Treatment of severe traumatic brain injury with human bone marrow mesenchymal stem cell extracellular vesicles: a case report.

Objective: Extracellular vesicles (EVs) derived from regenerative mesenchymal stem cells might safely treat traumatic brain injury (TBI). We evaluated the safety and efficacy of a human bone marrow derived mesenchymal stem cell EVs (hBM-MSC EV) investigational product (IP) in a patient with severe TBI.

Design: A single case study employing an IP with a strong safety profile in over 200 patients.

Effects of a novel GABA-B positive allosteric modulator, ASP8062, on alcohol cue-elicited craving and naturalistic alcohol consumption in a multisite randomized, double-blind, placebo-controlled trial.

Background: The γ-aminobutyric acid-B (GABA) receptor is a promising target for the development of new medications to treat alcohol use disorder (AUD). The GABA agonist baclofen has been reported to reduce alcohol consumption but is associated with some undesirable side effects, including sedation. ASP8062 is a novel compound that acts as a positive allosteric modulator at the GABA receptor and may be more tolerable than baclofen.

Complementary, integrative, and standard rehabilitative therapies in a military population with chronic predominantly musculoskeletal pain: a pragmatic clinical trial with SMART design.

There is growing acceptance for combining complementary and integrative health (CIH) therapies with standard rehabilitative care (SRC) for chronic pain management, yet little evidence on the best sequence of therapies. We investigated whether starting with CIH therapies or SRC is more effective in reducing pain impact. Participants were 280 service members with predominantly (88%) musculoskeletal chronic pain referred to an interdisciplinary pain management center who were randomized to a twice weekly program of either CIH therapies (n = 140) or SRC (n = 140) for the 3-week first stage of treatment.

Fatigue and Sleep-related Impairment as Predictors of the Effect of Nonpharmacological Therapies for Active duty Service Members With Chronic Pain: A Secondary Analysis of a Pragmatic Randomized Clinical Trial.

Introduction: First-line treatments for chronic pain include selected complementary and integrative health therapies, including spinal manipulation, acupuncture, yoga, and massage; and standard rehabilitative care, including physical and occupational therapies. This study aimed to uncover critical factors that contribute to pain impact and the effectiveness of complementary and integrative health therapies and standard rehabilitative care among people with chronic pain, with a focus on the role of sleep-related impairment.

Materials And Methods: We conducted a secondary analysis of data from a pragmatic randomized clinical trial of 280 U.

Epidemiology and outcome of medical emergency team calls within 48 hours of intensive care unit discharge.

Background: Some patients experience early (within 48 h) clinical deterioration and medical emergency team (MET) review following intensive care unit (ICU) discharge. Few studies have explored early MET review, despite it being a recognised quality and safety indicator.

Aims: To evaluate the (i) proportion of patients discharged from ICU receiving MET review and timing of reviews; (ii) characteristics of patients who received early MET review and (iii) predictors of early MET review and associations with clinical outcomes.

Bone marrow mesenchymal stem cell-derived extracellular vesicle infusion for amyotrophic lateral sclerosis.

In this pilot safety study, we hypothesized that a human bone marrow stem cell-derived extracellular vesicle (hBM-MSC EV) investigational product (IP) would be safe and exhibit potential efficacy in amyotrophic lateral sclerosis (ALS) patients. Ten ALS patients received two 10-ml intravenous infusions of the IP given 1 month apart and evaluated over 3 months. There were no serious adverse events or adverse events related to the IP and 30% of subjects' ALS functional rating scale-revised (ALSFRS-R) scores did not decline.

Relationship Between Treatment Hours of Selected Disciplines And Change in Pain Impact During the Year Following Referral to an Interdisciplinary Pain Management Center: A Latent Class Analysis.

Pain management clinics differ in treatments offered, and little evidence exists regarding which combinations of therapies result in best outcomes. This study analyzed clinical encounters and pain outcomes data for associations between treatment composition and outcomes. Retrospective observational study of 2,142 predominantly active-duty US service members referred to an interdisciplinary pain management center between 2014 and 2021.

A novel extracellular vesicle paradigm for the treatment of COVID-19 induced acute respiratory distress syndrome (ARDS).

Efficacy of mesenchymal stem cells (MSCs) for treatment of acute respiratory distress syndrome (ARDS) suggests bioactive bone marrow MSC extracellular vesicles (BM-MSC EVs) may be effective. A patient with severe COVID-19 associated ARDS who was presumed to expire was treated with a BM-MSC EV preparation (14 doses over two months) as a rescue treatment for refractory COVID ARDS. Near complete reversal of lung inflammation and fibrosis (per computed tomography), near complete restoration of mobility, hospital discharge (3 months) with resumption of normal activities of daily living (one year) and return to work occurred.

Role of Pain Catastrophizing in the Effects of Cognitive Behavioral Therapy for Chronic Pain in Different Subgroups: An Exploratory Secondary Data Analysis Using Finite Mixture Models.

Introduction: Providing effective treatment for debilitating chronic pain is a challenge among many populations including military service members. Cognitive behavioral therapy for chronic pain (CBT-CP) is a leading psychological pain treatment. Pain catastrophizing is a pivotal mediator of pain-related outcomes.

Safety of bone marrow derived mesenchymal stem cell extracellular vesicle injection for lumbar facet joint pain.

A 3-month pilot study to evaluate the safety of injecting a bone marrow-derived mesenchymal stem cell extracellular vesicle advanced investigational product (IP) into the lumbar facet joint space as a treatment for chronic low back pain. 20 healthy adults were treated with IP injections (0.5 ml/joint) and evaluated by three functional assessments 1, 3, 7, 14, 30, 60 and 90 days later.

Safety and Efficacy of Intravenous ExoFlo in the Treatment of Complex Regional Pain Syndrome.

Background: Complex regional pain syndrome (CRPS) is an extremely painful disorder driven primarily by inflammation.

Objectives: We hypothesized that the immunomodulatory biologic, ExoFloTM, composed of bone marrow mesenchymal stem cell-derived extracellular vesicles, could be safely administered to CRPS patients and alleviate symptoms.

Study Design: Ten patients received 2 intravenous (IV) infusions, each containing 15 mL ExoFlo, on day one and day 4.

Pain Catastrophizing and Its Association with Military Medical Disability Among US Active Duty Service Members with Chronic Predominately Musculoskeletal Pain: A Retrospective Cohort Analysis.

Context: Pain catastrophizing is characterized by negative emotional and cognitive responses to pain and is a predictor of work-related disability. Its association with military medical disability has not been studied.

Objective: To (1) identify the pain catastrophizing scale (PCS) score cut point most strongly associated with military medical disability, (2) measure the difference in rate of disability between service members with baseline PCS scores above versus below the cut point, and (3) determine if improvement in PCS score during pain specialty care is associated with decreased likelihood of disability.

Standardizing Evidence-Based Practice Review Processes Across the Defense Health Agency Enterprise.

Background: The Defense Health Agency (DHA) Campaign Plan identifies Ready Reliable Care (RRC) as one of the eight strategic initiatives. A critical aspect of RRC is standardizing evidence-based practice (EBP) across Military Health System to include training, technology, equipment, and processes. The TriService Nursing Research Program hosted an EBP Summit to address this expectation.

Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure: The ARIES-HM3 Randomized Clinical Trial.

Importance: Left ventricular assist devices (LVADs) enhance quality and duration of life in advanced heart failure. The burden of nonsurgical bleeding events is a leading morbidity. Aspirin as an antiplatelet agent is mandated along with vitamin K antagonists (VKAs) with continuous-flow LVADs without conclusive evidence of efficacy and safety.

Predictors of Sustained Response to Functional Restoration in a Military Population.

Introduction: The purpose of this study was to determine if improvement in pain impact and functional performance following a functional restoration (FR) program was sustained up to 6 months posttreatment and to identify predictors of sustained improvement.

Materials And Methods: Secondary analysis of data collected during randomized clinical trial. Study population included 108 US active duty service members who completed an FR program, as well as 3- and/or 6-month follow-up assessments.

A network analysis of pain intensity and pain-related measures of physical, emotional, and social functioning in US military service members with chronic pain.

Objective: The purpose of this study was to apply network analysis methodology to better understand the relationships between pain-related measures among people with chronic pain.

Methods: We analyzed data from a cross-sectional sample of 4614 active duty service members with chronic pain referred to 1 military interdisciplinary pain management center between 2014 and 2021. Using a combination of Patient-Reported Outcomes Measurement Information System measures and other pain-related measures, we applied the "EBICglasso" algorithm to create regularized partial correlation networks that would identify the most influential measures.

BMAL1 loss in oligodendroglia contributes to abnormal myelination and sleep.

Myelination depends on the maintenance of oligodendrocytes that arise from oligodendrocyte precursor cells (OPCs). We show that OPC-specific proliferation, morphology, and BMAL1 are time-of-day dependent. Knockout of Bmal1 in mouse OPCs during development disrupts the expression of genes associated with circadian rhythms, proliferation, density, morphology, and migration, leading to changes in OPC dynamics in a spatiotemporal manner.

Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicle Infusion for the Treatment of Respiratory Failure From COVID-19: A Randomized, Placebo-Controlled Dosing Clinical Trial.

Background: Bone marrow mesenchymal stem cell (BM-MSC)-derived extracellular vesicles (ExoFlo) convey the immunomodulatory and regenerative properties of intact BM-MSCs. This study aimed to determine the safety and efficacy of ExoFlo as treatment for moderate to severe ARDS in patients with severe COVID-19.

Research Question: Do two doses of ExoFlo safely reduce mortality in COVID-19-associated moderate to severe ARDS compared with placebo?

Study Design And Methods: A prospective phase 2 multicenter double-anonymized randomized placebo-controlled dosing trial was conducted at five sites across the United States with infusions of placebo, 10 mL of ExoFlo, or 15 mL of ExoFlo on days 1 and 4.

Association of Angiopoetin-2 and TNF-α With Bleeding During Left Ventricular Assist Device Support: Analysis From the PREVENT Biorepository.

The purpose of this study was to describe the changes in plasma levels of angiogenic and inflammatory biomarkers, specifically Ang-2 and TNF-α, in patients receiving HeartMate II (HMII) left ventricular assist device (LVAD) and correlate them with nonsurgical bleeding. It has been shown that angiopoietin-2 (Ang-2) and tissue necrosis factor-α (TNF-α) may be linked to bleeding in LVAD patients. This study utilized biobanked samples prospectively collected from the PREVENT study, a prospective, multicenter, single-arm, nonrandomized study of patients implanted with HMII.

Evaluation of a diagnostic device, CL Detect rapid test for the diagnosis of new world cutaneous leishmaniasis in Peru.

Background: Cutaneous leishmaniasis (CL) is a neglected disease and a public health problem in Latin America. The diagnosis of CL in poor hyperendemic regions relies to large extent on the identification of amastigotes in Giemsa-stained smears. There is an urgent need for a rapid, sensitive and low cost diagnostic method for use in field conditions for CL as current modalities are not readily available.

Enhanced Thrombin Formation in Patients With Ventricular Assist Devices Experiencing Bleeding: Insights From the Multicenter PREVENT Study.

The aim of this investigation was to characterize the hemostatic status of heart failure patients with implanted left ventricular assist devices (LVADs) to propose a mechanism associated with bleeding. Patients (n = 300) from 23 US hospitals were enrolled in the PREVENtion of HeartMate II Pump Thrombosis through Clinical Management (PREVENT) study. A biobank was established with serum and plasma samples prospectively collected from a cohort of 175 patients preimplant baseline (BL) and 3 months (3M) postimplant.

The Influence of Time and Place on the Experiences of US Military Nurses in Vietnam.

Background: Although the conflict in Vietnam (usually referred to as the Vietnam War) ended almost 50 years ago, few research-based publications of nurses' experiences in Vietnam exist.

Purpose: The purpose of this study was to expand what is known about the experiences of US military nurses who served in Vietnam.

Methods: This secondary analysis used qualitative description to examine interview data from 15 nurses who served in-country (within Vietnam) and in-theater supporting Vietnam (e.

Increase of Bacterial Leaf Streak in Hard Red Spring Wheat in North Dakota and Yield Loss Considerations.

Bacterial leaf streak (BLS), caused by pv. , has increased in both prevalence and severity in the major hard red spring wheat (HRSW)-producing state North Dakota. The disease is readily observed after flag leaf emergence and can quickly lead to defoliation and severe yield loss.