Publications by authors named "Michael Kelly"

894 Publications

A qualitative exploration of the mechanisms, pathways and public health outcomes of a city centre 20mph speed limit intervention: The case of Belfast, United Kingdom.

Health Place 2021 Jul 20;70:102627. Epub 2021 Jul 20.

Centre for Public Health, School of Medicine Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom. Electronic address:

Twenty miles per hour (mph) speed limits can impact the health of the public (e.g., road safety, active travel). However, a better understanding of how individuals experience 20mph limits is required, to ensure interventions are cognisant of perceptions and potential un/intended outcomes. Focus groups (n = 9, 60 participants) to explore the Belfast 20mph intervention highlighted divergent perspectives and experiences including: 12 mechanisms (e.g., limited awareness), 15 pathways (e.g., reduced driving speed→improved liveability) and 10 public health outcomes (e.g., increased cyclist safety). Future interventions should consider un/intended outcomes and implement strategies to enhance effectiveness and mitigate harms (e.g., through training, enforcement).
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http://dx.doi.org/10.1016/j.healthplace.2021.102627DOI Listing
July 2021

Stratifying outcome based on the Oswestry Disability Index for operative treatment of adult spinal deformity on patients 60 years of age or older: A multicenter, multi-continental study on Prospective Evaluation of Elderly Deformity Surgery (PEEDS).

Spine J 2021 Jul 14. Epub 2021 Jul 14.

Department of Neurosurgery and Orthopaedic Surgery, University of California, San Francisco, CA, USA.

Background Context: Patients with adult spinal deformity suffer from disease related disability as measured by the ODI for which surgery can result in significant improvements.

Purpose: The purpose of this study was to show the change in overall and individual components of the Oswestry Disability Index (ODI) in patients aged 60 years or older following multi-level spinal deformity surgery.

Study Design: Prospective, multicenter, multi-continental, observational longitudinal cohort study Patient Sample: Patients ≥60 years undergoing primary spinal fusion surgery of ≥5 levels for coronal, sagittal or combined deformity.

Outcome Measures: Oswestry Disability Index (ODI) Methods: Patients completed the ODI pre-operatively for baseline, then at 10 weeks, 12 months and 24 months post-operatively. ODI scores were grouped into deciles, and change was calculated with numerical score and improvement or worsening was further categorized from baseline as substantial (≥20%), marginal (≥10 - <20%) or no change (within 10%).

Results: Two-hundred nineteen patients met inclusion criteria for the study. The median number of spinal levels fused was 9 [Q1 = 5.0, Q3 = 12.0]. 2-year mean (95% CI) ODI improvement was 19.3% (16.7%; 21.9%; p < 0.001) for all age groups, with mean scores improved from a baseline of 46.3% (44.1%; 48.4%) to 41.1% (38.5%; 43.6%) at 10 weeks (p < 0.001), 28.1% (25.6%; 30.6%) at 12 months (p < 0.001), and 27.0% (24.4%; 29.5%) at 24 months (p < 0.001). At 2 years, 45.5% of patients showed 20% or greater improvement in ODI, 23.7% improved between 10% and 20%, 26.3% reported no change (defined as ±10% from baseline), 4.5% of patients reported a worsening between 10-20%, and none reported worsening greater than 20%. 59.0% of patients were severely disabled (ODI >40%) pre-operatively, which decreased to 20.2% at 2 years. Significant improvement was observed across all 10 ODI items at 12 and 24 months. The largest improvements were seen in pain, walking, standing, sex life, social life and traveling.

Conclusions: In this prospective, multicenter, multi-continental study of patients 60 years or older undergoing multi-level spinal deformity surgery, almost 70% of patients reported significant improvements in ODI without taking into account surgical indications, techniques or complications. Clear data is presented demonstrating the particular change from baseline for each decile of pre-operative ODI score, for each sub-score, and for each age group.
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http://dx.doi.org/10.1016/j.spinee.2021.07.007DOI Listing
July 2021

Beyond Sedlis-A novel histology-specific nomogram for predicting cervical cancer recurrence risk: An NRG/GOG ancillary analysis.

Gynecol Oncol 2021 Jun 30. Epub 2021 Jun 30.

Johns Hopkins University School of Medicine, Baltimore, MD, United States of America. Electronic address:

Purpose: The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment.

Methods: We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk.

Results: We identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12-2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67-4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81-10.26; deep 1/3, HR 7.05, CI 2.99-16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25-17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI.

Conclusions: Current treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer.
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http://dx.doi.org/10.1016/j.ygyno.2021.06.017DOI Listing
June 2021

Single-cell atlas of tumor cell evolution in response to therapy in hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

J Hepatol 2021 Jun 30. Epub 2021 Jun 30.

Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892; Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892. Electronic address:

Background & Aims: Intratumor molecular heterogeneity is a key feature of tumorigenesis and is linked to treatment failure and patient prognosis. Here, we aimed to determine what drives tumor cell evolution by performing single-cell transcriptomic analysis.

Methods: We analyzed 46 hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) biopsies from 37 patients enrolled for interventional studies at the NIH Clinical Center, with 16 biopsies collected before and after treatment from 7 patients. We developed a novel machine learning-based consensus clustering approach to track cellular states of 57,000 malignant and non-malignant cells including tumor cell transcriptome-based functional clonality analysis. We determined tumor cell relationships using RNA velocity and reverse graph embedding. We also studied longitudinal samples from 4 patients to determine tumor cellular state and its evolution. We validated our findings in bulk transcriptomic data from 488 patients with HCC and 277 patients with iCCA.

Results: Using transcriptomic clusters as a surrogate for functional clonality, we observed an increase in tumor cell state heterogeneity which was tightly linked to patient prognosis. Furthermore, increased functional clonality was accompanied by a polarized immune cell landscape which included an increase in pre-exhausted T-cells. We found that SPP1 expression was tightly associated with tumor cell evolution and microenvironmental reprogramming. Finally, we developed a user-friendly online interface as a knowledge base for a single-cell atlas of liver cancer.

Conclusions: Our study offers insight into the collective behavior of tumor cell communities in liver cancer as well as potential drivers of tumor evolution in response to therapy.

Lay Summary: Intratumor molecular heterogeneity is a key feature of tumorigenesis, and is linked to treatment failure and patient prognosis. In this study, we present a single-cell atlas of liver tumors from patients treated with immunotherapy and describe intratumoral cell states and their hierarchical relationship. We suggest osteopontin, encoded by the gene SPP1, as a candidate regulator of tumor evolution in response to treatment.
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http://dx.doi.org/10.1016/j.jhep.2021.06.028DOI Listing
June 2021

Development of a library of laminin-mimetic peptide hydrogels for control of nucleus pulposus cell behaviors.

J Tissue Eng 2021 Jan-Dec;12:20417314211021220. Epub 2021 Jun 8.

Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA.

The nucleus pulposus (NP) of the intervertebral disc plays a critical role in distributing mechanical loads to the axial skeleton. Alterations in NP cells and, consequently, NP matrix are some of the earliest changes in the development of disc degeneration. Previous studies demonstrated a role for laminin-presenting biomaterials in promoting a healthy phenotype for human NP cells from degenerated tissue. Here we investigate the use of laminin-mimetic peptides presented individually or in combination on a poly(ethylene) glycol hydrogel as a platform to modulate the behaviors of degenerative human NP cells. Data confirm that NP cells attach to select laminin-mimetic peptides that results in cell signaling downstream of integrin and syndecan binding. Furthermore, the peptide-functionalized hydrogels demonstrate an ability to promote cell behaviors that mimic that of full-length laminins. These results identify a set of peptides that can be used to regulate NP cell behaviors toward a regenerative engineering strategy.
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http://dx.doi.org/10.1177/20417314211021220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211742PMC
June 2021

Endothelial Recovery in Bare Metal Stents and Drug-Eluting Stents on a Single-Cell Level.

Arterioscler Thromb Vasc Biol 2021 Aug 24;41(8):2277-2292. Epub 2021 Jun 24.

CVPath Institute, Gaithersburg, MD (A.C., L.G., R.F., C.J., S.K., A.S., H.J., Y.S., K.H.P., F.D.K., M.E.R., D.S., R.V., A.V.F.).

[Figure: see text].
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http://dx.doi.org/10.1161/ATVBAHA.121.316472DOI Listing
August 2021

Comparison of Cost and Complication Rates for Profiling Hospital Performance in Lumbar Fusion for Spondylolisthesis.

Spine J 2021 Jun 20. Epub 2021 Jun 20.

Departments of Neurological Surgery.

Background Context: There is growing interest among payers in profiling hospital value and quality-of-care, including both the cost and safety of common surgeries, such as lumbar fusion. Nonetheless, there is sparse evidence describing the statistical reliability of such measures when applied to lumbar fusion for spondylolisthesis.

Purpose: To evaluate the reliability of 90-day inpatient hospital costs, overall complications, and rates of serious complications for profiling hospital performance in lumbar fusion surgery for spondylolisthesis.

Study Design/setting: Data for this analysis came from State Inpatient Databases from nine states made available through the Healthcare Cost and Utilization Project.

Patient Sample: Patients undergoing elective lumbar spine fusion for spondylolisthesis from 2010-2017 in participating states.

Outcome Measures: Statistical reliability, defined as the ability to distinguish true performance differences across hospitals relative to statistical noise. Reliability was assessed separately for 90-day inpatient costs (standardized across years to 2019 dollars), overall complications, and serious complication rates.

Methods: Statistical reliability was measured as the amount of variation between hospitals relative to the total amount of variation for each measure. Total variation includes both between-hospital variation ("signal") and within-hospital variation ("statistical noise"). Thus, reliability equals signal over (signal plus noise) and ranges from 0 to 1. To adjust for differences in patient-level risk and procedural characteristics, hierarchical linear and logistic regression models were created for the cost and complication outcomes. Random hospital intercepts were used to assess between-hospital variation. We evaluated the reliability of each measure by study year and examined the number of hospitals meeting different thresholds of reliability by year.

Results: We included a total of 66,571 elective lumbar fusion surgeries for spondylolisthesis performed at 244 hospitals during the study period. The mean 90-day hospital cost was $30,827 (2019 dollars). 12.0% of patients experienced a complication within 90 days of surgery, including 7.8% who had a serious complication. The median reliability of 90-day cost ranged from 0.97-0.99 across study years, and there was a narrow distribution of reliability values. By comparison, the median reliability for the overall complication metric ranged from 0.22 to 0.44, and the reliability of the serious complication measure ranged from 0.30 to 0.49 across the study years. At least 96% of hospitals had high (> 0.7) reliability for cost in any year, whereas only 0-9% and 0-11% of hospitals reached this cutoff for the overall and serious complication rate in any year, respectively. By comparison, 10-69% of hospitals per year achieved a more moderate threshold of 0.4 reliability for overall complications, compared to 21-80% of hospitals who achieved this lower reliability threshold for serious complications.

Conclusions: 90-day inpatient costs are highly reliable for assessing variation across hospitals, whereas overall and serious complications are only moderately reliable for profiling performance. These results support the viability of emerging bundled payment programs that assume true differences in costs of care exist across hospitals.
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http://dx.doi.org/10.1016/j.spinee.2021.06.014DOI Listing
June 2021

Defining a Surgical Invasiveness Threshold for Increased Risk of a Major Complication Following Adult Spinal Deformity Surgery.

Spine (Phila Pa 1976) 2021 Jul;46(14):931-938

Department of Orthopedic Surgery, The Johns Hopkins University, Baltimore, MD.

Study Design: Retrospective review.

Objectives: The aim of this study was to define a surgical invasiveness threshold that predicts major complications after adult spinal deformity (ASD) surgery; use this threshold to categorize patients into quartiles by invasiveness; and determine the odds of major complications by quartile.

Summary Of Background Data: Understanding the relationship between surgical invasiveness and major complications is important for estimating the likelihood of major complications after ASD surgery.

Methods: Using a multicenter database, we identified 574 ASD patients (more than 5 levels fused; mean age, 60 ± 15 years) with minimum 2-year follow-up. Invasiveness was calculated as the ASD Surgical and Radiographic (ASD-SR) score. Youden index was used to identify the invasiveness score cut-off associated with optimal sensitivity and specificity for predicting major complications. Resulting high- and low-invasiveness groups were divided in half to create quartiles. Odds of developing a major complication were analyzed for each quartile using logistic regression (alpha = 0.05).

Results: The ASD-SR cutoff score that maximally predicted major complications was 90 points. ASD-SR quartiles were 0 to 65 (Q1), 66 to 89 (Q2), 90 to 119 (Q3), and ≥120 (Q4). Risk of a major complication was 17% in Q1, 21% in Q2, 35% in Q3, and 33% in Q4 (P < 0.001). Comparisons of adjacent quartiles showed an increase in the odds of a major complication from Q2 to Q3 (odds ratio [OR] 1.8; 95% confidence interval [CI]: 1.0-3.0), but not from Q1 to Q2 or from Q3 to Q4. Patients with ASD-SR scores ≥90 were 1.9 times as likely to have a major complication than patients with scores <90 (OR 1.9, 95% CI 1.3-2.9). Mean ASD-SR scores above and below 90 points were 121 ± 25 and 63 ± 17, respectively.

Conclusion: The odds of major complications after ASD surgery are significantly greater when the procedure has an ASD-SR score ≥90. ASD-SR score can be used to counsel patients regarding these increased odds.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003949DOI Listing
July 2021

Effects of temperature on chaotropic anion-induced shape transitions of star molecular bottlebrushes with heterografted poly(ethylene oxide) and poly(,-dialkylaminoethyl methacrylate) side chains in acidic water.

Soft Matter 2021 Jul;17(27):6566-6579

Department of Chemistry, University of Tennessee, Knoxville, Tennessee 37996, USA.

This article reports a study of the effects of temperature on chaotropic anion (CA)-induced star-globule shape transitions in acidic water of three-arm star bottlebrushes composed of heterografted poly(ethylene oxide) (PEO) and either poly(2-(N,N-dimethylamino)ethyl methacrylate) (PDMAEMA) or poly(2-(N,N-diethylamino)ethyl methacrylate) (PDEAEMA) (the brushes denoted as SMB-11 and -22, respectively). The brush polymers were synthesized by grafting alkyne-end-functionalized PEO and PDMAEMA or PDEAEMA onto an azide-bearing three-arm star backbone polymer using the copper(i)-catalyzed alkyne-azide cycloaddition reaction. Six anions were studied for their effects on the conformations of SMB-11 and -22 in acidic water: super CAs [Fe(CN)6]3- and [Fe(CN)6]4-, moderate CAs PF6- and ClO4-, weak CA I-, and for comparison, kosmotropic anion SO42-. At 25 °C, the addition of super and moderate CAs induced shape transitions of SMB-11 and -22 in pH 4.50 water from a starlike to a collapsed globular state stabilized by PEO side chains, which was driven by the ion pairing of protonated tertiary amine groups with CAs and the chaotropic effect. The shape changes occurred at much lower salt concentrations for super CAs than moderate CAs. Upon heating from near room temperature to 70 °C, the super CA-collapsed brushes remained in the globular state, whereas the moderate CA-collapsed brushes underwent reversible globule-to-star shape transitions. The transition temperature increased with increasing salt concentration and was found to be higher for SMB-22 at the same salt concentration, presumably caused by the chaotropic effect. In contrast, I- and SO42- had small effects on the conformations of SMB-11 and -22 at 25 °C in the studied salt concentration range, and only small and gradual size variations were observed upon heating to 70 °C. The results reported here may have potential uses in the design of stimuli-responsive systems for substance encapsulation and release.
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http://dx.doi.org/10.1039/d1sm00728aDOI Listing
July 2021

Discovery of Arylsulfonamide Na1.7 Inhibitors: IVIVC, MPO Methods, and Optimization of Selectivity Profile.

ACS Med Chem Lett 2021 Jun 1;12(6):1038-1049. Epub 2021 Jun 1.

Discovery Chemistry, Merck & Co., Inc., West Point, Pennsylvania 19486, United States.

The voltage-gated sodium channel Na1.7 continues to be a high-profile target for the treatment of various pain afflictions due to its strong human genetic validation. While isoform selective molecules have been discovered and advanced into the clinic, to date, this target has yet to bear fruit in the form of marketed therapeutics for the treatment of pain. Lead optimization efforts over the past decade have focused on selectivity over Na1.5 due to its link to cardiac side effects as well as the translation of preclinical efficacy to man. Inhibition of Na1.6 was recently reported to yield potential respiratory side effects preclinically, and this finding necessitated a modified target selectivity profile. Herein, we report the continued optimization of a novel series of arylsulfonamide Na1.7 inhibitors to afford improved selectivity over Na1.6 while maintaining rodent oral bioavailability through the use of a novel multiparameter optimization (MPO) paradigm. We also report - correlations from Na1.7 electrophysiology protocols to preclinical models of efficacy to assist in projecting clinical doses. These efforts produced inhibitors such as compound with potency against Na1.7, selectivity over Na1.5 and Na1.6, and efficacy in behavioral models of pain in rodents as well as inhibition of rhesus olfactory response indicative of target modulation.
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http://dx.doi.org/10.1021/acsmedchemlett.1c00218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201757PMC
June 2021

What Is the Optimal Irrigation Solution in the Management of Periprosthetic Hip and Knee Joint Infections?

J Arthroplasty 2021 May 26. Epub 2021 May 26.

Department of Orthopedics, Rothman Orthopedics, Philadelphia, PA.

Background: Thorough irrigation and debridement using an irrigation solution is a well-established treatment for both acute and chronic periprosthetic joint infections (PJIs). In the absence of concrete data, identifying the optimal irrigation agent and protocol remains challenging.

Methods: A thorough review of the current literature on the various forms of irrigations and their additives was performed to evaluate the efficacy and limitations of each solution as pertaining to pathogen eradication in the treatment of PJI. As there is an overall paucity of high-quality literature comparing irrigation additives to each other and to any control, no meta-analyses could be performed. The literature was therefore summarized in this review article to give readers concise information on current irrigation options and their known risks and benefits.

Results: Antiseptic solutions include povidone-iodine, chlorhexidine gluconate, acetic acid, hydrogen peroxide, sodium hypochlorite, hypochlorous acid, and preformulated commercially available combination solutions. The current literature suggests that intraoperative use of antiseptic irrigants may play a role in treating PJI, but definitive clinical studies comparing antiseptic to no antiseptic irrigation are lacking. Furthermore, no clinical head-to-head comparisons of different antiseptic irrigants have identified an optimal irrigation solution.

Conclusion: Further high-quality studies on the optimal irrigation additive and protocol for the management of PJI are warranted to guide future evidence-based decisions.
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http://dx.doi.org/10.1016/j.arth.2021.05.032DOI Listing
May 2021

Colon capsule endoscopy is a viable alternative to colonoscopy for the investigation of intermediate- and low-risk patients with gastrointestinal symptoms: results of a pilot study.

Endosc Int Open 2021 Jun 27;9(6):E965-E970. Epub 2021 May 27.

Department of Gastroenterology, Tallaght University Hospital, Dublin, Ireland.

Colon capsule endoscopy (CCE) is a recommended viable alternative to colonoscopy for colonic visualisation in a variety of clinical settings with proven efficacy in polyp detection, surveillance, screening and Inflammatory Bowel Disease (IBD) assessment. CCE efficacy in an unselected average risk symptomatic cohort has yet to be established. The aim of this study was to determine the feasibility of CCE imaging assessment in average risk symptomatic patients as an alternative to colonoscopy with and without additional biomarker assessment. This was a prospective, single-center comparison study of colonoscopy, CCE and biomarker assessment. Of 77 invited subjects, 66 underwent both a CCE and colonoscopy. A fecal immunochemical test (FIT) and fecal calprotectin (FC) were available in 56 and 59 subjects. In all 64 % (n = 42) had any positive finding with 16 (24 %) found to have significant disease (high-risk adenomas, IBD) on colonoscopy. The CCE completion rate was 76 %, five (8 %) had an inadequate preparation, the CCE polyp detection rate was high at 35 %. The sensitivity, specificity, positive and negative predictive values of CCE for significant disease were 81 %, 98 %, 93 % and 94 % respectively. In addition, three (5 %) significant small bowel diagnoses were made on CCE. FC and FIT were frequently elevated in patients with both colitis (5/7, 71 %) and high-risk adenomas (4/7 57 %). While both had a low positive predictive value for clinically significant disease, FIT 32 % and FC 26 %. CCE is a safe and effective alternative to colonoscopy in symptomatic average risk patients with or without the addition of biomarker screening.
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http://dx.doi.org/10.1055/a-1401-9528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159609PMC
June 2021

Bedtime Oral Hygiene Behaviours, Dietary Habits and Children's Dental Health.

Children (Basel) 2021 May 19;8(5). Epub 2021 May 19.

Dental Health Unit, Division of Dentistry, The University of Manchester, Manchester M1 5GH, UK.

Oral hygiene behaviours as well as dietary habits before bed can affect children's dental health resulting in higher prevalence of dental disease. Dental disease can affect children's health, development and even school performance. If left untreated, dental disease can progress and it can lead to extractions under general anaesthetic causing further distress for children and families. Consistent and appropriate oral hygiene behaviours and dietary habits can prevent dental diseases from occurring in the first place. This cross-sectional study examines the relationship between oral hygiene behaviours, dietary habits around bedtime and children's dental health. A total of 185 parents with children between the ages of 3 and 7 years from deprived areas participated in the study. Data on bedtime routine activities were collected using an automated text-survey system. Children's dental health status was established through examination of dental charts and dmft (decayed, missed, filled teeth) scores. : In total, 52.4% of parents reported that their children's teeth were brushed every night. The majority of children (58.9%) had dmft scores over zero. In total, 51 (46.7% of children with dmft score over 0 and 27.5% of all children) children had active decay. The mean dmft score for those experiencing decay was 2.96 (SD = 2.22) with an overall mean dmft score of 1.75 (SD = 2.24). There were significant correlations between frequency of tooth brushing, frequency of snacks/drinks before bed and dmft scores (r = -0.584, < 0.001 and r = 0.547, = 0.001 respectively). Finally, higher brushing frequency was associated with a lower likelihood of a dmft score greater than 0 (Exp(B) = 0.9). Despite families implementing oral hygiene behaviours as part of their bedtime routines those behaviours varied in their consistency. Results of this study highlight the need for additional studies that consider bedtime routine-related activities and especially the combined effects of oral hygiene practices and dietary habits due to their potentially important relationship with children's dental health.
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http://dx.doi.org/10.3390/children8050416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160840PMC
May 2021

Definitive fixation outcomes of open tibial shaft fractures: Systematic review and network meta-analysis.

J Orthop Trauma 2021 Mar 27. Epub 2021 Mar 27.

Department of Orthopaedic Surgery, The Royal Infirmary of Edinburgh, Edinburgh, United Kingdom. Department of Orthopaedic Surgery, Southmead Hospital, Bristol, United Kingdom. Department of Orthopaedic Surgery, The Royal National Orthopaedic Hospital, Stanmore, United Kingdom. Department of Orthopaedic Surgery, McMaster University, Ontario, Canada Department of Orthopaedic Surgery, Boston Medical Center, Boston, USA.

Objectives: To delineate if there were differences in outcomes between definitive fixation strategies in open tibial shaft fractures.

Data Sources: MEDLINE, EMBASE, CENTRAL, OpenGrey.

Study Selection: Randomized and Quasi-randomized studies analyzing adult patients (>18 years) with open tibial shaft fractures (AO-42), undergoing definitive fixation treatment of any type.

Data Extraction: Data regarding patient demographics, definitive bony/soft-tissue management, irrigation, type of antibiotics and follow up. Definitive intervention choices included unreamed intramedullary nailing (UN), reamed intramedullary nailing (RN), plate fixation, multiplanar, and uniplanar external fixation (EF). The primary outcome was unplanned reoperation rate. Cochrane risk of bias tool and GRADE systems were used for quality analysis.

Data Synthesis: A random-effects meta-analysis of head-to-head evidence, followed by a network analysis that modelled direct and indirect data was conducted to provide precise estimates (relative risks (RR) and associated 95% confidence intervals (95% CI)).

Results: In open tibial shaft fractures, direct comparison UN showed a lower risk of unplanned reoperation versus EF (RR 0.67, 95% CI 0.43 - 1.05, p=0.08, moderate confidence). In Gustilo type III open fractures, the risk reduction with nailing compared to EF was larger (RR 0.61, 95% CI 0.37 - 1.01, p=0.05, moderate confidence). UN had a lower reoperation risk compared to RN (RR 0.91, 95% CI 0.58 - 1.4, p=0.68, low confidence), however this was not significant and did not demonstrate a clear advantage.

Conclusion: Intramedullary nailing reduces the risk of unplanned reoperation by a third compared to EF, with a slightly larger reduction in type III open fractures. Future trials should focus on major complication rates and health-related quality of life in high-grade tibial shaft fractures.

Level Of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.1097/BOT.0000000000002090DOI Listing
March 2021

Life-Threatening Intraparenchymal Hemorrhage of Steroid-Induced Hepatic Adenomas in a Healthy Man.

ACG Case Rep J 2021 May 24;8(5):e00601. Epub 2021 May 24.

Department of Surgery, Beacon Hospital, Sandyford, Dublin, Ireland.

Hepatocellular adenomas are uncommon benign epithelial tumors of the liver that are associated with several risk factors such as anabolic androgens and oral contraceptive pills. They may present as incidental findings, with abdominal pain or hemorrhage. This case report details the presentation and management of a life-threatening hepatocellular adenomas hemorrhage in a seemingly healthy 28-year-old man. After initial conservative management, a clinical deterioration prompted urgent reevaluation and successful embolization of the liver through transarterial embolization. As oral contraceptive pills use and anabolic steroid abuse have become more prevalent in recent decades, we may begin to see more of these presentations.
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http://dx.doi.org/10.14309/crj.0000000000000601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148419PMC
May 2021

The odontoid-CSVL distance in a global population of asymptomatic volunteers: normative values and implications for spinal coronal alignment.

Eur Spine J 2021 May 19. Epub 2021 May 19.

Department of Orthopedic Surgery, Columbia University Medical Center, The Och Spine Hospital at New York Presbyterian, New York, USA.

Purpose: In a population of asymptomatic volunteers across 5 countries, we sought to: (a) establish normative values of the Odontoid-Central Sacral Vertical Line (OD-CSVL) across patient factors, and (b) assess correlations of OD-CSVL with other radiographic parameters.

Methods: A prospective, cross-sectional study of asymptomatic adult volunteers, ages 18-80 years, were enrolled across 5 countries (France, Japan, Singapore, Tunisia, United States) forming the Multi-Ethnic Alignment Normative Study (MEANS) cohort. Included volunteers had no known spinal disorder(s), no significant neck/back pain (VAS ≤ 2; ODI ≤ 20), and no significant scoliosis (Cobb ≤ 20°). Radiographic measurements included commonly used coronal alignment parameters (mm) and angles (°). OD-CSVL was defined as the difference between the odontoid plumb line (line from the tip of the odontoid vertically down) and the CSVL (vertical line from the center of the sacrum). Chi-square, student's t tests, Kruskal-Wallis, Wilcoxon rank-sum, linear regression, and Pearson's correlation were used with significance at p < 0.05.

Results: 467 volunteers were included with normative OD-CSVL values by age decade, gender, BMI, and country. Mean ± SD OD-CSVL was 8.3 mm ± 6.5 mm and 31 (6.6%) volunteers were almost perfectly aligned (OD-CSVL < 1 mm). A linear relationship was seen between OD-CSVL with both age (p < 0.001) and BMI (p = 0.015). Significant variation was seen between OD-CSVL and 5 different ethnicities (p = 0.004). OD-CSVL correlated best with other coronal radiographic parameters, C7-CSVL (r = 0.743, p < 0.001), OD-knee (r = 0.230, p < 0.001), CAM-knee (r = 0.612, p < 0.001), and regional TL cobb angle (r = 0.4214, p = 0.005).

Conclusion: Among asymptomatic volunteers, increased OD-CSVL was significantly associated with increased age, increased BMI, and ethnicity, but not gender. OD-CSVL correlated strongest with C7-CSVL, TL cobb angle, OD-knee, and CAM-knee. OD-CSVL. These results support further study of OD-CSVL in symptomatic adult spine deformity patients.
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http://dx.doi.org/10.1007/s00586-021-06873-6DOI Listing
May 2021

Telephone Fracture Clinic Consultations: A Satisfactory Solution in Lockdown.

Cureus 2021 Apr 8;13(4):e14371. Epub 2021 Apr 8.

Trauma and Orthopaedics, Southmead Hospital, Bristol, GBR.

Introduction The COVID-19 pandemic was a catalyst to many learning opportunities within clinical practice in the UK. Attempts were made to reduce footfall within all institutions and within the study unit; this led to alterations in fracture clinic provision. An alternative method was developed whereby most of the initial contacts were in person and much of the follow-up was done remotely. The aim of this study was to evaluate patient satisfaction and views on this alteration in service. Methods The first 299 patients who had fracture clinic appointments delivered by telephone consultation at this institution during the pandemic in early 2020 were retrospectively identified and sent a postal survey. Satisfaction levels were assessed through a degree of agreement with statements (nine items), yes/no answers (four questions), and space for comments. Results One hundred and thirty-one survey responses were included (44% response rate). The majority of patients (82%) were satisfied overall with the care they received. Although 78% of patients stated that they preferred a telephone consultation to attend a face-to-face hospital appointment during the pandemic, only 22% stated they would have preferred this in normal (pre-COVID-19) times. Interestingly 62% of patients stated they would be happy for further fracture clinic appointments to be carried out in the same way. Discussion Most of the remote consultations were in follow-up rather than new patients. Patients were adaptable to this alternative method of care delivery. There could be a role for its integration into the options for fracture clinic delivery in the future.
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http://dx.doi.org/10.7759/cureus.14371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106481PMC
April 2021

Translating Data Analytics Into Improved Spine Surgery Outcomes: A Roadmap for Biomedical Informatics Research in 2021.

Global Spine J 2021 May 11:21925682211008424. Epub 2021 May 11.

Department of Neurological Surgery, 12275Washington University School of Medicine, St. Louis, MO, USA.

Study Design: Narrative review.

Objectives: There is growing interest in the use of biomedical informatics and data analytics tools in spine surgery. Yet despite the rapid growth in research on these topics, few analytic tools have been implemented in routine spine practice. The purpose of this review is to provide a health information technology (HIT) roadmap to help translate data assets and analytics tools into measurable advances in spine surgical care.

Methods: We conducted a narrative review of PubMed and Google Scholar to identify publications discussing data assets, analytical approaches, and implementation strategies relevant to spine surgery practice.

Results: A variety of data assets are available for spine research, ranging from commonly used datasets, such as administrative billing data, to emerging resources, such as mobile health and biobanks. Both regression and machine learning techniques are valuable for analyzing these assets, and researchers should recognize the particular strengths and weaknesses of each approach. Few studies have focused on the implementation of HIT, and a variety of methods exist to help translate analytic tools into clinically useful interventions. Finally, a number of HIT-related challenges must be recognized and addressed, including stakeholder acceptance, regulatory oversight, and ethical considerations.

Conclusions: Biomedical informatics has the potential to support the development of new HIT that can improve spine surgery quality and outcomes. By understanding the development life-cycle that includes identifying an appropriate data asset, selecting an analytic approach, and leveraging an effective implementation strategy, spine researchers can translate this potential into measurable advances in patient care.
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http://dx.doi.org/10.1177/21925682211008424DOI Listing
May 2021

Postoperative Rehabilitation of Chronic Lateral Ankle Instability: A Systematic Review.

Sports Med Arthrosc Rev 2021 Jun;29(2):146-152

Orthopaedics and Medstar Orthopaedic Institute, Medstar Georgetown Universitiy Hospital, DC.

Chronic lateral ankle instability often causes adults to require a surgical intervention with subsequent physical therapy to assist with returning to their prior level of function. This systematic review is hoping to provide an up to date understanding of surgical procedures performed to correct chronic lateral ankle instability and establish a protocol for others to follow when treating adults who are status-post chronic lateral ankle instability surgery. This review looked at level I to III research studies that included surgical interventions to correct chronic lateral ankle instability as well as a rehabilitation protocol. This study found implementation of a rehabilitation protocol after surgical intervention could improve balance and subjective functional outcomes. It also determined that early weight-bearing may allow for early strengthening as range of motion returns faster. Further research is required utilizing larger randomized studies to better evaluate the outcomes of specific rehabilitation protocols in this patient population.
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http://dx.doi.org/10.1097/JSA.0000000000000304DOI Listing
June 2021

Predictors of serious, preventable, and costly medical complications in a population of adult spinal deformity patients.

Spine J 2021 May 8. Epub 2021 May 8.

Department of Orthopaedic Surgery, University of California Davis, Davis, CA, USA.

Background Context: In 2008, the Centers for Medicare and Medicaid Services (CMS) established a list of hospital-acquired conditions (HACs) with significant deleterious effects on both patients and providers. Adult spinal deformity (ASD) surgery is complex and highly invasive, and as such may result in significant morbidity including these HACs.

Purpose: Identify predictors for developing the most common HACs among adult spinal deformity (ASD) patients undergoing corrective surgery.

Study Design/setting: Retrospective analysis.

Patient Sample: One thousand one hundred and seventy-one ASD patients.

Outcome Measures: HACs, Health-Related Quality of Life scores(HRQLs), Reoperation, Integrated Health State (IHS) METHODS: ASD pts undergoing surgery (>18 years, scoliosis ≥20°, SVA ≥5 cm, PT ≥25° and/or TK >60°) with complete data at BL and up to 2 years post-op were included. Patients were stratified by presence of >1 HAC, defined as at least one superficial/deep SSI, UTI, DVT, or PE within a 30-day post-op window. Random forest analysis generated 5,000 Conditional Inference Trees to compute a variable importance table for top predictors of HACs. An area-under-the-curve (AUC) methodology compared normalized HRQL scores between groups to determine an IHS with 2-year follow-up.

Results: Total of 1,171 pts (59.8 years, 76.2%F, 28.1kg/m) underwent corrective ASD surgery, with 1,053 pts in the non-HAC group and 118 in the HAC group. Of these pts, 25.4% had UTI, 15.4% DVT, 19.2% superficial SSI, 20.8% deep SSI, and 19.2% PE. HAC pts were on average older (63.5 vs 59.3, p=.004) and more often frail (51.3 vs 39.7%, p=.021) than non-HAC pts. Postop LOS and reoperation were most associated with HAC groups: [1] LOS >7 days [2] reoperation. Patient-related predictors of HACs were [3] age >50 yerr, [4] frailty, and [13] BMI >31. Procedure-related predictors of HACs were [5] operative-time >405 minutes, [6] levels fused >9, EBL >1450 mL, and [11] decompression. BL radiographic predictors were [7] PT >20°, [9] PI-LL>6°, [10] TL Cobb angle >15°, [12] SVA C7-S1 >29 mm. No differences were observed between groups with regards to IHS ODI (0.73 vs 0.74, p=.863), SRS (1.3 vs1.3, p=.374), NRS Back (0.6 vs 0.6, p=.158). HAC had higher rates of reoperation than non-HAC (0.08 vs 0.01, p=.066), and any HAC within 30-days of index was a significant predictor of reoperation (OR: 2.448 [1.94-3.09], p<.001).

Conclusions: In a population of ASD patients, HACs were associated with length of stay, reoperation, age, and frailty. Radiographic parameters such as pelvic tilt >20°, PI-LL >6°, & SVA >29 mm also increased odds of HACs, and should raise postoperative awareness for HAC development.
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http://dx.doi.org/10.1016/j.spinee.2021.04.020DOI Listing
May 2021

Obese societies: Reconceptualising the challenge for public health.

Sociol Health Illn 2021 May 8;43(4):1051-1067. Epub 2021 May 8.

Department of Public Health and Primary Care, Cambridge University, Cambridge, UK.

The prevalence of obesity and related health problems has increased sharply in recent decades. Dominant medical, economic, psychological, and especially epidemiological accounts conceptualise these trends as outcomes of individuals' lifestyles - whether freely chosen or determined by an array of obesogenic factors. As such, they rest on forms of methodological individualism, causal narratives, and a logic of substitution in which people are encouraged to set currently unhealthy ways of life aside. This article takes a different approach, viewing trends in obesity as consequences of the dynamic organisation of social practices across space and time. By combining theories of practice with emerging accounts of epigenetics, we explain how changing constellations of practices leave their marks on the body. We extend the concept of biohabitus to show how differences in health, well-being, and body shape are passed on as relations between practices are reproduced and transformed over time. In the final section, we take stock of the practical implications of these ideas and conclude by making the case for extended forms of enquiry and policy intervention that put the organisation of practices front and centre.
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http://dx.doi.org/10.1111/1467-9566.13275DOI Listing
May 2021

Operative versus nonoperative treatment for adult symptomatic lumbar scoliosis at 5-year follow-up: durability of outcomes and impact of treatment-related serious adverse events.

J Neurosurg Spine 2021 Apr 30:1-13. Epub 2021 Apr 30.

2Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, Missouri.

Objective: Although short-term adult symptomatic lumbar scoliosis (ASLS) studies favor operative over nonoperative treatment, longer outcomes are critical for assessment of treatment durability, especially for operative treatment, because the majority of implant failures and nonunions present between 2 and 5 years after surgery. The objectives of this study were to assess the durability of treatment outcomes for operative versus nonoperative treatment of ASLS, to report the rates and types of associated serious adverse events (SAEs), and to determine the potential impact of treatment-related SAEs on outcomes.

Methods: The ASLS-1 (Adult Symptomatic Lumbar Scoliosis-1) trial is an NIH-sponsored multicenter prospective study to assess operative versus nonoperative ASLS treatment. Patients were 40-80 years of age and had ASLS (Cobb angle ≥ 30° and Oswestry Disability Index [ODI] ≥ 20 or Scoliosis Research Society [SRS]-22 subscore ≤ 4.0 in the Pain, Function, and/or Self-Image domains). Patients receiving operative and nonoperative treatment were compared using as-treated analysis, and the impact of related SAEs was assessed. Primary outcome measures were ODI and SRS-22.

Results: The 286 patients with ASLS (107 with nonoperative treatment, 179 with operative treatment) had 2-year and 5-year follow-up rates of 90% (n = 256) and 74% (n = 211), respectively. At 5 years, compared with patients treated nonoperatively, those who underwent surgery had greater improvement in ODI (mean difference -15.2 [95% CI -18.7 to -11.7]) and SRS-22 subscore (mean difference 0.63 [95% CI 0.48-0.78]) (p < 0.001), with treatment effects (TEs) exceeding the minimum detectable measurement difference (MDMD) for ODI (7) and SRS-22 subscore (0.4). TEs at 5 years remained as favorable as 2-year TEs (ODI -13.9, SRS-22 0.52). For patients in the operative group, the incidence rates of treatment-related SAEs during the first 2 years and 2-5 years after surgery were 22.38 and 8.17 per 100 person-years, respectively. At 5 years, patients in the operative group who had 1 treatment-related SAE still had significantly greater improvement, with TEs (ODI -12.2, SRS-22 0.53; p < 0.001) exceeding the MDMD. Twelve patients who received surgery and who had 2 or more treatment-related SAEs had greater improvement than nonsurgically treated patients based on ODI (TE -8.34, p = 0.017) and SRS-22 (TE 0.32, p = 0.029), but the SRS-22 TE did not exceed the MDMD.

Conclusions: The significantly greater improvement of operative versus nonoperative treatment for ASLS at 2 years was durably maintained at the 5-year follow-up. Patients in the operative cohort with a treatment-related SAE still had greater improvement than patients in the nonoperative cohort. These findings have important implications for patient counseling and future cost-effectiveness assessments.
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http://dx.doi.org/10.3171/2020.9.SPINE201472DOI Listing
April 2021

The role of intraoperative radiotherapy in advanced rectal cancer: a meta-analysis.

Colorectal Dis 2021 Apr 27. Epub 2021 Apr 27.

University College Dublin, Belfield, Dublin 4, Ireland.

Aim: Patients with locally advanced and locally recurrent rectal cancer (LARC/LRRC) experience higher rates of local recurrence (LR) and poorer overall survival than patients with primary rectal cancer restricted to the mesorectum despite improved neoadjuvant treatment regimens and radical surgical procedures. Intraoperative radiotherapy (IORT) has been suggested as an adjunctive tool in the surgical management of these challenging cases. However, clear evidence regarding the oncological benefit of IORT is sparse. The aim of this review was to update this evidence in the era of standardized neoadjuvant radiotherapy administration.

Method: A systematic review of patients who received IORT as part of multimodal treatment for advanced rectal cancer from 2000 to 2020 and an analysis of IORT and surgery/external beam radiotherapy (EBRT) groups was performed. The primary endpoint was the rate of LR between the two groups.

Results: Seven papers met the predefined criteria. LR was reduced by the addition of IORT when compared with the surgery/EBRT alone group (14.7% vs. 21.4%; OR 0.55, 95% CI 0.27-1.14; p = 0.11). There was no increase in reported genitourinary morbidity, wound issues, pelvic collections or anastomotic leak in those patients who received IORT. Notably, there was no survival difference between the two groups.

Conclusion: The addition of IORT to current treatment strategies in the management of patients with LARC/LRRC is associated with a lower rate of locoregional recurrence without increased morbidity. However, this marks a highly selective group of patients, with heterogeneity regarding indications, prior neoadjuvant treatments and/or IORT dosing.
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http://dx.doi.org/10.1111/codi.15698DOI Listing
April 2021

Short-term outcomes in older patients with peritoneal malignancy treated with cytoreductive surgery and HIPEC: Experience with 245 patients from a national centre.

Eur J Surg Oncol 2021 Apr 14. Epub 2021 Apr 14.

National Centre for Peritoneal Malignancy, Department of Surgery, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.

Background: Cytoreductive Surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly accepted as the optimal management of selected patients with peritoneal malignancy. There is limited published evidence on outcomes in older patients treated by this complex therapeutic strategy.

Methods: A retrospective review of a prospective database of all patients who underwent CRS with HIPEC in a single institution over seven years. A comparative analysis of outcomes in patients under 65 undergoing CRS and HIPEC with patients ≥65 years was performed. The key endpoints were morbidity, mortality, reintervention rate and length of stay in the high dependency/intensive care (HDU/ICU) units.

Results: Overall, 245 patients underwent CRS and HIPEC during the study period, with 76/245 (31%) ≥65 years at the time of intervention. Tumour burden measured by the peritoneal carcinomatosis index (PCI) score was a median of 11 for both groups. Median length of hospital stay in the ≥65-year-old group was 14.5 days versus 13 days in the <65-year-old group (∗p = 0.01). Patients aged ≥65-years spent a median of one more day in the critical care unit ∗(p = 0.001). Significant morbidity (Clavien-Dindo ≥ Grade IIIa) was higher in the ≥65-year than the <65-year group (18.4% versus 11.2%). There were no perioperative deaths in the ≥65-year group.

Conclusion: This study demonstrates higher perioperative major morbidity in ≥65-year group, but with low mortality in patients undergoing CRS/HIPEC for disseminated intraperitoneal malignancy. This increased morbidity does not translate into higher rates of re-interventions and highlights the importance of optimal patient selection.
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http://dx.doi.org/10.1016/j.ejso.2021.04.004DOI Listing
April 2021

Mapping sub-cellular protein aggregates and lipid inclusions using synchrotron ATR-FTIR microspectroscopy.

Analyst 2021 Jun 21;146(11):3516-3525. Epub 2021 Apr 21.

School of Molecular and Life Sciences, Curtin University, Bentley, 6845, Western Australia. and Curtin Health Innovation Research Institute, Curtin University, Bentley, 6102, Western Australia.

Visualising direct biochemical markers of cell physiology and disease pathology at the sub-cellular level is an ongoing challenge in the biological sciences. A suite of microscopies exists to either visualise sub-cellular architecture or to indirectly view biochemical markers (e.g. histochemistry), but further technique developments and innovations are required to increase the range of biochemical parameters that can be imaged directly, in situ, within cells and tissue. Here, we report our continued advancements in the application of synchrotron radiation attenuated total reflectance Fourier transform infrared (SR-ATR-FTIR) microspectroscopy to study sub-cellular biochemistry. Our recent applications demonstrate the much needed capability to map or image directly sub-cellular protein aggregates within degenerating neurons as well as lipid inclusions within bacterial cells. We also characterise the effect of spectral acquisition parameters on speed of data collection and the associated trade-offs between a realistic experimental time frame and spectral/image quality. Specifically, the study highlights that the choice of 8 cm spectral resolutions provide a suitable trade-off between spectral quality and collection time, enabling identification of important spectroscopic markers, while increasing image acquisition by ∼30% (relative to 4 cm spectral resolution). Further, this study explores coupling a focal plane array detector with SR-ATR-FTIR, revealing a modest time improvement in image acquisition time (factor of 2.8). Such information continues to lay the foundation for these spectroscopic methods to be readily available for, and adopted by, the biological science community to facilitate new interdisciplinary endeavours to unravel complex biochemical questions and expand emerging areas of study.
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http://dx.doi.org/10.1039/d1an00136aDOI Listing
June 2021

ANCA-associated renal vasculitis is associated with rurality but not seasonality or deprivation in a complete national cohort study.

RMD Open 2021 04;7(2)

Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, UK.

Background: Small studies suggest an association between ANCA-associated vasculitis (AAV) incidence and rurality, seasonality and socioeconomic deprivation. We examined the incidence of kidney biopsy-proven AAV and its relationship with these factors in the adult Scottish population.

Methods: Using the Scottish Renal Biopsy Registry, all adult native kidney biopsies performed between 2014 and 2018 with a diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) were identified. The Scottish Government Urban Rural Classification was used for rurality analysis. Seasons were defined as autumn (September-November), winter (December-February), spring (March-May) and summer (June-August). Patients were separated into quintiles of socioeconomic deprivation using the validated Scottish Index of Multiple Deprivation and incidence standardised to age. Estimated glomerular filtration rate and urine protein:creatinine ratio at time of biopsy were used to assess disease severity.

Results: 339 cases of renal AAV were identified, of which 62% had MPA and 38% had GPA diagnosis. AAV incidence was 15.1 per million population per year (pmp/year). Mean age was 66 years and 54% were female. Incidence of GPA (but not MPA) was positively associated with rurality (5.2, 8.4 and 9.1 pmp/year in 'urban', 'accessible remote' and 'rural remote' areas, respectively; p=0.04). The age-standardised incidence ratio was similar across all quintiles of deprivation (p=ns).

Conclusions: Seasonality and disease severity did not vary across AAV study groups. In this complete national cohort study, we observed a positive association between kidney biopsy-proven GPA and rurality.
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http://dx.doi.org/10.1136/rmdopen-2020-001555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057563PMC
April 2021

Artificial intelligence clustering of adult spinal deformity sagittal plane morphology predicts surgical characteristics, alignment, and outcomes.

Eur Spine J 2021 Apr 15. Epub 2021 Apr 15.

Department of Orthopaedic Surgery, Warren Alpert Medical School of Brown University, Alpert Medical School, Providence, Rhode Island, 1 Kettle Point Avenue, East Providence, RI, 02914, USA.

Purpose: AI algorithms have shown promise in medical image analysis. Previous studies of ASD clusters have analyzed alignment metrics-this study sought to complement these efforts by analyzing images of sagittal anatomical spinopelvic landmarks. We hypothesized that an AI algorithm would cluster preoperative lateral radiographs into groups with distinct morphology.

Methods: This was a retrospective review of a multicenter, prospectively collected database of adult spinal deformity. A total of 915 patients with adult spinal deformity and preoperative lateral radiographs were included. A 2 × 3, self-organizing map-a form of artificial neural network frequently employed in unsupervised classification tasks-was developed. The mean spine shape was plotted for each of the six clusters. Alignment, surgical characteristics, and outcomes were compared.

Results: Qualitatively, clusters C and D exhibited only mild sagittal plane deformity. Clusters B, E, and F, however, exhibited marked positive sagittal balance and loss of lumbar lordosis. Cluster A had mixed characteristics, likely representing compensated deformity. Patients in clusters B, E, and F disproportionately underwent 3-CO. PJK and PJF were particularly prevalent among clusters A and E. Among clusters B and F, patients who experienced PJK had significantly greater positive sagittal balance than those who did not.

Conclusions: This study clustered preoperative lateral radiographs of ASD patients into groups with highly distinct overall spinal morphology and association with sagittal alignment parameters, baseline HRQOL, and surgical characteristics. The relationship between SVA and PJK differed by cluster. This study represents significant progress toward incorporation of computer vision into clinically relevant classification systems in adult spinal deformity.

Level Of Evidence Iv: Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.
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http://dx.doi.org/10.1007/s00586-021-06799-zDOI Listing
April 2021

Home blood pressure monitoring to improve hypertension control: a narrative review of international guideline recommendations.

Blood Press 2021 Apr 14:1-10. Epub 2021 Apr 14.

Department of Pharmacy Practice, Chapman University School of Pharmacy, Irvine, CA, USA.

Home blood pressure monitoring (HBPM) is a convenient way to assess out-of-office blood pressure control and is recommended by numerous international guidelines to aid clinicians in the diagnosis and management of essential hypertension. Although available guidelines recommend the use of HBPM in patients receiving antihypertensive medication, their specific recommendations regarding optimal monitoring schedule, duration, and clinician interpretation of home blood pressure readings may differ among guidelines. : The purpose of this article is to review available international hypertension guideline recommendations related to the use of HBPM to improve hypertension control among patients receiving antihypertensive therapy. We also briefly highlight clinical trials that have shown improved blood pressure control using HBPM to intensify antihypertensive therapy and provide a practical guide for implementing HBPM to improve hypertension control. Eleven international guidelines were identified and reviewed. In total, recommendations relating to which HBPM to use, number of measurements per day, and how to interpret home blood pressure values were largely in agreement among available guidelines. Clinicians recommending HBPM to their patients with hypertension should utilise a standardised HBPM protocol, based on available guideline recommendations.
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http://dx.doi.org/10.1080/08037051.2021.1911622DOI Listing
April 2021

Outcomes following synchronous liver resection, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal liver and peritoneal metastases: A bi-institutional study.

Surg Oncol 2021 Jun 2;37:101553. Epub 2021 Apr 2.

Peter MacCallum Cancer Centre, Department of Surgical Oncology, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia.

Purpose: Synchronous liver resection, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal liver (CRLM) and peritoneal metastases (CRPM) has traditionally been contraindicated. However, latest practice promotes specialist, multidisciplinary-led consideration for select patients. This study aimed to evaluate the perioperative and oncological outcomes of synchronous resection in the management of CRLM and CRPM from two tertiary referral centres.

Method: This bi-institutional, retrospective, cohort study included patients undergoing simultaneous liver resection, CRS and HIPEC for metastatic colorectal cancer from 2013 to 2020. Patients treated with ablative liver techniques, staged operative approaches and extra abdominal disease were excluded. Overall survival (OS) and disease-free survival (DFS) rates were assessed. Univariate and multivariate analyses identified variables associated with survival and major morbidity (Clavien-Dindo grade III/IV).

Results: Twenty-three patients were included. The median peritoneal carcinomatosis index (PCI) was 9 (range 0-22). There were two major liver resections and 21 minor resections. CC-0 resections were achieved in all patients. Major morbidity occurred in 7 patients. There were no deaths at 90 days. PCI was independently associated with morbidity (p = 0.04). PCI >10 (p = 0.069), major morbidity (p = 0.083) and presence of KRAS mutation (p = 0.052) approached significance for poor OS. Median follow up was 21 months (4-54 months). Median OS was 37 months, 3-year survival 54%, and median DFS 18 months.

Conclusion: Synchronous liver resection, cytoreductive surgery and HIPEC is feasible in selected patients with low-volume CRPM and CRLM. Increasing PCI is associated with postoperative major morbidity, and should be considered during operative planning.
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http://dx.doi.org/10.1016/j.suronc.2021.101553DOI Listing
June 2021
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