Search

Chronic wounds remain a therapeutic and financial challenge for physicians and the health care systems. Innovative, inexpensive and effective treatment methods would be of immense value. The sublesional fat grafting could be such treatment, although effectiveness and safety have only been assessed in a few randomised clinical trials. The fat graft was obtained by liposuction, washed with the Coleman method and then injected sublesional and into the wound margins after surgical debridement. For the control group, saline solution was used instead of fat. The primary endpoint was to determine the wound size reduction in both groups. The wounds were measured preoperatively, intraoperatively and 3, 7, 21 and 60 days after the intervention. A p‐value of <0.05 was considered significant. Furthermore, histology and microbiology of the wounds and pain were assessed. A temporary effect of the treatment was observed after 14 and 21 days. The wound size reduction was significantly larger in the intervention group, whereas after 60 days, no significant difference was detected between both groups. No adverse events could be reported and the pain level was almost equal in the control and intervention group. Sublesional fat grafting temporarily enhanced healing of chronic wounds. The procedure was safe and the pain level was low. Repeated interventions could lead to complete wound closure, which should be determined in future studies. [ABSTRACT FROM AUTHOR]

Abstract A case of severe diarrhoea associated with synergistic human bocavirus type 1 (HBoV) and human herpes virus type 6 (HHV6) is reported. The case supports the hypotheses that HBoV infection under clinical conditions may depend on helper viruses, or that HBoV replicates by a mechanism that is atypical for parvoviruses, or that HBoV infection can be specifically treated with cidofovir.

Abstract Background We describe a rare case of diffuse macroscopic discoloration and chemical gastritis due to chronic bromazepam intake. The chemical composition of pharmaceuticals has to be considered at endoscopy and it is evident that some chemical substances damage the epithelial tissue and lead to clinical symptoms. Case Presentation Endoscopy was performed in an 82-year-old patient due to gastroesophageal reflux symptoms and epigastric pain. Gastroscopy showed a hiatal hernia and a scarred duodenal bulb. More striking was the yellow-brownish discoloration of the gastric and the duodenal mucosa. The gastric antrum and the duodenal bulb showed local discoloration that could not be rinsed off. The medical history indicated that bromazepam (6 mg) had been used daily as a sleeping aid in the previous two years. The histopathological findings showed appearances of chemical gastritis. Within the lamina propria and on the epithelial surface there were granules. There was no foreign body reaction to these granules. Corpus mucosa showed a mild chronic gastritis. Conclusions If discoloration of the mucosa at endoscopy is seen, a careful drug history must be sought. This is the first case in literature that shows a chemical gastritis after bromazepam intake.

Background: To date, four human bocaviruses (HBoV) have been described. The most closely related viruses (bovine and canine parvoviruses) are associated with miscarriage in their hosts. The objective of this retrospective study was to determine the frequency of HBoV DNA in miscarriage. Study Design: Tissue samples from 172 patients, in which miscarriage occurred, were included and tested with a published qPCR protocol. Positive PCRs were mutually confirmed by sequencing. Results: 43 patients (25%) were positive for HBoV DNA. Of those, the majority of HBoV‐positive samples were tissues from miscarriage (placenta: 6; aborted tissue products of conception: 37 specimens). The samples were not paired; either placental or aborted tissue was available. Conclusions: The results show that, as long as no animal model is available, the role of HBoV in the occurrence of miscarriage requires additional prospective studies in order to investigate its significance and causal involvements of this pathogen. [ABSTRACT FROM AUTHOR]

Background: The human bocavirus (HBoV) is known to persist latently in the infected host cells and seems to replicate its DNA via the DNA damage response system, which is frequently defect in tumors and correlates with microsatellite instability (MSI). Because HBoV is able to persist in the infected tissues, induces pro-fibrotic and pro- cancerogenic cytokines in vivo and in vitro , and is detected in colorectal and lung tumors, the virus may be involved in cancerogenesis at least as a cofactor. Recently it was shown that the adenotonsillar tissue is an important site of HBoV1 persistence and replication. Considering the background that approximately 60% of oropharyngeal cancers were thought to be attributable to a HPV infection, a co-participation of HBoV in terms of a chronic virus infection might play a role in the cancerogenesis of tonsil tumors. Methods: Formalin-fixed, paraffin-embedded tonsil tumor samples were screened for HBoV and HPV DNA. Positive tissue sections were afterward subjected to fluorescence in situ hybridization (FISH) analysis to identify HBoV and HPV infected cells. By use of an in vitro cell culture model with primary tonsil fibroblasts, keratinocytes, and lymphocytes infected by HBoV we tried to find the target cells of virus replication. MSI testing was based on a previously published protocol using a de-multiplexed PCR followed by fluorescent detection of PCR products in a capillary sequencing device. Results: In total 62 of 103 (60, 19%) of the tonsil squamous cell carcinomas tested positive for HBoV DNA and 66 of 103 (66%) samples were identified as HPV positive. The FISH analysis revealed both double infection of HPV and HBoV in the same cells as well as single infections of both viruses within the tumor tissue. Twenty-two of 62 HBoV positive tumors tested HPV negative, 40 of 62 tissue sections were HBoV and HPV positive. We analyzed 21 out of the 62 HBoV positive tumors for MSI. Of those four tonsils displayed MSI in at least 1 of 10 microsatellite markers. Conclusion: Our findings support the hypothesis that human bocavirus infections as a cofactor may have an impact on tumor development in tonsils, although it still remains possible that HBoV solely displays a tumor tropism. [ABSTRACT FROM AUTHOR]

Aim: In this study, the novel VisionArray HPV assay was compared with the LCD CHIP array for the detection of HPVs in tonsillar carcinoma. Materials & methods: A Panel of tonsillar tumors and control samples containing know HPV isolates were tested with the VisonArry HPV Assay (Zytovision, Bremerhaven, Germany) and the Chipron MycoDirect LCD Assay (Chipron, Berlin, Germany). Results: While both assays enabled the discrimination between low-risk, intermediate and high-risk types, the LCD CHIP assay had a better laboratory performance and was more comfortable in its usage. However, both arrays delivered comparable results. Conclusion: Both assays are appropriate tools for the detection of clinically relevant HPV strains in tonsillar tumors. However, if the LCD CHIP array is established, the more complex workflow required for the VisionArray HPV assay could restrain diagnostic labs from a change to this novel assay despite its good quality. [ABSTRACT FROM AUTHOR]

Despite an increasing number of molecular biomarkers identified in non-small cell lung cancer (NSCLC), the number of approved therapy options targeting these biomarkers remains limited. Although some biomarkers may influence the therapy outcome of a distinct drug and have been shown to be useful in phase 2 or 3 clinical studies, diagnostics of biomarkers without an approved drug available or a possible off-label use is currently too expensive for routine diagnostics in non-academic institutions. For this reason, the present review is intended to summarize the current state of the art of molecular diagnostics that is both available and could lead to therapy guidance in NSCLC courses. Thereby, economic aspects are taken into account in order to take up the cudgels for a more comprehensive, even if more expensive, diagnostic scheme that in turn may save enormous costs by reducing therapy costs. [ABSTRACT FROM AUTHOR]

With an incidence of 68 new cases per 100,000 people per year, an estimated total number of up to 350,000 new non-small-cell lung cancer (NSCLC) cases are diagnosed each year in the European Union. Up to 10% of NSCLC patients are eligible for therapy with novel ALK (anaplastic lymphoma kinase) inhibitors, as they have been diagnosed with a mutation in the gene coding for ALK. The ALK inhibitor therapy costs add up to approx. 9000 € per patient per month, with treatment durations of up to one year. Recent studies have shown that up to 10% of ALK cases are misdiagnosed by nearly 40% of pathologic investigations. The current state-of-the-art ALK diagnostic procedure comprises a Fluorescent in situ Hybridization (FISH) assay accompanied by ALK inhibitor therapy (Crizotinib). The therapy success ranges between a full therapy failure and the complete remission of the tumor (i.e., healing), but the biomedical and systemic reasons for this range remain unknown so far. It appears that the variety of different ALK mutations and variants contributes to the discrepancy in therapy results. Although the major known fusion partner for ALK in NSCLC is the Echinoderm microtubule-associated protein-like 4 (EML4), of which a minimum of 15 variants have been described, an additional 20 further ALK fusion variants with other genes are known, of which three have already been found in NSCLC. We hypothesize that the wide variety of known (and unknown) ALK mutations is associated with a variable therapy success, thus rendering current companion diagnostic procedures (FISH) and therapy (Crizotinib) only partly applicable in ALK-related NSCLC treatment. In cell culture, differing sensitivity to Crizotinib has been shown for some fusion variants, but it is as yet unknown which of them are really biologically active in cancer patients, and how the respective variants affect the response to Crizotinib treatment. Moreover, it has been demonstrated that translocated ALK genes can also be observed in healthy tissues and are not compulsorily associated with tumors. Therefore, it is important to keep in mind that even for the known variants of ALK fusion genes, the biological function is not known for all variants, and that no information is available on the homogeneity of ALK fusion variants within a single tumor. These facts, in concert with data for ALK mutation prevalence and therapy outcomes of a German cohort of NSCLC patients, support the hypothesis that, by using novel companion diagnostic tools in combination with therapy outcome predictions, massive cost savings could be possible in European Health Care systems without a loss of patient care. [ABSTRACT FROM AUTHOR]

Human Bocavirus subtype 1 (HBoV1) is associated with respiratory diseases and may contribute to chronic lung diseases by persisting in the infected host. Here the question was addressed if HBoV infections could contribute to fibrogenesis processes as suggested by previously published clinical observations. Cytokine profiles induced by HBoV infection in CuFi-8 air-liquid interphase cell cultures and in bronchoalveolar lavage fluid (BALF) of 20 HBoV-positive and 12 HBoV-negative patients were analysed by semi-quantitative Western spot blot analyses. Although lots of cytokines were regulated independently of HBoV status, several cytokines associated with lung fibrosis and tumour development, e.g., EGF, VEGF, TARC (CCL17), TNF-α, TNF-β, TIMP-1, were clearly upregulated in the HBoV-positive cohort. These findings suggest that the development of lung fibrosis might be triggered by HBoV induced cytokine expression. [ABSTRACT FROM AUTHOR]

Introduction: Spontaneous regression of cancer is defined as a complete or partial, temporary or permanent disappearance of tumor in the absence of specific therapy. With only a few cases reported, spontaneous regression is extremely rare in primary lung cancer. Regarding spontaneous regression in lung cancer, recent investigations revealed the role of immunological mechanisms, thus indicating potential treatment options by specific immunotherapy in the future.Case Presentation: A 76-year-old Caucasian man with progressive dyspnea presented to our hospital. A computed tomography scan revealed a tumor mass in the upper lobe of his right lung and enlarged mediastinal lymph nodes. A biopsy of a paratracheal lymph node by mediastinoscopy disclosed metastatic lung cancer. By immunohistochemical findings the tumor was classified as large cell carcinoma. Diagnosed with clinical stage IIIA non-small cell lung cancer, a neoadjuvant therapy concept was indicated. However, before starting chemoradiation, a computed tomography scan showed a regression of both the tumor mass in the upper lobe of his right lung and the mediastinal lymphadenopathy. As a repeated computed tomography scan showed further regression, we agreed with our patient to perform routine follow-up instead of starting therapy. To date, no relapse has been reported.Conclusions: Given the circumstances that regression started after the biopsy and involved both the tumor in the upper lobe of his right lung and the mediastinal lymph node metastases, an immune response is a reasonable explanation for the observed spontaneous regression in this case. [ABSTRACT FROM AUTHOR]

Crizotinib, a selective tyrosine kinase inhibitor (TKI), shows marked activity in patients whose lung cancers harbor fusions in the gene encoding anaplastic lymphoma receptor tyrosine kinase (ALK), but its efficacy is limited by variable primary responses and acquired resistance. In work arising from the clinical observation of a patient with ALK fusion-positive lung cancer who had an exceptional response to an insulin-like growth factor 1 receptor (IGF-1R)-specific antibody, we define a therapeutic synergism between ALK and IGF-1R inhibitors. Similar to IGF-1R, ALK fusion proteins bind to the adaptor insulin receptor substrate 1 (IRS-1), and IRS-1 knockdown enhances the antitumor effects of ALK inhibitors. In models of ALK TKI resistance, the IGF-1R pathway is activated, and combined ALK and IGF-1R inhibition improves therapeutic efficacy. Consistent with this finding, the levels of IGF-1R and IRS-1 are increased in biopsy samples from patients progressing on crizotinib monotherapy. Collectively these data support a role for the IGF-1R-IRS-1 pathway in both ALK TKI-sensitive and ALK TKI-resistant states and provide a biological rationale for further clinical development of dual ALK and IGF-1R inhibitors. [ABSTRACT FROM AUTHOR]

Stem cells have been demonstrated to possess a therapeutic potential in experimental models of various central nervous system disorders, including stroke. The types of implanted cells appear to play a crucial role. Previously, groups of the stem cell network NRW implemented a feeder-based cell line within the scope of their projects, examining the implantation of stem cells after ischemic stroke and traumatic brain injury. Retrospective evaluation indicated the presence of spindle-shaped cells in several grafts implanted in injured animals, which indicated potential contamination by co-cultured feeder cells (murine embryonic fibroblasts - MEFs). Because feeder-based cell lines have been previously exposed to a justified criticism with regard to contamination by animal glycans, we aimed to evaluate the effects of stem cell/MEF co-transplantation. MEFs accounted for 5.3-2.8% of all cells in the primary FACS-evaluated co-culture. Depending on the culture conditions and subsequent purification procedure, the MEF-fraction ranged from 0.9 to 9.9% of the cell suspensions in vitro. MEF survival and related formation of extracellular substances in vivo were observed after implantation into the uninjured rat brain. Impurity of the stem cell graft by MEFs interferes with translational strategies, which represents a threat to the potential recipient and may affect the graft microenvironment.The implications of these findings are critically discussed. [ABSTRACT FROM AUTHOR]

A total of three cases with novel constellations regarding mutation patterns in non-small-cell lung cancer (NSCLC) are reported. The mutation patterns that are observed are novel and unexpected. First, a combined simultaneous KRAS mutation and EML4-ALK translocation, both in the main tumor and a bone metastasis, were observed, these mutations are assumed to mutually exclude each other. A further two cases include a father and a daughter, both of whom are suffering from NSCLC with different EGFR mutation patterns. A common cause was assumed; however, could not be deduced to mutations in the KRAS, BRAF and EGFR genes. The aforementioned cases are important, as it must be taken into account that mutations previously assumed to be exclusive can occur in combination, may influence the clinical outcome and may require different therapy compared with single mutated tumors. It has to be discussed whether diagnostic algorithms need to be adapted. The cases of father and daughter show that further unknown factors can influence development of NSCLC. [ABSTRACT FROM AUTHOR]

Copyright of Forensische Psychiatrie, Psychologie, Kriminologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We consider a simple integrable model of a spin chain exhibiting the magnetoelectric effect (MEE). Starting from the periodic 5=1/2 XXZ chain with Dzyaloshinskii-Moriya terms, which we consider as a local electric polarization in the spirit of the Katsura-Nagaosa-Baladsky (KNB) mechanism, we perform the mapping onto the conventional XXZ chain with twisted boundary conditions. Using the techniques of quantum transfer matrix and nonlinear integral equations we obtain the magnetization, electric polarization, and magnetoelectric tensor as functions of magnetic and electric field for arbitrary temperatures. We investigate these dependencies as well as the thermal behavior of the above-mentioned physical quantities, especially in the low-temperature regime. We found several regimes of polarization. Adjusting the magnetic field one can switch the system from one regime to another. The features of the critical properties connected with the MEE are also illustrated. [ABSTRACT FROM AUTHOR]

We analyze the absorption of microwaves by the Heisenberg-Ising chain combining exact calculations, based on the integrability of the model, with numerical calculations. Within linear response theory, the absorbed intensity is determined by the imaginary part of the dynamical susceptibility. The moments of the normalized intensity can be used to define the shift of the resonance frequency induced by the interactions and the linewidth independently of the shape of the spectral line. These moments can be calculated exactly as functions of temperature and strength of an external magnetic field, as long as the field is directed along the symmetry axis of the chain. This allows us to discuss the linewidth and the resonance shift for a given magnetic field in the full range of possible anisotropy parameters. For the interpretation of these data, we need a qualitative knowledge of the line shape, which we obtain from fully numerical calculations for finite chains. Exact analytical results on the line shape are out of reach of current theories. From our numerical work, we could extract, however, an empirical parameter-free model of the line shape at high temperatures, which is extremely accurate over a wide range of anisotropy parameters, and is exact at the free-fermion and isotropic points. Another prediction of the line shape can be made in the zero-temperature and zero magnetic field limits, where the sufficiently anisotropic model shows strong absorption. For anisotropy parameters in the massive phase, we derive the exact two-spinon contribution to the spectral line. From the intensity sum rule, it can be estimated that this contribution accounts for more than 80% of the spectral weight if the anisotropy parameter is moderately above its value at the isotropic point. [ABSTRACT FROM AUTHOR]

Benign cystic mesothelioma is a rare pathology predominantly encountered in females. The increased use of laparoscopy for abdominal pain, particularly in female patients, implies that surgeons are aware of the macro- and laparoscopic presentation of this tumor for adequate diagnosis and therapy. In this paper, we present the case of a young woman with benign multicystic mesothelioma in which only laparoscopy led to the appropriate diagnosis. Subsequently, the tumor was removed by laparoscopic surgery. [ABSTRACT FROM AUTHOR]

Lung and colorectal cancers (CRC) have two of the highest mortality rates among all cancer types, and their occurrence and the need for personalized diagnostics and subsequent therapy were not influenced by the COVID-19 pandemics. However, due to the disruption of established delivery chains, standard assays for in vitro diagnostics of those cancers were temporarily not available, forcing us to implement alternative testing methods that enabled at least basic therapy decision making. For this reason, we evaluated rapid testing on the Biocartis Idylla™ platform (Biocartis, Mechelen, Belgium) for four important genes commonly mutated in lung and colorectal cancers, namely EGFR, NRAS, KRAS, and BRAF. Clinical specimens from which the mutation status has previously been determined using Next Generation Sequencing (NGS), were retested to determine whether Idylla™ can offer accurate results. To compare the results, the sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) are calculated for each of the mutation types and then combined to determine the values of the Idylla™ system in total, while setting NGS as the gold-standard basis the assays were compared with. Idylla testing thereby displayed acceptable sensitivity and specificity and delivered reliable results for initial therapy decisions. [ABSTRACT FROM AUTHOR]

Background: Mesothelioma (MPM) is a rare malignant disease with a worse outcome. Fibroblast growth factor 1 (FGFR1) may be an interesting target for selective tyrosine kinases inhibitors (TKI) in MPM. The aim of this study was to evaluate the amplification of the FGFR1 gene in patients suffering from MPM. Findings: We identified nineteen male patients treated in our department between August 2008 and July 2010 matching the inclusion criteria. Mean age was 68 years. Histopathological examination confirmed thirteen patients with epitheloid subtype, five with biphasic and one patient with sarcomatoid. Fluorescence in situ hybridization analysis revealed no polysomy nor an amplification of the FGFR gene copy number in any case. Conclusion: Regarding that also EGFR amplifications in MPM are absolute rarities, our findings may be a hint that TKI's will not satisfy the hope for a new era in the treatment of MPM. [ABSTRACT FROM AUTHOR]

Background: We describe a rare case of diffuse macroscopic discoloration and chemical gastritis due to chronic bromazepam intake. The chemical composition of pharmaceuticals has to be considered at endoscopy and it is evident that some chemical substances damage the epithelial tissue and lead to clinical symptoms. Case Presentation: Endoscopy was performed in an 82-year-old patient due to gastroesophageal reflux symptoms and epigastric pain. Gastroscopy showed a hiatal hernia and a scarred duodenal bulb. More striking was the yellow-brownish discoloration of the gastric and the duodenal mucosa. The gastric antrum and the duodenal bulb showed local discoloration that could not be rinsed off. The medical history indicated that bromazepam (6 mg) had been used daily as a sleeping aid in the previous two years. The histopathological findings showed appearances of chemical gastritis. Within the lamina propria and on the epithelial surface there were granules. There was no foreign body reaction to these granules. Corpus mucosa showed a mild chronic gastritis. Conclusions: If discoloration of the mucosa at endoscopy is seen, a careful drug history must be sought. This is the first case in literature that shows a chemical gastritis after bromazepam intake. [ABSTRACT FROM AUTHOR]

The article focuses on the contrast-enhanced computed tomography of the chest of a 62-year-old man diagnosed with glioblastoma multiforme and currently under chemoradiation therapy presented with massive haemoptysis showing the pseudoaneurysm of the right upperlobe pulmonary artery.