Multiple Abscess Collections: Antibiotics or Steroids?

Aseptic abscess syndrome (AAS) is a medical rarity. The combination of multiple abscess collections in different organs, negative microbiological studies, and the association with an inflammatory bowel disease is highly suggestive for an AAS. The AAS is an acute neutrophilic dermatosis, so "generalized pyoderma gangraenosum" or "generalized bullous sweet syndrome" might be used synonymously. It is important to note that the diagnosis of an AAS can be made only after careful exclusion of an infectious disease. Of interest, despite the severity of the inflammation, patients with AAS are commonly hemodynamically stable. To date, no studies have investigated the optimal regimen, dose, and duration of therapy. Corticosteroids are the cornerstone of immunosuppression during the acute phase. After the induction phase, therapy might be switched to anakinra or infliximab.

Diagnosis and treatment of right ventricular failure secondary to acutely increased right ventricular afterload (acute cor pulmonale): a clinical consensus statement of the Association for Acute CardioVascular Care of the European Society of Cardiology.

Acute right ventricular failure secondary to acutely increased right ventricular afterload (acute cor pulmonale) is a life-threatening condition that may arise in different clinical settings. Patients at risk of developing or with manifest acute cor pulmonale usually present with an acute pulmonary disease (e.g. pulmonary embolism, pneumonia, and acute respiratory distress syndrome) and are managed initially in emergency departments and later in intensive care units. According to the clinical setting, other specialties are involved (cardiology, pneumology, internal medicine). As such, coordinated delivery of care is particularly challenging but, as shown during the COVID-19 pandemic, has a major impact on prognosis. A common framework for the management of acute cor pulmonale with inclusion of the perspectives of all involved disciplines is urgently needed.

Recombinant C1 inhibitor in the prevention of severe COVID-19: a randomized, open-label, multi-center phase IIa trial.

Background: Conestat alfa (ConA), a recombinant human C1 inhibitor, may prevent thromboinflammation. Methods: We conducted a randomized, open-label, multi-national clinical trial in which hospitalized adults at risk for progression to severe COVID-19 were assigned in a 2:1 ratio to receive either 3 days of ConA plus standard of care (SOC) or SOC alone. Primary and secondary endpoints were day 7 disease severity on the WHO Ordinal Scale, time to clinical improvement within 14 days, and safety, respectively. Results: The trial was prematurely terminated because of futility after randomization of 84 patients, 56 in the ConA and 28 in the control arm. At baseline, higher WHO Ordinal Scale scores were more frequently observed in the ConA than in the control arm. On day 7, no relevant differences in the primary outcome were noted between the two arms (p = 0.11). The median time to defervescence was 3 days, and the median time to clinical improvement was 7 days in both arms (p = 0.22 and 0.56, respectively). Activation of plasma cascades and endothelial cells over time was similar in both groups. The incidence of adverse events (AEs) was higher in the intervention arm (any AE, 30% with ConA vs. 19% with SOC alone; serious AE, 27% vs. 15%; death, 11% vs. 0%). None of these were judged as being related to the study drug. Conclusion: The study results do not support the use of ConA to prevent COVID-19 progression. Clinical trial registration: https://clinicaltrials.gov, identifier NCT04414631.

[Vaskuläre Dyspnoe: Lungenembolie]. / Vaskuläre Dyspnoe: Lungenembolie.

INTRODUCTION: In clinical practice, the differentiation of pulmonary embolism from other entities often remains difficult. Of utmost importance is the estimation of the pretest probability of the disease: predictive scoring systems and the use of clinical gestalt are equally useful tools. Exclusion or confirmation of the disease requires the rationale use of additional investigations (laboratory, imaging). In this article, we provide clinical engrams and outline our diagnostic algorithm. Based on the latest recommendations, we summarize the therapeutic approach for patients with pulmonary embolism. The importance of follow-up visits after the initial event is discussed in the last part. The assessment of risk factors promoting the development of venous thromboembolism is crucial for estimating the risk of recurrence. Excessive screening (thrombophilia testing or tumor investigations) are of minor relevance.

Association of part-time clinical work with well-being and mental health in General Internal Medicine: A survey among Swiss hospitalists.

INTRODUCTION: Burnout and low job satisfaction are increasing among the General Internal Medicine (GIM) workforce. Whether part-time compared to full-time clinical employment is associated with better wellbeing, job satisfaction and health among hospitalists remains unclear. MATERIALS AND METHODS: We conducted an anonymized cross-sectional survey among board-certified general internists (i.e. hospitalists) from GIM departments in 14 Swiss hospitals. Part-time clinical work was defined as employment of <100% as a clinician. The primary outcome was well-being, as measured by the extended Physician Well-Being Index (ePWBI), an ePWBI ≥3 indicating poor wellbeing. Secondary outcomes included depressive symptoms, mental and physical health, and job satisfaction. We compared outcomes in part-time and full time workers using propensity score-adjusted multivariate regression models. RESULTS: Of 199 hospitalists invited, 137 (69%) responded to the survey, and 124 were eligible for analysis (57 full-time and 67 part-time clinicians). Full-time clinicians were more likely to have poor wellbeing compared to part-time clinicians (ePWBI ≥3 54% vs. 31%, p = 0.012). Part-time compared to full-time clinical work was associated with a lower risk of poor well-being in adjusted analyses (odds ratio 0.20, 95% confidence interval 0.07-0.59, p = 0.004). Compared to full-time clinicians, there were fewer depressive symptoms (3% vs. 18%, p = 0.006), and mental health was better (mean SF-8 Mental Component Summary score 47.2 vs. 43.2, p = 0.028) in part-time clinicians, without significant differences in physical health and job satisfaction. CONCLUSIONS: Full-time clinical hospitalists in GIM have a high risk of poor well-being. Part-time compared to full-time clinical work is associated with better well-being and mental health, and fewer depressive symptoms.

[Dyspnea and Right Heart Failure]. / Atemnot und Rechtsherzversagen.

Dyspnea and Right Heart Failure Abstract. Acute right ventricular failure is a critical condition diagnosed by clinical presentation combined with echocardiography. Additional diagnostic tools including laboratory, ECG, right heart catheterization, and other imaging modalities are needed to confirm the diagnosis and determine the cause. The identification and treatment of the underlying pathology, the reduction of right ventricular afterload (if possible), optimization of preload (often diuretics, rarely volume), and hemodynamic support using vasopressors and/or inodilators are mainstays of treatment. In severe cases, special therapies and mechanical circulatory support come into play.

Do we need blood culture stewardship programs? A quality control study and survey to assess the appropriateness of blood culture collection and the knowledge and attitudes among physicians in Swiss hospitals.

BACKGROUND: Guidance for blood culture (BC) collection is limited. Inappropriate BC collection may be associated with potentially harmful consequences for the patient such as unnecessary laboratory testing, treatment and additional costs. The aim of the study was to assess the appropriateness of BC collection and related knowledge and attitude of precribers. MATERIALS: We conducted a single-center quality control study to assess the appropriateness of BC collection according to the local guidelines in a Swiss university hospital in 2020 by combining three different approaches: point prevalence, patient-individual longitudinal and diseases-related analysis. Second, we conducted a survey regarding BC collection practices and knowledge among physicians in two non-university and one university hospital using an 18-item electronic questionnaire. RESULTS: We analyzed 1114 BC collected in 344 patients. Approximately 40% of the BCs were collected inappropriately, in particular in diseases with low pretest probability of bacteremia such as non-severe community acquired pneumonia (CAP). Follow-up blood culture (FUBC) collection was inappropriate in 60%. Growth of a relevant pathogen was more frequently observed in appropriately than in inappropriately collected BCs (18% vs. 3%, p < 0.001). In the survey, uncertainty concerning the need of index BC collection was high in non-severe CAP and uncomplicated cellulitis. CONCLUSIONS: Almost half of the BCs was not collected according to the guidelines, especially in non-severe CAP and in case of FUBCs. Substantial uncertainty among physicians regarding BC ordering practices was identified. The implementation of diagnostic stewardship programs may improve BC collection practices, increase adherence to local guidelines, and may help reducing unnecessary diagnostics and treatment.

Neutrophile-to-Lymphocyte Ratio (NLR) Identifies Patients with Coronavirus Infectious Disease 2019 (COVID-19) at High Risk for Deterioration and Mortality-A Retrospective, Monocentric Cohort Study.

Among people infected with SARS-CoV-2, the determination of clinical features associated with poor outcome is essential to identify those at high risk of deterioration. Here, we aimed to investigate clinical phenotypes of patients hospitalized due to COVID-19 and to examine the predictive value of the neutrophil-to-lymphocyte ratio (NLR) in a representative patient collective of the Swiss population. We conducted a retrospective monocentriccohort study with patients hospitalized due to COVID-19 between 27 February and 31 December 2020. Data were analyzed descriptively, using the binary logistic regression model, proportional odds logistic regression model, competing risk analysis, and summary measure analysis. A total of 454 patients were included in our study. Dyspnea, elevated respiratory rate, low oxygen saturation at baseline, age, and presence of multiple comorbidities were associated with a more severe course of the disease. A high NLR at baseline was significantly associated with disease severity, unfavorable outcome, and mortality. In non-survivors, NLR further increased during hospital stay, whereas in survivors, NLR decreased. In conclusion, our data emphasize the importance of accurate history taking and clinical examination upon admission and confirm the role of baseline NLR as a surrogate marker for increased disease severity, unfavorable outcome, and mortality in patients hospitalized due to infection with SARS-CoV-2.

External Validation of the Modified 4C Deterioration Model and 4C Mortality Score for COVID-19 Patients in a Swiss Tertiary Hospital.

Prognostic models to predict the deterioration and mortality risk in COVID-19 patients are utterly needed to assist in informed decision making. Most of these models, however, are at high risk of bias, model overfitting, and unclear reporting. Here, we aimed to externally validate the modified (urea was omitted) 4C Deterioration Model and 4C Mortality Score in a cohort of Swiss COVID-19 patients and, second, to evaluate whether the inclusion of the neutrophil-to-lymphocyte ratio (NLR) improves the predictive performance of the models. We conducted a retrospective single-centre study with adult patients hospitalized with COVID-19. Both prediction models were updated by including the NLR. Model performance was assessed via the models' discriminatory performance (area under the curve, AUC), calibration (intercept and slope), and their performance overall (Brier score). For the validation of the 4C Deterioration Model and Mortality Score, 546 and 527 patients were included, respectively. In total, 133 (24.4%) patients met the definition of in-hospital deterioration. Discrimination of the 4C Deterioration Model was AUC = 0.78 (95% CI 0.73-0.82). A total of 55 (10.44%) patients died in hospital. Discrimination of the 4C Mortality Score was AUC = 0.85 (95% CI 0.79-0.89). There was no evidence for an incremental value of the NLR. Our data confirm the role of the modified 4C Deterioration Model and Mortality Score as reliable prediction tools for the risk of deterioration and mortality. There was no evidence that the inclusion of NLR improved model performance.

T-cell recovery and evidence of persistent immune activation 12 months after severe COVID-19.

BACKGROUND: T-cell lymphopenia and functional impairment is a hallmark of severe acute coronavirus disease 2019 (COVID-19). How T-cell numbers and function evolve at later timepoints after clinical recovery remains poorly investigated. METHODS: We prospectively enrolled and longitudinally sampled 173 individuals with asymptomatic to critical COVID-19 and analyzed phenotypic and functional characteristics of T cells using flow cytometry, 40-parameter mass cytometry, targeted proteomics, and functional assays. RESULTS: The extensive T-cell lymphopenia observed particularly in patients with severe COVID-19 during acute infection had recovered 6 months after infection, which was accompanied by a normalization of functional T-cell responses to common viral antigens. We detected persisting CD4+ and CD8+ T-cell activation up to 12 months after infection, in patients with mild and severe COVID-19, as measured by increased HLA-DR and CD38 expression on these cells. Persistent T-cell activation after COVID-19 was independent of administration of a COVID-19 vaccine post-infection. Furthermore, we identified a subgroup of patients with severe COVID-19 that presented with persistently low CD8+ T-cell counts at follow-up and exhibited a distinct phenotype during acute infection consisting of a dysfunctional T-cell response and signs of excessive pro-inflammatory cytokine production. CONCLUSION: Our study suggests that T-cell numbers and function recover in most patients after COVID-19. However, we find evidence of persistent T-cell activation up to 12 months after infection and describe a subgroup of severe COVID-19 patients with persistently low CD8+ T-cell counts exhibiting a dysregulated immune response during acute infection.

Autoantibodies in COVID-19 correlate with antiviral humoral responses and distinct immune signatures.

BACKGROUND: Several autoimmune features occur during coronavirus disease 2019 (COVID-19), with possible implications for disease course, immunity, and autoimmune pathology. In this study, we longitudinally screened for clinically relevant systemic autoantibodies to assess their prevalence, temporal trajectory, and association with immunity, comorbidities, and severity of COVID-19. METHODS: We performed highly sensitive indirect immunofluorescence assays to detect antinuclear antibodies (ANA) and antineutrophil cytoplasmic antibodies (ANCA), along with serum proteomics and virome-wide serological profiling in a multicentric cohort of 175 COVID-19 patients followed up to 1 year after infection, eleven vaccinated individuals, and 41 unexposed controls. RESULTS: Compared with healthy controls, similar prevalence and patterns of ANA were present in patients during acute COVID-19 and recovery. However, the paired analysis revealed a subgroup of patients with transient presence of certain ANA patterns during acute COVID-19. Furthermore, patients with severe COVID-19 exhibited a high prevalence of ANCA during acute disease. These autoantibodies were quantitatively associated with higher SARS-CoV-2-specific antibody titers in COVID-19 patients and in vaccinated individuals, thus linking autoantibody production to increased antigen-specific humoral responses. Notably, the qualitative breadth of antibodies cross-reactive with other coronaviruses was comparable in ANA-positive and ANA-negative individuals during acute COVID-19. In autoantibody-positive patients, multiparametric characterization demonstrated an inflammatory signature during acute COVID-19 and alterations of the B-cell compartment after recovery. CONCLUSION: Highly sensitive indirect immunofluorescence assays revealed transient autoantibody production during acute SARS-CoV-2 infection, while the presence of autoantibodies in COVID-19 patients correlated with increased antiviral humoral immune responses and inflammatory immune signatures.

The AIFELL Score as a Predictor of Coronavirus Disease 2019 (COVID-19) Severity and Progression in Hospitalized Patients.

Since the beginning of the COVID-19 pandemic, SARS-CoV-2 has caused a global burden for health care systems due to high morbidity and mortality rates, leading to caseloads that episodically surpass hospital resources. Due to different disease manifestations, the triage of patients at high risk for a poor outcome continues to be a major challenge for clinicians. The AIFELL score was developed as a simple decision instrument for emergency rooms to distinguish COVID-19 patients in severe disease stages from less severe COVID-19 and non-COVID-19 cases. In the present study, we aimed to evaluate the AIFELL score as a prediction tool for clinical deterioration and disease severity in hospitalized COVID-19 patients. During the second wave of the COVID-19 pandemic in Switzerland, we analyzed consecutively hospitalized patients at the Triemli Hospital Zurich from the end of November 2020 until mid-February 2021. Statistical analyses were performed for group comparisons and to evaluate significance. AIFELL scores of patients developing severe COVID-19 stages IIb and III during hospitalization were significantly higher upon admission compared to those patients not surpassing stages I and IIa. Group comparisons indicated significantly different AIFELL scores between each stage. In conclusion, the AIFELL score at admission was useful to predict the disease severity and progression in hospitalized COVID-19 patients.

Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome.

Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which - combined with age, history of asthma bronchiale, and five symptoms during primary infection - is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS.

[A clear cerebrospinal fluid - but an unclear diagnosis]. / Liquor klar ­ Diagnose (un)klar.

HISTORY: A 35-year-old, previously healthy woman presented with short history of headache and fever. Several other family members reported active hand, foot, and mouth disease. FINDINGS: Clinical findings showed subfebrile temperatures and a prominent meningism. Cerebrospinal fluid and computed tomography of the head were unrevealing. Subsequent PCR-analysis of the cerebrospinal fluid was positive for Enteroviral-RNA. DIAGNOSIS AND THERAPY: Enteroviral-meningitis was diagnosed. The empirically administered antimicrobial therapy was stopped and further diagnostic tests could be withheld. COURSE: Symptom-oriented therapy resulted in complete resolution within the next few days. CONCLUSIONS: Our case emphasizes that, in patients with typical signs of meningeal irritation, normal cellular analysis of the cerebrospinal fluid does not exclude the presence of infectious meningitis. The astute clinician should be reminded that this constellation is highly suggestive of enteroviral meningitis.

Profound dysregulation of T cell homeostasis and function in patients with severe COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and shows a broad clinical presentation ranging from asymptomatic infection to fatal disease. A very prominent feature associated with severe COVID-19 is T cell lymphopenia. However, homeostatic and functional properties of T cells are ill-defined in COVID-19. METHODS: We prospectively enrolled individuals with mild and severe COVID-19 into our multicenter cohort and performed a cross-sectional analysis of phenotypic and functional characteristics of T cells using 40-parameter mass cytometry, flow cytometry, targeted proteomics, and functional assays. RESULTS: Compared with mild disease, we observed strong perturbations of peripheral T cell homeostasis and function in severe COVID-19. Individuals with severe COVID-19 showed T cell lymphopenia and redistribution of T cell populations, including loss of naïve T cells, skewing toward CD4+ T follicular helper cells and cytotoxic CD4+ T cells, and expansion of activated and exhausted T cells. Extensive T cell apoptosis was particularly evident with severe disease and T cell lymphopenia, which in turn was accompanied by impaired T cell responses to several common viral antigens. Patients with severe disease showed elevated interleukin-7 and increased T cell proliferation. Furthermore, patients sampled at late time points after symptom onset had higher T cell counts and improved antiviral T cell responses. CONCLUSION: Our study suggests that severe COVID-19 is characterized by extensive T cell dysfunction and T cell apoptosis, which is associated with signs of homeostatic T cell proliferation and T cell recovery.