Artificial intelligence-based detection of pneumonia in chest radiographs

Artificial intelligence is gaining increasing relevance in the field of radiology. This study retrospectively evaluates how a commercially available deep learning algorithm can detect pneumonia in chest radiographs (CR) in emergency departments. The chest radiographs of 948 patients with dyspnea between 3 February and 8 May 2020, as well as 15 October and 15 December 2020, were used. A deep learning algorithm was used to identify opacifications associated with pneumonia, and the performance was evaluated by using ROC analysis, sensitivity, specificity, PPV and NPV. Two radiologists assessed all enrolled images for pulmonal infection patterns as the reference standard. If consolidations or opacifications were present, the radiologists classified the pulmonal findings regarding a possible COVID-19 infection because of the ongoing pandemic. The AUROC value of the deep learning algorithm reached 0.923 when detecting pneumonia in chest radiographs with a sensitivity of 95.4%, specificity of 66.0%, PPV of 80.2% and NPV of 90.8%. The detection of COVID-19 pneumonia in CR by radiologists was achieved with a sensitivity of 50.6% and a specificity of 73%. The deep learning algorithm proved to be an excellent tool for detecting pneumonia in chest radiographs. Thus, the assessment of suspicious chest radiographs can be purposefully supported, shortening the turnaround time for reporting relevant findings and aiding early triage

The voice of COVID-19: acoustic correlates of infection in sustained vowels

COVID-19 is a global health crisis that has been affecting many aspects of our daily lives throughout the past year. The symptomatology of COVID-19 is heterogeneous with a severity continuum. A considerable proportion of symptoms are related to pathological changes in the vocal system, leading to the assumption that COVID-19 may also affect voice production. For the very first time, the present study aims to investigate voice acoustic correlates of an infection with COVID-19 on the basis of a comprehensive acoustic parameter set. We compare 88 acoustic features extracted from recordings of the vowels /i:/, /e:/, /o:/, /u:/, and /a:/ produced by 11 symptomatic COVID-19 positive and 11 COVID-19 negative German-speaking participants. We employ the Mann-Whitney U test and calculate effect sizes to identify features with the most prominent group differences. The mean voiced segment length and the number of voiced segments per second yield the most important differences across all vowels indicating discontinuities in the pulmonic airstream during phonation in COVID-19 positive participants. Group differences in the front vowels /i:/ and /e:/ are additionally reflected in the variation of the fundamental frequency and the harmonics-to-noise ratio, group differences in back vowels /o:/ and /u:/ in statistics of the Mel-frequency cepstral coefficients and the spectral slope. Findings of this study can be considered an important proof-of-concept contribution for a potential future voice-based identification of individuals infected with COVID-19.Comment: 8 page

Strong Expression of Chemokine Receptor CXCR4 by Renal Cell Carcinoma Correlates with Advanced Disease

Diverse chemokines and their receptors have been associated with tumor growth, tumor dissemination, and local immune escape. In different tumor entities, the level of chemokine receptor CXCR4 expression has been linked with tumor progression and decreased survival. The aim of this study was to evaluate the influence of CXCR4 expression on the progression of human renal cell carcinoma. CXCR4 expression of renal cell carcinoma was assessed by immunohistochemistry in 113 patients. Intensity of CXCR4 expression was correlated with both tumor and patient characteristics. Human renal cell carcinoma revealed variable intensities of CXCR4 expression. Strong CXCR4 expression of renal cell carcinoma was significantly associated with advanced T-status (P = .039), tumor dedifferentiation (P = .0005), and low hemoglobin (P = .039). In summary, strong CXCR4 expression was significantly associated with advanced dedifferentiated renal cell carcinoma

Expression of chemokine receptor CXCR4 in esophageal squamous cell and adenocarcinoma

BACKGROUND: Prognosis of esophageal cancer is poor despite curative surgery. The chemokine receptor CXCR4 has been proposed to distinctly contribute to tumor growth, dissemination and local immune escape in a limited number of malignancies. The aim of our study was to evaluate the role of CXCR4 in tumor spread of esophageal cancer with a differentiated view of the two predominant histologic types – squamous cell and adenocarcinoma. METHODS: Esophageal cancer tissue samples were obtained from 102 consecutive patients undergoing esophageal resection for cancer with curative intent. The LSAB+ System was used to detect the protein CXCR4. Tumor samples were classified into two groups based on the homogeneous staining intensity. A cut-off between CXCR4w (= weak expression) and CXCR4s (= strong expression) was set at 1.5 (grouped 0 – 1.5 versus 2.0 – 3). Long-term survival rates were calculated using life tables and the Kaplan-Meier method. Using the Cox's proportional hazards analysis, a model of survival prediction was established. RESULTS: The overall expression rate for CXCR4 in esophageal squamous cell carcinoma was 94.1%. Subdividing these samples, CXCR4w was found in 54.9% and CXCR4s in 45.1%. In adenocarcinoma, an overall expression rate of 89.1% was detected with a weak intensitiy in 71.7% compared to strong staining in 29.3% (p = 0.066 squamous cell versus adenocarcinoma). The Cox's proportional hazards analysis identified the pM-category with a hazard ratio (HR) of 1.860 (95% CI: 1.014–3.414) (p = 0.045), the histologic tumor type (HR: 0.334; 95% CI: 0.180–0.618) (p = 0.0001) and the operative approach (transthoracic > transhiatal esophageal resection) (HR: 0.546; 95% CI: 0.324–0.920) (p = 0.023) as independent factors with a possible influence on the long-term prognosis in patients with esophageal carcinoma, whereas CXCR4 expression was statistically not significant (>0.05). CONCLUSION: Expression of the chemokine receptor CXCR4 in esophageal cancer is of major relevance in both histologic entities – squamous cell and adenocarcinoma. Though with lack of statistical significance, strong CXCR4 expression revealed a poorer long-term prognosis following curative esophagectomy in both histologic subtypes. Thus, the exact biological functions of CXCR4 in terms of tumor dissemination of esophageal cancer is yet undetermined. Inhibition of esophageal cancer progression by CXCR4 antagonists might be a promising therapeutic option in the future

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Effects of work conditions on provider mental well-being and quality of care: a mixed-methods intervention study in the emergency department

Abstract Background Emergency departments (EDs) are highly dynamic and stressful care environments that affect provider and patient outcomes. Yet, effective interventions are missing. This study evaluated prospective effects of a multi-professional organizational-level intervention on changes in ED providers’ work conditions and well-being (primary outcomes) and patient-perceived quality of ED care (secondary outcome). Methods A before and after study including an interrupted time-series (ITS) design over 1 year was established in the multidisciplinary ED of a tertiary referral hospital in Southern Germany. Our mixed-methods approach included standardized provider surveys, expert work observations, patient surveys, and register data. Stakeholder interviews were conducted for qualitative process evaluation. ITS data was available for 20 days pre- and post-intervention (Dec15/Jan16; Dec16/Jan17). The intervention comprised ten multi-professional meetings in which ED physicians and nurses developed solutions to work stressors in a systematic moderated process. Most solutions were consecutively implemented. Changes in study outcomes were assessed with paired t-tests and segmented regression analyses controlling for daily ED workload. Results One hundred forty-nine surveys were returned at baseline and follow-up (response at baseline: 76 out of 170; follow-up: 73 out of 157). Forty-one ED providers participated in both waves. One hundred sixty expert work observations comprising 240 observation hours were conducted with 156 subsequent work stress reports. One thousand four hundred eighteen ED patients were surveyed. Considering primary outcomes, respondents reported more job control and less overtime hours at follow-up. Social support, job satisfaction, and depersonalization deteriorated while respondents’ turnover intentions and inter-professional interruptions increased. Considering the secondary outcome, patient reports indicated improvements in ED organization and waiting times. Interviews revealed facilitators (e.g., comprehensive approach, employee participation) and barriers (e.g., understaffing, organizational constraints) for intervention implementation. Conclusions To the best of our knowledge, this is the first study to report prospective effects of an ED work system intervention on provider well-being and patient-perceived quality of ED care. We found inconsistent results with partial improvements in work conditions and patient perceptions of care. However, aspects of provider mental well-being deteriorated. Given the lack of organizational-level intervention research in EDs, our findings provide valuable insights into the feasibility and effects of participatory interventions in this highly dynamic hospital setting

Provider interruptions and patient perceptions of care: an observational study in the emergency department

BACKGROUND Interruptions are endemic in healthcare work environments. Yet, they can have positive effects in some instances and negative in others, with their net effect on quality of care still poorly understood. We aimed to distinguish beneficial and detrimental forms of interruptions of emergency department (ED) providers using patients' perceptions of ED care as a quality measure. METHODS An observational design was established. The study setting was an interdisciplinary ED of an academic tertiary referral hospital. Frequencies of interruption sources and contents were identified in systematic expert observations of ED physicians and nurses. Concurrently, patients rated overall quality of care, ED organisation, patient information and waiting times using a standardised survey. Associations were assessed with hierarchical linear models controlling for daily ED workload. Regression results were adjusted for multiple testing. Additionally, analyses were computed for ED physicians and nurses, separately. RESULTS On 40 days, 160 expert observation sessions were conducted. 1418 patients were surveyed. Frequent interruptions initiated by patients were associated with higher overall quality of care and ED organisation. Interruptions relating to coordination activities were associated with improved ratings of ED waiting times. However, interruptions containing information on previous cases were associated with inferior ratings of ED organisation. Specifically for nurses, overall interruptions were associated with superior patient reports of waiting time. CONCLUSIONS Provider interruptions were differentially associated with patient perceptions of care. Whereas coordination-related and patient-initiated interruptions were beneficial to patient-perceived efficiency of ED operations, interruptions due to case-irrelevant communication were related to inferior patient ratings of ED organisation. The design of resilient healthcare systems requires a thorough consideration of beneficial and harmful effects of interruptions on providers' workflows and patient safety

Multitasking behaviors and provider outcomes in emergency department physicians: two consecutive, observational and multi-source studies

Background!#!Multitasking is a key skill for emergency department (ED) providers. Yet, potentially beneficial or debilitating effects for provider functioning and cognition are underexplored. We therefore aimed to investigate the role of multitasking for ED physicians' work stress and situation awareness (SA).!##!Methods!#!Two consecutive, multi-source studies utilizing standardized expert observations in combination with physicians' self-reports on stress and SA were set out in an academic ED. To control for ED workload, measures of patient acuity, patient counts, and ED staff on duty were included. Regression analyses estimated associations between observed proportion of time spent in multitasking with matched ED physicians' reports on stress (study 1) and SA (study 2).!##!Results!#!ED physicians engaged between 18.7% (study 1) and 13.0% (study 2) of their worktime in multitasking. Self-reported as well as expert-observed multitasking were significantly associated. This confirms the internal validity of our observational approach. After controlling for ED workload, we found that physicians who engaged more frequently in multitasking perceived higher work stress (Beta = .02, 95%CI .001-.03; p = .01). In study 2, ED physicians with more frequent multitasking behaviors reported higher SA (B = .08, 95%CI .02-.14; p = .009).!##!Conclusions!#!Multitasking is often unavoidable in ED care. Our findings suggest that ED physicians' multitasking increases stress experiences, yet, may facilitate professional's experiences of situation awareness. Our results warrant further investigation into potentially ambivalent effects of ED providers' multitasking in effectively sharing time between competing demands while maintaining performance and safety