Orbital floor reconstruction with resorbable polydioxanone implants

Many different materials are proposed for reconstruction of traumatic orbital floor defects. Donor-site morbidity of autologous transplants and infections or extrusions of nonresorbable implants lead to a widespread use of resorbable, alloplastic materials such as polydioxanone (PDS). The goal of this study was to evaluate the prevalence of orbital floor fracture-related problems after surgical treatment using PDS. Ophthalmologic and clinical examinations were performed at 194 patients before orbital floor reconstruction, 14 days and 6 months after surgery (approximate defect sizes: <1 cm2, n=50; 1-2 cm2, n=97; >2 cm2, n=47). Clinical findings including the ocular motility, the sensibility of the infraorbital nerve, and the position of the globe were evaluated. For statistical analysis of categorical data, confidence intervals of percentages were determined. Linear relationships between 2 variables were assessed with Pearson correlation analysis. A reduced ocular motility was diagnosed in 60 patients (31%) before surgery; in 14 patients (7%), 2 weeks; and in 10 patients (5%), 6 months after surgery. Infraorbital hypesthesia was found in 120 patients (62%) before surgery; in 47 patients (24%), 2 weeks; and in 35 patients (18%), 6 months after surgery. An enophthalmos was present in 10 patients (5%) before surgery, and in 4 patients (2%), 6 months after surgery. Our data suggest that PDS is a suitable implant for orbital floor reconstruction with acceptable low rates of infraorbital hypesthesia, bulbus motility disturbances, and enophthalmos. Polydioxanone can also be used for orbital floor defects exceeding 2 cm2.     

A pilot study investigating the effects of remote ischemic preconditioning in high-risk cardiac surgery using a randomised controlled double-blind protocol

The efficacy of remote ischemic preconditioning (RIPC) in high-risk cardiac surgery is uncertain. In this study, 96 adults undergoing high-risk cardiac surgery were randomised to RIPC (3 cycles of 5 min of upper-limb ischemia induced by inflating a blood pressure cuff to 200 mmHg with 5 min of reperfusion) or control. Main endpoints were plasma high-sensitivity troponin T (hsTNT) levels at 6 and 12 h, worst post-operative acute kidney injury (AKI) based on RIFLE criteria, and noradrenaline duration. hsTNT levels were log-normally distributed and higher with RIPC than control at 6-h post cross-clamp removal [810 ng/ml (IQR 527-1,724) vs. 634 ng/ml (429-1,012); ratio of means 1.41 (99.17% CI 0.92-2.17); P=0.04] and 12 h [742 ng/ml (IQR 427-1,700) vs. 514 ng/ml (IQR 356-833); ratio of means 1.56 (99.17% CI 0.97-2.53); P=0.01]. After adjustment for baseline confounders, the ratio of means of hsTNT at 6 h was 1.23 (99.17% CI 0.88-1.72; P=0.10) and at 12 h was 1.30 (99.17% CI 0.92-1.84; P=0.05). In the RIPC group, 35/48 (72.9%) had no AKI, 5/48 (10.4%) had AKI risk, and 8/48 (16.7%) had either renal injury or failure compared to the control group where 34/48 (70.8%) had no AKI, 7/48 (14.6%) had AKI risk, and 7/48 (14.6%) had renal injury or failure (Chi-squared 0.41; two degrees of freedom; P = 0.82). RIPC increased post-operative duration of noradrenaline support [21 h (IQR 7-45) vs. 9 h (IQR 3-19); ratio of means 1.70 (99.17% CI 0.86-3.34); P=0.04]. RIPC does not reduce hsTNT, AKI, or ICU-support requirements in high-risk cardiac surgery.     

On the symmetry of siblings: automated single-cell tracking to quantify the behavior of hematopoietic stem cells in a biomimetic setup

The interplay between hematopoietic stem and progenitor cells (HSPC) and their local microenvironment is a key mechanism for the organization of hematopoiesis. To quantitatively study this process, a time-resolved analysis of cellular dynamics at the single-cell level is an essential prerequisite. One way to generate sufficient amounts of appropriate data is automatic single-cell tracking using time-lapse video microscopy. We describe and apply newly developed computational algorithms that allow for an automated generation of high-content data of single-cell characteristics at high temporal and spatial resolution, together with the reconstruction and statistical evaluation of complete genealogical histories. This methodology has been applied to the particular example of purified primary human HSPCs in bioengineered culture conditions. The combination of genealogical information and dynamic profiles of cellular properties identified a marked symmetry between sibling HSPCs regarding cell cycle time, but also migration speed and growth kinetics. Furthermore, we demonstrate that this symmetry of HSPC siblings can be altered by exogenous cues of the local biomimetic microenvironment. Using the example of HSPC growth in biomimetic culture systems, we show that our approach provides a valuable tool for the quantitative analysis of dynamic single-cell features under defined in?vitro conditions, allowing for integration of functional and genealogical data. The efficiency and accuracy of our approach pave the way for new and intriguing insights into the organizational principles of developmental patterns and the respective influence of exogenous cues not limited to the study of primary HSPCs.     

Treatment with Thalidomide and Cyclophosphamide (TCID) is Superior to Vincristine (VID) and to Vinorelbine (VRID) Regimens in Patients with Refractory or Recurrent Multiple Myeloma

Treatment of relapsed or refractory multiple myeloma remains a challenge and novel treatment regimen are required. Here, a matched pair analysis was performed comparing TCID (thalidomide, cyclophosphamide, idarubicin, dexamethasone) treatment to the treatment of patients with VID (vincristine, idarubicin, dexamethasone) or with VRID (vinorelbine, idarubicin, dexamethasone) for relapsed or refractory multiple myeloma. In total, 197 patients were enrolled in multicenter trials. After matching for important prognostic variables 46 matched-pairs (total of 138 patients) could be analysed with regard to survival, toxicity and efficacy. Interestingly, a significant improvement of overall response rate (ORR) for TCID treatment compared to VID and VRID was found. In addition, TCID treatment also led to a significantly higher overall survival (OS) as well as progression-free survival (PFS) compared to VID and VRID. In conclusion, TCID treatment appears to be superior to VRID and VID treatment in patients with progressive or refractory myeloma.     

Severe case and literature review of primary erythromelalgia: novel SCN9A gene mutation

Erythromelalgia is a rare clinical syndrome characterized by intermittent heat, redness, swelling and pain more commonly affecting the lower extremities. Symptoms are mostly aggravated by warmth and are eased by a cold temperature. In some cases, symptoms can be very severe and disabling. Erythromelalgia can be classified as either familial or sporadic, with the familial form inherited in an autosomal dominant manner. Recently, there has been a lot of progress in studying Na(v)1.7 sodium channels (expressed mostly in the sympathetic and nociceptive small-diameter sensory neurons of the dorsal root ganglion) and different mutations affecting the encoding SCN9A gene that leads to channelopathies responsible for some disorders, including primary erythromelalgia. We present a severe case of progressive primary erythromelalgia caused by a new de novo heterozygous missense mutation (c.2623C>G) of the SCN9A gene which substitutes glutamine 875 by glutamic acid (p.Q875E). To our knowledge, this mutation has not been previously reported in the literature. We also provided a short literature review about erythromelalgia and Na(v) sodium channelopathies.     

Wire fractures in Solysafe septal occluders: a single center experience

Objectives : To determine the incidence of device fractures (DF) after implantation of a Solysafe® Septal Occluder (iSSO) and to assess the spectrum of associated problems. Background : In August 2010, after initial unpublished reports on DF, the manufacturer issued an “urgent field safety notice,” prompting all medical care providers to re‐examine all patients after iSSO. Methods : Prospective single center study. Extended follow‐up examination, including standardized fluoroscopy (sF), was performed in all patients after iSSO. Results : A total of 111 patients had undergone iSSO at our institution between June 2005 and July 2010. Median age and body weight were 50 years (9.3–79.6) and 75 kg (29–122), respectively. Indications for iSSO were (1) patent foramen ovale in patients with a history of cryptogenic stroke (n = 84; 76%) and (2) hemodynamically significant atrial septal defect of the secundum type (n = 27; 24%). A total of 113 devices were implanted. Complete follow‐up was available in 103 patients (92.8%). Median follow‐up was 1.9 years (0–5.2). There were no postimplantation neurological events or symptoms. The closure rate was 97.1%. DF was suspected on a chest X‐ray in one patient and documented in 10 patients by sF. The overall probability of freedom from DF was 82.3% after 5 years. One patient had embolization of a device fragment to the right pulmonary artery. So far, all patients with DF have been managed conservatively. Conclusions : The incidence of DF after iSSO is unacceptably high. sF is imperative for accurate diagnosis of DF. Further, follow‐up is needed to determine the risk of clinical complications and to optimize management. © 2012 Wiley Periodicals, Inc.     

Making a Difference: Monocyte Heterogeneity in Cardiovascular Disease

Monocytes are frequently described as bone marrow-derived precursors of macrophages. Although many studies support this view, we now appreciate that monocytes neither develop exclusively in the bone marrow nor give rise to all macrophages and dendritic cells. In addition to differentiating to specific leukocyte populations, monocytes, as monocytes, are functionally and ontogenically heterogeneous. In this review we will focus on the development and activity of monocytes and their subsets in mice (Ly-6?C(high/low)) and humans (CD14(+/dim/-) CD16(+/-)) in the context of atherosclerosis and its complications.     

Enzyme immobilization inside the porous wood structure: a natural scaffold for continuous-flow biocatalysis

Enzymes are often immobilized on solid supports to enable their recovery from reaction solutions, facilitate their reuse and hence increase cost-effectiveness in their application. Immobilized enzymes may even be used for flow-through applications in continuous processes. However, the synthesis of traditional immobilization scaffolds and immobilization techniques lack sustainability as they are often based on fuel-based materials and tedious synthesis- and immobilization approaches. Here, we present the natural material wood as a green alternative for enzyme immobilization. Its natural structure provides a mechanically stable porous scaffold with a high inner surface area that allows for directional flow-through of liquids. Enzymes were immobilized by nanoparticle-mediated adsorption, a simple, versatile and completely water-based process. The resulting wood–enzyme hybrids were intensely investigated for the model enzyme laccase. Reaction kinetics, as well as catalytic activities at various pH-values, temperatures, and ionic strengths were determined. The wood–enzyme hybrids could quickly and completely be removed from the reaction solution. Hence, they allow for multifold reusability. We show a series of 25 consecutive reaction cycles with a remaining activity in the last cycle of 90% of the maximal activity. Moreover, the anisotropic porosity of wood enabled the application of the hybrid material as a biocatalytic flow-through reactor. Flow-rate dependent productivity of a single-enzyme reaction was determined. Moreover, we show a two-step reaction cascade in continuous flow by the immobilization of the enzymes glucose oxidase and horseradish peroxidase. Therefore, the natural material wood proved to be a promising material for application in continuous-flow biocatalysis.

Green biocatalytic systems for continuous-flow cascade reactions are realized by enzyme immobilization inside the porous wood structure.