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.

Moving orthopaedic procedures out of the operating theatre:Outpatient needle arthroscopy can reduce cost & waste, and increase inpatient capacity compared to conventional knee arthroscopy.

BACKGROUND: Needle arthroscopy (NA) is an emerging technique that could streamline pathways, facilitate timely care, and reduce service burden. The primary aim was to assess the practical and economic viability of an outpatient NA service. Secondary aims were to assess the relative costs and benefits compared to a conventional arthroscopy (CA) service. METHODS: This service feasibility study was conducted between 2021-2022 in a high-volume national treatment centre. A NA pathway was established for patients with chronic soft tissue pathology or early degenerative knee disease. The pathway was evaluated in terms of: i) cost; ii) efficiency, and iii) waste production, and an assessment was conducted of the patient-related and service-related effects. RESULTS: The cost of the NA pathway was £1555.20 per patient, compared to £2,351.53 for CA. Time to management was 45 days for NA versus 180 days for CA. The NA pathway involved two hospital attendances, whereas CA required a minimum of three. NA cases produced 1.4 kg of non-recyclable waste compared to 5.0 kg produced by CA. For every two cases managed by NA instead of CA, capacity for one additional obligate-inpatient procedure was created. CONCLUSIONS: The NA pathway offers a technically and economically viable approach for the management of refractory knee symptoms in the context of chronic soft tissue or early degenerative disease. NA placed less demand on hospital resources, produced two-thirds less non-recyclable waste, and is amenable to a one-stop clinic approach. Clinical studies focused on objective and patient-reported outcome measures are required to assess clinical efficacy.

Vitamin D Supplementation Is Associated with a Reduction in Self-Reported Falls among Older Adults with Previous Fall History - Feasibility Study.

BACKGROUND: Vitamin D insufficiency contributes to muscle weakness and a higher risk of falls in older adults. OBJECTIVES: This study explored the impact of vitamin D supplementation on self-reported falls and physical function in older adults with low vitamin D levels and a recent fall history. MATERIALS AND METHODS: Twenty-five older adults ≥ 70 years with two or more falls during the past year, low vitamin D blood levels (≥10 ng/ml and < 30 ng/mL), and slow gait speed (1.2 m/s) participated in a 6-month vitamin D supplementation (800 IU/day) study. A modified version of the Morse Fall Scale questionnaire was used to assess frequency of falls over one-year prior to study enrollment. Functional outcomes (short physical performance battery, handgrip strength, gait Timed Up and Go, and six-minute walk), and vitamin D levels were assessed at baseline and 6-month follow-up. RESULTS: Based on diaries and pill counts, participants were generally adherent to the intervention (6 of 7 days per week). Supplementation with 800 IU/day of vitamin D for 6 months increased blood vitamin D levels from 23.25±4.8 ng/ml to 29.13±6.9 ng/ml (p<0.001). Self-reported number of falls decreased from an average of 3.76 ± 2.2 falls in one-year to 0.76 plusmn; 1.4 falls (p <0.0001) over the 6-month intervention. No changes in functional outcome measures were observed. CONCLUSIONS: Vitamin D supplementation at the currently recommended dose of 800 IU/day increased blood vitamin D levels and reduced frequency of falls in older adults with low vitamin D levels and a recent fall history.

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 multi-disciplinary management of complex congenital and acquired tracheo-oesophageal fistulae.

AIM OF THE STUDY: Complex tracheo-oesophageal fistulae (TOF) are rare congenital or acquired conditions in children. We discuss here a multidisciplinary (MDT) approach adopted over the past 5 years. METHODS: We retrospectively collected data on all patients with recurrent or acquired TOF managed at a single institution. All cases were investigated with neck and thorax CT scan. Other investigations included flexible bronchoscopy and bronchogram (B&B), microlaryngobronchoscopy (MLB) and oesophagoscopy. All cases were subsequently discussed in an MDT meeting on an emergent basis if necessary. MAIN RESULTS: 14 patients were referred during this study period of which half had a congenital aetiology and the other half were acquired. The latter included button battery ingestions (5/7) and iatrogenic injuries during oesophageal atresia (OA) repair. Surgical repair was performed on cardiac bypass in 3/7 cases of recurrent congenital fistulae and all cases of acquired fistulae. Post-operatively, 9/14 (64%) patients suffered complications including anastomotic leak (1), bilateral vocal cord paresis (1), further recurrence (1), and mortality (1). Ten patients continue to receive surgical input encompassing tracheal/oesophageal stents and dilatations. CONCLUSIONS: MDT approach to complex cases is becoming increasingly common across all specialties and is important in making decisions in these difficult cases. The benefits include shared experience of rare cases and full access to multidisciplinary expertise.

Tissue-Engineered Tracheal Replacement in a Child: A 4-Year Follow-Up Study.

In 2010, a tissue-engineered trachea was transplanted into a 10-year-old child using a decellularized deceased donor trachea repopulated with the recipient's respiratory epithelium and mesenchymal stromal cells. We report the child's clinical progress, tracheal epithelialization and costs over the 4 years. A chronology of events was derived from clinical notes and costs determined using reference costs per procedure. Serial tracheoscopy images, lung function tests and anti-HLA blood samples were compared. Epithelial morphology and T cell, Ki67 and cleaved caspase 3 activity were examined. Computational fluid dynamic simulations determined flow, velocity and airway pressure drops. After the first year following transplantation, the number of interventions fell and the child is currently clinically well and continues in education. Endoscopy demonstrated a complete mucosal lining at 15 months, despite retention of a stent. Histocytology indicates a differentiated respiratory layer and no abnormal immune activity. Computational fluid dynamic analysis demonstrated increased velocity and pressure drops around a distal tracheal narrowing. Cross-sectional area analysis showed restriction of growth within an area of in-stent stenosis. This report demonstrates the long-term viability of a decellularized tissue-engineered trachea within a child. Further research is needed to develop bioengineered pediatric tracheal replacements with lower morbidity, better biomechanics and lower costs.

Radiation doses from fluoroscopically guided cardiac catheterization procedures in children and young adults in the United Kingdom: a multicentre study.

OBJECTIVE: To gather data on radiation doses from fluoroscopically guided cardiac catheterization procedures in patients aged under 22 years at multiple centres and over a prolonged period in the UK. To evaluate and explain variation in doses. To estimate patient-specific organ doses and allow for possible future epidemiological analysis of associated cancer risks. METHODS: Patient-specific data including kerma area product and screening times from 10,257 procedures carried out on 7726 patients at 3 UK hospitals from 1994 until 2013 were collected. Organ doses were estimated from these data using a dedicated dosimetry system based on Monte Carlo computer simulations. RESULTS: Radiation doses from these procedures have fallen significantly over the past two decades. The organs receiving the highest doses per procedure were the lungs (median across whole cohort, 20.5 mSv), heart (19.7 mSv) and breasts (13.1 mSv). Median cumulative doses, taking into account multiple procedures, were 23.2, 22.2 and 16.7 mSv for these organs, respectively. Bone marrow doses were relatively low (median per procedure, 3.2 mSv; cumulative, 3.6 mSv). CONCLUSION: Most modern cardiac catheterizations in children are moderately low-dose procedures. Technological advances appear to be the single most important factor in the fall in doses. Patients undergoing heart transplants undergo the most procedures. An epidemiological assessment of cancer risks following these procedures may be possible, especially using older data when doses were higher. ADVANCES IN KNOWLEDGE: This is the first large-scale, patient-specific assessment of organ doses from these procedures in a young population.

Measures of participation outcomes related to hand use for 2- to 12-year-old children with disabilities: a systematic review.

Many interventions have been used to improve children's hand-related impairments or hand skill performance in functional activities so as to promote life participation. There is thus a need to have suitable instruments assessing children's participation in life situations that specifically require hand use in order to support and evaluate such interventions. This systematic review investigated the availability of potential instruments that can be used to assess children's participation specifically in life situations requiring hand use. Clinical utility and evidence for psychometric properties were also sourced. Database searches initially identified measures that were used to evaluate participation of children aged 2-12 years, involved self- or proxy report or interview administration and had generic application for a range of disabilities/diagnoses. These measures were further evaluated to determine if they fulfilled the above inclusion criteria and contained at least 60% of the items involving hand use. Further searches for psychometric evidence were undertaken for the eligible measures. Fourteen measures were identified and nine met the inclusion criteria. However, none of these measures, except for the Children Helping Out: Responsibilities, Expectations, and Supports (CHORES), contained all items related to hand use. Most of the included measures had limited psychometric properties. Only the Children's Assessment of Participation and Enjoyment/Preferences for Activities of Children (CAPE/PAC), the School Function Assessment-Participation section (SFA-P) and the Children Participation Questionnaire (CPQ) revealed sufficient evidence of validity and reliability. The findings suggest a need for adapting existing participation measures or developing new ones that specifically assess participation in life situations requiring hand use to support interventions.

Bronchopleural fistula in a newborn undergoing ECMO-transbronchial closure.

Refractory pneumothoraces with bronchopleural fistula (BPF) pose a significant challenge in managing critically sick and ventilated neonates. We report a case of the term female neonate being treated with extracorporeal membrane oxygenation (ECMO) support for meconium aspiration and presumed sepsis, with a significant air leak refractory to pleural drainage that was managed using endobronchial application of cyanoacrylate (enbucrilate) glue to seal the leak.

Correlation of endogenous hormonal levels, fibroglandular tissue volume and percent density measured using 3D MRI during one menstrual cycle.

BACKGROUND: We measured breast density (BD) on MRI and correlated with endogenous hormonal levels. PATIENTS AND METHODS: Twenty-four premenopausal women received four weekly breast MRI. A blood sample was collected on the same day of MRI. BD was measured using a computer-based algorithm. The generalized estimation equation method was applied to model mean fibroglandular tissue volume (FV) and mean percent density (PD) from predictor variables including estradiol, progesterone, and week during a cycle. RESULTS: In week 3, a borderline significant correlation between estradiol and PD (r = 0.43, P = 0.04), estradiol and FV (r = 0.40, P = 0.05) and between progesterone and FV (r = 0.42, P = 0.04) was noted. The FV and PD measured in weeks 4 and 1 were higher than in weeks 2 and 3, adjusted for variation in endogenous estradiol and progesterone, indicating that the hormone change could not account for the changes in density. No lag effect of endogenous hormone on the change of FV or PD was noted (all P-values > 0.05). CONCLUSIONS: Our results showed that BD is not strongly associated with the endogenous hormone. Their association with breast cancer risk was likely coming from different mechanisms, and they should be considered as independent risk factors.

Role of dietary polyamines in a phase III clinical trial of difluoromethylornithine (DFMO) and sulindac for prevention of sporadic colorectal adenomas.

BACKGROUND: The polyamine-inhibitory regimen difluoromethylornithine (DFMO)+sulindac has marked efficacy in preventing metachronous colorectal adenomas. Polyamines are synthesised endogenously and obtained from dietary sources. Here we investigate dietary polyamine intake and outcomes in the DFMO+sulindac colorectal adenoma prevention trial. METHODS: Dietary polyamine data were available for 188 of 267 patients completing the study. Total dietary polyamine content was derived by the sum of dietary putrescine, spermine and spermidine values and categorised into two groups: highest (>75-100%) vs the lower three quartiles (0-25, 25-50 and 50-75%). Baseline tissue polyamine concentration and ODC1 genotype were determined. Logistic regression models were used for risk estimation. RESULTS: A significant interaction was detected between dietary polyamine group and treatment with regard to adenoma recurrence (P=0.012). Significant metachronous adenoma risk reduction was observed after DFMO+sulindac treatment in dietary polyamine quartiles 1-3 (risk ratio (RR) 0.19; 95% confidence interval (CI) 0.08-0.42; P<0.0001) but not in quartile 4 (RR 1.51; 95% CI 0.53-4.29; P=0.44). However, a lower number of events in the placebo group within dietary quartile 4 confound the aforementioned risk estimates. CONCLUSION: These preliminary findings reveal complex relationships between diet and therapeutic prevention, and they support further clinical trial-based investigations where the dietary intervention itself is controlled.

Bronchomegaly as a complication of fetal endoscopic tracheal occlusion. A caution and a possible solution.

Fetal medicine is developing rapidly and aims to improve the outcome for fetuses with congenital anomalies. Fetal endoscopic tracheal occlusion (FETO) has been developed for fetuses with congenital diaphragmatic hernia to counterbalance the compression of the lung by the abdominal viscera, preserving the pulmonary maturation. Because the perinatal morbidity and mortality of patients treated with FETO have decreased, new complications are emerging in the older survivors. Tracheomegaly has been reported to be a late complication of FETO, sometimes requiring tracheostomy. We report a case of bronchial dilatation after FETO and suggest an alternative surgical treatment.

Serial serum ferritin measurements in untreated HFE C282Y homozygotes in the Hemochromatosis and Iron Overload Screening Study.

Hemochromatosis has often been associated with progressive iron overload, but the natural history of iron accumulation in untreated C282Y homozygotes has been reported infrequently. The Hemochromatosis and Iron Overload Screening (HEIRS) Study screened 101 168 primary care participants for iron overload using transferrin saturation, unbound iron-binding capacity, Serum ferritin (SF), and HFE C282Y and H63D genotyping. SF was measured at initial screening (IS) and again when selected participants returned for a clinical examination (CE). The change in SF over the observation period (defined as ferritin rate of change) was analyzed according to age, gender, initial SF, initial SF/age, transferrin saturation, and iron removed by phlebotomy in C282Y homozygotes. Seventy-four male and 133 female untreated C282Y homozygotes were observed over a median of 112 days (34-924 days) between IS and CE. In men, SF increased in 54% and decreased in 46%. In women, SF increased in 50% and decreased in 50%. The significant variables affecting the SF rate were initial log SF (P = 0.0027) and transferrin saturation (P < 0.0001). Male C282Y homozygotes with higher SF rates (n = 27, upper 50th percentile) had significantly greater iron removed by phlebotomy (mean 4.93 g, range 1.0-17 g) than those with lower SF rates (n = 26, lower 50th percentile) (mean 2.6 g, 0.42-7.1, P < 0.05). SF was as likely to decrease as increase in untreated C282Y homozygotes over this relatively brief observation period. Incremental increases in SF are not inevitable in untreated C282Y homozygotes.

Patellar resurfacing versus no resurfacing in Scorpio total knee arthroplasty.

This retrospective study compared the results of patellar resurfacing versus no resurfacing in 121 patients (142 knees) who underwent Scorpio total knee arthroplasty (TKA) between January 2002 and September 2004. Mean follow-up was 33 months in the nonresurfaced group and 18 months in the resurfaced group. The 2 groups were similar in age and gender. The incidence of anterior knee pain was 25% in the nonresurfaced group compared to 7% in the resurfaced group (P = 0.05), and the rate of revision was 10% in the nonresurfaced group compared to zero in the resurfaced group (P = 0.013). Mean Euroquol score was 91 in the nonresurfaced group compared to 95 in the resurfaced group (P = 0.26). Euroquol score, Knee Society score, knee instability, return to preoperative functional level, ability to kneel, use of a walking aid, and presence of limp were not significantly different between the 2 groups. The results of this study suggest a more consistent outcome can be achieved with patellar resurfacing in TKA with the Scorpio prosthesis.

A genome-wide linkage scan for iron phenotype quantitative trait loci: the HEIRS Family Study.

Iron overload phenotypes in persons with and without hemochromatosis are variable. To investigate this further, probands with hemochromatosis or evidence of elevated iron stores and their family members were recruited for a genome-wide linkage scan to identify potential quantitative trait loci (QTL) that contribute to variation in transferrin saturation (TS), unsaturated iron-binding capacity (UIBC), and serum ferritin (SF). Genotyping utilized 402 microsatellite markers with average spacing of 9 cM. A total of 943 individuals, 64% Caucasian, were evaluated from 174 families. After adjusting for age, gender, and race/ethnicity, there was evidence for linkage of UIBC to chromosome 4q logarithm of the odds (LOD) = 2.08, p = 0.001) and of UIBC (LOD = 9.52), TS (LOD = 4.78), and SF (LOD = 2.75) to the chromosome 6p region containing HFE (each p < 0.0001). After adjustments for HFE genotype and other covariates, there was evidence of linkage of SF to chromosome 16p (LOD = 2.63, p = 0.0007) and of UIBC to chromosome 5q (LOD = 2.12, p = 0.002) and to chromosome 17q (LOD = 2.19, p = 0.002). We conclude that these regions should be considered for fine mapping studies to identify QTL that contribute to variation in SF and UIBC.

Aspiration in the context of upper gastrointestinal endoscopy.

BACKGROUND: Pulmonary aspiration is a life-threatening complication of upper gastrointestinal endoscopy, the incidence of which has not been determined. Endoscopy-related aspiration has not been studied in procedures in which patients swallow a radiolabelled potential aspirate immediately before endoscopy and undergo nuclear scanning postprocedure. METHODS: A pilot study was conducted in which 200 MBq of nonabsorbable technetium-99m phytate in 10 mL of water was administered orally to 50 patients who were about to undergo endoscopy. Gamma camera images were obtained to ensure that there had been no aspiration before endoscopy. After endoscopy, a repeat scan was performed. Fluid aspirated through the endoscope was also collected and analyzed for radioactivity using a hand-held radiation monitor. RESULTS: No evidence of pulmonary aspiration was found in any of the patients studied. The mean estimated percentage of the initially administered radioactivity aspirated through the endoscope was 2.66% (range 0% to 10.3%). CONCLUSION: The present pilot study confirms earlier observations that clinically significant aspiration in the context of upper gastrointestinal endoscopy is uncommon. The incidence of aspiration may, however, be different in acutely bleeding patients undergoing endoscopy. For logistic reasons, this group could not be studied.

An evaluation of two indirect methods of estimating body weight in Holstein calves and heifers.

Monitoring the growth of replacement heifers is a useful management tool to assist producers in achieving a reasonable goal for age at first calving. Standard growth curves have been established, and heart girth tapes are widely available to estimate body weight (BW). Probably the easiest, and undoubtedly the most accurate, means of determining the actual BW of heifers is by using a calibrated electronic scale. However, if an electronic scale is not available, indirect methods of BW estimation are required. The hipometer is a new indirect tool that uses the external width between the greater trochanters of the left and right femurs to estimate BW. The purpose of this observational study was to evaluate the hipometer and the heart girth tape to estimate the BW of Holstein heifers, as compared with their actual weight recorded by an electronic scale. A total of 311 Holstein heifers in 4 research herds, ranging in age from 1 wk old to immediately prior to calving (24 mo), were used in this comparison. The mean BW of all heifers was 261 +/- 124 kg. The Pearson values of the correlation between the scale and hipometer weights, and the scale and tape weights were 0.92 and 0.94, respectively. The concordance correlations of scale weight with hipometer and tape weights were 0.98 and 0.99, respectively. The agreement among the 3 methods, as assessed by the kappa statistic, was substantial for heifers aged 3 to 15 mo. However, poor to no agreement was observed in heifers younger than 3 mo, as well as at 15 mo of age or greater (kappa 0 to 0.18). This is of particular concern because these groups represent the age when dairy heifers would be weaned (< 3 mo) and the age when breeding would normally commence (> 15 mo). We concluded that the hipometer is an easy and useful alternative method of estimating the BW of Holstein heifers, particularly in heifers aged 3 to 15 mo.