Publications by authors named "Mark Moore"

111 Publications

Bedside Ultrasound Conducted in Kids with distal upper Limb fractures in the Emergency Department (BUCKLED): a protocol for an open-label non-inferiority diagnostic randomised controlled trial.

Trials 2021 Apr 14;22(1):282. Epub 2021 Apr 14.

School of Medicine and Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia.

Background: Children frequently present to the emergency department (ED) with forearm injuries and often have x-rays to determine if there is a fracture. Bedside ultrasound, also known as point-of-care ultrasound (POCUS), is an alternative diagnostic test used to rapidly diagnose a fracture at the time of examination, without exposing children to ionising radiation. Prospective studies have demonstrated high agreement between POCUS and x-ray findings. However, whether the initial imaging modality affects the patient's medium-term physical function is unknown.

Methods: This is a multicentre, open-label, non-inferiority randomised controlled trial conducted in Australian EDs. Recruitment will continue until 112 children with distal forearm injuries (including 48 buckle fractures) per trial arm have achieved the primary outcome measure. Patients aged 5-15 years presenting with an isolated, acute, clinically non-angulated, distal forearm injury with suspected fracture will have their initial diagnostic approach randomised to either POCUS, performed by a credentialled practitioner, or x-ray imaging. If a cortical breach fracture is identified on POCUS, the patient will receive x-rays and have usual care. If a buckle fracture is identified, the patient will have their forearm placed in a splint and be discharged home. Patients will be followed up at 1, 4 and 8 weeks. The primary outcome is upper limb physical function at 4 weeks, as determined by the Pediatric Upper Extremity Short Patient-Reported Outcomes Measurement Information System (PROMIS) tool. Secondary outcomes include healthcare costs, satisfaction, pain, complications, rates of imaging, ED length of stay and diagnostic accuracy.

Discussion: If POCUS is non-inferior to x-ray in terms of patient's medium-term physical function, it may have an effect on overall health care resource use, including the number of x-ray performed and earlier ED discharge. Although prospective studies have confirmed the accuracy of POCUS, this will be the first RCT to assess non-inferiority of functional outcomes of POCUS to diagnose non-angulated paediatric distal forearm injuries, compared to x-ray. POCUS may be of particular importance in settings where access to x-ray imaging can be limited either during or after-hours, as it can aid the triaging and management of patients.

Trial Registration: Prospectively registered with the ANZCTR on 29 May 2020 ( ACTRN12620000637943 ).
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http://dx.doi.org/10.1186/s13063-021-05239-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048294PMC
April 2021

A large database study of hospitalization charges and follow-up re-admissions in US lumbar fusion surgeries using a cellular bone allograft (CBA) versus recombinant human bone morphogenetic protein-2 (rhBMP-2).

J Orthop Surg Res 2020 Nov 19;15(1):544. Epub 2020 Nov 19.

Global Clinical Affairs, LifeNet Health®, Virginia Beach, VA, USA.

Background: The objective of this study was to retrospectively compare initial procedure and 12-month follow-up hospitalization charges and resource utilization (lengths of stay; LOS) for lumbar fusion surgeries using either recombinant human bone morphogenetic protein-2 (rhBMP-2) or a cellular bone allograft comprised of viable lineage-committed bone cells (V-CBA) via a large US healthcare system database. Potentially relevant re-admissions during the follow-up period were also assessed.

Methods: A total of 16,172 patients underwent lumbar fusion surgery using V-CBA or rhBMP-2, of whom 3503 (21.66%) patients had follow-up re-admission data. Initial patient, procedure, and hospital characteristics were assessed to determine confounding factors. Multivariate regression modeling compared differences in hospitalization charges (in 2018 US dollars) and LOS (in days) between the groups, as well as incidences of potentially relevant re-admissions during the 12-month follow-up period.

Results: The adjusted mean initial procedure and 12-month follow-up hospital charges were significantly lower in the V-CBA group versus the rhBMP-2 group ($109,061 and $108,315 versus $160,191 and $130,406, respectively; P < 0.0001 for both comparisons). This disparity remained in an ad hoc comparison of charges for initial single-level treatments only (V-CBA = $103,064, rhBMP-2 = $149,620; P < 0.0001). The adjusted mean initial LOS were significantly lower in the V-CBA group (3.77 days) versus the rhBMP-2 group (3.88 days; P < 0.0001), but significantly higher for the cumulative follow-up hospitalizations in the 12-month follow-up period (7.87 versus 7.46 days, respectively; P < 0.0001). Differences in rates of follow-up re-admissions aligned with comorbidities at the initial procedure. Subsequent lumbar fusion rates were comparable, but significantly lower for V-CBA patients who had undergone single-level treatments only, in spite of V-CBA patients having significantly higher rates of initial comorbidities that could negatively impact clinical outcomes.

Conclusions: The results of this study indicate that use of V-CBA for lumbar fusion surgeries performed in the US may result in substantially lower overall hospitalization charges versus rhBMP-2, with both exhibiting similar rates of 12-month re-admissions and subsequent lumbar fusion procedures.
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http://dx.doi.org/10.1186/s13018-020-02078-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678152PMC
November 2020

Implications of increasing Atlantic influence for Arctic microbial community structure.

Sci Rep 2020 11 6;10(1):19262. Epub 2020 Nov 6.

Cellular and Molecular Department, The Marine Biological Association of the UK, Plymouth, PL1 2PB, UK.

Increasing influence of Atlantic water in the Arctic Ocean has the potential to significantly impact regional water temperature and salinity. Here we use a rDNA barcoding approach to reveal how microbial communities are partitioned into distinct assemblages across a gradient of Atlantic-Polar Water influence in the Norwegian Sea. Data suggest that temperate adapted bacteria may replace cold water taxa under a future scenario of increasing Atlantic influence, but the eukaryote response is more complex. Some abundant eukaryotic cold water taxa could persist, while less abundant eukaryotic taxa may be replaced by warmer adapted temperate species. Furthermore, within lineages, different taxa display evidence of increased relative abundance in reaction to favourable conditions and we observed that rare microbial taxa are sample site rather than region specific. Our findings have significant implications for the vulnerability of polar associated community assemblages, which may change, impacting the ecosystem services they provide, under predicted increases of Atlantic mixing and warming within the Arctic region.
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http://dx.doi.org/10.1038/s41598-020-76293-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648788PMC
November 2020

Severe Cloverleaf Skull Deformity in c.1061C>G (p.Ser354Cys) Mutated Fibroblast Growth Factor Receptor 2 Gene in Crouzon Syndrome.

J Craniofac Surg 2021 Jan-Feb 01;32(1):261-264

Australian Craniofacial Unit.

Abstract: Cloverleaf skull deformity (CSD), or Kleeblattschädel, is a condition with severe and unpatterned multisuture craniosynostosis, resulting in a trilobar-shaped skull. This deformity mainly comprises a cranio-orbito-facial malformation that leads to a spectrum of multidisciplinary issues. Several syndromes are associated with CSD, such as Crouzon syndrome (CS). Here, we report the case of an infant with CS and the pathogenic c.1061C>G (p.Ser354Cys) variant of the fibroblast growth factor receptor 2 (FGFR2) gene. The child presented with the severe form of CSD despite having a normal, mid-trimester, sonographic scan.
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http://dx.doi.org/10.1097/SCS.0000000000006999DOI Listing
September 2020

Neo-Sagittal Suture Formation After Cranial Vault Remodeling in Sagittal Craniosynostosis.

J Craniofac Surg 2021 Jan-Feb 01;32(1):282-284

Australian Craniofacial Unit, Women's and Children's Hospital, North Adelaide.

Abstract: Craniosynostosis is a condition where the cranial sutures are early fused. Sagittal suture synostosis is found to be the most prevalent. Many techniques ranging from simple suture excision to wide suturectomy have been developed for treating this condition. While repeated fusion of previously excised involved sutures is common, neosuture formation has been identified in many recent reports after craniosynostosis surgery. In this case report, the authors present a finding of the neosuture formation in a patient presented with sagittal craniosynostosis after wide suturectomy with total cranial vault remodeling so that the pathologically fused suture can be reversed.
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http://dx.doi.org/10.1097/SCS.0000000000007072DOI Listing
September 2020

Bilateral Mastoid Process Hypertrophy Associated With Severe Trismus.

J Craniofac Surg 2020 Sep 15. Epub 2020 Sep 15.

Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital, Wellington, New Zealand.

The mastoid process, a pneumatized prominence of the temporal bone with air-filled air cells, grows with age. We present here a series of 4 patients with bilateral mastoid hypertrophy associated with severe trismus from different etiologies, and discuss the possible explanation of this observation.
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http://dx.doi.org/10.1097/SCS.0000000000007057DOI Listing
September 2020

Late presenting bilateral squamosal synostosis.

Arch Craniofac Surg 2020 Apr 20;21(2):106-108. Epub 2020 Apr 20.

Australian Craniofacial Unit, Adelaide, Australia.

Premature fusion of one or other of the minor sutures can subtly influence the shape of the human skull. Although infrequently reported or not clinically recognized, it can such contribute to a variety of craniofacial dysmorphisms. We herein report a case of late presenting, isolated bilateral synostosis of the squamosal suture dysmorphologies whose presentation mimics aspects of sagittal synostosis.
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http://dx.doi.org/10.7181/acfs.2019.00073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206455PMC
April 2020

Cleidocranial Dysplasia: Management of the Multiple Craniofacial and Skeletal Anomalies.

J Craniofac Surg 2020 Jun;31(4):908-911

Australian Craniofacial Unit.

Cleidocranial dysplasia (CCD) is a rare autosomal dominant disorder caused by mutations in the Runx2 gene. The CCD is characterized by frontal bossing, a patent anterior fontanelle, presence of Wormian bones, midface hypoplasia, multiple dental abnormalities, clavicular hypoplasia or aplasia, skeletal abnormalities, and short stature. The aims of this study are to report the phenotypic manifestations of all patients who presented with CCD and to review the multidisciplinary management of these patients. The longitudinal data of patients with a diagnosis of CCD treated at The Australian Craniofacial Unit from 1980 to 2019 were reviewed. Fourteen patients were identified for inclusion in this study. The age at referral to the unit ranged from 1 week old to 49 years old (mean 11.2 years old). All patients had clinical features of frontal bossing, a patent anterior fontanelle, multiple Wormian bones, midface hypoplasia, abnormal dentition, clavicular hypoplasia/aplasia, and normal intellect. Eleven patients had obstructive sleep apnea. Eight patients had positive family history. Speech issues were found in 6 patients and abnormal hearing was found in 4 patients. Seven patients who underwent skeletal survey were found to have skeletal abnormalities. All patients were evaluated and managed by the multidisciplinary team, which consisted of craniofacial surgeons, pediatric dentists, orthodontists, ENT surgeons, pediatricians, clinical geneticists, radiologists, orthopedic surgeons, and social workers. All patients were treated by dentists/orthodontists requiring multiple surgical interventions and orthodontic treatment. Seven patients who had recurrent ear infection underwent ventilation tube insertion. Seven of 11 patients who had obstructive sleep apnea underwent adenotonsillectomy. Four patients underwent orthognathic surgery to correct midface hypoplasia and malocclusion. Two patients had cranioplasty for correction of metopic depressions. The characteristic findings of patients with CCD involving multiple regions of the body should draw clinicians' attention to the need for multidisciplinary management of these patients.
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http://dx.doi.org/10.1097/SCS.0000000000006306DOI Listing
June 2020

Effects of Temperature and Nutrient Supply on Resource Allocation, Photosynthetic Strategy, and Metabolic Rates of Synechococcus sp.

J Phycol 2020 06 26;56(3):818-829. Epub 2020 Mar 26.

Department of Ecology and Animal Biology, Universidade de Vigo, 36310, Vigo, Spain.

Temperature and nutrient supply are key factors that control phytoplankton ecophysiology, but their role is commonly investigated in isolation. Their combined effect on resource allocation, photosynthetic strategy, and metabolism remains poorly understood. To characterize the photosynthetic strategy and resource allocation under different conditions, we analyzed the responses of a marine cyanobacterium (Synechococcus PCC 7002) to multiple combinations of temperature and nutrient supply. We measured the abundance of proteins involved in the dark (RuBisCO, rbcL) and light (Photosystem II, psbA) photosynthetic reactions, the content of chlorophyll a, carbon and nitrogen, and the rates of photosynthesis, respiration, and growth. We found that rbcL and psbA abundance increased with nutrient supply, whereas a temperature-induced increase in psbA occurred only in nutrient-replete treatments. Low temperature and abundant nutrients caused increased RuBisCO abundance, a pattern we observed also in natural phytoplankton assemblages across a wide latitudinal range. Photosynthesis and respiration increased with temperature only under nutrient-sufficient conditions. These results suggest that nutrient supply exerts a stronger effect than temperature upon both photosynthetic protein abundance and metabolic rates in Synechococcus sp. and that the temperature effect on photosynthetic physiology and metabolism is nutrient dependent. The preferential resource allocation into the light instead of the dark reactions of photosynthesis as temperature rises is likely related to the different temperature dependence of dark-reaction enzymatic rates versus photochemistry. These findings contribute to our understanding of the strategies for photosynthetic energy allocation in phytoplankton inhabiting contrasting environments.
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http://dx.doi.org/10.1111/jpy.12983DOI Listing
June 2020

The Effect of Fronto-Orbital Advancement on Frontal Sinus Development and Function in Non-Syndromic and Syndromic Craniosynostosis.

J Craniofac Surg 2020 May/Jun;31(3):707-710

Australian Craniofacial Unit.

The impact of fronto-orbital advancement (FOA) on frontal sinus development and function is anecdotally variable. The aim of this study was to assess the impact of FOA on development of frontal sinuses, and additionally to identify the complications that might arise out of such procedures. This was a retrospective case-control study. Non-syndromic and syndromic craniosynostosis patients (n = 58) who underwent FOA at an early age and also had a skull radiograph or CT scan after the age of 12 were selected. Age matched trauma patients with CT scans done beyond 12 years of age were used as controls. Age at first FOA surgery, total number of procedures and age at imaging was noted. Presence or absence of frontal sinuses was assessed using imaging studies initially. Patients with a formed frontal sinus and a CT scan were further chosen for volumetric studies. Complications related to frontal sinus and secondary surgeries were recorded. One of 27 non-syndromic patients had absent frontal sinuses. Seven of 31 syndromic patients had absent sinuses. Among 20 controls, only 1 patient did not develop frontal sinuses. The mean age at first FOA was 11.81 months and 18.25 months for non-syndromic and syndromic groups, respectively. The average number of procedures before 12 years of age was 1.25 and 1.51 for non-syndromic and syndromic patients, respectively. The mean age at imaging was 17.74, 20.96, and 20.25 years for non-syndromic, syndromic and control groups, respectively. The mean frontal sinus volumes were 13050.36, 15039.02, and 8459.48 mm for non-syndromic, syndromic and control groups, respectively. In conclusion, FOA does not seem to have an impact on rate of pneumatization in the background of similar rates in the non-syndromic and control groups. The low pneumatization rate in syndromic group might be a virtue of the disease itself. There were significant frontal sinus complications that occurred after fronto orbital advancement and this should be borne in mind during the surgical consenting process.
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http://dx.doi.org/10.1097/SCS.0000000000006232DOI Listing
September 2020

The Economic Value of the Delivery of Primary Cleft Surgery in Timor Leste 2000-2017.

World J Surg 2020 06;44(6):1699-1705

Royal Australasian College of Surgeons (RACS), Melbourne, Australia.

Background: Plastic and reconstructive surgical teams visiting from Australia, a high-income country, have delivered cleft surgical services to Timor Leste since 2000 on a volunteer basis. This paper aims to estimate the economic benefit of correcting cleft deformities in this new nation as it evolved its healthcare delivery service from independence in 1999.

Methods: We have utilised a prospective database of all cleft surgical interventions performed during 44 plastic surgical missions over the last 18 years. The disability-adjusted life year (DALY) framework was used to calculate the total DALYs averted by primary cleft lip and palate repair. The 2004 global burden of disease disability weights were used. Economic benefits were calculated using the gross national income (GNI) and the value of a statistical life (VSL) methods for Timor Leste. Estimates were adjusted for treatment effectiveness, counterfactual cases, and complications. Cost estimates included the local hospitalisation costs, the foregone salaries of the visiting surgeons and nurses, other costs associated with providing surgical care, and an estimate for foregone wages of the patients or their carers. Sensitivity analysis was performed with income elasticity set to 0.55, 1.0, and 1.5.

Results: During 44 visiting plastic surgical missions to Timor Leste, 1500 procedures were performed, including 843 primary cleft lip and palate operations. The cleft procedures resulted in the aversion of 842 DALYs and an economic return to Timor Leste of USD 2.2 million (GNI-based) or USD 197,917 (VSL-based). Our programme cost USD 705 per DALY averted. The economic return on investment was 0.3:1 (VSL-based) or 3.8:1 (GNI-based).

Conclusion: A sustained and consistent visiting team approach providing repair of cleft lip and palate defects has resulted in considerable economic gain for Timor Leste over an 18-year period. The training of a local surgeon and multidisciplinary team with ongoing support to the in-country cleft service is expected to reduce the cost per DALY averted once the surgeon and team are able to manage clefts independently.
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http://dx.doi.org/10.1007/s00268-020-05388-3DOI Listing
June 2020

Archaeology and art in context: Excavations at the Gunu Site Complex, Northwest Kimberley, Western Australia.

PLoS One 2020 5;15(2):e0226628. Epub 2020 Feb 5.

Centre for Archaeological Science, University of Wollongong, Wollongong, New South Wales, Australia.

The Kimberley region of Western Australia is one of the largest and most diverse rock art provenances in the world, with a complex stylistic sequence spanning at least 16 ka, culminating in the modern art-making of the Wunumbal people. The Gunu Site Complex, in the remote Mitchell River region of the northwest Kimberley, is one of many local expressions of the Kimberley rock art sequence. Here we report excavations at two sites in this complex: Gunu Rock, a sand sheet adjacent to rock art panels; and Gunu Cave, a floor deposit within an extensive rockshelter. Excavations at Gunu Rock provide evidence for two phases of occupation, the first from 7-8 to 2.7 ka, and the second from 1064 cal BP. Excavations at Gunu Rock provide evidence for occupation from the end of the second phase to the recent past. Stone for tools in the early phase were procured from a variety of sources, but quartz crystal reduction dominated the second occupation phase. Small quartz crystals were reduced by freehand percussion to provide small flake tools and blanks for manufacturing small points called nguni by the Wunambal people today. Quartz crystals were prominent in historic ritual practices associated with the Wanjina belief system. Complex methods of making bifacially-thinned and pressure flaked quartzite projectile points emerged after 2.7 ka. Ochre pigments were common in both occupation phases, but evidence for occupation contemporaneous with the putative age of the oldest rock art styles was not discovered in the excavations. Our results show that developing a complete understanding of rock art production and local occupation patterns requires paired excavations inside and outside of the rockshelters that dominate the Kimberley.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226628PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001911PMC
April 2020

Clinical outcome and explant histology after using a cellular bone allograft in two-stage total hip arthroplasty.

J Orthop Surg Res 2020 Jan 16;15(1):16. Epub 2020 Jan 16.

LifeNet Health, Virginia Beach, VA, USA.

Background: Although use of cellular bone allografts (CBA) in orthopedic surgery has become increasingly common, little information is available regarding their short-term clinical performance. In these two case reports of two-stage hip arthroplasties, ViviGen Formable CBA (V-CBA) was used in stage one to fill voids left by previous metal implants.

Methods: The two patients had distinctly different health profiles, but each of them had previous metal implants due to a hip fracture. In the otherwise healthy 49-year-old male patient, the total hip arthroplasty (THA) was performed 7 weeks after nail removal and V-CBA backfill. In the 64-year-old female patient with Type 1 diabetes and severe osteoporosis, stage 2 was performed after 12 weeks. At the time of THA for each patient, bone containing some V-CBA was removed to accommodate the hip implant. The explants were histologically analyzed for bone matrix, mineralization, and neovascularization.

Results: Histological staining showed substantial new bone formation and neovascularization in both explants albeit at different levels of maturity.

Conclusions: Although limited, these results suggest that V-CBA may facilitate new bone formation in healthy as well as in metabolically challenged patients.

Level Of Evidence: V, case report.
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http://dx.doi.org/10.1186/s13018-020-1542-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966822PMC
January 2020

HYPNOTIC RESPONSIVENESS AND NONHYPNOTIC SUGGESTIBILITY:

Int J Clin Exp Hypn 2020 Jan-Mar;68(1):38-67

Department of Psychology, University of Tennessee, Knoxville, USA.

This study examined if participants respond to different types of suggestions, including hypnosis, uniquely or similarly. This study used 9 suggestibility measures and hypothesized a 3-factor model. It was hypothesized that hypnosis, Chevreul's pendulum, and body-sway would load on the first factor; the odor test, progressive weights, and placebo on the second factor; and conformity, persuasibility, and interrogative suggestibility would load on the third factor. The study comprised 110 college students. Factor analyses failed to result in three factors. Additional attempts at two and three-factor models were also rejected. Hypnosis had no strong relationship with the various suggestibility measures. Thus, no clearly delineated factor structure of suggestibility emerged, indicating that the domain of suggestibility seems to be neither a single attribute, trait, or group of related abilities. Implications are discussed.
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http://dx.doi.org/10.1080/00207144.2020.1685330DOI Listing
January 2021

Last appearance of Homo erectus at Ngandong, Java, 117,000-108,000 years ago.

Nature 2020 01 18;577(7790):381-385. Epub 2019 Dec 18.

Department of Anthropology and Museum of Natural History, University of Iowa, Iowa City, IA, USA.

Homo erectus is the founding early hominin species of Island Southeast Asia, and reached Java (Indonesia) more than 1.5 million years ago. Twelve H. erectus calvaria (skull caps) and two tibiae (lower leg bones) were discovered from a bone bed located about 20 m above the Solo River at Ngandong (Central Java) between 1931 and 1933, and are of the youngest, most-advanced form of H. erectus. Despite the importance of the Ngandong fossils, the relationship between the fossils, terrace fill and ages have been heavily debated. Here, to resolve the age of the Ngandong evidence, we use Bayesian modelling of 52 radiometric age estimates to establish-to our knowledge-the first robust chronology at regional, valley and local scales. We used uranium-series dating of speleothems to constrain regional landscape evolution; luminescence, argon/argon (Ar/Ar) and uranium-series dating to constrain the sequence of terrace evolution; and applied uranium-series and uranium series-electron-spin resonance (US-ESR) dating to non-human fossils to directly date our re-excavation of Ngandong. We show that at least by 500 thousand years ago (ka) the Solo River was diverted into the Kendeng Hills, and that it formed the Solo terrace sequence between 316 and 31 ka and the Ngandong terrace between about 140 and 92 ka. Non-human fossils recovered during the re-excavation of Ngandong date to between 109 and 106 ka (uranium-series minimum) and 134 and 118 ka (US-ESR), with modelled ages of 117 to 108 thousand years (kyr) for the H. erectus bone bed, which accumulated during flood conditions. These results negate the extreme ages that have been proposed for the site and solidify Ngandong as the last known occurrence of this long-lived species.
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http://dx.doi.org/10.1038/s41586-019-1863-2DOI Listing
January 2020

Multilevel instrumented posterolateral lumbar spine fusion with an allogeneic cellular bone graft.

J Orthop Surg Res 2019 Nov 15;14(1):372. Epub 2019 Nov 15.

LifeNet Health, 1864 Concert Drive, Virginia Beach, VA, 23455, USA.

Background: Low back pain (LBP) is the leading cause of absence from work, disability, and impaired quality of life. Fusion surgery may be indicated when non-operative treatments have failed to provide relief. Surgery may include the use of fusion-enhancing implants, such as cellular bone allografts (CBAs). The purpose of this retrospective study was to evaluate efficacy and safety of one CBA (V-CBA) in patients who underwent instrumented posterolateral fusion (IPLF).

Methods: Retrospective data were collected from 150 consecutive patients who had undergone IPLF surgery between January 1, 2015, and March 31, 2018, in which V-CBA was used. All surgeries were performed by one surgeon. V-CBA was mixed with local autograft bone. Patient diagnoses included degenerative disc disease, spondylosis, spondylolisthesis, or spondylolysis with or without stenosis. Standing anteroposterior (AP) and lateral images were collected prior to surgery and again at the terminal visit, which took place between 6 and 33 months post-operatively. De-identified images were assessed radiologically. Adverse events were documented. The primary composite endpoint of fusion status was dependent upon two main criteria: bridging bone per the Lenke scale (classified as "A" definitely solid or "B" possibly solid) and posterior hardware status (intact). Lenke scale C or D were categorized as pseudarthrosis.

Results: Eighty-seven male and 63 female patients (613 levels total) underwent IPLF in which V-CBA was implanted. An average of 4.1 levels was treated, with 59.3% of patients having undergone treatment for more than 3 levels. Twenty-nine percent of patients had diabetes. Fifty-two percent of patients had previously used nicotine products, and 12% were current smokers. Sixteen serious adverse events were recorded and included lumbar seroma, cerebrospinal fluid leak, wound dehiscence, pneumonia, urinary tract infection, and myocardial infarction. Successful fusion (Lenke scale "A" or "B") was recorded in 148 out of 150 patients (98.7%), or 608 out of 613 levels. The total pseudarthrosis rate was 0.8%.

Conclusions: The use of V-CBA combined with local autograft in multilevel IPLF resulted in successful fusions in 98.7% of patients. These results are particularly robust given the complex nature of many of these cases: 89 patients had 4 or more surgical levels, and many patients had multiple comorbidities.

Level Of Evidence: IV.
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http://dx.doi.org/10.1186/s13018-019-1424-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858666PMC
November 2019

Health economics for treatment of diabetic foot ulcers: a cost-effectiveness analysis of eight skin substitutes.

J Wound Care 2019 Sep;28(Sup9):S14-S26

RTI Health Solutions, Research Triangle Park, NC, US.

Aim: Skin substitutes are frequently used to treat chronic diabetic foot ulcers (DFU), and many different options are available. While the clinical efficacy of many products has been evaluated, a comprehensive cost-effectiveness analysis comparing the most popular skin substitutes and using the most recent cost data has been lacking.

Methods: This study compared eight skin substitutes using published efficacy rates combined with the Centers for Medicare and Medicaid Services (CMS) 2018 cost data. The study criteria resulted in the inclusion of seven studies that described efficacy rates for treatment of DFUs using the skin substitutes.

Results: The results revealed wide discrepancies between these skin substitutes for the costs of treatments and healing rates in hospital outpatient departments and physician office settings. Healing rates for 12 and 16 weeks ranged from 28% to 68%, while the average cost for treating one DFU varied from $2001 to $14,507 and $1207 to $8791 in the hospital outpatient department and physician's office setting, respectively. The estimated patient share of costs for treating a single DFU ranged from $400 to $2901 and $241 to $1758 in the hospital outpatient department and physician's office setting, respectively. Most importantly, the estimated number of wounds healed out of 100 DFUs per $1000 expenditure with each patient ranged from 3.9-26.5 DFUs in the hospital outpatient department, and 4.3-36.4 DFUs in the physicians' office setting.

Conclusions: This study revealed that the costs of a skin substitute itself did not necessarily correlate with its healing efficacy. These results provide a comprehensive cost-effectiveness analysis to enable integrated health-care systems, health professionals and reimbursement payers to make informed value decisions when treating DFUs.
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http://dx.doi.org/10.12968/jowc.2019.28.Sup9.S14DOI Listing
September 2019

A Prospective, Multicenter, Single-Arm Clinical Trial for Treatment of Complex Diabetic Foot Ulcers with Deep Exposure Using Acellular Dermal Matrix.

Adv Skin Wound Care 2019 Sep;32(9):409-415

Shawn Cazzell, DPM, FAPWCA, FAPWH, is Chief Medical Officer, Limb Preservation Platform, Fresno, California. Peter M. Moyer, DPM, FACFAS, AAPWCA, is Podiatrist, Purvis Moyer Foot and Ankle Center, Rocky Mount, North Carolina. At LifeNet Health, Virginia Beach, Virginia, Brian Samsell, BS, is Scientific Writer; Kimberly Dorsch, BS, CCRP, CRCP, is Director of Global Clinical Affairs; Julie McLean, PhD, is Senior Manager of Scientific Affairs; and Mark A. Moore, PhD, is Global Senior Director of Scientific Affairs. Acknowledgments: The authors thank Collin Smith for data analysis support. This study was funded by LifeNet Health, a nonprofit organization that processes the studied acellular dermal matrix. Dr Cazzell and Dr Moyer were among the clinical trial investigators for this study and received research funding. Mr Samsell, Ms Dorsch, Dr McLean, and Dr Moore are employees of LifeNet Health. All patient outcomes were evaluated solely by the investigators to minimize potential for bias. The authors have disclosed no other financial relationships related to this article. Submitted January 3, 2019; accepted in revised form March 8, 2019; published online ahead of print, July 9, 2019.

Objective: This prospective, multicenter study evaluated the efficacy and safety of an acellular dermal matrix allograft, DermACELL (D-ADM; LifeNet Health, Virginia Beach, Virginia), in the treatment of large, complex diabetic foot ulcers (DFUs) that probed to tendon or bone.

Methods: Inclusion criteria were Wagner grade 3 or 4 DFUs between 4 weeks and 1 year in duration. All participants received one application of D-ADM at baseline and could receive one additional application if wound healing arrested. Ulcers were assessed weekly for 16 weeks using a laser measuring device.

Results: Sixty-one participants were enrolled, with an average wound area of 29.0 cm; 59 of these ulcers showed exposed bone. The entire per-protocol population (n = 47) achieved 100% granulation. The mean time to 100% granulation was 4.0 weeks with an average of 1.2 applications of D-ADM. Mean percent wound area reduction was 80.3% at 16 weeks. Those DFUs 15 cm or smaller were substantially more likely to close than DFUs larger than 29 cm (P = .0008) over a 16-week duration. No complications were associated with the use of the studied matrix.

Conclusions: The D-ADM demonstrated the ability to rapidly reduce the size of large, complex DFUs with exposed bone. Some wounds did not completely heal by 16 weeks; however, the significant reduction in size suggests that these large, complex wounds may heal if given more time.
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http://dx.doi.org/10.1097/01.ASW.0000569132.38449.c0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328871PMC
September 2019

Surgical Implications of the Anteriorly Displaced Segments of the Anterior Cerebral Artery in the Management of Frontoethmoidal Meningoencephalocele.

J Craniofac Surg 2019 May/Jun;30(3):816-817

Australian Craniofacial Unit, Women's and Children's Hospital, Adelaide, Australia.

Background: Preservation of the anterior cerebral arteries (ACAs) is important in the surgical management of frontoethmoidal meningoencephalocele (FEME). This would avoid complications related to the loss of blood supply to the part of the brain supplied by the ACA. Previous reports have identified hydrocephalus, microcephaly, cerebral dysplasias amounting to a 15% to 20% prevalence of brain anomalies in patients with FEME. What has not been previously reported are cerebral vasculature changes in the frontal region in FEME and how these may impact on the surgical correction and clinical outcome.

Methods: Two patients of FEME that demonstrate cautionary radiologic findings in relation to the ACAs and anterior fossa anatomy are discussed.

Results: The ACA in a 4-year-old boy with FEME was displaced anteriorly with the long A1 segments that extend into the defect. In the 2nd patient, a 4-year-old girl, we report on the complications related to the injury of ACAs from a previously partially resected FEME.

Conclusion: The importance of the anterior cerebral vasculature around the FEME during surgery is crucial to prevent complications resulting from damage to a looping A1 segment of the ACA.
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http://dx.doi.org/10.1097/SCS.0000000000005170DOI Listing
July 2019

Absorbent Microbiopsy Sampling and RNA Extraction for Minimally Invasive, Simultaneous Blood and Skin Analysis.

J Vis Exp 2019 02 21(144). Epub 2019 Feb 21.

Future Industries Institute, University of South Australia; Faculty of Medicine, University of Queensland;

Conventional skin biopsy limits the clinical research that involves cosmetically sensitive areas or pediatric applications due to its invasiveness. Here, we describe the protocol for using an absorbent microneedle-based device, absorbent microbiopsy, for minimally invasive sampling of skin and blood mixture. Our goal is to help facilitate rapid progress in clinical research, the establishment of biomarkers for skin disease and reducing the risk for clinical research participants. In contrast to conventional skin biopsy techniques, the absorbent microbiopsy can be performed within seconds and does not require intensive training due to its simple design. In this report, we describe the use of absorbent microbiopsy, including loading and application, on a volunteer. Then, we show how to isolate RNA from the absorbed sample. Finally, we demonstrate the use of quantitative reverse transcription PCR (RT-qPCR) to quantify mRNA expression levels of both blood (CD3E and CD19) and skin (KRT14 and TYR). The methods that we describe utilize off the shelf kits and reagents. This protocol offers a minimally invasive approach for simultaneous sampling of skin and blood within the same absorbent microbiopsy matrix. We have found human ethics committees, clinicians and volunteers to be supportive of this approach to dermatological research.
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http://dx.doi.org/10.3791/58614DOI Listing
February 2019

Erratum: Author Correction: Identification of genes required for eye development by high-throughput screening of mouse knockouts.

Commun Biol 2019 7;2:97. Epub 2019 Mar 7.

Department of Ophthalmology & Vision Science, School of Medicine, U.C. Davis, Sacramento, CA, 95817, USA.

[This corrects the article DOI: 10.1038/s42003-018-0226-0.].
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http://dx.doi.org/10.1038/s42003-019-0349-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405960PMC
March 2019

Preservation of allograft bone using a glycerol solution: a compilation of original preclinical research.

Biomater Res 2019 13;23. Epub 2019 Feb 13.

LifeNet Health, 1864 Concert Drive, Virginia Beach, VA 23453 USA.

Background: Bone allografts are used in many orthopedic procedures to provide structural stability as well as an osteoconductive matrix for bone ingrowth and fusion. Traditionally, bone allografts have been preserved by either freezing or freeze-drying. Each of these preservation methods has some disadvantages: Frozen grafts require special shipping and storage conditions, and freeze-drying requires special lyophilization equipment and procedures that may impact biomechanical integrity. This report describes an alternate type of preservation using glycerol, which allows storage of fully-hydrated tissues at ambient temperature avoiding the potential complications from freeze-drying.

Methods: In the in vitro three-point bend test, cortical bone was processed and frozen, freeze-dried, or treated with glycerol-based preservation (GBP). Load was applied to each graft at a rate of 2.71 mm/min. The flexural strain, flexural strength, and flexural modulus were then calculated. In the in vitro axial compression test, iliac crest wedges, fibular segments, and Cloward dowels were processed and either freeze-dried or GBP treated. The compressive strength of the grafts were tested at time zero and after real time aging of 1, 4, and 5 years. In the in vivo rat calvarial defect assessment, freeze-dried, frozen, and GBP bone implants were compared after being implanted into a critical sized defect. Samples underwent histological and biomechanical evaluation.

Results: Bone grafts subjected to GBP were found to be at least biomechanically equivalent to frozen bone while also being significantly less brittle than freeze-dried bone. GBP-preserved bone demonstrated significantly greater compressive strength than freeze-dried at multiple time points. Preclinical research performed in calvaric defect models found that GBP-preserved bone had similar osteoconductivity and biocompatibility to frozen and freeze-dried samples.

Conclusion: Preclinical research demonstrated that glycerol-preservation of bone yields a material that maintains biomechanical strength while eliminating the need for extensive rehydration or thaw periods if used clinically. Additionally, in vivo evidence suggests no negative impact of glycerol-preservation on the ability of bone grafts to successfully participate in new bone formation and fusion.
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http://dx.doi.org/10.1186/s40824-019-0154-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373109PMC
February 2019

Identification of genes required for eye development by high-throughput screening of mouse knockouts.

Commun Biol 2018 21;1:236. Epub 2018 Dec 21.

Department of Ophthalmology & Vision Science, School of Medicine, U.C. Davis, Sacramento, CA, 95817, USA.

Despite advances in next generation sequencing technologies, determining the genetic basis of ocular disease remains a major challenge due to the limited access and prohibitive cost of human forward genetics. Thus, less than 4,000 genes currently have available phenotype information for any organ system. Here we report the ophthalmic findings from the International Mouse Phenotyping Consortium, a large-scale functional genetic screen with the goal of generating and phenotyping a null mutant for every mouse gene. Of 4364 genes evaluated, 347 were identified to influence ocular phenotypes, 75% of which are entirely novel in ocular pathology. This discovery greatly increases the current number of genes known to contribute to ophthalmic disease, and it is likely that many of the genes will subsequently prove to be important in human ocular development and disease.
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http://dx.doi.org/10.1038/s42003-018-0226-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303268PMC
December 2018

Cancer and Aging: Reflections for Elders (CARE): A pilot randomized controlled trial of a psychotherapy intervention for older adults with cancer.

Psychooncology 2019 01 7;28(1):39-47. Epub 2018 Nov 7.

Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Objective: Cancer and Aging: Reflections for Elders (CARE) is a novel, telephone-delivered intervention designed to alleviate distress in older cancer patients. This pilot randomized controlled trial tested the feasibility and initial efficacy of CARE, drawing from age-appropriate developmental themes and well-established coping theory.

Method: Eligible patients were ≥70 years old; ≥6 months post-diagnosis of lung, prostate, breast, lymphoma, or gynecological cancer; on active cancer treatment or within 6 months of ending cancer treatment; and had elevated scores on the Distress Thermometer (≥4) or Hospital Anxiety and Depression Scale (≥6). Participants completed five sessions of psychotherapy over 7 weeks with assessments at study entry, post-intervention, and 2 months post-intervention. Primary outcomes were feasibility and initial efficacy on anxiety and depression; secondary outcomes included demoralization, coping, loneliness, and spiritual well-being.

Results: Fifty-nine participants were randomized to either the CARE arm (n = 31) or the enhanced Social Work Control arm (n = 28). The intervention was feasible and tolerable, meeting a priori criteria for rates of eligibility, acceptance, retention, assessment, and treatment fidelity. Upon completion of the intervention, participants in the CARE arm demonstrated lower mean depression scores (d = 0.58 [CI: 0.04-1.12], P = 0.01) and trended towards increased coping-planning (d = 0.30 [CI: -0.83 to 0.24], P = 0.18). Promising trends in anxiety (d = 0.41 [CI: -0.17 to 0.98], P = 0.10) emerged at 2 months post-intervention; effects for coping-planning dissipated.

Conclusion: These pilot data suggest the CARE intervention is feasibly delivered, potentially impacts important psychosocial variables, and is accessible for older, frail patients with cancer. Future research will evaluate this intervention on a larger scale.
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http://dx.doi.org/10.1002/pon.4907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476184PMC
January 2019

Roadmaps and Detours: Active Chlorophyll- a Assessments of Primary Productivity Across Marine and Freshwater Systems.

Environ Sci Technol 2018 11 5;52(21):12039-12054. Epub 2018 Oct 5.

Climate Change Cluster , University of Technology Sydney , Ultimo, Sydney 2007 , New South Wales , Australia.

Assessing phytoplankton productivity over space and time remains a core goal for oceanographers and limnologists. Fast Repetition Rate fluorometry (FRRf) provides a potential means to realize this goal with unprecedented resolution and scale yet has not become the "go-to" method despite high expectations. A major obstacle is difficulty converting electron transfer rates to equivalent rates of C-fixation most relevant for studies of biogeochemical C-fluxes. Such difficulty stems from methodological inconsistencies and our limited understanding of how the electron requirement for C-fixation (Φ) is influenced by the environment and by differences in the composition and physiology of phytoplankton assemblages. We outline a "roadmap" for limiting methodological bias and to develop a more mechanistic understanding of the ecophysiology underlying Φ. We 1) re-evaluate core physiological processes governing how microalgae invest photosynthetic electron transport-derived energy and reductant into stored carbon versus alternative sinks. Then, we 2) outline steps to facilitate broader uptake and exploitation of FRRf, which could transform our knowledge of aquatic primary productivity. We argue it is time to 3) revise our historic methodological focus on carbon as the currency of choice, to 4) better appreciate that electron transport fundamentally drives ecosystem biogeochemistry, modulates cell-to-cell interactions, and ultimately modifies community biomass and structure.
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http://dx.doi.org/10.1021/acs.est.8b03488DOI Listing
November 2018

Structural and functional characterization of IdiA/FutA (Tery_3377), an iron-binding protein from the ocean diazotroph .

J Biol Chem 2018 11 14;293(47):18099-18109. Epub 2018 Sep 14.

the Department of Biological Sciences, Faculty of Natural and Environmental Sciences, Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, United Kingdom, and. Electronic address:

Atmospheric nitrogen fixation by photosynthetic cyanobacteria (diazotrophs) strongly influences oceanic primary production and in turn affects global biogeochemical cycles. Species of the genus are major contributors to marine diazotrophy, accounting for a significant proportion of the fixed nitrogen in tropical and subtropical oceans. However, spp. are metabolically constrained by the availability of iron, an essential element for both the photosynthetic apparatus and the nitrogenase enzyme. Survival strategies in low-iron environments are typically poorly characterized at the molecular level, because these bacteria are recalcitrant to genetic manipulation. Here, we studied a homolog of the iron deficiency-induced A (IdiA)/ferric uptake transporter A (FutA) protein, Tery_3377, which has been used as an iron-stress biomarker. IdiA/FutA has an ambiguous function in cyanobacteria, with its homologs hypothesized to be involved in distinct processes depending on their cellular localization. Using signal sequence fusions to GFP and heterologous expression in the model cyanobacterium sp. PCC 6803, we show that Tery_3377 is targeted to the periplasm by the twin-arginine translocase and can complement the deletion of the native ferric-iron ABC transporter periplasmic binding protein (FutA2). EPR spectroscopy revealed that purified recombinant Tery_3377 has specificity for iron in the Fe state, and an X-ray crystallography-determined structure uncovered a functional iron substrate-binding domain, with Fe pentacoordinated by protein and buffer ligands. Our results support assignment of Tery_3377 as a functional FutA subunit of an Fe ABC transporter but do not rule out dual IdiA function.
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http://dx.doi.org/10.1074/jbc.RA118.001929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254336PMC
November 2018

The Performance of two silica based ion exchange resins in the separation of Bi from its parent solution of Ac.

Appl Radiat Isot 2018 Nov 25;141:68-72. Epub 2018 Aug 25.

University of Tennessee, 1512 Middle Way, Knoxville 37996, TN, USA.

The performance of two inorganic ion exchange resins, Isolute SCX and Isolute SCX-2, were compared to the performance of the organic resin AG-50X8 in the separation of the radionuclide bismuth-213 from its parent solution of actinium-225. The breakthrough of the actinium-225 for all three columns was well below the toxicity level but the Isolute SCX and Isolute SCX-2 produced less of the bismuth-213 available on the column.
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http://dx.doi.org/10.1016/j.apradiso.2018.08.020DOI Listing
November 2018

Rational engineering of photosynthetic electron flux enhances light-powered cytochrome P450 activity.

Synth Biol (Oxf) 2018 22;3(1):ysy009. Epub 2018 Jun 22.

Ocean and Earth Science, University of Southampton, Waterfront Campus, National Oceanography Centre, Southampton SO14 3ZH, UK.

In this study, we exploited a modified photosynthetic electron transfer chain (PET) in the model cyanobacterium PCC 7002, where electrons derived from water-splitting are used to power reactions catalyzed by a heterologous cytochrome P450 (CYP1A1). A simple fluorescent assay for CYP1A1 activity was employed to determine the impact of rationally engineering of photosynthetic electron flow. This showed that knocking out a subunit of the type I NADH dehydrogenase complex (NDH-1), suggested to be involved in cyclic photosynthetic electron flow (Δ), can double the activity of CYP1A1, with a concomitant increase in the flux of electrons from photosynthesis. This also resulted in an increase in cellular adenosine triphosphate (ATP) and the ATP/nicotinamide adenine dinucleotide phosphate (NADPH) ratio, suggesting that expression of a heterologous electron sink in photosynthetic organisms can be used to modify the bioenergetic landscape of the cell. We therefore demonstrate that CYP1A1 is limited by electron supply and that photosynthesis can be re-engineered to increase heterologous P450 activity for the production of high-value bioproducts. The increase in cellular ATP achieved could be harnessed to support metabolically demanding heterologous processes. Furthermore, this experimental system could provide valuable insights into the mechanisms of photosynthesis.
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http://dx.doi.org/10.1093/synbio/ysy009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445785PMC
June 2018

Achilles Tendon Augmented Repair Using Human Acellular Dermal Matrix: A Case Series.

J Foot Ankle Surg 2018 Nov - Dec;57(6):1225-1229. Epub 2018 May 18.

Global Senior Director, Scientific Affairs, LifeNet Health, Virginia Beach, VA.

Achilles tendon ruptures are common in the general population, especially among members of the older demographic occasionally active in sports. Operative treatments provide a lower incidence of rerupture than do nonoperative treatments, although surgical complications remain a concern. The use of a human acellular dermal matrix to augment Achilles tendon repair might reduce the incidence of complications. In the present case series, we describe the outcomes of 9 patients who underwent Achilles tendon repair with acellular dermal matrix augmentation. Functional outcomes were evaluated using the Foot Function Index-Revised long form, and the clinical results were recorded. After a mean average follow-up period of 14.4 (range 12.0 to 20.0) months, the mean Foot Function Index-Revised long form score was 33.0% ± 4.2%. No cases of rerupture or complications that required additional treatment occurred during the observation period. The outcomes we have presented support further evaluation beyond this case series for using a human acellular dermal matrix to augment Achilles tendon repairs.
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http://dx.doi.org/10.1053/j.jfas.2018.03.006DOI Listing
February 2019