The Doppler Perfusion Index of the Liver and the Underlying Duplex Sonography of Visceral Vessels-A Systematic and Comprehensive Evaluation of Reproducibility.

Prior to the curative resection of colorectal carcinoma (CRC) or pancreatic ductal adenocarcinoma (PDAC), the exclusion of hepatic metastasis using cross-sectional imaging is mandatory. The Doppler perfusion index (DPI) of the liver is a promising method for detecting occult liver metastases, but the underlying visceral duplex sonography is critically viewed in terms of its reproducibility. The aim of this study was to investigate systematically the reproducibility of the measured variables, the calculated blood flow, and the DPI. Between February and September 2023, two examinations were performed on 80 subjects within a period of 0-30 days and at two previously defined quality levels, aligned to the German standards of the DEGUM. Correlation analyses were carried out using Pearson's correlation coefficient (PCC) and the intraclass correlation coefficient (ICC). The diameters, blood flow, and DPI showed a high degree of agreement (PCC of 0.9 and ICC of 0.9 for AHP). Provided that a precise standard of procedure is adhered to, the Doppler examination of AHC, AHP, and PV yields very reproducible blood flows and DPI, which is a prerequisite for a comprehensive investigation of its prognostic value for the prediction of metachronous hepatic metastasis in the context of curatively treated CRC or PDAC.

Update on the risk assessment of a rehabilitation stay for patients after allogeneic stem cell transplantation.

OBJECTIVE: High-dose chemotherapy with allogeneic stem cell transplantation is the only chance of cure for many haemato-oncological patients. After such therapy, the immune system is weakened, and the contact with other people should therefore be limited as much as possible. The question arises whether a rehabilitation stay can be recommended to these patients, which risk factors for complications during the rehabilitation stay can be identified, and whether physicians and patients can be provided with decision-making aids as to when the optimal time is to start rehabilitation. METHODS: We report about 161 rehabilitation stays of patients after high-dose chemotherapy with allogeneic stem cell transplantation. Premature discontinuation of the rehabilitation was selected as the criterion for a serious complication during the rehabilitation and the underlying reasons were analysed. RESULTS: The rate of prematurely terminated rehabilitation stays (13.6%) corresponds to our previous result from 2020. The analysis of the reasons for early termination comes to the conclusion that the rehabilitation stay is only considered as a reason for termination in very few cases, if at all. The risk factors identified for premature termination of the rehabilitation stay were male sex, the period (days) between transplantation and the beginning of the rehabilitation stay, haemoglobin value, platelets and presence of immunosuppressing agent. The most significant risk factor is a decreased platelet count at the time rehabilitation begins. The platelet count, the likelihood that it will improve in the further course and the urgency of the rehabilitation stay can be used to help decide when the optimal time for rehabilitation is given. CONCLUSION: Rehabilitation can be recommended to patients after allogeneic stem cell transplantation. Based on various factors, recommendations can be made for the right time for rehabilitation.

Impact of SARS-CoV-2 pandemic on rehabilitation of patients after high-dose chemotherapy with allogeneic hematopoietic stem cell transplantation: results of a monocentric, retrospective analysis.

OBJECTIVE: Because immunocompromised patients are particularly vulnerable during the SARS-CoV-2 pandemic, patients undergoing high-dose chemotherapy with allogeneic hematopoietic stem cell transplantation (HDC/alloSCT) face the question of whether they should enter a rehabilitation stay. We therefore asked to what extent the pandemic has changed the acceptance of a rehabilitation stay and whether and how high the risk of infection for these patients should be assessed. METHODS: We analyzed all patients after HDC/alloSCT admitted to our rehabilitation facility during the period, since the first SARS-CoV-2 wave occurred in Germany (03/15/2020) and compared them with patients admitted to our rehabilitation facility before. RESULTS: Analysis of our data showed a significant reduction in rehabilitation stays of patients after HDC/alloSCT during the SARS-CoV-2 pandemic. Patients arrived for rehabilitation significantly later after HDC/alloSCT and were less likely to take immunosuppressive medications. The anxiety score in the HADS was lower and the platelet count was higher. In contrast, parameters such as age, sex, or leukocyte value did not play a role. None of the patients became infected with SARS-CoV-2 during rehabilitation. CONCLUSIONS: The acceptance of a rehabilitation stay during the SARS-CoV-2 pandemic has changed, but there does not seem to be an increased risk for the patients.

Rehabilitation of patients after CAR T-cell therapy. Experiences on 5 patients.

OBJECTIVE: CAR T-cell therapy is an effective treatment for various relapsed or refractory haemato-oncological diseases. However, this therapy results in significant immunosuppression that lasts for months. Whether these patients are at risk during a rehabilitation stay, e.g., due to infections, has not yet been answered. METHODS: We describe the rehabilitation stay under special hygienic conditions of the five patients rehabilitated in our clinic after CAR T-cell therapy. Complications that occurred during rehabilitation are reported, as well as the positive effects of rehabilitation on physical performance, polyneuropathic complaints, anxiety and depression, and individual limitations. RESULTS: One patient reported signs of infection already at the beginning of rehabilitation. This was treated with antibiotics, and rehabilitation could be continued. No complications occurred in any of the other patients. All patients reported having benefited physically and psychologically from the rehabilitation, and two expressed the intention to return to work. CONCLUSIONS: As far as we know, this is the first report on several patients after CAR T-cell therapy. Based on the limited data, there is no reason to withhold a rehabilitation stay from patients after CAR T-cell therapy.

Influence of Treatment Caused Impairments on Anxiety and Depression in Patients with Cancer of the Esophagus or the Esophagogastric Junction.

PURPOSE: After therapy of cancer of the esophagus or the esophagogastric junction, patients often suffer from anxiety and depression. Some risk factors for elevated anxiety and depression are reported, but the influence of steatorrhea, the frequency of which has only recently been reported, has not yet been investigated. METHOD: Using the Hospital Anxiety and Depression Scale (HADS), we analyzed the correlation of anxiety and depression with steatorrhea, appetite, and weight loss in 72 patients with cancer of the esophagus or of the esophagogastric junction, who were treated at our rehabilitation clinic between January 2011 and December 2014. In addition, effectiveness of psychological interviews was analyzed. RESULTS: We have evaluable anxiety questionnaires from 51 patients showing a median anxiety value of 5 (range 0-13). As for the depression, results from evaluable questionnaires of 54 patients also showed a median value of 5 (range 0-15). Increased anxiety and depression values (> 7) were observed in 25.4% and 37.0% of the patients respectively. Patients who were admitted with steatorrhea for rehabilitation showed a statistically higher anxiety value (median 6.3 vs. 4.7, p < 0.05), reduced appetite, and a weight loss above 15 kg depicting a correlation to anxiety and depression. Psychological conversations helped lowering the depression but had no influence on anxiety. CONCLUSIONS: Impairments after cancer treatment, such as steatorrhea, appetite loss, and weight loss, should be interpreted as an alarm signal and should necessitate screening for increased anxiety and depression. Psychological therapy can help improving the extent of the depression.

Does rehabilitation pose a risk to patients suffering from haemato-oncological diseases? Results of a monocentric, retrospective analysis in Germany.

OBJECTIVE: Patients suffering from haemato-oncological diseases tend to have a weakened immune system after the end of their therapy. To avoid infections, patients are advised to limit contact with other people. This poses the question whether a stay at a rehabilitation facility can be recommended. METHODS: We report about 134 rehabilitation stays of patients. Premature discontinuation of the rehabilitation stay was selected as the criterion for a serious complication during the rehabilitation, and the underlying reasons were analysed. RESULTS: Compared to the discontinuation rates of patients suffering from solid tumours (2.4%), the percentage of haemato-oncological patients ending prematurely their rehabilitation stay (8.2%) is significantly increased. This rises to 17.1% for patients who have undergone an allogeneic stem cell transplantation. The analysis of the discontinuation reasons revealed that they were not directly connected to the rehabilitation. Apart from the already known risk factors for premature termination of the rehabilitation stay, we have identified the period (days) between the last therapy and the beginning of the rehabilitation stay as a risk factor. CONCLUSIONS: We show for the first time that a rehabilitation stay does not pose additional risks for patients suffering from haemato-oncological diseases.

[Role of the microbiome in chronic wounds]. / Rolle des Mikrobioms bei chronischen Wunden.

BACKGROUND: The microbiome, collective microbial life in defined areas of the body, is of great importance. OBJECTIVE: What is the significance of the wound microbiome in the treatment of chronic wounds? Which interactions exist with other microbiomes and which conclusions can be drawn for wound management? MATERIALS AND METHODS: Swabs or debridement samples from wounds were analysed for microbial growth by culture or gene-based techniques. The genetic results are used to determine the wound microbiome. The pathogens were evaluated according to proportion of different species and related to different factors like type and location of wound, disease and underlying illnesses and to define the wound microbiome. RESULTS: In comparison with conventional microbiological detection methods the wound microbiome comprises many more types and quantities of species. The wound microbiome is related to skin microbiome showing complex and time-dependent composition, as well as inter- and intraindividual differences. Diabetic wounds exhibit disease-related changes, e.g. staphylococcal species dominate whereas streptococcal species dominate in nondiabetic wounds. CONCLUSIONS: The analysis of wound microbiome is still at an early stage; however it has already been shown that in hemodynamic disorders there are disease-specific relationships with the wound microbiome, which can also provide clues about the course of the disease. Phenomena from the skin microbiome should also be effective in wounds. In this context modern antimicrobial treatment options beyond conventional chemotherapy like colonization modulation become possible.

[Multiresistant Pathogens in Oncological and Cardiological Rehabilitation - Results of a Surveillance Study in Brandenburg]. / Multiresistente Erreger in der onkologischen und kardiologischen Rehabilitation ­ Ergebnisse einer Surveillancestudie in Brandenburg.

We investigated the prevalence of multidrug resistant pathogens in patients of oncologic and cardiologic rehabilitation units with 155 oncologic and 157 cardiologic patients undergoing microbiologic screening. It was found that 4.5% of oncologic as well as cardiologic patients were colonized with multidrug resistant pathogens. 2-MRGN and ESBL were the most encountered species (2.9%). 3-MRGN were found twice as frequent in oncologic patients (2.6 and 1.3%). Overall oncologic and cardiologic patients exhibit comparatively low prevalence rates for multidrug resistant pathogens.

Importance of Pancreatic Enzyme Replacement Therapy after Surgery of Cancer of the Esophagus or the Esophagogastric Junction.

After surgical treatment of cancer of the esophagus or the esophagogastric junction we observed steatorrhea, which is so far seldom reported. We analyzed all patients treated in our rehabilitation clinic between 2011 and 2014 and focused on the impact of surgery on digestion of fat. Reported steatorrhea was anamnestic, no pancreatic function test was made. Here we show the results from 51 patients. Twenty-three (45%) of the patients reported steatorrhea. Assuming decreased pancreatic function pancreatic enzyme replacement therapy (PERT) was started or modified during the rehabilitation stay (in the following called STEA+). These patients were compared with the patients without steatorrhea and without PERT (STEA-). Maximum weight loss between surgery and rehabilitation start was 18 kg in STEA+ patient and 15.3 kg in STEA- patients. STEA+ patients gained more weight under PERT during the rehabilitation phase (3 wk) than STEA- patients without PERT (+1.0 kg vs. -0.3 kg, P = 0.032). We report for the first time, that patients after cancer related esophageal surgery show anamnestic signs of exocrine pancreas insufficiency and need PERT to gain body weight.

Hyperspectral imaging as a novel diagnostic tool in microcirculation of wounds.

Monitoring of perfusion is a cornerstone in surgery, phlebology and basic science to proof wound healing by interventions. In chronic wound management it is of utmost importance to realize and parametrize wound bed perfusion to verify actual, and plan further treatment by noninvasive diagnostics. Up to now monitoring is based on visual inspection of wounds as conventionally practiced over more than decades. The main problems of visual inspection are the lack of standardization and comparability because of interindividual variations. Therefore technical performance with contact free probes based on standardized perfusion measuring is strongly needed. Hyperspectral imaging (HSI) was investigated to overcome manual and visual wound inspection in monitoring of wound healing. HSI works noninvasive, and imaging of relevant perfusion parameters is possible without the need of contrast enhancing drugs. METHODS: HSI technology uses imaging spectroscopic analysis in visual and near infrared spectrum to get information on imaged tissue in less than 10 s. Tissue is radiated by broad spectrum light and the following parameters are calculated from remitted spectra: the grade of oxygenation and the volume proportion of hemoglobin (in superficial and also deeper (8 mm) tissues. The calculated data comprise the "Tissue hemoglobin oxygen saturation" (StO2) as percental oxygenation index to assess superficial perfusion (VIS-spectrum), the "Near infrared perfusion" (NIR) to assess deeper perfusion (near infrared spectrum) and the "Tissue hemoglobin index" (THI) to measure the percental volume of hemoglobin of surface perfusion (VIS-spectrum). The measurements of these parameters are calculated as false color-coded perfusion results on screen.We investigated different kind of wounds (combustion, infection, ulcer wounds, wounds in immune disorders, trauma wounds) determining superficial and deeper oxygen saturation, hemoglobin distribution and water content using hyperspectral imaging with TIVITA™ Tissue system. RESULTS: Hyperspectral Imaging allowed easy real time determination and visualization of hemodynamically relevant parameters- superficial and deeper oxygen saturation, total hemoglobin and tissue water content. In the patient with scleroderma, acral lesions with decreased perfusion correlated well with necrotic skin aspects.HSI clearly revealed macroscopic conspicuous suture wounds after Dupuytren surgery, infected soft tissue wounds with strong inflammatory hyperemia, edema in burn injuries, spatial geometry of abscess formation and chronic ulcer wounds. All measurements influenced further surveillance decisions. Hyperspectral imaging seems suitable for routine diagnostics and monitoring of skin and soft tissue lesions like acute and chronic wounds. It allows surveillance of postoperative suture wounds and burn wounds. Special indications may be transplant surveillance and monitoring of therapeutical interventions.

Comparison between cold plasma, electrochemotherapy and combined therapy in a melanoma mouse model.

The study was undertaken to compare antitumor efficacy of electrochemotherapy (ECT) with cold plasma therapy (CP) in a melanoma mouse model. After melanoma implantation into the flank of C57BL/6N mice, CP by two different plasma sources (APPJ and DBD) was applied directly to the tumor surface. ECT was performed with bleomycin intravenously at a field strength of 1000 V/cm without or combined with CP. Primary endpoints were tumor growth acceleration (TGA), daily volume progression (DVP) and survival after treatment. Both plasma sources as single treatment showed a significant TGA delay, which proved less effective than ECT. CP (APPJ) combined with ECT (ECJ) significantly improved per cent mouse survival, with significant superiority compared with ECT. Plasma therapy alone albeit less effective seems a potential alternative to ECT in patients with melanoma and can be applied manifold in a session without general anaesthesia. Accordingly, CP alone and combined with ECT may serve as new option in palliative skin melanoma therapy.

TNFα-induced lysosomal membrane permeability is downstream of MOMP and triggered by caspase-mediated NDUFS1 cleavage and ROS formation.

When NF-κB activation or protein synthesis is inhibited, tumor necrosis factor alpha (TNFα) can induce apoptosis through Bax- and Bak-mediated mitochondrial outer membrane permeabilization (MOMP) leading to caspase-3 activation. Additionally, previous studies have implicated lysosomal membrane permeability (LMP) and formation of reactive oxygen species (ROS) as early steps of TNFα-induced apoptosis. However, how these two events connect to MOMP and caspase-3 activation has been largely debated. Here, we present the novel finding that LMP induced by the addition of TNFα plus cycloheximide (CHX), the release of lysosomal cathepsins and ROS formation do not occur upstream but downstream of MOMP and require the caspase-3-mediated cleavage of the p75 NDUFS1 subunit of respiratory complex I. Both a caspase non-cleavable p75 mutant and the mitochondrially localized antioxidant MitoQ prevent LMP mediated by TNFα plus CHX and partially interfere with apoptosis induction. Moreover, LMP is completely blocked in cells deficient in both Bax and Bak, Apaf-1, caspase-9 or both caspase-3 and -7. Thus, after MOMP, active caspase-3 exerts a feedback action on complex I to produce ROS. ROS then provoke LMP, cathepsin release and further caspase activation to amplify TNFα apoptosis signaling.

Plasma expansion into vacuum assuming a steplike electron energy distribution.

The expansion of a semi-infinite plasma slab into vacuum is analyzed with a hydrodynamic model implying a steplike electron energy distribution function. Analytic expressions for the maximum ion energy and the related ion distribution function are derived and compared with one-dimensional numerical simulations. The choice of the specific non-Maxwellian initial electron energy distribution automatically ensures the conservation of the total energy of the system. The estimated ion energies may differ by an order of magnitude from the values obtained with an adiabatic expansion model supposing a Maxwellian electron distribution. Furthermore, good agreement with data from experiments using laser pulses of ultrashort durations τ(L)

Circulating t(14;18)-positive cells in healthy individuals: association with age and sex but not with smoking.

Abstract t(14;18)-positive cells can be detected not only in patients with follicular lymphoma (FL) but also in healthy individuals (HIs). We used epidemiological data and blood samples of the population-based Study of Health in Pomerania (SHIP) to analyze associations of FL risk factors and t(14;18)-positive cells in HIs. Buffy coat samples from 4152 study participants were tested by real-time polymerase chain reaction (PCR) for t(14;18)-positive cells. Of 3966 evaluable subjects, 1526 were t(14;18)-PCR positive [38.5%, median 3.9 t(14;18)-positive per million nucleated cells, range 0.6-9299]. In multivariable analyses, age and sex but not parameters of smoking exposure were significantly associated with t(14;18) prevalence (logistic regression, p < 0.001). Multivariable analyses of t(14;18)-frequency showed a positive association with age but not with sex or smoking. These age and sex associations in HIs require careful control in future studies of t(14;18) as a potential biomarker of lymphoma risk.

Identification of a glutathione peroxidase inhibitor that reverses resistance to anticancer drugs in human B-cell lymphoma cell lines.

Cancer cells isolated from two patients with malignant non-Hodgkin B-cell lymphomas that became resistant to chemotherapy during clinical treatment were made ≥fourfold resistant in culture to anticancer drugs, that is cisplatin, etoposide, methotrexate and bortezomib. Because most resistant lines showed significantly increased expression of the anti-oxidative enzyme glutathione peroxidase 1 (GPx1), GPx1 was investigated as a target for inhibitor development. Virtual screening of a library of diverse structures by docking them to the active site of the X-ray crystal structure of bovine GPx1 uncovered compounds that might block the enzyme. An enzyme assay confirmed an acylhydrazone heterocycle (3) with GPx inhibitory activity. Combinations of 3 with the anticancer drugs listed above led to reversal of resistance in the lymphoma cell lines.

Statistical analysis of results obtained by real-time PCR for improvement of absolute quantification of target sequences.

BACKGROUND: Real-time quantitative PCR is increasingly used in clinical laboratories. Genomic DNA or plasmids containing cloned target sequences are necessary to generate data for standard curves. These data must be analysed to obtain the relative or absolute quantity of the target concentration in a sample. The method chosen for data analysis can strongly influence results of the quantification. Absolute quantification is important especially in clinical settings. For different reasons estimating the copy number of the gene of interest based on DNA concentration measurements is vague and tends toward overestimation, especially if cell lines are used. METHODS: Data gained by limiting dilution and multiple-tube approach were analyzed using our new Poisson distribution based software and were compared with results from DNA concentration measurement. Data from different cell sources (peripheral blood mononuclear cells and two cell lines) were compared: RESULTS: Limiting dilution and multiple-tube approach analyzed by a Poisson distribution simplifies and improves the generation of standard curves for real time PCR if cell lines are used. The absolute target copy number in a sample, the standard deviation, and a 95% confidence interval are calculated by the software. CONCLUSIONS: With this easy to use program a target copy number can be reliably quantified. The program is available free of charge from: http://www.medizin.uni-greifswald.de/InnereC/index.php?id=18 (link will be activated after acceptance of the paper).

Highly ordered palladium nanodot patterns for full concentration range hydrogen sensing.

A hydrogen sensor based on a novel fabrication process that combines the precision of advanced nano-fabrication techniques with a bottom-up process based on electrochemistry is presented. The sensor allows for reliable detection between 0.1% and 100% of H(2) in air. This fabrication is very versatile, highly reliable, and fully scalable for mass production, representing a very promising option for the fabrication of the next generation hydrogen sensors.

Toxoplasmosis after allogeneic stem cell transplantation--a single centre experience.

Toxoplasmosis is a rare but possibly underestimated complication following allogeneic stem cell transplantation with a high mortality rate. One reason might be the limitation of the diagnostic instruments relying mainly on imaging and molecular-based techniques. In this report, we present three cases of toxoplasmosis identified among 155 allograft recipients treated at Greifswald University Hospital. Widely disseminated toxoplasmosis was detected post-mortem in two patients allografted for high-risk multiple myeloma. Clinical signs suspicious for toxoplasmosis occurred after days +32 and +75, respectively. In one case, serology and conventional Toxoplasma gondii PCR, targeting the B1 gene, revealed negative results, while in the other patient, toxoplasmosis was not investigated. Both patients received pentamidine for Pneumocystis jirovecii pneumonia (PcP) prophylaxis. The third patient, a 68-year-old woman allografted for AML, developed cerebral toxoplasmosis from day +395 after allogeneic SCT with typical signs in magnetic resonance tomography. Toxoplasma DNA was amplified from one of two samples of cerebrospinal fluid. The patient died of disseminated toxoplasmosis despite immediate initiation of therapy. Retrospective comparative testing of clinical specimens by the conventional T. gondii PCR and by a real-time PCR targeting a 529-bp genomic fragment suggests a higher sensitivity of the latter method in our patients. In conclusion, we suggest a rigorous real-time PCR monitoring for high-risk patients or patients with signs of infections suspicious for toxoplasmosis, even though low-copy results are presently difficult to interpret. Our reported cases might also encourage the use of trimethoprim-sufmethoxazole instead of pentamidine for PcP prophylaxis in those patients.

5-alpha-reductase type I (SRD5A1) is up-regulated in non-small cell lung cancer but does not impact proliferation, cell cycle distribution or apoptosis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most frequent malignancies and has a high mortality rate due to late detection and lack of efficient treatments. Identifying novel drug targets for this indication may open the way for new treatment strategies. Comparison of gene expression profiles of NSCLC and normal adjacent tissue (NAT) allowed to determine that 5-alpha-reductase type I (SRD5A1) was up-regulated in NSCLC compared to NAT. This raised the question whether SRD5A1 was involved in sustained proliferation and survival of NSCLC. METHODS: siRNA-mediated silencing of SRD5A1 was performed in A549 and NCI-H460 lung cancer cell lines in order to determine the impact on proliferation, on distribution during the different phases of the cell cycle, and on apoptosis/necrosis. In addition, lung cancer cell lines were treated with 4-azasteroids, which specifically inhibit SRD5A1 activity, and the effects on proliferation were measured. Statistical analyses using ANOVA and post-hoc Tamhane-T2-test were performed. In the case of non-parametric data, the Kruskal-Wallis test and the post-hoc Mann-Whitney-U-test were used. RESULTS: The knock-down of SRDA51 expression was very efficient with the SRD5A1 transcripts being reduced to 10% of control levels. Knock-down efficiency was furthermore confirmed at the protein level. However, no effect of SRD5A1 silencing was observed in the proliferation assay, the cell cycle analysis, and the apoptosis/necrosis assay. Treatment of lung cancer cell lines with 4-azasteroids did not significantly inhibit proliferation. CONCLUSIONS: In summary, the results suggest that SRD5A1 is not a crucial enzyme for the sustained proliferation of NSCLC cell lines.