Genicular Artery Embolisation in Patients with Osteoarthritis of the Knee (GENESIS 2): Protocol for a Double-Blind Randomised Sham-Controlled Trial.

Knee osteoarthritis is a leading cause of chronic disability and economic burden. In many patients who are not surgical candidates, existing treatment options are insufficient. Clinical evidence for a new treatment approach, genicular artery embolisation (GAE), is currently limited to single arm cohort, or small population randomised studies. This trial will investigate the use of a permanent embolic agent for embolisation of abnormal genicular arterial vasculature to reduce pain in patients with mild to moderate knee osteoarthritis. Up to 110 participants, 45 years or older, with knee pain for ≥ 3 months resistant to conservative treatment will be randomised (1:1) to GAE or a sham procedure. The treatment group will receive embolisation using 100-micron Embozene™ microspheres (Varian, a Siemens Healthineers Company) (investigational use for this indication in the UK), and the sham group will receive 0.9% saline in an otherwise identical procedure. Patients will be followed for 24 months. At 6 months, sham participants will be offered crossover to GAE. The primary endpoint is change of 4 Knee Injury and OA Outcome Score subscales (KOOS4) at 6 months post-randomisation. The study will also evaluate quality of life, health economics, imaging findings, and psychosocial pain outcomes. The primary manuscript will be submitted for publication after all participants complete 6 months of follow-up. The trial is expected to run for 3.5 years. Trial Registration: ClinicalTrials.gov, Identifier: NCT05423587.

Transcatheter embolisation in chronic musculoskeletal disorders.

Chronic musculoskeletal conditions affect millions of patients worldwide resulting in disability, reduced quality of life, and have a profound economic impact on the individual and society. Current treatment strategies fail patients who have not responded to conservative management but are not surgical candidates. Over the last decade, transcatheter embolisation has emerged as a potential treatment for these difficult to treat patients. By exploiting pathological neovascularisation within conditions such as knee osteoarthritis, adhesive capsulitis, and tendinopathy, embolisation has been used to improve patients' pain and function. This review explores the rationale for musculoskeletal transcatheter embolisation, illustrating the technique, and latest evidence for the most common procedures.

Genicular Artery Embolization Data Review.

Osteoarthritis of the knee poses an ever-expanding healthcare challenge worldwide. Current treatments include conservative methods such as weight loss, pharmacological treatments including NSAIDs, and surgical techniques including total knee arthroplasty. Although frequently successful, contraindications and failure of pharmacological agents leave many, especially with mild-moderate disease, without effective treatment. Genicular artery embolization is an interventional radiology technique being developed to fill this treatment gap. For this procedure to become established, the literature must provide evidence of its underlying scientific principles, safety, efficacy and economic viability. Pathological investigation of osteoarthritis reveals that low-level inflammation plays a crucial role in disease development. Joint inflammation stimulates neoangiogenesis and accompanying neuronal growth, with the degree of microvascular invasion being correlated with more severe pain in animal models. These neovessels provide a target for embolization however, the microscopic effects of this intervention are yet to be elucidated. The side effects of GAE have been extensively investigated with no severe adverse events being recorded. Skin discoloration and puncture site hematoma are the most common, occurring in 10%-65% and 0%-17% of patients respectively. The literature also discusses ways to minimize these events. Phase one studies provide promising evidence of efficacy, demonstrating an 80% improvement in Visual Analogue Scale (VAS) and a mean difference of 36.8 in Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores at 24-months. These positive signals are also supported by a single randomized control trial. A single study has been completed regarding the cost of GAE, however further work is needed. The GAE literature demonstrates a safe procedure with promising initial evidence of efficacy. Future work should further elucidate the pathology of osteoarthritis and ways in which embolization modifies this process, alongside providing further randomized control evidence that aligns with the recommendations from the National Institute for Health and Care Excellence. The future of GAE is exciting!

High-Grade Prostate Cancer Invading the Vagina: A Case Report of an Unusual Prostate Cancer Diagnosed in a Man with Persistent Mullerian Duct Syndrome.

We report an extremely rare case of locally advanced prostate cancer in a phenotypic male patient with persistent müllerian duct syndrome. The patient underwent a robot-assisted retzius-sparing radical prostatectomy, bilateral pelvic lymph node dissection, radical hysterectomy, vaginectomy, and salpingo-ophorectomy. He was continent at 3 months follow-up. His follow-up PSA has steadily increased up to 1.4 ng/mL 6 months following surgery and his PSMA-PET scan showed bone metastasis with no local recurrence, and androgen deprivation therapy was started along with docetaxel chemotherapy. Prostate cancer in patients with DSD is extremely rare and can manifest itself with a low PSA, although aggressive cancer.

The State of Evidence in Prostate Artery Embolization.

Prostate artery embolization (PAE) has emerged over the past two decades as a minimally invasive, nonsurgical treatment for benign prostatic hypertrophy (BPH). While the majority of evidence for PAE stems from retrospective cohort studies, several seminal randomized controlled trials have been performed comparing short-term outcomes of PAE to transurethral resection of prostate (TURP) and against a sham procedure. Across clinical trials, PAE demonstrates consistent improvement in urological symptoms and quality of life in patients with BPH with low complication rates. When compared to TURP, the results are comparable, but there is a trend for better outcomes in certain clinical parameters with TURP. PAE is a suitable option for patients who are not surgical candidates, prefer nonsurgical treatment with an earlier return to routine activities, and wish to better preserve sexual function.

Updates on Preprocedural Evaluation and Patient Selection for Prostatic Artery Embolization.

Prostatic artery embolization (PAE) is a safe and effective treatment for benign prostatic hyperplasia. Patient evaluation is a critical and important part of this growing practice. History taking should include symptoms score evaluations for lower urinary tract symptoms, erectile function, and prostatitis symptoms score. The objective evaluations commonly include measurement of prostate specific antigen, postvoid residual volume, and uroflowmetry as well as urodynamic studies in selective patients. Imaging evaluation may include computed tomography angiography or magnetic resonance angiography, elucidating prostate volume, prostate gland morphology, vasculature, and prostate cancer. With evolving knowledge on PAE, we aim to discuss patient evaluation and selection based on updated evidence and discuss specific scenarios.

Proportion of Concentrate in the Diet of Early Lactation Dairy Cows Has Contrasting Effects on Circulating Leukocyte Global Transcriptomic Profiles, Health and Fertility According to Parity.

The functionality of circulating leukocytes in dairy cows is suppressed after calving, with negative energy balance as a risk factor. Leukocyte transcriptomic profiles were compared separately in 44 multiparous (MP) and 18 primiparous (PP) Holstein-Friesian cows receiving diets differing in concentrate proportion to test whether immune dysfunction could be mitigated by appropriate nutrition. After calving, cows were offered either (1) low concentrate (LC); (2) medium concentrate (MC) or (3) high concentrate (HC) diets with proportions of concentrate to grass silage of 30%:70%, 50%:50% and 70%:30%, respectively. Cow phenotype data collected included circulating metabolites, milk yield and health and fertility records. RNA sequencing of circulating leukocytes at 14 days in milk was performed. The HC diet improved energy balance in both age groups. There were more differentially expressed genes in PP than MP cows (460 vs. 173, HC vs. LC comparison) with few overlaps. The MP cows on the LC diet showed upregulation of the complement and coagulation cascade and innate immune defence mechanisms against pathogens and had a trend of more cases of mastitis and poorer fertility. In contrast, the PP cows on the HC diet showed greater immune responses based on both gene expression and phenotypic data and longer interval of calving to conception. The leukocytes of MP and PP cows therefore responded differentially to the diets between age, nutrient supply and immunity affecting their health and subsequent fertility.

The STREAM Trial (Prostatic Artery Embolization for the Treatment of Benign Prostatic Hyperplasia) 24-Month Clinical and Radiological Outcomes.

PURPOSE: To establish factors predictive of success prior to Prostate Artery Embolization (PAE) with MRI imaging. MATERIALS AND METHODS: A prospective cohort study of 50 patients with Benign Prostatic Hyperplasia (BPH) were treated with PAE in a single institution. Patients had moderate to severe symptoms of BPH refractory to medical management for at least 6 months. Patients were imaged with multiparametric MRI imaging pre-PAE and at 3 months, 12 months and 24 months post-PAE. Clinical success was measured with IPSS, IIEF and EQ-5D-5L quality of life questionnaires. RESULTS: The technical success was 48/50 (96%).The mean age of the group was 67 (range 54-83). The mean IPSS score pre-PAE was 21 and at 24 months was 8 (p < 0.001). There was no deterioration in erectile function. The mean volume of the prostate post-PAE was reduced at 3 and 12 months post-PAE but not significantly different at 24 months. This did not correlate with the IPSS score. Patients with median lobe enlargement has similar symptomatic improvement as those without median lobe enlargement. Internally within the prostate patients with adenomatous-dominant BPH initially did better than patients with stromal enlargement; however, at 24 months patients with stromal enlargement of the prostate improved greatest. Initial volume of the prostate was not a good predictor of clinical success. CONCLUSION: PAE is a safe and effective treatment strategy for treating men with BPH. Patients with Adenomatous BPH clinically do better until 12 months but not at 24 months. Initial prostate volume does not affect outcome, and patients with median lobe enlargement do as well as those without.

Comparison of total-mixed-ration and feed-to-yield strategies on blood profiles and dairy cow health.

Seventy-two Holstein-Friesian dairy cows were offered the same amount of concentrates over the first 140 days of lactation, by either a 'total-mixed-ration' or a 'feed-to-yield' strategy. The effects on blood profiles and cow health were examined. Cows on total-mixed-ration were offered a mixed ration comprising grass silage and concentrates (50:50 dry matter basis). Cows on feed-to-yield were offered a basal mixed ration (grass silage plus 6 kg concentrates/cow/day) plus additional concentrates via an out-of-parlour feeding system, calculated according to each individual cow's milk yield during the previous week. Cows on total-mixed-ration had a higher mean haemoglobin, packed cell volume and lymphocyte percentage. Concentrate allocation strategy had no effect on serum haptoglobin concentrations, interferon-gamma production of pokeweed mitogen-stimulated whole blood culture, the incidence of clinical or subclinical mastitis, lameness, respiratory or digestive problems and no strong relationships were identified between production parameters with serum metabolites, inflammatory and immune measures. This study demonstrates small physiological differences in metabolic parameters, and no differences in inflammatory or immune parameters, when allocating concentrates by total-mixed-ration or feed-to-yield.

Prostatic Artery Embolization (PAE) for Benign Prostatic Hyperplasia (BPH) with Haematuria in the Absence of an Upper Urinary Tract Pathology.

PURPOSE: To assess the effectiveness of prostate artery embolization (PAE) in the control of haematuria and in patients with benign prostatic hyperplasia (BPH) and normal upper urinary tracts. SUBJECTS/PATIENTS: Twelve consecutive patients with haematuria were included in the prospective study. All patients had prior imaging and cystoscopy to exclude other causes of haematuria. Patients prostate arteries were embolized with particles (200-500 µm), and they were followed up at 3, 12 and 18 months following the procedure. QOL questionnaires, IPSS, IIEF and clinical review were all employed to assess the success of the treatment. To allow useful comparison, patients were age- and prostate volume-matched and compared to patients treated with PAE for BPH without haematuria. RESULTS: All 12/12 cases were technically successful with bilateral PAE being performed. All cases of haematuria resolved by the 3-month follow-up (100%). There was one case of recurrence during the 12-month follow-up (overall clinical success at 18 months 92%). This was due to over anticoagulation and ceased once corrected. There was a reduction in lower urinary tract symptoms noted by improvements in QOL indices, IPSS and IIEF. There was continued success even if the patient was subsequently anticoagulated. There was no associated sexual dysfunction. There was more prostatic arterial branching and volume of embolic required to achieve stasis in BPH and haematuria than in BPH alone (p < 0.05). CONCLUSION: PAE is a very useful technique for controlling the quite debilitating condition of haematuria in patients with visible haematuria of prostatic origin. Controlling haematuria and BPH allows a significant improvement in QOL.

Effects of Sublingual Glyceryl Trinitrate Administration on the Quality of Preprocedure CT Angiography Performed to Plan Prostate Artery Embolization.

PURPOSE: To determine the effects of sublingual glyceryl trinitrate (GTN) on the quality of planning computed tomography (CT) angiography performed prior to prostate artery embolization (PAE). MATERIALS AND METHODS: A retrospective cohort study was performed on patients who had previously undergone CT angiography before a procedure for PAE at our institution. Early CT angiography studies for PAE at our single center had initially been performed without GTN. These were compared to subsequent CT angiography studies that had been performed with GTN, after a previously implemented change in practice. Prostate arteries were examined by 2 blinded observers for peak enhancement (Hounsfield units [HU]) and lumen diameter. In addition, assessors' interpretation of the prostate artery origin from CT angiography was compared with the true anatomy demonstrated at the time of procedure. RESULTS: A total of 16 patients, corresponding to 32 prostate arteries, were examined on CT angiography. Mean diameter of the prostate artery was found to be significantly greater in those receiving GTN (2.2 mm vs. 1.6 mm, P < .001). Peak prostate artery enhancement was also greater in the GTN group (218 HU vs 173 HU, P = 0.042). Observers correctly identified the prostate artery origin more frequently in the GTN group; however, this difference was not statistically significant (56% vs 25%, odds ratio = 3.9, P = .149). CONCLUSIONS: The administration of sublingual GTN immediately prior to CT angiography is associated with a significant increase in prostate artery diameter and peak opacification. This was not associated with a statistically significant increase in the ability of observers to correctly identify the origin of the prostate artery.

Retrograde transileal conduit stent placement for obstructed uropathy--success of primary and exchange stent placement.

PURPOSE: To assess the safety, success, and complications associated with retrograde ureteric stent insertion via the ileal conduit. MATERIALS AND METHODS: The study population comprised 35 consecutive patients (17 men and 18 women; mean age, 55 y; age range, 40-75 y) requiring primary (20 stents) and exchange (70 stents) retrograde ureteric stent insertion via the ileal conduit over a 3-year period. Patient demographic data, procedural and technical data, and clinical follow-up data were collected. RESULTS: Technical success was 90% (18 of 20) for primary stent placement and 100% (70 of 70) for stent exchange. There were two immediate complications (< 24 h) of sepsis and ureteric injury and one early complication (> 25 h but < 30 d) of sepsis requiring observation and medical management. Difficult procedures (defined as a fluoroscopy screening time > 31 min) and technical failures were found to be associated with encrusted stents visualized on prior computed tomography (P = .012), increased length of ileal conduit (> 20 cm) (P = .023), and ileal conduit kink (< 90 degrees) (P = .032). Only the occurrence of encrusted stents visualized on prior computed tomography (P = .022) was associated with complications. CONCLUSIONS: Retrograde placement of ureteric stents via the ileal conduit is safe and effective. Retrograde stent placement should be considered the treatment option of choice for a first-time occurrence of obstructive uropathy at the ureteroileal anastomosis.

Microwave ablation of pulmonary malignancies using a novel high-energy antenna system.

PURPOSE: To evaluate the technical success, safety, and imaging follow-up of malignant pulmonary nodules treated with a novel high-energy percutaneous microwave ablation (MWA) system. METHODS: Between July 2010 and September 2011, a total of 23 patients, 12 men, mean age 68 (range 30-87) years with 29 pulmonary malignancies of median diameter 19 (range 8-57) mm, underwent computed tomography (CT)-guided MWA with a 16G microwave needle antenna enabling power up to 180 W. Technical success was defined as needle placement in the intended lesion without death or serious injury. Adequacy of ablation was assessed at 24 h on contrast-enhanced CT. Circumferential solid or ground glass opacification >5 mm was used to define an ideal ablation. Local tumor recurrence was assessed at 1, 3, and 6 months after ablation on contrast-enhanced CT. RESULTS: MWA was technically successful in 93 % (n = 27). Mean ablation duration was 3.6 (range 1-9) min. Ten patients (43 %) developed a pneumothorax as a result of the MWA; only 3 (13 %) required placement of a chest drain. Thirty-day mortality rate was 0 %. The mean hospital stay was 1.5 (range 1-7) days. A total of 22 lesions (75 %) were surrounded by ≥5 mm ground glass or solid opacification after the procedure. At a median follow-up of 6 months, local recurrence was identified in 3 out of 26 lesions, giving a local control rate of 88 %. CONCLUSION: MWA using a high-power antenna of pulmonary malignancies is safe, technically achievable, and enables fast ablation times.

Neurenteric cyst of the anterior cranial fossa: case report and literature review.

Intracranial neurenteric cysts are rare congenital lesions that typically occur in the posterior fossa. We report a case of a 70-year-old gentleman presenting with gait disturbance, found to have a neurenteric cyst primarily arising from and expanding the sella turcica. A review of the literature revealed 27 reports of supratentorial neurenteric cysts. Clinical presentation, radiological characteristics, treatment, prognosis and embryological origin are discussed. Intracranial neurenteric cysts should be included in the differential with any well-demarcated cystic lesion without enhancement on magnetic resonance imaging (MRI). Complete surgical excision is the treatment of choice, with good prognosis.

Electrospray-assisted laser desorption ionization mass spectrometry (ELDI-MS) with an infrared laser for characterizing peptides and proteins.

An electrospray-assisted laser desorption/ionization source with an infrared OPO laser (IR-ELDI) was constructed and optimized for peptide and protein mass spectrometry analysis. Similar to ELDI with an ultraviolet laser, IR-ELDI generates multiply charged molecules for peptides and proteins measured under ambient sampling conditions. Both samples in the dried state and analyte solutions can be directly measured by IR-ELDI without the presence of a conventional MALDI matrix. However, the analysis of sample solutions is shown to greatly enhance the sensitivity of the mass spectrometry measurement, as a 100-fold sensitivity gain for peptide measurements was measured. The limit of detection of IR-ELDI was determined to be 250 fmol for bradykinin (1.1 kDa), 100 fmol for ubiquitin (8.6 kDa), and 500 fmol for carbonic anhydrase (29 kDa). IR-ELDI is amenable for MS and MSn analysis for proteins up to 80 kDa transferrin. IR-ELDI-MS may be a useful tool for protein sequencing analysis from complex biological matrices, with minimal sample preparation required.