26 results on '"The Churchill hospital"'
Search Results
2. Changes in epicardial and visceral adipose tissue depots following bariatric surgery and their effect on cardiac geometry
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Henry, J. A., Abdesselam, I., Deal, O., Lewis, A. J., Rayner, J., Bernard, M., Dutour, A., Gaborit, B., Kober, F., Soghomonian, A., Sgromo, B., Byrne, J., Bege, T., Neubauer, S., Borlaug, B. A., Rider, O. J., University of Oxford, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance Publique - Hôpitaux de Marseille (APHM), The Churchill Hospital, University Hospital Southampton NHS Foundation Trust, Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU), and Mayo Clinic [Rochester]
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obesity ,Endocrinology, Diabetes and Metabolism ,bariatric surgery ,cardiac geometry ,cardiac remodelling ,epicardiac adipose tissue ,weight loss ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
IntroductionObesity affects cardiac geometry, causing both eccentric (due to increased cardiac output) and concentric (due to insulin resistance) remodelling. Following bariatric surgery, reversal of both processes should occur. Furthermore, epicardial adipose tissue loss following bariatric surgery may reduce pericardial restraint, allowing further chamber expansion. We investigated these changes in a serial imaging study of adipose depots and cardiac geometry following bariatric surgery.Methods62 patients underwent cardiac magnetic resonance (CMR) before and after bariatric surgery, including 36 with short-term (median 212 days), 37 medium-term (median 428 days) and 32 long-term (median 1030 days) follow-up. CMR was used to assess cardiac geometry (left atrial volume (LAV) and left ventricular end-diastolic volume (LVEDV)), LV mass (LVM) and LV eccentricity index (LVei – a marker of pericardial restraint). Abdominal visceral (VAT) and epicardial (EAT) adipose tissue were also measured.ResultsPatients on average had lost 21kg (38.9% excess weight loss, EWL) at 212 days and 36kg (64.7% EWL) at 1030 days following bariatric surgery. Most VAT and EAT loss (43% and 14%, pConclusionsCardiac volumes show a biphasic response to weight loss, initially becoming smaller and then returning to pre-operative sizes by 1030 days. We propose this is due to an initial reversal of eccentric remodelling followed by reversal of concentric remodelling. Furthermore, we provide evidence for a role of EAT contributing to pericardial restraint, with EAT loss improving markers of pericardial restraint.
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- 2023
3. Two-Year Outcomes of Prostatic Artery Embolization for Symptomatic Benign Prostatic Hyperplasia: An International, Multicenter, Prospective Study.
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Sapoval MR, Bhatia S, Déan C, Rampoldi A, Carnevale FC, Bent C, Tapping CR, Bongiovanni S, Taylor J, Brower JS, Rush M, McWilliams JP, and Little MW
- Abstract
Purpose: To describe clinical outcomes among patients with benign prostatic hyperplasia (BPH) 24 months following prostatic artery embolization (PAE)., Materials and Methods: This was an international, multicenter, prospective trial of males with BPH with lower urinary tract symptoms (LUTS) or acute urinary retention (AUR) treated with PAE. The primary outcome was the 12 month change in the International Prostate Symptom Score (IPSS) for patients referred for bothersome LUTS, or urinary catheter independence for patients treated for AUR. Secondary outcome measures included changes in IPSS at 3 and 24 months, changes in quality of life (QoL), changes in the Sexual Health Inventory for Men (SHIM) questionnaire, technical success rate, and adverse events (AEs). Data were summarized using descriptive statistics., Results: Four hundred seventy-eight consecutive patients underwent PAE (bothersome LUTS: N = 405; AUR: N = 73), mean age was 70 years. For patients treated for bothersome LUTS, mean total IPSS at baseline was 21.8 and decreased to 9.3, 10.6, and 11.2 at 3, 12, and 24 months following PAE, respectively (all p < 0.001); QoL at baseline was 4.7 and decreased to 2.0, 2.1, and 2.3 at 3, 12, and 24 months, respectively (all p < 0.001). The mean SHIM score at baseline and 12 months following PAE was 13.8 and 13.9, respectively. Of the 73 patients treated for AUR, 48 (65.8%) had their indwelling catheter removed within 3 months of PAE and remained catheter free at 24 months. Fifty-five patients (11.5%) experienced ≥ 1 AE and 10 (2.1%) experienced a serious AE., Conclusion: PAE is a safe and effective treatment for symptomatic BPH and LUTS. Level of Evidence Level 3 Trial registration ClinicalTrials.gov NCT03527589., (© 2024. The Author(s).)
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- 2024
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4. Dosimetric comparison of proton therapy and CyberKnife in stereotactic body radiation therapy for liver cancers.
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Shyllon S, Penfold S, Dalfsen R, Kirkness E, Hug B, Rowshanfarzad P, Devlin P, Tang C, Le H, Gorayski P, Grogan G, Kearvell R, and Ebert MA
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- Humans, Dose-Response Relationship, Radiation, Carcinoma, Hepatocellular radiotherapy, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular surgery, Male, Retrospective Studies, Liver Neoplasms radiotherapy, Liver Neoplasms diagnostic imaging, Liver Neoplasms surgery, Radiosurgery, Proton Therapy, Radiometry, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted
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Stereotactic body radiation therapy (SBRT) has been increasingly used for the ablation of liver tumours. CyberKnife and proton beam therapy (PBT) are two advanced treatment technologies suitable to deliver SBRT with high dose conformity and steep dose gradients. However, there is very limited data comparing the dosimetric characteristics of CyberKnife to PBT for liver SBRT. PBT and CyberKnife plans were retrospectively generated using 4DCT datasets of ten patients who were previously treated for hepatocellular carcinoma (HCC, N = 5) and liver metastasis (N = 5). Dose volume histogram data was assessed and compared against selected criteria; given a dose prescription of 54 Gy in 3 fractions for liver metastases and 45 Gy in 3 fractions for HCC, with previously published consensus-based normal tissue dose constraints. Comparison of evaluation parameters showed a statistically significant difference for target volume coverage and liver, lungs and spinal cord (p < 0.05) dose, while chest wall and skin did not indicate a significant difference between the two modalities. A number of optimal normal tissue constraints was violated by both the CyberKnife and proton plans for the same patients due to proximity of tumour to chest wall. PBT resulted in greater organ sparing, the extent of which was mainly dependent on tumour location. Tumours located on the liver periphery experienced the largest increase in organ sparing. Organ sparing for CyberKnife was comparable with PBT for small target volumes., (© 2024. The Author(s).)
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- 2024
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5. Defatting of donor transplant livers during normothermic perfusion-a randomised clinical trial: study protocol for the DeFat study.
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Abbas SH, Ceresa CDL, Hodson L, Nasralla D, Watson CJE, Mergental H, Coussios C, Kaloyirou F, Brusby K, Mora A, Thomas H, Kounali D, Keen K, Pollok JM, Gaurav R, Iype S, Jassem W, Perera MTP, Hakeem AR, Knight S, and Friend PJ
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- Humans, Tissue Donors supply & distribution, Liver pathology, Multicenter Studies as Topic, Organ Preservation methods, Time Factors, Treatment Outcome, Liver Transplantation methods, Perfusion methods, Randomized Controlled Trials as Topic, Fatty Liver therapy
- Abstract
Background: Liver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes., Methods: In the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months)., Discussion: This study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths., Trial Registration: ISRCTN ISRCTN14957538. Registered in October 2022., (© 2024. The Author(s).)
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- 2024
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6. Congenital hallux valgus occurs in Fibrodysplasia Ossificans Progressiva and BMPR1B-associated dysplasia: an important distinction.
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Shirodkar D, Smithson SF, Keen R, Lester T, Banos-Pinero B, and Burren CP
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- Humans, Female, Infant, Myositis Ossificans genetics, Hallux Valgus genetics, Hallux Valgus diagnostic imaging, Bone Morphogenetic Protein Receptors, Type I genetics
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Background: Fibrodysplasia Ossificans Progressiva (FOP; OMIM #135100) is an ultrarare genetic disorder characterised by congenital bilateral hallux valgus (CBHV), intermittent soft tissue swellings and progressive heterotopic ossification. We report a three-month-old girl with great toe abnormalities similar to FOP, in whom comprehensive clinical workup and genetic investigations illustrates an alternative diagnosis., Case Presentation: A three-month-old girl presented with CBHV. The antenatal period was unremarkable, she was born by spontaneous vaginal delivery with an uneventful subsequent course, except for maternal concern of her bent toes which received reassurance from several health professionals. Her mother's persisting concerns were explored via the internet and social media leading her to request referral to an expert bone centre for consideration of FOP. On examination, she was thriving, there was no dysmorphism, subcutaneous lumps, skeletal or extra-skeletal deformity except for shortened great toes with lateral deviation of the proximal and distal phalanges. FOP was a feasible diagnosis, for which CBHV is highlighted as an early sign. A cautionary potential diagnosis of FOP was counselled, including advice to defer intramuscular immunisations until genetic results available. Genetic investigation was undertaken through rapid whole genomic sequencing (WGS), with analysis of data from a skeletal dysplasia gene panel, which demonstrated no ACVR1variants. The only finding was a heterozygous variant of unknown significance in BMPR1B (c1460T>A, p.(Val487Asp)), which encodes a bone morphogenic receptor involved in brachydactyly syndromes A1, A2 and D and acromesomelic dysplasia 3 (only the latter being an autosomal recessive condition)., Conclusion: This report highlights that CBHV serves as a vital diagnostic indicator of FOP and affected infants should be considered and investigated for FOP, including precautionary management whilst awaiting genetic studies. The second educational aspect is that CBHV may not represent a generalised skeletal disorder, or one much less significant than FOP. Receptor-ligand BMP and Activins mediated interactions are instrumental in the intricate embryology of the great toe. Recognition of non-FOP conditions caused by alterations in different genes are likely to increase with new genomic technology and large gene panels, enhancing understanding of bone signaling pathways., (© 2024. The Author(s).)
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- 2024
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7. Functional Impairment in Small Airways Associated With the Breathlessness Symptoms in Long-Coronavirus Disease.
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Kim M, Hwang J, Grist JT, Abueid G, Yoon SH, Grau V, Fraser E, and Gleeson FV
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- Humans, Lung diagnostic imaging, Lung pathology, Respiration, Magnetic Resonance Imaging methods, Dyspnea diagnostic imaging, Xenon Isotopes, Post-Acute COVID-19 Syndrome
- Abstract
Purpose: This study aimed to determine the association between functional impairment in small airways and symptoms of dyspnea in patients with Long-coronavirus disease (COVID), using imaging and computational modeling analysis., Patients and Methods: Thirty-four patients with Long-COVID underwent thoracic computed tomography and hyperpolarized Xenon-129 magnetic resonance imaging (HP Xe MRI) scans. Twenty-two answered dyspnea-12 questionnaires. We used a computed tomography-based full-scale airway network (FAN) flow model to simulate pulmonary ventilation. The ventilation distribution projected on a coronal plane and the percentage lobar ventilation modeled in the FAN model were compared with the HP Xe MRI data. To assess the ventilation heterogeneity in small airways, we calculated the fractal dimensions of the impaired ventilation regions in the HP Xe MRI and FAN models., Results: The ventilation distribution projected on a coronal plane showed an excellent resemblance between HP Xe MRI scans and FAN models (structure similarity index: 0.87 ± 0.04). In both the image and the model, the existence of large clustered ventilation defects was not identifiable regardless of dyspnea severity. The percentage lobar ventilation of the HP Xe MRI and FAN model showed a strong correlation (ρ = 0.63, P < 0.001). The difference in the fractal dimension of impaired ventilation zones between the low and high dyspnea-12 score groups was significant (HP Xe MRI: 1.97 [1.89 to 2.04] and 2.08 [2.06 to 2.14], P = 0.005; FAN: 2.60 [2.59 to 2.64] and 2.64 [2.63 to 2.65], P = 0.056)., Conclusions: This study has identified a potential association of small airway functional impairment with breathlessness in Long-COVID, using fractal analysis of HP Xe MRI scans and FAN models., Competing Interests: J.H. has received the National Research Foundation of Korea grant funded by the Korean government (#NRF-2019R1I1A1A01063383). The remaining authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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8. Living donor uterus transplant in the UK: A case report.
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Jones BP, Vali S, Saso S, Devaney A, Bracewell-Milnes T, Nicopoullos J, Thum MY, Kaur B, Roufosse C, Stewart V, Bharwani N, Ogbemudia A, Barnardo M, Dimitrov P, Klucniks A, Katz R, Johannesson L, Diaz Garcia C, Udupa V, Friend P, Quiroga I, and Smith JR
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- Female, Humans, Living Donors, Uterus surgery, United Kingdom, Organ Transplantation, Transplants
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- 2024
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9. Spore-FP1 tuberculosis mucosal vaccine candidate is highly protective in guinea pigs but fails to improve on BCG-conferred protection in non-human primates.
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White AD, Tran AC, Sibley L, Sarfas C, Morrison AL, Lawrence S, Dennis M, Clark S, Zadi S, Lanni F, Rayner E, Copland A, Hart P, Diogo GR, Paul MJ, Kim M, Gleeson F, Salguero FJ, Singh M, Stehr M, Cutting SM, Basile JI, Rottenberg ME, Williams A, Sharpe SA, and Reljic R
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- Guinea Pigs, Animals, BCG Vaccine, Macaca mulatta, Antigens, Bacterial, Spores, Tuberculosis Vaccines, Tuberculosis prevention & control, Mycobacterium bovis, Mycobacterium tuberculosis
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Tuberculosis remains a major health threat globally and a more effective vaccine than the current Bacillus Calmette Guerin (BCG) is required, either to replace or boost it. The Spore-FP1 mucosal vaccine candidate is based on the fusion protein of Ag85B-Acr-HBHA/heparin-binding domain, adsorbed on the surface of inactivated Bacillus subtilis spores. The candidate conferred significant protection against Mycobacterium. tuberculosis challenge in naïve guinea pigs and markedly improved protection in the lungs and spleens of animals primed with BCG. We then immunized rhesus macaques with BCG intradermally, and subsequently boosted with one intradermal and one aerosol dose of Spore-FP1, prior to challenge with low dose aerosolized M. tuberculosis Erdman strain. Following vaccination, animals did not show any adverse reactions and displayed higher antigen specific cellular and antibody immune responses compared to BCG alone but this did not translate into significant improvement in disease pathology or bacterial burden in the organs., Competing Interests: Co-author GD is now an employee of Janssen, Pharmaceutical Companies of Johnson & Johnson. Author SMC was employed by the company Sporegen Ltd. Author MSi and MSt were employed by the company Lionex GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor JI declared a shared parent affiliation with the authors AT, AC, PH, GD, MP, MK, and RR at the time of review., (Copyright © 2023 White, Tran, Sibley, Sarfas, Morrison, Lawrence, Dennis, Clark, Zadi, Lanni, Rayner, Copland, Hart, Diogo, Paul, Kim, Gleeson, Salguero, Singh, Stehr, Cutting, Basile, Rottenberg, Williams, Sharpe and Reljic.)
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- 2023
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10. Attitudes, knowledge, and perceptions among women toward uterus transplantation and donation in the United Kingdom.
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Vali S, Jones BP, Sheikh S, Saso S, Quiroga I, and Smith JR
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Objective: To assess the motivations and perceptions of the general public in the United Kingdom toward donating their uterus for Uterus Transplantation after death (UTx)., Design: A cross sectional study., Setting: A 32-item electronic questionnaire., Population: One hundred fifty nine females over the age of 16 living in the United Kingdom, consented and took part in the study., Main Outcome Measures: The motivations and perceptions toward UTx among the general public including the willingness to donate and barriers preventing donation., Results: One hundred fifty nine women completed the questionnaire. The majority had never heard of UTx ( n = 107, 71%) and most were not aware the uterus could be donated after death ( n = 130, 92%). 43% of the cohort were willing to donate their uterus after death ( n = 57). 8% stated they wished to donate their organs but not their uterus ( n = 10). 30% of women ( n = 42) believed the child born following UTx would have genetic links to the donor. Over half of the respondents ( n = 65, 51%) strongly agreed or agreed they would feel joy in the knowledge that donation would lead to bringing a new life into the world. A quarter of respondents strongly agreed or agreed ( n = 45, 25%) that the use of their uterus by another woman would feel like an extension of life., Conclusion: The findings indicate a favorable opinion toward UTx and a positive attitude toward donation of the uterus after death among the general public in the United Kingdom. The findings also highlight the need for education around UTx now this therapeutic option is available., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vali, Jones, Sheikh, Saso, Quiroga and Smith.)
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- 2023
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11. The prevalence and phenotypic range associated with biallelic PKDCC variants.
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Pagnamenta AT, Belles RS, Salbert BA, Wentzensen IM, Guillen Sacoto MJ, Santos FJR, Caffo A, Ferla M, Banos-Pinero B, Pawliczak K, Makvand M, Najmabadi H, Maroofian R, Lester T, Yanez-Felix AL, Villarroel-Cortes CE, Xia F, Al Fayez K, Al Hashem A, Shears D, Irving M, Offiah AC, Kariminejad A, and Taylor JC
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- Humans, Hedgehog Proteins, Prevalence, RNA Splice Sites, Dwarfism, Osteochondrodysplasias pathology
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PKDCC encodes a component of Hedgehog signalling required for normal chondrogenesis and skeletal development. Although biallelic PKDCC variants have been implicated in rhizomelic shortening of limbs with variable dysmorphic features, this association was based on just two patients. In this study, data from the 100 000 Genomes Project was used in conjunction with exome sequencing and panel-testing results accessed via international collaboration to assemble a cohort of eight individuals from seven independent families with biallelic PKDCC variants. The allelic series included six frameshifts, a previously described splice-donor site variant and a likely pathogenic missense variant observed in two families that was supported by in silico structural modelling. Database queries suggested that the prevalence of this condition is between 1 of 127 and 1 of 721 in clinical cohorts with skeletal dysplasia of unknown aetiology. Clinical assessments, combined with data from previously published cases, indicate a predominantly upper limb involvement. Micrognathia, hypertelorism and hearing loss appear to be commonly co-occurring features. In conclusion, this study strengthens the link between biallelic inactivation of PKDCC and rhizomelic limb-shortening and will enable clinical testing laboratories to better interpret variants in this gene., (© 2023 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)
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- 2023
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12. Gas exchange and ventilation imaging of healthy and COPD subjects using hyperpolarized xenon-129 MRI and a 3D alveolar gas-exchange model.
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Doganay O, Kim M, and Gleeson FV
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- Humans, Lung pathology, Magnetic Resonance Imaging methods, Xenon, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Emphysema
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Objectives: To investigate the utility of hyperpolarized xenon-129 (HPX) gas-exchange magnetic resonance imaging (MRI) and modeling in a chronic obstructive pulmonary disease (COPD) cohort in comparison to a minimal CT-diagnosed emphysema (MCTE) cohort and a healthy cohort., Methods: A total of 25 subjects were involved in this study including COPD (n = 8), MCTE (n = 3), and healthy (n = 14) subjects. The COPD subjects were scanned using HPX ventilation, gas-exchange MRI, and volumetric CT. The healthy subjects were scanned using the same HPX gas-exchange MRI protocol with 9 of them scanned twice, 3 weeks apart. The coefficient of variation (CV) was used to quantify image heterogeneities. A three-dimensional computational fluid dynamic (CFD) model of gas exchange was used to derive functional volumes of pulmonary tissue, capillaries, and veins., Results: The CVs of gas distributions in the images showed that there was a statistically significant difference between the COPD and healthy subjects (p < 0.0001). The functional volumes of pulmonary tissue, capillaries, and veins were significantly lower in the subjects with COPD than in the healthy subjects (p < 0.001). The functional volume of pulmonary tissue was found to be (i) statistically different between the healthy and MCTE groups (p = 0.02) and (ii) dependent on the age of the subjects in the healthy group (p = 0.0008) while their CVs (p = 0.13) were not., Conclusion: The novel HPX gas-exchange MRI and CFD model distinguished the healthy cohort from the MCTE and COPD cohorts. The proposed technique also showed that the functional volume of pulmonary tissue decreases with aging in the healthy group., Key Points: • The ventilation and gas-exchange imaging with hyperpolarized xenon-129 MRI has enabled the identification of gas-exchange variation between COPD and healthy groups. • This novel technique was promising to be sensitive to minimal CT-diagnosed emphysema and age-related changes in gas-exchange parameter in a small pilot cohort., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)
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- 2023
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13. Airway clearance techniques compared to no airway clearance techniques for cystic fibrosis.
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Warnock L and Gates A
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- Adult, Child, Humans, Cystic Fibrosis Transmembrane Conductance Regulator, Cough etiology, Radioactive Tracers, Forced Expiratory Volume, Cystic Fibrosis complications, Cystic Fibrosis therapy
- Abstract
Background: Cystic fibrosis (CF) is an inherited progressive life-limiting disease characterised by the build-up of abnormally thick, sticky mucus affecting mostly the lungs, pancreas, and digestive system. Airway clearance techniques (ACTs), traditionally referred to as chest physiotherapy, are recommended as part of a complex treatment programme for people with CF. The aim of an ACTs is to enhance mucociliary clearance and remove viscous secretions from the airways within the lung to prevent distal airway obstruction. This reduces the infective burden and associated inflammatory effects on the airway epithelia. There are a number of recognised ACTs, none of which have shown superiority in improving short-term outcomes related to mucus transport. This systematic review, which has been updated regularly since it was first published in 2000, considers the efficacy of ACTs compared to not performing any ACT in adults and children with CF. It is important to continue to review this evidence, particularly the long-term outcomes, given the recent introduction of highly effective modulator therapies and the improved health outcomes and potential changes to CF management associated with these drugs., Objectives: To determine the effectiveness and acceptability of airway clearance techniques compared to no airway clearance techniques or cough alone in people with cystic fibrosis., Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings, to 17 October 2022. We searched ongoing trials registers (Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform) to 7 November 2022., Selection Criteria: We included randomised or quasi-randomised studies that compared airway clearance techniques (chest physiotherapy) with no airway clearance techniques or spontaneous cough alone in people with CF., Data Collection and Analysis: Both review authors independently assessed study eligibility, extracted data, and assessed the risk of bias of the included studies. We used GRADE methodology to assess the certainty of the evidence., Main Results: We included 11 cross-over studies (153 participants) and one parallel study (41 participants). There were differences between studies in how the interventions were delivered, with several intervention groups combining more than one ACT. One study used autogenic drainage; five used conventional chest physiotherapy; nine used positive expiratory pressure (PEP), with one study varying the water pressure between arms; three studies used oscillating PEP; two used exercise; and two used high-frequency chest wall oscillation (HFCWO). Of the 12 included studies, 10 were single-treatment studies, and two delivered the intervention over two consecutive days (once daily in one study, twice daily in the second). This substantial heterogeneity in the treatment interventions precluded pooling of data for meta-analysis. Blinding of participants, caregivers, and clinicians is impossible in airway clearance studies; we therefore judged all studies at unclear risk of performance bias. Lack of information in eight studies made assessment of risk of bias unclear for most other domains. We rated the certainty of evidence as low or very low due to the short-term cross-over trial design, small numbers of participants, and uncertain risk of bias across most or all domains. Six studies (84 participants) reported no effect on pulmonary function variables following intervention; but one study (14 participants) reported an improvement in pulmonary function following the intervention in some of the treatment groups. Two studies reported lung clearance index: one (41 participants) found a variable response to treatment with HFCWO, whilst another (15 participants) found no effect on lung clearance index with PEP therapy (low-certainty evidence). Five studies (55 participants) reported that ACTs, including coughing, increased radioactive tracer clearance compared to control, while a further study (eight participants) reported no improvement in radioactive tracer clearance when comparing PEP to control, although coughing was discouraged during the PEP intervention. We rated the certainty of evidence on the effect of ACTs on radioactive tracer clearance as very low. Four studies (46 participants) investigated the weight of mucus cleared from the lungs and reported greater secretions during chest physiotherapy compared to a control. One study (18 participants) reported no differences in sputum weight (very low-certainty evidence)., Authors' Conclusions: The evidence from this review shows that ACTs may have short-term effects on increasing mucus transport in people with CF. All included studies had short-term follow-up; consequently, we were unable to draw any conclusions on the long-term effects of ACTs compared to no ACTs in people with CF. The evidence in this review represents the use of airway clearance techniques in a CF population before widespread use of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. Further research is needed to determine the effectiveness and acceptability of airway clearance in those treated with highly effective CFTR modulators., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)
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- 2023
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14. Improving Access to Renal Transplantation for Highly Sensitized Patients.
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Mason P and Robb ML
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- Humans, Histocompatibility Testing, Graft Survival, HLA Antigens, Kidney Transplantation
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Competing Interests: The authors declare no funding or conflicts of interest.
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- 2022
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15. Phenotypic continuum of NFU1-related disorders.
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Kaiyrzhanov R, Zaki MS, Lau T, Sen S, Azizimalamiri R, Zamani M, Sayin GY, Hilander T, Efthymiou S, Chelban V, Brown R, Thompson K, Scarano MI, Ganesh J, Koneev K, Gülaçar IM, Person R, Sadykova D, Maidyrov Y, Seifi T, Zadagali A, Bernard G, Allis K, Elloumi HZ, Lindy A, Taghiabadi E, Verma S, Logan R, Kirmse B, Bai R, Khalaf SM, Abdel-Hamid MS, Sedaghat A, Shariati G, Issa M, Zeighami J, Elbendary HM, Brown G, Taylor RW, Galehdari H, Gleeson JJ, Carroll CJ, Cowan JA, Moreno-De-Luca A, Houlden H, and Maroofian R
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- Humans, Phenotype, Mutation, Missense, Alleles, Iron metabolism, Carrier Proteins genetics, Spastic Paraplegia, Hereditary genetics
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Bi-allelic variants in Iron-Sulfur Cluster Scaffold (NFU1) have previously been associated with multiple mitochondrial dysfunctions syndrome 1 (MMDS1) characterized by early-onset rapidly fatal leukoencephalopathy. We report 19 affected individuals from 10 independent families with ultra-rare bi-allelic NFU1 missense variants associated with a spectrum of early-onset pure to complex hereditary spastic paraplegia (HSP) phenotype with a longer survival (16/19) on one end and neurodevelopmental delay with severe hypotonia (3/19) on the other. Reversible or irreversible neurological decompensation after a febrile illness was common in the cohort, and there were invariable white matter abnormalities on neuroimaging. The study suggests that MMDS1 and HSP could be the two ends of the NFU1-related phenotypic continuum., (© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
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- 2022
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16. CXD101 and nivolumab in patients with metastatic microsatellite-stable colorectal cancer (CAROSELL): a multicentre, open-label, single-arm, phase II trial.
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Saunders MP, Graham J, Cunningham D, Plummer R, Church D, Kerr R, Cook S, Zheng S, La Thangue N, and Kerr D
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- Humans, Microsatellite Repeats, Nivolumab pharmacology, Nivolumab therapeutic use, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics
- Abstract
Background: Patients with microsatellite stable (MSS) colorectal carcinoma (CRC) do not respond to immune checkpoint inhibitors. Preclinical models suggested synergistic anti-tumour activity combining CXD101 and anti-programmed cell death protein 1 treatment; therefore, we assessed the clinical combination of CXD101 and nivolumab in heavily pre-treated patients with MSS metastatic CRC (mCRC)., Patients and Methods: This single-arm, open-label study enrolled patients aged 18 years or older with biopsy-confirmed MSS CRC; at least two lines of systemic anticancer therapies (including oxaliplatin and irinotecan); at least one measurable lesion; Eastern Cooperative Oncology Group performance status of 0, 1 or 2; predicted life expectancy above 3 months; and adequate organ and bone marrow function. Nine patients were enrolled in a safety run-in study to define a tolerable combination schedule of CXD101 and nivolumab, followed by 46 patients in the efficacy assessment phase. Patients in the efficacy assessment cohort were treated orally with 20 mg CXD101 twice daily for 5 consecutive days every 3 weeks, and intravenously with 240 mg nivolumab every 2 weeks. The primary endpoint was immune disease control rate (iDCR)., Results: Between 2018 and 2020, 55 patients were treated with CXD101 and nivolumab. The combination therapy was well tolerated with the most frequent grade 3 or 4 adverse events being neutropenia (18%) and anaemia (7%). Immune-related adverse reactions commonly ascribed to checkpoint inhibitors were surprisingly rare although we did see single cases of pneumonitis, hypothyroidism and hypopituitarism. There were no treatment-related deaths. Of 46 patients assessable for efficacy, 4 (9%) achieved partial response and 18 (39%) achieved stable disease, translating to an immune disease control rate of 48%. The median overall survival (OS) was 7.0 months (95% confidence interval 5.13-10.22 months)., Conclusions: The primary endpoint was met in this phase II study, which showed that the combination of CXD101 and nivolumab, at full individual doses in the treatment of advanced or metastatic MSS CRC, was both well tolerated and efficacious., Competing Interests: Disclosure MS: Merck, Amgen, Servier. JG: Pierre Fabre, BMS, Bayer, Servier, Nucana, Amgen, MSD. DCu: OVIBIO and to To Royal Marsden Hospital: MedImmune/AZ, Clovis, Eli Lilly, 4SC, Bayer, Celgene, LEAP, Roche. RP: AZ, Novartis, Bayer, Tesaro, BMS, MSD, Pierre Fabre, Biosceptre, Cybrexa, Ellipses, Astex, CV6, Medivir, GammaDelta, Sanofi. DCh: MSD. RK: -. SC: Employee of Celleron and share options. SZ: Celleron share options. N. LaT: Celleron shares. DK: Personal Holdings and payments from Celleron + share options., (Copyright © 2022. Published by Elsevier Ltd.)
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- 2022
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17. Uterus Transplantation: A 50-Year Journey.
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Vali S, Jones BP, Saso S, Yazbek J, Quiroga I, and Smith JR
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- Animals, Female, Fertilization in Vitro, Humans, Pelvis, Tissue Donors, Uterus transplantation, Infertility, Female surgery
- Abstract
This paper provides an analysis of the last 50 years of uterus transplantation (UTx). Animal research on UTx began in the 1960s, aiming to solve tubal factor infertility. The success of in vitro fertilization shifted the focus onto uterine factor infertility. Early research in small and large animals improved following the advent of immunosuppression and established the uterus' ability to tolerate cold ischemia and to function following vessel reanastamosis. Upon the achievement of the first live birth following UTx in 2014, human research has started to focus on reducing donor morbidity, optimal immunosuppression regimes, and the development of deceased donor UTx programmes., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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18. Uterine Transplantation in 2021: Recent Developments and the Future.
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Jones BP, Kasaven LS, Chan M, Vali S, Saso S, Bracewell-Milnes T, Thum MY, Nicopoullos J, Diaz-Garcia C, Quiroga I, Yazbek J, and Smith JR
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- Female, Humans, Uterus surgery, Infertility, Female surgery
- Abstract
Uterine transplantation has evolved rapidly over the last decade. As the number of cases performed increases exponentially worldwide, emerging evidence continues to improve collective knowledge and understanding of the procedure, with the aim of improving both surgical and reproductive outcomes. Although currently restricted to women with absolute uterine factor infertility, increasing awareness as a method of fertility restoration has resulted in a demand for the procedure to be undertaken in transgender women. This manuscript summarizes the recent advances in uterine transplantation, and elaborates further upon the key novel avenues research within the field will focus on over the coming years., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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19. Provocation Testing and Therapeutic Response in a Newly Described Channelopathy: RyR2 Calcium Release Deficiency Syndrome.
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Ormerod JOM, Ormondroyd E, Li Y, Taylor J, Wei J, Guo W, Wang R, Sarton CNS, McGuire K, Dreau HMP, Taylor JC, Ginks MR, Rajappan K, Chen SRW, and Watkins H
- Subjects
- Animals, Arrhythmias, Cardiac complications, Calcium metabolism, Death, Sudden, Cardiac etiology, Flecainide, Humans, Metoprolol, Mice, Ryanodine Receptor Calcium Release Channel genetics, Channelopathies, Ryanodine Receptor Calcium Release Channel metabolism, Tachycardia, Ventricular genetics
- Abstract
Background: A novel familial arrhythmia syndrome, cardiac ryanodine receptor (RyR2) calcium release deficiency syndrome (CRDS), has recently been described. We evaluated a large and well characterized family to assess provocation testing, risk factor stratification and response to therapy in CRDS., Methods: We present a family with multiple unheralded sudden cardiac deaths and aborted cardiac arrests, primarily in children and young adults, with no clear phenotype on standard clinical testing., Results: Genetic analysis, including whole genome sequencing, firmly established that a missense mutation in RYR2 , Ala4142Thr, was the underlying cause of disease in the family. Functional study of the variant in a cell model showed RyR2 loss-of-function, indicating that the family was affected by CRDS. EPS (Electrophysiological Study) was undertaken in 9 subjects known to carry the mutation, including a survivor of aborted sudden cardiac death, and the effects of flecainide alone and in combination with metoprolol were tested. There was a clear gradation in inducibility of nonsustained and sustained ventricular arrhythmia between subjects at EPS, with the survivor of aborted sudden cardiac death being the most inducible subject. Administration of flecainide substantially reduced arrhythmia inducibility in this subject and abolished arrhythmia in all others. Finally, the effects of additional metoprolol were tested; it increased inducibility in 4/9 subjects., Conclusions: The Ala4142Thr mutation of RYR2 causes the novel heritable arrhythmia syndrome CRDS, which is characterized by familial sudden death in the absence of prior symptoms or a recognizable phenotype on ambulatory monitoring or exercise stress testing. We increase the experience of a specific EPS protocol in human subjects and show that it is helpful in establishing the clinical status of gene carriers, with potential utility for risk stratification. Our data provide evidence that flecainide is protective in human subjects with CRDS, consistent with the effect previously shown in a mouse model.
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- 2022
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20. Impaired pulmonary ventilation beyond pneumonia in COVID-19: A preliminary observation.
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Inui S, Yoon SH, Doganay O, Gleeson FV, and Kim M
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- COVID-19 diagnostic imaging, Female, Humans, Male, Middle Aged, Tomography, X-Ray Computed, COVID-19 pathology, Lung diagnostic imaging, Pulmonary Ventilation
- Abstract
Background: Coronavirus disease 2019 (COVID-19) may severely impair pulmonary function and cause hypoxia. However, the association of COVID-19 pneumonia on CT with impaired ventilation remains unexplained. This pilot study aims to demonstrate the relationship between the radiological findings on COVID-19 CT images and ventilation abnormalities simulated in a computational model linked to the patients' symptoms., Methods: Twenty-five patients with COVID-19 and four test-negative healthy controls who underwent a baseline non-enhanced CT scan: 7 dyspneic patients, 9 symptomatic patients without dyspnea, and 9 asymptomatic patients were included. A 2D U-Net-based CT segmentation software was used to quantify radiological futures of COVID-19 pneumonia. The CT image-based full-scale airway network (FAN) flow model was employed to assess regional lung ventilation. Functional and radiological features were compared across groups and correlated with the clinical symptoms. Heterogeneity in ventilation distribution and ventilation defects associated with the pneumonia and the patients' symptoms were assessed., Results: Median percentage ventilation defects were 0.2% for healthy controls, 0.7% for asymptomatic patients, 1.2% for symptomatic patients without dyspnea, and 11.3% for dyspneic patients. The median of percentage pneumonia was 13.2% for dyspneic patients and 0% for the other groups. Ventilation defects preferentially affected the posterior lung and worsened with increasing pneumonia linearly (y = 0.91x + 0.99, R2 = 0.73) except for one of the nine dyspneic patients who had disproportionally large ventilation defects (7.8% of the entire lung) despite mild pneumonia (1.2%). The symptomatic and dyspneic patients showed significantly right-skewed ventilation distributions (symptomatic without dyspnea: 0.86 ± 0.61, dyspnea 0.91 ± 0.79) compared to the patients without symptom (0.45 ± 0.35). The ventilation defect analysis with the FAN model provided a comparable diagnostic accuracy to the percentage pneumonia in identifying dyspneic patients (area under the receiver operating characteristic curve, 0.94 versus 0.96)., Conclusions: COVID-19 pneumonia segmentations from CT scans are accompanied by impaired pulmonary ventilation preferentially in dyspneic patients. Ventilation analysis with CT image-based computational modelling shows it is able to assess functional impairment in COVID-19 and potentially identify one of the aetiologies of hypoxia in patients with COVID-19 pneumonia., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Soon Ho Yoon works as a chief medical officer in MEDICALIP Co. Ltd. All other authors do not have a conflict of interest to declare associated with this publication. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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- 2022
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21. Mitochondrial Retinopathy.
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Birtel J, von Landenberg C, Gliem M, Gliem C, Reimann J, Kunz WS, Herrmann P, Betz C, Caswell R, Nesbitt V, Kornblum C, and Charbel Issa P
- Subjects
- Adolescent, Adult, Aged, Electroretinography, Female, Fundus Oculi, Humans, Male, Middle Aged, Retrospective Studies, Young Adult, Fluorescein Angiography methods, Mitochondrial Diseases diagnosis, Retinal Degeneration diagnosis, Retinal Pigment Epithelium pathology, Visual Acuity
- Abstract
Purpose: To report the retinal phenotype and the associated genetic and systemic findings in patients with mitochondrial disease., Design: Retrospective case series., Participants: Twenty-three patients with retinopathy and mitochondrial disease, including chronic progressive external ophthalmoplegia (CPEO), maternally inherited diabetes and deafness (MIDD), mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), Kearns-Sayre syndrome, neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome, and other systemic manifestations., Methods: Review of case notes, retinal imaging, electrophysiologic assessment, molecular genetic testing including protein modeling, and histologic analysis of muscle biopsy., Main Outcome Measures: Phenotypic characteristics of mitochondrial retinopathy., Results: Genetic testing identified sporadic large-scale mitochondrial DNA deletions and variants in MT-TL1, MT-ATP6, MT-TK, MT-RNR1, or RRM2B. Based on retinal imaging, 3 phenotypes could be differentiated: type 1 with mild, focal pigmentary abnormalities; type 2 characterized by multifocal white-yellowish subretinal deposits and pigment changes limited to the posterior pole; and type 3 with widespread granular pigment alterations. Advanced type 2 and 3 retinopathy presented with chorioretinal atrophy that typically started in the peripapillary and paracentral areas with foveal sparing. Two patients exhibited a different phenotype: 1 revealed an occult retinopathy, and the patient with RRM2B-associated retinopathy showed no foveal sparing, no severe peripapillary involvement, and substantial photoreceptor atrophy before loss of the retinal pigment epithelium. Two patients with type 1 disease showed additional characteristics of mild macular telangiectasia type 2. Patients with type 1 and mild type 2 or 3 disease demonstrated good visual acuity and no symptoms associated with the retinopathy. In contrast, patients with advanced type 2 or 3 disease often reported vision problems in dim light conditions, reduced visual acuity, or both. Short-wavelength autofluorescence usually revealed a distinct pattern, and near-infrared autofluorescence may be severely reduced in type 3 disease. The retinal phenotype was key to suspecting mitochondrial disease in 11 patients, whereas 12 patients were diagnosed before retinal examination., Conclusions: Different types of mitochondrial retinopathy show characteristic features. Even in absence of visual symptoms, their recognition may facilitate the often challenging and delayed diagnosis of mitochondrial disease, in particular in patients with mild or nebulous multisystem disease., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
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- 2022
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22. Partial Breast Reconstruction with Lateral Chest Wall Perforator Flap to Facilitate Breast Conservation in Breast Cancer: First 100 Cases with Cancer Outcomes at 8 Years Follow-Up and the Lessons Learned.
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Roy PG, Mustata L, Hu J, Phillips B, Parulekar V, Bhattacharyya M, Harris A, and Oliveros S
- Abstract
Background: This is a prospective cohort study of partial breast reconstruction (PBR) with a lateral chest wall perforator flap (LCWPF) to facilitate breast conservation surgery (BCS) for women undergoing surgery for breast cancer. The study was undertaken to study the clinical and cancer outcomes., Methods: Patients diagnosed with ductal carcinoma in situ (DCIS) or breast cancer who consented to undergo BCS with PBR with LCWPF were included in the study. A prospective database has been maintained to collect information on clinico-pathological features, complications, and follow-up. Patients were asked to complete an anonymised PROM questionnaire over the years. The hospital electronic records were interrogated for women who have completed 5 years follow-up to assess for development of recurrence/events., Results: A total of 105 patients underwent PBR with LCWPFs between 2011 and 2018. Of these, 74% underwent cancer resection and PBR as one operation whilst 26% underwent PBR as a two-stage approach. The median tumor size on pre-op imaging was 30 mm for the one-stage approach and 39.5 mm for the two-stage approach ( p -value=0.003). The complication rates were low and the re-operation rate for close margins was 10%, with 4% eventually requiring mastectomy. Good-to-excellent esthetic outcomes were reported in more than 80% of cases by patients and clinicians. The local recurrence rate (LR) was 2%, distant recurrence rate 10.5%, disease free survival (DFS) 86%, distant disease-free survival (DDFS) 89% and overall survival (OS) 94.8% at 4.5 years median follow-up. This procedure provides an effective oncological approach, avoiding mastectomy with a good-to-excellent cosmetic outcome. The follow-up data establishes the safety of this approach., Discussion: This is the first published series of recurrence and survival data in patients undergoing PBR. We intend to continue with data collection to assess long-term outcomes beyond 10 years. The authors would recommend consideration of this technique to facilitate BCS and avoid mastectomy., Registration: Not applicable., Competing Interests: The authors report no conflicts of interest for this work., (© 2021 Roy et al.)
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- 2021
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23. Fitness enhances psychosocial well-being and self-confidence in young men with hemophilia: Results from Project GYM.
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Khair K, Holland M, Dodgson S, McLaughlin P, Fletcher S, and Christie D
- Abstract
Introduction: Contemporary hemophilia care supports physical activity, its benefits being well recognized. Despite recognition of the psychological challenges encountered by people with hemophilia, little is known about the psychological impact of physical fitness in this population., Aim: To identify changes in psychological well-being in young men with hemophilia through participation in a gym program., Methods: This observational feasibility study of a 6-month gym participation program used validated questionnaires pre- and poststudy to evaluate motivation to exercise, physical activity levels, self-efficacy, self-esteem, and quality of life. Individual audio-recorded interviews about study participation and impact were transcribed verbatim and analyzed for recurring themes using thematic analysis., Results: Nineteen participants aged 18-25 years with hemophilia A or B (all severities ± inhibitor) consented to the study; two were lost to follow-up. There was a shift in motivation to exercise as shown by the Stages of Change grouping moving from contemplation to action and maintenance phases ( p = 0.03). Self-efficacy overall scores showed a trend ( p < 0.06) towards improvement. Median self-esteem scores improved from 22 (range 12-30, n = 19) to 25 (range 13-30, n = 17), a statistically significant change ( p = 0.02). Three participants recorded scores below the accepted normal range before study, of whom two improved at study end. The key themes identified from the interviews were: fear, self-confidence, "being normal," pain, weight loss, ability, getting fitter., Conclusions: The psychological wellbeing of young men with hemophilia improved during this study. This may have been related to participating in a gym-based, physical exercise program., (© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)
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- 2021
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24. Frequency drift in MR spectroscopy at 3T.
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Hui SCN, Mikkelsen M, Zöllner HJ, Ahluwalia V, Alcauter S, Baltusis L, Barany DA, Barlow LR, Becker R, Berman JI, Berrington A, Bhattacharyya PK, Blicher JU, Bogner W, Brown MS, Calhoun VD, Castillo R, Cecil KM, Choi YB, Chu WCW, Clarke WT, Craven AR, Cuypers K, Dacko M, de la Fuente-Sandoval C, Desmond P, Domagalik A, Dumont J, Duncan NW, Dydak U, Dyke K, Edmondson DA, Ende G, Ersland L, Evans CJ, Fermin ASR, Ferretti A, Fillmer A, Gong T, Greenhouse I, Grist JT, Gu M, Harris AD, Hat K, Heba S, Heckova E, Hegarty JP 2nd, Heise KF, Honda S, Jacobson A, Jansen JFA, Jenkins CW, Johnston SJ, Juchem C, Kangarlu A, Kerr AB, Landheer K, Lange T, Lee P, Levendovszky SR, Limperopoulos C, Liu F, Lloyd W, Lythgoe DJ, Machizawa MG, MacMillan EL, Maddock RJ, Manzhurtsev AV, Martinez-Gudino ML, Miller JJ, Mirzakhanian H, Moreno-Ortega M, Mullins PG, Nakajima S, Near J, Noeske R, Nordhøy W, Oeltzschner G, Osorio-Duran R, Otaduy MCG, Pasaye EH, Peeters R, Peltier SJ, Pilatus U, Polomac N, Porges EC, Pradhan S, Prisciandaro JJ, Puts NA, Rae CD, Reyes-Madrigal F, Roberts TPL, Robertson CE, Rosenberg JT, Rotaru DG, O'Gorman Tuura RL, Saleh MG, Sandberg K, Sangill R, Schembri K, Schrantee A, Semenova NA, Singel D, Sitnikov R, Smith J, Song Y, Stark C, Stoffers D, Swinnen SP, Tain R, Tanase C, Tapper S, Tegenthoff M, Thiel T, Thioux M, Truong P, van Dijk P, Vella N, Vidyasagar R, Vovk A, Wang G, Westlye LT, Wilbur TK, Willoughby WR, Wilson M, Wittsack HJ, Woods AJ, Wu YC, Xu J, Lopez MY, Yeung DKW, Zhao Q, Zhou X, Zupan G, and Edden RAE
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- Humans, Magnetic Resonance Imaging methods, Magnetic Resonance Spectroscopy methods, Brain diagnostic imaging, Brain metabolism, Data Analysis, Databases, Factual standards, Magnetic Resonance Imaging standards, Magnetic Resonance Spectroscopy standards
- Abstract
Purpose: Heating of gradient coils and passive shim components is a common cause of instability in the B
0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites., Method: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC)., Results: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI., Discussion: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed., Competing Interests: Declaration of Competing Interest Jack J. Miller would like to acknowledge the support of a Novo Nordisk Research Fellowship run in conjunction with the University of Oxford. Francisco Reyes-Madrigal has served as a speaker for Janssen (Johnson & Johnson) and AstraZeneca. Marc Thioux and Pim van Dijk were supported by The Netherlands Organization for Health Research and Development (ZonMW) and the Dorhout Mees Foundation. All other authors have no conflict of interest to declare., (Copyright © 2021. Published by Elsevier Inc.)- Published
- 2021
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25. Efficacy and safety of the EMS Swiss LithoClast® Trilogy for PCNL: results of the European multicentre prospective study on behalf of European Section of UroTechnology.
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Thakare N, Tanase F, Saeb-Parsy K, Atassi N, Endriss R, Kamphuis G, Pérez-Fentes D, Hasan M, Brehmer M, Osther P, Jung H, Turney B, Finch W, Burgess N, Irving S, Dragos L, Liatsikos E, Knoll T, Cauni V, and Wiseman O
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Equipment Design, Female, Humans, Male, Middle Aged, Prospective Studies, Treatment Outcome, Young Adult, Kidney Calculi surgery, Nephrolithotomy, Percutaneous instrumentation
- Abstract
Purpose: PCNL requires a lithotrite to efficiently break stones, and some devices include active suction to remove the fragments. We set out to determine the efficacy and safety of the Swiss LithoClast® Trilogy, in a prospective European multicentre evaluation and compared it to published stone clearance rates for Trilogy based on surface area (68.9 mm
2 /min) and using the 3D calculated stone volume (526.7 mm3 /min)., Methods: Ten European centres participated in this prospective non-randomized study of Trilogy for PCNL. Objective measures of stone clearance rate, device malfunction, complications and stone-free rates were assessed. Each surgeon subjectively evaluated ergonomic and device effectiveness, on a 1-10 scale (10 = extremely ergonomic/effective) and compared to their usual lithotrite on a 1-10 scale (10 = extremely effective)., Results: One hundred and fifty seven PCNLs using Trilogy were included (53% male, 47% female; mean age 55 years, range 13-84 years). Mean stone clearance rate was 65.55 mm2 /min or 945 mm3 /min based on calculated 3D volume. Stone-free rate on fluoroscopy screening at the end of the procedure was 83%. Feedback for suction effectiveness was 9.0 with 9.1 for combination and 9.0 for overall effectiveness compared to lithotrite used previously. Ergonomic score was 8.1, the least satisfactory element. Complications included 13 (8.2%) Clavien-Dindo Grade II and 2 (1.3%) Grade III. Probe breakage was seen in 9 (5.7%), none required using a different lithotrite., Conclusions: We have demonstrated that Trilogy is highly effective at stone removal. From a user perspective, the device was perceived by surgeons to be highly effective overall and compared to the most commonly used previous lithotrite, with an excellent safety profile., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2021
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26. Hyperpolarized 129 Xe MRI Abnormalities in Dyspneic Patients 3 Months after COVID-19 Pneumonia: Preliminary Results.
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Grist JT, Chen M, Collier GJ, Raman B, Abueid G, McIntyre A, Matthews V, Fraser E, Ho LP, Wild JM, and Gleeson F
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- Adult, Aged, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prospective Studies, SARS-CoV-2, COVID-19 physiopathology, Dyspnea physiopathology, Lung diagnostic imaging, Lung physiopathology, Magnetic Resonance Imaging methods, Xenon Isotopes
- Abstract
Background SARS-CoV-2 targets angiotensin-converting enzyme 2-expressing cells in the respiratory tract. There are reports of breathlessness in patients many months after infection. Purpose To determine whether hyperpolarized xenon 129 MRI (XeMRI) imaging could be used to identify the possible cause of breathlessness in patients at 3 months after hospital discharge following COVID-19 infection. Materials and Methods This prospective study was undertaken between August and December of 2020, with patients and healthy control volunteers being enrolled. All patients underwent lung function tests; ventilation and dissolved-phase XeMRI, with the mean red blood cell (RBC) to tissue or plasma (TP) ratio being calculated; and a low-dose chest CT, with scans being scored for the degree of abnormalities after COVID-19. Healthy control volunteers underwent XeMRI. The intraclass correlation coefficient was calculated for volunteer and patient scans to assess repeatability. A Wilcoxon rank sum test and Cohen effect size calculation were performed to assess differences in the RBC/TP ratio between patients and control volunteers. Results Nine patients (mean age, 57 years ± 7 [standard deviation]; six male patients) and five volunteers (mean age, 29 years ± 3; five female volunteers) were enrolled. The mean time from hospital discharge for patients was 169 days (range, 116-254 days). There was a difference in the RBC/TP ratio between patients and control volunteers (0.3 ± 0.1 vs 0.5 ± 0.1, respectively; P = .001; effect size, 1.36). There was significant difference between the RBC and gas phase spectral full width at half maximum between volunteers and patients (median ± range, 567 ± 1 vs 507 ± 81 [ P = .002] and 104 ± 2 vs 122 ± 17 [ P = .004], respectively). Results were reproducible, with intraclass correlation coefficients of 0.82 and 0.88 being demonstrated for patients and volunteers, respectively. Participants had normal or nearly normal CT scans (mean, seven of 25; range, zero of 25 to 10 of 25). Conclusion Hyperpolarized xenon 129 MRI results showed alveolar capillary diffusion limitation in all nine patients after COVID-19 pneumonia, despite normal or nearly normal results at CT. © RSNA, 2021 See also the editorial by Dietrich in this issue.
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- 2021
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