Study protocol: fish oil supplement in prevention of oxaliplatin-induced peripheral neuropathy in adjuvant colorectal cancer patients - a randomized controlled trial. (OxaNeuro).

BACKGROUND: Oxaliplatin-induced peripheral neuropathy (OIPN) in general and painful OIPN in particular is a debilitating late effect that severely affects cancer survivors' quality of life and causes premature cessation of potentially lifesaving treatment. No preventive treatments and no effective treatment for chronic OIPN exist despite many attempts. One of several suggested mechanisms includes neuroinflammation as a contributing factor to OIPN. Fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFAs) are precursors to specialized proresolving mediators that mediate the resolution of inflammation. Our primary hypothesis is that a high supplementation of n-3 LCPUFAs will lower the prevalence and severity of OIPN. METHODS: The OxaNeuro project is an investigator-initiated, multicenter, double-blinded, randomized, placebo-controlled clinical study. We will include 120 patients eligible to receive adjuvant oxaliplatin after colorectal cancer surgery. Patients will receive fish oil capsules containing n-3 LCPUFAs or corn oil daily for 8 months. The primary endpoint is the prevalence of OIPN at 8 months defined as relevant symptoms, including one of the following: abnormal nerve conduction screening, abnormal vibration threshold test, abnormal skin biopsy, or abnormal pinprick test. Additional endpoints include the intensity and severity of OIPN-related neuropathic pain, patient-reported OIPN symptoms, quality of life, mental health symptoms, body composition, and cognitive evaluation. Furthermore, we will evaluate inflammatory biomarkers in blood samples and skin biopsies, including the potential OIPN biomarker neurofilament light protein (NfL) which will be measured before each cycle of chemotherapy. DISCUSSION: If readily available fish oil supplementation alleviates OIPN prevalence and severity, it will significantly improve the lives of both cancer survivors and palliative cancer patients receiving oxaliplatin; it will improve their quality of life, optimize chemotherapeutic treatment plans by lowering the need for dose reduction or premature cessation, and potentially increase survival. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT05404230 Protocol version: 1.2, April 25th. 2023.

Nuclear import of BCL11B is mediated by a classical nuclear localization signal and not the Krüppel-like zinc fingers.

The Krüppel-like transcription factor (KLF) BCL11B is characterized by a wide tissue distribution and crucial functions in key developmental and cellular processes, as well as in various pathologies including cancer and HIV infection. Although the basics of BCL11B activity and relevant interactions with other proteins have been uncovered, how this exclusively nuclear protein localizes to its compartment remained unclear. Here, we demonstrate that unlike other KLFs, BCL11B does not require the C-terminal DNA-binding domain to pass through the nuclear envelope but has an independent, previously unidentified, nuclear localization signal (NLS), which is located distantly from the zinc finger domains and fulfills the essential criteria of being an autonomous NLS. First, it can redirect a heterologous cytoplasmic protein to the nucleus. Second, its mutation causes aberrant localization of the protein of origin. Finally, we provide experimental and in silico evidences of the direct interaction with importin-α. The relative conservation of this motif allows formulating a consensus sequence (K/R)K-X13-14-KR+K++ ('+' indicates amino acids with similar chemical properties), which can be found in all BCL11B orthologs among vertebrates and in the closely related protein BCL11A.

Reliability of Medical Information Provided by ChatGPT: Assessment Against Clinical Guidelines and Patient Information Quality Instrument.

BACKGROUND: ChatGPT-4 is the latest release of a novel artificial intelligence (AI) chatbot able to answer freely formulated and complex questions. In the near future, ChatGPT could become the new standard for health care professionals and patients to access medical information. However, little is known about the quality of medical information provided by the AI. OBJECTIVE: We aimed to assess the reliability of medical information provided by ChatGPT. METHODS: Medical information provided by ChatGPT-4 on the 5 hepato-pancreatico-biliary (HPB) conditions with the highest global disease burden was measured with the Ensuring Quality Information for Patients (EQIP) tool. The EQIP tool is used to measure the quality of internet-available information and consists of 36 items that are divided into 3 subsections. In addition, 5 guideline recommendations per analyzed condition were rephrased as questions and input to ChatGPT, and agreement between the guidelines and the AI answer was measured by 2 authors independently. All queries were repeated 3 times to measure the internal consistency of ChatGPT. RESULTS: Five conditions were identified (gallstone disease, pancreatitis, liver cirrhosis, pancreatic cancer, and hepatocellular carcinoma). The median EQIP score across all conditions was 16 (IQR 14.5-18) for the total of 36 items. Divided by subsection, median scores for content, identification, and structure data were 10 (IQR 9.5-12.5), 1 (IQR 1-1), and 4 (IQR 4-5), respectively. Agreement between guideline recommendations and answers provided by ChatGPT was 60% (15/25). Interrater agreement as measured by the Fleiss κ was 0.78 (P<.001), indicating substantial agreement. Internal consistency of the answers provided by ChatGPT was 100%. CONCLUSIONS: ChatGPT provides medical information of comparable quality to available static internet information. Although currently of limited quality, large language models could become the future standard for patients and health care professionals to gather medical information.

Prevention of conversion in posterior retroperitoneal adrenalectomy by measuring pre-operative anatomical conditions on cross-sectional imaging (computerised tomography or magnetic resonance imaging).

Background: In addition to the common laparoscopic lateral transperitoneal adrenalectomy (LTA), the posterior retroperitoneal adrenalectomy (PRA) is becoming increasingly important. Both techniques overlap in their indication, resulting in uncertainty about the preferred approach in some patients. We hypothesise that by determining anatomical characteristics on cross-sectional imaging computerised tomography or magnetic resonance imaging, we can show the limitations of the PRA and prevent patients from being converted to LTA. Methods: This retrospective study includes 14 patients who underwent PRA (n = 15) at a single institution between 2016 and 2018. Previously described parameters such as the retroperitoneal fat mass (RPF) were measured on pre-operative imaging. We compared data from one patient who had a conversion with those from 13 patients without conversion. Furthermore, we explored the influence of these parameters on the operative time. Results: Conversion to LTA was necessary during 1 PRA procedure. Fourteen PRAs in 13 patients were successfully completed. The mean body mass index was 30 kg/m2 and the mean operation time was 98 min. One patient who underwent a conversion had a substantially higher RPF (25 mm) compared to the patients with successfully completed PRA (median: 5.5 mm [P = 0.001]). Furthermore, the operation time strongly correlated with the RPF (P = 0.004, r = 0.713). Conclusions: Surgeons can use pre-operative imaging to assess the anatomical features to determine whether a PRA can be performed. Patients with an RPF under 14.3 mm can be safely treated with PRA. In contrast, LTA access should be considered for patients with a higher RPF (>25 mm).

Near-infrared autofluorescence of the parathyroid glands during thyroidectomy for the prevention of hypoparathyroidism: a prospective randomized clinical trial.

PURPOSE: Postoperative hypoparathyroidism remains the most often complication in thyroid surgery. Near-infrared autofluorescence (NIR-AF) is a modality to identify parathyroid glands (PG) in vivo with high accuracy, but its use in daily routine surgery is unclear so far. In this randomized controlled trial, we evaluate the ability of NIR-AF to prevent postoperative hypoparathyroidism following total thyroidectomy. METHODS: Patients undergoing total thyroidectomy were allocated in two groups with the use of NIR-AF in the intervention group or according to standard practice in the control group. The aim was to identify the PGs in an early most stage of the operation to prevent their devascularization or removal. Parathyroid hormone was measured pre- and postoperatively and on postoperative day (POD) 1. Serum calcium was measured on POD 1 and 2. Possible symptoms and calcium/calcitriol supplement were recorded. RESULTS: A total of 60 patients were randomized, of whom 30 underwent NIR-AF-based PG identification. Hypoparathyroidism at skin closure occurred in 7 out of 30 patients using NIR-AF, respectively, in 14 out of 30 patients in the control group (p=0.058). There was no significant difference in serum calcium and parathyroid hormone levels between both groups. Likewise, NIR-AF could not detect PGs at a higher rate. CONCLUSION: The use of NIR-AF may help surgeons identify and preserve PGs but did not significantly reduce the incidence of postoperative hypoparathyroidism in this trial. Larger case series have to clarify whether there is a benefit in routine thyroidectomy. TRIAL REGISTRATION NUMBER: DRKS00009242 (German Clinical Trial Register). Registration date: 03.09.2015.

Development of the German social attitude barriers and facilitators to participation-scales: an analysis according to the Rasch model.

BACKGROUND: Social attitudes experienced by people with disabilities can strongly impact upon their health and quality of life. The extent to which social attitude measurement transcends specific cultures is unknown. Thus, the aim of the study was to develop German item banks to assess social attitude barriers and facilitators to participation and compare the construct definition with that developed in the United States. METHODS: The American version of the two item banks assessing social attitudes that act as barriers and facilitators in persons with disabilities was translated into German and culturally adapted. The sample consisted of 410 in- and outpatients treated for spinal diseases at a German University Hospital. The psychometric properties of the resulting 53 items-item pool were evaluated using Rasch analysis. A special focus was placed on the investigation of unidimensionality, local independence, differential item functioning (DIF) and targeting. To evaluate convergent and divergent validity correlations with perceived social support, depression and pain interference were calculated. RESULTS: Unlike the American version, both the barriers and facilitators item banks had to be divided into two subscales assessing attitudes that individuals with disabilities experience as being directed towards them (individual perception) or attitudes that respondents experience as being directed towards people with disabilities as a social group (societal perception). Four unidimensional scales were constructed. Fit to the Rasch model required item deletion and forming testlets to account for extensive local dependence. There was no evidence of DIF with regard to gender or age. Targeting of the subscales was moderate to good. CONCLUSIONS: Results support a distinction between social attitudes at the individual and societal level, allowing a more specific assessment than is possible when this distinction is ignored.

Clonal dynamics in a composite chronic lymphocytic leukemia and hairy cell leukemia-variant.

Composite lymphoma is the rare simultaneous manifestation of two distinct lymphomas. Chronic lymphocytic leukemia (CLL) has a propensity for occurring in composite lymphomas, a phenomenon that remains to be elucidated. We applied cytogenetics, droplet digital polymerase chain reaction, and massively parallel sequencing to analyze longitudinally a patient with CLL, who 3 years later showed transformation to a hairy cell leukemia-variant (HCL-V). Outgrowth of the IGHV4-34-positive HCL-V clone at the expense of the initially dominant CLL clone with trisomy 12 and MED12 mutation started before CLL-guided treatment and was accompanied by a TP53 mutation, which was already detectable at diagnosis of CLL. Furthermore, deep sequencing of IGH showed a composite lymphoma with presence of both disease components at all analyzed timepoints (down to a minor clone: major clone ratio of ~1:1000). Overall, our analyses showed a disease course that resembled clonal dynamics reported for malignancies with intratumoral heterogeneity and illustrate the utility of deep sequencing of IGH to detect distinct clonal populations at diagnosis, monitor clonal response to therapy, and possibly improve clinical outcomes.

Comparison of inpatient and outpatient palliative sedation practice - A prospective observational study.

INTRODUCTION: Palliative sedation (PS) is an intrusive measure to relieve patients at the end of their life from otherwise untreatable symptoms. Intensive discussion of the advantages and limitations of palliative care with the patients and their relatives should precede the initiation of PS since PS is terminated by the patient's death in most cases. Drugs for PS are usually administered intravenously. Midazolam is widely used, either alone or in combination with other substances. PS can be conducted in both inpatient and outpatient settings; however, a quality analysis comparing both modalities was missing so far. PATIENTS AND METHODS: This prospective observational study collected data from patients undergoing PS inpatient at the palliative care unit (PCU, n = 26) or outpatient at a hospice (n = 2) or at home (specialized outpatient palliative care [SAPV], n = 31) between July 2017 and June 2018. Demographical data, indications for PS, and drug protocols were analyzed. The depth of sedation according to the Richmond Agitation Sedation Scale (RASS) and the degree of satisfaction of staff members and patient's relatives were included as parameters for quality assessment. RESULTS: Patients undergoing PS at the PCU were slightly younger compared to outpatients (hospice and SAPV combined). Most patients suffered from malignant diseases, and midazolam was the backbone of sedation for inpatients and outpatients. The median depth of sedation was between +1 and -3 according to the RASS with a trend to deeper sedation prior to death. The median degree of satisfaction was "good," scored by staff members and by patient's relatives. Significant differences between inpatients and outpatients were not seen in protocols, depth of sedation, and degree of satisfaction. CONCLUSION: The data support the thesis that PS is possible for inpatients and outpatients with comparable results. For choosing the best place for PS, other aspects such as patient's and relative's wishes, stress, and medical reasons should be considered.

Can Isoflavones Influence Prostate Specific Antigen Serum Levels in Localized Prostate Cancer? A Systematic Review.

Low risk prostate cancer does not always necessitate aggressive or invasive intervention and is best monitored through active surveillance, but in daily practice a majority of men seek a more proactive approach. Therefore, tertiary chemoprevention is an attractive option for men seeking a way to slow disease progression. Several natural anti-carcinogens have been identified in soy beans, especially isoflavones. Case series have been published, demonstrating a positive influence of isoflavones on PSA serum levels in prostate cancer. Consequently, we decided to perform a systematic review about the effect of isoflavones compared to placebo on PSA levels in localized prostate cancer following the recommendations provided in the Cochrane Handbook of systematic Reviews. On the whole, the primary aim of this review is to summarize the evidence for the use of isoflavones in localized prostate cancer in terms of PSA response. As a result, in all randomized controlled trials identified for this review, isoflavones seem to have no influence on PSA levels in localized prostate cancer. The influence of isoflavones on overall survival in localized prostate cancer remains unclear. Furthermore, isoflavones are interesting substances for further research, for example in lipid metabolism and cholesterol.

Patients with degenerative cervical myelopathy have signs of blood spinal cord barrier disruption, and its magnitude correlates with myelopathy severity: a prospective comparative cohort study.

PURPOSE: The aim of this study is to detect the presence of blood spinal cord barrier (BSCB) disruption in patients with degenerative cervical myelopathy (DCM). METHODS: In this prospective non-randomized controlled cohort study, 28 patients with DCM were prospectively included. All patients had indication for neurosurgical decompression. Furthermore, 38 controls with thoracic abdominal aortic aneurysm (TAAA) and indication for surgery were included. All patients underwent neurological examination. Regarding BSCB disruption and intrathecal immunoglobulin (Ig) concentrations, cerebrospinal fluid (CSF) and blood serum were examined for albumin, IgG, IgA and IgM. Quotients (Q) (CSF/serum) were standardized and calculated according to Reibers' diagnostic criteria. RESULTS: Patients and controls distinguished significantly in their clinical status. AlbuminQ, as expression of BSCB disruption, was significantly increased in the DCM patients compared to the controls. Quotients of IgG and IgA differed significantly between the groups as an expression of intrathecal diffusion. In the subgroup analysis of patients with mild/moderate clinical status of myelopathy and patients with severe clinical status, the disruption of the BSCB was significantly increased with clinical severity. Likewise, IgAQ and IgGQ presented increased quotients related to the clinical severity of myelopathy. CONCLUSION: In this study, we detected an increased permeability and disruption of the BSCB in DCM patients. The severity of BSCB disruption and the diffusion of Ig are related to the clinical status in our patient cohort. Having documented this particular pathomechanism in patients with DCM, we suggest that this diagnostic tool cloud be an important addition to surgical decision making in the future. These slides can be retrieved under Electronic Supplementary Material.

Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA-mRNA Interaction Involvement.

Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-coding RNAs remain not fully elucidated. In the present study, we examined changes in global gene and miRNA expression and analyzed the identified miRNA-mRNA interactions after bortezomib exposure in human neuroblastoma cells to define pathways affected by this agent in this type of cells. Cell viability assays were performed to assess cytotoxicity of bortezomib. Global gene and miRNA expression profiles of neuroblastoma cells after 24-h incubation with bortezomib were determined using genome-wide RNA and miRNA microarray technology. Obtained results were then confirmed by qRT-PCR and Western blot. Further bioinformatical analysis was performed to identify affected biological processes and pathways. In total, 719 genes and 28 miRNAs were downregulated, and 319 genes and 61 miRNAs were upregulated in neuroblastoma cells treated with bortezomib. Possible interactions between dysregulated miRNA/mRNA, which could be linked to bortezomib-induced neurotoxicity, affect neurogenesis, cellular calcium transport, and neuron death. Bortezomib might exert toxic effects on neuroblastoma cells and regulate miRNA-mRNA interactions influencing vital cellular functions. Further studies on the role of specific miRNA-mRNA interactions are needed to elucidate mechanisms of bortezomib action.

Is BK Virus-Associated Cystitis a Generalized Epithelial Disease?

BK polyomavirus-associated haemorrhagic cystitis (BKHC) is a complication after allogeneic stem cell transplantation, which can occur in 5-60% of the cases. BK viruria alone can also occur in up to 100%. BKHC can lead to severe morbidity in stem cell-transplanted patients, but data about this disease is limited. Consequently, we conducted a prospective unicentric non-interventional trial on BKHC as well as BK viruria after first adult allogeneic stem cell transplantation with a follow-up time of 1 year after inpatient treatment. Between November 2013 and December 2015, we were able to include 40 adult patients with a mean age of 52.8 years. Twenty-seven (67.5%) of these patients were male and 13 (32.5%) were female. Acute myeloid leukaemia was the most frequent underlying disease (n = 15; 37.5%). Only 1 patient developed BKHC during inpatient treatment (n = 1; 2.5%), but BK viruria was frequent (n = 11; 27.5%) during inpatient treatment as well as in the follow-up time (n = 14; 35%). Interestingly, BK viruria was significantly associated with mucositis (p = 0.038) and number of transfused platelet concentrates (p = 0.001). This unexpected association will be discussed and needs further investigation.

Comparison of intravenous or intravesical cidofovir in the treatment of BK polyomavirus-associated hemorrhagic cystitis following adult allogeneic stem cell transplantation-A systematic review.

INTRODUCTION: BK polyomavirus can lead to hemorrhagic cystitis (BKPyV-HC) in allogeneic stem cell transplantation and therefore to increased morbidity. No causal therapy has been established yet. Cidofovir (CDV) is a nucleotide analog of cytosine that is active against various DNA viruses and it has been described for therapy of BKPyV-HC using 2 admission routes: intravenous and intravesical. METHODS: We performed a systematic review regarding the comparison of intravenous or intravesical cidofovir in the treatment of BKPyV-HC following adult allogeneic stem cell transplantation. Since there is a lack of randomized controlled trials, we considered all kinds of studies for this review. Due to heterogeneity of the data, we were not able to perform a meta-analysis, so the results are shown descriptively. RESULTS: The literature search for primary studies yielded 232 results. Finally, 9 studies where considered which included a total of 189 adult patients with BKPyV-HC after allogeneic stem cell transplantation. We could only identify retrospective studies for this review. A total of 172 patients received intravenous CDV, 17 patients received intravesical CDV, and 2 patients received CDV in both admission routes. In 68.0% of the cases, a complete response for intravenous CDV was documented and in 88.2% for intravesical CDV. Interestingly, no kidney toxicity was mentioned in intravesical CDV. 9.3% of the intravenously treated patients had renal failure. CONCLUSION: There is only weak evidence for the use of CDV. The intravesical admission route should be further investigated because of a good toxicity profile.

The combination of mitomycin-induced blood cells with a temporary treatment of ciclosporin A prolongs allograft survival in vascularized composite allotransplantation.

BACKGROUND: Vascularized composite allotransplantation (VCA) is a rapidly expanding field of transplantation and provides a potential treatment for complex tissue defects. Peripheral blood mononuclear cells (PBMCs) shortly incubated with the antibiotic and chemotherapeutic agent mitomycin C (MMC) can suppress allogeneic T cell response and control allograft rejection in various organ transplantation models. MMC-incubated PBMCs (MICs) are currently being tested in a phase I clinical trial in kidney transplant patients. Previous studies with MICs in a complex VCA model showed the immunomodulatory potential of these cells. The aim of this study is to optimize and evaluate the use of MICs in combination with a standard immunosuppressive drug in VCA. METHODS: Fully mismatched rats were used as hind limb donors [Lewis (RT11)] and recipients [Brown-Norway (RT1n)]. Sixty allogeneic hind limb transplantations were performed in six groups. Group A received donor-derived MICs combined with a temporary ciclosporin A (CsA) treatment. Group B received MICs in combination with a temporarily administered reduced dose of CsA. Group C served as a control and received a standard CsA dose temporarily without an additional administration of MICs, whereas Group D was solely medicated with a reduced CsA dose. Group E received no immunosuppressive therapy, neither CsA nor MICs. Group F was given a continuous standard immunosuppressive regimen consisting of CsA and prednisolone. The endpoint of the study was the onset of allograft rejection which was assessed clinically and histologically. RESULTS: In group A and B, the rejection-free interval of the allograft was significantly prolonged to an average of 23.1 ± 1.7 and 24.7 ± 1.8 days compared to the corresponding control groups (p < 0.01). Rejection in groups C, D, and E was noted after 14.3 ± 1.1, 7.8 ± 0.7, and 6.9 ± 0.6 days. No rejection occurred in control group F during the follow-up period of 100 days. No adverse events have been noted. CONCLUSION: The findings of this study show that the combination of MICs with a temporary CsA treatment significantly prolongs the rejection-free interval in a complex VCA model. The combination of MICs with CsA showed no adverse events such as graft-versus-host disease. MICs, which are generated by a simple and reliable in vitro technique, represent a potential therapeutic tool for prolonging allograft survival through immunomodulation.

Assessing the severity of acute pancreatitis (ASAP) in Switzerland: A nationwide survey on severity assessment in daily clinical practice.

BACKGROUND/OBJECTIVES: We aim to assess which tools for severity stratification in acute pancreatitis are used in today's daily clinical practice and to what extent the new Atlanta classification is being implemented by the medical community in Switzerland. METHODS: The heads of surgical, medical and emergency departments of Swiss hospitals (n = 83) that directly treat patients with acute pancreatitis were given access to an online survey and asked to forward the questionnaire to their team. The questionnaire consisted of 16 items, including questions about the specialty background of the participants, the allocation of patients with AP, severity assessment, patient management, the role of imaging procedures, and future perspectives. RESULTS: A total of 233 participants from 63 hospitals responded (response rate, 74%). A vast majority of participants [198 (87%)] does assess severity. The most frequently used tools are the Ranson [108 (87%)] and APACHE II scores [28 (23%)]. A majority of the participants were not satisfied with the currently available tools to assess severity [130 (59%)]. A minority [15 (12%)] use the revised Atlanta classification to assess the degree of severity in AP. CONCLUSIONS: The Ranson score remains the dominant risk stratification tool in clinical practice in Switzerland, followed by the APACHE II score. Other modern instruments, such as the Atlanta 2012 classification, have not yet earned broad recognition and have not reached daily practice. Further efforts must be made to expand physicians' awareness of their existence and significance.

Are the Polyomaviruses BK and JC Associated with Opportunistic Infections, Graft-versus-Host Disease, or Worse Outcomes in Adult Patients Receiving Their First Allogeneic Stem Cell Transplantation with Low-Dose Alemtuzumab?

BACKGROUND: The association of polyomaviruses BK and JC with other opportunistic infections and graft-versus-host disease (GvHD) in allogeneic stem cell transplantation is controversially discussed. METHODS: We conducted a retrospective study of 64 adult patients who received their first allogeneic stem cell transplantation between March 2010 and December 2014; the follow-up time was 2 years. RESULTS: Acute leukemia was the most frequent underlying disease (45.3%), and conditioning included myeloablative (67.2%) and nonmyeloablative protocols (32.8%). All patients received 10 mg of alemtuzumab on day -2 (20 mg in case of mismatch) as GvHD prophylaxis. Twenty-seven patients (41.5%) developed cytomegalovirus (CMV) reactivation. BKPyV-associated hemorrhagic cystitis was diagnosed in 10 patients (15.6%). Other opportunistic infections caused by viruses or protozoa occurred rarely (<10%). There was no association of BKPyV or JCPyV with CMV reactivation, Epstein-Barr virus reactivation, human herpes virus 6, or parvovirus B19 infection requiring treatment. There was a significant correlation of BKPyV-associated hemorrhagic cystitis with toxoplasmosis (p = 0.013). Additionally, there was a significant link of simultaneous BKPyV and JCPyV viruria with toxoplasmosis (p = 0.047). BKPyV and JCPyV were not associated with GvHD, relapse, or death. CONCLUSION: We found no association of BKPyV or JCPyV with viral infections or GvHD. Only the correlation of both polyomaviruses with toxoplasmosis was significant. This is a novel and interesting finding.

Development of a short scale for assessing economic environmental aspects in patients with spinal diseases using Rasch analysis.

BACKGROUND: Economic environmental factors represent important barriers to participation and have deleterious effects on quality of life (QOL) in persons with spinal diseases (SpD). While economic factors are anchored in the International Classification of Functioning, Disability and Health, their influence on QOL and participation from patients' perspectives is an infrequent focus of research. The aim of the present research is to calibrate a culturally adapted Rasch-based questionnaire assessing economic QOL in patients with SpD. METHODS: The 11-items of the German economic-QOL-scale were answered by 325 patients with SpD on a four-point Likert-scale. Fit to the Rasch measurement model was investigated by testing for stochastic ordering of the items, unidimensionality, local independence, and differential item functioning (DIF). RESULTS: After adjusting for local dependency, fit to the Rasch model was achieved with a non-significant item-trait interaction (chi-squaredf = 20 = 34.8, p = 0.021). The person separation reliability equaled 0.88, the scale was free from age- or gender-related DIF, and unidimensionality could be verified. CONCLUSIONS: The Rasch-based German version of the economic-QOL-scale represents a suitable instrument to investigate the influences of economic factors on patients' QOL at a group and individual level. It can be easily applied in research and practice and may be administered quickly in combination with other instruments. The short test duration implies a low test burden for patients and a minimum of time expenditure by clinicians when evaluating the results.

Local administration of Mitomycin-C-Treated peripheral blood mononuclear cells (PBMCs) prolongs allograft survival in vascularized composite allotransplantation.

BACKGROUND: VCA offers a potential treatment for extensive tissue defects. First results of systemic administration of Mitomycin C-treated PBMCs in VCA demonstrated a significant prolongation of allograft survival. The aim of this study is to evaluate if local administration of MMC-PBMCs prolongs allograft survival in allogeneic hind limb transplantations of the rat. METHODS: Sixty allogeneic hind limb transplantations in the rat were performed in six groups. Lewis rats (LEW) were used as hind limb donors and Brown-Norway rats (BN) as recipients. Animals in group A received donor-derived MMC-treated PBMCs locally (i.m.). Group B received no immunosuppressive therapy, group C received a standard immunosuppressive regime consisting of FK506 and Prednisolon, group D (BN to BN) comprised isograft transplantations without immunosuppressive treatment, group E received non-treated PBMCs (i.m.) and group F received phosphate buffered saline (PBS) without cells. The transplanted hind limbs were assessed for color, edema, skin, hair condition, and consistency of the thigh every 8 hours. RESULTS: Rejection in group A was delayed to an average of 7.2 ± 0.6 days. Survival times were significantly prolonged (P < 0.01) compared to control groups B, E, and F (5.5 ± 0.7, 5.8 ± 0.7, and 5.7 ± 0.5 days). Control groups C and D showed no signs of rejection. CONCLUSION: The findings of this study show that local administration of MMC-PBMCs has no side effects and significantly extends allograft survival. Further experiments with MMC-PBMCs treatments repeated at different time-points and being added to low dose immunosuppressive protocols need to be performed to improve experimental and eventually clinical outcome after VCA. © 2015 Wiley Periodicals, Inc. Microsurgery 36:417-425, 2016.

Laboratory markers predicting severity of acute pancreatitis.

Acute pancreatitis (AP) is an inflammatory disease of highly variable severity, ranging from mild cases with low mortality to severe cases with high mortality. Numerous biomarkers have been studied as potential early predictors of the severity of this disease so that treatment can be optimally tailored to prevent complications. We aim to present and discuss the most relevant biomarkers for early severity assessment in AP that have been studied to date. We review the current literature on biomarkers that have been used to predict the severity in AP. C-reactive protein (CRP) is still considered to be the gold standard, with a cut-off value of 150 mg/ml 48 h after disease onset. Other markers, including procalcitonin (PCT) and interleukin 6 (IL-6) have been implemented in some hospitals, but are not used on a routine basis. Most other markers, including acute phase proteins (LBP, SAA, PTX3), cytokines (Il-8, TNF-a, MIF), activation peptides of pancreatic proteases (TAP, CAPAP, PLAP), antiproteases (AAT, a2M), adhesion molecules (ICAM-1, selectins, E-cadherin) and leukocyte-derived enzymes (PA2, PMN-E) have shown some promising results but have not been routinely implemented. Furthermore, new and interesting biomarkers (Copeptin, TRX-1, Ang-2, E-2) have shown good results, but more research is needed to determine if they could play a role in the future. Various reasons why new markers for disease severity have not been adopted in daily routine include low accuracy, cumbersome laboratory techniques and high cost. Despite these difficulties, research is still very active in finding new markers to predict the severity of AP.

Proper synaptic vesicle formation and neuronal network activity critically rely on syndapin I.

Synaptic transmission relies on effective and accurate compensatory endocytosis. F-BAR proteins may serve as membrane curvature sensors and/or inducers and thereby support membrane remodelling processes; yet, their in vivo functions urgently await disclosure. We demonstrate that the F-BAR protein syndapin I is crucial for proper brain function. Syndapin I knockout (KO) mice suffer from seizures, a phenotype consistent with excessive hippocampal network activity. Loss of syndapin I causes defects in presynaptic membrane trafficking processes, which are especially evident under high-capacity retrieval conditions, accumulation of endocytic intermediates, loss of synaptic vesicle (SV) size control, impaired activity-dependent SV retrieval and defective synaptic activity. Detailed molecular analyses demonstrate that syndapin I plays an important role in the recruitment of all dynamin isoforms, central players in vesicle fission reactions, to the membrane. Consistently, syndapin I KO mice share phenotypes with dynamin I KO mice, whereas their seizure phenotype is very reminiscent of fitful mice expressing a mutant dynamin. Thus, syndapin I acts as pivotal membrane anchoring factor for dynamins during regeneration of SVs.