The extended endoscopic approach to perisellar and skull base lesions: is one nostril enough?

Neurosurgical Review - The extended endonasal endoscopic approach to the skull base is still under investigation. The main advantage of using this technique is to approach lesions in a minimally...     

Impact of left ventricular assist device therapy on the cardiac proteome and metabolome composition in ischemic cardiomyopathy

The changes in the myocardial proteome and metabolome associated with left ventricular assist device (LVAD) therapy in patients with ischemic cardiomyopathy (ICM) are poorly characterized. We investigated the impact of mechanical unloading following LVAD therapy on the myocardial proteome and metabolome. Matched samples of 5 patients’ myocardial tissue, harvested at the time of LVAD implant (“pre-LVAD”) or heart transplant (“post-LVAD”), were studied by quantitative proteomics and metabolomics as well as being probed for T-tubule structure and connexin-43 distribution. Moreover, pre-LVAD proteome profiles of ICM context were bioinformatically compared to pre-LVAD proteome profiles of dilated cardiac myopathy (DCM). More than 2120 proteins were reliably identified and quantified in paired patient samples. LVAD therapy led to proteomic remodeling, including reduced levels of α-1-antichymotrypsin together with an overall decrease of immune response proteins and an increase of proteins involved in membrane biology. Metabolomics highlighted increased glucose and glucose-6-phosphate levels in the left ventricle upon LVAD therapy. Wheat germ agglutinin staining demonstrated improved T-tubule structure. Connexin-43 displayed a trend for more pronounced intercalated disc localization. In comparing pre-LVAD proteome profiles of ICM context with pre-LVAD proteome profiles of dilated cardiac myopathy (DCM), we noticed an overrepresentation in ICM of proteins associated with humoral immune response. Our findings underline an impact of LVAD therapy on left ventricular biology in ICM. The proteomic, metabolomic, and structural alterations described here are typically associated with cardiac recovery. On the molecular level, our findings indicate the possibility of cardiac remodeling under LVAD therapy in ICM.     

The Uruguayan semen donor population: A twenty-eight-year retrospective study

Several studies have reported a global decline in seminal quality over the years. The objective of this study was to describe the semen donor population of Uruguay through comparing data of successive samples banked by the same donors and the analysis of their semen and physical characteristics, ancestry origin and educational level. A total of 3,449 ejaculated samples collected from 71 donors, cryobanked between 1989 and March 2017 at Fertilab, were analysed. Results revealed a mean age of 23.90 ± 3.98 years, an average weight of 74.95 ± 1.09 kg and a mean height of 1.78 ± 0.06 m. The majority of the donors trace their origin to Europe (74.65%, 53/71) and 66.19% (47/71) have a level of education higher than secondary school. We observed longitudinal differences in two parameters, that is sperm concentration and semen volume. Sperm concentration declined, while semen volume increased significantly over the 28-year period. The results of the present study are in accordance with that of previous articles that also reported a decline in sperm concentration over time. However, no differences were observed in total sperm number per ejaculate due to the increase in semen volume values, thus reflecting no real changes in sperm production over time.     

Incisional negative pressure wound therapy does not reduce surgical site infections in abdominal midline incisions: a case control study

Abstract

Purpose: There is evidence from various surgical specialties that incisional negative pressure wound therapy (iNPWT) might reduce postoperative surgical site infections (SSIs). In visceral and general surgery, there is varying evidence of its efficacy in reducing surgical site infections.

Methods: A prospectively registered patient cohort of 43 patients with abdominal wall and visceral surgery received treatment with iNPWT and was compared to a matched retrospective cohort to analyze its effects on SSI occurrence and respective risk factors. Groups were matched by procedure, sex, body mass index and age. We used two different systems of iNPWT: (i) PREVENA^TM or (ii) self-made epicutaneous iNPWT from common VAC material.

Results: We could not find a total reduction in postoperative SSIs by application of iNPWT. But within the iNPWT cohort, patients with self-made iNPWT suffered more often from SSIs compared to the commercial iNPWT subgroup. No patient specific risk factors could be identified to advocate the use of iNPWT.

Conclusion: Our data do not support the use of an incisional negative pressure wound therapy on closed wounds in midline laparotomy incisions. Although, differences exist between the commmercial and self-made systems.     

How to Regulate Nonbiological Complex Drugs (NBCD) and Their Follow-on Versions: Points to Consider

The aim of this critical review is to reach a global consensus regarding the introduction of follow-on versions of nonbiological complex drugs (NBCD). A nonbiological complex drug is a medicinal product, not being a biological medicine, where the active substance is not a homo-molecular structure, but consists of different (closely related and often nanoparticulate) structures that cannot be isolated and fully quantitated, characterized and/or described by state of the art physicochemical analytical means and where the clinical meaning of the differences is not known. The composition, quality and in vivo performance of NBCD are highly dependent on manufacturing processes of both the active ingredient as well as in most cases the formulation. The challenges posed by the development of follow-on versions of NBCD are illustrated in this paper by discussing the ‘families’ of liposomes, iron–carbohydrate (‘iron–sugar’) drugs and glatiramoids. It is proposed that the same principles for the marketing authorization of copies of NBCD as for biosimilars be used: the need for animal and/or clinical data and the need to show similarity in quality, safety and efficacy. The regulatory approach of NBCD will have to take into consideration the specific characteristics of the drugs, their formulation and manufacturing process and the resulting critical attributes to achieve their desired quality, safety and efficacy. As with the biosimilars, for the NBCD product, family-specific methods should be evaluated and applied where scientifically proven, including sophisticated quality methods, pharmacodynamic markers and animal models. Concerning substitution and interchangeability of NBCD, it is also advisable to take biosimilars as an example, i.e. (1) substitution without the involvement of a healthcare professional should be discouraged to ensure traceability of the treatment of individual patients, (2) keep an individual patient on a specific treatment if the patient is doing well and only switch if unavoidable and (3) monitor the safety and efficacy of the new product if switching occurs.     

TREK-King the Blood–Brain-Barrier

TWIK-related potassium channel-1 (TREK1, KCNK2) is the most extensively studied member of the two-pore domain potassium (K_2P) channel family. Recent studies have already demonstrated a key role in the pathophysiology of depression, pain and neurodegenerative damage pointing towards an important role in a broad spectrum of CNS disorders. The mammalian blood–brain barrier (BBB) is a highly specialized structure and an integral part of the neurovascular unit, which controls the transition of cells and molecules into the CNS. While BBB dysregulation is common in neurologic diseases, the molecular mechanisms involved in this process remain largely unknown. Recently, we were able to describe a role of TREK1 in this context. TREK1 was downregulated in murine and human BBB upon inflammation. Blocking of TREK1 increased lymphocyte migration, while activation had the opposite effect. In TREK1-deficient (Trek1 ^?/? ) mice, brain endothelial cells displayed an inflammatory phenotype and leukocyte trafficking was facilitated, as demonstrated in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Here we summarize these findings and discuss the implications in diseases related to BBB dysfunction.     

Are our expectations bigger than the results we achieve? A comparative study analysing potential advantages of ankle arthroplasty over arthrodesis

Purpose

Prior studies have reported improved gait performance and kinematics after total ankle arthroplasty (TAR) compared to ankle arthrodesis (AAD). Given these findings, AAD has been primarily considered as a salvage procedure that may lead to adjacent joint degeneration.

Methods

A total of 101 TAR and 40 screw arthrodeses were enrolled in a retrospective study with a prospectively designed follow-up examination that included gait analysis and outcome assessment with the AOFAS hindfoot score and FAOS questionnaire.

Results

Significant asymmetry in gait and reduced range of motion compared to normal remained after both procedures. Subjective outcome improved after both procedures, and pain was significantly better after TAR. Limited functional gains after TAR and joint degeneration to the same degree after both procedures was seen in the mid-term. Hindfoot fusion seemed to have a greater impact on postoperative function than ankle arthrodesis.

Conclusion

Considering only minor functional gains of TAR compared to AAD the implantation of current TAR designs in large patient series may be questioned.