Long-term comparison of anterior (ALIF) versus transforaminal (TLIF) lumbar interbody fusion: a propensity score-matched register-based study.

PURPOSE: Anterior (ALIF) and transforaminal (TLIF) lumbar interbody fusion have shown similar clinical outcomes at short- and medium-term follow-ups. Possible advantages of ALIF in the long run could be better disc height and lumbar lordosis and reduced risk of adjacent segment disease. We aimed to study if ALIF could be associated with superior clinical outcomes than TLIF at long-term follow-up. METHODS: We analysed 535 patients treated with ALIF or TLIF of the L5-S1 spinal segment between 2007 and 2017 who completed long-term follow-up in a national spine registry database (NORspine). We defined treatment success after surgery as at least 30% improvement in Oswestry Disability Index (ODI) at long-term follow-up. Patients treated with ALIF and TLIF and who responded at long term were balanced by propensity score matching. The proportions of successfully treated patients within each group were compared by numbers and percentages with corresponding relative risk. RESULTS: The mean (95%CI) age of the total study population was 50 (49-51) years, and 264 (49%) were females. The mean (95%CI) preoperative ODI score was 40 (39-42), and 174 (33%) had previous spine surgery. Propensity score matching left 120 patients in each treatment group. At a median (95%CI) of 92 (88-97) months after surgery, we found no difference in proportions successfully treated patients with ALIF versus TLIF (68 (58%) versus 77 (65%), RR (95%CI) = 0.88 (0.72 to1.08); p = 0.237). CONCLUSIONS: This propensity score-matched national spine register study of patients treated with ALIF versus TLIF of the lumbosacral junction found no differences in proportions of successfully treated patients at long-term follow-up. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.

Postoperative complications after surgery for lumbar spinal stenosis, assessment using two different data sources.

PURPOSE: Lumbar spinal stenosis (LSS) is a prevalent disorder, and surgery for LSS is a common procedure. Postoperative complications occur after any surgery and impose costs for society and costs and additional morbidity for patients. Since complications are relatively rare, medical registries of large populations may provide valuable knowledge. However, recording of complications in registries can be incomplete. To better estimate the true prevalence of complications after LSS surgery, we reviewed two different sources of data and recorded complications for a sample of Norwegian LSS patients. METHODS: 474 patients treated surgically for LSS during 2015 and 2016 at four hospitals reported to a national spine registry (NORspine). Postoperative complications were recorded by patients in NORspine, and we cross-referenced complications documented in NORspine with the patients´ electronic patient records (EPR) to re-test the complication rates. We performed descriptive statistics of complication rates using the two different data sources above, and analyzed the association between postoperative complications and clinical outcome with logistic regression. RESULTS: The mean (95%CI) patient age was 66.3 (65.3-67.2) years, and 254 (53.6%) were females. All patients were treated with decompression, and 51 (10.7%) received an additional fusion during the index surgery. Combining the two data sources, we found a total rate for postoperative complications of 22.4%, the NORspine registry reported a complication rate of 15.6%, and the EPR review resulted in a complication rate of 16.0%. However, the types of complications were inconsistent across the two data sources. According to NORspine, the frequency of reoperation within 90 days was 0.9% and according to EPR 3.4%. The rates of wound infection were for NORspine 3.1% and EPR review 2.1%. There was no association between postoperative complication and patient reported outcome. CONCLUSION: Postoperative complications occurred in 22% of LSS patients. The frequency of different postoperative complications differed between the two data sources.

Characteristics and outcomes of patients who did not respond to a national spine surgery registry.

BACKGROUND: Loss to follow-up may bias outcome assessments in medical registries. This cohort study aimed to analyze and compare patients who failed to respond with those that responded to the Norwegian Registry for Spine Surgery (NORspine). METHODS: We analyzed a cohort of 474 consecutive patients operated for lumbar spinal stenosis at four public hospitals in Norway during a two-year period. These patients reported sociodemographic data, preoperative symptoms, and Oswestry Disability Index (ODI), numerical rating scales (NRS) for back and leg pain to NORspine at baseline and 12 months postoperatively. We contacted all patients who did not respond to NORspine after 12 months. Those who responded were termed responsive non-respondents and compared to 12 months respondents. RESULTS: One hundred forty (30%) did not respond to NORspine 12 months after surgery and 123 were available for additional follow-up. Sixty-four of the 123 non-respondents (52%) responded to a cross-sectional survey done at a median of 50 (36-64) months after surgery. At baseline, non-respondents were younger 63 (SD 11.7) vs. 68 (SD 9.9) years (mean difference (95% CI) 4.7 years (2.6 to 6.7); p = < 0.001) and more frequently smokers 41 (30%) vs. 70 (21%) RR (95%CI) = 1.40 (1.01 to 1.95); p = 0.044. There were no other relevant differences in other sociodemographic variables or preoperative symptoms. We found no differences in the effect of surgery on non-respondents vs. respondents (ODI (SD) = 28.2 (19.9) vs. 25.2 (18.9), MD (95%CI) = 3.0 ( -2.1 to 8.1); p = 0.250). CONCLUSION: We found that 30% of patients did not respond to NORspine at 12 months after spine surgery. Non-respondents were somewhat younger and smoked more frequently than respondents; however, there were no differences in patient-reported outcome measures. Our findings suggest that attrition bias in NORspine was random and due to non-modifiable factors.

Binding of human serum proteins to Plasmodium falciparum-infected erythrocytes and its association with malaria clinical presentation.

BACKGROUND: The pathogenesis of Plasmodium falciparum malaria is related to the ability of parasite­infected erythrocytes (IEs) to adhere to the vascular endothelium (cytoadhesion/sequestration) or to surrounding uninfected erythrocytes (rosetting). Both processes are mediated by the expression of members of the clonally variant PfEMP1 parasite protein family on the surface of the IEs. Recent evidence obtained with laboratory-adapted clones indicates that P. falciparum can exploit human serum factors, such as IgM and α2-macroglobulin (α2M), to increase the avidity of PfEMP1-mediated binding to erythrocyte receptors, as well as to evade host PfEMP1-specific immune responses. It has remained unclear whether PfEMP1 variants present in field isolates share these characteristics, and whether they are associated with clinical malaria severity. These issues were investigated here. METHODS: Children 1-12 years reporting with P. falciparum malaria to Hohoe Municipal Hospital, Ghana were enrolled in the study. Parasites from children with uncomplicated (UM) and severe malaria (SM) were collected. Binding of α2M and IgM from non-immune individuals to erythrocytes infected by P. falciparum isolates from 34 children (UM and SM) were analysed by flow cytometry. Rosetting in the presence of IgM or α2M was also evaluated. Experimental results were analysed according to the clinical presentation of the patients. RESULTS: Clinical data from 108 children classified as UM (n = 54) and SM cases (n = 54) were analysed. Prostration, severe malaria anaemia, and hyperparasitaemia were the most frequent complications. Three children were diagnosed with cerebral malaria, and one child died. Parasite isolates from UM (n = 14) and SM (n = 20) children were analysed. Most of the field isolates bound non-immune IgM (33/34), whereas the α2M-binding was less common (23/34). Binding of both non-immune IgM and α2M was higher but not significant in IEs from children with SM than from children with UM. In combination, IgM and α2M supported rosette formation at levels similar to that observed in the presence of 10% human serum. CONCLUSIONS: The results support the hypothesis that binding of non-immune IgM and/or α2M to IEs facilitates rosette formation and perhaps contributes to P. falciparum malaria severity.

Natural and Vaccine-Induced Acquisition of Cross-Reactive IgG-Inhibiting ICAM-1-Specific Binding of a Plasmodium falciparum PfEMP1 Subtype Associated Specifically with Cerebral Malaria.

Cerebral malaria (CM) is a potentially deadly outcome of Plasmodium falciparum malaria that is precipitated by sequestration of infected erythrocytes (IEs) in the brain. The adhesion of IEs to brain endothelial cells is mediated by a subtype of parasite-encoded erythrocyte membrane protein 1 (PfEMP1) that facilitates dual binding to host intercellular adhesion molecule 1 (ICAM-1) and endothelial protein receptor C (EPCR). The PfEMP1 subtype is characterized by the presence of a particular motif (DBLß_motif) in the constituent ICAM-1-binding DBLß domain. The rate of natural acquisition of DBLß_motif-specific IgG antibodies and the ability to induce such antibodies by vaccination are unknown, and the aim of this study was to provide such data. We used an enzyme-linked immunosorbent assay (ELISA) to measure DBLß-specific IgG in plasma from Ghanaian children with malaria. The ability of human immune plasma and DBLß-specific rat antisera to inhibit the interaction between ICAM-1 and DBLß was assessed using ELISA and in vitro assays of IE adhesion under flow. The acquisition of DBLß_motif-specific IgG coincided with age-specific susceptibility to CM. Broadly cross-reactive antibodies inhibiting the interaction between ICAM-1 and DBLß_motif domains were detectable in immune plasma and in sera of rats immunized with specific DBLß_motif antigens. Importantly, antibodies against the DBLß_motif inhibited ICAM-1-specific in vitro adhesion of erythrocytes infected by four of five P. falciparum isolates from cerebral malaria patients. We conclude that natural exposure to P. falciparum as well as immunization with specific DBLß_motif antigens can induce cross-reactive antibodies that inhibit the interaction between ICAM-1 and a broad range of DBLß_motif domains. These findings raise hope that a vaccine designed specifically to prevent CM is feasible.

OSC2 and CYP716A14v2 catalyze the biosynthesis of triterpenoids for the cuticle of aerial organs of Artemisia annua.

Artemisia annua is widely studied for its ability to accumulate the antimalarial sesquiterpenoid artemisinin. In addition to producing a variety of sesquiterpenoids, A. annua also accumulates mono-, di-, and triterpenoids, the majority of which are produced in the glandular trichomes. A. annua also has filamentous trichomes on its aerial parts, but little is known of their biosynthesis potential. Here, through a comparative transcriptome analysis between glandular and filamentous trichomes, we identified two genes, OSC2 and CYP716A14v2, encoding enzymes involved in the biosynthesis of specialized triterpenoids in A. annua. By expressing these genes in Saccharomyces cerevisiae and Nicotiana benthamiana, we characterized the catalytic function of these proteins and could reconstitute the specialized triterpenoid spectrum of A. annua in these heterologous hosts. OSC2 is a multifunctional oxidosqualene cyclase that produces α-amyrin, ß-amyrin, and δ-amyrin. CYP716A14v2 is a P450 belonging to the functionally diverse CYP716 family and catalyzes the oxidation of pentacyclic triterpenes, leading to triterpenes with a carbonyl group at position C-3, thereby providing an alternative biosynthesis pathway to 3-oxo triterpenes. Together, these enzymes produce specialized triterpenoids that are constituents of the wax layer of the cuticle covering the aerial parts of A. annua and likely function in the protection of the plant against biotic and abiotic stress.

Increased Plasmodium chabaudi malaria mortality in mice with nutritional iron deficiency can be reduced by short-term adjunctive iron supplementation.

BACKGROUND: Iron deficiency is the most widespread nutrient deficiency and an important cause of developmental impairment in children. However, some studies have indicated that iron deficiency can also protect against malaria, which is a leading cause of childhood morbidity and mortality in large parts of the world. This has rendered interventions against iron deficiency in malaria-endemic areas controversial. METHODS: The effect of nutritional iron deficiency on the clinical outcome of Plasmodium chabaudi AS infection in A/J mice and the impact of intravenous iron supplementation with ferric carboxymaltose were studied before and after parasite infection. Plasma levels of the iron status markers hepcidin and fibroblast growth factor 23 were measured in animals surviving and succumbing to malaria, and accompanying tissue pathology in the liver and the spleen was assessed. RESULTS: Nutritional iron deficiency was associated with increased mortality from P. chabaudi malaria. This increased mortality could be partially offset by carefully timed, short-duration adjunctive iron supplementation. Moribund animals were characterized by low levels of hepcidin and high levels of fibroblast growth factor 23. All infected mice had extramedullary splenic haematopoiesis, and iron-supplemented mice had visually detectable intracellular iron stores. CONCLUSIONS: Blood transfusions are the only currently available means to correct severe anaemia in children with malaria. The potential of carefully timed, short-duration adjunctive iron supplementation as a safe alternative should be considered.

Malaria causes long-term effects on markers of iron status in children: a critical assessment of existing clinical and epidemiological tools.

BACKGROUND: Most epidemiological studies on the interplay between iron deficiency and malaria risk classify individuals as iron-deficient or iron-replete based on inflammation-dependent iron markers and adjustment for inflammation by using C-reactive protein (CRP) or α-1-acid glycoprotein (AGP). The validity of this approach and the usefulness of fibroblast growth factor 23 (FGF23) as a proposed inflammation-independent iron marker were tested. METHODS: Conventional iron markers and FGF23 were measured in children with acute falciparum malaria and after 1, 2, 4, and 6 weeks. Children, who were transfused or received iron supplementation in the follow-up period, were excluded, and iron stores were considered to be stable throughout. Ferritin levels 6 weeks after admission were used as a reference for admission iron status and compared with iron markers at different time points. RESULTS: There were long-term perturbations in iron markers during convalescence from acute malaria. None of the tested iron parameters, including FGF23, were independent of inflammation. CRP and AGP normalized faster than ferritin after malaria episodes. CONCLUSION: Malaria may bias epidemiological studies based on inflammation-dependent iron markers. Better markers of iron status during and after inflammation are needed in order to test strategies for iron supplementation in populations at risk of malaria.

Bilateral symmetrical comparison of the proximal femur using 3D-CT models.

PURPOSE: Superimposed three-dimensional (3D)-models obtained from CT-images have been used to evaluate displacement of femoral neck fractures, but this method assumes symmetrical anatomy of normal femurs. The present study aimed to compare the spatial orientation of the left and right proximal femur, thus establishing if 3D models can be used as a reference standard for the evaluation of fracture displacement. METHODS: We generated 3D-CT-models of 20 patients with no skeletal pathology of the proximal femurs. Three observers independently determined the positions of the fovea and the femoral head, and a vector intersecting the centre points of the fovea and the femoral head defined the rotation. Differences in positions and rotations were determined by superimposing the 3D-CT-models of both femurs. RESULTS: The mean distance (95% CI) between positions of the left and right fovea was 3.1 mm (2.7-3.4) and between the left and right femoral head 2.8 mm (2.6-3.0). The minimal detectable change was 2.8 for the fovea and 2.3 for the femoral head, and the repeatability coefficients between 2.1-2.7 and 1.0-2.9, respectively. Mean difference in rotation of the femoral head was 6° (5.3-6.6) with a minimal detectable change of 8.8 and repeatability coefficients ranging from 5.8 to 10.0. CONCLUSIONS: Distances between the left and right femoral heads were larger than what could be explained by measurement error alone, suggesting that there may be minor side-to-side differences. However, these differences are small, and 3D-CT-models can be used as a reference standard to evaluate displacement of femoral neck fractures.

Preoperative posterior tilt of at least 20° increased the risk of fixation failure in Garden-I and -II femoral neck fractures.

Background and purpose - It has been suggested that preoperative posterior tilt of the femoral head may increase the risk of fixation failure in Garden-I and -II femoral neck fractures. To investigate this association, we studied a cohort of 322 such patients. Patients and methods - Patients treated with internal fixation between 2005 and 2012 were retrospectively identified using hospital records and the digital image bank. 2 raters measured the preoperative posterior tilt angle and categorized it into 3 groups: < 10°, 10-20°, and ≥ 20°. The inter-rater reliability (IRR) was determined. Patients were observed until September 2013 (with a minimum follow-up of 18 months) or until failure of fixation necessitating salvage arthroplasty. The risk of fixation failure was assessed using competing-risk regression analysis, adjusting for time to surgery. Results - Patients with a posterior tilt of ≥ 20° had a higher risk of fixation failure: 19% (8/43) as compared to 11% (14/127) in the 10-20° category and 6% (9/152) in the < 10° category (p = 0.03). Posterior tilt of ≥ 20° increased the risk of fixation failure, with an adjusted hazard ratio of 3.4 (95% CI: 1.3-8.9; p = 0.01). The interclass correlation coefficient for angular measurements of posterior tilt was 0.90 (95% CI: 0.87-0.92), and the IRR for the categorization of posterior tilt into 3 groups was 0.76 (95% CI: 0.69-0.81). Interpretation - Preoperative posterior tilt of ≥ 20° in Garden-I and -II femoral neck fractures increased the risk of fixation failure necessitating salvage arthroplasty. The reliability of the methods that we used to measure posterior tilt ranged from good to excellent.

Involvement of leptin receptors expression in proliferation and neoangiogenesis in colorectal carcinoma.

PURPOSE: This study tested whether there exists a correlation between leptin receptors (LEPR) expression with proliferation and neoangiogenesis in colorectal carcinoma. METHODS: Enrolled were 75 patients with colorectal carcinoma, who underwent surgical tumor resection. After routine histopathological preparation, sections 3-4 µm thick were prepared. Routine H&E and immunohistochemical ABC method with anti-LEPR, anti-Ki67 and anti-CD 105 antibodies were performed. RESULTS: Pronounced or moderate LEPR expression in colorectal carcinoma was found in 77.3% of the cases. Absence of expression of LEPR correlated with low rate of proliferation in 94.1% of the cases, while high proliferation rate showed 92% of the cases with pronounced LEPR expression. Low grade neoangiogenesis correlated with absence of LEPR expression in 88.2% of the cases. In 92% of the cases with pronounced LEPR expression, high rate of angiogenesis was observed. The LEPR expression correlated significantly (p<0.001) with proliferation index (proIDX) and neoangiogenesis index (mvdIDX). The corresponded correlation coefficients indicated considerable strength of association between variables (r=0.63 and r=0.66). CONCLUSION: Our results demonstrated that LEPR expression in colorectal carcinoma significantly corresponded to proliferation index of tumor cells and neoangiogenesis, which could have significant therapeutic and prognostic implications.

Differential transcriptome analysis of glandular and filamentous trichomes in Artemisia annua.

BACKGROUND: The medicinal plant Artemisia annua is covered with filamentous trichomes and glandular, artemisinin producing trichomes. A high artemisinin supply is needed at a reduced cost for treating malaria. Artemisinin production in bioreactors can be facilitated if a better insight is obtained in the biosynthesis of artemisinin and other metabolites. Therefore, metabolic activities of glandular and filamentous trichomes were investigated at the transcriptome level. RESULTS: By laser pressure catapulting, glandular and filamentous trichomes as well as apical and sub-apical cells from glandular trichomes were collected and their transcriptome was sequenced using Illumina RNA-Seq. A de novo transcriptome was assembled (Trinity) and studied with a differential expression analysis (edgeR).A comparison of the transcriptome from glandular and filamentous trichomes shows that MEP, MVA, most terpene and lipid biosynthesis pathways are significantly upregulated in glandular trichomes. Conversely, some transcripts coding for specific sesquiterpenoid and triterpenoid enzymes such as 8-epi-cedrol synthase and an uncharacterized oxidosqualene cyclase were significantly upregulated in filamentous trichomes. All known artemisinin biosynthesis genes are upregulated in glandular trichomes and were detected in both the apical and sub-apical cells of the glandular trichomes. No significant differential expression could be observed between the apical and sub-apical cells. CONCLUSIONS: Our results underscore the vast metabolic capacities of A. annua glandular trichomes but nonetheless point to the existence of specific terpene metabolic pathways in the filamentous trichomes. Candidate genes that might be involved in artemisinin biosynthesis are proposed based on their putative function and their differential expression level.

Predictors for failure after surgery for lumbar spinal stenosis: a prospective observational study.

BACKGROUND/CONTEXT: Some patients do not improve after surgery for lumbar spinal stenosis (LSS), and surgical treatment implies a risk for complications and deterioration. Patient selection is of paramount importance to improve the overall clinical results and identifying predictive factors for failure is central in this work. PURPOSE: We aimed to explore predictive factors for failure and worsening after surgery for LSS. STUDY DESIGN /SETTING: Retrospective observational study on prospectively collected data from a national spine registry with a 12-month follow-up. PATIENT SAMPLE: We analyzed 11,873 patients operated for LSS between 2007 and 2017 in Norway, included in the Norwegian registry for spine surgery (NORspine). Twelve months after surgery, 8919 (75.1%) had responded. OUTCOME MEASURES: Oswestry Disability Index (ODI) 12 months after surgery. METHODS: Predictors were assessed with uni- and multivariate logistic regression, using backward conditional stepwise selection and a significance level of 0.01. Failure (ODI>31) and worsening (ODI>39) were used as dependent variables. RESULTS: Mean (95%CI) age was 66.6 (66.4-66.9) years, and 52.1% were females. The mean (95%CI) preoperative ODI score was 39.8 (39.4-40.1). All patients had decompression, and 1494 (12.6%) had an additional fusion procedure. Twelve months after surgery, the mean (95%CI) ODI score was 23.9 (23.5-24.2), and 2950 patients (33.2%) were classified as failures and 1921 (21.6%) as worse. The strongest predictors for failure were duration of back pain > 12 months (OR [95%CI]=2.24 [1.93-2.60]; p<.001), former spinal surgery (OR [95%CI]=2.21 [1.94-2.52]; p<.001) and age>70 years (OR (95%CI)=1.97 (1.69-2.30); p<.001). Socioeconomic variables increased the odds of failure (ORs between 1.36 and 1.62). The strongest predictors for worsening were former spinal surgery (OR [95%CI]=2.04 [1.77-2.36]; p<.001), duration of back pain >12 months (OR [95%CI]=1.83 [1.45-2.32]; p<.001) and age >70 years (OR [95%CI]=1.79 [1.49-2.14]; p<.001). Socioeconomic variables increased the odds of worsening (ORs between 1.33-1.67). CONCLUSIONS: After surgery for LSS, 33% of the patients reported failure, and 22% reported worsening as assessed by ODI. Preoperative duration of back pain for longer than 12 months, former spinal surgery, and age above 70 years were the strongest predictors for increased odds of failure and worsening after surgery.

Impact of the number of previous lumbar operations on patient-reported outcomes after surgery for lumbar spinal stenosis or lumbar disc herniation.

Repeated lumbar spine surgery has been associated with inferior clinical outcomes. This study aimed to examine and quantify the impact of this association in a national clinical register cohort. This is a population-based study from the Norwegian Registry for Spine surgery (NORspine). We included 26,723 consecutive cases operated for lumbar spinal stenosis or lumbar disc herniation from January 2007 to December 2018. The primary outcome was the Oswestry Disability Index (ODI), presented as the proportions reaching a patient-acceptable symptom state (PASS; defined as an ODI raw score ≤ 22) and ODI raw and change scores at 12-month follow-up. Secondary outcomes were the Global Perceived Effect scale, the numerical rating scale for pain, the EuroQoL five-dimensions health questionnaire, occurrence of perioperative complications and wound infections, and working capability. Binary logistic regression analysis was conducted to examine how the number of previous operations influenced the odds of not reaching a PASS. The proportion reaching a PASS decreased from 66.0% (95% confidence interval (CI) 65.4 to 66.7) in cases with no previous operation to 22.0% (95% CI 15.2 to 30.3) in cases with four or more previous operations (p < 0.001). The odds of not reaching a PASS were 2.1 (95% CI 1.9 to 2.2) in cases with one previous operation, 2.6 (95% CI 2.3 to 3.0) in cases with two, 4.4 (95% CI 3.4 to 5.5) in cases with three, and 6.9 (95% CI 4.5 to 10.5) in cases with four or more previous operations. The ODI raw and change scores and the secondary outcomes showed similar trends. We found a dose-response relationship between increasing number of previous operations and inferior outcomes among patients operated for degenerative conditions in the lumbar spine. This information should be considered in the shared decision-making process prior to elective spine surgery.

Total Hip Arthroplasty Leads to Better Results After Low-Energy Displaced Femoral Neck Fracture in Patients Aged 55 to 70 Years: A Randomized Controlled Multicenter Trial Comparing Internal Fixation and Total Hip Arthroplasty.

BACKGROUND: The optimal treatment of displaced femoral neck fractures in patients 55 to 70 years old remains controversial. The aim of the present study was to assess the effect of closed reduction and internal fixation with cannulated screws (IF) compared with total hip arthroplasty (THA) on hip pain and function, with use of data for outcome measures, complications, and reoperations. METHODS: This multicenter randomized controlled trial included all patients 55 to 70 years old who presented with a low-energy displaced femoral neck fracture between December 2013 and December 2018. Patients were randomly allocated to undergo either IF or THA. The primary outcome was the Harris Hip Score (HHS) at 12 months postoperatively. Secondary outcomes were the HHS at 4 and 24 months postoperatively, Oxford Hip Score (OHS), Hip Disability and Osteoarthritis Outcome Score (HOOS), health-related quality of life (EQ-5D-3L [EuroQol 5 Dimensions 3 Levels] index score and EQ-VAS [visual analogue scale]), VAS for pain, and VAS for patient satisfaction at 4, 12, and 24 months postoperatively. Complications and reoperations were continuously monitored. The primary analyses were performed according to the intention-to-treat principle. RESULTS: A total of 102 patients with a mean (± standard deviation) age of 63.7 ± 4.2 years were allocated to IF (n = 51) or THA (n = 51). The mean difference in the primary outcome, the HHS at 12 months postoperatively (5.3; 95% confidence interval, 0.9 to 9.7; p = 0.017), was below the predefined minimal clinically important difference of 10 points. However, patients who underwent THA had a significantly higher HHS at 4 and 12 months, better OHS at 4 and 12 months, and better HOOS at 4, 12, and 24 months postoperatively. Patients who underwent THA also reported better health-related quality of life at 4 months postoperatively and reported greater satisfaction and less pain at 4 and 12 months postoperatively. A total of 26 patients in the IF group (51%; 95% confidence interval, 37% to 65%) and 2 patients in the THA group (4%; 95% confidence interval, 0.5% to 13%) underwent a major reoperation. CONCLUSIONS: In this randomized controlled trial, we showed that patients between 55 and 70 years old who underwent THA for a low-energy displaced femoral neck fracture experienced better outcomes than those who underwent closed reduction and internal fixation. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Dissection of the phytohormonal regulation of trichome formation and biosynthesis of the antimalarial compound artemisinin in Artemisia annua plants.

• Biosynthesis of the sesquiterpene lactone and potent antimalarial drug artemisinin occurs in glandular trichomes of Artemisia annua plants and is subjected to a strict network of developmental and other regulatory cues. • The effects of three hormones, jasmonate, gibberellin and cytokinin, were studied at the structural and molecular levels in two different A. annua chemotypes by microscopic analysis of gland development, and by targeted metabolite and transcript profiling. Furthermore, a genome-wide cDNA-amplified fragment length polymorphism (AFLP)-based transcriptome profiling was carried out of jasmonate-elicited leaves at different developmental stages. • Although cytokinin and gibberellin positively affected at least one aspect of gland formation, these two hormones did not stimulate artemisinin biosynthesis. Only jasmonate simultaneously promoted gland formation and coordinated transcriptional activation of biosynthetic gene expression, which ultimately led to increased sesquiterpenoid accumulation with chemotype-dependent effects on the distinct pathway branches. Transcriptome profiling revealed a trichome-specific fatty acyl- coenzyme A reductase, trichome-specific fatty acyl-CoA reductase 1 (TFAR1), the expression of which correlates with trichome development and sesquiterpenoid biosynthesis. • TFAR1 is potentially involved in cuticular wax formation during glandular trichome expansion in leaves and flowers of A. annua plants. Analysis of phytohormone-modulated transcriptional regulons provides clues to dissect the concerted regulation of metabolism and development of plant trichomes.

Demonstration of a narrow energy spread, ∼0.5 GeV electron beam from a two-stage laser wakefield accelerator.

Laser wakefield acceleration of electrons holds great promise for producing ultracompact stages of GeV scale, high-quality electron beams for applications such as x-ray free electron lasers and high-energy colliders. Ultrahigh intensity laser pulses can be self-guided by relativistic plasma waves (the wake) over tens of vacuum diffraction lengths, to give >1 GeV energy in centimeter-scale low density plasmas using ionization-induced injection to inject charge into the wake even at low densities. By restricting electron injection to a distinct short region, the injector stage, energetic electron beams (of the order of 100 MeV) with a relatively large energy spread are generated. Some of these electrons are then further accelerated by a second, longer accelerator stage, which increases their energy to ∼0.5 GeV while reducing the relative energy spread to <5% FWHM.

New trends in breast reconstruction.

BACKGROUND: Breast reconstruction (BR) after radical mastectomy is intended to recreate symmetrical natural-appearing breasts while preserving patient safety and quality of life. PURPOSE: To evaluate the esthetic results and the complications of various BR methods after radical mastectomy. PATIENTS AND METHOD: Between August 2006 and March 2010, 36 women underwent BR after mastectomy in our institution. Their charts were reviewed retrospectively to evaluate the results and complications. We used immediate BR for Stage I and IIa breast carcinoma, and delayed BR for stage IIb and III breast carcinoma. RESULTS: We performed a pedicled Transverse Rectus Abdominis Muscle flap in 13 cases, pedicled Latissimus Dorsi with silicone implant in 10 cases, free Deep Inferior Epigastric Perforator (DIEP) flap in 9 cases, and other procedures in four cases. The encountered complications were: total flap failure--one case, partial edge flap necrosis--three cases, donor area wound dehiscence--one case, seroma--one case, local infection--one case. DISCUSSION: Trends in BR in recent years focus more on free perforator flaps, with the DIEP flap being the leader. Internal mammary vessels are most often used as recipient vessels for anasthomoses. Immediate BR when indicated has better aesthetic results. In less well-developed countries, insurance companies do not cover implant expenses and the autologous procedures remain the best option.