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1.
ACS Omega ; 9(13): 14887-14898, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38585113

ABSTRACT

Polylactic acid (PLA) and poly(ethylene terephthalate glycol) (PETG) are popular thermoplastics used in additive manufacturing applications. The mechanical properties of PLA and PETG can be significantly improved by introducing fillers, such as glass and iron nanoparticles (NPs), into the polymer matrix. Molecular dynamics (MD) simulations with the reactive INTERFACE force field were used to predict the mechanical responses of neat PLA/PETG and PLA-glass/iron and PETG-glass/iron nanocomposites with relatively high loadings of glass/iron NPs. We found that the iron and glass NPs significantly increased the elastic moduli of the PLA matrix, while the PETG matrix exhibited modest increases in elastic moduli. This difference in reinforcement ability may be due to the slightly greater attraction between the glass/iron NP and PLA matrix. The NASA Multiscale Analysis Tool was used to predict the mechanical response across a range of volume percent glass/iron filler by using only the neat and highly loaded MD predictions as input. This provides a faster and more efficient approach than creating multiple MD models per volume percent per polymer/filler combination. To validate the micromechanics predictions, experimental samples incorporating hollow glass microspheres (MS) and carbonyl iron particles (CIP) into PLA/PETG were developed and tested for elastic modulus. The CIP produced a larger reinforcement in elastic modulus than the MS, with similar increases in elastic modulus between PLA/CIP and PETG/CIP at 7.77 vol % CIP. The micromechanics-based mechanical predictions compare excellently with the experimental values, validating the integrated micromechanical/MD simulation-based approach.

2.
bioRxiv ; 2023 Jul 03.
Article in English | MEDLINE | ID: mdl-37461525

ABSTRACT

Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). Here, we identify ß-hydroxybutyrate (ßHB), a ketone body, as a regulator of protein solubility in the aging brain. ßHB is a small molecule metabolite which primarily provides an oxidative substrate for ATP during hypoglycemic conditions, and also regulates other cellular processes through covalent and noncovalent protein interactions. We demonstrate ßHB-induced protein insolubility across in vitro, ex vivo, and in vivo mouse systems. This activity is shared by select structurally similar metabolites, is not dependent on covalent protein modification, pH, or solute load, and is observable in mouse brain in vivo after delivery of a ketone ester. Furthermore, this phenotype is selective for pathological proteins such as amyloid-ß, and exogenous ßHB ameliorates pathology in nematode models of amyloid-ß aggregation toxicity. We have generated a comprehensive atlas of the ßHB-induced protein insolublome ex vivo and in vivo using mass spectrometry proteomics, and have identified common protein domains within ßHB target sequences. Finally, we show enrichment of neurodegeneration-related proteins among ßHB targets and the clearance of these targets from mouse brain, likely via ßHB-induced autophagy. Overall, these data indicate a new metabolically regulated mechanism of proteostasis relevant to aging and AD.

3.
J Frailty Aging ; 12(2): 117-125, 2023.
Article in English | MEDLINE | ID: mdl-36946708

ABSTRACT

BACKGROUND: Lower urinary tract symptoms (LUTS) are associated with prevalent frailty and functional impairment, but longitudinal associations remain unexplored. OBJECTIVES: To assess the association of change in phenotypic frailty with concurrent worsening LUTS severity among older men without clinically significant LUTS at baseline. DESIGN: Multicenter, prospective cohort study. SETTING: Population-based. PARTICIPANTS: Participants included community-dwelling men age ≥65 years at enrollment in the Osteoporotic Fractures in Men study. MEASUREMENTS: Data were collected at 4 visits over 7 years. Phenotypic frailty score (range: 0-5) was defined at each visit using adapted Fried criterion and men were categorized at baseline as robust (0), pre-frail (1-2), or frail (3-5). Within-person change in frailty was calculated at each visit as the absolute difference in number of criteria met compared to baseline. LUTS severity was defined using the American Urologic Association Symptom Index (AUASI; range: 0-35) and men with AUASI ≥8 at baseline were excluded. Linear mixed effects models were adjusted for demographics, health-behaviors, and comorbidities to quantify the association between within-person change in frailty and AUASI. RESULTS: Among 3235 men included in analysis, 48% were robust, 45% were pre-frail, and 7% were frail. Whereas baseline frailty status was not associated with change in LUTS severity, within-person increases in frailty were associated with greater LUTS severity (quadratic P<0.001). Among robust men at baseline, mean predicted AUASI during follow-up was 4.2 (95% CI 3.9, 4.5) among those meeting 0 frailty criteria, 4.6 (95% CI 4.3, 4.9) among those meeting 1 criterion increasing non-linearly to 11.2 (95% CI 9.8, 12.6) among those meeting 5 criteria. CONCLUSIONS: Greater phenotypic frailty was associated with non-linear increases in LUTS severity in older men over time, independent of age and comorbidities. Results suggest LUTS and frailty share an underlying mechanism that is not targeted by existing LUTS interventions.


Subject(s)
Frailty , Lower Urinary Tract Symptoms , Aged , Humans , Male , Frailty/diagnosis , Frailty/epidemiology , Lower Urinary Tract Symptoms/diagnosis , Lower Urinary Tract Symptoms/epidemiology , Prospective Studies , Sarcopenia , Prostatic Hyperplasia
5.
Orphanet J Rare Dis ; 18(1): 33, 2023 02 22.
Article in English | MEDLINE | ID: mdl-36814255

ABSTRACT

BACKGROUND: Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking. OBJECTIVES: We conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae. METHODS: Participants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method. RESULTS: Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index < 1). Among them, 50 statements were agreed upon as 'appropriate'; four statements were considered 'uncertain', and ultimately finally discarded. CONCLUSIONS: Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN.


Subject(s)
Stevens-Johnson Syndrome , Humans , Stevens-Johnson Syndrome/complications , Consensus , Skin , Disease Progression
6.
J Med Microbiol ; 71(3)2022 Mar.
Article in English | MEDLINE | ID: mdl-35275806

ABSTRACT

Introduction. P. aeruginosa is an opportunistic Gram-negative pathogen frequently isolated in urinary tract infections (UTI) affecting elderly and catheterized patients and associated with ineffective antibiotic treatment and poor clinical outcomes.Gap statement. Invasion has been shown to play an important role in UTI caused by E. coli but has only recently been studied with P. aeruginosa. The ability of P. aeruginosa to adapt and evolve in chronic lung infections is associated with resistance to antibiotics but has rarely been studied in P. aeruginosa UTI populations.Aim. We sought to determine whether phenotypic and genotypic heterogeneity exists in P. aeruginosa UTI isolates and whether, like urinary pathogenic Escherichia coli, these could invade human bladder epithelial cells - two factors that could complicate antibiotic treatment.Methodology. P. aeruginosa UTI samples were obtained from five elderly patients at the Royal Liverpool University Hospital as part of routine diagnostics. Fourty isolates from each patient sample were screened for a range of phenotypes. The most phenotypically diverse isolates were genome sequenced. Gentamicin protection assays and confocal microscopy were used to determine capacity to invade bladder epithelial cells.Results. Despite significant within-patient phenotypic differences, no UTI patient was colonized by distinct strains of P. aeruginosa. Limited genotypic differences were identified in the form of non-synonymous SNPs. Gentamicin protection assays and confocal microscopy provided evidence of P. aeruginosa's ability to invade bladder epithelial cells.Conclusions. Phenotypic variation and cell invasion could further complicate antibiotic treatment in some patients. More work is needed to better understand P. aeruginosa UTI pathogenesis and develop more effective treatment strategies.


Subject(s)
Pseudomonas Infections , Urinary Tract Infections , Aged , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Escherichia coli/genetics , Humans , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/genetics , Urinary Tract Infections/drug therapy
8.
Sci Rep ; 12(1): 231, 2022 01 07.
Article in English | MEDLINE | ID: mdl-34997076

ABSTRACT

The inter-cattle growth variations stem from the interaction of many metabolic processes making animal selection difficult. We hypothesized that growth could be predicted using metabolomics. Urinary biomarkers of cattle feed efficiency were explored using mass spectrometry-based untargeted and targeted metabolomics. Feed intake and weight-gain was measured in steers (n = 75) on forage-based growing rations (stage-1, 84 days) followed by high-concentrate finishing rations (stage-2, 84 days). Urine from days 0, 21, 42, 63, and 83 in each stage were analyzed from steers with the greater (n = 14) and least (n = 14) average-daily-gain (ADG) and comparable dry-matter-intake (DMI; within 0.32 SD of the mean). Steers were slaughtered after stage-2. Adjusted fat-thickness and carcass-yield-grade increased in greater-ADG-cattle selected in stage-1, but carcass traits did not differ between ADG-selected in stage-2. Overall 85 untargeted metabolites segregated greater- and least-ADG animals, with overlap across diets (both stages) and breed type, despite sampling time effects. Total 18-bile acids (BAs) and 5-steroids were quantified and associated with performance and carcass quality across ADG-classification depending on the stage. Stepwise logistic regression of urinary BA and steroids had > 90% accuracy identifying efficient-ADG-steers. Urine metabolomics provides new insight into the physiological mechanisms and potential biomarkers for feed efficiency.


Subject(s)
Biomarkers/urine , Cattle/growth & development , Meat/analysis , Animal Feed/analysis , Animals , Bile Acids and Salts/urine , Body Weight , Cattle/urine , Eating , Male , Metabolomics , Steroids/urine
9.
Front Endocrinol (Lausanne) ; 13: 1095189, 2022.
Article in English | MEDLINE | ID: mdl-36619573

ABSTRACT

Context: The recent American and European guidelines on management of patients with primary hyperparathyroidism (PHPT) did not endorse neurocognitive evaluation as part of standard work-up and did not consider it as a surgery criterion.The neurocognitive deleterious effects of hyperparathyroidism and impact of parathyroidectomy on PHPT patients is yet to be elucidated. Objective: To evaluate specific neurocognitive functions in PHPT patients prior to parathyroidectomy and describe the changes during follow-up with serial evaluations. Design: A prospective case-control study including parathyroidectomy candidates evaluated at a tertiary teaching university hospital. Thorough neurocognitive evaluation was conducted before and 1- & 6-months following parathyroidectomy: Rey Auditory Verbal Learning Test (RAVLT), Rey-Osterrieth Complex Figure Test (ROCF), Trail Making Test A, Trail Making Test B, Addenbrooke's Cognitive Examination-III (ACE), Frontal Assessment Battery (FAB), Beck Depression Inventory (BDI). Results: 18 consecutive patients underwent successful parathyroidectomy. Various neurocognitive functions improved significantly after successful parathyroidectomy: long term auditory memory (RAVLT, p=0.008), short- and long-term visual memory (ROCF, p=0.006 and p=0.002 respectively), visual attention and complex concentration skills (trail making A, p<0.001) and executive abilities (trail making B, p=0.005). No change was identified in frontal-lobe abilities. Depression symptoms were absent or minimal prior to surgery and no significant change was observed after surgery. Conclusions: PHPT is associated with significant various neurocognitive dysfunctions when mindfully evaluated before surgery. Successful parathyroidectomy results in several neurocognitive aspect improvements. The data suggest that neurocognitive deterioration may be considered an added parathyroidectomy criterion when surgical decision is not straightforward.


Subject(s)
Hyperparathyroidism, Primary , Parathyroidectomy , Humans , Prospective Studies , Parathyroidectomy/methods , Hyperparathyroidism, Primary/complications , Hyperparathyroidism, Primary/surgery , Hyperparathyroidism, Primary/psychology , Case-Control Studies , Cognition , Hospitals
10.
Int J Oral Maxillofac Surg ; 51(1): 10-17, 2022 Jan.
Article in English | MEDLINE | ID: mdl-33840565

ABSTRACT

The wealth of data in the National Cancer Database (NCDB) has allowed numerous studies investigating patient, disease, and treatment-related factors in oral cavity squamous cell carcinoma (OCSCC); however, to date, no summation of these studies has been performed. The aim of this study was to provide a concise review of the NCDB studies on OCSCC, with the hopes of providing a framework for future, novel studies aimed at enhancing our understanding of clinical parameters related to OCSCC. Two databases were searched, and 27 studies published between 2002 and 2020 were included. The average sample size was 13,776 patients (range 356-50,896 patients). Four areas of research focus were identified: demographic and socioeconomic status, diagnosis, prognosis, and treatment. This review highlights the impact of age, sex, ethnicity, and socioeconomic status on the prognosis and management of OCSCC, describes the prognostic factors, and details the modalities and indications for neck dissection and adjuvant therapy in OCSCC. In conclusion, the NCDB is a very valuable resource for clinicians and researchers involved in the management of OCSCC, offering an incomparable perspective on a large dataset of patients. Future developments regarding hospital information management, review of data accuracy and completeness, and wider accessibility will help clinicians to improve the care of patients affected by OCSCC.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Carcinoma, Squamous Cell/pathology , Humans , Mouth Neoplasms/pathology , Neck Dissection , Neoplasm Staging , Prognosis , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck
11.
Article in English | MEDLINE | ID: mdl-34500309

ABSTRACT

Lipid bioactivity is a result of direct action and the action of lipid mediators including oxylipins, endocannabinoids, bile acids and steroids. Understanding the factors contributing to biological variation in lipid mediators may inform future approaches to understand and treat complex metabolic diseases. This research aims to determine the contribution of genetic and environmental influences on lipid mediators involved in the regulation of inflammation and energy metabolism. This study recruited 138 monozygotic (MZ) and dizygotic (DZ) twins aged 18-65 years and measured serum oxylipins, endocannabinoids, bile acids and steroids using liquid chromatography mass-spectrometry (LC-MS). In this classic twin design, the similarities and differences between MZ and DZ twins are modelled to estimate the contribution of genetic and environmental influences to variation in lipid mediators. Heritable lipid mediators included the 12-lipoxygenase products 12-hydroxyeicosatetraenoic acid [0.70 (95% CI: 0.12,0.82)], 12-hydroxyeicosatetraenoic acid [0.73 (95% CI: 0.30,0.83)] and 14­hydroxy-docosahexaenoic acid [0.51 (95% CI: 0.07,0.71)], along with the endocannabinoid docosahexaenoy-lethanolamide [0.52 (95% CI: 0.15,0.72)]. For others such as 13-hydroxyoctadecatrienoic acid and lithocholic acid the contribution of environment to variation was stronger. With increased understanding of lipid mediator functions in health, it is important to understand the factors contributing to their variance. This study provides a comprehensive analysis of lipid mediators and extends pre-existing knowledge of the genetic and environmental influences on the human lipidome.


Subject(s)
Bile Acids and Salts/blood , Endocannabinoids/blood , Fatty Acids, Omega-3/blood , Lipid Metabolism/genetics , Oxylipins/blood , Steroids/blood , 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid/blood , 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid/genetics , Adolescent , Adult , Aged , Bile Acids and Salts/genetics , Dehydroepiandrosterone/blood , Dehydroepiandrosterone/genetics , Docosahexaenoic Acids/blood , Docosahexaenoic Acids/genetics , Eicosapentaenoic Acid/analogs & derivatives , Eicosapentaenoic Acid/blood , Eicosapentaenoic Acid/genetics , Endocannabinoids/genetics , Fatty Acids, Omega-3/genetics , Female , Gene-Environment Interaction , Humans , Male , Middle Aged , Twins, Dizygotic/genetics , Twins, Monozygotic/genetics , Young Adult
13.
Br J Dermatol ; 185(3): 616-626, 2021 09.
Article in English | MEDLINE | ID: mdl-33657677

ABSTRACT

BACKGROUND: Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. OBJECTIVES: Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. METHODS: Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. RESULTS: Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. CONCLUSIONS: We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.


Subject(s)
Stevens-Johnson Syndrome , Adult , Child , Consensus , Humans , Research , Retrospective Studies , Stevens-Johnson Syndrome/diagnosis , Stevens-Johnson Syndrome/therapy
14.
Chaos ; 31(12): 123129, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34972346

ABSTRACT

We introduce a new mathematical framework for the qualitative analysis of dynamical stability, designed particularly for finite-time processes subject to slow-timescale external influences. In particular, our approach is to treat finite-time dynamical systems in terms of a slow-fast formalism in which the slow time only exists in a bounded interval, and consider stability in the singular limit. Applying this to one-dimensional phase dynamics, we provide stability definitions somewhat analogous to the classical infinite-time definitions associated with Aleksandr Lyapunov. With this, we mathematically formalize and generalize a phase-stabilization phenomenon previously described in the physics literature for which the classical stability definitions are inapplicable and instead our new framework is required.

15.
Neurotoxicology ; 82: 146-157, 2021 01.
Article in English | MEDLINE | ID: mdl-33309840

ABSTRACT

Bisphenol A (BPA) is a ubiquitous environmental chemical that has been linked to behavioral differences in children and shown to impact critical neurodevelopmental processes in animal models. Though data is emerging, we still have an incomplete picture of how BPA disrupts neurodevelopment; in particular, how its impacts may vary across different genetic backgrounds. Given the genetic tractability of Drosophila melanogaster, they present a valuable model to address this question. Fruit flies are increasingly being used for assessment of neurotoxicants because of their relatively simple brain structure and variety of measurable behaviors. Here we investigated the neurodevelopmental impacts of BPA across two genetic strains of Drosophila-w1118 (control) and the Fragile X Syndrome (FXS) model-by examining both behavioral and neuronal phenotypes. We show that BPA induces hyperactivity in larvae, increases repetitive grooming behavior in adults, reduces courtship behavior, impairs axon guidance in the mushroom body, and disrupts neural stem cell development in the w1118 genetic strain. Remarkably, for every behavioral and neuronal phenotype examined, the impact of BPA in FXS flies was either insignificant or contrasted with the phenotypes observed in the w1118 strain. This data indicates that the neurodevelopmental impacts of BPA can vary widely depending on genetic background and suggests BPA may elicit a gene-environment interaction with Drosophila fragile X mental retardation 1 (dFmr1)-the ortholog of human FMR1, which causes Fragile X Syndrome and is associated with autism spectrum disorder.


Subject(s)
Benzhydryl Compounds/toxicity , Drosophila melanogaster/drug effects , Nervous System/drug effects , Phenols/toxicity , Animals , Courtship , Disease Models, Animal , Drosophila melanogaster/genetics , Drosophila melanogaster/growth & development , Female , Fragile X Syndrome/genetics , Fragile X Syndrome/veterinary , Grooming/drug effects , Larva/drug effects , Larva/physiology , Locomotion/drug effects , Male , Nervous System/growth & development
16.
Ophthalmology ; 127(10): 1345-1359, 2020 10.
Article in English | MEDLINE | ID: mdl-32344075

ABSTRACT

PURPOSE: To evaluate features and outcomes of eyes with retinal vasculitis and intraocular inflammation (IOI) after intravitreal injection (IVI) of brolucizumab 6 mg/0.05 ml for treatment of neovascular age-related macular degeneration. DESIGN: Retrospective case series. PARTICIPANTS: Fifteen eyes from 12 patients identified from 10 United States centers. METHODS: Review of patient demographics, ophthalmologic examination results, and retinal imaging findings. MAIN OUTCOME MEASURES: Baseline and follow-up visual acuity (VA), prior anti-vascular endothelial growth factor (VEGF) injections, clinical presentation, retinal findings, fluorescein angiography results, and treatment strategies. RESULTS: The number of previous anti-VEGF IVIs ranged between 2 and 80 in the affected eye before switching to brolucizumab. Retinal vasculitis and IOI were diagnosed at a mean of 30 days after brolucizumab IVI. Mean VA before brolucizumab IVI was 0.426 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/53) and VA at diagnosis of retinal vasculitis was 0.981 logMAR (Snellen equivalent, 20/191; range, 20/25-20/1600; P = 0.008). All affected eyes showed IOI with variable combinations of focal or elongated segmental sheathing and discontinuity of small and large retinal arteries, sclerotic arteries, regions of vascular nonperfusion, cotton-wool spots, Kyrieleis plaques, irregular venous caliber with dilated and sclerotic segments, perivenular hemorrhages, and foci of phlebitis. Fluorescein angiography revealed delayed retinal arterial filling, retinal vascular nonperfusion, and variable dye leakage from affected vessels and the optic nerve. Systemic evaluation for embolic causes was unrevealing in 2 patients, and 3 patients showed negative laboratory assessment for uveitis. Treatment consisted of various combinations of corticosteroids (systemic, intravitreal, and topical), and 2 eyes underwent vitrectomy without improvement in vision. After a mean follow-up of 25 days, mean VA was 0.833 logMAR (Snellen equivalent, 20/136), which was reduced compared with baseline (P = 0.033). CONCLUSIONS: Retinal vasculitis and IOI after brolucizumab IVI are characterized by variable occlusion of large or small retinal arteries, or both, and perivenular abnormalities. It may span from peripheral vasculitis to occlusion of large retinal arteries around the optic nerve or macula with severe vision loss. A high index of suspicion is required because vitreous cells may obscure visualization of retinal details.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Retinal Vasculitis/chemically induced , Uveitis/chemically induced , Visual Acuity , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Female , Fluorescein Angiography , Follow-Up Studies , Fundus Oculi , Humans , Intravitreal Injections , Macula Lutea/pathology , Male , Prognosis , Retinal Vasculitis/diagnosis , Retrospective Studies , Tomography, Optical Coherence , Uveitis/diagnosis
17.
J Hosp Infect ; 103(4): 412-419, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31493477

ABSTRACT

BACKGROUND: Active warming during surgery prevents perioperative hypothermia but the effectiveness and postoperative infection rates may differ between warming technologies. AIM: To establish the recruitment and data management strategies needed for a full trial comparing postoperative infection rates associated with forced air warming (FAW) versus resistive fabric warming (RFW) in patients aged >65 years undergoing hemiarthroplasty following fractured neck of femur. METHODS: Participants were randomized 1:1 in permuted blocks to FAW or RFW. Hypothermia was defined as a temperature of <36°C at the end of surgery. Primary outcomes were the number of participants recruited and the number with definitive deep surgical site infections. FINDINGS: A total of 515 participants were randomized at six sites over a period of 18 months. Follow-up was completed for 70.1%. Thirty-seven participants were hypothermic (7.5% in the FAW group; 9.7% in the RFW group). The mean temperatures before anaesthesia and at the end of surgery were similar. For the primary clinical outcome, there were four deep surgical site infections in the FAW group and three in the RFW group. All participants who developed a postoperative infection had antibiotic prophylaxis, a cemented prosthesis, and were operated under laminar airflow; none was hypothermic. There were no serious adverse events related to warming. CONCLUSION: Surgical site infections were identified in both groups. Progression from the pilot to the full trial is possible but will need to take account of the high attrition rate.


Subject(s)
Heating/methods , Hemiarthroplasty/methods , Hypothermia/prevention & control , Surgical Wound Infection/prevention & control , Aged , Aged, 80 and over , Female , Fractures, Bone/surgery , Humans , Male , Treatment Outcome
19.
Bone Joint J ; 100-B(7): 875-881, 2018 07.
Article in English | MEDLINE | ID: mdl-29954205

ABSTRACT

Aims: This study compared multiple sclerosis (MS) patients who underwent primary total hip arthroplasty (THA) with a matched cohort. Specifically, we evaluated: 1) implant survivorship; 2) functional outcomes (modified Harris Hip Scores (mHHS), Hip Disability and Osteoarthritis Outcome Score, Joint Replacement (HOOS JR), and modified Multiple Sclerosis Impact Scale (mMSIS) scores (with the MS cohort also evaluated based on the disease phenotype)); 3) physical therapy duration and return to function; 4) radiographic outcomes; and 5) complications. Patients and Methods: We reviewed our institution's database to identify MS patients who underwent THA between January 2008 and June 2016. A total of 34 MS patients (41 hips) were matched in a 1:2 ratio to a cohort of THA patients who did not have MS, based on age, body mass index (BMI), and Charlson/Deyo score. Patient records were reviewed for complications, and their functional outcomes and radiographs were reviewed at their most recent follow-up. Results: Compared with the matched cohort, MS patients had lower all-cause implant survivorship at eight years (91.5% (95% confidence interval (CI) 82.7 to 100) vs 98.7% (95% CI 96.2 to 100)) (p = 0.033), lower mHHS scores (66 vs 80, p < 0.001), and HOOS JR scores (79 vs 88, p = 0.009). Multiple sclerosis patients also required more physiotherapy (five weeks vs three weeks, p = 0.002) and took longer to return to baseline (seven weeks vs five weeks, p = 0.010) than the matched cohort. Furthermore, MS patients had more complications than the non-MS patients (six vs zero, p < 0.001). The worse outcomes of the MS group can potentially be explained by predisposition of these patients to mechanical complications and progression of their disease during the period of this study, as demonstrated by worsening of the mMSIS scores (2.9 vs 3.4; p = 0.008). Conclusion: MS patients had lower implant survivorship, lower functional outcome scores, and increased complication rates; in addition, MS patients took longer to return to their baseline functional level after THA. Cite this article: Bone Joint J 2018;100-B:875-81.


Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Hip Prosthesis/adverse effects , Multiple Sclerosis/surgery , Adult , Aged , Aged, 80 and over , Female , Hip Joint/surgery , Humans , Male , Middle Aged , Multiple Sclerosis/complications , Physical Therapy Modalities/statistics & numerical data , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prosthesis Failure , Reoperation/statistics & numerical data , Survival Analysis , Treatment Outcome
20.
AJNR Am J Neuroradiol ; 39(7): 1222-1225, 2018 07.
Article in English | MEDLINE | ID: mdl-29794235

ABSTRACT

BACKGROUND AND PURPOSE: Cerebral microhemorrhages are a known marker of mild traumatic brain injury. Blast-related mild traumatic brain injury relates to a propagating pressure wave, and there is evidence that the mechanism of injury in blast-related mild traumatic brain injury may be different from that in blunt head trauma. Two recent reports in mixed cohorts of blunt and blast-related traumatic brain injury in military personnel suggest that the prevalence of cerebral microhemorrhages is lower than in civilian head injury. In this study, we aimed to characterize the prevalence of cerebral microhemorrhages in military service members specifically with chronic blast-related mild traumatic brain injury. MATERIALS AND METHODS: Participants were prospectively recruited and underwent 3T MR imaging. Susceptibility-weighted images were assessed by 2 neuroradiologists independently for the presence of cerebral microhemorrhages. RESULTS: Our cohort included 146 veterans (132 men) who experienced remote blast-related mild traumatic brain injury (mean, 9.4 years; median, 9 years after injury). Twenty-one (14.4%) reported loss of consciousness for <30 minutes. Seventy-seven subjects (52.7%) had 1 episode of blast-related mild traumatic brain injury; 41 (28.1%) had 2 episodes; and 28 (19.2%) had >2 episodes. No cerebral microhemorrhages were identified in any subject, as opposed to the frequency of SWI-detectable cerebral microhemorrhages following blunt-related mild traumatic brain injury in the civilian population, which has been reported to be as high as 28% in the acute and subacute stages. CONCLUSIONS: Our results may reflect differences in pathophysiology and the mechanism of injury between blast- and blunt-related mild traumatic brain injury. Additionally, the chronicity of injury may play a role in the detection of cerebral microhemorrhages.


Subject(s)
Blast Injuries/complications , Brain Concussion/etiology , Cerebral Hemorrhage/epidemiology , Cerebral Hemorrhage/etiology , Adult , Aged , Blast Injuries/diagnostic imaging , Brain Concussion/diagnostic imaging , Cerebral Hemorrhage/diagnostic imaging , Cohort Studies , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Military Personnel , Prevalence , Young Adult
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