Teleconsultation at Sea and Acute Wound Management Onboard.

Introduction: The French Tele-Medical Assistance Service (TMAS) provides medical teleconsultation for any ship at sea. At the end of the consultation, the doctor decides whether the problem can be taken care of onboard or not. In this study, we determined the factors associated with the decision for disembarkation or evacuation in case of wounds. Methods: We conducted a retrospective epidemiological study between 2011 and 2019 from consultations with the French TMAS. The inclusion criterion was the presence of an acute wound. Results: One thousand six patients (n = 1,006) were analyzed and 586 (58%) patients were disembarked or evacuated. Factors associated with disembarkation or evacuation are wound characteristics (severity and location), the onboard staff's medical training, the availability of photography, and the ship's location. Wound severity is a risk factor for disembarkation or evacuation. The availability of photography, staff with advanced training, and being at >1 day of navigation from a harbor are protective factors against being disembarked or evacuated. Conclusion: The added value of photography and an update of medium medical training could increase the number of wounds taken care of onboard.

Theoretical analysis of effects of transcranial magneto-acoustical stimulation on neuronal spike-frequency adaptation.

BACKGROUND: Transcranial magneto-acoustical stimulation (TMAS) is a noninvasive technique that has advantages in spatial resolution and penetration depth. It changes the firing properties of neurons through the current generated by focused ultrasound and a static magnetic field. Spike-frequency adaptation is an important dynamic characteristic of neural information processing. METHODS: To address the effects of TMAS on neural spike-frequency adaptation, this study employs some ultrasound and magnetic field parameters, such as magnetic flux density, ultrasonic intensity, fundamental ultrasonic frequency, modulation frequency, and duty cycle. Using these different ultrasound and magnetic field parameters, membrane potential curves, spike-frequency curves, and adapted onset spike-frequency curves are exhibited and analyzed. RESULTS: The results show that spike-frequency adaptation is strongly dependent on ultrasonic intensity and magnetic flux density and is rarely affected by other parameters. However, modulation frequency and duty cycle influence membrane potentials and spike frequencies to some degree. CONCLUSIONS: This study reveals the mechanism of the effects of TMAS on neural spike-frequency adaptation and serves as theoretical guidance for TMAS experiments.

The utility of platelet activation biomarkers in thrombotic microangiopathies.

Primary thrombotic microangiopathies (TMAs) are observed in thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), while secondary TMAs have a wide range of etiologies. Early diagnosis and treatment of TMA are critical for patient well-being; however, distinguishing TTP from HUS on presentation is particularly challenging. Thrombocytopenia and platelet activation are central to different types of TMAs, thus limiting the utility of standard diagnostic approaches to evaluate the platelet function and hemostatic capacity. Alternative means of quantifying and monitoring changes to platelet activation and function are urgently needed. Activated platelets have been shown to interact with proteins of the complement and coagulation cascades and form part of inflammation processes engaged in TMA. Increased levels of platelet surface receptors as well as increased plasma levels of platelet-derived soluble proteins have been reported in TMAs. Elevated levels of platelet-leukocyte aggregates and platelet microparticles are also reported in different types of TMAs. Larger prospective evaluations of platelet activation markers in TMA using standardized assays, with comparison to cohorts of patients with thrombosis, coagulopathy, and thrombocytopenia, to evaluate the clinical usefulness of platelet markers in TMA are now needed. This review will summarize the current knowledge around platelet activation markers and critically evaluate their utility in diagnosis and prognosis of TMA patients.

Ultrasound Ultrafast Power Doppler Imaging with High Signal-to-Noise Ratio by Temporal Multiply-and-Sum (TMAS) Autocorrelation.

Coherent plane wave compounding (CPWC) reconstructs transmit focusing by coherently summing several low-resolution plane-wave (PW) images from different transmit angles to improve its image resolution and quality. The high frame rate of CPWC imaging enables a much larger number of Doppler ensembles such that the Doppler estimation of blood flow becomes more reliable. Due to the unfocused PW transmission, however, one major limitation of the Doppler estimation in CPWC imaging is the relatively low signal-to-noise ratio (SNR). Conventionally, the Doppler power is estimated by a zero-lag autocorrelation which reduces the noise variance, but not the noise level. A higher-lag autocorrelation method such as the first-lag (R(1)) power Doppler image has been developed to take advantage of the signal coherence in the temporal direction for suppressing uncorrelated random noises. In this paper, we propose a novel Temporal Multiply-and-Sum (TMAS) power Doppler detection method to further improve the noise suppression of the higher-lag method by modulating the signal coherence among the temporal correlation pairs in the higher-lag autocorrelation with a tunable pt value. Unlike the adaptive beamforming methods which demand for either receive-channel-domain or transmit-domain processing to exploit the spatial coherence of the blood flow signal, the proposed TMAS power Doppler can share the routine beamforming architecture with CPWC imaging. The simulated results show that when it is compared to the original R(1) counterpart, the TMAS power Doppler image with the pt value of 2.5 significantly improves the SNR by 8 dB for the cross-view flow velocity within the Nyquist rate. The TMAS power Doppler, however, suffers from the signal decorrelation of the blood flow, and thus, it relies on not only the pt value and the flow velocity, but also the flow direction relative to the geometry of acoustic beam. The experimental results in the flow phantom and in vivo dataset also agree with the simulations.

Current advances and challenges in CAR T-Cell therapy for solid tumors: tumor-associated antigens and the tumor microenvironment.

The past decade has witnessed ongoing progress in immune therapy to ameliorate human health. As an emerging technique, chimeric antigen receptor (CAR) T-cell therapy has the advantages of specific killing of cancer cells, a high remission rate of cancer-induced symptoms, rapid tumor eradication, and long-lasting tumor immunity, opening a new window for tumor treatment. However, challenges remain in CAR T-cell therapy for solid tumors due to target diversity, tumor heterogeneity, and the complex microenvironment. In this review, we have outlined the development of the CAR T-cell technique, summarized the current advances in tumor-associated antigens (TAAs), and highlighted the importance of tumor-specific antigens (TSAs) or neoantigens for solid tumors. We also addressed the challenge of the TAA binding domain in CARs to overcome off-tumor toxicity. Moreover, we illustrated the dominant tumor microenvironment (TME)-induced challenges and new strategies based on TME-associated antigens (TMAs) for solid tumor CAR T-cell therapy.

The Use of Radio and Telemedicine by TMAS Centers in Provision of Medical Care to Seafarers: A Systematic Review.

Objective: From medicine via radio to telemedicine, personalized medical care at sea has improved significantly over the years. Currently, very little research has been conducted on telemedicine services and tools at sea. This study aims to review real-time case studies of seafarers' personalized treatment via telemedical devices published in medical journals. Methods: A literature search was conducted using three libraries such as PubMed (Medline), Cumulative Index to Nursing and Allied Health Literature (CINAHL), BioMed Central, and Google Scholar. The Medical Subject Headings (MeSH) were used for information retrieval and document selection was conducted based on the guidelines of preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 flowchart. Selected articles were subjected to quality checks using the Newcastle-Ottawa scale (NOS). Results: The literature search produced 785 papers and documents. The selection was conducted in three stages such as selection, screening, and inclusion. After applying predefined inclusion and exclusion criteria, only three articles on real-time medical assistance with telemedical tools were identified. It is reported that medical attention is delivered to seafarers in real time thanks to advancements in telemedicine, satellite technology, and video conferencing. Conclusions: By improving the quality of medical care and reducing response times for medical emergencies at sea, lives have been saved. There are still several gaps despite these advancements. Medical assistance at sea should therefore be improved to address many of the still unsolved issues.

Medical treatment of seafarers in the Southern Indian Ocean - interaction between the French Telemedical Maritime Assistance Service (TMAS) and the medical bases of the French Southern and Antarctic Lands (TAAF).

BACKGROUND: The waters surrounding the French Southern Lands are a fishing zone, accessible only by sailing for several days in a region where weather conditions are often difficult. The scientific bases of the region have medical staff whose services can be called upon if seafarers require assessment and rapid medical treatment. We conducted an epidemiological study of the maritime teleconsultations carried out by the French Telemedical Maritime Assistance Service (TMAS), where patients navigating in the Southern Indian Ocean zone were advised to disembark on the medical bases in the French Southern Lands, between 2015 and 2020, to receive medical treatment. MATERIALS AND METHODS: We extracted data from all of the maritime records from 1 January 2015 to 31 December 2020 relating to patients who attended a maritime teleconsultation with a French TMAS doctor in the Southern Indian Ocean zone and who had been redirected to the medical bases in the French Southern Lands. Data were collected on the patients' age, gender, nationality, rank, type of vessel, teleconsultation diagnosis, patient management on board and in the French Southern Lands medical bases, as well as the medical outcome. We carried out a descriptive data analysis. RESULTS: French TMAS doctors managed 11,908 cases including 76 in the Southern Indian Ocean zone (0.6%). Nineteen (25%) patients were redirected to the French Southern Lands over the study period. Eighteen patients were men with an average age of 45 ± 10 years. Eighteen patients were on board a trawler and 11 of them were sailors. Nine patients were treated for a trauma-related condition, 8 for a medical condition and 2 for a surgical disease. Eleven (58%) patients were evacuated to Reunion Island and 8 (42%) patients received medical treatment and were able to re-embark aboard their vessel. CONCLUSIONS: Relatively few patients are redirected to the French Southern Lands for medical assistance, but referrals occur on a regular basis. The presence of these medical bases is unusual in a maritime setting, but they can be a valuable asset when maritime medical assistance is required in this region. The type of condition encountered, and the patient profile, were typical of the fishing community. The presence of these bases and communication between the various stakeholders delivering maritime medical assistance provided these patients with optimal care despite their isolated location.

Quiescin Sulfhydryl Oxidase 2 Overexpression Predicts Poor Prognosis and Tumor Progression in Patients With Colorectal Cancer: A Study Based on Data Mining and Clinical Verification.

Background: As a member of the atypical thiol oxidase family, quiescin sulfhydryl oxidase 2 (QSOX2) has been reported to play an important role in several biological processes, but the expression and function of QSOX2 in colorectal cancer (CRC) remains elusive. Methods: The difference of QSOX2 expression, and its relationship with clinicopathological features and prognosis in CRC, was analyzed by bioinformatic analysis and validated by clinical CRC specimen cohort. The functional characterization of QSOX2 was detected via in vitro and vivo experiments in CRC cell lines, while the potential signaling pathways were predicted by Gene Set Enrichment Analysis (GSEA). Results: Our data based on bioinformatical analysis and clinical validation demonstrated that the expression of QSOX2 in CRC tissues was significantly upregulated. Additionally, the chi-square test, logistic regression analysis, and Fisher's exact test showed that QSOX2 overexpression was significantly correlated with advanced clinicopathological parameters, such as pathological stage and lymph node metastasis. The Kaplan-Meier curves and univariate Cox regression model showed that QSOX2 overexpression predicts poor overall survival (OS) and disease-free survival (DFS) in CRC patients. More importantly, multivariate Cox regression model showed that QSOX2 overexpression could serve as an independent factor for CRC patients. In vitro and vivo data showed that the proliferation and metastasis ability of CRC cells were suppressed on condition of QSOX2 inhibition. In addition, GSEA showed that the QSOX2 high expression phenotype has enriched multiple potential cancer-related signaling pathways. Conclusion: QSOX2 overexpression is strongly associated with malignant progression and poor oncological outcomes in CRC. QSOX2 might act as a novel biomarker for prognosis prediction and a new target for biotherapy in CRC.

Unidirectional Synchronization of Hodgkin-Huxley Neurons With Prescribed Performance Under Transcranial Magneto-Acoustical Simulation.

This paper exploits the unidirectional synchronization dynamics of two Hodgkin-Huxley (HH) neurons under transcranial magneto-acoustical stimulation (TMAS). The major purpose is to explore a control scheme to make the spiking modes of the neural potentials stimulated by TMAS achieve synchronization states under the feedback input. For this purpose, an adaptive neural controller, which makes the neurons satisfy the prescribed master-slaver synchronization performance, is designed by introducing a tracking error into Lyapunov analysis. Under the proposed control scheme, the slaver neuron can not only overcome the model uncertainties and the difficulties brought by prescribed performance, but also track the spiking patterns of the master neuron. Finally, the simulations are implemented to demonstrate the effectiveness of the proposed controller, that is, the TMAS induced synchronization states of the HH neuron system can achieve the prescribed performance under the proposed controller.

An innovative diagnostic strategy for the detection of rare molecular targets to select cancer patients for tumor-agnostic treatments.

Targeted therapies are playing an increasing role in oncology. Among them, particular attention is nowadays reserved to histology-agnostic treatments. Rare molecular alterations affecting different neoplastic forms, such as Microsatellite Instability (MSI), Neurotropic Tyrosine Receptor Kinase (NTRK) gene fusions, etc., can allow efficient treatments, irrespective of the histologic type. Developing an effective testing strategy for the detection of rare molecular alterations is challenging. We report an innovative diagnostic strategy for a rapid and economically affordable detection of this uncommon targets. Malignant tumor samples are selected at the time of histopathological diagnosis and further processed for simultaneous analysis of multiple samples on Tissue Micro Arrays (TMAs) and Tissue Slice Arrays (TSAs). The TSA approach was specifically designed for large scale screening of small biopsies. TMA sections and TSA were first screened by immunohistochemistry (IHC) for the expression of mismatch repair and TRK proteins. Positive cases were subjected to confirmation tests (fragment analysis/FISH/NGS). In a series of 1865 malignant tumors, 48 (2.6%) MSI cases and 6 (0.3%) NTRK fusion cases were detected in 9 and 4 different tumor forms, respectively. On average, the TMA/TSA screening approach enabled IHC analysis of about 20 patients simultaneously with significant saving of time and costs. In addition, we have shown that multiplex IHC can further increment the throughput. A detailed procedure for application of this diagnostic approach in clinical practice is reported. The strategy described may allow an efficient and sustainable selection of tumors carrying rare molecular targets, not to leave behind patients for effective agnostic treatments.

Transcranial Magneto-Acoustic Stimulation Improves Neuroplasticity in Hippocampus of Parkinson's Disease Model Mice.

In this study, we have, for the first time, demonstrated the beneficial effects of transcranial magneto-acoustic stimulation (TMAS), a technique based on focused ultrasound stimulation within static magnetic field, on the learning and memory abilities and neuroplasticity of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). Our results showed that chronic TMAS treatment (2 weeks) improved the outcome of Morris water maze, long-term potentiation (LTP), and dendritic spine densities in the dentate gyrus (DG) region of the hippocampus of PD model mice. To further investigate into the underlying mechanisms of these beneficial effects by TMAS, we quantified the proteins in the hippocampus that regulated neuroplasticity. Results showed that the level of postsynaptic density protein 95 was elevated in the brain of TMAS-treated PD model mice while the level of synaptophysin (SYP) did not show any change. We further quantified proteins that mediated neuroplasticity mechanisms, such as brain-derived neurotrophic factor (BDNF) and other important proteins that mediated neuroplasticity. Results showed that TMAS treatment elevated the levels of BDNF, cAMP response element-binding protein (CREB), and protein kinase B (p-Akt) in the PD model mouse hippocampus, but not in the non-PD mouse hippocampus. These results suggest that the beneficial effects on the neuroplasticity of PD model mice treated with TMAS could possibly be conducted through postsynaptic regulations and mediated by BDNF.

Added value of sending photograph in diagnosing a medical disease declared at sea: experience of the French Tele-Medical Assistance Service.

The maritime medical tele-consultation carried out by a doctor from the Toulouse Tele-Medical Assistance Service is currently based on tele-consultation using radiotelegraphy and the complementary transmission of data (photographs, electrocardiogram) via the Internet. In a previous article, we presented the benefits of photograph transmission for trauma management in isolated areas. Through this new series of cases, we wanted to expose the aspect of the medical pathologies and the contribution of sending photographs in their management. CASE REPORTS: Case 1. Myocardial infarction. Case 2. Toxic epidermal necrolysis. Case 3. Tooth abscess. Case 4. Shingles. Case 5. Junctional tachycardia. The tele-transmission of photographs provides a real diagnostic and follow-up tool for patients suffering from medical pathologies. The constant increase in the number of tele-consultations with the exchange of photographs shows its necessity and the interest of the participants in the development of these technologies.

A Phase-Locking Analysis of Neuronal Firing Rhythms with Transcranial Magneto-Acoustical Stimulation Based on the Hodgkin-Huxley Neuron Model.

Transcranial magneto-acoustical stimulation (TMAS) uses ultrasonic waves and a static magnetic field to generate electric current in nerve tissues for the purpose of modulating neuronal activities. It has the advantage of high spatial resolution and penetration depth. Neuronal firing rhythms carry and transmit nerve information in neural systems. In this study, we investigated the phase-locking characteristics of neuronal firing rhythms with TMAS based on the Hodgkin-Huxley neuron model. The simulation results indicate that the modulation frequency of ultrasound can affect the phase-locking behaviors. The results of this study may help us to explain the potential firing mechanism of TMAS.

Medical emergencies on large passenger ships without doctors: the Oslo-Kiel-Oslo ferry experience.

BACKGROUND: The Oslo-Kiel-Oslo route is currently the only direct ferry crossing between Norway and Germany, covered by 2 cruise-and-cars ferries carrying about 2,600 passengers each and sailing every day (20 h at sea, 4 h in port). Unlike most ocean going cruise vessels, they are not required to carry a physician but an on-board paramedic handles medical emergencies. The aim of the study was to provide data on medical emergencies leading to helicopter evacuations (helivacs) or other urgent transfers to facilities ashore from the two ferries during a 3-year period. MATERIALS AND METHODS: Data about the ferries, passengers, crew, helivacs and other medical transfers were collected from official company statistics and the paramedics' transfer reports. RESULTS: A total of 169 persons, including 14 (8.3%) crewmembers, were transferred from the ferries to land-based facilities by ambulance while alongside (n = 80; 47.3%) or evacuated by helicopter (n = 85; 50.3%) and rescue boat (n = 4; 2.4%) during the 3-year period. Transfer destinations were Denmark (n = 53), Germany (n = 49), Norway (n = 48) and Sweden (n = 19). The passenger helivac rate was 2.4 per 100,000 passenger-days. One person was airlifted from a ferry every 2 weeks. Among helivacs, 40% were heart-related, and more cardiac cases were airlifted than transferred by ambulance in port. CONCLUSIONS: All helivac requests were made after discussion between the ferry's paramedic and telemedical doctors ashore and agreement that the medical challenge exceeded the ferry's capability. This close cooperation kept the threshold for arranging helivacs from the ferries low, enabling short transport times to land-based facilities for critically ill patients. Further studies, including feedback from the receiving hospitals, are needed to determine measures that can reduce possible helicopter overutilisation without compromising patient safety and outcome.

High-Sensitivity IHC Detection of Phosphorylated p27/Kip1 in Human Tissues Using Secondary Antibody Conjugated to Polymer-HRP.

A complex composed of goat anti-rabbit secondary antibody conjugated to a polymer coated with horseradish peroxidase (HRP) molecules was used to develop rapid and highly sensitive immunostaining protocol for the detection of phosphorylated p27/Kip1 (T157) in human tissues. This polymer-HRP complex produced much better sensitivity detection compared to conventional biotin-streptavidin-HRP chemistry. Using polymer-HRP made it possible to reduce primary antibody concentration, eliminate some incubation steps such as avidin-biotin blocking and incubation with separate biotinylated secondary antibodies, and shorten the incubation time with primary antibody. Specificity of the detection was confirmed by eliminating labeling after treating tissues with lambda phosphatase to remove phosphate groups from p27/Kip1. Secondary antibodies conjugated to polymer-HRP is a reagent of choice in both research and diagnostic pathology allowing detecting low abundant and weakly expressed tissue targets.

Effect of ultrasound on some chemical and microbiological properties of sour cherry juice by response surface methodology.

In this study, it is aimed to determine effect of ultrasonication on some chemical and microbiological properties of sour cherry juice by response surface methodology, since ultrasound is known as an alternative method for thermal food processing. Sour cherry juice was sonicated at varying amplitude levels (50, 75, 100%); moderate temperatures (20, 30, 40 ℃); and treatment times of 2, 6, 10 min at a constant frequency of 20 kHz. Different ultrasonication amplitudes, temperatures, and times had no significant effect on pH,°Bx, and titratable acidity. A significant increase in total monomeric anthocyanins was observed as the amplitude level and temperature increased (p < 0.01). An increase in the total phenolics was also obtained as the temperature increased (p < 0.05). The effect of amplitude level on antioxidant capacity of sour cherry juice was also found significant (p < 0.05). Color parameters (L*, a*, b*, C, h) generally increased by increasing temperature, amplitude level, and treatment time. It was determined that Escherichia coli O157:H7 significantly affected by temperature and treatment time (p < 0.05).

Eighty years of CIRM. A journey of commitment and dedication in providing maritime medical assistance.

BACKGROUND: A review of activities of Centro Internazionale Radio Medico (International Radio Medical Centre, CIRM) from its foundation in 1935 until its 80th anniversary in 2015 was accomplished. CIRM was founded in 1935 to provide medical assistance via radio to ships with no doctor on board and other distant patients who cannot be reached by a doctor. In 1950 CIRM was established as a non-profit-making foundation and has benefited since 1957 from an annual contribution from the Italian government. METHODS: Review of CIRM case histories and other published material from 1935 to 2015 and presenting them in a scientific yet simplified manner through the use of basic mathematical analysis. All the data was collected from CIRM's official archives in Rome. RESULTS AND CONCLUSIONS: The results achieved by the Centre over 80 years include medical assistance to 81,016 patients on board ships (as well as on small islands and aircraft), with more than 500,000 medical messages received and transmitted. CIRM from its inception was organised into a medical service, a telecommunications service and a studies section. In 2002 the Centre was recognised as the Italian Telemedical Maritime Assistance Service (TMAS). In the 2010 the Centre was reorganised as a structure articulated in 4 departments, namely maritime telemedicine, telecommunication, research and occupational medicine. This was achieved to cover the different activities related to comprehensive health protection of seafarers. The 24-h continuous medical service is provided by doctors at the CIRM headquarters. The doctor on duty gives instructions for managing the case and continues to follow the patient with subsequent appointments until recovery or landing. In case of emergencies CIRM co-ordinates the transfer of patients assisted on board ships to a hospital ashore. CIRM has developed innovative approaches for the treatment of diseases and accidents on board of seagoing vessels by introducing standard telemedicine equipment on board ships, allowing the transmission of biomedical data from ships to the Centre. These new solutions are aimed at bringing a significant improvement of medical care for seafarers.

Correlation Between the Clinical Parameters and Tissue Phenotype in Patients Affected by Deep-Infiltrating Endometriosis.

The current study aimed to identify and validate an applicable immunohistochemistry panel including Ki-67, c-MYC, estrogen receptor-α (ER-α), and progesterone receptor isoforms A/B (PR-A/B) in correlation with clinicopathological parameters in patients affected by deep infiltrating endometriosis. Tissue microarrays were prepared from a cohort of 113 patients. Phenotypic profile of the panel molecules was evaluated in glands and stroma in parallel with microvessels and stroma density measurements. Principal component analysis was performed on 8 immunohistochemical variables, 2 histological variables, and 8 subgroups of clinical parameters. The immunohistochemical profiling showed consistent Ki-67 immunostaining in 17.9% of the samples and c-MYC in 83.1%, while intense ER-α immunoreactivity was detected in 84% of the samples and PR-A/B isoforms in 24.1% of them. The combination of clinical parameters and tissue phenotype allowed a stratification of endometriosis-affected patients. Such novel phenotypical and clinical correlation could be helpful in the future studies for a better stratification of the disease aiming at a personalized patient care.

Accumulation of tolerogenic human 6-sulfo LacNAc dendritic cells in renal cell carcinoma is associated with poor prognosis.

Dendritic cells (DCs) essentially contribute to the induction and regulation of innate and adaptive immunity. Based on these important properties, DCs may profoundly influence tumor progression in patients. However, little is known about the role of distinct human DC subsets in primary tumors and their impact on clinical outcome. In the present study, we investigated the characteristics of human 6-sulfo LacNAc (slan) DCs in clear cell renal cell carcinoma (ccRCC). slanDCs have been shown to display various tumor-directed properties and to accumulate in tumor-draining lymph nodes from patients. When evaluating 263 ccRCC and 227 tumor-free tissue samples, we found increased frequencies of slanDCs in ccRCC tissues compared to tumor-free tissues. slanDCs were also detectable in the majority of 24 metastatic lymph nodes and 67 distant metastases from ccRCC patients. Remarkably, a higher density of slanDCs was significantly associated with a reduced progression-free, tumor-specific or overall survival of ccRCC patients. Tumor-infiltrating slanDCs displayed an immature phenotype expressing interleukin-10. ccRCC cells efficiently impaired slanDC-induced T-cell proliferation and programming as well as natural killer (NK) cell activation. In conclusion, these findings indicate that higher slanDC numbers in ccRCC tissues are associated with poor prognosis. The induction of a tolerogenic phenotype in slanDCs leading to an insufficient activation of innate and adaptive antitumor immunity may represent a novel immune escape mechanism of ccRCC. These observations may have implications for the design of therapeutic strategies that harness tumor-directed functional properties of DCs against ccRCC.

Different detectability of cyclooxygenase-2 (COX-2) protein in standard paraffin sections and tissue microarrays of human melanomas and naevi - comparative study.

Cyclooxygenase-2 (COX-2), overexpressed in many types of human cancer, may be a valuable marker for human melanoma. However, there are discrepancies between expression levels detected by different groups. The majority of the studies were carried out using standard paraffin sections. Tissue microarrays (TMAs) might enable analysis of COX-2 expression in numerous lesions. Our study assesses to what extent reprocessing of tissue samples used for preparing TMAs may influence reproducibility of data obtained for standard sections. The study included TMAs and standard histopathologic sections. COX-2 was detected by immunohistochemistry with two primary antibodies targeting different epitopes. COX-2 expression levels detected with both antibodies in standard sections were similar as in our previous study. Surprisingly, results obtained in TMAs were significantly different. While one of the antibodies yielded for TMAs results similar to standard sections, COX-2 expression levels found with the second antibody were very low and expression patterns strikingly different from those observed for standard sections and for both TMAs studied with the first antibody. Good performance of the antibodies found in standard sections of human skin and melanocytic lesions does not guarantee similar results in TMAs. The finding discloses a new aspect of immunohistochemical assays involving TMAs.