Publications by authors named "Richard Jones"

1,385 Publications

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Heart Rate as a Marker of Relapse During Withdrawal of Therapy in Recovered Dilated Cardiomyopathy.

JACC Heart Fail 2021 Jun 3. Epub 2021 Jun 3.

Cardiovascular Research Centre, Royal Brompton Hospital and National Heart Lung Institute, Imperial College, London, United Kingdom. Electronic address:

Objectives: The objective of this study was to determine the relationship between heart rate and relapse among patients in the TRED-HF (Therapy withdrawal in REcovered Dilated cardiomyopathy trial).

Background: Understanding markers and mechanisms of relapse among patients with recovered dilated cardiomyopathy (DCM) may enable personalized management.

Methods: The relationship between serial heart rate measurements and relapse was examined among patients in the TRED-HF trial, a randomized trial which examined the safety and feasibility of withdrawing heart failure therapy from 51 patients with recovered DCM over 6 months. In total, 25 patients were randomized to therapy withdrawal and 26 to continue therapy, of whom 25 subsequently began therapy withdrawal in a single arm crossover phase.

Results: The mean ± SD heart rate for those who had therapy withdrawn and did not relapse was 64.6 ± 10.7 beats/min at baseline and 74.7 ± 10.4 beats/min at follow-up, compared to 68.3 ± 11.3 beats/min at baseline and 86.1 ± 11.8 beats/min at follow-up for those who relapsed. After adjusting for differences in heart rate at baseline, patients who had therapy withdrawn and relapsed had a 10.4 beats/min (95% CI: 4.0-16.8) greater rise in heart rate than patients who had therapy withdrawn and did not relapse (P = 0.002). After data were adjusted for age, log N-terminal pro-B-type natriuretic peptide, and left ventricular ejection fraction (LVEF), heart rate (per 10 beats/min; hazard ratio [HR]: 1.65; 95% CI: 1.10 to 2.57; P = 0.01) and change in heart rate from baseline (per 10 beats/min; HR: 1.70; 95% CI: 1.12-2.57; p = 0.01) were associated with relapse. The results remained qualitatively the same after adjusting for beta-blocker dose.

Conclusions: For patients with DCM and improved LVEF, the rise in heart rate after treatment is withdrawn treatment identifies patients who are more likely to relapse. Whether the increase in heart rate is a marker or a mediator of relapse requires investigation. (Therapy withdrawal in REcovered Dilated cardiomyopathy trial [TRED]; NCT02859311).
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http://dx.doi.org/10.1016/j.jchf.2021.03.010DOI Listing
June 2021

A new integrated behavioural intervention for knee osteoarthritis: development and pilot study.

BMC Musculoskelet Disord 2021 Jun 8;22(1):526. Epub 2021 Jun 8.

Faculty of Health and Applied Sciences, University of the West of England, Bristol, BS16 1DD, UK.

Background: Exercise-based approaches have been a cornerstone of physiotherapy management of knee osteoarthritis for many years. However, clinical effects are considered small to modest and the need for continued adherence identified as a barrier to clinical efficacy. While exercise-based approaches focus on muscle strengthening, biomechanical research has identified that people with knee osteoarthritis over activate their muscles during functional tasks. Therefore, we aimed to create a new behavioural intervention, which integrated psychologically informed practice with biofeedback training to reduce muscle overactivity, and which was suitable for delivery by a physiotherapist.

Methods: Through literature review, we created a framework linking theory from pain science with emerging biomechanical concepts related to overactivity of the knee muscles. Using recognised behaviour change theory, we then mapped a set of intervention components which were iteratively developed through ongoing testing and consultation with patients and physiotherapists.

Results: The underlying framework incorporated ideas related to central sensitisation, motor responses to pain and also focused on the idea that increased knee muscle overactivity could result from postural compensation. Building on these ideas, we created an intervention with five components: making sense of pain, general relaxation, postural deconstruction, responding differently to pain and functional muscle retraining. The intervention incorporated a range of animated instructional videos to communicate concepts related to pain and biomechanical theory and also used EMG biofeedback to facilitate visualization of muscle patterns. User feedback was positive with patients describing the intervention as enabling them to "create a new normal" and to be "in control of their own treatment." Furthermore, large reductions in pain were observed from 11 patients who received a prototype version of the intervention.

Conclusion: We have created a new intervention for knee osteoarthritis, designed to empower individuals with capability and motivation to change muscle activation patterns and beliefs associated with pain. We refer to this intervention as Cognitive Muscular Therapy. Preliminary feedback and clinical indications are positive, motivating future large-scale trials to understand potential efficacy. It is possible that this new approach could bring about improvements in the pain associated with knee osteoarthritis without the need for continued adherence to muscle strengthening programmes.

Trial Registration: ISRCTN51913166 (Registered 24-02-2020, Retrospectively registered).
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http://dx.doi.org/10.1186/s12891-021-04389-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188786PMC
June 2021

Development and internal validation of a predictive model of cognitive decline 36 months following elective surgery.

Alzheimers Dement (Amst) 2021 21;13(1):e12201. Epub 2021 May 21.

Biogen Inc Cambridge Massachusetts USA.

Introduction: Our goal was to determine if features of surgical patients, easily obtained from the medical chart or brief interview, could be used to predict those likely to experience more rapid cognitive decline following surgery.

Methods: We analyzed data from an observational study of 560 older adults (≥70 years) without dementia undergoing major elective non-cardiac surgery. Cognitive decline was measured using change in a global composite over 2 to 36 months following surgery. Predictive features were identified as variables readily obtained from chart review or a brief patient assessment. We developed predictive models for cognitive decline (slope) and predicting dichotomized cognitive decline at a clinically determined cut.

Results: In a hold-out testing set, the regularized regression predictive model achieved a root mean squared error (RMSE) of 0.146 and a model r-square ( ) of .31. Prediction of "rapid" decliners as a group achieved an area under the curve (AUC) of .75.

Conclusion: Some of our models could predict persons with increased risk for accelerated cognitive decline with greater accuracy than relying upon chance, and this result might be useful for stratification of surgical patients for inclusion in future clinical trials.
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http://dx.doi.org/10.1002/dad2.12201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140204PMC
May 2021

Gender-related differences in the outcomes and genomic landscape of patients with myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes.

Br J Haematol 2021 Jun 24;193(6):1142-1150. Epub 2021 May 24.

Division of Hematological Malignancies and Bone Marrow Transplantation, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.

Myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes show a male predominance and men with MDS/MPN have worse outcomes, but it is unknown if the mutational burden differs between genders. We reviewed 167 patients with MDS/MPN and found that men had worse overall survival [hazard ratio (HR) 2·09, 95% confidence interval (CI) 1·16-3·75; P = 0·013] independent of subtype, Revised International Prognostic Scoring System score and age at diagnosis. We analysed the genomic data of a subset of 100 patients. Men had 0·88 more somatic mutations on average (95% CI 0·20-1·56, P = 0·011) independent of subtype, sample source and blast percentage. More somatic mutations was associated with a higher incidence of transformation to acute myeloid leukaemia (subdistribution HR 1·30, 95% CI 1·01-1·70; P = 0·046). Men had 0·70 more mutations in high-risk genes [additional sex combs like-1 (ASXL1), enhancer of zeste homolog 2 (EZH2), Runt-related transcription factor 1 (RUNX1), SET binding protein 1 (SETBP1), NRAS proto-oncogene, GTPase (NRAS), stromal antigen 2 (STAG2)] on average (95% CI 0·11-1·29, P = 0·021), and 13-times higher odds of harbouring an EZH2 mutation (95% CI 1·64-102·94, P = 0·015). The presence of an EZH2 mutation was associated with worse survival among men (HR 2·98, 95% CI 1·1-8·0; P = 0·031). Our present findings suggest that the worse outcomes in men with MDS/MPN are associated with a higher number of somatic mutations, especially in high-risk genes. These results warrant validation in larger cohorts and investigation of the underlying mechanisms.
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http://dx.doi.org/10.1111/bjh.17534DOI Listing
June 2021

Survival after autologous versus allogeneic transplantation in patients with relapsed and refractory Hodgkin lymphoma.

Leuk Lymphoma 2021 May 14:1-8. Epub 2021 May 14.

Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

For relapsed Hodgkin lymphoma, salvage chemotherapy followed by auto-HCT is the standard of care. It is important to identify subpopulations who could benefit from allo-HCT. This retrospective analysis included 277 patients with rrHL who underwent first transplant with auto-HCT or allo-HCT between 2007-2017. Patients in the auto-HCT cohort ( = 218) were older, more likely to be in CR at the time of transplant and receive maintenance therapy post-transplant. Patients who underwent allo-HCT ( = 59) had a higher MSKCC relapse score. Factors associated with an inferior PFS and OS included early relapse, advanced stage, extranodal involvement and not achieving CR following salvage chemotherapy. After controlling for these 4 risk factors and MSKCC score, PFS ( = 0.112) or OS ( = 0.256) was not affected by the choice of transplant. In patients with ≥ 3 high risk features, the 4-year PFS was 51% in the allo-HCT vs. 39% ( = 0.107) in the auto-HCT cohort.
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http://dx.doi.org/10.1080/10428194.2021.1927016DOI Listing
May 2021

Moderators of Age of Diagnosis in > 20,000 Females with Autism in Two Large US Studies.

J Autism Dev Disord 2021 May 7. Epub 2021 May 7.

Developmental Disorders Genetics Research Program, Emma Pendleton Bradley Hospital, East Providence, RI, USA.

The objective of this study was to determine the clinical features that moderate a later age at ASD diagnosis in females in a large sample of females with ASD. Within two large and independent ASD datasets (> 20,000 females), females were first diagnosed with ASD 14-months later relative to males. This later age at diagnosis was moderated by a mild or atypical presentation, wherein repetitive behaviors were limited, IQ and language were broadly intact, and recognized symptoms emerged later in development. Females are at risk for a later age at ASD diagnosis and treatment implementation, and modification of early childhood ASD screening methods for females may be warranted.
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http://dx.doi.org/10.1007/s10803-021-05026-4DOI Listing
May 2021

The effect of speed on Achilles tendon forces and patellofemoral joint stresses in high-performing endurance runners.

Scand J Med Sci Sports 2021 Apr 16. Epub 2021 Apr 16.

Human Movement and Rehabilitation, School of Health and Society, University of Salford, Salford, UK.

Achilles tendinopathy and patellofemoral pain are common running injuries associated with increased Achilles tendon (AT) forces and patellofemoral joint (PFJ) stresses. This study examined AT forces and PFJ stresses at different running speeds in high-performing endurance runners. Twenty runners ran overground at four running speeds (3.3, 3.9, 4.8, and 5.6 m/s). AT forces and PFJ stresses were estimated from kinematic and kinetic data. Repeated measures ANOVA with partial eta squared effect sizes was conducted to assess differences between running speeds. Increased peak AT forces (19.5%; p < 0.001) and loading rates (57.3%; p < 0.001) from 3.3 m/s to 5.6 m/s were observed. Cumulative AT loading was greater in the faster speeds compared to the slower speeds. Faster running speeds resulted in increased peak plantar flexor moments, increased peak plantar flexion angles, and a more flexed knee and an anterior center of pressure position at touchdown. Peak PFJ stress was lower in the slowest speed (3.3 m/s) compared to the faster running speeds (3.9-5.6 m/s; p = 0.005). PFJ stress loading rate significantly increased (43.6%; p < 0.001). Greater AT loading observed could be associated with strategies such as increased plantar flexor moments and altered lower body position at touchdown which are commonly employed to generate greater ground contact forces. Greater AT and PFJ loading rates were likely due to shorter ground contact times and therefore less time available to reach the peak. Running at faster speeds could increase the risk of developing Achilles tendinopathy and patellofemoral pain or limit recovery from these injuries without sufficient recovery.
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http://dx.doi.org/10.1111/sms.13972DOI Listing
April 2021

Synthetic glycolipid-based TLR4 antagonists negatively regulate TRIF-dependent TLR4 signalling in human macrophages.

Innate Immun 2021 Apr;27(3):275-284

School of Life Sciences, Anglia Ruskin University, UK.

TLRs, including TLR4, play a crucial role in inflammatory-based diseases, and TLR4 has been identified as a therapeutic target for pharmacological intervention. In previous studies, we investigated the potential of FP7, a novel synthetic glycolipid active as a TLR4 antagonist, to inhibit haematopoietic and non-haematopoietic MyD88-dependent TLR4 pro-inflammatory signalling. The main aim of this study was to investigate the action of FP7 and its derivative FP12 on MyD88-independent TLR4 signalling in THP-1 derived macrophages. Western blotting, Ab array and ELISA approaches were used to explore the effect of FP7 and FP12 on TRIF-dependent TLR4 functional activity in response to LPS and other endogenous TLR4 ligands in THP-1 macrophages. A different kinetic in the inhibition of endotoxin-driven TBK1, IRF3 and STAT1 phosphorylation was observed using different LPS chemotypes. Following activation of TLR4 by LPS, data revealed that FP7 and FP12 inhibited TBK1, IRF3 and STAT1 phosphorylation which was associated with down-regulation IFN-β and IP-10. Specific blockage of the IFN type one receptor showed that these novel molecules inhibited TRIF-dependent TLR4 signalling via IFN-β pathways. These results add novel information on the mechanism of action of monosaccharide FP derivatives. The inhibition of the TRIF-dependent pathway in human macrophages suggests potential therapeutic uses for these novel TLR4 antagonists in pharmacological interventions on inflammatory diseases.
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http://dx.doi.org/10.1177/17534259211005840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054148PMC
April 2021

Sex-Related Differences in Chronic Myeloid Neoplasms: From the Clinical Observation to the Underlying Biology.

Int J Mol Sci 2021 Mar 5;22(5). Epub 2021 Mar 5.

Division of Hematological Malignancies and Bone Marrow Transplantation, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA.

Chronic myeloid neoplasms are clonal diseases with variable clinical course and outcomes and despite the introduction of novel therapies, patients with high-risk disease continue to have overall poor outcomes. Different groups have highlighted that men have overall worse survival and higher incidence of transformation to acute leukemia compared to women across neoplasms such as myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), MDS/MPN overlap neoplasms, and CML. More recent studies evaluating the genomic profile of patients with these neoplasms demonstrated a male predominance for mutations in high-risk genes including , , and . The understanding of the underlying biology is limited but a number of hypotheses have been developed and are currently being investigated. This review summarizes the current knowledge about sex-related differences in the clinical outcomes and genomic profile of patients with chronic myeloid neoplasms and discusses the hypothesized biologic mechanisms as an attempt to explain these observations.
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http://dx.doi.org/10.3390/ijms22052595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961949PMC
March 2021

Common biomarkers of physiologic stress and associations with delirium in patients with intracerebral hemorrhage.

J Crit Care 2021 Mar 23;64:62-67. Epub 2021 Mar 23.

Department of Neurology, Brown University, Alpert Medical School, Providence, RI, USA.

Purpose: To examine associations between physiologic stress and delirium in the setting of a direct neurologic injury.

Materials And Methods: We obtained initial neutrophil-to-lymphocyte ratio (NLR), glucose, and troponin in consecutive non-comatose patients with non-traumatic intracerebral hemorrhage (ICH) over 1 year, then used multivariable regression models to determine associations between each biomarker and incident delirium. Delirium diagnoses were established using DSM-5-based methods, with exploratory analyses further categorizing delirium as first occurring <24 h ("early-onset") or > 24 h after presentation ("later-onset").

Results: Of 284 patients, delirium occurred in 55% (early-onset: 39% [n = 111]; later-onset: 16% [n = 46]). Patients with delirium had higher NLR (mean 9.0 ± 10.4 vs. 6.4 ± 5.5; p = 0.01), glucose (mean 146.5 ± 59.6 vs. 129.9 ± 41.4 mg/dL; p = 0.008), and a higher frequency of elevated troponin (>0.05 ng/mL; 21% vs. 10%, p = 0.02). In adjusted models, elevated NLR (highest quartile: OR 3.4 [95% CI 1.5-7.8]), glucose (>180 mg/dL: OR 3.1 [95% CI 1.1-8.2]), and troponin (OR 3.0 [95% CI 1.2-7.2]) were each associated with delirium, but only initial NLR was specifically associated with later-onset delirium and with delirium in non-mechanically ventilated patients.

Conclusions: Stress-related biomarkers corresponding to multiple organ systems are associated with ICH-related delirium. Early NLR elevation may also predict delayed-onset delirium, potentially implicating systemic inflammation as a contributory delirium mechanism.
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http://dx.doi.org/10.1016/j.jcrc.2021.03.009DOI Listing
March 2021

Large Granular Lymphocytosis With Cytopenias After Allogeneic Blood or Marrow Transplantation: Clinical Characteristics and Response to Immunosuppressive Therapy.

Transplant Cell Ther 2021 Mar 16;27(3):260.e1-260.e6. Epub 2020 Dec 16.

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address:

Large granular lymphocytosis (LGL)-or LGL leukemia-is a T- or NK-cell lymphoproliferative disorder that often results in cytopenias and autoimmune phenomena. Several studies have described LGL in a subset of patients after allogeneic blood or marrow transplantation (alloBMT), almost exclusively in the setting of asymptomatic lymphocytosis. Some have suggested an association with improved transplant-related outcomes. In contrast, clinically significant LGL after alloBMT is only described in small case reports. This study sought to assess the characteristics, significance, and response to treatment of LGL associated with unexplained anemia, thrombocytopenia, or neutropenia after alloBMT. We performed a retrospective analysis of 150 patients who were evaluated for LGL by peripheral blood flow cytometry (LGL flow) for unexplained cytopenias following initial engraftment after alloBMT from January 1 2012 to July 1, 2019. We identified patients with abnormally increased populations of LGL cells (LGL+) as assessed by Johns Hopkins Hematopathology. We collected demographic, transplantation, and LGL treatment information from electronic medical records. We compared LGL+ patients to patients with unexplained cytopenias with negative flow cytometry for LGL (LGL-) in this cohort. We also assessed change in blood counts after 4 weeks of immunosuppressive therapy in LGL+ patients. Cytopenias occurred at a median of 5.7 months (range 1-81) after alloBMT. The majority of the transplants were nonmyeloablative from haploidentical donors, and all patients received post-transplantation cyclophosphamide for graft-versus-host disease prophylaxis, consistent with the overall alloBMT characteristics at our center. We identified 70 patients with LGL and cytopenias, representing 47% of those evaluated by flow cytometry. There were no significant demographic or transplant-related differences between LGL+ patients and LGL- patients. The median age was 59, and 63% were male. LGL+ patients were more likely to have had cytomegalovirus (CMV) viremia (73% versus 28%, P < .0001), but not acute or chronic graft-versus-host disease. LGL+ patients had higher absolute lymphocyte counts (1500 versus 485/ mm, P < .0001), a trend toward lower absolute neutrophil count (660 versus 965/mm, P = .17), and lower neutrophil to lymphocyte ratio (0.39 versus 1.71, P < .001). There were no differences in overall survival or relapse-free survival. Of those with T-cell LGL, 45 were assessed for T-cell receptor clonality. In all, 22% were clonal, 53% oligoclonal, 4% polyclonal, and 20% indeterminate. Thirty (43%) LGL+ patients received immunosuppressive therapy (IST) for cytopenias. First-line treatment was corticosteroids for 25 (83%). Among those treated, there was an increase in median absolute neutrophil count from 720 before treatment to 1990/mm after 4 weeks (P = .0017). Thrombocytopenia and anemia showed at most a mild improvement with IST. LGL was a common association with otherwise unexplained cytopenias after alloBMT, almost always after prior CMV infection. LGL in the setting of cytopenias did not predict improved transplantation outcomes compared to those with cytopenias without presence of LGL. IST was effective at improving neutropenia associated with LGL after alloBMT.
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http://dx.doi.org/10.1016/j.jtct.2020.12.008DOI Listing
March 2021

Association of CSF Alzheimer's disease biomarkers with postoperative delirium in older adults.

Alzheimers Dement (N Y) 2021 17;7(1):e12125. Epub 2021 Mar 17.

Aging Brain Center, Institute for Aging Research Hebrew SeniorLife Boston Massachusetts USA.

Introduction: The interaction between delirium and dementia is complex. We examined if Alzheimer's disease (AD) biomarkers in patients without clinical dementia are associated with increased risk of postoperative delirium, and whether AD biomarkers demonstrate a graded association with delirium severity.

Methods: Participants ( = 59) were free of clinical dementia, age 70 years, and scheduled for elective total knee or hip arthroplasties. Cerebrospinal fluid (CSF) was collected at the time of induction for spinal anesthesia. CSF AD biomarkers were measured by enzyme-linked immunosorbent assay (ELISA) (ADX/Euroimmun); cut points for amyloid, tau, and neurodegeneration (ATN) biomarker status were  = amyloid beta (Aβ) <175 pg/mL or Aβ ratio <0.07;  = p-tau >80 pg/mL; and  = t-tau >700 pg/mL. Confusion Assessment Method (CAM) and CAM-Severity (CAM-S) were rated daily post-operatively for delirium and delirium severity, respectively.

Results: Aβ, tau, and p-tau mean pg/mL (SD) were 361.5 (326.1), 618.3 (237.1), and 97.1 (66.1), respectively, for those with delirium, and 550.4 (291.6), 518.3 (213.5), and 54.6 (34.5), respectively, for those without delirium. Thirteen participants (22%) were ATN positive. Delirium severity by peak CAM-S [mean difference (95% confidence interval)] was 1.48 points higher (0.29-2.67),  = 0.02 among the ATN positive. Delirium in the ATN-positive group trended toward but did not reach statistical significance (23% vs. 7%, p = 0.10). Peak CAM-S [mean (SD)] in the delirium group was 7 (2.8) compared to no delirium group 2.5 (1.3), but when groups were further classified by ATN status, an incremental effect on delirium severity was observed, such that patients who were both ATN and delirium negative had the lowest mean (SD) peak CAM-S scores of 2.5 (1.3) points, whereas those who were ATN and delirium positive had CAM-S scores of 8.7 (2.3) points; other groups (either ATN or delirium positive) had intermediate CAM-S scores.

Discussion: The presence of AD biomarkers adds important information in predicting delirium severity. Future studies are needed to confirm this relationship and to better understand the role of AD biomarkers, even in pre-clinical phase, in delirium.
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http://dx.doi.org/10.1002/trc2.12125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968120PMC
March 2021

RCVS president must meet 'Nolan principles'.

Vet Rec 2021 03;188(6):230

School House, Marloes, Haverfordwest, Dyfed, SA62 3BQ.

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http://dx.doi.org/10.1002/vetr.331DOI Listing
March 2021

Are there common walking gait characteristics in patients diagnosed with late-onset Pompe disease?

Hum Mov Sci 2021 Jun 14;77:102777. Epub 2021 Mar 14.

Human Movement and Rehabilitation, School of Health and Society, University of Salford, Salford, UK.

Late-onset Pompe disease (LOPD) is a rare disease, defined as a progressive accumulation of lysosomal glycogen resulting in muscle weakness and respiratory problems. Anecdotally, individuals often have difficulties walking, yet, there is no three-dimensional data supporting these claims. We aimed to assess walking patterns in individuals with LOPD and compare with healthy individuals. Kinematic, kinetic and spatiotemporal data were compared during walking at a self-selected speed between individuals with LOPD (n = 12) and healthy controls (n = 12). Gait profile scores and movement analysis profiles were also determined to indicate gait quality. In comparison with healthy individuals, the LOPD group demonstrated greater thoracic sway (96%), hip adduction angles (56%) and pelvic range of motion (77%) and reduced hip extensor moments (36%). Greater group variance for the LOPD group were also observed. Individuals with LOPD had a slower (15%) walking speed and reduced cadence (7%). Gait profile scores were 37% greater in the LOPD group compared to the healthy group. Proximal muscular weakness associated with LOPD disease is likely to have resulted in a myopathic gait pattern, slower selected walking speeds and deviations in gait patterns. Although individuals with LOPD presented with some common characteristics, greater variability in gait patterns is likely to be a result of wide variability in phenotype spectrum observed with LOPD. This is the first study to examine walking in individuals with LOPD using instrumented gait analysis and provides an understanding of LOPD on walking function which can help orientate physiotherapy treatment for individuals with LOPD.
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http://dx.doi.org/10.1016/j.humov.2021.102777DOI Listing
June 2021

Effects of intermittent claudication due to arterial disease on pain-free gait.

Clin Biomech (Bristol, Avon) 2021 Mar 2;83:105309. Epub 2021 Mar 2.

Centre for Health, Sport and Rehabilitation Sciences Research, University of Salford, Salford, UK; School of Health & Society, University of Salford, Salford, UK. Electronic address:

Introduction: Studies of intermittent claudication gait report inconsistent outcomes. Changes in gait are often attributed to degradation of calf muscles, but causation has not been proven through real-time electromyographic data. Neither have effects of walking speed been fully considered. This study aimed to investigate the effect of intermittent claudication on kinematics, kinetics and muscle activity during pain-free gait.

Methods: 18 able bodied individuals and 18 with intermittent claudication walked at their preferred speed while lower limb kinematic, kinetic and electromyography data were collected.

Findings: People with intermittent claudication walk slower and with reduced step length. Internal ankle plantarflexion moment (P = 0.004, effect size = 0.96) and ankle power generation (P < 0.001, effect size = 1.36) in late stance were significantly reduced for individuals with intermittent claudication. Significant moment and power reductions at the knee and power reduction at hip occurred in early stance, with similar reductions in early and late stance for ground reaction forces. Peak electromyography of soleus activity was significantly reduced in late stance (P = 0.01, effect size = 1.1, n = 13). Effects were independent of walking speed.

Interpretation: Reductions in ankle plantarflexion moments and power generation were consistent with reduced soleus electromyography activity and reduced peak vertical ground reaction forces during late stance. These effects are not due to a reduced walking speed. Changes in knee and hip function are also unrelated to walking speed. These outcomes provide a platform for the design and evaluation of interventions that seek to restore normal walking and improve pain-free walking distances for people with intermittent claudication.
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http://dx.doi.org/10.1016/j.clinbiomech.2021.105309DOI Listing
March 2021

Effect of Volitional Effort on Submental Surface Electromyographic Activity During Healthy Swallowing.

Dysphagia 2021 Mar 9. Epub 2021 Mar 9.

The University of Canterbury Rose Centre for Stroke Recovery and Research, Christchurch, New Zealand.

The effortful swallowing technique aims to compensate for or rehabilitate impaired swallowing by using maximal volitional effort to behaviorally modify aspects of swallowing physiology. Given that swallowing is a submaximal task, swallowing at submaximal levels has recently been suggested as a more task-specific therapeutic technique. The aim of this study was to investigate differences in muscle activity during minimum, regular, and maximum effort swallowing of different boluses and across different ages, with the goal of characterizing the task specificity of minimum effort and maximum effort swallowing. Forty-three healthy adults (22 female) representing four age groups (20-39, 40-59, 60-79, and 80 + years) participated in the study. They were verbally cued to swallow saliva and 5 mL water boluses using participant-determined minimum, regular, and maximum levels of effort, in randomized order. sEMG peak amplitude and duration of each swallow were measured. Linear mixed effects analyses demonstrated that compared to regular effort swallowing, maximum effort swallowing resulted in increased sEMG amplitude (p < .001) and prolonged duration (p < .001), while minimum effort swallowing resulted in decreased amplitude (p < .001) but no significant difference in duration (p = .06). These effects occurred regardless of age or bolus type. Differences in sEMG activity were smaller between regular and minimum effort swallowing than regular and maximum effort swallowing. Both increasing and decreasing volitional efforts during swallowing translate to significant modulation of muscle activity. However, regular swallowing is more similar to minimal effort swallowing. Results reinforce the concept of swallowing as a submaximal task, and provide insight into the development of sEMG biofeedback techniques for rehabilitation.
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http://dx.doi.org/10.1007/s00455-021-10278-4DOI Listing
March 2021

Somatic Mutations and the Risk of Undifferentiated Autoinflammatory Disease in MDS: An Under-Recognized but Prognostically Important Complication.

Front Immunol 2021 19;12:610019. Epub 2021 Feb 19.

National Institute for Health Research-Leeds Biomedical Research Centre and Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), Wellcome Trust Brenner Building, St James's University Hospital, Leeds, United Kingdom.

We theorized that myelodysplastic syndrome (MDS) with somatic mutations and karyotype abnormalities are associated with autoinflammation, and that the presence of autoinflammatory disease affected prognosis in MDS. One hundred thirty-four MDS patients were assessed for the prevalence of autoinflammatory complications and its link with karyotypes and somatic mutation status. Autoinflammatory complications were described either as well-defined autoinflammatory diseases (AD) or undifferentiated "autoinflammatory disease" (UAD) (defined as CRP over 10.0 mg/L on five consecutive occasions, taken at separate times and not explained by infection). Several patient characteristics including demographic, clinical, laboratory, cytogenetics charts, and outcomes, were compared between different groups. Sixty-two (46.3%) patients had an autoinflammatory complication manifesting as arthralgia (43.5% . 23.6%, = 0.0146), arthritis (30.6% . 15.3%, = 0.0340), skin rash (27.4% . 12.5%, = 0.0301), pleuritis (14.5% . 4.2%, = 0.0371) and unexplained fever (27.4% . 0%, < 0.0001). AD were found in 7.4% of MDS patients (with polymyalgia rheumatic being the most frequently one). Classical autoimmune diseases were found only in 4 MDS patients (3.0%). Transcription factor pathway mutations () (OR 2.20 [95%CI 1.02-4.75], = 0.0451) and abnormal karyotypes (OR 2.76 [95%CI 1.22-6.26], = 0.0153) were associated with autoinflammatory complications. Acute leukaemic transformation was more frequent in MDS patients with autoinflammatory features than those without (27.4% . 9.7%, = 0.0080). Autoinflammatory complications are common in MDS. Somatic mutations of transcription factor pathways and abnormal karyotypes are associated with greater risk of autoinflammatory complications, which are themselves linked to malignant transformation and a worse prognosis.
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http://dx.doi.org/10.3389/fimmu.2021.610019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933213PMC
February 2021

Pain Experiences of Adults With Sickle Cell Disease and Hematopoietic Stem Cell Transplantation: A Qualitative Study.

Pain Med 2021 Mar 1. Epub 2021 Mar 1.

Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

Objective: Despite increasing use of hematopoietic stem cell transplantation (HSCT) for adults with sickle cell disease (SCD), little is known about pain management experiences throughout this process. The objective of this study was to explore patients' experiences with pain and pain management during and after HSCT for SCD.

Methods: We conducted a qualitative interview study with 10 patients who underwent HSCT for SCD. We transcribed interviews verbatim and inductively identified codes. We used thematic analysis alongside a constant comparative method to develop and refine a codebook that aided in the identification of themes.

Results: Four key themes emerged. (1) The pain trajectory: patients described a fluctuating course of pain during HSCT, which often extended long afterwards and impacted all aspects of life, particularly affected by pre-HSCT experiences; (2) The role of opioids-a double-edged sword: patients described opioids as reducing pain but insufficiently to balance significant adverse effects and burden; (3) Patient-centered decision making in pain management: patients described insufficient agency in decisions about opioid use and weaning; and (4) Consequences of health-related stigma: patients described experiences with stigma, mainly related to opioid use and weaning, as similar to pre-HSCT.

Conclusions: From the perspective of patients who have undergone HSCT for SCD, clinicians should use a patient-centered approach, integrating non-opioid approaches into pain management, particularly psychosocial support. As transplant for SCD becomes increasingly available, incorporating patient perspectives may improve health care delivery and overall patient experiences.
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http://dx.doi.org/10.1093/pm/pnaa464DOI Listing
March 2021

Relationship of donor age and relationship to outcomes of haploidentical transplantation with posttransplant cyclophosphamide.

Blood Adv 2021 03;5(5):1360-1368

Department of Oncology and.

Allogeneic blood or marrow transplantation (BMT) physicians seek to optimize all possible variables to improve outcomes. Selectable factors include conditioning, graft-versus-host disease (GVHD) prophylaxis, graft source, and donor. Many patients, especially those with eligible haploidentical (haplo) donors, will have multiple donor options. We seek to identify factors to optimize the choice of haplo donors when using posttransplantation cyclophosphamide (PTCy) GVHD prophylaxis. We evaluated the effect of modifiable donor characteristics (donor age and relationship) on outcomes following haplo BMT with a uniform nonmyeloablative conditioning and PTCy. From 2002 to 2017, 889 consecutive adult patients underwent nonmyeloablative haplo BMT with PTCy. Median follow-up among survivors was 2.5 years after BMT. Median recipient age was 59 (range: 18 to 76) years and median donor age was 40 (range: 13 to 79) years. Multivariable analyses demonstrated that increasing donor age by decade was associated with poorer overall survival (hazard ratio [HR], 1.13 [1.05, 1.22; P = .0015]), worse progression-free survival (HR, 1.09 [1.02, 1.16; P = .015]), and a higher risk for grade 2 to 4 and grade 3 to 4 GVHD (1.3 [1.06, 1.61; P = .013]), but not for chronic GVHD (HR, 1.06 [0.94, 1.2]; P = .37). These less-favorable results with older donors were attributable to worse nonrelapse mortality (HR, 1.19 [1.05, 1.34]; P = .006), not relapse. Parents were associated with inferior outcomes compared with sibling donors, whereas no significant differences were observed between parental donors. These data suggest that the youngest, adult-sized donors should be preferred when multiple haplo donors are available.
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http://dx.doi.org/10.1182/bloodadvances.2020003922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948266PMC
March 2021

Androgen receptor-reduced sensitivity is associated with increased mortality and poorer glycaemia in men with type 2 diabetes mellitus: a prospective cohort study.

Cardiovasc Endocrinol Metab 2021 Mar 18;10(1):37-44. Epub 2020 Aug 18.

Centre for Diabetes and Endocrinology, Barnsley Hospital, Barnsley.

Introduction: Hypogonadism is associated with poorer glycaemic outcomes/increased all-cause and cardiovascular morbidity/mortality in type 2 diabetes mellitus (T2DM). Increasing CAG repeat number within exon-1 of the androgen receptor (AR) gene is associated with increased AR resistance/insulin resistance.

Methods: We determined in a long-term 14-year follow-up cohort of 423 T2DM Caucasian men, the association between baseline androgen status/CAG repeat number (by PCR then Sequenom sequencing) and metabolic/cardiovascular outcomes.

Results: : Lower total testosterone was associated with higher BMI (kg/m) at 14-year-follow-up: regression coefficient -0.30 (95% confidence interval -0.445 to -0.157), = 0.0001. The range of CAG repeat number was 9-29 repeats. Higher CAG repeat number in exon-1 of the AR gene was associated with higher follow-up HbA1c2016 - each unit increase in CAG repeat-associated with an increment of 0.1% in HbA1C2016 ( = 0.04), independent of baseline testosterone. : At an average of 14-year-follow-up, 55.8% of hypogonadal men had died vs 36.1% of eugonadal men ( = 0.001). There was a 'u' shaped relation between number of CAG repeats and mortality. Twenty-one CAG repeats were associated with an up to nearly 50% lower mortality rate than <21 CAG repeats and >21 CAG repeats - independent of baseline testosterone level.

Conclusion: A higher number of CAG repeats at the AR gene associates with higher future HbA1c. There was a 'u' shaped relation between CAG repeat number and mortality rate. Determination of CAG repeat number may become part of assessment of androgen status/its consequences for men with T2DM.
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http://dx.doi.org/10.1097/XCE.0000000000000230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901820PMC
March 2021

One-Year Medicare Costs Associated With Delirium in Older Patients Undergoing Major Elective Surgery.

JAMA Surg 2021 May;156(5):430-442

Aging Brain Center, Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts.

Importance: Delirium is a common, serious, and potentially preventable problem for older adults, associated with adverse outcomes. Coupled with its preventable nature, these adverse sequelae make delirium a significant public health concern; understanding its economic costs is important for policy makers and health care leaders to prioritize care.

Objective: To evaluate current 1-year health care costs attributable to postoperative delirium in older patients undergoing elective surgery.

Design, Setting, And Participants: This prospective cohort study included 497 patients from the Successful Aging after Elective Surgery (SAGES) study, an ongoing cohort study of older adults undergoing major elective surgery. Patients were enrolled from June 18, 2010, to August 8, 2013. Eligible patients were 70 years or older, English-speaking, able to communicate verbally, and scheduled to undergo major surgery at 1 of 2 Harvard-affiliated hospitals with an anticipated length of stay of at least 3 days. Eligible surgical procedures included total hip or knee replacement; lumbar, cervical, or sacral laminectomy; lower extremity arterial bypass surgery; open abdominal aortic aneurysm repair; and open or laparoscopic colectomy. Data were analyzed from October 15, 2019, to September 15, 2020.

Exposures: Major elective surgery and hospitalization.

Main Outcomes And Measures: Cumulative and period-specific costs (index hospitalization, 30-day, 90-day, and 1-year follow-up) were examined using Medicare claims and extensive clinical data. Total inflation-adjusted health care costs were determined using data from Medicare administrative claims files for the 2010 to 2014 period. Delirium was rated using the Confusion Assessment Method. We also examined whether increasing delirium severity was associated with higher cumulative and period-specific costs. Delirium severity was measured with the Confusion Assessment Method-Severity long form. Regression models were used to determine costs associated with delirium after adjusting for patient demographic and clinical characteristics.

Results: Of the 566 patients who were eligible for the study, a total of 497 patients (mean [SD] age, 76.8 [5.1] years; 281 women [57%]; 461 White participants [93%]) were enrolled after exclusion criteria were applied. During the index hospitalization, 122 patients (25%) developed postoperative delirium, whereas 375 (75%) did not. Patients with delirium had significantly higher unadjusted health care costs than patients without delirium (mean [SD] cost, $146 358 [$140 469] vs $94 609 [$80 648]). After adjusting for relevant confounders, the cumulative health care costs attributable to delirium were $44 291 (95% CI, $34 554-$56 673) per patient per year, with the majority of costs coming from the first 90 days: index hospitalization ($20 327), subsequent rehospitalizations ($27 797), and postacute rehabilitation stays ($2803). Health care costs increased directly and significantly with level of delirium severity (none-mild, $83 534; moderate, $99 756; severe, $140 008), suggesting an exposure-response relationship. The adjusted mean cumulative costs attributable to severe delirium were $56 474 (95% CI, $40 927-$77 440) per patient per year. Extrapolating nationally, the health care costs attributable to postoperative delirium were estimated at $32.9 billion (95% CI, $25.7 billion-$42.2 billion) per year.

Conclusions And Relevance: These findings suggest that the economic outcomes of delirium and severe delirium after elective surgery are substantial, rivaling costs associated with cardiovascular disease and diabetes. These results highlight the need for policy imperatives to address delirium as a large-scale public health issue.
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http://dx.doi.org/10.1001/jamasurg.2020.7260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905699PMC
May 2021

Antibacterial Thiamine inspired silver (I) and gold (I) N-heterocyclic carbene compounds.

Inorganica Chim Acta 2021 Mar 27;517. Epub 2020 Nov 27.

Department of Chemistry, The University of Texas at Austin.

Three new coinage metal carbene complexes of silver and gold were synthesized from a thiamine inspired ligand. The compounds were characterized by HRMS, NMR spectroscopy (H, F, P and C), FT-IR and elemental analysis. The coordination environment around the metal centers was correlated to the diffusion coefficients obtained from DOSY-NMR experiments and was in agreement with the nuclearity observed in the solid-state by single crystal X-ray crystallography. The silver and gold carbene compounds were subjected to MIC studies against a panel of pathogenic bacteria, including multidrug resistant strains, with the gold carbene derivative showing the most potent antimicrobial activity against Gram-positive methicillin resistant (MRSA).
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http://dx.doi.org/10.1016/j.ica.2020.120152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869835PMC
March 2021

Human neurons from Christianson syndrome iPSCs reveal mutation-specific responses to rescue strategies.

Sci Transl Med 2021 Feb;13(580)

Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA.

Christianson syndrome (CS), an X-linked neurological disorder characterized by postnatal attenuation of brain growth (postnatal microcephaly), is caused by mutations in , the gene encoding endosomal Na/H exchanger 6 (NHE6). To hasten treatment development, we established induced pluripotent stem cell (iPSC) lines from patients with CS representing a mutational spectrum, as well as biologically related and isogenic control lines. We demonstrated that pathogenic mutations lead to loss of protein function by a variety of mechanisms: The majority of mutations caused loss of mRNA due to nonsense-mediated mRNA decay; however, a recurrent, missense mutation (the G383D mutation) had both loss-of-function and dominant-negative activities. Regardless of mutation, all patient-derived neurons demonstrated reduced neurite growth and arborization, likely underlying diminished postnatal brain growth in patients. Phenotype rescue strategies showed mutation-specific responses: A gene transfer strategy was effective in nonsense mutations, but not in the G383D mutation, wherein residual protein appeared to interfere with rescue. In contrast, application of exogenous trophic factors (BDNF or IGF-1) rescued arborization phenotypes across all mutations. These results may guide treatment development in CS, including gene therapy strategies wherein our data suggest that response to treatment may be dictated by the class of mutation.
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http://dx.doi.org/10.1126/scitranslmed.aaw0682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888381PMC
February 2021

The modern reverse shoulder arthroplasty and an updated systematic review for each complication: part II.

JSES Int 2021 Jan 10;5(1):121-137. Epub 2020 Sep 10.

ASES Multicenter Taskforce for RSA Complications, Rosemont, IL, USA.

Background: Globally, reverse shoulder arthroplasty (RSA) has moved away from the Grammont design to modern prosthesis designs. The purpose of this study was to provide a focused, updated systematic review for each of the most common complications of RSA by limiting each search to publications after 2010. In this part II, the following were examined: (1) instability, (2) humerus/glenoid fracture, (3) acromial/scapular spine fractures (AF/SSF), and (4) problems/miscellaneous.

Methods: Four separate PubMed database searches were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Overall, 137 studies for instability, 94 for humerus/glenoid fracture, 120 for AF/SSF, and 74 for problems/miscellaneous were included in each review, respectively. Univariate analysis was performed with chi-square and Fisher exact tests.

Results: The Grammont design had a higher instability rate vs. all other designs combined (4.0%, 1.3%; < .001), and the onlay humerus design had a lower rate than the lateralized glenoid design (0.9%, 2.0%;  = .02). The rate for intraoperative humerus fracture was 1.8%; intraoperative glenoid fracture, 0.3%; postoperative humerus fracture, 1.2%; and postoperative glenoid fracture, 0.1%. The rate of AF/SSF was 2.6% (371/14235). The rate for complex regional pain syndrome was 0.4%; deltoid injury, 0.1%; hematoma, 0.3%; and heterotopic ossification, 0.8%.

Conclusions: Focused systematic reviews of recent literature with a large volume of shoulders demonstrate that using non-Grammont modern prosthesis designs, complications including instability, intraoperative humerus and glenoid fractures, and hematoma are significantly reduced compared with previous studies. As the indications continue to expand for RSA, it is imperative to accurately track the rate and types of complications in order to justify its cost and increased indications.
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http://dx.doi.org/10.1016/j.jseint.2020.07.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846704PMC
January 2021

Predictive Low-Glucose Suspend Necessitates Less Carbohydrate Supplementation to Rescue Hypoglycemia: Need to Revisit Current Hypoglycemia Treatment Guidelines.

Diabetes Technol Ther 2021 Feb 18. Epub 2021 Feb 18.

Eli Lilly and Company, Cambridge, Massachusetts, USA.

Current guidelines recommend 15-20 g of carbohydrate (CHO) for treatment of mild to moderate hypoglycemia. However, these guidelines do not account for reduced insulin during suspensions with predictive low-glucose suspend (PLGS). We assessed insulin suspensions, hypoglycemic events, and CHO treatment during a 20-h inpatient evaluation of an investigational system with a PLGS feature, including an overnight basal up-titration period to activate the PLGS. Among 10 adults with type 1 diabetes, there were 59 suspensions; 7 suspensions were associated with rescue CHO and 5 with hypoglycemia. Rescue treatment consisted of median 9 g CHO (range: 5-16 g), with no events requiring repeat CHO. No rescue CHO were given during or after insulin suspension for the overnight basal up-titration. To minimize rebound hyperglycemia and needless calorie intake from hypoglycemia overtreatment, updated guidance for PLGS systems should reflect possible need to reduce CHO amounts for hypoglycemia rescue associated with an insulin suspension. The clinical trial was registered with ClinicalTrials.gov (NCT03890003).
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http://dx.doi.org/10.1089/dia.2020.0619DOI Listing
February 2021

Double unrelated umbilical cord blood vs HLA-haploidentical bone marrow transplantation: the BMT CTN 1101 trial.

Blood 2021 01;137(3):420-428

Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN.

Results of 2 parallel phase 2 trials of transplantation of unrelated umbilical cord blood (UCB) or bone marrow (BM) from HLA-haploidentical relatives provided equipoise for direct comparison of these donor sources. Between June 2012 and June 2018, 368 patients aged 18 to 70 years with chemotherapy-sensitive lymphoma or acute leukemia in remission were randomly assigned to undergo UCB (n = 186) or haploidentical (n = 182) transplant. Reduced-intensity conditioning comprised total-body irradiation with cyclophosphamide and fludarabine for both donor types. Graft-versus-host disease prophylaxis for UCB transplantation was cyclosporine and mycophenolate mofetil (MMF) and for haploidentical transplantation, posttransplant cyclophosphamide, tacrolimus, and MMF. The primary end point was 2-year progression-free survival (PFS). Treatment groups had similar age, sex, self-reported ethnic origin, performance status, disease, and disease status at randomization. Two-year PFS was 35% (95% confidence interval [CI], 28% to 42%) compared with 41% (95% CI, 34% to 48%) after UCB and haploidentical transplants, respectively (P = .41). Prespecified analysis of secondary end points recorded higher 2-year nonrelapse mortality after UCB, 18% (95% CI, 13% to 24%), compared with haploidentical transplantation, 11% (95% CI, 6% to 16%), P = .04. This led to lower 2-year overall survival (OS) after UCB compared with haploidentical transplantation, 46% (95% CI, 38-53) and 57% (95% CI 49% to 64%), respectively (P = .04). The trial did not demonstrate a statistically significant difference in the primary end point, 2-year PFS, between the donor sources. Although both donor sources extend access to reduced-intensity transplantation, analyses of secondary end points, including OS, favor haploidentical BM donors. This trial was registered at www.clinicaltrials.gov as #NCT01597778.
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http://dx.doi.org/10.1182/blood.2020007535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819761PMC
January 2021

Evaluation and Management of Common Accessory Ossicles of the Foot and Ankle in Children and Adolescents.

J Am Acad Orthop Surg 2021 04;29(7):e312-e321

From the Department of Orthopaedics and Physical Medicine (Murphy and Van Nortwick), Medical University of South Carolina, Charleston, SC, the Department of Radiology (Jones), Medical University of South Carolina, Charleston, SC, and the Shriner's Hospital for Children (Moone), Springfield, MA.

Accessory ossicles are a common radiographic finding about the foot and ankle in children and adolescents. They are often noted incidentally during evaluation of foot and ankle injuries, and most can be managed nonsurgically. Although over 20 accessory ossicles have been described around the foot and ankle, five specific structures generate the most concern in pediatric patients. An accessory navicular presents commonly with medial midfoot pain and may require surgical intervention after failure of nonsurgical treatment. Although an accessory navicular can be treated surgically with simple excision, there is some recent evidence that supports concomitant reconstruction of associated flatfoot deformities. Os trigonum, an ossicle posterior to the talus, is also commonly asymptomatic. However, os trigonum may be associated with persistent posterior ankle pain, and open and endoscopic resection techniques are successful. Os subfibulare is an uncommon ossicle that may be associated with recurrent ankle sprains. Recent literature reports successful return to activities after ossicle excision and ligament reconstruction. Os subtibiale may be confused with a medial malleolar fracture in skeletally immature patients. Os peroneum may contribute to lateral midfoot pain.
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http://dx.doi.org/10.5435/JAAOS-D-20-00218DOI Listing
April 2021

Current process and outcomes of the surgical management of LUTS due to benign prostatic enlargement: how consistent are we? - results from the multi-institutional audit of surgical management of BPE (AuSuM BPE) in the United Kingdom.

Scott Med J 2021 May 17;66(2):58-65. Epub 2021 Jan 17.

Consultant Urological Surgeon, Department of Urology, Salford Royal NHS Foundation Trust, UK.

Objective: In view of changing landscape of surgical treatment for LUTS secondary to BPE, this audit was undertaken to assess key aspects of the processes and outcomes of the current interventional treatments for BPE, across different units in the UK.

Materials And Method: A multi-institutional snapshot audit was conducted for patients undergoing interventions for LUTS/BPE over 8-week period. Using Delphi process two-part proforma was designed to capture data.

Results: 529 patients were included across 20 NHS trusts in England and Wales. Median age was 73 years. Indications for surgery were acute retention (47%) and LUTS (45%). 80% of patients had prior medical therapy. TURP formed the commonest procedure. 27% patients had <23 hour hospital stay. Immediate (21%) and delayed (18%) complications were Clavien-Dindo <2 category. High proportion of patients reported residual symptoms. Type and indication of surgery were significant predictor of complications, length of stay and failure of TWOC outcomes, on multivariate analyses. There were variations in departmental processes, 50% centres used PROMs.

Conclusion: Monopolar TURP still remains the commonest intervention for BPE. Most departments are adopting newer technologies. The audit identified opportunities for development of consistent, effective and patient centric practices as well as need for large-scale focused studies.
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http://dx.doi.org/10.1177/0036933020977295DOI Listing
May 2021

Classification of Stroke Patients With Dysphagia Into Subgroups Based on Patterns of Submental Muscle Strength and Skill Impairment.

Arch Phys Med Rehabil 2021 05 22;102(5):895-904. Epub 2020 Dec 22.

University of Canterbury Rose Centre for Stroke Recovery and Research, Christchurch, New Zealand; School of Psychology, Speech and Hearing, University of Canterbury, Christchurch, New Zealand.

Objectives: To identify and characterize subgroups of stroke patients with clinical signs of dysphagia, based on swallowing-related strength and skill impairments of the submental muscle group.

Design: Prospective observational study.

Setting: Inpatient rehabilitation centers and community dwellings.

Participants: Individuals (N=114), including stroke patients with dysphagia (n=55) and 2 control groups including myopathic patients with dysphagia (n=19) and healthy volunteers (n=40) were included in this study.

Interventions: Not applicable.

Main Outcome Measures: Novel clinical assessment of strength (force generation) and skill (spatial and temporal precision of muscle activation) of the submental muscle group during swallowing and nonswallowing behaviors, using surface electromyography and dynamometry.

Results: Hierarchical cluster analysis revealed 4 clusters, which could be broadly characterized as cluster 1: intact strength and skill, cluster 2: poor strength and poor nonswallowing skill, cluster 3: poor strength, and cluster 4: poor strength and poor swallowing skill. Membership in cluster was significantly associated with medical diagnosis (P<.001). The majority of healthy and myopathic participants were assigned to clusters 1 and 3, respectively, whereas stroke patients were found in all 4 clusters. Skill outcome measures were more predictive of cluster assignment than strength measures.

Conclusions: Although healthy and myopathic participants demonstrated predominantly homogeneous swallowing patterns of submental muscle function within their etiology, several subgroups were identified within stroke, possibly reflecting different subtypes of swallowing function. Future research should focus on the nature and rehabilitation needs of these subtypes. Assessment of skill in swallowing may be an important but overlooked aspect of rehabilitation.
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http://dx.doi.org/10.1016/j.apmr.2020.11.014DOI Listing
May 2021