Assessment of the healing of conservatively-treated scaphoid fractures using HR-pQCT.

Improving the clinical outcome of scaphoid fractures may benefit from adequate monitoring of their healing in order to for example identify complications such as scaphoid nonunion at an early stage and to adjust the treatment strategy accordingly. However, quantitative assessment of the healing process is limited with current imaging modalities. In this study, high-resolution peripheral quantitative computed tomography (HR-pQCT) was used for the first time to assess the changes in bone density, microarchitecture, and strength during the healing of conservatively-treated scaphoid fractures. Thirteen patients with a scaphoid fracture (all confirmed on HR-pQCT and eleven on CT) received an HR-pQCT scan at baseline and three, six, twelve, and 26 weeks after first presentation at the emergency department. Bone mineral density (BMD) and trabecular microarchitecture of the scaphoid bone were quantified, and failure load (FL) was estimated using micro-finite element analysis. Longitudinal changes were evaluated with linear mixed-effects models. Data of two patients were excluded due to surgical intervention after the twelve-week follow-up visit. In the eleven fully evaluable patients, the fracture line became more apparent at 3 weeks. At 6 weeks, individual trabeculae at the fracture region became more difficult to identify and distinguish from neighboring trabeculae, and this phenomenon concerned a larger region around the fracture line at 12 weeks. Quantitative assessment showed that BMD and FL were significantly lower than baseline at all follow-up visits with the largest change from baseline at 6 weeks (-13.6% and - 23.7%, respectively). BMD remained unchanged thereafter, while FL increased. Trabecular thickness decreased significantly from baseline at three (-3.9%), six (-6.7%), and twelve (-4.4%) weeks and trabecular number at six (-4.5%), twelve (-7.3%), and 26 (-7.9%) weeks. Trabecular separation was significantly higher than baseline at six (+13.3%), twelve (+19.7%), and 26 (+16.3%) weeks. To conclude, this explorative HR-pQCT study showed a substantial decrease in scaphoid BMD, Tb.Th, and FL during the first 6 weeks of healing of conservatively-treated scaphoid fractures, followed by stabilization or increase in these parameters. At 26 weeks, BMD, trabecular microarchitecture, and FL were not returned to baseline values.

Advanced Molecular Characterization Using Digital Spatial Profiling Technology on Immunooncology Targets in Methylated Compared with Unmethylated IDH-Wildtype Glioblastoma.

INTRODUCTION: Glioblastoma (GBM) is the most common primary adult brain tumour with a median overall survival (OS) of 12-15 months. Molecular characterization of multiple immunooncology targets in GBM may help target novel immunotherapeutic strategies. We used NanoString GeoMx® Digital Spatial Profiling (DSP) to assess multiple immunooncology protein targets in methylated versus unmethylated IDH-wild-type glioblastoma. METHODS: NanoString GeoMx® DSP technology uses multiple primary antibodies conjugated to indexing DNA oligos with a UV photocleavable linker. Tissue regions of interest (ROIs) are selected with bound fluorescent antibodies; oligos are released via a UV-mediated linker and quantitated. We used DSP multiplex analysis of 31 immunooncology proteins and controls (CD4, CD14, CD68, CD8A, B7-H3, PD-L1, CD19, FOXP3, CD44, STAT3 (phospho Y705), CD45, Pan Cytokeratin, MS4A1/CD20, CD45RO, PD1, CD3, beta-2 microglobulin, VISTA, Bcl2, GZMB, PTEN, beta-catenin, CD56, Ki-67, STAT3, AKT, p-Akt, S6, Histone H3, IgG Rabbit control, and Mouse IgG control) from ROIs in a cohort of 10 IDH-wild-type glioblastomas (5 methylated and 5 unmethylated). An nCounter platform allowed quantitative comparisons of antibodies between ROIs in MGMT methylated and unmethylated tumours. Mean protein expression counts between methylated and unmethylated GBM were compared using technical and biological replicates. RESULTS: The analysis showed 10/27 immunooncology target proteins were significantly increased in methylated versus unmethylated IDH-wild-type glioblastoma tumour core (false discovery rate (FDR) <0.1 by Benjamini-Hochberg procedure). CONCLUSIONS: NanoString GeoMx® DSP was used to analyse multiple immunooncology protein target expression in methylated versus unmethylated IDH-wild-type glioblastoma. In this small study, there was a statistical increase in CD4, CD14, CD68, CD8A, B7-H3, PDL-1, CD19, FOXP3, CD44, and STAT3 protein expression in methylated versus unmethylated GBM tumour core; however, this requires larger cohort validation. Advanced multiplex immunooncological biomarker analysis may be useful in identifying biomarkers for novel immunotherapeutic agents in GBMs.

Examining the reliability of ICD-10 discharge coding in Red Cross War Memorial Children's Hospital administrative database.

BACKGROUND: Discharge diagnostic data from hospital administrative databases are often used to inform decisions relating to a variety of vital applications. These may include the allocation of resources, quality-of-care assessments, clinical research and formulation of healthcare policy. Accurately coded and reliably captured patient discharge data are of paramount importance for any hospital and health system to function efficiently. OBJECTIVES: To retrospectively examine the reliability of the International Classification of Diseases version 10 (ICD-10) discharge coding in Red Cross War Memorial Children's Hospital (RCWMCH)'s administrative database for primary and secondary discharge diagnoses, and to formulate recommendations for improvement to the current system. METHODS: This study was a retrospective folder review of 450 patient admissions to the short-stay and general paediatric wards at RCWMCH between 1 August 2013 and 1 September 2014. The principal investigator (PI) completed ICD-10 discharge coding for each admission and compared it with the corresponding admission data captured for each patient in the Clinicom (Siemens Medical Solutions, Germany) health information system. Agreement comparison was done to 4- and 3-character ICD-10 code specificity. RESULTS: Of the initial 450 randomly selected folders, 396 (88%) were analysed during the folder review process. The median number of total diagnoses (primary diagnosis plus secondary diagnoses) coded by the PI folder review was 3, with a distribution of 1 - 10 (interquartile range (IQR) 2 - 4). The median number of total diagnoses coded in Clinicom was 1, with a distribution of 1 - 3 (IQR 1 - 1). Agreement of primary diagnosis coding to 4 characters was 26.3%, with slight improvement to 34.3% when assessed to 3 characters. Agreement of secondary diagnoses to 4 characters was 14.9%, and 27.7% when assessed to 3 characters. CONCLUSIONS: Reliability of administrative ICD-10 discharge data from RCWMCH is poor. Inadequacies regarding the employment of dedicated and/or adequately trained coding personnel may significantly contribute to the problem and should be addressed.

Association of secondary displacement of distal radius fractures with cortical bone quality at the distal radius.

INTRODUCTION: The aim of this study was to investigate the associations of patient characteristics, bone mineral density (BMD), bone microarchitecture and calculated bone strength with secondary displacement of a DRF based on radiographic alignment parameters. MATERIALS AND METHODS: Dorsal angulation, radial inclination and ulnar variance were assessed on conventional radiographs of a cohort of 251 patients, 38 men and 213 women, to determine the anatomic position of the DRF at presentation (primary position) and during follow-up. Secondary fracture displacement was assessed in the non-operatively treated patients (N = 154) with an acceptable position, preceded (N = 97) or not preceded (N = 57) by primary reduction (baseline position). Additionally, bone microarchitecture and calculated bone strength at the contralateral distal radius and tibia were assessed by HR-pQCT in a subset of, respectively, 63 and 71 patients. OUTCOME: Characteristics of patients with and without secondary fracture displacement did not differ. In the model with adjustment for primary reduction [OR 22.00 (2.27-212.86), p = 0.008], total [OR 0.16 (95% CI 0.04-0.68), p = 0.013] and cortical [OR 0.19 (95% CI 0.05-0.80], p = 0.024] volumetric BMD (vBMD) and cortical thickness [OR 0.13 (95% CI 0.02-0.74), p = 0.021] at the distal radius were associated with secondary DRF displacement. No associations were found for other patient characteristics, such as age gender, BMD or prevalent vertebral fractures. CONCLUSIONS: In conclusion, our study indicates that besides primary reduction, cortical bone quality may be important for the risk of secondary displacement of DRFs.

Improved Detection of Scaphoid Fractures with High-Resolution Peripheral Quantitative CT Compared with Conventional CT.

BACKGROUND: Computed tomography (CT), magnetic resonance imaging, and bone scintigraphy are second-line imaging techniques that are frequently used for the evaluation of patients with a clinically suspected scaphoid fracture. However, as a result of varying diagnostic performance results, no true reference standard exists for scaphoid fracture diagnosis. We hypothesized that the use of high-resolution peripheral quantitative CT (HR-pQCT) in patients with a clinically suspected scaphoid fracture could improve scaphoid fracture detection compared with conventional CT in the clinical setting. METHODS: The present study included 91 consecutive patients (≥18 years of age) who presented to the emergency department with a clinically suspected scaphoid fracture between December 2017 and October 2018. All patients were clinically reassessed within 14 days after first presentation, followed by CT and HR-pQCT. If a scaphoid fracture was present, the fracture type was determined according to the Herbert classification system and correlation between CT and HR-pQCT was estimated with use of the Kendall W statistic or coefficient of concordance (W) (the closer to 1, the higher the correlation). RESULTS: The cohort included 45 men and 46 women with a median age of 52 years (interquartile range, 29 to 67 years). HR-pQCT revealed a scaphoid fracture in 24 patients (26%), whereas CT revealed a scaphoid fracture in 15 patients (16%). Patients with a scaphoid fracture were younger and more often male. The correlation between CT and HR-pQCT was high for scaphoid fracture type according to the Herbert classification system (W = 0.793; 95% confidence interval [CI], 0.57 to 0.91; p < 0.001) and very high for scaphoid fracture location (W = 0.955; 95%, CI 0.90 to 0.98; p < 0.001). CONCLUSIONS: In the present study, the number of patients diagnosed with a scaphoid fracture was 60% higher when using HR-pQCT as compared with CT. These findings imply that a substantial proportion of fractures-in this study, more than one-third-will be missed by the current application of CT scanning in patients with a clinically suspected scaphoid fracture. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Is pre-operative heart rate variability a prognostic indicator for overall survival and cancer recurrence in patients with primary colorectal cancer?

BACKGROUND: Heart Rate Variability (HRV) represents efferent vagus nerve activity which is suggested to be inversely related to fundamental mechanisms of tumorigenesis and to be a predictor of prognosis in various types of cancer. HRV is also believed to predict the occurrence and severity of post-operative complications. We aimed to determine the role of pre-operative HRV as a prognostic factor in overall and cancer free survival in patients with colorectal cancer. METHODS: Retrospective analysis was performed in a detailed dataset of patients diagnosed with primary colorectal cancer between January 2010 and December 2016, who underwent curative surgical treatment. HRV was measured as time-domain parameters (SDNN (Standard Deviation of NN-intervals) and RMSSD (Root Mean Square of Successive Differences)) based on pre-operative 10 second ECGs. Groups were created by baseline HRV: Low HRV (SDNN <20ms or RMSSD <19ms) and normal HRV (SDNN ≥20ms or RMSSD ≥19ms). Primary endpoints were overall and cancer free survival. RESULTS: A total of 428 patients were included in this study. HRV was not significantly associated with overall survival (SDNN <20ms vs SDNN ≥20ms:24.4% vs 22.8%, adjusted HR = 0.952 (0.607-1.493), p = 0.829; RMSSD <19ms vs RMSSD ≥19ms:27.0% vs 19.5%, adjusted HR = 1.321 (0.802-2.178), p = 0.274) or cancer recurrence (SDNN <20ms vs ≥20ms:20.1% vs 18.7%, adjusted HR = 0.976 (0.599-1.592), p = 0.924; RMSSD <19ms vs ≥19ms, 21.5% vs 16.9%, adjusted HR = 1.192 (0.706-2.011), p = 0.511). There was no significant association between HRV and CEA-level at one year follow-up, or between HRV and occurrence of a post-operative complication or the severity of post-operative complications. CONCLUSIONS: Heart rate variability was not associated with overall or cancer free survival in patients with primary colorectal cancer who underwent curative surgical treatment. These results do not align with results found in studies including only patients with advanced cancer, which suggests that there is only an association in the other direction, cancer causing low HRV.

The Early Impact of COVID-19 on Urological Service Provision.

Aim COVID-19 has posed an unprecedented challenge to healthcare systems. We aimed to observe the impact on urological care delivery in an Irish university hospital. Methods Data on urological activity was prospectively collected for 3 months from March 2020. A retrospective review of the same period in 2019 was performed for control data. Results Over the 2020 study period, 356 urological admissions were recorded; a 23.1% decrease from the 2019 corresponding period(n=463). A 21.7% decrease in flexible cystoscopies was seen (162 versus 207). 125 theatre cases (36 off-site) were performed in the 2020 period, versus 151 in 2019. Emergency case load remained stable, with 69 cases in the 2020 period. The percentage of trainee-performed cases was preserved. COVID-era outpatient activity increased, to involve 559 clinic consultations compared to 439 the preceding year; a reflection of annual growth in service demand and facilitated by virtual clinic application (n=403). There were 490 instances of patients cancelling/failing to attend outpatient appointments, compared to 335 in 2019. Conclusion The Irish COVID-19 outbreak has created obstacles for urological care. Nonetheless, urgent/emergent urological cases persist. Our unit has managed this to-date with flexible adaptation of service delivery. The global challenge posed by COVID-19 will demand ongoing resourcefulness to minimise impact on patients with time-sensitive urological conditions.

The Feasibility of High-Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) in Patients with Suspected Scaphoid Fractures.

INTRODUCTION: Diagnosing scaphoid fractures remains challenging. High-resolution peripheral quantitative computed tomography (HR-pQCT) might be a potential imaging technique, but no data are available on its feasibility to scan the scaphoid bone in vivo. METHODOLOGY: Patients (≥18 years) with a clinically suspected scaphoid fracture received an HR-pQCT scan of the scaphoid bone (three 10.2-mm stacks, 61-µm voxel size) with their wrist immobilized with a cast. Scan quality assessment and bone contouring were performed using methods originally developed for HR-pQCT scans of radius and tibia. The contouring algorithm was applied on coarse hand-drawn pre-contours of the scaphoid bone, and the resulting contours (AUTO) were manually corrected (sAUTO) when visually deviating from bone margins. Standard morphologic analyses were performed on the AUTO- and sAUTO-contoured bones. RESULTS: Ninety-one patients were scanned. Two out of the first five scans were repeated due to poor scan quality (40%) based on standard quality assessment during scanning, which decreased to three out of the next 86 scans (3.5%) when using an additional thumb cast. Nevertheless, after excluding one scan with an incompletely scanned scaphoid bone, post hoc grading revealed a poor quality in 14.9% of the stacks and 32.9% of the scans in the remaining 85 patients. After excluding two scans with contouring problems due to scan quality, bone indices obtained by AUTO- and sAUTO-contouring were compared in 83 scans. All AUTO-contours were manually corrected, resulting in significant but small differences in densitometric and trabecular indices (<1.0%). CONCLUSIONS: In vivo HR-pQCT scanning of the scaphoid bone is feasible in patients with a clinically suspected scaphoid fracture when using a cast with thumb part. The proportion of poor-quality stacks is similar to radius scans, and AUTO-contouring appears appropriate in good- and poor-quality scans . Thus, HR-pQCT may be promising for diagnosis of and microarchitectural evaluations in suspected scaphoid fractures.

Community-based monitoring detects catastrophic earthquake and tsunami impacts on seagrass beds in the Solomon Islands.

Tetepare Island in the Solomon Islands is the largest uninhabited island in the South Pacific and supports seagrass beds inside fringing reefs along its coastline. We monitored the diversity and abundance of seagrass species on Tetepare and nearby sparsely-populated Rendova Island over a 12 year period, 4 years before and up to 8 years after a major earthquake and tsunami event in January 2010. Both seagrass cover and diversity declined after the tsunami and had not reached pre-Tsunami levels after 8 years. Seagrass cover declined the fastest at sites on Rendova, closest to the epicentre, declining from 50% to <10% cover within 12 months of the earthquake. At sites within the Tetepare MPA, seagrass cover took longer to decline and dropped from an average of 50% to <10% within 2 years and became dominated by Halophila ovalis. Species richness declined from 9 to 4 species with some species such as Syringodium isoetifolium disappearing from monitoring sites. Community-based monitoring was an effective method of documenting long term changes in seagrass cover and long-term monitoring is required to determine if seagrass beds are permanently altered or return to pre-tsunami conditions.

Impact of obesity on operative treatment and inpatient outcomes of paediatric limb fractures.

AIMS: The aim of this study was to utilize a national paediatric inpatient database to determine whether obesity influences the operative management and inpatient outcomes of paediatric limb fractures. PATIENTS AND METHODS: The Kids' Inpatient Database (KID) was used to evaluate children between birth and 17 years of age, from 1997 and 2012, who had undergone open and closed treatment of humeral, radial and ulna, femoral, tibial, and ankle fractures. Demographics, hospital charges, lengths of stay (LOS), and complications were analyzed. RESULTS: Obesity was significantly associated with increased rates of open reduction and internal fixation (ORIF) for: distal humeral (odds ratio (OR) = 2.139, 95% confidence interval (CI) 1.92 to 3.44; p < 0.001); distal radius and ulna fractures (OR = 1.436, 95% CI 1.14 to 2.16; p < 0.05); distal femoral (OR = 2.051, 95% CI 1.69 to 3.60; p < 0.05); tibial and fibula shaft (OR = 2.101, 95% CI 2.10 to 3.50; p < 0.001); and ankle (OR = 1.733, 95% CI 1.70 to 2.39; p < 0.001). Older age was significantly associated with ORIF for all fractures (p < 0.05). LOS, hospital charges, and complications were significantly increased in obese patients following ORIF for upper and lower limb fractures (p < 0.05). CONCLUSION: Obese paediatric patients are more likely to undergo ORIF in both upper and lower limb fractures and have more inpatient complications. These findings may assist in informing obese paediatric fracture patients and their families regarding the increased risk for open operative fixation and associated outcomes. Cite this article: Bone Joint J 2019;101-B:491-496.

Inpatient surgical treatment of paediatric proximal humerus fractures between 2000 and 2012.

PURPOSE: To estimate the rate of surgical treatment of paediatric proximal humerus fractures over time utilizing a large, publicly available national database. METHODS: The Healthcare Cost and Utilization Project Kids' Inpatient Database was evaluated between the years 2000 and 2012. Proximal humerus fractures were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9 CM) diagnosis codes. ICD-9 CM procedure codes were used to identify patients who received surgical treatment. Univariable and multivariable logistic regression were used to determine variables associated with greater proportions of surgical treatment. All statistical analyses were performed utilizing SAS statistical software v.9.4. Statistical significance was set at p < 0.05. RESULTS: A total of 7520 proximal humerus fracture admissions were identified; 3247 (43.2%) were treated surgically. The percentage of patients receiving surgery increased from 39.3% in 2000 to 46.4% in 2012 (p < 0.001). After adjustment for potential confounders, increased age, increased ICD-9 derived injury severity scores (ICISS) and more recent year were associated with an increased proportion of patients receiving surgical treatment (p < 0.001). Medicaid payer status (p < 0.001) and admission to a children's hospital (p = 0.045) were associated with a lower proportion of surgical treatment. CONCLUSION: The rate of operative treatment of paediatric proximal humerus fractures increased over time between 2000 and 2012. Increased surgical rates were independently associated with older age, increased ICISS, treatment at a non-children's hospital and non-Medicaid insurance status. Further study is needed to provide evidence to support improved outcomes after operative treatment of paediatric proximal humerus fractures.

Maternal cardiac output response to colloid preload and vasopressor therapy during spinal anaesthesia for caesarean section in patients with severe pre-eclampsia: a randomised, controlled trial.

We examined the haemodynamic effects of colloid preload, and phenylephrine and ephedrine administered for spinal hypotension, during caesarean section in 42 women with severe early onset pre-eclampsia. Twenty patients with pre-delivery spinal hypotension were randomly allocated to receive an initial dose of either 50 µg phenylephrine or 7.5 mg ephedrine; the primary outcome was percentage change in cardiac index. After a 300-ml colloid preload, mean (SD) cardiac index increased from 4.9 (1.1) to 5.6 (1.2) l.min-1 .m-2 (p < 0.01), resulting from an increase in both heart rate, from 81.3 (17.2) to 86.3 (16.5) beats.min-1 (p = 0.2), and stroke volume, from 111.8 (19.0) to 119.8 (17.9) ml (p = 0.049). Fourteen (33%) and 23 (54.8%) patients exhibited a stroke volume response > 10% and > 5%, respectively; a significant negative correlation was found between heart rate and stroke volume changes. Spinal hypotension in 20 patients was associated with an increase from baseline in cardiac index of 0.6 l.min-1 .m-2 (mean difference 11.5%; p < 0.0001). After a median [range] dose of 50 [50-150] µg phenylephrine or 15 [7.5-37.5] mg ephedrine, the percentage change in cardiac index during the measurement period of 150 s was greater, and negative, in patients receiving phenylephrine vs. ephedrine, at -12.0 (7.3)% vs. 2.6 (6.0)%, respectively (p = 0.0001). The percentage change in heart rate after vasopressor was higher in patients receiving phenylephrine, at -9.1 (3.4)% vs. 5.3 (12.6)% (p = 0.0027), as was the change in systemic vascular resistance, at 22.3 (7.5) vs. -1.9 (10.5)% (p < 0.0001). Phenylephrine effectively reverses spinal anaesthesia-induced haemodynamic changes in severe pre-eclampsia, if left ventricular systolic function is preserved.

The African Hospitalist Fellowship.

The African Paediatric Fellowship Programme is rolling out a training course for newly qualified paediatricians to equip them with the leadership skills to function in complex general paediatric settings. The care of children in Africa carries its own unique demands, from the layering effects of multiple conditions through to establishing and sustaining services under severe resource constraints. This novel training concept aims to strengthen confidence and knowledge in areas that are not priorities during standard general paediatric training. The skills gained are considered of great relevance in assisting general paediatricians to achieve their full potential in their careers.

Computed tomographic findings in 12 cases of canine multi-centric lymphoma with splenic and hepatic involvement.

OBJECTIVES: To describe the CT findings in a population of dogs with multi-centric lymphoma that involved the spleen and liver. MATERIALS AND METHODS: Clinical records between January 2008 and June 2015 were reviewed. Thoracic and abdominal CT examinations of patients diagnosed with multi-centric lymphoma were evaluated by a board-certified radiologist. A diagnosis of multi-centric lymphoma with splenic and hepatic involvement was based upon cytological identification and immunophenotyping of neoplastic lymphocytes in cellular samples harvested from a peripheral lymph node, the spleen and the liver. RESULTS: Twelve dogs were included in this study, of which 11 had B-cell lymphoma; immunophenotyping was inconclusive in one dog. The spleen appeared normal in seven dogs and nodules were identified in five dogs. Splenic nodules were hypoattenuating in four of five dogs and isoattenuating in one of five. After contrast administration, three of five appeared hypoattenuating and two of five isoattenuating. The liver appeared normal in 10 dogs and hepatic nodules were identified in two dogs. All hepatic nodules were isoattenuating before contrast and hypoattenuating following contrast administration. CLINICAL SIGNIFICANCE: The CT appearance of the spleen and liver was normal in the majority of dogs with multi-centric lymphoma. Fine needle aspiration of the spleen and liver is recommended when using CT to stage dogs with multi-centric lymphoma.

Increasing rates of surgical treatment for paediatric diaphyseal forearm fractures: a National Database Study from 2000 to 2012.

FOREARM: Purpose fractures are one of the most commonly sustained injuries in children and are often treated non-operatively. The purpose of this study was to estimate the rate of inpatient surgical treatment of paediatric forearm fractures over time using a large, publicly available, national database. METHODS: The Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID) was evaluated between 2000 and 2012. Forearm fractures and surgeries were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9 CM) diagnosis and procedure codes. Univariable and multivariable logistic regression were used to determine variables associated with greater proportion of surgical treatment. All statistical analyses were performed using SAS statistical software v.9.4 (SAS Institute Inc., Cary, NC, USA). Statistical significance was set at p < 0.05. RESULTS: The database identified 30 936 forearm fracture admissions. Overall, 19 837 of these patients were treated surgically (64.12%). The percentage of patients treated with surgery increased from 59.3% in 2000 to 70.0% in 2012 (p < 0.001). Multivariable regression analysis found increased age (p < 0.001), more recent year (p < 0.001), male gender (p = 0.003) and admission to a children's hospital (p < 0.001) were associated with an increased proportion of patients receiving surgical treatment. Medicaid payer status was associated with a lower proportion of surgical treatment (p < 0.001). CONCLUSIONS: The rate of operative treatment for paediatric forearm fractures admitted to the hospital increased over time. Increased surgical rates were associated with older age, male gender, treatment at a children's hospital and non-Medicaid insurance status.

The neuronal metabolite NAA regulates histone H3 methylation in oligodendrocytes and myelin lipid composition.

The neuronal mitochondrial metabolite N-acetylaspartate (NAA) is decreased in the multiple sclerosis (MS) brain. NAA is synthesized in neurons by the enzyme N-acetyltransferase-8-like (NAT8L) and broken down in oligodendrocytes by aspartoacylase (ASPA) into acetate and aspartate. We have hypothesized that NAA links the metabolism of axons with oligodendrocytes to support myelination. To test this hypothesis, we performed lipidomic analyses using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high-performance thin-layer chromatography (HPTLC) to identify changes in myelin lipid composition in postmortem MS brains and in NAT8L knockout (NAT8L-/-) mice which do not synthesize NAA. We found reduced levels of sphingomyelin in MS normal appearing white matter that mirrored decreased levels of NAA. We also discovered decreases in the amounts of sphingomyelin and sulfatide lipids in the brains of NAT8L-/- mice compared to controls. Metabolomic analysis of primary cultures of oligodendrocytes treated with NAA revealed increased levels of α-ketoglutarate, which has been reported to regulate histone demethylase activity. Consistent with this, NAA treatment resulted in alterations in the levels of histone H3 methylation, including H3K4me3, H3K9me2, and H3K9me3. The H3K4me3 histone mark regulates cellular energetics, metabolism, and growth, while H3K9me3 has been linked to alterations in transcriptional repression in developing oligodendrocytes. We also noted the NAA treatment was associated with increases in the expression of genes involved in sulfatide and sphingomyelin synthesis in cultured oligodendrocytes. This is the first report demonstrating that neuronal-derived NAA can signal to the oligodendrocyte nucleus. These data suggest that neuronal-derived NAA signals through epigenetic mechanisms in oligodendrocytes to support or maintain myelination.

Clinical-scale in vitro expansion preserves biological characteristics of cardiac atrial appendage stem cells.

OBJECTIVES: Cardiac atrial appendage stem cells (CASCs) have recently emerged as an attractive candidate for cardiac regeneration after myocardial infarction. As with other cardiac stem cells, CASCs have to be expanded ex vivo to obtain clinically relevant cell numbers. However, foetal calf serum (FCS), which is routinely used for cell culturing, is unsuitable for clinical purposes, and influence of long-term in vitro culture on CASC behaviour is unknown. MATERIALS AND METHODS: We examined effects on CASC biology of prolonged expansion, and evaluated a culture protocol suitable for human use. RESULTS: In FCS-supplemented medium, CASCs could be kept in culture for 55.75 ± 3.63 days, before reaching senescence. Despite a small reduction in numbers of proliferating CASCs (1.37 ± 0.52% per passage) and signs of progressive telomere shortening (0.04 ± 0.02 kb per passage), their immunophenotype and myocardial differentiation potential remained unaffected during the entire culture period. The cells were successfully expanded in human platelet plasma supernatant, while maintaining their biological properties. CONCLUSIONS: We successfully developed a protocol for long-term culture, to obtain clinically relevant CASC numbers, while retaining their cardiogenic potential. These insights in CASC biology and optimization of a humanized platelet-based culture method are an important step towards clinical application of CASCs for cardiac regenerative medicine.

Dynamics of culling for Jersey, Holstein, and Jersey × Holstein crossbred cows in large multibreed dairy herds.

The objective of this observational study was to describe and compare the dynamics of reason-specific culling risk for the genetic groups Jerseys (JE), Holsteins (HO), and Jersey × Holstein crossbreds (JH), considering parity, stage of lactation, and milk yield, among other variables, in large multibreed dairy herds in Texas. The secondary objective was to analyze the association between survival and management factors, such as breeding and replacement policies, type of facilities, and use of cooling systems. After edits, available data included 202,384 lactations in 16 herds, ranging from 407 to 8,773 cows calving per year during the study period from 2007 to 2011. The distribution of lactation records by genetic group was 58, 36, and 6% for HO, JE, and JH crosses, respectively. Overall culling rates across breeds were 30.1, 32.1, and 35.0% for JH, JE, and HO, respectively. The dynamics of reason-specific culling were dependent on genetic group, parity, stage of lactation, milk yield, and herd characteristics. Early lactation was a critical period for "died" and "injury-sick" culling. The risk increased with days after calving for "breeding" and, in the case of HO, "low production" culling. Open cows had a 3.5 to 4.6 times greater risk for overall culling compared with pregnant cows. The odds of culling with reason "died" within the first 60 d in milk (DIM) were not significantly associated with genetic group. However, both JE and JH crosses had lower odds of live culling within the first 60 DIM compared with HO cows (OR=0.72 and 0.82, respectively). Other cow variables significantly associated with the risk of dying within the first 60 DIM were cow relative 305-d mature equivalent (305ME) milk yield, parity, and season of calving. Significant herd-related variables for death included herd size and origin of replacements. In addition to genetic group, the risk of live culling within 60 DIM was associated with cow-relative 305ME milk yield, parity, and season of calving. Significant herd-related variables for live culling included herd-relative 305ME milk yield, herd size, type of facility, origin of replacement, and type of maternity. Overall, reason-specific culling followed similar patterns across DIM in the 3 genetic groups.

Emergence of opiate-induced neonatal abstinence syndrome.

Neonatal abstinence syndrome (NAS) is the clinical picture of infants withdrawing from in-utero substance exposure. The incidence of NAS rose in Dublin maternity hospitals in the 1970's and '80's in parallel with increasing in opiate abuse in that city. The purpose of this study was to determine if a similar pattern was emerging in Cork University Maternity Hospital. Data from the Erinville Hospital (2000-2007) and CUMH (2008-2011) were compared. Sixteen cases of NAS were identified, two at Erinville Hospital (22,987 deliveries; incidence = 0.09/1000 deliveries) and 14 at CUMH (37,414 deliveries; incidence = 0.38/1000 deliveries; p < 0.01). Five of the 16 mothers were using heroin, while ten were on methadone maintenance. All were multi-drug abusers. Newborns requiring pharmacotherapy for NAS (5/16) had prolonged hospitalisations compared to those requiring supportive care. NAS in Cork is increasing. Primary, secondary and tertiary preventative measures are warranted to prevent further escalation.