Acute Lower Extremity Fracture Management in Chronic Spinal Cord Injury: 2022 Delphi Consensus Recommendations.

Our objective was to develop a clinical practice guideline (CPG) for the treatment of acute lower extremity fractures in persons with a chronic spinal cord injury (SCI). Methods: Information from a previous systematic review that addressed lower extremity fracture care in persons with an SCI as well as information from interviews of physical and occupational therapists, searches of the literature, and expert opinion were used to develop this CPG. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to determine the quality of evidence and the strength of the recommendations. An overall GRADE quality rating was applied to the evidence. Conclusions: Individuals with a chronic SCI who sustain an acute lower extremity fracture should be provided with education regarding the risks and benefits of operative and nonoperative management, and shared decision-making for acute fracture management should be used. Nonoperative management historically has been the default preference; however, with the advent of greater patient independence, improved surgical techniques, and advanced therapeutics and rehabilitation, increased use of surgical management should be considered. Physical therapists, kinesiotherapists, and/or occupational therapists should assess equipment needs, skills training, and caregiver assistance due to changes in mobility resulting from a lower extremity fracture. Therapists should be involved in fracture management as soon as possible following fracture identification. Pressure injuries, compartment syndrome, heterotopic ossification, nonunion, malunion, thromboembolism, pain, and autonomic dysreflexia are fracture-related complications that clinicians caring for patients who have an SCI and a lower extremity fracture may encounter. Strategies for their treatment are discussed. The underlying goal is to return the patient as closely as possible to their pre-fracture functional level with operative or nonoperative management.

The impact of a fellow on a regional robotic-assisted partial nephrectomy service.

INTRODUCTION: Training a fellow has a cost in time and effort for the surgeon and their team. Their relative inexperience may also negatively affect the patient. The aim of this study was to determine and quantify the impact of a fellow on a regional robotic-assisted partial nephrectomy service and on perioperative outcomes. MATERIALS AND METHODS: We reviewed the prospectively collected data for 522 patients who had undergone robotic-assisted partial nephrectomy since 2015 during the tenure of six fellows. Perioperative outcomes for three groups were compared: group A (no fellow participation), group B (some participation) and group C (fellow completed entire operation). We also reviewed progression over 12 months. RESULTS: Demographics were similar in all groups apart from the percentage of men, which was lower in group C (p < 0.05). Operative time was 27 minutes longer for group B (p < 0.001). Warm ischaemia time was significantly shorter for group A but the difference was only four minutes (p < 0.001). Length of stay was slightly shorter for group C compared with the other groups (p < 0.01). Trifecta achievement was greatest for group A (p < 0.001). There were no perioperative deaths in any group and positive margins, complications and readmissions were low and similar in all groups. Towards the end of their fellowship, fellows performed more operations independently. CONCLUSION: There is a measurable, but small, negative impact of a fellow on a robotic-assisted partial nephrectomy service, which reduces with experience. With appropriate supervision and patient selection, a fellow can be taught robotic-assisted partial nephrectomy without affecting patient safety or treatment outcome.

Congruence and trajectories of device-measured and self-reported physical activity during therapy for early breast cancer.

PURPOSE: This study examines congruence between self-reported and device-measured physical activity data in women with early breast cancer and compares trajectories under different treatments. METHODS: Women with non-metastatic breast cancer were recruited before primary therapy. In four weeks distributed over six months after treatment start, patients reported time spent on work, transport, chores and sports via diary and wore Garmin® vivofit 3 accelerometers to assess steps taken. Associations between these measures and agreement regarding guideline adherence were tested with Spearman's Correlation Coefficient and Weighted Kappa statistic. Effects of time and treatment were evaluated using mixed analyses of variance. RESULTS: Ninety-nine participants (median age = 50) were treated with adjuvant (N = 23), neoadjuvant (N = 21) or without chemotherapy (N = 55). Coherence between self-report and device data was strong (r = 0.566). Agreement about reaching recommendations was only "fair" (kappa coefficient = 0.321 and 0.249, resp.). Neither treatment or week nor their interaction had effects on step counts (all p > 0.05). Self-reported activity time was lower for patients with chemotherapy than for those without (adjuvant: ∆ = 69min, p = 0.006, neoadjuvant: ∆ = 45min, p = 0.038) and lower in week 18 than in week 3 (∆ = 43min, p = 0.010). CONCLUSION: Results show that consumer-grade activity monitors and self-reports correlate but show different perspectives on physical activity in breast cancer patients. In general, patients perceive some decline regardless of primary treatment regimen. Those affected should be offered assistance to gain the benefits of activity. Accelerometers may help professionals to identify these individuals and patients to verify appraisal of their activity levels.

The transCampus Metabolic Training Programme Explores the Link of SARS-CoV-2 Virus to Metabolic Disease.

Currently, we are experiencing a true pandemic of a communicable disease by the virus SARS-CoV-2 holding the whole world firmly in its grasp. Amazingly and unfortunately, this virus uses a metabolic and endocrine pathway via ACE2 to enter our cells causing damage and disease. Our international research training programme funded by the German Research Foundation has a clear mission to train the best students wherever they may come from to learn to tackle the enormous challenges of diabetes and its complications for our society. A modern training programme in diabetes and metabolism does not only involve a thorough understanding of classical physiology, biology and clinical diabetology but has to bring together an interdisciplinary team. With the arrival of the coronavirus pandemic, this prestigious and unique metabolic training programme is facing new challenges but also new opportunities. The consortium of the training programme has recognized early on the need for a guidance and for practical recommendations to cope with the COVID-19 pandemic for the community of patients with metabolic disease, obesity and diabetes. This involves the optimal management from surgical obesity programmes to medications and insulin replacement. We also established a global registry analyzing the dimension and role of metabolic disease including new onset diabetes potentially triggered by the virus. We have involved experts of infectious disease and virology to our faculty with this metabolic training programme to offer the full breadth and scope of expertise needed to meet these scientific challenges. We have all learned that this pandemic does not respect or heed any national borders and that we have to work together as a global community. We believe that this transCampus metabolic training programme provides a prime example how an international team of established experts in the field of metabolism can work together with students from all over the world to address a new pandemic.

Alignment sensing for optical cavities using radio-frequency jitter modulation.

Alignment sensing is often required in precision interferometry applications such as Advanced LIGO in order to achieve the optimum performance. Currently favored sensing schemes rely on the use of two separate radio-frequency (RF) quadrant photodetectors and Gouy phase telescopes to determine the alignment of a beam relative to an optical cavity axis. In this paper, we demonstrate an alternative sensing scheme that has potential advantages over the current standard schemes. We show that by using electro-optic beam deflectors to impose RF jitter sidebands on a beam, it is possible to extract full alignment signals for two in-line optical cavities from just one single-element photodetector in reflection of each cavity.

The MCP-4/MCP-1 ratio in plasma is a candidate circadian biomarker for chronic post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is psychiatric disease, which can occur following exposure to traumatic events. PTSD may be acute or chronic, and can have a waxing and waning course of symptoms. It has been hypothesized that proinflammatory cytokines and chemokines in the cerebrospinal fluid (CSF) or plasma might be mediators of the psychophysiological mechanisms relating a history of trauma exposure to changes in behavior and mental health disorders, and medical morbidity. Here we test the cytokine/chemokine hypothesis for PTSD by examining levels of 17 classical cytokines and chemokines in CSF, sampled at 0900 hours, and in plasma sampled hourly for 24 h. The PTSD and healthy control patients are from the NIMH Chronic PTSD and healthy control cohort, initially described by Bonne et al. (2011), in which the PTSD patients have relatively low comorbidity for major depressive disorder (MDD), drug or alcohol use. We find that in plasma, but not CSF, the bivariate MCP4 (CCL13)/ MCP1(CCL2) ratio is ca. twofold elevated in PTSD patients compared with healthy controls. The MCP-4/MCP-1 ratio is invariant over circadian time, and is independent of gender, body mass index or the age at which the trauma was suffered. By contrast, MIP-1ß is a candidate biomarker for PTSD only in females, whereas TARC is a candidate biomarker for PTSD only in males. It remains to be discovered whether these disease-specific differences in circadian expression for these specific immune signaling molecules are biomarkers, surrogates, or drivers for PTSD, or whether any of these analytes could contribute to therapy.

Small optic suspensions for Advanced LIGO input optics and other precision optical experiments.

We report on the design and performance of small optic suspensions developed to suppress seismic motion of out-of-cavity optics in the input optics subsystem of the Advanced Laser Interferometer Gravitational Wave Observatory. These compact single stage suspensions provide isolation in all six degrees of freedom of the optic, local sensing and actuation in three of them, and passive damping for the other three.

Serological, genomic and structural analyses of the major mite allergen Der p 23.

BACKGROUND: Der p 23 was recently identified in a European population as a major allergen and potentially a chitin binding protein. OBJECTIVE: This study sought to assess the importance of Der p 23 among other Dermatophagoides allergens in a North American population and to determine the structure for functional characterization. METHODS: IgE binding to Der p 23, Der p 1, Der p 2, Der p 5, Der p 7 and Der p 8 was measured by ELISA. RNA-seq data from D. pteronyssinus were compared as estimates of allergen expression levels. The structure was analysed by X-ray crystallography and NMR. RESULTS: Despite a high prevalence of Der p 23, (75% vs. 87% and 79% for Der p 1 and Der p 2, respectively), the anti-Der p 23 IgE levels were relatively low. The patient response to the 6 allergens tested was variable (n = 47), but on average anti-Der p 1 and anti-Der p 2 together accounted for 85% of the specific IgE. In terms of abundance, the RNA expression level of Der p 23 is the lowest of the major allergens, thirty fold less than Der p 1 and sevenfold less than Der p 2. The structure of Der p 23 is a small, globular protein stabilized by two disulphide bonds, which is structurally related to allergens such as Blo t 12 that contain carbohydrate binding domains that bind chitin. Functional assays failed to confirm chitin binding by Der p 23. CONCLUSIONS AND CLINICAL RELEVANCE: Der p 23 accounts for a small percentage of the IgE response to mite allergens, which is dominated by Der p 1 and Der p 2. The prevalence and amount of specific IgE to Der p 23 and Der p 2 are disproportionately high compared to the expression of other Dermatophagoides allergens.

Study participation rate of patients with acute spinal cord injury early during rehabilitation.

STUDY DESIGN: Retrospective observational study. OBJECTIVES: To investigate the study participation rate of patients with acute spinal cord injury (SCI) early during rehabilitation after conveying preliminary study information. SETTING: Single SCI rehabilitation center in Switzerland. METHODS: Newly admitted acute SCI patients receive a flyer to inform them concerning the purpose of clinical research, patient rights and active studies. Upon patient request, detailed study information is given. The rate of patients asking for detailed information (study interest) and the rate of study participation was evaluated from May 2013 to October 2014. Furthermore, the number of patients not withdrawing consent to the utilization of coded health-related data was determined. RESULTS: The flyer was given to 144 of the 183 patients admitted during the observation period. A total of 96 patients (67%) were interested in receiving detailed information, and 71 patients (49%) finally participated in at least one study. The vast majority of patients (that is, 91%) did not withdraw consent for retrospective data analysis. An age over 60 years had a significantly (P⩽0.023) negative effect on study interest and participation, and the consent rate to retrospective data analysis was significantly (P<0.04) lower in patients older than 75 years. Study interest and participation were reduced more than 5 and 14-fold, respectively, in patients older than 60 years. CONCLUSIONS: The relatively low (approximately 50%) study participation rates of acute SCI patients should be considered when planning clinical trials. The recruitment of patients older than 60 years may be reduced substantially.

Parallel phase modulation scheme for interferometric gravitational-wave detectors.

Advanced LIGO (aLIGO) requires multiple frequency sidebands to disentangle all of the main interferometer's length signals. This paper presents the results of a risk reduction experiment to produce two sets of frequency sidebands in parallel, avoiding mixed 'sidebands on sidebands'. Two phase modulation frequencies are applied to separate Electro-Optic Modulators (EOMs), with one EOM in each of the two arms of a Mach-Zehnder interferometer. In this system the Mach-Zehnder's arm lengths are stabilized to reduce relative intensity noise in the recombined carrier beam by feeding a corrective control signal back to the Rubidium Titanyl Phosphate (RTP) EOM crystals to drive the optical path length difference to zero. This setup's use of the RTP crystals as length actuators provides enough bandwidth in the feedback to meet arm length stability requirements for aLIGO.

Delivering kidney cancer care in rural Central and Southern Illinois: a telemedicine approach.

There is a growing body of experience and research suggesting that telemedicine (video conferencing, smart phones and online patient portals) could be the solution to addressing gaps in the provision of specialised healthcare in rural areas. The proposed role of telemedicine in providing needed services in hard to reach areas is not new. The United States Telecommunication Act of 1996 provided the initial traction for telemedicine by removing important economic and legal obstacles regarding the use of technology in healthcare delivery. This initial ruling has been supplemented by the availability of federal funding to support efforts aimed at developing telemedicine in underserved areas. In this paper, we explore one aspect of disease disparity pertinent to rural Illinois (kidney cancer incidence and mortality) and describe how we are planning to use an existing telemedicine program at Southern Illinois University School of Medicine (SIUSOM) to improve kidney cancer (Kca) care in rural Illinois. This represents an example of the possible role of telemedicine in addressing healthcare disparities in rural areas/communities and provides a description of general challenges and barriers to the implementation and maintenance of such systems.

Disturbed cingulate glutamate metabolism in adults with high-functioning autism spectrum disorder: evidence in support of the excitatory/inhibitory imbalance hypothesis.

Over the last few years, awareness of autism spectrum disorder (ASD) in adults has increased. The precise etiology of ASD is still unresolved. Animal research, genetic and postmortem studies suggest that the glutamate (Glu) system has an important role, possibly related to a cybernetic imbalance between neuronal excitation and inhibition. To clarify the possible disruption of Glu metabolism in adults with high-functioning autism, we performed a magnetic resonance spectroscopy (MRS) study investigating the anterior cingulate cortex (ACC) and the cerebellum in adults with high-functioning ASD. Twenty-nine adult patients with high-functioning ASD and 29 carefully matched healthy volunteers underwent MRS scanning of the pregenual ACC and the left cerebellar hemisphere. Metabolic data were compared between groups and were correlated with psychometric measures of autistic features. We found a significant decrease in the cingulate N-acetyl-aspartate (NAA) and the combined Glu and glutamine (Glx) signals in adults with ASD, whereas we did not find other metabolic abnormalities in the ACC or the cerebellum. The Glx signal correlated significantly with psychometric measures of autism, particularly with communication deficits. Our data support the hypothesis that there is a link between disturbances of the cingulate NAA and Glx metabolism, and autism. The findings are discussed in the context of the hypothesis of excitatory/inhibitory imbalance in autism. Further research should clarify the specificity and dynamics of these findings regarding other neuropsychiatric disorders and other brain areas.

Pediatric patients with Marfan syndrome: frequency of dural ectasia and its correlation with common cardiovascular manifestations.

PURPOSE: Marfan syndrome (MFS) is a genetic disorder of the connective tissue. Aortic root dilation is a main criterion of the Ghent Nosology. Dural ectasia and the presence of mitral valve prolapse (MVP) contribute to its systemic score. The purpose of this study was to investigate the frequency of dural ectasia and its correlation with cardiovascular manifestations in a pediatric study population. PATIENTS AND METHODS: 119 pediatric patients with confirmed or suspected MFS were examined in the local Marfan Clinic. 31 children with MFS who underwent magnetic resonance imaging (MRI) were included. Each patient was evaluated according to the Ghent nosology. Echocardiography was used to measure the aortic root diameter and assess the presence of MVP and mitral regurgitation. Z-scores were calculated for the evaluation of the aortic root diameters. MRI was performed to determine the dural sac ratio (DSR). RESULTS: The prevalence of dural ectasia was 90.3 %, of aortic root dilation 32.2 %, of MVP 64.5 % and of mitral regurgitation 51.6 %. DSR at L5 correlated with the intraindividual z-scores (slope, 3.62 ±â€Š1.5 [0.56; 6.68]; r = 0.17; p = 0.02; F = 5.84). Z-scores ≥ 2 were accompanied by dural ectasia in 100 %, MVP in 95 % and mitral regurgitation in 100 % of cases. MVP was accompanied by mitral regurgitation in 70 % of cases. CONCLUSION: As the examined cardiac manifestations show a coincidence with dural ectasia in 95 - 100 % of cases, MRI for diagnostic dural sac imaging should be reserved for MFS suspicions with the absence of those manifestations in order to establish the diagnosis according to the Ghent criteria. Thus, the present study supports the recent downgrading of dural ectasia to a contributor to the systemic score.

Identification of Maillard reaction products on peanut allergens that influence binding to the receptor for advanced glycation end products.

BACKGROUND: Recent immunological data demonstrated that dendritic cells preferentially recognize advanced glycation end product (AGE)-modified proteins, upregulate expression of the receptor for AGE (RAGE), and consequently bias the immune response toward allergy. METHODS: Peanut extract was characterized by mass spectrometry (MS) to elucidate the specific residues and specific AGE modifications found in raw and roasted peanuts and on rAra h 1 that was artificially glycated by incubation with glucose or xylose. The binding of the RAGE-V1C1 domain to peanut allergens was assessed by PAGE and Western analysis with anti-Ara h 1, 2, and 3 antibodies. IgE binding to rAra h 1 was also assessed using the same methods. RESULTS: AGE modifications were found on Ara h 1 and Ara h 3 in both raw and roasted peanut extract. No AGE modifications were found on Ara h 2. Mass spectrometry and Western blot analysis demonstrated that RAGE binds selectively to Ara h 1 and Ara h 3 derived from peanut extract, whereas the analysis failed to demonstrate Ara h 2 binding to RAGE. rAra h 1 with no AGE modifications did not bind RAGE; however, after AGE modification with xylose, rAra h 1 bound to RAGE. CONCLUSIONS: AGE modifications to Ara h 1 and Ara h 3 can be found in both raw and roasted peanuts. Receptor for AGE was demonstrated to selectively interact with AGE-modified rAra h 1. If sensitization to peanut allergens occurs in dendritic cells via RAGE interactions, these cells are likely interacting with modified Ara h 1 and Ara h 3, but not Ara h 2.

Improvement of renal graft function after conversion from a calcineurin inhibitor including immunosuppression to a mycophenolate sodium including regimen: a 4-year follow-up.

BACKGROUND: The most common immunosuppressive regimens after renal transplantation include calcineurin inhibitors (CNI). However, due to renal toxicity long-term graft survival does not seem to be positively affected by CNIs. METHODS: In the present study, we investigated 17 patients, in which the CNI immunosuppression was converted to a CNI-free, mycophenolate sodium (MPS) regimen. Conversion was performed due to progressive impairment of the graft function from suspected CNI toxicity. We retrospectively analyzed graft function as well as toxicity and surrogate markers for 4 years before and 4 years after conversion using a repeated-measures mixed model data analysis and/or a paired sample t-test. RESULTS: The mean time point of therapy conversion was 11.2 ± 4.6 years after transplantation. Within 1 month of CNI discontinuation, allograft function improved significantly, remaining at a significant level for 2 years. The estimated glomerular filtration rate increased from 43.4 ± 14.8 to a maximum of 55.7 ± 21.7 mL/min at 1 year after conversion (P = .0027). After 4 years, the end of the observation period, renal function was similar to the baseline. There were no significant side effects. CONCLUSION: These data suggested that, when chronic CNI-toxicity is suspected, renal allograft recipients may benefit from CNI withdrawal in favor of a MPS-including immunosuppressive regimen.

Cardiac characterization of 16 patients with large NF1 gene deletions.

The aim of this study was to characterize cardiac features of patients with neurofibromatosis 1 (NF1) and large deletions of the NF1 gene region. The study participants were 16 patients with large NF1 deletions and 16 age- and sex-matched NF1 patients without such deletions. All the patients were comprehensively characterized clinically and by echocardiography. Six of 16 NF1 deletion patients but none of 16 non-deletion NF1 patients have major cardiac abnormalities (p = 0.041). Congenital heart defects (CHDs) include mitral insufficiency in two patients and ventricular septal defect, aortic stenosis, and aortic insufficiency in one patient each. Three deletion patients have hypertrophic cardiomyopathy. Two patients have intracardiac tumors. NF1 patients without large deletions have increased left ventricular (LV) diastolic posterior wall thickness (p < 0.001) and increased intraventricular diastolic septal thickness (p = 0.001) compared with a healthy reference population without NF1, suggestive of eccentric LV hypertrophy. CHDs and other cardiovascular anomalies are more frequent among patients with large NF1 deletion and may cause serious clinical complications. Eccentric LV hypertrophy may occur in NF1 patients without whole gene deletions, but the clinical significance of this finding is uncertain. All patients with clinical suspicion for NF1 should be referred to a cardiologist for evaluation and surveillance.

The impact of regional deprivation and individual socio-economic status on the prevalence of Type 2 diabetes in Germany. A pooled analysis of five population-based studies.

AIM: Our objective was to test the hypothesis that the prevalence of Type 2 diabetes increases with increasing regional deprivation even after controlling for individual socio-economic status. METHODS: We pooled cross-sectional data from five German population-based studies. The data set contained information on n = 11,688 study participants (men 50.1%) aged 45-74 years, of whom 1008 people had prevalent Type 2 diabetes (men 56.2%). Logistic multilevel regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI) for diabetes prevalence. We controlled for sex, age and lifestyle risk factors, individual socio-economic status and regional deprivation, based on a new small-area deprivation measure, the German Index of Multiple Deprivation. RESULTS: Adjusted for sex, age, body mass index (BMI), physical activity, smoking status and alcohol consumption, the prevalence of Type 2 diabetes showed a stepwise increase in risk with increasing area deprivation [OR 1.88 (95% CI 1.16-3.04) in quintile 4 and OR 2.14 (95% CI 1.29-3.55) in quintile 5 compared with the least deprived quintile 1], even after controlling for individual socio-economic status. Focusing on individual socio-economic status alone, the risk of having diabetes was significantly higher for low compared with medium or high educational level [OR 1.46 (95% CI 1.24-1.71)] and for the lowest compared with the highest income group [OR 1.53 (95% CI 1.18-1.99)]. CONCLUSION: Regional deprivation plays a significant part in the explanation of diabetes prevalence in Germany independently of individual socio-economic status. The results of the present study could help to target public health measures in deprived regions.

Note: silicon carbide telescope dimensional stability for space-based gravitational wave detectors.

Space-based gravitational wave detectors are conceived to detect gravitational waves in the low frequency range by measuring the distance between proof masses in spacecraft separated by millions of kilometers. One of the key elements is the telescope which has to have a dimensional stability better than 1 pm Hz(-1/2) at 3 mHz. In addition, the telescope structure must be light, strong, and stiff. For this reason a potential telescope structure consisting of a silicon carbide quadpod has been designed, constructed, and tested. We present dimensional stability results meeting the requirements at room temperature. Results at -60 °C are also shown although the requirements are not met due to temperature fluctuations in the setup.