Spatiotemporal Proteomic Analysis of Stress Granule Disassembly Using APEX Reveals Regulation by SUMOylation and Links to ALS Pathogenesis.

Stress granules (SGs) are cytoplasmic assemblies of proteins and non-translating mRNAs. Whereas much has been learned about SG formation, a major gap remains in understanding the compositional changes SGs undergo during normal disassembly and under disease conditions. Here, we address this gap by proteomic dissection of the SG temporal disassembly sequence using multi-bait APEX proximity proteomics. We discover 109 novel SG proteins and characterize distinct SG substructures. We reveal dozens of disassembly-engaged proteins (DEPs), some of which play functional roles in SG disassembly, including small ubiquitin-like modifier (SUMO) conjugating enzymes. We further demonstrate that SUMOylation regulates SG disassembly and SG formation. Parallel proteomics with amyotrophic lateral sclerosis (ALS)-associated C9ORF72 dipeptides uncovered attenuated DEP recruitment during SG disassembly and impaired SUMOylation. Accordingly, SUMO activity ameliorated C9ORF72-ALS-related neurodegeneration in Drosophila. By dissecting the SG spatiotemporal proteomic landscape, we provide an in-depth resource for future work on SG function and reveal basic and disease-relevant mechanisms of SG disassembly.

A systematic proximity ligation approach to studying protein-substrate specificity identifies the substrate spectrum of the Ssh1 translocon.

Many cellular functions are carried out by protein pairs or families, providing robustness alongside functional diversity. For such processes, it remains a challenge to map the degree of specificity versus promiscuity. Protein-protein interactions (PPIs) can be used to inform on these matters as they highlight cellular locals, regulation and, in cases where proteins affect other proteins - substrate range. However, methods to systematically study transient PPIs are underutilized. In this study, we create a novel approach to systematically compare stable or transient PPIs between two yeast proteins. Our approach, Cel-lctiv (CELlular biotin-Ligation for Capturing Transient Interactions in vivo), uses high-throughput pairwise proximity biotin ligation for comparing PPIs systematically and in vivo. As a proof of concept, we studied the homologous translocation pores Sec61 and Ssh1. We show how Cel-lctiv can uncover the unique substrate range for each translocon allowing us to pinpoint a specificity determinator driving interaction preference. More generally, this demonstrates how Cel-lctiv can provide direct information on substrate specificity even for highly homologous proteins.

A toolbox for systematic discovery of stable and transient protein interactors in baker's yeast.

Identification of both stable and transient interactions is essential for understanding protein function and regulation. While assessing stable interactions is more straightforward, capturing transient ones is challenging. In recent years, sophisticated tools have emerged to improve transient interactor discovery, with many harnessing the power of evolved biotin ligases for proximity labelling. However, biotinylation-based methods have lagged behind in the model eukaryote, Saccharomyces cerevisiae, possibly due to the presence of several abundant, endogenously biotinylated proteins. In this study, we optimised robust biotin-ligation methodologies in yeast and increased their sensitivity by creating a bespoke technique for downregulating endogenous biotinylation, which we term ABOLISH (Auxin-induced BiOtin LIgase diminiSHing). We used the endoplasmic reticulum insertase complex (EMC) to demonstrate our approaches and uncover new substrates. To make these tools available for systematic probing of both stable and transient interactions, we generated five full-genome collections of strains in which every yeast protein is tagged with each of the tested biotinylation machineries, some on the background of the ABOLISH system. This comprehensive toolkit enables functional interactomics of the entire yeast proteome.

Femoral neck shortening as a sequela of internal fixation for femoral neck fractures and its effect on the coronal alignment of the limb: a pilot study.

INTRODUCTION: Femoral neck shortening is a common phenomenon following osteosynthesis for femoral neck fractures, which was shown to have a negative effect on hip function. There is paucity of literature on the effect of shortening on the ipsilateral limb mechanical axis and knee coronal alignment. We hypothesized that postoperative femoral neck shortening can alter the limb's mechanical axis into valgus. METHODS: Of 583 patients screened, 13 patients with severe neck shortening (< 10 mm) following femoral neck fracture fixation, were found eligible and agreed to participate. A full-length lower limb radiographs were obtained and radiographic parameters (offset, neck-shaft angle, HKA, mLPFA, mDLFA, mMPTFA, MAD, MAD-r) as well as functional scores were obtained. RESULTS: Statistically significant differences in mechanical axis deviation ratio (MAD-r) were found between the ipsilateral and the contralateral extremities (0.41 ± 0.16 versus 0.55 ± 0.11, p = 0.03). A correlation between femoral neck length differences and MAD was not statistically significant although a tendency towards lateral deviation of the mechanical axis was noted (r = - 0.5, p = 0.077). A negative correlation was found between a greater difference in the femoral neck length and the SF12 score, both in the physical and the mental parts (r = - 0.69, p = 0.008; r = - 0.58, p = 0.035, respectively). CONCLUSION: We found a more lateralized mechanical axis in limbs that demonstrated post-operative ipsilateral femoral neck severe shortening. These findings may provide a possible explanation and rationale for knee pain and perhaps for the development of knee osteoarthritis as a sequalae of femoral neck shortening. Further investigation and larger cohort, long-term studies are needed to further explore this hypothesis.

A piggybacking mechanism enables peroxisomal localization of the glyoxylate cycle enzyme Mdh2 in yeast.

Eukaryotic cells have evolved organelles that allow the compartmentalization and regulation of metabolic processes. Knowledge of molecular mechanisms that allow temporal and spatial organization of enzymes within organelles is therefore crucial for understanding eukaryotic metabolism. Here, we show that the yeast malate dehydrogenase 2 (Mdh2) is dually localized to the cytosol and to peroxisomes and is targeted to peroxisomes via association with Mdh3 and a Pex5-dependent piggybacking mechanism. This dual localization of Mdh2 contributes to our understanding of the glyoxylate cycle and provides a new perspective on compartmentalization of cellular metabolism, which is critical for the perception of metabolic disorders and aging.

Impact of Comorbidities on Hospitalization for Injuries in Riders of Electric Bikes and Powered Scooters: A Retrospective Cross-Sectional Study.

Background and Objectives: Injuries associated with electric bikes (E-bikes) and powered scooters (P-scooters) have increased yearly worldwide. We aimed to evaluate the impact of pre-existing comorbidities on the probability of hospitalization for injuries in riders of E-bikes and P-scooters. Materials and Methods: A retrospective cross-sectional study design was used. The cohort included patients referred to the emergency department (ED) of a tertiary medical center in 2014-2020 for injuries sustained while riding an E-bike or P-scooter. Data were collected from the medical files on demographics, clinical characteristics including pre-existing comorbidities and permanent use of medications, and injury characteristics. Findings were compared between patients referred for hospitalization from the ED and patients discharged home. Results: Of the 1234 patients who met the inclusion criteria, 202 (16.4%) had a prior medical condition and 167 (13.5%) were taking medication on a permanent basis. A significant relationship was found between hospitalization and having a medical condition (𝜒2(1) = 9.20, p = 0.002) or taking medication on a permanent basis (𝜒2(1) = 6.24, p = 0.01). Hospitalization for injuries was more likely in patients with a comorbidity (27.8%) than those without a comorbidity (15.5%), and in patients who were on permanent drug therapy (22.2%) than in patients who were not (12.9%). Surprisingly, anticoagulant intake specifically had no effect on the probability of hospital admission. Conclusions: Patients with comorbidities have a higher incidence of hospitalization for E-bike- and P-scooter-associated injuries. Therefore, physicians may take into account comorbidities for the effective management of this patient group's injuries.

Trends in the Incidence and Severity of Injuries Sustained by Riders of Electric Bikes and Powered Scooters: A Retrospective Cross-Sectional Study.

Background and Objectives: The worldwide increase in electric bike (E-bike) and powered scooter (P-scooter) use in recent years has been accompanied by an increase in associated injuries to riders. The aim of this study was to evaluate trends in the incidence and types of E-bikes and P-scooter-related injuries in riders evacuated to a tertiary ED. Materials and Methods: A retrospective cross-sectional design was used. The cohort included 1234 patients referred to the emergency department (ED) of a tertiary medical center in 2014-2020 for injuries sustained while riding an E-bike or P-scooter. Demographic, clinical, and injury data were collected from the medical files, and injury rates were evaluated over time. Results: The results showed that the annual number of ED visits by injured E-bike and P-scooter riders increased steadily over the study period concomitant with an increase in ED referrals for hospitalization, indicating severe injury. The upper and lower extremities were the most frequent anatomic sites of injury in every year of the study, with variations among the different age groups. Conclusions: Our findings suggest a need for safety regulations for riders who operate two-wheel powered vehicles, such as licensing requirements and mandatory protective gear, especially for anatomic sites most at risk.

Psoas Attenuation and Mortality of Elderly Patients Undergoing Nontraumatic Emergency Laparotomy.

BACKGROUND: Emergency laparotomy (EL) is an increasingly common procedure in the elderly. Factors associated with mortality in the subpopulation of frail patients have not been thoroughly investigated. Sarcopenia has been investigated as a surrogate for frailty and poor prognosis. Our primary aim was to evaluate the association between easily measured sarcopenia parameters and 30-day postoperative mortality in elderly patients undergoing EL. Length of stay (LOS) and admission to an intensive care unit were secondary end points. METHODS: We conducted a retrospective cohort study, over a 5-year period, of patients aged 65 y and older who underwent EL at a tertiary university hospital. Sarcopenia was evaluated on admission computed tomography scan by two methods, first by psoas muscle attenuation and second by the product of perpendicular cross-sectional diameters (PCSDs). The lowest quartile of PCSDs and attenuation were defined as sarcopenic and compared with the rest of the cohort. Attenuation was stratified for the use of contrast enhancement. Multivariant logistic regression was performed to determine independent risk factors. RESULTS: During the study period, 403 patients, older than 65 y, underwent EL. Of these, 283 fit the inclusion criteria and 65 (23%) patients died within 30 d of surgery. On bivariate analysis, psoas muscle attenuation, but not PCSDs, was found to be associated with 30-day mortality (OR = 2.43, 95% CI = 1.34-4.38, P = 0.003) and longer LOS (35.7 d versus 22.2 d, Δd 13.5, 95% CI = 6.4-20.7, P < 0.001). In a multivariate analysis, psoas muscle attenuation, but not PCSDs, was an independent risk factor for 30-day postoperative mortality (OR = 2.35, 95% CI = 1.16-4.76, P = 0.017) and longer LOS (Δd = 14.4, 95% CI = 7.7-21.0, P < 0.001). Neither of the sarcopenia parameters was associated with increased admission to an intensive care unit. DISCUSSION: Psoas muscle attenuation is an independent risk factor for 30-day postoperative mortality and LOS after EL in the elderly population. This measurement can inform clinicians about the operative risk and hospital resource utilization.

Urinary bladder injury during cesarean delivery: risk factors and the role of retrograde bladder filling.

INTRODUCTION AND HYPOTHESIS: Urinary bladder injury during cesarean delivery is an uncommon complication with substantial maternal morbidity. The aim of this study was to identify possible risk factors for bladder injury during cesarean delivery and to describe the role of retrograde bladder filling in the assessment of bladder wall integrity. METHODS: A retrospective cohort study at a large tertiary referral center. Women who underwent cesarean delivery between 2003 and 2017 were included. Women diagnosed with urinary bladder injury were compared to women who did not have such injuries. Data retrieved included demographic characteristics, general medical history, obstetric history and intra-partum and intra-operative data. Information regarding use of retrograde bladder filling intra-operatively was retrieved as well. RESULTS: During the study period, 21,177 cesarean deliveries were performed of which 68 (0.3%) cases of urinary bladder injury were identified. Two-thirds of injuries were located at the urinary bladder dome with the remaining third located at the posterior bladder wall. Most injuries were formed during uterine incision extension (60.0%) followed by peritoneal entry (22.0%). Following uni- and multivariate analyses, three parameters remained independent risk factors for bladder injury: urinary bladder adhesions, failed vacuum attempt prior to cesarean delivery and size of the uterine incision extension. In 15.4% of cases in which retrograde bladder filling was utilized following bladder repair, leakage of fluid was evident. CONCLUSION: Urinary bladder adhesions, failed vacuum attempt prior to cesarean delivery and size of uterine incision extension are independent risk factors for urinary bladder injury during cesarean delivery.

Protein Topology Prediction Algorithms Systematically Investigated in the Yeast Saccharomyces cerevisiae.

Membrane proteins perform a variety of functions, all crucially dependent on their orientation in the membrane. However, neither the exact number of transmembrane domains (TMDs) nor the topology of most proteins have been experimentally determined. Due to this, most scientists rely primarily on prediction algorithms to determine topology and TMD assignments. Since these can give contradictory results, single-algorithm-based predictions are unreliable. To map the extent of potential misanalysis, the predictions of nine algorithms on the yeast proteome are compared and it is found that they have little agreement when predicting TMD number and termini orientation. To view all predictions in parallel, a webpage called TopologYeast: http://www.weizmann.ac.il/molgen/TopologYeast was created. Each algorithm is compared with experimental data and a poor agreement is found. The analysis suggests that more systematic data on protein topology are required to increase the training sets for prediction algorithms and to have accurate knowledge of membrane protein topology.

Iron affects Ire1 clustering propensity and the amplitude of endoplasmic reticulum stress signaling.

The unfolded protein response (UPR) allows cells to adjust secretory pathway capacity according to need. Ire1, the endoplasmic reticulum (ER) stress sensor and central activator of the UPR is conserved from the budding yeast Saccharomyces cerevisiae to humans. Under ER stress conditions, Ire1 clusters into foci that enable optimal UPR activation. To discover factors that affect Ire1 clustering, we performed a high-content screen using a whole-genome yeast mutant library expressing Ire1-mCherry. We imaged the strains following UPR induction and found 154 strains that displayed alterations in Ire1 clustering. The hits were enriched for iron and heme effectors and binding proteins. By performing pharmacological depletion and repletion, we confirmed that iron (Fe3+) affects UPR activation in both yeast and human cells. We suggest that Ire1 clustering propensity depends on membrane composition, which is governed by heme-dependent biosynthesis of sterols. Our findings highlight the diverse cellular functions that feed into the UPR and emphasize the cross-talk between organelles required to concertedly maintain homeostasis.

The Role of 18F-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography in the Diagnosis of Postoperative Hardware-Related Spinal Infections.

BACKGROUND: Implant-related spinal infections are a surgical complication associated with high morbidity. Due to infection, hardware removal may be necessary, which could lead to pseudarthrosis and the loss of stability and alignment. OBJECTIVES: To evaluate the accuracy and diagnostic value of 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) in the workup of patients with suspected implant-related infections of the spine and to assess the clinical impact of PET/CT results on the management of these infections. METHODS: The study included nine consecutive patients with a history of spinal surgery who underwent PET/CT for evaluation of suspected spinal implant related infection. All imaging studies were performed between January 2011 and December 2013. All 18F-FDG PET/CT scans were performed on an 8 slice PET/CT following an 18F-FDG injection. Images were scored both visually and semi-quantitatively by a radiology expert. Results were compared to additional imaging studies when available, which were correlated to clinical and bacteriological findings allowing calculation of sensitivity, specificity and accuracy. RESULTS: Among the patients, five experienced hardware-related spinal infection. 18F-FDG PET/CT sensitivity was 80%, specificity 100%, and accuracy 88.9%. One scan produced a false negative; however, a second PET/CT scan revealed an infection. CONCLUSIONS: PET/CT was found to be valuable for the diagnosis of postoperative hardware-related spinal infection, especially when other imaging modalities were uninformative or inconclusive. As such, PET/CT could be useful for management of infection treatment.

Atypical fractures of the femur related to prolonged treatment with bisphosphonates for osteoporosis.

BACKGROUND: Bisphosphonates reduce the overall risk of fractures among patients with osteoporosis, and this beneficial effect is long-lasting. However, since bisphosphonates inhibit bone remodeling, they may enhance the formation and propagation of micro-cracks over time and patients may therefore be prone to atypical fatigue fractures, mainly in the subtrochanteric region and femoral shaft. OBJECTIVES: To present two cases of subtrochanteric fractures related to bisphosphonate treatment, and review the current literature. CONCLUSIONS: Despite the overall beneficial effect of bisphosphonates, further research is required to prevent this significant complication.

Intramedullary nailing without curettage and cement augmentation for the treatment of impending and complete pathological fractures of the proximal or midshaft femur.

Metastases in the proximal femur and in the femoral diaphysis are usually treated with either cephalomedullary or intramedullary nailing. The benefit of curettage and augmentation of the nail with methyl methacrylate remains controversial. The authors retrospectively studied the outcomes with cephalomedullary and intramedullary nailing without curettage and methyl-methacrylate augmentation for lytic metastases of the proximal/diaphyseal femur. Twenty-one complete (11) or impending (10) pathological fractures in 19 consecutive patients were treated between January 2006 and August 2013. There were 11 women and 8 men. Their mean age was 62 years (range, 38 to 87). All patients received adjuvant chemotherapy or radiotherapy.The average postsurgical survival was 9.7 months (range 1-36 months). A single deep infection was debrided. Seventeen out of 19 patients were ambulatory, with or without a walking aid. No implant failure was noted. In other words, patients succumbed to the disease prior to hardware failure. Femoral nail insertion without curettage and cement augmentation provided satisfactory stabilization of proximal and diaphyseal femur fractures, impending or complete, even when there was massive bone destruction.

Changes in Sperm Parameters with Time in Men with Normal and Abnormal Baseline Semen Analysis.

The association between paternal age and sperm quality in the population level has been previously studied. Only limited data exists regarding the intra-personal variations in semen parameters among fertile and infertile men over time. We aimed to assess trends over time in semen parameters among men with normal and abnormal baseline sperm parameters and investigate potential risk factors for sperm quality deterioration. This retrospective cohort study was conducted at a university-affiliated medical center in vitro fertilization (IVF) unit. Patients with at least two semen analyses (SA) performed > 1 year apart, with the last SA done between 2017 and 2021, were included. The study consisted of two main analyses-comparison of intra-patient's sperm parameters changes in men with normal and abnormal baseline SA (BSA) and analysis of risk factors for developing abnormal semen parameters over time in men who had normal BSA parameters. This study included a total of 902 men assessed for infertility with normal and abnormal BSA. The average time interval between tests was 1015 days (range 366-7709 days). Among individuals with normal BSA, there was a mild decline in most parameters-concentration (- 6.53 M/ml), motility (- 7.74%), and total motile count (TMC) (- 21.80 M) (p < 0.05 for all parameters). In contrast, a slight improvement in most parameters, except for concentration, was noted in men with abnormal BSA-volume (+ 0.21 ml), motility (+ 8.72%), and TMC (+ 14.38 M) (p < 0.05 for all parameters). Focusing on men with normal BSA, 33.5% of individuals developed abnormality in one or more of their sperm parameters over time, within a mean time of 1013 ± 661 days. We also found that only time between tests emerged as an independent prognostic factor for the development of abnormal SA later. Interestingly, sperm deterioration in participants in their third, fourth, and fifth decades of life with normal initial semen analysis was similar. Our study provides evidence of a decline in semen quality over time in individuals with normal BSA, in contrast to men with abnormal BSA. Longer time intervals between tests independently increase the risk of sperm abnormalities.

Paternal high-fat diet affects weight and DNA methylation of their offspring.

Obesity poses a public health threat, reaching epidemic proportions. Our hypothesis suggests that some of this epidemic stems from its transmission across generations via paternal epigenetic mechanisms. To investigate this possibility, we focused on examining the paternal transmission of CpG methylation. First-generation male Wistar rats were fed either a high-fat diet (HF) or chow and were mated with females fed chow. We collected sperm from these males. The resulting offspring were raised on a chow diet until day 35, after which they underwent a dietary challenge. Diet-induced obese (DIO) male rats passed on the obesogenic trait to both male and female offspring. We observed significant hypermethylation of the Pomc promoter in the sperm of HF-treated males and in the hypothalamic arcuate nucleus (Arc) of their offspring at weaning. However, these differences in Arc methylation decreased later in life. This hypermethylation is correlated with increased expression of DNMT3B. Further investigating genes in the Arc that might be involved in obesogenic transgenerational transmission, using reduced representation bisulfite sequencing (RRBS) we identified 77 differentially methylated regions (DMRs), highlighting pathways associated with neuronal development. These findings support paternal CpG methylation as a mechanism for transmitting obesogenic traits across generations.

In Vitro Maturation of Oocytes Obtained from Ovarian Cortex Among Postpubertal Hematological Cancer Patients Undergoing Fertility Preservation.

Purpose: In vitro maturation (IVM) of oocytes obtained from ovarian tissue during ovarian tissue cryopreservation (OTC) is a technique for fertility preservation in patients with cancer obviating the need to postpone chemotherapy initiation. Little is known about IVM outcomes in hematological malignancies, especially post-chemotherapy. The purpose of this study was to evaluate the effect of cytotoxic treatment on the potential to retrieve immature oocytes and mature them in vitro and examine the association between serum inflammatory markers and these results. Methods: In this retrospective study, we evaluated inflammation markers, including B symptoms and IVM outcomes of 78 chemotherapy-naive and exposed patients diagnosed with Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), or acute myeloid leukemia (AML). Results: The mean number of oocytes found was 7.2 ± 7.2. The average number of oocytes matured by IVM was 2.8 ± 3.5, and a mean IVM rate was 32.1 ± 27.7%. All patients in the ALL and AML groups had previous exposure to chemotherapy before OTC, compared with 50.0% (7/14) and 31.9% (15/47) in the NHL and HL groups, respectively. Among patients with lymphoma, chemotherapy exposure was associated with the reduced number of retrieved oocytes (9.8 ± 7.7 vs. 5.3 ± 5.7 oocytes, p = 0.049) in the HL group but not with the number of mature oocytes or IVM rate. B symptoms were not associated with IVM outcomes. Lymphocyte count (ß = 1.584; p = 0.038) and lactate dehydrogenase (ß = 0.009; p = 0.043) were the only significant parameters associated with the number of matured oocytes in a linear regression model. Conclusion: IVM is a promising assisted reproductive technology, which holds great potential for patients in need of urgent fertility preservation or those who cannot receive hormonal stimulation. Our results demonstrate the feasibility of the technique even in the presence of B symptoms and elevated inflammation markers and in patients with previous exposure to chemotherapy.

A Similarity-Based Method for Predicting Enzymatic Functions in Yeast Uncovers a New AMP Hydrolase.

Despite decades of research and the availability of the full genomic sequence of the baker's yeast Saccharomyces cerevisiae, still a large fraction of its genome is not functionally annotated. This hinders our ability to fully understand cellular activity and suggests that many additional processes await discovery. The recent years have shown an explosion of high-quality genomic and structural data from multiple organisms, ranging from bacteria to mammals. New computational methods now allow us to integrate these data and extract meaningful insights into the functional identity of uncharacterized proteins in yeast. Here, we created a database of sensitive sequence similarity predictions for all yeast proteins. We use this information to identify candidate enzymes for known biochemical reactions whose enzymes are unidentified, and show how this provides a powerful basis for experimental validation. Using one pathway as a test case we pair a new function for the previously uncharacterized enzyme Yhr202w, as an extra-cellular AMP hydrolase in the NAD degradation pathway. Yhr202w, which we now term Smn1 for Scavenger MonoNucleotidase 1, is a highly conserved protein that is similar to the human protein E5NT/CD73, which is associated with multiple cancers. Hence, our new methodology provides a paradigm, that can be adopted to other organisms, for uncovering new enzymatic functions of uncharacterized proteins.

Age as a Predictive Factor in Severity of Injuries in Riders of Electric Bikes and Powered Scooters: A Retrospective Cross-Sectional Study.

The growth in worldwide popularity of electric bikes (E-bikes) and powered scooters (P-scooters) has been accompanied by an increase in injuries associated with their use. The aim of this study was to evaluate the contribution of rider age to injury severity, represented by need for hospitalization. A retrospective review of the database of a tertiary medical center yielded 1234 patients (75.7% male) who attended the emergency department (ED) in 2014−2020 for injuries sustained while riding an E-bike or P-scooter. Mean age was 31.52 ± 14.77 years: 23% were aged <20 years; 33%, 21−30 years; 23%, 31−40 years; 10%, 41−50 years; 11%, >51 years. Ninety patients (7.3%) were hospitalized. Older age was significantly associated with the need for hospitalization on univariate analysis (p <.001), but significance was not maintained on binary logistic regression (OR = 1.02, 95%CI 0.99−1.06; p = 0.11). Patients who underwent imaging evaluation in the ED were at lower risk of hospitalization, and patients who had surgery or a relatively long operative procedure were at higher risk of hospitalization. The study shows that older age (>51 years) is not associated with a significantly increased probability of severe injury in E-bike and P-scooter riders. This finding has important implications for insurers and healthcare administrators.

Efficacy of single-shot adductor canal block before Versus after primary total knee arthroplasty - Does timing make a difference? A randomized controlled trial.

BACKGROUND: Total knee arthroplasty (TKA) is associated with severe postoperative pain. Multimodal analgesia, including peripheral nerve block, is recommended for post-operative pain relief. Administration of some pain medications prior to surgery has shown to be more effective than after the operation. This is a prospective, randomized controlled trial designed to compare the analgesic efficacy of the adductor canal block (ACB) performed immediately before or immediately after primary total knee arthroplasty (TKA). We hypothesized that ACB before the surgery will reduce postoperative pain and improve knee function. METHODS: A total of 50 patients were enrolled and randomized into 2 groups, with 26 patients receiving a preoperative ACB and 24 receiving a postoperative ACB. RESULTS: Treatment groups were similar in terms of gender (p = .83), age (p = 0.61) weight (p = .39) and ASA score. Average visual analogue scale (VAS) on arrival to the post-anesthesia care unit (PACU) were 4.9 ± 3.2 in the preoperative ACB versus 3.4 ± 2.8 for the postoperative ACB (p = .075). VAS scores at different time points as well as the mean, minimal and maximal reported VAS scores were not significantly different between the two groups. The cumulative quantities of Fentanyl administered by the anesthesia team was comparable between the groups. Similarly, the dosage of Morphine, Tramadol, Acetaminophen and Dipyrone showed only small variations. The Quality of Recovery Score, Knee Society Scores and knee range of motion did not differ between the groups. CONCLUSIONS: Our findings demonstrate no significant differences in patient total narcotics consumption, pain scores and functional scores, between preoperative and postoperative ACB in patients undergoing TKA. TRIAL REGISTRATION: The trial was registered at www.clinicaltrials.gov and was assigned the registration number NCT02908711. LEVEL OF EVIDENCE: level I randomized controlled trial.