Broad-spectrum antibiotic prophylaxis in tumor and infected orthopedic surgery-the prospective-randomized, microbiologist-blinded, stratified, superiority trials: BAPTIST Trials.

BACKGROUND: The perioperative antibiotic prophylaxis with 1st or 2nd generation cephalosporins is evidence-based in orthopedic surgery. There are, however, situations with a high risk of prophylaxis-resistant surgical site infections (SSI). METHODS: We perform a superiority randomized controlled trial with a 10% margin and a power of 90% in favor of the broad-spectrum prophylaxis. We will randomize orthopedic interventions with a high risk for SSI due to selection of resistant pathogens (open fractures, surgery under therapeutic antibiotics, orthopedic tumor surgery, spine surgery with American Society of Anesthesiologists (ASA) score ≥ 3 points) in a prospective-alternating scheme (1:1, standard prophylaxis with cefuroxime versus a broad-spectrum prophylaxis of a combined single-shot of vancomycin 1 g and gentamicin 5 mg/kg parenterally). The primary outcome is "remission" at 6 weeks for most orthopedic surgeries or at 1 year for surgeries with implant. Secondary outcomes are the risk for prophylaxis-resistant SSI pathogens, revision surgery for any reason, change of antibiotic therapy during the treatment of infection, adverse events, and the postoperative healthcare-associated infections other than SSI within 6 weeks (e.g., urine infections or pneumonia). With event-free surgeries to 95% in the broad-spectrum versus 85% in the standard prophylaxis arm, we need 2 × 207 orthopedic surgeries. DISCUSSION: In selected patients with a high risk for infections due to selection of prophylaxis-resistant SSI, a broad-spectrum combination with vancomycin and gentamycin might prevent SSIs (and other postoperative infections) better than the prophylaxis with cefuroxime. TRIAL REGISTRATION: ClinicalTrial.gov NCT05502380. Registered on 12 August 2022. Protocol version: 2 (3 June 2022).

Increased cranio-caudal spinal cord oscillations are the cardinal pathophysiological change in degenerative cervical myelopathy.

Introduction: Degenerative cervical myelopathy (DCM) is the most common cause of non-traumatic incomplete spinal cord injury, but its pathophysiology is poorly understood. As spinal cord compression observed in standard MRI often fails to explain a patient's status, new diagnostic techniques to assess DCM are one of the research priorities. Minor cardiac-related cranio-caudal oscillations of the cervical spinal cord are observed by phase-contrast MRI (PC-MRI) in healthy controls (HCs), while they become pathologically increased in patients suffering from degenerative cervical myelopathy. Whether transversal oscillations (i.e., anterior-posterior and right-left) also change in DCM patients is not known. Methods: We assessed spinal cord motion simultaneously in all three spatial directions (i.e., cranio-caudal, anterior-posterior, and right-left) using sagittal PC-MRI and compared physiological oscillations in 18 HCs to pathological changes in 72 DCM patients with spinal canal stenosis. The parameter of interest was the amplitude of the velocity signal (i.e., maximum positive to maximum negative peak) during the cardiac cycle. Results: Most patients suffered from mild DCM (mJOA score 16 (14-18) points), and the majority (68.1%) presented with multisegmental stenosis. The spinal canal was considerably constricted in DCM patients in all segments compared to HCs. Under physiological conditions in HCs, the cervical spinal cord oscillates in the cranio-caudal and anterior-posterior directions, while right-left motion was marginal [e.g., segment C5 amplitudes: cranio-caudal: 0.40 (0.27-0.48) cm/s; anterior-posterior: 0.18 (0.16-0.29) cm/s; right-left: 0.10 (0.08-0.13) cm/s]. Compared to HCs, DCM patients presented with considerably increased cranio-caudal oscillations due to the cardinal pathophysiologic change in non-stenotic [e.g., segment C5 amplitudes: 0.79 (0.49-1.32) cm/s] and stenotic segments [.g., segment C5 amplitudes: 0.99 (0.69-1.42) cm/s]). In contrast, right-left [e.g., segment C5 amplitudes: non-stenotic segment: 0.20 (0.13-0.32) cm/s; stenotic segment: 0.11 (0.09-0.18) cm/s] and anterior-posterior oscillations [e.g., segment C5 amplitudes: non-stenotic segment: 0.26 (0.15-0.45) cm/s; stenotic segment: 0.11 (0.09-0.18) cm/s] remained on low magnitudes comparable to HCs. Conclusion: Increased cranio-caudal oscillations of the cervical cord are the cardinal pathophysiologic change and can be quantified using PC-MRI in DCM patients. This study addresses spinal cord oscillations as a relevant biomarker reflecting dynamic mechanical cord stress in DCM patients, potentially contributing to a loss of function.

Perioperative Urinary Catheter Use and Association to (Gram-Negative) Surgical Site Infection after Spine Surgery.

This study evaluates potential associations between the perioperative urinary catheter (UC) carriage and (Gram-negative) surgical site infections (SSIs) after spine surgery. It is a retrospective, single-center, case-control study stratifying group comparisons, case-mix adjustments using multivariate logistic regression analyses. Around half of the patients (2734/5485 surgeries) carried a UC for 1 day (median duration) (interquartile range, 1-1 days). Patients with perioperative UC carriage were compared to those without regarding SSI, in general, and Gram-negative, exclusively. The SSI rate was 1.2% (67/5485), yielding 67 revision surgeries. Gram-negative pathogens caused 16 SSIs. Seven Gram-negative episodes revealed the same pathogen concomitantly in the urine and the spine. In the multivariate analysis, the UC carriage duration was associated with SSI (OR 1.1, 95% confidence interval 1.1-1.1), albeit less than classical risk factors like diabetes (OR 2.2, 95%CI 1.1-4.2), smoking (OR 2.4, 95%CI 1.4-4.3), or higher ASA-Scores (OR 2.3, 95%CI 1.4-3.6). In the second multivariate analysis targeting Gram-negative SSIs, the female sex (OR 3.8, 95%CI 1.4-10.6) and a UC carriage > 1 day (OR 5.5, 95%CI 1.5-20.3) were associated with Gram-negative SSIs. Gram-negative SSIs after spine surgery seem associated with perioperative UC carriage, especially in women. Other SSI risk factors are diabetes, smoking, and higher ASA scores.

A Simple Preoperative Score Predicting Failure Following Decompression Surgery for Degenerative Lumbar Spinal Stenosis.

BACKGROUND CONTEXT: Proper patient selection is crucial for the outcome of surgically treated degenerative lumbar spinal stenosis (DLSS). Nevertheless, there is still not a clear consensus regarding the optimal treatment option for patients with DLSS. PURPOSE: To investigate the treatment failure rate and introduce a simple, preoperative score to aid surgical decision-making. STUDY DESIGN/SETTING: Retrospective observational study. PATIENT SAMPLE: Four hundred forty-five patients who underwent surgical decompression for DLSS. OUTCOME MEASURES: Treatment failure (defined as conversion to a fusion of a previously decompressed level) of lumbar decompression. MATERIALS AND METHODS: Several risk factors associated with worse outcomes and treatment failures, such as age, body mass index, smoking status, previous surgery, low back pain (LBP), facet joint effusion, disk degeneration, fatty infiltration of the paraspinal muscles, the presence of degenerative spondylolisthesis and the facet angulation, were investigated. RESULTS: At a mean follow-up of 44±31 months, 6.5% (29/445) of the patients underwent revision surgery with spinal fusion at an average of 3±9 months following the lumbar decompression due to low back or leg pain. The baseline LBP (≥7) [odds ratio (OR)=5.4, P <0.001], the presence of facet joint effusion (>2 mm) in magnetic resonance imaging (OR=4.2, P <0.001), and disk degeneration (Pfirrmann >4) (OR=3.2, P =0.03) were associated with an increased risk for treatment failure following decompression for DLSS. The receiver operating characteristic curve analysis demonstrated that a score≥6 points yielded a sensitivity of 90% and specificity of 64% for predicting a treatment failure following lumbar decompression for DLSS in the present cohort. CONCLUSIONS: The newly introduced score quantifying amounts of LBP, facet effusions, and disk degeneration, could predict treatment failure and the need for revision surgery for DLSS patients undergoing lumbar decompression without fusion. Patients with scores >6 have a high chance of needing fusion following decompression surgery. LEVEL OF EVIDENCE: Retrospective observational study, Level III.

The effect of lumbar spinal fusion on native acetabular anteinclination in standing position.

PURPOSE: The complex and dynamic spinopelvic interplay is not well understood. The aims of the present study were to investigate the following: (1) whether native acetabular anteinclination (AI) in standing position changes following lumbar spinal fusion (LSF); (2) potential correlations between AI change (ΔAI) and several spinopelvic parameters such as the change in lumbar lordosis (ΔLL), pelvic tilt (ΔPT), and anterior pelvic plane angle (ΔaPP). METHODS: A total of 485 patients (Males: 262, Females: 223) with an average age of 64 ± 13 years who underwent a primary LSF were identified from our institutional database. The difference (Δ) between pre-and postoperative acetabular anteinclination (AI), lumbar lordosis (LL), anterior pelvic plane angle (aPP), sacral slope (SS), and pelvic tilt (PT) were measured on a standing lateral radiograph (EOS®) and compared to find the effect of LSF on the lumbopelvic geometry. RESULTS: Following LSF, the average absolute ΔAI was 5.4 ± 4 (0 to 26)°, ΔLL: 5.5 ± 4 (0 to 27)°, ΔaPP: 5.4 ± 4 (0 to 38)°, ΔPT: 7 ± 5 (0 to 33)° and ΔSS: 5.3 ± 4 (0 to 33)°. No significant differences were observed between LSF levels. A ΔAI ≥ 10° was observed in 66 (13.6%) and ΔAI ≥ 20° in 5 (1%) patients. The Pearson correlation demonstrated a strong negative correlation of ΔAI with ΔLL (r = 0.72, p < .001). CONCLUSION: Clinical decision-making should consider the relationship between native anteinclination and lumbar lordosis to reduce the risk of functional acetabular component malalignment in patients with concomitant hip and spine pathology. LEVEL OF EVIDENCE: Retrospective case-control study, Level III.

Role of C-reactive protein in the bone marrow of Modic type 1 changes.

Modic type 1 changes (MC1) are vertebral bone marrow lesions and associate with low back pain. Increased serum C-reactive protein (CRP) has inconsistently been associated with MC1. We aimed to provide evidence for the role of CRP in the tissue pathophysiology of MC1 bone marrow. From 13 MC1 patients undergoing spinal fusion at MC1 levels, vertebral bone marrow aspirates from MC1 and intrapatient control bone marrow were taken. Bone marrow CRP, interleukin (IL)-1, and IL-6 were measured with enzyme-linked immunosorbent assays; lactate dehydrogenase (LDH) was measured with a colorimetric assay. CRP, IL-1, and IL-6 were compared between MC1 and control bone marrow. Bone marrow CRP was correlated with blood CRP and with bone marrow IL-1, IL-6, and LDH. CRP expression by marrow cells was measured with a polymerase chain reaction. Increased CRP in MC1 bone marrow (mean difference: +0.22 mg CRP/g, 95% confidence interval [CI] [-0.04, 0.47], p = 0.088) correlated with blood CRP (r = 0.69, p = 0.018), with bone marrow IL-1ß (ρ = 0.52, p = 0.029) and IL-6 (ρ = 0.51, p = 0.031). Marrow cells did not express CRP. Increased LDH in MC1 bone marrow (143.1%, 95% CI [110.7%, 175.4%], p = 0.014) indicated necrosis. A blood CRP threshold of 3.2 mg/L detected with 100% accuracy increased CRP in MC1 bone marrow. In conclusion, the association of CRP with inflammatory and necrotic changes in MC1 bone marrow provides evidence for a pathophysiological role of CRP in MC1 bone marrow.

Inhibition profile of trifludimoxazin towards PPO2 target site mutations.

BACKGROUND: Target site resistance to herbicides that inhibit protoporphyrinogen IX oxidase (PPO; EC 1.3.3.4) has been described mainly in broadleaf weeds based on mutations in the gene designated protoporphyrinogen oxidase 2 (PPO2) and in one monocot weed species in protoporphyrinogen oxidase 1 (PPO1). To control PPO target site resistant weeds in future it is important to design new PPO-inhibiting herbicides that can control problematic weeds expressing mutant PPO enzymes. In this study, we assessed the efficacy of a new triazinone-type inhibitor, trifludimoxazin, to inhibit PPO2 enzymes carrying target site mutations in comparison with three widely used PPO-inhibiting herbicides. RESULTS: Mutated Amaranthus spp. PPO2 enzymes were expressed in Escherichia coli, purified and measured biochemically for activity and inhibition kinetics, and used for complementation experiments in an E. coli hemG mutant that lacks the corresponding microbial PPO gene function. In addition, we used ectopic expression in Arabidopsis and structural PPO protein modeling to support the enzyme inhibition study. The generated data strongly suggest that trifludimoxazin is a strong inhibitor both at the enzyme level and in transgenics Arabidopsis ectopically expressing PPO2 target site mutations. CONCLUSION: Trifludimoxazin is a potent PPO-inhibiting herbicide that inhibits various PPO2 enzymes carrying target site mutations and could be used as a chemical-based control strategy to mitigate the widespread occurrence of PPO target site resistance as well as weeds that have evolved resistance to other herbicide mode of actions. © 2022 BASF SE and The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

CD90-positive stromal cells associate with inflammatory and fibrotic changes in modic changes.

Objective: Modic changes (MC) are vertebral bone marrow lesions seen on magnetic resonance images, that associate with disc degeneration and low back pain (LBP). Few studies described MC histopathology qualitatively based on a few patient samples. CD90-positive bone marrow stromal cells were shown to be pro-fibrotic in MC. We aimed to provide the first semi-quantitative histomorphometric analysis of MC bone marrow. We hypothesized a role of CD90-positive cells in MC pathomechanisms. Design: Human biopsies from Modic type 1 changes (MC1, n â€‹= â€‹8), Modic type 2 changes (MC2, n â€‹= â€‹6), and control biopsies (MC0, n â€‹= â€‹8) from adjacent vertebrae were obtained from 14 LBP patients during lumbar spinal fusion. Biopsies were processed for histology/immunohistochemistry. Inflammatory changes (oedema, inflammatory infiltrates), fibrotic changes (connective tissue, type I and III collagen, fibronectin, α-smooth muscle actin), and amount of bone marrow stromal cells (CD90, CD105) were scored. Scores for MC0, MC1, and MC2 were compared with non-parametric tests. Pairwise correlations, hierarchical clustering, and principal component analysis of histological readouts were calculated to identify most important histomorphometric MC characteristics. Results: Compared to MC0, MC1 had more connective tissue, oedema, inflammatory infiltrates, and CD90+ cells. MC2 compared to MC0 had more oedema and CD90+ cells. Scores of CD90 correlated and clustered with inflammatory and fibrotic changes. Amount of connective tissue correlated with LBP. Conclusion: Accumulation of CD90+ cells is a major characteristic of MC in patients undergoing lumbar spinal fusion and associates with inflammatory and fibrotic changes. Therefore, CD90+ cells may play an important role in the inflammatory-fibrotic pathomechanisms of MC.

County-Level Economic Changes and Drug Mortality in the United States: Evidence from the Great Recession.

We aimed at examining whether county-level economic changes were associated with changes in county-level drug mortality rates since the Great Recession and whether the association is equally distributed across major sociodemographic subgroups. Using the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (2004-2019), combined with census data, we conducted fixed effects analyses by including county-level economic changes as primary exposures and county-level drug-related mortality rates (per 100,000 people) from 2004-2007 (i.e., prior to the recession) to 2008-2011, 2012-2015, and 2016-2019 as an outcome variable based on 1833 counties. Our findings showed that drug mortality rates increased from 13.9 (2004-2007) to 16.0 (2008-2011), 18.0 (2012-2015), and 23.0 (2016-2019). Counties experiencing smaller median household income growth during and/or after the recession were associated with greater increase in drug mortality than counties experiencing larger median household income growth among the total population and all sociodemographic subgroups. Counties experiencing larger increases in unemployment rates and percentage of vacant housing units were associated with greater increase in drug mortality than counties experiencing smaller or no increase in unemployment rates and percentage of vacant housing units among certain sociodemographic subgroups. Findings suggest the importance of local economic contexts in understanding drug mortality risk since the recession. Drug overdose prevention polices need to be formulated by taking local economic changes following a major recession into consideration.

Involvement of glutamine synthetase 2 (GS2) amplification and overexpression in Amaranthus palmeri resistance to glufosinate.

MAIN CONCLUSION: Amplification and overexpression of the target site glutamine synthetase, specifically the plastid-located isoform, confers resistance to glufosinate in Amaranthus palmeri. This mechanism is novel among glufosinate-resistant weeds. Amaranthus palmeri has recently evolved resistance to glufosinate herbicide. Several A. palmeri populations from Missouri and Mississippi, U.S.A. had survivors when sprayed with glufosinate-ammonium (GFA, 657 g ha-1). One population, MO#2 (fourfold resistant) and its progeny (sixfold resistant), were used to study the resistance mechanism, focusing on the herbicide target glutamine synthetase (GS). We identified four GS genes in A. palmeri; three were transcribed: one coding for the plastidic protein (GS2) and two coding for cytoplasmic isoforms (GS1.1 and GS1.2). These isoforms did not contain mutations associated with resistance. The 17 glufosinate survivors studied showed up to 21-fold increase in GS2 copies. GS2 was expressed up to 190-fold among glufosinate survivors. GS1.1 was overexpressed > twofold in only 3 of 17, and GS1.2 in 2 of 17 survivors. GS inhibition by GFA causes ammonia accumulation in susceptible plants. Ammonia level was analyzed in 12 F1 plants. GS2 expression was negatively correlated with ammonia level (r = - 0.712); therefore, plants with higher GS2 expression are less sensitive to GFA. The operating efficiency of photosystem II (ϕPSII) of Nicotiana benthamiana overexpressing GS2 was four times less inhibited by GFA compared to control plants. Therefore, increased copy and overexpression of GS2 confer resistance to GFA in A. palmeri (or other plants). We present novel understanding of the role of GS2 in resistance evolution to glufosinate.

Comparison of axial and sagittal spinal cord motion measurements in degenerative cervical myelopathy.

BACKGROUND AND PURPOSE: The timing of decision-making for a surgical intervention in patients with mild degenerative cervical myelopathy (DCM) is challenging. Spinal cord motion phase contrast MRI (PC-MRI) measurements can reveal the extent of dynamic mechanical strain on the spinal cord to potentially identify high-risk patients. This study aims to determine the comparability of axial and sagittal PC-MRI measurements of spinal cord motion with the prospect of improving the clinical workup. METHODS: Sixty-four DCM patients underwent a PC-MRI scan assessing spinal cord motion. The agreement of axial and sagittal measurements was determined by means of intraclass correlation coefficients (ICCs) and Bland-Altman analyses. RESULTS: The comparability of axial and sagittal PC-MRI measurements was good to excellent at all cervical levels (ICCs motion amplitude: .810-.940; p < .001). Significant differences between axial and sagittal amplitude values could be found at segments C3 and C4, while its magnitude was low (C3: 0.07 ± 0.19 cm/second; C4: -0.12 ± 0.30 cm/second). Bland-Altman analysis showed a good agreement between axial and sagittal PC-MRI scans (coefficients of repeatability: minimum -0.23 cm/second at C2; maximum -0.58 cm/second at C4). Subgroup analysis regarding anatomic conditions (stenotic vs. nonstenotic segments) and different velocity encoding (2 vs. 3 cm/second) showed comparable results. CONCLUSIONS: This study demonstrates good comparability between axial and sagittal spinal cord motion measurements in DCM patients. To this end, axial and sagittal PC-MRI are both accurate and sensitive in detecting pathologic cord motion. Therefore, such measures could identify high-risk patients and improve clinical decision-making (ie, timing of decompression).

Incidence of Revision Surgery After Decompression With vs Without Fusion Among Patients With Degenerative Lumbar Spinal Stenosis.

Importance: Only limited data derived from large prospective cohort studies exist on the incidence of revision surgery among patients who undergo operations for degenerative lumbar spinal stenosis (DLSS). Objective: To assess the cumulative incidence of revision surgery after 2 types of index operations-decompression alone or decompression with fusion-among patients with DLSS. Design, Setting, and Participants: This cohort study analyzed data from a multicenter, prospective cohort study, the Lumbar Stenosis Outcome Study, which included patients aged 50 years or older with DLSS at 8 spine surgery and rheumatology units in Switzerland between December 2010 and December 2015. The follow-up period was 3 years. Data for this study were analyzed between October and November 2021. Exposures: All patients underwent either decompression surgery alone or decompression with fusion surgery for DLSS. Main Outcomes and Measures: The primary outcome was the cumulative incidence of revision operations. Secondary outcomes included changes in the following patient-reported outcome measures: Spinal Stenosis Measure (SSM) symptom severity (higher scores indicate more pain) and physical function (higher scores indicate more disability) subscale scores and the EuroQol Health-Related Quality of Life 5-Dimension 3-Level questionnaire (EQ-5D-3L) summary index score (lower scores indicate worse quality of life). Results: A total of 328 patients (165 [50.3%] men; median age, 73.0 years [IQR, 66.0-78.0 years]) were included in the analysis. Of these, 256 (78.0%) underwent decompression alone and 72 (22.0%) underwent decompression with fusion. The cumulative incidence of revisions after 3 years of follow-up was 11.3% (95% CI, 7.4%-15.1%) for the decompression alone group and 13.9% (95% CI, 5.5%-21.5%) for the fusion group (log-rank P = .60). There was no significant difference in the need for revision between the 2 groups over time (unadjusted absolute risk difference, 2.6% [95% CI, -6.3% to 11.4%]; adjusted absolute risk difference, 3.9% [95% CI, -5.2% to 17.0%]; adjusted hazard ratio, 1.40 [95% CI, 0.63-3.13]). The number of revisions was significantly associated with higher SSM symptom severity scores (ß, 0.171; 95% CI, 0.047-0.295; P = .007) and lower EQ-5D-3L summary index scores (ß, -0.061; 95% CI, -0.105 to -0.017; P = .007) but not with higher SSM physical function scores (ß, 0.068; 95% CI, -0.036 to 0.172; P = .20). The type of index operation was not significantly associated with the corresponding outcomes. Conclusions and Relevance: This cohort study showed no significant association between the type of index operation for DLSS-decompression alone or fusion-and the need for revision surgery or the outcomes of pain, disability, and quality of life among patients after 3 years. Number of revision operations was associated with more pain and worse quality of life.

Tooth for a tooth: Does fighting serve as a deterrent to greater violence in the modern NHL.

Fighting has been part of the fabric of the NHL for nearly a century. Recent sharp declines in the frequency of fighting and increased understanding of the long-term consequences of traumatic brain injuries have led many to question whether fighting still has a place in the modern NHL. League commissioner Gary Bettman as recently as 2019 testified before Canadian Parliament that fighting has a deterrent effect, reducing the overall level of violent and dangerous plays within the game. This study empirically examines this claim and tests whether fighting indeed serves as a deterrent to undesirable behaviors in the NHL. I examine data on all regular season penalties from 2010-2019 to determine whether fighting and the threat of fighting is empirically related the level of violence in NHL games. Using a mix of descriptive and quasi-experimental approaches, I find no quantifiable evidence that fighting serves as a deterrent to undesirable violent behaviors in the NHL. To the contrary, I find that teams and players who fight are responsible for a disproportionate amount of the violent penalties that happen across the league. These results have implications for player safety in the many professional-and especially junior-hockey leagues around the world that sanction in-game fighting.

Inhibition of acyl-ACP thioesterase as site of action of the commercial herbicides cumyluron, oxaziclomefone, bromobutide, methyldymron and tebutam.

BACKGROUND: Understanding the mode and site of action of a herbicide is key for its efficient development, the evaluation of its toxicological risk, efficient weed control and resistance management. Recently, the mode of action (MoA) of the herbicide cinmethylin was identified in lipid biosynthesis with acyl-ACP thioesterase (FAT) as the site of action (SoA). Cinmethylin was registered for selective use in cereal crops for the control of grass weeds in 2020. RESULTS: Here, we present a high-resolution co-crystal structure of FAT in complex with cumyluron identified by a high throughput crystallization screen. We show binding to and inhibition of FAT by cumyluron. Furthermore, in an array of experiments consisting of FAT binding assays, FAT inhibition assays, physiological and metabolic profiling, we tested compounds that are structurally related to cumyluron and identified the commercial herbicides oxaziclomefone, methyldymron, tebutam and bromobutide, with so far unknown sites of action, as FAT inhibitors. Additionally, we show that the previously described FAT inhibitors cinmethylin and methiozolin bind to FAT in a nanomolar range, inhibit FAT enzymatic activity and lead to similar metabolic changes. CONCLUSION: Based on presented data, we corroborate cinmethylin and methiozolin as potent FAT inhibitors and identify FAT as the SoA of the herbicides cumyluron, oxaziclomefone, bromobutide, methyldymron and tebutam. © 2022 Society of Chemical Industry.

Pelvic fixation in surgical correction of neuromuscular scoliosis.

Background: Surgical correction of neuromuscular scoliosis can be associated with high complication rates, including such associated with pelvic fixation. Up to now it is debated whether and when to include the pelvis into the fusion construct. Therefore, we aimed to illuminate when pelvic fixation is beneficial in surgical correction of neuromuscular scoliosis. Methods: A prospective cohort of 49 patients (mean age 13 ± 3 y, 63% females, follow up 56 months, range 24-215) who underwent correction of neuromuscular scoliosis including S1/the ileum (n = 18) or without (n = 31) pelvic fixation were included. The outcome was measured with analysis of radiological parameters, clinical improvement and complication/revision rates. Subgroup analysis was performed to find if non-ambulatory patients with gross motor function classification system (GMFCS) levels >III, with larger scoliotic curves (>60°) and moderate pelvic obliquities up to 35° benefit from pelvic fixation. Results: There was no significant difference in complications when comparing patients with (9 out of 18 patients, 50%) or without (9 out of 31 patients, 29%) fixation to the pelvis (p = .219). Wheelchair bound patients (GMFCS >III) with cobb angles greater than 60° and pelvic obliquity less than 35° (n = 20) revealed no differences in amount of clinical improvement of ambulation with (n = 9) or without (n = 11) pelvic fixation (p: n.s.). And even complication or revision rates where not different in those two groups. Conclusion: Pelvic fixation does not seem obligatory in wheelchair bound patients per definition. Even with pelvic obliquities up to 35° and large scoliotic curves >60°, avoiding pelvic fixation does not result in higher revision rate or worse clinical outcomes.

Can double PPO mutations exist in the same allele and are such mutants functional?

BACKGROUND: Resistance to protoporphyrinogen oxidase (PPO)-inhibiting herbicides is endowed primarily by target-site mutations at the PPX2 gene that compromise binding of the herbicide to the catalytic domain. In Amaranthus spp. PPX2, the most prevalent target mutations are deletion of the G210 codon, and the R128G and G339A substitutions. These mutations strongly affect the dynamic of the PPO2 binding pocket, resulting in reduced affinity with the ligand. Here we investigated the likelihood of co-occurrence of the most widespread target site mutations in the same PPX2 allele. RESULTS: Plants carrying R128G+/+ ΔG210+/-, where + indicates presence of the mutation, were crossed with each other. The PPX2 of the offspring was subjected to pyrosequencing and E. coli-based Sanger sequencing to determine mutation frequencies and allele co-occurrence. The data show that R128G ΔG210 can occur in one allele only; the second allele carries only one mutation. Double mutation in both alleles is less likely because of significant loss of enzyme activity. The segregation of offspring populations derived from a cross between heterozygous plants carrying ΔG210 G399A also showed no co-occurrence in the same allele. The offspring exhibited the expected mutation distribution patterns with few exceptions. CONCLUSIONS: Homozygous double-mutants are not physiologically viable. Double-mutant plants can only exist in a heterozygous state. Alternatively, if two mutations are detected in one plant, each mutation would occur in a separate allele. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Risk factors for L5 pedicle fractures after single-level posterior spinal fusion.

BACKGROUND CONTEXT: Pedicle fractures are a rare but potentially devastating complication of posterior instrumented spinal fusion (PSF). Preoperative awareness of the possible risk factors may help prevent these fractures by modifying the surgical plan. However, the risk factors have not yet been identified. PURPOSE: To determine the preoperative parameters associated with postoperative L5 pedicle fracture after L4/5 PSF. STUDY DESIGN: Case control study. PATIENT SAMPLE: Patients undergoing L4/5 PSF at a single academic institution between 2014 and 2020. OUTCOME MEASURES: Occurrence of postoperative L5 pedicle fracture. METHODS: Of 253 patients (female:male, 145:108) undergoing L4/5 PSF from 2014 to 2020, patients with postoperative L5 pedicle fractures were identified retrospectively as "cases" (n = 8, all female, age: 70 ± 10.7 years). As a control group all remaining patients with a follow-up of more than 12 months were allocated (n = 184, 104 females, age: 64.27 ± 13.00 years). In all but 16 cases, anterior support with transforaminal or posterior interbody fusion was performed. Demographic and clinical data (body mass index (BMI)), surgical factors, and comorbidities) were compared. Radiological assessment of spinopelvic parameters was performed using pre- and postoperative standing lateral radiographs. RESULTS: The overall incidence of L5 pedicle fractures after L4/5 spinal fusion was 3.16%, with a median time from index surgery to diagnosis of 25 days (range, 6-199 days) (75% within the first 32 days postoperatively). Patients with L5 pedicle fractures had higher pelvic incidence (PI) (71° ± 9° vs. 56° ± 11°; p=.001), sacral slope (SS) (45° ± 7° vs. 35° ± 8°; p=.002), L5 slope (30° ± 11° vs. 15° ± 10°, p=.001), L5 incidence (42° ± 14° vs. 26° ± 11°; p= .003), L1-S1 lumbar lordosis (LL) postop (57° ± 10° vs. 45° ± 11°; p=.006), and L4 -S1 LL postop (33° ± 7° vs. 28° ± 7°; p=.049) compared with the control group. Pelvic tilt and PI- LL mismatch were not significantly different. Female gender was a significant risk factor for L5 pedicle fractures (p=.015). BMI (kg/m2) was statistically equal in patients with or without pedicle fractures (28.37 ± 5.96 vs. 28.53 ± 16.32; p=.857). There was no significant difference between the groups for approximative bone mineral density assessment (Hounsfield units; 113 ± 60 vs. 120 ± 43; p=.396) using the L3 trabecular region of interest (ROI) measurement. The correlation analysis demonstrated that most of the identified risk factors except for the postoperative L4-S1 lordosis show significant positive associations among each other. All eight patients in the fracture group underwent revision surgery, and the instrumented fusion was extended to the sacrum, with the addition of sacral-alar-iliac or iliac screws, in six cases. CONCLUSIONS: L5 pedicle fractures occurred in 3% of the patients after single level L4/5 PSF. Risk factors are female gender, higher PI, SS, L5 slope, L5 incidence, and LL postop but not high BMI. These findings can be used for surgical planning and decision of fusion levels.

Intraoperative Monitoring of CSF Pressure in Patients with Degenerative Cervical Myelopathy (COMP-CORD Study): A Prospective Cohort Study.

Degenerative cervical myelopathy (DCM) is hallmarked by spinal canal narrowing and related cord compression and myelopathy. Cerebrospinal fluid (CSF) pressure dynamics are likely disturbed due to spinal canal stenosis. The study aimed to investigate the diagnostic value of continuous intraoperative CSF pressure monitoring during surgical decompression. This prospective single center study (NCT02170155) enrolled DCM patients who underwent surgical decompression between December 2019 and May 2021. Data from n = 17 patients were analyzed and symptom severity graded with the modified Japanese Orthopedic Score (mJOA). CSF pulsations were continuously monitored with a lumbar intrathecal catheter during surgical decompression. Mean patient age was 62 ± 9 years (range 38-73; 8 female), symptoms were mild-moderate in most patients (mean mJOA 14 ± 2, range 10-18). Measurements were well tolerated without safety concerns. In 15/16 patients (94%), CSF pulsations increased at the time of surgical decompression. In one case, responsiveness could not be evaluated for technical reasons. Unexpected CSF pulsation decrease was related to adverse events (i.e., CSF leakage). Median CSF pulsation amplitudes increased from pre-decompression (0.52 mm Hg, interquartile range [IQR] 0.71) to post-decompression (0.72 mm Hg, IQR 0.96; p = 0.001). Mean baseline CSF pressure increased with lower magnitude than pulsations, from 9.5 ± 3.5 to 10.3 ± 3.8 mm Hg (p = 0.003). Systematic relations of CSF pulsations were confined to surgical decompression, independent of arterial blood pressure (p = 0.927) or heart rate (p = 0.102). Intraoperative CSF pulsation monitoring was related to surgical decompression while in addition adverse events could be discerned. Further investigation of the clinical value of intraoperative guidance for decompression in complex DCM surgery is promising.

[18F]-sodium fluoride PET/MR for painful lumbar facet joint degeneration - a randomized controlled clinical trial.

BACKGROUND CONTEXT: [18F]-sodium fluoride (NaF) PET/MR is a modern diagnostic modality for imaging increased bone turnover. Its merits in detecting painful facet joint osteoarthritis in patients with lumbar back pain are unknown. PURPOSE: To perform a prospective randomized controlled study investigating [18F]-NaF PET/MR for detecting painful facet joints in comparison to the standard of care (SOC), including clinical examination and conventional MRI. STUDY DESIGN/SETTING: Randomized controlled clinical study. PATIENT SAMPLE: Thirty-nine patients. OUTCOME MEASURES: Visual analog pain scale (VAS) before and at several time points after facet joint infiltration. METHODS: Patients with low back pain and suspected facet joint osteoarthritis underwent lumbar [18F]-NaF PET/MR, besides conventional MRI and clinical examination. After randomization, they either received local anesthetics/ corticosteroid infiltration of facet joints as defined by clinical examination and conventional MRI (SOC), or according to the hot spots on PET/MR. VAS was documented at 15 minutes, 1 day, 1 week and 1 month after infiltration. Thirty-nine patients underwent PET/MR before the study was stopped due to new Good Manufacturing Practice requirement and new regulations by radiation protection authorities limiting staff radiation exposure during the production of this radiotracer. RESULTS: Significant pain reduction compared to baseline was shown at every timepoint in both groups, except at 1 month after infiltration in the SOC group. Pain levels did not differ between SOC (n=17) and PET/MR patients (n=12) before infiltration and at 15 minutes, 1 day, 1 week and 1 month after infiltration. No significant correlation was detected between the sum of the PET/MR activity and the initial pain scores or relative reduction of pain after 15 minutes. The constructed study groups of patients with infiltration of all facet joints being PET/MR-positive (n=18) had significantly less pain after 1 months than patients with infiltration in PET/MR-negative facet joints (n=11) (VAS: 4 [0, 9] vs. 7 [2, 10], p=.046). CONCLUSIONS: There is no correlation of pain to NaF activity nor a relevant superiority of [18F]-NaF PET/MR for identification of painful facet joints compared to the standard of care.