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Randomized phase 2b dose-escalation trial of stem cell therapy with laromestrocel for aging frailty
No full textFrailty, a syndrome that decreases healthspan in older individuals, lacks effective therapies. We conducted a randomized, dose-finding clinical trial to test whether human bone marrow-derived allogeneic mesenchymal stem cells (MSCs; laromestrocel) improve physical functioning and patient self-reported outcomes in ambulatory individuals with frailty (ClinicalTrials.gov #NCT03169231; N = 148). Laromestrocel infusion results in clinically meaningful, dose- and time-dependent increases in the 6-min walk test (6MWT; primary endpoint) compared with placebo: 63.4 m (95% confidence interval [CI]: 17.1-109.6 m; p = 0.0077) at month 9 and 41.3 m (95% CI: -2.4-84.9 m; p = 0.0635) at month 6. Increased 6MWT distance correlates with PROMIS Physical Function score, and increasing doses of laromestrocel are associated with decreases in soluble (degraded) tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (TIE2), the cognate receptor for the angiopoietins, identifying a potential biomarker of laromestrocel responsiveness. These findings identify a stem cell therapy approach for the management of patients with hypomobility and other features of aging frailty
Tele-delivered psychotherapeutic intervention for family members of patients in intensive care-a non-randomized pilot study
No full textFamily members of patients in intensive care units (ICU) experience psychological distress both during and after the ICU stay. Yet, past interventions are few and largely ineffective.
We developed a flexible, tele-delivered psychotherapeutic intervention based on contemporary cognitive therapeutic methods and tested its feasibility in a one-arm pilot study. Although evaluated in family members of patients with COVID-19, the intervention was developed to be broadly applicable to mental health problems in ICU family caregivers.
Adult family members of patients with COVID-19 in five ICUs across Denmark received weekly sessions with clinical psychologists during the ICU stay and on a needs basis for eight weeks post-discharge. The intervention manual specified a catalog of treatment principles and methods from contemporary cognitive therapies. Questionnaires evaluating peritraumatic distress, anxiety, depression, stress, rumination, worry, and tolerance of uncertainty were administered at pre-intervention, post-intervention, six-, and twelve-month follow-up. Mixed-effects models estimated the change in mental health symptoms over time. A subset of family members and psychologists completed in-depth interviews post-intervention analyzed with thematic analysis.
Of 43 eligible family members, 40 (93%) participated. Two withdrew consent during the intervention. On average, family members received 6 sessions (range: 0-15) over 9 to 118 days. Both the tele-delivery format and the intervention methods were found feasible and acceptable by family members as well as psychologists, and family members found the intervention beneficial in validating and addressing their evolving needs and helping them manage distress. Preliminary effects at post-intervention were large reductions in mental health symptoms for peritraumatic distress (Hedges' g = -0.86, 95% confidence interval (CI) = [-1.2 to -0.25]), anxiety (g = -2.46, [-2.36 to -1.51]), and depression (g = -1.77, [-2.5 to -0.88]), also seen at follow-up, together with medium improvements for perceived stress.
This tele-based psychotherapeutic intervention for family members of patients in ICUs was feasible and acceptable, and tele-delivered contemporary cognitive therapies present a promising approach for reducing peritraumatic distress, anxiety, and depression.
Clinicaltrials.gov (NCT04409821)
Palliative Care Education for Pediatric Critical Care Trainees: A Scoping Review and a Call to Action
No full textObjective Review the current teaching methods, curricula, and assessment tools for pediatric palliative care (PPC) within the pediatric s intensive care setting for pediatric critical care medicine (PCCM) trainees as it pertains to the following domains: (1) Symptom management, (2) Communication, (3) Spiritual/Psychosocial, (4) End of Life (EOL).Data Sources PubMed, Cochrane CENTRAL, EMBASE, and PsycINFO were searched for articles reporting on PPC educational curricula or interventions for residents and fellows in pediatric intensive care settings. The search strategy used a combination of MeSH terms and keywords to search for items that addressed intensive care, pediatrics, palliative care, residents or fellows, and education.Study Selection Curricula that includes PCCM trainees (fellows and residents) nationally and internationally.Data Extraction Covidence.Data Synthesis Of 105 articles reviewed, 6 articles addressed PPC education in the PICU between 2015 and 2025. All 6 articles were United States-based and included simulation curricula focused on communication regarding EOL care. Evaluation tools varied across articles. There is a paucity of data around complex symptom management, communication on topics other than EOL, and spiritual and psychosocial education.Conclusions Simulation focused on communication and EOL care is frequently used to teach PPC knowledge and skills to PCCM fellows and residents. Currently varied evaluation methods exist with limited PPC domains. This review highlights the need for future PPC curricula development for PCCM trainees
Strengthening peer support for families bereaved by sudden unexpected infant death: Development and evaluation of a standardized training course
No full textSudden Unexpected Infant Death (SUID) is the leading cause of postneonatal mortality worldwide. Bereaved parents commonly seek peer support for bereavement-related needs, but competencies and standardized training for organizations offering peer facilitators are lacking. We developed and piloted a train-the-trainer curriculum addressing peer facilitators' knowledge, skills, and attitudes for supporting SUID-bereaved parents. A needs assessment of international peer support organizations and expert consensus from an international working group informed development of competencies and a curriculum. A 1.5-day in-person pilot of eight participants from five countries was conducted, followed by remote sessions. Pre- and post-training surveys assessed impact. Wilcoxon signed-rank tests analyzed outcomes; open-ended responses were de .05) were shown across 13 competencies, including grief literacy and group facilitation skills, suggesting the curriculum is feasible, acceptable, and effective. This train-the-trainer model may support scalable, global peer bereavement training
Barriers to the Adoption of Healthy Lifestyle Behaviors in Patients With Cancer: Results of a National Survey
No full textHealthy lifestyle behaviors, including regular exercise and balanced nutrition, affect quality of life in cancer survivors. However, barriers to adopting these behaviors across the cancer continuum are poorly understood. We evaluated barriers to adopting healthy lifestyle behaviors in a national cohort of patients and survivors of cancer.
ASCO distributed an online survey to adult patients with cancer in the United States from March to June 2020. In this secondary analysis, we evaluated the perceived barriers to incorporating healthy lifestyle behaviors after cancer diagnosis and how they differ by disease stage and treatment status. Descriptive statistics summarized barriers to lifestyle changes. Comparisons across disease stage and treatment status were assessed using Rao-Scott chi-square tests, and weighted multivariable logistic regression modeling identified associated factors.
Of 2,419 survey respondents, 1,987 were included in this analysis and grouped by disease stage: early stage on-treatment (n = 461), early stage post-treatment (n = 916), and metastatic on-treatment (n = 610). The most common barriers to healthy behaviors included lack of energy (58.7%) and physical limitations (52.0%), with significant differences (
< .05) in barriers related to time, logistics, cancer effects, and physical limitations across disease stages and treatment groups. Among those not meeting lifestyle guidelines, lack of motivation (51.3%-62.0%) and lack of energy (59.5%-77.0%) were major barriers, with barriers related to time, cancer effects, and physical limitations varying significantly by disease stage and treatment status.
Patients with cancer face multiple barriers to adopting healthy lifestyle behaviors after diagnosis. Targeted interventions based on disease stage and treatment status may help address these challenges
Changes in Tarsal Tunnel Volume and Pressure After Minimally Invasive Lateral Sliding Calcaneal Osteotomy: A Cadaveric Study
No full textAcantholytic disorders: Update on pathophysiology, diagnosis, and management
No full textAcantholytic skin disorders without a primary immunological etiology are characterized by impaired intercellular adhesion between epidermal keratinocytes. Genetic acantholytic disorders include Darier disease (DD) and Hailey-Hailey disease (HHD); the pathogenesis of Grover disease (GD) is unknown. Since these conditions are not commonly seen in clinical practice, diagnoses may be missed and there are no standardized guidelines to direct treatment. Topical steroids and retinoids are typically utilized for mild disease, and oral retinoids, particularly acitretin, have often been used for more severe disease, but efficacy is not universal. There is emerging evidence for biologics and small molecular inhibitors, including dupilumab, tumor necrosis factor-α inhibitors, apremilast, and Janus kinase (JAK) inhibitors to treat refractory disease. Recent data and personal experience suggest potential efficacy of low-dose naltrexone as monotherapy or adjunctive treatment. Overactivity of the interleukin-17/23 and interleukin 4/13 axes or MAPK/ERK pathways may point to novel therapeutic strategies, including guselkumab. Direct SERCA activators may hold potential for treatment of DD. This clinical review aims to equip physicians to diagnose acantholytic disorders and provide expert treatment recommendations based on emerging evidence
Temperature-activated dislocation avalanches signaling brittle-to-ductile transition in BCC micropillars
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We carry out strain-controlled in-situ compression experiments of micron-sized tungsten (W) micropillars in the temperature range 300–900 K, together with simulations of three-dimensional discrete dislocation dynamics (DDD) at the same scale. Two distinct regimes are observed. At low temperatures, plastic deformation appears smooth, both temporally and spatially. Stress fluctuations are consistent with a Wiener stochastic process resulting from uncorrelated dislocation activity within the pillars. However, high-temperature stress fluctuations are highly correlated and exhibit features of self-organized criticality (SOC), with deformation located within well-defined slip bands. The high-temperature stress relaxation statistics are consistent with a thermally activated nucleation process from the surface. The nature of the transition between the two regimes is a manifestation of the brittle to ductile transition in BCC metals
Propagation of orbitalization metrics in vacuum
No full textThe degree of orbitalization O was recently proposed [J. Opt. 27, 065606 (2025)] for a scalar beam carrying L OAM modes, as a quantitative measure of the weight of the fully orbitalized state within the total beam — analogously to the degree of polarization used for vector beams. In this work, we extend the framework by introducing two additional degrees: the degree of partial orbitalization P and the degree of unorbitalization U, quantifying the relative contributions of orbital states arising from coupling of 2 to L−1 modes, and all L modes, respectively. We then examine, in detail, the evolution of all three degrees in vacuum through numerical examples based on three beam classes, each differing in the number and coupling properties of their OAM modes. Our results show that, unlike the degree of polarization, which can be readily controlled anywhere within the beam from the source plane, the orbitalization measures exhibit rigid transverse distributions that remain structurally invariant upon propagation and retain constant values at their extrema. This robust behavior could prove useful for remote sensing and communications with structured light.•Random OAM-carrying beams are quantified by three orbitalization degrees.•The metrics give the radial power in pure, partially and totally mixed OAM states.•For fixed radii the three metrics rebalance, with the sum remaining unity.•The metrics remain structurally invariant in vacuum - they only diffract with range.•The metrics can be used for quality analysis and robust information transfer