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Purpose Spinal injections are increasingly used for back pain treatment. Vertebral osteomyelitis (VO) after spinal injection (SIVO) is rare, but patient characteristics and outcome have not been well characterized. The aim of this study was to assess patient characteristics of SIVO in comparison to patients with native vertebral osteomyelitis (NVO) and to determine predictors for 1-year survival. Methods This is a single-center cohort study from a tertiary referral hospital. This is a retrospective analysis of Patients with VO who were prospectively enrolled into a spine registry from 2008 to 2019. Student’s t-test, Kruskal–Wallis test or Chi-square test were applied for group comparisons. Survival analysis was performed using a log-rank test and a multivariable Cox regression model. Results 283 VO patients were enrolled in the study, of whom 44 (15.5%) had SIVO and 239 (84.5%) NVO. Patients with SIVO were significantly younger, had a lower Charlson comorbidity index and a shorter hospital stay compared to NVO. They also showed a higher rate of psoas abscesses and spinal empyema (38.6% [SIVO] vs. 20.9% [NVO]). Staphylococcus aureus (27%) and coagulase-negative staphylococci (CNS) (25%) were equally often detected in SIVO while S. aureus was more frequently than CNS in NVO (38.1% vs. 7.9%).Patients with SIVO (P = 0.04) had a higher 1-year survival rate (Fig. 1). After multivariate analysis, ASA score was associated with a lower 1-year survival in VO. Conclusion The results from this study emphasize unique clinical features of SIVO, which warrant that SIVO should be estimated as a separate entity of VO.

Was ist neu? Periprothetische Infektionen: Diagnostik, Prothesenerhalt und Therapielänge. Nach einer neuen Studie kann bei Vorliegen einer hämatogenen periprothetischen Infektion und weiteren einliegenden Gelenkprothesen, die in der klinischen Untersuchung unauffällig sind, auf weitere invasive oder bildgebende Diagnostik verzichtet werden. Periprothetische Infektionen, die spät auftreten (> 3 Monate nach Implantation) haben ein schlechteres Outcome. Neue Studien versuchen Faktoren zu identifizieren, wann der Prothesenerhalt weiterhin eine Option ist. Eine neue randomisierte Landmarkstudie aus Frankreich konnte keine Nichtunterlegenheit für 6 versus 12 Wochen Therapielänge zeigen. Somit ist anzunehmen, dass dies aktuell der Standard für alle OP-Modalitäten (Erhalt oder Wechsel) wird. Wünschenswert wären weitere Studien zu dem Thema, die v.a. mehr Patienten mit spätem Prothesenwechsel betrachten. Spondylodiszitis: Inzidenz und Erregerprofil. Die Spondylodiszitis ist eine eher seltene Knocheninfektion, deren Inzidenz in den vergangenen Jahren aber weiter stark gestiegen ist (erneut fast verdoppelt in 10 Jahren). Betroffen sind weiterhin vor allem ältere Personen, Männer und komorbide Patienten. Eine retrospektive Studie aus Korea von Kim et al. gibt Aufschluss über die Erregerverteilung in verschiedenen Altersgruppen sowie mit verschiedenen Komorbiditäten. Damit hilft sie bei der Einschätzung des verursachenden Erregers und der Auswahl der empirischen Therapie, wenn die Erregeridentifizierung vor Therapiestart nicht gelingt. S. aureus ist am häufigsten über alle Altersgruppen, aber mit Zunahme von Enterokokken und v.a. gram-negativen Erregern bei Älteren. Diabetische Fußinfektion: Leitlinien, Diagnostik und Therapielänge. Die Leitlinien der „International Working Group on the Diabetic Foot“ (IWGDF) wurden mit leicht veränderter Klassifikation aktualisiert, außerdem hat die Deutsche Diabetes Gesellschaft neue Handlungsempfehlungen publiziert. Die empirische Therapie richtet sich weiterhin nach der Schwere der Infektion und weiteren Risikofaktoren (wie Vortherapien, Ischämie). Die mikrobiologische Diagnostik aus Gewebeproben wird gegenüber Abstrichen als überlegen beschrieben. Nach einer randomisierten Pilotstudie scheinen 3 Wochen Therapiedauer bei Osteomyelitis nach Debridement 6 Wochen nicht unterlegen zu sein. Größere randomisierte Studien zu dem Thema rekrutieren aktuell.

Purpose The incidence of bone and joint infections is increasing while their treatment remains a challenge. Although guidelines and recommendations exist, evidence is often lacking and treatment complicated by complex clinical presentations and therapeutic options. Interdisciplinary boards shown to improve management of other diseases, seem potentially helpful. We describe the establishment of an osteomyelitis board to show the existing demand for such a platform. Methods All patients discussed in the board for bone and joint infections between October 2014 and September 2020 were included in this retrospective study. Data were extracted from patient records and analyzed descriptively. Results A total of 851 requests related to 563 patients were discussed in the board during the study period. After a run-in period of 3 years, a stable number of cases (> 170/year) were discussed, submitted by nearly all hospital departments (22 of 25). Recommendations were mainly related to antibiotic treatment (43%) and to diagnostics (24%). Periprosthetic joint infections were the most frequent entity (33%), followed by native vertebral osteomyelitis and other osteomyelitis. In 3% of requests, suspected infection could be excluded, in 7% further diagnostics were recommended to confirm or rule out infection. Conclusions A multidisciplinary board for bone and joint infections was successfully established, potentially serving as a template for further boards. Recommendations were mainly related to antibiotic treatment and further diagnostics, highlighting the need for interdisciplinary discussion to individualize and optimize treatment plans based on guidelines. Further research in needed to evaluate impact on morbidity, mortality and costs.

Staphylococcus aureus (SA) and Streptococcus species (SS) show different clinical manifestations in infective endocarditis (IE), but the impact on the complexity of surgical treatment remains unclear. All patients with surgically treated IE due to SA or SS between July 2013 and December 2016 were extracted from a prospectively collected, single-center registry. Data on patient characteristics, surgical procedures, and postprocedural outcomes were collected. SA-IE was more common with prosthetic valves (26.3% vs. 7.3%, p = 0.04), cardiac devices (14.3% vs. 0%, p = 0.03), previous cardiac surgery (28.6% vs. 9.8%, p = 0.03), intravenous drug abuse (14.3% vs. 0%, p = 0.03), and embolic events (57.1% vs. 26.8%, p = 0.007). Preoperative CRP was significantly higher in SA-IE (median 96.1 mg/L vs. 42.4 mg/L, p = 0.002). Otherwise, SS-IE affected more cusps/leaflets (mean 2.4 vs. 1.8, p = 0.03) and led to more valve dysfunction (83.8% vs. 54.3%, p = 0.007). Surgery times did not differ between the groups, though patients with SA spent more time in the intensive care unit (median 7 vs. 4.5 days, p = 0.04). Hospital mortality did not differ, but patients with SA-IE had unfavorable long-term survival (p = 0.001). Future studies need to be larger and focus on the mechanism behind the reduced long-term survival to mitigate the deleterious effect of SA in surgically treated patients with IE.

Isolation of confirmed or suspected coronavirus disease 2019 (COVID-19) cases is essential but, as symptoms of COVID-19 are non-specific and test results not immediately available, case identification at admission remains challenging. To inform optimization of triage algorithms, patient flow and patient care, we analyzed characteristics of patients admitted to an isolation ward, both severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2) positive patients and patients in which initial suspicion was not confirmed after appropriate testing.Data from patients with confirmed or suspected COVID-19 treated in an isolation unit were analyzed retrospectively. Symptoms, comorbidities and clinical findings were analyzed descriptively and associations between patient characteristics and final SARS-CoV-2 status were assessed using univariate regression.Eighty three patients (49 SARS-CoV-2 negative and 34 positive) were included in the final analysis. Of initially suspected COVID-19 cases, 59% proved to be SARS-CoV-2-negative. These patients had more comorbidities (Charlson Comorbidity Index median 5(interquartile range [IQR] 2.5, 7) vs 2.7(IQR 1, 4)), and higher proportion of active malignancy than patients with confirmed COVID-19 (47% vs 15%; P = .004), while immunosuppression was frequent in both patient groups (20% vs 21%; P = .984). Of SARS-CoV-2 negative patients, 31% were diagnosed with non-infectious diseases.A high proportion of patients (59%) triaged to the isolation unit were tested negative for SARS-CoV-2. Of these, many suffered from active malignancy (47%) and were immunosuppressed (20%). Non-infectious diseases were diagnosed in 31%, highlighting the need for appropriate patient flow, timely expert medical care including evaluation for differential diagnostics while providing isolation and ruling out of COVID-19 in these patients with complex underlying diseases.

Summary Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding Sanofi and Regeneron Pharmaceuticals.

COVID-19 is a life threatening disease, caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with undergoing treatment for hematologic malignancies including hematopoietic stem cell transplantation are considered to be at particular risk for fatal outcomes [1, 2]. This report describes for the first time the detection of SARS-CoV-2 viremia prior to the onset of symptoms and diagnosis of COVID-19 in a 51-year-old patient with acute myeloid leukemia (AML) and relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Notably, we illustrate that SARS-CoV-2 viremia inversely correlates with anti-SARS-CoV-2 antibody production, which predates negativity in respiratory samples for 4 weeks. A 51-year-old female patient was admitted to the University Hospital of Cologne on March 9, 2020, with herpes zoster involving C8/Th1 and Enterococcus faecalis bloodstream infection in the context of a third relapse of a FLT-3 mutated AML after an allo-HSCT from her HLA-identical brother in 2017. At this point, she presented with CTC (Common Toxicity Criteria) grade IV neutropenia and thrombocytopenia. Antibiotic and antiviral treatment was initiated. The patient received Midostaurin and Gemtuzumab ozogamicin as treatment for the relapsed AML. Under this therapy, the general condition of the patient improved, with symptoms and inflammatory parameters retreating. However, on March 21, 2020, 11 days after admission, the patient developed fever with temperatures up to 38.4 °C combined with a dry cough and fatigue. SARS-CoV-2 infection was confirmed in a PCR analysis of a pharyngeal swab on March 23, 2020. Laboratory results showed an increase in inflammatory parameters such as ferritin, C-reactive protein (CRP) and interleukin (IL)-6 (Fig. 1). A computed tomography (CT) scan showed infiltrates characteristic of COVID-19 pneumonia (see Supplementary Fig. 1). The patient rapidly developed dyspnea, peripheral blood oxygen saturation decreased and non-invasive oxygen supplementation was required (Fig. 1). Following, IL-6 and ferritin levels increased fast correlating with clinical decline. Under the assumption of a hyperinflammatory syndrome, the patient received Tocilizumab twice in a 7 days interval due to not satisfactory recovery after the first dose. After anti-IL6 treatment, symptoms decreased as well as inflammatory parameters (Fig. 1). The patient recovered slowly in the following 6 weeks: fever subsided with the exception of a new catheter-associated soft-tissue infection after 6 weeks. Oxygen supplementation could be slowly reduced and a progressive decrease of inflammatory parameters was observed. The patient was finally discharged seven weeks after admission and referred to our outpatient clinic for further treatment of her AML. a Real-time PCR Cycle threshold (RT-PCR Ct) values for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in blood samples and IgG antibody ratios. The dotted horizontal line marks the detection line of RNA, as well as the threshold for antibody seroconversion. Onset of symptoms defined as day 0, presented with grey vertical dotted line. Onset and end of viremia presented with red vertical dotted lines. Negative RT-PCR test results are displayed as Ct (Cycle threshold) values of 42. b RT-PCR Ct values for SARS-CoV-2 RNA in respiratory samples and corresponding IgG antibody ratios. c Maximum Temperature measured on each day in °C and maximum oxygen supply in l/min on each day over the course of disease. Fever is defined as a temperature >38.0 °C. d Levels of CRP (C-reactive protein) in mg/l, ferritin in μg/l and interleukin (IL)-6 in ng/l over the course of disease. Respiratory and plasma specimens were collected routinely for SARS-CoV-2 real-time PCR (RT-PCR) and antibody testing (detailed information is reported in Supplementary Materials). The publication of this data was approved by the Institutional Review Board of the University of Cologne (20-1254) and the patient’s written informed consent obtained. SARS-CoV-2 viremia was first detected on March 19, 2020, 2 days before the first symptoms (fever and dry cough) occurred and inflammatory parameters began to rise. Thus, we confirmed the presence of SARS-CoV-2 viremia 4 days before the detection of SARS-CoV-2 RNA in pharyngeal swab (Fig. 1). Analyzing the virus-related molecular and serological parameters throughout the course of disease, the progressive increase of detected SARS-CoV-2 RNA in the evaluated plasma samples reached a peak 8 days after the first detection in blood, whereas the last positive evidence of SARS-CoV-2 RNA in plasma was observed on April 14, 2020. On the same date, corresponding to 24 days after initial symptoms, SARS-CoV-2 specific IgA and IgG antibodies were detected (above threshold of 1.1). Along the course, the increase of specific SARS-CoV-2 antibody levels correlated with viral clearance from the blood (Fig. 1). However, SARS-CoV-2 RT-PCR from respiratory samples remained positive for three more weeks (7 weeks in total), despite occurrence of seroconversion, disappearance of COVID-19 related symptoms, and normalized inflammatory markers. Finally, 51 days after the onset of symptoms, the patient was tested SARS-CoV-2 negative in respiratory specimen (Fig. 1). The present report describes a case of SARS-CoV-2 viremia, preceding COVID-19 symptoms for 2 days, indicating a clear link between the observed SARS-CoV-2 viremia and beginning of COVID-19 symptoms. Consecutively, this suggests that SARS-CoV-2 viremia might play a more crucial role in COVID-19 than previously assumed because viremia before onset of symptoms is possible at least in a portion of cases. So far, SARS-CoV-2 RNA detected in blood has been considered a bystander effect, assuming that it is an avital virus component [3]. However, the detection of viremia prior to the onset of clinical symptoms suggests a systemic infection with...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a global health emergency. To improve the understanding of the systemic component of SARS-CoV-2, we investigated if viral load dynamics in plasma and respiratory samples are associated with antibody response and severity of coronavirus disease 2019 (COVID-19). SARS-CoV-2 RNA was found in plasma samples from 14 (44%) out of 32 patients. RNAemia was detected in 5 out of 6 fatal cases. Peak IgG values were significantly lower in mild/moderate than in severe (0.6 (interquartile range, IQR, 0.4–3.2) vs. 11.8 (IQR, 9.9–13.0), adjusted p = 0.003) or critical cases (11.29 (IQR, 8.3–12.0), adjusted p = 0.042). IgG titers were significantly associated with virus Ct (Cycle threshold) value in plasma and respiratory specimens ((ß = 0.4, 95% CI (confidence interval, 0.2; 0.5), p < 0.001 and ß = 0.5, 95% CI (0.2; 0.6), p = 0.002). A classification as severe or a critical case was additionally inversely associated with Ct values in plasma in comparison to mild/moderate cases (ß = −3.3, 95% CI (−5.8; 0.8), p = 0.024 and ß = −4.4, 95% CI (−7.2; 1.6), p = 0.007, respectively). Based on the present data, our hypothesis is that the early stage of SARS-CoV-2 infection is characterized by a primary RNAemia, as a potential manifestation of a systemic infection. Additionally, the viral load in plasma seems to be associated with a worse disease outcome.

Nanoparticle‐based targeted drug delivery holds promise for treatment of cancers. However, most approaches fail to be translated into clinical success due to ineffective tumor targeting in vivo. Here, the delivery potential of mesoporous silica nanoparticles (MSN) functionalized with targeting ligands for epidermal growth factor receptor and C─C chemokine receptor type 2 is explored in lung tumors. The addition of active targeting ligands on MSNs enhances their uptake in vitro but fails to promote specific delivery to tumors in vivo, when administered systemically via the blood or locally to the lung into immunocompetent murine lung cancer models. Ineffective tumor targeting is due to efficient clearance of the MSNs by the phagocytic cells of the liver, spleen, and lung. These limitations, however, are successfully overcome using a novel organ‐restricted vascular delivery (ORVD) approach. ORVD in isolated and perfused mouse lungs of Kras‐mutant mice enables effective nanoparticle extravasation from the tumor vasculature into the core of solid lung tumors. In this study, ORVD promotes tumor cell‐specific uptake of nanoparticles at cellular resolution independent of their functionalization with targeting ligands. Organ‐restricted vascular delivery thus opens new avenues for optimized nanoparticles for lung cancer therapy and may have broad applications for other vascularized tumor types.