Is there a correlation between venlafaxine therapy during pregnancy and a higher incidence of necrotizing enterocolitis?

Background: Novel antidepressant drugs are increasingly used by women of child bearing age. However, potentially harmful effects on fetus and newborn remain unknown. Methods: Case report and literature review. Results: We present preterm twins whose mother was treated with venlafaxine, a nonselective serotonin reuptake inhibitor, throughout pregnancy until delivery. The twins developed neonatal necrotizing enterocolitis. Conclusion: The question whether there might be a correlation between maternal serotonin reuptake inhibitor therapy and neonatal necrotizing enterocolitis is discusse

Is there a correlation between venlafaxine therapy during pregnancy and a higher incidence of necrotizing enterocolitis?

Background: Novel antidepressant drugs are increasingly used by women of child bearing age. However, potentially harmful effects on fetus and newborn remain unknown. Methods: Case report and literature review. Results: We present preterm twins whose mother was treated with venlafaxine, a nonselective serotonin reuptake inhibitor, throughout pregnancy until delivery. The twins developed neonatal necrotizing enterocolitis. Conclusion: The question whether there might be a correlation between maternal serotonin reuptake inhibitor therapy and neonatal necrotizing enterocolitis is discusse

ESIN in Femur Fractures: Exact Technique Is Important!

Abstract : Background and Purpose: : Elastic stable intramedullary nailing (ESIN) is gaining increasing popularity, but studies with high case loads are rare. It was the aim of four experienced pediatric trauma centers to give an update of indications for ESIN, postoperative management, and complications. Patients and Methods: : Data of the last 100 ESIN cases of each department before June 30, 2003 were collected by reviewing the charts and X-rays. Among these 400 collected ESINs 65 femoral shaft fractures (16%) were found. The patients' age ranged between 23/4 and 151/4 years. The middle third of the shaft was affected 42 times (65%), 13 fractures (20%) were in the proximal third of the diaphysis, and ten (15%) in the distal part of the femur, five dia- and five metaphyseal. Mainly transverse fractures were treated (52%), followed by 38% oblique or spiral fractures and 10% wedge or comminuted fractures. Two open reductions were required. Median hospitalization time was 6 days. Nails were extracted after a mean of 178 days. Results: : Six skin irritations (wound infections, hematoma, seroma), one patient with myositis ossificans and one with constant pain at too long nail end were found. Three cosmetically relevant scarrings were observed during follow-up. Relevant axial deviations at fracture healing in two and shortening in one fracture could be seen, all caused by technical failure. Conclusion: : ESIN meets all demands for an optimal fracture healing in children. Still, a considerable percentage of complications is observed, mainly caused by the surgeon himself, which can be avoided by exact indication and technique. Postoperative management has yet to be standardize

The impact of the AO foundation on fracture care : an evaluation of 60 years AO foundation

Objectives Sixty years ago, the Association of Osteosynthesis (AO) was founded with the aim to improve fracture treatment and has since grown into one of the largest medical associations worldwide. Aim of this study was to evaluate AO's impact on science, education, patient care and the MedTech business. Design/methods Impact evaluations were conducted as appropriate for the individual domains: Impact on science was measured by analyzing citation frequencies of publications promoted by AO. Impact on education was evaluated by analyzing the evolution of number and location of AO courses. Impact on patient care was evaluated with a health economic model analyzing cost changes and years of life gained through the introduction of osteosynthesis in 17 high-income countries (HICs). Impact on MedTech business was evaluated by analyzing sales data of AO-associated products. Results Thirty-five AO papers and 2 major AO textbooks are cited at remarkable frequencies in high ranking journals with up to 2000 citations/year. The number of AO courses steadily increased with a total of 645'000 participants, 20‘000 teaching days and 2‘500 volunteer faculty members so far. The introduction of osteosynthesis saved at least 925 billion Swiss Francs [CHF] in the 17 HICs analyzed and had an impact on avoiding premature deaths comparable to the use of antihypertensive drugs. AO-associated products generated sales of 55 billion CHF. Conclusion AO's impact on science, education, patient care, and the MedTech business was significant because AO addressed hitherto unmet needs by combining activities that mutually enriched and reinforced each other

The additional labour of a disabled PhD student

This is a personal account of the challenges I have faced during the first year and a half of my PhD, solely due to my identity as a disabled student. I address issues such as a lack of representation when researching PhD life, the impact of the services which are meant to be there to help and the complexities of juggling the additional time-consuming events which occur when you are disabled, with PhD time, a home life and work. This is especially relevant in the United Kingdom at this time as the Disabled Students Allowance has recently been cut back, meaning there is less support available for disabled students, and with the increased marketisation of higher education it could be argued that there is less impetus for universities to support those who have non-standard needs

Patient-reported outcome measurements in clinical routine of trauma, spine and craniomaxillofacial surgeons: between expectations and reality: a survey among 1212 surgeons

Objective To gain information about the advantages/disadvantages of an implementation of patient-reported outcome measures (PROM) into the clinical routine of trauma/orthopaedic surgeons, and to identify the technical constraints confronting a successful implementation of PROMs. Design Online survey. Participants Surgeons who are members of the AO Foundation. Measures Participants answered questions regarding demographics, their familiarity with specific and generic PROMs and the use of PROMs in clinical routine. Furthermore, reasons for/against using PROMs, why not used more often, prerequisites to implement PROMs into clinical routine and whether PROMs would be implemented if adequate tools/technologies were available, were solicited. Χ2 tests and multivariable logistic regressions were conducted to evaluate the effect of the AO Region, surgeon specialisation, current position, clinical experience, and workplace on the familiarity with disease-specific PROMs, the familiarity with generic PROMs and the current use of PROMs. Exploratory factor analysis was used to identify issues underlying the extent of PROM usage. Results 1212 surgeons completed the survey (response rate: 6.8%; margin of error: ±2.72%): 54.2% were trauma/orthopaedic surgeons, 16.6% were spine surgeons, 27.9% were craniomaxillofacial surgeons and 16 had no defined specialty. Working in a certain AO Region, surgical specialisation and current workplace were associated with a higher familiarity of disease-specific PROMs and the use of PROMs in daily clinical routine (p≤0.05). Exploratory factor analysis identified four categories important for the use of PROMs and two categories preventing the use of PROMs. In case of the availability of an adequate tool, 66.2% of surgeons would implement PROMs in clinical routine. Conclusions Our survey results provide an understanding of the use of PROMs in clinical routine. There is consensus on the usefulness of PROMs. User-friendly and efficient tools/technologies would be a prerequisite for the daily use of PROMs. Additionally, educational efforts and/or policies might help

The Proteasome System in Infection: Impact of β5 and LMP7 on Composition, Maturation and Quantity of Active Proteasome Complexes

Proteasomes are the major enzyme complexes for non-lysosomal protein degradation in eukaryotic cells. Mammals express two sets of catalytic subunits: the constitutive subunits β1, β2 and β5 and the immunosubunits LMP2 (β1i), MECL-1 (β2i) and LMP7 (β5i). The LMP7-propeptide (proLMP7) is required for optimal maturation of LMP2/MECL-1-containing precursors to mature immunoproteasomes, but can also mediate efficient integration into mixed proteasomes containing β1 and β2. In contrast, the β5-propeptide (proβ5) has been suggested to promote preferential integration into β1/β2-containing precursors, consequently favouring the formation of constitutive proteasomes. Here, we show that proβ5 predominantly promotes integration into LMP2/MECL-1-containing precursors in IFNγ-stimulated, LMP7-deficient cells and infected LMP7-deficient mice. This demonstrates that proβ5 does not direct preferential integration into β1/β2-containing precursors, but instead promotes the formation of mixed LMP2/MECL-1/β5 proteasomes under inflammatory conditions. Moreover, the propeptides substantially differ in their capacity to promote proteasome maturation, with proLMP7 showing a significantly higher chaperone activity as compared to proβ5. Increased efficiency of proteasome maturation mediated by proLMP7 is required for optimal MHC class I cell surface expression and is equally important as the catalytic activity of immunoproteasomes. Intriguingly, induction of LMP7 by infection not only results in rapid exchange of constitutive by immunosubunits, as previously suggested, but also increases the total proteasome abundance within the infected tissue. Hence our data identify a novel LMP7-dependend mechanism to enhance the activity of the proteasome system in infection, which is based on the high chaperone activity of proLMP7 and relies on accelerated maturation of active proteasome complexes

The AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF).

Background and purpose - To achieve a common understanding when dealing with long bone fractures in children, the AO Pediatric Comprehensive Classification of Long Bone Fractures (AO PCCF) was introduced in 2007. As part of its final validation, we present the most relevant fracture patterns in the lower extremities of a representative population of children classified according to the PCCF. Patients and methods - We included patients up to the age of 17 who were diagnosed with 1 or more long bone fractures between January 2009 and December 2011 at either of 2 tertiary care university hospitals in Switzerland. Patient charts were retrospectively reviewed. Results - More lower extremity fractures occurred in boys (62%, n = 341). Of 548 fractured long bones in the lower extremity, 25% involved the femur and 75% the lower leg. The older the patients, the more combined fractures of the tibia and fibula were sustained (adolescents: 50%, 61 of 123). Salter-Harris (SH) fracture patterns represented 66% of single epiphyseal fractures (83 of 126). Overall, 74 of the 83 SH patterns occurred in the distal epiphysis. Of all the metaphyseal fractures, 74 of 79 were classified as incomplete or complete. Complete oblique spiral fractures accounted for 57% of diaphyseal fractures (120 of 211). Of all fractures, 7% (40 of 548) were classified in the category "other", including 29 fractures that were identified as toddler's fractures. 5 combined lower leg fractures were reported in the proximal metaphysis, 40 in the diaphysis, 26 in the distal metaphysis, and 8 in the distal epiphysis. Interpretation - The PCCF allows classification of lower extremity fracture patterns in the clinical setting. Re-introduction of a specific code for toddler's fractures in the PCCF should be considered

Prevention of colitis-associated cancer by selective targeting of immunoproteasome subunit LMP7

Chronic inflammation is a well-known risk factor in development of intestinal tumorigenesis, although the exact mechanisms underlying development of colitis-associated cancer (CAC) still remain obscure. The activity and function of immunoproteasome has been extensively analyzed in the context of inflammation and infectious diseases. Here, we show that the proteasomal immunosubunit LMP7 plays an essential role in development of CAC. Mice devoid of LMP7 were resistant to chronic inflammation and formation of neoplasia, and developed virtually no tumors after AOM/DSS treatment. Our data reveal that LMP7 deficiency resulted in reduced expression of pro-tumorigenic chemokines CXCL1, CXCL2 and CXCL3 as well as adhesion molecule VCAM-1. As a consequence, an impaired recruitment and activity of tumor-infiltrating leukocytes resulting in decreased secretion of cytokines IL-6 and TNF-α was observed. Further, the deletion or pharmacological inhibition of LMP7 and consequent blockade of NF-κB abrogated the production of IL-17A, which possesses a strong carcinogenic activity in the gut. Moreover, in vivo administration of the selective LMP7 inhibitor ONX-0914 led to a marked reduction of tumor numbers in wild-type (WT) mice. Collectively, we identified the immunoproteasome as a crucial mediator of inflammation-driven neoplasia highlighting a novel potential therapeutic approach to limit colonic tumorigenesis