Noncanonical effector functions of the T-memory-like T-PLL cell are shaped by cooperative TCL1A and TCR signaling.

T-cell prolymphocytic leukemia (T-PLL) is a poor-prognostic neoplasm. Differentiation stage and immune-effector functions of the underlying tumor cell are insufficiently characterized. Constitutive activation of the T-cell leukemia 1A (TCL1A) oncogene distinguishes the (pre)leukemic cell from regular postthymic T cells. We assessed activation-response patterns of the T-PLL lymphocyte and interrogated the modulatory impact by TCL1A. Immunophenotypic and gene expression profiles revealed a unique spectrum of memory-type differentiation of T-PLL with predominant central-memory stages and frequent noncanonical patterns. Virtually all T-PLL expressed a T-cell receptor (TCR) and/or CD28-coreceptor without overrepresentation of specific TCR clonotypes. The highly activated leukemic cells also revealed losses of negative-regulatory TCR coreceptors (eg, CTLA4). TCR stimulation of T-PLL cells evoked higher-than-normal cell-cycle transition and profiles of cytokine release that resembled those of normal memory T cells. More activated phenotypes and higher TCL1A correlated with inferior clinical outcomes. TCL1A was linked to the marked resistance of T-PLL to activation- and FAS-induced cell death. Enforced TCL1A enhanced phospho-activation of TCR kinases, second-messenger generation, and JAK/STAT or NFAT transcriptional responses. This reduced the input thresholds for IL-2 secretion in a sensitizer-like fashion. Mice of TCL1A-initiated protracted T-PLL development resembled such features. When equipped with epitope-defined TCRs or chimeric antigen receptors, these Lckpr-hTCL1Atg T cells gained a leukemogenic growth advantage in scenarios of receptor stimulation. Overall, we propose a model of T-PLL pathogenesis in which TCL1A enhances TCR signals and drives the accumulation of death-resistant memory-type cells that use amplified low-level stimulatory input, and whose loss of negative coregulators additionally maintains their activated state. Treatment rationales are provided by combined interception in TCR and survival signaling.

Carbon tattooing for targeted lymph node biopsy after primary systemic therapy in breast cancer: prospective multicentre TATTOO trial.

BACKGROUND: Several techniques for targeted lymph node biopsy in patients with node-positive breast cancer receiving primary systemic therapy are in use, each with their inherent advantages and disadvantages. The aim of the TATTOO trial was to evaluate the feasibility and accuracy of carbon tattooing of positive lymph nodes as a method for targeted lymph node biopsy avoiding radiation exposure, high costs, and preoperative localization procedures. METHODS: Patients with initially cT1-4c cN1-3 cM0 invasive breast cancer were included in this prospective multicentre trial. Before initiation of primary systemic therapy, a carbon suspension was injected into the most suspicious axillary lymph node. Targeted lymph node biopsy was performed in all patients after completion of primary systemic therapy. Additional sentinel lymph node biopsy was done in those with axillary downstaging, and completion axillary lymph node dissection in patients still presenting with suspicious lymph nodes. RESULTS: A total of 118 patients were included and 110 were eligible for data analysis. The detection rate for the targeted lymph node was 93.6 per cent (103 of 110), and the sentinel lymph node was identical to the targeted lymph node in 60 per cent. The false-negative rate for the combination of targeted and sentinel node lymph node biopsy (targeted axillary dissection) was 9 per cent. CONCLUSION: Targeted axillary dissection after carbon tattooing is associated with a high detection rate, an acceptable false-negative rate, and appears feasible for clinical use even in healthcare settings with limited resources.

Chlorine Isotope Fractionation of the Major Chloromethane Degradation Processes in the Environment.

Chloromethane (CH3Cl) is an important source of chlorine in the stratosphere, but detailed knowledge of the magnitude of its sources and sinks is missing. Here, we measured the stable chlorine isotope fractionation (εCl) associated with the major abiotic and biotic CH3Cl sinks in the environment, namely, CH3Cl degradation by hydroxyl (·OH) and chlorine (·Cl) radicals in the troposphere and by reference bacteria Methylorubrum extorquens CM4 and Leisingera methylohalidivorans MB2 from terrestrial and marine environments, respectively. No chlorine isotope fractionation was detected for reaction of CH3Cl with ·OH and ·Cl radicals, whereas a large chlorine isotope fractionation (εCl) of -10.9 ± 0.7‰ (n = 3) and -9.4 ± 0.9 (n = 3) was found for CH3Cl degradation by M. extorquens CM4 and L. methylohalidivorans MB2, respectively. The large difference in chlorine isotope fractionation observed between tropospheric and bacterial degradation of CH3Cl provides an effective isotopic tool to characterize and distinguish between major abiotic and biotic processes contributing to the CH3Cl sink in the environment. Our findings demonstrate the potential of emerging triple-element isotopic approaches including chlorine to carbon and hydrogen analysis for the assessment of global cycling of organochlorines.

Osteoporosis therapy in patients with inflammatory rheumatic diseases and osteonecrosis of the jaw.

BACKGROUND AND OBJECTIVES: The aim of the present study was to assess the prevalence of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients suffering from inflammatory rheumatic diseases, as well as to assess the prevalence of relevant dental, behavioral, and medical risk factors for MRONJ. MATERIALS AND METHODS: A total of 198 patients with inflammatory rheumatic diseases and osteoporosis therapy were recruited from a tertiary rheumatological/immunological referral center between June 2015 and September 2016. They were assessed using a structured interview. A maxillofacial surgeon later examined patients complaining of possible symptoms of osteonecrosis. In cases of osteonecrosis, dental records were obtained and evaluated. Preventive measures taken and dental as well as other clinical risk factors were evaluated. RESULTS: Of the 198 patients, three suffered from osteonecrosis of the jaw, none of whom had any history of malignant disease or radiation therapy, resulting in a prevalence of 1.5%. Of these three patients, only one was given bisphosphonates intravenously (i.v.), whereas all three had been treated orally. All three diagnoses of MRONJ had been previously known to the patients and their maxillofacial surgeons. Two of the patients had rheumatoid arthritis, and one patient suffered from large vessel vasculitis. Long anti-osteoporotic treatment duration, low functional status, and low bone density of the femur were significantly associated with MRONJ development. CONCLUSION: Inflammatory rheumatic diseases constitute a risk factor for MRONJ in patients treated with bisphosphonates for osteoporosis. Patients should be counseled accordingly and should be offered dental screening and regular dental check-ups.

Identification of Aspergillus and Mucorales in formalin-fixed, paraffin-embedded tissue samples: Comparison of specific and broad-range fungal qPCR assays.

Establishing the etiology of invasive fungal infections is important to guide therapeutic options and for epidemiologic purposes. Formalin-fixed, paraffin-embedded (FFPE) tissue specimens from patients with proven invasive fungal infections are valuable to determine the etiology of systemic fungal infections. We compared different polymerase chain reaction (PCR) amplification strategies from FFPE tissue blocks to identify agents of invasive fungal infections. We found that specific PCR assays show superior sensitivity in the identification of DNA of Mucorales and Aspergillus and mixed infections caused by both as compared to broad-range PCR assays. Shorter amplicon lengths and less detection of contaminating fungal DNA are potential factors involved. However, detection of fungal DNA by highly sensitive specific PCR assays in the absence of demonstration of fungal elements in tissue suggests that PCR results should be interpreted in the context of the histopathology and clinical findings.

[Validation of the German-language version of the Injustice Experience Questionnaire (IEQ) in five outpatient clinics]. / Validierung der deutschen Übersetzung des Injustice Experience Questionnaire (IEQ) in 5 ambulanten Schmerzbehandlungseinrichtungen.

INTRODUCTION: Occupational and social rehabilitation can be influenced by perceived injustice that results from pain. Currently, the Injustice Experience Questionnaire (IEQ), the tool most commonly used to assess perceived injustice, is not available in German. The aim of this study was the validation of the German-language version of the IEQ. MATERIALS AND METHODS: The validation of the IEQ was carried out via a web-based survey. For this purpose, participants completed the IEQ and construct-related scales analogous to the original study Tampa Scale of Kinesiophobia (TSK), Depression scale of the Depression Anxiety and Stress Scales (D-DASS), Pain Disability Index (PDI), and McGill Pain Questionnaire (MPQ). In addition, the participants completed questions on their socioeconomic status and on the cause of their pain, taken from the German Pain Questionnaire. RESULTS: Of 223 respondents, 134 (60.1%) returned a completed questionnaire and were included in the study. In all, 26.1% of participants reported suffering from pain resulting from accidents. None of the reviewed one- to three-factor solutions for the IEQ's structure achieved a good model fit. The best results were found for a two-factor solution, whereby the exploratory factor analysis revealed almost all items loaded highly on both factors and the confirmatory factor analysis showed high correlations between the factors. These findings are consistent with previous studies. The IEQ correlated highly and significantly with the other psychological instruments. There were no floor or ceiling effects. Cronbach's α for the German IEQ version was 0.93 and thus attests a high level of internal consistency. CONCLUSION: The analyses attest the excellent psychometric properties of the German translation of the IEQ and so the German-language version of the IEQ can be used as a validated questionnaire to screen for perceived injustice.

Medical-grade polycaprolactone scaffolds made by melt electrospinning writing for oral bone regeneration - a pilot study in vitro.

BACKGROUND: The spectrum of indications for the use of membranes and scaffolds in the field of oral and maxillofacial surgery includes, amongst others, guided bone regeneration (GBR). Currently available membrane systems face certain disadvantages such as difficult clinical handling, inconsistent degradation, undirected cell growth and a lack of stability that often complicate their application. Therefore, new membranes which can overcome these issues are of great interest in this field. METHODS: In this pilot study, we investigated polycaprolactone (PCL) scaffolds intended to enhance oral wound healing by means of melt electrospinning writing (MEW), which allowed for three-dimensional (3D) printing of micron scale fibers and very exact fiber placement. A singular set of box-shaped scaffolds of different sizes consisting of medical-grade PCL was examined and the scaffolds' morphology was evaluated via scanning electron microscopy (SEM). Each prototype sample with box sizes of 225 µm, 300 µm, 375 µm, 450 µm and 500 µm was assessed for cytotoxicity and cell growth by seeding each scaffold with human osteoblast-like cell line MG63. RESULTS: All scaffolds demonstrated good cytocompatibility according to cell viability, protein concentration, and cell number. SEM analysis revealed an exact fiber placement of the MEW scaffolds and the growth of viable MG63 cells on them. For the examined box-shaped scaffolds with pore sizes between 225 µm and 500 µm, a preferred box size for initial osteoblast attachment could not be found. CONCLUSIONS: These well-defined 3D scaffolds consisting of medical-grade materials optimized for cell attachment and cell growth hold the key to a promising new approach in GBR in oral and maxillofacial surgery.

[Aspects of animal health, animal welfare and biosecurity during 101 transports of piglets in Switzerland]. / Untersuchung von Tiergesundheit, Tierwohl und Biosicherheit während 101 Transporten von Mastferkeln in der Schweiz.

INTRODUCTION: The transfer of piglets is associated with stress for the transported animals. In addition, animal transports are a risk factor for the spread of pathogenic and antibiotic-resistant bacteria and for the introduction of diseases into the herd. In the present study, 101 randomly selected transports of piglets were accompanied from the breeding facility to the pig farm. Parameters related to animal health, animal welfare and biosecurity were assessed. Transported piglets showed signs of abscesses, hernias or cannibalism in 30% and diarrhea or cough in 15% of the cases. The proportion of animals with injuries from conflicts were higher after (15%) than before transport (8%). Suboptimal conditions in regard to density, temperature and lighting were found in 19%, 55% and 36% of the transports. Vehicles were cleaned and disinfected only in 55% of transports before arriving at the breeding facility. Thirty percent of the vehicles were soiled and 20% had already loaded piglets when arriving at the sending facility. Vehicles were neither cleaned nor disinfected in 83% between two piglet transports. Overall, there was a great potential for improvement in animal loading and risk of disease transmission in the investigated piglet transports.

INTRODUCTION: Les transports sont associés à du stress pour les animaux. Ils sont en outre un facteur de risque pour la dissémination de germes pathogènes et antibio-résistants ainsi que pour l'introduction de maladies dans les effectifs d'animaux. Pour la présente étude, on a accompagné 101 transports de porcelets choisis au hasard depuis l'exploitation de production jusqu'à celle d'engraissement. A cette occasion, des paramètres relatifs à la santé des animaux, à leur bien-être et à la biosécurité ont été jugés. Dans environ 30% des cas, des porcelets présentant des abcès, des hernies ou des signes de cannibalisme ont été transportés et dans 15% des cas des animaux souffrant de diarrhée ou de toux. La proportion d'animaux présentant des traces de bagarres était plus élevée de 15% après le transport qu'avant (8%). En ce qui concerne le taux d'occupation, la température et l'éclairage, des carences ont été constatées dans respectivement 19%, 55% et 36% des transports. Les véhicules n'avaient été nettoyés et désinfectés avant leur arrivée dans l'exploitation de production que dans 55% des cas. Trente pour cent des véhicules étaient souillés par des excréments et 20% transportaient déjà des porcelets à leur arrivée sur l'exploitation. Lors de 83% des transports, les véhicules n'ont été ni nettoyés ni désinfectés entre deux transports de porcelets. Il existe un grand potentiel d'amélioration dans les transports de porcelets que nous avons accompagnés, que ce soit du point de vue de l'exposition des animaux au stress ou de la dissémination potentielle de germes.

[German transcultural translation of the Injustice Experience Questionnaire]. / Deutsche transkulturelle Übersetzung des Injustice Experience Questionnaire.

BACKGROUND: Occupational and social rehabilitation is influenced by perceived injustice as a result of injury. To assess perceived injustice, the Injustice Experience Questionnaire (IEQ) has been developed and is available in English. The aim of this study was to translate and culturally adapt the English version of the IEQ into German. MATERIALS AND METHODS: The IEQ was translated into German according to the criteria for the transcultural adaptation of self-assessment tools. The translation was examined in a sample of 19 pain patients as to whether the translated items were comprehensible, unacceptable or offensive, and what their meaning and the reason for the chosen response were. Data were assessed using nonparametric statistical methods. RESULTS: The German translation of the IEQ showed a high degree of comprehensibility. The items' meanings and participants' selected answer options were rated as highly plausible by two raters and the wording of the items was assessed as being neither unacceptable nor offensive by participants. Because of the slightly increased values with regard to Item 3, whose meaning was unrecognized by the raters, the term "Unachtsamkeit" was replaced by "Unaufmerksamkeit." CONCLUSION: The study attests to the cultural and linguistic intelligibility and precision of the German translation of the IEQ. In a follow-up study, the translation should be validated in a larger sample of pain patients.

[Fixed cervical high-grade kyphosis : Chin-on-chest deformity-Treatment plan]. / Die fixierte zervikale hochgradige Kyphose : Chin-to-chest-Deformität ­ Behandlungsstrategie.

BACKGROUND: Surgical correction of severe and rigid cervical kyphosis with chin-on-chest deformity poses significant challenges to both the patient and surgeon once surgery is considered as the treatment of choice. OBJECTIVES: This article presents the current concepts of corrective surgery for patients with severe and rigid cervical kyphosis. MATERIAL AND METHODS: Narrative review and report of clinical experience. RESULTS: The treatment of severe cervical kyphosis indicates a dedicated deformity assessment, the analysis of regional and global imbalance, the identification of spinal sagittal plane compensation mechanisms, detailed radiographic and clinical planning of corrective surgery, and the meticulous performance of surgical correction. Most recent large-scale studies serve as evidence for the benefit of surgical correction and outline the complications that need to be targeted during and after surgery. CONCLUSION: Surgical correction of severe cervical kyphosis can be a pleasant and life-changing event for the disabled patient.

Asymmetric pedicle subtractionosteotomy (aPSO) guided by a 3D-printed model to correct a combined fixed sagittal and coronal imbalance.

Surgical correction of fixed thoracolumbar deformity is usually achieved by estimating the preoperatively planned correction angles during surgery and is therefore prone to inaccuracy. This is particularly problematic in biplanar deformities. To overcome these difficulties, 3D model for planning, preparation, and simulation of an asymmetric pedicle subtraction osteotomy (aPSO) was printed and used to realign coronal and sagittal balance in case of rigid degenerative kyphoscoliosis. A 59-year-old woman presented with severe back pain and spinal claudication and was diagnosed with a rigid kyphoscoliosis with multilevel spinal stenosis. Spino-pelvic parameters were measured preoperatively (pelvic incidence 47° [PI], lumbar lordosis 18° [LL]; pelvic tilt 42° [PT], T1 pelvic angle 40° [TPA], Cobb angle 33°, sagittal vertical axis 10.5 cm [SVA]). To aid the complex deformity in the sagittal and coronal plane, a 1:1 3D model of the spine was printed according to the preoperative computed tomography (CT). With the use of a rebalancing software, the spine was prepared in vitro as a model for intraoperative realignment and the correction was preoperatively simulated. Surgery was accomplished according to the preoperative software-guided plan. Asymmetric pedicle subtraction osteotomy (aPSO) of L3 identical to the 3D model was performed. Additionally, a Smith-Peterson osteotomy of L4/5 with transforaminal lumbar interbody fusion (TLIF) and laminectomy of L2-S1 with pedicle screw instrumentation TH12-S1 was accomplished. Postoperative radiological parameters revealed good success (LL 40°, SVA 6 cm, PT 19°, TPA 22°, and a Cobb angle of 8°). Improvement of the Oswestry disability index (ODI) of 42 to 18, the visual analog scale (VAS) of 8 to 1, and walking distance 100 to 8000 m compared to preoperatively resulted at 24 months follow-up. The precise coronal and sagittal correction of a rigid degenerative kyphoscoliosis presents a major challenge. Asymmetric PSO is able to realign the thoracolumbar spine in both the coronal and sagittal planes. The creation of an in vitro 3D-printed model of a patient's spinal deformity in combination with a software to calculate the correction angles facilitates preoperative planning and implementation of aPSO.

Transoral vertebroplasty of the lateral mass of C1 using image guidance.

BACKGROUND: Osteolytic lesions of the anterior aspects of C1 (lateral mass) are difficult to address in a minimally invasive fashion and are often treated by craniocervical instrumentation. METHODS: We report the feasibility and technical method of transoral vertebroplasty of the lateral mass of the atlas using image guidance and describe the workflow of the procedure. To our knowledge, there has not yet been a technical description of a transoral vertebroplasty using image guidance. RESULTS: Adequate positioning of the pedicle access needle using image guidance for addressing the lateral mass of C1 through a transoral, permuceous access can be achieved. CONCLUSIONS: With the assistance of image guidance, it is safe and feasible to access the lateral mass of the atlas. This constitutes a minimally invasive and fast alternative for introducing the bone needle to C1 rather than using a fluoroscopic device alone.

[Update on nodular lymphocyte predominant Hodgkin's lymphoma and related lesions]. / Update zum nodulären lymphozytenprädominanten Hodgkin-Lymphom und verwandten Läsionen.

The present article gives an overview of novel developments in the diagnosis of nodular lymphocyte predominant Hodgkin's lymphoma with reference to the revised WHO classification from 2016. Differential diagnoses that are discussed are progressively transformed germinal centers, T cell/histiocyte-rich large B cell lymphoma as well as transformation into a diffuse large B cell lymphoma.

Solvent and solute ingress into hydrogels resolved by a combination of imaging techniques.

Using simultaneous neutron, fluorescence, and optical brightfield transmission imaging, the diffusion of solvent, fluorescent dyes, and macromolecules into a crosslinked polyacrylamide hydrogel was investigated. This novel combination of different imaging techniques enables us to distinguish the movements of the solvent and fluorescent molecules. Additionally, the swelling or deswelling of the hydrogels can be monitored. From the sequence of images, dye and solvent concentrations were extracted spatially and temporally resolved. Diffusion equations and different boundary conditions, represented by different models, were used to quantitatively analyze the temporal evolution of these concentration profiles and to determine the diffusion coefficients of solvent and solutes. Solute size and network properties were varied and their effect was investigated. Increasing the crosslinking ratio or partially drying the hydrogel was found to hinder solute diffusion due to the reduced pore size. By contrast, solvent diffusion seemed to be slightly faster if the hydrogel was only partially swollen and hence solvent uptake enhanced.

Cervical arthroplasty with ROTAIO® cervical disc prosthesis: first clinical and radiographic outcome analysis in a multicenter prospective trial.

BACKGROUND: Cervical Disc Arthroplasty (CDA) seems to be an alternative to Anterior Cervical Decompression and Fusion (ACDF) and was developed to minimize the risk of Adjacent Segment Disease (ASD). The ROTAIO Cervical Disc Prosthesis represents a new unconstrained implant with a variable centre of rotation which should enable physiological facet-guided movement. The aim of this current study was to evaluate the clinical outcomes after arthroplasty using ROTAIO Cervical Disc Prosthesis. METHOD: Twenty-seven female and 18 male patients (n = 45) with a mean age of 43.7 ± 7.8 years were prospectively followed up for a maximum of 24 month. Clinical outcomes were assessed by Neck Disability Index (NDI), visual analogue scale (VAS) scores for neck and arm pain, patients´ overall satisfaction and the usage of analgesics. Additionally, radiographic information including ROM of the functional spinal unit (FSU) and signs of adjacent segment disease were recorded. RESULTS: NDI and VAS scores showed significant improvement 6 months after surgery and at last follow-up (p < 0.001). Concerning overall satisfaction 95.7% of the patients showed good to excellent results at the last visit and a significant reduction of analgesic usage was observed (p < 0.001). Radiographic measurements showed a mean increase of ROM up to 8.40° in the treated FSU at last follow-up (p < 0.001). No signs of anterior migration or dislocation of the prosthesis and no subsidence was recorded radiographically. There were no major complications and a low rate of secondary procedures (2.2%). CONCLUSION: In the 24-months follow-up the ROTAIO Cervical Disc Prosthesis provided excellent clinical and radiographical results and seems to be safe and effective for the treatment of symptomatic single-level degenerative disc disease.

Phosphorylated epidermal growth factor receptor expression and KRAS mutation status in salivary gland carcinomas.

OBJECTIVES: Salivary gland carcinomas (e.g., adenoidcystic carcinoma or mucoepidermoid carcinoma) are rare and often unresectable head and neck tumors. They are also weakly affected by most chemotherapeutic drugs, which emphasize the need for further studies on this topic. In clinical practice, various drugs target the well-characterized EGFR pathway in many epithelial tumors. There is limited reliable data on phophorylated EGFR expression, such as activated conformation, in salivary gland tumors. MATERIALS AND METHODS: This study investigates the pEGFR expression in salivary gland carcinomas (n = 43). Three different carcinoma varieties, that represent >50 % of all salivary gland tumors, were included: adenoidcystic carcinoma (n = 23), mucoepidermoid carcinoma (n = 17), and adenocarcinoma NOS (not otherwise specified) (n = 3). The specimens were investigated by immunohistochemistry. Additionally, mutations of KRAS oncogene were screened with gene sequencing. The findings were correlated with clinical data by using SPSS. RESULTS: In 34 out of 43 specimens (79 %), a positive staining for pEGFR was found. Sex, tumor entity, tumor site, and grading had no significant correlation with pEGFR expression. A weak correlation was found for tumor size and pEGFR expression. Significant correlations were found for pEGFR expression with patient's age and lymph node metastasis (pN). No specimen showed a KRAS mutation in codon 12 or 13. CONCLUSION: Salivary gland carcinomas show a high expression of pEGFR. This high expression correlates with lymph node metastasis, which supports the hypothesis that a high pEGFR expression facilitates lymphogenous metastasis. Due to this pEGFR expression, status may be a negative predictive factor in salivary gland carcinoma diagnostics. Patients with pN-positive salivary gland cancer may benefit from EGFR-inhibiting drugs. CLINICAL RELEVANCE: The EGFR pathway may be a potential target for chemotherapy of advanced unresectable salivary gland carcinomas.

[Paratracheal lymph node with suspicion of carcinoma]. / Paratrachealer Knoten mit Karzinomverdacht.

Three paratracheal lymph nodes of a 20-year-old patient were submitted for examination, of which one showed numerous thyrocytes with large void nuclei and was suspected of being metastatic papillary thyroid carcinoma. The simultaneously resected thyroid gland, which was subsequently submitted showed findings consistent with Hashimoto's autoimmune thyroiditis (AIT). In the context of the resected goiter tissue, the suspected lymph node metastasis was identified as a hyperplastic ectopic (so-called parasitic) goiter nodule with thyrocytic changes typically seen in Hashimoto's AIT, such as oxyphilic cell alterations and a high plasma cell content. The re-examination of the suspicious lymph node revealed complete lack of a marginal sinus, thus excluding the diagnosis of a lymph node as well as the diagnosis of thyroid carcinoma metastasis.

[Lymphoma of Ocular and Periocular Tissues - Clinicopathological Correlations]. / Lymphome des peri- und intraokularen Gewebes - klinisch-pathologische Korrelationen.

Lymphomas of the ocular adnexa and intraocular tissue include a wide range of lymphoproliferative neoplastic disorders. They are predominantly extranodal non-Hodgkin lymphomas (NHL). The World Health Organization (WHO) classification of lymphoid neoplasm and individual morphological, immunophenotypical, and molecular genetic features, indicate that they may be divided into B-cell (approximately 80 % of all NHL) and T-cell lymphomas (approximately 10-20 % of all NHL). The most common forms of ocular NHL are extranodal marginal zone lymphoma (EMZL) of the mucosa-associated lymphoid tissue (MALT-type), follicular lymphoma (FL), diffuse large B-cell lymphoma, and mantel cell lymphoma. The clinical signs and symptoms are usually very unspecific and depend on the location, size, and extent of the underlying lymphoma subtype. Typical low grade lymphomas have an indolent clinical course and often remain unrecognized for many years. On the other hand, high grade NHLs, such as DLBCL or MCL, are frequently aggressive, with rapid tumour growth and poor prognosis, despite early detection. Histopathology is still the gold standard in the diagnosis of ocular lymphomas. Basic understanding of the principal pathophysiological and clinical aspects of the development and progression of orbital and ocular lymphomas seems to be mandatory for optimal diagnosis and treatment and for improving survival and prognosis. Both residents in training and board certified ophthalmologists should be aware of these problems.

Therapeutic potential of larval excretory/secretory proteins of the pig whipworm Trichuris suis in allergic disease.

BACKGROUND: Gastrointestinal nematodes are currently being evaluated as a novel therapeutic in the treatment of chronic human inflammatory disorders, due to their unique ability to induce immunoregulatory pathways in their hosts. In particular, administration of ova from the pig whipworm Trichuris suis (T. suis; TSO) has been proposed for the treatment of allergic, inflammatory and autoimmune disorders. Despite these advances, the biological pathways through which TSO therapy modulates the host immune system in the context of human disease remain undefined. METHODS: We characterized the dominant proteins present in the excretory/secretory (E/S) products of first-stage (L1) T. suis larvae (Ts E/S) using LC-MS/MS analysis and examined the immunosuppressive properties of whole larval Ts E/S in vitro and in a murine model of allergic airway disease. RESULTS: Administration of larval Ts E/S proteins in vivo during the allergen sensitization phase was sufficient to suppress airway hyperreactivity, bronchiolar inflammatory infiltrate and allergen-specific IgE production. Three proteins in larval Ts E/S were unambiguously identified. The immunomodulatory function of larval Ts E/S was found to be partially dependent on the immunoregulatory cytokine IL-10. CONCLUSIONS: Taken together, these data demonstrate that the released proteins of larval T. suis have significant immunomodulatory capacities and efficiently dampen allergic airway hyperreactivity. Thus, the therapeutic potential of defined larval E/S proteins should be exploited for the treatment of human allergic disorders.