Confluent abscesses in autochthonous back muscles after spinal injections

Wiener Medizinische Wochenschrift - Injection therapy is a frequently used method for the treatment of subacute and chronic low back pain (LBP) despite scant evidence for its...     

Eurotransplant donor‐risk‐index and recipient factors: influence on long‐term outcome after liver transplantation – A large single‐center experience

The organ shortage has led to increased use of marginal organs. The Eurotransplant Donor‐Risk‐Index (ET‐DRI) was established to estimate outcome after Liver Transplantation (LT). Currently, data on impact of ET‐DRI on long‐term outcome for different indications and recipient conditions are missing. Retrospective, single‐center analysis of long‐term graft survival (GS) of 1767 adult primary LTs according to indication, labMELDcategory (1: ≤18; 2: >18–25; 3: >25–35; 4: >35), and ET‐DRI. Mean ET‐DRI in our cohort was 1.63 (±0.43). One‐, 10, and 15‐yr GS was 83.5%, 63.3%, and 54.8%. Long‐term GS was significantly influenced by ET‐DRI. Accordingly, four ET‐DRI categories were defined and analyzed with respect to underlying disease. Significant impact of these categories was observed for: Alcohol, cholestatic/autoimmune diseases (CD/AIH), and HCV, but not for HCC, HBV, cryptogenic cirrhosis, and acute liver failure. labMELD categories showed no significant influence on graft, but on patient survival. Matching ET‐DRI categories with labMELD revealed significant differences in long‐term GS for labMELDcategories 1, 2, and 3, but not 4. In multivariate analysis, HCV combined with ET‐DRI > 2 and labMELDcategory 3 combined with ET‐DRI > 2 emerged as negative predictors. To achieve excellent long‐term graft survival, higher risk organs (ET‐DRI > 1.4) should be used restrictively for patients with CD/AIH or HCV. Organs with ET‐DRI > 2 should be avoided in patients with a labMELD of >25–35.     

Influence of antithymocyte globulin treatment of brain‐dead organ donor on inflammatory response in cardiac grafts: an experimental study in mice

The expression of proinflammatory cytokines in donor hearts after antithymocyte globulin (ATG) treatment given prior to organ removal was evaluated to analyze changes in inflammatory response. Adult female OF‐1 mice were randomized into brain death (BD) groups (BD Control, BD ATG) with or without treatment, and Controls (Control, ATG). BD induction was performed through gradual inflation of an intracranial positioned balloon catheter. At the end of a 6‐h observation period, ATG (1 mg/kg BW) was given intravenously. After 45 min, the donor hearts were removed. Proinflammatory markers IL‐2 and IL‐6 were examined using ELISA and immunohistochemistry staining. After single administration of ATG, the inflammatory reaction in the myocardium showed a significant reduction in IL‐2 expression (BD Control vs. BD ATG, P = 0.033). Our investigation showed expected increase in proinflammatory mediators after BD. This increase was abolished by single infusion of ATG, indicated by significant reduction in IL‐2 levels in the myocardium. We observed a reduction of IL‐6 deposition in media cells in ATG‐treated specimens. Further research is necessary to evaluate the role of ATG in donor management considering a potentially positive effect of ATG on IL‐2‐directed inflammatory response and possible reduction of IL‐6‐mediated vascular changes.     

DAA‐based antiviral treatment of patients with chronic hepatitis C in the pre‐ and postkidney transplantation setting

DAA‐based regimens for chronic hepatitis C infection encourage treatment of “difficult‐to‐treat” cohorts. This study investigated efficacy and safety of DAA‐based regimens in HCV patients on dialysis or postkidney or liver/kidney transplantation. Twenty‐five patients treated with DAA combinations were evaluated: 10 were on dialysis (eight: hemodialysis, two: peritoneal dialysis), eight were kidney transplant recipients, and seven were liver/kidney transplant recipients. Except for one patient treated with daclatasvir ([DCV]/60 mg/QD)/simeprevir ([SMV]/150 mg/QD), the others received sofosbuvir‐based regimens ([SOF];400 mg/QD) combined with SMV:eight, DCV:13 or either ledipasvir ([LDV]90 mg/QD), ribavirin ([RBV];weight based) or pegylated interferon/RBV. HCV‐RNA was determined by Abbott RealTime (LLOQ]:12 IU/ml) or Roche AmpliPrep/COBAS TaqMan assay (LLOQ:15 IU/ml); treatment response evaluated every 4 weeks, at the end of treatment, and 4 and 12 weeks thereafter. Twenty‐four (96%) patients achieved SVR 12/24 (ITT‐analysis). Mean treatment duration was 15.1 ± 5.1 weeks (±SD), and two patients terminated prematurely – both reached SVR12. Six patients were hospitalized due to complications of underlying disease. One patient achieved SVR24 but was re‐infected (week 27). Kidney function remained stable; serum creatinine increased in only one patient – SOF was reduced to 400 mg/48 h. Treatment with DAA combinations in renally impaired HCV patients is highly effective and well tolerated. These findings call for further controlled trials and data from real‐life cohorts.     

Eph/ephrin signaling in the kidney and lower urinary tract

Development and homeostasis of the highly specialized cell types and tissues that constitute the organs of the urinary system, the kidneys and ureters, the bladder, and the urethra, require the tightly regulated exchange of signals in and between these tissues. Eph/ephrin signaling is a bidirectional signaling pathway that has been functionally implicated in many developmental and homeostatic contexts, most prominently in the vascular and neural system. Expression and knockout analyses have now provided evidence that Eph/ephrin signaling is of crucial relevance for cell and tissue interactions in the urinary system as well. A clear requirement has emerged in the formation of the vesicoureteric junction, in urorectal septation and glomerulogenesis during embryonic development, in maintenance of medullary tubular cells and podocytes in homeostasis, and in podocyte and glomerular injury responses. Deregulation of Eph/ephrin signaling may also contribute to the formation and progression of tumors in the urinary system, most prominently bladder and renal cell carcinoma. While in the embryonic contexts Eph/ephrin signaling regulates adhesion of epithelial cells, in the adult setting, cell-shape changes and cell survival seem to be the primary cellular processes mediated by this signaling module. With progression of the genetic analyses of mice conditionally mutant for compound alleles of Eph receptor and ephrin ligand genes, additional essential functions are likely to arise in the urinary system.     

Multifocal Versus Solitary Papillary Thyroid Carcinoma

Background

Papillary Thyroid Carcinoma (PTC) which accounts for >85 % of all thyroid cancers in iodine-rich areas, appears either as a single tumor or as two or more, neoplastic foci within the thyroid gland (Multifocal PTC). We present the comparative results between solitary and MFC PTC.

Materials and methods

Demographics, tumor characteristics (size, laterality, foci number, histologic subtype) and TNM staging were compared between solitary and MFPTC patients. The presence of lymphocytic or Hashimoto’s thyroditis was also recorded.

Results

From January 2008 to December 2012, among 647 PTC patients, 241(37.2 %) had MFPTC 177 females (73.4 %) and 64 males (26.6 %), mean age 48.5 years (range 12–87). Mean number of tumor foci was 3.3 (range 2–26). MFPTC patients presented with more advanced T stage (28.2 vs. 18.7 %, p = 0.01) and more LN metastases (28.6 vs. 15.5 %, p < 0.001). Foci number correlates with male gender and LN metastases (p = 0.014 and p = 0.019, respectively). Central (N1a) or lateral (N1b) LN involvement correlates strongly with male gender (p  = 0.024) and younger age (p < 0.001). The follicular variant was the next most frequent histologic subtype associated with extremely rare LN metastases.

Conclusion

MFPTC comprises a more aggressive form of papillary thyroid cancer since it is associated with more frequent N1a/ N1b disease and occurs more frequently in T3/T4 patients. MFPTC foci number correlates with male gender and LN metastases.

     

Chondrocyte cultures from human proximal interphalangeal finger joints

Osteoarthritis (OA) of the hand is a common disease resulting in pain and impaired function. The pathogenesis of hand OA (HOA) is elusive and models to study it have not been described. Chondrocyte culture has been essential to understand cartilage degeneration, which is a hallmark of OA. We investigated the feasibility of human chondrocyte culture derived from proximal interphalangeal (PIP) finger joints. Hyaline cartilage of the PIP and knee joints was obtained from human cadavers. Chondrocytes harvested up to 236 h after death of the donors were viable and expressed chondrocyte‐specific genes. Gene expression comparing chondrocytes from PIP and knee joints using Affymetrix GeneChip arrays resulted in a unique PIP‐specific gene expression pattern. Genes involved in developmental processes including the WNT pathway were differentially expressed between the joints. These findings suggest that our knowledge on chondrocyte biology derived mainly from knee and hip joints may not apply to chondrocytes of the PIP joints and some of the distinctive features of HOA may be caused by the specific properties of PIP chondrocytes. Chondrocyte culture of PIP cartilage is a novel tool to study cartilage degeneration in HOA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1569–1575, 2016.     

Synthesis and preclinical evaluation of an Al<Superscript>18</Superscript>F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand

Purpose

The aim of this study was to synthesize and preclinically evaluate an ¹⁸F-PSMA positron emission tomography (PET) tracer. Prostate-specific membrane antigen (PSMA) specificity, biodistribution, and dosimetry in healthy and tumor-bearing mice were determined.

Methods

Several conditions for the labeling of ¹⁸F-PSMA-11 via ¹⁸F-AlF-complexation were screened to study the influence of reaction temperature, peptide amount, ethanol volume, and reaction time. After synthesis optimization, biodistribution and dosimetry studies were performed in C57BL6 mice. For proof of PSMA-specificity, mice were implanted with PSMA-negative (PC3) and PSMA-positive (LNCaP) tumors in contralateral flanks. Static and dynamic microPET/computed tomography (CT) imaging was performed.

Results

Quantitative labeling yields could be achieved with >97 % radiochemical purity. The ¹⁸F-PSMA-11 uptake was more than 24-fold higher in PSMA-high LNCaP than in PSMA-low PC3 tumors (18.4?±?3.3 %ID/g and 0.795?±?0.260 %ID/g, respectively; p?<?4.2e-5). Results were confirmed by ex vivo gamma counter analysis of tissues after the last imaging time point. The highest absorbed dose was reported for the kidneys. The maximum effective dose for an administered activity of 200 MBq was 1.72 mSv.

Conclusion

¹⁸F-PSMA-11 using direct labeling of chelate-attached peptide with aluminum-fluoride detected PSMA-expressing tumors with high tumor-to-liver ratios. The kidneys were the dose-limiting organs. Even by applying the most stringent dosimetric calculations, injected activities of up to 0.56 GBq are feasible.