; a brief self-report measure of adherence to each prescribed medication (NAR-M), and in daily life. We further assessed the Medication Adherence Report Scale (MARS), and a subsample of participants were randomised to electronic adherence monitoring. RESULTS: The NAR-M indicated M = 94.7% adherence at Time 1 (SD = 9.3%). The NAR-M was significantly correlated with the MARS (rt1 = .52, rt2 = .57, and rt3 = .65; p < .001), and in tendency with electronically assessed adherence (rt2 = .45, rt3 = .46, p < .10). Variance components analysis indicated that between-person differences accounted for 10.2% of the variance in NAR-M adherence rates, whereas 22.9% were attributable to medication by person interactions. CONCLUSION: This study highlights the importance and feasibility of studying adherence to multiple medications differentially, and in daily life. Future studies may use these measures to investigate within-person and between-medication differences in adherence.

Basal mTORC2 activity and expression of its components display diurnal variation in mouse perivascular adipose tissue.

In adipose tissue mTOR complex 2 (mTORC2) contributes to the regulation of glucose/lipid metabolism and inflammatory molecule expression. Both processes display diurnal variations during the course of the day. RICTOR and mSIN1 are unique and essential components of mTORC2, which is activated by growth factors including insulin. To assess whether mTORC2 components display diurnal variations, we analyzed steady state mRNA expression levels of Rictor, mSin1, and mTor in various adipose tissues during a 24 h period. Diurnally regulated expression of Rictor was detected in brown adipose tissues displaying highest mRNA expression levels at the beginning of the 12 h light period (zeitgeber time 2, ZT2). Gene expression patterns of mSin1 and mTor displayed a similar diurnal regulation as Rictor in PVAT while smaller changes were detected for these genes in aorta during the course of the day. Basal mTORC2 activity was measured by phosphorylation of protein kinase C (PKC) α at serine 657 was higher at ZT14 as compared with ZT2 in PVAT. In line, gene expression of inflammatory molecules nitric oxide synthase 2 and tumor necrosis factor α was lower at ZT 14 compared to ZT2. Our findings provide evidence for a diurnal regulation of expression of mTORC2 components and activity. Hence, mTORC2 is possibly an integral part of diurnally regulated signaling pathways in PVAT and possibly in other adipose tissues.

Determinants of diagnostic performance of 18F-FDG PET/CT in patients with fever of unknown origin.

OBJECTIVES: There is uncertainty about patient selection and the adequate timing at which fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) is indicated in the diagnostic work-up of fever of unknown origin (FUO). The aim of this study was to determine the diagnostic performance of F-FDG PET/CT in patients with FUO. METHODS: All consecutive patients who underwent F-FDG PET/CT at the University Hospital Zurich because of FUO between 2006 and 2012 were included in this retrospective, observational study. RESULTS: A total of 76 patients [70% men, median (interquartile range) age 60 (47-67) years] were included. F-FDG PET/CT showed characteristically increased F-FDG activity in 56 patients (74%), leading to confirmation of or change in the suspected cause of FUO in 57 and 17%, respectively. The final diagnosis after F-FDG PET/CT included infection (21%), malignancy (22%), noninfectious inflammatory disease (12%), others (5%), or an unknown cause (40%). The success rate, sensitivity, and specificity of F-FDG PET/CT were 60, 77, and 31%, respectively. Sensitivity was highest in patients with suspected malignancy (100%, 95% confidence interval 79-100%). Diagnostic performance was independent of the investigated variables other than suspected infection as a cause of FUO (odds ratio 0.1, 95% confidence interval 0.01-0.8, P=0.033). CONCLUSION: The diagnostic performance of F-FDG PET/CT was significantly higher in patients with suspected malignancy causing a FUO compared with suspected infection or noninfectious inflammatory disease. However, it was independent of the baseline characteristics and duration of fever. This supports the recommendation to perform F-FDG PET/CT early in the diagnostic work-up of FUO, which may shorten disease duration and lower health costs, particularly when infection or malignancy is suspected.

[Swiss recommendations for the check-up in the doctor's office]. / Schweizer Empfehlungen für den Check-up in der Arztpraxis.

Prevention and screening of diseases belong to the role of each primary care physician. Recommendations have been developed in the EviPrev programme, which brings together members of all five academic ambulatory general internal medicine centers in Switzerland (Lausanne, Bern, Geneva, Basel and Zürich). Several questions must be addressed before realising a prevention intervention: Do we have data demonstrating that early intervention or detection is effective? What are the efficacy and adverse effects of the intervention? What is the efficiency (cost-effectiveness) of the intervention? What are the patient's preferences concerning the intervention and its consequences? The recommendations aim at answering these questions independently, taking into account the Swiss context and integrating the patient's perspective in a shared decision-making encounter.

Endothelial Rictor is crucial for midgestational development and sustained and extensive FGF2-induced neovascularization in the adult.

To explore the general requirement of endothelial mTORC2 during embryonic and adolescent development, we knocked out the essential mTORC2 component Rictor in the mouse endothelium in the embryo, during adolescence and in endothelial cells in vitro. During embryonic development, Rictor knockout resulted in growth retardation and lethality around embryonic day 12. We detected reduced peripheral vascularization and delayed ossification of developing fingers, toes and vertebrae during this confined midgestational period. Rictor knockout did not affect viability, weight gain, and vascular development during further adolescence. However during this period, Rictor knockout prevented skin capillaries to gain larger and heterogeneously sized diameters and remodeling into tortuous vessels in response to FGF2. Rictor knockout strongly reduced extensive FGF2-induced neovascularization and prevented hemorrhage in FGF2-loaded matrigel plugs. Rictor knockout also disabled the formation of capillary-like networks by FGF2-stimulated mouse aortic endothelial cells in vitro. Low RICTOR expression was detected in quiescent, confluent mouse aortic endothelial cells, whereas high doses of FGF2 induced high RICTOR expression that was associated with strong mTORC2-specific protein kinase Cα and AKT phosphorylation. We demonstrate that the endothelial FGF-RICTOR axis is not required during endothelial quiescence, but crucial for midgestational development and sustained and extensive neovascularization in the adult.

Hypoxia potentiates tumor necrosis factor-α induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in white and brown adipocytes.

Obesity involves hypoxic adipose tissue and low-grade chronic inflammation. We investigated the impact of hypoxia on inflammatory response to TNF-α in white and brown adipocytes. In response to TNF-α, the expression of the inducible enzymes iNOS and COX-2 was prominently and selectively potentiated during hypoxia while only moderately under normoxia. Levels of their products, nitrite and prostaglandinE2 were elevated accordingly. NS398, a selective COX-2 inhibitor, reduced nitrite levels. The expression of PGC-1α, a transcriptional co-activator involved in mitochondrial biogenesis, and PPARγ, a transcription factor involved in adipocyte homeostasis, was reduced by TNF-α during hypoxia. These results suggest that hypoxia potentiates the inflammatory response by TNF-α in both white and brown adipocytes and downregulates the transcription factors involved in adipocyte function.

Check-up examination: recommendations in adults.

Check-up examinations, or periodic health examinations (PHEs), have gained in importance during the last decades and are nowadays among the most common reasons for consultations in primary care settings. The aim of PHEs is to identify risk factors and early signs of disease, but also to prevent future illness by early intervention. Therefore, each PHE should include counselling, immunisation and physical examination according to the patient's age and gender. However, deciding whether to screen a patient and choosing the most appropriate screening method can be challenging for general practitioners. The U.S. Preventive Service Task Force (USPSTF) provides updated recommendations on different existing preventive care measures based on relevant literature review. The aim of this review is to provide an updated statement of recommendations regarding preventive care measures based mostly on the guidelines derived from the USPSTF and the Swiss Medical Board. Among the major updates, there is no recommendation anymore to routinely screen for breast cancer and prostate cancer in asymptomatic adults. Since 2013, however, the USPSTF recommends annual screening for lung cancer with low-dose CT in patients aged 55 to 80 years with a smoking history of ≥30 pack years. During PHEs, the physician should be alert to the patients' hidden agendas, which are the reason for one third of all consultations in primary care.

The lower quality of preventive care among forced migrants in a country with universal healthcare coverage.

OBJECTIVE: To assess the association between socio-demographic factors and the quality of preventive care and chronic care of cardiovascular (CV) risk factors in a country with universal health care coverage. METHODS: Our retrospective cohort assessed a random sample of 966 patients aged 50-80years followed over 2years (2005-2006) in 4 Swiss university primary care settings (Basel/Geneva/Lausanne/Zürich). We used RAND's Quality Assessment Tools indicators and examined recommended preventive care among different socio-demographic subgroups. RESULTS: Overall patients received 69.6% of recommended preventive care. Preventive care indicators were more likely to be met among men (72.8% vs. 65.4%; p<0.001), younger patients (from 71.0% at 50-59years to 66.7% at 70-80years, p for trend=0.03) and Swiss patients (71.1% vs. 62.7% in forced migrants; p=0.001). This latter difference remained in multivariate analysis adjusted for gender, age, civil status and occupation (OR 0.68; 95% CI 0.54-0.86). Forced migrants had lower scores for physical examination and breast and colon cancer screening (all p≤0.02). No major differences were seen for chronic care of CV risk factors. CONCLUSION: Despite universal healthcare coverage, forced migrants receive less preventive care than Swiss patients in university primary care settings. Greater attention should be paid to forced migrants for preventive care.

Rictor in perivascular adipose tissue controls vascular function by regulating inflammatory molecule expression.

OBJECTIVE: Perivascular adipose tissue (PVAT) wraps blood vessels and modulates vasoreactivity by secretion of vasoactive molecules. Mammalian target of rapamycin complex 2 (mTORC2) has been shown to control inflammation and is expressed in adipose tissue. In this study, we investigated whether adipose-specific deletion of rictor and thereby inactivation of mTORC2 in PVAT may modulate vascular function by increasing inflammation in PVAT. APPROACH AND RESULTS: Rictor, an essential mTORC2 component, was deleted specifically in mouse adipose tissue (rictor(ad-/-)). Phosphorylation of mTORC2 downstream target Akt at Serine 473 was reduced in PVAT from rictor(ad-/-) mice but unaffected in aortic tissue. Ex vivo functional analysis of thoracic aortae revealed increased contractions and impaired dilation in rings with PVAT from rictor(ad-/-) mice. Adipose rictor knockout increased gene expression and protein release of interleukin-6, macrophage inflammatory protein-1α, and tumor necrosis factor-α in PVAT as shown by quantitative real-time polymerase chain reaction and Bioplex analysis for the cytokines in the conditioned media, respectively. Moreover, gene and protein expression of inducible nitric oxide synthase was upregulated without affecting macrophage infiltration in PVAT from rictor(ad-/-) mice. Inhibition of inducible nitric oxide synthase normalized vascular reactivity in aortic rings from rictor(ad-/-) mice with no effect in rictor(fl/fl) mice. Interestingly, in perivascular and epididymal adipose depots, high-fat diet feeding induced downregulation of rictor gene expression. CONCLUSIONS: Here, we identify mTORC2 as a critical regulator of PVAT-directed protection of normal vascular tone. Modulation of mTORC2 activity in adipose tissue may be a potential therapeutic approach for inflammation-related vascular damage.

Loss of pim1 imposes a hyperadhesive phenotype on endothelial cells.

BACKGROUND: PIM1 is a constitutively active serine-threonine kinase regulating cell survival and proliferation. Increased PIM1 expression has been correlated with cancer metastasis by facilitating migration and anti-adhesion. Endothelial cells play a pivotal role in these processes by contributing a barrier to the blood stream. Here, we investigated whether PIM1 regulates mouse aortic endothelial cell (MAEC) monolayer integrity. METHODS: Pim1-/-MAEC were isolated from Pim1 knockout mice and used in trypsinization-, wound closure assays, electrical cell-substrate sensing, immunostaining, cDNA transfection and as RNA source for microarray analysis. RESULTS: Pim1-/-MAEC displayed decreased migration, slowed cell detachment and increased electrical resistance across the endothelial monolayer. Reintroduction of Pim1- cDNA into Pim1-/-MAEC significantly restored wildtype adhesive characteristics. Pim1-/--MAEC displayed enhanced focal adhesion and adherens junction structures containing vinculin and ß-catenin, respectively. Junctional molecules such as Cadherin 13 and matrix components such as Collagen 6a3 were highly upregulated in Pim1-/- cells. Intriguingly, extracellular matrix deposited by Pim1-/- cells alone was sufficient to induce the hyperadhesive phenotype in wildtype endothelial cells. CONCLUSION: Loss of Pim1 induces a strong adhesive phenotype by enhancing endothelial cell-cell and cell-matrix adhesion by the deposition of a specific extracellular matrix. Targeting PIM1 function therefore might be important to promote endothelial barrier integrity.

Nuclear PIM1 confers resistance to rapamycin-impaired endothelial proliferation.

The PIM serine/threonine kinases and the mTOR/AKT pathway integrate growth factor signaling and promote cell proliferation and survival. They both share phosphorylation targets and have overlapping functions, which can partially substitute for each other. In cancer cells PIM kinases have been reported to produce resistance to mTOR inhibition by rapamycin. Tumor growth depends highly on blood vessel infiltration into the malignant tissue and therefore on endothelial cell proliferation. We therefore investigated how the PIM1 kinase modulates growth inhibitory effects of rapamycin in mouse aortic endothelial cells (MAEC). We found that proliferation of MAEC lacking Pim1 was significantly more sensitive to rapamycin inhibition, compared to wildtype cells. Inhibition of mTOR and AKT in normal MAEC resulted in significantly elevated PIM1 protein levels in the cytosol and in the nucleus. We observed that truncation of the C-terminal part of Pim1 beyond Ser 276 resulted in almost exclusive nuclear localization of the protein. Re-expression of this Pim1 deletion mutant significantly increased the proliferation of Pim1(-/-) cells when compared to expression of the wildtype Pim1 cDNA. Finally, overexpression of the nuclear localization mutant and the wildtype Pim1 resulted in complete resistance to growth inhibition by rapamycin. Thus, mTOR inhibition-induced nuclear accumulation of PIM1 or expression of a nuclear C-terminal PIM1 truncation mutant is sufficient to increase endothelial cell proliferation, suggesting that nuclear localization of PIM1 is important for resistance of MAEC to rapamycin-mediated inhibition of proliferation.