A review of the International Seabed Authority database DeepData from a biological perspective: challenges and opportunities in the UN Ocean Decade.

There is an urgent need for high-quality biodiversity data in the context of rapid environmental change. Nowhere is this need more urgent than in the deep ocean, with the possibility of seabed mining moving from exploration to exploitation, but where vast knowledge gaps persist. Regions of the seabed beyond national jurisdiction, managed by the International Seabed Authority (ISA), are undergoing intensive mining exploration, including the Clarion-Clipperton Zone (CCZ) in the Central Pacific. In 2019, the ISA launched its database 'DeepData', publishing environmental (including biological) data. Here, we explore how DeepData could support biological research and environmental policy development in the CCZ (and wider ocean regions) and whether data are findable, accessible, interoperable and reusable (FAIR). Given the direct connection of DeepData with the regulator of a rapidly developing potential industry, this review is particularly timely. We found evidence of extensive duplication of datasets; an absence of unique record identifiers and significant taxonomic data-quality issues, compromising FAIRness of the data. The publication of DeepData records on the OBIS ISA node in 2021 has led to large-scale improvements in data quality and accessibility. However, limitations in the usage of identifiers and issues with taxonomic information were also evident in datasets published on the node, stemming from mismapping of data from the ISA environmental data template to the data standard Darwin Core prior to data harvesting by OBIS. While notable data-quality issues remain, these changes signal a rapid evolution for the database and significant movement towards integrating with global systems, through the usage of data standards and publication on the global data aggregator OBIS. This is exactly what has been needed for biological datasets held by the ISA. We provide recommendations for the future development of the database to support this evolution towards FAIR. Database URL https://data.isa.org.jm/isa/map.

An unusual case of a penetrating neck injury (PNI) illustrating the use of a "no zone" approach for the management of this injury and a review of the literature.

We present an unusual case of a young male with a penetrating neck injury (PNI) due to a work-related injury. A metallic foreign body traversed from entry at surgical Zone 2 to Zone 1 in the neck and resulted in a transection of the left thyrocervical trunk at the origin with the left subclavian artery. Computed Tomographic Angiography (CTA) of the aortic arch and major branch vessels demonstrated haemorrhage anterior to the left subclavian artery and left thyrocervical trunk. We describe some of the diagnostic and operative challenges which may occur in these rare and life-threatening injuries. We have also reviewed some of the recent key literature on this topic and have collated the recommendations of the review. In recent years, there has been a movement away from selective "zone-based" mandatory surgical exploration for Zone 2 injuries, as well as invasive and time-consuming investigations (such as digital subtraction angiography, contrast oesophageal swallow and bronchoscopy) for Zone 1 and 3 injuries due to the high number of negative surgical procedures and investigations. We demonstrate there is now an evidence-based algorithm which demonstrates that a "no zone" approach to the management of these patients is safe and effective. This requires an initial physical examination looking for the presence or absence of "hard", "soft" or "no" physical signs in these patients, and then deciding on subsequent management which would include immediate surgery, CTA of the aortic arch and branches (and subsequent surgical or other management) or observation only. Our aim in describing this case it to highlight that there is now good evidence-based guidance for the safe and effective management of patients with this infrequent but potentially fatal injury.

Bilateral Craniofacial Cleft (Tessier Type 4): Case Report and Oculoplastic Reconstruction.

Bilateral Tessier type 4 craniofacial clefts are extremely rare and disfiguring malformations with vision-threatening ramifications. To date, there is no consensus in the literature with respect to the ideal surgical technique and management of these patients. Emergent eyelid reconstruction and additional procedures may be required to protect the cornea and avoid further ophthalmic and surgical complications. We present our experience and challenges of managing a case of bilateral Tessier type 4 clefting with an emphasis on oculoplastic considerations.

Risk of needing completion thyroidectomy for low-risk papillary thyroid cancers treated by lobectomy.

Background: Low-risk differentiated thyroid cancers may, according to the American Thyroid Association (ATA) 2015 guidelines, be managed initially with lobectomy. However, definitive risk categorization requires pathological assessment of the specimen, resulting in completion thyroidectomy being recommended when discordance between preoperative and postoperative staging occurs. This study sought to establish the expected rate of completion thyroidectomy in patients with papillary thyroid cancer (PTC) treated by lobectomy. Methods: Patients with PTC treated over 5 years (2013-2017 inclusive) and meeting the ATA criteria for lobectomy were identified from the prospectively developed database of a high-volume, university department of endocrine surgery. Concordance between the ATA initial and final recommendation, and the putative rate of completion thyroidectomy were calculated. Multivariable analysis was used to assess preoperative factors as predictors of the need for total thyroidectomy. Results: Of 275 patients with PTC who met ATA preoperative criteria for lobectomy there was concordance between this and the final recommendation in 158 (57·5 per cent) and discordance in 117 (43·5 per cent). Most common reasons for discordance were: angioinvasion (30·8 per cent), local invasion (23·9 per cent) or both (20·5 per cent). Four patients (1·5 per cent) had permanent hypoparathyroidism. On multivariable analysis, age, sex, tumour size and family history did not independently predict the final treatment required. Conclusion: Although many patients may be treated adequately with lobectomy, just under half would require completion thyroidectomy. Further work is needed on preoperative risk stratification but, before this, total thyroidectomy remains the treatment of choice for low-risk 1-4-cm PTC in the hands of high-volume thyroid surgeons who can demonstrate low complication rates.

Association of chorioamnionitis and its duration with adverse maternal outcomes by mode of delivery: a cohort study.

OBJECTIVE: To investigate the association of chorioamnionitis and its duration with adverse maternal outcomes by mode of delivery. DESIGN: A retrospective cohort study. SETTING: Data from the Consortium on Safe Labor Study in the USA (2002-2008). POPULATION: Singleton deliveries at ≥23 weeks of gestation (221 274 assessed deliveries, 62 331 by caesarean section). METHODS: The association of chorioamnionitis, and secondarily the duration of chorioamnionitis estimated from intrapartum antibiotic use, with adverse maternal outcomes was analysed using logistic regression with generalised estimating equations, adjusting for age, parity, race, pregestational diabetes, chronic hypertension, gestational age at delivery, study site and delivery year. Analyses were stratified by vaginal versus caesarean delivery. MAIN OUTCOME MEASURES: The composite adverse maternal outcome included: postpartum transfusion, endometritis, wound/perineal infection/separation, venous thromboembolism, hysterectomy, admission to intensive care unit and/or death. RESULTS: Chorioamnionitis was associated with higher odds of the composite adverse maternal outcome with caesarean delivery (adjusted odds ratio 2.31; 95% CI 1.97-2.71); and the association persisted regardless of whether a woman had a trial of labour, preterm delivery or maternal group B streptococcus colonisation. The most common adverse outcomes after caesarean section were postpartum transfusion (56.0%) and wound/perineal infection or endometritis (38.6%). Chorioamnionitis was not associated with adverse maternal outcomes after vaginal delivery. The duration of chorioamnionitis as the exposure did not alter the association between chorioamnionitis and adverse maternal outcomes. CONCLUSIONS: Chorioamnionitis, but not the estimated duration, was associated with increased odds of adverse maternal outcomes with caesarean delivery. This finding has implications for care programmes to prevent maternal morbidity after a caesarean section complicated by chorioamnionitis. TWEETABLE ABSTRACT: Chorioamnionitis, but not its duration, increases the risk of adverse maternal outcomes with caesarean delivery.

Genomic analysis to assess disease progression and recurrence in patients with oral squamous cell carcinoma: - a preliminary study.

We studied the progression from dysplasia to invasive carcinoma and subsequent second primaries or locoregional recurrences in 11 patients with recurrent squamous cell carcinoma (SCC). Between one and six samples were sequenced/patient. DNA samples were prepared, and libraries multiplexed to between 40 and 80 samples/lane of an Illumina HiSeq 3000 and sequenced with 2×100bp paired end sequencing. Copy number data were generated by CNAnorm (Bioconductor package). Samples of recurrent SCC showed unique patterns of descent when compared with earlier samples from the primary tumour, and three main patterns emerged. In four patients there was convincing evidence that the later lesion was descended directly from cells from the first, and in a further four there were no detectable genomic events between the two lesions. Three patients had some shared events between the early and later lesions, but although there were enough differences to deduce that the two lesions had a shared ancestor, they were not directly descended from each other. We present the patients' characteristics in detail, including the overall survival in each group. There was a distinct genomic pattern after a second episode of SCC in all the groups. A larger study that uses similar methods and a longer duration could provide reliable conclusions with respect to survival. With the use of new techniques, genomic data can be available to clinical teams during the planning of treatment.

Isolated cranio-orbitofacial neurofibroma mimicking vascular malformation.

Isolated neurofibromas in the absence of systemic neurofibromatosis are known as solitary or localized neurofibromas. When present in the orbit, these lesions may appear clinically and radiographically similar to other tumors, complicating diagnosis and management. Key radiographic signs may guide clinicians to the correct diagnosis when the presentation and patient demographic data obfuscate the disease entity. We present a case of a large multi-lobulated neurofibroma misdiagnosed as a lymphangioma. A brief review of these tumors emphasizing key radiographic features is also included.

Avoidance, biomass and survival response of soil dwelling (endogeic) earthworms to OECD artificial soil: potential implications for earthworm ecotoxicology.

Soil dwelling earthworms are now adopted more widely in ecotoxicology, so it is vital to establish if standardised test parameters remain applicable. The main aim of this study was to determine the influence of OECD artificial soil on selected soil-dwelling, endogeic earthworm species. In an initial experiment, biomass change in mature Allolobophora chlorotica was recorded in Standard OECD Artificial Soil (AS) and also in Kettering Loam (KL). In a second experiment, avoidance behaviour was recorded in a linear gradient with varying proportions of AS and KL (100% AS, 75% AS + 25% KL, 50% KS + 50% KL, 25% AS + 75% KL, 100% KL) with either A. chlorotica or Octolasion cyaneum. Results showed a significant decrease in A. chlorotica biomass in AS relative to KL, and in the linear gradient, both earthworm species preferentially occupied sections containing higher proportions of KL over AS. Soil texture and specifically % composition and particle size of sand are proposed as key factors that influenced observed results. This research suggests that more suitable substrates are required for ecotoxicology tests with soil dwelling earthworms.

Effects of silver nanoparticles on survival, biomass change and avoidance behaviour of the endogeic earthworm Allolobophora chlorotica.

Increasing commercial application of silver nanoparticles (Ag NP) and subsequent presence in wastewater and sewage sludge has raised concerns regarding their effects in the aquatic and terrestrial environment. Several studies have employed standardised acute and chronic earthworm-based tests to establish the toxicological effects of Ag NP within soil. These studies have relied heavily on the use of epigiec earthworm species which may have limited ecological relevance in mineral soil. This study assessed the influence of Ag NP (uncoated 80nm powder) and AgNO3 on survival, change in biomass and avoidance behaviour in a soil dwelling (endogiec) species, Allolobophora chlorotica. Earthworms were exposed for 14 days to soils spiked with Ag NP or AgNO3 at 0, 12.5, 25, 50 and 100mgkg-1 either separately for survival and biomass measurement, or combined within a linear gradient to assess avoidance. Avoidance behaviour was shown to provide the most sensitive endpoint with an observable effect at an Ag NP/AgNO3 concentration of 12.5mgkg-1 compared with 50mgkg-1 for biomass change and 100mgkg-1 for survival. Greater mortality was observed in AgNO3 (66.7%) compared with Ag NP-spiked soils (12.5%) at 100mgkg-1, attributed to increased presence of silver ions. Although comparison of results with studies employing Eisenia fetida and Eisenia andrei suggest that the A. chlorotica response to Ag NP is more sensitive, further research employing both epigeic and endogeic earthworms under similar experimental conditions is required to confirm this observation.

Orbital Mucormycosis Following Periorbital Cutaneous Infection.

Mucormycosis is an aggressive fungal infection characterized by rapidly progressive angioinvasion and tissue necrosis. When present in the orbit, mucormycosis can quickly lead to permanent visual loss and potentially fatal cerebral extension. Orbital involvement is almost universally preceded by infection of the paranasal sinuses. Secondary infection of the orbit via direct extension of neighboring cutaneous mucormycosis has not been previously described. The authors present a case of cutaneous mucormycosis with orbital extension in a poorly controlled diabetic patient.

Ecology and biogeography of megafauna and macrofauna at the first known deep-sea hydrothermal vents on the ultraslow-spreading Southwest Indian Ridge.

The Southwest Indian Ridge is the longest section of very slow to ultraslow-spreading seafloor in the global mid-ocean ridge system, but the biogeography and ecology of its hydrothermal vent fauna are previously unknown. We collected 21 macro- and megafaunal taxa during the first Remotely Operated Vehicle dives to the Longqi vent field at 37° 47'S 49° 39'E, depth 2800 m. Six species are not yet known from other vents, while six other species are known from the Central Indian Ridge, and morphological and molecular analyses show that two further polychaete species are shared with vents beyond the Indian Ocean. Multivariate analysis of vent fauna across three oceans places Longqi in an Indian Ocean province of vent biogeography. Faunal zonation with increasing distance from vents is dominated by the gastropods Chrysomallon squamiferum and Gigantopelta aegis, mussel Bathymodiolus marisindicus, and Neolepas sp. stalked barnacle. Other taxa occur at lower abundance, in some cases contrasting with abundances at other vent fields, and δ13C and δ15N isotope values of species analysed from Longqi are similar to those of shared or related species elsewhere. This study provides baseline ecological observations prior to mineral exploration activities licensed at Longqi by the United Nations.

Predicting failure of glyburide therapy in gestational diabetes.

OBJECTIVE: We sought to develop a prediction model to identify women with gestational diabetes (GDM) who require insulin to achieve glycemic control. STUDY DESIGN: Retrospective cohort of all singletons with GDM treated with glyburide from 2007 to 2013. Glyburide failure was defined as reaching glyburide 20 mg day(-1) and receiving insulin. Glyburide success was defined as any glyburide dose without insulin and >70% of visits with glycemic control. Multivariable logistic regression analysis was performed to create a prediction model. RESULT: Of the 360 women, 63 (17.5%) qualified as glyburide failure and 157 (43.6%) as glyburide success. The final prediction model for glyburide failure included prior GDM, GDM diagnosis ⩽26 weeks, 1-h glucose challenge test ⩾228 mg dl(-1), 3-h glucose tolerance test 1-h value ⩾221 mg dl(-1), ⩾7 postprandial blood sugars >120 mg dl(-1) in the week glyburide started and ⩾1 blood sugar >200 mg dl(-1). The model accurately classified 81% of subjects. CONCLUSION: Women with GDM who will require insulin can be identified at the initiation of pharmacological therapy.

Top ten research priorities for spinal cord injury: the methodology and results of a British priority setting partnership.

STUDY DESIGN: This is a mixed-method consensus development project. OBJECTIVES: The objective of this study was to identify a top ten list of priorities for future research into spinal cord injury (SCI). SETTING: The British Spinal Cord Injury Priority Setting Partnership was established in 2013 and completed in 2014. Stakeholders included consumer organisations, healthcare professional societies and caregivers. METHODS: This partnership involved the following four key stages: (i) gathering of research questions, (ii) checking of existing research evidence, (iii) interim prioritisation and (iv) a final consensus meeting to reach agreement on the top ten research priorities. Adult individuals with spinal cord dysfunction because of trauma or non-traumatic causes, including transverse myelitis, and individuals with a cauda equina syndrome (henceforth grouped and referred to as SCI) were invited to participate in this priority setting partnership. RESULTS: We collected 784 questions from 403 survey respondents (290 individuals with SCI), which, after merging duplicate questions and checking systematic reviews for evidence, were reduced to 109 unique unanswered research questions. A total of 293 people (211 individuals with SCI) participated in the interim prioritisation process, leading to the identification of 25 priorities. At a final consensus meeting, a representative group of individuals with SCI, caregivers and health professionals agreed on their top ten research priorities. CONCLUSION: Following a comprehensive, rigorous and inclusive process, with participation from individuals with SCI, caregivers and health professionals, the SCI research agenda has been defined by people to whom it matters most and should inform the scope and future activities of funders and researchers for the years to come. SPONSORSHIP: The NIHR Oxford Biomedical Research Centre provided core funding for this project.

Mineralization of Alvinella polychaete tubes at hydrothermal vents.

Alvinellid polychaete worms form multilayered organic tubes in the hottest and most rapidly growing areas of deep-sea hydrothermal vent chimneys. Over short periods of time, these tubes can become entirely mineralized within this environment. Documenting the nature of this process in terms of the stages of mineralization, as well as the mineral textures and end products that result, is essential for our understanding of the fossilization of polychaetes at hydrothermal vents. Here, we report in detail the full mineralization of Alvinella spp. tubes collected from the East Pacific Rise, determined through the use of a wide range of imaging and analytical techniques. We propose a new model for tube mineralization, whereby mineralization begins as templating of tube layer and sublayer surfaces and results in fully mineralized tubes comprised of multiple concentric, colloform, pyrite bands. Silica appeared to preserve organic tube layers in some samples. Fine-scale features such as protein fibres, extracellular polymeric substances and two types of filamentous microbial colonies were also found to be well preserved within a subset of the tubes. The fully mineralized Alvinella spp. tubes do not closely resemble known ancient hydrothermal vent tube fossils, corroborating molecular evidence suggesting that the alvinellids are a relatively recent polychaete lineage. We also compare pyrite and silica preservation of organic tissues within hydrothermal vents to soft tissue preservation in sediments and hot springs.

Long noncoding RNA profiles of adrenocortical cancer can be used to predict recurrence.

Adrenocortical carcinoma (ACC) is an aggressive malignancy with high rates of recurrence following surgical resection. Long noncoding RNAs (lncRNAs) play an important role in cancer development. Pathogenesis of adrenal tumours have been characterised by mRNA, microRNA and methylation expression signatures, but it is unknown if this extends to lncRNAs. This study describes lncRNA expression signatures in ACC, adrenal cortical adenoma (ACA) and normal adrenal cortex (NAC) and presents lncRNAs associated with ACC recurrence to identify novel prognostic and therapeutic targets. RNA was extracted from freshly frozen tissue with confirmation of diagnosis by histopathology. Focused lncRNA and mRNA transcriptome analysis was performed using the ArrayStar Human LncRNA V3.0 microarray. Differentially expressed lncRNAs were validated using quantitative reverse transcriptase-PCR and correlated with clinical outcomes. Microarray of 21 samples (ten ACCs, five ACAs and six NACs) showed distinct patterns of lncRNA expression between each group. A total of 956 lncRNAs were differentially expressed between ACC and NAC, including known carcinogenesis-related lncRNAs such as H19, GAS5, MALAT1 and PRINS (P≤0.05); 85 lncRNAs were differentially expressed between ACC and ACA (P≤0.05). Hierarchical clustering and heat mapping showed ACC samples correctly grouped compared with NAC and ACA. Sixty-six differentially expressed lncRNAs were found to be associated with ACC recurrence (P≤0.05), one of which, PRINS, was validated in a group of 20 ACCs and also found to be associated with metastatic disease on presentation. The pathogenesis of adrenal tumours extends to lncRNA dysregulation and low expression of the lncRNA PRINS is associated with ACC recurrence.

Outcomes of routine ilioinguinal lymph node dissection for palpable inguinal melanoma nodal metastasis.

BACKGROUND: Patients who present with palpable inguinal melanoma nodal metastasis have two surgical options: inguinal or ilioinguinal lymph node dissection. Indications for either operation remain controversial. This study examined survival and recurrence outcomes following ilioinguinal dissection for patients with palpable inguinal nodal metastasis, and assessed the incidence and preoperative predictors of pelvic nodal metastasis. METHODS: This was a retrospective clinicopathological analysis of consecutive surgical patients with stage III malignant melanoma. All patients underwent a standardized ilioinguinal dissection at a specialist tertiary oncology hospital over a 12-year period (1998-2010). RESULTS: Some 38.9 per cent of 113 patients had metastatic pelvic nodes. Over a median follow-up of 31 months, the 5-year overall survival rate was 28 per cent for patients with metastatic inguinal and pelvic nodes, and 51 per cent for those with inguinal nodal metastasis only (P = 0.002). The nodal basin control rate was 88.5 per cent. Despite no evidence of pelvic node involvement on preoperative computed tomography (CT), six patients (5.3 per cent) with a single metastatic inguinal lymph node had metastatic pelvic lymph nodes. Logistic regression analysis showed that the number of metastatic inguinal nodes (odds ratio 1.56; P = 0.021) and suspicious CT findings (odds ratio 9.89; P = 0.001) were both significantly associated with metastatic pelvic nodes. The specificity of CT was good (89.2 per cent) in detecting metastatic pelvic nodes, but the sensitivity was limited (57.9 per cent). CONCLUSION: Metastatic pelvic nodes are common when palpable metastatic inguinal nodes are present. Long-term survival can be achieved following their resection by ilioinguinal dissection. As metastatic pelvic nodes cannot be diagnosed reliably by preoperative CT, patients presenting with palpable inguinal nodal metastasis should be considered for ilioinguinal dissection.

A double-blind block randomized clinical trial on the effect of zinc as a treatment for diarrhea in neonatal Holstein calves under natural challenge conditions.

Diarrhea is the leading cause of death in neonatal calves and contributes to major economic losses. The objective of this double-blind randomized clinical trial was to evaluate the effect of oral inorganic or organic zinc supplementation as a treatment for neonatal diarrhea in calves. Seventy nine 1 to 8 day old male Holstein calves on a California calf ranch were block randomized to one of 3 treatments within 24h from their first onset of diarrhea. Calves received a daily dose of either a placebo composed of 80 mg of zinc-free powder, 381.54 mg of zinc methionine (Met) (equivalent to 80 mg of zinc), or 99.69 mg of zinc oxide (ZO) (equivalent to 80 mg of zinc) in 2L of a zinc-free oral rehydration solution (ORS). Calves were treated once daily until normal fecal consistency or for a maximum of 14 days. Upon enrollment and exit, calves were weighed, and blood, feces, and liver biopsies were collected for trace mineral analysis. Fecal samples at enrollment and exit were tested for E. coli K99, Cryptosporidium spp., rotavirus and coronavirus. Pre-treatment liver zinc concentrations for the 71 calves in the placebo, zinc Met, and ZO treatment groups were 710.6 (SEM=147.7), 852.3 (SEM=129.6), and 750.7 (SEM=202.9)mg/kg dry weight (DW), respectively. Exit liver zinc concentrations for the calves in the placebo, zinc Met, and ZO treatment groups were 728.9 (SEM=182.9), 1141.0 (SEM=423.8), and 636.8 (SEM=81.5)mg/kg dry weight, respectively. Although statistically non-significant, there were clinically important findings identified for each of zinc Met and ZO treatments. Calves treated with zinc Met gained on average 40 g/day during a diarrhea episode compared to a weight loss of 67 g/day on average in the placebo-treated calves (Power 19.9%). Calves treated with ZO had 1.4 times higher hazard of clinical cure compared to calves in the placebo group (Power 5.3%). Calves that were fecal positive to cryptosporidium spp. at enrollment and treated with zinc Met had higher odds of testing negative at exit compared to placebo calves (Odds Ratio (OR)=16.0). In contrast, calves treated with ZO tended to recover (fecal score=1) one day earlier compared to calves treated with a placebo (8.5 d vs. 9.7 d). The current trial identified clinically important findings that warrant further research to investigate zinc's therapeutic effect for calf diarrhea.

Is there a role for free breathing non-contrast steady-state free precession renal MRA imaging for assessing live donors? A preliminary study.

OBJECTIVE: Accurate pre-operative evaluation of renal vascular anatomy is essential for successful renal harvest in live donor transplantation. Non-contrast renal MR angiographic (MRA) techniques are potentially well suited to the screening of donors; however, their restricted imaging field of view (FOV) has previously been an important limitation. We sought to assess whether the addition of a large FOV balanced fast field echo (BFFE) steady-state free precession (SSFP) sequence to non-contrast SSFP MRA could overcome this problem. Comparison with contrast-enhanced MRA (CE MRA) and findings at surgery were performed. METHODS: 22 potential renal donors each underwent SSFP and CE MRA. 11 out of 22 potential donors subsequently underwent a donor nephrectomy. RESULTS: All images were diagnostic. Both SSFP MRA and CE MRA identified an equal number of arteries. Surgery confirmed two accessory renal arteries, both demonstrated with both imaging techniques. A third accessory vessel was identified with both techniques on a kidney contralateral to the donated organ. 6 out of 11 procured kidneys demonstrated early branch arteries at surgery, 5 out of 6 of which had been depicted on both SSFP and CE MRA. The median grading of image quality for main renal arteries was slightly better for CE MRA (p=0.048), but for accessory vessels it was better for SSFP MRA. CONCLUSION: This pilot study indicates that by combining free-breathing SSFP MRA with large-FOV bFFE images, an accurate depiction of renal vascular anatomy without the need for intravenous contrast administration can be obtained, as compared with surgical findings and CE MRA.

Muscle histology vs MRI in Duchenne muscular dystrophy.

OBJECTIVE: There are currently no effective treatments to halt the muscle breakdown in Duchenne muscular dystrophy (DMD), although genetic-based clinical trials are being piloted. Most of these trials have as an endpoint the restoration of dystrophin in muscle fibers, hence requiring sufficiently well-preserved muscle of recruited patients. The choice of the muscles to be studied and the role of noninvasive methods to assess muscle preservation therefore require further evaluation. METHODS: We studied the degree of muscle involvement in the lower leg muscles of 34 patients with DMD >8 years, using muscle MRI. In a subgroup of 15 patients we correlated the muscle MRI findings with the histology of open extensor digitorum brevis (EDB) muscle biopsies. Muscle MRI involvement was assigned using a scale 0-4 (normal-severe). RESULTS: In all patients we documented a gradient of involvement of the lower leg muscles: the posterior compartment (gastrocnemius > soleus) was most severely affected; the anterior compartment (tibialis anterior/posterior, popliteus, extensor digitorum longus) least affected. Muscle MRI showed EDB involvement that correlated with the patient's age (p = 0.055). We show a correlation between the MRI and EDB histopathologic changes, with MRI 3-4 grades associated with a more severe fibro-adipose tissue replacement. The EDB was sufficiently preserved for bulk and signal intensity in 18/22 wheelchair users aged 10-16.6 years. CONCLUSION: This study provides a detailed correlation between muscle histology and MRI changes in DMD and demonstrates the value of this imaging technique as a reliable tool for the selection of muscles in patients recruited into clinical trials.