Genicular Artery embolisation in Patients with Osteoarthritis of the Knee (GENESIS) Using Permanent Microspheres: Long-Term Results.

PURPOSE: To report the 2-year follow-up of patients with mild-to-moderate knee osteoarthritis (OA) treated with genicular artery embolisation (GAE) as part of the GENESIS study. MATERIALS AND METHODS: Forty-six patients, median age = 60 (45-83) underwent GAE using permanent microspheres (100-300 µm). Technical success was defined as embolisation of the targeted genicular arteries. Knee Injury and Osteoarthritis Outcome Score (KOOS) and Visual Analogue Scale (VAS) (0-100 mm) were recorded at baseline, 6 weeks, 3 months, 1, 2 years. Contrast-enhanced MRI knee scans were acquired at baseline and 1 year, and evaluated with the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Functional MRI brain imaging and psychometric assessments were undertaken to investigate correlation between neuropsychological phenotypes and clinical outcome. Adverse events were recorded prospectively. RESULTS: Technical success was achieved in forty patients (87%). Mean VAS improved from 58.63 (SD = 20.57, 95% CI 52.7-65.5) at baselines to 37.7 at 2-years (SD = 26.3, 95% CI 27.0-47.5). Whole and subgroup KOOS were significantly improved at each timepoint with associated reductions in analgesia usage. WORMS analysis demonstrated significant reduction in synovitis (p < 0.05) with no cases of osteonecrosis. Self-limiting skin discolouration occurred in four patients. A self-limiting groin haematoma and single case of deep-vein thrombosis due to immobilisation were also recorded. Nine patients subsequently underwent knee arthroplasty with no additional operational complexities identified. Neuropsychometric assessment elucidated a correlation between baseline catastrophising and greater reduction in pain post GAE. CONCLUSION: GAE is a safe intervention for mild-moderate knee osteoarthritis, with sustained efficacy at 2 years. These results are promising and justify ongoing controlled trials.

Operative and non-operative management for intestinal emergencies: findings from a single-centre retrospective cohort study.

BACKGROUND: Patients with an intestinal emergency who do not have surgery are poorly characterised. This study used electronic healthcare records to provide a rapid insight into the number of patients admitted with an intestinal emergency and compare short-term outcomes for non-operative and operative management. METHODS: A single-centre retrospective cohort study was conducted at a tertiary NHS hospital (from 1 December 2013 to 31 January 2020). Patients were identified using diagnosis codes for intestinal emergencies, based on the inclusion criteria for the National Emergency Laparotomy Audit. Relevant data were extracted from electronic healthcare records (n=3,997). RESULTS: Nearly half of patients admitted with an intestinal emergency received nonoperative management (43.7%). Of those who underwent surgery, 63.7% were started laparoscopically. The non-operative group had a shorter hospital stay (median: 5.4 days vs 8.2 days [started laparoscopically] or 16.8 days [started open]) and fewer unintended intensive care admissions than the surgical group (2.4% vs 8.7% [started laparoscopically] 21.1% [started open]). However, 30-day mortality for non-operative treatment was double that for surgery (22.4% vs 10.1%). The 30-day mortality rate was found to be even higher for non-operative management (50.3%) compared with surgery (19.5%) in a sub-analysis of patients with admission National Early Warning Score ≥4 (n=683). CONCLUSION: The proportion of patients with intestinal emergencies who do not have surgery is greater than expected, and it appears that many respond well to non-operative treatment. However, 30-day mortality for non-operative management was high, and the low number of admissions to intensive care suggests that major invasive treatment was not appropriate for most in this group.

The effect of a novel, digital physical activity and emotional well-being intervention on health-related quality of life in people with chronic kidney disease: trial design and baseline data from a multicentre prospective, wait-list randomised controlled trial (kidney BEAM).

BACKGROUND: Physical activity and emotional self-management has the potential to enhance health-related quality of life (HRQoL), but few people with chronic kidney disease (CKD) have access to resources and support. The Kidney BEAM trial aims to evaluate whether an evidence-based physical activity and emotional wellbeing self-management programme (Kidney BEAM) leads to improvements in HRQoL in people with CKD. METHODS: This was a prospective, multicentre, randomised waitlist-controlled trial, with health economic analysis and nested qualitative studies. In total, three hundred and four adults with established CKD were recruited from 11 UK kidney units. Participants were randomly assigned to the intervention (Kidney BEAM) or a wait list control group (1:1). The primary outcome was the between-group difference in Kidney Disease Quality of Life (KDQoL) mental component summary score (MCS) at 12 weeks. Secondary outcomes included the KDQoL physical component summary score, kidney-specific scores, fatigue, life participation, depression and anxiety, physical function, clinical chemistry, healthcare utilisation and harms. All outcomes were measured at baseline and 12 weeks, with long-term HRQoL and adherence also collected at six months follow-up. A nested qualitative study explored experience and impact of using Kidney BEAM. RESULTS: 340 participants were randomised to Kidney BEAM (n = 173) and waiting list (n = 167) groups. There were 96 (55%) and 89 (53%) males in the intervention and waiting list groups respectively, and the mean (SD) age was 53 (14) years in both groups. Ethnicity, body mass, CKD stage, and history of diabetes and hypertension were comparable across groups. The mean (SD) of the MCS was similar in both groups, 44.7 (10.8) and 45.9 (10.6) in the intervention and waiting list groups respectively. CONCLUSION: Results from this trial will establish whether the Kidney BEAM self management programme is a cost-effective method of enhancing mental and physical wellbeing of people with CKD. TRIAL REGISTRATION: NCT04872933. Registered 5th May 2021.

Novel predictors of mortality in emergency bowel surgery: a single-centre cohort study.

Pre-operative risk stratification is a key part of the care pathway for emergency bowel surgery, as it facilitates the identification of high-risk patients. Several novel risk scores have recently been published that are designed to identify patients who are frail or significantly unwell. They can also be calculated pre-operatively from routinely collected clinical data. This study aimed to investigate the ability of these scores to predict 30-day mortality after emergency bowel surgery. A single centre cohort study was performed using our local data from the National Emergency Laparotomy Audit database. Further data were extracted from electronic hospital records (n = 1508). The National Early Warning Score, Laboratory Decision Tree Early Warning Score and Hospital Frailty Risk Score were then calculated. The most abnormal National or Laboratory Decision Tree Early Warning Score in the 24 or 72 h before surgery was used in analysis. Individual scores were reasonable predictors of mortality (c-statistic 0.699-0.740) but all were poorly calibrated. A National Early Warning Score ≥ 4 was associated with a high overall mortality rate (> 10%). A logistic regression model was developed using age, National Early Warning Score, Laboratory Decision Tree Early Warning Score and Hospital Frailty Risk Score as predictor variables, and its performance compared with other established risk models. The model demonstrated good discrimination and calibration (c-statistic 0.827) but was marginally outperformed by the National Emergency Laparotomy Audit score (c-statistic 0.861). All other models compared performed less well (c-statistics 0.734-0.808). Pre-operative patient vital signs, blood tests and markers of frailty can be used to accurately predict the risk of 30-day mortality after emergency bowel surgery.

Assessment of glaucoma awareness, uptake, and satisfaction with a free, targeted glaucoma screening program Southwest in Nigeria.

Background: Glaucoma is a global public eye health concern, being the number one cause of irreversible blindness. Aim: It is commoner, has an earlier onset, and is more aggressive in people of African descent. Awareness creation and screening activities have been identified as key components of the glaucoma care pathway. Subjects and Methods: This was a cross-sectional, descriptive study with analysis. The screening took place at the eye clinic, University College Hospital, Ibadan. Participants comprised all consenting adults aged 40 years and above who presented following a prescheduled telephone appointment during the 2021 World Glaucoma Week (WGW) activities. The main outcome variables were the awareness of glaucoma, and the uptake of and satisfaction with the free screening program. The associations between participants' prior awareness of glaucoma and their socio-demographic and clinical features were explored using the Chi-squared test. A P value of <0.05 was considered significant. Results: A total of 94 (47%) participants presented for the screening out of the 200 people who scheduled an appointment through the telephone appointment booking system. Forty-nine (52.1%) were males, and the mean (SD) age of participants was 55 years (10.9) with a range of 40-80 years. Fifty-eight (61.7%) participants had heard of glaucoma before the 2021 WGW awareness programs and 75.9% (44) gained some new knowledge from the programs. Newly diagnosed glaucoma was 9.6% (n = 9) of which seven (77.8%) had advanced glaucoma (CDR ≥0.9) in at least one eye. One hundred percent of the participants reported that they would recommend the screening to others. Conclusion: Targeted eye screening can help with the early detection of glaucoma. Patient satisfaction should be at the fore of eye health services to improve uptake.

Genicular artEry embolizatioN in patiEnts with oSteoarthrItiS of the Knee (GENESIS) Using Permanent Microspheres: Interim Analysis.

PURPOSE: Planned interim analysis of GENESIS; a prospective pilot study investigating the role of genicular artery embolization (GAE) in patients with mild to moderate osteoarthritis of the knee using permanent microspheres. METHODS: Thirty-eight patients, median age = 60 (45-83), attended for GAE using 100-300 µm permanent microspheres. All patients had mild to moderate knee OA, resistant to conservative treatments over 6 months. Knee MRI was performed at baseline, and 12 months, enabling semi-quantitative analysis using Whole-Organ Magnetic Resonance Imaging Score (WORMS). Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS) (0-100 mm) were completed at baseline, 6 weeks, 3 months (n = 32), and 1-year (n = 16). Adverse events were recorded prospectively. RESULTS: Technical success of accessing and embolizing the target genicular arteries was 84%. Six patients were not embolized: four due to a presumed risk of non-target embolization, and two due to a lack of hyperaemic target. Mean VAS improved from 60 (SD = 20, 95% CI 53-66) at baseline to 36 (SD = 24, 95% CI 28-44) at 3 months (p < 0.001) and 45 (SD = 30, 95% CI 30-60) at 1-year (p < 0.05). All KOOS subscales showed a significant improvement at 6-weeks, 3-months, and 1-year follow-up, except function in daily living, which reached borderline significance (p = 0.06) at 1-year. Four patients experienced mild self-limiting skin discoloration over the embolized territory. One patient experienced a small self-limiting groin haematoma. WORMS scores at 1-year follow-up showed significant improvement in synovitis (p < 0.05). There were no cases of osteonecrosis. CONCLUSION: GAE using permanent microspheres in patients with mild to moderate knee OA is safe, with potential efficacy at early follow-up.

The T-cell leukemia-associated ribosomal RPL10 R98S mutation enhances JAK-STAT signaling.

Several somatic ribosome defects have recently been discovered in cancer, yet their oncogenic mechanisms remain poorly understood. Here we investigated the pathogenic role of the recurrent R98S mutation in ribosomal protein L10 (RPL10 R98S) found in T-cell acute lymphoblastic leukemia (T-ALL). The JAK-STAT signaling pathway is a critical controller of cellular proliferation and survival. A proteome screen revealed overexpression of several Jak-Stat signaling proteins in engineered RPL10 R98S mouse lymphoid cells, which we confirmed in hematopoietic cells from transgenic Rpl10 R98S mice and T-ALL xenograft samples. RPL10 R98S expressing cells displayed JAK-STAT pathway hyper-activation upon cytokine stimulation, as well as increased sensitivity to clinically used JAK-STAT inhibitors like pimozide. A mutually exclusive mutation pattern between RPL10 R98S and JAK-STAT mutations in T-ALL patients further suggests that RPL10 R98S functionally mimics JAK-STAT activation. Mechanistically, besides transcriptional changes, RPL10 R98S caused reduction of apparent programmed ribosomal frameshifting at several ribosomal frameshift signals in mouse and human Jak-Stat genes, as well as decreased Jak1 degradation. Of further medical interest, RPL10 R98S cells showed reduced proteasome activity and enhanced sensitivity to clinical proteasome inhibitors. Collectively, we describe modulation of the JAK-STAT cascade as a novel cancer-promoting activity of a ribosomal mutation, and expand the relevance of this cascade in leukemia.

A portable magneto-optical trap with prospects for atom interferometry in civil engineering.

The high precision and scalable technology offered by atom interferometry has the opportunity to profoundly affect gravity surveys, enabling the detection of features of either smaller size or greater depth. While such systems are already starting to enter into the commercial market, significant reductions are required in order to reach the size, weight and power of conventional devices. In this article, the potential for atom interferometry based gravimetry is assessed, suggesting that the key opportunity resides within the development of gravity gradiometry sensors to enable drastic improvements in measurement time. To push forward in realizing more compact systems, techniques have been pursued to realize a highly portable magneto-optical trap system, which represents the core package of an atom interferometry system. This can create clouds of 107 atoms within a system package of 20 l and 10 kg, consuming 80 W of power.This article is part of the themed issue 'Quantum technology for the 21st century'.

Comparison of the National Early Warning Score in non-elective medical and surgical patients.

BACKGROUND: The National Early Warning Score (NEWS) is used to identify deteriorating patients in hospital. NEWS is a better discriminator of outcomes than other early warning scores in acute medical admissions, but it has not been evaluated in a surgical population. The study aims were to evaluate the ability of NEWS to discriminate cardiac arrest, death and unanticipated ICU admission in patients admitted to surgical specialties, and to compare the performance of NEWS in admissions to medical and surgical specialties. METHODS: Hospitalwide data over 31 months, from adult inpatients who stayed at least one night or died on the day of admission, were analysed. The data were categorized as elective or non-elective surgical or medical admissions. The ability of NEWS to discriminate the outcomes above in these different groups was assessed using the area under the receiver operating characteristic curve (AUROC). RESULTS: There were too few outcomes to permit meaningful comparison of elective admissions, so the analysis was constrained to comparison of non-elective admissions. NEWS performed equally well, or better, for surgical as for medical patients. For death within 24 h the AUROC for surgical admissions was 0·914 (95 per cent c.i. 0·907 to 0·922), compared with 0·902 (0·898 to 0·905) for medical admissions. For the combined outcome of any of death, cardiac arrest or unanticipated ICU admission, the AUROC was 0·874 (0·868 to 0·880) for surgical admissions and 0·874 (0·871 to 0·877) for medical admissions. CONCLUSION: NEWS discriminated deterioration in non-elective surgical patients at least as well as in non-elective medical patients.

Cryo-Electron Tomography and Subtomogram Averaging.

Cryo-electron tomography (cryo-ET) allows 3D volumes to be reconstructed from a set of 2D projection images of a tilted biological sample. It allows densities to be resolved in 3D that would otherwise overlap in 2D projection images. Cryo-ET can be applied to resolve structural features in complex native environments, such as within the cell. Analogous to single-particle reconstruction in cryo-electron microscopy, structures present in multiple copies within tomograms can be extracted, aligned, and averaged, thus increasing the signal-to-noise ratio and resolution. This reconstruction approach, termed subtomogram averaging, can be used to determine protein structures in situ. It can also be applied to facilitate more conventional 2D image analysis approaches. In this chapter, we provide an introduction to cryo-ET and subtomogram averaging. We describe the overall workflow, including tomographic data collection, preprocessing, tomogram reconstruction, subtomogram alignment and averaging, classification, and postprocessing. We consider theoretical issues and practical considerations for each step in the workflow, along with descriptions of recent methodological advances and remaining limitations.

Technical and Clinical Outcomes Following Colonic Stenting: A Seven-Year Analysis of 268 Procedures.

AIMS: To assess the factors contributing to the technical and clinical success of colorectal stenting for large bowel obstruction. METHODOLOGY: 268 cases of colonic stenting for large bowel obstruction were performed in 249 patients of mean age of 72 years (28-98) between 2006 and 2013. The majority of strictures were due to malignant disease, 244/268 (91 %). Diverticular strictures accounted for 24/268 (9 %). RESULTS: Overall technical success rate was 81 % (217/268), with a clinical success rate of 65 % (174/268). Duration of symptoms ranged from 0 to 180 days (mean 8 days). Technical success rate was seen to decrease with increasing symptom duration. For symptom duration of less than 1 week, technical success was 85.4 % (181/212) versus 69.6 % (39/56) for those with symptoms of greater than a week (p < 0.05). Clinical success rates fell from 71.3 % (107/150) to 59.3 % (70/118) (p < 0.05) when attempting to stent lesions of greater than 5 cm. There was also a significant reduction in clinical success when stenting lesions on a bend rather than a straight segment of colon 75.7 % (109/144) versus 59.7 % (74/124) (p < 0.05). A total of 20 (7.46 %) perforations were identified during the study. Stent migration occurred in 6.6 % of cases. In-stent stenosis occurred in 3.3 %. The overall 30-day all cause mortality rate was 9 %. CONCLUSION: Lesion size, location and duration of obstructive symptoms are statistically significant determinants of patient outcome. These factors could be used to advise patient selection for colonic stenting or direct progression to surgical intervention.

VESICULAR TRANSPORT. A structure of the COPI coat and the role of coat proteins in membrane vesicle assembly.

Transport of material within cells is mediated by trafficking vesicles that bud from one cellular compartment and fuse with another. Formation of a trafficking vesicle is driven by membrane coats that localize cargo and polymerize into cages to bend the membrane. Although extensive structural information is available for components of these coats, the heterogeneity of trafficking vesicles has prevented an understanding of how complete membrane coats assemble on the membrane. We combined cryo-electron tomography, subtomogram averaging, and cross-linking mass spectrometry to derive a complete model of the assembled coat protein complex I (COPI) coat involved in traffic between the Golgi and the endoplasmic reticulum. The highly interconnected COPI coat structure contradicted the current "adaptor-and-cage" understanding of coated vesicle formation.

Radiology and mesenteric ischaemia.

This review focuses on the radiology of mesenteric ischaemia. Covering the acute and chronic presentations, both of which result from impaired vascularisation of the gastrointestinal tract, we evaluate the role of radiographs, ultrasound, CT, MRI, and catheter angiography in the diagnosis of these conditions. Looking to the future, we also assess some of the emerging imaging techniques. Across medicine and surgery there has been a significant shift towards minimally invasive interventions. Although percutaneous revascularisation of chronic mesenteric ischaemia has been performed for some time, there has been a developing trend for the use of such techniques in acute mesenteric ischaemia. We evaluate the available evidence for the use of these percutaneous interventions and assess how they compare with or in some instances compliment traditional surgical alternatives.

Antibiotics in interventional radiology.

The range and number of interventional procedures is rapidly increasing each year. A major complication associated with many procedures is infection, which can result in serious adverse outcomes for the patient. Consequently, antibiotics are amongst the most common pharmaceuticals used by the interventionist, particularly for non-vascular procedures, yet almost no randomized controlled trial data exist to inform our decision when formulating appropriate antibiotic prophylaxis regimens. The purpose of this review is to provide an update on the utilization of antibiotics for common interventional radiology procedures, focusing on timing and duration of antibiotic prophylaxis.

Suspected iatrogenic ureteric injury: an approach to diagnostic imaging.

Iatrogenic ureteric injury (IUI) is the leading cause of ureteric trauma and a complication of major abdominal and pelvic surgery. IUI carries significant morbidity and mortality, which can be further compounded by delayed diagnosis due to its non-specific clinical presentation. We review ureteric anatomy, types of IUI, and imaging strategies available for diagnosis. We propose an imaging protocol for prompt diagnosis and follow-up.

The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing.

Schizophrenia (SZ) is a complex disease characterized by impaired neuronal functioning. Although defective alternative splicing has been linked to SZ, the molecular mechanisms responsible are unknown. Additionally, there is limited understanding of the early transcriptomic responses to neuronal activation. Here, we profile these transcriptomic responses and show that long non-coding RNAs (lncRNAs) are dynamically regulated by neuronal activation, including acute downregulation of the lncRNA Gomafu, previously implicated in brain and retinal development. Moreover, we demonstrate that Gomafu binds directly to the splicing factors QKI and SRSF1 (serine/arginine-rich splicing factor 1) and dysregulation of Gomafu leads to alternative splicing patterns that resemble those observed in SZ for the archetypal SZ-associated genes DISC1 and ERBB4. Finally, we show that Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in SZ. These results functionally link activity-regulated lncRNAs and alternative splicing in neuronal function and suggest that their dysregulation may contribute to neurological disorders.

Percutaneous cholecystostomy: the radiologist's role in treating acute cholecystitis.

Acute cholecystitis is a common condition, with laparoscopic cholecystectomy considered the gold-standard for surgical management. However, surgical options are often unfavourable in patients who are very unwell, or have numerous medical co-morbidities, in which the mortality rates are significant. Percutaneous cholecystostomy (PC) is an image-guided intervention, used to decompress the gallbladder, reducing patient's symptoms and the systemic inflammatory response. PC has been shown to be beneficial in high-risk patient groups, predominantly as a bridging therapy; allowing safer elective cholecystectomy once the patient has recovered from the acute illness; or, in the minority, as a definitive treatment in patients deemed unfit for surgery. This review aims to develop a broader understanding of PC, discussing its specific indications, patient management, technical factors, imaging guidance, and outcomes following the procedure.