Search

The first set of data refers to PAR-2 gene expression with the target gene rbF2rl1 assessed in tenocytes harvested from New Zealand White Rabbits' Achilles tendons. These tenocytes were stimulated in vitro with 20 ng/mL platelet-derived growth factor-BB (PDGF-BB) and compared to the corresponding cell culture without growth factor PDGF-BB. In addition, three inhibitors were tested. In the presence or absence of 40 µM inhibitor concentration and 5 % fetal bovine serum, the following inhibitors were applied: SB203580 = inhibitor for MAPK; LY-294002 = inhibitor for PI3K; PD153035 = inhibitor for EGFR. As control, gene expression was assessed under DMSO = dimethyl sulfoxide (solvent of the inhibitors) or in medium = basal culture medium (with 10 % fetal bovine serum). The second set of data represents morphological aspects of cytoskeletal reorganization for rabbit Achilles tenocytes stimulated in vitro with 20 ng/mL PDGF-BB compared to the corresponding cell culture without PDGF-BB. Data on cell size, on F-actin immunohistochemical labeling intensity, α-tubulin immunohistochemical labeling intensity and on cell aspect ratio (length of the cell divided by its width) are presented. Moreover, analogous to the first set of data, cytoskeletal rearrangement in the presence or absence of the inhibitors SB203580, LY-294002 and PD153035 in the presence or absence of PDGF-BB were assessed., (© 2024 The Author(s).)

BACKGROUND Acute kidney injury (AKI) after orthotopic liver transplantation (OLT) contributes to morbidity and mortality. Donation after circulatory death (DCD) has been established to increase the pool of organs. While surgical complications are reported to be comparable in DCD and donation after brain death (DBD) OLT, there is a knowledge gap concerning adverse kidney events in these 2 groups. MATERIAL AND METHODS In this retrospective cohort study, 154 patients received a DBD and 68 received a DCD organ (2016-2020). The primary outcome was a major adverse kidney event within 30 days (MAKE-30). The secondary outcome was dynamics of AKI and kidney replacement therapy (KRT) during the first postoperative week and on postoperative day 30. Incidence and resolution from AKI and KRT and patient survival (PS) 30 days after OLT were compared between the DCD and DBD recipients. RESULTS MAKE-30 incidence after OLT was comparable in DCD (n=27, 40%) vs DBD (n=41, 27%) recipients (risk ratio 1.49 [95% CI 1.01, 2.21], p=0.073). AKI incidence was comparable in DCD (n=58, 94%) vs DBD (n=95, 82%) recipients (risk ratio 1.14 [95% CI: 1.03, 1.27], P=0.057). Overall, 40% (n=88) of patients required KRT, with no difference between DCD (n=27, 40%) vs DBD (n=61, 40%) recipients (risk ratio 1.00 [95% CI 0.71, 1.43], P>0.999). Resolution of AKI by day 30 was lower in DCD (n=29, 50%) than in DBD (n=66, 69%) recipients (risk ratio 0.71 [95% CI: 0.53, 0.95], P=0.032). Survival after 30 days (DCD: n=64, 94% vs DBD: n=146, 95%, risk ratio 0.99 [95% CI 0.93, 1.06], P>0.999) was also comparable. CONCLUSIONS MAKE-30, short-term renal outcome, and survival did not significantly differ between DBD and DCD-OLT. Resolution of AKI by day 30 was lower in DCD than in DBD recipients.

Background: Ischemia-reperfusion injury (IRI) is the pathophysiological hallmark of hepatic dysfunction after orthotopic liver transplantation (OLT). Related to IRI, early allograft dysfunction (EAD) after OLT affects short- and long-term outcome. During inflammatory states, the liver seems to be the main source of procalcitonin (PCT), which has been shown to increase independently of bacterial infection. This study investigates the association of PCT, IRI and EAD as well as the predictive value of PCT during the first postoperative week in terms of short- and long-term outcome after OLT., Methods: Patients ≥ 18 years undergoing OLT between January 2016 and April 2020 at the University Hospital of Zurich were eligible for this retrospective study. Patients with incomplete PCT data on postoperative days (POD) 1 + 2 or combined liver-kidney transplantation were excluded. The PCT course during the first postoperative week, its association with EAD, defined by the criteria of Olthoff, and IRI, defined as aminotransferase level > 2000 IU/L within 2 PODs, were analysed. Finally, 90-day as well as 12-month graft and patient survival were assessed., Results: Of 234 patients undergoing OLT, 110 patients were included. Overall, EAD and IRI patients had significantly higher median PCT values on POD 2 [31.3 (9.7-53.8) mcg/l vs. 11.1 (5.3-25.0) mcg/l; p < 0.001 and 27.7 (9.7-51.9) mcg/l vs. 11.5 (5.5-25.2) mcg/l; p < 0.001] and impaired 90-day graft survival (79.2% vs. 95.2%; p = 0.01 and 80.4% vs. 93.8%; p = 0.033). IRI patients with PCT < 15 mcg/l on POD 2 had reduced 90-day graft and patient survival (57.9% vs. 93.8%; p = 0.001 and 68.4% vs. 93.8%; p = 0.008) as well as impaired 12-month graft and patient survival (57.9% vs. 96.3%; p = 0.001 and 68.4% vs. 96.3%; p = 0.008), while the outcome of IRI patients with PCT > 15 mcg/l on POD 2 was comparable to that of patients without IRI/EAD., Conclusion: Generally, PCT is increased in the early postoperative phase after OLT. Patients with EAD and IRI have a significantly increased PCT maximum on POD 2, and impaired 90-day graft survival. PCT measurement may have potential as an additional outcome predictor in the early phase after OLT, as in our subanalysis of IRI patients, PCT values < 15 mcg/l were associated with impaired outcome., (© 2022. The Author(s).)

One great challenge in surgical tendon repair is the minimization of peritendinous adhesions. An electrospun tube can serve as a physical barrier around a conventionally sutured tendon. Six New Zealand White rabbits had one Achilles tendon fully transsected and sutured by a 4-strand suture. Another six rabbits had the same treatment, but with the additional electrospun DegraPol tube set around the sutured tendon. The adhesion formation to the surrounding tissue was investigated 12 weeks post-operation. Moreover, inflammation-related protease-activated receptor-2 (PAR-2) protein expression was assessed. Finally, rabbit Achilles tenocyte cultures were exposed to platelet-derived growth factor-BB (PDGF-BB), which mimicks the tendon healing environment, where PAR-2 gene expression was assessed as well as immunofluorescent staining intensity for F-actin and α-tubulin, respectively. At 12 weeks post-operation, the partially degraded DegraPol tube exhibited significantly lower adhesion formation (- 20%). PAR-2 protein expression was similar for time points 3 and 6 weeks, but increased at 12 weeks post-operation. In vitro cell culture experiments showed a significantly higher PAR-2 gene expression on day 3 after exposure to PDGF-BB, but not on day 7. The cytoskeleton of the tenocytes changed upon PDGF-BB stimulation, with signs of reorganization, and significantly decreased F-actin intensity. An electrospun DegraPol tube significantly reduces adhesion up to twelve weeks post-operation. At this time point, the tube is partially degraded, and a slight PAR-2 increase was detected in the DP treated tendons, which might however arise from particles of degrading DegraPol that were stained dark brown. PAR-2 gene expression in rabbit tenocytes reveals sensitivity at around day 10 after injury., (© 2021. The Author(s).)

Background: Severe coronavirus disease 2019 (COVID-19) frequently entails complications that bear similarities to autoimmune diseases. To date, there are little data on possible immunoglobulin (Ig) A-mediated autoimmune responses. Here, we aim to determine whether COVID-19 is associated with a vigorous total IgA response and whether IgA antibodies are associated with complications of severe illness. Since thrombotic events are frequent in severe COVID-19 and resemble hypercoagulation of antiphospholipid syndrome, our approach focused on antiphospholipid antibodies (aPL)., Methods: In this retrospective cohort study, clinical data and aPL from 64 patients with COVID-19 were compared from 3 independent tertiary hospitals (1 in Liechtenstein, 2 in Switzerland). Samples were collected from 9 April to 1 May 2020., Results: Clinical records of 64 patients with COVID-19 were reviewed and divided into a cohort with mild illness (mCOVID; 41%), a discovery cohort with severe illness (sdCOVID; 22%) and a confirmation cohort with severe illness (scCOVID; 38%). Total IgA, IgG, and aPL were measured with clinical diagnostic kits. Severe illness was significantly associated with increased total IgA (sdCOVID, P = .01; scCOVID, P < .001), but not total IgG. Among aPL, both cohorts with severe illness significantly correlated with elevated anticardiolipin IgA (sdCOVID and scCOVID, P < .001), anticardiolipin IgM (sdCOVID, P = .003; scCOVID, P< .001), and anti-beta 2 glycoprotein-1 IgA (sdCOVID and scCOVID, P< .001). Systemic lupus erythematosus was excluded from all patients as a potential confounder., Conclusions: Higher total IgA and IgA-aPL were consistently associated with severe illness. These novel data strongly suggest that a vigorous antiviral IgA response, possibly triggered in the bronchial mucosa, induces systemic autoimmunity., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Accurate risk stratification of critically ill patients with coronavirus disease 2019 (COVID-19) is essential for optimizing resource allocation, delivering targeted interventions, and maximizing patient survival probability. Machine learning (ML) techniques are attracting increased interest for the development of prediction models as they excel in the analysis of complex signals in data-rich environments such as critical care., Methods: We retrieved data on patients with COVID-19 admitted to an intensive care unit (ICU) between March and October 2020 from the RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry. We applied the Extreme Gradient Boosting (XGBoost) algorithm to the data to predict as a binary outcome the increase or decrease in patients' Sequential Organ Failure Assessment (SOFA) score on day 5 after ICU admission. The model was iteratively cross-validated in different subsets of the study cohort., Results: The final study population consisted of 675 patients. The XGBoost model correctly predicted a decrease in SOFA score in 320/385 (83%) critically ill COVID-19 patients, and an increase in the score in 210/290 (72%) patients. The area under the mean receiver operating characteristic curve for XGBoost was significantly higher than that for the logistic regression model (0.86  vs . 0.69, P  < 0.01 [paired t -test with 95% confidence interval])., Conclusions: The XGBoost model predicted the change in SOFA score in critically ill COVID-19 patients admitted to the ICU and can guide clinical decision support systems (CDSSs) aimed at optimizing available resources., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Chinese Medical Association. Published by Elsevier B.V.)

Aims of the Study: During the ongoing COVID-19 pandemic, the launch of a large-scale vaccination campaign and virus mutations have hinted at possible changes in transmissibility and the virulence affecting disease progression up to critical illness, and carry potential for future vaccination failure. To monitor disease development over time with respect to critically ill COVID-19 patients, we report near real-time prospective observational data from the RISC-19-ICU registry that indicate changed characteristics of critically ill patients admitted to Swiss intensive care units (ICUs) at the onset of a third pandemic wave., Methods: 1829 of 3344 critically ill COVID-19 patients enrolled in the international RISC-19-ICU registry as of 31 May 2021 were treated in Switzerland and were included in the present study. Of these, 1690 patients were admitted to the ICU before 1 February 2021 and were compared with 139 patients admitted during the emerging third pandemic wave RESULTS: Third wave patients were a mean of 5.2 years (95% confidence interval [CI] 3.2&ndash;7.1) younger (median 66.0 years, interquartile range [IQR] 57.0&ndash;73.0 vs 62.0 years, IQR 54.5&ndash;68.0; p &lt;0.0001) and had a higher body mass index than patients admitted in the previous pandemic period. They presented with lower SAPS II and APACHE II scores, less need for circulatory support and lower white blood cell counts at ICU admission. P/F ratio was similar, but a 14% increase in ventilatory ratio was observed over time (p = 0.03) CONCLUSION: Near real-time registry data show that the latest COVID-19 patients admitted to ICUs in Switzerland at the onset of the third wave were on average 5 years younger, had a higher body mass index, and presented with lower physiological risk scores but a trend towards more severe lung failure. These differences may primarily be related to the ongoing nationwide vaccination campaign, but the possibility that changes in virus-host interactions may be a co-factor in the age shift and change in disease characteristics is cause for concern, and should be taken into account in the public health and vaccination strategy during the ongoing pandemic. (ClinicalTrials.gov Identifier: NCT04357275).

Aims of the Study: Invasive streptococcal infections affect more than half a million patients worldwide every year and have a high lethality. Little is known about the epidemiology and microbiological characteristics of streptococcal infections in Switzerland. This case series study aims to describe the demographics, known risk factors for streptococcal skin and soft tissue infections, clinical presentations, treatment and outcomes of patients admitted to the University Hospital Zurich between 2000 and 2014 with invasive streptococcal infections caused by Streptococcus pyogenes (group A Streptococcus), Streptococcus dysgalactiae ssp. equisimilis or the Streptococcus anginosus group, as well as the microbiological characteristics of the clinical isolates., Methods: Data collected retrospectively from patients hospitalised between 2000 and 2014 with invasive streptococcal infections were analysed. M protein gene (emm) typing of the bacterial clinical isolates was carried out according to the Centers for Disease Control and Prevention guidelines., Results: A total of 86 patients with invasive beta-haemolytic streptococcal infections were included in this study, of which 49% presented with necrotising fasciitis (NF). The median age was 44 years and half were female. The most common risk factor was acute skin lesions. C-reactive protein levels were significantly higher in patients with NF, as were acute renal failure and distributive shock. Beta-lactam antibiotics were given to most patients, and intravenous immunoglobulins were given to 18% of patients within the first 24 hours. All patients suffering from NF underwent surgery. The overall case fatality rate was 8.1% at 30 days post admission. All Group A Streptococcus strains were susceptible to penicillin and clindamycin, and we found resistance to tetracycline in 11.9% of strains. The most common emm-type isolated was emm1 (44.4%)., Conclusions: Invasive beta-haemolytic streptococcal infections, the most severe presentation of which is NF, remain a serious clinical issue and require rapid diagnosis and treatment. This is the first representative analysis monitoring clinical and microbiological characteristics of patients with a severe invasive beta-haemolytic streptococcal infection and treated in Zurich, Switzerland. In addition to the detailed reporting of various clinical and microbiological characteristics, we show that C-reactive protein levels, acute renal failure and distributive shock were higher in the patients with NF. We also found a low case fatality rate compared to other reports. The detailed clinical data and microbiological characteristics depicted in this study will lead to a better understanding of regional differences in severe invasive streptococcal infections.

Objectives: Streptococcus pyogenes causes life-threatening invasive infections including necrotizing fasciitis (NF). Current treatment guidelines recommend the use of a cell-wall-active antibiotic combined with a protein synthesis inhibitor and surgical debridement in NF patients. Adjunctive therapy with intravenous immunoglobulin (IVIG) has been proposed for superantigen-associated streptococcal toxic shock syndrome. So far, benefits of IVIG treatment remain unclear and prospective clinical studies are scarce. Thus, we aimed to assess the effects of IVIG on virulence factor activity in vitro, ex vivo in patients and in vivo in a NF mouse model., Methods: We investigated the effect of IVIG on the activity of the virulence factors streptolysin O (SLO), streptodornase 1 (Sda1), S. pyogenes cell envelope protease and streptococcal pyrogenic exotoxin B in vitro and ex vivo in patient sera. Additionally, we assessed the influence of IVIG on the clinical outcome in a murine NF model., Results: In vitro, IVIG inhibited various streptococcal virulence factors. Further, IVIG treatment of group A Streptococcus-infected mice led to a reduced skin lesion size (median (interquartile range) day 3 intraperitoneal administration: 12 mm 2 (9-14.5) vs. 4 mm 2 (0.8-10.5), subcutaneous: 10.3 mm 2 (6.9-18.6) vs. 0.5 mm 2 (0.1-6.8)) and lower SLO activity. After treatment with IVIG, patient sera showed an elevated titre of specific SLO (7/9) and Sda1 (5/9) antibodies, reducing SLO and Sda1 activity., Conclusions: The clear reduction in disease severity in IVIG-treated mice and inhibition of virulence factor activity in mouse and human sera suggest that IVIG may be beneficial in invasive group A Streptococcus infections such as NF in addition to streptococcal toxic shock syndrome., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Transcranial color-coded Duplex sonography (TCCD) is a non-invasive bedside tool with broad diagnostic potential in the intensive care setting. Implementation of TCCD requires repeated reliable measurements of flow velocities despite data acquisition by multiple operators with varying experience. Thus the learning curve of TCCD and agreement of measurements between experienced and inexperienced operators is of great interest and unstudied so far., Methods: Six untrained ICU-residents and 2 trained operators participated and performed TCCD examinations of the mean cerebral artery (MCA) in 10 volunteers. Measurements of the residents were compared to the according measurements of the trained operators. Operators were either actively supervised during their first five examinations or performed the examinations without supervision., Results: A total of 480 measurements were obtained. Mean flow velocity (MFV) did not differ significantly between trained and untrained operators in the two groups (P=0.78 in not-supervised and P=0.82 in supervised group). We found a favorable learning curve in both groups (ICC 0.8, CI 95% 0.6-0.91- in not supervised and ICC 0.81 CI 95% 0.63-0.92 in supervised group). However, supervision helped trainees to acquire skills more rapidly and to perform more accurate measurements (ICC 0.77 (95% CI 0.39-0.94) to ICC 0.91 (95% CI 0.77-0.98) and ICC 0.66 (95% CI 0.11-0.91) to ICC 0.84 (95% CI 0.58-0.96), respectively., Conclusion: TCCD of the MCA in volunteers is an easy to learn tool with a favorable learning curve. A short-term learning program including initial supervised measurements yields reliable results in the hands of inexperienced operators.

A 52 year old Swiss presented with a sore throat and progressive hoarseness. The histology showed a granulomatous inflammation of the epiglottis. Microbiology revealed dimorphic fungi in the sputum which were identified as Histoplasma sp. The histoplasma antigen was positive in urine and serum. Antimycotic therapy with itraconazol p.o. was started and switched to Amphotericin B i. v. due to clinical deterioration. Adrenal insufficiency should be considered in any patient with disseminated histoplasmosis since both the infection as well as the antimycotic treatment may cause Morbus Addison. An alternative therapy for the disseminated histoplasmosis is voriconazol. The investigation of the travel history is an important point.