A gut-derived metabolite alters brain activity and anxiety behaviour in mice.

Integration of sensory and molecular inputs from the environment shapes animal behaviour. A major site of exposure to environmental molecules is the gastrointestinal tract, in which dietary components are chemically transformed by the microbiota1 and gut-derived metabolites are disseminated to all organs, including the brain2. In mice, the gut microbiota impacts behaviour3, modulates neurotransmitter production in the gut and brain4,5, and influences brain development and myelination patterns6,7. The mechanisms that mediate the gut-brain interactions remain poorly defined, although they broadly involve humoral or neuronal connections. We previously reported that the levels of the microbial metabolite 4-ethylphenyl sulfate (4EPS) were increased in a mouse model of atypical neurodevelopment8. Here we identified biosynthetic genes from the gut microbiome that mediate the conversion of dietary tyrosine to 4-ethylphenol (4EP), and bioengineered gut bacteria to selectively produce 4EPS in mice. 4EPS entered the brain and was associated with changes in region-specific activity and functional connectivity. Gene expression signatures revealed altered oligodendrocyte function in the brain, and 4EPS impaired oligodendrocyte maturation in mice and decreased oligodendrocyte-neuron interactions in ex vivo brain cultures. Mice colonized with 4EP-producing bacteria exhibited reduced myelination of neuronal axons. Altered myelination dynamics in the brain have been associated with behavioural outcomes7,9-14. Accordingly, we observed that mice exposed to 4EPS displayed anxiety-like behaviours, and pharmacological treatments that promote oligodendrocyte differentiation prevented the behavioural effects of 4EPS. These findings reveal that a gut-derived molecule influences complex behaviours in mice through effects on oligodendrocyte function and myelin patterning in the brain.

Integrated Multi-Cohort Analysis of the Parkinson's Disease Gut Metagenome.

BACKGROUND: The gut microbiome is altered in several neurologic disorders, including Parkinson's disease (PD). OBJECTIVES: The aim is to profile the fecal gut metagenome in PD for alterations in microbial composition, taxon abundance, metabolic pathways, and microbial gene products, and their relationship with disease progression. METHODS: Shotgun metagenomic sequencing was conducted on 244 stool donors from two independent cohorts in the United States, including individuals with PD (n = 48, n = 47, respectively), environmental household controls (HC, n = 29, n = 30), and community population controls (PC, n = 41, n = 49). Microbial features consistently altered in PD compared to HC and PC subjects were identified. Data were cross-referenced to public metagenomic data sets from two previous studies in Germany and China to determine generalizable microbiome features. RESULTS: We find several significantly altered taxa between PD and controls within the two cohorts sequenced in this study. Analysis across global cohorts returns consistent changes only in Intestinimonas butyriciproducens. Pathway enrichment analysis reveals disruptions in microbial carbohydrate and lipid metabolism and increased amino acid and nucleotide metabolism in PD. Global gene-level signatures indicate an increased response to oxidative stress, decreased cellular growth and microbial motility, and disrupted intercommunity signaling. CONCLUSIONS: A metagenomic meta-analysis of PD shows consistent and novel alterations in functional metabolic potential and microbial gene abundance across four independent studies from three continents. These data reveal that stereotypic changes in the functional potential of the gut microbiome are a consistent feature of PD, highlighting potential diagnostic and therapeutic avenues for future research. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Global metabolic profiles in a non-human primate model of maternal immune activation: implications for neurodevelopmental disorders.

Epidemiological evidence implicates severe maternal infections as risk factors for neurodevelopmental disorders, such as ASD and schizophrenia. Accordingly, animal models mimicking infection during pregnancy, including the maternal immune activation (MIA) model, result in offspring with neurobiological, behavioral, and metabolic phenotypes relevant to human neurodevelopmental disorders. Most of these studies have been performed in rodents. We sought to better understand the molecular signatures characterizing the MIA model in an organism more closely related to humans, rhesus monkeys (Macaca mulatta), by evaluating changes in global metabolic profiles in MIA-exposed offspring. Herein, we present the global metabolome in six peripheral tissues (plasma, cerebrospinal fluid, three regions of intestinal mucosa scrapings, and feces) from 13 MIA and 10 control offspring that were confirmed to display atypical neurodevelopment, elevated immune profiles, and neuropathology. Differences in lipid, amino acid, and nucleotide metabolism discriminated these MIA and control samples, with correlations of specific metabolites to behavior scores as well as to cytokine levels in plasma, intestinal, and brain tissues. We also observed modest changes in fecal and intestinal microbial profiles, and identify differential metabolomic profiles within males and females. These findings support a connection between maternal immune activation and the metabolism, microbiota, and behavioral traits of offspring, and may further the translational applications of the MIA model and the advancement of biomarkers for neurodevelopmental disorders such as ASD or schizophrenia.

3D bioprinting using stem cells.

Recent advances have allowed for three-dimensional (3D) printing technologies to be applied to biocompatible materials, cells and supporting components, creating a field of 3D bioprinting that holds great promise for artificial organ printing and regenerative medicine. At the same time, stem cells, such as human induced pluripotent stem cells, have driven a paradigm shift in tissue regeneration and the modeling of human disease, and represent an unlimited cell source for tissue regeneration and the study of human disease. The ability to reprogram patient-specific cells holds the promise of an enhanced understanding of disease mechanisms and phenotypic variability. 3D bioprinting has been successfully performed using multiple stem cell types of different lineages and potency. The type of 3D bioprinting employed ranged from microextrusion bioprinting, inkjet bioprinting, laser-assisted bioprinting, to newer technologies such as scaffold-free spheroid-based bioprinting. This review discusses the current advances, applications, limitations and future of 3D bioprinting using stem cells, by organ systems.

α-Synuclein Overexpression and the Microbiome Shape the Gut and Brain Metabolome in Mice.

Pathological forms of the protein α-synuclein contribute to a family of disorders termed synucleinopathies, which includes Parkinson's disease (PD). Most cases of PD are believed to arise from gene-environment interactions. Microbiome composition is altered in PD, and gut bacteria are causal to symptoms and pathology in animal models. To explore how the microbiome may impact PD-associated genetic risks, we quantitatively profiled nearly 630 metabolites from 26 biochemical classes in the gut, plasma, and brain of α-synuclein-overexpressing (ASO) mice with or without microbiota. We observe tissue-specific changes driven by genotype, microbiome, and their interaction. Many differentially expressed metabolites in ASO mice are also dysregulated in human PD patients, including amine oxides, bile acids and indoles. Notably, levels of the microbial metabolite trimethylamine N-oxide (TMAO) strongly correlate from the gut to the plasma to the brain, identifying a product of gene-environment interactions that may influence PD-like outcomes in mice. TMAO is elevated in the blood and cerebral spinal fluid of PD patients. These findings uncover broad metabolomic changes that are influenced by the intersection of host genetics and the microbiome in a mouse model of PD.

Gut microbiota suppress feeding induced by palatable foods.

Feeding behaviors depend on intrinsic and extrinsic factors including genetics, food palatability, and the environment.1,2,3,4,5 The gut microbiota is a major environmental contributor to host physiology and impacts feeding behavior.6,7,8,9,10,11,12 Here, we explored the hypothesis that gut bacteria influence behavioral responses to palatable foods and reveal that antibiotic depletion (ABX) of the gut microbiota in mice results in overconsumption of several palatable foods with conserved effects on feeding dynamics. Gut microbiota restoration via fecal transplant into ABX mice is sufficient to rescue overconsumption of high-sucrose pellets. Operant conditioning tests found that ABX mice exhibit intensified motivation to pursue high-sucrose rewards. Accordingly, neuronal activity in mesolimbic brain regions, which have been linked with motivation and reward-seeking behavior,3 was elevated in ABX mice after consumption of high-sucrose pellets. Differential antibiotic treatment and functional microbiota transplants identified specific gut bacterial taxa from the family S24-7 and the genus Lactobacillus whose abundances associate with suppression of high-sucrose pellet consumption. Indeed, colonization of mice with S24-7 and Lactobacillus johnsonii was sufficient to reduce overconsumption of high-sucrose pellets in an antibiotic-induced model of binge eating. These results demonstrate that extrinsic influences from the gut microbiota can suppress the behavioral response toward palatable foods in mice.

Dedicated orthopaedic elective unit: our experience from a district general hospital.

INTRODUCTION: The significance of ring-fencing orthopaedic beds and protected elective sites has recently been highlighted by the British Orthopaedic Association and the Royal College of Surgeons. During the pandemic, many such elective setups were established. This study aimed to compare the functioning and efficiency of an orthopaedic protected elective surgical unit (PESU) instituted during the pandemic with the pre-pandemic elective service at our hospital. METHODS: We retrospectively collected data of all patients who underwent elective orthopaedic procedures in PESU during the pandemic and a similar cohort of patients operated on via the routine elective service immediately prior to the pandemic. To minimise the effect of confounding factors, a secondary analysis was undertaken comparing total hip replacements by a single surgeon via PESU and pre-pandemic ward (PPW) over 5 months. RESULTS: A total of 192 cases were listed on PESU during the studied period whereas this number was 339 for PPW. However, more than half of those listed for a surgery on PPW were cancelled and only 162 cases were performed. PESU had a significantly better conversion rate with only 12.5% being cancelled. Forty-nine percent (87 out of 177) of the cases cancelled on PPW were due to a 'bed unavailability'. A further 17% (30/177) and 16% (28/177) were cancelled due to 'emergency case prioritisation' and 'patient deemed unfit', respectively. In contrast, only 3 out of the 24 patients cancelled on PESU were due to bed unavailability. Single-surgeon total hip replacement showed similar demographic features for the 25 patients on PESU and 37 patients on PPW. The patients on PESU also demonstrated a decrease in length of hospital stay with an average of 3 days.

Predictive value of post-void residual volume as an adjunctive tool in the clinical evaluation of cauda equina syndrome.

The early diagnosis of cauda equina syndrome (CES) is crucial for a favourable outcome. Several studies have reported the use of an ultrasound scan of the bladder as an adjunct to assess the minimum post-void residual volume of urine (mPVR). However, variable mPVR values have been proposed as a threshold without consensus on a value for predicting CES among patients with relevant symptoms and signs. The aim of this study was to perform a meta-analysis and systematic review of the published evidence to identify a threshold mPVR value which would provide the highest diagnostic accuracy in patients in whom the diagnosis of CES is suspected. The search strategy used electronic databases (PubMed, Medline, EMBASE, and AMED) for publications between January 1996 and November 2021. All studies that reported mPVR in patients in whom the diagnosis of CES was suspected, followed by MRI, were included. A total of 2,115 studies were retrieved from the search. Seven fulfilled the inclusion criteria. These included 1,083 patients, with data available from 734 being available for meta-analysis. In 125 patients, CES was confirmed by MRI. The threshold value of mPVR reported in each study varied and could be categorized into 100 ml, 200 ml, 300 ml, and 500 ml. From the meta-analysis, 200 ml had the highest diagnostic accuracy, with 82% sensitivity (95% confidence interval (CI) 0.72 to 0.90) and 65% specificity (95% CI 0.70 to 0.90). When compared using summative receiver operating characteristic curves, mPVR of 200 ml was superior to other values in predicting the radiological confirmation of CES. mPVR is a useful tool when assessing patients in whom the diagnosis of CES is suspected. Compared with other values a mPVR of 200 ml had superior sensitivity, specificity, and positive and negative predictive values. In a patient with a suggestive history and clinical findings, a mPVR of > 200 ml should further raise the suspicion of CES. Caution is recommended when considering the mPVR in isolation and using it as an 'exclusion tool', and it should only be used as an adjunct to a full clinical assessment.

Has the ProFHER Trial Changed the Orthopaedic Surgeons' Decision Making and Treatment of Proximal Humeral Fractures?

BACKGROUND: To explore the impact of the ProFHER trial on initial decision making in the management of proximal humerus fractures at a district general hospital (DGH). MATERIAL AND METHODS: Retrospective review of all proximal humerus fractures at a single DGH during 1 year before ProFHER (2014) and 1 year following publication (2018). Data related to demographics, fracture pattern, and management was collected from electronic patient records and analysed. RESULTS: 52 patients in 2014 and 70 patients in 2018 met the inclusion criteria. There was no significant difference in demographics or fracture classification. Fewer patients were admitted from Accident and Emergency in 2018 (44% vs 55%). Of patients admitted, there was no significant difference between the proportion referred to a shoulder surgeon (SS) (27.5% vs 30%). In patients seen initially in fracture clinic by a non-shoulder surgeon (NSS), significantly fewer were referred for a SS opinion in 2018 (6.7%) vs 2014 (50%). Computed tomography was requested in 5/52 cases (9.6%) in 2014 and 8/70 cases (11.4%) in 2018, all cases involved an SS. Significantly more patients (14/52, 27%) were managed surgically in 2014 compared to 2018 (10/70, 14%). All patients were discharged with the exception of 1 patient in each group who required later surgical intervention. CONCLUSIONS: 1. The widely disseminated ProFHER trial is likely to have influenced contemporary clinical practice. 2. This study shows non-shoulder specialists are more likely to manage these patients conservatively and without the involvement of shoulder surgeons post ProFHER. 3. This impact on clinical outcomes requires further research.

Cannulated screw fixation for Garden I and II intracapsular hip fractures : five-year follow-up and posterior tilt analysis.

AIMS: In UK there are around 76,000 hip fractures occur each year 10% to 15% of which are undisplaced intracapsular. There is considerable debate whether internal fixation is the most appropriate treatment for undisplaced fractures in older patients. This study describes cannulated hip screws survivorship analysis for patients aged ≥ 60 years with undisplaced intra-capsular fractures. METHODS: This was a retrospective cohort study of consecutive patients aged ≥ 60 years who had cannulated screws fixation for Garden I and II fractures in a teaching hospital between March 2013 and March 2016. The primary outcome was further same-side hip surgery. Descriptive statistics were used and Kaplan-Meier estimates calculated for implant survival. RESULTS: A total of 114 operations were performed on 112 patients with a mean age of 80.2 years (SD 8.9). The 30-day and one-year mortality were 1% (n = 1) and 13% (n = 15), respectively. Median follow-up was 6.6 years (interquartile range 6.0 to 7.3). Kaplan-Meier estimates showed a survivorship of 95% at one year and 90% at five years (95% confidence interval 84% to 95%) for cannulated screws. Nine patients underwent further hip surgery: four revision to total hip arthroplasty, one revision to hemiarthroplasty, three removals of screws, and one haematoma washout. Posterior tilt was assessable in 106 patients; subsequent surgery was required in two of the six patients identified with a posterior angle > 20° (p = 0.035 vs angle < 20°). Of the 100 patients with angle < 20°, five-year survivorship was 91%, with seven patients requiring further surgery. CONCLUSION: This study of cannulated hip screw fixation for undisplaced fractures in patients aged ≥ 60 years reveals a construct survivorship without further operation of 90% at five years. Cannulated screws can be considered a safe reliable treatment option for Garden I and II fractures. Caution should be taken if posterior tilt angle on lateral view exceeds 20°, due to a higher failure rate and reoperation, and considered for similar management to Garden III and IV injuries. Cite this article: Bone Jt Open 2022;3(3):182-188.

A prebiotic diet modulates microglial states and motor deficits in α-synuclein overexpressing mice.

Parkinson's disease (PD) is a movement disorder characterized by neuroinflammation, α-synuclein pathology, and neurodegeneration. Most cases of PD are non-hereditary, suggesting a strong role for environmental factors, and it has been speculated that disease may originate in peripheral tissues such as the gastrointestinal (GI) tract before affecting the brain. The gut microbiome is altered in PD and may impact motor and GI symptoms as indicated by animal studies, although mechanisms of gut-brain interactions remain incompletely defined. Intestinal bacteria ferment dietary fibers into short-chain fatty acids, with fecal levels of these molecules differing between PD and healthy controls and in mouse models. Among other effects, dietary microbial metabolites can modulate activation of microglia, brain-resident immune cells implicated in PD. We therefore investigated whether a fiber-rich diet influences microglial function in α-synuclein overexpressing (ASO) mice, a preclinical model with PD-like symptoms and pathology. Feeding a prebiotic high-fiber diet attenuates motor deficits and reduces α-synuclein aggregation in the substantia nigra of mice. Concomitantly, the gut microbiome of ASO mice adopts a profile correlated with health upon prebiotic treatment, which also reduces microglial activation. Single-cell RNA-seq analysis of microglia from the substantia nigra and striatum uncovers increased pro-inflammatory signaling and reduced homeostatic responses in ASO mice compared to wild-type counterparts on standard diets. However, prebiotic feeding reverses pathogenic microglial states in ASO mice and promotes expansion of protective disease-associated macrophage (DAM) subsets of microglia. Notably, depletion of microglia using a CSF1R inhibitor eliminates the beneficial effects of prebiotics by restoring motor deficits to ASO mice despite feeding a prebiotic diet. These studies uncover a novel microglia-dependent interaction between diet and motor symptoms in mice, findings that may have implications for neuroinflammation and PD.

A Systematic Review of the Value of a Bladder Scan in Cauda Equina Syndrome Diagnosis.

Cauda equina syndrome (CES) is one of the emergency conditions that can lead to devastating permanent functional disabilities, if misdiagnosed. Multiple studies have questioned the reliability of clinical assessment in diagnosing CES, whether some of the features should be considered to be potential red flags. Bladder dysfunction can reflect CE compromise. The post-void residual (PVR) volume bladder scan is useful in CES diagnosis, but to date there has been no single systematic review supporting its use. Furthermore, there is no clear cut-off point to consider PVR statistically significant. The aim of the study is to perform a systematic review of the current evidence behind the use of the PVR bladder scan as a diagnostic tool for CES diagnosis. This was a comprehensive search using Medline, PubMed and Embase. All articles included post-void bladder scans with the mentioned clear cut-off volume as a diagnostic parameter. A total of five study articles from 1955 fit with our inclusion and exclusion criteria. The total number of patients who had a bladder scan was 531. CES was confirmed in 85 cases. Bladder scan diagnosed 70 cases and excluded 327. The best results for both sensitivity and specificity in correlation with the sample of the study were for PVR more than 200 ml. Measuring the post-void urine volume using a bladder scan is an essential tool in the diagnosis of CES. There is a significant correlation between the PVR volume more than 200 ml and higher sensitivity and specificity.

Stress and Anxiety Management During the COVID-19 Pandemic (Lessons Learnt from a Cohort of Orthopaedic Registrars Redeployed to ITU).

BACKGROUND: Working during the coronavirus pandemic has had a significant impact on health care workers. A group of orthopaedic trainees at Royal Gwent Hospital, UK, were redeployed to intensive therapy unit for four weeks during COVID-19 pandemic. This study reviews our experience; focusing on causes of stress and anxiety, and how they were managed. The lessons learnt could be used as a framework for pre-emptive me-asures during future challenges. MATERIAL AND METHODS: Orthopaedic registrars were divided into two groups. Seven trainees (Redeployed group) moved to ITU for four weeks to support the critical care team. The other group (Retained group) of eight registrars continued to cover orthopaedic rota. A survey was done for anxiety levels comparing the two groups at three time points during these four weeks. RESULTS: Anxiety and stress in the ITU-redeployed group was comparatively less than the continuing group as time progressed during the redeployment. CONCLUSIONS: 1. The disruptive impact of the COVID-19 pandemic has been a source of massive stress and an-xiety for health care workers. 2. Our experience shows that stress is controllable with the correct strategies. 3. The main points are early identification of vulnerable groups, proper induction, active involvement, adequate explanation, appreciation, good communication, and available psychological support whenever needed. 4. These are essential to maintain a resilient workforce against upcoming waves of COVID-19.

Trauma surgery at a designated COVID-19-free site during the pandemic: a safe model and a possible way to restart routine elective surgery.

AIMS: Elective operating was halted during the COVID-19 pandemic to increase the capacity to provide care to an unprecedented volume of critically unwell patients. During the pandemic, the orthopaedic department at the Aneurin Bevan University Health Board restructured the trauma service, relocating semi-urgent ambulatory trauma operating to the isolated clean elective centre (St. Woolos' Hospital) from the main hospital receiving COVID-19 patients (Royal Gwent Hospital). This study presents our experience of providing semi-urgent trauma care in a COVID-19-free surgical unit as a safe way to treat trauma patients during the pandemic and a potential model for restarting an elective orthopaedic service. METHODS: All patients undergoing surgery during the COVID-19 pandemic at the orthopaedic surgical unit (OSU) in St. Woolos' Hospital from 23 March 2020 to 24 April 2020 were included. All patients that were operated on had a telephone follow-up two weeks after surgery to assess if they had experienced COVID-19 symptoms or had been tested for COVID-19. The nature of admission, operative details, and patient demographics were obtained from the health board's electronic record. Staff were assessed for sickness, self-isolation, and COVID-19 status. RESULTS: A total of 58 surgical procedures were undertaken at the OSU during the study period; 93% (n = 54) of patients completed the telephone follow-up. Open reduction and internal fixation of ankle and wrist fractures were the most common procedures. None of the patients nor members of their households had developed symptoms suggestive of COVID-19 or required testing. No staff members reported sick days or were advised by occupational health to undergo viral testing. CONCLUSION: This study provides optimism that orthopaedic patients planned for surgery can be protected from COVID-19 nosocomial transmission at separate COVID-19-free sites.Cite this article: Bone Joint Open 2020;1-6:302-308.

The role of orthopaedic trainees during the COVID-19 pandemic and impact on post-graduate orthopaedic education: a four-nation survey of over 100 orthopaedic trainees.

AIMS: The COVID-19 pandemic has had a significant impact on the provision of orthopaedic care across the UK. During the pandemic orthopaedic specialist registrars were redeployed to "frontline" specialties occupying non-surgical roles. The impact of the COVID-19 pandemic on orthopaedic training in the UK is unknown. This paper sought to examine the role of orthopaedic trainees during the COVID-19 and the impact of COVID-19 pandemic on postgraduate orthopaedic education. METHODS: A 42-point questionnaire was designed, validated, and disseminated via e-mail and an instant-messaging platform. RESULTS: A total of 101 orthopaedic trainees, representing the four nations (Wales, England, Scotland, and Northern Ireland), completed the questionnaire. Overall, 23.1% (23/101) of trainees were redeployed to non-surgical roles. Of these, 73% (17/23) were redeployed to intensive treatment units (ITUs), 13% (3/23) to A/E, and 13%(3/23%) to general medicine. Of the trainees redeployed to ITU 100%, (17/17) received formal induction. Non-deployed or returning trainees had a significant reduction in sessions. In total, 42.9% (42/101) % of trainees were not timetabled into fracture clinic, 53% (53/101) of trainees had one allocated theatre list per week, and 63.8%(64/101) of trainees did not feel they obtained enough experience in the attached subspecialty and preferred repeating this. Overall, 93% (93/101) of respondents attended at least one weekly online webinar, with 79% (79/101) of trainees rating these as useful or very useful, while 95% (95/101) trainees attended online deanery teaching which was rated as more useful than online webinars (p = 0.005). CONCLUSION: Orthopaedic specialist trainees occupied an important role during the COVID-19 pandemic. COVID-19 has had a significant impact on orthopaedic training. It is imperative this is properly understood to ensure orthopaedic specialist trainees achieve competencies set out in the training curriculum.Cite this article: Bone Joint Open 2020;1-11:676-682.

Different degradation rates of nanofiber vascular grafts in small and large animal models.

Nanofiber vascular grafts have been shown to create neovessels made of autologous tissue, by in vivo scaffold biodegradation over time. However, many studies on graft materials and biodegradation have been conducted in vitro or in small animal models, instead of large animal models, which demonstrate different degradation profiles. In this study, we compared the degradation profiles of nanofiber vascular grafts in a rat model and a sheep model, while controlling for the type of graft material, the duration of implantation, fabrication method, type of circulation (arterial/venous), and type of surgery (interposition graft). We found that there was significantly less remaining scaffold (i.e., faster degradation) in nanofiber vascular grafts implanted in the sheep model compared with the rat model, in both the arterial and the venous circulations, at 6 months postimplantation. In addition, there was more extracellular matrix deposition, more elastin formation, more mature collagen, and no calcification in the sheep model compared with the rat model. In conclusion, studies comparing degradation of vascular grafts in large and small animal models remain limited. For clinical translation of nanofiber vascular grafts, it is important to understand these differences.

Bioprinting of freestanding vascular grafts and the regulatory considerations for additively manufactured vascular prostheses.

Vasculature is the network of blood vessels of an organ or body part that allow for the exchange of nutrients and waste to and from every cell, thus establishing a circulatory equilibrium. Vascular health is at risk from a variety of conditions that includes disease and trauma. In some cases, medical therapy can alleviate the impacts of the condition. Intervention is needed in other instances to restore the health of abnormal vasculature. The main approaches to treat vascular conditions are endovascular procedures and open vascular reconstruction that often requires a graft to accomplish. However, current vascular prostheses have limitations that include size mismatch with the native vessel, risk of immunogenicity from allografts and xenografts, and unavailability of autografts. In this review, we discuss efforts in bioprinting, an emerging method for vascular reconstruction. This includes an overview of 3D printing processes and materials, graft characterization strategies and the regulatory aspects to consider for the commercialization of 3D bioprinted vascular prostheses.

The use of platelet-rich fibrin in lumbar interbody fusion in lytic spondylolisthesis.

STUDY DESIGN: This was a retrospective observational study. AIM: The aim of this study was to evaluate the effectiveness of applying the platelet-rich fibrin (PRF) with bone graft in accelerating the rate of lumbar interbody fusion. SETTINGS AND DESIGN: This was a retrospective study measuring the outcome of posterior lumbar interbody fusion (PLIF) combined with PRF versus PLIF alone in the management of lytic spondylolisthesis. SUBJECTS AND METHODS: Forty patients were treated with instrumented PLIF for low-grade lytic spondylolisthesis and divided into two equal groups: one with addition of PRF to the bone graft and the other without. The minimum follow-up was 2 years. Clinical outcome was measured by the Oswestry Disability Index (ODI) and Visual Analogue Pain Scale (VAS) at 3, 6, and 12 months postoperatively. Radiological outcome was measured by standing X-ray at 3, 6, 12, and 24 months and computed tomography at 6 and 12 months postoperatively. RESULTS: ODI for the PRF group improved by 60% and 79% at 6 and 12 months, respectively, whereas for the non-PRF group, it improved by 55% and 70%. Radiological outcome showed fusion in 15 of 20 cases in the PRF group (75%) by the 6th month and in 19 of 20 cases (95%) by 1 year and 100% at 2 years. In the control group, fusion was present in 12 of 20 cases (60%) by the 6th month and in 13 of 20 cases in the PRF group (65%) by 1 year and 90% at 2 years (P < 0.05). CONCLUSIONS: These preliminary results show that PRF accelerates the rate of fusion in low-grade lytic spondylolisthesis in short-term follow-up.

The expandable transforaminal lumbar interbody fusion - Two years follow-up.

STUDY DESIGN: This was a retrospective, observational study. OBJECTIVES: We hypothesize that the expandable transforaminal lumbar interbody fusion (TLIF) cage achieves satisfactory clinical outcomes while allowing for safe placement, improvement, and maintenance of foraminal and disc dimensions at 24 months postsurgery with low risk of cage migration, subsidence, and nerve injury. METHODS: TLIF with expandable cages was performed in 54 patients (62 levels) over a 24-month-period using open midline or minimally invasive surgery techniques with placement of Globus Caliber, Rise, or Altera expandable cages. All patients underwent clinical and radiological assessment at 6 weeks, 6 months, 1, and 2 years postoperatively. Clinical outcome was measured by Oswestry disability index (ODI), visual analog pain score for both back and leg (visual analog scores [VASs]). Radiological assessment was done by X-ray standing lateral position. RESULTS: There were significant clinical improvements in ODI, VAS leg, and VAS back at all postoperative time points. Disc height, foraminal height, focal Cobb angle, and global Cobb angle were significantly increased and maintained at all time points for 24 months (P < 0.001). Dural tear occurred in one patient (1.9%). There were neither intra- or postoperative neurological complications nor cage subsidence nor migration. CONCLUSIONS: These preliminary results indicate that the use of an expandable interbody cage achieves good clinical outcomes by improving and maintaining foraminal dimensions and disc height with minimal complication rate.

Lumbar fusion for lytic spondylolisthesis: Is an interbody cage necessary?

STUDY DESIGN: This study was a retrospective observational study. PURPOSE: The purpose of the study was to determine the radiological and clinical outcome of using locally sourced autologous bone graft in the surgical management of single-level lumbar lytic spondylolisthesis. BACKGROUND: Many spinal surgeons supplement pedicle screw fixation of lumbar spondylolisthesis with cages. In developing countries, the high cost of interbody cages has precluded their use, with surgeons resorting to filling the interbody space with different types of bone graft instead. This study reports on the clinical and radiological outcome of posterior lumbar interbody fusions for low-grade lytic spondylolisthesis using locally sourced autologous bone graft. MATERIAL AND METHODS: Posterior interbody fusion was performed in 22 consecutive patients over 18-month period, using (BRAND) pedicle screw system and locally sourced bone graft, i.e., bone removed during neural decompression. There were no postoperative restrictions, and all patients underwent clinical outcome measurements using Oswestry Disability Index (ODI), visual analogue pain score (VAS) at a minimum follow-up of 12 months, and computed tomography (CT) assessment of fusion with intraobserver validation by radiology consultant blinded, at 6 and12 months. Nearly 50% of the population were smokers. RESULTS: There was significant clinical improvement in ODI, VAS back pain, and VAS leg pain (P < 0.001). By contrast, the radiologic fusion rate measured by CT at 12 months was less satisfactory at 64%. There was no difference in clinical outcome between the fused group and nonfused population. CONCLUSIONS: These results indicate that the use of locally sourced bone graft in single-level lumbar lytic low-grade spondylolisthesis. Interbody fusion provides good clinical outcomes. The use of an interbody cage may not be clinically necessary. Our radiologic outcome, however, shows inferior fusion rates compared with published data. Future research will focus on long-term outcomes.