Hoffmikkelsen0830

Funnel plot analysis identified 4 high-performers for frequent dietitian assessments (range 92% - 98%) and 4 under-performers (range 17% - 56%). High-performers treated inadequate weight gain more often with adequate calories (24/30, 80% v. 12/23, 52%) and closer follow up (104/164, 63% v. 60/120, 49%) compared to under-performers. Three of 4 high-performing sites met center nutrition goals for positive median WAZ at 2 years old unlike 3 under-performers (WAZ

0.33 v. WAZ

-0.15), despite similar patient characteristics.

We characterized multicenter variation in dietitian assessments, identifying opportunities to improve care delivery to target early nutrition outcomes.

We characterized multicenter variation in dietitian assessments, identifying opportunities to improve care delivery to target early nutrition outcomes.Maple syrup urine disease (MSUD) is a rare, inherited metabolic disorder characterized by a dysfunctional mitochondrial enzyme complex, branched-chain alpha-keto acid dehydrogenase (BCKDH), which catabolizes branched-chain amino acids (BCAAs). Without functional BCKDH, BCAAs and their neurotoxic alpha-keto intermediates can accumulate in the blood and tissues. MSUD is currently incurable and treatment is limited to dietary restriction or liver transplantation, meaning there is a great need to develop new treatments for MSUD. We evaluated potential gene therapy applications for MSUD in the intermediate MSUD (iMSUD) mouse model, which harbors a mutation in the dihydrolipoamide branched-chain transacylase E2 (DBT) subunit of BCKDH. Systemic delivery of an adeno-associated virus (AAV) vector expressing DBT under control of the liver-specific TBG promoter to the liver did not sufficiently ameliorate all aspects of the disease phenotype. These findings necessitated an alternative therapeutic strategy. Muscle makes a larger contribution to BCAA metabolism than liver in humans, but a muscle-specific approach involving a muscle-specific promoter for DBT expression delivered via intramuscular (IM) administration only partially rescued the MSUD phenotype in mice. Combining the muscle-tropic AAV9 capsid with the ubiquitous CB7 promoter via IM or IV injection, however, substantially increased survival across all assessed doses. Additionally, near-normal serum BCAA levels were achieved and maintained in the mid- and high-dose cohorts throughout the study; this approach also protected these mice from a lethal high-protein diet challenge. Therefore, administration of a gene therapy vector that expresses in both muscle and liver may represent a viable approach to treating patients with MSUD.

Obesity and type 2 diabetes have been associated with an increased risk of kidney stones in observational studies, but the causality of these associations remains unestablished. We conducted a Mendelian randomization study to determine these associations.

Independent single nucleotide polymorphisms at the genome-wide significance threshold (p<5×10

) were selected as instrumental variables and were identified from meta-analyses of genome-wide association studies on body mass index (up to 806,834 individuals) and type 2 diabetes (228,499 cases and 1,178,783 non-cases). Summary-level data for the associations of exposure-associated SNPs with kidney stones were obtained from the UK Biobank study (3540 cases and 357,654 non-cases) and the FinnGen consortium (3856 cases and 172,757 non-cases). Causal estimates from two sources were combined using the meta-analysis method.

Higher genetically predicted body mass index and genetic liability to type 2 diabetes were associated with an increased risk of kidney stones in both the UK Biobank study and FinnGen consortium. NX-2127 In the meta-analysis of results from the two data sources, the odds ratios of kidney stones were 1.33 (95% confidence interval, 1.17, 1.51; p<0.001) per one standard deviation increase in genetically predicted body mass index (~4.8kg/m

) and 1.15 (95% confidence interval, 1.10, 1.20; p<0.001) for one unit increase in genetically predicted log-transformed odds of type 2 diabetes.

This study based on genetic data suggests that a high body mass index and type 2 diabetes may be causal risk factors for kidney stone formation.

This study based on genetic data suggests that a high body mass index and type 2 diabetes may be causal risk factors for kidney stone formation.

The cryopreservation of hematopoietic stem cells (HSCs) in dimethyl sulfoxide (DMSO) is used widely, but DMSO toxicity in transplant patients and the effects of DMSO on the normal function of cryopreserved cells are concerns. To address these issues, in vitro and clinical studies have explored using reduced concentrations of DMSO for cryopreservation. However, the effect of reducing DMSO concentration on the efficient cryopreservation of HSCs has not been directly measured.

Cryopreservation of human bone marrow using 10%, 7.5% and 5% DMSO concentrations was examined. Cell counting, flow cytometry and colony assays were used to analyze different cell populations. The recovery of stem cells was enumerated using extreme limiting dilution analysis of long-term multi-lineage engraftment in immunodeficient mice. Four different methods of analyzing human engraftment were compared to ascertain stem cell engraftment (i) engraftment of CD33

myeloid, CD19

B-lymphoid, CD235a

erythroid and CD34

progenitors; (ii) engraftment of the same four populations plus CD41

CD42b

platelets; (iii) engraftment of CD34

CD133

cells; and (iv) engraftment of CD34

CD38

cells.

Hematopoietic colony-forming, CD34

, CD34

CD133

and CD34

CD38

cells were as well preserved with 5% DMSO as they were with the higher concentrations tested. The estimates of stem cell frequencies made in the xenogeneic transplant model did not show any significant detrimental effect of using lower concentrations of DMSO. Comparison of the different methods of gauging stem cell engraftment in mice led to different estimates of stem cell numbers, but overall, all measures found that reduced concentrations of DMSO supported the cryopreservation of HSCs.

Cryopreservation of HSCs in DMSO concentrations as low as 5% is effective.

Cryopreservation of HSCs in DMSO concentrations as low as 5% is effective.

To analyse the outcomes of retroperitoneoscopic upper and lower moiety hemi-nephroureterectomy (HNU) and to assess the different variables that may have an impact on outcome; remnant moiety damage, morbidity and the need for secondary surgery.

Prospectively recorded data of retroperitoneoscopic HNU's performed by a single surgeon from 2005 to 2018 were analysed. Patients were split into 2 groups according to moiety affected (UMHNU and LMHNU). Clinical presentation, underlying pathology, remnant moiety DRF on renal scintigraphy, and need for further surgery were recorded. Detailed operation notes were studied regards to renal vasculature, degree of dilatation, inflammatory changes and operative difficulties encountered. Renal loss was defined as remnant moiety DRF <10% post-operatively. Change in DRF was assessed regards to the moiety, pathology and age at surgery (<1 year, 1-2 years and ≥2 years). UMHNU group was further sub-divided into 3 subgroups ureteroceles, ectopic ureters and 'other' pathologatients. Age <1year was also related to increased renal loss (2/8 patients <1 year, 1/25 patients 1-2 years, 1/45 patients ≥2 years of age P=0.005).

Retroperitoneoscopic LMHNU is a safe and definitive procedure with rapid recovery and minimal scarring. UMHNU has higher rates of remnant moiety loss due to more complex renal pathology, but remains a safe, successful operation on the majority of patients. Renal damage was also related to age <1year (p=0.005) and re-operation risk after UMHNU correlated to the presence of ureterocele (p=0.003).

Retroperitoneoscopic LMHNU is a safe and definitive procedure with rapid recovery and minimal scarring. UMHNU has higher rates of remnant moiety loss due to more complex renal pathology, but remains a safe, successful operation on the majority of patients. Renal damage was also related to age less then 1year (p = 0.005) and re-operation risk after UMHNU correlated to the presence of ureterocele (p = 0.003).

Moderate hypofractionated radiotherapy has become routine practice for a selected population of patients treated for early-stage breast cancer. In April 2020, the Fast Forward (FF) study was published which introduced another extreme hypofractionated radiotherapy regimen in five sessions over a week. The aim of this work is to evaluate the population of first patients in whom this regimen was used in our department, as well as the results in terms of early toxicity.

We retrospectively analysed all the patients treated in our department according to the Fast Forward protocol after establishing an institutional consensus regarding the selection of patients with breast cancer without indication for lymph node irradiation. All patients received breast-only irradiation at a total dose of 26Gy in five fractions according to protocol. All patients were treated by modern conformational techniques with planning large volume coverage between 95 and 100%. Acute toxicity of the treatment was assessed using the NCI CTording to the Fast Forward protocol on the breast alone with adapted techniques show that the protocol is feasible, with little early toxicity but a greater follow-up is necessary to assess long-term toxicity.

The results of this series of patients treated with hypofractionated radiotherapy according to the Fast Forward protocol on the breast alone with adapted techniques show that the protocol is feasible, with little early toxicity but a greater follow-up is necessary to assess long-term toxicity.Stereotactic radiotherapy is used for patients with oligometastases from colorectal cancer. It results in good local tumour control, especially for hepatic and pulmonary metastases, subject to a sufficiently high biologically effective dose, and is well-tolerated. It can be associated with other local treatments such as surgery or radiofrequency as part of combined treatments, in order to increase patient survival.

Implementation of Artificial Intelligence (AI) into medical imaging is much debated. Diagnostic Radiographers (DRs) and Radiation Therapists (RTTs) are at the forefront of this technological leap, thus an understanding of their views, in particular changes to their current roles, is key to safe, optimal implementation.

An online survey was designed, including themes role changes, clinical priorities for AI, patient benefits, and education. It was distributed nationally in the Republic of Ireland via the national professional body, clinical management, and social media.

318 DRs and 77 RTTs participated. Priority areas for development included quality assurance, clinical audit, radiation dose optimisation, and improved workflow for DRs and treatment planning algorithm optimisation, clinical audit, and post processing for RTTs. There was resistance regarding AI use for patient facing roles and final image interpretation. 27.6% of DRs and 40.3% of RTTs currently use AI clinically and 46.1% of DRs and 41.2% of RTTs anticipate reduced staffing levels with AI.