Bedside hyperspectral imaging indicates a microcirculatory sepsis pattern - an observational study.

INTRODUCTION: Microcirculatory alterations are key mechanisms in sepsis pathophysiology leading to tissue hypoxia, edema formation, and organ dysfunction. Hyperspectral imaging (HSI) is an emerging imaging technology that uses tissue-light interactions to evaluate biochemical tissue characteristics including tissue oxygenation, hemoglobin content and water content. Currently, clinical data for HSI technologies in critical ill patients are still limited. METHODS AND ANALYSIS: TIVITA® Tissue System was used to measure Tissue oxygenation (StO2), Tissue Hemoglobin Index (THI), Near Infrared Perfusion Index (NPI) and Tissue Water Index (TWI) in 25 healthy volunteers and 25 septic patients. HSI measurement sites were the palm, the fingertip, and a suprapatellar knee area. Septic patients were evaluated on admission to the ICU (E), 6 h afterwards (E+6) and three times a day (t3-t9) within a total observation period of 72 h. Primary outcome was the correlation of HSI results with daily SOFA-scores. RESULTS: Serial HSI at the three measurement sites in healthy volunteers showed a low mean variance expressing high retest reliability. HSI at E demonstrated significantly lower StO2 and NPI as well as higher TWI at the palm and fingertip in septic patients compared to healthy volunteers. StO2 and TWI showed corresponding results at the suprapatellar knee area. In septic patients, palm and fingertip THI identified survivors (E-t4) and revealed predictivity for 28-day mortality (E). Fingertip StO2 and THI correlated to SOFA-score on day 2. TWI was consistently increased in relation to the TWI range of healthy controls during the observation time. Palm TWI correlated positively with SOFA scores on day 3. DISCUSSION: HSI results in septic patients point to a distinctive microcirculatory pattern indicative of reduced skin oxygenation and perfusion quality combined with increased blood pooling and tissue water content. THI might possess risk-stratification properties and TWI could allow tissue edema evaluation in critically ill patients. CONCLUSION: HSI technologies could open new perspectives in microcirculatory monitoring by visualizing oxygenation and perfusion quality combined with tissue water content in critically ill patients - a prerequisite for future tissue perfusion guided therapy concepts in intensive care medicine.

[Microvascular changes in COVID-19]. / Mikrovaskuläre Veränderungen bei COVID-19.

BACKGROUND: Clinically, coronavirus disease 2019 (COVID-19) is associated with a wide range of symptoms, which can range from mild complaints of an upper respiratory infection to life-threatening hypoxic respiratory insufficiency and multiorgan failure. OBJECTIVE: The initially identified pulmonary damage patterns, such as diffuse alveolar damage in acute lung failure, are accompanied by new findings that draw a more complex scenario. These include microvascular involvement and a wide range of associated pathologies of multiple organ systems. A back-scaling of microstructural vascular changes is possible via targeted correlation of pathological autopsy results with radiological imaging. MATERIAL AND METHODS: Radiological and pathological correlation as well as microradiological imaging to investigate microvascular involvement in fatal COVID-19. RESULTS: The cases of two COVID-19 patients are presented. Patient 1 showed a relative hypoperfusion in lung regions that did not have typical COVID-19 infiltrates; the targeted post-mortem correlation also showed subtle signs of microvascular damage even in these lung sections. Patient 2 showed both radiologically and pathologically advanced typical COVID-19 destruction of lung structures and the case illustrates the damage patterns of the blood-air barrier. The perfusion deficit of the intestinal wall shown in computed tomography of patient 2 could not ultimately clearly be microscopically attributed to intestinal microvascular damage. CONCLUSION: In addition to microvascular thrombosis, our results indicate a functional pulmonary vasodysregulation as part of the pathophysiology during the vascular phase of COVID-19. The clinical relevance of autopsies and the integration of radiological imaging findings into histopathological injury patterns must be emphasized for a better understanding of COVID-19.

[Assessment of kidney function : Creatinine is not the whole story]. / Beurteilung der Nierenfunktion : Kreatinin ist nicht alles.

Chronic renal insufficiency has a high prevalence and leads not only to a severe impairment in the quality of life but also to a higher mortality, mainly due to cardiovascular complications; however, in the early stages where there is still a chance for a therapeutic intervention, it is often underestimated because depending on endogenous factors (e.g. age and muscle mass), serum creatinine could falsely remain in the normal range while kidney function is already impaired. An exact measurement of the glomerular filtration rate (GFR) using radionuclide techniques is cumbersome and usually confined to rare cases, such as in clinical studies. Creatinine clearance measurement by 24-h urine collection requires good patient instructions and is error prone, thus it is limited to special circumstances. In routine clinical practice, estimation of the GFR by calculation algorithms provides the best approach. In recent years the chronic kidney disease epidemiology collaboration (CKD-EPI) formula has become established as the most accurate method. This should be used for screening and continuous surveillance. In addition, urinalysis including dipstick tests and urinary microscopy represent non-invasive, technically simple and economic screening tools. Due to its semiquantitative nature, the results of urinalysis should only to be interpreted after comprehensive consideration of the diagnostic and technical limitations, which are reviewed in this article.

Humoral and Cellular Responses to a Single Dose of Fendrix in Renal Transplant Recipients with Non-response to Previous Hepatitis B Vaccination.

Approximately 70% of kidney transplant recipients are non-responders to conventional hepatitis B virus (HBV) vaccines. We examined whether Fendrix™, an HBV vaccine containing 3-O-desacyl-4'-monophosphoryl lipid A (MPL) as adjuvant, could induce HBV immunity in these patients and compared their vaccination efficacy with healthy controls tested previously by the same assays. We selected 35 kidney transplant recipients who had been vaccinated at least thrice against HBV but had never displayed anti-HBs antibodies. We re-assessed their anti-HBs antibody titres and further determined cellular HBV immunity by proliferation assay and interferon (IFN)-γ ELISpot. Seventeen recipients did neither display humoral nor cellular immunity and could be tested prior to and at month 1 after vaccination. Of note, HLA antigens associated with non-response to HBV vaccination (HLA-DRB1*03 and HLA-DQB1*02) were over-represented in these 17 recipients. At month 1 after a single vaccination with Fendrix™, we observed a significant increase in anti-HBs antibodies (P = 0.02). In seven of 17 recipients, we detected anti-HBs antibodies ≥10 IU/l (10-264), in four HBV-specific lymphocyte proliferation (stimulation index of 2.6-8.7) and in one specific IFN-γ responses (12 spots increment). The vaccination response to Fendrix™ was significantly higher (P = 0.035) than the response to HBVaxPro™ in young healthy controls. In summary, the results show that a single vaccination with Fendrix™ could already induce HBV-specific humoral and/or cellular responses in ten of 17 kidney transplant patients. Thus, Fendrix™ appears as an efficient vaccine in this patient cohort.

Toll-like receptor-mediated immune responses are attenuated in the presence of high levels of hepatitis B virus surface antigen.

It has been recently shown that Toll-like receptor (TLR) signalling in murine nonparenchymal liver cells (NPCs) is suppressed in the presence of Hepatitis B virus surface antigen (HBsAg). It is not clear, however, whether this is also relevant for the adaptive immune responses and how this effect is mediated. Peripheral blood mononuclear cells (PBMCs) from Hepatitis B virus (HBV) patients and controls were stimulated by TLR ligands in the absence or presence of autologous serum. Interestingly, TLR-mediated cytokine expression (Interleukin-6 and -10) as well as TLR3-induced interferon (IFN) expression in PBMCs of HBV patients was significantly higher than in the healthy volunteers, showing a negative correlation with the levels of HBsAg. In addition, TLR3-mediated IFN-γ production was inhibited in the presence of HBV-containing serum. To mechanistically analyse this observation, murine Kupffer cells (KCs) and sinusoidal endothelial cells (LSECs) were stimulated with TLR3 ligands in the presence or absence of HBsAg. Mixed lymphocyte reactions were performed to study T-cell activation induced by TLR-stimulated NPCs. Gene expression of cytokines and TLR3 was analysed by quantitative rt-PCR, and activation of transcription factors was assessed by Western blot or reporter gene assays. TLR-induced expression of interferon γ, interferon sensitive genes and proinflammatory cytokines in murine KCs and LSECs was efficiently suppressed in the presence of HBsAg, whereas the expression of anti-inflammatory cytokines was enhanced. Activation of NFκB, IRF-3 and MAPKs in these liver cells was potently suppressed by HBsAg. T-cell activation mediated through TLR3-stimulated KCs or LSECs was suppressed by HBsAg which could be reverted by anti-IL-10 antibodies. These findings may, at least in part, explain how HBV evades innate and adaptive immune responses to maintain a persistent infection.

Assessment of biophysical skin properties at different body sites in hospitalized old patients: results of a pilot study.

BACKGROUND: Skin aging is a risk factor for a decubitus and biophysical skin properties could help to identify persons at risk. Whether such biophysical properties of aged human skin differ between areas is undetermined. OBJECTIVE: To investigate whether viscoelasticity, hydration or friction differ between important areas for decubitus risk. METHODS: Pilot study in 32 (18 female, 14 male) acute and subacute old patients aged 81.9 ± 5.9 years (±SD), without active skin disease after an average of 10 days of stay. Assessment of skin resilience/viscoelasticity (E) and hydration (H) at the volar forearm (VF), trochanter (TR) and the sacrum (SA), nutrition by a Mini Nutritional Assessment (MNA), total body water (TBW), lean body mass (LBM), % body fat (%F) by bioimpedance and routine laboratory parameters (hemoglobin, hematocrit, leukocytes, C-reactive protein, serum proteins and creatinine). RESULTS: Mean body mass index (27 ± 4.2), MNA (22.5 ± 2.9), Braden score (20 ± 2.5), E (68.5 ± 6.0%) and H (38.3 ± 6.7) at any site and laboratory parameters did not differ by sex. Men had more TBW (+12 ± 1.5 liters), LBM (+9 ± 2 kg), less %F (-8.8 ± 2.1%), increased H-TR (+7.11 ± 2.8) and H-SA (+5.68 ± 2.5). Overall E-VF correlated significantly with E-TR (r(2) = 0.40, p < 0.0001) and E-SA (r(2) = 0.40, p < 0.0001). In contrast, skin hydration was not correlated. CONCLUSION: Results of forearm elasticity experiments can be used as a model for other body sites at risk for the development of pressure ulcers.

[Thrombotic occlusion of the extracorporeal circulation during hepatic chemosaturation despite targeted anticoagulation : A case report]. / Thrombotischer Verschluss der extrakorporalen Zirkulation während hepatischer Chemosaturation trotz zielgerechter Antikoagulation : Ein Fallbericht.

Percutaneous hepatic chemosaturation is a treatment option for unresectable primary or secondary liver tumors. In this procedure the part of the inferior vena cava (VCI) that collects blood from the hepatic veins is isolated using a double balloon catheter. Like this, systemic distribution of the chemotherapeutic agent melphalan which is administered via the hepatic artery can be prevented. After passage through the liver and drainage from the retrohepatic VCI, the chemosaturated blood passes through two extracorporeal filters. Subsequently, the filtered blood is returned via the jugular vein. The procedure is often accompanied by severe hemodynamic instability, the cause of which is still not completely understood. In addition, coagulation management of extracorporeal circulation is often challenging. The authors report a case in which a thrombus formed in the returning leg of the extracorporeal circulation despite sufficient activated clotting time (ACT). Targeted problem search and resolution were necessary simultaneously to hemodynamic stabilization and interdisciplinary collaboration to successfully perform the intervention and provide the patient with safe treatment.

[Safety and efficacy of en bloc vs. conventional transurethral resection of bladder tumors: a meta-analysis and systematic review]. / Sicherheit und Effizienz der en bloc vs. konventionellen transurethralen Resektion von Blasentumoren: eine Metaanalyse und systematic Review.

BACKGROUND: En bloc tumor resection of bladder tumors (ERBT) is a novel alternative procedure to conventional resection of bladder tumor (cTURBT), which might help to address common problems of the standard method, such as inadequate detrusor muscle in specimens, high re-resection rates and high recurrence rates. OBJECTIVE: To analyze current data on ERBT in efficacy and safety compared to cTURBT. DATA SOURCES: PubMed. STUDY SELECTION: Two independent authors identified trials based on keywords and inclusion criteria. A third author was consulted in case of discrepancies. Screening keywords: ERBT, en bloc transurethral resection of bladder tumor, TURBT en bloc. A meta-analysis of 13 studies was performed. The effect size was estimated based on odds ratios and mean differences including their corresponding two-sided 95% confidence intervals. DATA SYNTHESIS: The analyzed studies comprised a homogenous collective in terms of tumor size, tumor multiplicity and tumor stage. Operation time did not significantly differ between the methods. Differences were observed in hospitalization and catheterization time in favor of ERBT. Reported complications did not show clear differences. There was significantly more detrusor muscle in the specimens in the ERBT group. No significant differences were found in recurrence up to 2 years of follow-up. CONCLUSION: ERBT is a safe alternative to conventional TURBT with promising features regarding effective resection of detrusor muscle. More standardized data on recurrence rates, different resection modalities and resection margin results are needed.

Primary HHV 6 infection after liver transplantation with acute graft rejection and multi-organ failure: successful treatment with a 2.5-fold dose of cidofovir and reduction of immunosuppression.

HHV type 6 has been reported with enhanced pathogenicity in immunocompromised patients. Herein, we report about a two-yr-old girl who experienced primary HHV 6 infection after liver transplantation. She clinically presented with graft rejection and necrotic hepatitis as well as high fever, pneumonitis with respiratory failure and a rash. Therapy with cidofovir of 5 mg/kg per wk did not show improvement, so that a full pharmacokinetic profile of cidofovir was performed. It demonstrated enhanced body weight normalized clearance of cidofovir and cidofovir dosage was augmented to 12 mg/kg per wk to reach adequate drug exposure. With additional reduction of immunosuppression, the patient dramatically improved and liver function stabilized.