An Update on Emerging Regenerative Medicine Applications: The Use of Extracellular Vesicles and Exosomes for the Management of Chronic Pain.

PURPOSE OF REVIEW: Chronic pain affects nearly two billion people worldwide, surpassing heart disease, diabetes, and cancer in terms of economic costs. Lower back pain alone is the leading cause of years lived with disability worldwide. Despite limited treatment options, regenerative medicine, particularly extracellular vesicles (EVs) and exosomes, holds early promise for patients who have exhausted other treatment options. EVs, including exosomes, are nano-sized structures released by cells, facilitating cellular communication through bioactive molecule transfer, and offering potential regenerative properties to damaged tissues. Here, we review the potential of EVs and exosomes for the management of chronic pain. RECENT FINDINGS: In osteoarthritis, various exosomes, such as those derived from synovial mesenchymal stem cells, human placental cells, dental pulp stem cells, and bone marrow-derived mesenchymal stem cells (MSCs), demonstrate the ability to reduce inflammation, promote tissue repair, and alleviate pain in animal models. In intervertebral disc disease, Wharton's jelly MSC-derived EVs enhance cell viability and reduce inflammation. In addition, various forms of exosomes have been shown to reduce signs of inflammation in neurons and alleviate pain in neuropathic conditions in animal models. Although clinical applications of EVs and exosomes are still in the early clinical stages, they offer immense potential in the future management of chronic pain conditions. Clinical trials are ongoing to explore their therapeutic potential further, and with more research the potential applicability of EVs and exosomes will be fully understood.

Sensitivity of the SCI-FI/AT in Individuals With Traumatic Spinal Cord Injury.

OBJECTIVE: To examine the ability of the Spinal Cord Injury-Functional Index/Assistive Technology (SCI-FI/AT) measure to detect change in persons with spinal cord injury (SCI). DESIGN: Multisite longitudinal (12-mo follow-up) study. SETTING: Nine SCI Model Systems programs. PARTICIPANTS: Adults (N=165) with SCI enrolled in the SCI Model Systems database. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: SCI-FI/AT computerized adaptive test (CAT) (Basic Mobility, Self-Care, Fine Motor Function, Wheelchair Mobility, and/or Ambulation domains) completed at discharge from rehabilitation and 12 months after SCI. For each domain, effect size estimates and 95% confidence intervals were calculated for subgroups with paraplegia and tetraplegia. RESULTS: The demographic characteristics of the sample were as follows: 46% (n=76) individuals with paraplegia, 76% (n=125) male participants, 57% (n=94) used a manual wheelchair, 38% (n=63) used a power wheelchair, 30% (n=50) were ambulatory. For individuals with paraplegia, the Basic Mobility, Self-Care, and Ambulation domains of the SCI-FI/AT detected a significantly large amount of change; in contrast, the Fine Motor Function and Wheelchair Mobility domains detected only a small amount of change. For those with tetraplegia, the Basic Mobility, Fine Motor Function, and Self-Care domains detected a small amount of change whereas the Ambulation item domain detected a medium amount of change. The Wheelchair Mobility domain for people with tetraplegia was the only SCI-FI/AT domain that did not detect significant change. CONCLUSIONS: SCI-FI/AT CAT item banks detected an increase in function from discharge to 12 months after SCI. The effect size estimates for the SCI-FI/AT CAT vary by domain and level of lesion. Findings support the use of the SCI-FI/AT CAT in the population with SCI and highlight the importance of multidimensional functional measures.

Randomized Trial of a Peer-Led, Telephone-Based Empowerment Intervention for Persons With Chronic Spinal Cord Injury Improves Health Self-Management.

OBJECTIVE: To evaluate the impact of "My Care My Call" (MCMC), a peer-led, telephone-based health self-management intervention in adults with chronic spinal cord injury (SCI). DESIGN: Single-blinded randomized controlled trial. SETTING: General community. PARTICIPANTS: Convenience sample of adults with SCI (N=84; mean time post-SCI, 9.9y; mean age, 46y; 73.8% men; 44% with paraplegia; 58% white). INTERVENTIONS: Trained peer health coaches applied the person-centered health self-management intervention with 42 experimental subjects over 6 months on a tapered call schedule. The 42 control subjects received usual care. Both groups received the MCMC Resource Guide. MAIN OUTCOME MEASURES: Primary outcome-health self-management as measured by the Patient Activation Measure (PAM). Secondary outcomes-global ratings of service/resource use, health-related quality of life, and quality of primary care. RESULTS: Intervention participants averaged 12 calls over 6 months (averaging 21.8min each), with distinct variation. At 6 months, intervention participants reported a significantly greater change in PAM scores (6mo: estimate, 7.029; 95% confidence interval, .1018-13.956; P=.0468) compared with controls, with a trend toward significance at 4 months. At 6 months, intervention participants reported a significantly greater decrease in social/role activity limitations (estimate, -.443; P=.0389), greater life satisfaction (estimate, 1.0091; P=.0522), greater services/resources awareness (estimate, 1.678; P=.0253), greater overall service use (estimate, 1.069; P=.0240), and a greater number of services used (estimate, 1.542; P=.0077). Subgroups most impacted by MCMC on PAM change scores included the following: high social support, white persons, men, 1 to 6 years postinjury, and tetraplegic. CONCLUSIONS: This trial demonstrates that the MCMC peer-led, health self-management intervention achieved a positive impact on self-management to prevent secondary conditions in adults with SCI. These results warrant a larger, multisite trial of its efficacy and cost-effectiveness.

Developing Artificial Neural Network Models to Predict Functioning One Year After Traumatic Spinal Cord Injury.

OBJECTIVE: To develop mathematical models for predicting level of independence with specific functional outcomes 1 year after discharge from inpatient rehabilitation for spinal cord injury. DESIGN: Statistical analyses using artificial neural networks and logistic regression. SETTING: Retrospective analysis of data from the national, multicenter Spinal Cord Injury Model Systems (SCIMS) Database. PARTICIPANTS: Subjects (N=3142; mean age, 41.5y) with traumatic spinal cord injury who contributed data for the National SCIMS Database longitudinal outcomes studies. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Self-reported ambulation ability and FIM-derived indices of level of assistance required for self-care activities (ie, bed-chair transfers, bladder and bowel management, eating, toileting). RESULTS: Models for predicting ambulation status were highly accurate (>85% case classification accuracy; areas under the receiver operating characteristic curve between .86 and .90). Models for predicting nonambulation outcomes were moderately accurate (76%-86% case classification accuracy; areas under the receiver operating characteristic curve between .70 and .82). The performance of models generated by artificial neural networks closely paralleled the performance of models analyzed using logistic regression constrained by the same independent variables. CONCLUSIONS: After further prospective validation, such predictive models may allow clinicians to use data available at the time of admission to inpatient spinal cord injury rehabilitation to accurately predict longer-term ambulation status, and whether individual patients are likely to perform various self-care activities with or without assistance from another person.

Empowering Adults With Chronic Spinal Cord Injury to Prevent Secondary Conditions.

OBJECTIVE: To develop and assess the feasibility of My Care My Call, an innovative peer-led, community-based telephone intervention for individuals with chronic spinal cord injury (SCI) using peer health coaches. DESIGN: Qualitative pilot study. SETTING: General community. PARTICIPANTS: Convenience sample of consumer advocates with traumatic SCI ≥1 year postinjury (N=7). INTERVENTIONS: My Care My Call applies a health empowerment approach for goal-setting support, education, and referral to empower consumers in managing their preventive health needs. For feasibility testing, peer health coaches, trained in brief action planning, called participants 6 times over 3 weeks. MAIN OUTCOME MEASURES: Identified focus areas were acceptability, demand, implementation, and practicality. Participant outcome data were collected through brief after-call surveys and qualitative exit interviews. Through a custom website, peer health coaches documented call attempts, content, and feedback. Analysis applied the constant comparative method. RESULTS: My Care My Call was highly feasible in each focus area for participants. Concerning acceptability, participants were highly satisfied, rating peer health coaches as very good or excellent in 80% of calls; felt My Care My Call was appropriate; and would continue use. Regarding demand, participants completed 88% of scheduled calls; reported that My Care My Call fills a real need; and would recommend it. Considering implementation, peer health coaches made 119% of expected calls, with a larger focus on compiling individualized resources. For practicality, call duration averaged 29 minutes, with 1 hour of additional time for peer health coaches. Participant effects included feeling supported, greater confidence toward goals, and greater connection to resources. Subsequently, several process changes enhanced peer health coach training and support through role-plays, regular support calls, and streamlined My Care My Call support materials. CONCLUSIONS: After process changes, a randomized controlled trial to evaluate My Care My Call is underway.

Spinal Cord Injury-Functional Index/Assistive Technology Short Forms.

OBJECTIVES: To evaluate the psychometric properties of the Spinal Cord Injury-Functional Index/Assistive Technology (SCI-FI/AT) short forms (SFs) in the domains of basic mobility, self-care, fine motor function, and ambulation based on internal consistency; correlations between SFs and full item banks, and a 10-item computerized adaptive test (CAT) version; magnitude of ceiling and floor effects; and measurement precision across a broad range of function in a sample of adults with spinal cord injury (SCI). DESIGN: Cross-sectional cohort study. SETTING: Nine national Spinal Cord Injury Model Systems programs. PARTICIPANTS: A sample of adults with traumatic SCI (N=460) stratified by level of injury (paraplegia/tetraplegia), completeness of injury, and time since SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: SCI-FI/AT full item bank, 10-item CAT, and SFs (with separate Self-Care and Fine Motor Function SFs for persons with tetraplegia and paraplegia). RESULTS: The SCI-FI/AT SFs demonstrated very good internal consistency, group-level reliability, and excellent correlations between SFs and scores based on the CAT version and the total item bank. Ceiling and floor effects are acceptable (except for unacceptable ceiling effects for persons with paraplegia on the Self-Care and Fine Motor Function SFs). The test information functions are excellent across a broad range of functioning typical of persons with paraplegia and tetraplegia. CONCLUSIONS: Clinicians and researchers should consider using the SCI-FI/AT SFs to assess functioning with the use of assistive technology when CAT applications are not available.

Temporal assessment of splenic function in patients who have undergone percutaneous image-guided splenic artery embolization in the setting of trauma.

PURPOSE: The role of transcatheter splenic arterial embolization (SAE) in the nonoperative management of splenic injury is evolving. The purpose of this study is to evaluate patients who have undergone SAE for laboratory markers of hyposplenism in the years after their procedure. MATERIALS AND METHODS: Thirty-four subjects who had undergone SAE as part of nonoperative management of splenic trauma during a period of 10 years were included. A blood sample was collected from each patient for complete blood count and smear analysis for peripheral markers of hyposplenism (as indicated by Howell-Jolly bodies [HJBs]). Sample size and power analysis was performed, and likelihoods for various true prevalences were calculated. RESULTS: The average time interval from procedure to follow-up was 4.4 years. No participants had peripheral markers of hyposplenism or abnormalities in cell count on follow-up. CONCLUSIONS: Phagocytic function of the spleen in patients who have undergone SAE is preserved, as evidenced by the absence of HJBs on follow-up peripheral blood smears.

Ultrasound-guided fascia iliaca compartment block for hip fractures in the emergency department.

BACKGROUND: Hip fracture (HFx) is a painful injury that is commonly seen in the emergency department (ED). Patients who experience pain from HFx are often treated with intravenous opiates, which may cause deleterious side effects, particularly in elderly patients. An alternative to systemic opioid analgesia involves peripheral nerve blockade. This approach may be ideally suited for the ED environment, where one injection could control pain for many hours. OBJECTIVES: We hypothesized that an ultrasound-guided fascia iliaca compartment block (UFIB) would provide analgesia for patients presenting to the ED with pain from HFx and that this procedure could be performed safely by emergency physicians (EP) after a brief training. METHODS: In this prospective, observational, feasibility study, a convenience sample of 20 cognitively intact patients with isolated HFx had a UFIB performed. Numerical pain scores, vital signs, and side effects were recorded before and after administration of the UFIB at pre-determined time points for 8h. RESULTS: All patients reported decreased pain after the nerve block, with a 76% reduction in mean pain score at 120 min. There were no procedural complications. CONCLUSION: In this small group of ED patients, UFIB provided excellent analgesia without complications and may be a useful adjunct to systemic pain control for HFx.

Detection of active gastrointestinal hemorrhage with CT angiography: a 4(1/2)-year retrospective review.

PURPOSE: To retrospectively evaluate the performance of computed tomography (CT) angiography in the detection and localization of clinically active gastrointestinal (GI) hemorrhage of an unknown source. MATERIALS AND METHODS: Eighty-six CT angiograms were obtained in 74 patients with the clinical diagnosis of acute GI hemorrhage of an unknown source. Results of CT angiography were recorded, and the patients' electronic medical records were reviewed for documentation of subsequent interventional procedures performed within 24 hours of the reference CT angiogram to diagnose or control ongoing GI hemorrhage. Surgical, endoscopic, and final pathologic reports, if available, were reviewed. RESULTS: Twenty-two of the 86 CT angiograms (26%) were positive for active hemorrhage, with findings confirmed in 19 of the 22 cases (86%). Thirteen cases were confirmed with angiography, five cases were confirmed with surgery, and one case was confirmed with autopsy. Sixty-four of the 86 CT angiograms were negative, and 59 (92%) of the CT angiograms required no further intervention. These patients were discharged without incident. There were no cases in which CT angiography was negative and subsequent angiography within 24 hours was positive. The overall sensitivity, specificity, accuracy, and positive and negative predictive value of CT angiography in the detection of active GI hemorrhage within this study population were 79%, 95%, 91%, 86%, and 92%, respectively. CONCLUSIONS: CT angiography provides valuable information that can be used to determine the appropriateness of catheter angiography and guide mesenteric catheterization if a bleeding source is localized. The authors' experience with this study cohort supports its use before angiography in those patients with acute GI bleeding of an unknown source who are being considered for catheter-directed intervention.

Neuraxial hematoma and paralysis after enoxaparin administration 3 days after attempted spinal anesthesia for total knee arthroplasty.

A 69-year-old man underwent a total knee arthroplasty. Spinal anesthesia was attempted, but when unsuccessful, a general anesthesia was given. The surgery and rehabilitation were uneventful until postoperative day 3 when a pulmonary embolism was diagnosed. He was placed on enoxaparin at a therapeutic dose that begun more than 72 hours after his attempted spinal. He developed a spinal hematoma and was paralyzed. The literature has no recommendations for using enoxaparin at therapeutic doses after regional anesthesia. There is no previous report to suggest that a patient 72 hours after surgery is still at risk from a neuraxial hematoma.

The Technological Impact of COVID-19 on the Future of Education and Health Care Delivery.

BACKGROUND: The unexpected COVID-19 crisis has disrupted medical education and patient care in unprecedented ways. Despite the challenges, the health-care system and patients have been both creative and resilient in finding robust "temporary" solutions to these challenges. It is not clear if some of these COVID-era transitional steps will be preserved in the future of medical education and telemedicine. OBJECTIVES: The goal of this commentary is to address the sometimes substantial changes in medical education, continuing medical education (CME) activities, residency and fellowship programs, specialty society meetings, and telemedicine, and to consider the value of some of these profound shifts to "business as usual" in the health-care sector. METHODS: This is a commentary is based on the limited available literature, online information, and the front-line experiences of the authors. RESULTS: COVID-19 has clearly changed residency and fellowship programs by limiting the amount of hands-on time physicians could spend with patients. Accreditation Council for Graduate Medicine Education has endorsed certain policy changes to promote greater flexibility in programs but still rigorously upholds specific standards. Technological interventions such as telemedicine visits with patients, virtual meetings with colleagues, and online interviews have been introduced, and many trainees are "techno-omnivores" who are comfortable using a variety of technology platforms and techniques. Webinars and e-learning are gaining traction now, and their use, practicality, and cost-effectiveness may make them important in the post-COVID era. CME activities have migrated increasingly to virtual events and online programs, a trend that may also continue due to its practicality and cost-effectiveness. While many medical meetings of specialty societies have been postponed or cancelled altogether, technology allows for virtual meetings that may offer versatility and time-saving opportunities for busy clinicians. It may be that future medical meetings embrace a hybrid approach of blending digital with face-to-face experience. Telemedicine was already in place prior to the COVID-19 crisis but barriers are rapidly coming down to its widespread use and patients seem to embrace this, even as health-care systems navigate the complicated issues of cybersecurity and patient privacy. Regulatory guidance may be needed to develop safe, secure, and patient-friendly telehealth applications. Telemedicine has affected the prescribing of controlled substances in which online counseling, informed consent, and follow-up must be done in a virtual setting. For example, pill counts can be done in a video call and patients can still get questions answered about their pain therapy, although it is likely that after the crisis, prescribing controlled substances may revert to face-to-face visits. LIMITATIONS: The health-care system finds itself in a very fluid situation at the time this was written and changes are still occurring and being assessed. CONCLUSIONS: Many of the technological changes imposed so abruptly on the health-care system by the COVID-19 pandemic may be positive and it may be beneficial that some of these transitions be preserved or modified as we move forward. Clinicians must be objective in assessing these changes and retaining those changes that clearly improve health-care education and patient care as we enter the COVID era.

The effects of splenic artery embolization on nonoperative management of blunt splenic injury: a 16-year experience.

INTRODUCTION: Nonoperative management (NOM) of blunt splenic injury has become the preferred treatment for hemodynamically stable patients. The application of splenic artery embolization (SAE) in NOM has been controversial. We hypothesized that incorporation of initial use of SAE into a practice protocol for patients at high risk for NOM failure (contrast extravasation or pseudoaneurysm on computed tomography, grade 3 injury with large hemoperitoneum, grade 4 injuries) would improve patient outcomes. METHODS: A retrospective analysis of three continuums of practice was performed: group I (January 1991-June 1998), SAE not part of routine NOM; group II (July 1998-December 2001), introduction and discretionary use of SAE; and group III (January 2002-June 2007), standardized use of initial SAE for patients considered at high risk of nonoperative failure. The primary outcome measure was the success of NOM. Failure of NOM was defined as the need for abdominal operation. Secondary outcomes were mortality, length of stay, and splenic salvage. RESULTS: Over 16 years, 815 patients with blunt splenic injury were treated at our level 1 trauma center. There were 222 patients in group I, 195 in group II, and 398 in group III. There was an increase in the use of SAE over time with a significant improvement in the utilization of NOM (61% in group I; 82% in group II; 88% in group III; p < 0.05). This was associated with an increase in successful NOM (77%, group I; 94%, group II; 97%, group III; p < 0.0001 group I vs. group II and III). Mortality, length of stay, and splenic salvage were similar in groups II and III but significantly improved when compared with group I. CONCLUSIONS: The increased use of initial SAE in high-risk patients expanded the successful use of NOM but was not associated with other incremental improvements.

Reducing pressure ulcer prevalence rates in the long-term acute care setting.

Information about pressure ulcer prevalence, prevention, and optimal management strategies in the long-term acute care hospital (LTACH) setting is sparse. Although care processes in other patient care settings have been reported to affect pressure ulcer prevalence rates, the effect of such programs in the LTACH is unknown. To reduce perceived above-average pressure ulcer prevalence rates and improve care processes, a 108-bed LTACH used a failure mode and effects analysis to identify and address high-priority areas for improvement. Areas in need of improvement included a lack of 1) wound care professionals, 2) methods to consistently document prevention and wound data, and 3) an interdisciplinary wound care team approach, as well as a faulty electronic medical record. While prevalence data were collected, policies and procedures based on several published guidelines were developed and incorporated into the pressure ulcer plan of care by the newly established wound care team. Improved assessment and documentation methods, enhanced staff education, revised electronic records, wound care product reviews, and a facility-wide commitment to improved care resulted in a reduction of facility-acquired pressure ulcer prevalence from 41% at baseline to an average of 4.2% during the following 12 months as well as fewer missing electronic record data (<1% of charts had missing data). These study results suggest that staff education, better documentation, and a dedicated wound care team improves care practices and reduces pressure ulcer prevalence in the LTACH. Studies to increase knowledge about the LTACH patient population and their unique needs and risk profiles are needed.

Acute gastrointestinal bleeding: emerging role of multidetector CT angiography and review of current imaging techniques.

Acute gastrointestinal bleeding is a common cause of hospitalization, morbidity, and mortality in the United States. The evaluation and treatment of acute gastrointestinal bleeding are complex and often require a multispecialty approach involving gastroenterologists, surgeons, internists, emergency physicians, and radiologists. The multitude of pathologic processes that can result in gastrointestinal bleeding, the length of the gastrointestinal tract, and the often intermittent nature of gastrointestinal bleeding further complicate patient evaluation. In addition, there are multiple imaging modalities and therapeutic interventions that are currently being used in the evaluation and treatment of acute gastrointestinal hemorrhage, each with its own strengths and weaknesses. Initial experience indicates that multidetector computed tomographic angiography is a promising first-line modality for the time-efficient, sensitive, and accurate diagnosis or exclusion of active gastrointestinal hemorrhage and may have a profound impact on the evaluation and subsequent treatment of patients who present with acute gastrointestinal bleeding.

Arterial embolus during common iliac balloon catheterization at cesarean hysterectomy.

BACKGROUND: Placenta accreta is associated with significant maternal morbidity. Prophylactic iliac artery balloon placement has been described as a treatment adjunct to minimize maternal risk of excessive blood loss at hysterectomy. CASE: A 37-year-old multigravida presented at 37 weeks of gestation with a known placenta previa and suspected placenta accreta. Iliac artery balloon catheters were placed immediately before cesarean delivery. The balloons were inflated after the infant was delivered, and placental-site hemorrhage required a cesarean hysterectomy with a 1,500-mL blood loss. A left popliteal arterial thrombus diagnosed postoperatively required thromboembolectomy. The patient was discharged home on postoperative day 5 with no further sequelae. CONCLUSION: Prophylactic arterial balloon occlusion may be associated with risks unique to pregnant women.

Bottom-feeding for blockbuster businesses.

Marketing experts tell companies to analyze their customer portfolios and weed out buyer segments that don't generate attractive returns. Loyalty experts stress the need to aim retention programs at "good" customers--profitable ones- and encourage the "bad" ones to buy from competitors. And customer-relationship-management software provides ever more sophisticated ways to identify and eliminate poorly performing customers. On the surface, the movement to banish unprofitable customers seems reasonable. But writing off a customer relationship simply because it is currently unprofitable is at best rash and at worst counterproductive. Executives shouldn't be asking themselves, How can we shun unprofitable customers? They need to ask, How can we make money off the customers that everyone else is shunning? When you look at apparently unattractive segments through this lens, you often see opportunities to serve those segments in ways that fundamentally change customer economics. Consider Paychex, a payroll-processing company that built a nearly billion-dollar business by serving small companies. Established players had ignored these customers on the assumption that small companies couldn't afford the service. When founder Tom Golisano couldn't convince his bosses at Electronic Accounting Systems that they were missing a major opportunity, he started a company that now serves 390,000 U.S. customers, each employing around 14 people. In this article, the authors look closely at bottom-feeders--companies that assessed the needs of supposedly unattractive customers and redesigned their business models to turn a profit by fulfilling those needs. And they offer lessons other executives can use to do the same.

Cryoablation vs. radiofrequency ablation for small renal masses.

RATIONALE AND OBJECTIVES: Cancer of the kidney is the third most common cancer of the urinary tract, and renal cell carcinoma is the most lethal of all genitourinary tumors. The incidental discovery of renal cell carcinoma has increased with increased use of cross-sectional imaging. Concomitantly, minimally invasive ablative technologies, including image-guided cryoablation, radiofrequency ablation, and others, have evolved as therapeutic options for small renal masses. MATERIALS AND METHODS: Between 2006 and 2009, 111 patients (age range, 31-91 years; mean age, 70 years) underwent percutaneous computed tomography-guided thermal ablation for suspected renal cell carcinoma at two major academic centers. Outcomes data were retrospectively collected and analyzed to compare recurrence rates for patients undergoing radiofrequency ablation (n = 41) versus cryoablation (n = 70). RESULTS: There were four cases of suspicious enhancement on follow-up computed tomography or magnetic resonance imaging in each group, with cumulative imaging recurrence rates of 11% and 7% for radiofrequency ablation and cryoablation, respectively. Log rank test analysis revealed no significant difference between rates of imaging recurrence between the two groups (P = .6044). CONCLUSIONS: These results suggest that the use of cryoablative technology will result in similar outcomes compared with radiofrequency ablation.