Pain coping skills training un-locks patient-centered pain care during the COVID- 19 lockdown.

BACKGROUND: In 2020, the COVID-19 virus sparked a crisis constituting a nationwide public health emergency that rapidly altered the provision of healthcare services for all Americans. Infectious disease mitigation led to widespread lockdowns of perceived nonessential services, programs, and non-emergent healthcare interventions. This lockdown exacerbated the public health dyad of uncontrolled pain and the opioid epidemic, which was already in a crisis state. Current literature supports the management of uncontrolled pain with a biopsychosocial approach, empowering patients to explore self-care to enhance activities of daily living. Pain Coping Skills Training (PCST) delivers real-life strategies that improve quality of life and strengthen self-efficacy. Self-efficacy has been identified as a patient outcome measure that demonstrates improved patient-perceived function and quality of life despite pain intensity. Studies have shown that nurse practitioners (APRN) are well-positioned to provide PCST to chronic pain sufferers. METHODS: A pretest-posttest design was utilized for this project to enhance pain self- efficacy through an APRN-led community-based intervention. INTERVENTION: Community-dwelling adults treated in a specialty pain management practice were self-selected to participate in a 6-week telehealth delivered PCST Program. This APRN delivered program presented basic pain education and a broad range of evidence-based nonpharmacologic pain management self-care tools. The primary outcome was improved Pain Self-efficacy measured with the pain self-efficacy questionnaire (PSEQ), with secondary outcomes of improved perceived pain intensity and function measured with the pain, enjoyment, and general activity (PEG) scale tracked weekly. RESULTS: Baseline PSEQ and weekly PEG scores were obtained and compared to scores after the program. Collateral data points included confidence in using complementary and alternative nonpharmacologic interventions, satisfaction with the program, and a qualitative patient statement regarding pre-and post-intervention participation. CONCLUSIONS: This project concluded that a Nurse Practitioner delivered PCST program via telehealth technology could provide community-dwelling adults with an intervention that improves pain self-efficacy, enhances self-reported PEG measures, and meets the social distancing requirements that continue to impact patients during the COVID-19 pandemic.

Neutrally charged self-assembling peptide hydrogel recapitulates in vitro mechanisms of breast cancer progression.

Self-assembling peptide hydrogels (SAPH) are a popular biomaterial due to their biocompatibility with a wide range of cell types, synthetic design, structural properties that provide a more accurate 3D microenvironment, and potential for cell- and/or drug-delivery system. Mimicking solid tumors in vitro using hydrogels is one method of testing anti-cancer drug efficacy and observing cancerous cell-ECM interactions within a 3D system. In this study, a SAPH, PeptiGel®Alpha1, was used to model in vitro the 3D breast tumor microenvironment. PeptiGel®Alpha1 is composed of entangled nanofibers with consistent diameter and mechanical properties similar to breast cancer that more accurately mimic the stiffness of breast tumor tissue than Matrigel® or collagen type I. PeptiGel®Alpha1 supported the viability and growth of the breast cancer cell lines MCF-7 and MDA-MB-231 and recapitulated key features of solid tumors such as hypoxia and invasion. MCF-7 cells in the hydrogels formed large spheroids resembling acini, while MDA-MB-231 remained dispersed. When treated with tamoxifen, PeptiGel®Alpha1 acted as a barrier, providing drug penetration geometry similar to that in vivo, providing better prediction of the drug effect. Finally, it was observed that MCF-7 cells engulfed the peptide matrix after 14 days, highlighting a potential use in drug delivery. PeptiGel®Alpha1 is a suitable platform for in vitro modeling of breast cancer.

Expanding access to nurse-managed medication for opioid use disorder.

BACKGROUND: Advanced practice registered nurses (APRNs) are increasingly caring for individuals with opioid use disorder. Advances have been made to increase APRN education, outreach, and prescribing privileges, but as demand for medication for opioid use disorder (MOUD) grows, evidence suggests that policy and care barriers inhibit the ability of APRNs to support MOUD. PURPOSE: This paper highlights the significant challenges of expanding access to buprenorphine prescribing by APRNs. FINDINGS: Barriers and recommendations were derived from the culmination of literature review, expert consensus discussions among a diverse stakeholder panel including patient representatives, and feedback from community webinars with care providers. DISCUSSION: We provide an overview of existing care barriers, promising practices, and proposed recommendations to enhance the care of individuals and communities with opioid use disorder.

TGF-ß3-loaded graphene oxide - self-assembling peptide hybrid hydrogels as functional 3D scaffolds for the regeneration of the nucleus pulposus.

Intervertebral disc (IVD) degeneration is a process that starts in the central nucleus pulposus (NP) and leads to inflammation, extracellular matrix (ECM) degradation, and progressive loss of disc height. Early treatment of IVD degeneration is critical to the reduction of low back pain and related disability. As such, minimally invasive therapeutic approaches that can halt and reverse NP degeneration at the early stages of the disease are needed. Recently, we developed an injectable graphene oxide (GO) - self-assembling peptide FEFKFEFK (F: phenylalanine; K: lysine; E: glutamic acid) hybrid hydrogels as potential delivery platform for cells and/or drugs in the NP. In this current study, we explored the possibility of using the GO present in these hybrid hydrogels as a vehicle for the sequestration and controlled delivery of transforming growth factor beta-3 (TGF-ß3), an anabolic growth factor (GF) known to direct NP cell fate and function. For this purpose, we first investigated the potential of GO to bind and sequestrate TGF-ß3. We then cultured bovine NP cells in the new functional scaffolds and investigated their response to the presence of GO and TGF-ß3. Our results clearly showed that GO flakes can sequestrate TGF-ß3 through strong binding interactions resulting in a slow and prolonged release, with the GF remaining active even when bound to the GO flakes. The adsorption of the GF on the GO flakes to create TGF-ß3-loaded GO flakes and their subsequent incorporation in the hydrogels through mixing, [(GO/TGF-ß3Ads)-F8] hydrogel, led to the upregulation of NP-specific genes, accompanied by the production and deposition of an NP-like ECM, rich in aggrecan and collagen II. NP cells actively interacted with TGF-ß3-loaded GO flakes and remodeled the scaffolds through endocytosis. This work highlights the potential of using GO as a nanocarrier for the design of functional hybrid peptide-based hydrogels. STATEMENT OF SIGNIFICANCE: Intervertebral disc (IVD) degeneration is a process that starts in the central nucleus pulposus (NP) and leads to inflammation, extracellular matrix (ECM) degradation, and progressive loss of disc height. As such, minimally invasive therapeutic approaches that can halt and reverse NP degeneration at the early stages of the disease are needed. In this current study, we explored the possibility of using peptide - GO hybrid hydrogels as a vehicle for the sequestration and controlled delivery of transforming growth factor beta-3 (TGF-ß3), an anabolic growth factor (GF) known to direct NP cell fate and function.

Engineering a cell-hydrogel-fibre composite to mimic the structure and function of the tendon synovial sheath.

The repair of tendon injuries is often compromised by post-operative peritendinous adhesions. Placing a physical barrier at the interface between the tendon and the surrounding tissue could potentially solve this problem by reducing adhesion formation. At present, no such system is available for routine use in clinical practice. Here, we propose the development of a bilayer membrane combining a nanofibrous poly(ε-caprolactone) (PCL) electrospun mesh with a layer of self-assembling peptide hydrogel (SAPH) laden with type-B synoviocytes. This bilayer membrane would act as an anti-adhesion system capable of restoring tendon lubrication, while assisting with synovial sheath regeneration. The PCL mesh showed adequate mechanical properties (Young's modulus=19±4 MPa, ultimate tensile stress=9.6±1.7 MPa, failure load=0.5±0.1 N), indicating that the membrane is easy to handle and capable to withstand the frictional forces generated on the tendon's surface during movement (~0.3 N). Morphological analysis confirmed the generation of a mesh with nanosized PCL fibres and small pores (< 3 µm), which prevented fibroblast infiltration to impede extrinsic healing but still allowing diffusion of nutrients and waste. Rheological tests showed that incorporation of SAPH layer allows good lubrication properties when the membrane is articulated against porcine tendon or hypodermis, suggesting that restoration of tendon gliding is possible upon implantation. Moreover, viability and metabolic activity tests indicated that the SAPH was conducive to rabbit synoviocyte growth and proliferation over 28 days of 3D culture, sustaining cell production of specific matrix components, particularly hyaluronic acid. Synoviocyte-laden peptide hydrogel promoted a sustained endogenous production of hyaluronic acid, providing an anti-friction layer that potentially restores the tendon gliding environment.

Barrett's Registry Collaboration of academic centers in Ireland reveals high progression rate of low-grade dysplasia and low risk from nondysplastic Barrett's esophagus: report of the RIBBON network.

Barrett's esophagus (BE) is the main pathological precursor of esophageal adenocarcinoma (EAC). Progression to high-grade dysplasia (HGD) or EAC from nondysplastic BE (NDBE), low-grade dysplasia (LGD) and indefinite for dysplasia (IND) varies widely between population-based studies and specialized centers for many reasons, principally the rigor of the biopsy protocol and the accuracy of pathologic definition. In the Republic of Ireland, a multicenter prospective registry and bioresource (RIBBON) was established in 2011 involving six academic medical centers, and this paper represents the first report from this network. A detailed clinical, endoscopic and pathologic database registered 3,557 patients. BE was defined strictly by both endoscopic evidence of Barrett's epithelium and the presence of specialized intestinal metaplasia (SIM). A prospective web-based database was used to gather information with initial and follow-up data abstracted by a data manager at each site. A total of 2,244 patients, 1,925 with no dysplasia, were included with complete follow-up. The median age at diagnosis was 60.5 with a 2.1:1 male to female ratio and a median follow-up time of 2.7 years (IQR 1.19-4.04), and 6609.25 person years. In this time period, 125 (5.57%) progressed to HGD/EAC, with 74 (3.3%) after 1 year of follow-up and 38 (1.69%) developed EAC, with 20 (0.89%) beyond 1 year. The overall incidence of HGD/EAC was 1.89% per year; 1.16% if the first year is excluded. The risk of progression to EAC alone overall was 0.57% per year, 0.31% excluding the first year, and 0.21% in the 1,925 patients who had SIM alone at diagnosis. Low-grade dysplasia (LGD) progressed to HGD/EAC in 31% of patients, a progression rate of 12.96% per year, 6.71% with the first year excluded. In a national collaboration of academic centers in Ireland, the progression rate for NDBE was similar to recent population studies. Almost one in two who progressed was evident within 1 year. Crucially, LGD diagnosed and confirmed by specialist gastrointestinal pathologists represents truly high-risk disease, highlighting the importance of expertise in diagnosis and management, and providing indirect support for ablative therapies in this context.

Anisotropic crack propagation and deformation in dentin observed by four-dimensional X-ray nano-computed tomography.

Understanding the cracking behaviour of biological composite materials is of practical importance. This paper presents the first study to track the interplay between crack initiation, microfracture and plastic deformation in three dimensions (3D) as a function of tubule and collagen fibril arrangement in elephant dentin using in situ X-ray nano-computed tomography (nano-CT). A nano-indenter with a conical tip has been used to incrementally indent three test-pieces oriented at 0°, 45° and 70° to the long axis of the tubules (i.e. radial to the tusk). For the 0° sample two significant cracks formed, one of which linked up with microcracks in the axial-radial plane of the tusk originating from the tubules and the other one occurred as a consequence of shear deformation at the tubules. The 70° test-piece was able to bear the greatest loads despite many small cracks forming around the indenter. These were diverted by the microstructure and did not propagate significantly. The 45° test-piece showed intermediate behaviour. In all cases strains obtained by digital volume correlation were well in excess of the yield strain (0.9%), indeed some plastic deformation could even be seen through bending of the tubules. The hoop strains around the conical indenter were anisotropic with the smallest strains correlating with the primary collagen orientation (axial to the tusk) and the largest strains aligned with the hoop direction of the tusk. STATEMENT OF SIGNIFICANCE: This paper presents the first comprehensive study of the anisotropic nature of microfracture, crack propagation and deformation in elephant dentin using time-lapse X-ray nano-computed tomography. To unravel the interplay of collagen fibrils and local deformation, digital volume correlation (DVC) has been applied to map the local strain field while the crack initiation and propagation is tracked in real time. Our results highlight the intrinsic and extrinsic shielding mechanisms and correlate the crack growth behavior in nature to the service requirement of dentin to resist catastrophic fracture. This is of wide interest not just in terms of understanding dentin fracture but also can extend beyond dentin to other anisotropic structural composite biomaterials such as bone, antler and chitin.

Four-Dimensional Imaging of Soft Tissue and Implanted Biomaterial Mechanics: A Barbed Suture Case Study for Tendon Repair.

Timely, recent developments in X-ray microcomputed tomography (XµCT) imaging such as increased resolution and improved sample preparation enable nondestructive time-lapse imaging of polymeric biomaterials when implanted in soft tissue, which we demonstrate herein. Imaging the full three-dimensional (3D) structure of an implanted biomaterial provides new opportunities to assess the micromechanics of the interface between the implant and tissues and how this changes over time as force is applied in load-bearing musculoskeletal applications. In this paper, we present a case study demonstrating in situ XµCT and finite element analysis, using a dynamically loaded barbed suture repair for its novel use in tendon tissue. The aim of this study was to identify the distribution of stress in the suture and tendon as load is applied. The data gained demonstrate a clear 3D visualization of microscale features in both the tissue and implant in wet conditions. XµCT imaging has revealed, for the first time, pores around the suture, preventing full engagement of all the barbs with the tendon tissue. Subsequent finite element analysis reveals the localized stress and strain, which are not evenly distributed along the suture, or throughout the tissue. This case study demonstrates for the first time a powerful in situ mechanical imaging tool, which could be readily adapted by other laboratories to interrogate and optimize the interface between the implanted biomaterials and the soft tissue.

Machine Learning EEG to Predict Cognitive Functioning and Processing Speed Over a 2-Year Period in Multiple Sclerosis Patients and Controls.

Event-related potentials (ERPs) show promise to be objective indicators of cognitive functioning. The aim of the study was to examine if ERPs recorded during an oddball task would predict cognitive functioning and information processing speed in Multiple Sclerosis (MS) patients and controls at the individual level. Seventy-eight participants (35 MS patients, 43 healthy age-matched controls) completed visual and auditory 2- and 3-stimulus oddball tasks with 128-channel EEG, and a neuropsychological battery, at baseline (month 0) and at Months 13 and 26. ERPs from 0 to 700 ms and across the whole scalp were transformed into 1728 individual spatio-temporal datapoints per participant. A machine learning method that included penalized linear regression used the entire spatio-temporal ERP to predict composite scores of both cognitive functioning and processing speed at baseline (month 0), and months 13 and 26. The results showed ERPs during the visual oddball tasks could predict cognitive functioning and information processing speed at baseline and a year later in a sample of MS patients and healthy controls. In contrast, ERPs during auditory tasks were not predictive of cognitive performance. These objective neurophysiological indicators of cognitive functioning and processing speed, and machine learning methods that can interrogate high-dimensional data, show promise in outcome prediction.

Biotransformation of Silver Released from Nanoparticle Coated Titanium Implants Revealed in Regenerating Bone.

Antimicrobial silver nanoparticle coatings have attracted interest for reducing prosthetic joint infection. However, few studies report in vivo investigations of the biotransformation of silver nanoparticles within the regenerating tissue and its impact on bone formation. We present a longitudinal investigation of the osseointegration of silver nanoparticle-coated additive manufactured titanium implants in rat tibial defects. Correlative imaging at different time points using nanoscale secondary ion mass spectrometry, transmission electron microscopy (TEM), histomorphometry, and 3D X-ray microcomputed tomography provided quantitative insight from the nano- to macroscales. The quality and quantity of newly formed bone is comparable between the uncoated and silver coated implants. The newly formed bone demonstrates a trabecular morphology with bone being located at the implant surface, and at a distance, at two weeks. Nanoscale elemental mapping of the bone-implant interface showed that silver was present primarily in the osseous tissue and colocalized with sulfur. TEM revealed silver sulfide nanoparticles in the newly regenerated bone, presenting strong evidence that the previously in vitro observed biotransformation of silver to silver sulfide occurs in vivo.

Cell response to sterilized electrospun poly(ɛ-caprolactone) scaffolds to aid tendon regeneration in vivo.

The functional replacement of tendon represents an unmet clinical need in situations of tendon rupture, tendon grafting, and complex tendon reconstruction, as usually there is a finite source of healthy tendon to use as donors. The microfibrous architecture of tendon is critical to the function of tendon. This study investigates the use of electrospun poly(ɛ-caprolactone) scaffolds as potential biomaterial substitutes for tendon grafts. We assessed the performance of two electrospinning manufacturers (small- and large-scale) and the effect of two sterilization techniques-gamma irradiation and ethanol submersion-on cell response to these electrospun scaffolds after their implantation into a murine tendon model. Cell infiltration and proliferation analyses were undertaken to determine the effect on cell response within the implant over a 6-week period. Immunohistochemical analysis was performed to characterize inflammatory response and healing characteristics (proliferation, collagen deposition, myofibroblast activity, and apoptosis). Neither the sterilization techniques nor the manufacturer was observed to significantly affect the cell response to the scaffold. At each time point, cell response was similar to the autograft control. This suggests that ethanol submersion can be used for research purposes and that the scaffold can be easily reproduced by a large-scale manufacturer. These results further imply that this electrospun scaffold may provide an alternative to autograft, thus eliminating the need for sourcing healthy tendon tissue from a secondary site. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 389-397, 2017.

In vitro evaluation of poly (lactic-co-glycolic acid)/polyisoprene fibers for soft tissue engineering.

The polymeric blend of poly (lactic-co-glycolic acid) (PLGA) and polyisoprene (PI) has recently been explored for application as stents for tracheal stenosis and spring for the treatment of craniosynostosis. From the positive results presented in other biomedical applications comes the possibility of investigating the application of this material as scaffold for tissue engineering (TE), acquiring a deeper knowledge about the polymeric blend by exploring a new processing technique while attending to the most fundamental demands of TE scaffolds. PLGA/PI was processed into randomly oriented microfibers through the dripping technique and submitted to physical-chemical and in vitro characterization. The production process of fibers did not show an effect over the polymer's chemical composition, despite the fact that PLGA and PI were observed to be immiscible. Mechanical assays reinforce the suitability of these scaffolds for soft tissue applications. Skeletal muscle cells demonstrated increases in metabolic activity and proliferation to the same levels of the control group. Human dermal fibroblasts didn't show the same behaviour, but presented cell growth with the same development profile as presented in the control group. It is plausible to believe that PLGA/PI fibrous three-dimensional scaffolds are suitable for applications in soft tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2581-2591, 2017.

Delayed P100-Like Latencies in Multiple Sclerosis: A Preliminary Investigation Using Visual Evoked Spread Spectrum Analysis.

Conduction along the optic nerve is often slowed in multiple sclerosis (MS). This is typically assessed by measuring the latency of the P100 component of the Visual Evoked Potential (VEP) using electroencephalography. The Visual Evoked Spread Spectrum Analysis (VESPA) method, which involves modulating the contrast of a continuous visual stimulus over time, can produce a visually evoked response analogous to the P100 but with a higher signal-to-noise ratio and potentially higher sensitivity to individual differences in comparison to the VEP. The main objective of the study was to conduct a preliminary investigation into the utility of the VESPA method for probing and monitoring visual dysfunction in multiple sclerosis. The latencies and amplitudes of the P100-like VESPA component were compared between healthy controls and multiple sclerosis patients, and multiple sclerosis subgroups. The P100-like VESPA component activations were examined at baseline and over a 3-year period. The study included 43 multiple sclerosis patients (23 relapsing-remitting MS, 20 secondary-progressive MS) and 42 healthy controls who completed the VESPA at baseline. The follow-up sessions were conducted 12 months after baseline with 24 MS patients (15 relapsing-remitting MS, 9 secondary-progressive MS) and 23 controls, and again at 24 months post-baseline with 19 MS patients (13 relapsing-remitting MS, 6 secondary-progressive MS) and 14 controls. The results showed P100-like VESPA latencies to be delayed in multiple sclerosis compared to healthy controls over the 24-month period. Secondary-progressive MS patients had most pronounced delay in P100-like VESPA latency relative to relapsing-remitting MS and controls. There were no longitudinal P100-like VESPA response differences. These findings suggest that the VESPA method is a reproducible electrophysiological method that may have potential utility in the assessment of visual dysfunction in multiple sclerosis.

Symptom overlap in anxiety and multiple sclerosis.

BACKGROUND: The validity of self-rated anxiety inventories in people with multiple sclerosis (pwMS) is unclear. However, the appropriateness of self-reported depression scales has been widely examined. Given somatic symptom overlap between depression and MS, research emphasises caution when using such scales. OBJECTIVE: This study evaluates symptom overlap between anxiety and MS in a group of 33 individuals with MS, using the Beck Anxiety Inventory (BAI). METHODS: Participants underwent a neurological examination and completed the BAI. RESULTS: A novel procedure using hierarchical cluster analysis revealed three distinct symptom clusters. Cluster one ('wobbliness' and 'unsteady') grouped separately from all other BAI items. These symptoms are well-recognised MS-related symptoms and we question whether their endorsement in pwMS can be considered to reflect anxiety. A modified 19-item BAI (mBAI) was created which excludes cluster one items. This removal reduced the number of MS participants considered 'anxious' by 21.21% (low threshold) and altered the level of anxiety severity for a further 27.27%. CONCLUSION: Based on these data, it is suggested that, as with depression measures, researchers and clinicians should exercise caution when using brief screening measures for anxiety in pwMS.

A comparison of the content of memory rehabilitation groups for patients with neurological disabilities.

The aim of the study was to compare the fidelity of manualised group memory rehabilitation programmes for participants with neurological disabilities. A sample of 11 neurological patients with memory problems, enrolled in a randomised controlled trial comparing compensation, restitution and self-help treatments, were observed during group sessions. Time-sampling was used to record the activity of the participants and the content of the discussion at one minute intervals. There was a significant difference between groups in the amount of time the group leader and participants spent talking (p < .001). Participants in the compensation and restitution groups spent significantly more time in memory rehabilitation discussion than participants in the self-help group (p < .001). There was also a significant difference between the amount of time spent discussing internal and external memory aids in the compensation and restitution groups (p < .001). These results support the fidelity of the interventions provided. This study also highlights the usefulness of time-sampling as a method to record the content and activity in rehabilitation groups.

Using a mixed methods research design to investigate complementary alternative medicine (CAM) use among women with breast cancer in Ireland.

AIM: To investigate complementary and alternative medicine (CAM) use among women with breast cancer in Ireland using a mixed methods modified sequential explanatory design. METHODS: Semi-structured interviews were conducted with oncology professionals (n = 20) and CAM practitioners (n = 20) and this was followed by a survey of 406 women with breast cancer using the 'Use of Complementary and Alternative Therapies Survey' questionnaire (UCATS) (Lengacher et al., 2003). Follow up interviews were subsequently undertaken with a subset of this survey sample (n = 31). RESULTS: Over half of those surveyed (55.7%, n = 226) used some form of CAM since diagnosis. The most frequently used therapies were massage, herbal supplements (including herbs with oestrogenic properties), antioxidants, relaxation, counselling, health supplements, reflexology, reiki and support groups. Dietary interventions were used primarily to reduce symptoms and/or side effects while reduction of psychological stress was the primary reason for use of stress-reducing therapies. Most respondents reported that the CAM therapies they had used were helpful. The qualitative data elaborated on and provided clarification of the survey results. CONCLUSIONS: Similar to international studies, CAM is popular among women with breast cancer in Ireland. As such, the challenge for Irish oncology professionals is to identify low risk CAM therapies that are likely to benefit patients while educating patients and themselves on therapies which may be of concern. This study clearly illustrates the benefits of using a mixed methods approach to enhance our understanding of a complex clinical issue and thus we recommend that this method should be the method of choice when planning health services research.

Only low frequency event-related EEG activity is compromised in multiple sclerosis: insights from an independent component clustering analysis.

Cognitive impairment (CI), often examined with neuropsychological tests such as the Paced Auditory Serial Addition Test (PASAT), affects approximately 65% of multiple sclerosis (MS) patients. The P3b event-related potential (ERP), evoked when an infrequent target stimulus is presented, indexes cognitive function and is typically compared across subjects' scalp electroencephalography (EEG) data. However, the clustering of independent components (ICs) is superior to scalp-based EEG methods because it can accommodate the spatiotemporal overlap inherent in scalp EEG data. Event-related spectral perturbations (ERSPs; event-related mean power spectral changes) and inter-trial coherence (ITCs; event-related consistency of spectral phase) reveal a more comprehensive overview of EEG activity. Ninety-five subjects (56 MS patients, 39 controls) completed visual and auditory two-stimulus P3b event-related potential tasks and the PASAT. MS patients were also divided into CI and non-CI groups (n = 18 in each) based on PASAT scores. Data were recorded from 128-scalp EEG channels and 4 IC clusters in the visual, and 5 IC clusters in the auditory, modality were identified. In general, MS patients had significantly reduced ERSP theta power versus controls, and a similar pattern was observed for CI vs. non-CI MS patients. The ITC measures were also significantly different in the theta band for some clusters. The finding that MS patients had reduced P3b task-related theta power in both modalities is a reflection of compromised connectivity, likely due to demyelination, that may have disrupted early processes essential to P3b generation, such as orientating and signal detection. However, for posterior sources, MS patients had a greater decrease in alpha power, normally associated with enhanced cognitive function, which may reflect a compensatory mechanism in response to the compromised early cognitive processing.

Scleroderma renal crisis-like acute renal failure associated with mucopolysaccharide accumulation in renal vessels in a patient with scleromyxedema.

Scleromyxedema is a systemic disease characterized by lichenoid papules, nodules, and plaques on the skin and often diffuse skin induration resembling the cutaneous involvement of systemic sclerosis. The systemic involvement affects the musculoskeletal, pulmonary, cardiovascular, gastrointestinal, and central nervous systems, and the disorder is commonly associated with a paraproteinemia. Involvement of the kidney is rare and not considered a feature of the disease. Here, we describe an unusual case of scleromyxedema complicated by the development of scleroderma renal crisis-like acute renal failure with a marked intimal deposition of mucin, mucopolysaccharides, and hyaluronic acid in the intrarenal vessels.

Gastric antral vascular ectasia in systemic sclerosis: demographics and disease predictors.

OBJECTIVES: To evaluate patients with systemic sclerosis (SSc) who have gastric antral vascular ectasia (GAVE), to further characterize this disease association, and to identify factors that may predict which patients with SSc are at greatest risk for the development of GAVE. METHODS: Patients with a diagnosis of both SSc and GAVE were identified from the Division of Rheumatology at Georgetown University and Thomas Jefferson University. A chart review was conducted to obtain the demographic data. RESULTS: Twenty-eight patients were included in this analysis, including 17 with diffuse cutaneous (dcSSc) and 11 with limited cutaneous SSc (lcSSc). The mean disease duration at diagnosis with GAVE was 21.5 months for dcSSc and 84.3 months for lcSSc (p = 0.025). Seventy-six percent of patients with dcSSc developed GAVE within 18 months of first scleroderma symptom onset. Over half of patients with early GAVE also had rapidly progressive cutaneous disease. Only 4% had antitopoisomerase I antibody. Although only 1 patient was tested and had positive RNA polymerase (RNAP) III, RNAP III may be overrepresented in this GAVE population. Mean hematocrit levels were 23.8% in dcSSc and 29% in lcSSc. CONCLUSION: dcSSc is associated with earlier development of GAVE, as well as more severe anemia requiring more therapeutic interventions. Rapid progression of cutaneous disease may suggest earlier development of GAVE. Absence of antitopoisomerase I antibodies and presence of antibodies to RNAP III/speckled antinuclear antibody pattern may be useful to identify the subset of patients with SSc with increased risk for GAVE.

Improvement of severe systemic sclerosis-associated gastric antral vascular ectasia following immunosuppressive treatment with intravenous cyclophosphamide.

OBJECTIVE: We describe 3 patients with systemic sclerosis (SSc) with severe, transfusion-dependent gastric antral vascular ectasia (GAVE) refractory to laser ablation who showed remarkable clinical and endoscopic improvement following intravenous (IV) pulse cyclophosphamide (CYC) treatment. METHODS: Review of clinical records and upper gastrointestinal endoscopy images from 3 patients with SSc and severe GAVE before and after treatment with IV pulse CYC. RESULTS: IV CYC was followed by improvement and stabilization of hemoglobin levels, and marked reduction in blood transfusion requirements and the number and frequency of endoscopic laser treatments. CONCLUSION: IV pulse CYC immunosuppression was followed by remarkable clinical and endoscopic improvement of SSc-associated GAVE.