Tocilizumab in Severe COVID-19 Pneumonia and Concomitant Cytokine Release Syndrome

Younger patients with COVID-19 may experience an exaggerated immune response to SARS-CoV-2 infection and develop cytokine release syndrome (CRS), which may be life threatening. There is no proven antiviral therapy for COVID-19 so far, but profound immunosuppression has recently been suggested as a treatment for COVID-19-associated CRS. We present a case of life-threatening CRS caused by COVID-19 infection with a favourable response to immunosuppressive therapy with tocilizumab (TCZ). The rapid clinical and biochemical improvement following TCZ administration suggests that treatment with immunotherapy can be life-saving in selected patients with COVID-19-induced CRS

Chronic Q fever diagnosis—consensus guideline versus expert opinion

Chronic Q fever, caused by Coxiella burnetii, has high mortality and morbidity rates if left untreated. Controversy about the diagnosis of this complex disease has emerged recently. We applied the guideline from the Dutch Q Fe­ver Consensus Group and a set of diagnostic criteria pro­posed by Didier Raoult to all 284 chronic Q fever patients included in the Dutch National Chronic Q Fever Database during 2006–2012. Of the patients who had proven cas­es of chronic Q fever by the Dutch guideline, 46 (30.5%) would not have received a diagnosis by the alternative cri­teria designed by Raoult, and 14 (4.9%) would have been considered to have possible chronic Q fever. Six patients with proven chronic Q fever died of related causes. Until results from future studies are available, by which current guidelines can be modified, we believe that the Dutch lit­erature-based consensus guideline is more sensitive and easier to use in clinical practice

Study protocol for a multicentre prospective cohort study to identify predictors of adverse outcome in older medical emergency department patients (the Risk Stratification in the Emergency Department in Acutely Ill Older Patients (RISE UP) study)

Abstract Background Older patients (≥65 years old) experience high rates of adverse outcomes after an emergency department (ED) visit. Reliable tools to predict adverse outcomes in this population are lacking. This manuscript comprises a study protocol for the Risk Stratification in the Emergency Department in Acutely Ill Older Patients (RISE UP) study that aims to identify predictors of adverse outcome (including triage- and risk stratification scores) and intends to design a feasible prediction model for older patients that can be used in the ED. Methods The RISE UP study is a prospective observational multicentre cohort study in older (≥65 years of age) ED patients treated by internists or gastroenterologists in Zuyderland Medical Centre and Maastricht University Medical Centre+ in the Netherlands. After obtaining informed consent, patients characteristics, vital signs, functional status and routine laboratory tests will be retrieved. In addition, disease perception questionnaires will be filled out by patients or their caregivers and clinical impression questionnaires by nurses and physicians. Moreover, both arterial and venous blood samples will be taken in order to determine additional biomarkers. The discriminatory value of triage- and risk stratification scores, clinical impression scores and laboratory tests will be evaluated. Univariable logistic regression will be used to identify predictors of adverse outcomes. With these data we intend to develop a clinical prediction model for 30-day mortality using multivariable logistic regression. This model will be validated in an external cohort. Our primary endpoint is 30-day all-cause mortality. The secondary (composite) endpoint consist of 30-day mortality, length of hospital stay, admission to intensive- or medium care units, readmission and loss of independent living. Patients will be followed up for at least 30 days and, if possible, for one year. Discussion In this study, we will retrieve a broad range of data concerning adverse outcomes in older patients visiting the ED with medical problems. We intend to develop a clinical tool for identification of older patients at risk of adverse outcomes that is feasible for use in the ED, in order to improve clinical decision making and medical care. Trial registration Retrospectively registered on clinicaltrials.gov (NCT02946398; 9/20/2016)

A new simplified model for predicting 30-day mortality in older medical emergency department patients:The rise up score

Background/Objectives: Currently, accurate clinical models that predict short-term mortality in older (&gt;= 65 years) emergency department (ED) patients are lacking. We aimed to develop and validate a prediction model for 30-day mortality in older ED patients that is easy to apply using variables that are readily available and reliably retrievable during the short phase of an ED stay.Methods: Prospective multi-centre cohort study in older medical ED patients. The model was derived through logistic regression analyses, externally validated and compared with other well-known prediction models (Identification of Seniors at Risk (ISAR), ISAR-Hospitalised Patients, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Modified Early Warning Score (MEWS)).Results: Within 30 days after presentation, 66 (10.9%) of 603 patients in the derivation cohort and 105 (13.3%) of 792 patients in the validation cohort died. The newly developed model included 6 predictors: age, &gt;= 2 abnormal vital signs, serum albumin, blood urea nitrogen, lactate dehydrogenase, and bilirubin. The discriminatory value of the model for mortality was very good with an AUC of 0.84 in the derivation and 0.83 in the validation cohort. The final model was excellently calibrated (Hosmer-Lemeshow p-value 0.89). The discriminatory value of the model was significantly higher than that of the four risk stratification scores (highest AUC of 0.69 for ISAR score, p-value 0.007).Conclusion: We developed and externally validated an accurate and simplified prediction model for 30-day mortality in older ED patients. This model may be useful to identify patients at risk of short-term mortality and to apply personalised medical care.</p

Short-term mortality in older medical emergency patients can be predicted using clinical intuition:A prospective study

<div><p>Background</p><p>Older emergency department (ED) patients are at risk for adverse outcomes, however, it is hard to predict these. We aimed to assess the discriminatory value of clinical intuition, operationalized as disease perception, self-rated health and first clinical impression, including the 30-day surprise question (SQ: “Would I be surprised if this patient died in the next 30 days” of patients, nurses and physicians. Endpoints used to evaluate the discriminatory value of clinical intuition were short-term (30-day) mortality and other adverse outcomes (intensive/medium care admission, prolonged length of hospital stay, loss of independent living or 30-day readmission).</p><p>Methods</p><p>In this prospective, multicentre cohort study, older medical patients (≥65 years), nurses and physicians filled in scores regarding severity of illness and their concerns (i.e. disease perception and clinical impression scores) immediately after arrival of the patient in the ED. In addition, patients filled in a self-rated health score and nurses and physicians answered the SQ. Area under the curves (AUCs) of receiver operating characteristics (ROCs) were calculated.</p><p>Results</p><p>The median age of the 602 included patients was 79 years and 86.7% were community dwelling. Within 30 days, 66 (11.0%) patients died and 263 (43.7%) patients met the composite endpoint. The severity of concern score of both nurses and physicians yielded the highest AUCs for 30-day mortality (for both 0.75; 95%CI 0.68–0.81). AUCs for the severity of illness score and SQ of nurses and physicians ranged from 0.71 to 0.74 while those for the disease perception and self-rated health of patients ranged from 0.64 to 0.69. The discriminatory value of the scores for the composite endpoint was lower (AUCs ranging from 0.60 to 0.67). We used scores that have not been previously validated which could influence their generalisability.</p><p>Conclusion</p><p>Clinical intuition,—disease perception, self-rated health and first clinical impression—documented at an early stage after arrival in the ED, is a useful clinical tool to predict mortality and other adverse outcomes in older ED patients. Highest discriminatory values were found for the nurses’ and physicians’ severity of concern score. Intuition may be helpful for the implementation of personalised medical care in the future.</p></div

Sex differences in clinical presentation and mortality in emergency department patients with sepsis

BACKGROUND: There is growing awareness that sex differences are associated with different patient outcomes in a variety of diseases. Studies investigating the effect of patient sex on sepsis-related mortality remain inconclusive and mainly focus on patients with severe sepsis and septic shock in the intensive care unit. We therefore investigated the association between patient sex and both clinical presentation and 30-day mortality in patients with the whole spectrum of sepsis severity presenting to the emergency department (ED) who were admitted to the hospital. MATERIALS AND METHODS: In our multi-centre cohort study, we retrospectively investigated adult medical patients with sepsis in the ED. Multivariable analysis was used to evaluate the association between patient sex and all-cause 30-day mortality. RESULTS: Of 2065 patients included, 47.6% were female. Female patients had significantly less comorbidities, lower Sequential Organ Failure Assessment score and abbreviated Mortality Emergency Department Sepsis score, and presented less frequently with thrombocytopenia and fever, compared to males. For both sexes, respiratory tract infections were predominant while female patients more often had urinary tract infections. Females showed lower 30-day mortality (10.1% vs. 13.6%;  = .016), and in-hospital mortality (8.0% vs. 11.1%;  = .02) compared to males. However, a multivariable logistic regression model showed that patient sex was not an independent predictor of 30-day mortality (OR 0.90; 95% CI 0.67-1.22;  = .51). CONCLUSIONS: Females with sepsis presenting to the ED had fewer comorbidities, lower disease severity, less often thrombocytopenia and fever and were more likely to have a urinary tract infection. Females had a lower in-hospital and 30-day mortality compared to males, but sex was not an independent predictor of 30-day mortality. The lower mortality in female patients may be explained by differences in comorbidity and clinical presentation compared to male patients.KEY MESSAGESOnly limited data exist on sex differences in sepsis patients presenting to the emergency department with the whole spectrum of sepsis severity.Female sepsis patients had a lower incidence of comorbidities, less disease severity and a different source of infection, which explains the lower 30-day mortality we found in female patients compared to male patients.We found that sex was not an independent predictor of 30-day mortality; however, the study was probably underpowered to evaluate this outcome definitively

SIEVE ELEMENT-LINING CHAPERONE1 restricts aphid feeding on arabidopsis during heat stress

The role of phloem proteins in plant resistance to aphids is still largely elusive. By genome-wide association mapping of aphid behavior on 350 natural Arabidopsis thaliana accessions, we identified the small heat shock-like SIEVE ELEMENT-LINING CHAPERONE1 (SLI1). Detailed behavioral studies on near-isogenic and knockout lines showed that SLI1 impairs phloem feeding. Depending on the haplotype, aphids displayed a different duration of salivation in the phloem. On sli1 mutants, aphids prolonged their feeding sessions and ingested phloem at a higher rate than on wild-type plants. The largest phenotypic effects were observed at 26°C, when SLI1 expression is upregulated. At this moderately high temperature, sli1 mutants suffered from retarded elongation of the inflorescence and impaired silique development. Fluorescent reporter fusions showed that SLI1 is confined to the margins of sieve elements where it lines the parietal layer and colocalizes in spherical bodies around mitochondria. This localization pattern is reminiscent of the clamp-like structures observed in previous ultrastructural studies of the phloem and shows that the parietal phloem layer plays an important role in plant resistance to aphids and heat stress